PMID- 26989583 TI - Maximum Likelihood and Restricted Likelihood Solutions in Multiple-Method Studies. AB - A formulation of the problem of combining data from several sources is discussed in terms of random effects models. The unknown measurement precision is assumed not to be the same for all methods. We investigate maximum likelihood solutions in this model. By representing the likelihood equations as simultaneous polynomial equations, the exact form of the Groebner basis for their stationary points is derived when there are two methods. A parametrization of these solutions which allows their comparison is suggested. A numerical method for solving likelihood equations is outlined, and an alternative to the maximum likelihood method, the restricted maximum likelihood, is studied. In the situation when methods variances are considered to be known an upper bound on the between-method variance is obtained. The relationship between likelihood equations and moment-type equations is also discussed. PMID- 26989585 TI - Geometric Effects When Measuring Small Holes With Micro Contact Probes. AB - A coordinate measuring machine with a suitably small probe can be used to measure micro-features such as the diameter and form of small holes (often about 100 MUm in diameter). When measuring small holes, the clearance between the probe tip and the part is sometimes nearly as small as other characteristic lengths (such as probe deflection or form errors) associated with the measurement. Under these circumstances, the basic geometry of the measurement is much different than it is for the measurement of a macroscopic object. Various geometric errors are greatly magnified, and consequently sources of error that are totally irrelevant when measuring macroscopic artifacts can become important. In this article we discuss errors associated with misalignment or non-orthogonality of the probe axes, probe tip radius compensation, and mechanical filtering. PMID- 26989584 TI - The SIM Time Network. AB - The Sistema Interamericano de Metrologia (SIM) is a regional metrology organization (RMO) whose members are the national metrology institutes (NMIs) located in the 34 nations of the Organization of American States (OAS). The SIM/OAS region extends throughout North, Central, and South America and the Caribbean Islands. About half of the SIM NMIs maintain national standards of time and frequency and must participate in international comparisons in order to establish metrological traceability to the International System (SI) of units. The SIM time network (SIMTN) was developed as a practical, cost effective, and technically sound way to automate these comparisons. The SIMTN continuously compares the time standards of SIM NMIs and produces measurement results in near real-time by utilizing the Internet and the Global Positioning System (GPS). Fifteen SIM NMIs have joined the network as of December 2010. This paper provides a brief overview of SIM and a technical description of the SIMTN. It presents international comparison results and examines the measurement uncertainties. It also discusses the metrological benefits that the network provides to its participants. PMID- 26989586 TI - The Role of Lattice Matching Techniques in the Characterization of Polymorphic Forms. AB - An inspection of the recent literature reveals that polymorphism is a frequently encountered phenomenon. The recognition of polymorphic forms plays a vital role in the materials sciences because such structures are characterized by different crystal packing and accordingly have different physical properties. In the pharmaceutical industry, recognition of polymorphic forms can be critical for, in certain cases, a polymorphic form of a drug may be an ineffective therapeutic agent due to its unfavorable physical properties. A check of the recent literature has revealed that in some cases new polymorphic forms are not recognized. In other instances, a supposedly new polymeric form is actually the result of an incorrect structure determination. Fortunately, lattice-matching techniques, which have proved invaluable in the identification and characterization of crystal structures, represent a powerful tool for analyzing polymorphic forms. These lattice-matching methods are based on either of two strategies: (a) the reduced cell strategy-the matching of reduced cells of the respective lattices or (b) the matrix strategy-the determination of a matrix or matrices relating the two lattices coupled with an analysis of the matrix elements. Herein, these techniques are applied to three typical cases-(a) the identification of a new polymorphic form, (b) the demonstration that a substance may not be a new polymorphic form due to missed symmetry, and (c) the evaluation of pseudo polymorphism because of a missed lattice. To identify new polymorphic forms and to prevent errors, it is recommended that these lattice matching techniques become an integral part of the editorial review process of crystallography journals. PMID- 26989587 TI - Re-Optimized Energy Levels and Ritz Wavelengths of (198)Hg I. AB - The procedure of level optimization for the (198)Hg I spectrum emitted by electrodeless discharge lamps is revisited. Wavelength-measurement uncertainties and systematic shifts caused by interactions with the buffer gas and by calibration procedures are carefully analyzed and accounted for. Based on this extended analysis of the original measurements, the energy levels are re optimized, which results in an improved set of level values consistent with the revised measured wavelengths. The newly obtained reliable Ritz wavelengths can be used as secondary wavelength standards in the wide range from 1200 A to 65 000 A. PMID- 26989588 TI - Best Practice Guidelines for Pre-Launch Characterization and Calibration of Instruments for Passive Optical Remote Sensing. AB - The pre-launch characterization and calibration of remote sensing instruments should be planned and carried out in conjunction with their design and development to meet the mission requirements. The onboard calibrators such as blackbodies and the sensors such as spectral radiometers should be characterized and calibrated using SI traceable standards. In the case of earth remote sensing, this allows inter-comparison and intercalibration of different sensors in space to create global time series of climate records of high accuracy where some inevitable data gaps can be easily bridged. The recommended best practice guidelines for this pre-launch effort is presented based on experience gained at National Institute of Standards and Technology (NIST), National Aeronautics and Space Administration (NASA) and National Oceanic and Atmospheric Administration (NOAA) programs over the past two decades. The currently available radiometric standards and calibration facilities at NIST serving the remote sensing community are described. Examples of best practice calibrations and intercomparisons to build SI (international System of Units) traceable uncertainty budget in the instrumentation used for preflight satellite sensor calibration and validation are presented. PMID- 26989589 TI - Selecting Valid Correlation Areas for Automated Bullet Identification System Based on Striation Detection. AB - Some automated bullet identification systems calculate a correlation score between two land impressions to measure their similarity. When extracting a compressed profile from the land impression of a fired bullet, inclusion of areas that do not contain valid individual striation information may lead to sub optimal extraction and therefore may deteriorate the correlation result. In this paper, an edge detection algorithm and selection process are used together to locate the edge points of all tool-mark features and filter out those not corresponding to striation marks. Edge points of the resulting striation marks are reserved and expanded to generate a mask image. By imposing the mask image on the topography image, the weakly striated area(s) are removed from the expressed profile extraction. Using this method, 48 bullets fired from 12 gun barrels of six manufacturers resulted in a higher matching rate than previous studies. PMID- 26989590 TI - Electromagnetic Metrology on Concrete and Corrosion. AB - To augment current methods for the evaluation of reinforcing bar (rebar) corrosion within concrete, we are exploring unique features in the dielectric and magnetic spectra of pure iron oxides and corrosion samples. Any signature needs to be both prominent and consistent in order to identify corrosion within concrete bridge deck or other structures. In order to measure the permittivity and propagation loss through concrete as a function of temperature and humidity, we cut and carefully fitted samples from residential concrete into three different waveguides. We also poured and cured a mortar sample within a waveguide that was later measured after curing 30 days. These measurements were performed from 45 MHz to 12 GHz. Our concrete measurements showed that the coarse granite aggregate that occupied about half the sample volume reduced the electromagnetic propagation loss in comparison to mortar. We also packed ground corrosion samples and commercially available iron-oxide powders into a transmission-line waveguide and found that magnetite and corrosion sample spectra are similar, with a feature between 0.5 GHz and 2 GHz that may prove useful for quantifying corrosion. We also performed reflection (S 11) measurements at various corrosion surfaces and in loose powders from 45 MHz to 50 GHz. These results are a first step towards quantifying rebar corrosion in concrete. PMID- 26989591 TI - Development of Multicolor Flow Cytometry Calibration Standards: Assignment of Equivalent Reference Fluorophores (ERF) Unit. AB - A procedure is described for assigning the number of equivalent reference fluorophores (ERF) values to microspheres labeled with a fluorophore designed to produce a fluorescence response in a given fluorescence channel of a multicolor flow cytometer. A fluorimeter was calibrated by a series of solutions of the reference fluorophores. The fluorimeter was used to obtain the microsphere fluorescence intensity, and a multicolor flow cytometer was used to obtain the microsphere concentration. The microsphere fluorescence intensity and the concentration were used to obtain the value of ERF for each model microsphere calibration standard. The procedure is described in detail only for microspheres with allophycocyanin (APC) immobilized on the surface. ERF values were also determined for microsphere calibrators for three other fluorescence channels: fluorescein isothiocyanate (FITC), phycoerythrin (PE), and Pacific Blue(PB). The four model microsphere calibrators provide a one point calibration for the four channels of a flow cytometer. By using software controls and changing the photomultiplier voltages, it is possible to obtain a multipoint calibration for each fluorescence channel using each microsphere calibrator. PMID- 26989592 TI - RECIST Applied to Realistic Tumor Models. AB - RECIST (Response Evaluation Criteria in Solid Tumors) is a linear measure intended to predict tumor size in medical computed tomography (CT). In this work, using purely geometrical considerations, we estimate how well RECIST can predict the volume of randomly-oriented tumor models, each composed of the union of ellipsoids. The principal conclusion is that RECIST is likely to work less well for realistic tumors than for ellipsoids. PMID- 26989593 TI - Vacuum Technology Considerations For Mass Metrology. AB - Vacuum weighing of mass artifacts eliminates the necessity of air buoyancy correction and its contribution to the measurement uncertainty. Vacuum weighing is also an important process in the experiments currently underway for the redefinition of the SI mass unit, the kilogram. Creating the optimum vacuum environment for mass metrology requires careful design and selection of construction materials, plumbing components, pumping, and pressure gauging technologies. We review the vacuum technology(1) required for mass metrology and suggest procedures and hardware for successful and reproducible operation. PMID- 26989594 TI - Atomic Force Microscope Cantilever Flexural Stiffness Calibration: Toward a Standard Traceable Method. AB - The evolution of the atomic force microscope into a useful tool for measuring mechanical properties of surfaces at the nanoscale has spurred the need for more precise and accurate methods for calibrating the spring constants of test cantilevers. Groups within international standards organizations such as the International Organization for Standardization and the Versailles Project on Advanced Materials and Standards (VAMAS) are conducting studies to determine which methods are best suited for these calibrations and to try to improve the reproducibility and accuracy of these measurements among different laboratories. This paper expands on a recent mini round robin within VAMAS Technical Working Area 29 to measure the spring constant of a single batch of triangular silicon nitride cantilevers sent to three international collaborators. Calibration techniques included reference cantilever, added mass, and two forms of thermal methods. Results are compared to measurements traceable to the International System of Units provided by an electrostatic force balance. A series of guidelines are also discussed for procedures that can improve the running of round robins in atomic force microscopy. PMID- 26989595 TI - Improved First-Principles Calculation of the Third Virial Coefficient of Helium. AB - We employ state-of-the-art pair and three-body potentials with path-integral Monte Carlo (PIMC) methods to calculate the third density virial coefficient C(T) for helium. The uncertainties are much smaller than those of the best experimental results, and approximately one-fourth the uncertainty of our previous work. We have extended our results in temperature down to 2.6 K, incorporating the effect of spin statistics that become important below approximately 7 K. Results are given for both the (3)He and (4)He isotopes. We have also performed PIMC calculations of the third acoustic virial coefficient gamma a; our calculated values compare well with the limited experimental data available. A correlating equation for C(T) of (4)He is presented; differentiation of this equation provides a reliable and simpler way of calculating gamma a. PMID- 26989596 TI - Effect of Calcium Hydroxide on the Fracture Resistance of Dentin. AB - An increased incidence of fracture has been reported in teeth where root canals were treated with calcium hydroxide. Edge chipping is one test used to measure the resistance of brittle materials to fracture. Presently, no studies have reported on edge chipping in teeth. This study evaluated the fracture resistance of human dentin exposed to calcium hydroxide for up to 60 days using the edge chipping method. Twelve recently extracted teeth were divided into a control group and three experimental groups with varying calcium hydroxide exposures. All teeth underwent pulpectomy via standard protocol. It was expected that the edge chip resistance would decrease as a function of exposure, but the results showed the converse. Chip resistance may reflect both the fracture resistance and the hardness of dentin, a quasi brittle material. PMID- 26989597 TI - The Use of Filtered Radiometers for Radiance Measurement. AB - A methodology for using a calibrated filter radiometer to measure and monitor the spectral radiance of calibration sources is described. An example is presented using the NIST calibration sphere source that is used to support the NASA Earth Observing remote-sensing program. PMID- 26989598 TI - New Measurement Service for Determining Pressure Sensitivity of Type LS2aP Microphones by the Reciprocity Method. AB - A new National Institute of Standards and Technology (NIST) measurement service has been developed for determining the pressure sensitivities of American National Standards Institute and International Electrotechnical Commission type LS2aP laboratory standard microphones over the frequency range 31.5 Hz to 20 000 Hz. At most frequencies common to the new service and the old service, the values of the expanded uncertainties of the new service are one-half the corresponding values of the old service, or better. The new service uses an improved version of the system employed by NIST in the Consultative Committee for Acoustics, Ultrasound, and Vibration (CCAUV) key comparison CCAUV.A-K3. Measurements are performed using a long and a short air-filled plane-wave coupler. For each frequency in the range 31.5 Hz to 2000 Hz, the reported sensitivity level is the average of data from both couplers. For each frequency above 2000 Hz, the reported sensitivity level is determined with data from the short coupler only. For proof test data in the frequency range 31.5 Hz to 2000 Hz, the average absolute differences between data from the long and the short couplers are much smaller than the expanded uncertainties. PMID- 26989599 TI - Comparison of Two Dimension-Reduction Methods for Network Simulation Models. AB - Experimenters characterize the behavior of simulation models for data communications networks by measuring multiple responses under selected parameter combinations. The resulting multivariate data may include redundant responses reflecting aspects of a smaller number of underlying behaviors. Reducing the dimension of multivariate responses can reveal the most significant model behaviors, allowing subsequent analyses to focus on one response per behavior. This paper investigates two methods for reducing dimension in multivariate data generated from simulation models. One method combines correlation analysis and clustering. The second method uses principal components analysis. We apply both methods to reduce a 22-dimensional dataset generated by a network simulator. We identify issues that an analyst must decide, and we compare the reductions suggested by the methods. We have used these methods to identify significant behaviors in simulated networks, and we suspect they may be applied to reduce the dimension of empirical data measured from real networks. PMID- 26989600 TI - The Current SI Seen From the Perspective of the Proposed New SI. AB - A revised International System of Units (SI) proposed by the International Committee for Weights and Measures is under consideration by the General Conference on Weights and Measures for eventual adoption. Widely recognized as a significant advance for both metrology and science, it is defined via statements that explicitly fix the numerical values of a selected set of seven reference constants when the values of these constants are expressed in certain specified units. At first sight this approach to defining a system of units appears to be quite different from that used to define the current SI. However, by showing how the definitions of the seven base units of the current SI also fix the numerical values of a set of seven reference constants (broadly interpreted) when the values of these constants are expressed in their coherent SI units, and how the definition of the current SI can be recast into the same form as that of the revised SI under consideration, we show that the revision is not as radical a departure from the current SI as it might initially seem. PMID- 26989601 TI - Combining Results From Multiple Evaluations of the Same Measurand. AB - According to the Guide to the Expression of Uncertainty in Measurement (GUM), a result of measurement consists of a measured value together with its associated standard uncertainty. The measured value and the standard uncertainty are interpreted as the expected value and the standard deviation of a state-of knowledge probability distribution attributed to the measurand. We discuss the term metrological compatibility introduced by the International Vocabulary of Metrology, third edition (VIM3) for lack of significant differences between two or more results of measurement for the same measurand. Sometimes a combined result of measurement from multiple evaluations of the same measurand is needed. We propose an approach for determining a combined result which is metrologically compatible with the contributing results. PMID- 26989602 TI - Long-Term Stability of the NIST Conical Reference Transducer. AB - The National Institute of Standards and Technology (NIST) Conical Reference Transducer (CRT) is designed for purposes requiring frequency response characteristics much more uniform than those attainable with ultrasonic transducers conventionally used for acoustic emission (AE) nondestructive testing. The high performance of the CRT results from the use of design elements radically different from those of conventional transducers. The CRT was offered for sale for 15 years (1985 to 2000). Each CRT was furnished with data which expressed, as a function of frequency, the transducer sensitivity in volts per micrometer of normal displacement on the test block. Of the 22 transducers constructed, eight were reserved for long term research and were stored undisturbed in a laboratory with well controlled temperature and humidity. In 2009, the sensitivities of these eight units were redetermined. The 2009 data have been compared with data from similar tests conducted in 1985. The results of this comparison verify the claim "Results of tests of the long term stability of CRT characteristics indicate that, if proper care is taken, tens of years of service can reasonably be expected." made in the CRT specifications document furnished to prospective customers. PMID- 26989603 TI - Microhotplate Temperature Sensor Calibration and BIST. AB - In this paper we describe a novel long-term microhotplate temperature sensor calibration technique suitable for Built-In Self Test (BIST). The microhotplate thermal resistance (thermal efficiency) and the thermal voltage from an integrated platinum-rhodium thermocouple were calibrated against a freshly calibrated four-wire polysilicon microhotplate-heater temperature sensor (heater) that is not stable over long periods of time when exposed to higher temperatures. To stress the microhotplate, its temperature was raised to around 400 degrees C and held there for days. The heater was then recalibrated as a temperature sensor, and microhotplate temperature measurements were made based on the fresh calibration of the heater, the first calibration of the heater, the microhotplate thermal resistance, and the thermocouple voltage. This procedure was repeated 10 times over a period of 80 days. The results show that the heater calibration drifted substantially during the period of the test while the microhotplate thermal resistance and the thermocouple-voltage remained stable to within about plus or minus 1 degrees C over the same period. Therefore, the combination of a microhotplate heater-temperature sensor and either the microhotplate thermal resistance or an integrated thin film platinum-rhodium thermocouple can be used to provide a stable, calibrated, microhotplate-temperature sensor, and the combination of the three sensor is suitable for implementing BIST functionality. Alternatively, if a stable microhotplate-heater temperature sensor is available, such as a properly annealed platinum heater-temperature sensor, then the thermal resistance of the microhotplate and the electrical resistance of the platinum heater will be sufficient to implement BIST. It is also shown that aluminum- and polysilicon-based temperature sensors, which are not stable enough for measuring high microhotplate temperatures (>220 degrees C) without impractically frequent recalibration, can be used to measure the silicon substrate temperature if never exposed to temperatures above about 220 degrees C. PMID- 26989605 TI - Racial Differences Affecting Night Time Blood Pressure Dipping Groups in Hypertensive Patients. AB - BACKGROUND: Normal blood pressure (BP) follows a circadian rhythm, with dipping of BP at night. However, little has been done to show how the dipping groups vary amongst the White and Asian population at different periods of the year. This study aims to examine the pattern of nocturnal dipping between the White and Asian population, as well as to compare it to the different timings of the year, between summer and winter. METHODS: Ambulatory Blood Pressure Monitor recordings were obtained from 220 patients, half were White patients obtained from Mercy University Hospital, Cork, Ireland and half were Asian patients from National Heart Centre, Singapore during the summer period from May to June and the winter period from October to December. RESULTS: Both the Irish and Singaporeans exhibit a decrease in total number of reverse dipper from summer to winter. However, the redistribution of reverse dipper was mainly to the dippers in Singapore, while in Ireland it was to both the extreme dipper and dipper. Irish seasonal changes also resulted in an increase in nocturnal diastolic pressure (95% CI, 0.72 to 6.03, 3.37 mm Hg; p<0.05) and a change in the duration of dipping at night (95% CI, 0.045 to 1.01, 0.53 Hours; p<0.05). CONCLUSION: Regardless of race or temperature, reverse dippers seem to decrease in winter. However, the racial differences dictate the redistribution of the fall in number of dippers. This has implications on how reverse dippers should be treated at different periods of the year. PMID- 26989604 TI - Findings and Recommendations From the Joint NIST-AGA Workshop on Odor Masking. AB - Since the days of the alchemist, the observation that some substances have a smell while other substances do not has been a source of fascination. The sense of smell, or olfaction, is our least understood sense, however it is important for many human functions, including digestion, food selection and hazard avoidance. The detailed explanation of why individual chemicals (called odorants) might have a particular smell is still elusive. The situation with mixtures of odorants is even more complex and interesting. A number of distinct odorant mixture phenomena have been documented. Odorant suppression (sometimes called masking), conjugation (as described first by Zwaadermaker) and cross-adaptation are among a collection of such phenomena. They are related to the differential effects that one odorant species will have when mixed with another. Masking is a term that describes situations in which one odorant can overpower the sensation of another. There may be profound technological implications in a number of industrial sectors, most prominently in the fuel gas sector. Here, masking is suspected when the odorant that is added to natural gas can be detected by analytical instrumentation, but cannot be properly detected by an observer with a normal sense of smell. Note that this phenomenon is distinct from odor fade, which more properly describes a decrease in the concentration of an odorant rather than a decrease, disappearance or qualitative change in the perception of the odor in the absence of a change in absolute concentration. Anecdotal descriptions of masking events in the natural gas industry have persisted for over a decade, with the frequency of such events on the rise. Pursuant to the philosophy that the technological problem cannot be addressed until the basic science is understood, NIST, in collaboration with the American Gas Association (AGA), sponsored a workshop that brought together olfactory scientists and natural gas operations personnel in an effort to achieve a common understanding and identify critical research questions. This document is a summary of that workshop, and most importantly, a compendium of the findings and recommendations that resulted from the meeting. PMID- 26989606 TI - Prevalence of asymptomatic urinary tract infections in morbidly obese dogs. AB - Background. Obesity has reached epidemic proportions in dogs and, as in humans, cost of care has increased due to associated comorbidities. In humans, asymptomatic urinary tract infections (UTI) may be more prevalent in the obese. Asymptomatic bacteriuria (AB) is the term used when UTI are asymptomatic. We hypothesized that morbidly obese dogs are similarly more likely to have asymptomatic bacteriuria than lean, overweight, and moderately obese dogs. Methods. A retrospective study was undertaken to explore a possible association between obesity and asymptomatic bacteriuria. Records from lean, overweight, and obese dogs receiving both a dual energy absorptiometry (DXA) scan and urine culture were included. Results. Six positive urine cultures were identified among 46 dogs fulfilling search criteria. All six positive cultures were found in dogs with body fat percentage of >45%. In dogs with body fat percentage of <45%, there were no positive urine cultures. Discussion. There was an increased prevalence of asymptomatic bacteriuria in the morbidly obese dogs in this study compared to those that were lean, overweight, or moderately obese. Whether antibiotic therapy is necessary in such cases is still being debated, but because asymptomatic bacteriuria may be associated with ascending infections, uroliths, or other complications, the data reported herein support the screening of obese patients for bacteriuria. PMID- 26989607 TI - Computational inference of H3K4me3 and H3K27ac domain length. AB - Background. Recent epigenomic studies have shown that the length of a DNA region covered by an epigenetic mark is not just a byproduct of the assaying technologies and has functional implications for that locus. For example, expanded regions of DNA sequences that are marked by enhancer-specific histone modifications, such as acetylation of histone H3 lysine 27 (H3K27ac) domains coincide with cell-specific enhancers, known as super or stretch enhancers. Similarly, promoters of genes critical for cell-specific functions are marked by expanded H3K4me3 domains in the cognate cell type, and these can span DNA regions from 4-5kb up to 40-50kb in length. These expanded H3K4me3 domains are known as buffer domains or super promoters. Methods. To ask what correlates with-and potentially regulates-the length of loci marked with these two important histone marks, H3K4me3 and H3K27ac, we built Random Forest regression models. With these models, we computationally identified genomic and epigenomic patterns that are predictive for the length of these marks in seven ENCODE cell lines. Results. We found that certain epigenetic marks and transcription factors explain the variability of the length of H3K4me3 and H3K27ac marks across different cell types, which implies that the lengths of these two epigenetic marks are tightly regulated in a given cell type. Our source code for the regression models and data can be found at our GitHub page: https://github.com/zubekj/broad_peaks. Discussion. Our Random Forest based regression models enabled us to estimate the individual contribution of different epigenetic marks and protein binding patterns to the length of H3K4me3 and H3K27ac deposition patterns, therefore potentially revealing genomic signatures at cell specific regulatory elements. PMID- 26989608 TI - Effects of glucose, ethanol and acetic acid on regulation of ADH2 gene from Lachancea fermentati. AB - Background. Not all yeast alcohol dehydrogenase 2 (ADH2) are repressed by glucose, as reported in Saccharomyces cerevisiae. Pichia stipitis ADH2 is regulated by oxygen instead of glucose, whereas Kluyveromyces marxianus ADH2 is regulated by neither glucose nor ethanol. For this reason, ADH2 regulation of yeasts may be species dependent, leading to a different type of expression and fermentation efficiency. Lachancea fermentati is a highly efficient ethanol producer, fast-growing cells and adapted to fermentation-related stresses such as ethanol and organic acid, but the metabolic information regarding the regulation of glucose and ethanol production is still lacking. Methods. Our investigation started with the stimulation of ADH2 activity from S. cerevisiae and L. fermentati by glucose and ethanol induction in a glucose-repressed medium. The study also embarked on the retrospective analysis of ADH2 genomic and protein level through direct sequencing and sites identification. Based on the sequence generated, we demonstrated ADH2 gene expression highlighting the conserved NAD(P) binding domain in the context of glucose fermentation and ethanol production. Results. An increase of ADH2 activity was observed in starved L. fermentati (LfeADH2) and S. cerevisiae (SceADH2) in response to 2% (w/v) glucose induction. These suggest that in the presence of glucose, ADH2 activity was activated instead of being repressed. An induction of 0.5% (v/v) ethanol also increased LfeADH2 activity, promoting ethanol resistance, whereas accumulating acetic acid at a later stage of fermentation stimulated ADH2 activity and enhanced glucose consumption rates. The lack in upper stream activating sequence (UAS) and TATA elements hindered the possibility of Adr1 binding to LfeADH2. Transcription factors such as SP1 and RAP1 observed in LfeADH2 sequence have been implicated in the regulation of many genes including ADH2. In glucose fermentation, L. fermentati exhibited a bell-shaped ADH2 expression, showing the highest expression when glucose was depleted and ethanol-acetic acid was increased. Meanwhile, S. cerevisiae showed a constitutive ADH2 expression throughout the fermentation process. Discussion. ADH2 expression in L. fermentati may be subjected to changes in the presence of non-fermentative carbon source. The nucleotide sequence showed that ADH2 transcription could be influenced by other transcription genes of glycolysis oriented due to the lack of specific activation sites for Adr1. Our study suggests that if Adr1 is not capable of promoting LfeADH2 activation, the transcription can be controlled by Rap1 and Sp1 due to their inherent roles. Therefore in future, it is interesting to observe ADH2 gene being highly regulated by these potential transcription factors and functioned as a promoter for yeast under high volume of ethanol and organic acids. PMID- 26989609 TI - Adverse events associated with incretin-based drugs in Japanese spontaneous reports: a mixed effects logistic regression model. AB - BACKGROUND: Spontaneous Reporting Systems (SRSs) are passive systems composed of reports of suspected Adverse Drug Events (ADEs), and are used for Pharmacovigilance (PhV), namely, drug safety surveillance. Exploration of analytical methodologies to enhance SRS-based discovery will contribute to more effective PhV. In this study, we proposed a statistical modeling approach for SRS data to address heterogeneity by a reporting time point. Furthermore, we applied this approach to analyze ADEs of incretin-based drugs such as DPP-4 inhibitors and GLP-1 receptor agonists, which are widely used to treat type 2 diabetes. METHODS: SRS data were obtained from the Japanese Adverse Drug Event Report (JADER) database. Reported adverse events were classified according to the MedDRA High Level Terms (HLTs). A mixed effects logistic regression model was used to analyze the occurrence of each HLT. The model treated DPP-4 inhibitors, GLP-1 receptor agonists, hypoglycemic drugs, concomitant suspected drugs, age, and sex as fixed effects, while the quarterly period of reporting was treated as a random effect. Before application of the model, Fisher's exact tests were performed for all drug-HLT combinations. Mixed effects logistic regressions were performed for the HLTs that were found to be associated with incretin-based drugs. Statistical significance was determined by a two-sided p-value <0.01 or a 99% two-sided confidence interval. Finally, the models with and without the random effect were compared based on Akaike's Information Criteria (AIC), in which a model with a smaller AIC was considered satisfactory. RESULTS: The analysis included 187,181 cases reported from January 2010 to March 2015. It showed that 33 HLTs, including pancreatic, gastrointestinal, and cholecystic events, were significantly associated with DPP-4 inhibitors or GLP-1 receptor agonists. In the AIC comparison, half of the HLTs reported with incretin-based drugs favored the random effect, whereas HLTs reported frequently tended to favor the mixed model. CONCLUSION: The model with the random effect was appropriate for analyzing frequently reported ADEs; however, further exploration is required to improve the model. The core concept of the model is to introduce a random effect of time. Modeling the random effect of time is widely applicable to various SRS data and will improve future SRS data analyses. PMID- 26989610 TI - A quantitative look on northwestern Tethyan foraminiferal assemblages, Campanian Nierental Formation, Austria. AB - Deposits spanning the Radotruncana calcarata Taxon Range Zone at the Postalm section, Northern Calcareous Alps (Austria) are examined quantitatively for foraminiferal assemblages, especially the planktonic group. This study focuses on establishing a high resolution record spanning an 800 ka long stratigraphic interval from the active continental margin of the Penninic Ocean. The Postalm section displays reddish limestone- marl alternations representing precession cycles. For this study, 26 samples were taken bed by bed to allow a "per precession-cycle" resolution (i.e., a minimum sample distance of ~20 ka). Samples from limestones as well as from marls were examined for foraminiferal assemblages. Data suggest a typical, open marine Campanian foraminiferal community. The >63 um fraction is dominated by opportunist taxa, i.e., members of Muricohedbergella and biserial planktic foraminifera. Archaeoglobigerina and "Globigerinelloides" appear frequently and benthic foraminifera are very sparsely found. The share of globotruncanids, representing more complex morphotypes amongst planktonic foraminifera, is recorded with 5-10%. The state of preservation of foraminifera from the Postalm section is moderate to poor. Differences between samples from marls and samples from limestone are evident, but do not reveal evidence that there was an influence on the postdepositional microfossil communities. However, data from microfossils showing moderate to bad preservation can still offer valuable insight into the palaeoenvironment and biostratigraphy. Information gathered on the composition of the planktonic foraminiferal assemblage confirms a low-to-mid-latitude setting for the Postalm section. As well resolved records of Late Cretaceous foraminifera assemblages are rare, the examination of the Radotruncana calcarata Taxon Range Zone provides some insights into variations and short term changes during the very short period of 800 ka. PMID- 26989611 TI - Diuron tolerance and potential degradation by pelagic microbiomes in the Great Barrier Reef lagoon. AB - Diuron is a herbicide commonly used in agricultural areas where excess application causes it to leach into rivers, reach sensitive marine environments like the Great Barrier Reef (GBR) lagoon and pose risks to marine life. To investigate the impact of diuron on whole prokaryotic communities that underpin the marine food web and are integral to coral reef health, GBR lagoon water was incubated with diuron at environmentally-relevant concentration (8 ug/L), and sequenced at specific time points over the following year. 16S rRNA gene amplicon profiling revealed no significant short- or long-term effect of diuron on microbiome structure. The relative abundance of prokaryotic phototrophs was not significantly altered by diuron, which suggests that they were largely tolerant at this concentration. Assembly of a metagenome derived from waters sampled at a similar location in the GBR lagoon did not reveal the presence of mutations in the cyanobacterial photosystem that could explain diuron tolerance. However, resident phages displayed several variants of this gene and could potentially play a role in tolerance acquisition. Slow biodegradation of diuron was reported in the incubation flasks, but no correlation with the relative abundance of heterotrophs was evident. Analysis of metagenomic reads supports the hypothesis that previously uncharacterized hydrolases carried by low-abundance species may mediate herbicide degradation in the GBR lagoon. Overall, this study offers evidence that pelagic phototrophs of the GBR lagoon may be more tolerant of diuron than other tropical organisms, and that heterotrophs in the microbial seed bank may have the potential to degrade diuron and alleviate local anthropogenic stresses to inshore GBR ecosystems. PMID- 26989612 TI - Epithelial, metabolic and innate immunity transcriptomic signatures differentiating the rumen from other sheep and mammalian gastrointestinal tract tissues. AB - Background. Ruminants are successful herbivorous mammals, in part due to their specialized forestomachs, the rumen complex, which facilitates the conversion of feed to soluble nutrients by micro-organisms. Is the rumen complex a modified stomach expressing new epithelial (cornification) and metabolic programs, or a specialised stratified epithelium that has acquired new metabolic activities, potentially similar to those of the colon? How has the presence of the rumen affected other sections of the gastrointestinal tract (GIT) of ruminants compared to non-ruminants? Methods. Transcriptome data from 11 tissues covering the sheep GIT, two stratified epithelial and two control tissues, was analysed using principal components to cluster tissues based on gene expression profile similarity. Expression profiles of genes along the sheep GIT were used to generate a network to identify genes enriched for expression in different compartments of the GIT. The data from sheep was compared to similar data sets from two non-ruminants, pigs (closely related) and humans (more distantly related). Results. The rumen transcriptome clustered with the skin and tonsil, but not the GIT transcriptomes, driven by genes from the epidermal differentiation complex, and genes encoding stratified epithelium keratins and innate immunity proteins. By analysing all of the gene expression profiles across tissues together 16 major clusters were identified. The strongest of these, and consistent with the high turnover rate of the GIT, showed a marked enrichment of cell cycle process genes (P = 1.4 E-46), across the whole GIT, relative to liver and muscle, with highest expression in the caecum followed by colon and rumen. The expression patterns of several membrane transporters (chloride, zinc, nucleosides, amino acids, fatty acids, cholesterol and bile acids) along the GIT was very similar in sheep, pig and humans. In contrast, short chain fatty acid uptake and metabolism appeared to be different between the species and different between the rumen and colon in sheep. The importance of nitrogen and iodine recycling in sheep was highlighted by the highly preferential expression of SLC14A1-urea (rumen), RHBG-ammonia (intestines) and SLC5A5-iodine (abomasum). The gene encoding a poorly characterized member of the maltase-glucoamylase family (MGAM2), predicted to play a role in the degradation of starch or glycogen, was highly expressed in the small and large intestines. Discussion. The rumen appears to be a specialised stratified cornified epithelium, probably derived from the oesophagus, which has gained some liver-like and other specialized metabolic functions, but probably not by expression of pre-existing colon metabolic programs. Changes in gene transcription downstream of the rumen also appear have occurred as a consequence of the evolution of the rumen and its effect on nutrient composition flowing down the GIT. PMID- 26989613 TI - The miRNA biogenesis in marine bivalves. AB - Small non-coding RNAs include powerful regulators of gene expression, transposon mobility and virus activity. Among the various categories, mature microRNAs (miRNAs) guide the translational repression and decay of several targeted mRNAs. The biogenesis of miRNAs depends on few gene products, essentially conserved from basal to higher metazoans, whose protein domains allow specific interactions with dsRNA. Here, we report the identification of key genes responsible of the miRNA biogenesis in 32 bivalves, with particular attention to the aquaculture species Mytilus galloprovincialis and Crassostrea gigas. In detail, we have identified and phylogenetically compared eight evolutionary conserved proteins: DROSHA, DGCR8, EXP5, RAN, DICER TARBP2, AGO and PIWI. In mussels, we recognized several other proteins participating in the miRNA biogenesis or in the subsequent RNA silencing. According to digital expression analysis, these genes display low and not inducible expression levels in adult mussels and oysters whereas they are considerably expressed during development. As miRNAs play an important role also in the antiviral responses, knowledge on their production and regulative effects can shed light on essential molecular processes and provide new hints for disease prevention in bivalves. PMID- 26989615 TI - Analyzing the proximity to cover in a landscape of fear: a new approach applied to fine-scale habitat use by rabbits facing feral cat predation on Kerguelen archipelago. AB - Although proximity to cover has been routinely considered as an explanatory variable in studies investigating prey behavioral adjustments to predation pressure, the way it shapes risk perception still remains equivocal. This paradox arises from both the ambivalent nature of cover as potentially both obstructive and protective, making its impact on risk perception complex and context dependent, and from the choice of the proxy used to measure proximity to cover in the field, which leads to an incomplete picture of the landscape of fear experienced by the prey. Here, we study a simple predator-prey-habitat system, i.e., rabbits Oryctolagus cuniculus facing feral cat Felis catus predation on Kerguelen archipelago. We assess how cover shapes risk perception in prey and develop an easily implementable field method to improve the estimation of proximity to cover. In contrast to protocols considering the "distance to nearest cover", we focus on the overall "area to cover". We show that fine-scale habitat use by rabbits is clearly related to our measure, in accordance with our hypothesis of higher risk in patches with smaller area to cover in this predator prey-habitat system. In contrast, classical measures of proximity to cover are not retained in the best predictive models of habitat use. The use of this new approach, together with a more in-depth consideration of contrasting properties of cover, could help to better understand the role of this complex yet decisive parameter for predator-prey ecology. PMID- 26989614 TI - Dynamic gene expression profiles during postnatal development of porcine subcutaneous adipose. AB - A better understanding of the control of lipogenesis is of critical importance for both human and animal physiology. This requires a better knowledge of the changes of gene expression during the process of adipose tissue development. Thus, the objective of the current study was to determine the effects of development on subcutaneous adipose tissue gene expression in growing and adult pigs. Here, we present a comprehensive investigation of mRNA transcriptomes in porcine subcutaneous adipose tissue across four developmental stages using digital gene expression profiling. We identified 3,274 differential expressed genes associated with oxidative stress, immune processes, apoptosis, energy metabolism, insulin stimulus, cell cycle, angiogenesis and translation. A set of universally abundant genes (ATP8, COX2, COX3, ND1, ND2, SCD and TUBA1B) was found across all four developmental stages. This set of genes may play important roles in lipogenesis and development. We also identified development-related gene expression patterns that are linked to the different adipose phenotypes. We showed that genes enriched in significantly up-regulated profiles were associated with phosphorylation and angiogenesis. In contrast, genes enriched in significantly down-regulated profiles were related to cell cycle and cytoskeleton organization, suggesting an important role for these biological processes in adipose growth and development. These results provide a resource for studying adipose development and promote the pig as a model organism for researching the development of human obesity, as well as being used in the pig industry. PMID- 26989616 TI - Microgeographic variation in locomotor traits among lizards in a human-built environment. AB - Microgeographic variation in fitness-relevant traits may be more common than previously appreciated. The fitness of many vertebrates is directly related to their locomotor capacity, a whole-organism trait integrating behavior, morphology, and physiology. Because locomotion is inextricably related to context, I hypothesized that it might vary with habitat structure in a wide ranging lizard, Podarcis erhardii, found in the Greek Cyclade Islands. I compared lizard populations living on human-built rock walls, a novel habitat with complex vertical structure, with nearby lizard populations that are naive to human-built infrastructure and live in flat, loose-substrate habitat. I tested for differences in morphology, behavior, and performance. Lizards from built sites were larger and had significantly (and relatively) longer forelimbs and hindlimbs. The differences in hindlimb morphology were especially pronounced for distal components-the foot and longest toe. These morphologies facilitated a significant behavioral shift in jumping propensity across a rocky experimental substrate. I found no difference in maximum velocity between these populations; however, females originating from wall sites potentially accelerated faster over the rocky experimental substrate. The variation between these closely neighboring populations suggests that the lizards inhabiting walls have experienced a suite of trait changes enabling them to take advantage of the novel habitat structure created by humans. PMID- 26989617 TI - Comparative transcriptome analysis of papilla and skin in the sea cucumber, Apostichopus japonicus. AB - Papilla and skin are two important organs of the sea cucumber. Both tissues have ectodermic origin, but they are morphologically and functionally very different. In the present study, we performed comparative transcriptome analysis of the papilla and skin from the sea cucumber (Apostichopus japonicus) in order to identify and characterize gene expression profiles by using RNA-Seq technology. We generated 30.6 and 36.4 million clean reads from the papilla and skin and de novo assembled in 156,501 transcripts. The Gene Ontology (GO) analysis indicated that cell part, metabolic process and catalytic activity were the most abundant GO category in cell component, biological process and molecular funcation, respectively. Comparative transcriptome analysis between the papilla and skin allowed the identification of 1,059 differentially expressed genes, of which 739 genes were expressed at higher levels in papilla, while 320 were expressed at higher levels in skin. In addition, 236 differentially expressed unigenes were not annotated with any database, 160 of which were apparently expressed at higher levels in papilla, 76 were expressed at higher levels in skin. We identified a total of 288 papilla-specific genes, 171 skin-specific genes and 600 co-expressed genes. Also, 40 genes in papilla-specific were not annotated with any database, 2 in skin-specific. Development-related genes were also enriched, such as fibroblast growth factor, transforming growth factor-beta, collagen-alpha2 and Integrin-alpha2, which may be related to the formation of the papilla and skin in sea cucumber. Further pathway analysis identified ten KEGG pathways that were differently enriched between the papilla and skin. The findings on expression profiles between two key organs of the sea cucumber should be valuable to reveal molecular mechanisms involved in the development of organs that are related but with morphological differences in the sea cucumber. PMID- 26989618 TI - Growth and fatty acid characterization of microalgae isolated from municipal waste-treatment systems and the potential role of algal-associated bacteria in feedstock production. AB - Much research has focused on growing microalgae for biofuel feedstock, yet there remain concerns about the feasibility of freshwater feedstock systems. To reduce cost and improve environmental sustainability, an ideal microalgal feedstock system would be fed by municipal, agricultural or industrial wastewater as a main source of water and nutrients. Nonetheless, the microalgae must also be tolerant of fluctuating wastewater quality, while still producing adequate biomass and lipid yields. To address this problem, our study focused on isolating and characterizing microalgal strains from three municipal wastewater treatment systems (two activated sludge and one aerated-stabilization basin systems) for their potential use in biofuel feedstock production. Most of the 19 isolates from wastewater grew faster than two culture collection strains under mixotrophic conditions, particularly with glucose. The fastest growing wastewater strains included the genera Chlorella and Dictyochloris. The fastest growing microalgal strains were not necessarily the best lipid producers. Under photoautotrophic and mixotrophic growth conditions, single strains of Chlorella and Scenedesmus each produced the highest lipid yields, including those most relevant to biodiesel production. A comparison of axenic and non-axenic versions of wastewater strains showed a notable effect of commensal bacteria on fatty acid composition. Strains grown with bacteria tended to produce relatively equal proportions of saturated and unsaturated fatty acids, which is an ideal lipid blend for biodiesel production. These results not only show the potential for using microalgae isolated from wastewater for growth in wastewater-fed feedstock systems, but also the important role that commensal bacteria may have in impacting the fatty acid profiles of microalgal feedstock. PMID- 26989619 TI - Response diversity of free-floating plants to nutrient stoichiometry and temperature: growth and resting body formation. AB - Free-floating plants, like most groups of aquatic primary producers, can become nuisance vegetation under certain conditions. On the other hand, there is substantial optimism for the applied uses of free-floating plants, such as wastewater treatment, biofuel production, and aquaculture. Therefore, understanding the species-specific responses of floating plants to abiotic conditions will inform both management decisions and the beneficial applications of these plants. I measured the responses of three floating plant species common in the northeast United States (Lemna minor, Spirodela polyrhiza, and Wolffia brasiliensis) to nutrient stoichiometry (nitrogen and phosphorus) and temperature in the laboratory. I also used survey data to determine the pattern of species richness of floating plants in the field and its relationship with the dominance of this group. Floating plant species exhibited unique responses to nutrient stoichiometry and temperature in the laboratory, especially under low temperatures (18 degrees C) and low nutrient conditions (0.5 mg N L(-1), 0.083 mg P L(-1)). The three species displayed an apparent tradeoff with different strategies of growth or dormancy. In the field, water bodies with three or more species of floating plants were not more frequently dominated by this group. The response diversity observed in the lab may not be associated with the dominance of this group in the field because it is masked by environmental variability, has a weak effect, or is only important during transient circumstances. Future research to develop applied uses of floating plants should examine response diversity across a greater range of species or clones and environmental conditions. PMID- 26989620 TI - H2-saturation of high affinity H2-oxidizing bacteria alters the ecological niche of soil microorganisms unevenly among taxonomic groups. AB - Soil microbial communities are continuously exposed to H2 diffusing into the soil from the atmosphere. N2-fixing nodules represent a peculiar microniche in soil where H2 can reach concentrations up to 20,000 fold higher than in the global atmosphere (0.530 ppmv). In this study, we investigated the impact of H2 exposure on soil bacterial community structure using dynamic microcosm chambers simulating soil H2 exposure from the atmosphere and N2-fixing nodules. Biphasic kinetic parameters governing H2 oxidation activity in soil changed drastically upon elevated H2 exposure, corresponding to a slight but significant decay of high affinity H2-oxidizing bacteria population, accompanied by an enrichment or activation of microorganisms displaying low-affinity for H2. In contrast to previous studies that unveiled limited response by a few species, the relative abundance of 958 bacterial ribotypes distributed among various taxonomic groups, rather than a few distinct taxa, was influenced by H2 exposure. Furthermore, correlation networks showed important alterations of ribotype covariation in response to H2 exposure, suggesting that H2 affects microbe-microbe interactions in soil. Taken together, our results demonstrate that H2-rich environments exert a direct influence on soil H2-oxidizing bacteria in addition to indirect effects on other members of the bacterial communities. PMID- 26989621 TI - An exploration of key issues and potential solutions that impact physician wellbeing and professional fulfillment at an academic center. AB - Background. Physician wellness is a vital element of a well-functioning health care system. Not only is physician wellness empirically associated with quality and patient outcomes, but its ramifications span individual, interpersonal, organizational, and societal levels. The purpose of this study was to explore academic physicians' perceptions about their work-related wellness, including the following questions: (a) What are the workplace barriers and facilitators to their wellness? (b) What workplace solutions do theythinkwouldimprove their wellness? (c)What motivates their work? and (d) What existing wellness programs are they aware of? Methods. A multi-method design was applied to conduct a total of 19 focus group sessions in 17 clinical departments. All academic faculty ranks and career lines were represented in the 64 participating physicians, who began the sessions with five open-ended survey questions pertaining to physician wellness in their work environment. Participants entered their answers into a web based survey program that enabled anonymous data collection. The initial survey component was followed by semi-structured focus group discussion. Data analysis of this qualitative study was informed by the general inductive approach as well as a review of extant literature through September 2015 on physician wellness, professional fulfillment, satisfaction, dissatisfaction, burnout and work-life. Results. Factors intrinsic to the work of physicians dominated the expressed reasons for work motivation. These factors all related to the theme of overall contribution, with categories of meaningful work, patient care, teaching, scientific discovery, self-motivation and matching of career interests. Extrinsic factors such as perceptions of suboptimal goal alignment, inadequate support, restricted autonomy, lack of appreciation, and suboptimal compensation and benefits dominated the risk of professional dissatisfaction. Discussion. Our findings indicate that the factors that enhance professional fulfillment and those that precipitate burnout are distinct: motivation and quality of work performed were supported by domains intrinsic to the work itself, whereas external dysfunctional work aspects resulted in frustration. Thus, it can be anticipated that optimization of physician wellness would require tailored approaches in each of these dimensions with sustained funding and support for wellness initiatives. Physicians identified the availability of resources to enable them to thrive and provide excellent patient care as their most important wellness-enhancing factor. PMID- 26989622 TI - A de novo transcriptome of the Malpighian tubules in non-blood-fed and blood-fed Asian tiger mosquitoes Aedes albopictus: insights into diuresis, detoxification, and blood meal processing. AB - Background. In adult female mosquitoes, the renal (Malpighian) tubules play an important role in the post-prandial diuresis, which removes excess ions and water from the hemolymph of mosquitoes following a blood meal. After the post-prandial diuresis, the roles that Malpighian tubules play in the processing of blood meals are not well described. Methods. We used a combination of next-generation sequencing (paired-end RNA sequencing) and physiological/biochemical assays in adult female Asian tiger mosquitoes (Aedes albopictus) to generate molecular and functional insights into the Malpighian tubules and how they may contribute to blood meal processing (3-24 h after blood ingestion). Results/Discussion. Using RNA sequencing, we sequenced and assembled the first de novo transcriptome of Malpighian tubules from non-blood-fed (NBF) and blood-fed (BF) mosquitoes. We identified a total of 8,232 non-redundant transcripts. The Malpighian tubules of NBF mosquitoes were characterized by the expression of transcripts associated with active transepithelial fluid secretion/diuresis (e.g., ion transporters, water channels, V-type H(+)-ATPase subunits), xenobiotic detoxification (e.g., cytochrome P450 monoxygenases, glutathione S-transferases, ATP-binding cassette transporters), and purine metabolism (e.g., xanthine dehydrogenase). We also detected the expression of transcripts encoding sodium calcium exchangers, G protein coupled-receptors, and septate junctional proteins not previously described in mosquito Malpighian tubules. Within 24 h after a blood meal, transcripts associated with active transepithelial fluid secretion/diuresis exhibited a general downregulation, whereas those associated with xenobiotic detoxification and purine catabolism exhibited a general upregulation, suggesting a reinvestment of the Malpighian tubules' molecular resources from diuresis to detoxification. Physiological and biochemical assays were conducted in mosquitoes and isolated Malpighian tubules, respectively, to confirm that the transcriptomic changes were associated with functional consequences. In particular, in vivo diuresis assays demonstrated that adult female mosquitoes have a reduced diuretic capacity within 24 h after a blood meal. Moreover, biochemical assays in isolated Malpighian tubules showed an increase in glutathione S-transferase activity and the accumulation of uric acid (an end product of purine catabolism) within 24 h after a blood meal. Our data provide new insights into the molecular physiology of Malpighian tubules in culicine mosquitoes and reveal potentially important molecular targets for the development of chemical and/or gene-silencing insecticides that would disrupt renal function in mosquitoes. PMID- 26989623 TI - From commensalism to parasitism in Carapidae (Ophidiiformes): heterochronic modes of development? AB - Phenotypic variations allow a lineage to move into new regions of the adaptive landscape. The purpose of this study is to analyse the life history of the pearlfishes (Carapinae) in a phylogenetic framework and particularly to highlight the evolution of parasite and commensal ways of life. Furthermore, we investigate the skull anatomy of parasites and commensals and discuss the developmental process that would explain the passage from one form to the other. The genus Carapus forms a paraphyletic grouping in contrast to the genus Encheliophis, which forms a monophyletic cluster. The combination of phylogenetic, morphologic and ontogenetic data clearly indicates that parasitic species derive from commensal species and do not constitute an iterative evolution from free-living forms. Although the head morphology of Carapus species differs completely from Encheliophis, C. homei is the sister group of the parasites. Interestingly, morphological characteristics allowing the establishment of the relation between Carapus homei and Encheliophis spp. concern the sound-producing mechanism, which can explain the diversification of the taxon but not the acquisition of the parasite morphotype. Carapus homei already has the sound-producing mechanism typically found in the parasite form but still has a commensal way of life and the corresponding head structure. Moreover, comparisons between the larval and adult Carapini highlight that the adult morphotype "Encheliophis" is obtained by going beyond the adult stage reached by Carapus. The entrance into the new adaptive landscape could have been realised by at least two processes: paedomorphosis and allometric repatterning. PMID- 26989624 TI - Updating movement estimates for American black ducks (Anas rubripes). AB - Understanding migratory connectivity for species of concern is of great importance if we are to implement management aimed at conserving them. New methods are improving our understanding of migration; however, banding (ringing) data is by far the most widely available and accessible movement data for researchers. Here, we use band recovery data for American black ducks (Anas rubripes) from 1951-2011 and analyze their movement among seven management regions using a hierarchical Bayesian framework. We showed that black ducks generally exhibit flyway fidelity, and that many black ducks, regardless of breeding region, stopover or overwinter on the Atlantic coast of the United States. We also show that a non-trivial portion of the continental black duck population either does not move at all or moves to the north during the fall migration (they typically move to the south). The results of this analysis will be used in a projection modeling context to evaluate how habitat or harvest management actions in one region would propagate throughout the continental population of black ducks. This analysis may provide a guide for future research and help inform management efforts for black ducks as well as other migratory species. PMID- 26989625 TI - Direct dating of Pleistocene stegodon from Timor Island, East Nusa Tenggara. AB - Stegodons are a commonly recovered extinct proboscidean (elephants and allies) from the Pleistocene record of Southeast Asian oceanic islands. Estimates on when stegodons arrived on individual islands and the timings of their extinctions are poorly constrained due to few reported direct geochronological analyses of their remains. Here we report on uranium-series dating of a stegodon tusk recovered from the Ainaro Gravels of Timor. The six dates obtained indicate the local presence of stegodons in Timor at or before 130 ka, significantly pre-dating the earliest evidence of humans on the island. On the basis of current data, we find no evidence for significant environmental changes or the presence of modern humans in the region during that time. Thus, we do not consider either of these factors to have contributed significantly to their extinction. In the absence of these, we propose that their extinction was possibly the result of long-term demographic and genetic declines associated with an isolated island population. PMID- 26989627 TI - The effect of ribosomal protein S15a in lung adenocarcinoma. AB - BACKGROUND: RPS15A (Ribosomal Protein S15A) promotes mRNA/ribosome interactions in translation. It is critical for the process of eukaryotic protein biosynthesis. Recently, aberrantly expressed RPS15A was found in the hepatitis virus and in malignant tumors. However, the role of RPS15A has not been fully revealed on the development of lung cancer. METHOD: In this study, a Tissue Microarray (TMA) of primary lung adenocarcinoma tissue specimens was carried out. Furthermore, to further investigate the function of RPS15A in lung cancer, RPS15A specific short hairpin RNA (shRNA) expressing lentivirus (Lv-shRPS15A) was constructed and used to infect H1299 and A549 cells. RESULT: Our data showed that RPS15A expression was increased in tumor tissues. Furthermore, the knockdown of RSP15A inhibited cancer cell growth and induced apoptosis in the cancer cells. Gene expression profile microarray also revealed that the P53 signaling pathway was activated in Lv-shRPS15A-infected cancer cells. CONCLUSION: Taken together, our results demonstrate that RPS15A is a novel oncogene in non-small cell lung cancer and may be a potential therapeutic target in lung cancer. PMID- 26989626 TI - Proteome-wide prediction of targets for aspirin: new insight into the molecular mechanism of aspirin. AB - Besides its anti-inflammatory, analgesic and anti-pyretic properties, aspirin is used for the prevention of cardiovascular disease and various types of cancer. The multiple activities of aspirin likely involve several molecular targets and pathways rather than a single target. Therefore, systematic identification of these targets of aspirin can help us understand the underlying mechanisms of the activities. In this study, we identified 23 putative targets of aspirin in the human proteome by using binding pocket similarity detecting tool combination with molecular docking, free energy calculation and pathway analysis. These targets have diverse folds and are derived from different protein family. However, they have similar aspirin-binding pockets. The binding free energy with aspirin for newly identified targets is comparable to that for the primary targets. Pathway analysis revealed that the targets were enriched in several pathways such as vascular endothelial growth factor (VEGF) signaling, Fc epsilon RI signaling and arachidonic acid metabolism, which are strongly involved in inflammation, cardiovascular disease and cancer. Therefore, the predicted target profile of aspirin suggests a new explanation for the disease prevention ability of aspirin. Our findings provide a new insight of aspirin and its efficacy of disease prevention in a systematic and global view. PMID- 26989628 TI - Genetic diversity and structure in the Endangered Allen Cays Rock Iguana, Cyclura cychlura inornata. AB - The Endangered Allen Cays Rock Iguana (Cyclura cychlura inornata) is endemic to the Allen Cays, a tiny cluster of islands in the Bahamas. Naturally occurring populations exist on only two cays (<4 ha each). However, populations of unknown origin were recently discovered on four additional cays. To investigate patterns of genetic variation among these populations, we analyzed nuclear and mitochondrial markers for 268 individuals. Analysis of three mitochondrial gene regions (2,328 bp) and data for eight nuclear microsatellite loci indicated low genetic diversity overall. Estimates of effective population sizes based on multilocus genotypes were also extremely low. Despite low diversity, significant population structuring and variation in genetic diversity measures were detected among cays. Genetic data confirm the source population for an experimentally translocated population while raising concerns regarding other, unauthorized, translocations. Reduced heterozygosity is consistent with a documented historical population decline due to overharvest. This study provides the first range-wide genetic analysis of this subspecies. We suggest strategies to maximize genetic diversity during ongoing recovery including additional translocations to establish assurance populations and additional protective measures for the two remaining natural populations. PMID- 26989629 TI - Occurrence patterns of coral-dwelling gall crabs (Cryptochiridae) over depth intervals in the Caribbean. AB - Coral-associated invertebrates form a major part of the diversity on reefs, but their distribution and occurrence patterns are virtually unstudied. For associated taxa data are lacking on their distribution across shelves and environmental gradients, but also over various depths. Off Curacao we studied the prevalence and density of coral-dwelling gall crabs (Cryptochiridae), obligate symbionts of stony corals. Belt transects (10 * 0.5m(2)) were laid out at 6, 12 and 18 m depth intervals at 27 localities. Twenty-one known host coral species were surveyed, measured, and the number of crab dwellings was recorded to study the influence of host occurrence, depth distribution, and colony size on the occurrence rates of three Atlantic gall crab species: Opecarcinus hypostegus, Troglocarcinus corallicola and Kroppcarcinus siderastreicola. The overall gall crab prevalence rate was 20.3% across all available host corals at all depths. The agariciid-associated species O. hypostegus was found to mostly inhabit Agaricia lamarcki and its prevalence was highest at deeper depths, following the depth distribution of its host. Kroppcarcinus siderastreicola, associated with Siderastrea and Stephanocoenia, inhabited shallower depths despite higher host availability at deeper depths. The generalist species T. corallicola showed no clear host or depth specialisation. These results show that the primary factors affecting the distribution and occurrence rates over depth intervals differed between each of the three Atlantic cryptochirid species, which in turn influences their vulnerability to reef degradation. PMID- 26989630 TI - Taxonomic revision of the Malagasy members of the Nesomyrmex angulatus species group using the automated morphological species delineation protocol NC-PART clustering. AB - Background. Applying quantitative morphological approaches in systematics research is a promising way to discover cryptic biological diversity. Information obtained through twenty-first century science poses new challenges to taxonomy by offering the possibility of increased objectivity in independent and automated hypothesis formation. In recent years a number of promising new algorithmic approaches have been developed to recognize morphological diversity among insects based on multivariate morphometric analyses. These algorithms objectively delimit components in the data by automatically assigning objects into clusters. Method. In this paper, hypotheses on the diversity of the Malagasy Nesomyrmex angulatus group are formulated via a highly automated protocol involving a fusion of two algorithms, (1) Nest Centroid clustering (NC clustering) and (2) Partitioning Algorithm based on Recursive Thresholding (PART). Both algorithms assign samples into clusters, making the class assignment results of different algorithms readily inferable. The results were tested by confirmatory cross-validated Linear Discriminant Analysis (LOOCV-LDA). Results. Here we reveal the diversity of a unique and largely unexplored fragment of the Malagasy ant fauna using NC-PART clustering on continuous morphological data, an approach that brings increased objectivity to taxonomy. We describe eight morphologically distinct species, including seven new species: Nesomyrmex angulatus (Mayr, 1862), N. bidentatus sp. n., N. clypeatus sp. n., N. devius sp. n., N. exiguus sp. n., N. fragilis sp. n., N. gracilis sp. n., and N. hirtellus sp. n.. An identification key for their worker castes using morphometric data is provided. Conclusions. Combining the dimensionality reduction feature of NC clustering with the assignment of samples into clusters by PART advances the automatization of morphometry-based alpha taxonomy. PMID- 26989631 TI - Scientific publications in nursing journals from Mainland China, Taiwan, and Hong Kong: a 10-year survey of the literature. AB - BACKGROUND: China has witnessed remarkable progress in scientific performance in recent years. However, the quantity and quality of nursing publications from three major regions (Mainland China, Taiwan, and Hong Kong) have not been reported. This study aimed to investigate the characteristics of scientific research productivity from Mainland China, Taiwan, and Hong Kong in the field of nursing. METHODS: Articles published in the 110 nursing journals originating from Mainland China, Taiwan, and Hong Kong between 2005 and 2014 were retrieved from the Web of Science. The total number of articles published, the impact factor, and the citation count were analyzed. RESULTS: There were 2,439 publications between 2005 and 2014 from China, including 438 from Mainland China, 1,506 from Taiwan, and 495 from Hong Kong. There was a significant increase in publications for these three regions (p < 0.05), especially for Mainland China, with a 59.50 fold increase experienced. From 2011, the number of publications from Mainland China exceeded that from Hong Kong. Taiwan had the highest total journal impact factor (2,142.81), followed by Hong Kong (720.39) and Mainland China (583.94). The mean journal impact factor from Hong Kong (1.46) was higher than that from Taiwan (1.42) and Mainland China (1.33). Taiwan had the highest total citation count (8,392), followed by Hong Kong (3,785) and Mainland China (1,493). The mean citation count from Hong Kong (7.65) was higher than that from Taiwan (5.57) and Mainland China (3.41). The Journal of Clinical Nursing was the most popular journal in the three regions. DISCUSSION: Chinese contributions to the field of nursing have significantly increased in the past ten years, particularly from Mainland China. Taiwan is the most productive region in China. Hong Kong had the highest-quality research output, according to mean journal impact factor and mean citation count. PMID- 26989632 TI - Serum uric acid levels during leprosy reaction episodes. AB - Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18-69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with type 2 leprosy reactions might be due to the consumption of UA to neutralize the enhanced production of oxygen- and nitrogen-reactive species that occurs during type 2 reactions. The maintenance of the reduced levels in the follow-up assessments may indicate persistence of oxidative stress in the initial post-treatment stages, despite improved clinical conditions. The results of this study suggest that serum UA may play an antioxidative role during type 2 leprosy reactions. PMID- 26989633 TI - Palatability and pharmacokinetics of flunixin when administered to sheep through feed. AB - Applying analgesics to feed is a potentially easy method of providing pain-relief to sheep and lambs that undergo painful husbandry procedures. To be effective, the medicated feed needs to be readily accepted by sheep and its consumption needs to result in therapeutic concentrations of the drug. In the present experiment, pelleted feed was supplemented with flunixin (4.0 mg/kg live weight) and offered to eight sheep. To test the palatability of flunixin, the individually penned sheep were offered normal feed and feed supplemented with flunixin in separate troughs for two consecutive days. A trend for a day by feed type (control versus flunixin supplemented) interaction suggested that sheep may have had an initial mild aversion to pellets supplemented with flunixin on the first day of exposure, however, by on the second day there was no difference in consumption of normal feed and feed supplemented with flunixin. To test pharmacokinetics, sheep were offered 800 g of flunixin supplemented feed for a 12 h period. Blood samples were taken over 48 h and plasma drug concentrations were determined using ultra-high-pressure liquid chromatography, negative electrospray ionisation and tandem mass spectrometry. The mean +/- S.D. time required to reach maximum concentration was 6.00 +/- 4.14 h and ranged from 1 to 12 h. Average maximum plasma concentration was 1.78 +/- 0.48 ug/mL and ranged from 1.61 to 2.80 ug/mL. The average half-life of flunixin was 7.95 +/- 0.77 h and there was a mean residence time of 13.62 +/- 1.17 h. Free access to flunixin supplemented feed enabled all sheep to obtain inferred therapeutic concentrations of flunixin in plasma within 6 h of starting to consume the feed. Provision of an analgesic in feed may be an alternative practical method for providing pain relief to sheep. PMID- 26989634 TI - Within-person variability in men's facial width-to-height ratio. AB - Background. In recent years, researchers have investigated the relationship between facial width-to-height ratio (FWHR) and a variety of threat and dominance behaviours. The majority of methods involved measuring FWHR from 2D photographs of faces. However, individuals can vary dramatically in their appearance across images, which poses an obvious problem for reliable FWHR measurement. Methods. I compared the effect sizes due to the differences between images taken with unconstrained camera parameters (Studies 1 and 2) or varied facial expressions (Study 3) to the effect size due to identity, i.e., the differences between people. In Study 1, images of Hollywood actors were collected from film screenshots, providing the least amount of experimental control. In Study 2, controlled photographs, which only varied in focal length and distance to camera, were analysed. In Study 3, images of different facial expressions, taken in controlled conditions, were measured. Results. Analyses revealed that simply varying the focal length and distance between the camera and face had a relatively small effect on FWHR, and therefore may prove less of a problem if uncontrolled in study designs. In contrast, when all camera parameters (including the camera itself) are allowed to vary, the effect size due to identity was greater than the effect of image selection, but the ranking of the identities was significantly altered by the particular image used. Finally, I found significant changes to FWHR when people posed with four of seven emotional expressions in comparison with neutral, and the effect size due to expression was larger than differences due to identity. Discussion. The results of these three studies demonstrate that even when head pose is limited to forward facing, changes to the camera parameters and a person's facial expression have sizable effects on FWHR measurement. Therefore, analysing images that fail to constrain some of these variables can lead to noisy and unreliable results, but also relationships caused by previously unconsidered confounds. PMID- 26989635 TI - ColoFinder: a prognostic 9-gene signature improves prognosis for 871 stage II and III colorectal cancer patients. AB - Colorectal cancer (CRC) is a heterogeneous disease with a high mortality rate and is still lacking an effective treatment. Our goal is to develop a robust prognosis model for predicting the prognosis in CRC patients. In this study, 871 stage II and III CRC samples were collected from six gene expression profilings. ColoFinder was developed using a 9-gene signature based Random Survival Forest (RSF) prognosis model. The 9-gene signature recurrence score was derived with a 5 fold cross validation to test the association with relapse-free survival, and the value of AUC was gained with 0.87 in GSE39582(95% CI [0.83-0.91]). The low-risk group had a significantly better relapse-free survival (HR, 14.8; 95% CI [8.17 26.8]; P < 0.001) than the high-risk group. We also found that the 9-gene signature recurrence score contributed more information about recurrence than standard clinical and pathological variables in univariate and multivariate Cox analyses when applied to GSE17536(p = 0.03 and p = 0.01 respectively). Furthermore, ColoFinder improved the predictive ability and better stratified the risk subgroups when applied to CRC gene expression datasets GSE14333, GSE17537, GSE12945and GSE24551. In summary, ColoFinder significantly improves the risk assessment in stage II and III CRC patients. The 9-gene prognostic classifier informs patient prognosis and treatment response. PMID- 26989636 TI - Molecular phylogeny of porcelain crabs (Porcellanidae: Petrolisthes and allies) from the south eastern Pacific: the genera Allopetrolisthes and Liopetrolisthes are not natural entities. AB - Porcelain crabs from the closely related genera Petrolisthes, Liopetrolisthes, and Allopetrolisthes are known for their diversity of lifestyles, habitats, and coloration. The evolutionary relationships among the species belonging to these three genera is not fully resolved. A molecular phylogeny of the group may help to resolve the long-standing taxonomic question about the validity of the genera Allopetrolisthes and Liopetrolisthes. Using both 'total evidence' and single marker analyses based on a 362-bp alignment of the 16S rRNA mitochondrial DNA and a 328-bp alignment of the Histone 3 nuclear DNA, the phylogenetic relationships among 11 species from Petrolisthes (6 species), Liopetrolisthes (2 species), and Allopetrolisthes (3 species), all native to the south eastern Pacific, were examined. The analyses supported three pairs of sister species: L. mitra + L. patagonicus, P. tuberculatus + P. tuberculosus, and A. angulosus + A. punctatus. No complete segregation of species, according to genera, was evident from tree topologies. Bayesian-factor analyses revealed strong support for the unconstrained tree instead of an alternative tree in which monophyly of the three genera was forced. Thus, the present molecular phylogeny does not support the separation of the species within this complex into the genera Petrolisthes, Liopetrolisthes, and Allopetrolisthes. Taking into account the above and other recent molecular phylogenetic analyses focused on other representatives from the family Porcellanidae, it is tentatively proposed to eliminate the genera Liopetrolisthes and Allopetrolisthes, and to transfer their members to the genus Petrolisthes. PMID- 26989637 TI - A new species of Psychrophrynella (Amphibia, Anura, Craugastoridae) from the humid montane forests of Cusco, eastern slopes of the Peruvian Andes. AB - We describe a new species of Psychrophrynella from the humid montane forest of the Department Cusco in Peru. Specimens were collected at 2,670-3,165 m elevation in the Area de Conservacion Privada Ukumari Llakta, Japumayo valley, near Comunidad Campesina de Japu, in the province of Paucartambo. The new species is readily distinguished from all other species of Psychrophrynella but P. bagrecito and P. usurpator by possessing a tubercle on the inner edge of the tarsus, and from these two species by its yellow ventral coloration on abdomen and limbs. Furthermore, the new species is like P. bagrecito and P. usurpator in having an advertisement call composed of multiple notes, whereas other species of Psychrophrynella whose calls are known have a pulsed call (P. teqta) or a short, tonal call composed of a single note. The new species has a snout-vent length of 16.1-24.1 mm in males and 23.3-27.7 mm in females. Like other recently described species in the genus, this new Psychrophrynella inhabits high-elevation forests in the tropical Andes and likely has a restricted geographic distribution. PMID- 26989638 TI - The role of sex and age in the architecture of intrapopulation howler monkey plant networks in continuous and fragmented rain forests. AB - We evaluated the structure of intrapopulation howler monkey-plant interactions by focusing on the plant species consumed by different sex and age classes in continuous and fragmented forests in southern Mexico. For this we used network analysis to evaluate the impact of fragmentation on howler population traits and on resource availability and food choice. A total of 37 tree and liana species and seven plant items (bark, immature fruits, flowers, mature fruits, immature leaves, mature leaves and petioles) were consumed, but their relative consumption varied according to sex and age classes and habitat type. Overall, adult females consumed the greatest number of plant species and items while infants and juveniles the lowest. For both continuous and fragmented forests, we found a nested diet for howler monkey-plant networks: diets of more selective monkeys represent subsets of the diets of other individuals. Nestedness was likely due to the high selectivity of early life stages in specific food plants and items, which contrasts with the generalized foraging behaviour of adults. Information on the extent to which different plant species and primate populations depend on such interactions in different habitats will help to make accurate predictions about the potential impact of disturbances on plant-animal interaction networks. PMID- 26989639 TI - Reducing bias in population and landscape genetic inferences: the effects of sampling related individuals and multiple life stages. AB - In population or landscape genetics studies, an unbiased sampling scheme is essential for generating accurate results, but logistics may lead to deviations from the sample design. Such deviations may come in the form of sampling multiple life stages. Presently, it is largely unknown what effect sampling different life stages can have on population or landscape genetic inference, or how mixing life stages can affect the parameters being measured. Additionally, the removal of siblings from a data set is considered best-practice, but direct comparisons of inferences made with and without siblings are limited. In this study, we sampled embryos, larvae, and adult Ambystoma maculatum from five ponds in Missouri, and analyzed them at 15 microsatellite loci. We calculated allelic richness, heterozygosity and effective population sizes for each life stage at each pond and tested for genetic differentiation (F ST and D C ) and isolation-by-distance (IBD) among ponds. We tested for differences in each of these measures between life stages, and in a pooled population of all life stages. All calculations were done with and without sibling pairs to assess the effect of sibling removal. We also assessed the effect of reducing the number of microsatellites used to make inference. No statistically significant differences were found among ponds or life stages for any of the population genetic measures, but patterns of IBD differed among life stages. There was significant IBD when using adult samples, but tests using embryos, larvae, or a combination of the three life stages were not significant. We found that increasing the ratio of larval or embryo samples in the analysis of genetic distance weakened the IBD relationship, and when using D C , the IBD was no longer significant when larvae and embryos exceeded 60% of the population sample. Further, power to detect an IBD relationship was reduced when fewer microsatellites were used in the analysis. PMID- 26989640 TI - Reproductive biology of the biofuel plant Jatropha curcas in its center of origin. AB - In this work, we studied the main characteristics of flowering, reproductive system and diversity of pollinators for the biofuel plant Jatropha curcas (L.) in a site of tropical southeastern Mexico, within its center of origin. The plants were monoecious with inflorescences of unisexual flowers. The male flowers produced from 3062-5016 pollen grains (266-647 per anther). The plants produced fruits with both geitonogamy and xenogamy, although insect pollination significantly increased the number and quality of fruits. A high diversity of flower visiting insects (36 species) was found, of which nine were classified as efficient pollinators. The native stingless bees Scaptotrigona mexicana (Guerin Meneville) and Trigona (Tetragonisca) angustula (Latreille) were the most frequent visitors and their presence coincided with the hours when the stigma was receptive. It is noteworthy that the female flowers open before the male flowers, favoring xenogamy, which may explain the high genetic variability reported in J. curcas for this region of the world. PMID- 26989641 TI - Evaluation of Chitosan-Tripolyphosphate Nanoparticles as a p-shRNA Delivery Vector: Formulation, Optimization and Cellular Uptake Study. AB - Polysaccharides (especially chitosan) have recently attracted much attention as gene therapy delivery vehicles for their unique properties such as biocompatibility, biodegradability, low toxicity, and controlled release. Nanoparticles have strong potential as a carrier of plasmid short hairpin RNA (p shRNA). This study aimed to find the optimum conditions for obtaining Chitosan/triphosphate (TPP)/p-shRNA nanoparticles by the ionic gelation method, and investigating the cellular uptake of the optimized nanoparticles. After applying the central composite design of response surface methodology (RSM), the optimum conditions for preparation of nanoparticles with small size and high loading efficiency were: chitosan/TPP ratio = 10, pH = 5.5 and N/P ratio = 11. The resulting nanoparticles had an average size of 172.8 +/- 7 nm and loading efficiency of 71.5 +/- 5%. SEM images showed spherical and smooth nanoparticles. The nanoparticles complexed with p-shRNA and may protect it against nuclease digestion. Cytotoxicity studies with HeLa and PC3 human cancer cells demonstrated that chitosan/TPP nanoparticles had low toxicity. Cellular uptake studies using HeLa cells showed that the nanoparticles entered the cells (cellular uptake) and delivered DNA, probably due to their favorable Zeta potential (approximately +28 mV) and small size. PMID- 26989642 TI - Rosai-Dorfman disease and the heart. AB - Rosai-Dorfman disease (RDD) is a non-malignant pathology of histiocyte proliferation. The classical clinical presentation is with painless cervical lymphadenopathy, but extranodal involvement is frequent, occurring in approximately 40% of cases. The literature was systematically reviewed to identify reported cases of RDD with cardiac involvement. Eighteen cases were identified (3 pediatric and 15 adult). In adult cardiac RDD (cRDD), three patterns of disease were noted: an intra-cardiac mass, epicardial involvement, and pulmonary artery involvement. Reported cases suggest that surgical excision of intra-cardiac masses confers a good prognosis. PMID- 26989643 TI - The progress of angiogenic factors in the development of leukemias. AB - Angiogenic factors have been demonstrated to play important roles in modulating angiogenesis of solid tumors. Recently, accumulating studies extensively indicated that some angiogenic factors widely exist in malignant cells of hematologic malignancy, which regulated the expression of a number of genes that were involved in abnormal proliferation, differentiation and apoptosis of these cells. With deep research of angiogenic factors, its expression, function and regulatory mechanism were gradually elucidated, and some of them were related to the development and prognosis of leukemia, or provide more possible strategies for treatment of patients with leukemia. Herein, we summarize the progress in study of some important angiogenic factors and hematological malignancies. PMID- 26989644 TI - Insulin-driven translational capacity is impaired in primary fibroblasts of Prader Willi. AB - Prader-Willi (PW) syndrome is a rare genetic disorder characterized by hypothalamic-pituitary abnormalities and severe hypotonia, hyperphagia, behavioural and psychiatric problems. Absence of satiety leads to severe obesity and frequently to diabetes. Furthermore, adult patients suffer from a severe loss of muscle mass, which severely impacts their quality of life. The mechanisms underlying alterations in muscle growth in PW remain to be clarified. In this study we explored the hypothesis that, in PW cells, alterations of protein synthesis are determined by dysfunctions in the promotion of cell growth. In order to study the molecular changes leading to dysfunction in protein translation, primary fibroblasts derived from four PW patients and five control subjects were used to study the insulin-mediated signaling pathway implicated in the control of protein synthesis by immunoblotting. Here we present, for the first time, evidences that the protein translation response to insulin is impaired in PW fibroblasts. Insulin alone has a major upregulatory effect on protein kinase B (AKT), glycogen synthase kinase (GSK3beta), while phosphorylation of p70S6K1 protein elongation factor controlled by mammalian target of rapamycin complex I (mTORC1) is reduced. In addition, we provide data that the response to insulin in PW cells can be restored by previous treatment with the amino acid L-Leucine (L-Leu). Our experiments in primary cell cultures demonstrate an impairment of insulin signaling that can be rescued by supplementation with the branched aminoacid L-Leu, indicating a possible therapeutic approach for alleviating muscle mass loss in PW patients. PMID- 26989645 TI - Importance of glucokinase -258G/A polymorphism in Asian Indians with post transplant and type 2 diabetes mellitus. AB - Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) are non-synonymous forms of diabetes. Glucokinase (GCK) plays a key role in glucose metabolism. The relationship between the GCK promoter and specific types of diabetes, such as PTDM and T2DM, in the Asian Indian population is unknown. We examined the occurrence of a specific GCK promoter variant (-258G/A) in patients with T2DM and PTDM. The case-control study enrolled 640 Asian Indian subjects, including controls (n = 250) and T2DM (n = 250), PTDM (n = 42), and non-post transplant diabetes mellitus (non-PTDM) (n = 98) patients. Purified Deoxyribonucleic acid (DNA) was genotyped with the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The digested PCR products were analyzed on 12% polyacrylamide gels. The anthropometric, biochemical, and clinical details of each group were documented. GCK -258G/A alleles and genotypes were not associated with T2DM. However, among PTDM subjects, we detected a higher frequency of heterozygotes (52.4%) and a positive association with alleles/genotypes. The results suggest that the promoter region (-258G/A) of GCK plays an important role in PTDM in Asian Indians. PMID- 26989646 TI - Using inpatient data to estimate the prevalence of Wegener's granulomatosis in China. AB - China lacks a registry for most rare diseases, so specific epidemiological data on those diseases are lacking. A strategy involving the DISMOD II model was recently formulated to estimate the epidemiological parameters of rare diseases, and this strategy has been used to study several rare diseases. The current study used this strategy to estimate the prevalence of one such rare disease, Wegener's granulomatosis (WG), in China based on its incidence, mortality, and rate of remission according to the software tool DISMOD II. The incidence of WG was calculated based on inpatient data from 100 hospitals throughout China. The cause specific mortality from WG was estimated based on data from the National Vital Statistics System of the United States and adjusted for the Chinese population. The rate of disease remission was based on the results of previous study. The current results indicated that the prevalence of WG in China is 1.94/100,000, which is slightly lower than that in Europe and the United States. The mean age at onset of WG in China was calculated to be 38.9 years for males and 39.3 years for females and the duration of disease was 28 years for both male and female patients. These figures are similar to published data from other countries. In conclusion, the DISMOD II model was used to estimate the prevalence of WG in China, providing a basis to evaluate the potential disease burden and orphan drug use by patients with WG. The DISMOD II model could be used to estimate the prevalence of other rare diseases. PMID- 26989647 TI - Castleman's disease of a submandibular mass diagnosed on Fine Needle Cytology: Report of a case with histopathological, immunocytochemical and imaging correlations. AB - Castleman's disease (CD) is an unusual inflammatory lymphoproliferative disorder of uncertain aetiology, mainly involving lymphatic tissue in the mediastinum, but also occurring in the neck, lung, abdomen, pelvis, skeletal muscle and retroperitoneum. Fine Needle Cytology (FNC) is a quick, cost-effective and safe diagnostic modality to investigate on organs involved by CD, also providing a guide to treatment and management of patients with lymphoadenopathy. We report a case of a 44-year-old man who underwent FNC of a submandibular mass with subsequent surgical excision. Cytology revealed an atypical lymphoproliferative process, which arose the suspicion of CD. Histopathological study of the excised masses combined with immunhistochemistry and imaging of the submandibular and neck areas, confirmed the suspicion. A final diagnosis of Unicentric Castleman's disease, hyaline-vascular type, was made. PMID- 26989648 TI - Peutz-Jeghers syndrome: Four cases in one family. AB - Peutz-Jeghers syndrome (PJS) is a rare, but life-threatening, familial inherited disease, characterized by mucocutaneous pigmentation and hamartomatous polyps. The estimated incidence of PJS ranges from 1/50,000 to 1/200,000. PJS can significantly increase the risk of malignancies, and especially gastrointestinal malignancies. Reported here are 4 cases of PJS in one family. PMID- 26989649 TI - A rare case of giant vaginal fibromyoma. AB - Vaginal fibroids rarely exist as a primary vaginal tumor. Approximately 300 cases have been reported in the literature. Here we are reporting a rare case of giant vaginal fibromyoma. It was diagnosed as cervical fibroid polyp preoperatively but found to be vaginal fibromyoma peroperatively. PMID- 26989650 TI - Spontaneous rectus sheath hematoma in a patient treated with apixaban. AB - Apixaban, a non-vitamin K antagonist oral anticoagulants, is a Factor Xa inhibitor that is prescribed for the treatment of non valvular atrial fibrillation. Rectus sheath hematoma is a rare but significant complication of oral anticoagulant treatment. The important causes of rectus sheath hematoma include treatment with anticoagulants, hematologic diseases, trauma, intense physical activity, coughing, sneezing and pregnancy. In this report, we describe case of a 71-year-old woman undergoing apixaban treatment for non valvular atrial fibrillation who presented with spontaneous rectus sheath hematoma. PMID- 26989651 TI - Coexistence of tinnitus and hyperacusis in individuals with auditory dys synchrony: A single case study. AB - Certain clinical pathologies affecting the ear and hearing mechanism may co exist. It is necessary to probe in detail into such conditions so that the pathophysiology is well understood. This research paper through a single case study tries to explain the probable pathophysiology behind coexistence of three different clinical conditions namely auditory dys-synchrony, hyperacusis and tinnitus. These conditions are common in the clinics, but the coexistence of all the three is rare and demands explanation beyond what is available in the literature. The assumed model highlights involvement of the outer hair cell's motor function in the cochlea along with the auditory central gain mechanism to explain possible pathophysiology behind coexistence of the three conditions. This model will provide insight into the probable link between the contribution of peripheral and central structures of hearing in generating tinnitus and hyperacusis in individuals having auditory dys-synchrony. PMID- 26989652 TI - Contact dermatitis after implantable cardiac defibrillator implantation for ventricular tachycardia. AB - Pacemaker contact sensitivity is a rare condition. Less than 30 reports of pacemaker skin reactions have been described. We report a 57-year-old woman who underwent an implantable cardiac defibrillator (ICD) implantation for ventricular tachycardia. A skin patch test was positive on almost all components of the pacemaker system. She was treated with topical corticosteroids and skin lesions resolved within 2 weeks. Because of widespread use of various devices, we will see this more often and therefore it is important to recognize this problem and its effective management. PMID- 26989653 TI - A large spontaneous intrahepatic portosystemic shunt in a cirrhotic patient. AB - A spontaneous portosystemic shunt is a rare malformation of the vessels supplying the liver. This condition often leads to the development of hepatic encephalopathy due to excessive shunting of blood from the portal vein to the inferior vena cava. Some studies have suggested that the presence of spontaneous portosystemic shunts is inversely associated with the appearance of large esophageal varices. Spontaneous intrahepatic portosystemic shunts (SIPSS) are far less frequently observed than extrahepatic portosystemic shunts, which include spleno-gastric-renal shunts, mesenteric-caval shunts, and a large patent umbilical vein. Reported here is a case of decompensated liver cirrhosis with a large SIPSS without any incidence of overt hepatic encephalopathy. PMID- 26989654 TI - Endovascular biopsy: Strategy for analyzing gene expression profiles of individual endothelial cells obtained from human vessels?. AB - PURPOSE: To develop a strategy of achieving targeted collection of endothelial cells (ECs) by endovascular methods and analyzing the gene expression profiles of collected single ECs. METHODS AND RESULTS: 134 ECs and 37 leukocytes were collected from four patients' intra-iliac artery endovascular guide wires by fluorescence activated cell sorting (FACS) and analyzed by single-cell quantitative RT-PCR for expression profile of 48 genes. Compared to CD45+ leukocytes, the ECs expressed higher levels (p < 0.05) of EC surface markers used on FACS and other EC related genes. The gene expression profile showed that these isolated ECs fell into two clusters, A and B, that differentially expressed 19 genes related to angiogenesis, inflammation and extracellular matrix remodeling, with cluster B ECs have demonstrating similarities to senescent or aging ECs. CONCLUSION: Combination of endovascular device sampling, FACS and single-cell quantitative RT-PCR is a feasible method for analyzing EC gene expression profile in vascular lesions. PMID- 26989655 TI - Defect Reperfusion Imaging with Sonazoid(r): A Breakthrough in Hepatocellular Carcinoma. PMID- 26989656 TI - The Effectiveness of Multiple Electrode Radiofrequency Ablation in Patients with Hepatocellular Carcinoma with Lesions More than 3 cm in Size and Barcelona Clinic Liver Cancer Stage A to B2. AB - Outcomes of hepatocellular carcinoma (HCC) lesions >3.0 cm in size including Barcelona Clinic Liver Cancer (BCLC) stage B after radiofrequency ablation (RFA) with a single electrode remain unsatisfactory. This study aimed to investigate the outcomes of RFA with multiple electrodes (ME-RFA) for HCC tumors 3.1-7.0 cm in size and BCLC stage B. This retrospective study included 70 consecutive patients with 58 medium- (3.1-5.0 cm) and 17 large- (5.1-7.0 cm) sized HCCs after ME-RFA using a controller. Outcomes in terms of complete response, primary technique effectiveness, local tumor progression, and overall survival were investigated. After 1-4 applications of ME-RFA, the rates of complete response and PTE in medium-sized tumors were 79.3% and 91.4%, respectively, and in large tumors were 76.5% and 94.1%, respectively. Overall, the major complication rate was 5.7%. After a median 21-month follow-up period, both two- and three-year estimated overall survival rates were above 80%. There were no significant differences in overall survival and local tumor progression rates between medium- and large-size tumors and among BCLC stages A, B1 and B2. A complete response to ME-RFA was the only significant factor associated with improved survival (p=0.008). In conclusion, ME-RFA can effectively treat 3.1-7.0-cm sized HCCs with a comparable outcome between medium- and large-size tumors and among BCLA stages A to B2. PMID- 26989657 TI - Clinical Characteristics of Patients with Cryptogenic Hepatocellular Carcinoma in a Hepatitis B Virus-Endemic Area. AB - OBJECTIVES: Chronic hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma (HCC) in South Korea, but a high prevalence of metabolic diseases may result in increases in the incidence of cryptogenic HCC (cHCC). We studied characteristics of the cHCC in a single-center cohort. METHODS: A cohort of 1,784 HCC patients newly diagnosed and treated at the National Cancer Center, Korea, between 2004 and 2009 was reviewed and analyzed. RESULTS: The cause of HCC was categorized as cHCC, HBV, hepatitis C virus (HCV), or alcohol. Overall, 162 (9.1%) patients of the HCC cohort had cHCC, and their mean age was 61.9 years. The median survival of cHCC patients was 24.7 months, which was the second shortest among the four groups after HBV HCC. cHCC patients had the largest tumor size (mean 7.4 cm) and the second highest proportion of poor prognostic factors such as the proportion of poorly defined tumors and extrahepatic spread in imaging studies. cHCC patients had better survival than HBV HCC patients according to multivariate analysis. Among cHCC patients, 137 (84.6%) had anti-HBc IgG antibodies, but this sub-group had different clinical features to those of HBV HCC patients. The body mass index (BMI) and hyperglycemia and hypercholesterolemia levels in cHCC patients were similar to those in HCV and alcoholic HCC patients. CONCLUSIONS: Anti-HBc IgG antibodies were present in most cHCC patients, but cHCC patients had better survival than HBV HCC patients on multivariate analysis. However, cHCC patients had a larger mean tumor size and more aggressive tumor characteristics than HCV HCC or alcoholic HCC patients did. It is hoped that this study will contribute to a better understanding of cHCC in HBV-endemic areas. PMID- 26989658 TI - Use of Transarterial Chemoembolization (TACE) and Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: US Regional Analysis of the GIDEON Registry. AB - BACKGROUND: Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Treatment with Sorafenib (GIDEON) is a worldwide, prospective, non-interventional study to evaluate the safety of sorafenib in a variety of patient subsets. METHODS: Eligible patients had unresectable hepatocellular carcinoma for whom the decision had been made to treat with sorafenib. Treatment strategies were instituted at the physician's discretion. Patient and disease characteristics, treatment practices, incidences of adverse events (AEs), and overall survival were collected. RESULTS: In the United States, 563 patients were evaluable for safety. Subgroup analysis was performed for patients who underwent transarterial chemoembolization (TACE) prior to the initiation of sorafenib (group A, n=158), after the initiation of sorafenib only (group B, n=29), both (group C, n=38), or did not undergo TACE (n=318). Patient demographics were similar across the groups. In group A, 29% had Child-Pugh score B or C at diagnosis, and 19% had Barcelona Clinic Liver Cancer tumor stage C or D. In group B, 48% had Child-Pugh score B or C at study entry, and 31% had BCLC stage C or D. The majority of patients in all groups initially received full-dose sorafenib. Incidences of grade >=3 drug-related AEs were 30%, 17%, and 16% in groups A, B, and C, respectively, and 22% in patients who did not undergo TACE. No new safety signals emerged. CONCLUSIONS: The results from GIDEON reaffirm that sorafenib can be safely used in the context of TACE. PMID- 26989659 TI - Breakthrough Imaging in Hepatocellular Carcinoma. PMID- 26989661 TI - Psycho-Biological Changes with Add on Yoga Nidra in Patients with Menstrual Disorders: a Randomized Clinical Trial. AB - INTRODUCTION: Menstrual disorders are common problems among women in the reproductive age group. Yuga interventions may decrease the physical and psychological problems related to menstrual disorders. The present study was aimed to assess the effect of Yoga Nidra on psychological problems in patients with menstrual disorders. METHODS: A total number of 100 women recruited from the department of obstetrics and gynecology and were then randomly allocated into two groups: a) intervention received yogic intervention and medication for 6 month, and b) control group received no yogic intervention and they only received prescribed medication). Psychological General Well-Being Index (PGWBI) and hormonal profile were assessed at the time of before and after six months on both groups. RESULTS: The mean score of anxiety, depression, positive well-being, general health, and vitality scores, as well as hormonal levels, in posttest were significantly different in intervention group as compared with pretest. But there was no significant difference in control group. CONCLUSION: Yoga Nidra can be a successful therapy to overcome the psychiatric morbidity associated with menstrual irregularities. Therefore, Yogic relaxation training (Yoga Nidra) could be prescribed as an adjunct to conventional drug therapy for menstrual dysfunction. PMID- 26989660 TI - Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI. AB - Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID- 26989662 TI - Emotional Support for New Graduated Nurses in Clinical Setting: a Qualitative Study. AB - INTRODUCTION: Newly graduated nurses experience many stressful situations during transition to practice. The provision of emotional support from more experienced nurses can ameliorate such work-related tension. Studies have not clearly specified the means through which such support could be most effectively provided; therefore the present study was conducted to explore the experiences of qualified nurses around the provision of emotional support to newly graduated nurses. METHODS: This qualitative study was conducted through semi-structured interviews with 18 qualified nurses. A purposive sampling approach was used for selection of participants. Interviews were transcribed verbatim and analyzed by the conventional content analysis method. The study took place from 2014-2015 in six teaching hospitals in the northwest of Iran. RESULTS: Emotional supports emerged in four following main-categories: Assurance, creating a sense of relaxation and security, lifting spirits, and emotional belonging and involvement. CONCLUSION: These results can help to establish an effective source of emotional support for newly graduated nurses. This can play an important role in reducing their stress and anxiety, in increasing their self-confidence and in forming a constructive relationship between them and qualified nurses. PMID- 26989663 TI - Strategies for Managing Nursing Students' Incivility as Experienced by Nursing Educators: a Qualitative Study. AB - INTRODUCTION: Students' incivility is an impolite and disturbing behavior in education and if ignored could lead to behavioral complexities and eventually violence and aggression in classrooms. This study aimed to reveal the experiences of Iranian educators regarding the management of such behaviors. METHODS: In this qualitative study, qualitative content analysis method was used to evaluate the experiences and perceptions of nursing educators and students. A total of 22 persons (14 educators and 8 students) were selected through purposive sampling and individually interviewed. RESULTS: Categories of unification of educators regarding behavioral management, teaching-learning strategy, friendship strategy and training through role playing, authority, appropriative decision-making and freedom, stronger relationships between students, reflection, and interactive educational environment were some strategies used by teachers for management of incivility. CONCLUSION: Educators suggested some strategies which could be used depending on uniqueness of behaviors and given situation. Educators and managers of medical fields can use these approaches in their classrooms to control uncivil behaviors. PMID- 26989664 TI - Nursing Students' Understanding of the Concept of Self-Esteem: a Qualitative Study. AB - INTRODUCTION: The concept of self-esteem has several definitions in different paradigms. Nursing has a unique and combined paradigm; therefore it is necessary to explore nursing students' understanding of the concept of self-esteem. The present study aimed to discover the extent and characteristics of the concept of self-esteem from the perspective of Iranian nursing students through a qualitative approach. METHODS: This study was conducted using the conventional content analysis method with the participation of 14 nursing students. Purposive sampling was used to recruit participants and data were collected through in depth semi-structured interviews and analyzed simultaneously. RESULTS: Study findings showed that the nursing students' self-esteem is related to the sense of worthy they perceived as being a nursing student. Nursing students' self-esteem was determined through sense of worthy related to their perceived professionalism level, socialization into the profession, and enthusing of them about being a nursing student. CONCLUSION: If a nursing student was proud of her or his nursing role, then he or she would enjoy the nursing course and all that entailed; such as communication with colleagues, performing the tasks and, generally her or his career. PMID- 26989665 TI - The Lived Experience of Iranian Women Confronting Breast Cancer Diagnosis. AB - INTRODUCTION: The populations who survive from breast cancer are growing; nevertheless, they mostly encounter with many cancer related problems in their life, especially after early diagnosis and have to deal with these problems. Except for the disease entity, several socio-cultural factors may affect confronting this challenge among patients and the way they deal with. Present study was carried out to prepare clear understanding of Iranian women's lived experiences confronting breast cancer diagnosis and coping ways they applied to deal with it. METHODS: This study was carried out by using qualitative phenomenological design. Data gathering was done through purposive sampling using semi-structured, in-depth interviews with 18 women who survived from breast cancer. The transcribed interviews were analyzed using Van Manen's thematic analysis approach. RESULTS: Two main themes were emerged from the interviews including "emotional turbulence" and "threat control". The first, comprised three sub themes including uncertainty, perceived worries, and living with fears. The second included risk control, recurrence control, immediate seeking help, seeking support and resource to spirituality. CONCLUSION: Emotional response was the immediate reflection to cancer diagnosis. However, during post-treatment period a variety of emotions were not uncommon findings, patients' perceptions have been changing along the time and problem-focused coping strategies have replaced. Although women may experience a degree of improvement and adjustment with illness, the emotional problems are not necessarily resolved, they may continue and gradually engender positive outcomes. PMID- 26989666 TI - Psychological Reactions among Patients with Chronic Hepatitis B: a Qualitative Study. AB - INTRODUCTION: Hepatitis B is the most prevalent type of viral hepatitis. Psychological reactions among patients with hepatitis B infection is considerably different and affects their decision about treating and following up the disease. The present study aims at explaining the psychological demonstrations experienced by these patients. METHODS: In this qualitative study, a total of 18 patients with hepatitis B (8 women and 10 men) were selected by purposive sampling method. Data were collected by unstructured in-depth interviews during 2014-2015 in the medical centers of three cities in Iran. All interviews were recorded, typed and analyzed by the conventional content analysis approach. RESULTS: By analyzing the data, the main theme including psychological instability, with three sub-themes were emerged: grief reaction (stupor, denial, anger and aggression), emotional challenges (worry and apprehension, contradiction with beliefs, fear of deprivation, fear of stigma, waiting for death and prognosis ambiguity) and inferiority complex (social withdrawal, sense of humiliation and embarrassment and sense of guilt and blame) were acquired. CONCLUSION: The findings indicate that patients with hepatitis B experience various psychological reactions that need to be controlled and managed by themselves or healthcare providers. Thus, implementation of health interventions with emphasis on psychological care to prevent problems and execution of educational and consultation programs about hepatitis especially by medical centers and mass media is seems necessary. PMID- 26989667 TI - Effect of Combined Use of Calcium and Vitamin B6 on Premenstrual Syndrome Symptoms: a Randomized Clinical Trial. AB - INTRODUCTION: Premenstrual syndrome is one of the most common disorders in women, which includes a group of psychological and physical symptoms. The aim of this study was to examine the impact of combined use of calcium and vitamin B6 on premenstrual syndrome symptoms. METHODS: This double blind randomized controlled was carried out on 76 students of Hamadan University of Medical Sciences. Students were randomly allocated to two groups. (38 people in each group). Student in intervention groups received calcium tablet (500mg) and vitamin B6 (40 mg) and student in intervention groups received only vitamin B6 twice a day for two consecutive months. The symptoms were assessed by Beck depression inventory (BDI) and daily symptom records (DSR) questionnaires. Analyses were carried out by test-retest method, Chi-square, Mann-Whitney, Independent t-test, and paired t test using SPSS software ver.13. Results The result showed that although the severity of symptoms decreased in both groups, but this reduction was more significant in the combined calcium and vitamin B6 group. CONCLUSION: According to the result, using of combination of calcium and vitamin B6 leads to better controlling of the premenstrual syndrome symptoms. Therefore it is recommended for women who suffer from these syndromes. PMID- 26989668 TI - The Prevalence of Job Stress and its Relationship with Burnout Syndrome among the Academic Members of Lorestan University of Medical Sciences. AB - INTRODUCTION: Burnout syndrome is one of the consequences and the results of occupational or job stress emerged in the form of emotional exhaustion feeling, depersonalization and decrement personal accomplishment. The aim of this study was to determine the occupational stress and its relationship with burnout syndrome in the academic members of Lorestan University of Medical Sciences. METHODS: This descriptive cross-sectional survey was conducted on 111 of the faculty members via multistage sampling. Data were collected by the questionnaire of Maslach Burnout Inventory (MBI), and Osipow Occupational Stress Inventory (OSI R). Data were analyzed by using descriptive statistics as well as analytical statistics such as chi square, Kruskal-Wallis, Mann Whitney tests and Pearson correlation coefficient. RESULTS: The results showed that the most of the participants had a low level of burnout three dimensions including emotional burnout (72.1%), depersonalization (81.1%), and the decrement of personal accomplishment (56.8%). Moreover 79.3% of samples had a low occupational stress, but there was a meaningful relationship between occupational stress and dimensions of burnout syndrome with an exception for the intensity of decrement of personal accomplishment. CONCLUSION: Academic members were in an appropriate condition concerning burnout syndrome and occupational stress. However by applying some strategies to decrease stress and determining stress resources, we can improve their psychological health of academic members. PMID- 26989669 TI - The Effect of Recorded Mum's Lullaby and Brahm's Lullaby on Oxygen Saturation in Preterm Infants: a Randomized Double-Blind Clinical Trial. AB - INTRODUCTION: Music stimulation has been shown to provide significant benefits to preterm infants. Thus the aim of this study was determine the effect of recorded mum's lullaby and Brahm's lullaby on oxygen saturation in preterm infants. METHODS: This double-blind randomized controlled trial was carried out on 66 premature newborns with the postnatal age of >=3 days and weight <= 2800 grams at Taleghani Hospital. Infants were randomly divided into three groups: control, Brahm's lullaby and Mum's lullaby groups. Infants were continuously monitored for primary outcome of percutaneous oxygen saturation, for three consecutive sessions. RESULTS: There were significant difference in neonate oxygen saturation between the Brahm's lullaby and Mum's lullaby as compared with control groups in the 15 minutes after intervention. CONCLUSION: This study showed beneficial effects of Brahm's lullaby and Mum's lullaby sound. Therefore; it may be used for improving short term outcomes in premature infants. PMID- 26989670 TI - Health care associated infections, antibiotic resistance and clinical outcome: A surveillance study from Sanandaj, Iran. AB - AIM: To study the antibiotic susceptibility patterns of gram-negative healthcare associated bacterial infections at two tertiary hospitals in the Sanandaj city, Kurdistan Province, Iran. METHODS: From January 2012 to December 2012, all positive cultures from potentially sterile body fluids were gathered. They sent to professor Alborzi clinical microbiology center in Shiraz for further analysis and susceptibility testing. The antibiotic susceptibility was determined using the Kirby-Bauer method (disk diffusion technique). The Results were interpreted according to Clinical and Laboratory Standards Institute guidelines against a series of antimicrobials. World Health Organization definitions for Healthcare associated infections were followed. RESULTS: Seven hundred and thirty-two positive cultures were reported from both hospitals. Seventy-nine isolates/patients fulfilled the study criteria for health-care associated gram negative infections. The most frequent bacterial cultures were from the pediatric wards (52%). Serratia marcescens (S. marcescens) (38%) Escherichia coli (E. coli) (19%), Klebsiella pneumoniae (K. pneumoniae) (19%), Acinetobacter baumannii (6%), Enterobacter species (6%), Serratia odorifera (4%) and Pseudomonas species (5%) were the most frequently isolated organisms. The susceptibility pattern of common isolates i.e., S. marcescens, E. coli and K. pneumoniae for commonly used antibiotics were as follows: Ampicillin 3.3%, 6.7%, 20%; gentamicin 73.3%, 73.3%, 46.7%; ceftazidim 80%, 73.3%, 33.3%; cefepim 80%, 86.7%, 46.7%; piperacillin/tazobactam 90%, 66.7%, 86.7%; ciprofloxacin 100%, 73.3%, 86.7%; imipenem 100%, 100%, 100%, respectively. CONCLUSION: The most effective antibiotics against gram-negative healthcare associated infections are imipenem followed by ciprofloxacin. The resistance rate is high against ampicillin and cephalothin. The high mortality rate (46.1%) associated with S. marcescens is alarming. PMID- 26989671 TI - Hepatitis B surface antigen escape mutations: Indications for initiation of antiviral therapy revisited. AB - Approximately 240 million people are chronically infected with hepatitis B. The implementation of rigorous vaccination programs has led to an overall decrease in the prevalence of this disease worldwide but this may also have led to emergence of viral mutations that can escape the protection of hepatitis B surface antibody. As this phenomenon is increasingly recognized, concern for transmission to vaccinated individuals has also been raised. Herein, we describe two cases where the suspected presence of a hepatitis B surface antigen escape mutation impacted the decision to initiate early antiviral therapy, as well as provide a brief review of these mutations. Our findings described here suggest that a lower threshold for initiating therapy in these individuals should be considered in order to reduce the risk of transmission, as vaccination does not provide protection. PMID- 26989672 TI - Fulminant isolated cardiac sarcoidosis with pericardial effusion and acute heart failure: Challenging aspects of diagnosis and treatment. AB - This case report illustrates challenging aspects of diagnosis and treatment of isolated sarcoid heart disease (SHD) and the role of cardiovascular magnetic resonance (CMR) imaging. Here, we present a previously healthy 45-year-old man, who was admitted with pericardial effusion and symptoms of acute heart failure. CMR followed by targeted left ventricular endomyocardial biopsy (EMB) revealed the diagnosis of isolated SHD. The combined use of CMR and EMB was crucial in diagnosing SHD. Furthermore, this case report demonstrates the value of CMR for monitoring response to therapy and lesion healing. PMID- 26989673 TI - Hepatitis C virus positive patient diagnosed after detection of atypical cryoglobulin. AB - A 60-year-old male patient presented with jaundice and dark urine for three days, icteric sclerae and skin rash on his legs for six months. Laboratory investigations revealed an atypical cryoglobulinemia with high hepatitis C virus (HCV)-RNA levels. Imaging studies showed cholestasis was accompanying HCV. Capillary zone electrophoresis using immunosubtraction method revealed a polyclonal immunoglobulin G and immunoglobulin A (IgA) monoclonal cryoglobulin and that IgA lambda was absent in immunofixation electrophoresis. After a liver biopsy, chronic hepatitis C, HCV related mixed cryoglobulinemia and cryoglobulinemic vasculitis were diagnosed and antiviral therapy was initiated. Our HCV patient presented with cryoglobulinemic symptoms with an atypical cryoglobulinemia that was detected by an alternative method: Immunosubtraction by capillary electrophoresis. Different types of cryoglobulins may therefore have a correlation with clinical symptoms and prognosis. Therefore, the accurate immunotyping of cryoglobulins with alternative methods may provide more information about cryoglobulin-generated pathology. PMID- 26989674 TI - Combination therapy with daclatasvir and asunaprevir for dialysis patients infected with hepatitis C virus. AB - The standard antiviral therapy for dialysis patients infected with hepatitis C virus (HCV) is (pegylated) interferon monotherapy, but its efficacy is insufficient. Oral direct-acting antiviral agents (DAAs) have recently been developed for chronic hepatitis C patients. However, some DAAs have contraindications for chronic renal failure (CRF). Daclatasvir and asunaprevir are metabolized largely in the liver and are not contraindicated in CRF. Combination therapy with daclatasvir and asunaprevir was used for 4 dialysis patients infected with genotype 1b HCV. One patient had viral breakthrough, and the 3 others had sustained virological response 12. One patient was admitted for heart failure and percutaneous coronary intervention due to concomitant ischemic disease. Heart failure was unlikely to be caused by the combination therapy, as it was probably due to water overload. The patient continued to receive the combination therapy after the remission of the heart failure. The combination therapy was well tolerated in the other patients. PMID- 26989675 TI - Hypertension in the liver clinic - polyarteritis nodosa in a patient with hepatitis B. AB - Chronic hepatitis caused by hepatitis B virus (HBV) is an endemic disease in India. It is associated with extrahepatic manifestations like polyarteritis nodosa (PAN) which is a vasculitis like disorder, presenting in subacute or chronic phase; involving visceral and systemic vessels. It should always be considered as a possible etiology of hypertension in an underlying setting of hepatitis B. We describe a 56-year-male patient with a history of chronic HBV who presented to the outpatient clinic with history of recent onset hypertension and suspected liver disease. Further work up for the cause of recent hypertension included a contrast computerized tomography of abdomen, which revealed concomitant pathologies of chronic liver disease and multiple aneurysms in bilateral kidneys. This case illustrates the unusual presentation of extrahepatic manifestation of viral hepatitis in the form of PAN of kidneys. PAN as an independent entity may be missed in specialized clinics evaluating liver pathologies, due to its insidious onset, atypical clinical symptoms and multi systemic manifestations. The knowledge of extrahepatic, renal and vascular manifestations of hepatitis B unrelated to liver disease should be considered by physicians at the time of diagnosis and management of patients with HBV. PMID- 26989677 TI - Novel Biomarkers and Treatments of Cardiac Diseases. PMID- 26989676 TI - Associations of Polymorphisms in HRH2, HRH3, DAO, and HNMT Genes with Risk of Chronic Heart Failure. AB - The pathophysiological functions of cardiac histamine level and related histamine receptors during the development of chronic heart failure (CHF) were intensively investigated previously. However, the relevance of polymorphisms in histamine related genes, such as HRH2, HRH3, DAO, and HNMT, with CHF remains largely neglected. This study herein aims to analyze the clinical associations of polymorphisms in those genes with CHF risk. A total of 333 unrelated Chinese Han CHF patients and 354 ethnicity-matched healthy controls were recruited and 11 single nucleotide polymorphisms (SNPs) were genotyped. We found that the HRH3 rs3787429 polymorphism was associated with CHF risk (p < 0.001). The T allele of rs3787429 exhibited protective effect against CHF under the dominant (ORs = 0.455; 95% CIs = 0.322-0.642) and additive models (ORs = 0.662; 95% CIs = 0.523 0.838), while, for SNPs in HRH2, DAO, and HNMT, no significant associations were observed in the present study. These findings for the first time screen out one SNP (rs3787429) of HRH3 gene that was significantly associated with CHF in Chinese Han population, which may be a novel biomarker for personal prevention and treatment of CHF and provides novel highlights for investigating the contribution of this disease. PMID- 26989678 TI - The Association between Abnormal Long Noncoding RNA MALAT-1 Expression and Cancer Lymph Node Metastasis: A Meta-Analysis. AB - Previous studies have investigated that the expression levels of MALAT-1 were higher in cancerous tissues than matched histologically normal tissues. And, to some extent, overexpression of MALAT-1 was inclined to lymph node metastasis. This meta-analysis collected all relevant articles and explored the association between MALAT-1 expression levels and lymph node metastasis. We searched PubMed, EmBase, Web of Science, Cochrane Library, and OVID to address the level of MALAT 1 expression in cancer cases and noncancerous controls (accessed February 2015). And 8 studies comprising 696 multiple cancer patients were included to assess this association. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were calculated to assess the strength of the association using Stata 12.0 version software. The results revealed there was a significant difference in the incidence of lymph node metastasis between high MALAT-1 expression group and low MALAT-1 expression group (OR = 1.94, 95% CI 1.15-3.28, P = 0.013 random-effects model). Subgroup analysis indicated that MALAT-1 high expression had an unfavorable impact on lymph node metastasis in Chinese patients (OR = 1.87, 95% CI 1.01-2.46). This study demonstrated that the incidence of lymph node metastasis in patients detected with high MALAT-1 expression was higher than that in patients with low MALAT-1 expression in China. PMID- 26989679 TI - Immunologic Changes Implicated in the Pathogenesis of Focal Segmental Glomerulosclerosis. AB - Focal segmental glomerulosclerosis is a histological pattern on renal biopsy caused by diverse mechanisms. In its primary form, a circulatory factor is implicated in disease onset and recurrence. The natural history of primary FSGS is unpredictable, since some patients are unresponsive towards immunosuppressive measures. Immunologic changes, leading to a proinflammatory or profibrotic milieu, have been implicated in disease progression, namely, glomerular scarring, eventually leading to end-stage renal disease. Among these, interleukin-1beta, tumor-necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1) have emerged as important factors. Translating these findings into clinical practice dampened the enthusiasm, since both TNF-alpha and TGF-beta1 blockade failed to achieve significant control of the disease. More recently, a role of the complement system has been demonstrated which in fact may be another attractive target in clinical practice. Rituximab, blocking CD20-bearing cells, demonstrated conflicting data regarding efficacy in FSGS. Finally, the T-cell costimulating molecule B7-1 (CD80) is implicated in development of proteinuria in general. Blockade of this target demonstrated significant benefits in a small cohort of resistant patients. Taken together, this review focuses on immunology of FSGS, attributable to either the disease or progression, and discusses novel therapeutic approaches aiming at targeting immunologic factors. PMID- 26989680 TI - New Prognostic and Predictive Markers in Head and Neck Tumors. PMID- 26989681 TI - Cohort Records Study of 19,655 Women Who Received Postabortion Care in a Tertiary Hospital 2010-2013 in China: What Trends Can Be Observed? AB - The retrospective cohort epidemiological study was to investigate the characteristics of women who underwent induced abortion. Data were retrospectively collected from women who underwent induced abortions (n = 19,655) at the Xiamen Maternity and Child Health Care Hospital (2010-2013). The characteristics of women who underwent induced abortions included mean age, unmarried status, no previous deliveries, first pregnancy, >=2 abortions including the current one, and a history of caesarian section. From 2010 to 2013, mean age increased and declines were observed in the ratio of induced abortions to live births, the proportion of induced abortions among women of 15-24 years, those who were unmarried, had their first pregnancy, or had no history of delivery. However, the rates of induced abortions increased among women who were lactating, had a history of caesarian section, or had an interpregnancy interval of <6 months. This snapshot of induced abortions in China might suggest that the numbers are increasing but the ratio to live births has fallen. Methods should be improved to prevent unwanted pregnancies and reduce the number of induced abortions in China. It must be emphasized that differences in mentality and culture between countries might limit the representativeness of these results. PMID- 26989683 TI - Short-Term Side Effects after Radioiodine Treatment in Patients with Differentiated Thyroid Cancer. AB - OBJECTIVES: I-131 therapy for differentiated thyroid cancer (DTC) could induce adverse effects. The purpose of this study was to report and analyze symptoms after I-131 treatment within the hospitalization and present relevant medical intervention. METHODS: I-131 doses ranging from 3.7 to 9.25 GBq (100-250 mCi) were administrated for thyroid remnant ablation or treating DTC metastases. 117 patients with DTC for I-131 therapy were monitored through the video and intercommunicating with standardized questionnaire at different time points after I-131 oral administration. Adverse effects were recorded and relevant clinical factors were analyzed. RESULTS: Among all the 117 patients, 55 cases complained of neck's pain or swelling and 79 cases presented with gastrointestinal symptoms. Pain or swelling of salivary gland occurred in 15 patients, headache and vertigo in 10, insomnia in 9, vocal cord paralysis in 6, fatigue or general malaise in 6, and foreign body sensation in 5. Body numbness and urinary symptoms were observed in only 1 case, respectively. Those side effects were related with sex, pre-I-131 treatment TSH levels, frequency of I-131 therapy, and lymph node metastases. CONCLUSIONS: Short-term side effects after I-131 therapy for DTC patients varied individually; severe symptoms were not uncommon but generally did not need emergent medical intervention. PMID- 26989682 TI - Activation of the Extracellular Signal-Regulated Kinase Signaling Is Critical for Human Umbilical Cord Mesenchymal Stem Cell Osteogenic Differentiation. AB - Human umbilical cord mesenchymal stem cells (hUCMSCs) are recognized as candidate progenitor cells for bone regeneration. However, the mechanism of hUCMSC osteogenesis remains unclear. In this study, we revealed that mitogen-activated protein kinases (MAPKs) signaling is involved in hUCMSC osteogenic differentiation in vitro. Particularly, the activation of c-Jun N-terminal kinases (JNK) and p38 signaling pathways maintained a consistent level in hUCMSCs through the entire 21-day osteogenic differentiation period. At the same time, the activation of extracellular signal-regulated kinases (ERK) signaling significantly increased from day 5, peaked at day 9, and declined thereafter. Moreover, gene profiling of osteogenic markers, alkaline phosphatase (ALP) activity measurement, and alizarin red staining demonstrated that the application of U0126, a specific inhibitor for ERK activation, completely prohibited hUCMSC osteogenic differentiation. However, when U0126 was removed from the culture at day 9, ERK activation and osteogenic differentiation of hUCMSCs were partially recovered. Together, these findings demonstrate that the activation of ERK signaling is essential for hUCMSC osteogenic differentiation, which points out the significance of ERK signaling pathway to regulate the osteogenic differentiation of hUCMSCs as an alternative cell source for bone tissue engineering. PMID- 26989685 TI - Biological Insights into Myeloma and Other B Cell Malignancies. PMID- 26989684 TI - Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis. AB - Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett's esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice. PMID- 26989686 TI - The Impact of Personality Traits on the Outcome of Total Knee Arthroplasty. AB - Ten to twenty percent of patients with total knee arthroplasty (TKA) are dissatisfied with their clinical outcome. Aim of this study was to investigate the impact of personality traits on the subjective outcome of TKA. We investigated 80 patients with 86 computer navigated TKAs. We asked for patients satisfaction and divided patients into two groups (satisfied or dissatisfied). 12 personality traits were tested by the Freiburg Personality Inventory (FPI-R). Postoperative examination included Knee Society Score (KSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the Visual Analogue Scale (VAS). Radiologic investigation was done in all patients. 84% of our patients were satisfied, while 16% were not satisfied. The FPI-R showed statistical significant influence of four personality traits on patient satisfaction: life satisfaction (p = 0.006), performance orientation (p = 0.015), somatic distress (p = 0.001), and emotional stability (p = 0.002). All clinical scores (VAS, WOMAC, and KSS) showed significantly better results in the satisfied patient. Radiological examination showed optimal alignment of all TKAs. There were no complications requiring revision surgery. The results of our study show that personality traits may influence patients satisfaction and clinical outcome after TKA. Therefore patients personality traits may be a useful predictive factor for postoperative satisfaction after TKA. PMID- 26989687 TI - G-CSF Administration after the Intraosseous Infusion of Hypertonic Hydroxyethyl Starches Accelerating Wound Healing Combined with Hemorrhagic Shock. AB - OBJECTIVE: To evaluate the therapeutic effects of G-CSF administration after intraosseous (IO) resuscitation in hemorrhagic shock (HS) combined with cutaneous injury rats. METHODS: The rats were randomly divided into four groups: (1) HS with resuscitation (blank), (2) HS with resuscitation + G-CSF (G-CSF, 200 MUg/kg body weight, subcutaneous injection), (3) HS with resuscitation + normal saline solution injection (normal saline), and (4) HS + G-CSF injection without resuscitation (Unres/G-CSF). To estimate the treatment effects, the vital signs of alteration were first evaluated, and then wound closure rates and homing of MSCs and EPCs to the wound skins and vasculogenesis were measured. Besides, inflammation and vasculogenesis related mRNA expressions were also examined. RESULTS: IO infusion hypertonic hydroxyethyl starch (HHES) exhibited beneficial volume expansion roles and G-CSF administration accelerated wound healing 3 days ahead of other groups under hemorrhagic shock. Circulating and the homing of MSCs and EPCs at wound skins were significantly elevated at 6 h after G-CSF treatment. Inflammation was declined since 3 d while angiogenesis was more obvious in G-CSF treated group on day 9. CONCLUSIONS: These results suggested that the synergistical application of HHES and G-CSF has life-saving effects and is beneficial for improving wound healing in HS combined with cutaneous injury rats. PMID- 26989689 TI - The Role of (99m)Tc-Annexin V Apoptosis Scintigraphy in Visualizing Early Stage Glucocorticoid-Induced Femoral Head Osteonecrosis in the Rabbit. AB - OBJECTIVE: To validate the ability of (99m)Tc-Annexin V to visualize early stage of glucocorticoid-induced femoral head necrosis by comparing with (99m)Tc-MDP bone scanning. METHODS: Femoral head necrosis was induced in adult New Zealand white rabbits by intramuscular injection of methylprednisolone. (99m)Tc-Annexin scintigraphy and (99m)Tc-MDP scans were performed before and 5, 6, and 8 weeks after methylprednisolone administration. Rabbits were sacrificed at various time points and conducted for TUNEL and H&E staining. RESULTS: All methylprednisolone treated animals developed femoral head necrosis; at 8 weeks postinjection, destruction of bone structure was evident in H&E staining, and apoptosis was confirmed by the TUNEL assay. This was matched by (99m)Tc-Annexin V images, which showed a significant increase in signal over baseline. Serial (99m)Tc-Annexin V scans revealed that increased (99m)Tc-Annexin V uptake could be observed in 5 weeks. In contrast, there was no effect on (99m)Tc-MDP signal until 8 weeks. The TUNEL assay revealed that bone cell apoptosis occurred at 5 weeks. CONCLUSION: (99m)Tc-Annexin V is superior to (99m)Tc-MDP for the early detection of glucocorticoid-induced femoral head necrosis in the rabbit and may be a better strategy for the early detection of glucocorticoid-induced femoral head necrosis in patients. PMID- 26989688 TI - Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction. AB - Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model. PMID- 26989690 TI - Treating Small Bowel Obstruction with a Manual Physical Therapy: A Prospective Efficacy Study. AB - Small bowel obstructions (SBOs) caused by adhesions are a common, often life threatening postsurgical complication with few treatment options available for patients. This study examines the efficacy of a manual physical therapy treatment regimen on the pain and quality of life of subjects with a history of bowel obstructions due to adhesions in a prospective, controlled survey based study. Changes in six domains of quality of life were measured via ratings reported before and after treatment using the validated Small Bowel Obstruction Questionnaire (SBO-Q). Improvements in the domains for pain (p = 0.0087), overall quality of life (p = 0.0016), and pain severity (p = 0.0006) were significant when average scores before treatment were compared with scores after treatment. The gastrointestinal symptoms (p = 0.0258) domain was marginally significant. There was no statistically significant improvement identified in the diet or medication domains in the SBO-Q for this population. Significant improvements in range of motion in the trunk (p <= 0.001), often limited by adhesions, were also observed for all measures. This study demonstrates in a small number of subjects that this manual physical therapy protocol is an effective treatment option for patients with adhesive small bowel obstructions as measured by subject reported symptoms and quality of life. PMID- 26989691 TI - VOCs-Mediated Location of Olive Fly Larvae by the Braconid Parasitoid Psyttalia concolor: A Multivariate Comparison among VOC Bouquets from Three Olive Cultivars. AB - Herbivorous activity induces plant indirect defenses, as the emission of herbivorous-induced plant volatiles (HIPVs), which could be used by parasitoids for host location. Psyttalia concolor is a larval pupal endoparasitoid, attacking a number of tephritid flies including B. oleae. In this research, we investigated the olfactory cues routing host location behavior of P. concolor towards B. oleae larvae infesting three different olive cultivars. VOCs from infested and healthy fruits were identified using GC-MS analyses. In two-choice behavioral assays, P. concolor females preferred infested olive cues, which also evoked ovipositional probing by female wasps. GC-MS analysis showed qualitative and quantitative differences among volatiles emitted by infested and healthy olives. Volatile emissions were peculiar for each cultivar analyzed. Two putative HIPVs were detected in infested fruits, regardless of the cultivar, the monoterpene (E)-beta ocimene, and the sesquiterpene (E-E)-alpha-farnesene. Our study adds basic knowledge to the behavioral ecology of P. concolor. From an applied point of view, the field application of the above-mentioned VOCs may help to enhance effectiveness of biological control programs and parasitoid mass-rearing techniques. PMID- 26989692 TI - Dissemination of Extended-Spectrum beta-Lactamase- and AmpC beta-Lactamase Producing Escherichia coli within the Food Distribution System of Ho Chi Minh City, Vietnam. AB - To investigate the dissemination of ESBL/pAmpC-producing E. coli within the food distribution system of Ho Chi Minh City (HCMC), Vietnam, the prevalence of ESBL/pAmpC-producing E. coli strains in chicken meat, pork, beef, and fish/shrimp samples obtained from slaughterhouses, a wholesale market, and supermarkets was examined. Among the total of 330 collected food samples, ESBL/pAmpC-producing E. coli was detected in 150 samples (45.5%). The highest prevalence of these isolates was in chicken meat (76/82, 92.7%), followed by pork (32/92, 34.8%), beef (18/74, 34.3%), and fish/shrimp (24/82, 29.3%). A total of 342 strains of ESBL/pAmpC-producing E. coli were isolated from 150 positive food samples. The most prevalent genes responsible for ESBL or pAmpC activity belonged to the CTX-M 9 (110/342, 31.2%), CTX-M-1 (102/342, 29.8%), and CIT (118/342, 34.5%) groups. To our knowledge, this is the first report of the high occurrence of pAmpC (37.1%) in animal-based food in Vietnam. Among the 342 total ESBL/pAmpC-producing E. coli isolates, 276 (80.7%) were resistant to at least 6 antibiotic agents. Notably, high percentages of resistance to ciprofloxacin and fosfomycin were found in isolates from chicken (80.5% and 50.8%, resp.). These findings demonstrate that animal-based food products in HCMC represent a major reservoir of ESBL/pAmpC producing E. coli. PMID- 26989693 TI - Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential. AB - Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity. PMID- 26989694 TI - Quiescent and Active Tear Protein Profiles to Predict Vernal Keratoconjunctivitis Reactivation. AB - OBJECTIVE: Vernal keratoconjunctivitis (VKC) is a chronic recurrent bilateral inflammation of the conjunctiva associated with atopy. Several inflammatory and tissue remodeling factors contribute to VKC disease. The aim is to provide a chip based protein analysis in tears from patients suffering from quiescent or active VKC. METHODS: This study cohort included 16 consecutive patients with VKC and 10 controls. Participants were subjected to clinical assessment of ocular surface and tear sampling. Total protein quantification, total protein sketch, and protein array (sixty protein candidates) were evaluated. RESULTS: An overall increased Fluorescent Intensity expression was observed in VKC arrays. Particularly, IL1beta, IL15, IL21, Eotaxin2, TACE, MIP1alpha, MIP3alpha, NCAM1, ICAM2, betaNGF, NT4, BDNF, betaFGF, SCF, MMP1, and MMP2 were increased in quiescent VKC. Of those candidates, only IL1beta, IL15, IL21, betaNGF, SCF, MMP2, Eotaxin2, TACE, MIP1alpha, MIP3alpha, NCAM1, and ICAM2 were increased in both active and quiescent VKC. Finally, NT4, betaFGF, and MMP1 were highly increased in active VKC. CONCLUSION: A distinct "protein tear-print" characterizes VKC activity, confirming some previously reported factors and highlighting some new candidates common to quiescent and active states. Those candidates expressed in quiescent VKC might be considered as predictive indicators of VKC reactivation and/or exacerbation out-of-season. PMID- 26989695 TI - Ischemic Stroke and Its Risk Factors in a Registry-Based Large Cross-Sectional Diabetic Cohort in a Country Facing a Diabetes Epidemic. AB - The main aim of this study is to determine the prevalence and risk factors of ischemic stroke among diabetic patients registered in the Saudi National Diabetes Registry (SNDR) database. A cross-sectional sample of 62,681 diabetic patients aged >=25 years was used to calculate ischemic stroke prevalence and its risk factors. Univariate and multivariate logistic regression analyses were used to assess the roles of different risk factors. The prevalence of ischemic stroke was 4.42% and was higher in the older age group with longer diabetes duration. Poor glycemic control and the presence of chronic diabetes complications were associated with a high risk of ischemic stroke. History of smoking and type 2 diabetes were more frequent among stroke patients. Obesity significantly decreased the risk for ischemic stroke. Regression analysis for ischemic stroke risk factors proved that age >=45 years, male gender, hypertension, coronary artery disease (CAD), diabetes duration >=10 years, insulin use, and hyperlipidemia were significant independent risk factors for ischemic stroke. We conclude that ischemic stroke is prevalent among diabetic individuals, particularly among those with type 2 diabetes. Good glycemic, hypertension, and hyperlipidemia control, in addition to smoking cessation, are the cornerstones to achieve a significant reduction in ischemic stroke risk. PMID- 26989696 TI - Curcumin Protects Neonatal Rat Cardiomyocytes against High Glucose-Induced Apoptosis via PI3K/Akt Signalling Pathway. AB - The function of curcumin on NADPH oxidase-related ROS production and cardiac apoptosis, together with the modulation of protein signalling pathways, was investigated in cardiomyocytes. Primary cultures of neonatal rat cardiomyocytes were exposed to 30 mmol/L high glucose with or without curcumin. Cell viability, apoptosis, superoxide formation, the expression of NADPH oxidase subunits, and potential regulatory molecules, Akt and GSK-3beta, were assessed in cardiomyocytes. Cardiomyocytes exposure to high glucose led to an increase in both cell apoptosis and intracellular ROS levels, which were strongly prevented by curcumin treatment (10 MUM). In addition, treatment with curcumin remarkably suppressed the increased activity of Rac1, as well as the enhanced expression of gp91(phox) and p47(phox) induced by high glucose. Lipid peroxidation and SOD were reversed in the presence of curcumin. Furthermore, curcumin treatment markedly inhibited the reduced Bcl-2/Bax ratio elicited by high glucose exposure. Moreover, curcumin significantly increased Akt and GSK-3beta phosphorylation in cardiomyocytes treated with high glucose. In addition, LY294002 blocked the effects of curcumin on cardiomyocytes exposure to high glucose. In conclusion, these results demonstrated that curcumin attenuated high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH-mediated oxidative stress and this protective effect is most likely mediated by PI3K/Akt-related signalling pathway. PMID- 26989697 TI - The Association between HbA1c and Cardiovascular Disease Markers in a Remote Indigenous Australian Community with and without Diagnosed Diabetes. AB - OBJECTIVES: This study investigates the burden of cardiovascular risk markers in people with and without diabetes in a remote Indigenous Australian community, based on their HbA1c concentration. METHODS: This study included health screening exams of 1187 remote Indigenous residents over 15 years old who represented 70% of the age-eligible community. The participants were stratified by HbA1c into 5 groups using cut-off points recommended by international organisations. The associations of traditional cardiovascular risk markers with HbA1c groups were assessed using logistic and linear regressions and ANOVA models. RESULTS: Of the 1187 participants, 158 (13%) had a previous diabetes diagnosis, up to 568 (48%) were at high risk (5.7-6.4% (39-46 mmol/mol) HbA1c), and 67 (6%) potential new cases of diabetes (>=6.5% (48 mmol/mol)) were identified. Individuals with higher HbA1c levels were more likely to have albuminuria (OR 3.14, 95% CI 1.26-7.82) and dyslipidaemia (OR 2.37, 95% CI 1.29-4.34) and visited the clinic more often (OR 2.52, 95% CI 1.26-4.99). Almost all traditional CVD risk factors showed a positive association with HbA1c. CONCLUSIONS: Screening in this remote Indigenous Australian community highlights the high proportion of individuals who are at high risk of diabetes as indicated by HbA1c and who also had an accentuated cardiovascular risk profile. PMID- 26989698 TI - Diabetic Endothelium Dysfunction, Cardiovascular Complications, and Therapeutics. PMID- 26989699 TI - Group B Streptococcus Induces a Robust IFN-gamma Response by CD4(+) T Cells in an In Vitro and In Vivo Model. AB - Group B Streptococcus (GBS) serotype III causes life-threatening infections. Cytokines have emerged as important players for the control of disease, particularly IFN-gamma. Although potential sources of this cytokine have been proposed, no specific cell line has ever been described as a leading contributor. In this study, CD4(+) T cell activation profiles in response to GBS were evaluated through in vivo, ex vivo, and in vitro approaches. Total splenocytes readily produce a type 1 proinflammatory response by releasing IFN-gamma, TNF alpha, and IL-6 and actively recruit T cells via chemokines like CXCL9, CXCL10, and CCL3. Responding CD4(+) T cells differentiate into Th1 cells producing large amounts of IFN-gamma, TNF-alpha, and IL-2. In vitro studies using dendritic cell and CD4(+) T cell cocultures infected with wild-type GBS or a nonencapsulated mutant suggested that GBS capsular polysaccharide, one of the major bacterial virulence factors, differentially modulates surface expression of CD69 and IFN gamma production. Overall, CD4(+) T cells are important producers of IFN-gamma and might thus influence the course of GBS infection through the expression balance of this cytokine. PMID- 26989701 TI - Molecular cloning and expression of Cro s 1: an occupational allergen from saffron pollen (Crocus sativus). AB - BACKGROUND: The cultivation of saffron is expanding through the southeast of Iran, and allergy to saffron pollen occurs in workers involved in processing this plant. We aimed to clone, sequence and express a major allergen involved in saffron pollen allergy, and to compare the recombinant with the natural allergen. METHODS: The N-terminal amino acid sequence of Cro s 1, an allergen from saffron pollen, was determined after immunoblotting. The cDNA encoding for this allergen was cloned by PCR utilizing a primer based on the N-terminal amino acid sequence. Recombinant Cro s 1 (rCro s 1) was expressed as a soluble protein in Pichia pastoris and purified to homogeneity by gel filtration. Inhibition of IgE binding to rCro s 1 by pollen extract was analyzed by ELISA. SECTION TITLE: The allergen Cro s 1 was identified from saffron pollen extracts and cloned by PCR. Cro s 1 cDNA defined an acidic polypeptide with homology to pollen proteins from Chenopodium album and Ligastrum vulgaris. The rCro s 1 was expressed in P. pastoris at 28 mg/l. Saffron pollen extract inhibited the binding of patient serum IgE to rCro s 1. CONCLUSION: We identified and cloned the first Crocus sativus pollen allergen. rCro s 1 cDNA shows a very high homology with Che a 1, the major allergen of lamb's-quarter, Chenopodium album, Caryophyllales, pollen (97%). Cro s 1 is a useful tool for specific diagnosis and structural studies of occupational allergy to saffron. PMID- 26989700 TI - Slight Pro-Inflammatory Immunomodulation Properties of Dendritic Cells by Gardnerella vaginalis: The "Invisible Man" of Bacterial Vaginosis? AB - Bacterial vaginosis (BV), the most common genital infection in reproductive-aged women, is associated with increased risk of sexually transmitted infections. Its etiology remains unclear, especially the role of Gardnerella (G.) vaginalis, an anaerobic bacterium characteristic of the BV-alteration of the vaginal ecosystem. In the genital mucosa, dendritic cells (DCs) sense bacteria of the microenvironment via receptors and then orchestrate the immune response by induction of different T cell subtypes. We investigated the interactions between G. vaginalis and human monocyte-derived DCs using a wide range of bacterial concentrations (multiplicity of infection from 0.01 to 100), and the effects of this pathogen on PHA-induced lymphocyte proliferation. As observed by electron microscopy and cytometry, G. vaginalis reduced the internalization ability of DCs by forming extracellular clusters and induced neither DC maturation, nor DC secretion of cytokines, except at the highest dose with a very early DC maturation state. The same profile was observed on lymphocytes with significant increases of proliferation and cytokine secretion only at the highest bacterial concentration. Our findings indicate that G. vaginalis possesses slight immune stimulating activities against DCs and T cells, reflecting thus a defective inflammatory response and giving rise to the atypical, non- or low-grade, inflammatory clinical disease profile. PMID- 26989702 TI - Microbial-resistant Salmonella enteritidis isolated from poultry samples. AB - BACKGROUND: Multidrug resistance in Salmonella enteritidis isolates is a public health problem worldwide; the present study, therefore, was designed for antimicrobial-resistance determination in this strain. METHODS: Salmonella strains isolated from poultry samples by biochemical positive and negative tests were subjected to PCR and identified as Salmonella enteritidis. For detection and identification of Salmonella enteritidis isolates, sdfI gene-specific primers were used. RESULTS: We found that 100% of isolates were resistant to ampicillin, 90% were resistant to cephalothin and streptomycin, 70% were resistant to cefotaxime, and 60% were resistant to kanamycin and gentamicin. CONCLUSION: Salmonella enteritidis isolates had antimicrobial resistance to mentioned antibiotics. PMID- 26989703 TI - Validity of using recombinant melon profilin, Cuc m 2, for diagnosis of melon allergy. AB - BACKGROUND: Allergy is a clinical disorder affecting humans worldwide. Allergenic extracts prepared from natural source materials remain heterogeneous in composition and content, but are regularly used for diagnosis and immunotherapy. Recombinant allergens are suitable candidates to use in place of natural allergens; however, the recombinant allergens should be assessed and compared with the natural ones. Cuc m 2 (profilin), one of the most important allergens of melon (Cucumis melo), has been cloned and was expressed in Escherichia coli (E. coli). We aimed to evaluate the validity of recombinant Cuc m 2 (rCuc m 2) in the diagnosis of melon allergy and investigate whether rCuc m 2 could be used as a replacement for natural Cuc m 2 (nCuc m 2). METHODS: nCuc m 2 was purified by immuno-affinity chromatography and rCuc m 2 was purified by metal-affinity chromatography. SDS-PAGE and western blotting were carried out to evaluate the purification methods. Skin prick tests (SPT), and enzyme immunoassays to determine specific IgE, were performed with the natural and recombinant purified allergens on 53 patients with melon allergy. RESULTS: rCuc m 2 elicited no significantly different responses in skin compared with nCuc m 2. All patients' sera showed similar ODs in ELISAs with natural and recombinant profilin. CONCLUSION: rCuc m 2 evoked strong immuno-reactivity equivalent to nCuc m 2, and has potential for diagnosis of melon allergy. PMID- 26989704 TI - Investigation of DNA integration into reproductive organs following intramuscular injection of DNA in mice. AB - BACKGROUND: DNA immunization with plasmid DNA encoding bacterial, viral, parasitic, and tumor antigens has been reported to trigger protective immunity. The use of plasmid DNA vaccinations against many diseases has produced promising results in animal and human clinical trials; however, safety concerns about the use of DNA vaccines exist, such as the possibility of integration into the host genome, and elicitation of adverse immune responses. METHODS: In this study, we examined the potential integration and bio-distribution of pcDNA3.1+PA, a new vaccine candidate with GenBank accession # EF550208, encoding the PA63 gene, in reproductive organs of mice; ovaries and uterus in female, and testis in male. Animals of both sexes were injected intramuscularly with pcDNA3.1+PA. Host genome integration and tissue distribution were examined using PCR and RT-PCR two times monthly for six months. RESULTS: RT-PCR confirmed that pcDNA3.1+PA was not integrated into the host genome and did not enter reproductive organs. CONCLUSIONS: This finding has important implications for the use of pcDNA3.1+PA plasmid as a vaccine and opens new perspectives in the DNA vaccine area. PMID- 26989705 TI - Cloning and expression of cyclophilin from Platanus orientalis pollens in Escherichia coli. AB - BACKGROUND: Allergy is a clinical disorder affecting the human population with wide geographical distribution. Platanus orientalis (P. orientalis) trees are planted in many countries and their pollen causes allergic reactions. Cyclophilin has recently been identified as one of the most important allergens of P. orientalis pollen. We aimed to clone and purify this allergen in Escherichia coli for further studies and therapeutic and diagnostic purposes for allergy to P. orientalis . METHODS: RNA was extracted from P. orientalis. A full-length fragment encoding cyclophilin was prepared by polymerase chain reaction amplification of the first-strand cDNA synthesized from P. orientalis RNA. The cDNA was inserted into the pET32b (+) vector, and the construct transformed into E. coli Top10 and BL21 cells. The expressed protein was purified by the CuSO4 method. RESULTS: The cDNA for the cyclophilin of P. orientalis pollen was cloned, and a specific reactivity of recombinant cyclophin was confirmed by immunoblotting using sera from patients allergic to P. orientalis pollen. CONCLUSION: The recombinant cyclophilin has a potential for immunologic assays for evaluation of allergy to P. orientalis pollen. PMID- 26989706 TI - Decreased levels of soluble Toll-like Receptor 2 in patients with asthma. AB - BACKGROUND: Recently, reports have indicated a role for the membrane form of Toll like Receptor 2 (TLR2) in asthma pathogenesis. In this study we examined soluble TLR2 levels in serum and sputum of asthmatic and healthy subjects. METHODS: Serum and sputum samples were obtained from 33 asthmatic and 19 healthy subjects. The asthmatics were classified into four groups according to the Global Initiative for Asthma. A sandwich ELISA was developed to measure soluble TLR2 (sTLR2) in serum and sputum. TLR2 mRNA expression was determined by semi-quantitative RT-PCR of all sputum samples. RESULTS: The mean sTLR2 levels from serum and sputum of asthmatics were significantly lower than those from healthy subjects. Moreover, sTLR2 concentration decreased concomitantly with asthma severity. The differences observed, however, were not statistically significant. TLR2/GAPDH mRNA of sputum leukocytes was also significantly lower in asthmatics than in healthy subjects. CONCLUSION: This study demonstrated for the first time thatsTLR2 levels are lower in serum and sputum samples from asthmatic than from healthy subjects, and this could be an indicator of TLR2 expression. We also found that sTLR2 concentration in serum decreased concomitantly with an increase of asthma severity clinical score . PMID- 26989707 TI - The evaluation of food allergy on behavior in autistic children. AB - BACKGROUND: Despite many efforts, the etiology of autism remains unknown. Food allergy has been suggested as a pathogenic factor in Autism Spectrum Disorder (ASD). Our aim in this study was to determine whether food allergy could be considered as a risk factor for autistic children. METHODS: Thirty-nine autistic children were examined by the skin prick test (SPT), and total serum IgE was evaluated by ELISA. SPTs were performed for egg whites, oranges, peanuts, tomatoes, tuna fish, walnuts, aubergines, melons, grapes, and cow milk. Parents and teachers were then asked to exclude these items from the childrens' diets for six months. After the treatment period, the autistic children who tested positive for food allergies were re-assessed by a standard questionnaire to obtain further information about their medical histories. RESULTS: Three of the study's 39 autistic children (7.7%) tested positive on the SPT. Total serum IgE levels were elevated in 56.4% of the subjects (mean=164+/-24.5, cut-off >155 IU/ml). The results showed a decreased mean in the childrens' autistic behaviors on the Children Autism Rating Scale (CARS) after both eight weeks and six months; however, this decrease was not statistically significant. CONCLUSION: Food allergy may play a role in the pathophysiology of autism. We conclude that avoidance of certain foods benefits the behavior of autistic children. PMID- 26989708 TI - Comparison of Th1 and Th2 responses in non-healing and healing patients with cutaneous leishmaniasis. AB - BACKGROUND: Cutaneous leishmaniasis is an endemic disease in many regions of Iran, including the city of Mashhad. In recent years, some cases have not responded to Glucantime, the usual treatment for this disease. The cellular immune response caused by T-helper type 1 (Th1) cells has an important role in protection against leishmaniasis, and activation of the T-helper type 2 (Th2) response causes progression of the disease. By analyzing these responses we hope to find a more effective treatment than that currently in use for leishmaniasis patients. METHODS: The cellular immune responses in 60 cases of non-healing and healing cutaneous leishmaniasis, and individuals in a control group, were analyzed by measuring cytokines released by peripheral blood mononuclear cells (PBMCs) when stimulated with Leishmania major antigens by Enzyme Linked Immuno Sorbent Assay (ELISA). RESULTS: Subjects from the healing group secreted more interleukin-12 (IL-12) and interferon gamma (IFN-gamma) (p<0.05) and less interleukins -4, -5, -10 (IL-4, IL-5, and IL-10) (p<0.005) and -18 (IL-18) (p=0.003) than the non-healing group. CONCLUSIONS: The results demonstrate that secretion of cytokines that activate Th2 response including IL-4, IL-5 and IL-10 in non-healing subjects was higher than healing subjects and secretion of cytokines that activate Th1 response including IL-12 and IFN-gamma in healing subjects was higher relative to the non-healing subjects. In this study it has been shown that the level of IL-18 progresses disease in non-healing patients when the level of IL-12 gets decreased. PMID- 26989709 TI - Molecular cloning, characterization, and expression of Cuc m 2, a major allergen in Cucumis melo. AB - BACKGROUND: Several studies reported the clinical features of IgE-mediated hypersensitivity after ingestion of melon. Melon allergy is a common IgE-mediated fruit allergy in Iran. This prompted us to investigate immunochemical and molecular properties of the major allergen in melon fruit, to compare the IgE binding capacity of the natural protein with the recombinant allergen, and to determine cross-reactivity of the major allergen with closely-related allergens from other plants displaying clinical cross-reactivity with melon. METHODS: Identification and molecular characterization of the major melon allergen were performed using IgE immunoblotting, allergen-specific ELISA, affinity-based purifications, cross-inhibition assays, cloning, and expression of the allergen in Escherichia coli. RESULTS: Melon profilin was identified and isolated as a major IgE-binding component and designated as Cuc m 2. Sequencing corresponding cDNA revealed an open reading frame of 363 bp coding for 131 amino acid residues and two fragments of 171 bp and 383 bps for the 5'and 3' UTRs, respectively. Significant cross-reactivity was found between melon profilin and Cynodon dactylon, tomato, peach, and grape profilins in cross-inhibition assays. Although the highest degree of amino acid identity was revealed with watermelon profilin, there was no significant cross-reactivity between melon and watermelon profilins. CONCLUSION: Melon profilin is the major IgE-binding component in melon extract, and the recombinant and natural forms exhibited similar IgE-binding capacities. A part of the fruit-fruit and pollen-fruit cross-reactions could be explained by the presence of this conserved protein; however, sequence homology provides insufficient information to predict IgE cross-reactivity of profilins. PMID- 26989710 TI - Relation of type 2 diabetes mellitus with gender, education, and marital status in an Iranian urban population. AB - BACKGROUND: Type 2 diabetes mellitus is one of the most important cardiovascular risk factors. OBJECTIVES: This study was performed to assess the relationship of diabetes with gender, education, and marital status in an Iranian urban population. METHODS: A total of 892 men and women aged 30-85 were recruited using a cluster-stratified sampling method from an urban population. Using a questionnaire, demographical data including gender, education, and marital status were collected. A blood sample after fasting for at least eight hours was collected from each subject. Associations of type 2 diabetes mellitus and studied variables were tested for significance. RESULTS: The prevalence of diabetes mellitus was 11.6%; 11.1% in men and 12.1% in women with no significant difference between them. Diabetes mellitus was most prevalent in the oldest age (age more than 60 years, 22.9%) and low education groups (17.9%, P < 0.001). Marital status was not significantly related to diabetes mellitus (P= 0.37). CONCLUSION: The prevalence of diabetes mellitus is related to education within the Iranian population. Thus preventive strategies should be based on the affective factors. PMID- 26989711 TI - Identification of Leishmania species causing cutaneous leishmaniasis using Random Amplified Polymorphic DNA (RAPD-PCR) in Kharve, Iran. AB - BACKGROUND: Leishmaniasis, especially cutaneous leishmaniasis, is considered an important health problem in many parts of Iran including Kharve, Khorasan Razavi province. Cutaneous leishmaniasis is caused by various species of Leishmania, each having a different secondary host. Thus, identifying the parasites' specie is of paramount importance for containment strategy planning. The morphological differentiation of Leishmania species is not possible, rendering the molecular methods as the sole means to this purpose. Therefore, to identify the causative agent of cutaneous leishmaniasis in Kharve, Random Amplified Polymorphic DNA-PCR (RAPD-PCR) was used. METHODS: The disease was first confirmed by direct smears. Samples were gathered from 22 patients with established cutaneous leishmaniasis. The samples were immediately cultured in NNN medium, followed by sub-culture in RPMI-1640. Afterwards, DNA was extracted and amplified using RAPD-PCR. Electrophoresis patterns from each isolate were compared with reference strains of Leishmania major (L. major) and Leishmania tropica (L. tropica). RESULTS: The results of this study indicated that the parasite causing cutaneous leishmaniasis in Kharve is L. tropica. CONCLUSION: It seems that L. tropica is the only causative agent of cutaneous leishmaniasis in Kharve, and RAPD-PCR is a suitable tool for Leishmania characterization in epidemiological studies. PMID- 26989712 TI - The role of anti-CCD antibodies in grape allergy diagnosis. AB - BACKGROUND: Allergens are mostly composed of glycoprotein structures. It is believed that glycan-specific antibodies may lead to false-positive reactions in immunoassays. In this study we investigated the glycosylation state of grape allergens as well as the presence of antibodies to cross-reactive carbohydrate determinants (anti-CCDs) in sera from grape-sensitive individuals. METHODS: Grape extract proteins were electrotransferred onto PVDF membranes and their glycosylation states were analyzed by blotting methods. To assess the presence of anti-CCDs, natural and mildly deglycosylated proteins were immunoblotted with grape-allergic subjects' sera. We also measured the IgE reactivity of each subject's sera with other fruit extracts via an indirect ELISA. RESULTS: Immunoblotting studies showed that mildly deglycosylated grape proteins had lower IgE-binding capacity than their intact natural counterparts, which could be due to the presence of anti-CCDs. Biotinylation studies confirmed that the glycosylation levels of the 24, 32, and 60 kDa IgE-reactive proteins were higher than those of the 38 and 45 kDa ones. Lectin blotting showed that the 24 and 60 kDa bands were highly mannosylated, with the highest level of mannosylation on the 24 kDa allergen. CONCLUSION: This study showed that some grape allergens are glycosylated and that anti-CCD antibodies may cause weakly false-positive results during assessment of IgE reactivity to grape allergens. PMID- 26989713 TI - Construction of an expression plasmid (vector) encoding Brucella melitensis outer membrane protein, a candidate for DNA vaccine. AB - BACKGROUND: DNA vaccination with plasmid encoding bacterial, viral, and parasitic immunogens has been shown to be an attractive method to induce efficient immune responses. Bacteria of the genus Brucella are facultative intracellular pathogens for which new and efficient vaccines are needed. METHODS: To evaluate the use of a DNA immunization strategy for protection against brucellosis, a plasmid containing the DNA encoding the Brucella melitensis (B. melitensis) 31 kDa outer membrane protein, as a potent immunogenic target, was constructed. RESULTS: The constructed plasmid, pcDNA3.1+omp31, was injected intramuscularly into mice and the expression of omp31 RNA was assessed by RT-PCR. The integrity of the pcDNA3.1+omp31 construct was confirmed with restriction analysis and sequencing. Omp31 mRNA expression was verified by RT-PCR. CONCLUSION: Our results indicate that the pcDNA3.1+omp31 eukaryotic expression vector expresses omp31 mRNA and could be useful as a vaccine candidate. PMID- 26989714 TI - Partial distal 10q trisomy due to de novo amplification: A new case without furrows or ridges in fingers and palms. AB - BACKGROUND: Here we describe a new case of partial distal 10q trisomy in a 6-year old Iranian girl from healthy parents with mental, growth, and psychomotor retardations. METHODS: Additional clinical features include dysmorphic craniofacial features, microcephaly, bilateral hydronephrosis without heart problems, small and rotated low-set ears, bow-shaped mouth, abnormal teeth, short neck, and as a first case reported, fingers with camptodactly (i.e., without any furrows or ridges in the palms and fingers). RESULTS: Cytogenetic analysis (GTG banding) revealed an unbalanced female karyotype with additional bands at the end of the long arm of chromosome 10, karyotype: 46,XX,dup(10)(q25q26). CONCLUSION: According to the banding pattern it is most likely that a duplication of the distal part of the long arm of chromosome 10 occurred. PMID- 26989715 TI - Familial resemblance of body composition, physical activity, and resting metabolic rate in pre-school children. AB - BACKGROUND: Although parental obesity is a well-established predisposing factor for the development of obesity, associations between regional body compositions, resting metabolic rates (RMR), and physical activity (PA) of parents and their pre-school children remain unknown. The objective of this study was to investigate parent-child correlations for total and regional body compositions, resting energy expenditures, and physical activity. METHODS: Participants were 89 children aged 2-6 years and their parents, consisting of 61 families. Resting metabolic rate was assessed using indirect calorimetry. Total and regional body compositions were measured by both dual energy X-ray absorptiometry (DXA) and deuterium dilution. Physical activity was assessed by an accelerometer. RESULTS: There was a significant parent-offspring regression for total fat free mass (FFM) between children and their mothers (P=0.02), fathers (P=0.02), and mid-parent (average of father and mother value) (P=0.002) when measured by DXA. The same was true for fat mass (FM) between children and mothers (P<0.01), fathers (P=0.02), and mid-parent (P=0.001). There was no significant association between children and parents for physical activity during the entire week, weekend, weekdays, and different parts of days, except for morning activity, which was positively related to the mothers' morning activities (P<0.01) and mid-parent (P=0.009). No association was found between RMR of children and parents before and after correction for FFM and FM. CONCLUSION: These data suggest a familial resemblance for total body composition between children and their parents. Our data showed no familial resemblance for PA and RMR between children and their parents. PMID- 26989716 TI - Construction of a recombinant allergen-producing probiotic bacterial strain: Introduction of a new line for a live oral vaccine against Chenopodium album pollen allergy. AB - BACKGROUND: During the last two decades, significant advances have been made in the fields of lactococcal genetics and protein expression. Lactococcus lactis (L. lactis) is an effective vector for protein expression and can be used as an antigen delivery system. Hence, L. lactis is an ideal candidate for mucosal immunotherapy. Profilin (Che a 2), the major allergen in Chenopodium album, is one of the most important causes of allergic diseases in desert and semi-desert areas, especially in Iran, Saudi Arabia, and Kuwait that was cloned and expressed in L. lactis for the first time. METHODS: To construct L. lactis that expressed Che a 2, a DNA sequence was cloned and used to transform bacteria. Expression of Che a 2 was analyzed via monitoring of related RNA and protein. Hydrophobicity, adherence to HT-29 cells, antibiotic resistance, resistance to gastrointestinal contents, pH, and bile salt in recombinant and native L. lactis were evaluated. RESULTS: Immunoblot analyses demonstrated that recombinant Che a 2 is expressed as a 32 kDa dimeric protein immunological studies showed it can bind human IgE. Both native and recombinant bacteria were sensitive to low pH and simulated gastric conditions. Bacterial survival was reduced 80-100% after 2 h of exposure to pH 1.5-2. Both native and recombinant bacteria were able to grow in 0.3 and 2% bile salts. After incubation of recombinant L. lactis in simulated gastric and intestinal juices for one and two hours, respectively, cell survival was reduced by 100%. Adhesion capability in both strains was minimal and there were no significant differences in any of our tests between native and recombinant bacteria. CONCLUSION: Successfully recombinant L. lactis with capability of expression Che a 2 was produced and revealed it is sensitive to gastrointestinal contents. PMID- 26989717 TI - Construction and eukaryotic expression of recombinant large hepatitis delta antigen. AB - BACKGROUND: Hepatitis delta virus (HDV) is a subviral human pathogen that exploits host RNA editing activity to produce two essential forms of the sole viral protein, hepatitis delta antigen (HDAg). Editing at the amber/W site of HDV antigenomic RNA leads to the production of the large form (L-HDAg), which is required for RNA packaging. METHODS: In this study, PCR-based site-directed mutagenesis by the overlap extension method was used to create the point mutation converting the small-HDAg (S-HDAg) stop codon to a tryptophan codon through three stages. RESULTS: Sequencing confirmed the desirable mutation and integrity of the L-HDAg open reading frame. The amplicon was ligated into pcDNA3.1 and transfected to Huh7 and HEK 293 cell lines. Western blot analysis using enhanced chemiluminescence confirmed L-HDAg expression. The recombinant L-HDAg localized within the nuclei of cells as determined by immunofluorescence and confocal microscopy. CONCLUSION: Because L-HDAg requires extensive post-translational modifications, the recombinant protein expressed in a mammalian system might be fully functional and applicable as a tool in HDV molecular studies, as well as in future vaccine research. PMID- 26989718 TI - Construction of eukaryotic expression vectors encoding CFP-10 and ESAT-6 genes and their potential in lymphocyte proliferation. AB - BACKGROUND: Mycobacterium (M.) bovis is the agent of bovine tuberculosis (TB) in a range of animal species, including humans. Recent advances in immunology and the molecular biology of Mycobacterium have allowed identification of a large number of antigens with the potential for the development of a new TB vaccine. The ESAT-6 and CFP-10 proteins of M. bovis are important structural and functional proteins known to be important immunogens. METHODS: In the current study, the DNAs encoding these genes were utilized in the construction of pcDNA 3.1+/ESAT-6 and pcDNA3.1+/CFP-10 plasmids. After intramuscular injection of BALB/c mice with these plasmids, ESAT-6 and CFP-10 mRNA expression was assessed by RT-PCR. Mice were inoculated and boosted with the plasmids to evaluate their effects on lymphocyte proliferation. RESULTS: Our results indicate the plasmids are expressed at the RNA level and can induce lymphocyte proliferation. CONCLUSION: Further study is needed to characterize the effect of these antigens on the immune system and determine whether they are effective vaccine candidates against M. bovis. PMID- 26989719 TI - Quantification and optimization of Candida albicans DNA in blood samples using Real- Time PCR. AB - BACKGROUND: Candida albicans (C. albicans) is a major cause of candidaemia in people with impaired immunity. Blood culture is a "gold standard" for candidaemia detection but is time-consuming and relatively insensitive. We established a real time PCR assay for C. albicans detection in blood by LightCycler PCR and melting curve analysis. METHODS: Five milliliter blood samples from healthy volunteers were spiked with 10(0)-10(6) C. albicans cells to determine the detection limit of our method. DNA was extracted from whole blood using glass beads and the QIAamp DNA Blood Mini Kit (Qiagen, Hilden Germany). DNA from C. albicans isolates were amplified with primers and inserted into Escherichia coli (E. coli) DH5alpha.1 cells with the TA cloning vector (Invitrogen). The plasmid was used for standardization and optimization. A quantitative PCR assay with the LightCycler amplification and detection system based on fluorescence resonance energy transfer (FRET) with two different specific probes was established. To assess the precision and reproducibility of real-time PCR the intra-assay precision was determined in six consecutive assays. RESULTS: No cross-reactivity of the hybridization probes with the DNA of non-C. albicans species or human genomic DNA was observed, which confirmed its 100% specificity. The minimum limit detected was one C. albicans cell or 10(0) CFU/ml (10 fg) per PCR reaction. The real-time PCR efficiency rate for Candida was high (E = 1.95). Melting curve analysis of C. albicans showed a specific melting peak temperature of 65.76 degrees C. CONCLUSION: The real-time PCR assay we developed is highly specific and sufficiently sensitive to detect the fungal load for early diagnosis of invasive candidiasis. PMID- 26989720 TI - Hepatitis E virus and serum level aminotransferases in blood donors. AB - BACKGROUND: Hepatitis E virus (HEV) infection is a self-limiting viral infection that can lead to severe complications and death. In different regions the epidemiology of this infection varies. In this study we evaluated the seroepidemiology of hepatitis E infection in Jahrom, a city in southern Iran. METHODS: This was a cross-sectional descriptive study of serum samples from 477 subjects, including 30 females and 447 males. HEV immunoglobulin G (IgG) and immunoglobulin M (IgM) were measured by enzyme-linked immunosorbent assays (ELISA). Alanine transaminase (ALT) and aspartate transaminase (AST) levels were also determined. Four hundred forty-seven subjects were male and 30 were female. Subjects were classified by age and sex. RESULTS: One woman (3.3%) and 25 men (5.5%) were positive for HEV antibodies (IgG and/or IgM). There was found an association between serum level of aminotransferases and seropositivity for HEV. CONCLUSION: The result of this study indicates that HEV is an etiological factor for hepatitis in this area of IRAN. The cost benefit of active immunization in endemic regions should be evaluated because an outbreak could have tragic consequences. PMID- 26989721 TI - A genetic assay of three patients in the same family with Holt-Oram syndrome; a case report. AB - Holt-Oram syndrome (HOS) is a developmental disorder inherited in an autosomal dominant pattern. Affected organs are the heart and forelimbs with upper extremity skeletal defects and congenital heart malformation. In this study we present three cases of HOS in the same family. In one of these three individuals we detected a transition of C to T (CTG-GTT, V205V) in exon 7 of the TBX5 gene. This nucleotide change causes no amino acid change and potential pathologic effects remain unknown. PMID- 26989722 TI - Simulation of Major Histocompatibility Complex (MHC) structure and peptide loading into an MHC binding pocket with teachers'hands. AB - Molecular understanding of three-dimensional (3D) peptide: MHC models require both basic knowledge of computational modeling and skilled visual perception, which are not possessed by all students. The present model aims to simulate MHC molecular structure with the hands and make a profound impression on the students. PMID- 26989723 TI - Vascular endothelial growth factor from embryonic status to cardiovascular pathology. AB - Vascular endothelial growth factor (VEGF) is a multifunctional cytokine with distinct functions in angiogenesis, lymphangiogenesis, vascular permeability, and hematopoiesis. VEGF is a highly conserved, disulfide-bonded dimeric glycoprotein of 34 to 45 kDa produced by several cell types including fibroblasts, neutrophils, endothelial cells, and peripheral blood mononuclear cells, particularly T lymphocytes and macrophages. Six VEGF isoforms are generated as a result of alternative splicing from a single VEGF gene, consisting of 121, 145, 165, 183, 189, or 206 amino acids. VEGF121, VEGF145, and VEGF165 are secreted whereas VEGF183, VEGF189, and VEGF206 are cell membrane-bound. VEGF145 has a key role during the vascularization of the human ovarian follicle and corpus luteum, in the placentation and embryonic periods, and in bone and wound healing, while VEGF165 is the most abundant and biologically active isoform. VEGF has been linked with a number of vascular pathologies including cardiovascular diseases such ischemic heart disease, heart failure, stroke, and diabetes and its related complications. In this review we aimed to present some important roles of VEGF in a number of clinical issues and indicate its involvement in several phenomena from the initial steps of the embryonic period to cardiovascular diseases. PMID- 26989724 TI - A study of lipid- and protein- bound sialic acids for the diagnosis of bladder cancer and their relationships with the severity of malignancy. AB - BACKGROUND: The gold standard for detection of bladder cancer is cystoscopy, which is an invasive and complicated procedure. Our study was conducted to find a tumor marker with high specificity, sensitivity, and accuracy for the diagnosis of bladder cancer. METHODS: Serum samples were collected from 58 bladder cancer patients and 60 healthy control subjects. Levels of lipid-bound sialic acid (LBSA), and protein-bound sialic acid (PBSA) were measured spectrophotometrically by Aminoff's method. RESULTS: Mean levels of both markers were found to be significantly higher in the patients than the healthy controls. Positive correlations were observed between serum levels of lipid- (r=0.283, p<0.05) and protein- bound (r=0.56, p<0.05) sialic acids and the grade of malignancy. To differentiate patients with bladder tumors from healthy controls, cut-offpoints were determined for each of the two parameters based on Receiver Operating Characteristic (ROC) curve analysis (LBSA=21.25 mg/dL, PBSA=6.15 mg/dL). The data showed good sensitivities (LBSA=89%, PBSA=79%), specificities (LBSA=70%, PBSA=70%) and accuracies (LBSA=83%, PBSA=81%) for both markers. CONCLUSION: Measuring serum LBSA and PBSA by this simple, reproducible, noninvasive, and inexpensive method can accurately discriminate cancer patients from healthy individuals. PMID- 26989725 TI - Inherited genetic markers for thrombophilia in northeastern Iran (a clinical based report). AB - BACKGROUND: Thrombophilia is a main predisposition to thrombosis due to a procoagulant state. Several point mutations play key roles in blood-clotting disorders, which are grouped under the term thrombophilia. These thrombophilic mutations are methylenetetrahydrofolate reductase (MTHFR, C677T, and A1298C), factor V Leiden (G1691A), prothrombin gene mutation (factor II, G20210A), and plasminogen activator inhibitor (PAI). In the present study, we assessed the prevalence of the above thrombophilia markers in patients with recurrent pregnancy loss or first and second trimester abortions, infertility, and failed in vitro fertilization (IVF). METHODS: This study was conducted among 457 cases those were referred to detect the inherited genetic markers for thrombophilia. Markers for MTHFR, Factor II, and Factor V were assessed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and PAI was assessed by Amplification Refractory Mutation System (ARMS-PCR). RESULTS: Two hundred sixty cases (56.89%) were diagnosed as having at least one thrombophilia marker, whereas 197 cases (43.11%) had no thrombophilia markers and were normal. CONCLUSION: According to the current study, the pattern of abnormal genetic markers for thrombophilia in northeastern Iran demonstrates the importance of genetic evaluations in patients who show clinical abnormalities with recurrent spontaneous abortion (RSA) or other serious obstetric complications. PMID- 26989726 TI - Identification and molecular characterization of the cDNA encoding Cucumis melo allergen, Cuc m 3, a plant pathogenesis-related protein. AB - BACKGROUND: Melon (Cucumis melo) allergy is one of the most common food allergies, characterized by oral allergy syndrome. To date, two allergen molecules, Cuc m 1 and Cuc m 2, have been fully characterized in melon pulp, but there are few reports about the molecular characteristics of Cuc m 3. METHODS: The Cuc m 3 cDNA has been characterized by rapid amplification of cDNA ends (RACE), which revealed a 456 base-pair (bp) fragment encoding a 151-amino acid polypeptide with a predicted molecular mass of 16.97 kDa, and identified 79 and 178 bp untranslated sequences at the 5' and 3' ends, respectively. RESULTS: In silico analysis showed strong similarities between Cuc m 3 and other plant pathogen-related protein 1s from cucumber, grape, bell pepper, and tomato. CONCLUSION: Here we report the identification and characterization of the Cuc m 3 cDNA, which will be utilized for further analyses of structural and allergenic features of this allergen. PMID- 26989727 TI - Identification of Spata-19 new variant with expression beyond meiotic phase of mouse testis development. AB - BACKGROUND: The study of specific genes expressed in the testis is important to understanding testis development and function. Spermatogenesis is an attractive model for the study of gene expression during germ cell differentiation. Spermatogenesis associated-19 (Spata-19) is a recently-identified important spermatogenesis-related gene specifically expressed in testis. Its protein product is involved in sperm cell development and reproduction. In this report we examined the expression of Spata-19 mRNA in mouse testis, fetus, and cell lines. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), nested PCR, and PCR-restriction fragment length polymorphism (PCR-RFLP) were used to analyze Spata-19 mRNA expression in different stages of mouse testis development, mouse fetus, mouse embryonic fibroblasts (MEF), mouse embryonic stem cells (mESC), Sertoli cells, and NIH/3T3 cells. RESULTS: We identified a novel splice variant of Spata-19 in the mouse genome that it is expressed in the fetus and after the meiotic phase of spermatogenesis, and over-expressed in the post-meiotic stage of mouse spermatogenesis. This novel splice variant was absent in five days old mice testis, mESC, MEF, Sertoli, and NIH/3T3 cell lines. CONCLUSION: The Spata-19 has a large novel splice variant in mouse testis that is expressed beyond meiotic phase of testis development. We suggest that this new Spata-19 mRNA variant might be involved in mitochondrial maintenance in sperm cells, and might be correlated with androgen secretion and male fertility. PMID- 26989728 TI - EBV seroepidemiology in married and unmarried women and men in Iran. AB - BACKGROUND: Among the eight known human herpes viruses, Epstein- Barr virus (EBV) is considered to be sexually transmissible. This study was conducted to evaluate the seroepidemiology of this infection in married and unmarried Iranian couples. METHODS: In this comparative observational and cross-sectional study, 160 men and women were divided into married and unmarried groups. Serum IgG and IgM antibodies to the EBV viral capsid antigen were analyzed by Enzyme-linked Immunosorbent Assays (ELISAs). RESULTS: In this study 78 men and 82 women were enrolled. Ninety percent of the married and 76.2% of the unmarried women were anti-EBV IgG positive (P = 0.08), while 80% of the married and 94% of the unmarried men were antiEBV IgG positive (P = 0.052). CONCLUSION: Seroepidemiology of EBV is not significantly different in married vs. unmarried women and men in Iran; therefore, sexual contact may not be the primary mechanism of EBV transmission in Iran and other developing countries. Attention to other possible routes of transmission is recommended. PMID- 26989729 TI - Recurrent pregnancy loss in a subject with heterozygote factor V Leiden mutation; a case report. AB - Recurrent pregnancy loss is usually defined as the loss of two or more consecutive pregnancies before 20 weeks of gestation, which occurs in approximately 5% of reproductive-aged women. It has been suggested that women with thrombophilia have an increased risk of pregnancy loss and other adverse pregnancy outcomes. Thrombophilia is an important predisposition to blood clot formation and is considered as a significant risk factor for recurrent pregnancy loss. The inherited predisposition to thrombophilia is most often associated with factor V Leiden mutation, prothrombin G20210A mutation, and methylenetetrahydrofolate reductase C677T and A1298C gene variants. The net effect is an increased cleavage of prothrombin to thrombin and excessive blood coagulation. PMID- 26989730 TI - An evolutionary relationship between Stearoyl-CoA Desaturase (SCD) protein sequences involved in fatty acid metabolism. AB - BACKGROUND: Stearoyl-CoA desaturase (SCD) is a key enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs) in fat biosynthesis. Despite being crucial for interpreting SCDs' roles across species, the evolutionary relationship of SCD proteins across species has yet to be elucidated. This study aims to present this evolutionary relationship based on amino acid sequences. METHODS: Using Multiple Sequence Alignment (MSA) and phylogenetic construction methods, a hypothetical evolutionary relationship was generated between the stearoyl-CoA desaturase (SCD) protein sequences between 18 different species. RESULTS: SCD protein sequences from Homo sapiens, Pan troglodytes (chimpanzee), and Pongo abelii (orangutan) have the lowest genetic distances of 0.006 of the 18 species studied. Capra hircus (goat) and Ovis aries (Sheep) had the next lowest genetic distance of 0.023. These farm animals are 99.987% identical at the amino acid level. CONCLUSIONS: The SCD proteins are conserved in these 18 species, and their evolutionary relationships are similar. PMID- 26989731 TI - Geographic heterogeneity of the AML1-ETO fusion gene in Iranian patients with acute myeloid leukemia. AB - BACKGROUND: The human AML1 gene, located on chromosome 21, can be fused to the AML1- eight-twenty-one (ETO) oncoprotein on chromosome eight, resulting in a t(8;21)(q22;q22) translocation. Acute myeloid leukemia (AML) associated with this translocation is considered a distinct AML with a favorable prognosis. Due to the various incidences of the translocation, which is associated with geographic diversities, investigation of molecular epidemiology is important to increase the awareness of physicians and hematologists regarding the frequency this chromosomal aberration. METHODS: The patients were classified according to the French-American-British classification into eight groups: M0-M7. Determination of the prevalence of the AML1-ETO fusion gene was accomplished by TaqMan real-time PCR. Bone marrow samples from 113 patients with newly-diagnosed, untreated AML M1, -M2, and -M4, and 20 healthy controls admitted to the Ghaem Hospital in Mashhad, Iran were studied. RESULTS: The AML1-ETO fusion gene was detected up 50% of the M2 subgroup and absent in the M1 and M4 subtypes and healthy controls. Comparison of the prevalence of the t(8;21) translocation with results of previous studies showed that it varies between countries. This result may be due to geographic or ethnic differences, or both. CONCLUSIONS: The relatively high prevalence of the t(8;21) translocation in Iran was similar to that found in other Asian countries. It was closely associated with female gender, relatively young age, and FAB-M2 subtype. Its distribution varied considerably with geographic area. Therefore, further studies are needed to provide epidemiological data important for the establishment of optimal therapeutic strategies applicable to patients of each region. PMID- 26989732 TI - Amelioration of altered serum, liver, and kidney antioxidant enzymes activities by sodium selenite in alloxan-induced diabetic rats. AB - BACKGROUND: The aim of this study was to evaluate the possible protective effect of sodium selenite on serum, liver, and kidney antioxidant enzymes activities in alloxan-induced type 1 diabetic rats. METHODS: Forty Sprague-Dawley male rats were randomly divided into four groups; Group one as control, Group two as sham treated with sodium selenite by 1 mg/kg intraperitoneal (i.p.) injections daily, Group three as diabetic untreated, and Group four as diabetic treated with sodium selenite by 1 mg/kg i.p. injections daily .Diabetes was induced in the third and fourth groups by subcutaneous alloxan injections. After eight weeks the animals were euthanized and livers and kidneys were immediately removed and used fresh or kept frozen until analysis. Before the rats were killed blood samples were also collected to measure glutathione peroxidase (GPX) and catalase (CAT) activities in sera. RESULTS: Glutathione peroxidase and CAT activities serum, liver, and kidney were all significantly less in the diabetic rats than in the controls. Sodium selenite treatment of the diabetic rats resulted in significant increases in GPX activity in the kidneys and livers, and CAT activity in the sera and livers. CONCLUSIONS: Our results indicate that sodium selenite might be a potent antioxidant that exerts beneficial effects on both GPX and CAT activities in alloxan-induced type 1 diabetic rats. PMID- 26989733 TI - Effects of surface viscoelasticity on cellular responses of endothelial cells. AB - BACKGROUND: One area of nanoscience deals with nanoscopic interactions between nanostructured materials and biological systems. To elucidate the effects of the substrate surface morphology and viscoelasticity on cell proliferation, fractal analysis was performed on endothelial cells cultured on nanocomposite samples based on silicone rubber (SR) and various concentrations of organomodified nanoclay (OC). METHODS: The nanoclay/SR ratio was tailored to enhance cell behavior via changes in sample substrate surface roughness and viscoelasticity. RESULTS: Surface roughness of the cured SR filled with negatively-charged nanosilicate layers had a greater effect than elasticity on cell growth. The surface roughness of SR nanocomposite samples increased with increasing the OC content, leading to enhanced cell growth and extracellular matrix (ECM) remodeling. This was consistent with the decrease in SR segmental motions and damping factor as the primary viscoelastic parameters by the nanosilicate layers with increasing clay concentrations. CONCLUSIONS: The inclusion of clay nanolayers affected the growth and behavior of endothelial cells on microtextured SR. PMID- 26989734 TI - TLR4 and TLR2 expression in biopsy specimens from antral and corporal stomach zones in Helicobacter pylori infections. AB - BACKGROUND: It is not yet known which types of Toll-like receptors (TLRs) are most effective in Helicobacter pylori (H. pylori) recognition. It is also not known which gastric zones have the most prominent roles in TLR-mediated bacterial recognition. The aim of this work was to analyze the expression of TLR2 and TLR4 in biopsy specimens from H. pylori-infected patients. METHODS: Thirty-eight patients with gastrointestinal disorders were divided into four groups in this study. The groups were: (A) H. pylori infection and peptic ulcer (n=15), (B) peptic ulcer only (n=5), (C) H. pylori infection only (n=10) and (D) control, with neither H. pylori infection nor peptic ulcer (n=8). Biopsy specimens from sites of redness or atrophic mucosa from gastric antrum and body in patients with gastritis were collected. RNAs from the antrum and body specimens were isolated. TLR2 and TLR4 mRNA expression was assessed by RT-PCR and quantified as densitometric ratios of TLR2 and TLR4/beta-actin mRNA. RESULTS: In the antral zones of H. pylori-infected patients (Groups A and C) TLR2 and TLR4 expression was significantly greater than in uninfected patients (Groups B and D) regardless of peptic ulcers (p < 0.05). In the gastric body samples TLR2 expression was significantly greater in Group C (H. pylori infection only) than in Group B (peptic ulcer only) and TLR4 expression was significantly greater in group A (H. pylori infection and peptic ulcer) than in Group B (peptic ulcer only) (p < 0.05). No significant differences in expression of TLR4 and TLR2 were observed between samples from the antrum and body in same groups. CONCLUSIONS: We conclude that H. pylori infection leads to significant increase in TLR2 and TLR4 molecules expression in antral region related to the control group. Considering the stimulatory effect of H. pylori on TLRs expression in the gastric tissue, we assume that colonization of H. pylori infection might occurs more in the gastric antral region than in the gastric body. PMID- 26989735 TI - Occult hepatitis B demonstrated by anti-HBc and HBV DNA in HIV-positive patients. AB - BACKGROUND: In patients who are hepatitis B virus (HBV) DNA-positive, but HBV surface antigen (HBsAg) -negative, the infection is referred to as occult hepatitis B infection (OBI). Occult HBV infection is harmful when other liver diseases are present, and can aggravate liver damage in in patients with chronic liver diseases. In human immunodeficiency virus (HIV) infection the suppression of viral replication by the immune system might be inactivated, and classical HBV infection in OBI patients may occur. Health care professionals should be aware of OBI in HIV patients. The routine test for HBV infection in Iran is the enzyme linked immunosorbent assay for the HBV surface antigen (ELISA HBsAg); therefore, the aim of this study was to evaluate the prevalence of OBI in Iranian HIV patients. METHODS: This cross-sectional study was conducted in 2012 on sera from all the known and accessible HIV patients in Jahrom and Fassa, two cities in southern Iran. All samples were tested for the HBsAg, HBV core antibody (HBcAb). All the results were analyzed using SPSS. RESULTS: Of the 91 patients, seven (7.7%) were HBsAg-positive and forty-five (49.5%) were HBcAb-positive. In patients with negative HBsAg (84 patients), 39 (46.4%) were HBcAb positive and 53 (63%) were positive for HBV DNA. CONCLUSION: The prevalence of HBV infection is relatively high in HIV patients, and more accurate tests than those presently in use should be used for diagnosis. PMID- 26989736 TI - Hemolytic and cytotoxic properties of saponin purified from Holothuria leucospilota sea cucumber. AB - BACKGROUND: Holothuroids (sea cucumbers) are members of the phylum echinodermata, which produce saponins. Saponins exhibit a wide spectrum of pharmacological and biological activities. In this study, we isolated the crude saponins from the body wall of the dominant Iranian species of sea cucumber, Holothuria leucospilota (H. leucospilota). The purpose of this study was to confirm the presence of saponins in the Persian Gulf H. leucospilota and study the hemolytic and cytotoxic activities of these compounds. METHODS: The body wall of sea cucumber was dried and powdered and the crude saponins were isolated using various solvents. The crude saponins were further purified by column chromatography using HP-20 resin. The foam test, Thin Layer Chromatography (TLC), hemolytic assay, and Fourier Transform Infrared Spectroscopy (FTIR) confirmed the presence of saponins. Cytotoxicity was analyzed using a 3-(4, 5-dimethylthiazol-2 yl)-2, 5-diphenyltetrazolium bromide (MTT) assay on A549 cells, a human lung cancer cell line. RESULTS: The foam test, hemolytic assay, and TLC supported the presence of saponin compounds in the 80% ethanol fraction of H. leucospilota. The infrared (IR) spectrum of the extract showed hydroxyl (-OH), alkyl (C-H), ether (C-O) and ester (-C=O) absorption characteristic of teriterpenoid saponins. The C O-C absorption indicated glycoside linkages to the sapogenins. The crude saponin extracted from sea cucumber was cytotoxic to A549 cells. CONCLUSION: The 80% ethanol fraction of saponin isolated from H. leucospilota exhibited hemolytic activity and offers promise as an anti-cancer candidate. PMID- 26989737 TI - Determination of haptoglobin genotype in an Iranian population with idiopathic generalized epilepsy. AB - BACKGROUND: Haptoglobin (Hp) is a plasma alpha2-sialoglycoprotein that contains alpha and beta chains. It displays in three common phenotypes, Hp1-1, Hp2-1, and Hp2-2. Proteins expressed by polymorphic genes have grossly different molecular sizes resulting in different diffusion rates in the brain. Haptoglobin expressed by the Hp2-2 genotype has lower hemoglobin-binding capacity than Hp1-1 or Hp2-1 and is associated with idiopathic generalized epilepsy. METHODS: To determine polymorphism in haptoglobin genes in patients with idiopathic generalized tonic clonic seizures, 42 men, 42 women, and 50 controls were selected for this study. Genomic DNA was extracted from blood and studied by polymerase chain reactions (PCR). RESULTS: The amplified fragments for the Hp1-1 and Hp2-2 genotypes were 1757 and 3481 base pairs (bp) respectively, and the Hp2-1 genotype had both fragments, in addition to a 349-bp fragment. The distribution of the three major Hp phenotypes in epilepsy patients was 28.6 (1-1), 38.1 (2-1), and 33.3% (2-2) in the men, and 31 (1-1), 40.5 (2-1), and 28.6% (2-2) in the women. The distribution of Hp genotypes in controls was 22 (1-1), 40 (2-1), and 38% (2-2). CONCLUSION: We show that all Hp genotypes participate in idiopathic generalized epilepsy. PMID- 26989738 TI - Biochemical detection of N-Acyl homoserine lactone from biofilm-forming uropathogenic Escherichia coli isolated from urinary tract infection samples. AB - BACKGROUND: N-Acyl homoserine lactone (AHL) is found to be the main component of quorum sensing (QS) in Gram-negative bacteria and plays an important role in biofilm formation. Little information is available regarding the role of AHL in biofilm formation in Escherichia coli (E. coli). The purpose of this investigation was to biochemically detect and characterize AHL activity in biofilm-forming uropathogenic E. coli (UPEC) isolated from urine samples of the patients with urinary tract infections (UTIs) in Kerman, Iran. METHODS: Thirty five UPEC isolates were obtained from urine samples of the patients with UTIs referred to the Afzalipoor hospital. The isolates were identified by biochemical tests. Biofilm analyses of all the isolates were performed using the microtiter plate method at OD 490nm. N-Acyl homoserine lactone was separated from cell mass supernatants by liquid-liquid extraction (LLE) and analyzed by a colorimetric method. N-Acyl homoserine lactone functional groups were identified by Fourier Transform-Infrared Spectroscopy (FT-IR). RESULTS: The biofilm formation assay identified 10 (28.57%) isolates with strong, 16 (45.71%) with moderate, and 9 (25.71%) with weak biofilm activities. The UPEC isolates with strong and weak biofilm activities were subjected to AHL analyses. It was found that isolates with the highest AHL activities also exhibited strong adherence to microplate wells (P<=0.05). Two E. coli isolates with the highest AHL activities were selected for FT-IR spectroscopy. Peaks at 1764.33, 1377.99, and 1242.90 cm(-1) correspond to the C=O bond of the lactone ring, and the N=H and C-O bonds of the acyl chain, respectively. CONCLUSION: We found that many UPEC isolates exhibited strong biofilm formation. The control of this property by AHL may contribute to the pathogenesis of the organism in UTI's. PMID- 26989739 TI - Protective effects of Withania somnifera root on inflammatory markers and insulin resistance in fructose-fed rats. AB - BACKGROUND: We investigated the effects of Withania somnifera root (WS) on insulin resistance, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) in fructose-fed rats. METHODS: Forty-eight Wistar-Albino male rats were randomly divided into four groups (n=12); Group I as control, Group II as sham treated with WS by 62.5mg/g per diet, Group III fructose-fed rats received 10%W/V fructose, and Group IV fructose- and WS-fed rats. After eight weeks blood samples were collected to measure glucose, insulin, IL-6, and TNF-alpha levels in sera. RESULTS: Blood glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-R), IL-6, and TNF-alpha levels were all significantly greater in the fructose-fed rats than in the controls. Treatment with WS significantly (P < 0.05) inhibited the fructose-induced increases in glucose, insulin, HOMA-R, IL-6, and TNF-alpha. CONCLUSION: Our data suggest that WS normalizes hyperglycemia in fructose-fed rats by reducing inflammatory markers and improving insulin sensitivity. PMID- 26989740 TI - The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star. AB - BACKGROUND: Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. METHODS: The anti proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 ug/ml, and photographed by photo stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (p<0.05). RESULTS: Results illustrated that the brittle star extract exerted a dose- and time dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (p<0.05). CONCLUSION: These finding revealed the anti-angiogenic effects of brittle star methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies. PMID- 26989741 TI - Expression of TGF-beta3 in isolated fibroblasts from foreskin. AB - BACKGROUND: The multifunctional transforming growth factor beta (TGF-beta) is a glycoprotein that exists in three isoforms. TGF-beta3 expression increases in fetal wound healing and reduces fibronectin and collagen I and III deposition, and also improves the architecture of the neodermis which is a combination of blood vessels and connective tissue during wound healing. Fibroblasts are key cells in the wound healing process. TGF-beta3 plays a critical role in scar-free wound healing and fibroblast actions in the wound healing process. The aim of this study was to express the TGF-beta3 gene (tgf-b3) in human foreskin fibroblasts (HFF's). METHODS: We obtained HFF's from a newborn and a primary fibroblast culture was prepared. The cells were transfected with TGF-beta3-pCMV6 XL5 plasmid DNA by both lipofection and electroporation. Expression of TGF-beta3 was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The highest TGF-beta3 expression (8.3-fold greater than control) was obtained by lipofection after 72 hours using 3 ul of transfection reagent. Expression was 1.4-fold greater than control by electroporation. CONCLUSIONS: In this study, we successfully increased TGF-beta3 expression in primary fibroblast cells. In the future, grafting these transfected fibroblasts onto wounds can help the healing process without scarring. PMID- 26989742 TI - Transforming growth factor beta 1 869T/C and 915G/C polymorphisms and risk of autism spectrum disorders. AB - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) has been found to play a crucial role in early central nervous system development. Several studies have illustrated decreased TGF-beta1 levels in sera and brains of autistic children. Two point mutations in the TGF-beta1 signal peptide at 869T/C and 915G/C have been reported to influence TGF-beta1 expression. The aim of the present study was to investigate the correlation of TGF-beta1 polymorphisms and their haplotypes with autism. METHODS: This study was performed on 39 autistic patients and 35 age and sex-matched normal controls in an Iranian population, using the sequence specific primed-polymerase chain reaction (PCR-SSP) technique. Patients were divided into mild-to-moderate and severe groups according to the childhood autism rating scale. RESULTS: No significant differences were observed for allele, genotype, or haplotype frequencies between the autistics and controls. Only a slight difference was observed in GC25 between the controls and all children with autism. CONCLUSION: Thus, these results indicate that the polymorphisms in TGF beta1 gene may not play an important role in the development of autism. PMID- 26989743 TI - Pattern of infection and antibiotic activity among Streptococcus agalactiae isolates from adults in Mashhad, Iran. AB - BACKGROUND: One of the main causes of sexually transmitted diseases is group B beta- hemolytic streptococci (GBS) multiplying in the genital tracts. Penicillin is the most common drug for the treatment of infections caused by these bacteria, but in patients suffering from Penicillin allergy, Erythromycin and Clindamycin are used as alternative therapeutic drugs against GBS. Recently, resistance to these drugs has been reported more often. In this study, efforts have been made to determine the prevalence and antibiotic resistance of GBS. METHODS: Modified Christie Atkins Munch-Petersen (CAMP) test was conducted on over 2400 samples of urine and discharge taken from vagina, urethra and prostate. The drug sensitivity was performed by double disk sensitivity tests to Bacitracin, Trimethoprim, and Sulfamethoxazole and then the resistant samples were investigated by E-test to determine the minimal inhibitory concentrations (MICs) value. RESULTS: Twenty three vaginal and 10 urethral discharge, 27urine and 6 prostatic secretion samples were GBS positive. The most symbiotic microorganisms with GBS were strains of Enterococci (90%), Staphylococcus saprophyticus (25%) and Candida albicans (6%). The disk diffusion method showed 18 cases with Penicillin resistance (MIC: 1.5 mg/ml). CONCLUSION: Taken together, GBS carriers' rate in this study was found 20.65% (8.24% men and 12.4% women). Furthermore, findings showed high-level resistance to Erythromycin and Clindamycin. PMID- 26989744 TI - Toward the development of a single-round infection assay based on EGFP reporting for anti-HIV-1 drug discovery. AB - BACKGROUND: The rapid increase of HIV-1 strains resistant to current antiretroviral drugs is a challenge for successful AIDS therapy. This necessitates the development of novel drugs, and to this end, availability of screening systems for in vitro drug discovery is a priority. Herein, we report the modification of a previously developed system for increased sensitivity, ease of use, and cost-efficiency, based on the application of the EGFP marker. METHODS: A PCR-amplified gfp gene (gfp) was cloned into pmzNL4-3, the plasmid already designed to produce single-cycle replicable virions, in frame with the reverse-transcriptase gene to construct the pmzNL4-3/GFP plasmid. GFP-mzNL4-3 pseudo-typed virions, as the first progeny viruses, were recovered from the culture supernatant of HEK293T cells co-transfected with pmzNL4-3/GFP and the helper plasmids pSPAX2 and pMD2G, which respectively encode HIV-1 Gag-Pol and vesicular stomatitis virus glycoprotein. Single-cycle replication and virion production were assessed by syncytia formation, p24 antigen assays, and electron and fluorescence microscopy. RESULTS: The incorporation of EGFP into the viral particles allowed their quantification by fluorometry, flow-cytometry, and fluorescence microscopy; however, this modification did not affect the single round infectivity or production rate of the GFP fluorescence-emitting virions. CONCLUSIONS: Our results certify the development of a rapid, inexpensive, and safe GFP-reporting single-cycle replicable system for anti-HIV drug discovery. Further experiments are needed to measure the validity and robustness of the assay. PMID- 26989745 TI - Comparative Analysis of Peripheral Alkaline Phytase Protein Structures Expressed in E. coli. AB - BACKGROUND: Degradation of phytic acid to inorganic phosphate in domestic animals' diets requires thermostable phytase. Although Basillus subtilis phytase shows a potential to be degraded phytate complex in high temperature, the enzyme activities and yields need to be increased to make them possible for industrial application. METHODS: The phytase gene from Bacillus subtilis DR8886 was isolated from Dig Rostam hot mineral spring in Iran and cloned into pET21(+) and pET32(+). Expression was induced with 1.5 mM IPTG and the proteins were purified. RESULTS: The recombinant protein affected by thioredoxin (Trx) from pET32a-PhyC was estimated to constitute about 31% of the total soluble protein in the cells; its concentration was 3.5 ug/ml, and its maximal phytase activity was 15.9 U/ml, whereas the recombinant phytase from pET21a-PhyC was estimated to comprise about 19% of the total soluble protein; its concentration was 2.2 ug/ml, and its maximal phytase activity was 69 U/ml. The molecular masses of recombinant phytase with and without Trx were about 60 kDa and 42 kDa, respectively. Zymography confirmed that the recombinant enzymes were active. Although the concentration of the alkaline phytase expressed by pET32a was approximately 59% greater than that expressed by pET21, its phytase activity was approximately 77% less. CONCLUSION: This study showed that the peripheral gene (Trx) encoded by the pET32a (+) vector are the principal reason for the decrease in recombinant phytase enzyme activity. PMID- 26989746 TI - Refolding process of cysteine-rich proteins:Chitinase as a model. AB - BACKGROUND: Recombinant proteins overexpressed in E. coli are usually deposited in inclusion bodies. Cysteines in the protein contribute to this process. Inter- and intra- molecular disulfide bonds in chitinase, a cysteine-rich protein, cause aggregation when the recombinant protein is overexpressed in E. coli. Hence, aggregated proteins should be solubilized and allowed to refold to obtain native- or correctly- folded recombinant proteins. METHODS: Dilution method that allows refolding of recombinant proteins, especially at high protein concentrations, is to slowly add the soluble protein to refolding buffer. For this purpose: first, the inclusion bodies containing insoluble proteins were purified; second, the aggregated proteins were solubilized; finally, the soluble proteins were refolded using glutathione redox system, guanidinium chloride, dithiothreitol, sucrose, and glycerol, simultaneously. RESULTS: After protein solubilization and refolding, SDS-PAGE showed a 32 kDa band that was recognized by an anti-chitin antibody on western blots. CONCLUSIONS: By this method, cysteine-rich proteins from E. coli inclusion bodies can be solubilized and correctly folded into active proteins. PMID- 26989747 TI - Transcriptional analysis of VEGF-D and TGFbeta genes in MCF7 cells exposed to saponin isolated from Holothuria leucospilota (sea cucumber). AB - BACKGROUND: Marine natural products contain a wide range of bioactive compounds with therapeutic properties that have revealed crucial properties in the treatment of some diseases. Some of these compounds have recently received considerable attention for drug discovery. In this study we examined the anti angiogenic effect of saponin isolated from Holothuria leucospilota (sea cucumber) through evaluation of vascular endothelial growth factor D (VEGF-D) and transforming growth factor-beta (TGFbeta) expression in a breast cancer cell line. METHODS: To investigate the effect of SCS on VEGF-D and TGF-beta expression in breast cancer cells, the cells were treated with various concentrations of sample. After 48 h the viability of the cells was evaluated by trypan blue staining, and VEGF-D and TGFbeta mRNA expression was were evaluated by real time PCR. RESULTS: Our results revealed that SCS can suppress cell viability and VEGF D and TGFbeta mRNA expression in breast cancer cells. Sea cucumber saponin at a concentration of 12 MUg/ml inhibited VEGF-D and TGFbeta expression more than 90% compared with controls. CONCLUSION: Findings suggest that SCS could inhibit tumor growth via inhibition of angiogenesis. PMID- 26989748 TI - In silico analysis and molecular modeling of RNA polymerase, sigma S (RpoS) protein in Pseudomonas aeruginosa PAO1. AB - BACKGROUND: Sigma factors are proteins that regulate transcription in bacteria. Sigma factors can be activated in response to different environmental conditions. The rpoS (RNA polymerase, sigma S) gene encodes sigma-38 (sigma38, or RpoS), a 37.8 kDa protein in Pseudomonas aeruginosa (P. aeruginosa) strains. RpoS is a central regulator of the general stress response and operates in both retroactive and proactive manners; not only does it allow the cell to survive environmental challenges; it also prepares the cell for subsequent stresses (cross-protection). METHODS: The significance of RpoS for stress resistance and protein expression in stationary-phase P. aeruginosa cells was assessed. The goal of the current study was to characterize RpoS of P. aeruginosa PAO1 using bioinformatics tools. RESULTS: The results showed that RpoS is an unstable protein that belongs to the sigma-70 factor family. Secondary structure analysis predicted that random coil is the predominant structure followed by extended alpha helix. The three dimensional (3D) structure was modeled using SWISS-MODEL Workspace. CONCLUSION: Determination of sequence, function, structure, and predicted epitopes of RpoS is important for modeling of inhibitors that will help in the design of new drugs to combat multi-drug-resistant (MDR) strains. Such information may aid in the development of new diagnostic tools, drugs, and vaccines for treatment in endemic regions. PMID- 26989749 TI - Association of Htra1 gene polymorphisms with the risk of developing AMD in Iranian population. AB - BACKGROUND: Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD). This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high temperature requirement A-1 (HTRA1) gene polymorphisms with the risk of developing AMD in the Iranian population. METHODS: Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR) technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software. RESULTS: Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population. CONCLUSIONS: The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population. PMID- 26989750 TI - In silico analysis and modeling of ACP-MIP-PilQ chimeric antigen from Neisseria meningitidis serogroup B. AB - BACKGROUND: Neisseria meningitidis, a life-threatening human pathogen with the potential to cause large epidemics, can be isolated from the nasopharynx of 5-15% of adults. The aim of the current study was to evaluate biophysical and biochemical properties and immunological aspects of chimeric acyl-carrier protein macrophage infectivity potentiator protein-type IV pilus biogenesis protein antigen (ACP-MIP-PilQ) from N. meningitidis serogroup B strain. METHODS: Biochemical properties and multiple alignments were predicted by appropriate web servers. Secondary molecular structures were predicted based on Chou and Fasman, Garnier-Osguthorpe-Robson, and Neural Network methods. Tertiary modeling elucidated conformational properties of the chimeric protein. Proteasome cleavage and transporter associated with antigen processing (TAP) binding sites, and T- and B-cell antigenic epitopes, were predicted using bioinformatic web servers. RESULTS: Based on our in silico and immunoinformatics analyses, the ACP-MIP-PilQ protein (AMP) can induce high-level cross-strain bactericidal activity. In addition, several immune proteasomal cleavage sites were detected. The 22 epitopes associated with MHC class I and class II (DR) alleles were confirmed in the AMP. Thirty linear B-cell epitopes as antigenic regions were predicted from the full-length protein. CONCLUSION: All predicted properties of the AMP indicate it could be a good candidate for further immunological in vitro and in vivo studies. PMID- 26989751 TI - Gastroduodenal Perforation and Ulcer Associated With Rotavirus and Norovirus Infections in Japanese Children: A Case Report and Comprehensive Literature Review. AB - Background. There is no literature review on gastroduodenal perforation or ulcer (GDPU) with rotavirus (RV) and norovirus (NoV) gastroenteritis. Methods. Pediatric cases of GDPU or upper gastrointestinal bleeding with RV and NoV gastroenteritis were searched from September 1974 until October 2015 using PubMed, Google for English, other-language-publications, and Ichushi (http://www.jamas.or.jp) for Japanese-language publications. All reports confirming GDPU or upper gastrointestinal bleeding with RV and NoV gastroenteritis were eligible for inclusion in the study. In addition, clinical characteristics were reviewed. Results. A boy with duodenal ulcer (DU) and NoV gastroenteritis was described. There were 32 GDPU cases (23 RVs and 9 NoVs cases), including our case; with the exception of 1 case, all were Japanese. Mean age, male/female ratio, and symptoms' duration before admission were 21.6 months, 2.2, and 4.0 days, respectively. Vomiting was the most common symptom, followed by diarrhea, lethargy, fever, abdominal distension, and convulsion. Dehydration, hematemesis, melena, drowsiness or unconsciousness, shock, metabolic acidosis, leukocytosis, anemia, positive C-reactive protein, high blood urea nitrogen, and hyponatremia commonly occurred. Helicobacter pylori was a minor cause of GDPU. Duodenal (DP) or gastric perforation (GP) developed in 14 cases (10 DP/RVs, 1 GP/RV, and 3 DP/NoVs). Duodenal ulcer or gastric ulcer (GU) developed in 18 cases (10 DU/RVs, 4 DU/NoVs, 1 GU/RV, 1 GU + DU/NoV, and 2 upper gastrointestinal bleeding/RVs). The predominant perforation or ulcer site was in the duodenum. With the exception of 2 deaths from DU, all cases recovered. Conclusions. Race, young age, male, severe dehydration, metabolic acidosis, drowsiness and unconsciousness, and shock may be potential risk factors of GDPU associated with RV and NoV gastroenteritis. Limitation of this descriptive study warrants further investigations to determine the risk factors in these infections that could be associated with GDPU. PMID- 26989752 TI - High Frequency of Clinically Significant Bacteremia in Adults Hospitalized With Falciparum Malaria. AB - Background. African children with severe falciparum malaria commonly have concomitant Gram-negative bacteremia, but co-infection has been thought to be relatively rare in adult malaria. Methods. Adults with a diagnosis of falciparum malaria hospitalized at 4 tertiary referral hospitals in Myanmar had blood cultures collected at admission. The frequency of concomitant bacteremia and the clinical characteristics of the patients, with and without bacteremia, were explored. Results. Of 67 adults hospitalized with falciparum malaria, 9 (13% [95% confidence interval, 5.3%-21.6%]) were also bacteremic on admission, 7 (78%) with Gram-negative enteric organisms (Escherichia coli [n = 3], typhoidal Salmonella species [n = 3], nontyphoidal Salmonella [n = 1]). Bacteremic adults had more severe disease (median Respiratory Coma Acidosis Malaria [RCAM] score 3; interquartile range [IQR], 1-4) than those without bacteremia (median RCAM score 1; IQR, 1-2) and had a higher frequency of acute kidney injury (50% vs 16%, P = .03). Although 35 (52%) were at high risk of death (RCAM score >=2), all 67 patients in the study survived, 51 (76%) of whom received empirical antibiotics on admission. Conclusions. Bacteremia was relatively frequent in adults hospitalized with falciparum malaria in Myanmar. Like children in high transmission settings, bacteremic adults in this low transmission setting were sicker than nonbacteremic adults, and were often difficult to identify at presentation. Empirical antibiotics may also be appropriate in adults hospitalized with falciparum malaria in low transmission settings, until bacterial infection is excluded. PMID- 26989753 TI - Strongyloides stercoralis, Eosinophilia, and Type 2 Diabetes Mellitus: The Predictive Value of Eosinophilia in the Diagnosis of S stercoralis Infection in an Endemic Community. AB - Background. This study examines the predictive value of eosinophilia for Strongyloides stercoralis infection, as measured by enzyme-linked immunosorbent assay (ELISA) testing, in an endemic community. In remote communities, eosinophilia is frequently used as a proxy test for the presence of helminth infections. Past studies of eosinophilia and Strongyloides infection have been conducted in specific groups such as immigrants and refugees, or in subpopulations of nonendemic communities, rather than in endemic communities. Methods. We conducted a cross-sectional study of the relationship between eosinophilia and Strongyloides ELISA serology, as part of a study into the relationship between S stercoralis infection and type 2 diabetes mellitus (T2DM) in an Indigenous community in northern Australia. Results. Two hundred thirty nine adults had their eosinophil count and S stercoralis ELISA serology measured in 2012 and 2013, along with other biometric and metabolic data. Eosinophilia was found to have a relatively poor sensitivity (60.9%), specificity (71.1%), positive predictive value (54.6%), and negative predictive value (76.1%) for S stercoralis ELISA positivity in this group. However, there was a more constant relationship between eosinophilia and S Stercoralis ELISA positivity in patients with T2DM (negative predictive value 87.5%). Conclusion. This study suggests that the presence or absence of eosinophilia is not an adequate proxy test for S stercoralis infection in a community where the infection is prevalent, and that the association between eosinophilia and S stercoralis ELISA positivity is more constant in patients with T2DM. PMID- 26989754 TI - Bacterial Vaginosis and Pregnancy Outcome in Lagos, Nigeria. AB - Background. Bacterial vaginosis (BV) is a complex clinical syndrome characterized by alterations in the normal vaginal flora and a malodorous discharge when symptomatic. In pregnancy, BV has been associated with adverse outcomes such as miscarriage, premature rupture of membranes, preterm birth, and low birth weight. This study was conducted to determine the prevalence and associations of BV and pregnancy outcomes among pregnant women in Lagos University Teaching Hospital (LUTH). Methods. We conducted a prospective observational study with high vaginal swabs obtained from consecutive newly registered antenatal women between 14 and 36 weeks gestation. The women were monitored until delivery, and their pregnancy outcome and demographic data were obtained using an interviewer-administered questionnaire. Results. Bacterial vaginosis was diagnosed by Nugent score in 64 of 246 women, giving a prevalence rate of 26%. Bacterial vaginosis was significantly associated with preterm delivery (risk ratio [RR], 2.68; 95% confidence interval [CI], 1.44-4.98), low birth weight (RR, 3.20; 95% CI, 1.29-7.94), and premature rupture of membranes (RR, 6.75; 95% CI, 3.11-14.67). The association between BV and miscarriage (<28 weeks gestation) and neonatal admission for various morbidities was not statistically significant. Conclusions. The prevalence rate of BV among pregnant women in LUTH is high and is significantly associated with adverse pregnancy outcome. Routine screening and treatment of women preconceptually may enable interventions to prevent these adverse outcomes. PMID- 26989755 TI - START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection. AB - The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID- 26989756 TI - Commentary on the statistical properties of noise and its implication on general linear models in functional near-infrared spectroscopy. AB - Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging technique that uses low levels of light to measure changes in cerebral blood oxygenation levels. In the majority of NIRS functional brain studies, analysis of this data is based on a statistical comparison of hemodynamic levels between a baseline and task or between multiple task conditions by means of a linear regression model: the so-called general linear model. Although these methods are similar to their implementation in other fields, particularly for functional magnetic resonance imaging, the specific application of these methods in fNIRS research differs in several key ways related to the sources of noise and artifacts unique to fNIRS. In this brief communication, we discuss the application of linear regression models in fNIRS and the modifications needed to generalize these models in order to deal with structured (colored) noise due to systemic physiology and noise heteroscedasticity due to motion artifacts. The objective of this work is to present an overview of these noise properties in the context of the linear model as it applies to fNIRS data. This work is aimed at explaining these mathematical issues to the general fNIRS experimental researcher but is not intended to be a complete mathematical treatment of these concepts. PMID- 26989757 TI - False positives and false negatives in functional near-infrared spectroscopy: issues, challenges, and the way forward. AB - We highlight a significant problem that needs to be considered and addressed when performing functional near-infrared spectroscopy (fNIRS) studies, namely the possibility of inadvertently measuring fNIRS hemodynamic responses that are not due to neurovascular coupling. These can be misinterpreted as brain activity, i.e., "false positives" (errors caused by wrongly assigning a detected hemodynamic response to functional brain activity), or mask brain activity, i.e., "false negatives" (errors caused by wrongly assigning a not observed hemodynamic response in the presence of functional brain activity). Here, we summarize the possible physiological origins of these issues and suggest ways to avoid and remove them. PMID- 26989758 TI - Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis. AB - We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD. PMID- 26989759 TI - Bolus arrival time and its effect on tissue characterization with dynamic contrast-enhanced magnetic resonance imaging. AB - Matching the bolus arrival time (BAT) of the arterial input function (AIF) and tissue residue function (TRF) is necessary for accurate pharmacokinetic (PK) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We investigated the sensitivity of volume transfer constant ([Formula: see text]) and extravascular extracellular volume fraction ([Formula: see text]) to BAT and compared the results of four automatic BAT measurement methods in characterization of prostate and breast cancers. Variation in delay between AIF and TRF resulted in a monotonous change trend of [Formula: see text] and [Formula: see text] values. The results of automatic BAT estimators for clinical data were all comparable except for one BAT estimation method. Our results indicate that inaccuracies in BAT measurement can lead to variability among DCE MRI PK model parameters, diminish the quality of model fit, and produce fewer valid voxels in a region of interest. Although the selection of the BAT method did not affect the direction of change in the treatment assessment cohort, we suggest that BAT measurement methods must be used consistently in the course of longitudinal studies to control measurement variability. PMID- 26989760 TI - NOTCH3 is expressed in human apical papilla and in subpopulations of stem cells isolated from the tissue. AB - NOTCH plays a role in regulating stem cell function and fate decision. It is involved in tooth development and injury repair. Information regarding NOTCH expression in human dental root apical papilla (AP) and its residing stem cells (SCAP) is limited. Here we investigated the expression of NOTCH3, its ligand JAG1, and mesenchymal stem cell markers CD146 and STRO-1 in the AP or in the primary cultures of SCAP isolated from AP. Our in situ immunostaining showed that in the AP NOTCH3 and CD146 were co-expressed and associated with blood vessels having NOTCH3 located more peripherally. In cultured SCAP, NOTCH3 and JAG1 were co-expressed. Flow cytometry analysis showed that 7%, 16% and 98% of the isolated SCAP were positive for NOTCH3, STRO-1 and CD146, respectively with a rare 1.5% subpopulation of SCAP co-expressing all three markers. The expression level of NOTCH3 reduced when SCAP underwent osteogenic differentiation. Our findings are the first step towards defining the regulatory role of NOTCH3 in SCAP fate decision. PMID- 26989761 TI - Geographic distribution of insufficient sleep across the United States: a county level hotspot analysis. AB - INTRODUCTION: Insufficient sleep is associated with cardiometabolic risk and neurocognitive impairment. Determinants of insufficient sleep include many social and environmental factors. Assessment of geographic hot/coldspots may uncover novel risk groups and/or targets for public health intervention. The aim of this study was to discern geographic patterns in the first data set to include county level sleep data. METHODS: The 2009 Behavioral Risk Factor Surveillance System was used. Insufficient sleep was assessed with a survey item and dichotomized. Data from n = 2231 counties were available. Tests for significant spatial concentrations of high/low levels of insufficient sleep (hotspots/coldspots) used the Getis-Ord G* statistic of local spatial concentration, chosen due to the nature of missing data. RESULTS: Eighty-four counties were hotspots, with high levels of insufficient sleep (P < .01), and 45 were coldspots, with low insufficient sleep (P < .01). Hotspots were found in Alabama (1 county), Arkansas (1), Georgia (1), Illinois (1), Kentucky (25), Louisiana (1), Missouri (4), Ohio (7), Tennessee (12), Texas (9), Virginia (6), and West Virginia (16). Coldspots were found in Alabama (1 county), Georgia (2), Illinois (6), Iowa (6), Michigan (2), Minnesota (1), North Carolina (1), Texas (7), Virginia (12), and Wisconsin (6). Several contiguous hotspots and coldspots were evident. Notably, the 17 counties with the highest levels of insufficient sleep were found in a contiguous set at the intersection of Kentucky, Tennessee, Virginia, and West Virginia (all P < .0002). CONCLUSIONS: Geographic distribution of insufficient sleep in the United States is uneven. Some areas (most notably parts of Appalachia) experience disproportionately high amounts of insufficient sleep and may be targets of intervention. Further investigation of determinants of geographic variability needs to be explored, which would enhance the utility of these data for development of public health campaigns. PMID- 26989763 TI - Soft Computational Approaches for Prediction and Estimation of Software Development. PMID- 26989762 TI - Spontaneous Transethmoidal Meningoceles in Adults: Case Series with Emphasis on Surgical Management. AB - BACKGROUND: Spontaneous onset transethmoidal meningocele is a rare entity among the adult population. METHODS: A retrospective chart review was performed and cases of adults diagnosed with spontaneous transethmoidal meningoceles from November 2000 till February 2014 were reported. Data collected included demographics, clinical presentation, diagnostic modalities, and results. Intraoperative findings, the type of surgical reconstruction performed, and the percentage of recurrence, if present, were also reported. RESULTS: Ten cases of spontaneous transethmoidal meningoceles in adults were diagnosed. Eight were females and two males with a mean age of 47.5 years. All patients presented with CSF leakage with or without meningitis. They underwent a reconstruction of the base of skull defect using the temporalis fascia graft in addition to fibrin glue (Tissucol) and Surgicel (Ethicon). In two cases with a larger defect, a piece of septal bone and turbinate mucosa were applied achieving a watertight seal in all cases. CONCLUSION: Spontaneous transethmoidal meningocele in adults is a rare condition. It usually presents with clear rhinorrhea with or without meningitis and an endoscopic multilayer reconstruction is advocated for treatment of such conditions. PMID- 26989764 TI - Wear Behavior of Aluminium Metal Matrix Composite Prepared from Industrial Waste. AB - With an increase in the population and industrialization, a lot of valuable natural resources are depleted to prepare and manufacture products. However industrialization on the other hand has waste disposal issues, causing dust and environmental pollution. In this work, Aluminium Metal Matrix Composite is prepared by reinforcing 10 wt% and 20 wt% of wet grinder stone dust particles an industrial waste obtained during processing of quarry rocks which are available in nature. In the composite materials design wear is a very important criterion requiring consideration which ensures the materials reliability in applications where they come in contact with the environment and other surfaces. Dry sliding wear test was carried out using pin-on-disc apparatus on the prepared composites. The results reveal that increasing the reinforcement content from 10 wt% to 20 wt% increases the resistance to wear rate. PMID- 26989766 TI - Novel impact of EWI-2, CD9, and CD81 on TGF-beta signaling in melanoma. AB - Cell surface transmembrane protein IGFS8 (herein called EWI-2) negatively regulates melanoma TGF-beta signaling and is well positioned to control the transition in TGF-beta signaling from cytostatic (in early melanoma stages) to pro-invasion/metastasis (in later stages). EWI-2 functions by sequestering the tetraspanin proteins CD9 and CD81, thereby making them unavailable to support the association of TGFbeta receptor 1 with TGFbeta receptor 2. PMID- 26989765 TI - A Contribution of Beef to Human Health: A Review of the Role of the Animal Production Systems. AB - Meat and meat products constitute important source of protein, fat, and several functional compounds. Although beef consumption may implicate possible negative impacts on human health, its consumption can also contribute to human health. Quality traits of beef, as well as its nutritional properties, depend on animal genetics, feeding, livestock practices, and post mortem procedures. Available data show that emerging beef production systems are able to improve both, quality and nutritional traits of beef in a sustainable way. In this context, Argentina's actions are aimed at maximising beef beneficial effects and minimising its negative impact on human health, in a way of contributing to global food security. PMID- 26989767 TI - Slowing down the Grand Touring Prototype speed of cancer cells. AB - Enzymes involved in de novo production of guanosine triphosphate (GTP) have been recently revealed as integral components of melanoma progression through modulation of the activity of small GTPases. Here, we discuss the biology and therapeutic implications of these findings. PMID- 26989768 TI - The necessity for in vivo functional analysis in human medical genetics. AB - Approximately 50% of all congenital anomalies cannot be linked to any specific genetic etiology, but in recent years cost effective high throughput sequencing has emerged as an efficient strategy for identifying single nucleotide polymorphisms (SNPs) associated with disease. However, in many cases there is not enough evidence to determine if these SNPs underlie disease. To bridge this gap in our understanding advances in functional analyses are warranted. Several preclinical model systems are currently being utilized to provide such evidence, including the advantageous zebrafish embryo. While every system exhibits disadvantages and caveats, a new era of multidisciplinary research has evolved, which uses a broad spectrum of functional analysis tools. This approach will make it possible to identify potential therapeutic targets for both common and rare human disorders. PMID- 26989769 TI - Lost in transportation: Information measures and cognitive limits in multilayer navigation. AB - Cities and their transportation systems become increasingly complex and multimodal as they grow, and it is natural to wonder whether it is possible to quantitatively characterize our difficulty navigating in them and whether such navigation exceeds our cognitive limits. A transition between different search strategies for navigating in metropolitan maps has been observed for large, complex metropolitan networks. This evidence suggests the existence of a limit associated with cognitive overload and caused by a large amount of information that needs to be processed. In this light, we analyzed the world's 15 largest metropolitan networks and estimated the information limit for determining a trip in a transportation system to be on the order of 8 bits. Similar to the "Dunbar number," which represents a limit to the size of an individual's friendship circle, our cognitive limit suggests that maps should not consist of more than 250 connection points to be easily readable. We also show that including connections with other transportation modes dramatically increases the information needed to navigate in multilayer transportation networks. In large cities such as New York, Paris, and Tokyo, more than 80% of the trips are above the 8-bit limit. Multimodal transportation systems in large cities have thus already exceeded human cognitive limits and, consequently, the traditional view of navigation in cities has to be revised substantially. PMID- 26989770 TI - How many cents on the dollar? Women and men in product markets. AB - Gender inequality in contemporary U.S. society is a well-documented, widespread phenomenon. However, little is known about gender disparities in product markets. This study is the first to use actual market data to study the behavior of women and men as sellers and buyers and differences in market outcomes. We analyze a unique and large data set containing all eBay auction transactions of most popular products by private sellers between the years 2009 and 2012. Women sellers received a smaller number of bids and lower final prices than did equally qualified men sellers of the exact same product. On average, women sellers received about 80 cents for every dollar a man received when selling the identical new product and 97 cents when selling the same used product. These findings held even after controlling for the sentiments that appear in the text of the sellers' listings. Nonetheless, it is worth noting that this gap varied by the type of the product being sold. As a policy, eBay does not reveal the gender of users. We attribute the price differences to the ability of buyers to discern the gender of the seller. We present results from an experiment that shows that people accurately identify the gender of sellers on the basis of typical information provided in postings. We supplement the analysis with an additional off-eBay experiment showing that, in a controlled setting, people are willing to pay less for money-value gift cards when they are sold by women rather than men. PMID- 26989771 TI - Dynamically variable negative stiffness structures. AB - Variable stiffness structures that enable a wide range of efficient load-bearing and dexterous activity are ubiquitous in mammalian musculoskeletal systems but are rare in engineered systems because of their complexity, power, and cost. We present a new negative stiffness-based load-bearing structure with dynamically tunable stiffness. Negative stiffness, traditionally used to achieve novel response from passive structures, is a powerful tool to achieve dynamic stiffness changes when configured with an active component. Using relatively simple hardware and low-power, low-frequency actuation, we show an assembly capable of fast (<10 ms) and useful (>100*) dynamic stiffness control. This approach mitigates limitations of conventional tunable stiffness structures that exhibit either small (<30%) stiffness change, high friction, poor load/torque transmission at low stiffness, or high power active control at the frequencies of interest. We experimentally demonstrate actively tunable vibration isolation and stiffness tuning independent of supported loads, enhancing applications such as humanoid robotic limbs and lightweight adaptive vibration isolators. PMID- 26989772 TI - Circumstellar disks of the most vigorously accreting young stars. AB - Stars may not accumulate their mass steadily, as was previously thought, but in a series of violent events manifesting themselves as sharp stellar brightening. These events can be caused by fragmentation due to gravitational instabilities in massive gaseous disks surrounding young stars, followed by migration of dense gaseous clumps onto the star. Our high-resolution near-infrared imaging has verified the presence of the key associated features, large-scale arms and arcs surrounding four young stellar objects undergoing luminous outbursts. Our hydrodynamics simulations and radiative transfer models show that these observed structures can indeed be explained by strong gravitational instabilities occurring at the beginning of the disk formation phase. The effect of those tempestuous episodes of disk evolution on star and planet formation remains to be understood. PMID- 26989774 TI - Toughness of carbon nanotubes conforms to classic fracture mechanics. AB - Defects in crystalline structure are commonly believed to degrade the ideal strength of carbon nanotubes. However, the fracture mechanisms induced by such defects, as well as the validity of solid mechanics theories at the nanoscale, are still under debate. We show that the fracture toughness of single-walled nanotubes (SWNTs) conforms to the classic theory of fracture mechanics, even for the smallest possible vacancy defect (~2 A). By simulating tension of SWNTs containing common types of defects, we demonstrate how stress concentration at the defect boundary leads to brittle (unstable) fracturing at a relatively low strain, degrading the ideal strength of SWNTs by up to 60%. We find that, owing to the SWNT's truss-like structure, defects at this scale are not sharp and stress concentrations are finite and low. Moreover, stress concentration, a geometric property at the macroscale, is interrelated with the SWNT fracture toughness, a material property. The resulting SWNT fracture toughness is 2.7 MPa m(0.5), typical of moderately brittle materials and applicable also to graphene. PMID- 26989773 TI - Reorganization of chromosome architecture in replicative cellular senescence. AB - Replicative cellular senescence is a fundamental biological process characterized by an irreversible arrest of proliferation. Senescent cells accumulate a variety of epigenetic changes, but the three-dimensional (3D) organization of their chromatin is not known. We applied a combination of whole-genome chromosome conformation capture (Hi-C), fluorescence in situ hybridization, and in silico modeling methods to characterize the 3D architecture of interphase chromosomes in proliferating, quiescent, and senescent cells. Although the overall organization of the chromatin into active (A) and repressive (B) compartments and topologically associated domains (TADs) is conserved between the three conditions, a subset of TADs switches between compartments. On a global level, the Hi-C interaction matrices of senescent cells are characterized by a relative loss of long-range and gain of short-range interactions within chromosomes. Direct measurements of distances between genetic loci, chromosome volumes, and chromatin accessibility suggest that the Hi-C interaction changes are caused by a significant reduction of the volumes occupied by individual chromosome arms. In contrast, centromeres oppose this overall compaction trend and increase in volume. The structural model arising from our study provides a unique high resolution view of the complex chromosomal architecture in senescent cells. PMID- 26989775 TI - The pace of plant community change is accelerating in remnant prairies. AB - Patterns of biodiversity are changing rapidly. "Legacy studies" use historical data to document changes between past and present communities, revealing long term trends that can often be linked to particular drivers of ecological change. However, a single pair of historical samples cannot ascertain whether rates of change are consistent or whether the impact and identity of drivers have shifted. Using data from a second resurvey of 47 Wisconsin prairie remnants, we show that the pace of community change has increased with shifts in the strength of particular drivers. Annual rates of local colonization and extinction accelerated by 129 and 214%, respectively, between 1950 and 1987 and between 1987 and 2012. Two anthropogenic drivers-patch area and fire history-increased in importance between these periods. As the strength and number of anthropogenic forces increase, rates of biodiversity change are likely to accelerate in other ecosystems as well. PMID- 26989776 TI - Ocean acidification causes structural deformities in juvenile coral skeletons. AB - Rising atmospheric CO2 is causing the oceans to both warm and acidify, which could reduce the calcification rates of corals globally. Successful coral recruitment and high rates of juvenile calcification are critical to the replenishment and ultimate viability of coral reef ecosystems. Although elevated Pco2 (partial pressure of CO2) has been shown to reduce the skeletal weight of coral recruits, the structural changes caused by acidification during initial skeletal deposition are unknown. We show, using high-resolution three-dimensional x-ray microscopy, that ocean acidification (Pco2 ~900 MUatm, pH ~7.7) not only causes reduced overall mineral deposition but also a deformed and porous skeletal structure in newly settled coral recruits. In contrast, elevated temperature (+3 degrees C) had little effect on skeletal formation except to partially mitigate the effects of elevated Pco2. The striking structural deformities we observed show that new recruits are at significant risk, being unable to effectively build their skeletons in the Pco2 conditions predicted to occur for open ocean surface waters under a "business-as-usual" emissions scenario [RCP (representative concentration pathway) 8.5] by the year 2100. PMID- 26989777 TI - Asymmetric excitation of surface plasmons by dark mode coupling. AB - Control over surface plasmons (SPs) is essential in a variety of cutting-edge applications, such as highly integrated photonic signal processing systems, deep subwavelength lasing, high-resolution imaging, and ultrasensitive biomedical detection. Recently, asymmetric excitation of SPs has attracted enormous interest. In free space, the analog of electromagnetically induced transparency (EIT) in metamaterials has been widely investigated to uniquely manipulate the electromagnetic waves. In the near field, we show that the dark mode coupling mechanism of the classical EIT effect enables an exotic and straightforward excitation of SPs in a metasurface system. This leads to not only resonant excitation of asymmetric SPs but also controllable exotic SP focusing by the use of the Huygens-Fresnel principle. Our experimental findings manifest the potential of developing plasmonic metadevices with unique functionalities. PMID- 26989778 TI - Nanoscale rotary apparatus formed from tight-fitting 3D DNA components. AB - We report a nanoscale rotary mechanism that reproduces some of the dynamic properties of biological rotary motors in the absence of an energy source, such as random walks on a circle with dwells at docking sites. Our mechanism is built modularly from tight-fitting components that were self-assembled using multilayer DNA origami. The apparatus has greater structural complexity than previous mechanically interlocked objects and features a well-defined angular degree of freedom without restricting the range of rotation. We studied the dynamics of our mechanism using single-particle experiments analogous to those performed previously with actin-labeled adenosine triphosphate synthases. In our mechanism, rotor mobility, the number of docking sites, and the dwell times at these sites may be controlled through rational design. Our prototype thus realizes a working platform toward creating synthetic nanoscale rotary motors. Our methods will support creating other complex nanoscale mechanisms based on tightly fitting, sterically constrained, but mobile, DNA components. PMID- 26989779 TI - Dramatic performance of Clostridium thermocellum explained by its wide range of cellulase modalities. AB - Clostridium thermocellum is the most efficient microorganism for solubilizing lignocellulosic biomass known to date. Its high cellulose digestion capability is attributed to efficient cellulases consisting of both a free-enzyme system and a tethered cellulosomal system wherein carbohydrate active enzymes (CAZymes) are organized by primary and secondary scaffoldin proteins to generate large protein complexes attached to the bacterial cell wall. This study demonstrates that C. thermocellum also uses a type of cellulosomal system not bound to the bacterial cell wall, called the "cell-free" cellulosomal system. The cell-free cellulosome complex can be seen as a "long range cellulosome" because it can diffuse away from the cell and degrade polysaccharide substrates remotely from the bacterial cell. The contribution of these two types of cellulosomal systems in C. thermocellum was elucidated by characterization of mutants with different combinations of scaffoldin gene deletions. The primary scaffoldin, CipA, was found to play the most important role in cellulose degradation by C. thermocellum, whereas the secondary scaffoldins have less important roles. Additionally, the distinct and efficient mode of action of the C. thermocellum exoproteome, wherein the cellulosomes splay or divide biomass particles, changes when either the primary or secondary scaffolds are removed, showing that the intact wild-type cellulosomal system is necessary for this essential mode of action. This new transcriptional and proteomic evidence shows that a functional primary scaffoldin plays a more important role compared to secondary scaffoldins in the proper regulation of CAZyme genes, cellodextrin transport, and other cellular functions. PMID- 26989781 TI - Anderson localization of electrons in single crystals: Li (x) Fe(7)Se(8). AB - Anderson (disorder-induced) localization, proposed more than half a century ago, has inspired numerous efforts to explore the absence of wave diffusions in disordered media. However, the proposed disorder-induced metal-insulator transition (MIT), associated with the nonpropagative electron waves, has hardly been observed in three-dimensional (3D) crystalline materials, let alone single crystals. We report the observation of an MIT in centimeter-size single crystals of Li x Fe7Se8 induced by lattice disorder. Both specific heat and infrared reflectance measurements reveal the presence of considerable electronic states in the vicinity of the Fermi level when the MIT occurs, suggesting that the transition is not due to Coulomb repulsion mechanism. The 3D variable range hopping regime evidenced by electrical transport measurements at low temperatures indicates the localized nature of the electronic states on the Fermi level. Quantitative analyses of carrier concentration, carrier mobility, and simulated density of states (DOS) fully support that Li x Fe7Se8 is an Anderson insulator. On the basis of these results, we provide a unified DOS picture to explain all the experimental results, and a schematic diagram for finding other potential Anderson insulators. This material will thus serve as a rich playground for both theoretical and experimental investigations on MITs and disorder-induced phenomena. PMID- 26989780 TI - Citrullination-acetylation interplay guides E2F-1 activity during the inflammatory response. AB - Peptidyl arginine deiminase 4 (PAD4) is a nuclear enzyme that converts arginine residues to citrulline. Although increasingly implicated in inflammatory disease and cancer, the mechanism of action of PAD4 and its functionally relevant pathways remains unclear. E2F transcription factors are a family of master regulators that coordinate gene expression during cellular proliferation and diverse cell fates. We show that E2F-1 is citrullinated by PAD4 in inflammatory cells. Citrullination of E2F-1 assists its chromatin association, specifically to cytokine genes in granulocyte cells. Mechanistically, citrullination augments binding of the BET (bromodomain and extra-terminal domain) family bromodomain reader BRD4 (bromodomain-containing protein 4) to an acetylated domain in E2F-1, and PAD4 and BRD4 coexist with E2F-1 on cytokine gene promoters. Accordingly, the combined inhibition of PAD4 and BRD4 disrupts the chromatin-bound complex and suppresses cytokine gene expression. In the murine collagen-induced arthritis model, chromatin-bound E2F-1 in inflammatory cells and consequent cytokine expression are diminished upon small-molecule inhibition of PAD4 and BRD4, and the combined treatment is clinically efficacious in preventing disease progression. Our results shed light on a new transcription-based mechanism that mediates the inflammatory effect of PAD4 and establish the interplay between citrullination and acetylation in the control of E2F-1 as a regulatory interface for driving inflammatory gene expression. PMID- 26989782 TI - Tomographic reconstruction of circularly polarized high-harmonic fields: 3D attosecond metrology. AB - Bright, circularly polarized, extreme ultraviolet (EUV) and soft x-ray high harmonic beams can now be produced using counter-rotating circularly polarized driving laser fields. Although the resulting circularly polarized harmonics consist of relatively simple pairs of peaks in the spectral domain, in the time domain, the field is predicted to emerge as a complex series of rotating linearly polarized bursts, varying rapidly in amplitude, frequency, and polarization. We extend attosecond metrology techniques to circularly polarized light by simultaneously irradiating a copper surface with circularly polarized high harmonic and linearly polarized infrared laser fields. The resulting temporal modulation of the photoelectron spectra carries essential phase information about the EUV field. Utilizing the polarization selectivity of the solid surface and by rotating the circularly polarized EUV field in space, we fully retrieve the amplitude and phase of the circularly polarized harmonics, allowing us to reconstruct one of the most complex coherent light fields produced to date. PMID- 26989784 TI - Experimental nonlocal and surreal Bohmian trajectories. AB - Weak measurement allows one to empirically determine a set of average trajectories for an ensemble of quantum particles. However, when two particles are entangled, the trajectories of the first particle can depend nonlocally on the position of the second particle. Moreover, the theory describing these trajectories, called Bohmian mechanics, predicts trajectories that were at first deemed "surreal" when the second particle is used to probe the position of the first particle. We entangle two photons and determine a set of Bohmian trajectories for one of them using weak measurements and postselection. We show that the trajectories seem surreal only if one ignores their manifest nonlocality. PMID- 26989785 TI - Hidden in plain sight: Cryptic and endemic malaria parasites in North American white-tailed deer (Odocoileus virginianus). AB - Malaria parasites of the genus Plasmodium are diverse in mammal hosts, infecting five mammalian orders in the Old World, but were long considered absent from the diverse deer family (Cervidae) and from New World mammals. There was a description of a Plasmodium parasite infecting a single splenectomized white tailed deer (WTD; Odocoileus virginianus) in 1967 but none have been reported since, which has proven a challenge to our understanding of malaria parasite biogeography. Using both microscopy and polymerase chain reaction, we screened a large sample of native and captive ungulate species from across the United States for malaria parasites. We found a surprisingly high prevalence (up to 25%) and extremely low parasitemia of Plasmodium parasites in WTD throughout the eastern United States. We did not detect infections in the other ungulate species nor in western WTD. We also isolated the parasites from the mosquito Anopheles punctipennis. Morphologically, the parasites resemble the parasite described in 1967, Plasmodium odocoilei. Our analysis of the cytochrome b gene revealed two divergent Plasmodium clades in WTD representative of species that likely diverged 2.3 to 6 million years ago, concurrent with the arrival of the WTD ancestor into North America across Beringia. Multigene phylogenetic analysis placed these clades within the larger malaria parasite clade. We document Plasmodium parasites to be common in WTD, endemic to the New World, and as the only known malaria parasites from deer (Cervidae). These findings reshape our knowledge of the phylogeography of the malaria parasites and suggest that other mammal taxa may harbor infection by endemic and occult malaria parasites. PMID- 26989783 TI - Reconsidering plant memory: Intersections between stress recovery, RNA turnover, and epigenetics. AB - Plants grow in dynamic environments where they can be exposed to a multitude of stressful factors, all of which affect their development, yield, and, ultimately, reproductive success. Plants are adept at rapidly acclimating to stressful conditions and are able to further fortify their defenses by retaining memories of stress to enable stronger or more rapid responses should an environmental perturbation recur. Indeed, one mechanism that is often evoked regarding environmental memories is epigenetics. Yet, there are relatively few examples of such memories; neither is there a clear understanding of their duration, considering the plethora of stresses in nature. We propose that this field would benefit from investigations into the processes and mechanisms enabling recovery from stress. An understanding of stress recovery could provide fresh insights into when, how, and why environmental memories are created and regulated. Stress memories may be maladaptive, hindering recovery and affecting development and potential yield. In some circumstances, it may be advantageous for plants to learn to forget. Accordingly, the recovery process entails a balancing act between resetting and memory formation. During recovery, RNA metabolism, posttranscriptional gene silencing, and RNA-directed DNA methylation have the potential to play key roles in resetting the epigenome and transcriptome and in altering memory. Exploration of this emerging area of research is becoming ever more tractable with advances in genomics, phenomics, and high-throughput sequencing methodology that will enable unprecedented profiling of high resolution stress recovery time series experiments and sampling of large natural populations. PMID- 26989786 TI - Impact of Ethanol and Saccharin on Fecal Microbiome in Pregnant and Non-Pregnant Mice. AB - Research identifying connections between the gastrointestinal flora and human health has developed at a rapid pace. Several studies link the gut microbiome to a variety of biological functions beyond the gastrointestinal tract. Changes in our diets, including the consumption of artificial sweeteners, have profound effects on the composition of the gut microbiome and can, in turn, affect brain function, glucose tolerance, and inflammation. Sweeteners are often used to encourage consumption of agents such as ethanol and nicotine in laboratory studies using rodents. Studies aiming to examine the effects of agents like ethanol on the developing nervous system administer these agents during pregnancy. To date, there have been no studies exploring the impact of the combination of dietary ethanol and saccharin during pregnancy on the gut microbiome in either humans or laboratory animal models. In the study presented, we evaluated the impact of ethanol in either water or saccharin on the fecal microbiome in pregnant and non-pregnant mice using a qPCR approach. We found that the combination of ethanol and saccharin produced different effects than ethanol in water, depending on pregnancy status. Levels of Clostridium were reduced in ethanol-saccharin but not ethanol-water drinking mice, even though the total levels of ethanol consumed were the same for the two groups. Eubacteria were increased in the pregnant, but decreased in the non-pregnant, ethanol-saccharin drinking group. These treatment and pregnancy specific changes could impact the development of the offspring. In developing and quality checking our primer sets for these studies we identified several problems within previous research in the field. The technical drawbacks in previous studies, as well as our own study, are discussed. Despite some progress in the ability to study the gut microbiome, more advances and standardization of practices should be established to improve the reliability and validity of microbiome research. PMID- 26989788 TI - Calculation of the Per Hypothesis Error Rate via Sums of Steck's Determinants. AB - In this note we provide a straightforward approach for calculation of the per hypothesis error rate in a multiple testing framework given a general stepwise testing procedure. This approach is based on a general result due to coined Steck's determinant. This result allows for a direct comparison across various testing procedures and illustrates some common misperceptions regarding the optimality of each method. PMID- 26989787 TI - Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use. AB - Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use "real world" printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 (Rantes), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects. PMID- 26989789 TI - Career planning: Question time. PMID- 26989790 TI - Biotechnology industrialization is the result of basic life science. PMID- 26989791 TI - [Nitrous oxide in dentistry]. PMID- 26989793 TI - Neuroimaging in neuropsychiatric disorders. PMID- 26989794 TI - Do psychotherapies produce neurobiological effects? AB - BACKGROUND: An area of recent interest in psychiatric research is the application of neuroimaging techniques to investigate neural events associated with the development and the treatment of symptoms in a number of psychiatric disorders. OBJECTIVE: To examine whether psychological therapies modulate brain activity and, if so, to examine whether these changes similar to those found with relevant pharmacotherapy in various mental disorders. METHODS: Relevant data were identified from Pubmed and PsycInfo searches up to July 2005 using combinations of keywords including 'psychological therapy', 'behaviour therapy', 'depression', 'panic disorder', 'phobia', 'obsessive compulsive disorder', 'schizophrenia', 'psychosis', 'brain activity', 'brain metabolism', 'PET', 'SPECT' and 'fMRI'. RESULTS: There was ample evidence to demonstrate that psychological therapies produce changes at the neural level. The data, for example in depression, panic disorder, phobia and obsessive compulsive disorder (OCD), clearly suggested that a change in patients' symptoms and maladaptive behaviour at the mind level with psychological techniques is accompanied with functional brain changes in relevant brain circuits. In many studies, cognitive therapies and drug therapies achieved therapeutic gains through the same neural pathways although the two forms of treatment may still have different mechanisms of action. CONCLUSIONS: Empirical research indicates a close association between the 'mind' and the 'brain' in showing that changes made at the mind level in a psychotherapeutic context produce changes at the brain level. The investigation of changes in neural activity with psychological therapies is a novel area which is likely to enhance our understanding of the mechanisms for therapeutic changes across a range of disorders. PMID- 26989795 TI - Imaging auditory hallucinations in schizophrenia. AB - It is increasingly recognized that there are a heterogeneous range of symptoms within the syndrome of schizophrenia and that some of these also occur frequently within other psychiatric conditions. An approach similar to that in neuropsychology, where cases are grouped based on a discrete deficit, or in this case a discrete symptom, rather than a cause or diagnosis, may be useful in exploring the neural correlates of psychotic symptomatology. Functional neuroimaging provides an excellent tool for investigating the in vivo cortical function of patients with schizophrenia. Auditory verbal hallucinations are one of the most commonly occurring psychotic symptoms in schizophrenia; and this paper examines the progress that has been made in utilizing neuroimaging techniques to investigate auditory hallucinations in schizophrenia and review potential implications for treatment and future directions for research. PMID- 26989796 TI - Depression and pain: an overview. AB - BACKGROUND: Depression and pain are both burdensome ailments that affect a major proportion of the population. It is evident that depression and pain frequently coexist, with treatment and outcome implications. OBJECTIVE: To review the literature on the nature, prevalence and co-morbidity of depression and pain, the biological and psychological mechanisms involved and treatment options, thus presenting a broad overview of the current information available. METHODS: Relevant sources were identified from PubMed and Medline databases using a combination of keywords including depression, pain, prevalence, co-morbidity, biological and psychological mechanisms, serotonin (5-HT), norepinephrine (NE), hypothalamic-pituitary-adrenal (HPA) axis, amygdala, functional magnetic resonance imaging (fMRI), antidepressant and psychological therapy. RESULTS: It is evident from the research that depression and pain are common co-morbidities. Pain as a physical symptom of depression affects approximately 65% of patients, leading to less favourable outcomes and greater health care utilization. Moreover, depression is a common feature in chronic pain patients and can affect pain threshold and tolerance. Evidence from biological and psychological studies has revealed mechanisms that link chronic pain to depression. Several classes of anti-depressants and psychological interventions have been used successfully in the treatment of somatic symptoms of depression and for a variety of pain syndromes. CONCLUSIONS: Pain and depression are linked by overlapping phenomenology, neurobiology and therapy. They are mutually interacting, and the interaction has significant treatment and outcome implications. PMID- 26989797 TI - Functional neuroimaging studies in mood disorders. AB - BACKGROUND: Our understanding of the neural circuitry involved in mood disorders is rapidly expanding through the ever-increasing application of functional brain imaging techniques. OBJECTIVES: A selective review of functional neuroimaging studies in patients with primary mood disorders was undertaken in order to identify points of commonality and controversy in the existing literature. METHODS: Articles published between 1980 and July 2005 were identified using a range of keywords from relevant on-line databases and key journals. RESULTS: Increased activity within limbic regions has been consistently associated with depressive states and may also be present in manic states too. Dorsal and ventral prefrontal regions appear compromised as suggested by emerging evidence of cortical inefficiency within prefrontal regions or reductions in their connectivity with limbic areas. Most of the functional changes observed are at least partly reversible following clinical remission although deficits in prefrontal regions may be state-related. CONCLUSIONS: Despite the use of disparate functional imaging modalities, there is a convergence of findings, and the results described do not appear to differ between unipolar and bipolar depression. However, further data are required in order to fully determine the functional changes occurring during manic states. Future work will also need to elucidate the effects of medication, the utility of specific cognitive tasks, and blood oxygenation level-dependent interactions within these affective states. PMID- 26989798 TI - Cerebrovascular autoregulation as a neuroimaging tool. AB - Functional transcranial Doppler (fTCD) sonography provides a high temporal resolution measure of blood flow and has over the years proved to be a valuable tool in the clinical evaluation of patients with cerebrovascular disorders. More recently, due to advances in physics and computing, it has become possible to derive indices of cerebrovascular autoregulation (CA) as well as cerebrovascular pressure reactivity (CR), using non-invasive techniques. These indices provide a dynamic representation of the brain's regulatory blood flow mechanisms not only in pathological states but also in health. However, whilst the temporal resolution of these regulatory indices is very good, spatially, the localization of brain regions remains very poor, thus limiting its brain mapping capacity. Functional MRI, on the contrary, is a brain-imaging technique that operates on similar blood flow principles; however, unlike fTCD, it provides high spatial resolution. Because both fTCD and fMRI determine blood flow-dependant imaging parameters, the coupling of fTCD with fMRI may provide greater insight into brain function by virtue of the combined enhanced temporal and spatial resolution that each technique affords. This review summarizes the fTCD technique with particular emphasis on the CA and CR indices and their relationship in traumatic brain injury as well as in health. PMID- 26989799 TI - Differential BOLD responses to auditory target stimuli associated with a skin conductance response. AB - BACKGROUND: The orienting reflex (OR) is a fundamental biological mechanism thought to reflect automatic adaptive processing of environmental stimuli necessary for successful interaction with the environment. It has been hypothesized that the OR is generated in response to novelty such as in the case where a mismatch results between an internal neuronal template stored in working memory and incoming stimuli. Recent blood oxygenated level dependant (BOLD) activation studies that have investigated networks involved in the processing of novelty have suggested the recruitment of a distributed limbic-neocortical network. In the present study, event-related functional resonance imaging with simultaneous autonomic electrodermal activity was used to detect single trials of an auditory oddball task associated with the OR. RESULTS: The pattern of activations indicated two distinct, but partially overlapping, networks. Predominantly, frontal activations were seen for the target stimuli that did elicit an OR, including the orbitofrontal gyrus and anterior cingulate gyrus, as well as activations in the anterior thalamus and cerebellum. On contrary, parietal activations including the supramarginal gyrus and precuneus were seen for the target stimuli that that did not elicit an OR. PMID- 26989800 TI - Putting the brain in Jeopardy: a novel comprehensive and expressive language task? AB - OBJECTIVE: To develop and test a novel fMRI compatible comprehensive and expressive language task that reliably and predictably activates both Wernicke's and Broca's cortical brain regions, respectively, and has utility for the determination of hemispheric language dominance. METHODS: Ten healthy men (seven) and women (three) were administered a task based on the television game Jeopardy that was adapted for fMRI presentation. The task was programmed using E-PRIME software and designed to run as an event-related experiment. The study was conducted on 3 T MRI Phillips Intera scanner, and data was anlysed using Brain Voyager QX. All subjects provided written informed consent. RESULTS: The Jeopardy task produced robust left hemisphere activation in regions corresponding to Wernicke's and Broca's areas. CONCLUSION: This novel fMRI compatible task (Jeopardy) reliably maps both Broca's and Wernicke's areas with robust hemispheric lateralization. It is potentially useful in language localization studies as it offers advantages over conventional procedures and other fMRI tasks by virtue of being non-invasive and mapping both language areas in one experiment. PMID- 26989801 TI - Magnetic resonance spectroscopic measurement of cerebral gamma-aminobutyric acid concentrations in patients with bipolar disorders. AB - BACKGROUND: Animal models of depression and psychopharmacological mechanisms of action suggest the importance of the gamma-amino butyric acid (GABA) system in the pathophysiology of mood disorders. Mood stabilizers have overlapping effects on GABAergic neurotransmission, and antidepressant use has been associated with alterations in GABAB receptor function. Magnetic resonance spectroscopy (MRS) provides an opportunity to noninvasively assess cerebral GABA concentrations in anterior paralimbic circuits that have been implicated in mood disorders. METHODS: In bipolar disorder patients and healthy control subjects, we used MRS with a modified GABA-edited point resolved spectroscopy sequence (TE 68 ms, TR 1500 ms, 512 averages, total scan time 26 min) to assess GABA in an 18-cm3 occipital voxel. In addition, in another cohort of bipolar disorder patients and healthy control subjects, we similarly assessed GABA in a 12.5-cm3 medial prefrontal/anterior cingulate (MPF/AC) voxel. The concentration of GABA was referenced to creatine (Cr) from unedited spectra. RESULTS: In bipolar patients and controls, we consistently detected 3.0 p.p.m. GABA peaks in occipital lobe and MPF/AC. In 16 bipolar (nine bipolar I and seven bipolar II) disorder patients, compared with six healthy control subjects, mean occipital GABA/Cr concentration was 61% higher. In addition, in 15 bipolar (five bipolar I, nine bipolar II, and one bipolar not otherwise specified) disorder patients, compared with six healthy control subjects, mean MPF/AC GABA/Cr concentration tended to be 41% higher. CONCLUSIONS: Patients with bipolar disorders may have increased cerebral GABA concentrations. Although this was more evident in the occipital lobe, MPC/AC GABA disturbance may be of greater potential interest in view the more established role of MPF/AC in affective processing. Additional studies are warranted to assess changes in GABAergic neurotransmission and the influences of diagnosis, mood state, and medication status in bipolar disorder patients. PMID- 26989802 TI - Ovarian parameters and ovarian blood flow of women living in the area of environmental crisis. AB - BACKGROUND AND OBJECTIVES: Exposure to environmental hazards will destroy a number of ovarian primordial follicles, reduce ovarian reserve and subsequent reproductive ability. This study designed to evaluate ovarian parameters and ovarian blood flow of women living in the area of environmental crisis Shalkar city (Kazakhstan) compared to women living in Aktobe city (Kazakhstan). PATIENTS AND METHODS: 220 women in their reproductive age studied and classified into two groups; study (Shalkar) group and control (Aktobe) group. Blood sample taken from studied women during follicular phase (day 3) for hormonal level evaluation including; follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH). Studied women evaluated using trans-vaginal ultrasound (TVS) to detect antral follicle count (AFC) during follicular scan and ovarian volume (OV), ovarian blood flow (OBF) using pulsatility index (PI) during follicular scan and luteal scan. RESULTS: Both ovaries AFC was significantly less in study (Shalkar) group compared to and control (Aktobe) group (p=0.0001). Mean ovarian volume was significantly less in Shalkar group in both follicular phase and luteal phase (5.86+/-0.23 and 6.19+/-0.22Cm(3); respectively) compared to Aktobe group (6.85+/ 0.19 and 6.92+/-0.18Cm(3); respectively). In addition, mean ovarian pulsatility index was significantly high with subsequent decrease in ovarian blood flow in Shalkar group in both follicular phase and luteal phase (3.36+/-0.20 and 3.45+/ 0.19Cm/s; respectively) compared to Aktobe group (2.96+/-0.16 and 2.92+/ 0.15Cm/s; respectively). CONCLUSION: This study suggests definite environmental effect on ovarian parameters as indicated by decreased AFC, decreased both follicular and luteal OV and OBF in women living in environmental crisis Shalkar group compared to Aktobe group. PMID- 26989803 TI - Noninvasive prenatal testing: more caution in counseling is needed in high risk pregnancies with ultrasound abnormalities. AB - OBJECTIVE: Non-invasive prenatal testing (NIPT) is increasingly being used in prenatal aneuploidy screening. The objective of this study was to assess the positive predictive value in our cohort of 68 cases with positive NIPT result. In addition, we wondered if the use of NIPT in cases with ultrasound abnormalities is appropriate, given the limited number of chromosomes investigated. DESIGN: We performed confirmative invasive testing using karyotyping, fluorescence in situ hybridization (FISH) and/or high-resolution chromosomal microarray analysis. RESULTS: In line with the published data, the positive NIPT result was confirmed in 64.7% of cases. Inconclusive and negative NIPT results followed by cytogenetically pathologic findings were encountered in three and in five cases, respectively. Four of the five fetuses with negative NIPT but pathologic cytogenetic findings were born with several malformations and diagnosed right after birth with severe genetic conditions. Of note, in all of those four cases, NIPT was offered despite the finding of major fetal ultrasound abnormalities and despite the fact that the family would not have opposed invasive testing or pregnancy termination. CONCLUSION: More education of health care providers and caution in counseling and interpretation of test results are needed in order to meet the challenges that this new test, which enriches our diagnostic options in prenatal testing, poses. PMID- 26989804 TI - L-Proline Derived Bifunctional Organocatalysts: Enantioselective Michael Addition of Dithiomalonates to trans-beta-Nitroolefins. AB - A series of novel L-proline derived tertiary amine bifunctional organocatalysts 9 are reported, which were applied to the asymmetric Michael addition of dithiomalonates 2 to trans-beta-nitroolefins 1. The reaction proceeded in high yields (up to 99%) with high enantioselectivities (up to 97% ee). The synthetic utility of this methodology was demonstrated in the short synthesis of (R) phenibut in high yield. PMID- 26989805 TI - Incremental health care costs for chronic pain in Ontario, Canada: a population based matched cohort study of adolescents and adults using administrative data. AB - Little is known about the economic burden of chronic pain and how chronic pain affects health care utilization. We aimed to estimate the annual per-person incremental medical cost and health care utilization for chronic pain in the Ontario population from the perspective of the public payer. We performed a retrospective cohort study using Ontario health care databases and the electronically linked Canadian Community Health Survey (CCHS) from 2000 to 2011. We identified subjects aged >=12 years from the CCHS with chronic pain and closely matched them to individuals without pain using propensity score matching methods. We used linked data to determine mean 1-year per-person health care costs and utilization for each group and mean incremental cost for chronic pain. All costs are reported in 2014 Canadian dollars. After matching, we had 19,138 pairs of CCHS respondents with and without chronic pain. The average age was 55 years (SD = 18) and 61% were female. The incremental cost to manage chronic pain was $1742 per person (95% confidence interval [CI], $1488-$2020), 51% more than the control group. The largest contributor to the incremental cost was hospitalization ($514; 95% CI, $364-$683). Incremental costs were the highest in those with severe pain ($3960; 95% CI, $3186-$4680) and in those with most activity limitation ($4365; 95% CI, $3631-$5147). The per-person cost to manage chronic pain is substantial and more than 50% higher than a comparable patient without chronic pain. Costs are higher in people with more severe pain and activity limitations. PMID- 26989806 TI - Making sense of sensory profiles. PMID- 26989807 TI - New horizons in osteoporosis therapies. AB - Efficient therapies are available for the treatment of osteoporosis, however, there are still unmet needs. Anti-resorptive therapies only increase bone mineral density to a certain extent and reduce the risk of non-vertebral fractures by 20%, only one anabolic option is available-the effect of which levels off over time, and the evidence for combination therapy targeting both resorption and formation is limited. The current review will focus on emerging treatments of osteoporosis with the potential of enhanced anabolic effects (romosozumab and abaloparatide) or uncoupling of resorption and formation (odanacatib and romosozumab) as well as the effect of combination therapy. PMID- 26989809 TI - Conductive Fabric-Based Stretchable Hybridized Nanogenerator for Scavenging Biomechanical Energy. AB - We demonstrate a stretchable hybridized nanogenerator based on a highly conductive fabric of glass fibers/silver nanowires/polydimethylsiloxane. Including a triboelectric nanogenerator and an electromagnetic generator, the hybridized nanogenerator can deliver output voltage/current signals from stretchable movements by both triboelectrification and electromagnetic induction, maximizing the efficiency of energy scavenging from one motion. Compared to the individual energy-harvesting units, the hybridized nanogenerator has a better charging performance, where a 47 MUF capacitor can be charged to 2.8 V in only 16 s. The hybridized nanogenerator can be integrated with a bus grip for scavenging wasted biomechanical energy from human body movements to solve the power source issue of some electric devices in the pure electric bus. PMID- 26989808 TI - Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation. AB - For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT. PMID- 26989810 TI - Development of a Tool to Assess Basic Competency in the Performance of Rigid Bronchoscopy. AB - RATIONALE: Rigid bronchoscopy is increasingly used by pulmonologists for the management of central airway disorders. However, an assessment tool to evaluate the competency of operators in the performance of this technique has not been developed. We created the Rigid Bronchoscopy Tool for Assessment of Skills and Competence (RIGID-TASC) to serve as an objective, competency-oriented assessment tool of basic rigid bronchoscopic skills, including rigid bronchoscopic intubation and central airway navigation. OBJECTIVES: To assess whether RIGID TASC scores accurately distinguish the basic rigid bronchoscopy skills of novice, intermediate, and expert operators, and to determine whether RIGID-TASC has adequate interrater reliability when used by different independent testers. METHODS: At two academic medical centers in the United States, 30 physician volunteers were selected in three categories: 10 novices at rigid bronchoscopy (performed at least 50 flexible, but no rigid, bronchoscopies), 10 operators with intermediate experience (performed 5-20 rigid bronchoscopies), and 10 experts (performed >=100 rigid bronchoscopies). Participants included pulmonary and critical care fellows, interventional pulmonology fellows, and faculty interventional pulmonologists. Each subject then performed rigid bronchoscopic intubation and navigation on a manikin, while being scored independently by two testers, using RIGID-TASC. MEASUREMENTS AND MAIN RESULTS: Mean scores for three categories (novice, intermediate, and expert) were 58.10 (+/-4.6 [SE]), 78.15 (+/ 3.8), and 94.40 (+/-1.1), respectively. There was significant difference between novice and intermediate (20.05, 95% confidence interval [CI] = 7.77-32.33, P = 0.001), and intermediate and expert (16.25, 95% CI = 3.97-28.53, P = 0.008) operators. The interrater reliability (intraclass correlation coefficient) between the two testers was high (r = 0.95, 95% CI = 0.90-0.98). CONCLUSIONS: RIGID-TASC showed evidence of construct validity and interrater reliability in this setting and group of subjects. It can be used to reliably and objectively score and classify operators from novice to expert in basic rigid bronchoscopic intubation and navigation. PMID- 26989811 TI - Characterisation of the impact of open biomass burning on urban air quality in Brisbane, Australia. AB - Open biomass burning from wildfires and the prescribed burning of forests and farmland is a frequent occurrence in South-East Queensland (SEQ), Australia. This work reports on data collected from 10 to 30 September 2011, which covers the days before (10-14 September), during (15-20 September) and after (21-30 September) a period of biomass burning in SEQ. The aim of this project was to comprehensively quantify the impact of the biomass burning on air quality in Brisbane, the capital city of Queensland. A multi-parameter field measurement campaign was conducted and ambient air quality data from 13 monitoring stations across SEQ were analysed. During the burning period, the average concentrations of all measured pollutants increased (from 20% to 430%) compared to the non burning period (both before and after burning), except for total xylenes. The average concentration of O3, NO2, SO2, benzene, formaldehyde, PM10, PM2.5 and visibility-reducing particles reached their highest levels for the year, which were up to 10 times higher than annual average levels, while PM10, PM2.5 and SO2 concentrations exceeded the WHO 24-hour guidelines and O3 concentration exceeded the WHO maximum 8-hour average threshold during the burning period. Overall spatial variations showed that all measured pollutants, with the exception of O3, were closer to spatial homogeneity during the burning compared to the non-burning period. In addition to the above, elevated concentrations of three biomass burning organic tracers (levoglucosan, mannosan and galactosan), together with the amount of non-refractory organic particles (PM1) and the average value of f60 (attributed to levoglucosan), reinforce that elevated pollutant concentration levels were due to emissions from open biomass burning events, 70% of which were prescribed burning events. This study, which is the first and most comprehensive of its kind in Australia, provides quantitative evidence of the significant impact of open biomass burning events, especially prescribed burning, on urban air quality. The current results provide a solid platform for more detailed health and modelling investigations in the future. PMID- 26989812 TI - Long-term exposure to fine particulate matter and incidence of diabetes in the Danish Nurse Cohort. AB - AIMS/HYPOTHESIS: It has been suggested that air pollution may increase the risk of type 2 diabetes but data on particulate matter with diameter <2.5MUm (PM2.5) are inconsistent. We examined the association between long-term exposure to PM2.5 and diabetes incidence. METHODS: We used the Danish Nurse Cohort with 28,731 female nurses who at recruitment in 1993 or 1999 reported information on diabetes prevalence and risk factors, and obtained data on incidence of diabetes from National Diabetes Register until 2013. We estimated annual mean concentrations of PM2.5, particulate matter with diameter <10MUm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at their residence since 1990 using a dispersion model and examined the association between the 5-year running mean of pollutants and diabetes incidence using a time-varying Cox regression. RESULTS: Of 24,174 nurses 1137 (4.7%) developed diabetes. We detected a significant positive association between PM2.5 and diabetes incidence (hazard ratio; 95% confidence interval: 1.11; 1.02-1.22 per interquartile range of 3.1MUg/m(3)), and weaker associations for PM10 (1.06; 0.98-1.14 per 2.8MUg/m(3)), NO2 (1.05; 0.99-1.12 per 7.5MUg/m(3)), and NOx (1.01; 0.98-1.05 per 10.2MUg/m(3)) in fully adjusted models. Associations with PM2.5 persisted in two-pollutant models. Associations with PM2.5 were significantly enhanced in never smokers (1.24; 1.09-1.42), and augmented in obese (1.25; 1.06-1.47) and subjects with myocardial infarction (1.32; 0.86-2.02), but without significant interaction. CONCLUSIONS/INTERPRETATION: Fine particulate matter may the most relevant pollutant for diabetes development among women, and non-smokers, obese women, and heart disease patients may be most susceptible. PMID- 26989813 TI - Let-7a modulates particulate matter (<= 2.5 MUm)-induced oxidative stress and injury in human airway epithelial cells by targeting arginase 2. AB - Epidemiological studies show that particulate matter (PM) with an aerodynamic diameter <= 2.5 MUm (PM2.5) is associated with cardiorespiratory diseases via the induction of excessive oxidative stress. However, the precise mechanism underlying PM2.5-mediated oxidative stress injury has not been fully elucidated. Accumulating evidence has indicated the microRNA let-7 family might play a role in PM-mediated pathological processes. In this study, we investigated the role of let-7a in oxidative stress and cell injury in human bronchial epithelial BEAS2B (B2B) cells after PM2.5 exposure. The let-7a level was the most significantly decreased in B2B cells after PM2.5 exposure. The overexpression of let-7a suppressed intracellular reactive oxygen species levels and the percentage of apoptotic cells after PM2.5 exposure, while the let-7a level decreased arginase 2 (ARG2) mRNA and protein levels in B2B cells by directly targeting the ARG2 3' untranslated region. ARG2 expression was upregulated in B2B cells during PM2.5 treatment, and ARG2 knockdown could remarkably reduce oxidative stress and cellular injury. Moreover, its restoration could abrogate the protective effects of let-7a against PM2.5-induced injury. In conclusion, let-7a decreases and ARG2 increases resulting from PM2.5 exposure may exacerbate oxidative stress, cell injury and apoptosis of B2B cells. The let-7a/ARG2 axis is a likely therapeutic target for PM2.5-induced airway epithelial injury. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26989814 TI - Material Gradients in Stretchable Substrates toward Integrated Electronic Functionality. AB - The approach toward a stretchable electronic substrate employs multiple soft polymer layers patterned around silicon chips, which act as surrogates for conventional electronics chips, to create a controllable stiffness gradient. Adding just one intermediate polymer layer results in a six-fold increase in the strain failure threshold enabling the substrate to be stretched to over twice its length before delamination occurs. PMID- 26989815 TI - Invention of a novel photodynamic therapy for tumors using a photosensitizing PI3K inhibitor. AB - XL147 (SAR245408, pilaralisib), an ATP-competitive pan-class I phosphoinositide 3 kinase (PI3K) inhibitor, is a promising new anticancer drug. We examined the effect of the PI3K inhibitor on PC3 prostate cancer cells under a fluorescence microscope and found that XL147-treated cancer cells are rapidly injured by blue wavelength (430 nm) light irradiation. During the irradiation, the cancer cells treated with 0.2-2 MUM XL147 showed cell surface blebbing and cytoplasmic vacuolation and died within 15 min. The extent of cell injury/death was dependent on the dose of XL147 and the light power of the irradiation. These findings suggest that XL147 might act as a photosensitizing reagent in photodynamic therapy (PDT) for cancer. Moreover, the cytotoxic effect of photosensitized XL147 was reduced by pretreatment with other ATP-competitive PI3K inhibitors such as LY294002, suggesting that the cytotoxic effect of photosensitized XL147 is facilitated by binding to PI3K in cells. In a single-cell illumination analysis using a fluorescent probe to identify reactive oxygen species (ROS), significantly increased ROS production was observed in the XL147-treated cells when the cell was illuminated with blue light. Taken together, it is conceivable that XL147, which is preferentially accumulated in cancer cells, could be photosensitized by blue light to produce ROS to kill cancer cells. This study will open up new possibilities for PDT using anticancer drugs. PMID- 26989816 TI - TNF-alpha Induces Caspase-1 Activation Independently of Simultaneously Induced NLRP3 in 3T3-L1 Cells. AB - The intracellular cysteine protease caspase-1 is critically involved in obesity induced inflammation in adipose tissue. A substantial body of evidence from immune cells, such as macrophages, has shown that caspase-1 activation depends largely on a protein complex, called the NLRP3 inflammasome, which consists of the NOD-like receptor (NLR) family protein NLRP3, the adaptor protein ASC, and caspase-1 itself. However, it is not fully understood how caspase-1 activation is regulated within adipocytes upon inflammatory stimuli. In this study, we show that TNF-alpha-induced activation of caspase-1 is accompanied by robust induction of NLRP3 in 3T3-L1 adipocytes but that caspase-1 activation may not depend on the NLRP3 inflammasome. Treatment of 3T3-L1 cells with TNF-alpha induced mRNA expression and activation of caspase-1. Although the basal expression of NLRP3 and ASC was undetectable in unstimulated cells, TNF-alpha strongly induced NLRP3 expression but did not induce ASC expression. Interestingly, inhibitors of the ERK MAP kinase pathway strongly suppressed NLRP3 expression but did not suppress the expression and activation of caspase-1 induced by TNF-alpha, suggesting that NLRP3 is dispensable for TNF-alpha-induced caspase-1 activation. Moreover, we did not detect the basal and TNF-alpha-induced expression of other NLR proteins (NLRP1a, NLRP1b, and NLRC4), which do not necessarily require ASC for caspase-1 activation. These results suggest that TNF-alpha induces caspase-1 activation in an inflammasome-independent manner in 3T3-L1 cells and that the ERK-dependent expression of NLRP3 may play a role independently of its canonical role as a component of inflammasomes. J. Cell. Physiol. 231: 2761-2767, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26989817 TI - Comparison between SACH foot and a new multiaxial prosthetic foot during walking in hypomobile transtibial amputees: physiological responses and functional assessment. AB - BACKGROUND: The most prescribed prosthetic foot for hypomobile transtibial amputees (TTAs) is the solid ankle cushion heel (SACH). Recently, the new 1M10 Adjust (Ottobock, Duderstadt, Germany) has been designed for hypomobile TTAs. No studies are available about the physiological responses to walking with 1M10 Adjust or about the related energy cost of walking (ECW). The aim of this study was to assess physiological responses to walking with 1M10 Adjust and with SACH in low-mobility TTAs and their ECW, and to compare 1M10 Adjust and SACH for physiological responses, ECW, relative perceived effort and satisfaction (SATPRO) using the prosthesis. DESIGN: Observational study. SETTING: The study was conducted in the outpatient rehabilitation unit of a rehabilitation center. POPULATION: Twenty hypomobile unilateral TTAs were enrolled. Amputees who ranged K-levels 1 or 2 were defined. METHODS: TTAs performed two over ground walking tests in two separate days, with an interval time in between of 30 days. TTAs performed the first walking test wearing their habitual SACH foot; the second walking test fitting the 1M10 Adjust, after 30 days of its use. During walking tests, TTAs walked back and forth for 6 minutes at self-selected walking speed (SSWS) and physiological data were collected. At the end of each walking test, the relative perceived effort was assessed by Borg scale. Finally, SATPRO questionnaire was administered. RESULTS: Twenty TTAs (17 males) were enrolled (mean age, body mass and height were 66.6+/-6.7 years, 78.5+/-13.2 kg, and 168.5+/-7.5 cm, respectively): 19 had a K-level 2 and one had a K-level 1. Physiological responses using SACH or 1M10 Adjust foot did not show statistical differences. ECW, SSWS and relative perceived effort significantly improved using the 1M10 Adjust. Satisfaction with 1M10 Adjust was significantly greater than with SACH. CONCLUSIONS: TTAs showed a significant improvement in ECW, relative perceived effort and SATPRO with 1M10 Adjust than with SACH. This suggests that 1M10 Adjust foot could be a good choice for hypomobile TTAs. CLINICAL REHABILITATION IMPACT: The better prosthetic performance provided by 1M10 Adjust foot during gait could improve mobility in TTAs with low mobility contributing to prevent comorbidity deriving from sedentary lifestyle. With its long-term benefits, 1M10 Adjust could contribute to a better quality of life. PMID- 26989818 TI - The effect of manipulation plus massage therapy versus massage therapy alone in people with tension-type headache. A randomized controlled clinical trial. AB - BACKGROUND: Manipulative techniques have shown promising results for relief of tension-type headache (TTH), however prior studies either lacked a control group, or suffered from poor methodological quality. The aim of this study was to compare the effect of spinal manipulation combined with massage versus massage alone on range of motion of the cervical spine, headache frequency, intensity and disability in patients with TTH. DESIGN: Randomized, single-blinded, controlled clinical trial. SETTING: University clinic. POPULATION: We enrolled 105 subjects with TTH. METHODS: Participants were divided into two groups: 1) manipulation and massage; 2) massage only (control). Four treatment sessions were applied over four weeks. The Headache Disability Inventory (HDI) and range of upper cervical and cervical motion were evaluated at baseline, immediately after the intervention and at a follow-up, 8 weeks after completing the intervention. RESULTS: Both groups demonstrated a large (f=1.22) improvement on their HDI scores. Those that received manipulation reported a medium-sized reduction (f=0.33) in headache frequency across all data points (P<0.05) compared to the control group. Both groups showed a large within-subject effect for upper cervical extension (f=0.62), a medium-sized effect for cervical extension (f=0.39), and large effects for upper cervical (f=1.00) and cervical (f=0.27) flexion. The addition of manipulation resulted in larger gains of upper cervical flexion range of motion, and this difference remained stable at the follow-up. CONCLUSIONS: These findings support the benefit of treating TTH with either massage or massage combined with a manipulative technique. However, the addition of manipulative technique was more effective for increasing range of motion of the upper cervical spine and for reducing the impact of headache. CLINICAL REHABILITATION IMPACT: Although massage provided relief of headache in TTH sufferers, when combined with cervical manipulation, there was a stronger effect on range of upper cervical spine motion. PMID- 26989819 TI - Linear endobronchial and endoesophageal ultrasound: a practice change in thoracic medicine. AB - PURPOSE OF REVIEW: Linear endosonography, including intrathoracic lymph nodal sampling by endobronchial ultrasound with transbronchial needle aspiration (EBUS TBNA) and endoesophageal ultrasound fine-needle aspiration (EUS-FNA), has an important role in the diagnosing and staging of lung cancer. Furthermore, endosonography is applied in the mediastinal evaluation of sarcoidosis, lymphoma, cysts, and nodal metastases of extrathoracic malignancies. Endosonography-related complications as well as sedation and training strategies are discussed. The purpose of this review is to summarize current practice, recent advances, and future directions. RECENT FINDINGS: Lung cancer guidelines recommend endosonography - above mediastinoscopy - as the initial test for mediastinal nodal tissue staging. By introducing the EBUS-scope into the esophagus (EUS-B) - following an EBUS procedure - the complete mediastinum and the left adrenal gland can be investigated in a single scope procedure by one operator. In patients with suspected stage I/II sarcoidosis, EBUS-TBNA/EUS-FNA is the test with the highest granuloma detection rate. Diagnosing (recurrent) lymphoma is an increasingly accepted indication for endosonography. Systematic surveys showed that endosonography has a low complication rate. Simulator-based training and assessment tools measuring competency are important instruments to provide standardized and optimal implementation. SUMMARY: Endosonography is generally accepted as a powerful and safe diagnostic test for various diseases affecting the mediastinum. Large-scale implementation is needed. PMID- 26989820 TI - Advances in pleural diseases: what is the future for medical thoracoscopy? AB - PURPOSE OF REVIEW: Medical thoracoscopy provides the physician a window into the pleural space. The procedure allows biopsy of the parietal pleura under direct visualization with good accuracy. In addition, it achieves therapeutic goals of fluid drainage, guided chest tube placement, and pleurodesis. RECENT FINDINGS: Comparable diagnostic yield is achieved with the flexi-rigid pleuroscope even though pleural biopsies are smaller using the flexible forceps as compared to rigid thoracoscopy. Flexi-rigid pleuroscopy is extremely well tolerated and can be performed safely as an outpatient procedure. Biopsy quality can be further enhanced with accessories that are compatible with the flex-rigid pleuroscope such as the insulated tip knife and cryoprobe. SUMMARY: With more sensitive tools to image the pleura such as contrast-enhanced computed tomography, MRI, ultrasonography, PET, increased yield with image-guided biopsy as well as advances in cytopathology, what lies in the future for medical thoracoscopy remains to be seen. However, it is the authors' opinion that medical thoracoscopy will evolve with time, complement novel techniques, and continue to play a pivotal role in the evaluation of pleuropulmonary diseases. PMID- 26989821 TI - Transbronchial cryobiopsy in diffuse parenchymal lung diseases. AB - PURPOSE OF REVIEW: The diagnostic yield of conventional transbronchial lung biopsy varies among various parenchymal lung diseases: in pulmonary sarcoidosis and lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients; this method is considered inadequate, however, in identifying more complex histological patterns such as usual interstitial pneumonitis or nonspecific interstitial pneumonitis, mainly because the specimens are tiny and the interpretation is confounded by crush artifacts. Recently, the use of cryoprobes has achieved a significant impact on this issue. This review is about this promising application of cryobiopsy in the diagnostic process of diffuse parenchymal lung diseases. RECENT FINDINGS: Recent studies document that with transbronchial cryobiopsies, the diagnosis of usual interstitial pneumonitis can be made confidently by pathologists with a good interobserver agreement. Pneumothorax is the main complication (reported in up to one-quarter of cases in some series); bronchial bleeding is usually controlled using Fogarty balloon. SUMMARY: Transbronchial cryobiopsy is a promising new technique that may become a valid alternative to surgical lung biopsy in the near feature. PMID- 26989822 TI - Host-directed therapies for antimicrobial resistant respiratory tract infections. AB - PURPOSE OF REVIEW: Antimicrobial-resistant respiratory tract infections (AMR RTIs) are increasing, presenting important management challenges worldwide. Current management of AMR-RTI patients focuses on pathogen-directed antimicrobial treatment. Overt lung inflammation, parenchymal damage, and ineffective immune activation perpetrate increased patient morbidity and mortality. Immunomodulatory and tissue-regenerative host-directed therapies (HDT) may improve treatment outcomes. HDTs under investigation for improving AMR-RTI treatment outcomes are reviewed. RECENT FINDINGS: Various HDTs are being developed or evaluated for adjunctive AMR-RTI treatment. alpha-1 antitrypsin was shown to reduce Pseudomonas aeruginosa burden in the airways of cystic fibrosis patients. Cellular therapy by reinfusing autologous bone marrow-derived MSCs into MDR/XDR-TB patients shows promise, whereas adjunctive T cell-based therapies are considered. Cytotoxic therapy using etoposide, a topoisomerase II-inhibiting anticancer drug extends survival of patients with severe influenza H1N1 infection-induced hemophagocytic lymphohistiocytosis. Two other novel HDT candidates, DAS181 and resveratrol show antiinfluenza effects. Novel kinase inhibitors SB203580 (MAPK-2 antagonist) and LY294002 (phosphoinositide-3 kinases antagonist) exhibit promising anti-MERS-CoV activity. Palivizumab, an anti-RSV monoclonal antibody, effectively prevents RSV infection in high-risk paediatric populations. T-cell therapy is currently considered for adjunctive HDT of azole-resistant pulmonary aspergillosis. SUMMARY: Novel HDTs may revolutionize future treatment regimens for AMR-RTIs. Well designed multisite clinical trials are now necessary to accelerate progress. PMID- 26989823 TI - Phoneme and Word Scoring in Speech-in-Noise Audiometry. AB - PURPOSE: Understanding speech in background noise is difficult for many individuals; however, time constraints have limited its inclusion in the clinical audiology assessment battery. Phoneme scoring of words has been suggested as a method of reducing test time and variability. The purposes of this study were to establish a phoneme scoring rubric and use it in testing phoneme and word perception in noise in older individuals and individuals with hearing impairment. METHOD: Words were presented to 3 participant groups at 80 dB in speech-shaped noise at 7 signal-to-noise ratios (-10 to 35 dB). Responses were scored for words and phonemes correct. RESULTS: It was not surprising to find that phoneme scores were up to about 30% better than word scores. Word scoring resulted in larger hearing loss effect sizes than phoneme scoring, whereas scoring method did not significantly modify age effect sizes. There were significant effects of hearing loss and some limited effects of age; age effect sizes of about 3 dB and hearing loss effect sizes of more than 10 dB were found. CONCLUSION: Hearing loss is the major factor affecting word and phoneme recognition with a subtle contribution of age. Phoneme scoring may provide several advantages over word scoring. A set of recommended phoneme scoring guidelines is provided. PMID- 26989824 TI - Unusual Cause of Hemodynamic Collapse in Infective Endocarditis. PMID- 26989825 TI - New models of care in IBD in changing times. PMID- 26989826 TI - Heat, Human Performance, and Occupational Health: A Key Issue for the Assessment of Global Climate Change Impacts. AB - Ambient heat exposure is a well-known health hazard, which reduces human performance and work capacity at heat levels already common in tropical and subtropical areas. Various health problems have been reported. Increasing heat exposure during the hottest seasons of each year is a key feature of global climate change. Heat exhaustion and reduced human performance are often overlooked in climate change health impact analysis. Later this century, many among the four billion people who live in hot areas worldwide will experience significantly reduced work capacity owing to climate change. In some areas, 30 40% of annual daylight hours will become too hot for work to be carried out. The social and economic impacts will be considerable, with global gross domestic product (GDP) losses greater than 20% by 2100. The analysis to date is piecemeal. More analysis of climate change-related occupational health impact assessments is greatly needed. PMID- 26989827 TI - Documenting the Effects of Armed Conflict on Population Health. AB - War and other forms of armed conflict have profound adverse effects on population health. It is important to document these effects to inform the general public and policy makers about the consequences of armed conflict, provide services to meet the needs of affected populations, protect human rights and document violations of international humanitarian law, and help to prevent future armed conflict. Documentation can be accomplished with surveillance, epidemiological surveys, and rapid assessment. Challenges include inadequate or absent data systems, social breakdown, forced migration, reporting biases, and the fog of war. The adverse effects of the Iraq War on population health demonstrate how the effects of armed conflict on population health can be documented. We recommend the establishment of an independent mechanism, operated by the United Nations or a multilateral organization, to investigate and document the effects of armed conflict on population health. PMID- 26989829 TI - Sugar-Sweetened Beverages and Children's Health. AB - Temporal trends in the epidemic of childhood obesity have been paralleled by increases in the consumption of sugar-sweetened beverages (SSB) during childhood. Consumption has increased dramatically over the past several decades in all age ranges, with some moderation over the past 10 years. Evidence from cross sectional, longitudinal, and interventional studies supports links between SSB consumption in childhood and unhealthy weight gain, as well as other untoward health outcomes. These data have stimulated public health efforts to curtail consumption as a means of improving childhood weight status and related health outcomes. Reducing ready access to SSBs, changing the message environment to which children are exposed, and replacing SSBs with healthier beverages have had moderate success in decreasing SSB consumption and curbing unhealthy weight gain. PMID- 26989830 TI - Visible and Invisible Trends in Black Men's Health: Pitfalls and Promises for Addressing Racial, Ethnic, and Gender Inequities in Health. AB - Over the past two decades, there has been growing interest in improving black men's health and the health disparities affecting them. Yet, the health of black men consistently ranks lowest across nearly all groups in the United States. Evidence on the health and social causes of morbidity and mortality among black men has been narrowly concentrated on public health problems (e.g., violence, prostate cancer, and HIV/AIDS) and determinants of health (e.g., education and male gender socialization). This limited focus omits age-specific leading causes of death and other social determinants of health, such as discrimination, segregation, access to health care, employment, and income. This review discusses the leading causes of death for black men and the associated risk factors, as well as identifies gaps in the literature and presents a racialized and gendered framework to guide efforts to address the persistent inequities in health affecting black men. PMID- 26989828 TI - Preventing Obesity Across Generations: Evidence for Early Life Intervention. AB - To prevent the intergenerational transfer of obesity and end the current epidemic, interventions are needed across the early life stages, from preconception to prenatal to infancy through the age of 2 years. The foundation for obesity is laid in early life by actions and interactions passed from parent to child that have long-lasting biologic and behavioral consequences. The purpose of this paper is to examine the best evidence about (a) factors in parents and offspring that promote obesity during the early life stages, (b) the social determinants and dimensions of obesity in early life, (c) promising and effective interventions for preventing obesity in early life, and (d) opportunities for future research into strategies to disrupt the intergenerational cycle of obesity that begins early in life. The pathway for halting the intergenerational obesity epidemic requires the discovery and development of evidence-based interventions that can act across multiple dimensions of influence on early life. PMID- 26989831 TI - Opportunities for Palliative Care in Public Health. AB - In May 2014, the World Health Assembly, of the World Health Organization (WHO), unanimously adopted a palliative care (PC) resolution, which outlines clear recommendations to the United Nations member states, such as including PC in national health policies and in the undergraduate curricula for health care professionals, and highlights the critical need for countries to ensure that there is an adequate supply of essential PC medicines, especially those needed to alleviate pain. This resolution also carries great challenges: Every year over 20 million patients (of which 6% are children) need PC at the end of life (EOL). However, in 2011, approximately three million patients received PC, and only one in ten people in need is currently receiving it. We describe this public health situation and systems failure, the history and evolution of PC, and the components of the WHO public health model. We propose a role for public health for PC integration in community settings to advance PC and relieve suffering in the world. PMID- 26989832 TI - Detection of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction. AB - BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma caused by oncogenic HPV (HPV-OPSCC) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV-16 E6 and E7 oncoproteins or by cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 (p16) immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. We aimed to validate this method for the detection of HPV-16 E6 and E7 in HPV-OPSCC. METHODS: Participants were recruited from January 2015-November 2015 at initial presentation to the University of Alberta Head and Neck Oncology Clinic. RNA was extracted, purified and quantified from prospectively collected participant tissues, and ddPCR was performed with fluorescent probes detecting HPV-16 E6 and E7. Results from ddPCR were compared with p16 IHC performed by clinical pathology as standard of care. RESULTS: Head and neck tissues were prospectively obtained from 68 participants including 29 patients with OPSCC, 29 patients with non-OPSCC and 10 patients without carcinoma. 79.2% of patients with OPSCC were p16 positive. The sensitivity and specificity of ddPCR HPV E6/E7 compared with p16 IHC in OPSCC was 91.3 and 100%, respectively. The amount of target RNA used was <=1 ng, 20-50 times lower than reported by other for RT-qPCR HPV E6/E7. CONCLUSIONS: The ddPCR of HPV E6/E7 is a novel and highly specific method of detecting HPV-16 in OPSCC. Cancer 2016;122:1544-51. (c) 2016 American Cancer Society. PMID- 26989833 TI - The effect of self-focused attention and mood on appearance dissatisfaction after mirror-gazing: An experimental study. AB - BACKGROUND AND OBJECTIVES: Self-focused attention is hypothesized to be a maintenance factor in body dysmorphic disorder (BDD). The aim of this study was to use an experimental paradigm to test this hypothesis by studying the effect of self-focused attention during mirror-gazing on appearance dissatisfaction. METHODS: An experimental group design was used, in which 173 women were randomly allocated to one of three conditions before mirror-gazing for 2 min: (a) external focus of attention, (b) self-focus of attention, and (c) self-focus of attention with a negative mood induction. RESULTS: After mirror-gazing, participants across all groups rated themselves as being more dissatisfied with their appearance. In both the self-focus conditions, there was an increase in sadness from pre to post mirror gazing, and there was a significant difference in focus of attention for participants in the self-focused, mood-induced group from pre to post manipulation, suggesting mood induction had more of an effect than focus of attention. LIMITATIONS: (1) there was no condition involving an external focus with a negative mood induction, and (2) due to the level of information provided to patients on the nature of the task, we cannot rule out demand characteristics as an influencing factor on our results. CONCLUSIONS: Self-focused attention during mirror-gazing may act indirectly to increase appearance dissatisfaction via the effect of negative mood. Further studies are required to establish the relative contribution of self-focused attention and negative mood to increases in appearance dissatisfaction as a function of mirror-gazing. PMID- 26989835 TI - Myoepithelial carcinoma on the right shoulder: Case report with published work review. AB - Myoepithelial carcinoma is a malignant tumor that can differentiate towards myoepithelial cells and commonly occur in the salivary glands. There have been only a few reports of primary cutaneous myoepithelial carcinoma; however, most cases showed subcutaneous involvement and could also be diagnosed as soft tissue myoepithelial carcinoma arising from the subcutis with dermal involvement. It may thus be impossible to distinguish a primary cutaneous from a soft tissue myoepithelial carcinoma. Herein, we describe a case of myoepithelial carcinoma on the shoulder in an 85-year-old Japanese woman. The tumor was located in the whole dermis and subcutis; therefore, it could be diagnosed as either a cutaneous or soft tissue myoepithelial carcinoma. We reviewed previous cases of primary cutaneous and soft tissue myoepithelial carcinomas and compared their clinical and immunohistological features. We found no obvious differences in anatomical distribution or immunohistochemical findings. However, the recurrence rate of cutaneous myoepithelial carcinomas seems to be lower than that of soft tissue carcinomas. Such a difference may be attributable to the adequate surgical margin in cutaneous carcinomas compared with the deep-seated soft tissue carcinomas. The metastatic frequency did not significantly differ between the two types. Although we could summarize from only a small number of cases, these results indicate the difficulty in distinguishing between cutaneous and soft tissue myoepithelial carcinomas; furthermore, it may not be suitable to distinguish them on the basis of aggressive behavior. PMID- 26989836 TI - More inclusive bipolar mixed depression definitions by requiring fewer non overlapping mood elevation symptoms. AB - OBJECTIVE: Assess strengths and limitations of mixed bipolar depression definitions made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by requiring fewer than three 'non-overlapping' mood elevation symptoms (NOMES). METHOD: Among bipolar disorder (BD) out-patients assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using less inclusive (>=3 NOMES, DSM-5), more inclusive (>=2 NOMES), and most inclusive (>=1 NOMES) definitions. RESULTS: Among 153 depressed BD, compared to less inclusive DSM-5 threshold, our more and most inclusive thresholds, yielded approximately two- and five-fold higher mixed depression rates (7.2%, 15.0%, and 34.6% respectively), and important statistically significant clinical correlates for mixed compared to pure depression (e.g. more lifetime anxiety disorder comorbidity, more current irritability), which were not significant using the DSM-5 threshold. CONCLUSION: Further studies assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including assessing the extent to which enhanced statistical power vs. other factors contributes to more vs. less inclusive mixed bipolar depression thresholds having more statistically significant clinical correlates, and whether 'overlapping' mood elevation symptoms should be counted. PMID- 26989837 TI - Effects of State Cervical Cancer Insurance Mandates on Pap Test Rates. AB - OBJECTIVE: To evaluate the effects of state insurance mandates requiring insurance plans to cover Pap tests, the standard screening for cervical cancer that is recommended for nearly all adult women. DATA SOURCES: Individual-level data on 600,000 women age 19-64 from the CDC's Behavioral Risk Factor Surveillance System. STUDY DESIGN: Twenty-four states adopted state mandates requiring private insurers in the state to cover Pap tests from 1988 to 2000. We performed a difference-in-differences analysis comparing within-state changes in Pap test rates before and after adoption of a mandate, controlling for the associated changes in other states that did not adopt a mandate. PRINCIPAL FINDINGS: Difference-in-differences estimates indicated that the Pap test mandates significantly increased past 2-year cervical cancer screenings by 1.3 percentage points, with larger effects for Hispanic and non-Hispanic white women. These effects are plausibly concentrated among insured women. CONCLUSIONS: Mandating more generous insurance coverage for even inexpensive, routine services with already high utilization rates such as Pap tests can significantly further increase utilization. PMID- 26989838 TI - Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury. AB - Cellular transplantation strategies utilizing intraspinal injection of mesenchymal progenitor cells (MPCs) have been reported as beneficial for spinal cord injuries. However, intraspinal injection is not only technically challenging, but requires invasive surgical procedures for patients. Therefore, we investigated the feasibility and potential benefits of noninvasive intravenous injection of MPCs in two models of cervical spinal cord injury, unilateral C5 contusion and complete unilateral C5 hemisection. MPCs isolated from green fluorescence protein (GFP)-luciferase transgenic mice compact bone (1 * 10(6) cells), or vehicle Hank's Buffered Saline Solution (HBSS), were intravenously injected via the tail vein at D1, D3, D7, D10, or D14. Transplanted MPCs were tracked via bioluminescence imaging. Live in vivo imaging data showed that intravenously injected MPCs accumulate in the lungs, confirmed by postmortem bioluminescence signal-irrespective of the time of injection or injury model. The results showed a rapid, positive modulation of the inflammatory response providing protection to the injured spinal cord tissue. Histological processing of the lungs showed GFP(+) cells evenly distributed around the alveoli. We propose that injected cells can act as cellular target decoys to an immune system primed by injury, thereby lessening the inflammatory response at the injury site. We also propose that intravenous injected MPCs modulate the immune system via the lungs through secreted immune mediators or contact interaction with peripheral organs. In conclusion, the timing of intravenous injection of MPCs is key to the success for improving function and tissue preservation following cervical spinal cord injury. Stem Cells 2016;34:1812-1825. PMID- 26989839 TI - Metabolomic analysis of survival in carbohydrate pre-fed pigs subjected to shock and polytrauma. AB - Hemorrhagic shock, a result of extensive blood loss, is a dominant factor in battlefield morbidity and mortality. Early rodent studies in hemorrhagic shock reported carbohydrate feeding prior to the induction of hemorrhagic shock decreased mortality. When repeated in our laboratory with a porcine model, carbohydrate pre-feed resulted in a 60% increase in death rate following hemorrhagic shock with trauma when compared to fasted animals (15/32 or 47% vs. 9/32 or 28%). In an attempt to explain the unexpected death rate for pre-fed animals, we further investigated the metabolic profiles of pre-fed non-survivors (n = 15) across 4 compartments (liver, muscle, serum, and urine) at specific time intervals (pre-shock, shock, and resuscitation) and compared them to pre-fed survivors (n = 17). As hypothesized, pre-fed pigs that died as a result of hemorrhage and trauma showed differences in their metabolic and physiologic profiles at all time intervals and in all compartments when compared to pre-fed survivors. Our data suggest that, although all animals were subjected to the same shock and trauma protocol, non-survivors exhibited altered carbohydrate processing as early as the pre-shock sampling point. This was evident in (for example) the higher levels of ATP and markers of greater anabolic activity in the muscle at the pre-shock time point. Based on the metabolic findings, we propose two mechanisms that connect pre-fed status to a higher death rate: (1) animals that die are more susceptible to opening of the mitochondrial permeability transition pore, a major factor in ischemia/reperfusion injury; and (2) loss of fasting-associated survival mechanisms in pre-fed animals. PMID- 26989840 TI - Effect of Aqueous Extract of the Seaweed Gracilaria domingensis on the Physicochemical, Microbiological, and Textural Features of Fermented Milks. AB - The effects of the Gracilaria domingensis seaweed aqueous extract in comparison with gelatin on the physicochemical, microbial, and textural characteristics of fermented milks processed with the mixed culture SAB 440 A, composed of Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium animalis ssp. lactis, were investigated. The addition of G. domingensis aqueous extract did not affect pH, titratable acidity, and microbial viability of fermented milks when compared with the control (with no texture modifier) and the products with added gelatin. Fermented milk with added the seaweed aqueous extract showed firmness, consistency, cohesiveness, and viscosity index at least 10% higher than those observed for the control product (P < 0.05). At 4 h of fermentation, the fermented milks with only G. domingensis extract showed a texture comparable to that observed for products containing only gelatin. At 5 h of fermentation, firmness and consistency increased significantly (P < 0.05) in products with only seaweed extract added, a behavior not observed in products with the full amount of gelatin, probably due to the differences between the interactions of these ingredients with casein during the development of the gel network throughout the acidification of milk. The G. domingensis aqueous extract appears as a promising gelatin alternative to be used as texture modifier in fermented milks and related dairy products. PMID- 26989841 TI - Acquired cholesteatoma epithelial hyperproliferation: Roles of cell proliferation signal pathways. AB - OBJECTIVES/HYPOTHESIS: To review the recent cell proliferation signal pathways in the etiopathogenesis of acquired middle ear cholesteatoma. DATA SOURCES: PubMed (to September 2015). REVIEW METHODS: Articles about cell proliferation signal pathways in the etiopathogenesis of acquired cholesteatoma and treatment advances were searched in the PubMed database, from which 73 were included in this review. RESULTS: The exact underlying cellular and molecular mechanism of acquired cholesteatoma still remains unknown. Recent research tends to regard the proliferation of cholesteatoma epithelial cells as the mechanism of cholesteatoma pathogenesis. Cell proliferation signal pathways including epidermal growth factor receptor/phosphoinositide 3-kinase/protein kinase B signal pathway, mitogen-activated protein kinase signal pathway, interleukin-6/signal transducer and activator of transcription 3 signal pathway, inhibitor of DNA binding/differentiation-1/nuclear factor-kappaB/cyclinD1 signal pathway, microRNA mediated proliferation signal pathway, and keratinocyte growth factor/keratinocyte growth factor receptor signal pathway have been proven to play important roles in acquired middle ear cholesteatoma. CONCLUSIONS: This review outlines the main biological properties of certain cell proliferation signal pathways, aiming to facilitate the development of potential therapeutic targets for intratympanic drug therapy for the nonsurgical or complementary treatment of cholesteatoma. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1923-1930, 2016. PMID- 26989842 TI - A capillary zone electrophoresis method to detect conformers and dimers of antithrombin in therapeutic preparations. AB - Antithrombin (AT) is a human plasma glycoprotein that possesses anticoagulant and anti-inflammatory properties. However, the native (active) form of AT is unstable and undergoes conformational changes, leading to latent, cleaved, and heterodimeric forms. The presence of these alternative forms mostly inactive can highly impact the quality and therapeutic activity of pharmaceutical AT preparations. We developed a capillary zone electrophoresis method, based on a neutral polyethylene oxide-coated capillary and a buffer close to physiological conditions, enabling the separation of more than eight forms of AT. Several peaks were identified as native, latent, and heterodimeric forms. The CZE method was reproducible with intraday relative standard deviations less than 0.5 and 2% for migration times and peak areas, respectively. The method was applied to the comparison of AT preparations produced by five competitive pharmaceutical companies, and statistical tests were performed. Important differences in the proportion of each form were highlighted. In particular, one AT preparation was shown to contain a high quantity of heterodimer, and two preparations contained high quantities of latent form. In addition, one AT preparation exhibited additional forms, not yet identified. PMID- 26989843 TI - Consanguinity and autosomal recessive neuromuscular disorders. PMID- 26989844 TI - Emotional responses to irony and emoticons in written language: Evidence from EDA and facial EMG. AB - While the basic nature of irony is saying one thing and communicating the opposite, it may also serve additional social and emotional functions, such as projecting humor or anger. Emoticons often accompany irony in computer-mediated communication, and have been suggested to increase enjoyment of communication. In the current study, we aimed to examine online emotional responses to ironic versus literal comments, and the influence of emoticons on this process. Participants read stories with a final comment that was either ironic or literal, praising or critical, and with or without an emoticon. We used psychophysiological measures to capture immediate emotional responses: electrodermal activity to directly measure arousal and facial electromyography to detect muscle movements indicative of emotional expressions. Results showed higher arousal, reduced frowning, and enhanced smiling for messages with rather than without an emoticon, suggesting that emoticons increase positive emotions. A tendency toward less negative responses (i.e., reduced frowning and enhanced smiling) for ironic than literal criticism, and less positive responses (i.e., enhanced frowning and reduced smiling) for ironic than literal praise suggests that irony weakens the emotional impact of a message. The present findings indicate the utility of a psychophysiological approach in studying online emotional responses to written language. PMID- 26989845 TI - The Future is Now: Reducing Psychological Distance to Increase Public Engagement with Climate Change. AB - Many people perceive climate change as psychologically distant-a set of uncertain events that might occur far in the future, impacting distant places and affecting people dissimilar to themselves. In this study, we employed construal level theory to investigate whether a climate change communication intervention could increase public engagement by reducing the psychological distance of climate change. Australian residents (N = 333) were randomly assigned to one of two treatment conditions: one framed to increase psychological distance to climate change (distal frame), and the other framed to reduce psychological distance (proximal frame). Participants then completed measures of psychological distance of climate change impacts, climate change concern, and intentions to engage in mitigation behavior. Principal components analysis indicated that psychological distance to climate change was best conceptualized as a multidimensional construct consisting of four components: geographic, temporal, social, and uncertainty. Path analysis revealed the effect of the treatment frame on climate change concern and intentions was fully mediated by psychological distance dimensions related to uncertainty and social distance. Our results suggest that climate communications framed to reduce psychological distance represent a promising strategy for increasing public engagement with climate change. PMID- 26989846 TI - Dose Timing of an Angiotensin II Receptor Blocker/Calcium Channel Blocker Combination in Hypertensive Patients With Paroxysmal Atrial Fibrillation. AB - It has long been thought that there is a close association between hypertension and atrial fibrillation (AF). However, the efficacy of an angiotensin II receptor blocker for the prevention of organ damage in hypertensive individuals with AF is still controversial. The present study was a multicentered, prospective, randomized, open-label clinical trial investigating the differences in the effect of treatment with telmisartan/amlodipine combination tablets on blood pressure (BP) levels and BP variability between morning and bedtime administration in hypertensive patients with paroxysmal AF, using ambulatory BP monitoring (ABPM) and home BP. With this treatment, the patients' 24-hour BP, nighttime BP, preawake BP, and morning BP shown by ABPM were significantly reduced, and the antihypertensive effects were similar regardless of the timing of the drug administration. The standard deviation of day-by-day home systolic BP and the maximum home systolic BP were also significantly reduced, and these effects were similar regardless of the treatment timing. The N-terminal pro-brain natriuretic peptide level was significantly decreased only in the bedtime administration group. A larger study will demonstrate whether the bedtime administration of telmisartan/amlodipine combination tablets maximizes the risk-lowering effect against AF recurrence in paroxysmal AF hypertensive patients. PMID- 26989847 TI - Selective Inhibition of PTP1B by Vitalboside A from Syzygium cumini Enhances Insulin Sensitivity and Attenuates Lipid Accumulation Via Partial Agonism to PPARgamma: In Vitro and In Silico Investigation. AB - Although antidiabetic drugs show good insulin-sensitizing property for T2DM, they also exhibit undesirable side-effects. Partial peroxisome proliferator-activated receptor gamma agonism with protein tyrosine phosphatase 1B inhibition is considered as an alternative therapeutic approach toward the development of a safe insulin sensitizer. Bioactivity-based fractionation and purification of Syzygium cumini seeds led to the isolation and identification of bifunctional Vitalboside A, which showed antidiabetic and anti-adipogenic activities, as measured by glucose uptake in L6 and 3T3-L1 adipocytes and Nile red assay. A non competitive allosteric inhibition of protein tyrosine phosphatase 1B by Vitalboside A was observed, which was confirmed by docking studies. Inhibitor studies with wortmannin and genistein showed an IRTK- and PI3K-dependent glucose uptake. A PI3K/AKT-dependent activation of GLUT4 translocation and an inactivation of GSK3beta were observed, confirming its insulin-sensitizing potential. Vitalboside A exhibited partial transactivation of peroxisome proliferator-activated receptor gamma with an increase in adiponectin secretion, which was confirmed using docking analysis. Vitalboside A is a bifunctional molecule derived from edible plant showing inhibition of PTP1B and partial agonism to peroxisome proliferator-activated receptor gamma which could be a promising therapeutic agent in the management of obesity and diabetes. PMID- 26989848 TI - Carboxylation of Phenols with CO2 at Atmospheric Pressure. AB - A convenient and efficient method for the ortho-carboxylation of phenols under atmospheric CO2 pressure has been developed. This method provides an alternative to the previously reported Kolbe-Schmitt method, which requires very high pressures of CO2 . The addition of a trisubstituted phenol has proved essential for the successful carboxylation of phenols with CO2 at standard atmospheric pressure, allowing the efficient preparation of a broad variety of salicylic acids. PMID- 26989849 TI - Melatonin attenuates postharvest physiological deterioration of cassava storage roots. AB - Melatonin reportedly increases abiotic and biotic stress tolerance in plants, but information on its in vivo effects during postharvest physiological deterioration (PPD) in cassava is limited. In this study, we investigated the effect of melatonin in regulating cassava PPD. Treatment with 500 mg/L melatonin significantly delayed cassava PPD and reduced the accumulation of hydrogen peroxide (H2O2) while increasing the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), but not ascorbate peroxidase (APX). Transcript analysis further showed that expression of copper/zinc SOD (MeCu/ZnSOD), MeCAT1, glutathione peroxidase (MeGPX), peroxidase 3 (MePX3), and glutathione S-transferases (MeGST) was higher in cassava roots sliced treated with 500 mg/L melatonin than in those not exposed to exogenous melatonin. These data demonstrate that melatonin delays cassava PPD by directly or indirectly maintaining homoeostasis of cellular reactive oxygen species (ROS). We also found that accumulation of endogenous melatonin and the transcript levels of melatonin biosynthesis genes changed dynamically during the PPD process. This finding suggested that endogenous melatonin acts as a signal modulator for maintaining cassava PPD progression and that manipulation of melatonin biosynthesis genes through genetic engineering might prevent cassava root deterioration. PMID- 26989850 TI - LETHAL MEANS ACCESS AND ASSESSMENT AMONG SUICIDAL EMERGENCY DEPARTMENT PATIENTS. AB - BACKGROUND: Reducing access to lethal means (especially firearms) might prevent suicide, but counseling of at-risk individuals about this strategy may not be routine. Among emergency department (ED) patients with suicidal ideation or attempts (SI/SA), we sought to describe home firearm access and examine ED provider assessment of access to lethal means. METHODS: This secondary analysis used data from the Emergency Department Safety Assessment and Follow-up Evaluation, a three-phase, eight-center study of adult ED patients with SI/SA (2010-2013). Research staff surveyed participants about suicide-related factors (including home firearms) and later reviewed the ED chart (including documented assessment of lethal means access). RESULTS: Among 1,358 patients with SI/SA, 11% (95% CI: 10-13%) reported >=1 firearm at home; rates varied across sites (range: 6-26%) but not over time. On chart review, 50% (95% CI: 47-52%) of patients had documentation of lethal means access assessment. Frequency of documented assessment increased over study phases (40-60%, P < .001) but was not associated with state firearm ownership rates. Among the 337 (25%, 95% CI: 23-27%) patients discharged to home, 55% (95% CI: 49-60%) had no documentation of lethal means assessment; of these, 13% (95% CI: 8-19%; n = 24) actually had >=1 firearm at home. Among all those reporting >=1 home firearm to study staff, only half (50%, 95% CI: 42-59%) had provider documentation of assessment of lethal means access. CONCLUSIONS: Among these ED patients with SI/SA, many did not have documented assessment of home access to lethal means, including patients who were discharged home and had >=1 firearm at home. PMID- 26989851 TI - Analysis of Health Care Costs in Elderly Patients with Multiple Chronic Conditions Using a Finite Mixture of Generalized Linear Models. AB - In this paper we analysed healthcare costs in a sample of elderly patients suffering from multimorbidity. On the one hand, multimorbid individuals consume a disproportionally large share of healthcare resources. On the other hand, the patient specific number and combination of co-occurring single diseases result in inhomogeneous data leading to biased estimates when using traditional regression techniques. Therefore, we applied a mixture of regressions in order to control for unobserved heterogeneity focussing on the identification of multimorbidity patterns. We used a subsample of N = 1050 patients from a multicentre prospective cohort study of randomly selected multimorbid primary care patients aged 65 to 85 years in Germany (ISRCTN 89818205) who completed a detailed questionnaire on healthcare utilization during the 6-month period preceding the interview. Disease combinations of 1047 were included. We detected four different groups of patients with regard to total costs. These groups corresponded largely to findings from the epidemiological literature. The effect of the presence of an additional disease on costs differed between groups. Moreover, two diametrically opposed cost trends were detected with respect to the number of co-occurring diseases. While in one group costs increased with the number of co-occurring diseases, in a second group cost tended to decrease. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26989852 TI - Body mass index predicts discontinuation due to ineffectiveness and female sex predicts discontinuation due to side-effects in patients with psoriasis treated with adalimumab, etanercept or ustekinumab in daily practice: a prospective, comparative, long-term drug-survival study from the BioCAPTURE registry. AB - BACKGROUND: Predictors for successful treatment are important for personalized medicine. Predictors for drug survival of biologics in psoriasis have been assessed, but not split for different biologics or for the reason of discontinuation. OBJECTIVES: To compare long-term drug survival between the outpatient biologics adalimumab, etanercept and ustekinumab in patients with psoriasis, and to elucidate predictors for overall survival and drug discontinuation due to ineffectiveness and side-effects for each biologic separately. METHODS: Ten years of data were extracted from the prospective, multicentre, long-term BioCAPTURE registry. Kaplan-Meier survival analyses and confounder-corrected multivariate Cox regression analysis for drug survival (MCR DS) were performed to compare drug survival between biologics. To elucidate the predictors for different reasons of discontinuation for each biologic, univariate Cox regression analyses and multivariate Cox regression analyses for predictors (MCR-P) with backward selection were performed. RESULTS: In total, 526 treatment episodes - 186 adalimumab, 238 etanercept and 102 ustekinumab - were included covering 1333 treatment years. MCR-DS showed a significantly higher overall survival for ustekinumab compared with adalimumab and etanercept. MCR-P showed that higher body mass index (BMI) was a predictor for discontinuation due to ineffectiveness for etanercept and ustekinumab and that female sex was a predictor for discontinuation due to side-effects for adalimumab, etanercept and ustekinumab. CONCLUSIONS: Ustekinumab has the highest confounder-corrected long term drug survival in psoriasis treatment, compared with adalimumab and etanercept. Higher BMI is a predictor for discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side-effects in all three outpatient biologics. PMID- 26989853 TI - Patient-reported outcome and its association with attachment type and bone volume in mandibular implant overdenture. AB - OBJECTIVE: To determine oral health-related quality of life (OHRQoL) and denture satisfaction (DS) in patients provided with mandibular implant-supported overdentures (ISOD) retained by two different attachment types, and the association of mandibular bone volume with the change in patient-reported outcome, before and after implant treatment. MATERIAL AND METHODS: Thirty-four patients (mean age 60.70 +/- 8.7 years) received telescopic crown or locator attachments for ISOD and completed OHIP-14 (Malaysian version) and DS questionnaires, at baseline (T0 ) with new conventional complete dentures (CCD) and 3 months (T1 ) and 3 years (T2 ) after ISOD conversion. Mandibular bone volume was calculated from cone beam computed tomography (CBCT) datasets using Mimics software. Mean changes (MC) in OHIP-14 and DS at intervals were analyzed using the Wilcoxon signed-rank test and effect size (ES). The association of bone volume, implant attachment type, and other patient variables with the change in OHIP-14 and DS were determined using multivariate linear regression analysis. RESULTS: The MC in OHIP-14 and DS scores from T0 to T1 and T2 showed significant improvement with moderate and large ES, respectively. Regression analyses for the change in OHIP-14 score from T0 to T2 showed significant association with implant attachment type (P = 0.043), bone volume (P = 0.004), and baseline OHIP-14 (P = 0.001), while for DS, the association was only significant with baseline DS score (P = 0.001). CONCLUSION: Improvement in patients' OHRQoL and satisfaction with ISOD was associated with their baseline ratings. Mandibular bone volume had a stronger association for improvement in OHRQoL compared to type of attachment. PMID- 26989854 TI - Conducting pi Columns of Highly Symmetric Coronene, The Smallest Fragment of Graphene. AB - Coronene, which is the smallest D6h -symmetric polycyclic aromatic hydrocarbon, attracts particular attention as a basic component of electronic materials because it is the smallest fragment of graphene. However, carrier generation by physical methods, such as photo- or electric field-effect, has barely been studied, primarily because of the poor pi-conduction pathway in pristine coronene solid. In this work we have developed unprecedented pi-stacking columns of cationic coronene molecules by electrochemical hole-doping with polyoxometallate dianions. The face-to-face pi-pi interactions as well as the partially charged state lead to electrical conductivity at room temperature of up to 3 S cm(-1) , which is more than 10 orders of magnitude higher than that of pristine coronene solid. Additionally, the robust pi-pi interactions strongly suppress the in-plane rotation of the coronene molecules, which has allowed the first direct observation of the static Jahn-Teller distortion of cationic coronene molecules. PMID- 26989855 TI - High baseline bilirubin and low albumin predict liver decompensation and serious adverse events in HCV-infected patients treated with sofosbuvir-containing regimens. AB - To conduct surveillance and determine the safety profile of new hepatitis C virus treatments in real-world clinical practice. Hepatic decompensation and other serious adverse events were investigated in an observational cohort study of 511 patients treated with regimens containing sofosbuvir, December 2013-June 2014. Among 499 previously stable patients (no history of hepatic decompensation during the previous 12 months), a nested case-control study was performed to identify predictors of decompensation/serious adverse event. Cases and controls were matched 1:5 based on treatment regimen and duration. Matched conditional logistic regression was used for analysis. Providers scored the likelihood that events were treatment-related (scale = 0-4). The cumulative incidence of decompensation/events was 6.4% for the total cohort. Among 499 previously stable patients, the incidence of decompensation/events was 4.5%; the mortality rate was 0.6%. Sixteen of the 499 experienced one or more serious complications considered to be at least potentially treatment-related, and the sustained virological response rate was 7/16 (44%). Two cases, both on sofosbuvir/simeprevir (without interferon or ribavirin), had complications consistent with autoimmune events (score 3, 'likely treatment-related'), and one experienced a flare of autoimmune hepatitis. Compared to controls, cases had higher baseline median model for end stage liver disease scores (14 vs 8, P < 0.01). Decompensation/events was independently associated with lower baseline albumin (OR = 0.12/g/dL, P = 0.01) and higher total bilirubin (OR = 4.31/mg/dL, P = 0.01). Reduced hepatic function at baseline increased the risk of liver decompensation/events. PMID- 26989856 TI - When is bigger better? The effects of group size on the evolution of helping behaviours. AB - Understanding the evolution of sociality in humans and other species requires understanding how selection on social behaviour varies with group size. However, the effects of group size are frequently obscured in the theoretical literature, which often makes assumptions that are at odds with empirical findings. In particular, mechanisms are suggested as supporting large-scale cooperation when they would in fact rapidly become ineffective with increasing group size. Here we review the literature on the evolution of helping behaviours (cooperation and altruism), and frame it using a simple synthetic model that allows us to delineate how the three main components of the selection pressure on helping must vary with increasing group size. The first component is the marginal benefit of helping to group members, which determines both direct fitness benefits to the actor and indirect fitness benefits to recipients. While this is often assumed to be independent of group size, marginal benefits are in practice likely to be maximal at intermediate group sizes for many types of collective action problems, and will eventually become very small in large groups due to the law of decreasing marginal returns. The second component is the response of social partners on the past play of an actor, which underlies conditional behaviour under repeated social interactions. We argue that under realistic conditions on the transmission of information in a population, this response on past play decreases rapidly with increasing group size so that reciprocity alone (whether direct, indirect, or generalised) cannot sustain cooperation in very large groups. The final component is the relatedness between actor and recipient, which, according to the rules of inheritance, again decreases rapidly with increasing group size. These results explain why helping behaviours in very large social groups are limited to cases where the number of reproducing individuals is small, as in social insects, or where there are social institutions that can promote (possibly through sanctioning) large-scale cooperation, as in human societies. Finally, we discuss how individually devised institutions can foster the transition from small-scale to large-scale cooperative groups in human evolution. PMID- 26989857 TI - A validated LC-MS/MS method for the determination of canagliflozin, a sodium glucose co-transporter 2 (SGLT-2) inhibitor, in a lower volume of rat plasma: application to pharmacokinetic studies in rats. AB - Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of canagliflozin in a lower volume of rat plasma (0.1 mL) was established and applied to a pharmacokinetic study in rats. Following liquid-liquid extraction by tert-butyl methyl ether, chromatographic separation of canagliflozin was performed on a Quicksorb ODS (2.1 mm i.d. * 150 mm, 5 um size) using acetonitrile-0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.2 mL/min. The detection was carried out using an API 3200 triple-quadrupole mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z = 462.0 [M + NH4 ](+) -> 191.0 for canagliflozin and m/z = 451.2 [M + H](+) -> 71.0 for empagliflozin (internal standard) were obtained. The validation of the method was investigated, and it was found to be of sufficient specificity, accuracy and precision. Canagliflozin in rat plasma was stable under the analytical conditions used. This validated method was successfully applied to assess the pharmacokinetics of canagliflozin in rats using 0.1 mL rat plasma. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26989858 TI - New Frontiers for Conditional Release: Applying Lessons Learned from Other Offenders with Mental Illness. AB - There is relatively little research in the literature on insanity acquittees as compared with the large number of studies focused on the supervision and treatment of probationers and parolees with mental illness. Ideally, the latter literature could be successfully applied to insanity acquittees discharged from an inpatient hospital on "conditional release." This article describes the challenges faced by persons on conditional release as well as the gaps in extant conditional release literature. Then, five evidence-based models for the supervision and/or treatment of probationers and parolees with mental illness are applied to a theoretical conditionally released population (mental health courts, forensic assertive community treatment teams, the risk-need-responsivity model, informed supervision practices, and HOPE probation). Benefits and limitations are noted, and recommendations for such crossover are given. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26989859 TI - Evaluation of the Biological Activity of Opuntia ficus indica as a Tissue- and Estrogen Receptor Subtype-Selective Modulator. AB - Phytoestrogens are selective estrogen receptor modulators (SERMs) with potential for use in hormone replacement therapy (HRT) to relieve peri/postmenopausal symptoms. This study was aimed at elucidating the molecular mechanisms underlying the SERM properties of the extract of Korean-grown Opuntia ficus-indica (KOFI). The KOFI extract induced estrogen response element (ERE)-driven transcription in breast and endometrial cancer cell lines and the expression of endogenous estrogen-responsive genes in breast cancer cells. The flavonoid content of different KOFI preparations affected ERE-luciferase activities, implying that the flavonoid composition likely mediated the estrogenic activities in cells. Oral administration of KOFI decreased the weight gain and levels of both serum glucose and triglyceride in ovariectomized (OVX) rats. Finally, KOFI had an inhibitory effect on the 17beta-estradiol-induced proliferation of the endometrial epithelium in OVX rats. Our data demonstrate that KOFI exhibited SERM activity with no uterotrophic side effects. Therefore, KOFI alone or in combination with other botanical supplements, vitamins, or minerals may be an effective and safe alternative active ingredient to HRTs, for the management of postmenopausal symptoms. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26989860 TI - Effects of short-chain acyl-CoA dehydrogenase on cardiomyocyte apoptosis. AB - Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid beta oxidation, plays an important role in cardiac hypertrophy. However, its effect on the cardiomyocyte apoptosis remains unknown. We aimed to determine the role of SCAD in tert-butyl hydroperoxide (tBHP)-induced cardiomyocyte apoptosis. The mRNA and protein expression of SCAD were significantly down-regulated in the cardiomyocyte apoptosis model. Inhibition of SCAD with siRNA-1186 significantly decreased SCAD expression, enzyme activity and ATP content, but obviously increased the content of free fatty acids. Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP, such as the increase in cell apoptotic rate, the activation of caspase3 and the decrease in the Bcl-2/Bax ratio, which showed that SCAD may play an important role in primary cardiomyocyte apoptosis. The changes of phosphonate AMP-activated protein kinase alpha (p-AMPKalpha) and Peroxisome proliferator-activated receptor alpha (PPARalpha) in cardiomyocyte apoptosis were consistent with that of SCAD. Furthermore, PPARalpha activator fenofibrate and AMPKalpha activator AICAR treatment significantly increased the expression of SCAD and inhibited cardiomyocyte apoptosis. In conclusion, for the first time our findings directly demonstrated that SCAD may be as a new target to prevent cardiomyocyte apoptosis through the AMPK/PPARalpha/SCAD signal pathways. PMID- 26989861 TI - Acute-on-chronic liver failure in India: The Indian National Association for Study of the Liver consortium experience. AB - BACKGROUND AND AIM: The aim of this study was to analyze etiologies and frequency of hepatic and extrahepatic organ failures (OFs) and outcome of acute-on-chronic liver failure (ACLF) at 10 tertiary centers in India. METHODS: In this retrospective study (2011-2014), patients satisfying Asian Pacific Association for the Study of the Liver definition of ACLF were included. Etiology of acute precipitating insult and chronic liver disease and outcomes were assessed. Occurrence and severity of OF were assessed by chronic liver failure-sequential organ failure assessment score. RESULTS: The mean (+/-SD) age of 1049 consecutive ACLF patients was 44.7 +/- 12.2 years; Eighty-two percent were men. Etiology of acute precipitants included alcohol 35.7%, hepatitis viruses (hepatitis A, hepatitis B, and hepatitis E) 21.4%, sepsis 16.6%, variceal bleeding 8.4%, drugs 5.7%, and cryptogenic 9.9%. Among causes of chronic liver disease, alcohol was commonest 56.7%, followed by cryptogenic and hepatitis viruses. Predictors of survival were analyzed for a subset of 381 ACLF patients; OF's liver, renal, coagulation, cerebral, respiratory, and failure were seen in 68%, 32%, 31.5%, 22.6%, 14.5%, and 15%, respectively. Fifty-seven patients had no OF, whereas 1, 2, 3, 4, and 5 OFs were recorded in 126, 86, 72, 28, and 12 patients, respectively. The mortality increased progressively with increasing number of OFs (12.3% with no OF, 83.3% with five OFs). During a median hospital stay of 8 days, 42.6% (447/1049) of patients died. On multivariate analysis by Cox proportional hazard model, elevated serum creatinine (hazard ratio [HR] 1.176), advanced hepatic encephalopathy (HR 2.698), and requirement of ventilator support (HR 2.484) were independent predictors of mortality. CONCLUSIONS: Alcohol was the commonest etiology of ACLF. Within a mean hospital stay of 8 days, 42% patients died. OFs independently predicted survival. PMID- 26989862 TI - Increasing role of the cancer chemotherapeutic doxorubicin in cellular metabolism. AB - OBJECTIVES: The use of doxorubicin, a drug utilised for many years to treat a wide variety of cancers, has long been limited due to the significant toxicity that can occur not only during, but also years after treatment. It has multiple mechanisms of action including the intercalation of DNA, inhibition of topoisomerase II and the production of free radicals. We review the literature, with the aim of highlighting the role of drug concentration being an important determinant on the unfolding cell biological events that lead to cell stasis or death. METHODS: The PubMed database was consulted to compile this review. KEY FINDINGS: It has been found that the various mechanisms of action at the disposal of doxorubicin culminate in either cell death or cell growth arrest through various cell biological events, such as apoptosis, autophagy, senescence and necrosis. Which of these events is the eventual cause of cell death or growth arrest appears to vary depending on factors such as the patient, cell and cancer type, doxorubicin concentration and the duration of treatment. CONCLUSIONS: Further understanding of doxorubicin's influence on cell biological events could lead to an improvement in the drug's efficacy and reduce toxicity. PMID- 26989863 TI - Proteomic analysis of sheep primary testicular cells infected with bluetongue virus. AB - Bluetongue virus (BTV) causes a non-contagious, arthropod-transmitted disease in wild and domestic ruminants, such as sheep. In this study, we used iTRAQ labeling coupled with LC-MS/MS for quantitative identification of differentially expressed proteins in BTV-infected sheep testicular (ST) cells. Relative quantitative data were obtained for 4455 proteins in BTV- and mock-infected ST cells, among which 101 and 479 proteins were differentially expressed at 24 and 48 h post-infection, respectively, indicating further proteomic changes during the later stages of infection. Ten corresponding genes of differentially expressed proteins were validated via real-time RT-PCR. Expression levels of three representative proteins, eIF4a1, STAT1 and HSP27, were further confirmed via western blot analysis. Bioinformatics analysis disclosed that the differentially expressed proteins are primarily involved in biological processes related to innate immune response, signal transduction, nucleocytoplasmic transport, transcription and apoptosis. Several upregulated proteins were associated with the RIG-I-like receptor signaling pathway and endocytosis. To our knowledge, this study represents the first attempt to investigate proteome-wide dysregulation in BTV infected cells with the aid of quantitative proteomics. Our collective results not only enhance understanding of the host response to BTV infection but also highlight multiple potential targets for the development of antiviral agents. PMID- 26989864 TI - Changes in ductus venosus flow profile in twin-twin transfusion syndrome: role in risk stratification. AB - OBJECTIVES: To evaluate changes in ductus venosus (DV) waveforms and the timing of these changes in twin-twin transfusion syndrome (TTTS), to relate these to disease severity and to assess the clinical applicability of the suggested measurements in the prediction of TTTS. METHODS: DV time intervals and velocity time integrals (VTI) normalized to cardiac cycle and total VTI, respectively, as well as velocity ratios were analyzed in 149 monochorionic diamniotic (MCDA) twin pairs. Pregnancies were assigned to the following groups: uncomplicated MCDA (n = 29); TTTS Stages I+II (n = 50); TTTS Stages III+IV (n = 49); and pre-TTTS (n = 21), of which 14 remained stable and seven progressed to TTTS. Intertwin differences were calculated as larger/recipient minus smaller/donor and related to disease severity. Receiver-operating characteristics curve analysis was used to distinguish TTTS vs uncomplicated MCDA and pre-TTTS progressing to TTTS vs non progressing pre-TTTS. Intra- and interobserver reliability of measurement of DV parameters were evaluated using intraclass correlation coefficients (ICCs). RESULTS: No intertwin differences in DV parameters were found in uncomplicated MCDA pregnancies. Diastolic VTIs and filling times were significantly shorter in recipient twins in TTTS cases and in larger pre-TTTS twins in comparison with their cotwins. Time intervals, VTIs and velocity ratios correlated significantly with Quintero stages. An intertwin difference in early filling time (eT) normalized to cardiac cycle, eT (%) <= -3.6%, could differentiate TTTS from uncomplicated MCDA pregnancies (82.8% sensitivity; 79.8% specificity) and eT (%) <= -2.8% predicted progression to TTTS (73.1% sensitivity; 67.4% specificity). CONCLUSIONS: DV flow profiles and timing of waveform events are already altered in pre-TTTS and early-stage disease, reflecting abnormal ventricular filling and circulatory imbalance. Intertwin comparison of filling times and VTI may allow prediction of evolving TTTS in MCDA pregnancies. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26989865 TI - Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering. AB - Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-beta1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-beta1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-beta1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. PMID- 26989866 TI - Robot-assisted laparoscopic myomectomy for deep intramural myomas. AB - BACKGROUND: To evaluate the efficacy of robot-assisted laparoscopic myomectomy for deep intramural myomas. METHODS: We have conducted a retrospective study for 170 patients who underwent robot-assisted laparoscopic myomectomy by a single operator of tertiary university hospital. RESULTS: There were 100 cases of robot assisted laparoscopic myomectomy for deep intramural myomas. The patients had 3.8+/-3.5 myomas on average, and the mean size of the largest myoma of each patient was 7.5+/-2.1 centimeters in diameter. Mean operative time was 276.4+/ 97.1 minutes, and mean console time was 146.0+/-62.7 minutes. Thirty two patients had surgeries for other gynecologic conditions such as pelvic endometriosis or endometrial polyps along with myomectomy at the same time. All the patients recovered without any major complication. After the surgery, nine(75.0 %) of the 12 women pursuing a pregnancy became pregnant. CONCLUSION: Robot-assisted laparoscopic myomectomy for deep intramural myomas could be a minimal invasive surgical option for women who wish preserve fertility. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26989867 TI - Comparison between cytospin and liquid-based cytology in urine specimens classified according to the Paris System for Reporting Urinary Cytology. AB - BACKGROUND: The current study compared ThinPrep urinary cytology and conventional cytospin urinary cytology in the diagnosis of bladder cancer, applying the Paris System for Reporting Urinary Cytology. METHODS: Between January 2010 and December 2011, a total of 3659 urine samples were processed using conventional cytospin methods. Between January 2012 and December 2013, a total of 4186 urine cytological cases were analyzed using ThinPrep methods. In 131 cases (65 processed by conventional cytospin and 66 processed by ThinPrep), a subsequent biopsy was performed. The authors reclassified these cases according to the Paris System and an analysis between the 2 methods with regard to bladder biopsies was performed. RESULTS: No significant differences were observed in terms of sensitivity and specificity between the 2 methods in cases with positive cytology for high-grade carcinoma. According to the Paris System, cases of atypical urothelial cells (AUC) and atypical urothelial cells suspicious for high-grade carcinoma (AUC-H) that were processed using cytospin did not correlate with urothelial carcinoma or with negative biopsies; conversely, the AUC cases processed using ThinPrep appeared to correlate with negative histological biopsies or low-grade urothelial carcinoma. CONCLUSIONS: The results of the current study demonstrated that according to the Paris System, there were no significant differences in sensitivity or specificity for the diagnosis of high grade urothelial carcinoma or AUC-H between the 2 methods. Cases of AUC should be easy to recognize using Thin Prep rather than cytospin and only AUCs diagnosed with ThinPrep were found to be statistically linked to negative cases for carcinoma or with low-grade urothelial carcinoma. Cancer Cytopathol 2016;124:519 23. (c) 2016 American Cancer Society. PMID- 26989868 TI - Tunable fibre-coupled multiphoton microscopy with a negative curvature fibre. AB - Negative curvature fibre (NCF) guides light in its core by inhibiting the coupling of core and cladding modes. In this work, an NCF was designed and fabricated to transmit ultrashort optical pulses for multiphoton microscopy with low group velocity dispersion (GVD) at 800 nm. Its attenuation was measured to be <0.3 dB m(-1) over the range 600-850 nm and the GVD was -180 +/- 70 fs(2) m(-1) at 800 nm. Using an average fibre output power of ~20 mW and pulse repetition rate of 80 MHz, the NCF enabled pulses with a duration of <200 fs to be transmitted through a length of 1.5 m of fibre over a tuning range of 180 nm without the need for dispersion compensation. In a 4 m fibre, temporal and spectral pulse widths were maintained to within 10% of low power values up to the maximum fibre output power achievable with the laser system used of 278 mW at 700 nm, 808 mW at 800 nm and 420 mW at 860 nm. When coupled to a multiphoton microscope, it enabled imaging of ex vivo tissue using excitation wavelengths from 740 nm to 860 nm without any need for adjustments to the set-up. PMID- 26989869 TI - Ion currents in embryo development. AB - Ion channels are proteins expressed in the plasma membrane of electrogenic cells. In the zygote and blastomeres of the developing embryo, electrical modifications result from ion currents that flow through these channels. This phenomenon implies that ion current activity exerts a specific developmental function, and plays a crucial role in signal transduction and the control of embryogenesis, from the early cleavage stages and during growth and development of the embryo. This review describes the involvement of ion currents in early embryo development, from marine invertebrates to human, focusing on the occurrence, modulation, and dynamic role of ion fluxes taking place on the zygote and blastomere plasma membrane, and at the intercellular communication between embryo cell stages. PMID- 26989870 TI - Accuracy of EASI 12-lead ECGs in monitoring ST-segment and J-point by nurses in the Coronary Care Units. AB - AIMS AND OBJECTIVES: To confirm the accuracy of the EASI system compared to the standard 12-lead electrocardiogram, which is the gold standard, in monitoring the two major parameters used in the Coronary Care Units to detect myocardial ischaemia: ST-segment and J-point. BACKGROUND: Continuous electrocardiograph monitoring is used in the Coronary Care Units to detect cardiac conduction abnormalities and to show the morphology of electrocardiographic waves and tracts. Its accuracy is essential for efficient nursing vigilance, particularly for monitoring the ST segment and the J-point, in which alterations may indicate the onset of myocardial ischaemia. DESIGN: An observational study was conducted. METHODS: The enrolled patients (n = 253) simultaneously underwent standard electrocardiogram (10 electrodes) and EASI electrocardiogram (five electrodes). Data were collected by the Coronary Care Units nurses. Tests to compare differences in means and medians between the two sets of measurements were performed, and the Bland-Altman plots were used to illustrate their agreement. RESULTS: All 6.072 electrocardiographic leads (3.036 standard and 3.036 EASI) were recorded and analysed. Between the two measurement methods, very small statistically significant differences were found in some leads which are not clinically relevant for both the ST-segment or the J-point. CONCLUSIONS: This study confirms that the accuracy of the EASI 12-leadelectrocardiogram, compared to the standard 12-leadelectrocardiogram, which is the gold standard, is acceptable for clinical practice to monitor the two major parameters used in the Coronary Care Units for detecting myocardial ischaemia: ST-segment and J-point. RELEVANCE TO CLINICAL PRACTICE: The EASI system ensures: (1) ease of use and comfort for patients admitted to Coronary Care Units because it only requires five electrodes; (2) increased efficacy of nursing vigilance in the early detection of changes in ST-segment and J- point measurements. PMID- 26989871 TI - The impact of national guidelines on venom immunotherapy practice in the United Kingdom. PMID- 26989872 TI - Reply: Gleason and Fuhrman no longer make the grade. PMID- 26989873 TI - Relative maturity and the development of immunity to gastrointestinal nematodes in sheep: an overlooked paradigm? AB - Sheep display considerable variation in both the timing and magnitude of development of immunity to gastrointestinal nematodes (GIN). Onset of immunity is dependent on a number of factors, including antigenic stimulus, nutrition supply, age and size of the animals, the latter of which are confounded. Here, we review the factors associated with the development of immunity to GIN in sheep, particularly in the context of the role that relative maturity may have through applying the rules of genetic size scaling based on examples from published literature. Comparing animals based on their metabolic age, rather than chronological age, may provide an explanation for the timing of immune development and may reduce the variation in immune development that frequently is observed both between and within breeds. Further, this approach may help explain the phenotypic differences in animal performance between animals of varying immunological capacity to GIN through influences on mature body weight. As such, when considering factors influencing immune development to GIN, physiological age or relative maturity may be considered an overlooked paradigm. We propose it may be worthwhile to consider metabolic age when comparing the immune competence of animals to ensure the subjects are at an analogous stage of physiological development. PMID- 26989874 TI - MicroRNA-195a-3p inhibits angiogenesis by targeting Mmp2 in murine mesenchymal stem cells. AB - MicroRNAs (miRNAs) modulate complex physiological and pathological processes, including the regulation of angiogenesis. Our previous study reported that bone marrow-derived mesenchymal stem cells (MSCs) are recruited into choroidal neovascularization lesions. miRNA-195 is highly expressed in MSCs, but its function remains unknown. In the present study, miR-195a-3p abundance was significantly decreased in hypoxia-treated murine MSCs; on the other hand, its overexpression reduced MSC proliferation and migration while increasing the activation of anti-angiogenic factor pigment epithelium-derived factor (PEDF). We further discovered that matrix metalloproteinase 2 (Mmp2) transcript is a target of miR-195a-3p, and that silencing Mmp2 phenocopied the reduced proliferation and migration of MSCs. The therapeutic potential of miR-195a-3p as an angiogenesis inhibitor was also demonstrated in a laser-induced choroidal neovascularization mouse model. These findings collectively indicate that miR-195a-3p is a negative modulator of angiogenesis, and could be used as an angiogenesis inhibitor. Mol. Reprod. Dev. 83: 413-423, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26989876 TI - School breakfast and body mass index: a longitudinal observational study of middle school students. AB - OBJECTIVES: The objectives are to identify breakfast location patterns (frequency and place of breakfast consumption) and explore the association between breakfast patterns and weight status over time among preadolescents. METHODS: Surveys and physical measurements were completed among students from 12 randomly selected schools in a medium-sized urban school district. All students were followed from fifth (Fall, 2011) to seventh grade (Fall, 2013). Latent transition analysis and longitudinal analyses were used in the study. RESULTS: Six distinct breakfast location patterns emerged at baseline (1) frequent skippers; (2) inconsistent school eaters; (3) inconsistent home eaters; (4) regular home eaters; (5) regular school eaters and (6) double breakfast eaters. Results from the longitudinal analyses revealed that there was an increased odds of overweight/obesity among frequent skippers compared with double breakfast eaters after adjusting for school, year and students' race/ethnicity (AOR: 2.66, 95% CI: 1.67, 4.24). Weight changes from year to year were similar between double breakfast eaters and other students. CONCLUSIONS: Concerns that a second breakfast at school increases risk of excessive weight gain are unsupported. Students who regularly consumed breakfasts at school, including double breakfast eaters, were more likely to exhibit a healthy weight trajectory. Additional research is needed to understand the impact of universal school breakfast on students' overall diets. PMID- 26989875 TI - Punicalagin attenuates palmitate-induced lipotoxicity in HepG2 cells by activating the Keap1-Nrf2 antioxidant defense system. AB - SCOPE: Free fatty acids (FFA) could induce hepatocyte lipotoxicity, which plays an important role in the initiation of nonalcoholic fatty liver disease (NAFLD). Inhibition of FFA-induced lipotoxicity is suggested as a potential treatment for nonalcoholic fatty liver disease. The aim of the current study is to explore the effect of punicalagin, a polyphenol abundant in pomegranate, on FFA-induced hepatic lipotoxicity and its potential mechanisms. METHODS AND RESULTS: HepG2 cells were exposed to 250 MUM palmitate for 24 h with or without punicalagin pretreatment. Punicalagin pretreatment attenuated palmitate-induced mitochondrial membrane potential lost, ATP depletion, and reactive oxygen species production. Punicalagin also increased hepatocyte viability by blocking mitochondria-mediated caspase-dependent apoptosis. The hepatoprotective effect was associated with an exaggerated phosphorylation of extracellular signal regulated kinase as well as significant nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and target genes induction. Blockage of extracellular signal regulated kinase by a pharmacological inhibitor abrogated the cytoprotective effect of punicalagin and its induction of Nrf2 pathway. Knockdown of Nrf2 by specific small interfering RNA also diminished the protective effects of punicalagin, while knockdown of Kelch-like ECH-associated protein 1 (Keap1) with small interfering RNA could promote Nrf2 nuclear translocation and exert similar protection as punicalagin treatment. CONCLUSIONS: These findings suggest that punicalagin could effectively attenuate FFA-induced lipotoxicity by activating Keap1-Nrf2 cytoprotective signaling pathway. PMID- 26989877 TI - Clinical impact of a high-sensitivity troponin assay introduction on patients presenting to the emergency department. AB - OBJECTIVE: Biomarkers are a critical component in the investigation of patients with potential ischaemic heart disease. The proposed benefits of a high sensitivity troponin (hs-Tn) assay include earlier diagnosis of myocardial infarction. However, the decreased specificity may adversely affect clinical practice. The present study aims to investigate the impact that the introduction of a hs-Tn assay had on patients presenting to the ED. METHODS: A pre- and post interventional analysis was performed on all patients presenting to the Royal Melbourne Hospital ED, and had a troponin, in the 12 months before and after the introduction of the hs-Tn assay. The main outcome measures were ED length of stay, admission rates, proportion of patients undergoing interventional cardiac procedures and proportion diagnosed with myocardial infarction. RESULTS: There were 6557 patients who had a conventional assay and 7335 patients who had a hs-Tn assay. The introduction of a hs-Tn assay was associated with an increased abnormal troponin rate (23.4% vs 28.1%, P < 0.001). The median length of ED stay decreased by 9.1% (P < 0.001). The proportion admitted to hospital increased (60.9% vs 65.9%, P < 0.001); however, there was no difference in the proportion undergoing revascularisation or the proportion diagnosed with myocardial infarction. CONCLUSIONS: Although the introduction of a hs-Tn assay led to an increase in hospital admissions, the unchanged rate of cardiac procedures or final diagnoses of acute myocardial infarction and ischaemic heart disease suggests that the hs-Tn did not improve the detection of these conditions. It remains unclear whether there was a benefit admitting the additional cohort of patients. PMID- 26989878 TI - Narrative abilities of monolingual and bilingual children with and without language impairment: implications for clinical practice. AB - BACKGROUND: Understanding and expressing a narrative's macro-structure is relatively independent of experience in a specific language. A narrative task is therefore assumed to be a less biased method of language assessment for bilingual children than many other norm-referenced tests and may thus be particularly valuable to identify language impairment (LI) in a bilingual context. AIMS: The present study aimed to investigate the effects of LI and bilingualism on macrostructural narrative skills. Moreover, it evaluated the diagnostic validity of a narrative task within a monolingual and bilingual sample. METHODS & PROCEDURES: Five- and 6-year-old mono- and bilingual children with and without LI (N = 33 per group) were tested on production and comprehension measures of narrative macro-structure. A multivariate analysis of covariance (MANCOVA) was used to investigate the effects of LI and bilingualism on their narrative abilities. Binary logistic regressions were conducted to evaluate the instrument's diagnostic value. OUTCOMES & RESULTS: Negative effects of LI were found on all narrative measures, whereas no effects of bilingualism emerged. The narrative task adequately differentiated between both mono- and bilingual children with and without LI, with story elements related to internal states being more effective than elements related to the basic episode structure. CONCLUSIONS & IMPLICATIONS: This study confirms the hypothesis that measures of narrative macro-structure are not biased against children who have less experience with a particular language, like bilinguals. In addition, it indicates that using narratives to assess children's language abilities can support the identification of LI in both a monolingual and a bilingual context. PMID- 26989879 TI - Molecular screening of CFTR gene in Egyptian patients with congenital bilateral absence of the vas deferens: a preliminary study. AB - In the current study, we enrolled 14 Egyptian infertile males with isolated congenital bilateral absence of the vas deferens (CBAVD). Screening for the most commonly reported 36 CFTR mutations, and the intron 8 (T)n splice variant was performed by multiplex PCR followed by reversed hybridisation. Samples with the 5T variant were picked for DNA sequencing of intron 8/exon 9 region to identify the number of adjacent TG repeats. The p.Phe508del and the p.Ser1251Asn mutations were detected in heterozygous state in three patients (10.7% of alleles) and in one patient (3.6% of alleles), respectively, while the 5T variant was detected in five patients (28.6% of alleles). Among those five patients, four had TG12 repeats and one had TG13 repeats confirming the pathogenic penetrance of all 5T alleles in Egyptian CBAVD patients. The allelic frequencies of the mutations p.Phe508del, p.Ser1251Asn and the 5T variant in 60 Egyptian cystic fibrosis patients were 24.2%, 3.3% and 2.5% respectively. The mutation p.Ser1251Asn was detected for the first time in isolated CBAVD patient in our study. Due to the high prevalence of p.Phe508del mutation and 5T variant in Egyptian CBAVD patients, we recommend their screening initially, ideally followed by full CFTR gene sequencing in unidentified patients. PMID- 26989880 TI - Interleukin-9 and interleukin-17C in chronic rhinosinusitis. AB - BACKGROUND: Interleukin (IL)-9 and IL-17C have been known to play a role in allergic inflammation, yet, their roles in chronic rhinosinusitis (CRS) are not well defined. IL-9 induces changes in epithelial cell gene expression leading to goblet cell metaplasia, whereas IL-17C is functionally distinct in that its expression can be induced by bacterial challenge and inflammatory stimuli. This study aimed to compare levels of IL-9 and IL-17C in CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) as well as atopy. METHODS: Nasal polyp or sinus mucosal specimens from CRSwNP (n = 36), CRSsNP (n = 9), and control (n = 9) groups were collected and processed. Patient atopy status was determined by history of skin-prick test and pulmonary function test. Immunohistochemistry was carried out using anti-human IL-9 and IL-17C antibodies. Positively-stained cells were enumerated under high-power (*400) magnification in 5 consecutive fields. RESULTS: The level of expression of IL-9 was higher in CRSwNP than CRSsNP and control. Similar findings were demonstrated in IL-17C with higher expression in CRSwNP than CRSsNP and control. Both the averages of positively-stained cells expressing IL-9 and IL-17C were higher in CRS with asthma and allergy compared to control. This suggested that IL-9 and IL-17C were both involved in the pathogenesis of CRS, allergy, and asthma. CONCLUSION: Inflammatory cell expression of IL-9 and IL-17C were increased in CRS, particularly with allergy and asthma. These interleukins may contribute to the pathogenesis of CRSwNP as well as atopy and may serve as therapeutic targets for disease management. PMID- 26989881 TI - Contemporary genetic structure and postglacial demographic history of the black scorpionfish, Scorpaena porcus, in the Mediterranean and the Black Seas. AB - Understanding the distribution of genetic diversity in the light of past demographic events linked with climatic shifts will help to forecast evolutionary trajectories of ecosystems within the current context of climate change. In this study, mitochondrial sequences and microsatellite loci were analysed using traditional population genetic approaches together with Bayesian dating and the more recent approximate Bayesian computation scenario testing. The genetic structure and demographic history of a commercial fish, the black scorpionfish, Scorpaena porcus, was investigated throughout the Mediterranean and Black Seas. The results suggest that the species recently underwent population expansions, in both seas, likely concomitant with the warming period following the Last Glacial Maximum, 20 000 years ago. A weak contemporaneous genetic differentiation was identified between the Black Sea and the Mediterranean Sea. However, the genetic diversity was similar for populations of the two seas, suggesting a high number of colonizers entered the Black Sea during the interglacial period and/or the presence of a refugial population in the Black Sea during the glacial period. Finally, within seas, an east/west genetic differentiation in the Adriatic seems to prevail, whereas the Black Sea does not show any structured spatial genetic pattern of its population. Overall, these results suggest that the Black Sea is not that isolated from the Mediterranean, and both seas revealed similar evolutionary patterns related to climate change and changes in sea level. PMID- 26989882 TI - Transition-Metal Carbodiimides as Molecular Negative Electrode Materials for Lithium- and Sodium-Ion Batteries with Excellent Cycling Properties. AB - We report evidence for the electrochemical activity of transition-metal carbodiimides versus lithium and sodium. In particular, iron carbodiimide, FeNCN, can be efficiently used as negative electrode material for alkali-metal-ion batteries, similar to its oxide analogue FeO. Based on (57)Fe Mossbauer and infrared spectroscopy (IR) data, the electrochemical reaction mechanism can be explained by the reversible transformation of the Fe-NCN into Li/Na-NCN bonds during discharge and charge. These new electrode materials exhibit higher capacity compared to well-established negative electrode references such as graphite or hard carbon. Contrary to its oxide analogue, iron carbodiimide does not require heavy treatments (such as nanoscale tailoring, sophisticated textures, or coating) to obtain long cycle life with current density as high as 9 A g(-1) for hundreds of charge-discharge cycles. Similar to the iron compound, several other transition-metal carbodiimides M(x)(NCN)y with M=Mn, Cr, Zn can cycle successfully versus lithium and sodium. Their electrochemical activity and performance open the way to the design of a novel family of anode materials. PMID- 26989883 TI - Hydrogen Bonding between Metal-Ion Complexes and Noncoordinated Water: Electrostatic Potentials and Interaction Energies. AB - The hydrogen bonding of noncoordinated water molecules to each other and to water molecules that are coordinated to metal-ion complexes has been investigated by means of a search of the Cambridge Structural Database (CSD) and through quantum chemical calculations. Tetrahedral and octahedral complexes that were both charged and neutral were studied. A general conclusion is that hydrogen bonds between noncoordinated water and coordinated water are much stronger than those between noncoordinated waters, whereas hydrogen bonds of water molecule in tetrahedral complexes are stronger than in octahedral complexes. We examined the possibility of correlating the computed interaction energies with the most positive electrostatic potentials on the interacting hydrogen atoms prior to interaction and obtained very good correlation. This study illustrates the fact that electrostatic potentials computed for ground-state molecules, prior to interaction, can provide considerable insight into the interactions. PMID- 26989884 TI - Oblique facial clefts in Johanson-Blizzard syndrome. AB - Johanson-Blizzard syndrome (JBS) is considered as an infrequent, but clinically easily recognizable autosomal recessive entity by the pathognomonic combination of congenital exocrine pancreatic insufficiency and hypoplastic alae nasi, in addition to other distinctive findings such as scalp defects, hypothyroidism, and rectourogenital malformations. There are few reports of patients with JBS in association with facial clefting, referring all to types 2 to 6 of Tessier's classification that can be characterized properly as oblique facial clefts (OFCs). We describe the clinical aspects in four patients with JBS and extensive OFCs. In all of them, the diagnosis of JBS was confirmed by the demonstration of homozygous or compound-heterozygous mutations in the UBR1 gene. Additionally, we review three previously reported cases of JBS with OFCs. Taking into account a number of approximately 100 individuals affected by JBS that have been published in the literature we estimate that the frequency of OFCs in JBS is between 5% and 10%. This report emphasizes that extensive OFCs may be the severe end of the spectrum of facial malformations occurring in JBS. No obvious genotype phenotype correlation could be identified within this cohort. Thus, UBR1 should be included within the list of contributory genes of OFCs, although the exact mechanism remains unknown. (c) 2016 Wiley Periodicals, Inc. PMID- 26989885 TI - Children post liver transplantation hospitalized with fever are at a high risk for bacterial infections. AB - BACKGROUND: Although infections post liver transplantation are a main cause of morbidity and mortality, data are limited on transplanted children. The objective of this study was to investigate the incidence, etiology, and predictors of infection in pediatric liver transplant recipients (LTR) in the specific practical clinical setting of hospitalization for fever in order to elucidate the appropriate management of these patients. METHODS: Clinical and laboratory data were retrospectively collected for all febrile pediatric LTR hospitalized from 2004 to 2012. RESULTS: We analyzed 133 hospital admissions for fever among 44 pediatric LTR. Of these, 73 bacterial (54.8%) and 46 viral infections (34.5%) were diagnosed. No cases of protozoa or fungal infections were reported. Bacterial infections were most frequent during the first year post transplantation with ascending cholangitis being the most prevalent. Twenty-six (36%) bacterial infections were microbiologically documented and 47 (64%) were clinically documented. Of the microbiologically confirmed cases, gram-negative bacteria, namely Enterobacteriaceae, were most common (57.7%). Seven cases of bacteremia were observed including 1 case presenting with severe sepsis. Compared with the white blood cell count and absolute neutrophil count, C-reactive protein level was found to be a more sensitive biomarker for bacterial disease. Older age on admission was a significant risk factor for bacterial infection. CONCLUSION: Febrile hospitalized pediatric LTR are immunocompromised hosts at high risk for bacterial infections, and usually warrant prompt evaluation and empirical antibiotic treatment upon admission. PMID- 26989886 TI - Kinetically Controlled Sequential Growth of Surface-Grafted Chiral Supramolecular Copolymers. AB - We report a facile strategy to grow supramolecular copolymers on Au surfaces by successively exposing a surface-anchored monomer to solutions of oppositely charged peptide comonomers. Charge regulation on the active chain end of the polymer sufficiently slows down the kinetics of the self-assembly process to produce kinetically trapped copolymers at near-neutral pH. We thereby achieve architectural control at three levels: The beta-sheet sequences direct the polymerization away from the surface, the height of the supramolecular copolymer brushes is well-controlled by the stepwise nature of the alternating copolymer growth, and 2D spatial resolution is realized by using micropatterned initiating monomers. The programmable nature of the resulting architectures renders this concept attractive for the development of customized biomaterials or chiral interfaces for optoelectronics and sensor applications. PMID- 26989887 TI - Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy. AB - Cancer immunotherapy using tumor-specific monoclonal antibodies presents a novel approach for cancer treatment. A monoclonal antibody TA99 specific for gp75 antigen of melanoma initiates neutrophil recruitment in tumor responsible for cancer therapy. Here, a strategy is reported for hijacking neutrophils in vivo using nanoparticles (NPs) to deliver therapeutics into tumor. In a mouse model of melanoma, it is shown that systemically delivered albumin NPs increase in tumor when TA99 antibody is injected; and the NP tumor accumulation is mediated by neutrophils. After the administration of pyropheophorbide-a loaded albumin NPs and TA99, photodynamic therapy significantly suppresses the tumor growth and increases mouse survival compared with treatment with the NPs or TA99. The study reveals a new avenue to treat cancer by NP hitchhiking of immune systems to enhance delivery of therapeutics into tumor sites. PMID- 26989889 TI - Endoscopic capsule retention: a complication with an underappreciated cause. PMID- 26989888 TI - Polyethylene glycol loxenatide injections added to metformin effectively improve glycemic control and exhibit favorable safety in type 2 diabetic patients. AB - BACKGROUND: The aim of the present study was to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) injections in Chinese type 2 diabetic (T2D) patients. METHODS: The present multicenter randomized double-blind parallel placebo-controlled clinical trial enrolled patients who had been treated with a stable dose of metformin (>=1500 mg/day) for >=12 weeks and had an HbA1c level between 7% and 11%. Subjects were randomly divided into three groups (1: 1: 1) and were treated with once weekly subcutaneous injections of either placebo or 100 or 200 MUg PEX168 for 12 weeks. All subjects continued to receive metformin daily. RESULTS: After 12 weeks treatment, the adjusted least-squares mean of HbA1c reductions from baseline values in the 100 and 200 MUg PEX168 groups were significantly higher than in the placebo group (-1.02% [95% confidence interval {CI} -1.33, -0.71), -1.36% [95% CI -1.68, -1.04], and 0.13% [95% CI -0.20, 0.45], respectively; P < 0.05). After treatment, 50% and 60.5% of subjects in the 100 and 200 MUg PEX168 groups, respectively, achieved HbA1c levels <7% (P < 0.01 for both vs placebo [HbA1c 11.1%]). The most frequent adverse reactions in the PEX168 groups were mild to moderate dose-dependent gastrointestinal reactions. There were no reports of hypoglycemia or pancreatitis in any of the groups. CONCLUSIONS: Continuous 12 week treatment with PEX168 showed excellent safety and efficacy in T2D patients whose glucose was not well controlled with metformin alone. PMID- 26989891 TI - Transfemoral temporary aortic balloon occlusion in surgical treatment of second trimester intramural ectopic pregnancy. AB - Intramural ectopic pregnancy is a rare type of ectopic pregnancy that may lead to life-threatening hemorrhage. In the present case, a 20-year-old woman at 18.5 weeks of gestation, G1 P0 , was diagnosed with intramural ectopic pregnancy on ultrasound and magnetic resonance imaging, which showed a 14-cm * 14-cm gestational sac on the right posterior lateral side of the uterus fundus, surrounded completely by myometrium. Considering the increased risk of bleeding during surgery, transfemoral temporary aortic balloon occlusion was performed during laparotomy. The intramural ectopic gestational sac was successfully resected without life-threatening obstetric hemorrhage. This procedure could offer an alternative approach to classic uterine artery embolization in reducing intraoperative bleeding thus avoiding blood transfusion. Aortic balloon occlusion is the temporary occlusion of the aorta, therefore it does not influence future fertility. In conclusion, transfemoral temporary aortic balloon occlusion is an effective procedure in the surgical treatment of intramural ectopic pregnancy diagnosed beyond the first trimester. PMID- 26989893 TI - Salvage hormonal therapy after failed microdissection testicular sperm extraction: A multi-institutional prospective study. AB - OBJECTIVE: To validate the efficacy of salvage hormonal therapy in men with non obstructive azoospermia at their second microdissection testicular sperm extraction. METHODS: This was a multi-institutional study registered at the Japanese University Hospital Medical Information Network clinical trial center. After 1 month of human chorionic gonadotropin therapy (5000 IU, three times a week), patients were treated with recombinant human follicle-stimulating hormone (150 IU, three times a week) and human chorionic gonadotropin for the next 3 months. Three testicular samples were obtained randomly from both testes, and sent for pathological diagnosis at the first and second microdissection testicular sperm extraction. RESULTS: A total of 21 men, excluding those with chromosomal abnormalities, azoospermia factor a or b deletions, extremely small testes (<2 mL), or prior hormonal therapy, were eligible to participate based on our inclusion criteria. At the first microdissection testicular sperm extraction, 13 and six patients had Sertoli cells only and an early maturation arrest, respectively. With the second microdissection testicular sperm extraction, sperm were successfully obtained from two patients (10%). Patient age, testicular volume and hormone profiles were not associated with the results of the second microdissection testicular sperm extraction. However, the testicular histology of the two successful patients were late maturation arrest and hypospermatogenesis. CONCLUSIONS: Effectiveness of human chorionic gonadotropin-based salvage hormonal therapy preceding a second microdissection testicular sperm extraction seems to be limited. Non-obstructive azoospermia men who have differentiated cells in their testes are likely to respond to hormonal stimulation. PMID- 26989894 TI - Establishing Clinically Relevant Severity Levels for the Central Sensitization Inventory. AB - OBJECTIVES: The aim of this study was to create and validate severity levels for the central sensitization inventory (CSI), a valid and reliable patient-reported outcome instrument designed to identify patients whose presenting symptoms may be related to a central sensitivity syndrome (CSS; eg, fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome), with a proposed common etiology of central sensitization (CS). METHODS: Based on CSI score means and standard deviations from previously published subject samples, the following CSI severity levels were established: subclinical = 0 to 29; mild = 30 to 39; moderate = 40 to 49; severe = 50 to 59; and extreme = 60 to 100. The concurrent validity of the CSI severity levels was then confirmed in a separate chronic pain patient sample (58% with a CSS diagnosis and 42% without) by demonstrating associations between CSI scores and (1) the number of physician-diagnosed CSSs; (2) CSI score distributions in both CSS and non-CSS patient samples; (3) patient-reported history of CSSs; and (4) patient-reported psychosocial measures, which are known to be associated with CSSs. RESULTS: Compared to the non-CSS patient subsample, the score distribution of the CSS patient subsample was skewed toward the higher severity ranges. CSI mean scores moved into higher severity levels as the number of individual CSS diagnoses increased. Patients who scored in the extreme CSI severity level were more likely to report previous diagnoses of fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, tension/migraine headaches, and anxiety or panic attacks (P < 0.01). CSI severity levels were also associated with patient-reported depressive symptoms, perceived disability, sleep disturbance, and pain intensity (P <= 0.02). CONCLUSION: This study provides support for these CSI severity levels as a guideline for healthcare providers and researchers in interpreting CSI scores and evaluating treatment responsiveness. PMID- 26989892 TI - A Randomized, Double-Blind, Active- and Placebo-Controlled Efficacy and Safety Study of Arhalofenate for Reducing Flare in Patients With Gout. AB - OBJECTIVE: Arhalofenate is a novel antiinflammatory uricosuric agent. The objective of this study was to evaluate its antiflare activity in patients with gout. METHODS: This was a 12-week, randomized, double-blind, controlled phase IIb study. Eligible patients had had >=3 flares of gout during the previous year, had discontinued urate-lowering therapy and colchicine, and had a serum uric acid (UA) level of 7.5-12 mg/dl. Patients were randomly assigned at a 2:2:2:2:1 ratio to receive 600 mg arhalofenate, 800 mg arhalofenate, 300 mg allopurinol, 300 mg allopurinol plus 0.6 mg colchicine, or placebo once a day. The primary outcome measure was the flare incidence (number of flares divided by time of exposure). The serum UA level was a secondary outcome measure. RESULTS: A total of 239 gout patients were randomized and took at least 1 dose of study medication. The primary outcome measure comparing flare incidence between 800 mg arhalofenate and 300 mg allopurinol was achieved, with a 46% decrease in the 800 mg arhalofenate group (0.66 versus 1.24; P = 0.0056). Treatment with 800 mg arhalofenate was also significantly better than placebo (P = 0.049) and not significantly different from treatment with 300 mg allopurinol plus 0.6 mg colchicine (P = 0.091). Mean changes in serum UA level were -12.5% with 600 mg arhalofenate and -16.5% with 800 mg arhalofenate (P = 0.001 and P = 0.0001, respectively, versus -0.9% with placebo). There were no meaningful differences in adverse events (AEs) between groups, and there were no serious AEs related to arhalofenate. Urinary calculus occurred in 1 patient receiving 300 mg allopurinol. No abnormal serum creatinine values >1.5-fold the baseline value were observed in the arhalofenate-treated groups. CONCLUSION: Arhalofenate at a dosage of 800 mg decreased gout flares significantly compared to allopurinol at a dosage of 300 mg. Arhalofenate was well tolerated and appeared safe. Arhalofenate is the first urate-lowering antiflare therapy. PMID- 26989895 TI - Collagen Matrix Remodeling in Stented Pulmonary Arteries after Transapical Heart Valve Replacement. AB - The use of valved stents for minimally invasive replacement of semilunar heart valves is expected to change the extracellular matrix and mechanical function of the native artery and may thus impair long-term functionality of the implant. Here we investigate the impact of the stent on matrix remodeling of the pulmonary artery in a sheep model, focusing on matrix composition and collagen (re)orientation of the host tissue. Ovine native pulmonary arteries were harvested 8 (n = 2), 16 (n = 4) and 24 (n = 2) weeks after transapical implantation of self-expandable stented heart valves. Second harmonic generation (SHG) microscopy was used to assess the collagen (re)orientation of fresh tissue samples. The collagen and elastin content was quantified using biochemical assays. SHG microscopy revealed regional differences in collagen organization in all explants. In the adventitial layer of the arterial wall far distal to the stent (considered as the control tissue), we observed wavy collagen fibers oriented in the circumferential direction. These circumferential fibers were more straightened in the adventitial layer located behind the stent. On the luminal side of the wall behind the stent, collagen fibers were aligned along the stent struts and randomly oriented between the struts. Immediately distal to the stent, however, fibers on both the luminal and the adventitial side of the wall were oriented in the axial direction, demonstrating the stent impact on the collagen structure of surrounding arterial tissues. Collagen orientation patterns did not change with implantation time, and biochemical analyses showed no changes in the trend of collagen and elastin content with implantation time or location of the vascular wall. We hypothesize that the collagen fibers on the adventitial side of the arterial wall and behind the stent straighten in response to the arterial stretch caused by oversizing of the stent. However, the collagen organization on the luminal side suggests that stent-induced remodeling is dominated by contact guidance. PMID- 26989896 TI - MicroRNA miR-371a-3p - A Novel Serum Biomarker of Testicular Germ Cell Tumors: Evidence for Specificity from Measurements in Testicular Vein Blood and in Neoplastic Hydrocele Fluid. AB - BACKGROUND: microRNAs (miRs)-371-3 are suggested to be novel biomarkers of germ cell tumors (GCTs), but their specificity is unresolved. We aimed at clarifying the origin of miR 371a-3p by measuring this miR in peripheral vein blood, and in fluids present in the vicinity of GCTs. METHODS: miR-371a-3p levels were measured by quantitative PCR in 9 tumor surrounding hydroceles and in cubital vein blood (CVB) and testicular vein blood (TVB) of 64 GCT patients, 51 with clinical stage (CS) 1, 13 with CS2-3. Thirty three CS1 cases had also postoperative CVB measurement. TVB miR levels were compared with those of CVB. Associations with clinical factors were analyzed statistically. RESULTS: TVB miR levels were 294 fold, 80-fold and 4.6-fold higher than those in CVB of CS1 patients, CS2-3 patients and controls, respectively. Neoplastic hydrocele fluid comprised of very high miR levels. In CS1, miR levels dropped to normal postoperatively. Statistically, CVB miR levels are significantly associated with tumor size (p = 0.0211) and testis length (p = 0.0493). TVB miR levels are associated with testis length (p = 0.0129). CONCLUSIONS: This study provides evidence for the origin of circulating miR 371a-3p molecules from GCT cells. miR-371a-3p represents a specific serum biomarker for germ cell cancer. PMID- 26989897 TI - Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering. AB - Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration-culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch. PMID- 26989898 TI - Promoting Healthy Behaviors among Egyptian Mothers: A Quasi-Experimental Study of a Health Communication Package Delivered by Community Organizations. AB - Decisions made at the household level, for example, to seek antenatal care or breastfeed, can have a direct impact on the health of mothers and newborns. The SMART Community-based Initiatives program in Egypt worked with community development associations to encourage better household decision-making by training community health workers to disseminate information and encourage healthy practices during home visits, group sessions, and community activities with pregnant women, mothers of young children, and their families. A quasi experimental design was used to evaluate the program, with household surveys conducted before and after the intervention in intervention and comparison areas. Survey questions asked about women's knowledge and behaviors related to maternal and newborn care and child nutrition and, at the endline, exposure to SMART activities. Exposure to program activities was high in intervention areas of Upper Egypt: 91% of respondents reported receiving home visits and 84% attended group sessions. In Lower Egypt, these figures were 58% and 48%, respectively. Knowledge of danger signs related to pregnancy, delivery, and newborn illness increased significantly more in intervention than comparison areas in both regions (with one exception in Lower Egypt), after controlling for child's age and woman's education; this pattern also occurred for two of five behaviors (antenatal care visits and consumption of iron-folate tablets). Findings suggest that there may have been a significant dose-response relationship between exposure to SMART activities and certain knowledge and behavioral indicators, especially in Upper Egypt. The findings demonstrate the ability of civil society organizations with minimal health programming experience to increase knowledge and promote healthy behaviors among pregnant women and new mothers. The SMART approach offers a promising strategy to fill gaps in health education and counseling and strengthen community support for behavior change. PMID- 26989899 TI - The Influence of Phacoemulsification on Surgical Outcomes of Trabeculectomy with Mitomycin-C for Uveitic Glaucoma. AB - PURPOSE: To evaluate the influence of phacoemulsification after trabeculectomy on the postoperative intraocular pressure (IOP) in eyes with uveitic glaucoma (UG). SETTING: Kumamoto University Hospital, Kumamoto, Japan. DESIGN: A retrospective cohort study. METHODS: The medical records of patients with UG who had trabeculectomy with mitomycin-C (MMC) were reviewed. Complete and qualified surgical failures were defined by an IOP of >=21 mmHg (condition A), >=18 mmHg (condition B), or >=15 mmHg (condition C) without and with glaucoma eye drops, respectively. Kaplan-Meier survival analysis, generalized by the Wilcoxon test, and the Cox proportional hazards model analysis were conducted. Post trabeculectomy phacoemulsification was treated as a time-dependent variable. In 24 (30%) of the included 80 eyes, phacoemulsification was included, and they were divided into two groups: groups I (8 eyes with phacoemulsification within 1 year after trabeculectomy) and group II (16 eyes after 1 year following trabeculectomy). RESULTS: Multivariable Cox proportional hazards model analysis showed post-trabeculectomy phacoemulsification was a significant factor in both complete success and qualified success based upon condition C (P = 0.0432 and P = 0.0488, respectively), but not for the other conditions. Kaplan-Meier survival analyses indicated significant differences in success probabilities between groups I and group II for complete success and qualified success based upon condition C (P = 0.020 and P = 0.013, respectively). There was also a significant difference for qualified success based upon condition B (P = 0.034), while there was no significant difference for the other conditions. CONCLUSION: Post trabeculectomy phacoemulsification, especially within 1 year, can cause poor prognosis of IOP control of UG eyes after trabeculectomy with MMC. PMID- 26989900 TI - A Surfactant-Induced Functional Modulation of a Global Virulence Regulator from Staphylococcus aureus. AB - Triton X-100 (TX-100), a useful non-ionic surfactant, reduced the methicillin resistance in Staphylococcus aureus significantly. Many S. aureus proteins were expressed in the presence of TX-100. SarA, one of the TX-100-induced proteins, acts as a global virulence regulator in S. aureus. To understand the effects of TX-100 on the structure, and function of SarA, a recombinant S. aureus SarA (rSarA) and its derivative (C9W) have been investigated in the presence of varying concentrations of this surfactant using various probes. Our data have revealed that both rSarA and C9W bind to the cognate DNA with nearly similar affinity in the absence of TX-100. Interestingly, their DNA binding activities have been significantly increased in the presence of pre-micellar concentration of TX-100. The increase of TX-100 concentrations to micellar or post-micellar concentration did not greatly enhance their activities further. TX-100 molecules have altered the secondary and tertiary structures of both proteins to some extents. Size of the rSarA-TX-100 complex appears to be intermediate to those of rSarA and TX-100. Additional analyses show a relatively moderate interaction between C9W and TX-100. Binding of TX-100 to C9W has, however, occurred by a cooperative pathway particularly at micellar and higher concentrations of this surfactant. Taken together, TX-100-induced structural alteration of rSarA and C9W might be responsible for their increased DNA binding activity. As TX-100 has stabilized the somewhat weaker SarA-DNA complex effectively, it could be used to study its structure in the future. PMID- 26989901 TI - Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome. AB - Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK) and lactate dehydrogenase A (LDHA) enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN) and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test). The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival. PMID- 26989902 TI - Expression of Heat Shock Protein 70 Gene and Its Correlation with Inflammatory Markers in Essential Hypertension. AB - OBJECTIVES: Hypertension is characterized by systemic high blood pressure and is the most common and important risk factor for the development of cardiovascular diseases. Studies have shown that the circulating levels of certain inflammatory markers such as tumor necrosis factor-alpha (TNF-alpha), interlukin-6 (IL-6), c reactive protein (CRP), and tumor suppressor protein-53 (p53) are upregulated and are independently associated with essential hypertension. However, mechanism of increase in the levels of HSP70 protein is not clear. No such studies are reported in the blood circulation of patients with essential hypertension. In the present study, we investigated the expression of circulating HSP70 at mRNA and protein levels and its relationship with other inflammatory markers in patients with essential hypertension. MATERIALS AND METHODS: We recruited 132 patients with essential hypertension and 132 normal controls from similar socio-economic geographical background. The expression of HSP70 at mRNA levels was determined by Real Time PCR and at protein levels by indirect Elisa and Western Blot techniques. RESULTS: We found a significantly higher expression of HSP70 gene expression (approximately 6.45 fold, P < 0.0001) in hypertensive patients as compared to healthy controls. A significant difference (P < 0.0001) in the protein expression of HSP70 was also observed in plasma of patients as compared to that of controls. CONCLUSION: Higher expression of HSP70 is positively correlated with inflammatory markers in patients with essential hypertension and this correlation could play an important role in essential hypertension. PMID- 26989904 TI - Intraoperative ultrasound and 5-ALA: the two faces of the same medal? AB - BACKGROUND: High Grade Gliomas (HGG) still remain the most demanding neuro oncological challenge. Several studies have confirmed that the extent of resection (EOR) correlates with increased survival in patients with HGGs. The Gross Total Resection (GTR) of HGGs can be difficult and challenging. For this reason, technologies to improve EOR have been of interest. The aim of this paper is to analyze advantages and limitations of both intra-operative fluorescence and intra-operative ultrasound (IOUS) resection techniques. METHODS: Our work deals with the comparison of one group of 15 patients treated with both tools (study group) with a control group of 15 patients in where only fluorescence was used. Post operative outcome are valued using Karnofsky Performance Status scale (KPS) while EOR are valued with MRI within 24 h after surgery. RESULTS: The difference between the postoperative KPS and between EOR in the 2 groups resulted not statistically significant considering p<0.05. In our experience 5-ALA has a limited sensitivity before starting resection while shows it's central role in identifying the tumor remnants after its removal. Conversely, IOUS is very useful in identifying the tumor before starting resection. After the tumor removal, the sensitivity of the ultrasound in identifying tumor remnants in the margins of the cavity decreased significantly. However, in one case, at the end of resection, we have not visualized any fluorescent tissue but we detect a residual of tumor using the IOUS. CONCLUSIONS: In our preliminary experience we observe that there are no significative advantages using IOUS plus 5-ALA. However we feel that IOUS is useful in first step of resection and fluorescence in the latest steps of operation. Therefore these two technologies could be considered the two faces of the same medal because they can help the surgeon to detect the tumor in all step of tumor removal. PMID- 26989905 TI - Treatment of intracerebral hemorrhage: a selective review and future directions. AB - Intracerebral hemorrhage (ICH) is a devastating disease. Sixty percent of survivors do not function independently at one year. Treatment of ICH costs approximately US$ 12.7 billion annually. To date no intervention has demonstrated clear efficacy in improving outcomes. The goal of this selective review is to provide an understanding of current treatment and discuss future directions. After a discussion of pathophysiology and societal impact, a synopsis of treatment options is reviewed, including: 1) open craniotomy; 2) catheter-based thrombolytic therapy; 3) endoscopic evacuation; and 4) ultrasonic lysis. Amongst other studies, we will discuss the results of STICH (International Surgical Trial in ICH) and MISTIE (Minimally Invasive Surgery plus Recombinant Tissue-type Plasminogen Activator for ICH Evacuation). We hope to provide a succinct, pragmatic review for the neurosurgical community on the current state of therapy and encourage novel ways to aggressively treat this burdensome disease. PMID- 26989903 TI - Feedback, Lineages and Self-Organizing Morphogenesis. AB - Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID- 26989906 TI - Ostwald-Driven Phase Separation in Bimetallic Nanoparticle Assemblies. AB - The compositional stability of bimetallic nanoparticles (NPs) is crucial for many applications. We have studied the coarsening of amorphous carbon-supported Au-Pd NPs during annealing at 873 K. Using scanning transmission electron microscopy and energy-dispersive spectroscopy measurements, we show that, despite a complete miscibility of the two metals, the particle assembly undergoes a phase separation during annealing, which leads to two distinct populations: Au-rich NPs with a mean radius of 3.5 nm and large Pd-rich NPs with a mean radius of 25 nm. Thermodynamic calculations and kinetic Monte Carlo simulations explain this behavior that is driven by the competition between surface and mixing energy and by the different mobilities of the two atomic species. PMID- 26989907 TI - Enhancing the Gelation and Bioactivity of Injectable Silk Fibroin Hydrogel with Laponite Nanoplatelets. AB - Regenerated silk fibroin (RSF) of Bombyx mori silk fiber is a promising natural material for bone defect repair. However, a lack of specific integrin and growth factor for osteoinduction significantly hinders its application in this area. In this study, the role of Laponite nanoplatelet (LAP), a bioactive clay that can promote osteoblast growth, in the formation of RSF hydrogel, as well as the various properties of RSF/LAP hybrid hydrogel, was closely investigated. The results indicate that LAP could serve as a medium to accelerate hydrophobic interaction among the RSF molecules and a disruptor to limit the growth of beta sheet domain during the gelation of RSF. Rheological measurement suggests that the RSF/LAP hydrogel is injectable as it displays thixotropy in the room temperature. Proliferation and differentiation results of the primary osteoblasts encapsulated in hydrogel show that RSF/LAP hydrogel can promote the cell proliferation and enhance the osteogenic differentiation. The transcript levels for alkaline phosphatase, osteocalcin, osteopontin, and collagen type I osteogenic markers obviously improve with RSF/LAP hydrogel compared to the controls at 14 days, especially with the higher contents of LAP. Overall, the results suggest that the RSF/LAP hydrogel have great potential to be utilized as an injectable biomaterial for irregular bone defect repair. PMID- 26989908 TI - Are conventional radiographs still of value? AB - PURPOSE OFREVIEW: To describe the most recent randomized-controlled trials (RCTs) and long-term observational studies (LOS) of RCTs with regard to radiological endpoints, and to interpret the results in the context of methodology. RECENT FINDINGS: Many RCTs include radiological endpoints, sometimes as primary endpoints, usually as secondary endpoints. The results of these RCTs prove that radiological assessment can still detect meaningful differences in the progression of structural RA-related damage between treatment arms. In addition, LOS provide the opportunity to investigate if radiological progression is stable over time in patients on treatment. Improvements in the selection of appropriate patients (enrichment) and in the analysis of radiological data allow a more meaningful interpretation of radiological data in RA clinical trials and LOS. SUMMARY: Radiological evaluation in RA clinical trials and observational studies is still valuable. Although subtle progression scores observed in clinical trials have limited direct clinical relevance, radiological treatment effects in trials may reflect subtle differences in clinical efficacy between treatment arms, and radiological progression may be considered a reflection of historic disease activity. PMID- 26989909 TI - New concepts of clinical trials in rheumatoid arthritis: a boom of noninferiority trials. AB - PURPOSE OF REVIEW: The purpose is to describe the most recent randomized controlled trials (RCT) in patients with rheumatoid arthritis that had a noninferiority design, and to focus on methodological aspects of noninferiority. RECENT FINDINGS: In 2014 and 2015 10 different RCTs with a noninferiority-design could be identified, in comparison to only a few in the decade before. Most RCTs had a rather small sample size, and had ill-defined noninferiority-margins, or noninferiority-margins without comprehensible clinical meaning. Six of the 10 trials indeed arrived at a conclusion of 'noninferiority'; four did not. Interestingly, many of the RCTs were pragmatic studies comparing strategies, and the investigators were neither blind to the treatment nor to the outcome. In addition, the treatments were often adaptive (e.g. treat-to-target approach). These characteristics are considered built-in incentives for noninferiority. SUMMARY: In the competitive pharmaceutical landscape of rheumatoid arthritis, with many effective drugs and strategies, it is no surprise that the number of noninferiority-trial (sharply) rises. But noninferiority trials are difficult to design, conduct, and interpret, and many principles of noninferiority-trial designs are currently ignored, which may jeopardise their conclusions to some extent. PMID- 26989910 TI - End-Stage Renal Disease From Cast Nephropathy in a Teenager With Neuroendocrine Carcinoma. AB - Cast nephropathy is the most common manifestation of renal injury in patients with multiple myeloma but is rarely reported in other conditions. We are reporting our experience in caring for a teenager with a metastatic neuroendocrine carcinoma who developed rapidly progressive kidney injury that advanced to end-stage renal disease. On renal biopsy extensive tubular necrosis and intratubular eosinophilic casts were noted. This previously unreported finding should prompt oncologists to closely monitor for such a complication in patients with secretory tumors. Whether early plasmapheresis could be of benefit, as has been tried in multiple myeloma, remains to be determined. PMID- 26989912 TI - Renal Late Effects After the Treatment of Unilateral Nonsyndromic Wilms Tumor. AB - Wilms tumor is the most common renal malignancy of childhood. Because of the improvement in prognosis and the increase in survival rates, long-term consequences of the treatment for Wilms tumor are of greater concern. We investigated late renal effects of the treatment on 50 survivors of nonsyndromic unilateral Wilms tumor. After the second year since the cessation of treatment, the glomerular filtration rate (GFR), urinary protein excretion, urinary beta2 microglobulin levels, and blood pressure as well as the general health status were assessed. Results were analyzed for correlation with clinical variables, chemotherapy, and radiotherapy as possible risk factors. At a median follow-up time of 8.8 years (mean=10.9; range, 2.3 to 35.4 y), none of the patients developed end-stage renal disease. Compensatory hypertrophy was observed in 68% of the cases. The median maximum bipolar length was significantly higher in patients diagnosed after the age of 36 months. Eleven (22%) and 2 (4%) of the 50 patients were hypertensive at the time of the diagnosis and the study, respectively. Similarly, median GFR values were significantly lower at the time of diagnosis, although at the time of the study, all patients had normal GFR values. With longer follow-up intervals, especially after 10 years, a significant decreasing trend in the GFR was observed (P=0.002). PMID- 26989911 TI - Prevalence and Predictors of Overweight and Obesity Among a Multiethnic Population of Pediatric Acute Lymphoblastic Leukemia Survivors: A Cross-Sectional Assessment. AB - As previous studies of obesity in survivors of pediatric acute lymphoblastic leukemia (ALL) have primarily been conducted among non-Hispanic white survivors or children treated on older protocols, our objective was to describe the prevalence and correlates of overweight status among an ethnically diverse population of pediatric ALL survivors, largely treated with more contemporary therapies. We evaluated the overweight/obesity status of pediatric ALL survivors (n=406) followed in the Texas Children's Cancer Center between 2004 and 2014. Survivors were classified as underweight, normal weight, overweight, or obese on the basis of their body mass index at their most current follow-up visit. Our results showed that Hispanic ethnicity (39% of the subjects) was associated with being overweight (adjusted odds ratio=1.88; 95% confidence interval, 1.13-3.14) or obese (adjusted odds ratio=2.84; 95% confidence interval, 1.59-5.06) at follow up, even after adjusting for cranial radiotherapy (CRT) exposure. Body mass index z-score at diagnosis was also associated with overweight/obesity at follow-up. In addition, there was a statistically significant interaction between younger age at diagnosis and CRT, indicating that younger age at diagnosis was associated with obesity among patients who received CRT. These findings may help identify pediatric ALL patients that are at increased risk of being overweight or obese after treatment. PMID- 26989913 TI - Inflammatory Myofibroblastic Tumor of the Heart in the Infant: Review of the Literature. AB - Primary heart tumors are extremely rare, constituting approximately 0.02% of all malignancies. Inflammatory myofibroblastic tumor (IMT) constitutes <5% of primary heart tumors. Until now, IMT of the heart has been described in 21 infants below 1 year of age. Its etiology remains unknown. IMT usually develops within the right atrial and ventricular endocardium. The main clinical symptoms reported in the affected infants involved increasing respiratory failure, cyanosis, and heart murmurs. Histopathologically, IMT is characterized by the myofibroblast proliferation with inflammatory infiltrates composed of plasmocytes, lymphocytes, and histiocytes. Tumor resection is the treatment of choice in IMT. Such tumor location is associated with the high risk of perioperative failure. Steroid therapy and chemotherapy is reported in the literature as a nonsurgical treatment alternative. Here, we present a review of clinical symptoms, diagnostic and treatment options, based on published case reports of IMT in infants, including our 11-month-old patient with IMT located within the pericardium. PMID- 26989914 TI - The Effects of Hospital Length of Stay on Readmissions for Children With Newly Diagnosed Acute Lymphoblastic Leukemia. AB - Although regimens for induction therapy in children with acute lymphoblastic leukemia (ALL) are similar across the United States, typical practice with regard to inpatient length of stay (LOS) varies by institution. US children's hospitals were categorized by typical induction LOS; and readmissions, pediatric intensive care unit (PICU) admissions, and average adjusted charges were compared for the first 30 days from initial admission. Using Pediatric Health Information System data, we extracted ALL induction admissions from 2007 to 2013. We categorized hospitals into 3 categories based on median LOS: short (<=7 d), medium (8 to 15 d), or long (>=16 d). Median LOS varied from 5 to 31 days across hospitals. Thirty-day median inpatient costs per patient ranged from $32 K for short LOS, $40 K for medium LOS, and $47 K for long LOS. Compared with short LOS hospitals (n=14), medium LOS (n=8) and long LOS hospitals (n=8) had lower odds of PICU readmissions (odds ratio [OR], 0.68; P=0.0124 and OR, 0.31; P<0.001, respectively), and long LOS hospitals had lower odds of any readmission (OR, 0.44; P<0.0001). Average LOS for children with newly diagnosed ALL varies widely by institution. Children's hospitals that typically admit new ALL patients for >7 days have fewer PICU readmissions but substantial increase in total induction inpatient costs. PMID- 26989916 TI - HPV-16 Detected in One-Fourth Eyes With Retinoblastoma: A Prospective Case control Study From North India. AB - The incidence of nonfamilial retinoblastoma (RB) is believed to be higher in developing countries. The reports on association of human papillomavirus (HPV) with RB are limited and contradictory. The aim was to investigate the prevalence of HPV in RB tumor tissue. In the prospective study, consecutive eyes enucleated for RB from patients lacking a family history of RB were enrolled as cases over a 3-year period. Controls included donor eyes obtained from the eye bank. Normal retinal tissue from the donor eyes and tumor tissue from eyes with RB was subjected to DNA isolation. Polymerase chain reaction followed by dot-blot hybridization was performed to detect 21 HPV genotypes. The study cohort included 39 RB and 42 normal retinal tissues. A positive result for HPV-polymerase chain reaction was obtained in 10 (25.6%) tumor tissues and none of the control eyes. HPV-16 was the only subtype detected. Socioeconomic status (P=0.58) or maternal age (P=0.58) was not associated with presence of HPV. All HPV-positive patients had undergone a vaginal delivery (P=0.60). HPV-16 was detected in one-fourth cases of nonfamilial RB. None of the control cases (donor eyes) tested positive. Implication of the presence of HPV in RB tissue and role in carcinogenesis needs further elucidation. PMID- 26989917 TI - Broadening horizons. PMID- 26989918 TI - Treatment of hepatitis C virus infection in intravenous drug users. AB - BACKGROUND: Hepatitis C virus (HCV) infection is common among intravenous drug users, and because of the long latent period, HCV liver disease is set to increase. OBJECTIVES: We sought to examine practice guidelines regarding treatment of HCV in drug users and to review the evidence for current practices. METHODS: A structured search of the Pubmed database, websites of the National Institute for Clinical Excellence and national and international expert groups and opinion of independent experts in the field. RESULTS AND CONCLUSIONS: All those infected with HCV need to be assessed to ascertain whether they have active ongoing viral replication and the extent of liver damage. HCV-infected individuals should be educated about the modes of transmission and means of reducing the risk of infecting others. They should also be advised to avoid cofactors (especially alcohol) that accelerate the progression of liver disease. Specific treatment with antivirals can cause viral clearance and prevent the progression of liver disease. Therapy is effective in those on opiate-replacement treatments and also in motivated individuals who continue to use intravenous drugs. The decision whether to treat drug users should be made jointly by specialists in the management of viral hepatitis and addiction on a case-by-case basis. Current combination drug regimens are expensive but are claimed to be cost effective, and are certainly much less costly than managing end-stage liver disease. In addition to satisfactory sustained viral response rates, other benefits such as a beneficial effect on drug habit, self-esteem and rehabilitation have been reported. Encouraging suitable drug users to take-up and comply with treatment seems to be more easily achieved in supportive drug dependency unit settings (rather than the more formal surroundings of a hospital clinic). PMID- 26989915 TI - Pediatric Brain Tumors: Current Knowledge and Therapeutic Opportunities. AB - Great progress has been made in many areas of pediatric oncology. However, tumors of the central nervous system (CNS) remain a significant challenge. A recent explosion of data has led to an opportunity to understand better the molecular basis of these diseases and is already providing a foundation for the pursuit of rationally chosen therapeutics targeting relevant molecular pathways. The molecular biology of pediatric brain tumors is shifting from a singular focus on basic scientific discovery to a platform upon which insights are being translated into therapies. PMID- 26989919 TI - Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments. AB - BACKGROUND: New evidence is emerging regarding abnormalities of hypothalamic pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed. OBJECTIVE: To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone. METHOD: A selective review of the literature. RESULTS: The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments. CONCLUSION: Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited. PMID- 26989920 TI - Double depression: its morbidity and management in a community setting. AB - BACKGROUND: Double depression, the combination of major depression and dysthymia, is associated with poor health-related quality of life (HRQoL) and increased health service utilization. OBJECTIVE: To determine the prevalence of double depression, its associated morbidity and use of health services and antidepressants. METHODS: A random and representative sample of the South Australian general population was interviewed. The mood module of the Primary Care Evaluation of Mental Disorders (PRIME-MD), the Short-Form Health Status Questionnaire (SF-36) and Assessment of Quality of Life (AQoL) instruments were administered, and data relating to health service utilization, antidepressant use and role functioning were collected. RESULTS: Double depression was present in 3.3% of the population. The use of health services was significantly higher in this group than those with no depression, or dysthymia or major depression alone. Only 15.2% had attended a community health service, 18.2% had seen a psychiatrist, 10.1% a psychologist, 16.2% a social worker and 9.1% any other counsellor in the last month. While 41.4% were currently taking an antidepressant, the average doses of the two most commonly prescribed antidepressants were below the maximum recommended doses, and the use of antidepressant augmentation strategies was also minimal. CONCLUSIONS: While double depression is associated with increased morbidity and use of health services, the optimum use of both pharmacological and nonpharmacological treatments is clearly lacking in this community sample. PMID- 26989921 TI - Brain activation measured using functional magnetic resonance imaging during the Tower of London task. AB - BACKGROUND: Individuals with traumatic brain injury (TBI) often suffer from a number of enduring cognitive impairments such as in attention, memory, speed of processing information and dual-task performance. OBJECTIVE: The aim of this study was to assess the patterns of regional brain activation in response to the Tower of London (ToL) task in a group of patients suffering from chronic TBI using functional magnetic resonance imaging (fMRI). METHODS: fMRI was performed during performance of the ToL planning task in 10 patients suffering from severe TBI and in 10 age- and sex-matched controls using a 3 T magnetic resonance scanner. RESULTS: Performance data showed no difference in response accuracy between the TBI group and the healthy control group. Statistical parametric brain maps showed that the TBI group activates larger and additional areas of the cerebral cortex than the healthy control group both for tasks and for a subtraction contrast between the tasks. CONCLUSIONS: The results of this study are interpreted as a cortical reorganization inside the executive system of vigilance and working memory in patients with TBI. Both parietal and frontal areas are recruited to compensate for damaged brain tissue. PMID- 26989922 TI - Structural brain correlates of alcohol and cannabis use in recreational users. AB - BACKGROUND: Previous studies on substance-dependent populations have shown that age of first use and duration of use are associated with alterations in regional brain volumes. However, it is not clear whether such alterations are factors that predispose young people to use, and so are also present in recreational users, or are a consequence of chronic exposure to substances and/or comorbid psychopathology. OBJECTIVE: To investigate relationships between key brain structures and parameters of alcohol and cannabis use, in otherwise healthy male recreational users. METHOD: High-resolution magnetic resonance imaging was used to measure hippocampal, amygdala, whole-brain and intracranial cavity (ICC) volumes in 22 young men with a history of both alcohol and cannabis use. RESULTS: Linear regression analyses with hippocampal, amygdala and whole-brain volumes as the dependent variables and age and ICC as covariates were performed. Findings showed that use of cannabis and alcohol at an earlier age were independently predictive of larger amygdala volumes, whereas longer duration of cannabis use was predictive of smaller hippocampal volumes. CONCLUSIONS: Our findings offer preliminary support for a relationship between patterns of substance use and regional brain volumes in recreational users. It is speculative, but possible that this relationship is an evidence of a neurobiological vulnerability to drug taking behaviour. PMID- 26989923 TI - Magnetic resonance imaging findings in a case of stroke-related peduncular hallucinosis. AB - BACKGROUND: Peduncular hallucinosis is a rare stroke-related phenomenon that may occur in cases of ischemic lesions localized in the cerebral peduncles, the pons, the upper midbrain or the thalamus and is mostly characterized by transient visual hallucinations. CASE PRESENTATION: We report the case of an insufficiently treated hypertensive patient who presented with constantly elevated blood pressure values and persistent visual hallucinations, which ceased a few hours later after medically achieved blood pressure normalization. Magnetic resonance imaging (MRI) revealed a symmetric paramedian ischemic lesion of the upper pons, which seems to be the cause of this case of peduncular hallucinosis. CONCLUSION: Although uncommon, this entity needs to be differential diagnostically considered in cases of transient visual hallucinations in persons with known vascular risk profile. MRI can be a useful diagnostic tool. PMID- 26989924 TI - Standardized Indications to Assist in the Safe Thoracoscopic Repair of Congenital Diaphragmatic Hernia in Neonates. AB - BACKGROUND: To analyze the early outcome of thoracoscopic repair (TR) of neonatal congenital diaphragmatic hernia (CDH) with standardized indications. METHODS: Clinical data of 14 neonates with CDH who underwent TR from September 2013 to August 2014 were retrospectively analyzed. SELECTION CRITERIA: weight beyond 2.0 kg; liver in the abdomen; no intestinal obstruction; no severe cardiopulmonary anomalies; not required high-frequency oscillatory ventilation or extracorporeal membrane oxygenation. Timing of surgery: mean arterial blood pressure normal for gestational age; preductal saturation levels of 85%-95% on fractional inspired oxygen below 50%; lactate below 3 mmol/L; urine output more than 2 mL/kg/h. Fourteen cases in the historical control group who underwent open repair (OR) with the same physiological status were reviewed for comparison. RESULTS: Demographic features were similar between the TR group and OR group. The TR group had a higher intraoperative mean PaCO2 (48 +/- 8 mmHg versus 39 +/- 6 mmHg, P = .0024) and mean arterial pH (7.30 +/- 0.06 versus 7.39 +/- 0.06, P = .0005), but no differences in lactate (0.93 +/- 0.16 mmol/L versus 0.98 +/- 0.14 mmol/L, P = .3869). Longer operation time was found in the TR group (116 +/- 27 minutes versus 74 +/- 25 minutes, P = .0002). No recurrence was observed in groups within the first year of life follow-up. CONCLUSIONS: With selection criteria and timing, TR of CDH in neonates can be performed safely and successfully. PMID- 26989925 TI - The Impact of Resident Training on Communication with Families in the Intensive Care Unit. Resident and Family Outcomes. AB - RATIONALE: In high-acuity settings such as intensive care units (ICUs), the quality of communication with patients' families is a particularly important component of care. Evidence shows that ICU communication is often inadequate and can negatively impact family outcomes. OBJECTIVES: To assess the impact of a communication training program on resident skills in communicating with families in an ICU and on family outcomes. METHODS: We conducted a prospective, single site educational intervention study. The intervention featured a weekly required communication training program (4 h total) during the ICU rotation, which included interactive discussion, and role play with immediate feedback from simulated family members. All internal medicine residents on ICU rotation between July 2012 and July 2014 were invited to participate in the study. Family members who had a meeting with an enrolled resident were approached for a survey or interview. The primary outcome was family ratings of how well residents met their informational and emotional needs. MEASUREMENTS AND MAIN RESULTS: The response rate for the resident baseline survey was 93% (n = 149 of 160), and it was 90% at postcourse and 84% at 3-month follow-up. Of 303 family members approached, 237 were enrolled. Enrolled family members who had a confirmed meeting with a resident were eligible to complete a survey or interview. The completion rate was 86% (n = 82 of 95). Family members were more likely to describe residents as having "fully met" (average rating of 10/10 on 0-10 scale) their informational and emotional needs when the resident had completed two or three course sessions (84% of family members said conversation with these residents "fully met" their needs), as compared with residents who had taken one session or no sessions (25% of family members said needs were "fully met") (P < 0.0001). Residents described improvements across all domains. All differences are statistically significant, most with large effect sizes. CONCLUSIONS: At our institution, an on-site communication training program designed for integration into medical residency programs was associated with strongly positive family member outcomes and significant improvements in residents' perceived skills. This intervention may serve to prepare residents for optimal communications with patients and family members in ICUs and elsewhere. PMID- 26989927 TI - Dealing with Uncertainty in CT Images. PMID- 26989928 TI - Elbow Imaging in Sport: Sports Imaging Series. AB - Elbow pain is a frequent presenting symptom in athletes, particularly athletes who throw. The elbow can be injured as a result of acute trauma, such as a direct blow or a fall onto an outstretched hand or from chronic microtrauma. In particular, valgus extension overload during the throwing motion can precipitate a cascade of chronic injuries that can be debilitating for both casual and high performance athletes. Prompt imaging evaluation facilitates accurate diagnosis and appropriate targeted interventions. PMID- 26989929 TI - Secretin-enhanced MR Imaging of the Pancreas. AB - Secretin is a hormone that stimulates the exocrine pancreatic secretion of bicarbonate-rich fluid from the acinar cells of the pancreas that accumulates within the pancreatic ductal lumen. The exogenous administration of secretin improves the visualization of pancreatic ducts at magnetic resonance (MR) cholangiopancreatography (MRCP), because of an enlargement of the pancreatic duct system and an increase of the fluid content within the lumen of the pancreatic ducts, responsible of an increase of MR signal. In this review, the technique of secretin-enhanced MRCP, which has the aim to depict the whole pancreatic duct system, the biliary tree, the major and minor papillae, and the duodenum, will be described. Because of the anatomic contiguity between the pancreas and the gastrointestinal tract, the presence of fluid within the stomach may overlap with the pancreatic duct system and therefore the pancreatic duct may be difficult to visualize, representing a potential source of diagnostic pitfalls. The technique to reduce the signal intensity of the static fluid present within the stomach and in the duodenal lumen is also described. The technique of secretin administration will be illustrated, with emphasis on the synchronization of secretin administration and MR image acquisition. Furthermore, the frequency and number of MRCP images necessary to achieve a temporal resolution adequate to visualize the physiologic changes in the pancreatic gland, induced by the administration of secretin, is described. The assessment of pancreatic, morphologic, and functional response to the administration of secretin, as depicted on MRCP images, will be illustrated. Finally, the indications for secretin-enhanced MRCP will be discussed to define which patients will benefit from secretin-enhanced MR imaging for their treatment planning. ((c)) RSNA, 2016. PMID- 26989931 TI - Case 228: Mueller-Weiss Disease. AB - History A 53-year-old woman presented to the hospital for evaluation of progressive long-standing left dorsomedial foot pain, which was made worse with weight bearing. There was no history of trauma. Prior assessments were performed at another facility, and she did not to respond to conservative therapy. History was negative for systemic disorders. Physical examination revealed tenderness over the left talonavicular joint and flattening of the medial arch of the left foot. Otherwise, the findings were unremarkable. A basic serum chemistry test and complete blood count revealed no abnormal findings. The patient underwent routine weight-bearing radiography of her left foot and weight-bearing computed tomography (CT) of both feet. PMID- 26989932 TI - Systemic Effects of Local Tumor Ablation: Oncogenesis and Antitumor Induced Immunity. PMID- 26989933 TI - Gadolinium Deposition in the Brain: Do We Know Enough to Change Practice? PMID- 26989934 TI - Quantitative Dynamic Contrast-enhanced MR Imaging in Posttreatment Glioblastoma: Possible Limitations of Short Acquisition Time. PMID- 26989935 TI - MR Imaging in the Assessment of Endometrial Cancer. PMID- 26989936 TI - The Alzheimer Structural Connectome: Changes in Cortical Network Topology with Increased Amyloid Plaque Burden. PMID- 26989937 TI - Beyond the Cuff: MR Imaging of Labroligamentous Injuries in the Athletic Shoulder. PMID- 26989938 TI - Quiet Submillimeter MR Imaging of the Lung Is Feasible with a PETRA Sequence at 1.5 T. PMID- 26989940 TI - Impact of exogenous organic carbon on the removal of chemicals of concern in the high rate nitrifying trickling filters. AB - The application of fixed bed high rate nitrifying trickling filters (NTFs) for the removal of track organic chemicals of concern (CoC) is less well known than their application to nutrient removal in water treatment. Particularly, the effect of exogenous organic carbon substrate (sucrose) loading on the performance of NTFs is not well understood. A laboratory-scale NTF system was operated in recirculation mode, with the objective of removing ammonia and CoC simultaneously. The efficiency of a high rate NTF for removal both of low concentration of ammonia (5 mg NH4-N L(-1)) and different concentrations of CoC in the presence of an exogenous organic carbon substrate (30 mg total organic carbon (TOC) L(-1)) was investigated. In the presence of exogenous organic carbon, the results demonstrated that the high rate NTF was able to successfully remove most of the CoCs investigated, with the removal ranging from 20.2% to 87.54%. High removal efficiencies were observed for acetaminophen (87.54%), bisphenol A (86.60%), trimethoprim (86.24%) and 17alpha-ethynylestradiol (80.60%). It was followed by the medium removal efficiency for N, N-diethyl-m toluamide (61.31%) and atrazine (56.90%). In contrast, the removal of caffeine (28.43%) and benzotriazole (20.20%) was poorer in the presence of exogenous organic carbon. The removal efficiency for CoC was also compared with the results obtained in our previous study in the absence of exogenous organic carbon. The results showed that the addition of exogenous organic carbon was able to improve the removal of some of the CoC. Significant TOC percentage removals (45.68% 84.43%) and ammonia removal rate (mean value of 0.44 mg NH4-N L(-1) h(-1)) were also achieved in this study. The findings from this study provide valuable information for optimising the efficiency of high rate NTF for the removal of ammonia, CoC and TOC. PMID- 26989941 TI - Beneficial role of bacterial endophytes in heavy metal phytoremediation. AB - Phytoremediation is an emerging technology that uses plants and their associated microbes to clean up pollutants from the soil, water and air. In recent years, phytoremediation assisted by bacterial endophytes has been highly recommended for cleaning up of metal polluted soils since endophytic bacteria can alleviate metal toxicity in plant through their own metal resistance system and facilitate plant growth under metal stress. Endophytic bacteria improve plant growth in metal polluted soils in two different ways: 1) directly by producing plant growth beneficial substances including solubilization/transformation of mineral nutrients (phosphate, nitrogen and potassium), production of phytohormones, siderophores and specific enzymes; and 2) indirectly through controlling plant pathogens or by inducing a systemic resistance of plants against pathogens. Besides, they also alter metal accumulation capacity in plants by excreting metal immobilizing extracellular polymeric substances, as well as metal mobilizing organic acids and biosurfactants. The present work aims to review the progress of recent research on the isolation, identification and diversity of metal resistant endophytic bacteria and illustrate various mechanisms responsible for plant growth promotion and heavy metal detoxification/phytoaccumulation/translocation in plants. PMID- 26989942 TI - Examining water quality effects of riparian wetland loss and restoration scenarios in a southern ontario watershed. AB - Wetland conservation has two important tasks: The first is to halt wetland loss and the second is to conduct wetland restoration. In order to facilitate these tasks, it is important to understand the environmental degradation from wetland loss and the environmental benefits from wetland restoration. The purpose of the study is to develop SWAT based wetland modelling to examine water quality effects of riparian wetland loss and restoration scenarios in the 323-km(2) Black River watershed in southern Ontario, Canada. The SWAT based wetland modelling was set up, calibrated and validated to fit into watershed conditions. The modelling was then applied to evaluate various scenarios of wetland loss from existing 7590 ha of riparian wetlands (baseline scenario) to 100% loss, and wetland restoration up to the year 1800 condition with 11,237 ha of riparian wetlands (100% restoration). The modelling was further applied to examine 100% riparian wetland loss and restoration in three subareas of the watershed to understand spatial pattern of water quality effects. Modelling results show that in comparing to baseline condition, the sediment, total nitrogen (TN), and total phosphorus (TP) loadings increase by 251.0%, 260.5%, and 890.9% respectively for 100% riparian wetland loss, and decrease by 34.5%, 28.3%, and 37.0% respectively for 100% riparian wetland restoration. Modelling results also show that as riparian wetland loss increases, the corresponding environmental degradation worsens at accelerated rates. In contrast, as riparian wetland restoration increases, the environmental benefits improve but at decelerated rates. Particularly, the water quality effects of riparian wetland loss or restoration show considerable spatial variations. The watershed wetland modelling contributes to inform decisions on riparian wetland conservation or restoration at different rates. The results further demonstrate the importance of targeting priority areas for stopping riparian wetland loss and initiating riparian wetland restoration based on scientific understanding of watershed wetland effects. PMID- 26989943 TI - Significant cognitive improvement with cholinesterase inhibition in AD with cerebral amyloid angiopathy. PMID- 26989944 TI - Charcot-Marie-Tooth type 2 and distal hereditary motor neuropathy: Clinical, neurophysiological and genetic findings from a single-centre experience. AB - OBJECTIVES: CMT is a group of heterogeneous motor and sensory neuropathies divided into demyelinating (CMT1) and axonal forms (CMT2). Distal Hereditary Motor Neuropathy (dHMN) is a motor neuropathy/neuronopathy which resembles CMT. Final genetic diagnosis is poor in CMT2 and in dHMN when compared with CMT1. Our aim is to report clinical, neurophysiological and genetic findings in a cohort of patients with axonal inherited neuropathies. PATIENTS AND METHODS: We report clinical, neurophysiological and genetic findings from 45 patients with CMT2 or dHMN, coming from 39 unrelated families, observed in our Institute of Neurology over a 20-year period. RESULTS: Clinical and electrophysiological examinations showed that 38 patients had CMT2 and 7 patients presented dHMN. Extensive genetic evaluation showed 6 mutations in MFN2, 4 mutations in HSPB1, 2 mutations in BSCL2, 3 mutations in GJB1, 1 mutation in MPZ. CONCLUSION: Since next-generation sequencing will not be easily accessible, epidemiological data and clinical "phenotyping" remain the best strategy for clinicians to reach a correct genetic diagnosis in CMT2 and dHMN patients. PMID- 26989945 TI - Molecular characterization, phylogeny analysis and pathogenicity of a Muscovy duck adenovirus strain isolated in China in 2014. AB - This study aimed to characterize a novel adenovirus (AdV) isolated from diseased Muscovy ducks in China. After the AdV was successfully propagated in duck embryo fibroblasts, the morphological and physicochemical properties of the virions were studied by electron microscopy and different tests. The results of the analyses were in conformity with AdV properties. The full genome sequence was determined and analyzed. The new isolate (named CH-GD-12-2014) shared over 91% sequence identity with duck AdV-2 representing the species Duck aviadenovirus B. The most important distinguishing feature between the two DAdV strains was the presence of a second fiber gene in the Chinese isolate. Phylogeny reconstruction confirmed the affiliation of the virus with goose and duck AdVs in the genus Aviadenovirus. Experimental infection resulted in embryo death, and intramuscular inoculation provoked morbidity and mortality among ducks and chickens. PMID- 26989946 TI - Paclitaxel-coated balloon angioplasty for de novo coronary lesions: a long-term follow-up study. AB - BACKGROUND: Paclitaxel-coated balloons (PCB) have been demonstrated to be successful for the treatment of in-stent restenosis. Although their role in the treatment of de novo lesions has not been fully clarified, they are often used for this indication. This prospective study evaluated the long-term efficacy and safety of the SeQuent(r) Please PCB (B. Braun, Melsungen, Germany) angioplasty for de novo coronary lesions in routine real-world practice. METHODS: Between January 2010 and January 2012, all consecutive patients with de novo coronary lesions treated with the SeQuent(r) Please PCB at our institution were included. The primary endpoint was the clinically driven target lesion revascularization (TLR) rate at 36 months. The secondary endpoint was the rate of major adverse cardiac events (MACE: cardiac death, myocardial infarction [MI], and TLR). RESULTS: Fifty-three patients with 56 lesions were included. The mean reference vessel diameter was 2.4+/-0.4 mm and the mean target lesion length was 18.1+/-6.2 mm. Procedural success was 98.2%. Coronary dissection occurred in 7 patients (12.5%) and no vessel thrombosis was documented. Additional BMS was implanted in 14 target lesions (25%). Follow-up rate was 94.3%. The TLR rate at 36 months was 5.4%. The MACE rate was 8.9%, with 1.8 % cardiac death and 3.6% MI. CONCLUSIONS: Treatment of de novo coronary lesions with the SeQuent(r) Please PCB provides good clinical outcomes demonstrated by the low TLR rate and low MACE rates at long-term follow-up. PMID- 26989947 TI - Left main percutaneous coronary intervention in ACS or stable coronary artery disease: acute and long-term results. AB - BACKGROUND: The aim of this study was to assess in-hospital and long-term results of the novo unprotected left main (UPLM) percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) or stable coronary artery disease (CAD), in an unselected population admitted to a single high- volume cath-lab without on-site cardiac surgery. METHODS: From 2008 to 2011, among 317 PCI performed in patients with the novo UPLM stenosis, 49 patients presented ST elevation myocardial infarction (STEMI), 152 non ST-elevation MI/unstable angina (NSTEMI/UA), 116 stable CAD. RESULTS: In-hospital mortality was 20% in STEMI, 5.3% in NSTEMI/UA and 1.7% in stable CAD patients (P<0.001). Two-year total mortality was 24.5%, 25.6% and 6% in the 3 groups, and cardiac death was 20%, 13.8% and 3.4% (P=0.002). Left main target lesion revascularization (TLR) was similar in the 3 groups, as the clinically-driven TLR (10% vs. 11% vs. 7.7%, P=0.642), with neither definite nor probable stent thrombosis. Multivariate analysis showed the following independent predictors of 2-year mortality: bare metal stent use (OR 4.53, P<0.001), Syntax Score >32 (OR 3.53, P=0.012), ACS as the indication (OR 3.24, P=0.012), peripheral artery disease (OR 2.20, P=0.042), and age >75 years (OR 2.09, P=0.05). CONCLUSIONS: Our experience showed acceptable results of UPLM PCI in STEMI patients, where short-term prognosis was related to hemodynamic conditions, good results in NSTEMI/UA patients where mortality increased in the follow-up due to comorbidities, and very good results in patients with stable CAD. PMID- 26989948 TI - Effects of Arnica comp.-Heel(r) on reducing cardiovascular events in patients with stable coronary disease. AB - BACKGROUND: The purpose of the study was to evaluate the effectiveness of the treatment with one tablet a day of a low dose multicomponent medication (Arnica comp.-Heel(r) tablets) with anti-inflammatory properties in order to reduce the risk of cardiovascular events in patients with clinically stable coronary disease. The presence of inflammatory cells in atherosclerotic plaques of patients with stable coronary disease indicates the possibility to act by inhibiting the inflammatory phenomenon with Arnica comp.-Heel(r) tablets reducing the risk of instability of the plaque and, consequently, improving the clinical outcome in patients with stable coronary disease. METHODS: Within this retrospective observational spontaneous clinical study 44 patients (31 males and 13 females) all presenting stable coronary artery disease were evaluated; 25 subjects were treated with only acetylsalicylic acid and/or clopidogrel in association with statins (standard therapeutic protocol) while for the other 18 subjects the standard therapeutic protocol was integrated with Arnica comp. Heel(r) (one sublingual tablet/day). The primary outcome was to evaluate the incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or non cardioembolic ischemic stroke. RESULTS: The evaluation of the primary outcome showed that in the group of patients (18) who received the standard therapeutic protocol plus Arnica comp.-Heel(r) only one cardiovascular event was registered (5.6%) while in the group treated only with standard therapy 4 events were recorded in 25 patients (16%). CONCLUSIONS: The treatment with Arnica comp. Heel(r) (one tablet/day) in combination with standard therapies for secondary prevention is effective in reducing the incidence of cardiovascular events in patients with stable coronary artery disease. PMID- 26989949 TI - If you're scared, you play dead! PMID- 26989950 TI - PARENT: A Parallel Software Suite for the Calculation of Configurational Entropy in Biomolecular Systems. AB - Accurate estimation of configurational entropy from the in silico-generated biomolecular ensembles, e.g., from molecular dynamics (MD) trajectories, is dependent strongly on exhaustive sampling for physical reasons. This, however, creates a major computational problem for the subsequent estimation of configurational entropy using the Maximum Information Spanning Tree (MIST) or Mutual Information Expansion (MIE) approaches for internal molecular coordinates. In particular, the available software for such estimation exhibits serious limitations when it comes to molecules with hundreds or thousands of atoms, because of its reliance on a serial program architecture. To overcome this problem, we have developed a parallel, hybrid MPI/openMP C++ implementation of MIST and MIE, called PARENT, which is particularly optimized for high-performance computing and provides efficient estimation of configurational entropy in different biological processes (e.g., protein-protein interactions). In addition, PARENT also allows for a detailed mapping of intramolecular allosteric networks. Here, we benchmark the program on a set of 1-MUs-long MD trajectories of 10 different protein complexes and their components, demonstrating robustness and good scalability. A direct comparison between MIST and MIE on the same dataset demonstrates a superior convergence behavior for the former approach, when it comes to total simulation length and configurational-space binning. PMID- 26989951 TI - MoS2-InGaZnO Heterojunction Phototransistors with Broad Spectral Responsivity. AB - We introduce an amorphous indium-gallium-zinc-oxide (a-IGZO) heterostructure phototransistor consisting of solution-based synthetic molybdenum disulfide (few layered MoS2, with a band gap of ~1.7 eV) and sputter-deposited a-IGZO (with a band gap of ~3.0 eV) films as a novel sensing element with a broad spectral responsivity. The MoS2 and a-IGZO films serve as a visible light-absorbing layer and a high mobility channel layer, respectively. Spectroscopic measurements reveal that appropriate band alignment at the heterojunction provides effective transfer of the visible light-induced electrons generated in the few-layered MoS2 film to the underlying a-IGZO channel layer with a high carrier mobility. The photoresponse characteristics of the a-IGZO transistor are extended to cover most of the visible range by forming a heterojunction phototransistor that harnesses a visible light responding MoS2 film with a small band gap prepared through a large area synthetic route. The MoS2-IGZO heterojunction phototransistors exhibit a photoresponsivity of approximately 1.7 A/W at a wavelength of 520 nm (an optical power of 1 MUW) with excellent time-dependent photoresponse dynamics. PMID- 26989952 TI - Distinct Clinical Phenotype of Corneal Dystrophy Predicts the p.(Leu450Trp) Substitution in COL8A2. AB - PURPOSE: The p.(Leu450Trp) substitution in Collagen, Type VIII, Alpha 2 (COL8A2) is associated with an early-onset corneal dystrophy. Here we identify distinct anterior corneal and keratorefractive changes associated with this disease and replicate its distinguishing endothelial characteristics in a new family. METHODS: We reviewed clinical data from a large family associated with the p.(Leu450Trp) COL8A2 mutation. We compared clinical photographs and keratometry over an 11-year period. We sought to replicate these findings, and after a 40 year-old male subject presented similarly, we obtained a peripheral blood sample and sequenced COL8A2. RESULTS: Of 10 individuals with the p.(Leu450Trp) substitution, clinical records noted corneal edema in 6, of which 4 showed epithelial microcystic edema. Eleven-year progression data reveal a marked increase in subepithelial corneal edema and gradual, profound increase in anterior corneal astigmatism. Sequencing of genomic DNA from the unrelated individual predictably identified a c.1349T>G [p.(Leu450Trp)] heterozygous variation in COL8A2. Confocal microscopy confirmed attenuated endothelium, and histopathology revealed no guttae, consistent with findings from a previously identified family. CONCLUSIONS: Peripheral, anterior microcystic corneal edema represents a characteristic aspect of the phenotype associated with the p.(Leu450Trp) substitution in COL8A2, in at least 2 of 3 known affected families worldwide. We describe long-term progression and Descemet stripping endothelial keratoplasty for this disease for the first time. PMID- 26989953 TI - Evaluation of Tear Meniscus Dynamics Using Anterior Segment Swept-Source Optical Coherence Tomography After Topical Solution Instillation for Dry Eye. AB - PURPOSE: To investigate tear meniscus dynamics using anterior segment swept source optical coherence tomography (SS-OCT) after the instillation of topical solutions for dry eye. DESIGN: Prospective, observational, cross-sectional study. METHODS: Thirty-six healthy subjects (28 men and 8 women; mean age, 34.4 +/- 6.7 years) were enrolled in this study. The lower tear meniscus height, tear meniscus area, and tear meniscus volume were assessed using anterior SS-OCT. After baseline measurements, 40 MUL of 0.1% sodium hyaluronate, 0.3% sodium hyaluronate, 3% diquafosol ophthalmic solution, or 2% rebamipide ophthalmic solution was instilled in one eye of 10 subjects each, whereas 40 MUL saline was instilled in the other eye. Tear meniscus measurements were obtained using SS-OCT at 30 seconds and 1, 3, 5, 10, 15, 20, and 30 minutes after instillation. RESULTS: The tear meniscus measurements showed a significant increase until 1, 3, 10, 10, and 3 minutes after the instillation of saline, 0.1% sodium hyaluronate, 0.3% sodium hyaluronate, 3% diquafosol, and 2% rebamipide, respectively, compared with the baseline levels (P < 0.05). Compared with those after saline instillation, the tear meniscus measurements were significantly higher until 30 seconds and 3, 30, and 15 minutes after the instillation of 0.1% sodium hyaluronate, 0.3% sodium hyaluronate, 3% diquafosol, and 2% rebamipide, respectively (P < 0.05). CONCLUSIONS: The instillation of ophthalmic solutions for the treatment of dry eye greatly increased tear meniscus measurements in healthy subjects. Thus, SS-OCT can be a practical tool for the quantitative evaluation of early-phase tear fluid dynamics. PMID- 26989954 TI - Tenons Patch Graft in the Management of Large Corneal Perforations. AB - PURPOSE: To describe a technique to manage corneal perforations between 3 and 6 mm in size using autologous Tenons tissue with cyanoacrylate glue and a bandage contact lens. METHODS: A thin layer of Tenons capsule harvested from the patient's own eye is used to seal the perforation and act as a scaffold. The Tenons patch graft is spread over the perforation and held in place by the application of cyanoacrylate glue. A bandage contact lens is then placed on the eye. RESULTS: A 6-year retrospective review of 28 patients who underwent this procedure was performed. One patient was lost to follow-up. Of the 27 patients who were followed up, 20 healed completely, with an adherent leucoma and preservation of the anterior chamber. The condition of one patient (with a perforated Pseudomonas corneal ulcer) progressively worsened despite maximum medical therapy and had to undergo evisceration. CONCLUSIONS: This procedure makes use of easily available autologous Tenons tissue in patients with corneal perforations too large to be managed with cyanoacrylate glue alone, to preserve eyeball morphology. A corneal transplant can then be done when the cornea has healed. PMID- 26989955 TI - Update on Acanthamoeba Keratitis: Diagnosis, Treatment, and Outcomes. AB - PURPOSES: A literature review to describe the current diagnosis and management of Acanthamoeba keratitis. RESULTS: Acanthamoeba is a ubiquitous protozoan: 8 species, 5 genotypic classes have been reported to cause keratitis. It is potentially a sight-threatening infection, and there is often a poor prognosis because of a significant delay in diagnosis and frequently a lack of effective medical management. Main risk factors are contact lens wear, poor hygiene, and contact with contaminated water. Current methods of diagnosis include corneal scrapings for histopathologic analysis, tissue culture, confocal microscopy, and polymerase chain reaction (PCR), each are reviewed in turn. Treatment options include medical (biguanides, diamidines, and corticosteroids) and surgical (epithelial debridement, amniotic membrane transplant, and penetrating keratoplasty). CONCLUSIONS: Early diagnosis and treatment are required to effectively manage this condition. PMID- 26989956 TI - Corneal Reinnervation and Sensation Recovery in Patients With Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves. AB - PURPOSE: To study corneal reinnervation and sensation recovery in Herpes zoster ophthalmicus (HZO). METHODS: Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis type 1 was implanted, and the explanted corneal tissues were examined by immunofluorescence histochemistry for betaIII-tubulin to stain for corneal nerves. RESULTS: The initial central corneal IVCM performed in each patient showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later before undergoing surgery, case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, case 2 showed regeneration of the central subbasal nerves (4786 MUm/mm) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in case 1 showed no corneal nerves, whereas case 2 showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the Boston keratoprosthesis in both patients to study innervation of the corneal transplant. Case 1 showed no nerves, whereas case 2 showed new nerves growing from the periphery into the corneal graft. CONCLUSIONS: We demonstrate that regaining corneal innervation and corneal function are possible in patients with HZO as shown by corneal sensation, IVCM, and ex vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time. PMID- 26989957 TI - Clinical Features, Antibiotic Susceptibility Profiles, and Outcomes of Infectious Keratitis Caused by Achromobacter xylosoxidans. AB - PURPOSE: Reports on Achromobacter xylosoxidans ocular infections are increasing, drawing attention to its emerging role in infectious keratitis. The purpose of this study is to report the clinical features, antibiotic sensitivities, and visual outcomes of infectious keratitis secondary to Achromobacter xylosoxidans. METHODS: A microbiology database and clinical chart review was performed in all patients diagnosed with A. xylosoxidans keratitis at the Bascom Palmer Eye Institute between the years 1987 and 2014. Initial presentation, antimicrobial susceptibilities, minimum inhibitory concentrations (MICs), treatment course, and outcomes were recorded. RESULTS: Twenty-eight patients were identified. The main risk factors were corneal graft (n = 8, 28.6%) and contact lens wear (n = 8, 28.6%). On presentation, visual acuity was 20/100 or worse in 20 (71.2%) patients. Hypopyon was present in 7 (25.0%) patients. In most cases, topical fluoroquinolones or tobramycin were the initial treatment, often accompanied by vancomycin. High susceptibility rates were found for piperacillin [100%, minimum inhibitory concentration for 90% of isolates (MIC90) = 8] and ticarcillin (100%, MIC90 = 16). Low susceptibility rates were documented for ciprofloxacin (46.7%, MIC90 = 8), tobramycin (26.7%, MIC90 = 16), and gentamicin (20%, MIC90 = 16). One (3.6%) patient suffered endophthalmitis. Six (21.4%) patients underwent therapeutic penetrating keratoplasty, and 2 (7.1%) patients had conjunctival flap surgery. Visual acuity at final follow-up was 20/100 or worse in 16 (57.1%) patients. CONCLUSIONS: Infectious keratitis caused by A. xylosoxidans is associated with poor visual outcomes. Fluoroquinolones and aminoglycosides are not appropriate treatments for these ocular infections. Further studies are needed to define the clinical application of compound piperacillin and ticarcillin eye drops. PMID- 26989959 TI - Dr John Nottingham's 1854 Landmark Treatise on Conical Cornea Considered in the Context of the Current Knowledge of Keratoconus. AB - John Nottingham has been widely credited with the first accurate description of keratoconus in his treatise on conical cornea, published in 1854. Contained within the 270-page treatise are accounts and theories of keratoconus postulated by authors such as Scarpa, von Carion, von Ammon, and Mackenzie, synthesized by Nottingham in a treatise containing his own original observations. Nottingham's work delves deeply into keratoconus, with coverage reminiscent of a modern review, albeit in a far less succinct manner. He extensively describes the epidemiology, clinical presentation, underlying cause, and treatment of keratoconus. However, the concepts put forth are limited largely by the contemporary lack of understanding of the underlying anatomy and physiology of the eye, and the observations, by technological limitations. He postulates a similar treatment algorithm to that used today; optical devices being the management option of choice in the mild stages with surgery being a last resort. None of the surgical methods discussed are used in the modern era, but he does make reference to the possible efficacy of corneal transplantation. Nottingham's treatise was published over 160 years ago, yet his ideas and observations are surprisingly accurate. It is very possible that he was the first person to publish an accurate, comprehensive description of keratoconus. PMID- 26989958 TI - Corneal Cross-Linking: Evaluating the Potential for a Lower Power, Shorter Duration Treatment. AB - PURPOSE: To determine the cross-linking effect of a riboflavin ultraviolet-A (UV A) corneal cross-linking treatment that is both shorter and has lower energy than the Dresden protocol. METHODS: In a first experiment, 12 human corneas were presoaked with riboflavin and then irradiated with UV-A at 3 mW/cm after clearing the surface of riboflavin, with no added riboflavin during irradiation. Percent UV-A transmission through the corneas was measured at intervals up to 30 minutes. A second experiment involved 24 porcine corneas. Eight were de-epithelialized, presoaked in riboflavin for 30 minutes, and irradiated at 1.5 mW/cm for 10 minutes. An additional 8 were riboflavin treated and similarly irradiated, but with epithelium intact and a final 8 corneas were not treated. Young modulus was measured in all 24 corneas at the end of the experiment. RESULTS: The first experiment showed essentially complete riboflavin oxidation after only 10 minutes. Based on these results, a shortened UV-A exposure cross-linking experiment was designed using a reduced UV-A fluence of 1.5 mW/cm, an endothelial exposure within safety limits in humans. With this protocol Young modulus was the same in the irradiated porcine corneas but with epithelium intact as in the untreated corneas. In contrast, Young modulus increased by a factor of 1.99 in the UV-A cross-linked corneas at 1.5 mW/cm for 10 minutes with the epithelium removed. CONCLUSIONS: A shorter, lower energy protocol than the Dresden protocol seems to provide a significant increase in Young modulus, similar to published results with higher energy, longer exposure protocols. PMID- 26989960 TI - Visual Outcomes of Repeat Versus Primary Descemet Stripping Automated Endothelial Keratoplasty-A Paired Comparison. AB - PURPOSE: To compare the results of repeat Descemet stripping automated endothelial keratoplasty (DSAEK) with those of primary DSAEK. MATERIALS AND METHODS: This retrospective study consisted of all consecutive eyes that underwent one or more repeat DSAEK surgeries after primary DSAEK performed at Villa Serena-Villa Igea Private Hospitals (Forli, Italy) between January 2005 and June 2015. A paired comparison between the outcomes of primary and the second DSAEK was performed. Main outcome measures included best recorded best spectacle corrected visual acuity (BSCVA), postoperative endothelial cell loss (ECL), and refractive error. RESULTS: Of 1413 procedures, 51 eyes were included in the final analysis. Indications for primary DSAEK included pseudophakic bullous keratopathy (n = 21), Fuchs endothelial dystrophy (n = 20), failed penetrating keratoplasty (n = 9), and trauma (n = 1). Indications for repeat DSAEK were slowly progressive ECL (n = 35), endothelial rejection (n = 15), and host-graft interface abnormalities (n = 1). Preoperative BSCVA (logarithm of the minimum angle of resolution 1.23 +/- 0.8 vs. 1.38 +/- 0.6, P = 0.29) and best postoperative BSCVA (logarithm of the minimum angle of resolution 0.32 +/- 0.44 vs. 0.34 +/- 0.49, P = 0.70) did not differ significantly between the 2 groups. ECLs for primary and repeat DSAEK at 1 (46% +/- 16% vs. 40% +/- 18%, P = 0.22) and 2 years (50% +/- 18% vs. 44% +/- 2%, P = 0.33) were also similar. The mean postoperative spherical equivalent did not differ significantly between the 2 groups (-0.01 +/- 1.9 vs. 0.5 +/- 1.6, P = 0.08) nor did the absolute astigmatic error (1.6 +/- 1 vs. 1.8 +/- 1.2, respectively, P = 0.17). CONCLUSIONS: After the failure of a primary DSAEK graft, a subsequent DSAEK can yield visual outcomes and ECL rates that are comparable with those of primary DSAEK. PMID- 26989961 TI - Development of Herpes Simplex Virus Infectious Epithelial Keratitis During Oral Acyclovir Therapy and Response to Topical Antivirals. AB - PURPOSE: To describe 3 cases of herpes simplex virus (HSV) vesicular blepharitis that progressed to infectious epithelial keratitis despite treatment with oral acyclovir, but responded to topical antiviral therapy. METHODS: Retrospective review of a small case series. RESULTS: One adult and 2 children presented with unilateral HSV vesicular blepharitis without evidence of corneal involvement. Each patient was placed on a therapeutic dose of oral acyclovir. While taking oral antiviral therapy, the patients developed HSV infectious epithelial keratitis, which was treated with trifluridine 1% solution 9 times daily in the adult and ganciclovir 0.15% ophthalmic gel 5 times daily in the 2 children. All 3 cases showed resolution of epithelial keratitis within 3 to 10 days after initiation of topical antiviral treatment while oral acyclovir was continued. CONCLUSIONS: Oral antiviral therapy alone may not adequately prevent progression of infectious ocular HSV blepharoconjunctivitis. Topical antiviral therapy appeared to enable resolution of HSV epithelial keratitis that arose during oral acyclovir treatment. PMID- 26989962 TI - How Abnormal Is the Noncorneal Biometry of Keratoconic Eyes? AB - PURPOSE: To determine whether the noncorneal biometry in keratoconic eyes deviates from that in healthy eyes. METHODS: The right eyes of 200 healthy subjects and 76 patients with keratoconus were measured with an autorefractometer, a Scheimpflug tomographer, and an optical biometer. The analysis consisted of a general linear model (GLM), correcting for age and gender effects, comparing keratoconic eyes with healthy eyes, and emmetropic eyes. Next, 20 patients with mild keratoconus in one eye and moderate keratoconus in the fellow eye were analyzed to assess the effect of disease stage. RESULTS: As expected the keratoconic group differed significantly from both the healthy and the emmetropic groups for most refractive, corneal, and anterior chamber parameters (GLM, P < 0.001). For the vitreous depth V and the axial length L, the keratoconic group showed significantly larger values than the emmetropic group (V: +0.68 +/- 0.19 mm, P = 0.001; L: +0.63 +/- 0.14 mm, P < 0.001), but not larger than the healthy group (V: +0.18 +/- 0.20 mm, P = 0.364; L: +0.09 +/- 0.14 mm, P = 0.519). Besides the corneal parameters, the stage of the disease led to a significantly deeper aqueous depth (+0.07 +/- 0.02 mm; Wilcoxon signed rank, P = 0.002), but no significant difference in axial length (P = 0.940). CONCLUSIONS: Current analysis does not confirm the previously suggested association between keratoconus and higher amounts of axial myopia, which may have been the result of selection bias by using emmetropic eyes as a healthy control group. PMID- 26989963 TI - A new beginning. PMID- 26989964 TI - Is mental illness migratory? PMID- 26989965 TI - Mirtazapine: only for depression? AB - BACKGROUND: Mirtazapine is an antidepressant first approved in the Netherlands in 1994 for the treatment of major depressive disorder. However, evidence suggests its effectiveness in a variety of other psychiatric disorders and non-psychiatric medical conditions. OBJECTIVE: The present paper reviews the published literature on the off-label indications of Mirtazapine. METHODS: A search of the relevant literature from MEDLINE, PsycLIT and EMBASE databases, included in the Science Citation Index and available up to March 2006, was conducted using the terms mirtazapine, case-reports, open-label trials and randomized controlled trials. Only articles referring to conditions other than major depression were included in this present review. RESULTS: Off-label use of mirtazapine has been reported in panic disorder, post-traumatic stress disorder, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, dysthymia, menopausal depression, poststroke depression, depression as a result of infection with human immunodeficiency virus, elderly depression, Methylenedioxymethamphetamine (MDMA) induced depression, hot flashes, alcohol and other substance use disorders, sleep disorders, sexual disorders, tension-type headaches, cancer pain, fibromyalgia, schizophrenia and other less frequent conditions. CONCLUSIONS: So far, data on the off-label usefulness of mirtazapine are limited and mainly based on observations from case reports or open-label studies. However, positive cues suggest that confirmation of these preliminary data with randomized controlled trials may give sufficient evidence to warrant the use of mirtazapine in a broad range of disorders. PMID- 26989966 TI - Neural mechanisms of the cognitive control of emotion. AB - BACKGROUND: Emotion regulation involves the initiation of new emotional responses and continual alteration of current emotions in response to rapidly changing environmental and social stimuli. The capacity to effectively implement emotion regulation strategies is essential for psychological health; impairments in the ability to regulate emotions may be critical to the development of clinical levels of depression, anxiety and mania. OBJECTIVE: This review provides a summary of findings from current research examining the neural mechanisms of emotion regulation by means of conscious cognitive strategies of reappraisal. These findings are considered in the context of related concepts of emotion perception and emotion generation, with discussion of the likely cognitive neuropsychological contributions to emotion regulation and the implications for psychiatric disorders. RESULTS: Convergent evidence implicates an inhibitory role of prefrontal cortex and cingulate regions upon subcortical and cortical emotion generation systems in the cognitive control of emotional experience. Concurrent modulation of cortical activity by the peripheral nervous system is highlighted by recent studies using simultaneous physiological and neuroimaging techniques. Individual differences in emotion perception, generation of affect and neuropsychological skills are likely to have direct consequences for emotion regulation. CONCLUSIONS: Emotion regulation relies on synergy within brain stem, limbic and cortical processes that promote the adaptive perception, generation and regulation of affect. Aberrant emotion processing in any of these stages may disrupt this self-sustaining regulatory system, with the potential to manifest in distinct forms of emotion dysregulation as seen in major psychiatric disorders such as depression, bipolar disorder and schizophrenia. PMID- 26989967 TI - Seasonal influences on first-episode admission in affective and non-affective psychosis. AB - BACKGROUND: Since bipolar affective disorder has been recorded, clinicians treating patients with this disorder have noted the cyclic nature of episodes, particularly an increase in mania in the spring and summer months and depression during winter. OBJECTIVE: The aim of this study was to investigate seasonality in symptom onset and service admissions over a period of 10 years in a group of patients (n= 359) with first-episode (FE) mania (n= 133), FE schizoaffective disorder (n= 49) and FE schizophrenia (n= 177). METHOD: Patients were recruited if they were between 15 and 28 years of age and if they resided in the geographical mental health service catchment area. The number of patients experiencing symptom onset and service admission over each month and season was recorded. RESULTS: In terms of seasonality of time of service admission, the results indicate a high overall seasonality (particularly in men), which was observed in both the schizoaffective and the bipolar groups. In terms of seasonality of symptom onset, the results indicate that seasonality remains in the male bipolar group, but other groups have no seasonal trend. CONCLUSIONS: This provides further evidence that systems mediating the entrainment of biological rhythms to the environment may be more pronounced in BPAD than in schizoaffective disorder and schizophrenia. These results may help facilitate the preparedness of mental heath services for patients at different times of the year. PMID- 26989968 TI - Neuropsychological function in bulimia with comorbid borderline personality disorder and depression. AB - BACKGROUND: In bulimia nervosa (BN), borderline personality disorder (BPD) and major depression (MDD) are frequently comorbid conditions. Executive function has been found to be impaired in BPD and MDD, but the impact of comorbidity on neuropsychological function has rarely been investigated. OBJECTIVE: To investigate neuropsychological function in BN with a focus on comorbid BPD and MDD. METHODS: One hundred forty-four medication-free female patients entering a study of psychological treatments for BN performed a brief battery of neuropsychological tests. Comorbid MDD and BPD were systematically identified using standard interviews. Neuropsychological test results were compared. RESULTS: Forty-one subjects had comorbid BPD and 35 had comorbid MDD, while 15 had both. There was no effect of comorbid MDD, but there was a significant effect of BPD and a significant interaction between the diagnosis of MDD and BPD on executive tasks (trail making and Stroop). Thus, compared with subjects without BPD, subjects with BPD performed significantly worse on tests of executive function, while the group with both comorbidities performed even worse. CONCLUSIONS: There appears to be an additive effect of BPD and MDD resulting in impaired executive neuropsychological function. Future studies on either disorder and on BN should examine and account for the effect of comorbidity. PMID- 26989969 TI - Anesthesia for patients with pantothenate-kinase-associated neurodegeneration (Hallervorden-Spatz disease) - a literature review. AB - BACKGROUND: Hallervorden-Spatz disease (HSD) is a rare, progressive neurodegenerative disorder; the new and preferred name for HSD is 'pantothenate kinase-associated neurodegeneration' (PKAN). Other suggested names are 'neurodegeneration with brain iron accumulation type 1' or 'infantile neuroaxonal dystrophy'. Patients with PKAN have many complications, which lead to numerous anesthetic management challenges. Reports concerning the anesthetic management of patients with PKAN are very limited. OBJECTIVE: To determine the anesthetic management and techniques as well as relevant complications for patients with PKAN. METHODS: In this study, we review previously published literature regarding the anesthesia-relevant clinical symptoms, the anesthetic management and techniques, and possible complications for this disorder. RESULTS: Only four studies describing the anesthetic management and anesthetic techniques in patients with PKAN were found. Anesthesia-relevant symptoms influence the preanesthetic management (eg difficulties in articulation, dementia), the induction of anesthesia (eg oromandibular rigidity, seizures, dysphagia, aspiration) and the postoperative care (eg respiratory disability). CONCLUSION: Reports concerning the anesthetic management of patients with PKAN are very limited, possibly as a result of the rareness of the disorder. Like many other patients with neurodegenerative diseases, patients with PKAN have many anesthesia relevant symptoms, leading to numerous anesthetic management challenges. In general, the anesthetic complications associated with PKAN are usually no different from those associated with other neurodegenerative diseases, and the management of these are usually concordant. PMID- 26989970 TI - Comparing running therapy with physiotraining therapy in the treatment of mood disorders. AB - BACKGROUND: Despite various studies, supportive evidence for the efficacy of exercise in treatment of mental illness is still weak. OBJECTIVE: The aim of this study was to compare two forms of exercise, namely running therapy (RT) and physiotraining therapy (PT), on stationary devices. METHODS: Patients in a day treatment programme for treatment of affective disorders were randomly allocated to one of the exercise groups or to a control group. Depression scores, self efficacy, physical conditions and appreciations of the training programme were measured. RESULTS: After 6 weeks, no significant differences were found between both the training groups and the control group; however, after 12 weeks, the physiotraining group showed significant improvement on scores for blind-rated Hamilton Rating Scale for Depression and on scores for self-rated Beck Depression Inventory 21-item version. CONCLUSIONS: Our results suggest that PT has advantages over RT. We speculate that an improved feeling of self-efficacy may be a mediating factor. PMID- 26989971 TI - No borna disease virus-specific RNA detected in blood of race horses and jockeys. AB - BACKGROUND: Borna disease virus (BDV) predominantly infects horses and sheep, causing a broad range of behavioural disorders. It is controversial whether BDV infects humans and causes psychiatric disorders. OBJECTIVES: We searched for BDV derived nucleic acids in blood of race horses and jockeys riding the horses. METHODS: We assayed for the BDV genome in RNA extracted from peripheral blood mononuclear cells (PBMC) of 39 race horses and 48 jockeys. Two polymerase chain reaction protocols [one-tube reverse transcription-polymerase chain reaction (RT PCR) and two-step RT-PCR] were used to assay BDV p24 and p40 transcripts. RESULTS: The p24 and p40 viral nucleic acid sequences were not detected in the PBMC RNAs from any of the race horses or jockeys. CONCLUSIONS: These data do not support an epidemiological association between BDV infection, race horses and humans. PMID- 26989972 TI - Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner. AB - Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5* folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5* folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5* the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation. PMID- 26989973 TI - Open Versus Laparoscopic Management of Incisional Abdominal Hernia: Cohort Study Comparing Quality of Life Outcomes. AB - BACKGROUND AND AIMS: Incisional hernia is a common complication of laparotomy. The long-term effectiveness of the laparoscopic repair compared to the open approach remains to be proven. We investigated the 1-year impact of open and laparoscopic repair of incisional hernia on quality of life outcomes. METHODS: Single-center cohort study. The clinical data of patients who underwent open or laparoscopic surgery for primary midline incisional hernia were retrieved from hospital records and from a research database. Criteria of exclusion were emergency procedures, associated bowel resection, and recurrent incisional hernia. Complications and recurrence rates were analyzed. The visual analog scale (VAS) and the Short-Form 36 (SF-36) were used to assess pain and quality of life 1 year after surgery in patients free of recurrence. RESULTS: One hundred twenty four patients were eligible for inclusion in the study. The mean follow-up was 3 +/- 2 years (interquartile range [IQR] 2.0). Overall, 9% of patients in the open group and 7% in the laparoscopic group presented with hernia recurrence (P = .685). Sixty-six of the 124 patients, who were operated between 2009 and 2014 by the same surgical team with expertise in advanced laparoscopic surgery, were considered for the study. Nine (14%) of these patients were lost to follow-up and three (5%) had a recurrent hernia, reducing the final sample size to 54 patients of whom 26 operated through an open approach and 28 through laparoscopy. The two groups were comparable according to demographic variables, comorbidity, and postoperative morbidity. The laparoscopic approach required less operative time (<.001) and length of hospital stay (P = .002). The VAS and the SF-36 scores were similar in the 54 patients, 26 in the open group and 28 in the laparoscopic group, who completed the 1-year assessment. CONCLUSIONS: Health-related quality of life at 1 year was similar in patients undergoing open or laparoscopic repair of incisional abdominal hernia. PMID- 26989974 TI - Inadequacy of 3-month Oswestry Disability Index outcome for assessing individual longer-term patient experience after lumbar spine surgery. AB - OBJECTIVE Prospective longitudinal outcomes registries are at the center of evidence-driven health care reform. Obtaining real-world outcomes data at 12 months can be costly and challenging. In the present study, the authors analyzed whether 3-month outcome measurements sufficiently represent 12-month outcomes for patients with degenerative lumbar disease undergoing surgery. METHODS Data from 3073 patients undergoing elective spine surgery for degenerative lumbar disease were entered into a prospective multicenter registry (N(2)QOD). Baseline, 3 month, and 12-month follow-up Oswestry Disability Index (ODI) scores were recorded. The absolute differences between actual 12- and 3-month ODI scores was evaluated. Additionally, the authors analyzed the absolute difference between actual 12-month ODI scores and a model-predicted 12-month ODI score (the model used patients' baseline characteristics and actual 3-month scores). The minimal clinically important difference (MCID) for ODI of 12.8 points and the substantial clinical benefit (SCB) for ODI of 18.8 points were used based on the previously published values. The concordance rate of achieving MCID and SCB for ODI at 3-and 12-months was computed. RESULTS The 3-month ODI scores differed from 12-month scores by an absolute difference of 11.9 +/- 10.8, and predictive modeling estimations of 12-month ODI scores differed from actual 12-month scores by a mean (+/- SD) of 10.7 +/- 9.0 points (p = 0.001). Sixty-four percent of patients (n = 1982) achieved an MCID for ODI at 3 months in comparison with 67% of patients (n = 2088) by 12 months; 51% (n = 1731) and 61% (n = 1860) of patients achieved SCB for ODI at 3 months and 12 months, respectively. Almost 20% of patients had ODI scores that varied at least 20 points (the point span of an ODI functional category) between actual 3- and 12-month values. In the aggregate analysis of achieving MCID, 77% of patients were concordant and 23% were discordant in achieving or not achieving MCID at 3 and 12 months. The discordance rates of achieving or not achieving MCID for ODI were in the range of 19% to 27% for all diagnoses and treatments (decompression with and without fusion). The positive and negative predictive value of 3-months ODI to predict 12-month ODI was 86% and 60% for MCID and 82% and 67% for SCB. CONCLUSIONS Based on their findings, the authors conclude the following: 1) Predictive methods for functional outcome based on early patient experience (i.e., baseline and/or 3-month data) should be used to help evaluate the effectiveness of procedures in patient populations, rather than serving as a proxy for long-term individual patient experience. 2) Prospective longitudinal registries need to span at least 12 months to determine the effectiveness of spine care at the individual patient and practitioner level. PMID- 26989975 TI - How well do subjective Hospital Compare metrics reflect objective outcomes in spine surgery? AB - OBJECTIVE The accuracy of public reporting in health care is an issue of debate. The authors investigated the association of patient satisfaction measures from a public reporting platform with objective outcomes for patients undergoing spine surgery. METHODS The authors performed a cohort study involving patients undergoing elective spine surgery from 2009 to 2013 who were registered in the New York Statewide Planning and Research Cooperative System database. This cohort was merged with publicly available data from the Centers for Medicare and Medicaid Services (CMS) Hospital Compare website. A mixed-effects regression analysis, controlling for clustering at the hospital level, was used to investigate the association of patient satisfaction metrics with outcomes. RESULTS During the study period, 160,235 patients underwent spine surgery. Using a mixed-effects multivariable regression analysis, the authors demonstrated that undergoing elective spine surgery in hospitals with a higher percentage of patient-assigned high satisfaction scores was not associated with a decreased rate of discharge to rehabilitation (OR 0.77, 95% CI 0.57-1.06), mortality (OR 0.96, 95% CI 0.90-1.01), or hospitalization charges (beta 0.04, 95% CI -0.16 to 0.23). However, it was associated with decreased length of stay (LOS; beta -0.19, 95% CI -0.33 to -0.05). Similar associations were identified for hospitals with a higher percentage of patients who claimed they would recommend these institutions to others. CONCLUSIONS Merging a comprehensive all-payer cohort of spine surgery patients in New York state with data from the CMS Hospital Compare website, the authors were not able to demonstrate an association of improved performance in patient satisfaction measures with decreased mortality, rate of discharge to rehabilitation, and hospitalization charges. Increased patient satisfaction was associated with decreased LOS. PMID- 26989976 TI - Evaluating the effects of recombinant human bone morphogenetic protein-2 on pain associated behaviors in a rat model following implantation near the sciatic nerve. AB - OBJECTIVE It has been hypothesized that the recombinant human bone morphogenetic protein-2 (rhBMP-2) amplification of the host inflammatory response interacts with nerves in the spine and contributes to the occurrence of new, postoperative complaints of radiculitis. This in vivo rat study was conducted to assess the capacity for rhBMP-2/ACS (rhBMP-2 applied to absorbable collagen sponge [ACS]) to stimulate pain-associated behaviors in the rat chronic constriction injury (CCI) model. METHODS Rats were randomly assigned to one of 14 treatment groups. Half of the animals underwent a sham procedure in which the left sciatic nerve was exposed and manipulated but no ligature was placed (Sham cohort), while the remaining animals had chromic gut sutures tied around the sciatic nerve to induce CCI (CCI cohort). The following test articles were applied to the sciatic nerve in each cohort: saline alone, saline applied to ACS, 0.1 mg/ml rhBMP-2 applied to ACS, or 1.0 mg/ml rhBMP-2 applied to ACS. The ACS was either wrapped around the sciatic nerve or implanted adjacent to the nerve. Thermal withdrawal latency was assessed on Days 7, 14, 21, and 28 postoperatively. Isolated nerves from selected rats in each group were examined and assessed for histopathological changes on Days 3, 7, 14, and 28. RESULTS CCI produced a significant pain behavioral response for all treatment groups at all time points. In the Sham cohort, 0.1 mg/ml rhBMP-2/ACS wrapped around the nerve (WRP) decreased thermal withdrawal on Day 28, and 1.0 mg/ml rhBMP-2/ACS placed adjacent to the nerve (ADJ) decreased thermal withdrawal on Days 21 and 28. Conversely, in the CCI cohort, 0.1 mg/ml rhBMP-2/ACS ADJ increased thermal withdrawal latencies on Day 7; 1.0 mg/ml rhBMP 2/ACS ADJ increased thermal withdrawal latencies on Day 7; and 1.0 mg/ml rhBMP 2/ACS WRP increased thermal withdrawal on Days 7 and 14. Histologically, the effect of rhBMP-2 on nerve inflammation was unclear, as inflammatory cell infiltration was similar in the rhBMP-2/ACS and saline/ACS groups. rhBMP-2 was variably associated with bone formation within the epineurium at 14 days, and more prevalently at 28 days, with no clear relationship between dose or ACS positioning. CONCLUSIONS In this study, rhBMP-2/ACS did not appear to induce pain independent of grossly visible ectopic bone formation. At the earliest time points, rhBMP-2 appeared to have a neuroprotective effect as evidenced by decreased pain exhibited by the rhBMP-2-treated animals in the CCI cohort, but this effect diminished over time, and by Day 28, the pain behavioral responses in the rhBMP-2-treated group were comparable to those in the group in which saline was applied to the nerve. In the Sham cohort, there was a dose-independent induction of pain at later time points, presumably due to new bone formation mechanically irritating the nerve. Histological examination revealed nerve lesions that appeared to be caused by mechanical trauma associated with surgical manipulation of the nerve during placement of the ACS and/or CCI sutures. PMID- 26989977 TI - How to predict return to work after lumbar discectomy: answers from the NeuroPoint-SD registry. AB - OBJECTIVE To date, the factors that predict whether a patient returns to work after lumbar discectomy are poorly understood. Information on postoperative work status is important in analyzing the cost-effectiveness of the procedure. METHODS An observational prospective cohort study was completed at 13 academic and community sites (NeuroPoint-Spinal Disorders [NeuroPoint-SD] registry). Patients undergoing single-level lumbar discectomy were included. Variables assessed included age, sex, body mass index (BMI), SF-36 physical function score, Oswestry Disability Index (ODI) score, presence of diabetes, smoking status, systemic illness, workers' compensation status, and preoperative work status. The primary outcome was working status within 3 months after surgery. Stepwise logistic regression analysis was performed to determine which factors were predictive of return to work at 3 months following discectomy. RESULTS There were 127 patients (of 148 total) with data collected 3 months postoperatively. The patients' average age at the time of surgery was 46 +/- 1 years, and 66.9% of patients were working 3 months postoperatively. Statistical analyses demonstrated that the patients more likely to return to work were those of younger age (44.5 years vs 50.5 years, p = 0.008), males (55.3% vs 28.6%, p = 0.005), those with higher preoperative SF-36 physical function scores (44.0 vs 30.3, p = 0.002), those with lower preoperative ODI scores (43.8 vs 52.6, p = 0.01), nonsmokers (83.5% vs 66.7%, p = 0.03), and those who were working preoperatively (91.8% vs 26.2%, p < 0.0001). When controlling for patients who were working preoperatively (105 patients), only age was a statistically significant predictor of postoperative return to work (44.1 years vs 51.1 years, p = 0.049). CONCLUSIONS In this cohort of lumbar discectomy patients, preoperative working status was the strongest predictor of postoperative working status 3 months after surgery. Younger age was also a predictor. Factors not influencing return to work in the logistic regression analysis included sex, BMI, SF-36 physical function score, ODI score, presence of diabetes, smoking status, and systemic illness. Clinical trial registration no.: 01220921 ( clinicaltrials.gov ). PMID- 26989979 TI - An alternative approach for zeta-factor measurement using pure element nanoparticles. AB - It is very challenging to measure the chemical composition of hetero nanostructures in a reliable and quantitative manner. Here, we propose a novel and straightforward approach that can be used to quantify energy dispersive X-ray spectra acquired in a transmission electron microscope. Our method is based on a combination of electron tomography and the so-called zeta-factor technique. We will demonstrate the reliability of our approach as well as its applicability by investigating Au-Ag and Au-Pt hetero nanostructures. Given its simplicity, we expect that the method could become a new standard in the field of chemical characterization using electron microscopy. PMID- 26989978 TI - Hospital charges associated with "never events": comparison of anterior cervical discectomy and fusion, posterior lumbar interbody fusion, and lumbar laminectomy to total joint arthroplasty. AB - OBJECTIVE Beginning in 2008, the Centers for Medicare and Medicaid Service (CMS) determined that certain hospital-acquired adverse events such as surgical site infection (SSI) following spine surgery should never occur. The following year, they expanded the ruling to include deep vein thrombosis (DVT) and pulmonary embolism (PE) following total joint arthroplasty. Due to their ruling that "never events" are not the payers' responsibility, CMS insists that the costs of managing these complications be borne by hospitals and health care providers, rather than billings to health care payers for additional care required in their management. Data comparing the expected costs of such adverse events in patients undergoing spine and orthopedic surgery have not previously been reported. METHODS The California State Inpatient Database (CA-SID) from 2008 to 2009 was used for the analysis. All patients with primary procedure codes indicating anterior cervical discectomy and fusion (ACDF), posterior lumbar interbody fusion (PLIF), lumbar laminectomy (LL), total knee replacement (TKR), and total hip replacement (THR) were analyzed. Patients with diagnostic and/or treatment codes for DVT, PE, and SSI were separated from patients without these complication codes. Patients with more than 1 primary procedure code or more than 1 complication code were excluded. Median charges for treatment from primary surgery through 3 months postoperatively were calculated. RESULTS The incidence of the examined adverse events was lowest for ACDF (0.6% DVT, 0.1% PE, and 0.03% SSI) and highest for TKA (1.3% DVT, 0.3% PE, 0.6% SSI). Median inpatient charges for uncomplicated LL was $51,817, compared with $73,432 for ACDF, $143,601 for PLIF, $74,459 for THR, and $70,116 for TKR. Charges for patients with DVT ranged from $108,387 for TKR (1.5 times greater than index) to $313,536 for ACDF (4.3 times greater than index). Charges for patients with PE ranged from $127,958 for TKR (1.8 times greater than index) to $246,637 for PLIF (1.7 times greater than index). Charges for patients with SSI ranged from $168,964 for TKR (2.4 times greater than index) to $385,753 for PLIF (2.7 times greater than index). CONCLUSIONS Although incidence rates are low, adverse events of spinal procedures substantially increase the cost of care. Charges for patients experiencing DVT, PE, and SSI increased in this study by factors ranging from 1.8 to 4.3 times those for patients without such complications across 5 common spinal and orthopedic procedures. Cost projections by health care providers will need to incorporate expected costs of added care for patients experiencing such complications, assuming that the cost burden of such events continues to shift from payers to providers. PMID- 26989980 TI - Exploring the complexities of body image experiences in middle age and older adult women within an exercise context: The simultaneous existence of negative and positive body images. AB - Despite many body changes that accompany the aging process, the extant research is limited on middle age and older adults' body image experiences. The purpose of the present study was to explore how body image is represented for middle age and older adult women. Using thematic analysis, 10 women over the age of 55 were interviewed within an exercise context. The following themes were found: body dissatisfaction, body satisfaction despite ageist stereotypes, neutral body image within cohort, and positive body image characteristics. Negative and positive body images were experienced simultaneously, with neutral experiences expressed as low levels of dissatisfaction. This supports the contention that negative and positive body images exist on separate continuums and neutral body image is likely on the same continuum as negative body image. Programs that foster a social support network to reduce negative body image and improve positive body image in older female populations are needed. PMID- 26989981 TI - The effect of natural organic matter on bioaccumulation and toxicity of chlorobenzenes to green algae. AB - The effect of natural organic matter (NOM) on toxicity and bioavailability of hydrophobic organic contaminants (HOCs) to aquatic organisms has been investigated with conflicting results and undefined mechanisms, and few studies have been conducted on volatile HOCs. In this study, six volatile chlorobenzenes (CBs) with 1-6 chlorine substitutions were investigated for their bioaccumulation in an acute toxicity to a green alga (Chlorella pyrenoidosa) in the presence/absence of Suwannee River NOM (SRNOM). The fluorescence quenching efficiency of SRNOM increased as the number of chlorine substitutions of CBs increased. SRNOM increased the cell-surface hydrophobicity of algae and decreased the release rates of algae-accumulated CBs, thus increasing the concentration factor (CF) and accumulation of the CBs in the algae. SRNOM increased the toxicity of monochlorobenzene and 1,2-dichlorobenzene, decreased the toxicity of pentachlorobenzene and hexachlorobenzene, and had no significant effect on the toxicity of 1,2,3-trichlorobenzene and 1,2,3,4-tetrachlorobenzene. Relationships between the 96 h CF/IC50 (i.e., the CB concentration leading to a 50% algal growth reduction compared with the control) and physicochemical properties of CBs with/without SRNOM were established, providing reasonable explanations for the experimental results. These findings will help with the accurate assessment of ecological risks of organic pollutants in the presence of NOM. PMID- 26989982 TI - Selective denitrification of flue gas by O3 and ethanol mixtures in a duct: Investigation of processes and mechanisms. AB - A novel selective denitrification process, referred as O3-ethanol oxidation method, was developed by injecting O3 and ethanol mixtures into the simulated flue gas duct. The organic radicals, generated through the ethanol oxidation by O3, can oxidize NO into NO2, and finally into important industrial raw, namely, nitrate organics or aqueous nitrate acids. The residual ethanol in the tail can be recycled. The CO3(2-), HCO3(-) and SO2 in the flue gas hardly exhibit any effect on the NOX removal. Compared to the conventional O3 oxidation method, the present method shows higher selective oxidation of NO, higher NO(X) removal and less O3 consumption as well as proves lower initial investment and operating costs with more compact equipment. PMID- 26989983 TI - Lipases and whole cell biotransformations of 2-hydroxy-2 (ethoxyphenylphosphinyl)acetic acid and its ester. AB - A wide spectrum of commercially available lipases and microbial whole cells catalysts were tested for biotransformations of 2-hydroxy-2 (ethoxyphenylphosphinyl)acetic acid 1 and its butyryl ester. The best results were achieved for biocatalytic hydrolysis of ester: 2-butyryloxy-2 (ethoxyphenylphosphinyl)acetic acid 2 performed by lipase from Candida cylindracea, what gave optically active products with 85% enantiomeric excess, 50% conversion degree and enantioselectivity 32.9 for one pair of enantiomers. Also enzymatic systems of Penicillium minioluteum and Fusarium oxysporum were able to hydrolyze tested compound with high enantiomeric excess (68-93% ee), enantioselectivity (44 for one pair of enantiomers) and conversion degree about 50-55%. Enzymatic acylation of hydroxyphosphinate was successful in case when porcine pancreas lipase was used. After 4days of biotransformation the conversion reaches 45% but the enantiomeric enrichment of the isomers mixture do not exceed 43%. Obtained chiral compounds are valuable derivatizing agents for spectroscopic (NMR) evaluation of enantiomeric excess for particular compounds (e.g. amino acids). PMID- 26989985 TI - New insights into the yin and yang of the endocannabinoid system in health and disease. AB - LINKED ARTICLES: This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc. PMID- 26989984 TI - Remobilization causes site-specific cyst formation in immobilization-induced knee cartilage degeneration in an immobilized rat model. AB - An understanding of the articular cartilage degenerative process is necessary for the prevention and treatment of joint disease. The present study aimed to examine how long-term immobilization-induced cartilage degeneration is aggravated by remobilization. Sixty 8-week-old male Wistar rats were used in this study. The unilateral knee joint was immobilized using an external fixator for 8 weeks. The rats were killed at 0 and 3 days, and at 1, 2, 4 and 8 weeks after removing the fixator. After the rats were killed, the maximum knee extension angles were measured. Histological sections at the medial mid-condylar region (non-contact, transitional and contact regions of the femur and tibia) were prepared and scored. The cartilage thickness and number of chondrocytes were measured, and CD44 and Col2-3/4c expression levels were assessed immunohistochemically. The histological assessment revealed progressive aggravation of cartilage degeneration in the transitional region, with a decreased number of chondrocytes and CD44-positive chondrocytes as well as poor scoring over time, particularly in the tibia. Cyst formation was confirmed in the transitional region of the tibia at 8 weeks post-remobilization. The cartilage thickness in the transitional region was thicker than that in the contact region, particularly in the tibia. Col2-3/4c expression was observed in the non-contact and transitional regions, and the knee extension angle was recovered. In conclusion, immobilization-induced cartilage degeneration was aggravated by remobilization over time in the transitional region, followed by observations of a decreased number of chondrocytes and morphological disparity between different cartilage regions. PMID- 26989986 TI - The tyrosine kinase inhibitor dasatinib reduces lung inflammation and remodelling in experimental allergic asthma. AB - BACKGROUND AND PURPOSE: Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in understanding of its pathophysiology, asthma remains a major public health problem, and new therapeutic strategies are urgently needed. In this context, we sought to ascertain whether treatment with the TK inhibitor dasatinib might repair inflammatory and remodelling processes, thus improving lung function, in a murine model of asthma. EXPERIMENTAL APPROACH: Animals were sensitized and subsequently challenged, with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, animals were treated with dasatinib, dexamethasone, or saline, every 12 h for 7 consecutive days. Twenty-four hours after the last treatment, the animals were killed, and data were collected. Lung structure and remodelling were evaluated by morphometric analysis, immunohistochemistry, and transmission electron microscopy of lung sections. Inflammation was assessed by cytometric analysis and ELISA, and lung function was evaluated by invasive whole-body plethysmography. KEY RESULTS: In OVA mice, dasatinib, and dexamethasone led to significant reductions in airway hyperresponsiveness. Dasatinib was also able to attenuate alveolar collapse, contraction index, and collagen fibre deposition, as well as increasing elastic fibre content, in OVA mice. Concerning the inflammatory process, dasatinib reduced inflammatory cell influx to the airway and lung-draining mediastinal lymph nodes, without inducing the thymic atrophy promoted by dexamethasone. CONCLUSIONS AND IMPLICATIONS: In this model of allergic asthma, dasatinib effectively blunted the inflammatory and remodelling processes in asthmatic lungs, enhancing airway repair and thus improving lung mechanics. PMID- 26989987 TI - CERK might contribute to inflammatory pain; Comments on Yu WL, Sun. Y (2015). CERK inhibition might be a good potential therapeutic target for diseases. Br J Pharmacol 172: 2165. PMID- 26989988 TI - The change in perceived motor competence and motor task values during elementary school: A longitudinal cohort study. AB - Participation in motor activities is essential for social interaction and life satisfaction in children. Self-perceptions and task values have a central position in why children do or do not participate in (motor) activities. Investigating developmental changes in motor self-perceptions and motor task values in elementary school children would provide vital information about their participation in motor activities. We therefore examined the change in, and associations between, self-perceptions and task values of fine motor competence, ball competence, and athletic competence in 292 children from kindergarten to grade 4. We also investigated differences between boys and girls, and between children with motor problems and typically developing children. Results indicated that self-perceptions and task values are domain specific and differ between boys and girls, but not between children with motor problems and typically developing children. Self-perceptions were not associated with task values. Educators should address specific self-perceptions to enhance participation into the corresponding motor activities in children between kindergarten and grade 4, and differences in self-perceptions and task values between boys and girls should be taken into account. PMID- 26989989 TI - Renewable-Biomolecule-Based Full Lithium-Ion Batteries. AB - A renewable-biomolecule-based full lithium-ion battery is successfully fabricated for the first time. Naturally derivable emodin and humic acid based electrodes are used as cathode and anode, respectively. The as-assembled batteries exhibit superb specific capacity and substantial operating voltage capable of powering a wearable electronic watch, suggesting the great potential for practical applications with the significant merits of sustainability and biocompatibility. PMID- 26989990 TI - Longitudinal effects of prenatal exposure to air pollutants on self-regulatory capacities and social competence. AB - BACKGROUND: We evaluated the influence of prenatal exposure to widespread urban air pollutants on the development of self-regulation and social competence in a longitudinal prospective cohort of children born to nonsmoking minority women in New York City. METHODS: Air pollutant exposure was estimated categorically by level of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in maternal blood collected at delivery, providing a biomarker of maternal exposure to PAH over a 2 to 3-month period. Deficient emotional self-regulation (DESR) was defined as moderate elevations on three specific scales of the child behavior checklist (anxious/depressed, aggressive behavior, and attention problems). We used generalized estimating equations to assess the influence of prenatal exposure to PAH on DESR in children at 3-5, 7, 9, and 11 years of age, adjusted for gender and race/ethnicity. Next, we assessed the association of prenatal exposure to PAH with social competence, as measured by the social responsiveness scale (SRS), the association of impaired self-regulation with social competence, and whether impairment in self-regulation mediated the association of prenatal exposure to PAH with social competence. RESULTS: We detected a significant interaction (at p = .05) of exposure with time, in which the developmental trajectory of self regulatory capacity was delayed in the exposed children. Multiple linear regression revealed a positive association between presence of PAH-DNA adducts and problems with social competence (p < .04), level of dysregulation and problems with social competence (p < .0001), and evidence that self-regulation mediates the association of prenatal exposure to PAH with social competence (p < .0007). CONCLUSIONS: These data suggest that prenatal exposure to PAH produces long-lasting effects on self-regulatory capacities across early and middle childhood, and that these deficits point to emerging social problems with real world consequences for high-risk adolescent behaviors in this minority urban cohort. PMID- 26989991 TI - Using the galactose-alpha-1,3-galactose enzyme-linked immunosorbent assay to predict anaphylaxis in response to cetuximab. AB - BACKGROUND: Cetuximab is a monoclonal antibody against epidermal growth factor receptor with activity against head and neck cancer and colorectal cancer. Anaphylaxis in response to cetuximab is a significant clinical problem in the Southeastern United States with a grade 3/4 infusion reaction rate of 14%. Previous retrospective data have suggested that the presence of preformed immunoglobulin E antibodies against galactose-alpha-1,3-galactose in serum can predict anaphylaxis in response to cetuximab. METHODS: Sixty patients were prospectively screened as part of the entry criteria for a phase 2 study of neoadjuvant carboplatin, nab-paclitaxel, and cetuximab. Patients were recruited at 2 academic medical centers known to have high anaphylaxis rates: the University of North Carolina and Vanderbilt. Only patients with a negative laboratory result were treated on the clinical protocol. RESULTS: No patient experienced anaphylaxis; the negative predictive value was thus 100%. Other than smoking history, the demographics were similar for assay-positive subjects and assay-negative subjects. CONCLUSIONS: Subjects with a negative test result can be safely treated with cetuximab. Further research is required regarding the optimal cutoff for positivity and the positive predictive value. Cancer 2016;122:1697 701. (c) 2016 American Cancer Society. PMID- 26989992 TI - A hot water extract of Aralia cordata activates bone marrow-derived macrophages via a myeloid differentiation protein 88-dependent pathway and protects mice from bacterial infection. AB - In traditional Asian medicine, Aralia cordata (AC) is a known as a pain reliever and anti-inflammatory drug. Although several of its biological activities have been reported, the immunomodulatory effects of a hot water extract of AC (HAC) have not yet been described. The aim of this study was to investigate whether HAC modulates the activation of macrophages, which play important roles in innate immune responses against microbial pathogens, and if so, to determine the molecular mechanisms by which HAC mediates this process. It was found that HAC activates bone marrow-derived macrophages (BMDM) and increases amounts of nitric oxide and proinflammatory cytokines in a dose-dependent manner. In addition, HAC was found to induce phosphorylation of NF-kappaB and mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinases, extracellular signal regulated kinases and p38. Interestingly, these effects were absent in BMDM prepared from myeloid differentiation protein 88-knockout mice. Polysaccharides from HAC exerted stronger immunostimulatory effects than HAC itself. Furthermore, orally administered HAC clearly enhanced clearance of the intracellular pathogen Listeria monocytogenes by boosting innate immune responses. These results demonstrate that HAC exerts immunostimulatory effects through the TLR/MyD88 and NF-kappaB/MAPK signal transduction pathways. PMID- 26989993 TI - Membrane-Filtered Olive Mill Wastewater: Quality Assessment of the Dried Phenolic Rich Fraction. AB - A current trend in olive mill wastewater (OMWW) management is to not only decrease environmental pollution but also to extract and utilize valuable by products. Therefore, the objectives of this study were to explore different techniques for drying a phenolic-rich membrane filtration fraction of OMWW and compare the techniques in terms of the dried product quality and feasibility of the process. The OMWW from 2 (3-phase and 2-phase) California mills was subjected to a 2-step membrane filtration process using a novel vibratory system. The reverse osmosis retentate (RO-R) is a phenolic-rich coproduct stream, and the reverse osmosis permeate is a near-pure water stream that could be recycled into the milling process. Spray-, freeze-, and infrared-drying were applied to obtain solid material from the RO-R. Drying of the RO-R was made possible only with addition of 10% maltodextrin as a carrier. The total soluble phenolics in dried RO-R were in the range 0.15 to 0.58 mg gallic acid equivalents/g of dry weight for 2-phase RO-R, and 1.38 to 2.17 mg gallic acid equivalents/g of dry weight for the 3-phase RO-R. Spray-dried RO-R from 3-phase OMWW showed remarkable antioxidant activity. Protocatechuic acid, tyrosol, vanillic acid, and p-coumaric acid were quantified in all dried RO-R, whereas 3-hydroxytyrosol was found in 3 phase dried RO-R. This combination of separation and drying technologies helps to add value and shelf-stability to an olive oil by-product and increase environmental sustainability of its production. PMID- 26989994 TI - An autoimmune bullous dermatosis with clinical, histopathological and immunological features of bullous pemphigoid and epidermolysis bullosa acquisita in an adult. PMID- 26989995 TI - Predictive factors in non-melanoma skin cancers treated with electrochemotherapy. AB - BACKGROUND: The management of non-melanoma skin cancers may benefit from alternative treatments and in this spectrum electrochemotherapy plays a pivotal role. The aim was to describe the predictive features of patients with cutaneous carcinomas treated with electrochemotherapy, with regard to clinical, pathological and instrumental predictors. METHODS: We analyzed disease free survival (DFS), and overall survival (OS) for each patient. Assuming that the effects of the predictor variables are constant over time, the independent predictive factors were assessed by Cox-proportional hazards regression in both univariate and multivariate analyses. RESULTS: We can assess that in the brief term (DFS), the patients' age, tumor-site, tumor size, photo-type and the dose of the cytotoxic drug showed a statistical significant better behavior. However, in the multivariate, only the variables tumor's site (P=0.01) and tumor appearance (P=0.03) reached the statistical significance. In the long-term, female patients, patients with a median age <=70 years, with III-IV photo types and patients, which received a dosage of bleomycin, <=14 mg/m2 presented a significant better behavior. However in the multivariate analysis a significance was maintained for the variables tumor's appearance (HR: 11.6; 95% CI: 11.56 to 27.5; P=0.01), infiltration (HR:0.11; 95% CI: 0.012 to 0.9; P=0.04), electrode type (HR:0.19; 95% CI:0.04 to 0.8; P=0.03) and photo type (HR:5.7; 95% CI:1.3 to 24.3; P=0.01). CONCLUSIONS: According to our results, in electrochemotherapy different individual variables can have an important influence, which shows how this treatment could improve. The refinement of the technique and the optimization of patients' selection has the aim to improve the therapeutic response. PMID- 26989996 TI - Induced Pectus Carinatum. AB - During the surgical repair of a truncus arteriosus with aortic arch interruption and pulmonary artery origin stenosis, a Contegra conduit was implanted as part of reconstruction of the pulmonary artery in a small infant. There was a mismatch between the conduit size and the patient that resulted in protrusion of the conduit between the sternal edges. To accommodate the conduit inside the thoracic cavity, traction was applied to the sternum that was gradually released over a period of time guided by transesophageal echocardiography-derived cardiac output data, as well as continuous hemodynamic parameters. doi: 10.1111/jocs.12734 (J Card Surg 2016;31:357-360). PMID- 26989997 TI - Machine Learning Based Dimensionality Reduction Facilitates Ligand Diffusion Paths Assessment: A Case of Cytochrome P450cam. AB - In this work we propose an application of a nonlinear dimensionality reduction method to represent the high-dimensional configuration space of the ligand protein dissociation process in a manner facilitating interpretation. Rugged ligand expulsion paths are mapped into 2-dimensional space. The mapping retains the main structural changes occurring during the dissociation. The topological similarity of the reduced paths may be easily studied using the Frechet distances, and we show that this measure facilitates machine learning classification of the diffusion pathways. Further, low-dimensional configuration space allows for identification of residues active in transport during the ligand diffusion from a protein. The utility of this approach is illustrated by examination of the configuration space of cytochrome P450cam involved in expulsing camphor by means of enhanced all-atom molecular dynamics simulations. The expulsion trajectories are sampled and constructed on-the-fly during molecular dynamics simulations using the recently developed memetic algorithms [ Rydzewski, J.; Nowak, W. J. Chem. Phys. 2015 , 143 ( 12 ), 124101 ]. We show that the memetic algorithms are effective for enforcing the ligand diffusion and cavity exploration in the P450cam-camphor complex. Furthermore, we demonstrate that machine learning techniques are helpful in inspecting ligand diffusion landscapes and provide useful tools to examine structural changes accompanying rare events. PMID- 26989999 TI - Stress reactivity speeds basic encoding processes in infants. AB - Acute stress attenuates frontal lobe functioning and increases distractibility while enhancing subcortical processes in both human and nonhuman animals (reviewed by Arnsten [2009] Nature Reviews Neuroscience, 10(6):410-422). To date however these relations have not been examined for their potential effects in developing populations. Here, we examined the relationship between stress reactivity (infants' heart rate response to watching videos of another child crying) and infant performance on measures of looking duration and visual recognition memory. Our findings indicate that infants with increased stress reactivity showed shorter look durations and more novelty preference. Thus, stress appears to lead to a faster, more stimulus-ready attentional profile in infants. Additional work is required to assess potential negative consequences of stimulus-responsivity, such as decreased focus or distractibility. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 546-555, 2016. PMID- 26989998 TI - Successful enrichment and recovery of whole mitochondrial genomes from ancient human dental calculus. AB - OBJECTIVES: Archaeological dental calculus is a rich source of host-associated biomolecules. Importantly, however, dental calculus is more accurately described as a calcified microbial biofilm than a host tissue. As such, concerns regarding destructive analysis of human remains may not apply as strongly to dental calculus, opening the possibility of obtaining human health and ancestry information from dental calculus in cases where destructive analysis of conventional skeletal remains is not permitted. Here we investigate the preservation of human mitochondrial DNA (mtDNA) in archaeological dental calculus and its potential for full mitochondrial genome (mitogenome) reconstruction in maternal lineage ancestry analysis. MATERIALS AND METHODS: Extracted DNA from six individuals at the 700-year-old Norris Farms #36 cemetery in Illinois was enriched for mtDNA using in-solution capture techniques, followed by Illumina high-throughput sequencing. RESULTS: Full mitogenomes (7-34*) were successfully reconstructed from dental calculus for all six individuals, including three individuals who had previously tested negative for DNA preservation in bone using conventional PCR techniques. Mitochondrial haplogroup assignments were consistent with previously published findings, and additional comparative analysis of paired dental calculus and dentine from two individuals yielded equivalent haplotype results. All dental calculus samples exhibited damage patterns consistent with ancient DNA, and mitochondrial sequences were estimated to be 92-100% endogenous. DNA polymerase choice was found to impact error rates in downstream sequence analysis, but these effects can be mitigated by greater sequencing depth. DISCUSSION: Dental calculus is a viable alternative source of human DNA that can be used to reconstruct full mitogenomes from archaeological remains. Am J Phys Anthropol 160:220-228, 2016. (c) 2016 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc. PMID- 26990001 TI - Atrial Fibrillation Predicts Cardiovascular Outcome in Hypertensive Patients With Symptomatic Peripheral Artery Disease and Preserved Ejection Fraction. PMID- 26990000 TI - Conjugation of Uridine with Oleanolic Acid Derivatives as Potential Antitumor Agents. AB - According to fused two bioactive moieties together by bonds covalently and available as a new single hybrid entity known as pharmacophore hybridization, a total of 10 targeted uridine-oleanolic acid hybrids were synthesized. Most of these hybrids showed excellent proliferation inhibition against tested Hep-G2, A549, BGC-823, MCF-7, and PC-3 tumor cell lines (IC50 < 8 MUm), even with some IC50 values under 0.1 MUm. The detection of cytotoxicity selectivity revealed that hybrids 5 and 18 exhibited low cytotoxicity toward normal human liver cell HL-7702. Further studies revealed that selected hybrid 5 could induce apoptosis in Hep-G2 cells through the investigation of acridine orange/ethidium bromide, Hoechst 33258 fluorescence stainings, and annexin V/propidium iodide assay. It was also found that hybrid 5 could induce mitochondrial membrane potential disruption, arrest Hep-G2 cell line at G1 phase, and activate effector caspase 3/9 to trigger cell apoptosis. PMID- 26990002 TI - Vav1 Regulates Mesenchymal Stem Cell Differentiation Decision Between Adipocyte and Chondrocyte via Sirt1. AB - Mesenchymal stem cells (MSCs) are multipotent stromal cells residing in the bone marrow. MSCs have the potential to differentiate to adipocytes, chondrocytes, and other types of cells. In this study, we investigated the molecular mechanism that controls MSC cell fate decisions for differentiation. We found that Vav1, a guanine nucleotide exchange factor for Rho GTPase, was highly expressed in MSCs. Interestingly, loss of Vav1 in MSCs led to spontaneous adipogenic but impaired chondrogenic differentiation, and accordingly Vav1 null mice displayed an increase in fat content and a decrease in cartilage. Conversely, ectopic expression of Vav1 in MSCs reversed this phenotype, and led to enhanced MSC differentiation into chondrocyte but retarded adipogenesis. Mechanistically, loss of Vav1 reduced the level of Sirt1, which was responsible for an increase of acetylated PPARgamma. As acetylation activates PPARgamma, it increased C/EBPalpha expression and promoted adipogenesis. On the other hand, loss of Vav1 resulted in an increase of acetylated Sox9, a target of Sirt1. As acetylation represses Sox9 activity, it led to a dramatic reduction of collagen 2alpha1, a key regulator in chondrocyte differentiation. Finally, we found that Vav1 regulates Sirt1 in MSCs through Creb. Together this study reveals a novel function of Vav1 in regulating MSC cell fate decisions for differentiation through Sirt1. Sirt1 deacetylates PPARgamma and Sox9, two key mediators that control adipocyte and chondrocyte differentiation. The acetylation status of PPARgamma and Sox9 has opposite effects on its activity, thereby controlling cell fate decision. Stem Cells 2016;34:1934-1946. PMID- 26990003 TI - Treatment of Mental or Physical Health Problems in a Combat Zone: Comparisons of Postdeployment Mental Health and Early Separation From Service. AB - The primary aim of this study was to evaluate whether being treated for mental health or nonbattle physical injury during military combat deployment was associated with higher risk for postdeployment mental disorders and poorer career outcomes than seen in the general combat-deployed population. Service members treated in theater for mental health (n = 964) or noncombat injury (n = 853) were compared with randomly sampled personnel (n = 7,220) from the general deployed population on diagnosed mental disorders and early separation from service. Deployment, medical, and career information were obtained from Department of Defense archival databases. Over half of the personnel who received mental health treatment while deployed were diagnosed with 1 or more mental disorders postdeployment and/or were separated from service before completing their full term enlistment. This was significantly higher than expected compared to the general deployed group, adjusting for demographic/military characteristics and mental health history (adjusted odds ratios [ORs] ranging 1.62 to 2.96). Frequencies of problems also were higher in the mental health-treated group than in the group treated for nonbattle physical injuries (significant adjusted ORs ranging 1.65 to 2.58). The documented higher risks for postdeployment adjustment problems suggested that especially those treated in theater by mental health providers might benefit from postdeployment risk-reduction programs. PMID- 26990004 TI - Sex Work Regulation and Sexually Transmitted Infections in Tijuana, Mexico. AB - While reducing the transmission of sexually transmitted infections is a common argument for regulating sex work, relatively little empirical evidence is available regarding the effectiveness of these policies. We investigate the effects of highly publicized sex work regulations introduced in 2005 in Tijuana, Mexico on the incidence of trichomoniasis. State-level, annual data for the 1995 2012 period are employed that include the incidence rates of trichomoniasis by age group and predictor variables. We find that the regulations led to a decrease in the incidence rate of trichomoniasis. Specifically, while our estimates are somewhat noisy, the all-ages incidence rate in the 2005-2012 period is roughly 37% lower than what is predicted by our synthetic control estimates and corresponds to approximately 800 fewer reported cases of trichomoniasis per year. We find that the decreases are especially pronounced for 15-24 and 25-44 age cohorts. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990005 TI - How to manage the logistics of biological therapy. PMID- 26990006 TI - Hardware complications and failure of three-unit zirconia-based and porcelain fused-metal implant-supported fixed dental prostheses: a retrospective cohort study with up to 8 years. AB - OBJECTIVE: The aim of the present study was to assess the hardware complications and survival of three-unit implant-supported zirconia-based fixed dental prostheses (IZ) and implant-supported porcelain-fused-metal fixed dental prostheses (IP). MATERIAL AND METHODS: The study is a retrospective cohort study with up to 8 years (mean 4.8 years) follow-up. Patients with conventional three unit implant-supported fixed dental prostheses (without cantilever) in posterior area were reviewed. Hardware complications and survival rate were evaluated. Chi Square test was used to test the difference between IZ and IP groups. RESULTS: Two hundred and thirty-seven patents (IZ : 112, IP : 125) with 279 three-unit restorations (IZ : 127, IP : 152) participated in the study. The overall survival rate was 95.3% in IZ group and 94.7% in IP group at implant-level and 94.6% in IZ group and 94.4% in IP group at subject-level. Veneer chipping was the most frequently seen complication (20.1%). Significant higher minor veneer chipping rate (Grade 1) was found in IZ group (P = 0.04). No significant difference of veneer chipping rate (Grade 2 and Grade 3) was found between the two groups. The overall hardware complication rates of IZ were significantly higher than IP (33.07% and 18.42%, P = 0.01). CONCLUSION: High survival rate of zirconia-base and Porcelain-fused-to-metal (PFM) restorations can be achieved with up to 8 years follow-up. The zirconia-based restorations need more polishing procedures, maintenance, and professional care than PFM restorations. The number of implants supporting a fixed dental prosthesis did not influence the implant survival and hardware complications. Well-designed studies with high evidence level are still needed to further explore the hardware complications and clinical survival of IZ and IP. PMID- 26990007 TI - Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion. AB - Holder pasteurization (62.5 degrees C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization * Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on beta-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from beta-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with beta-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences. PMID- 26990008 TI - Attentional guidance by relative features: Behavioral and electrophysiological evidence. AB - Our ability to select task-relevant information from cluttered visual environments is widely believed to be due to our ability to tune attention to the particular elementary feature values of a sought-after target (e.g., red, orange, yellow). By contrast, recent findings showed that attention is often tuned to feature relationships, that is, features that the target has relative to irrelevant features in the context (e.g., redder, yellower). However, the evidence for such a relational account is so far exclusively based on behavioral measures that do not allow a safe inference about early perceptual processes. The present study provides a critical test of the relational account, by measuring an electrophysiological marker in the EEG of participants (N2pc) in response to briefly presented distractors (cues) that could either match the physical features of the target or its relative features. In a first experiment, the target color and nontarget color were kept constant across trials. In line with a relational account, we found that only cues with the same relative color as the target were attended, regardless of whether the cues had the same physical color as the target. In a second experiment, we demonstrate that attention is biased to the exact target feature value when the target is embedded in a randomly varying context. Taken together, these results provide the first electrophysiological evidence that attention can modulate early perceptual processes differently; in a context-dependent manner versus a context-independent manner, resulting in marked differences in the range of colors that can attract attention. PMID- 26990009 TI - Identifying Older Adults with Serious Illness: A Critical Step toward Improving the Value of Health Care. AB - OBJECTIVE: To create and test three prospective, increasingly restrictive definitions of serious illness. DATA SOURCES: Health and Retirement Study, 2000 2012. STUDY DESIGN: We evaluated subjects' 1-year outcomes from the interview date when they first met each definition: (A) one or more severe medical conditions (Condition) and/or receiving assistance with activities of daily living (Functional Limitation); (B) Condition and/or Functional Limitation and hospital admission in the last 12 months and/or residing in a nursing home (Utilization); and (C) Condition and Functional Limitation and Utilization. Definitions are increasingly restrictive, but not mutually exclusive. DATA COLLECTION: Of 11,577 eligible subjects, 5,297 met definition A; 3,151 definition B; and 1,447 definition C. PRINCIPAL FINDINGS: One-year outcomes were as follows: hospitalization 33 percent (A), 44 percent (B), 47 percent (C); total average Medicare costs $20,566 (A), $26,349 (B), and $30,828 (C); and mortality 13 percent (A), 19 percent (B), 28 percent (C). In comparison, among those meeting no definition, 12 percent had hospitalizations, total Medicare costs averaged $7,789, and 2 percent died. CONCLUSIONS: Prospective identification of older adults with serious illness is feasible using clinically accessible criteria and may be a critical step toward improving health care value. These definitions may aid clinicians and health systems in targeting patients who could benefit from additional services. PMID- 26990010 TI - Social rank versus affiliation: Which is more closely related to leadership of group movements in Tibetan macaques (Macaca thibetana)? AB - Research on leadership is a critical step for understanding collective decision making. However, only 4 of the 22 extant macaque species have been examined for the impact of social rank and affiliation on the initiation of collective movement. It is far from clear whether such impact exists and, if so, how it works among other macaques. To answer these questions, we investigated free ranging, Tibetan macaques' (Macaca thibetana) group departures from a provisioning area and tested two alternative hypotheses: personal versus distributed leadership. Personal leadership predicts that a single, highest ranking individual initiates the most group movements, whereas distributed leadership predicts that different members lead the group on different occasions and affiliative individuals have more initiations. We recorded how often and how successfully adults initiated group movements from a provisioning area into the forest, and related these variables to the duration of interindividual proximity and grooming time in the forest. All adults initiated group movements, but did so variably. Social rank was related neither to the number of successful initiations nor to the success ratio of initiations. By contrast, eigenvector centrality based on proximity relations was positively correlated with the number and ratio of successful initiations. Moreover, successful initiations were positively correlated with social grooming. Overall, Tibetan macaques showed a pattern of distributed leadership. Our study demonstrated the relationship between social affiliation and individual leadership in a macaque society. Am. J. Primatol. 78:816-824, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990011 TI - Three-dimensional manometry of the upper esophageal sphincter in swallowing and nonswallowing tasks. AB - OBJECTIVES/HYPOTHESIS: High-resolution manometry (HRM) is useful in identifying disordered swallowing patterns and quantifying pharyngeal and upper esophageal sphincter (UES) physiology. HRM is limited by unidirectional sensors and circumferential averaging of pressures, resulting in an imperfect understanding of pressure from asymmetrical pharyngeal anatomy. This study aims to evaluate UES pressures simultaneously from different axial directions. STUDY DESIGN: Case series. METHODS: Three-dimensional HRM was performed on eight healthy subjects to evaluate circumferential UES pressure patterns at rest, during the Valsalva maneuver, and during water swallowing. RESULTS: Multivariate analysis of the variance revealed a significant main effect of circumferential direction on pressure while at rest (P < .001); pressure was greater in the anterior and posterior portions of the UES versus lateral portions. A significant main effect of direction on pressure was not found during the Valsalva maneuver. During swallowing of a 5-mL water bolus, circumferential direction had a significant main effect on pressure immediately before UES pressure dropped (P = .001), while the UES was open (P = .01) and at UES closure (P < .001). There was also a significant main effect of sensor level along the vertical axis on pressure immediately before UES pressure dropped (P = .032) and at UES closure (P < .001). Anterior and posterior pressures were again greater than lateral pressures at all swallowing events. CONCLUSIONS: These results confirm that UES pressures vary significantly based on their circumferential origin, with the majority of the total pressure generated in anterior and posterior regions. Improved understanding of UES pressure in a three-dimensional space can lead to more sophisticated treatments for pharyngeal and UES dysfunction. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2539-2545, 2016. PMID- 26990013 TI - Defined Palladium-Phthalimidato Catalysts for Improved Oxidative Amination. AB - New palladium(II)-phthalimidato complexes have been synthesized, isolated, and structurally characterized. As demonstrated from over 30 examples, they constitute superior catalysts for oxidative amination reactions of alkenes with phthalimide as the nitrogen source. This work streamlines vicinal difunctionalization of alkenes and provides access to significantly improved and experimentally simplified synthetic protocols. PMID- 26990012 TI - IMPACT OF SPECIFIC PHOBIA ON THE RISK OF ONSET OF MENTAL DISORDERS: A 10-YEAR PROSPECTIVE-LONGITUDINAL COMMUNITY STUDY OF ADOLESCENTS AND YOUNG ADULTS. AB - BACKGROUND: The role of specific phobia as a potentially important psychopathological precursor condition to more severe mental disorders is understudied. We examined the prospective-longitudinal association of early childhood/adolescent phobia with subsequent mental disorders and the proportion of outcome disease incidence attributable to specific phobia simultaneously for a broad range of disorders. METHODS: N = 2210 14- to 24-year-old community subjects were followed up for 10 years. DSM-IV-specific phobia as exposure and a broad range of DSM-IV mental disorders as outcomes were assessed with the DSM-IV/M CIDI. Logistic regressions, adjusting for confounders, were used to estimate the associations of specific phobia with the subsequent onset of outcome disorders. RESULTS: Baseline specific phobia predicted the subsequent first onset of anxiety disorders [panic disorder: risk ratio (RR) = 4.38, 95% confidence interval (2.34, 8.21); generalized anxiety disorder: RR = 4.10 (2.19, 7.69); posttraumatic stress disorder: RR = 2.15 (1.13, 4.10); obsessive-compulsive disorder: RR = 3.79 (1.63, 8.82)], affective disorders [major depression: RR = 1.54 (1.16, 2.03); bipolar disorder: RR = 2.20 (1.10, 4.41); dysthymia: RR = 2.75 (1.48, 5.11)], pain disorder: RR = 1.52 (1.14, 2.02), and eating disorders: RR = 2.27 (1.14, 4.51). Population attributable fractions (PAFs; i.e., proportion of outcome disease incidence in the total population attributable to specific phobia) were highest for panic disorder (PAF = 33.93), generalized anxiety disorder (PAF = 32.3), and obsessive-compulsive disorders (PAF = 30.2). CONCLUSION: This study provides strong evidence that specific phobia is an early onset disorder predicting the subsequent onset of a range of disorders. Future studies should examine the underlying mechanisms and the potential of using specific phobia as a target for prevention of subsequent psychopathology. PMID- 26990014 TI - Rhodium(II)-Catalyzed Isomerization of Cyclopropenylmethyl Esters into (Acyloxymethylene)cyclopropanes. AB - In the presence of a rhodium(II) catalyst, 3,3-disubstituted cyclopropenylmethyl esters that possess an electron-rich or neutral aromatic group undergo isomerization into (acyloxymethylene)cyclopropanes. This transformation, which proceeds with inversion of configuration at the stereogenic center, complements the previously disclosed rearrangement reactions of cyclopropenylmethyl esters. The products arising from this new rhodium-catalyzed rearrangement contain an enol ester group that can be subsequently functionalized to access stereodefined arylcyclopropanes. PMID- 26990015 TI - "No One Ever Even Asked Me that Before": Autobiographical Power, Social Defeat, and Recovery among African Americans with Lived Experiences of Psychosis. AB - Our article draws on ethnographic research with African American males diagnosed with a psychotic disorder in a high-poverty urban area of the northeastern United States. Our participants frequently described the ways public mental health services led them to experience a paralyzing erosion of autobiographical power, which we define as the ability to tell one's own story and be the editor of one's own life. We identified three important points when the loss of autobiographical power seemed to perpetuate social defeat or a sense of social powerlessness (Luhrmann 2007) for our participants during their interactions with public mental health care. We invite further inquiry into the loss of autobiographical power in settings of public mental health care, the sense of social defeat it seems to perpetuate, and the impact of these on mental health recovery, especially for people living in contexts of persistent social adversity. PMID- 26990016 TI - Social structure and indirect genetic effects: genetics of social behaviour. AB - The social environment modulates gene expression, physiology, behaviour and patterns of inheritance. For more than 50 years, this concept has been investigated using approaches that include partitioning the social component out of behavioural heritability estimates, studying maternal effects on offspring, and analysing dominance hierarchies. Recent advances have formalized this 'social environment effect' by providing a more nuanced approach to the study of social influences on behaviour while recognizing evolutionary implications. Yet, in most of these formulations, the dynamics of social interactions are not accounted for. Also, the reciprocity between individual behaviour and group-level interactions has been largely ignored. Consistent with evolutionary theory, the principles of social interaction are conserved across a broad range of taxa. While noting parallels in diverse organisms, this review uses Drosophila melanogaster as a case study to revisit what is known about social interaction paradigms. We highlight the benefits of integrating the history and pattern of interactions among individuals for dissecting molecular mechanisms that underlie social modulation of behaviour. PMID- 26990018 TI - Probation Officer Role Emphases and Use of Risk Assessment Information before and after Training. AB - This research examined how probation officers use risk information about offenders, and how its use is affected by what aspects of their role they emphasize. Officers (N = 152) were invited to complete surveys before and after a risk assessment tool training (46.0-65.8% participation rate). Surveys assessed estimates of reoffense and officers' likely supervision approach given a probationer's risk level. Officers tended to overestimate the likelihood of medium- and high-risk offenders to reoffend. As risk level rose, officers tended to increase the number of meetings and referrals. Officers' role emphases were related to how they perceived low-risk offenders' likelihood to reoffend, but not for offenders at other risk levels. There was relative consistency in officers' role emphases, supervision decisions, and responses to violations, so that differences in practice did not appear to be systematic. Most officers' risk perceptions were more realistic after training. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990017 TI - Effectiveness of the STOPP/START (Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria: systematic review and meta-analysis of randomized controlled studies. AB - WHAT IS KNOWN AND OBJECTIVE: STOPP/START are explicit screening tools that identify potentially inappropriate prescribing in older adults. Our objective was to update our 2013 systematic review that showed limited evidence of impact, using new evidence from randomized controlled trials (RCTs) assessing clinical, humanistic and economic outcomes in older adults. METHODS: We performed a search of PubMed, EMBASE, CINAHL, Web of Science and grey literature for RCTs published in English since the previous review through June 2014. The Cochrane Risk of Bias Tool was used. We performed a meta-analysis on the effect of STOPP on potentially inappropriate medication (PIM) rates and a narrative synthesis on other outcomes. RESULTS AND DISCUSSION: Four RCTs (n = 1925 adults) from four countries were included, reporting both acute (n = 2) and long-term care (n = 2) patients. Studies differed in implementation. Two studies were judged to have low risk, and two to have moderate-to-high risk of bias in key domains. Meta-analysis found that the STOPP criteria reduced PIM rates in all four studies, but study heterogeneity (I(2) = 86.7%) prevented the calculation of a meaningful statistical summary. We found evidence that use of the criteria reduces falls, delirium episodes, hospital length-of-stay, care visits (primary and emergency) and medication costs, but no evidence of improvements in quality of life or mortality. WHAT IS NEW AND CONCLUSION: STOPP/START may be effective in improving prescribing quality, clinical, humanistic and economic outcomes. Additional research investigating these tools is needed, especially in frail elderly and community-living patients receiving primary care. PMID- 26990019 TI - MALDI-TOF and nESI Orbitrap MS/MS identify orthogonal parts of the phosphoproteome. AB - Phosphorylation is a reversible posttranslational protein modification which plays a pivotal role in intracellular signaling. Despite extensive efforts, phosphorylation site mapping of proteomes is still incomplete motivating the exploration of alternative methods that complement existing workflows. In this study, we compared tandem mass spectrometry (MS/MS) on matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) and nano-electrospray ionization (nESI) Orbitrap instruments with respect to their ability to identify phosphopeptides from complex proteome digests. Phosphopeptides were enriched from tryptic digests of cell lines using Fe-IMAC column chromatography and subjected to LC-MS/MS analysis. We found that the two analytical workflows exhibited considerable orthogonality. For instance, MALDI-TOF MS/MS favored the identification of phosphopeptides encompassing clear motif signatures for acidic residue directed kinases. The extent of orthogonality of the two LC-MS/MS systems was comparable to that of using alternative proteases such as Asp-N, Arg-C, chymotrypsin, Glu-C and Lys-C on just one LC-MS/MS instrument. Notably, MALDI-TOF MS/MS identified an unexpectedly high number and percentage of phosphotyrosine sites (~20% of all sites), possibly as a direct consequence of more efficient ionization. The data clearly show that LC-MALDI MS/MS can be a useful complement to LC-nESI MS/MS for phosphoproteome mapping and particularly so for acidic and phosphotyrosine containing peptides. PMID- 26990021 TI - Impact of Tetrahydropalmatine on the Pharmacokinetics of Probe Drugs for CYP1A2, 2D6 and 3A Isoenzymes in Beagle Dogs. AB - Tetrahydropalmatine (Tet) exhibit multiple pharmacological activities and is used frequently by clinical practitioners. In this study, we evaluate the in vivo effects of single and repeated oral Tet administrations on CYP1A2, 2D6 and 3A activities in six beagle dogs in a randomized, controlled, open-label, crossover study. A cocktail approach, with dosages of the probe drugs caffeine (3.0 mg/kg), metoprolol (2.33 mg/kg) and midazolam (0.45 mg/kg), was used to measure cytochrome P450 (CYP) metabolic activities. The cocktail was administered orally as a single dose (12 mg/kg) 1 day prior to and 4 days after repeated oral Tet administrations (12 mg/kg three times daily). The probe drugs and their metabolites in plasma were quantified simultaneously by a validated HPLC technique, and non-compartmental parameters were used to evaluate metabolic variables for assessment of CYP inhibition or induction. Tet had no or minor impact on the pharmacokinetics and metabolism of the probe drugs caffeine and metoprolol, CYP1A2 and CYP2D6 substrates, respectively. However, Tet increased AUC0-24 h and decreased AUCratio(0-24 h) (1-hydroxymidazolam/midazolam ratio) for midazolam statistically significant, both in single or multiple dosing of Tet, with up to 39 or 57% increase for AUC0-24 h and 29% or 22 decrease for AUCratio(0 24 h), respectively, in line with previous in vitro findings for its CYP3A4 inhibition. The extensive use of Tet and herbal medicines containing Tet makes Tet a candidate for further evaluation of CYP3A-mediated herb-drug interactions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990020 TI - Growth differentiation factor 15 is a promising diagnostic and prognostic biomarker in colorectal cancer. AB - Although various studies have demonstrated that growth differentiation factor 15 (GDF15) might be a potential diagnostic and prognostic marker in colorectal cancer (CRC) patients, the results are inconsistent and the statistical power of individual studies is also insufficient. An original study was conducted to explore the diagnostic and prognostic value of serum GDF15 in CRC patients. We also conducted a meta-analysis study which aimed to summarize the diagnostic and prognostic performance of serum GDF15 in CRC. We searched PubMed and ISI Web of Knowledge up to 1 November 2014 for eligible studies. In order to explore the diagnostic performance of GDF15, standardized mean difference (SMD) and their 95% confidence intervals (CI) were estimated and receiver-operating characteristic (ROC) curves were constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of serum GDF15 for survival were summarized. A total of eight studies were included in the meta-analyses. Our results revealed that serum GDF15 levels in CRC patients were higher than those in healthy controls (SMD = 1.08, 95% CI: 0.56-1.59, P < 0.001). For discriminating CRC from healthy controls, the AUC of GDF15 was 0.816 (95% CI: 0.792-0.838). The sensitivity and specificity were 58.9% (95% CI: 55.0-62.8) and 92.08% (95% CI: 89.2-94.4), respectively, when a cut-off value of 1099 pg/ml was established. Besides, higher GDF15 expression level was associated with worse overall survival for CRC patients (pooled HR = 2.09, 95% CI: 1.47-2.96). In conclusion, the present meta-analysis suggests that serum GDF15 may be a useful diagnostic and prognostic biomarker for CRC. PMID- 26990022 TI - New insights into the natural history of hepatitis E virus infection through a longitudinal study of multitransfused immunocompetent patients in France. AB - Little is known about the natural history of Hepatitis E virus (HEV) infection in immunocompetent individuals. The prevalence, the course of infection and the occurrence of transmission by transfusion were investigated in multitransfused immunocompetent patients/blood donor pairs included in a longitudinal sample repository collection and followed up between 1988 and 2010. Ninety-eight subjects aged 6-89 years and suffering from acquired haemoglobinopathies were tested for HEV markers (IgM, IgG and RNA) in serial samples collected every 2 or 3 years. Eighteen patients (18.4%) were positive for HEV-IgG at baseline with a prevalence increasing from 12.5% below 26 years to 32% above 56 years. Nine patients remained IgG positive along the study and nine lost their antibodies after a mean follow-up of 7.4 years (1-22 years). One seropositive patient showed an increase of IgG level and RNA-HEV reappearance 1 year after inclusion, suggesting a reinfection and one seroconversion, probably acquired through blood transfusion was observed. This first longitudinal study including immunocompetent individuals confirms that HEV infection is common in Western Europe and that transfusion transmission occurs probably less frequently than expected. In addition, seroreversion and reinfection seem to be common. This suggests that the anti-HEV may not persist overtime naturally. However, repeat exposure to the virus related to the high prevalence of HEV infection may result in a sustainable specific IgG response. PMID- 26990023 TI - Cost-effectiveness of strategy-based approach to treatment of genotype 1 chronic hepatitis C. AB - BACKGROUND AND AIM: The high cost of chronic hepatitis C (HCV) direct-acting antivirals (DAAs) poses significant financial challenges for health payers, especially in Asia. A personalized treatment strategy based on individualized probability of virological response using oral DAAs as second-line therapy would seem practical but has not been studied. METHODS: We performed a Markov model to project health outcomes and costs for patients with genotype 1 HCV through 10 treatment strategies over a lifetime period. The implication of retreatment was also incorporated to reflect real-life situation. RESULTS: Using boceprevir and peginterferon/ribavirin (BOC/PR, the least costly treatment) as a base case, the all-oral therapies such as ombitasvir/paritaprevir/ritonavir-dasabuvir are cost effective with an incremental cost-effective ratio of $US50 828. However, the all oral DAAs would no longer be cost-effective compared with conventional therapies if retreatment were taken into account. A road map strategy using rapid virological response to guide use of BOC/PR and sofosbuvir/PR had the most favorable incremental cost-effective ratio ($US27 782) relative to BOC/PR. Nevertheless, the trade-off with the cost-effectiveness of the road map strategy is an increased number of liver-related deaths compared with all-oral DAAs (52 vs 10-20 per 10 000 patients) by incorporating retreatment. CONCLUSIONS: The 12-week all-oral DAAs were cost-effective options using conventional drug-to-drug comparison. However, they cease to be cost-effective when treatment strategies incorporating DAA retreatment for interferon failures are incorporated. HCV management can be optimized by adopting individualized treatment algorithm providing a practical solution to health payers to make oral DAAs accessible to those who need them most. PMID- 26990024 TI - Recent advances in robot-assisted head and neck surgery. AB - OBJECTIVE: This article reviews current clinical applications and experimental developments for robotic surgery in the head and neck with special focus on financial challenges, current clinical trials, and the controversial aspect of haptic and tactile feedback. DATA SOURCES: Literature was screened using the pubmed library. Information on clinical trials was excerpted from the National Institute of Health database. Additional data on experimental developments were gathered by personal communication. RESULTS: A steep increase in clinical applications for robotic surgery in the head and neck is determined as possible indications extend. Clinical trials are mostly non-randomized. A wide range of new robotic systems are expected to come into clinical use in the near future. CONCLUSION: As head and neck surgeons become more familiar with robotic surgery some patients evidently benefit from new technologies. Increased competition between the systems will certainly drive technological improvement and decrease the financial burden. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990025 TI - The application of next-generation sequencing-based molecular diagnostics in endometrial stromal sarcoma. AB - AIMS: Endometrial stromal sarcomas (ESSs) are divided into low-grade and high grade subtypes, with the latter showing more aggressive clinical behaviour. Although histology and immunophenotype can aid in the diagnosis of these tumours, genetic studies can provide additional diagnostic insights, as low-grade ESSs frequently harbour fusions involving JAZF1/SUZ12 and/or JAZF1/PHF1, whereas high grade ESSs are defined by YWHAE-NUTM2A/B fusions. The aim of this study was to evaluate the utility of a next-generation sequencing (NGS)-based assay in identifying ESS fusions in archival formalin-fixed paraffin-embedded tumour samples. METHODS AND RESULTS: We applied an NGS-based fusion transcript detection assay (Archer FusionPlex Sarcoma Panel) that targets YWHAE and JAZF1 fusions in a series of low-grade ESSs (n = 11) and high-grade ESSs (n = 5) that were previously confirmed to harbour genetic rearrangements by fluorescence in-situ hybridization (FISH) and/or reverse transcription polymerase chain reaction (RT PCR) analyses. The fusion assay identified junctional fusion transcript sequences that corresponded to the known FISH/RT-PCR results in all cases. Four low-grade ESSs harboured JAZF1-PHF1 fusions with different junctional sequences, and all were correctly identified because of the open-ended nature of the assay design, using anchored multiplex polymerase chain reaction. Seven non-ESS sarcomas were also included as negative controls, and no strong ESS fusion candidates were identified in these cases. CONCLUSIONS: Our findings demonstrate good sensitivity and specificity of an NGS-based gene fusion assay in the detection of ESS fusion transcripts. PMID- 26990026 TI - Differential responses of tetrasporophytes and gametophytes of Mazzaella laminarioides (Gigartinales, Rhodophyta) under solar UV radiation. AB - The effects of solar UV radiation on mycosporine-like amino acids (MAAs), growth, photosynthetic pigments (Chl a, phycobiliproteins), soluble proteins (SP), and C and N content of Mazzaella laminarioides tetrasporophytes and gametophytes were investigated. Apical segments of tetrasporophytes and gametophytes were exposed to solar radiation under three treatments (PAR [P], PAR+UVA [PA], and PAR+UVA+UVB [PAB]) during 18 d in spring 2009, Punta Arenas, Chile. Samples were taken after 2, 6, 12, and 18 d of solar radiation exposure. Most of the parameters assessed on M. laminarioides were significantly influenced by the radiation treatment, and both gametophytes and tetrasporophytes seemed to respond differently when exposed to high UV radiation. The two main effects promoted by UV radiation were: (i) higher synthesis of MAAs in gametophytes than tetrasporophytes at 2 d, and (ii) a decrease in phycoerythrin, phycocyanin, and SPs, but an increase in MAA content in tetrasporophytes at 6 and 12 d of culture. Despite some changes that were observed in biochemical parameters in both tetrasporophytes and gametophytes of M. laminarioides when exposed to UVB radiation, these changes did not promote deleterious effects that might interfere with the growth in the long term (18 d). The tolerance and resistance of M. laminarioides to higher UV irradiance were expected, as this intertidal species is exposed to variation in solar radiation, especially during low tide. PMID- 26990028 TI - Transthoracic needle aspiration biopsy for the cytologic diagnosis of subsolid lung nodules. PMID- 26990027 TI - Structure-Based Virtual Screening for Dopamine D2 Receptor Ligands as Potential Antipsychotics. AB - Structure-based virtual screening using a D2 receptor homology model was performed to identify dopamine D2 receptor ligands as potential antipsychotics. From screening a library of 6.5 million compounds, 21 were selected and were subjected to experimental validation. From these 21 compounds tested, ten D2 ligands were identified (47.6% success rate, among them D2 receptor antagonists, as expected) that have additional affinity for other receptors tested, in particular 5-HT2A receptors. The affinity (Ki values) of the compounds ranged from 58 nm to about 24 MUM. Similarity and fragment analysis indicated a significant degree of structural novelty among the identified compounds. We found one D2 receptor antagonist that did not have a protonatable nitrogen atom, which is a key structural element of the classical D2 pharmacophore model necessary for interaction with the conserved Asp(3.32) residue. This compound exhibited greater than 20-fold binding selectivity for the D2 receptor over the D3 receptor. We provide additional evidence that the amide hydrogen atom of this compound forms a hydrogen bond with Asp(3.32), as determined by tests of its derivatives that cannot maintain this interaction. PMID- 26990029 TI - Total uterine artery blood volume flow rate in nulliparous women is associated with birth weight and gestational age at delivery. AB - OBJECTIVES: To investigate the relationship between total uterine artery blood volume flow rate (TVFR) and birth weight and gestational age at delivery, and to establish normal ranges of TVFR throughout pregnancy. METHODS: This was a prospective cohort study of 334 nulliparous women booking antenatal care at University College London Hospital between August 2008 and September 2009. Women underwent a transabdominal ultrasound examination of uterine arteries for measurement of TVFR at 12, 20 and 24 weeks' gestation. Pregnancy outcomes were recorded and linear regression was used to study the relationship between TVFR and gestational age at delivery and birth weight. RESULTS: A total of 551 ultrasound scans were performed. There was a significant, positive correlation between TVFR at 11-13 weeks (TVFR1) and at 22-26 weeks (TVFR3) and birth weight. For every 100-mL/min increase in TVFR1 and TVFR3, there was an increase in birth weight of 45 g and 27 g, respectively. There was also a positive association between TVFR1 and gestational age at delivery, with a 1.4-day increase in gestational age for every 100-mL/min increase of TVFR1. CONCLUSION: Ultrasound measurement of TVFR in the first trimester is significantly associated with both birth weight and gestational age at delivery. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26990030 TI - Sputum interleukin-13 as a biomarker for the evaluation of asthma control. AB - BACKGROUND: Asthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin-13 (IL-13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control. OBJECTIVE: To assess the diagnostic performance of sputum IL-13 for the evaluation of asthma control and furthermore to investigate the performance of sputum eosinophils and FeNO. METHODS: One hundred and seventy patients with asthma were studied. All subjects underwent assessment of asthma control by asthma control test (ACT), lung function tests, FeNO measurement and sputum induction for cell count identification and IL-13 measurement in supernatants. RESULTS: IL-13 (pg/mL) levels in sputum supernatant differed significantly among patients with well-controlled asthma and those with not well-controlled asthma [median IQR 78 (66-102) vs. 213 (180-265), P < 0.001]. Receiver operating characteristic (ROC) analysis showed that, for the whole study population, the diagnostic performance of IL-13 was superior to both sputum eosinophils and FeNO levels [area under the curve (AUC) 0.92, 95% CI 0.87 to 0.95 vs. AUC 0.65, 95% CI 0.58 to 0.72 vs. AUC 0.65, 95% CI 0.55 to 0.72, respectively]. CONCLUSION: The diagnostic performance of sputum IL-13 was superior to both sputum eosinophils and FeNO levels for the identification of well-controlled asthma. Sputum IL-13 levels could serve as a useful biomarker for asthma control assessment. PMID- 26990032 TI - Correlative NAD(P)H-FLIM and oxygen sensing-PLIM for metabolic mapping. AB - Cellular responses to oxygen tension have been studied extensively. Oxygen tension can be determined by considering the phosphorescence lifetime of a phosphorescence sensor. The simultaneous usage of FLIM of coenzymes as NAD(P)H and FAD(+) and PLIM of oxygen sensors could provide information about correlation of metabolic pathways and oxygen tension. We investigated correlative NAD(P)H FLIM and oxygen sensing-PLIM for simultaneously analyzing cell metabolism and oxygen tension. Cell metabolism and pO2 were observed under different hypoxic conditions in squamous carcinoma cell cultures and in complex ex vivo systems. Increased hypoxia induced an increase of the phosphorescence lifetime of Ru(BPY)3 and in most cases a decrease in the lifetime of NAD(P)H which is in agreement to the expected decrease of the protein-bound NAD(P)H during hypoxia. Oxygen was modulated directly in the mitochondrial membrane. Blocking of complex III and accumulation of oxygen could be observed by both the decrease of the phosphorescence lifetime of Ru(BPY)3 and a reduction of the lifetime of NAD(P)H which was a clear indication of acute changes in the redox state of the cells. For the first time simultaneous FLIM/PLIM has been shown to be able to visualize intracellular oxygen tension together with a change from oxidative to glycolytic phenotype. PMID- 26990031 TI - Fibrolamellar Hepatocellular Carcinoma: Mechanistic Distinction From Adult Hepatocellular Carcinoma. AB - Fibrolamellar hepatocellular carcinoma (FL-HCC) has historically been classified as a rare subtype of HCC. However, unlike "classic" HCC, it occurs in children and young adults without underlying liver disease. The recent discovery of a deletion mutation in all FL-HCCs represented a major advancement in understanding the pathogenesis of this disease. This deletion results in the fusion of the genes encoding a heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PKA, PRKACA), and overexpression of PRKACA and enhanced cAMP-dependent PKA activity. This review summarizes recent advancements in FL-HCC pathogenesis and characteristics of the HSP40-PKA C protein. PMID- 26990033 TI - Tirapazamine has no Effect on Hepatotoxicity of Cisplatin and 5-fluorouracil but Interacts with Doxorubicin Leading to Side Changes in Redox Equilibrium. AB - Tirapazamine is a hypoxia-activated prodrug which was shown to exhibit up to 300 times greater cytotoxicity under anoxic in comparison with aerobic conditions. Thus, the combined anticancer therapy of tirapazamine with a routinely used anticancer drug seems to be a promising solution. Because tirapazamine undergoes redox cycle transformation in this study, the effect of tirapazamine on redox hepatic equilibrium, lipid status and liver morphology was evaluated in rats exposed to cisplatin, doxorubicin and 5-fluorouracil. Rats were intraperitoneally injected with tirapazamine and a particular cytostatic. The animals were killed, and blood and liver were collected. Hepatic glucose, total cholesterol, triglycerides, NADH, NADPH glutathione and the activity of glucose-6-phosphate dehydrogenase were determined. Liver morphology and the immune expression of HMG CoA-reductase were also assessed. Glucose, total cholesterol, triglycerides, bilirubin concentrations and the activity of aspartate and alanine aminotransferases were determined in the plasma. Tirapazamine displayed insignificant interactions with cisplatin and 5-fluorouracil referring to hepatic morphology and biochemical parameters. However, tirapazamine interacts with doxorubicin, thus leading to side changes in redox equilibrium and lipid peroxidation, but those effects are not severe enough to exclude that drug combination from further studies. Thus, tirapazamine seems to be a promising agent in successive studies on anticancer activity in similar schedules. PMID- 26990034 TI - Inequality and childhood overweight and obesity: a commentary. AB - Statements on childhood overweight and obesity (COO) have focused on different avenues for prevention and treatment, critical stages of the life cycle, including pregnancy and lactation, individual, family, school and community-based interventions, multidisciplinary family programmes and multicomponent interventions. This commentary is concerned with the less-addressed relationship between COO and inequality. It describes current global patterns of inequality and COO and the ways in which those inequalities are linked to COO at micro level, meso-level and macro-level. It then describes current programmatic approaches for COO inequality, preventive and medical, and considers important pitfalls in the framing of the problem of COO and inequality. It ends with describing how childhood and adolescent overweight and obesity prevention and treatment programmes might be formulated within broader socio-political frameworks to influence outcomes. PMID- 26990036 TI - Mutuality in health care: review, concept analysis and ways forward. AB - AIMS AND OBJECTIVES: This paper aims to critically investigate the notion of mutuality in nursing, and explore how to resolve the tension between individualised accounts of mutuality and institutional and political factors. BACKGROUND: The concept of mutuality underlies many theories and models of nursing yet this does not capture the power relations in health care or institutional constraints on mutuality. DESIGN: This is a position paper informed by a narrative literature review. METHODS: A search of the Scopus, PubMed, Web of Knowledge and CINAHL databases for the terms mutual, mutuality and nursing was conducted, to capture English language literature published from 1990 to mid 2015. RESULTS: There is a large literature discussing the nature and value of mutual exchange and mutuality. There is acknowledgement of institutional and professional constraints which limit the potential of mutuality. Yet there is often a reluctance to engage with critical thinking which emphasises the inequalities of power in health care situations. Accordingly, the notion of social capital is introduced, which emphasises the role of social relationships which individuals and groups can deploy to their advantage. Finally the paper explores how new thinking about mutuality and social capital can make health care more effective. CONCLUSIONS: Mutuality and social capital can be enhanced in a variety of ways and may improve client and practitioner outcomes via training, educational and organisational design, and initiatives involving patients and service users, as well as practitioners and service leaders. RELEVANCE TO CLINICAL PRACTICE: The sociologically nuanced account of mutuality advanced here sensitises us to questions of power and domination, as well as enabling us to see mutuality in terms of networks of relationships instead of merely an interpersonal phenomenon. This enables practitioners to enhance clients' and their own capacity for mutuality and develop effective resources to increase resilience and recovery. PMID- 26990035 TI - Pharmacokinetics and pharmacodynamics of propofol and fentanyl in patients undergoing abdominal aortic surgery - a study of pharmacodynamic drug-drug interactions. AB - Propofol is routinely combined with opioid analgesics to ensure adequate anesthesia during surgery. The aim of the study was to assess the effect of fentanyl on the hypnotic effect of propofol and the possible clinical implications of this interaction. The pharmacokinetic/pharmacodynamic (PK/PD) data were obtained from 11 patients undergoing abdominal aortic surgery, classified as ASA III. Propofol was administered by a target-controlled infusion system. Fentanyl 2-3 ug/kg was given whenever insufficient analgesia occurred. The bispectral index (BIS) was used to monitor the depth of anesthesia. A population PK/PD analysis with a non-linear mixed-effect model (NONMEM 7.2 software) was conducted. Two-compartment models satisfactorily described the PK of propofol and fentanyl. The delay of the anesthetic effect in relation to PK was described by the effect compartment. The BIS was linked to propofol and fentanyl effect-site concentrations through an additive Emax model. Context sensitive decrement times (CSDT) determined from the final model were used to assess the influence of fentanyl on the recovery after anesthesia. The population PK/PD model was successfully developed to describe simultaneously the time course and variability of propofol and fentanyl concentrations and BIS. Additive propofol-fentanyl interactions were observed and quantitated. The duration of the fentanyl infusion had minimal effect on CSDT when it was shorter than the duration of the propofol infusion. If the fentanyl infusion was longer than the propofol infusion, an almost two-fold increase in CSDT occurred. Additional doses of fentanyl administered after the cessation of the propofol infusion result in lower BIS values, and can prolong the time of recovery from anesthesia. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990037 TI - Diagnostic accuracy of repetition tasks for the identification of specific language impairment (SLI) in bilingual children: evidence from Russian and Hebrew. AB - BACKGROUND: Previous research demonstrates that repetition tasks are valuable tools for diagnosing specific language impairment (SLI) in monolingual children in English and a variety of other languages, with non-word repetition (NWR) and sentence repetition (SRep) yielding high levels of sensitivity and specificity. Yet, only a few studies have addressed the diagnostic accuracy of repetition tasks in bilingual children, and most available research focuses on English Spanish sequential bilinguals. AIMS: To evaluate the efficacy of three repetition tasks (forward digit span (FWD), NWR and SRep) in order to distinguish mono- and bilingual children with and without SLI in Russian and Hebrew. METHODS & PROCEDURES: A total of 230 mono- and bilingual children aged 5;5-6;8 participated in the study: 144 bilingual Russian-Hebrew-speaking children (27 with SLI); and 52 monolingual Hebrew-speaking children (14 with SLI) and 34 monolingual Russian speaking children (14 with SLI). Parallel repetition tasks were designed in both Russian and Hebrew. Bilingual children were tested in both languages. OUTCOMES & RESULTS: The findings confirmed that NWR and SRep are valuable tools in distinguishing monolingual children with and without SLI in Russian and Hebrew, while the results for FWD were mixed. Yet, testing of bilingual children with the same tools using monolingual cut-off points resulted in inadequate diagnostic accuracy. We demonstrate, however, that the use of bilingual cut-off points yielded acceptable levels of diagnostic accuracy. The combination of SRep tasks in L1/Russian and L2/Hebrew yielded the highest overall accuracy (i.e., 94%), but even SRep alone in L2/Hebrew showed excellent levels of sensitivity (i.e., 100%) and specificity (i.e., 89%), reaching 91% of total diagnostic accuracy. CONCLUSIONS & IMPLICATIONS: The results are very promising for identifying SLI in bilingual children and for showing that testing in the majority language with bilingual cut-off points can provide an accurate classification. PMID- 26990038 TI - Improved Efficiency of Molecular-Gel Formation by Adjusting Preorganization of Amino-Acid-Derived Flexible Molecules: A NMR and Thermodynamic study. AB - The efficiency of the formation of molecular gels of simple derivatives of l valine and l-isoleucine is greatly improved in different organic solvents when a hexyl fragment is replaced by a bulkier cyclohexyl one. A study using NMR and IR spectroscopy provides information on the preferred conformations of the molecules, indicating that the cyclohexyl moiety precludes intramolecular H bonding and preorganises the system for intermolecular interactions, which are responsible for fiber formation. NMR data of the gels provides thermodynamic data on fibrillization, revealing that the origin of this effect is mainly entropic. Electron microscopy (SEM and TEM) images show fibrillar and tape-like objects, which are observed commonly in molecular gels. Rheological measurements reveal significant differences between cyclohexyl and hexyl appended gelators. These findings could contribute to the rational design of small, flexible, building blocks for self-assembly. PMID- 26990039 TI - Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota. AB - SCOPE: Binge consumption of alcohol is an alarming global health problem. Acute ethanol intoxication is characterized by hepatic inflammation and oxidative stress, which could be promoted by gut barrier function alterations. In this study, we have tested the hypothesis of the hepatoprotective effect of rhubarb extract in a mouse model of binge drinking and we explored the contribution of the gut microbiota in the related metabolic effects. METHODS AND RESULTS: Mice were fed a control diet supplemented with or without 0.3% rhubarb extract for 17 days and were necropsied 6 h after an alcohol challenge. Supplementation with rhubarb extract changed the microbial ecosystem (assessed by 16S rDNA pyrosequencing) in favor of Akkermansia muciniphila and Parabacteroides goldsteinii. Furthermore, it improved alcohol-induced hepatic injury, downregulated key markers of both inflammatory and oxidative stresses in the liver tissue, without affecting significantly steatosis. In the gut, rhubarb supplementation increased crypt depth, tissue weight, and the expression of antimicrobial peptides. CONCLUSIONS: These findings suggest that some bacterial genders involved in gut barrier function, are promoted by phytochemicals present in rhubarb extract, and could therefore be involved in the modulation of the susceptibility to hepatic diseases linked to acute alcohol consumption. PMID- 26990040 TI - Placebo-controlled assessment of somnolence effect of cetirizine: a meta analysis. AB - BACKGROUND: It has been found that the most common adverse reaction which occurs more frequently on cetirizine than on placebo is somnolence. However, the somnolence rate varied widely among different studies. The objective of this study was to assess the somnolence effect of cetirizine 10 mg daily compared to placebo in patients aged 6 years and older using meta-analysis and explore the sources of heterogeneity among different studies. METHODS: Databases were searched for randomized controlled trials (RCTs) of cetirizine published before 2015. Overall risk differences (RDs) were determined by meta-analyses of 13 trials using the DerSimonian and Laird (D&L) method based on fixed-effects and random-effect models, respectively. The Q statistic, H statistic, and I(2) were calculated for heterogeneity analysis. Subgroup analysis, Galbraith plot, sensitivity analysis, and meta-regression were also performed to explore the sources of heterogeneity. RESULTS: Various analyses showed that heterogeneity existed among the 13 trials and the placebo run-in period was the cause of heterogeneity. For RCTs without and with placebo run-in period, the overall RDs were 6.51% (95% CI, 4.47% to 8.56%) and 1.03% (95% CI, -0.13% to 2.19%), respectively, which indicated that the difference in somnolence rate between cetirizine 10 mg daily and placebo was not statistically significant for the subgroup with placebo run-in. CONCLUSION: The meta-analysis showed that the RDs between cetirizine 10 mg daily and placebo on somnolence rate were different for studies with and without a placebo run-in period. The results for studies with a placebo run-in period suggested that cetirizine 10 mg daily has no somnolence effect compared to placebo. PMID- 26990041 TI - Soft tissue volume alterations after connective tissue grafting at teeth: the subepithelial autologous connective tissue graft versus a porcine collagen matrix - a pre-clinical volumetric analysis. AB - AIM: This study evaluates a porcine collagen matrix (CM) for soft tissue thickening in comparison to the subepithelial connective tissue graft (SCTG). MATERIAL AND METHODS: In eight beagle dogs, soft tissue thickening was performed at the buccal aspects of the upper canines (SCTG and CM). Impressions were taken before augmentation (i1), after surgery (i2), after one (i3), three (i4) and ten month (i5). Casts were optically scanned with a 3D scanner and each augmented region (unit of analysis) evaluated (primary outcome variable: volume increase in mm(3) ; secondary outcome variables: volume increase in percent, mean and maximum thickness increases in mm). RESULTS: 3D tissue measurements after surgery revealed a significant higher volume increase in the CM (86.37 mm(3) +/- 35.16 mm(3) ) than in the SCTG group (47.65 mm(3) +/- 17.90 mm(3) ). After 10 months, volume increase was non-significant between groups (SCTG:11.36 mm(3) +/- 9.26 mm(3) ; CM: 8.67 mm(3) +/- 13.67 mm(3) ). Maximum soft tissue thickness increase (i1-i5) was 0.66 mm +/- 0.29 mm (SCTG) and 0.79 mm +/- 0.37 mm (CM) with no significant difference. CONCLUSIONS: Ten months after soft tissue thickening, the CM is statistically non-inferior to the SCTG in terms of soft tissue volume and thickness increase. Further 3D studies are needed to confirm the data. PMID- 26990042 TI - Glass Formation of a Coordination Polymer Crystal for Enhanced Proton Conductivity and Material Flexibility. AB - The glassy state of a two-dimensional (2D) Cd(2+) coordination polymer crystal was prepared by a solvent-free mechanical milling process. The glassy state retains the 2D structure of the crystalline material, albeit with significant distortion, as characterized by synchrotron X-ray analyses and solid-state multinuclear NMR spectroscopy. It transforms to its original crystal structure upon heating. Thus, reversible crystal-to-glass transformation is possible using our new processes. The glass state displays superior properties compared to the crystalline state; specifically, it shows anhydrous proton conductivity and a dielectric constant two orders of magnitude greater than the crystalline material. It also shows material flexibility and transparency. PMID- 26990043 TI - Glycemic control and the heart: it matters how you get there. PMID- 26990044 TI - DNA Sequential Logic Gate Using Two-Ring DNA. AB - Sequential DNA detection is a fundamental issue for elucidating the interactive relationships among complex gene systems. Here, a sequential logic DNA gate was achieved by utilizing the two-ring DNA structure, with the ability to recognize "before" and "after" triggering sequences of DNA signals. By taking advantage of a "loop-open" mechanism, separations of two-ring DNAs were controlled. Three triggering pathways with different sequential DNA treatments were distinguished by comparing fluorescent outputs. Programmed nanoparticle arrangement guided by "interlocked" two-ring DNA was also constructed to demonstrate the achievement of designed nanostrucutres. Such sequential logic DNA operation may guide future molecular sensors to monitor more complex gene network in biological systems. PMID- 26990045 TI - Gender differences in patients with obesity hypoventilation syndrome. AB - The role of gender and menopause in obstructive sleep apnoea is well known; however, no study has reported the impact of gender on the clinical presentation and the nocturnal respiratory events in patients with obesity hypoventilation syndrome. Therefore, this study prospectively evaluated differences in the clinical characteristics of women and men with obesity hypoventilation syndrome in a large cohort of patients with obstructive sleep apnoea. During the study period, a total of 1973 patients were referred to the sleep clinic with clinical suspicion of obstructive sleep apnoea. All patients underwent overnight polysomnography, during which time spirometry, arterial blood samples and thyroid tests were routinely obtained. Among 1973 consecutive patients, 1693 (617 women) were diagnosed with obstructive sleep apnoea, among whom 144 suffered from obesity hypoventilation syndrome (96 women). The prevalence of obesity hypoventilation syndrome among women and men was 15.6% and 4.5%, respectively (P < 0.001). Women with obesity hypoventilation syndrome were significantly older than men with obesity hypoventilation syndrome (61.5 +/- 11.9 years versus 49.1 +/- 12.5 years, P < 0.001). Although there were no significant differences between genders regarding symptoms, body mass index, spirometric data or daytime PaCO2 , women with obesity hypoventilation syndrome suffered significantly more from hypertension, diabetes and hypothyroidism. The prevalence of obesity hypoventilation syndrome was higher in post-menopausal (21%) compared with pre menopausal (5.3%) women (P < 0001). HCO3 and duration of SpO2 <90% were the only independent predictors of obesity hypoventilation syndrome. In conclusion, this study reported that among subjects referred to the sleep disorders clinic for evaluation of obstructive sleep apnoea, obesity hypoventilation syndrome is more prevalent in women than men, and that women with obesity hypoventilation syndrome suffer from significantly more co-morbidities. Post-menopausal women with obstructive sleep apnoea have the highest prevalence of obesity hypoventilation syndrome. PMID- 26990046 TI - Iodine-125 seeds to guide removal of impalpable breast lesions: radio-guided occult lesion localization - a pilot study. AB - BACKGROUND: The aim of this study was to confirm that radio-guided occult lesion localization using low activity iodine 125 (I-125) seeds (ROLLIS) could be safely and accurately used for localization and guided excision of impalpable breast lesions in different multidisciplinary settings and to prepare staff for a randomized controlled trial. METHOD: Preoperative image-guided localization of 102 lesions using one or two I-125 seeds with hook-wire back-up was performed in 99 participants at two tertiary hospitals. Preoperative core biopsy in 24 lesions was benign or indeterminate (Group A) and malignant in 78 lesions (Group B). Imaging and histopathology findings and re-excision rates were recorded. Training requirements for new staff and seed handling protocols were refined. RESULTS: All seeds and lesions were successfully removed. In five of 23 Group A participants, malignancy on final pathology required definitive surgery for positive margins. The re-excision rate in Group B was 17%. Overall re-excision rate was 18%. Thirty seven clinical staff members were trained. Sentinel node localization was successful in all 76 cases. Seeds of low activity were successfully used. CONCLUSION: The ROLLIS technique using a lower dose (~2 MBq) seed is safe, effective and can easily be adopted in a large multi-disciplinary setting. PMID- 26990047 TI - LINE1 insertions as a genomic risk factor for schizophrenia: Preliminary evidence from an affected family. AB - Recent studies show that human-specific LINE1s (L1HS) play a key role in the development of the central nervous system (CNS) and its disorders, and that their transpositions within the human genome are more common than previously thought. Many polymorphic L1HS, that is, present or absent across individuals, are not annotated in the current release of the genome and are customarily termed "non reference L1s." We developed an analytical workflow to identify L1 polymorphic insertions with next-generation sequencing (NGS) using data from a family in which SZ segregates. Our workflow exploits two independent algorithms to detect non-reference L1 insertions, performs local de novo alignment of the regions harboring predicted L1 insertions and resolves the L1 subfamily designation from the de novo assembled sequence. We found 110 non-reference L1 polymorphic loci exhibiting Mendelian inheritance, the vast majority of which are already reported in dbRIP and/or euL1db, thus, confirming their status as non-reference L1 polymorphic insertions. Four previously undetected L1 polymorphic loci were confirmed by PCR amplification and direct sequencing of the insert. A large fraction of our non-reference L1s is located within the open reading frame of protein-coding genes that belong to pathways already implicated in the pathogenesis of schizophrenia. The finding of these polymorphic variants among SZ offsprings is intriguing and suggestive of putative pathogenic role. Our data show the utility of NGS to uncover L1 polymorphic insertions, a neglected type of genetic variants with the potential to influence the risk to develop schizophrenia like SNVs and CNVs. (c) 2016 Wiley Periodicals, Inc. PMID- 26990048 TI - The Impact of Interlayer Electronic Coupling on Charge Transport in Organic Semiconductors: A Case Study on Titanylphthalocyanine Single Crystals. AB - Traditionally, it is believed that three-dimensional transport networks are preferable to those of lower dimensions. We demonstrate that inter-layer electronic couplings may result in a drastic decrease of charge mobilities by utilizing field-effect transistors (FET) based on two phases of titanyl phthalocyanine (TiOPc) crystals. The alpha-phase crystals with electronic couplings along two dimensions show a maximum mobility up to 26.8 cm(2) V(-1) s(-1) . In sharp contrast, the beta-phase crystals with extra significant inter layer electronic couplings show a maximum mobility of only 0.1 cm(2) V(-1) s( 1) . Theoretical calculations on the bulk crystals and model slabs reveal that the inter-layer electronic couplings for the beta-phase devices will diminish remarkably the device charge transport abilities owing to the coupling direction perpendicular to the current direction. This work provides new insights into the impact of the dimensionality and directionality of the packing arrangements on charge transport in organic semiconductors. PMID- 26990049 TI - Pulmonary thromboembolism as a result of ovarian vein thrombosis after laparoscopic-assisted vaginal hysterectomy for uterine myoma. AB - Pulmonary thromboembolism is a potentially life-threatening disorder, which can occur secondary to deep vein thrombosis. Ovarian vein thrombosis has classically been considered to be a postpartum complication and is less frequently associated with other disease processes, such as recent pelvic surgery. Herein, we report a case of pulmonary thromboembolism as a result of ovarian vein thrombosis in a 39 year-old woman after an uneventful laparoscopic-assisted vaginal hysterectomy for uterine myoma. On postoperative day 3, the patient experienced fever of unknown origin, followed by lower abdominal pain, chest discomfort and shortness of breath. A hematological examination revealed an elevated D-dimer level. Computerized tomography revealed pulmonary thromboembolism caused by left ovarian vein thrombosis. The administration of anticoagulants resolved the symptoms. In order to avoid significant morbidities and potential mortality, attention should be paid to the possibility of pulmonary thromboembolism resulting from ovarian vein thrombosis, even after minimally invasive gynecologic surgery for benign conditions. PMID- 26990050 TI - Cryptococcal therapies and drug targets: the old, the new and the promising. AB - Half a century after the introduction of Amphotericin B the management of cryptococcosis remains unsatisfactory. The disease, caused primarily by the two fungal species Cryptococcus neoformans and Cryptococcus gattii, remains responsible for considerable morbidity and mortality despite standard medical care. Current therapeutic options are limited to Amphotericin B, azoles and 5 flucytosine. However, this organism has numerous well-characterized virulence mechanisms that are amenable to pharmacological interference and are thus potential therapeutic targets. Here, we discuss existing approved antifungal drugs, resistance mechanisms to these drugs and non-standard antifungal drugs that have potential in treatment of cryptococcosis, including immunomodulatory strategies that synergize with antifungal drugs, such as cytokine administration or monoclonal antibodies. Finally, we summarize attempts to target well-described virulence factors of Cryptococcus, the capsule or fungal melanin. This review emphasizes the pressing need for new therapeutic alternatives for cryptococcosis. PMID- 26990052 TI - Opioids and cancer: friend or foe? AB - PURPOSE OF REVIEW: Most cancer patients experience pain and many will require opioids. However, the effects of opioids on cancer progression, metastasis, and recurrence is increasingly being questioned. There is evidence that opioids affect immune system function, angiogenesis, apoptosis, and invasion in a potentially deleterious manner. This review will examine the preclinical and clinical evidence. RECENT FINDINGS: Recent clinical data have struggled to find robust evidence that opioids promote cancer progression. Although most study has involved morphine, differential effects of other opioids on immune function and cancer are revealing a more complex picture. SUMMARY: Although there is a biologically plausible story, evidence for the action of opioids on cancer is mixed. Indeed, it may even be that in the chronic setting morphine has a beneficial effect on outcome in certain cancer types. This review critically examines and evaluates the evidence for the action of opioids on the processes involved in cancer progression. In the light of the uncertainty of opioid effect on cancer, any decision making should be tempered by knowing that stress and pain undoubtedly contribute to cancer progression. PMID- 26990053 TI - Comparison of preoperative adaptive enlargement of the contralateral normal kidney in patients nephrectomized for benign non-functioning kidney versus renal cell carcinoma. AB - OBJECTIVES: To investigate the potential effects of preoperative volumetric compensation of the contralateral normal kidney on renal function after simple nephrectomy or radical nephrectomy. METHODS: A total of 306 patients (80 simple nephrectomy patients and 226 radical nephrectomy patients) with 1:3 propensity score matching were included between October 1996 and December 2013. Preoperative three-dimensional kidney volume was estimated from computed tomography images using a specialized volumetric program. Glomerular filtration rate assessed using the Chronic Kidney Disease Epidemiology Collaboration equations was checked preoperatively, 1 week, 3 months and 1 year after nephrectomy. RESULTS: Preoperative mean Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate was 76.5 mL/min/1.73 m(2) in the simple nephrectomy group and 89.2 mL/min/1.73 m(2) in the radical nephrectomy group. In simple nephrectomy patients, mean Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate showed a stable pattern up to 3 months (75.5 mL/min/1.73 m(2) at 7 days and 76.2 mL/min/1.73 m(2) at 3 months), and decreased slightly to 72.6 mL/min/1.73 m(2) at 1 year. However, in radical nephrectomy patients, mean Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate decreased immediately to 63.4 mL/min/1.73 m(2) at 7 days after surgery, and then increased gradually to 64.6 mL/min/1.73 m(2) at 3 months and 65.9 mL/min/1.73 m(2) at 1 year. Preoperative mean contralateral normal kidney volume was 225.7 mL in the simple nephrectomy group and 180.1 mL in the radical nephrectomy group (P < 0.001). The contralateral normal kidney volume to total normal kidney volume ratio was 0.74 in the simple nephrectomy group and 0.51 in the radical nephrectomy group (P < 0.001). CONCLUSIONS: Preoperative volumetric compensation of the contralateral normal kidney is important to maintain postoperative renal function in patients undergoing nephrectomy. PMID- 26990051 TI - Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. AB - OBJECTIVE: Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder (BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. METHODS: Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, PsychINFO, and Clinicaltrials.gov databases. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences (SMDs) compared with standard therapy alone. RESULTS: Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was -0.40 (95% confidence interval -0.14 to -0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low (I2 = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. CONCLUSIONS: Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis. PMID- 26990054 TI - 40-Hz Sinusoidal Auditory Steady-State Response and Tone Burst Auditory Brainstem Response Using a Kalman Filter to Determine Thresholds Pre- and Post-Myringotomy With Grommet Tube in Children With Mild, Low-Frequency Conductive Hearing Loss. AB - PURPOSE: Accurate estimation of mild, low-frequency hearing loss is difficult in young children. This study aimed to determine the accuracy of 40-Hz sinusoidal auditory steady-state response (sASSR) compared with tone burst auditory brainstem response (TB-ABR) to detect mild, low-frequency hearing loss in children with otitis media with effusion and to measure postoperative thresholds. METHODS: Thresholds at 500 and 4000 Hz were measured behaviorally and electrophysiologically using TB-ABR and 40-Hz sASSR with a Kalman filter in 26 children with otitis media with effusion. Recording was conducted preoperatively and postoperatively while children were actively awake. Repeated measures mixed analyses of variance were conducted to determine effects among measures and the two test frequencies. RESULTS: Both 40-Hz sASSR and TB-ABR accurately detected preoperative and postoperative thresholds and were within 5-10 dB of the behavioral thresholds at 4000 Hz. At 500 Hz, the mean 40-Hz sASSR threshold was only 5 dB above the behavioral thresholds and 18 dB better than the 500-Hz ABR threshold. Positive correlations were found but not between 40-sASSR and TB-ABR at 500 Hz. Also, the interrater judgment of the response was better for sASSR (89%) than TB-ABR (83%). CONCLUSION: The 40-Hz sASSR is more accurate than TB-ABR in determining a mild, low-frequency threshold. PMID- 26990055 TI - IgG4-Related Disease: Retrospective Analysis of One Hundred Sixty-Six Patients. AB - OBJECTIVE: To investigate clinical and pathologic aspects of IgG4-related disease (IgG4-RD) in non-Asian populations. METHODS: We conducted a retrospective review of the medical records of patients with IgG4-RD who presented to an academic medical center from January 1994 to September 2012. RESULTS: Among 166 patients identified, the median age at diagnosis was 61 years (interquartile range [IQR] 49-70 years), 75% were male, and 80% were white. The median number of organs involved was 2 (IQR 2-3). When organs were grouped according to anatomic system, the hepatopancreaticobiliary system was most commonly involved (77%). The median highest serum IgG4 level during the clinical course was 215 mg/dl (IQR 122-466). Forty-three patients (26%) had a normal serum IgG4 level. Seventy-nine pathology specimens were available for immunostaining. The median number of IgG4+ cells was 37 (IQR 25-82) per high-power field, with an IgG4+:IgG+ ratio of 0.50 (IQR 0.32 0.68). Among 151 patients who received medical therapy, 72 (48%) received steroid sparing agents because of relapse, recurrence, or corticosteroid intolerance. Of the 66 patients who were newly diagnosed, started on corticosteroid monotherapy as the initial treatment, and followed up at our institution, 30 (45%) experienced relapse or recurrence despite an initial favorable response. The number of organs involved had a significant impact on time to relapse or recurrence, with a hazard ratio of 1.48 (95% confidence interval [95% CI] 1.12 1.93) (P < 0.01) in multivariate analysis. The standardized incidence ratio of malignancy was 4.5 (95% CI 1.5-7.5). CONCLUSION: IgG4-RD is a multisystem disorder that commonly affects older men and has a propensity for relapse, recurrence, and malignancy. PMID- 26990056 TI - Fibrous tether of the distal femur produced unilateral genu valgus with subsequent patellar dislocation: case report and review of the literature. AB - Fibrous tether at the distal femur is a rare condition that causes angular deformity of the lower extremity; only 18 cases have been reported previously. We report the case of a 2-year-old boy presenting with unilateral genu valgus. The patient had a subsequent lateral patellar dislocation, 1 year after surgical correction. A second surgery was performed to correct this patellar dislocation. Intraoperative finding indicated contracted lateral patellar retinaculum. To the best of our knowledge, this is the first report of such a finding. The natural history is still not understood. At the 6-month-follow-up visit, the patient still has good results without recurrent patellar dislocation or angular deformity. We also review the literature in terms of proper treatment and results of treatment. PMID- 26990057 TI - Minimally invasive, iliac crest-sparing approach for pelvic osteotomies in children. AB - The aim of this article is to describe a minimally invasive iliac crest-sparing approach (ICSA) allowing common iliac osteotomies in children. The ICSA was used for 98 hips in 72 consecutive patients who underwent a pelvic osteotomy. The mean follow-up duration ranged from 3 to 7 years. Skin incision ranged from 3 to 5.5 cm. Displacement of the distal osteotomy fragment was easy and without tension. The duration of surgery varied from 50 min in the beginning of our experience to 20-25 min for the last cases of the series. In conclusion, the ICSA fulfills all the criteria of minimally invasive surgery. PMID- 26990058 TI - Trends in the volume of operative treatment of midshaft clavicle fractures in children and adolescents: a retrospective, 12-year, single-institution analysis. AB - The purpose of this study was to examine institutional trends in the volume of clavicle fractures in children and adolescents. Medical records were retrospectively reviewed to identify patients aged 10-18 years treated for a clavicle fracture between 1999 and 2011 at a single tertiary-care pediatric hospital. There were significant increases in the number of clavicle fractures seen annually, of midshaft clavicle fractures, and of midshaft clavicle fractures treated operatively. The percentage of midshaft clavicle fractures treated with fixation also increased significantly. The volumes of clavicle fractures and midshaft clavicle fractures treated operatively appear to be increasing. Despite a lack of evidence-based support, the frequency of fixation of midshaft clavicle fractures appear to be increasing in the pediatric population. PMID- 26990059 TI - Iliac wing osteotomy for the closure of pelvis in the treatment of bladder exstrophy in the neonate. AB - Classic bladder exstrophy is a rare disorder involving an externalized bladder through an associated pelvic diastasis. Difficulty of closure of pelvic diastasis is often encountered following urological reconstruction. Traditionally, an anterior innominate osteotomy is performed to increase pelvic volume, allowing closure of the rudimentary pubic symphysis and anatomical reduction of pelvic contents; however, this procedure can be technically difficult and has associated morbidity. We describe a novel technique of bilateral iliac wing osteotomies to achieve the same function that has not been described previously in the literature. PMID- 26990060 TI - Treatment dilemma in multiple metatarsal fractures: when to operate? AB - Fractures of multiple metatarsals in the pediatric population are uncommon; however, indications for surgical treatment have not been delineated. The aim of this study was to review multiple metatarsal fractures to help refine surgical indications. A total of 98 patients had multiple metatarsal fractures; displacement greater than 10% shaft width (displaced) was encountered in 33 (34.0%) patients. Fifteen patients had displacement of more than 75% shaft width of one metatarsal. Patients older than 14 years of age were more likely to have surgery for their injury (52.6%) than those younger than 14 years of age (3.7%) (P<0.0001). Younger patients and those with less than 75% displacement should be considered for nonoperative care. LEVELS OF EVIDENCE: Level IV. PMID- 26990061 TI - Cancer Cell Internalization of Gold Nanostars Impacts Their Photothermal Efficiency In Vitro and In Vivo: Toward a Plasmonic Thermal Fingerprint in Tumoral Environment. AB - Gold nanoparticles are prime candidates for cancer thermotherapy. However, while the ultimate target for nanoparticle-mediated photothermal therapy is the cancer cell, heating performance has not previously been evaluated in the tumoral environment. A systematic investigation of gold nanostar heat-generating efficiency in situ is presented: not only in cancer cells in vitro but also after intratumoral injection in vivo. It is demonstrated that (i) in aqueous dispersion, heat generation is governed by particle size and exciting laser wavelength; (ii) in cancer cells in vitro, heat generation is still very efficient, but irrespective of both particle size and laser wavelength; and (iii) heat generation by nanostars injected into tumors in vivo evolves with time, as the nanostars are trafficked from the extracellular matrix into endosomes. The plasmonic heating response thus serves as a signature of nanoparticle internalization in cells, bringing the ultimate goal of nanoparticle-mediated photothermal therapy a step closer. PMID- 26990063 TI - Short-Chain Fatty Acid Acetate Stimulates Adipogenesis and Mitochondrial Biogenesis via GPR43 in Brown Adipocytes. AB - Short-chain fatty acids play crucial roles in a range of physiological functions. However, the effects of short-chain fatty acids on brown adipose tissue have not been fully investigated. We examined the role of acetate, a short-chain fatty acid formed by fermentation in the gut, in the regulation of brown adipocyte metabolism. Our results show that acetate up-regulates adipocyte protein 2, peroxisomal proliferator-activated receptor-gamma coactivator-1alpha, and uncoupling protein-1 expression and affects the morphological changes of brown adipocytes during adipogenesis. Moreover, an increase in mitochondrial biogenesis was observed after acetate treatment. Acetate also elicited the activation of ERK and cAMP response element-binding protein, and these responses were sensitive to G(i/o)-type G protein inactivator, Gbetagamma-subunit inhibitor, phospholipase C inhibitor, and MAPK kinase inhibitor, indicating a role for the G(i/o)betagamma/phospholipase C/protein kinase C/MAPK kinase signaling pathway in these responses. These effects of acetate were mimicked by treatment with 4 chloro-alpha-(1-methylethyl)-N-2-thiazolylbenzeneacetamide, a synthetic G protein coupled receptor 43 (GPR43) agonist and were impaired in GPR43 knockdown cells. Taken together, our results indicate that acetate may have important physiological roles in brown adipocytes through the activation of GPR43. PMID- 26990062 TI - Pgrmc1/BDNF Signaling Plays a Critical Role in Mediating Glia-Neuron Cross Talk. AB - Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membrane-associated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted. PMID- 26990064 TI - Pasireotide Therapy of Multiple Endocrine Neoplasia Type 1-Associated Neuroendocrine Tumors in Female Mice Deleted for an Men1 Allele Improves Survival and Reduces Tumor Progression. AB - Pasireotide, a somatostatin analog, is reported to have anti-proliferative effects in neuroendocrine tumors (NETs). We therefore assessed the efficacy of pasireotide for treating pancreatic and pituitary NETs that develop in a mouse model of multiple endocrine neoplasia type 1 (MEN1). Men1(+/-) mice were treated from age 12 mo with 40 mg/kg pasireotide long-acting release formulation, or PBS, intramuscularly monthly for 9 mo. The Men1(+/-) mice had magnetic resonance imaging at 12 and 21 mo, and from 20 mo oral 5-bromo-2-deoxyuridine for 1 mo, to assess tumor development and proliferation, respectively. NETs were collected at age 21 mo, and proliferation and apoptosis assessed by immunohistochemistry and TUNEL assays, respectively. Pasireotide-treated Men1(+/-) mice had increased survival (pasireotide, 80.9% vs PBS, 65.2%; P < .05), with fewer mice developing pancreatic NETs (pasireotide, 86.9% vs PBS, 96.9%; P < .05) and smaller increases in pituitary NET volumes (pre-treated vs post-treated, 0.803 +/- 0.058 mm(3) vs 2.872 +/- 0.728 mm(3) [pasireotide] compared with 0.844 +/- 0.066 mm(3) vs 8.847 +/-1.948 mm(3) [PBS]; P < .01). In addition, pasireotide-treated mice had fewer pancreatic NETs compared with PBS-treated mice (2.36 +/- 0.25 vs 3.72 +/- 0.32, respectively; P < .001), with decreased proliferation in pancreatic NETs (pasireotide, 0.35 +/- 0.03% vs PBS, 0.78 +/- 0.08%; P < .0001) and pituitary NETs (pasireotide, 0.73 +/-0.07% vs PBS, 1.81 +/- 0.15%; P < .0001), but increased apoptosis in pancreatic NETs (pasireotide, 0.42 +/- 0.05% vs PBS, 0.19 +/- 0.03%; P < .001) and pituitary NETs (pasireotide, 14.75 +/- 1.58% vs PBS, 2.35 +/- 0.44%; P < .001). Thus, pasireotide increased survival and inhibited pancreatic and pituitary NET growth, thereby indicating its potential as an anti proliferative and pro-apoptotic therapy. PMID- 26990066 TI - Estrogen Regulation of Fetal Adrenal Cortical Zone-Specific Development in the Nonhuman Primate Impacts Adrenal Production of Androgen and Cortisol and Response to ACTH in Females in Adulthood. AB - We showed that the volume of the fetal zone of the fetal adrenal gland and serum dehydroepiandrosterone sulfate (DHAS) levels at term were increased in baboons in which estradiol levels were suppressed by treatment with aromatase inhibitor 4,4 [1,2,3-triazol-1yl-methylene] bis-benzonitrite (letrozole). The fetal zone remodels postnatally into the reticular zone and DHAS production, and serum levels decline with age. Therefore, we determined whether the trajectory of reticular zone DHAS secretion and response to ACTH were altered in offspring deprived of estrogen in utero. Female offspring were delivered to baboons untreated or treated daily throughout the second half of gestation with letrozole (estradiol reduced >95%) or letrozole plus estradiol and cortisol and DHAS determined in blood samples obtained bimonthly between 4 and 125 months and after iv bolus of ACTH. The slope/rate of decline in serum DHAS with advancing age was greater (P < .01) in letrozole-treated (-0.54 +/- 0.005) than untreated (-0.32 +/ 0.003) baboons and partially restored by letrozole-estradiol (-0.43 +/- 0.004). Serum cortisol was similar and relatively constant in all offspring. Moreover, in letrozole-treated offspring, serum DHAS at 61-66, 67-95, and 96-125 months were lower (P < .05), and cortisol to DHAS ratio was greater (P < .05) than in untreated offspring. ACTH at high level increased cortisol and DHAS in untreated baboons and cortisol but not DHAS in letrozole-treated offspring. We propose that postnatal development of the primate adrenal cortex, including the decline in reticular zone DHAS production, response to ACTH and maintenance of cortisol to DHAS ratio with advancing age is modulated by exposure of the fetal adrenal to estradiol. PMID- 26990067 TI - Photocatalysis-Induced Renewable Field-Effect Transistor for Protein Detection. AB - The field-effect transistor (FET) biosensor has attracted extensive attentions, due to its unique features in detecting various biomolecules with high sensitivity and selectivity. However, currently used FET biosensors obtaining from expensive and elaborate micro/nanofabrication are always disposable because the analyte cannot be efficiently removed after detection. In this work, we established a photocatalysis-induced renewable graphene-FET (G-FET) biosensor for protein detection, by layer-to-layer assembling reduced graphene oxide (RGO) and RGO-encapsulated TiO2 composites to form a sandwiching RGO@TiO2 structure on a prefabricated FET sensor surface. After immobilization of anti-D-Dimer on the graphene surface, sensitive detection of D-Dimer was achieved with the detection limits of 10 pg/mL in PBS and 100 pg/mL in serum, respectively. Notably, renewal of the FET biosensor for recycling measurements was significantly realized by photocatalytically cleaning the substances on the graphene surface. This work demonstrates for the first time the development and application of photocatalytically renewable G-FET biosensor, paving a new way for G-FET sensor toward a plethora of diverse applications. PMID- 26990065 TI - Planar Cell Polarity (PCP) Protein Vangl2 Regulates Ectoplasmic Specialization Dynamics via Its Effects on Actin Microfilaments in the Testes of Male Rats. AB - Planar cell polarity (PCP) proteins confer polarization of a field of cells (eg, elongating/elongated spermatids) within the plane of an epithelium such as the seminiferous epithelium of the tubule during spermatogenesis. In adult rat testes, Sertoli and germ cells were found to express PCP core proteins (eg, Van Gogh-like 2 [Vangl2]), effectors, ligands, and signaling proteins. Vangl2 expressed predominantly by Sertoli cells was localized at the testis-specific, actin-rich ectoplasmic specialization (ES) at the Sertoli-spermatid interface in the adluminal compartment and also Sertoli-Sertoli interface at the blood-testis barrier (BTB) and structurally interacted with actin, N-cadherin, and another PCP/polarity protein Scribble. Vangl2 knockdown (KD) by RNA interference in Sertoli cells cultured in vitro with an established tight junction-permeability barrier led to BTB tightening, whereas its overexpression using a full-length cDNA construct perturbed the barrier function. These changes were mediated through an alteration on the organization actin microfilaments at the ES in Sertoli cells, involving actin-regulatory proteins, epidermal growth factor receptor pathway substrate 8, actin-related protein 3, and Scribble, which in turn affected the function of adhesion protein complexes at the ES during the epithelial cycle of spermatogenesis. Using Polyplus in vivo-jetPEI reagent as a transfection medium to silence Vangl2 in the testis in vivo by RNA interference with high efficacy, Vangl2 KD led to changes in F-actin organization at the ES in the epithelium, impeding spermatid and phagosome transport and spermatid polarity, meiosis, and BTB dynamics. For instance, step 19 spermatids remained embedded in the epithelium alongside with step 9 and 10 spermatids in stages IX-X tubules. In summary, the PCP protein Vangl2 is an ES regulator through its effects on actin microfilaments in the testis. PMID- 26990068 TI - Incidence and Risk Factors for Infection When Teicoplanin Is Included for Prophylaxis in Patients with Hip Fracture. AB - BACKGROUND: Surgical site infection (SSI) rate after surgery for hip fracture is about 4%. The aim of the present study was to review the efficacy of dual prophylaxis using teicoplanin plus cefuroxime and risk factors for SSI. PATIENTS: Operations for hip fracture from 2012 to 2013 were retrospectively reviewed. Relevant information was gathered: Demographics, comorbidities, ASA score, laterality, type of fracture, type of surgery, d from admission to surgery, length of surgery, hemoglobin value at admission, urinary or respiratory infections, and the need for pre-operative, intra-operative, and post-operative red blood cell (RBC) transfusion. Prophylaxis consisted of cefuroxime and teicoplanin during the induction of anesthesia. U.S. Centers for Disease Control and Prevention (CDC) criteria for superficial and deep SSI were applied. Univariate and multivariable analysis were performed. RESULTS: Six hundred fifty seven patients were included in the study. Thirteen (2.0%) SSI were identified, six superficial (0.9%), and seven deep (1.1%). Staphylococcus aureus was isolated in two infections (one superficial and one deep). The SSI rate was 2.4% in intra medullary nails (n = 334), 1.4% in prostheses (n = 211), and 1.8% in other synthesis (n = 112). Parameters independently associated with SSI were: Intra operative RBC transfusion (OR: 11.6, p = 0.002), length of surgery >120 min (OR: 4.5, p = 0.02), and having a urinary infection (OR: 4.28, p = 0.02). CONCLUSION: Dual prophylaxis including cefuroxime and teicoplanin was associated with a 2% rate of SSI. Staphylococcus aureus caused only two SSIs. Reducing SSI is of utmost importance for patients' quality of life and to avoid additional cost of surgical procedures. Therefore, more experience with dual prophylaxis is needed to confirm our results. PMID- 26990069 TI - Resolution of Intrathecal Hydromorphone or Morphine-induced Peripheral Edema by Opioid Rotation to Fentanyl: A Case Series. AB - INTRODUCTION: Intrathecal therapy [IT] has become an important modality for treatment of intractable cancer and noncancer pain although adverse events limit its effectiveness. OBJECTIVE: The purpose of this case series was to report and discuss the lower limb edema from IT hydromorphone and morphine therapy and its resolution or nonrecurrence upon rotating the IT solution to fentanyl. METHODS: Case series. RESULTS: Five patients, 4 women and 1 man, 55 to 67 years old implanted with IT delivery device systems [IDDS] were treated with continuous infusion of hydromorphone [4 subjects] at 95 +/- 40 mcg/24 hours and morphine [1 subject] at 0.67 mg/24 hours. They developed peripheral edema of the lower extremities at an average of 4.2 months [mean, range 1 to 8 months] after implant. In 4 subjects, peripheral edema resolved by changing the IT agent to fentanyl. The mean time for complete resolution of edema was 50 +/- 20 days while patients were treated with continuous infusion of fentanyl. It should be noted that all patients were receiving bupivacaine in addition to the IT opioid. In one subject, infusion of IT saline resulted in faster resolution of peripheral edema. CONCLUSION: Peripheral lower extremity edema may occur in patients treated with IT infusion of hydromorphone or morphine, even at low doses. This report presents, to the best of our knowledge, the first case series describing the benefit of IT opioid rotation to fentanyl in alleviating challenging lower extremity edema from IT hydromorphone and morphine. PMID- 26990070 TI - Changes in the quality of superchilled rabbit meat stored at different temperatures. AB - This work studied the effects of a superchilling process at two different temperatures on the shelf life and selected quality parameters of rabbit meat. As the storage time increased, the rates at which the total aerobic count, total volatile basic nitrogen, thiobarbituric acid-reactive substances and pH value increased were significantly lower in superchilled rabbit meat stored at -4 degrees C compared to those in rabbit meat stored at -2.5 degrees C and 4 degrees C. SDS-PAGE analysis indicated that the decrease in storage temperature could significantly reduce the degree of protein degradation. The lightness, redness, shear force, the integrity of muscle microstructure and water holding capacity decreased with increasing storage time. Compared with the samples frozen at -18 degrees C, superchilled rabbit meat shows a marked reduction in microstructure deterioration. These results suggest that shelf life of good-quality rabbit meat was 20d under superchilling at -2.5 degrees C and at least 36d under superchilling at -4 degrees C, compared with less than 6d under traditional chilled storage. PMID- 26990071 TI - Experimental and theoretical analyses of the age-dependent large-strain behavior of Sylgard 184 (10:1) silicone elastomer. AB - The commercial polydimethysiloxane elastomer Sylgard((r)) 184 with mixing ratio 10:1 is in wide use for biomedical research or fundamental studies of mechanobiology. In this paper, a comprehensive study of the large strain mechanical behavior of this material under multiaxial monotonic and cyclic loads, and its change during the first 26 days after preparation is reported. The equibiaxial stress response studied in inflation experiments reveals a much stiffer and more nonlinear response compared to the uniaxial and pure shear characteristics. The polymer revealed remarkably elastic behavior, in particular, very little dependence on strain rates between 0.3%/s and 11%/s, and on the strain history in cyclic experiments. On the other hand, both the small-strain and large strain nonlinear mechanical characteristics of the elastomer are changing with sample age and the results suggest that this process has not ceased after 26 days. A recent re-interpretation of the well-known Ogden model for incompressible rubber-like materials was applied to rationalize the results and accurate agreement was obtained with the experimental data over all testing configurations and testing times. The change of a single parameter in this model is shown to govern the evolution of the nonlinear material characteristics with sample age, attributed to a continuation of the cross-linking process. Based on a kinetic relation to account for this process over time, the model provided successful predictions of the material behavior even after more than one year. PMID- 26990072 TI - Contact fatigue of human enamel: Experiments, mechanisms and modeling. AB - Cyclic contact between natural tooth structure and engineered ceramics is increasingly common. Fatigue of the enamel due to cyclic contact is rarely considered. The objectives of this investigation were to evaluate the fatigue behavior of human enamel by cyclic contact, and to assess the extent of damage over clinically relevant conditions. Cyclic contact experiments were conducted using the crowns of caries-free molars obtained from young donors. The cuspal locations were polished flat and subjected to cyclic contact with a spherical indenter of alumina at 2Hz. The progression of damage was monitored through the evolution in contact displacement, changes in the contact hysteresis and characteristics of the fracture pattern. The contact fatigue life diagram exhibited a decrease in cycles to failure with increasing cyclic load magnitude. Two distinct trends were identified, which corresponded to the development and propagation of a combination of cylindrical and radial cracks. Under contact loads of less than 400N, enamel rod decussation resisted the growth of subsurface cracks. However, at greater loads the damage progressed rapidly and accelerated fatigue failure. Overall, cyclic contact between ceramic appliances and natural tooth structure causes fatigue of the enamel. The extent of damage is dependent on the magnitude of cyclic stress and the ability of the decussation to arrest the fatigue damage. PMID- 26990073 TI - CABCOCO1, a novel coiled-coil protein With calcium-binding activity, is localized in the sperm flagellum. AB - The gene 1700040L02Rik (GenBank accession number NM_028491, NP_082767.1) was selected by in silico screening as candidate that encodes a calcium-binding protein in sperm from a database of predicted mouse cilia-related genes. The predicted amino acid sequence revealed the presence of coiled-coil domain at the C-terminus and a CLAMP motif containing a leucine zipper domain in the middle of the protein. Assessment of a recombinant version of this protein by Stains-all and ruthenium red staining and by direct measurement of terbium binding revealed its calcium-binding activities. We therefore named this protein CABCOCO1 for calcium-binding coiled-coil protein-1. Immunohistochemical analyses showed its localization in spermatogenic cells of mouse testis. CABCOCO1 was first observed in the cytoplasm of murine spermatocytes, concentrated around centrioles of spermatids and co-localized with the centrosomal protein pericentrin. During the stage when centrosome number is reduced, CABCOCO1 relocalized to the murine sperm flagellum. On the other hand, in porcine sperm, whose proximal centriole remains intact while the distal centriole degenerates during spermiogenesis, CABCOCO1 localized both in the basal body and the flagellum. These results suggested that CABCOCO1 is involved in the control of sperm flagellar movement. Mol. Reprod. Dev. 83: 912-926, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 26990074 TI - Inferring the chemical form of 137Cs deposited by the Fukushima Dai-ichi Nuclear Power Plant accident by measuring (137)Cs incorporated into needle leaves and male cones of Japanese cedar trees. AB - We hypothesized that the water-soluble (ionic) and water-insoluble (stable) radiocesium from the initial fallout of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident was distributed in various proportions in the surrounding areas and that this distribution was reflected in the trees that suffered deposition from the initial fallout. This study attempted to evaluate local variations in the chemical form of (137)Cs derived from the initial fallout of the FDNPP accident and whether its chemical form affected the radiocesium concentration in the tissues currently growing in trees, even after the initial fallout ceased. For these estimations, the ratio between the (137)Cs concentration in Cryptomeria japonica needle leaves in the tree crown, which existed before the FDNPP accident and subsequently directly exposed to the initial fallout ((137)Cs pre-accident N), and the amount of (137)Cs in the initial fallout itself ((137)Cs fallout) was determined ((137)Cs pre-accident N/(137)Cs fallout) at 66 sites. In addition, the (137)Cs ratios between the male cones produced in 2012 ((137)Cs male cone) and needle leaves that had elongated in the spring of 2011 ((137)Cs 2011N) was determined at 82 sites ((137)Cs male cone/(137) Cs 2011N). Most of the sites with lower (137)Cs pre-accident N /(137)Cs fallout ratios were distributed in eastern Fukushima, relatively close to the Pacific Ocean coastline. Lower (137)Cs pre-accident N/(137)Cs fallout and higher (137)Cs malecone/(137)Cs 2011N were found to be associated with higher proportions of (137)Cs in ionic forms. These observations are consistent with the hypothesis, and likely reflect regional variations in the chemical form of the deposited radiocesium. PMID- 26990075 TI - Poultry litter and the environment: Physiochemical properties of litter and soil during successive flock rotations and after remote site deposition. AB - The U.S. broiler meat market has grown over the past 16 years and destinations for U.S. broiler meat exports expanded to over 150 countries. This market opportunity has spurred a corresponding increase in industrialized poultry production, which due to the confined space in which high numbers of animals are housed, risks accumulating nutrients and pollutants. The purpose of this research was to determine the level of pollutants within poultry litter and the underlying soil within a production facility; and to explore the impact of spent litter deposition into the environment. The study follows a production facility for the first 2.5 years of production. It monitors the effects of successive flocks and management practices on 15 physiochemical parameters: Ca, Cu, electrical conductivity, Fe, K, Mg, Mn, moisture, Na, NO3(-)/N, organic matter, P, pH, S, and Zn. Litter samples were collected in-house, after clean-outs and during stockpiling. The soil before house placement, after the clean-outs and following litter stockpiling was monitored. Management practices markedly altered the physiochemical profiles of the litter in-house. A canonical discriminant analysis was used to describe the relationship between the parameters and sampling times. The litter profiles grouped into five clusters corresponding to time and management practices. The soil in-house exhibited mean increases in all physiochemical parameters (2-297 fold) except Fe, Mg, %M, and pH. The spent litter was followed after deposition onto a field for use as fertilizer. After 20 weeks, the soil beneath the litter exhibited increases in EC, Cu, K, Na, NO3( )/N, %OM, P, S and Zn; while %M decreased. Understanding the impacts of industrialized poultry farms on the environment is vital as the cumulative ecological impact of this land usage could be substantial if not properly managed to reduce the risk of potential pollutant infiltration into the environment. PMID- 26990076 TI - EMA-qPCR to monitor the efficiency of a closed-coupled solar pasteurization system in reducing Legionella contamination of roof-harvested rainwater. AB - Solar pasteurization is effective in reducing the level of indicator organisms in stored rainwater to within drinking water standards. However, Legionella spp. were detected at temperatures exceeding the recommended pasteurization temperatures using polymerase chain reaction assays. The aim of the current study was thus to apply EMA quantitative polymerase chain reaction (EMA-qPCR) to determine whether the Legionella spp. detected were intact cells and therefore possibly viable at pasteurization temperatures >70 degrees C. The BacTiter-GloTM Microbial Cell Viability Assay was also used to detect the presence of ATP in the tested samples, as ATP indicates the presence of metabolically active cells. Chemical analysis also indicated that all anions and cations were within the respective drinking water guidelines, with the exception of iron (mean: 186.76 MUg/L) and aluminium (mean: 188.13 MUg/L), which were detected in the pasteurized tank water samples at levels exceeding recommended guidelines. The BacTiter-GloTM Microbial Cell Viability Assay indicated the presence of viable cells for all pasteurized temperatures tested, with the percentage of ATP (in the form of relative light units) decreasing with increasing temperature [70-79 degrees C (96.7%); 80- 89 degrees C (99.2%); 90-95 degrees C (99.7%)]. EMA-qPCR then indicated that while solar pasteurization significantly reduced (p<0.05) the genomic copy numbers of intact Legionella cells in the pasteurized tank water (~99%), no significant difference (p>0.05) in the mean copy numbers was detected with an increase in the pasteurization temperature, with 6 * 10(3) genomic copies/mL DNA sample obtained at 95 degrees C. As intact Legionella cells were detected in the pasteurized tank water samples, quantitative microbial risk assessment studies need to be conducted to determine the potential health risk associated with using the water for domestic purposes. PMID- 26990077 TI - First results of a simultaneous measurement of tritium and (14)C in an ultra-low background proportional counter for environmental sources of methane. AB - Simultaneous measurement of tritium and (14)C would provide an added tool for tracing organic compounds through environmental systems and is possible via beta energy spectroscopy of sample-derived methane in internal-source gas proportional counters. Since the mid-1960's atmospheric tritium and (14)C have fallen dramatically as the isotopic injections from aboveground nuclear testing have been diluted into the ocean and biosphere. In this work, the feasibility of simultaneous tritium and (14)C measurements via proportional counters is revisited in light of significant changes in both the atmospheric and biosphere isotopics and the development of new ultra-low-background gas proportional counting capabilities for small samples (roughly 50 cc methane). A Geant4 Monte Carlo model of a Pacific Northwest National Laboratory (PNNL) proportional counter response to tritium and (14)C is used to analyze small samples of two different methane sources to illustrate the range of applicability of contemporary simultaneous measurements and their limitations. Because the two methane sources examined were not sample size limited, we could compare the small sample measurements performed at PNNL with analysis of larger samples performed at a commercial laboratory. These first results show that the dual-isotope simultaneous measurement is well matched for methane samples that are atmospheric or have an elevated source of tritium (i.e. landfill gas). However, for samples with low/modern tritium isotopics (rainwater), commercial separation and counting is a better fit. PMID- 26990078 TI - Cardiomyocyte loss is not required for the progression of left ventricular hypertrophy induced by pressure overload in female mice. AB - Left ventricular (LV) hypertrophy in response to hypertension and increased afterload frequently progresses to heart failure. It is under debate whether the loss of cardiomyocytes contributes to this transition. To address this question, female C57BL/6 wild-type mice were subjected to transverse aortic constriction (TAC) and developed compensated LV hypertrophy after 1 week, which progressed to heart failure characterized by reduced ejection fraction and pulmonary congestion 4 weeks post-TAC. Quantitative, design-based stereology methods were used to estimate number and mean volume of LV cardiomyocytes. DNA strand breaks were visualized using the TUNEL method 6 weeks post-TAC to quantify the number of apoptotic cell nuclei. The volume of the LV myocardium as well as the cardiomyocyte mean volume increased progressively after TAC. In contrast, the number of LV cardiomyocytes remained constant 1 and 4 weeks post-TAC in comparison to sham-operated mice. Moreover, there was no significant difference in the number of cardiomyocyte nuclei stained for DNA strand breaks at 6 weeks post-TAC. It was concluded that the loss of cardiomyocytes is not required for the transition from compensated hypertrophy to heart failure induced by TAC in the female murine heart. PMID- 26990080 TI - Li3V2(PO4)3 encapsulated flexible free-standing nanofabric cathodes for fast charging and long life-cycle lithium-ion batteries. AB - Lithiated transition metal phosphates with large theoretical capacities have emerged as promising cathode materials for rechargeable lithium-ion batteries. However, the poor kinetic properties caused by their low intrinsic electronic and ionic conductivity greatly hinder their practical applications. In this work, we demonstrate a novel strategy to prepare monoclinic lithium vanadium phosphate nanoparticles implanted in carbon nanofibers as the cathodes of Li-ion cells with high capacity, flexibility, long cycle stability and significantly improved high rate performance. The composite nanofibers were obtained by electrospinning using polyacrylonitrile and Li3V2(PO4)3 nanoparticles, followed by annealing and coating with a thin layer of carbon by plasma enhanced chemical vapor deposition. The Li3V2(PO4)3 nanocrystals with the monoclinic phase were uniformly distributed in the composite nanofibers. The electrochemical performances of the as-prepared binder-free fibrous cathodes were characterized by potentiostatic and galvanostatic tests. At the rate of 0.5 C in the range of 3.0-4.3 V, the composite displayed an initial discharge capacity of 128 mA h g(-1) (96.2% of the theoretical capacity). A discharge capacity of 120 mA h g(-1) was observed even at a high rate of 10 C, and a capacity retention of 98.9% was maintained after 500 cycles at 5 C, indicating excellent high-rate capability and capacity retention. Compared to the control samples without a carbon outer-layer, the composite nanofibers with carbon coating demonstrated much better electrochemical performances. It indicates that the carbon coating can further protect the structural integrity of nanofabric electrodes during the charge/discharge processes without hindering the Li-ion mobility and also can prevent undesired side reactions with an electrolyte, thus greatly improving the rate performance and cyclic stability of the cathode. PMID- 26990079 TI - Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity. AB - BACKGROUND AND PURPOSE: Sphingosine1-phosphate (S1P) receptors mediate multiple events including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Stimulation of S1P1 receptors sequesters lymphocyte subsets in peripheral lymphoid organs, preventing their trafficking to inflamed tissue sites, modulating immunity. Targeting S1P receptors for treating autoimmune disease has been established in clinical studies with the non-selective S1P modulator, FTY720 (fingolimod, GilenyaTM). The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases. EXPERIMENTAL APPROACH: The specificity and potency of RPC1063 (ozanimod) was evaluated for all five S1P receptors, and its effect on cell surface S1P1 receptor expression, was characterized in vitro. The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6 trinitrobenzenesulfonic acid colitis and CD4(+) CD45RB(hi) T cell adoptive transfer colitis) was assessed. KEY RESULTS: RPC1063 was specific for S1P1 and S1P5 receptors, induced S1P1 receptor internalization and induced a reversible reduction in circulating B and CCR7(+) T lymphocytes in vivo. RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half-life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models. CONCLUSIONS AND IMPLICATIONS: S1P receptor selectivity, favourable PK properties and efficacy in three distinct disease models supports the clinical development of RPC1063 for the treatment of relapsing multiple sclerosis and inflammatory bowel disease, differentiates RPC1063 from other S1P receptor agonists, and could result in improved safety outcomes in the clinic. PMID- 26990082 TI - Exciton Brightening in Monolayer Phosphorene via Dimensionality Modification. AB - Exciton brightening in monolayer phosphorene is achieved via the dimensionality modification of excitons from quasi-1D to 0D. The luminescence quantum yield of 0D-like excitons is >33.6 times larger than that of quasi-1D free excitons. 2D phosphorene with quasi-1D free excitons and 0D-like excitons provides a unique platform to investigate the fundamental phenomena in the ideal 2D-1D-0D hybrid system. PMID- 26990081 TI - Synergistic effect of bioactive lipid and condition medium on cardiac differentiation of human mesenchymal stem cells from different tissues. AB - Human umbilical cord mesenchymal stem cells (hUCMSCs) and human adipose tissue mesenchymal stem cells (hATMSCs) have the potential to differentiate into cardiomyocytes, making them promising therapeutic candidates for treating damaged cardiac tissues. Currently, however, the differentiated cells induced from hUCMSCs or hATMSCs can hardly display functional characteristics similar to cardiomyocytes. In this study, we have investigated the effects of bioactive lipid sphingosine-1-phosphate (S1P) on cardiac differentiations of hUCMSCs and hATMSCs in condition medium composed of cardiac myocytes culture medium or 5 azacytidine. Cardiac differentiations were identified through immunofluorescence staining, and the results were observed with fluorescence microscopy and confocal microscopy. Synergistic effects of S1P and condition medium on cell viability were evaluated by MTT assays. Functional characteristics similar to cardiomyocytes were evaluated through detecting calcium transient. The differentiated hUCMSCs or hATMSCs in each group into cardiomyocytes showed positive expressions of cardiac specific proteins, including alpha-actin, connexin-43 and myosin heavy chain-6 (MYH-6). MTT assays showed that suitable differentiation time was 14 days and that the optimal concentration of S1P was 0.5 MUM. Moreover, incorporation of S1P and cardiac myocytes culture medium gave rise to calcium transients, an important marker for displaying in vivo electrophysiological properties. This feature was not observed in the S1P-5 azacytidine group, indicating the possible lack of cellular stimuli such as transforming growth factor-beta, TGF-beta. PMID- 26990083 TI - Synthesis and Properties of Endohedral Aza[60]fullerenes: H2O@C59N and H2@C59N as Their Dimers and Monomers. AB - The macroscopic-scale syntheses of the first endohedral aza[60]fullerenes X@C59N (X = H2O, H2) were achieved in two different ways: (1) synthesis from endohedral fullerene H2O@C60 as a starting material and (2) molecular surgical synthesis from a C59N precursor having a considerably small opening. In the neutral state of H2O@C59N, we expected the H-bonding interaction or repulsive N-O interaction between entrapped H2O and a nitrogen atom on the C59N cage. However, an attractive electrostatic N-O interaction was suggested from the results of variable temperature NMR, nuclear magnetic relaxation times (T1, T2), and density functional theory (DFT) calculations. Upon the reaction with acetone via cationic intermediate C59N(+), we found a difference in reaction rates between H2O@C59N and H2@C59N dimers (observed reaction rates: k'(H2O)/k'(H2) = 1.74 +/- 0.16). The DFT calculations showed thermal stabilization of C59N(+) by entrapped H2O through the electrostatic interaction. PMID- 26990085 TI - Human papillomavirus detection in a "Digital" age. PMID- 26990084 TI - A randomized controlled trial of cognitive behavioral therapy for ADHD in medication-treated adolescents. AB - OBJECTIVE: To test cognitive behavioral therapy (CBT) for persistent attention deficit hyperactivity disorder (ADHD) symptoms in a sample of medication-treated adolescents. METHODS: Forty-six adolescents (ages 14-18), with clinically significant ADHD symptoms despite stable medication treatment were randomly assigned to receive CBT for ADHD or wait list control in a cross-over design. Twenty-four were randomized to CBT, 22 to wait list, and 15 crossed-over from wait list to CBT. A blind independent evaluator (IE) rated symptom severity on the ADHD Current Symptom Scale, by adolescent and parent report, and rated each subject using the Clinical Global Impression Severity Scale (CGI), a global measure of distress and impairment. These assessments were performed at baseline, 4-months (post-CBT or post wait list), and 8-months (post-treatment for those originally assigned to the wait list condition and 4-month follow-up for those originally assigned to CBT). TRIAL REGISTRATION: http://clinicaltrials.gov/show/NCT01019252. RESULTS: Using all available data, mixed effects modeling, and pooling for the wait list cross-over, participants who received CBT received a mean score 10.93 lower on the IE-rated parent assessment of symptom severity (95% CI: -12.93, -8.93; p < .0001), 5.24 lower on the IE-rated adolescent assessment of symptom severity (95% CI: -7.21, -3.28; p < .0001), and 1.17 lower IE-rated CGI (95% CI: -1.39, -.94; p < .0001). Results were consistent across 100 multiple imputations (all p < .0001). There was a greater proportion of responders after CBT by parent (50% vs. 18%, p = .00) and adolescent (58% vs. 18% p = .02) report. CONCLUSIONS: This study demonstrates initial efficacy of CBT for adolescents with ADHD who continued to exhibit persistent symptoms despite medications. PMID- 26990086 TI - Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression. AB - Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO). Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3) and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling. PMID- 26990087 TI - Ultra-Rapid Vision in Birds. AB - Flying animals need to accurately detect, identify and track fast-moving objects and these behavioral requirements are likely to strongly select for abilities to resolve visual detail in time. However, evidence of highly elevated temporal acuity relative to non-flying animals has so far been confined to insects while it has been missing in birds. With behavioral experiments on three wild passerine species, blue tits, collared and pied flycatchers, we demonstrate temporal acuities of vision far exceeding predictions based on the sizes and metabolic rates of these birds. This implies a history of strong natural selection on temporal resolution. These birds can resolve alternating light-dark cycles at up to 145 Hz (average: 129, 127 and 137, respectively), which is ca. 50 Hz over the highest frequency shown in any other vertebrate. We argue that rapid vision should confer a selective advantage in many bird species that are ecologically similar to the three species examined in our study. Thus, rapid vision may be a more typical avian trait than the famously sharp vision found in birds of prey. PMID- 26990088 TI - The Multi-Scale Network Landscape of Collaboration. AB - Propelled by the increasing availability of large-scale high-quality data, advanced data modeling and analysis techniques are enabling many novel and significant scientific understanding of a wide range of complex social, natural, and technological systems. These developments also provide opportunities for studying cultural systems and phenomena--which can be said to refer to all products of human creativity and way of life. An important characteristic of a cultural product is that it does not exist in isolation from others, but forms an intricate web of connections on many levels. In the creation and dissemination of cultural products and artworks in particular, collaboration and communication of ideas play an essential role, which can be captured in the heterogeneous network of the creators and practitioners of art. In this paper we propose novel methods to analyze and uncover meaningful patterns from such a network using the network of western classical musicians constructed from a large-scale comprehensive Compact Disc recordings data. We characterize the complex patterns in the network landscape of collaboration between musicians across multiple scales ranging from the macroscopic to the mesoscopic and microscopic that represent the diversity of cultural styles and the individuality of the artists. PMID- 26990089 TI - Modelling Management Practices in Viticulture while Considering Resource Limitations: The Dhivine Model. AB - Many farming-system studies have investigated the design and evaluation of crop management practices with respect to economic performance and reduction in environmental impacts. In contrast, little research has been devoted to analysing these practices in terms of matching the recurrent context-dependent demand for resources (labour in particular) with those available on the farm. This paper presents Dhivine, a simulation model of operational management of grape production at the vineyard scale. Particular attention focuses on representing a flexible plan, which organises activities temporally, the resources available to the vineyard manager and the process of scheduling and executing the activities. The model relies on a generic production-system ontology used in several agricultural production domains. The types of investigations that the model supports are briefly illustrated. The enhanced realism of the production management situations simulated makes it possible to examine and understand properties of resource-constrained work-organisation strategies and possibilities for improving them. PMID- 26990091 TI - Inorganic and Total Arsenic Contents in Rice and Rice-Based Foods Consumed by a Potential Risk Subpopulation: Sportspeople. AB - One of the main routes of exposure to inorganic arsenic (i-As) in humans is food, especially rice and rice-based products. There are certain groups of consumers that could be highly exposed to i-As. Maximum levels of i-As have been issued for infants and young children by the European Union, but perhaps other groups are also at risk. Sportspeople could be one of those groups, due to their specific nutritional requirements, especially its high consumption of cereals, such as rice. Because of the well-known relationship between rice and i-As, the intake of i-As by sportspeople deserved especial attention and was estimated in Spain. This study demonstrated that rice-based products reached a maximum i-As content of 178 MUg/kg, with a mean for all studied products of 56 MUg/kg; the maximum contents were found in rice cakes (149 MUg/kg) and brown rice (111 MUg/kg). The estimated daily intake of i-As were 0.16 and 0.18 MUg/kg bw (body weight)/d, in sportsmen and sportswomen, respectively. These values were below the BMDL01 , 0.3 to 8.0 MUg/kg bw/d; thus, it can be concluded that the sportspeople group is not at a significant risk regarding the intake of i-As. However, further studies are needed to evaluate their whole diet and not only rice-based products. Finally, it is important to claim that companies producing rice products include as much information as possible about the rice used in their products, including rice percentage and geographical origin. PMID- 26990092 TI - Variation and association of fibronectin-binding protein genes fnbA and fnbB in Staphylococcus aureus Japanese isolates. AB - Fibronectin-binding proteins A and B (FnBPA and FnBPB) mediate adhesion of Staphylococcus aureus to fibrinogen, elastin and fibronectin. FnBPA and FnBPB are encoded by two closely linked genes, fnbA and fnbB, respectively. With the exception of the N-terminal regions, the amino acid sequences of FnBPA and FnBPB are highly conserved. To investigate the genetics and evolution of fnbA and fnbB, the most variable regions, which code for the 67th amino acids of the A through B regions (A67-B) of fnbA and fnbB, were focused upon. Eighty isolates of S. aureus in Japan were sequenced and 19 and 18 types in fnbA and fnbB, respectively, identified. Although the phylogeny of fnbA and fnbB were found to be quite different, each fnbA type connected with a specific fnbB type, indicating that fnbA and fnbB mutate independently, whereas the combination of both genes after recombination is stable. Hence those fnbA-fnbB combinations were defined as FnBP sequence types (FnSTs). Representative isolates of each FnST were assigned distinct STs by multilocus sequence typing, suggesting correspondence of FnST with genome lineage. Linkage disequilibrium (LD) analysis of the A67-B region revealed that subdomains N2, N3 and FnBR1 form a LD block in fnbA, whereas N2 and N3 form two independent LD blocks in fnbB. N2-N3 three-dimensional structural models indicated that not only the variable amino acid residues, but also well conserved amino acid residues between FnBPA and FnBPB, are located on the surface of the protein. These results highlight a molecular process of the FnBP that has evolved by mingled mutation and recombination with retention of functions. PMID- 26990090 TI - ATP1A3 Mutation in Adult Rapid-Onset Ataxia. AB - A 21-year old male presented with ataxia and dysarthria that had appeared over a period of months. Exome sequencing identified a de novo missense variant in ATP1A3, the gene encoding the alpha3 subunit of Na,K-ATPase. Several lines of evidence suggest that the variant is causative. ATP1A3 mutations can cause rapid onset dystonia-parkinsonism (RDP) with a similar age and speed of onset, as well as severe diseases of infancy. The patient's ATP1A3 p.Gly316Ser mutation was validated in the laboratory by the impaired ability of the expressed protein to support the growth of cultured cells. In a crystal structure of Na,K-ATPase, the mutated amino acid was directly apposed to a different amino acid mutated in RDP. Clinical evaluation showed that the patient had many characteristics of RDP, however he had minimal fixed dystonia, a defining symptom of RDP. Successive magnetic resonance imaging (MRI) revealed progressive cerebellar atrophy, explaining the ataxia. The absence of dystonia in the presence of other RDP symptoms corroborates other evidence that the cerebellum contributes importantly to dystonia pathophysiology. We discuss the possibility that a second de novo variant, in ubiquilin 4 (UBQLN4), a ubiquitin pathway component, contributed to the cerebellar neurodegenerative phenotype and differentiated the disease from other manifestations of ATP1A3 mutations. We also show that a homozygous variant in GPRIN1 (G protein-regulated inducer of neurite outgrowth 1) deletes a motif with multiple copies and is unlikely to be causative. PMID- 26990094 TI - Cutaneous reactions to pirfenidone: a new kid on the block. PMID- 26990093 TI - Comparison of the Physical Activity and Sedentary Behaviour Assessment Questionnaire and the Short-Form International Physical Activity Questionnaire: An Analysis of Health Survey for England Data. AB - BACKGROUND: The Physical Activity and Sedentary Behaviour Assessment Questionnaire (PASBAQ), used within the Health Survey for England (HSE) at 5 yearly intervals, is not included annually due to funding and interview-length constraints. Policy-makers and data-users are keen to consider shorter instruments such as the Short-form International Physical Activity Questionnaire (IPAQ) for the annual survey. Both questionnaires were administered in HSE 2012, enabling comparative assessment in a random sample of 1252 adults. METHODS: Relative agreement using prevalence-adjusted bias-adjusted Kappa (PABAK) statistics was estimated for: sufficient aerobic activity (moderate-to-vigorous physical activity [MVPA] >=150 minutes/week); inactivity (MVPA<30 minutes/week); and excessive sitting (>=540 minutes/weekday). Cross-sectional associations with health outcomes were compared across tertiles of MVPA and tertiles of sitting time using logistic regression with tests for linear trend. RESULTS: Compared with PASBAQ data, IPAQ-assessed estimates of sufficient aerobic activity and inactivity were higher and lower, respectively; estimates of excessive sitting were higher. Demographic patterns in prevalence were similar. Agreement using PABAK statistics was fair-to-moderate for sufficient aerobic activity (0.32 0.49), moderate-to-substantial for inactivity (0.42-0.74), and moderate-to substantial for excessive sitting (0.49-0.75). As with the PASBAQ, IPAQ-assessed MVPA and sitting each showed graded associations with mental well-being (women: P for trend = 0.003 and 0.004, respectively) and obesity (women: P for trend = 0.007 and 0.014, respectively). CONCLUSIONS: Capturing habitual physical activity and sedentary behaviour through brief questionnaires is complex. Differences in prevalence estimates can reflect differences in questionnaire structure and content rather than differences in reported behaviour. Treating all IPAQ-assessed walking as moderate-intensity contributed to the differences in prevalence estimates. PASBAQ data will be used for population surveillance every 4 to 5 years. The current version of the Short-form IPAQ was included in HSE 2013-14 to enable more frequent assessment of physical activity and sedentary behaviour; a modified version with different item-ordering and additional questions on walking pace and effort was included in HSE 2015. PMID- 26990095 TI - Purine salvage in Methanocaldococcus jannaschii: Elucidating the role of a conserved cysteine in adenine deaminase. AB - Adenine deaminases (Ade) and hypoxanthine/guanine phosphoribosyltransferases (Hpt) are widely distributed enzymes involved in purine salvage. Characterization of the previously uncharacterized Ade (MJ1459 gene product) and Hpt (MJ1655 gene product) are discussed here and provide insight into purine salvage in Methanocaldococcus jannaschii. Ade was demonstrated to use either Fe(II) and/or Mn(II) as the catalytic metal. Hpt demonstrated no detectable activity with adenine, but was equally specific for hypoxanthine and guanine with a kcat /KM of 3.2 * 10(7) and 3.0 * 10(7) s(- 1) M(- 1) , respectively. These results demonstrate that hypoxanthine and IMP are the central metabolites in purine salvage in M. jannaschii for AMP and GMP production. A conserved cysteine (C127, M. jannaschii numbering) was examined due to its high conservation in bacterial and archaeal homologues. To assess the role of this highly conserved cysteine in M. jannaschii Ade, site-directed mutagenesis was performed. It was determined that mutation to serine (C127S) completely abolished Ade activity and mutation to alanine (C127A) exhibited 10-fold decrease in kcat over the wild type Ade. To further investigate the role of C127, detailed molecular docking and dynamics studies were performed and revealed adenine was unable to properly orient in the active site in the C127A and C127S Ade model structures due to distinct differences in active site conformation and rotation of D261. Together this work illuminates purine salvage in M. jannaschii and the critical role of a cysteine residue in maintaining active site conformation of Ade. Proteins 2016; 84:828 840. (c) 2016 Wiley Periodicals, Inc. PMID- 26990096 TI - Effectiveness of Barrier Creams against Irritant Contact Dermatitis. AB - INTRODUCTION: Skin tissue is frequently exposed to various irritant substances in the workplace, particularly in wet work, which can lead to the development of occupational contact dermatitis. 'Barrier' creams (BCs) are well known, and their applications are still the subject of many studies and controversies. METHODS: We searched all controlled trials investigating BCs against cutaneous irritants in humans published between 1956 and December 2014 from MEDLINE, PubMed, reference lists and existing reviews. RESULTS: Thirty-nine studies about the effects of BCs against skin irritants in humans were selected. Among these, 27 trials in healthy volunteers were found to show many differences with regard to BCs and irritants used, their quantities, test locations, procedures and assessment methods. Finally, 14 patch test trials assessed by clinical scoring and evaporimetry emerged. Although the findings were generally positive, only few findings could be cross-checked from all the data, and vehicles seem to be as effective as BCs. CONCLUSION: Although this review highlights the poor quality and the lack of standardization of most studies, BCs seem to have protective effects against irritants. Further well-designed, adequately powered randomized controlled trials with clinical and biophysical assessments are required. PMID- 26990097 TI - [Bacterial vaginosis: efficacy of a local treatment with a gel containing a fraction derived from propinibacterium acnes]. AB - BACKGROUND: Bacterial vaginosis (BV) is favored by a decreased activity of vaginal immune system. The fraction derived from Propionibacterium acnes is known to activate the immune system and is used parenterally to treat respiratory and urinary infections. The employ of a fraction derived from Propionibacterium acnes locally, in the context of the vaginal immune system, is made possible by a vaginal gel in which this fraction is associated with hyaluronic acid, well-known for its moisturizing activity, and polycarbophil, capable of miming the function of cervical mucus. The aim of the study was to evaluate whether this preparation is efficacy in the treatment of vulvovaginal symptoms associated to BV. METHODS: After the diagnosis of BV and the evaluation of a Visual Analogic Score >6 for vulvovaginal itch and burning, 33 women participated in this study on a voluntary basis. They were treated with a vaginal gel (Immunovag(r), Depofarma, Italy) for 5 days, with one vulvovaginal application a day. RESULTS: The day following the last application, the subjects reported a significant reduction of vulvovaginal symptoms and a significant reduction of vulvovaginal erythema and leucorrhea. In the vaginal swab performed before the treatment, anaerobic microorganisms were positive in 82% and negative in 18% of cases; when tested the day following the end of treatment, it was positive in 25% and negative in 75% of subjects. Symptom reduction rates did not differ between the groups with positive or negative vaginal swab. The results obtained in the subjects treated with Immunovag(r) were similar to those obtained in a group of women with BV treated with clindamycin cream (one daily vulvovaginal application of 100 mg, for 5 days). CONCLUSIONS: The activation of the vaginal immune system induced by Immunovag(r) can antagonize the symptoms of BV and counteract the growth of vaginal anaerobic microorganisms. PMID- 26990098 TI - Repeated-intermittent use of ulipristal acetate for the management of uterine fibroids: an Italian pharmacoeconomic evaluation. AB - BACKGROUND: The aim of this paper was to evaluate an Italian pharmacoeconomic profile of repeated-intermittent (from 4 to 10 cycles) use of ulipristal acetate 5 mg (UPA 5 mg) in comparison with the use of UPA 5 mg before surgery (2 cycles) for the management of symptomatic uterine fibroids. METHODS: The pharmacoeconomic analysis was performed in two steps: 1) estimating an incremental cost effectiveness ratio (ICER); 2) assuming a nationwide prediction of future expenditure in the Italian scenario. Effectiveness data were derived from the randomized-controlled trial, whilst quality of life and costs data were retrieved from the published literature. RESULTS: In comparison with the use of UPA 5 mg before surgery, the values of ICER per patient were the following: 1) ?20,600 euros (UPA 5 mg 4 cycles); 2) ?26,884 (UPA 5mg 6 cycles); 3) ?30,244 (UPA 5 mg 8 cycles); 4) ?31,906 (UPA 5 mg 10 cycles). In comparison with the use of UPA 5 mg before surgery plus subsequent surgery, the saving per patient for the National Healthcare System (NHS) by adding repeated-intermittent use of UPA 5 mg were the following: 1) ?26 million (UPA 5 mg 4 cycles); 2) ?17.6 million (UPA 5mg 6 cycles); 3) ?8.9 million (UPA 5 mg 8 cycles); 4) ?0.2 million (UPA 5 mg 10 cycles). CONCLUSIONS: The results showed that repeated-intermittent use of UPA 5 mg for the long-term treatment of uterine fibroids has a favourable pharmacoeconomic profile up to 10 repeated cycles and may be a cost-saving treatment option for the NHS. Although the data are encouraging, more data are needed regarding the benefits and risks of long-term treatment with UPA. PMID- 26990099 TI - Selection of patients with high risk endometrial cancer for surgical staging according to the evaluation of pre- and intraoperative risk factors. AB - BACKGROUND: The aim of this paper was to assess the accuracy of frozen sections histological examination and preoperative CA-125 to select patients with high risk endometrial cancer. METHODS: We reviewed women with type I endometrial cancer treated from January 2011 through January 2013 at the same university hospital. Preoperative CA-125 and intraoperative frozen sections were analyzed to select patients at high risk for metastases, according to Mayo Clinic algorithm. All patients underwent hysterectomy with bilateral adnexectomy. High risk patients underwent complete surgical staging. Respectively, we compared the accuracy of CA-125, frozen sections, and an algorithm combining Ca-125 plus frozen sections, with permanent sections histology as positive control. chi2 test, Landis and Koch kappa statistics (k), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were determined for each variable. RESULTS: One hundred seventy-two women were included. CA-125 levels, using 8.3 U/ml as cut-off value, showed 63.4% sensitivity, 51.6% specificity, 84.7% PPV, 25.0% NPV, 61.1% accuracy, and a low kappa statistics (k=0.106, P<0.125). Frozen sections demonstrated 97.3% sensitivity, 100% specificity, 100% PPV, 90.0% NPV, 97.8% accuracy and an optimal kappa statistics (k=0.934, P<0.001). The algorithm combining CA-125 with frozen sections showed 99.1% sensitivity, 48.1% specificity, 88.8% PPV, 92.9% NPV, 89.2% accuracy, and a satisfactory kappa statistics (k=0.578, P<0.001). CONCLUSIONS: We proved the utility of Mayo algorithm even in a different institution. Combining CA-125 plus frozen sections doesn't look like advantageous compared to frozen sections alone. PMID- 26990100 TI - Management of cervical pregnancy: a diagnostic and therapeutic approach. PMID- 26990101 TI - Immediate postpartum evaluation of clinical markers for depression symptoms by means of the Edinburgh Postnatal Depression Scale. PMID- 26990102 TI - Thromboprophilaxis in neurological conditions in pregnancy. A clinical dilemma or a methods dilemma? PMID- 26990104 TI - A bioarchaeological analysis of oral and physiological health on the south coast of New Guinea. AB - OBJECTIVES: The south coast of New Guinea has a complex prehistory known for its exchange systems that linked distinct cultural groups living along the coast, inland, and on offshore islands. Here we compare the palaeohealth of two relatively contemporaneous skeletal samples from the south coast of New Guinea (850-200 BP) that were from two ecologically different sites (one inland and one offshore island) and likely represent distinct cultural groups. We aim to elucidate health patterns that may provide information about the specific lifeways and quality of life of each community. MATERIALS AND METHODS: Oral conditions (caries, calculus, alveolar lesions, and antemortem tooth loss [AMTL]) were analyzed macroscopically to assess possible intra- and inter-population variation in oral and physiological health. The frequency of linear enamel hypoplasia (LEH) was also used as a nonspecific indicator of stress to assess childhood health at each site. RESULTS: The inhabitants from the small offshore island of Motupore, thought to be associated with Austronesian-speaking Motu tribes, displayed different patterns of oral pathological conditions (more carious lesions on the tooth crown and calculus) and LEH (lower frequencies) compared with inland people residing at the site of Nebira. DISCUSSION: It is suggested that the causes for the variation in oral and physiological health were likely multifactorial and potentially associated with variables such as the ecological and geographical settings of the sites, cultural differences, infectious disease, differential fertility and, potentially, diet. This research provides previously unknown information about possible culturally-moderated practices that affected health in the past. Am J Phys Anthropol 160:414-426, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990103 TI - Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search. AB - Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Levy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1) a lognormal distribution of step lengths, 2) motion that is directionally persistent over short time scales, and 3) heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call "hotspots" within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search. PMID- 26990105 TI - Spin-State Energetics of Fe(III) and Ru(III) Aqua Complexes: Accurate ab Initio Calculations and Evidence for Huge Solvation Effects. AB - Aqua complexes of transition metals are useful models for understanding the electronic structure of metal-oxide species relevant in photocatalytic water splitting. Moreover, spin-forbidden d-d transitions of aqua complexes provide valuable experimental data of spin-state energetics, which can be used for benchmarking of computational methods. Here, low-energy spin states of Fe(III) and Ru(III) aqua complexes are studied with an array of DFT and high-level wave function methods (CASPT2, RASPT2, NEVPT2, CCSD(T)-F12, and other coupled cluster methods up to full CCSDT). The results from single-reference and multireference methods are cross-checked, and the amount of multireference character for both considered spin states of [Fe(H2O)6](3+) is carefully analyzed. In addition to small [M(H2O)6](3+) clusters (M = Fe, Ru), we also employ larger models [M(H2O)6.(H2O)12](3+), with explicit water molecules in the second coordination sphere, to describe the situation in aqueous solution. By comparing the results for both types of models, our calculations evidence large and systematic solvation effects on the spin-state energetics. It is found that, due to the interaction with hydrogen-bonded water molecules in the second coordination sphere, the first coordination sphere undergoes a noticeable contraction and deformation. In consequence, the presence of solvation shell affects the relative energies of spin states by as much as 3-4 * 10(3) cm(-1) (~10 kcal/mol). Once this solvation effect is accounted for, the spin-state energetics from CCSD(T) and NEVPT2 calculations turn out to be in an excellent agreement with the experimental estimates, which was not the case for isolated [M(H2O)6](3+) species is gas phase. We thus postulate that significant discrepancies between theory and experimental data for [Fe(H2O)6](3+) that were previously reported in the literature may be plausibly resolved and attributed to the neglect of explicit solvation effects and also, to some extent, to incompleteness of the active space and/or basis set used in the previous theoretical studies. The findings of this work contradict an anecdotal conjecture that energies of ligand-field (d-d) transitions are almost unaffected by solvation. On the contrary, it is highlighted that medium effects may contribute very significantly to spin-state energetics of transition metal complexes. PMID- 26990106 TI - Rbm24 Regulates Alternative Splicing Switch in Embryonic Stem Cell Cardiac Lineage Differentiation. AB - The transition of embryonic stem cell (ESC) pluripotency to differentiation is accompanied by an expansion of mRNA and proteomic diversity. Post-transcriptional regulation of ESCs is critically governed by cell type-specific splicing. However, little is known about the splicing factors and the molecular mechanisms directing ESC early lineage differentiation. Our study identifies RNA binding motif protein 24 (Rbm24) as a key splicing regulator that plays an essential role in controlling post-transcriptional networks during ESC transition into cardiac differentiation. Using an inducible mouse ESC line in which gene expression could be temporally regulated, we demonstrated that forced expression of Rbm24 in ESCs dramatically induced a switch to cardiac specification. Genome-wide RNA sequencing analysis identified more than 200 Rbm24-regulated alternative splicing events (AS) which occurred in genes essential for the ESC pluripotency or differentiation. Remarkably, AS genes regulated by Rbm24 composed of transcriptional factors, cytoskeleton proteins, and ATPase gene family members which are critical components required for cardiac development and functionality. Furthermore, we show that Rbm24 regulates ESC differentiation by promoting alternative splicing of pluripotency genes. Among the Rbm24-regulated events, Tpm1, an actin filament family gene, was identified to possess ESC/tissue specific isoforms. We demonstrated that these isoforms were functionally distinct and that their exon AS switch was essential for ESC differentiation. Our results suggest that ESC's switching into the differentiation state can be initiated by a tissue-specific splicing regulator, Rbm24. This finding offers a global view on how an RNA binding protein influences ESC lineage differentiation by a splicing mediated regulatory mechanism. Stem Cells 2016;34:1776-1789. PMID- 26990107 TI - Movement and survival of Busseola fusca (Lepidoptera: Noctuidae) larvae within maize plantings with different ratios of non-Bt and Bt seed. AB - BACKGROUND: Products of plant biotechnology, for example genetically modified Bt maize, provide useful tools for pest management. The benefits provided by insect resistant plants are, however, threatened by the evolution of resistance by target pest species. The high-dose/refuge insect resistance management strategy (IRM) as well as seed mixtures are globally used as IRM strategies. Busseola fusca (Lepidoptera: Noctuidae), the target stem borer of Bt maize in Africa, evolved resistance to Bt maize expressing Cry1Ab protein in South Africa. Owing to high larval mobility and subsequent sublethal exposure of larvae moving between non-Bt and Bt plants, more rapid resistance evolution has been proposed as a possibility with deployment of seed mixture strategies. RESULTS: Laboratory and field studies were conducted to study B. fusca larval mobility. In the laboratory, different scenarios of B. fusca larval movement between single-gene (Cry1Ab) and stacked-trait (Cry1A.105 and Cry2Ab2) Bt maize were studied. Data on larval survival and mass over time indicated that Cry proteins do not kill larvae above certain developmental stages. A 2 year field study with the single gene and the stacked event was conducted using seed mixtures containing 5, 10, 15 and 20% non-Bt seed as well as a control treatment (non-Bt seed only). CONCLUSION: Larval movement continued for 5 weeks and resulted in a significant incidence of Bt and non-Bt damaged plants, indicating that the movement behaviour of B. fusca is of such a nature that seed mixtures as an IRM strategy may not be effective to delay resistance evolution. (c) 2016 Society of Chemical Industry. PMID- 26990108 TI - Prairie vole pups show potentiated isolation-induced vocalizations following isolation from their mother, but not their father. AB - Vocalizations can be markers of emotional social communication. Maternal potentiation was originally described as an increased rate of vocalization by isolated rat pups following an interaction with their mothers, but not with other social companions. Here we asked if potentiation in prairie voles, a species with pair-bonding and bi-parental rearing, is parent-specific. We found that isolated, 8-11-day-old voles exhibited potentiation following reunions with the dam, but not the sire. These responses were present whether parents were anesthetized or active during the reunion. There were no significant correlations between parental behaviors during reunions and pup vocalization rates during re isolation. The absence of potentiation to the sire contrasts to findings in bi parentally reared rat pups, which do potentiate vocalizations to the sire. We interpret these results to be consistent with the idea that potentiation reflects disruption of mother-infant coregulation and is dependent upon the unique biology of mothering. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:687-699, 2016. PMID- 26990109 TI - Real-world medical costs of antiviral therapy among patients with chronic HCV infection and advanced hepatic fibrosis. AB - BACKGROUND AND AIMS: Very potent direct acting antivirals for the treatment of chronic hepatitis C virus infection were recently introduced into daily clinical practice. Currently, treatment uptake is hampered by their high costs, eliciting prioritization of treatment. We aimed to evaluate the direct medical costs during interferon (IFN)-based antiviral treatment and the costs per sustained virological response (SVR) among patients with advanced hepatic fibrosis. METHODS: This retrospective cohort study included all consecutive patients with chronic hepatitis C virus infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) treated with IFN-based regimens in five hepatology units of tertiary care centers in Europe and Canada. Direct medical costs, expressed in 2013 Euros, during therapy were assessed. The components of care were quantified by three distinct categories: treatment, safety/ monitoring, and complications. Cost per SVR was calculated by dividing the mean cost by the SVR rate. RESULTS: In total, 672 interferon-based treatments administered to 455 patients were included. Total medical costs per patient were averaged to ?14 559 (95% confidence interval [CI], ?13 323-?15 836). The mean cost per SVR was ?38 514 (95% CI, ?35 244-?41 892). The costs per SVR were ?26 105 (95% CI, ?23 068-?29 296) for patients with a normal platelet count and ?50 907 (95% CI, ?44 151-?59 612) for patients with thrombocytopenia, with the costs per SVR of ?74 961 (95% CI, ?55 463-?103 541) among those patients with a platelet count below 100 * 109 /L. CONCLUSIONS: Because of the lower SVR rates, the cost per SVR of IFN-based treatment increased when patients with more advanced liver disease were treated. Additional costs of IFN-free therapy could be limited among these patients. PMID- 26990110 TI - Savoring moderates the association between cancer-specific physical symptoms and depressive symptoms. AB - BACKGROUND: This study investigated the associations of savoring with cancer specific physical symptoms, psychological distress, and psychological well-being and the moderating effect of savoring in the associations between physical symptoms and psychological outcomes among cancer patients. METHODS: A total of 263 Chinese adults recently diagnosed with cancer (mean time since diagnosis = 43.72 days, SD = 38.20) were recruited and administered a questionnaire assessing cancer-specific physical symptoms, perceived capability of savoring the moment, psychological distress, and psychological well-being within six months following diagnosis. RESULTS: Structural equation modeling revealed significant associations of savoring with physical symptoms and psychological distress and well-being (beta = -0.41-0.54, p < 0.0001). Savoring significantly moderated the association between physical symptoms and depressive symptoms. Simple slope tests revealed that the association was not significant at higher levels of savoring (estimate = 0.15, z = 0.49, p = 0.62) whereas it was stronger at lower (estimate = 1.11, z = 4.81, p < 0.001) and medium (estimate = 0.63, z = 3.04, p < 0.01) levels of savoring. The effects of demographic and medical covariates were controlled for in all models. CONCLUSIONS: The findings suggest that savoring is positively associated with physical and psychological functioning among people with cancer. The link between physical symptoms and depressive symptoms could be exacerbated at lower levels of savoring. Fostering savoring beliefs and practices could be a significant psychological component of symptom management among cancer patients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990111 TI - MALDI imaging for the localization of saponins in root tissues and rapid differentiation of three Panax herbs. AB - The roots of Panax genus with ginseng saponins as bioactive ingredients have been widely used as herbal medicines and food additives. Panax ginseng, Panax quinquefolius, and Panax notoginseng are three major commercial species in Panax genus, with similar morphological appearance but different pharmacological functions. Various methods have been developed and applied for the differentiation of these species. In this work, MALDI-TOF-MS imaging (MSI) was employed for the localization of saponins in root tissues and for the rapid differentiation of the three Panax species for the first time. After a simple sample preparation, MALDI-TOF-MSI analysis of root tissue allowed the detection of 51 saponins. Localization of saponins in the tissue was mapped in ion images, which were obviously related to botanical structure. The localization modes varied with Panax species, providing valuable information for the discrimination of ginseng species. Principal component analysis (PCA) of data collected from areas with abundant saponins based on ion images was applied for the differentiation. Nine characteristic saponin peaks were identified from the PCA analysis. The MALDI-TOF-MSI together with area-specific data analysis provided high potential for the rapid differentiation of Panax herbs. PMID- 26990112 TI - Enigmatic human tails: A review of their history, embryology, classification, and clinical manifestations. AB - The presence of a human tail is a rare and intriguing phenomenon. While cases have been reported in the literature, confusion remains with respect to the proper classification, definition, and treatment methods. We review the literature concerning this anatomical derailment. We also consider the importance of excluding underlying congenital anomalies in these patients to prevent neurological deficits and other abnormal manifestations. PMID- 26990113 TI - Correlates of children's compliance with moderate-to-vigorous physical activity recommendations: a multilevel analysis. AB - This study aimed to investigate the association between individual and school characteristics associated with the number of school days children comply with moderate-to-vigorous physical activity (MVPA) recommendations. Sample comprises 612 Portuguese children, aged 9-11 years, from 23 schools. Time spent in MVPA was measured by accelerometry, while individual-level correlates were obtained by anthropometry and questionnaires. School-level variables were collected by questionnaire, and accelerometer wear time and season were also considered. Maximum likelihood estimates of model parameters were obtained via a multilevel analysis with children as level-1, and school as level-2. Children who spent more time in sedentary activities and girls were less likely to comply with MVPA/daily. More mature children and those who use active transportation to school were more likely to attain the PA recommendation. Furthermore, greater accelerometer wear time and spring season increased the chance to achieve the recommended MVPA. In terms of school-level correlates, a greater number of available facilities was negatively associated with children MVPA compliance. Given the set of variables, our results showed that individual characteristics seem to be more relevant for children's compliance rates with PA/day than school context variables, which should be taken into account in the implementation of school policies and practices. PMID- 26990115 TI - Quantitative Characterization of the Interaction Space of the Mammalian Carbonic Anhydrase Isoforms I, II, VII, IX, XII, and XIV and their Inhibitors, Using the Proteochemometric Approach. AB - The critical role of carbonic anhydrases in different physiological processes has put this protein family at the center of attention, challenging major diseases like glaucoma, neurological disorders such as epilepsy and Alzheimer's disease, obesity, and cancers. Many QSAR/QSPR (quantitative structure-activity/property relationship) researches have been carried out to design potent carbonic anhydrase inhibitors (CAIs); however, using inhibitors with no selectivity for different isoforms can lead to major side-effects. Given that QSAR/QSPR methods are not capable of covering multiple targets in a unified model, we have applied the proteochemometric approach to model the interaction space that governs selective inhibition of different CA isoforms by some mono-/dihydroxybenzoic acid esters. Internal and external validation methods showed that all models were reliable in terms of both validity and predictivity, whereas Y-scrambling assessed the robustness of the models. To prove the applicability of our models, we showed how structural changes of a ligand can affect the selectivity. Our models provided interesting information that can be useful for designing inhibitors with selective behavior toward isoforms of carbonic anhydrases, aiding in their selective inhibition. PMID- 26990114 TI - Physician and Practice-Level Drivers and Disparities around Meaningful Use Progress. AB - OBJECTIVE: To identify physician and practice characteristics that are markers of success for meaningful use of electronic health records (EHRs). DATA SOURCES: American Medical Association survey, Centers for Medicare & Medicaid Services' (CMS) EHR Incentive, Pioneer Accountable Care Organization, and PECOS Programs, the Office of the National Coordinator for Health IT's Regional Extension Center Program, and National Committee for Quality Assurance Patient-centered Medical Home certification program. STUDY DESIGN: Retrospective analysis of 865,370 physicians' participation in CMS's EHR Incentive Program and progress to stage 1 Meaningful Use between 2011 and 2013. Physician specialty, age, practice size, geographic markers, delivery reform participation, and technical assistance receipt were predictive elements. PRINCIPAL FINDINGS: Medicaid physicians were progressing more slowly to Meaningful Use than Medicare physicians: by 2013, 8 in 10 physicians registered with Medicare had achieved meaningful use, compared to one-third of Medicaid-registered physicians. The strongest predictors of meaningful use were technical assistance (79 percent more likely) and delivery reform participation (34 percent more likely). CONCLUSIONS: Continued outreach and technical assistance that demonstrates strong interactions between meaningful use of health IT and delivery reform may facilitate further adoption of both initiatives. PMID- 26990116 TI - Erythrocyte osmotic fragility and select hematologic variables in postparturient mares and their foals. AB - BACKGROUND: Knowledge of hematologic function in postparturient mares and foals is crucial for the monitoring of their health status and for the prompt diagnosis of pathologic conditions. OBJECTIVES: The aim of this study was to evaluate erythrocyte osmotic fragility (EOF) and select hematologic variables in mares and their foals during the first month after foaling. METHODS: Blood samples were collected from each animal every 3 days from day 1 until day 30 after foaling, and tested for RBC count, HGB, HCT, MCV, and EOF. Two-way repeated measures analysis of variance (ANOVA) and Bonferroni post hoc comparison test were applied to determine the effects of time and age (mares vs foals). Pearson correlation coefficients were computed for EOF and time or MCV values. RESULTS: There was a significant effect of time in RBC, HGB, HCT, and EOF (P < .001). Statistically significant differences were observed between mares and foals for RBC, MCV, and EOF (P < .05) throughout the experimental period. Significant correlations between EOF and both time and MCV (P < .05) were found in mares as well as in foals. CONCLUSION: These results contribute to the understanding of perinatal changes in hematologic variables in mares and foals. In addition, the data support the relevance of specific reference intervals for postparturient mares and foals. The findings also provide useful information that could help clinicians to better interpret clinical data and diagnose equine disease. PMID- 26990117 TI - Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor. AB - Drug-drug interaction (DDI) studies involving warfarin are typically conducted with subtherapeutic doses of warfarin to ensure the safety of volunteers. However, this approach may potentially have a systemic bias of underestimating pharmacodynamic (PD) DDI effect on warfarin at therapeutic levels of anticoagulation. We demonstrate here the utility of model-based DDI prediction for a clinically relevant warfarin regimen, using the example of epacadostat (INCB024360), the first-in-class indoleamine 2,3-dioxygenase 1 inhibitor in clinical development as a novel orally active immuno-oncological therapy. Observed data from a dedicated clinical DDI study using subtherapeutic warfarin suggested warfarin pharmacokinetics (PK), but not PD (anticoagulation), was significantly affected by concomitant epacadostat. However, subsequent PK/PD modeling and simulations indicated a clinically important DDI effect on warfarin PD at a higher baseline of the international normalization ratio (INR) and enabled recommendation of warfarin dose adjustment that is dependent on epacadostat dosing regimen and target INR. PMID- 26990118 TI - Causal network analysis of head and neck keloid tissue identifies potential master regulators. AB - OBJECTIVES/HYPOTHESIS: To generate novel insights and hypotheses in keloid development from potential master regulators. STUDY DESIGN: Prospective cohort. METHODS: Six fresh keloid and six normal skin samples from 12 anonymous donors were used in a prospective cohort study. Genome-wide profiling was done previously on the cohort using the Infinium HumanMethylation450 BeadChip (Illumina, San Diego, CA). The 190 statistically significant CpG islands between keloid and normal tissue mapped to 152 genes (P < .05). The top 10 statistically significant genes (VAMP5, ACTR3C, GALNT3, KCNAB2, LRRC61, SCML4, SYNGR1, TNS1, PLEKHG5, PPP1R13-alpha, false discovery rate <.015) were uploaded into the Ingenuity Pathway Analysis software's Causal Network Analysis (QIAGEN, Redwood City, CA). To reflect expected gene expression direction in the context of methylation changes, the inverse of the methylation ratio from keloid versus normal tissue was used for the analysis. Causal Network Analysis identified disease-specific master regulator molecules based on downstream differentially expressed keloid-specific genes and expected directionality of expression (hypermethylated vs. hypomethylated). RESULTS: Causal Network Analysis software identified four hierarchical networks that included four master regulators (pyroxamide, tributyrin, PRKG2, and PENK) and 19 intermediate regulators. CONCLUSIONS: Causal Network Analysis of differentiated methylated gene data of keloid versus normal skin demonstrated four causal networks with four master regulators. These hierarchical networks suggest potential driver roles for their downstream keloid gene targets in the pathogenesis of the keloid phenotype, likely triggered due to perturbation/injury to normal tissue. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E319-E324, 2016. PMID- 26990119 TI - RISK OF NEW ONSET TYPE II DM IN MDD PATIENTS RECEIVING SECOND-GENERATION ANTIPSYCHOTICS TREATMENT: A NATIONWIDE COHORT STUDY. AB - BACKGROUND: Second-generation antipsychotics (SGA) augmentation treatment has showed better efficacy in patients with major depressive disorder (MDD). However, the association between SGA and diabetes mellitus (DM) in MDD patients deserves further investigation. The study aimed to examine the risk of new onset type II DM in MDD patients receiving SGA treatment. METHODS: From the Psychiatric Inpatient Medical Claim Dataset, MDD patients treated with SGA continuously for more than 8 weeks were analyzed in a 1:1 propensity score matched pair sample to 1,049 patients that had never been treated with SGA. Patients were followed up to 5 years based on ICD-9 CM codes indicating incident type II DM. Cumulative incidences of type II DM were calculated and the Cox proportional hazards model with competing risk was applied to determine the risk factors for type II DM onset. RESULTS: Cumulative incidences of new-onset type II DM between the two groups were similar. Use of SGA showed no significant increase in risk for new onset type II DM (hazard ratio [HR] = 0.898; 95% confidence interval [CI], 0.605 1.334; P-value = 0.596). Increased risk for type II DM was shown to be associated with aging (per year) (HR = 1.039; 95% CI, 1.026-1.053; P-value < 0.001) and history of hyperlipidemia (HR = 2.323; 95% CI, 1.469-3.675; P-value < 0.001). CONCLUSIONS: This study indicated that there is no significant difference in the risk of developing type II DM between MDD patients with and without SGA exposure. More studies focused on the benefit-risk assessment of SGA treatment in patients with MDD are warranted. PMID- 26990120 TI - Enantioselective Synthesis of Isoquinolines: Merging Chiral-Phosphine and Gold Catalysis. AB - The highly enantioselective synthesis of dihydroisoquinoline derivatives from aromatic sulfonated imines tethered with an alkyne moiety, through a one-pot asymmetric relay catalysis of chiral-phosphine and gold catalysts, is reported. Enantiomerically enriched dihydroisoquinoline derivatives were afforded in good yields and good-to-excellent ee values under mild conditions, based on the asymmetric aza-Morita-Baylis-Hillman reaction. Dihydroisoquinoline derivatives containing two chiral centers were also synthesized through further transformations. PMID- 26990121 TI - Cationic Five-Coordinate Bis(guanidinato)silicon(IV) Complexes with SiN4 El Skeletons (El=S, Se): "Heterolytic Activation" of S-S and Se-Se Bonds. AB - The donor-stabilized silylene [iPrNC(NiPr2 )NiPr]2 Si (2) reacts with PhEl-ElPh (El=S, Se) to form the respective cationic five-coordinate bis(guanidinato)silicon(IV) complexes {[iPrNC(NiPr2 )NiPr]2 SiSPh}(+) PhS(-) (4) and {[iPrNC (NiPr2 )NiPr]2 SiSePh}(+) PhSe(-) (5). Compounds 4 and 5 were characterized by crystal structure analyses and NMR spectroscopic studies in the solid state. PMID- 26990122 TI - MALDI imaging mass spectrometry of Pacific White Shrimp L. vannamei and identification of abdominal muscle proteins. AB - MALDI imaging mass spectrometry (IMS) has been applied to whole animal tissue sections of Pacific White Shrimp, Litopenaeus vannamei, in an effort to identify and spatially localize proteins in specific organ systems. Frozen shrimp were sectioned along the ventral-dorsal axis and methods were optimized for matrix application. In addition, tissue microextraction and homogenization was conducted followed by top-down LC-MS/MS analysis of intact proteins and searches of shrimp EST databases to identify imaged proteins. IMS images revealed organ system specific protein signals that highlighted the hepatopancreas, heart, nervous system, musculature, and cuticle. Top-down proteomics identification of abdominal muscle proteins revealed the sequence of the most abundant muscle protein that has no sequence homology to known proteins. Additional identifications of abdominal muscle proteins included titin, troponin-I, ubiquitin, as well as intact and multiple truncated forms of flightin; a protein known to function in high frequency contraction of insect wing muscles. The combined use of imaging mass spectrometry and top-down proteomics allowed for identification of novel proteins from the sparsely populated shrimp protein databases. PMID- 26990123 TI - The Irrelevance Narrative: Queer (In)Visibility in Medical Education and Practice. AB - How might heteronormativity be reproduced and become internalized through biomedical practices? Based on in-depth, person-centered interviews, this article explores the ways heteronormativity works into medical education through the hidden curriculum. As experienced by my informants, case studies often reinforce unconscious heteronormative orientations and heterosexist/homophobic stereotypes about queer patients among straight and queer medical students alike. I introduce the concept of the irrelevance narrative to make sense of how queer medical students take up a heteronormative medical gaze. Despite recognizing that being queer affects how they interact with patients, my informants describe being queer as irrelevant to their delivery of care. I conclude with a discussion of how these preliminary findings can inform research on knowledge production in biomedical education and practice with an eye toward the tensions between personal and professional identity among biomedical practitioners. PMID- 26990126 TI - Legal Assessments of Child Victims of Human Trafficking for Sexual Purposes. AB - The present study investigated how Swedish district court judges assessed child victims' credibility and the reliability of their testimony in cases of alleged human trafficking for sexual purposes. Court files from 12 different cases, involving 16 alleged child victims (aged 13-17 years old), all of them girls, were qualitatively analyzed with particular attention paid to how the judges described credibility and reliability. Results indicated that, although the judges' assessments to a large extent were based on the Swedish Supreme Court's criteria for credibility and reliability, they were applied somewhat arbitrarily and subjectively. They were also applied as if obvious and grounded on shared experiences, although their meaning was never explored. The way that credibility was assessed may also reinforce gender and victim stereotypes. Moreover, there seems to exist a confusion surrounding the credibility and reliability concepts, as they were sometimes used interchangeably despite the intention that they are two different assessments. Overall, an apparent need exists to increase judges' awareness that their subjective impressions should decrease when legitimizing judicial decisions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990125 TI - Polypharmacy of medications and fall-related fractures in older people in Japan: a comparison between driving-prohibited and driving-cautioned medications. AB - WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is a risk factor for fall-related fractures. However, it is unclear whether polypharmacy itself is a direct risk factor. The aim of this study was to assess the association between the risk of fall-related fractures and polypharmacy of driving-prohibited and driving cautioned medications in older outpatients. METHODS: We conducted a cross sectional study of outpatients aged >=65 years receiving any medication, using two sampling data sets from the October 2011 and October 2012 national insurance claims in Japan. Using logistic regression models, we analysed the association between the numbers of driving-prohibited or driving-cautioned medications administered or dispensed to patients and the occurrence of fall-related fractures. RESULTS AND DISCUSSION: In both analysis populations (n = 303 311 and n = 326 219), the adjusted odds ratio of driving-prohibited medications for the occurrence of fall-related fractures significantly increased as the number of these medications per patient increased (95% confidence interval: 0, 1-2, 3-4, 5 6, 7-8 and >=9 medications; reference, 0.95-1.24, 1.18-1.79, 1.47-2.96, 1.26-5.21 and 1.50-15.2 in October 2011 and reference, 1.11-1.42, 1.39-2.03, 1.33-2.72, 1.53-5.49 and 1.30-13.0 in October 2012). The association was maintained even for sensitivity analyses restricted to medications administered orally or orally and by injection. However, a similar association was not observed for driving cautioned medications. WHAT IS NEW AND CONCLUSION: Medication class is a more important risk factor for fall-related fractures rather than polypharmacy alone with no regard to medication class. PMID- 26990128 TI - Dual Inhibition of Ca(+2) Influx and Phosphodiesterase Enzyme Provides Scientific Base for the Medicinal Use of Chrozophora prostrata Dalz. in Respiratory Disorders. AB - The crude ethanolic extract of Chrozophora prostrata (Cp.Cr) was tested using in vivo and ex vivo assays for its possible bronchodilatory effects in order to validate its medicinal use in respiratory disorders, like asthma and cough. Cp.Cr exhibited dose-dependent inhibition of carbachol (CCh)-induced bronchospasm in anesthetized rats, similar to aminophylline. When tested on guinea-pig tracheal preparations, Cp.Cr caused relaxation of both CCh (1 MUM) and high K(+) (80 mM) induced contractions with comparable potencies, similar to papaverine, a dual inhibitor of phosphodiesterse (PDE) and Ca(+2) influx. Pre-treatment of the tracheal tissues with Cp.Cr resulted in potentiation of the inhibitory effect of isoprenaline on CCh-induced contractions, like that caused by papaverine indicative of PDE inhibitory activity, which was confirmed when Cp.Cr concentration dependently (1 and 3 mg/mL) increased intracellular cAMP levels of the tracheal preparations, like papaverine. Cp.Cr shifted concentrationresponse curves of Ca(+2) constructed in guinea-pig tracheal preparation towards right with suppression of the maximum response, similar to both verapamil and papaverine. These data indicate bronchodilator activity of Chrozophora prostrata mediated possibly through dual inhibition of PDE and Ca(+2) influx, thus, showing therapeutic potential in asthma with effect enhancing and side-effect neutralizing potential Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990124 TI - Bulked sample analysis in genetics, genomics and crop improvement. AB - Biological assay has been based on analysis of all individuals collected from sample populations. Bulked sample analysis (BSA), which works with selected and pooled individuals, has been extensively used in gene mapping through bulked segregant analysis with biparental populations, mapping by sequencing with major gene mutants and pooled genomewide association study using extreme variants. Compared to conventional entire population analysis, BSA significantly reduces the scale and cost by simplifying the procedure. The bulks can be built by selection of extremes or representative samples from any populations and all types of segregants and variants that represent wide ranges of phenotypic variation for the target trait. Methods and procedures for sampling, bulking and multiplexing are described. The samples can be analysed using individual markers, microarrays and high-throughput sequencing at all levels of DNA, RNA and protein. The power of BSA is affected by population size, selection of extreme individuals, sequencing strategies, genetic architecture of the trait and marker density. BSA will facilitate plant breeding through development of diagnostic and constitutive markers, agronomic genomics, marker-assisted selection and selective phenotyping. Applications of BSA in genetics, genomics and crop improvement are discussed with their future perspectives. PMID- 26990127 TI - Sphingosine 1-phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons. AB - Sphingosine 1-phosphate (S1P) is an important regulator of vascular integrity and immune cell migration, carried in plasma by high-density lipoprotein (HDL) associated apolipoprotein M (apoM) and by albumin. In sepsis, the protein and lipid composition of HDL changes dramatically. The aim of this study was to evaluate changes in S1P and its carrier protein apoM during sepsis. For this purpose, plasma samples from both human sepsis patients and from an experimental Escherichia coli sepsis model in baboons were used. In the human sepsis cohort, previously studied for apoM, plasma demonstrated disease-severity correlated decreased S1P levels, the profile mimicking that of plasma apoM. In the baboons, a similar disease-severity dependent decrease in plasma levels of S1P and apoM was observed. In the lethal E. coli baboon sepsis, S1P decreased already within 6 8 hrs, whereas the apoM decrease was seen later at 12-24 hrs. Gel filtration chromatography of plasma from severe human or baboon sepsis on Superose 6 demonstrated an almost complete loss of S1P and apoM in the HDL fractions. S1P plasma concentrations correlated with the platelet count but not with erythrocytes or white blood cells. The liver mRNA levels of apoM and apoA1 decreased strongly upon sepsis induction and after 12 hr both were almost completely lost. In conclusion, during septic challenge, the plasma levels of S1P drop to very low levels. Moreover, the liver synthesis of apoM decreases severely and the plasma levels of apoM are reduced. Possibly, the decrease in S1P contributes to the decreased endothelial barrier function observed in sepsis. PMID- 26990129 TI - Quantitative analysis of oyster larval proteome provides new insights into the effects of multiple climate change stressors. AB - The metamorphosis of planktonic larvae of the Pacific oyster (Crassostrea gigas) underpins their complex life-history strategy by switching on the molecular machinery required for sessile life and building calcite shells. Metamorphosis becomes a survival bottleneck, which will be pressured by different anthropogenically induced climate change-related variables. Therefore, it is important to understand how metamorphosing larvae interact with emerging climate change stressors. To predict how larvae might be affected in a future ocean, we examined changes in the proteome of metamorphosing larvae under multiple stressors: decreased pH (pH 7.4), increased temperature (30 degrees C), and reduced salinity (15 psu). Quantitative protein expression profiling using iTRAQ LC-MS/MS identified more than 1300 proteins. Decreased pH had a negative effect on metamorphosis by down-regulating several proteins involved in energy production, metabolism, and protein synthesis. However, warming switched on these down-regulated pathways at pH 7.4. Under multiple stressors, cell signaling, energy production, growth, and developmental pathways were up-regulated, although metamorphosis was still reduced. Despite the lack of lethal effects, significant physiological responses to both individual and interacting climate change related stressors were observed at proteome level. The metamorphosing larvae of the C. gigas population in the Yellow Sea appear to have adequate phenotypic plasticity at the proteome level to survive in future coastal oceans, but with developmental and physiological costs. PMID- 26990130 TI - Treg subsets in inflammatory bowel disease and colorectal carcinoma: Characteristics, role, and therapeutic targets. AB - T regulatory cells (Tregs) play an important role in the regulation of autoimmunity, autoinflammation, allergic diseases, infection, and the tumor environment. Different subsets are characterized that use a number of regulatory mechanisms. Tregs can influence the progression of inflammatory bowel disease and the development of colorectal cancer. Knowledge of Tregs and their regulatory mechanisms can provide new targets for therapeutic intervention. PMID- 26990131 TI - The use of rivaroxaban for the treatment of thrombotic complications in four dogs. AB - OBJECTIVE: To describe the clinical use of rivaroxaban in the treatment of 4 dogs with vascular thrombosis, 2 with pulmonary thromboembolism and 2 with systemic thrombosis. CASE SERIES SUMMARY: This report describes the use of a direct factor Xa anticoagulant newly approved in human patients for the treatment or prevention of arterial or venous thrombosis. The use of this medication in a clinical setting for canine patients with thromboembolism has not been described before. Two patients were treated with rivaroxaban for pulmonary thromboembolism. Decreases in thrombus size were seen in both patients, but one patient suffered acute respiratory distress and was euthanized while the other continued to do well at the time of this writing. The other 2 patients were treated for systemic thrombosis. Decreases in thrombus size were also noted. One patient later suffered hematochezia of unknown cause, and the other continued to do well at the time of this writing. NEW OR UNIQUE INFORMATION PROVIDED: This is the first published report of the use of a new oral direct factor Xa anticoagulant in dogs in a clinical setting for the treatment of both pulmonary and systemic thrombosis. In this case series, we share our limited experience in the use of this new medication, our strategy in determining appropriate dosages, and our monitoring protocol. PMID- 26990132 TI - Fundic gland differentiation of oncocytic/pancreatobiliary subtypes of pancreatic intraductal papillary mucinous neoplasm. AB - AIMS: Intraductal papillary mucinous neoplasms (IPMNs) differentiate in several histological directions, which are related to their clinical behaviour. Differentiation of IPMNs to the gastric foveolar epithelium/pyloric gland (PG) is well known. However, no study has been conducted regarding fundic gland (FG) differentiation. The aim of this study was to determine the frequency of FG differentiation and its relationship with the clinicopathological features of IPMNs, by studying 48 surgically resected IPMN cases consisting of 17 gastric IPMNs, 15 intestinal IPMNs, 10 pancreatobiliary IPMNs, and six oncocytic IPMNs. METHODS AND RESULTS: Clinicopathological data, including histological tumour grade, immunohistochemical data for mucins (MUCs), pepsinogen I, pepsinogen II, and H,K-ATPase, and GNAS/KRAS status, were analysed. Pepsinogen I and H,K-ATPase were used to assess FG differentiation, and pepsinogen II and MUC6 were used to identify the equivalent cell type of the normal FG. Reverse transcription polymerase chain reaction (RT-PCR) for PGA5/PGC (pepsinogen I and pepsinogen II mRNA, respectively) and quantitative real-time RT-PCR (qRT-PCR) for PGA5 were performed to confirm the immunohistochemistry results. Pepsinogen I expression was detected in 12.5% (6/48) of total IPMNs, of which 66.7% (4/6) of oncocytic IPMNs and 20.0% (2/10) of pancreatobiliary IPMNs were pepsinogen I-positive. No H,K-ATPase-positive cases were detected. Three oncocytic IPMNs with pepsinogen I expression showed similar histology to normal FG. RT-PCR and qRT-PCR confirmed the immunohistochemical results. All IPMNs with FG differentiation were of the oncocytic or pancreatobiliary subtype, were of histologically high grade, and were without GNAS mutation. CONCLUSIONS: The differentiation of IPMNs to gastric FG is related to oncocytic and pancreatobiliary subtypes, and to high grade. This is the first report to describe differentiation of IPMNs to the FG, and to reveal its relationship with the clinicopathological features of IPMNs. PMID- 26990134 TI - Studies on Cycloheptathiophene-3-carboxamide Derivatives as Allosteric HIV-1 Ribonuclease H Inhibitors. AB - Despite the significant progress achieved with combination antiretroviral therapy in the fight against human immunodeficiency virus (HIV) infection, the difficulty to eradicate the virus together with the rapid emergence of multidrug-resistant strains clearly underline a pressing need for innovative agents, possibly endowed with novel mechanisms of action. In this context, owing to its essential role in HIV genome replication, the reverse transcriptase associated ribonuclease H (RNase H) has proven to be an appealing target. To identify new RNase H inhibitors, an in-house cycloheptathiophene-3-carboxamide library was screened; this led to compounds endowed with inhibitory activity, the structural optimization of which led to the catechol derivative 2-(3,4-dihydroxybenzamido)-N (pyridin-2-yl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (compound 33) with an IC50 value on the RNase H activity in the nanomolar range. Mechanistic studies suggested selective inhibition of the RNase H through binding to an innovative allosteric site, which could be further exploited to enrich this class of inhibitors. PMID- 26990135 TI - Evaluation of an online three-dimensional interactive resource for undergraduate neuroanatomy education. AB - Neuroanatomy is one of the most challenging subjects in anatomy, and novice students often experience difficulty grasping the complex three-dimensional (3D) spatial relationships. This study evaluated a 3D neuroanatomy e-learning module, as well as the relationship between spatial abilities and students' knowledge in neuroanatomy. The study's cross-over design divided the participants into two groups, each starting with tests for anatomy knowledge and spatial ability, followed by access to either the 3D online learning module or the gross anatomy laboratory. Participants completed a second knowledge test prior to accessing the other learning modality. Participants in both groups scored significantly higher on Quiz 1 than on the Pretest knowledge assessment (W = 47, P < 0.01; W = 30, P < 0.01). Students who initially accessed the 3D online resources scored significantly better on the Quiz 1 than students who accessed the gross anatomy resources (W = 397.5, P < 0.01). Scores significantly improved on Quiz 2 for participants who accessed the 3D learning module following exposure to the cadaveric resources (W = 94, P < 0.01). After exposure to both learning modalities, there were no significant differences between groups. Significant positive correlations were found between participants' spatial ability score and their performance on the Pretest, Quiz 1, and Quiz 2 assessments (r = 0.22, P = 0.04; r = 0.25, P = 0.02; r = 0.26, P = 0.02). These preliminary results found students appreciated working with the 3D e-learning module, and their learning outcomes significantly improved after accessing the resource. Anat Sci Educ 9: 431-439. (c) 2016 American Association of Anatomists. PMID- 26990133 TI - Insights into the mechanisms underlying colonic motor patterns. AB - In recent years there have been significant technical and methodological advances in our ability to record the movements of the gastrointestinal tract. This has led to significant changes in our understanding of the different types of motor patterns that exist in the gastrointestinal tract (particularly the large intestine) and in our understanding of the mechanisms underlying their generation. Compared with other tubular smooth muscle organs, a rich variety of motor patterns occurs in the large intestine. This reflects a relatively autonomous nervous system in the gut wall, which has its own unique population of sensory neurons. Although the enteric nervous system can function independently of central neural inputs, under physiological conditions bowel motility is influenced by the CNS: if spinal pathways are disrupted, deficits in motility occur. The combination of high resolution manometry and video imaging has improved our knowledge of the range of motor patterns and provided some insight into the neural and mechanical factors underlying propulsion of contents. The neural circuits responsible for the generation of peristalsis and colonic migrating motor complexes have now been identified to lie within the myenteric plexus and do not require inputs from the mucosa or submucosal ganglia for their generation, but can be modified by their activity. This review will discuss the recent advances in our understanding of the different patterns of propagating motor activity in the large intestine of mammals and how latest technologies have led to major changes in our understanding of the mechanisms underlying their generation. PMID- 26990136 TI - Cervical cerclage for preterm birth prevention in twin gestation with short cervix: a retrospective cohort study. AB - OBJECTIVE: To determine if cervical cerclage reduces the rate of spontaneous early preterm birth in cases of dichorionic-diamniotic (DCDA) twin gestation with an ultrasound-detected short cervix. METHODS: This was a retrospective cohort study of 40 consecutive DCDA twin gestations at Saint Peter's University Hospital from November 2006 to November 2014 in which cervical cerclage was performed for an ultrasound-determined cervical length of 1-24 mm at 16-24 weeks' gestation. The cases were matched with 40 controls without cerclage for cervical length and gestational age at cervical assessment. The primary outcome measure was spontaneous birth < 32 weeks. RESULTS: There was no difference between the two groups in maternal age, body mass index (BMI), cigarette smoking, use of in-vitro fertilization (IVF), parity and prior spontaneous preterm birth. There were more Caucasian women among the controls compared with cases. In the cases, compared with controls, spontaneous delivery < 32 weeks was significantly less frequent (20.0% vs 50.0%; relative risk, 0.40 (95% CI, 0.20-0.80)). In the prediction of spontaneous delivery < 32 weeks, logistic regression analysis demonstrated that the risk was reduced with the insertion of cervical cerclage (odds ratio, 0.22 (95% CI, 0.058-0.835); P = 0.026), corrected for maternal age, BMI, racial origin, cigarette smoking, IVF, parity and previous preterm birth. CONCLUSION: In DCDA twin gestation with a short cervix, treatment with cervical cerclage may reduce the rate of early preterm birth. The findings suggest the need for adequate randomized controlled trials on cerclage in twin gestations with a short cervix. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26990137 TI - Ultrasound-guided fine needle aspiration cytology of gallbladder lesions: a study of 596 cases. AB - OBJECTIVE: Fine needle aspiration (FNA) is not a commonly performed procedure for gallbladder lesions for fear of causing biliary peritonitis; hence data on gallbladder cytology is scarce. The aims of the present study were to evaluate the diagnostic application of ultrasound-guided (US) FNA cytology in the pre operative diagnosis of neoplastic as well as non-neoplastic lesions of the gallbladder and to review the cytomorphological spectrum of gallbladder lesions encountered along with various diagnostic difficulties that can arise during reporting. METHODS: The study was carried out on 596 patients with gallbladder lesions in whom US-guided FNA was performed over a 5-year period. In 130 cases, simultaneous aspirations from other organs were done. The histological correlation was available in 32 cases. No major complications such as haemorrhage, peritonitis, etc. were encountered related to the procedure. RESULTS: The majority were mass lesions whereas in 73 cases (12.2%) only focal or diffuse gallbladder wall thickening was present. Cytological examination of 596 cases revealed malignancy in 462 (77.6%), 26 (4.4%) suspicious of malignancy, 23 (3.8%) inflammatory lesion, 29 negative (4.8%) and 56 cases showed necrosis only or were inadequate for any definite opinion. The lesions diagnosed on FNA cytology included carcinoma (predominantly adenocarcinoma), xanthogranulomatous cholecystitis (XGC), acute suppurative inflammation and tuberculosis. Of 26 with adequate cytology, 24 were accurate with respect to malignant (including one suspicious FNA) versus benign: one false positive and one false negative both involved xanthogranulomatous change. CONCLUSION: The present study is the largest series evaluating the role of US-guided FNA in the diagnosis of gallbladder lesions. It is a safe, rapid, reliable, cost-effective and reasonably accurate method for diagnosing gallbladder lesions. FNA should always be attempted in cases with a mass lesion. PMID- 26990138 TI - Persistent Multiyear Control of Relapsed T-Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report. AB - There are few therapeutic options for patients with T-cell acute lymphoblastic leukemia (T-ALL) who have recurrent disease after initial matched sibling hematopoietic stem cell transplantation. While a second hematopoietic stem cell transplant (HSCT) from a haploidentical donor offers the conceptual possibility of greater graft versus leukemia effect, there is minimal literature to describe the efficacy of this approach in recurrent pediatric T-ALL. We present the case of a now 9-year-old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life. PMID- 26990139 TI - RP-CARS reveals molecular spatial order anomalies in myelin of an animal model of Krabbe disease. AB - Krabbe disease (KD) is a rare demyelinating sphingolipidosis, often fatal in the first years of life. It is caused by the inactivation of the galactocerebrosidase (GALC) enzyme that causes an increase in the cellular levels of psychosine considered to be at the origin of the tissue-level effects. GALC is inactivated also in the Twitcher (TWI) mouse: a genetic model of KD that is providing important insights into the understating of the pathogenetic process and the development of possible treatments. In this article an innovative optical technique, RP-CARS, is proposed as a tool to study the degree of order of the CH2 bonds inside the myelin sheaths of TWI-mice sciatic-nerve fibres. RP-CARS, a recently developed variation of CARS microscopy, is able to combine the intrinsic chemical selectivity of CARS microscopy with molecular-bond-spatial-orientation sensibility. This is the first time RP-CARS is applied to the study of a genetic model of a pathology, leading to the demonstration of a post-onset progressive spatial disorganization of the myelin CH2 bonds. The presented result could be of great interest for a deeper understanding of the pathogenic mechanisms underlying the human KD and, moreover, it is an additional proof of the experimental validity of this microscopy technique. RP-CARS image (2850 cm-1 , CH2 bonds) of a sciatic-nerve optical longitudinal section from a Twitcher P23 (symptomatic) mouse. Scale bar: 10 microns. The image was constructed by colour-mapping the degree of molecular order of the CH2 bonds inside the myelin walls, as displayed in the colour bar on the right. PMID- 26990140 TI - Potential Future Pharmacological Treatment of Bladder Dysfunction. AB - In the last decades, a number of new antimuscarinic drugs have been introduced for treatment of the overactive bladder (OAB), defined symptomatically (OAB syndrome) or urodynamically (detrusor overactivity). Recently, three new drug principles have been approved for clinical use, the beta3 -adrenoceptor agonist, mirabegron, the phosphodiesterase-5 inhibitor, tadalafil and the blocker of afferent and efferent nerves, botulinum toxin. However, new alternatives are continuously being explored. OAB is a filling disorder, and ATP is involved in the generation of afferent impulses. One way of blocking the ATP afferent pathway is through the use of P2X3 receptor antagonists. In animal models, this strategy appears to work very well, but whether it translates effectively to man remains to be established. Evidence suggests that components of the endocannabinoid system are involved in regulation of bladder function. Clinical studies of cannabinoid extracts on LUTS are scarce and essentially restricted to patients with MS, and the results have so far not been convincing. Amplification of endocannabinoid activity by inhibiting their degradation via fatty acid amide hydrolase inhibitors may be an attractive approach, but no clinical experiences in OAB have been reported. Studies of the lower urinary tract have indicated that several transient receptor potential (TRP) channels, including TRPV1, TRPV2, TRPV4, TRPM8 and TRPA1, are expressed in the bladder and may act as sensors of stretch and/or chemical irritation. Animal studies have shown that inhibition of these pathways can be effective for the reduction in bladder activity. However, the roles of these channels for normal function and in pathological states have not been established, and so far adverse effects (hyperthermia) have hampered development of antagonists. PMID- 26990141 TI - Micro-CT evaluation of several glide path techniques and ProTaper Next shaping outcomes in maxillary first molar curved canals. AB - AIM: To evaluate the ability of ProGlider instruments, PathFiles and K-files to maintain canal anatomy during glide path preparation using X-ray computed micro tomography (micro-CT). METHODOLOGY: Forty-five extracted maxillary first permanent molars were selected. Mesio-buccal canals were randomly assigned (n = 15) to manual K-file, PathFile or ProGlider groups for glide path preparation. Irrigation was achieved with 5% NaOCl and 10% EDTA. After glide path preparation, each canal was shaped with ProTaper Next X1 and X2 to working length. Specimens were scanned (isotropic voxel size 9.1 MUm) for matching volumes and surface areas and post-treatment analyses. Canal volume, surface area, centroid shift, canal geometry variation through ratio of diameter ratios and ratio of cross sectional areas were assessed in the apical and coronal levels and at the point of maximum canal curvature. One-way factorial anovas were used to evaluate the significance of instrument in the various canal regions. RESULTS: Post-glide path analysis revealed that instrument factor was significant at the apical level for both the ratio of diameter ratios and the ratio of cross-sectional areas (P < 0.001), with an improved maintenance of root canal geometry by ProGlider and PathFile. At the coronal level and point of maximum canal curvature, ProGlider demonstrated a tendency to pre-flare the root canal compared with K-file and PathFile. PathFile and ProGlider demonstrated a significantly lower centroid shift compared with K-file at the apical level (P = 0.023). Post-shaping analysis demonstrated a more centred preparation of ProGlider, compared with PathFile and K-files, with no significant differences for other parameters. CONCLUSIONS: Use of ProGlider instruments led to less canal transportation than PathFiles and K files. PMID- 26990143 TI - Discovery of HLA-B*58:77, a novel HLA-B*58 variant, in a Taiwanese blood donor. AB - One nucleotide substitution at residue 506 of HLA-B*58:01:01:01 results in a novel allele, HLA-B*58:77. PMID- 26990142 TI - The effect of mentoring on clinical perioperative competence in operating room nursing students. AB - AIMS AND OBJECTIVES: The aim of this study was to investigate the effects of mentoring on the clinical perioperative competence of nursing operating room students in Iran. BACKGROUND: Mentoring is an essential part of clinical education, which has been studied in different populations of students. However, there is a need to assess its effectiveness in operating room students' competence. DESIGN: A randomised controlled trial was performed. METHODS: Sixty nursing operating room students were randomly assigned to experimental and control groups. Both the control and experimental groups had routine training in the form of faculty supervision. The experimental group had an additional mentoring program. Using the Persian Perceived Perioperative Competence Scale Revised, clinical competence was compared between the two groups, before and after the intervention. Using SPSS 19, descriptive and inferential statistics, including chi-square and t-tests, were conducted. RESULTS: In the experimental group, the difference between the mean scores of clinical competence before (19.43 +/- 2.80) and after (27.86 +/- 1.87) the intervention was significant (p <= 0.001). After intervention, the difference between the mean scores of the control (3.9 +/- 0.15) and experimental (8.61 +/- 0.68) groups was significant (p <= 0.003). CONCLUSION: Findings affirmed the positive effect of mentorship programmes on clinical competence in nursing operating room students. RELEVANCE TO CLINICAL PRACTICE: Mentoring is an effective method for preparing nursing students in practice. Health care systems may improve as a result of staff student relationships that ultimately increase the quality care for patients. PMID- 26990144 TI - Diuretic usage for protection against end-organ damage in liver cirrhosis and heart failure. AB - Volume overload is common in liver cirrhosis, heart failure, and chronic kidney disease, being an independent risk factor for mortality. Loop diuretics have been widely used for treating volume overload in these patients. However, there is a tendency to increase the dose of loop diuretics partly because of diuresis resistance. Neurohormonal factors are also enhanced in these patients, which play a role in volume overload and organ ischemia. Loop diuretics cannot improve neurohormonal factors and could result in end-organ damage. The water diuretic tolvaptan has been approved for use for volume overload in heart failure and liver cirrhosis. Despite causing similar increases in urine volume, its characteristics differ from those of loop diuretics. Renal blood flow is maintained with tolvaptan but decreased with furosemide in heart failure patients. Neurohormonal factors and blood pressure are not markedly altered by tolvaptan administration. It is expected that these mechanisms of tolvaptan can protect against worsening renal function by volume overload diseases compared with loop diuretics. It has also been reported that some patients do not respond well to tolvaptan. Loop diuretics and tolvaptan share the same mechanism with regard to decreasing renal interstitial osmolality, which plays a fundamental role in water diuresis. Thus, a high dose of loop diuretics could result in resistance to tolvaptan, so tolvaptan should be administered before increasing the loop diuretic dose. Therefore, volume control without enhancing end-organ damage can be achieved by adding tolvaptan to a tolerable dose of Na-sparing diuretics. PMID- 26990145 TI - The Antiferromagnetic Spin Coupling in Non-Kekule Acenes-Impressive Polyradical Character Revealed by High-Level Multireference Methods. AB - Complete active space (CASSCF) and multireference (MR-CISD(Q) and MR-AQCC) calculations were performed for non-Kekule analogues of acenes, dimethylenepolycyclobutadienes, with lengths of up to eight cyclobutadiene (CBD) units. Multireference calculations predict that the most stable energy state of the system is either triplet (if there is an odd number of CBD units) or singlet (if there is an even number of CBD units) due to antiferromagnetic spin coupling, which thus violates Hund's rule in larger molecules. We also show an impressive polyradical character in the system that increases with the size of the molecule, as witnessed by more than eleven unpaired electrons in the singlet state of the molecule with eight CBD units. Together with the small energy gap between singlet and higher multiplicity energy states even above the triplet state, this demonstrates the exceptional polyradical properties of these pi-conjugated oligomeric chains. PMID- 26990147 TI - Human rhinovirus in experimental infection after peroral Lactobacillus rhamnosus GG consumption, a pilot study. AB - BACKGROUND: Data has emerged on possible beneficial effects of probiotics in respiratory tract viral infections, but it is unclear if the promising positive effects evidenced are due to a reduced viral load during infections. The aims of this work were to investigate the effect of peroral probiotic Lactobacillus rhamnosus GG (American Type Culture Collection [ATCC], Accession No. 53103) consumption on human rhinovirus (HRV) load in nasopharyngeal lavage samples in experimental HRV infection, and to correlate viral load to clinical symptoms. METHODS: Intranasal HRV A39 inoculation was performed on 59 adults, who had consumed juice enriched with live or heat-inactivated L. rhamnosus GG or control juice for 3 weeks prior to inoculation in a randomized, controlled, pilot trial setting. Nasopharyngeal lavage samples and symptom data were analyzed on day 0 before inoculation, and on days 2 and 5. Samples were subjected to quantitative HRV detection by polymerase chain reaction (PCR). RESULTS: Before inoculation 9 of 59 (15%) samples presented with another HRV strain than the studied A39. There was a tendency toward the lowest HRV loads in the L. rhamnosus GG groups and the highest in placebo group (log10 copies/mL, 95% confidence interval [CI], 6.20 [5.18 to 7.40] in live, 6.30 [4.91 to 7.08] in inactivated L. rhamnosus GG, and 7.25 [5.81 to 7.52] in placebo group, p = 0.57 in day 2) in the wild-type excluded population. The HRV load positively correlated with the symptom scores on days 2 and 5 (correlation coefficient 0.61 [p < 0.001] and 0.28 [p = 0.034], respectively). CONCLUSION: Results did not show statistical differences in viral loads in subjects using L. rhamnosus GG when compared to placebo. HRV load positively correlated with the total symptom scores. PMID- 26990148 TI - Mild and Complete Carbonyl Ligand Scission on a Mononuclear Transition Metal Complex. AB - The complete scission of the carbon-oxygen bond of carbon monoxide, while frequently observed on bulk metals and with bimetallic and cluster transition metal complexes, is unknown with monometallic systems. Reaction of a zerovalent iron bis(borylene) complex with a cyclic (alkyl)(amino)carbene revealed a highly selective intramolecular cleavage of the C-O bond of a carbonyl ligand at room temperature, leading to the formation of a highly unusual iron complex containing a base-stabilized (bora)alkylideneborane ligand. DFT investigation of the reaction mechanism suggested that the two Lewis acidic borylene boron atoms cooperate to cleave the C-O multiple bond. PMID- 26990146 TI - Gene specific epigenetic regulation of hepatic folate transport system is responsible for perturbed cellular folate status during aging and exogenous modulation. AB - SCOPE: The present study was designed to identify the molecular mechanism of folate modulation and aging on aberrant liver folate transporter system. METHODS AND RESULTS: An in vivo rat model was used, in which weanling, young and adult rats were given folate deficient diet for 3 and 5 months and after 3 months of folate deficiency, one group received physiological folate repletion (2 mg/kg diet) and another group received over supplemented folate diet (8 mg/kg diet) for another 2 months. In adult group, 3 and 5 months of folate deficiency decreased serum and tissue folate levels with decreased uptake of folate, further associated with decreased expression levels of reduced folate carrier (RFC) and increased expression levels of folate exporter (ABCG2) at both mRNA and protein levels, which in turn regulated by promoter hypermethylation of RFC and promoter hypomethylation of ABCG2 gene. CONCLUSION: Promoter hypermethylation of RFC and promoter hypomethylation of ABCG2 may be attributed to the down regulation of RFC and up regulation of ABCG2 at mRNA and protein levels in conditions of 3 and 5 months of folate deficiency in the adult group. PMID- 26990149 TI - Testing the potential of DNA barcoding in vertebrate radiations: the case of the littoral cichlids (Pisces, Perciformes, Cichlidae) from Lake Tanganyika. AB - We obtained 398 cytochrome c oxidase subunit I barcodes of 96 morphospecies of Lake Tanganyika (LT) cichlids from the littoral zone. The potential of DNA barcoding in these fishes was tested using both species identification and species delineation methods. The best match (BM) and best close match (BCM) methods were used to evaluate the overall identification success. For this, three libraries were analysed in which the specimens were categorized into Operational Taxonomic Units (OTU) in three alternative ways: (A) morphologically distinct, including undescribed, species, (B) valid species and (C) complexes of morphologically similar or closely related species. For libraries A, B and C, 73, 73 and 96% (BM) and 72, 70 and 94% (BCM) of the specimens were correctly identified. Additionally, the potential of two species delineation methods was tested. The General Mixed Yule Coalescent (GMYC) analysis suggested 70 hypothetical species, while the Automatic Barcode Gap Discovery (ABGD) method revealed 115 putative species. Although the ABGD method had a tendency to oversplit, it outperformed the GMYC analysis in retrieving the species. In most cases where ABGD suggested oversplitting, this was due to intraspecific geographical variation. The failure of the GMYC method to retrieve many species could be attributed to discrepancies between mitochondrial gene trees and the evolutionary histories of LT cichlid species. Littoral LT cichlids have complex evolutionary histories that include instances of hybridization, introgression and rapid speciation. Nevertheless, although the utility of DNA barcoding in identification is restricted to the level of complexes, it has potential for species discovery in cichlid radiations. PMID- 26990150 TI - Longitudinal quantification of the gingival crevicular fluid proteome during progression from gingivitis to periodontitis in a canine model. AB - AIM: Inflammatory periodontal disease is widespread in dogs. This study evaluated site-specific changes in the canine gingival crevicular fluid (GCF) proteome during longitudinal progression from very mild gingivitis to mild periodontitis. Periodontitis diagnosis in dogs requires general anaesthesia with associated risks and costs; our ultimate aim was to develop a periodontitis diagnostic for application in conscious dogs. The objective of this work was to identify potential biomarkers of periodontal disease progression in dogs. MATERIAL AND METHODS: Gingival crevicular fluid was sampled from a total of 10 teeth in eight dogs at three different stages of health/disease and samples prepared for quantitative mass spectrometry (data available via ProteomeXchange; identifier PXD003337). A univariate mixed model analysis determined significantly altered proteins between health states and six were evaluated by ELISA. RESULTS: Four hundred and six proteins were identified with 84 present in all samples. The prevalence of 40 proteins was found to be significantly changed in periodontitis relative to gingivitis. ELISA measurements confirmed that haptoglobin was significantly increased. CONCLUSIONS: This study demonstrates for the first time that proteins detected by mass spectrometry have potential to identify novel biomarkers for canine periodontal disease. Further work is required to validate additional biomarkers for a periodontitis diagnostic. PMID- 26990151 TI - Solution-Processable Silicon Phthalocyanines in Electroluminescent and Photovoltaic Devices. AB - Phthalocyanines and their main group and metal complexes are important classes of organic semiconductor materials but are usually highly insoluble and so frequently need to be processed by vacuum deposition in devices. We report two highly soluble silicon phthalocyanine (SiPc) diester compounds and demonstrate their potential as organic semiconductor materials. Near-infrared (lambda(EL) = 698-709 nm) solution-processed organic light-emitting diodes (OLEDs) were fabricated and exhibited external quantum efficiencies (EQEs) of up to 1.4%. Binary bulk heterojunction solar cells employing P3HT or PTB7 as the donor and the SiPc as the acceptor provided power conversion efficiencies (PCE) of up to 2.7% under simulated solar illumination. Our results show that soluble SiPcs are promising materials for organic electronics. PMID- 26990152 TI - Low parental tolerance for infant crying: an underlying factor in infant sleep problems? AB - Parenting behaviours play a major role in the evolution of infant sleep. Sleep problems in infancy have been associated with excessive parental involvement at night-time, and with shorter delays in response to infant night wakings and signalling. Infant crying and sleep problems are linked, yet little is known about the impact of parental responses to crying on infant sleep patterns. This study examined the hypothesis that lower parental tolerance for crying is associated with infant sleep problems. We studied 144 married couples divided into three groups: parents of infants suffering from night-waking problems (i.e. the clinical group), parents of infants without sleep problems and childless couples. Crying tolerance was assessed using questionnaires, audio recordings of crying infants and using a novel paradigm, in which participants were shown a video of a crying infant and asked when they would intervene. Parents in the clinical group demonstrated shorter intervention delays in the crying infant clip (group effect: P < 0.0001), and tended to attribute more distress to the crying infants compared to parents in both control groups (P < 0.05). Additionally, women demonstrated lower tolerance for infant crying on most measures compared to men. Our results suggest that parents of sleep-disturbed infants appear to have lower tolerance for infant crying, which may be a predisposition underlying their excessive involvement in soothing their infants to sleep which may lead to the development of sleep problems. These preliminary findings should be explored further to assess their clinical validity and utility. PMID- 26990153 TI - Pulse granuloma mimicking recurrent upper tract urothelial carcinoma. PMID- 26990154 TI - Understanding How DNA Enzymes Work. AB - Tied up in knots: The crystal structure of a DNA enzyme in its post-catalytic state was solved. The results provide insight into the structural possibilities for DNA and the mechanism of DNA catalysis. PMID- 26990156 TI - Determinants that govern the recognition and uptake of Escherichia coli O157 : H7 by Acanthamoeba castellanii. AB - Predation by phagocytic predators is a major source of bacterial mortality. The first steps in protozoan predation are recognition and consumption of their bacterial prey. However, the precise mechanisms governing prey recognition and phagocytosis by protists, and the identities of the molecular and cellular factors involved in these processes are, as yet, ill-characterized. Here, we show that that the ability of the phagocytic bacterivorous amoebae, Acanthamoeba castellanii, to recognize and internalize Escherichia coli, a bacterial prey, varies with LPS structure and composition. The presence of an O-antigen carbohydrate is not required for uptake of E. coli by A. castellanii. However, O1 antigen types, not O157 O-antigen types, inhibit recognition and uptake of bacteria by amoeba. This finding implies that O-antigen may function as an antipredator defence molecule. Recognition and uptake of E. coli by A. castellanii is mediated by the interaction of mannose-binding protein located on amoebae's surface with LPS carbohydrate. Phagocytic mammalian cells also use mannose-binding lectins to recognize and/or mediate phagocytosis of E. coli. Nonetheless, A. castellanii's mannose binding protein apparently displays no sequence similarity with any known metazoan mannose binding protein. Hence, the similarity in bacterial recognition mechanisms of amoebae and mammalian phagocytes may be a result of convergent evolution. PMID- 26990155 TI - Meta-analysis of the serotonin transporter promoter variant (5-HTTLPR) in relation to adverse environment and antisocial behavior. AB - Several studies have suggested an association between antisocial, aggressive, and delinquent behavior and the short variant of the serotonin transporter gene polymorphism (5-HTTLPR). Yet, genome wide and candidate gene studies in humans have not convincingly shown an association between these behaviors and 5-HTTLPR. Moreover, individual studies examining the effect of 5-HTTLPR in the presence or absence of adverse environmental factors revealed inconsistent results. We therefore performed a meta-analysis to test for the robustness of the potential interaction effect of the "long-short" variant of the 5-HTTLPR genotype and environmental adversities, on antisocial behavior. Eight studies, comprising of 12 reasonably independent samples, totaling 7,680 subjects with an effective sample size of 6,724, were included in the meta-analysis. Although our extensive meta-analysis resulted in a significant interaction effect between the 5-HTTLPR genotype and environmental adversities on antisocial behavior, the methodological constraints of the included studies hampered a confident interpretation of our results, and firm conclusions regarding the direction of effect. Future studies that aim to examine biosocial mechanisms that influence the etiology of antisocial behavior should make use of larger samples, extend to genome-wide genetic risk scores and properly control for covariate interaction terms, ensuring valid and well-powered research designs. (c) 2016 Wiley Periodicals, Inc. PMID- 26990157 TI - Hidden, but possibly significant, cause of secondary post-partum hemorrhage: Uterine artery pseudoaneurysm. PMID- 26990159 TI - Hemiscrotal agenesis: Pathogenesis and management strategies. AB - Hemiscrotal agenesis is among the rarest anomalies in scrotal development disorders. As it has only been reported in three cases, the clinical manifestations remain unclear. We report a case of hemiscrotal agenesis with ipsilateral cryptorchidism. Based on the thermal assessment of the scrotum, concurrent scrotoplasty and orchiopexy were carried out, and the scrotoplasty improved the thermal environment of the fixed left testis. Furthermore, the low expression of androgen receptor and steroid-5-alpha-reductase, alpha polypeptide 2 in the affected side of the scrotum likely resulted in the characteristics of absent scrotal rugae, and pigmentation on histological and biological analyses. For future fertility, we believe that scrotoplasty should be considered as a management option for hemiscrotal agenesis. PMID- 26990158 TI - History of psychosis and previous episodes as potential explanatory factors for neurocognitive impairment in first-treatment bipolar I disorder. AB - OBJECTIVES: Explanatory factors for the observed neurocognitive impairment in early-stage bipolar I disorder (BD-I) have received little attention. The current study investigated neurocognitive functioning in first-treatment (FT) BD-I compared to FT schizophrenia (SCZ), and healthy controls (HCs), and the effect of history of psychosis and previous episodes in the two clinical groups. METHODS: A total of 202 FT patients with BD-I (n = 101) and SCZ spectrum disorder (n = 101), in addition to HCs (n = 101), were included. A comprehensive neurocognitive test battery was used to assess verbal learning and memory, executive functioning, processing speed, and attention and working memory. Neurocognitive functioning and the effect of history of psychosis and number of previous episodes were analyzed using separate multivariate analyses of variance and correlation analysis. RESULTS: FT patients with BD-I performed intermediately between FT SCZ spectrum patients and HCs on all measures. Compared to HCs, FT BD-I showed impaired functioning across all neurocognitive domains. No differences in neurocognitive functioning were observed in psychotic versus nonpsychotic FT patients with BD-I. With the exception of an association between number of manic episodes and two measures of executive function in FT BD-I, no associations were found between number of episodes and neurocognitive performance. CONCLUSIONS: Neurocognitive impairments were present in FT BD-I, and were not explained by history of psychosis or number of previous psychotic or depressive episodes. There were indications that executive function could be associated with number of previous manic episodes. PMID- 26990162 TI - Erratum. PMID- 26990161 TI - Temporal Properties of Cone ERGs of Pikachurin Null Mutant Mouse. AB - PURPOSE: Pikachurin is an extracellular matrix-like protein located in the synaptic cleft of photoreceptors. Pikachurin null mutant (Pika-/-) mice have abnormal ON bipolar cell function. This study aimed to determine the contribution of the ON bipolar cell pathway (ON pathway) of Pika-/- mice to the flicker ERG response and, using vector analysis, identify how the contribution varies with the stimulus frequency. METHODS: Flicker ERGs were recorded from wild-type (WT), Pika-/-, and mGluR6 null mutant (mGluR6-/-) mice. The frequency of stimulation was 3.906 to 31.250 Hz. The amplitude and phase of the fundamental components were obtained by harmonic and vector model analysis. The mGluR6-/- mice were used as a model wherein the ON pathway is known to be absent. RESULTS: The amplitudes of the fundamental components of the Pika-/- mice were significantly smaller than those of WT mice for stimulation frequencies between 3.906 and 17.578 Hz. The phase of the fundamental components of the Pika-/- mice was between those of the WT and mGluR6-/- mice. Vector analyses showed that the functioning of the ON pathway of Pika-/- mice was 12% to 25% of that of the WT mice at low frequencies (i.e., <15.625 Hz); however, it was reduced to noise level at frequencies >17.578 Hz. CONCLUSIONS: Vector model analysis can determine the degree of contribution of the ON pathway of Pika-/- mice to flicker ERG response and may be useful for determining the retinal function in mice models with abnormalities of the ON pathway. PMID- 26990160 TI - The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction. AB - PURPOSE: To investigate the expression of humanin (HN) in human retinal pigment epithelial (hRPE) cells and its effect on oxidative stress-induced cell death, mitochondrial bioenergetics, and senescence. METHODS: Humanin localization in RPE cells and polarized RPE monolayers was assessed by confocal microscopy. Human RPE cells were treated with 150 MUM tert-Butyl hydroperoxide (tBH) in the absence/presence of HN (0.5-10 MUg/mL) for 24 hours. Mitochondrial respiration was measured by XF96 analyzer. Retinal pigment epithelial cell death and caspase 3 activation, mitochondrial biogenesis and senescence were analyzed by TUNEL, immunoblot analysis, mitochondrial DNA copy number, SA-beta-Gal staining, and p16INK4a expression and HN levels by ELISA. Oxidative stress-induced changes in transepithelial resistance were studied in RPE monolayers with and without HN cotreatment. RESULTS: A prominent localization of HN was found in the cytoplasmic and mitochondrial compartments of hRPE. Humanin cotreatment inhibited tBH-induced reactive oxygen species formation and significantly restored mitochondrial bioenergetics in hRPE cells. Exogenous HN was taken up by RPE and colocalized with mitochondria. The oxidative stress-induced decrease in mitochondrial bioenergetics was prevented by HN cotreatment. Humanin treatment increased mitochondrial DNA copy number and upregulated mitochondrial transcription factor A, a key biogenesis regulator protein. Humanin protected RPE cells from oxidative stress-induced cell death by STAT3 phosphorylation and inhibiting caspase-3 activation. Humanin treatment inhibited oxidant-induced senescence. Polarized RPE demonstrated elevated cellular HN and increased resistance to cell death. CONCLUSIONS: Humanin protected RPE cells against oxidative stress-induced cell death and restored mitochondrial function. Our data suggest a potential role for HN therapy in the prevention of retinal degeneration, including AMD. PMID- 26990164 TI - Overweight, Obesity, and Risk of Age-Related Macular Degeneration. AB - PURPOSE: The aim of this study was to quantify the relationship between categories of body mass index (BMI) and age-related macular degeneration (AMD) risk in different stages. METHODS: MEDLINE, EMBASE, and ISI Web of Science were searched for all eligible studies on the relationship between BMI and incident early or late AMD. The analyses were based on data extracted from study reports. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of this association, and dose-response relationship was assessed by restricted cubic spline. RESULTS: Seven prospective cohort studies with 1613 cases identified among 31,151 subjects were included. For overweight, the relationship remained insignificant for its association with both early AMD (RR = 0.92, 95% CI: 0.68-1.15; P = 0.54) and late AMD (RR = 1.09, 95% CI: 0.93-1.25; P = 0.18). A marked 32% increase in the risk of developing late AMD was noted among obese individuals (RR = 1.32, 95% CI: 1.11-1.53, P < 0.01), while obesity showed no significant association with early AMD (RR = 0.91, 95% CI: 0.74-1.08; P = 0.67). Furthermore, elevated BMI showed a linear dose response relation with AMD risk (Pnonlinearity = 0.17), and the AMD risk increased by 2% (RR = 1.02, 95% CI: 1.01-1.04) for each 1 kg/m2 increase in BMI within the overweight and obese BMI ranges. CONCLUSIONS: Excess body weight was weakly associated with increase in the risk of AMD in a dose-dependent fashion, especially for its late stage, indicating that keeping normal body weight and avoiding further weight gain may confer potential protection against this disease. PMID- 26990166 TI - Re: Rosenfeld S. et al 2016 J Pediatr Orthop. "Predicting the Presence of Adjacent Infections in Septic Arthritis in Children". PMID- 26990163 TI - Report on the National Eye Institute Audacious Goals Initiative: Regenerating the Optic Nerve. AB - The National Eye Institute (NEI) hosted a workshop on November 19, 2014, as part of the Audacious Goals Initiative (AGI), an NEI-led effort to rapidly expand therapies for eye diseases through coordinated research funding. The central audacious goal aims to demonstrate by 2025 the restoration of usable vision in humans through the regeneration of neurons and neural connections in the eye and visual system. This workshop focused on identifying promising strategies for optic nerve regeneration. Its principal objective was to solicit input on future AGI-related funding announcements, and specifically to ask, where are we now in our scientific progress, and what progress should we reach for in the coming years? A full report was generated as a white paper posted on the NEI Web site; this report summarizes the discussion and outcomes from the meeting and serves as guidance for future funding of research that focuses on optic nerve regeneration. PMID- 26990165 TI - Editorial: Pursuit of a Dual-Benefit Antigout Drug: A First Look at Arhalofenate. PMID- 26990168 TI - An Update on the CROES Ureteroscopy Global Study. PMID- 26990167 TI - Stable Encapsulation of Air in Mesoporous Silica Nanoparticles: Fluorocarbon-Free Nanoscale Ultrasound Contrast Agents. AB - While gas-filled micrometer-sized ultrasound contrast agents vastly improve signal-to-noise ratios, microbubbles have short circulation lifetimes and poor extravasation from the blood. Previously reported fluorocarbon-based nanoscale contrast agents are more stable but their contrast is generally lower owing to their size and dispersity. The contrast agents reported here are composed of silica nanoparticles of ~100 nm diameter that are filled with ~3 nm columnar mesopores. Functionalization of the silica surface with octyl groups and resuspension with Pluronic F127 create particles with pores that remain filled with air but are stable in buffer and serum. Administration of high intensity focused ultrasound (HIFU) allows sensitive imaging of the silica nanoparticles down to 10(10) particles mL(-1) , with continuous imaging for at least 20 min. Control experiments with different silica particles supported the hypothesis that entrapped air could be pulled into bubble nuclei, which can then in turn act as acoustic scatterers. This process results in very little hemolysis in whole blood, indicating potential for nontoxic blood pool imaging. Finally, the particles are lyophilized and reconstituted or stored in PBS (phosphate-buffered saline, at least for four months) with no loss in contrast, indicating stability to storage and reformulation. PMID- 26990169 TI - Binge Eating and Overweight and Obesity Among Young Adult Lesbians. AB - PURPOSE: Lesbians are more likely to be obese compared to heterosexual women, but little research has examined correlates of obesity among lesbians. The purpose of this study was to examine the association of binge eating and overweight and obesity among lesbians. METHODS: Self-identified lesbians (N = 377) between the ages of 18-30 completed an online survey. RESULTS: Binge eating was a salient predictor of both overweight and obesity after controlling for demographic variables, outness, diet, and physical activity. CONCLUSION: Health promotion and weight loss intervention programs for lesbians should assess binge eating behaviors as a possible contributor to overweight and obesity. PMID- 26990170 TI - Antimicrobial Activity of Ceftaroline Tested against Staphylococcus aureus from Surgical Skin and Skin Structure Infections in US Medical Centers. AB - BACKGROUND: Ceftaroline fosamil is a novel cephalosporin approved by the United States Food and Drug Administration (US FDA) for treatment of acute bacterial skin and skin structure infection, including those caused by methicillin resistant Staphylococcus aureus (MRSA). We evaluated the activity of ceftaroline and comparator agents tested against S. aureus isolated from surgical skin and skin structure infections (SSSI). METHODS: Clinically substantial isolates (one/patient episode) from SSSI were consecutively collected from 64 medical centers in the United States over a 6-y period (2008-2013) and tested for susceptibility by broth microdilution methods against ceftaroline and several comparator agents. RESULTS: Among 794 strains tested, 50.5% were MRSA. Ceftaroline was active against all methicillin-susceptible Staphylococcus aureus (MSSA; minimal inhibitory concentration [MIC]90, 0.25 mcg/mL) and nearly all MRSA (MIC90, 1 mcg/mL). Against MSSA, ceftaroline was 16-fold more potent than ceftriaxone (MIC90, 4 mcg/mL) and the highest ceftaroline MIC was 0.5 mcg/mL. Among MRSA, 97.5% and 100.0% of strains were inhibited at <=1 and <=2 mcg/mL of ceftaroline. Furthermore, 27.4% and 67.5% of MRSA were resistant to clindamycin and levofloxacin, respectively. Daptomycin (MIC50/90, 0.25/0.5 mcg/mL), linezolid (MIC50/90, 1/2 mcg/mL), tigecycline (MIC50/90, 0.06/0.12 mcg/mL) and vancomycin (MIC50/90, 1/2 mcg/mL) were also highly active against S. aureus strains. CONCLUSIONS: Ceftaroline exhibited potent in vitro activity against S. aureus causing SSSI in a large number of US hospitals, including MRSA. On the basis of this in vitro data, ceftaroline fosamil may represent a valuable option for treatment of surgical SSSI, and should be further evaluated as an agent for surgical prophylaxis that would cover MRSA. PMID- 26990171 TI - Lubiprostone for Opioid-Induced Constipation Does Not Interfere with Opioid Analgesia in Patients with Chronic Noncancer Pain. AB - OBJECTIVE: To determine whether lubiprostone 24 MUg twice daily (BID), administered to relieve opioid-induced constipation (OIC), affects opioid analgesia in patients with chronic noncancer pain. METHODS: Data were pooled from 3 randomized, double-blind, placebo-controlled trials of lubiprostone in adults with chronic noncancer pain receiving stable opioid analgesia and who had documented OIC. In each study, lubiprostone 24 MUg BID or placebo was administered for 12 weeks for relief of OIC using a common protocol. The Brief Pain Inventory short form (BPI-SF) was administered, and opioid use (expressed as morphine-equivalent daily dose [MEDD]) was recorded at baseline and months 1, 2, and 3. The BPI-SF provided patient scores for pain severity, the worst pain experienced in the past 24 hours, and pain interference with daily life. RESULTS: The pooled patient population (N = 1300) was predominately female (62.5%) and white (82.1%), with a mean age of 50.5 years. The MEDD was 97.5 mg (range, 5 to 3656 mg) in patients receiving placebo and 112.5 mg (range, 4 to 7605 mg) in patients treated with lubiprostone. Lubiprostone 24 MUg BID treatment did not appear to affect opioid use or pain scores; changes from baseline were not significantly different with placebo vs. lubiprostone 24 MUg BID at months 1, 2, and 3 for MEDD (P >= 0.435) and for BPI-SF scores for pain interference, pain severity, and worst pain (P >= 0.402). DISCUSSION: Lubiprostone 24 MUg BID administered for relief of OIC in patients with chronic noncancer pain does not interfere with opioid analgesia. PMID- 26990172 TI - Nanoscale devices for linkerless long-term single-molecule observation. AB - Total internal reflection fluorescence microscopy (TIRFM) can offer favorably high signal-to-noise observation of biological mechanisms. TIRFM can be used routinely to observe even single fluorescent molecules for a long duration (several seconds) at millisecond time resolution. However, to keep the investigated sample in the evanescent field, chemical surface immobilization techniques typically need to be implemented. In this review, we describe some of the recently developed novel nanodevices that overcome this limitation enabling long-term observation of free single molecules and outline their biological applications. The working concept of many devices is compatible with high throughput strategies, which will further help to establish unbiased single molecule observation as a routine tool in biology to study the molecular underpinnings of even the most complex biological mechanisms. PMID- 26990174 TI - Y chromosome diversity in a linguistic isolate (Mirandese, NE Portugal). AB - OBJECTIVES: The purpose of this study was to genetically characterize the male lineages of people who speak Mirandese, an interesting case of a linguistic relict that can still be found in the municipality of Miranda do Douro, NE Portugal. This region lies within the area of the Leonese dialects, which are remnants of the Romance dialects spoken in the Kingdom of Leon currently grouped in the Astur-Leonese linguistic continuum. We intended to disclose affinities with surrounding populations, namely from Spain where the Astur-Leonese is also spoken. METHODS: Eighty-eight unrelated males (58 from Miranda and 30 from Braganca, the broad Portuguese region where Miranda is located) were genotyped with the combined use of 17 Y chromosome short tandem repeats (Y-STRs) and a high resolution Y chromosome single nucleotide polymorphism (Y-SNPs) strategy. Moreover, 236 males from Miranda and neighboring regions, previously classified as R-M269, were also genotyped. RESULTS: R-P312 was the most frequent haplogroup in the Mirandese, followed by J-12f2.1 and T-M70. The male lineages J-12f2.1 and T-M70 were also well represented, and both were shared with descendants of Sephardic Jews. No signs of diversity reduction were detected. CONCLUSIONS: Mirandese speakers display a Y chromosome gene pool that shows a subtle differentiation from neighboring populations, mainly attributable to the assimilation of lineages ascribed to be of Jewish ancestry. Although not revealing signs of geographic/linguistic isolation, no clear affinities with other Astur-Leonese populations were detected. The results suggest that in Miranda language sharing is not accompanied by significant gene flow between populations from both sides of the political border. Am. J. Hum. Biol. 28:671 680, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990173 TI - PARP-1 inhibition influences the oxidative stress response of the human lens. AB - Poly(ADP-ribose) polymerase-1 (PARP-1) is best characterised for its involvement in DNA repair. PARP-1 activity is also linked to cell fate, confounding its roles in maintaining genome integrity. The current study assessed the functional roles of PARP-1 within human lens cells in response to oxidative stress. The human lens epithelial cell line FHL124 and whole human lens cultures were used as experimental systems. Hydrogen peroxide (H2O2) was employed to induce oxidative stress and cell death was assessed by LDH release. The functional influence of PARP-1 was assessed using targeted siRNA and chemical inhibition (by AG14361). Immunocytochemistry and western blotting were used to assess PARP-1 expression and the alkaline comet assay determined the levels of DNA strand breaks. PARP-1 was generally observed in the cell nucleus in both the FHL124 cell line and whole human lenses. PARP-1 inhibition rendered FHL124 cells more susceptible to H2O2 induced DNA strand breaks. Interestingly, reduction of PARP-1 activity significantly inhibited H2O2-induced cell death relative to control cells. Inhibition of PARP-1 in whole human lenses resulted in a reduced level of lens opacity and cell death following exposure to H2O2 relative to matched pair controls. Thus, we show that PARP-1 could play a role in the fate of human lens cells, and these first observations in human lenses suggest that it could impact on lens opacity. Further studies are required to elucidate the regulatory processes that give rise to these effects. PMID- 26990175 TI - Overweight, perceived overweight and involvement in bullying in middle adolescence. AB - Overweight is reportedly a risk factor for being bullied, and body image may mediate this association. Research on associations between overweight and bullying has so far only focused on children and early adolescents. We explored associations between actual and perceived overweight at age 15 and involvement in bullying at ages 15 and 17. A total of 2070 Finnish adolescents responded to a survey at ages 15 and 17. Self-reported weight and height, perceived weight and involvement in bullying were elicited. Being overweight at age 15 was not associated with being bullied or with being a bully at age 15 or 17. Perceived overweight among girls was associated with subsequent involvement in bullying as a bully and in feeling shunned. Weight related bullying may decrease from pre- and early adolescence to middle adolescence. The associations between perceived overweight and self-identification as a bully, and those between perceived overweight and feeling isolated may be explained by the phenomena representing psychological dysfunction. PMID- 26990176 TI - Knowledge, attitudes, and behaviors of dentists regarding child physical abuse in Jeddah, Saudi Arabia. AB - A large proportion of child physical abuse cases go undocumented and unreported. Dentists can play an important role in identifying and reporting these cases, but little has been reported about this issue in Saudi Arabia. The aims of the study were to (1) assess dentists' knowledge of child physical abuse, (2) assess dentists' attitudes towards child physical abuse, and (3) assess the behaviors of dentists in identifying and reporting child physical abuse. A cross-sectional survey of pediatric dentists, pediatric dentistry residents, and dental interns practicing at all of the dental schools in Jeddah, Saudi Arabia was conducted using an anonymous, self-administered questionnaire. The participants in current study demonstrated insufficient knowledge of the signs and symptoms of child physical abuse, actions that should be taken in suspected cases, circumstances in which to report such cases, and the legal authorities to which they should be reported. The attitudes of participants towards detecting and reporting cases were generally positive. Only 11% of the participants had suspected a case of child abuse, and only 3% of them reported it. Lack of knowledge about referral procedures and fear of anger from family members were the main causes of underreporting. In conclusion, this study showed that dentists have insufficient knowledge about child physical abuse but positive attitudes towards their role in detecting and reporting it. This topic should be covered and emphasized in dental schools' curricula, and healthcare and academic institutes must have a clear protocol to be followed if a case of abuse is suspected. PMID- 26990177 TI - CAM within a field force of countervailing powers: The case of Portugal. AB - This paper examines the extent to which the position of the medical profession and the state towards complementary and alternative medicine (CAM) practitioners has changed since the late 1990s, taking Portugal as a case study. Using Light's concept of countervailing powers, we consider the alliances, interests, rhetoric and degrees of control between these three actors over time, focussing particularly on the extent to which CAM practitioners have acted as a countervailing force in their relationship with the medical profession and the state. It also brings to the fore the position of supra-state agencies concerning CAM regulation. A critical discourse analysis was conducted on data derived from a systematic search of information dating from the late 1990s up to 2015. Our analysis suggests that CAM has emerged as an active player and a countervailing power in that it has had significant influence on the process of state policy making. The medical profession, in turn, has moved from rejecting to 'incorporating' CAM, while the state has acted as a 'broker', trying to accommodate the demands and preferences of both actors while simultaneously demonstrating its power and autonomy in shaping health policy. In sum, the history of countermoves of CAM, the medical profession and the state in recasting power relations regarding CAM regulation in Portugal has highlighted the explanatory value of Light's countervailing power theory and the need to move away from a professional dominance and corporatist approach, in which CAM has simply been seen as subjugated to the power of the medical profession and the state. PMID- 26990178 TI - Food availability and predation risk, rather than intrinsic attributes, are the main factors shaping the reproductive decisions of a long-lived predator. AB - Deciphering the causes of variation in reproductive success is a fundamental issue in ecology, as the number of offspring produced is an important driver of individual fitness and population dynamics. Little is known, however, about how different factors interact to drive variation in reproduction, such as whether an individual's response to extrinsic conditions (e.g. food availability or predation) varies according to its intrinsic attributes (e.g. age, previous allocation of resources towards reproduction). We used 29 years of reproductive data from marked female tawny owls and natural variation in food availability (field vole) and predator abundance (northern goshawk) to quantify the extent to which extrinsic and intrinsic factors interact to influence owl reproductive traits (breeding propensity, clutch size and nest abandonment). Extrinsic and intrinsic factors appeared to interact to affect breeding propensity (which accounted for 83% of the variation in owl reproductive success). Breeding propensity increased with vole density, although increasing goshawk abundance reduced the strength of this relationship. Owls became slightly more likely to breed as they aged, although this was only apparent for individuals who had fledged chicks the year before. Owls laid larger clutches when food was more abundant. When owls were breeding in territories less exposed to goshawk predation, 99.5% of all breeding attempts reached the fledging stage. In contrast, the probability of breeding attempts reaching the fledging stage in territories more exposed to goshawk predation depended on the amount of resources an owl had already allocated towards reproduction (averaging 87.7% for owls with clutches of 1-2 eggs compared to 97.5% for owls with clutches of 4-6 eggs). Overall, our results suggested that changes in extrinsic conditions (predominantly food availability, but also predator abundance) had the greatest influence on owl reproduction. In response to deteriorating extrinsic conditions (fewer voles and more goshawks), owls appeared to breed more frequently, but allocated fewer resources per breeding attempt. However, intrinsic attributes also appeared to have a relatively small influence on how an individual responded to variation in extrinsic conditions, which indicates that owl reproductive decisions were shaped by a complex series of extrinsic and intrinsic trade-offs. PMID- 26990180 TI - Solid-phase microextraction low temperature plasma mass spectrometry for the direct and rapid analysis of chemical warfare simulants in complex mixtures. AB - Solid-phase microextraction (SPME) is directly integrated with low temperature plasma ionisation mass spectrometry to rapidly detect organophosphate chemical warfare agent simulants and their hydrolysis products in chemical mixtures, including urine. In this sampling and ionization method, the fibre serves: (i) to extract molecules from their native environment, and (ii) as the ionization electrode that is used to desorb and ionize molecules directly from the SPME surface. By use of a custom fabricated SPME fibre consisting of a stainless steel needle coated with a Linde Type A (LTA) zeolitic microporous material and low temperature plasma mass spectrometry, protonated dimethyl methylphosphonate (DMMP), diethyl ethylphosphonate (DEEP) and pinacolyl methylphosphonic acid (PinMPA) can be detected at less than 100 ppb directly in water and urine. Organophosphates were not readily detected by this approach using an uncoated needle in negative control experiments. The use of the LTA coating significantly outperformed the use of a high alumina Zeolite Socony Mobil-5 (ZSM-5) coating of comparable thickness that is significantly less polar than LTA. By conditioning the LTA probe by immersion in an aqueous CuSO4 solution, the ion abundance for protonated DMMP increased by more than 300% compared to that obtained without any conditioning. Sample recovery values were between 96 and 100% for each analyte. The detection of chemical warfare agent analogues and hydrolysis products required less than 2 min per sample. A key advantage of this sampling and ionization method is that analyte ions can be directly and rapidly sampled from chemical mixtures, such as urine and seawater, without sample preparation or chromatography for sensitive detection by mass spectrometry. This ion source should prove beneficial for portable mass spectrometry applications because relatively low detection limits can be obtained without the use of compressed gases, fluid pumps, and lasers. Moreover, the ion source is compact, can be powered with a 10 V battery, and is tolerant of complex mixtures. PMID- 26990181 TI - Histone chaperones FACT and Spt6 prevent histone variants from turning into histone deviants. AB - Histone variants are specialized histones which replace their canonical counterparts in specific nucleosomes. Together with histone post-translational modifications and DNA methylation, they contribute to the epigenome. Histone variants are incorporated at specific locations by the concerted action of histone chaperones and ATP-dependent chromatin remodelers. Recent studies have shown that the histone chaperone FACT plays key roles in preventing pervasive incorporation of two histone variants: H2A.Z and CenH3/CENP-A. In addition, Spt6, another histone chaperone, was also shown to be important for appropriate H2A.Z localization. FACT and Spt6 are both associated with elongating RNA polymerase II. Based on these two examples, we propose that the establishment and maintenance of histone variant genomic distributions depend on a transcription coupled epigenome editing (or surveillance) function of histone chaperones. PMID- 26990182 TI - Magnetofluidic Tweezing of Nonmagnetic Colloids. AB - Magnetofluidic tweezing based on negative magnetophoresis and microfabricated core-shell magnetic microtips allows controlled on-demand assembly of colloids and microparticles into various static and dynamic structures such as colloidal crystals (as shown for 3.2 MUm silica particles). PMID- 26990179 TI - Identification of a selective glucocorticoid receptor modulator that prevents both diet-induced obesity and inflammation. AB - BACKGROUND AND PURPOSE: High-fat diet consumption results in obesity and chronic low-grade inflammation in adipose tissue. Whereas glucocorticoid receptor (GR) antagonism reduces diet-induced obesity, GR agonism reduces inflammation, the combination of which would be desired in a strategy to combat the metabolic syndrome. The purpose of this study was to assess the beneficial effects of the selective GR modulator C108297 on both diet-induced weight gain and inflammation in mice and to elucidate underlying mechanisms. EXPERIMENTAL APPROACH: Ten-week old C57Bl/6 J mice were fed a high-fat diet for 4 weeks while being treated with the selective GR modulator C108297, a full GR antagonist (RU486/mifepristone) or vehicle. KEY RESULTS: C108297 and, to a lesser extent, mifepristone reduced body weight gain and fat mass. C108297 decreased food and fructose intake and increased lipolysis in white adipose tissue (WAT) and free fatty acid levels in plasma, resulting in decreased fat cell size and increased fatty acid oxidation. Furthermore, C108297 reduced macrophage infiltration and pro-inflammatory cytokine expression in WAT, as well as in vitro LPS-stimulated TNF-alpha secretion in macrophage RAW 264.7 cells. However, mifepristone also increased energy expenditure, as measured by fully automatic metabolic cages, and enhanced expression of thermogenic markers in energy-combusting brown adipose tissue (BAT) but did not affect inflammation. CONCLUSIONS AND IMPLICATIONS: C108297 attenuates obesity by reducing caloric intake and increasing lipolysis and fat oxidation, and in addition attenuates inflammation. These data suggest that selective GR modulation may be a viable strategy for the reduction of diet-induced obesity and inflammation. PMID- 26990183 TI - It Takes a Village-Taming High Conflict With the "2 PC Model". AB - Prolonged litigation frequently leaves once-married and functional parents unable to communicate effectively and coparent with each other. The damage can be even more profound for never-married parents without a history of ever functioning as life partners or parenting partners. High-conflict parents often enter into parenting coordination following litigation through stipulation or court order. For some parents, this modality fails to provide enough support and containment of conflict, and postjudgment litigation continues long after the initial divorce. A clinical case study illustrates the use of an experimental, alternative dispute-resolution intervention we call "the 2 Parenting Coordinator (PC) model." The 2 PC model evolved by applying the collaborative divorce 2-coach intervention to parenting coordination for a family in which traditional parenting coordination had twice failed. The case presented involved never married parents, whose tenuous and mistrustful connection was threatening to contaminate the child's ability to have an emotionally secure relationship with her father. PMID- 26990184 TI - Effective Strategy for Conformer-Selective Detection of Short-Lived Excited State Species: Application to the IR Spectroscopy of the N1H Keto Tautomer of Guanine. AB - The ultrafast deactivation processes in the excited state of biomolecules, such as the most stable tautomers of guanine, forbid any state-of-the-art gas phase spectroscopic studies on these species with nanosecond lasers. This drawback can be overcome by grafting a chromophore having a long-lived excited state to the molecule of interest, allowing thus a mass-selective detection by nanosecond R2PI and therefore double resonance IR/UV conformer-selective spectroscopic studies. The principle is presently demonstrated on the keto form of a modified 9 methylguanine, for which the IR/UV double resonance spectrum in the C?O stretch region, reported for the first time, provides evidence for extensive vibrational couplings within the guanine moiety. Such a successful strategy opens up a route to mass-selective IR/UV spectroscopic investigations on molecules exhibiting natural chromophores having ultrashort-lived excited states, such as DNA bases, their complexes as well as peptides containing short-lived aromatic residues. PMID- 26990185 TI - Thrombocytopenia and craniotomy for tumor: A National Surgical Quality Improvement Program analysis. AB - BACKGROUND: To the authors' knowledge, the current study is the first national analysis of the association between preoperative platelet count and outcomes after craniotomy. METHODS: Patients who underwent craniotomy for tumor were extracted from the prospective National Surgical Quality Improvement Program registry (2007-2014) and stratified by preoperative thrombocytopenia, defined as mild (125,000-149,000/MUL), moderate (100,000-124,000/MUL), severe (75,000 99,000/MUL), or very severe (<75,000/MUL). Cox proportional hazards analysis was used to evaluate the association between thrombocytopenia and 30-day mortality, and multivariable logistic regression with complications and unplanned reoperation. Covariates included patient age, sex, tumor histology, American Society of Anesthesiologists class, functional status, comorbidities, and surgical time. RESULTS: A total of 14,852 patients were included in the current study and thrombocytopenia was classified as mild in 4.4% (646 patients), moderate in 2.0% (290 patients), severe in 0.7% (105 patients), or very severe in 0.4% (66 patients) of patients. The adjusted hazard of 30-day death was significantly higher for patients with moderate (6.6%; hazard ratio [HR], 2.13 [95% confidence interval (95% CI), 1.30-3.49; P = 0.003]), severe (10.5%; HR, 2.33 [95% CI, 1.18-4.60; P = 0.02]), and very severe (10.6%; HR, 3.65 [95% CI, 1.71-7.82; P = 0.001]) thrombocytopenia, compared with patients without thrombocytopenia (2.9%), with an increased effect size noted with greater thrombocytopenia. Likewise, when the platelet count was evaluated continuously, a higher platelet count was associated with a lower hazard of 30-day mortality (HR, 0.987 [95% CI, 0.981-0.993; P<.001]), developing any complication (odds ratio, 0.985 [95% CI, 0.981-0.988; P<.001]), and reoperation (odds ratio, 0.990 [95% CI, 0.983-0.994; P = .003]). Unplanned reoperation was due to intracranial hemorrhage in 53.3% of patients with moderate thrombocytopenia. CONCLUSIONS: In this National Surgical Quality Improvement Program analysis, moderate and severe thrombocytopenia were associated with mortality and reoperation after craniotomy for tumor. Cancer 2016;122:1708-17. (c) 2016 American Cancer Society. PMID- 26990186 TI - Sensory and Physicochemical Studies of Thermally Micronized Chickpea (Cicer arietinum) and Green Lentil (Lens culinaris) Flours as Binders in Low-Fat Beef Burgers. AB - Pulses are known to be nutritious foods but are susceptible to oxidation due to the reaction of lipoxygenase (LOX) with linolenic and linoleic acids which can lead to off flavors caused by the formation of volatile organic compounds (VOCs). Infrared micronization at 130 and 150 degrees C was investigated as a heat treatment to determine its effect on LOX activity and VOCs of chickpea and green lentil flour. The pulse flours were added to low-fat beef burgers at 6% and measured for consumer acceptability and physicochemical properties. Micronization at 130 degrees C significantly decreased LOX activity for both flours. The lentil flour micronized at 150 degrees C showed a further significant decrease in LOX activity similar to that of the chickpea flour at 150 degrees C. The lowering of VOCs was accomplished more successfully with micronization at 130 degrees C for chickpea flour while micronization at 150 degrees C for the green lentil flour was more effective. Micronization minimally affected the characteristic fatty acid content in each flour but significantly increased omega 3 and n-6 fatty acids at 150 degrees C in burgers with lentil and chickpea flours, respectively. Burgers with green lentil flour micronized at 130 and 150 degrees C, and chickpea flour micronized at 150 degrees C were positively associated with acceptability. Micronization did not affect the shear force and cooking losses of the burgers made with both flours. Formulation of low-fat beef burgers containing 6% micronized gluten-free binder made from lentil and chickpea flour is possible based on favorable results for physicochemical properties and consumer acceptability. PMID- 26990187 TI - gamma-Secretase Dependent Nuclear Targeting of Dystroglycan. AB - Dystroglycan is frequently lost in adenocarcinoma. alpha-dystroglycan is known to become hypoglycosylated due to transcriptional silencing of LARGE, whereas beta dystroglycan is proteolytically cleaved and degraded. The mechanism and proteases involved in the cleavage events affecting beta-dystroglycan are poorly understood. Using LNCaP prostate cancer cells as a model system, we have investigated proteases and tyrosine phosphorylation affecting beta-dystroglycan proteolysis and nuclear targeting. Cell density or phorbol ester treatment increases dystroglycan proteolysis, whereas furin or gamma-secretase inhibitors decreased dystroglycan proteolysis. Using resveratrol treatment of LNCaP cells cultured at low cell density in order to up-regulate notch and activate proteolysis, we identified significant increases in the levels of a 26 kDa beta dystroglycan fragment. These data, therefore, support a cell density-dependent gamma-secretase and furin mediated proteolysis of beta-dystroglycan, which could be notch stimulated, leading to nuclear targeting and subsequent degradation. 117: 2149-2157, 2016. (c) 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc. PMID- 26990188 TI - Exploiting the Adaptation Dynamics to Predict the Distribution of Beneficial Fitness Effects. AB - Adaptation of asexual populations is driven by beneficial mutations and therefore the dynamics of this process, besides other factors, depends on the distribution of beneficial fitness effects. It is known that on uncorrelated fitness landscapes, this distribution can only be of three types: truncated, exponential and power law. We performed extensive stochastic simulations to study the adaptation dynamics on rugged fitness landscapes, and identified two quantities that can be used to distinguish the underlying distribution of beneficial fitness effects. The first quantity studied here is the fitness difference between successive mutations that spread in the population, which is found to decrease in the case of truncated distributions, remains nearly a constant for exponentially decaying distributions and increases when the fitness distribution decays as a power law. The second quantity of interest, namely, the rate of change of fitness with time also shows quantitatively different behaviour for different beneficial fitness distributions. The patterns displayed by the two aforementioned quantities are found to hold good for both low and high mutation rates. We discuss how these patterns can be exploited to determine the distribution of beneficial fitness effects in microbial experiments. PMID- 26990189 TI - Evaluation of High Resolution Melting for MTHFR C677T Genotyping in Congenital Heart Disease. AB - BACKGROUND: High resolution melting (HRM) is a simple, flexible and low-cost mutation screening technique. The methylenetetrahydrofolate reductase (MTHFR) gene encoding a critical enzyme, potentially affects susceptibility to some congenital defects like congenital heart disease (CHD). We evaluate the performance of HRM for genotyping of the MTHFR gene C677T locus in CHD cases and healthy controls of Chinese Han population. METHODS: A total of 315 blood samples from 147 CHD patients (male72, female 75) and 168 healthy controls (male 92, female 76) were enrolled in the study. HRM was utilized to genotype MTHFR C677T locus of all the samples. The results were compared to that of PCR-RFLP and Sanger sequencing. The association of the MTHFR C677T genotypes and the risk of CHD was analyzed using odds ratio with their 95% confidence interval (CIs) from unconditional logistic regression. RESULTS: All the samples were successfully genotyped by HRM within 1 hour and 30 minutes while at least 6 hours were needed for PCR-RFLP and sequencing. The genotypes of MTHFR C677T CC, CT, and TT were 9.52%, 49.66%, and 40.82% in CHD group but 29.17%, 50% and 20.83% in control group, which were identical using both methods of HRM and PCR-RFLP, demonstrating the sensitivity and specificity of HRM were all 100%. CONCLUSION: MTHFR C677T is a potential risk factor for CHD in our local residents of Shandong province in China. HRM is a fast, sensitive, specific and reliable method for clinical application of genotyping. PMID- 26990191 TI - The Dynamic Interplay among Maternal Empathy, Quality of Mother-Adolescent Relationship, and Adolescent Antisocial Behaviors: New Insights from a Six-Wave Longitudinal Multi-Informant Study. AB - Adolescents' behavior is often a matter of concern, given their increased likelihood of enacting antisocial behaviors, which cause disruptions in the social order and are potentially harmful for the adolescents themselves and for the people around them. In this six-wave longitudinal study we sought to examine the interplay among maternal empathy, multiple indicators of mother-adolescent relationship quality (i.e., balanced relatedness, conflict, and support), and adolescent antisocial behaviors rated both by adolescents and their mothers. Participants for the current study were 497 Dutch adolescents (56.9% males) followed from age 13 to 18, and their mothers. A series of cross-lagged panel models revealed reciprocal associations between maternal empathy and mother adolescent relationship quality and between mother-adolescent relationship quality and adolescent antisocial behaviors. Interestingly, we also found some indirect effects of adolescent antisocial behaviors on maternal empathy mediated by mother-adolescent relationship quality. Overall, this study further highlights a process of reciprocal influences within mother-adolescent dyads. PMID- 26990190 TI - Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition. AB - Hexavalent chromium (CrVI) is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf) against potassium dichromate (PDC)-induced acute kidney injury (AKI) in rats. Beside, because previous studies suggest that interlukin-18 (IL-18) and insulin-like growth factor-1 (IGF-1) play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200 mg/kg/day, p.o.) or (300 mg/kg/day, p.o.); the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15 mg/kg, s.c.). PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFkappaB), IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1) levels. Moreover, normal expression IFN-gamma mRNA and enhanced expression of TNF-alpha mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA), Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through triggering FoxO1-induced cell proliferation. Moreover, the study revealed that Lf protected the kidney against Cr-induced AKI in rats and significantly showed antioxidant, anti-inflammatory, and anti-proliferative properties with down-regulation of IL-18 and IGF-1. PMID- 26990193 TI - Paediatric primary lymphoedema: a cohort of 155 children and newborns. PMID- 26990192 TI - Impact of Persistent Cytomegalovirus Infection on Dynamic Changes in Human Immune System Profile. AB - Human cytomegalovirus (HCMV) imprints the immune system after primary infection, however its effect during chronic infection still needs to be deciphered. In this study we report the variation of blood cell count along with anti-HCMV IgG and T cell responses to pp-65 and IE-1 antigens, that occurred after an interval of five years in a cohort of 25 seropositive healthy adults. We found increased anti viral IgG antibody responses and intracellular interferon-gamma secreting CD8+ T cell responses to pp-65: a result consistent with memory inflation. With the only exception of shortage in naive CD8+ T cells most memory T cell subsets as well as total CD8+ T cells, T cells, lymphocytes, monocytes and leukocytes had increased. By contrast, none of the cell types tested were found to have increased in 14 subjects stably seronegative. Rather, in addition to a shortage in naive CD8+ T cells, also memory T cell subsets and most other cell types decreased, either in a statistically significant or non-significant manner. The trend of T cell pool representation with regard to CD4/CD8 ratio was in the opposing directions depending on HCMV serology. Globally, this study demonstrates different dynamic changes of most blood cell types depending on presence or absence of HCMV infection. Therefore, HCMV plays a continual role in modulating homeostasis of blood T cells and a broader expanding effect on other cell populations of lymphoid and myeloid origin. PMID- 26990195 TI - The effect of butylphthalide on amino acid in the brain of epileptic mice. AB - BACKGROUND: To observe the effect of butylphthalide (NBP) on the amino acid content in the brain of epileptic mice. METHODS: Butylphthalide (NBP) was injected intraperitoneally into the mice, and acute epileptic mice models were made after 30 min. The change of the four amino (aspartic acid, gamma aminobutyric acid, glutamate, glycine) content in the brain of the epileptic mice was investigated. RESULTS: The contents of Glu and Glu/GABA (model group: 38.78, NBP high dose group:5.52) in the NBP high dose group were lower compared with the model group. The difference was statistically significant. CONCLUSIONS: Butylphthalide could regulate the balance of excitement and inhibition systems by reducing the contents of Glu and Glu/GABA, which might relieve seizures. PMID- 26990194 TI - Dissecting the roles of local packing density and longer-range effects in protein sequence evolution. AB - What are the structural determinants of protein sequence evolution? A number of site-specific structural characteristics have been proposed, most of which are broadly related to either the density of contacts or the solvent accessibility of individual residues. Most importantly, there has been disagreement in the literature over the relative importance of solvent accessibility and local packing density for explaining site-specific sequence variability in proteins. We show that this discussion has been confounded by the definition of local packing density. The most commonly used measures of local packing, such as contact number and the weighted contact number, represent the combined effects of local packing density and longer-range effects. As an alternative, we propose a truly local measure of packing density around a single residue, based on the Voronoi cell volume. We show that the Voronoi cell volume, when calculated relative to the geometric center of amino-acid side chains, behaves nearly identically to the relative solvent accessibility, and each individually can explain, on average, approximately 34% of the site-specific variation in evolutionary rate in a data set of 209 enzymes. An additional 10% of variation can be explained by nonlocal effects that are captured in the weighted contact number. Consequently, evolutionary variation at a site is determined by the combined effects of the immediate amino-acid neighbors of that site and effects mediated by more distant amino acids. We conclude that instead of contrasting solvent accessibility and local packing density, future research should emphasize on the relative importance of immediate contacts and longer-range effects on evolutionary variation. Proteins 2016; 84:841-854. (c) 2016 Wiley Periodicals, Inc. PMID- 26990196 TI - Central nervous system disease in childhood acute lymphoblastic leukaemia- a review. AB - Acute lymphoblastic leukaemia (ALL) is the commonest childhood malignancy. Despite therapeutic advancements, relapse of the pathlogical state in the form of central nervous system (CNS) disease remains a challenge. CNS disease appears to be present at diagnosis in at least 40% of patients. This relpase in the form of CNS disesase os one of the major hurdles in achieving complete cure. The present review article aims to discuss the important mechanisms of leukaemic entry and infiltration patterns of leukaemic cells into the CNS. Also, latest updates in the management stratagies of ALL will also be focused in the present article. PMID- 26990197 TI - KatG, the Bifunctional Catalase of Xanthomonas citri subsp. citri, Responds to Hydrogen Peroxide and Contributes to Epiphytic Survival on Citrus Leaves. AB - Xanthomonas citri subsp. citri (Xcc) is the bacterium responsible for citrus canker. This bacterium is exposed to reactive oxygen species (ROS) at different points during its life cycle, including those normally produced by aerobic respiration or upon exposition to ultraviolet (UV) radiation. Moreover, ROS are key components of the host immune response. Among enzymatic ROS-detoxifying mechanisms, catalases eliminate H2O2, avoiding the potential damage caused by this specie. Xcc genome includes four catalase genes. In this work, we studied the physiological role of KatG, the only bifunctional catalase of Xcc, through the construction and characterization of a modified strain (XcckatG), carrying an insertional mutation in the katG gene. First, we evaluated the involvement of KatG in the bacterial adaptive response to H2O2. XcckatG cultures exhibited lower catalase activity than those of the wild-type strain, and this activity was not induced upon treatment with sub-lethal doses of H2O2. Moreover, the KatG deficient mutant exhibited decreased tolerance to H2O2 toxicity compared to wild type cells and accumulated high intracellular levels of peroxides upon exposure to sub-lethal concentrations of H2O2. To further study the role of KatG in Xcc physiology, we evaluated bacterial survival upon exposure to UV-A or UV-B radiation. In both conditions, XcckatG showed a high mortality in comparison to Xcc wild-type. Finally, we studied the development of bacterial biofilms. While structured biofilms were observed for the Xcc wild-type, the development of these structures was impaired for XcckatG. Based on these results, we demonstrated that KatG is responsible for Xcc adaptive response to H2O2 and a key component of the bacterial response to oxidative stress. Moreover, this enzyme plays an important role during Xcc epiphytic survival, being essential for biofilm formation and UV resistance. PMID- 26990198 TI - The effectiveness of pulse oximetry sonification enhanced with tremolo and brightness for distinguishing clinically important oxygen saturation ranges: a laboratory study. AB - Our study examined the effectiveness of pulse oximetry sonification enhanced with acoustic tremolo and brightness to help listeners differentiate clinically relevant oxygen saturation ranges. In a series of trials lasting 30 s each, 76 undergraduate participants identified final oxygen saturation range ( TARGET: 100% to 97%; Low: 96% to 90%; Critical: 89% and below), and detected threshold transitions into and out of the target range using conventional sonification (n = 38) or enhanced sonification (n = 38). Median (IQR [range]) accuracy for range identification with the conventional sonification was 80 (70-85 [45-95])%, whereas with the enhanced sonification it was 100 (99-100 [80-100])%; p < 0.001. Accuracy for detecting threshold transitions with the conventional sonification was 60 (50-75 [30-95])%, but with the enhanced sonification it was 100 (95-100 [75-100]%; p < 0.001. Participants can identify clinically meaningful oxygen saturation ranges and detect threshold transitions more accurately with enhanced sonification than with conventional sonification. PMID- 26990200 TI - Effect of Vagus Nerve Injury on the Outcome of Antireflux Surgery: An Extensive Literature Review. AB - BACKGROUND: Vagus nerve injury (VNI) is a feared complication of antireflux surgery (ARS). The impact of VNI on the functional outcomes of ARS has not yet been evaluated systematically. The aim of this review was to evaluate the impact of VNI on functional and clinical outcome of ARS. METHODS: A systematic search was performed until March 2015, using the following online databases: MEDLINE, Embase and the Cochrane Register of Controlled Clinical Trials. Eight studies remained available for assessment. Articles were divided into 2 groups: (a) one with unintended, accidental VNI and (b) one group comparing ARS with and without intended vagotomy. RESULTS: The prevalence of unintended, accidental VNI ranged from 10 to 42% after ARS. No clear differences were seen in outcome for reflux control between the VNI and vagus nerve intact group. A higher prevalence of diarrhea, nausea and vomiting was observed in the VNI group. CONCLUSION: VNI is a feared but neglected complication of ARS. Larger prospective studies that objectively assess vagus nerve integrity before and after ARS are needed. PMID- 26990199 TI - Entamoeba Clone-Recognition Experiments: Morphometrics, Aggregative Behavior, and Cell-Signaling Characterization. AB - Studies on clone- and kin-discrimination in protists have proliferated during the past decade. We report clone-recognition experiments in seven Entamoeba lineages (E. invadens IP-1, E. invadens VK-1:NS, E. terrapinae, E. moshkovskii Laredo, E. moshkovskii Snake, E. histolytica HM-1:IMSS and E. dispar). First, we characterized morphometrically each clone (length, width, and cell-surface area) and documented how they differed statistically from one another (as per single variable or canonical-discriminant analyses). Second, we demonstrated that amebas themselves could discriminate self (clone) from different (themselves vs. other clones). In mix-cell-line cultures between closely-related (E. invadens IP-1 vs. E. invadens VK-1:NS) or distant-phylogenetic clones (E. terrapinae vs. E. moshkovskii Laredo), amebas consistently aggregated with same-clone members. Third, we identified six putative cell-signals secreted by the amebas (RasGap/Ankyrin, coronin-WD40, actin, protein kinases, heat shock 70, and ubiquitin) and which known functions in Entamoeba spp. included: cell proliferation, cell adhesion, cell movement, and stress-induced encystation. To our knowledge, this is the first multi-clone characterization of Entamoeba spp. morphometrics, aggregative behavior, and cell-signaling secretion in the context of clone-recognition. Protists allow us to study cell-cell recognition from ecological and evolutionary perspectives. Modern protistan lineages can be central to studies about the origins and evolution of multicellularity. PMID- 26990201 TI - Frequency of Cry1F resistance alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae) in Brazil. AB - BACKGROUND: The frequency of resistance alleles is a major factor influencing the rate of resistance evolution. Here, we adapted the F2 screen procedure for Spodoptera frugiperda (J. E. Smith) with a discriminating concentration assay, and extended associated statistical methods to estimate the frequency of resistance to Cry1F protein in S. frugiperda in Brazil when resistance was not rare. RESULTS: We show that F2 screen is efficient even when the resistance frequency is 0.250. It was possible to screen 517 isoparental lines from 12 populations sampled in five states of Brazil during the first half of 2012. Western Bahia had the highest allele frequency of Cry1F resistance, 0.192, with a 95% confidence interval (CI) between 0.163 and 0.220. All other states had a similar and lower frequency varying from 0.042 in Parana to 0.080 in Mato Grosso do Sul. CONCLUSION: The high frequency in western Bahia may be related to year round availability of maize, the high population density of S. frugiperda, the lack of refuges and the high adoption rate of Cry1F maize. Cry1F resistance alleles were not rare and occurred at frequencies that have already compromised the useful life of TC1507 maize in western Bahia. (c) 2016 Society of Chemical Industry. PMID- 26990202 TI - Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity. AB - Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016. PMID- 26990203 TI - Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption. AB - Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (MUCT), three point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and beta-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious anabolic and anticatabolic effects. This study not only enriches our basic knowledge about bone quality and bone turnover mechanisms in leptin receptor-deficient animals, but also advances our understanding of the skeletal sensitivity of leptin-resistant db/db mice in response to external mechanical stimulation. (c) 2016 American Society for Bone and Mineral Research. PMID- 26990205 TI - Food peptidomics of in vitro gastrointestinal digestions of partially purified bovine hemoglobin: low-resolution versus high-resolution LC-MS/MS analyses. AB - Consumers and governments have become aware how the daily diet may affect the human health. All proteins from both plant and animal origins are potential sources of a wide range of bioactive peptides and the large majority of those display health-promoting effects. In the meat production food chain, the slaughterhouse blood is an inevitable co-product and, today, the blood proteins remain underexploited despite their bioactive potentiality. Through a comparative food peptidomics approach we illustrate the impact of resolving power, accuracy, sensitivity, and acquisition speed of low-resolution (LR)- and high-resolution (HR)-LC-ESI-MS/MS on the obtained peptide mappings and discuss the limitations of MS-based peptidomics. From in vitro gastrointestinal digestions of partially purified bovine hemoglobin, we have established the peptide maps of each hemoglobin chain. LR technique (normal bore C18 LC-LR-ESI-MS/MS) allows us to identify without ambiguity 75 unique peptides while the HR approach (nano bore C18 LC-HR-ESI-MS/MS) unambiguously identify more than 950 unique peptides (post translational modifications included). Herein, the food peptidomics approach using the most performant separation methods and mass spectrometers with high resolution capabilities appears as a promising source of information to assess the health potentiality of proteins. PMID- 26990204 TI - Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA DRB1*15:01 Status. AB - Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients. PMID- 26990206 TI - Promoting improved family caregiver health literacy: evaluation of caregiver communication resources. AB - OBJECTIVES: Family caregivers of cancer patients have a vital role in facilitating and sharing information about cancer, revealing a need to develop caregiver health literacy skills to support caregiver communication. The goal of this study was to investigate caregiver print materials and develop and assess a new caregiver communication resource titled A Communication Guide for CaregiversTM . METHODS: Using a model of six domains of caregiver health literacy skills, print cancer education materials were collected and evaluated for caregiver communication support. A new caregiver communication resource was also developed and assessed by caregivers and healthcare providers. Caregivers reviewed content and assessed utility, relatability, and reading quality. Healthcare providers also assessed whether the material would be understandable and usable for cancer caregivers. RESULTS: Only three of the 28 print materials evaluated were written at the recommended sixth grade reading level and only five addressed all six caregiver health literacy skills. Readability scores for A Communication Guide for CaregiversTM were at the sixth grade level, and caregivers reported its contents were relatable, useful, and easy to read. Healthcare providers also rated the material as easy for patient/family members of diverse backgrounds and varying levels of literacy to understand and use. CONCLUSIONS: Existing print-based caregiver education materials do not address caregivers' health literacy skill needs and are aimed at a highly literate caregiving population. A Communication Guide for CaregiversTM meets health literacy standards and family caregiver and provider communication needs. The findings are relevant for healthcare professionals who provide cancer education. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990207 TI - Sequential early and delayed painful sciatic neuropathy following revision total hip arthroplasty. PMID- 26990208 TI - Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells. AB - Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. PMID- 26990209 TI - Evidence supporting a premature termination mechanism for subgenomic RNA transcription in Pelargonium line pattern virus: identification of a critical long-range RNA-RNA interaction and functional variants through mutagenesis. AB - Pelargonium line pattern virus (PLPV) is a plus-strand RNA virus that has been proposed as type species of a tentative new genus, Pelarspovirus, in the family Tombusviridae. One of the singular traits of members of this prospective genus is the production of a unique subgenomic (sg) mRNA that is structurally and functionally tricistronic. Here, we have aimed to get insights into the mechanism that governs PLPV sg mRNA transcription. A long-range RNA-RNA interaction that is critical for the process has been identified through RNA folding predictions and mutational analysis of the viral genome. Such interaction seems to occur in the plus-strand, likely acts in cis, and specifically mediates the synthesis of sg RNA-sized minus-strand. The accumulation of this RNA species is easily detectable in plants and its generation can be uncoupled from that of the plus-strand sg mRNA. All these data together with the observation that 5' ends of PLPV genomic and sg mRNAs have sequence resemblances (as expected if both act as promoters in the corresponding minus-strand), support that premature termination is the mechanism underlying PLPV sg mRNA formation. PMID- 26990210 TI - Provider Experience and the Comparative Safety of Laparoscopic and Open Colectomy. AB - OBJECTIVE: To evaluate the comparative safety of laparoscopic and open colectomy across surgeons varying in experience with laparoscopy. DATA SOURCES: National Medicare data (2008-2010) for beneficiaries undergoing laparoscopic or open colectomy. STUDY DESIGN: Using instrumental variable methods to address selection bias, we evaluated outcomes of laparoscopic and open colectomy. Our instrument was the regional use of laparoscopy in the year prior to a patient's operation. We then evaluated outcomes stratified by surgeons' annual volume of laparoscopic colectomy. PRINCIPAL FINDINGS: Laparoscopic colectomy was associated with lower mortality (OR: 0.75, 95 percent CI: 0.70-0.78) and fewer complications than open surgery (OR: 0.82, 95 percent CI: 0.79-0.85). Increasing surgeon volume was associated with better outcomes for both procedures, but the relationship was stronger for laparoscopy. The comparative safety depended on surgeon volume. High volume surgeons had 40 percent lower mortality (OR: 0.60, 95 percent CI: 0.55 0.65) and 30 percent fewer complications (OR: 0.70, 95 percent CI: 0.67-0.74) with laparoscopy. Conversely, low-volume surgeons had 7 percent higher mortality (OR: 1.07, 95 percent CI: 1.02-1.13) and 18 percent more complications (OR: 1.18, 95 percent CI: 1.12-1.24) with laparoscopy. CONCLUSIONS: This population-based study demonstrates that the comparative safety of laparoscopic and open colectomy is influenced by surgeon volume. Laparoscopic colectomy is only safer for patients whose surgeons have sufficient experience. PMID- 26990211 TI - Computerized Automatic Diagnosis of Innocent and Pathologic Murmurs in Pediatrics: A Pilot Study. AB - OBJECTIVE: Computer-aided auscultation in the differentiation of pathologic (AHA class I) from no or innocent murmurs (AHA class III) would be of great value to the general practitioner. This would allow objective screening for structural heart disease, standardized documentation of auscultation findings, and may avoid unnecessary referrals to pediatric cardiologists. Our goal was to assess the quality of a novel computerized algorithm that automatically classifies murmurs in phonocardiograms (PCGs) acquired in a pediatric population. DESIGN: This is a pilot study testing the ability of a novel computerized algorithm to accurately diagnose PCGs compared with interpreted echocardiograms as a gold standard. SETTING: This study was performed in pediatric cardiology clinics at a tertiary care hospital. PATIENTS: All incoming patients were recruited, including patients with no murmurs, innocent murmurs, and pathologic murmurs (106 patients). INTERVENTION: Using an electronic stethoscope, PCGs were acquired by the pediatric cardiologist from each patient. The PCGs were analyzed by the algorithm and diagnoses were compared with findings by echocardiograms interpreted by pediatric cardiologists which were used as the gold standard. OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS: When compared with echocardiography as a gold standard in diagnosing murmurs, the computerized algorithm tested on N=34 PCGs, yielded a sensitivity of 87% and specificity of 100%, a positive predictive value of 100%, negative predictive value of 90% and an accuracy of 94%. CONCLUSION: With echocardiogram as a gold standard, this computerized algorithm can detect pathologic murmurs with high sensitivity, specificity and accuracy, comparable to if not better than published results of pediatric cardiologists and neonatologists. This study confirms the high quality and "real-world" robustness of a novel computational algorithm in the assessment of pediatric murmurs. PMID- 26990212 TI - Adjunct Histamine Blockers as Premedications to Prevent Carboplatin Hypersensitivity Reactions. AB - OBJECTIVE: The objective of this study was to evaluate the impact of premedications given as an adjunct to carboplatin on the incidence of hypersensitivity reactions in women with ovarian cancer. Medications of interest include a histamine1 (H1 ) and histamine2 (H2 ) blocker in addition to dexamethasone. METHODS: This was a retrospective chart review evaluating the addition of an H1 and H2 blocker in addition to dexamethasone as standard premedications on the incidence of carboplatin hypersensitivity reactions (CHRs) in women with ovarian cancer. MAIN RESULTS: The odds ratio for premedication use was 0.46 with a 95% confidence interval (0.17-1.27), suggesting that patients with premedication use had approximately half the risk of CHR compared with patients without premedication. The overall incidence of CHRs decreased from 7.9% at baseline to 3.2% after the addition of premedications. The incidence of CHRs was 5.2% in 58 patients with recurrent or progressive disease compared with 2.1% in 96 newly diagnosed patients. Lifetime dose greater than 3377 mg, number of cycles more than six, and progressive or recurrent disease were predictive factors of CHR in women with ovarian cancer. PRINCIPAL CONCLUSIONS: Total lifetime exposure to carboplatin remains the greatest predictive factor of CHR in women with ovarian cancer. Although data analysis indicates the addition of premedications for all ovarian cancer patients receiving carboplatin did not result in a statistically significant reduction in CHRs, a patient benefit in CHR reduction was observed. A prospective study is needed to confirm these findings. PMID- 26990213 TI - Prenatal diagnosis of periventricular nodular heterotopia in borderline ventriculomegaly using sonography and magnetic resonance imaging. AB - Periventricular nodular heterotopia (PNH) is usually missed on prenatal sonographic examinations, even on targeted scans. Irregular ventricular walls on axial view and irregular square-shaped lateral ventricles on coronal view are suggestive of PNH in the early third trimester. To achieve an early prenatal diagnosis, it is important to keep in mind the possible coexistence of PNH with brain malformations such as ventriculomegaly, posterior fossa anomalies, or agenesis of corpus callosum. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:510-513, 2016. PMID- 26990214 TI - Compartmentalized gene regulatory network of the pathogenic fungus Fusarium graminearum. AB - Head blight caused by Fusarium graminearum threatens world-wide wheat production, resulting in both yield loss and mycotoxin contamination. We reconstructed the global F. graminearum gene regulatory network (GRN) from a large collection of transcriptomic data using Bayesian network inference, a machine-learning algorithm. This GRN reveals connectivity between key regulators and their target genes. Focusing on key regulators, this network contains eight distinct but interwoven modules. Enriched for unique functions, such as cell cycle, DNA replication, transcription, translation and stress responses, each module exhibits distinct expression profiles. Evolutionarily, the F. graminearum genome can be divided into core regions shared with closely related species and variable regions harboring genes that are unique to F. graminearum and perform species specific functions. Interestingly, the inferred top regulators regulate genes that are significantly enriched from the same genomic regions (P < 0.05), revealing a compartmentalized network structure that may reflect network rewiring related to specific adaptation of this plant pathogen. This first-ever reconstructed filamentous fungal GRN primes our understanding of pathogenicity at the systems biology level and provides enticing prospects for novel disease control strategies involving the targeting of master regulators in pathogens. The program can be used to construct GRNs of other plant pathogens. PMID- 26990216 TI - Synthesis of the First Example of the 12-Vertex-closo/12-Vertex-nido Biscarborane Cluster by a Metal-Free B-H Activation at a Phosphorus(III) Center. AB - An unusual 12-vertex-closo-C2 B10 /12-vertex-nido-C2 B10 biscarborane cluster was synthesized through an unprecedented regioselective metal-free B-H activation by a sterically hindered P(III) center under mild conditions accompanied by cage opening rearrangement. A combination of the electron-accepting properties of a carborane cage and steric enforcement of close interatomic contacts represent a new synthetic strategy for the activation of strong B-H bonds in carboranes. PMID- 26990215 TI - The Role of Response Inhibition in Medicated and Unmedicated Obsessive-Compulsive Disorder Patients: Evidence from the Stop-Signal Task. AB - BACKGROUND: Numerous studies have investigated response inhibition (RI) in obsessive-compulsive disorder (OCD), with many reporting that OCD patients demonstrate deficits in RI as compared to controls. However, reported effect sizes tend to be modest and results have been inconsistent, with some studies finding intact RI in OCD. To date, no study has examined the effect of medications on RI in OCD patients. METHODS: We analyzed results from a stop signal task to probe RI in 65 OCD patients (32 of whom were medicated) and 58 healthy controls (HCs). RESULTS: There was no statistically significant difference in stop-signal reaction time between the OCD group and the HC group, or between the medicated and unmedicated OCD patients. However, variability was significantly greater in the medicated OCD group compared to the unmedicated group. CONCLUSIONS: These results indicate that some samples of OCD patients do not have deficits in RI, making it unlikely that deficient RI underlies repetitive behaviors in all OCD patients. Future research is needed to fully elucidate the impact of medication use on stop-signal performance. Implications for future research on the cognitive processes underlying repetitive thoughts and behaviors are discussed. PMID- 26990217 TI - A Bis(methylpiperazinylstyryl)phenanthroline as a Fluorescent Ligand for G Quadruplexes. AB - G-quadruplex (G4)-forming sequences are prevalent in the genome and are considered to play important roles in gene regulation, and hence have been viewed as potential therapeutic targets in oncology. However, the structures and functions of most G4s in the genome are poorly understood. Therefore, the development of fluorescent probes and ligands for G4s is important for G4 research and drug discovery. Herein, we report a new G4 ligand, 2,9-bis[4-(4 methylpiperazin-1-yl)styryl]-1,10-phenanthroline (BMSP), which was synthesized by a simple process. BMSP exhibits almost no fluorescence in aqueous buffer. The interaction of BMSP with G4s greatly enhances its fluorescence with a large Stokes' shift of 160 nm. Antiparallel human telomeric G4s exhibit the strongest binding affinity (Kd ~0.13 MUm) to BMSP and induce a fluorescence enhancement of up to 150-fold. BMSP binds to G4s through pi-pi stacking on the terminal G quartets. BMSP can enter live cells, and it strongly inhibits the growth of cancer cells rather than causing cell death. Our results suggest that BMSP has the potential to serve both as a fluorescent probe for some G4s and as a chemotherapeutic agent for cancer treatment. PMID- 26990218 TI - DOPC-Detergent Conjugates: Fusogenic Carriers for Improved In Vitro and In Vivo Gene Delivery. AB - Phospholipid-detergent conjugates are proposed as fusogenic carriers for gene delivery. Eleven compounds are prepared and their properties are investigated. The ability of the conjugates to promote fusion with a negatively charged model membrane is determined. Their DNA delivery efficiency and cytotoxicity are assessed in vitro. Lipoplexes are administered in the mouse lung, and transgene expression Indeterminate inflammatory activity are measured. The results show that conjugation of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with C12 E4 produces a carrier that can efficiently deliver DNA to cells, with negligible associated toxicity. Fusogenicity of the conjugates shows good correlation with in vitro transfection efficiency and crucially depends on the length of the polyether moiety of the detergent. Finally, DOPC-C12 E4 reveals highly potent for in vivo DNA delivery and favorably compares to GL67A, the current golden standard for gene delivery to the airway, opening the way for further promising developments. PMID- 26990219 TI - Locating Purity within Corruption Rumors: Narratives of HPV Vaccination Refusal in a Peri-urban Community of Southern Romania. AB - This article locates the symbolic construction of "corrupted purity"-as a key assertion in Romanian parents' HPV vaccination refusal narratives-within a multiplicity of entangled rumors concerning reproduction and the state. Romania's unsuccessful HPV vaccination campaign is not unique. However, the shifting discourses around purity and corruption-through which some parents conveyed anxieties about their daughters being targeted for the vaccine-place a particular twist on the Romanian case of resisting the HPV vaccination. Parental discourses took the form of clusters of rumors about state medicine's failure to provide adequate reproductive health care, additive-laden foods, and exposure to radioactive contamination. In these rumors, corruption becomes literally embodied, through ingestion, consumption, contact, or inoculation. Parental discourses about what is being injected into their daughters' pristine bodies express their uncertainty around navigating the unsettled post-socialist medical landscape. PMID- 26990220 TI - A systematic review and meta-analysis of workplace intervention strategies to reduce sedentary time in white-collar workers. AB - Prolonged sedentary behaviour has been associated with various detrimental health risks. Workplace sitting is particularly important, providing it occupies majority of total daily sedentary behaviour among desk-based employees. The aim of this systematic review and meta-analysis was to examine the effectiveness of workplace interventions overall, and according to different intervention strategies (educational/behavioural, environmental and multi-component interventions) for reducing sitting among white-collar working adults. Articles published through December 2015 were identified in five online databases and manual searches. Twenty-six controlled intervention studies published between 2003 and 2015 of 4568 working adults were included. All 26 studies were presented qualitatively, and 21 studies with a control group without any intervention were included in the meta-analysis. The pooled intervention effect showed a significant workplace sitting reduction of -39.6 min/8-h workday (95% confidence interval [CI]: -51.7, -27.5), favouring the intervention group. Multi-component interventions reported the greatest workplace sitting reduction (-88.8 min/8-h workday; 95% CI: -132.7, -44.9), followed by environmental (-72.8 min/8-h workday; 95% CI: -104.9, -40.6) and educational/behavioural strategies -15.5 min/8-h workday (95% CI:-22.9,-8.2). Our study found consistent evidence for intervention effectiveness in reducing workplace sitting, particularly for multi component and environmental strategies. Methodologically rigorous studies using standardized and objectively determined outcomes are warranted. (c) 2016 World Obesity. PMID- 26990221 TI - The Emotional Child Witness Effect Survives Presentation Mode. AB - The emotional witness effect - the phenomenon whereby people are affected by the emotional manner in which a witness presents testimony - constitutes a possible source of wrongful decisions in legal contexts. One stereotypical view of abused children is that they should be sad when talking about their experiences of maltreatment, whereas children may in fact express a variety of emotional expressions when talking about abusive events. This raises the question as to whether there is an optimal mode in which to present child victim testimony that could reduce the possible influence of displayed emotions. In the present study, mock police interviews were carried out with female child actors, role-playing the victims of physical abuse by their stepfather, telling the same story with four emotional expressions (neutral, sad, angry, or positive). Laypersons (N = 465) were presented with the interviews as transcripts with the emotional reactions of the child witness noted, audio recordings, or videotaped recordings. Participants then rated the credibility of the victim witness. Replicating previous results, the "sad" expression elicited the highest credibility ratings across all modes of presentations. Presentation mode affected ratings of credibility, with the transcript versions resulting in the highest ratings. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990222 TI - Autonomy is a Right, Not a Feat: How Theoretical Misconceptions have Muddled the Debate on Dynamic Consent to Biobank Research. AB - Should people be involved as active participants in longitudinal medical research, as opposed to remaining passive providers of data and material? We argue in this article that misconceptions of 'autonomy' as a kind of feat rather than a right are to blame for much of the confusion surrounding the debate of dynamic versus broad consent. Keeping in mind two foundational facts of human life, freedom and dignity, we elaborate three moral principles - those of autonomy, integrity and authority - to better see what is at stake. Respect for autonomy is to recognize the other's right to decide in matters that are important to them. Respect for integrity is to meet, in one's relationship with the other, their need to navigate the intersection between private and social life. Respect for authority is to empower the other - to help them to cultivate their responsibility as citizens. On our account, to force information onto someone who does not want it is not to respect that person's autonomy, but to violate integrity in the name of empowerment. Empowerment, not respect for autonomy, is the aim that sets patient-centred initiatives employing a dynamic consent model apart from other consent models. Whether this is ultimately morally justified depends on whether empowerment ought to be a goal of medical research, which is questionable. PMID- 26990223 TI - Molecular insights into cell toxicity of a novel familial amyloidogenic variant of beta2-microglobulin. AB - The first genetic variant of beta2 -microglobulin (b2M) associated with a familial form of systemic amyloidosis has been recently described. The mutated protein, carrying a substitution of Asp at position 76 with an Asn (D76N b2M), exhibits a strongly enhanced amyloidogenic tendency to aggregate with respect to the wild-type protein. In this study, we characterized the D76N b2M aggregation path and performed an unprecedented analysis of the biochemical mechanisms underlying aggregate cytotoxicity. We showed that, contrarily to what expected from other amyloid studies, early aggregates of the mutant are not the most toxic species, despite their higher surface hydrophobicity. By modulating ganglioside GM1 content in cell membrane or synthetic lipid bilayers, we confirmed the pivotal role of this lipid as aggregate recruiter favouring their cytotoxicity. We finally observed that the aggregates bind to the cell membrane inducing an alteration of its elasticity (with possible functional unbalance and cytotoxicity) in GM1-enriched domains only, thus establishing a link between aggregate-membrane contact and cell damage. PMID- 26990224 TI - Blockade of Androgen Markers Using a Novel Betasitosterol, Thioctic Acid and Carnitine-containing Compound in Prostate and Hair Follicle Cell-based Assays. AB - Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990225 TI - Isotopic insights into methane production, oxidation, and emissions in Arctic polygon tundra. AB - Arctic wetlands are currently net sources of atmospheric CH4 . Due to their complex biogeochemical controls and high spatial and temporal variability, current net CH4 emissions and gross CH4 processes have been difficult to quantify, and their predicted responses to climate change remain uncertain. We investigated CH4 production, oxidation, and surface emissions in Arctic polygon tundra, across a wet-to-dry permafrost degradation gradient from low-centered (intact) to flat- and high-centered (degraded) polygons. From 3 microtopographic positions (polygon centers, rims, and troughs) along the permafrost degradation gradient, we measured surface CH4 and CO2 fluxes, concentrations and stable isotope compositions of CH4 and DIC at three depths in the soil, and soil moisture and temperature. More degraded sites had lower CH4 emissions, a different primary methanogenic pathway, and greater CH4 oxidation than did intact permafrost sites, to a greater degree than soil moisture or temperature could explain. Surface CH4 flux decreased from 64 nmol m(-2) s(-1) in intact polygons to 7 nmol m(-2) s(-1) in degraded polygons, and stable isotope signatures of CH4 and DIC showed that acetate cleavage dominated CH4 production in low-centered polygons, while CO2 reduction was the primary pathway in degraded polygons. We see evidence that differences in water flow and vegetation between intact and degraded polygons contributed to these observations. In contrast to many previous studies, these findings document a mechanism whereby permafrost degradation can lead to local decreases in tundra CH4 emissions. PMID- 26990226 TI - Foreword. PMID- 26990227 TI - Thromboelastographic evidence of inhibition of fibrinolysis after epsilon aminocaproic acid administration in a dog with suspected acute traumatic coagulopathy. AB - OBJECTIVE: To describe the thromboelastographic changes in fibrinolysis with epsilon-aminocaproic acid treatment in a dog with suspected acute traumatic coagulopathy. CASE SUMMARY: A 9-year-old female spayed Airedale Terrier was presented with multiple injuries consistent with motor vehicle trauma. After surgical repair of a diaphragmatic hernia and minor laceration of the right cranial lung lobe, the dog continued to produce copious volumes of hemorrhagic fluid from the thoracic cavity despite multiple plasma transfusions, autotransfusions, and failure to locate a definitive source of bleeding during 2 separate surgeries. epsilon-Aminocaproic acid treatment was initiated and was associated with rapid clinical improvement and diminished fibrinolysis based on a modified plasma-based thromboelastogram. NEW OR UNIQUE INFORMATION PROVIDED: This report describes thromboelastographic evidence of inhibition of fibrinolysis after epsilon-aminocaproic acid administration in a dog with suspected acute traumatic coagulopathy. Thromboelastrography may be useful in monitoring therapy with antifibrinolytic drugs. PMID- 26990228 TI - Reply to the Baader-Meinhof phenomenon in ductal carcinoma in situ of the breast. PMID- 26990231 TI - Student performance in and perceptions of a high structure undergraduate human anatomy course. AB - Human anatomy has usually been taught in a didactic fashion in colleges and universities. However, recent calls from United States governmental agencies have called for the transformation of undergraduate life sciences education to include active learning in the classroom. In addition, high structure courses have been shown to increase student engagement both in and out of the classroom and to improve student performance. Due to these reform efforts and the evidence on the benefits of these student-centered pedagogies, the goal of this study was to develop and assess a high structure college undergraduate human anatomy course with a lecture and laboratory component. The course was taught using a systems anatomy approach that required students to read the textbook and complete assignments before class, actively participate in class, and complete review quizzes after class. Results showed that teaching with high structure methods did not negatively affect any student groups (based on gender, ethnicity, or major) as measured by performance on lecture examinations and laboratory practical examinations. Students reported that reading the textbook and working with anatomical models were the most important towards helping them learn the course material and students' confidence in achieving the course goals significantly increased at the end of the course. The successful development and implementation of this course suggests that it is possible to teach human anatomy using active learning and high structure. Future studies can now be conducted to determine the contributions of specific course components to student success in high structure human anatomy courses. Anat Sci Educ 9: 516-528. (c) 2016 American Association of Anatomists. PMID- 26990230 TI - A Novel Class of Dopamine D4 Receptor Ligands Bearing an Imidazoline Nucleus. AB - Over the years, the 2-substituted imidazoline nucleus has been demonstrated to be a bioversatile structural motif. In this study, novel imidazoline derivatives bearing a 3- and/or 4-hydroxy- or methoxy-substituted phenyl ring, linked by an ethylene bridge to position 2 of an N-benzyl- or N-phenethyl-substituted imidazoline nucleus, were prepared and studied against D2 -like receptor subtypes. Binding studies highlighted that a set of N-phenethylimidazoline compounds are selective for D4 over D2 and D3 receptors. In functional assays, the 3-methoxy-substituted derivative, endowed with the highest D4 affinity value, and its 3-hydroxy analogue behaved as partial agonists with low intrinsic efficacy and as competitive D4 antagonists when tested in the presence of the D2 like receptor agonist quinpirole. Molecular docking analysis, performed using a homology model of the human D4 receptor developed using the X-ray crystal structure of the antagonist-bound human D3 receptor as a template, was in accordance with the binding results and provided useful information for the design of novel imidazoline D4 receptor ligands based on this new scaffold. PMID- 26990229 TI - Uncertainty and variability in computational and mathematical models of cardiac physiology. AB - KEY POINTS: Mathematical and computational models of cardiac physiology have been an integral component of cardiac electrophysiology since its inception, and are collectively known as the Cardiac Physiome. We identify and classify the numerous sources of variability and uncertainty in model formulation, parameters and other inputs that arise from both natural variation in experimental data and lack of knowledge. The impact of uncertainty on the outputs of Cardiac Physiome models is not well understood, and this limits their utility as clinical tools. We argue that incorporating variability and uncertainty should be a high priority for the future of the Cardiac Physiome. We suggest investigating the adoption of approaches developed in other areas of science and engineering while recognising unique challenges for the Cardiac Physiome; it is likely that novel methods will be necessary that require engagement with the mathematics and statistics community. ABSTRACT: The Cardiac Physiome effort is one of the most mature and successful applications of mathematical and computational modelling for describing and advancing the understanding of physiology. After five decades of development, physiological cardiac models are poised to realise the promise of translational research via clinical applications such as drug development and patient-specific approaches as well as ablation, cardiac resynchronisation and contractility modulation therapies. For models to be included as a vital component of the decision process in safety-critical applications, rigorous assessment of model credibility will be required. This White Paper describes one aspect of this process by identifying and classifying sources of variability and uncertainty in models as well as their implications for the application and development of cardiac models. We stress the need to understand and quantify the sources of variability and uncertainty in model inputs, and the impact of model structure and complexity and their consequences for predictive model outputs. We propose that the future of the Cardiac Physiome should include a probabilistic approach to quantify the relationship of variability and uncertainty of model inputs and outputs. PMID- 26990232 TI - Differential performance of first-trimester screening in predicting small-for gestational-age neonate or fetal growth restriction. AB - OBJECTIVE: To assess the ability of integrated first-trimester screening, combining maternal characteristics and biophysical and biochemical markers, to predict delivery of a small-for-gestational-age (SGA) neonate, and compare this with its ability to predict fetal growth restriction (FGR). METHODS: This was a prospective cohort study of singleton pregnancies undergoing routine first trimester screening. SGA was defined as birth weight (BW) < 10th percentile and FGR was defined as an ultrasound estimated fetal weight < 10th percentile plus Doppler abnormalities, or BW < 3rd percentile. Logistic regression-based predictive models were developed for predicting SGA and FGR. Models incorporated the a-priori risk from maternal characteristics, and mean arterial pressure, uterine artery Doppler, placental growth factor and soluble fms-like tyrosine kinase-1. RESULTS: In total, 9150 births were included. Of these, 979 (10.7%) qualified for a postnatal diagnosis of SGA and 462 (5.0%) for a prenatal diagnosis of FGR. For predicting SGA, the model achieved a detection rate of 35% for a false-positive rate (FPR) of 5% and 42% for a 10% FPR. The model's performance was significantly higher for predicting FGR (P < 0.001), with detection rates of 59% and 67%, for a FPR of 5% and 10%, respectively. CONCLUSION: The predictive performance of first-trimester screening for cases with growth impairment by a combination of maternal characteristics and biophysical and biochemical markers is improved significantly when a prenatal and strict definition of FGR is used rather than a postnatal definition based on BW. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26990233 TI - Hybrid Capture 2 and cobas human papillomavirus assays perform similarly on SurePath samples from women with abnormalities. AB - OBJECTIVE: In two laboratories (Departments of Pathology, Copenhagen University Hospitals of Herlev and Hvidovre), we compared cobas and Hybrid Capture 2 (HC2) human papillomavirus (HPV) assays using SurePath(r) samples from women with atypical squamous cells of undetermined significance (ASCUS) at >=30 years and women after treatment of cervical intraepithelial neoplasia (CIN). METHODS: Samples from 566 women with ASCUS and 411 women after treatment were routinely tested with HC2 and, thereafter, with cobas. Histological outcomes were retrieved from the Danish Pathology Data Base. We calculated the overall agreement between the assays, and compared their sensitivity and specificity for >=CIN2. RESULTS: In women with ASCUS, HC2 and cobas testing results were similar in the two laboratories. The overall agreement was 91% (95% CI, 88-93). After CIN treatment, the overall agreement was 87% (95% CI, 82-91) at Herlev and 88% (95% CI, 82-92) at Hvidovre. There were no significant differences in the sensitivity for >=CIN2 between the two tests [Herlev, 98% (95% CI, 89-100) for HC2 versus 94% (95% CI, 82-99) for cobas; Hvidovre, 97% (95% CI, 83-100) for HC2 versus 100% (95% CI, 88 100) for cobas]. The differences were also not significant for specificity. CONCLUSIONS: In women with the studied well-defined clinical indications for HPV testing, cobas and HC2 performed similarly in terms of the detection of HPV and >=CIN2. PMID- 26990234 TI - Regeneration of articular cartilage using adipose stem cells. AB - Articular cartilage (AC) has limited potential for self-regeneration and damage to AC eventually leads to the development and progression of osteoarthritis (OA). Cell implantation strategies have emerged as a new treatment modality to regenerate AC. Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. These advantages lower the cost of cell therapy by circumventing time-consuming procedure of culture expansion. ASCs have drawn attention as a potential source for cartilage regeneration since the feasibility of chondrogenesis from ASCs was first reported. After several groups reported inferior chondrogenesis from ASCs, numerous methods were devised to overcome the intrinsic properties. Most in vivo animal studies have reported good results using predifferentiated or undifferentiated, autologous or allogeneic ASCs to regenerate cartilage in osteochondral defects or surgically-induced OA. In this review, we summarize literature on the isolation and in vitro differentiation processes of ASCs, in vivo studies to regenerate AC in osteochondral defects and OA using ASCs, and clinical applications of ASCs. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1830-1844, 2016. PMID- 26990235 TI - Visible Raman excitation laser induced power and exposure dependent effects in red blood cells. AB - We present results of Raman spectroscopic studies carried out on optically trapped red blood cells with Raman excitation wavelength in Q-band region of the hemoglobin (Hb) absorption spectrum. The results obtained suggest that when exposed to the Raman excitation laser the RBCs get deoxygenated due to photo dissociation of oxygen from hemoglobin. For smaller exposure durations (5 s) the level of deoxygenation increases with an increase in power. However, for longer exposure durations the deoxygenated hemoglobin in the cells gets irreversibly oxidized to form a low spin ferric derivative of hemoglobin. The rate of oxidation depends upon the initial level of deoxygenation; higher the initial level of deoxygenation, higher is the rate of oxidation. However, the RBCs deoxygenated via oxygen deprivation (i.e. N2 purging) were found to be very stable against any laser induced effect. These observations suggests that in case of laser induced deoxygenation of RBCs the free oxygen generated by photo dissociation acts as the oxidizing agent and leads to oxidative damage of the RBCs. PMID- 26990236 TI - European Society of Endodontology position statement: Revitalization procedures. AB - This position statement represents a consensus of an expert committee convened by the European Society of Endodontology (ESE) on revitalization procedures. The statement is based on current clinical and scientific evidence as well as the expertise of the committee. The goal is to provide suitably trained dentists with a protocol including procedural details for the treatment of immature teeth with pulp necrosis as well as a patient consent form. Revitalization is a biologically based treatment as an alternative to apexification in properly selected cases. Previously published review articles provide more detailed background information and the basis for this position statement (Journal of Endodontics, 39, 2013, S30; Journal of Endodontics, 39, 2013, 319; Journal of Endodontics, 40, 2014, 1045; Dental Traumatology, 31, 2015, 267; International Endodontic Journal, 2015, doi: 10.1111/iej.12606). As controlled clinical trials are lacking and new evidence is still emerging, this position statement will be updated at appropriate intervals. This might lead to changes to the protocol provided here. PMID- 26990237 TI - Unintentional Pharmaceutical-Related Medication Errors Caused by Laypersons Reported to the Toxicological Information Centre in the Czech Republic. AB - The purpose of the article was to study unintentional pharmaceutical-related poisonings committed by laypersons that were reported to the Toxicological Information Centre in the Czech Republic. Identifying frequency, sources, reasons and consequences of the medication errors in laypersons could help to reduce the overall rate of medication errors. Records of medication error enquiries from 2013 to 2014 were extracted from the electronic database, and the following variables were reviewed: drug class, dosage form, dose, age of the subject, cause of the error, time interval from ingestion to the call, symptoms, prognosis at the time of the call and first aid recommended. Of the calls, 1354 met the inclusion criteria. Among them, central nervous system-affecting drugs (23.6%), respiratory drugs (18.5%) and alimentary drugs (16.2%) were the most common drug classes involved in the medication errors. The highest proportion of the patients was in the youngest age subgroup 0-5 year-old (46%). The reasons for the medication errors involved the leaflet misinterpretation and mistaken dose (53.6%), mixing up medications (19.2%), attempting to reduce pain with repeated doses (6.4%), erroneous routes of administration (2.2%), psychiatric/elderly patients (2.7%), others (9.0%) or unknown (6.9%). A high proportion of children among the patients may be due to the fact that children's dosages for many drugs vary by their weight, and more medications come in a variety of concentrations. Most overdoses could be prevented by safer labelling, proper cap closure systems for liquid products and medication reconciliation by both physicians and pharmacists. PMID- 26990239 TI - HLA-B*40:167, a novel allele, identified in a Chinese individual. AB - HLA-B*40:167 has one nucleotide change from HLA-B*40:06:01:01 at nucleotide 388 where 106D is changed to H. PMID- 26990238 TI - A qualitative study of experienced nurses' voluntary turnover: learning from their perspectives. AB - AIMS AND OBJECTIVES: The purpose of this research was to critically examine the factors that contribute to turnover of experienced nurses' including their decision to leave practice settings and seek alternate nursing employment. In this study, we explore experienced nurses' decision-making processes and examine the personal and environmental factors that influenced their decision to leave. BACKGROUND: Nursing turnover remains a pressing problem for healthcare delivery. Turnover contributes to increased recruitment and orientation cost, reduced quality patient care and the loss of mentorship for new nurses. DESIGN: A qualitative, interpretive descriptive approach was used to guide the study. METHODS: Interviews were conducted with 12 registered nurses, averaging 16 years in practice. Participants were equally represented from an array of acute care inpatient settings. The sample drew on perspectives from point-of-care nurses and nurses in leadership roles, primarily charge nurses and clinical nurse educators. RESULTS: Nurses' decisions to leave practice were influenced by several interrelated work environment and personal factors: higher patient acuity, increased workload demands, ineffective working relationships among nurses and with physicians, gaps in leadership support and negative impacts on nurses' health and well-being. Ineffective working relationships with other nurses and lack of leadership support led nurses to feel dissatisfied and ill equipped to perform their job. The impact of high stress was evident on the health and emotional well-being of nurses. CONCLUSIONS: It is vital that healthcare organisations learn to minimise turnover and retain the wealth of experienced nurses in acute care settings to maintain quality patient care and contain costs. RELEVANCE TO CLINICAL PRACTICE: This study highlights the need for healthcare leaders to re-examine how they promote collaborative practice, enhance supportive leadership behaviours, and reduce nurses' workplace stressors to retain the skills and knowledge of experienced nurses at the point-of-care. PMID- 26990240 TI - A successful case of deceased donor liver transplantation for a patient with intrahepatic arterioportal fistula. AB - Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension that is often difficult to treat with interventional radiology or surgery. Liver transplantation for IAPF is extremely rare. We report a case of bilateral diffuse IAPF with severe portal hypertension requiring deceased donor liver transplantation (DDLT). A 51-year-old woman with no past medical history was admitted to another hospital complaining of abdominal distension and marasmus. A computed tomography scan and digital subtraction angiography indicated a massive pleural effusion, ascites, and a very large IAPF. Several attempts of interventional embolization of the feeding artery failed to ameliorate arterioportal shunt flow. As ruptures of the esophageal varices became more frequent, hepatic encephalopathy worsened. After repeated, uncontrollable attacks of hepatic coma, the patient was referred to our facility for further treatment. Surgical approaches to IAPF other than liver transplantation were challenging because of diffuse collateralization; therefore, we placed the patient on the national waiting list for DDLT. Although her Model for End-Stage Liver Disease score was relatively low, she received a DDLT 2 months after the waiting period. The postoperative course was uneventful, and the patient was discharged 44 days after her transplant. Liver transplantation may be a valid treatment option for uncontrollable IAPF with severe portal hypertension. PMID- 26990241 TI - Employing Theories Far beyond Their Limits-The Case of the (Boguer-) Beer-Lambert Law. AB - For spectroscopists, the (Bouguer-)Beer-Lambert law is unquestionably an essential principle, since it is inseparably linked with one of the most important quantities in spectroscopy, the absorbance. In spite of its importance, a quantitative discussion of the legitimacy of relating the transmittance, the quantity that is usually measured, to the absorbance by assuming a logarithmic relation between both quantities cannot be found in literature. In this contribution, we quantitatively discuss, based on examples, the errors that can be introduced by disregarding the exact solution based on Maxwell's equations and show that these errors can easily exceed one order of magnitude. We also re derive the Beer-Lambert law, thereby providing guidance as how to convert transmittance into absorbance properly. PMID- 26990242 TI - Identification of pinostilbene as a major colonic metabolite of pterostilbene and its inhibitory effects on colon cancer cells. AB - SCOPE: Pterostilbene (PTE) is a resveratrol derivative mainly found in blueberries, and it has been shown to inhibit colon carcinogenesis in multiple animal models. To shed light on the mechanism of PTE in inhibiting colon carcinogenesis, we investigated the PTE metabolites in the mouse colon and in the human colon cancer cells. METHODS AND RESULTS: CD-1 mice were fed PTE-containing diet for 3 weeks, and colonic content and colonic mucosa were collected and subjected to LC-MS analysis. Pinostilbene (PIN) was identified as a major metabolite of PTE in the mouse colon. Importantly, the level of PIN was found to be approximately equivalent to that of PTE in the colonic mucosa. PIN significantly inhibited the growth of human colon cancer cells, i.e., HCT116 and HT29. These inhibitory effects were similar to those produced by PTE. Moreover, under physiologically relevant conditions, 20 and 40 MUM of PIN caused cell cycle arrest at S phase and induced apoptosis in colon cancer cells. These effects were associated with profound modulation of signaling proteins related with cell proliferation and programmed cell death. CONCLUSION: Our results demonstrated that PIN is a major metabolite of PTE in the colon of mice fed with PTE, and PIN may play important roles in the anti-colon cancer effects elicited by orally administered PTE. PMID- 26990243 TI - Clinical implications of mucosal remodeling from chronic rhinosinusitis. AB - BACKGROUND: Prognostic implications of mucosal remodeling in chronic rhinosinusitis (CRS) remain unclear. Remodeling of respiratory mucosa in asthma is associated with greater medication use and decreased function. This study investigates the implications of mucosal remodeling on long-term clinical outcomes in patients with CRS. METHODS: A case-control study of adult patients with CRS undergoing endoscopic sinus surgery (ESS) was performed. Mucosal remodeling was defined by squamous metaplasia, subepithelial fibrosis, and/or basement membrane thickening. The presence of remodeling changes were assessed relative to clinical and treatment outcomes at a minimum of 12 months postoperatively. Clinical outcomes were assessed at baseline and 12 months using a Nasal Symptom Score (NSS) and 22-item Sino-Nasal Outcome Test (SNOT-22). Treatment outcomes were assessed by oral corticosteroid usage (burst/continuous), topical corticosteroid irrigation frequency, and further surgical intervention. RESULTS: A total of 110 patients (48.73 +/- 14.75 years, 48.2% female) were assessed. Significant improvements where seen for the entire population, in both NSS (2.64 +/- 1.06 to 1.34 +/- 1.08, p < 0.001) and SNOT-22 (2.05 +/- 0.96 to 1.06 +/- 0.79, p < 0.001). Patients with remodeling (n = 88) were younger (47.2 +/- 14.8 vs 54.7 +/- 13.5 years, p = 0.03), but had similar symptom scores. Remodeling was seen in CRS with nasal polyposis (CRSwNP) (54.5%) and eosinophilic chronic rhinosinusitis (eCRS) (59.8%). Symptom improvement at 12 months was similar between remodeled and non-remodeled groups (NSS: Delta1.34 +/- 1.20 vs Delta1.12 +/- 1.31, p = 0.395; SNOT-22: Delta1.05 +/- 0.91 vs Delta0.73 +/- 0.95, p = 0.124); however, patients with remodeling had greater corticosteroid irrigation frequency (64.0% vs 31.6% daily use, Kendall's tau-b p = 0.004). CONCLUSION: Established mucosal remodeling predicts a greater reliance on topical therapies to reach similar clinical endpoints as those without remodeling. PMID- 26990244 TI - Single-Face/All-cis Arene Hydrogenation by a Supported Single-Site d(0) Organozirconium Catalyst. AB - The single-site supported organozirconium catalyst Cp*ZrBz2 /ZrS (Cp*=Me5 C5 , Bz=benzyl, ZrS=sulfated zirconia) catalyzes the single-face/all-cis hydrogenation of a large series of alkylated and fused arene derivatives to the corresponding all-cis-cyclohexanes. Kinetic/mechanistic and DFT analysis argue that stereoselection involves rapid, sequential H2 delivery to a single catalyst-bound arene face, versus any competing intramolecular arene pi-face interchange. PMID- 26990245 TI - Increased autophagy is required to protect periodontal ligament stem cells from apoptosis in inflammatory microenvironment. AB - OBJECTIVE: Autophagy, which provides a mechanism for turnover cellular organelles and proteins through a lysosome-dependent degradation pathway, has been related to the pathogenesis of inflammatory disorders and other diseases. Therefore, the aim of this research was to study the role of autophagy in periodontal ligament stem cells (PDLSCs) and provide a new strategy for treatment or prevention of periodontitis. METHODS: We used immunohistochemistry to detect the LC3 expression in periodontal ligament (PDL) tissues from patients with (n = 20) or without (n = 20) periodontitis. To further investigate the mechanism of autophagy, the PDLSCs were divided into three groups: H-PDLSCs, P-PDLSCs and I-PDLSCs. The level of autophagy in PDLSCs was evaluated by qRT-PCR and Western blot. LC3-positive points were assessed by immunofluorescence, and the autophagic vacuoles (AVs) were observed by transmission electron microscope. RESULTS: We found a higher level of autophagy in gene expression and autophagosome production of PDL tissues from periodontitis patients. Furthermore, there were higher protein levels of LC3, Beclin-1, Atg7 and Atg12 in P-PDLSCs and I-PDLSCs. We also detected LC3 positive points and AVs in P-PDLSCs and I-PDLSCs. The activation of autophagy may protect PDLSCs from apoptosis. CONCLUSION: The results indicate that the modulation of autophagy in P-PDLSCs may provide a novel therapeutic strategy to improve periodontal therapy. PMID- 26990246 TI - Simultaneous identification of host, ectoparasite and pathogen DNA via in solution capture. AB - Ectoparasites frequently vector pathogens from often unknown pathogen reservoirs to both human and animal populations. Simultaneous identification of the ectoparasite species, the wildlife host that provided their most recent blood meal(s), and their pathogen load would greatly facilitate the understanding of the complex transmission dynamics of vector-borne diseases. Currently, these identifications are principally performed using multiple polymerase chain reaction (PCR) assays. We developed an assay (EctoBaits) based on in-solution capture paired with high-throughput sequencing to simultaneously identify ectoparasites, host blood meals and pathogens. We validated our in-solution capture results using double-blind PCR assays, morphology and collection data. The EctoBaits assay effectively and efficiently identifies ectoparasites, blood meals, and pathogens in a single capture experiment, allowing for high-resolution taxonomic identification while preserving the DNA sample for future analyses. PMID- 26990247 TI - Syntheses, Charge Separation, and Inverted Bulk Heterojunction Solar Cell Application of Phenothiazine-Fullerene Dyads. AB - A series of phenothiazine-fulleropyrrolidine (PTZ-C60) dyads having fullerene either at the C-3 aromatic ring position or at the N-position of phenothiazine macrocycle were newly synthesized and characterized. Photoinduced electron transfer leading to PTZ(*+)-C60(*-) charge-separated species was established from studies involving femtosecond transient absorption spectroscopy. Because of the close proximity of the donor and acceptor entities, the C-3 ring substituted PTZ C60 dyads revealed faster charge separation and charge recombination processes than that observed in the dyad functionalized through the N-position. Next, inverted organic bulk heterojunction (BHJ) solar cells were constructed using the dyads in place of traditionally used [6,6]-phenyl-C61- butyric acid methyl ester (PCBM) and an additional electron donor material poly(3-hexylthiophene) (P3HT). The performance of the C-3 ring substituted PTZ-C60 dyad having a polyethylene glycol substituent produced a power conversion efficiency of 3.5% under inverted bulk heterojunction (BHJ) configuration. This was attributed to optimal BHJ morphology between the polymer and the dyad, which was further promoted by the efficient intramolecular charge separation and relatively slow charge recombination promoted by the dyad within the BHJ structure. The present finding demonstrate PTZ-C60 dyads as being good prospective materials for building organic photovoltaic devices. PMID- 26990249 TI - Glomus tumour of the kidney: a case report and review of the literature. PMID- 26990248 TI - Re-starting smoking in the postpartum period after receiving a smoking cessation intervention: a systematic review. AB - AIMS: In pregnant smoking cessation trial participants, to estimate (1) among women abstinent at the end of pregnancy, the proportion who re-start smoking at time-points afterwards (primary analysis) and (2) among all trial participants, the proportion smoking at the end of pregnancy and at selected time-points during the postpartum period (secondary analysis). METHODS: Trials identified from two Cochrane reviews plus searches of Medline and EMBASE. Twenty-seven trials were included. The included trials were randomized or quasi-randomized trials of within-pregnancy cessation interventions given to smokers who reported abstinence both at end of pregnancy and at one or more defined time-points after birth. Outcomes were validated biochemically and self-reported continuous abstinence from smoking and 7-day point prevalence abstinence. The primary random-effects meta-analysis used longitudinal data to estimate mean pooled proportions of re starting smoking; a secondary analysis used cross-sectional data to estimate the mean proportions smoking at different postpartum time-points. Subgroup analyses were performed on biochemically validated abstinence. RESULTS: The pooled mean proportion re-starting at 6 months postpartum was 43% [95% confidence interval (CI) = 16-72%, I(2) = 96.7%] (11 trials, 571 abstinent women). The pooled mean proportion smoking at the end of pregnancy was 87% (95% CI = 84-90%, I(2) = 93.2%) and 94% (95% CI = 92-96%, I(2) = 88%) at 6 months postpartum (23 trials, 9262 trial participants). Findings were similar when using biochemically validated abstinence. CONCLUSIONS: In clinical trials of smoking cessation interventions during pregnancy only 13% are abstinent at term. Of these, 43% re start by 6 months postpartum. PMID- 26990250 TI - Crafting Core/Graded Shell-Shell Quantum Dots with Suppressed Re-absorption and Tunable Stokes Shift as High Optical Gain Materials. AB - The key to utilizing quantum dots (QDs) as lasing media is to effectively reduce non-radiative processes, such as Auger recombination and surface trapping. A robust strategy to craft a set of CdSe/Cd(1-x)Zn(x)Se(1-y)S(y)/ZnS core/graded shell-shell QDs with suppressed re-absorption, reduced Auger recombination rate, and tunable Stokes shift is presented. In sharp contrast to conventional CdSe/ZnS QDs, which have a large energy level mismatch between CdSe and ZnS and thus show strong re-absorption and a constrained Stokes shift, the as-synthesized CdSe/Cd(1 x)Zn(x)Se(1-y)S(y)/ZnS QDs exhibited the suppressed re-absorption of CdSe core and tunable Stokes shift as a direct consequence of the delocalization of the electron wavefunction over the entire QD. Such Stokes shift-engineered QDs with suppressed re-absorption may represent an important class of building blocks for use in lasers, light emitting diodes, solar concentrators, and parity-time symmetry materials and devices. PMID- 26990252 TI - Shiga toxin of enterohaemorrhagic Escherichia coli directly injures developing human erythrocytes. AB - Haemolytic anaemia is one of the characteristics of life-threatening extraintestinal complications in humans during infection with enterohaemorrhagic Escherichia coli (EHEC). Shiga toxins (Stxs) of EHEC preferentially damage microvascular endothelial cells of the kidney and the brain, whereby occluded small blood vessels may elicit anaemia through mechanical erythrocyte disruption. Here we show for the first time that Stx2a, the major virulence factor of EHEC, is also capable of direct targeting developing human erythrocytes. We employed an ex vivo erythropoiesis model using mobilized CD34(+) haematopoietic stem/progenitor cells from human blood and monitored expression of Stx receptors and Stx2a-mediated cellular injury of developing erythrocytes. CD34(+) haematopoietic stem/progenitor cells were negative for Stx2a receptors and resistant towards the toxin. Expression of Stx2a-binding glycosphingolipids and toxin sensitivity was apparent immediately after initiation of erythropoietic differentiation, peaked for basophilic and polychromatic erythroblast stages and declined during maturation into orthochromatic erythroblasts and reticulocytes, which became highly refractory to Stx2a. The observed Stx-mediated toxicity towards erythroblasts during the course of erythropoiesis might contribute, although speculative at this stage of research, to the anaemia caused by Stx producing pathogens. PMID- 26990251 TI - Unusually long duration and delayed penetrance in a family with FTD and mutation in MAPT (V337M). AB - Mutations in the MAPT gene coding for the tau protein are one of the most common causes of familial frontotemporal dementia (FTD). In a previously described family with the V337M mutation in MAPT, we now report an affected woman who died at age 92 with a >40 year duration of symptoms, more than three times the mean disease duration in her family (13.8 years). Neuropathology showed the typical findings of a diffuse tauopathy. Conversely, her 67-year-old son with the same mutation remains asymptomatic more than 15 years beyond the mean age of onset in the family (51.5 years). These two cases demonstrate the marked variability in onset and duration of familial FTD and underscore the difficulties of discussing these issues with patients and families. The presumed genetic and environmental factors influencing these parameters remain largely unknown. (c) 2016 Wiley Periodicals, Inc. PMID- 26990253 TI - Prediction of spontaneous preterm birth in women with cervical insufficiency: Comprehensive analysis of multiple proteins in amniotic fluid. AB - AIM: The purpose of this study is to determine whether proinflammatory cytokines and matrix metalloproteinases (MMPs) in amniotic fluid (AF), alone or in combination with clinical risk factors, can predict spontaneous preterm delivery (SPTD) at < 34 weeks in women with cervical insufficiency. METHODS: This retrospective cohort study included 57 consecutive singleton pregnant women (17 28 gestational weeks) with cervical insufficiency who underwent amniocentesis. AF was assayed for five cytokines (interleukin [IL]-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1alpha, and MIP-1beta) and five MMPs (MMP-1, MMP-2, MMP-3, MMP-8, and MMP-9) using multiplex immunoassay kits. The primary outcome measure was SPTD at < 34 weeks. RESULTS: The AF concentrations of MMP-1, MMP-3, MMP-8, MMP-9, IL-6, IL-8, MIP-1alpha and MIP 1beta were significantly higher in women with SPTD at < 34 weeks. Women who had SPTD at < 34 weeks were younger, had significantly more advanced cervical dilatation at presentation and a higher rate of positive AF cultures. Using stepwise regression analysis, a combined prediction model was developed that included maternal age, cervical dilatation at presentation, AF MMP-1 and AF MMP-8 (area under the curve [AUC] 0.951). The AUC for this model was significantly greater than for any single protein alone in AF or for each of the clinical risk factors alone. CONCLUSION: A model combining proteins in AF and clinical factors can improve the accuracy of risk prediction for preterm birth and this combination is more accurate than each of the biomarkers alone in women with cervical insufficiency. PMID- 26990254 TI - Differential Use of the C-Type Lectins L-SIGN and DC-SIGN for Phlebovirus Endocytosis. AB - Bunyaviruses represent a growing threat to humans and livestock globally. The receptors, cellular factors and endocytic pathways used by these emerging pathogens to infect cells remain largely unidentified and poorly characterized. DC-SIGN is a C-type lectin highly expressed on dermal dendritic cells that has been found to act as an authentic entry receptor for many phleboviruses (Bunyaviridae), including Rift Valley fever virus (RVFV), Toscana virus (TOSV) and Uukuniemi virus (UUKV). We found that these phleboviruses can exploit another C-type lectin, L-SIGN, for infection. L-SIGN shares 77% sequence homology with DC SIGN and is expressed on liver sinusoidal endothelial cells. L-SIGN is required for UUKV binding but not for virus internalization. An endocytosis-defective mutant of L-SIGN was still able to mediate virus uptake and infection, indicating that L-SIGN acts as an attachment receptor for phleboviruses rather than an endocytic receptor. Our results point out a fundamental difference in the use of the C-type lectins L-SIGN and DC-SIGN by UUKV to enter cells, although both proteins are closely related in terms of molecular structure and biological function. This study sheds new light on the molecular mechanisms by which phleboviruses target the liver and also highlights the added complexity in virus receptor interactions beyond attachment. PMID- 26990256 TI - Prospective Randomized Split-Face Comparative Study Between Topical Botulinum Toxin A Surface Application and Local Injection for Crow's Feet. PMID- 26990255 TI - Correlation Between Appropriate Use Criteria and the Frequency of Subclinical Spread or Reconstruction With a Flap or Graft for Melanomas Treated With Mohs Surgery With Melanoma Antigen Recognized by T Cells 1 Immunostaining. AB - BACKGROUND: Published appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) for melanoma are based on consensus opinion. OBJECTIVE: To evaluate whether published AUC identify melanomas for which MMS may benefit patients by detecting subclinical spread or confirming clear microscopic margins before flap or graft reconstruction. MATERIALS AND METHODS: Retrospective cohort study of 591 melanomas in 556 patients evaluating the correlation between current AUC (anatomic location, recurrent status, and tumor stage) and subclinical spread or reconstruction with a flap or graft. RESULTS: Anatomic location on the head, neck, genitalia, hands, feet, or pretibial leg was associated with a significantly higher frequency of subclinical spread (odds ratio (OR) 1.89, p = .0280) and flap or graft reconstruction (OR 10.3, p = .0001). Compared with primary lesions, recurrent melanomas had a higher frequency of subclinical spread (OR 1.78, p = .0104) and reconstruction with a flap or graft (OR 1.67, p = .0217). The frequencies of subclinical spread and flap or graft reconstruction did not differ between in situ and invasive melanomas. CONCLUSION: Anatomic location and recurrent status are useful criteria to identify melanomas that may benefit from MMS. Tumor stage is not a useful criterion, as MMS has similar benefits for subsets of both invasive and in situ melanomas. PMID- 26990258 TI - Commentary on Hidden Transection of Follicular Unit Extraction in Donor Site. PMID- 26990257 TI - Avoiding Medical Errors in Cutaneous Site Identification: A Best Practices Review. AB - BACKGROUND: Although the field of dermatology has a relatively low incidence of medical errors, dermatologic surgery is a major area where medical errors occur. OBJECTIVE: The purpose of this article is to catalog the many cutaneous site identification techniques used by practitioners and determine which techniques are most evidence based. MATERIALS AND METHODS: A comprehensive literature review of cutaneous surgical site identification techniques and medical errors in dermatology. RESULTS: Wrong-site surgery often occurs because of an inability to identify the surgical site because of factors such as inadequate documentation from referring physicians, well-healed scars obscuring the biopsy site, and a patient's inability to visualize the surgical site. Practitioners use techniques such as photography, dermabrasion, written descriptions using anatomic landmarks, and site identification protocols for surgical site identification. CONCLUSION: Site identification remains a challenge for dermatologists and is a leading cause of medical errors in this field. Patients are often unreliable in their ability to identify biopsy sites; therefore, practitioners must take a proactive role to ensure that medical errors do not occur. This article provides a thorough description and evaluation of current site identification techniques used in dermatology with the aim to improve quality of care and reduce medical errors. PMID- 26990259 TI - Influence of everolimus on the pharmacokinetics of tacrolimus in Japanese renal transplant patients. AB - OBJECTIVES: To examine whether a trough concentration of everolimus in the therapeutic range of 3-5 ng/mL affects the pharmacokinetics of tacrolimus in renal transplant patients. METHODS: A total of 52 Japanese renal transplant patients receiving tacrolimus were enrolled in this study. In 28 of them, everolimus was co-administered on day 14 after surgery. Changes in the dose adjusted blood trough concentration of tacrolimus from day 14 to 28 after surgery were investigated. RESULTS: The dose-adjusted blood trough concentration of tacrolimus on day 28 was affected by CYP3A5*3/*3 and hemoglobin level (P < 0.001 and P = 0.007), but not by everolimus (P = 0.171). In addition, there was no change in the dose-adjusted blood trough concentration of tacrolimus in patients before or after everolimus coadministration (P = 0.165). On day 28, there was no correlation between the rate of change in the dose-adjusted blood trough concentration of tacrolimus and the blood trough concentration or area under the plasma concentration-time curve from 0 to 12 h for everolimus after initiation of combination therapy (r = 0.341, P = 0.076 and r = 0.234, P = 0.231). CONCLUSIONS: A pharmacokinetic interaction between tacrolimus and everolimus was not observed clinically in renal transplant patients. Safe and reliable immunosuppressive therapy in renal transplant patients might be achieved using a combination of tacrolimus and everolimus. PMID- 26990260 TI - Validation of the Alcohol Use Disorders Identification Test in university students: AUDIT and AUDIT-C. AB - The aim of this study was to determine the psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT and AUDIT-C) in order to detect problems related to the consumption of alcohol in the university population. The sample consisted of 1309 students.A Weekly Alcohol Consumption Diary was used as a gold standard; Cronbach's Alpha, the Kappa index, Spearman's correlation coefficient and exploratory factor analysis were applied for diagnostic reliability and validity, with ROC curves used to establish the different cut-off points. Binge Drinking (BD) episodes were found in 3.9% of men and 4.0% of women with otherwise low-risk drinking patterns. AUDIT identified 20.1% as high-risk drinkers and 6.4% as drinkers with physical-psychological problems and probable alcohol dependence.Cronbach's alpha of 0.75 demonstrates good internal consistency. The best cut-off points for high-risk drinking students were 8 for males and 6 for females. As for problem drinkers and probable ADS, 13 was the best cut-off point for both sexes. In relation to AUDIT-C, 5 and 4 were the best cut-off points for males and females with high-risk patterns, respectively. The criterion validity of AUDIT and AUDIT-C to detect binge drinking episodes was found to have a moderate K value. The results obtained show that AUDIT has good psychometric properties to detect early alcohol abuse disorders in university students; however, it is recommended that the cut-off point be reduced to 8 in men. AUDIT-C improves its predictive value by raising the cut-off point by one unit. Items 2 and 3 should be reviewed to increase its predictive value for BD. PMID- 26990261 TI - Cannabinoid hyperemesis syndrome. A report of six new cases and a summary of previous reports. AB - Cannabinoid hyperemesis syndrome (CHS) is a medical condition which was identified for the first time in 2004 and affects chronic users of cannabis. It is characterized by cyclic episodes of uncontrollable vomiting as well as compulsive bathing in hot water. The episodes have a duration of two to four days. The vomiting is recognizable by a lack of response to regular antiemetic treatment, and subsides only with cannabis abstinence, reappearing in periods of consumption of this substance. The etiology of this syndrome is unknown. Up until June 2014, 83 cases of CHS were published worldwide, four of them in Spain.The first patient of CHS at Mataro Hospital was diagnosed in 2012. Since then, five new cases have been identified. The average duration between the onset of acute CHS episodes and diagnosis is 6.1 years, similar to that observed in previously published cases, an average of 3.1 years. This "delay" of CHS diagnosis demonstrates a lack of awareness with respect to this medical condition in the healthcare profession.With the objective of providing information concerning CHS and facilitating its timely diagnosis, a series of six new cases of CHS diagnosed in Mataro Hospital is presented along with a summary of cases published between 2004 and June 2014. PMID- 26990262 TI - Association between personality traits and substance use in Spanish adolescents. AB - Substance use is considered one of the most frequent risk behaviors during adolescence. Personality factors are linked to consumption during adolescence. Although there are studies on personality and consumption among Spanish adolescents, some outcomes are contradictory, and more studies including larger samples and using validated measures are needed. The aim of this study is to analyze the relationship between different personality factors and substance use among Spanish adolescents. Participants were 1,455 students aged between 13-18 years. The adaptation of the 16PF-IPIP Personality Inventory was applied to assess Warmth, Stability, Gregariousness, Friendliness, Sensitivity, Trust, Openness to experience, Sociability, Perfectionism, and Calmness. Participants were asked about their different consumption substances during their lifetime. Results provide evidence for a relationship between personality factors and psychoactive substance use. There are different distributions of alcohol use regarding personality traits. Furthermore, personality factors have some influence on consumption of alcohol, cannabis, and cocaine.Trust and Calmness influence average alcohol, cannabis, and cocaine consumption, whereas Sociability had no statistically significant influence on any of the three substances. The results from this study are highly useful in the design of preventive programs, as they provide more evidence of the role of personality traits as a risk factor. PMID- 26990263 TI - Long term follow-up of a tobacco prevention and cessation program in cystic fibrosis patients. AB - This study evaluates the impact over time of a telephone-based intervention in tobacco cessation and prevention targeting patients with cystic fibrosis (CF) in the Mediterranean region of Murcia, Spain. We conducted an experimental prospective study with a cohort of CF patients using an integrative smoking cessation programme, between 2008 and 2013. The target population included family members and patients from the Regional CF unit. The study included an initial tobacco exposure questionnaire, measurement of lung function, urinary cotinine levels, anthropomorphic measures and the administered intervention at specific time intervals. Of the 88 patients tracked through follow-up, active smoking rates were reduced from 10.23% to 4.55% (p = 0.06). Environmental tobacco exposure was reduced in non-smoker patients from 62.03% to 36.90% (p < 0.01) during the five year follow-up. Significant reductions in the gradient of household tobacco smoke exposure were also observed with a decrease of 12.60%, from 31.65% (n = 25/79) to 19.05% (n = 16/84) in 2013 (p = <0.01). Cotinine was significantly correlated with both active and passive exposure (p<0.01) with a significant reduction of cotinine levels from 63.13 (28.58-97.69) to 20.56 (0.86 40.27) ng/ml (p<0.01). The intervention to significantly increase the likelihood of family quitting (smoke-free home) was 1.26 (1.05-1.54). Telephone based interventions for tobacco cessation and prevention is a useful tool when applied over time. Trained intervention professionals in this area are needed in the environmental health approach for the treatment of CF. PMID- 26990264 TI - Alcohol in Primary Care. Differential characteristics between alcohol-dependent patients who are receiving or not receiving treatment. AB - primary health care services for other reasons. The aim of the present study is to describe the differential characteristics of AD patients in primary care, distinguishing between those who receive treatment and those who do not, and their reasons for not seeking it. In a cross-sectional study patients were evaluated by their general practitioner (GP) and interviewed by a member of the research team. Sociodemographic, diagnostic and clinical data were collected. From 1,372 patients interviewed in Catalonia, 118 (8.6%) were diagnosed as AD. These patients showed a lower socioeconomic status (48.3% vs 33.3%, odds ratio 2.02), higher unemployment rates (32.2% vs 19.2 %, odds ratio 2.11), and greater psychological distress and disability. Patients with AD receiving treatment (16.9%), were older (44 vs 36 years of age), reported higher unemployment rates (66% vs 25.5%, odds ratio 6.32) and higher daily alcohol consumption (61.5 vs 23.7 grams), suggesting a more advanced disease. Patients with AD in general showed a higher degree of comorbidity compared to other patients, with patients in treatment showing the most elevated level. The main reasons given for not seeking treatment were shame, fear of giving up drinking and barriers to treatment. Taken together, the data suggest the need to implement earlier strategies for the detection and treatment of AD. PMID- 26990265 TI - Mortality due to acute adverse drug reactions in Galicia: 1997-2011. AB - The aim of this research is to study all people who died in the Autonomous Community of Galicia from acute death after drugconsumption (ADR) in which there was judicial intervention during the period from 1997 to 2011, according to inclusion and exclusion criteria established by the National Drug Plan for the entire national territory. Sociodemographic and clinical characteristics of deceased subjects were studied, in order to identify key risk factors and/or vulnerable populations.A total of 805 deaths were recorded. The distribution by provinces and municipalities corresponds to the areas of greatest population, incidence of consumption and proximity to the coast. The average age of these patients was 34.34 years, with a gradual increase over years. Most of them were male (91.2%) and single (47.7). 43.5% of the deceased habitually used the parenteral route of administration and 36.4% had positive HIV serology. The most frequently-detected substances corresponded to opiates (heroin: 61.3%, methadone: 35.6%), followed by cocaine (53.7%), although the most common pattern was that of poly-consumption. ADR mortality figures remain relatively stable throughout the study period. The predominant pattern is that of males, opiates and a long history of consumption. PMID- 26990266 TI - Psychotic-like Experiences and Substance Use in College Students. AB - Psychotic disorders, as well as psychotic-like experiences and substance use, have been found to be associated. The main goal of the present study was to analyse the relationship between psychoticlike experiences and substance use in college students. The simple comprised a total of 660 participants (M = 20.3 years, SD = 2.6). The results showed that 96% of the sample reported some delusional experience, while 20.3% reported at least one positive psychotic-like experience. Some substance use was reported by 41.1% of the sample, differing in terms of gender. Substance users reported more psychoticlike experiences than non users, especially in the positive dimension. Also, alcohol consumption predicted in most cases extreme scores on measures of delusional ideation and psychotic experiences. The association between these two variables showed a differentiated pattern, with a stronger relationship between substance use and cognitive perceptual psychotic-like experiences. To some extent, these findings support the dimensional models of the psychosis phenotype and contribute a better understanding of the links between psychoticlike experiences and substance use in young adults. Future studies should further explore the role of different risk factors for psychotic disorders and include models of the gene-environment interaction. PMID- 26990267 TI - Bipolar disorder and substance use disorders. Madrid study on the prevalence of dual disorders/pathology. AB - Given its prevalence and impact on public health, the comorbidity of bipolar and substance use disorders is one of the most relevant of dual diagnoses. The objective was to evaluate the characteristics of patients from community mental health and substance abuse centres in Madrid. The sample consisted of 837 outpatients from mental health and substance abuse centres. We used the Mini International Neuropsychiatric Interview (MINI) and Personality Disorder Questionnaire (PDQ4+) to evaluate axis I and II disorders. Of these patients, 174 had a lifetime bipolar disorder, 83 had bipolar disorder type I and 91 had type II. Most patients had dual pathology. Of the 208 participants from the mental health centres, 21 had bipolar disorder and 13 (61.9%) were considered dually diagnosed patients, while 33.2% of non-bipolar patients had a dual diagnoses (p = 0.03). Of the 629 participants from the substance abuse centres, 153 patients (24.3%) had a bipolar diagnosis. Bipolar dual patients had higher rates of alcohol and cocaine dependence than non-bipolar patients. Moreover, age at onset of alcohol use was earlier in bipolar duallydiagnosed patients than in other alcoholics. Bipolar dually-diagnosed patients had higher personality and anxiety disorder comorbidities and greater suicide risk. Thus, alcohol and cocaine are the drugs most associated with bipolar disorder. Given the nature of the study, the type of relationship between these disorders cannot be determined. PMID- 26990268 TI - Adolescents and Dual Diagnosis in a Psychiatric Emergency Service. AB - In recent years, both the prevalence of drug use and related child and adolescent psychiatric emergencies have risen sharply. There are few studies about the impact on child and adolescent emergency services. This study has a twofold aim. The first is to describe the prevalence of substance use disorders, mental disorders and dual diagnosis (substance use problems plus mental disorder) in adolescents in psychiatric emergency service. The second is to analyze clinical and healthcare differences between patients with dual diagnosis and patients with a mental disorder without substance use disorder.We retrospectively reviewed 4012 discharge forms for emergencies treated at the psychiatric emergency department during the period 2007-2009. We obtained a sample of 1795 visits. This sample was divided into two groups: the dual diagnosis group (n = 477) and the psychiatric disorder group (n = 1318).The dual diagnosis group accounted for 26.5% of psychiatric emergencies analyzed. Compared to the psychiatric disorder group,the dual diagnosis group had significantly more conduct disorders, social problems, involuntariness in the visit, less hospital admissions and less connection with the healthcare network.Adolescents with a dual diagnosis account for a high percentage of visits at child and adolescent psychiatric emergency services. This patient group requires specialized care both at emergency services and in specific units. Accordingly, these units should play a triple role when handling dual diagnosis: detection, brief treatment and referral to a specialised unit. PMID- 26990269 TI - Physical health, lifestyle beliefs and behaviors, and mental health of entering graduate health professional students: Evidence to support screening and early intervention. AB - BACKGROUND AND PURPOSE: Little is known about the physical health, lifestyle beliefs and behaviors, and mental health among first-year health professional graduate students. Therefore, the purpose of this study was to describe these attributes as well as to explore the relationships among them. METHODS: A descriptive correlational study was conducted on the baseline data from a wellness onboarding intervention study with 93 health sciences students from seven different colleges within a large public land grant university in the Midwest United States. FINDINGS: Nearly 40% of the sample was overweight/obese, and 19% of students had elevated total cholesterol levels. Only 44% met the recommended 30 min of exercise 5 days per week. Forty-one percent reported elevated depressive symptoms and 28% had elevated anxiety. Four students reported suicidal ideation. Inverse relationships existed among depression/anxiety and healthy lifestyle beliefs/behaviors. CONCLUSIONS: Students entering health professional schools are at high risk for depression, anxiety, and unhealthy behaviors, which could be averted through screening and early evidence-based interventions. IMPLICATIONS FOR PRACTICE: Assessing the physical health, lifestyle behaviors, and mental health of first-year health sciences professional students is important to identify health problems and modifiable at-risk behaviors so that early interventions can be implemented to improve outcomes. PMID- 26990270 TI - Perspectives on Comets, Comet-like Asteroids, and Their Predisposition to Provide an Environment That Is Friendly to Life. AB - In recent years, studies have shown that there are many similarities between comets and asteroids. In some cases, it cannot even be determined to which of these groups an object belongs. This is especially true for objects found beyond the main asteroid belt. Because of the lack of comet fragments, more progress has been made concerning the chemical composition of asteroids. In particular, the SMASSII classification establishes a link between the reflecting spectra and chemical composition of asteroids and meteorites. To find clues for the chemical structure of comets, the parameters of all known asteroids of the SMASSII classification were compared to those of comet groups like the Encke-type comets, the Jupiter-family comets, and the Halley-type comets, as well as comet-like objects like the damocloids and the centaurs. Fifty-six SMASSII objects similar to comets were found and are categorized as comet-like asteroids in this work. Aside from the chemistry, it is assumed that the available energy on these celestial bodies plays an important role concerning habitability. For the determination of the available energy, the effective temperature was calculated. Additionally, the size of these objects was considered in order to evaluate the possibility of a liquid water core, which provides an environment that is more likely to support processes necessary to create the building blocks of life. Further study of such objects could be notable for the period of the Late Heavy Bombardment and could therefore provide important implications for our understanding of the inner workings of the prebiotic evolution within the Solar System since the beginning. PMID- 26990271 TI - Anti-PD1-induced collagenous colitis in a melanoma patient. AB - Targeted immunotherapy has markedly improved the survival of melanoma patients. We report the case of a melanoma patient who developed a collagenous colitis under an anti-PD1 regimen. A 68-year-old woman was treated for a stage IV melanoma. An anti-PD1, pembrolizumab, was introduced after the failure of a first line therapy with an anti-CTLA4. At cycle 14, pembrolizumab was interrupted because of grade 3 diarrhea. Histologic analysis of colon mucosa showed a thickened apical subepithelial collagen layer with irregular collagen deposition of more than 25 um thickness. Budesonide 9 mg/day and cholestyramin 8 g/day were then introduced, leading to a decrease in the number of stools to grade 2. Because of the prognosis of the disease, the efficacy of pembrolizumab in this patient and the lack of other efficient treatments, pembrolizumab was restarted, with no worsening of the diarrhea after a follow-up of 8 weeks. In the era of immunotherapy, a new type of drug-induced colitis has emerged because of monoclonal antibodies targeting immune checkpoints such as CTLA-4 and PD1. Gastrointestinal tract immune-mediated adverse effects are now well described with ipilimumab. To the best of our knowledge, this is the first report of a collagenous colitis in a patient treated with pembrolizumab, thus suggesting a new mechanism of toxicity. Classically, collagenous colitis first-line treatment is based on discontinuation of the suspected treatment. However, there may be a strong benefit to maintaining an anti-PD1 regimen in our patients. In this case, symptomatic management associated with budesonide and cholestyramin enabled continuation of pembrolizumab. PMID- 26990272 TI - Skin self-examination and long-term melanoma survival. AB - To evaluate the effect of skin self-examination (SSE) on melanoma mortality, we estimated the survival for individuals performing SSE compared with those who did not. Participants were from a previously carried out case-control study, who were newly diagnosed melanoma cases in 1987-1989. A 20-year survival analysis was carried out using death (event) and other causes of death (competing). Cumulative incidence functions were evaluated using Gray's test and proportional subdistribution hazards regression models were fitted to study the effect of SSE and other covariates on melanoma survival. Forty-five percent of patients died, with 48.4% melanoma deaths. Individuals who did not perform SSE experienced a continuous increase in the risk of melanoma death trending toward significance for nearly 20 years after diagnosis, whereas melanoma deaths in skin self examiners plateaued before 10 years after diagnosis (P=0.32). Univariate analyses suggested a 25% lower risk of melanoma death for those who performed SSE [hazard ratio (HR)=0.75, 95% confidence interval (CI)=0.43-1.32, P=0.32]. After adjusting for competing risks, the multivariate risk estimate was above one (HR=1.12, 95% CI=0.61-2.06, P=0.71). Skin awareness (HR=0.46, 95% CI=0.28-0.75, P<=0.01) was associated independently with a decreased risk of melanoma death. Although we did not find a significant association between melanoma mortality and SSE when adjusting for competing mortality and other covariates, we extended previous findings that increased skin awareness and tumor thickness are strongly inversely related to survival. Research is needed to continue developing best practices for melanoma screening and to further explore the components of SSE and long-term melanoma survival. PMID- 26990273 TI - A Closed Chondromimetic Environment within Magnetic-Responsive Liquified Capsules Encapsulating Stem Cells and Collagen II/TGF-beta3 Microparticles. AB - TGF-beta3 is enzymatically immobilized by transglutaminase-2 action to poly(l lactic acid) microparticles coated with collagen II. Microparticles are then encapsulated with stem cells inside liquified spherical compartments enfolded with a permselective shell through layer-by-layer adsorption. Magnetic nanoparticles are electrostatically bound to the multilayered shell, conferring magnetic-response ability. The goal of this study is to engineer a closed environment inside which encapsulated stem cells would undergo a self-regulated chondrogenesis. To test this hypothesis, capsules are cultured in chondrogenic differentiation medium without TGF-beta3. Their biological outcome is compared with capsules encapsulating microparticles without TGF-beta3 immobilization and cultured in normal chondrogenic differentiation medium containing soluble TGF beta3. Glycosaminoglycans quantification demosntrates that similar chondrogenesis levels are achieved. Moreover, collagen fibrils resembling the native extracellular matrix of cartilage can be observed. Importantly, the genetic evaluation of characteristic cartilage markers confirms the successful chondrogenesis, while hypertrophic markers are downregulated. In summary, the engineered capsules are able to provide a suitable and stable chondrogenesis environment for stem cells without the need of TGF-beta3 supplementation. This kind of self-regulated capsules with softness, robustness, and magnetic responsive characteristics is expected to provide injectability and in situ fixation, which is of great advantage for minimal invasive strategies to regenerate cartilage. PMID- 26990274 TI - The Impact of Multilocus Variable-Number Tandem-Repeat Analysis on PulseNet Canada Escherichia coli O157:H7 Laboratory Surveillance and Outbreak Support, 2008-2012. AB - The lack of pattern diversity among pulsed-field gel electrophoresis (PFGE) profiles for Escherichia coli O157:H7 in Canada does not consistently provide optimal discrimination, and therefore, differentiating temporally and/or geographically associated sporadic cases from potential outbreak cases can at times impede investigations. To address this limitation, DNA sequence-based methods such as multilocus variable-number tandem-repeat analysis (MLVA) have been explored. To assess the performance of MLVA as a supplemental method to PFGE from the Canadian perspective, a retrospective analysis of all E. coli O157:H7 isolated in Canada from January 2008 to December 2012 (inclusive) was conducted. A total of 2285 E. coli O157:H7 isolates and 63 clusters of cases (by PFGE) were selected for the study. Based on the qualitative analysis, the addition of MLVA improved the categorization of cases for 60% of clusters and no change was observed for ~40% of clusters investigated. In such situations, MLVA serves to confirm PFGE results, but may not add further information per se. The findings of this study demonstrate that MLVA data, when used in combination with PFGE-based analyses, provide additional resolution to the detection of clusters lacking PFGE diversity as well as demonstrate good epidemiological concordance. In addition, MLVA is able to identify cluster-associated isolates with variant PFGE pattern combinations that may have been previously missed by PFGE alone. Optimal laboratory surveillance in Canada is achieved with the application of PFGE and MLVA in tandem for routine surveillance, cluster detection, and outbreak response. PMID- 26990275 TI - Regulations Restrict Practice of Conversion Therapy. PMID- 26990276 TI - Intra-Wound Injection of Platelet-Rich Plasma in Addition to Vacuum-Assisted Closure for Non-Healing Wounds in Patients with Diabetes Mellitus. PMID- 26990277 TI - Opioid-Induced Constipation Survey in Patients with Chronic Noncancer Pain. AB - Chronic pain patients relying on chronic opioid therapy are often challenged with opioid-induced constipation (OIC), a difficult condition to treat that has a significant psychosocial impact on those who are affected (Bruner et al., J Pain Res, 8, 2015, 289). Unlike other side effects of opioids, OIC does not resolve over time during chronic opioid use, and treatments used for functional constipation often fail to provide adequate symptom relief (Nelson and Camilleri, Therap Adv Gastroenterol, 8, 2015, 206). Estimates of the prevalence of OIC vary. It has been reported that 15% to 90% of opioid users are affected by OIC (Gaertner et al., J Clin Gastroenterol, 49, 2015, 9; Wan et al., Am Health Drug Benefits, 8, 2015, 93; Coyne et al., Clinicoecon Outcomes Res, 6, 2014, 269). In addition, a recent rise in opioid prescriptions by nonpain specialists has contributed to the increase in opioid-related side effects, such as OIC (Nelson and Camilleri, Therap Adv Gastroenterol, 8, 2015, 206; Tuteja et al., Neurogastroenterol Motil, 22, 2010, 424). We conducted a survey on OIC through PainPathways magazine in fall of 2014 and in spring of 2015. Survey results showed the prevalence of depression and the modification of opioid dosage were higher than previously thought. Additionally, we found that discussions with healthcare workers regarding OIC do not take place regularly. Our results re emphasize the need for a consensus on OIC-specific diagnostic criteria, evidence based treatment strategies, outcome metrics, and education about OIC for both prescribers and patients to improve clinical outcome as well as patient satisfaction. PMID- 26990278 TI - Production of succinic acid by metabolically engineered microorganisms. AB - Succinic acid (SA) has been recognized as one of the most important bio-based building block chemicals due to its numerous potential applications. For the economical bio-based production of SA, extensive research works have been performed on developing microbial strains by metabolic engineering as well as fermentation and downstream processes. Here we review metabolic engineering strategies applied for bio-based production of SA using representative microorganisms, including Saccharomyces cerevisiae, Pichia kudriavzevii, Escherichia coli, Mannheimia succiniciproducens, Basfia succiniciproducens, Actinobacillus succinogenes, and Corynebacterium glutamicum. In particular, strategies employed for developing engineered strains of these microorganisms leading to the best performance indices (titer, yield, and productivity) are showcased based on the published papers as well as patents. Those processes currently under commercialization are also analyzed and future perspectives are provided. PMID- 26990280 TI - Changes in the mandibular angle during adulthood in South Africans. AB - OBJECTIVES: The purpose of this study was to measure the mandibular angle as a reflection of the biomechanical forces acting on the mandible and relate it to aging and loss of teeth. METHODS: A total of 717 mandibles of adult individuals were selected from the Pretoria Bone Collection. These mandibles were allocated to dentition subgroups according to their pattern of tooth loss. The angle of the mandible was measured with a mandibulometer. The variation in the mandibular angle was statistically analyzed by age regressions and comparisons between adjusted means of dentition subgroups. RESULTS: Aging per se was not associated with a greater mandibular angle. With limited tooth loss, aging was associated with a smaller mandibular angle in females. Generally the mandibular angle increased with tooth loss and was accentuated when an even occlusion pattern was lost rather than with more extensive tooth loss. A more pronounced increase in mandibular angle with tooth loss was noted in females and individuals of European ancestry. CONCLUSIONS: Tooth loss and not aging is associated with an increase in the mandibular angle. Masculinity and being from African ancestry provided some protection against an increase in the mandibular angle with tooth loss. The accentuated increase in the mandibular angle when an even occlusion pattern was disturbed supports the notion that an uneven loss of teeth was indeed associated with inefficient mastication. The unexpected decrease in angle noted in females with aging but limited tooth loss may be indicative of constructive changes beyond puberty. Am. J. Hum. Biol. 28:681-686, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990279 TI - A pilot randomized controlled trial of telephone-based cognitive behavioural therapy for preoperative bariatric surgery patients. AB - BACKGROUND: Psychosocial interventions can improve eating behaviours and psychosocial functioning in bariatric surgery candidates. However, those that involve face-to-face sessions are problematic for individuals with severe obesity due to mobility issues and practical barriers. OBJECTIVE: To examine the efficacy of a pre-operative telephone-based cognitive behavioural therapy (Tele-CBT) intervention versus standard pre-operative care for improving eating psychopathology and psychosocial functioning. METHODS: Preoperative bariatric surgery patients (N = 47) were randomly assigned to receive standard preoperative care (n = 24) or 6 sessions of Tele-CBT (n = 23). RESULTS: Retention was 74.5% at post-intervention. Intent-to-treat analyses indicated that the Tele-CBT group reported significant improvements on the Binge Eating Scale (BES), t (22) = 2.81, p = .01, Emotional Eating Scale (EES), t (22) = 3.44, p = .002, and Patient Health Questionnaire-9 (PHQ-9), t (22) = 2.71, p = .01, whereas the standard care control group actually reported significant increases on the EES, t (23) = 4.86, p < .001, PHQ-9, t (23) = 2.75, p = .01, and General Anxiety Disorder-7 (GAD-7), t (23) = 2.93, p = .008 over the same time period. CONCLUSIONS: Tele-CBT holds promise as a brief intervention for improving eating psychopathology and depression in bariatric surgery candidates. PMID- 26990281 TI - Efficacy of denosumab in joint preservation for patients with giant cell tumour of the bone. AB - BACKGROUND: Giant cell tumour of the bone (GCTB) is an aggressive osteolytic primary tumour. GCTB is rich in osteoclast-like giant cells and contains mononuclear cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. The potential therapeutic effect of denosumab was investigated with special reference to its role in joint preservation. METHODS: In this prospective non-randomised study patients with GCTB received denosumab for 6-11 months preoperatively. Serial radiographs and biopsy and resection tumour specimens were used to monitor response to denosumab. RESULTS: All 20 patients experienced pain relief in the first month of treatment. All patients demonstrated a positive radiographic response with improved subchondral and cortical bone which allowed intralesional tumour resection and preservation of the joint and articular surface in 18 cases. Histological examination following denosumab revealed rarely detectable osteoclast-like giant cells. There was an obvious increase in osteoid matrix and woven bone which showed rare RANK staining amongst the mononuclear cells and only focal RANKL positivity. At median 30 months follow-up after resection, local tumour recurrence occurred in three patients. CONCLUSION: Denosumab provides favourable and consistent clinical, radiographic and pathologic responses which facilitates less aggressive surgical treatment, especially joint preservation. However, the local recurrence rate for GCTB following resection does not seem to be affected by denosumab and remains a concern. PMID- 26990282 TI - Effect of Structural Phase Transition on Charge-Carrier Lifetimes and Defects in CH3NH3SnI3 Perovskite. AB - Methylammonium tin triiodide (MASnI3) has been successfully employed in lead-free perovskite solar cells, but overall power-conversion efficiencies are still significantly lower than for lead-based perovskites. Here we present photoluminescence (PL) spectra and time-resolved PL from 8 to 295 K and find a marked improvement in carrier lifetime and a substantial reduction in PL line width below ~110 K, indicating that the cause of the hindered performance is activated at the orthorhombic to tetragonal phase transition. Our measurements therefore suggest that targeted structural change may be capable of tailoring the relative energy level alignment of defects (e.g., tin vacancies) to reduce the background dopant density and improve charge extraction. In addition, we observe for the first time an above-gap emission feature that may arise from higher-lying interband transitions, raising the prospect of excess energy harvesting. PMID- 26990283 TI - Family morph matters: factors determining survival and recruitment in a long lived polymorphic raptor. AB - From an evolutionary perspective, recruitment into the breeding population represents one of the most important life-history stages and ultimately determines the effective population size. In order to contribute to the next generation, offspring must survive to sexual maturity, secure a territory and find a mate. In this study, we explore factors influencing both offspring survival and their subsequent recruitment into the local breeding population in a long-lived urban raptor, the black sparrowhawk (Accipiter melanoleucus). Adult black sparrowhawks show discrete colour polymorphism (dark and light morphs), and in South Africa, morphs are distributed clinally with the highest proportion of dark morphs (c.75%) present in our study population on the Cape Peninsula. Parental morph was associated with both survival and recruitment. For survival, parental morph combination was important - with young produced by pairs of contrasting morphs having higher survival rates than young fledged from like pairs. The association between recruitment and morph was more complex; with an interaction between male morph and breeding time, whereby recruitment of offspring from dark morph fathers was more likely when fledging earlier in the season. The opposite relationship was found for light morph fathers, with their offspring more likely to be recruited if fledged later in the season. This interaction may be due to differential morph-specific hunting success of fathers (males contribute most food provisioning), linked to background matching and crypsis in different weather conditions. Dark morph males may hunt more successfully in rainier and cloudier conditions, which occur more frequently earlier in the breeding season, and light morph males may be more successful later on, when weather conditions become increasingly brighter and drier. Our results reveal a complex situation whereby the family morph combination influences survival, and the father morphs specifically recruitment, revealing morph-specific benefits dependent on the timing of breeding. These empirical data are among the first to support the idea that differential fitness consequence of morph combination may explain balanced polymorphism in a vertebrate population. PMID- 26990285 TI - A colorimetric and fluorescent dual probe for palladium in aqueous medium and live cell imaging. AB - A colorimetric and fluorescent dual probe for palladium species was rationally developed by combining the resorufin fluorophore with allyl chloroformate. The probe enables the visual detection of palladium based on its vivid color change from pale yellow to pink and its fluorescence off-on response to palladium in PBS solution. The detection limit was calculated to be as low as 2.1 nM. The live cell imaging results showed that this probe could be used as an effective fluorescent probe for detecting intracellular palladium species. All these results featured its promising application prospects in the palladium analytical field. PMID- 26990284 TI - New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases. AB - : Although reactive oxygen species (ROS) act as crucial factors in the onset and progression of a wide array of diseases, they are also involved in numerous signalling pathways related to cell metabolism, growth and survival. ROS are produced at various cellular sites, and it is generally agreed that mitochondria generate the largest amount, especially those in cardiomyocytes. However, the identification of the most relevant sites within mitochondria, the interaction among the various sources, and the events responsible for the increase in ROS formation under pathological conditions are still highly debated, and far from being clarified. Here, we review the information linking the adaptor protein p66Shc with cardiac injury induced by ischaemia and reperfusion (I/R), including the contribution of risk factors, such as metabolic syndrome and ageing. In response to several stimuli, p66Shc migrates into mitochondria where it catalyses electron transfer from cytochrome c to oxygen resulting in hydrogen peroxide formation. Deletion of p66Shc has been shown to reduce I/R injury as well as vascular abnormalities associated with diabetes and ageing. However, p66Shc induced ROS formation is also involved in insulin signalling and might contribute to self-endogenous defenses against mild I/R injury. In addition to its role in physiological and pathological conditions, we discuss compounds and conditions that can modulate the expression and activity of p66Shc. LINKED ARTICLES: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. PMID- 26990287 TI - Nanostructuring Mixed-Dimensional Perovskites: A Route Toward Tunable, Efficient Photovoltaics. AB - 2D perovskites is one of the proposed strategies to enhance the moisture resistance, since the larger organic cations can act as a natural barrier. Nevertheless, 2D perovskites hinder the charge transport in certain directions, reducing the solar cell power conversion efficiency. A nanostructured mixed dimensionality approach is presented to overcome the charge transport limitation, obtaining power conversion efficiencies over 9%. PMID- 26990288 TI - A Model for Developing a Coparenting Relationship After Protracted Litigation: The Case of Antonia, a 14-Year-Old Caught in the Crossfire. AB - Research has consistently documented long-term negative effects of high-conflict divorce on children's mental health. Court-issued custody and visitation judgments require parental collaboration, yet it is often challenging for parents to shift their interactions from acrimonious to cooperative, leaving children at increased risk for further exposure to conflict. Clinicians have developed strategies that help parents reduce conflict and increase coparenting skills after divorce. In this work, therapists integrate an empathic, active clinical stance and incorporate parenting education and skill building to help shift parents from a relationship marked by conflict to collaboration. A clinical case study provides an illustration of the steps involved in engaging a highly reactive and acrimonious mother and father in a Coparenting Treatment after prolonged litigation. It traces specific changes the parents implemented during 2 years of monthly sessions and the positive effects on the family system, including both the daughter's relationship to each parent and the parents' capacity to cooperate on her behalf. PMID- 26990286 TI - Extraintestinal manifestations of celiac disease: 33-mer gliadin binding to glutamate receptor GRINA as a new explanation. AB - We propose a biochemical mechanism for celiac disease and non-celiac gluten sensitivity that may rationalize many of the extradigestive disorders not explained by the current immunogenetic model. Our hypothesis is based on the homology between the 33-mer gliadin peptide and a component of the NMDA glutamate receptor ion channel - the human GRINA protein - using BLASTP software. Based on this homology the 33-mer may act as a natural antagonist interfering with the normal interactions of GRINA and its partners. The theory is supported by numerous independent data from the literature, and provides a mechanistic link with otherwise unrelated disorders, such as cleft lip and palate, thyroid dysfunction, restless legs syndrome, depression, ataxia, hearing loss, fibromyalgia, dermatitis herpetiformis, schizophrenia, toxoplasmosis, anemia, osteopenia, Fabry disease, Barret's adenocarcinoma, neuroblastoma, urinary incontinence, recurrent miscarriage, cardiac anomalies, reduced risk of breast cancer, stiff person syndrome, etc. The hypothesis also anticipates better animal models, and has the potential to open new avenues of research. PMID- 26990289 TI - Time-Resolved Broadband Cavity-Enhanced Absorption Spectroscopy behind Shock Waves. AB - A fast and sensitive broadband absorption technique for measurements of high temperature chemical kinetics and spectroscopy has been developed by applying broadband cavity-enhanced absorption spectroscopy (BBCEAS) in a shock tube. The developed method has effective absorption path lengths of 60-200 cm, or cavity enhancement factors of 12-40, over a wavelength range of 280-420 nm, and is capable of simultaneously recording absorption time profiles over an ~32 nm spectral bandpass in a single experiment with temporal and spectral resolutions of 5 MUs and 2 nm, respectively. The accuracy of the kinetic and spectroscopic measurements was examined by investigating high-temperature reactions and absorption spectra of formaldehyde behind reflected shock waves using 1,3,5 trioxane as a precursor. The rate constants obtained for the thermal decomposition reactions of 1,3,5-trioxane (to three formaldehyde molecules) and formaldehyde (to HCO + H) agreed well with the literature data. High-temperature absorption cross sections of formaldehyde between 280 and 410 nm have been determined at the post-reflected-shock temperatures of 955, 1265, and 1708 K. The results demonstrate the applicability of the BBCEAS technique to time- and wavelength-resolved sensitive absorption measurements at high temperatures. PMID- 26990291 TI - A business of some heat: molecular imaging of phosphodiesterase 5. PMID- 26990290 TI - Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib in RAS-mutant relapsed or refractory myeloid malignancies. AB - BACKGROUND: RAS/RAF/mitogen-activated protein kinase activation is common in myeloid malignancies. Trametinib, a mitogen-activated protein kinase kinase 1 (MEK1)/MEK2 inhibitor with activity against multiple myeloid cell lines at low nanomolar concentrations, was evaluated for safety and clinical activity in patients with relapsed/refractory leukemias. METHODS: This phase 1/2 study accrued patients with any relapsed/refractory leukemia in phase 1. In phase 2, this study accrued patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) with NRAS or KRAS mutations (cohort 1); patients with AML, MDS, or chronic myelomonocytic leukemia (CMML) with a RAS wild-type mutation or an unknown mutation status (cohort 2); and patients with CMML with an NRAS or KRAS mutation (cohorts 3). RESULTS: The most commonly reported treatment-related adverse events were diarrhea, rash, nausea, and increased alanine aminotransferase levels. The phase 2 recommended dose for Trametinib was 2 mg orally daily. The overall response rates were 20%, 3%, and 27% for cohorts 1, 2, and 3, respectively, and this indicated preferential activity among RAS-mutated myeloid malignancies. Repeated cycles of trametinib were well tolerated with manageable or reversible toxicities; these results were similar to those of other trametinib studies. CONCLUSIONS: The selective, single agent activity of trametinib against RAS-mutated myeloid malignancies validates its therapeutic potential. Combination strategies based on a better understanding of the hierarchical role of mutations and signaling in myeloid malignancies are likely to improve the response rate and duration. Cancer 2016;122:1871-9. (c) 2016 American Cancer Society. PMID- 26990292 TI - Sulforaphane Inhibits c-Myc-Mediated Prostate Cancer Stem-Like Traits. AB - Preventive and therapeutic efficiencies of dietary sulforaphane (SFN) against human prostate cancer have been demonstrated in vivo, but the underlying mechanism(s) by which this occurs is poorly understood. Here, we show that the prostate cancer stem cell (pCSC)-like traits, such as accelerated activity of aldehyde dehydrogenase 1 (ALDH1), enrichment of CD49f+ fraction, and sphere forming efficiency, are attenuated by SFN treatment. Interestingly, the expression of c-Myc, an oncogenic transcription factor that is frequently deregulated in prostate cancer cells, was markedly suppressed by SFN both in vitro and in vivo. This is biologically relevant, because the lessening of pCSC like phenotypes mediated by SFN was attenuated when c-Myc was overexpressed. Naturally occurring thio, sulfinyl, and sulfonyl analogs of SFN were also effective in causing suppression of c-Myc protein level. However, basal glycolysis, a basic metabolic pathway that can also be promoted by c-Myc overexpression, was not largely suppressed by SFN, implying that, in addition to c-Myc, there might be another SFN-sensitive cellular factor, which is not directly involved in basal glycolysis, but cooperates with c-Myc to sustain pCSC like phenotypes. Our study suggests that oncogenic c-Myc is a target of SFN to prevent and eliminate the onset of human prostate cancer. J. Cell. Biochem. 117: 2482-2495, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990293 TI - Impact of Superoxide Dismutase Mimetic AEOL 10150 on the Endothelin System of Fischer 344 Rats. AB - Endothelin-1 is a potent vasoconstrictor and mitogenic peptide involved in the regulation of vasomotor tone and maintenance of blood pressure. Oxidative stress activates the endothelin system, and is implicated in pulmonary and cardiovascular diseases including hypertension, congestive heart failure, and atherosclerosis. Superoxide dismutase mimetics designed with the aim of treating diseases that involve reactive oxygen species in their pathophysiology may exert a hypotensive effect, but effects on the endothelin system are unknown. Our objective was to determine the effect of the superoxide dismutase mimetic AEOL 10150 on the basal endothelin system in vivo. Male Fischer-344 rats were injected subcutaneously with 0, 2 or 5 mg/kg body weight of AEOL 10150 in saline. Plasma oxidative stress markers and endothelins (bigET-1, ET-1, ET-2, ET-3) as well as lung and heart endothelin/nitric oxide system gene expressions were measured using HPLC-Coularray, HPLC-Fluorescence and RT-PCR respectively. AEOL 10150 reduced (p<0.05) the circulating levels of isoprostane (-25%) and 3-nitrotyrosine (-50%) measured in plasma 2h and 24h after treatment, confirming delivery of a physiologically-relevant dose and the potent antioxidant activity of the drug. The reduction in markers of oxidative stress coincided with sustained 24h decrease (p<0.05) of plasma levels of ET-1 (-50%) and ET-3 (-10%). Expression of preproET-1 and endothelin converting enzyme-1 mRNA were not altered significantly in the lungs. However preproET-1 (not significant) and ECE-1 mRNA (p<0.05) were increased (10-25%) in the heart. Changes in the lungs included decrease (p<0.05) of mRNA for the ET-1 clearance receptor ETB and the vasoconstriction-signaling ETA receptor (-30%), and an early surge of inducible nitric oxide synthase expression followed by sustained decrease (-40% after 24 hours). The results indicate that interception of the endogenous physiological flux of reactive nitrogen species and reactive oxygen species in rats impacts the endothelin/nitric oxide system, supporting a homeostatic relationship between those systems. PMID- 26990295 TI - Urothelial cancer of the urinary bladder: can lessons learned be applied to the upper urinary tract? AB - Even though urothelial cancer may occur anywhere in the urinary tract, it is most commonly found in the urinary bladder. Due to its higher incidence, this disease is studied in the bladder much more frequently than in the upper urinary tract. The question that arises is, to what extent can concepts and treatment paradigms derived from lower tract disease be applied to urothelial carcinoma of the upper urinary tract? This review aims at providing an overview of established care concepts in urothelial carcinoma of the bladder and applicability of these findings to tumors of the upper urinary tract. PMID- 26990294 TI - Primary care-based screening for cardiovascular risk factors in patients with psoriasis. AB - BACKGROUND: Studies assessing cardiovascular disease (CVD) risk factors in patients with psoriasis have been limited by selection bias, inappropriate controls or a reliance on data collected for clinical reasons. OBJECTIVES: To investigate whether screening for CVD risk factors in patients with psoriasis in primary care augments the known prevalence of CVD risk factors in a cross sectional study. METHODS: Patients listed as having psoriasis in primary care were recruited, screened and risk assessed by QRISK2. RESULTS: In total, 287 patients attended (mean age 53 years, 57% women, 94% white British, 22% severe disease, 33% self-reported psoriatic arthritis). The proportion with known and screen-detected (previously unknown) risk factors was as follows: hypertension 35% known and 13% screen-detected; hypercholesterolaemia 32% and 37%; diabetes 6.6% and 3.1% and chronic kidney disease 1.1% and 4.5%. At least one screen detected risk factor was found in 48% and two or more risk factors were found in 21% of patients. One in three patients (37%) not previously known to be at high risk were found to have a high (> 10%) 10-year CVD risk. Among the participants receiving treatment for known CVD risk factors, nearly half had suboptimal levels for blood pressure (46%) and cholesterol (46%). CONCLUSIONS: Cardiovascular risk factor screening of primary care-based adults with psoriasis identified a high proportion of patients (i) at high CVD risk, (ii) with screen-detected risk factors and (iii) with suboptimally managed known risk factors. These findings need to be considered alongside reports that detected limited responses of clinicians to identified risk factors before universal CVD screening can be recommended. PMID- 26990296 TI - Changes in the expression of IL-6-Mediated MicroRNAs in the dorsal root ganglion under neuropathic pain in mice. AB - A multiplex analysis for profiling the expression of candidate microRNAs (miRNAs), which are small noncoding RNAs that function as key post transcriptional regulators, may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we performed a miRNA array analysis using tissues of the dorsal root ganglion (DRG), a primary site for pain processing, obtained from mice with partial sciatic nerve ligation. Among 1135 total miRNAs, 26 miRNAs showed up-regulation (more than 2-fold change) and only 4 miRNAs showed down-regulation (less than 0.5-fold change) in the DRG of nerve ligated mice. In a RT-qPCR assay, the levels of miR-21, miR-431, and miR-511-3p were significantly increased on the ipsilateral side of the DRG from 3 to 7 days after sciatic nerve ligation. These elevations were almost absent in IL-6 knockout mice. Furthermore, the expression level of miR-21, but not those of miR 431 or miR511-3p, was significantly increased in exosomes extracted from blood of nerve-ligated mice. These findings suggest that the increased expression of IL-6 regulated miR-21, miR-431, and miR-511-3p in the DRG and increased exosomal miR 21 extracted from blood after sciatic nerve ligation may play at least a partial role in neuropathic pain. Synapse 70:317-324, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990298 TI - A Feasibility Study with Image-Based Rendered Virtual Reality in Patients with Mild Cognitive Impairment and Dementia. AB - Virtual Reality (VR) has emerged as a promising tool in many domains of therapy and rehabilitation, and has recently attracted the attention of researchers and clinicians working with elderly people with MCI, Alzheimer's disease and related disorders. Here we present a study testing the feasibility of using highly realistic image-based rendered VR with patients with MCI and dementia. We designed an attentional task to train selective and sustained attention, and we tested a VR and a paper version of this task in a single-session within-subjects design. Results showed that participants with MCI and dementia reported to be highly satisfied and interested in the task, and they reported high feelings of security, low discomfort, anxiety and fatigue. In addition, participants reported a preference for the VR condition compared to the paper condition, even if the task was more difficult. Interestingly, apathetic participants showed a preference for the VR condition stronger than that of non-apathetic participants. These findings suggest that VR-based training can be considered as an interesting tool to improve adherence to cognitive training in elderly people with cognitive impairment. PMID- 26990297 TI - Genomic Characterization of Phenylalanine Ammonia Lyase Gene in Buckwheat. AB - Phenylalanine Ammonia Lyase (PAL) gene which plays a key role in bio-synthesis of medicinally important compounds, Rutin/quercetin was sequence characterized for its efficient genomics application. These compounds possessing anti-diabetic and anti-cancer properties and are predominantly produced by Fagopyrum spp. In the present study, PAL gene was sequenced from three Fagopyrum spp. (F. tataricum, F. esculentum and F. dibotrys) and showed the presence of three SNPs and four insertion/deletions at intra and inter specific level. Among them, the potential SNP (position 949th bp G>C) with Parsimony Informative Site was selected and successfully utilised to individuate the zygosity/allelic variation of 16 F. tataricum varieties. Insertion mutations were identified in coding region, which resulted the change of a stretch of 39 amino acids on the putative protein. Our Study revealed that autogamous species (F. tataricum) has lower frequency of observed SNPs as compared to allogamous species (F. dibotrys and F. esculentum). The identified SNPs in F. tataricum didn't result to amino acid change, while in other two species it caused both conservative and non-conservative variations. Consistent pattern of SNPs across the species revealed their phylogenetic importance. We found two groups of F. tataricum and one of them was closely related with F. dibotrys. Sequence characterization information of PAL gene reported in present investigation can be utilized in genetic improvement of buckwheat in reference to its medicinal value. PMID- 26990299 TI - Xpert(r)MTB/RIF for the Diagnosis of Tuberculosis in a Remote Arctic Setting: Impact on Cost and Time to Treatment Initiation. AB - BACKGROUND: Tuberculosis (TB) remains a significant health problem in the Canadian Arctic. Substantial health system delays in TB diagnosis can occur, in part due to the lack of capacity for onsite microbiologic testing. A study recently evaluated the yield and impact of a rapid automated PCR test (Xpert(r)MTB/RIF) for the diagnosis of TB in Iqaluit (Nunavut). We conducted an economic analysis to evaluate the expected cost relative to the expected reduction in time to treatment initiation, with the addition of Xpert(r)MTB/RIF to the current diagnostic and treatment algorithms used in this setting. METHODS: A decision analysis model compared current microbiologic testing to a scenario where Xpert(r)MTB/RIF was added to the current diagnostic algorithm for active TB, and incorporated costs and clinical endpoints from the Iqaluit study. Several sensitivity analyses that considered alternative use were also considered. We estimated days to TB diagnosis and treatment initiation, health system costs, and the incremental cost per treatment day gained for each individual evaluated for possible TB. RESULTS: With the addition of Xpert(r)MTB/RIF, costs increased while days to TB treatment initiation were reduced. The incremental cost per treatment day gained (per individual investigated for TB) was $164 (95% uncertainty range $85, $452). In a sensitivity analysis that considered hospital discharge after a single negative Xpert(r)MTB/RIF, the Xpert(r)MTB/RIF scenario was cost saving. INTERPRETATION: Adding Xpert(r)MTB/RIF to the current diagnostic algorithm for TB in Nunavut appears to reduce time to diagnosis and treatment at reasonable cost. It may be especially well suited to overcome some of the other logistical barriers that are unique to this and other remote communities. PMID- 26990300 TI - Joint Analysis of Multiple Traits in Rare Variant Association Studies. AB - The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, the majority of existing methods for the joint analysis of multiple traits test association between one common variant and multiple traits. However, the variant-by-variant methods for common variant association studies may not be optimal for rare variant association studies due to the allelic heterogeneity as well as the extreme rarity of individual variants. Current statistical methods for rare variant association studies are for one single trait only. In this paper, we propose an adaptive weighting reverse regression (AWRR) method to test association between multiple traits and rare variants in a genomic region. AWRR is robust to the directions of effects of causal variants and is also robust to the directions of association of traits. Using extensive simulation studies, we compare the performance of AWRR with canonical correlation analysis (CCA), Single TOW, and the weighted sum reverse regression (WSRR). Our results show that, in all of the simulation scenarios, AWRR is consistently more powerful than CCA. In most scenarios, AWRR is more powerful than Single-TOW and WSRR. PMID- 26990301 TI - Employment Situation of Parents of Long-Term Childhood Cancer Survivors. AB - BACKGROUND: Taking care of children diagnosed with cancer affects parents' professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment. METHODS: As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5-15 years, who survived >=5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with >=1 child aged 5 15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry. RESULTS: We included 394 parent-couples of survivors and 3'341 control parents (1'731 mothers; 1'610 fathers). Mothers of survivors were more often not employed (29% versus 22%; ptrend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; ptrend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14-5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71-7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13-0.73) and >2 children (OR = 0.48, CI:0.30-0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04 0.36). CONCLUSION: Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation. PMID- 26990303 TI - Ultrasound-assisted temperature-controlled ionic liquid emulsification microextraction coupled with capillary electrophoresis for the determination of parabens in personal care products. AB - We developed a CE and ultrasound-assisted temperature-controlled ionic liquid emulsification microextraction method for the determination of four parabens (methyl paraben, ethyl paraben, propyl paraben, and butyl paraben) in personal care products including mouthwash and toning lotion. In the proposed extraction procedure, ionic liquid (IL, 1-octyl-3-methylimidazolium hexafluorophosphate) was used as extraction solvent, moreover, no disperser solvent was needed. Parameters affecting the extraction efficiency including volume of IL, heating temperature, ultrasonic time, extraction time, sample pH, ionic strength, and centrifugation time were optimized. Under the optimized conditions, the method was found to be linear over the range of 3-500 ng/mL with coefficient of determination (R(2) ) in the range of 0.9990-0.9998. The LODs and LOQs for the four parabens were 0.45 0.72 ng/mL and 1.50-2.40 ng/mL, respectively. Intraday and interday precisions (RSDs, n = 5) were in the range of 5.4-6.8% and 7.0-8.7%, respectively. The recoveries of parabens at different spiked levels ranged from 71.9 to 119.2% with RSDs less than 9.5%. PMID- 26990302 TI - Stromal Integrin alpha11beta1 Affects RM11 Prostate and 4T1 Breast Xenograft Tumors Differently. AB - PURPOSE: It has been implied that the collagen binding integrin alpha11beta1 plays a role in carcinogenesis. As still relatively little is known about how the stromal integrin alpha11beta1 affects different aspects of tumor development, we wanted to examine the direct effects on primary tumor growth, fibrosis, tumor interstitial fluid pressure (PIF) and metastasis in murine 4T1 mammary and RM11 prostate tumors, using an in vivo SCID integrin alpha11-deficient mouse model. METHODS: Tumor growth was measured using a caliper, PIF by the wick-in-needle technique, activated fibroblasts by alpha-SMA immunofluorescence staining and fibrosis by transmission electron microscopy and picrosirius-red staining. Metastases were evaluated using hematoxylin and eosin stained sections. RESULTS: RM11 tumor growth was significantly reduced in the SCID integrin alpha11 deficient (alpha11-KO) compared to in SCID integrin alpha11 wild type (WT) mice, whereas there was no similar effect in the 4T1 tumor model. The 4T1 model demonstrated an alteration in collagen fibril diameter in the integrin alpha11-KO mice compared to WT, which was not found in the RM11 model. There were no significant differences in the amount of activated fibroblasts, total collagen content, collagen organization or PIF in the tumors in integrin alpha11-deficient mice compared to WT mice. There was also no difference in lung metastases between the two groups. CONCLUSION: Deficiency of stromal integrin alpha11beta1 showed different effects on tumor growth and collagen fibril diameter depending on tumor type, but no effect on tumor PIF or development of lung metastasis. PMID- 26990304 TI - Does Routine Midazolam Administration Prior to Nasogastric Tube Insertion in the Emergency Department Decrease Patients' Pain? (A Pilot Study). AB - OBJECTIVES: Patients report pain and discomfort with nasogastric tube (NGT) intubation. We tested the hypothesis that premedication with midazolam alleviates pain during NGT placement in the emergency department (ED) by > 13 on a 100-mm visual analog scale (VAS). METHODS: We performed a double-blind randomized controlled pilot study, assigning ED patients requiring NGT placement to midazolam or placebo. All patients received intranasal cophenylcaine; additionally, they received an intravenous (IV) dose of the study drug, either 2 mg of IV midazolam or saline control. Nurses placed NGTs while observed by research staff, who then interviewed subjects to determine the primary outcome of pain using a VAS. Additional data collected from patients and their nurses included discomfort during the procedure, difficulty of tube insertion, and complications. RESULTS: We enrolled 23 eligible patients and obtained complete data in all: 10 midazolam and 13 controls. We found a significant reduction in mean pain VAS score of -31 (95% confidence interval = -53 to -9 mm) with 2 mg of midazolam (mean +/- SD = 52 +/- 30 mm), compared to placebo (mean +/- SD = 21 +/- 18 mm), more than double the effect size considered clinically relevant. Treatment did not impact ease of placement and there were no serious adverse effects. CONCLUSIONS: Premedication with 2 mg of IV midazolam reduces pain of NGT insertion in ED patients without the need for full procedural sedation. PMID- 26990305 TI - Nitrate Medications, Fractures, and Change in Bone Mineral Density in Postmenopausal Women: Results from the Women's Health Initiative. AB - Nitrate medications may increase bone mineral density (BMD), although information on fracture outcomes is sparse. We examined the association of nitrate medications with fractures (hip, wrist/arm, and total fractures) and changes in BMD (hip, spine, and whole body) in the Women's Health Initiative (WHI) Clinical Trials and Observational Study. A total of 139,211 postmenopausal women 50 to 79 years old without history of hip fracture were included in this prospective study. Medication use was ascertained directly from drug containers at baseline during in-person interviews in 1993 to 1998. Exposure measures included any use (use/non-use), type of nitrate (as-needed, maintenance) and duration of use (<=5 years, >5 years). We used separate multivariable Cox proportional hazard models to analyze associations between each exposure and fracture outcome, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariable linear regression models were used to examine 3-year and 6-year changes in BMD. At baseline, 1.2% (n = 1647) women were using a nitrate. During the mean +/- SD follow-up of 7.7 +/- 1.5 years through 2005, women experienced 1582 hip fractures, 5156 wrist or arm fractures, and 22, 589 total fractures. After adjustment for confounders, nitrate use was not statistically associated with risk for hip (HR, 0.81; 95% CI, 0.56 to 1.18), wrist/arm (HR, 0.95; 95% CI, 0.74 to 1.23), or total fractures (HR, 0.96; 95% CI, 0.85 to 1.08). As-needed nitrate use, but not maintenance therapy, was associated with a lower risk of total fractures (HR, 0.77; 95% CI, 0.62 to 0.95) and wrist/arm fractures (HR, 0.57; 95% CI, 0.34 to 0.98). Nitrate use was not associated with 3-year or 6-year changes in BMD at any site. We conclude that any nitrate use was not significantly associated with lower risk of fractures or higher BMD; however, as needed nitrate use was associated with lower risks of total and wrist/arm fractures. (c) 2016 American Society for Bone and Mineral Research. PMID- 26990306 TI - Increasing social welfare by taxing pesticide externalities in the Indian cotton sector. AB - BACKGROUND: Pesticide use in the Indian cotton industry has decreased with the introduction of Bt cotton, but rates are still high in comparison with other countries. The adoption of alternative strategies, such as integrated pest management, has been slow, even though benefits are potentially high, more so if the full costs of the external effects of the technologies are taken into account. In order to estimate true societal benefits of different strategies, we compare their external costs and economic performance under external cost taxation, using a state-of-the-art partial equilibrium model of the Indian agricultural sector. RESULTS: Pesticide externalities lower social welfare in the Indian cotton sector by $US 400-2200 million, depending on the technologies employed. A full internalisation reduces producer revenues by $US 100 ha-1 if only Bt cotton is used, and by $US 30 ha-1 if IPM is another option. Consumers do not start to lose surplus until 20-70% are internalised, and losses are smaller if all technologies are available. CONCLUSION: External pesticide costs can be internalised partially without substantially affecting consumer surplus while still increasing social welfare, but producers need to have access to and the knowledge to employ all available cotton production technologies to minimise losses. (c) 2016 Society of Chemical Industry. PMID- 26990307 TI - Comparison of failure rates of crossing side branch with pressure vs. coronary guidewire: a meta-analysis. AB - OBJECTIVES: The aim of this study was to compare the failure rates of crossing side branch (SB) with pressure guidewire vs. coronary guidewire after main vessel (MV) stenting in coronary bifurcation lesions (CBL). BACKGROUND: Percutaneous coronary intervention of CBL is technically difficult. The European Bifurcation Club recommends performing either fractional flow reserve (FFR) estimation of the SB or final kissing balloon inflation (FKBI) after the MV stenting when a significant SB ostial stenosis is present. Even though FFR is recommended in CBL, there is concern about SB crossing with pressure guidewire among interventionists. MATERIALS AND METHODS: We undertook a comprehensive literature search to identify all relevant studies reporting the failure rates of SB crossing after MV stenting with either pressure or coronary guidewire. A random effects model was used to compare the failure rates between the two approaches. RESULTS: Our search identified six studies that reported failure rates of SB crossing with a pressure guidewire (n = 648) and 11 studies that reported failure rates of SB crossing with a coronary guide-wire (n = 2601). Estimated pooled failure rate was 3.9% (95% CI: 1.5% to 9.6%) for inability to cross SB with pressure guidewire. Estimated pooled failure rate of SB crossing with coronary guidewire was 3.1% (95% CI: 1.5% to 6.2%). There was no significant difference between the failure rates in the two groups (P = 0.70). CONCLUSION: The failure rates of SB crossing after MV stenting are low with both pressure and coronary guidewire procedures, with no significant difference between the two approaches. PMID- 26990308 TI - Biphasic increase in scratching behaviour induced by topical application of Dermatophagoides farinae extract in NC/Nga mice. AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching and eczematous lesion. In this study, we applied an ointment containing Dermatophagoides farinae body (Dfb) extract repeatedly on the dorsal skin of NC/Nga mice with barrier disruption to investigate the characteristics of this murine model of human AD. Following repeated topical application of Dfb ointment twice weekly for 2 weeks, the dermatitis score increased gradually, accompanied by an elevation of total immunoglobulin E level in plasma. Topical application of Dfb ointment also caused epidermal hyperplasia and accumulation of inflammatory cells in the lesional skin and increased expression of T-helper (Th) 1/Th2/Th17 cytokines in axillary lymph node cells. Furthermore, increased sprouting of intraepidermal nerve fibres was observed with an increase in the content of nerve growth factor and decrease in that of semaphorin 3A in the lesional skin. These findings suggest that the characteristics in this model were similar to those observed in patients with AD. Interestingly, it was observed for the first time that scratching behaviour increased in a biphasic fashion by topical application of Dfb ointment in addition to an increase in spontaneous scratching behaviour in this model. It is also suggested that further clarifying the underlying mechanisms of scratching behaviour in this model leads not only to elucidating the pathogenesis of AD but also to discovering novel therapeutic drugs for AD. PMID- 26990310 TI - Chromosomes and clinical anatomy. AB - Chromosome abnormalities may cast light on the nature of mechanisms whereby normal anatomy evolves, and abnormal anatomy arises. Correlating genotype to phenotype is an exercise in which the geneticist and the anatomist can collaborate. The increasing power of the new genetic methodologies is enabling an increasing precision in the delineation of chromosome imbalances, even to the nucleotide level; but the classical skills of careful observation and recording remain as crucial as they always have been. Clin. Anat. 29:540-546, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990311 TI - Uranium Immobilization and Nanofilm Formation on Magnesium-Rich Minerals. AB - Polarization-dependent grazing incidence X-ray absorption spectroscopy (XAS) measurements were completed on oriented single crystals of magnesite [MgCO3] and brucite [Mg(OH)2] reacted with aqueous uranyl chloride above and below the solubility boundaries of schoepite (500, 50, and 5 ppm) at pH 8.3 and at ambient (PCO2 = 10(-3.5)) or reduced partial pressures of carbon dioxide (PCO2 = 10( 4.5)). X-ray absorption near edge structure (XANES) spectra show a striking polarization dependence (chi = 0 degrees and 90 degrees relative to the polarization plane of the incident beam) and consistently demonstrated that the uranyl molecule was preferentially oriented with its Oaxial?U(VI)?Oaxial linkage at high angles (60-80 degrees ) to both magnesite (1014) and brucite (0001). Extended X-ray absorption fine structure (EXAFS) analysis shows that the "effective" number of U(VI) axial oxygens is the most strongly affected fitting parameter as a function of polarization. Furthermore, axial tilt in the surface thin films (thickness ~ 21 A) is correlated with surface roughness [sigma]. Our results show that hydrated uranyl(-carbonate) complexes polymerize on all of our experimental surfaces and that this process is controlled by surface hydroxylation. These results provide new insights into the bonding configuration expected for uranyl complexes on the environmentally significant carbonate and hydroxide mineral surfaces. PMID- 26990309 TI - Vertebrate Claudin/PMP22/EMP22/MP20 family protein TMEM47 regulates epithelial cell junction maturation and morphogenesis. AB - BACKGROUND: TMEM47 is the vertebrate orthologue of C. elegans VAB-9, a tetraspan adherens junction protein in the PMP22/EMP/Claudin family of proteins. VAB-9 regulates cell morphology and adhesion in C. elegans and TMEM47 is expressed during kidney development and regulates the activity of Fyn. The conserved functions of VAB-9 and TMEM47 are not well understood. RESULTS: expression of TMEM47 in C. elegans functionally rescues vab-9 mutations. Unlike Claudins, expression of TMEM47 in L fibroblasts does not generate tight junction strands; instead, membrane localization requires E-cadherin expression. Temporally, TMEM47 localizes at cell junctions first with E-cadherin before ZO-1 colocalization and in polarized epithelia, TMEM47 colocalizes with adherens junction proteins. By immunoprecipitation, TMEM47 associates with classical adherens junction proteins, but also with tight junction proteins Par6B and aPKClambda. Over-expression of TMEM47 in MDCK cells decreases apical surface area, increases activated myosin light chain at cell-cell contacts, disrupts cell polarity and morphology, delays cell junction reassembly following calcium switch, and selectively interferes with tight junction assembly. Reduced TMEM47 expression results in opposite phenotypes. CONCLUSIONS: TMEM47 regulates the localization of a subset of tight junction proteins, associated actomyosin structures, cell morphology, and participates in developmental transitions from adherens to tight junctions. Developmental Dynamics 245:653-666, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990314 TI - Who can be more ignorant than an editor? PMID- 26990312 TI - Potentially Avoidable Hospitalizations among People at Different Activity of Daily Living Limitation Stages. AB - OBJECTIVE: To determine whether higher activity of daily living (ADL) limitation stages are associated with increased risk of hospitalization, particularly for ambulatory care sensitive (ACS) conditions. DATA SOURCE: Secondary data analysis, including 8,815 beneficiaries from 2005 to 2006 Medicare Current Beneficiary Survey (MCBS). STUDY DESIGN: ADL limitation stages (0-IV) were determined at the end of 2005. Hospitalization rates were calculated for 2006 and age adjusted using direct standardization. Multivariate negative binomial regression, adjusting for baseline demographic and health characteristics, with the outcome hospitalization count was performed to estimate the adjusted rate ratio of ACS and non-ACS hospitalizations for beneficiaries with ADL stages > 0 compared to beneficiaries without limitations. DATA COLLECTION: Baseline ADL stage and health conditions were assessed using 2005 MCBS data and count of hospitalization determined using 2006 MCBS data. PRINCIPAL FINDINGS: Referenced to stage 0, the adjusted rate ratios (95 percent confidence interval) for stage I to stage IV ranged from 1.9 (1.4-2.5) to 4.1 (2.2-7.8) for ACS hospitalizations compared with from 1.6 (1.3-1.9) to 1.8 (1.4-2.5) for non-ACS hospitalizations. CONCLUSIONS: Hospitalization rates for ACS conditions increased more dramatically with ADL limitation stage than did rates for non-ACS conditions. Adults with ADL limitations appear particularly vulnerable to potentially preventable hospitalizations for conditions typically manageable in ambulatory settings. PMID- 26990315 TI - Effect of Perioperative Synbiotic Treatment on Bacterial Translocation and Postoperative Infectious Complications after Pancreatoduodenectomy. AB - BACKGROUND/AIMS: This study investigated the effect of perioperative synbiotics on bacterial translocation to mesenteric lymph nodes (MLNs) and occurrence of infectious complications following pancreatoduodenectomy (PD; University Hospital Medical Information Network ID 000003705). METHODS: Patients who were scheduled to undergo PD were randomized to receive preoperative synbiotics or no synbiotics (control group). MLNs were harvested at laparotomy (MLN-1) and after the resection (MLN-2). Blood samples were collected before laparotomy (Blood-1) and on postoperative day 1 (Blood-2). Microorganisms in each sample were detected using a bacterium-specific ribosomal RNA-targeted reverse transcriptase quantitative polymerase chain reaction. RESULTS: Forty-four patients were included. In all samples, the bacterial detection rate in the MLN-1, MLN-2, Blood 1, and Blood-2 was lower in the synbiotics group than in the control group, although it did not reach a statistically significant difference. There was a significant correlation between the positivity of bacteria in the MLN-2 and Blood 2 samples (p = 0.009). The incidence rate of overall infectious complications was not significantly different between the 2 groups. Among various perioperative factors, the incidence of pancreatic fistula was the only factor that had a significant association with the incidence of infectious complications. CONCLUSION: The preoperative use of synbiotics did not affect the incidence of infectious complications following PD. PMID- 26990313 TI - Multi-locus Genotypes Underlying Temperature Sensitivity in a Mutationally Induced Trait. AB - Determining how genetic variation alters the expression of heritable phenotypes across conditions is important for agriculture, evolution, and medicine. Central to this problem is the concept of genotype-by-environment interaction (or 'GxE'), which occurs when segregating genetic variation causes individuals to show different phenotypic responses to the environment. While many studies have sought to identify individual loci that contribute to GxE, obtaining a deeper understanding of this phenomenon may require defining how sets of loci collectively alter the relationship between genotype, environment, and phenotype. Here, we identify combinations of alleles at seven loci that control how a mutationally induced colony phenotype is expressed across a range of temperatures (21, 30, and 37 degrees C) in a panel of yeast recombinants. We show that five predominant multi-locus genotypes involving the detected loci result in trait expression with varying degrees of temperature sensitivity. By comparing these genotypes and their patterns of trait expression across temperatures, we demonstrate that the involved alleles contribute to temperature sensitivity in different ways. While alleles of the transcription factor MSS11 specify the potential temperatures at which the trait can occur, alleles at the other loci modify temperature sensitivity within the range established by MSS11 in a genetic background- and/or temperature-dependent manner. Our results not only represent one of the first characterizations of GxE at the resolution of multi-locus genotypes, but also provide an example of the different roles that genetic variants can play in altering trait expression across conditions. PMID- 26990316 TI - Statin Effects on Exacerbation Rates, Mortality, and Inflammatory Markers in Patients with Chronic Obstructive Pulmonary Disease: A Review of Prospective Studies. AB - Chronic obstructive pulmonary disease (COPD) is a debilitating, irreversible disease with currently available therapies targeting symptom control and exacerbation reduction. A need for alternative disease-modifying therapies remains, specifically those that may have antiinflammatory and immunomodulatory properties that impact the pathophysiologic components of COPD. Statin drugs, the current gold standard for the treatment of dyslipidemia and prevention of cardiovascular disease (CVD), contain properties that affect the inflammatory disease processes seen in COPD. Several retrospective studies have demonstrated that statins may have a benefit in the reduction of morbidity and mortality in patients with COPD. This has led to prospective trials evaluating the impact of statins on various COPD-related outcomes. This article reviews the current body of prospective evidence for use of statins in patients with COPD. A search of the PubMed/Medline database of English-language articles was conducted from 1964 through November 2015; references of relevant articles were also reviewed for qualifying studies. Prospective studies of all types relating to statin use in patients with COPD were included if they had COPD- or respiratory-related outcomes; ultimately, eight studies were identified for this review. Statin effects on exacerbation rates, mortality, and inflammatory markers in patients with COPD are discussed. Strong prospective evidence does not currently exist to suggest that statins provide a clinical benefit in patients with COPD who do not have other CVD risk factors. Benefits from statins that have been illustrated are likely explained by their impact on underlying CVD risk factors rather than the COPD disease process. An opportunity exists for unanswered questions to be addressed in future studies. PMID- 26990317 TI - Comparison of US and CT on the effect on negative appendectomy and appendiceal perforation in adolescents and adults: A post-hoc analysis using propensity-score methods. AB - PURPOSE: To retrospectively compare ultrasound (US) and CT as the preoperative first-line imaging modality in terms of negative appendectomy rate (NAR) and appendiceal perforation rate (APR) in adolescents and adults with suspected appendicitis. METHODS: We included 2,030 patients in 11 sites who underwent appendectomy following US (n = 102) or CT (n = 1,928). Propensity-score (PS) adjusted and matched comparisons were conducted. Matching was performed with 1:1 and 1:3 ratios. Secondary analyses were performed by adding appendiceal perforation to PS model. RESULTS: The unadjusted NAR difference between the unmatched US and CT groups (8% [8/102] versus 3.8% [73/1,928]) was 4.1 percentage points (95% confidence interval, -1.2, -9.3; p = 0.133). The PS adjusted difference was 4.1 percentage points (-1.8, -10.0; p = 0.169). The differences after 1:1 (9% [8/94] versus 5% [5/94]) and 1:3 (9% [8/94] versus 3.0% [8/271]) matching were 3 (-4, -10, p = 0.39) and 5.6 (-0.4, -11.6, p = 0.069) percentage points, respectively. The unadjusted APR difference between the unmatched US and CT groups (22% [22/102] versus 23.8% [459/1,928]) was -2.2 percentage points ( 10.4, -6.0; p = 0.59). The PS-adjusted difference was -5.2 percentage points ( 13.3, -2.9; p = 0.21). The differences after 1:1 (19% [18/94] versus 24% [23/94]) and 1:3 (19% [18/94] versus 20.7% [56/271]) matching were -5 (-17, -6, p = 0.38) and -1.5 (-10.8, -7.8, p = 0.75) percentage points, respectively. CONCLUSIONS: The use of US instead of CT may increase NAR but does not significantly affect APR. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:401-410, 2016. PMID- 26990319 TI - Rhodium-Catalyzed Intramolecular [5+2] Cycloaddition of Inverted 3-Acyloxy-1,4 enyne and Alkyne: Experimental and Theoretical Studies. AB - By switching the position of the alkene and alkyne, a new type of 3-acyloxy-1,4 enyne (ACE) five-carbon building block was developed for Rh-catalyzed intramolecular [5+2] cycloaddition. An electron-withdrawing acyl group on the alkyne termini of the ACE was essential for a regioselective 1,2-acyloxy migration. This new method provided bicyclic [5.3.0]decatrienes that are different from previous methods because of the positions of the alkenes and the acyloxy group. Multiple mechanistic pathways become possible for this new [5+2] cycloaddition and they are investigated by computational studies. PMID- 26990318 TI - Noninvasive Transcutaneous Vagus Nerve Stimulation Decreases Whole Blood Culture Derived Cytokines and Chemokines: A Randomized, Blinded, Healthy Control Pilot Trial. AB - OBJECTIVES: The purpose of this study was to test the transcutaneous noninvasive vagus nerve stimulator (nVNS) (gammaCore(c)) device to determine if it modulates the peripheral immune system, as has been previously published for implanted vagus nerve stimulators. MATERIALS AND METHODS: A total of 20 healthy males and females were randomized to receive either nVNS or sham stimulation (SST). All subjects underwent an initial blood draw at 8:00 am, followed by stimulation with nVNS or SST at 8:30 am. Stimulation was repeated at 12:00 pm and 6:00 pm. Additional blood samples were withdrawn 90 min and 24 hour after the first stimulation session. After samples were cultured using the Myriad RBM TruCulture (Austin, TX) system (WBCx), levels of cytokines and chemokines were measured by the Luminex assay and statistical analyses within and between groups were performed using the Wilcoxon Signed Ranks Test and Mann-Whitney U with the statistical program R. RESULTS: A significant percent decrease in the levels of the cytokine interleukin [IL]-1beta, tumor necrosis factor [TNF] levels, and chemokine, interleukin [IL]-8 IL-8, macrophage inflammatory protein [MIP]-1alpha, and monocyte chemoattractant protein [MCP]-1 levels was observed in the nVNS group non-lipopolysaccharide (LPS)-stimulated whole blood culture (n-WBCx) at the 24-hour time point (p < 0.05). In SST group, there was a significant percent increase in IL-8 at 90 min post-stimulation (p < 0.05). At 90 min, the nVNS group had a greater percent decrease in IL-8 concentration (p < 0.05) compared to SST group. The nVNS group had a greater percent decrease in cytokines (TNF, IL-1beta) and chemokines (MCP-1 and IL-8) at 24 hour (p < 0.05) in comparison to SST. LPS stimulated whole blood cultures (L-WBCx) did not show a significant decrease in cytokine levels in either the nVNS or SST group across any time points. The nVNS group showed a significant percent increase in LPS-stimulated IL-10 levels at the 24-hour time point in comparison to SST. CONCLUSIONS: nVNS downregulates inflammatory cytokine release suggesting that nVNS may be an effective anti inflammatory treatment. PMID- 26990320 TI - A Long-Life Lithium Ion Battery with Enhanced Electrode/Electrolyte Interface by Using an Ionic Liquid Solution. AB - In this paper, we report an advanced long-life lithium ion battery, employing a Pyr14 TFSI-LiTFSI non-flammable ionic liquid (IL) electrolyte, a nanostructured tin carbon (Sn-C) nanocomposite anode, and a layered LiNi1/3 Co1/3 Mn1/3 O2 (NMC) cathode. The IL-based electrolyte is characterized in terms of conductivity and viscosity at various temperatures, revealing a Vogel-Tammann-Fulcher (VTF) trend. Lithium half-cells employing the Sn-C anode and NMC cathode in the Pyr14 TFSI LiTFSI electrolyte are investigated by galvanostatic cycling at various temperatures, demonstrating the full compatibility of the electrolyte with the selected electrode materials. The NMC and Sn-C electrodes are combined into a cathode-limited full cell, which is subjected to prolonged cycling at 40 degrees C, revealing a very stable capacity of about 140 mAh g(-1) and retention above 99 % over 400 cycles. The electrode/electrolyte interface is further characterized through a combination of electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) investigations upon cell cycling. The remarkable performances reported here definitively indicate that IL-based lithium ion cells are suitable batteries for application in electric vehicles. PMID- 26990321 TI - Pollen size strongly correlates with stigma depth among Pedicularis species. AB - Darwin proposed that pollen size should be positively correlated with stigma depth rather than style length among species given that pollen tubes first enter the stigma autotrophically, then grow through the style heterotrophically. However, studies often show a positive relationship between pollen size and style length. Five floral traits were observed to be correlated among 42 bumblebee pollinated Pedicularis species (Orobanchaceae) in which stigmas are distinct from styles. The phylogenetic independent contrast analysis revealed that pollen grain volume was more strongly correlated with stigma depth than with style length, consistent with Darwin's functional hypothesis between pollen size and stigma depth. PMID- 26990322 TI - Enveloped Lives: Practicing Health and Care in Lithuania. AB - This article analyzes informal medical payments that the majority of Lithuanians give or feel compelled to give to doctors before or after treatment. It focuses on how patients and their caretakers encounter, practice, and enact informal payments in health care and how these payments create a reality of health care that is not limited to an economic rationality. Within such a frame, rather than being considered a gift or bribe, it conceptualizes these little white envelopes as a practice of health and care. The article shows how an envelope of money given to a doctor transcends the material patient-doctor transaction and emerges as a productive force for coping with illness, medical encounters, and misfortunes. PMID- 26990323 TI - A systematic review and meta-analysis of screen time behaviour among North American indigenous populations. AB - Screen time (computer, television, video game and smartphone/tablet activity) is associated with increased obesity and other health risks. This systematic review evaluates screen time among North American Indigenous populations and compares it with that of North American Europeans. Electronic databases (e.g. MEDLINE and EMBASE) were searched, and citations cross-referenced. Included articles reported screen time among First Nations/American Indians, Metis, Inuit/Alaskan Natives or Native Hawaiians. From 788 citations evaluated, 40 identified articles report television, video game, computer and/or overall screen time. Overall screen time was 3.65 +/- 1.26 h day(-1) (n = 2,242, 8 articles) among Indigenous children/youth and 3.61 +/- 2.95 h day(-1) (n = 155, 1 article) among adults. Among children/youth, 66.0% (n = 11 256, 9 articles) reported less than 2 h day( 1) of television screen time, while only 52.8% (n = 2,458, 1 article) of adults reported this volume. Screen time was generally greater among male population, youth, First Nations/American Indians and overweight/obese individuals. Indigenous children/youth reported greater overall screen time than North American Europeans (4.81 +/- 2.84 h day(-1) , n = 1,182 vs. 3.40 +/- 2.81 h day( 1) , n = 2,785; 3 articles; p < 0.0001). Screen time is common among North American Indigenous populations. Further research evaluating interventions to reduce screen time and chronic disease risks is required. PMID- 26990324 TI - High-fat high-sucrose diet leads to dynamic structural and inflammatory alterations in the rat vastus lateralis muscle. AB - The influence of obesity on muscle integrity is not well understood. The purpose of this study was to quantify structural and molecular changes in the rat vastus lateralis (VL) muscle as a function of a 12-week obesity induction period and a subsequent adaptation period (additional 16-weeks). Male Sprague-Dawley rats consumed a high-fat, high-sucrose (DIO, n = 40) diet, or a chow control-diet (n = 14). At 12-weeks, DIO rats were grouped as prone (DIO-P, top 33% of weight change) or resistant (DIO-R, bottom 33%). Animals were euthanized at 12- or 28 weeks on the diet. At sacrifice, body composition was determined and VL muscles were collected. Intramuscular fat, fibrosis, and CD68+ cells were quantified histologically and relevant molecular markers were evaluated using RT-qPCR. At 12 and 28-weeks post-obesity induction, DIO-P rats had more mass and body fat than DIO-R and chow rats (p < 0.05). DIO-P and DIO-R rats had similar losses in muscle mass, which were greater than those in chow rats (p < 0.05). mRNA levels for MAFbx/atrogin-1 were reduced in DIO-P and DIO-R rats at 12- and 28-weeks compared to chow rats (p < 0.05), while expression of MuRF1 was similar to chow values. DIO-P rats demonstrated increased mRNA levels for pro-inflammatory mediators, inflammatory cells, and fibrosis compared to DIO-R and chow animals, despite having similar levels of intramuscular fat. The down-regulation of MAFbx/atrogin 1 may suggest onset of degenerative changes in VL muscle integrity of obese rats. DIO-R animals exhibited fewer inflammatory changes compared to DIO-P animals, suggesting a protective effect of obesity resistance on local inflammation. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2069-2078, 2016. PMID- 26990326 TI - Sarcoidosis. AB - We present a 28-year-old man with a one-year history of cutaneous lesions in old scars and tattoos with concomitant subcutaneous nodules and myopathy. A skin biopsy specimen showed cutaneous sarcoidosis. We discuss the multiple aspects of this case, which represent unique presentations of this systemic disease as well as review isomorphic and isotopic responses. PMID- 26990325 TI - Arabidopsis CLAVATA1 and CLAVATA2 receptors contribute to Ralstonia solanacearum pathogenicity through a miR169-dependent pathway. AB - Bacterial wilt caused by Ralstonia solanacearum is one of the most destructive bacterial plant diseases. Although many molecular determinants involved in R. solanacearum adaptation to hosts and pathogenesis have been described, host components required for disease establishment remain poorly characterized. Phenotypical analysis of Arabidopsis mutants for leucine-rich repeat (LRR) receptor-like proteins revealed that mutations in the CLAVATA1 (CLV1) and CLAVATA2 (CLV2) genes confer enhanced disease resistance to bacterial wilt. We further investigated the underlying mechanisms using genetic, transcriptomic and molecular approaches. The enhanced resistance of both clv1 and clv2 mutants to the bacteria did not require the well characterized CLV signalling modules involved in shoot meristem homeostasis, and was conditioned by neither salicylic acid nor ethylene defence-related hormones. Gene expression microarray analysis performed on clv1 and clv2 revealed deregulation of genes encoding nuclear transcription factor Y subunit alpha (NF-YA) transcription factors whose post transcriptional regulation is known to involve microRNAs from the miR169 family. Both clv mutants showed a defect in miR169 accumulation. Conversely, overexpression of miR169 abrogated the resistance phenotype of clv mutants. We propose that CLV1 and CLV2, two receptors involved in CLV3 perception during plant development, contribute to bacterial wilt through a signalling pathway involving the miR169/NF-YA module. PMID- 26990327 TI - Acrokeratoelastoidosis. AB - Acrokeratoelastoidosis is a rare palmoplantar keratoderma. We report the case of a 32-year old man with multiple keratotic papules and plaques on the peripheral margins of his hands and feet. Histopathologic evaluation showed compact orthokeratosis; Verhoeff van Gieson stain showed thin and fragmented elastic fibers. The differential diagnosis includes focal acral hyperkeratosis, which has a similar presentation but with normal elastic fibers. Treatment of acrokeratoelastoidosis is often disappointing, with minimal response to topical glucocorticoids, keratolytics, retinoids, cryotherapy, and lasers. PMID- 26990328 TI - Possible photoactivated dermatitis with features of post-inflammatory pigmentary alteration (PIPA) and rosacea. AB - Cutaneous flushing and facial erythema are common dermatologic conditions that elicit a wide differential diagnosis that includes rosacea, seborrheic dermatitis, photodermatitis, connective-tissue diseases, carcinoid syndrome, and mastocytosis. Herein we present an usual case of a mask-like rosacea-PIPA overlap that occurred in a patient with prior history of rectal carcinoid tumor and a negative systemic evaluation. PMID- 26990329 TI - Squamous-cell carcinoma in situ. AB - We present a 30-year-old woman with atopic dermatitis and ichthyosis vulgaris and a one-year history of an erythematous, scaly plaque on the dorsal surface of her right hand, which developed three years after an accidental exposure to prolonged ultraviolet C (UVC) radiation in a laboratory accident. The plaque, which was initially treated as eczematous dermatitis, was eventually identified histopathologically as squamous-cell carcinoma in situ. Although causation is not definitive, this case is the first to describe development of non-melanoma skin cancer (NMSC) in an area of skin known to be acutely exposed to UVC radiation. As UVC radiation becomes a more frequently used anti-microbial technology, UVC radiation may become a more commonly identified risk factor in the development of NMSC. PMID- 26990330 TI - Angiolymphoid hyperplasia with eosinophilia. AB - Angiolymphoid hyperplasia with eosinophilia is a rare, benign, vascular proliferation that presents as dome-shaped, light-pink-to-red-brown papules or subcutaneous masses that lack distinguishing surface changes. The condition typically presents as a single lesion or multiple lesions that involve contiguous areas. The pathogenesis is poorly understood. Angiolymhpoid hyperplasia with eosinophilia has been associated with antecedent trauma, T-cell proliferation, infection, and hormone imbalance. This report details a case of widespread angiolymphoid hyperplasia with eosinophilia that flared while the patient was pregnant. PMID- 26990331 TI - Extragenital bullous lichen sclerosus. AB - Lichen sclerosus (LS) is a chronic, inflammatory dermatosis that is characterized by pruritic, white, atrophic plaques that classically affect the anogenital region of postmenopausal women. Extragenital involvement also may occur with several reported morphologic variants. Extragenital bullous LS is a rare variant, which presents as flaccid bullae that favor the trunk and proximal aspects of the extremities. The treatment of extragenital bullous LS is similar to that of genital LS. However, extragenital LS is often less responsive and may present a therapeutic challenge. We describe a 65-year-old woman with a two-year history of vulvar and extragenital LS, who developed a bullous eruption within a pre existing patch of lichen sclerosis on the breast. We review the clinical and histopathologic features of extragenital bullous LS and discuss current treatment options, which include those for recalcitrant cases. PMID- 26990332 TI - Benign familial pemphigus (Hailey-Hailey disease). AB - A 56-year-old man presented with a 15-year history of scaly red plaques on the trunk and axillae. Skin biopsy was consistent with Hailey-Hailey disease. His condition was refractory to multiple therapies, which included topical and oral antibiotics and topical, intralesional, and oral glucocorticoids. Treatment with subcutaneous botulinum toxin type A at the axillae and on the back led to a nearly complete resolution of plaques in those areas. Botulinum toxin type A should be considered in patients with extensive Hailey-Hailey disease who are fail traditional therapies. PMID- 26990333 TI - Piloleiomyomas in multiple cutaneous and uterine leiomyoma syndrome (hereditary leiomyomatosis and renal cell cancer or Reed syndrome). AB - Multiple cutaneous and uterine leiomyoma (MCL), or Reed syndrome is an uncommon condition that includes cutaneous piloleiomyomas and internal neoplasms of the uterus and kidney. Clinical findings include clusters of variably-painful, skin colored-to-red-brown papules. Genetic testing shows germline mutations in the gene encoding fumarate hydratase. We describe a patient with MCL who presented with subtle cutaneous findings. We believe it is important that dermatologists consider a diagnosis of MCL when presented with patients with small painful dermal papules. PMID- 26990334 TI - Generalized granuloma annulare in a folliculocentric distribution. AB - We present a 69-year-old man with type 2 diabetes mellitus and a five-year history of an eruption of follicular pustules, papules, and nodules, which was identified histopathologically as folliculocentric granuloma annulare (GA). Folliculocentric generalized GA is a rarely reported variant of GA, in which the the palisading histiocytes form focal granulomas in a follicular pattern. In this case, the GA may represent an isotopic phenomenon, with lesions developing in hair follicles that were previously affected by a suppurative folliculitis. PMID- 26990335 TI - Eosinophilic dermatitis of hematologic malignancy. AB - Eosinophilic dermatosis of hematologic malignancy is a rare, paraneoplastic phenomenon that presents as a pruritic papular or vesicular eruption that is clinically and histopathologically similar to insect bites. We present a 56-year old man with multiple relapses of diffuse large B cell lymphoma with a typical presentation of pruritic papules and vesicles on the extremities that correlate with a recent relapse of his lymphoma. PMID- 26990336 TI - Periungual pyogenic granuloma formation in a patient with complex regional pain syndrome. AB - Peripheral nerve injury has been associated with the development of periungual pyogenic granuolomas (PGs). We present the case of a 39-year-old woman with an eight-month history of periungual PGs in the setting of a four-to-five year history of a traumatic inciting event that produced symptoms consistent with complex regional pain syndrome (CRPS). Although recurrent, these periungual PGs have remitted after treatment with topical timolol maleate. This case exhibits an underappreciated association between peripheral neurologic abnormalities, which include CRPS, and cutaneous abnormalities. It also presents evidence that supports the concept that PGs that are not appropriate for surgical treatments may be treated with topical timolol maleate. PMID- 26990337 TI - Paraneoplastic erythema annulare centrifugum eruption (PEACE). AB - Erythema annulare centrifugum (EAC) is a reactive erythema with distinct, annular, erythematous plaques with trailing scale. This condition has been associated with various etiologies, which include an associated malignant condition. EAC with cancers or paraneoplastic erythema annulare centrifugum eruptions (PEACE), is more likely to be associated with lymphoproliferative malignancies such as lymphomas and leukemias. Histopathologic features include a superficial and deep, lymphohistiocytic perivascular infiltrate. We present a patient with a history of diffuse large B cell lymphoma in remission for two years, who presented with a one-year history of EAC. PMID- 26990338 TI - Photodistributed granuloma annulare. AB - Annular elastolytic giant cell granuloma (AEGCG) is a controversial entity that is considered by many to be a variant of granuloma annulare (GA). The majority of cases of AEGCG occur in Caucasian women (3:2) between the ages of 40 and 70, with the distribution of the mostly annular lesions favoring exposed areas of skin and rarely involving covered skin. The most common systemic association has been with diabetes mellitus. We present a 52-year-old woman with an asymptomatic, annular, erythematous, photodistributed eruption of two-years duration. As part of her evaluation, it was detected that she had a hemoglobin A1C of 10.3% and a diagnosis of diabetes mellitus was made. We review the literature on the clinical and histopathologic features of GA and AEGCG and the overlap between these entities. PMID- 26990339 TI - Multiple eruptive dermatofibromas. AB - We report a 34 year-old woman with psoriasis, systemic lupus erythematosus (SLE), and recent anti-TNFa therapy, who presented with multiple, eruptive dermatofibromas (MEDF). Although the pathogenesis of MEDF remains unknown, there is substantial evidence that this phenomenon represents an aberrant immune response. Like the more common presentation of solitary dermatofibromas, these lesions are benign, and no treatment is required. However, MEDF is increasingly recognized as a sign of immune dysregulation and an appropriate work-up should be initiated to identify an underlying cause in patients without a known trigger. PMID- 26990340 TI - Keratolysis exfoliativa. AB - Keratolysis exfoliativa (KE) is a palmoplantar eruption of air-filled bullae on an erythematous base, which results in lamellar peeling with hallmark superficial collarettes of scale. It is distinct from other diseases of volar skin, such as dyshidrosis, contact dermatitis, tinea, epidermolysis bullosa, and acral skin peeling. We present a 55-year-old woman with extensive disease on the hands and feet, who failed to respond to standard topical therapy but showed a marked dose response improvement with the use of oral acitretin. Recent histopathologic and molecular studies have linked KE to premature corneo-desmosomal disruption. Acitretin has previously been used to treat diseases of abnormal corneocyte desquamation, for example Netherton's disease. To the best of our knowledge, this report is the first that documents the efficacy of the use of systemic acitretin in KE. PMID- 26990341 TI - Mycobacterium avium complex infection. AB - We report the case of a 30-year-old woman with a three-year history of papules, nodules, and multiple ulcers of the left lower extremity. A skin biopsy specimen showed dermal fibrosis and patchy granulomatous inflammation in the upper-to-mid dermis that was associated with a perivascular, lymphohistiocytic infiltrate along with granulomas and necrosis in the subcutaneous fat. Tissue culture showed Mycobacterium avium complex infection. Clinical manifestations of cutaneous nontuberculous mycobacterial infections are discussed as well as their potential association with pedicures. PMID- 26990342 TI - IgA vasculitis (Henoch-Schonlein purpura). AB - We report the first case of direct immunoflourescence-proven immunoglobulin A (IgA) vasculitis associated with influenza infection in an adult patient. IgA vasculitis, which was previously known as Henoch-Schonlein purpura, is the most common systemic vasculitis in children but rarely occurs in adults. Disease onset often occurs after upper respiratory tract infections that are caused by adenovirus or enterovirus. The American College of Rheumatology defines IgA vasculitis by the presence of any two of the following four criteria: age <= 20 years at disease onset, palpable purpura, acute abdominal pain, and a biopsy specimen that shows granulocytes in the walls of small arterioles or venules. Purpura, abdominal pain, and arthralgia comprise the classic triad. Renal involvement may be severe, especially in adults. Treatment is most often supportive but glucocorticoids and/or immunosuppressive agents are recommended in severe or refractory cases. PMID- 26990343 TI - Lupus miliaris disseminatus faciei. AB - Lupus miliaris disseminatus faciei (LMDF) is a rare, inflammatory condition, which is characterized by red-brown and yellow-brown papules on the face, with characteristic involvement of the eyelids and with histopathologic findings of suppurative and granulomatous folliculitis and dermatitis. The etiology of this disease is not known, but retinoids, anti-inflammatory, immunosuppressive, and antimicrobial medications are utilized to treat the condition with variable results. We present the case of a patient with LMDF that has thus far been refractory to treatment. PMID- 26990344 TI - Chronic actinic dermatitis occurring in an adult with atopic dermatitis. AB - Chronic actinic dermatitis (CAD) is a photosensitivity disorder that is characterized by a persistent eczematous eruption in sun-exposed sites. The hallmark of CAD is a reduced minimal erythema dose (MED) to ultraviolet B (UVB), ultraviolet A (UVA), and/or to visible light, which makes phototesting the essential diagnostic investigation. The uncommon subgroup of patients with atopic dermatitis (AD) that are affected by CAD has primarily been described in young patients in the United Kingdom. We present an atopic adult women with CAD who was diagnosed years after symptoms began. We believe it is important that dermatologists perform phototests on AD patients with features of a photoaggravated dermatitis in order to avoid delay in diagnosis of a true photosensitivity condition and provide appropriate management. PMID- 26990345 TI - Nodular amyloidosis. AB - Nodular amyloidosis is the rarest form of primary cutaneous amyloidosis. We report the case of a 74-year-old woman with an eight-year history of asymptomatic, hyperpigmented plaques on the pretibial areas. A skin biopsy specimen showed deposits of amorphous eosinophilic material that extended throughout the dermis with apple-green birefringence with a Congo-red stain, which established a diagnosis of nodular amyloidosis. Patients with nodular amyloidosis should be evaluated for systemic disease and followed appropriately due to a small risk of progression to systemic amyloidosis. PMID- 26990346 TI - Primary diffuse macular amyloidosis. AB - We present a 53-year-old woman with diffuse macular amyloidosis. We discuss the clinical manifestations, pathophysiologic mechanisms, and associations of cutaneous macular amyloidosis. PMID- 26990347 TI - Linear atrophoderma of Moulin. AB - We present a 40-year-old woman with asymptomatic, linear, hyperpigmented atrophic plaques in a Blaschkoid distribution on the right back and right upper extremity that is consistent with a diagnosis of linear atrophoderma of Moulin. Clinical lesions developed with a biphasic pattern in late adolescence and in adulthood. The pathogenesis of this acquired, progressive Blaschkolinear dermatosis may hold insight into the pathogenesis of this rare dermatologic condition, as well as other dermotoses, which include those resulting from post-zygotic genetic mosaicism. PMID- 26990348 TI - Clinical factors and socio-demographic characteristics associated with dental trauma in children: a systematic review and meta-analysis. AB - OBJECTIVE: The aim of this systematic review and meta-analysis was to search for scientific evidence regarding the factors associated with traumatic dental injury (TDI) in the primary dentition. METHODOLOGY: An electronic search addressing factors associated with TDI was conducted in the PubMed, ISI, LILACS, Cochrane Library, and Embase databases. Data were extracted and analyzed regarding risk factors, statistical test, effect measures, and study design. RESULTS: The online search strategy led to the initial retrieval of 2566 articles. After evaluating the titles and abstracts, 24 papers were selected for complete review and data collection. TDI was associated with males (OR: 1.24; 95%CI: 1.09-1.41), inadequate lip coverage (OR: 1.81; 95%CI: 1.50-2.17), overbite (OR: 1.438; 95%CI: 0.94-2.19), and age (1 vs 2 years - OR: 0.47; 95%CI: 0.38-0.58; 2 vs 3 years - OR: 0.78; 95%CI: 0.67-0.91; 3 vs 4 years - OR: 0.82; 95%CI: 0.71-0.95). Overjet and anterior open bite were associated with TDI in the majority of studies. CONCLUSIONS: Males, older children, and those with inadequate lip coverage, overbite, or overjet are more likely to have TDI in the primary dentition. PMID- 26990349 TI - Health Security and Risk Aversion. AB - Health security has become a popular way of justifying efforts to control catastrophic threats to public health. Unfortunately, there has been little analysis of the concept of health security, nor the relationship between health security and other potential aims of public health policy. In this paper I develop an account of health security as an aversion to risky policy options. I explore three reasons for thinking risk avoidance is a distinctly worthwhile aim of public health policy: (i) that security is intrinsically valuable, (ii) that it is necessary for social planning and (iii) that it is an appropriate response to decision-making in contexts of very limited information. Striking the right balance between securing and maximizing population health thus requires a substantive, and hitherto unrecognized, value judgment. Finally, I critically evaluate the current health security agenda in light of this new account of the concept and its relationship to the other aims of public health policy. PMID- 26990350 TI - Liver iron is a major regulator of hepcidin gene expression via BMP/SMAD pathway in a rat model of chronic renal failure under treatment with high rHuEPO doses. AB - Hepcidin is the major central regulator of iron metabolism, controlling iron absorption and mobilization. Considering its interaction with several factors that are altered in chronic kidney disease (CKD), particularly in hyporesponsive CKD patients under therapy with high recombinant human erythropoietin (rHuEPO) doses, it was aimed to study the impact of increasing rHuEPO doses on the regulation of iron-hepcidin metabolism. The blood, cellular, and tissue studies, using the remnant kidney rat model of CKD induced by 5/6 nephrectomy, under rHuEPO (100, 200, 400, and 600 IU/Kg body weight [BW]/week) treatment during 3 weeks were performed. It was found that the rHuEPO stimulus triggered a first wave to achieve correction of anemia, by inhibiting hepcidin synthesis, favoring erythropoiesis and iron absorption; this continuous stimulus enhanced iron absorption leading to iron overload, as showed by the hepatic iron deposits found in rats treated with higher rHuEPO dose that seems to trigger the upregulation of hepcidin synthesis through the activation of the BMP6/SMAD pathway. The data suggested that liver iron overload was an important stimuli for hepcidin synthesis, stronger than the inhibitory effect of high rHuEPO doses; moreover, the findings raised the hypothesis that when high inflammation (triggering hepcidin expression) was associated with increased iron stores in hemodialysis patients, hepcidin expression was also upregulated via BMP6, enhancing hepcidin synthesis, leading, therefore, to worsening of anemia and, eventually, to a hyporesponse/resistance to rHuEPO therapy. (c) 2016 BioFactors, 42(3):296-306, 2016. PMID- 26990351 TI - Projected impacts of 21st century climate change on diapause in Calanus finmarchicus. AB - Diapause plays a key role in the life cycle of high latitude zooplankton. During diapause, animals avoid starving in winter by living in deep waters where metabolism is lower and met by lipid reserves. Global warming is therefore expected to shorten the maximum potential diapause duration by increasing metabolic rates and by reducing body size and lipid reserves. This will alter the phenology of zooplankton, impact higher trophic levels and disrupt biological carbon pumps. Here, we project the impacts of climate change on the key North Atlantic copepod Calanus finmarchicus under IPCC RCP 8.5. Potential diapause duration is modelled in relation to body size and overwintering temperature. The projections show pronounced geographic variations. Potential diapause duration reduces by more than 30% in the Western Atlantic, whereas in the key overwintering centre of the Norwegian Sea it changes only marginally. Surface temperature rises, which reduce body size and lipid reserves, will have a similar impact to deep-water changes on diapause in many regions. Because deep-water warming lags that at the surface, animals in the Labrador Sea could offset warming impacts by diapausing in deeper waters. However, the ability to control diapause depth may be limited. PMID- 26990352 TI - Treat to target-what is realistic in Australian practice today? PMID- 26990353 TI - Effectiveness of a computerized decision support system for anticoagulation management in hemodialysis patients: A before-after study. AB - Introduction The risk-benefit profile for warfarin anticoagulation in hemodialysis (HD) patients differs compared with the non-HD population. HD patients are at increased risk of both thromboembolism and bleeding related to anticoagulation therapy. In addition, anticoagulation control may be more difficult to achieve in the HD population due to frequent comorbidities, subclinical Vitamin K deficiency, altered pharmacokinetics due to uremia and the concurrent use of multiple medications. While computerized decision support systems (CDSS) to assist with anticoagulation management are safe and effective in the non-HD population, they have not been well studied in HD outpatients. Methods A before-after study compared anticoagulation control for HD outpatients receiving warfarin at a tertiary medical center in Canada during two time periods: an initial period of nephrologist-led anticoagulation management and a second period after implementation of a pharmacist-led, CDSS-assisted anticoagulation management strategy. Findings Forty-two patients were included. Following implementation of the CDSS-assisted strategy, there was no significant change in median therapeutic time-in-range (3.7% difference (IQR, -9.5% to 20.6%); P = 0.247). Median change in INR testing frequency was 1.2 (IQR, 0.1-2.2; P = 0.0001) fewer tests per patient per month, which equates to approximately 15 fewer tests per patient per year. Adverse events were similar. Discussion Implementing a CDSS-assisted strategy for anticoagulation management in HD outpatients is effective. Doing so may lead to modest cost savings related to less frequent INR testing. PMID- 26990355 TI - Effect of Transition Metals on Polysialic Acid Structure and Functions. AB - Polysialic acid (PSA) is one of the most abundant glycopolymer present in embryonic brain, and it is known to be involved in key roles such as plasticity in the central nervous system, cell adhesion, migration and localization of neurotrophins. However, in adult brain, its expression is quite low. The exception to this is in Alzheimer's disease (AD) brain, where significantly increased levels of polysilylated neural cell adhesion molecule (PSA-NCAM) have been reported. Here, we confirm the role of PSA as a metal chelator, allowing it to decrease cytotoxicity caused by high levels of transition metals, commonly found in AD brain, and as a regulator of cell behavior. UV-visible (UV-vis) and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and isothermal titration calorimetry (ITC) techniques were used to investigate the assembly of PSA-metals complexes. These PSA-metal complexes exhibited less toxicity compared to free metal ions, and in particular, the PSA-Cu(2+) complex synergistically promoted neurite outgrowth in PC12 cells. PMID- 26990354 TI - Carotid body modulation in systolic heart failure from the clinical perspective. AB - Augmented sensitivity of peripheral chemoreceptors (PChS) is a common finding in systolic heart failure (HF). It is related to lower left ventricle systolic function, higher plasma concentrations of natriuretic peptides, worse exercise tolerance and greater prevalence of atrial fibrillation compared to patients with normal PChS. The magnitude of ventilatory response to the activation of peripheral chemoreceptors is proportional to the level of heart rate (tachycardia) and blood pressure (hypertension) responses. All these responses can be measured non-invasively in a safe and reproducible fashion using different methods employing either hypoxia or hypercapnia. Current interventions aimed at modulation of peripheral chemoreceptors in HF are focused on carotid bodies (CBs). There is a clear link between afferent signalling from CBs and sympathetic overactivity, which remains the priority target of modern HF treatment. However, CB modulation therapies may face several potential obstacles: (1) As evidenced by HF trials, an excessive inhibition of sympathetic system may be harmful. (2) Proximity of critical anatomical structures (important vessels and nerves) makes surgical and transcutaneous interventions on CB technically demanding. (3) Co existence of atherosclerosis in the area of carotid artery bifurcation increases the risk of central embolic events related to CB modulation. (4) The relative contribution of CBs vs. aortic bodies to sympathetic activation in HF patients is unclear. (5) Choosing optimal candidates for CB modulation from the population of HF patients may be problematic. (6) There is a risk of nocturnal hypoxia following CB ablation - mostly after bilateral procedures and in patients with concomitant obstructive sleep apnoea. PMID- 26990356 TI - Colonic mucosubmucosal elongated polyp: report of a series of 14 cases and review of the literature. AB - AIMS: Most colorectal polyps can be reliably assigned to one of the known polyp categories, but a subset of polyps named colonic mucosubmucosal elongated polyps (CMSEPs) do not fall into any of these categories. First described in the Japanese literature, CMSEPs seem to be under-recognized in the Western literature. The aims of this study were to describe the clinicopathological features of 14 CMSEPs, discuss potential pathogenetic mechanisms, and increase awareness of this entity among pathologists. METHODS AND RESULTS: Fourteen pedunculated colorectal polyps that met the histopathological criteria for CMSEP (as described by Matake et al. and Alizart et al.) were assessed (12 males and two females; mean age 59.7 years). Five polyps were located in the sigmoid colon, four in the rectum, two in the descending colon, and three in the colon not otherwise specified. Nine of 14 polyps were discovered incidentally: two of nine on routine screening colonoscopy, two of nine on surveillance colonoscopy for inflammatory bowel disease (IBD), and five of nine upon surgical intervention for carcinoma or IBD. None coexisted with diverticular disease. The polyps were long and slender, varied from 5 to 30 mm in length (mean 15.9 mm), and showed a normal looking colonic mucosal layer and underlying loose submucosa with thick-walled and congested blood vessels and lymphatics. CONCLUSIONS: CMSEPs show subtle but distinctive pathological features, and occur in normal and diseased colons. Pathologists need to be aware of this entity, to avoid confusion with other more commonly encountered colorectal polyps. With increasing colon cancer screening programmes and surveillance colonoscopy, it is likely that CMSEPs will be encountered more often. PMID- 26990357 TI - Dopaminergic variants in siblings at high risk for autism: Associations with initiating joint attention. AB - Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) exhibit lower levels of initiating joint attention (IJA; sharing an object or experience with a social partner through gaze and/or gesture) than low risk siblings of children without ASD. However, high-risk siblings also exhibit substantial variability in this domain. The neurotransmitter dopamine is linked to brain areas associated with reward, motivation, and attention, and common dopaminergic variants have been associated with attention difficulties. We examined whether these common dopaminergic variants, DRD4 and DRD2, explain variability in IJA in high-risk (n = 55) and low-risk (n = 38) siblings. IJA was assessed in the first year during a semi-structured interaction with an examiner. DRD4 and DRD2 genotypes were coded according to associated dopaminergic functioning to create a gene score, with higher scores indicating more genotypes associated with less efficient dopaminergic functioning. Higher dopamine gene scores (indicative of less efficient dopaminergic functioning) were associated with lower levels of IJA in the first year for high-risk siblings, while the opposite pattern emerged in low-risk siblings. Findings suggest differential susceptibility-IJA was differentially associated with dopaminergic functioning depending on familial ASD risk. Understanding genes linked to ASD-relevant behaviors in high-risk siblings will aid in early identification of children at greatest risk for difficulties in these behavioral domains, facilitating targeted prevention and intervention. Autism Res 2016, 9: 1142-1150. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26990358 TI - Role of microRNAs in primary central nervous system lymphomas. AB - Primary central nervous system lymphomas (PCNSL) are extranodal non-Hodgkin lymphomas arising exclusively inside the CNS, and account for about 3% of primary intracranial tumours. This tumour lacks systemic manifestations and prognosis of patients with PCNSL remains poor despite recent advancement of chemoradiotherapy. MicroRNAs are small non-coding RNAs that post-transcriptionally downregulate gene expression by binding to target mRNAs, inducing their degradation or translational repression. MicroRNAs play significant roles in almost all malignancy-related biological processes, including cell proliferation, differentiation, apoptosis and metabolism. Many deregulated miRNAs has been identified in PCNSL but their biological significance remains to be fully elucidated. In this review, we summarize current evidence regarding the pathogenic role of PCNSL-associated microRNAs and their potential applications for diagnosis and prognostication of this deadly disease. PMID- 26990359 TI - Detection of an EGFR mutation in cytological specimens of lung adenocarcinoma. AB - OBJECTIVE: Epidermal growth factor receptors (EGFR) mutation status is crucial for the prediction of a tumour response to treatment with EGFR tyrosine kinase (EGFR-TK) inhibitors. The aim of the study was to establish a protocol for the detection of EGFR-activating somatic mutations on cytological samples collected using a standard bronchoscopy procedure and to determine the frequency of EGFR mutations among pre-selected Croatian patients with non-small cell lung cancer (NSCLC) of an adenocarcinoma histological subtype. METHODS: A total of 177 cytological samples were collected from the patients diagnosed with NSCLC. DNA was isolated from the cytological material recovered from the fixed and stained slides. EGFR mutations were analysed using the polymerase chain reaction (PCR)- mediated Sanger sequencing method. RESULTS: Out of 177 collected samples, EGFR mutation analyses were successfully performed on 167 samples (94.4%); 77 (46.1%) of these were from male and 90 (53.9%) from female patients. EGFR mutations/deletions were found in 33 (19.8%) of the tested patients; exon 19 deletions in 17 (10.2%) and point mutations of exon 21 in 16 (9.6%) patients. CONCLUSION: The PCR-mediated Sanger sequencing method was found to be reproducible and reliable. Cytological samples can be used successfully to determine the EGFR mutation status in NSCLC patients providing information for targeted therapy at an early stage of the disease. PMID- 26990360 TI - Extracellular matrix components supporting human islet function in alginate-based immunoprotective microcapsules for treatment of diabetes. AB - In the pancreas, extracellular matrix (ECM) components play an import role in providing mechanical and physiological support, and also contribute to the function of islets. These ECM-connections are damaged during islet-isolation from the pancreas and are not fully recovered after encapsulation and transplantation. To promote the functional survival of human pancreatic islets, we tested different ECMs molecules in alginate-encapsulated human islets. These were laminin derived recognition sequences, IKVAV, RGD, LRE, PDSGR, collagen I sequence DGEA (0.01 - 1.0 mM), and collagen IV (50 - 200 ug/mL). Interaction with RGD and PDSGR promoted islet viability and glucose induced insulin secretion (GIIS) when it was applied at concentrations ranging from 0.01 - 1.0 mM (p < 0.05). Also the laminin sequence LRE contributed to enhanced GIIS but only at higher concentrations of 1 mM (p < 0.05). Collagen IV also had beneficial effects but only at 50 ug/ml and no further improvement was observed at higher concentrations. IKVAV and DGEA had no effects on human islets. Synergistic effects were observed by adding Collagen(IV)-RGD, Collagen(IV)-LRE, and Collagen(IV)-PDSGR to encapsulated human islets. Our results demonstrate the potential of specific ECM components in support of functional survival of human encapsulated and free islet grafts. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1788-1796, 2016. PMID- 26990361 TI - Repeated transcranial low-level laser therapy for traumatic brain injury in mice: biphasic dose response and long-term treatment outcome. AB - We previously showed that near-infrared laser photobiomodulation (PBM) (810 nm, CW, 18 J/cm2 , 25 mW/cm2 ) delivered to the mouse daily for 3-days after a controlled cortical impact traumatic brain injury (TBI) gave a significant improvement in neurological/cognitive function. However the same parameters delivered 14X daily gave significantly less benefit. This biphasic dose response intrigued us, and we decided to follow the mice that received 3X or 14X laser treatments out to 56-days post-TBI. We found the 14X group showed worse neurological function than the no-treatment TBI group at 2-weeks, but started to improve steadily during the next 6-weeks, and by 56-days were significantly better than the no-treatment TBI mice, but still worse than the 3X mice. A marker of activated glial cells (GFAP) was significantly increased in the brain regions (compared to both untreated TBI and 3X groups) at 4-weeks in the 14X group, but the GFAP had fallen to low levels in both 3X and 14X groups by 8-weeks. We conclude that an excessive number of laser-treatments delivered to mice can temporarily inhibit the process of brain repair stimulated by tPBM, but then the inhibitory effect ceases, and brain repair can resume. The mechanism may be temporary induction of reactive gliosis. PMID- 26990363 TI - Using OSCEs to test students' documentation skills. PMID- 26990362 TI - Autobiographical Memory Deficits in Alcohol-Dependent Patients with Short- and Long-Term Abstinence. AB - BACKGROUND: Autobiographical memory (AM) enables the storage and retrieval of life experiences that allow individuals to build their sense of identity. Several AM impairments have been described in patients with alcohol abuse disorders without assessing whether such deficits can be recovered. This cross-sectional study aimed to identify whether the semantic (SAM) and episodic (EAM) dimensions of AM are affected in individuals with alcohol dependence after short-term abstinence (STA) or long-term abstinence (LTA). A second aim of this study was to examine the factors that could disrupt the efficiency of semantic and episodic AM (the impact of depression severity, cognitive functions, recent or early traumatic events, and drinking history variables). METHODS: After clinical and cognitive evaluations (alcohol consumption, depression, anxiety, IQ, memory performance), AM was assessed with the Autobiographical Memory Interview in patients with recent (between 4 and 6 weeks) and longer (at least 6 months) abstinence. Participants were asked to retrieve the number and nature of traumatic or painful life experiences in recent or early life periods (using the Childhood Traumatic Events Scale). RESULTS: The 2 abstinent groups had lower global EAM and SAM scores than the control group. These scores were comparable for both abstinent groups. For childhood events, no significant differences were observed in SAM for both groups compared with control participants. For early adulthood and recent events, both STA and LTA groups had lower scores on both SAM and EAM. Moreover, there was a negative correlation between the length of substance consumption and SAM scores. CONCLUSIONS: This study highlighted a specific AM disorder in both episodic and semantic dimensions. These deficits remained after 6 months of abstinence. This AM impairment may be explained by compromised encoding and consolidation of memories during bouts of drinking. PMID- 26990364 TI - Computer technology for self-management: a scoping review. AB - AIMS AND OBJECTIVES: The purpose of this scoping review of literature is to explore the types of computer-based systems used for self-management of chronic disease, the goals and success of these systems, the value added by technology integration and the target audience for these systems. BACKGROUND: Technology is changing the way health care is provided and the way that individuals manage their health. Individuals with chronic diseases are now able to use computer based systems to self-manage their health. These systems have the ability to remind users of daily activities, and to help them recognise when symptoms are worsening and intervention is indicated. However, there are many questions about the types of systems available, the goals of these systems and the success with which individuals with chronic illness are using them. DESIGN: This is a scoping review in which the Cumulative Index of Nursing and Allied Health Literature, PubMed and IEEE Xplore databases were searched. A total of 303 articles were reviewed, 89 articles were read in-depth and 30 were included in the scoping review. The Substitution, Augmentation, Modification, Redefinition model was used to evaluate the value added by the technology integration. FINDINGS: Research on technology for self-management was conducted in 13 countries. Data analysis identified five kinds of platforms on which the systems were based, some systems were focused on a specific disease management processes, others were not. CONCLUSIONS: For individuals to effectively use systems to maintain maximum wellness, the systems must have a strong component of self-management and provide the user with meaningful information regarding their health states. RELEVANCE TO CLINICAL PRACTICE: Clinicians should choose systems for their clients based on the design, components and goals of the systems. PMID- 26990365 TI - Identification of the novel HLA-B*52:42 allele by polymerase chain reaction sequence-based typing in a Chinese bone marrow donor. AB - HLA-B*52:42 is different from HLA-B*52:01:01:01 by a single nucleotide substitution at position 343G>C. PMID- 26990366 TI - Remote ischemic conditioning protects against acetaminophen-induced acute liver injury in mice. AB - AIM: Acetaminophen (APAP) overdose is a major cause of drug-induced acute liver failure. Studies have shown that remote ischemic pre- and post-conditioning (R IPC and R-IPOST) can protect the liver against ischemia-reperfusion (I/R) and lipopolysaccharide-induced injuries. The aim of this study was to investigate the effect of R-IPC and R-IPOST on APAP-induced hepatotoxicity in mice. METHODS: Mice were randomized (n = 6 per group) to seven major groups: (i) normal control; (ii) sham operated; (iii) APAP; (iv) R-IPC + APAP; (v) R-IPC + APAP + zinc protoporphyrin (ZnPP); (vi) R-IPOST + APAP; and (vii) R-IPOST + APAP + ZnPP. Sixteen hours after APAP treatment, mouse liver and serum were collected to determine the severity of liver injury. RESULTS: The results showed that R-IPC and R-IPOST significantly decreased APAP-induced serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-alpha, interleukin-6, and hepatic malondialdehyde, as well as nitrotyrosine formation. Both R-IPC and R-IPOST could improve the hepatic superoxide dismutase, glutathione, and glutathione peroxidase activities and depress the expressions of pro-inflammatory associated proteins, such as inducible nitric oxide synthetase and nuclear factor-kappaB. They could also increase heme oxygenase-1 expression; however, ZnPP could counteract this protective effect. CONCLUSION: Remote ischemic conditioning has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting heme oxygenase-1 expression. PMID- 26990367 TI - Neutron Scattering of Aromatic and Aliphatic Liquids. AB - Organic solvents, such as cyclohexane, cyclohexene, methylcyclohexane, benzene and toluene, are widely used as both reagents and solvents in industrial processes. Despite the ubiquity of these liquids, the local structures that govern the chemical properties have not been studied extensively. Herein, we report neutron diffraction measurements on liquid cyclohexane, cyclohexene, methylcyclohexane, benzene and toluene at 298 K to obtain a detailed description of the local structure in these compounds. The radial distribution functions of the centres of the molecules, as well as the partial distribution functions for the double bond for cyclohexene and methyl group for methylcyclohexane and toluene have been calculated. Additionally, probability density functions and angular radial distribution functions were extracted to provide a full description of the local structure within the chosen liquids. Structural motifs are discussed and compared for all liquids, referring specifically to the functional group and aromaticity present in the different liquids. PMID- 26990368 TI - Inflammation related responses of intestinal cells to plum and cabbage digesta with differential carotenoid and polyphenol profiles following simulated gastrointestinal digestion. AB - SCOPE: Plums/cabbages represent fruits/vegetables rich in carotenoids and polyphenols, and have been associated with anti-inflammatory properties. METHODS AND RESULTS: We tested four plum (Italian Plum, Plum 620, Ersinger, and Cherry Plum) and cabbage varieties (Duchy, Kalorama, Kale, Scots Kale) with contrasting carotenoid/polyphenol content for their capability to alter inflammation/oxidative stress following simulated gastrointestinal digestion. Digesta were exposed to Caco-2(TC-7) and to a triple-culture(Caco-2/HT-29-MTX (90:10 v/v) including THP-1 like macrophages), stimulated to induce inflammation (10 MUg/mL LPS, 100 ng/mL TNF-alpha, 25 ng/mL IL-1-beta for 24 h, the last 18 h with digesta). Endpoints investigated included IL-6, IL-8, PGE-2, NO (all ELISA), NF-kappaB, MAPK, IL-6, IL-8, iNOS, Nrf2, COX-2 (real-time-PCR) and Nrf2 (immunostaining). IL-6 secretion was reduced in THP-1 cells by Scots Kale and Kalorama (up to 22%, p<0.05), and IL-8 secretion in the coculture (up to 35% in plums, p<0.05). This was accompanied by decreased NF-kB expressions in THP-1 cells (up to 30%, p<0.05). Nrf2 translocation to the nucleus was partly reduced by plums and cabbages (up to 40% (p<0.05). CONCLUSIONS: Some varieties, especially in the triple-culture, reduced inflammation, though this was unrelated to concentrations of carotenoids/polyphenols. The potential of phytochemical-rich fruits and vegetables to ameliorate gastrointestinal inflammation should be further investigated. PMID- 26990370 TI - Synthesis of Chiral 1,4-Benzodioxanes and Chromans by Enantioselective Palladium Catalyzed Alkene Aryloxyarylation Reactions. AB - A highly enantioselective alkene aryloxyarylation led to the high-yielding formation of a series of 1,4-benzodioxanes, 1,4-benzooxazines, and chromans containing quaternary stereocenters with excellent enantioselectivity. The sterically bulky and conformationally well defined chiral monophosphorus ligand L4 or L5 was responsible for the high reactivity and enantioselectivity of these transformations. The application of this method to the synthesis of the chiral chroman backbone of alpha-tocopherol was demonstrated. PMID- 26990369 TI - Evaluation of bacterial transmission to the paranasal sinuses through sinus irrigation. AB - BACKGROUND: Saline nasal irrigation is effective in the treatment of sinonasal disorders, including chronic rhinosinusitis (CRS). Despite bacterial contamination in rinse bottles and reports of infections from contaminated irrigation water, tap water is still used by ~50% of irrigation users, raising a potential public health concern. This study aimed to determine whether bacteria from the water supply used in sinus irrigations colonizes the paranasal sinuses. METHODS: Samples were taken from the: (1) water used for irrigation, (2) faucet or container the water originated from, (3) rinse bottle, and (4) postoperative ethmoid cavity from 13 subjects with CRS. Microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to assess similarity in microbiota between samples, and genomic analysis was performed to assess clonality of cultured bacteria. RESULTS: Of 13 subjects, 6 used distilled water, 6 used tap water, and 1 used well water in this institutional review board (IRB)-approved observational study. Well-water had markedly more bacteria than tap or distilled water. There was a trend toward tap having more bacteria than distilled water. The sinus samples were notably dissimilar to the bottle, faucet, and irrigant (M-H 0.15, 0.09, and 0.18, respectively). There was no difference in postoperative microbiotas between distilled and tap water users. CONCLUSION: The current study suggests that irrigation plays little role in establishing the sinus microbiome. Although rinsing with tap water may never be formally recommended, these data are useful to counsel patients who prefer to do so in non endemic areas if the municipal water supply is appropriately treated. PMID- 26990371 TI - Epithelial sheath neuroma: evidence supporting a hyperplastic etiology and epidermal origin. AB - An epithelial sheath neuroma (ESN) is a rare benign process of unknown pathogenesis, which is characterized histologically by multiple enlarged peripheral nerve fibers ensheathed by mature squamous epithelium. The histologic features can elicit concern for carcinomatous perineural invasion. The process is limited to the superficial dermis and is surrounded by a loose myxoid stroma, lymphocytic infiltrate and sometimes prominent infundibular cysts. The etiology of this peculiar entity has been debated and theories include a benign neoplasm, a hamartoma or an unusual reactive hyperplasia. There are only seven prior cases reported of ESN in the literature. Our case presented here is the first report to show connection of the ESN to the overlying epidermis and reactive epidermal hyperplasia. This suggests that ESN is indeed an unusual form of benign reactive hyperplasia. In addition, the clinical setting in this case was of pruritus and scratching in a background of papular urticaria, supporting the previous notion that ESN is probably a response to an external stimulus such as rubbing. PMID- 26990372 TI - A new virus discovered by immunocapture of double-stranded RNA, a rapid method for virus enrichment in metagenomic studies. AB - Next-generation sequencing technologies enable the rapid identification of viral infection of diseased organisms. However, despite a consistent decrease in sequencing costs, it is difficult to justify their use in large-scale surveys without a virus sequence enrichment technique. As the majority of plant viruses have an RNA genome, a common approach is to extract the double-stranded RNA (dsRNA) replicative form, to enrich the replicating virus genetic material over the host background. The traditional dsRNA extraction is time-consuming and labour-intensive. We present an alternative method to enrich dsRNA from plant extracts using anti-dsRNA monoclonal antibodies in a pull-down assay. The extracted dsRNA can be amplified by reverse transcriptase-polymerase chain reaction and sequenced by next-generation sequencing. In our study, we have selected three distinct plant hosts: Maori potato (Solanum tuberosum), rengarenga (Arthropodium cirratum) and broadleaved dock (Rumex obtusifolius) representing a cultivated crop, a New Zealand-native ornamental plant and a weed, respectively. Of the sequence data obtained, 31-74% of the reads were of viral origin, and we identified five viruses including Potato virus Y and Potato virus S in potato; Turnip mosaic virus in rengarenga (a new host record); and in the dock sample Cherry leaf roll virus and a novel virus belonging to the genus Macluravirus. We believe that this new assay represents a significant opportunity to upscale virus ecology studies from environmental, primary industry and/or medical samples. PMID- 26990373 TI - Length-Controlled Synthesis of Calcium Phosphate Nanorod and Nanowire and Application in Intracellular Protein Delivery. AB - Although calcium phosphate based nanomaterials are widely used in various biomedical application, the synthesis of high quality examples of such nanomaterials with controlled size and shape is challenging. Here, we report a single-phase approach for the length-controlled synthesis of calcium phosphate nanorods and nanowires of 2-5 nm diameter and 10-1000 nm length. The synthetic method involves the injection of tetrabutylammonium phosphate into an oleic acid solution of calcium oleate at 200-330 degrees C and controlling the nucleation growth kinetics of calcium phosphate by temperature, molar ratio of calcium to phosphate, reaction time, and solvent. Nanorods are formed at a calcium to phosphate molar ratio of 2:1, and with increasing temperature, more anisotropic nanowires are formed. As the reaction progresses at a certain growth condition, the length of the nanorods and nanowires increases with time and attains a maximum, and then the length distribution becomes broad. Thus, the best-quality nanomaterials are obtained by selecting the reaction temperature and then quenching the reaction at right time. These hydrophobic nanorods and nanowires are highly soluble, can be processed like conventional high-quality hydrophobic nanoparticles, and can be transformed into water-soluble functional nanoparticles via ligand-exchange or polymer-coating approaches. To demonstrate the application potential, we have transformed synthesized hydrophobic nanorods into water soluble nanorods via polymer coating and used them as carriers for the cellular delivery of protein. These nanorods and nanowires can be viewed as potential cellular delivery carriers. PMID- 26990374 TI - Does cigarette reduction while using nicotine replacement therapy prior to a quit attempt predict abstinence following quit date? AB - BACKGROUND AND AIMS: Previous studies have reported that people who use a smoking cessation medication while smoking and reduce cigarette consumption spontaneously are three times more likely to stop smoking after a quit date. The aim was to replicate this and assess whether it arises because of willed effortful reduction rather than unwilled reduced drive to smoke caused by medication. DESIGN: Secondary analysis of a trial where participants were randomised to smoke as normal or reduce by 75% over 2 weeks prior to quit date, using nicotine replacement therapy (NRT) in both arms. SETTING: Thirty-one UK primary care practices. PARTICIPANTS: A total of 517 adult smokers seeking quitting support in the carbon monoxide (CO) analyses and 421 in the cigarettes/day analyses. MEASUREMENTS: Russell Standard abstinence was recorded 4 weeks after quit date. The randomized groups were combined and the association between reduction and abstinence examined. The second analysis assessed whether this association differed by whether smokers were, or were not, instructed to reduce. FINDINGS: In all participants, there was no evidence that reducing cigarettes/day or CO by at least half compared with not reducing predicted abstinence at 4 weeks [risk ratio (RR) = 0.88; 95% confidence interval (CI) = 0.68-1.14 and RR = 1.20; 95% CI = 1.00-1.44, respectively]. However, in smokers instructed to reduce, CO reduction was associated with 4-week abstinence (RR = 1.52; 95% CI = 1.16-2.00), but not among people advised not to reduce (RR = 0.91; 95% CI = 0.67-1.24). CONCLUSIONS: Smoking reduction prior to a target quit date while on a smoking cessation medication may only predict subsequent abstinence when smokers are consciously attempting to reduce. PMID- 26990375 TI - Enterobius vermicularis and its role in paediatric appendicitis: protection or predisposition? AB - BACKGROUND: E nterobius vermicularis is one of the most common parasitic infections of the gastrointestinal tract, and has been shown to infest up to 28% of children worldwide. The role of E . vermicularis in acute appendicitis has previously been questioned, with some studies identifying infection as a precursor for inflammation of the appendix, with others refuting such a link. METHODS: A retrospective review was conducted of all appendices received for histological analysis at our unit from January 2002 to December 2011 (10-year period), removed in the course of acute appendicectomy in children aged 3 to 15 years. Appendices were categorized by degree of inflammation and infestation with E . vermicularis. RESULTS: Appendicectomy for clinical suspicion of acute appendicitis was performed in 2923 patients, 1694 (58%) male, median age 11.6 years. E . vermicularis was present in 4% of appendices; 25% of which showed concurrent acute inflammation. E . vermicularis infestation was more common in females (F : M 76% versus 24% of inflamed appendices and 66.7% versus 33.3% for non-inflamed appendices). European individuals showed higher representation in the E . vermicularis group than the total study population (79% versus 53% respectively). CONCLUSION: E . vermicularis was found to be more common in females and those of European descent. Seventy-seven percent of patients with E . vermicularis did not have concurrent acute inflammation of the appendix on histological examination. The question remains as to whether infestation is protective of inflammation or whether infestation causes appendiceal colic and subsequent appendicectomy of a non-inflamed appendix, thereby protective of the morbidity of acute appendicitis. PMID- 26990376 TI - Polymer Acceptor Based on B<-N Units with Enhanced Electron Mobility for Efficient All-Polymer Solar Cells. AB - We demonstrate that polymer electron acceptors with excellent all-polymer solar cell (all-PSC) device performance can be developed from polymer electron donors by using B<-N units. By alleviating the steric hindrance effect of the bulky pendant moieties on the conjugated polymers that contain B<-N units, the pi-pi stacking distance of polymer backbones is decreased and the electron mobility is consequently enhanced by nearly two orders of magnitude. As a result, the power conversion efficiency of all-PSCs with the polymer acting as the electron acceptor is greatly improved from 0.12 % to 5.04 %. This PCE value is comparable to that of the best all-PSCs with state-of-the-art polymer acceptors. PMID- 26990377 TI - Rare UNC13B variations and risk of schizophrenia: Whole-exome sequencing in a multiplex family and follow-up resequencing and a case-control study. AB - Rare genomic variations inherited in multiplex schizophrenia families are suggested to play a role in the genetic etiology of the disease. To identify rare variations with large effects on the risk of developing schizophrenia, we performed whole-exome sequencing (WES) in two affected and one unaffected individual of a multiplex family with 10 affected individuals. We also performed follow-up resequencing of the unc-13 homolog B (Caenorhabditis elegans) (UNC13B) gene, a potential risk gene identified by WES, in the multiplex family and undertook a case-control study to investigate association between UNC13B and schizophrenia. UNC13B coding regions (39 exons) from 15 individuals of the multiplex family and 111 affected offspring for whom parental DNA samples were available were resequenced. Rare missense UNC13B variations identified by resequencing were further tested for association with schizophrenia in two independent case-control populations comprising a total of 1,753 patients and 1,602 controls. A rare missense variation (V1525M) in UNC13B was identified by WES in the multiplex family; this variation was present in five of six affected individuals, but not in eight unaffected individuals or one individual of unknown disease status. Resequencing UNC13B coding regions identified five rare missense variations (T103M, M813T, P1349T, I1362T, and V1525M). In the case-control study, there was no significant association between rare missense UNC13B variations and schizophrenia, although single-variant meta-analysis indicated that M813T was nominally associated with schizophrenia. These results do not support a contribution of rare missense UNC13B variations to the genetic etiology of schizophrenia in the Japanese population. (c) 2016 Wiley Periodicals, Inc. PMID- 26990378 TI - Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide: a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study). AB - AIM: To evaluate the efficacy and safety of adding insulin degludec (IDeg) to treatment in patients with type 2 diabetes receiving liraglutide and metformin and qualifying for treatment intensification because of inadequate glycaemic control. METHODS: In this 26-week, double-blind trial, patients who still had inadequate glycaemic control after a 15-week run-in period with initiation and dose escalation of liraglutide to 1.8 mg in combination with metformin (>=1500 mg) were randomized to addition of once-daily IDeg ('IDeg add-on to liraglutide' arm; n = 174) or placebo ('placebo add-on to liraglutide' arm; n = 172), with dosing of both IDeg and placebo based on titration guidelines. RESULTS: At 26 weeks, the mean change in glycated haemoglobin level was greater in the IDeg add on to liraglutide arm (-1.04%) than in the placebo add-on to liraglutide arm ( 0.16%; p < 0.0001). Similarly, the mean fasting plasma glucose reduction was greater, and self-measured plasma glucose values were lower at all eight time points, with IDeg add-on versus placebo add-on (both p < 0.0001). At 26 weeks, the IDeg dose was 51 U (0.54 U/kg). During the run-in period with liraglutide, body weight decreased by ~3 kg in both groups. After 26 weeks, the mean change was +2.0 kg (IDeg add-on to liraglutide) and -1.3 kg (placebo add-on to liraglutide). Confirmed hypoglycaemia rates were low in both groups, although higher with IDeg than with placebo (0.57 vs. 0.12 episodes/patient-years of exposure; p = 0.0002). Nocturnal confirmed hypoglycaemia was infrequent in both groups, with no episodes of severe hypoglycaemia, and no marked differences in adverse events with either treatment approach. CONCLUSION: The addition of liraglutide and IDeg to patients sub-optimally treated with metformin and liraglutide and requiring treatment intensification was found to be effective and well-tolerated. PMID- 26990379 TI - The effect of colostrum ingestion during the first 24 hours of life on early postnatal development of piglet immune systems. AB - It has been suggested that colostrum is important not only for direct protection from pathogens but also for proper development of immune systems in piglets. In this study, we focused on the effect of colostrum ingestion during the first 24 h of life on early postnatal development of piglet immune systems. Thirty-six piglets from five litters were divided into colostrum-fed (CoF) and colostrum deprived (CoD) groups. The former group was allowed to suckle normally while formula milk was fed to the latter group during the first 24 h of life. At the weaning period, the concentrations of fecal immunoglobulin (Ig) A and plasma IgG as well as the number of blood leukocyte subsets were analyzed. Fecal IgA and plasma IgG concentrations in the CoF group were more than twice as high as those in the CoD group (P < 0.01). In addition, the number of blood B cells was significantly higher in the CoF group than that in the CoD group (P < 0.05). This study demonstrates that colostrum ingestion during the first 24 h plays a significant role in early postnatal development of both mucosal and systemic immunity of piglets. PMID- 26990380 TI - High-Throughput Mechanobiology Screening Platform Using Micro- and Nanotopography. AB - We herein demonstrate the first 96-well plate platform to screen effects of micro and nanotopographies on cell growth and proliferation. Existing high-throughput platforms test a limited number of factors and are not fully compatible with multiple types of testing and assays. This platform is compatible with high throughput liquid handling, high-resolution imaging, and all multiwell plate based instrumentation. We use the platform to screen for topographies and drug topography combinations that have short- and long-term effects on T cell activation and proliferation. We coated nanofabricated "trench-grid" surfaces with anti-CD3 and anti-CD28 antibodies to activate T cells and assayed for interleukin 2 (IL-2) cytokine production. IL-2 secretion was enhanced at 200 nm trench width and >2.3 MUm grating pitch; however, the secretion was suppressed at 100 nm width and <0.5 MUm pitch. The enhancement on 200 nm grid trench was further amplified with the addition of blebbistatin to reduce contractility. The 200 nm grid pattern was found to triple the number of T cells in long-term expansion, a result with direct clinical applicability in adoptive immunotherapy. PMID- 26990382 TI - Prehospital management and outcome of avalanche patients with out-of-hospital cardiac arrest: a retrospective study in Tyrol, Austria. AB - AIM: The aim of this study is to describe the prehospital management and outcome of avalanche patients with out-of-hospital cardiac arrest in Tyrol, Austria, for the first time since the introduction of international guidelines in 1996. PATIENTS AND METHODS: This study involved a retrospective analysis of all avalanche accidents involving out-of-hospital cardiac arrest between 1996 and 2009 in Tyrol, Austria. RESULTS: A total of 170 completely buried avalanche patients were included. Twenty-eight victims were declared dead at the scene. Of 34 patients with short burial, cardiopulmonary resuscitation (CPR) was performed in 27 (79%); 15 of these patients (56%) were transported to hospital with ongoing CPR and four patients were rewarmed with extracorporeal circulation; no patient survived. Of 108 patients with long burial, 49 patients had patent or unknown airway status; CPR was performed in 25 of these patients (51%) and 14 patients (29%) were transported to hospital. Four patients were rewarmed, but only one patient with witnessed cardiac arrest survived. Since the introduction of guidelines in 1996, there has been a marginally significant increase in the rate of documenting airway assessment, but no change in documenting the duration of burial or CPR. CONCLUSION: CPR is continued to hospital admission in patients with short burial and asphyxial cardiac arrest, but withheld or terminated at the scene in patients with long burial and possible hypothermic cardiac arrest. Insufficient transfer of information from the accident site to the hospital may partially explain the poor outcome of avalanche victims with out-of-hospital cardiac arrest treated with emergency cardiac care. PMID- 26990381 TI - Lipid Droplets Form from Distinct Regions of the Cell in the Fission Yeast Schizosaccharomyces pombe. AB - Eukaryotic cells store cholesterol/sterol esters (SEs) and triacylglycerols (TAGs) in lipid droplets, which form from the contiguous endoplasmic reticulum (ER) network. However, it is not known if droplets preferentially form from certain regions of the ER over others. Here, we used fission yeast Schizosaccharomyces pombe cells where the nuclear and cortical/peripheral ER domains are distinguishable by light microscopy to show that SE-enriched lipid droplets form away from the nucleus at the cell tips, whereas TAG-enriched lipid droplets form around the nucleus. Sterols localize to the regions of the cells where droplets enriched in SEs are observed. TAG droplet formation around the nucleus appears to be a strong function of diacylglycerol (DAG) homeostasis with Cpt1p, which coverts DAG into phosphatidylcholine and phosphatidylethanolamine localized exclusively to the nuclear ER. Also, Dgk1p, which converts DAG into phosphatidic acid localized strongly to the nuclear ER over the cortical/peripheral ER. We also show that TAG more readily translocates from the ER to lipid droplets than do SEs. The results augment the standard lipid droplet formation model, which has SEs and TAGs flowing into the same nascent lipid droplet regardless of its biogenesis point in the cell. PMID- 26990383 TI - Editorial Comment to Combination therapy with beta3 -adrenoceptor agonists and muscarinic acetylcholine receptor antagonists: Efficacy in rats with bladder overactivity. PMID- 26990384 TI - Clinical guideline for the treatment of dual pathology in the adult population. PMID- 26990385 TI - Psychiatric comorbidity in a sample of cocaine-dependent outpatients seen in the Community of Madrid drug addiction care network. AB - The objective of this study was to estimate the current prevalence of psychiatric disorders in cocaine-dependent patients who attend different treatment centres in the Community of Madrid. A prospective multicentre study was used, and a total of 197 cocaine-dependent subjects were assessed. The assessment instrument used for diagnosis was the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). The main findings of this study were a high prevalence of psychiatric comorbidity in cocaine-dependent patients seeking treatment (64.0%). The most common Non Substance Use Disorders found were attention deficit/hyperactivity Disorders (34.5%) and depressive disorders (13.7%). The most common Substance Use Disorder was alcohol dependence (28.4%). Cocaine dependent patients who had a depressive disorder and were alcohol dependent presented a more severe clinical profile and a higher degree of psychopathology, measured using different assessment tools, than the patients who were only cocaine dependent. These data suggest that the presence of psychiatric comorbidity could constitute a risk factor associated with the severity of cocaine dependence. The clinical heterogeneity found also indicates the need to search for individualised treatments that more specifically fit the needs of this population. PMID- 26990386 TI - Validity and Reliability of the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) in University Students. AB - The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), developed by the World Health Organization (WHO), has been used successfully in many countries, but there are few studies of its validity and reliability for the Mexican population. The objective of this study was to determine the psychometric properties of the self-administered ASSIST test in university students in Mexico. This was an ex post facto non-experimental study with 1,176 undergraduate students, the majority women (70.1%) aged 18-23 years (89.5%) and single (87.5%). To estimate concurrent validity, factor analysis and tests of reliability and correlation were carried out between the subscale for alcohol and AUDIT, those for tobacco and the Fagerstrom Test, and those for marijuana and DAST-20. Adequate reliability coefficients were obtained for ASSIST subscales for tobacco (alpha = 0.83), alcohol (alpha = 0.76), and marijuana (alpha = 0.73). Significant correlations were found only with the AUDIT (r = 0.71) and the alcohol subscale. The best balance of sensitivity and specificity of the alcohol subscale (83.8% and 80%, respectively) and the largest area under the ROC curve (81.9%) was found with a cutoff score of 8. The self-administered version of ASSIST is a valid screening instrument to identify at-risk cases due to substance use in this population. PMID- 26990387 TI - Video gamers of League of Legends: The role of passion in abusive use and in performance. AB - There is growing concern about the addictive potential of Massively Multiplayer Online Role Playing Games (MMORPG). The Multiplayer Online Battle Arena (MOBA) is a new genre, poorly studied but very popular, in which performance holds priority over immersion. The aim of the current study was to explore the influence of passion both on abuse and performance, using the dualistic model of passion. A total of 369 participants completed an online questionnaire that included problematic use and the Passion Scale. From players' nicknames, performance statistics were obtained. The results show that harmonious passion is a protector from negative consequences. On the other hand, obsessive passion predicts negative consequences and use of videogames for evasion. Obsessive passion also predicts better performance. These results suggest that distinguishing the two kinds of passion is important because they influence vulnerability to developing maladaptive behaviors and also players' performance. PMID- 26990388 TI - Alcohol-related expectancies in adults and adolescents: Similarities and disparities. AB - This study aimed to contrast student and not student outcome expectancies, and explore the diversity of alcohol-related cognitions within a wider student sample. Participants (n=549) were college students (higher education-typically aged 15-18 years), university students (further education-typically aged 18-22 years) and business people (white collar professionals <50 years) who completed questionnaires in their place of work or education. Overall positive expectancies were higher in the college students than in the business or university samples. However, not all expectancy subcategories followed this pattern. Participant groups of similar age were therefore alike in some aspects of their alcohol related cognitions but different in others. Similarly, participant groups whom are divergent in age appeared to be alike in some of their alcohol-related cognitions, such as tension reduction expectancies. Research often homogenises students as a specific sub-set of the population, this paper hi-lights that this may be an over-simplification. Furthermore, the largely exclusive focus on student groups within research in this area may also be an oversight, given the diversity of the findings demonstrated between these groups. PMID- 26990389 TI - Iudicium: An Educational Intervention for addressing Risk Perception of Alcohol Abuse in Adolescents. AB - Negative consequences of alcohol abuse during adolescence have been extensively described. Consequently, different interventions have been developed to address this issue. This article describes the implementation and evaluation of Iudicium, an educational drama-based intervention designed to increase risk perception of alcohol abuse. In this activity, high school students judge a case in which alcohol consumption had negative consequences (e.g., fights, unwanted pregnancy, and car accident). A trial is simulated and after that, a debriefing takes place during which the activity is discussed and informational materials on the effects of alcohol is provided and commented. A total of 318 students (55.7% females and 44.3% males) from five high schools participated in the study. Data regarding risk perception of alcohol abuse and adequacy of the activity was collected before and after the intervention. Results suggest that Iudicium was effective in increasing risk perception of abusive drinking, reaching a 34% of increase regarding risk perception. Participants highlighted the experiential component of Iudicium as a strength. The intervention was well-accepted, easy to understand and apparently an effective tool for increasing risk perception of alcohol abuse amongst high school students. PMID- 26990390 TI - Substance abuse and crime: considerations for a comprehensive forensic assessment. AB - There is a strong link between drug use and crime, but this relationship is complex. Drug use does not necessarily lead to an increase in crimes, such as theft, rape or assault, even among regular users or addicts. However, in cases of individuals who consume drugs excessively and commit crimes, both factors are linked. Poverty, personality disorders, social and cultural variables, relationships with other users and previous incarceration or drug use are all factors. These issues play an important role in understanding the risk of crime and drug use. Most addicts should be held liable for most criminal behaviour motivated by addiction, but that addiction can, in some cases, affect one's capacity for self-control over one's actions. This paper examines the current response of the Spanish Criminal Justice System to various aspects of drug abuse, focusing on court decisions related with the nature and enforcement of drug laws. It also addresses aspects of criminal responsibility for drug abuse and drug related crimes and suggests legislation on drugs, sentencing alternatives for drug offenses, and drug treatment options. Expert evidence plays a crucial role in this area in the court. PMID- 26990392 TI - The International Society of Biological and Environmental Repositories Presents Abstracts from Its Annual Meeting Breaking Down Walls: Unifying Biobanking Communities to Secure Our Sustainability April 5-8, 2016 Berlin, Germany. PMID- 26990391 TI - Objective Function and Learning Algorithm for the General Node Fault Situation. AB - Fault tolerance is one interesting property of artificial neural networks. However, the existing fault models are able to describe limited node fault situations only, such as stuck-at-zero and stuck-at-one. There is no general model that is able to describe a large class of node fault situations. This paper studies the performance of faulty radial basis function (RBF) networks for the general node fault situation. We first propose a general node fault model that is able to describe a large class of node fault situations, such as stuck-at-zero, stuck-at-one, and the stuck-at level being with arbitrary distribution. Afterward, we derive an expression to describe the performance of faulty RBF networks. An objective function is then identified from the formula. With the objective function, a training algorithm for the general node situation is developed. Finally, a mean prediction error (MPE) formula that is able to estimate the test set error of faulty networks is derived. The application of the MPE formula in the selection of basis width is elucidated. Simulation experiments are then performed to demonstrate the effectiveness of the proposed method. PMID- 26990393 TI - Prevalence and Quinolone Susceptibilities of Salmonella Isolated from the Feces of Preharvest Cattle Within Feedlots that Used a Fluoroquinolone to Treat Bovine Respiratory Disease. AB - Salmonella is an important foodborne pathogen and antimicrobial resistance can be a human health concern. The objectives of this cross-sectional study were to (1) determine the prevalence and quinolone susceptibility of Salmonella in feces of preharvest commercial feedlot cattle and (2) determine if the prevalence and susceptibility of Salmonella isolates were associated with previous fluoroquinolone use within pens. Five feedlots in western Kansas and Texas were selected based on their use of a commercially licensed fluoroquinolone for initial treatment of bovine respiratory disease (BRD). Twenty pen floor fecal samples were collected from each of 10 pens from each feedlot during early summer of 2012. Salmonella isolation was performed and microbroth dilution was used to determine susceptibility of isolates to nalidixic acid and ciprofloxacin. Prior antimicrobial treatment data were retrieved from feedlots' operational data. Generalized linear mixed models were used to assess associations between Salmonella prevalence and the number of fluoroquinolone treatments within pens while taking into consideration cattle demographic and management factors, as well as the hierarchical structure of the data. Overall, cumulative fecal prevalence of Salmonella was 38.0% (380/1000), but prevalence varied significantly (p < 0.01) among the five feedlots: 0.5% (1/200), 17.5% (35/200), 37.0% (74/200), 58.5% (117/200), and 76.5% (153/200). Salmonella serogroups included C1 (49.3%), E (36.4%), C2 (13.8%), and D (0.6%). There was no significant association (p = 0.52) between Salmonella prevalence and the frequency of fluoroquinolone treatments within a pen. All Salmonella isolates (n = 380) were susceptible to ciprofloxacin, while one isolate exceeded the human breakpoint (>=32 MUg/mL) for nalidixic acid. In conclusion, Salmonella fecal prevalence in preharvest cattle was highly variable among feedlots. Nearly all Salmonella isolates were susceptible to quinolones, despite the fact that a fluoroquinolone was used as the primary therapeutic antimicrobial to treat BRD in these feedlot populations. PMID- 26990394 TI - What are we missing? Risk behaviors among Arab-American adolescents and emerging adults. AB - BACKGROUND AND PURPOSE: Research on Arab-Americans as a distinct ethnic group is limited, especially when considering the health of Arab-American youth. This study describes health risk (substance use, violence); health promotive behaviors (hope, spirituality); and sexual activity (oral, vaginal, anal sex) of Arab American adolescents and emerging adults (aged 15-23) within their life context, as well as the association between these behaviors. METHODS: A secondary analysis of data on a subset of Arab-American participants obtained from a randomized control trial was utilized to conduct mixed methods analyses. Qualitative analyses completed on the open-ended questions used the constant comparative method for a subsample (n = 24) of participants. Descriptive quantitative analyses of survey data utilized bivariate analyses and stepwise logistic regression to explore the relation between risk behaviors and sexual activity among the full sample (n = 57). CONCLUSIONS: Qualitative analyses revealed two groups of participants: (a) multiple risk behaviors and negative life-events, and (b) minimal risk behaviors and positive life-events. Quantitative analyses indicated older youth, smokers, and those with higher hope pathways were more likely to report vaginal sex. IMPLICATIONS FOR PRACTICE: The unique cultural and social contexts of Arab-American youth provide a framework for recommendations for the prevention of risk behaviors. PMID- 26990395 TI - Phase and Size Control of Core-Shell Upconversion Nanocrystals Light up Deep Dual Luminescence Imaging and CT In Vivo. AB - Upconversion nanocrystals (UCNCs) have recently been explored as optical imaging nanoprobes. However, conventional beta-NaLuF4 (-) based UCNCs often suffer from large particle size and weak upconversion luminescence (UCL) intensity, leading to poor biocompatibility and low detection sensitivity. Here, a novel strategy for controlling the crystalline phase and size of UCNCs has been developed by doping of yttrium ions, resulting in particle size reduction and phase transition. The total UCL intensity of prepared core-shell UCNCs is significantly enhanced up to ~4.9 and ~17.4 times after Tm(3+) and Er(3+) doping than that of core UCNCs, offering deeper tissue UCL imaging with a depth of 8 mm in vivo. Moreover, the CT signal of core-shell UCNCs is ~1.5 and ~3.5 times brighter than that of core UCNCs and commercial ioversol agent because of increasing contents of Lu(3+) doped in UCNCs. The synthesized core-shell UCNCs hold a great promise in deep UCL and CT dual-modality imaging in vitro and in vivo. PMID- 26990396 TI - Ethanol production from lignocellulosic hydrolysates using engineered Saccharomyces cerevisiae harboring xylose isomerase-based pathway. AB - The efficient co-fermentation of glucose and xylose is necessary for the economically feasible bioethanol production from lignocellulosic biomass. Even with xylose utilizing Saccharomyces cerevisiae, the efficiency of the lignocellulosic ethanol production remains suboptimal mainly due to the low conversion yield of xylose to ethanol. In this study, we evaluated the co fermentation performances of SXA-R2P-E, a recently engineered isomerase-based xylose utilizing strain, in mixed sugars and in lignocellulosic hydrolysates. In a high-sugar fermentation with 70g/L of glucose and 40g/L of xylose, SXA-R2P-E produced 50g/L of ethanol with an yield of 0.43gethanol/gsugars at 72h. From dilute acid-pretreated hydrolysates of rice straw and hardwood (oak), the strain produced 18-21g/L of ethanol with among the highest yield of 0.43 0.46gethanol/gsugars ever reported. This study shows a highly promising potential of a xylose isomerase-expressing strain as an industrially relevant ethanol producer from lignocellulosic hydrolysates. PMID- 26990397 TI - Identifying inhibitory effects of lignocellulosic by-products on growth of lactic acid producing micro-organisms using a rapid small-scale screening method. AB - Sugars obtained from pretreated lignocellulose are interesting as substrate for the production of lactic acid in fermentation processes. However, by-products formed during pretreatment of lignocellulose can inhibit microbial growth. In this study, a small-scale rapid screening method was used to identify inhibitory effects of single and combined by-products on growth of lactic acid producing micro-organisms. The small-scale screening was performed in 48-well plates using 5 bacterial species and 12 by-products. Large differences were observed in inhibitory effects of by-products between different species. Predictions can be made for growth behaviour of different micro-organisms on acid pretreated or alkaline pretreated bagasse substrates using data from the small-scale screening. Both individual and combined inhibition effects were shown to be important parameters to predict growth. Synergy between coumaric acid, formic acid and acetic acid is a key inhibitory parameter in alkaline pretreated lignocellulose, while furfural is a key inhibitor in acid pretreated lignocellulose. PMID- 26990398 TI - Reuse of microalgae grown in full-scale wastewater treatment ponds: Thermochemical pretreatment and biogas production. AB - This study assessed thermochemical pretreatment of microalgae harvested from a full-scale wastewater treatment pond prior to its anaerobic digestion using acid and alkaline chemical doses combined with thermal pretreatment at 80 degrees C. Results indicated that alkaline and thermal pretreatment contributed mostly to glycoprotein and pectin solubilisation; whilst acid pretreatment solubilised mostly hemicellulose, with lower effectiveness for proteins. Regarding the anaerobic biodegradability, biochemical methane potential (BMP) tests showed that final methane yield was enhanced after almost all pretreatment conditions when compared to non-pretreated microalgae, with the highest increase for thermochemical pretreatment at the lowest dose (0.5%), i.e. 82% and 86% increase for alkaline and acid, respectively. At higher doses, salt toxicity was revealed by K(+) concentrations over 5000mg/L. All BMP data from pretreated biomass was successfully described by the modified Gompertz model and optimal condition (thermochemical 0.5% HCl) showed an increase in final methane yield and the process kinetics. PMID- 26990399 TI - Catalytic conversion of Chlorella pyrenoidosa to biofuels in supercritical alcohols over zeolites. AB - Microalgae have been considered as the feedstock for the third generation biofuels production, given its high lipid content and fast productivity. Herein, a catalytic approach for microalgae liquefaction to biocrude is examined in a temperature range of 250-300 degrees C in methanol and ethanol over zeolites. Higher biocrude yield was achieved in ethanol and at lower temperatures, while better quality biocrude with higher light biocrude ratio and lower average molecular weight (Mw) was favored in methanol and at higher temperatures. Application of zeolites improves the biocrude quality significantly. Among the catalysts, HY shows the strongest acidity and performs the best to produce high quality biocrude. Solid residues have been extensively explored with thermal gravity analysis and elemental analysis. It is reported for the first time that up to 99wt.% of sulfur is deposited in the solid residue at 250 degrees C for both solvents. PMID- 26990400 TI - Association between sedentary behavior time and waist-to-height ratio in preschool children. AB - OBJECTIVES: To explore the association between sedentary behavior time (SB), and waist-to-height ratio (WHtR) in preschool children. METHODS: This study included 646 preschool children (4- to 6-years old). WHtR was calculated as the ratio of waist/height with a cutoff of 0.5 used to define risk of abdominal obesity. Sedentary behavior was measured during 7 consecutive days by accelerometer. Logistic regression was used to determine the association between SB and WHtR. RESULTS: The prevalence of central obesity (WHtR) was 52.4 and 39.2% for girls and boys, respectively. Boys classified as being at risk for central obesity were more likely to spend more time in SB (OR: 1.6; CI: 1.1-2.5; P <= 0.05), adjusted by age (P <= 0.001). CONCLUSIONS: Our data suggested that boys classified as having higher SB were more likely to having more central obesity. Am. J. Hum. Biol. 28:746-748, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990401 TI - Kinetic Isotope Effect Provides Insight into the Vibrational Relaxation Mechanism of Aromatic Molecules: Application to Cyano-phenylalanine. AB - Varying the reduced mass of an oscillator via isotopic substitution provides a convenient means to alter its vibrational frequency and hence has found wide applications. Herein, we show that this method can also help delineate the vibrational relaxation mechanism, using four isotopomers of the unnatural amino acid p-cyano-phenylalanine (Phe-CN) as models. In water, the nitrile stretching frequencies of these isotopomers, Phe-(12)C(14)N (1), Phe-(12)C(15)N (2), Phe (13)C(14)N (3), and Phe-(13)C(15)N (4), are found to be equally separated by ~27 cm(-1), whereas their vibrational lifetimes are determined to be 4.0 +/- 0.2 (1), 2.2 +/- 0.1 (2), 3.4 +/- 0.2 (3), and 7.9 +/- 0.5 ps (4), respectively. We find that an empirical relationship that considers the effective reduced mass of CN can accurately account for the observed frequency gaps, while the vibrational lifetime distribution, which suggests an intramolecular relaxation mechanism, can be rationalized by the order-specific density of states near the CN stretching frequency. PMID- 26990402 TI - Validated Measures of Illness Perception and Behavior in People with Knee Pain and Knee Osteoarthritis: A Scoping Review. AB - OBJECTIVE: To identify validated measures that capture illness perception and behavior and have been used to assess people who have knee pain/osteoarthritis. METHODS: A scoping review was performed. Nine electronic databases were searched for records from inception through April 19, 2015. Search terms included illness perception, illness behavior, knee, pain, osteoarthritis, and their related terms. This review included English language publications of primary data on people with knee pain/osteoarthritis who were assessed with validated measures capturing any of 4 components of illness perception and behavior: monitor body, define and interpret symptoms, take remedial action, and utilize sources of help. Seventy-one publications included relevant measures. Two reviewers independently coded and analyzed each relevant measure within the 4 components. RESULTS: Sixteen measures were identified that capture components of illness perception and behavior in the target population. These measures were originally developed to capture constructs that include coping strategies/skills/styles, illness belief, illness perception, self-efficacy, and pain behavior. Coding results indicated that 5, 11, 12, and 5 of these measures included the monitor body, define and interpret symptoms, take remedial action, and utilize sources of help components, respectively. CONCLUSIONS: Several validated measures were interpreted as capturing some components, and only 1 measure was interpreted as capturing all of the components of illness perception and behavior in the target population. A measure that comprehensively captures illness perception and behavior could be valuable for informing and evaluating therapy for patients along a continuum of symptomatic knee osteoarthritis. PMID- 26990403 TI - Comparative analyses of light-induced anthocyanin accumulation and gene expression between the ray florets and leaves in chrysanthemum. AB - Light is one of the key environmental factors that affect anthocyanin biosynthesis. However, the underlying molecular mechanism remains unclear, and many problems regarding phenotypic change and corresponding gene regulation have not been solved. In the present study, comparative analyses of light-induced anthocyanin accumulation and gene expression between the ray florets and leaves were performed in Chrysanthemum * morifolium 'Purple Reagan'. After contrasting the variations in the flower color phenotype and relative pigment content, as well as expression patterns of structural and regulator genes responsible for anthocyanin biosynthesis and photoreceptor between different plant organs under light and dark conditions, we concluded that (1) both the capitulum and foliage are key organs responding to light for chrysanthemum coloration; (2) compared with flavones, shading makes a greater decrease on the anthocyanins accumulation; (3) most of the structural and regulatory genes in the light-induced anthocyanin pathway specifically express in the ray florets; and (4) CmCHS, CmF3H, CmF3'H, CmANS, CmDFR, Cm3GT, CmMYB5-1, CmMYB6, CmMYB7-1, CmbHLH24, CmCOP1 and CmHY5 are key genes for light-induced anthocyanin biosynthesis in chrysanthemum ray florets, while on the transcriptional level, the expressions of CmPHYA, CmPHYB, CmCRY1a, CmCRY1b and CmCRY2 are insignificantly changed. Moreover, the inferred comprehensive effect of multiple signals on the accumulation of anthocyanins and transmission channel of light signal that exist between the leaves and ray florets were further discussed. These results further our understanding of the relationship between the gene expression and light-induced anthocyanin biosynthesis, and lay foundations for the promotion of the molecular breeding of novel flower colors in chrysanthemums. PMID- 26990404 TI - Characterization of Arabidopsis thaliana FLAVONOL SYNTHASE 1 (FLS1) overexpression plants in response to abiotic stress. AB - Flavonoids are an important group of secondary metabolites that are involved in plant growth and contribute to human health. Many studies have focused on the biosynthesis pathway, biochemical characters, and biological functions of flavonoids. In this report, we showed that overexpression of FLS1 (FLS1-OX) not only altered seed coat color (resulting in a light brown color), but also affected flavonoid accumulation. Whereas fls1-3 mutants accumulated higher anthocyanin levels, FLS1-OX seedlings had lower levels than those of the wild type. Besides, shoot tissues of FLS1-OX plants exhibited lower flavonol levels than those of the wild-type. However, growth performance and abiotic stress tolerance of FLS1-OX, fls1-3, and wild-type plants were not significantly different. Taken together, FLS1 can be manipulated (i.e., silenced or overexpressed) to redirect the flavonoid biosynthetic pathway toward anthocyanin production without negative effects on plant growth and development. PMID- 26990405 TI - Inhibiting ethylene perception with 1-methylcyclopropene triggers molecular responses aimed to cope with cell toxicity and increased respiration in citrus fruits. AB - The ethylene perception inhibitor 1-methylcyclopropene (1-MCP) has been critical in understanding the hormone's mode of action. However, 1-MCP may trigger other processes that could vary the interpretation of results related until now to ethylene, which we aim to understand by using transcriptomic analysis. Transcriptomic changes in ethylene and 1-MCP-treated 'Navelate' (Citrus sinensis L. Osbeck) oranges were studied in parallel with changes in ethylene production, respiration and peel damage. The effects of compounds modifying the levels of the ethylene co-product cyanide and nitric oxide (NO) on fruit physiology were also studied. Results suggested that: 1) The ethylene treatment caused sub-lethal stress since it induced stress-related responses and reduced peel damage; 2) 1 MCP induced ethylene-dependent and ethylene-independent responsive networks; 3) 1 MCP triggered ethylene overproduction, stress-related responses and metabolic shifts aimed to cope with cell toxicity, which mostly affected to the inner part of the peel (albedo); 4) 1-MCP increased respiration and drove metabolism reconfiguration for favoring energy conservation but up-regulated genes related to lipid and protein degradation and triggered the over-expression of genes associated with the plasma membrane cellular component; 5) Xenobiotics and/or reactive oxygen species (ROS) might act as signals for defense responses in the ethylene-treated fruit, while their uncontrolled generation would induce processes mimicking cell death and damage in 1-MCP-treated fruit; 6) ROS, the ethylene co-product cyanide and NO may converge in the toxic effects of 1-MCP. PMID- 26990407 TI - A Neglected Case of Infective Pacing Wire Endocarditis. PMID- 26990408 TI - Trh (tdh-/trh+) gene analysis of clinical, environmental and food isolates of Vibrio parahaemolyticus as a tool for investigating pathogenicity. AB - Sequencing analysis of the trh gene encoding the TDH-related haemolysin of tdh /trh+ Vibrio parahaemolyticus isolated in Italy between 2002 and 2011 from clinical, environmental, and food samples revealed the presence of the trh2 variant in all isolates. The trh2 of the clinical isolate was 100% identical to other clinical tdh-/trh2 V. parahaemolyticus from Europe. Nucleotide and amino acid differences in the trh2 sequences of clinical isolates from Italy and other countries allowed a differentiation of the clinical strains from the majority of environmental or food strains isolated in Italy. Aspartic acid and isoleucine at positions 113 and 115, encoded by nucleotide triplets GAT and ATT at positions 337-339 and 343-345 of the complete trh gene sequence, were present in clinical strains from Europe (Italy, Norway and Germany), Asia and the United States. Only 35.5% of the tdh-/trh2 V. parahaemolyticus of environmental or food origin from Italy shared the same triplets/amino acid detected in clinical isolates, while 64.5% of isolates from the marine environment were different from those of clinical origins, demonstrating that differences occur amongst the trh2 sequences of strains from the environment and these polymorphisms may differentiate potentially pathogenic from less or non-pathogenic cultures found in the environment and seafood. In addition the distribution of T3SS2 genes was investigated in this group of tdh-/trh+ V. parahaemolyticus from different sources and in three clinical tdh+/trh- V. parahaemolyticus isolates. All tdh /trh+ V. parahaemolyticus of environmental or food source, independent of year of isolation or geographical origin, amplified all the screened T3SS2beta genes and tested negative to PCR assays for all five T3SS2alpha genes, as the tdh-/trh+ clinical V. parahaemolyticus isolate. The vopC genes, encoding for one of the effector proteins of T3SS2, were partially sequenced and compared to clinical tdh /trh+ and tdh+/trh+ V. parahaemolyticus isolates from other countries. Analysis of T3SS2beta vopC sequences revealed variation in tdh-/trh2 isolates from Italy, which were separated from a group of vopC sequences derived from trh2 V. parahaemolyticus from the USA. PMID- 26990406 TI - Preventive and chronic mineralocorticoid receptor antagonism is highly beneficial in obese SHHF rats. AB - BACKGROUND AND PURPOSE: Mineralocorticoid receptor (MR) activation contributes to heart failure (HF) progression. Its overactivity in obesity is thought to accelerate cardiac remodelling and HF development. Given that MR antagonists (MRA) are beneficial in chronic HF patients, we hypothesized that early MRA treatment may target obesity-related disorders and consequently delay the development of HF. EXPERIMENTAL APPROACH: Twenty spontaneously hypertensive HF dyslipidaemic obese SHHF(cp/cp) rats and 18 non-dyslipidaemic lean SHHF(+/+) controls underwent regular monitoring for their metabolic and cardiovascular phenotypes with or without MRA treatment [eplerenone (eple), 100 mg?kg(-1) ?day( 1) ] from 1.5 to 12.5 months of age. KEY RESULTS: Eleven months of eple treatment in obese rats (SHHF(cp/cp) eple) reduced the obesity-related metabolic disorders observed in untreated SHHF(cp/cp) rats by reducing weight gain, triglycerides and total cholesterol levels and by preserving adiponectinaemia. The MRA treatment predominantly preserved diastolic and systolic functions in obese rats by alleviating the eccentric cardiac hypertrophy observed in untreated SHHF(cp/cp) animals and preserving ejection fraction (70 +/- 1 vs. 59 +/- 1%). The MRA also improved survival independently of these pressure effects. CONCLUSION AND IMPLICATIONS: Early chronic eple treatment resulted in a delay in cardiac remodelling and HF onset in both SHHF(+/+) and SHHF(cp/cp) rats, whereas SHHF(cp/cp) rats further benefited from the MRA treatment through a reduction in their obesity and dyslipidaemia. These findings suggest that preventive MRA therapy may provide greater benefits in obese patients with additional risk factors of developing cardiovascular complications. PMID- 26990410 TI - Stereotactic Radiosurgery for Arteriovenous Malformations: The Effect of Treatment Period on Patient Outcomes. AB - BACKGROUND: Stereotactic radiosurgery (SRS) has been performed on patients with cerebral arteriovenous malformations (AVMs) for over 40 years. OBJECTIVE: To evaluate the impact of treatment period on obliteration, intracranial hemorrhage (ICH), and radiation-induced complications (RICs). METHODS: Retrospective comparison of 381 AVM patients having SRS during a 20-year period (group 1, January 1990 through March 1997, n = 160; group 2, April 1997 through December 2009, n = 221). The median radiological and clinical follow-up after initial SRS was 77 months and 93 months, respectively. RESULTS: Obliteration was 59.1% at 4 years and 85.1% at 8 years. Obliteration was more common in patients with hemispheric or cerebellar AVMs (P = .001), smaller prescription isodose volume (PIV) (P < .001), and group 1 patients (P < .001). The ICH rate was 7.7% at 4 years and 10.6% at 8 years. ICH was more common in older patients (P = .02), patients with deep AVM (P = .01), and larger PIV (P < .001). There was no difference in the ICH rate between the treatment groups (P = .18). The rate of permanent RICs was 4.4% at 4 years and 8.6% at 8 years. RICs were more common with larger PIVs (P < .001) and group 1 patients (P = .02). There was no difference in the number of patients having obliteration without new deficits between the 2 treatment periods (68.8% vs 73.3%, P = .33). CONCLUSION: Advances in SRS procedures over the past 20 years have resulted in a lower risk of RIC, but fewer patients had AVM obliteration. Increasing the prescription dose for patients with medium- and large-volume AVMs by using current conformal dose planning techniques may improve the obliteration rate while maintaining a low risk of RICs. PMID- 26990409 TI - Treatment of Basilar Invagination With Klippel-Feil Syndrome: Atlantoaxial Joint Distraction and Fixation With Transoral Atlantoaxial Reduction Plate. AB - BACKGROUND: Klippel-Feil syndrome (KFS) is characterized by congenital vertebral fusion of the cervical spine and a wide spectrum of associated anomalies. In patients with KFS with basilar invagination (BI), compression of the brainstem and upper cervical cord results in neurological deficits, and decompression and occipitocervical reconstruction are required. The highly varied anatomy of KFS makes a posterior occipitocervical fixation strategy challenging. For these patients, the transoral atlantoaxial reduction plate (TARP) operation is an optimal option to perform a direct anterior fixation to achieve stabilization. OBJECTIVE: To evaluate the effectiveness of TARP internal fixation for the treatment of BI with KFS. METHODS: Ten consecutive patients with BI and KFS who underwent TARP reduction and fixation from 2010 to 2012 were reviewed. Clinical assessment and image measurements were performed preoperatively and at the most recent follow-up. Nine patients (9/10) were followed for an average of 31.44 months. RESULTS: Symptoms were alleviated in 9 of 9 patients (100.00%). The odontoid process was ideally corrected with the TARP system. The mean clivus canal angle improved from 124 degrees preoperatively to 152 degrees postoperatively. The average preoperative and postoperative Japanese Orthopedic Association scores were 10.56 (n = 9) and 14.67 (n = 9), respectively, indicating 63.82% improvement. There was bony bridge catenation on the computed tomography scans and no evidence of hardware failure at 6 months. CONCLUSION: The TARP operation is effective and safe for treating patients with BI with KFS. The midterm clinical results were satisfactory. PMID- 26990412 TI - A near-infrared fluorescent aza-bodipy probe for dual-wavelength detection of hydrogen peroxide in living cells. AB - A boronic acid functionalized aza-borondipyrromethene dye (azaBDPBA) was applied to the dual-wavelength detection of hydrogen peroxide with high selectivity, which was loaded into cells to indicate the alteration of intracellular hydrogen peroxide during biological processes. PMID- 26990413 TI - A General Method for Aminoquinoline-Directed, Copper-Catalyzed sp(2) C-H Bond Amination. AB - An operationally simple and general method for copper-catalyzed, aminoquinoline assisted amination of beta-C(sp(2))-H bonds of benzoic acid derivatives is reported. The reaction employs Cu(OAc)2 or (CuOH)2CO3 catalysts, an amine coupling partner, and oxygen from air as a terminal oxidant. Exceptionally high generality with respect to amine coupling partners is observed. Specifically, primary and secondary aliphatic and aromatic amines, heterocycles, such as indoles, pyrazole, and carbazole, sulfonamides, as well as electron-deficient aromatic and heteroaromatic amines are competent coupling components. PMID- 26990414 TI - An evaluation of a three-component multiple schedule to indicate attention availability. AB - Students may engage in high rates of social approach responses at inappropriate times throughout the school day. One intervention that has been used to teach students appropriate and inappropriate times to access attention is a multiple schedule of reinforcement. In this study, we evaluated the efficacy of a multiple schedule that indicated when attention was available or not available in a bilingual preschool classroom during small-group instruction. Results showed that the intervention was effective in bringing students' social approaches under stimulus control. PMID- 26990415 TI - Know your neighbor: Microbiota and host epithelial cells interact locally to control intestinal function and physiology. AB - Interactions between the host and its associated microbiota differ spatially and the local cross talk determines organ function and physiology. Animals and their organs are not uniform but contain several functional and cellular compartments and gradients. In the intestinal tract, different parts of the gut carry out different functions, tissue structure varies accordingly, epithelial cells are differentially distributed and gradients exist for several physicochemical parameters such as nutrients, pH, or oxygen. Consequently, the microbiota composition also differs along the length of the gut, but also between lumen and mucosa of the same intestinal segment, and even along the crypt-villus axis in the epithelium. Thus, host-microbiota interactions are highly site-specific and the local cross talk determines intestinal function and physiology. Here we review recent advances in our understanding of site-specific host-microbiota interactions and discuss their functional relevance for host physiology. PMID- 26990416 TI - Assembling Color on the Nanoscale: Multichromatic Switchable Pixels from Plasmonic Atoms and Molecules. AB - Nanoparticles of different materials, shapes, and sizes are integrated into plasmonic atoms and molecules of defined shape and location through sequential directed self-assembly following a single patterning step. A rational tuning of the emitted color across the visible range of the electromagnetic spectrum and switchable polarization properties are demonstrated. Self-assembled plasmonic pixels provide tunable, stable, and switchable optical responses. PMID- 26990417 TI - Young Children Understand the Role of Agreement in Establishing Arbitrary Norms But Unanimity Is Key. AB - Human cultural groups value conformity to arbitrary norms (e.g., rituals, games) that are the result of collective "agreement." Ninety-six 3-year-olds had the opportunity to agree upon arbitrary norms with puppets. Results revealed that children normatively enforced these novel norms only on a deviator who had actually entered into the agreement (not on dissenting or ignorant individuals). Interestingly, any dissent during the norm-setting process (even if a majority of 90% preferred one course of action) prevented children from seeing a norm as established for anyone at all. These findings suggest that even young children understand something of the role of agreement in establishing mutually binding social norms, but that their notion of norm formation may be confined to conditions of unanimity. PMID- 26990418 TI - Bad Roots to Grow: Deficient Implicit Self-Evaluations in Chronic Depression With an Early Onset. AB - OBJECTIVE: Implicit self-esteem, which is based on associative learning processes, is considered to be constituted earlier in life than explicit, verbalized self-esteem. While depressed individuals report negative explicit self esteem, research has predominantly demonstrated equivalent levels of implicit self-esteem of depressed and healthy individuals. We further illuminate this finding by theorizing and empirically demonstrating that chronically depressed individuals show particularly low levels of implicit self-esteem when depression had an early onset. METHOD: We applied measures of implicit (name-letter test) and explicit (Rosenberg Self-Esteem Scale) self-esteem in chronically depressed patients with an early onset (N = 17), a late onset (N = 13), and an episodic depression (N = 29). RESULTS: As expected, patients with an early onset showed lower implicit self-esteem than the 2 other groups. CONCLUSION: Implicit self esteem may function as a marker of how deeply negative self-views are internalized. Furthermore, the distinction between early and late onset of chronic depression seems to be valuable for classification and potentially treatment of unipolar depression. PMID- 26990419 TI - The role of sphingolipids in neuronal plasticity of the brain. AB - This Editorial highlights a study by Muller et al. in which the authors suggest a new sphingolipid-dependent mechanism for behavioral extinction. Their study should be considered in the broad perspective of sphingolipid metabolic pathways and traffic (depicted in the graphic). Read the highlighted article 'A sphingolipid mechanism for behavioral extinction' on page 589. PMID- 26990421 TI - Muscle contracture diagnosis: the role of sonoelastography. AB - BACKGROUND: Sonoelastography plays today a major role in musculoskeletal disease, showing minor muscle injuries not well appreciable in conventional B-mode ultrasonography and integrating it in major muscle injuries diagnosis. The aim of this study was to demonstrate the ability of elastosonography in the diagnosis of muscular contracture in football players presenting negative basic echography. METHODS: We examined twenty-two football players using basic echography and elastosonography approximately 24-48 hours after the traumatic event and we subsequently re-evaluated them after two weeks. RESULTS: Conventional echography showed, in the early stage, no muscle injuries; in twenty-two out of twenty-two patients, sonoelastography had instead underlined a heterogeneous colorimetric map, related to decreased elasticity in the area of the muscle contracture. An evaluation effected 1-2 weeks later showed a clear improvement of the sonoelastographic appearance. CONCLUSIONS: This information will be useful for prognostication, post-traumatic monitoring and to detect subclinical changes in MIs even before there are changes on the routine B-mode ultrasound. PMID- 26990420 TI - Suppression of EC-SOD by oxLDL During Vascular Smooth Muscle Cell Proliferation. AB - Reactive oxygen species (ROS) produced by endothelial cells and macrophages play important roles in atherogenesis because they promote the formation of oxidized low-density lipoproteins (oxLDL). Extracellular-superoxide dismutase (EC-SOD) is mainly produced by vascular smooth muscle cells (VSMCs), is secreted into the extracellular space, and protects cells from the damaging effects of the superoxide anion. Thus, the expression of EC-SOD in VSMCs is crucial for protecting cells against atherogenesis; however, oxLDL-induced changes in the expression of EC-SOD in VSMCs have not yet been examined. We herein showed that oxLDL decreased EC-SOD mRNA and protein levels by binding to lectin-like oxidized LDL receptor-1 (LOX-1). Moreover, we demonstrated the significant role of mitogen activated protein kinase (MEK)/extracellular-regulated protein kinase (ERK) signaling in oxLDL-elicited reductions in the expression of EC-SOD and proliferation of VSMCs. The results obtained with the FCS treatment indicate that oxLDL-elicited reductions in the expression of EC-SOD are related to the proliferation of VSMCs. We herein showed for the first time that luteolin, a natural product, restored oxLDL-induced decreases in the expression of EC-SOD and proliferation of VSMCs. Collectively, the results of the present study suggest that oxLDL accelerates the development of atherosclerosis by suppressing the expression of EC-SOD and also that luteolin has potential as a treatment for atherosclerosis. J. Cell. Biochem. 117: 2496-2505, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990422 TI - Energetics demands and physiological responses to boxing match and subsequent recovery. AB - BACKGROUND: Determining the physiological profile of athletes in boxing match is important for defining aspects of physical performance that are important to competitive performance. Therefore, examination of the energy pathway of high level boxers' athletes can be very helpful for optimizing training and then improving boxing physical fitness and performance. The aim of the present study was to assess the physiological and cardiovascular responses during boxing matches and subsequent recovery. METHODS: Fifteen male international level boxers (mean age 19.56+/-3.6 years; mean body mass 72.46+/-11.86 kg; mean height 176.50+/-7.22 cm) participated in this study. Blood samples were drawn from the antecubital vein before and after the boxing matches (T1: pre-match rest measure around 11:00 a.m., T2: measure at 3 minutes of post-match recovery; T3: measure at 60 minutes of recovery; T4: measure at 24 hours post-match - the match started around 11:30 a.m.). An analysis of glucose, triglycerides, lactate, cholesterol, creatinine, uric-acid, high density lipoprotein, and low density lipoprotein concentrations was performed for each sample. Participants did perform a maximal incremental test to measure maximal heart rate (HRmax). Heart rate responses to the matches were measured and expressed in percentage of HRmax. RESULTS: The average HR recorded during the match corresponded to 93+/-3.26% of HRmax. The levels of glucose, lactate, and cholesterol increased significantly from T1 to T2. Likewise, creatinine levels increased significantly from T1 to T2 and T3. However, the cholesterol level decreased significantly at T3 in comparison with T1. Moreover, 24-hour post-match creatinine levels were significantly lower and triglyceride levels were significantly higher compared with T1. CONCLUSIONS: The main results of this study revealed that the boxing matches stress the lipid metabolism system during boxing and post-match (for at least 24 hours) even if it is widely recognized boxing being mainly composed of repeated short-duration anaerobic efforts. PMID- 26990423 TI - Iatrogenic delusional infestation: an observational study. PMID- 26990424 TI - Nicotine regulates cocaine-amphetamine-Regulated Transcript (Cart) in the mesocorticolimbic system. AB - Cocaine-and-Amphetamine Regulated Transcript (CART) mRNA and peptides are intensely expressed in the brain regions comprising mesocorticolimbic system. Studies suggest that CART peptides may have a role in the regulation of reward circuitry. The present study aimed to examine the effect of nicotine on CART expression in the mesocorticolimbic system. Three different doses of nicotine (0.2, 0.4, 0.6 mg/kg free base) were injected subcutaneously for 5 days, and on day 6, rats were decapitated following a challenge dose. CART mRNA and peptide levels in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (DST), amygdala (AMG), lateral hypothalamic area (LHA), and ventral tegmental area (VTA) were measured by quantitative real-time PCR (qPCR) and Western Blot analysis, respectively. In the mPFC, 0.4 and 0.6 mg/kg nicotine, decreased CART peptide levels whereas there was no effect on CART mRNA levels. In the VTA, a down-regulation of CART peptide expression was observed with 0.2 and 0.6 mg/kg nicotine. Conversely, 0.4 and 0.6 mg/kg nicotine increased CART mRNA levels in the AMG without affecting the CART peptide expression. Nicotine did not regulate CART mRNA or CART peptide expression in the NAc, DST, and LHA. We conclude that nicotine regulates CART expression in the mesocorticolimbic system and this regulation may play an important role in nicotine reward. Synapse 70:283 292, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990425 TI - Human Embryonic Stem Cell Lines with Lesions in FOXP3 and NF1. AB - Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of blastocyst staged embryos. Spare blastocyst staged embryos were obtained by in vitro fertilization (IVF) and donated for research purposes. hESCs carrying specific mutations can be used as a powerful cell system in modeling human genetic disorders. We obtained preimplantation genetic diagnosed (PGD) blastocyst staged embryos with genetic mutations that cause human disorders and derived hESCs from these embryos. We applied laser assisted micromanipulation to isolate the inner cell mass from the blastocysts and plated the ICM onto the mouse embryonic fibroblast cells. Two hESC lines with lesions in FOXP3 and NF1 were established. Both lines maintain a typical undifferentiated hESCs phenotype and present a normal karyotype. The two lines express a panel of pluripotency markers and have the potential to differentiate to the three germ layers in vitro and in vivo. The hESC lines with lesions in FOXP3 and NF1 are available for the scientific community and may serve as an important resource for research into these disease states. PMID- 26990426 TI - Association of Catalase and Glutathione Peroxidase 1 Polymorphisms with Chronic Hepatitis C Outcome. AB - The hepatic damage caused by hepatitis C virus (HCV) infection is associated with the host immune response and viral regulatory factors. Catalase (CAT) and glutathione peroxidase 1 (GPX1) are antioxidant enzymes located in the peroxisomes and mitochondria, respectively, and are responsible for the control of intracellular hydrogen peroxide levels. Polymorphisms in CAT (C-262T) and GPX1 (Pro198Leu) are correlated with serum levels and enzyme activity. This study aimed to investigate the association of genetic polymorphisms of CAT C-262T (rs1001179) and GPX1 Pro198Leu (rs1050450) with different stages of liver fibrosis and development of hepatocellular carcinoma (HCC). This study included 445 patients with chronic hepatitis C, of whom 139 patients had mild fibrosis (F0 F1), 200 had moderate/severe fibrosis (F2-F4), and 106 had HCC. Genotyping of SNPs was performed by real-time PCR using TaqMan probes. The Pro/Pro genotype of GPX1 was significantly associated with fibrosis severity, HCC, Child Pugh score, and BCLC staging. Additionally, patients carrying both CT+TT genotypes in the CAT gene and the Pro/Pro genotype in the GPX1 gene had higher risk for developing moderate/severe fibrosis or HCC (p = 0.009, OR 2.40 and p = 0.002, OR 3.56, respectively). CAT and GPX1 polymorphisms may be implicated in the severity of liver fibrosis and HCC caused by HCV. PMID- 26990428 TI - Development and validation of a method to determine thiabendazole and o phenylphenol in wastewater using micellar liquid chromatography-fluorescence detection. AB - A micellar liquid chromatographic method to determine thiabendazole (TBZ) and o phenylphenol in wastewater is described here. The sample was directly injected without any additional treatment other filtration. The pesticides were resolved in <11 min, using a mobile phase of 0.10 M SDS-6% 1-pentanol buffered at pH 3 running through a C18 column at 1 mL/min. The detection was performed by fluorescence at 305/360 and 245/345 nm excitation/emission wavelengths for TBZ and o-phenylphenol, respectively. The method was validated following the directives of the Validation and Peer Review of U.S. Environmental Protection Agency Chemical Methods of Analysis guidelines in terms of selectivity, quantitation range (0.01-0.02 to 2 mg/L), detection limit (0.005-0.008 mg/L), trueness (92.1-104.2%), precision (<13.9%), robustness (<6.6%), and stability under storage conditions. The procedure was applied to the screening of TBZ and o phenylphenol in wastewater samples from citrus packing plants, agricultural gutters, urban sewage, as well as in influent and effluent wastewater treatment plants. PMID- 26990427 TI - The Impact of Liver Cell Injury on Health-Related Quality of Life in Patients with Chronic Liver Disease. AB - BACKGROUND: Patients with chronic liver disease often suffer from unspecific symptoms and report severe impairment in the quality of life. The underlying mechanisms are multifactorial and include disease-specific but also liver related causes. The current analysis evaluated the association of hepatocellular apoptosis in non-viral chronic liver disease and health-related quality of life (HRQL). Furthermore we examined factors, which influence patient's physical and mental well-being. METHODS: A total of 150 patients with non-infectious chronic liver disease were included between January 2014 and June 2015. The German version of the Chronic Liver Disease Questionnaire (CLDQ-D), a liver disease specific instrument to assess HRQL, was employed. Hepatocellular apoptosis was determined by measuring Cytokeratin 18 (CK18, M30 Apoptosense ELISA). RESULTS: Female gender (5.24 vs. 5.54, p = 0.04), diabetes mellitus type II (4.75 vs. 5.46, p<0.001) and daily drug intake (5.24 vs. 6.01, p = 0.003) were associated with a significant impairment in HRQL. HRQL was not significantly different between the examined liver diseases. Levels of CK18 were the highest in patients with NASH compared to all other disease entities (p<0.001). Interestingly, CK18 exhibited significant correlations with obesity (p<0.001) and hyperlipidemia (p<0.001). In patients with cirrhosis levels of CK18 correlated with the MELD score (r = 0.18, p = 0.03) and were significantly higher compared to patients without existing cirrhosis (265.5 U/l vs. 186.9U/l, p = 0.047). Additionally, CK18 showed a significant correlation with the presence and the degree of hepatic fibrosis (p = 0.003) and inflammation (p<0.001) in liver histology. Finally, there was a small negative association between CLDQ and CK18 (r = -0.16, p = 0.048). CONCLUSION: Different parameters are influencing HRQL and CK18 levels in chronic non-viral liver disease and the amount of hepatocellular apoptosis correlates with the impairment in HRQL in chronic non-viral liver diseases. These findings support the role of liver-protective therapies for the improvement of the quality of life in chronic liver disease. PMID- 26990429 TI - Comparing Emergency Intubation with Direct and Video Laryngoscopy. PMID- 26990430 TI - Deletion of FGFR3 in Osteoclast Lineage Cells Results in Increased Bone Mass in Mice by Inhibiting Osteoclastic Bone Resorption. AB - Fibroblast growth factor receptor 3 (FGFR3) participates in bone remodeling. Both Fgfr3 global knockout and activated mice showed decreased bone mass with increased osteoclast formation or bone resorption activity. To clarify the direct effect of FGFR3 on osteoclasts, we specifically deleted Fgfr3 in osteoclast lineage cells. Adult mice with Fgfr3 deficiency in osteoclast lineage cells (mutant [MUT]) showed increased bone mass. In a drilled-hole defect model, the bone remodeling of the holed area in cortical bone was also impaired with delayed resorption of residual woven bone in MUT mice. In vitro assay demonstrated that there was no significant difference between the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts derived from wild-type and Fgfr3 deficient bone marrow monocytes, suggesting that FGFR3 had no remarkable effect on osteoclast formation. The bone resorption activity of Fgfr3-deficient osteoclasts was markedly decreased accompanying with downregulated expressions of Trap, Ctsk, and Mmp 9. The upregulated activity of osteoclastic bone resorption by FGF2 in vitro was also impaired in Fgfr3-deficient osteoclasts, indicating that FGFR3 may participate in the regulation of bone resorption activity of osteoclasts by FGF2. Reduced adhesion but not migration in osteoclasts with Fgfr3 deficiency may be responsible for the impaired bone resorption activity. Our study for the first time genetically shows the direct positive regulation of FGFR3 on osteoclastic bone resorption. (c) 2016 American Society for Bone and Mineral Research. PMID- 26990432 TI - Genetic variation in target-site resistance to pyrethroids and pirimicarb in Tunisian populations of the peach potato aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). AB - BACKGROUND: We used molecular assays to diagnose resistance to pyrethroids and pirimicarb in samples of Myzus persicae from field crops or an insect suction trap in Tunisia. Genotypes for resistance loci were related to ones for polymorphic microsatellite loci in order to investigate breeding systems and patterns of genetic diversity, and to inform resistance management tactics. RESULTS: The kdr mutation L1014F conferring pyrethroid resistance was found in all samples. The M918T s-kdr mutation also occurred in most samples, but only in conjunction with kdr. We discovered a previously unreported genotype heterozygous for L1014F but homozygous for M918T. Samples with modified acetylcholinesterase (MACE) conferring resistance to pirimicarb were less common but widespread. 16% of samples contained both the kdr and MACE mutations. Many unique microsatellite genotypes were found, suggesting that M. persicae is holocyclic in Tunisia. There were no consistent associations between resistance and microsatellite markers. CONCLUSION: This first study of insecticide resistance in M. persicae in North Africa showed genetic variation in insecticide resistance within microsatellite multilocus genotypes (MLGM s) and the same resistance mechanisms to be present in different MLGM s. This contrasts with variation in northern Europe where M. persicae is fully anholocyclic. Implications for selection and control strategies are discussed. (c) 2016 Society of Chemical Industry. PMID- 26990431 TI - Allometry and Scaling of the Intraocular Pressure and Aqueous Humour Flow Rate in Vertebrate Eyes. AB - In vertebrates, intraocular pressure (IOP) is required to maintain the eye into a shape allowing it to function as an optical instrument. It is sustained by the balance between the production of aqueous humour by the ciliary body and the resistance to its outflow from the eye. Dysregulation of the IOP is often pathological to vision. High IOP may lead to glaucoma, which is in man the second most prevalent cause of blindness. Here, we examine the importance of the IOP and rate of formation of aqueous humour in the development of vertebrate eyes by performing allometric and scaling analyses of the forces acting on the eye during head movement and the energy demands of the cornea, and testing the predictions of the models against a list of measurements in vertebrates collated through a systematic review. We show that the IOP has a weak dependence on body mass, and that in order to maintain the focal length of the eye, it needs to be an order of magnitude greater than the pressure drop across the eye resulting from gravity or head movement. This constitutes an evolutionary constraint that is common to all vertebrates. In animals with cornea-based optics, this constraint also represents a condition to maintain visual acuity. Estimated IOPs were found to increase with the evolution of terrestrial animals. The rate of formation of aqueous humour was found to be adjusted to the metabolic requirements of the cornea, scaling as Vac(0.67), where Vac is the volume of the anterior chamber. The present work highlights an interdependence between IOP and aqueous flow rate crucial to ocular function that must be considered to understand the evolution of the dioptric apparatus. It should also be taken into consideration in the prevention and treatment of glaucoma. PMID- 26990433 TI - STAT4-mediated transcriptional repression of the IL5 gene in human memory Th2 cells. AB - Type I interferon (IFN-alpha/beta) plays a critical role in suppressing viral replication by driving the transcription of hundreds of interferon-sensitive genes (ISGs). While many ISGs are transcriptionally activated by the ISGF3 complex, the significance of other signaling intermediates in IFN-alpha/beta mediated gene regulation remains elusive, particularly in rare cases of gene silencing. In human Th2 cells, IFN-alpha/beta signaling suppressed IL5 and IL13 mRNA expression during recall responses to T-cell receptor (TCR) activation. This suppression occurred through a rapid reduction in the rate of nascent transcription, independent of de novo expression of ISGs. Further, IFN-alpha/beta mediated STAT4 activation was required for repressing the human IL5 gene, and disrupting STAT4 dimerization reversed this effect. This is the first demonstration of STAT4 acting as a transcriptional repressor in response to IFN alpha/beta signaling and highlights the unique activity of this cytokine to acutely block the expression of an inflammatory cytokine in human T cells. PMID- 26990434 TI - Functional study of TGM1 missense mutations in autosomal recessive congenital ichthyosis. PMID- 26990435 TI - Photodynamic Effect of Ni Nanotubes on an HeLa Cell Line. AB - Nickel nanomaterials are promising in the biomedical field, especially in cancer diagnostics and targeted therapy, due to their distinctive chemical and physical properties. In this experiment, the toxicity of nickel nanotubes (Ni NTs) were tested in an in vitro cervical cancer model (HeLa cell line) to optimize the parameters of photodynamic therapy (PDT) for their greatest effectiveness. Ni NTs were synthesized by electrodeposition. Morphological analysis and magnetic behavior were examined using a Scanning electron microscope (SEM), an energy dispersive X-ray analysis (EDAX) and a vibrating sample magnetometer (VSM) analysis. Phototoxic and cytotoxic effects of nanomaterials were studied using the Ni NTs alone as well as in conjugation with aminolevulinic acid (5-ALA); this was performed both in the dark and under laser exposure. Toxic effects on the HeLa cell model were evaluated by a neutral red assay (NRA) and by detection of intracellular reactive oxygen species (ROS) production. Furthermore, 10-200 nM of Ni NTs was prepared in solution form and applied to HeLa cells in 96-well plates. Maximum toxicity of Ni NTs complexed with 5-ALA was observed at 100 J/cm2 and 200 nM. Up to 65-68% loss in cell viability was observed. Statistical analysis was performed on the experimental results to confirm the worth and clarity of results, with p-values = 0.003 and 0.000, respectively. Current results pave the way for a more rational strategy to overcome the problem of drug bioavailability in nanoparticulate targeted cancer therapy, which plays a dynamic role in clinical practice. PMID- 26990436 TI - 25 Years of Human Mutation. PMID- 26990437 TI - Dibenzo[def,p]chrysene transplacental carcinogenesis in wild-type, Cyp1b1 knockout, and CYP1B1 humanized mice. AB - The cytochrome P450 (CYP) 1 family is active toward numerous environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs). Utilizing a mouse model, null for Cyp1b1 and expressing human CYP1B1, we tested the hypothesis that hCYP1B1 is important for dibenzo[def,p]chrysene (DBC) transplacental carcinogenesis. Wild-type mCyp1b1, transgenic hCYP1B1 (mCyp1b1 null background), and mCyp1b1 null mice were assessed. Each litter had an equal number of siblings with Ahrb-1/d and Ahrd/d alleles. Pregnant mice were dosed (gavage) on gestation day 17 with 6.5 or 12 mg/kg of DBC or corn oil. At 10 months of age, mortality, general health, lymphoid disease and lung tumor incidence, and multiplicity were assessed. hCYP1B1 genotype did not impact lung tumor multiplicity, but tended to enhance incidence compared to Cyp1b1 wild-type mice (P = 0.07). As with Cyp1b1 in wild-type mice, constitutive hCYP1B1 protein is non-detectable in liver but was induced with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Wild-type mice were 59% more likely to succumb to T-cell Acute Lymphoblastic Leukemia (T-ALL). Unlike an earlier examination of the Ahr genotype in this model (Yu et al., Cancer Res, 2006;66:755-762), but in agreement with a more recent study (Shorey et al., Toxicol Appl Pharmacol, 2013;270:60-69), this genotype was not associated with lung tumor incidence, multiplicity, or mortality. Sex was not significant with respect to lung tumor incidence or mortality but males exhibited significantly greater multiplicity. Lung tumor incidence was greater in mCyp1b1 nulls compared to wild-type mice. To our knowledge, this is the first application of a humanized mouse model in transplacental carcinogenesis. (c) 2016 Wiley Periodicals, Inc. PMID- 26990440 TI - Expiratory and sympathetic long-term facilitation and their interactions after acute intermittent hypoxia (AIH). PMID- 26990439 TI - Has Interprofessional Education Changed Learning Preferences? A National Perspective. AB - OBJECTIVE: To assess how changes in curriculum, accreditation standards, and certification and licensure competencies impacted how medical students and physician residents value interprofessional team and patient-centered care. PRIMARY DATA SOURCE: The Department of Veterans Affairs Learners' Perceptions Survey (2003-2013). The nationally administered survey asked a representative sample of 56,569 U.S. medical students and physician residents, with a comparison group of 78,038 nonphysician trainees, to rate satisfaction with 28 elements, in two overall domains, describing their clinical learning experiences at VA medical centers. STUDY DESIGN: Value preferences were scored as independent adjusted associations between an element (interprofessional team, patient-centered preceptor) and the respective overall domain (clinical learning environment, faculty, and preceptors) relative to a referent element (quality of clinical care, quality of preceptor). PRINCIPAL FINDINGS: Physician trainees valued interprofessional (14 percent vs. 37 percent, p < .001) and patient-centered learning (21 percent vs. 36 percent, p < .001) less than their nonphysician counterparts. Physician preferences for interprofessional learning showed modest increases over time (2.5 percent/year, p < .001), driven mostly by internal medicine and surgery residents. Preferences did not increase with trainees' academic progress. CONCLUSIONS: Despite changes in medical education, physician trainees continue to lag behind their nonphysician counterparts in valuing experience with interprofessional team and patient-centered care. PMID- 26990438 TI - The Transcript Profile of a Traditional Chinese Medicine, Atractylodes lancea, Revealing Its Sesquiterpenoid Biosynthesis of the Major Active Components. AB - Atractylodes lancea (Thunb.) DC., named "Cangzhu" in China, which belongs to the Asteraceae family. In some countries of Southeast Asia (China, Thailand, Korea, Japan etc.) its rhizome, commonly called rhizoma atractylodis, is used to treat many diseases as it contains a variety of sesquiterpenoids and other components of medicinal importance. Despite its medicinal value, the information of the sesquiterpenoid biosynthesis is largely unknown. In this study, we investigated the transcriptome analysis of different tissues of non-model plant A. lancea by using short read sequencing technology (Illumina). We found 62,352 high quality unigenes with an average sequence length of 913 bp in the transcripts of A. Lancea. Among these, 43,049 (69.04%), 30,264 (48.53%), 26,233 (42.07%), 17,881 (28.67%) and 29,057(46.60%) unigenes showed significant similarity (E-value<1e( 5)) to known proteins in Nr, KEGG, SWISS-PROT, GO, and COG databases, respectively. Of the total 62,352 unigenes, 43,049 (Nr Database) open reading frames were predicted. On the basis of different bioinformatics tools we identify all the enzymes that take part in the terpenoid biosynthesis as well as five different known sesquiterpenoids via cytosolic mevalonic acid (MVA) pathway and plastidal methylerythritol phosphate (MEP) pathways. In our study, 6, 864 Simple Sequence Repeats (SSRs) were also found as great potential markers in A. lancea. This transcriptomic resource of A. lancea provides a great contribution in advancement of research for this specific medicinal plant and more specifically for the gene mining of different classes of terpenoids and other chemical compounds that have medicinal as well as economic importance. PMID- 26990442 TI - A marginal rank-based inverse normal transformation approach to comparing multiple clinical trial endpoints. AB - The increase in incidence of obesity and chronic diseases and their health care costs have raised the importance of quality diet on the health policy agendas. The healthy eating index is an important measure for diet quality which consists of 12 components derived from ratios of dependent variables with distributions hard to specify, measurement errors and excessive zero observations difficult to model parametrically. Hypothesis testing involving data of such nature poses challenges because the widely used multiple comparison procedures such as Hotelling's T(2) test and Bonferroni correction may suffer from substantial loss of efficiency. We propose a marginal rank-based inverse normal transformation approach to normalizing the marginal distribution of the data before employing a multivariate test procedure. Extensive simulation was conducted to demonstrate the ability of the proposed approach to adequately control the type I error rate as well as increase the power of the test, with data particularly from non symmetric or heavy-tailed distributions. The methods are exemplified with data from a dietary intervention study for type I diabetic children. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26990441 TI - Inhibition of Acute Lung Injury by TNFR-Fc through Regulation of an Inflammation Oxidative Stress Pathway. AB - BACKGROUND: Acute lung injury (ALI), characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema, and associated with a proteinaceous alveolar exudate, is a leading cause of morbidity and mortality. Currently, inflammation-oxidative stress interaction between TNF-alpha and NF-kappaB was identified as a key pathway of ALI. We hypothesized that a TNFR Fc fusion protein would have beneficial effects in experimental ALI, and sought to test this idea in mice by blocking TNF-alpha. METHODS AND RESULTS: Intratracheal instillation of lipopolysaccharide (LPS) into the lungs of ALI mice led to histiocyte apoptosis, and detection of serum and bronchoalveolar lavage fluid (BALF) cytokines, feedback between NF-kappaB and TNF-alpha, lung albumin leakage, lung damage, IkappaB kinase (IKK) and NF-kappaB activation, I-kappaB degradation, and oxidative injury. LPS administration raised pulmonary inflammation as reflected by increased inflammatory cytokines, alveoli protein concentration, and ALI scores. IKK is phosphorylated following LPS challenge, leading to I-kappaB degradation and NF-kappaB p65 phosphorylation. Furthermore, NF-kappaB is translocated into the nucleus and up-regulates TNF-alpha gene transcription. Infusion of TNFR-Fc 24h before LPS challenge significantly abrogated the increase of inflammatory cytokines, especially serum TNF-alpha concentration, as well as pulmonary alveoli protein levels, and diminished IKK and NF-kappaB activation and I-kappaB degradation. The nuclear translocation of NF-kappaB was inhibited, following by down-regulation of TNF-alpha gene transcription. In addition, LPS intratracheal instillation induced marked oxidative damage, such as a decrease in total anti-oxidation products and an increase in malondialdehyde (MDA), as well as up-regulation of oxidation enzymes. Histologic analysis and apoptosis scores revealed that the extent of tissue lesions was significantly reduced, but not abrogated, by TNF-alpha blockade. CONCLUSION: Treatment with LPS alone increased inflammation and oxidative stress in ALI mice, while administration of TNFR-Fc 24h before LPS challenge broke the feedback between NF-kappaB and TNF-alpha, resulting in decreased pulmonary inflammation/oxidative damage and tissue destruction. These results suggest a potential role for TNF-alpha therapy to treat clinical ALI. PMID- 26990443 TI - The differences in left atrial function between ischemic and idiopathic dilated cardiomyopathy patients: A two-dimensional speckle tracking imaging study. AB - PURPOSE: To evaluate left atrial (LA) function in patients with ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy via two-dimensional speckle-tracking imaging. METHODS: We measured the LA maximum volume, minimum volume, and volume before the atrial systole, and calculated total emptying volume, expansion index, active emptying volume, and fraction. We measured strain and strain rate during systole and late diastole using two-dimensional speckle-tracking imaging, and analyzed correlations between variables. RESULTS: We found no significant differences in LA size, left ventricle (LV) end-diastole diameter, LV ejection fraction (EF), E/A, E/e', deceleration time of the E wave, and effective mitral regurgitant orifice area between the DCM and the ICM group. However, the LA expansion index, active EF, systolic and late diastolic strain, and strain rate were lower in the ICM group (p < 0.05). The expansion index and active EF were positively correlated with the systolic strain rate and the absolute value of the late diastolic strain rate, respectively. CONCLUSIONS: LA basic echocardiographic variables did not reflect the differences between ICM and DCM patients, but the systolic and late diastolic strain, as well as the strain rate, were lower in DCM patients. Two-dimensional speckle-tracking imaging is a promising method to differentiate these patients. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:437-445, 2016. PMID- 26990444 TI - Importance of Pharmacological Evaluation in the Treatment of Poststroke Pain by Spinal Cord Stimulation. AB - OBJECTIVES: Spinal cord stimulation (SCS) is not typically recommended for the treatment of central poststroke pain (CPSP). We examined whether the pharmacological evaluation of CPSP is useful for selecting the candidates for SCS. MATERIALS AND METHODS: Changes in visual analog scale (VAS) scores for pain following pharmacological evaluation using morphine, thiopental, and ketamine were compared with those following SCS in 22 CPSP patients. RESULTS: Twelve of the 22 (54.5%) patients in the ketamine test and thiopental test, and 5 (22.7%) of the 22 patients in the morphine test showed a more than 40% reduction in VAS score and were judged as "sensitive." Pain relief by SCS was estimated as excellent (?60% VAS score reduction) in three patients, good (30-59% reduction) in nine patients, and fair (10-29% reduction) in seven patients 24 months after the start of SCS. The remaining 3 patients evaluated as having poor pain relief (<10% reduction) only underwent test SCS. VAS score reduction induced by SCS was more significant in ketamine-sensitive patients than in ketamine-resistant patients during the test SCS (p < 0.01, Mann-Whitney's U test) and 24 months after the start of chronic SCS (p < 0.05). However, there were no significant differences in results for thiopental-sensitive/thiopental-resistant or morphine sensitive/morphine-resistant patients during the test SCS and 24 months after chronic SCS. Analysis of the rate of VAS score reduction by pharmacological evaluation and SCS showed significant correlations with the results of the ketamine test (r = 0.670, p = 0.001, Pearson's correlation coefficient test), but not with those of the thiopental (r = 0.291, p = 0.231) or morphine test (r = 0.327, p = 0.175). CONCLUSION: We speculate that the pharmacological evaluation of CPSP patients can be a useful tool for selecting candidates for SCS. PMID- 26990445 TI - Regioconvergent and Enantioselective Rhodium-Catalyzed Hydroamination of Internal and Terminal Alkynes: A Highly Flexible Access to Chiral Pyrazoles. AB - The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with internal and terminal alkynes features an utmost chemo-, regio-, and enantioselective access to enantiopure allylic pyrazoles, readily available for incorporation in small-molecule pharmaceuticals. This methodology is distinguished by a broad substrate scope, resulting in a remarkable compatability with a variety of different functional groups. It furthermore exhibits an intriguing case of regio-, position-, and enantioselectivity in just one step, underscoring the sole synthesis of just one out of up to six possible products in a highly flexible approach to allylated pyrazoles by emanating from various internal and terminal alkynes. PMID- 26990446 TI - Dual Palladium(II)/Tertiary Amine Catalysis for Asymmetric Regioselective Rearrangements of Allylic Carbamates. AB - The streamlined catalytic access to enantiopure allylic amines as valuable precursors towards chiral beta- and gamma-aminoalcohols as well as alpha- and beta-aminoacids is desirable for industrial purposes. In this article an enantioselective method is described that transforms achiral allylic alcohols and N-tosylisocyanate in a single step into highly enantioenriched N-tosyl protected allylic amines via an allylic carbamate intermediate. The latter is likely to undergo a cyclisation-induced [3,3]-rearrangement catalysed by a planar chiral pentaphenylferrocene palladacycle in cooperation with a tertiary amine base. The otherwise often indispensable activation of palladacycle catalysts by a silver salt is not required in the present case and there is also no need for an inert gas atmosphere. To further improve the synthetic value, the rearrangement was used to form dimethylaminosulfonyl-protected allylic amines, which can be deprotected under non-reductive conditions. PMID- 26990448 TI - Wheat ear carbon assimilation and nitrogen remobilization contribute significantly to grain yield. AB - The role of wheat ears as a source of nitrogen (N) and carbon (C) in the grain filling process has barely been studied. To resolve this question, five wheat genotypes were labeled with 15 N-enriched nutrient solution. N remobilization and absorption were estimated via the nitrogen isotope composition of total organic matter and Rubisco. Gas exchange analyses showed that ear photosynthesis contributed substantially to grain filling in spite of the great loss of C due to respiration. Of the total kernel N, 64.7% was derived from the N acquired between sowing and anthesis, while the remaining 35.3% was derived from the N acquired between anthesis and maturity. In addition, 1.87 times more N was remobilized to the developing kernel from the ear than from the flag leaf. The higher yielding genotypes showed an increased N remobilization to the kernel compared to the lower yielding genotypes. In addition, the higher yielding genotypes remobilized more N from the ears to the kernel than the lower yielding genotypes, while the lower yielding genotypes remobilized more N from the flag leaf to the kernel. Therefore, the ears contribute significantly toward fulfilling C and N demands during grain filling. PMID- 26990449 TI - Comparison of maturational process of hearing threshold in early life between at risk and low-risk preterm infants. AB - AIM: To detect any abnormality in the maturational process of hearing threshold during the early life in at-risk preterm infants. STUDY DESIGN: The threshold of brainstem auditory evoked response was recorded and analyzed longitudinally from 30 to 42weeks of postconceptional age in 357 at-risk infants born at 23-36weeks of gestation. The results were compared with those in 82 low-risk infants born at 30-42weeks at various postconceptional ages. RESULTS: From 31 to 42weeks, the response threshold in the at-risk infants was consistently slightly higher than that in the low-risk infants. No statistically significant difference was found between the two groups of infants at any designated postconceptional ages. The threshold in the at-risk infants born at 23-29weeks of gestation tended to be higher than those born at 30-36weeks at various postconceptional ages, but the difference did not reach statistical significance. There was also no significant difference in the slope of BAER threshold-age function between the at-risk infants, irrespective of gestational ages, and the low-risk infants. CONCLUSION: During the early life, hearing threshold in at-risk preterm, mainly very preterm, infants is marginally elevated, but the maturational process of the threshold is generally similar to that in low-risk infants, without notable abnormality. PMID- 26990447 TI - PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration. AB - The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP "core components" (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia. PMID- 26990450 TI - Molecular dynamics and composition of crude oil by low-field nuclear magnetic resonance. AB - Nuclear magnetic resonance (NMR) techniques are widely used to identify pure substances and probe protein dynamics. Oil is a complex mixture composed of hydrocarbons, which have a wide range of molecular size distribution. Previous work show that empirical correlations of relaxation times and diffusion coefficients were found for simple alkane mixtures, and also the shape of the relaxation and diffusion distribution functions are related to the composition of the fluids. The 2D NMR is a promising qualitative evaluation method for oil composition. But uncertainty in the interpretation of crude oil indicated further study was required. In this research, the effect of each composition on relaxation distribution functions is analyzed in detail. We also suggest a new method for prediction of the rotational correlation time distribution of crude oil molecules using low field NMR (LF-NMR) relaxation time distributions. A set of down-hole NMR fluid analysis system is independently designed and developed for fluid measurement. We illustrate this with relaxation-relaxation correlation experiments and rotational correlation time distributions on a series of hydrocarbon mixtures that employ our laboratory-designed downhole NMR fluid analyzer. The LF-NMR is a useful tool for detecting oil composition and monitoring oil property changes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990451 TI - The effect of dietary approaches to stop hypertension (DASH) diet on weight and body composition in adults: a systematic review and meta-analysis of randomized controlled clinical trials. AB - BACKGROUND: Dietary approaches to stop hypertension (DASH) diet is rich in foods that are proposed to be inversely associated with obesity. Therefore, DASH might better affect body weight; however, published data are conflicting. OBJECTIVE: To assess the effect of DASH on body weight and composition in adults. METHODS: PubMed, EMBASE, Scopus and Google scholar were searched up to December 2015, for relevant randomized controlled clinical trials. Mean changes in body weight, body mass index (BMI) and waist circumference (WC) were extracted. RESULTS: Thirteen articles (ten for body weight, six for BMI and two for WC) were eligible. Meta analysis revealed that adults on DASH diet lose more weight (weighted mean difference [WMD] = -1.42 kg, 95% confidence interval [95%CI]: -2.03, -0.82) in 8 24 weeks, BMI (WMD = -0.42 kg m(-2) , 95%CI: -0.64, -0.20) in 8-52 weeks and WC (WMD = -1.05 cm, 95%CI: -1.61, -0.49) in 24 weeks compared with controls. Low caloric DASH led to even more weight reduction when compared with other low energy diets. In addition, the effect was greater in overweight/obese participants and when compared with typical (Western or population's usual) diets. CONCLUSION: DASH diet is a good choice for weight management particularly for weight reduction in overweight and obese participants. PMID- 26990452 TI - Presence of Cerebral Microbleeds Is Unrelated to the Body Mass Index in Amerindians. A Population Study in Rural Ecuador (The Atahualpa Project). AB - BACKGROUND: Information on the relationship between the presence of cerebral microbleeds (CMB) and the body weight is inconsistent. Moreover, studies have been limited to Asian and White populations. We aimed at assessing the association between CMB and the body mass index (BMI) in an indigenous South American population. METHODS: CMB were identified by gradient-echo MRI and the BMI was calculated in community dwellers aged >=60 enrolled in the Atahualpa Project. The association between CMB and the BMI was examined in logistic regression models adjusted for relevant confounders. RESULTS: CMB were recognized in 41 (13%) out of 311 participants. These individuals were older, more often hypertensive, had a worse diet, had more severe white matter hyperintensities and strokes than those without CMB. Anthropometric measurements were 148 +/- 9 cm for height, 58 +/- 12 kg for weight, and 26.7 +/- 5 kg/m2 for the BMI. Multivariate models showed no association between the presence of CMB and the BMI (OR 0.97; 95% CI 0.89-1.05; p = 0.508). Analyses with CMB categorized according to their location did not show associations between strictly lobar or deep CMB and the BMI. CONCLUSION: The presence of CMB is unrelated to abnormal BMI determinations in Ecuadorian natives/mestizos. PMID- 26990453 TI - Utility of an allograft tendon for scoliosis correction via the costo-transverse foreman. AB - Current convex tethering techniques for treatment of scoliosis have centered on anterior convex staples or polypropylene tethers. We hypothesized that an allograft tendon tether inserted via the costo-transverse foramen would correct an established spinal deformity. In the pilot study, six 8-week-old pigs underwent allograft tendon tethering via the costo-transverse foreman or sham to test the strength of the transplanted tendon to retard spine growth. After 4 months, spinal deformity in three planes was induced in all animals with allograft tendons. In the treatment study, the allograft tendon tether was used to treat established scoliosis in 11 8-week-old pigs (spinal deformity > 50 degrees ). Once the deformity was observed (4 months) animals were assigned to either no treatment group or allograft tendon tether group and progression assessed by monthly radiographs. At final follow-up, coronal Cobb angle and maximum vertebral axial rotation of the treatment group was significantly smaller than the non-treatment group, whereas sagittal kyphosis of the treatment group was significantly larger than the non-treatment group. In sum, a significant correction was achieved using a unilateral allograft tendon spinal tether, suggesting that an allograft tendon tethering approach may represent a novel fusion-less procedure to correct idiopathic scoliosis. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:183-192, 2017. PMID- 26990454 TI - Managing the protein folding demands in the endoplasmic reticulum of plants. AB - Endoplasmic reticulum (ER) stress occurs in plants during certain developmental stages or under adverse environmental conditions, as a result of the accumulation of unfolded or misfolded proteins in the ER. To minimize the accumulation of misfolded proteins in the ER, a protein quality control (PQC) system monitors protein folding and eliminates misfolded proteins through either ER-associated protein degradation (ERAD) or autophagy. ER stress elicits the unfolded protein response (UPR), which enhances the operation in plant cells of the ER protein folding machinery and the PQC system. The UPR also reduces protein folding demands in the ER by degrading mRNAs encoding secretory proteins. In plants subjected to severe or chronic stress, UPR promotes programmed cell death (PCD). Progress in the field in recent years has provided insights into the regulatory networks and signaling mechanisms of the ER stress responses in plants. In addition, novel physiological functions of the ER stress responses in plants for coordinating plant growth and development with changing environment have been recently revealed. PMID- 26990455 TI - Calcineurin Inhibitor Minimization, Conversion, Withdrawal, and Avoidance Strategies in Renal Transplantation: A Systematic Review and Meta-Analysis. AB - Despite their clinical efficacy, concerns about calcineurin inhibitor (CNI) toxicity make alternative regimens that reduce CNI exposure attractive for renal transplant recipients. In this systematic review and meta-analysis, we assessed four CNI immunosuppression strategies (minimization, conversion, withdrawal, and avoidance) designed to reduce CNI exposure and assessed the impact of each on patient and allograft survival, acute rejection and renal function. We evaluated 92 comparisons from 88 randomized controlled trials and found moderate- to high strength evidence suggesting that minimization strategies result in better clinical outcomes compared with standard-dose regimens; moderate-strength evidence indicating that conversion to a mammalian target of rapamycin inhibitor or belatacept was associated with improved renal function but increased rejection risk; and moderate- to high-strength evidence suggesting planned CNI withdrawal could result in improved renal function despite an association with increased rejection risk. The evidence base for avoidance studies was insufficient to draw meaningful conclusions. The applicability of the review is limited by the large number of studies examining cyclosporine-based strategies and low-risk populations. Additional research is needed with tacrolimus-based regimens and higher risk populations. Moreover, research is necessary to clarify the effect of induction and adjunctive agents in alternative immunosuppression strategies and should include more comprehensive and consistent reporting of patient-centered outcomes. PMID- 26990456 TI - Characterizing the molecular features of ERG-positive tumors in primary and castration resistant prostate cancer. AB - BACKGROUND: The TMPRSS2-ERG gene fusion is detected in approximately half of primary prostate cancers (PCa) yet the prognostic significance remains unclear. We hypothesized that ERG promotes the expression of common genes in primary PCa and metastatic castration-resistant PCa (CRPC), with the objective of identifying ERG-associated pathways, which may promote the transition from primary PCa to CRPC. METHODS: We constructed tissue microarrays (TMA) from 127 radical prostatectomy specimens, 20 LuCaP patient-derived xenografts (PDX), and 152 CRPC metastases obtained immediately at time of death. Nuclear ERG was assessed by immunohistochemistry (IHC). To characterize the molecular features of ERG expressing PCa, a subset of IHC confirmed ERG+ or ERG- specimens including 11 radical prostatectomies, 20 LuCaP PDXs, and 45 CRPC metastases underwent gene expression analysis. Genes were ranked based on expression in primary PCa and CRPC. Common genes of interest were targeted for IHC analysis and expression compared with biochemical recurrence (BCR) status. RESULTS: IHC revealed that 43% of primary PCa, 35% of the LuCaP PDXs, and 18% of the CRPC metastases were ERG+ (12 of 48 patients [25%] had at least one ERG+ metastasis). Based on gene expression data and previous literature, two proteins involved in calcium signaling (NCALD, CACNA1D), a protein involved in inflammation (HLA-DMB), CD3 positive immune cells, and a novel ERG-associated protein, DCLK1 were evaluated in primary PCa and CRPC metastases. In ERG+ primary PCa, a weak association was seen with NCALD and CACNA1D protein expression. HLA-DMB association with ERG was decreased and CD3 cell number association with ERG was changed from positive to negative in CRPC metastases compared to primary PCa. DCLK1 was upregulated at the protein level in unpaired ERG+ primary PCa and CRPC metastases (P = 0.0013 and P < 0.0001, respectively). In primary PCa, ERG status or expression of targeted proteins was not associated with BCR-free survival. However, for primary PCa, ERG+DCLK1+ patients exhibited shorter time to BCR (P = 0.06) compared with ERG+DCLK1- patients. CONCLUSIONS: This study examined ERG expression in primary PCa and CRPC. We have identified altered levels of inflammatory mediators associated with ERG expression. We determined expression of DCLK1 correlates with ERG expression and may play a role in primary PCa progression to metastatic CPRC. Prostate 76:810-822, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990458 TI - Thiopurines best practice. PMID- 26990457 TI - Hyperpolarized (13)C-lactate to (13)C-bicarbonate ratio as a biomarker for monitoring the acute response of anti-vascular endothelial growth factor (anti VEGF) treatment. AB - Hyperpolarized [1-(13)C]pyruvate MRS provides a unique imaging opportunity to study the reaction kinetics and enzyme activities of in vivo metabolism because of its favorable imaging characteristics and critical position in the cellular metabolic pathway, where it can either be reduced to lactate (reflecting glycolysis) or converted to acetyl-coenzyme A and bicarbonate (reflecting oxidative phosphorylation). Cancer tissue metabolism is altered in such a way as to result in a relative preponderance of glycolysis relative to oxidative phosphorylation (i.e. Warburg effect). Although there is a strong theoretical basis for presuming that readjustment of the metabolic balance towards normal could alter tumor growth, a robust noninvasive in vivo tool with which to measure the balance between these two metabolic processes has yet to be developed. Until recently, hyperpolarized (13)C-pyruvate imaging studies had focused solely on [1 (13)C]lactate production because of its strong signal. However, without a concomitant measure of pyruvate entry into the mitochondria, the lactate signal provides no information on the balance between the glycolytic and oxidative metabolic pathways. Consistent measurement of (13)C-bicarbonate in cancer tissue, which does provide such information, has proven difficult, however. In this study, we report the reliable measurement of (13)C-bicarbonate production in both the healthy brain and a highly glycolytic experimental glioblastoma model using an optimized (13)C MRS imaging protocol. With the capacity to obtain signal in all tumors, we also confirm for the first time that the ratio of (13)C-lactate to (13)C-bicarbonate provides a more robust metric relative to (13)C-lactate for the assessment of the metabolic effects of anti-angiogenic therapy. Our data suggest a potential application of this ratio as an early biomarker to assess therapeutic effectiveness. Furthermore, although further study is needed, the results suggest that anti-angiogenic treatment results in a rapid normalization in the relative tissue utilization of glycolytic and oxidative phosphorylation by tumor tissue. PMID- 26990459 TI - Estimating indices of range shifts in birds using dynamic models when detection is imperfect. AB - There is intense interest in basic and applied ecology about the effect of global change on current and future species distributions. Projections based on widely used static modeling methods implicitly assume that species are in equilibrium with the environment and that detection during surveys is perfect. We used multiseason correlated detection occupancy models, which avoid these assumptions, to relate climate data to distributional shifts of Louisiana Waterthrush in the North American Breeding Bird Survey (BBS) data. We summarized these shifts with indices of range size and position and compared them to the same indices obtained using more basic modeling approaches. Detection rates during point counts in BBS surveys were low, and models that ignored imperfect detection severely underestimated the proportion of area occupied and slightly overestimated mean latitude. Static models indicated Louisiana Waterthrush distribution was most closely associated with moderate temperatures, while dynamic occupancy models indicated that initial occupancy was associated with diurnal temperature ranges and colonization of sites was associated with moderate precipitation. Overall, the proportion of area occupied and mean latitude changed little during the 1997 2013 study period. Near-term forecasts of species distribution generated by dynamic models were more similar to subsequently observed distributions than forecasts from static models. Occupancy models incorporating a finite mixture model on detection - a new extension to correlated detection occupancy models - were better supported and may reduce bias associated with detection heterogeneity. We argue that replacing phenomenological static models with more mechanistic dynamic models can improve projections of future species distributions. In turn, better projections can improve biodiversity forecasts, management decisions, and understanding of global change biology. PMID- 26990460 TI - Optical Dental Whitening Efficacy of Blue Covarine Toothpaste in Teeth Stained by Different Colors. AB - OBJECTIVE: Evaluate the immediate and cumulative optical whitening efficacy of a blue covarine toothpaste. MATERIALS AND METHODS: 180 bovine tooth specimens with similar shade (DeltaE < 3.5) were staining of different beverage: black tea(BT), green tea (GT), red wine (RW), orange soda (OS), and brazilian acai juice (AJ), and then submitted to tooth brushing with a blue covarine toothpaste (Op) or a control abrasive toothpaste (Ab). The whitening effect was evaluated at baseline (B), after staining (S), after 1 day (1D) and 7 days of cumulative use of toothpastes (7D). The color shade chances were assessment by Vita Easyshade reflectance spectroscope and the data of CIELab color coordinates (L*, a*, and b*), color difference (DeltaE) and the whiteness index optimized (WIO), were analyzed by two-way mixed analysis of variance (ANOVA) for repeated measures and Bonferroni-corrected t-tests (alpha = 0.05). RESULTS: The analysis showed statistically significant differences before and after staining by colored beverages (p < 0.05), but no differences were found due to the action of toothpaste (p > 0.05), in the CIELab coordinates, DeltaE and WIO index. CONCLUSIONS: The use of toothpastes (Op or Ab) reduced the dental staining caused by different colored beverage, but the whitening effect of blue covarine toothpaste could not be confirmed (p > 0.05). PMID- 26990461 TI - A sexually dimorphic effect of cholera toxin: rapid changes in colonic motility mediated via a 5-HT3 receptor-dependent pathway in female C57Bl/6 mice. AB - KEY POINTS: Cholera causes more than 100,000 deaths each year as a result of severe diarrhoea, vomiting and dehydration due to the actions of cholera toxin; more females than males are affected. Cholera toxin induces hypersecretion via release of mucosal serotonin and over-activation of enteric neurons, but its effects on gastrointestinal motility are not well characterized. We found that cholera toxin rapidly and reversibly reduces colonic motility in female mice in oestrus, but not in males or females in prooestrus, an effect mediated by 5-HT in the colonic mucosa and by 5-HT3 receptors. We show that the number of mucosal enterochromaffin cells containing 5-HT changes with the oestrous cycle in mice. These findings indicate that cholera toxin's effects on motility are rapid and depend on the oestrous cycle and therefore can help us better understand differences in responses in males and female patients. ABSTRACT: Extensive studies of the mechanisms responsible for the hypersecretion produced by cholera toxin (CT) have shown that this toxin produces a massive over-activation of enteric neural secretomotor circuits. The effects of CT on gastrointestinal motility, however, have not been adequately characterized. We investigated effects of luminal CT on neurally mediated motor activity in ex vivo male and female mouse full length colon preparations. We used video recording and spatiotemporal maps of contractile activity to quantify colonic migrating motor complexes (CMMCs) and resting colonic diameter. We compared effects of CT in female colon from wild-type and mice lacking tryptophan hydroxylase (TPH1KO). We also compared CMMCs in colons of female mice in oestrus with those in prooestrus. In female (but not male) colon, CT rapidly, reversibly and concentration dependently inhibits CMMC frequency and induces a tonic constriction. These effects were blocked by granisetron (5-HT3 antagonist) and were absent from TPH1KO females. CT effects were prominent at oestrus but absent at prooestrus. The number of EC cells containing immunohistochemically demonstrable serotonin (5 HT) was 30% greater in female mice during oestrus than during prooestrus or in males. We conclude that CT inhibits CMMCs via release of mucosal 5-HT, which activates an inhibitory pathway involving 5-HT3 receptors. This effect is sex- and oestrous cycle-dependent and is probably due to an oestrous cycle-dependent change in the number of 5-HT-containing EC cells in the colonic mucosa. PMID- 26990463 TI - Engaging patients and families in communication across transitions of care: an integrative review protocol. AB - AIM: To describe an integrative review protocol to analyse and synthesize peer reviewed research evidence in relation to engagement of patients and their families in communication during transitions of care to, in and from acute care settings. BACKGROUND: Communication at transitions of care in acute care settings can be complex and challenging, with important information about patients not always clearly transferred between responsible healthcare providers. Involving patients and their families in communication during transitions of care may improve the transfer of clinical information and patient outcomes and prevent adverse events during hospitalization and following discharge. Recently, optimizing patient and family participation during care transitions has been acknowledged as central to the implementation of patient-centred care. DESIGN: Integrative review with potential for meta-analysis and application of framework synthesis. REVIEW METHOD: The review will evaluate and synthesize qualitative and quantitative research evidence identified through a systematic search. Primary studies will be selected according to inclusion criteria. Data collection, quality appraisal and analysis of the evidence will be conducted by at least two authors. Nine electronic databases (including CINAHL and Medline) will be searched. The search will be restricted to 10 years up to December 2013. Data analysis will include content and thematic analysis. DISCUSSION: The review will seek to identify all types of patient engagement activities employed during transitions of care communication. The review will identify enablers for and barriers to engagement for patients, families and health professionals. Key strategies and tools for improving patient engagement, clinical communication and promoting patient-centred care will be recommended based on findings. PMID- 26990462 TI - A Dual-Targeting Octaguanidine-Doxorubicin Conjugate Transporter for Inducing Caspase-Mediated Apoptosis on Folate-Expressing Cancer Cells. AB - An efficient synthetic framework was assembled (G8-FKE-FA-Dox), consisting of a lysosome-targeting octaguanidine molecular transporter with a cathepsin B (cath B)-specific peptide substrate, folic acid, and the potent chemotherapeutic drug doxorubicin (Dox). Because the folate receptor (FR) and cath B are overexpressed in malignant cells, this transporter conjugate successfully executed lysosome mediated transport of Dox to FR-positive tumor cells, illustrating this framework as an excellent targeted drug delivery system (TDDS). G8-FKE-FA-Dox was shown to exhibit selective toxicity toward FR-overexpressing cancer cells, with an IC50 value superior to that of the USFDA-approved Lipodox(TM) and proportional to that of free Dox via selective induction of apoptosis by the activation of caspases 8, 9, and 3. This TDDS was observed to be nontoxic to red blood cells and lymphocytes at neutral pH. Furthermore the tumor-targeting dissemination pattern of this system was revealed by monitoring the in vivo biodistribution of the carrier (G8-FKE-FA-FL) in normal and FR-overexpressing tumor-bearing mice. PMID- 26990464 TI - Body composition analysis for discrimination of prolonged hospital stay in colorectal cancer surgery patients. AB - We aimed to ascertain the implementation of body composition assessment, by means of fat-free mass index (FFMI), fat mass index (FMI) and presence of sarcopenic obesity, in colorectal cancer population, on the basis of hospital length of stay (LOS) determination and to benchmark their discriminatory performance with other nutrition status algorithms, such as body mass index (BMI) and Malnutrition Universal Screening Tool (MUST). Ninety adult patients with operable colorectal cancer were enrolled. Study parameters included demographic and anthropometric data registration, BMI and MUST calculation and body composition parameters measurement within 24-h post-admission. Hospital LOS constituted the outcome of interest, using 7 days as cut-off point. Fifty-one patients (56.7%) were hospitalised for <=7 days. The presence of sarcopenic obesity affected adversely hospital LOS (OR, 9.236; 95% CI, 3.278-26.173, P = 0.000). Low FFMI (OR, 7.457; 95% CI, 2.868-19.390, P = 0.000), malnutrition according to MUST (OR, 2.632; 95% CI, 1.280-5.413, P = 0.009) and high FMI (2.133; 95% CI, 1.111-4.094, P = 0.023) were the most powerful discriminators of accelerated hospitalisation. Loss of lean body tissue, gain of adipose tissue and sarcopenic obesity confer noteworthy prognostic value being superior or equivalent to MUST in terms of hospital LOS determination in colorectal cancer resection setting. BMI presents inferior discrimination performance in this field. PMID- 26990465 TI - Language processing in bilingual aphasia: a new insight into the problem. AB - There is increasing evidence that a bilingual person should not be considered as two monolinguals in a single body, a view that has gradually been adopted in the diagnosis and treatment of bilingual aphasia. However, its investigation is complicated due to the large variety in possible language combinations, pre- and postmorbid language proficiencies, and age of second language acquisition. Furthermore, the tests and tasks used to assess linguistic capabilities differ in almost every study, hindering a direct comparison of their outcomes. Behavioral, electrophysiological, and neuroimaging data from healthy population show that the processing of second language domains (semantics, syntax, morphology) depends on factors such as age and method of acquisition, proficiency level and environment in which the second language was acquired. A number of single and multiple case reports that rely on behavioral testing of bilingual aphasics replicate these results. Additionally, they show that the patient's performance depends on the size and location of the lesion, as well as language typology and morphological characteristics. Furthermore, the impairment and recovery patterns and recovery generalization from treated to untreated language depend on the lexical and orthographic distances between the two languages. For healthy bilinguals, language processing is usually studied in comparison to monolinguals. We advocate that a good starting point for identifying patterns specific for bilingual aphasia is to compare patient studies of bilinguals and monolinguals. PMID- 26990466 TI - A 10-year review of outpatient skin biopsy results and skin cancer subtypes. AB - The results of skin biopsies over a 10 year period were reviewed from the outpatient dermatology clinic at the Brody School of Medicine in Greenville, North Carolina. This research was conducted because there are very few studies that characterize this information over a long-term horizon. The biopsy rate per patient encounter, the clinical reason for the biopsy, the biopsy outcomes, the distribution of cutaneous malignancies per encounter, and the distribution of the subtypes of basal cell carcinoma, squamous cell carcinoma, and melanoma were analyzed. Biopsy logs from January 1, 2001 to December 31, 2010 were reviewed. Our investigation found that 20% of patient encounters resulted in a biopsy. Of these biopsies, 87.9% were performed to rule out malignancy and 12.1% were completed on patients suspected of having inflammatory skin conditions. The basal cell carcinomas diagnosed in Greenville, NC have more aggressive histologic subtypes compared to other studies, whereas the squamous cell carcinomas and melanomas were less aggressive. PMID- 26990467 TI - Prevalence of osteoma cutis in the maxillofacial region and classification of its radiographic pattern in cone beam CT. AB - BACKGROUND: Osteoma cutis is a rare soft tissue ossification of cutaneous tissue and may be primary or secondary. In the majorityof cases it is clinically asymptomatic and may detected incidentally on radiographic examination. Cone beam computed tomography (CBCT) has can be of great assistance in the detection of this asymptomatic lesion. OBJECTIVES: In this retrospective study, the prevalence and different radiographic appearance of osteoma cutis was evaluated. MATERIALS AND METHODS: A total of 6,500 CBCT images were evaluated for the presence of osteoma cutis. Ectopic existence of calcified tissue within the soft tissue of the dermis or epidermis that was incompatible with the calcification of other anatomic structures or soft tissue calcifications was considered to be osteoma cutis. Accordingly, the detected patterns were divided into four distinct groups: (1) a single nodule, (2) plate-like lesion, (3) single or multiple depth lesion(s), trans-epidermal, and (4) multiple, disseminated lesions of various sizes known as multiple miliary. The data were evaluated in terms of prevalence and variations. The frequency, total prevalence, percentage and the prevalence of different radiographic forms of this lesion were calculated. RESULTS: One hundred and forty eight (2.27%) cases of 6,500 evaluated tomograms had osteoma cutis. Of these, 5 (0.07%) were in the form of a single nodule, 4 (0.06%) were single, plate-like lesions, 7 (0.1%) were multiple plate-like lesions, 2 (0.03%) were in the form of a deep thread-like lesion, and 130 (2%) presented as multiple disseminated lesions. CONCLUSION: According to the radiographic views, osteoma cutis may be categorized into single nodular, single or multiple plate- like, deep, and multiple disseminated forms. Of the mentioned radiogarphic patterns, the multiple disseminated form (miliary) hada higher prevalence in our study. CBCT images enable accurate evaluation of the nature and frequency of osteoma cutis. PMID- 26990468 TI - Poikiloderma-like cutaneous amyloidosis--a rare presentation of primary localized cutaneous amyloidosis. AB - Poikiloderma-like cutaneous amyloidosis (PCA) is a rare variant of primary cutaneous amyloidosis. It was first described in 1929 and there are two clinical forms of PCA, the ordinary type and PCA syndrome. The characteristics of PCA include poikiloderma-like skin changes, lichenoid papules, blister formation, and cutaneous amyloid deposits on histological examination. These skin lesions usually occur at the extremities, consistent with the few cases that have been reported. We present a case of a 62-year-old man who presented with the features of poikiloderma-like cutaneous amyloidosis. Diagnosis of this unique condition is a challenge and a skin biopsy is necessary in such instances. A discussion of the differential diagnosis of this condition is also included. PMID- 26990469 TI - Cyclosporine-induced sebaceous hyperplasia in a hematopoetic stem cell transplant patient: delayed onset of a common adverse event. AB - Cyclosporine-induced sebaceous hyperplasia (SH) is a well-documented entity, occurring in up to 30% of renal transplant patients treated with cyclosporine and has also been reported to occur following heart or hematopoetic stem cell transplantation (HCST). Cyclosporine has a stimulatory effect on undifferentiated sebocytes, resulting in the clinical and histologic findings in these patients. Sebaceous hyperplasia most commonly presents as asymptomatic papules over the face, chest, or groin. Herein we describe a case of a 27-year-old man who developed facial sebaceous hyperplasia five months after completing cyclosporine therapy for cutaneous graft versus host disease (GVHD) following HSCT. PMID- 26990470 TI - Cutaneous Rosai-Dorfman Disease in a Patient with Human Immunodeficiency Virus. AB - Rosai-Dorfman disease rarely presents in a solely cutaneous form. A subset of patients with skin limited disease have associated immune disorders such as lupus, autoimmune hemolytic anemia, and Crohn disease. We report an interesting case of cutaneous Rosai Dorfman disease in a patient with human immunodeficiency virus (HIV). PMID- 26990471 TI - Concomitant pemphigus vulgaris and pemphigoid gestationis: a case report and review of the literature. AB - Pemphigus and pemphigoid are two unique acquired immunobullous diseases with distinct clinical presentations, histological findings, and characteristic serology; they are rarely reported to coexist in the same patient. Herein we present a 29-year-old woman with a history of pemphigus vulgaris, diagnosed by histology and positive desmoglein-3 antibodies on ELISA. She presented to our clinic shortly after the delivery of her first child with tense vesicles and bullae on an erythematous base on her abdomen. Biopsy was consistent with pemphigoid gestationis and direct immunofluorescence confirmed the diagnosis. To our knowledge, there are no other reported cases of pemphigoid gestationis occurring in a patient with pemphigus vulgaris. PMID- 26990472 TI - Disseminated Candida tropicalis presenting with Ecthyma-Gangrenosum-like Lesions. AB - Disseminated candidiasis in immunosuppressed patients has been classically associated with an erythematous papular eruption, however more severe presentations are possible. We present a patient who developed disseminated Candida tropicalis that presented with hemorrhagic bullae that progressed to large necrotic ulcers. PMID- 26990473 TI - Isolated benign primary cutaneous plasmacytosis in an adult Indian male. AB - Primary cutaneous plasmacytosis (PCP) is an uncommon reactive lymphoplasmacytic disorder of uncertain etiology. It has been mainly described in patients of Japanese descent, with only few reports in Caucasians and Chinese. We present a case of isolated benign PCP in a 45-year-old man, who clinically manifested with a localized ulcerated nodule overlying a hyperpigmented plaque on the upper back. To the best of our knowledge, PCP from India has not been described before. PMID- 26990474 TI - Multifocal extramammary Paget's disease-associated adenocarcinoma: a rare condition of flexoral skin of multiple sites. AB - Extramammary Paget disease (EMPD) is a rare malignant neoplasm of apocrine sweat glands that is morphologically and histologically identical to Paget disease of the breast. The primary lesion is usually a solitary, well-demarcated, erythematous, scaly plaque that may contain crust, erosions, or ulcerations. The vulva is the most common site, but any area containing apocrine sweat glands may be involved. We present a case of triple extramammary Paget disease of the groin and bilateral axillae in a diabetic patient whose axillary lesions appeared consistent with acanthosis nigricans. This case demonstrates the need to consider EMPD in the evaluation of acanthosis of the axilla given its ability to mimic more common conditions. PMID- 26990475 TI - Scurvy in the present times: vitamin C allergy leading to strict fast food diet. AB - Scurvy results from a deficiency of vitamin C, a nutrient otherwise known as ascorbic acid. Today, scurvy is rare yet emerges in select patients. The patient reported herein developed scurvy secondary to deliberate avoidance of vitamin C rich foods. Classic cutaneous manifestations of scurvy include follicular hyperkeratosis and perifollicular hemorrhage encompassing coiled "corkscrew" hairs and hairs bent into "swan-neck" deformities. Ecchymoses, purpura, and petechiae are also characteristically prominent. Classic oral abnormalities include erythematous, swollen gingivae that hemorrhage from subtle microtrauma.Subungual linear splinter hemorrhages may also manifest as a sign of the disease. To establish the diagnosis requirements include characteristic physical exam findings, evidence of inadequate dietary intake, and rapid reversal of symptoms upon supplementation. Although unnecessary for diagnosis, histological findings demonstrate perifollicular inflammation and hemorrhage, fibrosis, and hyperkeratosis, amongst dilated hair follicles and keratin plugging. Although citrus fruit allergies have been historically documented, ascorbic acid has not been previously reported as an allergen. Although lacking absolute certainty, this report suggests a presumed case of ascorbic acid allergy based on patient history and favorable response to ascorbic acid desensitization therapy. PMID- 26990476 TI - Adenocarcinoma of the colon presenting with scrotal metastasis: case report and review of the literature. AB - BACKGROUND: The scrotum is an uncommon site for cutaneous metastases from visceral malignancies. PURPOSE: A man with colon cancer, which subsequently developed cutaneous metastasis to the scrotum is described. MATERIALS AND METHODS: PubMed medical database was used to search the following terms separately and in combination: cutaneous metastasis, skin metastasis, scrotal metastasis, scrotum, rectal cancer, and colon cancer. RESULTS: Cutaneous metastasis most frequently occur in the vicinity of the primary tumor. Skin sites of metastatic cancer may include the abdomen, back, chest, face, scalp, and genitalia. The reported patient developed metastatic cutaneous lesions of his colon cancer not only on the abdomen but also on the scrotum. Including our patient, 9 men have been described with metastatic colon or rectal carcinoma localized to the scrotum. The lesions were the presenting sign of malignancy in one man and in the others, the lesions appeared within 24 months of their initial diagnosis of cancer. The skin metastases were pleomorphic; they appeared as papules, nodules and/or cutaneous induration. Survival data was only reported in five of the patients. However, colon or rectal metastases to the scrotum is a poor prognostic sign with a mean survival time of 11 months. CONCLUSION: Scrotal metastases from carcinoma of the colon or rectum may be the initial presentation of malignancy or herald the discovery of recurrent disease. The morphology of the metastatic tumor is variable: papules, nodules and/or sclerosis. The development of scrotal metastases from colon or rectal carcinoma portends a poor prognosis. Most of the patients succumb to theirmetastatic disease within a year. PMID- 26990477 TI - Follicularly-based papules on the thigh of a young woman. AB - Varicella zoster virus (VZV) is an uncommon cause of folliculitis. We present a case of a 29-year-old woman who presented with an atypical follicularly-based eruption localized to her inner thigh with an associated pain in her lower back and inner thigh prior to the papular eruption. She was successfully treated with valacyclovir 1,000 mg three times daily with no complications. PMID- 26990478 TI - A unexpected growth arising within nevus sebaceous of Jadassohn. AB - The predisposition to epithelial neoplasms in nevus sebaceous is well established; most tumors occur in adults and are benign. Hidradenoma is a relatively rare benign tumor of sweat gland origin that can rarely arise within a nevus sebaceous. We present an interesting case of a hidradenoma and sebaceoma arising within a nevus sebaceous and present a literature review of the 2 conditions. Even though hidradenoma is a benign tumor, we would advocate complete excision given the potential for malignant transformation. PMID- 26990479 TI - Giant molluscum contagiosum presenting as lid neoplasm in an immunocompetent child. AB - A three-year-old boy presented to our oculoplastic clinic with complaints of painless gradually increasing right upper lid mass for the last 6 months. On examination a firm mass measuring roughly 1x1 cm was present on the upper lid. The mass was non tender with fine superficial vessels running over it. A differential diagnosis of epidermoid cyst, vascular malformation, pilomatrixoma, and juvenile xanthogranuloma was considered. The patient underwent excisional biopsy of the mass. On gross examination the mass had a brain like appearance. Histopathological examination confirmed the diagnosis of molluscum contagiosum. It is rare for molluscum contagiosum to present as a solitary lid tumor. A brain like appearance of the excised mass can provide a clue towards the diagnosis. PMID- 26990480 TI - Radiation-induced localized bullous pemphigoid in a patient with breast carcinoma. AB - Bullous pemphigoid (BP) is a common pemphigoid disorder, which is localized in approximately 16-29% of cases. A small subset of localized BP cases is associated with prior radiation therapy, most commonly for breast carcinoma. We present a patient with an unusual presentation of localized BP after receiving partial accelerated breast irradiation (a type of brachytherapy that has a decreased amount of radiation to the skin as compared to the more common external beam radiation therapy). PMID- 26990481 TI - Methotrexate-induced necrolysis in tumoral-stage mycosis fungoides: a challenging diagnosis. AB - Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous infusions of methotrexate. Since then, few cases of methotrexate induced skin ulcers in patients with mycosis fungoides have been published. We report an additional patient with erythrodermic mycosis fungoides who developed cutaneous ulcerations as a sole manifestation of methotrexate toxicity. PMID- 26990482 TI - C-Kit non-mutated metastatic melanoma showing positive response to Nilotinib. AB - Melanoma is an aggressive tumor with advanced disease characterized by widespread metastatic lesions and the tumor has traditionally been resistant to most forms of treatment. Indeed, metastatic melanoma has a very poor prognosis with a median survival time of 8-9 months and an estimated 3-year survival rate of less than 15%. Recent advances in our understanding of the genetic profile of melanoma cells and the molecular factors that drive malignant transformation have resulted in the identification of numerous new therapeutic targets. KIT is an established therapeutic target in cancers with activating mutations of KIT, such as gastrointestinal stromal tumors (GIST), and considerable efficacy has been achieved with various small molecule inhibitors of KIT including imatinib mesylate. Nilotinib is an inhibitor of ligand-induced PDGFRalpha and PDFGRbeta kinase activity and autophosphorylation of constitutively activated KIT harboring exon 13 or exon 11 mutations (IC50 values of 0.2 and 0.027 MUmol/L, respectively), with efficacy comparable to that of imatinib. We report a case of non-kit mutated metastatic vaginal melanoma showing impressive response to nilotinib. PMID- 26990483 TI - Inhibition of endoplasmic reticulum stress improves coronary artery function in type 2 diabetic mice. AB - NEW FINDINGS: What is the central question of this study? Endoplasmic reticulum (ER) stress has been reported to be involved in type 2 diabetes; however, the role of exacerbated ER stress in vascular dysfunction in type 2 diabetes remains unknown. What is the main finding and its importance? The main findings of this study are that ER stress is increased in the coronary arteries in type 2 diabetes, and inhibition of ER stress using taurine-conjugated ursodeoxycholic acid improves vascular function, which is associated with normalization of the myogenic response and endothelium-dependent relaxation. Vascular dysfunction is a major complication in type 2 diabetes. Although endoplasmic reticulum (ER) stress has been suggested to be a contributory factor in cardiovascular diseases, the relationship between ER stress and vascular dysfunction in type 2 diabetes remains unclear. Thus, in the present study, we examined whether ER stress contributes to coronary artery dysfunction and whether inhibition of ER stress ameliorates vascular function in type 2 diabetes. Type 2 diabetic mice and their control counterparts were treated with an ER stress inhibitor (taurine-conjugated ursodeoxycholic acid, 150 mg kg(-1) day(-1) , by i.p. injection) for 2 weeks or not treated. The myogenic response and endothelium-dependent relaxation were measured in pressurized coronary arteries. In type 2 diabetic mice, blood glucose and body weight were elevated compared with control mice. The myogenic response was potentiated and endothelium-dependent relaxation impaired in coronary arteries from the type 2 diabetic mice. Interestingly, treatment with the ER stress inhibitor normalized the myogenic responses and endothelium-dependent relaxation. These data were associated with an increase in ER stress marker expression or phosphorylation (IRE1-XBP-1 and PERK-eIF2alpha) in type 2 diabetic mice, which were reduced by treatment with the ER stress inhibitor. Inhibition of ER stress normalizes the myogenic response and improves vascular function in type 2 diabetes. Therefore, ER stress could be a potential target for cardiovascular diseases in diabetes mellitus. PMID- 26990484 TI - Nanoporous metals for biodegradable implants: Initial bone mesenchymal stem cell adhesion and degradation behavior. AB - Nanostructured Fe-Mn and Fe-Mn-Zn metal scaffolds were generated through a well controlled selective leaching process in order to fulfill the growing demand for adjustable degradation rates and improved cellular response of resorbable materials. Mouse bone marrow mesenchymal stem cells (D1 ORL UVA) were seeded onto eleven, carefully chosen nanoporous surfaces for 24 h in vitro. Using a combination of fluorescence microscopy, scanning electron microscopy (SEM), and an MTS assay, it was discovered that scaffolds with nanoscale roughened surfaces had increased cell attachment by up to 123% compared to polished smooth Fe-Mn surfaces. Significant cell spreading and construction of cell multilayers were also apparent after 24 h, suggesting better adhesion. Additionally, static electrochemical polarization experiments revealed an improvement of up to 26% in the actual rate of biodegradation for Fe-Mn surface-modified materials. However, any residual concentration of zinc after leaching was shown to slightly increase corrosion resistance. The results demonstrate that selectively leached, nanostructured Fe-Mn surfaces have the potential of being tailored to a diverse set of transient implant scenarios, while also effectively boosting overall biocompatibility, initial cell attachment, and degradation rate. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1747-1758, 2016. PMID- 26990485 TI - A Thermally-Regenerative Ammonia-Based Flow Battery for Electrical Energy Recovery from Waste Heat. AB - Large amounts of low-grade waste heat (temperatures <130 degrees C) are released during many industrial, geothermal, and solar-based processes. Using thermally regenerative ammonia solutions, low-grade thermal energy can be converted to electricity in battery systems. To improve reactor efficiency, a compact, ammonia based flow battery (AFB) was developed and tested at different solution concentrations, flow rates, cell pairs, and circuit connections. The AFB achieved a maximum power density of 45 W m(-2) (15 kW m(-3) ) and an energy density of 1260 Wh manolyte (-3) , with a thermal energy efficiency of 0.7 % (5 % relative to the Carnot efficiency). The power and energy densities of the AFB were greater than those previously reported for thermoelectrochemical and salinity-gradient technologies, and the voltage or current could be increased using stacked cells. These results demonstrated that an ammonia-based flow battery is a promising technology to convert low-grade thermal energy to electricity. PMID- 26990487 TI - Nursing competency standards in primary health care: an integrative review. AB - AIMS AND OBJECTIVES: This paper reports an integrative review of the literature on nursing competency standards for nurses working in primary health care and, in particular, general practice. BACKGROUND: Internationally, there is growing emphasis on building a strong primary health care nursing workforce to meet the challenges of rising chronic and complex disease. However, there has been limited emphasis on examining the nursing workforce in this setting. DESIGN: Integrative review. METHODS: A comprehensive search of relevant electronic databases using keywords (e.g. 'competencies', 'competen*' and 'primary health care', 'general practice' and 'nurs*') was combined with searching of the Internet using the Google scholar search engine. Experts were approached to identify relevant grey literature. Key websites were also searched and the reference lists of retrieved sources were followed up. The search focussed on English language literature published since 2000. RESULTS: Limited published literature reports on competency standards for nurses working in general practice and primary health care. Of the literature that is available, there are differences in the reporting of how the competency standards were developed. A number of common themes were identified across the included competency standards, including clinical practice, communication, professionalism and health promotion. Many competency standards also included teamwork, education, research/evaluation, information technology and the primary health care environment. CONCLUSION: Given the potential value of competency standards, further work is required to develop and test robust standards that can communicate the skills and knowledge required of nurses working in primary health care settings to policy makers, employers, other health professionals and consumers. RELEVANCE TO CLINICAL PRACTICE: Competency standards are important tools for communicating the role of nurses to consumers and other health professionals, as well as defining this role for employers, policy makers and educators. Understanding the content of competency standards internationally is an important step to understanding this growing workforce. PMID- 26990486 TI - Time for Cigarette Smoke Exposure Chambers? PMID- 26990488 TI - Curiosity and independent reading among residents. PMID- 26990489 TI - A novel HLA-A*02 allele, A*02:543 was identified by polymerase chain reaction sequence-based typing in a Chinese cord blood donor. AB - HLA-A*02:543 differ from HLA-A*02:12 by two nucleotide substitutions. PMID- 26990490 TI - Clinical implications of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in treatment-naive chronic hepatitis B. AB - AIM: To examine the relationship between serum Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) levels and liver histological findings for patients with treatment naive chronic hepatitis B (CHB). METHODS: A total of 189 treatment naive-CHB patients were analyzed. We examined the effect of pretreatment serum WFA+ -M2BP levels on histological findings compared with other laboratory markers, including aspartate aminotransferase (AST) to platelet ratio index, Fibrosis-4 index, platelet count, AST to alanine aminotransferase (ALT) ratio, and hyaluronic acid as liver fibrosis markers, and AST value, ALT value, and serum interferon-gamma-inducible protein-10 level as liver inflammation markers. RESULTS: The WFA+ -M2BP value ranged from 0.3 cut-off index (COI) to 12.9 COI (median value, 1.2 COI). The degree of liver fibrosis was significantly stratified according to WFA+ -M2BP level in each group except for groups F2 and F3 and the degree of liver inflammation activity was significantly stratified according to WFA+ -M2BP level in each group. For predicting F4, WFA+ M2BP level yielded the highest area under the receiver operating characteristic curve (AUROC) with a level of 0.87 and for predicting advanced liver fibrosis (>=F3) and significant liver fibrosis (>=F2), WFA+ -M2BP level yielded the second highest AUROCs (both, 0.77) among six fibrotic markers. For predicting severe (A3) or significant liver inflammation activity (>=A2), AUROCs of WFA+ -M2BP level were 0.78 and 0.76. CONCLUSION: The WFA+ -M2BP level can be a useful marker for assessing liver histological findings in patients with treatment-naive CHB, although it has several limitations. PMID- 26990491 TI - Thermochemistry and Kinetic Analysis of the Unimolecular Oxiranyl Radical Dissociation Reaction: A Theoretical Study. AB - Oxirane structures are important in organic synthesis, and they are important initial products in the oxidation reactions of alkyl radicals. The thermochemical properties (enthalpy of formation, entropy, and heat capacity) for the reaction steps of the unimolecular oxiranyl radical dissociation reaction are determined and compared with the available literature. The overall ring opening and subsequent steps involve four types of reactions: beta-scission ring opening, intramolecular hydrogen transfer, beta-scission hydrogen elimination, and beta scission methyl radical elimination. The enthalpies of formation of the transition states are determined and evaluated using six popular Density Functional Theory (DFT) calculation methods (B3LYP, B2PLYP, M06, M06-2X, omegaB97X, omegaB97XD), each combined with three different basis sets. The DFT enthalpy values are compared with five composite calculation methods (G3, G4, CBS QB3, CBS-APNO, W1U), and by CCSD(T)/aug-cc-pVTZ. Kinetic parameters are determined versus pressure and temperature for the unimolecular dissociation pathways of an oxiranyl radical, which include the chemical activation reactions of the ring-opened oxiranyl radical relative to the ring-opening barrier. Multifrequency quantum Rice Ramsperger Kassel (QRRK) analysis is used to determine k(E) with master equation analysis for falloff. The major overall reaction pathway at lower combustion temperatures is oxiranyl radical dissociation to a methyl radical and carbon monoxide. Oxiranyl radical dissociation to a ketene and hydrogen atom is the key reaction path above 700 K. PMID- 26990492 TI - Moth-Eye TiO2 Layer for Improving Light Harvesting Efficiency in Perovskite Solar Cells. AB - A moth-eye nanostructured mp-TiO2 film using conventional lithography, nano imprinting and polydimethyl-siloxane (PDMS) stamping methods is demonstrated for the first time. Power conversion efficiency of the moth-eye patterned perovskite solar cell is improved by ~11%, which mainly results from increasing light harvesting efficiency by structural optical property. PMID- 26990494 TI - Multicompartmental Microcapsules with Orthogonal Programmable Two-Way Sequencing of Hydrophobic and Hydrophilic Cargo Release. AB - Multicompartmental responsive microstructures with the capability for the pre programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual-responsive blocks (temperature for poly(N isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2 vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water-soluble hydrophilic macromolecules. For these dual-loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out-of-shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out-of-core release (pH). Reversing stimulus order completely alters the release process. PMID- 26990493 TI - Hypoxia-responsive miR-124 and miR-144 reduce hypoxia-induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing PIM1. AB - Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia-responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR-124 and miR-144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3'UTR of PIM1. Functional study showed that miR-124 or miR-144 overexpression can inhibit hypoxia-induced autophagy and enhance radiosensitivity at least via downregulating PIM1. Therefore, hypoxia induced miR-124 and miR-144 downregulation may contribute to a prosurvival mechanism of prostate cancer cells to hypoxia and irradiation at least through attenuated suppressing of PIM1. This finding presents a potential therapeutic target for prostate cancer. PMID- 26990496 TI - Cordoniform morphea: a clinicopathologic study of two cases presenting with the rope sign. AB - BACKGROUND: Morphea clinically presenting as cordoniform lesions has not been described previously in the literature. OBJECTIVE: Our goal was to describe the clinicopathologic features of morphea presenting with cord-like cutaneous lesions. METHODS: The clinical notes of 420 patients with a diagnosis of morphea seen during the previous 10 years were reviewed to identify any cases that had cordoniform lesions at presentation. RESULTS: Two adult patients (one male and one female) were identified. Both patients presented with chronic, slightly burning, bilateral, erythematous, linear or curvilinear elevated cutaneous indurations on the lateral chest wall strikingly reminiscent interstitial granulomatous dermatitis with arthritis. Histopathologically, typical changes of deep morphea with a band-like involvement only of the lower part of the reticular dermis and the superficial hypodermis and a remarkable perineural arrangement of the lymphoplasmocytic infiltrate were observed. The presence of Borrelia in skin biopsy samples of both patients was shown by immunohistochemistry and focus floating microscopy. In one patient, the presence of Borrelia afzelii DNA in the cutaneous biopsy was shown by polymerase chain reaction. CONCLUSIONS: Cordoniform morphea is an exceedingly unusual and previously undescribed clinicopathologic presentation of morphea where Borrelia infection may play a causal role. PMID- 26990495 TI - Characterization of the teosinte transcriptome reveals adaptive sequence divergence during maize domestication. AB - Annual teosinte, the ancestor of cultivated maize (Zea mays ssp. mays), is a valuable germplasm for enhancing the genetic diversity and adaptability of maize to various environment stimuli. However, comprehensive transcriptomic and genomic resources are unavailable in public databases, which significantly impede the identification and utilization of favourable genes or alleles in teosinte. In this study, we globally sequenced the transcriptomes of six teosinte accessions by Illumina paired-end sequencing. A high-quality teosinte transcriptome was de novo assembled with an average length of 770 bp and 63.99% of annotated unigenes. We found approximately 75% of the genes were highly conserved between maize and teosinte. Moreover, we also found 1516 unigenes were specifically expressed in teosinte, of which 84 unigenes were supported by gene models of four plant species, and 571 unigenes were located in the intergenic regions of maize genome, showing evidence-based expressed presence/absence variations (ePAVs). Furthermore, we also identified 99 unigenes with strong selection signals and 57 unigenes with >1 Ka/Ks ratios, suggesting that these genes might be under strong selection during maize domestication and improvement. Additionally, 11 286 teosinte unigene-derived primer pairs were developed for amplifying simple sequence repeat (SSR) loci. This study provides a comprehensive transcriptome of teosinte, a subset of genes that are highly conserved or diverged during maize domestication and improvement, and a massive set of available SSR primer pairs. These results facilitate the investigation of the comparative genomics and molecular domestication of teosinte and the utilization of teosinte germplasm for maize improvement. PMID- 26990497 TI - Material Exhibiting Efficient CO2 Adsorption at Room Temperature for Concentrations Lower Than 1000 ppm: Elucidation of the State of Barium Ion Exchanged in an MFI-Type Zeolite. AB - Carbon dioxide (CO2) gas is well-known as a greenhouse gas that leads to global warming. Many efforts have been made to capture CO2 from coal-fired power plants, as well as to reduce the amounts of excess CO2 in the atmosphere to around 400 ppm. However, this is not a simple task, particularly in the lower pressure region than 1000 ppm. This is because the CO2 molecule is chemically stable and has a relatively low reactivity. In the present study, the CO2 adsorption at room temperature on MFI-type zeolites exchanged with alkaline-earth-metal ions, with focus on CO2 concentrations <1000 ppm, was investigated both experimentally and by calculation. These materials exhibited a particularly efficient adsorption capability for CO2, compared with other presented samples, such as the sodium form and transition-metal ion-exchanged MFI-type zeolites. Ethyne (C2H2) was used as a probe molecule. Analyses were carried out with IR spectroscopy and X-ray absorption, and provided significant information regarding the presence of the M(2+)-O(2-)-M(2+) (M(2+): alkaline-earth-metal ion) species formed in the samples. It was subsequently determined that this species acts as a highly efficient site for CO2 adsorption at room temperature under very low pressure, compared to a single M(2+) species. A further advantage is that this material can be easily regenerated by a treatment, e.g., through the application of the temperature swing adsorption process, at relatively low temperatures (300-473 K). PMID- 26990498 TI - Announcing changes to randomized controlled trial (RCT) registration requirements and our new Short Report format. PMID- 26990499 TI - Effects of an Enhanced Recovery After Surgery programme on emergency surgical patients. AB - BACKGROUND: Enhanced Recovery After Surgery (ERAS) programmes have been used in elective surgery since the 1990s to optimize peri-operative care, reducing post operative complications, length of stay and overall costs. Following the local introduction of an ERAS programme for colorectal elective patients, it was suggested an increase in the use of ERAS-type principles in emergency patients may have occurred. The aims of this study were to determine whether management changes could be demonstrated and if there was a difference in outcomes. METHOD: A retrospective cohort study comparing emergency patients undergoing major abdominal surgery October 2008 to May 2010 (pre-ERAS) and January 2011 to December 2012 (post-ERAS) was performed. Details collected included admission and operative details, post-operative management and outcomes. RESULTS: A total of 370 patients were studied. Baseline variables were comparable. Post-ERAS, intra operative (P < 0.001) and post-operative 48 h totals (P < 0.001) of intravenous fluids were significantly reduced. Significantly fewer patients in the post-ERAS group had a catheter (P < 0.001), drain (P = 0.001) and patient controlled analgesia (P = 0.01) for more than two days. Major complications (P = 0.002) and individual minor complications such as urinary tract infections (P = 0.02), urinary retention (P = 0.001) and chest infections (P = 0.001) were all significantly reduced in the post-ERAS period. CONCLUSION: This study demonstrates a significant change in management towards ERAS principles in emergency patients following the introduction of such a programme in elective patients. The lack of increased complications in the second period suggests the use of ERAS principles is not harmful. The wider application of ERAS principles could improve outcomes in emergency surgery and deserves further study. PMID- 26990500 TI - Molybdenum Speciation and its Impact on Catalytic Activity during Methane Dehydroaromatization in Zeolite ZSM-5 as Revealed by Operando X-Ray Methods. AB - Combined high-resolution fluorescence detection X-ray absorption near-edge spectroscopy, X-ray diffraction, and X-ray emission spectroscopy have been employed under operando conditions to obtain detailed new insight into the nature of the Mo species on zeolite ZSM-5 during methane dehydroaromatization. The results show that isolated Mo-oxo species present after calcination are converted by CH4 into metastable MoCx Oy species, which are primarily responsible for C2 Hx /C3 Hx formation. Further carburization leads to MoC3 clusters, whose presence coincides with benzene formation. Both sintering of MoC3 and accumulation of large hydrocarbons on the external surface, evidenced by fluorescence-lifetime imaging microscopy, are principally responsible for the decrease in catalytic performance. These results show the importance of controlling Mo speciation to achieve the desired product formation, which has important implications for realizing the impact of CH4 as a source for platform chemicals. PMID- 26990501 TI - flowClean: Automated identification and removal of fluorescence anomalies in flow cytometry data. AB - Modern flow cytometry systems can be coupled to plate readers for high-throughput acquisition. These systems allow hundreds of samples to be analyzed in a single day. Quality control of the data remains challenging, however, and is further complicated when a large number of parameters is measured in an experiment. Our examination of 29,228 publicly available FCS files from laboratories worldwide indicates 13.7% have a fluorescence anomaly. In particular, fluorescence measurements for a sample over the collection time may not remain stable due to fluctuations in fluid dynamics; the impact of instabilities may differ between samples and among parameters. Therefore, we hypothesized that tracking cell populations (which represent a summary of all parameters) in centered log ratio space would provide a sensitive and consistent method of quality control. Here, we present flowClean, an algorithm to track subset frequency changes within a sample during acquisition, and flag time periods with fluorescence perturbations leading to the emergence of false populations. Aberrant time periods are reported as a new parameter and added to a revised data file, allowing users to easily review and exclude those events from further analysis. We apply this method to proof-of-concept datasets and also to a subset of data from a recent vaccine trial. The algorithm flags events that are suspicious by visual inspection, as well as those showing more subtle effects that might not be consistently flagged by investigators reviewing the data manually, and out-performs the current state of-the-art. flowClean is available as an R package on Bioconductor, as a module on the free-to-use GenePattern web server, and as a plugin for FlowJo X. (c) 2016 International Society for Advancement of Cytometry. PMID- 26990502 TI - Patterns of self-monitoring of blood glucose in insulin-treated diabetes: analysis of a Scottish population over time. AB - Analysis of a diabetes clinical information system in Tayside, Scotland, shows that a significant proportion of insulin-treated patients with diabetes are not self-monitoring blood glucose according to current clinical guidance and recommendations, with some not self-monitoring their blood glucose at all. Although there has been an increase in the number of reagent strips dispensed over the past decade, this increase is mainly accounted for by increased testing frequency among people with diabetes already testing. PMID- 26990503 TI - Validation of feasibility and quality of chicken breast meat cooked under various water-cooking conditions. AB - Under laboratory conditions, the qualities of boneless chicken breasts are commonly determined by placing them in a bag and cooking them in a water bath. The results are often applied as references for comparing the influences of cooking techniques. However, whether a sample cooked under this "laboratory" condition actually represents the meat cooked under the "real-life" condition in which meat is frequently cooked directly in water without packaging remains unclear. Whether the two cooking conditions lead to comparable results in meat quality should be determined. This study evaluated the influence of cooking conditions, including "placed-in-bag and cooked in a water bath (BC)" and "cooked directly in hot water (WC)" conditions, on the quality of chicken meat. The results reveal that BC samples had a longer cooking time. Deboned-and-skinless BC samples had a higher cooking loss and lower protein solubility (P < 0.01). BC samples with bone and skin had a higher lightness in both skin and muscle. No significant differences were observed in attributes, including shear force, collagen solubility, microstructures, redness, yellowness and descriptive sensory characteristics between treatments. Based on the results, considering the quality attributes that might be influenced, is critical when conducting relevant research. PMID- 26990504 TI - High Current Ionic Diode Using Homogeneously Charged Asymmetric Nanochannel Network Membrane. AB - A high current ionic diode is achieved using an asymmetric nanochannel network membrane (NCNM) constructed by soft lithography and in situ self-assembly of nanoparticles with uniform surface charge. The asymmetric NCNM exhibits high rectified currents without losing a rectification ratio because of its ionic selectivity gradient and differentiated electrical conductance. Asymmetric ionic transport is analyzed with diode-like I-V curves and visualized via fluorescent dyes, which is closely correlated with ionic selectivity and ion distribution according to variation of NCNM geometries. PMID- 26990506 TI - Endometrial Samples From Postmenopausal Women: A Proposal for Adequacy Criteria. AB - Approximately 75% of endometrial cancer occurs in women older than 55 yr of age. Postmenopausal bleeding is often considered endometrial cancer until proven otherwise. One diagnostic challenge is that endometrial biopsy or curettage generally yields limited samples from elderly patients. There are no well-defined and unified diagnostic criteria for adequacy of endometrial samples. Pathologists who consider any sample including those lacking endometrial tissue as "adequate" run the risk of rendering false-negative reports; on the contrary, pathologists requiring ample endometrial glands along with stroma tend to designate a greater number of samples as "inadequate," leading to unnecessary follow-up. We undertook a quantitative study of 1768 endometrial samples from women aged 60 yr and older aiming to propose validated adequacy criteria for diagnosing or excluding malignancy. Using repeat-procedure outcomes as reference, we found that samples exceeding 10 endometrial strips demonstrated high negative predictive value close to 100%. Such samples can be scant, yet appear to be sufficient in excluding malignant conditions. When tissue diminished to <10 strips, negative predictive value dropped significantly to 81%. The risk of undersampled malignancy rose to 19%. Among 274 malignant cases, only 4 cases yielded limited tissue yet >10 strips. In conclusion, we propose 10 endometrial strips as the minimum for adequate samples from postmenopausal women. Applying such validated adequacy criteria will greatly reduce false-negative errors and avoid unnecessary procedures while ultimately improving diagnostic accuracy. Our criteria may serve as a reference point in unifying the pathology community on this important and challenging topic. PMID- 26990505 TI - Bias in food intake reporting in children and adolescents with type 1 diabetes: the role of body size, age and gender. AB - BACKGROUND: An assessment of total daily energy intake is helpful in planning the overall treatment of children with type 1 diabetes (T1D). However, energy intake misreporting may hinder nutritional intervention. AIMS: To assess the plausibility of energy intake reporting and the potential role of gender, body mass index (BMI) z-score (z-BMI), disease duration and insulin requirement in energy intake misreporting in a sample of children and adolescents with T1D. METHODS: The study included 58 children and adolescents aged 8-16 yr with T1D. Anthropometry, blood pressure and glycated hemoglobin (HbA1c) were measured. Subjects were instructed to wear a SenseWear Pro Armband (SWA) for 3 consecutive days, including a weekend day and to fill out with their parents a weighed dietary record for the same days. Predicted energy expenditure (pEE) was calculated by age and gender specific equations, including gender, age, weight, height and physical activity level (assessed by SWA). The percent reported energy intake (rEI)/pEE ratio was used as an estimate of the plausibility of dietary reporting. RESULTS: Misreporting of food intake, especially under-reporting, was common in children and adolescents with T1D: more than one-third of participants were classified as under-reporters and 10% as over-reporters. Age, z-BMI and male gender were associated with the risk of under-reporting (model R2 = 0.5). Waist circumference was negatively associated with the risk of over-reporting (model R2 = 0.25). CONCLUSIONS: Children and adolescents with T1D frequently under-report their food intake. Age, gender and z-BMI contribute to identify potential under reporters. PMID- 26990507 TI - Cutaneous macroglobulinosis: successful treatment with rituximab. PMID- 26990508 TI - A new 3D-printed overtube system for endoscopic submucosal dissection: first results of a randomized study in a porcine model. AB - BACKGROUND AND STUDY AIM: Endoscopic therapy of early malignant alterations can be difficult and cumbersome. Our research study group took advantage of new methods for rapid prototyping (i. e. 3D printing) to design and test an overtube system with two manipulator arms at the tip. Both arms can be steered independently from each other by a dedicated user platform. METHODS: This animal study involved a randomized evaluation of the new overtube device for endoscopic submucosal dissection (ESD) compared with a conventionally performed ESD. In total, 12 ESDs in six pigs were performed. Six ESDs were performed in the stomach and six in the colon. Size (in cm(2)) of resected specimens, the time needed to perform endoscopic resection, and adverse events were assessed. RESULTS: The overtube-assisted ESD was faster and therefore more effective than the conventional ESD technique (0.45 +/- 0.24 cm(2)/min vs. 0.22 +/- 0.11 cm(2)/min; P = 0.029). Only one adverse effect was recorded in the conventional group. CONCLUSIONS: The overtube-assisted ESD was feasible in an animal model. ESD can be performed more quickly and potentially more effectively with the newly designed overtube device compared with the conventional ESD technique. PMID- 26990509 TI - Early precut sphincterotomy for difficult biliary access to reduce post-ERCP pancreatitis: a randomized trial. AB - BACKGROUND AND STUDY AIM: Precut sphincterotomy is a technique usually employed for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of bile duct disease. It is a validated risk factor for post-ERCP pancreatitis (PEP), but it is not clear whether the risk is related to the technique itself or to the repeated biliary cannulation attempts preceding it. The primary aim of the study was to assess the incidence of PEP in early precut compared with the standard technique in patients with difficult biliary cannulation. Secondary aims were to compare complications and cannulation success. PATIENTS AND METHODS: In this prospective, multicenter, randomized, clinical trial, patients who were referred for therapeutic biliary ERCP and difficult biliary cannulation were randomized to early precut (Group A) or repeated papillary cannulation attempts followed, in cases of failure, by late precut (Group B). PEP was defined as the onset of upper abdominal pain associated with an elevation in serum pancreatic enzymes of at least three times the normal level at more than 24 hours after the procedure. No rectal indomethacin or diclofenac was used for prevention of PEP. RESULTS: A total of 375 patients were enrolled. PEP developed in 10 of the 185 patients (5.4 %) in Group A and 23 of the 190 (12.1 %) in Group B (odds ratio [OR] 0.35; 95 % confidence interval [CI] 0.16 - 0.78). The incidence of PEP was significantly lower in the early precut group (10/185, 5.4 %) than in the delayed precut subgroup (19/135 [14.1 %]; OR 0.42, 95 %CI 0.17 - 1.07). There were no differences in biliary cannulation success rates, bleeding, perforation, and cholangitis. CONCLUSIONS: In patients with difficult biliary cannulation, early precut is an effective technique and can significantly reduce the incidence of PEP. Repeated biliary cannulation attempts are a real risk factor for this complication. PMID- 26990512 TI - Assessing the effects of a sexually transmitted disease educational intervention on fraternity and sorority members' knowledge and attitudes toward safe sex behaviors. AB - BACKGROUND AND PURPOSE: College years are a time young adults examine high-risk sexual behaviors, increasing their risk for sexually transmitted diseases (STDs). Fraternity/sorority membership has been identified as one factor contributing to increased risky sexual behavior in college students. This study measured the effectiveness of an educational intervention targeting STD prevention in fraternity and sorority members, and examined relationships between STD knowledge, attitudes, and demographics. METHODS: A descriptive, correlational design was used. Pre- and posttest data were collected from fraternity and sorority members (N = 132). Instruments measured demographic characteristics, STD knowledge, and attitudes toward safe sex behaviors. CONCLUSIONS: There was a significant increase in STD knowledge from baseline (M = 13.03, SD = 6.5) to 1 week (M = 20.27, SD = 4.9) t (131) = -13.53, p = .000. Males were more likely to report attitudes toward risky sexual behavior rs(132) = .323, p = .000, and as knowledge increased, attitudes became more favorable to safe sex behaviors (pre STD knowledge and preintervention attitudes, r(132) = -.249, p = .004; post-STD knowledge and postintervention attitudes, rs(132) = -.307, p = .000). IMPLICATIONS FOR PRACTICE: Results support that brief STD educational interventions can increase STD knowledge. College health centers must aim to provide sexual health education to all students at every visit. PMID- 26990510 TI - Feasibility and safety of endoscopic submucosal dissection for lesions involving the ileocecal valve. AB - BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) has been applied to treat early colorectal cancers. The aim of this study was to clarify the clinical course of ESD for lesions involving the ileocecal valve (ICV) by evaluating the successful resection rates, and the risk and frequency of adverse events. PATIENTS AND METHODS: The outcome of ESD on 38 ICV lesions was compared with the outcome of 132 cecal lesions that did not involve the ICV or appendiceal orifice during the same study period. The factors related to longer procedure time, postoperative stricture development, and tumor recurrence were investigated for ESD of ICV lesions. RESULTS: There was no significant difference between the ICV and non-ICV groups in the en block resection rates. The median procedure time was significantly longer in the ICV group than in the non-ICV group, with a point estimate of the difference of 37 minutes (95 % confidence interval [CI] 20.00 to 56.00; P < 0.01). None of the patients developed symptomatic post-ESD stricture or tumor recurrence. ESD procedure duration was >= 120 minutes in 16 lesions and < 120 minutes in 22 lesions of the ICV group. A specimen diameter of >= 40 mm and tumor extension into terminal ileum were factors related to a longer procedure time (odds ratio [OR] 8.40, 95 %CI 1.53 to 46.10, P = 0.01; OR 10.60, 95 %CI 2.17 to 51.40, P < 0.01, respectively). CONCLUSIONS: ICV lesions can be resected by ESD without major adverse events or causing symptomatic stricture development. However, ESD for ICV lesions should be performed only by expert endoscopists, as the procedure requires accomplished endoscopic skill and experience. PMID- 26990513 TI - Activated Dissociation of HCl on Au(111). AB - We report zero-coverage reaction probabilities (S0) for HCl dissociative adsorption on Au(111) obtained by the seeded molecular beam hot-nozzle method. For measurements at normal incidence with mean translational energies ranging from 0.94 to 2.56 eV (nozzle temperatures 296 to 1060 K), S0 increased from 6 * 10(-6) to 2 * 10(-2). S0 also increased with increasing nozzle temperature for fixed incidence energy associated with the motion normal to the surface. Accounting for the influence of the vibrational state population and translational energy distributions in the incident beam, we are able to compare the experimental results to recent theoretical predictions. These calculations, performed employing 6-D quantum dynamics on an electronically adiabatic potential energy surface obtained using density functional theory at the level of the generalized gradient approximation and the static surface approximation, severely overestimate the reaction probabilities when compared with our experimental results. We discuss some possible reasons for this large disagreement. PMID- 26990514 TI - First Report on Vancomycin-Resistant Staphylococcus aureus in Bovine and Caprine Milk. AB - The present investigation was carried out to study the vancomycin resistance pattern of Staphylococcus aureus isolates (n = 274) obtained from 352 milk samples of bovine (269) and caprine (63) clinical and subclinical mastitis from different districts of West Bengal, India. Of them, seven isolates (vancomycin resistant S. aureus [VRSA] 1-7) exhibited resistance to vancomycin. Minimum inhibitory concentration of vancomycin (MICvan) for VRSA2 and VRSA3 was >=16 MUg/ml; thus categorized as VRSA. For rest of the isolates, MICvan was 8 MUg/ml and they were grouped as vancomycin intermediate S. aureus (VISA). Even though all the isolates were resistant to cefoxitin and oxacillin and possessed mecA gene, none of them carried vancomycin resistance gene. Furthermore, all the seven isolates were subjected to Staphylococcal cassette chromosome mec (SCCmec) typing, Staphylococcal protein A (spa) typing, and enterobacterial repetitive intergenic consensus polymerase chain reaction. All the isolates except VRSA3 and VRSA4 from Kolkata district exhibited diverse genetic lineage, irrespective of their host and antibiotic resistance pattern. These two isolates showed clonal similarity (MRSA-SCCmec-V-spa t267) with methicillin-resistant S. aureus (MRSA) strains previously reported in human and animal infection. Isolation of VRSA and VISA could probably be due to intensive use of vancomycin in healthcare premises, which might have led to the development of glycopeptide-resistant strains and thereafter, further disseminated in the environment, including livestock farms. Detection of VRSA in milk is a serious concern as it may further cause health problems in the consumers. This is the first ever report of VRSA in food animals, even though the pathogen is otherwise prevalent in humans. PMID- 26990515 TI - Long-Term Evaluation of Biotronik Linox and Linox(smart) Implantable Cardioverter Defibrillator Leads. AB - INTRODUCTION: Expert consensus holds that post-market, systematic surveillance of ICD leads is essential to ensure confirmation of adequate lead performance. GALAXY (NCT00836589) and CELESTIAL (NCT00810264) are ongoing multicenter, prospective, non-randomized registries conducted to confirm the long-term safety and reliability of Biotronik leads. METHODS AND RESULTS: ICD and CRT-D patients are followed for Linox and Linox(smart) ICD lead performance and safety for 5 years post-implant. All procedural and system-related adverse events (AEs) were assessed at each follow-up, along with lead electrical parameters. An independent CEC of EPs adjudicated AEs to determine AE category and lead relatedness. The analysis used categories of lead observations per ISO 5841-2 (Third edition). A total of 3,933 leads were implanted in 3,840 patients (73.0% male, mean age 67.0 +/- 12.2 years) at 146 US centers. The estimated cumulative survival probability was 96.3% at 5 years after implant for Linox leads and 96.6% at 4 years after implant for Linox(smart) leads. A comparison of the Linox and Linox(smart) survival functions did not find evidence of a difference (P = 0.2155). The most common AEs were oversensing (23, 0.58%), conductor fracture (14, 0.36%), failure to capture (13, 0.33%), lead dislodgement (12, 0.31%), insulation breach (10, 0.25%), and abnormal pacing impedance (8, 0.20%). CONCLUSIONS: Linox and Linox(smart) ICD leads are safe, reliable and infrequently associated with lead related AEs. Additionally, estimated cumulative survival probability is clinically acceptable and well within industry standards. Ongoing data collection will confirm the longer-term safety and performance of the Linox family of ICD leads. PMID- 26990517 TI - Large Diversity of Porcine Yersinia enterocolitica 4/O:3 in Eight European Countries Assessed by Multiple-Locus Variable-Number Tandem-Repeat Analysis. AB - A total of 253 multiple-locus variable-number tandem-repeat analysis (MLVA) types among 634 isolates were discovered while studying the genetic diversity of porcine Yersinia enterocolitica 4/O:3 isolates from eight different European countries. Six variable-number tandem-repeat (VNTR) loci V2A, V4, V5, V6, V7, and V9 were used to study the isolates from 82 farms in Belgium (n = 93, 7 farms), England (n = 41, 8 farms), Estonia (n = 106, 12 farms), Finland (n = 70, 13 farms), Italy (n = 111, 20 farms), Latvia (n = 66, 3 farms), Russia (n = 60, 10 farms), and Spain (n = 87, 9 farms). Cluster analysis revealed mainly country specific clusters, and only one MLVA type consisting of two isolates was found from two countries: Russia and Italy. Also, farm-specific clusters were discovered, but same MLVA types could also be found from different farms. Analysis of multiple isolates originating either from the same tonsils (n = 4) or from the same farm, but 6 months apart, revealed both identical and different MLVA types. MLVA showed a very good discriminatory ability with a Simpson's discriminatory index (DI) of 0.989. DIs for VNTR loci V2A, V4, V5, V6, V7, and V9 were 0.916, 0.791, 0.901, 0.877, 0.912, and 0.785, respectively, when studying all isolates together, but variation was evident between isolates originating from different countries. Locus V4 in the Spanish isolates and locus V9 in the Latvian isolates did not differentiate (DI 0.000), and locus V9 in the English isolates showed very low discriminatory power (DI 0.049). The porcine Y. enterocolitica 4/O:3 isolates were diverse, but the variation in DI demonstrates that the well discriminating loci V2A, V5, V6, and V7 should be included in MLVA protocol when maximal discriminatory power is needed. PMID- 26990516 TI - The design and synthesis of new synthetic low-molecular-weight heparins. AB - Low-molecular-weight heparin (LMWH) has remained the most favorable form of heparin in clinics since the 1990s owing to its predictable pharmacokinetic properties. However, LMWH is mainly eliminated through the kidney, which limits its use in renal-impaired patients. In addition, the anticoagulant activity of LMWH is only partially neutralized by protamine. LMWH is obtained from a full length, highly sulfated polysaccharide harvested from porcine mucosal tissue. The depolymerization involved in LMWH production generates a broad distribution of LMWH fragments (6-22 sugar residues). This, combined with the various methods used to produce commercial LMWHs, results in variable pharmacological and pharmacokinetic properties. An alternative chemoenzymatic approach offers a method for the synthesis of LMWH that has the potential to overcome the limitations of current LMWHs. This review summarizes the application of a chemoenzymatic approach to generate LMWH and the rationale for development of a synthetic LMWH. PMID- 26990518 TI - Rate and Predisposing Factors for Sacroiliac Joint Radiographic Progression After a Two-Year Follow-up Period in Recent-Onset Spondyloarthritis. AB - OBJECTIVE: To evaluate the rate of radiographic structural progression in the sacroiliac (SI) joints in patients with radiographic or nonradiographic axial spondyloarthritis (SpA), and to determine factors predisposing to such progression, over 2 years. METHODS: Patients with recent-onset axial SpA (from the Devenir des Spondyloarthropathies Indiffererenciees Recentes cohort) were assigned a radiographic SI joint score according to the modified New York criteria. Demographic characteristics, smoking status, HLA-B27 positivity, inflammation on magnetic resonance imaging (MRI) of the SI joints, disease activity, and treatment were investigated as potential predisposing factors. The main analysis consisted of the evaluation of the switch from nonradiographic to radiographic axial SpA, but other definitions of radiographic progression were also evaluated. RESULTS: Of the 708 patients enrolled, 449 had baseline and 2 year pelvic radiographs. Of these patients, 47% were men. Their mean +/- SD age was 34 +/- 9 years, 61% were B27 positive, and 37% had inflammation of the SI joints on MRI. The percentages of patients who switched from nonradiographic to radiographic axial SpA (4.9% [16 of 326]) and from radiographic to nonradiographic axial SpA (5.7% [7 of 123]) were low. The mean +/- SD change in the total SI joint score (range 0-8) was small (0.1 +/- 0.8) but highly significant (P < 0.001). The potential baseline predisposing factors for meeting the modified New York criteria in the multivariate analysis were current smoking, HLA-B27 positivity, and inflammation of the SI joints on MRI, with odds ratios of 3.3 (95% confidence interval [95% CI] 1.0-11.5], 12.6 (95% CI 2.3-274), and 48.8 (95% CI 9.3-904), respectively. CONCLUSION: Our findings suggest that structural progression does exist in early SpA, but it is quite small and observed in a small number of patients, and that environmental (smoking status), genetic (HLA B27 positivity), and inflammation (inflammation of the SI joints on MRI) markers might be independent predisposing factors for progression. PMID- 26990519 TI - Tools of the trade: studying molecular networks in plants. AB - Driven by recent technological improvements, genes can be now studied in a larger biological context. Genes and their protein products rarely operate as a single entity and large-scale mapping by protein-protein interactions can unveil the molecular complexes that form in the cell to carry out various functions. Expression analysis under multiple conditions, supplemented with protein-DNA binding data can highlight when genes are active and how they are regulated. Representing these data in networks and finding strongly connected sub-graphs has proven to be a powerful tool to predict the function of unknown genes. As such networks are gradually becoming available for various plant species, it becomes possible to study how networks evolve. This review summarizes currently available network data and related tools for plants. Furthermore we aim to provide an outlook of future analyses that can be done in plants based on work done in other fields. PMID- 26990521 TI - Rosacea: Diagnosis and management. PMID- 26990520 TI - 5-HT3 receptors promote colonic inflammation via activation of substance P/neurokinin-1 receptors in dextran sulphate sodium-induced murine colitis. AB - BACKGROUND AND PURPOSE: 5-HT (serotonin) regulates various physiological functions, both directly and via enteric neurons. The present study investigated the role of endogenous 5-HT and 5-HT3 receptors in the pathogenic mechanisms involved in colonic inflammation, especially in relation to substance P (SP) and the neurokinin-1 (NK1 ) receptor. EXPERIMENTAL APPROACH: The effects of 5-HT3 and NK1 receptor antagonists were examined in dextran sulphate sodium (DSS)-induced colitis in mice. Inflammatory mediator expression and the distribution of 5-HT3 and NK1 receptors were also determined. KEY RESULTS: Daily administration of ramosetron and ondansetron (5-HT3 antagonists) dose-dependently attenuated the severity of DSS-induced colitis and up-regulation of inflammatory mediator expression. Immunohistochemical analysis showed 5-HT3 receptors are mainly expressed in vesicular ACh transporter-positive cholinergic nerve fibres in normal colon. DSS increased the number of colonic nerve fibres that were double positive for 5-HT3 receptors and SP but not of those that were double positive for 5-HT3 receptors and vesicular ACh transporter. DSS increased colonic SP levels and SP-positive nerve fibres; these responses were attenuated by ramosetron. DSS-induced colitis and up-regulation of inflammatory mediators were attenuated by aprepitant, an NK1 antagonist. Immunohistochemical studies further revealed that DSS treatment markedly increased NK1 receptor expression in CD11b positive cells. CONCLUSIONS AND IMPLICATIONS: These findings indicate that the 5 HT/5-HT3 receptor and SP/NK1 receptor pathways play pathogenic roles in colonic inflammation. 5-HT acts via 5-HT3 receptors to up-regulate inflammatory mediators and promote colonic inflammation. These effects may be further mediated by activation of macrophage NK1 receptors via SP released from 5-HT3 receptor positive nerve fibres. PMID- 26990524 TI - Opening doors: The practice degree that changes practice. AB - This descriptive, qualitative research study describes the educational experience and preparation for future practice of the initial three cohorts of DNP graduates of a Northwest university. "Opening doors: The practice degree that changes practice" was the overarching theme identified. Five additional themes included students and faculty as colearners; explaining the DNP; thinking differently about practice; navigating the capstone; and building bonds/collegial connections. PMID- 26990525 TI - Assessing DNP impact using program evaluations to capture healthcare system change. AB - The doctor of nursing practice (DNP) degree was formalized in 2004. Data evaluating the impact of DNP-prepared nurses on individual patient care, population health, and healthcare system outcomes are limited. This article demonstrates how the DNP Essentials can be used to frame DNP program evaluation data. PMID- 26990527 TI - Fastest non-ionic azo dyes and transfer of their thermal isomerisation kinetics into liquid-crystalline materials. AB - Push-pull bithienylpyrrole-based azo dyes exhibit thermal isomerisation rates as fast as 1.4 MUs in acetonitrile at 298 K becoming, thus, the fastest neutral azo dyes reported so far. These remarkably low relaxation times can be transferred into liquid-crystalline matrices enabling light-triggered oscillations in the optical density of the final material up to 11 kHz under ambient conditions. PMID- 26990529 TI - Self-Powered Electronic Skin with Biotactile Selectivity. AB - Power-generating flexible thin films for facile detection of biotactile events are fabricated from patterned metal-graphene oxide biopaper. These tactile materials are mechanically robust with a consistent output of 1 V and high response rate of 20 Hz. It is demonstrated that the simple quadruple electronic skin sensitively and selectively recognizes nine spatial biotactile positions and can readily be expanded. PMID- 26990528 TI - Histone turnover and chromatin accessibility: Critical mediators of neurological development, plasticity, and disease. AB - In postmitotic neurons, nucleosomal turnover was long considered to be a static process that is inconsequential to transcription. However, our recent studies in human and rodent brain indicate that replication-independent (RI) nucleosomal turnover, which requires the histone variant H3.3, is dynamic throughout life and is necessary for activity-dependent gene expression, synaptic connectivity, and cognition. H3.3 turnover also facilitates cellular lineage specification and plays a role in suppressing the expression of heterochromatic repetitive elements, including mutagenic transposable sequences, in mouse embryonic stem cells. In this essay, we review mechanisms and functions for RI nucleosomal turnover in brain and present the hypothesis that defects in histone dynamics may represent a common mechanism underlying neurological aging and disease. PMID- 26990530 TI - Effects of pay resets following drug use on attendance and hours worked in a therapeutic workplace. AB - This secondary data analysis examined effects of an abstinence contingency on participation in a therapeutic workplace. Participants exposed to a pay reset after drug use did not differ in overall attendance from participants who were not exposed to a pay reset after drug use; however, they initially worked less after a pay reset than participants who did not receive a pay reset, and their attendance increased as their pay increased. Overall participation was not influenced by the abstinence contingency, but transient decreases in attendance occurred. PMID- 26990532 TI - Getting Back to Work: Cognitive Behavioral Predictors of Depressive Symptoms and Job Search Success. AB - OBJECTIVE: Little is known about how cognitive behavioral approaches to depression might explain functional impairments associated with the disorder, such as extended periods of unemployment. To address this issue, we examined 5 cognitive behavioral predictors of depressive symptom change and job search outcome. METHOD: Using a sample of 75 unemployed adults, we examined cognitive style, brooding, dysfunctional attitudes, avoidance, and cognitive behavioral (CB) skills as predictors of change in depressive symptoms, job search self efficacy, and receipt of a job offer over a 3-month period. RESULTS: CB skills predicted lower depressive symptoms and increased odds of having received a job offer at the follow-up. Brooding predicted change in job search self-efficacy, but not in the expected direction. CONCLUSION: CB skills appear to predict job search outcomes as well as depressive symptoms. We encourage future work examining how CB skills may affect depressive symptoms, job search behaviors, and other areas of functioning. PMID- 26990533 TI - The ABCD's of 5'-adenosine monophosphate-activated protein kinase and adrenoleukodystrophy. AB - This Editorial highlights a study by Singh and coworkers in the current issue of Journal of Neurochemistry, in which the authors present additional evidence that AMPKalpha1 is reduced in X-linked adrenoleukodystrophy (X-ALD). They make a case for increasing AMPKalpha1 activity for therapeutic purposes in this disease, and indicate how this goal may be achieved. Read the highlighted article 'Metformin induced mitochondrial function and ABCD2 up regulation in X-linked adrenoleukodystrophy involves AMP activated protein kinase' on page 86. PMID- 26990531 TI - CXCR5 is critically involved in progression of lupus through regulation of B cell and double-negative T cell trafficking. AB - The recruitment of immune cells to sites of tissue inflammation is orchestrated by chemokine/chemokine receptor networks. Among these, the CXCL13/CXCR5 axis is thought to be involved critically in systemic lupus erythematosus (SLE) and lupus nephritis pathogenesis. Beyond B cell abnormalities, another hallmark of SLE disease is the occurrence of aberrant T cell responses. In particular, double negative (DN) T cells are expanded in the peripheral blood of patients with SLE and in lupus-prone mice. DN T cells induce immunoglobulin production, secrete proinflammatory cytokines and infiltrate inflamed tissue, including kidneys. We aimed to investigate how CXCR5 deficiency changes immune cell trafficking in murine lupus. We therefore crossed CXCR5(-/-) mice with B6/lpr mice, a well established murine lupus model. B cell numbers and B cellular immune responses were diminished in CXCR5-deficient B6/lpr mice. In addition, we observed reduced accumulation of DN T cells in spleen and lymph nodes, paralleled by reduced splenomegaly and lymphadenopathy. In-vivo migration assays revealed reduced migration of CXCR5-deficient DN T cells into lymph nodes, and ex-vivo-activated CXCR5-deficient DN T cells failed to infiltrate kidneys of recipients. Moreover, DN T cells and B cells of CXCR5-deficient B6/lpr mice failed to migrate towards CXCL13 in vitro. We propose that CXCR5 is involved critically in B cell trafficking and germinal cell (GC) formation in murine lupus and in guiding pathogenic DN T cells into lymphoid organs and kidneys, and we therefore describe new pathomechanisms for the CXCL13/CXCR5 axis in SLE. PMID- 26990534 TI - Context Dependent Regulation of Human Phosphoenolpyruvate Carboxykinase Isoforms by DNA Promoter Methylation and RNA Stability. AB - Cytoplasmic and mitochondrial isoforms of phosphoenolpyruvate carboxykinase (PEPCK-C and PEPCK-M) regulate hepatic gluconeogenesis to control systemic glucose homeostasis. Transcriptional and post-transcriptional mechanisms may govern synthesis, maintenance and cooperative function of compartmentalized PEPCK enzymes. In a comparative analysis, we show that tumor cells consistently transcribe and translate higher levels of enzymatically active PEPCK-C than PEPCK M and both the isoforms were present at lower levels in normal fibroblasts. Unlike in PEPCK-M, absence of glucose reduced the PEPCK-C mRNA and protein levels only in HepG2 cells. Interestingly, isoflavone genistein significantly increased PEPCK-C mRNA and protein levels in normal fibroblasts indicating cell type specific control mechanisms. Genistein also significantly affected RNA stability of PEPCK-C but not PEPCK-M in HepG2 cells. This was due to the conserved and functional mRNA destabilizing AU rich sequences at the 3'-UTR region of PEPCK-C gene and was confirmed by luciferase reporter assays suggesting that glucose deprivation and genistein targets these sequences for mRNA degradation in HepG2 cells but not in fibroblasts. Analysis of promoter methylation by luciferase reporter assays and bisulfite DNA sequencing suggested that PEPCK-C but not PEPCK M promoter was activated by 5-aza-2-deoxycytidine by inducing cytosine demethylation at the specific CpG dinucleotides of 5'-UTR region. Taken together, our data suggests stable PEPCK-M activity and identifies intricate relationship between (1) mRNA stability and (2) promoter DNA methylation as two mechanisms of gene expression that distinguishes PEPCK-C and PEPCK-M enzyme activities in a context and cell type dependent manner during gluconeogenesis. J. Cell. Biochem. 117: 2506-2520, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990536 TI - The new Cutaneous Lymphoma International Prognostic index (CLIPi) for early mycosis fungoides failed to identify prognostic groups in a cohort of Spanish patients. PMID- 26990535 TI - miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia. AB - The biological basis of essential thrombocythemia (ET) patients lacking known mutations is still unknown. MicroRNAs (miRNA) regulate hematopoietic differentiation and are deregulated in several hematopoietic malignancies. However, miRNA expression in ET patients has been poorly explored. We performed miRNA profiling in platelets from 19 ET patients and 10 healthy controls. Hierarchical cluster analysis showed two well-separated clusters between patients and controls, indicating that ET platelets had a characteristic 70-miRNA signature (P<0.0001), 68 of which were downregulated. According to the mutational status, three differentially expressed miRNAs, miR-15a (P=0.045), miR-150 (P=0.001) and miR-519a (P=0.036), were identified. A 40-miRNA signature was identified characterizing JAK2V617F-positive ET patients. Eight genes, whose interaction with the miRNAs could activate the JAK/STAT pathway were identified. An inverse correlation was observed between miRNAs expression and their target genes for SOCS1 and miR-221, SOCS3 and miR-221, SOCS3 and miR-203, and PTPN11 and miR-23a. All three miRNAs were upregulated in JAK2V617F-negative ET patients. SOCS1 and SOCS3 were validated as targets of miR-221 and miR-203, respectively. In summary, our study shows that platelets from JAK2V617F-negative ET patients harbor a specific miRNA signature that can participate in the modulation of the JAK/STAT pathway through regulation of key genes as SOCS1 and SOCS3. PMID- 26990537 TI - Knockout of p11 attenuates the acquisition and reinstatement of cocaine conditioned place preference in male but not in female mice. AB - Cocaine's enhancement of dopamine signaling is crucial for its rewarding effects but its serotonergic effects are also relevant. Here we examined the role of the protein p11, which recruits serotonin 5HT1B and 5HT4 receptors to the cell surface, in cocaine reward. For this purpose we tested wild-type (WT) and p11 knockout (KO) male and female mice for cocaine conditioned place preference (CPP) and its cocaine-induced reinstatement at different abstinence times, after 8 days of extinction and 28 days of being home-caged. All mice showed significant cocaine CPP. Among males, p11KO showed lower CPP than WT; this difference was also evident after 28 days of home-cage abstinence. In contrast, in females there were no CPP differences between p11KO and WT mice at any time point tested. Cocaine priming after the 28-day home-cage abstinence period also resulted in lower cocaine conditioned motor activity in both male and female p11KO mice. These results suggest that cocaine CPP and its persistence during extinction and reinstatement are modulated in a sex-differentiated manner by p11. The lack of protein p11 confers protection from CPP on male, but not female mice, immediately after cocaine conditioning as well as after prolonged abstinence, but not after short-term withdrawal. Synapse 70:293-301, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990538 TI - Langerhans cell histiocytosis mimicking lichen nitidus with bone involvement. AB - We report the case of a 6-month-old Hispanic boy with a 4-month history of widespread pruritic hypopigmented papules mimicking lichen nitidus. The final diagnosis was multisystem non-risk-organ Langerhans cell histiocytosis (LCH), with cutaneous and multiple bone involvement. With this patient and others previously reported in the literature, we suggest an early biopsy of the hypopigmented rash in children. PMID- 26990539 TI - Discovery of a Novel, Orally Efficacious Liver X Receptor (LXR) beta Agonist. AB - This article describes the application of Contour to the design and discovery of a novel, potent, orally efficacious liver X receptor beta (LXRbeta) agonist (17). Contour technology is a structure-based drug design platform that generates molecules using a context perceptive growth algorithm guided by a contact sensitive scoring function. The growth engine uses binding site perception and programmable growth capability to create drug-like molecules by assembling fragments that naturally complement hydrophilic and hydrophobic features of the protein binding site. Starting with a crystal structure of LXRbeta and a docked 2 (methylsulfonyl)benzyl alcohol fragment (6), Contour was used to design agonists containing a piperazine core. Compound 17 binds to LXRbeta with high affinity and to LXRalpha to a lesser extent, and induces the expression of LXR target genes in vitro and in vivo. This molecule served as a starting point for further optimization and generation of a candidate which is currently in human clinical trials for treating atopic dermatitis. PMID- 26990540 TI - Electron tunneling in proteins program. AB - We developed a unique integrated software package (called Electron Tunneling in Proteins Program or ETP) which provides an environment with different capabilities such as tunneling current calculation, semi-empirical quantum mechanical calculation, and molecular modeling simulation for calculation and analysis of electron transfer reactions in proteins. ETP program is developed as a cross-platform client-server program in which all the different calculations are conducted at the server side while only the client terminal displays the resulting calculation outputs in the different supported representations. ETP program is integrated with a set of well-known computational software packages including Gaussian, BALLVIEW, Dowser, pKip, and APBS. In addition, ETP program supports various visualization methods for the tunneling calculation results that assist in a more comprehensive understanding of the tunneling process. (c) 2016 Wiley Periodicals, Inc. PMID- 26990541 TI - Acceptability and Reliability of a Novel Palliative Care Screening Tool Among Emergency Department Providers. AB - BACKGROUND: The Palliative Care and Rapid Emergency Screening (P-CaRES) Project is an initiative intended to improve access to palliative care (PC) among emergency department (ED) patients with life-limiting illness by facilitating early referral for inpatient PC consultations. In the previous two phases of this project, we derived and validated a novel PC screening tool. This paper reports on the third and final preimplementation phase. OBJECTIVES: Examine the acceptability of the P-CaRES tool among PC and ED providers as well as test its reliability on case vignettes. Compare variations in reliability and acceptability of the tool based on ED providers' roles (attendings, residents, and nurses) and lengths of experience. METHODS: A two-part electronic survey was distributed to ED providers at multiple sites across the United States. We tested the reliability of the tool in the first part of the survey, through a series of case vignettes. A criterion standard of correct responses was first defined by consensus input from expert PC physicians' interpretations of the vignettes. The experts' input was validated using the Gwet's AC1 coefficient for inter-rater reliability. ED providers were then presented with the case vignettes and asked to use the P-CaRES tool to correctly identify which patients had unmet PC needs. ED provider responses were compared both against the criterion standard and against different subsets of respondents (divided both by role and by level of experience). The second part of the survey assessed acceptability of the P-CaRES tool among ED providers using responses to questions from a modified Ottawa Acceptability of Decision Rules Instrument, based on a 1-5 Likert rating scale. Descriptive statistics were used to report all outcomes. RESULTS: In total, 213 ED providers employed in three different regions across the country responded to the survey (39.4%) and 185 (86.9%) of those completed it. The majority of providers felt that the tool would be useful in their practice (80.5%), agreed that the tool was clear and unambiguous (87.1%), thought that use of the tool would likely benefit patients (87.5%), and thought that it would result in improved use of resources to help severely ill patients (83.6%). Over three quarters of ED providers (78.5%) also self-reported that they refer patients with unmet PC needs less than 10% of the time, and only 10.8% of respondents believed that they are already utilizing an effective strategy to screen or refer patients to PC. Applying our P-CaRES tool to case vignettes, ED providers generated PC referrals in concordance with PC experts over 88.7% of the time (95% confidence interval = 86.4% to 90.6%), with an overall sensitivity of more than 90%. These results varied minimally regardless of the respondent's role in the ED or their level of experience. CONCLUSION: Screening by emergency medicine providers for unmet PC needs using a brief, novel, content-validated screening tool is acceptable and is also reliable when applied to case vignettes-regardless of provider role or experience. Clinical trial and further study are warranted and are currently under way. PMID- 26990542 TI - Multiple Stressor Differential Tolerances: Possible Implications at the Population Level. AB - The probability of the most sensitive genotypes being eliminated from a population due to a contaminant pulse--genetic erosion--is negatively associated to the within-genotype variation. A sensitive genotype with a small phenotypic variation would be more prone to be lost-a critically sensitive genotype. Furthermore, natural populations inhabiting contaminated sites are usually exposed to several pollutants. Such co- or sequential exposure can have severe effects if at least some tolerant clonal lineages surviving one contaminant are sensitive to the others. Such an inverse relationship coupled with a low within genotype variation potentially enhances genetic erosion. Accordingly, this study evaluated co-tolerance and the occurrence of clonal lineages critically sensitive to 48-hours lethal exposures of copper, zinc, cobalt, and chromium among eight clonal lineages of the cladocerans Daphnia longispina. Median lethal concentrations (LC50) of each metal were found to have the potential to provoke genetic erosion. Pairwise comparisons of LC50, from the eight clonal lineages, revealed neither negative nor positive correlations (r <= |0.56|; p >= 0.18), but inversely sensitive clonal lineages were found for all pairs of metals. Therefore, besides having the potential to eliminate critically sensitive clonal lineages in a first intermediately lethal pulse, all tested metals may provoke further losses of clonal lineages in an already genetically eroded population. PMID- 26990543 TI - Language modulation of benign essential blepharospasm. PMID- 26990544 TI - Congenital Uterine Anomalies and Uterine Rupture. AB - Congenital uterine anomalies are more common than previously recognized. While many women will have no symptoms or problems, some women with congenital uterine anomalies have increased risks of adverse outcomes during pregnancy. This article presents a case study of a woman with a congenital uterine anomaly leading to spontaneous rupture of her unscarred uterus remote from term. The most common types of congenital uterine anomalies and their associated reproductive risks are reviewed. Evaluation of congenital uterine anomalies and management alternatives are discussed. PMID- 26990545 TI - IL-12 and IL-4 activate a CD39-dependent intrinsic peripheral tolerance mechanism in CD8(+) T cells. AB - Immune responses to protein antigens involve CD4(+) and CD8(+) T cells, which follow distinct programs of differentiation. Naive CD8 T cells rapidly develop cytotoxic T-cell (CTL) activity after T-cell receptor stimulation, and we have previously shown that this is accompanied by suppressive activity in the presence of specific cytokines, i.e. IL-12 and IL-4. Cytokine-induced CD8(+) regulatory T (Treg) cells are one of several Treg-cell phenotypes and are Foxp3(-) IL-10(+) with contact-dependent suppressive capacity. Here, we show they also express high level CD39, an ecto-nucleotidase that degrades extracellular ATP, and this contributes to their suppressive activity. CD39 expression was found to be upregulated on CD8(+) T cells during peripheral tolerance induction in vivo, accompanied by release of IL-12 and IL-10. CD39 was also upregulated during respiratory tolerance induction to inhaled allergen and on tumor-infiltrating CD8(+) T cells. Production of IL-10 and expression of CD39 by CD8(+) T cells was independently regulated, being respectively blocked by extracellular ATP and enhanced by an A2A adenosine receptor agonist. Our results suggest that any CTL can develop suppressive activity when exposed to specific cytokines in the absence of alarmins. Thus negative feedback controls CTL expansion under regulation from both nucleotide and cytokine environment within tissues. PMID- 26990546 TI - Increase in NRAS mutant allele percentage during metastatic melanoma progression. AB - One-fifth of cutaneous melanomas have dominant gain-of-function mutations of the NRAS oncogene. We report the first two cases of increasing NRAS mutant allele frequency in melanoma metastases and show that the chromosomal mechanism of this homozygosity is an increased polysomy of chromosome 1. We observed an increase in NRAS mutant allele percentage (NRAS-MA%) in the metastatic melanoma progression from 2 patients with melanomas harbouring a NRAS mutation (p.Q61K in case 1 and p.Q61R in case 2). In case 1, we observed a NRAS-MA% increase from 18% within the first metastatic node to 81%, 92% and 85% respectively in the three subsequent metastases: lymph node, brain and subcutaneous metastases biopsied 1, 6 and 17 months, respectively, after the initial lymph node biopsy. In case 2, we observed an increase in NRAS-MA% from 40% within the primary melanoma to 63% within the metastatic lymph node. FISH analysis showed the same results in both cases: a frequent polysomy of chromosome 1 in metastasis samples with NRAS mutant allele percentage >60%, while most cells were disomic in the samples with well-balanced heterozygous mutations. The percentage of NRAS mutant allele may increase during metastatic progression and may be associated with chromosomal instability. Further studies are needed to evaluate the prognostic impact of the NRAS homozygous status and/or polyploidy in metastatic cutaneous melanomas. PMID- 26990547 TI - Correction: Potential Impacts of Future Warming and Land Use Changes on Intra Urban Heat Exposure in Houston, Texas. PMID- 26990548 TI - NGS-Based Assay for the Identification of Individuals Carrying Recessive Genetic Mutations in Reproductive Medicine. AB - Next-generation sequencing (NGS) has the capacity of carrier screening in gamete donation (GD) programs. We have developed and validated an NGS carrier-screening test (qCarrier test) that includes 200 genes associated with 368 disorders (277 autosomal recessive and 37 X-linked). Carrier screening is performed on oocyte donation candidates and the male partner of oocyte recipient. Carriers of X linked conditions are excluded from the GD program, whereas donors are chosen who do not carry mutations for the same gene/disease as the recipients. The validation phase showed a high sensitivity (>99% sensitivity) detecting all single-nucleotide variants, 13 indels, and 25 copy-number variants included in the validation set. A total of 1,301 individuals were analysed with the qCarrier test, including 483 candidate oocyte donors and 635 receptor couples, 105 females receiving sperm donation, and 39 couples seeking pregnancy. We identified 56% of individuals who are carriers for at least one genetic condition and 1.7% of female donors who were excluded from the program due to a carrier state of X linked conditions. Globally, 3% of a priori assigned donations had a high reproductive risk that could be minimized after testing. Genetic counselling at different stages is essential for helping to facilitate a successful and healthy pregnancy. PMID- 26990549 TI - Favorable prognosis in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia patients following hematopoietic stem cell transplantation. PMID- 26990550 TI - Screening Mammography for Free: Impact of Eliminating Cost Sharing on Cancer Screening Rates. AB - OBJECTIVES: To study the impact of eliminating cost sharing for screening mammography on mammography rates in a large Medicare Advantage (MA) health plan which in 2010 eliminated cost sharing in anticipation of the Affordable Care Act mandate. STUDY SETTING: Large MA health maintenance organization offering individual-subscriber MA insurance and employer-supplemented group MA insurance. STUDY DESIGN: We investigated the impact on breast cancer screening of a policy that eliminated a $20 copayment for screening mammography in 2010 among 53,188 women continuously enrolled from 2007 to 2012 in an individual-subscriber MA plan, compared with 42,473 women with employer-supplemented group MA insurance in the same health maintenance organization who had full screening coverage during this period. We used differences-in-differences analysis to study the impact of cost-sharing elimination on mammography rates. PRINCIPAL FINDINGS: Annual screening rates declined over time for both groups, with similar trends pre-2010 and a slower decline after 2010 among women whose copayments were eliminated. Among women aged 65-74 years in the individual-subscriber MA plan, 44.9 percent received screening in 2009 compared with 40.9 percent in 2012, while 49.5 percent of women in the employer-supplemented MA plan received screening in 2009 compared with 44.1 percent in 2012, that is, a difference-in-difference effect of 1.4 percentage points less decline in screening among women experiencing the cost sharing elimination. Effects were concentrated among women without recent screening. There were no differences by neighborhood socioeconomic status or race/ethnicity. CONCLUSIONS: Eliminating cost sharing for screening mammography was associated with modesty lower decline in screening rates among women with previously low screening adherence. PMID- 26990551 TI - Prevalence and Associated Factors for Dual Form of Malnutrition in Mother-Child Pairs at the Same Household in the Gaza Strip-Palestine. AB - BACKGROUND: In many developing countries nutritional, and epidemiological transitions are emerging into continuing undernutrition and escalating overnutrition, giving rise to the double burden of the malnutrition phenomenon. OBJECTIVES: This study aims to determine the prevalence of the dual form of malnutrition (overweight mother/underweight child) in the same household and its associated factors in the Gaza Strip. METHODS: A total of 357 mother-child pairs from the same households were surveyed from three different geographical locations in the Gaza Strip, namely, El Remal urban area, Jabalia refugee camp, and Al Qarara rural area. The height and weight of mothers aged 18-50 years were measured, and their body mass index (BMI) was computed. The mothers were categorized according to the criterion of the World Health Organization (WHO) for BMI as overweight if they have a BMI >= 25 kg/m2. Anthropometric indices were measured for children aged two to five years to classify the underweight children Z-score <-1. RESULTS: The results showed the prevalence of the dual form of malnutrition in the Gaza Strip was 15.7%, and its associated factors were child's birth order (ORadj, 1.50, 95% CL, 1.22, 1.82; p = <0.001), father's educational (low or medium) levels (ORadj, 3.19, 95% CL, 1.07, 9.5; p = 0. 036), or (ORadj, 3.4, 95% CL, 1.12, 10.37; p = 0. 031), high scores of mothers' nutrition knowledge (ORadj, 1.23, 95% CL, 1.01, 1.52; p = 0. 048), and low monthly income (ORadj, 0.28, 95% CL, 0.09, 0.88; p = 0. 030). CONCLUSIONS: The results from this study showed the dual form of malnutrition in the same household was prevalent in the Gaza Strip. This is a public health issue that must be understood and addressed and policy makers must implement an appropriate nutrition action plan to control dual form of malnutrition based on the underlying specific risk factors in the study population. In addition, interventions are needed to help individuals to translate their nutrition knowledge into healthy dietary behaviors. PMID- 26990552 TI - Sex sells,..... PMID- 26990553 TI - A multivariate cure model for left-censored and right-censored data with application to colorectal cancer screening patterns. AB - We develop a multivariate cure survival model to estimate lifetime patterns of colorectal cancer screening. Screening data cover long periods of time, with sparse observations for each person. Some events may occur before the study begins or after the study ends, so the data are both left-censored and right censored, and some individuals are never screened (the 'cured' population). We propose a multivariate parametric cure model that can be used with left-censored and right-censored data. Our model allows for the estimation of the time to screening as well as the average number of times individuals will be screened. We calculate likelihood functions based on the observations for each subject using a distribution that accounts for within-subject correlation and estimate parameters using Markov chain Monte Carlo methods. We apply our methods to the estimation of lifetime colorectal cancer screening behavior in the SEER-Medicare data set. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990555 TI - Fetal aorta larger than the main pulmonary artery on the three-vessel view: Correlation with postnatal echocardiographic findings. AB - PURPOSE: This study investigated postnatal cardiac anomalies determined by postnatal echocardiography in fetuses with the ascending aorta (AA) diameter larger than that of the main pulmonary artery (MPA) on the three-vessel view (3VV). METHODS: The study included 17 pregnancies. The diameters of the AA and MPA were assessed on the 3VV in second-trimester sonographic screening, and all the patients underwent postnatal echocardiography to assess the cardiac outcome. RESULTS: In the study population, the mean AA diameter was 3.7 mm (range, 2.2-5.6 mm), and the mean MPA diameter was 3.2 mm (range, 1.8-5.2 mm). The mean AA/MPA ratio was 1.2 (range, 1.1-1.9). According to the postnatal echocardiograms, one of the patients had tetralogy of Fallot. This patient had the highest prenatal AA/MPA ratio (1.9). Among the remaining 16 cases, five had secundum atrial septal defects, with two having concomitant dilatation of the AA. There was one case of isolated dilatation of the AA. CONCLUSIONS: Although an AA with a diameter larger than that of the MPA on the 3VV does not usually indicate severe congenital heart disease involving the ventricular outflow tract and/or great arteries, careful prenatal and postnatal echocardiographic examinations are mandatory to determine the presence of congenital heart disease. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:423-428, 2016. PMID- 26990556 TI - Anguilla japonica lectin 1 delivery through adenovirus vector induces apoptotic cancer cell death through interaction with PRMT5. AB - BACKGROUND: Our previous studies have demonstrated that, through adenovirus mediated gene delivery, various exogenously expressed lectins elicited cytotoxicity to cancer cells, utilizing protein arginine methyltransferase 5 (PRMT5) as a common binding target. METHODS: In the present study, a FLAG tagged Anguilla japonica lectin 1 (AJL1) expression cassette was genetically harbored in a replication-defective adenovirus genome, forming Ad.FLAG-AJL1. The exogenous AJL1-induced cytotoxicity and the underlying mechanisms were analyzed. RESULTS: The exogenous AJL1 suppressed the proliferation of a variety of human cancer cells by inducing apoptosis. Caspase 9, Bcl-2, X-linked inhibitor of apoptosis protein, mitogen-activated protein kinase kinase 1/2-extracellular signal regulated kinase and p38 mitogen-activated protein kinase were found to be responsible for the exogenous AJL1-induced cytotoxicity. AJL1 was further suggested to regulate PRMT5-E2F-1 pathway, a pathway shared by previously reported marine lectins Dicentrarchus labrax fucose binding lectin and Strongylocentrotus purpuratus rhamnose binding lectin. A localization study revealed that exogenous AJL1 widely distributed in the cell membrane and cytoplasm. CONCLUSIONS: The results of the present study suggest that the PRMT5 E2F-1 pathway may act as a common target for exogenous lectins including AJL1, and the cellular response to exogenous AJL1 may suggest a novel agent for cancer gene therapy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990554 TI - Streptococcus pneumoniae Cell-Wall-Localized Phosphoenolpyruvate Protein Phosphotransferase Can Function as an Adhesin: Identification of Its Host Target Molecules and Evaluation of Its Potential as a Vaccine. AB - In Streptococcus pneumonia, phosphoenolpyruvate protein phosphotransferase (PtsA) is an intracellular protein of the monosaccharide phosphotransferase systems. Biochemical and immunostaining methods were applied to show that PtsA also localizes to the bacterial cell-wall. Thus, it was suspected that PtsA has functions other than its main cytoplasmic enzymatic role. Indeed, recombinant PtsA and anti-rPtsA antiserum were shown to inhibit adhesion of S. pneumoniae to cultured human lung adenocarcinoma A549 cells. Screening of a combinatorial peptide library expressed in a filamentous phage with rPtsA identified epitopes that were capable of inhibiting S. pneumoniae adhesion to A549 cells. The insert peptides in the phages were sequenced, and homologous sequences were found in human BMPER, multimerin1, protocadherin19, integrinbeta4, epsin1 and collagen type VIIalpha1 proteins, all of which can be found in A549 cells except the latter. Six peptides, synthesized according to the homologous sequences in the human proteins, specifically bound rPtsA in the micromolar range and significantly inhibited pneumococcal adhesion in vitro to lung- and tracheal derived cell lines. In addition, the tested peptides inhibited lung colonization after intranasal inoculation of mice with S. pneumoniae. Immunization with rPtsA protected the mice against a sublethal intranasal and a lethal intravenous pneumococcal challenge. In addition, mouse anti rPtsA antiserum reduced bacterial virulence in the intravenous inoculation mouse model. These findings showed that the surface-localized PtsA functions as an adhesin, PtsA binding peptides derived from its putative target molecules can be considered for future development of therapeutics, and rPtsA should be regarded as a candidate for vaccine development. PMID- 26990557 TI - Highly Active and Robust Metalloporphyrin Catalysts for the Synthesis of Cyclic Carbonates from a Broad Range of Epoxides and Carbon Dioxide. AB - Bifunctional metalloporphyrins with quaternary ammonium bromides (nucleophiles) at the meta, para, or ortho positions of meso-phenyl groups were synthesized as catalysts for the formation of cyclic carbonates from epoxides and carbon dioxide under solvent-free conditions. The meta-substituted catalysts exhibited high catalytic performance, whereas the para- and ortho-substituted catalysts showed moderate and low activity, respectively. DFT calculations revealed the origin of the advantage of the meta-substituted catalyst, which could use the flexible quaternary ammonium cation at the meta position to stabilize various anionic species generated during catalysis. A zinc(II) porphyrin with eight nucleophiles at the meta positions showed very high catalytic activity (turnover number (TON)=240 000 at 120 degrees C, turnover frequency (TOF)=31 500 h(-1) at 170 degrees C) at an initial CO2 pressure of 1.7 MPa; catalyzed the reaction even at atmospheric CO2 pressure (balloon) at ambient temperature (20 degrees C); and was applicable to a broad range of substrates, including terminal and internal epoxides. PMID- 26990558 TI - A Photoresponsive Surface Covalent Organic Framework: Surface-Confined Synthesis, Isomerization, and Controlled Guest Capture and Release. AB - By introducing an azobenzene group to the backbone of diboronic acid, we have obtained a surface-confined, photoresponsive single-layer covalent organic framework with long-range order and almost entire surface coverage. Scanning tunneling microscopic characterization indicates that though the covalent linkage provides a significant locking effect, isomerization can still happen under UV irradiation, which causes destruction of the surface COF. Furthermore, the decomposed surface COF can recover upon annealing. This photoinduced decomposition provides a facile approach for the controlled capture and release of targeted objects using these nanoporous surface COFs as a host, which has been demonstrated in this work using copper phthalocyanine as a model guest. PMID- 26990559 TI - Rye-Based Evening Meals Favorably Affected Glucose Regulation and Appetite Variables at the Following Breakfast; A Randomized Controlled Study in Healthy Subjects. AB - BACKGROUND: Whole grain has shown potential to prevent obesity, cardiovascular disease and type 2 diabetes. Possible mechanism could be related to colonic fermentation of specific indigestible carbohydrates, i.e. dietary fiber (DF). The aim of this study was to investigate effects on cardiometabolic risk factors and appetite regulation the next day when ingesting rye kernel bread rich in DF as an evening meal. METHOD: Whole grain rye kernel test bread (RKB) or a white wheat flour based bread (reference product, WWB) was provided as late evening meals to healthy young adults in a randomized cross-over design. The test products RKB and WWB were provided in two priming settings: as a single evening meal or as three consecutive evening meals prior to the experimental days. Test variables were measured in the morning, 10.5-13.5 hours after ingestion of RKB or WWB. The postprandial phase was analyzed for measures of glucose metabolism, inflammatory markers, appetite regulating hormones and short chain fatty acids (SCFA) in blood, hydrogen excretion in breath and subjective appetite ratings. RESULTS: With the exception of serum CRP, no significant differences in test variables were observed depending on length of priming (P>0.05). The RKB evening meal increased plasma concentrations of PYY (0-120 min, P<0.001), GLP-1 (0-90 min, P<0.05) and fasting SCFA (acetate and butyrate, P<0.05, propionate, P = 0.05), compared to WWB. Moreover, RKB decreased blood glucose (0-120 min, P = 0.001), serum insulin response (0-120 min, P<0.05) and fasting FFA concentrations (P<0.05). Additionally, RKB improved subjective appetite ratings during the whole experimental period (P<0.05), and increased breath hydrogen excretion (P<0.001), indicating increased colonic fermentation activity. CONCLUSION: The results indicate that RKB evening meal has an anti-diabetic potential and that the increased release of satiety hormones and improvements of appetite sensation could be beneficial in preventing obesity. These effects could possibly be mediated through colonic fermentation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02093481. PMID- 26990561 TI - The Influence of Mark-Recapture Sampling Effort on Estimates of Rock Lobster Survival. AB - Five annual capture-mark-recapture surveys on Jasus edwardsii were used to evaluate the effect of sample size and fishing effort on the precision of estimated survival probability. Datasets of different numbers of individual lobsters (ranging from 200 to 1,000 lobsters) were created by random subsampling from each annual survey. This process of random subsampling was also used to create 12 datasets of different levels of effort based on three levels of the number of traps (15, 30 and 50 traps per day) and four levels of the number of sampling-days (2, 4, 6 and 7 days). The most parsimonious Cormack-Jolly-Seber (CJS) model for estimating survival probability shifted from a constant model towards sex-dependent models with increasing sample size and effort. A sample of 500 lobsters or 50 traps used on four consecutive sampling-days was required for obtaining precise survival estimations for males and females, separately. Reduced sampling effort of 30 traps over four sampling days was sufficient if a survival estimate for both sexes combined was sufficient for management of the fishery. PMID- 26990560 TI - Effects of Imidacloprid and Varroa destructor on survival and health of European honey bees, Apis mellifera. AB - There has been growing concern over declines in populations of honey bees and other pollinators which are a vital part to our food security. It is imperative to identify factors responsible for accelerated declines in bee populations and develop solutions for reversing bee losses. While exact causes of colony losses remain elusive, risk factors thought to play key roles are ectoparasitic mites Varroa destructor and neonicotinoid pesticides. The present study aims to investigate effects of a neonicotinoid pesticide Imidacloprid and Varroa mites individually on survivorship, growth, physiology, virus dynamics and immunity of honey bee workers. Our study provides clear evidence that the exposure to sublethal doses of Imidacloprid could exert a significantly negative effect on health and survival of honey bees. We observed a significant reduction in the titer of vitellogenin (Vg), an egg yolk precursor that regulates the honey bees development and behavior and often are linked to energy homeostasis, in bees exposed to Imidacloprid. This result indicates that sublethal exposure to neonicotinoid could lead to increased energy usage in honey bees as detoxification is a energy-consuming metabolic process and suggests that Vg could be a useful biomarker for measuring levels of energy stress and sublethal effects of pesticides on honey bees. Measurement of the quantitative effects of different levels of Varroa mite infestation on the replication dynamic of Deformed wing virus (DWV), an RNA virus associated with Varroa infestation, and expression level of immune genes yields unique insights into how honey bees respond to stressors under laboratory conditions. PMID- 26990562 TI - Comparison of latex body paint with wetted gauze wipes for sampling the chemical warfare agents VX and sulfur mustard from common indoor surfaces. AB - Comparison of solvent-wetted gauze with body paint, a peelable surface sampling media, for the sampling of the chemical warfare agents VX and sulfur mustard from nine surfaces was performed. The nine surfaces sampled are those typical of interior public venues and include smooth, rough, porous, and non-porous surfaces. Overall, solvent-wetted gauze (wipes) performed better for the recovery of VX from non-porous surfaces while body paint (BP) performed better for the porous surfaces. The average percent VX recoveries using wipes and BP, respectively, are: finished wood flooring, 86.2%, 71.4%; escalator handrail, 47.3%, 26.7%; stainless steel, 80.5%, 56.1%; glazed ceramic tile, 81.8%, 44.9%; ceiling tile, 1.77%, 13.1%; painted drywall 7.83%, 21.1%; smooth cement, 0.64%, 10.3%; upholstery fabric, 24.6%, 23.1%; unfinished wood flooring, 9.37%, 13.1%. Solvent-wetted gauze performed better for the recovery of sulfur mustard from three of the relatively non-porous surfaces while body paint performed better for the more porous surfaces. The average percent sulfur mustard recoveries using wipes and BP, respectively, are: finished wood flooring, 30.2%, 2.97%; escalator handrail, 4.40%, 4.09%; stainless steel, 21.2%, 3.30%; glazed ceramic tile, 49.7%, 16.7%; ceiling tile, 0.33%, 11.1%; painted drywall 2.05%, 10.6%; smooth cement, 1.20%, 35.2%; upholstery fabric, 7.63%, 6.03%; unfinished wood flooring, 0.90%, 1.74%. PMID- 26990563 TI - A study into the distribution of gunshot residue particles in the random population. AB - When considering the impact and value of gunshot residues (GSR) as forensic trace evidence, the likelihood of a suspect producing a positive GSR analysis result without having direct exposure to a firearm is a major consideration. Therefore, the random prevalence of GSR and 'GSR-like' residues in the wider population is a highly pertinent question when considering the probative value of such evidence. The random prevalence of GSR in two Australian jurisdictions - Victoria and South Australia - was assessed through the collection and analysis of GSR samples obtained from randomly selected members of the public. Volunteers were asked to declare any firearms use, hobbies or potential firearms exposure before allowing their hands to be sampled using aluminium GSR sample stubs coated in adhesive tape. A total of 289 samples, 120 from Victoria and 169 from South Australia were collected and analysed using scanning electron microscopy coupled with energy dispersive X-ray microanalysis (SEM-EDS). Across all samples, three 'characteristic' three-component Pb/Ba/Sb particles were detected from a single subject in South Australia, corresponding to an overall prevalence of 0.3%. Two component 'consistent' particles were more prevalent, with Pb/Sb particles being the most frequently occurring, in 8% of samples, and in South Australia only. A number of samples, approximately 7%, showed populations of single element particles of Pb, Ba and Sb, which has the potential to generate a false positive for GSR if using a bulk analysis technique such as NAA or AAS. The prevalence of GSR or 'GSR like' particles in this study matches closely with similar surveys conducted in other jurisdictions. Such surveys are a useful foundation for the creation of a probabilistic method for the assessment of GSR evidence. PMID- 26990564 TI - Technical note: The effects of Bluestar((r)) and luminol when used in conjunction with tetramethylbenzidine or phenolphthalein. AB - There are numerous presumptive tests available in the forensic science field to help identify the presence of blood. While many articles are available on the effects of Bluestar((r)) and luminol and potential interactions with subsequent DNA identification, the research field falls short in identifying the effects these two presumptive tests may have on subsequent presumptive tests used to help identify blood. To rectify this ongoing issue in the forensic science field, the chemiluminescence methods of Bluestar((r)) and luminol for the detection of blood at a crime scene were tested for their effects when used in conjunction with tetramethylbenzidine (TMB) or phenolphthalein (PT) at the forensic science laboratory. Six different substrates (untreated wood, pressure treated wood, ceramic tile, shag carpet, cement block, and cotton clothing) were stained with varying dilutions (range 1:1 to 1:100,000) of blood. Neither luminol nor Bluestar((r)) affect the results of PT or TMB tests at blood dilutions equal to or less than 1:100. However, interactions did occur between agents and substrates with blood dilutions 1:1000 or greater. Bluestar((r)) was the only presumptive test that can detect blood dilutions of 1:100,000 on some substrates and luminol was inclusive on pressure treated wood. These findings suggests that forensic science laboratory personal need to know and understand the details of how the blood was detected by the crime scene investigator and the substrate on which the blood was obtained from for their preparation of presumptive blood testing with PT or TMB. PMID- 26990566 TI - Official Development Assistance for reproductive health has increased but may not be going to those who need it the most. PMID- 26990565 TI - Prediction of (195) Pt NMR chemical shifts of dissolution products of H2 [Pt(OH)6 ] in nitric acid solutions by DFT methods: how important are the counter-ion effects? AB - (195) Pt NMR chemical shifts of octahedral Pt(IV) complexes with general formula [Pt(NO3 )n (OH)6 - n ](2-) , [Pt(NO3 )n (OH2 )6 - n ](4 - n) (n = 1-6), and [Pt(NO3 )6 - n - m (OH)m (OH2 )n ](-2 + n - m) formed by dissolution of platinic acid, H2 [Pt(OH)6 ], in aqueous nitric acid solutions are calculated employing density functional theory methods. Particularly, the gauge-including atomic orbitals (GIAO)-PBE0/segmented all-electron relativistically contracted-zeroth order regular approximation (SARC-ZORA)(Pt) ? 6-31G(d,p)(E)/Polarizable Continuum Model computational protocol performs the best. Excellent second-order polynomial plots of deltacalcd ((195) Pt) versus deltaexptl ((195) Pt) chemical shifts and deltacalcd ((195) Pt) versus the natural atomic charge QPt are obtained. Despite of neglecting relativistic and spin orbit effects the good agreement of the calculated delta (195) Pt chemical shifts with experimental values is probably because of the fact that the contribution of relativistic and spin orbit effects to computed sigma(iso) (195) Pt magnetic shielding of Pt(IV) coordination compounds is effectively cancelled in the computed delta (195) Pt chemical shifts, because the relativistic corrections are expected to be similar in the complexes and the proper reference standard used. To probe the counter-ion effects on the (195) Pt NMR chemical shifts of the anionic [Pt(NO3 )n (OH)6 - n ](2-) and cationic [Pt(NO3 )n (OH2 )6 - n ](4 - n) (n = 0-3) complexes we calculated the (195) Pt NMR chemical shifts of the neutral (PyH)2 [Pt(NO3 )n (OH)6 - n ] (n = 1-6; PyH = pyridinium cation, C5 H5 NH(+) ) and [Pt(NO3 )n (H2 O)6 - n ](NO3 )4 - n (n = 0-3) complexes. Counter-anion effects are very important for the accurate prediction of the (195) Pt NMR chemical shifts of the cationic [Pt(NO3 )n (OH2 )6 - n ](4 - n) complexes, while counter-cation effects are less important for the anionic [Pt(NO3 )n (OH)6 - n ](2-) complexes. The simple computational protocol is easily implemented even by synthetic chemists in platinum coordination chemistry that dispose limited software availability, or locally existing routines and knowhow. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990567 TI - Effects of motion segment level, Pfirrmann intervertebral disc degeneration grade and gender on lumbar spine kinematics. AB - MRI allows non-invasive assessment of intervertebral disc degeneration with the added clinical benefit of using non-ionizing radiation. What has remained unclear is the relationship between assessed disc degeneration and lumbar spine kinematics. Kinematic outcomes of 54 multi-segment (L1-Sacrum) lumbar spine specimens were calculated to discover if such an underlying relationship exists with degeneration assessed using the Pfirrmann grading system. Further analyses were also conducted to determine if kinematic outcomes were affected by motion segment level, gender or applied compressive preload. Range of motion, hysteresis, high flexibility zone size and rotational stiffness in flexion extension, lateral bending and axial rotation were the kinematic outcomes. Caudal intervertebral discs in our study sample were more degenerative than cranial discs. L5-S1 discs had the largest flexion-extension range of motion (p < 0.005) and L1-L2 discs the lowest flexion high flexibility zone size (p < 0.013). No other strict cranial-caudal differences in kinematic outcomes were found. Low flexibility zone rotational stiffness increased with disc degeneration grade in extension, lateral bending and axial rotation (p < 0.001). Trends towards higher hysteresis and lower range of motion with increased degeneration were observed in flexion-extension and lateral bending. Applied compressive preload increased flexion-extension hysteresis and augmented the effect of degeneration on hysteresis (p < 0.0005). Female specimens had about one degree larger range of motion in all rotational modes, and higher flexion extension hysteresis (p = 0.016). These results suggest that gender differences exist in lumbar spine kinematics. Additionally high disc loads, applied compressive preload or applied moment, are needed to kinematically distinguish discs with different levels of degeneration. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1389-1398, 2016. PMID- 26990568 TI - Recent mating-system evolution in Eichhornia is accompanied by cis-regulatory divergence. AB - The evolution of predominant self-fertilization from cross-fertilization in plants is accompanied by diverse changes to morphology, ecology and genetics, some of which likely result from regulatory changes in gene expression. We examined changes in gene expression during early stages in the transition to selfing in populations of animal-pollinated Eichhornia paniculata with contrasting mating patterns. We crossed plants from outcrossing and selfing populations and tested for the presence of allele-specific expression (ASE) in floral buds and leaf tissue of F1 offspring, indicative of cis-regulatory changes. We identified 1365 genes exhibiting ASE in floral buds and leaf tissue. These genes preferentially expressed alleles from outcrossing parents. Moreover, we found evidence that genes exhibiting ASE had a greater nonsynonymous diversity compared to synonymous diversity in the selfing parents. Our results suggest that the transition from outcrossing to high rates of self-fertilization may have the potential to shape the cis-regulatory genomic landscape of angiosperm species, but that the changes in ASE may be moderate, particularly during the early stages of this transition. PMID- 26990569 TI - The MRX Complex Ensures NHEJ Fidelity through Multiple Pathways Including Xrs2 FHA-Dependent Tel1 Activation. AB - Because DNA double-strand breaks (DSBs) are one of the most cytotoxic DNA lesions and often cause genomic instability, precise repair of DSBs is vital for the maintenance of genomic stability. Xrs2/Nbs1 is a multi-functional regulatory subunit of the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex, and its function is critical for the primary step of DSB repair, whether by homologous recombination (HR) or non-homologous end joining. In human NBS1, mutations result truncation of the N-terminus region, which contains a forkhead-associated (FHA) domain, cause Nijmegen breakage syndrome. Here we show that the Xrs2 FHA domain of budding yeast is required both to suppress the imprecise repair of DSBs and to promote the robust activation of Tel1 in the DNA damage response pathway. The role of the Xrs2 FHA domain in Tel1 activation was independent of the Tel1-binding activity of the Xrs2 C terminus, which mediates Tel1 recruitment to DSB ends. Both the Xrs2 FHA domain and Tel1 were required for the timely removal of the Ku complex from DSB ends, which correlates with a reduced frequency of imprecise end joining. Thus, the Xrs2 FHA domain and Tel1 kinase work in a coordinated manner to maintain DSB repair fidelity. PMID- 26990571 TI - MiR-301a regulates E-cadherin expression and is predictive of prostate cancer recurrence. AB - BACKGROUND: MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression post-transcriptionally. Dysregulation of miRNA has been implicated in the development and progression of prostate cancer. Through next generation miRNA sequencing, we recently identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. Of the five miRNAs, miR-301a had the strongest association with prostate cancer recurrence. Overexpression of miR-301a in prostate cancer cells, PC3, and LNCaP resulted in increased growth both in vitro and in xenografted tumors. We therefore sought to examine its role in prostate carcinogenesis in greater detail. METHODS: We examined the effect of miR 301a expression on biochemical recurrence and metastasis among 585 men treated with radical prostatectomy for prostate cancer. We examined the mechanism of growth deregulation by miR-301a in prostate cancer cells using analysis of the miRome of prostate cancer cell lines, quantitative PCR, and Western blotting. RESULTS: High levels of miR-301a (above the median) were associated with an increased risk of biochemical recurrence (adjusted hazard ratio [aHR] 1.42, 95% confidence interval (CI) 1.06-1.90, P = 0.002) but not of metastasis (aHR 0.84, 95%CI 0.41-1.70, P = 0.6) after adjustment for known prognostic factors. RNA transcriptome sequencing analysis of miR-301a overexpressing prostate cancer cell lines identified the tumor suppressor p63 as a potential direct miR-301a target. Transcriptome sequencing, qPCR and Western blotting showed that miR-301a induced epithelial-mesenchymal transition (EMT) in prostate cancer cells through a pathway initiated by p63 inhibition. Luciferase assay verified p63 as a direct target of miR-301a. Loss of p63 resulted in miR-205 downregulation, releasing Zeb1 and Zeb2 from inhibition, culminating in Zeb1/Zeb2 suppression of E cadherin. This pathway of growth alteration mediated by miR-301a upregulation was shown to be valid in prostate cancer cell lines and patient-derived tumors. CONCLUSIONS: These data indicate that miR-301a functions as an oncogene in prostate cancer by directly targeting the p63 tumor suppressor leading to loss of E-cadherin and EMT. Hence, miR-301a may serve as a novel biomarker in prostate cancer as well as a therapeutic target for prostate cancer management. Prostate 76:869-884, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990572 TI - Environmental layout complexity affects neural activity during navigation in humans. AB - Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation. PMID- 26990570 TI - Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes. AB - Interstitial fibrosis and tubular atrophy (IFTA) is found in approximately 25% of 1-year biopsies posttransplant. It is known that IFTA correlates with decreased graft survival when histological evidence of inflammation is present. Identifying the mechanistic etiology of IFTA is important to understanding why long-term graft survival has not changed as expected despite improved immunosuppression and dramatically reduced rates of clinical acute rejection (AR) (Services UDoHaH. http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expression profiles of 234 graft biopsy samples were obtained with matching clinical and outcome data. Eighty-one IFTA biopsies were divided into subphenotypes by degree of histological inflammation: IFTA with AR, IFTA with inflammation, and IFTA without inflammation. Samples with AR (n = 54) and normally functioning transplants (TX; n = 99) were used in comparisons. A novel analysis using gene coexpression networks revealed that all IFTA phenotypes were strongly enriched for dysregulated gene pathways and these were shared with the biopsy profiles of AR, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. These molecular biopsy profiles correlated with future graft loss in IFTA samples without inflammation. PMID- 26990573 TI - Biologic Therapeutic Drug Monitoring in Australia. PMID- 26990575 TI - TIA Due to Cerebral Fat Embolism Following Lipid-Based Sonographic Contrast Agent Injection. PMID- 26990574 TI - Integrated landscape approaches to managing social and environmental issues in the tropics: learning from the past to guide the future. AB - Poverty, food insecurity, climate change and biodiversity loss continue to persist as the primary environmental and social challenges faced by the global community. As such, there is a growing acknowledgement that conventional sectorial approaches to addressing often inter-connected social, environmental, economic and political challenges are proving insufficient. An alternative is to focus on integrated solutions at landscape scales or 'landscape approaches'. The appeal of landscape approaches has resulted in the production of a significant body of literature in recent decades, yet confusion over terminology, application and utility persists. Focusing on the tropics, we systematically reviewed the literature to: (i) disentangle the historical development and theory behind the framework of the landscape approach and how it has progressed into its current iteration, (ii) establish lessons learned from previous land management strategies, (iii) determine the barriers that currently restrict implementation of the landscape approach and (iv) provide recommendations for how the landscape approach can contribute towards the fulfilment of the goals of international policy processes. This review suggests that, despite some barriers to implementation, a landscape approach has considerable potential to meet social and environmental objectives at local scales while aiding national commitments to addressing ongoing global challenges. PMID- 26990576 TI - Acteoside-mediates chemoprevention of experimental liver carcinogenesis through STAT-3 regulated oxidative stress and apoptosis. AB - In the absence of an effective therapy against Hepatocellular Carcinoma (HCC), chemoprevention remains an important strategy to circumvent morbidity and mortality. Here, we examined chemopreventive potential of Acteoside (ACT), a plant derived phenylethanoid glycoside against an environmental and dietary carcinogen, diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. ACT treatment (0.1 and 0.3% supplemented with diet) started 2 weeks before DEN challenge and continued for 18 weeks thereafter, showed a remarkable chemopreventive activity. ACT treatment resulted in reduced HCC nodules. Histopathology showed progressive tissue damage, necrosis (5 weeks), hepatocytic injury (10 weeks), anisonucleosis with presence of prominent nucleoli, sinusidal dilations, and lymphomono nuclear inflammation (18 weeks). Biochemical analysis showed hepatocytic injury (raised ALT, p < 0.001), inflammation [IL-6, IFN-gamma (p < 0.05), and TNF-alpha (p < 0.001)], apoptosis [elevated Caspase-3 (p < 0.001)]. ACT at 0.1 and 0.3% ameliorated DEN-induced pre-hepatocarcinogenic manifestations. Mechanistic studies of ACT chemoprevention was elucidated using Hep3B cells with an aim to develop an in vitro DEN-induced toxicity model. Hep3B was found to be a reliable and more sensitive towards DEN toxicity compared to HepG2 and HuH7 cells. ACT prevented DEN-induced cytotoxicity (p < 0.001), DNA damage, and genotoxicity (micronuclei test, DNA ladder test, Hoechst staining, cell cycle analysis). ACT significantly (p < 0.001) scavenged DEN-induced reactive oxygen species (ROS) levels and prevented mitochondrial membrane potential (MMP) loss. Immunoblotting showed ACT treatment reversed DEN-induced NF kappaB, Bax, Cytochrome C, Bcl-2, and Stat-3 levels. We conclude that chemoprotective effect of ACT is mediated by STAT-3 dependent regulation of oxidative stress and apoptosis and ACT has potential to be developed as a chemopreventive agent. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 782 798, 2016. PMID- 26990578 TI - Design, Synthesis, and Evaluation of Acrylamide Derivatives as Direct NLRP3 Inflammasome Inhibitors. AB - NLRP3 inflammasome plays a key role in the intracellular activation of caspase-1, processing of pro-inflammatory interleukin-1beta (IL-1beta), and pyroptotic cell death cascade. The overactivation of NLRP3 is implicated in the pathogenesis of autoinflammatory diseases, known as cryopyrin-associated periodic syndromes (CAPS), and in the progression of several diseases, such as atherosclerosis, type 2 diabetes, gout, and Alzheimer's disease. In this study, the synthesis of acrylamide derivatives and their pharmaco-toxicological evaluation as potential inhibitors of NLRP3-dependent events was undertaken. Five hits were identified and evaluated for their efficiency in inhibiting IL-1beta release from different macrophage subtypes, including CAPS mutant macrophages. The most attractive hits were tested for their ability to inhibit NLRP3 ATPase activity on human recombinant NLRP3. This screening allowed the identification of 14, 2-(2 chlorobenzyl)-N-(4-sulfamoylphenethyl)acrylamide, which was able to concentration dependently inhibit NLRP3 ATPase with an IC50 value of 74 MUm. The putative binding pose of 14 in the ATPase domain of NLRP3 was also proposed. PMID- 26990577 TI - Mechano-signalling pathways in an experimental intensive critical illness myopathy model. AB - KEY POINTS: Using an experimental rat intensive care unit (ICU) model, not limited by early mortality, we have previously shown that passive mechanical loading attenuates the loss of muscle mass and force-generation capacity associated with the ICU intervention. Mitochondrial dynamics have recently been shown to play a more important role in muscle atrophy than previously recognized. In this study we demonstrate that mitochondrial dynamics, as well as mitophagy, is affected by mechanosensing at the transcriptional level, and muscle changes induced by unloading are counteracted by passive mechanical loading. The recently discovered ubiquitin ligases Fbxo31 and SMART are induced by mechanical silencing, an induction that similarly is prevented by passive mechanical loading. ABSTRACT: The complete loss of mechanical stimuli of skeletal muscles, i.e. loss of external strain related to weight bearing and internal strain related to activation of contractile proteins, in mechanically ventilated, deeply sedated and/or pharmacologically paralysed intensive care unit (ICU) patients is an important factor triggering the critical illness myopathy (CIM). Using a unique experimental ICU rat model, mimicking basic ICU conditions, we have recently shown that mechanical silencing is a dominant factor triggering the preferential loss of myosin, muscle atrophy and decreased specific force in fast- and slow-twitch muscles and muscle fibres. The aim of this study is to gain improved understanding of the gene signature and molecular pathways regulating the process of mechanical activation of skeletal muscle that are affected by the ICU condition. We have focused on pathways controlling myofibrillar protein synthesis and degradation, mitochondrial homeostasis and apoptosis. We demonstrate that genes regulating mitochondrial dynamics, as well as mitophagy are induced by mechanical silencing and that these effects are counteracted by passive mechanical loading. In addition, the recently identified ubiquitin ligases Fbxo31 and SMART are induced by mechanical silencing, an induction that is reversed by passive mechanical loading. Thus, mechano-cell signalling events are identified which may play an important role for the improved clinical outcomes reported in response to the early mobilization and physical therapy in immobilized ICU patients. PMID- 26990579 TI - Medication management in comprehensive schools in Finland: teachers' perceptions. AB - OBJECTIVE: Many children who take medication require it during school time, and their participation in school activities could depend on it. The aim of this study was to identify whether schools have guidelines for medication management and to explore teachers' perceptions about medication administration practices and the characteristics affecting these practices using Bronfenbrenner's ecological systems theory as the framework. METHODS: A cross-sectional postal survey was conducted in Finland in 2010 covering a representative sample of comprehensive school teachers (n = 1700). The survey included sections on guidelines and practices for medication administration, beliefs about medicines, and background information on the respondent and the respondent's school. Quantitative and qualitative methods of analysis were used. KEY FINDINGS: The response rate was 56% (928/1664). At the national level (macrosystem), teachers reported uncertainty about existing laws and guidelines, while at the local level (exosystem), most of the teachers reported having medication management guidelines (73% primary; 76% lower secondary school). However, a majority described guidelines instructing them not to administer medicines to pupils. Medication management practices were found to differ depending on the province and size of school. At the personal level (microsystem), practices were also affected by teachers' experience of, and views about, medicines. CONCLUSION: No consistent medication administration guidelines exist in Finnish schools. Challenges were identified at all system levels of ecological theory. To ensure proper medication management, school staff need clear and consistent guidance developed in co-operation between different professions, and exploring ways to involve pharmacists in this task. PMID- 26990580 TI - Anxieties and coping methods of liver transplant recipients regarding pregnancy and delivery. AB - AIM: To clarify the anxieties experienced by liver transplant recipients and their methods of coping during pregnancy and delivery. BACKGROUND: The recent increase in liver transplantation among adults and the growth in the number of paediatric (until reproductive age) liver transplant recipients have caused an increase in the number of pregnancies and deliveries among patients who have undergone liver transplantation. DESIGN: A qualitative descriptive study. METHODS: Fourteen recipients experienced delivery after undergoing liver transplantation. Data were collected through semi-structured interviews from June 2012 - May 2013. The descriptions obtained about the anxieties felt during pregnancy and the methods for coping were analysed using qualitative content analysis. RESULTS: Regarding anxieties during pregnancy, the two core categories, that is, 'influences on the child born to the liver transplant recipient' and 'the liver transplant recipient's body', and seven other categories were extracted. As for methods of coping, seven categories were extracted such as consulting a healthcare professional, family member or a recipient with a similar experience; accepting the necessity of immunosuppressive therapy; staying positive and avoiding negative thoughts; and practising good health habits. CONCLUSIONS: Liver transplant recipients cope with anxieties about the effects of immunosuppressants on the child and worsening of their physical condition by consulting healthcare professionals and family members and by self-management to maintain their physical condition. Nurses should seek to understand the physical and psychosocial status of each recipient after liver transplantation and provide support to facilitate the physical and psychological stability of liver transplant recipients during pregnancy and delivery. PMID- 26990581 TI - Signaling via the NFkappaB system. AB - The nuclear factor kappa B (NFkappaB) family of transcription factors is a key regulator of immune development, immune responses, inflammation, and cancer. The NFkappaB signaling system (defined by the interactions between NFkappaB dimers, IkappaB regulators, and IKK complexes) is responsive to a number of stimuli, and upon ligand-receptor engagement, distinct cellular outcomes, appropriate to the specific signal received, are set into motion. After almost three decades of study, many signaling mechanisms are well understood, rendering them amenable to mathematical modeling, which can reveal deeper insights about the regulatory design principles. While other reviews have focused on upstream, receptor proximal signaling (Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 2004, 18:2195-2224; Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R. TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cell Mol Life Sci 2008, 65:2964-2978), and advances through computational modeling (Basak S, Behar M, Hoffmann A. Lessons from mathematically modeling the NF-kappaB pathway. Immunol Rev 2012, 246:221-238; Williams R, Timmis J, Qwarnstrom E. Computational models of the NF-KB signalling pathway. Computation 2014, 2:131), in this review we aim to summarize the current understanding of the NFkappaB signaling system itself, the molecular mechanisms, and systems properties that are key to its diverse biological functions, and we discuss remaining questions in the field. WIREs Syst Biol Med 2016, 8:227-241. doi: 10.1002/wsbm.1331 For further resources related to this article, please visit the WIREs website. PMID- 26990582 TI - Lessons from nature: signalling cascades associated with vertebrate brain anoxic survival. AB - NEW FINDINGS: What is the topic of this review? Although the mammalian brain is exquisitely sensitive to hypoxia, some turtles survive complete anoxia by decreasing metabolic demand to match reduced energy supply. These animal models may help to elucidate neuroprotective mechanisms and reveal novel therapeutic targets for diseases of oxygen deprivation. What advances does it highlight? The mitogen-activated protein kinases (MAPKs) are part of the suite of adaptive responses to anoxia that are modulated by adenosine, a 'retaliatory metabolite' released in early anoxia. In anoxic turtle neurons, upregulation of pro-survival Akt and extracellular signal-regulated kinase 1/2 and suppression of the p38MAPK and JNK pathways promote cell survival, as does the anoxic- and post-anoxic upregulation of the antioxidant methionine sulfoxide reductase. Mammalian neurons undergo rapid degeneration when oxygen supply is curtailed. Neuroprotective pathways are induced during hypoxia/ischaemia, but their analysis is complicated by concurrent pathological events. Survival mechanisms can be investigated in anoxia-tolerant freshwater turtle species, which survive oxygen deprivation and post-anoxic reoxygenation by entrance into a state of reversible hypometabolism. Many energy-demanding processes are suppressed, including ion flux and neurotransmitter release, whereas cellular protective mechanisms, including certain mitogen-activated protein kinases (MAPKs), are upregulated. This superfamily of serine/threonine kinases plays a significant role in vital cellular processes, including cell proliferation, differentiation, stress adaptation and apoptosis in response to external stimuli. Here, we report that neuronal survival relies on robust co-ordination between the major signalling cascades, with upregulation of the pro-survival Akt and extracellular signal regulated kinase 1/2 and suppression of the p38MAPK and JNK pathways. Other protective responses, including the upregulation of heat shock proteins and antioxidants, allow the turtle brain to abrogate potential oxidative stress upon reoxygenation. PMID- 26990583 TI - Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation. AB - Accumulating evidence has revealed three-dimensional (3D) culture could better mimic the stem cell niche in vivo in comparison with conventional two-dimensional (2D) culture. In this study, we found that bone marrow derived mesenchymal stem cells (BMSCs) cultured in 3D collagen scaffold (3D BMSCs) exhibited distinctive features including significantly enhancing neurotrophic factor secretions and reducing macrophage activations challenged by lipopolysaccharide (LPS) in vitro. To further evaluate 3D BMSCs' potential benefits to the regeneration of spinal cord injury (SCI), the 3D and 2D BMSCs were respectively implanted in rat hemisected SCI. Compared with 2D cohort, 3D BMSCs transplantation significantly reduced the expressions of inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 at 5 days after transplantation, markedly enhanced axonal regeneration, and promoted motor functional recovery during 8 weeks of observation. When Nocodazole was used to depolymerize the cytoskeleton of 3D BMSCs, the changed expressions of neurotrophic factors and inflammatory cytokines were blunted, at least partially. Thus synergistic effects of neuronal protection and immunomodulation of 3D BMSCs may lead to a better functional recovery of SCI and the underlying mechanism may involve the alteration of their cellular morphology because of 3D culture. This study contributes to a better understanding of the cellular characteristics of 3D BMSCs and provides a novel strategy to promote the repair of the injured spinal cord. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1759-1769, 2016. PMID- 26990584 TI - Outbreak of respiratory syncytial virus (RSV) infection in immunocompromised adults on a hematology ward. AB - We describe an outbreak of respiratory syncytial virus (RSV) infection on a hematology ward without allogeneic stem cell transplant patients. Twelve patients and one staff member infected with RSV were identified from the laboratory database. Five patients had lower respiratory tract infection, seven had upper respiratory tract infection, one was asymptomatic, and there were two (15.4%) deaths. Most patients had overlapping periods of potential infectiousness on the ward. Sequencing was possible on eight specimens and five of these had identical sequences. Results were consistent with transmission occurring both on the ward and by introduction of RSV from the community. J. Med. Virol. 88:1827-1831, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990585 TI - Tough love or bullying? New nurse transitional experiences. AB - AIMS AND OBJECTIVES: This qualitative paper reports on the transition experiences of new nurses and preceptors in Singapore, focussing on the construction of a supervisor strategy termed 'tough love'. The authors discuss the concept of tough love, as a metaphorical euphemism for workplace bullying and interrogate rationales from the data that behaviours associated with tough love, prepare nurses for independence and competence in their new responsibilities. BACKGROUND: Successful transition of new nurses to professional practice is dependent on the transition challenges they face at work. When new nurses are well supported in the clinical environment, retention occurs. However, when workplace adversity intensifies, nurse turnover rates increase. DESIGN: This qualitative study was conducted using a constructivist grounded theory approach. METHODS: New nurses (n = 26) and preceptors (n = 5) from five different hospitals participated in the study. Data were collected from semi-structured interviews and reflective journal entries and analysed using the constant comparative method. FINDINGS: Data analysis gave rise to the generation of a definition of tough love, not otherwise identified in the literature, as the negative behaviours of senior nurses towards new nurses, that is rationalised as a well-intentioned but nevertheless abusive strategy, used to condition targets into conforming to expected professional or organisational behaviour. CONCLUSIONS: The authors conclude that tough love behaviour damages the transition experience of new nurses and has the potential to influence decisions on whether to remain in a health organisation and indeed the profession. RELEVANCE TO CLINICAL PRACTICE: Given nursing shortages in Singapore and internationally and that the retention of new nurses appears to be part of the problem, tough love behaviours and cultures clearly need to be addressed if investment into training and recruitment are to be realised. PMID- 26990586 TI - Precepting at the time of a natural disaster. AB - BACKGROUND: Natural disasters strike communities that have varied degrees of preparedness, both physical and psychological. Rural communities may be particularly vulnerable as they often do not have the infrastructure or resources to prepare in advance. The psychological impact of a natural disaster is amplified in learners who may be temporary members of the community and therefore cannot draw on personal support during the crisis. They may turn to their clinical preceptors for guidance. CONTEXT: The Slave Lake fire (population 6782) in May 2011 and the High River flood (population 12 920) in June 2013 are examples of natural disasters that have occurred in rural Alberta, Canada. At the time of these critical incidents, three medical students and one family medicine resident from the two provincial medical schools were participating in rotations in these communities. INNOVATION: Although disasters occur rarely, there is a need for guidelines for preceptors from the learner perspective. Accordingly, using a modified Delphi approach, we captured the experiences of learners that were then refined into two themes, each containing three recommendations: considerations for action during a natural disaster and considerations for action after the acute crisis has passed. Although disasters occur rarely, there is a need for guidelines for preceptors from the learner perspective IMPLICATIONS: Our recommendations provide suggestions for practical solutions that build on the usual expectations of mentors and may benefit the student-teacher relationship at the time of a disaster and beyond. They are meant to initiate discussion regarding further study aimed towards creating recommendations for preceptor response that may cross disciplines. PMID- 26990587 TI - Erratum for Euro Surveill. 2014;19(17). PMID- 26990588 TI - Treatment of Patients with Nonradiographic Axial Spondyloarthritis Who Have Negative Magnetic Resonance Imaging Results and Normal C-Reactive Protein Levels at Baseline: Comment on the Article by Ward et al. PMID- 26990589 TI - The (6-4) Dimeric Lesion as a DNA Photosensitizer. AB - Based on our previous investigations into the photophysical properties of the 5 methyl-2-pyrimidone (Pyo) chromophore, we now extend our studies to the photobehavior of the dimeric (6-4) thymine photoproducts (6-4 PP) to evaluate their capability to act as instrinsic DNA photosensitizers. The lesion presents significant absorption in the UVB/UVA region, weak fluorescence emission, a singlet-excited-state energy of approximately 351 kJ mol(-1) , and a triplet excited-state energy of 297 kJ mol(-1) . Its triplet transient absorption has a maximum at 420-440 nm, a lifetime of around 7 MUs, and a high formation quantum yield, PhiISC =0.86. This species is efficiently quenched by thymidine. Its DNA photosensitizing properties are demonstrated by a series of experiments run on a pBR322 plasmid. The lesion photoinduces both single-strand breaks and the formation of cyclobutane thymine dimers. Altogether, these results show that, the substitution of the pyrimidone ring at C4 by a 5-hydroxy-5,6-dihydrothymine does not cancel out the photosensitization properties of the chromophore. PMID- 26990590 TI - Pathophysiology of recurrent hepatocellular carcinoma after radiofrequency ablation. AB - Radiofrequency ablation (RFA) is effective for the local control of hepatocellular carcinoma (HCC), particularly when a patient's liver functional reserve does not allow radical resection. There is controversy regarding the superiority of surgical resection compared with RFA for such patients, particularly those with three or fewer tumors with diameters <=3 cm. Moreover, HCC often recurs after RFA, and the tumor cells show distinct phenotypic changes. Incomplete ablation accounts for tumor recurrence, and recent studies provide new insights into the biological mechanisms responsible for the pathological changes of HCC after RFA. This review focuses on the roles of epithelial-mesenchymal transition and cancer stemness that are driven by a mechanism that involves microRNA-mediated upregulation of hypoxia-inducible factor-1. The studies reviewed here provide compelling evidence that complete ablation of HCC is required to prevent recurrence and indicate that further research is urgently required to develop a new systematic strategy to prevent tumor recurrence by targeting hypoxia-inducible factor-1. PMID- 26990591 TI - Effect of Potassium on the Mechanisms of Biomass Pyrolysis Studied using Complementary Analytical Techniques. AB - Complementary analytical methods have been used to study the effect of potassium on the pyrolysis mechanisms of cellulose and lignocellulosic biomasses. Thermogravimetry, calorimetry, high-temperature (1) H NMR spectroscopy (in situ and real-time analysis of the fluid phase formed during pyrolysis), and water extraction of quenched char followed by size-exclusion chromatography coupled with mass spectrometry have been combined. Potassium impregnated in cellulose suppresses the formation of anhydrosugars, reduces the formation of mobile protons, and gives rise to a mainly exothermic signal. The evolution of mobile protons formed from K-impregnated cellulose has a very similar pattern to the evolution of the mass loss rate. This methodology has been also applied to analyze miscanthus, demineralized miscanthus, miscanthus re-impregnated with potassium after demineralization, raw oak, and Douglas fir. Hydrogen mobility and transfer are of high importance in the mechanisms of biomass pyrolysis. PMID- 26990593 TI - Determination of fluoroquinolones in environmental water and milk samples treated with stir cake sorptive extraction based on a boron-rich monolith. AB - In this study, a new stir cake sorptive extraction using a boron-rich monolith as the adsorbent was prepared by the in situ copolymerization of vinylboronic anhydride pyridine complex and divinylbenzene. The effect of preparation parameters, including the ratio of vinylboronic anhydride pyridine complex and divinylbenzene, monomer mixture, and porogen solvent, on extraction performance was investigated thoroughly. The physicochemical properties of the adsorbent were characterized by infrared spectroscopy, scanning electron microscopy, and mercury intrusion porosimetry. Several conditions affecting the extraction efficiency were investigated in detail. Under the optimized conditions, a convenient and sensitive method for the determination of trace fluoroquinolones residues in water and milk samples was established by coupling stir cake sorptive extraction with high-performance liquid chromatography and diode array detection. The limits of detection for the target compounds were 0.10-0.26 and 0.11-0.22 MUg/L for water and milk samples, respectively. In addition, the developed method showed good linearity, repeatability, and precision. Finally, the proposed method was successfully applied for the detection of trace fluoroquinolones residues in environmental water and milk samples. Satisfactory recoveries were obtained for the determination of fluoroquinolones in spiking samples that ranged from 68.8 to 120%, with relative standard deviations below 10% in all cases. PMID- 26990592 TI - Recombinant horseradish peroxidase variants for targeted cancer treatment. AB - Cancer is a major cause of death. Common chemo- and radiation-therapies damage healthy tissue and cause painful side effects. The enzyme horseradish peroxidase (HRP) has been shown to activate the plant hormone indole-3-acetic acid (IAA) to a powerful anticancer agent in in vitro studies, but gene directed enzyme prodrug therapy (GDEPT) studies showed ambivalent results. Thus, HRP/IAA in antibody directed enzyme prodrug therapy (ADEPT) was investigated as an alternative. However, this approach has not been intensively studied, since the enzyme preparation from plant describes an undefined mixture of isoenzymes with a heterogenic glycosylation pattern incompatible with the human system. Here, we describe the recombinant production of the two HRP isoenzymes C1A and A2A in a Pichia pastoris benchmark strain and a glyco-engineered strain with a knockout of the alpha-1,6-mannosyltransferase (OCH1) responsible for hypermannosylation. We biochemically characterized the enzyme variants, tested them with IAA and applied them on cancer cells. In the absence of H2 O2 , HRP C1A turned out to be highly active with IAA, independent of its surface glycosylation. Subsequent in vitro cytotoxicity studies with human T24 bladder carcinoma and MDA-MB-231 breast carcinoma cells underlined the applicability of recombinant HRP C1A with reduced surface glycoslyation for targeted cancer treatment. Summarizing, this is the first study describing the successful use of recombinantly produced HRP for targeted cancer treatment. Our findings might pave the way for an increased use of the powerful isoenzyme HRP C1A in cancer research in the future. PMID- 26990594 TI - Atomic-Scale Determination of Active Facets on the MoVTeNb Oxide M1 Phase and Their Intrinsic Catalytic Activity for Ethane Oxidative Dehydrogenation. AB - Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) has been used to image the basal {001} plane of the catalytically relevant M1 phase in MoVTeNb complex oxides. Facets {010}, {120}, and {210} are identified as the most frequent lateral termination planes of the crystals. Combination of STEM with He ion microscopy (HIM) images, Rietveld analysis, and kinetic tests reveals that the activation of ethane is correlated to the availability of facets {001}, {120}, and {210} at the surface of M1 crystals. The lateral facets {120} and {210} expose crystalline positions related to the typical active centers described for propane oxidation. Conversely, the low activity of the facet {010} is attributed to its configuration, consisting of only stable M6 O21 units connected by a single octahedron. Thus, we quantitatively demonstrated that differences in catalytic activity among M1 samples of equal chemical composition depend primarily on the morphology of the particles, which determines the predominant terminating facets. PMID- 26990596 TI - Langerhans cell collections, but not eosinophils, are clues to a diagnosis of allergic contact dermatitis in appropriate skin biopsies. AB - BACKGROUND: Langerhans cell collections (LCCs) and eosinophils are traditionally considered histologic clues to allergic contact dermatitis (ACD), but rigorous histologic analyses are limited. We correlated the presence of LCCs and eosinophils in skin biopsies with patch test results in patients evaluated for ACD. METHODS: Charts of all patients patch tested and biopsied at one institution from 2011 to 2013 were reviewed. Biopsies had to have a diagnosis of either spongiotic dermatitis, psoriasiform dermatitis or mixed psoriasiform/spongiotic dermatitis. Various histologic parameters were assessed, including the presence of LCCs and number of eosinophils. DESIGN: A total of 68 biopsies met study criteria. Of these, 27 (40%) had >=1 LCC. Twenty-one out of 27 (78%) with >=1 LCC were patch test positive; 6 were patch test negative (22%). Of 41 cases with no LCCs, 23 were patch test positive (23/41, 56%) and 18 were patch test negative (18/41, 44%). LCCs were significantly more common in patch test positive patients (p = 0.046). Eosinophil count did not significantly differ in patch test positive and negative cases (p = 0.216). CONCLUSION: LCCs are significantly more common in patch test positive cases. There were no differences with regards to presence of eosinophils between patch test positive and negative groups. PMID- 26990597 TI - Ionic Compatibilization of Cellulose Nanocrystals with Quaternary Ammonium Salt and Their Melt Extrusion with Polypropylene. AB - On account to their high mechanical properties along with high reinforcing capacity, cellulose nanocrystals (CNCs) could be the ultimate choice for polymer nanocomposites as filler. Recently, different strategies have been investigated for the melt extrusion of CNC-based polymer nanocomposites because it is a solvent-free process and because this technique is more viable for commercial industrialization. However, most thermoplastic polymers are processed at high temperatures, and sulfuric acid preparation of CNC limits the processing because of surface sulfate groups degradation. In this study we profitably used these negatively charged groups, and quaternary ammonium salt was ionically adsorbed on CNC by a simple aqueous method. Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction were used to characterize adsorbed CNC, and changes in polarity were investigated by contact angle measurements. Modified CNC was extruded with polypropylene at 190 degrees C, and the ensuing composites were characterized in terms of mechanical (by dynamic mechanical analysis and tensile tests), thermal (by differential scanning calorimetry), and morphological (scanning electron microscopy) properties. The melt rheology of PP-based nanocomposites was also reported. PMID- 26990595 TI - Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction. AB - AIMS: Concomitant renin-angiotensin-aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF. METHODS: This was an open-label, noncontrolled single-sequence study. After a 24-h run-in period, patients (n = 30) with HFrEF (EF <= 40%; NYHA class II-IV) received LCZ696 100 mg twice daily (bid) for 7 days and 200 mg bid for 14 days, along with standard treatment for heart failure (HF) (except angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]). RESULTS: On Day 21, significant increases were observed in the plasma biomarkers indicative of neprilysin and RAAS inhibition (ratio-to-baseline: cyclic guanosine monophosphate [cGMP], 1.38; renin concentration and activity, 3.50 and 2.27, respectively; all, P < 0.05). Plasma NT-proBNP levels significantly decreased at all the time points on Days 7 and 21; plasma aldosterone and endothelin-1 levels significantly decreased on Day 21 (all, P < 0.05). Following administration of LCZ696, the Cmax of sacubitril (neprilysin inhibitor prodrug), LBQ657 (active neprilysin inhibitor), and valsartan were reached within 0.5, 2.5, and 2 h. Between 100- and 200-mg doses, the Cmax and AUC0-12 h for sacubitril and LBQ657 were approximately dose-proportional while that of valsartan was less than dose-proportional. CONCLUSIONS: Treatment with LCZ696 for 21 days was well tolerated and resulted in plasma biomarker changes indicative of neprilysin and RAAS inhibition in patients with HF. The pharmacokinetic exposure of the LCZ696 analytes in patients with HF observed in this study is comparable to that observed in the pivotal Phase III study. PMID- 26990599 TI - Repair of congenital diaphragmatic hernia during extracorporeal life support: experience with six neonates. AB - BACKGROUND: The management of congenital diaphragmatic hernia (CDH) in neonates has evolved considerably over the last three decades. Initial stabilization followed by surgical repair is the current standard of care. A subset fails to achieve adequate oxygenation with medical management, including the use of high frequency oscillation and inhaled nitric oxide. The mortality in this group exceeds 80% without additional management strategies. Extracorporeal life support (ECLS) is a well-established modality for managing these neonates with CDH and has been shown to improve early survival in selected cases. METHODS: This is a retrospective analysis of six neonates with CDH who underwent repair during ECLS between September 2011 and November 2014. RESULTS: Of 24 admissions with CDH, there were six neonates (25%) who required ECLS. All the six had CDH repair during ECLS. There were no intra-operative bleeding complications. There were no clotting complications related to stopping heparin during CDH repair. There was one hospital death. Five neonates were weaned from ECLS and discharged home. CONCLUSIONS: Data from our small cohort of patients illustrate that early survival is possible in extremely compromised neonates who otherwise would have died without ECLS. Our experience demonstrates that CDH repair can safely be performed during ECLS. Use of ECLS, early repair during ECLS, lung protective ventilation strategies and aggressive management of pulmonary hypertension were associated with good early survival. ECLS should be considered as an integral part of therapeutic armamentarium for CDH in neonates. PMID- 26990598 TI - An economic evaluation of contingency management for completion of hepatitis B vaccination in those on treatment for opiate dependence. AB - AIMS: To determine whether the provision of contingency management using financial incentives to improve hepatitis B vaccine completion in people who inject drugs entering community treatment represents a cost-effective use of health-care resources. DESIGN: A probabilistic cost-effectiveness analysis was conducted, using a decision-tree to estimate the short-term clinical and health care cost impact of the vaccination strategies, followed by a Markov process to evaluate the long-term clinical consequences and costs associated with hepatitis B infection. SETTINGS AND PARTICIPANTS: Data on attendance to vaccination from a UK cluster randomized trial. INTERVENTION: Two contingency management options were examined in the trial: fixed versus escalating schedule financial incentives. MEASUREMENT: Life-time health-care costs and quality-adjusted life years discounted at 3.5% annually; incremental cost-effectiveness ratios. FINDINGS: The resulting estimate for the incremental life-time health-care cost of the contingency management strategy versus usual care was L21.86 [95% confidence interval (CI) = -L12.20 to 39.86] per person offered the incentive. For 1000 people offered the incentive, the incremental reduction in numbers of hepatitis B infections avoided over their lifetime was estimated at 19 (95% CI = 8-30). The probabilistic incremental cost per quality adjusted life-year gained of the contingency management programme was estimated to be L6738 (95% CI = L6297 7172), with an 89% probability of being considered cost-effective at a threshold of L20 000 per quality-adjusted life years gained (97.60% at L30 000). CONCLUSIONS: Using financial incentives to increase hepatitis B vaccination completion in people who inject drugs could be a cost-effective use of health care resources in the UK as long as the incidence remains above 1.2%. PMID- 26990600 TI - A Drug-Free Tumor Therapy Strategy: Cancer-Cell-Targeting Calcification. AB - Herein, we propose a drug-free approach to cancer therapy that involves cancer cell targeting calcification (CCTC). Several types of cancer cells, such as HeLa cells, characterized by folate receptor (FR) overexpression, can selectively adsorb folate (FA) molecules and then concentrate Ca(2+) locally to induce specific cell calcification. The resultant calcium mineral encapsulates the cancer cells, inducing their death, and in vivo assessments confirm that CCTC treatment can efficiently inhibit tumor growth and metastasis without damaging normal cells compared with conventional chemotherapy. Accordingly, CCTC remarkably improve the survival rate of tumor mice. Notably, both FA and calcium ions are essential ingredients in human metabolism, which means that CCTC is a successful drug-free method for tumor therapy. This achievement may further represent an alternative cancer therapy characterized by selective calcification based substitution of sclerosis for tumor disease. PMID- 26990601 TI - Real time kinetic flow cytometry measurements of cellular parameter changes evoked by nanosecond pulsed electric field. AB - Nanosecond pulsed electric field (nsPEF) is a novel method to increase cell proliferation rate. The phenomenon is based on the microporation of cellular organelles and membranes. However, we have limited information on the effects of nsPEF on cell physiology. Several studies have attempted to describe the effects of this process, however no real time measurements have been conducted to date. In this study we designed a model system which allows the measurement of cellular processes before, during and after nsPEF treatment in real time. The system employs a Vabrema Mitoplicator(TM) nsPEF field generating instrument connected to a BD Accuri C6 cytometer with a silicon tube led through a peristaltic pump. This model system was applied to observe the effects of nsPEF in mammalian C6 glioblastoma (C6 glioma) and HEK-293 cell lines. Viability (using DRAQ7 dye), intracellular calcium levels (using Fluo-4 dye) and scatter characteristics were measured in a kinetic manner. Data were analyzed using the FACSKin software. The viability and morphology of the investigated cells was not altered upon nsPEF treatment. The response of HEK-293 cells to ionomycin as positive control was significantly lower in the nsPEF treated samples compared to non-treated cells. This difference was not observed in C6 cells. FSC and SSC values were not altered significantly by the nsPEF treatment. Our results indicate that this model system is capable of reliably investigating the effects of nsPEF on cellular processes in real time. (c) 2016 International Society for Advancement of Cytometry. PMID- 26990602 TI - Adoption and success rates of perineal procedures for fistula-in-ano: a systematic review. AB - AIM: Several sphincter-preserving techniques have been described with extremely encouraging initial reports. However, more recent studies have failed to confirm the positive early results. We evaluate the adoption and success rates of advancement flap procedures (AFP), fibrin glue sealant (FGS), anal collagen plug (ACP) and ligation of intersphincteric fistula tract (LIFT) procedures based on their evolution in time for the management of anal fistula. METHOD: A PubMed search from 1992 to 2015. An assessment of adoption, duration of study and success rate was undertaken. RESULTS: We found 133 studies (5604 patients): AFP (40 studies, 2333 patients), FGS (31 studies, 871 patients), LIFT (19 studies, 759 patients), ACP (43 studies, 1641 patients). Success rates ranged from 0% to 100%. Study duration was significantly associated with success rates in AFP (P = 0.01) and FGS (P = 0.02) but not in LIFT or ACP. The duration of use of individual procedures since first publication was associated with success rate only in AFP (P = 0.027). There were no statistically significant differences in success rates relative to the number of the patients included in each study. CONCLUSION: Success and adoption rates tend to decrease with time. Differences in patient selection, duration of follow-up, length of availability of the individual procedure and heterogeneity of treatment protocols contribute to the diverse results in the literature. Differences in success rates over time were evident, suggesting that both international trials and global best practice consensus are desirable. Further prospective randomized controlled trials with homogeneity and clear objective parameters would be needed to substantiate these findings. PMID- 26990604 TI - A Silicon-Based Nanothin Film Solid Oxide Fuel Cell Array with Edge Reinforced Support for Enhanced Thermal Mechanical Stability. AB - A silicon-based micro-solid oxide fuel cell (MU-SOFC) with electrolyte membrane array embedded in a thin silicon supporting membrane, featuring a unique edge reinforcement structure, was demonstrated by utilizing simple silicon micromachining processes. The square silicon supporting membrane, fabricated by combining deep reactive ion etching and through-wafer wet etching processes, has thicker edges and corners than the center portion of the membrane, which effectively improved the mechanical stability of the entire fuel cell array during cell fabrication and cell operation. The 20 MUm thick single crystalline silicon membrane supports a large number of 80 nm thick free-standing yttria stabilized zirconia (YSZ) electrolytes. The fuel cell array was stably maintained at the open circuit voltage (OCV) of 1.04 V for more than 30 h of operation at 350 degrees C. A high peak power density of 317 mW/cm(2) was obtained at 400 degrees C. During a rigorous in situ thermal cycling between 150 and 400 degrees C at a fast cooling and heating rate of 25 degrees C/min, the OCV of the MU-SOFC recovered to its high value of 1.07 V without any drop caused by membrane failure, which justifies the superior thermal stability of this novel cell architecture. PMID- 26990603 TI - Effects of chemical additives on the fermentation quality and N distribution of alfalfa silage in south of China. AB - In order to better utilize the last cut alfalfa harvested before killing frost in a high moisture environment, the effects of chemical additives on the quality of alfalfa silage were studied in south of China. The alfalfa was freshly harvested at branching stage, and wilted by dry matter content of about 300 g/kg (fresh matter basis). Silage was prepared by using a small-scale silage fermentation system, where sucrose, potassium citrate, sodium carbonate, formic acid, acetic acid and propionic acid were used as silage additives, and no additives served as control. These silos were stored at ambient temperature (5-20 degrees C), and the silage qualities were analyzed after 120 days of fermentation. All additive treatments affected the chemical composition and N distribution, increased the water-soluble content and crude protein contents, decreased non-protein nitrogen (NPN) content, and enhanced the in vitro ruminal dry matter digestibility (except for sodium carbonate). Silages treated with organic acids were preserved with significantly (P < 0.05) lower pH value, ethanol content and NPN content compared with control. When the fermentation quality, chemical composition and N distribution were considered, the treatment with sucrose or organic acids resulted in high quality of alfalfa silage ensiled before killing frost, with formic acid having the best effect. PMID- 26990606 TI - Aluminum Oxide Sandblasting of Hexagonal Coping and Abutment: Influence on Retention and Marginal Leakage Using Temporary Cements. AB - PURPOSE: To compare the tensile strength and marginal leakage of prefabricated abutments/copings, with or without surface sandblasting with aluminum oxide, luted with a calcium hydroxide-based temporary cement (CH, Dycal; Dentsply, Petropolis, RJ, Brazil) or a noneugenol zinc oxide cement (ZO, Temp Bond NE; Kerr, Orange, CA). MATERIALS AND METHODS: A total of 48 CeraOne abutment analogs and respective copings were divided into 6 groups (n = 8) according to the component that was sandblasted: the coping only, coping + abutment or no sandblasting and the temporary cement used: CH or ZO. After cementation, the samples underwent 500 thermal cycles (5 degrees C +/- 2 degrees C and 55 degrees C +/- 2 degrees C) and were subsequently immersed in an aqueous solution of 0.5% basic fuchsine dye for 24 hours. Next, the tensile test was performed, and microleakage was assessed qualitatively. Data were analyzed using Mann-Whitney, Kruskal-Wallis tests, followed by the Student-Newman-Keuls test (alpha = 0.05). RESULTS: CH cement showed a tensile strength (245.6 N) significantly higher than that of the ZO (18.1 N). Sandblasting both abutment and coping increased tensile strength by 1.7 times. Marginal leakage was not influenced by sandblasting; however, CH presented less microleakage. CONCLUSION: Aluminum oxide sandblasting of the coping and abutment favored the tensile strength of temporary cements and the CH showed a higher tensile strength and less microleakage than did the ZO cement. PMID- 26990605 TI - The role of socio-economic and clinical factors on HbA1c in children and adolescents with type 1 diabetes: an Italian multicentre survey. AB - OBJECTIVE: To identify the role of the family's socio-economic and clinical characteristics on metabolic control in children and adolescents with type 1 diabetes. METHODS: In this cross-sectional, multicentre study, 768 subjects with type 1 diabetes under 18 years of age were consecutively recruited from January 2008 to February 2009. Target condition was considered for HbA1c values <7.5% (<58 mmol/mol). A multiple correspondence analysis (MCA) was performed to analyze the association between the socio-economic and clinical characteristics of the participants. A logistic regression analysis was performed to identify factors associated with the subjects metabolic control. In both analyses, the family's socio-economic status was represented, measured by the Hollingshead Four-Factor Index of Social Status (SES) or by parental years of education. RESULTS: A total of 28.1% of subjects reached target HbA1c values. The MCA identified a strong association between at-target condition and several factors: high levels of SES or high levels of parental education, the use of the carbohydrate counting system, the use of insulin pumps, the use of the insulin delivery system over a short period of time, a normal body mass index. The logistic regression analysis showed that SES and the mother's years of education were significantly associated with the target condition [odds ratio (OR): 1.01, 95% confidence interval (CI): 1.01-1.03, p = 0.029; OR: 1.05, 95% CI: 1.01-1.10, p = 0.027, respectively). CONCLUSIONS: Personal, clinical, and family characteristics were found to be associated with HbA1c target. Their identification can be crucial in addressing strategies to optimize metabolic control and improve diabetes management. PMID- 26990607 TI - Newly acquired kiwi fruit allergy after bone marrow transplantation from a kiwi allergic donor. AB - BACKGROUND: The phenomenon of allergy transfer from an allergic donor to a non allergic recipient via hematopoietic cell transplantation has been described by several reports. However, it could not yet been conclusively shown that allergic reaction of the recipient is elicited by the donor's cells. OBJECTIVES: In the case of a 46-year-old male patient who - for the first time in his life - had two episodes of oral allergic syndrome upon kiwi consumption after having received myeloablative hematopoietic stem cell transplantation (HCT) from his kiwi allergic sister, we aimed to clarify the origin of allergen reactive cells in the donor. We not only intended to demonstrate if allergy was transferred by HCT but also to present an experimental workup for the analysis of allergy transfer by HCT. METHODS: Allergic sensitization to kiwi in recipient and donor was proven by ImmunoCAP. Furthermore, origin of peripheral blood mononuclear cells (PBMCs) was analyzed by chromosomal fluorescence in situ hybridization (FISH). To confirm allergic reaction and activation of hematopoietic cells by customized kiwi extract, we performed basophil activation test from whole blood as well as T cell proliferation assays from purified PBMCs of both recipient and donor. RESULTS: Basophil activation upon kiwi extract was demonstrated in both recipient and donor. Besides, we showed proliferation of CD4(+) T cells after incubation with kiwi extract. FISH analysis proved that hematopoietic cells of the male recipient completely originated from the female donor. CONCLUSION: Exemplified in this patient, we show for the first time that allergy transfer is mediated by the donor's cells. Moreover, our experimental approach using customized kiwi extract to prove contribution of kiwi-specific T and B cells in both kiwi-allergic recipient and donor could serve as a model approach for future studies. PMID- 26990608 TI - [Storytelling in Health Journalism: Online Survey of Health Journalists on Definition and Use]. AB - Background: Although health information is of great interest and plays an important role in almost all media, there are very few studies on the actual work of health journalists. Methods: A quantitative online survey with qualitative elements on the definition and use of storytelling in health journalism was carried out among members of various professional journalists' associations (n=86). Results: The results suggest that health journalists understand storytelling especially as a term used when an article has a dramatic construction, and the story is about real people. As reasons for using storytelling, health journalists primarily name the understandable and clear presentation of medical issues. They see better chances for identification and establishing a relationship to the readers' lives. Of particular importance seems to be that narrative elements do not distort the facts and protect the privacy rights of persons mentioned in case reports. PMID- 26990609 TI - [Prevalence of Gastroschisis, Omphalocele, Spina Bifida and Orofacial Clefts of Neonates from January 2000 to December 2010 in Leipzig, Saxony, Saxony-Anhalt and Germany]. AB - BACKGROUND: Malformations are the most common cause of death in infancy. Numerous studies indicate an increased prevalence of malformations in neonates in recent years in some countries around the world. This study analyzed local and national trends of the prevalences of gastroschisis, omphalocele, spina bifida and orofacial clefts during 2000 till 2010 in Leipzig, Saxony, Saxony-Anhalt and Germany. METHODS: The prevalence of neonatal malformations was studied retrospectively from January 2000 till December 2010 using 4 sources from Leipzig, Saxony, Saxony-Anhalt and Germany. RESULTS: Between 2000 and 2010, the prevalence in Germany and in Saxony, respectively was 1.97/2.12 (gastroschisis), 1.63/1.48 (omphalocele), 5.80/8.11 (orofacial clefts) and 2.92/2.50 (spina bifida) of 10 000 live births. In Saxony, a small increase in prevalence was detected (OR/year: 1.01-1.09). In Germany, the prevalence of malformations also increased significantly (OR/year: 1.01-1.04) with the exception of the prevalence of spina bifida which seemed to decline (OR/year 0.986 (0.97-1.0), p adjust=0.04). CONCLUSION: Whether or not there has been an actual increase in the prevalence of neonatal malformations in Germany over the years or the apparent increase is just due to bias, coding errors, multiple reporting and/or false registration and codification remains unclear. Importantly, in Germany, since prevalence of malformations is monitored prospectively only in Saxony-Anhalt and Rhineland-Palatinate, only in these states is it possible to recognize recent changes. For early identification of changes in prevalence and timely implementation of preventive measures, a nationwide register or additional regional registers are deemed necessary. PMID- 26990610 TI - [Sex/Gender-sensitive Research - A Survey of Epidemiologists in Germany]. AB - BACKGROUND AND AIMS: Epidemiology is the basic science of Public Health and has to provide high-quality scientific evidence for disease prevention and health care. Sex/Gender, as social and biological structure categories of population, play a central role in the analysis of epidemiological data. Whether and how epidemiologists incorporate sex/gender aspects in their research, their attitudes, needs and requirements they have in this context have hardly been investigated. These questions were addressed in a survey of epidemiologists in Germany. METHODS: With the support of the respective scientific societies, an online survey was conducted of German epidemiologists, and the data subjected to descriptive analysis. RESULTS: Approximately 64% of the 276 participants (response rate 25%) were female and 75% worked in the academic field. 70% reported having had experience in sex/gender-sensitive research and 83% expressed future interest in this topic. Issues mentioned as important were interaction of gender aspects and other factors of social inequality as well as the inclusion of sex and gender in all phases of the research process. Women and younger participants reported more experience and more needs concerning sex/gender sensitive research. To facilitate further incorporation of sex/gender-sensitive research in epidemiology, special workshops/tutorials at the respective scientific societies' annual meetings and online information materials were rated as important. CONCLUSION: Due to the low response rate, a positive selection of participants cannot be ruled out. The results show that, while a large group of epidemiologists had experience and interest in gender-sensitive research, there are some with less interest. Possible starting points for the strengthening of sex/gender-sensitivity research include further training and involvement of scientific societies in the process. PMID- 26990611 TI - [Optimization of Community Health Care: First Experiences of the Office for Medical Care in Districts and Municipalities of Bavaria]. AB - Background: Demographic changes pose serious challenges for the healthcare system. One important goal is to sustain the local healthcare provision in the future - especially in rural areas. In this context, more attention must be given to the statutory health service by communal as well as state authorities. Most of the municipalities have to tackle this problem for the first time and, due to lack of support, are faced with serious impediments. The aim of this paper is to describe the sphere of action of the Office for Medical Care in Districts and Municipalities (OMCDM) as well as its core outcome. Methods: The Bavarian Ministry of Health and Care (StMGP) established the OMCDM at the Bavarian Health and Food Safety Authority to support communal authorities. On behalf of the StMGP, this office analyses the existing set-ups of local health services and advises local authorities on improvement. For 2012-2015, the OMCDM database was analyzed for frequency and main reasons of contact with health services. Results: The action of the OMCDM is driven by a comprehensive assessment, specialist counseling, and networking to develop action potential for the individual local health authorities. Over the past four years, there has been an increasing demand for support. Until 2015-11-30, 233 cases of counseling and 155 intensive counseling cases were recorded. The topics most frequently mentioned in these consultations were primary care by General Practitioners (68%) and specialist care (29%). Other important issues were the search for successors (33%), the establishment of new practices (23%) and opening of branch practices (18%). Conclusion: On behalf of Bavarian government, the OMCDM offers easy access to objective and neutral counseling about statutory health services for Bavarian municipalities. This offer has been used frequently by districts and municipalities. Primary care by general practitioners on the local level was the most common reason to contact the OMCDM. The establishment of the Office for Medical Care in Districts and Municipality is a comprehensive support for local authorities and can be regarded as a pattern for other states in Germany. PMID- 26990612 TI - [The Role of Preferences in the German Long-Term Care Insurance - Results from Expert Interviews]. AB - BACKGROUND: As a result of population aging, the number of persons dependent on long-term care (LTC) is expected to increase considerably in Germany. Information about LTC preferences is important to decision-makers in future reforms. Taking into account the preferences of people can lead to a better congruence between desired and utilized LTC services. The aim of this study was to evaluate LTC preferences, their underlying reasons, and the potential to satisfy individual preferences within the German LTC insurance system. METHODS: Interviews with 20 LTC (insurance) experts in Germany between July and September 2014 were analyzed using qualitative content analysis methods. RESULTS: Irrespective of the care setting, people prefer flexible LTC (services), which allow for as much autonomy and independence as possible. Ideally, care is provided by close relatives at the dependent's home. Besides informal homecare, professional care at home is also (becoming increasingly) important, whereas inpatient LTC (nursing home) is rarely preferred over homecare arrangements. To most LTC dependents, interpersonal needs are more important than bodily and professional aspects of care. CONCLUSION: While the flexible choices and manifold options to combine services (high degree of person-centeredness) within the German LTC insurance constitute an important basis for the satisfaction of individual preferences, the widespread lack of information about entitlements, costs of services, and corresponding LTC options in the general population (future dependents) substantially hampers long-term care that is in line with preferences. PMID- 26990613 TI - [Does the Prevention Act Improve Prevention in Pediatric Outpatient Settings!?] AB - Aim of the study: The Prevention Act was adopted by the German Federal Parliament on 18.06.2015. The paediatric practice is an important place from which to reach out to children and teenagers and to positively influence them through targeted prevention services in their health-related behaviour. It is therefore an important setting for the implementation of the Prevention Act. Could the delegation of prevention services to qualified medical assistants promote the successful implementation of the Prevention Act? Since 2003, medical assistants have qualified as "Prevention Assistants" after completing training courses and offered support in preventive services to children and teenagers in the paediatrician's office. The aim of this study was to improve the effectiveness of the training to increase the competence of the participants, expansion of preventive services for children and teenagers in the paediatrician's office and reduction of physician workload. Methodology: Training was accompanied by ongoing evaluation; there were two extensive studies in 2009 and 2011, respectively. Between 2003 and 2006 (n=126, after 75% response rate) and in 2011 (n=119 after 24% response rate), participants were assessed with standardized questionnaires, and in the survey of 2011, their employers also were interviewed, (n=76, after 22% response rate). Results: The prevention assistants assess their learning successes as good and are able to take over delegated tasks in the paediatrician's office. The involvement of a trained prevention assistant contributed to the transformation and re-establishment of prevention offers in paediatrician's offices and reduced physician workload. 44% of physicians felt that the time saved by prevention assistant was very good or good, 80% of physicians surveyed also indicated that prevention assistants carried out preventive consultations in the doctor's office. Conclusion: In light of the paediatricians' workload and their own wishes and demands, and for a targeted implementation of the Prevention Act, it is necessary to delegate preventive services to trained personnel. It is also possible to accomplish this task. It is necessary to introduce billing numbers in the fee schedule for doctors similar to the billing numbers for dental health prophylaxis. PMID- 26990614 TI - Surface electromyography analysis of blepharoptosis correction by transconjunctival incisions. AB - Upper eyelid movement depends on the antagonistic actions of orbicularis oculi muscle and levator aponeurosis. Blepharoptosis is an abnormal drooping of upper eyelid margin with the eye in primary position of gaze. Transconjunctival incisions for upper eyelid ptosis correction have been a well-developed technique. Conventional prognosis however depends on clinical observations and lacks of quantitatively analysis for the eyelid muscle controlling. This study examines the possibility of using the assessments of temporal correlation in surface electromyography (SEMG) as a quantitative description for the change of muscle controlling after operation. Eyelid SEMG was measured from patients with blepharoptosis preoperatively and postoperatively, as well as, for comparative study, from young and aged normal subjects. The data were analyzed using the detrended fluctuation analysis method. The results show that the temporal correlation of the SEMG signals can be characterized by two indices associated with the correlation properties in short and long time scales demarcated at 3ms, corresponding to the time scale of neural response. Aging causes degradation of the correlation properties at both time scales, and patient group likely possess more serious correlation degradation in long-time regime which was improved moderately by the ptosis corrections. We propose that the temporal correlation in SEMG signals may be regarded as an indicator for evaluating the performance of eyelid muscle controlling in postoperative recovery. PMID- 26990615 TI - Validity of the twitch interpolation technique for the assessment of quadriceps neuromuscular asymmetries. AB - This study examined the validity of the twitch interpolation technique for evaluating side-to-side asymmetries in quadriceps neuromuscular function. Fifty six subjects with a wide range of asymmetries (19 healthy, 24 with unilateral and 13 with bilateral anterior cruciate ligament reconstruction) took part in the study. Supramaximal electrical paired stimuli were delivered to the quadriceps muscle during and immediately after a maximal voluntary contraction (MVC) of the knee extensors (twitch interpolation technique). MVC torque, voluntary activation and resting doublet-evoked torque were measured separately for the two sides, and percent side-to-side asymmetries were calculated for each parameter. MVC torque asymmetry was plotted against voluntary activation asymmetry and doublet-evoked torque asymmetry, and a multiple regression analysis was also conducted. Significant positive correlations were observed between MVC torque asymmetry and both voluntary activation asymmetry (r=0.40; p=0.002) and doublet-evoked torque asymmetry (r=0.53; p<0.001), and their relative contribution to MVC torque asymmetry was comparable (r=0.64; p<0.001). These results establish the validity of the twitch interpolation technique for the assessment of neuromuscular asymmetries. This methodology could provide useful insights into the contribution of some neural and muscular mechanisms that underlie quadriceps strength deficits. PMID- 26990616 TI - Dimensions of medication adherence in African Americans with type 2 diabetes in rural North Carolina. AB - PURPOSE: Personal perceptions and beliefs are one of the least studied patient factors influencing medication adherence. This study explored adherence experiences of rural African Americans with type 2 diabetes in rural southeastern North Carolina. METHODS: Social-ecological theory guided a mixed methods approach. The Morisky Medication Adherence Scale (MMAS) assessed adherence. Clinical variables (HgA1c, fasting glucose levels, current medications) were obtained from medical records. Pearson correlation coefficients examined associations between demographics, clinical variables, and MMAS scores. Narrative data obtained from open-ended questions were analyzed through content analysis. RESULTS: The study enrolled 45 rural residents with longstanding type 2 diabetes (11 years, 31% on insulin). The majority of MMAS scores (63%) reflected low adherence (<6); 30% averaged moderate adherence (6 to <8). Males had poor metabolic control (HgA1c 9.0); female glycemic control was moderately good (7.2). Adherence was associated with having health insurance (r = .594, p = .001) and working for pay (r = .440, p = .05). Participants frequently underused medications without consulting a provider; financial limitations served as a major barrier. Perceptions that diabetes only occurs when "sugar is high" are inconsistent with the course of this chronic disease. CONCLUSIONS: High levels of nonadherence remain a major challenge for nursing care providers in economically distressed rural counties. PMID- 26990617 TI - Epidemic Dissemination of a Carbapenem-Resistant Acinetobacter baumannii Clone Carrying armA Two Years After Its First Isolation in an Italian Hospital. AB - This study describes the dissemination of a carbapenem-resistant Acinetobacter baumannii (CRAB) strain in a university hospital in Northeast Italy. Characterization of the outbreak strain was combined with a retrospective analysis of all CRAB isolates collected in the same hospital during the 5 years preceding the outbreak, with the aim of elucidating the origin of the epidemic spread. The outbreak strain was shown to belong to the International Clone II and carry the blaOXA-23 gene, flanked by two ISAba1 sequences in opposite orientation (Tn2006 arrangement). The epidemic clone harbored also the blaOXA-66 allele of the carbapenemase intrinsic to A. baumannii, the determinant of ArmA 16S rRNA methylase and a class 1 integron, with the aacA4, catB8, and aadA1 cassette array. Genotype analysis, performed by macrorestriction analysis and VRBA, revealed that isolates related to outbreak strain had been sporadically collected from inpatients in the 2 years preceding outbreak start. Carriage of blaOXA-66, armA, and the integron further supported relatedness of these isolates to the outbreak clone. Outbreak initially involved three medical wards, typically hosting elderly patients with a history of prolonged hospitalization. The study highlights the need to adopt strict infection control measures also when CRAB isolation appears to be a sporadic event. PMID- 26990619 TI - Genetic Association Between IL-21 Polymorphisms and Cryptorchidism in a Chinese Han Population. AB - AIMS: Increasing evidence suggests an association between interleukin gene polymorphisms and cryptorchidism. To investigate the relationship between IL-21 gene polymorphisms and cryptorchidism susceptibility, a comprehensive genetic association study in a Chinese Han population was conducted. METHODS AND RESULTS: A total of 328 men were enrolled in a case-control study (116 cases and 212 healthy controls). Three SNPs (rs907715, rs2055979, and rs12508721) of the IL-21 gene were genotyped using the TaqMan((r)) genotyping assay. For the rs2055979 C>A polymorphism, A allele carriers had significantly decreased cryptorchidism susceptibility (p = 0.021, odds ratios [OR] = 0.58, 95% confidence intervals [CI] = 0.37-0.93) in a dominant model (AA+CA vs. CC), a codominant model (AC vs. CC; p = 0.029, OR = 0.52, 95% CI = 0.31-0.85), and an overdominant model (AC vs. CC/AA; p = 0.0087, OR = 0.53, 95% CI = 0.33-0.86). However, no associations were identified for the rs907715 C>T and rs12508721 C>A polymorphisms. In the haplotype analyses, the C-C-T haplotype of rs907715-rs2055979-rs12508721 significantly increased the risk of cryptorchidism (p < 0.0001, OR = 5.251, 95% CI = 2.528-10.906). CONCLUSIONS: The rs2055979 C>A polymorphism of the IL-21 gene is associated with cryptorchidism susceptibility, and the C allele increases the risk of cryptorchidism in a Chinese Han population. PMID- 26990618 TI - 3D Super-Resolution Motion-Corrected MRI: Validation of Fetal Posterior Fossa Measurements. AB - PURPOSE: Current diagnosis of fetal posterior fossa anomalies by sonography and conventional MRI is limited by fetal position, motion, and by two-dimensional (2D), rather than three-dimensional (3D), representation. In this study, we aimed to validate the use of a novel magnetic resonance imaging (MRI) technique, 3D super-resolution motion-corrected MRI, to image the fetal posterior fossa. METHODS: From a database of pregnant women who received fetal MRIs at our institution, images of 49 normal fetal brains were reconstructed. Six measurements of the cerebellum, vermis, and pons were obtained for all cases on 2D conventional and 3D reconstructed MRI, and the agreement between the two methods was determined using concordance correlation coefficients. Concordance of axial and coronal measurements of the transcerebellar diameter was also assessed within each method. RESULTS: Between the two methods, the concordance of measurements was high for all six structures (P < .001), and was highest for larger structures such as the transcerebellar diameter. Within each method, agreement of axial and coronal measurements of the transcerebellar diameter was superior in 3D reconstructed MRI compared to 2D conventional MRI (P < .001). CONCLUSIONS: This comparison study validates the use of 3D super-resolution motion-corrected MRI for imaging the fetal posterior fossa, as this technique results in linear measurements that have high concordance with 2D conventional MRI measurements. Lengths of the transcerebellar diameter measured within a 3D reconstruction are more concordant between imaging planes, as they correct for fetal motion and orthogonal slice acquisition. This technique will facilitate further study of fetal abnormalities of the posterior fossa. PMID- 26990620 TI - Brief Report: Changes in Antiphospholipid Antibody Titers During Pregnancy: Effects on Pregnancy Outcomes. AB - OBJECTIVE: To measure variance in antiphospholipid antibody (aPL) levels during pregnancy and to determine if variation affects pregnancy outcomes. METHODS: We used data from the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study, a multicenter prospective study of pregnant women with aPL and/or systemic lupus erythematosus (SLE). Antiphospholipid antibodies were considered present if any of the following were positive: anticardiolipin (aCL), anti-beta2 -glycoprotein I (anti-beta2 GPI) titers >=40 IgG phospholipid (GPL) or IgM phospholipid (MPL) units, and/or lupus anticoagulant (LAC). Antiphospholipid antibodies were measured every trimester and postpartum. Adverse pregnancy outcomes were defined as fetal/neonatal death, preterm delivery (<36 weeks) due to preeclampsia or placental insufficiency, or growth restriction. RESULTS: One hundred fifty-two aPL-positive patients were studied. Fifty-seven percent had clinical antiphospholipid syndrome (APS) and 36% had SLE. IgG aPL levels were significantly lower during the second and third trimesters compared to initial screening, but IgG aCL and anti-beta2 GPI remained high-positive through pregnancy in 93% of patients during the second trimester, and in 85% of patients during the third trimester. IgM aPL titers were negative in the majority of patients and decreased modestly during pregnancy among patients who were positive. LAC frequency also decreased, but 75% of patients remained positive through the second trimester. Only 4% of patients with aPL at baseline did not have aPL in either the second or third trimesters. Changes in aPL levels or aPL status were not associated with adverse pregnancy outcomes. LAC was the only aPL associated with adverse pregnancy outcomes. CONCLUSION: The aPL in the cohort decreased marginally during pregnancy, and changes were not associated with pregnancy outcomes. Our results suggest that, among women with aPL and/or SLE, measuring aPL early in pregnancy is sufficient to assess risk. Repeat aPL testing through pregnancy is unnecessary. PMID- 26990622 TI - Thirty years after the Chernobyl accident - 30 key papers published in the Journal of Environmental Radioactivity. PMID- 26990623 TI - The value of fourth and subsequent post-treatment 18F-FDG PET/CT scans in the management of patients with non-Hodgkin's lymphoma. AB - OBJECTIVE: To evaluate the impact of fourth and subsequent follow-up PET/computed tomography (PET/CT) scans in patients with non-Hodgkins lymphoma (NHL). MATERIALS AND METHODS: This retrospective study evaluated all biopsy-proven NHL patients who had more than three follow-up scans after completion of primary treatment from 2000 to 2013 at our academic center. Among 586 patients with NHL who had at least one fluorine-18 fluorodeoxyglucose (F-FDG) PET/CT scan at our institution, a total of 77 patients with 208 fourth and subsequent follow-up F-FDG PET/CT scans, were included in the study. The impact of these follow-up scans on the clinical assessment and the management of the patients was evaluated. RESULTS: Among 208 fourth and subsequent follow-up scans, 33 were performed with a previous clinical suspicion of recurrence and 175 were performed without a previous clinical suspicion of recurrence. Fourth and subsequent follow-up PET/CT results were useful in excluding tumor in 27.3% of scan times when there was a clinical suspicion of recurrence and in identifying recurrence in 5.1% of scan times when there was no previous clinical suspicion of recurrence. Clinicians changed management after 36.4% (12/33) scans that were performed with previous clinical suspicion of recurrence and 9.2% (16/175) scans that were performed without previous clinical suspicion (P=0.001). CONCLUSION: Fourth and subsequent follow-up PET/CT scans affect the treatment and management of patients with NHL and add value to clinical assessment and management, especially in patients with a previous clinical suspicion of recurrence. PMID- 26990621 TI - A novel protein tyrosine phosphatase 1B inhibitor with therapeutic potential for insulin resistance. AB - BACKGROUND AND PURPOSE: Insulin-sensitizing drugs are currently limited, and identifying new candidates is a challenge. Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling, and its inhibition is anticipated to improve insulin resistance. Here, the pharmacological properties of CX08005, a novel PTP1B inhibitor, were investigated. EXPERIMENTAL APPROACH: Recombinant hPTP1B protein was used to study enzyme activity and mode of inhibition. Docking simulation explored the interactions between CX08005 and PTP1B. Insulin sensitivity was evaluated by glucose tolerance test (GTT) in diet induced obese (DIO) and KKAy mice; glucose-stimulated insulin secretion (GSIS), homeostasis model assessment of insulin resistance index (HOMA-IR) and whole-body insulin sensitivity (ISWB ) were also determined. A hyperinsulinaemic-euglycaemic clamp was performed to evaluate insulin-stimulated glucose disposal in both whole body and insulin-sensitive tissues. Furthermore, CX08005's effects on muscle, fat and liver cells were determined in vitro. KEY RESULTS: CX08005 competitively inhibited PTP1B by binding to the catalytic P-loop through hydrogen bonds. In DIO mice, CX08005 ameliorated glucose intolerance dose-dependently (50-200 mg.kg(-1) .day(-1) ) and decreased the HOMA-IR. In KKAy mice, CX08005 (50 mg.kg(-1) .day( 1) ) improved glucose intolerance, GSIS, ISWB and hyperglycaemia. CX08005 also enhanced insulin-stimulated glucose disposal, increased glucose infusion rate and glucose uptake in muscle and fat in DIO mice (hyperinsulinaemic-euglycaemic clamp test). CX08005 enhanced insulin-induced glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes, and increased phosphorylation of IRbeta/IRS1 and downstream molecules in hepatocytes in a dose- and insulin-dependent manner respectively. CONCLUSIONS AND IMPLICATIONS: Our results strongly suggest that CX08005 directly enhances insulin action in vitro and in vivo through competitive inhibition of PTP1B. PMID- 26990626 TI - Sensitive sentinel mutation screening reveals differential underestimation of transmitted HIV drug resistance among demographic groups. AB - OBJECTIVE: To examine the association of majority and minority-level transmitted HIV drug resistance (TDR) among diverse demographic populations in the United States and assess what different mutations may infer about TDR risk and engagement in care. DESIGN: Used sensitive assays to screen 1070 deidentified convenience plasma specimens from United States national HIV surveillance conducted in 2009-2011 on newly diagnosed persons with no evidence of antiretroviral drug use. METHODS: We applied validated allele-specific PCR for five HIV reverse transcriptase mutations as sentinel markers of TDR. The total and minority-level prevalence of TDR by demographic characteristics was compared. RESULTS: Sensitive screening identified 72% more TDR than conventional sequencing for the five mutations assessed (13.6 vs. 7.9%, P < 0.0001), with K65R having the greatest increase (0-1.7%). One-third of K65R was in persons who also had at least one of the other mutations screened. The total TDR prevalence among whites (16.4%) and blacks (14.9%) was significantly higher than that among Hispanics/Latinos (6.4%) (P = 0.005 and 0.013, respectively). TDR prevalence was highest (23.1%) in those 13-19 years (85% black). TDR prevalence among women (72% black) was nearly as high as among MSM (47% black) (14.3 vs. 15.1%, respectively). CONCLUSION: A significant proportion of TDR, primarily in older, white MSM, was undetected by conventional testing. The greatest underestimation was for rapid-decaying mutations typically associated with the source virus having recent exposure to antiretroviral therapy. However, total TDR prevalence was highest in the less than 20-year age group who were predominantly black, underscoring the importance of prevention efforts for at-risk youth. PMID- 26990627 TI - Association of injection drug use with incidence of HIV-associated non-AIDS related morbidity by age, 1995-2014. AB - OBJECTIVE: Incidence of HIV-associated non-AIDS (HANA) related comorbidities is increasing in HIV-infected individuals. Our objective was to estimate the risk of HANA comorbidity associated with history of injection drug use (IDU) correctly accounting for higher death rates among people who inject drugs (PWID). DESIGN: We followed HIV-infected persons aged 25-59 years who enrolled in the Johns Hopkins HIV Clinical Cohort between 1995 and May 2014, from enrollment until HANA comorbidity diagnosis, death, age 60, or administrative censoring. METHODS: We compared cumulative incidence ('risk'), by age, of validated diagnoses of HANA comorbidities among HIV-infected PWID and non-IDU; specifically, we considered end-stage renal disease (ESRD), end-stage liver disease (ESLD), myocardial infarction, stroke, and non-AIDS-defining cancer. We used competing risk methods appropriate to account for death, standardized to the marginal distribution of baseline covariates, and adjusted for potential differential loss-to-clinic. RESULTS: Of 5490 patients included in this analysis, 37% reported IDU as an HIV transmission risk. By age 55 years, PWID had higher risk of ESLD [risk difference = 6.8, 95% confidence interval (CI): -1.9, 15.5] and ESRD (risk difference = 11.1, 95% CI: 1.2, 21.0) than did non-IDU. Risk of myocardial infarction and stroke were similar among PWID and non-IDU. Risk of non-AIDS-defining cancer was lower among PWID than among non-IDU (risk difference at 55 years: -4.9, 95% CI: 11.2, 1.3). CONCLUSION: Not all HANA comorbidities occur with higher incidence in PWID compared with non-IDU. However, higher incidence of ESRD and ESLD among PWIDs highlights the importance of recognition and management of markers of these comorbidities in early stages among PWID. PMID- 26990628 TI - Interference with purinergic signalling: an explanation for the cardiovascular effect of abacavir? AB - OBJECTIVE: The association of abacavir (ABC), a guanosine analogue, with cardiovascular toxicity is a long-lasting matter of controversy engendered by the lack of a mechanism of action. Clinical data point to an acute mechanism of vascular inflammation. Previous studies have shown that ABC induces leukocyte endothelial cell interactions, an indicator of vascular inflammation. These effects are reproduced by another purine analogue, didanosine, but not by pyrimidine or acyclic nucleotide analogues, hinting at an interference with the purinergic system. The aim of the present study was to assess the role of ATP receptors in leukocyte accumulation induced by ABC. DESIGN AND METHODS: Clinical concentrations of ABC were analysed in an animal model in vivo (intravital microscopy using male C57BL/6 wild-type or P2rx7 knockout mice), in human endothelial cells and leukocytes in vitro (flow chamber), or in leukocyte Mac-1 expression (flow cytometry). RESULTS: ABC reduced leukocyte rolling velocity and increased rolling flux and adhesion both in vivo and in vitro. These effects were absent in P2rx7 knockout mice and following the specific blockade of ATP-P2X7 receptors in wild-type animals. Further pharmacological characterization in flow chamber experiments confirmed the role of ATP-P2X7 receptors and suggested that those located on leukocytes were particularly implicated. Activation of ATP-P2X7 receptors is needed for expression of leukocytic Mac-1. Similar effects were obtained with didanosine. CONCLUSION: ABC induces leukocyte-endothelial cell interactions through a mechanism involving interference with purine-signalling pathways via ATP-P2X7 receptors located mainly on leukocytes. Our data are compatible with existing clinical data revealing an increased cardiovascular risk in ABC-treated patients. PMID- 26990629 TI - Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons. AB - OBJECTIVE: Chronic obstructive pulmonary disease is a common comorbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other comorbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV. DESIGN: Longitudinal observational study. METHODS: Total 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, and TNFalpha), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates. RESULTS: In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse forced expiratory volume in one second (FEV1) percentage-predicted, and higher sCD163 associated with worse FEV1/forced vital capacity. IL-6, TNFalpha, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up. CONCLUSION: Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of chronic obstructive pulmonary disease in HIV-infected persons. PMID- 26990630 TI - Premature aging and immune senescence in HIV-infected children. AB - OBJECTIVE: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. DESIGN: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0-5 years, were studied for biological aging and immune senescence. METHODS: Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4 and CD8 cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. RESULTS: Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8 recent thymic emigrant cells (CD45RACD31) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28CD57), activated (CD38HLA-DR), and exhausted (PD1) CD8 cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4 cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. CONCLUSIONS: HIV infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8 cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatment. PMID- 26990632 TI - Food insecurity is associated with HIV, sexually transmitted infections and drug use among men in the United States. AB - OBJECTIVE: To examine the population-level association between food insecurity, HIV risk factors, and HIV serostatus among men, the group representing the majority of HIV diagnoses in the United States. DESIGN: Cross-sectional secondary data analysis using the National Health and Nutrition Examination Survey 1999 2012, a nationally representative survey of the civilian noninstitutionalized US population. METHODS: Logistic regression with design weights and complex survey commands was used to estimate nationally representative associations between food insecurity and HIV serostatus (primary outcome), herpes simplex virus 2, self reported sexually transmitted infections (STIs), and past-year illicit drug use among men, adjusting for potential confounders. Food security was measured using the 18-item Household Food Security Survey. RESULTS: We analyzed data for 9150 men representing 61 million individuals in the United States. Unadjusted HIV prevalence was 1.5% among food insecure men, compared with 0.4% among food secure men (P < 0.001). In adjusted models, food insecure men had over two times higher odds of HIV seropositivity compared with food secure men [adjusted odds ratio (AOR) = 2.10; 95% confidence interval (CI) 1.01-4.37; P < 0.05]. Food insecurity was associated with higher odds of herpes simplex virus 2 seropositivity (AOR = 1.28; 95% CI 1.04-1.57; P < 0.05), self-reported STIs (AOR = 1.54; 95% CI 1.08 2.20; P < 0.05), and illicit drug use (AOR = 1.57; 95% CI 1.14-2.15; P < 0.01). Results were robust to sensitivity analyses restricted to lower incomes. CONCLUSION: Food insecurity is associated with prevalent HIV, STIs, and illicit drug use among men in the United States. Further research is needed to establish whether and through what mechanisms improved food security may help prevent new HIV infections. PMID- 26990631 TI - Sex differences in soluble markers vary before and after the initiation of antiretroviral therapy in chronically HIV-infected individuals. AB - OBJECTIVE: To evaluate differences in soluble inflammatory markers between chronically HIV-infected men and women, with or without cognitive impairment, and in response to treatment. DESIGN: Soluble biomarkers were measured in cryopreserved plasma and cerebrospinal fluid (CSF) of 60 treatment-naive individuals (25 men and 35 women) with chronic HIV infection and 18 HIV uninfected controls (9 men and 9 women) from Thailand. Following enrollment, participants began combination antiretroviral therapy and were evaluated for expression of these markers after 48 weeks. METHODS: Plasma and CSF levels of 19 soluble biomarkers (IFN-gamma, TNFalpha, TNF-RII, IL-1alpha, IL-1beta, IL-4, IL 5, IL-6, IL-8, IL-10, IL-12p70, IL-15, MCP-1, t-Tau, IP-10, neopterin, IFNalpha, I-FABP, and sCD14) were measured using either a multiparameter or standard ELISA assay. RESULTS: Prior to combination antiretroviral therapy, women with impaired cognition had elevated levels of neopterin and TNF-RII compared with women with normal cognition in both the plasma and CSF; however, levels did not differ between cognitively impaired or normal men. In a secondary outcome-hypothesis generating analysis, sex differences were also pronounced in plasma levels of MCP 1, IL-10, I-FABP, and sCD14 in response to treatment. Neopterin, IP-10, TNFalpha, TNF-RII, IFNalpha, MCP-1, IL-8, I-FABP, and sCD14 plasma levels remained elevated following 48 weeks of therapy in both sexes compared with uninfected controls. CONCLUSION: We provide evidence of sustained immune activation after 48 weeks of treatment and identify possible sex differences in biomarkers previously linked to cognitive impairment, chronic inflammation, and gut integrity that may contribute to immunological differences between sexes in relationship to disease progression and response to therapy. PMID- 26990634 TI - Enhanced hydrogen storage properties of the 2LiBH4-MgH2 composite with BaTiO3 as an additive. AB - The 2LiBH4-MgH2 + 20 wt% BaTiO3 composite was prepared by ball-milling LiBH4, MgH2 and BaTiO3, and the effect of BaTiO3 on the hydrogen storage properties of the composite was investigated. TG-DSC results show that the onset dehydrogenation temperature of the composite is 299 degrees C, which is 124 degrees C lower than that of 2LiBH4-MgH2, and the dehydrogenation amount of the composite increases from 6.86 wt% to 7.48 wt% at 500 degrees C. Kinetic tests show that the dehydrogenation amount of 2LiBH4-MgH2 + 20 wt% BaTiO3 reaches 1.5 wt% within 400 seconds, almost 10 times that of 2LiBH4-MgH2. BaTiO3 reacts with LiBH4 during the dehydrogenation of the composite and generates BaB6 and TiO2. BaB6 is beneficial to lower the stability of LiBH4, while TiO2 has a catalytic effect in improving the hydrogenation/dehydrogenation kinetics of the reaction between Mg and LiBH4. PMID- 26990633 TI - Functional screening of guide RNAs targeting the regulatory and structural HIV-1 viral genome for a cure of AIDS. AB - OBJECTIVE: There is an urgent need for the development of HIV-1 genome eradication strategies that lead to a permanent cure for HIV-1/AIDS. We previously reported that four guide RNAs (gRNAs) targeting HIV-1 long terminal repeats (LTR) effectively eradicated the entire HIV-1 genome. In this study, we sought to identify the best gRNAs targeting HIV-1 LTR and viral structural region and optimize gRNA pairing that can efficiently eradicate the HIV-1 genome. DESIGN: Highly specific gRNAs were designed using bioinformatics tools, and their capacity of guiding CRISPR-associated system 9 to cleave HIV-1 proviral DNA was evaluated using high-throughput HIV-1 luciferase reporter assay and rapid Direct PCR genotyping. METHODS: The target seed sequences for each gRNA were cloned into lentiviral vectors. HEK293T cells were cotransfected with a pEcoHIV-NL4-3-firefly luciferase reporter vector (1 : 20) over lentiviral vectors carrying CRISPR associated system 9 and single gRNA or various combinations of gRNAs. The EcoHIV DNA cleaving efficiency was evaluated by Direct-PCR genotyping, and the EcoHIV transcription/replication activity was examined by a luciferase reporter assay. RESULTS: Most of the designed gRNAs are effective to eliminate the predicted HIV 1 genome sequence between the selected two target sites. This is evidenced by the presence of PCR genotypic deletion/insertion and the decrease of luciferase reporter activity. In particular, a combination of viral structural gRNAs with LTR gRNAs provided a higher efficiency of genome eradication and an easier approach for PCR genotyping. CONCLUSION: Our screening strategy can specifically and effectively identify gRNAs targeting HIV-1 LTR and structural region to excise proviral HIV-1 from the host genome. PMID- 26990635 TI - Human adipose tissue-derived stromal cells can differentiate into megakaryocytes and platelets by secreting endogenous thrombopoietin. AB - Essentials Manufacturing platelets from a donor-independent source is highlighted in transfusion medicine. We examined the differentiation of adipose tissue derived stromal cells (ASCs) into platelets. Endogenous thrombopoietin (TPO) induced ASCs differentiation into megakaryocytes and platelets. TPO secretion from ASCs was due to an interaction of transferrin with its receptor CD71. SUMMARY: Background Ex vivo production of megakaryocytes (MKs) and platelets from a donor-independent source is currently of intense interest in transfusion medicine. Adipose tissue-derived stromal cells (ASCs) constitute an attractive candidate cell source, because inducing these cells into MK lineages requires no gene transfer and only endogenous transcription factors containing p45NF-E2/Maf, an MK-inducing factor. Objectives To examine whether ASCs differentiate into MK lineages by using endogenous thrombopoietin (TPO), a primary cytokine that drives MK lineages. Methods TPO levels were measured by quantitative real-time PCR and ELISA. To investigate the effects of endogenous TPO on MK and platelet production, surface marker expression and functions for platelets were analyzed in ASC-derived cells cultured in the presence or absence of recombinant TPO. Based on a screening test, the role of transferrin receptor CD71 in TPO production and MK differentiation was examined with anti-CD71 antibody, small interfering RNA (siRNA) against CD71 (siRNA-CD71), and CD71-positive/negative cells. Results ASCs secreted TPO during MK differentiation, and the endogenous TPO facilitated MK and platelet production from ASCs. TPO secretion from ASCs occurred in a transferrin-dependent manner. ASCs treated with anti-CD71 antibody or transfected with siRNA-CD71 produced markedly less TPO. The TPO levels and MK yield were significantly higher when CD71-positive ASCs were used than when CD71 negative ASCs were used. Conclusions CD71 might be an appropriate marker for MK progenitor cells among human ASCs, because of the higher capacity of CD71 positive cells to produce TPO and their ability to differentiate into MKs. These findings could help to establish an efficient method for platelet production. PMID- 26990636 TI - RNA versatility governs tRNA function: Why tRNA flexibility is essential beyond the translation cycle. AB - tRNAs undergo multiple conformational changes during the translation cycle that are required for tRNA translocation and proper communication between the ribosome and translation factors. Recent structural data on how destabilized tRNAs utilize the CCA-adding enzyme to proofread themselves put a spotlight on tRNA flexibility beyond the translation cycle. In analogy to tRNA surveillance, this review finds that other processes also exploit versatile tRNA folding to achieve, amongst others, specific aminoacylation, translational regulation by riboswitches or a block of bacterial translation. tRNA flexibility is thereby not restricted to the hinges utilized during translation. In contrast, the flexibility of tRNA is distributed all over its L-shape and is actively exploited by the tRNA interacting partners to discriminate one tRNA from another. Since the majority of tRNA modifications also modulate tRNA flexibility it seems that cells devote enormous resources to tightly sense and regulate tRNA structure. This is likely required for error-free protein synthesis. PMID- 26990638 TI - Correction: Molecular Evidence for Multiple Origins of the European Spined Loaches (Teleostei, Cobitidae). PMID- 26990637 TI - Oriented Growth of Pb1- x Snx Te Nanowire Arrays for Integration of Flexible Infrared Detectors. AB - Assembling nanowires into highly ordered arrays is crucial for developing integration circuits. Oriented growth of mid-infrared Pb1- x Snx Te nanowire arrays on bendable mica, extending the function of existing nanowire arrays, is reported. The flexible photodetectors of these nanowire arrays show a high photoresponsivity of 276 A W(-1) (at 800 nm), which is higher than many previously reported infrared nanosensors. PMID- 26990639 TI - RNA-Seq-Mediated Transcriptome Analysis of a Fiberless Mutant Cotton and Its Possible Origin Based on SNP Markers. AB - As the longest known single-celled trichomes, cotton (Gossypium L.) fibers constitute a classic model system to investigate cell initiation and elongation. In this study, we used a high-throughput transcriptome sequencing technology to identify fiber-initiation-related single nucleotide polymorphism (SNP) markers and differentially expressed genes (DEGs) between the wild-type (WT) Upland cotton (G. hirsutum) Xuzhou 142 and its natural fuzzless-lintless mutant Xuzhou 142 fl. Approximately 700 million high-quality cDNA reads representing over 58 Gb of sequences were obtained, resulting in the identification of 28,610 SNPs--of which 17,479 were novel--from 13,960 expressed genes. Of these SNPs, 50% of SNPs in fl were identical to those of G. barbadense, which suggests the likely origin of the fl mutant from an interspecific hybridization between Xuzhou 142 and an unknown G. barbadense genotype. Of all detected SNPs, 15,555, 12,750, and 305 were classified as non-synonymous, synonymous, and pre-terminated ones, respectively. Moreover, 1,352 insertion/deletion polymorphisms (InDels) were also detected. A total of 865 DEGs were identified between the WT and fl in ovules at 3 and 0 days post-anthesis, with 302 candidate SNPs selected from these DEGs for validation by a high-resolution melting analysis and Sanger sequencing in seven cotton genotypes. The number of genotypic pairwise polymorphisms varied from 43 to 302, indicating that the identified SNPs are reliable. These SNPs should serve as good resources for breeding and genetic studies in cotton. PMID- 26990641 TI - Humidifier Disinfectants Are a Cause of Lung Injury among Adults in South Korea: A Community-Based Case-Control Study. AB - BACKGROUNDS: An outbreak of lung injury among South Korean adults was examined in a hospital-based case-control study, and the suspected cause was exposure to humidifier disinfectant (HD). However, a case-control study with community dwelling controls was needed to validate the previous study's findings, and to confirm the exposure-response relationship between HD and lung injury. METHODS: Each case of lung injury was matched with four community-dwelling controls, according to age (+/-3 years), sex, residence, and history of childbirth since 2006 (for women). Environmental risk factors, which included type and use of humidifier and HD, were investigated using a structured questionnaire during August 2011. The exposure to HD was calculated for both cases and controls, and the corresponding risks of lung injury were compared. RESULTS: Among 28 eligible cases, 16 patients agreed to participate, and 60 matched controls were considered eligible for this study. The cases were more likely to have been exposed to HD (odds ratio: 116.1, 95% confidence interval: 6.5-2,063.7). All cases were exposed to HDs containing polyhexamethyleneguanidine phosphate, and the risk of lung injury increased with the cumulative exposure, duration of exposure, and exposure per day. CONCLUSIONS: This study revealed a statistically significant exposure response relationship between HD and lung injury. Therefore, continuous monitoring and stricter evaluation of environmental chemicals' safety should be conducted. PMID- 26990643 TI - Teaching social play skills to adults and children with autism as an approach to building rapport. AB - Adults with autism spectrum disorder (ASD) and no intellectual disabilities were taught to increase the social play skills of children with ASD as part of a vocational training program. Participants included 3 adults, aged 21 to 27 years, and 6 children with ASD. Probes conducted throughout the study evaluated whether play skills training affected a measure of rapport between the adult and child. Results demonstrated the effectiveness of behavioral skills training for teaching the adult participants the appropriate play skills. In addition, the children's social engagement increased. Finally, rapport probes showed that play skills training increased levels of proximity, our measure of rapport, between the adults and children. PMID- 26990640 TI - Comparative RNA-Seq Analysis Reveals That Regulatory Network of Maize Root Development Controls the Expression of Genes in Response to N Stress. AB - Nitrogen (N) is an essential nutrient for plants, and it directly affects grain yield and protein content in cereal crops. Plant root systems are not only critical for anchorage in the soil, but also for N acquisition. Therefore, genes controlling root development might also affect N uptake by plants. In this study, the responses of nitrogen on root architecture of mutant rtcs and wild-type of maize were investigated by morphological and physiological analysis. Subsequently, we performed a comparative RNA-Seq analysis to compare gene expression profiles between mutant rtcs roots and wild-type roots under different N conditions. We identified 786 co-modulated differentially expressed genes (DEGs) related to root development. These genes participated in various metabolic processes. A co-expression cluster analysis and a cis-regulatory motifs analysis revealed the importance of the AP2-EREBP transcription factor family in the rtcs dependent regulatory network. Some genotype-specific DEGs contained at least one LBD motif in their promoter region. Further analyses of the differences in gene transcript levels between rtcs and wild-type under different N conditions revealed 403 co-modulated DEGs with distinct functions. A comparative analysis revealed that the regulatory network controlling root development also controlled gene expression in response to N-deficiency. Several AP2-EREBP family members involved in multiple hormone signaling pathways were among the DEGs. These transcription factors might play important roles in the rtcs-dependent regulatory network related to root development and the N-deficiency response. Genes encoding the nitrate transporters NRT2-1, NAR2.1, NAR2.2, and NAR2.3 showed much higher transcript levels in rtcs than in wild-type under normal-N conditions. This result indicated that the LBD gene family mainly functions as transcriptional repressors, as noted in other studies. In summary, using a comparative RNA-Seq based approach, we identified DEGs related to root development that also participated in the N-deficiency response in maize. These findings will increase our understanding of the molecular regulatory networks controlling root development and N-stress responses. PMID- 26990644 TI - Building Community Capacity and Fostering Disaster Resilience. AB - OBJECTIVE: To describe, within an ecologically grounded framework, key principles, and recommendations for community-level intervention to build community capacity and promote disaster resilience. METHOD: Using an ecological framework, this article describes community resilience and related constructs and key principles for community-level disaster preparedness and response. RESULTS: Current research suggests the importance of focusing on bolstering resources that promote wellness and facilitate individual and community resilience in the face of disaster. CONCLUSION: We advocate for using an ecological framework grounded in such values as collaboration, social justice, empowerment, and an appreciation of diversity to guide disaster work with communities. We highlight the need to: (a) focus on building community-specific capacity for disaster preparedness, response, and recovery; (b) emphasize increasing the capacity and supportive potential of community members' natural settings to promote wellness; (c) address power and resource inequities; and (d) enhance capacity to ensure contextually and culturally appropriate structures, methods, and interventions. PMID- 26990645 TI - Heterogeneity of Multiple Sclerosis Lesions in Multislice Myelin Water Imaging. AB - PURPOSE: To assess neuroprotection and remyelination in Multiple Sclerosis (MS), we applied a more robust myelin water imaging (MWI) processing technique, including spatial priors into image reconstruction, which allows for lower SNR, less averages and shorter acquisition times. We sought to evaluate this technique in MS-patients and healthy controls (HC). MATERIALS AND METHODS: Seventeen MS patients and 14 age-matched HCs received a 3T Magnetic Resonance Imaging (MRI) examination including MWI (8 slices, 12 minutes acquisition time), T2w and T1mprage pre and post gadolinium (GD) administration. Black holes (BH), contrast enhancing lesions (CEL) and T2 lesions were marked and registered to MWI. Additionally, regions of interest (ROI) were defined in the frontal, parietal and occipital normal appearing white matter (NAWM)/white matter (WM), the corticospinal tract (CST), the splenium (SCC) and genu (GCC) of the corpus callosum in patients and HCs. Mean values of myelin water fraction (MWF) were determined for each ROI. RESULTS: Significant differences (p<=0.05) of the MWF were found in all three different MS-lesion types (BH, CEL, T2 lesions), compared to the WM of HCs. The mean MWF values among the different lesion types were significantly differing from each other. Comparing MS-patients vs. HCs, we found a significant (p<=0.05) difference of the MWF in all measured ROIs except of GCC and SCC. The mean reduction of MWF in the NAWM of MS-patients compared to HCs was 37%. No age, sex, disability score and disease duration dependency was found for the NAWM MWF. CONCLUSION: MWF measures were in line with previous studies and lesions were clearly visible in MWI. MWI allows for quantitative assessment of NAWM and lesions in MS, which could be used as an additional sensitive imaging endpoint for larger MS studies. Measurements of the MWF also differ between patients and healthy controls. PMID- 26990646 TI - Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers. AB - BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded blood oxygenation-level-dependent (BOLD) signals in the brain by functional MRI after infusion of CGRP in a double-blind placebo-controlled crossover study of 27 healthy volunteers. BOLD-signals were recorded in response to noxious heat stimuli in the V1-area of the trigeminal nerve. In addition, we measured BOLD signals after injection of sumatriptan (5-HT1B/1D antagonist). RESULTS: Brain activation to noxious heat stimuli following CGRP infusion compared to baseline resulted in increased BOLD-signal in insula and brainstem, and decreased BOLD signal in the caudate nuclei, thalamus and cingulate cortex. Sumatriptan injection reversed these changes. CONCLUSION: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli. PMID- 26990648 TI - The differential effects of 1,25-dihydroxyvitamin D3 on Salmonella-induced interleukin-8 and human beta-defensin-2 in intestinal epithelial cells. AB - Salmonellosis or Salmonella, one of the most common food-borne diseases, remains a major public health problem worldwide. Intestinal epithelial cells (IECs) play an essential role in the mucosal innate immunity of the host to defend against the invasion of Salmonella by interleukin (IL)-8 and human beta-defensin-2 (hBD 2). Accumulated research has unravelled important roles of vitamin D in the regulation of innate immunity. Therefore, we investigated the effects of 1,25 dihydroxyvitamin D3 (1,25D3) on Salmonella-induced innate immunity in IECs. We demonstrate that pretreatment of 1,25D3 results in suppression of Salmonella induced IL-8 but enhancement of hBD-2, either protein secretion and mRNA expression, in IECs. Furthermore, 1,25D3 enhanced Salmonella-induced membranous recruitment of nucleotide oligomerization domain (NOD2) and its mRNA expression and activation of protein kinase B (Akt), a downstream effector of phosphoinositide 3-kinase (PI3K). Inhibition of the PI3K/Akt signal counteracted the suppressive effect of 1,25D3 on Salmonella-induced IL-8 expression, while knock-down of NOD2 by siRNA diminished the enhanced hBD-2 expression. These data suggest differential regulation of 1,25D3 on Salmonella-induced IL-8 and hBD-2 expression in IECs via PI3K/Akt signal and NOD2 protein expression, respectively. Active vitamin D-enhanced anti-microbial peptide in Salmonella-infected IECs protected the host against infection, while modulation of proinflammatory responses by active vitamin D prevented the host from the detrimental effects of overwhelming inflammation. Thus, active vitamin D-induced innate immunity in IECs enhances the host's protective mechanism, which may provide an alternative therapy for invasive Salmonella infection. PMID- 26990647 TI - Swi1Timeless Prevents Repeat Instability at Fission Yeast Telomeres. AB - Genomic instability associated with DNA replication stress is linked to cancer and genetic pathologies in humans. If not properly regulated, replication stress, such as fork stalling and collapse, can be induced at natural replication impediments present throughout the genome. The fork protection complex (FPC) is thought to play a critical role in stabilizing stalled replication forks at several known replication barriers including eukaryotic rDNA genes and the fission yeast mating-type locus. However, little is known about the role of the FPC at other natural impediments including telomeres. Telomeres are considered to be difficult to replicate due to the presence of repetitive GT-rich sequences and telomere-binding proteins. However, the regulatory mechanism that ensures telomere replication is not fully understood. Here, we report the role of the fission yeast Swi1(Timeless), a subunit of the FPC, in telomere replication. Loss of Swi1 causes telomere shortening in a telomerase-independent manner. Our epistasis analyses suggest that heterochromatin and telomere-binding proteins are not major impediments for telomere replication in the absence of Swi1. Instead, repetitive DNA sequences impair telomere integrity in swi1Delta mutant cells, leading to the loss of repeat DNA. In the absence of Swi1, telomere shortening is accompanied with an increased recruitment of Rad52 recombinase and more frequent amplification of telomere/subtelomeres, reminiscent of tumor cells that utilize the alternative lengthening of telomeres pathway (ALT) to maintain telomeres. These results suggest that Swi1 ensures telomere replication by suppressing recombination and repeat instability at telomeres. Our studies may also be relevant in understanding the potential role of Swi1(Timeless) in regulation of telomere stability in cancer cells. PMID- 26990649 TI - Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular Bioenergetic Function in Breast Cancer Cells. AB - Anacardic acid is a dietary and medicinal phytochemical that inhibits breast cancer cell proliferation and uncouples oxidative phosphorylation (OXPHOS) in isolated rat liver mitochondria. Since mitochondrial-targeted anticancer therapy (mitocans) may be useful in breast cancer, we examined the effect of anacardic acid on cellular bioenergetics and OXPHOS pathway proteins in breast cancer cells modeling progression to endocrine-independence: MCF-7 estrogen receptor alpha (ERalpha)+ endocrine-sensitive; LCC9 and LY2 ERalpha+, endocrine-resistant, and MDA-MB-231 triple negative breast cancer (TNBC) cells. At concentrations similar to cell proliferation IC50 s, anacardic acid reduced ATP-linked oxygen consumption rate (OCR), mitochondrial reserve capacity, and coupling efficiency while increasing proton leak, reflecting mitochondrial toxicity which was greater in MCF-7 compared to endocrine-resistant and TNBC cells. These results suggest tolerance in endocrine-resistant and TNBC cells to mitochondrial stress induced by anacardic acid. Since anacardic acid is an alkylated 2-hydroxybenzoic acid, the effects of salicylic acid (SA, 2-hydroxybenzoic acid moiety) and oleic acid (OA, monounsaturated alkyl moiety) were tested. SA inhibited whereas OA stimulated cell viability. In contrast to stimulation of basal OCR by anacardic acid (uncoupling effect), neither SA nor OA altered basal OCR- except OA inhibited basal and ATP-linked OCR, and increased ECAR, in MDA-MB-231 cells. Changes in OXPHOS proteins correlated with changes in OCR. Overall, neither the 2 hydroxybenzoic acid moiety nor the monounsaturated alky moiety of anacardic acid is solely responsible for the observed mitochondria-targeted anticancer activity in breast cancer cells and hence both moieties are required in the same molecule for the observed effects. J. Cell. Biochem. 117: 2521-2532, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990650 TI - In vivo assessment of riluzole as a potential therapeutic drug for spinocerebellar ataxia type 3. AB - Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly inherited neurodegenerative disorder for which no curative therapy is available. The cause of this disease is the expansion of a CAG repeat in the so-called ATXN3 gene leading to an expanded polyglutamine stretch in the ataxin-3 protein. Although the function of ataxin-3 has been defined as a deubiquitinating enzyme, the pathogenic pathway underlying SCA3 remains to be deciphered. Besides others, also the glutamatergic system seems to be altered in SCA3. The antiglutamatergic substance riluzole has thus been suggested as a potential therapeutic agent for SCA3. To assess whether riluzole is effective in the treatment of SCA3 in vivo, we used a phenotypically well-characterized conditional mouse model previously generated by us. Treatment with 10 mg/kg riluzole in the drinking water was started when mice showed impairment in rotarod performance. Post-symptomatic treatment with riluzole carried out for a period of 10 months led to reduction of the soluble ataxin-3 level and an increase in ataxin-3 positive accumulations, but did not improve motor deficits measured by rotarod. There was also no positive effect on home cage behavior or body weight. We even observed a pronounced reduction of calbindin expression in Purkinje cells in riluzole treated mice. Thus, long-term treatment with riluzole was not able to alleviate disease symptoms observed in transgenic SCA3 mice and should be considered with caution in the treatment of human patients. Assessing riluzole as a potential treatment for spinocerebellar ataxia type 3 (SCA3) had no beneficial, but rather a worsening effect on our transgenic SCA3 mouse model. We hypothesize that: Riluzole treatment enhanced glutamate release in ATXN3-expressing cells leading to an increased Ca(2+) influx resulting in Purkinje cell damage shown by loss of calbindin expression. PMID- 26990651 TI - Relearning of Writing Skills in Parkinson's Disease After Intensive Amplitude Training. AB - BACKGROUND: Micrographia occurs in approximately 60% of people with Parkinson's disease (PD). Although handwriting is an important task in daily life, it is not clear whether relearning and consolidation (ie the solid storage in motor memory) of this skill is possible in PD. The objective was to conduct for the first time a controlled study into the effects of intensive motor learning to improve micrographia in PD. METHODS: In this placebo-controlled study, 38 right-handed people with PD were randomized into 2 groups, receiving 1 of 2 equally time intensive training programs (30 min/day, 5 days/week for 6 weeks). The experimental group (n = 18) performed amplitude training focused at improving writing size. The placebo group (n = 20) received stretch and relaxation exercises. Participants' writing skills were assessed using a touch-sensitive writing tablet and a pen-and-paper test, pre- and posttraining, and after a 6 week retention period. The primary outcome was change in amplitude during several tests of consolidation: (1) transfer, using trained and untrained sequences performed with and without target zones; and (2) automatization, using single- and dual-task sequences. RESULTS: The group receiving amplitude training significantly improved in amplitude and variability of amplitude on the transfer and automatization task. Effect sizes varied between 7% and 17%, and these benefits were maintained after the 6-week retention period. Moreover, there was transfer to daily life writing. CONCLUSIONS: These results show automatization, transfer, and retention of increased writing size (diminished micrographia) after intensive amplitude training, indicating that consolidation of motor learning is possible in PD. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26990652 TI - Thoughts on anaesthesia in chronobiological studies with electrocardiograms. PMID- 26990653 TI - Chermesins A-D: Meroterpenoids with a Drimane-Type Spirosesquiterpene Skeleton from the Marine Algal-Derived Endophytic Fungus Penicillium chermesinum EN-480. AB - Chermesins A-D (1-4), four new spiromeroterpenoids containing a drimane-type sesquiterpene skeleton, were isolated and identified from the culture extract of Penicillium chermesinum EN-480, an endophytic fungus obtained from the inner tissue of the marine red alga Pterocladiella tenuis. The structures of these new spiromeroterpenoids were elucidated based on detailed spectroscopic analyses, and their absolute configurations were confirmed by single-crystal X-ray diffraction experiments and by ECD data. This is the first report of the crystal structures of spiromeroterpenoids that contain a drimane-type sesquiterpene skeleton with a rare cyclohexa-2,5-dienone unit, which resulted in the unambiguous assignment of their relative and absolute configurations. Compounds 1 and 2 exhibited antibacterial activity against the opportunistic pathogen Micrococcus luteus, with an MIC value of 8 MUg/mL. PMID- 26990654 TI - Performance evaluation of four rapid antigen tests for the detection of Respiratory syncytial virus. AB - Rapid identification of Respiratory syncytial virus (RSV) is important in the management of infected patients. Rapid diagnostic tests (RDT) are widely used for this purpose. This study aimed to evaluate the clinical performance of four RSV antigen tests including the BinaxNow RSV Card test, SD Bioline RSV test, BD Veritor RSV test, and Humasis RSV antigen test in comparison with real-time RT PCR as the reference method. Nasopharyngeal swabs were collected from 280 patients with symptoms of lower respiratory tract infection and stored at -80 degrees C. All swabs were tested for RSV using four rapid antigen tests and real time RT-PCR. The sensitivity of the BinaxNow RSV Card test, SD Bioline RSV test, BD Veritor RSV test, and Humasis RSV Antigen tests were 62.5%, 61.3%, 65.0%, and 67.5% for RSV A, and 61.3%, 65.0%, 61.3%, and 67.5% for RSV B compared to real time RT-PCR, respectively. The specificity of BD Veritor RSV test was 95.8% and those of the other three RDTs was 100%. Commercial RSV antigen detection assays are useful tools for the rapid diagnosis of RSV infection. However, confirmatory testing is always recommended. J. Med. Virol. 88:1720-1724, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990655 TI - Multiple imputation methods for bivariate outcomes in cluster randomised trials. AB - Missing observations are common in cluster randomised trials. The problem is exacerbated when modelling bivariate outcomes jointly, as the proportion of complete cases is often considerably smaller than the proportion having either of the outcomes fully observed. Approaches taken to handling such missing data include the following: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We contrasted the alternative approaches to handling missing data in a cost-effectiveness analysis that uses data from a cluster randomised trial to evaluate an exercise intervention for care home residents. We then conducted a simulation study to assess the performance of these approaches on bivariate continuous outcomes, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. Across all the missing data mechanisms considered, the multiple imputation methods provided estimators with negligible bias, while complete case analysis resulted in biased treatment effect estimates in scenarios where the randomised treatment arm was associated with missingness. Confidence interval coverage was generally in excess of nominal levels (up to 99.8%) following fixed-effects multiple imputation and too low following single-level multiple imputation. Multilevel multiple imputation led to coverage levels of approximately 95% throughout. (c) 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID- 26990656 TI - Pharmacokinetics of nebulized and oral procaterol in asthmatic and non-asthmatic subjects in relation to doping analysis. AB - The purpose of the present study was to investigate pharmacokinetics of procaterol in asthmatics and non-asthmatics after nebulized and oral administration in relation to doping. Ten asthmatic and ten non-asthmatic subjects underwent two pharmacokinetic trials. At first trial, 4 ug procaterol was administered as nebulization. At second trial, 100 ug procaterol was administered orally. Serum and urine samples were collected before and after administration of procaterol. Samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum and urine concentrations of procaterol were markedly higher after oral administration compared to nebulized administration. After oral administration, serum procaterol concentration-time area under the curve (AUC) was higher (P <= 0.05) for asthmatics than non asthmatics. Likewise, urine concentrations were higher (P <= 0.01) for asthmatics than non-asthmatics 4 (47 +/- 12 vs. 28 +/- 9 ng/mL) and 8 h (39 +/- 9 vs. 15 +/- 5 ng/mL) after oral administration. Detection of serum procaterol was difficult after nebulized administration with 38 samples (27%) below limit of quantification (LOQ) and only trends were observed. No differences were observed between asthmatics and non-asthmatics in the urine concentrations of procaterol after nebulized administration. In summary, our data showed that asthmatics had higher urine concentrations of procaterol than non-asthmatics after oral administration of 100 ug, whereas no difference was observed between the groups after nebulized administration. For doping control purposes, our observations indicate that it is possible to differentiate therapeutic nebulized administration of procaterol from prohibited use of oral procaterol. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990657 TI - Are hand preference and sexual orientation possible predicting factors for finasteride adverse effects in male androgenic alopecia? AB - Sexual side effects of finasteride seem to be redoubtable, being encountered not only during therapy but also after treatment cessation. Consequently, any possible clinical/paraclinical elements that might predict these adverse effects would be useful in the selection of a therapeutic strategy for male androgenic alopecia. Previous published studies show that some compounds that interfere with sexual hormones can decrease sexual activation and response, according to hand preference (as reported for finasteride and tamoxifen) and according to sexual orientation (as noted for bicalutamide). Our preliminary published data and the arguments presented here suggest that these two individual parameters might be used by dermatologists in the therapeutic approach of male androgenic alopecia, so as to alert specific subsets of men, prior to treatment, of the potential increased risk for developing adverse effects to finasteride. PMID- 26990659 TI - Ly6C(+) monocyte efferocytosis and cross-presentation of cell-associated antigens. AB - Recently it was shown that circulating Ly6C(+) monocytes traffic from tissue to the draining lymph nodes (LNs) with minimal alteration in their overall phenotype. Furthermore, in the steady state, Ly6C(+) monocytes are as abundant as classical dendritic cells (DCs) within the draining LNs, and even more abundant during inflammation. However, little is known about the functional roles of constitutively trafficking Ly6C(+) monocytes. In this study we investigated whether Ly6C(+) monocytes can efferocytose (acquire dying cells) and cross present cell-associated antigen, a functional property particularly attributed to Batf3(+) DCs. We demonstrated that Ly6C(+) monocytes intrinsically efferocytose and cross-present cell-associated antigen to CD8(+) T cells. In addition, efferocytosis was enhanced upon direct activation of the Ly6C(+) monocytes through its corresponding TLRs, TLR4 and TLR7. However, only ligation of TLR7, and not TLR4, enhanced cross-presentation by Ly6C(+) monocytes. Overall, this study outlines two functional roles, among others, that Ly6C(+) monocytes have during an adaptive immune response. PMID- 26990660 TI - Identification of a novel agrin-dependent pathway in cell signaling and adhesion within the erythroid niche. AB - Establishment of cell-cell adhesion is crucial in embryonic development as well as within the stem cell niches of an adult. Adhesion between macrophages and erythroblasts is required for the formation of erythroblastic islands, specialized niches where erythroblasts proliferate and differentiate to produce red blood cells throughout life. The Eph family is the largest known family of receptor tyrosine kinases (RTKs) and controls cell adhesion, migration, invasion and morphology by modulating integrin and adhesion molecule activity and by modifying the actin cytoskeleton. Here, we identify the proteoglycan agrin as a novel regulator of Eph receptor signaling and characterize a novel mechanism controlling cell-cell adhesion and red cell development within the erythroid niche. We demonstrate that agrin induces clustering and activation of EphB1 receptors on developing erythroblasts, leading to the activation of alpha5beta1 integrins. In agreement, agrin knockout mice display severe anemia owing to defective adhesion to macrophages and impaired maturation of erythroid cells. These results position agrin-EphB1 as a novel key signaling couple regulating cell adhesion and erythropoiesis. PMID- 26990658 TI - PPARgamma neddylation essential for adipogenesis is a potential target for treating obesity. AB - The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator activated receptor gamma (PPARgamma) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARgamma is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARgamma, leading to PPARgamma stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARgamma signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARgamma. PMID- 26990662 TI - Reciprocal regulation of miRNAs and piRNAs in embryonic development. AB - MicroRNAs (miRNAs) and piwi-interacting RNAs (piRNAs) are two classes of small noncoding RNAs, both of which play roles in regulating tissue development. It is unknown whether these distinct classes of noncoding RNAs can regulate one another. Here we show that ectopic expression of miR-17 inhibited mouse fertility and early embryonic development. Specifically, we found that the piRNA amplification loop was repressed by miR-17-5p, leading to increased levels of transposition mutagenesis. This occurred by suppressing the amplification loop of piRNAs with an identical 5' sequence and by targeting Mili/Miwi2, an essential component of the piRNA amplification loop, and the DNA methyltransferase, Dnmt3a. We also found that increased levels of piRNAs could compete with miRNAs for target binding, resulting in increased expression of Dnmt3a and Mili. Increased Dnmt3a levels could in turn block miR-17-5p expression, while increased Mili expression could accelerate piRNA amplification and inhibit transposon generation, favoring embryonic development. We report for the first time the reciprocal regulation between miRNAs and piRNAs in mouse embryonic development. PMID- 26990664 TI - Temperature dependence of strain energy and thermodynamic properties of V2 O5 based single-walled nanotubes: Zone-folding approach. AB - A zone-folding approach is applied to estimate the thermodynamic properties of V2 O5 -based nanotubes. The results obtained are compared with those from the direct calculations. It is shown that the zone-folding approximation allows an accurate estimation of nanotube thermodynamic properties and gives a gain in computation time compared to their direct calculations. Both approaches show that temperature effects do not change the relative stability of V2 O5 free layers and nanotubes derived from the alpha- and gamma-phase. The internal energy thermal contributions into the strain energy of nanotubes are small and can be ignored. (c) 2016 Wiley Periodicals, Inc. PMID- 26990663 TI - Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages. AB - The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes involved in shaping adaptive immune responses, but their role in innate immune signaling is still elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages, highly specialized tissue macrophages of the alveolar lung surface. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNgamma transcriptionally induced all three immunoproteasome subunits, low molecular mass protein 2 (LMP2), LMP7 and multicatalytic endopeptidase complex-like 1, which was accompanied by increased immunoproteasome activity in M1 cells. Deficiency of LMP7 had no effect on the LPS/IFNgamma-triggered M1 profile indicating that immunoproteasome function is dispensable for classical alveolar macrophage activation. In contrast, IL-4 triggered alternative (M2) activation of primary alveolar macrophages was accompanied by a transcriptionally independent amplified expression of LMP2 and LMP7 and an increase in immunoproteasome activity. Alveolar macrophages from LMP7 knockout mice disclosed a distorted M2 profile upon IL-4 stimulation as characterized by increased M2 marker gene expression and CCL17 cytokine release. Comparative transcriptome analysis revealed enrichment of IL-4-responsive genes and of genes involved in cellular response to defense, wounding and inflammation in LMP7-deficient alveolar macrophages indicating a distinct M2 inflammation resolving phenotype. Moreover, augmented M2 polarization was accompanied by amplified AKT/STAT6 activation and increased RNA and protein expression of the M2 master transcription factor interferon regulatory factor 4 in LMP7(-/-) alveolar macrophages. IL-13 stimulation of LMP7-deficient macrophages induced a similar M2 skewed profile indicative for augmented signaling via the IL-4 receptor alpha (IL4Ralpha). IL4Ralpha expression was generally elevated only on protein but not RNA level in LMP7(-/-) alveolar macrophages. Importantly, specific catalytic inhibition with an LMP7-specific proteasome inhibitor confirmed augmented IL-4 mediated M2 polarization of alveolar macrophages. Our results thus suggest a novel role of immunoproteasome function for regulating alternative activation of macrophages by limiting IL4Ralpha expression and signaling. PMID- 26990665 TI - Reply. PMID- 26990661 TI - The clearance of dying cells: table for two. AB - Phagocytic cells of the immune system must constantly survey for, recognize, and efficiently clear the billions of cellular corpses that arise as a result of development, stress, infection, or normal homeostasis. This process, termed efferocytosis, is critical for the prevention of autoimmune and inflammatory disorders, and persistence of dead cells in tissue is characteristic of many human autoimmune diseases, notably systemic lupus erythematosus. The most notable characteristic of the efferocytosis of apoptotic cells is its 'immunologically silent' response. Although the mechanisms by which phagocytes facilitate engulfment of dead cells has been a well-studied area, the pathways that coordinate to process the ingested corpse and direct the subsequent immune response is an area of growing interest. The recently described pathway of LC3 (microtubule-associated protein 1A/1B-light chain 3)-associated phagocytosis (LAP) has shed some light on this issue. LAP is triggered when an extracellular particle, such as a dead cell, engages an extracellular receptor during phagocytosis, induces the translocation of autophagy machinery, and ultimately LC3 to the cargo-containing phagosome, termed the LAPosome. In this review, we will examine efferocytosis and the impact of LAP on efferocytosis, allowing us to reimagine the impact of the autophagy machinery on innate host defense mechanisms. PMID- 26990666 TI - Screening for Intimate Partner Violence. AB - Intimate partner violence (IPV) is a serious concern for women that is associated with significant adverse health effects. Routine screening for IPV is recommended, but there are many barriers to screening that have been identified by providers, including discomfort, lack of training, and not knowing how to respond to a positive screen. This article reviews IPV screening and appropriate techniques for responding to a positive screen. IPV screening best practices include using a systematic protocol, developing a screening script, using a validated screening tool, and considerations for privacy and mandatory reporting. Responding to a positive screen should include acknowledging the experience, asking if the woman desires help, offering support and referrals, encouraging safety planning, and completing additional assessments to determine level of danger and to identify any comorbidities. Using these techniques along with therapeutic communication may increase IPV identification and create an environment in which women feel empowered to get help. PMID- 26990669 TI - Health Systems Research Consortia and the Promotion of Health Equity in Low and Middle-Income Countries. AB - Health systems research is widely identified as an indispensable means to achieve the goal of health equity between and within countries. Numerous health systems research consortia comprised of institutions from high-income countries and low and middle-income countries (LMICs) are currently undertaking programs of research in LMICs. These partnerships differ from collaborations that carry out single projects in the multiplicity of their goals, scope of their activities, and nature of their management. Recent conceptual work has explored what features might be necessary for health systems research consortia and their research programs to promote health equity. Identified features include selecting research priorities that focus on improving access to high-quality health services and/or financial protection for disadvantaged populations in LMICs and conducting research capacity strengthening that promotes the independent conduct of health systems research in LMICs. Yet, there has been no attempt to investigate whether existing consortia have such characteristics. This paper describes the results of a survey undertaken with health systems research consortia leaders worldwide to assess how consistent current practice is with the proposed ethical guidance. The findings suggest that consortia may be fairly well organised to promote health equity, but have scope for improvement, particularly in terms of achieving inclusive priority-setting. PMID- 26990667 TI - Characterization of the Binding of Hydroxyindole, Indoleacetic acid, and Morpholinoaniline to the Salmonella Type III Secretion System Proteins SipD and SipB. AB - Many Gram-negative bacteria require the type III secretion system (T3SS) to cause infectious diseases in humans. A looming public health problem is that all bacterial pathogens that require the T3SS to cause infectious diseases in humans have developed multidrug resistance to current antibiotics. The T3SS is an attractive target for the development of new antibiotics because of its critical role in virulence. An initial step in developing anti-T3SS-based therapeutics is the identification of small molecules that can bind to T3SS proteins. Currently, the only small molecules that are known to bind to the Salmonella T3SS proteins SipD and SipB are bile salts (to SipD) and sphingolipids and cholesterol (to SipB). Herein we report the results of a surface plasmon resonance screen of 288 compounds wherein the binding of 4-morpholinoaniline to SipD, 3-indoleacetic acid to SipB, and 5-hydroxyindole to both SipD and SipB were identified. We also identified by NMR the SipD surfaces involved in binding. These three compounds represent a new class of molecules that can bind to T3SS tip (SipD) and translocon (SipB) proteins that could find use in future drug design. PMID- 26990668 TI - Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases: an update meta-analysis. AB - Brain metastasis (BM) is the common complication of non-small cell lung cancer (NSCLC) with a poor prognosis and dismal survival rate. This update meta-analysis aimed to derive a more precise estimation of radiotherapy plus epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC patients with BM. PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Library were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using STATA Version 12.0. In total, 15 studies involving 1552 participants were included. The results indicated that radiotherapy plus EGFR TKIs was more effective at improving response rate and disease control rate (DCR) (risk ratio (RR) = 1.48, 95% confidence interval [CI]: 1.12-1.96, P = 0.005; RR = 1.29, 95% CI: 1.02-1.60, P = 0.035; respectively) than radiotherapy alone or plus chemotherapy. Moreover, radiotherapy plus EGFR TKIs significantly prolonged the time to central nervous system progression (CNS-TTP) (HR = 0.56, 95% CI [0.33, 0.80]; P = 0.000) and median overall survival (OS) (HR = 0.58, 95% CI [0.42, 0.74]; P = 0.000) but significantly increased adverse events (any grade) (RR = 1.25, 95% CI [1.01, 1.57]; P = 0.009), especially rash and dry skin. These results suggested that radiotherapy plus EGFR TKIs produced superior response rate and DCR and markedly prolonged the CNS-TTP and OS of NSCLC patients with BM. However, combined groups had the higher rate of incidence of overall adverse effects, especially rash and dry skin. PMID- 26990670 TI - Catalytic Asymmetric Cycloaddition of In Situ-Generated ortho-Quinone Methides and Azlactones by a Triple Bronsted Acid Activation Strategy. AB - A convergent and highly stereoselective [4+2] cycloaddition of in situ-generated ortho-Quinone methides (o-QMs) and azlactone enols has been successfully developed through a triple Bronsted acid catalysis strategy. This protocol provides an efficient and mild access to various densely functionalized dihydrocoumarins bearing adjacent quaternary and tertiary stereogenic centers in high yields with excellent diastereo- and enantioselectivity. PMID- 26990671 TI - Modelling marine community responses to climate-driven species redistribution to guide monitoring and adaptive ecosystem-based management. AB - As a consequence of global climate-driven changes, marine ecosystems are experiencing polewards redistributions of species - or range shifts - across taxa and throughout latitudes worldwide. Research on these range shifts largely focuses on understanding and predicting changes in the distribution of individual species. The ecological effects of marine range shifts on ecosystem structure and functioning, as well as human coastal communities, can be large, yet remain difficult to anticipate and manage. Here, we use qualitative modelling of system feedback to understand the cumulative impacts of multiple species shifts in south eastern Australia, a global hotspot for ocean warming. We identify range-shifting species that can induce trophic cascades and affect ecosystem dynamics and productivity, and evaluate the potential effectiveness of alternative management interventions to mitigate these impacts. Our results suggest that the negative ecological impacts of multiple simultaneous range shifts generally add up. Thus, implementing whole-of-ecosystem management strategies and regular monitoring of range-shifting species of ecological concern are necessary to effectively intervene against undesirable consequences of marine range shifts at the regional scale. Our study illustrates how modelling system feedback with only limited qualitative information about ecosystem structure and range-shifting species can predict ecological consequences of multiple co-occurring range shifts, guide ecosystem-based adaptation to climate change and help prioritise future research and monitoring. PMID- 26990672 TI - Breastfeeding booklet and proactive phone calls for increasing exclusive breastfeeding rates: RCT protocol. AB - Breastfeeding is associated with infant and maternal health benefits and considerable potential savings to health services. Despite this, only 37% of infants globally are exclusively breastfed for 6 months. Interventions are needed to improve breastfeeding rates. The aim of this study is to determine whether written breastfeeding information in pregnancy and proactive breastfeeding focused support phone calls, provided by a health professional educated in breastfeeding management, increase exclusive breastfeeding rates at 3 months compared with general birth-related information with proactive support calls or standard care. This is a single-centre, randomised, controlled, three-arm, superiority study with blind outcome assessment. Eligible participants will include primigravidae with singleton pregnancies who speak Croatian, attending six primary care obstetric practices. We estimate a total sample size of 459, with computer generated stratified randomisation of 153 women per arm. Participants in the intervention and active control groups will receive booklets in pregnancy, phone calls 2 weeks later, and 2, 6 and 10 weeks after birth. The primary outcome will be the proportion of women exclusively breastfeeding at 3 months. Secondary outcomes will compare: infant feeding practices and attitudes, social support, breastfeeding difficulties, breastfeeding self efficacy and utilisation of breastfeeding support services. Follow-up at 6 months will compare exclusive and any breastfeeding and utilised support services. Analysis will be by intention to treat. This trial will contribute to future evidence syntheses identifying the most effective forms of breastfeeding support. PMID- 26990673 TI - Evaluation of a pharmacist-led hypertension preventative and detection service in the Ghanaian community pharmacy: an exploratory study. AB - OBJECTIVES: The objective of the study was to explore the feasibility and acceptability of a pharmacist-led hypertension preventative service in the community pharmacy. METHODS: This was an exploratory uncontrolled pre-post intervention study conducted from February 2012 - March 2013 in three community pharmacies in Ghana. Clients at risk for hypertension were identified and screened by the Medicine Counter Assistant (MCA). Those whose blood pressure was above 140/90 (stage 1 and 2 hypertension) were referred to the pharmacist for further assessment and referral to the physician as necessary. Participant awareness of risk and changes in the lifestyle was assessed at baseline and 6 month follow-up respectively. KEY FINDINGS: Out of 250 clients approached, 170 agreed to be screened. Forty three (25%) were pre-hypertensive, 42 (25%) had stage 1 hypertension and 13 (8%) had stage 2 hypertension. The most frequent modifiable risk factors identified were lack of exercise 107 (63%), poor diet (42%) and obesity (21%). Lifestyle changes reported at 6 months by participants with pre-hypertension were weight reduction and reduced alcohol intake. Of the 34 participants who were referred to the physician, 10 (29%) were diagnosed with hypertension and an antihypertensive was prescribed. CONCLUSIONS: Hypertension preventative services offered in the Ghanaian community pharmacy are acceptable to clients. The findings suggest that pharmacists can detect hypertension and promote some lifestyle changes among clients with pre-hypertension. A larger controlled study is needed to confirm these findings. Ultimately guidelines and polices to streamline these services would be needed if such services were made routinely available in community pharmacies in Ghana. PMID- 26990674 TI - Darier's disease and rheumatoid arthritis: a new association and a review of the literature. PMID- 26990676 TI - Estimation of the prevalence and direct medical costs of chronic myeloid leukemia in the I.R. of Iran in the era of tyrosine kinase inhibitors. AB - BACKGROUND: After the introduction of tyrosine kinase inhibitors for chronic myeloid leukemia (CML), the survival of these patients has increased significantly. However, these new drugs are expensive and impose considerable expense to patients and governments. Epidemiologic and economic evaluation studies provide good information for resource allocation and decision making. We estimated the incidence, prevalence and direct medical cost of CML in Iran. METHODS: We used the National Cancer Registry (NCR) data from 2006 to 2009 to estimate the incidence rate of CML (ICD-10 code C92.1). After adjustment for the underestimation of incidence rates, we used survival rates of CML and estimated the 5-year prevalence for these patients. In addition, we used clinical practice guideline, expert opinions and medical tariffs to estimate the direct medical costs through the prevalence approach. RESULTS: After an adjustment for the underestimation, the incidence rate of CML was 0.5 per 100 000 in the I.R. of Iran. The 5-year prevalence was about 2263 cases (2.98 per 100 000). The total direct medical cost of CML was $23 089 323 and the majority of the cost (97%) was related to drug costs. The total cost will increase considerably to $40 728 869 if all patients use the new drug nilotinib (800 mg/day) as a second-line treatment. CONCLUSIONS: The increased survival of CML patients and a possible increase in incidence of CML in Iran will most likely lead to a considerable rise in its prevalence and economic burden. PMID- 26990675 TI - Psychopathic traits mediate the association of serotonin transporter genotype and child externalizing behavior. AB - Although the promoter polymorphism of the serotonin transporter (5-HTTLPR) gene is associated with externalizing behavior, its mediating pathways are unknown. Given their sensitivity to serotonin neurotransmission and unique association with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), we tested callous-unemotional (CU) traits and narcissism as separate mediators of the association of 5-HTTLPR with ADHD and ODD. We evaluated 209 5-9 year-old children with and without ADHD at baseline; approximately 2 years later (i.e., Wave 2), parents and teachers separately rated ADHD and ODD symptoms and youth self-reported antisocial behavior. Controlling for race ethnicity and baseline ADHD/ODD, narcissism uniquely mediated predictions of multi-informant rated Wave 2 ADHD and ODD from variation in 5-HTTLPR; CU traits mediated predictions of Wave 2 ADHD from variations in 5-HTTLPR, but did not mediate the associations of 5-HTTLPR with ODD or youth self-reported antisocial behavior. Specifically, the number of 5-HTTLPR long alleles positively predicted CU traits and narcissism; narcissism was positively associated with Wave 2 ADHD and ODD symptoms, whereas CU traits were positively associated with Wave 2 ADHD. Child sex also moderated indirect effects of CU traits and narcissism, such that narcissism mediated predictions of ADHD/ODD in girls but not boys. Psychopathic traits may represent a relevant pathway underlying predictions of prospective change in ADHD and ODD from 5-HTTLPR, particularly in girls. We consider the role of psychopathic traits as a potential intermediate phenotype in genetically sensitive studies of child psychopathology. Aggr. Behav. 42:455-470, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990677 TI - Hematopoietic stem cell transplantation: Improving alloreactive Bw4 donor selection by genotyping codon 86 of KIR3DL1/S1. AB - KIR3DL1 is a natural killer (NK) cell receptor that recognizes the Bw4 epitope of human leukocyte antigen (HLA) class I molecules. Following hematopoietic stem cell transplantation for patients lacking Bw4, KIR3DL1-expressing NK cells from Bw4-positive donors can be alloreactive and eliminate tumor cells. However, KIR3DL1 alleles having T instead of C at nucleotide 320 (encoding leucine 86 instead of serine 86) are not expressed on the cell surface. Thus, not all individuals testing positive for KIR3DL1 are optimal donors for Bw4-negative recipients. Therefore, we developed a method for genotyping codon 86, which was validated by its perfect correlation with NK cell phenotype for 100 donors of diverse KIR3DL1/S1 genotype. We typed 600 donors and found that ~12.2% had the KIR3DL1 gene, but did not express cell-surface KIR3DL1. By contrast, high expressing allotypes were identified when haplotypes from four families with duplicated KIR3DL1/S1 genes were characterized at high resolution. Identifying donors who have KIR3DL1 but lack cell-surface KIR3DL1 would refine donor selection. With this technique, the number of individuals identified who may not be optimal donors for Bw4-negative patients increases by threefold, when compared with standard methods. Taken together, we propose that allele typing of killer cell Ig-like receptor (KIR) polymorphisms should become a standard practice when selecting donors. PMID- 26990678 TI - Cost-effectiveness of preventing dental caries and full mouth dental reconstructions among Alaska Native children in the Yukon-Kuskokwim delta region of Alaska. AB - OBJECTIVE: We conducted a cost-effectiveness analysis of five specific dental interventions to help guide resource allocation. METHODS: We developed a spreadsheet-based tool, from the healthcare payer perspective, to evaluate the cost effectiveness of specific dental interventions that are currently used among Alaska Native children (6-60 months). Interventions included: water fluoridation, dental sealants, fluoride varnish, tooth brushing with fluoride toothpaste, and conducting initial dental exams on children <18 months of age. We calculated the cost-effectiveness ratio of implementing the proposed interventions to reduce the number of carious teeth and full mouth dental reconstructions (FMDRs) over 10 years. RESULTS: A total of 322 children received caries treatments completed by a dental provider in the dental chair, while 161 children received FMDRs completed by a dental surgeon in an operating room. The average cost of treating dental caries in the dental chair was $1,467 (~258,000 per year); while the cost of treating FMDRs was $9,349 (~1.5 million per year). All interventions were shown to prevent caries and FMDRs; however tooth brushing prevented the greatest number of caries at minimum and maximum effectiveness with 1,433 and 1,910, respectively. Tooth brushing also prevented the greatest number of FMDRs (159 and 211) at minimum and maximum effectiveness. CONCLUSIONS: All of the dental interventions evaluated were shown to produce cost savings. However, the level of that cost saving is dependent on the intervention chosen. PMID- 26990680 TI - New choices, new challenges: Anti-TNF versus anti-integrin molecule therapy in IBD. PMID- 26990679 TI - The Establishment of an HE4-CLIA Method and the Combined Analysis of HE4 and CA125 in Ovarian Cancer. AB - BACKGROUND: The human epididymal secretory protein 4 (HE4) is a novel, verified biomarker for the early diagnosis of ovarian cancer. METHODS: Magnetic beads were coated with capture antibodies and were used with acridinium ester labeled detection antibodies in a sandwich-type immunoassay. The patient's HE4 serum levels were measured simultaneously with the chemiluminescence immunoassay (CLIA) kit we developed and electrochemiluminescence immunoassay (ECLIA) kit from Roche (Mannheim, Germany). CA125 was also detected by time-resolved fluoroimmunoassay. The diagnostic value was analyzed. RESULTS: The assay demonstrated a linear range from 2.5 to 2,000 pmol/l, with an analytical sensitivity of 2.5 pmol/l. The reproducibility, recovery, and specificity of the immunoassay were demonstrated to be acceptable. Compared with the ECLIA kit from Roche in 124 serum samples (40 patients with ovarian cancer, 35 patients with benign gynecological diseases, and 49 health controls), there is a satisfied correlation coefficient of 0.875. The area under the receiver-operating curve (ROC-AUC) was 0.903 (95% CI was 0.839 0.966, P < 0.001) for HE4, 0.787 (95% CI was 0.694-0.879, P < 0.001) for CA125, and 0.914 (95% CI was 0.866-0.962, P < 0.001) for combined analysis of HE4 and CA125. CONCLUSIONS: A quantitative method (HE4-CLIA) for detecting HE4 in serum was successfully established. Preliminary clinical sample analysis showed HE4 CLIA has a certain clinical value in the screening and diagnosis of ovarian cancer. Moreover, in distinguishing benign from malignant ovarian lesions, HE4 has higher demonstrated accuracy than CA125. PMID- 26990681 TI - The homeodomain transcription factor TaHDZipI-2 from wheat regulates frost tolerance, flowering time and spike development in transgenic barley. AB - Homeodomain leucine zipper class I (HD-Zip I) transcription factors (TFs) play key roles in the regulation of plant growth and development under stresses. Functions of the TaHDZipI-2 gene isolated from the endosperm of developing wheat grain were revealed. Molecular characterization of TaHDZipI-2 protein included studies of its dimerisation, protein-DNA interactions and gene activation properties using pull-down assays, in-yeast methods and transient expression assays in wheat cells. The analysis of TaHDZipI-2 gene functions was performed using transgenic barley plants. It included comparison of developmental phenotypes, yield components, grain quality, frost tolerance and the levels of expression of potential target genes in transgenic and control plants. Transgenic TaHDZipI-2 lines showed characteristic phenotypic features that included reduced growth rates, reduced biomass, early flowering, light-coloured leaves and narrowly elongated spikes. Transgenic lines produced 25-40% more seeds per spike than control plants, but with 50-60% smaller grain size. In vivo lipid imaging exposed changes in the distribution of lipids between the embryo and endosperm in transgenic seeds. Transgenic lines were significantly more tolerant to frost than control plants. Our data suggest the role of TaHDZipI-2 in controlling several key processes underlying frost tolerance, transition to flowering and spike development. PMID- 26990682 TI - BMPR1A antagonist differentially affects cartilage and bone formation during fracture healing. AB - A soluble form of BMP receptor type 1A (mBMPR1A-mFC) acts as an antagonist to endogenous BMPR1A and has been shown to increase bone mass in mice. The goal of this study was to examine the effects of mBMPR1A-mFC on secondary fracture healing. Treatment consisted of 10 mg/kg intraperitoneal injections of mBMPR1A mFC twice weekly in male C57BL/6 mice. Treatment beginning at 1, 14, and 21 days post-fracture assessed receptor function during endochondral bone formation, at the onset of secondary bone formation, and during coupled remodeling, respectively. Control animals received saline injections. mBMPR1A-mFC treatment initiated on day 1 delayed cartilage maturation in the callus and resulted in large regions of fibrous tissue. Treatment initiated on day 1 also increased the amount of mineralized tissue and up-regulated many bone-associated genes (p = 0.002) but retarded periosteal bony bridging and impaired strength and toughness at day 35 (p < 0.035). Delaying the onset of treatment to day 14 or 21 partially mitigated these effects and produced evidence of accelerated coupled remodeling. These results indicate that inhibition of the BMPR1A-mediated signaling has negative effects on secondary fracture healing that are differentially manifested at different stages of healing and within different cell populations. These effects are most pronounced during the endochondral period and appear to be mediated by selective inhibition of BMPRIA signaling within the periosteum. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2096-2105, 2016. PMID- 26990683 TI - Pulmonary aspiration under GA: a 13-year audit in a tertiary pediatric unit. AB - INTRODUCTION: Pulmonary aspiration is a known risk of general anesthesia. We aim to find out the incidence, risk factors, and outcome of pulmonary aspiration in our pediatric population. METHODS: Since 2000, all critical incidents are reported on a standardized audit form. All cases with pulmonary aspiration being reported as a critical incident were identified and their case notes traced to look at the perioperative details. RESULTS: From 2000 to 2013, a total of 102 425 pediatric cases were done in our hospital. Twenty-two cases were reported to have aspirated during anesthesia giving an incidence of 0.02% (1 in 4655). Majority (59.0%) of the children were between the ages of 3-12 and of ASA 1 (54.5%). None of them had any history of pulmonary aspiration. Of the 22 cases, 12 occurred during induction, three during maintenance, three during emergence, three during recovery, and one occurred preinduction. Twelve cases had intravenous induction while the rest received inhalational induction. The type of induction does not appear to affect the incidence of aspiration (OR 1.139 95% CI: 0.457-2.818 P = 0.76). Two cases were found to have a difficult airway during induction and 45.5% were emergency operations. Emergency surgeries put the patient at a higher risk of aspiration (OR 4.321 95% CI: 1.735-10.687 P = 0.001). No mortality was reported. Surgery was canceled for one patient, two had unplanned admissions, seven were admitted to high dependency unit or intensive care unit with two requiring postoperative ventilation. CONCLUSION: The incidence of aspiration under general anesthesia in our hospital is comparable to published reports. Our audit highlights the fact that pulmonary aspiration although rare mostly occur in healthy ASA 1 and 2 children with no prior history. Emergency surgeries put the patient at a higher risk of aspiration. They occurred usually during induction, a process which tends to be variable (in technique and duration) for pediatric patients. PMID- 26990684 TI - Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale. AB - NEW FINDINGS: What is the central question of this study? Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation <95%, in subjects with chronic heart failure with or without pulmonary arterial hypertension? What is the main finding and its importance? The presence of a patent foramen ovale contributed to resting arterial hypoxaemia only in subjects with chronic heart failure with pulmonary arterial hypertension. These data suggest that the presence of a patent foramen ovale should be considered in chronic heart failure patients with arterial hypoxaemia and pulmonary hypertension. The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxaemia at rest in subjects with chronic heart failure (CHF) have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses (Q IPAVA ) and/or patent foramen ovale (Q PFO ) could potentially contribute to arterial hypoxaemia and, with pulmonary hypertension (PH) secondary to CHF, this contribution may be exacerbated. Fifty six subjects with CHF (New York Heart Association Classes I-III), with (+) or without (-) PH [defined as peak tricuspid regurgitation velocity >=2.9 m s(-1) (CHF PH+, n = 32) and peak tricuspid regurgitation velocity <=2.8 m s(-1) (CHF PH , n = 24)], underwent arterial blood gas analysis and transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect Q IPAVA and Q PFO . Seventeen of 56 subjects with CHF (30%) had Q PFO , but only four of 56 subjects with CHF had Q IPAVA (7%), both similar to age- and sex-matched control subjects. Mean arterial oxygen saturation (SaO2) was lower in subjects with Q PFO . Only CHF PH+ subjects with Q PFO had arterial hypoxaemia (mean SaO2 <95%). Bubble scores assessed using transthoracic saline contrast echocardiography were correlated with microembolic signals detected with transcranial Doppler in subjects with Q PFO . Significant Q IPAVA was not present in either CHF PH+ or PH- subjects, suggesting that Q IPAVA is not dependent on increased pulmonary pressure and does not contribute significantly to arterial hypoxaemia in older subjects with CHF. Given that SaO2 was lower in all subjects with CHF who had Q PFO compared with those without Q PFO , a patent foramen ovale should be considered when determining potential causes of arterial hypoxaemia, because Q PFO was present in 30% of these subjects. PMID- 26990685 TI - The Huddling Programme: effects on empowerment, organisational commitment and ego resilience in clinical nurses - a randomised trial. AB - AIM AND OBJECTIVE: To identify effects of the huddling programme as a strategy for retention of clinical nurses. BACKGROUND: In Korea, new nurses leave hospitals more than experienced nurses for many reasons. Hospitals with a high nurse turnover require larger budgets and longer periods of time to train large numbers of newly recruited nurses until they can perform as well as those who have left. Furthermore, the remaining nurses have an additional workload associated with both the shortage of manpower and the need to train the incoming nurses. This means that reducing nurse turnover intention requires preventive measures that promote empowerment and organisational commitment among nurses in Korea. DESIGN: Randomised controlled trial. METHODS: This research used a pretest post-test experimental-group-control-group design to investigate the effect of the huddling programme. The participants were 49 clinical nurses working at two general hospitals with more than 500 beds that are located in D city and S city of Korea. The experimental group participated in the huddling programme that comprised a full-day retreat and after-work social networking services during January and February 2013. Self-reported questionnaires were used to assess empowerment, organisational commitment and ego-resilience. The data were analysed by descriptive analysis using the t-test. RESULTS: The mean scores for normative commitment and impact of empowerment were higher in the experimental group, but ego-resilience did not differ significantly between the two groups. CONCLUSION: The huddling program positively increased nurses' perception of organisational commitment and empowerment who participated in huddling programme. The huddling programme could be a useful strategy for improving the retention of clinical nurses. RELEVANCE TO CLINICAL PRACTICE: This study is both significant and relevant to nursing science and practice given that it demonstrated the effectiveness of an empowerment programme in increasing organisational commitment and decreasing actual turnover rates of clinical nurses. PMID- 26990686 TI - Nonparametric analysis of bivariate gap time with competing risks. AB - This article considers nonparametric methods for studying recurrent disease and death with competing risks. We first point out that comparisons based on the well known cumulative incidence function can be confounded by different prevalence rates of the competing events, and that comparisons of the conditional distribution of the survival time given the failure event type are more relevant for investigating the prognosis of different patterns of recurrence disease. We then propose nonparametric estimators for the conditional cumulative incidence function as well as the conditional bivariate cumulative incidence function for the bivariate gap times, that is, the time to disease recurrence and the residual lifetime after recurrence. To quantify the association between the two gap times in the competing risks setting, a modified Kendall's tau statistic is proposed. The proposed estimators for the conditional bivariate cumulative incidence distribution and the association measure account for the induced dependent censoring for the second gap time. Uniform consistency and weak convergence of the proposed estimators are established. Hypothesis testing procedures for two sample comparisons are discussed. Numerical simulation studies with practical sample sizes are conducted to evaluate the performance of the proposed nonparametric estimators and tests. An application to data from a pancreatic cancer study is presented to illustrate the methods developed in this article. PMID- 26990687 TI - Role of the transjugular intrahepatic portosystemic shunt in the management of severe complications of portal hypertension in idiopathic noncirrhotic portal hypertension. AB - Idiopathic noncirrhotic portal hypertension is a heterogeneous group of diseases characterized by portal hypertension in the absence of cirrhosis. The efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in this population are unknown. The charts of patients with idiopathic noncirrhotic portal hypertension undergoing TIPS in seven centers between 2000 and 2014 were retrospectively reviewed. Forty-one patients were included. Indications for TIPS were recurrent variceal bleeding (n = 25) and refractory ascites (n = 16). Patients were categorized according to the presence (n = 27) or absence (n = 14) of significant extrahepatic comorbidities. Associated conditions were hematologic, prothrombotic, neoplastic, immune, and exposure to toxins. During follow-up (mean 27 +/- 29 months), variceal rebleeding occurred in 7/25 (28%), including three with early thrombosis of the stent. Post-TIPS overt hepatic encephalopathy was present in 14 patients (34%). Eleven patients died, five due the liver disease or complications of the procedure and six because of the associated comorbidities. The procedure was complicated by hemoperitoneum in four patients (10%), which was fatal in one case. Serum creatinine (P = 0.005), ascites as indication for TIPS (P = 0.04), and the presence of significant comorbidities (P = 0.01) at the time of the procedure were associated with death. Mortality was higher in patients with significant comorbidities and creatinine >=100 MUmol/L (P < 0.001). CONCLUSION: In patients with idiopathic noncirrhotic portal hypertension who have normal kidney function or do not have severe extrahepatic conditions, TIPS is an excellent option to treat severe complications of portal hypertension. (Hepatology 2016;64:224-231). PMID- 26990688 TI - Horse anti-thymocyte globulin and eculizumab as concomitant therapeutic approach in an aplastic paroxysmal nocturnal hemoglobinuria patient: go or no-go? AB - We present the case of a 64-yr-old female paroxysmal nocturnal hemoglobinuria (PNH) patient with subsequent transition to severe aplastic anemia in whom a concomitant successful immunosuppressive therapy (horse anti-thymocyte globulin (hATG) and cyclosporin A) in addition to an ongoing long-term treatment with the terminal complement inhibitor eculizumab was initiated. No reduced ATG efficacy or severe adverse events were observed in the presence of eculizumab. In addition, the possible reoccurrence of PNH symptoms (thromboembolic events and/or intravascular hemolysis) was prevented, while T-cell depletion was similar to non eculizumab-treated patients with partial remission being evident by day 83. PMID- 26990689 TI - Estrogen and ERalpha enhanced beta-catenin degradation and suppressed its downstream target genes to block the metastatic function of HA22T hepatocellular carcinoma cells via modulating GSK-3beta and beta-TrCP expression. AB - In our previous experiments, we found beta-catenin was highly expressed in the tumor area with high invasive ability and poor prognosis. In this study, we have examined the mechanism by which ERalpha regulates beta-catenin expression as well as the metastasis ability of hepatocellular cancer HA22T cells. To identify whether the anticancer effect of estrogen and ERalpha is mediated through suppression of beta-catenin expression, we co-transfected pCMV-beta-catenin and ERalpha into HA22T cells, and determined the cell motility by wound healing, invasion, and migration assays. Results showed that estrogen and/or ERalpha inhibited beta-catenin gene expression and repressed HA22T cell motility demonstrated that similar data was observed in cells expressing the ERalpha stable clone. Moreover, we examined the protein-protein interaction between ERalpha and beta-catenin by immunostain, co-immunoprecipitation, and Western blotting. E2 enhanced the binding of ERalpha with beta-catenin and then triggered beta-catenin to bind with E3 ligase (betaTrCP) to promote beta-catenin degradation. Finally by employing systematic ChIP studies, we showed ERalpha can interact directly with the beta-catenin promoter region following E2 treatment. All our results reveal that estrogen and ERalpha blocked metastatic function of HA22T cells by modulating GSK3beta and betaTrCP expression and further enhanced beta-catenin degradation and suppressed its downstream target genes. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 519-529, 2017. PMID- 26990691 TI - In Reply. PMID- 26990690 TI - Development of nitroxide-based theranostic compounds that act both as anti inflammatory drugs and brain redox imaging probes in MRI. AB - Theranostic probes provide both therapeutic and diagnostic imaging capabilities in one molecule and show significant promise for use in magnetic resonance imaging (MRI) examinations. The present study describes for the first time the synthesis and utility of nitroxide-based contrast agents exhibiting a nonsteroidal anti-inflammatory drug effect. The target theranostic probes were prepared by connecting the carboxyl group of ibuprofen or ketoprofen to the hydroxyl group of 3-hydroxymethyl-2,2,5,5-tetramethylprrolidine-1-oxyl by a condensation reaction in the presence of dicyclohexylcarbodiimide and 4 dimethylaminopyridine in dichloromethane. MRI of mouse heads after administration of either synthesized theranostic probe indicated that the probes enter the brain by passing through the blood-brain barrier (BBB), resulting in T1 contrast enhancement in mouse brain. This enhancement persisted for the duration of the half-life of about 40 min, which is longer than that obtained by most of pyrrolidine nitroxide molecules. The therapeutic capacities of these theranostic probes were examined using a lipopolysaccharide (LPS)-induced brain inflammation model. The production of nitric oxide, an inflammation marker in septic mouse brain induced by LPS, was remarkably inhibited by the addition of either synthesized probe, indicating that they also act as anti-inflammatory drugs. The present results indicate that nitroxide-based theranostic probes act as both BBB permeable redox-sensitive contrast agents and as an anti-inflammatory drug in septic mouse brain. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990692 TI - The feminization of school hypothesis called into question among junior and high school students. AB - BACKGROUND: The feminization of school hypothesis suggests that boys underachieve in school compared to girls because school rewards feminine characteristics that are at odds with boys' masculine features. AIMS: The feminization of school hypothesis lacks empirical evidence. The aim of this study was to test this hypothesis by examining the extent to which school demands are actually associated with female more than male students. SAMPLE AND METHOD: A large sample of 1,954 students (1,115 girls and 839 boys) from grades seven, nine, 10, and 12 took part in the study. The participants were asked to rate the extent to which various characteristics valued in the school setting were exhibited by girls or boys who succeed in school. RESULTS: Three sets of characteristics related to school success emerged from the analyses: compliance, assertiveness, and effort/intelligence. Compliance and effort/intelligence were associated with the girls more than with the boys, while assertiveness was associated with the boys more than with the girls. CONCLUSION: The feminization of school hypothesis received weak support. This study discusses the limits of this hypothesis to explain boys' underachievement in comparison with girls. PMID- 26990693 TI - Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates. AB - A selection of heteroaryl fluorosulfates were readily synthesized using commercial SO2F2 gas. These substrates are highly efficient coupling partners in the Suzuki reaction. Through judicious selection of Pd catalysts the fluorosulfate functionality is differentiated from bromide and chloride; the order of reactivity being: -Br> -OSO2 F> -Cl. Exploiting this trend allowed the stepwise chemoselective synthesis of a number of polysubstituted pyridines, including the drug Etoricoxib. PMID- 26990695 TI - Gender, citizenship and dementia care: a scoping review of studies to inform policy and future research. AB - Gender is a neglected dimension in public discourse related to people with dementia. Those living with this condition are typically portrayed in policies and strategies in gender neutral terms as 'people with dementia' and 'family carers' as if gender does not matter, when clearly it does. The purpose of this scoping review was to take stock of knowledge about gender differences in relation to dementia care to inform policy and future research. The work is grounded in a feminist perspective to citizenship, as this provide a lens with which to expose and examine gendered assumptions within dementia studies. A search of four databases, including CINAHL, Web of Science, Medline and Cochrane was conducted using systematic techniques between May and July 2014. A repeat search was conducted in February 2015. We found a significant amount of valuable research concerned with gender differences in relation to dementia care published from 1990 to 2014; the majority of which lacks a feminist citizenship perspective. Moreover, a disproportionate number of studies focused solely on caregivers rather than citizens with dementia. As such, questions about gender equality are not being raised and the voices of men and women with dementia are silent. Thus we argue for increased gender-sensitivity in policy making and recommend that social scientists inject a feminist citizenship perspective into their work. PMID- 26990694 TI - Long-Term Clinical Impact of Adaptation of Initial Tacrolimus Dosing to CYP3A5 Genotype. AB - Pretransplantation adaptation of the daily dose of tacrolimus to CYP3A5 genotype is associated with improved achievement of target trough concentration (C0 ), but whether this improvement affects clinical outcomes is unknown. In the present study, we have evaluated the long-term clinical impact of the adaptation of initial tacrolimus dosing according to CYP3A5 genotype: The transplantation outcomes of the 236 kidney transplant recipients included in the Tactique study were retrospectively investigated over a period of more than 5 years. In the Tactique study, patients were randomly assigned to receive tacrolimus at either a fixed dosage or a dosage determined by their genotype, and the primary efficacy end point was the proportion of patients for whom tacrolimus C0 was within target range (10-15 ng/mL) at day 10. Our results indicate that the incidence of biopsy proven acute rejection and graft survival were similar between the control and the adapted tacrolimus dose groups, as well as between the patients who achieve the tacrolimus C0 target ranges earlier. Patients' death, cancer, cardiovascular events, and infections were also similar, and renal function did not change. We conclude that optimization of initial tacrolimus dose using pharmacogenetic testing does not improve clinical outcomes. PMID- 26990696 TI - Preconditioning methods in the management of hepatic ischemia reperfusion- induced injury: Update on molecular and future perspectives. AB - Hepatic IR (ischemia reperfusion) injury is a commonly encountered obstacle in the post-operative management of hepatic surgery. Hepatic IR occurs during 'Pringle maneuver' for reduction of blood loss or during a brief period of cold storage followed by reperfusion of liver grafts. The stress induced during hepatic IR, triggers a spectrum of cellular responses leading to the varying degrees of hepatic complications which in turn affect the post operative care. Different preconditioning methods either activate or subdue different sets of molecular signals, resulting in varied levels of protection against hepatic IR injury. Yet, there is a serious lacuna in the knowledge regarding the choice of preconditioning methods and the resulting molecular changes in order to assess the efficiency and choice of these methods correctly. This review provides an update on the various preconditioning approaches such as surgical/ischemic, antioxidant, pharmaceutical and genetic preconditioning strategies published during last six years (2009-2015). Further, we discuss the attenuation or inhibition of specific inflammatory, apoptotic and necrotic markers in the various experimental models of liver IR subjected to different preconditioning strategies. While enlisting the controversies in the ischemic preconditioning strategy, we bring out the uncertainties in the existing molecular targets and their reliability in the attenuation of hepatic IR injury. Future research studies would include the novel preconditioning strategies employ i) the targeted gene silencing of key molecular targets inducing IR, ii) hyper expression of beneficial molecular signals against IR via gene transfer techniques. The above studies would see the combination of these latest techniques with the established preconditioning strategies for better post-operative hepatic management. PMID- 26990697 TI - Consensus Statement on European Brain Research: the need to expand brain research in Europe - 2015. PMID- 26990698 TI - Acquiring surgical skills: the history of surgical teaching at the University of Sydney 1883-2014. AB - There have been at least 10 major revisions of the medical curriculum since the inauguration of the Faculty of Medicine at the University of Sydney in 1883. This study traced the evolution of the teaching of surgery at our institution by examination of the set curriculum of each period; the expectations of student knowledge in the final examination as well as examining some of the insights provided by past students of their surgical experience through their writings. In the early years, medical graduates were qualified to perform operative surgery without any further training, whereas the modern postgraduate medical curriculum provides students with the basis for further surgical training. PMID- 26990700 TI - Charge-Transfer Complex of p-Aminodiphenylamine with Maleic Anhydride: Spectroscopic, Electrochemical, and Physical Properties. AB - A new charge-transfer complex and the amide formed by the interaction between the electron donor of the p-aminodiphenylamine and the electron acceptor of maleic anhydride are investigated by spectroscopic methods. The amidation reaction is caused by proton and charge transfer between the maleic anhydride and p aminodiphenylamine molecules. The Benesi-Hildebrand equation is used to determine the formation constant, the molar extinction coefficient and the standard Gibbs free energy of the complex by using UV/Vis spectroscopy. To reveal the electronic and spectroscopic properties of these molecules, theoretical computations are performed on the structures of maleic anhydride, p-aminodiphenylamine and the conformers of their charge-transfer complex. The charge-transfer complex and amidation reaction mechanism are also confirmed by IR and NMR spectroscopy and HRMS. The nature of the maleic anhydride-p-aminodiphenylamine complex is characterized by cyclic voltammetry, thermogravimetric analysis, XRD and SEM. Solid microribbons of this complex show higher thermal stability than p aminodiphenylamine. PMID- 26990699 TI - Biomass-Derived Electrode for Next Generation Lithium-Ion Capacitors. AB - We report the fabrication of a carbon-based high energy density Li-ion hybrid electrochemical capacitor (Li-HEC) from low cost and eco-friendly materials. High surface area (2448+/-20 m(2) g(-1) ) activated carbon (AC) is derived from the environmentally threatening plant, Prosopis juliflora, and used as the positive electrode in a Li-HEC assembly. Natural graphite is employed as negative electrode and electrochemically pre-lithiated prior to the Li-HEC fabrication. The Li-HEC delivers a specific energy of 162.3 Wh kg(-1) and exhibits excellent cyclability (i.e., ~79 % of initial capacity is retained after 7000 cycles). The superior electrochemical performance of Li-HEC benefits from the tube-like unique structural features of the AC. Also, the presence of a graphitic nanocarbon network improves the ion transport, and the formed micro- and meso-porous network acts as reservoir for the accommodation of charge carriers. PMID- 26990701 TI - One tube with eight antibodies for 14-part bone marrow leukocyte differential using flow cytometry. AB - BACKGROUND: Bone marrow analysis by flow cytometry is part of the routine diagnosis of hematological disorders in medical laboratories. Differential leukocyte count and identification of abnormal cell subsets is currently performed through morphological examination on bone marrow smears by skilled cytologists. In this work, we propose a single 8-color tube for providing equivalent information, using flow cytometry. METHODS: 99 bone marrow samples were classified into 2 groups, (i) 51 samples, obtained from either healthy donors (n = 4) or patients with various diseases at diagnosis or during remission that did not present a hematological malignancy (n = 47), and (ii) 48 pathological samples with quantitative and/or qualitative abnormalities. A panel of eight antibodies-CD3-FITC/CD10-PE/CD38-PerCP-Cy5.5/CD19-PECy7/CD36-APC/CD16 APC-H7/CD34-BV421/CD45-V500-was tested to identify the main cell subsets at different stages of maturation using a FACSCanto-II analyzer. RESULTS: We first proposed a strategy of sequential gating leading to the identification of 14 leukocyte subsets, that is, erythroblasts, monocytes, B-lymphoid cells from hematogones to plasma-cells (5 subsets), T- and NK-cells, polymorphonuclear cells (neutrophils, eosinophils, and basophils), myeloblasts and other immature granular cells. This approach was validated by comparing flow cytometry and microscopic morphological examination, both in cases of normal and abnormal samples. Interestingly, cell identification, and numeration by flow cytometry was easy to perform and highly reproducible. CONCLUSION: A very simple, rapid, and reproducible flow cytometric approach, using a combination of eight antibodies allows determination of the cellular composition of bone marrow with high precision. (c) 2016 International Clinical Cytometry Society. PMID- 26990702 TI - Assessment of Polygonum capitatum Buch.-Ham. ex D.Don by metabolomics based on gas chromatography with mass spectrometry. AB - Polygonum capitatum is widely used in southwest China. It has considerable therapeutic efficacy for urinary tract infections. P. capitatum contains multiple components and quality assessment can be achieved by means of metabolic fingerprinting. In this paper, a new strategy for P. capitatum quality determination was developed. Eleven batches of P. capitatum were collected from five geographical areas in China including a standard batch regulated by Good Agriculture Practice. Gas chromatography with mass spectrometry was used to generate fingerprints from triplicate extractions to each batch (n = 33). Hierarchical clustering analysis was applied to assess similarities among the ten batches to the standard batches. Orthogonal projection to latent structures discriminate analysis, cross-validated with permutation tests, was performed to investigate discriminating metabolites. Results demonstrated that the overall evaluation hierarchical clustering analysis clustered two batches with distance > 3. Orthogonal projection to latent structures discriminate analysis (R(2) Y (cum) = 0.997, Q(2) (cum) = 0.97, CV-ANOVA = 8.48 * 10(-11) ) indicated that several sugars contributed to batch classification. This method is a rational approach that can classify against a regulated plant standard and distinguishes samples from different origins or processing time in a holistic manner and metabolites driving any differences can be easily identified. PMID- 26990703 TI - Generation and Reaction of Carbamoyl Anions in Flow: Applications in the Three Component Synthesis of Functionalized alpha-Ketoamides. AB - Using a flow microreactor system, carbamoyllithium compounds were successfully generated and used for reactions with electrophiles to give various amides, including alpha-ketoamides. The present method could be applied to the three component synthesis of functionalized alpha-ketoamides using a carbamoyllithium compound, methyl chloroformate, and a functionalized organolithium reagent. PMID- 26990704 TI - Wearable monitors for patients following discharge from an intensive care unit: practical lessons learnt from an observational study. AB - AIMS: To identify the practical challenges encountered when using wearable monitors for patients discharged from the intensive care unit. BACKGROUND: Patients discharged from intensive care units are a high-risk group that might benefit from continuing observation using 'wearable' monitors to enable faster identification of physiological deterioration and facilitate timely clinical action. This area of technological innovation is of key interest to nurses who manage this group of patients. DESIGN: A prospective observational study. METHODS: An observational study conducted in 2013-2014 used wearable monitors to record continuous observations for patients discharged from an intensive care unit to develop a predictive model of patients likely to deteriorate. Screening data for study eligibility and case report form data to assess monitor tolerance and comfort were collected daily and analysed using Microsoft Access. RESULTS/FINDINGS: Patients (n = 2704) were discharged from an intensive care unit during the study, 208 consented to wearing the monitor. Of the 192 included in analysis, 130 (67.7%) removed the monitor before the trial finished. Reasons cited for removal included 'discomfort and irritation' 61 (31.8%) and 'feeling too unwell' 8 (4.2%). Five hundred seventeen patients were screened following adaption of the wearable monitor. Despite design changes, 56 (10.8%) patients were unable to wear monitors for reasons related to their anatomy or condition. Of 124 patients, 65 patients (52.4%) who were approached refused participation. CONCLUSION: Work is needed to understand wireless monitor comfort and design for acutely unwell patients. Product design needs to develop further, so patients are catered for in flexibility of monitor placement and improved comfort for long term wear. PMID- 26990705 TI - Optimization of Fracture Resistance and Stiffness of Heat-Polymerized High Impact Acrylic Resin with Localized E-Glass FiBER FORCE(r) Reinforcement at Different Stress Points. AB - PURPOSE: Dentures are subject to fracture through flexural stresses during masticatory function. Distribution of stresses under flexural loading varies from compressive to tensile stress along the thickness of the denture cross section. The goal of this investigation was to evaluate the effect of reinforcing compressive, tensile, and no stress regions of flexurally loaded rectangular bars of heat-cured denture base acrylic resin reinforced with tough E-Glass FiBER FORCE (GFF) on their fracture resistance under flexural loading. MATERIALS AND METHODS: Forty rectangular specimens (65 mm long * 10 mm wide * 2.5 mm thick) were prepared and divided into four groups (n = 10). Group FN had no fiber reinforcement, group FM had fiber in the middle at the no-stress neutral axis, group FC had fiber close to the surface on the compressive stress side, and group FT had the fiber close to the surface on the tensile stress side. The effect of GFF reinforcement on flexural strength (FS), flexural toughness (TG), and flexural modulus of elasticity (MOE) was evaluated. RESULTS: The mean and (SD) of the FS, TG, and MOE varied as follows. FS (MPa): group FN: 91.49 (7.88); group FM: 102.83 (13.5); group FC: 107.68 (11.21); group FT: 141.46 (14.77). TG (mJ/mm3 ): group FN: 0.171 (0.026); group FM: 0.236 (0.033); group FC: 0.156 (0.032); group FT: 0.347 (0.010). MOE (MPa): group FN: 2682 (761); group FM: 2601 (417); group FC: 4188 (1012); group FT: 4215 (674). Statistical analysis showed that reinforcement on the tensile side of the neutral axis yielded improvement in all properties evaluated. CONCLUSIONS: Placement of the GFF close to the tensile stress side surface of the bar increased the resistance to elastic deformation (i.e., higher MOE or stiffness) and the stress level needed for flexural fracture (i.e., higher FS). In addition, more energy was absorbed by reinforced specimens before fracture occurred (i.e., higher toughness). Localized reinforcement targeting tensile stress centers is thus a practical way to improve clinical durability of dentures against intra- and extraoral fracture. PMID- 26990707 TI - Effects of apple pomace-mixed silage on growth performance and meat quality in finishing pigs. AB - We measured the growth performance and meat quality of 10 crossbred (Yorkshire * Duroc * Landrace) neutered male pigs to evaluate the effects of apple pomace mixed silage (APMS). The pigs were divided into two groups and were respectively fed the control feed and the AMPS ad libitum during the experiment. No difference was found in the finished body weight, average daily gain, carcass weight, back fat thickness or dressing ratio between the control and the AMPS treatments, but average dairy feed intake (dry matter) was significantly lower and feed efficiency was significantly higher using the APMS treatment (P < 0.05). With regard to meat quality, the APMS increased the moisture content but decreased the water holding capacity (P < 0.05) compared with the control treatment. Furthermore, the APMS affected the fatty acid composition of the back fat by increasing linoleic acid (C18:2n6), linolenic acid (C18:3) and arachidic acid (C20:0) levels, while decreasing palmitic acid (C16:0), palmitoleic acid (C16:1) and heptadecenoic acid (C17:1) levels, compared with the control treatment. These results indicate that feeding fermented apple pomace to finishing pigs increases the feed efficiency and affects the meat quality and fatty acid composition of back fat. PMID- 26990706 TI - Intra-individual gait pattern variability in specific situations: Implications for forensic gait analysis. AB - In this study, inter- and intra-individual gait pattern differences are examined in various gait situations by means of phase diagrams of the extremity angles (cyclograms). 8 test subjects walked along a walking distance of 6m under different conditions three times each: barefoot, wearing sneakers, wearing combat boots, after muscular fatigue, and wearing a full-face motorcycle helmet restricting vision. The joint angles of foot, knee, and hip were recorded in the sagittal plane. The coupling of movements was represented by time-adjusted cyclograms, and the inter- and intra-individual differences were captured by calculating the similarity between different gait patterns. Gait pattern variability was often greater between the defined test situations than between the individual test subjects. The results have been interpreted considering neurophysiological regulation mechanisms. Footwear, masking, and fatigue were interpreted as disturbance parameters, each being a cause for gait pattern variability and complicating the inference of identity of persons in video recordings. PMID- 26990708 TI - Elucidation of Adsorbate Structures and Interactions on Bronsted Acid Sites in H ZSM-5 by Synchrotron X-ray Powder Diffraction. AB - Microporous H-ZSM-5 containing one Bronsted acid site per asymmetric unit is deliberately chosen to host pyridine, methanol, and ammonia as guest molecules. By using new-generation in situ synchrotron X-ray powder diffraction combined with Rietveld refinement, the slight but significant alteration in scattering parameters of framework atoms modified by the guest molecules enables the user to elucidate their adsorption geometries and interactions with the Bronsted acid sites in H-ZSM-5 in terms of atomic distances and angles within experimental errors. The conclusion, although demonstrated in the H-ZSM-5, is expected to be transferable to other zeolites. This approach provides a stepping stone towards the rational engineering of molecular interaction(s) with acid sites in zeolitic catalysis. PMID- 26990710 TI - Medulloblastoma with extensive nodularity: a tumour exclusively of infancy? PMID- 26990709 TI - Comparison of clinical explants and accelerated hydrolytic aging to improve biostability assessment of silicone-based polyurethanes. AB - Although silicone-based polyurethanes have demonstrated increased oxidative stability, there have been conflicting reports of the long-term hydrolytic stability of OptimTM and PurSil((r)) 35 based on recent temperature-accelerated hydrolysis studies. The goal of the current study was to identify in vitro-in vivo correlations to determine the relevance of this accelerated in vitro model for predicting clinical outcomes. Temperature-accelerated hydrolytic aging of three commonly used cardiac lead insulation materials, OptimTM, ElasthaneTM 55D, ElasthaneTM 80A, and a related silicone-polyurethane, PurSil((r)) 35, was performed. After 1 year at 85 degrees C, similar losses in Mn and Mz were observed for the poly(ether urethanes), but an increase in Mz loss as compared to Mn loss was observed for the silicone-based polyurethanes. A similar trend of increased Mz loss as compared to Mn loss was observed in explanted OptimTM leads after 2-3 years; however, no statistically significant Mn loss was detected between 2-3 and 7-8 years of implantation. Given this preferential loss of high molecular weight chains, it was hypothesized that the observed differences between the polyurethanes were due to allophanate dissociation rather than backbone chain scission. Following full dissociation of the small percentage of allophanates in vivo, the observed molecular weight stability and proven clinical performance of OptimTM was attributed to the well-documented stability of the urethane bond under physiological conditions. This allophanate dissociation reaction is incompatible with the first order mechanism proposed in previous temperature-accelerated hydrolysis studies and may be the reason for the model's inaccurate prediction of significant and progressive molecular weight loss in vivo. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1805 1816, 2016. PMID- 26990711 TI - Atomic Resolution in Situ Imaging of a Double-Bilayer Multistep Growth Mode in Gallium Nitride Nanowires. AB - We study the growth of GaN nanowires from liquid Au-Ga catalysts using environmental transmission electron microscopy. GaN wires grow in either ?1120? or ?1100? directions, by the addition of {1100} double bilayers via step flow with multiple steps. Step-train growth is not typically seen with liquid catalysts, and we suggest that it results from low step mobility related to the unusual double-height step structure. The results here illustrate the surprising dynamics of catalytic GaN wire growth at the nanoscale and highlight striking differences between the growth of GaN and other III-V semiconductor nanowires. PMID- 26990712 TI - Preoperative Planning in Primary Total Knee Arthroplasty. AB - Preoperative planning is of paramount importance in primary total knee arthroplasty. A thorough preoperative analysis helps the surgeon envision the operation, anticipate any potential issues, and minimize the risk of premature implant failure. Obtaining a thorough history is critical for appropriate patient selection. The physical examination should evaluate the integrity of the soft tissues, the neurovascular status, range of motion, limb deformity, and the status of the collateral ligaments to help determine the soft-tissue balancing and constraint strategy required. Standard radiographs, with a known magnification, should be obtained for preoperative total knee arthroplasty templating. Routine standing AP, lateral, and skyline radiographs of the knee can help the surgeon plan the bone cuts and tibial slope as well as the implant size and position at the time of surgery. In certain circumstances, such as severe coronal deformities, bone deficiencies, and/or extra-articular deformities, additional measures are frequently necessary to successfully reconstruct the knee. Constrained implants, metal augments, and bone graft must be part of the surgeon's armamentarium. PMID- 26990713 TI - Greater Trochanteric Pain Syndrome. AB - Patients who have lateral hip pain historically have been diagnosed with trochanteric bursitis and treated with nonsteroidal anti-inflammatory medications, corticosteroid injections, and physical therapy. Although this strategy is effective for most patients, a substantial number of patients continue to have pain and functional limitations. Over the past decade, our understanding of disorders occurring in the peritrochanteric space has increased dramatically. Greater trochanteric pain syndrome encompasses trochanteric bursitis, external coxa saltans (ie, snapping hip), and abductor tendinopathy. A thorough understanding of the anatomy, examination findings, and imaging characteristics aids the clinician in treating these patients. Open and endoscopic treatment options are available for use when nonsurgical treatment is unsuccessful. PMID- 26990714 TI - Role of the Subchondral Bone in Articular Cartilage Degeneration and Repair. PMID- 26990715 TI - Peptide-Decorated Dendrimers and Their Bioapplications. AB - Peptide-decorated dendrimers (PDDs) are a class of spherical, regular, branched polymers that are modified by peptides covalently attached to their surface. PDDs have been used as protein mimetics, novel biomaterials, and in a wide range of biomedical applications. Since their design and development in the late eighties, poly-l-lysine has been a preferred core structure for PDDs. However, numerous recent innovations in polymer synthesis and ligation chemistry have re-energized the field and led to the emergence of well-defined peptide dendrimers with more diverse core structures and functions. This Minireview highlights the development of PDDs driven by significantly improved ligation chemistry incorporating structurally well-defined peptides and the emerging use of PDDs in imaging and drug development. PMID- 26990716 TI - The implementation of a transanal endoscopic microsurgery programme: initial experience with surgical performance. AB - AIM: Despite transanal endoscopic microsurgery (TEM) being used for over 30 years, there has been slow adoption of this modality in many centres. There remains a paucity of research regarding the learning curve and early performance of surgeons who begin to offer TEM. We sought to determine predictors of longer rates of tumour excision and improvements in operative time in a newly established TEM programme. METHOD: All patients who underwent TEM at the Ottawa Hospital, Ottawa, Canada, between October 2009 and September 2014 were included. Data were abstracted through a retrospective chart review. The average rate of lesion excision (ARE) was calculated to standardize the operation time by size of the pathological specimen (min/cm3 ), representing a measure of surgical efficiency. Surgical efficiency was plotted using restricted cubic splines. Predictors of higher ARE were determined using multivariable regression. RESULTS: During the study period 108 patients underwent TEM. ARE was available for 95 patients of mean age 67.2 years. The mean ARE was 18.6 min/cm3 . On adjusting for important covariates, the ARE improved with each additional case until 16 cases were completed. Significant predictors of higher ARE on multivariable analysis were age < 50 years, experience of fewer than five cases, and carcinoid/gastrointestinal stromal tumour or scar histology. CONCLUSION: Operative efficiency appears to improve as surgeons completed 16 TEM cases. We have identified important factors that result in longer operating time. The study has important implications with regard to surgical training and operative planning for new TEM programmes. PMID- 26990718 TI - Choosing an Important Project: The First Stage to Getting Research Published. PMID- 26990717 TI - Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: current state of the art. AB - Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant recipients. The significant clinical impact of HCMV infection and progression to HCMV disease among allogeneic hematopoietic stem cell transplant recipients has been reduced by prophylactic, preemptive, and curative treatments using ganciclovir, valganciclovir, foscarnet, and cidofovir. Resistance to (val)ganciclovir results from mutations localized in HCMV UL97 gene (encoding the pUL97 phosphotransferase), UL54 gene (encoding the pUL54 DNA polymerase), or both genes, whereas foscarnet and cidofovir resistance results from mutations localized within UL54 gene only. This review is focused on HCMV antiviral drug resistance, including the functions of target genes of antivirals, the mechanisms of antiviral resistance, the different mutations in pUL97 and pUL54 that have been identified in either clinical isolates or laboratory strains, and their impact on HCMV susceptibility to antiviral drugs. It emphasizes the importance of proving that observed genetic changes confer resistance so they can be distinguished from polymorphisms. Because of the emergence of HCMV resistance to currently available drugs, novel drugs are urgently needed for the therapeutic management of HCMV-resistant infections in hematopoietic stem cell transplant patients. PMID- 26990719 TI - Influence of Field Position on Rugby League Players Requiring Shoulder Reconstruction. AB - A consecutive series of patients sustaining their index anterior instability while playing Rugby League and requiring shoulder reconstruction was retrospectively reviewed and evaluated. The details of their on-field position and hand dominance at time of injury, the side of injury, and mechanism of injury were collated and statistically analyzed. A total of 173 Bankart repairs were performed on 132 patients, and 102 players had one injury while 30 had 2 or more injuries. Players are more likely to injure their non-dominant side (P=0.009) in the first-time injury. Whereas second and subsequent injuries were not associated with a particular side (P=0.81). Applying a Bonferroni correction to the chi squared goodness-of-fit test of position at time of injury revealed players on the wing had a significantly lower frequency of injury (P<0.001), whereas the full back had a significantly higher frequency of injury (P<0.001). 30 players sustained 69 re-dislocations with the lock and fullback positions incurring significantly more re-injuries and the wing position fewer re-injuries than expected (P<0.006). Understanding which player positions on the rugby league field are more likely to sustain an anterior instability will assist medical and support staff to optimize the pre-season conditioning and post surgical rehabilitation of players. PMID- 26990720 TI - Enhancement of Polyethylene Terephthalate Artificial Ligament Graft Osseointegration using a Periosteum Patch in a Goat Model. AB - The purpose of this study is to investigate whether a periosteum patch could enhance polyethylene terephthalate (PET) artificial ligament graft osseointegration in a bone tunnel. 12 female goats underwent ACL reconstruction with a PET artificial ligament graft in the right knees. Right knees in 6 goats were reconstructed with periosteum patch-enveloped PET grafts (Periosteum group) in the tibia bone tunnel, whereas the other 6 goats had no periosteum patch and served as the Control group. All the goats were sacrificed at 12 months after surgery. 3 tibial-graft complex samples in each group were harvested consecutively for microcomputed tomography (micro-CT) scan, magnetic resonance imaging (MRI) scan and histological evaluation. The other 3 tibial-graft complex samples in each group were harvested for biomechanical testing. The mean pull-out load of the Periosteum group (208+/-25 N) at 12 months was significantly higher than that of the Control group (107+/-13 N) (p=0.0044). According to the micro-CT scan, more new bone formation was observed at the graft-bone interface in the Periosteum group compared with the Control group. Furthermore, MRI showed that the Periosteum group appeared to have a better graft osseointegration within the bone tunnel compared with the Control group. Histologically, application of a periosteum patch induced more new bone and Sharpey's fiber formation between the graft and bone tunnel compared with the controls. The study has shown that periosteum enveloping of the PET artificial ligament has a positive effect in the induction of artificial ligament osseointegration within the bone tunnel. PMID- 26990721 TI - Influence of Skeletal Maturity on Size, Function and Sport-specific Technical Skills in Youth Soccer Players. AB - This study compared variation in size, function and sport-specific technical skills of youth soccer players associated with differences in biological maturity status. 60 male soccer players of under-14 (U14) and under-17 (U17) categories were submitted to anthropometric and body composition measurements as well as motor and soccer-specific technical skill tests. Skeletal maturity was determined by skeletal age. Athletes of both categories were classified as early, on-time or late-maturing, according to the difference between chronological age and skeletal age. Body mass and height were lower in the late athletes, independent of category (P<0.01). Differences in adiposity were found only between athletes of the U14 (late=60 years who do not have weakened immune systems. It is unclear how the risk of HZ varies according to age and disease conditions in younger patients with autoimmune or inflammatory (AI) diseases. This study was undertaken to evaluate the age-stratified incidence of HZ in patients with AI diseases as compared to older adults for whom the HZ vaccine is currently recommended by the US Centers for Disease Control and Prevention. METHODS: Using linked data obtained from patients who were insured by US commercial and government health care plans during the period 2007-2010, 7 cohorts of patients with AI diseases were assembled: systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), ankylosing spondylitis (AS), and gout. Two comparator cohorts were also assembled as controls: adult patients with diabetes and adult subjects without AI diseases or diabetic conditions. HZ was identified using diagnostic codes. Age-specific incidence rates (IRs) of HZ were calculated and compared to the IRs of HZ in control subjects ages 61-70 years who were without AI diseases or diabetic conditions. RESULTS: After review of the linked data, the following number of enrollment periods were identified: 8,395 for patients with SLE, 7,916 for patients with IBD, 50,646 for patients with RA, 2,629 for patients with PsA, 4,299 for patients with PsO, 1,019 for patients with AS, 58,934 for patients with gout, 214,631 for control patients with diabetes, and 330,727 for control subjects without AI diseases and diabetic conditions. The respective highest and lowest IRs of HZ during the study were 19.9 per 1,000 person-years in the SLE cohort and 6.8 per 1,000 person-years in the gout cohort, as compared to an IR of 5.3 per 1,000 person-years in control subjects without AI diseases or diabetic conditions. The age-specific IRs of HZ in patients with RA and those with SLE ages >=40 years were 1.5-2 times greater than those observed in older healthy adults (IR 8.5 per 1,000 person-years), for whom the vaccine is currently recommended. CONCLUSION: SLE, IBD, and RA are AI diseases associated with a higher risk of HZ compared to that in older adults for whom vaccination is currently recommended, suggesting that individuals with these conditions who are as young as age 40 years could potentially benefit from the HZ vaccine. PMID- 26990733 TI - Determination of six polyether antibiotic residues in foods of animal origin by solid phase extraction combined with liquid chromatography-tandem mass spectrometry. AB - A new method using solid phase extraction (SPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of six polyether antibiotics, including lasalocid, salinomycin, monensin, narasin, madubamycin and nigericin residues, in foods of animal origin. The samples were extracted with acetonitrile and purified by ENVI-Carb SPE columns after comparing the impurity effect and maneuverability of several SPE cartridges. Subsequently, the analytes were separated on a Hypersil Gold column (2.1*150mm, 5MUm) and analyzed by MS/MS detection. The limit of quantization (LOQ) for milk and chicken was 0.4MUg/kg, and for chicken livers and eggs, it was 1MUg/kg. The linearity was satisfactory with a correlation coefficient of >0.9995 at concentrations ranging from 2 to 100MUg/L. The average recoveries of the analytes fortified at three levels ranged from 68.2 to 114.3%, and the relative standard deviations ranged from 4.5 to 12.1%. The method was suitable for quantitative analysis and confirmation of polyether antibiotic residues in foods of animal origin. PMID- 26990734 TI - Comparative analysis of bioactive N-alkylamides produced by tissue culture raised versus field plantlets of Spilanthes ciliata using LC-Q-TOF (HRMS). AB - Spilanthes ciliata (S. ciliata) is a perennial herb of global importance owing to its luscious source of bioactive fatty acid derived amides known as N alkylamides. It finds application in skin creams, mouth gels and toothpastes. Despite multifaceted applications, a major limitation associated for its commercial application is the scarcity of contamination free plant source, fluctuations in active metabolites due to variation in extraction procedures, and lack of rapid qualitative method for alkylamide profiling. In the current work, attempts were made to 1) optimize conditions for mass propagation of contamination free plants of S. ciliata by tissue culture using leaf discs as explants, 2) establish an optimum extraction ratio of plant/solvent (w/v) for maximum elution of alkylamides and 3) develop a rapid method for qualitative estimation of alkylamide from in vitro raised plants in comparison with that of the field grown counterpart by using LC-Q-TOF (HRMS). To the best of our knowledge, this is the first qualitative report on alkylamide profile of micropropagated whole plant of Spilanthes. The correlation pattern reported in this study may form the basis for using tissue culture raised plantlets of S. ciliata as potential source of bioactive alkylamides on industrial scale. PMID- 26990735 TI - UFLC-MS/MS analysis of four tanshinone components in Salvia miltiorrhizae after ultrasound-assisted extraction. AB - A sensitive and rapid ultra-fast liquid chromatography with tandem mass spectrometry (UFLC-MS/MS) method was developed for simultaneous qualitative and quantitative of four characteristic tanshione components including tanshinone IIA, cryptotanshinone, tanshinone I and dihydrotanshinone I in Salvia miltiorrhizae after ultrasound-assisted extraction. By using a C18 column, the four analytes were separated by gradient elution with acetonitrile and water both containing 0.1% formic acid at the flow rate of 0.3mL/min. Multiple-reaction monitoring (MRM) was used for quantification, and an information-dependent acquisition (IDA) method was used to trigger enhanced product ion scans (EPI) for supplementary characteristic identification for qualitative research. Calibration curves showed good linearities with correlation coefficients (r) higher than 0.9990. The method showed high sensitivity with limits of detection (LODs) and quantification (LOQs) less than 0.0002ng/mL and 0.0008ng/mL, respectively, as well as good precision and reproducibility. Mean recoveries for four analytes ranged from 92.5% to 106.2% with relative standard deviations (RSDs) lower than 14.59%. Real application of the developed method in 32 batches of S. miltiorrhizae samples demonstrated that the total contents of four analytes in all samples were in the range of 2.258-52.342mg/g. Ultrasound-assisted extraction technique took a small amount of sample and low time but giving high extraction efficiency. Combining with UFLC-MS/MS method in MRM-IDA-EPI mode, more components in other complicated matrices can be simultaneously analyzed for qualitation and quantitation in one run. PMID- 26990736 TI - Multi-residue analysis of 26 organochlorine pesticides in Alpinia oxyphylla by GC ECD after solid phase extraction and acid cleanup. AB - A simple and effective multi-residue method was developed and validated for the analysis of 26 organochlorine pesticide residues in Alpinia oxyphylla by a gas chromatography with an electron capture detector (GC-ECD). The target pesticides were extracted by sonication and cleaned up with florisil solid phase extraction and sulphuric acid. Some crucial parameters, including extraction solvent and time, sorbent type, elute solvent and concentration of sulphuric acid were optimized to improve the performance of sample preparation procedure. The optimized method gave high sensitivity with detection limit ranging from 0.1 to 2.0MUg/kg. Matrix-matched calibration was employed for the quantification, and a wide linear range (from 1.0 to 1000MUg/kg) with r(2) values ranging from 0.9971 to 0.9998 was obtained. For the majority of the tested pesticides, the average recoveries were in acceptable range (between 70% and 110%) with relative standard deviation values below 15.0%. Matrix effect was evaluated for target compounds through the study of ratio of peak area obtained in the solvent and blank matrix. The proposed method was applied to simultaneously analyze 26 pesticides in 55 batches of Alpinia oxyphylla samples. 3 samples were found to be positive with four pesticides (alpha-BHC, quintozene, trans-chlordane and op'-DDD), which were confirmed by gas chromatography-mass spectrometry (GC-MS) in selective ion monitoring (SIM) mode. PMID- 26990737 TI - Separation of catechins and O-methylated (-)-epigallocatechin gallate using polyamide thin-layer chromatography. AB - Thin-layer chromatography (TLC) method for the separation and quantitative determination of seven related compounds: (+)-catechin (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), (-)-epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me) and (-) epigallocatechin- 3-O-(4-O-methyl) gallate (EGCG4"Me) has been developed. The above-mentioned seven compounds have been resolved using polyamide TLC plates using a double-development with methanol followed by acetone/acetic acid (2:1, v/v). In addition, separation of the phenolic acids namely gallic acid, chlorogenic acid, and caffeic acid was achieved using the same solvent system. The applicability of the method was checked by screening of extracts of green, black, oolong, white tea and tea cultivars leaves. PMID- 26990738 TI - Microdialysis combined with liquid chromatography-tandem mass spectrometry for the determination of nimodipine in the guinea pig hippocampus. AB - Nimodipine is a dihydropyridine calcium-channel blocker that has been recently shown to be effective on the function of central nervous system. It has been reported that treatment against deficits of learning and memory in animals and human by maintain the calcium homeostasis in hippocampus with nimodipine may be promising therapeutic strategies. A rapid and sensitive liquid chromatography tandem mass spectrometric method was developed to determination the nimodipine in hippocampus using microdialysis technique. The separation was accomplished on an Agilent Zorbax SB-C18 column (100mm*2.1mm ID, 3.5MUm) with the mobile phase composed of methanol-water (80:20, v/v) containing 0.2% formic acid at a flow rate of 0.2ml/min. Multiple reaction monitoring of the precursor-product ion transitions 419->343 for nimodipine and 361->315 nitrendipine (IS) was used for quantitation. The method was sensitive with a lower limit of quantitation (LLOQ) of 0.2ng/ml for nimodipine, with good linearity in the range of 0.2-20ng/ml. All the validation data, such as accuracy, precision, intra- and inter-day repeatability and stability were within the required limits. The method was successfully applied to p harmacokinetic study of the nimodipine in the guinea pig hippocampus. PMID- 26990739 TI - Comparison of two extraction methods for the determination of 135 pesticides in Corydalis Rhizoma, Chuanxiong Rhizoma and Angelicae Sinensis Radix by liquid chromatography-triple quadrupole-mass spectrometry. Application to the roots and rhizomes of Chinese herbal medicines. AB - In this study, two simple pretreatment methods were comprehensively evaluated for the determination of 135 pesticide residues in roots and rhizomes of Chinese herbal medicines (CHMs). The studied methodologies are (a) solid-phase extraction (SPE) and (b) Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS). For SPE, extraction solvents, SPE cartridges and types and volume of eluent were accessed and optimized. For QuEChERS, different versions, acetic acid concentration and dispersive solid-phase extraction (dSPE) sorbent materials were tested. SPE and QuEChERS were estimated in recovery range, the number of pesticides that were recovered ranging from 90% to 110% and expenses in Corydalis Rhizoma, Chuanxiong Rhizoma and Angelicae Sinensis Radix. QuEChERS method showed better performance than SPE. The method showed good linearity over the range assayed 0.9986-0.9999 (1-80ng/mL for 124 pesticides, 1-50ng/mL for 10 pesticides, 1-20ng/mL for satisfar). The matrix effect was compensated by matrix-based calibration curves with internal standard. The average recoveries of all pesticides were ranging from 70% to 120% at three levels of 10, 50 and 100ng/g with relative standard deviations less than 20%. The limits of quantification of the 135 pesticides in three matrices were 1-5ng/g, which were below the maximum residue levels (MRLs) established by the European Union. The verified QuEChERS method was successfully applied to the analysis of 65 actual samples from eight different types of roots and rhizomes of CHMs. Angelicae Sinensis Radix was the most susceptible to pesticides among these samples, and the most frequently detected pesticide was carbendazim with levels below MRLs. Metalaxyl, phorate, atrazine, diniconazole, coumaphos and paclobutrazol were also detected in some samples. PMID- 26990740 TI - Is it all in the reward? Peers influence risk-taking behaviour in young adulthood. AB - The presence of peers is suggested to increase risk-taking behaviour by heightening response to reward. The current study investigated this using a computerized financial risk-taking task which was performed twice by a group of young adults (n = 201, median age 19.8 years): once alone and once while in the presence of two peers. An overall increase in risk-taking was observed when with peers compared to when alone (CHANGE). CHANGE was positively associated with self reported levels of reward responsiveness and fun seeking while older age and lack of perseverance were associated with reduced CHANGE. The association between risk taking when with peers and both resistance to the influence of peers and age was indirect through reward responsiveness. Reward responsiveness was positively associated with impulsiveness. Only in those who showed a peer-related decrease in risk-taking (1/3 of participants), risk-taking in the presence of peers was associated with increased impulsiveness. The current findings suggest an important role for reward responsiveness in risk-taking behaviour and demonstrate the influence of peers. Increased understanding of these processes has direct implications for prevention and intervention efforts. Placing risk-taking behaviour within varying (social) contexts with an eye for differences in personality, development, and emotions provides ample scope for future research. PMID- 26990741 TI - Boston Type 1 Keratoprosthesis for Gelatinous Drop-Like Corneal Dystrophy. AB - PURPOSE: To report the outcomes of Boston type 1 keratoprosthesis in the management of advanced gelatinous drop-like corneal dystrophy (GDLD). METHODS: A retrospective, noncomparative, interventional case series was conducted at Ramathibodi Hospital, Bangkok, Thailand. Four eyes of three siblings with molecularly and histologically confirmed GDLD from a Thai family underwent an uneventful Boston type 1 keratoprosthesis implantation for visual rehabilitation. Clinical data were obtained from a review of the medical records. Visual acuity, device retention, and postoperative complications were the main outcome measures. The follow-up ranged from 8 to 96 months. RESULTS: One eye received keratoprosthesis surgery as a primary penetrating procedure. The other three eyes had the surgery as a secondary procedure after graft failure. Best-corrected visual acuity was favorably improved from counting fingers to 20/25 in two eyes, from hand movement to 20/20 in one eye, and from hand movement to counting fingers at 2 feet in one eye caused by severe amblyopia. The improved vision was maintained for 8 months to 6.2 years after surgery. Postoperative complications included disease recurrence in the donor graft (N = 3), manageable retroprosthetic membrane (N = 3), intraocular pressure elevation responded to antiglaucoma drugs (N = 2), and Pseudomonas keratitis with severe corneal melting requiring device removal (N = 1). All of our patients failed to have a comfortably well-fitting contact lens after surgery. CONCLUSIONS: Boston type 1 keratoprosthesis could be considered as a reasonable option in the management of advanced GDLD. However, patients remain at risk for sight-threatening postoperative complications as long as the keratoprosthesis is retained. The use of Boston keratoprosthesis implantation needed to be individualized on a case-by case basis. PMID- 26990742 TI - Integration of VEGF and alpha-SMA Expression Improves the Prediction Accuracy of Fibrosis in Chronic Hepatitis C Liver Biopsy. AB - INTRODUCTION: The progression of fibrosis in chronic hepatitis C (CHC) is a multifactorial process. The high adverse effects and the cost of standard health care increase the demand to discover new predictors for the progression of fibrosis in CHC patients. Our study aims to establish the relation between the angiogenic marker [vascular endothelial growth factor (VEGF)] and activated hepatic stellate cells (HSCs) represented by the expression of alpha-smooth muscle actin (alpha-SMA) and whether these 2 markers can be used as predictors for the progression of fibrosis in patients with CHC. MATERIALS AND METHODS: Histopathologic and immunohistochemical analyses were used for examining the morphology and the expression of VEGF and alpha-SMA in 60 CHC biopsies procured from CHC patients. Multivariate analysis was used to correlate the protein expression with staging and grading of liver fibrosis. Cutoff values of alpha-SMA and VEGF were determined by the receiver operating characteristics curve. RESULTS: There was a positive correlation between VEGF and HSCs expressing alpha SMA (rho=0.287, P=0.026) and both factors were correlated with the stage of fibrosis (P<0.001). Using the receiver operating characteristics curve, both VEGF (area under the curve=0.71, P<0.006) and alpha-SMA (area under the curve=0.82, P<0.001) were positive predictors for moderate and severe fibrosis. CONCLUSIONS: This study demonstrates the relation between VEGF expression and the activated HSCs denoted by the expression of alpha-SMA in CHC biopsies and together can be used as a predictor for the progression of fibrosis. PMID- 26990743 TI - Cytokeratin 17 Expression is Associated With Poor Prognosis in Gallbladder Adenocarcinoma. AB - Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, is a poor prognostic marker for cancers of organs such as the stomach, ovary, and breast as well as a useful diagnostic marker for pancreatobiliary adenocarcinoma. However, its expression pattern and prognostic significance have not been studied in gallbladder adenocarcinoma. We constructed a tissue microarray from samples from 82 consecutive patients with gallbladder adenocarcinoma treated by cholecystectomy at the Kangbuk Samsung Hospital from 2000 to 2011. CK17 expression was examined by immunohistochemistry and correlated with clinicopathologic prognostic factors. CK17 stained the cytoplasm of tumor cells and immunohistochemical interpretation was possible in 77 cases. Among these, 41 (53.2%) were considered positive using a 5% cutoff determined by a receiver operating characteristic curve (area under the curve=0.656, P=0.021). CK17 expression was associated with poor tumor differentiation (P<0.001), high pT stage (P<0.001), presence of distant metastasis (P=0.036), and low disease specific survival rate (P<0.001). These results indicate that CK17 can be used as a marker for poor prognosis for gallbladder adenocarcinoma. PMID- 26990744 TI - Crizotinib Response in a Late Relapse of ALK-positive Lung Adenocarcinoma. AB - Anaplastic lymphoma kinase (ALK) rearrangement is a therapeutic target in non small cell lung cancer. To date, few reports have been provided related to ALK rearranged late recurrence and sensitivity to the treatment with specific ALK inhibitors. We report a case of a 35-year-old man who underwent a right lower lobe lobectomy for lung adenocarcinoma, and treated with the platinum-based chemotherapy regimen. After 10 healthy years, he developed a lung nodule in the same site as the previous. Cytopathologic diagnosis was lung adenocarcinoma. Furthermore, the pulmonary nodule was considered a late recurrence in relation to the lymph node involvement, the same histotype and the site, ALK fluorescence in situ hybridization test and epidermal growth factor receptor analysis were performed on the formalin-fixed paraffin-embedded specimens of the previous resected tumor, because of inadequacity cytologic sample. Being positive for ALK rearrangement, the patient was treated with crizotinib with a good response. To the best of our knowledge, it is the first case of a late relapse of ALK-positive lung adenocarcinoma sensitive to crizotinib in the literature. PMID- 26990745 TI - Immunohistochemical Expression of MCM-2 in Oral Epithelial Dysplasias. AB - BACKGROUND: Oral cancer is one of the most frequent cancers in the world. It arises from epithelial dysplasia. Hence, identifying these lesions in an early stage could prevent their malignant transformation. The aim of the present work was to assess the cell proliferative activity of minichromosome maintenance protein (MCM-2) in oral epithelial dysplastic lesions and to correlate the results with different grades of epithelial dysplasia in an attempt to use MCM-2 in the early detection of malignancy. METHODS: MCM-2 expression was determined by the nuclear count in a total of 30 oral epithelial dysplastic specimens roughly classified into 10 cases of mild, moderate, and severe dysplasia. Five cases of early invasive squamous-cell carcinomas and 5 cases of epithelial hyperplasia were also included. RESULTS: The MCM-2 immunostaining was found to increase gradually from mild to moderate to severe dysplasia and reached its maximum value in early invasive squamous cell carcinoma. CONCLUSION: MCM-2 is of prognostic value in cases of oral dysplasia that have a tendency to undergo malignant transformation. PMID- 26990746 TI - Flat Intraurothelial Neoplasia Exhibiting Diffuse Immunoreactivity for CD44 and Cytokeratin 5 (Urothelial Stem Cell/Basal Cell Markers): A Variant of Intraurothelial Neoplasia Commonly Associated With Muscle-invasive Urothelial Carcinoma. AB - BACKGROUND: Immunoreactivity for CD44 and cytokeratin (CK)5 (urothelial stem/basal cell markers) are decreased/negative in the common type of intraurothelial neoplasia including urothelial carcinomas (UC) in situ. Recent studies also reveal that a majority of muscle-invasive UC are basal-like UC with large areas of positive CD44/CK5 immunoreactivity. In addition, approximately 80% of muscle-invasive UC develop de novo as nonpapillary invasive UC. In this study, we investigate the CD44/CK5 immunoreactivity of the flat intraurothelial neoplasia (FIUN) associated with nonpapillary invasive UC. MATERIALS AND METHODS: Consecutive cases of nonpapillary UC were submitted for immunostaining. Immunostaining for CK5/CD44 was scored as high for staining of >25% thickness of urothelium and low for lesser immunoreactivity. RESULTS: In total, 109 consecutive cases were grouped into: in situ UC [carcinoma in situ (CIS)] (n=11), pT1 (n=14), and pT2-4 (n=84) with surface urothelium available for study. Forty four cases including CIS (n=9), pT1 (n=12), and pT2-4 (n=23) showed FIUN with low/negative CD44/CK5 reactivity; 40 cases showed strong CK20 reactivity. Sixty two cases including CIS (n=2), pT1 (n=2), and pT2-4 (n=58) showed extensive FIUN exhibiting high CD44/CK5 reactivity; 30 cases showed reactive CK20. FIUN lesions with high CD44/CK5 reactivity scores were associated with mild (urothelial dysplasia) to moderate atypia (CIS) and were rarely preceded by papillary UC. Most invasive UC associated with FIUN with high CD44/CK5 reactivity also exhibited extensive CD44/CK5 reactivity. The remaining 3 cases showed only reactive urothelium. Of interest, 4 cases with FIUN showed negative CD44/CK5/CK20 reactivity. CONCLUSIONS: Existence of CD44/CK5-immunoreactive (or basal-like) FIUN is consistent with the recent distinction of basal and luminal subtypes of UC. This type of FIUN is often associated with UC with progression to high-stage disease not preceded by recurrent papillary UC. PMID- 26990747 TI - The Role of Hepsin in Endometrial Carcinoma. AB - PURPOSE: Endometrial carcinoma is the sixth most common cancer in women worldwide and the most common invasive cancer of the female genital tract in developed countries. It is hoped that through a better understanding of the alterations implicated in endometrial cancer pathogenesis and prognosis, a more complete profile of risk factors and targeted therapy can be developed. Hepsin is a member of the type II transmembrane serine protease family. The importance of hepsin in prostate cancer has been demonstrated by several studies. However, the role of hepsin in endometrial carcinoma is yet to be identified. This study aimed to evaluate the immunohistochemical expression of hepsin in endometrial carcinoma, trying to explore its diagnostic and prognostic value. MATERIALS AND METHODS: This retrospective study was conducted on 27 endometrial carcinoma and 18 endometrial hyperplasia cases. Immunohistochemical expression of hepsin was evaluated in tissue specimens and results were correlated with the available clinicopathlogic parameters. RESULTS: Positive hepsin expression was seen in all (100%) carcinoma and 17/18 (94.44%) endometrial hyperplasia cases. The H-score of hepsin expression in endometrial carcinoma was significantly higher than that of hyperplasia cases (P=0.012). A significant negative association was found between hepsin expression in endometrial carcinoma cases regarding the grade and the size of tumors (P=0.018 and 0.008, respectively) as well as myometrial invasion (P=0.027). CONCLUSIONS: Hepsin could play an important role in the pathogenesis and the early carcinogenesis of endometrial carcinoma and could serve as a prognostic biomarker in this tumor. PMID- 26990748 TI - Human Cytomegalovirus is Present in Alveolar Soft Part Sarcoma. AB - Alveolar soft part sarcoma (ASPS) is an exquisitely rare sarcoma of unknown histogenesis, with a predilection for adolescents and young adults, characterized by slow progressive clinical course and high frequency of metastases. They are traditionally chemoresistant with very limited treatment options in the metastatic setting. Human cytomegalovirus (HCMV) is a DNA beta-herpes virus and it is characterized by persistent lifelong and latent infection. There is growing evidence to indicate the presence of HCMV proteins and nucleic acids in glioblastoma, medulloblastoma, rhabdomyosarcoma, and a variety of solid organ malignancies of the breast, prostate, lung, and colon at very high prevalence. Immunotherapy-based clinical trials targeting specific cytomegalovirus proteins are currently in progress in the treatment of glioblastoma. Herein, we evaluated for the presence of HCMV proteins (IE1 and pp65), genes (US28 and UL96), and RNA in a cohort of ASPS. Six confirmed cases of ASPS were retrieved and full thickness sections of formalin-fixed paraffin-embedded material were stained for anti-HMCV-IE1 and anti-HCMV-pp65. Any nuclear and/or cytoplasmic staining was considered positive. DNA was purified from 50 um of formalin-fixed paraffin embedded material. One hundred nanogram of DNA was amplified using polymerase chain reaction for primers specific to HCMV-US28 (forward: AGCGTGCCGTGTACGTTAC and reverse: ATAAAGACAAGCACGACC) and HCMV-UL96 (forward: ACAGCTCTTAAAGGACGTGATGCG and reverse: ACCGTGTCCTTCAGCTCGGTTAAA) using Promega Taq polymerase. HCMV in situ hybridization was performed. All 6 cases of ASPS were positive for both HCMV-IE1 and HCMV-pp65. Usable DNA was available in 4 of the 6 cases. HCMV-US28 gene was found in 75% (3/4) of cases and HCMV-UL96 gene was detected in 50% (2/4) of cases. Importantly, all cases tested positive for at least 1 gene. HCMV-encoded RNA was identified in 80% (4/5) of cases. The presence of HCMV DNA, RNA along with HCMV protein indicates that HCMV is present in ASPS and may contribute to its pathogenesis. PMID- 26990749 TI - Immunohistochemical Study of TGF-beta1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma: Correlations Between Clinicopathologic Factors and Overall Survival. AB - The aim of the present study was to analyze transforming growth factor beta1 (TGF beta1) expression in cases of leukoplakia and oral squamous cell carcinoma (OSCC) and to correlate these expression profiles with proliferative labeling index, clinicopathologic factors, and clinical outcome. Clinical data for 24 cases of leukoplakia and 87 cases of OSCC were retrieved from medical records. OSCC tissues were included into tissue microarray blocks and sections of normal mucosa, leukoplakia, and OSCC tissue microarray's were prepared on slides. Immunohistochemistry was used to detect expression of TGF-beta1 and Ki67. The expression of TGF-beta1 and Ki67 were significantly increased from normal mucosa, through leukoplakia to OSCC. High expression of TGF-beta1 correlated with an increase in proliferative labeling index. No association between TGF-beta1 expression and the clinicopathologic factors examined was observed. Expression of TGF-beta1 also did not associate with clinical outcome in either of groups. Our results suggest that changes in TGF-beta1 are associated with the progression of oral carcinogenesis. PMID- 26990750 TI - Nonsyndromic Intestinal Lipomas are Probably not Associated With Mutations of PDGFRA. AB - The purpose of this study was to test the hypothesis that intestinal lipomas occurring in patients devoid of signs of PDGFRA-mutant syndrome might represent sporadic counterparts of familial lipomatous tumors occurring in the spectrum of tumors associated with PDGFRA mutations. PDGFRA-mutant syndrome may manifest with gastrointestinal stromal tumors, Vanek tumors, fibrous tumors, and lipomatous tumors. Until now there has been no molecular genetic study of PDGFRA mutations in intestinal lipomas published in the world literature. A series of 20 intestinal lipomas were obtained from 17 patients, and mutational analysis of exons 12, 14, and 18 of the PDGFRA gene was performed. None of the 16 analyzable tumors showed mutations in PDGFRA. Thus, PDGFRA mutations probably do not play an important role in the development of sporadic lipomas of the intestines. PMID- 26990751 TI - Strong NFkappaB Expression is Associated With High-grade Dysplasia in Barrett's Esophagus. AB - Nuclear factor kappa B (NFkappaB) is a transcription factor that regulates the activation of genes involved in proinflammatory response and growth. In this study, we utilized immunohistochemical stains for 2 of the NFkappaB molecules (RELA and NFkappaB-1) to evaluate the expression of NFkappaB in Barrett's esophagus (BE). Forty-three cases of BE [17 cases with no dysplasia, 16 cases with low-grade dysplasia (LGD), and 10 cases with high-grade dysplasia (HGD)], 10 normal esophageal biopsies, and 9 cases of esophageal adenocarcinoma were evaluated. Expression of NFkappaB-1 and RELA did not occur in normal esophageal squamous mucosa. BE without dysplasia showed weak expression of RELA and NFkappaB 1 in 35% and 65% of cases, respectively. BE with LGD showed weak expression of RELA and NFkappaB-1 in 50% and 75% of cases, respectively. Strong expression of RELA and NFkappaB-1 did not occur in BE without dysplasia or with LGD. BE with HGD showed strong expression of RELA and NFkappaB-1 in 80% and 90% of cases, respectively. All cases of adenocarcinoma showed strong expression of both RELA and NFkappaB-1. There was a progressive increase in staining intensity of RELA and NFkappaB-1 along the metaplasia-dysplasia-adenocarcinoma pathway. Strong expression of NFkappaB is associated with HGD and adenocarcinoma (P<0.0001). We showed that strong expression of NFkappaB-1 and RELA correlates highly with BE with HGD and adenocarcinoma. PMID- 26990753 TI - The evolving landscape of imprinted genes in humans and mice: Conflict among alleles, genes, tissues, and kin. AB - Three recent genome-wide studies in mice and humans have produced the most definitive map to date of genomic imprinting (gene expression that depends on parental origin) by incorporating multiple tissue types and developmental stages. Here, we explore the results of these studies in light of the kinship theory of genomic imprinting, which predicts that imprinting evolves due to differential genetic relatedness between maternal and paternal relatives. The studies produce a list of imprinted genes with around 120-180 in mice and ~100 in humans. The studies agree on broad patterns across mice and humans including the complex patterns of imprinted expression at loci like Igf2 and Grb10. We discuss how the kinship theory provides a powerful framework for hypotheses that can explain these patterns. Finally, since imprinting is rare in the genome despite predictions from the kinship theory that it might be common, we discuss evolutionary factors that could favor biallelic expression. PMID- 26990752 TI - Soluble analog of ApoER2 targeting beta2-glycoprotein I in immune complexes counteracts hypertension in lupus-prone mice with spontaneous antiphospholipid syndrome. AB - Essentials (NZWxBXSB)F1 male mice develop antibodies beta2-glycoprotein I (beta2GPI) and hypertension. A1-A1 is a soluble analogue of ApoE receptor 2 with a high affinity for beta2GPI/antibody complexes. A1-A1 improved blood pressure and arterial elastance in (NZWxBXSB)F1 male mice. A1-A1 had no adverse effects on the hemodynamics of healthy mice. SUMMARY: Background Antiphospholipid syndrome (APS) is diagnosed based on the presence of antiphospholipid antibodies and clinical thrombosis or fetal loss during pregnancy. Lupus-prone (NZWxBXSB)F1 male mice are the mouse model of spontaneous APS. They develop anti-beta2GPI antibodies, microinfarcts and hypertension. ApoER2 is a receptor that contributes to anti-beta2GPI-dependent thrombosis in APS by down-regulating endothelial nitric oxide synthase activation. Objectives A1-A1 is a small protein constructed from two identical ligand-binding modules from ApoER2, containing the binding site for beta2GPI. We studied how treatment with A1-A1 affects the development of hypertension in (NZWxBXSB)F1 male mice. Methods We treated (NZWxBXSB)F1 male mice with A1-A1 for up to 4 weeks and examined changes in hemodynamics by left ventricular pressure-volume loop measurements. Results We observed improvements in blood pressure in the A1-A1 treated mice. A1-A1 prevented the deterioration of arterial elastance by decreasing systemic resistance and improving vessel compliance. We did not detect any adverse effects of the treatment in either male mice or in apparently healthy female (NZWxBXSB)F1 mice. Conclusions We demonstrated that A1-A1, which is a soluble analog of ApoER2 that binds pathological beta2GPI/anti-beta2GPI complexes, has a positive impact on hemodynamics in lupus-prone mice with spontaneous anti-beta2GPI antibodies and hypertension. PMID- 26990754 TI - Multiple schedules in practical application: Research trends and implications for future investigation. AB - Researchers began studying multiple schedules in basic laboratories, but recent advances have extended research on multiple schedules to a wide variety of socially significant applications, especially during the last decade. Applied researchers have used multiple schedules to (a) promote stimulus control over high-rate appropriate behaviors, (b) thin the schedule of reinforcement following functional communication training, and (c) obtain stimulus control over problem behaviors maintained by automatic reinforcement. In the current paper, we reviewed 31 studies with 147 applications identified through a search of the applied literature on multiple schedules. Using these studies, we (a) reviewed the empirical literature on multiple schedules, (b) recommended multiple-schedule procedures that serve as best practice guidelines for applied behavior analysts, (c) identified the generality and boundaries of current knowledge about the effectiveness of multiple schedules, and (d) critically analyzed the literature to provide directions for future multiple-schedule research. PMID- 26990755 TI - Symptoms of Psychopathology Within Groups of Eating-Disordered, Restrained Eating, and Unrestrained Eating Individuals. AB - OBJECTIVE: While eating-disordered individuals have shown high levels of comorbid psychopathology, there has not been an assessment of these symptoms across groups exhibiting different forms of problematic eating behavior. METHOD: Using 1,122 participants recruited via Amazon Mechanical Turk, this study examined self reported differences between controls, restrained eaters, and individuals meeting criteria for binge eating disorder and bulimia nervosa on several measures of psychopathology unrelated to eating. RESULTS: On nearly all outcome measures, eating-disordered participants had greater symptoms of psychopathology compared to restrained eaters, who had greater levels compared to controls. Among the eating-disordered participants, bulimia nervosa participants had more symptoms of psychopathology than binge eating-disordered participants. CONCLUSION: Treatment of the populations included in this study may be informed by an understanding of the different amounts of symptoms of comorbid psychopathology that confer additional distress and impairment above and beyond disordered eating behavior. PMID- 26990756 TI - 2D Mica Crystal as Electret in Organic Field-Effect Transistors for Multistate Memory. AB - Organic nonvolatile multistate storage devices based on organic field-effect transistors using mica as the 2D single-crystal electrets are developed. A4-paper sized 2D mica crystals with flat surface are prepared successfully. Devices with mica electrets exhibit a typical memory effect and show ideal output curves on both the on and the off states. PMID- 26990757 TI - Weight Loss Predicts Progression of Mild Cognitive Impairment to Alzheimer's Disease. AB - BACKGROUND: Weight loss is common in people with Alzheimer's disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown. AIMS: To assess weight loss as a predictor of dementia and AD in MCI. METHODS: One hundred twenty-five subjects with MCI (age 73.8 +/- 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a >=4% decrease in baseline weight. RESULTS: Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4 fold increased risk of dementia (95% CI = 1.5-6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4-8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD. CONCLUSIONS: Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment. PMID- 26990758 TI - Hemoglobin Decrease with Iron Deficiency Induced by Daclatasvir plus Asunaprevir Combination Therapy for Chronic Hepatitis C Virus Genotype 1b. AB - BACKGROUND: Decreased hemoglobin (Hb) level has been supposed to be a relatively rare side effect of a combination therapy against hepatitis C virus that consists of the NS5A inhibitor daclatasvir (DCV) and the NS3/4A protease inhibitor asunaprevir (ASV). METHODS: The study was conducted in 75 patients with genotype 1b chronic hepatitis C virus infection who had started combination therapy with DCV and ASV at St. Marianna University School of Medicine Hospital between September 2014 and December 2014. RESULTS: Among the patients examined, decreased Hb level by >=1.5 g/dL from the values at treatment initiation was observed in 11 individuals. This was accompanied by decreased mean corpuscular volume, and iron and ferritin levels. CONCLUSIONS: These findings suggest that the mechanism of the phenomenon is caused by iron deficiency. The underlying mechanism and clinical impacts will need to be further examined. PMID- 26990759 TI - Cytomegalovirus IgM Seroprevalence among Women of Reproductive Age in the United States. AB - Cytomegalovirus (CMV) IgM indicates recent active CMV infection. CMV IgM seroprevalence is a useful marker for prevalence of transmission. Using data from the National Health and Nutrition Examination Survey (NHANES) III 1988-1994, we present estimates of CMV IgM prevalence by race/ethnicity, provide a comparison of IgM seroprevalence among all women and among CMV IgG positive women, and explore factors possibly associated with IgM seroprevalence, including socioeconomic status and exposure to young children. There was no difference in IgM seroprevalence by race/ethnicity among all women (3.1%, 2.2%, and 1.6% for non-Hispanic white, non-Hispanic black and Mexican American, respectively; P = 0.11). CMV IgM seroprevalence decreased significantly with increasing age in non Hispanic black women (P<0.001 for trend) and marginally among Mexican American women (P = 0.07), while no apparent trend with age was seen in non-Hispanic white women (P = 0.99). Among 4001 IgG+ women, 118 were IgM+, resulting in 4.9% IgM seroprevalence. In IgG+ women, IgM seroprevalence varied significantly by age (5.3%, 7.3%, and 3.7% for women of 12-19, 20-29, and 30-49 years; P = 0.04) and race/ethnicity (6.1%, 2.7%, and 2.0% for non-Hispanic white, non-Hispanic black, and Mexican American; P<0.001). The factors reported associated with IgG seroprevalence were not associated with IgM seroprevalence. The patterns of CMV IgM seroprevalence by age, race/ethnicity, and IgG serostatus may help understanding the epidemiology of congenital CMV infection as a consequence of vertical transmission and are useful for identifying target populations for intervention to reduce CMV transmission. PMID- 26990760 TI - Oral Immunization with OspC Does Not Prevent Tick-Borne Borrelia burgdorferi Infection. AB - Oral vaccination strategies are of interest to prevent transmission of Lyme disease as they can be used to deliver vaccines to humans, pets, and to natural wildlife reservoir hosts of Borrelia burgdorferi. We developed a number of oral vaccines based in E. coli expressing recombinant OspC type K, OspB, BBK32 from B. burgdorferi, and Salp25, Salp15 from Ixodes scapularis. Of the five immunogenic candidates only OspC induced significant levels of antigen-specific IgG and IgA when administered to mice via the oral route. Antibodies to OspC did not prevent dissemination of B. burgdorferi as determined by the presence of spirochetes in ear, heart and bladder tissues four weeks after challenge. Next generation sequencing of genomic DNA from ticks identified multiple phyletic types of B. burgdorferi OspC (A, D, E, F, I, J, K, M, Q, T, X) in nymphs that engorged on vaccinated mice. PCR amplification of OspC types A and K from flat and engorged nymphal ticks, and from heart and bladder tissues collected after challenge confirmed sequencing analysis. Quantification of spirochete growth in a borreliacidal assay shows that both types of spirochetes (A and K) survived in the presence of OspC-K specific serum whereas the spirochetes were killed by OspA specific serum. We show that oral vaccination of C3H-HeN mice with OspC-K induced significant levels of antigen-specific IgG. However, these serologic antibodies did not protect mice from infection with B. burgdorferi expressing homologous or heterologous types of OspC after tick challenge. PMID- 26990761 TI - Is Myomectomy Prior to Assisted Reproductive Technology Cost Effective in Women with Intramural Fibroids? AB - AIM: To evaluate the cost effectiveness of surgery to remove intramural (IM) fibroids prior to assisted reproductive technology (ART). METHODS: The decision tree mathematical model along with sensitivity analysis was performed to analyze cost effectiveness of: (1) myomectomy followed by ART or (2) ART with IM myoma(s) in situ. RESULTS: At the median ongoing pregnancy (OP) rate (OPR) reported in the literature for a fresh, autologous ART cycle with IM fibroids in situ vs. post-IM myomectomy, average cost per OP was $72,355 vs. 66,075, indicating a cost savings with myomectomy. Sensitivity analysis over the range of reported OPRs demonstrated that pre-ART IM myomectomy was always cost effective when OPR among women with in situ myomas was <15.4%. However, for OPRs >=15.4%, pre-ART IM myomectomy was only cost effective if it increased OPR by at least 9.6%. At the high end of OPRs reported for patients with IM myomas in situ (31.4%), a 19.5% improvement in OPR was needed to justify IM myomectomy from a cost perspective. CONCLUSION: Myomectomy should be used sparingly in cases where the goal of surgery is to achieve improvement in the outcomes of ART. PMID- 26990762 TI - Neonatal respiratory syncytial virus infection has an effect on lung inflammation and the CD4(+) CD25(+) T cell subpopulation during ovalbumin sensitization in adult mice. AB - In BALB/c adult mice, respiratory syncytial virus (RSV) infection enhances the degree of lung inflammation before and/or after ovalbumin (OVA) respiratory sensitization. However, it is unclear whether RSV infection in newborn mice has an effect on the immune response to OVA respiratory sensitization in adult mice. The aim of this study was to determine if RSV neonatal infection alters T CD4(+) population and lung inflammation during OVA respiratory sensitization in adult mice. BALB/c mice were infected with RSV on the fourth day of life and challenged by OVA 4 weeks later. We found that in adult mice, RSV neonatal infection prior to OVA sensitization reduces the CD4(+) CD25(+) and CD4(+) CD25(+) forkhead protein 3 (FoxP3)(+) cell populations in the lungs and bronchoalveolar lavage. Furthermore, it also attenuates the inflammatory infiltrate and cytokine/chemokine expression levels in the mouse airways. In conclusion, the magnitude of the immune response to a non-viral respiratory perturbation in adult mice is not enhanced by a neonatal RSV infection. PMID- 26990763 TI - Real-Time In Vivo Confocal Fluorescence Imaging of Prostate Cancer Bone-Marrow Micrometastasis Development at the Cellular Level in Nude Mice. AB - In the present report, we demonstrate in vivo fluorescence imaging of bone-marrow micrometastasis of prostate cancer at the cellular level in nude mice. PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) or red fluorescent protein (RFP) were injected into the left ventricle or intratibial bone marrow of nude mice. PC-3-GFP, as well as selected high metastatic variants of PC-3-GFP, PC-3-GFP-BM6 or PC-3-RFP were visualized by real-time fluorescence imaging, to traffic and grow in the bone marrow. Formation of bone marrow micrometastasis could be imaged at the single-cell level in live mice, using confocal microscopy. The ability to track bone marrow micrometastasis in real time at the cellular level provides a visual target for evaluating new therapeutics for this recalcitrant disease. J. Cell. Biochem. 117: 2533-2537, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990764 TI - Nicotinamide Cofactors Suppress Active-Site Labeling of Aldehyde Dehydrogenases. AB - Active site labeling by (re)activity-based probes is a powerful chemical proteomic tool to globally map active sites in native proteomes without using substrates. Active site labeling is usually taken as a readout for the active state of the enzyme because labeling reflects the availability and reactivity of active sites, which are hallmarks for enzyme activities. Here, we show that this relationship holds tightly, but we also reveal an important exception to this rule. Labeling of Arabidopsis ALDH3H1 with a chloroacetamide probe occurs at the catalytic Cys, and labeling is suppressed upon nitrosylation and oxidation, and upon treatment with other Cys modifiers. These experiments display a consistent and strong correlation between active site labeling and enzymatic activity. Surprisingly, however, labeling is suppressed by the cofactor NAD(+), and this property is shared with other members of the ALDH superfamily and also detected for unrelated GAPDH enzymes with an unrelated hydantoin-based probe in crude extracts of plant cell cultures. Suppression requires cofactor binding to its binding pocket. Labeling is also suppressed by ALDH modulators that bind at the substrate entrance tunnel, confirming that labeling occurs through the substrate binding cavity. Our data indicate that cofactor binding adjusts the catalytic Cys into a conformation that reduces the reactivity toward chloroacetamide probes. PMID- 26990765 TI - The Impact of Dietary and Metabolic Risk Factors on Cardiovascular Diseases and Type 2 Diabetes Mortality in Brazil. AB - BACKGROUND: Trends in food availability and metabolic risk factors in Brazil suggest a shift toward unhealthy dietary patterns and increased cardiometabolic disease risk, yet little is known about the impact of dietary and metabolic risk factors on cardiometabolic mortality in Brazil. METHODS: Based on data from Global Burden of Disease (GBD) Study, we used comparative risk assessment to estimate the burden of 11 dietary and 4 metabolic risk factors on mortality due to cardiovascular diseases and diabetes in Brazil in 2010. Information on national diets and metabolic risks were obtained from the Brazilian Household Budget Survey, the Food and Agriculture Organization database, and large observational studies including Brazilian adults. Relative risks for each risk factor were obtained from meta-analyses of randomized trials or prospective cohort studies; and disease-specific mortality from the GBD 2010 database. We quantified uncertainty using probabilistic simulation analyses, incorporating uncertainty in dietary and metabolic data and relative risks by age and sex. Robustness of findings was evaluated by sensitivity to varying feasible optimal levels of each risk factor. RESULTS: In 2010, high systolic blood pressure (SBP) and suboptimal diet were the largest contributors to cardiometabolic deaths in Brazil, responsible for 214,263 deaths (95% uncertainty interval [UI]: 195,073 to 233,936) and 202,949 deaths (95% UI: 194,322 to 211,747), respectively. Among individual dietary factors, low intakes of fruits and whole grains and high intakes of sodium were the largest contributors to cardiometabolic deaths. For premature cardiometabolic deaths (before age 70 years, representing 40% of cardiometabolic deaths), the leading risk factors were suboptimal diet (104,169 deaths; 95% UI: 99,964 to 108,002), high SBP (98,923 deaths; 95%UI: 92,912 to 104,609) and high body-mass index (BMI) (42,643 deaths; 95%UI: 40,161 to 45,111). CONCLUSION: suboptimal diet, high SBP, and high BMI are major causes of cardiometabolic death in Brazil, informing priorities for policy initiatives. PMID- 26990768 TI - Biosensor cell assay for measuring real-time aldosterone-induced release of histamine from mesenteric arteries. AB - AIMS: The aims were to develop a method for real-time detection of histamine release and to test whether incubation with aldosterone induces histamine release from isolated, perfused mice mesenteric arteries. METHODS: Fura-2-loaded HEK-293 cells transfected with the histamine H1 receptor was used as a sensitive biosensor assay for histamine release from isolated mouse mesenteric arteries. Activation of the H1 receptor by histamine was measured as an increased number of intracellular Ca2+ transient peaks using fluorescence imaging. RESULTS: The developed biosensor was sensitive to histamine in physiological relevant concentrations and responded to substances released by the artery preparation. Aldosterone treatment of mesenteric arteries from wild-type mice for 50 min resulted in an increased number of intracellular Ca2+ transient peaks in the biosensor cells, which was significantly inhibited by the histamine H1 blocker pyrilamine. Mesenteric arteries from mast cell-deficient SASH mice induced similar pyrilamine-sensitive Ca2+ transient response in the biosensor cells. Mesenteric arteries from wild-type and SASH mice expressed histamine decarboxylase mRNA, indicating that mast cells are not the only source of histamine release. CONCLUSION: The developed biosensor assay can measure release of substances from vascular preparations. Histamine is released from the vessel preparation in response to aldosterone treatment independently of mast cells. The assay enables us to study a new signaling mechanism for vascular responses induced by aldosterone. PMID- 26990766 TI - A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa Induced Dyskinesia. AB - BACKGROUND: This phase 2 randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the nicotinic acetylcholine receptor alpha7 agonist AQW051 in patients with Parkinson's disease and levodopa-induced dyskinesia. METHODS: Patients with idiopathic Parkinson's disease and moderate to severe levodopa-induced dyskinesia were randomized to AQW051 10 mg (n = 24), AQW051 50 mg (n = 24), or placebo (n = 23) once daily for 28 days. Coprimary end points were change in Modified Abnormal Involuntary Movement Scale and Unified Parkinson's Disease Rating Scale part III scores. Secondary outcomes included pharmacokinetics. RESULTS: In total, 67 patients completed the study. AQW051 treated patients experienced no significant improvements in Modified Abnormal Involuntary Movement Scale or Unified Parkinson's Disease Rating Scale part III scores by day 28. AQW051 was well tolerated; the most common adverse events were dyskinesia, fatigue, nausea, and falls. CONCLUSIONS: AQW051 did not significantly reduce dyskinesia or parkinsonian severity. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26990769 TI - Extensive Acclimation in Ectotherms Conceals Interspecific Variation in Thermal Tolerance Limits. AB - Species' tolerance limits determine their capacity to tolerate climatic extremes and limit their potential distributions. Interspecific variation in thermal tolerances is often proposed to indicate climatic vulnerability and is, therefore, the subject of many recent meta-studies on differential capacities of species from climatically different habitats to deal with climate change. Most studies on thermal tolerances do not acclimate animals or use inconsistent, and insufficient, acclimation times, limiting our knowledge of the shape, duration and extent of acclimation responses. Consequently patterns in thermal tolerances observed in meta-analyses, based on data from the literature are based on inconsistent, partial acclimation and true trends may be obscured. In this study we describe time-course of complete acclimation of critical thermal minima in the tropical ectotherm Carlia longipes and compare it to the average acclimation response of other reptiles, estimated from published data, to assess how much acclimation time may contribute to observed differences in thermal limits. Carlia longipes decreased their lower critical thermal limits by 2.4 degrees C and completed 95% of acclimation in 17 weeks. Wild populations did not mirror this acclimation process over the winter. Other reptiles appear to decrease cold tolerance more quickly (95% in 7 weeks) and to a greater extent, with an estimated average acclimation response of 6.1 degrees C. However, without data on tolerances after longer acclimation times available, our capacity to estimate final acclimation state is very limited. Based on the subset of data available for meta-analysis, much of the variation in cold tolerance observed in the literature can be attributed to acclimation time. Our results indicate that (i) acclimation responses can be slow and substantial, even in tropical species, and (ii) interspecific differences in acclimation speed and extent may obscure trends assessed in some meta-studies. Cold tolerances of wild animals are representative of cumulative responses to recent environments, while lengthy acclimation is necessary for controlled comparisons of physiological tolerances. Measures of inconsistent, intermediate acclimation states, as reported by many studies, represent neither the realised nor the potential tolerance in that population, are very likely underestimates of species' physiological capacities and may consequently be of limited value. PMID- 26990770 TI - Evaluation of the Intestinal Absorption Mechanism of Casearin X in Caco-2 Cells with Modified Carboxylesterase Activity. AB - The clerodane diterpene casearin X (1), isolated from the leaves of Casearia sylvestris, is a potential new drug candidate due to its potent in vitro cytotoxic activity. In this work, the intestinal absorption mechanism of 1 was evaluated using Caco-2 cells with and without active carboxylesterases (CES). An LC-MS method was developed and validated for the quantification of 1. The estimation of permeability coefficients was possible only under CES-inhibited conditions in which 1 is able to cross the Caco-2 cell monolayer. The mechanism is probably by active transport, with no significant efflux, but with a high retention of the compound inside the cells. The enzymatic hydrolysis assay demonstrates the susceptibility of 1 to first-pass metabolism as substrate for specific CES expressed in human intestine. PMID- 26990771 TI - Molecular epidemiology identifies HIV transmission networks associated with younger age and heterosexual exposure among Korean individuals. AB - To evaluate if HIV transmission networks could be elucidated from data collected in a short time frame, 131 HIV-1 pol sequences were analyzed which were generated from treatment-naive Korean individuals who were sequentially identified over 1 year. A transmission linkage was inferred when there was a genetic distance <1.5% and a total of 16 clusters, involving 39/131 (29.8%), were identified. Younger age and heterosexual exposure were independently related with clustering in the inferred network, which demonstrated that molecular epidemiology with currently generated data (i.e., drug resistance genotypes) can be used to identify local transmission networks, even over a short timeframe. J. Med. Virol. 88:1832-1835, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990773 TI - Bayesian joint modeling of longitudinal and spatial survival AIDS data. AB - Joint analysis of longitudinal and survival data has received increasing attention in the recent years, especially for analyzing cancer and AIDS data. As both repeated measurements (longitudinal) and time-to-event (survival) outcomes are observed in an individual, a joint modeling is more appropriate because it takes into account the dependence between the two types of responses, which are often analyzed separately. We propose a Bayesian hierarchical model for jointly modeling longitudinal and survival data considering functional time and spatial frailty effects, respectively. That is, the proposed model deals with non-linear longitudinal effects and spatial survival effects accounting for the unobserved heterogeneity among individuals living in the same region. This joint approach is applied to a cohort study of patients with HIV/AIDS in Brazil during the years 2002-2006. Our Bayesian joint model presents considerable improvements in the estimation of survival times of the Brazilian HIV/AIDS patients when compared with those obtained through a separate survival model and shows that the spatial risk of death is the same across the different Brazilian states. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990774 TI - Specific characterization of non-steroidal selective androgen peceptor modulators using supercritical fluid chromatography coupled to ion-mobility mass spectrometry: application to the detection of enobosarm in bovine urine. AB - Currently under development for therapeutic purposes in human medicine, non steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth associated pathways. As such, they present a potential for abuse in sports and food-producing animals as interesting alternative anabolic substances. Forbidden since 2008 by the World Anti-Doping Agency (WADA) these compounds are however easily available and could be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies have to be developed for specific and sensitive detection of these compounds in biological matrices. Using an innovative analytical platform constituted of supercritical fluid chromatography coupled to ion mobility-mass spectrometry, the present study enabled efficient separation and identification in urine of 4 of these drugs (andarine, bicalutamide, hydroxyflutamide, and enobosarm) in accordance with European Union criteria (Commission Decision 2002/657/EC). Besides providing information about compounds structure and behaviour in gas phase, such a coupling enabled reaching low limits of detection (LOD < 0.05 ng.mL-1 for andarine and limits of detection < 0.005 ng.mL-1 for the three others) in urine with good repeatability (CV < 21 %). The workflow has been applied to quantitative determination of enobosarm elimination in urine of treated bovine (200 mg, oral). Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990767 TI - Neuroinflammation: the devil is in the details. AB - There is significant interest in understanding inflammatory responses within the brain and spinal cord. Inflammatory responses that are centralized within the brain and spinal cord are generally referred to as 'neuroinflammatory'. Aspects of neuroinflammation vary within the context of disease, injury, infection, or stress. The context, course, and duration of these inflammatory responses are all critical aspects in the understanding of these processes and their corresponding physiological, biochemical, and behavioral consequences. Microglia, innate immune cells of the CNS, play key roles in mediating these neuroinflammatory responses. Because the connotation of neuroinflammation is inherently negative and maladaptive, the majority of research focus is on the pathological aspects of neuroinflammation. There are, however, several degrees of neuroinflammatory responses, some of which are positive. In many circumstances including CNS injury, there is a balance of inflammatory and intrinsic repair processes that influences functional recovery. In addition, there are several other examples where communication between the brain and immune system involves neuroinflammatory processes that are beneficial and adaptive. The purpose of this review is to distinguish different variations of neuroinflammation in a context specific manner and detail both positive and negative aspects of neuroinflammatory processes. In this review, we will use brain and spinal cord injury, stress, aging, and other inflammatory events to illustrate the potential harm and benefits inherent to neuroinflammation. Context, course, and duration of the inflammation are highly important to the interpretation of these events, and we aim to provide insight into this by detailing several commonly studied insults. This article is part of the 60th anniversary supplemental issue. PMID- 26990772 TI - A Hypomorphic PALB2 Allele Gives Rise to an Unusual Form of FA-N Associated with Lymphoid Tumour Development. AB - Patients with biallelic truncating mutations in PALB2 have a severe form of Fanconi anaemia (FA-N), with a predisposition for developing embryonal-type tumours in infancy. Here we describe two unusual patients from a single family, carrying biallelic PALB2 mutations, one truncating, c.1676_1677delAAinsG;(p.Gln559ArgfsTer2), and the second, c.2586+1G>A; p.Thr839_Lys862del resulting in an in frame skip of exon 6 (24 amino acids). Strikingly, the affected individuals did not exhibit the severe developmental defects typical of FA-N patients and initially presented with B cell non-Hodgkin lymphoma. The expressed p.Thr839_Lys862del mutant PALB2 protein retained the ability to interact with BRCA2, previously unreported in FA-N patients. There was also a large increased chromosomal radiosensitivity following irradiation in G2 and increased sensitivity to mitomycin C. Although patient cells were unable to form Rad51 foci following exposure to either DNA damaging agent, U2OS cells, in which the mutant PALB2 with in frame skip of exon 6 was induced, did show recruitment of Rad51 to foci following damage. We conclude that a very mild form of FA-N exists arising from a hypomorphic PALB2 allele. PMID- 26990776 TI - PyGlobal: A toolkit for automated compilation of DFT-based descriptors. AB - Density Functional Theory (DFT)-based Global reactivity descriptor calculations have emerged as powerful tools for studying the reactivity, selectivity, and stability of chemical and biological systems. A Python-based module, PyGlobal has been developed for systematically parsing a typical Gaussian outfile and extracting the relevant energies of the HOMO and LUMO. Corresponding global reactivity descriptors are further calculated and the data is saved into a spreadsheet compatible with applications like Microsoft Excel and LibreOffice. The efficiency of the module has been accounted by measuring the time interval for randomly selected Gaussian outfiles for 1000 molecules. (c) 2016 Wiley Periodicals, Inc. PMID- 26990775 TI - Adenoviral vector encoding soluble Flt-1 engineered human endometrial mesenchymal stem cells effectively regress endometriotic lesions in NOD/SCID mice. AB - This study was undertaken to study the efficiency of Adsflt-1 engineered human eutopic mesenchymal stem cells (MSCs) secreting anti-angiogenic sFlt-1 as a targeted cell-based therapy for endometriosis (EM). Eutopic MSCs were transduced with Adsflt-1/AdV0 viral vectors and were evaluated for expression and secretion of sFlt-1. EM was created in NOD/SCID mice using subcutaneous implantation techniques. Four doses of 10(6) MSC-Adsflt-1/MSC-AdV0 were administered to the model and therapeutic anti-angiogenic ability was analyzed by lesion size measurement, microvessel density, immunohistochemistry and real-time reverse transcriptase-PCR analysis. Approximately 86% of transduced MSCs expressed and secreted sFlt-1. MSC-Adsflt-1-treated animals exhibited significant reduction (52.8+/-1.8%) in size of endometriotic lesions. We observed a 2.3-fold decrease in the number and a 10-fold decrease in the size of endometrial glands in MSC Adsflt-1-treated animals. A two-fold decrease in stromal cell densities was also observed in MSC-Adsflt-1-treated animals compared with the MSC-AdV0 group. Specific positive immunostaining for MSC marker, CD146 and sFlt-1 in the lesion sites of the MSC-Adsflt-1 group suggests possible homing of transduced MSCs, their survival and secretion of sFlt-1 at the target sites. A marked reduction in size of microvessels and microvessel density within endometriotic lesions and surrounding host subcutaneous layers was observed in MSC-Adsflt-1 group along with significantly downregulated expression of transcripts for vascular endothelial growth factor, fetal liver kinase 1 and matrix metalloproteinases (2 and 9). Our findings indicate the efficacy of a novel eutopic MSC-Adsflt-1 therapy in EM study models. Evaluating long-term effects of genetically modified MSCs in vivo is essential in translating MSC-Adsflt-1 therapy to the clinics. PMID- 26990777 TI - Antimelanogenic effect of 4-hydroxylonchocarpin through the inhibition of tyrosinase-related proteins and MAPK phosphatase. PMID- 26990778 TI - Smoking-Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink. AB - OBJECTIVE: To investigate the association between smoking status and smoking cessation with mortality in patients with rheumatoid arthritis (RA). METHODS: An incident cohort of patients with RA was identified using the Clinical Practice Research Datalink, a database of UK primary care electronic medical records. Time varying smoking status, years of cessation, and amount smoked were determined from patients' medical records. The date and underlying cause of death were identified by linkage with Office for National Statistics records. The associations between smoking status and smoking cessation with all-cause and cause-specific mortality (circulatory disease, all cancers, lung cancer, respiratory disease, and respiratory infection) were investigated using adjusted Cox (all-cause mortality) and Fine-Gray (cause-specific mortality) regression. RESULTS: The cohort comprised 5,677 patients (median age 61.4 years, 68% women), with 40% as never smokers, 34% former smokers, and 26% current smokers at baseline. Compared to never smoking, current smoking was associated with an increased risk of all-cause mortality (hazard ratio 1.98 [95% confidence interval (95% CI) 1.56, 2.53]), and mortality due to circulatory disease (subdistribution hazard ratio [SHR] 1.96 [95% CI 1.33, 2.90]) and lung cancer (SHR 23.2 [95% CI 5.15, 105]). Each year of smoking cessation was associated with a decreased risk of all-cause mortality (former heavy smokers SHR 0.85 [95% CI 0.77, 0.94], former light smokers SHR 0.90 [95% CI 0.84, 0.97]). CONCLUSION: Current smoking is associated with an increased risk of all-cause, cardiovascular, and lung cancer mortality in patients with RA. Each year of cessation is associated with a reduced risk of all-cause mortality. This information may prove helpful in smoking cessation programs for patients with RA. PMID- 26990781 TI - Nonpharmaceutical Pain Control Adjuncts During First-Trimester Aspiration Abortion: A Review. AB - INTRODUCTION: First-trimester aspiration abortion is associated with moderate to severe pain. The effectiveness of adjunctive therapies for pain control is not well understood. This critical review summarizes the existing literature regarding nonpharmacologic interventions to reduce pain during first-trimester office-based abortion. METHODS: PubMed and Google Scholar were searched using the following search terms in various combinations: "abortion," "pain," "nonpharmaceutical," "nonpharmacologic," "anxiety," "fear," "pain management," "pain reduction," "anxiety reduction," "complementary and alternative medicine," and "integrative medicine." Seven articles meeting inclusion criteria were entered into a matrix for comparison. Findings from each study are summarized describing design, results, and themes. These results are summarized to provide evidence-based clinical guidelines and identify areas for further research. RESULTS: None of the nonpharmacologic interventions studied were significantly associated with a reduction in pain or anxiety scores. However, women in many studies strongly endorsed future use of these techniques. DISCUSSION: The data included in this critical review did not demonstrate a relationship between the nonpharmacologic interventions and pain or anxiety scores, yet participants endorsed these as positive and helpful. Women found value in these supportive interventions, and ongoing investigation into these techniques is warranted. PMID- 26990780 TI - Acyclic Cucurbit[n]uril-Type Molecular Containers: Influence of Linker Length on Their Function as Solubilizing Agents. AB - Two acyclic cucurbit[n]uril (CB[n])-type molecular containers that differ in the length of the (CH2 )n linker (M2C2: n=2, M2C4: n=4) between their aromatic sidewalls and sulfonate solubilizing groups were prepared and studied. The inherent solubilities of M2C2 (68 mm) and M2C4 (196 mm) are higher than the analogue with a (CH2 )3 linker (M2, 14 mm) studied previously. (1) H NMR dilution experiments show that M2C2 and M2C4 do not self-associate in water, which enables their use as solubilizing excipients. We used phase solubility diagrams (PSDs) to compare the solubilizing capacities of M2, M2C2, M2C4, hydroxypropyl-beta cyclodextrin (HP-beta-CD), and sulfobutylether-beta-cyclodextrin (SBE-beta-CD) toward 15 insoluble drugs. We found that M2C2 and M2C4-as gauged by the slope of their PSDs-are less potent solubilizing agents than M2. However, the higher inherent solubility of M2C2 allows higher concentrations of drug to be formulated using M2C2 than with M2 in several cases. The solubilizing ability of M2C2 and SBE-beta-CD were similar in many cases, with Krel values averaging 23 and 12, respectively, relative to HP-beta-CD. In vitro cytotoxicity and in vivo maximum tolerated dose studies document the biocompatibility of M2C2. PMID- 26990779 TI - Quantitative neuroanatomy for connectomics in Drosophila. AB - Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity. PMID- 26990783 TI - Mandibular advancement splints decrease blood pressure similarly as with continuous positive airway pressure in sleep apnea. PMID- 26990784 TI - Evaluation of lifting and antiwrinkle effects of calcium hydroxylapatite filler. In vitro quantification of contractile forces of human wrinkle and normal aged fibroblasts treated with calcium hydroxylapatite. AB - BACKGROUND: As it ages, the skin changes, it loses its natural hydration and its fundamental substance degenerates. Due to a lack of hydration and nutrients, collagen production decreases. This support tissue of the skin weakens, losing tone and firmness. Depressions form on the skin's surface: these are wrinkles. Wrinkles are one of the first visible signs of the skin's aging, and mainly occur on the face. OBJECTIVES: The purpose of the study was firstly to study the differences between contractile forces developed by normal aged fibroblasts (NF) and wrinkle fibroblasts (WF) of the same patients evaluating the loss of skin tone and secondly to evaluate the effects of a filler composed of calcium hydroxylapatite (CaHa) on the development of contractile forces of NF and WF. METHODS: Biopsies were performed on wrinkled and normal aged skin of facelifts of three patients. The forces generated by the both fibroblast lines in tense collagen lattices were quantified using GlaSbox device before and after the addition of a mixture composed of CaHa. RESULTS: The forces developed by WF were significantly lower than those of NF. In the presence of the mixture with CaHa, the contractile forces developed by normal NF were significantly increased. WF treated with CaHa also developed higher contractile forces in comparison with nontreated WF. CONCLUSION: The mixture composed of CaHa tends to restore the contractile properties of WF to the same level as NF. Therefore, this study shows that CaHa has positive overall effects on aging. PMID- 26990782 TI - 90-yttrium-ibritumomab tiuxetan consolidation of fludarabine, mitoxantrone, rituximab in intermediate/high-risk follicular lymphoma: updated long-term results after a median follow-up of 7 years. AB - Radioimmunotherapy (RIT) after an induction phase with conventional chemoimmunotherapy became an attractive strategy of consolidation for patients with advanced follicular lymphoma: in particular, in many studies RIT was represented by yttrium-90-ibritumomab tiuxetan ((90) Y-IT). Independently by the different front-line treatment, updates on the long-term follow-up of these studies are needed because the disease course of follicular lymphoma is characterised by multiple relapses and progressively shorter durations of response. We report updated long-term efficacy and toxicity results of a multicenter phase II study on sequential treatment with four cycles of fludarabine, mitoxantrone, and rituximab followed by (90) Y-IT as front-line therapy for untreated patients with intermediate/high-risk follicular lymphoma. With a median follow-up of 84 months, only 19/49 (38.8%) complete response patients relapsed, yielding an estimated long-term disease-free survival of 62.6%. The 7-year overall survival was 72.7%. Four (7.3%) second acute myeloid leukemia occurred, with a median time following RIT of 42 months. A relevant patients' responsiveness to subsequent therapies occurred: approximately 65% of relapsed patients obtained a good clinical response after the second-line treatment. These data represented the first evidence of a real role even in the long period of 90Y-IT after a fludarabine-containing regimen plus rituximab in the treatment of high-risk follicular lymphoma. PMID- 26990785 TI - Molecular Effects of Neonicotinoids in Honey Bees (Apis mellifera). AB - Neonicotinoids are implicated in the decline of bee populations. As agonists of nicotinic acetylcholine receptors, they disturb acetylcholine receptor signaling leading to neurotoxicity. Several behavioral studies showed the link between neonicotinoid exposure and adverse effects on foraging activity and reproduction. However, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic levels of three neonicotinoids and nicotine, and compared laboratory studies to field exposures with acetamiprid. We assessed transcriptional alterations of eight selected genes in caged honey bees exposed to different concentrations of the neonicotinoids acetamiprid, clothianidin, imidacloporid, and thiamethoxam, as well as nicotine. We determined transcripts of several targets, including nicotinic acetylcholine receptor alpha 1 and alpha 2 subunit, the multifunctional gene vitellogenin, immune system genes apidaecin and defensin-1, stress-related gene catalase and two genes linked to memory formation, pka and creb. Vitellogenin showed a strong increase upon neonicotinoid exposures in the laboratory and field, while creb and pka transcripts were down-regulated. The induction of vitellogenin suggests adverse effects on foraging activity, whereas creb and pka down-regulation may be implicated in decreased long-term memory formation. Transcriptional alterations occurred at environmental concentrations and provide an explanation for the molecular basis of observed adverse effects of neonicotinoids to bees. PMID- 26990786 TI - Group cell phones are feasible and acceptable for promoting optimal breastfeeding practices in a women's microcredit program in Nigeria. AB - As part of a breastfeeding promotion intervention trial in Nigeria, we provided one cell phone per group of 5-7 microcredit clients and instructed the group's cell phone recipient to share weekly breastfeeding voice and text messages with group members. We measured the feasibility and acceptability of using group cell phones by conducting semi-structured exit interviews with 195 microcredit clients whose babies were born during the intervention (target group), in-depth interviews with eight phone recipients and nine non-phone recipients, and 16 focus group discussions with other microcredit clients. Women in the target group said the group phone worked well or very well (64%). They were motivated to try the recommended practices because they trusted the information (58%) and had support from others (35%). Approximately 44% of target women reported that their groups met and shared messages at least once a week. Women in groups that met at least weekly had higher odds of exclusive breastfeeding up to 6 months (OR 5.6, 95% CI 1.6, 19.7) than women in groups that never met. In-depth interviews and focus group discussions indicated that non-phone recipients had positive feelings towards phone recipients, the group phone met participants' needs, and messages were often shared outside the group. In conclusion, group cell phone messaging to promote breastfeeding among microcredit clients is feasible and acceptable and can be part of an effective behaviour change package. PMID- 26990787 TI - White Light Emissive Dy(III) Single-Molecule Magnets Sensitized by Diamagnetic [Co(III) (CN)6 ](3-) Linkers. AB - The self-assembly of Dy(III) -3-hydroxypyridine (3-OHpy) complexes with hexacyanidocobaltate(III) anions in water produces cyanido-bridged {[Dy(III) (3 OHpy)2 (H2 O)4 ] [Co(III) (CN)6 ]}?H2 O (1) chains. They reveal a single-molecule magnet (SMM) behavior with a large zero direct current (dc) field energy barrier, DeltaE=266(12) cm(-1) (~385 K), originating from the single-ion property of eight coordinated Dy(III) of an elongated dodecahedral geometry, which are embedded with diamagnetic [Co(III) (CN)6 ](3-) ions into zig-zag coordination chains. The SMM character is enhanced by the external dc magnetic field, which results in the DeltaE of 320(23) cm(-1) (~460 K) at Hdc =1 kOe, and the opening of a butterfly hysteresis loop below 6 K. Complex 1 exhibits white Dy(III) -based emission realized by energy transfer from Co(III) and 3-OHpy to Dy(III) . Low temperature emission spectra were correlated with SMM property giving the estimation of the zero field DeltaE. 1 is a unique example of bifunctional magneto-luminescent material combining white emission and slow magnetic relaxation with a large energy barrier, both controlled by rich structural and electronic interplay between Dy(III) , 3-OHpy, and [Co(III) (CN)6 ](3-) . PMID- 26990789 TI - Health state utilities in non-small cell lung cancer: An international study. AB - AIM: Quality of life weights (utilities) are an important input in economic evaluation and evidence suggests that there can be important differences between countries. This study was designed to capture utilities for metastatic non-small cell lung cancer and common grade III/IV toxicities associated with treatment from local populations in the United Kingdom, Australia, France, China, Taiwan, and Korea. Toxicities included neutropenia, febrile neutropenia, fatigue, diarrhea, nausea and vomiting, rash, bleeding, hypertension, and hair loss. METHODS: Existing health state descriptions of non-small cell lung cancer were adapted to represent descriptions of patients on first-line treatment. Twenty three states were translated and assessed in cognitive debrief content validation interviews with oncologists in each country. Seventy-five respondents per country completed a time trade-off interview to evaluate the states. Variation between countries for all states was explored with a Generalized Estimating Equations model. RESULTS: The mean utility for "stable disease and no side effects" (base state) varied between 0.84 (United Kingdom) and 0.54 (Taiwan). The largest utility decrements were found for febrile neutropenia (0.47) and neutropenia (0.35) across all countries. Asian countries regarded bleeds as a severe toxicity whereas non-Asian countries did not and valued diarrhea and fatigue as more severe. Significant differences in utilities between countries emerged with the Taiwanese population in particular rating states as significantly worse than other countries. CONCLUSION: This study improves our understanding of how utilities for the same states can vary across countries. The study shows the importance of capturing utilities that reflect the preferences of the local population. PMID- 26990790 TI - Generalized Student's t-distribution mixtures for autoradiographic image spread modelling. AB - In this paper, a new class of models for autoradiographic hot-line data is proposed. The models, for which there is theoretical justification, are a linear combination of generalized Student's t-distributions and have as special cases all currently accepted line-spread models. The new models are used to analyse experimental hot-line data and compared with the fit of current models. The data are from a line source labelled with iodine-125 in a resin section of 0.6 MUm in thickness. It will be shown that a significant improvement in goodness of fit, over that of previous models, can be achieved by choosing from this new class of models. A single model from this class will be proposed that has a simple form made up of only two components, but which fits experimental data significantly better than previous models. A short sensitivity analysis indicates that estimation is reliable. The modelling approach, although motivated by and applied to autoradiography, is appropriate for any mixture modelling situation. PMID- 26990788 TI - On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain order parameters. AB - Molecular dynamics (MD) simulations have become a central tool for investigating various biophysical questions with atomistic detail. While many different proxies are used to qualify MD force fields, most are based on largely structural parameters such as the root mean square deviation from experimental coordinates or nuclear magnetic resonance (NMR) chemical shifts and residual dipolar couplings. NMR derived Lipari-Szabo squared generalized order parameter (O(2) ) values of amide N?H bond vectors of the polypeptide chain were also often employed for refinement and validation. However, with a few exceptions, side chain methyl symmetry axis order parameters have not been incorporated into experimental reference sets. Using a test set of five diverse proteins, the performance of several force fields implemented in the NAMDD simulation package was examined. It was found that simulations employing explicit water implemented using the TIP3 model generally performed significantly better than those using implicit water in reproducing experimental methyl symmetry axis O(2) values. Overall the CHARMM27 force field performs nominally better than two implementations of the Amber force field. It appeared that recent quantum mechanics modifications to side chain torsional angles of leucine and isoleucine in the Amber force field have significantly hindered proper motional modeling for these residues. There remained significant room for improvement as even the best correlations of experimental and simulated methyl group Lipari-Szabo generalized order parameters fall below an R(2) of 0.8. PMID- 26990792 TI - Children's understanding of the addition/subtraction complement principle. AB - BACKGROUND: In the last decades, children's understanding of mathematical principles has become an important research topic. Different from the commutativity and inversion principles, only few studies have focused on children's understanding of the addition/subtraction complement principle (if a - b = c, then c + b = a), mainly relying on verbal techniques. AIM: This contribution aimed at deepening our understanding of children's knowledge of the addition/subtraction complement principle, combining verbal and non-verbal techniques. SAMPLE: Participants were 67 third and fourth graders (9- to 10-year olds). METHODS: Children solved two tasks in which verbal reports as well as accuracy and speed data were collected. These two tasks differed only in the order of the problems and the instructions. In the looking-back task, children were told that sometimes the preceding problem might help to answer the next problem. In the baseline task, no helpful preceding items were offered. The looking-back task included 10 trigger-target problem pairs on the complement relation. RESULTS: Children verbally reported looking back on about 40% of all target problems in the looking-back task; the target problems were also solved faster and more accurately than in the baseline task. These results suggest that children used their understanding of the complement principle. The verbal and non verbal data were highly correlated. DISCUSSION: This study complements previous work on children's understanding of mathematical principles by highlighting interindividual differences in 9- to 10-year-olds' understanding of the complement principle and indicating the potential of combining verbal and non verbal techniques to investigate (the acquisition of) this understanding. PMID- 26990791 TI - Domains of quality of life affecting elderly patients with hand osteoarthritis: a qualitative study in the Asian perspective. AB - OBJECTIVES: Hand osteoarthritis (HOA) is common but little is known about how HOA has impact on disability and quality of life (QoL).We aim to identify important domains of concern among participants suffering from symptomatic HOA in Singapore, representing an Asian socio-cultural context. METHODS: A qualitative study using a focus group technique was performed. We ran focus groups stratified by gender, ethnicity and language. Two independent, trained analysts identified relevant categories and assigned codes to text segments through open coding, with discrepancies resolved through consensus. The final lists of domains and subthemes descriptive of QoL were then compared to the following commonly used HOA specific instruments: Functional Index for Hand Osteoarthritis (FIHOA), Score for Assessment and quantification of Chronic Rheumatic Affections of the Hand (SACRAH), Australian/Canadian Hand Osteoarthritis Index (AUSCAN); and Health Assessment Questionnaire (HAQ). RESULTS: Twenty-six patients (23 women, three men; 24 Chinese and two Malay; mean +/- SD age 62.9 +/- 7.5 years) with symptomatic HOA according to the American College of Rheumatology Classification Criteria participated in seven focus groups. Two and five focus groups were conducted in Chinese and English, respectively. The qualitative analysis revealed pain, stiffness and functional disability as the main domains. However, psychological consequences, aesthetic concerns, participation in leisure activities, participation in family roles were important concepts from the focus groups which were not covered by existing instruments. Impact on work productivity by HOA and the unmet health care need is revealed. CONCLUSION: The domains of concepts important to people with HOA in an Asian socio-cultural context are not fully represented in the most commonly used instruments. Further studies on the selection of main domains relevant to HOA patients are necessary. PMID- 26990793 TI - Body mass index, fat free mass, uric acid, and renal function as blood pressure levels determinants in young adults. AB - AIM: We assessed some major determinants of blood pressure (BP) in young adulthood to plan a lifestyle changes policy METHODS: A cross sectional survey was held, involving 2373 high school people (age 18-21), measuring BP, body mass index (BMI), waist circumference (WCirc), fat free mass (FFM); alcohol and smoking habits were evaluated by a questionnaire. In a subset of this population (n = 60) uric acid (UA), estimated glomerular filtration rate (eGFR) were also evaluated. RESULTS: Smoking and not alcohol was correlated to systolic blood pressure (SBP) through quartiles (31.7%, 39.1%, 46.5%, 45.5%). Systolic BP was significantly correlated with FFM in the whole population (r = 0.51) as well as in SBP quartiles (r = 0.243, 0.138, 0.118, 0.204). FFM-SBP cluster analysis gave two centroids corresponding to sexes; females n = 998; coordinates (116.4 mmHg, 38.9 kg) and males n = 1068; coordinates (131.3 mmHg, 56.7 kg). In the n = 60 substudy a multiple linear regression model (multiple R = 0.741) with SBP as dependent variable and UA, FFM, BMI, eGFR as explicative ones, only UA (beta coefficent = 0.363, partial r = 0.240, P < 0.01) was the determinant of BP particularly in men. Moreover in the same group we found an inverse relationship between eGFR (albeit always in the normal range) and UA, as well as for women (r = -0.54, P < 0.01) and men (r = -0.43, P < 0.01) analyzed separately. CONCLUSIONS: A significant correlation exists between BP and FFM; UA has proven to be the most important SBP determinant. At variance with paediatric age UA was negatively correlated with renal function. Dietary intervention on UA and alcohol habits in young adults seems advisable to prevent hypertension. PMID- 26990794 TI - Pathways to romantic relational aggression through adolescent peer aggression and heavy episodic drinking. AB - Adolescent peer aggression is a well-established correlate of romantic relational aggression; however, the mechanisms underlying this association are unclear. Heavy episodic drinking (or "binge" alcohol use) was examined as both a prior and concurrent mediator of this link in a sample of 282 12-18 year old interviewed four times over 6 years. Path analyses indicated that early peer relational and physical aggression each uniquely predicted later romantic relational aggression. Concurrent heavy episodic drinking fully mediated this effect for peer physical aggression only. These findings highlight two important mechanisms by which peer aggression may increase the risk of later romantic relational aggression: a direct pathway from peer relational aggression to romantic relational aggression and an indirect pathway through peer physical aggression and concurrent heavy episodic drinking. Prevention programs targeting romantic relational aggression in adolescence and young adulthood may benefit from interventions that target multiple domains of risky behavior, including the heavy concurrent use of alcohol. Aggr. Behav. 42:563-576, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990795 TI - Health Disparities and Delayed Health care among Older Adults in California: A Perspective from Race, Ethnicity, and Immigration. AB - OBJECTIVES: To examine racial/ethnic/immigration disparities in health and to investigate the relationships among race/ethnic/immigration status, delayed health care, and health of the elderly. DESIGN AND SAMPLE: Responses from 13,508 people aged 65 and above were analyzed based on the California Health Interview Survey (CHIS) 2011-2012. MEASURES: Key variables include race/ethnicity/immigration status, health outcome, and delayed health care. Age, gender, education, work status, and annual family income are used as covariates. RESULTS: The findings indicate that Whites (regardless of country of birth) and U.S.-born Asians enjoy better health than Latinos, African-Americans, and Foreign born Asians. Foreign-born Asians and foreign-born Latinos have the poorest self reported health and mental health, respectively. Delayed use of health care is negatively associated with both self-reported health and mental health status. CONCLUSIONS: Health disparities exist among older adult populations; the combined effects of minority and immigrant status can be approximated from the results in this study. Health care accessibility and the quality of care should be promoted in minority/immigrant populations. Public health nurses have a strong potential to aide in reducing health disparities among an aging American population that continues to exhibit increasing racial/ethnic diversity. PMID- 26990797 TI - Suppression of lethal-7b and miR-125a/b Maturation by Lin28b Enables Maintenance of Stem Cell Properties in Hepatoblasts. AB - In liver development, hepatoblasts that act as hepatic stem/progenitor cells proliferate and differentiate into both hepatocytes and cholangiocytes to form liver tissues. Although numerous factors contribute to this event, little is known about the roles of microRNAs in hepatoblast proliferation and differentiation. In this study, we focused on the lineage-28 (Lin28) family proteins, which are required for microRNA regulation in pluripotent stem cells and cancer cells, and investigated their roles as regulatory factors for the properties of hepatoblasts. CONCLUSION: Lin28b was specifically expressed in hepatoblasts, and its suppression induced growth arrest and cholangiocyte differentiation of hepatoblasts; mechanistically, Lin28b positively regulates the expression of Lin28b itself and cell cycle-related proteins in hepatoblasts by suppressing the maturation of target microRNAs, lethal-7b and miR-125a/b, enabling maintenance of the stem cell properties of hepatoblasts, such as their capabilities for proliferation and bi-lineage differentiation, during liver development. (Hepatology 2016;64:245-260). PMID- 26990799 TI - Evaluation of B-lines in Patients with Isolated Right Heart Failure. PMID- 26990798 TI - Dating placentalia: Morphological clocks fail to close the molecular fossil gap. AB - Dating the origin of Placentalia has been a contentious issue for biologists and paleontologists. Although it is likely that crown-group placentals originated in the Late Cretaceous, nearly all molecular clock estimates point to a deeper Cretaceous origin. An approach with the potential to reconcile this discrepancy could be the application of a morphological clock. This would permit the direct incorporation of fossil data in node dating, and would break long internal branches of the tree, so leading to improved estimates of node ages. Here, we use a large morphological dataset and the tip-calibration approach of MrBayes. We find that the estimated date for the origin of crown mammals is much older, ~130 145 million years ago (Ma), than fossil and molecular clock data (~80-90 Ma). Our results suggest that tip calibration may result in estimated dates that are more ancient than those obtained from other sources of data. This can be partially overcome by constraining the ages of internal nodes on the tree; however, when this was applied to our dataset, the estimated dates were still substantially more ancient than expected. We recommend that results obtained using tip calibration, and possibly morphological dating more generally, should be treated with caution. PMID- 26990796 TI - The abiotic and biotic drivers of rapid diversification in Andean bellflowers (Campanulaceae). AB - The tropical Andes of South America, the world's richest biodiversity hotspot, are home to many rapid radiations. While geological, climatic, and ecological processes collectively explain such radiations, their relative contributions are seldom examined within a single clade. We explore the contribution of these factors by applying a series of diversification models that incorporate mountain building, climate change, and trait evolution to the first dated phylogeny of Andean bellflowers (Campanulaceae: Lobelioideae). Our framework is novel for its direct incorporation of geological data on Andean uplift into a macroevolutionary model. We show that speciation and extinction are differentially influenced by abiotic factors: speciation rates rose concurrently with Andean elevation, while extinction rates decreased during global cooling. Pollination syndrome and fruit type, both biotic traits known to facilitate mutualisms, played an additional role in driving diversification. These abiotic and biotic factors resulted in one of the fastest radiations reported to date: the centropogonids, whose 550 species arose in the last 5 million yr. Our study represents a significant advance in our understanding of plant evolution in Andean cloud forests. It further highlights the power of combining phylogenetic and Earth science models to explore the interplay of geology, climate, and ecology in generating the world's biodiversity. PMID- 26990800 TI - Analytical Evaluation of Free Testosterone and Cortisol Immunoassays in Saliva as a Reliable Alternative to Serum in Sports Medicine. AB - BACKGROUND: This study was aimed to investigate whether measurement of free testosterone and cortisol in saliva is a reliable alternative to their assessment in serum for monitoring physical fitness in professional athletes. METHODS: We studied 25 members of the soccer team Parma F.C., playing in Italian major football league. Blood and saliva samples were collected at fasting, before a regular training session. Cortisol, total and free testosterone, as well as the ratio between free testosterone and cortisol, were assessed in paired serum and saliva samples, and their results were compared. RESULTS: An excellent correlation was found between serum and saliva cortisol (r = 0.751; P < 0.001). A significant correlation was also observed between free testosterone in serum and saliva (r = 0.590; P = 0.002), whereas no significant correlation was found between total testosterone in serum and saliva (r = 0.181; P = 0.387). A significant correlation was found for the free testosterone to cortisol ratio in serum and saliva (r = 0.43; P = 0.031). All athletes (25/25; 100%) declared that they would feel more comfortable to have saliva rather than blood serially collected. CONCLUSIONS: The results of this study suggest that measurement of free testosterone and cortisol in saliva may be seen as a reliable alternative to their assessment in serum. PMID- 26990801 TI - Muscarinic control of rostromedial tegmental nucleus GABA neurons and morphine induced locomotion. AB - Opioids induce rewarding and locomotor effects by inhibiting rostromedial tegmental GABA neurons that express MU-opioid and nociceptin receptors. These GABA neurons then strongly inhibit dopamine neurons. Opioid-induced reward, locomotion and dopamine release also depend on pedunculopontine and laterodorsal tegmental cholinergic and glutamate neurons, many of which project to and activate ventral tegmental area dopamine neurons. Here we show that laterodorsal tegmental and pedunculopontine cholinergic neurons project to both rostromedial tegmental nucleus and ventral tegmental area, and that M4 muscarinic receptors are co-localized with MU-opioid receptors associated with rostromedial tegmental GABA neurons. To inhibit or excite rostromedial tegmental GABA neurons, we utilized adeno-associated viral vectors and DREADDs to express designed muscarinic receptors (M4D or M3D respectively) in GAD2::Cre mice. In M4D expressing mice, clozapine-N-oxide increased morphine-induced, but not vehicle induced, locomotion. In M3D-expressing mice, clozapine-N-oxide blocked morphine induced, but not vehicle-induced, locomotion. We propose that cholinergic inhibition of rostromedial tegmental GABA neurons via M4 muscarinic receptors facilitates opioid inhibition of the same neurons. This model explains how mesopontine cholinergic systems and muscarinic receptors in the rostromedial tegmental nucleus and ventral tegmental area are important for dopamine-dependent and dopamine-independent opioid-induced rewards and locomotion. PMID- 26990802 TI - Effect of diesel exhaust particles on renal vascular responses in rats with chronic kidney disease. AB - Several recent studies have indicated the possible association between exposure to particulate air pollution and the increased rate of morbidity and mortality in patients with kidney diseases. The link of this observation to vascular damage has not been adequately addressed. Therefore, this study aims to investigate possible vascular damage that might be associated with exposure to diesel exhaust particles (DP) in adenine (AD)-induced chronic kidney disease (CKD) in rats, and the possible ameliorative effect of gum acacia (GA). CKD was induced by feeding AD (0.75%, w/w), and DP (0.5 mg/kg) was instilled intratracheally every second day and GA was given concomitantly in the drinking water at a dose of 15% w/v. All treatments were given concomitantly for 28 days. Changes in renal blood flow (RBF) and systolic and diastolic blood pressure were monitored in these animals after anesthesia, together with several other endpoints. Exposure to DP significantly reduced RBF and this was significantly potentiated in AD-treated rats. Phenylephrine-induced decreases in RBF and increases in systolic and diastolic blood pressure were severely potentiated in rats exposed to DP, and these actions were significantly augmented in AD-treated rats. GA did not significantly affect the vascular impairment induced by AD and DP given together. This study provides experimental evidence that exposure to particulate air pollution can exacerbate the vascular damage seen in patients with CKD. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 541-549, 2017. PMID- 26990803 TI - Concepts of Mental Disorders in Trainee Clinical Psychologists. AB - BACKGROUND: The models of mental disorders held by all mental health professionals are implicit in their attitudes and inform all aspects of theory and practice. The present study aims to explore the attitudes of trainee clinical psychologists towards mental disorders by building on a study conducted by Harland et al. () with psychiatrists. In so doing, the present study contributes to an evidence base that can inform the development of clinical training programs and multidisciplinary working. METHODS: The Maudsley Attitude Questionnaire was administered in an online survey of trainee clinical psychologists (n = 289). RESULTS: Analyses of variance revealed main effects of model, and of diagnostic category, and a significant interaction effect between model and diagnostic category. Principal component analysis revealed a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. Comparisons with Harland et al.'s () psychiatrists revealed large differences, particularly in biological and social constructionist model endorsement. CONCLUSION: Results suggest that the attitudes of psychologists and psychiatrists continue to sit at opposite ends of a biological-psychosocial continuum. However, an area of consensus regarding psychotherapeutic models was indicated. Training courses can be reassured that strong opinions tended to reflect the evidence base. Future research with similarly large representative samples from different disciplines would allow findings of the current study to be better contextualized. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: The models of mental disorders held by clinical psychologists are implicit in their attitudes and inform all aspects of theory and practice. We found that trainee clinical psychologists continue to favour psychosocial over biological understandings of mental disorders, giving the cognitive, behavioural and psychodynamic models equal value overall, and stronger attitudes were supported by the evidence base. We found that trainee clinical psychologists organized their attitudes around a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. These findings may be useful for those involved in developing clinical training programs and multidisciplinary working because they provide an insight into the attitudes of emerging clinical psychologists. PMID- 26990804 TI - Influences on preschool children's oral health-related quality of life as reported by English and Spanish-speaking parents and caregivers. AB - OBJECTIVE: This study examined young, preschool children's oral health-related quality of life (OHRQoL) among a community-based cohort of English and Spanish speaking parent-child dyads in North Carolina, and sought to quantify the association of parent/caregiver characteristics, including spoken language, with OHRQoL impacts. METHODS: Data from structured interviews with 1,111 parents of children aged 6-23 months enrolled in the Zero-Out Early Childhood Caries study in 2010-2012 were used. OHRQoL was measured using the overall score (range: 0-52) of the Early Childhood Oral Health Impact Scale (ECOHIS). We examined associations with parents' sociodemographic characteristics, spoken language, self-reported oral and general health, oral health knowledge, children's dental attendance, and dental care needs. Analyses included descriptive, bivariate, and multivariate methods based upon zero-inflated negative binomial regression. To determine differences between English and Spanish speakers, language-stratified model estimates were contrasted using homogeneity chi2 tests. RESULTS: The mean overall ECOHIS score was 3.9 [95% confidence interval (CI) = 3.6-4.2]; 4.7 among English-speakers and 1.5 among Spanish speakers. In multivariate analyses, caregivers' education showed a positive association with OHRQoL impacts among Spanish speakers [prevalence ratio (PR) = 1.12 (95% CI = 1.03-1.22), for every added year of schooling], whereas caregivers' fair/poor oral health showed a positive association among English speakers (PR = 1.20; 95% CI = 1.02-1.41). CONCLUSIONS: The overall severity of ECOHIS impacts was low among this population based sample of young, preschool children, and substantially lower among Spanish versus English speakers. Further studies are warranted to identify sources of these differences in - actual or reported - OHRQoL impacts. PMID- 26990805 TI - Controlled Chemistry Approach to the Oxo-Functionalization of Graphene. AB - Graphene is the best-studied 2D material available. However, its production is still challenging and the quality depends on the preparation procedure. Now, more than a decade after the outstanding experiments conducted on graphene, the most successful wet-chemical approach to graphene and functionalized graphene is based on the oxidation of graphite. Graphene oxide has been known for more than a century; however, the structure bears variable large amounts of lattice defects that render the development of a controlled chemistry impossible. The controlled oxo-functionalization of graphene avoids the formation of defects within the sigma-framework of carbon atoms, making the synthesis of specific molecular architectures possible. The scope of this review is to introduce the field of oxo functionalizing graphene. In particular, the differences between GO and oxo functionalized graphene are described in detail. Moreover analytical methods that allow determining lattice defects and functional groups are introduced followed by summarizing the current state of controlled oxo-functionalization of graphene. PMID- 26990807 TI - Inflammatory bowel disease in the clinic: Escalation and de-escalation of therapy: A longitudinal case-based discussion. PMID- 26990806 TI - Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent Protein-Ligand Interactions. AB - A highly efficient cap-exchange approach for preparing compact, dense polyvalent mannose-capped quantum dots (QDs) has been developed. The resulting QDs have been successfully used to probe multivalent interactions of HIV/Ebola receptors DC SIGN and DC-SIGNR (collectively termed as DC-SIGN/R) using a sensitive, ratiometric Forster resonance energy transfer (FRET) assay. The QD probes specifically bind DC-SIGN, but not its closely related receptor DC-SIGNR, which is further confirmed by its specific blocking of DC-SIGN engagement with the Ebola virus glycoprotein. Tuning the QD surface mannose valency reveals that DC SIGN binds more efficiently to densely packed mannosides. A FRET-based thermodynamic study reveals that the binding is enthalpy-driven. This work establishes QD FRET as a rapid, sensitive technique for probing structure and thermodynamics of multivalent protein-ligand interactions. PMID- 26990808 TI - Undergraduate nursing students' attitudes and use of research and evidence-based practice - an integrative literature review. AB - AIMS AND OBJECTIVES: This integrative review of the literature addresses undergraduate nursing students' attitudes towards and use of research and evidence-based practice, and factors influencing this. Current use of research and evidence within practice, and the influences and perceptions of students in using these tools in the clinical setting are explored. BACKGROUND: Evidence based practice is an increasingly critical aspect of quality health care delivery, with nurses requiring skills in sourcing relevant information to guide the care they provide. Yet, barriers to engaging in evidence-based practice remain. To increase nurses' use of evidence-based practice within healthcare settings, the concepts and skills required must be introduced early in their career. To date, however, there is little evidence to show if and how this inclusion makes a difference. DESIGN: Integrative literature review. METHODS: ProQuest, Summon, Science Direct, Ovid, CIAP, Google scholar and SAGE databases were searched, and Snowball search strategies used. One hundred and eighty-one articles were reviewed. Articles were then discarded for irrelevance. Nine articles discussed student attitudes and utilisation of research and evidence based practice. RESULTS: Factors surrounding the attitudes and use of research and evidence-based practice were identified, and included the students' capability beliefs, the students' attitudes, and the attitudes and support capabilities of wards/preceptors. CONCLUSIONS: Undergraduate nursing students are generally positive toward using research for evidence-based practice, but experience a lack of support and opportunity. These students face cultural and attitudinal disadvantage, and lack confidence to practice independently. Further research and collaboration between educational facilities and clinical settings may improve utilisation. RELEVANCE TO CLINICAL PRACTICE: This paper adds further discussion to the topic from the perspective of and including influences surrounding undergraduate students and new graduate nurses. PMID- 26990809 TI - The role of collaboration in the cognitive development of young children: a systematic review. AB - BACKGROUND: Collaboration is a key facilitator of cognitive development in early childhood; this review evaluates which factors mediate the impact of collaborative interactions on cognitive development in children aged 4-7 years. METHODS: A systematic search strategy identified relevant studies (n = 21), which assessed the role of ability on the relationship between collaboration and cognitive development. Other factors that interact with ability were also assessed: gender, sociability/friendship, discussion, age, feedback and structure. RESULTS: Immediate benefits of collaboration on cognitive development are highlighted for same-age peers. Collaborative interactions are beneficial for tasks measuring visual perception, problem-solving and rule-based thinking, but not for word-reading and spatial perspective-taking. Collaboration is particularly beneficial for lower-ability children when there is an ability asymmetry. High-ability children either regressed or did not benefit when paired with lower-ability participants. CONCLUSIONS: Overall, the studies included within this review indicate that brief one-off interactions can have a significant, positive effect on short-term cognitive development in children of infant school age. The longer-term advantages of collaboration are still unclear. Implications for practice and future research are discussed. PMID- 26990810 TI - Automation for clinical CD4 T-cell enumeration, a desirable tool in the hands of skilled operators. AB - BACKGROUND: Automation in HIV clinical flow cytometry when appropriately applied brings considerable standardisation benefits. The Canadian Immunology Quality Assessment Program (CIQAP) detected situations where operators did not manually override automated software in the event of improper output on the Epics XL and FC500 CD4 immunophenotyping platforms. The automated gating algorithm identifies lymphocytes using a double gate strategy based on CD45 * side scatter (SS) gating and a light scatter FS * SS gate known to fail with sub optimal specimens. METHOD: To generate correct interpretation and results CIQAP introduced a simple protocol modification, bypassing the light scatter gate to include all cells characterized by the CD45 gate. Seventeen problem cases were reanalysed for both absolute and relative T-cell subsets accuracy and compared to the CIQAP group mean values. Results were found to be associated with the percentage of lymphocytes excluded by the automated light scatter gate. RESULTS: The modified manual protocol resolved poor performance in 14 instances out of 17 problem cases. It was found to improve accuracy when the light scatter gate excluded greater than 5% of the cells. The remaining three cases had a lymphocyte recovery of greater than 94.6% in the original automated analysis. CONCLUSION: There is a risk in relying solely on automated gating procedures when using the Epics XL and FC500 CD4 immunophenotyping platforms. Laboratory managers have the responsibility to intervene when required. EQA providers are equally responsible to alert the clinical laboratories of the need to update operator training to deal with stressed specimens. (c) 2016 International Clinical Cytometry Society. PMID- 26990811 TI - Overexpression of the truncated version of ILV2 enhances glycerol production in Saccharomyces cerevisiae. AB - Acetolactate synthase is a mitochondrial enzyme that catalyses the conversion of two pyruvate molecules to an acetolactate molecule with release of carbon dioxide. The overexpression of the truncated version of the corresponding gene, ILV2, that codes for presumably cytosolic acetolactate synthase in the yeast Saccharomyces cerevisiae, led to a decrease in intracellular pyruvate concentration. This recombinant strain was also characterized by a four-fold increase in glycerol production, with a concomitant 1.8-fold reduction in ethanol production, when compared to that of the wild-type strain under anaerobic conditions in a glucose alcoholic fermentation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990812 TI - Histiocytic sarcoma as a secondary malignancy: pathobiology, diagnosis, and treatment. AB - Histiocytic sarcoma (HS) is an extremely rare non-Langerhans cell disorder with an aggressive course and limited treatment options. Recent advances in molecular/genetic sequencing have suggested a common clonal origin between various hematolymphoid disorders and cases of secondary HS. Deriving conclusions from previously reported cases of HS arising secondarily to certain hematolymphoid disorders, here we have tried to provide insight into the mechanisms influencing this evolution. We also discuss a clinical case of a 72 year-old man with a diagnosis of chronic myeloid leukemia (CML), presenting subsequently with a heterogeneous liver mass positive with a diagnosis of HS. The liver mass showed a retained BCR-ABL1 translocation suggesting clonality between the CML and HS. As seen in our case and other reported cases of HS derived secondarily, the concurrent expression of immunoglobulin heavy (IGH)-/light-chain rearrangements or cytogenetic markers common to the primary malignancy suggests an evolutionary mechanism involving lineage switching that could potentially be influenced by genetic or epigenetic cues which may occur at the level of a progenitor or the malignant cell itself. PMID- 26990813 TI - Simultaneous analysis of ten phytohormones in Sargassum horneri by high performance liquid chromatography with electrospray ionization tandem mass spectrometry. AB - Phytohormones have attracted wide attention due to their important biological functions. However, their detection is still a challenge because of their complex composition, low abundance and diverse sources. In this study, a novel method of high-performance liquid chromatography with electrospray ionization tandem mass spectrometry was developed and validated for the simultaneous determination of ten phytohormones including indole-3-acetic acid, isopentenyladenine, isopentenyl adenosine, trans-zeatin riboside, zeatin, strigolactones, abscisic acid, salicylic acid, gibberellin A3, and jasmonic acid in Sargassum horneri (S. horneri). The phytohormones were extracted from freeze-dried S. horneri with methanol/water/methanoic acid (15:4:1, v/v/v) analyzed on a Hypersil Gold C18 column and detected by electrospray ionization tandem triple quadrupole mass spectrometry in the multiple reaction monitoring mode. The experimental conditions for the extraction and analysis of phytohormones were optimized and validated in terms of reproducibility, linearity, sensitivity, recovery, accuracy, and stability. Distributions of the phytohormones in the stems, blades, and gas bladder of the S. horneri in drift, fixed, and semi-fixed growing states were investigated for the first time. The observed contents of the phytohormones in S. horneri range from not detected to 5066.67 ng/g (fresh weight). Most phytohormones are distributed mainly in the stems of S. horneri in drift and semi fixed states. PMID- 26990814 TI - Translating colorectal cancer genetics into clinically useful biomarkers. AB - Colorectal cancer (CRC) is a major health problem worldwide accounting for over a million deaths annually. While many patients with Stage II and III CRC can be cured with combinations of surgery, radiotherapy and chemotherapy, this is morbid costly treatment and a significant proportion will suffer recurrence and eventually die of CRC. Increased understanding of the molecular pathogenesis of CRC has the potential to identify high risk patients and target therapy more appropriately. Despite increased understanding of the molecular events underlying CRC development, established molecular techniques have only produced a limited number of biomarkers suitable for use in routine clinical practice to predict risk, prognosis and response to treatment. Recent rapid technological developments, however, have made genomic sequencing of CRC more economical and efficient, creating potential for the discovery of genetic biomarkers that have greater diagnostic, prognostic and therapeutic capabilities for the management of CRC. This paper reviews the current understanding of the molecular pathogenesis of CRC, and summarizes molecular biomarkers that surgeons will encounter in current clinical use as well as those under development in clinical and preclinical trials. New molecular technologies are reviewed together with their potential impact on the understanding of the molecular pathogenesis of CRC and their potential clinical utility in classification, diagnosis, prognosis and targeting of therapy. PMID- 26990815 TI - Repair of rat critical size calvarial defect using osteoblast-like and umbilical vein endothelial cells seeded in gelatin/hydroxyapatite scaffolds. AB - The present study used a previously developed three-dimensional Gelatin/Hydroxyapatite (Gel/HA) homogeneous nanocomposite scaffold with porosity of 82% and interconnecting pores ranging from 300 to 500 MUm. Cell-seeded scaffolds were used to evaluate bone regeneration of rat critical-size calvarial defect. Totally, 36 male Wistar rats were randomly divided into four experimental groups, including blank defect (defects without any graft), blank scaffold (defects filled with Gel/HA scaffold without cells), and two groups of cell seeded scaffolds (defects filled with either Gel/HA scaffold seeded with osteoblast-like and endothelial cells or osteoblast-like cell-seeded constructs). After 1, 4, and 12 weeks of scaffold implantation, rats were sacrificed and the calvaria were harvested for histological, immunohistochemical and histomorphometric analysis. In vitro tests showed that scaffolds were nontoxic to cells and promoted ideal cellular attachment. In vivo investigation on scaffold revealed that blank calvarial defects indicated incomplete tissue coverage and little evidence of bone healing. However, blank scaffold and cell-seeded scaffolds significantly promoted osteoconduction and ostegogenesis. Taken together, pre-seeded Gel/HA nanocomposite scaffold with osteoblasts and endothelial cells presented an effective combination to improve osteogenesis in the engineered bone implant. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1770-1778, 2016. PMID- 26990816 TI - Regeneration of Aqueous Periodate Solutions by Ozone Treatment: A Sustainable Approach for Dialdehyde Cellulose Production. AB - A method for easy and fast regeneration of aqueous periodate solutions from dialdehyde cellulose (DAC) production by ozone treatment is presented, along with a direct and reliable simultaneous quantification of iodate and periodate by reversed-phase HPLC. The influence of iodate and ozone concentration, solution pH, and reaction time on the regeneration efficiency was studied, as well as the reaction kinetics. Regeneration of spent periodate solutions by ozone was successfully performed in alkaline medium, which favors the formation of free (.) OH radicals, as supported by the addition of radical scavengers and quantum mechanical calculations. At pH 13 and an ozone concentration of approximately 150 mg L(-1) , periodate was completely regenerated from a 100 mm solution of iodate within 1 h at room temperature. A cyclic process of cellulose oxidation and subsequent regeneration of spent periodate with 90 % efficiency has been developed. So far, commercial applications of DAC have been hampered by difficulties in reusing the costly periodate. This work overcomes this hurdle and presents a highly efficient, clean, and low-cost protocol for the preparation of DAC with integrated periodate recycling, with the possibility of scaling the process up. PMID- 26990817 TI - Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma. AB - Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. PMID- 26990818 TI - Targeted Synthesis of Two Super-Complex Zeolites with Embedded Isoreticular Structures. AB - A novel structural coding approach combining structure solution, prediction, and the targeted synthesis of new zeolites with expanding complexity and embedded isoreticular structures was recently proposed. Using this approach, the structures of two new zeolites in the RHO family, PST-20 and PST-25, were predicted and synthesized. Herein, by extending this approach, the next two higher generation members of this family, PST-26 and PST-28, have been predicted and synthesized. These two zeolites have much larger unit cell volumes (422,655 A(3) and 614,912 A(3), respectively) than those of the lower generations. Their crystallization was confirmed by a combination of both powder X-ray and electron diffraction techniques. Aluminate and water concentrations in the synthetic mixture were found to be the two most critical factors influencing the structural expansion of embedded isoreticular zeolites under the synthetic conditions studied herein. PMID- 26990819 TI - Insight into the Mechanism of the Michael Reaction. AB - The mechanism for the nucleophilic addition step of the Michael reaction between methanethiol as a model Michael donor and several alpha-substituted methyl acrylates (X=F, Cl, Me, H, CN, NO2 ) as model Michael acceptors is described in detail. We suggest a novel way to condense electrophilic Fukui functions at specific atoms in terms of the contributions from the atomic orbitals to the LUMO or, more generally, to the orbital controlling the reaction. This procedure correctly associates activation energies to local electrophilic Fukui indices for the cases treated in this work. The calculated reaction barriers strongly depend on the nature of the substituent. As a general rule, activation energies are governed by structural changes, although electronic factors are significant for electron-withdrawing groups. Nucleophilic addition to Michael receptors is best described as a highly nonsynchronous process, in which the geometry of the transition state comprises a nonplanar six-membered ring. Formation of the S???C bond, which defines the interaction between the reactants, progresses ahead of all other primitive processes in the early stages of the transformation. In view of our results, we postulate that highly complex chemical reactions, as is the case for the nucleophilic addition step studied herein, that involve cleavage/formation of a total of six bonds, lower their activation energies by favoring nonsynchronicity, that is, for these types of systems, primitive changes should advance at different rates. PMID- 26990820 TI - Changes to nurses' practice environment over time. AB - AIMS: To examine changes in the nursing practice environment, retention-related factors, unit stability and patient care tasks delayed or left undone, over two periods between 2004 and 2013. BACKGROUND: Positive nurse practice environments have been linked to nurse retention and care quality outcomes. METHODS: The collection of the Practice Environment Scale of the Nursing Work Index, job satisfaction, intent to leave, unit instability and tasks delayed or not done at six acute-care hospitals across three Australian states, in two waves between 2004 and 2013; results from the two waves are compared. RESULTS: On average, practice environment scores declined slightly; nurses reported a greater difficulty in finding another nursing position, lower intent to leave their current job and greater instability in their current position. Rates of delayed tasks increased over the period, whereas rates of tasks left undone have decreased over the period. CONCLUSIONS: The decline in nurses' perceptions of the quality of the practice environment is disappointing, particularly given the protracted workforce shortages that have persisted. Significant organisational restructuring and turnover of nurse executives may have contributed to this decline. IMPLICATION FOR NURSING MANAGEMENT: Managers need to apply existing evidence to improve nurse practice environments and manage instability. PMID- 26990821 TI - Long-term excess mortality in takotsubo cardiomyopathy: predictors, causes and clinical consequences. AB - AIMS: Despite increasing research efforts, the prognostic consequences of takotsubo cardiomyopathy (TTC) remain largely unknown. The aim of this study was therefore to compare the long-term mortality rate of TTC patients with high-risk patients presenting with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 286 patients with TTC were matched for age and gender with 286 STEMI patients. Outcome was obtained with a standardized telephone follow-up. The primary analysis determined long-term mortality. A secondary analysis was performed evaluating 28-day and 1-year mortality. Follow up was available for 96% of patients after a mean of 3.8 +/- 2.5 years. In TTC patients, long-term mortality was significantly higher compared with the matched STEMI cohort [24.7% vs. 15.1%, hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.07-2.33; P = 0.02]. There was no significant difference in the rates of 28 day (5.5% vs. 5.7%, HR 0.96, 95% CI 0.47-1.94; P = 0.91) and 1-year mortality (12.5% vs. 9%, HR 1.42, 95% CI 0.85-2.38; P = 0.18). In multivariable regression analysis, male sex, a high Killip class on admission, and diabetes mellitus were identified as independent predictors of mortality in TTC patients. A risk score consisting of these factors showed a higher mortality with an increasing number of risk factors. CONCLUSION: Mortality rates in TTC patients are higher than previously expected and long-term mortality exceeded that of patients with STEMI. A simple risk score may provide an approach to identify high-risk patients and predict clinical prognosis. PMID- 26990823 TI - PrEP Adherence Patterns Strongly Affect Individual HIV Risk and Observed Efficacy in Randomized Clinical Trials. AB - BACKGROUND: Randomized controlled trials (RCTs) suggest that the efficacy of tenofovir-based preexposure prophylaxis (PrEP) strongly depends on the consistency of PrEP use. We explore how the patterns of pill taking and waning of PrEP protection may affect PrEP efficacy for HIV prevention. METHODS: A 2-arm RCT was simulated by mathematical models assuming that the prescribed daily doses were skipped periodically, randomly, or in large blocks. Risk-driven adherence, in which PrEP was taken when sex was expected, was also investigated. Three temporal PrEP protection profiles were explored: long (5 days), intermediate (3 days), and short (24 hours). Modeling results were compared to the efficacy observed in completed RCTs. RESULTS: The expected PrEP efficacy was 60% with periodic, 50% with random, and 34% with block adherence when PrEP had a long protection profile and pills were taken only 50% of the days. Risk-driven pill taking resulted in 29% and 37% daily pills taken and efficacy of 43% and 51%, respectively, for long protection. High PrEP efficacy comparable with that observed in Partners PrEP and Centers for Disease Control and Prevention Botswana trials was simulated under long protection, high overall adherence, and limited block pill taking; the moderate efficacy observed in iPrEx and Bangkok trials was comparable with the 50% adherence scenarios under random pill taking and long protection. CONCLUSIONS: Pill-taking patterns may have a substantial impact on the protection provided by PrEP even when the same numbers of pills are taken. When PrEP retains protection for longer than a day, pill-taking patterns can explain a broad range of efficacies observed in PrEP RCTs. PMID- 26990822 TI - Brief Report: Apparent Antiretroviral Overadherence by Pill Count is Associated With HIV Treatment Failure in Adolescents. AB - Pill counts with calculated adherence percentages are used in many settings to monitor adherence, but can be undermined by patients discarding pills to hide nonadherence. Pill counts suggesting that >100% of prescribed doses were taken can signal "pill dumping." We defined "overadherence" among a cohort of 300 HIV infected adolescents as having greater than one-third of pill counts with >100% adherence during a year of follow-up. Apparent overadherence was more common in those with virologic failure than in those with suppressed viral loads (33% vs 13%, chi(2) P = 0.001). Pill count adherence repeatedly >100% may identify HIV infected adolescents at increased risk of treatment failure. PMID- 26990824 TI - The Effect of Timing of Initiation of Antiretroviral Therapy on Loss to Follow-up in HIV-Tuberculosis Coinfected Patients in South Africa: An Open-Label, Randomized, Controlled Trial. AB - OBJECTIVE: To evaluate the effect of early integrated, late-integrated, and delayed antiretroviral therapy (ART) initiation during tuberculosis (TB) treatment on the incidence rates of loss to follow-up (LTFU) and to evaluate the effect of ART initiation on LTFU rates within trial arms in patients coinfected with TB and HIV. METHODS: A substudy within a 3-armed, open label, randomized, controlled trial. Patients were randomized to initiate ART either early or late during TB treatment or after the TB treatment completion. We reported the incidence and predictors of LTFU from TB treatment initiation during the 24 months of follow-up. LTFU was defined as having missed 4 consecutive monthly visits with the inability to make contact. RESULTS: Of the 642 patients randomized, a total of 96 (15.0%) were LTFU at a median of 6.0 [interquartile range (IQR), 1.1-11.3] months after TB treatment initiation. Incidence rates of LTFU were 7.5 per 100 person-years (PY) [95% confidence interval (CI): 4.9 to 11], 10.9 per 100 PY (95% CI: 7.6 to 15.1), and 11.0 per 100 PY (95% CI: 7.6 to 15.4) in the early integrated, late-integrated, and delayed treatment arms (P = 0.313). Incidence rate of LTFU before and after ART initiation was 31.7 per 100 PY (95% CI: 11.6 to 69.0) vs. 6.1 per 100 PY (95% CI: 3.7 to 9.4); incidence rate ratio (IRR) was 5.2 (95% CI: 2.1 to 13.0; P < 0.001) in the early integrated arm; 31.9 per 100 PY (95% CI: 20.4 to 47.5) vs. 4.7 per 10 PY (95% CI: 2.4 to 8.2) and IRR was 6.8 (95% CI: 3.4 to 13.6; P < 0.0001) in the late-integrated arm; and 21.9 per 100 PY (95% CI: 14.6 to 31.5) vs. 2.8 per 100 PY (95% CI: 0.9 to 6.6) and IRR was 7.7 (95% CI: 3.0 to 19.9; P < 0.0001) in the sequential arm. CONCLUSION: LTFU rates were not significantly different between the 3 trials arms. However, ART initiation within each trial arm resulted in a significant reduction in LTFU rates among TB patients. PMID- 26990825 TI - High Variability of Hormonal Levels and No Clinically Relevant Interaction Between Ethinyl Estradiol, Desogestrel and Lopinavir/Ritonavir in a Small Sample of HIV-positive Adolescents. AB - BACKGROUND: We report the pharmacokinetic interactions of combined oral contraceptive (COC) containing ethinyl estradiol (EE2)/desogestrel (DSG) with lopinavir/ritonavir (LPV/r) in 16 HIV-positive adolescents. METHODS: We measured Ctrough of EE2 and etonogestrel (ENG), the active metabolite of DSG, in HIV positives on LPV/r-based ART; Ctrough of LPV/r with and without COC; endogenous progesterone. EE2/ENG levels were compared with our own historical data of HIV negative controls. RESULTS: Ctrough of EE2 and ENG varied from 3 to 57 pg/mL and from 1051 to 5000 pg/mL, respectively. The geometric mean ratios (GMR) of Ctrough in HIV-positives on LPV/r with COC versus HIV-negative controls with COC only were 0.68 (95% CI: 0.42 to 1.08) or 32% decreased (P = 0.10) for EE2; and 1.08 (95% CI: 0.73 to 1.60) or 8% increased (P = 0.68) for ENG. Endogenous progesterone was <1.0 ng/mL in all participants, consistent with anovulation. Ctrough of LPV decreased statistically insignificantly with COC and remained above the desired therapeutic minimum of 1.0 mg/L in all. CONCLUSIONS: The study found no clinically relevant interaction between EE2/DSG and LPV/r. This was supported by suppressed ovulation, assessed by low endogenous progesterone levels in all participants; and preserved antiretroviral activity, assessed by LPV/r levels above the desired therapeutic minimum in all participants. However, the high variability of hormonal levels warrants individual monitoring and further investigation. Condom use should always be encouraged for infection prevention. PMID- 26990827 TI - Sindbis virus as a human pathogen-epidemiology, clinical picture and pathogenesis. AB - Sindbis virus (SINV; family Togaviridae, genus Alphavirus) is an enveloped RNA virus widely distributed in Eurasia, Africa, Oceania and Australia. SINV is transmitted among its natural bird hosts via mosquitoes. Human disease caused by SINV infection has been reported mainly in South Africa and in Northern Europe. Vector mosquito abundance affects the annual incidence of SINV infections with occasional outbreaks of up to 1500 patients. Symptoms include fever, malaise, rash and musculoskeletal pain. In a significant portion of patients the debilitating musculoskeletal symptoms persist for years. Chronic disease after SINV infection shares many features with autoimmune diseases. Currently there is no specific treatment available. Recently SINV infections have been detected outside the previously known distribution range. In this article we will summarize the current knowledge on epidemiology, clinical disease and pathogenesis of SINV infection in man. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990826 TI - Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis. AB - BACKGROUND: Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression. METHODS: We determined the incidence and predictors of advanced hepatic fibrosis measured by the Fibrosis-4 index (>=3.25) in a large diverse population of HIV-infected patients without significant liver disease at baseline (Fibrosis-4 score <1.45) in care between January 2000 and March 2014. We used Cox proportional hazards analysis to examine factors associated with progression to Fibrosis-4 score >=3.25. RESULTS: Among 14,198 HIV-infected patients, hepatitis C virus (HCV) coinfection [adjusted hazard ratio (aHR) 1.9, 95% confidence interval (CI): 1.6 to 2.1], hepatitis B virus coinfection (aHR 1.5, 95% CI: 1.2 to 1.8), alcohol-use disorder (aHR 1.4, 95% CI: 1.2 to 1.6), and diabetes (aHR 1.9, 95% CI: 1.6 to 2.3) were associated with progression to advanced fibrosis in multivariable analysis. In addition, patients at each lower level of time-varying CD4 cell count had a significantly greater risk of progression, with ~7-fold higher risk in those with CD4 <100 cells per cubic millimeter (aHR 6.9, 95% CI: 5.8 to 8.3) compared with CD4 >=500 cells per cubic millimeter. An increasing gradient of risk was also observed among patients with higher time-varying HIV viral load (VL), with the greatest risk noted with VL >=100,000 copies per milliliter (aHR 2.6, 95% CI: 2.2 to 3.1) compared with VL <500 copies per milliliter. CONCLUSIONS: Lower CD4 cell count and higher HIV VL were significantly associated with progression to advanced hepatic fibrosis in a dose-dependent manner, independent of the risk associated with traditional factors: hepatitis C virus or hepatitis B virus coinfection, alcohol, and diabetes. Our findings suggest that early treatment of HIV infection could mitigate liver disease. PMID- 26990828 TI - Hereditary non-polyposis colorectal cancer/Lynch syndrome in three dimensions. AB - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. METHODS: Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. RESULTS: There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. CONCLUSION: Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance. PMID- 26990829 TI - Rapamycin Interferes With Postdepletion Regulatory T Cell Homeostasis and Enhances DSA Formation Corrected by CTLA4-Ig. AB - Previously, we demonstrated that alemtuzumab induction with rapamycin as sole maintenance therapy is associated with an increased incidence of humoral rejection in human kidney transplant patients. To investigate the role of rapamycin in posttransplant humoral responses after T cell depletion, fully MHC mismatched hearts were transplanted into hCD52Tg mice, followed by alemtuzumab treatment with or without a short course of rapamycin. While untreated hCD52Tg recipients acutely rejected B6 hearts (n = 12), hCD52Tg recipients treated with alemtuzumab alone or in conjunction with rapamycin showed a lack of acute rejection (MST > 100). However, additional rapamycin showed a reduced beating quality over time and increased incidence of vasculopathy. Furthermore, rapamycin supplementation showed an increased serum donor-specific antibodies (DSA) level compared to alemtuzumab alone at postoperation days 50 and 100. Surprisingly, additional rapamycin treatment significantly reduced CD4(+) CD25(+) FoxP3(+) T reg cell numbers during treatment. On the contrary, ICOS(+) PD-1(+) CD4 follicular helper T cells in the lymph nodes were significantly increased. Interestingly, CTLA4-Ig supplementation in conjunction with rapamycin corrected rapamycin-induced accelerated posttransplant humoral response by directly modulating Tfh cells but not Treg cells. This suggests that rapamycin after T cell depletion could affect Treg cells leading to an increase of Tfh cells and DSA production that can be reversed by CTLA4-Ig. PMID- 26990830 TI - Biased and unbiased estimation in longitudinal studies with informative visit processes. AB - The availability of data in longitudinal studies is often driven by features of the characteristics being studied. For example, clinical databases are increasingly being used for research to address longitudinal questions. Because visit times in such data are often driven by patient characteristics that may be related to the outcome being studied, the danger is that this will result in biased estimation compared to designed, prospective studies. We study longitudinal data that follow a generalized linear mixed model and use a log link to relate an informative visit process to random effects in the mixed model. This device allows us to elucidate which parameters are biased under the informative visit process and to what degree. We show that the informative visit process can badly bias estimators of parameters of covariates associated with the random effects, while allowing consistent estimation of other parameters. PMID- 26990831 TI - Partial autolysis of MU/m-calpain during post mortem aging of chicken muscle. AB - The objective of this study was to investigate changes occurring in MU/m-calpain in post mortem chicken muscles and to determine the origin of the unknown bands found in calpain casein zymography. The unknown bands were reported with slightly greater mobility compared to conventional MU/m-calpain bands in casein zymography. Identification of these bands was accomplished using native polyacrylamide gel electrophoresis, liquid chromatography tandem mass spectrometry and with protein phosphatase treatment. Results showed that the unknown bands were corresponding to MU/m-calpain, and dephosphorylation by protein phosphatase did not change their appearance. The calpain samples were then incubated with various concentrations of Ca2+ to determine the relationship between changes in MU/m-calpain and the appearance of the unknown bands. The products of MU/m-calpain partial autolysis were found to be consistent with the appearance of the unknown bands. Therefore, the appearance of these bands did not result from phosphorylation of MU/m-calpain as previously hypothesized, but from partial autolysis of MU/m-calpain. Also their presence suggests that MU/m-calpain undergoes partial autolysis during aging which may play certain roles in meat quality improvement. PMID- 26990832 TI - Two-Dimensional, but not Flat: An All-Boron Graphene with a Corrugated Structure. AB - The construction of single-atom-thick sheets of boron on a silver substrate, which was published in late 2015, represents a significant advance towards the realization of useful two-dimensional materials based solely on boron. This Highlight provides background information on the topic of boron allotropes and an outlook for further work in this area. PMID- 26990834 TI - A Synthesis of 1H-Indazoles via a Cu(OAc)2-Catalyzed N-N Bond Formation. AB - A facile synthesis of 1H-indazoles featuring a Cu(OAc)2-catalyzed N-N bond formation using oxygen as the terminal oxidant is described. The reaction of readily available 2-aminobenzonitriles with various organometallic reagents led to o-aminoaryl N-H ketimine species. The subsequent Cu(OAc)2-catalyzed N-N bond formation in DMSO under oxygen afforded a wide variety of 1H-indazoles in good to excellent yields. PMID- 26990833 TI - Indirect Detection of Glycosidases Using Amperometry. AB - Glycosidases are essential enzymes that cleave glycoside bonds. The presence of glycosidases have been widely used to detect pathogens, label cells/tissues, and report specific diseases. We have developed a rapid electrochemical assay to detect glycosidases. Exposure of electrochemically inactive substrates to glycosidases releases glucose, which can be measured easily using an electrochemical cell. Five different glycosidases were detected rapidly within 1 h using disposable electrodes. This assay could readily be incorporated into repurposed glucose meters to rapidly detect glycosidases, which in turn could be useful to report the presence of a pathogen or illness. PMID- 26990835 TI - [Swallowing Disorders]. AB - Swallowing disorders are a common disease in all ages. The spectrum of diseases in patients with swallowing disorders has significantly changed in the last decades. Often complexe clinical pictures require a multidisciplinary approach including various different professionals. Videofluoroscopy is the method of choice for evaluation of the entire swallowing tract within one investigation. Functional as well as morphological changes can be diagnosed and as a therapeutic study, it helps guide decisions regarding further swallow therapy based on those findings. PMID- 26990836 TI - Standardized terminology and nomenclature for respiratory cytology: The Papanicolaou Society of Cytopathology guidelines. AB - BACKGROUND: The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for cytologic testing, techniques for cytologic sampling, terminology and nomenclature for respiratory diseases, ancillary testing, and recommendations for postcytologic diagnosis follow-up and management. METHODS: All documents are based on the expertise of the authors, an extensive literature review and discussions of the draft documents at national and international meetings over a 12-month period. This document selectively presents the results of these discussions and reports a proposed standardized terminology scheme for respiratory cytology that correlates cytologic diagnosis with biologic behavior and patient management. RESULTS: The classification and terminology scheme recommends a six-tiered system composed of: nondiagnostic, negative, atypical, neoplastic (benign and neoplasms of low malignant potential), suspicious, and positive for malignancy. CONCLUSION: The scheme recommends statements on specimen adequacy followed by the major classification category and then a subclassification and/or comments section. Each of the six main diagnostic categories is associated with an estimated risk of malignancy. Subsequent documents will propose ancillary testing recommendations, techniques for cytologic sampling, indications for cytologic study and postcytologic diagnosis management and follow-up recommendations. PMID- 26990837 TI - Sex and the PASI: patients affected by a mild form of psoriasis are more predisposed to have a more severe form of erectile dysfunction. AB - BACKGROUND: Psoriasis is a multi-systemic disease involving the skin and joints, but it is also characterized by endothelial dysfunction, which may cause sexual impotence and erectile dysfunction (ED), an embarrassing disease frequently neglected by dermatologists. OBJECTIVE: The principal objective was assessing the relationship between the severity of psoriasis and the severity of ED. We also investigated whether severity of psoriasis was related to International Index of Erectile Function-5 (IIEF-5) score, whether genital lesions worsened the IIEF-5 score, whether ED was related to factors such as diabetes, smoking and hypertension, and finally the overall the psychological factors felt by the patient. METHODS: We administered two questionnaires (one of which was the IIEF 5, a validated score to assess erectile dysfunction) to three groups of patients: 60 with mild psoriasis, 60 with severe psoriasis (assessed by Psoriasis Area Severity Index, PASI) and a control group including 60 patients without the disease. RESULTS: In the group of mild psoriasis, the patients who suffered from ED were the 56.67%, while in the group of severe psoriasis, ED affected the 46.68% of subjects. In the control group, ED was reported by the 23.33% of patients. The average IIEF-5 score was 18.81 for patients with mild psoriasis and 20.31 for patients with severe form. The difference in the average IIEF-5 scores between psoriatic (mild and severe cases) and control group was not statistically significant. Most patients with sexual dysfunction had also genital lesions; diabetes, smoking and hypertension were not related to lower IIEF-5 scores. The overall psychological profile of psoriatic patients was worse than that of the controls. CONCLUSION: We concluded that ED was related to psoriasis, in particular to mild forms. Moreover, since ED is a marker of cardiovascular events, also related to negative impact on the quality of life, physicians should always investigate the presence of ED in clinical practice. PMID- 26990838 TI - Novel application of nanozeolite for radioactive cesium removal from high-salt wastewater. AB - Finding a striking peculiarity of nanomaterials and evaluating its feasibility for practical use are interesting topics of research. We investigated the application of nanozeolite's outstanding reactivity for a rapid and effective method for radioactive cesium removal in the wastewater generated from nuclear power plant accident, as a new concept. Extremely fast removal of cesium, even without stirring, was achieved by the nanozeolite at efficiencies never observed with bulk materials. The nanozeolite reached an adsorption equilibrium state within 1 min. Cesium adsorption by nanozeolite was demonstrated at reaction rates of orders of magnitude higher than that of larger zeolite phases. This observation was strongly supported by the positive correlation between the rate constant ratio (k2,bulk/k2,nano) and the initial Cs concentrations with a correlation coefficient (R(2)) of 0.99. A potential drawback of a nanoadsorbent is the difficulty of particle settling and separation because of its high dispersivity in solution. However, our results also demonstrated that the nanozeolite could be easily precipitated from the high-salt solution with ferric flocculant. The flocculation index reached a steady state within 10 min. A series of our experimental results met the goal of rapid processing in the case of emergency by applying the well-suited nanozeolite adsorption and flocculation. PMID- 26990839 TI - Poly- and perfluoroalkyl substances in wastewater: Significance of unknown precursors, manufacturing shifts, and likely AFFF impacts. AB - In late 2014, wastewater effluent samples were collected from eight treatment plants that discharge to San Francisco (SF) Bay in order to assess poly- and perfluoroalkyl substances (PFASs) currently released from municipal and industrial sources. In addition to direct measurement of twenty specific PFAS analytes, the total concentration of perfluoroalkyl acid (PFAA) precursors was also indirectly measured by adapting a previously developed oxidation assay. Effluent from six municipal treatment plants contained similar amounts of total PFASs, with highest median concentrations of PFHxA (24 ng/L), followed by PFOA (23 ng/L), PFBA (19 ng/L), and PFOS (15 ng/L). Compared to SF Bay municipal wastewater samples collected in 2009, the short chain perfluorinated carboxylates PFBA and PFHxA rose significantly in concentration. Effluent samples from two treatment plants contained much higher levels of PFASs: over two samplings, wastewater from one municipal plant contained an average of 420 ng/L PFOS and wastewater from an airport industrial treatment plant contained 560 ng/L PFOS, 390 ng/L 6:2 FtS, 570 ng/L PFPeA, and 500 ng/L PFHxA. The elevated levels observed in effluent samples from these two plants are likely related to aqueous film forming foam (AFFF) sources impacting their influent; PFASs attributable to both current use and discontinued AFFF formulations were observed. Indirectly measured PFAA precursor compounds accounted for 33%-63% of the total molar concentration of PFASs across all effluent samples and the PFAA precursors indicated by the oxidation assay were predominately short-chained. PFAS levels in SF Bay effluent samples reflect the manufacturing shifts towards shorter chained PFASs while also demonstrating significant impacts from localized usage of AFFF. PMID- 26990840 TI - Efficacy of pomades containing different percentages of enilconazole in the treatment of bovine dermatophytosis. AB - BACKGROUND: Enilconazole is a broad-spectrum topical antimycotic agent used for the management of bovine dermatophytosis. HYPOTHESIS/OBJECTIVES: To investigate the efficacy of pomades containing different concentrations of enilconazole for the treatment of bovine dermatophytosis. METHODS: Dermatophytosis was confirmed in 120 cattle from farm in Gole region of Turkey. Animals were divided into six groups (n = 20 in each). Pomades containing 1%, 2%, 3%, 4% and 5% enilconazole were applied topically to individual lesions in groups I-V, respectively, once a day for 3 days. Group VI animals were used as a control group. Animals were monitored clinically once a week for a two month period. RESULTS: Cows treated with pomades containing 4% and 5% enilconazole recovered; adverse topical reactions occurred in 40% and 55% of animals, respectively. The success rate for cows treated with pomades containing 3% enilconazole was 95% and they recovered with no adverse reactions. Success rates for treatment were 25% and 50% for cows treated with pomades containing 1% and 2% enilconazole, respectively. No improvement was observed in the control group. CONCLUSIONS AND CLINICAL IMPORTANCE: Pomades containing 3% enilconazole are recommended for the treatment of bovine dermatophytosis. PMID- 26990841 TI - In-Depth Characterization and Spectral Library Building of Glycopeptides in the Tryptic Digest of a Monoclonal Antibody Using 1D and 2D LC-MS/MS. AB - This work presents a detailed analysis of glycopeptides produced in the tryptic digestion of an IgG1 reference material. Analysis was done by nanospray ESI LC MS/MS over a wide range of HCD collision energies with both conventional 1D separation for various digestion conditions and a 20 fraction 2D-LC study of a single digest. An extended version of NIST-developed software for analysis of "shotgun" proteomics served to identify the glycopeptides from their precursor masses and product ions for peptides with up to three missed cleavages. A peptide with a single missed cleavage, TKPREEQYNSTYR, was dominant and led to the determination of almost all glycans reported in this study. The 2D studies found a total of 247 glycopeptide ions and 60 glycans of different masses, including 30 glycans found in the 1D studies. This significantly larger number of glycans than found in any other glycoanalysis of therapeutic glycoproteins is due to both the improved separation of sialylated versus asialylated species in the first (high pH) dimension and the ability to inject large amounts of glycosylated peptides in the 2D studies. Systematic variations in retention with glycan size were also noted. Energy-dependent changes in HCD fragmentation confirmed the proposed glycan structures and led to a peak-annotated mass spectral library to aid the analysis of glycopeptides derived from IgG1 drugs. PMID- 26990842 TI - Keratinocyte Dystrophy as a Marker of Low-Dose Methotrexate-Induced Skin Toxicity: Comment on the Clinical Image by Monch et al. PMID- 26990843 TI - Effect of Cell Adhesion Molecules on the Neurite Outgrowth of Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons. AB - Intrastriatal transplantation of dopaminergic neurons has been shown to be a potentially very effective therapeutic approach for the treatment of Parkinson's disease (PD). With the detection of induced pluripotent stem cells (iPSCs), an unlimited source of autologous dopaminergic (DA) neurons became available. Although the iPSC-derived dopaminergic neurons exhibited most of the fundamental dopaminergic characteristics, detailed analysis and comparison with primary DA neurons have shown some aberrations in the expression of genes involved in neuronal development and neurite outgrowth. The limited outgrowth of the iPSC derived DA neurons may hamper their potential application in cell transplantation therapy for PD. In the present study, we examined whether the forced expression of L1 cell adhesion molecule (L1CAM) and polysialylated neuronal cell adhesion molecule (PSA-NCAM), via gene transduction, can promote the neurite formation and outgrowth of iPSC-derived DA neurons. In cultures on astrocyte layers, both adhesion factors significantly increased neurite formation of the adhesion factor overexpressing iPSC-derived DA neurons in comparison to control iPSC-derived DA neurons. The same tendency was observed when the DA neurons were plated on postnatal organotypic striatal slices; however, this effect did not reach statistical significance. Next, we examined the neurite outgrowth of the L1CAM- or PSA-NCAM-overexpressing iPSC-derived DA neurons after implantation in the striatum of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, the animal model for PD. Like the outgrowth on the organotypic striatal slices, no significant L1CAM- and PSA-NCAM-enforced neurite outgrowth of the implanted DA neurons was observed. Apparently, induced expression of L1CAM or PSA-NCAM in the iPSC-derived DA neurons cannot completely restore the neurite outgrowth potential that was reduced in these DA neurons as a consequence of epigenetic aberrations resulting from the iPSC reprogramming process. PMID- 26990844 TI - Assessment of Antishivering Medication Requirements During Therapeutic Normothermia: Effect of Cooling Methods. AB - Shivering during targeted temperature management (TTM) should be minimized because it can cause cerebral and metabolic stress. It has been proposed that surface cooling (SC) may result in more shivering than endovascular cooling (EC) methods. The purpose of this study was to compare antishivering medication requirements and degree of shivering in these groups during TTM to Normothermia (NT). This was a retrospective single-center cohort study of patients treated with protocolized TTM through SC and EC methods to achieve NT (37.0-37.5 degrees C). The number of interventions and daily dose of antishivering medications, per institutional protocol, were compared between the two groups. The intensity of shivering was assessed with the Bedside Shivering Assessment Scale. Patients in the EC group (n = 23) had more antishivering interventions per patient day than those in the SC group (n = 43) (3.28 vs. 2.67, p = 0.002). Acetaminophen (81% vs. 59%, p < 0.001), buspirone (75% vs. 53%, p < 0.001), and magnesium infusions (52% vs. 36%, p = 0.012) were used on more patient days in the EC group. Patients treated with SC required more patient days of propofol (35% vs. 19%, p = 0.006) and higher average dexmedetomidine dosing per patient-day (0.70 vs. 0.56 MUg/[kg.h], p = 0.03). Dosing of other medications was similar. There were no observed differences in degree or intensity of shivering. In our cohort, patients in EC group required more antishivering interventions, but less sedation, during TTM than patients in SC group. Optimizing nonsedating medications, such as acetaminophen, buspirone, and magnesium infusions, may decrease the requirement for sedatives to control shivering in both SC and EC. PMID- 26990845 TI - The effect of anthropogenic activity on BTEX, NO2, SO2, and CO concentrations in urban air of the spa city of Sopot and medium-industrialized city of Tczew located in North Poland. AB - The major goal of the present study is to compare the air quality of two urban locations situated in Northern Poland - the spa City of Sopot and the medium industrialized city of Tczew using chemometric methods. As a criterion for the assessment of atmospheric air quality, measurements of benzene, toluene, ethylbenzene and total xylenes were used (collected from atmospheric air using diffusion-type passive samplers) as well as measurements of inorganic compounds - CO, NO2 and SO2, which were subject to routine control and determined by means of automatic analysers. Studies related to determination of defined chemical compounds in the urban air in the monitored area were performed from January 2013 to December 2014. By interpreting the results obtained and using basic multivariate statistical tools (cluster analysis and principal components analysis), major sources of emissions of determined pollutants in the air in urbanized areas were defined. The study also shows the potential influence of the sea breeze on concentrations of chemical compounds in the atmospheric air in the spa city of Sopot. PMID- 26990846 TI - Effectiveness of interventions to reduce exposure to lead through consumer products and drinking water: A systematic review. AB - OBJECTIVES: The objective of this systematic review is to assess the effectiveness of regulatory, environmental and educational interventions for reducing blood lead levels (BLLs) and associated health outcomes in children, pregnant women and the general population. METHODS: Searches were run in MEDLINE, EMBASE and the Global Health Library up until August 2015. Studies were eligible for inclusion if they assessed the impact of regulatory, environmental or educational interventions, stand-alone or in combination, on BLLs among children, pregnant women or the general population through randomized controlled trials (RCT), controlled before-after (CBA), interrupted time series (ITS), uncontrolled before-after (UBA) or repeated cross-sectional studies. Studies assessing the impact of interventions to reduce exposure to lead in paint or household dust as well as studies concerned exclusively with environmental concentrations of lead were not included. As documented in a detailed protocol, screening, data extraction and quality appraisal were largely undertaken according to Cochrane standards. Harvest plots were used to graphically summarize evidence of effectiveness. RESULTS: The searches yielded 6466 unique records, of which five met our eligibility criteria; two additional eligible studies were identified by experts. We did not find any studies regarding the effectiveness of regulatory, educational or environmental interventions targeting exposure to lead in consumer products. Evidence regarding the effectiveness of interventions in reducing BLLs from exposures through drinking water is limited in both quantity and quality. Stand-alone targeted educational interventions showed no statistically significant reductions in children's BLL (two RCT) when compared to general educational interventions. Likewise, instructing women to reduce or eliminate lead-contaminated drinking water showed no effect on BLL (one RCT). Stand-alone environmental interventions appeared more promising in reducing BLL (three UBA). Combining educational and environmental interventions and targeting multiple settings may be effective in reducing BLL, as suggested by one uncontrolled before-after study. No studies examining the effectiveness of regulatory interventions were found. CONCLUSIONS: The limited quantity and quality of the evidence measuring BLL and associated health outcomes points to an urgent need for more robust research into the effectiveness of interventions to reduce lead exposure from consumer products and drinking water, especially for regulatory interventions. PMID- 26990847 TI - Exploring Medical Student Learning Needs in the Pediatric Emergency Department: "What Do You Want to Learn Right Now?". AB - BACKGROUND: When precepting medical students in the emergency department, faculty physicians often have only minutes per patient encounter to devote to direct teaching. Instructional strategies that promote independent student learning after each case may have merit. It is not known, however, to what degree patient triggered learning needs are amenable to independent study. OBJECTIVE: The aims of this study were to determine self- and faculty-reported learner needs at the time of patient encounters and to assess the degree to which these perceived needs may be satisfied by independent study. METHODS: We interviewed medical students and faculty in our pediatric emergency department. Immediately before or after they saw a patient, we asked "What do you want to learn right now?". For half of the student interviews, we separately asked the same questions of their preceptors. Interviews were taped and transcribed. Responses were coded by 3 investigators who did content analysis to identify dominant themes and the extent to which the learning need could be addressed independently. Investigators agreed that Accreditation Council for Graduate Medical Education competency domains could be used to classify the responses. RESULTS: We interviewed 82 students and 44 preceptors yielding 126 patient-triggered learning needs. Competency area(s) were medical knowledge (70), patient care (1), interpersonal skills (27), systems based practice (2), practice-based learning (3), and professionalism (4). Two raters independently assigned the same competency in 89%. Medical knowledge competency learning needs were almost all at least moderately amenable to independent learning (68/70, 98%), but the other competencies were not (22/57, 39%) according to the raters (interrater reliability, 0.7). Preceptor responses were congruent in competency type with students' responses in 29 (67%) of 43. Students listed interpersonal skills deficits far more often than did faculty (24% vs 5%, P < 0.05). CONCLUSIONS: Most student learning needs in the pediatric emergency department focus on medical knowledge. These deficits could be amenable to structured independent study at the point of care. PMID- 26990848 TI - Improving Pediatric Emergency Care by Implementing an Eligible Learner Endotracheal Intubation Policy. AB - OBJECTIVES: Although endotracheal intubations (ETIs) are high-risk, low-frequency events, there are no nationally accepted training pathways or measures to ensure ETI competence for emergency department (ED) providers. Our objective was to determine whether implementation of an eligible learner ETI policy (ELETIP) led to improved first ETI attempt success rates and decreased immediate airway related complications. METHODS: This was a retrospective cross-sectional before and-after study of outcomes after ELETIP implementation. The primary outcome was proportion of successful first ETI attempts; secondary outcomes were number of intubation attempts, time to intubation, need to call anesthesia for intubation, and airway-related complications. RESULTS: Three hundred ninety patients were included (median age, 1.3 y; range, 1 day-24.7 y): 219 (56%) and 171 (44%) in the pre- and post-ELETIP periods, respectively. First successful ETI attempts increased from 65.1% to 75.7% (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.07-2.62). Secondary outcomes included mean number of intubation attempts (1.6-1.4, P = 0.01), time to intubation (5.6-4.9 minutes, P = 0.07), anesthesia intubations in the ED (5.9%-2.9%; OR, 0.48; 95% CI, 0.17-1.37), and intubation related complications (32%-25.7%; OR, 0.74; 95% CI, 0.47-1.15). CONCLUSIONS: An ELETIP is effective in improving ED care by increasing first ETI attempt success rates while decreasing overall intubation attempts. Physicians and physician learners with anesthesia training for critical airway management training have high ETI attempt success rates. Airway management training is essential to physician education and airway management skills for improving outcomes. PMID- 26990849 TI - Development and Evaluation of a Learning Intervention Targeting First-Year Resident Defibrillation Skills. AB - OBJECTIVES: The aim of the study was to evaluate an educational intervention targeting the acquisition and retention of critical core skills of defibrillation in first-year pediatric residents using simulation-based training and deliberate practice. METHODS: From January 2011 to April 2012, a total of 23 first-year pediatric residents participated in a pretest-posttest study. An initial survey evaluated previous experience, training, and comfort. The scoring tool was designed and validated using a standard setting procedure and 60% was determined to be the minimum passing score. The 1-hour educational intervention included a brief video describing the defibrillator, 10 to 15 minutes of hands-on time with the defibrillator, and 30 minutes of simulation-based scenarios using deliberate practice with real-time feedback. RESULTS: The number of subjects who achieved competency in defibrillation skills increased from 8 to 16 of 23 (35% vs 70%, P < 0.05), pretest versus posttest, with the posttest occurring 4 months after the intervention. There was a significant improvement in checklist score (53% vs 68%, P < 0.05) and time to defibrillation (282-189 s, P < 0.05). For those who initiated chest compressions, there was a nonsignificant improvement in time to compressions (50 vs 33 s, P = 0.08). Previous Pediatric Advanced Life Support training was not associated with performance on pretest or posttest. CONCLUSIONS: This brief educational intervention was shown to be effective 4 months after instruction in achieving and retaining competency of defibrillation skills by first-year pediatric residents. In the process, we uncovered educational gaps in cardiopulmonary resuscitation and other resuscitation skills that need to be addressed in future educational interventions and training. PMID- 26990850 TI - Meta-analysis of the concordance of histological grade of breast cancer between core needle biopsy and surgical excision specimen. AB - BACKGROUND: With the increasing use of neoadjuvant chemotherapy and minimally invasive ablative therapy in breast cancer, pretreatment assessment of tumour grade on core needle biopsy (CNB) is increasingly needed. However, grading on CNB is possibly less accurate than grading based on the surgical excision specimen. A systematic review and meta-analysis of the literature was conducted to derive a reliable estimate of the agreement in tumour grading between CNB and subsequent surgical excision. METHODS: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria, Embase, PubMed and the Cochrane Library were searched. Pooled proportions of agreement in grading between CNB and the excision specimen, Cohen's kappa and percentages of overestimation and underestimation were calculated. Random-effects models were applied because of substantial heterogeneity, assessed by I2 test. Determinants of the level of agreement in grading were explored with meta-regression. RESULTS: Thirty-four articles were included in the systematic review (6029 patients) and 33 in the meta-analysis (4980 patients). Pooled agreement and kappa were 71.1 (95 per cent c.i. 68.8 to 73.3) per cent and 0.54 (0.50 to 0.58) respectively. Underestimation and overestimation occurred in 19.1 (17.1 to 21.3) and 9.3 (7.7 to 11.4) per cent respectively. Meta-regression showed associations between agreement of histological type (positive association) and proportion of patients with oestrogen receptor-positive disease (negative association) and grade agreement. CONCLUSION: Grading on CNB corresponds moderately with grading based on excision specimens, with underestimation in about one in five patients. Incorrect CNB tumour grading has limited clinical implications, as multiple factors influence decision-making for adjuvant systemic therapy. PMID- 26990851 TI - See, smell, eat in moderation--Or how an assumed homeostatic mechanism can be influenced by anticipatory perception. PMID- 26990852 TI - Renal endothelial protein C receptor expression and shedding during diabetic nephropathy. AB - Essentials Endothelial protein C receptor (EPCR) promotes diabetic nephropathy (DN) outcome improvement. Renal expression and shedding of EPCR were measured in diabetic patients with or without DN. Inhibition of metalloproteinase-driven EPCR shedding restored glomerular endothelium phenotype. EPCR shedding through metalloproteinase ADAM17 contributes to the worsening of DN. SUMMARY: Background Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease. The endothelial protein C receptor (EPCR) and its ligand (activated protein C) have been shown to ameliorate the phenotype of DN in mice. EPCR activity can be regulated by proteolytic cleavage involving ADAMs, yielding a soluble form of EPCR (sEPCR). Objective To characterize the renal expression and shedding of EPCR during DN. Methods EPCR levels were measured in plasma, urine and biopsy samples of diabetic patients with (n = 73) or without (n = 63) DN. ADAM-induced cleavage of EPCR was investigated in vitro with a human glomerular endothelium cell line. Results DN patients showed higher plasma and urinary levels of sEPCR than diabetic controls (112.2 versus 135.2 ng mL(-1) and 94.35 versus 140.6 ng mL(-1) , respectively). Accordingly, glomerular endothelial EPCR expression was markedly reduced in patients with DN, and this was associated with increased glomerular expression of ADAM-17 and ADAM-10. In vitro, EPCR shedding was induced by incubation of glomerular endothelium in high-glucose medium, and this shedding was suppressed by ADAM-17 inhibition or silencing, which led to improved vascular endothelial cadherin (VE-cadherin) expression and reduced mRNA expression of transforming growth factor (TGF)-beta. In addition, EPCR silencing led to minor effects on VE-cadherin but to a significant increase in TGF-beta mRNA expression. Conclusion Inhibition of ADAM-driven glomerular EPCR shedding restored the endothelial phenotype of glomerular endothelium, whereas EPCR silencing led to enhanced expression of TGF-beta, a marker of endothelial mesenchymal transition. These findings demonstrate that EPCR shedding driven by ADAMs contributes to the worsening of DN. PMID- 26990853 TI - Emergent verbal behavior in preschool children learning a second language. AB - We evaluated the emergence of untaught second-language skills following directly taught listener and intraverbal responses. Three preschool children were taught first-language (English) listener responses (e.g., "Point to the horse") and second-language (Welsh) intraverbal responses (e.g., "What is horse in Welsh?" [ceffyl]). After intervention, increases in untaught second-language tacts (e.g., "What is this in Welsh?" [ceffyl]) and listener responses (e.g., "Point to the ceffyl") were observed for all 3 participants. PMID- 26990854 TI - Primary Glial and Neuronal Tumors of the Ovary or Peritoneum: A Clinicopathologic Study of 11 Cases. AB - Primary glial and neuronal tumors of the ovary or peritoneum are rare neuroectodermal-type tumors similar to their counterparts in the central nervous system. We retrospectively reviewed 11 cases. These cases included 4 ependymomas, 6 astrocytic tumors, and 1 neurocytoma. Patients' age ranged from 9 to 50 years (mean, 26 y; median, 24 y). All ependymal tumors with detailed clinical history (n=3) were not associated with any other ovarian neoplasm. In contrast, all astrocytic tumors were associated with immature teratoma (n=4), mature cystic teratoma (n=1), or mixed germ cell tumor (n=1). The neurocytoma arose in association with mature teratomatous components in a patient with a history of treated mixed germ cell tumor. Immunohistochemical staining showed that 7 of 7 ependymal and astrocytic tumors (100%) were positive for glial fibrillary acidic protein, and 2 of 2 ependymomas (100%) were positive for both estrogen and progesterone receptors. The neurocytoma was positive for synaptophysin and negative for S100 protein, glial fibrillary acidic protein, and SALL4. No IDH1 R132H mutation was detected in 2 of 2 (0%) astrocytomas by immunohistochemistry. Next-generation sequencing was performed on additional 2 ependymomas and 2 astrocytomas but detected no mutations in a panel of 50 genes that included IDH1, IDH2, TP53, PIK3CA, EGFR, BRAF, and PTEN. Follow-up information was available for 8 patients, with the follow-up period ranging from 4 to 59 months (mean, 15 mo; median, 8.5 mo), of which 3 had no evidence of disease and 5 were alive with disease. In conclusion, primary glial and neuronal tumors of the ovary can arise independently or in association with other ovarian germ cell tumor components. Pathologists should be aware of these rare tumors and differentiate them from other ovarian neoplasms. Even though an IDH1 or IDH2 mutation is found in the majority of WHO grade II and III astrocytomas, and in secondary glioblastomas arising from them, such mutations were not identified in our series, suggesting that these tumors are molecularly different from their central nervous system counterparts despite their morphologic and immunophenotypic similarities. PMID- 26990856 TI - Meaning in Life Buffers the Association Between Risk Factors for Suicide and Hopelessness in Participants With Mental Disorders. AB - OBJECTIVE: Hopelessness is a proximal risk factor of suicide. Meaning in life has been found to be a protective factor against suicidal ideation; however, the majority of studies that have explored the role of meaning in life in the context of suicidality have been conducted in nonclinical populations. The aim of this study was to investigate whether meaning in life can moderate and buffer the association between suicide risk factors and hopelessness in a clinical sample with a heightened risk of suicide. METHOD: A total of 224 participants diagnosed with mental disorders completed self-report measures of suicide risk factors, hopelessness, and meaning in life. RESULTS: The main result from this study was that meaning in life moderated the association between suicide risk factors and hopelessness. CONCLUSION: Meaning in life is an important variable in the prevention and treatment of people at risk of suicide. PMID- 26990857 TI - Metal Stable Isotope Tagging: Renaissance of Radioimmunoassay for Multiplex and Absolute Quantification of Biomolecules. AB - The unambiguous quantification of biomolecules is of great significance in fundamental biological research as well as practical clinical diagnosis. Due to the lack of a detectable moiety, the direct and highly sensitive quantification of biomolecules is often a "mission impossible". Consequently, tagging strategies to introduce detectable moieties for labeling target biomolecules were invented, which had a long and significant impact on studies of biomolecules in the past decades. For instance, immunoassays have been developed with radioisotope tagging by Yalow and Berson in the late 1950s. The later languishment of this technology can be almost exclusively ascribed to the use of radioactive isotopes, which led to the development of nonradioactive tagging strategy-based assays such as enzyme linked immunosorbent assay, fluorescent immunoassay, and chemiluminescent and electrochemiluminescent immunoassay. Despite great success, these strategies suffered from drawbacks such as limited spectral window capacity for multiplex detection and inability to provide absolute quantification of biomolecules. After recalling the sequences of tagging strategies, an apparent question is why not use stable isotopes from the start? A reasonable explanation is the lack of reliable means for accurate and precise quantification of stable isotopes at that time. The situation has changed greatly at present, since several atomic mass spectrometric measures for metal stable isotopes have been developed. Among the newly developed techniques, inductively coupled plasma mass spectrometry is an ideal technique to determine metal stable isotope-tagged biomolecules, for its high sensitivity, wide dynamic linear range, and more importantly multiplex and absolute quantification ability. Since the first published report by our group, metal stable isotope tagging has become a revolutionary technique and gained great success in biomolecule quantification. An exciting research highlight in this area is the development and application of the mass cytometer, which fully exploited the multiplexing potential of metal stable isotope tagging. It realized the simultaneous detection of dozens of parameters in single cells, accurate immunophenotyping in cell populations, through modeling of intracellular signaling network and undoubted discrimination of function and connection of cell subsets. Metal stable isotope tagging has great potential applications in hematopoiesis, immunology, stem cells, cancer, and drug screening related research and opened a post-fluorescence era of cytometry. Herein, we review the development of biomolecule quantification using metal stable isotope tagging. Particularly, the power of multiplex and absolute quantification is demonstrated. We address the advantages, applicable situations, and limitations of metal stable isotope tagging strategies and propose suggestions for future developments. The transfer of enzymatic or fluorescent tagging to metal stable isotope tagging may occur in many aspects of biological and clinical practices in the near future, just as the revolution from radioactive isotope tagging to fluorescent tagging happened in the past. PMID- 26990858 TI - Thermoresponsive Polymer and Fluorescent Dye Hybrids for Tunable Multicolor Emission. AB - Fully reversible emission color change is achieved by blending a thermoresponsive polymer with dye hybrids. The emission color can be tuned by changing the mixing ratio of each polymer-dye hybrid. PMID- 26990855 TI - Granulocyte colony-stimulating factor impairs CD8(+) T cell functionality by interfering with central activation elements. AB - Besides mobilizing stem cells into the periphery, granulocyte colony-stimulating factor (G-CSF) has been shown to influence various types of innate and adaptive immune cells. For example, it impairs the effector function of cytotoxic T lymphocytes (CTLs). It is assumed that this effect is mediated indirectly by monocytes, regulatory T cells and immunomodulatory cytokines influenced by G-CSF. In this study, isolated G-CSF-treated CD8(+) T cells were stimulated antigen dependently with peptide-major histocompatibility complex (pMHC)-coupled artificial antigen-presenting cells (aAPCs) or stimulated antigen-independently with anti-CD3/CD28 stimulator beads. By measuring the changes in interferon (IFN) gamma and granzyme B expression at the mRNA and protein level, we showed for the first time that G-CSF has a direct effect on CD8(+) CTLs, which was confirmed based on the reduced production of IFN-gamma and granzyme B by the cytotoxic T cell line TALL-104 after G-CSF treatment. By investigating further elements affected by G-CSF in CTLs from stem cell donors and untreated controls, we found a decreased phosphorylation of extracellular-regulated kinase (ERK)1/2, lymphocyte-specific protein tyrosine kinase (Lck) and CD3zeta after G-CSF treatment. Additionally, miRNA-155 and activation marker expression levels were reduced. In summary, our results show that G-CSF directly influences the effector function of cytotoxic CD8(+) T cells and affects various elements of T cell activation. PMID- 26990859 TI - Synthesis and anticancer activity of carbosilane metallodendrimers based on arene ruthenium(ii) complexes. AB - A series of new organometallic carbosilane dendrimers (first and second generation) and the corresponding non-dendritic mononuclear based on ruthenium arene fragments are described. The metallodendrimers were prepared by reactions of the precursor [Ru(eta(6)-p-cymene)Cl2]2 with carbosilane dendrimers functionalized with N-donor monodentate ligands such as NH2- and pyridine, or with N,O-, N,N-chelating imine ligands. While the dendrimer precursors are insoluble in DMSO or water, novel metallodendrimers are soluble in DMSO and some of them are even highly soluble in water. The molecular structure of the "Ru-NH2" mononuclear compound (zero generation) was determined by single-crystal X-ray crystallography. The cytotoxicity activity of these dendritic structures was evaluated in several human cancer cell lines and compared with that of the corresponding mononuclear ruthenium complexes. Most compounds display significant cytotoxic activities in the low micromolar range with the first generation ruthenium dendrimers being the most active compounds. The cell death type for selected compounds has been studied as well as their reactivity towards relevant biomolecules such as DNA, Human Serum Albumin (HSA) and Cathepsin-B. All the data point to a mode of action different from that of cisplatin for most complexes. First generation ruthenium dendrimers inhibit Cathepsin-B, which may suggest potential antimetastatic properties of these compounds. PMID- 26990860 TI - Generation of Directly Converted Human Osteoblasts That Are Free of Exogenous Gene and Xenogenic Protein. AB - Generation of osteoblasts from human somatic cells may be applicable in an effective transplantation therapy against bone diseases. Recently we established a procedure to directly convert human fibroblasts into osteoblasts by transducing some transcription factor genes via retroviral vectors. However, retroviral vector-mediated transduction may potentially cause tumor formation from the infected cells, thus a non-viral gene transfection method may be more preferable for preparation of osteoblasts to be used for transplantation therapy. Here, we constructed a plasmid vector encoding Oct4, Osterix, and L-Myc that were an appropriate combination of transcription factors for this purpose. Osteoblast like phenotypes including high alkaline phosphatase (ALP) activity, bone matrix production and osteoblast-specific gene expression were induced in normal human fibroblasts that were transfected with the plasmid followed by culturing in osteogenic medium. The plasmid-driven directly converted osteoblasts (p-dOBs) were obtained even in the absence of a xenogenic protein. The plasmid vector sequence had fallen out of the p-dOBs. The cells formed deposition of calcified bodies in situ after transplantation into mice. These results strongly suggest that p-dOBs can be put into practical use for a novel cell-based therapy against bone diseases. J. Cell. Biochem. 117: 2538-2545, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990861 TI - PRKRA Mutation Causing Early-Onset Generalized Dystonia-Parkinsonism (DYT16) in an Italian Family. PMID- 26990863 TI - A retrospective analysis of the Alzheimer's disease vaccine progress - The critical need for new development strategies. AB - The promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks. It has been problematic to use conjugated peptides with Th1/Th2 adjuvants to induce immune responses against conformational epitopes formed by Abeta oligomers, which is critical to induce protective antibodies. Hence, vaccination should mimic natural immunity by using whole or if possible conjugated antigens, but biasing the response to Th2 with anti-inflammatory adjuvants. Also, selection of the carrier and cross-linking agents is important to prevent suppression of the immune response against the antigen. That certain compounds having phosphorylcholine or fucose induce a sole Th2 immunity would allow antigens with T-cell epitopes without inflammatory autoimmune reactions to be used. Another immunization method is DNA vaccines combined with antigenic ones, which favors the clonal selection and expansion of high affinity antibodies needed for immune protection, but this also requires Th2 immunity. Since AD transgenic mouse models have limited value for immunogen selection as shown by the clinical studies, screening may require the use of validated antibodies and biophysical methods to identify the antigens that would be most likely recognized by the human immune system and thus capable to stimulate a protective antibody response. To induce an anti-Alzheimer's disease protective immunity and prevent possible damage triggered by antigens having B-cell epitopes-only, whole antigens might be used; while inducing Th2 immunity with sole anti-inflammatory fucose based adjuvants. This approach would avert a damaging systemic inflammatory immunity and the suppression of immunoresponse against the antigen because of carrier and cross-linkers; immune requirements that extend to DNA vaccines. PMID- 26990862 TI - High-Resolution Denitrification Kinetics in Pasture Soils Link N2O Emissions to pH, and Denitrification to C Mineralization. AB - Denitrification in pasture soils is mediated by microbial and physicochemical processes leading to nitrogen loss through the emission of N2O and N2. It is known that N2O reduction to N2 is impaired by low soil pH yet controversy remains as inconsistent use of soil pH measurement methods by researchers, and differences in analytical methods between studies, undermine direct comparison of results. In addition, the link between denitrification and N2O emissions in response to carbon (C) mineralization and pH in different pasture soils is still not well described. We hypothesized that potential denitrification rate and aerobic respiration rate would be positively associated with soils. This relationship was predicted to be more robust when a high resolution analysis is performed as opposed to a single time point comparison. We tested this by characterizing 13 different temperate pasture soils from northern and southern hemispheres sites (Ireland and New Zealand) using a fully automated-high resolution GC detection system that allowed us to detect a wide range of gas emissions simultaneously. We also compared the impact of using different extractants for determining pH on our conclusions. In all pH measurements, soil pH was strongly and negatively associated with both N2O production index (IN2O) and N2O/(N2O+N2) product ratio. Furthermore, emission kinetics across all soils revealed that the denitrification rates under anoxic conditions (NO+N2O+N2 MUmol N/h/vial) were significantly associated with C mineralization (CO2 MUmol/h/vial) measured both under oxic (r2 = 0.62, p = 0.0015) and anoxic (r2 = 0.89, p<0.0001) conditions. PMID- 26990864 TI - Social Learning in Vespula Germanica Wasps: Do They Use Collective Foraging Strategies? AB - Vespula germanica is a social wasp that has become established outside its native range in many regions of the world, becoming a major pest in the invaded areas. In the present work we analyze social communication processes used by V. germanica when exploiting un-depleted food sources. For this purpose, we investigated the arrival pattern of wasps at a protein bait and evaluated whether a forager recruited conspecifics in three different situations: foragers were able to return to the nest (full communication), foragers were removed on arrival (communication impeded), or only one forager was allowed to return to the nest (local enhancement restricted). Results demonstrated the existence of recruitment in V. germanica, given that very different patterns of wasp arrivals and a higher frequency of wasp visits to the resource were observed when communication flow between experienced and naive foragers was allowed. Our findings showed that recruitment takes place at a distance from the food source, in addition to local enhancement. When both local enhancement and distant recruitment were occurring simultaneously, the pattern of wasp arrival was exponential. When recruitment occurred only distant from the feeder, the arrival pattern was linear, but the number of wasps arriving was twice as many as when neither communication nor local enhancement was allowed. Moreover, when return to the nest was impeded, wasp arrival at the bait was regular and constant, indicating that naive wasps forage individually and are not spatially aggregated. In conclusion, this is the first study to demonstrate recruitment in V. germanica at a distance from the food source by modelling wasps' arrival to a protein-based resource. In addition, the existence of correlations when communication was allowed and reflected in tandem arrivals indicates that we were not in the presence of random processes. PMID- 26990865 TI - Net Carbon Emissions from Deforestation in Bolivia during 1990-2000 and 2000 2010: Results from a Carbon Bookkeeping Model. AB - Accurate estimates of global carbon emissions are critical for understanding global warming. This paper estimates net carbon emissions from land use change in Bolivia during the periods 1990-2000 and 2000-2010 using a model that takes into account deforestation, forest degradation, forest regrowth, gradual carbon decomposition and accumulation, as well as heterogeneity in both above ground and below ground carbon contents at the 10 by 10 km grid level. The approach permits detailed maps of net emissions by region and type of land cover. We estimate that net CO2 emissions from land use change in Bolivia increased from about 65 million tons per year during 1990-2000 to about 93 million tons per year during 2000 2010, while CO2 emissions per capita and per unit of GDP have remained fairly stable over the sample period. If we allow for estimated biomass increases in mature forests, net CO2 emissions drop to close to zero. Finally, we find these results are robust to alternative methods of calculating emissions. PMID- 26990866 TI - A stratified analysis of the perioperative outcome of 17623 patients undergoing major head and neck cancer surgery in England over 10 years: Towards an Informatics-based Outcomes Surveillance Framework. AB - OBJECTIVES: To perform a national analysis of the perioperative outcome of major head and neck cancer surgery to develop a stratification strategy and outcomes assessment framework using hospital administrative data. DESIGN: A Hospital Episode Statistics N = near-all analysis. SETTINGS: The English National Health Service. MAIN OUTCOME MEASURES: Local audit data were used to assess and triangulate the quality of the administrative dataset. Within the national dataset, cancer sites, morbidities, social deprivation, treatment, complications, and in-hospital mortality were recorded. RESULTS: Within local audit datasets, the accuracy of assigning newly-derived Cancer Site Strata and Resection Strata were 92.3% and 94.2%, respectively. Accuracy of morbidities assignment was 97%. Within the national dataset, we identified 17 623 major head and neck cancer resections between 2002 and 2012. There were 12 413 males and mean age at surgery was 63 +/- 12 years. The commonest cancer site strata were oral cavity (42%) and larynx-hypopharynx (32%). The commonest resection site was the larynx (n = 4217), and 13 211 and 11 841 patients had neck dissection and flap-based reconstruction, respectively. There were prognostically significant baseline differences between patients with oromandibular and pharyngolaryngeal malignancy. Patients with pharyngolaryngeal malignancies had a greater burden of morbidities, lower socio economic status, fewer primary resections, and a sixfold increased risk of undergoing their major resection during an emergency hospital admission. Mean length of stay was 25 days and each complication linearly increased it by 9.6 days. There were 609 (3.5%) in-hospital deaths and a basket of seven medical and three surgical complications significantly increased the risk of in-hospital death. At least one potentially lethal complication occurred in 26% of patients. The risk of in-hospital death in a patient with no potentially lethal complication was 1.1% and this increased to 6% with one potentially lethal complication, and to 15.1% if two potentially lethal complications occurred in one patient. Complex oral-pharyngeal resections and pharyngolaryngectomies had the highest risks of complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows variation across different resection strata. We propose an Informatics-based Framework for Outcomes Surveillance (IFOS) in Head and Neck Surgery for perpetual quality assurance, using the local hospital coding data or its collated destination, the national administrative dataset. PMID- 26990867 TI - The Effect of Vaginal Oestriol Cream on Subjective and Objective Symptoms of Stress Urinary Incontinence and Vaginal Atrophy: An International Multi-Centre Pilot Study. AB - AIM: Subjectively and objectively assess stress urinary incontinence (SUI) symptoms before and after topical oestrogen therapy. METHODS: A prospective study was performed in 3 centres in South-Africa, Australia and the Netherlands. Postmenopausal women with SUI were treated with topical oestriol cream for 6 weeks. The primary subjective outcome was the Patient's Global Impression of Improvement (PGI-I) scale. The primary objective outcome was vaginal pH. Secondary subjective outcomes were: the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form, the Incontinence Impact Questionnaire, the Urogenital Distress Inventory (UDI-6) and the most bothersome symptom approach. Secondary objective outcome was the erect cough pad test. Compliance was scored. RESULTS: A total of 68 women were enrolled. Half of the participants reported improvement on the PGI-I scale after treatment. Vaginal pH was significantly lower after treatment (median 5.3 (interquartile range (IQR) 4.5-6.0) vs. 5.0 (4.4-5.4), p = 0.002). Improvement on the UDI stress domain was observed (p = 0.01). No statistically significant differences were found in the other subjective outcomes. Baseline and repeat cough pad tests demonstrated a wide variation with no significant difference. Compliance was high (median 100 (IQR 83-100%)). CONCLUSION: Topical oestriol cream during 6 weeks improved quality of life and vaginal pH but no other objective measures of incontinence. PMID- 26990868 TI - Candidate Soluble Immune Mediators in Young Women with High-Risk Human Papillomavirus Infection: High Expression of Chemokines Promoting Angiogenesis and Cell Proliferation. AB - BACKGROUND: The causal interpretation of cervical immune response to Human Papillomavirus (HPV) infection is complex and poorly characterized mainly due to the delicate balance that exists between viral infection, increase of inflammatory cytokines and host risk factors. This study aims to explore the significance of cervical immune mediators associated to cell survival, angiogenesis and interaction with immune response, in predicting the risk to develop HPV-related intraepithelial lesions. METHODS: A panel of 48 cytokines and growth factors were explored in a selected cohort of 168 immunocompetent women including 88 diagnosed with low (LSIL) or high (HSIL) squamous intraepithelial lesions of the cervix and 80 with normal cervical cytology (NIL). HPV genotyping was performed by Linear Array HPV test and the soluble concentration of 48 immune molecules was analyzed using the Bio-Plex platform. RESULTS: The prevalence of single HR-HPV infection was 30% in NIL and 100% in LSIL and HSIL women. The expression of 13 cytokines, including interleukins IL-6, IL-3, IL-12p40, IL 12p70, IL-16, IL-18, LIF, of chemokines CCL7 (MCP-3), CXCL9 (MIG), CXCL12 (SDF 1alpha) and of the tropic factors VEGF, G-CSF, M-CSF were significantly associated with the presence of infection, with levels being higher in women with precancerous lesions compared to NIL HPV negative women. Only the growth factor GM-CSF was positively associated with the cytological abnormalities. CONCLUSIONS: The ability of HR-HPV to escape from innate immune recognition and to orchestrate the production of specific inflammatory and growth factors, involved in early inflammatory response and in the cell-proliferating phase of intraepithelial damage, was documented in women before the development of cervical lesions. PMID- 26990869 TI - Further Evidence of Increasing Diversity of Plasmodium vivax in the Republic of Korea in Recent Years. AB - BACKGROUND: Vivax malaria was successfully eliminated from the Republic of Korea (ROK) in the late 1970s but re-emerged in 1993. Two decades later as the ROK enters the final stages of malaria elimination, dedicated surveillance of the local P. vivax population is critical. We apply a population genetic approach to gauge P. vivax transmission dynamics in the ROK between 2010 and 2012. METHODOLOGY/PRINCIPAL FINDINGS: P. vivax positive blood samples from 98 autochthonous cases were collected from patients attending health centers in the ROK in 2010 (n = 27), 2011 (n = 48) and 2012 (n = 23). Parasite genotyping was undertaken at 9 tandem repeat markers. Although not reaching significance, a trend of increasing population diversity was observed from 2010 (HE = 0.50 +/- 0.11) to 2011 (HE = 0.56 +/- 0.08) and 2012 (HE = 0.60 +/- 0.06). Conversely, linkage disequilibrium declined during the same period: IAS = 0.15 in 2010 (P = 0.010), 0.09 in 2011 (P = 0.010) and 0.05 in 2012 (P = 0.010). In combination with data from other ROK studies undertaken between 1994 and 2007, our results are consistent with increasing parasite divergence since re-emergence. Polyclonal infections were rare (3% infections) suggesting that local out-crossing alone was unlikely to explain the increased divergence. Cases introduced from an external reservoir may therefore have contributed to the increased diversity. Aside from one isolate, all infections carried a short MS20 allele (142 or 149 bp), not observed in other studies in tropical endemic countries despite high diversity, inferring that these regions are unlikely reservoirs. CONCLUSIONS: Whilst a number of factors may explain the observed population genetic trends, the available evidence suggests that an external geographic reservoir with moderate diversity sustains the majority of P. vivax infection in the ROK, with important implications for malaria elimination. PMID- 26990870 TI - Methylation of Epstein-Barr virus Rta promoter in EBV primary infection, reactivation and lymphoproliferation. AB - During Epstein-Barr virus (EBV) latency, the EBV genome is largely silenced by methylation. This silencing is overturned during the switch to the lytic cycle. A key event is the production of the viral protein Zta which binds to three Zta response elements (ZRE) from the Rta promoter (Rp), two of which (ZRE2 and ZRE3) include three CpG motifs methylated in the latent genome. The bisulphite pyrosequencing reaction was used to quantify the methylation of ZRE2, ZRE3a, and ZRE3b in EBV-positive cell lines and in ex vivo samples of EBV-related diseases, in order to assess whether the level of methylation in these ZREs could provide additional information to viral DNA load and serology in the characterization of EBV-associated diseases. In PBMC from two patients with infectious mononucleosis, over time Rp became increasingly methylated whereas EBV load decreased. In tonsil from patients with chronic tonsillitis, the methylation was less than in EBV associated tumors, regardless of the viral load. This was even more striking when only the ZRE3a and ZRE3b were considered since some samples presented unbalanced profiles on ZRE2. EBV reactivation in cell culture showed that the reduction in the overall level of methylation was closely related to the production of unmethylated virions. Thus, an assessment of the level of methylation may help to better characterize EBV replication in PBMC and in biopsies with high EBV load, during infectious mononucleosis and EBV-associated cancers. J. Med. Virol. 88:1814-1820, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990871 TI - Delta method and bootstrap in linear mixed models to estimate a proportion when no event is observed: application to intralesional resection in bone tumor surgery. AB - Resecting bone tumors requires good cutting accuracy to reduce the occurrence of local recurrence. This issue is considerably reduced with a navigated technology. The estimation of extreme proportions is challenging especially with small or moderate sample sizes. When no success is observed, the commonly used binomial proportion confidence interval is not suitable while the rule of three provides a simple solution. Unfortunately, these approaches are unable to differentiate between different unobserved events. Different delta methods and bootstrap procedures are compared in univariate and linear mixed models with simulations and real data by assuming the normality. The delta method on the z-score and parametric bootstrap provide similar results but the delta method requires the estimation of the covariance matrix of the estimates. In mixed models, the observed Fisher information matrix with unbounded variance components should be preferred. The parametric bootstrap, easier to apply, outperforms the delta method for larger sample sizes but it may be time costly. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990872 TI - Validation of a sample pretreatment protocol to convert a drug-sensitive into a drug-tolerant anti-infliximab antibody immunoassay. AB - A meta-analysis revealed that up to 51% of patients treated with infliximab develop anti-drug Abs (ADA) which are associated with loss of response. Detection of ADA is strongly influenced by assay technique since drug-sensitive ADA assays are not able to detect ADA in the presence of drug and therefore underestimate ADA development. In addition, the lack of a calibrator antibody that can be used in a drug-sensitive and drug-tolerant assay hampers an adequate comparison among different assays. Here we present a sample pretreatment protocol to convert the bridging assay, originally developed as a drug-sensitive assay, into a drug tolerant assay, allowing use of the same assay and calibrator antibody MA IFX10F9. Using the sample pretreatment protocol, the bridging assay detects antibodies towards infliximab in samples containing up to 5-fold infliximab over anti-infliximab. Analysis of consecutive serum samples from infliximab treated patients revealed that the drug-tolerant assay detects ADA development up to 40 weeks earlier compared to the drug-sensitive assay. In conclusion, the sample pretreatment protocol can be implemented in various assay formats and allows determination of ADA in the presence of drug, providing the possibility for early treatment optimization. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990873 TI - Declines in both redundant and trace species characterize the latitudinal diversity gradient in tintinnid ciliates. AB - The latitudinal diversity gradient is a well-known biogeographic pattern. However, rarely considered is how a cline in species richness may be reflected in the characteristics of species assemblages. Fewer species may equal fewer distinct ecological types, or declines in redundancy (species functionally similar to one another) or fewer trace species, those occurring in very low concentrations. We focused on tintinnid ciliates of the microzooplankton in which the ciliate cell is housed inside a species-specific lorica or shell. The size of lorica oral aperture, the lorica oral diameter (LOD), is correlated with a preferred prey size and maximum growth rate. Consequently, species of a distinct LOD are distinct in key ecologic characteristics, whereas those of a similar LOD are functionally similar or redundant species. We sampled from East Sea/Sea of Japan to the High Arctic Sea. We determined abundance distributions of biological species and also ecological types by grouping species in LOD size-classes, sets of ecologically similar species. In lower latitudes there are more trace species, more size-classes and the dominant species are accompanied by many apparently ecologically similar species, presumably able to replace the dominant species, at least with regard to the size of prey exploited. Such redundancy appears to decline markedly with latitude in assemblages of tintinnid ciliates. Furthermore, the relatively small species pools of the northern high latitude assemblages suggest a low capacity to adapt to changing conditions. PMID- 26990875 TI - Downregulation of erythroid differentiation regulator 1 (Erdr1) plays a critical role in psoriasis pathogenesis. PMID- 26990874 TI - Evaluation of cell and matrix mechanics using fluorescence excitation spectroscopy: Feasibility study in collagen gels containing fibroblasts. AB - BACKGROUND AND OBJECTIVE: Collagen gels containing cells are commonly used in tissue engineering, wound healing, and cancer research to investigate the interplay between cells and the extracellular matrix (ECM), as changes in the density and stiffness of the microenvironment are known to play a role in many diseases or pathological conditions. In these gels, the stiffness is regularly determined using destructive methods, such as indentation and tensile tests. Certain molecules native to cells and the ECM display fluorescence upon irradiation with ultraviolet light. The objective of the present study was to investigate the feasibility of using the endogenous, or innate, fluorescence of collagen gels containing fibroblasts as an optical marker to evaluate changes in the mechanical properties of the ECM. MATERIALS AND METHODS: Human foreskin fibroblasts cells at concentrations of 50,000 and 100,000 cells/ml were cultured in three-dimensional gels of type I collagen for 16 days. Fibroblast cells remodeled the ECM, contracting and increasing the stiffness of the gel. During this remodeling process, changes in mechanical properties and fluorescence were measured with an indentation test and a spectrofluorometer, respectively. Force and displacement measurements from the indentation test were used to calculate the elastic modulus of the gel. Maps of fluorescence intensity, at excitation/emission of 240-520/290-530 nm, were used to identify the wavelengths of interest. RESULTS: Fluorescence excitation/emission maps exhibited two distinct excitation/emission bands whose intensities increased as the fibroblasts remodeled and increased the stiffness of the ECM: The 290/340 nm band ascribed to tryptophan and the 330/390 nm band ascribed to cross-links of collagen (pepsin digestible cross-links). A Spearman correlation analysis, between the elastic modulus of the gel containing fibroblasts and the fluorescence of cross-links of collagen, resulted in R = 0.95 (P < 0.05) and R = 0.77 (P = 0.12) for 50,000 and 100,000 cells/ml, respectively. CONCLUSIONS: The endogenous fluorescence intensity ascribed to pepsin-digestible cross-links of collagen may serve as an optical marker to evaluate changes in the mechanical properties of the ECM; this is relevant to collagenous tissues for which pathological states are related to mechanical alterations, such as keratoconus in cornea and osteoarthritis in articular cartilage. PMID- 26990876 TI - The Confinement-Escape Problem of a Defender Against an Evader Escaping from a Circular Region. AB - In this paper, we first formulate the confinement-escape problem of a defender and an evader who attempts escaping from a circular region, which differs from the traditional pursuit-evasion problems. In our setting of the confinement escape problem, the defender is restricted to move and patrol on the circle, trying to prevent possible escape of the evader who is initially located inside the circle. We describe and characterize some general properties of the problem, and then design two bio-inspired control strategies for the evader and the defender, respectively. In addition, we illustrate some possible motion patterns of the system, investigate the escaping time as a function of the relative initial-positions of the agents, as well as the winning sets of the two players, respectively, under different system-parameters. To that end, we characterize the contour lines of the winning sets with their gradient properties. Finally, we indicate the abrupt phase transitions between successful confinement and escaping, revealing the strong sensitivity and nonlinearities of the system under critical conditions. PMID- 26990878 TI - Multidimensional Germanium-Based Materials as Anodes for Lithium-Ion Batteries. AB - Metallic germanium is an ideal anode for lithium-ion batteries (LIBs), owing to its high theoretical capacity (1624 mA h g(-1) ) and low operating voltage. Herein, we highlight recent advances in the development of Ge-based anodes in LIBs, although improvements in their coulombic efficiency (CE), capacity retention, and rate performance are still required. One of the major concerns facing the development of Ge anodes is the controlled formation of microstructures. In this Focus Review, we summarize Ge-based materials with different structural dimensions, that is, zero-dimensional (0D), one-dimensional (1D), two-dimensional (2D), three-dimensional (3D), and even monolithic and macroscale structures. Moreover, the design of Ge-based oxide materials, as an effective route for achieving higher Li-storage capacities and cycling performance, is also discussed. Finally, we briefly summarize new types of Ge based materials, such as ternary germanium oxides, germanium sulfides, and germanium phosphides, and predict that they will bring about a reformation in the field of LIBs. PMID- 26990877 TI - MiR144/451 Expression Is Repressed by RUNX1 During Megakaryopoiesis and Disturbed by RUNX1/ETO. AB - A network of lineage-specific transcription factors and microRNAs tightly regulates differentiation of hematopoietic stem cells along the distinct lineages. Deregulation of this regulatory network contributes to impaired lineage fidelity and leukemogenesis. We found that the hematopoietic master regulator RUNX1 controls the expression of certain microRNAs, of importance during erythroid/megakaryocytic differentiation. In particular, we show that the erythorid miR144/451 cluster is epigenetically repressed by RUNX1 during megakaryopoiesis. Furthermore, the leukemogenic RUNX1/ETO fusion protein transcriptionally represses the miR144/451 pre-microRNA. Thus RUNX1/ETO contributes to increased expression of miR451 target genes and interferes with normal gene expression during differentiation. Furthermore, we observed that inhibition of RUNX1/ETO in Kasumi1 cells and in RUNX1/ETO positive primary acute myeloid leukemia patient samples leads to up-regulation of miR144/451. RUNX1 thus emerges as a key regulator of a microRNA network, driving differentiation at the megakaryocytic/erythroid branching point. The network is disturbed by the leukemogenic RUNX1/ETO fusion product. PMID- 26990880 TI - Human Papillomavirus-Related Oropharyngeal Cancer in Women. AB - The number of women diagnosed with oropharyngeal cancer related to the human papillomavirus (HPV) is increasing in the United States. Educating health care providers and women about the link between HPV and oropharyngeal cancers can aid in earlier diagnosis and treatment. This article discusses the etiology and clinical presentation of HPV-positive and HPV-negative oropharyngeal cancer, noting distinctions between the 2 types. Recommendations for screening and prevention are provided. PMID- 26990879 TI - Are Additional Tests Needed to Rule Out Axial Spondyloarthritis in Patients Ages 16-45 Years With Short-Duration Chronic Back Pain and Maximally One Spondyloarthritis Feature? AB - OBJECTIVE: To investigate whether HLA-B27 testing and imaging of the sacroiliac joints are needed in patients with <=1 spondyloarthritis (SpA) feature, referred to a secondary care setting, after medical history collection, clinical examination, and measurement of acute phase reactants. METHODS: Baseline data from patients in the Spondyloarthritis Caught Early (SPACE) cohort visiting the rheumatology outpatient clinic of 5 centers across Europe (with back pain >=3 months, <=2 years, onset at ages <45 years) were used. All patients underwent a full diagnostic work-up: magnetic resonance imaging (MRI) and radiographs of the sacroiliac joints, HLA-B27 testing, and assessment of all other SpA features. Patients were diagnosed according to the treating rheumatologist and classified according to the Assessment of SpondyloArthritis international Society (ASAS) axial SpA criteria. RESULTS: Of the 354 patients, 133 (37.5%) showed 0 or 1 SpA feature after medical history collection, physical examination, and measurement of acute phase reactants (38 without SpA features, 95 with 1 SpA feature). Of the patients with <=1 SpA feature, 18.4% (with 0 SpA features) and 17.9% (with 1 SpA feature) were diagnosed with axial SpA according to the rheumatologist after additional investigations (HLA-B27 testing and sacroiliac joint imaging). Additionally, 4 of 38 patients (10.5%) without SpA features fulfilled the ASAS axial SpA criteria (all according to the imaging arm only: 2 as MRI+/modified New York criteria (mNY)+, 1 as MRI+/mNY-, and 1 as MRI-/mNY+). Of the 95 patients with 1 SpA feature, 22 (23.2%) fulfilled the ASAS axial SpA criteria (all according to the imaging arm only: 3 as MRI+/mNY+, 15 as MRI+/mNY-, and 4 as MRI /mNY+). CONCLUSION: In these patients in a secondary care setting with <=1 SpA feature, axial SpA could not be ruled out without sacroiliac joint imaging and/or HLA-B27 testing. PMID- 26990881 TI - The local treatment modalities in FIGO stage I-II small-cell carcinoma of the cervix are determined by disease stage and lymph node status. AB - The purpose of this study was to identify the optimal local treatment modalities for International Federation of Gynecology and Obstetrics (FIGO) stage I-II small cell carcinoma of the cervix (SCCC), including cancer-directed surgery (CDS) and/or radiotherapy (RT). The Surveillance Epidemiology and End Results (SEER) database was used to identify SCCC patients from 1988 to 2012, and analyzed using Kaplan-Meier survival and Cox regression proportional hazard methods to determine factors significant for cause-specific survival (CSS) and overall (OS). A total of 208 patients of SCCC were enrolled. The median follow-up time was 31 months. Fifty-eight (27.9%) patients were treated with primary CDS, 88 (42.3%) patients underwent CDS combined with RT, and 62 (29.8%) patients were treated with primary RT. Univariate and multivariate analyses showed that local treatment modalities were independent prognostic factors for CSS and OS. Patients who had undergone CDS had better CSS and OS, compared with patients who had been treated with combined CDS and RT or RT alone. The 5-year CSS and OS of entire group was 49.8% and 46.4%, respectively. The 5-year CSS in the groups of patients receiving CDS, CDS combined with RT, and RT alone were 67.9%, 49.7%, and 32.6%, respectively (P < 0.001). The 5-year OS in patients treated with CDS, CDS combined with RT, and RT alone were 64.9%, 46.2%, and 28.8% (P < 0.001). Primary surgery was associated with improved CSS and OS for FIGO stage I and lymph node negative disease. Primary surgery is the most effective local treatment for FIGO stage I-II SCCC, as adjuvant RT or radical RT does not improve survival compared to radical surgery, especially in patients with FIGO stage I and lymph node negative disease. PMID- 26990882 TI - Chronic mitragynine (kratom) enhances punishment resistance in natural reward seeking and impairs place learning in mice. AB - Kratom (Mitragyna speciosa) is a widely abused herbal drug preparation in Southeast Asia. It is often consumed as a substitute for heroin, but imposing itself unknown harms and addictive burdens. Mitragynine is the major psychostimulant constituent of kratom that has recently been reported to induce morphine-like behavioural and cognitive effects in rodents. The effects of chronic consumption on non-drug related behaviours are still unclear. In the present study, we investigated the effects of chronic mitragynine treatment on spontaneous activity, reward-related behaviour and cognition in mice in an IntelliCage(r) system, and compared them with those of morphine and Delta-9 tetrahydrocannabinol (THC). We found that chronic mitragynine treatment significantly potentiated horizontal exploratory activity. It enhanced spontaneous sucrose preference and also its persistence when the preference had aversive consequences. Furthermore, mitragynine impaired place learning and its reversal. Thereby, mitragynine effects closely resembled that of morphine and THC sensitisation. These findings suggest that chronic mitragynine exposure enhances spontaneous locomotor activity and the preference for natural rewards, but impairs learning and memory. These findings confirm pleiotropic effects of mitragynine (kratom) on human lifestyle, but may also support the recognition of the drug's harm potential. PMID- 26990883 TI - Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure. AB - Growth hormone (GH) signaling stimulates the production of IGF-1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high-fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet-induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD. PMID- 26990885 TI - Small Titanium Oxo Clusters: Primary Structures of Titanium(IV) in Water. AB - For sol-gel synthesis of titanium oxide, the titanium(IV) precursors are dissolved in water to form clear solutions. However, the solution status of titanium(IV) remains unclear. Herein three new and rare types of titanium oxo clusters are isolated from aqueous solutions of TiOSO4 and TiCl4 without using organic ligands. Our results indicate that titanium(IV) is readily hydrolyzed into oxo oligomers even in highly acidic solutions. The present clusters provide precise structural information for future characterization of the solution species and structural evolution of titanium(IV) in water and, meanwhile, are new molecular materials for photocatalysis. PMID- 26990886 TI - Calcium channels in chicken sperm regulate motility and the acrosome reaction. AB - Intracellular cytoplasmic calcium ([Ca(2+) ]i ) has an important regulatory role in gamete functions. However, the biochemical components involved in Ca(2+) transport are still unknown in birds, an animal class that has lost functional sperm-specific CatSper channels. Here, we provide evidence for the presence and expression of various Ca(2+) channels in chicken sperm, including high voltage activated channels (L and R types), the store-operated Ca(2+) channel (SOC) component Orai1, the transient receptor potential channel (TRPC1) and inositol 1,4,5-trisphosphate receptors (IP3 R1). L- and R-type channels were mainly localized in the acrosome and the midpiece, and T-type channels were not detected in chicken sperm. Orai1 was found in all compartments, but with a weak, diffuse signal in the flagellum. TRCP1 was mainly localized in the acrosome and the midpiece, but a weak diffuse signal was also observed in the nucleus and the flagellum. IP3 R1 was mainly detected in the nucleus. The L-type channel inhibitor nifedipine, the R-type channel inhibitor SNX-482 and the SOC inhibitors MRS-1845, 2-APB and YM-58483 decreased [Ca(2+) ]i sperm motility and acrosome reaction capability, with the SOC inhibitors inhibiting these functions most efficiently. Furthermore, we showed that Ca(2+) -mediated induction of AMP activated protein kinase (AMPK) phosphorylation was blocked by SOC inhibition. Our identification of important regulators of Ca(2+) signaling in avian sperm suggests that SOCs play a predominant role in gamete function, whereas T-type channels may not be involved. In addition, Ca(2+) entry via SOCs appears to be the most likely pathway for AMPK activation and energy-requiring sperm functions such as motility and the acrosome reaction. PMID- 26990887 TI - A General, Concise Strategy that Enables Collective Total Syntheses of over 50 Protoberberine and Five Aporhoeadane Alkaloids within Four to Eight Steps. AB - A concise, catalytic, and general strategy that allowed efficient total syntheses of 22 natural 13-methylprotoberberines within four steps for each molecule is reported. This synthesis represents the most efficient and shortest route to date, featuring three catalytic processes: CuI-catalyzed redox-A(3) reaction, Pd catalyzed reductive carbocyclization, and PtO2 -catalyzed hydrogenation. Importantly, this new strategy to the tetracyclic framework has also been applied to the collective concise syntheses of >30 natural protoberberines (without 13 methyl group) and five aporhoeadane alkaloids. PMID- 26990889 TI - The significance of Delphian lymph node in papillary thyroid cancer. AB - AIM: To investigate the clinical significance of the DLN metastasis in papillary thyroid cancer (PTC). METHODS: A total of 231 PTC patients who underwent first surgical treatment in the Department of Hand and Neck Surgery of Zhejiang Cancer Hospital from January 2013 to June 2014 were enrolled. The relationship between Delphian lymph node (DLN) metastasis and patient age, gender, tumor size, tumor number, unilateral or bilateral, capsular invasion, pretracheal and paratracheal node metastasis, and lateral node metastasis was analyzed. RESULTS: Within 231 cases, 69 showed DLN, but only 19 (8.23%) were found with metastasis. In the univariate analysis, DLN metastasis was significantly associated with tumor size (P = 0.023), capsular invasion (P = 0.001), pretracheal or paratracheal node metastasis (P = 0.003) and lateral node metastasis (P = 0.001), while there were no significant correlation between DLN metastasis and gender (P = 0.976), age (P = 0.976), tumor number (P = 0.234) and unilateral or bilateral (P = 0.724). In the multivariate analysis, capsular invasion was an independent risk factor of DLN metastasis (P < 0.05, odds ratio = 10.15). CONCLUSION: Capsular invasion is an independent risk factor of DLN metastasis and DLN metastasis could be used as a predictor of lateral node metastasis. The dissection of DLN in PTC patients is recommended and lateral lymph node should be evaluated for patients with DLN positive. PMID- 26990884 TI - Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes. AB - OBJECTIVE: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. METHODS: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. RESULTS AND INTERPRETATION: We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions. PMID- 26990890 TI - In Vitro Expression of the Extracellular Matrix Components Aggrecan, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes. AB - The extracellular matrix (ECM) of hyaline cartilage is perfectly suited to transmit articular pressure load to the subchondral bone. Pressure is transferred by a high amount of aggrecan-based proteoglycans and collagen type II fibres in particular. After any injury, the hyaline cartilage is replaced by fibrocartilage, which is low in proteoglycans and contains collagen type I predominantly. Until now, long-term results of therapeutic procedures including cell-based therapies like autologous chondrocyte transplantation (ACT) lead to a replacement tissue meeting the composition of fibrocartilage. Therefore, it is of particular interest to discover how and to what extent isolation and in vitro cultivation of chondrocytes affect the cells and their expression of ECM components. Hyaline cartilage-derived chondrocytes were cultivated in vitro and observed microscopically over a time period of 35 days. The expression of collagen type I, collagen type II and aggrecan was analysed using RT-qPCR and Western blot at several days of cultivation. Chondrocytes presented a longitudinal shape for the entire cultivation period. While expression of collagen type I prevailed within the first days, only prolonged cultivation led to an increase in collagen type II and aggrecan expression. The results indicate that chondrocyte isolation and in vitro cultivation lead to a dedifferentiation at least to the stage of chondroprogenitor cells. PMID- 26990888 TI - The impact of crystallization conditions on structure-based drug design: A case study on the methylene blue/acetylcholinesterase complex. AB - Structure-based drug design utilizes apoprotein or complex structures retrieved from the PDB. >57% of crystallographic PDB entries were obtained with polyethylene glycols (PEGs) as precipitant and/or as cryoprotectant, but <6% of these report presence of individual ethyleneglycol oligomers. We report a case in which ethyleneglycol oligomers' presence in a crystal structure markedly affected the bound ligand's position. Specifically, we compared the positions of methylene blue and decamethonium in acetylcholinesterase complexes obtained using isomorphous crystals precipitated with PEG200 or ammonium sulfate. The ligands' positions within the active-site gorge in complexes obtained using PEG200 are influenced by presence of ethyleneglycol oligomers in both cases bound to W84 at the gorge's bottom, preventing interaction of the ligand's proximal quaternary group with its indole. Consequently, both ligands are ~3.0A further up the gorge than in complexes obtained using crystals precipitated with ammonium sulfate, in which the quaternary groups make direct pi-cation interactions with the indole. These findings have implications for structure-based drug design, since data for ligand-protein complexes with polyethylene glycol as precipitant may not reflect the ligand's position in its absence, and could result in selecting incorrect drug discovery leads. Docking methylene blue into the structure obtained with PEG200, but omitting the ethyleneglycols, yields results agreeing poorly with the crystal structure; excellent agreement is obtained if they are included. Many proteins display features in which precipitants might lodge. It will be important to investigate presence of precipitants in published crystal structures, and whether it has resulted in misinterpreting electron density maps, adversely affecting drug design. PMID- 26990891 TI - Kawasaki disease in infants below 6 months: a clinical conundrum? AB - AIM: Kawasaki disease (KD) is a medium vessel vasculitis of childhood. In infancy KD is often characterized by incomplete and atypical forms. There is paucity of literature on KD in children below 6 months and there are no data from any developing country. This study defines the profile of children with KD below 6 months at our centre. METHODS: During January 1994 to March 2015, 460 children were diagnosed with KD and 17 (3.6%) were below 6 months. Diagnosis was based on American Heart Association (AHA) criteria. All children were treated with intravenous immunoglobulin and aspirin; three also received infliximab. RESULTS: Mucosal changes were present in 11 patients (64%); extremity changes in 11 (64%); rash in nine (53%); conjunctival injection in eight (47%); and cervical lymphadenopathy in three (17%). Irritability was noted in 15 patients (88%); four (23%) had respiratory symptoms; and two (11%) had bacille Calmette-Guerin scar reactivation. Fifteen (88%) had incomplete KD. Twelve patients were diagnosed beyond day 10 of illness. Thrombocytopenia was seen in four. Coronary artery abnormalities were present in six (35%) patients. Two children died from disease related complications - one of these had giant coronary artery aneurysms. CONCLUSION: Our data show that incomplete forms of KD are commonly seen in children below 6 months of age, thereby resulting in delayed diagnoses. Pediatricians need to have a high index of suspicion of KD when dealing with a young infant with unexplained fever beyond 5 days. The AHA criteria appear to be inadequate for diagnosing KD in infants below 6 months. PMID- 26990892 TI - Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG HD2 trial. AB - The prospective, randomized phase III trial GMMG-HD2 aimed at demonstrating non inferiority of single (Arm A) versus tandem (Arm B) high-dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2-year event-free survival (EFS) in newly-diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention-to-treat population, (ITT), single/tandem HDM/ASCT: n = 177/181]. After a median follow-up of more than 11 years, non-inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non-inferiority threshold of 15% of the 2-year EFS rate. Neither EFS (P = 0.53) nor overall survival (OS) (P = 0.33) differences were observed in the ITT population. In the tandem arm, 26% (n = 47/181) of patients refused a second HDM/ASCT due to non medical reasons. A per-protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n = 156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n = 22/181), did not yield differences in EFS (P = 0.61) or OS (P = 0.16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P = 0.04). Ten-year OS for the entire ITT was 34% (95% confidence interval: 29-40%). OS after first relapse was significantly shortened in the tandem arm (P = 0.04). In this study single HDM/ASCT was non-inferior to tandem HDM/ASCT in MM. PMID- 26990893 TI - Simple renal cysts in the solitary kidney: Are they innocent in adult patients? AB - : In patients with a solitary kidney; residual renal volume is an important prognostic factor for kidney survival. At present, the impact of renal cysts on solitary kidney survival is not clear. The aim of this study is to examine the association of cysts on progression of renal failure in patients with a solitary kidney. METHODS: This study included sixtyfive solitary kidney patients. The remaining kidneys after indication nephrectomy (IN) were evaluated with urinary system ultrasound. The primary outcome of the study is the progression of kidney failure during follow-up which was defined as: 25% decrease in glomerular filtration rate (GFR) and / or the need for renal replacement therapy (RRT). RESULTS: The mean age of the patients was 55 +/- 14 years and mean follow-up was 53 +/- 27 months. Renal cysts were present in 30.7% of patients. 33.8 percent of patients had kidney disease progression and 10.7 % required RRT. Those with progressive disease were older (61 +/- 13, 52 +/- 14; P = 0.011), had lower baseline GFR (30 +/- 11, 39 +/- 18; P = 0.035), higher proteiuria (2.84 +/- 0.58, 2.47 +/- 0.57; P = 0.031) and frequently harboring cysts in the solitary kidney (52.3%, 20.4%; P = 0.006). Progression to kidney failure and RRT requirement in cases with or without renal cysts was (60% vs. 22%; P = 0.004) and (20% vs. 6.6%; P = 0.123), respectively. Acquired cysts in solitary kidney was independently associated with progression to kidney failure and RRT respectively (Exp(B) 3.173; P = 0.01 and Exp(B) 12.35; P = 0.04). CONCLUSION: Simple renal cysts in solitary kidney patients with impaired renal function is associated with poor renal outcome. Large-scale studies are needed to clarify this issue. PMID- 26990894 TI - GARP inhibits allergic airway inflammation in a humanized mouse model. AB - BACKGROUND: Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. METHODS: To analyze the therapeutic effects of sGARP, adult NOD/Scidgammac(-/-) (NSG) mice received peripheral blood mononuclear cells (PBMC) derived from allergic patients with sensitization against birch allergen. Subsequently, allergic inflammation was induced in the presence of Treg alone or in combination with sGARP. RESULTS: In comparison with mice that received Treg alone, additional treatment with sGARP reduced airway hyperresponsiveness (AHR), influx of neutrophils and macrophages into the bronchoalveolar lavage (BAL), and human CD45(+) cells in the lungs. Furthermore, the numbers of mucus-producing goblet cells and inflammatory cell infiltrates were reduced. To elucidate whether the mechanism of action of sGARP involves the TGF-beta receptor pathway, mice additionally received anti-TGF-beta receptor II (TGF-betaRII) antibodies. Blocking the signaling of TGF-beta through TGF-betaRII abrogated the anti inflammatory effects of sGARP, confirming its essential role in inhibiting the allergic inflammation. CONCLUSION: Induction of peripheral tolerance via sGARP is a promising potential approach to treat allergic airway diseases. PMID- 26990895 TI - The reversed paradigm of chimerism induction: Donor conditioning with recipient derived bone marrow cells as a novel approach for tolerance induction in vascularized composite allotransplantation. AB - PURPOSE: To test a new approach of donor conditioning with recipient bone marrow cells (BMC) to induce tolerance in vascularized composite allograft (VCA) transplantation. METHODS: Lewis rats' (recipients) BMC were stained with PKH-26. The ACI rats (donors) were conditioned with 80 * 106 Lewis BMC, 24 or 72 hours before VCA (groin flap) transplantation. Forty-eight VCA were performed between ACI donors and Lewis recipients. In groups I and II, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received 7 day anti-alphabeta-TCR/cyclosporine-A post-transplantation. In groups III and IV, donors were preconditioned (24 and 72 hours before transplantation, respectively), and recipients received no systemic immunosuppression. In group V, recipients received 7-day anti-alphabeta-TCR/cyclosporine-A post-transplantation. In group VI, recipients received no systemic immunosuppression. Assessment included evaluation of transplant viability and induction of donor-specific chimerism via flow cytometry, immunofluorescence, and PCR. RESULTS: Groups III, IV, and VI rejected allografts, at an average of 14 +/- 5.2, 10 +/- 2.7, and 8 +/ 0.7 days. In groups I, II, and V, the mean survival was 80 +/- 18.2 (p = 0.0002), 64 +/- 27.4 (p = 0.001), and 30 +/- 4.7 (p = 0.02) days. In groups I and II, donor-specific chimerism in the blood decreased from 8.8 +/- 3.4% and 8.6 +/- 3.4% on day 7 to 3.7 +/- 1.32% (p = 0.02) and 4.7 +/- 2.7% when the flaps manifested grade 3 rejection. The presence of PKH-26+ Lewis BMC was confirmed in the donor's blood, bone marrow, lymphoid organs, and liver (preconditioned at 24 and 72 hours). CONCLUSIONS: Donor preconditioning is a novel approach modifying recipient's responsiveness to donor allograft and prolonging the allograft survival under short-term immunosuppression. (c) 2015 Wiley Periodicals, Inc. Microsurgery 36:676-683, 2016. PMID- 26990896 TI - BODYGUARD is required for the biosynthesis of cutin in Arabidopsis. AB - The cuticle plays a critical role in plant survival during extreme drought conditions. There are, however, surprisingly, many gaps in our understanding of cuticle biosynthesis. An Arabidopsis thaliana T-DNA mutant library was screened for mutants with enhanced transpiration using a simple condensation spot method. Five mutants, named cool breath (cb), were isolated. The cb5 mutant was found to be allelic to bodyguard (bdg), which is affected in an alpha/beta-hydrolase fold protein important for cuticle structure. The analysis of cuticle components in cb5 (renamed as bdg-6) and another T-DNA mutant allele (bdg-7) revealed no impairment in wax synthesis, but a strong decrease in total cutin monomer load in young leaves and flowers. Root suberin content was also reduced. Overexpression of BDG increased total leaf cutin monomer content nearly four times by affecting preferentially C18 polyunsaturated omega-OH fatty acids and dicarboxylic acids. Whole-plant gas exchange analysis showed that bdg-6 had higher cuticular conductance and rate of transpiration; however, plant lines overexpressing BDG resembled the wild-type with regard to these characteristics. This study identifies BDG as an important component of the cutin biosynthesis machinery in Arabidopsis. We also show that, using BDG, cutin can be greatly modified without altering the cuticular water barrier properties and transpiration. PMID- 26990897 TI - Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro. AB - Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon gamma, and decreased levels of interleukin-10 and tumor growth factor-beta in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC mediated immune response. Notably, exosomes from HCC cells not only promoted HCC specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types. CONCLUSION: HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472). PMID- 26990898 TI - Better-surviving barn swallow mothers produce more and better-surviving sons. AB - Sex allocation theory predicts that parents are selected to bias their progeny sex ratio (SR) toward the sex that will benefit the most from parental quality. Because parental quality may differentially affect survival of sons and daughters, a pivotal test of the adaptive value of SR adjustment is whether parents overproduce offspring of the sex that accrues larger fitness advantages from high parental quality. However, this crucial test of the long-term fitness consequences of sex allocation decisions has seldom been performed. In this study of the barn swallow (Hirundo rustica), we showed a positive correlation between the proportion of sons and maternal annual survival. We then experimentally demonstrated that this association did not depend on the differential costs of rearing offspring of either sex. Finally, we showed that maternal lifespan positively predicted lifespan of sons but not of daughters. Because in barn swallows lifespan is a strong determinant of lifetime reproductive success, the results suggest that mothers overproduce offspring of the sex that benefits the most from maternal quality. Hence, irrespective of mechanisms causing the SR bias and mother-son covariation in lifespan, we provide strong evidence that sex allocation decisions of mothers can highly impact on their lifetime fitness. PMID- 26990899 TI - Telemedicine Provides Noninferior Research Informed Consent for Remote Study Enrollment: A Randomized Controlled Trial. AB - OBJECTIVE: Telemedicine networks are beginning to provide an avenue for conducting emergency medicine research, but using telemedicine to recruit participants for clinical trials has not been validated. The goal of this consent study was to determine whether patient comprehension of telemedicine-enabled research informed consent is noninferior to standard face-to-face (F2F) research informed consent. METHODS: A prospective, open-label randomized controlled trial was performed in a 60,000-visit Midwestern academic emergency department (ED) to test whether telemedicine-enabled research informed consent provided noninferior comprehension compared with standard consent. This study was conducted as part of a parent clinical trial evaluating the effectiveness of 0.12% oral chlorhexidine gluconate in preventing hospital-acquired pneumonia among adult ED patients with expected hospital admission. Prior to being recruited into the study, potential participants were randomized in a 1:1 allocation ratio to consent by telemedicine versus standard F2F consent. Telemedicine connectivity was provided using a commercially available interface (REACH platform, Vidyo Inc.) to an emergency physician located in another part of the ED. Comprehension of research consent (primary outcome) was measured using the modified quality of informed consent (QuIC) instrument, a validated tool for measuring research informed consent comprehension. Parent trial accrual rate and qualitative survey data were secondary outcomes. RESULTS: A total of 131 patients were randomized (n = 64, telemedicine), and 101 QuIC surveys were completed. Comprehension of research informed consent using telemedicine was not inferior to F2F consent (QuIC scores 74.4 +/- 8.1 vs. 74.4 +/- 6.9 on a 100-point scale, p = 0.999). Subjective understanding of consent (p = 0.194) and parent trial study accrual rates (56% vs. 69%, p = 0.142) were similar. CONCLUSION: Telemedicine is noninferior to F2F consent for delivering research informed consent, with no detected differences in comprehension and patient-reported understanding. This consent study will inform design of future telemedicine-enabled clinical trials. PMID- 26990900 TI - Comparison of a New and Rapid Method: Brucella Coombs Gel Test With Other Diagnostic Tests. AB - BACKGROUND: The aim of this study was to detect reliability of Brucella Coombs gel test (BCGT) by comparing with with ELISA (IgG + IgM), Standard agglutination test, and Brucella immunocapture agglutination methods in serological diagnosis of brucellosis. METHODS: Brucella Coombs gel test (BCGT), Brucella ELISA (IgG + IgM), Standard agglutination test, and Brucella immunocapture agglutination tests of 78 patients with presumptive diagnosis of brucellosis which were sent to Microbiology Laboratory of Konya Numune Hospital from various regions of Konya were studied. RESULTS: RESULTS: Of 78 patients with ELISA IgG and IgM, STA, BICA and BCGT; 26, 21, 10, 12 and 12 were positive. When compared with BICA, the sensitivity and specifity of BCGT were 100% and 100%, respectively. CONCLUSION: According to results BCGT can be used as a diagnostic test in routine laboratories after more comprehensive studies in control groups and patients. PMID- 26990901 TI - Evidence that some long-lasting effects of direct current in the rat spinal cord are activity-independent. AB - The effects of trans-spinal direct current (DC) stimulation (tsDCS) on specific neuronal populations are difficult to elucidate, as it affects a variety of neuronal networks. However, facilitatory and depressive effects on neurons processing information from the skin and from muscles can be evaluated separately when weak (0.2-0.3 MUA) DC is applied within restricted areas of the rat spinal cord. The effects of such local DC application were recently demonstrated to persist for at least 1 h, and to include changes in the excitability of afferent fibres and their synaptic actions. However, whether these effects require activation of afferent fibres in spinal neuronal pathways during DC application, i.e. whether they are activity-dependent or activity-independent, remained an open question. The aim of the present study was to address this question by analysing the effects of local DC application on monosynaptic actions of muscle and skin afferents (extracellular field potentials) and afferent fibre excitability. The results revealed that long-lasting post-polarization changes evoked without concomitant activation of afferent fibres replicate changes evoked by stimuli applied during, before and after polarization. The study leads to the conclusion that the reported effects are activity-independent. As this conclusion applies to the local effects of DC application in at least two spinal pathways and to the effects of both cathodal and anodal polarization, it indicates that some of the more widespread effects of trans-spinal and trans-cranial stimulation (both tsDCS and transcranial DC stimulation) may be activity-independent. The results may therefore contribute to the design of more specific DC applications in clinical practice. PMID- 26990903 TI - Neoadjuvant radiotherapy for retroperitoneal sarcoma: A systematic review. AB - BACKGROUND AND OBJECTIVES: The multi-modal treatment of retroperitoneal sarcoma has seen increased use of neoadjuvant radiation. However, its effect on local recurrence and survival remain controversial. We aimed to synthesize and evaluate the literature. METHODS: The review was conducted according the recommendation of the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) group with pre specified inclusion and exclusion criteria. RESULTS: Of 8,701 citations collected, 15 articles reported on 464 patients. The median age was 56 years (45 64). The predominant histological subtypes were liposarcoma (51.54%) and leiomyosarcoma (23.26%). Tumor differentiation composed of 37.1% well-, 12.8% moderate-, 46.0% poorly-, and 4.1% undifferentiated. Most studies featured external beam radiation therapy (EBRT) treatment regimen with some who included patients treated with IMRT instead. Median follow-up averaged 41.4 months (19-106 months). Median 5-year OS, PFS, and LRR rates were 58%, 71.5%, and 25%. Using the NCI CTCAE, toxicities from Grade 1 (Mild) through Grade 5 (death) were experienced by 18.8%, 10.2%, 16.3%, 0.7%, and 1.6% of patients. CONCLUSIONS: NART is a safe to use for RPS, but its effect toward survival and local control remains unclear. Without randomized control trials, common reporting criteria for pro- and retrospective studies are needed to allow comparison between studies. J. Surg. Oncol. 2016;113:628-634. (c) 2016 Wiley Periodicals, Inc. PMID- 26990902 TI - Triptolide induced cell death through apoptosis and autophagy in murine leukemia WEHI-3 cells in vitro and promoting immune responses in WEHI-3 generated leukemia mice in vivo. AB - Triptolide, a traditional Chinese medicine, obtained from Tripterygium wilfordii Hook F, has anti-inflammatory, antiproliferative, and proapoptotic properties. We investigated the potential efficacy of triptolide on murine leukemia by measuring the triptolide-induced cytotoxicity in murine leukemia WEHI-3 cells in vitro. Results indicated that triptolide induced cell morphological changes and induced cytotoxic effects through G0/G1 phase arrest, induction of apoptosis. Flow cytometric assays showed that triptolide increased the production of reactive oxygen species, Ca2+ release and mitochondrial membrane potential (DeltaPsim ), and activations of caspase-8, -9, and -3. Triptolide increased protein levels of Fas, Fas-L, Bax, cytochrome c, caspase-9, Endo G, Apaf-1, PARP, caspase-3 but reduced levels of AIF, ATF6alpha, ATF6beta, and GRP78 in WEHI-3 cells. Triptolide stimulated autophagy based on an increase in acidic vacuoles, monodansylcadaverine staining for LC-3 expression and increased protein levels of ATG 5, ATG 7, and ATG 12. The in vitro data suggest that the cytotoxic effects of triptolide may involve cross-talk between cross-interaction of apoptosis and autophagy. Normal BALB/c mice were i.p. injected with WEHI-3 cells to generate leukemia and were oral treatment with triptolide at 0, 0.02, and 0.2 mg/kg for 3 weeks then animals were weighted and blood, liver, spleen samples were collected. Results indicated that triptolide did not significantly affect the weights of animal body, spleen and liver of leukemia mice, however, triptolide significant increased the cell populations of T cells (CD3), B cells (CD19), monocytes (CD11b), and macrophage (Mac-3). Furthermore, triptolide increased the phagocytosis of macrophage from peripheral blood mononuclear cells (PBMC) but not effects from peritoneum. Triptolide promoted T and B cell proliferation at 0.02 and 0.2 mg/kg treatment when cells were pretreated with Con A and LPS stimulation, respectively; however, triptolide did not significant affect NK cell activities in vivo. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 550-568, 2017. PMID- 26990904 TI - Dithioacetal Exchange: A New Reversible Reaction for Dynamic Combinatorial Chemistry. AB - Reversibility of dithioacetal bond formation is reported under acidic mild conditions. Its utility for dynamic combinatorial chemistry was explored by combining it with orthogonal disulfide exchange. In such a setup, thiols are positioned at the intersection of both chemistries, constituting a connecting node between temporally separated networks. PMID- 26990905 TI - Plasma-Engraved Co3 O4 Nanosheets with Oxygen Vacancies and High Surface Area for the Oxygen Evolution Reaction. AB - Co3 O4 , which is of mixed valences Co(2+) and Co(3+) , has been extensively investigated as an efficient electrocatalyst for the oxygen evolution reaction (OER). The proper control of Co(2+) /Co(3+) ratio in Co3 O4 could lead to modifications on its electronic and thus catalytic properties. Herein, we designed an efficient Co3 O4 -based OER electrocatalyst by a plasma-engraving strategy, which not only produced higher surface area, but also generated oxygen vacancies on Co3 O4 surface with more Co(2+) formed. The increased surface area ensures the Co3 O4 has more sites for OER, and generated oxygen vacancies on Co3 O4 surface improve the electronic conductivity and create more active defects for OER. Compared to pristine Co3 O4 , the engraved Co3 O4 exhibits a much higher current density and a lower onset potential. The specific activity of the plasma engraved Co3 O4 nanosheets (0.055 mA cm(-2) BET at 1.6 V) is 10 times higher than that of pristine Co3 O4 , which is contributed by the surface oxygen vacancies. PMID- 26990906 TI - A low FODMAP diet in patients with Crohn's disease. PMID- 26990907 TI - Inevitable problems of older people: presurgery information effect on anxiety levels in patients undergoing cataract surgery. AB - AIMS AND OBJECTIVES: This study was to determine the effect of preoperative patient training on the concern level of patients who would be undergoing cataract surgery. BACKGROUND: Cataract is one of the main causes of blindness in the world. Cataract surgery is located among the quite frequently performed surgeries today. DESIGN: This study was an experimental study. METHODS: The subject pool for this research consisted of patients admitted to the Eskisehir Osmangazi University Medical Faculty Hospital Ophthalmology Department for cataract surgery. The sampling consisted of volunteers who were able to communicate and were deemed suitable patients within the limitations of this study (a total of 100 patients; control group = 50, experimental group = 50). Patient identification forms and the State Trait Anxiety Inventory I-II scale were used as data collection tools. RESULTS: The mean State Trait Anxiety Inventory pretest score for the experimental group was significantly higher than the mean final test score (53.30 +/- 7.02 and 27.54 +/- 3.25, respectively, p < 0.05). The mean State Trait Anxiety Inventory pretest score of the control group was 53.82 +/- 7.42 and the mean final test score was 49.22 +/- 13.17; there was no significant difference between these average scores (p > 0.05). However, the mean final test scores of the experimental and control groups were significantly different (p < 0.05). CONCLUSIONS: In the experimental group in this study, informative, educational and planned nursing care had a significant impact on anxiety levels in patients who had cataract surgery. RELEVANCE TO CLINICAL PRACTICE: Although it is not implemented in most hospitals, and implementation in some hospitals is unplanned, systematically planned preoperative education should take place as part of standard nursing practices. PMID- 26990908 TI - "I think they're all basically the same": parents' perceptions of human papilloma virus (HPV) vaccine compared with other adolescent vaccines. AB - BACKGROUND: Human papillomavirus (HPV) vaccination is recommended for routine administration at ages 11-12 years. However, uptake is lower than for other vaccines that are also routinely recommended for adolescents (MCV4 and Tdap). Understanding parental perceptions of HPV vaccine compared with other vaccines may help to inform strategies to increase uptake. METHODS: Parents and caregivers (n = 45) of adolescents ages 10-18 years from a low-income, ethnic minority population participated in a qualitative study. Interviews were transcribed verbatim and coded for emergent themes. RESULTS: Many participants perceived the HPV vaccine to be similar to other routine vaccines. Noted similarities included the vaccines' ability to prevent disease, similar methods of administration and belief in health care providers' recommendation. Some parents noted the greater benefit of HPV vaccine in preventing cancer, which was viewed as a serious disease. Parents also noted the different mode of transmission (sexual) for HPV, which evoked mixed opinions. CONCLUSION: Overall, most participants viewed the HPV vaccine in a positive light and similar to other adolescent vaccines with the added benefit of cancer prevention. Strategies that treat all three vaccines equally such as presenting them similarly as a 'bundle' to parents or considering policy initiatives such as school entry requirements might help increase raise coverage for HPV vaccine. PMID- 26990909 TI - Polydimethyl siloxane based nanocomposites with antibiofilm properties for biomedical applications. AB - Polydimethyl siloxane (PDMS) is an excellent implant material for biomedical applications, but often fails as it is prone to microbial colonization which forms biofilms. In the present study CuO, CTAB capped CuO, and ZnO nanoparticles were tested as nanofillers to enhance the antibiofilm property of PDMS against Staphylococcus aureus and Escherichia coli. In general S. aurues (Gram positive and more hydrophobic) favor PDMS surface than glass while E. coli (Gram negative and more hydrophilic) behaves in a reverse way. Incorporation of nanofillers renders the PDMS surface antibacterial and reduces the attachment of both bacteria. These surfaces are also not cytotoxic nor show any cell damage. Contact angle of the material and the cell surface hydrophobicity influenced the extent of bacterial attachment. Cell viability in biofilms was dependent on the antimicrobial property of the nanoparticles incorporated in the PDMS matrix. Simple regression relationships were able to predict the bacterial attachment and number of dead cells on these nanocomposites. Among the nanocomposites tested, PDMS incorporated with CTAB (cetyl trimethylammonium bromide)-capped CuO appears to be the best antibacterial material with good cyto-compatibility. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1075 1082, 2017. PMID- 26990911 TI - Validation of a headspace trap gas chromatography and mass spectrometry method for the quantitative analysis of volatile compounds from degraded rapeseed oil. AB - Due to lipid oxidation, off-flavors, characterized by a fishy odor, are emitted during the heating of rapeseed oil in a fryer and affect the flavor of rapeseed oil even at low concentrations. Thus, there is a need for analytical methods to identify and quantify these products. To study the headspace composition of degraded rapeseed oil, and more specifically the compounds responsible for the fishy odor, a headspace trap gas chromatography with mass spectrometry method was developed and validated. Six volatile compounds formed during the degradation of rapeseed oil were quantified: 1-penten-3-one, (Z)-4-heptenal, hexanal, nonanal, (E,E)-heptadienal, and (E)-2-heptenal. Validation using accuracy profiles allowed us to determine the valid ranges of concentrations for each compound, with acceptance limits of 40% and tolerance limits of 80%. This method was then successfully applied to real samples of degraded oils. PMID- 26990910 TI - The involvement of protein kinase G inhibitor in regulation of apoptosis and autophagy markers in spatial memory deficit induced by Abeta. AB - The role of nitric oxide/protein kinase G (NO/PKG) in neurodegenerative disorders is controversial in different circumstances. PKG affects neurons both by itself and as a result of increased NO concentration. In this study, we examined the influence of PKG on spatial memory by intrahippocampal administration of three different concentrations of KT5823 as a PKG inhibitor. Morris water maze (MWM) was used for evaluation of behavioral alterations. We also measured the apoptosis and autophagy markers as two probable interfering pathways with PKG signaling by Western blot method. We found that in Abeta-pretreated rats, intrahippocampus infusions of 2.5, 5, and 10 MUm/side of KT5823 led to a significant reduction in escape latency and traveled distance comparing to Abeta-treatment group. Our molecular findings indicated that KT5823 could induce autophagy and attenuate apoptotic markers at distinct doses. Here, we can conclude that in addition to other parameters, apoptosis, and autophagy in part have damaging and protective roles, respectively, in PKG signaling mechanisms. As autophagy-related proteins lose their functions in neurodegenerative diseases, we can suggest that autophagy can be one of the therapeutic aims for remedy of Alzheimer's disease. PMID- 26990912 TI - Comparison of topically applied flurbiprofen or bromfenac ophthalmic solution on post-operative ocular hypertension in canine patients following cataract surgery. AB - OBJECTIVE: To compare the prevalence and kinetics of ocular hypertension after routine cataract extraction when using a predominately COX-2 inhibitor (bromfenac) versus a predominately COX-1 inhibitor (flurbiprofen) in combination with a topical corticosteroid. PROCEDURES: Patients undergoing unilateral or bilateral cataract surgery were randomly assigned to receive flurbiprofen or bromfenac at the day of surgery and continued for 6 weeks postoperatively, along with topical neo poly dexamethasone. No systemic nonsteroidal anti-inflammatory medications were administered before or after surgery. Intraocular pressure was monitored pre and postoperatively. When an IOP of >25 mmHg was detected, therapeutic intervention was performed. RESULTS: Eyes in both treatment groups showed a similar IOP profile with the highest mean IOP occurring two hours postsurgery and slowly declining during the next 6 weeks. However, eyes receiving bromfenac had a higher mean IOP at 2 h post-op (22.1 mmHg) than eyes receiving flurbiprofen (18.8 mmHg) and a slower decrease in IOP in the weeks after surgery. Over the course of the study, a higher percentage of eyes receiving bromfenac had therapy discontinued over concerns of elevated IOP compared to eyes receiving flurbiprofen (bromfenac 23.1% and flurbiprofen 9.8%). On average, the risk of having elevated intraocular pressure with bromfenac is 1.04 times higher than with flurbiprofen. CONCLUSION: Elevated postoperative IOP was observed in both treatment groups; however, bromfenac-treated eyes were more likely to require intervention for elevated IOP. PMID- 26990914 TI - Photoactivity of g-C3 N4 /S-Doped Porous Carbon Composite: Synergistic Effect of Composite Formation. AB - A composite of g-C3 N4 with visible-light photoactive S-doped carbon was synthesized. Synergistic effects in surface chemistry and electrical conductivity, and a decrease in the band gap (Eg , estimated from optical measurements) from 2.91 eV for g-C3 N4 to 2.79 eV for the composite were found. Both the carbon and the composite showed photosensitivity but only the composite revealed a visible-light-driven reduction activity. PMID- 26990913 TI - Cell number and chondrogenesis in human mesenchymal stem cell aggregates is affected by the sulfation level of heparin used as a cell coating. AB - For particular cell-based therapies, it may be required to culture mesenchymal stem cell (MSC) aggregates with growth factors to promote cell proliferation and/or differentiation. Heparin, a negatively charged glycosaminoglycan (GAG) is known to play an important role in sequestration of positively charged growth factors and, when incorporated within cellular aggregates, could be used to promote local availability of growth factors. We have developed a heparin-based cell coating and we believe that the electrostatic interaction between native heparin and the positively charged growth factors will result in (1) higher cell number in response to fibroblast growth factor-2 (FGF-2) and 2) greater chondrogenic differentiation in response to transforming growth factor-beta1 (TGF beta1), compared to a desulfated heparin coating. Results revealed that in the presence of FGF-2, by day 14, heparin-coated MSC aggregates increased in DNA content 8.5 +/- 1.6 fold compared to day 1, which was greater than noncoated and desulfated heparin-coated aggregates. In contrast, when cultured in the presence of TGF-beta1, by day 21, desulfated heparin-coated aggregates upregulated gene expression of collagen II by 86.5 +/- 7.5 fold and collagen X by 37.1 +/- 4.7 fold, which was higher than that recorded in the noncoated and heparin-coated aggregates. These observations indicate that this coating technology represents a versatile platform to design MSC culture systems with pairings of GAGs and growth factors that can be tailored to overcome specific challenges in scale-up and culture for MSC-based therapeutics. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1817-1829, 2016. PMID- 26990917 TI - Atom Tunneling in Chemistry. AB - Quantum mechanical tunneling of atoms is increasingly found to play an important role in many chemical transformations. Experimentally, atom tunneling can be indirectly detected by temperature-independent rate constants at low temperature or by enhanced kinetic isotope effects. In contrast, the influence of tunneling on the reaction rates can be monitored directly through computational investigations. The tunnel effect, for example, changes reaction paths and branching ratios, enables chemical reactions in an astrochemical environment that would be impossible by thermal transition, and influences biochemical processes. PMID- 26990916 TI - FRY site-specific methylation differentiates pancreatic ductal adenocarcinoma from other adenocarcinomas. AB - Adenocarcinoma is a type of cancer that occurs in the glandular cells throughout the body. There are several metastatic adenocarcinoma of unknown primary origin. Currently, there is no highly effective method to differentiate pancreatic ductal adenocarcinoma (PDAC) from other adenocarcinomas. Here, we identified pancreas tissue by site-specific methylation at FRY and found that it can also detect PDAC. The establishment of Combined Bisulphite Restriction Analysis (COBRA) and quantitative real-time PCR techniques of FRY revealed FRY hypermethylation in 21 out of 24 normal pancreatic tissue samples, whereas all other normal tissue samples from thirteen other organs (80 samples) remained totally unmethylated. Similarly in application to PDAC, this marker effectively indicated 25 PDAC among 151 other common adenocarcinomas with values of 100%, 98.7%, 92.6%, and 100% in sensitivity, specificity, positive predictive value and negative predictive value, respectively. In summary, we have demonstrated that this epigenetic site specific marker has high potential for pancreatic tissue identification and can be applied in PDAC diagnosis. PMID- 26990915 TI - Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women. AB - We aimed at evaluating the risk of liver cancer in different levels of HBsAg among Chinese men and women. We carried out a nested case-control study including 363 cases and 3,511 controls in two population-based cohorts in Shanghai. Plasma samples collected at enrollment were quantified for HBsAg levels using the Architect QT assay. Conditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for liver cancer, with adjustment for potential confounders. HBsAg was detected in 6.29% of control subjects overall (7.02% in men and 4.98% in women). HBsAg levels were positively associated with liver cancer risk in a dose-response manner (ptrend < 0.001). Such association showed a significant gender disparity. With increasing levels of HBsAg, liver cancer risks rose more steeply in men than in women. In men, the adjusted ORs increased from 7.27 (95% CI: 3.49-15.15) at the lowest detectable level of HBsAg (5-9 IU/ml) to 7.16 (95% CI: 3.21-15.96), 34.30 (95% CI: 16.94 69.44), and 47.33 (95% CI: 23.50-95.34) at the highest level of HBsAg (>=1,000 IU/ml) compared to those negative for HBsAg. The corresponding ORs were much lower for women, from 1.37 (95% CI: 0.25-7.47), 3.81 (95% CI: 1.09-13.28), 7.36 (95% CI: 2.41-22.46) and 16.86 (95% CI: 7.24-39.27), respectively. HBsAg quantification has potential to distinguish individuals at different risks of liver cancer. Men with the lowest detectable level of HBsAg should still pay attention to their liver cancer risks, but those with a higher level may be given a higher priority in future liver cancer surveillance program. PMID- 26990918 TI - Theoretical and Experimental Study on Boron beta-Diketonate Complexes with Intense Two-Photon-Induced Fluorescence in Solution and in the Solid State. AB - Three boron diketonate chromophores with extended pi-conjugated backbone were prepared and their spectroscopic features were investigated through a combined theoretical/experimental study. It was shown that these complexes, which undergo very large electronic reorganization upon photoexcitation, combine large two photon absorption cross section with an emission energy and quantum efficiency in solution that is strongly dependent on solvent polarity. The strong positive influence of boron complexation on the magnitude of the two-photon absorption was clearly established, and it was shown that the two-photon absorption properties were dominated by the quadrupolar term. For one of the synthesized compounds, intense one- and two-photon-induced solid-state emission (fluorescence quantum yield of 0.65 with maximum wavelength of 610 nm) was obtained as a result of antiparallel J-aggregate crystal packing. PMID- 26990919 TI - Heritability, evolvability, phenotypic plasticity and temporal variation in sperm competition success of Drosophila melanogaster. AB - Sperm-competition success (SCS) is seen as centrally important for evolutionary change: superior fathers sire superior sons and thereby inherit the traits that make them superior. Additional hypotheses, that phenotypic plasticity in SCS and sperm ageing explain variation in paternity, are less considered. Even though various alleles have individually been shown to be correlated with variation in SCS, few studies have addressed the heritability, or evolvability, of overall SCS. Those studies that have addressed found low or no heritability and have not examined evolvability. They have further not excluded phenotypic plasticity, and temporal effects on SCS, despite their known dramatic effects on sperm function. In Drosophila melanogaster, we found that both standard components of sperm competition, sperm defence and sperm offence, showed nonsignificant heritability across several offspring cohorts. Instead, our analysis revealed, for the first time, the existence of phenotypic plasticity in SCS across an extreme environment (5% CO2 ), and an influence of sperm ageing. Evolvability of SCS was substantial for sperm defence but weak for sperm offence. Our results suggest that the paradigm of explaining evolution by sperm competition is more complex and will benefit from further experimental work on the heritability or evolvability of SCS, measuring phenotypic plasticity, and separating the effects of sperm competition and sperm ageing. PMID- 26990921 TI - Arrhythmogenic right-ventricular cardiomyopathy: molecular genetics into clinical practice in the era of next generation sequencing. AB - Sudden death, ventricular arrhythmia and heart failure are common features in arrhythmogenic right-ventricular cardiomyopathy (ARVC), an inheritable heart muscle disease, characterized by clinical and genetic heterogeneity. So far, 13 disease genes have been identified, responsible for around 60% of all ARVC cases. In this review, we summarize the main clinical and pathological aspects of ARVC, focusing on the importance of the genetic testing and the application of the new sequencing techniques referred to next generation sequencing technology. PMID- 26990920 TI - Renal denervation in heart failure with preserved ejection fraction (RDT-PEF): a randomized controlled trial. AB - AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF. METHODS AND RESULTS: In this single-centre, randomized, open-controlled study we included 25 patients with HFpEF [preserved left ventricular (LV) ejection fraction, left atrial (LA) dilatation or LV hypertrophy and raised B type natriuretic peptide (BNP) or echocardiographic assessment of filling pressures]. Patients were randomized (2:1) to RDT with the SymplicityTM catheter or continuing medical therapy. The primary success criterion was not met in that there were no differences between groups at 12 months for Minnesota Living with Heart Failure Questionnaire score, peak oxygen uptake (VO2 ) on exercise, BNP, E/e', LA volume index or LV mass index. A greater proportion of patients improved at 3 months in the RDT group with respect to VO2 peak (56% vs. 13%, P = 0.025) and E/e' (31% vs. 13%, P = 0.04). Change in estimated glomerular filtration rate was comparable between groups. Two patients required plain balloon angioplasty during the RDT procedure to treat renal artery wall oedema. CONCLUSION: This study was terminated early because of difficulties in recruitment and was underpowered to detect whether RD improved the endpoints of quality of life, exercise function, biomarkers, and left heart remodelling. The procedure was safe in patients with HFpEF, although two patients did require intraprocedure renal artery dilatation. PMID- 26990922 TI - MR feature tracking in patients with MRI-conditional pacing systems: The impact of pacing. AB - PURPOSE: To develop feature tracking (FT) software to perform strain analysis on conventional (nontagged) cardiac magnetic resonance imaging (MRI) function images. With the advent of MRI-conditional pacemaker systems, effects of cardiac pacing on myocardial strain can be studied using MR. In this study the impact of pacing on left ventricular (LV) strain was investigated using MR-FT in patients with an MRI-conditional cardiac implantable electronic device (CIED). MATERIALS AND METHODS: FT was performed on 32 1.5T MR studies (16 patients with an MRI conditional CIED and 16 control patients with normal scans). Short- and long-axis steady state free precession (SSFP) cines were used for the FT analysis. Strain was assessed using CVI(42) software (Circle Cardiovascular Imaging, Alberta, Canada). In addition, the intra- and interobserver variability was determined using the intraclass correlation coefficient. RESULTS: Of the 16 patients with an MRI-conditional CIED, five patients were paced during the MRI exam. Despite the occasional presence of susceptibility artifacts induced by the CIED, radial, circumferential, and longitudinal strain parameters could be derived for all patients. Peak radial strain and peak circumferential strain were reduced during pacing when compared to the control group; for radial strain: 20.1 +/- 4.7% vs. 33.1 +/- 6.9%, P < 0.001, and for circumferential strain -7.5 +/- 3.5% vs. -14.9 +/- 3.2%, P < 0.05. Peak strain parameters were reproducible on an intra- and interobserver level. CONCLUSION: MR-FT is feasible in patients with an MRI conditional CIED and can be used to quantify regional wall motion. J. MAGN. RESON. IMAGING 2016;44:964-971. PMID- 26990923 TI - An extremely rare case of complicated appendicitis: in utero appendix with fistula formation. PMID- 26990924 TI - Protecting the Kidney in Liver Transplant Candidates: Practice-Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice. AB - Acute kidney injury (AKI) and chronic kidney disease (CKD) are common in patients awaiting liver transplantation, and both have a marked impact on the perioperative and long-term morbidity and mortality of liver transplant recipients. Consequently, we reviewed the epidemiology of AKI and CKD in patients with end-stage liver disease, highlighted strategies to prevent and manage AKI, evaluated the changing liver transplant waiting list's impact on kidney function, delineated important considerations in simultaneous liver-kidney transplant selection, and projected possible future transplant policy changes and outcomes. This review was assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice and Board of Directors and provides practice-based recommendations for preservation of kidney function in patients with end-stage liver disease. PMID- 26990925 TI - Label-noise resistant logistic regression for functional data classification with an application to Alzheimer's disease study. AB - Alzheimer's disease (AD) is usually diagnosed by clinicians through cognitive and functional performance test with a potential risk of misdiagnosis. Since the progression of AD is known to cause structural changes in the corpus callosum (CC), the CC thickness can be used as a functional covariate in AD classification problem for a diagnosis. However, misclassified class labels negatively impact the classification performance. Motivated by AD-CC association studies, we propose a logistic regression for functional data classification that is robust to misdiagnosis or label noise. Specifically, our logistic regression model is constructed by adopting individual intercepts to functional logistic regression model. This approach enables to indicate which observations are possibly mislabeled and also lead to a robust and efficient classifier. An effective algorithm using MM algorithm provides simple closed-form update formulas. We test our method using synthetic datasets to demonstrate its superiority over an existing method, and apply it to differentiating patients with AD from healthy normals based on CC from MRI. PMID- 26990926 TI - Orally administered conjugated linoleic acid ameliorates allergic dermatitis induced by repeated applications of oxazolone in mice. AB - Conjugated linoleic acid (CLA) is one of the constituents of animal products with possible health benefits such as anti-carcinogenic and anti-obesity effects. In this study, we investigated the immunomodulatory effects of CLA using a mouse model of allergic dermatitis. Mice were orally administered either a CLA mixture containing equal amounts of 9c, 11 t-CLA and 10 t, 12c-CLA, or high linoleic acid safflower oil, and allergic dermatitis was induced on the ear by repeated topical applications of oxazolone. Oral administration of the CLA mixture but not the high linoleic safflower oil attenuated the symptoms of allergic dermatitis in both ear weights and clinical scores. This effect was associated with decreased levels of ear interleukin-4 (IL-4) and plasma immunoglobulin E. The immunomodulatory effects of the CLA isomers were compared by an in vitro cytokine production assay. The results showed that 9c, 11 t-CLA, the most predominant isomer in animal products, significantly inhibited IL-4 and interferon-gamma production from mouse splenocytes with similar potency to 10 t, 12c-CLA. These findings suggest that CLA, a constituent of animal products, has a potentially beneficial effect for amelioration of allergic dermatitis. PMID- 26990927 TI - Construction of an Artificial Ferrimagnetic Lattice by Lithium Ion Insertion into a Neutral Donor/Acceptor Metal-Organic Framework. AB - Construction of a molecular system in which the magnetic lattice exhibits long range order is one of the fundamental goals in materials science. In this study, we demonstrate the artificial construction of a ferrimagnetic lattice by doping electrons into acceptor sites of a neutral donor/acceptor metal-organic framework (D/A-MOF). This doping was achieved by the insertion of Li-ions into the D/A-MOF, which was used as the cathode of a Li-ion battery cell. The neutral D/A-MOF is a layered system composed of a carboxylate-bridged paddlewheel-type diruthenium(II,II) complex as the donor and a TCNQ derivative as the acceptor. The ground state of the neutral form was a magnetically disordered paramagnetic state. Upon discharge of the cell, spontaneous magnetization was induced; the transition temperature was variable. The stability of the magnetically ordered lattice depended on the equilibrium electric potential of the D/A-MOF cathode, which reflected the electron-filling level. PMID- 26990929 TI - Critical View on Electrochemical Impedance Spectroscopy Using the Ferri/Ferrocyanide Redox Couple at Gold Electrodes. AB - Electrochemical or faradaic impedance spectroscopy (EIS) using the ferri/ferrocyanide couple as a redox probe at gold working electrodes was evaluated with respect to its ability to monitor consecutive surface modification steps. As a model reaction, the reversible hybridization and dehybridization of DNA was studied. Thiol-modified single stranded DNA (ssDNA, 20 bases, capture probe) was chemisorbed to a gold electrode and treated with a solution of short thiols to release nonspecifically adsorbed DNA before hybridization with complementary ssDNA (20 bases, target) was carried out. Reversible dehybridization was achieved by intense rinsing with pure water. The experimental procedures were optimized by kinetic surface plasmon resonance (SPR) and quartz crystal microbalance with dissipation (QCM-D) measurements to maximize the increase in reflectivity or decrease in frequency upon hybridization before hybridization/dehybridization was also monitored by EIS. In contrast to SPR and QCM-D, repeatable EIS measurements were not possible at first. Combined SPR/EIS and QCM-D/EIS measurements revealed that during EIS the gold surface is seriously damaged due to the presence of CN(-) ions, which are released from the ferri/ferrocyanide redox probe. Even at optimized experimental conditions, etching the gold electrodes could not be completely suppressed and the repeatability of the EIS measurements was limited. In three out of four experimental runs, only two hybridization/dehybridization steps could be monitored reversibly by EIS. Thereafter etching the gold electrode significantly contributed to the EIS spectra whereas the QCM-D response was still repeatable. Hence great care has to be taken when this technique is used to monitor surface modification at gold electrodes. PMID- 26990930 TI - Prognostic significance of (18)F-FDG PET at diagnosis in patients with soft tissue sarcoma and bone sarcoma; systematic review and meta-analysis. AB - PURPOSE: The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for the survival prognosis in soft tissue sarcoma (STS) and bone sarcoma (BS) is controversial. The objective of this systematic review was to provide an up-to-date and unprecedented summary of the prognostic value of (18)F FDG PET at diagnosis in STS and BS. METHODS: Studies evaluating pre-treatment (18)F-FDG PET for overall survival of STS and BS were systematically searched for in MEDLINE, EMBASE, and Web of Science. Comparative analyses of the pooled hazard ratios (HR) of overall survival were performed between patients with high and low maximum standardised uptake value (SUVmax). The quality of study designs was evaluated using the Newcastle-Ottawa scale (NOS) for quality assessment of cohort studies. P < 0.05 was defined as statistically significant. RESULTS: A total of six studies comprising 514 patients with STS and BS were considered for the meta analysis. The pooled HR for overall survival was 1.22 (95% confidence interval: 1.03-1.46), suggesting that high SUVmax predicts a significantly shorter overall survival period than low SUVmax (P = 0.03). Additional subgroup analyses using patients with STS alone showed that high SUVmax might predict poorer overall survival than low SUVmax (P = 0.004), although only two studies consisting of 96 patients were included. The overall quality of the included studies evaluated by the NOS assessment was adequate. CONCLUSION: (18)F-FDG PET at diagnosis provides a very useful predictive tool for patients with STS and BS. PMID- 26990928 TI - Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques. AB - Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990932 TI - Synthesis of 5,6-Dihydropyrazolo[5,1-a]isoquinolines through Indium(III)-Promoted Halocyclizations of N-Propargylic Sulfonylhydrazones. AB - A novel method for the preparation of 5,6-dihydropyrazolo[5,1-a]isoquinoline via indium(III)-promoted halocyclizations of N-propargylic sulfonylhydrazones has been developed. The pyrazole and 3,4-dihydroisoquinoline moieties were synchronously formed via a cascade cyclization reaction using easily assembled open-chain compounds. The pyrazole and 3,4-dihydroisoquinoline moieties were formed via a cascade cyclization reaction using easily assembled open-chain compounds. PMID- 26990931 TI - Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma: A randomised phase-III study from the Austrian Cancer Drug Therapy Working Group [Arbeitsgemeinschaft Medikamentose Tumortherapie AGMT](NHL-14). AB - BACKGROUND: Chemoimmunotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin may induce early and late cardiotoxicity. Non-pegylated liposomal (NPL) doxorubicin may reduce cardiotoxicity. PATIENTS AND METHODS: Patients with untreated CD20+ DLBCL were randomised to conventional R-CHOP chemoimmunotherapy or rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone (R-COMP) with doxorubicin substituted by NPL-doxorubicin. Left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were measured before each treatment cycle and after the end of treatment. RESULTS: The mean LVEF of 178 and 158 measurements in the R COMP and R-CHOP arms was 63.31% and 62.25%, respectively (P = 0.167). During treatment the LVEF measurements were below 50% in 10/218 (4.6%) in the R-COMP arm and 31/196 (15.8%) in the R-CHOP arm (P<0.001). Thirty-six of 40 (90%) patients in the R-COMP arm, but only 24/36 (66.7%) in the R-CHOP arm had all NT-proBNP levels below 400 pg/ml during and at the end of treatment (P = 0.013). There were more serious adverse events in the R-CHOP arm (26 versus 40, P = 0.029). Infections were more common (15 versus 28) in the R-CHOP arm. INTERPRETATION: In patients with normal cardiac function, six cycles of R-CHOP resulted in a low rate of early cardiotoxicity. NPL-doxorubicin did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP. FUNDING: Cephalon provided the Arbeitsgemeinschaft Medikamentose Tumortherapie with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the paper. PMID- 26990933 TI - Reliability of immunocytochemistry and fluorescence in situ hybridization on fine needle aspiration cytology samples of breast cancers: A comparative study. AB - INTRODUCTION: To characterize breast tumors and metastases, fine-needle aspiration cytology (FNAB) can be a favorable first choice. However, the diagnostic accuracy of ancillary tests applied to FNAB samples is yet to be validated. PATIENTS AND METHODS: We examined 110 breast cancer patients' paired cytological and surgical resection specimens evaluated between 2005 and 2014. Comparison of ER and Her2 immunocytochemical (ICC) and immunohistochemical (IHC) staining and HER2 fluorescence in situ hybridization (FISH) was performed. RESULTS: Significant difference (p < 0.001) and moderate correlation (kappa = 0.446) were noted between results of 97 paired ICC an IHC reactions for ER expression. ICC for ER status had a sensitivity of 75%, specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 38.2%. Significant difference (p = 0.012) and moderate correlation (kappa = 0.541) were found between results of 77 paired ICC an IHC reactions for Her2 expression. The Her2 ICC had a sensitivity of 54%, specificity of 95.4%, PPV of 66.7%, and NPV of 92.6%. The results of FISH carried out on 23 paired samples of FNAB and surgical specimens indicated perfect correlation (kappa = 1.000) and no significant difference (p = 1.000). FISH performed on FNAB has sensitivity, specificity, PPV, and NPV of 100%. CONCLUSION: The correlation of ICC and IHC is moderate regarding ER and Her2 expression of the same tumor. FISH performed on FNAB samples is suitable to categorize primary and metastatic breast cancer in regard of HER2 gene amplification status and can be used as a predictive test in respect of therapies targeting HER2. Diagn. Cytopathol. 2016;44:466-471. (c) 2016 Wiley Periodicals, Inc. PMID- 26990934 TI - [Hearing Loss in a Blind Youth]. PMID- 26990935 TI - [Speech Ability and Psychological Outcome After Treatment of Oral Cancer]. AB - BACKGROUND: In recent years interactions between surgical treatment of oral carcinoma and incidence of anxiety or depression have become a subject of discussions. This prospective study is a comparison between the extent of loss of speech intelligibility and presence of depressive symptoms or anxiety as a result of oral carcinoma. MATERIAL AND METHODS: One year after surgical therapy for oral carcinoma, 90 patients of an average age of 60+/-12 years were examined. Their speech intelligibility degree was measured using standardized automatic speech recognition (word recognition rate, WR). Symptoms of anxiety and depression were detected by use of HAD-Scales (HADS). Next to the relationship between WR and HADS other influential variables related to WR and HADS were statistically evaluated. RESULTS: The WR average was 53.2+/-17.2. Female WR was better than male. The difference between tumor classifications T1 and T4 compared to the WR reached statistical significance. Significant differences were detected between WR and "tumor localization", "graft donor site", "graft morphology", "tongue motility", and "tracheostoma" groups. There was a relationship between tongue motility and graft morphology, graft donor site and tumor localization. HAD Scores in the mean were elevated: HADS-Total=43.3%, HADS-A=43.3% und HADS-D= 51.1%. WR correlates with HADS-D-Subscale, but not with HADS-A-Subscale. CONCLUSION: Communication disorders as a result of neoplasmic orofacial surgery may be related to extent of the treatment and to affective impairments. This should receive attention in the concept of rehabilitation. PMID- 26990936 TI - [Clinical Aspects of Cochlear Implantation in Meniere's Disease and After Labyrinthectomy]. AB - Objective: Due to the natural aging and the loosened CI-implantation criteria more formerly operated Meniere's patients will be supplied with a cochlear implant. However, it raises the question whether an implantation in a previously treated ear is promising. Material and Methods: Based on 2 cases in which we have carried out a CI-implantation, one of them 10 years after transmastoidal labyrinthectomy, and based on the current literature we draw attention to problems and prospects of success. Discussion: Histological studies show only a small ossification of the cochlea after labyrinthectomy. Implanted Meniere's patients have a better speech intelligibility than other CI users. Attacks of rotatory vertigo with tinnitus and fluctuations of hearing after cochlear implantation in Meniere's patients are rare or they are too little described. Conclusion: There is a trend to perform a simultaneous labyrinthectomy and cochlea implantation in Meniere's patients with desabling vertigo which have not responded to drug treatment. A formerly performed transmastoidal labyrinthectomy is not a contraindication for a cochlear implantation. PMID- 26990937 TI - Risk of second primary malignancies among 1537 melanoma patients and risk of second primary melanoma among 52 354 cancer patients in Northern Italy. AB - BACKGROUND: The number of melanoma survivors has been increasing for decades due to early diagnosis and improved survival. These patients have an increased risk of developing a second primary cancer (SPC); also, melanoma is frequently diagnosed among patients firstly diagnosed with an extracutaneous malignancy. OBJECTIVE: We evaluated the risk of developing a SPC among 1537 melanoma patients, and the risk of second primary melanoma (SPM) in 52 354 extracutaneous cancer patients, who were treated at the European Institute of Oncology in Milan, Italy, during 2000-2010. MATERIAL AND METHODS: We calculated standardized incidence ratios (SIR) by applying gender-, age-, year- and region-specific reference rates to the follow-up time accrued between the diagnosis of the first and the second primary malignancies. RESULTS: Seventy-six SPC were diagnosed during a median follow-up of 4 years, of which 49 (64%) during the first 2 years upon melanoma diagnosis. The SIR was increased for cancer of breast (4.10, 95% CI 2.79-6.03), thyroid (4.67, 95% CI 1.94-11.22), brain (6.13, 95% CI 2.30-16.33) and for non-Hodgkin lymphoma (3.12, 95% CI 1.30-7.50). During a median follow-up of 4 years, 127 SPM were diagnosed: thick lesions were less frequent than for melanoma diagnosed as first cancer. The SIR was increased for cancer of breast (5.13, 95%CI 3.91-6.73), thyroid (16.2, 95%CI: 5.22-50.2), head and neck (5.62, 95%CI 1.41-22.50), soft tissue (8.68, 95%CI 2.17-34.70), cervix (12.5, 95% CI 3.14-50.20), kidney (3.19, 95%CI 1.52-6.68), prostate (4.36, 95%CI 2.63-7.24) and acute myeloid leukaemia (6.44, 95%CI 2.42-17.20). CONCLUSIONS: The most likely causes of these associations are the clustering of lifestyle risk factors in the same subgroups of population, mainly on a sociocultural basis and surveillance bias. This raises important questions about how to best follow cancer survivors by avoiding an inefficient use of resources and an excessive medicalization of these patients' lives. PMID- 26990938 TI - The scale epithelium as a novel, non-invasive tool for environmental assessment in fish: Testing exposure to linear alkylbenzene sulfonate. AB - Increasing pollution levels have turned our attention to assessing lethal and sublethal effects of toxic agents using the most informative techniques possible. We must seek non-invasive or non-lethal sampling methods that represent an attractive alternative to traditional techniques of environmental assessment in fish. Detergents are amongst the most common contaminants of water bodies, and LAS (Linear Alkylbenzene Sulfonate) is one of the most used anionic surfactant on the market. Our study analyzed morphological alterations (histological and histochemical) of the scale epithelium of Prochilodus lineatus under exposure to two concentrations of LAS, 3.6mg/L and 0.36mg/L, for a period of 30 days and evaluated at 14, 21 and 30 days. In order to establish morphological analysis of the scale epithelium as a new non-lethal environmental assessment tool that is reliable and comparable to classic methods, the relative sensibility of this technique was compared to a commonly used method of environmental assessment in fish, the estimation of the effects of pollutants upon branchial morphology. Two experiments were carried out, testing animals in tanks, and in individual aquariums. Results of analyses on gill tissue show that exposure to 3.6mg/L of surfactant caused severe damage, including hyperplasia, hypertrophy and fusion at 14 days, with aneurisms at 21 and 30 days; while exposure to 0.36mg/L had lighter effects on the organ, mainly lower incidence of fusion and hyperplasia. Aditionally, scale morphology was altered severely in response to 3.6mg/L of LAS, consistently showing increased mucous and club cell production. Epithelial thickness was the most variable parameter measured. Scale epithelium sensibility has the potential to be a reliable environmental marker for fish species since it has the advantage of being less invasive when compared to traditional methods. However, more studies are required to increase the robustness of the technique before it can be generally applied. PMID- 26990939 TI - Anoxic biodegradation of petroleum hydrocarbons in saline media using denitrifier biogranules. AB - The total petroleum hydrocarbons (TPH) biodegradation was examined using biogranules at different initial TPH concentration and contact time under anoxic condition in saline media. The circular compact biogranules having the average diameter between 2 and 3mm were composed of a dense population of Bacillus spp. capable of biodegrading TPH under anoxic condition in saline media were formed in first step of the study. The biogranules could biodegrade over 99% of the TPH at initial concentration up to 2g/L at the contact time of 22h under anoxic condition in saline media. The maximum TPH biodegradation rate of 2.6 gTPH/gbiomass.d could be obtained at initial TPH concentration of 10g/L. Accordingly, the anoxic biogranulation is a possible and promising technique for high-rate biodegradation of petroleum hydrocarbons in saline media. PMID- 26990940 TI - Bioaccumulation of trace elements in the sandhopper Talitrus saltator (Montagu) from the Ionian sandy coasts of Sicily. AB - The Ionian beaches of Sicily are of particular ecological interest because they include the basin of the largest active volcano in Europe and hosts both sites subject to natural protection constraints, as well as important industrial settlements. Consequently, the possibilities for these areas to become polluted are numerous. The sandhopper Talitrus saltator has proven to be a good bioindicator of contamination by numerous trace metals on some European coasts. Nevertheless, no data are available for the populations inhabiting the shores of the southern Mediterranean. Now, as metal accumulation has been shown to vary intraspecifically, the aim of this study was to evaluate trace metal accumulation in adults of T. saltator inhabiting Ionian coastal areas of Sicily and make an assessment of natural and anthropogenic metal pollution of this strip of coast. We also extended our survey to As, Co, Mo, Se, Sn and V never investigated before in this species. Significant differences in metal concentration among sites were found in both sand samples and amphipod tissues. The highest metal content was observed near the mouth of Simeto, the longest river of Sicily which collects waters coming from the volcanic territory of Mount Etna. The bioaccumulation of Cd, Cu, Hg and Zn in T. saltator is fully confirmed; it is also proven for As and Mo and assumed for Cr, Fe, Mn and V. Our outcomes let us to evaluate the prevailing influence of telluric contamination of the Ionian sandy shores of Sicily by trace metals. We also come to the conclusion that in the northern sites, pollution originates from volcanic emission while anthropogenic influence prevails in the southern ones. PMID- 26990941 TI - The Incidence and Clinical Features of Dual Thyroid Ectopia in Congenital Hypothyroidism. AB - CONTEXT: Congenital hypothyroidism (CH) may arise from dual foci thyroid ectopia. OBJECTIVE: To ascertain the incidence of dual ectopia in CH and compare the phenotype to single ectopia or thyroid agenesis. DESIGN AND SETTING: Single center, retrospective study of babies referred through UK Newborn Bloodspot Screening between 2006 and 2012. PATIENTS: A total of 837 377 babies were screened for CH, with 730 referred for diagnostic confirmation (134 thyroid ectopia, 73 thyroid agenesis). INTERVENTION: Thyroid isotope scans were classified as single or dual ectopia. Biochemical, clinical, and sociodemographic data were collected. MAIN OUTCOME MEASURES: The incidence of thyroid dual ectopia and comparison of clinical parameters with single ectopia and agenesis. RESULTS: Thyroid ectopia occurs with an incidence of 16 per 100 000 births. Twenty-one of 134 (15.7%) babies with thyroid ectopia had dual foci, an incidence of 2.5 per 100 000 births. Dual ectopia infants had lower mean bloodspot TSH compared to single ectopia and agenesis groups (P < .001). On venous sampling, the ectopia group differences were absent, but the difference with the agenesis group remained (TSH, P < .001; free T4, P < .001). There were no between-group differences for gestation, ethnicity, maternal age, or levothyroxine requirements at 12 months. CONCLUSIONS: Thyroid dual ectopia has an incidence of 2.5 per 100 000 births. Early functional activity in the ectopia groups with detectable serum free T4 concentrations is lost at 12 months when T4 requirements are the same as the agenesis group. PMID- 26990943 TI - Measurement of Salivary Cortisone to Assess the Adequacy of Hydrocortisone Replacement. AB - CONTEXT: This Commentary discusses the study of Debono et al (19) and focuses on the potential use of multiple salivary cortisone measurements to evaluate the adequacy of hydrocortisone replacement therapy. Salivary cortisone, typically measured using liquid chromatography-tandem mass spectrometry, accurately reflects plasma free cortisol because of the expression of 11-beta hydroxysteroid dehydrogenase in the salivary gland. Debono et al showed that multiple, sequential salivary cortisone measurements obtained over a 12-hour period correlated with plasma free cortisol in subjects receiving intravenous or oral hydrocortisone (authentic cortisol). CONCLUSIONS: Hopefully, these studies will lead to a simplified protocol with fewer samples for the measurement of salivary cortisone that can reliably assess the adequacy of hydrocortisone replacement in patients with adrenal insufficiency. This protocol has to be cost effective and be feasible to obtain timed salivary samples accurately at home. It would be a significant advance to be able to monitor hydrocortisone replacement therapy with as few as one or two salivary cortisone measurements. PMID- 26990942 TI - Evidence for Increased 5alpha-Reductase Activity During Early Childhood in Daughters of Women With Polycystic Ovary Syndrome. AB - CONTEXT: Polycystic ovary syndrome (PCOS) is a heritable, complex genetic disease. Animal models suggest that androgen exposure at critical developmental stages contributes to disease pathogenesis. We hypothesized that genetic variation resulting in increased androgen production produces the phenotypic features of PCOS by programming during critical developmental periods. Although we have not found evidence for increased in utero androgen levels in cord blood in the daughters of women with PCOS (PCOS-d), target tissue androgen production may be amplified by increased 5alpha-reductase activity analogous to findings in adult affected women. It is possible to noninvasively test this hypothesis by examining urinary steroid metabolites. OBJECTIVE: We performed this study to investigate whether PCOS-d have altered androgen metabolism during early childhood. DESIGN, SETTING, AND PARTICIPANTS: Twenty-one PCOS-d, 1-3 years old, and 36 control girls of comparable age were studied at an academic medical center. MAIN OUTCOME MEASURES: Urinary steroid metabolites were measured by gas chromatography/mass spectrometry. Twenty-four hour steroid excretion rates and precursor to product ratios suggestive of 5alpha-reductase and 11beta hydroxysteroid dehydrogenase activities were calculated. RESULTS: Age did not differ but weight for length Z-scores were higher in PCOS-d compared to control girls (P = .02). PCOS-d had increased 5alpha tetrahydrocortisol:tetrahydrocortisol ratios (P = .04), suggesting increased global 5alpha-reductase activity. There was no evidence for differences in 11beta hydroxysteroid dehydrogenase activity. Steroid metabolite excretion was not correlated with weight. CONCLUSIONS: Our findings suggest that differences in androgen metabolism are present in early childhood in PCOS-d. Increased 5alpha reductase activity could contribute to the development of PCOS by amplifying target tissue androgen action. PMID- 26990945 TI - The impact of a new McDonald's restaurant on eating behaviours and perceptions of local residents: A natural experiment using repeated cross-sectional data. AB - Neighbourhood food environments are posited as an important determinant of eating behaviours; however causality is difficult to establish based on existing studies. Using a natural experiment study design (incorporating repeated cross sectional data), we tested whether the development of a new McDonald's restaurant increased the frequency of consumption of McDonald's products amongst local residents in the suburbs of Tecoma (site of a new McDonald's restaurant development) and Monbulk (control site) in Victoria, Australia. Across both sites, the reported frequency of McDonald's consumption did not change during the follow-up surveys. In the context explored, the development of a new McDonald's restaurant has not resulted in an increased consumption of McDonald's products. PMID- 26990944 TI - Remote vs. local ischaemic preconditioning in the rat heart: infarct limitation, suppression of ischaemic arrhythmia and the role of reactive oxygen species. AB - The unmet clinical need for myocardial salvage during ischaemia-reperfusion injury requires the development of new techniques for myocardial protection. In this study the protective effect of different local ischaemic preconditioning (LIPC) and remote ischaemic preconditioning (RIPC) protocols was compared in the rat model of myocardial ischaemia-reperfusion, using infarct size and ischaemic tachyarrhythmias as end-points. In addition, the hypothesis that there is involvement of reactive oxygen species (ROS) in the protective signalling by RIPC was tested, again in comparison with LIPC. The animals were subjected to 30-min coronary occlusion and 90-min reperfusion. RIPC protocol included either transient infrarenal aortic occlusion (for 5, 15 and 30 min followed by 15-min reperfusion) or 15-min mesenteric artery occlusion with 15-min reperfusion. Ventricular tachyarrhythmias during test ischaemia were quantified according to Lambeth Conventions. It was found that the infarct-limiting effect of RIPC critically depends on the duration of a single episode of remote ischaemia, which fails to protect the heart from infarction when it is too short or, instead, too prolonged. It was also shown that RIPC is ineffective in reducing the incidence and severity of ischaemia-induced ventricular tachyarrhythmias. According to our data, the infarct-limiting effect of LIPC could be partially eliminated by the administration of ROS scavenger N-2-mercaptopropionylglycine (90 mg/kg), whereas the same effect of RIPC seems to be independent of ROS signalling. PMID- 26990947 TI - Rat Blastocysts from Nuclear Injection and Time-Lagged Enucleation and Their Commitment to Embryonic Stem Cells. AB - Pronucleus-like vesicle formation following premature chromosome condensation (PCC) of the donor cell nucleus is the key event for successful generation of cloned rodents by nuclear transplantation (NT). However in rat cloning, this change is difficult to induce in enucleated recipient oocytes because of their inability to maintain maturation-promoting factor levels. In this study, intact oocytes retrieved from nuclear-visualized H2B-tdTomato knock-in rats were injected with Venus-labeled cell nuclei. Because the incidence of PCC under MG 132 treatment significantly increased with the culture period (0%, 10.8%, 36.8%, and 87.5% at 0, 0.5, 1, and 2 h postinjection, respectively), the metaphase plate of the oocyte was removed 1-2 h after the nuclear injection. The NT-derived rat zygotes (n = 748) were activated with ionomycin/cycloheximide and transferred into temporal host mothers, resulting in the harvest of three blastocysts (0.4%) with Venus fluorescence. Two blastocysts were examined for their potential to commit to NT-derived embryonic stem cells (ntESCs). One ntESC line was established successfully and found to be competent in terms of karyotype, stem cell marker expression, and pluripotency. In conclusion, time-lagged enucleation of visualized oocyte nuclei allows the PCC incidence of donor nuclei and generation of NT blastocysts, and the blastocysts can commit to germline competent ntESCs. PMID- 26990949 TI - Praambel. PMID- 26990948 TI - Inhibition of G Protein betagamma Subunit Signaling Abrogates Nephritis in Lupus Prone Mice. AB - OBJECTIVE: Despite considerable advances in the understanding of systemic lupus erythematosus (SLE), there is still an urgent need for new and more targeted treatment approaches. We previously demonstrated that small-molecule blockade of G protein betagamma subunit (Gbetagamma) signaling inhibits acute inflammation through inhibition of chemokine receptor signal transduction. We undertook this study to determine whether inhibition of Gbetagamma signaling ameliorates disease in a mouse model of SLE. METHODS: Lupus-prone (NZB * NZW)F1 female mice were prophylactically or therapeutically treated with the small-molecule Gbetagamma inhibitor gallein. Tissue samples were analyzed by flow cytometry and immunohistochemistry. The development and extent of nephritis were assessed by monitoring proteinuria and by immunohistochemical analysis. Serum immunoglobulin levels were measured by enzyme-linked immunosorbent assay, and total IgG and anti double-stranded DNA (anti-dsDNA) antibody-secreting cells were measured by enzyme linked immunospot assay. RESULTS: Gallein inhibited accumulation of T cells and germinal center (GC) B cells in the spleen. Both prophylactic and therapeutic treatment reduced GC size, decreased antibody-secreting cell production in the spleen, and markedly decreased accumulation of autoreactive anti-dsDNA antibody secreting cells in kidneys. Gallein also reduced immune complex deposition in kidneys. Finally, gallein treatment dramatically inhibited kidney inflammation, prevented glomerular damage, and decreased proteinuria. Mechanistically, gallein inhibited immune cell migration and signaling in response to chemokines in vitro, which suggests that its mechanisms of action in vivo are inhibition of migration of immune cells to sites of inflammation and inhibition of immune cell maturation. CONCLUSION: Overall, these data demonstrate the potential use of gallein or novel inhibitors of Gbetagamma signaling in SLE treatment. PMID- 26990951 TI - Lungenembolie (LE). PMID- 26990950 TI - Bein- und Beckenvenenthrombose (TVT). PMID- 26990952 TI - Literaturverzeichnis. PMID- 26990953 TI - Temperature-driven self-assembly of self-limiting uniform supraparticles from non uniform unimolecular micelles. AB - In this work, the self-assembly of non-uniform unimolecular micelles constituted of a hyperbranched polyester core decorated with a corona of thermoresponsive poly(N-isopropylacrylamide) (PNIPAm) chains has been studied. As revealed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS), these unimicelles form uniform supraparticles through a thermally-induced self-limited process, as well as exhibit molecular features commonly observed in PNIPAm-based gels. We believe that these results provide new insights into the application of stimuli-responsive polymeric materials as versatile building blocks to build up soft supraparticles displaying well-defined dimensional characteristics. PMID- 26990954 TI - Synthesis of Cu2O nanoparticle films at room temperature for solar water splitting. AB - A Cu2O nanoparticle film using ZnO nanorods as a sacrificial scaffold was fabricated near 23 degrees C, for applications in photoelectrochemical (PEC) water splitting. Three chemical solutions were utilized to convert ZnO nanorods to a Cu2O nanoparticle film - solutions of CuCl2 and NaOH, NaBH4 and NaOH, respectively. The structural evolution from ZnO through Cu(OH)2 and metallic Cu to Cu2O phase was analyzed at each stage with X-ray diffraction and X-ray absorption spectra. The energy bandgap was deduced from IPCE; the concentration of carriers and flat-band of a Cu2O nanoparticle film were obtained from a Mott Schottky plot. Significantly, the Cu2O nanoparticle film exhibited a useful PEC response to water oxidation. This nanostructure synthesized with no energy requirement can not only illustrate a great prospect for solar generation of hydrogen but also offer a blueprint for the future design of photocatalysts. PMID- 26990955 TI - Neutron reflectometry of anionic surfactants on sapphire: A strong maximum in the adsorption near the critical micelle concentration. AB - The adsorption of the anionic surfactants, lithium, sodium and cesium dodecylsulfates, and sodium decylsulfonate, on the positively charged C-plane (0001) of sapphire (alumina) has been measured using neutron reflection. For each of the four surfactants there is a strong maximum in the adsorption at about the critical micelle concentration. The maximum becomes more marked from lithium to cesium. The measurements were reproduced over a range of different physical conditions and could not be accounted for in terms of impurities. The maximum is explained quantitatively by using the combination of a mass action model to calculate the mean activity of the surfactant, and a cooperative model of the adsorption (Frumkin), in which saturation of the layer is not attained until well above the critical micelle concentration. PMID- 26990956 TI - Modeling approach for tensile strength of interphase layers in polymer nanocomposites. AB - At the first step, this paper describes a developed model for tensile strength of interphase layers (sigma(k)) in polymer nanocomposites. The "sigma(k)" is expressed as linear, exponential and power functions of the distance between nanoparticles and polymer matrix (x(k)). Afterwards, the predictions of these equations at the central layer of interphase (the average strength) are compared to the calculations of interphase strength (sigma(i)) by several micromechanical models including the developed Leidner-Woodhams and Pukanszky models to choose the best equation which expresses "sigma(k)". The calculations are carried out for several reported samples. The equation which expresses the "sigma(k)" as a power function of "xk" shows the best results compared to others. Also, its predictions significantly depend to an exponent as "Z" which demonstrates the level of interphase properties. According to the chosen equation, the "sigma(m)" and "sigma(p)" play positive roles in "sigma(i)" predictions at low "Z" value, but a high "Z" eliminates the effect of "sigma(m)" on the tensile strength of interphase layers. PMID- 26990958 TI - Genome-wide association scan suggests basis for microtia in Awassi sheep. AB - Hereditary underdevelopment of the ear, a condition also known as microtia, has been observed in several sheep breeds as well as in humans and other species. Its genetic basis in sheep is unknown. The Awassi sheep, a breed native to southwest Asia, carries this phenotype and was targeted for molecular characterization via a genome-wide association study. DNA samples were collected from sheep in Jordan. Eight affected and 12 normal individuals were genotyped with the Illumina OvineSNP50((r)) chip. Multilocus analyses failed to identify any genotypic association. In contrast, a single-locus analysis revealed a statistically significant association (P = 0.012, genome-wide) with a SNP at basepair 34 647 499 on OAR23. This marker is adjacent to the gene encoding transcription factor GATA-6, which has been shown to play a role in many developmental processes, including chondrogenesis. The lack of extended homozygosity in this region suggests a fairly ancient mutation, and the time of occurrence was estimated to be approximately 3000 years ago. Many of the earless sheep breeds may thus share the causative mutation, especially within the subgroup of fat-tailed, wool sheep. PMID- 26990957 TI - Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. AB - BACKGROUND: For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. METHODS: A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Five studies including 1116 patients reported major complications in 25 (4.9 per cent) of 510 patients in the antibiotic and 41 (8.4 per cent) of 489 in the appendicectomy group: risk difference -2.6 (95 per cent c.i. -6.3 to 1.1) per cent (low-quality evidence). Minor complications occurred in 11 (2.2 per cent) of 510 and 61 (12.5 per cent) of 489 patients respectively: risk difference -7.2 (-18.1 to 3.8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8.2 (95 per cent c.i. 5.2 to 11.8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22.6 (15.6 to 30.4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. CONCLUSION: The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value- and preference-dependent, suggesting a change in practice towards shared decision-making is necessary. PMID- 26990959 TI - Contemporary antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: 1-year outcomes from the GReek AntiPlatElet (GRAPE) Registry. AB - Essentials The comparative efficacy and safety of antiplatelet agents in 'real life' is not clear. We recruited acute coronary syndrome patients receiving percutaneous coronary intervention. At 1-year follow-up, prasugrel offers better anti-ischemic protection than clopidogrel. Prasugrel and ticagrelor are accompanied by more frequent bleeding events. SUMMARY: Background The comparative efficacy and safety of antiplatelet treatment outside randomized trials is not clear. Objectives To investigate long-term efficacy and safety in 'real-life' acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with contemporary use of clopidogrel, prasugrel and ticagrelor. Methods In a prospective, observational, multicenter cohort study, 2047 patients were recruited into the GReek AntiPlatElet (GRAPE) Registry and were followed-up for 1 year for major adverse cardiovascular events (MACE, a composite of death, non-fatal myocardial infarction, urgent revascularization and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification). Results Exposure to clopidogrel, prasugrel and ticagrelor by PCI occurred in 959, 363 and 717 patients, respectively. After adjustment, the rate of MACE (primary outcome endpoint) was lower in prasugrel-treated patients (4.4%) than in clopidogrel-treated patients (10.1%) (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.30-0.91), although not significantly different between ticagrelor (6.8%) and clopidogrel groups (HR, 0.78; 95% CI, 0.54-1.12). Any type of BARC-classified bleeding (secondary outcome endpoint) was more frequent in prasugrel-treated patients (51.2%) than in clopidogrel-treated patients (37.6%) (HR, 1.61; 95% CI, 1.33-1.95) and more frequent in ticagrelor treated patients (56.9%) than in clopidogrel-treated patients (HR, 1.81; 95% CI, 1.55-2.10). An adjusted comparison between prasugrel and ticagrelor-treated groups did not reveal differences in any outcome measure. After adjustment, the death rate was more reduced by novel agents in comparison with clopidogrel (2.9% vs. 6.2%). Conclusions In ACS/PCI patients, prasugrel offered better anti ischemic protection than clopidogrel, whereas use of both novel agents is accompanied by more frequent bleeding events. PMID- 26990960 TI - A New Look at the Factor Structure of the MHC-SF in Iran and the United States Using Exploratory Structural Equation Modeling. AB - OBJECTIVE: This study examined the factor structure and measurement invariance of the Mental Health Continuum-Short Form (MHC-SF) in young adults from Iran and the USA and across gender. METHOD: The sample consisted of 387 Iranian and 395 American university students. Confirmatory factor analysis (CFA) and the new method of exploratory structural equation modeling (ESEM) were used to analyze the data. RESULTS: The three-dimensional model of well-being as measured by the MHC-SF was consistent with the data. ESEM resulted in better fit indices as well as considerably lower factor correlations than did CFA. Partial measurement invariance across nations and full measurement invariance across gender were established. CONCLUSION: The results confirm the three-dimensional structure of mental well-being, and indicate that the items of the MHC-SF function largely similarly across the two nations. These results also showcase the unique value of ESEM in understanding the factor structure of mental well-being. PMID- 26990961 TI - Acidic Properties and Structure-Activity Correlations of Solid Acid Catalysts Revealed by Solid-State NMR Spectroscopy. AB - Solid acid materials with tunable structural and acidic properties are promising heterogeneous catalysts for manipulating and/or emulating the activity and selectivity of industrially important catalytic reactions. On the other hand, the performances of acid-catalyzed reactions are mostly dictated by the acidic features, namely, type (Bronsted vs Lewis acidity), amount, strength, and local environment of acid sites. The latter is relevant to their location (intra- vs extracrystalline), and possible confinement and Bronsted-Lewis acid synergy effects that may strongly affect the host-guest interactions, reaction mechanism, and shape selectivity of the catalytic system. This account aims to highlight some important applications of state-of-the-art solid-state NMR (SSNMR) techniques for exploring the structural and acidic properties of solid acid catalysts as well as their catalytic performances and relevant reaction pathway invoked. In addition, density functional theory (DFT) calculations may be exploited in conjunction with experimental SSNMR studies to verify the structure activity correlations of the catalytic system at a microscopic scale. We describe in this Account the developments and applications of advanced ex situ and/or in situ SSNMR techniques, such as two-dimensional (2D) double-quantum magic-angle spinning (DQ MAS) homonuclear correlation spectroscopy for structural investigation of solid acids as well as study of their acidic properties. Moreover, the energies and electronic structures of the catalysts and detailed catalytic reaction processes, including the identification of reaction species, elucidation of reaction mechanism, and verification of structure-activity correlations, made available by DFT theoretical calculations were also discussed. Relevant discussions will focus primarily on results obtained from our laboratories in the past decade, including (i) quantitative and qualitative acidity characterization utilizing assorted probe molecules, (ii) probing the spatial proximity and synergy effect of acid sites, and (iii) influence of acid features and pore confinement effect on catalytic activity, transition-state stability, reaction pathway, and product selectivity of solid acid catalysts such as zeolites, metal oxides, and heteropolyacids. It is conclusive that a synergy of acidity (local effect) and pore confinement (environmental effect) tend to strongly dictate the formations of intermediates and transition states, hence, the reaction pathways and catalytic performance of solid acid catalysts. We hope that these information can provide additional insights toward our understanding in heterogeneous catalysis, especially the roles of structural and acidic properties on catalytic performances and reaction mechanism of acid-catalyzed systems, which should be beneficial for rational design of solid acid catalysts. PMID- 26990963 TI - Correlation Between Fractional Exhaled Nitric Oxide Levels and Efficacy of Inhaled Corticosteroids in Children With Bronchial Asthma. AB - To investigate correlation between fractional exhaled nitric oxide (FeNO) levels and efficacy of inhaled corticosteroids in children with bronchial asthma. Between October 2013 and December 2014, 133 cases of children with bronchial asthma were randomly divided into the glucocorticoid group (n = 67; inhaled with Seretide/Pulmicort) and the nonglucocorticoid group (n = 66; inhaled with short acting beta2 receptor agonist if needed); and alternatively 72 cases of healthy children were regarded as the control group. FeNO, forced expiratory volume in 1 second to predicted value, forced expiratory volume in 1 second/forced vital capacity, induced sputum eosinophils (EOS)%, and total serum immunoglobulin (Ig) E and serum EOS% were detected and childhood asthma control test (C-ACT) scale was investigated pretreatment and 3 and 6 months posttreatment, respectively. FeNO levels, induced sputum EOS%, total serum IgE, and serum EOS% were significantly lower, whereas forced expiratory volume in 1 second to predicted value, forced expiratory volume in 1 second/forced vital capacity, and C-ACT scores were obviously improved in the glucocorticoid group 6 months posttreatment compared with those of pretreatment (all P < 0.05). FeNO levels, induced sputum EOS%, and total serum IgE were significantly lower, whereas C-ACT scores were significantly higher in the glucocorticoid group compared with those of the nonglucocorticoid group (all P < 0.05). In the glucocorticoid group, induced sputum EOS% and total serum IgE showed significantly positive correlations with FeNO levels (r = 0.73, P < 0.01; r = 0.56, P < 0.01), whereas C-ACT scores were negatively correlated with FeNO levels (r = -0.67, P < 0.01). FeNO levels might be correlated with efficacy of inhaled corticosteroids in children with bronchial asthma. PMID- 26990962 TI - An integrated model for guiding the selection of treatment components for problem behavior maintained by automatic reinforcement. AB - We evaluated the usefulness of 2 assessments to guide treatment selection for individuals whose prior functional analysis indicated that automatic reinforcement maintained their problem behavior. In the 1st assessment, we compared levels of problem behavior during a noncontingent play condition and an alone or ignore condition. In the 2nd, we assessed participants' relative preferences for automatic reinforcement and social reinforcers in a concurrent operants arrangement. We used the results of these 2 assessments to assign 5 participants to a treatment based on noncontingent access to social reinforcers or to a treatment based on differential access to social reinforcers. We conducted monthly probes with the participants over 10 to 12 months to evaluate the effects of the treatment procedures. All participants showed reductions in problem behavior over this period. PMID- 26990964 TI - Is there a link between Holt-Oram Syndrome and 'Mardini-Nyhan' association? - need for further research. PMID- 26990965 TI - Highly Efficient Perovskite Nanocrystal Light-Emitting Diodes Enabled by a Universal Crosslinking Method. AB - The preparation of highly efficient perovskite nanocrystal light-emitting diodes is shown. A new trimethylaluminum vapor-based crosslinking method to render the nanocrystal films insoluble is applied. The resulting near-complete nanocrystal film coverage, coupled with the natural confinement of injected charges within the perovskite crystals, facilitates electron-hole capture and give rise to a remarkable electroluminescence yield of 5.7%. PMID- 26990966 TI - Environmental and socioeconomic factors contributing to elevated blood lead levels in children from an industrial area of Upper Silesia. AB - The present study concentrated on a cross-sectional analysis of recent exposure to lead (Pb) and the socioeconomic factors behind increased Pb exposure in Polish children. Lead is one of the most widespread toxic heavy metals in the industrial region of Upper Silesia (Poland). Elevated blood Pb levels in children continue to be a matter of serious concern. The present study involved 4882 children from the Upper Silesia region, aged from 3 yr to 18 yr, over the calendar years 1999 to 2013. The concentration of Pb in blood was determined in each child. The children's parents were asked to answer survey questions about the child's environmental exposure to Pb as well as the socioeconomic condition of the family. Factors that correspond with increased exposure to Pb included: lower level of education of parents, unemployment, parents' occupational Pb exposure, poor socioeconomic status of the family, smoking at home, living on the ground floor of buildings, consumption of locally grown vegetables and fruits, longer outdoor playing periods in a polluted environment, and male gender. Environmental exposure to Pb is the most important factor behind chronic poisoning of children in Upper Silesia. The most important socioeconomic factor associated with concentrations of Pb in children's blood is a lower level of education of a child's mother and father. Environ Toxicol Chem 2016;35:2597-2603. (c) 2016 SETAC. PMID- 26990968 TI - The intravesicular cocktail and its role in the regulation of exocytosis. AB - The accumulation of neurotransmitters within secretory vesicles (SVs) far exceeds the theoretical tonic concentrations in the cytosol, a phenomenon that has captivated the attention of scientists for decades. For instance, chromaffin granules can accumulate close to molar concentrations of catecholamines, along with many other products like ATP, calcium, peptides, chromogranins, ascorbate, and other nucleotides. In this short review, we will summarize the interactions that are currently believed to occur between the elements that make up the vesicular cocktail in the acidic environment of SVs, and how they permit the accumulation of such high concentrations of certain components. In addition, we will examine how the vesicular cocktail regulates the exocytosis of neurotransmitters. In this review, we have highlighted the mechanisms that permit the storage of neurotransmitters and hormones inside secretory vesicles. We also have proposed a novel model based in the intravesicular interactions of the main components of this inner cocktail - catecholamines, ATP, and chromogranins - to allow the accumulation of near molar concentrations of transmitters in secretory vesicles. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015). PMID- 26990969 TI - Economic evaluation of a computed tomography directed referral strategy for chronic rhinosinusitis. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent chronic inflammatory disease. The basis of a clinical diagnosis of CRS for primary care physicians (PCPs) is based upon the recognition of a symptom constellation that manifests with the disease. However, because the symptomatology of CRS may overlap with other diagnoses, the referral of patient to the most appropriate specialist may not always occur, leading to further delays in evaluation and treatment. METHODS: Given the emphasis on improving the value of health care in Canada, a decision tree model was designed to evaluate whether an upfront computed tomography (CT) scan of the paranasal sinuses ordered by the PCP for a suspected case of CRS would be more cost-effective when compared to symptom-based specialist referral practice. RESULTS: The CT-based strategy resulted in the patient arriving at the most appropriate specialist 95% (+/-5%) of the time while the symptom-based referral strategy resulted in the patient arriving at the correct specialist 77% (+/-18%) of the time. The incremental cost effectiveness ratio (ICER) for the CT based strategy was $1522 per patient arriving at the correct specialist. CONCLUSION: These results suggest that PCPs can improve the effectiveness of their referrals for CRS by utilising an upfront CT referral strategy. However, it would create an additional cost of approximately $1500 per patient referred. Given these findings, the potential clinical benefits of using an upfront CT scan in the Canadian primary care setting should be further studied to determine the value of the additional money spent to improve the effectiveness of CRS referral. PMID- 26990967 TI - Multiscale Metabolic Modeling of C4 Plants: Connecting Nonlinear Genome-Scale Models to Leaf-Scale Metabolism in Developing Maize Leaves. AB - C4 plants, such as maize, concentrate carbon dioxide in a specialized compartment surrounding the veins of their leaves to improve the efficiency of carbon dioxide assimilation. Nonlinear relationships between carbon dioxide and oxygen levels and reaction rates are key to their physiology but cannot be handled with standard techniques of constraint-based metabolic modeling. We demonstrate that incorporating these relationships as constraints on reaction rates and solving the resulting nonlinear optimization problem yields realistic predictions of the response of C4 systems to environmental and biochemical perturbations. Using a new genome-scale reconstruction of maize metabolism, we build an 18000-reaction, nonlinearly constrained model describing mesophyll and bundle sheath cells in 15 segments of the developing maize leaf, interacting via metabolite exchange, and use RNA-seq and enzyme activity measurements to predict spatial variation in metabolic state by a novel method that optimizes correlation between fluxes and expression data. Though such correlations are known to be weak in general, we suggest that developmental gradients may be particularly suited to the inference of metabolic fluxes from expression data, and we demonstrate that our method predicts fluxes that achieve high correlation with the data, successfully capture the experimentally observed base-to-tip transition between carbon-importing tissue and carbon-exporting tissue, and include a nonzero growth rate, in contrast to prior results from similar methods in other systems. PMID- 26990970 TI - Loss of Nigral Hyperintensity on 3 Tesla MRI of Parkinsonism: Comparison With (123) I-FP-CIT SPECT. AB - BACKGROUND: The aim of this study was to investigate whether 3 Tesla susceptibility-weighted imaging can detect the alteration of substantia nigra hyperintensity in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) and to assess the concordance between the loss of nigral hyperintensity on 3 Tesla susceptibility-weighted imaging and the nigrostriatal dopaminergic degeneration indicated by (123) I-2beta-carbomethoxy 3beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computerized tomography. METHODS: Consecutive subjects with suspected parkinsonism were included, and clinical diagnosis was solidified during clinical follow-up. Two blinded neuroradiologists interpreted the nigral hyperintensity on susceptibility-weighted imaging. The performance of susceptibility-weighted imaging for detection of nigral hyperintensity loss was estimated on the basis of the clinical diagnosis and compared with single photon emission computerized tomography results. RESULTS: The study included 210 subjects (126 PD, 11 MSA, 11 PSP patients, 26 healthy controls, 36 disease controls). The presence or absence of nigral hyperintensity was accurately visualized in 112 PD, 7 MSA, and 11 PSP patients and 53 controls. We identified 16 false-negative cases and 11 false positive cases. The sensitivity and specificity of susceptibility-weighted imaging were 88.8% and 83.6%, respectively. The concordance rate between susceptibility-weighted imaging and single photon emission computerized tomography was 86.2%. CONCLUSIONS: The loss of nigral hyperintensity on susceptibility-weighted imaging suggested nigrostriatal dopaminergic degeneration in a large portion of patients with parkinsonism, which was indicated by (123) I 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computerized tomography. In consideration of false-negative and positive cases, well-designed imaging protocols should be introduced to improve the performance of nigral hyperintensity imaging. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26990971 TI - Methods for testing the Markov condition in the illness-death model: a comparative study. AB - Markov three-state progressive and illness-death models are often used in biomedicine for describing survival data when an intermediate event of interest may be observed during the follow-up. However, the usual estimators for Markov models (e.g., Aalen-Johansen transition probabilities) may be systematically biased in non-Markovian situations. On the other hand, despite non-Markovian estimators for transition probabilities and related curves are available, including the Markov information in the construction of the estimators allows for variance reduction. Therefore, testing for the Markov condition is a relevant issue in practice. In this paper, we discuss several characterizations of the Markov condition, with special focus on its equivalence with the quasi independence between left truncation and survival times in standard survival analysis. New methods for testing the Markovianity of an illness-death model are proposed and compared with existing ones by means of an intensive simulation study. We illustrate our findings through the analysis of a data set from stem cell transplant in leukemia. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990972 TI - The detection of flunitrazepam in beverages using portable Raman spectroscopy. AB - Portable Raman spectroscopy has been used for the detection of the date-rape drug flunitrazepam in spiked beverages that may be involved in cases of drug facilitated sexual assault. Solutions of flunitrazepam with different concentrations were prepared in water and for each beverage type. Although some bands attributable to the beverage matrix are present, they did not interfere with the identification of the drug. Definitive evidence for contamination of the spiked drink concerned can be acquired within 10 s. The data can be acquired in situ and sample extraction and/or preparation steps are unnecessary. The ability of portable Raman spectrometers to interrogate spiked alcoholic beverages with flunitrazepam has been demonstrated. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26990973 TI - Characterization of dengue virus infections in a sample of patients suggests unique clinical, immunological, and virological profiles that impact on the diagnosis of dengue and dengue hemorrhagic fever. AB - Dengue virus (DENV) infections are increasing with respect to incidence and severity in the Central Province of Sri Lanka. The objective of this study was to define the clinical, immunological, and virological profiles of patients admitted to the General Hospital, Kandy with clinically apparent dengue. Demographic, clinical, hematological parameters, liver enzymes (ALT and AST), and blood samples were collected from 292 patients with fever <5 days post onset and fulfilling the WHO criteria for the diagnosis of dengue fever/dengue hemorrhagic fever (DF/DHF). Samples were analyzed for, anti-DENV IgM, IgG, and DENV nucleic acid. Myalgia was the commonest complaint by 65% of the patients. Packed cell volume was >45% in 27% of the patients while 42.12% had reduced platelets and 62.67% had reduced white blood cell counts. In contrast to other studies, positive tourniquet test (PTT) and petechiae were not major indicators of DENV infection or severity of the disease. Clinical profiles were significantly different between DF and DHF/DSS and showed many similarities to that reported elsewhere. Altogether, 43 patients (14.73%) were viremic as detected by RT-PCR; 181 patients (62%) were positive for anti-DENV IgM, and 245 (84%) patients were positive for anti-DENV IgG. In combination, anti-DENV IgM and RT-PCR assays detected 224 (77.5%) of DENV infected cases, thus improving the DENV diagnosis rate. Hence, the diagnostic utility of PTT, anti-DENV IgM/IgG serology, or RT-PCR used alone in the early phase of illness is low in Sri Lanka but the diagnostic value can be improved by a combination of serology and RT-PCR. J. Med. Virol. 88:1703-1710, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990974 TI - PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice. AB - BACKGROUND: Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM). However, immune rejection, especially that induced by the alloreactive T cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1) is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time. METHODS: Glucose Stimulation Assays were performed to evaluate whether PD L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT) mice (C57BL/6j) were implanted beneath the renal capsule of streptozotocin (STZ)-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients. RESULTS: PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity. CONCLUSIONS: This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses. PMID- 26990975 TI - Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival. AB - Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases. Furthermore, both SUZ12 and EED mutations in MPNSTs were associated with loss of H3K27 tri-methylation, a downstream target of PRC2. Therefore, we tested whether H3K27me3 immunohistochemistry is useful as a diagnostic and prognostic marker for MPNSTs. We performed H3K27me3 immunohistochemistry in 162 primary MPNSTs, 97 neurofibromas and 341 other tumors using tissue microarray. We observed loss of H3K27me3 in 34% (55/162) of all MPNSTs while expression was retained in all neurofibromas including atypical (n=8) and plexiform subtypes (n=24). Within other tumors we detected loss of H3K27me3 in only 7% (24/341). Surprisingly, 60% (9/15) of synovial sarcomas and 38% (3/8) of fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) showed loss of H3K27 trimethylation. Only 1 out of 44 schwannomas showed loss of H3K27me3 and all 4 perineuriomas showed intact H3K27me3. Furthermore, MPNSTs with loss of H3K27 tri-methylation showed inferior survival compared with MPNSTs with intact H3K27 tri-methylation, which was validated in two independent cohorts. Our results indicate that H3K27me3 immunohistochemistry is useful as a diagnostic marker, in which loss of H3K27me3 favors MPNST above neurofibroma. However, H3K27me3 immunohistochemistry is not suitable to distinguish MPNST from its morphological mimicker synovial sarcoma or fibrosarcomatous DFSP. Since loss of H3K27 tri-methylation was related to poorer survival in MPNST, chromatin modification mediated by this specific histone seems to orchestrate more aggressive tumour biology. PMID- 26990976 TI - Pan-cancer transcriptome analysis reveals a gene expression signature for the identification of tumor tissue origin. AB - Carcinoma of unknown primary, wherein metastatic disease is present without an identifiable primary site, accounts for ~3-5% of all cancer diagnoses. Despite the development of multiple diagnostic workups, the success rate of primary site identification remains low. Determining the origin of tumor tissue is, thus, an important clinical application of molecular diagnostics. Previous studies have paved the way for gene expression-based tumor type classification. In this study, we have established a comprehensive database integrating microarray- and sequencing-based gene expression profiles of 16 674 tumor samples covering 22 common human tumor types. From this pan-cancer transcriptome database, we identified a 154-gene expression signature that discriminated the origin of tumor tissue with an overall leave-one-out cross-validation accuracy of 96.5%. The 154 gene expression signature was first validated on an independent test set consisting of 9626 primary tumors, of which 97.1% of cases were correctly classified. Furthermore, we tested the signature on a spectrum of diagnostically challenging tumors. An overall accuracy of 92% was achieved on the 1248 tumor specimens that were poorly differentiated, undifferentiated or from metastatic tumors. Thus, we have identified a 154-gene expression signature that can accurately classify a broad spectrum of tumor types. This gene panel may hold a promise to be a useful additional tool for the determination of the tumor origin. PMID- 26990977 TI - Mini-zone cyanoacrylate skin surface stripping: a new method for non-invasive sampling of scalp material. PMID- 26990979 TI - Can Hypertrophy of the Contralateral Testis Predict the Absence of a Viable Testis in Infancy with Cryptorchidism: A Prospective Analysis. AB - This prospective study aimed to evaluate whether Contralateral compensatory testicular hypertrophy (CTH) is valid as a predictive tool for a non-viable testis in children aged between 6 and 18 months, and whether CTH is affected by mini-puberty. Seventy-two testes from 60 boys aged between 6 and 18 months were categorized into three groups: 24 testes contralateral to surgically removed non viable testes (NVTs), 24 testes contralateral to surgically corrected undescended testes (UDTs), and 24 testes from a normal controls. Contralateral testicular length and volume were measured with ultrasonography and compared among the groups. Group 1 (NVT) had a significantly longer length and larger volume than group 2 (UDT). The length and volume of each group among three developmental periods (6-10, 10-14, and 14-18 months) were also analyzed. In the controls, the length was significantly larger at 6-10 months than at 10-14 months in accordance with previously reported changes in testicular size due to the effect of "mini puberty." The volume of controls showed a similar pattern, though without statistical significance. However, this pattern was not observed in the NVT and UDT groups. A receiver operating curve revealed that a testicular length of 16.1 mm or a volume of 0.59 ml had the highest sensitivity and specificity for predicting NVTs. The CTH was also found to be valid as a predictive tool for a NVT in children of ages 6 to 18 months, as the effect of mini-puberty appeared to be absent in the NVT and UDT groups. However, the cut-off values were less than those of previous reports. The proper cut-off level according to the age and measurement method should be applied in this developmental period. PMID- 26990980 TI - Effect of multiple-sweeping on ablation performance during ex vivo laser nephrectomy. AB - BACKGROUND AND OBJECTIVE: Fiber-assisted laser surgery has been employed as a minimally invasive method in various medical fields. In spite of multiple sweeping on tissue during laser treatments, the rate of tissue removal gradually decreases and eventually leads to longer irradiation times as well as deeper thermal injury. The objective of the current study was to quantitatively investigate the effect of multiple fiber sweeps on ablation performance during ex vivo 532-nm laser nephrectomy. MATERIALS AND METHODS: Porcine kidney tissue was used to evaluate variations in tissue ablation and coagulative necrosis after pre and multiple-sweeping with a 532 nm wavelength at various fiber speeds (2, 4, and 6 mm/second). The distance between a fiber tip and tissue surface was initially set at 1.5 mm, and no further distance change was performed. Double integrating spheres in conjunction with an adding-doubling method were employed to measure variations in optical properties of the tested tissue. The extent of ablation and coagulation was quantified to identify the role of multiple-sweeping at various fiber conditions. RESULTS: Optical property measurements showed a 30% decrease in light absorption but a more than threefold increase in light scattering after irreversible thermal denaturation. Pre-sweeping yielded insignificant effects on tissue coagulation due to almost consistent coagulation depths with numbers of pre-sweeps. Ablation depths increased with more numbers of fiber sweeps and slower fiber speeds whereas coagulation depths thickened primarily with the slower speeds. Multiple-sweeping induced saturation in ablation volume with the increasing numbers of multiple-sweeps irrespective of the fiber speed. CONCLUSION: A combination of coagulation barriers, spatial distribution of power, and temporal interplay of optical energy could attribute to continuously lessen the amount of the ablated tissue with the multiple sweeps. Optical power modulation with varying fiber conditions (speed and distance) will be examined to optimize surgical parameters and to sustain the equivalent ablation performance of the first sweep with the multiple sweeping for laser nephrectomy. Lasers Surg. Med. 48:616-623, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26990981 TI - Combining the Sterile Insect Technique with the Incompatible Insect Technique: III-Robust Mating Competitiveness of Irradiated Triple Wolbachia-Infected Aedes albopictus Males under Semi-Field Conditions. AB - Combination of the sterile insect technique with the incompatible insect technique is considered to be a safe approach to control Aedes albopictus populations in the absence of an accurate and scalable sex separation system or genetic sexing strain. Our previous study has shown that the triple Wolbachia infected Ae. albopictus strain (wAlbA, wAlbB and wPip) was suitable for mass rearing and females could be completely sterilized as pupae with a radiation dose of at least 28 Gy. However, whether this radiation dose can influence the mating competitiveness of the triple infected males was still unknown. In this study we aimed to evaluate the effects of irradiation on the male mating competitiveness of the triple infected strain under laboratory and semi-field conditions. The results herein indicate that irradiation with a lower, female-sterilizing dose has no negative impact on the longevity of triple infected males while a reduced lifespan was observed in the wild type males (wAlbA and wAlbB) irradiated with a higher male-sterilizing dose, in small cages. At different sterile: fertile release ratios in small cages, triple-infected males induced 39.8, 81.6 and 87.8% sterility in a wild type female population at 1:1, 5:1 and 10:1 release ratios, respectively, relative to a fertile control population. Similarly, irradiated triple infected males induced 31.3, 70.5 and 89.3% sterility at 1:1, 5:1 and 10:1 release ratios, respectively, again relative to the fertile control. Under semi field conditions at a 5:1 release ratio, relative to wild type males, the mean male mating competitiveness index of 28 Gy irradiated triple-infected males was significantly higher than 35 Gy irradiated wild type males, while triple infected males showed no difference in mean mating competitiveness to either irradiated triple-infected or irradiated wild type males. An unexpected difference was also observed in the relative male mating competitiveness of the triple infected strain after irradiation at 28 Gy dose in small vs large cages, with a higher male mating competitiveness index calculated from results of experiments in the large cages. Based on these results, we consider that the male mating performance of the triple infected strain after irradiation at 28 Gy, a dose required for complete female sterility and the avoidance of population replacement, is approximately equal to that of the wild type males under semi-field conditions. Though field evaluation is required, this suggests that the triple infected strain is suitable for irradiation and release as part of a combined SIT-IIT approach to Ae. albopictus control. PMID- 26990982 TI - One-Pot Synthesis of Polysubstituted Benzenes through a N,N-dimethyl-4 aminopyridine (DMAP)-Catalyzed [4+2] Benzannulation of 1,3 Bis(sulfonyl)butadienes and gamma-Substituted Allenoates. AB - A new strategy for the one-pot synthesis of polysubstituted benzenes through a N,N-dimethyl-4-aminopyridine (DMAP)-catalyzed [4+2] benzannulation from readily prepared 1,3-bis(sulfonyl)butadienes and gamma-substituted allenoates is described. This method provides a facile, metal-free and general route to highly substituted benzenes under mild conditions in moderate-to-good yields with complete regioselectivity. PMID- 26990978 TI - Experimental Neuromyelitis Optica Induces a Type I Interferon Signature in the Spinal Cord. AB - Neuromyelitis optica (NMO) is an acute inflammatory disease of the central nervous system (CNS) which predominantly affects spinal cord and optic nerves. Most patients harbor pathogenic autoantibodies, the so-called NMO-IgGs, which are directed against the water channel aquaporin 4 (AQP4) on astrocytes. When these antibodies gain access to the CNS, they mediate astrocyte destruction by complement-dependent and by antibody-dependent cellular cytotoxicity. In contrast to multiple sclerosis (MS) patients who benefit from therapies involving type I interferons (I-IFN), NMO patients typically do not profit from such treatments. How is I-IFN involved in NMO pathogenesis? To address this question, we made gene expression profiles of spinal cords from Lewis rat models of experimental neuromyelitis optica (ENMO) and experimental autoimmune encephalomyelitis (EAE). We found an upregulation of I-IFN signature genes in EAE spinal cords, and a further upregulation of these genes in ENMO. To learn whether the local I-IFN signature is harmful or beneficial, we induced ENMO by transfer of CNS antigen specific T cells and NMO-IgG, and treated the animals with I-IFN at the very onset of clinical symptoms, when the blood-brain barrier was open. With this treatment regimen, we could amplify possible effects of the I-IFN induced genes on the transmigration of infiltrating cells through the blood brain barrier, and on lesion formation and expansion, but could avoid effects of I-IFN on the differentiation of pathogenic T and B cells in the lymph nodes. We observed that I-IFN treated ENMO rats had spinal cord lesions with fewer T cells, macrophages/activated microglia and activated neutrophils, and less astrocyte damage than their vehicle treated counterparts, suggesting beneficial effects of I-IFN. PMID- 26990983 TI - Central Dogma Goes Digital. AB - In this issue of Molecular Cell, Tay and colleagues (Albayrak et al., 2016) describe a new technique to digitally quantify the numbers of protein and mRNA in the same mammalian cell, providing a new way to look at the central dogma of molecular biology. PMID- 26990984 TI - Rewiring Cas9 to Target New PAM Sequences. AB - Papers by Anders et al. (2016) and Hirano et al. (2016b), published in this issue of Molecular Cell, show that SpCas9 uses an induced fit mechanism to recognize altered protospacer adjacent motif (PAM) sequences. PMID- 26990985 TI - An Acetyldegron Triggers CRBN to Take Down the "Q". AB - In this issue of Molecular Cell, Nguyen et al. (2016) show that p300/CBP-mediated acetylation of glutamine synthetase (GS) triggers recognition by the CRL4(CRBN) E3 ubiquitin ligase, resulting in its ubiquitylation and degradation in response to high glutamine concentrations. PMID- 26990986 TI - Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon. AB - Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4(CRBN) and degradation by the proteasome. Binding of acetylated degron peptides to CRBN depends on an intact thalidomide-binding pocket but is not competitive with IMiDs. These findings reveal a feedback loop involving CRL4(CRBN) that adjusts GS protein levels in response to glutamine and uncover a new function for lysine acetylation. PMID- 26990987 TI - Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate. AB - The death-inducing signaling complex (DISC) initiates death receptor-induced apoptosis. DISC assembly and activation are controlled by c-FLIP isoforms, which function as pro-apoptotic (c-FLIPL only) or anti-apoptotic (c-FLIPL/c-FLIPS) regulators of procaspase-8 activation. Current models assume that c-FLIP directly competes with procaspase-8 for recruitment to FADD. Using a functional reconstituted DISC, structure-guided mutagenesis, and quantitative LC-MS/MS, we show that c-FLIPL/S binding to the DISC is instead a co-operative procaspase-8 dependent process. FADD initially recruits procaspase-8, which in turn recruits and heterodimerizes with c-FLIPL/S via a hierarchical binding mechanism. Procaspase-8 activation is regulated by the ratio of unbound c-FLIPL/S to procaspase-8, which determines composition of the procaspase-8:c-FLIPL/S heterodimer. Thus, procaspase-8:c-FLIPL exhibits localized enzymatic activity and is preferentially an activator, promoting DED-mediated procaspase-8 oligomer assembly, whereas procaspase-8:c-FLIPS lacks activity and potently blocks procaspase-8 activation. This co-operative hierarchical binding model explains the dual role of c-FLIPL and crucially defines how c-FLIP isoforms differentially control cell fate. PMID- 26990988 TI - Two-Stage Synapsis of DNA Ends during Non-homologous End Joining. AB - Repair of DNA double-strand breaks (DSBs) is essential for genomic stability. The most common DSB repair mechanism in human cells, non-homologous end joining (NHEJ), rejoins broken DNA ends by direct ligation. It remains unclear how components of the NHEJ machinery assemble a synaptic complex that bridges DNA ends. Here, we use single-molecule imaging in a vertebrate cell-free extract to show that synapsis of DNA ends occurs in at least two stages that are controlled by different NHEJ factors. DNA ends are initially tethered in a long-range complex whose formation requires the Ku70/80 heterodimer and the DNA-dependent protein kinase catalytic subunit. The ends are then closely aligned, which requires XLF, a non-catalytic function of XRCC4-LIG4, and DNA-PK activity. These results reveal a structural transition in the synaptic complex that governs alignment of DNA ends. Our approach provides a means of studying physiological DNA DSB repair at single-molecule resolution. PMID- 26990990 TI - Codon Usage and 3' UTR Length Determine Maternal mRNA Stability in Zebrafish. AB - The control of mRNA stability plays a central role in regulating gene expression. In metazoans, the earliest stages of development are driven by maternally supplied mRNAs. The degradation of these maternal mRNAs is critical for promoting the maternal-to-zygotic transition of developmental programs, although the underlying mechanisms are poorly understood in vertebrates. Here, we characterized maternal mRNA degradation pathways in zebrafish using a transcriptome analysis and systematic reporter assays. Our data demonstrate that ORFs enriched with uncommon codons promote deadenylation by the CCR4-NOT complex in a translation-dependent manner. This codon-mediated mRNA decay is conditional on the context of the 3' UTR, with long 3' UTRs conferring resistance to deadenylation. These results indicate that the combined effect of codon usage and 3' UTR length determines the stability of maternal mRNAs in zebrafish embryos. Our study thus highlights the codon-mediated mRNA decay as a conserved regulatory mechanism in eukaryotes. PMID- 26990989 TI - SON and Its Alternatively Spliced Isoforms Control MLL Complex-Mediated H3K4me3 and Transcription of Leukemia-Associated Genes. AB - Dysregulation of MLL complex-mediated histone methylation plays a pivotal role in gene expression associated with diseases, but little is known about cellular factors modulating MLL complex activity. Here, we report that SON, previously known as an RNA splicing factor, controls MLL complex-mediated transcriptional initiation. SON binds to DNA near transcription start sites, interacts with menin, and inhibits MLL complex assembly, resulting in decreased H3K4me3 and transcriptional repression. Importantly, alternatively spliced short isoforms of SON are markedly upregulated in acute myeloid leukemia. The short isoforms compete with full-length SON for chromatin occupancy but lack the menin-binding ability, thereby antagonizing full-length SON function in transcriptional repression while not impairing full-length SON-mediated RNA splicing. Furthermore, overexpression of a short isoform of SON enhances replating potential of hematopoietic progenitors. Our findings define SON as a fine-tuner of the MLL-menin interaction and reveal short SON overexpression as a marker indicating aberrant transcriptional initiation in leukemia. PMID- 26990991 TI - Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas9. AB - The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets bearing a PAM (protospacer adjacent motif) and complementarity to the guide RNA. A recent study showed that, whereas wild-type Streptococcus pyogenes Cas9 (SpCas9) recognizes the 5'-NGG-3' PAM, the engineered VQR, EQR, and VRER SpCas9 variants recognize the 5'-NGA-3', 5'-NGAG-3', and 5'-NGCG-3' PAMs, respectively, thus expanding the targetable sequences in Cas9-mediated genome editing applications. Here, we present the high-resolution crystal structures of the three SpCas9 variants in complexes with a single-guide RNA and its altered PAM-containing, partially double-stranded DNA targets. A structural comparison of the three SpCas9 variants with wild-type SpCas9 revealed that the multiple mutations synergistically induce an unexpected displacement in the phosphodiester backbone of the PAM duplex, thereby allowing the SpCas9 variants to directly recognize the altered PAM nucleotides. Our findings explain the altered PAM specificities of the SpCas9 variants and establish a framework for further rational engineering of CRISPR-Cas9. PMID- 26990992 TI - Structural Plasticity of PAM Recognition by Engineered Variants of the RNA-Guided Endonuclease Cas9. AB - The RNA-guided endonuclease Cas9 from Streptococcus pyogenes (SpCas9) forms the core of a powerful genome editing technology. DNA cleavage by SpCas9 is dependent on the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) in the target DNA, restricting the choice of targetable sequences. To address this limitation, artificial SpCas9 variants with altered PAM specificities have recently been developed. Here we report crystal structures of the VQR, EQR, and VRER SpCas9 variants bound to target DNAs containing their preferred PAM sequences. The structures reveal that the non-canonical PAMs are recognized by an induced fit mechanism. Besides mediating sequence-specific base recognition, the amino acid substitutions introduced in the SpCas9 variants facilitate conformational remodeling of the PAM region of the bound DNA. Guided by the structural data, we engineered a SpCas9 variant that specifically recognizes NAAG PAMs. Taken together, these studies inform further development of Cas9-based genome editing tools. PMID- 26990994 TI - Digital Quantification of Proteins and mRNA in Single Mammalian Cells. AB - Absolute quantification of macromolecules in single cells is critical for understanding and modeling biological systems that feature cellular heterogeneity. Here we show extremely sensitive and absolute quantification of both proteins and mRNA in single mammalian cells by a very practical workflow that combines proximity ligation assay (PLA) and digital PCR. This digital PLA method has femtomolar sensitivity, which enables the quantification of very small protein concentration changes over its entire 3-log dynamic range, a quality necessary for accounting for single-cell heterogeneity. We counted both endogenous (CD147) and exogenously expressed (GFP-p65) proteins from hundreds of single cells and determined the correlation between CD147 mRNA and the protein it encodes. Using our data, a stochastic two-state model of the central dogma was constructed and verified using joint mRNA/protein distributions, allowing us to estimate transcription burst sizes and extrinsic noise strength and calculate the transcription and translation rate constants in single mammalian cells. PMID- 26990993 TI - Resources for the Comprehensive Discovery of Functional RNA Elements. AB - Transcriptome-wide maps of RNA binding protein (RBP)-RNA interactions by immunoprecipitation (IP)-based methods such as RNA IP (RIP) and crosslinking and IP (CLIP) are key starting points for evaluating the molecular roles of the thousands of human RBPs. A significant bottleneck to the application of these methods in diverse cell lines, tissues, and developmental stages is the availability of validated IP-quality antibodies. Using IP followed by immunoblot assays, we have developed a validated repository of 438 commercially available antibodies that interrogate 365 unique RBPs. In parallel, 362 short-hairpin RNA (shRNA) constructs against 276 unique RBPs were also used to confirm specificity of these antibodies. These antibodies can characterize subcellular RBP localization. With the burgeoning interest in the roles of RBPs in cancer, neurobiology, and development, these resources are invaluable to the broad scientific community. Detailed information about these resources is publicly available at the ENCODE portal (https://www.encodeproject.org/). PMID- 26990995 TI - Association of Improvement in Pain With Therapeutic Response as Determined by Individual Improvement Criteria in Patients With Rheumatoid Arthritis. AB - OBJECTIVE: To use statistical methods to establish a threshold for individual response in patient-reported outcomes (PROs) in patients with rheumatoid arthritis. METHODS: We used an analysis of variance model in patients on stable therapy (discovery cohort) to establish critical differences (dcrit ) for the minimum change associated with a significant individual patient response (beyond normal variation) in the PRO measures of pain (0-10), fatigue (0-10), and function (Funktionsfragebogen Hannover questionnaire; 0-100). We then evaluated PRO responses in patients initiating adalimumab in a noninterventional study (treatment cohort). RESULTS: In the discovery cohort (n = 700), PROs showed excellent long-term retest reliability. The minimum change that exceeded random fluctuation was conservatively determined to be 3 points for pain, 4 points for fatigue, and 16 points for function. In the treatment cohort (n = 2,788), 1,483 patients (53.2%) achieved a significant individual therapeutic response as assessed by Disease Activity Score in 28 joints (DAS28)-dcrit (>=1.8 points) after 12 months of adalimumab treatment; 68.5% of patients with a DAS28-dcrit response achieved a significant improvement in pain, whereas approximately 40% achieved significant improvements in fatigue or function. Significant improvements in all 3 PROs occurred in 22.7% of patients; 22.8% did not have any significant PRO responses. In contrast, significant improvements in all 3 PROs occurred in only 4.4% of 1,305 patients who did not achieve a DAS28-dcrit response at month 12, and 59.1% did not achieve any significant PRO responses. CONCLUSION: The establishment of critical differences in PROs distinguishes true responses from random variation and provides insights into appropriate patient management. PMID- 26990996 TI - Generation and Characterization of a Tissue-Specific Centrosome Indicator Mouse Line. AB - Centrosomes are major microtubule organizing centers (MTOCs) that play an important role in chromosome segregation during cell division. Centrosomes provide a stable anchor for microtubules, constituting the centers of the spindle poles in mitotic cells, and determining the orientation of cell division. However, visualization of centrosomes is challenging because of their small size. Especially in mouse tissues, it has been extremely challenging to observe centrosomes belonging to a specific cell type of interest among multiple comingled cell types. To overcome this obstacle, we generated a tissue-specific centrosome indicator. In this mouse line, a construct containing a floxed neomyocin resistance gene with a triplicate polyA sequence followed by an EGFP Centrin1 fusion cassette was knocked into the Rosa locus. Upon Cre-mediated excision, EGFP-Centrin1 was expressed under the control of the Rosa locus. Experiments utilizing mouse embryo fibroblasts (MEFs) demonstrated the feasibility of real-time imaging, and showed that EGFP-Centrin1 expression mirrored the endogenous centrosome cycle, undergoing precisely one round of duplication through the cell cycle. Moreover, experiments using embryo and adult mouse tissues demonstrated that EGFP-Centrin1 specifically mirrors the localization of endogenous centrosomes. genesis 54:286-296, 2016. (c) 2016 The Authors. Genesis Published by Wiley Periodicals, Inc. PMID- 26990997 TI - Role of cancer stem cells in racial disparity in colorectal cancer. AB - Although African-Americans (AAs) have a higher incidence of colorectal cancer (CRC) than White people, the underlying biochemical mechanisms for this increase are poorly understood. The current investigation was undertaken to examine whether differences in self-renewing cancer stem/stem-like cells (CSCs) in the colonic mucosa, whose stemness is regulated by certain microRNAs (miRs), could partly be responsible for the racial disparity in CRC. The study contains 53 AAs and 47 White people. We found the number of adenomas and the proportion of CD44(+) CD166(- ) CSC phenotype in the colon to be significantly higher in AAs than White people. MicroRNAs profile in CSC-enriched colonic mucosal cells, expressed as ratio of high-risk (>=3 adenomas) to low-risk (no adenoma) CRC patients revealed an 8-fold increase in miR-1207-5p in AAs, compared to a 1.2 fold increase of the same in White people. This increase in AA was associated with a marked rise in lncRNA PVT1 (plasmacytoma variant translocation 1), a host gene of miR-1207-5p. Forced expression of miR-1207-5p in normal human colonic epithelial cells HCoEpiC and CCD841 produced an increase in stemness, as evidenced by morphologically elongated epithelial mesenchymal transition( EMT) phenotype and significant increases in CSC markers (CD44, CD166, and CD133) as well as TGF-beta, CTNNB1, MMP2, Slug, Snail, and Vimentin, and reduction in Twist and N-Cadherin. Our findings suggest that an increase in CSCs, specifically the CD44(+) CD166(-) phenotype in the colon could be a predisposing factor for the increased incidence of CRC among AAs. MicroRNA 1207-5p appears to play a crucial role in regulating stemness in colonic epithelial cells in AAs. PMID- 26990998 TI - Continuous delivery of naltrexone and nalmefene leads to tolerance in reducing alcohol drinking and to supersensitivity of brain opioid receptors. AB - Opioid antagonist treatments reduce alcohol drinking in rodent models and in alcohol-dependent patients, with variable efficacy across different studies. These treatments may suffer from the development of tolerance and opioid receptor supersensitivity, as suggested by preclinical models showing activation of these processes during and after subchronic high-dose administration of the short acting opioid antagonist naloxone. In the present study, we compared equipotent low and moderate daily doses of naltrexone and nalmefene, two opioid antagonists in the clinical practice for treatment of alcoholism. The antagonists were given here subcutaneously for 7 days either as daily injections or continuous osmotic minipump-driven infusions to alcohol-preferring AA rats having trained to drink 10% alcohol in a limited access protocol. One day after stopping the antagonist treatment, [35 S]GTPgammaS autoradiography on brain cryostat sections was carried out to examine the coupling of receptors to G protein activation. The results prove the efficacy of repeated injections over infused opioid antagonists in reducing alcohol drinking. Tolerance to the reducing effect on alcohol drinking and to the enhancement of G protein coupling to MU-opioid receptors in various brain regions were consistently detected only after infused antagonists. Supersensitivity of kappa-opioid receptors was seen in the ventral and dorsal striatal regions especially by infused nalmefene. Nalmefene showed no clear agonistic activity in rat brain sections or at human recombinant kappa-opioid receptors. The findings support the as-needed dosing practice, rather than the standard continual dosing, in the treatment of alcoholism with opioid receptor antagonists. PMID- 26991000 TI - Luminescent Cages: Pendant Emissive Units on [Pd2L4](4+) "Click" Cages. AB - The photophysics of a family of exo-functionalized [Pd2L4](4+) metallo supramolecular cage architectures constructed from a tripyridyl 1,2,3-triazole backbone are reported. Several spectroscopic techniques are employed including both electronic (steady-state and transient absorption and emission) and vibrational (resonant and nonresonant Raman) methods. These experimental results are interpreted alongside simulated results from density functional theory calculations of the system's vibrational and electronic properties. The ligands and cages are shown to be essentially insulated from the exo-functionalization. They exhibit electronic transitions in the UV region and excited-state properties that are little affected by formation of the cage. Upon functionalization, characteristic Raman bands, electronic transitions, and emission bands associated with, and confined to, the substituent are observed. PMID- 26990999 TI - Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence. AB - Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate. Consistent with the role of DICER1 in the biogenesis of microRNAs, we found differential patterns of microRNA expression in mice treated with metformin or caloric restriction, two proven life extending interventions. Interestingly, several microRNAs previously associated with senescence and aging, including miR-20a, miR-34a, miR-130a, miR-106b, miR 125, and let-7c, were found elevated. In agreement with these findings, treatment with metformin decreased cellular senescence in several senescence models in a DICER1-dependent manner. Metformin lowered p16 and p21 protein levels and the abundance of inflammatory cytokines and oncogenes that are hallmarks of the senescence-associated secretory phenotype (SASP). These data lead us to hypothesize that changes in DICER1 levels may be important for organismal aging and to propose that interventions that upregulate DICER1 expression (e.g., metformin) may offer new pharmacotherapeutic approaches for age-related disease. PMID- 26991002 TI - Correction: Extensive Recombination of a Yeast Diploid Hybrid through Meiotic Reversion. PMID- 26991001 TI - Structural studies of neuropilin-2 reveal a zinc ion binding site remote from the vascular endothelial growth factor binding pocket. AB - Neuropilin-2 is a transmembrane receptor involved in lymphangiogenesis and neuronal development. In adults, neuropilin-2 and its homologous protein neuropilin-1 have been implicated in cancers and infection. Molecular determinants of the ligand selectivity of neuropilins are poorly understood. We have identified and structurally characterized a zinc ion binding site on human neuropilin-2. The neuropilin-2-specific zinc ion binding site is located near the interface between domains b1 and b2 in the ectopic region of the protein, remote from the neuropilin binding site for its physiological ligand, i.e. vascular endothelial growth factor. We also present an X-ray crystal structure of the neuropilin-2 b1 domain in a complex with the C-terminal sub-domain of VEGF-A. Zn(2+) binding to neuropilin-2 destabilizes the protein structure but this effect was counteracted by heparin, suggesting that modifications by glycans and zinc in the extracellular matrix may affect functional neuropilin-2 ligand binding and signalling activity. PMID- 26991004 TI - Potency of Full-Length MGF to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations. AB - AIMS: To compare full-length mechano growth factor (full-length MGF) with human recombinant insulin-like growth factor-I (IGF-I) and human recombinant insulin (HI) in their ability to activate the human IGF-I receptor (IGF-IR), the human insulin receptor (IR-A) and the human insulin receptor-B (IR-B), respectively. In addition, we tested the stimulatory activity of human MGF and its stabilized analog Goldspink-MGF on the IGF-IR. METHODS: The effects of full-length MGF, IGF I, human mechano growth factor (MGF), Goldspink-MGF and HI were compared using kinase specific receptor activation (KIRA) bioassays specific for IGF-I, IR-A or IR-B, respectively. These assays quantify activity by measuring auto phosphorylation of the receptor upon ligand binding. RESULTS: IGF-IR: At high equimolar concentrations maximal IGF-IR stimulating effects generated by full length MGF were similar to that of IGF-I (89-fold vs. 77-fold, respectively). However, EC50 values of IGF-I and full-length MGF for the IGF-I receptor were 0.86 nmol/L (95% CI 0.69-1.07) and 7.83 nmol/L (95% CI: 4.87-12.58), respectively. No IGF-IR activation was observed by human MGF and Goldspink-MGF, respectively. IR-A/IR-B: At high equimolar concentrations similar maximal IR-A stimulating effects were observed for full -length MGF and HI, but maximal IR-B stimulation achieved by full -length MGF was stronger than that by HI (292-fold vs. 98-fold). EC50 values of HI and full-length MGF for the IR-A were 1.13 nmol/L (95% CI 0.69-1.84) and 73.11 nmol/L (42.87-124.69), respectively; for IR-B these values were 1.28 nmol/L (95% CI 0.64-2.57) and 35.10 nmol/L (95% 17.52-70.33), respectively. CONCLUSIONS: Full-length MGF directly stimulates the IGF-IR. Despite a higher EC50 concentration, at high equimolar concentrations full-length MGF showed a similar maximal potency to activate the IGF-IR as compared to IGF-I. Further research is needed to understand the actions of full-length MGF in vivo and to define the physiological relevance of our in vitro findings. PMID- 26991003 TI - Synergistic interaction of glyceraldehydes-3-phosphate dehydrogenase and ArsJ, a novel organoarsenical efflux permease, confers arsenate resistance. AB - Microbial biotransformations are major contributors to the arsenic biogeocycle. In parallel with transformations of inorganic arsenic, organoarsenicals pathways have recently been recognized as important components of global cycling of arsenic. The well-characterized pathway of resistance to arsenate is reduction coupled to arsenite efflux. Here, we describe a new pathway of arsenate resistance involving biosynthesis and extrusion of an unusual pentavalent organoarsenical. A number of arsenic resistance (ars) operons have two genes of unknown function that are linked in these operons. One, gapdh, encodes the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The other, arsJ, encodes a major facilitator superfamily (MFS) protein. The two genes were cloned from the chromosome of Pseudomonas aeruginosa. When expressed together, but not alone, in Escherichia coli, gapdh and arsJ specifically conferred resistance to arsenate and decreased accumulation of As(V). Everted membrane vesicles from cells expressing arsJ accumulated As(V) in the presence of purified GAPDH, D glceraldehylde 3-phosphate (G3P) and NAD(+) . GAPDH forms the unstable organoarsenical 1-arseno-3-phosphoglycerate (1As3PGA). We propose that ArsJ is an efflux permease that extrudes 1As3PGA from cells, where it rapidly dissociates into As(V) and 3-phosphoglycerate (3PGA), creating a novel pathway of arsenate resistance. PMID- 26991005 TI - The characteristics of oncology social work in Australia: Implications for workforce planning in integrated cancer care. AB - AIMS: To describe the demographics, professional characteristics, self-reported professional development needs and research involvement of oncology social workers in Australia and to describe perceived barriers to provision of quality psychosocial care. METHODS: A cross-sectional online survey was administered to social workers working in the oncology field who were contacted through three professional organizations; the Australian Association of Social Workers, Oncology Social Work Australia and the Psycho-oncology Co-operative Research Group, the University of Sydney. A snowball recruitment method was adopted to maximize the sample size. RESULTS: Two thirds of respondents had over 10 years professional practice experience but with lesser experience in oncology settings. Twenty-eight percent had post-graduate qualifications. Professional development needs were reported as moderate or high by 68% of respondents. No association between professional needs and work setting was found. Years of experience in oncology practice and living in an urban area increased the likelihood of involvement in research. Barriers to psychosocial care included poor understandings of the social work role, time constraints and an inadequate number of social work positions. CONCLUSION: In this first Australian study of the social work oncology workforce, the results demonstrated active, well-qualified and experienced social workers providing frontline services to people with cancer and their caregivers in geographically diverse locations across Australia. Inadequate resources and a lack of integrated psychosocial care were identified as barriers to comprehensive cancer care. The need for Aboriginal and Torres Strait Islander social workers was identified as an urgent workforce priority. PMID- 26991006 TI - The definition, diagnostic testing, and management of chronic inducible urticarias - The EAACI/GA(2) LEN/EDF/UNEV consensus recommendations 2016 update and revision. AB - These recommendations for the definition, diagnosis and management of chronic inducible urticaria (CIndU) extend, revise and update our previous consensus report on physical urticarias and cholinergic urticaria (Allergy, 2009). The aim of these recommendations is to improve the diagnosis and management of patients with CIndU. Our recommendations acknowledge the latest changes in our understanding of CIndU, and the available therapeutic options, as well as the development of novel diagnostic tools. PMID- 26991008 TI - Recent advances in prostate cancer pathology: Gleason grading and beyond. AB - Since its initial description in 1966 by Dr Donald Gleason, Gleason grading has become the cornerstone in the management of prostate cancer (PCa). With widespread use of Prostate Specific Antigen (PSA) screening and needle core biopsy, the diagnosis and management of PCa have dramatically evolved. In addition, better understanding of the morphological spectrum of prostate cancer and its clinical significance have prompted the refinement of the grading criteria and reporting guidelines commensurate to contemporary practice. The modification of the Gleason grading system implemented by the International Society of Urological Pathology in 2005 and subsequent revision in 2014 has profoundly impacted how PCa is graded and managed. This review aims to provide a concise update on the refinement of the histological criteria for various Gleason patterns and problem areas of Gleason grading, and provide recommendations on how to improve the grading reproducibility. The new proposal to group Gleason scores into clinically meaningful "grade groups" will also be discussed. Finally, we will discuss how magnetic resonance imaging (MRI)-targeted biopsy and emerging genetic markers may help improve the Gleason grading accuracy and risk stratification currently based on clinicopathological parameters. PMID- 26991007 TI - Aggregation of Trp > Glu point mutants of human gamma-D crystallin provides a model for hereditary or UV-induced cataract. AB - Numerous mutations and covalent modifications of the highly abundant, long-lived crystallins of the eye lens cause their aggregation leading to progressive opacification of the lens, cataract. The nature and biochemical mechanisms of the aggregation process are poorly understood, as neither amyloid nor native-state polymers are commonly found in opaque lenses. The betagamma-crystallin fold contains four highly conserved buried tryptophans, which can be oxidized to more hydrophilic products, such as kynurenine, upon UV-B irradiation. We mimicked this class of oxidative damage using Trp->Glu point mutants of human gammaD crystallin. Such substitutions may represent a model of UV-induced photodamage introduction of a charged group into the hydrophobic core generating "denaturation from within." The effects of Trp->Glu substitutions were highly position dependent. While each was destabilizing, only the two located in the bottom of the double Greek key fold-W42E and W130E-yielded robust aggregation of partially unfolded intermediates at 37 degrees C and pH 7. The alphaB-crystallin chaperone suppressed aggregation of W130E, but not W42E, indicating distinct aggregation pathways from damage in the N-terminal vs C-terminal domain. The W130E aggregates had loosely fibrillar morphology, yet were nonamyloid, noncovalent, showed little surface hydrophobicity, and formed at least 20 degrees C below the melting temperature of the native beta-sheets. These features are most consistent with domain-swapped polymerization. Aggregation of partially destabilized crystallins under physiological conditions, as occurs in this class of point mutants, could provide a simple in vitro model system for drug discovery and optimization. PMID- 26991009 TI - HbH Constant Spring disease has lower serum ferritin relative to liver iron concentration (LIC): importance of LIC measurement and potential impact on serum ferritin thresholds for iron chelation. PMID- 26991010 TI - Effect of total knee arthroplasty on other joints in patients with rheumatoid arthritis evaluated by 18-FDG-PET. AB - AIM: The objective of this study was to assess arthritis of the whole body before and after total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) using positron emission tomography (PET). METHOD: Seventeen knees of 17 RA patients (median age 68 years) who underwent TKA were included in this study. Clinical assessments of disease activity, knee function and activities of daily living (ADL) were performed before and after TKA. 18 Fluorodeoxyglucose (FDG)-PET was performed preoperatively and 12 weeks postoperatively when RA disease activity was assessed. The maximal standardized uptake value (SUV) in the region of interest was used to assess FDG uptake. RESULTS: Disease activity and knee function improved in all patients after TKA. There was a significant decrease in the number of patients with swollen or tender joints involving the right wrist, right knee and left knee. The SUV of bilateral wrist joints decreased significantly 12 weeks after TKA, whereas the SUVs of other large joints were unchanged. CONCLUSION: TKA can improve not only ADL and knee function, but also the disease activity index in RA patients. However, TKA has limited effectiveness against synovitis of the joints not undergoing surgery. PMID- 26991011 TI - Histological and ultrastructural investigation of the female reproductive system of Argulus bengalensis Ramakrishna, 1951 (Crustacea: Branchiura). AB - In order to understand branchiuran reproductive biology, it is imperative to know the sites of oogenesis and oocyte maturation, locate the accessory reproductive glands, and identify the fertilization site with the present knowledge of the sperm transfer mechanism of the genus Argulus. With these objectives, we attempted to describe the female reproductive system of Argulus bengalensis using serial histological sections through the ovaries and associated ducts in the transverse, longitudinal, and sagittal planes. The reproductive organs include a median ovary, one pair of ovarian lumina, a median oviduct, and a pair of collateral accessory glands. A duct from each of the collateral accessory glands leads into the proximal part of the median oviduct, which opens to the exterior through a genital opening at the distal end. The glandular secretion presumably contributes to the jelly coat of the egg. The ovary is bound with a tunica propria which extends further diametrically inside the ovary forming the paired lumina. The lumina are confluent into the median oviduct. Two distinct areas, the germarium and differentiating zones, are clearly distinguishable within the ovary. The tunica propria itself houses the oogonia within a matrix, serving as the germarium. Transmission electron micrograph reveals that the matrix is made of collagen. The collagen matrix confers elasticity to the tunica propria to accommodate the postvitellogenic oocytes within the ovarian lumen. The differentiating zone is situated in between the germarium: dorsally it is covered with a chromatophore layer. The ovary is ensheathed by a circum ovarian striated muscle. The presence of spermatophores in the ovarian lumen indicates the fertilization site. J. Morphol. 277:707-716, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991012 TI - The posteromedial thigh (PMT) flap for lower extremity reconstruction. AB - BACKGROUND: The posteromedial thigh (PMT) perforator flap is a new reliable flap with versatility. The purpose of this article was to report our experience with the use of free PMT flaps for reconstruction of defects of the lower extremity. PATIENTS AND METHODS: From July 2014 to May 2015, 8 patients received reconstruction with 8 free PMT flaps. The defect locations included the heel (1 case), dorsal foot (2 cases), plantar foot (1 case), lateral malleolus (1 case), Achilles tendon (1 case), and tibia (2 cases). Flaps were raised based on the first medial perforator of the profunda femoris artery (PFA) (7 cases) and medial circumflex femoral artery (LCFA) perforator (1 case). The dorsalis pedis artery (3 cases), anterior tibia artery (1 cases), posterior tibial artery (3 cases), and medial sural pedicle (1 case) were dissected as recipient vessels. RESULTS: The flap sizes varied from 10 * 10 to 30 * 11 cm. All the flaps survived completely after surgery. The donor sites were all primarily closed with minimal morbidities. Follow-up observations were conducted for 3-12 months, and all patients had good functional recovery with satisfactory cosmetic results. CONCLUSION: Perforators arising from the PFA in the posterior medial thigh can be used to design pliable fasciocutaneous flaps. The pedicle length and the vessel diameter are adequate for microvascular anastomosis to the lower extremities recipient vessels. The free PMT flap serves as a good new option for reconstructing lower extremity defects. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:865-872, 2017. PMID- 26991013 TI - Why is gynodioecy a rare but widely distributed sexual system? Lessons from the Lamiaceae. AB - Gynodioecy, a sexual system where females and hermaphrodites co-occur, is found in << 1% of angiosperm species. To understand why gynodioecy is rare, we need to understand why females are maintained in some lineages, but not in others. We modelled the evolution of gynodioecy in the Lamiaceae, and investigated whether transition rates between gynodioecious and nongynodioecious states varied across the family. We also investigated whether the evolution of gynodioecy was correlated with the evolution of a herbaceous growth form and temperate distribution. Transition rates differed between Lamiaceae subfamilies. In the Nepetoideae, there were many transitions towards gynodioecy (n = 11), but also many reversions to nongynodioecy (n = 29). In addition, a herbaceous growth form, but not a temperate distribution, affected the rate of transitions both towards and away from gynodioecy; transitions towards gynodioecy occurred ~16 times more frequently and transitions away from gynodioecy occurred ~11 times more frequently in herbaceous lineages than in woody lineages. Within the Lamiaceae, lineages in which gynodioecy has frequently evolved also have a high rate of reversions to the nongynodioecious state. Consequently, to understand why gynodioecy is rare, we need to understand why sexual systems are more evolutionarily labile in some lineages than in others. PMID- 26991014 TI - Soluble Adenylyl Cyclase Regulates Bile Salt-Induced Apoptosis in Human Cholangiocytes. AB - Anion exchanger 2 (AE2), the principal bicarbonate secretor in the human biliary tree, is down-regulated in primary biliary cholangitis. AE2 creates a "bicarbonate umbrella" that protects cholangiocytes from the proapoptotic effects of bile salts by maintaining them deprotonated. We observed that knockdown of AE2 sensitized immortalized H69 human cholangiocytes to not only bile salt-induced apoptosis (BSIA) but also etoposide-induced apoptosis. Because the toxicity of etoposide is pH-independent, there could be a more general mechanism for sensitization of AE2-depleted cholangiocytes to apoptotic stimuli. We found that AE2 deficiency led to intracellular bicarbonate accumulation and increased expression and activity of soluble adenylyl cyclase (sAC), an evolutionarily conserved bicarbonate sensor. Thus, we hypothesized that sAC regulates BSIA. H69 cholangiocytes and primary mouse cholangiocytes were used as models. The sAC specific inhibitor KH7 not only reversed sensitization to BSIA in AE2-depleted H69 cholangiocytes but even completely prevented BSIA. sAC knockdown by tetracycline-inducible short hairpin RNA also prevented BSIA. In addition, sAC inhibition reversed BSIA membrane blebbing, nuclear condensation, and DNA fragmentation. Furthermore, sAC inhibition also prevented BSIA in primary mouse cholangiocytes. Mechanistically, sAC inhibition prevented Bax phosphorylation at Thr167 and mitochondrial translocation of Bax and cytochrome c release but not c Jun N-terminal kinase activation during BSIA. Finally, BSIA in H69 cholangiocytes was inhibited by intracellular Ca(2+) chelation, aggravated by thapsigargin, and unaffected by removal of extracellular calcium. CONCLUSIONS: BSIA is regulated by sAC, depends on intracellular Ca(2+) stores, and is mediated by the intrinsic apoptotic pathway; down-regulation of AE2 in primary biliary cholangitis sensitizes cholangiocytes to apoptotic insults by activating sAC, which may play a crucial role in disease pathogenesis. (Hepatology 2016;64:522-534). PMID- 26991015 TI - High incorporation of long-chain fatty acids contributes to the efficient production of acylated ghrelin in ghrelin-producing cells. AB - The mechanisms for supplying octanoic acid for ghrelin acylation in X/A-like cells are incompletely understood. We found that long-chain fatty acids were incorporated at a higher rate in the ghrelin-producing cell line MGN3-1 than in MIN6 cells, in part due to higher expression level of long-chain fatty acyl-CoA synthetase family member 1 (Acsl1). Inhibition of ACSLs by triacsin C profoundly suppressed acylated ghrelin production. These results suggest that high incorporation of long-chain fatty acids into the ghrelin-producing cells plays a role in the supply of octanoic acid for ghrelin acylation. PMID- 26991016 TI - The Differential Impact of Tourette's Syndrome and Comorbid Diagnosis on the Quality of Life and Functioning of Diagnosed Children and Adolescents. AB - PROBLEM: Tourette's syndrome (TS) is a neuropsychiatric disorder associated with adverse outcomes. High rates of comorbidity (80-90%) complicate presentation, yet the relationship among TS, common comorbid diagnoses, and adversity is not well understood. This research investigated the impact of comorbidity, and the discrete effects of common comorbid diagnoses, on quality of life (QoL) and functioning of youth with TS. METHODS: A community sample of parents of youth with TS (n = 86) participated in this survey-based study. Differences in QoL (Pediatric Quality of Life Inventory) and rates of psychological, behavioral, and social difficulties (Strength and Difficulties Questionnaire) reported for youth with or without comorbid disorder were determined, in addition to outcomes associated with individual disorders. FINDINGS: Parametric and nonparametric analyses revealed strong associations between comorbidity and decreased global QoL, impaired emotional and school functioning, and increased emotional symptomatology (p < .001). The impact of individual comorbid disorders was restricted and disorder specific, and TS was uniquely associated with impaired social functioning and peer relationship problems. CONCLUSIONS: Understanding the risks associated with TS, particularly to psychosocial well-being, and the specific risks accompanying individual comorbid disorders, may improve assessment, prioritization of treatment goals, and interventions targeting the individual, multidimensional needs of youth with TS. PMID- 26991017 TI - Hemoculture and Direct Sputum Detection of mecA-Mediated Methicillin-Resistant Staphylococcus aureus by Loop-Mediated Isothermal Amplification in Combination With a Lateral-Flow Dipstick. AB - This study reports loop-mediated isothermal amplification (LAMP) for rapid detection of methicillin-resistant Staphylococcus aureus from direct clinical specimens. Four primers including outer and inner primers were specifically designed on the two target sequences-femB to identify S. aureus and mecA to identify antibiotic-resistant gene. Reference strains including various species of gram-positive/gram-negative isolates were used to evaluate and optimize LAMP assays. The optimum LAMP condition was found at 63 degrees C within 70 min assay time (include hybridization with FITC probe for 5 min and further 5 min for reading the results on the lateral flow dipstick). The detection limits of LAMP for mecA was 10 pg of total DNA or 100 CFU/ml. The LAMP assays were applied to a total of 155 samples of direct DNA extraction from sputum and hemoculture bottles. The sensitivity of LAMP for mecA detection in sputum and hemoculture bottles was 93.3% (28/30) and 100% (52/52), respectively. In conclusion, LAMP assay is an alternative technique for rapid detection of MRSA infection with a technical simplicity and cost-effective method in a routine diagnostic laboratory. PMID- 26991018 TI - The ventromedial hypothalamus mediates predator fear memory. AB - The amygdala has been shown to be essential for the processing of acute and learned fear across animal species. However, the downstream neural circuits that mediate these fear responses differ according to the nature of the threat, with separate pathways having been identified for predator, conspecific and physically harmful threats. In particular, the dorsomedial part of the ventromedial hypothalamus (VHMdm) is critical for the expression of defensive responses to predators. Here, we tested the hypothesis that this circuit also participates in predator fear memory by transient pharmacogenetic inhibition of the VMHdm and its downstream effector, the dorsal periaqueductal grey, during predator fear learning in the mouse. Our data demonstrate that neural activity in the VMHdm is required for both the acquisition and recall of predator fear memory, whereas that of its downstream effector, the dorsal periaqueductal grey, is required only for the acute expression of fear. These findings are consistent with a role for the medial hypothalamus in encoding an internal emotional state of fear. PMID- 26991019 TI - Hydrogen sulfide alleviates uranium-induced acute hepatotoxicity in rats: Role of antioxidant and antiapoptotic signaling. AB - As an endogenous gaseous mediator, H2 S exerts antioxidative, antiapoptotic, and cytoprotective effects in livers. This study was designed to investigate the protective role of H2 S against uranium-induced hepatotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2 S production was determined in livers. The levels of endogenous H2 S and H2 S-producing enzymes (CBS and CSE) were measured in liver homogenates from uranium -intoxicated rats. In rats injected intraperitoneally (i.p.) with uranyl acetate or NaHS (an H2 S donor) alone or in combination, we examined biochemical parameters to assess liver function, revealed hepatic histopathological alteration, investigated oxidative stress markers, and explored apoptotic signaling in liver homogenates. The results suggest that uranium-intoxication in rats decreased CBS and CSE protein expression, H2 S synthesis capacity, and endogenous H2 S generation. NaHS administration in uranium-intoxicated rats produced amelioration in liver biochemical indices and histopathological effects, decreased MDA content, and increased GSH level and antioxidative enzymes activities like SOD, CAT, GPx, and GST. NaHS administration in uranium-intoxicated rats attenuated uranium-activated phosphorylation state of JNK. NaHS treatment in uranium-intoxicated rats increased antiapoptotic Bcl-2 but decreased pro-apoptotic Bax, resulting in the rise of Bcl-2/Bax ratio. NaHS treatment in uranium-intoxicated rats reduced the apoptosis mediator caspase-3 and cytochrome c release and elevated ATP contents. Taken together, these data implicate that H2 S can afford protection to rat livers against uranium-induced adverse effects mediated by up-regulation of antioxidant and antiapoptotic signaling. The anti-apoptotic property of H2 S may be involved, at least in part, in inhibiting JNK signaling. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 581-593, 2017. PMID- 26991020 TI - Importance of margin width in breast-conserving treatment of early breast cancer. AB - BACKGROUND AND METHOD: The association between margin width and ipsilateral breast tumour recurrence (IBTR, defined as invasive recurrence) was investigated in a population-based nationwide cohort of 11,900 patients undergoing breast conserving therapy for invasive cancer. RESULTS: The median follow-up was 4.9 years. The cumulative incidence of IBTR at 5 and 9 years was 2.4% and 5.9%, respectively. A final positive margin increased the risk of IBTR (HR 2.51; 95% CI 1.02-6.23). No decrease in IBTR with a wider negative margin compared to a narrow but negative margin was observed in the adjusted analysis of margin width (>0 to <2 mm vs. >=2 to <5 mm vs. >=5 mm (reference): HR 1.54 (CI 95% 0.81-2.93) vs. 0.95 (CI 95% 0.56-1.62) vs. 1). However, few patients had narrow margins. The factors associated with increased IBTR were young age (P < 0.001), >4 positive lymph nodes (P = 0.008) and re-excision (P = 0.003). A reduced risk of IBTR was observed with chemotherapy (P < 0.001), boost radiation (P = 0.023) and ER positivity (P < 0.001). CONCLUSION: An overall low rate of IBTR was observed. A final positive margin was associated with a more than twofold risk of IBTR. There was no evidence for better local control with wider margins, but the data were insufficient to show whether narrow margins were as good as wider negative margins in terms of local control. J. Surg. Oncol. 2016;113:609-615. (c) 2016 Wiley Periodicals, Inc. PMID- 26991021 TI - Porphyrin Analogues of a Trityl Cation and Anion. AB - Porphyrin-stabilized meso- or beta-carbocations were generated upon treatment of the corresponding bis(4-tert-butylphenyl)porphyrinylcarbinols with trifluoroacetic acid (TFA). Bis(4-tert-butylphenyl)porphyrinylcarbinols were treated with TFA to generate the corresponding carbocations stabilized by a meso- or beta-porphyrinyl group. The meso-porphyrinylmethyl carbocation displayed more effective charge delocalization with decreasing aromaticity compared with the beta-porphyrinylmethyl carbocation. A propeller-like porphyrin trimer, tris(beta porphyrinyl)carbinol, was also synthesized and converted to the corresponding cation that displayed a more intensified absorption reaching over the NIR region. meso-Porphyrinylmethyl carbanion was generated as a stable species upon deprotonation of bis(4-tert-butylphenyl)(meso-porphyrinyl)methane with potassium bis(trimethylsilyl)amide (KHMDS) and [18]crown-6, whereas beta-porphyrinylmethyl anions were highly unstable. PMID- 26991022 TI - Nickel-Catalyzed Carboxylation of Benzylic C-N Bonds with CO2. AB - A user-friendly Ni-catalyzed reductive carboxylation of benzylic C-N bonds with CO2 is described. This procedure outperforms state-of-the-art techniques for the carboxylation of benzyl electrophiles by avoiding commonly observed parasitic pathways, such as homodimerization or beta-hydride elimination, thus leading to new knowledge in cross-electrophile reactions. PMID- 26991023 TI - Acute severe ulcerative colitis: Changing treatment paradigms. PMID- 26991024 TI - Nursing implications: symptom presentation and quality of life in rectal cancer patients. AB - AIMS AND OBJECTIVES: To determine the changes in symptoms experienced by rectal cancer patients during preoperative chemoradiotherapy, with a specific focus on fatigue and to explore how symptoms impact the quality of life. BACKGROUND: Rectal cancer continues to be a healthcare issue internationally, despite advances in management strategies, which includes the administration of preoperative chemoradiotherapy to improve locoregional control. It is known that this treatment may cause adverse effects; however, there is a paucity of literature that specifically examines fatigue, symptoms and quality of life in this patient cohort. DESIGN: A prospective, quantitative correlational design using purposive sampling was adopted. METHODS: Symptoms and quality of life were measured with validated questionnaires in 35 patients at four time points. RESULTS: Symptoms that changed significantly over time as examined using rm-anova include fatigue, bowel function issues, nutritional issues, pain, dermatological issues and urinary function issues. Findings indicate that fatigue leads to poorer quality of life, with constipation, bloating, stool frequency, appetite loss, weight worry, nausea and vomiting, dry mouth and pain also identified as influencing factors on quality of life. CONCLUSION: Findings have highlighted the importance of thorough symptom assessment and management of patients receiving preoperative chemoradiotherapy, particularly midway through treatment, in order to optimise quality of life and minimise interruptions to treatment. RELEVANCE TO CLINICAL PRACTICE: Close monitoring of symptoms during preoperative chemoradiotherapy, particularly at week 4, will enable the implementation of timely interventions so that interruptions to treatment are prevented and the quality of life is optimised, which may hasten postoperative recovery times. PMID- 26991025 TI - Inhibition of platelet aggregation by vanilloid-like agents is not mediated by transient receptor potential vanilloid-1 channels or cannabinoid receptors. AB - Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the individual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of individual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors. PMID- 26991026 TI - Substituted hydroxyapatites for bone regeneration: A review of current trends. AB - At present hydroxyapatite (HA) is been extensively investigated for biomedical applications, largely as a result of its similarity in composition to the mineral portion of bone. Although HA undergoes osseointegration and is bioactive and osteoconductive, the inherent brittleness and low fracture toughness limits its use under load bearing conditions, also once implanted in the body, HA takes a long time to resorb. The crystal structure of HA is conducive to a variety of ionic substitutions. To accurately mimic the calcium deficient and carbonate containing nature of HA in bone, both cationic and anionic substituents have been incorporated to synthetic HA. This article focuses on the incorporation of both the well established (Zn, Si, Sr, F, and carbonate) and latest ions (Ag, citrate, iron, niobate, and tantalates) into the HA structure and aims to highlight the key effects of these substitutions in terms of their chemical, physical, and biological properties. It can be shown that a minor substituent cannot only alter the microstructure, stability and crystallinity of the HA structure in an implant, but also have a significant effect on bone cells colonizing the implant, which in turn can influence the new bone formation and bone remodeling processes. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1285-1299, 2017. PMID- 26991027 TI - Levobupivacaine attenuates lipopolysaccharide-induced acute lung injury. AB - Levobupivacaine (LB), a kind of local anesthetic, possesses anti-inflammatory properties. High-mobility group box 1 (HMGB1), a nuclear DNA-binding protein, plays a key role in the development of acute lung injury (ALI). The aim of this study was to investigate whether LB attenuates ALI by the inhibition of HMGB1 expression and to investigate the molecular mechanisms. ALI in male rats was induced by an intratracheal instillation of LPS (5 mg/kg), and male rats received mini-osmotic pumps containing LB 30 min after LPS exposure. A549 alveolar epithelial cells were incubated with LPS in the presence or absence of LB. An enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines. Western blotting was used to detect the changes in the expression of toll-like receptor 2/4 (TLR2/4) and the activation of NF-kappaB. The results showed that LB significantly protected animals from LPS-induced ALI as evidenced by a decrease in the ratio of lung wet to dry weight, total cells, neutrophils, macrophages, and myeloperoxidase activity, associated with a reduced lung histological damage. We also found that LB post-treatment markedly inhibited the release of HMGB1 and other pro-inflammatory cytokines. Furthermore, LB significantly inhibited LPS-induced TLR2/4 protein overexpression and NF-kappaB activation in the lung tissues and in LPS-stimulated A549 alveolar epithelial cells in vitro. These data indicate that LB attenuated LPS-induced ALI by the inhibition of HMGB1 expression in rats. These benefits were associated with the inhibition of TLR2/4-NF-kappaB pathway by LB. PMID- 26991028 TI - Determination and pharmacokinetic study of four lignans in rat plasma after oral administration of an extract of Valeriana amurensis by ultra-high performance liquid chromatography with tandem mass spectrometry. AB - A selective and sensitive ultra-high performance liquid chromatography with tandem mass spectrometry method was developed and validated for the determination and pharmacokinetic study of (+)-8-hydroxypinoresinol-4'-O-beta -D glucopyranoside, prinsepiol-4-O-beta-D-glucopyranoside, (+)-pinoresinol-4,4'-di-O beta-D-glucopyranoside, and (-)-massoniresinol 3alpha-O-beta-D-glucopyranoside in rat plasma after the oral administration of a Valeriana amurensis extract. The analytes and ethyl 4-hydroxybenzoate (internal standard) were separated on a Waters ACQUITY UPLC HSS T3 chromatographic column. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source operating in negative ionization mode. The linear ranges (ng/mL) of the standard curves were 0.39-154.00, 0.62-244.70, 0.50-198.60, and 0.34-134.50 for (+)-8-hydroxypinoresinol-4'-O-beta-D glucopyranoside, prinsepiol-4-O-beta-D-glucopyranoside, (+)-pinoresinol-4,4'-di-O beta-D-glucopyranoside, and (-)-massoniresinol 3alpha-O-beta-D-glucopyranoside, respectively. The inter- and intra-day precisions were less than 11.0%, the accuracies were between -5.9 and 7.7%, and the extraction recoveries of the four analytes were > 81.2% from rat plasma. The method was successfully applied to a pharmacokinetic study of the four analytes after oral administration of a Valeriana amurensis extract to rats. The developed method has the potential for pharmacokinetic analysis and to provide additional information in the clinical application of Valeriana amurensis. PMID- 26991029 TI - Effect of timolol maleate gel-forming solution on intraocular pressure, pupil diameter, and heart rate in normal and glaucomatous cats. AB - OBJECTIVE: To determine the effects of once-daily topical treatment with timolol maleate gel-forming solution (GFS) on intraocular pressure (IOP), pupil diameter (PD), and heart rate (HR) in normal cats and cats with feline primary congenital glaucoma (FCG). ANIMALS STUDIED AND PROCEDURES: A single drop of timolol maleate 0.5% GFS was administered topically to one randomly assigned eye of 18 adult cats (8 normal, 10 FCG) at 8 am for 8 days; the opposite eye served as the untreated control. IOP was measured in both eyes (OU) every 2 h (PD and HR were measured every 4 h), for 14 h total, 1 day prior to and on days 1 and 8 of treatment. In a second treatment phase, a single drop of timolol was administered at 8 pm for 3 nights and IOP, PD, and HR were measured, as above, beginning at 8 am on day 4. Slit-lamp examinations were conducted prior to and after treatment phases. Comparisons of mean IOP, PD, and HR were made at each time point and between treated and untreated eyes by repeated-measures ANOVA and Tukey-Kramer post hoc test, with P < 0.05 considered significant. RESULTS: Timolol maleate 0.5% GFS had an inconsistent effect on IOP, with maximum IOP-lowering effect (mean = 5.6 mmHg, 17.4%) observed 6 h post-treatment in FCG. The drug caused significant miosis (from 4 to 8 h post-treatment), but had no effect on HR. CONCLUSION: Once-daily application of timolol maleate 0.5% GFS may be of limited clinical benefit in the management of feline congenital glaucoma. PMID- 26991030 TI - Effects of electromagnetic field frequencies on chondrocytes in 3D cell-printed composite constructs. AB - In cartilage tissue engineering, electromagnetic field (EMF) therapy has been reported to have a modest effect on promoting cartilage regeneration. However, these studies were conducted using different frequencies of EMF to stimulate chondrocytes. Thus, it is necessary to investigate the effect of EMF frequency on cartilage formation. In addition to the stimulation, a scaffold is required to satisfy the characteristics of cartilage such as its hydrated and dense extracellular matrix, and a mechanical resilience to applied loads. Therefore, we 3D-printed a composite construct composed of a polymeric framework and a chondrocyte-laden hydrogel. Here, we observed frequency-dependent positive and negative effects on chondrogenesis using a 3D cell-printed cartilage tissue. We found that a frequency of 45 Hz promoted gene expression and secretion of extracellular matrix molecules of chondrocytes. In contrast, a frequency of 7.5 Hz suppressed chondrogenic differentiation in vitro. Additionally, the EMF treated composite constructs prior to implantation showed consistent results with those of in vitro, suggesting that in vitro pre-treatment with different EMF frequencies provides different capabilities for the enhancement of cartilage formation in vivo. This correlation between EMF frequency and 3D-printed chondrocytes suggests the necessity for optimization of EMF parameters when this physical stimulus is applied to engineered cartilage. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1797-1804, 2016. PMID- 26991031 TI - Efficient Regular Perovskite Solar Cells Based on Pristine [70]Fullerene as Electron-Selective Contact. AB - [70]Fullerene is presented as an efficient alternative electron-selective contact (ESC) for regular-architecture perovskite solar cells (PSCs). A smart and simple, well-described solution processing protocol for the preparation of [70]- and [60]fullerene-based solar cells, namely the fullerene saturation approach (FSA), allowed us to obtain similar power conversion efficiencies for both fullerene materials (i.e., 10.4 and 11.4 % for [70]- and [60]fullerene-based devices, respectively). Importantly, despite the low electron mobility and significant visible-light absorption of [70]fullerene, the presented protocol allows the employment of [70]fullerene as an efficient ESC. The [70]fullerene film thickness and its solubility in the perovskite processing solutions are crucial parameters, which can be controlled by the use of this simple solution processing protocol. The damage to the [70]fullerene film through dissolution during the perovskite deposition is avoided through the saturation of the perovskite processing solution with [70]fullerene. Additionally, this fullerene-saturation strategy improves the performance of the perovskite film significantly and enhances the power conversion efficiency of solar cells based on different ESCs (i.e., [60]fullerene, [70]fullerene, and TiO2 ). Therefore, this universal solution processing protocol widens the opportunities for the further development of PSCs. PMID- 26991033 TI - The relationship between cancer incidence, stage and poverty in the United States. AB - We extend a prior analysis on the relation between poverty and cancer incidence in a sample of 2.90 million cancers diagnosed in 16 US states plus Los Angeles over the 2005-2009 period by additionally considering stage at diagnosis. Recognizing that higher relative disparities are often found among less-common cancer sites, our analysis incorporated both relative and absolute measures of disparities. Fourteen of the 21 cancer sites analyzed were found to have significant variation by stage; in each instance, diagnosis at distant stage was more likely among residents of high-poverty areas. If the incidence rates found in the lowest-poverty areas for these 21 cancer sites were applied to the entire country, 18,000 fewer distant-stage diagnoses per year would be expected, a reduction of 8%. Conversely, 49,000 additional local-stage diagnoses per year would be expected, an increase of 4%. These figures, strongly influenced by the most common sites of prostate and female breast, speak to the trade-offs inherent in cancer screening. Integrating the type of analysis presented here into routine cancer surveillance activities would permit a more complete understanding of the dynamic nature of the relationship between socioeconomic status and cancer incidence. PMID- 26991032 TI - Detection of Campylobacter in human and animal field samples in Cambodia. AB - Campylobacter are zoonotic bacteria and a leading cause of human gastroenteritis worldwide with Campylobacter jejuni and C. coli being the most commonly detected species. The aim of this study was to detect Campylobacter in humans and livestock (chickens, ducks, pigs, cattle, water buffalo, quail, pigeons and geese) in rural households by routine culturing and multiplex PCR in faecal samples frozen before analysis. Of 681 human samples, 82 (12%) tested positive by PCR (C. jejuni in 66 samples and C. coli in 16), but none by routine culture. Children were more commonly Campylobacter positive (19%) than adult males (8%) and females (7%). Of 853 livestock samples, 106 (12%) tested positive by routine culture and 352 (41%) by PCR. Campylobacter jejuni was more frequent in chickens and ducks and C. coli in pigs. In conclusion, Campylobacter proved to be highly prevalent by PCR in children (19%), ducks (24%), chickens (56%) and pigs (72%). Routine culturing was insufficiently sensitive in detecting Campylobacter in field samples frozen before analysis. These findings suggest that PCR should be the preferred diagnostic method for detection of Campylobacter in humans and livestock where timely culture is not feasible. PMID- 26991034 TI - The validity of three fall risk screening tools in an acute geriatric inpatient population. AB - AIM: We examined the validity of the Ontario Modified STRATIFY (OM) (St Thomas's Risk Assessment Tool in Falling Elderly Inpatients), The Northern Hospital Modified STRATIFY (TNH) and STRATIFY in predicting falls in an acute aged care unit. METHODS: Data were collected prospectively from 217 people presenting consecutively and falls identified during hospitalisation. RESULTS: Sensitivities of OM (80.0, 95% confidence interval (CI) 58.4 to 91.9%), TNH (85, CI 64.0 to 94.8%) and STRATIFY (80.0, CI 58.4 to 91.0%) were similar. The STRATIFY had higher specificity (61.4, CI 54.5 to 67.9%) than OM (37.1, CI 30.6 to 44.0%) and TNH (51.3, CI 44.3 to 58.2%). Accuracy (percentage of patients correctly classified as 'faller' or 'non-faller') was higher using STRATIFY (63.1, CI 56.5 to 69.3%) and TNH (54.4, CI 47.8 to 61.0%) than with OM (41.0, CI 34.7 to 47.7%, P < 0.0001). CONCLUSION: Screening tools have limited accuracy in identifying patients at high risk of falls. PMID- 26991035 TI - Evolutionary routes to stable ownership. AB - Ownership can evolve in potentially any species. Drawing on insights from across disciplines, we distinguish between possession and ownership and present species neutral criteria for ownership, defined as respect for possession. We use a variant of the tug-of-war evolutionary game to demonstrate how ownership can evolve in the form of a new, biologically realistic strategy, Restraint With Retaliation (RWR). In our game, resource holding potential (RHP) is assumed to be equal between interactants, and resource holding asymmetry determines whether ownership is adaptive. RWR will be evolutionarily stable when the ratio of resource holdings between interactants is relatively low, but not when this ratio is sufficiently high. We offer RWR as one evolutionary route to ownership among many, and discuss how ownership unites previously described behavioural phenomena across taxa. We propose that some but not all mechanisms of territory formation and maintenance can be considered ownership, and show that territories are not the only resources that can be owned. We argue that ownership can be a powerful cooperative solution to tragedies of the commons and problems of collective action throughout the biological world. We advance recent scholarship that has begun to investigate the biological importance of ownership, and we call for a comprehensive account of its evolutionary logic and taxonomic distribution. We propose that ownership should be considered a fundamental, unifying biological phenomenon. PMID- 26991036 TI - Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure. AB - AIMS: The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure. METHODS AND RESULTS: A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 +/- 7%, systolic blood pressure 107 +/- 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient <20 mmHg) showed a worse outcome [hazard ratio (HR) 2.37, 95% confidence interval (CI) 1.12-5.00, P = 0.02]. RV dysfunction [tricuspid annular plane systolic excursion (TAPSE) <=14 mm] in the presence of a low TR gradient identified patients at higher risk of events (HR 2.97, 95% CI 1.19-7.41, P = 0.02). Multivariate analysis showed as best predictors of outcome low RV contraction pressure index (RVCPI), defined as TAPSE * TR gradient, and high estimated right atrial pressure (eRAP). Adding RVCPI (<400 mm*mmHg) and eRAP (>=20 mmHg) to conventional clinical (ADHERE risk tree and NT-proBNP) and echocardiographic risk evaluation resulted in an increase in net reclassification improvement of +19.1% and +20.1%, respectively (P = 0.01) and in c-statistic from 0.59 to 0.73 (P < 0.01). CONCLUSIONS: In acute decompensation of advanced CHF, pulmonary hypertension failed to predict events. The in-hospital and short-term prognosis can be better predicted by eRAP and RVCPI. PMID- 26991038 TI - Factors predicting poor outcomes in T1N0 oral squamous cell carcinoma: indicators for treatment intensification. AB - BACKGROUND: This study investigated the impact of adverse pathological features (APFs) amongst patients with T1N0 oral squamous cell carcinoma (OSCC) on both tumour control and survival. We aimed to investigate clinicopathological factors that would predict poor outcomes and determine a clinically relevant threshold for the recommendation of additional treatment. METHODS: Retrospective analysis of 121 patients from a single institution (1988-2013) who were treated with surgery only (wide local excision of the primary tumour with or without neck dissection). Only patients who are pT1cN0 or pT1pN0 were included. Patients who had received adjuvant radiotherapy were excluded from the study. RESULTS: APFs were associated with increased regional failure included tumour thickness (TT) >=5 mm (P = 0.007), perineural invasion (PNI) (P = 0.003), infiltrative border (P = 0.030) and poor differentiation (P = 0.005). Poorly differentiated tumours were also associated with increased local failure (P = 0.03). Local control (LC), regional control (RC) and disease-specific survival (DSS) decreased with an increasing number of APFs (P = 0.009, P = <0.001 and P = 0.009, respectively). Patients with four or more APFs had significantly worse outcomes in LC (P < 0.001), RC (P < 0.001) and DSS (P < 0.001). CONCLUSION: T1N0 OSCC exhibiting four or more APFs or demonstrating poor differentiation on histology had an increased risk of locoregional failure. The presence of PNI, infiltrative border and TT >=5 mm are associated with increased regional failure. These factors may prompt escalation of treatment for patients with T1N0 OSCC. PMID- 26991037 TI - Multiparametric whole-body anatomic, functional, and metabolic imaging characteristics of peripheral lesions in patients with schwannomatosis. AB - PURPOSE: To describe the anatomic, functional, and metabolic characteristics of peripheral nerve sheath tumors (PNSTs) in patients with schwannomatosis (SWN) on whole-body magnetic resonance imaging (WB-MRI) (anatomic and functional imaging) and fluorine-18-fluorodeoxyglucose positron emission tomography / computed tomography (FDG-PET/CT) (metabolic imaging). MATERIALS AND METHODS: WB-MRIs at 1.5T and 3.0T performed in 13 SWN subjects using short tau inversion recovery (STIR), T1 -weighted (T1 W), contrast-enhanced T1 W, and diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping and FDG-PET/CT were retrospectively reviewed. Two readers reviewed all imaging for the presence and character of peripheral lesions (size, imaging features, ADC values, and standardized uptake values [SUVmax ]) and ancillary findings. Descriptive statistics are reported. RESULTS: In all, 153 index lesions were characterized in 13 patients on WB-MRI. Lesions were characterized as tumors (97% [149/153]) or cysts (3% [4/153]); 96% (143/149) PNSTs were solitary while 4% (6/149) were plexiform. The median size was 2.3 cm (range 1-24.3 cm). On T1 W, 99% (148/149) tumors were homogeneously isointense; on STIR, 81% (121/149) tumors were heterogeneously hyperintense; on postcontrast T1 W, 81% (100/123) tumors enhanced heterogeneously; on DWI, tumor ADC values (*10(-3) mm(2) /s) were variable (minimum ADC range 0.3-2.2, average ADC range 0.9-2.9). The median SUVmax was 6 (range 2.1-11.7) and 10 (2.7-15.3) on early and delayed imaging, respectively. Malignant degeneration was detected in 1% (1/149) with suspicious anatomic, functional, and metabolic characteristics. Ancillary findings included nerve root thickening (23% [3/13]) and spinal canal lesions (15% [2/13]). CONCLUSION: Although the majority of the PNSTs in SWN are benign and solitary, PNSTs can be plexiform, enlarge over time, and, rarely, undergo malignant degeneration. Due to the high metabolic activity in benign PNSTs by FDG-PET/CT in SWN, WB-MRI with functional sequences maybe a more suitable technique for the assessment of disease burden, tumor characterization, and surveillance. J. MAGN. RESON. IMAGING 2016;44:794-803. PMID- 26991039 TI - The Cell Biology of Cytomegalovirus: Implications for Transplantation. AB - Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and gammadelta T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation. PMID- 26991040 TI - Propensity score matching and subclassification in observational studies with multi-level treatments. AB - In this article, we develop new methods for estimating average treatment effects in observational studies, in settings with more than two treatment levels, assuming unconfoundedness given pretreatment variables. We emphasize propensity score subclassification and matching methods which have been among the most popular methods in the binary treatment literature. Whereas the literature has suggested that these particular propensity-based methods do not naturally extend to the multi-level treatment case, we show, using the concept of weak unconfoundedness and the notion of the generalized propensity score, that adjusting for a scalar function of the pretreatment variables removes all biases associated with observed pretreatment variables. We apply the proposed methods to an analysis of the effect of treatments for fibromyalgia. We also carry out a simulation study to assess the finite sample performance of the methods relative to previously proposed methods. PMID- 26991041 TI - Effect of linseed oil supplementation on performance and milk fatty acid composition in dairy cows. AB - Thirty-six Holstein-Friesian crossbred lactating dairy cows were used to determine the effects of linseed oil supplementation on performance and milk fatty acid (FA) profile. Three treatments were as follows: basal diet (56:44 Roughage:concentrate [R:C] ratio, dry matter basis) supplemented with 500 g of palm oil as control (PO), 500 g mixture (1:1, w/w) of palm oil and linseed oil (POLSO) and 500 g of linseed oil (LSO). The LSO supplementation had no effects on total dry matter intake (DMI), milk yield and milk composition. Compared to control cows, cows supplemented with LSO increased milk concentrations of cis 9,trans-11 conjugated linoleic acid (CLA) and n-3 FA (P < 0.05), particularly C18:3n-3, C20:5n-3 and C22:6n-3. Feeding LSO reduced concentrations of milk short and medium-chain saturated fatty acids (P < 0.05) while it increased concentration of milk unsaturated fatty acids (P < 0.05). Milk proportions of n-3 FA increased, whereas n-6/n-3 ratio decreased in the LSO as compared with the control (P < 0.05). In conclusion, supplementing dairy cows' diet based on corn silage with LSO at 500 g/day could improve the nutritional value of milk with potential health-beneficial FA without detrimental effect on milk composition or cow's performance. PMID- 26991042 TI - Direct Observation of Ordered High-Spin-Low-Spin Intermediate States of an Iron(III) Three-Step Spin-Crossover Complex. AB - A neutral mononuclear Fe(III) complex [Fe(III) (H-5-Br-thsa-Me)(5-Br-thsa-Me)]?H2 O (1; H2 -5-Br-thsa-Me=5-bromosalicylaldehyde methylthiosemicarbazone) was prepared that exhibited a three-step spin-crossover (SCO) with symmetry breaking and a 14 K hysteresis loop owing to strong cooperativity. Two ordered intermediate states of 1 were observed, 4HS-2LS and 2HS-4LS, which exhibited reentrant phase-transition behavior. This study provides a new platform for examining multistability in SCO complexes. PMID- 26991044 TI - Multidimensional representation of odors in the human olfactory cortex. AB - What is known as an odor object is an integrated representation constructed from physical features, and perceptual attributes mainly mediated by the olfactory and trigeminal systems. The aim of the present study was to comprehend how this multidimensional representation is organized, by deciphering how similarities in the physical, olfactory and trigeminal perceptual spaces of odors are represented in the human brain. To achieve this aim, we combined psychophysics, functional MRI and multivariate representational similarity analysis. Participants were asked to smell odors diffused by an fMRI-compatible olfactometer and to rate each smell along olfactory dimensions (pleasantness, intensity, familiarity and edibility) and trigeminal dimensions (irritation, coolness, warmth and pain). An event-related design was implemented, presenting different odorants. Results revealed that (i) pairwise odorant similarities in anterior piriform cortex (PC) activity correlated with pairwise odorant similarities in chemical properties (P < 0.005), (ii) similarities in posterior PC activity correlated with similarities in olfactory perceptual properties (P <0.01), and (iii) similarities in amygdala activity correlated with similarities in trigeminal perceptual properties (P < 0.01). These findings provide new evidence that extraction of physical, olfactory and trigeminal features is based on specific fine processing of similarities between odorous stimuli in a distributed manner in the olfactory system. Hum Brain Mapp 37:2161-2172, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991045 TI - Dicumyl Peroxide as a Methylating Reagent in the Ni-Catalyzed Methylation of Ortho C-H Bonds in Aromatic Amides. AB - The direct methylation of ortho C-H bonds in aromatic amides with dicumyl peroxide (DCP) using a nickel complex as the catalyst is reported. The reaction shows a high functional group tolerance and is inhibited by radical scavengers. In reactions of meta-substituted aromatic amides, the reaction proceeds in a highly selective manner at the less hindered C-H bonds. PMID- 26991046 TI - Two-Dimensional Mass Spectrometry for Proteomics, a Comparative Study with Cytochrome c. AB - Two-dimensional Fourier transform ion cyclotron resonance mass spectrometry (2D FT-ICR MS) allows the correlation between precursor and fragment ions in tandem mass spectrometry without the need to isolate the precursor ion beforehand. 2D FT ICR MS has been optimized as a data-independent method for the structural analysis of compounds in complex samples. Data processing methods and denoising algorithms have been developed to use it as an analytical tool. In the present study, the capabilities of 2D FT-ICR MS are explored with a tryptic digest of cytochrome c with both ECD and IRMPD as fragmentation modes. The 2D mass spectra showed useful fragmentation patterns of peptides over a dynamic range of almost 400. By using a quadratic calibration, fragment ion peaks could be successfully assigned. The correlation between precursor and fragment ions in the 2D mass spectra was more accurate than in MS/MS spectra after quadrupole isolation, due to the limitations of quadrupole isolation. The use of the second dimension allowed for successful fragment assignment from precursors that were separated by only m/z 0.0156. The resulting cleavage coverage of cytochrome c almost matched data provided by high-resolution FT-ICR MS/MS analysis, but the 2D FT-ICR MS method required only one experimental scan. PMID- 26991047 TI - Breast atypical microglandular adenosis can be a diagnostic pitfall on fine needle aspiration samples. PMID- 26991048 TI - Monolayer Phases of a Dipolar Perylene Derivative on Au(111) and Surface Potential Build-Up in Multilayers. AB - 9-(Bis-p-tert-octylphenyl)-amino-perylene-3,4-dicarboxy anhydride (BOPA-PDCA) is a strongly dipolar molecule representing a group of asymmetrically substituted perylenes that are employed in dye-sensitized solar cells and hold great promise for discotic liquid crystal applications. Thin BOPA-PDCA films with orientated dipole moments can potentially be used to tune the energy-level alignment in electronic devices and store information. To help assessing these prospects, we here elucidate the molecular self-assembly and electronic structure of BOPA-PCDA employing room temperature scanning tunneling microscopy and spectroscopy in combination with ultraviolet and X-ray photoelectron spectroscopies. BOPA-PCDA monolayers on Au(111) exclusively form in-plane antiferroelectric phases. The molecular arrangements, the increase of the average number of molecules per unit cell via ripening, and the rearrangement upon manipulation with the STM tip indicate an influence of the dipole moment on the molecular assembly and the rearrangement. A slightly preferred out-of-plane orientation of the molecules in the multilayer induces a surface potential of 1.2 eV. This resembles the giant surface potential effect that was reported for vacuum-deposited tris(8 hydroxyquinoline)aluminum and deemed applicable for data storage. Notably, the surface potential in the case of BOPA-PDCA can in part be reversibly removed by visible light irradiation. PMID- 26991049 TI - Interleukin-33 facilitates neutrophil recruitment and bacterial clearance in S. aureus-caused peritonitis. AB - Interleukin (IL)-33, a newly recognized member of IL-1 family of cytokines, plays an important role in polarizing Th2-associated immunity. Recently growing evidence indicates that IL-33 also represents a crucial mediator of antimicrobial infection. In this study, we investigated the effect of IL-33 on antibacterial response using an acute Staphylococcus aureus peritoneal infection model. Our results showed that IL-33 administration induced a rapid bacterial clearance and markedly reduced the S. aureus infection-related mortality. IL-33-treated mice displayed increased neutrophil influx into the focus of infection and higher concentrations of chemokine CXCL2 in the peritoneum than untreated mice. The beneficial effect of IL-33 priming was related to reversal of the S. aureus induced reduction of CXCR2 expression on the surface of neutrophils. Furthermore, conditioning of neutrophils by IL-33 led to the enhancement of complement receptor 3 expression induced by S. aureus, which in turn facilitates the phagocytosis of opsonized S. aureus. Finally, neutrophils primed by IL-33 upregulated the production of reactive oxygen species and the subsequent killing activity for S. aureus. All together, these findings suggest that IL-33, through regulating multiple steps of neutrophil-mediated bactericidal function, provides a profound effect in host antimicrobial defense response. PMID- 26991050 TI - Sulcal Artery Syndrome in a 10-Year-Old Boy. PMID- 26991051 TI - P and Ca requirements for Japanese quail. AB - Four experiments were conducted to estimate the phosphorus and calcium requirements for weight maintenance and weight gain in Japanese quails during their growth phase from 16 to 36 days. Japanese quails aged 16 days were used for estimating the phosphorous and calcium requirements for weight maintenance or weight gain, with these quails composing each reference slaughter group and the others distributed in a completely randomized design, housed in cages of galvanized wire (33 * 33 * 16 cm) that were stored in acclimatized chambers with specific environmental temperatures. The light programme used during the 20-day experimental period was 24 h of artificial light. Analysis of the data showed that the prediction equations for estimating the phosphorus and calcium requirements for weight maintenance and weight gain of Japanese quails between 16 and 36 days of age were P (g/quail/day) = P0.75 *(9.3695 + 7.7397*T) + 9.70*WG, in which P is the phosphorus requirement, and Ca (g/quail/day) = P0.75 *(363.99 - 8.0262*T) + 28.15*WG, in which Ca is the calcium requirement, P is BW (kg), T is temperature ( degrees C) and WG (g/quail/day). PMID- 26991052 TI - Clinical evaluation of a single-reaction real-time RT-PCR for pan-dengue and chikungunya virus detection. AB - BACKGROUND: Dengue virus (DENV) and chikungunya virus (CHIKV) now co-circulate throughout tropical regions of the world, with billions of people living at risk of infection. The differentiation of these infections is important for epidemiologic surveillance as well as clinical care, though widely-used molecular diagnostics for DENV and CHIKV require the performance of two to four separate PCR reactions for detection. OBJECTIVES: In the current study, we sought to develop and evaluate a single-reaction, multiplex real-time RT-PCR (rRT-PCR) for the detection and differentiation of DENV and CHIKV (the pan-DENV-CHIKV rRT-PCR). STUDY DESIGN: From an alignment of all available CHIKV complete genome sequences in GenBank, a new CHIKV rRT-PCR was designed for use in multiplex with a previously described assay for pan-DENV detection. Analytical evaluation was performed in accordance with published recommendations, and the pan-DENV-CHIKV rRT-PCR was clinically compared to reference molecular diagnostics for DENV and CHIKV using 182 serum samples from suspected cases in Managua, Nicaragua. RESULTS: The pan-DENV-CHIKV rRT-PCR had a dynamic range extending from 7.0 to 2.0 log10copies/MUL for each DENV serotype and CHIKV, and the lower limits of 95% detection were 7.9-37.4copies/MUL. The pan-DENV-CHIKV rRT-PCR detected DENV in 81 patients compared to 75 using a reference, hemi-nested DENV RT-PCR, and it demonstrated perfect agreement with a reference CHIKV rRT-PCR (54 positive samples). CONCLUSIONS: The single-reaction, multiplex format of the pan-DENV CHIKV rRT-PCR, combined with sensitive detection of both viruses, has the potential to improve detection while decreasing testing costs and streamlining molecular workflow. PMID- 26991053 TI - A case of relapsing-remitting facial palsy and ipsilateral brachial plexopathy caused by HSV-1. AB - The etiologies of Bell's palsy and brachial neuritis remain uncertain, and the conditions rarely co-occur or reoccur. Here we present a woman in her twenties who had several relapsing-remitting episodes with left-sided facial palsy and brachial neuropathy. The episodes always started with painful left-sided oral blisters. Repeat PCRs HSV-1 DNA from oral vesicular lesions were positive. Extensive screening did not reveal any other underlying cause. Findings on MRI T2 weighted brachial plexus STIR images, using a 3.0-Tesla scanner during an episode, were compatible with brachial plexus neuritis. Except a mannose-binding lectin deficiency, a congenital complement deficiency that is frequently found in the general Caucasian population, no other immunodeficiency was demonstrated in our patient. In vitro resistance to acyclovir was tested negative, but despite prophylactic treatment with the drug in high doses, relapses recurred. To our knowledge, this is the first ever reported documentation of relapsing-remitting facial and brachial plexus neuritis caused by HSV-1. PMID- 26991054 TI - Acute encephalopathy in an immunocompromised boy with astrovirus-MLB1 infection detected by next generation sequencing. AB - We report a case of an immunodeficient 4-year-old boy with acute encephalopathy possibly related to human astrovirus-MLB1 infection. The astrovirus-MLB1 genome was identified in his stool, serum, cerebrospinal fluid, urine, and throat swabs by next generation sequencing. We present additional evidence showing human astroviruses are important infectious agents, regardless of their clades, involving the central nervous system in immunocompromised hosts. PMID- 26991056 TI - Structural characterization of low level degradants in aztreonam injection and an innovative approach to aid HPLC method validation. AB - Three new degradants have been identified from drug product and active pharmaceutical ingredient stability samples of aztreonam, a marketed synthetic monocyclic beta-lactam antibiotic. The degradants were detected following the implementation of a new, more selective HPLC method for the determination of impurities and degradants. The new method was developed in response to changes in the regulatory requirement for mature products. Two of the new unknown Degradants (I and II) were observed in chromatograms from stability samples of aztreonam injection. The third new Degradant (III) was observed during a stability study of the aztreonam active pharmaceutical ingredient. These degradants were structurally characterized. A small amount (ca. 1-3mg) of each degradant was isolated via preparative HPLC for structure elucidation using accurate MS, one and two-dimensional NMR spectroscopy. The small amount of each NMR sample was then reused as a standard for HPLC purity/impurity method validation. Their exact concentrations were determined using quantitative NMR which enabled the execution of the quantitative elements of the HPLC method validation. This innovative approach eliminated the need to isolate or synthesize larger quantities of markers for HPLC/UV method validation, thus saving significant time and reducing costs. PMID- 26991055 TI - Cranberry Product Decreases Fat Accumulation in Caenorhabditis elegans. AB - Cranberry phenolic compounds have been linked to many health benefits. A recent report suggested that cranberry bioactives inhibit adipogenesis in 3T3-L1 adipocytes. Thus, we investigated the effects and mechanisms of the cranberry product (CP) on lipid metabolism using the Caenorhabditis elegans (C. elegans) model. CP (0.016% and 0.08%) dose-dependently reduced overall fat accumulation in C. elegans (N2, wild type) by 43% and 74%, respectively, without affecting its pumping rates or locomotive activities. CP decreased fat accumulation in aak-2 (an ortholog of AMP-activated kinase alpha) and tub-1 (an ortholog of TUBBY) mutants significantly, but only minimal effects were observed in sbp-1 (an ortholog of sterol response element-binding protein-1) and nhr-49 (an ortholog of peroxisome proliferator-activated receptor-alpha) mutant strains. We further confirmed that CP downregulated sbp-1, cebp, and hosl-1 (an ortholog of hormone sensitive lipase homolog) expression, while increasing the expression of nhr-49 in wild-type C. elegans. These results suggest that CP could effectively reduce fat accumulation in C. elegans dependent on sbp-1, cebp, and nhr-49, but not aak 2 and tub-1. PMID- 26991057 TI - Emergence of Human Arboviral Diseases in the Americas, 2000-2016. AB - In addition to individual or clusters of cases of human infections with arboviruses, the past 15 years has seen the emergence of newly recognized arboviruses and the re-emergence of others. Mentioned in this brief summary are Bourbon, Cache Valley, chikungunya, Heartland, Itaqui, Mayaro, Oropouche, Powassan, and Zika viruses, the latter being a remarkable occurrence. PMID- 26991058 TI - Heartwood-specific transcriptome and metabolite signatures of tropical sandalwood (Santalum album) reveal the final step of (Z)-santalol fragrance biosynthesis. AB - Tropical sandalwood (Santalum album) produces one of the world's most highly prized fragrances, which is extracted from mature heartwood. However, in some places such as southern India, natural populations of this slow-growing tree are threatened by over-exploitation. Sandalwood oil contains four major and fragrance defining sesquiterpenols: (Z)-alpha-santalol, (Z)-beta-santalol, (Z)-epi-beta santalol and (Z)-alpha-exo-bergamotol. The first committed step in their biosynthesis is catalyzed by a multi-product santalene/bergamotene synthase. Sandalwood cytochromes P450 of the CYP76F sub-family were recently shown to hydroxylate santalenes and bergamotene; however, these enzymes produced mostly (E)-santalols and (E)-alpha-exo-bergamotol. We hypothesized that different santalene/bergamotene hydroxylases evolved in S. album to stereo-selectively produce (E)- or (Z)-sesquiterpenols, and that genes encoding (Z)-specific P450s contribute to sandalwood oil formation if co-expressed in the heartwood with upstream genes of sesquiterpene biosynthesis. This hypothesis was validated by the discovery of a heartwood-specific transcriptome signature for sesquiterpenoid biosynthesis, including highly expressed SaCYP736A167 transcripts. We characterized SaCYP736A167 as a multi-substrate P450, which stereo-selectively produces (Z)-alpha-santalol, (Z)-beta-santalol, (Z)-epi-beta-santalol and (Z) alpha-exo-bergamotol, matching authentic sandalwood oil. This work completes the discovery of the biosynthetic enzymes of key components of sandalwood fragrance, and highlights the evolutionary diversification of stereo-selective P450s in sesquiterpenoid biosynthesis. Bioengineering of microbial systems using SaCYP736A167, combined with santalene/bergamotene synthase, has potential for development of alternative industrial production systems for sandalwood oil fragrances. PMID- 26991060 TI - Watch and wait after neoadjuvant therapy for rectal cancer. PMID- 26991059 TI - Comparative effectiveness and safety of infliximab and adalimumab in patients with ulcerative colitis. AB - BACKGROUND: Real-world comparative benefits and risks of infliximab (IFX) and adalimumab (ADA) in patients with ulcerative colitis (UC) are unclear. AIM: To evaluate the comparative effectiveness and safety of IFX and ADA in patients with UC who were new users of anti-TNF agents. METHODS: Using an administrative claims database (Optum Labs Data Warehouse), we identified patients who received first anti-TNF (IFX, ADA) prescription after a 12-month period without any anti-TNF treatment (baseline), and with a minimum 6-month follow-up after anti-TNF initiation. Primary outcome measures were: all-cause and UC-related hospitalisation, abdominal surgery, corticosteroid use >60 days after starting anti-TNF, and serious infections. We performed 2:1 propensity-score matched Cox proportional hazard analysis, and inverse probability-of-treatment weight (IPTW) analysis, accounting for healthcare utilisation, comorbidities and use of UC related medication. RESULTS: We included 1400 new users of anti-TNF agents (age, 43 +/- 15 years; 52% males), from 2006 to 2014. On propensity-score matched analysis, there was no significant difference in the risk of UC-related hospitalisation [IFX vs. ADA; adjusted hazard ratio (aHR), 1.04; 95% confidence interval (CI) 0.71-1.51], corticosteroid use (aHR, 0.85; 95% CI, 0.68-1.06) and serious infections (aHR, 0.62; 95% CI, 0.29-1.34) between IFX- and ADA-treated patients; the number of surgical events was very small. On IPTW analysis, risk of corticosteroid use was significantly lower in IFX - as compared to ADA - treated patients (aHR, 0.82; 95% CI, 0.68-0.99). Results were stable on multiple sensitivity analyses. CONCLUSIONS: In a large retrospective cohort of patients with UC who were new users of anti-TNF agents, IFX-treated patients may have lower corticosteroid use than ADA-treated patients, but risk of hospitalisation and serious infections were comparable. PMID- 26991061 TI - Sustained Decrease in Gastroenteritis-related Deaths and Hospitalizations in Children Less Than 5 Years of Age After the Introduction of Rotavirus Vaccination: A Time-Trend Analysis in Brazil (2001-2010). AB - BACKGROUND: Rotavirus (RV) vaccine, Rotarix, was introduced into the Brazil national immunization program in 2006. To estimate population-level vaccine effect, we conducted a time-trend analysis on all-cause gastroenteritis (GE) related death certificate-reported deaths (DCRDs), hospital deaths (HDs) and hospitalizations trends in <5-year-olds before and after RV vaccine introduction. METHODS: National level all-cause GE-related death certificate [Mortality Information System] and admission (Hospital Information System) data were aggregated and analyzed. Negative-binomial regression models (adjusting for age, year and region) compared DCRDs, HDs and hospitalization trends in <5-year-olds between baseline (2001-2005) and postvaccine introduction periods (Mortality Information System: 2007-2009 and Hospital Information System: 2007-2010). Negative-binomial regression models were fitted to data for each outcome before 2006, and the predicted annual frequencies of each outcome were plotted against corresponding observed annual frequencies. RESULTS: During the postvaccine introduction period, there was an overall age-independent GE-related DCRDs reduction (20.9%, P = 0.04) observed in children <5 years of age; a reduction was also seen in infants <1 year of age (20.8%, P = 0.003). Age-independent GE related HDs and hospitalizations reductions (57.1%, P < 0.0001 and 26.6%, P < 0.0001, respectively) were observed in <5-year-olds; HDs reductions were also observed for each age group (<1-year-olds: 55.0%, P < 0.0001 and 1- to <5-year olds: 59.5%, P < 0.0001). Observed annual frequencies of GE-related DCRDs, HDs and hospitalizations were lower than the predicted value in each age group in all years after 2006. CONCLUSIONS: GE-related DCRDs, HDs and hospitalizations were significantly reduced in <1 and in 1- to <5-year-old Brazilian children after Rotarix introduction, which provides additional evidence of the direct and indirect population-level effect of RV vaccination on GE-related mortality and morbidity in children. PMID- 26991062 TI - Lenalidomide as a novel treatment for refractory acquired von Willebrand syndrome associated with monoclonal gammopathy. AB - Essentials Treatment options are limited for refractory bleeding in acquired von Willebrand Syndrome (AVWS). Lenalidomide therapy was studied in two patients with AVWS due to monoclonal gammopathy (MG). Lenalidomide increased von Willebrand factor (VWF), lowered VWF clearance and resolved bleeding. Lenalidomide is a potential treatment option for refractory bleeding in AVWS secondary to MG. SUMMARY: Background Acquired von Willebrand syndrome (AVWS) is associated with lymphoproliferative disorders, including monoclonal gammopathy (MG) of undetermined significance (MGUS) and multiple myeloma. Patients commonly present with significant bleeding complications that are difficult to manage, owing to a markedly reduced von Willebrand factor (VWF) half-life. Objectives To investigate the use of the immunomodulatory drug lenalidomide in two patients with severe refractory bleeding caused by AVWS associated with MGs. Results In both patients, lenalidomide treatment resulted in significant clinical improvement, and marked increases in plasma VWF antigen (VWF:Ag) and VWF ristocetin cofactor levels. This normalization in plasma VWF levels was sustained for > 2 years in both patients. Furthermore, in one patient, plasma VWF levels remain normal for at least 14 months following discontinuation of lenalidomide treatment. To investigate the molecular mechanisms underlying these observations, VWF propeptide (VWFpp)/VWF:Ag ratios were analyzed to assess VWF clearance. At enrolment, plasma VWFpp/VWF:Ag ratios were significantly elevated in both patients. Importantly, lenalidomide treatment resulted in normalization of VWFpp/VWF:Ag ratios in both patients. These novel data suggest that lenalidomide functions to attenuate enhanced VWF clearance in AVWS. Interestingly, in a patient with MGUS, lenalidomide treatment was associated with a significant increase in plasma VWF levels, despite no major change in paraprotein level. Conclusions Collectively, our findings suggest that lenalidomide constitutes a novel therapeutic option for the management of AVWS associated with MG. The biological mechanism(s) through which lenalidomide causes a sustained increase in plasma VWF levels in AVWS independently of paraprotein level requires further study, but is in part modulated through inhibition of enhanced VWF clearance. PMID- 26991063 TI - Engineered Aminoacyl-tRNA Synthetase for Cell-Selective Analysis of Mammalian Protein Synthesis. AB - Methods for cell-selective analysis of proteome dynamics will facilitate studies of biological processes in multicellular organisms. Here we describe a mutant murine methionyl-tRNA synthetase (designated L274GMmMetRS) that charges the noncanonical amino acid azidonorleucine (Anl) to elongator tRNA(Met) in hamster (CHO), monkey (COS7), and human (HeLa) cell lines. Proteins made in cells that express the synthetase can be labeled with Anl, tagged with dyes or affinity reagents, and enriched on affinity resin to facilitate identification by mass spectrometry. The method does not require expression of orthogonal tRNAs or depletion of canonical amino acids. Successful labeling of proteins with Anl in several mammalian cell lines demonstrates the utility of L274GMmMetRS as a tool for cell-selective analysis of mammalian protein synthesis. PMID- 26991065 TI - Individual Face-to-Face Cognitive Behavioural Therapy in Multiple Sclerosis: A Qualitative Study. AB - OBJECTIVE: To investigate how people with multiple sclerosis (MS) experience their participation in individual, face-to-face cognitive behavioural therapy (CBT) aimed at alleviating depressive symptoms. METHOD: Semistructured interviews with 12 participants were conducted after CBT and analyzed using qualitative content analysis. RESULTS: Two main themes emerged: CBT as a demanding process and confronting everyday life after CBT with self-knowledge and well-being. The participants had gained strategies for handling feelings of depression and anxiety. The therapist was considered important for guiding them through the demanding therapy. CONCLUSION: It is important to inform the participants of what CBT entails so that they are mentally prepared for the demanding process and can make the necessary adjustments in their daily life. Knowledge of MS among the therapists as well as collaboration with the multidisciplinary MS care may facilitate participation in CBT. PMID- 26991064 TI - Elucidation of the Dynamics of Transcription Elongation by RNA Polymerase II using Kinetic Network Models. AB - RNA polymerase II (Pol II) is an essential enzyme that catalyzes transcription with high efficiency and fidelity in eukaryotic cells. During transcription elongation, Pol II catalyzes the nucleotide addition cycle (NAC) to synthesize mRNA using DNA as the template. The transitions between the states of the NAC require conformational changes of both the protein and nucleotides. Although X ray structures are available for most of these states, the dynamics of the transitions between states are largely unknown. Molecular dynamics (MD) simulations can predict structure-based molecular details and shed light on the mechanisms of these dynamic transitions. However, the employment of MD simulations on a macromolecule (tens to hundreds of nanoseconds) such as Pol II is challenging due to the difficulty of reaching biologically relevant timescales (tens of microseconds or even longer). For this challenge to be overcome, kinetic network models (KNMs), such as Markov State Models (MSMs), have become a popular approach to access long-timescale conformational changes using many short MD simulations. We describe here our application of KNMs to characterize the molecular mechanisms of the NAC of Pol II. First, we introduce the general background of MSMs and further explain procedures for the construction and validation of MSMs by providing some technical details. Next, we review our previous studies in which we applied MSMs to investigate the individual steps of the NAC, including translocation and pyrophosphate ion release. In particular, we describe in detail how we prepared the initial conformations of Pol II elongation complex, performed MD simulations, extracted MD conformations to construct MSMs, and further validated them. We also summarize our major findings on molecular mechanisms of Pol II elongation based on these MSMs. In addition, we have included discussions regarding various key points and challenges for applications of MSMs to systems as large as the Pol II elongation complex. Finally, to study the overall NAC, we combine the individual steps of the NAC into a five-state KNM based on a nonbranched Brownian ratchet scheme to explain the single-molecule optical tweezers experimental data. The studies complement experimental observations and provide molecular mechanisms for the transcription elongation cycle. In the long term, incorporation of sequence-dependent kinetic parameters into KNMs has great potential for identifying error-prone sequences and predicting transcription dynamics in genome-wide transcriptomes. PMID- 26991066 TI - Generation of Human Lens Epithelial-Like Cells From Patient-Specific Induced Pluripotent Stem Cells. AB - Cataractogenesis begins from the dynamic lens epithelial cells (LECs) and adjacent fiber cells. LECs derived from cell lines cannot maintain the crystalline expression as the primary LECs. The current study aimed to efficiently generate large numbers of human LECs from patient-specific induced pluripotent stem cells (iPSCs). Anterior lens capsules were collected from cataract surgery and were used to culture primary hLECs. iPSCs were induced from these primary hLECs by lentiviral transduction of Oct4, Sox2, Klf4, and c-Myc. Then, the generated iPSCs were re-differentiated into hLECs by the 3-step addition of defined factor combinations (Noggin, BMP4/7, bFGF, and EGF) modified from an established method. During the re-differentiation process, colonies of interest were isolated using a glass picking tool and cloning cylinders based on the colony morphology. After two steps of isolation, populations of LEC-like cells (LLCs) were generated and identified by the expression of lens marker genes by qPCR, western blot and immunofluorescence staining. The study introduced a modified protocol to isolate LLCs from iPSCs by defined factors in a short time frame. This technique could be useful for mechanistic studies of lens-related diseases. J. Cell. Physiol. 231: 2555-2562, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991068 TI - Tectorigenin inhibits osteosarcoma cell migration through downregulation of matrix metalloproteinases in vitro. AB - Tectorigenin (Tec) is an effective component of the traditional Chinese medicine Belamcanda chinensis, which has been reported to exert beneficial effects in various types of cancer. However, the activity and mechanism of Tec in osteosarcoma (OS) have not been investigated to date. The aim of the present study was to examine the inhibitory effect of Tec on OS and its underlying mechanism of action. OS cells (Saos2 and U2OS) were treated with various concentrations of Tec for 24, 48, and 72 h. Cell proliferation was evaluated using an CCK-8 assay. Cell migration and invasion ability were measured using the Transwell assay. The expressions of MMP1, MMP2, MMP9, and cleaved caspase3 were measured using real-time PCR and/or western blot analysis. We found that Tec inhibited the proliferation of OS cells (Saos2 and U2OS) in a dose-dependent and time-dependent manner. In addition, Tec significantly inhibited migration and invasion in OS cells (P<0.05). Tec upregulated the expression of cleaved caspase3, while downregulating the expression of MMP1, MMP2, and MMP9. Taken together, the present study provided fundamental evidence for the application of Tec in chemotherapy against OS. PMID- 26991069 TI - Hair "regrowth" during chemotherapy after scalp cooling technique. PMID- 26991070 TI - A DFT study to unravel the ligand exchange kinetics and thermodynamics of Os(VIII) oxo/hydroxido/aqua complexes in aqueous matrices. AB - The Os(VIII) oxo/hydroxido complexes that are abundant in mild to relatively concentrated basic aqueous solutions are Os(VIII)O4, [Os(VIII)O4(OH)](-) and two cis-[Os(VIII)O4(OH)2](2-) species. Os(VIII) complexes that contain water ligands are thermodynamically unfavoured w.r.t. the abovementioned species. Os(VIII)O4 reacts with hydroxide in two, consecutive, elementary coordination sphere expansion steps to form the [Os(VIII)O4(OH)](-) complex and then the cis [Os(VIII)O4(OH)2](2-) species. The Gibbs energy of activation for both reactions, in the forward and reverse direction, are in the range of 6-12 kcal mol(-1) and are relatively close to diffusion-controlled. The thermodynamic driving force of the first reaction is the bonding energy of the Os(VIII)-OH metal-hydroxido ligand, while of the second reaction it is the relatively large hydration energy of the doubly-charged cis-[Os(VIII)O4(OH)2](2-) product compared to the singly charged reactants. The DFT-calculated (PBE-D3 functional) in the simulated aqueous phase (COSMO) is -2.4 kcal mol(-1) for the first reaction and -0.6 kcal mol(-1) for the second reaction and agree to within 1 kcal mol(-1) with reported experimental values, at -2.7 and 0.3 kcal mol(-1) respectively. From QTAIM and EDA analyses it is deduced that the Os(VIII)[double bond, length as m-dash]O bonding interactions are ionic (closed-shell) and that Os(VIII)-OH bonding interactions are polar covalent (dative). In contrast to QTAIM, NCI analysis allowed for the identification of relatively weak intramolecular hydrogen bonding interactions between neighbouring oxo and hydroxido ligands in both [Os(VIII)O4(OH)](-) and cis-[Os(VIII)O4(OH)2](2-) complexes. PMID- 26991067 TI - A Longitudinal Analysis of Outcomes of Lupus Nephritis in an International Inception Cohort Using a Multistate Model Approach. AB - OBJECTIVE: To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach. METHODS: Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30-60 ml/minute), or state 3 (<30 ml/minute) and estimated proteinuria state 1 (<0.25 gm/day), state 2 (0.25 3.0 gm/day), or state 3 (>3.0 gm/day), or end-stage renal disease (ESRD) or death. Using multistate modeling, relative transition rates between states indicated improvement and deterioration. RESULTS: Of 1,826 lupus patients, 700 (38.3%) developed LN. During a mean +/- SD follow-up of 5.2 +/- 3.5 years, the likelihood of improvement in estimated GFR and estimated proteinuria was greater than the likelihood of deterioration. After 5 years, 62% of patients initially in estimated GFR state 3 and 11% of patients initially in estimated proteinuria state 3 transitioned to ESRD. The probability of remaining in the initial states 1, 2, and 3 was 85%, 11%, and 3%, respectively, for estimated GFR and 62%, 29%, and 4%, respectively, for estimated proteinuria. Male sex predicted improvement in estimated GFR states; older age, race/ethnicity, higher estimated proteinuria state, and higher renal biopsy chronicity scores predicted deterioration. For estimated proteinuria, race/ethnicity, earlier calendar years, damage scores without renal variables, and higher renal biopsy chronicity scores predicted deterioration; male sex, presence of lupus anticoagulant, class V nephritis, and mycophenolic acid use predicted less improvement. CONCLUSION: In LN, the expected improvement or deterioration in renal outcomes can be estimated by multistate modeling and is preceded by identifiable risk factors. New therapeutic interventions for LN should meet or exceed these expectations. PMID- 26991071 TI - Rapid Assembly of Heterogeneous 3D Cell Microenvironments in a Microgel Array. AB - Heterogeneous 3D cell microenvironment arrays are rapidly assembled by combining surface-wettability-guided assembly and microdroplet-array-based operations. This approach enables precise control over individual shapes, sizes, chemical concentrations, cell density, and 3D spatial distribution of multiple components. This technique provides a cost-effective solution to meet the increasing demand of stem cell research, tissue engineering, and drug screening. PMID- 26991072 TI - Comparing the sensitivity of chlorophytes, cyanobacteria, and diatoms to major use antibiotics. AB - The occurrence of antibiotic residues in the aquatic environment is an emerging concern. In contrast to daphnia and fish, algae are known to be particularly sensitive to antibiotic exposure. However, to date, a systematic evaluation of the sensitivity of different algal species to antibiotics has not been performed. The aim of the present study was therefore to explore the sensitivity of a battery of algal species toward antibiotic exposures. The present study investigated the growth inhibition effects of 3 major-use antibiotics, tylosin, lincomycin, and trimethoprim, on 7 algal species from the chlorophyte, cyanobacteria, and diatom groups. Based on median effective concentration (EC50) values, cyanobacteria (EC50 = 0.095-0.13 MUmol/L) were found to be the most sensitive group to lincomycin followed by chlorophytes (EC50 = 7.36-225.73 MUmol/L) and diatoms (EC50 > 225.73 MUmol/L). Cyanobacteria were also the most sensitive group to tylosin (EC50 = 0.09-0.092 MUmol/L), but, for this compound, diatoms (EC50 = 1.33-5.7 MUmol/L) were more sensitive than chlorophytes (EC50 = 4.14-81.2 MUmol/L). Diatoms were most sensitive to trimethoprim (EC50 = 7.36 74.61 MUmol/L), followed by cyanobacteria (EC50 = 315.78-344.45 MUmol/L), and chlorophytes (EC50 > 344.45 MUmol/L) for trimethoprim. Although these results partly support the current approach to regulatory environmental risk assessment (whereby cyanobacterial species are recommended for use with antibiotic compounds), they indicate that for some antibiotics this group might not be the most appropriate test organism. It is therefore suggested that environmental risk assessments consider data on 3 algal groups (chlorophytes, cyanobacteria, and diatoms) and use test species from these groups, which are consistently found to be the most sensitive (Pseudokirchneriella subcapitata, Anabaena flos-aquae, and Navicula pelliculosa). Environ Toxicol Chem 2016;35:2587-2596. (c) 2016 SETAC. PMID- 26991073 TI - Preconditioning with recombinant high-mobility group box 1 induces ischemic tolerance in a rat model of focal cerebral ischemia-reperfusion. AB - Preconditioning with ligands of toll-like receptors (TLRs) is a powerful neuroprotective approach whereby a low dose of stimulus confers significant protection against subsequent substantial brain damage by reprogramming the ischemia-activated TLRs signaling. Herein, we aim to explore whether preconditioning with recombinant high-mobility group box 1 (rHMGB1), one of the TLRs ligands, decreases cerebral ischemia-reperfusion injury (IRI). Rats were intracerebroventricularly pretreated with rHMGB1, 1 or 3 days before induction of middle cerebral artery occlusion. Results showed that preconditioning with rHMGB1 1 day, but not 3 days, prior to ischemia dramatically reduced neurological deficits, infarct size, brain swelling, cell apoptosis, and blood-brain barrier permeability. Interleukin-1R-associated kinase-M (IRAK-M), a critical negative regulator of TLRs signaling, was robustly increased in response to brain IRI and was further elevated by rHMGB1 pretreatment, indicating its role associated with the rHMGB1 preconditioning-mediated ischemic tolerance. In vitro and in vivo assays indicated that the induced IRAK-M expression was localized in microglia. In addition, TLR4 specific inhibitor TAK-242 abolished the neuroprotective effects and the induction of IRAK-M offered by rHMGB1 preconditioning. Collectively, our study demonstrates that rHMGB1 preconditioning is neuroprotective during cerebral IRI, which is associated with activated TLR4/IRAK M signaling in microglia. We found that high-mobility group box 1 (HMGB1) pretreatment conditioned the brain against subsequent ischemia-reperfusion injury. We propose the following mechanism for HMGB1 preconditioning-mediated ischemic tolerance: through toll-like receptor TLR4, HMGB1 preconditioning magnifies the up-regulation of interleukin-1R-associated kinase-M (IRAK-M) induced by ischemia-reperfusion in microglia, resulting in the decreased phosphorylation of IRAK-1. These findings are helpful in understanding the endogenous mechanisms that counteract ischemic insults. PMID- 26991075 TI - Hippocampal alpha-synuclein and interneurons in Parkinson's disease: Data from human and mouse models. AB - BACKGROUND: Dementia is a nonmotor feature of Parkinson's disease, arising around the onset of hippocampal pathology in stage IV of the disease, from where it progress to the isocortex. Differential alpha-synuclein involvement in hippocampal interneuron populations remains unknown. The objective of this study was to analyze the involvement of alpha-synuclein in hippocampal interneurons in an alpha-synucleinopathy mouse model and in the brains of Parkinson's disease patients. METHODS: The distribution of alpha-synuclein was examined in the dentate gyrus and CA1, CA2, and CA3 fields of the hippocampus in A53T transgenic mice at 16, 30, 43, and 56 weeks and in Parkinson's disease patients at neuropathological stages III, IV, and V. Expression of interneuron markers (mouse: calbindin, calretinin, and somatostatin; human: parvalbumin and somatostatin) were quantified and compared. Coexpression of these markers with alpha-synuclein was analyzed. RESULTS: In mice, alpha-synuclein expression was most concentrated in the granular and polymorphic layers of the dentate gyrus and in the CA2 and CA3 fields. Expression significantly increased at 30 and 43 weeks and then significantly decreased at 56 weeks. In human brains, a significantly higher density of alpha-synuclein was observed in the CA2. The expression of interneuron markers was, in general, not significantly different between control and transgenic animals, except in calbindin and somatostatin at 43 weeks. The alpha-synuclein protein colocalized with somatostatin and calbindin in the mouse hippocampus and with parvalbumin in the human hippocampus. CONCLUSIONS: The differential alpha-synucleinopathy of hippocampal interneuron populations may help in the study of mechanisms of protein aggregation and progression relevant to PD and PD dementia. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26991074 TI - Viable influenza A virus in airborne particles expelled during coughs versus exhalations. AB - BACKGROUND: To prepare for a possible influenza pandemic, a better understanding of the potential for the airborne transmission of influenza from person to person is needed. OBJECTIVES: The objective of this study was to directly compare the generation of aerosol particles containing viable influenza virus during coughs and exhalations. METHODS: Sixty-one adult volunteer outpatients with influenza like symptoms were asked to cough and exhale three times into a spirometer. Aerosol particles produced during coughing and exhalation were collected into liquid media using aerosol samplers. The samples were tested for the presence of viable influenza virus using a viral replication assay (VRA). RESULTS: Fifty three test subjects tested positive for influenza A virus. Of these, 28 (53%) produced aerosol particles containing viable influenza A virus during coughing, and 22 (42%) produced aerosols with viable virus during exhalation. Thirteen subjects had both cough aerosol and exhalation aerosol samples that contained viable virus, 15 had positive cough aerosol samples but negative exhalation samples, and 9 had positive exhalation samples but negative cough samples. CONCLUSIONS: Viable influenza A virus was detected more often in cough aerosol particles than in exhalation aerosol particles, but the difference was not large. Because individuals breathe much more often than they cough, these results suggest that breathing may generate more airborne infectious material than coughing over time. However, both respiratory activities could be important in airborne influenza transmission. Our results are also consistent with the theory that much of the aerosol containing viable influenza originates deep in the lungs. PMID- 26991077 TI - Identification of IgH gene rearrangement and immunophenotype in an animal model of Epstein-Barr virus-associated lymphomas. AB - Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma. Because the susceptible hosts of EB virus are limited to human and cotton-top tamarins (Saguinus oedipus), there have been no appropriate animal models until the lymphoma model induced by EBV in human peripheral blood lymphocyte (hu-PBL)/SCID chimeric mice was reported. However, it is still controversial whether the EBV-associated lymphoma induced in hu-PBL/SCID mice is a monoclonal tumor. In this study, we transplanted normal human peripheral blood lymphocytes (hu-PBL) from six donors infected with EBV into SCID mice to construct hu-PBL/SCID chimeric mice. The induced tumors were found in the mediastinum or abdominal cavity of SCID mice. Microscopic observation exhibited tumor cells that were large and had a plasmablastic, centroblastic or immunoblastic-like appearance. Immunophenotyping assays showed the induced tumors were LCA-positive, CD20/CD79a-positive (markers of B cells), and CD3/CD45RO negative (markers of T cells). A human-specific Alu sequence could be amplified by Alu-PCR. This confirmed that induced tumors were B-cell lymphomas originating from the transplanted human lymphocytes rather than mouse cells. EBER in situ hybridization detected positive signals in the nuclei of the tumor cells. Expression of EBV-encoded LMP1, EBNA-1, and EBNA-2 in the tumors was significantly positive. PCR-based capillary electrophoresis analysis of IgH gene rearrangement revealed a monoclonal peak and single amplification product in all six cases of induced tumors. This indicated that EBV can induce monoclonal proliferation of human B lymphocytes and promotes the development of lymphoma. J. Med. Virol. 88:1804-1813, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991076 TI - A default method to specify skeletons for Bayesian model averaging continual reassessment method for phase I clinical trials. AB - The Bayesian model averaging continual reassessment method (CRM) is a Bayesian dose-finding design. It improves the robustness and overall performance of the continual reassessment method (CRM) by specifying multiple skeletons (or models) and then using Bayesian model averaging to automatically favor the best-fitting model for better decision making. Specifying multiple skeletons, however, can be challenging for practitioners. In this paper, we propose a default way to specify skeletons for the Bayesian model averaging CRM. We show that skeletons that appear rather different may actually lead to equivalent models. Motivated by this, we define a nonequivalence measure to index the difference among skeletons. Using this measure, we extend the model calibration method of Lee and Cheung (2009) to choose the optimal skeletons that maximize the average percentage of correct selection of the maximum tolerated dose and ensure sufficient nonequivalence among the skeletons. Our simulation study shows that the proposed method has desirable operating characteristics. We provide software to implement the proposed method. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991079 TI - Combining existing numerical models with data assimilation using weighted least squares finite element methods. AB - A new approach has been developed for combining and enhancing the results from an existing computational fluid dynamics model with experimental data using the weighted least-squares finite element method (WLSFEM). Development of the approach was motivated by the existence of both limited experimental blood velocity in the left ventricle and inexact numerical models of the same flow. Limitations of the experimental data include measurement noise and having data only along a two-dimensional plane. Most numerical modeling approaches do not provide the flexibility to assimilate noisy experimental data. We previously developed an approach that could assimilate experimental data into the process of numerically solving the Navier-Stokes equations, but the approach was limited because it required the use of specific finite element methods for solving all model equations and did not support alternative numerical approximation methods. The new approach presented here allows virtually any numerical method to be used for approximately solving the Navier-Stokes equations, and then the WLSFEM is used to combine the experimental data with the numerical solution of the model equations in a final step. The approach dynamically adjusts the influence of the experimental data on the numerical solution so that more accurate data are more closely matched by the final solution and less accurate data are not closely matched. The new approach is demonstrated on different test problems and provides significantly reduced computational costs compared with many previous methods for data assimilation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991078 TI - Sporadic Retinoblastoma and Parental Smoking and Alcohol Consumption before and after Conception: A Report from the Children's Oncology Group. AB - BACKGROUND: Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic) retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception) contribute to the two phenotypes (bilateral or unilateral) of sporadic retinoblastoma. METHODS: Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children's Oncology Group. Controls (n = 424) were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma. FINDINGS: Maternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR), 8.9; 95% confidence interval (CI) 1.5-51, and unconditional OR, 2.4; 95% CI, 1.3-4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5-20.8, and unconditional OR, 2.8; 95% CI, 1.1-7.0. No association was found for maternal or paternal alcohol consumption. CONCLUSION: The results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors. PMID- 26991084 TI - Cell division: TIPs for shaping Aurora B activity. PMID- 26991087 TI - Corrigendum: Frequency and amplitude control of cortical oscillations by phosphoinositide waves. PMID- 26991088 TI - Corrigendum: SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. PMID- 26991085 TI - Toxin-antitoxin systems in bacterial growth arrest and persistence. AB - Bacterial persister cells constitute a subpopulation of genetically identical, metabolically slow-growing cells that are highly tolerant of antibiotics and other environmental stresses. Recent studies have demonstrated that gene loci known as toxin-antitoxin (TA) modules play a central role in the persister state. Under normal growth conditions, antitoxins potently inhibit the activities of the toxins. In contrast, under conditions of stress, the antitoxins are selectively degraded, freeing the toxins to inhibit essential cellular processes, such as DNA replication and protein translation. This inhibition results in rapid growth arrest. In this Review, we highlight recent discoveries of these multifaceted TA systems with a focus on the newly uncovered mechanisms, especially conditional cooperativity, that are used to regulate cell growth and persistence. We also discuss the potential for targeting TA systems for antimicrobial drug discovery. PMID- 26991090 TI - Genetic variations (Arg5Pro and Leu6Pro) modulate the structure and activity of GPX1 and genetic risk for vitiligo. PMID- 26991091 TI - The use of noninvasive prenatal testing in obstetric care: educational resources, practice patterns, and barriers reported by a national sample of clinicians. AB - OBJECTIVE: The aim of this study was to identify how physicians develop their knowledge base and practice patterns regarding noninvasive prenatal testing (NIPT). METHODS: A survey was used to assess physicians' informational sources and practice patterns regarding NIPT. RESULTS: While most of the 258 participants acquire knowledge about NIPT from the medical literature or didactic educational programming, 74 (28.7%) cite commercial laboratories as an initial source and 124 (47.8%) as a way to keep current with changes in NIPT. About one-third (n = 94, 36.4%) seek information about ethical issues related to NIPT. Half of the OB/GYN respondents (n = 136, 52.7%) provide pretest counseling; fewer refer to a genetic counselor or maternal fetal medicine specialist (MFM) (n = 94, 34.6%, n = 29, 11.2%, respectively). Pretest counseling content and the comfort with which participants discuss topics pertinent to patients' utilization of NIPT varied between OB/GYNs and MFMs. CONCLUSIONS: Advances in cff DNA technology emphasize the need for effective strategies for physicians to develop competency and practice patterns regarding NIPT. Study findings speak to the need for effective educational resources for obstetric providers, not just early adopters of NIPT but also for primary OB/GYNs as they serve in the role of the first point of contact for women considering their prenatal testing options. (c) 2016 John Wiley & Sons, Ltd. PMID- 26991093 TI - Mechanistic Study on Oxorhenium-Catalyzed Deoxydehydration and Allylic Alcohol Isomerization. AB - The reaction mechanism of 1,2*n-deoxydehydration (DODH; n=1, 2, 3 ...) reactions with 1-butanol as a reductant in the presence of methyltrioxorhenium(VII) catalyst has been investigated by DFT. The reduced rhenium compound, methyloxodihydroxyrhenium(V), serves as the catalytically relevant species in both allylic alcohol isomerization and subsequent DODH processes. Compared with three-step pathway A, involving [1,3]-transposition of allylic alcohols, direct two-step pathway B is an alternative option with lower activation barriers. The rate-limiting step of the DODH reaction is the first hydrogen transfer in methyltrioxorhenium(VII) reduction. Moreover, the increase in the distance between two hydroxyl groups in direct 1,2*n-DODH reactions for C4 and C6 diols results in a higher barrier height. PMID- 26991092 TI - Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread. AB - Skin infection with the poxvirus vaccinia (VV) elicits a powerful, inflammatory cellular response that clears virus infection in a coordinated, spatially organized manner. Given the high concentration of pro-inflammatory effectors at areas of viral infection, it is unclear how tissue pathology is limited while virus-infected cells are being eliminated. To better understand the spatial dynamics of the anti-inflammatory response to a cutaneous viral infection, we first screened cytokine mRNA expression levels after epicutaneous (ec.) VV infection and found a large increase the anti-inflammatory cytokine IL-10. Ex vivo analyses revealed that T cells in the skin were the primary IL-10-producing cells. To understand the distribution of IL-10-producing T cells in vivo, we performed multiphoton intravital microscopy (MPM) of VV-infected mice, assessing the location and dynamic behavior of IL-10 producing cells. Although virus specific T cells were distributed throughout areas of the inflamed skin lacking overt virus-infection, IL-10+ cells closely associated with large keratinocytic foci of virus replication where they exhibited similar motility patterns to bulk antigen-specific CD8+ T cells. Paradoxically, neutralizing secreted IL-10 in vivo with an anti-IL-10 antibody increased viral lesion size and viral replication. Additional analyses demonstrated that IL-10 antibody administration decreased recruitment of CCR2+ inflammatory monocytes, which were important for reducing viral burden in the infected skin. Based upon these findings, we conclude that spatially concentrated IL-10 production limits cutaneous viral replication and dissemination, likely through modulation of the innate immune repertoire at the site of viral growth. PMID- 26991095 TI - Reply. PMID- 26991094 TI - Detection of Coxiella burnetii in Ambient Air after a Large Q Fever Outbreak. AB - One of the largest Q fever outbreaks ever occurred in the Netherlands from 2007 2010, with 25 fatalities among 4,026 notified cases. Airborne dispersion of Coxiella burnetii was suspected but not studied extensively at the time. We investigated temporal and spatial variation of Coxiella burnetii in ambient air at residential locations in the most affected area in the Netherlands (the South East), in the year immediately following the outbreak. One-week average ambient particulate matter < 10 MUm samples were collected at eight locations from March till September 2011. Presence of Coxiella burnetii DNA was determined by quantitative polymerase chain reaction. Associations with various spatial and temporal characteristics were analyzed by mixed logistic regression. Coxiella burnetii DNA was detected in 56 out of 202 samples (28%). Airborne Coxiella burnetii presence showed a clear seasonal pattern coinciding with goat kidding. The spatial variation was significantly associated with number of goats on the nearest goat farm weighted by the distance to the farm (OR per IQR: 1.89, CI: 1.31-2.76). We conclude that in the year after a large Q fever outbreak, temporal variation of airborne Coxiella burnetii is suggestive to be associated with goat kidding, and spatial variation with distance to and size of goat farms. Aerosol measurements show to have potential for source identification and attribution of an airborne pathogen, which may also be applicable in early stages of an outbreak. PMID- 26991096 TI - Our Advisors, Our Ambassadors, Our Editorial Board Members. PMID- 26991098 TI - Capturing the Structure of the Substrate Bound Condensation Domain. AB - Condensation domains of nonribosomal peptide synthetase machineries have so far escaped detailed structural analysis. In this issue of Cell Chemical Biology, Bloudoff et al. (2016) describe a protein tethering technique that allowed the authors to obtain structural information on the substrate bound state of the first condensation domain from calcium-dependent antibiotic biosynthesis, thus opening a new window into how these important biosynthetic machineries function. PMID- 26991099 TI - Understanding the Collective Nose of Bacteria. AB - Bacteria use a rich chemical vocabulary to "smell out" environmental conditions and communicate with each other about what is going on. This helps them optimize their virulence and attack differently, depending on whether they are, for example, in the lungs or the gut. In this issue of Cell Chemical Biology, Welsh and Blackwell (2016) start to unravel this complexity using chemical probes and offer insights into how we might start targeting these processes in a new way. PMID- 26991100 TI - Posttranslational Peptide-Modification Enzymes in Action: Key Roles for Leaders and Glutamate. AB - In this issue of Cell Chemical Biology, Ortega et al. (2016) determine the structure of another lantibiotic dehydratase with a tRNA(Glu)-dependent mechanism of modification. Moreover, they identify a common recognition motif involved in leader peptide binding in a number of different peptide-modification enzymes. These findings open up new mining possibilities and allow novel approaches in peptide engineering. PMID- 26991101 TI - Blending Quadruplexes and Bordeaux: A Grand Cru! AB - The Fifth International Meeting on Quadruplex Nucleic Acids took place in Bordeaux, France. Over the course of three intense days in May 2015, the quadruplex community had an opportunity to share exciting developments in the field, especially key insights into emerging biological roles that these structures, considered for decades to be nothing more but in vitro curiosity, are playing. PMID- 26991102 TI - Chemical Probes Allow Structural Insight into the Condensation Reaction of Nonribosomal Peptide Synthetases. AB - Nonribosomal peptide synthetases (NRPSs) synthesize a vast variety of small molecules, including antibiotics, antitumors, and immunosuppressants. The NRPS condensation (C) domain catalyzes amide bond formation, the central chemical step in nonribosomal peptide synthesis. The catalytic mechanism and substrate determinants of the reaction are under debate. We developed chemical probes to structurally study the NRPS condensation reaction. These substrate analogs become covalently tethered to a cysteine introduced near the active site, to mimic covalent substrate delivery by carrier domains. They are competent substrates in the condensation reaction and behave similarly to native substrates. Co-crystal structures show C domain-substrate interactions, and suggest that the catalytic histidine's principle role is to position the alpha-amino group for nucleophilic attack. Structural insight provided by these co-complexes also allowed us to alter the substrate specificity profile of the reaction with a single point mutation. PMID- 26991103 TI - RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance. AB - Antibiotic resistance arises from the maintenance of resistance mutations or genes acquired from the acquisition of adaptive de novo mutations or the transfer of resistance genes. Antibiotic resistance is acquired in response to antibiotic therapy by activating SOS-mediated DNA repair and mutagenesis and horizontal gene transfer pathways. Initiation of the SOS pathway promotes activation of RecA, inactivation of LexA repressor, and induction of SOS genes. Here, we have identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response. These inhibitors potentiate the activity of bactericidal antibiotics, including members of the quinolone, beta-lactam, and aminoglycoside families in both Gram-negative and Gram-positive bacteria. They reduce the ability of bacteria to acquire antibiotic resistance mutations and to transfer mobile genetic elements conferring resistance. This study highlights the advantage of including RecA inhibitors in bactericidal antibiotic therapies and provides a new strategy for prolonging antibiotic shelf life. PMID- 26991104 TI - A Molecular Mechanism for Sequential Activation of a G Protein-Coupled Receptor. AB - Ligands targeting G protein-coupled receptors (GPCRs) are currently classified as either orthosteric, allosteric, or dualsteric/bitopic. Here, we introduce a new pharmacological concept for GPCR functional modulation: sequential receptor activation. A hallmark feature of this is a stepwise ligand binding mode with transient activation of a first receptor site followed by sustained activation of a second topographically distinct site. We identify 4-CMTB (2-(4-chlorophenyl)-3 methyl-N-(thiazol-2-yl)butanamide), previously classified as a pure allosteric agonist of the free fatty acid receptor 2, as the first sequential activator and corroborate its two-step activation in living cells by tracking integrated responses with innovative label-free biosensors that visualize multiple signaling inputs in real time. We validate this unique pharmacology with traditional cellular readouts, including mutational and pharmacological perturbations along with computational methods, and propose a kinetic model applicable to the analysis of sequential receptor activation. We envision this form of dynamic agonism as a common principle of nature to spatiotemporally encode cellular information. PMID- 26991107 TI - Asymmetric Synthesis of Chiral Atropisomeric Bis-Aryl Organophosphorus from Menthyl H-Phosphinate. AB - This review describes new methods for the synthesis of chiral monophosphine ligands with menthyl phenylphosphinate as a chiral auxiliary through asymmetric Suzuki-Miyaura cross-coupling reactions and asymmetric C-H functionalization. The chiral menthyl phenylphosphinate as a chiral auxiliary is easy to prepare and the menthyl group can easily be transformed into other functional groups, with the chiral center synchronously remaining. These methodologies provide highly efficient and practical strategies for the synthesis of novel axially chiral biaryl monophosphine oxides and their corresponding phosphines. Meanwhile, these reactions are easy to handle and exhibit wide scope for substrates with excellent diastereomeric ratios. PMID- 26991105 TI - Attenuating Listeria monocytogenes Virulence by Targeting the Regulatory Protein PrfA. AB - The transcriptional activator PrfA, a member of the Crp/Fnr family, controls the expression of some key virulence factors necessary for infection by the human bacterial pathogen Listeria monocytogenes. Phenotypic screening identified ring fused 2-pyridone molecules that at low micromolar concentrations attenuate L. monocytogenes cellular uptake by reducing the expression of virulence genes. These inhibitors bind the transcriptional regulator PrfA and decrease its affinity for the consensus DNA-binding site. Structural characterization of this interaction revealed that one of the ring-fused 2-pyridones, compound 1, binds at two separate sites on the protein: one within a hydrophobic pocket or tunnel, located between the C- and N-terminal domains of PrfA, and the second in the vicinity of the DNA-binding helix-turn-helix motif. At both sites the compound interacts with residues important for PrfA activation and helix-turn-helix formation. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes. PMID- 26991106 TI - Effect of Temperature Downshift on the Transcriptomic Responses of Chinese Hamster Ovary Cells Using Recombinant Human Tissue Plasminogen Activator Production Culture. AB - Recombinant proteins are widely used as biopharmaceuticals, but their production by mammalian cell culture is expensive. Hence, improvement of bioprocess productivity is greatly needed. A temperature downshift (TDS) from 37 degrees C to 28-34 degrees C is an effective strategy to expand the productive life period of cells and increase their productivity (qp). Here, TDS in Chinese hamster ovary (CHO) cell cultures, initially grown at 37 degrees C and switched to 30 degrees C during the exponential growth phase, resulted in a 1.6-fold increase in the qp of recombinant human tissue plasminogen activator (rh-tPA). The transcriptomic response using next-generation sequencing (NGS) was assessed to characterize the cellular behavior associated with TDS. A total of 416 (q > 0.8) and 3,472 (q > 0.9) differentially expressed transcripts, with more than a 1.6-fold change at 24 and 48 h post TDS, respectively, were observed in cultures with TDS compared to those at constant 37 degrees C. In agreement with the extended cell survival resulting from TDS, transcripts related to cell growth arrest that controlled cell proliferation without the activation of the DNA damage response, were differentially expressed. Most upregulated genes were related to energy metabolism in mitochondria, mitochondrial biogenesis, central metabolism, and avoidance of apoptotic cell death. The gene coding for rh-tPA was not differentially expressed, but fluctuations were detected in the transcripts encoding proteins involved in the secretory machinery, particularly in glycosylation. Through NGS the dynamic processes caused by TDS were assessed in this biological system. PMID- 26991108 TI - Estimation of Mycobacterium avium subsp. paratuberculosis load in raw bulk tank milk in Emilia-Romagna Region (Italy) by qPCR. AB - Consumption of milk and dairy products is considered one of the main routes of human exposure to Mycobacterium avium subsp. paratuberculosis (MAP). Quantitative data on MAP load in raw cows' milk are essential starting point for exposure assessment. Our study provides this information on a regional scale, estimating the load of MAP in bulk tank milk (BTM) produced in Emilia-Romagna region (Italy). The survey was carried out on 2934 BTM samples (88.6% of the farms herein present) using two different target sequences for qPCR (f57 and IS900). Data about the performances of both qPCRs are also reported, highlighting the superior sensitivity of IS900-qPCR. Seven hundred and eighty-nine samples tested MAP-positive (apparent prevalence 26.9%) by IS900 qPCR. However, only 90 of these samples were quantifiable by qPCR. The quantifiable samples contained a median load of 32.4 MAP cells mL(-1) (and maximum load of 1424 MAP cells mL(-1) ). This study has shown that a small proportion (3.1%) of BTM samples from Emilia-Romagna region contained MAP in excess of the limit of detection (1.5 * 10(1) MAP cells mL(-1) ), indicating low potential exposure for consumers if the milk subsequently undergoes pasteurization or if it is destined to typical hard cheese production. PMID- 26991109 TI - BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis. AB - BACKGROUND: Anti-EGFR antibody-based treatment is an important therapeutic strategy for advanced colorectal cancer (CRC); despite this, several mutations- including KRAS, BRAF, and PIK3CA mutations, and HER2 amplification--are associated with the mechanisms underlying the development of resistance to anti EGFR therapy. The aim of our study was to investigate the frequencies and clinical implications of these genetic alterations in advanced CRC. METHODS: KRAS, BRAF, and PIK3CA mutations were determined by Cobas real-time polymerase chain reaction (PCR) in 191 advanced CRC patients with distant metastasis. Microsatellite instability (MSI) status was determined by a fragmentation assay and HER2 amplification was assessed by silver in situ hybridization. In addition, KRAS mutations were investigated by the Sanger sequencing method in 97 of 191 CRC cases. RESULTS: Mutations in KRAS, BRAF, and PIK3CA were found in 104 (54.5%), 6 (3.1%), and 25 (13.1%) cases of advanced CRC, respectively. MSI-high status and HER2 amplification were observed in 3 (1.6%) and 16 (8.4%) cases, respectively. PIK3CA mutations were more frequently found in KRAS mutant type (18.3%) than KRAS wild type (6.9%) (P = 0.020). In contrast, HER2 amplifications and BRAF mutations were associated with KRAS wild type with borderline significance (P = 0.052 and 0.094, respectively). In combined analyses with KRAS, BRAF and HER2 status, BRAF mutations or HER2 amplifications were associated with the worst prognosis in the wild type KRAS group (P = 0.004). When comparing the efficacy of detection methods, the results of real time PCR analysis revealed 56 of 97 (57.7%) CRC cases with KRAS mutations, whereas Sanger sequencing revealed 49 cases (50.5%). CONCLUSIONS: KRAS mutations were found in 54.5% of advanced CRC patients. Our results support that subgrouping using PIK3CA and BRAF mutation or HER2 amplification status, in addition to KRAS mutation status, is helpful for managing advanced CRC patients. PMID- 26991111 TI - Rhodium(I) Complexes of Tridentate N-Donor Ligands and Their Supramolecular Assembly Studies. AB - New classes of tridentate N-donor rhodium(I) complexes have been synthesized and demonstrated to exhibit interesting induced self-assembly behavior by variation of external stimuli, as a result of extensive Rh(I)...Rh(I) interactions, with the assistance of pi-pi stacking and hydrophobic-hydrophobic interactions. An isodesmic aggregation mechanism has also been identified in the temperature dependent process. Upon aggregation in acetone solution, the complex molecules form wire-like nanostructures with their shape dependent on the pi-conjugation of the tridentate ligands. On the other hand, crystalline needles of rhodium(I) complexes obtained from recrystallization have also been shown to exhibit conductivity on the order of 10(-3) S cm(-1). PMID- 26991110 TI - Influence of reconstruction algorithms on image quality in SPECT myocardial perfusion imaging. AB - INTRODUCTION: We investigated if image- and diagnostic quality in SPECT MPI could be maintained despite a reduced acquisition time adding Depth Dependent Resolution Recovery (DDRR) for image reconstruction. Images were compared with filtered back projection (FBP) and iterative reconstruction using Ordered Subsets Expectation Maximization with (IRAC) and without (IRNC) attenuation correction (AC). MATERIALS AND METHODS: Stress- and rest imaging for 15 min was performed on 21 subjects with a dual head gamma camera (Infinia Hawkeye; GE Healthcare), ECG gating with 8 frames/cardiac cycle and a low-dose CT-scan. A 9 min acquisition was generated using five instead of eight gated frames and was reconstructed with DDRR, with (IRACRR) and without AC (IRNCRR) as well as with FBP. Three experienced nuclear medicine specialists visually assessed anonymized images according to eight criteria on a four point scale, three related to image quality and five to diagnostic confidence. Statistical analysis was performed using Visual Grading Regression (VGR). RESULTS: Observer confidence in statements on image quality was highest for the images that were reconstructed using DDRR (P<0.01 compared to FBP). Iterative reconstruction without DDRR was not superior to FBP. Interobserver variability was significant for statements on image quality (P<0.05) but lower in the diagnostic statements on ischemia and scar. The confidence in assessing ischemia and scar was not different between the reconstruction techniques (P = n.s.). CONCLUSION: SPECT MPI collected in 9 min, reconstructed with DDRR and AC, produced better image quality than the standard procedure. The observers expressed the highest diagnostic confidence in the DDRR reconstruction. PMID- 26991112 TI - Introducing a structured prescription form improves the quality of handwritten prescriptions in limited resource setting of developing countries. AB - INTRODUCTION: Incomplete or illegible prescriptions can lead to serious errors in administration of the prescribed medication, which can become hazardous. OBJECTIVE: Our aim is to determine if a structured prescription form can improve the quality of handwritten prescription in terms of completeness and legibility. METHODS: We conducted a prospective, non-randomized, time series study of quality of written prescriptions of general practitioners at a tertiary teaching hospital in Peshawar, Pakistan. The study involved an intervention, composed of the introduction of a pre-printed structured prescription form. The data were collected within 4 weeks including a 2-week pre-intervention phase and 2-week post-intervention phase. Completeness, quality of prescriptions and legibility were compared before and after the intervention of the pre-printed structured prescription form. RESULTS: A total of 463 prescriptions were obtained (260 in the pre-intervention phase and 203 in the post-intervention phase). Between pre intervention phase and post-intervention phase, the Pakistan Medical and Dental Council registration number presence in prescriptions improved from 73.1% to 100% (P < 0.0005). The presence of prescriber's signature improved from 92.7% to 99% (P = 0.001). Drug duration was not missing in 99.5% in post-intervention phase as compared with 90.4% in pre-intervention phase (P < 0.0005). Prescriptions with no legibility problems improved from 76.2% to 94.1% (P < 0.0005). Although not statistically significant, prescriptions in which drug dosage was not missing improved from 85% to 90.6% (P = 0.07). LIMITATIONS: We have a limited single center study. A larger study in multiple settings is needed to develop adequate evidence for such interventions. Subjective nature of prescription legibility can also be considered as a limitation. CONCLUSION: Structuring a prescription form alone may improve certain aspects of quality of written prescription in terms of completeness and legibility. PMID- 26991113 TI - To deliver or to degrade - an interplay of the ubiquitin-proteasome system, autophagy and vesicular transport in plants. AB - The efficient utilization and subsequent reuse of cell components is a key factor in determining the proper growth and functioning of all cells under both optimum and stress conditions. The process of intracellular and intercellular recycling is especially important for the appropriate control of cellular metabolism and nutrient management in immobile organisms, such as plants. Therefore, the accurate recycling of amino acids, lipids, carbohydrates or micro- and macronutrients available in the plant cell becomes a critical factor that ensures plant survival and growth. Plant cells possess two main degradation mechanisms: a ubiquitin-proteasome system and autophagy, which, as a part of an intracellular trafficking system, is based on vesicle transport. This review summarizes knowledge of both the ubiquitin-proteasome system and autophagy pathways, describes the cross-talk between the two and discusses the relationships between autophagy and the vesicular transport systems. PMID- 26991114 TI - The cytochrome bd oxidase of Escherichia coli prevents respiratory inhibition by endogenous and exogenous hydrogen sulfide. AB - When sulfur compounds are scarce or difficult to process, Escherichia coli adapts by inducing the high-level expression of sulfur-compound importers. If cystine then becomes available, the cystine is rapidly overimported and reduced, leading to a burgeoning pool of intracellular cysteine. Most of the excess cysteine is exported, but some is adventitiously degraded, with the consequent release of sulfide. Sulfide is a potent ligand of copper and heme moieties, raising the prospect that it interferes with enzymes. We observed that when cystine was provided and sulfide levels rose, E. coli became strictly dependent upon cytochrome bd oxidase for continued respiration. Inspection revealed that low micromolar levels of sulfide inhibited the proton-pumping cytochrome bo oxidase that is regarded as the primary respiratory oxidase. In the absence of the back up cytochrome bd oxidase, growth failed. Exogenous sulfide elicited the same effect. The potency of sulfide was enhanced when oxygen concentrations were low. Natural oxic-anoxic interfaces are often sulfidic, including the intestinal environment where E. coli dwells. We propose that the sulfide resistance of the cytochrome bd oxidase is a key trait that permits respiration in such habitats. PMID- 26991115 TI - Interactions between maternal killer cell immunoglobulin receptor genes and foetal HLA ligand genes contribute to type 1 diabetes susceptibility in Han Chinese. AB - In this study, we aimed to test the hypothesis that KIR haplotypes (that interact with HLA class I molecules) are associated with susceptibility in patients with T1DM in utero through maternal-foetal interaction of KIR and their HLA class I ligands in Han Chinese population. We determined the KIR genes and KIR/ligand gene combination frequencies in 59 Han Chinese children with T1D and their mothers and compared it with 159 healthy control children and their mothers. The absence of KIR-2DS1 in the mother and the presence of HLA-C2 ligand in the child were negatively associated with type 1 diabetes in the child. Our results indicate that maternal KIR genes and their interaction with foetal HLA-C2 may contribute to the risk of type 1 diabetes among Han Chinese children. PMID- 26991116 TI - Mouth breathing, another risk factor for asthma: the Nagahama Study. AB - BACKGROUND: Allergic rhinitis, a known risk factor for asthma onset, often accompanies mouth breathing. Mouth breathing may bypass the protective function of the nose and is anecdotally considered to increase asthma morbidity. However, there is no epidemiological evidence that mouth breathing is independently associated with asthma morbidity and sensitization to allergens. In this study, we aimed to clarify the association between mouth breathing and asthma morbidity and allergic/eosinophilic inflammation, while considering the effect of allergic rhinitis. METHODS: This community-based cohort study, the Nagahama Study, contained a self-reporting questionnaire on mouth breathing and medical history, blood tests, and pulmonary function testing. We enrolled 9804 general citizens of Nagahama City in the Shiga Prefecture, Japan. RESULTS: Mouth breathing was reported by 17% of the population and was independently associated with asthma morbidity. The odds ratio for asthma morbidity was 1.85 (95% CI, 1.27-2.62) and 2.20 (95% CI, 1.72-2.80) in subjects with mouth breathing alone and allergic rhinitis alone, which additively increased to 4.09 (95% CI, 3.01-5.52) when mouth breathing and allergic rhinitis coexisted. Mouth breathing in nonasthmatics was a risk for house dust mite sensitization, higher blood eosinophil counts, and lower pulmonary function after adjusting for allergic rhinitis. CONCLUSION: Mouth breathing may increase asthma morbidity, potentially through increased sensitization to inhaled allergens, which highlights the risk of mouth-bypass breathing in the 'one airway, one disease' concept. The risk of mouth breathing should be well recognized in subjects with allergic rhinitis and in the general population. PMID- 26991117 TI - Protein Science best paper awards to Tracy Clinton and Michael Thompson. PMID- 26991118 TI - Investigation of vasculature characteristics to improve venepuncture techniques in hospitalized elderly patients. AB - Targeting invisible veins might result in venepuncture complications or failure. In November 2014, we compared the diameter, depth and skin colour of invisible veins used for intravenous access with those of visible veins, aiming to provide information to improve venepuncture techniques. We measured artery depth to identify how close skin arteries were to the nearest venepuncture site. Study participants were hospitalized elderly patients. Vein diameter and vein and artery depths were measured using ultrasonic diagnostic equipment. Visualization became difficult for veins with diameters >= 2.3 mm and at depths >= 2.5 mm. The shallowest depth of arteries nearest the puncture site was 7.0 mm. Therefore, venepuncture techniques for intravenous injection should improve by targeting invisible veins with depths of 2.5 to < 7 mm in hospitalized elderly patients. PMID- 26991119 TI - Current status and future directions of T-lymphoblastic lymphoma in children and adolescents. AB - The main challenges in the treatment of T-cell lymphoblastic lymphoma (T-LBL) in children and adolescents are twofold: to increase survival rates in concert with reduction of acute and long-term toxicities including the rate of secondary malignancies. The need for molecular and prognostic markers in T-LBL is crucial to allow for systematic treatment optimization and may serve as targets for new treatment approaches. PMID- 26991120 TI - Correction: Iterative Usage of Fixed and Random Effect Models for Powerful and Efficient Genome-Wide Association Studies. PMID- 26991122 TI - Use of fibula flaps to treat persistent talonavicular nonunion: A report of three cases. AB - Owing to the limited blood supply in the midfoot, multiple arthrodesis attempts in midfood joints may result in severe osteonecrosis, leading to a difficult scenario for bone reconstruction. This article describes the use of fibula flaps (two free and one pedicled flap) to reconstruct bone defects in three cases of persistent nonunion in midfoot joints. Before admission, all patients (aged 32-56 years old) had undergone multiple arthrodesis attempts (range 3-4) aimed at treating joint diseases associated with flatfoot or Muller-Weiss syndrome. All inserted flaps were stable, and bone fusion was confirmed by X-ray examination at month 4. After the follow-up period (range 1-4 years), all patients showed normal, painless gait. No foot deformities or further complications were observed. Our report suggests that fibula flap transfer may be a good alternative for treating persistent nonunion in midfoot joints involving bone loss, and may prevent the osteonecrosis associated with limited blood supply. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:430-434, 2016. PMID- 26991121 TI - Abstracts of the 24th international isotope society (UK group) symposium: synthesis and applications of labelled compounds 2015. AB - The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Moller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK). PMID- 26991123 TI - MiRNA-Related Genetic Variations Associated with Radiotherapy-Induced Toxicities in Patients with Locally Advanced Non-Small Cell Lung Cancer. AB - Severe radiation-induced toxicities limit treatment efficacy and compromise outcomes of lung cancer. We aimed to identify microRNA-related genetic variations as biomarkers for the prediction of radiotherapy-induced acute toxicities. We genotyped 233 SNPs (161 in microRNA binding site and 72 in processing gene) and analyzed their associations with pneumonitis and esophagitis in 167 stage III NSCLC patients received definitive radiation therapy. Sixteen and 11 SNPs were associated with esophagitis and pneumonitis, respectively. After multiple comparison correction, RPS6KB2:rs10274, SMO:rs1061280, SMO:rs1061285 remained significantly associated with esophagitis, while processing gene DGCR8:rs720014, DGCR8:rs3757, DGCR8:rs1633445 remained significantly associated with pneumonitis. Patients with the AA genotype of RPS6KB2:rs10274 had an 81% reduced risk of developing esophagitis (OR: 0.19, 95% CI: 0.07-0.51, p = 0.001, q = 0.06). Patients with the AG+GG genotype of SMO:rs1061280 had an 81% reduced risk of developing esophagitis (OR: 0.19, 95% CI: 0.07-0.53, p = 0.001, q = 0.06). Patients with the GG+GA genotype of DGCR8:rs720014 had a 3.54-fold increased risk of pneumonitis (OR: 3.54, 95% CI: 1.65-7.61, p <0.05, q <0.1). Significantly cumulative effects of the top SNPs were observed for both toxicities (P-trend <0.001). Using bioinformatics tools, we found that the genotype of rs10274 was associated with altered expression of the RPS6KB2 gene. Gene-based analysis showed DGCR8 (p = 0.010) and GEMIN4 (p = 0.039) were the top genes associated with the risk of developing pneumonitis. Our results provide strong evidence that microRNA-related genetic variations contribute to the development of radiotherapy induced acute esophagitis and pneumonitis and could thus serve as biomarkers to help accurately predict radiotherapy-induced toxicity in NSCLC patients. PMID- 26991124 TI - Optimal allocation of leaf epidermal area for gas exchange. AB - A long-standing research focus in phytology has been to understand how plants allocate leaf epidermal space to stomata in order to achieve an economic balance between the plant's carbon needs and water use. Here, we present a quantitative theoretical framework to predict allometric relationships between morphological stomatal traits in relation to leaf gas exchange and the required allocation of epidermal area to stomata. Our theoretical framework was derived from first principles of diffusion and geometry based on the hypothesis that selection for higher anatomical maximum stomatal conductance (gsmax ) involves a trade-off to minimize the fraction of the epidermis that is allocated to stomata. Predicted allometric relationships between stomatal traits were tested with a comprehensive compilation of published and unpublished data on 1057 species from all major clades. In support of our theoretical framework, stomatal traits of this phylogenetically diverse sample reflect spatially optimal allometry that minimizes investment in the allocation of epidermal area when plants evolve towards higher gsmax . Our results specifically highlight that the stomatal morphology of angiosperms evolved along spatially optimal allometric relationships. We propose that the resulting wide range of viable stomatal trait combinations equips angiosperms with developmental and evolutionary flexibility in leaf gas exchange unrivalled by gymnosperms and pteridophytes. PMID- 26991125 TI - Opposing role of tumor necrosis factor receptor 1 signaling in T cell-mediated hepatitis and bacterial infection in mice. AB - Death receptor (DR) ligands such as tumor necrosis factor (TNF) have been identified as fundamental mediators of liver damage both in mouse models and in humans. While the essential site of function of DR signaling is conceivably the hepatocyte, a systematic analysis is missing. Using mice with conditional gene ablation, we analyzed the tissue-specific function of DR signaling in T cell dependent (concanavalin A) and independent (lipopolysaccharide/galactosamine) hepatitis and in models of bacterial infection (Listeria monocytogenes, lipopolysaccharide). We report that lipopolysaccharide/galactosamine-induced liver injury depends on hepatocyte-intrinsic TNF receptor 1 (p55, TNFR1). In contrast, we show that T cell-induced hepatitis was independent of TNFR1 signaling in hepatocytes, T cells, or endothelial cells. Moreover, T cell-induced hepatitis was independent of hepatocyte-intrinsic Fas-associated protein with death domain, TNF-related apoptosis-inducing ligand receptor, or Fas signaling. Instead, concanavalin A-induced hepatitis was completely prevented in mice with myeloid-derived cell (MDC)-specific deletion of TNFR1. Significantly, however, mice lacking TNFR1 in MDCs succumbed to listeria infection, although they displayed similar sensitivity toward endotoxin-induced septic shock when compared to control mice. These results suggest that TNFR1 signaling in MDCs is a critical mediator of both the detrimental and the protective functions of TNF in T cell induced hepatitis and bacterial infection, respectively. CONCLUSION: The critical site of action of DRs is completely dependent on the nature of hepatitis; the data specify MDCs as the essential cell type of TNFR1 function in T cell-mediated hepatitis and in the response to listeria, thereby identifying the opposing role of MDC TNFR1 in autoimmunity and bacterial infection. (Hepatology 2016;64:508 521). PMID- 26991126 TI - Focus on Teen Men: Evaluating the Effectiveness of the Wise Guys Program. AB - PROBLEM: Many interventions designed to promote safe sexual behaviors in teens focus on young women. Wise Guys is one curricular intervention designed to foster safe sexual practices in young men. This study assessed knowledge, attitude, and behavioral changes as the result of Wise Guys. METHODS: This pre/posttest descriptive study measured changes in knowledge, attitudes, and sexual behaviors in 159 young men. FINDINGS: This study detected limited knowledge and attitude changes but yielded statistically significant differences in safe sexual behaviors and likelihood to talk with parents or guardians about sexuality and dating. CONCLUSIONS: This study revealed important benefits of Wise Guys and proposed future mixed methods research to ensure that authentic teen voices inform programming. Nurses working with adolescents may find this information valuable as they address sexual health issues in their work. PMID- 26991127 TI - Correlation of Early Recurrence With In Vitro Adenosine Triphosphate Based Chemotherapy Response Assay in Pancreas Cancer With Postoperative Gemcitabine Chemotherapy. AB - INTRODUCTION: Gemcitabine-based regimens represent the standard systemic first line treatment in patients after pancreatic resection. However, the clinical impact of gemcitabine varies significantly in individuals because of chemoresistance. An in vitro adenosine triphosphate based chemotherapy response assay (ATP-CRA) was designed to evaluate the sensitivity of cancer cells to various chemotherapeutic agents. This study investigated the correlation between in vitro gemcitabine sensitivity of tumor cells and early recurrence after curative resection. METHOD: From January 2007 to December 2010, the ATP-CRA for gemcitabine was tested in 64 patients surgically treated for pancreas cancer at Gangnam Severance Hospital, Seoul, Korea. We analyzed the relationship between chemosensitivity and early systemic recurrence in patients with pancreas cancer to predict disease-free survival (DFS) after curative resection in pancreas cancer. RESULT: The mean cell death rate (CDR) was 20.0 (+/-14.5) and divided into two groups according to the mean values of the CDR. Lymphovascular invasion was more frequently shown in gemcitabine resistance group without statistical significance. In univariate and multivariate analysis, advanced tumor stage and gemcitabine sensitive group (CDR >= 20) were identified as independent prognostic factors for DFS. CONCLUSIONS: Gemcitabine sensitivity measured by ATP-CRA was well correlated with in vivo drug responsibility to predict early recurrence following gemcitabine-based adjuvant chemotherapy in patients with pancreas cancer. PMID- 26991128 TI - Arabidopsis lipoxygenase 2 is essential for formation of green leaf volatiles and five-carbon volatiles. AB - Plants biosynthesize a variety of bioactive lipid derivatives, such as green leaf volatiles (GLVs) and jasmonates (JAs). Here we identify a lipoxygenase 2 (LOX2) involved in GLV biosynthesis in Arabidopsis using mutant lines for each of the six LOX isoforms present in Arabidopsis. We found that formation of five carbon volatiles was also dependent on LOX2. LOX2 is known to be involved in formation of JA; thus, LOX2 is apparently versatile in function. The results in this study suggested that LOX2 activity is suppressed in intact cells but activated upon tissue damage to support the rapid GLV-burst observed in wounded leaves. PMID- 26991129 TI - Unmasking the linear behaviour of slow motor adaptation to prolonged convergence. AB - Adaptation to changing environmental demands is central to maintaining optimal motor system function. Current theories suggest that adaptation in both the skeletal-motor and oculomotor systems involves a combination of fast (reflexive) and slow (recalibration) mechanisms. Here we used the oculomotor vergence system as a model to investigate the mechanisms underlying slow motor adaptation. Unlike reaching with the upper limbs, vergence is less susceptible to changes in cognitive strategy that can affect the behaviour of motor adaptation. We tested the hypothesis that mechanisms of slow motor adaptation reflect early neural processing by assessing the linearity of adaptive responses over a large range of stimuli. Using varied disparity stimuli in conflict with accommodation, the slow adaptation of tonic vergence was found to exhibit a linear response whereby the rate (R(2) = 0.85, P < 0.0001) and amplitude (R(2) = 0.65, P < 0.0001) of the adaptive effects increased proportionally with stimulus amplitude. These results suggest that this slow adaptive mechanism is an early neural process, implying a fundamental physiological nature that is potentially dominated by subcortical and cerebellar substrates. PMID- 26991132 TI - A General and Selective Rhodium-Catalyzed Reduction of Amides, N-Acyl Amino Esters, and Dipeptides Using Phenylsilane. AB - This article describes a selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)]. The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties. PMID- 26991130 TI - Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice. AB - The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe2 O3 -NPs) could be toxic to mice testis. Fe2 O3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe2 O3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe2 O3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe2 O3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe2 O3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe2 O3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe2 O3 -NPs exposure may be associated with Fe2 O3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe2 O3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe2 O3 -NPs. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017. PMID- 26991131 TI - Evolution and perspectives of cultivar identification and traceability from tree to oil and table olives by means of DNA markers. AB - In recent years, an increasing number of typicality marks has been awarded to high-quality olive oils produced from local cultivars. In this case, quality control requires effective varietal checks of the starting materials. Moreover, accurate cultivar identification is essential in vegetative-propagated plants distributed by nurseries and is a pre-requisite to register new cultivars. Food genomics provides many tools for cultivar identification and traceability from tree to oil and table olives. The results of the application of different classes of DNA markers to olive with the purpose of checking cultivar identity and variability of plant material are extensively discussed in this review, with special regard to repeatability issues and polymorphism degree. The characterization of olive germplasm from all countries of the Mediterranean basin and from less studied geographical areas is described and innovative high throughput molecular tools to manage reference collections are reviewed. Then the transferability of DNA markers to processed products - virgin olive oils and table olives - is overviewed to point out strengths and weaknesses, with special regard to (i) the influence of processing steps and storage time on the quantity and quality of residual DNA, (ii) recent advances to overcome the bottleneck of DNA extraction from processed products, (iii) factors affecting whole comparability of DNA profiles between fresh plant materials and end-products, (iv) drawbacks in the analysis of multi-cultivar versus single-cultivar end products and (v) the potential of quantitative polymerase chain reaction (PCR) based techniques. (c) 2016 Society of Chemical Industry. PMID- 26991133 TI - Copper/Guanidine-Catalyzed Asymmetric Alkynylation of Isatins. AB - The highly enantioselective alkynylation of isatins, catalyzed by a bifunctional guanidine/CuI catalyst under mild reaction conditions, is described. The reaction is broad in scope with respect to alkyl/aryl-substituted terminal alkynes and substituted isatins, thus affording bioactive propargylic alcohols in excellent yields and enantioselectivities. PMID- 26991134 TI - The multidisciplinary team. PMID- 26991135 TI - Combating antibiotic resistance, mitigating future threats and ongoing initiatives. AB - AIMS AND OBJECTIVES: To emphasise the impact of antibiotic resistance as a persistent, global health threat and highlight efforts to improve this complex problem. BACKGROUND: Political agendas, legislation, development of therapies and educational initiatives are essential to mitigate the increasing rate of antibiotic resistance. DESIGN: Original manuscript. RESULTS: Prescribers, policymakers and researchers are charged with the complex task of mitigating antibiotic resistance in an era when new treatments for bacterial infections are limited. CONCLUSIONS: Monitoring, surveillance and incentivising of practice, policy and new treatments provide solutions to antibiotic resistance in both the human and agricultural sectors. RELEVANCE TO CLINICAL PRACTICE: This article emphasises the complexity of antibiotic resistance and highlights the need for a multifaceted approach to improve health care outcomes. PMID- 26991136 TI - beta-asarone and levodopa co-administration increase striatal dopamine level in 6 hydroxydopamine induced rats by modulating P-glycoprotein and tight junction proteins at the blood-brain barrier and promoting levodopa into the brain. AB - Levodopa (L-dopa) is widely considered as one of the most effective drug constituents in the treatment of Parkinson's disease (PD), but the blood-brain barrier (BBB) permeability of L-dopa is <5%, which causes low efficacy. Neuroprotective effects of beta-asarone on 6-hydroxydopamine (6-OHDA)-induced PD rats were demonstrated by our previous studies. Co-administration of beta-asarone and L-dopa has not been explored until being investigated on PD rats in this study. PD rats were divided into four groups: untreated, L-dopa-treated, beta asarone-treated and co-administered-treated groups. All of the treatments were administered to the rats twice per day for 30 days. The L-dopa, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), S100beta and neuron-specific enolase (NSE) levels were subsequently determined. The P glycoprotein (P-gp), zonula occludens-1 (ZO-1), claudin-5, occludin and actin expression was also assessed in cortex. Changes in BBB ultrastructure were observed using transmission electron microscopy. Our results showed that the co administered treatment increased levels of L-dopa, DA, DOPAC and HVA in striatum, and S100beta in plasma, but down-regulated NSE, P-gp, ZO-1, occludin, actin and claudin-5 in cortex. Crevices were observed between capillary endothelial cells at intercellular tight junction of the striatum in co-administered-treated group, while the endothelial cells in untreated group were tightly jointing each other. In addition, the correlations of L-dopa or DA and P-gp or tight junction proteins respectively were significantly negative in co-administered- and beta-asarone treated groups. These findings suggest that co-administered treatment may enhance the L-dopa BBB permeability and attenuate brain injury, which may be beneficial to PD treatment. PMID- 26991137 TI - In vitro analysis of biopolymer coating with glycidoxypropyltrimethoxysilane on hernia meshes. AB - Certain coatings may improve the biocompatibility of hernia meshes. The coating with self-assembled monolayers, such as glycidoxypropyltrimethoxysilane (GOPS) can also improve the materials characteristics of implants. This approach was not yet explored in hernia meshes. It was the aim of this work to clarify if and how hernia meshes with their three-dimensional structure can be coated with GOPS and with which technique this coating can be best characterized. Commercially available meshes made from polypropylene (PP), polyester (PE), and expanded polytetrafluorethylene (ePTFE) have been coated with GOPS. The coatings were analyzed via X-ray photoelectron spectroscopy (XPS), confocal laser scanning microscopy (CLSM), and cell proliferation test (mouse fibroblasts). Cell viability and cytotoxicity were tested by MTT test. With the GOPS surface modification, the adherence of mouse fibroblasts on polyester meshes and the proliferation on ePTFE meshes were increased compared to noncoated meshes. Both XPS and CLSM are limited in their applicability and validity due to the three dimensional mesh structure while CLSM was overall more suitable. In the MTT test, no negative effects of the GOPS coating on the cells were detected after 24 h. The present results show that GOPS coating of hernia meshes is feasible and effective. GOPS coating can be achieved in a fast and cost-efficient way. Further investigations are necessary with respect to coating quality and adverse effects before such a coating may be used in the clinical routine. In conclusion, GOPS is a promising material that warrants further research as coating of medical implants. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1083-1090, 2017. PMID- 26991138 TI - Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study. AB - To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 MUg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P < 0.001). Both drugs caused a significant rise in number of platelets on the 7th and the 14th day of treatment. Compared to IVIG, except a significant drop in hemoglobin concentration (P < 0.001), anti-D had lower rate of side effects including fever (P < 0.05), allergy (P < 0.01), and headache (P < 0.001). Our results showed that anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. PMID- 26991139 TI - Quantification and semiquantification of multiple representative components for the holistic quality control of Allii Macrostemonis Bulbus by ultra high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry. AB - Allii Macrostemonis Bulbus (named Xiebai in China) is a folk medicine with medicinal values for the treatment of thoracic obstruction and cardialgia, and a food additive as well. However, there is even no quantitative standard for Allii Macrostemonis Bulbus recorded in the current edition of the Chinese Pharmacopeia. Hence, simultaneous assay of multiple components is urgent. In this study, chemometric methods were firstly applied to discover the components with significant fluctuation among multiple Allii Macrostemonis Bulbus samples based on optimized fingerprints. Meanwhile, the major components and main absorbed components in rats were all selected as its representative components. Subsequently, a sensitive method was established for the simultaneous determination of 54 components (15 components for quantification and 39 components for semiquantification) by ultra high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Moreover, the validated method was successfully applied to evaluate the quality of multiple samples on the market. It became known that multiple Allii Macrostemonis Bulbus samples varied significantly and showed poor consistency. This work illustrated that the proposed approach could improve the quality of Allii Macrostemonis Bulbus, and it also provided a feasible method for quality evaluation of other traditional Chinese medicines. PMID- 26991140 TI - Correlating HIV tropism with immunological response under combination antiretroviral therapy. AB - OBJECTIVES: A significant percentage of patients infected with HIV-1 experience only suboptimal CD4 cell recovery while treated with combination therapy (cART). It is still unclear whether viral properties such as cell tropism play a major role in this incomplete immune response. This study therefore intended to follow the tropism evolution of the HIV-1 envelope during periods of suppressive cART. METHODS: Viruses from two distinct patient groups, one with good and another one with poor CD4 recovery after 5 years of suppressive cART, were genotypically analysed for viral tropism at baseline and at the end of the study period. RESULTS: Patients with CCR5-tropic CC-motif chemokine receptor 5 viruses at baseline tended to maintain this tropism to the study end. Patients who had a CXCR4-tropic CXC-motif chemokine receptor 4 virus at baseline were overrepresented in the poor CD4 recovery group. Overall, however, the majority of patients presented with CCR5-tropic viruses at follow-up. CONCLUSIONS: Our data lend support to the hypothesis that tropism determination can be used as a parameter for disease progression even if analysed long before the establishment of a poorer immune response. Moreover, the lasting predominating CCR5-tropism during periods of full viral control suggests the involvement of cellular mechanisms that preferentially reduce CXCR4-tropic viruses during cART. PMID- 26991142 TI - Nationwide Cross-Sectional Study on Bovine Tuberculosis by Intra Vitam Testing in Germany, 2013-2014. AB - Germany was declared officially free from bovine tuberculosis (bTB) effective from 1 July 1996. After the occurrence of several Mycobacterium (M.) bovis outbreaks in north-western Germany in recent years with high intraherd prevalence at the time of detection, the reliability of abattoir surveillance as the principal component of the national bTB control programme was debated by veterinary public health officials. Rising numbers of wildlife-associated outbreaks caused by M. caprae in southern Germany eventually prompted a nationwide cross-sectional study on bTB. A total of 51 999 cattle, that is 0.41% of the national herd kept on 1.73% of German cattle farms, were tested. Despite 4 positive and 152 inconclusive single intradermal comparative cervical test results, none of the animals was confirmed as bTB-positive by a subsequent interferon-release assay or by post-mortem PCR testing. The estimated prevalence of bTB in Germany was thus calculated as 0.0% (CI 0.0000-0.0064%) affirming that Germany still qualifies as an officially tuberculosis-free (OTF) country. Occasional randomized nationwide testing can be an appropriate tool to reassure the OTF status and may also help to maintain an appropriate training level for the diagnostic procedures and for supporting sustained disease awareness among stakeholders. PMID- 26991143 TI - Nodular fasciitis of the vulva: a challenging histopathologic diagnosis supported by the detection of USP6 gene rearrangement. AB - Nodular fasciitis involving the vulva on physical examination can mimic a Bartholin gland lesion, and histologically can have overlapping features with more ominous mesenchymal pathologies. We describe a case in which a 52-year-old perimenopausal woman presents with a vulvar mass. After an initial biopsy and later excision, the myofibroblastic lesion was noted to have areas of differing cellularity, with compact nodule formations at the periphery. Immunohistochemical staining showed lesional cells to be positive for desmin, estrogen receptor, progesterone receptor, and smooth muscle actin, and negative for CD34, ALK-1, myogenin, caldesmon, S100, and wide spectrum (Oscar) cytokeratin. Desmin is generally negative in this lesion type, but the positivity in this case was considered to be secondary to the origin of the myofibroblastic cells of the vulva. The morphologic pattern and immunophenotype favored a diagnosis of nodular fasciitis, however, the degree of hypercellularity and desmin positivity warranted further analysis. The diagnosis was supported with fluorescence in situ hybridization that demonstrated USP6 gene rearrangement. This highlights the necessity in certain challenging cases for ancillary molecular and/or cytogenetic analysis. PMID- 26991141 TI - Winner of the Young Investigator Award of the Society for Biomaterials at the 10th World Biomaterials Congress, May 17-22, 2016, Montreal QC, Canada: Microribbon-based hydrogels accelerate stem cell-based bone regeneration in a mouse critical-size cranial defect model. AB - Stem cell-based therapies hold great promise for enhancing tissue regeneration. However, the majority of cells die shortly after transplantation, which greatly diminishes the efficacy of stem cell-based therapies. Poor cell engraftment and survival remain a major bottleneck to fully exploiting the power of stem cells for regenerative medicine. Biomaterials such as hydrogels can serve as artificial matrices to protect cells during delivery and guide desirable cell fates. However, conventional hydrogels often lack macroporosity, which restricts cell proliferation and delays matrix deposition. Here we report the use of injectable, macroporous microribbon (MURB) hydrogels as stem cell carriers for bone repair, which supports direct cell encapsulation into a macroporous scaffold with rapid spreading. When transplanted in a critical-sized, mouse cranial defect model, MURB-based hydrogels significantly enhanced the survival of transplanted adipose derived stromal cells (ADSCs) (81%) and enabled up to three-fold cell proliferation after 7 days. In contrast, conventional hydrogels only led to 27% cell survival, which continued to decrease over time. MicroCT imaging showed MURBs enhanced and accelerated mineralized bone repair compared to hydrogels (61% vs. 34% by week 6), and stem cells were required for bone repair to occur. These results suggest that paracrine signaling of transplanted stem cells are responsible for the observed bone repair, and enhancing cell survival and proliferation using MURBs further promoted the paracrine-signaling effects of ADSCs for stimulating endogenous bone repair. We envision MURB-based scaffolds can be broadly useful as a novel scaffold for enhancing stem cell survival and regeneration of other tissue types. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1321-1331, 2016. PMID- 26991144 TI - Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 9q22.33 and 14q13.3 detects novel candidate functional SNPs in Europeans from metropolitan France and Melanesians from New Caledonia. AB - Incidence of differentiated thyroid carcinoma varies considerably between countries and ethnic groups, with particularly high incidence rates in Melanesians of New Caledonia. Differentiated thyroid cancer (DTC) has a familial relative risk higher than other cancers, highlighting the contribution of inherited factors to the disease. Recently, genome-wide association studies (GWAS) identified several DTC susceptibility loci. The most robust associations were reported at loci 9q22 (rs965513 and rs1867277) and 14q13 (rs944289 and rs116909734). In this study, we performed a fine-mapping study of the two gene regions among Europeans and Melanesians from Metropolitan France and New Caledonia. We examined 81 single nucleotide polymorphisms (SNPs) at 9q22 and 561 SNPs at 14q13 in Europeans (625 cases/776 controls) and in Melanesians (244 cases/189 controls). The association with the four SNPs previously identified in GWAS was replicated in Europeans while only rs944289 was replicated in Melanesians. Among Europeans, we found that the two SNPs previously reported at 9q22 were not independently associated to DTC and that rs965513 was the predominant signal; at 14q13, we showed that the haplotype rs944289[C] rs116909374[C]-rs999460[T] was significantly associated with DTC risk and that the association with rs116909374 differed by smoking status (p-interaction = 0.03). Among Melanesians, a new independent signal was observed at 14q13 for rs1755774 which is strongly correlated to rs2787423; this latter is potentially a functional variant. Significant interactions with parity (p < 0.05) and body mass index were observed for rs1755774 and rs2787423. This study contributed to a better characterization of the DTC loci 9q22 and 14q13 in Europeans and in Melanesians and has identified novel variants to be prioritized for further functional studies. PMID- 26991145 TI - High rate of mortality in Spanish community-dwelling population aged 85 with atrial fibrillation after three years of follow-up: The Octabaix study. AB - AIM: To assess the possible association between three-year global mortality and atrial fibrillation (AF) in 328 community-dwelling participants aged 85 at baseline. METHODS: Sociodemographic data, comorbidity and geriatric assessment tools, thromboembolic risk, and AF therapy were assessed. We compared the patients who survived with those who died. RESULTS: At baseline, 41 (12.5%) of participants had permanent AF, and 13 of them died (31.7%) after the three-year follow-up period compared with 44 (15.3%) of the rest of cohort (P = 0.01). Cox regression analysis identified two significant clinical variables as independent predictors of three-year risk of global mortality: Lawton Index (hazard ratio 0.82, 95% confidence interval 0.75-0.91) and AF (hazard ratio 1.90, 95% confidence interval 1.01-3.56). None of the other of variables evaluated showed predictive value of global mortality in the AF patients. CONCLUSION: In oldest old community-dwelling participants, AF is an independent risk factor for global mortality after a three-year follow-up period. PMID- 26991146 TI - A novel method of comparing mating success and survival reveals similar sexual and viability selection for mobility traits in female tree crickets. AB - The relationship between sexual and viability selection in females is necessarily different than that in males, as investment in sexual traits potentially comes at the expense of both fecundity and survival. Accordingly, females do not usually invest in sexually selected traits. However, direct benefits obtained from mating, such as nuptial gifts, may encourage competition among females and subsidize investment into sexually selected traits. We compared sexual and viability selection on female tree crickets Oecanthus nigricornis, a species where females mate frequently to obtain nuptial gifts and sexual selection on females is likely. If male choice determines female mating success in this species, we expect sexual selection for fecundity traits, as males of many species prefer more fecund females. Alternatively, intrasexual scramble or combat competition on females may select for larger jumping legs or wider heads (respectively). We estimated mating success in wild caught crickets using microsatellite analysis of stored sperm and estimated relative viability by comparing surviving female O. nigricornis to those captured by a common wasp predator. In support of the scramble competition hypothesis, we found sexual selection for females with larger hind legs and narrower heads. We also found stabilizing viability selection for intermediate head width and hind leg size. As predicted, traits under viability and sexual selection were very similar, and the direction of that selection was not opposing. However, because the shape of sexual and viability selection differs, these episodes of selection may favour slightly different trait sizes. PMID- 26991148 TI - Statistics Commentary Series: Commentary #14--Confidence Intervals. PMID- 26991147 TI - Heart Rate Recovery and Systolic Blood Pressure Recovery After Maximal Exercise in Prevalent Users of Stimulant Medications. PMID- 26991149 TI - Simultaneous inference on treatment effects in survival studies with factorial designs. AB - A clinical trial with a 2*2 factorial design involves randomization of subjects to treatment A or A? and, within each group, further randomization to treatment B or B?. Under this design, one can assess the effects of treatments A and B on a clinical endpoint using all patients. One may additionally compare treatment A, treatment B, or combination therapy AB to A?B?. With multiple comparisons, however, it may be desirable to control the overall type I error, especially for regulatory purposes. Because the subjects overlap in the comparisons, the test statistics are generally correlated. By accounting for the correlations, one can achieve higher statistical power compared to the conventional Bonferroni correction. Herein, we derive the correlation between any two (stratified or unstratified) log-rank statistics for a 2*2 factorial design with a survival time endpoint, such that the overall type I error for multiple treatment comparisons can be properly controlled. In addition, we allow for adjustment of prognostic factors in the treatment comparisons and conduct simultaneous inference on the effect sizes. We use simulation studies to show that the proposed methods perform well in realistic situations. We then provide an application to a recently completed randomized controlled clinical trial on alcohol dependence. Finally, we discuss extensions of our approach to other factorial designs and multiple endpoints. PMID- 26991150 TI - Is the diagnostic coding position of acute heart failure related to mortality? A report from the Euro Heart Failure Survey-1. AB - AIMS: Most studies on acute heart failure (HF) exploring the relationship between admissions to hospital for HF and subsequent outcomes have focused only on HF coded as the primary diagnosis, but many other patients have admissions complicated by HF requiring attention. Failure to quantify the total hospital burden of HF underestimates its health economic impact, leading to underprovision of resources for its care. METHODS AND RESULTS: The First Euro Heart Failure Survey (EHFS-1) screened consecutive deaths and discharges, regardless of cause, from medical wards in 115 hospitals from 24 European countries during 2000-2001, to identify patients with known or suspected HF. Information on presenting symptoms and signs were gathered. Of 10 701 patients enrolled, HF was reported as the primary reason for admission in 4234 (40%), a secondary reason for admission if it complicated or prolonged stay in 1772 (17%), and in 4695 (43%) patients it was uncertain whether HF was actively contributing to the admission. Mortality on the index admission was 301 (7%), 290 (16%), and 189 (4%), respectively, with hazard ratios of 1.73 (P < 0.001) and 3.26 (P < 0.001) compared with the 'uncertain' group. In the 12 weeks following discharge, 287 (7%) patients with a primary, 117 (8%) with a secondary, and 238 (5%) with an incidental or uncertain diagnosis of HF died. CONCLUSION: Patients admitted to hospital with HF as a secondary rather than a primary diagnosis have a high mortality. More attention should be focused on patients with a secondary diagnosis of HF in terms of both care and research. PMID- 26991152 TI - Genome-wide association mapping of heritable temperament variation in the Tennessee Walking Horse. AB - Temperament is a key criterion in the selection of horses for both leisure and competitive riding to ensure optimal performance and safety. The Tennessee Walking Horse (TWH) is described as a calm, docile breed and is often used as a trail, show and pleasure horse. However, among horse owners and caretakers, there are anecdotes supporting familial and disciplinal typical behaviors and personalities. To investigate the contribution of genetics to temperament, we collected a behavior questionnaire, brief training history and identifying information for 276 TWH, as well as blood or hair samples for DNA. Factor analysis was conducted on the 20-item questionnaire for the set of 216 horses that met inclusion thresholds. Factor analysis identified four temperament factors in TWH: 'anxious', 'tractable', 'agonistic' and 'gregarious'. These four factors account for 64% of the total trait variance. DNA from 113 TWHs were selected and genotyped using the Equine SNP70 bead chip for three separate genome wide association studies (GWAs) using the factor 1-anxious, factor 2-tractable and factor 3-agonistic scores as the phenotype. Quantitative association analysis identified significant candidate loci for each factor that warrant further investigation. PMID- 26991151 TI - Predictors of prevalent statin use among older adults identified as statin initiators based on Medicare claims data. AB - PURPOSE: Few studies have evaluated the degree to which prescription drug initiators are correctly identified using claims data. We examine the prevalence and predictors of recent statin possession in statin initiators identified using claims data. METHODS: Among Medicare Current Beneficiary Survey (MCBS) respondents, we used Medicare Part D claims from 2006 to 2011 to identify statin initiators using a 12-month baseline period of no prior statin claims. Using MCBS interview data, we identified those with self-reported statins obtained during the baseline period. We used log-binomial regression to estimate adjusted prevalence ratios (adjPR) and 95% confidence intervals (CI) for predictors of recent statin possession. RESULTS: Among 766 statin initiators identified in prescription claims, 155 (20%) reported recent statin possession during baseline. Beneficiaries with no Part D claims in the past 30 days (adjPR = 1.49, 95%CI: 1.13, 1.96), those with no inpatient, outpatient or physician visits in the past 30 days (adjPR = 1.50, 95%CI: 1.11, 2.03), those with a brand name statin index claim (adjPR = 1.55, 95%CI: 1.19, 2.02), and those with an index claim in January or February (adjPR = 1.50, 95%CI: 1.00, 2.26) had an increased probability of recent statin possession. CONCLUSIONS: In a cohort of statin initiators identified using prescription claims, 20% had evidence of statin possession during the baseline period. Pharmacoepidemiologic new user studies may benefit from including sensitivity analyses within subgroups less likely to include prevalent users to assess the robustness of key findings to misidentification of the time of treatment initiation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991153 TI - Bowel endometriosis: an unusual cause of rectal bleeding. PMID- 26991154 TI - Metabolomic profiling reveals differential effects of glucagon-like peptide-1 and insulin on nutrient partitioning in ovine liver. AB - This study was conducted to identify the insulin-independent actions of glucagon like peptide-1 (GLP-1 (7-36 amide)) in partitioning nutrient metabolism in ovine liver. Four Suffolk wethers (60.0 +/- 6.7 kg body weight (BW)) were used in a repeated-measure design under euglycemic--hyperinsulinemic and hyper -GLP-1 clamps for 150 min with intravenous infusion of insulin (0.5 mU/kg BW/min; from 0 to 90 min), GLP-1 (0.5 ug/kg BW/min; from 60 to 150 min) and both hormones co administered from 60 to 90 min. Liver biopsies were collected at 0, 60, 90 and 150 min to represent the metabolomic profiling of baseline, insulin, insulin plus GLP-1, and GLP-1, respectively, and were analyzed for metabolites using Capillary Electrophoresis Time-of-Flight Mass Spectrometer. Metabolomics analysis reveals 51 metabolites as being significantly altered (P < 0.05) by insulin and GLP-1 infusion compared to baseline values. Insulin infusion enhanced glycolysis, lipogenesis, oxidative stress defense and cell proliferation pathways, but reduced protein breakdown, gluconeogenesis and ketogenesis pathways. Conversely, GLP-1 infusion promoted lipolytic and ketogenic pathways accompanied by a lowered lipid clearance from the liver as well as elevated oxidative stress defense and nucleotide degradation. Despite further research still being warranted, our data suggest that GLP-1 may exert insulin-antagonistic effects on hepatic lipid and nucleotide metabolism in ruminants. PMID- 26991155 TI - Rapid Diversification of BetI-Based Transcriptional Switches for the Control of Biosynthetic Pathways and Genetic Circuits. AB - Synthetic biologists are in need of genetic switches, or inducible sensor/promoter systems, that can be reliably integrated in multiple contexts. Using a liquid-based selection method, we systematically engineered the choline inducible transcription factor BetI, yielding various choline-inducible and choline-repressive promoter systems with various input-output characteristics. In addition to having high stringency and a high maximum induction level, they underwent a graded and single-peaked response to choline. Taking advantage of these features, we demonstrated the utility of these systems for controlling the carotenoid biosynthetic pathway and for constructing two-input logic gates. Additionally, we demonstrated the rapidity, throughput, robustness, and cost effectiveness of our selection method, which facilitates the conversion of natural genetic controlling systems into systems that are designed for various synthetic biology applications. PMID- 26991156 TI - The neural networks of subjectively evaluated emotional conflicts. AB - Previous work on the neural underpinnings of emotional conflict processing has largely focused on designs that instruct participants to ignore a distracter which conflicts with a target. In contrast, this study investigated the noninstructed experience and evaluation of an emotional conflict, where positive or negative cues can be subjectively prioritized. To this end, healthy participants freely watched short film scenes that evoked emotional conflicts while their BOLD responses were measured. Participants' individual ratings of conflict and valence perception during the film scenes were collected immediately afterwards, and the individual ratings were regressed against the BOLD data. Our analyses revealed that (a) amygdala and medial prefrontal cortex were significantly involved in prioritizing positive or negative cues, but not in subjective evaluations of conflict per se, and (b) superior temporal sulcus (STS) and inferior parietal lobule (IPL), which have been implicated in social cognition and emotion control, were involved in both prioritizing positive or negative cues and subjectively evaluating conflict, and may thus constitute "hubs" or "switches" in emotional conflict processing. Psychophysiological interaction (PPI) analyses further revealed stronger functional connectivity between IPL and ventral prefrontal-medial parietal areas in prioritizing negative cues, and stronger connectivity between STS and dorsal-rostral prefrontal-medial parietal areas in prioritizing positive cues. In sum, our results suggest that IPL and STS are important in the subjective evaluation of complex conflicts and influence valence prioritization via prefrontal and parietal control centers. Hum Brain Mapp 37:2234-2246, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991157 TI - Realization of the Contextuality-Nonlocality Tradeoff with a Qubit-Qutrit Photon Pair. AB - We report our experimental results on the no-disturbance principle, which imposes a fundamental monogamy relation on contextuality versus nonlocality. We employ a photonic qutrit-qubit hybrid to explore no-disturbance monogamy at the quantum boundary spanned by noncontextuality and locality inequalities. In particular, we realize the single point where the quantum boundary meets the no-disturbance boundary. Our results agree with quantum theory and satisfy the stringent monogamy relation thereby providing direct experimental evidence of a tradeoff between locally contextual correlations and spatially separated correlations. Thus, our experiment provides evidence that entanglement is a particular manifestation of a more fundamental quantum resource. PMID- 26991158 TI - Upper Bounds on Spontaneous Wave-Function Collapse Models Using Millikelvin Cooled Nanocantilevers. AB - Collapse models predict a tiny violation of energy conservation, as a consequence of the spontaneous collapse of the wave function. This property allows us to set experimental bounds on their parameters. We consider an ultrasoft magnetically tipped nanocantilever cooled to millikelvin temperature. The thermal noise of the cantilever fundamental mode has been accurately estimated in the range 0.03-1 K, and any other excess noise is found to be negligible within the experimental uncertainty. From the measured data and the cantilever geometry, we estimate the upper bound on the continuous spontaneous localization collapse rate in a wide range of the correlation length r_{C}. Our upper bound improves significantly previous constraints for r_{C}>10^{-6} m, and partially excludes the enhanced collapse rate suggested by Adler. We discuss future improvements. PMID- 26991159 TI - Steering Maps and Their Application to Dimension-Bounded Steering. AB - The existence of quantum correlations that allow one party to steer the quantum state of another party is a counterintuitive quantum effect that was described at the beginning of the past century. Steering occurs if entanglement can be proven even though the description of the measurements on one party is not known, while the other side is characterized. We introduce the concept of steering maps, which allow us to unlock sophisticated techniques that were developed in regular entanglement detection and to use them for certifying steerability. As an application, we show that this allows us to go beyond even the canonical steering scenario; it enables a generalized dimension-bounded steering where one only assumes the Hilbert space dimension on the characterized side, with no description of the measurements. Surprisingly, this does not weaken the detection strength of very symmetric scenarios that have recently been carried out in experiments. PMID- 26991160 TI - Minimal noise subsystems. AB - A system subjected to noise contains a decoherence-free subspace or subsystem (DFS) only if the noise possesses an exact symmetry. Here we consider noise models in which a perturbation breaks a symmetry of the noise, so that if S is a DFS under a given noise process it is no longer so under the new perturbed noise process. We ask whether there is a subspace or subsystem that is more robust to the perturbed noise than S. To answer this question we develop a numerical method that allows us to search for subspaces or subsystems that are maximally robust to arbitrary noise processes. We apply this method to a number of examples, and find that a subsystem that is a DFS is often not the subsystem that experiences minimal noise when the symmetry of the noise is broken by a perturbation. We discuss which classes of noise have this property. PMID- 26991161 TI - Automated Search for new Quantum Experiments. AB - Quantum mechanics predicts a number of, at first sight, counterintuitive phenomena. It therefore remains a question whether our intuition is the best way to find new experiments. Here, we report the development of the computer algorithm Melvin which is able to find new experimental implementations for the creation and manipulation of complex quantum states. Indeed, the discovered experiments extensively use unfamiliar and asymmetric techniques which are challenging to understand intuitively. The results range from the first implementation of a high-dimensional Greenberger-Horne-Zeilinger state, to a vast variety of experiments for asymmetrically entangled quantum states-a feature that can only exist when both the number of involved parties and dimensions is larger than 2. Additionally, new types of high-dimensional transformations are found that perform cyclic operations. Melvin autonomously learns from solutions for simpler systems, which significantly speeds up the discovery rate of more complex experiments. The ability to automate the design of a quantum experiment can be applied to many quantum systems and allows the physical realization of quantum states previously thought of only on paper. PMID- 26991162 TI - Critical Schwinger Pair Production. AB - We investigate Schwinger pair production in spatially inhomogeneous electric backgrounds. A critical point for the onset of pair production can be approached by fields that marginally provide sufficient electrostatic energy for an off shell long-range electron-positron fluctuation to become a real pair. Close to this critical point, we observe features of universality which are analogous to continuous phase transitions in critical phenomena with the pair-production rate serving as an order parameter: electric backgrounds can be subdivided into universality classes and the onset of pair production exhibits characteristic scaling laws. An appropriate design of the electric background field can interpolate between power-law scaling, essential Berezinskii-Kosterlitz-Thouless type scaling, and a power-law scaling with log corrections. The corresponding critical exponents only depend on the large-scale features of the electric background, whereas the microscopic details of the background play the role of irrelevant perturbations not affecting criticality. PMID- 26991163 TI - Minimax Quantum Tomography: Estimators and Relative Entropy Bounds. AB - A minimax estimator has the minimum possible error ("risk") in the worst case. We construct the first minimax estimators for quantum state tomography with relative entropy risk. The minimax risk of nonadaptive tomography scales as O(1/sqrt[N]) in contrast to that of classical probability estimation, which is O(1/N)-where N is the number of copies of the quantum state used. We trace this deficiency to sampling mismatch: future observations that determine risk may come from a different sample space than the past data that determine the estimate. This makes minimax estimators very biased, and we propose a computationally tractable alternative with similar behavior in the worst case, but superior accuracy on most states. PMID- 26991164 TI - Cavity-Enhanced Room-Temperature Broadband Raman Memory. AB - Broadband quantum memories hold great promise as multiplexing elements in future photonic quantum information protocols. Alkali-vapor Raman memories combine high bandwidth storage, on-demand readout, and operation at room temperature without collisional fluorescence noise. However, previous implementations have required large control pulse energies and have suffered from four-wave-mixing noise. Here, we present a Raman memory where the storage interaction is enhanced by a low finesse birefringent cavity tuned into simultaneous resonance with the signal and control fields, dramatically reducing the energy required to drive the memory. By engineering antiresonance for the anti-Stokes field, we also suppress the four wave-mixing noise and report the lowest unconditional noise floor yet achieved in a Raman-type warm vapor memory, (15+/-2)*10^{-3} photons per pulse, with a total efficiency of (9.5+/-0.5)%. PMID- 26991165 TI - Finite-Time Fluctuations for the Totally Asymmetric Exclusion Process. AB - The one-dimensional totally asymmetric simple exclusion process, a Markov process describing classical hard-core particles hopping in the same direction, is considered on a periodic lattice of L sites. The relaxation to the nonequilibrium steady state, which occurs on the time scale t~L^{3/2} for large L, is studied for the half-filled system with N=L/2 particles. Using large L asymptotics of Bethe ansatz formulas for the eigenstates, exact expressions depending explicitly on the rescaled time t/L^{3/2} are obtained for the average and two-point function of the local density, and for the current fluctuations for simple (stationary, flat and step) initial conditions, relating previous results for the infinite system to stationary large deviations. The final formulas have a nice interpretation in terms of a functional integral with the action of a scalar field in a linear potential. PMID- 26991166 TI - Detecting Large Quantum Fisher Information with Finite Measurement Precision. AB - We propose an experimentally accessible scheme to determine the lower bounds on the quantum Fisher information (QFI), which ascertains multipartite entanglement or usefulness for quantum metrology. The scheme is based on comparing the measurement statistics of a state before and after a small unitary rotation. We argue that, in general, the limited resolution of collective observables prevents the detection of large QFI. This can be overcome by performing an additional operation prior to the measurement. We illustrate the power of this protocol for present-day spin-squeezing experiments, where the same operation used for the preparation of the initial spin-squeezed state improves also the measurement precision and hence the lower bound on the QFI by 2 orders of magnitude. We also establish a connection to the Leggett-Garg inequalities. We show how to simulate a variant of the inequalities with our protocol and demonstrate that large QFI is necessary for their violation with coarse-grained detectors. PMID- 26991167 TI - Supertranslations and Superrotations at the Black Hole Horizon. AB - We show that the asymptotic symmetries close to nonextremal black hole horizons are generated by an extension of supertranslations. This group is generated by a semidirect sum of Virasoro and Abelian currents. The charges associated with the asymptotic Killing symmetries satisfy the same algebra. When considering the special case of a stationary black hole, the zero mode charges correspond to the angular momentum and the entropy at the horizon. PMID- 26991168 TI - Leptogenesis from Left-Handed Neutrino Production during Axion Inflation. AB - We propose that the observed matter-antimatter asymmetry can be naturally produced as a by-product of axion-driven slow-roll inflation by coupling the axion to standard model neutrinos. We assume that grand unified theory scale right-handed neutrinos are responsible for the masses of the standard model neutrinos and that the Higgs field is light during inflation and develops a Hubble-scale root-mean-square value. In this setup, the rolling axion generates a helicity asymmetry in standard model neutrinos. Following inflation, this helicity asymmetry becomes equal to a net lepton number as the Higgs condensate decays and is partially reprocessed by the SU(2)_{L} sphaleron into a net baryon number. PMID- 26991169 TI - Constraint on Defect and Boundary Renormalization Group Flows. AB - A conformal field theory (CFT) in dimension d>=3 coupled to a planar, two dimensional, conformal defect is characterized in part by a "central charge" b that multiplies the Euler density in the defect's Weyl anomaly. For defect renormalization group flows, under which the bulk remains critical, we use reflection positivity to show that b must decrease or remain constant from the ultraviolet to the infrared. Our result applies also to a CFT in d=3 flat space with a planar boundary. PMID- 26991170 TI - Boosting the Direct CP Measurement of the Higgs-Top Coupling. AB - Characterizing the 125 GeV Higgs boson is a critical component of the physics program at the LHC Run II. In this Letter, we consider tt[over -]H associated production in the dileptonic mode. We demonstrate that the difference in azimuthal angle between the leptons from top decays can directly reveal the CP structure of the top-Higgs coupling with the sensitivity of the measurement substantially enhanced in the boosted Higgs regime. We first show how to access this channel via H->bb[over -] jet-substructure tagging, then demonstrate the ability of the new variable to measure CP. Our analysis includes all signal and background samples simulated via the MC@NLO algorithm including hadronization and underlying-event effects. Using a boosted Higgs substructure with dileptonic tops, we find that the top-Higgs coupling strength and the CP structure can be directly probed with achievable luminosity at the 13 TeV LHC. PMID- 26991171 TI - Finite Nuclei in the Quark-Meson Coupling Model. AB - We report the first use of the effective quark-meson coupling (QMC) energy density functional (EDF), derived from a quark model of hadron structure, to study a broad range of ground state properties of even-even nuclei across the periodic table in the nonrelativistic Hartree-Fock+BCS framework. The novelty of the QMC model is that the nuclear medium effects are treated through modification of the internal structure of the nucleon. The density dependence is microscopically derived and the spin-orbit term arises naturally. The QMC EDF depends on a single set of four adjustable parameters having a clear physics basis. When applied to diverse ground state data the QMC EDF already produces, in its present simple form, overall agreement with experiment of a quality comparable to a representative Skyrme EDF. There exist, however, multiple Skyrme parameter sets, frequently tailored to describe selected nuclear phenomena. The QMC EDF set of fewer parameters, derived in this work, is not open to such variation, chosen set being applied, without adjustment, to both the properties of finite nuclei and nuclear matter. PMID- 26991172 TI - Observation and Calculation of the Quasibound Rovibrational Levels of the Electronic Ground State of H2+. AB - Although the existence of quasibound rotational levels of the X^{+} ^{2}Sigma_{g}^{+} ground state of H_{2}^{+} was predicted a long time ago, these states have never been observed. Calculated positions and widths of quasibound rotational levels located close to the top of the centrifugal barriers have not been reported either. Given the role that such states play in the recombination of H(1s) and H^{+} to form H_{2}^{+}, this lack of data may be regarded as one of the largest unknown aspects of this otherwise accurately known fundamental molecular cation. We present measurements of the positions and widths of the lowest-lying quasibound rotational levels of H_{2}^{+} and compare the experimental results with the positions and widths we calculate using a potential model for the X^{+} state of H_{2}^{+} which includes adiabatic, nonadiabatic, relativistic, and radiative corrections to the Born-Oppenheimer approximation. PMID- 26991173 TI - Anomalously Large Chiral Sensitivity in the Dissociative Electron Attachment of 10-Iodocamphor. AB - We have studied dissociative electron attachment (DEA) between low energy (<=0.6 eV) longitudinally polarized electrons and gas-phase chiral targets of 3 bromocamphor (C_{10}H_{15}BrO), 3-iodocamphor (C_{10}H_{15}IO), and 10 iodocamphor. The DEA rate depends on the sign of the incident electron helicity for a given target handedness, and it varies with both the atomic number (Z) and location of the heaviest atom in the molecule. While simple dynamic mechanisms can account for the asymmetry dependence on Z, they fail to explain the large asymmetry variation with the heavy atom location. PMID- 26991174 TI - Photonic Circuits with Time Delays and Quantum Feedback. AB - We study the dynamics of photonic quantum circuits consisting of nodes coupled by quantum channels. We are interested in the regime where the time delay in communication between the nodes is significant. This includes the problem of quantum feedback, where a quantum signal is fed back on a system with a time delay. We develop a matrix product state approach to solve the quantum stochastic Schrodinger equation with time delays, which accounts in an efficient way for the entanglement of nodes with the stream of emitted photons in the waveguide, and thus the non-Markovian character of the dynamics. We illustrate this approach with two paradigmatic quantum optical examples: two coherently driven distant atoms coupled to a photonic waveguide with a time delay, and a driven atom coupled to its own output field with a time delay as an instance of a quantum feedback problem. PMID- 26991175 TI - Deterministic Squeezed States with Collective Measurements and Feedback. AB - We demonstrate the creation of entangled, spin-squeezed states using a collective, or joint, measurement and real-time feedback. The pseudospin state of an ensemble of N=5*10^{4} laser-cooled ^{87}Rb atoms is deterministically driven to a specified population state with angular resolution that is a factor of 5.5(8) [7.4(6) dB] in variance below the standard quantum limit for unentangled atoms-comparable to the best enhancements using only unitary evolution. Without feedback, conditioning on the outcome of the joint premeasurement, we directly observe up to 59(8) times [17.7(6) dB] improvement in quantum phase variance relative to the standard quantum limit for N=4*10^{5} atoms. This is one of the largest reported entanglement enhancements to date in any system. PMID- 26991176 TI - Valley Vortex States in Sonic Crystals. AB - Valleytronics is quickly emerging as an exciting field in fundamental and applied research. In this Letter, we study the acoustic version of valley states in sonic crystals and reveal a vortex nature of such states. In addition to the selection rules established for exciting valley polarized states, a mimicked valley Hall effect of sound is proposed further. The extraordinary chirality of valley vortex states, detectable in experiments, may open a new possibility in sound manipulations. This is appealing to scalar acoustics that lacks a spin degree of freedom inherently. In addition, the valley selection enables a handy way to create vortex matter in acoustics, in which the vortex chirality can be controlled flexibly. Potential applications can be anticipated with the exotic interaction of acoustic vortices with matter, such as to trigger the rotation of the trapped microparticles without contact. PMID- 26991177 TI - 2D-Omnidirectional Hard-X-Ray Scattering Sensitivity in a Single Shot. AB - X-ray scattering imaging can provide complementary information to conventional absorption based radiographic imaging about the unresolved microstructures of a sample. The scattering signal can be accessed with various methods based on coherent illumination, which span from self-imaging to speckle scanning. The directional sensitivity of the existing real space imaging methods is limited to a few directions on the imaging plane and requires scanning of the optical components, or the rotation of either the sample or the imaging setup, in order to cover the full range of possible scattering directions. In this Letter the authors propose a new method that allows the simultaneous acquisition of scattering images in all possible directions in a single shot. This is achieved by a specialized phase grating and a detector with sufficient spatial resolution to record the generated interference fringe. The structural length scale sensitivity of the system can be tuned by varying its geometry for a fixed grating design. Taking into account ongoing developments in the field of compact x-ray sources that allow high brightness and sufficient spatial coherence, the applicability of omnidirectional scattering imaging in industrial and medical settings is boosted significantly. PMID- 26991178 TI - Necessity of Time-Reversal Symmetry Breaking for the Polar Kerr Effect in Linear Response. AB - We show that, measured in a backscattering geometry, the polar Kerr effect is absent if the nonlocal electromagnetic response function respects Onsager symmetry, characteristic of thermodynamic states that preserve time-reversal symmetry. A key element is an expression for the reflectivity tensor in terms of the retarded Green's function. PMID- 26991179 TI - Superresolution Imaging of Optical Vortices in a Speckle Pattern. AB - We characterize, experimentally, the intensity minima of a polarized high numerical aperture optical speckle pattern and the topological charges of the associated optical vortices. The negative of a speckle pattern is imprinted in a uniform fluorescent sample by photobleaching. The remaining fluorescence is imaged with superresolution stimulated emission depletion microscopy, which reveals subdiffraction fluorescence confinement at the center of optical vortices. The intensity statistics of saturated negative speckle patterns are predicted and measured. The charge of optical vortices is determined by controlling the handedness of circular polarization, and the creation or annihilation of a vortex pair along propagation is shown. PMID- 26991180 TI - Observation of Critical-Gradient Behavior in Alfven-Eigenmode-Induced Fast-Ion Transport. AB - Experiments in the DIII-D tokamak show that fast-ion transport suddenly becomes stiff above a critical threshold in the presence of many overlapping small amplitude Alfven eigenmodes (AEs). The threshold is phase-space dependent and occurs when particle orbits become stochastic due to resonances with AEs. Above threshold, equilibrium fast-ion density profiles are unchanged despite increased drive, and intermittent fast-ion losses are observed. Fast-ion Dalpha spectroscopy indicates radially localized transport of the copassing population at radii that correspond to the location of midcore AEs. The observation of stiff fast-ion transport suggests that reduced models can be used to effectively predict alpha profiles, beam ion profiles, and losses to aid in the design of optimized scenarios for future burning plasma devices. PMID- 26991181 TI - Low-to-High Confinement Transition Mediated by Turbulence Radial Wave Number Spectral Shift in a Fusion Plasma. AB - A new model for the low-to-high (L-H) confinement transition has been developed based on a new paradigm for turbulence suppression by velocity shear [G. M. Staebler et al., Phys. Rev. Lett. 110, 055003 (2013)]. The model indicates that the L-H transition can be mediated by a shift in the radial wave number spectrum of turbulence, as evidenced here, for the first time, by the direct observation of a turbulence radial wave number spectral shift and turbulence structure tilting prior to the L-H transition at tokamak edge by direct probing. This new mechanism does not require a pretransition overshoot in the turbulent Reynolds stress, shunting turbulence energy to zonal flows for turbulence suppression as demonstrated in the experiment. PMID- 26991182 TI - Nonthermal Electron Energization from Magnetic Reconnection in Laser-Driven Plasmas. AB - The possibility of studying nonthermal electron energization in laser-driven plasma experiments of magnetic reconnection is studied using two- and three dimensional particle-in-cell simulations. It is demonstrated that nonthermal electrons with energies more than an order of magnitude larger than the initial thermal energy can be produced in plasma conditions currently accessible in the laboratory. Electrons are accelerated by the reconnection electric field, being injected at varied distances from the X points, and in some cases trapped in plasmoids, before escaping the finite-sized system. Trapped electrons can be further energized by the electric field arising from the motion of the plasmoid. This acceleration gives rise to a nonthermal electron component that resembles a power-law spectrum, containing up to ~8% of the initial energy of the interacting electrons and ~24% of the initial magnetic energy. Estimates of the maximum electron energy and of the plasma conditions required to observe suprathermal electron acceleration are provided, paving the way for a new platform for the experimental study of particle acceleration induced by reconnection. PMID- 26991183 TI - Energetic Geodesic Acoustic Modes Associated with Two-Stream-like Instabilities in Tokamak Plasmas. AB - An unstable branch of the energetic geodesic acoustic mode (EGAM) is found using fluid theory with fast ions characterized by their narrow width in energy distribution and collective transit along field lines. This mode, with a frequency much lower than the thermal GAM frequency omega_{GAM}, is now confirmed as a new type of unstable EGAM: a reactive instability similar to the two-stream instability. The mode can have a very small fast ion density threshold when the fast ion transit frequency is smaller than omega_{GAM}, consistent with the onset of the mode right after the turn-on of the beam in DIII-D experiments. The transition of this reactive EGAM to the velocity gradient driven EGAM is also discussed. PMID- 26991184 TI - Condensing Magnons in a Degenerate Ferromagnetic Spinor Bose Gas. AB - We observe the quasicondensation of magnon excitations within an F=1 ^{87}Rb spinor Bose-Einstein condensed gas. Magnons are pumped into a ferromagnetically ordered gas, allowed to equilibrate to a nondegenerate distribution, and then cooled evaporatively at near-constant net longitudinal magnetization, whereupon they condense. The critical magnon number, spatial distribution, and momentum distribution indicate that magnons condense in a potential that is uniform within the volume of the ferromagnetic condensate. The macroscopic transverse magnetization produced by the degenerate magnon gas remains inhomogeneous within the ~10 s equilibration time accessed in our experiment, and includes signatures of Mermin-Ho spin textures that appear as phase singularities in the magnon quasicondensate wave function. PMID- 26991185 TI - How Water Advances on Superhydrophobic Surfaces. AB - Superliquid repellency can be achieved by nano- and microstructuring surfaces in such a way that protrusions entrap air underneath the liquid. It is still not known how the three-phase contact line advances on such structured surfaces. In contrast to a smooth surface, where the contact line can advance continuously, on a superliquid-repellent surface, the contact line has to overcome an air gap between protrusions. Here, we apply laser scanning confocal microscopy to get the first microscopic videos of water drops advancing on a superhydrophobic array of micropillars. In contrast to common belief, the liquid surface gradually bends down until it touches the top face of the next micropillars. The apparent advancing contact angle is 180 degrees . On the receding side, pinning to the top faces of the micropillars determines the apparent receding contact angle. Based on these observations, we propose that the apparent receding contact angle should be used for characterizing superliquid-repellent surfaces rather than the apparent advancing contact angle and hysteresis. PMID- 26991186 TI - Submolecular Resolution Imaging of Molecules by Atomic Force Microscopy: The Influence of the Electrostatic Force. AB - The forces governing the contrast in submolecular resolution imaging of molecules with atomic force microscopy (AFM) have recently become a topic of intense debate. Here, we show that the electrostatic force is essential to understand the contrast in atomically resolved AFM images of polar molecules. Specifically, we image strongly polarized molecules with negatively and positively charged tips. A contrast inversion is observed above the polar groups. By taking into account the electrostatic forces between tip and molecule, the observed contrast differences can be reproduced using a molecular mechanics model. In addition, we analyze the height dependence of the various force components contributing to the high resolution AFM contrast. PMID- 26991187 TI - Chiral Magnetic Effect and Anomalous Hall Effect in Antiferromagnetic Insulators with Spin-Orbit Coupling. AB - We search for dynamical magnetoelectric phenomena in three-dimensional correlated systems with spin-orbit coupling. We focus on the antiferromagnetic insulator phases where the dynamical axion field is realized by the fluctuation of the antiferromagnetic order parameter. It is shown that the dynamical chiral magnetic effect, an alternating current generation by magnetic fields, emerges due to such time dependences of the order parameter as antiferromagnetic resonance. It is also shown that the anomalous Hall effect arises due to such spatial variations of the order parameter as antiferromagnetic domain walls. Our study indicates that spin excitations in antiferromagnetic insulators with spin-orbit coupling can result in nontrivial charge responses. Moreover, observing the chiral magnetic effect and anomalous Hall effect in our system is equivalent to detecting the dynamical axion field in condensed matter. PMID- 26991188 TI - Coexistence of Incommensurate Magnetism and Superconductivity in the Two Dimensional Hubbard Model. AB - We analyze the competition of magnetism and superconductivity in the two dimensional Hubbard model with a moderate interaction strength, including the possibility of incommensurate spiral magnetic order. Using an unbiased renormalization group approach, we compute magnetic and superconducting order parameters in the ground state. In addition to previously established regions of Neel order coexisting with d-wave superconductivity, the calculations reveal further coexistence regions where superconductivity is accompanied by incommensurate magnetic order. PMID- 26991189 TI - Two-Dimensional pi-Conjugated Covalent-Organic Frameworks as Quantum Anomalous Hall Topological Insulators. AB - The quantum anomalous Hall (QAH) insulator is a novel topological state of matter characterized by a nonzero quantized Hall conductivity without an external magnetic field. Using first-principles calculations, we predict the QAH state in monolayers of covalent-organic frameworks based on the newly synthesized X_{3}(C_{18}H_{12}N_{6})_{2} structure where X represents 5d transition metal elements Ta, Re, and Ir. The pi conjugation between X d_{xz} and d_{yz} orbitals, mediated by N p_{z} and C p_{z} orbitals, gives rise to a massive Dirac spectrum in momentum space with a band gap of up to 24 meV due to strong spin-orbit coupling. We show that the QAH state can appear by chemically engineering the exchange field and the Fermi level in the monolayer structure, resulting in nonzero Chern numbers. Our results suggest a reliable pathway toward the realization of a QAH phase at temperatures between 100 K and room temperature in covalent-organic frameworks. PMID- 26991190 TI - Spin to Charge Conversion at Room Temperature by Spin Pumping into a New Type of Topological Insulator: alpha-Sn Films. AB - We present results on spin to charge current conversion in experiments of resonant spin pumping into the Dirac cone with helical spin polarization of the elemental topological insulator (TI) alpha-Sn. By angle-resolved photoelectron spectroscopy (ARPES), we first check that the Dirac cone (DC) at the alpha-Sn (0 0 1) surface subsists after covering Sn with Ag. Then we show that resonant spin pumping at room temperature from Fe through Ag into alpha-Sn layers induces a lateral charge current that can be ascribed to the inverse Edelstein effect by the DC states. Our observation of an inverse Edelstein effect length much longer than those generally found for Rashba interfaces demonstrates the potential of TIs for the conversion between spin and charge in spintronic devices. By comparing our results with data on the relaxation time of TI free surface states from time-resolved ARPES, we can anticipate the ultimate potential of the TI for spin to charge conversion and the conditions to reach it. PMID- 26991191 TI - Spin Polarization and Texture of the Fermi Arcs in the Weyl Fermion Semimetal TaAs. AB - A Weyl semimetal is a new state of matter that hosts Weyl fermions as quasiparticle excitations. The Weyl fermions at zero energy correspond to points of bulk-band degeneracy, called Weyl nodes, which are separated in momentum space and are connected only through the crystal's boundary by an exotic Fermi arc surface state. We experimentally measure the spin polarization of the Fermi arcs in the first experimentally discovered Weyl semimetal TaAs. Our spin data, for the first time, reveal that the Fermi arcs' spin-polarization magnitude is as large as 80% and lies completely in the plane of the surface. Moreover, we demonstrate that the chirality of the Weyl nodes in TaAs cannot be inferred by the spin texture of the Fermi arcs. The observed nondegenerate property of the Fermi arcs is important for establishing its exact topological nature, which reveals that spins on the arc form a novel type of 2D matter. Additionally, the nearly full spin polarization we observed (~80%) may be useful in spintronic applications. PMID- 26991192 TI - Competition between Kondo Screening and Quantum Hall Edge Reconstruction. AB - We report on a Kondo correlated quantum dot connected to two-dimensional leads where we demonstrate the renormalization of the g factor in the pure Zeeman case. i.e., for magnetic fields parallel to the plane of the quantum dot. For the same system, we study the influence of orbital effects by investigating the quantum Hall regime; i.e., a perpendicular magnetic field is applied. In this case an unusual behavior of the suppression of the Kondo effect and of the split zero bias anomaly is observed. The splitting decreases with magnetic field and shows discontinuous changes that are attributed to the intricate interplay between Kondo screening and the quantum Hall edge structure originating from electrostatic screening. This edge structure, made up of compressible and incompressible stripes, strongly affects the Kondo temperature of the quantum dot and thereby influences the renormalized g factor. PMID- 26991193 TI - Observation of Thermoelectric Currents in High-Field Superconductor-Ferromagnet Tunnel Junctions. AB - We report on the experimental observation of spin-dependent thermoelectric currents in superconductor-ferromagnet tunnel junctions in high magnetic fields. The thermoelectric signals are due to a spin-dependent lifting of the particle hole symmetry, and are found to be in excellent agreement with recent theoretical predictions. The maximum Seebeck coefficient inferred from the data is about -100 MUV/K, much larger than commonly found in metallic structures. Our results directly prove the coupling of spin and heat transport in high-field superconductors. PMID- 26991194 TI - Thermoelectric Signatures of Time-Reversal Symmetry Breaking States in Multiband Superconductors. AB - We show that superconductors with broken time-reversal symmetry have very specific magnetic and electric responses to inhomogeneous heating. A local heating of such superconductors induces a magnetic field with a profile that is sensitive to the presence of domain walls and crystalline anisotropy of superconducting states. A nonstationary heating process produces an electric field and a charge imbalance in different bands. These effects can be measured and used to distinguish s+is and s+id superconducting states in the candidate materials such as Ba_{1-x}K_{x}Fe_{2}As_{2}. PMID- 26991195 TI - Spin Hall Magnetoresistance in Metallic Bilayers. AB - Spin Hall magnetoresistance (SMR) is studied in metallic bilayers that consist of a heavy metal (HM) layer and a ferromagnetic metal (FM) layer. We find a nearly tenfold increase of SMR in W/CoFeB compared to previously studied HM/ferromagnetic insulator systems. The SMR increases with decreasing temperature despite the negligible change in the W layer resistivity. A model is developed to account for the absorption of the longitudinal spin current to the FM layer, one of the key characteristics of a metallic ferromagnet. We find that the model not only quantitatively describes the HM layer thickness dependence of SMR, allowing accurate estimation of the spin Hall angle and the spin diffusion length of the HM layer, but also can account for the temperature dependence of SMR by assuming a temperature dependent spin polarization of the FM layer. These results illustrate the unique role a metallic ferromagnetic layer plays in defining spin transmission across the HM/FM interface. PMID- 26991196 TI - Correlation Length versus Gap in Frustration-Free Systems. AB - Hastings established exponential decay of correlations for ground states of gapped quantum many-body systems. A ground state of a (geometrically) local Hamiltonian with spectral gap epsilon has correlation length xi upper bounded as xi=O(1/epsilon). In general this bound cannot be improved. Here we study the scaling of the correlation length as a function of the spectral gap in frustration-free local Hamiltonians, and we prove a tight bound xi=O(1/sqrt[epsilon]) in this setting. This highlights a fundamental difference between frustration-free and frustrated systems near criticality. The result is obtained using an improved version of the combinatorial proof of correlation decay due to Aharonov, Arad, Vazirani, and Landau. PMID- 26991197 TI - Full Electroresistance Modulation in a Mixed-Phase Metallic Alloy. AB - We report a giant, ~22%, electroresistance modulation for a metallic alloy above room temperature. It is achieved by a small electric field of 2 kV/cm via piezoelectric strain-mediated magnetoelectric coupling and the resulting magnetic phase transition in epitaxial FeRh/BaTiO_{3} heterostructures. This work presents detailed experimental evidence for an isothermal magnetic phase transition driven by tetragonality modulation in FeRh thin films, which is in contrast to the large volume expansion in the conventional temperature-driven magnetic phase transition in FeRh. Moreover, all the experimental results in this work illustrate FeRh as a mixed-phase model system well similar to phase-separated colossal magnetoresistance systems with phase instability therein. PMID- 26991198 TI - Antiferromagnetic Spin Seebeck Effect. AB - We report on the observation of the spin Seebeck effect in antiferromagnetic MnF_{2}. A device scale on-chip heater is deposited on a bilayer of MnF_{2} (110) (30 nm)/Pt (4 nm) grown by molecular beam epitaxy on a MgF_{2} (110) substrate. Using Pt as a spin detector layer, it is possible to measure the thermally generated spin current from MnF_{2} through the inverse spin Hall effect. The low temperature (2-80 K) and high magnetic field (up to 140 kOe) regime is explored. A clear spin-flop transition corresponding to the sudden rotation of antiferromagnetic spins out of the easy axis is observed in the spin Seebeck signal when large magnetic fields (>9 T) are applied parallel to the easy axis of the MnF_{2} thin film. When the magnetic field is applied perpendicular to the easy axis, the spin-flop transition is absent, as expected. PMID- 26991200 TI - Quasi-Long-Range Order and Vortex Lattice in the Three-State Potts Model. AB - We show that the order-disorder phase transition in the three-state Potts ferromagnet on a square lattice is driven by a coupled proliferation of domain walls and vortices. Raising the vortex core energy above a threshold value decouples the proliferation and splits the transition into two. The phase between the two transitions exhibits an emergent U(1) symmetry and quasi-long-range order. Lowering the core energy below a threshold value also splits the order disorder transition but the system forms a vortex lattice in the intermediate phase. PMID- 26991199 TI - Origin of the Spin-Orbital Liquid State in a Nearly J=0 Iridate Ba_{3}ZnIr_{2}O_{9}. AB - We show using detailed magnetic and thermodynamic studies and theoretical calculations that the ground state of Ba_{3}ZnIr_{2}O_{9} is a realization of a novel spin-orbital liquid state. Our results reveal that Ba_{3}ZnIr_{2}O_{9} with Ir^{5+} (5d^{4}) ions and strong spin-orbit coupling (SOC) arrives very close to the elusive J=0 state but each Ir ion still possesses a weak moment. Ab initio density functional calculations indicate that this moment is developed due to superexchange, mediated by a strong intradimer hopping mechanism. While the Ir spins within the structural Ir_{2}O_{9} dimer are expected to form a spin-orbit singlet state (SOS) with no resultant moment, substantial frustration arising from interdimer exchange interactions induce quantum fluctuations in these possible SOS states favoring a spin-orbital liquid phase down to at least 100 mK. PMID- 26991201 TI - Control of the Ultrafast Photoinduced Magnetization across the Morin Transition in DyFeO_{3}. AB - Excitation of the collinear compensated antiferromagnet DyFeO_{3} with a single 60 fs laser pulse triggers a phase transition across the Morin point into a noncollinear spin state with a net magnetization. Time-resolved imaging of the magnetization dynamics of this process reveals that the pulse first excites the spin oscillations upon damping of which the noncollinear spin state emerges. The sign of the photoinduced magnetization is defined by the relative orientation of the pump polarization and the direction of the antiferromagnetic vector in the initial collinear spin state. PMID- 26991202 TI - Structural Transition in a Fluid of Spheroids: A Low-Density Vestige of Jamming. AB - A thermodynamically equilibrated fluid of hard spheroids is a simple model of liquid matter. In this model, the coupling between the rotational degrees of freedom of the constituent particles and their translations may be switched off by a continuous deformation of a spheroid of aspect ratio t into a sphere (t=1). We demonstrate, by experiments, theory, and computer simulations, that dramatic nonanalytic changes in structure and thermodynamics of the fluids take place, as the coupling between rotations and translations is made to vanish. This nonanalyticity, reminiscent of a second-order liquid-liquid phase transition, is not a trivial consequence of the shape of an individual particle. Rather, free volume considerations relate the observed transition to a similar nonanalyticity at t=1 in structural properties of jammed granular ellipsoids. This observation suggests a deep connection to exist between the physics of jamming and the thermodynamics of simple fluids. PMID- 26991204 TI - Equilibrium Phase Behavior of a Continuous-Space Microphase Former. AB - Periodic microphases universally emerge in systems for which short-range interparticle attraction is frustrated by long-range repulsion. The morphological richness of these phases makes them desirable material targets, but our relatively coarse understanding of even simple models hinders controlling their assembly. We report here the solution of the equilibrium phase behavior of a microscopic microphase former through specialized Monte Carlo simulations. The results for cluster crystal, cylindrical, double gyroid, and lamellar ordering qualitatively agree with a Landau-type free energy description and reveal the nontrivial interplay between cluster, gel, and microphase formation. PMID- 26991203 TI - Emergent Collective Chemotaxis without Single-Cell Gradient Sensing. AB - Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments show that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior is observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this "collective guidance," and study a model based on this mechanism both analytically and computationally. Our approach posits that contact inhibition of locomotion, where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how the cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance. PMID- 26991205 TI - Structures and Dynamics of Glass-Forming Colloidal Liquids under Spherical Confinement. AB - Recent theories predict that when a supercooled liquid approaches the glass transition, particle clusters with a special "amorphous order" nucleate within the liquid, which lead to static correlations dictating the dramatic slowdown of liquid relaxation. The prediction, however, has yet to be verified in 3D experiments. Here, we design a colloidal system, where particles are confined inside spherical cavities with an amorphous layer of particles pinned at the boundary. Using this novel system, we capture the amorphous-order particle clusters and demonstrate the development of a static correlation. Moreover, by investigating the dynamics of spherically confined samples, we reveal a profound influence of the static correlation on the relaxation of colloidal liquids. In analogy to glass-forming liquids with randomly pinned particles, we propose a simple relation for the change of the configurational entropy of confined colloidal liquids, which quantitatively explains our experimental findings and illustrates a divergent static length scale during the colloidal glass transition. PMID- 26991206 TI - Interfacial Molecular Searching Using Forager Dynamics. AB - Many biological and technological systems employ efficient non-Brownian intermittent search strategies where localized searches alternate with long flights. Coincidentally, molecular species exhibit intermittent behavior at the solid-liquid interface, where periods of slow motion are punctuated by fast flights through the liquid phase. Single-molecule tracking was used here to observe the interfacial search process of DNA for complementary DNA. Measured search times were qualitatively consistent with an intermittent-flight model, and ~10 times faster than equivalent Brownian searches, suggesting that molecular searches for reactive sites benefit from similar efficiencies as biological organisms. PMID- 26991207 TI - Erratum: Ultrahigh Bandwidth Spin Noise Spectroscopy: Detection of Large g-Factor Fluctuations in Highly-n-Doped GaAs [Phys. Rev. Lett. 111, 186602 (2013)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.111.186602. PMID- 26991208 TI - Simulated herbivory does not constrain phenotypic plasticity to shade through ontogeny in a relict tree. AB - Ecological limits to phenotypic plasticity (PP), induced by simultaneous biotic and abiotic factors, can prevent organisms from exhibiting optimal plasticity, and in turn lead to decreased fitness. Herbivory is an important biotic stressor and may limit plant functional responses to challenging environmental conditions such as shading. In this study we investigated whether plant functional responses and PP to shade are constrained by herbivory, and whether such constraints are due to direct effects based on resource limitation by considering ontogeny. We used as a model system the relict tree Prunus lusitanica and implemented an indoor experiment to quantify the response of saplings of different ages to shade and herbivory. We measured five functional traits and quantitatively calculated PP. Results showed that herbivory did not constrain functional responses or PP to shade except for shoot:root ratio (SR), which, despite showing a high PP in damaged saplings, decreased under shade instead of increasing. Damaged saplings of older age did not exhibit reduced constraints on functional responses to shade and generally presented a lower PP than damaged saplings of younger age. Our findings suggest that herbivory-mediated constraints on plant plasticity to shade may not be as widespread as previously thought. Nonetheless, the negative effect of herbivory on SR plastic expression to shade could be detrimental for plant fitness. Finally, our results suggest a secondary role of direct effects (resource-based) on P. lusitanica plasticity limitation. Further studies should quantify plant resources in order to gain a better understanding of this seldom explored subject. PMID- 26991209 TI - Firefly Luciferase Mutants Allow Substrate-Selective Bioluminescence Imaging in the Mouse Brain. AB - Bioluminescence imaging is a powerful approach for visualizing specific events occurring inside live mice. Animals can be made to glow in response to the expression of a gene, the activity of an enzyme, or the growth of a tumor. But bioluminescence requires the interaction of a luciferase enzyme with a small molecule luciferin, and its scope has been limited by the mere handful of natural combinations. Herein, we show that mutants of firefly luciferase can discriminate between natural and synthetic substrates in the brains of live mice. When using adeno-associated viral (AAV) vectors to express luciferases in the brain, we found that mutant luciferases that are inactive or weakly active with d-luciferin can light up brightly when treated with the aminoluciferins CycLuc1 and CycLuc2 or their respective FAAH-sensitive luciferin amides. Further development of selective luciferases promises to expand the power of bioluminescence and allow multiple events to be imaged in the same live animal. PMID- 26991210 TI - New photosensitive nanometric graphite oxide composites as antimicrobial material with prolonged action. AB - A new conjugate material based on partially reduced graphite oxide (rGO), silver nanoparticles (Ag), and bis(lysinato)zirconium(IV) phthalocyanine complex (ZrPc) was obtained. Its optical properties (absorption and photoluminescence) after dispersion in solvents were examined. The antimicrobial properties were tested to determine the effect of the composite on the following bacterial strains: Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, which are responsible for many infections and are one of the pathogens the most difficult to treatment. The results obtained for rGO-ZrPc-Ag composite were compared with the properties of GO, GO-ZrPc, and rGO-Ag structures. The influence of the near infrared irradiation on the antimicrobial activity of ZrPc- and Ag-doped materials against bacteria was observed for very low concentration (0.32mg/mL) of GO-ZrPc to stop the growth of P. aeruginosa in comparison to the nonirradiated sample (41mg/mL). The usefulness of this material in therapy, such as wound infection treatment or endodontic treatment, as antibacterial agent with sustained action was discussed. PMID- 26991211 TI - Pilomatrixoma is a diagnostic trap in fine-needle aspiration cytology of the parotid region. PMID- 26991212 TI - Characterization of Tack Strength Based on Cavity-Growth Criterion. AB - The adhesive force generated by a small short-term pressure, called tack, is measured by a probe tack test on pressure-sensitive adhesives (PSAs); the maximum force is evaluated by cavity growth at the interface between the PSA layer and the probe surface. As the PSA layer becomes thinner, it is more difficult to measure the tack with a cylindrical probe because of the uneven contact resulting from misalignment. A spherical probe is preferable to obtain reproducible contact on the PSA layer, but the contact area should be taken into account if the contact pressure affects the tack performance. Tack was measured on PSAs with various thicknesses in different contact areas to clarify their effect. The results showed that a larger contact area on a thinner PSA generated higher adhesive stress with larger strain. It was found that the maximum adhesive stress was not affected by the contact pressure, but it was strongly correlated to the contact radius divided by the PSA thickness. In addition, a video microscope observation showed that, in all of the experimental cases, the adhesive stress always reached the maximum when cavities were generated at the interface between the PSA and probe surface. Therefore, the criterion of cavity growth was introduced for the evaluation of the maximum adhesive stress. As a result, the experimental results, even at different release rates, were in good agreement with the estimation by considering the effect of confining a thin layer. Furthermore, the theoretical estimation indicated the ultimate value, which was not dependent upon the PSA thickness or contact area. It was defined as a material property, referred to as the "ultimate tack strength" of PSAs. PMID- 26991213 TI - World Voice Day 2016. PMID- 26991214 TI - Endolymphatic sac tumor in association with von Hippel-Lindau syndrome. PMID- 26991215 TI - Ectopic thyroid tissue simulating metastasis. PMID- 26991216 TI - Rhinosporidiosis. PMID- 26991217 TI - Medial orbital wall reconstruction with a porous polyethylene titan barrier implant. PMID- 26991218 TI - The economic impact of revision otologic surgery. AB - Revision otologic surgery places a significant economic burden on patients and the healthcare system. We conducted a retrospective chart analysis to estimate the economic impact of revision canal-wall-down (CWD) mastoidectomy. We reviewed the medical records of all 189 adults who had undergone CWD mastoidectomy performed by the senior author between June 2006 and August 2011 at Loyola University Medical Center in Maywood, Ill. Institutional charges and collections for all patients were extrapolated to estimate the overall healthcare cost of revision surgery in Illinois and at the national level. Of the 189 CWD mastoidectomies, 89 were primary and 100 were revision procedures. The total charge for the revision cases was $2,783,700, and the net reimbursement (collections) was $846,289 (30.4%). Using Illinois Hospital Association data, we estimated that reimbursement for 387 revision CWD mastoidectomies that had been performed in fiscal year 2011 was nearly $3.3 million. By extrapolating our data to the national level, we estimated that 9,214 patients underwent revision CWD mastoidectomy in the United States during 2011, which cost the national healthcare system roughly $76 million, not including lost wages and productivity. Known causes of failed CWD mastoidectomies that often result in revision surgery include an inadequate meatoplasty, a facial ridge that is too high, residual diseased air cells, and recurrent cholesteatoma. A better understanding of these factors can reduce the need for revision surgery, which could have a positive impact on the economic strain related to this procedure at the local, state, and national levels. PMID- 26991219 TI - Otogenic lateral sinus thrombosis in children: A review of 7 cases. AB - Otogenic lateral sinus thrombosis (LST) is a rare but serious intracranial complication of acute or chronic otitis media. Reported mortality rates have ranged from 8 to 25%; the pediatric mortality rate might be as low as 5%. Controversy still exists over the medical and surgical management of this condition. We conducted a retrospective chart review of 7 cases of pediatric otogenic LST that were treated at our institution over a period of 8 years. We hypothesized that good outcomes in very sick patients can be achieved by aggressively managing the mastoid cavity and without the need for a thrombectomy. Our study group was made up of 4 boys and 3 girls, aged 6 to 15 years (mean: 11.1). All patients received intravenous antibiotics and underwent mastoidectomy with unroofing of the sigmoid sinus and placement of a tympanostomy tube. Sinus exploration with thrombectomy was not performed in any patient. Anticoagulation was used perioperatively in 5 patients (71%) without complication. All patients recovered well without major sequelae, which supports our hypothesis. We also describe the case of a patient with multiple concomitant intracranial comorbidities associated with this rare condition. PMID- 26991220 TI - Is the emergency department management of ENT foreign bodies successful? A tertiary care hospital experience in Australia. AB - We evaluated the role of the emergency department (ED) in the management of ear, nose, and throat foreign bodies in an Australian tertiary care hospital. We retrospectively reviewed all cases of ENT foreign-body presentations in the ED over a 2-year period. We identified 168 such cases, a large proportion of which involved pediatric patients. In addition to demographic factors, we also collected data on the nature of the foreign bodies, the specific sites involved, the rate of successful treatment by the ED staff, the seniority/rank of the treating clinician, and complications. Foreign bodies in the ear accounted for 49% of all cases, the nose for 43%, and the throat for 8%. The ED staff attempted to remove the foreign body in 89% of cases, while the rest were referred to the ENT team. The rate of successful removal of all foreign bodies attempted by the ED team was fairly high-78%; success rates were 86% for nasal foreign bodies, 72% for aural objects, and 67% for those lodged in the throat. No major complications occurred; minor bleeding episodes after removal occurred in 8% of cases. Most ENT foreign-body presentations were managed safely and entirely by the ED team; most of the ENT referrals were to outpatient clinics. PMID- 26991221 TI - Metastatic pilomatrix carcinoma: Not so rare after all? A case report and review of the literature. AB - Pilomatrixoma is a slowly growing benign tumor of the dermal hair cells. Metastatic disease is exceptionally rare. Pilomatrixoma can occur at any age, but most patients are older than 40 years at presentation. Approximately 60% of these lesions occur in the head and neck region. Their size is usually about 4 cm at the time of presentation. Surgical excision with adequate margins is still the preferred treatment. We report a case of an aggressive malignant metastatic pilomatrixoma in a 43-year-old woman who underwent multiple extensive local resections. However, she died within 4 months of presentation. PMID- 26991222 TI - Surgical treatment of superior laryngeal neuralgia: A case report and review of the literature. AB - Superior laryngeal (SL) neuralgia is paroxysmal pain above the thyrohyoid membrane. We present a case of SL neuralgia that was resistant to conservative treatment and eventually required surgical intervention. The patient was a 39 year-old woman with a 5-year history of debilitating pain above the thyroid cartilage. After having undergone different imaging scans with negative results, she tried various treatments (e.g., antibiotics, analgesics, stellate ganglion block, radiofrequency SL neurotomy, and stereotactic radiosurgery), all of which were ineffective. Finally, she underwent bilateral surgical SL neurotomy. Postoperatively, she immediately noticed a significant alleviation of her pain. Her postoperative course was completely uneventful, as she experienced no dysphagia or dysphonia, even transiently. One month later, she no longer required regular painkillers, and at 14 months, she remained essentially pain-free. While medical management remains the treatment of choice for SL neuralgia, we recommend that refractory cases be treated initially with a neural block with local anesthesia. Patients who do not respond are candidates for surgery. We consider selective peripheral SL neurotomy to be safe and effective when performed by experienced hands. We also discuss the difficulties of managing SL neuralgia. PMID- 26991223 TI - The effects of round window membrane injury and the use of a model electrode application on hearing in rats. AB - We conducted an animal experiment to investigate the effects of mechanical trauma to the round window with the placement of a model electrode inserted into the scala tympani on the cochlear reserve, and to determine the efficacy of topical steroids in preventing hearing loss in such a situation. Our subjects included 21 male Wistar albino rats that were assigned into three groups of 7 each. In all three groups, an initial mechanical injury to the round window was created. At that point, group 1 received no further treatment, group 2 received a dexamethasone injection into the cochlea, and group 3 underwent implantation of a multichannel cochlear implant guide followed by dexamethasone administration. After a few minutes, the round window opening was obliterated with muscle, and the incision was sutured with 4-0 Vicryl Rapide polyglactin in all 3 groups. Distortion-product otoacoustic emissions were obtained before and immediately after the surgical injury, and again on postoperative day 7. Mean signal/noise ratios (S/Ns) obtained at 2, 3, and 4 kHz were calculated, and datasets were compared with nonparametric statistical tests. We found that the early postoperative mean S/N values were significantly lower than the preoperative values in groups 1 and 2, but there was no difference between the mean preoperative values and those obtained on postoperative day 7 in those two groups. In group 3, there were statistically significant differences among the mean preoperative, early postoperative, and postoperative day 7 S/N values. We observed that an electrode insertion into the cochlea via the round window subsequent to mechanical trauma seemed to cause a progressive hearing loss. Therefore, we conclude that special care must be taken to avoid injury to the round window membrane during placement of a cochlear implant electrode, as well as during surgery for chronic otitis media. PMID- 26991224 TI - Stapediovestibular ankylosis in an HIV/HCV-copositive patient. AB - To the best of the author's knowledge, no case of a patient with stapediovestibular ankylosis who was also coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) has been previously described in the literature. This report describes the case of a 36-year-old woman who was diagnosed with all three conditions. The clinical diagnosis of stapes fixation was based on otoscopic, audiometric, tympanometric, and surgical findings. Stapedectomy was performed, and perilymph and serum samples were obtained and tested for anti-HIV and anti-HCV antibodies. While the titers of anti-HCV antibodies in the serum and perilymph were of similar magnitude, there were almost 16 times more anti-HIV antibodies in the serum than in the perilymph. This case offered a unique opportunity to study the titers of anti-HIV/HCV antibodies in both the blood serum and perilymph. Data relating to these titers may provide new insights into the mechanisms of stapediovestibular ankylosis and inner ear immunology. PMID- 26991225 TI - Respiratory epithelial adenomatoid hamartoma of the olfactory groove: A report of 4 cases and a review of the literature. AB - Respiratory epithelial adenomatoid hamartoma (REAH) is a rare benign lesion that affects the nasal cavity and paranasal sinuses. We present 4 cases of REAH that involved the olfactory clefts; 1 case was bilateral. Each of the cases was treated surgically, and no recurrence was observed. Most reports have indicated that REAH occurs in the presence of sinonasal inflammation, particularly nasal polyposis, yet all 4 of our cases occurred in the absence of concurrent rhinosinusitis. This suggests that the etiology of REAH is multifactorial. In addition, we review the literature on REAH, and we discuss its presentation, differential diagnosis, radiology, histopathology, and underlying treatment principles. PMID- 26991226 TI - A case of minocycline-induced black thyroid associated with papillary carcinoma. AB - We report a rare case of black thyroid accompanied by papillary carcinoma in a patient with an extended history of minocycline treatment. A 78-year-old man was referred to our outpatient clinic with swelling in his neck. He had been taking minocycline for the previous 2 years and 7 months to treat chronic perianal pyoderma. Neck ultrasonography and computed tomography demonstrated a 3.5 * 3.7 * 5.0-cm nodule in the left thyroid lobe, and fine-needle aspiration cytology identified it as a papillary carcinoma. The patient underwent a total thyroidectomy and neck dissection. During the procedure, a distinct black discoloration of the thyroid parenchyma was observed. Histopathology confirmed both the black thyroid and the papillary carcinoma. Based on the thyroid gland's discoloration and the history of minocycline use, the patient was diagnosed with minocycline-induced black thyroid. He was symptom-free 20 months after surgery. PMID- 26991227 TI - Myxoinflammatory fibroblastic sarcoma of the nose: First reported case at an unusual location (nasal dorsum), with a review of the literature. AB - Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade, malignant, soft-tissue tumor that typically affects the distal extremities of middle-aged patients. In most cases, it presents as a painless, slowly growing mass within the subcutaneous tissue. It is associated with a low rate of metastasis but a high rate of local recurrence. In addition to the distal extremities, MIFS has been reported in the thigh, arm, forearm, groin, upper back, neck, and temporal area. As far as we know, no case has been previously reported in the nasal area. We report for the first time a case of MIFS presenting on the dorsum of the nose. The painless, 3.0-cm tumor was initially mistaken for reticular erythematous mucinosis, a benign skin condition that occurs when fibroblasts produce abnormally large amounts of mucopolysaccharides. The tumor was surgically removed in its entirety with surgical margins of 3 to 5 mm. During 4 years of follow-up, no clinical or radiologic evidence of a recurrence or metastasis was seen. We discuss the imaging and histologic features of MIFS, as well as its clinical management and follow-up, and we review related reports in the literature. PMID- 26991228 TI - Papillary carcinoma in thyroglossal duct cyst: Two case reports and review of the literature. AB - The thyroglossal duct cyst is one of the more common congenital anterior neck masses. In rare cases, carcinoma has been detected within one of these cysts on histopathologic analysis of resected tissue. Since the incidence of thyroglossal duct cyst carcinoma is low, the appropriate management of the thyroid gland proper is not algorithmic. We present 2 cases of papillary thyroid carcinoma that were discovered in a thyroglossal duct cyst, and we describe the diagnostic and therapeutic measures taken in each case. Particular attention is paid to two points: (1) fine-needle aspiration biopsy may not be sufficient to rule out carcinoma and (2) removal of the thyroid gland may be advisable in selected situations. PMID- 26991229 TI - A limited thoracocervical approach for accessing the anterior mediastinum in retrosternal goiters: Surgical technique and implications for the management of head and neck emergencies. AB - In this article we describe the surgical management of retrosternal goiters via a limited thoracocervical approach, and we explore how the respective surgical know how can be used in the management of the carotid blowout syndrome. Four cases involving patients who had undergone thyroidectomy via a limited thoracocervical approach are retrospectively reviewed. An acute blowout of the innominate artery managed with the same principal surgical technique is also reviewed. Three patients had a total thyroidectomy and one had a hemithyroidectomy. No malignancy was found. There was no mortality or unexpected morbidity from the limited thoracocervical approach. The median length of the inpatient stay was 3 days. The blowout survivor lived for 9 months, with no rebleeding and with an acceptable quality of life. We conclude that a limited thoracocervical approach can be safely performed by head and neck surgeons for accessing the anterior mediastinum in retrosternal goiters, and the respective surgical know-how can be used in the immediate management of an acute carotid blowout syndrome with satisfying long term results and provision of quality end-of-life care. PMID- 26991230 TI - Bilateral intubation granulomas. PMID- 26991231 TI - Simultaneous occurrence of maxillary and sphenoid sinus fungus ball. PMID- 26991232 TI - Helicobacter pylori in lacrimal secretions. AB - The aim of this study was to investigate the presence of Helicobacter pylori in human lacrimal and nasal secretions. Eighty patients with complaints of dyspepsia who had undergone endoscopies and gastric antrum biopsies were included in the study. A total of five specimens, including 2 lacrimal secretion samples, 2 nasal mucosal swab samples, and 1 gastric antrum biopsy, were collected from each patient and investigated with polymerase chain reaction (PCR) methods consisting of the urease enzyme coding gene GlmM (UreC) and the H pylori-specific 16S rRNA coding gene. The Reflux Symptom Index and ophthalmologic complaints of the patients were recorded. The detected positivity rates of the H pylori 16S rRNA coding gene in gastric biopsies and nasal mucous and lacrimal secretions were 55, 11.2, and 20%, respectively. The patients were grouped as gastric-antrum-biopsy negative (Group I [n = 36]) and -positive (Group II [n = 44). In Group II, H pylori positivity in the lacrimal and nasal mucous secretions was 36.3 and 18%, respectively. A comparison between the groups in terms of H pylori presence in nasal mucous and lacrimal secretions yielded statistically significant differences (p = 0.0001, p = 0.003). The simultaneous presence of H pylori in nasal mucous and lacrimal secretions was 13.6% in Group II. H pylori positivity in nasal mucous and lacrimal secretions had a positive moderate correlation (r = 0.40; p = 0.0003). The present study is the first report on the presence of H pylori in lacrimal secretions through nested PCR, which suggested the presence of a number of mechanisms for H pylori transmission to lacrimal secretions. PMID- 26991233 TI - Evaluation of sire by environment interactions for growth rate and backfat depth using reaction norm models in pigs. AB - Reaction norm models for sires were used to evaluate genotype by environment interactions for lifetime average daily gain (ADG) and backfat depth (BF) in pigs recorded at 143 days. Data for ADG and BF were available for 265 103 pigs recorded in Australia between 2000 and 2010 in nine herds. The full data set and two subsets based on minimum numbers of progeny per sire of 50 and 100 were analysed. The environmental descriptor was quantified as least square means of herd-by-birth month (HBM) contemporary groups which varied from 540 to 738 g/day for ADG and from 8.2 to 13.8 mm for BF. Several models were evaluated for estimation of variance components in terms of predictive ability for sire intercepts and slopes. The accuracy of genetic parameter estimates was improved by increasing family size, fitting models with a fixed regression coefficient on the environmental descriptor instead of fixed HBM effects and heterogeneous residual variances. Significant sire by environment interactions were found for ADG but not for BF. Heritability estimates for ADG ranged from approximately 0.21 in average environments to approximately 0.30 in the most unfavourable environments. Estimates of sire intercepts and slopes varied by 98.5 g/day and 0.253 g/day per g/day for ADG, respectively. Lowly negative correlations between sire intercept and slope do not support the hypothesis that high growth is associated with larger environmental sensitivity. PMID- 26991234 TI - Effects of food price shocks on child malnutrition: The Mozambican experience 2008/2009. AB - A propitiously timed household survey carried out in Mozambique over the period 2008/2009 permits us to study the relationship between shifts in food prices and child nutrition status in a low income setting. We focus on weight-for-height and weight-for-age in different survey quarters characterized by very different food price inflation rates. Using propensity score matching techniques, we find that these nutrition measures, which are sensitive in the short run, improve significantly in the fourth quarter of the survey, when the inflation rate for basic food products is low, compared to the first semester or three quarters, when food price inflation was generally high. The prevalence of underweight, in particular, falls by about 40 percent. We conclude that the best available evidence points to food penury, driven by the food and fuel price crisis combined with a short agricultural production year, as substantially increasing malnutrition amongst under-five children in Mozambique. PMID- 26991235 TI - Myricitrin Ameliorates 6-Hydroxydopamine-Induced Dopaminergic Neuronal Loss in the Substantia Nigra of Mouse Brain. AB - Parkinson's disease (PD) is a chronic and progressive movement disorder, resulting from the degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of DA neuronal loss in PD is still unclear; however, accumulating evidence suggests that treatment with certain flavonoids can induce neuroprotective properties, such as activation of mammalian target of rapamycin complex 1 (mTORC1) and anti-inflammatory activities in animal models of PD. The bioflavonoid myricitrin is well known for its anti-inflammatory and antioxidant properties. However, it is unclear whether systemic treatment with myricitrin can protect neurons against neurotoxin-induced DA degeneration in vivo via the preservation of tyrosine hydroxylase (TH) activity and the induction of mTORC1 activation. Our results found no significant neuroprotective effect of 30 mg/kg myricitrin on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the substantia nigra (SN) of mice. However, myricitrin treatment with 60 mg/kg protected DA neurons against 6-OHDA-induced neurotoxicity. Moreover, myricitrin treatment preserved TH enzyme activity and mTORC1 activation in nigral DA neurons in the SN of 6-OHDA-treated mice, and its treatment suppressed an increase in tumor necrosis factor-alpha expression in activated microglia. These results suggest that myricitrin may have neuroprotective properties linked to mTORC1 activation, preservation of TH enzyme activity, and anti-neuroinflammation for preventing DA neuronal degeneration in vivo. PMID- 26991236 TI - The expansion of brown rot disease throughout Bolivia: possible role of climate change. AB - Bacterial wilt is a devastating plant disease caused by the bacterial pathogen Ralstonia solanacearum species complex and affects different crops. Bacterial wilt infecting potato is also known as brown rot (BR) and is responsible for significant economic losses in potato production, especially in developing countries. In Bolivia, BR affects up to 75% of the potato crop in areas with high incidence and 100% of stored potatoes. The disease has disseminated since its introduction to the country in the mid-1980s mostly through contaminated seed tubers. To avoid this, local farmers multiply seed tubers in highlands because the strain infecting potatoes cannot survive near-freezing temperatures that are typical in the high mountains. Past disease surveys have shown an increase in seed tubers with latent infection in areas at altitudes lower than 3000 m a.s.l. Since global warming is increasing in the Andes Mountains, in this work, we explored the incidence of BR in areas at altitudes above 3000 m a.s.l. Results showed BR presence in the majority of these areas, suggesting a correlation between the increase in disease incidence and the increase in temperature and the number of irregular weather events resulting from climate change. However, it cannot be excluded that the increasing availability of latently infected seed tubers has boosted the spread of BR. PMID- 26991237 TI - Identification of multiple lipid genes with modifications in expression and sequence associated with the evolution of hydroxy fatty acid accumulation in Physaria fendleri. AB - Two Brassicaceae species, Physaria fendleri and Camelina sativa, are genetically very closely related to each other and to Arabidopsis thaliana. Physaria fendleri seeds contain over 50% hydroxy fatty acids (HFAs), while Camelina sativa and Arabidopsis do not accumulate HFAs. To better understand how plants evolved new biochemical pathways with the capacity to accumulate high levels of unusual fatty acids, transcript expression and protein sequences of developing seeds of Physaria fendleri, wild-type Camelina sativa, and Camelina sativa expressing a castor bean (Ricinus communis) hydroxylase were analyzed. A number of potential evolutionary adaptations within lipid metabolism that probably enhance HFA production and accumulation in Physaria fendleri, and, in their absence, limit accumulation in transgenic tissues were revealed. These adaptations occurred in at least 20 genes within several lipid pathways from the onset of fatty acid synthesis and its regulation to the assembly of triacylglycerols. Lipid genes of Physaria fendleri appear to have co-evolved through modulation of transcriptional abundances and alterations within protein sequences. Only a handful of genes showed evidence for sequence adaptation through gene duplication. Collectively, these evolutionary changes probably occurred to minimize deleterious effects of high HFA amounts and/or to enhance accumulation for physiological advantage. These results shed light on the evolution of pathways for novel fatty acid production in seeds, help explain some of the current limitations to accumulation of HFAs in transgenic plants, and may provide improved strategies for future engineering of their production. PMID- 26991239 TI - Use of posttreatment imaging and biomarker testing for survivors of breast cancer. PMID- 26991238 TI - A real-world study focused on the long-term efficacy of mycophenolate mofetil as first-line treatment of autoimmune hepatitis. AB - BACKGROUND: Front-line therapy with mycophenolate mofetil (MMF) in autoimmune hepatitis (AIH) has shown high on-treatment remission rates. AIM: To study prospectively in a real-world fashion the long-term outcome of a large group of consecutive treatment-naive AIH patients. METHODS: Between 2000 and 2014, 158 patients were recruited but only 131 were eligible for treatment (109 MMF/prednisolone; 22 prednisolone +/- azathioprine). Long-term data on outcome after drug withdrawal were evaluated. Patients stopped treatment after having achieved complete response (normal transaminases and IgG) for at least the last 2 years. RESULTS: At diagnosis, 31.6% of patients had cirrhosis and 72.8% insidious presentation. A total of 102 of 109 (93.6%) responded initially to MMF within 2 (1-18) months. A total of 78 of 109 (71.6%) had complete response on treatment and 61 of 78 (78.2%) maintained remission off prednisolone. MMF-treated patients had increased probability of complete response compared to those receiving azathioprine (P = 0.03). Independent predictors of complete response were lower ALT at 6 months (P = 0.001) and acute presentation (P = 0.03). So far, treatment withdrawal was feasible in 40/109 patients and 30 (75%) are still in remission after 24 (2-129) months. Remission maintenance was associated with longer MMF treatment (P = 0.005), higher baseline ALT (P < 0.02), lower IgG on 6 months (P = 0.004) and histological improvement. CONCLUSIONS: Mycophenolate mofetil proved to be an efficient first-line treatment for AIH, achieving so far the highest rates of remission maintenance off treatment (75%) ever published for at least a median of 2 years, although the remission criteria used were strict. However, the risk of potential bias and overestimation of intervention benefits from MMF cannot be completely excluded as this is a real world and not a randomised controlled trial. PMID- 26991240 TI - Cdc42-dependent F-actin dynamics drive structuration of the demarcation membrane system in megakaryocytes. AB - Essentials Information about the formation of the demarcation membrane system (DMS) is still lacking. We investigated the role of the cytoskeleton in DMS structuration in megakaryocytes. Cdc42/Pak-dependent F-actin remodeling regulates DMS organization for proper megakaryopoiesis. These data highlight the mandatory role of F-actin in platelet biogenesis. SUMMARY: Background Blood platelet biogenesis results from the maturation of megakaryocytes (MKs), which involves the development of a complex demarcation membrane system (DMS). Therefore, MK differentiation is an attractive model for studying membrane remodeling. Objectives We sought to investigate the mechanism of DMS structuration in relationship to the cytoskeleton. Results Using three-dimensional (3D) confocal imaging, we have identified consecutive stages of DMS organization that rely on F actin dynamics to polarize membranes and nuclei territories. Interestingly, microtubules are not involved in this process. We found that the mechanism underlying F-actin-dependent DMS formation required the activation of the guanosine triphosphate hydrolase Cdc42 and its p21-activated kinase effectors (Pak1/2/3). Forster resonance energy transfer demonstrated that active Cdc42 was associated with endomembrane dynamics throughout terminal maturation. Inhibition of Cdc42 or Pak1/2/3 severely destructured the DMS and blocked proplatelet formation. Even though this process does not require containment within the hematopoietic niche, because DMS structuration was observed upon thrombopoietin treatment in suspension, integrin outside-in signaling was required for Pak activation and probably resulted from secretion of extracellular matrix by MKs. Conclusions These data indicate a functional link, mandatory for MK differentiation, between actin dynamics, regulated by Cdc42/Pak1/2/3, and DMS maturation. PMID- 26991241 TI - Asymmetric Retro-Claisen Reaction by Chiral Primary Amine Catalysis. AB - The communication describes an enamine-based asymmetric retro-Claisen reaction of beta-diketones by primary amine catalysis. The reaction proceeds via a sequence of stereoselective C-C formation, C-C cleavage, and a highly stereospecific enamine protonation to afford chiral alpha-alkylated ketones or macrolides with high yields and enantioselectivities. A detailed mechanism was explored on the basis of experimental evidence and computational studies to account for the observed stereocontrol. PMID- 26991242 TI - Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery. AB - Significant progress has been made in prospectively designing molecules using the central nervous system multiparameter optimization (CNS MPO) desirability tool, as evidenced by the analysis reported herein of a second wave of drug candidates that originated after the development and implementation of this tool. This simple-to-use design algorithm has expanded design space for CNS candidates and has further demonstrated the advantages of utilizing a flexible, multiparameter approach in drug discovery rather than individual parameters and hard cutoffs of physicochemical properties. The CNS MPO tool has helped to increase the percentage of compounds nominated for clinical development that exhibit alignment of ADME attributes, cross the blood-brain barrier, and reside in lower-risk safety space (low ClogP and high TPSA). The use of this tool has played a role in reducing the number of compounds submitted to exploratory toxicity studies and increasing the survival of our drug candidates through regulatory toxicology into First in Human studies. Overall, the CNS MPO algorithm has helped to improve the prioritization of design ideas and the quality of the compounds nominated for clinical development. PMID- 26991243 TI - "The Worst Experience of My Life": The Internship Crisis and Its Impact on Students. AB - OBJECTIVE: The objective of the present study was to understand how internship applicants perceive themselves as being affected by the ongoing imbalance between the number of internship spots available and the number of applicants to internship. METHOD: The present study undertook a qualitative, and supplemental quantitative, analysis of 1,076 internship applicant responses to an item included in the 2011 postmatch survey asking participants how the internship crisis has affected them. RESULTS: Results indicated that the internship application process in general was viewed overwhelmingly negatively. Respondents described personal stress and system issues in their responses. Respondents described reciprocal stresses; applications spur on stresses, which are compounded by fears of not matching. Such fears cast negative light on training. Participants also described resiliencies that buffered against stresses and perceptions of discrimination or bias that add to stress. CONCLUSIONS: The implications of these findings for supporting students, working to resolve the internship crisis, and adapting policy are discussed. PMID- 26991244 TI - CRISPR-Cas-Assisted Multiplexing (CAM): Simple Same-Day Multi-Locus Engineering in Yeast. AB - Demands on the industrial and academic yeast strain engineer have increased significantly in the era of synthetic biology. Installing complex biosynthetic pathways and combining point mutations are tedious and time-consuming using traditional methods. With multiplex engineering tools, these tasks can be completed in a single step, typically achieving up to sixfold compression in strain engineering timelines. To capitalize on this potential, a variety of yeast CRISPR-Cas methods have been developed, differing largely in how the guide RNA (gRNA) reagents that direct the Cas9 nuclease are delivered. However, in nearly all reported protocols, the time savings of multiplexing is offset by multiple days of cloning to prepare the required reagents. Here, we discuss the advantages and opportunities of CRISPR-Cas-assisted multiplexing (CAM), a same-day, cloning free method for multi-locus engineering in yeast. J. Cell. Physiol. 231: 2563 2569, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991246 TI - Interventions for molluscum contagiosum in people infected with human immunodeficiency virus: a systematic review. AB - BACKGROUND: Molluscum contagiosum (MC) is a viral skin disease that presents with white, painless papules with central umbilication. In immunocompent individuals, MC is usually a benign infection that resolves without intervention. In HIV positive people, symptoms of MC can be more severe. OBJECTIVE: The aim of this systematic review is to analyze the literature on strategies for treating MC in people concomitantly infected with HIV and subsequently make recommendations on best management strategies for these people. METHOD: Searches were conducted of the following electronic databases: MEDLINE, EMBASE, Cochrane Library, PubMed, LILACS, IndMED, Global Health, ClinicalTrials.Gov, and Current Controlled Trials. Grey literature was searched via the New York Academy of Medicine Grey Literature Report and Open Grey. References cited in previous reviews and references cited in studies identified as being possibly relevant were also reviewed. No language restrictions were imposed. Papers from 1980 to present were reviewed. RESULTS & DISCUSSION: Thirteen studies were included in this review. Two papers were comparative studies, one of which was randomized and neither of which were blinded. Ten papers were observational studies with heterogeneous populations. One study was a multicentre cohort study. CONCLUSION: Given the poor quality of study design, wide array of outcome variables, and lack of objective evidence, no specific recommendation can be made for the treatment of MC in people infected with HIV, other than the initiation of ART. Despite the good impact ART has made on prevalence of dermatologic disease, MC remains an important cause of morbidity in HIV positive populations. PMID- 26991247 TI - Polarized Raman scattering and SEM combined full characterization of self assembled nematic thin films. AB - Elongated particles are predestined for a fast transfer of optical and electronical signals in a preferred direction, which is mandatory for a quick response in optoelectronic devices. The performance of the material is based on the quality of defect less alignment of the particles. On this account we present an easy non-invasive methodology for characterization of both surface and bulk order. The characterization of bulk order is performed by orientation dependent variation of the polarized Raman scattering signal on large areas by mapping. Scanning electron microscopy and image analysis on the surface complete the characterization. New insights in dip coated nematic structures clearly show the interplay of evaporation induced and shear-induced self-assembly and reveal a comprehensive mechanistic picture for nanorod assembly: the shear force dominated regime orients the particle in direction of withdrawal. At low withdrawal velocity, however, shear forces and evaporation counteract to produce a three layered film where the top and bottom layers are oriented perpendicular to each other. The middle layer gives a clear evidence for a reorientation by convective flow. PMID- 26991245 TI - Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High-Density Lipoprotein-Enriched Serum in Rheumatoid Arthritis. AB - OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA. METHODS: A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n = 23], ADA [n = 22], or TCZ [n = 25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP-1 macrophages, and total cellular cholesterol was measured by fluorometric assay. RESULTS: The DAS28-ESR decreased with all treatments (P < 0.001). Net cholesterol efflux capacity was not significantly changed after 6 months of new RA therapy (mean +/- SD 36.9 +/- 17.3% units at baseline versus 38.0% +/- 16.9% units at 6 months [P = 0.58]). However, change in net cholesterol efflux capacity was associated with change in the DAS28-ESR (rho = -0.25, P = 0.04). In a post hoc analysis of patients with impaired net cholesterol efflux capacity at baseline, treatment with TCZ resulted in significant improvement in net cholesterol efflux capacity (21.9 +/- 14.7% units at baseline versus 31.3% +/- 12.8% units at 6 months [P < 0.02]), but this was not observed with MTX or ADA. CONCLUSION: Net cholesterol efflux capacity of HDL cholesterol did not change significantly after 6 months of new RA therapy, except in patients with impaired baseline cholesterol efflux capacity who were receiving TCZ. Change in disease activity was associated with change in the net cholesterol efflux capacity. PMID- 26991248 TI - An Injectable Self-Assembling Collagen-Gold Hybrid Hydrogel for Combinatorial Antitumor Photothermal/Photodynamic Therapy. AB - An injectable and self-healing collagen-gold hybrid hydrogel is spontaneously formed by electrostatic self-assembly and subsequent biomineralization. It is demonstrated that such collagen-based hydrogels may be used as an injectable material for local delivery of therapeutic agents, showing enhanced antitumor efficacy. PMID- 26991249 TI - Splenic immunotoxicity in developing cane toads (Rhinella marina) from Bermuda. AB - The impacts of contaminated sediment from 2 ponds in Bermuda on immune function in newly metamorphosed cane toads were examined. In the present study, a partial life-cycle experiment exposing Gosner stage 20 cane toad tadpoles to pond sediment and laboratory culture water through metamorphosis and into a juvenile state was performed. A basic immunology battery, including general necropsy, spleen somatic index, spleen white pulp content, splenocyte tissue density, and splenocyte viability, was conducted in newly metamorphosed Rhinella marina exposed to Bermuda freshwater sediment and baseline specimens collected from 2 separate populations in south Texas and south Florida, USA. Immune function was evaluated using a lymphocyte proliferation assay with subset specimens infected with Mycobacterium chelonae. In the Bermuda population exposed to pond sediment, splenocyte tissue density was markedly lower and lymphocyte proliferation substantially less relative to cohorts exposed to control sediment and to the North American populations. Considerable increases in spleen weight and liver and spleen lesions related to M. chelonae infection were recorded in challenged Bermuda R. marina compared with unchallenged specimens. Overall, immune function in Bermuda R. marina was compromised compared with North American mainland R. marina regardless of treatment but more dramatically in specimens exposed to Bermuda pond sediments. Environ Toxicol Chem 2016;35:2604-2612. (c) 2016 SETAC. PMID- 26991250 TI - Protein interacting with NIMA (never in mitosis A)-1 regulates axonal growth cone adhesion and spreading through myristoylated alanine-rich C kinase substrate isomerization. AB - Axonal growth cone motility requires precise regulation of adhesion to navigate the complex environment of the nervous system and reach its target. Myristoylated alanine-rich C kinase substrate (MARCKS) protein is enriched in the developing brain and plays an important, phosphorylation-dependent role in the modulation of axonal growth cone adhesion. The ratio of phospho-MARCKS (MARCKS-P) to total MARCKS controls adhesion modulation and spreading of the axonal growth cone. Pin1, a peptidyl-prolyl cis/trans isomerase (PPIase) that recognizes and binds to phosphorylated serine/threonine residues preceded by a proline (pSer/Thr-Pro) is also expressed in the developing brain. Here, we show that Pin1 is present in the growth cone, interacts with MARCKS-P, and regulates its dephosphorylation. We also described morphological alterations in the corpus callosum and cerebral cortex fibers of the Pin1 knockout mouse brain that may be caused by the misregulation of MARCKS-P and alterations of neuronal adhesion. We have shown that MARCKS, a critical protein in the movement of neuronal growth cones, is in turn regulated by both phosphorylation and cis-trans peptidyl isomerization mediated by Pin1. In the absence of Pin1, MARCKS is hyperphosphorylated, leading to loss of adhesions, and collapse of the growth cone. The Pin1 KO mice exhibited disturbed neuronal projections from the cerebral cortex and reduced white matter tracks such as the corpus callosum. This study highlights a novel function of Pin1 in neurodevelopment. PMID- 26991251 TI - Longitudinal association of obesity, metabolic syndrome and diabetes with risk of elevated aminotransferase levels in a cohort of Mexican health workers. AB - OBJECTIVE: In Mexico, chronic liver disease have been increasingly found along with the rapidly growing prevalence of obesity, diabetes and metabolic syndrome (MS). We aimed to investigate the longitudinal association between these three factors and risk of elevated alanine aminotransferase (ALT) levels (>40 U/L), a marker for liver damage, in a cohort of Mexican adults. METHODS: Data were obtained from two separate waves of the Mexican Health Worker Cohort Study: Wave 1 (2004-2006) and Wave 2 (2011-2013). Unconditional logistic regression models were employed to determine the cross-sectional and longitudinal association between these risk factors and elevated ALT levels. RESULTS: The prevalence of elevated ALT was significantly higher among men, individuals aged under 60 years, those who were overweight or obese, diabetic, with MS or heavy/binge drinkers. The longitudinal results indicated that weight gain between waves that resulted in a change in body mass index, along with remaining overweight or obese, were significantly associated with an increased risk of elevated ALT levels. A significantly increased risk of developing elevated ALT was also observed among those who acquired diabetes or MS from Wave 1 to Wave 2. CONCLUSIONS: Weight gain and acquiring diabetes or MS are associated with a significant risk of having elevated ALT. These results, within the context of the rapid increase in global obesity rates, call urgently for programs to help to prevent chronic liver disease. PMID- 26991254 TI - Copper(II)-Catalyzed Oxidative Cross-Coupling of Anilines, Primary Alkyl Amines, and Sodium Azide Using TBHP: A Route to 2-Substituted Benzimidazoles. AB - Copper(II)-catalyzed oxidative cross-coupling of anilines, primary alkyl amines, and sodium azide is described in the presence of TBHP at moderate temperature. This one-pot multicomponent protocol involves a domino C-H functionalization, transimination, ortho-selective amination, and a cyclization sequence. The broad substrate scope and functional group compatibility are the significant practical features. The protocol can be extended to the coupling of benzyl alcohols with moderate yields. PMID- 26991253 TI - The nursing role during end-of-life care in the intensive care unit related to the interaction between patient, family and professional: an integrative review. AB - AIM: The aim of this study was to explore how intensive care unit (ICU) nurses describe their role during End-of-Life Care (EOLC) in the ICU, related to the interaction between patient, family and professionals (care triad). METHOD: Three electronic databases, PubMed, CINAHL and EMBASE, and reference lists of included studies were searched for studies in English, Dutch or German between January 2002 and August 2015. Studies were included if they presented data about EOLC in the adult ICU, and the role of ICU nurses around EOLC. Quantitative and qualitative studies and opinion articles were extracted. Inductive content analysis was carried out to analyse and categorise the data. RESULTS: Twenty studies were included. Four categories emerged: care for the ICU patient, care for the family, environmental aspects of EOLC and organisational aspects of EOLC. Regarding the care triad, a gap exists between theoretical models and the actual care provided by ICU nurses during EOLC. The relational aspect of care, like aimed with care triad, is absent. CONCLUSION: The literature clearly indicates that the role of ICU nurses concerns care for the patient, family and environment. It described which care should be given, but it remains unclear how care should be given (attitude). Therefore, it is difficult for ICU nurses to provide this care. Further, it seems that care provided to family mainly consists of giving advice on how to care for the patient; care for family members themselves was only mentioned in a few studies. Therefore, it seems that family does not always receive adequate care yet, which may be helpful in preventing problems like depression, anxiety or post-traumatic stress disorder. It can be concluded that it is important for ICU nurses to be aware of the existing relationships; however, comparing the literature, care triad does not appear to be reached. PMID- 26991255 TI - Clinical impact of the hepatitis C virus mutations in the era of directly acting antivirals. AB - Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The majority of patients who did not achieve an SVR were found to be infected with HCV strains with a reduced susceptibility to these drugs. Indeed, the high error rate of the viral polymerase and a fast virion production (100 fold higher than the human immunodeficiency virus) result in a mixture of viral genetic populations (quasi-species) pre-existing treatment initiation. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A region and rarely in the NS5B region. Treatment-induced resistant mutants to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. This review focuses on the type and prevalence of viral strains with a reduced sensitivity to DAAs, their clinical impact and influence on the response to treatment and, consequently, on treatment choice for DAA-experienced patients. J. Med. Virol. 88:1659-1671, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991256 TI - The study of the function of AQP4 in cerebral ischaemia-reperfusion injury using poroelastic theory. AB - Brain oedema is thought to form and to clear through the use of water-protein channels, aquaporin-4 (AQP4), which are found in the astrocyte endfeet. The model developed here is used to study the function of AQP4 in the formation and elimination of oedema fluid in ischaemia-reperfusion injury. The cerebral space is assumed to be made of four fluid compartments: astrocyte, neuron, ECS and blood microvessels, and a solid matrix for the tissue, and this is modelled using multiple-network poroelastic theory. AQP4 allows the movement of water between astrocyte and the ECS and the microvessels. It is found that the presence of AQP4 may help in reducing vasogenic oedema shown by a decrease in brain tissue extracellular pressure. However, the astrocyte pressure will increase to compensate for this decrease, which may lead to cytotoxic oedema. In addition, the swelling will also depend on the ionic concentrations in the astrocyte and extracellular space, which may change after ischaemic stroke. Understanding the role of AQP4 in oedema may thus help the development of a treatment plan in reducing brain swelling after ischaemia-reperfusion. PMID- 26991257 TI - Are the Assessment of Spondyloarthritis International Society Classification Criteria Useful in Juvenile Spondyloarthritis? Comment on the Article by Weiss et al. PMID- 26991258 TI - Soluble receptor and gene polymorphism for AGE: relationship with obesity and cardiovascular risks. AB - BACKGROUND: Obesity in adolescents has quadrupled in the past 30 y. Markers for cardiovascular risks are needed in this population. We hypothesized that soluble receptor for advanced glycation end products (sRAGE) and asymmetric dimethyl arginine (ADMA) can correlate with carotid intima-media thickness (cIMT), a known index of subclinical atherosclerosis. We also aimed to evaluate the frequency of (Gly82Ser) RAGE gene polymorphism in obese adolescents. METHODS: Obese and nonobese adolescents were evaluated in a cross-sectional study for lipid profile, insulin resistance, ADMA, sRAGE, and RAGE gene (Gly 82 Ser) polymorphism. We measured cIMT in all subjects and performed correlation analyses with all markers. RESULTS: The study included 50 obese and 40 healthy control adolescents. Compared to controls, obese subjects had less sRAGE (P = 0.02) and greater cIMT (P = 0.006), insulin resistance (P < 0.0001), and ADMA (P < 0.0001). In a multivariate linear regression model, sRAGE was associated with cIMT (beta = 0.28, P = 0.04). Both GS and SS genotypes of RAGE were more frequent in obese than controls (P = 0.04). CONCLUSION: Increased ADMA and decreased sRAGE are associated with cardiovascular risks in obese adolescents. The S allele in RAGE gene is more frequently detected with obesity. The role of RAGE gene and mechanisms leading to cardiovascular risks need further studying. PMID- 26991259 TI - Optimizing lung aeration at birth using a sustained inflation and positive pressure ventilation in preterm rabbits. AB - BACKGROUND: A sustained inflation (SI) facilitates lung aeration, but the most effective pressure and duration are unknown. We investigated the effect of gestational age (GA) and airway liquid volume on the required inflation pressure and SI duration. METHODS: Rabbit kittens were delivered at 27, 29, and 30 d gestation, intubated and airway liquid was aspirated. Either no liquid (control) or 30 ml/kg of liquid was returned to the airways. Lung gas volumes were measured by plethysmography and phase-contrast X-ray-imaging. Starting at 22 cmH2O, airway pressure was increased until airflow commenced and pressure was then held constant. The SI was truncated when 20 ml/kg air had entered the lung and ventilation continued with intermittent positive pressure ventilation (iPPV). RESULTS: Higher SI pressures and longer durations were required in 27-d kittens compared to 30-d kittens. During iPPV, 27-d kittens needed higher pressures and had lower functional residual capacity (FRC) compared to 30-d kittens. Adding lung liquid increased SI duration, reduced FRC, and increased resistance and pressures during iPPV in 29- and 30-d kittens. CONCLUSION: Immature kittens required higher starting pressures and longer SI durations to achieve a set inflation volume. Larger airway liquid volumes adversely affected lung function during iPPV in older but not young kittens. PMID- 26991260 TI - Inhibition of beta-catenin signaling protects against CTGF-induced alveolar and vascular pathology in neonatal mouse lung. AB - BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of premature infants. Connective tissue growth factor (CTGF) plays an important role in tissue development and remodeling. We have previously shown that targeted overexpression of CTGF in alveolar type II epithelial cells results in BPD-like pathology and activates beta-catenin in neonatal mice. METHODS: Utilizing this transgenic mouse model and ICG001, a specific pharmacological inhibitor of beta-catenin, we tested the hypothesis that beta catenin signaling mediates the effects of CTGF in the neonatal lung. Newborn CTGF mice and control littermates received ICG001 (10 mg/kg/dose) or placebo (dimethyl sulfoxide, equal volume) by daily i.p. injection from postnatal day 5 to 15. Alveolarization, vascular development, and pulmonary hypertension (PH) were analyzed. RESULTS: Administration of ICG001 significantly downregulated expression of cyclin D1, collagen 1a1, and fibronectin, which are the known target genes of beta-catenin signaling in CTGF lungs. Inhibition of beta-catenin signaling improved alveolar and vascular development and decreased pulmonary vascular remodeling. More importantly, the improved vascular development and vascular remodeling led to a decrease in PH. CONCLUSION: beta-Catenin signaling mediates the autocrine and paracrine effects of CTGF in the neonatal lung. Inhibition of CTGF-beta-catenin signaling may provide a novel therapy for BPD. PMID- 26991261 TI - Functional and structural connectivity of the visual system in infants with perinatal brain injury. AB - BACKGROUND: Infants with perinatal brain injury are at risk of later visual problems. Advanced neuroimaging techniques show promise to detect functional and structural alterations of the visual system. We hypothesized that infants with perinatal brain injury would have less brain activation during a visual functional magnetic resonance imaging (fMRI) task and reduced task-based functional connectivity and structural connectivity as compared with healthy controls. METHODS: Ten infants with perinatal brain injury and 20 control infants underwent visual fMRI and diffusion tensor imaging (DTI) during natural sleep with no sedation. Activation maps, functional connectivity maps, and structural connectivity were analyzed and compared between the two groups. RESULTS: Most infants in both groups had negative activation in the visual cortex during the fMRI task. Infants with brain injury showed reduced activation in the occipital cortex, weaker connectivity between visual areas and other areas of the brain during the visual task, and reduced fractional anisotropy in white matter tracts projecting to visual regions, as compared with control infants. CONCLUSION: Infants with brain injury sustained in the perinatal period showed evidence of decreased brain activity and functional connectivity during a visual task and altered structural connectivity as compared with healthy term neonates. PMID- 26991262 TI - Liganded retinoic acid X receptor alpha represses connexin 43 through a potential retinoic acid response element in the promoter region. AB - INTRODUCTION: Retinoic acid X receptor alpha (RXRalpha) and Connexin 43 (Cx43) both play a crucial role in cardiogenesis. However, little is known about the interplay mechanism between the RXRalpha and Cx43. METHODS: The activations of retinoic acid response element (RARE) in Cx43 were measured by luciferase transfection assay. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) was performed to prove that RXRalpha can directly bind to the RARE sequence. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyze the RXRalpha and Cx43 mRNA level and protein level in cells. RESULTS: In this study, we confirmed the negative association of the gene expression between the RXRalpha and Cx43 in the cell level. Interestingly, a functional RARE was detected in the region from -1,426 to -314 base pairs upstream from the transcriptional start site of Cx43. Moreover, we also prove that RXRalpha can directly bind to this RARE sequence in vitro and in vivo. CONCLUSIONS: RXRalpha negatively regulates the transcription and expression by directly binding to the RARE in the promoter of Cx43. The RARE-like sequence harbored in the Cx43 promoter region may serve as a functional RARE in the retinoic acid (RA) signaling pathway. PMID- 26991263 TI - Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age. AB - BACKGROUND: Experimental evidence exists indicating that maternal thyroid hormones during pregnancy may affect the metabolic set point and cardio-vascular function in the offspring. The objective of this study was to investigate the association between maternal thyroid function in week 30 of gestation and offspring adiposity and blood pressure at 20 y. METHODS: The study was based on the follow up of a Danish birth cohort from 1988 to 1989 (n = 965). A blood sample was drawn from the pregnant women in week 30 of gestation (N = 877). In 2008-2009, the offspring were followed up with self-reported anthropometrics (N = 645) and a clinically measured blood pressure (N = 425). Multiple linear regressions were used to estimate the association between maternal thyroid function and offspring BMI, waist circumference, and blood pressure. RESULTS: Offspring of subclinical hypothyroid women had higher systolic blood pressure (adjusted difference = 3.6, 95% confidence interval: 0.2, 7.0 mmHg) and a tendency toward higher diastolic blood pressure (adjusted difference = 2.3, 95% confidence interval: -0.2, 4.9 mmHg) compared to offspring of euthyroid women. No association was found with offspring BMI and waist circumference. CONCLUSION: Maternal thyroid function during third trimester of pregnancy may affect long term blood pressure in the offspring. PMID- 26991264 TI - Effects of neonatal dexamethasone administration on cardiac recovery ability under ischemia-reperfusion in 24-wk-old rats. AB - BACKGROUND: Evaluations of stress-induced cardiac functional alterations in adults after neonatal glucocorticoid (GC) treatment have been limited. In the present study, we evaluated adult cardiac functional recovery during postischemic reperfusion and measured cardiac gene expression involved energy metabolism in rats neonatally treated with dexamethasone (DEX). METHOD: Male Wistar rats were injected DEX in first 3 d after birth and controls were received saline (SAL). At 24 wk of age, insulin tolerance tests were performed, plasma lipid levels were measured, and left ventricular function and myocardial infarct size were evaluated. Expressions of genes involved in cardiac energy metabolism were measured by quantitative real-time polymerase chain reaction (PCR) and western blot. RESULTS: In 24-wk-old rats, neonatal DEX administration caused dyslipidemia, impaired cardiac recovery function and increased size of infarction, decreased cardiac expression of glucose transporter 4(GLUT4), peroxisome proliferative-activated receptor gamma coactivator 1alpha (PGC-1alpha) and ratios of phospho-forkhead box O1/forkhead box O1 (p-FoxO1/FoxO1) and phospho AMP-activated protein kinase/AMP-activated protein kinase (p-AMPK/AMPK) but increased pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) expression compared with controls. CONCLUSION: Neonatal DEX administration impairs cardiac functional recovery during reperfusion following ischemia in 24-wk-old rats. Reduced cardiac glucose utilization may contribute to the long-term detrimental effects caused by neonatal DEX treatment. PMID- 26991266 TI - Myocardial strain can be measured from first trimester fetal echocardiography using velocity vector imaging. AB - OBJECTIVES: Alterations in myocardial strain can identify cardiac dysfunction and can be measured in the mid-gestation fetus. This study evaluates feasibility of strain measurements in early fetuses and establishes normal early fetal strain values. METHODS: Normal fetal echocardiograms were reviewed for image adequacy for strain measurements in 12- to 14-week gestation fetuses. Two readers performed independent strain measurements. Values were compared with data from 40 normal second trimester fetuses. RESULTS: Strain evaluation could be attempted in 36 of 53 (68%) of first trimester echocardiograms (mean gestation 13.4 weeks); excessive motion or inadequate imaging planes precluded tracking analysis in the remainder. Strain measurements were feasible in 19 of 53 fetuses (36%, or 53% of those in whom tracking was attempted). Peak systolic global longitudinal left ventricular (RV) and right ventricular (LV) strain were similar (LV = -13.9 +/- 5.7%, RV = -14.4 +/- 5.5%, p = 0.7). RV strain was higher in first trimester fetuses compared with second trimester normals (p = 0.003). Intraobserver and interobserver agreement were moderate to strong for peak global LV and RV strain but poor for regional basal and mid-septal segments. CONCLUSIONS: Strain measurements were feasible in one-third of retrospectively assessed early fetal echocardiograms. Global longitudinal strain may be higher in earlier than mid gestation fetuses. (c) 2016 John Wiley & Sons, Ltd. PMID- 26991265 TI - Microbiological characterization of a newly established pig breed, Aachen Minipigs. AB - BACKGROUND: To alleviate the shortage of human donor organs or tissues for the treatment of organ and tissue failure including diabetes, pigs are considered suitable donor animals. As organs from conventional pigs are usually too large, those from minipigs may be better suited. We recently characterized the Gottingen Minipigs, a breed well characterized concerning the presence of zoonotic microorganisms and found hepatitis E virus (HEV) and porcine cytomegalovirus (PCMV) in some animals. Here, we characterize another minipig, the Aachen Minipig (AaMP), a pig breed recently established close to the town Aachen in Germany. METHODS: The animals were tested for the prevalence and expression of porcine endogenous retroviruses (PERVs) and the presence of some selected microorganisms, among them HEV, PCMV, and porcine lymphotropic herpesviruses (PLHVs) using highly sensitive and specific PCR and RT-PCR methods. In addition, we screened for antibodies against HEV and PLHV. RESULTS: PERV-A, PERV-B, and PERV-C sequences were found in the genome of all Aachen Minipigs. HEV RNA was found by real-time RT-PCR in most, and DNA of PCMV, PLHV-2, and PLHV-3 was found by PCR in some animals. The animals were free of eight other microorganisms tested, but some were seropositive for porcine circovirus 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine epidemic diarrhea virus (PEDV). CONCLUSION: Based on medical examinations by veterinarians, the AaMP are in a good health status and seem to harbor only few microorganisms. To improve their status for use as donor pigs in xenotransplantation, the viruses detected might be eliminated by selection of negative animals, Cesarean section, and vaccination. PMID- 26991268 TI - Asymmetric Total Synthesis of Propindilactone G, Part 1: Initial Attempts towards the Synthesis of Schiartanes. AB - Our first-generation synthetic study towards the total synthesis of propindilactone G (1) and its analogues is reported. The key synthetic steps were an intramolecular Pauson-Khand reaction (PKR) and a vinylogous Mukaiyama reaction (VMAR). The stereoselective synthesis of the CDE ring moiety with an all-carbon quaternary center through a PKR was difficult, whilst a VMAR afforded a product with the opposite stereochemistry at the C20 position on the side chain. These results led us to redesign our synthetic strategy for the total synthesis of compound 1. PMID- 26991267 TI - Isolated Follicles Enriched for Centroblasts and Lacking t(14;18)/BCL2 in Lymphoid Tissue: Diagnostic and Clinical Implications. AB - We sought to address the significance of isolated follicles that exhibit atypical morphologic features that may be mistaken for lymphoma in a background of reactive lymphoid tissue. Seven cases that demonstrated centroblast-predominant isolated follicles and absent BCL2 staining in otherwise-normal lymph nodes were studied. Four of seven cases showed clonal B-cell proliferations amid a polyclonal B cell background; all cases lacked the IGH-BCL2 translocation and BCL2 protein expression. Although three patients had invasive breast carcinoma at other sites, none were associated with systemic lymphoma up to 44 months after diagnosis. The immunoarchitectural features of these highly unusual cases raise the question of whether a predominance of centroblasts and/or absence of BCL2 expression could represent a precursor lesion or atypical reactive phenomenon. Differentiating such cases from follicular lymphoma or another mimic is critical, lest patients with indolent proliferations be exposed to unnecessarily aggressive treatment. PMID- 26991269 TI - Correction: A Novel Rhabdovirus Associated with Acute Hemorrhagic Fever in Central Africa. PMID- 26991270 TI - Surface response methodology for the optimization of lipase production under submerged fermentation by filamentous fungi. AB - A Plackett-Burman Factorial Design of 16 experiments was conducted to assess the influence of nine factors on the production of lipases by filamentous fungi. The factors investigated were bran type (used as the main carbon source), nitrogen source, nitrogen source concentration, inducer, inducer concentration, fungal strain (Aspergillus niger or Aspergillus flavus were selected as good lipase producers via submerged fermentation), pH and agitation. The concentration of the yeast extract and soybean oil and the pH had a significant effect (p<0.05) on lipase production and were consecutively studied through a Full Factorial Design 2(3), with the concentration of yeast extract and pH being significant (p<0.05). These variables were optimized using a central composite design, obtaining maximum lipolytic activities with the use of 45g/L of yeast extract and pH 7.15. The statistical model showed a 94.12% correlation with the experimental data. PMID- 26991271 TI - Sphingomonas from petroleum-contaminated soils in Shenfu, China and their PAHs degradation abilities. AB - Members of the Sphingomonas genus are often isolated from petroleum-contaminated soils due to their unique abilities to degrade polycyclic aromatic hydrocarbons (PAHs), which are important for in situ bioremediation. In this study, a combined phenotypic and genotypic approach using streptomycin-containing medium and Sphingomonas-specific PCR was developed to isolate and identify culturable Sphingomonas strains present in petroleum-contaminated soils in the Shenfu wastewater irrigation zone. Of the 15 soil samples examined, 12 soils yielded yellow streptomycin-resistant colonies. The largest number of yellow colony forming units (CFUs) could reach 10(5)CFUsg(-1)soil. The number of yellow CFUs had a significant positive correlation (p<0.05) with the ratio of PAHs to total petroleum hydrocarbons (TPH), indicating that Sphingomonas may play a key role in degrading the PAH fraction of the petroleum contaminants at this site. Sixty yellow colonies were selected randomly and analyzed by colony PCR using Sphingomonas-specific primers, out of which 48 isolates had PCR-positive signals. The 48 positive amplicons generated 8 distinct restriction fragment length polymorphism (RFLP) patterns, and 7 out of 8 phylotypes were identified as Sphingomonas by 16S rRNA gene sequencing of the representative strains. Within these 7 Sphingomonas strains, 6 strains were capable of using fluorene as the sole carbon source, while 2 strains were phenanthrene-degrading Sphingomonas. To the best of our knowledge, this is the first report to evaluate the relationship between PAHs contamination levels and culturable Sphingomonas in environmental samples. PMID- 26991272 TI - Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for identification of Clostridium species isolated from Saudi Arabia. AB - The aim of this study was to identify different Clostridium spp. isolated from currency notes from the Ha'il region of Saudi Arabia in September 2014 using MALDI-TOF-MS. Clostridium spp. were identified by Bruker MALDI-TOF-MS and compared with VITEK 2. The confirmation of the presence of different Clostridium spp. was performed by determining the sequence of the 16S ribosomal RNA gene. In this study, 144 Clostridium spp. were isolated. Among these specimens, MALDI-TOF MS could identify 88.8% (128/144) of the isolates to the species level and 92.3% (133/144) to the genus level, whereas, VITEK 2 identified 77.7% of the (112/144) isolates. The correct identification of the 144 isolates was performed by sequence analysis of the 500bp 16S rRNA gene. The most common Clostridium spp. identified were Clostridium perfringens (67.36%), Clostridium subterminale (14.58%), Clostridium sordellii (9%) and Clostridium sporogenes (9%). The results of this study demonstrate that MALDI-TOF-MS is a rapid, accurate and user friendly technique for the identification of Clostridium spp. Additionally, MALDI TOF-MS has advantages over VITEK 2 in the identification of fastidious micro organisms, such as Clostridium spp. Incorporating this technique into routine microbiology would lead to more successful and rapid identification of pathogenic and difficult to identify micro-organisms. PMID- 26991273 TI - A protein expression system for tandem affinity purification in Xanthomonas citri subsp. citri. AB - Citrus canker, caused by the Gram-negative bacterium Xanthomonas citri subsp. citri (Xac), is one of the most devastating diseases to affect citrus crops. There is no treatment for citrus canker; effective control against the spread of Xac is usually achieved by the elimination of affected plants along with that of asymptomatic neighbors. An in depth understanding of the pathogen is the keystone for understanding of the disease; to this effect we are committed to the development of strategies to ease the study of Xac. Genome sequencing and annotation of Xac revealed that ~37% of the genome is composed of hypothetical ORFs. To start a systematic characterization of novel factors encoded by Xac, we constructed integrative-vectors for protein expression specific to this bacterium. The vectors allow for the production of TAP-tagged proteins in Xac under the regulation of the xylose promoter. In this study, we show that a TAP expression vector, integrated into the amy locus of Xac, does not compromise its virulence. Furthermore, our results also demonstrate that the polypeptide TAP can be overproduced in Xac and purified from the soluble phase of cell extracts. Our results substantiate the use of our vectors for protein expression in Xac thus contributing a novel tool for the characterization of proteins and protein complexes generated by this bacterium in vivo. PMID- 26991274 TI - Phylogenetic characterization of the first Ungulate tetraparvovirus 2 detected in pigs in Brazil. AB - Ungulate tetraparvovirus 2 (UTV2), formerly known as porcine hokovirus due to its discovery in Hong Kong, is closely related to a Primate tetraparvovirus (human PARV-4) and Ungulate tetraparvovirus 1 (bovine hokovirus). Until now, UTV2 was detected in European, Asian and North American countries, but its occurrence in Latin America is still unknown. This study describes the first report of UTV2 in Brazil, as well as its phylogenetic characterization. Tissue samples (lymph node, lung, liver, spleen and kidney) of 240 piglets from eight different herds (30 animals each herd) were processed for DNA extraction. UTV2 DNA was detected by PCR and the entire VP1/VP2 gene was sequenced for phylogenetic analysis. All pigs from this study displayed postweaning multisystemic wasting syndrome (PMWS). UTV2 was detected in 55.3% of the samples distributed in the variety of porcine tissues investigated, as well as detected in almost all herds, with one exception. The phylogenetic analysis demonstrated that Brazilian UTV2 sequences were more closely related to sequences from Europe and United States. PMID- 26991275 TI - Curli fimbria: an Escherichia coli adhesin associated with human cystitis. AB - Escherichia coli is the major causative agent of human cystitis. In this study, a preliminary molecular analysis carried out by PCR (polymerase chain reaction) demonstrated that 100% of 31 E. coli strains isolated from patients with recurrent UTIs (urinary tract infections) showed the presence of the curli fimbria gene (csgA). Curli fimbria is known to be associated with bacterial biofilm formation but not with the adhesion of human cystitis-associated E. coli. Therefore, this work aimed to study how curli fimbria is associated with uropathogenic E. coli (UPEC) as an adhesion factor. For this purpose, the csgA gene was deleted from strain UPEC-4, which carries three adhesion factor genes (csgA, fimH and ompA). The wild-type UPEC-4 strain and its mutant (DeltacsgA) were analyzed for their adhesion ability over HTB-9 (human bladder carcinoma), Vero (kidney cells of African green monkey) and HUVEC (human umbilical vein) cells in the presence of alpha-d-mannose. All the wild-type UPEC strains tested (100%) were able to adhere to all three cell types, while the UPEC-4 DeltacsgA mutant lost its adherence to HTB-9 but continued to adhere to the HUVEC and Vero cells. The results suggest that curli fimbria has an important role in the adhesion processes associated with human UPEC-induced cystitis. PMID- 26991276 TI - Occurrence and characteristics of extended spectrum beta-lactamases-producing Enterobacteriaceae from foods of animal origin. AB - Presence of extended spectrum beta-lactamases (ESBL) in bacteria is a growing health concern of global significance. The local, regional, national, and international epidemiological studies for extended spectrum beta-lactamases producing Enterobacteriaceae and their encoding genes in foods are still incomplete. The objective of this study was to determine the occurrence of extended spectrum beta-lactamases-producing Enterobacteriaceae and the characteristics of their encoding genes from a total of 250 samples of various foods of animal-origin (100 raw chicken meat, 100 raw cow milk, and 50 raw cow milk cheese) sold in Turkey. Overall, 55 isolates were positive as extended spectrum beta-lactamases-producing Enterobacteriaceae. The most prevalent extended spectrum beta-lactamases-producing strain were identified as Escherichia coli (80%), followed by Enterobacter cloacae (9.1%), Citrobacter braakii (5.5%), Klebsiella pneumoniae (3.6%), and Citrobacter werkmanii (1.8%) by Vitek((r)) MS. The simultaneous production of extended spectrum beta-lactamases and AmpC was detected in five isolates (9.1%) in E. coli (80%) and E. cloacae (20%). The frequency rates of blaTEM, blaCTX-M, and blaSHV were 96.4%, 53.7%, and 34.5%, respectively. The co-existence of bla-genes was observed in 82% of extended spectrum beta-lactamases producers with a distribution of blaTEM &blaCTX-M (52.7%), blaTEM &blaSHV (20%), blaTEM &blaCTX-M &blaSHV (12.7%), and blaSHV &blaCTX-M (1.8%). The most prevalent variant of blaCTX-M clusters was defined as blaCTX-M-1 (97.2%), followed by blaCTX-M-8 (2.8%). In summary, the analysed foods were found to be posing a health risk for Turkish consumers due to contamination by Enterobacteriaceae with a diversity of extended spectrum beta-lactamases encoding genes. PMID- 26991277 TI - Arbuscular mycorrhizal fungi in Mimosa tenuiflora (Willd.) Poir from Brazilian semi-arid. AB - Many plant species from Brazilian semi-arid present arbuscular mycorrhizal fungi (AMF) in their rhizosphere. These microorganisms play a key role in the establishment, growth, survival of plants and protection against drought, pathogenic fungi and nematodes. This study presents a quantitative analysis of the AMF species associated with Mimosa tenuiflora, an important native plant of the Caatinga flora. AMF diversity, spore abundance and root colonization were estimated in seven sampling locations in the Ceara and Paraiba States, during September of 2012. There were significant differences in soil properties, spore abundance, percentage of root colonization, and AMF diversity among sites. Altogether, 18 AMF species were identified, and spores of the genera Acaulospora, Claroideoglomus, Dentiscutata, Entrophospora, Funneliformis, Gigaspora, Glomus, Racocetra, Rhizoglomus and Scutellospora were observed. AMF species diversity and their spore abundance found in M. tenuiflora rhizosphere shown that this native plant species is an important host plant to AMF communities from Brazilian semi arid region. We concluded that: (a) during the dry period and in semi-arid conditions, there is a high spore production in M. tenuiflora root zone; and (b) soil properties, as soil pH and available phosphorous, affect AMF species diversity, thus constituting key factors for the similarity/dissimilarity of AMF communities in the M. tenuiflora root zone among sites. PMID- 26991278 TI - Cellulase activity and dissolved organic carbon release from lignocellulose macrophyte-derived in four trophic conditions. AB - Considering the importance of lignocellulose macrophyte-derived for the energy flux in aquatic ecosystems and the nutrient concentrations as a function of force which influences the decomposition process, this study aims to relate the enzymatic activity and lignocellulose hydrolysis in different trophic statuses. Water samples and two macrophyte species were collected from the littoral zone of a subtropical Brazilian Reservoir. A lignocellulosic matrix was obtained using aqueous extraction of dried plant material (~40 degrees C). Incubations for decomposition of the lignocellulosic matrix were prepared using lignocelluloses, inoculums and filtered water simulating different trophic statuses with the same N:P ratio. The particulate organic carbon and dissolved organic carbon (POC and DOC, respectively) were quantified, the cellulase enzymatic activity was measured by releasing reducing sugars and immobilized carbon was analyzed by filtration. During the cellulose degradation indicated by the cellulase activity, the dissolved organic carbon daily rate and enzyme activity increased. It was related to a fast hydrolysable fraction of cellulose that contributed to short-term carbon immobilization (ca. 10 days). After approximately 20 days, the dissolved organic carbon and enzyme activity were inversely correlated suggesting that the respiration of microorganisms was responsible for carbon mineralization. Cellulose was an important resource in low nutrient conditions (oligotrophic). However, the detritus quality played a major role in the lignocelluloses degradation (i.e., enzyme activity) and carbon release. PMID- 26991279 TI - Occurrence and antimicrobial resistance patterns of Listeria monocytogenes isolated from vegetables. AB - Although the consumption of fresh and minimally processed vegetables is considered healthy, outbreaks related to the contamination of these products are frequently reported. Among the food-borne pathogens that contaminate vegetables is Listeria monocytogenes, a ubiquitous organism that exhibits the ability to survive and multiply at refrigerated temperatures. This study aimed to evaluate the occurrence of L. monocytogenes in vegetables as well as the antimicrobial resistance of isolates. The results showed that 3.03% of samples were contaminated with L. monocytogenes, comprising 2.22% of raw vegetables and 5.56% of ready-to-eat vegetables. Multiplex PCR confirmed the virulence potential of the isolates. Antimicrobial resistance profiling showed that 50% of the isolates were susceptible to the antibiotics used. The resistance of one isolate to penicillin G, a commonly employed therapeutic agent, and the presence of serotype 4b, a serotype commonly associated with food-borne outbreaks, could be potential health hazards for consumers. PMID- 26991280 TI - Evaluation of a fungal collection as certified reference material producer and as a biological resource center. AB - Considering the absence of standards for culture collections and more specifically for biological resource centers in the world, in addition to the absence of certified biological material in Brazil, this study aimed to evaluate a Fungal Collection from Fiocruz, as a producer of certified reference material and as Biological Resource Center (BRC). For this evaluation, a checklist based on the requirements of ABNT ISO GUIA34:2012 correlated with the ABNT NBR ISO/IEC17025:2005, was designed and applied. Complementing the implementation of the checklist, an internal audit was performed. An evaluation of this Collection as a BRC was also conducted following the requirements of the NIT-DICLA-061, the Brazilian internal standard from Inmetro, based on ABNT NBR ISO/IEC 17025:2005, ABNT ISO GUIA 34:2012 and OECD Best Practice Guidelines for BRCs. This was the first time that the NIT DICLA-061 was applied in a culture collection during an internal audit. The assessments enabled the proposal for the adequacy of this Collection to assure the implementation of the management system for their future accreditation by Inmetro as a certified reference material producer as well as its future accreditation as a Biological Resource Center according to the NIT DICLA-061. PMID- 26991281 TI - Enhancement of pigment extraction from B. braunii pretreated using CO2 rapid depressurization. AB - Extraction of compounds from microalgae requires cell disruption as a pretreatment to increase extraction yield. Botryococcus braunii is a microalga with a significant content of carotenoids and other antioxidant compounds, such as chlorophylls. Cell disruption of B. braunii using CO2 rapid depressurization was studied as a pretreatment for the extraction of carotenoid and chlorophyll pigments. We studied the effect of temperature (21-49 degrees C) and pressure (6 13MPa) during static compression on pigment recovery with supercritical CO2 at 40 degrees C, 30MPa and solvent flow of 4.7LNPT/min. Within the experimental region, the extraction yield of carotenoids and chlorophylls increased by 2.4- and 2.2 fold respectively. Static compression conditions of high pressure and low temperature increased the extraction of carotenoids and especially chlorophylls. We selected 21 degrees C and 13MPa as the cell disruption condition, which produced 1.91g/kg d.s. of carotenoids and 14.03mg/kg d.s. of chlorophylls. Pretreated microalga gave a 10-fold higher chlorophyll extraction yield compared to the untreated sample. While for carotenoids and tocopherols were 1.25 and 1.14 fold higher, respectively. Additionally, antioxidant activity of pretreated microalga (33.22mmol TE/kg oil) was significantly higher than the value for the untreated samples (29.11mmol TE/kg oil) (p<=0.05). Confocal microscopy images showed morphological differences between micro-colonies with and without disruption treatment, suggesting that partial cell disruption by rapid depressurization improved the extraction of microalga compounds. PMID- 26991282 TI - Sugarcane straw as a feedstock for xylitol production by Candida guilliermondii FTI 20037. AB - Sugarcane straw has become an available lignocellulosic biomass since the progressive introduction of the non-burning harvest in Brazil. Besides keeping this biomass in the field, it can be used as a feedstock in thermochemical or biochemical conversion processes. This makes feasible its incorporation in a biorefinery, whose economic profitability could be supported by integrated production of low-value biofuels and high-value chemicals, e.g., xylitol, which has important industrial and clinical applications. Herein, biotechnological production of xylitol is presented as a possible route for the valorization of sugarcane straw and its incorporation in a biorefinery. Nutritional supplementation of the sugarcane straw hemicellulosic hydrolyzate as a function of initial oxygen availability was studied in batch fermentation of Candida guilliermondii FTI 20037. The nutritional supplementation conditions evaluated were: no supplementation; supplementation with (NH4)2SO4, and full supplementation with (NH4)2SO4, rice bran extract and CaCl2.2H2O. Experiments were performed at pH 5.5, 30 degrees C, 200rpm, for 48h in 125mL Erlenmeyer flasks containing either 25 or 50mL of medium in order to vary initial oxygen availability. Without supplementation, complete consumption of glucose and partial consumption of xylose were observed. In this condition the maximum xylitol yield (0.67gg(-1)) was obtained under reduced initial oxygen availability. Nutritional supplementation increased xylose consumption and xylitol production by up to 200% and 240%, respectively. The maximum xylitol volumetric productivity (0.34gL(-1)h(-1)) was reached at full supplementation and increased initial oxygen availability. The results demonstrated a combined effect of nutritional supplementation and initial oxygen availability on xylitol production from sugarcane straw hemicellulosic hydrolyzate. PMID- 26991283 TI - Proteobacteria, extremophiles and unassigned species dominate in a tape-like showerhead biofilm. AB - The development of showerhead biofilms exposes the user to repeated contact with potentially pathogenic microbes, yet we know relatively little about the content of these aggregates. The aim of the present study was to examine the microbial content of tape-like films found protruding from a domestic showerhead. Culturing showed that the films were dominated by aerobic alpha- and beta-proteobacteria. Three isolates made up almost the entire plate count. These were a Brevundimonas species, a metalophilic Cupriavidus species and a thermophile, Geobacillus species. Furthermore, it was shown that the Cupriavidus isolate alone had a high capacity for biofilm formation and thus might be the initiator of biofilm production. A clone library revealed the same general composition. However, half of the 70 clones analyzed could not be assigned to a particular bacterial phylum and of these 29 differed from one another by only 1-2 base pairs, indicating a single species. Thus both the culture dependent and culture independent characterizations suggest a simple yet novel composition. The work is important as the biofilm is fundamentally different in form (tape-like) and content from that of all previously reported ones, where variously Mycobacterium, Methylobacterium and Xanthomonas species have dominated, and extremophiles were not reported. PMID- 26991284 TI - Isolation of recombinant antibodies directed against surface proteins of Clostridium difficile. AB - Clostridium difficile has emerged as an increasingly important nosocomial pathogen and the prime causative agent of antibiotic-associated diarrhoea and pseudomembranous colitis in humans. In addition to toxins A and B, immunological studies using antisera from patients infected with C. difficile have shown that a number of other bacterial factors contribute to the pathogenesis, including surface proteins, which are responsible for adhesion, motility and other interactions with the human host. In this study, various clostridial targets, including FliC, FliD and cell wall protein 66, were expressed and purified. Phage antibody display yielded a large panel of specific recombinant antibodies, which were expressed, purified and characterised. Reactions of the recombinant antibodies with their targets were detected by enzyme-linked immunosorbent assay; and Western blotting suggested that linear rather than conformational epitopes were recognised. Binding of the recombinant antibodies to surface-layer proteins and their components showed strain specificity, with good recognition of proteins from C. difficile 630. However, no reaction was observed for strain R20291-a representative of the 027 ribotype. Binding of the recombinant antibodies to C. difficile M120 extracts indicated that a component of a surface-layer protein of this strain might possess immunoglobulin-binding activities. The recombinant antibodies against FliC and FliD proteins were able to inhibit bacterial motility. PMID- 26991285 TI - Bacteria isolated from Korean black raspberry vinegar with low biogenic amine production in wine. AB - A high concentration of histamine, one of the biogenic amines (BAs) usually found in fermented foods, can cause undesirable physiological side effects in sensitive humans. The objective of this study is to isolate indigenous Acetobacter strains from naturally fermented Bokbunja vinegar in Korea with reduced histamine production during starter fermentation. Further, we examined its physiological and biochemical properties, including BA synthesis. The obtained strain MBA-77, identified as Acetobacter aceti by 16S rDNA homology and biochemical analysis and named A. aceti MBA-77. A. aceti MBA-77 showed optimal acidity % production at pH 5; the optimal temperature was 25 degrees C. When we prepared and examined the BAs synthesis spectrum during the fermentation process, Bokbunja wine fermented with Saccharomyces cerevisiae showed that the histamine concentration increased from 2.72 of Bokbunja extract to 5.29mg/L and cadaverine and dopamine was decreased to 2.6 and 10.12mg/L, respectively. Bokbunja vinegar prepared by A. aceti MBA-77 as the starter, the histamine concentration of the vinegar preparation step was decreased up to 3.66mg/L from 5.29mg/L in the wine preparation step. To our knowledge, this is the first report to demonstrate acetic acid bacteria isolated from Bokbunja seed vinegar with low spectrum BA and would be useful for wellbeing vinegar preparation. PMID- 26991286 TI - Characterization of the variable region in the class 1 integron of antimicrobial resistant Escherichia coli isolated from surface water. AB - Fecal bacteria are considered to be a potential reservoir of antimicrobial resistance genes in the aquatic environment and could horizontally transfer these genes to autochthonous bacteria when carried on transferable and/or mobile genetic elements. Such circulation of resistance genes constitutes a latent public health hazard. The aim of this study was to characterize the variable region of the class 1 integron and relate its genetic content to resistance patterns observed in antimicrobial-resistant Escherichia coli isolated from the surface waters of Patos Lagoon, Southern Brazil. Genetic diversity of the isolates and presence of the qacEDelta1 gene, which confers resistance to quaternary ammonium compounds, were also investigated. A total of 27 isolates were analyzed. The variable region harbored dfrA17, dfrA1 and dfrA12 genes, which confer resistance to trimethoprim, and aadA1, aadA5 and aadA22 genes that encode resistance to streptomycin/spectinomycin. Most of the isolates were considered resistant to quaternary ammonium compounds and all of them carried the qacEDelta1 gene at the 3' conserved segment of the integron. ERIC-PCR analyses of E. coli isolates that presented the integrons showed great genetic diversity, indicating diverse sources of contamination in this environment. These results suggest that fecal bacteria with class 1 integrons in aquatic environments are potentially important reservoirs of antibiotic-resistance genes and may transfer these elements to other bacteria that are capable of infecting humans. PMID- 26991287 TI - DEFB1 gene polymorphisms and tuberculosis in a Northeastern Brazilian population. AB - beta-Defensin-1, an antimicrobial peptide encoded by the DEFB1 gene, is known to play an important role in lung mucosal immunity. In our association study we analyzed three DEFB1 functional polymorphisms -52G>A (rs1799946), -44C>G (rs1800972) and -20G>A (rs11362) in 92 tuberculosis patients and 286 healthy controls, both from Northeast Brazil: no association was found between the studied DEFB1 polymorphisms and the disease. However we cannot exclude that this lack of association could be due to the low number of subjects analyzed, as suggested by the low statistical power achieved for the three analyzed SNPs (values between 0.16 and 0.50). PMID- 26991288 TI - Effect of ultrasound on survival and growth of Escherichia coli in cactus pear juice during storage. AB - The aim of this study was to investigate the effectiveness of ultrasound as a conservation method for the inactivation of Escherichia coli inoculated into cactus pear juices (green and purple). Total soluble solids, pH, titratable acidity, and the kinetics of E. coli in cactus pear juices treated by ultrasound (60%, 70%, 80% and 90% amplitude levels for 1, 3 and 5min) were evaluated over 5 days. Total inactivation was observed in both fruit juices after 5min of ultrasound treatment at most amplitude levels (with the exception of 60% and 80%). After one and two days of storage, the recovery of bacteria counts was observed in all cactus pear juices. Ultrasound treatment at 90% amplitude for 5min resulted in non-detectable levels of E. coli in cactus pear juice for 2 days. The parameters of pH, titratable acidity and soluble solids were unaffected. PMID- 26991289 TI - Antimicrobial activities of six essential oils commonly used as condiments in Brazil against Clostridium perfringens. AB - Despite recent advances in food production technology, food-borne diseases (FBD) remain a challenging public health concern. In several countries, including Brazil, Clostridium perfringens is among the five main causative agents of food borne diseases. The present study determines antimicrobial activities of essential oils of six condiments commonly used in Brazil, viz., Ocimum basilicum L. (basil), Rosmarinus officinalis L. (rosemary), Origanum majorana L. (marjoram), Mentha * piperita L. var. Piperita (peppermint), Thymus vulgaris L. (thyme) and Pimpinella anisum L. (anise) against C. perfringens strain A. Chemical compositions of the oils were determined by GC-MS (gas chromatography mass spectrometry). The identities of the isolated compounds were established from the respective Kovats indices, and a comparison of mass spectral data was made with those reported earlier. The antibacterial activity was assessed from minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the microdilution method. Minimum inhibitory concentration values were 1.25mgmL(-1) for thyme, 5.0mgmL(-1) for basil and marjoram, and 10mgmL(-1) for rosemary, peppermint and anise. All oils showed bactericidal activity at their minimum inhibitory concentration, except anise oil, which was only bacteriostatic. The use of essential oils from these common spices might serve as an alternative to the use of chemical preservatives in the control and inactivation of pathogens in commercially produced food systems. PMID- 26991290 TI - Mycobacterium paratuberculosis detection in cow's milk in Argentina by immunomagnetic separation-PCR. AB - The aim of this study was to standardize a diagnosis procedure to detect Mycobacterium avium subsp. paratuberculosis (Map) DNA in raw cow milk samples under field conditions. A procedure that combines both immunomagnetic separation and IS900-PCR detection (IMS-IS1 PCR) was employed on milk samples from 265 lactating Holstein cows from Map infected and uninfected herds in Argentina. IMS IS1 PCR results were analyzed and compared with those obtained from milk and fecal culture and serum ELISA. The extent of agreement between both tests was determined by the Kappa test. IMS-IS1 PCR showed a detection limit of 10(1) CFU of Map/mL of milk, when 50:50 mix of monoclonal and polyclonal antibodies were used to coat magnetic beads. All of the 118 samples from the Map uninfected herds were negative for the set of the tests. In Map infected herds, 80 out of 147 cows tested positive by milk IMS-IS1 PCR (55%), of which 2 (1.4%) were also positive by milk culture, 15 (10%) by fecal culture, and 20 (14%) by serum ELISA. Kappa statistics (95% CI) showed a slight agreement between the different tests (<0.20), and the proportions of agreement were <=0.55. The IMS-IS1 PCR method detected Map in milk of the cows that were not positive in other techniques. This is the first report dealing with the application of IMS-IS1 PCR in the detection of Map in raw milk samples under field conditions in Argentina. PMID- 26991291 TI - Detection of carboxylesterase and esterase activity in culturable gut bacterial flora isolated from diamondback moth, Plutella xylostella (Linnaeus), from India and its possible role in indoxacarb degradation. AB - Diamondback moth (DBM), Plutella xylostella (Linnaeus), is a notorious pest of brassica crops worldwide and is resistant to all groups of insecticides. The insect system harbors diverse groups of microbiota, which in turn helps in enzymatic degradation of xenobiotic-like insecticides. The present study aimed to determine the diversity of gut microflora in DBM, quantify esterase activity and elucidate their possible role in degradation of indoxacarb. We screened 11 geographic populations of DBM in India and analyzed them for bacterial diversity. The culturable gut bacterial flora underwent molecular characterization with 16S rRNA. We obtained 25 bacterial isolates from larvae (n=13) and adults (n=12) of DBM. In larval gut isolates, gammaproteobacteria was the most abundant (76%), followed by bacilli (15.4%). Molecular characterization placed adult gut bacterial strains into three major classes based on abundance: gammaproteobacteria (66%), bacilli (16.7%) and flavobacteria (16.7%). Esterase activity from 19 gut bacterial isolates ranged from 0.072 to 2.32MUmol/min/mg protein. Esterase bands were observed in 15 bacterial strains and the banding pattern differed in Bacillus cereus - KC985225 and Pantoea agglomerans - KC985229. The bands were characterized as carboxylesterase with profenofos used as an inhibitor. Minimal media study showed that B. cereus degraded indoxacarb up to 20%, so it could use indoxacarb for metabolism and growth. Furthermore, esterase activity was greater with minimal media than control media: 1.87 versus 0.26MUmol/min/mg protein. Apart from the insect esterases, bacterial carboxylesterase may aid in the degradation of insecticides in DBM. PMID- 26991292 TI - Enhanced production of erythritol and mannitol by Yarrowia lipolytica in media containing surfactants. AB - Various chemical compounds, including surfactants, when introduced to culture media may increase the permeability of cellular membranes and thereby affect the quantity of metabolites excreted by cells. The aim of the present study was to evaluate the impact of detergents including Triton X-100, Span 20 and Tween 80 on erythritol production from glycerol by Yarrowia lipolytica Wratislavia K1 in a shake-flask experiment, batch and fed-batch cultures. When Span 20 was added to a fed-batch culture with glycerol as a carbon source (300gL(-1)), erythritol production increased by 15% compared to the culture without the surfactant where it reached 142gL(-1) after 5 days, which corresponded to 0.47gg(-1) yield and productivity of 1.1gL(-1)h(-1). Therefore, it was concluded that Span 20 considerably enhanced the production of this polyol from glycerol. PMID- 26991293 TI - Sugarcane trash levels in soil affects the fungi but not bacteria in a short-term field experiment. AB - The sugarcane in Brazil is passing through a management transition that is leading to the abolition of pre-harvest burning. Without burning, large amounts of sugarcane trash is generated, and there is a discussion regarding the utilization of this biomass in the industry versus keeping it in the field to improve soil quality. To study the effects of the trash removal on soil quality, we established an experimental sugarcane plantation with different levels of trash over the soil (0%, 50% and 100% of the original trash deposition) and analyzed the structure of the bacterial and fungal community as the bioindicators of impacts. The soil DNA was extracted, and the microbial community was screened by denaturing gradient gel electrophoresis in two different seasons. Our results suggest that there are no effects from the different levels of trash on the soil chemistry and soil bacterial community. However, the fungal community was significantly impacted, and after twelve months, the community presented different structures among the treatments. PMID- 26991294 TI - Rhizobial characterization in revegetated areas after bauxite mining. AB - Little is known regarding how the increased diversity of nitrogen-fixing bacteria contributes to the productivity and diversity of plants in complex communities. However, some authors have shown that the presence of a diverse group of nodulating bacteria is required for different plant species to coexist. A better understanding of the plant symbiotic organism diversity role in natural ecosystems can be extremely useful to define recovery strategies of environments that were degraded by human activities. This study used ARDRA, BOX-PCR fingerprinting and sequencing of the 16S rDNA gene to assess the diversity of root nodule nitrogen-fixing bacteria in former bauxite mining areas that were replanted in 1981, 1985, 1993, 1998, 2004 and 2006 and in a native forest. Among the 12 isolates for which the 16S rDNA gene was partially sequenced, eight, three and one isolate(s) presented similarity with sequences of the genera Bradyrhizobium, Rhizobium and Mesorhizobium, respectively. The richness, Shannon and evenness indices were the highest in the area that was replanted the earliest (1981) and the lowest in the area that was replanted most recently (2006). PMID- 26991295 TI - Screening of Trichoderma isolates for their potential of biosorption of nickel and cadmium. AB - Fourteen Trichoderma isolates were evaluated for their tolerance to two heavy metals, nickel and cadmium. Three isolates, MT-4, UBT-18, and IBT-I, showed high levels of nickel tolerance, whereas MT-4, UBT-18, and IBT-II showed better tolerance of cadmium than the other isolates. Under nickel stress, biomass production increased up to a Ni concentration of 60ppm in all strains but then decreased as the concentrations of nickel were further increased. Among the nickel-tolerant isolates, UBT-18 produced significantly higher biomass upon exposure to nickel (up to 150ppm); however, the minimum concentration of nickel required to inhibit 50% of growth (MIC50) was highest in IBT-I. Among the cadmium tolerant isolates, IBT-II showed both maximum biomass production and a maximum MIC50 value in cadmium stress. As the biomass of the Trichoderma isolates increased, a higher percentage of nickel removal was observed up to a concentration of 40ppm, followed by an increase in residual nickel and a decrease in biomass production at higher nickel concentrations in the medium. The increase in cadmium concentrations resulted in a decrease in biomass production and positively correlated with an increase in residual cadmium in the culture broth. Nickel and cadmium stress also influenced the sensitivity of the Trichoderma isolates to soil fungistasis. Isolates IBT-I and UBT-18 were most tolerant to fungistasis under nickel and cadmium stress, respectively. PMID- 26991296 TI - Membrane permeabilization of colistin toward pan-drug resistant Gram-negative isolates. AB - Pan-drug resistant Gram-negative bacteria, being resistant to most available antibiotics, represent a huge threat to the medical community. Colistin is considered the last therapeutic option for patients in hospital settings. Thus, we were concerned in this study to demonstrate the membrane permeabilizing activity of colistin focusing on investigating its efficiency toward those pan drug resistant isolates which represent a critical situation. We determined the killing dynamics of colistin against pan-drug resistant isolates. The permeability alteration was confirmed by different techniques as: leakage, electron microscopy and construction of an artificial membrane model; liposomes. Moreover, selectivity of colistin against microbial cells was also elucidated. Colistin was proved to be rapid bactericidal against pan-drug resistant isolates. It interacts with the outer bacterial membrane leading to deformation of its outline, pore formation, leakage of internal contents, cell lysis and finally death. Furthermore, variations in membrane composition of eukaryotic and microbial cells provide a key for colistin selectivity toward bacterial cells. Colistin selectively alters membrane permeability of pan-drug resistant isolates which leads to cell lysis. Colistin was proved to be an efficient last line treatment for pan-drug resistant infections which are hard to treat. PMID- 26991297 TI - Endophytic fungus strain 28 isolated from Houttuynia cordata possesses wide spectrum antifungal activity. AB - The aim of this paper is to identify and investigate an endophytic fungus (strain 28) that was isolated from Houttuynia cordata Thunb, a famous and widely-used Traditional Chinese Medicine. Based on morphological methods and a phylogenetic analysis of ITS sequences, this strain was identified as Chaetomium globosum. An antifungal activity bioassay demonstrated that the crude ethyl acetate (EtOAc) extracts of strain 28 had a wide antifungal spectrum and strong antimicrobial activity, particularly against Exserohilum turcicum (Pass.) Leonard et Suggs, Botrytis cinerea persoon and Botrytis cinerea Pers. ex Fr. Furthermore, the fermentation conditions, extraction method and the heat stability of antifungal substances from strain 28 were also studied. The results showed that optimal antifungal activity can be obtained with the following parameters: using potato dextrose broth (PDB) as the base culture medium, fermentation for 4-8d (initial pH: 7.5), followed by extraction with EtOAc. The extract was stable at temperatures up to 80 degrees C. This is the first report on the isolation of endophytic C. globosum from H. cordata to identify potential alternative biocontrol agents that could provide new opportunities for practical applications involving H. cordata. PMID- 26991298 TI - Susceptibility and molecular characterization of Candida species from patients with vulvovaginitis. AB - Vulvovaginal candidiasis affects women of reproductive age, which represents approximately 15-25% of vaginitis cases. The present study aimed to isolate and characterize yeast from the patients irrespective of the presentation of clinical symptoms. The isolates were subjected to in vitro susceptibility profile and characterization by molecular markers, which intended to assess the distribution of species. A total of 40 isolates were obtained and identified through the CHROMagar, API20aux and by ITS and D1/D2 regions sequencing of DNAr gene. Candida albicans strains were genotyped by the ABC system and the isolates were divided into two genotypic groups. The identity of the C. albicans, C. glabrata, C. guilliermondii, C. kefyr and Saccharomyces cerevisiae isolates was confirmed by the multilocus analysis. The strains of Candida, isolated from patients with complications, were found to be resistant to nystatin but sensitive to fluconazole, amphotericin B and ketoconazole, as observed by in vitro sensitivity profile. The isolates from asymptomatic patients, i.e., the colonized group, showed a dose-dependent sensitivity to the anti-fungal agents, fluconazole and amphotericin B. However, the isolates of C. albicans that belong to distinct genotypic groups showed the same in vitro susceptibility profile. PMID- 26991299 TI - Isolation and expression of two polyketide synthase genes from Trichoderma harzianum 88 during mycoparasitism. AB - Metabolites of mycoparasitic fungal species such as Trichoderma harzianum 88 have important biological roles. In this study, two new ketoacyl synthase (KS) fragments were isolated from cultured Trichoderma harzianum 88 mycelia using degenerate primers and analysed using a phylogenetic tree. The gene fragments were determined to be present as single copies in Trichoderma harzianum 88 through southern blot analysis using digoxigenin-labelled KS gene fragments as probes. The complete sequence analysis in formation of pksT-1 (5669bp) and pksT-2 (7901bp) suggests that pksT-1 exhibited features of a non-reducing type I fungal PKS, whereas pksT-2 exhibited features of a highly reducing type I fungal PKS. Reverse transcription polymerase chain reaction indicated that the isolated genes are differentially regulated in Trichoderma harzianum 88 during challenge with three fungal plant pathogens, which suggests that they participate in the response of Trichoderma harzianum 88 to fungal plant pathogens. Furthermore, disruption of the pksT-2 encoding ketosynthase-acyltransferase domains through Agrobacterium-mediated gene transformation indicated that pksT-2 is a key factor for conidial pigmentation in Trichoderma harzianum 88. PMID- 26991300 TI - Role of pH on antioxidants production by Spirulina (Arthrospira) platensis. AB - Algae can tolerate a broad range of growing conditions but extreme conditions may lead to the generation of highly dangerous reactive oxygen species (ROS), which may cause the deterioration of cell metabolism and damage cellular components. The antioxidants produced by algae alleviate the harmful effects of ROS. While the enhancement of antioxidant production in blue green algae under stress has been reported, the antioxidant response to changes in pH levels requires further investigation. This study presents the effect of pH changes on the antioxidant activity and productivity of the blue green alga Spirulina (Arthrospira) platensis. The algal dry weight (DW) was greatly enhanced at pH 9.0. The highest content of chlorophyll a and carotenoids (10.6 and 2.4mg/g DW, respectively) was recorded at pH 8.5. The highest phenolic content (12.1mg gallic acid equivalent (GAE)/g DW) was recorded at pH 9.5. The maximum production of total phycobiliprotein (159mg/g DW) was obtained at pH 9.0. The antioxidant activities of radical scavenging activity, reducing power and chelating activity were highest at pH 9.0 with an increase of 567, 250 and 206% compared to the positive control, respectively. Variation in the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) was also reported. While the high alkaline pH may favor the overproduction of antioxidants, normal cell metabolism and membrane function is unaffected, as shown by growth and chlorophyll content, which suggests that these conditions are suitable for further studies on the harvest of antioxidants from S. platensis. PMID- 26991301 TI - Preliminary studies of new strains of Trametes sp. from Argentina for laccase production ability. AB - Oxidative enzymes secreted by white rot fungi can be applied in several technological processes within the paper industry, biofuel production and bioremediation. The discovery of native strains from the biodiverse Misiones (Argentina) forest can provide useful enzymes for biotechnological purposes. In this work, we evaluated the laccase and manganese peroxidase secretion abilities of four newly discovered strains of Trametes sp. that are native to Misiones. In addition, the copper response and optimal pH and temperature for laccase activity in culture supernatants were determined. The selected strains produced variable amounts of laccase and MnP; when Cu(2+) was added, both enzymes were significantly increased. Zymograms showed that two isoenzymes were increased in all strains in the presence of Cu(2+). Strain B showed the greatest response to Cu(2+) addition, whereas strain A was more stable at the optimal temperature and pH. Strain A showed interesting potential for future biotechnological approaches due to the superior thermo-stability of its secreted enzymes. PMID- 26991302 TI - Candida glabrata among Candida spp. from environmental health practitioners of a Brazilian Hospital. AB - The incidence of the species Candida albicans and non-albicans Candida was evaluated in a Brazilian Tertiary Hospital from the environment and health practitioners. In a 12-month period we had a total positivity of 19.65% of Candida spp. The most recurring non-albicans Candida species was C. glabrata (37.62%), generally considered a species of low virulence, but with a higher mortality rate than C. albicans. Subsequently, C. parapsilosis (25.74%) and C. tropicalis (16.86%) were the second and third most commonly isolated species. Considering the total samples collected from the emergency room and from the inpatient and the pediatric sector, 19.10% were positive for Candida spp., with the predominance of non-albicans Candida species (89.42%). The high percentage of positivity occurred in the hands (24.32%) and the lab coats (21.88%) of the health care assistants. No sample of C. albicans presented a profile of resistance to the drugs. All the non-albicans Candida species presented a decreased susceptibility to miconazole and itraconazole, but they were susceptible to nystatin. Most of the isolates were susceptible to fluconazole and amphotericin B. As expected, a high resistance rate was observed in C. glabrata and C. krusei, which are intrinsically less susceptible to this antifungal agent. The contamination of environmental surfaces by Candida spp. through hand touching may facilitate the occurrence of Candida infections predominantly in immunocompromised patients. In addition to that, the antifungal agents used should be carefully evaluated considering local epidemiologic trends in Candida spp. infections, so that therapeutic choices may be better guided. PMID- 26991303 TI - Eichhornia azurea decomposition and the bacterial dynamic: an experimental research. AB - Organic decomposition is a complex interaction between chemical, physical and biological processes, where the variety of aquatic vascular plants is essential for the trophic dynamics of freshwater ecosystems. The goal of this study was to determine the aquatic macrophyte Eichhornia azurea (Sw.) Kunth decomposition rate, the time relation with the limnological parameters, and whether this relationship is a result of decomposition processes. To that end, we collected water and leaves of E. azurea in Surf Leopoldo, PR. The experiment consisted of two treatments: 25 containers with 450mL of water and 0.8g of biomass dry weight were used with or without the addition of macrophytes. Samples were collected in triplicate at times 0, 3h, 6h, 12h, 24h, 72h, 120h, 168h and 240h. When the container was removed, the plant material was dried in an oven. After 48h, the material was measured to obtain the final dry weight. Analyses of pH, conductivity, dissolved oxygen, total phosphorus N-ammonia (NH4), soluble reactive phosphorus (PO4) and dissolved organic carbon were performed, and the decomposition rate was calculated. The results showed significant temporal variation of limnological parameters in the study. Additionally, dissolved oxygen, conductivity, dissolved organic carbon and total phosphorus were correlated with the dry weight of the biomass, suggesting that E. azurea decomposition significantly interferes with the dynamics of these variables. PMID- 26991304 TI - Draft genome sequence of a caprolactam degrader bacterium: Pseudomonas taiwanensis strain SJ9. AB - Pseudomonas taiwanensis strain SJ9 is a caprolactam degrader, isolated from industrial wastewater in South Korea and considered to have the potential for caprolactam bioremediation. The genome of this strain is approximately 6.2 Mb (G+C content, 61.75%) with 6,010 protein-coding sequences (CDS), of which 46% are assigned to recognized functional genes. This draft genome of strain SJ9 will provide insights into the genetic basis of its caprolactam-degradation ability. PMID- 26991305 TI - Risk Factors for Hyperglycaemia in Pregnancy in Tamil Nadu, India. AB - INTRODUCTION: Hyperglycaemia in pregnancy (HIP), i.e. gestational diabetes mellitus (GDM) and diabetes in pregnancy (DIP), increases the risk of various short- and long-term adverse outcomes. However, much remains to be understood about the role of different risk factors in development of HIP. OBJECTIVE: The aims of this observational study were to examine the role of potential risk factors for HIP, and to investigate whether any single or accumulated risk factor(s) could be used to predict HIP among women attending GDM screening at three centres in urban, semi-urban and rural Tamil Nadu, India. METHODOLOGY: Pregnant women underwent a 75 g oral glucose tolerance test. Data on potential risk factors was collected and analysed using logistical regression analysis. Receiver operating characteristic (ROC) curves, sensitivity, specificity and predictive values were calculated for significant risk factors and a risk factor scoring variable was constructed. RESULTS: HIP was prevalent in 18.9% of the study population (16.3% GDM; 2.6% DIP). Increasing age and BMI as well as having a mother only or both parents with diabetes were significant independent risk factors for HIP. Among women attending the rural health centre a doubling of income corresponded to an 80% increased risk of HIP (OR 1.80, 95%CI 1.10-2.93; p = 0.019), whereas it was not significantly associated with HIP among women attending the other health centres. The performance of the individual risk factors and the constructed scoring variable differed substantially between the three health centres, but none of them were good enough to discriminate between those with and without HIP. CONCLUSIONS: The findings highlight the importance of socio-economic circumstances and intergenerational risk transmission in the occurrence of HIP as well as the need for universal screening. PMID- 26991306 TI - Catalytic Water Oxidation by Ruthenium Complexes Containing Negatively Charged Ligand Frameworks. AB - Artificial photosynthesis represents an attractive way of converting solar energy into storable chemical energy. The H2O oxidation half-reaction, which is essential for producing the necessary reduction equivalents, is an energy demanding transformation associated with a high kinetic barrier. Herein we present a couple of efficient Ru-based catalysts capable of mediating this four proton-four-electron oxidation. We have focused on the incorporation of negatively charged ligands, such as carboxylate, phenol, and imidazole, into the catalysts to decrease the redox potentials. This account describes our work in designing Ru catalysts based on this idea. The presence of the negatively charged ligands is crucial for stabilizing the metal centers, allowing for light-driven H2O oxidation. Mechanistic details associated with the designed catalysts are also presented. PMID- 26991307 TI - Hormone responsiveness of cultured Sertoli cells obtained from adult rats after their rapid isolation under less harsh conditions. AB - During adulthood, testicular Sertoli cells (Sc) coordinate all stages of germ cell (Gc) development involved in sperm production. However, our understanding about the functions of adult Sc is limited because of the difficulties involved in the process of isolating these cells from the adult testis, mainly because of the presence of large number of advanced Gc which interfere with Sc isolation at this age. Most of our knowledge about Sc function are derived from studies which used pre-pubertal rat Sc (18 +/- 2-day old) as it is easy to isolate and culture Sc at this age. To this end, we established a less time consuming and less harsh procedure of isolating Sc from adult (60 days of age) rat testis for facilitating research on Sc-mediated regulation of spermatogenesis during adulthood. The cells were isolated using collagenase digestion at higher temperature, reducing the exposure time of cells to the enzyme. Step-wise digestion with intermittent removal of small clusters of tissue helped in increasing the yield of Sc. Isolated Sc were cultured and treated with FSH and testosterone (T) to evaluate their hormone responsiveness in terms of lactate, E2 , cAMP production. Adult Sc were found to be active and produced high amounts of lactate in a FSH-independent manner. FSH-mediated augmentation of cAMP and E2 production by adult Sc was less as compared with that by pre-pubertal Sc obtained from 18-day-old rats. Androgen binding ability of adult Sc was significantly higher than pre-pubertal Sc. Although T treatment remarkably augmented expression of Claudin 11, it failed to augment lactate production by adult Sc. This efficient and rapid procedure for isolation and culture of functionally viable adult rat Sertoli cells may pave the way for determining their role in regulation and maintenance of spermatogenesis. PMID- 26991308 TI - Neighbourhood Walkability and Daily Steps in Adults with Type 2 Diabetes. AB - INTRODUCTION: There is evidence that greater neighbourhood walkability (i.e., neighbourhoods with more amenities and well-connected streets) is associated with higher levels of total walking in Europe and in Asia, but it remains unclear if this association holds in the Canadian context and in chronic disease populations. We examined the relationships of different walkability measures to biosensor-assessed total walking (i.e., steps/day) in adults with type 2 diabetes living in Montreal (QC, Canada). MATERIALS AND METHODS: Participants (60.5+/-10.4 years; 48.1% women) were recruited through McGill University-affiliated clinics (June 2006 to May 2008). Steps/day were assessed once per season for one year with pedometers. Neighbourhood walkability was evaluated through participant reports, in-field audits, Geographic Information Systems (GIS)-derived measures, and the Walk Score(r). Relationships between walkability and daily steps were estimated using Bayesian longitudinal hierarchical linear regression models (n = 131). RESULTS: Participants who reported living in the most compared to the least walkable neighbourhoods completed 1345 more steps/day (95% Credible Interval: 718, 1976; Quartiles 4 versus 1). Those living in the most compared to the least walkable neighbourhoods (based on GIS-derived walkability) completed 606 more steps per day (95% CrI: 8, 1203). No statistically significant associations with steps were observed for audit-assessed walkability or the Walk Score(r). CONCLUSIONS: Adults with type 2 diabetes who perceived their neighbourhoods as more walkable accumulated more daily steps. This suggests that knowledge of local neighborhood features that enhance walking is a meaningful predictor of higher levels of walking and an important component of neighbourhood walkability. PMID- 26991309 TI - A three-dimensional cell culture system as an in vitro canine mammary carcinoma model for the expression of connective tissue modulators. AB - In this study, derived complex carcinoma (CC) and simple carcinoma (SC) cell lines were established and cultured under two-dimensional (2D) and three dimensional (3D) conditions. The 3D was performed in six-well AlgiMatrixTM (LifeTechnologies(r), Carlsbad, CA, USA) scaffolds, resulting in spheroids sized 50-125 um for CC and 175-200 um for SC. Cell viability was demonstrated up to 14 days for both models. Epidermal growth factor receptor (EGFR) was expressed in CC and SC in both systems. However, higher mRNA and protein levels were observed in SC 2D and 3D systems when compared with CC (P < 0.005). The connective tissue modulators, metalloproteinases-1, -2, -9 and -13 (MMPs), relaxin receptors 1 and 2 (RXR1 and RXR2) and E-cadherin (CDH1) were quantitated. All were upregulated similarly when canine mammary tumour (CMT)-derived cell lines were cultured under 3D AlgiMatrix, except CDH1 that was downregulated (P < 0.005). These results are promising towards the used of 3D system to increase a high throughput in vitro canine tumour model. PMID- 26991310 TI - Stabilization of 3d Transition Metal Hydrido Complexes in SrH2Mg2[Co(I)H5], BaH2Mg5[Co(-I)H4]2, and RbH2Mg5[Co(-I)H4 Ni(0)H4] via Easily Polarizable Hydride Ligands. AB - A combined study using neutron diffraction, inelastic neutron scattering, and first-principles calculations describe cobalt with a very low formal oxidation state of (-I) in a slightly distorted tetrahedral Co(-I)H4-complex in BaH2Mg5[Co( I)H4]2 and in the structurally related RbH2Mg5[Co(-I)H4 Ni(0)H4]. This indicates that the electron "back donating" effect via the polarizable hydride ions to the counterions in the solid state hydrides, can be compared to more conventional "back bonding" able to reduce the oxidation state down to -I. The hydrides were synthesized by hot sintering of transition metal powders with corresponding binary alkali- and alkaline earth hydrides. In the similarly synthesized SrH2Mg2[Co(I)H5], cobalt is formally + I-valent, showing a high sensitivity to differences in the counterion framework, which can also influence electrical properties. PMID- 26991311 TI - Use of a novel statistical technique to examine the delivery of breast cancer follow-up care by different types of oncology providers. AB - RATIONALE, AIMS AND OBJECTIVES: Frequent follow-up is recommended for the more than 3 million breast cancer survivors living in the USA. Given the multidisciplinary nature of breast cancer treatment, follow-up may be provided by medical oncologists, radiation oncologists, surgeons and primary care providers. This creates the potential for significant redundancy as well as gaps in care. The objective was to examine patterns of breast cancer follow-up provided by different types of oncologists and develop a statistical means of quantifying visit distribution over time. METHODS: We identified stage I-III breast cancer patients who underwent breast conservation from 2000 to 2006 (n = 12 139) within the SEER-Medicare linked database. Provider type was defined using Medicare specialty provider codes and AMA Masterfile. The coefficient of variation (CV) for time between oncologist follow-up visits was calculated. Ordinal logistic regression assessed factors associated with CV. RESULTS: Substantial variation in CV was observed. Sixty-seven per cent of patients with low CV (high visit regularity) received follow-up from a single oncologist type, versus 8% with high CV (low visit regularity). The number of oncologist types participating in follow up had the greatest association with high CV (odds ratio 7.4 [6.7-8.3] and 15.4 [13.6-17.6] for two and three oncologist types). CONCLUSIONS: Using a novel means of quantifying follow-up visit regularity, we determined that breast cancer patients with dispersed follow-up with more than one oncologist have more disordered care. The CV could be used in electronic medical records to identify cancer survivors with more disordered. PMID- 26991312 TI - Incisional negative pressure wound therapy in reconstructive surgery of poststernotomy mediastinitis. AB - The efficacy of negative pressure wound therapy in the treatment of poststernotomy mediastinitis has been revealed in many reports. The present retrospective observational study examined the efficacy of incisional negative pressure wound therapy in the reconstructive surgery of poststernotomy mediastinitis. We retrospectively examined 1034 consecutive patients, who underwent median sternotomy in the period between October 2013 and September 2015. Mediastinitis developed in 21 patients (2%), who subsequently underwent surgical reconstruction. We applied incisional negative pressure wound therapy (iNPWT) after primary closure of the wound over redon drains in ten patients (iNPWT + redon group). In 11 patients, only redons were used (redons only group). We observed the time between the introduction and removal of redon drains, hospital stay until final wound closure and the rate of failure of treatment. Failure of treatment is defined as the need for further surgical reconstruction. In the iNPWT + redon group, the duration of redon drainage therapy was 6.9 +/- 5.2 days versus 13.36 +/- 11.58 in the redons only group. Hospital stay was 11.4 +/- 8.6 versus 101.64 +/- 89.2, and failure of treatment was 10% versus 45.5%, respectively. The primary results of this study appear to support the beneficial effect of iNPWT after radical wound reconstruction. PMID- 26991314 TI - Superior Vena Cava Obstruction in Hemodialysis Patients: Symptoms, Clinical Presentation and Outcomes Compared to Other Etiologies. AB - The incidence of superior vena cava (SVC) obstruction associated with non malignant diseases is on the rise, and a large percentage of these patients are on hemodialysis (HD). The objective was to characterize the presentation, symptoms and outcomes of HD patients with SVC obstruction identified on computerized tomography (CT) compared to patients with other etiologies such as neoplasm. A search was performed through the PACS system using key words to identify patients with SVC obstruction. The CT scans and charts were reviewed for degree of obstruction, signs, symptoms and outcomes. Thirty-six patients were included in the study. Thirteen were on HD and of these, five had symptoms associated with SVC obstruction and one had concordant findings on physical exam. In comparison, thirteen patients with a chest neoplasm had symptoms and four had concordant findings on physical exam. On follow up, 31% of the HD patients died and of these 60% were symptomatic and died within 2 years. 29% of lung cancer patients died within 16 months. The majority of the HD patients had complete SVC obstruction (85%) as opposed to those with a chest neoplasm who mostly had partial SVC occlusion (67%). In conclusion, patients on HD with SVC obstruction are less often symptomatic than those with a neoplasm. However, these HD patients had a death rate similar to the patients with cancer. This risk seems to increase in those who are symptomatic. Diagnosis of SVC obstruction by CT in HD patients may help identify those with less favorable prognosis. PMID- 26991313 TI - Vital and dispensable roles of Plasmodium multidrug resistance transporters during blood- and mosquito-stage development. AB - Multidrug resistance (MDR) proteins belong to the B subfamily of the ATP Binding Cassette (ABC) transporters, which export a wide range of compounds including pharmaceuticals. In this study, we used reverse genetics to study the role of all seven Plasmodium MDR proteins during the life cycle of malaria parasites. Four P. berghei genes (encoding MDR1, 4, 6 and 7) were refractory to deletion, indicating a vital role during blood stage multiplication and validating them as potential targets for antimalarial drugs. Mutants lacking expression of MDR2, MDR3 and MDR5 were generated in both P. berghei and P. falciparum, indicating a dispensable role for blood stage development. Whereas P. berghei mutants lacking MDR3 and MDR5 had a reduced blood stage multiplication in vivo, blood stage growth of P. falciparum mutants in vitro was not significantly different. Oocyst maturation and sporozoite formation in Plasmodium mutants lacking MDR2 or MDR5 was reduced. Sporozoites of these P. berghei mutants were capable of infecting mice and life cycle completion, indicating the absence of vital roles during liver stage development. Our results demonstrate vital and dispensable roles of MDR proteins during blood stages and an important function in sporogony for MDR2 and MDR5 in both Plasmodium species. PMID- 26991316 TI - Intact neural activity during a Go/No-go task is associated with high global functioning in schizophrenia. AB - AIM: Go/No-go derived event-related potential (ERP) signals have been widely used in schizophrenia research to monitor self-control deficits in this disorder. However, no study to date has associated Go/No-go-related ERP with global functioning. METHODS: Participants consisted of 21 patients with schizophrenia and 22 healthy controls. We used a visual Go/No-go paradigm to measure Go/No-go related N2/P3 ERP components by means of a 64-electrode cap for electroencephalogram recording. We used the Global Assessment of Functioning to evaluate global functioning and analyzed the correlation between ERP indices and global functioning scores. RESULTS: N2 amplitudes were reduced in patients with schizophrenia, but not influenced by either of the Go/No-go conditions. P3 amplitudes were influenced by the Go/No-go conditions, but not reduced in patients with schizophrenia. Global functioning was correlated with the No-go P3 amplitudes, but not N2 amplitudes, in patients with schizophrenia. CONCLUSION: These results indicate that global functioning is associated with intact neural activity rather than impaired neural activity during Go/No-go response inhibition tasks in patients with schizophrenia. PMID- 26991317 TI - A systematic review of the association between depression and health care utilization in children and adults with sickle cell disease. AB - Patients with sickle cell disease (SCD) experience a disproportionately high use of health care resources. Several studies have examined depression and other negative mood states as risk factors for increased health care utilization; however, there have been no systematic reviews examining and summarizing this evidence in SCD. The aim of this systematic review, therefore, was to determine whether depression or depressive symptoms are associated with health care utilization among children and adults with SCD. We followed a quantitative systematic review protocol based on the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines and performed a literature search of records from January 1980 to April 2014 using six databases. Empirical studies were eligible if the sample was primarily composed of patients with SCD and included data on depression, mood disorder diagnosis or depressive symptoms and health care utilization. We included 12 studies involving 54 036 unique participants. The prevalence estimates for depression ranged from 2-57%. Seven studies found a significant, or marginally significant, association between depression and utilization while five did not. Patients reporting depression had an estimated 2.8 times greater relative risk of being a high utilizer, and 2.9 versus 1.8 hospitalizations per year on average compared to patients without depression. Overall, depressive symptoms are common in SCD and may increase risk for poor outcomes including health care utilization. The available studies on depression in SCD, however, are limited by small sample sizes, retrospective designs or short follow-up. This systematic review found a modest association between depression and health care utilization in SCD. PMID- 26991315 TI - In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper. AB - Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well characterized patients with DHR and to develop new tests for diagnosis. PMID- 26991318 TI - Resurfaced cell-penetrating nanobodies: A potentially general scaffold for intracellularly targeted protein discovery. AB - By virtue of their size, functional group diversity, and complex structure, proteins can often recognize and modulate disease-relevant macromolecules that present a challenge to small-molecule reagents. Additionally, high-throughput screening and evolution-based methods often make the discovery of new protein binders simpler than the analogous small-molecule discovery process. However, most proteins do not cross the lipid bilayer membrane of mammalian cells. This largely limits the scope of protein therapeutics and basic research tools to those targeting disease-relevant receptors on the cell surface or extracellular matrix. Previously, researchers have shown that cationic resurfacing of proteins can endow cell penetration. However, in our experience, many proteins are not amenable to such extensive mutagenesis. Here, we report that nanobodies-a small and stable protein that can be evolved to recognize virtually any disease relevant receptor-are amenable to cationic resurfacing, which results in cell internalization. Once internalized, these nanobodies access the cytosol. Polycationic resurfacing does not appreciably alter the structure, expression, and function (target recognition) of a previously reported GFP-binding nanobody, and multiple nanobody scaffolds are amenable to polycationic resurfacing. Given this, we propose that polycationic resurfaced cell-penetrating nanobodies might represent a general scaffold for intracellularly targeted protein drug discovery. PMID- 26991319 TI - Anti-Inflammatory Effects of Acupuncture Stimulation via the Vagus Nerve. AB - Although acupuncture therapy is widely used in traditional Asian medicine for the treatment of diverse internal organ disorders, its underlying biological mechanisms are largely unknown. Here, we investigated the functional involvement of acupuncture stimulation (AS) in the regulation of inflammatory responses. TNF alpha production in mouse serum, which was induced by lipopolysaccharide (LPS) administration, was decreased by manual acupuncture (MAC) at the zusanli acupoint (stomach36, ST36). In the spleen, TNF-alpha mRNA and protein levels were also downregulated by MAC and were recovered by using a splenic neurectomy and a vagotomy. c-Fos, which was induced in the nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve (DMV) by LPS and electroacupuncture (EAC), was further increased by focal administration of the AMPA receptor blocker CNQX and the purinergic receptor antagonist PPADS. TNF-alpha levels in the spleen were decreased by CNQX and PPADS treatments, implying the involvement of inhibitory neuronal activity in the DVC. In unanesthetized animals, both MAC and EAC generated c-Fos induction in the DVC neurons. However, MAC, but not EAC, was effective in decreasing splenic TNF-alpha production. These results suggest that the therapeutic effects of acupuncture may be mediated through vagal modulation of inflammatory responses in internal organs. PMID- 26991320 TI - Synthesis of (3) H, (2) H4 and (14) C-SCH 417690 (Vicriviroc). AB - Vicriviroc or SCH 417690 is a potent and selective antagonist of the CCR5 receptor. CCR5 receptor antagonists have the potential for the treatment of HIV infections. Four distinct isotopically labelled forms of SCH 417690 were synthesized. Low specific activity [(3) H]SCH 417690 was prepared for a preliminary absorption, distribution, metabolism and excretion evaluation of the compound and [(14) C]SCH 417690 for more definitive absorption, distribution, metabolism and excretion work, including an absorption, metabolism and excretion study in man. In addition, high specific activity [(3) H]SCH 417690 was prepared for CCR5 receptor binding work and [(2) H4 ]SCH 417690 was prepared as an internal standard for a liquid chromatography-mass spectrometry bioanalytical method. The paper discusses the synthesis of four isotopically labelled forms of SCH 417690. PMID- 26991321 TI - Availability of the lateral calcaneal region as a donor site of free flaps. AB - INTRODUCTION: Various methods have been used for the coverage of soft-tissue defects, such as local and free flaps, as well as perforator flaps performed using even supermicrosurgery. However, the techniques have some limitations regarding flap size and location when used to reconstruct small defects. We introduced the lateral calcaneal region as a donor site for free flaps in order to overcome these disadvantages and presented the results from a series of cases. PATIENTS AND METHODS: A retrospective chart review was performed on 10 patients with small soft-tissue defects who underwent reconstruction with a lateral calcaneal free flap between January 2011 and May 2014. The reconstruction was performed on the defects at medial and lateral plantar area, dorsum of the foot, great toes and preauricular area. RESULTS: The size of the flaps ranged from 2.5 * 2.5 cm to 4.5 * 4.5 cm. The flaps exhibited complete survival in five cases. Partial necrosis occurred in three cases, two cases healed with secondary intention, and one case required a skin graft. The donor sites were treated with skin grafts and healed completely, with no complications. CONCLUSION: Lateral calcaneal free flaps have several advantages, such as anatomically constant pedicles, a pliable and thin texture, and the ability to be used as sensory flaps. They therefore represent an alternative option when conventional local or free flaps are not suitable, especially in cases of small defects. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:494-501, 2017. PMID- 26991322 TI - The endophytic symbiont Epichloe festucae establishes an epiphyllous net on the surface of Lolium perenne leaves by development of an expressorium, an appressorium-like leaf exit structure. AB - Epichloe festucae forms a mutualistic symbiotic association with Lolium perenne. This biotrophic fungus systemically colonizes the intercellular spaces of aerial tissues to form an endophytic hyphal network. E. festucae also grows as an epiphyte, but the mechanism for leaf surface colonization is not known. Here we identify an appressorium-like structure, which we call an expressorium that allows endophytic hyphae to penetrate the cuticle from the inside of the leaf to establish an epiphytic hyphal net on the surface of the leaf. We used a combination of scanning electron, transmission electron and confocal laser scanning microscopy to characterize this novel fungal structure and determine the composition of the hyphal cell wall using aniline blue and wheat germ agglutinin labelled with Alexafluor-488. Expressoria differentiate immediately below the cuticle in the leaf blade and leaf sheath intercalary cell division zones where the hyphae grow by tip growth. Differentiation of this structure requires components of both the NoxA and NoxB NADPH oxidase complexes. Major remodelling of the hyphal cell wall occurs following exit from the leaf. These results establish that the symbiotic association of E. festucae with L. perenne involves an interconnected hyphal network of both endophytic and epiphytic hyphae. PMID- 26991323 TI - Transplantation tolerance: Coming of age. PMID- 26991324 TI - Feasibility Study of Transthoracic Echocardiography for Coronary Slow Flow Phenomenon Evaluation: Validation by Coronary Angiography. AB - OBJECTIVE: This study aimed to assess echocardiography parameters in CSFP evaluation. METHODS: This study enrolled 79 consecutive patients with CSFP validated by coronary angiography and control individuals with normal coronary flow. Coronary flow rates were determined by corrected CTFC. Clinical and coronary angiography data and coronary parameters assessed by echocardiography using the CFI were recorded. RESULTS: Baseline characteristics were similar between the two groups. Patients with CSFP were predominantly males, with higher BMI values, weights and triglyceride levels (p < 0.05), but lower platelet counts (p < 0.05). Conventional echocardiography parameters were similar in the two groups. However, echocardiographic measurements of the LAD, including PDV, MDV, PDP, MDP and VTI, in the CSFP group were lower compared with control values (p < 0.05). BMI was positively correlated with CSFP. LAD's CTFC showed strong inverse correlations with PDV, MDV, PDP, and MDP in CSFP groups. ROC curve analysis revealed that coronary artery flow-related parameters occupied more than half of the AUC. CONCLUSIONS: CSFP could be identified with the help of echocardiography. PMID- 26991325 TI - Serum Osteoprotegerin Levels Related With Cardiovascular Risk Factors in Chronic Kidney Disease. AB - BACKGROUND: To evaluate osteoprotegerin (OPG) levels in relation to cardiovascular (CV) risk factors in patients with chronic kidney disease (CKD) on different regimens of renal replacement therapy. METHODS: A total of 143 patients with CKD and 30 healthy controls were included in this study and divided into five categories, including predialysis patients with chronic renal failure (preD; n = 36), chronic peritoneal dialysis patients (PD; n = 36), hemodialysis patients (HD; n = 35), renal transplant patients (RT; n = 36), and controls (n = 30). Data on demographics, concomitant diseases and CV risk factors, serum OPG levels, and correlates of serum OPG levels were determined. RESULTS: Serum OPG (pmol/l) levels were significantly higher in HD (P <0.001 for each), PD (P <0.001 for each), and preD (P <0.01 vs. control, P <0.05 vs. RT) groups than RT and control groups. Diabetics than nondiabetics in HD (P = 0.008), PD (P = 0.024), and RT (P = 0.004) groups and males than females in PD group (P = 0.021) had higher OPG levels. Serum OPG levels were associated positively with age in HD (P <0.001), PD (P = 0.001), and in overall population (P <0.001). CONCLUSION: Our findings revealed increased serum levels of OPG in dialysis and preD patients compared to RT and controls. In the patient groups receiving two dialysis treatment, the levels were worse, indicating a more pronounced vascular injury. Age, C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), and cystatin C (CysC) in CKD patients, CRP and PTH in the control subjects, and age and BMI in the overall population were the significant correlates of serum OPG levels. PMID- 26991327 TI - A dramatic effect of oxygen on protection of human cells against gamma-radiation by lycopene. AB - Reducing radiation damage is important and dietary antioxidants that can protect cells from such damage are of value. Dietary lycopene, a carotenoid found in tomatoes, protects human lymphoid cell membranes from damage by gamma-radiation. We report that such protective effects are remarkably reduced as the oxygen concentration increases - near zero at 100% oxygen from fivefold protection at 20% oxygen and, dramatically, from 50-fold protection at 0% oxygen. Such huge differences imply that under higher oxygen concentrations lycopene could lead to improved cancer therapy using gamma-radiation. The cells are not efficiently protected from the superoxide radical by lycopene. Noncellular studies suggest molecular mechanisms for the oxygen effect. PMID- 26991326 TI - Community Rates of IgG4 Antibodies to Ascaris Haemoglobin Reflect Changes in Community Egg Loads Following Mass Drug Administration. AB - BACKGROUND: Conventional diagnostic methods for human ascariasis are based on the detection of Ascaris lumbricoides eggs in stool samples. However, studies of ascariasis in pigs have shown that the prevalence and the number of eggs detected in the stool do not correlate well with exposure of the herd to the parasite. On the other hand, an ELISA test measuring antibodies to Ascaris suum haemoglobin (AsHb) has been shown to be useful for estimating transmission intensity on pig farms. In this study, we further characterized the AsHb antigen and screened samples from a population-based study conducted in an area that is endemic for Ascaris lumbricoides in Indonesia to assess changes in AsHb antibody rates and levels in humans following mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS: We developed and evaluated an ELISA to detect human IgG4 antibodies to AsHb. We tested 1066 plasma samples collected at different times from 599 subjects who lived in a village in rural Indonesia that was highly endemic for ascariasis. The community received 6 rounds of MDA for lymphatic filariasis with albendazole plus diethylcarbamazine between 2002 and 2007. While the AsHb antibody assay was not sensitive for detecting all individuals with Ascaris eggs in their stools, the percentage of seropositive individuals decreased rapidly following MDA. Reductions in antibody rates reflected decreased mean egg output per person both at the community level and in different age groups. Two years after the last round of MDA the community egg output and antibody prevalence rate were reduced by 81.6% and 78.9% respectively compared to baseline levels. CONCLUSION/SIGNIFICANCE: IgG4 antibody levels to AsHb appear to reflect recent exposure to Ascaris. The antibody prevalence rate may be a useful indicator for Ascaris transmission intensity in communities that can be used to assess the impact of control measures on the force of transmission. PMID- 26991328 TI - Is there a Publication Bias in Behavioural Intranasal Oxytocin Research on Humans? Opening the File Drawer of One Laboratory. AB - The neurohormone oxytocin (OT) has been one the most studied peptides in behavioural sciences over the past two decades. Primarily known for its crucial role in labour and lactation, a rapidly growing literature suggests that intranasal OT (IN-OT) may also play a role in the emotional and social lives of humans. However, the lack of a convincing theoretical framework explaining the effects of IN-OT that would also allow the prediction of which moderators exert their effects and when has raised healthy skepticism regarding the robustness of human behavioural IN-OT research. Poor knowledge of the exact pharmacokinetic properties of OT, as well as crucial statistical and methodological issues and the absence of direct replication efforts, may have lead to a publication bias in the IN-OT literature, with many unpublished studies with null results remaining buried in laboratory drawers. Is there a file drawer problem in IN-OT research? If this is the case, it may also be true in our own laboratory. The present study aims to answer this question, document the extent of the problem and discuss its implications for OT research. For eight studies (including 13 dependent variables overall, as assessed through 25 different paradigms) performed in our laboratory between 2009 and 2014 on 453 subjects, the results obtained were too often not those that were expected. Only five publications emerged from our studies and only one of these reported a null finding. After realising that our publication portfolio has become less and less representative of our actual findings and because the nonpublication of our data might contribute to generating a publication bias in IN-OT research, we decided to retrieve these studies from our drawer and encourage other laboratories to do the same. PMID- 26991329 TI - Baseline level of 30-min plasma glucose is an independent predictor of incident diabetes among Asian Indians: analysis of two diabetes prevention programmes. AB - BACKGROUND: The objective was to study the ability of the 30-min plasma glucose (30-min PG) during an oral glucose tolerance test to predict the future risk of type 2 diabetes among Asian Indians with impaired glucose tolerance. METHODS: For the present analyses, we utilized data from 753 participants from two diabetes primary prevention studies, having complete data at the end of the study periods, including 236 from Indian Diabetes Prevention Programme-1 and 517 from the 2013 study. Baseline 30-min PG values were divided into tertiles: T1 < 9.1 mmol/L (<163.0 mg/dL); T2 9.2-10.4 mmol/L (164.0-187.0 mg/dL) and T3 >= 10.4 mmol/L (>=188 mg/dL). The predictive values of tertiles of 30-min PG for incident diabetes were assessed using Cox regression analyses RESULTS: At the end of the studies, 230 (30.5%) participants developed diabetes. Participants with higher levels of 30-min PG were more likely to have increased fasting, 2-h PG and HbA1c levels, increased prevalence of impaired fasting glucose and decreased beta cell function. The progression rate of diabetes increased with increasing tertiles of 30-min PG. Cox's regression analysis showed that 30-min PG was an independent predictor of incident diabetes after adjustment for an array of covariates [Hazard Ratio (HR):1.44 (1.01-2.06)] CONCLUSIONS: This prospective analysis demonstrates, for the first time, an independent association between an elevated 30-min PG level and incident diabetes among Asian Indians with impaired glucose tolerance. Predictive utility of glycemic thresholds at various time points other than the traditional fasting and 2-h PG values should therefore merit further consideration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991331 TI - Enzymatic characterisation of the immobilised Alcalase to hydrolyse egg white protein for potential allergenicity reduction. AB - BACKGROUND: This study examined technique characteristics of the immobilised Alcalase to hydrolyse egg white protein for potential allergenicity reduction. Alcalase was immobilised covalently on carboxyl-functionalised magnetic beads by carbodiimide activation. The technique characteristics of the immobilised Alcalase were investigated, followed by determining the degrees of hydrolysis (DH), immunoglobulin G (IgG) binding, and IgE binding of the digested egg white protein by immobilised Alcalase. RESULTS: Enzymatic activity, enzyme loading, and immobilisation yield of the prepared immobilised Alcalase were 20.55 U mg-1 , 925 mg g-1 , and 45%, respectively. Immobilised Alcalase showed maximum activity at pH 8.0 and 60 degrees C. Compared with free Alcalase, immobilised Alcalase exhibited better thermal and storage stability. Moreover, immobilised Alcalase can be reused 10 times and still maintained 55% of its initial activity. Partial hydrolysis of egg white protein by immobilised Alcalase can effectively reduce IgG and IgE binding of the hydrolysates. CONCLUSION: This study indicates that the immobilised Alcalase can be used to hydrolyse continuously egg white protein for potential allergenicity reduction. (c) 2016 Society of Chemical Industry. PMID- 26991332 TI - Development of a syn-Selective Mannich Reaction of Aldehydes with Propargylic Imines by Dual Catalysis: Asymmetric Synthesis of Functionalized Propargylic Amines. AB - Direct coupling of enolizable aldehydes with C-alkynyl imines is realized affording the corresponding propargylic Mannich adducts of syn configuration, thus complementing previous methods that gave access to the anti-isomers. The combination of proline and a urea Bronsted base cocatalyst is key for the reactions to proceed under very mild conditions (3-10 mol % catalyst loading, dichloromethane as solvent, -20 degrees C, 1.2 molar equivalents of aldehyde) and with virtually total stereocontrol (syn/anti ratio up to 99:1; ee up to 99 %). Some possibilities of further chemical elaboration of adducts are also briefly illustrated. PMID- 26991330 TI - Longitudinal Intergenerational Birth Cohort Designs: A Systematic Review of Australian and New Zealand Studies. AB - BACKGROUND: The longitudinal birth cohort design has yielded a substantial contribution to knowledge of child health and development. The last full review in New Zealand and Australia in 2004 identified 13 studies. Since then, birth cohort designs continue to be an important tool in understanding how intrauterine, infant and childhood development affect long-term health and well being. This updated review in a defined geographical area was conducted to better understand the factors associated with successful quality and productivity, and greater scientific and policy contribution and scope. METHODS: We adopted the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach, searching PubMed, Scopus, Cinahl, Medline, Science Direct and ProQuest between 1963 and 2013. Experts were consulted regarding further studies. Five inclusion criteria were used: (1) have longitudinally tracked a birth cohort, (2) have collected data on the child and at least one parent or caregiver (3) be based in Australia or New Zealand, (4) be empirical in design, and (5) have been published in English. RESULTS: 10665 records were initially retrieved from which 23 birth cohort studies met the selection criteria. Together these studies recruited 91,196 participants, with 38,600 mothers, 14,206 fathers and 38,390 live births. Seventeen studies were located in Australia and six in New Zealand. Research questions initially focused on the perinatal period, but as studies matured, longer-term effects and outcomes were examined. CONCLUSIONS: This review demonstrates the significant yield from this effort both in terms of scientific discovery and social policy impact. Further opportunities have been recognised with cross-study collaboration and pooling of data between established and newer studies and international studies to investigate global health determinants. PMID- 26991334 TI - Crohn's disease imaging in the emergency department. PMID- 26991333 TI - H2 -Fueled ATP Synthesis on an Electrode: Mimicking Cellular Respiration. AB - ATP, the molecule used by living organisms to supply energy to many different metabolic processes, is synthesized mostly by the ATPase synthase using a proton or sodium gradient generated across a lipid membrane. We present evidence that a modified electrode surface integrating a NiFeSe hydrogenase and a F1 F0 -ATPase in a lipid membrane can couple the electrochemical oxidation of H2 to the synthesis of ATP. This electrode-assisted conversion of H2 gas into ATP could serve to generate this biochemical fuel locally when required in biomedical devices or enzymatic synthesis of valuable products. PMID- 26991335 TI - Influences on independent nurse prescribers' antimicrobial prescribing behaviour: a systematic review. AB - AIMS AND OBJECTIVES: To present the findings of a systematic review which explored the influences on the antimicrobial prescribing behaviour of independent nurse prescribers. BACKGROUND: Antimicrobial resistance is an urgent public health concern and inappropriate antibiotic prescribing is linked to an increase in this resistance. With a growing number of nursing staff potentially prescribing. DESIGN: A systematic review. METHODS: A comprehensive search strategy was employed to identify appropriate research papers. Results were screened for relevance using eligibility criteria, and the assessment of the methodological quality of the papers was conducted using a critical appraisal tool. RESULTS: Seven studies were found which explored influences on nurse prescribers' antimicrobial prescribing behaviour. Three of these expected that an antimicrobial would be given and therefore influences discussed were on the choice of the antimicrobial given. Guidelines/protocols, safety, tolerability and efficacy of the antimicrobial itself, patient/parent pressure and training/experience were mentioned as influencing factors within the reported studies. The other four studies explored influences on whether to prescribe an antimicrobial or not and also found that guidelines/protocols were an influencing factor, however, the influence occurring most frequently was diagnostic uncertainty. CONCLUSIONS: The studies were limited by methodological issues and therefore further research is recommended to explore all influencing factors on prescriber behaviour. RELEVANCE TO CLINICAL PRACTICE: It has been recommended that interventions to change healthcare professionals' behaviour must be based on theory-based research. Future research should therefore focus on the use of sound theoretical frameworks in the planning of the studies if we are to be able to understand and, if required, change nurses' behaviours. PMID- 26991337 TI - Structure and outcomes of interdisciplinary rounds in hospitalized medicine patients: A systematic review and suggested taxonomy. AB - BACKGROUND: Interdisciplinary rounds (IDR) have been described to improve outcomes. However, there is limited understanding of optimal IDR design. PURPOSE: To systematically review published reports of IDR to catalog types of IDR and outcomes, and assess the influence of IDR design on outcomes. DATA SOURCES: Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Journals Ovid, Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), and PubMed from 1990 through December 2014, and hand searching of article bibliographies. STUDY SELECTION: Experimental, quasiexperimental, and observation studies in English-language literature where physicians rounded with another healthcare professional in inpatient medicine units. DATA EXTRACTION: Studies were abstracted for study setting and characteristics, and design and outcomes of IDR. DATA SYNTHESIS: Twenty-two studies were included in the qualitative analysis. Many were of low to medium quality with few high-quality studies. There is no clear definition of IDR in the literature. There was wide variation in IDR design and team composition across studies. We found three different models of IDR: pharmacist focused, bedside rounding, and interdisciplinary team rounding. There are reasonable data to support an association with length of stay and staff satisfaction but little data on patient safety or satisfaction. Positive outcomes may be related to particular components of IDR design, but the relationship between design and outcomes remains unclear. CONCLUSIONS: Future studies should be more deliberately designed and fully reported with careful attention to team composition and features of IDR and their impact on selected outcomes. We present a proposed IDR definition and taxonomy for future studies. Journal of Hospital Medicine 2016;11:513-523. (c) 2016 Society of Hospital Medicine. PMID- 26991338 TI - Using different growth references to measure thinness and overweight among Swedish primary school children showed considerable variations. AB - AIM: The study compared how four different growth references determined the prevalence of thinness and overweight, based on height and weight measurements from a nationally representative sample of Swedish children from seven to nine years of age. METHODS: The height and weight measurements of 4518 Swedish schoolchildren aged seven to nine years were carried out in 2008 using a standardised protocol. The prevalence of different degrees of thinness and overweight was calculated using international growth references from the World Health Organization, the International Obesity Task Force and two Swedish growth references from Werner and Karlberg. RESULTS: Depending on which growth reference we used, the prevalence of different degrees of thinness varied from 7.5% to 16.9% for the boys and 6.9% to 13.7% for the girls, while the prevalence of overweight, including obesity and severe obesity, varied from 16.5% to 25.7% for the boys and 18.2 to 25.2% for the girls. There were also significant gender differences depending on the growth reference we used. CONCLUSION: Using four different growth references, two international and two Swedish, produced wide variations in the prevalence of thinness and overweight, together with significant gender differences. In the absence of a global definition, we need both national and international growth references. PMID- 26991336 TI - The impact of genetic polymorphisms on the pharmacokinetics of efavirenz in African children. AB - AIMS: Using a model-based approach, the efavirenz steady-state pharmacokinetics in African children is characterized, quantifying demographic and genotypic effects on the drug's disposition. Simulations are also conducted allowing prediction of optimized doses of efavirenz in this population. METHODS: We modelled the steady-state population pharmacokinetics of efavirenz in Ugandan and Zambian children using nonlinear mixed-effects modelling. Individual mid-dose efavirenz concentrations were derived and simulations explored genotype-based dose optimization strategies. RESULTS: A two-compartment model with absorption through transit compartments well described 2086 concentration-time points in 169 children. The combined effect of single nucleotide polymorphisms (SNPs) 516G>T and 983T>C explained 44.5% and 14.7% of the variability in efavirenz clearance and bioavailability, respectively. The detected frequencies of composite CYP2B6 genotype were 0.33 for 516GG|983TT, 0.35 for 516GT|983TT, 0.06 for 516GG|983TC, 0.18 for 516TT|983TT, 0.07 516GT|983TC and 0.01 for 516GG|983CC. The corresponding estimated clearance rates were 6.94, 4.90, 3.93, 1.92, 1.36, and 0.74 l h(-1) for a 15.4 kg child and median (95% CI) observed mid-dose concentrations 1.55 (0.51-2.94), 2.20 (0.97-4.40), 2.03 (1.19-4.53), 7.55 (2.40 14.74), 7.79 (3.66-24.59) and 18.22 (11.84-22.76) mg l(-1) , respectively. Simulations showed that wild-type individuals had exposures at the bottom of therapeutic range, while slower metabolizers were overexposed. CONCLUSIONS: Dosage guidelines for African children should take into consideration the combined effect of SNPs CYP2B6 516G>T and 983T>C. PMID- 26991339 TI - N- and O-linked glycosylation site profiling of the human basic salivary proline rich protein 3M. AB - In the present study, we show that the heterogeneous mixture of glycoforms of the basic salivary proline-rich protein 3M, encoded by PRB3-M locus, is a major component of the acidic soluble fraction of human whole saliva in the first years of life. Reversed-phase high-performance liquid chromatography with high resolution electrospray ionization mass spectrometry analysis of the intact proteoforms before and after N-deglycosylation with Peptide-N-Glycosidase F and tandem mass spectrometry sequencing of peptides obtained after Endoproteinase GluC digestion allowed the structural characterization of the peptide backbone and identification of N- and O-glycosylation sites. The heterogeneous mixture of the proteoforms derives from the combination of 8 different neutral and sialylated glycans O-linked to Threonine 50, and 33 different glycans N-linked to Asparagine residues at positions 66, 87, 108, 129, 150, 171, 192, and 213. PMID- 26991340 TI - Chronic hepatitis B increases mortality and complexity among HIV-coinfected patients in South Africa: a cohort study. AB - OBJECTIVES: To assess the effect of chronic hepatitis B on survival and clinical complexity among people living with HIV following antiretroviral therapy (ART) initiation. METHODS: We evaluated mortality and single-drug substitutions up to 3 years from ART initiation (median follow-up 2.75 years; interquartile range 2-3 years) among patients with and without chronic hepatitis B (CHB) enrolled in a workplace HIV care programme in South Africa. RESULTS: Mortality was increased for CHB patients with hepatitis B virus (HBV) DNA levels > 10 000 copies/mL (adjusted hazard ratio 3.1; 95% confidence interval 1.2-8.0) compared with non CHB patients. We did not observe a similar difference between non-CHB patients and those with CHB and HBV DNA < 10 000 copies/mL (adjusted hazard ratio 0.70; 95% confidence interval 0.2-2.3). Single-drug substitutions occurred more frequently among coinfected patients regardless of HBV DNA level. CONCLUSIONS: Our findings suggest that CHB may increase mortality and complicate ART management. PMID- 26991341 TI - Regulating the osteogenic function of rhBMP 2 by different titanium surface properties. AB - Bone morphogenetic protein 2 (BMP-2) is important for regulating the osteogenic differentiation of mesenchymal stem cells and the response of bone tissue. It adsorbs on the surface of biomedical implants immediately and plays a role of mediator between the materials surfaces and the host cells. Studies usually connect the material surface properties and the new bone formation directly. However, interaction between the adsorbed BMP-2 on the implant surface and the cells in the tissue is the key to explaining the osteogenic properties of the material. So, in this article, we investigated the conformational and functional changes induced by the surface modified titanium metals. We found that the alpha helix and beta-sheet structure of rhBMP-2 can be well maintained on the anodic oxidation treated titanium surface. The osteogenic function of rhBMP-2 can sustain for a relatively long time even though there is less amount adhere to the surface compared with that on the acid alkali treated titanium. Surface properties, especially the morphology enable a larger amount of rhBMP-2 to adsorb to the surface of the acid alkali treated titanium, but the conformation of the protein is severely influenced. The percentage of alpha-helix structure is also significantly decreased so that the efficacy of rhBMP-2 is only maintained in the early time. This study indicated that different surface modification of the surface could regulate the structure of rhBMP-2 and then further influence its osteogenic function. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1882-1893, 2016. PMID- 26991342 TI - Emergence of Lumpy Skin Disease in Greece, 2015. AB - Lumpy skin disease was first reported in the EU, Greece, in August 2015. Until the end of December 2015, six regional units have been affected in northern Greece and the island of Limnos. This article presents the epidemiological situation, the diagnosis, the control measures including emergency vaccination and the preliminary conclusions from the experience gained. PMID- 26991343 TI - A preliminary microarray assay of the miRNA expression signatures in buccal mucosa of oral submucous fibrosis patients. AB - OBJECTIVES: The objectives of this study are threefold: First is to perform a preliminary microarray analysis of miRNA expression profile to filter out differentially expressed miRNA in oral submucous fibrosis, second is to perform a bioinformatics analysis to identify miRNA-specific predicted genes, and third to retrieve those miRNAs from literature and account for the findings of our investigations. METHODS: Buccal mucosa samples from three clinically evident OSF patients and three normal volunteers were collected. Agilent Human miRNA microarray experiments were carried out to analyze the miRNA expression profile in both OSF and normal tissues. To identify molecular pathways potentially altered by expression of miRNAs, DAVID software was used. This application performs an enrichment analysis of multiple miRNA target genes comparing each set of miRNA targets to known KEGG pathway. RESULTS: A total of 11 unique miRNAs were differentially expressed. The overexpressed miRNAs were hsa-miR-455-3p, hsa-miR 455-5p, and hsa-miR-623, and underexpressed miRNAs were hsa-miR-1290, hsa-miR 3180-3p, hsa-miR-4792, hsa-miR-509-3-5p, hsa-miR-5189, hsa-miR-610, hsa-miR-760, and hsa-miR-921. Six miRNAs namely miR-455, miR-760, miR-623, miR-610 and miR-509 3-5p were selected. CONCLUSION: This study shows that miRNA chip can be used for high-throughput screening of miRNA. Target prediction and annotation of the miRNAs demonstrated that the binding, metabolic process, molecular, and cellular process are the most common functions of the predicted targets of these newly identified miRNAs. PMID- 26991346 TI - Strong sexual selection in males against a mutation load that reduces offspring production in seed beetles. AB - Theory predicts that sexual reproduction can increase population viability relative to asexual reproduction by allowing sexual selection in males to remove deleterious mutations from the population without large demographic costs. This requires that selection acts more strongly in males than females and that mutations affecting male reproductive success have pleiotropic effects on population productivity, but empirical support for these assumptions is mixed. We used the seed beetle Callosobruchus maculatus to implement a three-generation breeding design where we induced mutations via ionizing radiation (IR) in the F0 generation and measured mutational effects (relative to nonirradiated controls) on an estimate of population productivity in the F1 and effects on sex-specific competitive lifetime reproductive success (LRS) in the F2 . Regardless of whether mutations were induced via F0 males or females, they had strong negative effects on male LRS, but a nonsignificant influence on female LRS, suggesting that selection is more efficient in removing deleterious alleles in males. Moreover, mutations had seemingly shared effects on population productivity and competitive LRS in both sexes. Thus, our results lend support to the hypothesis that strong sexual selection on males can act to remove the mutation load on population viability, thereby offering a benefit to sexual reproduction. PMID- 26991347 TI - Study of Interlaminar Lumbar Epidural Steroid Injections Suffers From Flawed Methodology and Invalid Conclusions. PMID- 26991345 TI - Staff perspectives of relationships in aged care: A qualitative approach. AB - AIM: To explore aged care staff perceptions and experience of their relationships with co-workers, older people and families via pragmatic exploratory interviews. METHODS: Thirty-nine direct care staff from seven residential age care facilities and 12 community organisations were interviewed. RESULTS: Staff felt that their capacity to develop therapeutic relationships with older people and families was impeded by care tasks and concerns regarding professional boundaries. Positive relationships between staff-family and staff-staff are hindered by staff perceptions of undue care demands, high family expectations, and staff-staff conflict within a hierarchical context and between work shifts. CONCLUSION: A relationship-centred approach to care as well as staff training and education should be encouraged to assist the development of therapeutic relationships and the management of professional boundaries. PMID- 26991344 TI - Impact of KRAS, BRAF, PIK3CA, TP53 status and intraindividual mutation heterogeneity on outcome after liver resection for colorectal cancer metastases. AB - We determined prognostic impact of KRAS, BRAF, PIK3CA and TP53 mutation status and mutation heterogeneity among 164 colorectal cancer (CRC) patients undergoing liver resections for metastatic disease. Mutation status was determined by Sanger sequencing of a total of 422 metastatic deposits. In univariate analysis, KRAS (33.5%), BRAF (6.1%) and PIK3CA (13.4%) mutations each predicted reduced median time to relapse (TTR) (7 vs. 22, 3 vs. 16 and 4 vs. 17 months; p < 0.001, 0.002 and 0.023, respectively). KRAS and BRAF mutations also predicted a reduced median disease-specific survival (DSS) (29 vs. 51 and 16 vs. 49 months; p <0.001 and 0.008, respectively). No effect of TP53 (60.4%) mutation status was observed. Postoperative, but not preoperative chemotherapy improved both TTR and DSS (p < 0.001 for both) with no interaction with gene mutation status. Among 94 patients harboring two or more metastatic deposits, 13 revealed mutation heterogeneity across metastatic deposits for at least one gene. Mutation heterogeneity predicted reduced median DSS compared to homogeneous mutations (18 vs. 37 months; p = 0.011 for all genes; 16 vs. 26 months; p < 0.001 analyzing BRAF or KRAS mutations separately). In multivariate analyses, KRAS or BRAF mutations consistently predicted poor TRR and DSS. Mutation heterogeneity robustly predicted DSS but not TTR, while postoperative chemotherapy improved both TTR and DSS. Our findings indicate that BRAF and KRAS mutations as well as mutation heterogeneity predict poor outcome in CRC patients subsequent to liver resections and might help guide treatment decisions. PMID- 26991348 TI - Validity of Certified Registered Nurse Anesthetist Complication Rates When Performing Fluoroscopic Guided Interlaminar Lumbar Epidural Steroid Injections. PMID- 26991349 TI - Blood Glucose Control in Noncritically Ill Patients Is Associated With a Decreased Length of Stay, Readmission Rate, and Hospital Mortality. AB - PURPOSE: Multiple studies have shown that hyperglycemia correlates with mortality and morbidity in critically ill patients. This has not been demonstrated in noncritically hospitalized patients. The primary objective of this study was to determine whether glycemic control shortens the length of stay (LOS). Secondary objectives included assessing readmissions, in-hospital mortality, and rates of hypoglycemia. METHODS: A retrospective review of hospitalized patients admitted between 2008 and 2012 with fingerstick blood sugar (FSBS) was performed. Patients were divided into two groups: "controlled" FSBS (>=80% of FSBS were <180 mg/dL) and "uncontrolled" FSBS (<80% of FSBS were <180 mg/dL). The average LOS (ALOS) in days, in-hospital mortality, readmission rates, and rates of hypoglycemia was compared. RESULTS: A total of 32,851 patient records were reviewed. ALOS for patients with controlled and uncontrolled FSBS was 5.86 and 6.17 days, respectively (p < .0001). Readmission within 30 days and hospital mortality were significantly lower in patients with controlled FSBS (p = .0000, .00001), whereas rates of hypoglycemia were significantly higher in the uncontrolled group (p = .00000). CONCLUSIONS: Glycemic control was associated with decreased LOS, hospital mortality, and 30-day readmission rate in noncritically ill patients regardless of the presence or absence of diabetes. PMID- 26991350 TI - Improving Operating Room Efficiency: First Case On-Time Start Project. AB - BACKGROUND: Operating rooms (ORs) are costly to run, and multiple factors influence efficiency. The first case on-time start (FCOS) of an OR is viewed as a harbinger of efficiency for the daily schedule. Across 26 ORs of a large, academic medical center, only 49% of cases started on time in October 2011. METHODS: The Perioperative Services Department engaged an interdisciplinary Operating Room Committee to apply Six Sigma tools to this problem. The steps of this project included (1) problem mapping, (2) process improvements to preoperative readiness, (3) informatics support improvements, and (4) continuous measurement and feedback. RESULTS: By June 2013, there was a peak of 92% first case on-time starts across service lines, decreasing to 78% through 2014, still significantly above the preintervention level of 49% (p = .000). Delay minutes also significantly decreased through the study period (p = .000). Across 2013, the most common delay owners were the patient, the surgeon, the facility, and the anesthesia department. CONCLUSIONS: Continuous and sustained improvement of first case on-time starts is attributed to tracking the FCOS metric, establishing embedded process improvement resources and creating transparency of data. This article highlights success factors and barriers to program success and sustainability. PMID- 26991351 TI - Circular piecewise regression with applications to cell-cycle data. AB - Applications of circular regression models appear in many different fields such as evolutionary psychology, motor behavior, biology, and, in particular, in the analysis of gene expressions in oscillatory systems. Specifically, for the gene expression problem, a researcher may be interested in modeling the relationship among the phases of cell-cycle genes in two species with differing periods. This challenging problem reduces to the problem of constructing a piecewise circular regression model and, with this objective in mind, we propose a flexible circular regression model which allows different parameter values depending on sectors along the circle. We give a detailed interpretation of the parameters in the model and provide maximum likelihood estimators. We also provide a model selection procedure based on the concept of generalized degrees of freedom. The model is then applied to the analysis of two different cell-cycle data sets and through these examples we highlight the power of our new methodology. PMID- 26991352 TI - Moving away from symptoms-based heart failure treatment: misperceptions and real risks for patients with heart failure. PMID- 26991353 TI - Oral healthcare providers' viewpoints in crucial role of education in oral self care behaviour. PMID- 26991354 TI - Appropriate baseline laboratory testing following ACEI or ARB initiation by Medicare FFS beneficiaries. AB - BACKGROUND: Laboratory testing to identify contraindications and adverse drug reactions is important for safety of patients initiating angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Rates and predictors of appropriate testing among Medicare fee-for-service beneficiaries are unknown. PURPOSE: The study's purpose was to examine baseline laboratory testing rates, identify predictors of suboptimal testing, and assess the prevalence of abnormal creatinine and potassium among beneficiaries initiating ACE inhibitors or ARBs. DESIGN AND SUBJECTS: Retrospective cohort of 101 376 fee for-service beneficiaries from 10 eastern US states in 1 July to 30 November 2011. MAIN MEASURES: Appropriate monitoring for serum creatinine or serum potassium was defined as evidence of an outpatient claim within 180 days before or 14 days after the index prescription fill date. KEY RESULTS: Thirty-eight percent of beneficiaries were men, 78% were White race, 26% had prevalent heart failure, and 89% had prevalent hypertension. Rates of appropriate baseline laboratory testing were 82.7% for potassium, 83.2% for creatinine, and 82.6% for both potassium and creatinine 180 days prior to initiation. In logistic regression, men (odds ratio [OR] = 1.15, 95% confidence interval [CI]: 1.11, 1.19), African-Americans (OR = 1.26, 95%CI: 1.20, 1.32), and beneficiaries with Alzheimer's disease and related disorders (OR = 1.22, 95%CI: 1.15, 1.28) or stroke (OR = 1.34, 95%CI: 1.26, 1.43) were more likely to experience suboptimal testing. At baseline, hyperkalemia was relatively uncommon (5.8%), and elevated creatinine values were rare (1.4%). CONCLUSIONS: Appropriate monitoring could be improved for African-American beneficiaries and beneficiaries with a history of stroke or Alzheimer's disease and related disorders initiating ACE inhibitors or ARBs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991355 TI - Genetic abnormalities associated with acute lymphoblastic leukemia. AB - Acute lymphoblastic leukemia (ALL) occurs with high frequency in childhood and is associated with high mortality in adults. Recent technical advances in next generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to ALL pathogenesis. Based on these genetic abnormalities, ALL is now being reclassified into newly identified subtypes. Philadelphia chromosome-like B-lineage ALL is one of the new high-risk subtypes characterized by genetic alterations that activate various signaling pathways, including those involving cytokine receptors, tyrosine kinases, and epigenetic modifiers. Philadelphia chromosome-like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses. Whole-genome sequencing studies of ALL patients and ethnically matched controls also identified inherited genetic variations in lymphoid neoplasm-related genes, which are likely to increase ALL susceptibility. These findings are directly relevant to clinical hematology, and further studies on this aspect could contribute to accurate diagnosis, effective monitoring of residual disease, and patient-oriented therapies. PMID- 26991356 TI - The Anticancer Activity of Organotelluranes: Potential Role in Integrin Inactivation. AB - Organic Te(IV) compounds (organotelluranes) differing in their labile ligands exhibited anti-integrin activities in vitro and anti-metastatic properties in vivo. They underwent ligand substitution with l-cysteine, as a thiol model compound. Unlike inorganic Te(IV) compounds, the organotelluranes did not form a stable complex with cysteine, but rather immediately oxidized it. The organotelluranes inhibited integrin functions, such as adhesion, migration, and metalloproteinase secretion mediation in B16F10 murine melanoma cells. In comparison, a reduced derivative with no labile ligand inhibited adhesion of B16F10 cells to a significantly lower extent, thus pointing to the importance of the labile ligands of the Te(IV) atom. One of the organotelluranes inhibited circulating cancer cells in vivo, possibly by integrin inhibition. Our results extend the current knowledge on the reactivity and mechanism of organotelluranes with different labile ligands and highlight their clinical potential. PMID- 26991357 TI - Should the non-operative management of appendicitis be the new standard of care? AB - Appendicitis is one of the most commonly encountered emergency presentations to the general surgical services. The operative management of this condition is associated with significant financial costs and represents a significant workload on the emergency surgical services. Negative appendicectomy rates remain high (20 25%) despite advancements in laboratory testing and imaging techniques. Recent data from randomized controlled trials suggests that non-operative management in patients presenting with uncomplicated or non-perforated acute appendicitis is a viable alternative, with only 23% of patients requiring an appendicectomy at 1 year and an overall reduction in complications. In view of this, the traditional teaching of mandatory appendicectomy for all patients with acute appendicitis should be challenged. This article briefly reviews the evidence that supports the use of diagnostic tests to reduce the negative appendicectomy rate and examines the potential selection criteria for non-operative management. The data raises the questions: can a 20-25% negative appendicectomy rate be defended as best practice and can the traditional dogma of early appendicectomy to prevent perforation be supported? PMID- 26991359 TI - Functional Reconstitution of a Pyruvate Dehydrogenase in the Cytosol of Saccharomyces cerevisiae through Lipoylation Machinery Engineering. AB - Acetyl-CoA is a key precursor for the biosynthesis of a wide range of fuels, chemicals, and value-added compounds, whose biosynthesis in Saccharomyces cerevisiae involves acetyl-CoA synthetase (ACS) and is energy intensive. Previous studies have demonstrated that functional expression of a pyruvate dehydrogenase (PDH) could fully replace the endogenous ACS-dependent pathway for cytosolic acetyl-CoA biosynthesis in an ATP-independent manner. However, the requirement for lipoic acid (LA) supplementation hinders its wide industrial applications. In the present study, we focus on the engineering of a de novo synthetic lipoylation machinery for reconstitution of a functional PDH in the cytosol of yeast. First, a LA auxotrophic yeast strain was constructed through the expression of the Escherichia coli PDH structural genes and a lipoate-protein ligase gene in an ACS deficient (acs1Delta acs2Delta) strain, based on which an in vivo acetyl-CoA reporter was developed for following studies. Then the de novo lipoylation pathway was reconstituted in the cytosol of yeast by coexpressing the yeast mitochondrial lipoylation machinery genes and the E. coli type II fatty acid synthase (FAS) genes. Alternatively, an unnatural de novo synthetic lipoylation pathway was constructed by combining the reversed beta-oxidation pathway with an acyl-ACP synthetase gene. To the best of our knowledge, reconstitution of natural and unnatural de novo synthetic lipoylation pathways for functional expression of a PDH in the cytosol of yeast has never been reported. Our study has laid a solid foundation for the construction and further optimization of acetyl-CoA overproducing yeast strains. PMID- 26991358 TI - Aging modulates the oscillatory dynamics underlying successful working memory encoding and maintenance. AB - Working memory is central to the execution of many daily functions and is typically divided into three phases: encoding, maintenance, and retrieval. While working memory performance has been repeatedly shown to decline with age, less is known regarding the underlying neural processes. We examined age-related differences in the neural dynamics that serve working memory by recording high density magnetoencephalography (MEG) in younger and older adults while they performed a modified, high-load Sternberg working memory task with letters as stimuli. MEG data were evaluated in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. A hierarchical regression was performed to investigate whether age moderated the relationship between oscillatory activity and accuracy on the working memory task. Our results indicated that the spatiotemporal dynamics of oscillatory activity in language related areas of the left fronto-temporal cortices were similar across groups. Age-related differences emerged during early encoding in the right-hemispheric homologue of Wernicke's area. Slightly later, group differences emerged in the homologue of Broca's area and these persisted throughout memory maintenance. Additionally, occipital alpha activity during maintenance was stronger, occurred earlier, and involved more cortical tissue in older adults. Finally, age significantly moderated the relationship between accuracy and neural activity in the prefrontal cortices. In younger adults, as prefrontal activity decreased, accuracy tended to increase. Our results are consistent with predictions of the compensation-related utilization of neural circuits hypothesis (CRUNCH). Such differences in the oscillatory dynamics could reflect compensatory mechanisms, which would aid working memory performance in older age. Hum Brain Mapp 37:2348 2361, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991360 TI - High-Throughput Screening of Na(V)1.7 Modulators Using a Giga-Seal Automated Patch Clamp Instrument. AB - Voltage-gated sodium (Na(V)) channels have an essential role in the initiation and propagation of action potentials in excitable cells, such as neurons. Of these channels, Na(V)1.7 has been indicated as a key channel for pain sensation. While extensive efforts have gone into discovering novel Na(V)1.7 modulating compounds for the treatment of pain, none has reached the market yet. In the last two years, new compound screening technologies have been introduced, which may speed up the discovery of such compounds. The Sophion Qube((r)) is a next generation 384-well giga-seal automated patch clamp (APC) screening instrument, capable of testing thousands of compounds per day. By combining high-throughput screening and follow-up compound testing on the same APC platform, it should be possible to accelerate the hit-to-lead stage of ion channel drug discovery and help identify the most interesting compounds faster. Following a period of instrument beta-testing, a Na(V)1.7 high-throughput screen was run with two Pfizer plate-based compound subsets. In total, data were generated for 158,000 compounds at a median success rate of 83%, which can be considered high in APC screening. In parallel, IC50 assay validation and protocol optimization was completed with a set of reference compounds to understand how the IC50 potencies generated on the Qube correlate with data generated on the more established Sophion QPatch((r)) APC platform. In summary, the results presented here demonstrate that the Qube provides a comparable but much faster approach to study Na(V)1.7 in a robust and reliable APC assay for compound screening. PMID- 26991362 TI - Pharmacological Modulation of GluK1 and GluK2 by NETO1, NETO2, and PSD95. AB - The association between the kainate receptors (KARs) GluK1 and GluK2 and the modifying proteins neuropilin- and tolloid-like 1 (NETO1), neuropilin- and tolloid-like 2 (NETO2), and postsynaptic density protein 95 (PSD95) is likely to produce distinct GluK1 and GluK2 pharmacology in postsynaptic neurons. However, little is known about their corresponding modulatory effects on GluK1 and GluK2 activity in high-throughput assays for cell-based drug discovery. Using heterologous cells that potentially mimic the response in native cells in a fluorescence imaging plate reader (FLIPR) assay, we have investigated assays that incorporate (1) coexpression of GluK1 or GluK2 with their modulatory proteins (NETO1, NETO2, PSD95) and/or (2) enablement of assays with physiological concentration of native GluK1 and GluK2 agonist (glutamate) in the absence of an artificial potentiator (e.g., concanavalin A [Con A]). We found that in the absence of Con A, both NETO1 and NETO2 accessory proteins are able to potentiate kainate- and glutamate-evoked GluK1-mediated Ca(2+) influx. We also noted the striking ability of PSD95 to enhance glutamate-stimulated potentiation effects of NETO2 on GluK1 without the need for Con A and with a robust signal that could be utilized for high-throughput FLIPR assays. These experiments demonstrate the utility of heterologous cells coexpressing PSD95/NETO2 with GluK1 or GluK2 in native cell-mimicking heterologous cell systems for high-throughput assays and represent new avenues into the discovery of KAR modulating therapies. PMID- 26991361 TI - Characterization of Endogenous Sodium Channels in the ND7-23 Neuroblastoma Cell Line: Implications for Use as a Heterologous Ion Channel Expression System Suitable for Automated Patch Clamp Screening. AB - The rodent neuroblastoma cell line, ND7-23, is used to express voltage-dependent sodium (Nav) and other neuronal ion channels resistant to heterologous expression in Chinese hamster ovary (CHO) or human embryonic kidney (HEK) cells. Their advantage is that they provide endogenous factors and signaling pathways to promote ion channel peptide folding, expression, and function at the cell surface and are also amenable to automated patch clamping. However, ND7-23 cells exhibit endogenous tetrodotoxin (TTX)-sensitive Nav currents, and molecular profiling has revealed the presence of Nav1.2, Nav1.3, Nav1.6, and Nav1.7 transcripts, but no study has determined which subtypes contribute to functional channels at the cell surface. We profiled the repertoire of functional Nav channels endogenously expressed in ND7-23 cells using the QPatch automated patch clamp platform and selective toxins and small molecules. The potency and subtype selectivity of the ligands (Icagen compound 68 from patent US-20060025415-A1-20060202, 4,9 anhydro TTX, and Protoxin-II) were established in human Nav1.3, Nav1.6, and Nav1.7 channel cell lines before application of selective concentrations to ND7-23 cells. Our data confirm previous studies that >97% of macroscopic Nav current in ND7-23 cells is carried by TTX-sensitive channels (300 nM TTX) and that Nav1.7 is the predominant channel contributing to this response (65% of peak inward current), followed by Nav1.6 (~20%) and negligible Nav1.3 currents (~2%). In addition, our data are the first to assess the Nav1.6 potency (50% inhibitory concentration [IC50] of 33 nM) and selectivity (50-fold over Nav1.7) of 4,9 anhydro TTX in human Nav channels expressed in mammalian cells, confirming previous studies of rodent Nav channels expressed in oocytes and HEK cells. PMID- 26991363 TI - Catch and Patch: A Pipette-Based Approach for Automating Patch Clamp That Enables Cell Selection and Fast Compound Application. AB - Manual patch clamp, the gold standard of electrophysiology, represents a powerful and versatile toolbox to stimulate, modulate, and record ion channel activity from membrane fragments and whole cells. The electrophysiological readout can be combined with fluorescent or optogenetic methods and allows for ultrafast solution exchanges using specialized microfluidic tools. A hallmark of manual patch clamp is the intentional selection of individual cells for recording, often an essential prerequisite to generate meaningful data. So far, available automation solutions rely on random cell usage in the closed environment of a chip and thus sacrifice much of this versatility by design. To parallelize and automate the traditional patch clamp technique while perpetuating the full versatility of the method, we developed an approach to automation, which is based on active cell handling and targeted electrode placement rather than on random processes. This is achieved through an automated pipette positioning system, which guides the tips of recording pipettes with micrometer precision to a microfluidic cell handling device. Using a patch pipette array mounted on a conventional micromanipulator, our automated patch clamp process mimics the original manual patch clamp as closely as possible, yet achieving a configuration where recordings are obtained from many patch electrodes in parallel. In addition, our implementation is extensible by design to allow the easy integration of specialized equipment such as ultrafast compound application tools. The resulting system offers fully automated patch clamp on purposely selected cells and combines high-quality gigaseal recordings with solution switching in the millisecond timescale. PMID- 26991364 TI - Electrocatalytic Hydrogen Production by a Nickel(II) Complex with a Phosphinopyridyl Ligand. AB - A novel nickel(II) complex [Ni(L)2 Cl]Cl with a bidentate phosphinopyridyl ligand 6-((diphenylphosphino)methyl)pyridin-2-amine (L) was synthesized as a metal complex catalyst for hydrogen production from protons. The ligand can stabilize a low Ni oxidation state and has an amine base as a proton transfer site. The X-ray structure analysis revealed a distorted square-pyramidal Ni(II) complex with two bidentate L ligands in a trans arrangement in the equatorial plane and a chloride anion at the apex. Electrochemical measurements with the Ni(II) complex in MeCN indicate a higher rate of hydrogen production under weak acid conditions using acetic acid as the proton source. The catalytic current increases with the stepwise addition of protons, and the turnover frequency is 8400 s(-1) in 0.1 m [NBu4 ][ClO4 ]/MeCN in the presence of acetic acid (290 equiv) at an overpotential of circa 590 mV. PMID- 26991365 TI - Predicting treatment outcome in psychological treatment services by identifying latent profiles of patients. AB - BACKGROUND: The outcomes of psychological therapies for anxiety and depression vary across individuals and symptom domains. Being able to predict treatment response from readily available patient data at presentation has potentially important benefits in aiding decisions about the most suitable interventions for a patient. This paper presents a method of identifying subgroups of patients using latent profile analysis, and comparing response to psychological treatments between these profiles. METHODS: All outpatients taken into treatment at two psychological treatment services in London, UK and who provided basic demographic information and standardized symptom measures were included in the analysis (n=16636). RESULTS: Latent Profile Analysis was performed on intake data to identify statistically different groups of patients, which were then examined in longitudinal analyses to determine their capacity to predict treatment outcomes. Comparison between profiles showed considerable variation in recovery (74-15%), deterioration rates (5-20%), and levels of attrition (17-40%). Further variation in outcomes was found within the profiles when different intensities of psychological intervention were delivered. LIMITATIONS: Latent profiles were identified using data from two services, so generalisability to other services should be considered. Routinely collected patient data was included, additional patient information may further enhance utility of the profiles. CONCLUSIONS: These results suggest that intake data can be used to reliably classify patients into profiles that are predictive of outcome to different intensities of psychological treatment in routine care. Algorithms based on these kinds of data could be used to optimize decision-making and aid the appropriate matching of patients to treatment. PMID- 26991366 TI - Decreased functional connectivity in the language regions in bipolar patients during depressive episodes but not remission. AB - BACKGROUND: Retardation of thought is a crucial clinical feature in patients with bipolar depression, characterized by dysfunctional semantic processing and language communication. However, the underlying neuropathological mechanisms remain largely unknown. The objective of this study was to evaluate the disruption in resting-state functional connectivity in 90 different brain regions during the depressive episodes of bipolar disorder and during disease remission. METHODS: Applying the whole brain and language regions of interest methods to the resting-state functional magnetic resonance imaging data, we explored the discrepancies in 90 brain regions' functional connectivity in 42 patients with bipolar disorder - 23 experiencing a depressive episode and 19 in remission - and 28 healthy controls matched for gender, age, and education. RESULTS: Bipolar depressive patients had significantly reduced connectivity strength in the language regions relative to healthy controls. Specifically, the affected regions included the left triangular part of the inferior frontal gyrus, left opercular part of the inferior frontal gyrus, left middle temporal gyrus, and left angular gyrus. However, no significant differences in these regions were observed between bipolar patients in remission and healthy controls. Furthermore, the decreased connectivity strength between the left middle temporal gyrus and right lingual gyrus showed significant positive correlation with the scores on the Hamilton Depression Rating Scale. LIMITATIONS: Bipolar depressive patients received treatment of benzodiazepines, which may confound the findings. CONCLUSIONS: Our results illustrated that connectivity disturbances in the language regions may change depending on the disease phase of bipolar disorder. PMID- 26991368 TI - Computer- or web-based interventions for perinatal mental health: A systematic review. AB - BACKGROUND: Treating prenatal mental health issues is of great importance, but access to treatment is often poor. One way of accessing treatment is through computer- or web-based interventions. Reviews have shown that these interventions can be effective for a variety of mental health disorder across different populations. However, their effectiveness for women in the perinatal period has not been reviewed. This review therefore aimed to provide a first overview of computer- or web-based interventions for women's perinatal mental health issues by systematically identifying and reviewing their characteristics and efficacy. METHODS: Twelve electronic databases were searched for published and unpublished literature using keywords, supplemented by hand searches. Data were extracted for characteristics of the intervention and the study, study findings and the methodological quality was assessed. RESULTS: The majority of the eleven eligible studies were randomized controlled trials. Interventions were targeted at depression, stress, and complicated grief during the antenatal or postpartum period or the time after pregnancy loss. Findings suggest that computer- or web based interventions targeted at improving mental health, especially depression and complicated grief, may be effective. LIMITATIONS: Findings and their generalizability is limited by the heterogeneity of reviewed interventions and study designs, as well as methodological limitations. CONCLUSIONS: This systematic review constitutes the first synthesis of research on computer- or web based interventions for perinatal mental health issues and provides preliminary support that this could be a promising form of treatment during this period. However, there are significant gaps in the current evidence-base so further research is needed. PMID- 26991367 TI - Longitudinal course of ante- and postpartum generalized anxiety symptoms and associated factors in West-African women from Ghana and Cote d'Ivoire. AB - BACKGROUND: Little is known about the course of perinatal anxiety, particularly in low and middle income countries. This study aimed at examining trajectories of ante- and postpartum generalized anxiety symptoms in West-African women and their associations with mother and child characteristics. METHODS: 778 women from Cote d'Ivoire and Ghana were investigated between 04/2010 and 03/2014. Anxiety symptoms were measured using the seven-item Generalized Anxiety Disorder scale (GAD-7) at three months antepartum and three, 12 and 24 months postpartum. Growth mixture modeling was applied to identify latent trajectory classes of anxiety. Multinomial logistic regression was used to investigate the associations of psychosocial, sociodemographic, obstetric and clinical characteristics with different trajectories. RESULTS: Four distinct trajectories of anxiety were identified. The majority of women (79.8%) had consistent low anxiety symptoms, while 11.4% had elevated anxiety scores before and around childbirth that decreased gradually. 5.4% of women showed increasing anxiety symptoms over time. Few women (3.3%) had transient anxiety with elevated scores at three and 12 months postpartum. Risk factors for elevated anxiety levels around childbirth were antepartum depressive symptoms, higher levels of stress (economic, marital and social stress), lower child birth weight, and multiparity. Partner support was found to be protective. LIMITATIONS: Anxiety symptoms were assessed using a screening instrument and not through a formal diagnostic classification system. Some putative risk factors were not investigated, and some psychosocial factors were assessed retrospectively. CONCLUSION: The presence of different trajectories underline the importance of monitoring anxiety symptoms in pregnant women and in mothers with infants/toddlers. PMID- 26991370 TI - Environmental and genetic determinants of childhood depression: The roles of DAT1 and the antenatal environment. AB - Research on adolescent and adult populations has linked depression to variation in several monoaminergic genes, but genetic association studies on depression in children are limited. Additionally, few studies have investigated whether stressors occurring very early in development moderate the influence of certain genes on depression. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) from monoaminergic genes interacted with measures of early life stress to influence depressive symptoms in children. Participants were members of the Auckland Birthweight Collaborative cohort. Small for gestational age (SGA) and maternal stress during pregnancy were measured at birth and used as indicators of early life stress. At age 11, depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and DNA samples were collected for genotyping. A two-way ANOVA revealed that SGA and a SNP from the dopamine transporter gene DAT1 had an interactive effect on children's depressive symptoms. Specifically, symptoms were greater in children born SGA who are T homozygous for the rs1042098 SNP. These findings suggest that adverse intrauterine environments leading to low birth weight also seem to exacerbate the effects of certain DAT1 variants on depression. PMID- 26991369 TI - Classification of facial expressions of emotion and risk for suicidal ideation in children of depressed mothers: Evidence from cross-sectional and prospective analyses. AB - BACKGROUND: Despite the increased risk for suicidal ideation (SI) in children of mothers with a history of major depressive disorder (MDD), little is known about specific risk factors for SI in these children. The present study is the first to our knowledge to examine the potential role of biases in the identification of facial expressions of emotion. METHODS: Participants were 202 children (aged 8-14 years) and their mothers (aged 24-55 years) that comprised three groups based on maternal history of MDD and children's history of SI: Mom MDD/Child SI (n=35); Mom MDD/No Child SI (n=76); and Controls (i.e., no mom MDD and no child SI; n=91). RESULTS: We found that children in the Mom MDD/Child SI group were more likely to misclassify full-intensity angry emotions as sad than children in the other groups. Among children in the two mother MDD groups, both the overall proportion of full-intensity angry emotions misclassified and the proportion of full-intensity angry emotions misclassified specifically as sad predicted the occurrence of SI over a 2-year follow-up, even after accounting for the impact of children's own diagnoses of MDD during the follow up. LIMITATIONS: Our findings might not generalize to other negative emotions, such as fear or disgust. CONCLUSION: This highlights specific emotion identification abnormalities that could be targeted in early suicide prevention efforts and suggests that these abnormalities are at least partially independent of children's risk for MDD. PMID- 26991371 TI - Influence of spatial frequency and emotion expression on face processing in patients with panic disorder. AB - BACKGROUND: Deficits in facial emotion processing is a major characteristic of patients with panic disorder. It is known that visual stimuli with different spatial frequencies take distinct neural pathways. This study investigated facial emotion processing involving stimuli presented at broad, high, and low spatial frequencies in patients with panic disorder. METHODS: Eighteen patients with panic disorder and 19 healthy controls were recruited. Seven event-related potential (ERP) components: (P100, N170, early posterior negativity (EPN); vertex positive potential (VPP), N250, P300; and late positive potential (LPP)) were evaluated while the participants looked at fearful and neutral facial stimuli presented at three spatial frequencies. RESULTS: When a fearful face was presented, panic disorder patients showed a significantly increased P100 amplitude in response to low spatial frequency compared to high spatial frequency; whereas healthy controls demonstrated significant broad spatial frequency dependent processing in P100 amplitude. Vertex positive potential amplitude was significantly increased in high and broad spatial frequency, compared to low spatial frequency in panic disorder. Early posterior negativity amplitude was significantly different between HSF and BSF, and between LSF and BSF processing in both groups, regardless of facial expression. LIMITATION: The possibly confounding effects of medication could not be controlled. CONCLUSIONS: During early visual processing, patients with panic disorder prefer global to detailed information. However, in later processing, panic disorder patients overuse detailed information for the perception of facial expressions. These findings suggest that unique spatial frequency-dependent facial processing could shed light on the neural pathology associated with panic disorder. PMID- 26991372 TI - The impact of subdividing the "atypical" category for urinary cytology on patient management. AB - INTRODUCTION: The purpose of the study is to determine the impact of subdividing the "atypical" cytology interpretation into two groups: Atypical urothelial cells of uncertain significance (AUC-US) and Atypical urothelial cells suspicious for high-grade urothelial carcinoma (AUC-H/SHGUC), on management of patients with no prior history of UC. MATERIALS AND METHOD: This is a retrospective study of "atypical" urine cytology with subsequent tissue examination occurring within six months. Cytology reports with "atypical" interpretation were reclassified into AUS-UC and AUC-H based on morphologic features identified by the Johns Hopkins system and the Paris system for urine cytology. Follow-up and categorical outcomes were compared between the reclassified AUC-US and AUC-H groups. RESULTS: There was no significant difference (P < 0.4539) in the rate of cytology follow up, the follow-up cytology result (P < 0.1845), or time between follow-up cytologies (P < 0.0869) between the reclassified atypical group of AUC-H and AUC US. There was a significant association (P < 0.0001) of rate of malignancy with the reclassified AUC-H (87.18%) compared to the AUC-US (58.68%) groups. CONCLUSION: There was no difference in follow-up between the AUC-H and AUC-US, however there was a difference in the rates of malignancy in the two groups. The AUC-H group is similar to the SHGUC group of the Paris system and can be considered as such, whereas the AUC-US group should continue to be considered atypical. We conclude that reclassification of the "atypical" category into AUC US and AUC-H/SHGUC can reduce the rate of atypia and help in focused follow-up and targeted management. Diagn. Cytopathol. 2016;44:477-482. (c) 2016 Wiley Periodicals, Inc. PMID- 26991373 TI - The Effect of Hydrodynamic Slip on Membrane-Based Salinity-Gradient-Driven Energy Harvesting. AB - The effect of hydrodynamic slip on salinity-gradient-driven power conversion by the process of reverse electrodialysis, in which the free energy of mixing of salt and fresh water across a nanoporous membrane is harnessed to drive an electric current in an external circuit, is investigated theoretically using a continuum fluid dynamics model. A general one-dimensional model is derived that decouples transport inside the membrane pores from the effects of electrical resistance at the pore ends, from which an analytical expression for the power conversion rate is obtained for a perfectly ion-selective membrane as a function of the slip length, surface charge density, membrane thickness, pore radius, and other membrane and electrolyte properties. The theoretical model agrees quantitatively with finite-element numerical calculations and predicts significant enhancements--up to several times--of salinity-gradient power conversion due to hydrodynamic slip for realistic systems. PMID- 26991374 TI - Quantitative analysis of short- and long-distance racing performance in young and adult horses and association analysis with functional candidate genes in Spanish Trotter horses. AB - The association of five candidate genes with sporting performance in young and adult Spanish Trotter horses (STHs) was performed according to a previous selection based on quantitative analysis of the trait time per kilometre (TPK). A total of 334 516 records of TPK from 5958 STHs were used to estimate the estimated breeding values (EBVs) at different age groups (young and adults horses) throughout the range of distances (1600-2700 m) using a bicharacter random regression model. The heritability estimated by distance ranged from 0.16 to 0.40, with a different range for the two age groups. Considering the animals with the best and the worst deregressed EBV, 321 STHs were selected for SNP genotyping in MSTN, COX4I2, PDK4, DMRT3 and CKM genes. An association analysis based on ridge and logistic regression revealed that the young trotters with genotype GG in PDK4 (p < 0.05) and AA of DMRT3 (p < 0.001) SNPs show the best potential in short-distance races, while those carrying the genotype AA in DMRT3 (p < 0.001) and CC in CKM (p < 0.05) genes seem to be the best in long-distance races. Adult trotters with genotype AA in DMRT3 also display greater speed (p < 0.05) and endurance (p < 0.001). PMID- 26991375 TI - Intravenous fluid management in critically ill patients: for everybody or for a dedicated team? PMID- 26991376 TI - NO synthase inhibition attenuates EDHF-mediated relaxation induced by TRPV4 channel agonist GSK1016790A in the rat pulmonary artery: Role of TxA2. AB - BACKGROUND: The aim of the present study was to observe the concomitant activation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways by TRPV4 channel agonist GSK1016790A in the rat pulmonary artery and explore the mechanism by which NO synthase inhibition attenuates EDHF mediated relaxation in endothelium-intact rat pulmonary artery. METHODS: Tension experiments were conducted on the pulmonary artery from male Wistar rats. RESULTS: TRPV4 channel agonist GSK1016790A (GSK) caused concentration-dependent relaxation (Emax 86.9+/-4.6%; pD2 8.7+/-0.24) of the endothelium-intact rat pulmonary artery. Combined presence of apamin and TRAM-34 significantly attenuated the relaxation (Emax 61.1+/-6.0%) to GSK. l-NAME (100MUM) significantly attenuated (8.2+/-2.9%) the relaxation response to GSK that was resistant to apamin plus TRAM-34. However, presence of ICI192605 or furegrelate alongwith l-NAME revealed the GSK-mediated EDHF-response (Emax of 28.5+/-5.2%; Emax 24.5+/-4.3%) in this vessel, respectively. Further, these two TxA2 modulators (ICI/furegrelate) alongwith l-NAME had no effect on SNP-induced endothelium-independent relaxation in comparison to l-NAME alone. This EDHF mediated relaxation was sensitive to inhibition by K(+) channel blockers apamin and TRAM-34 or 60mMK(+) depolarizing solution. Further, combined presence of apamin and TRAM-34 in U46619 pre-contracted pulmonary arterial rings significantly reduced the maximal relaxation (Emax 71.6+/-6.9%) elicited by GSK, but had no effect on the pD2 (8.1+/-0.03) of the TRPV4 channel agonist in comparison to controls (Emax, 92.4+/-4.3% and pD2, 8.3+/-0.06). CONCLUSION: The present study suggests that NO and EDHF are released concomitantly and NO synthase inhibition attenuates GSK-induced EDHF response through thromboxane pathway in the rat pulmonary artery. PMID- 26991377 TI - Acute treatment with doxorubicin induced neurochemical impairment of the function of dopamine system in rat brain structures. AB - BACKGROUND: The clinical studies have shown that chemotherapy may impair cognitive functions especially in the patients treated for breast cancer. It should be mention that only few studies have made use of animals to investigate the effects of chemotherapy on the brain function. Doxorubicin (Adriamycin) is an anthracycline antibiotic commonly used for chemotherapy of breast cancer. METHODS: This study examined the effect of doxorubicin (1.5 and 3.0mg/kg ip) after acute administration on the levels of dopamine, noradrenaline, serotonin and their metabolites in the rat brain structures connected with cognition and psychiatric disorders. RESULTS: The data indicate that doxorubicin produced a significant and specific for the dopamine system inhibition of its activity in the investigated structures connected with the fall of dopamine concentration (decrease from 25 to 30% in the frontal cortex; from 30 to 60% in the hippocampus and about 20% of the control in the striatum, p<0.05) and its extraneuronal metabolite, 3-MT (from 35% in the frontal cortex to 60% in the hippocampus of the control level, p<0.01). However, doxorubicin did not affect others monoaminergic transmitters in the brain: noradrenaline and serotonin. CONCLUSION: Summing up, these data indicate that a single injection of doxorubicin produced a clear and significant inhibition of dopamine system activity in all investigated structures with the strongest effect in the hippocampus what may lead to the disturbances of the cognitive functions at the patients treated for cancer. Moreover, such treatment did not significantly affect others monoaminergic transmitters such as noradrenaline and serotonin. PMID- 26991378 TI - Fungal treatment for the removal of antibiotics and antibiotic resistance genes in veterinary hospital wastewater. AB - The emergence and spread of antibiotic resistance represents one of the most important public health concerns and has been linked to the widespread use of antibiotics in veterinary and human medicine. The overall elimination of antibiotics in conventional wastewater treatment plants is quite low; therefore, residual amounts of these compounds are continuously discharged to receiving surface waters, which may promote the emergence of antibiotic resistance. In this study, the ability of a fungal treatment as an alternative wastewater treatment for the elimination of forty-seven antibiotics belonging to seven different groups (beta-lactams, fluoroquinolones, macrolides, metronidazoles, sulfonamides, tetracyclines, and trimethoprim) was evaluated. 77% of antibiotics were removed after the fungal treatment, which is higher than removal obtained in conventional treatment plants. Moreover, the effect of fungal treatment on the removal of some antibiotic resistance genes (ARGs) was evaluated. The fungal treatment was also efficient in removing ARGs, such as ermB (resistance to macrolides), tetW (resistance to tetracyclines), blaTEM (resistance to beta-lactams), sulI (resistance to sulfonamides) and qnrS (reduced susceptibility to fluoroquinolones). However, it was not possible to establish a clear link between concentrations of antibiotics and corresponding ARGs in wastewater, which leads to the conclusion that there are other factors that should be taken into consideration besides the antibiotic concentrations that reach aquatic ecosystems in order to explain the emergence and spread of antibiotic resistance. PMID- 26991379 TI - Uptake of 8:2 perfluoroalkyl phosphate diester and its degradation products by carrot and lettuce from compost-amended soil. AB - The present work studied the uptake of 8:2 perfluoroalkyl phosphate diester (diPAP) by two different crops (lettuce and carrot) and two different amended soils. Firstly, the possible degradation of 8:2 diPAP in the absence of crop was studied and 8:2 monoPAP (monophosphate), 8:2 FTCA (saturated fluorotelomer carboxylate), 8:2 FTUCA (unsaturated fluorotelomer carboxylate), 7:3 FTCA (saturated fluorotelomer carboxylate), PFHpA (perfluoroheptanoic acid), PFHxA (perfluorohexanoic acid) and PFOA (perfluorooctanoic acid) were detected. In the presence of crops, different degradation products were detected in the soil and, while PFNA (perfluorononanoic acid), PFHpA, PFHxA, PFPeA (perfluoropentacoic acid), PFBA (perfluorobutanoic acid), 7:3 FTCA and PFOA were determined in the cultivation media when carrot was grown, PFOA was the only degradation product detected in the case of lettuce experiments. Regarding the uptake in carrot, all the degradation products except 7:3 FTCA were translocated from the soil to the carrot. Carrot core, peel and leaves bioconcentration factors, BCFs, were determined for 8:2 diPAP and its degradation products. Values lower than method detection limits for core and low BCFs in peel (0.025-0.042) and leaves (0.028 0.049) were achieved for 8:2 diPAP. Regarding to the degradation products, the higher their water solubility, the higher the plant translocation. In this sense, the lower the carbon chain length of PFCAs, the higher the BCFs determined (PFBA > PFHxA > PFHpA > PFOA > PFNA). In general, lower total BCFs were achieved when the total organic carbon of the soils increased. For lettuce experiments, 8:2 diPAP (0.04-0.18) and PFOA (0.28-1.57) were only determined in lettuce heart. PMID- 26991381 TI - Assessment of water quality and genotoxic impact by toxic metals in Geophagus brasiliensis. AB - This study used the pearl cichlid Geophagus brasiliensis as a bioindicator to survey the health of the aquatic environment on four sites (P1, P2, P3 and P4) of the Mumbuca stream located at Monte Carmelo/MG, Brazil. The selection of different sites was made with reference to the gradient of urban activity and via physicochemical and biological evaluation of water quality and genotoxicity. The water quality index was classified as 'good' for P1 and P4, regular in P2 and 'poor' for P3. The micronuclei (MN) frequency obtained from blood analysis was in agreement with the water quality, such that the higher values of MN were detected in sites evaluated as poor. Water degradation conditions worsen according to the flow of the stream over the sites P1, P2 and P3, but for site P4, located after the Monte Carmelo Sewage Treatment Plant, improvements in the micronuclei frequency are detected. Our results showed high levels of potentially toxic metals (chromium, lead, aluminum and nickel) in specific stream sites (P2 and P3). We suggest that the micronuclei induction in G. brasiliensis could be due to the presence of these compounds. PMID- 26991380 TI - Toxaphene levels in retail food from the Pearl River Delta area of South China and an assessment of dietary intake. AB - Limited literature exists on toxaphene contamination in food worldwide, particularly in mainland China. In this study, three toxaphene congeners, Parlar 26 (B8-1413), Parlar 50 (B9-1679) and Parlar 62 (B9-1025), were analyzed in five different food categories from the Pearl River Delta Area in China using isotope dilution high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS), and toxaphene levels in food were reported and toxaphene dietary intake by local residents estimated. The results showed that fish contained the highest toxaphene level with a median of 12.87 pg/g wet weight (ww), followed by poultry meat, egg products, livestock meat and vegetable, which had median levels of 5.8, 2.2, 1.89 and 0.67 pg/g ww, respectively. Parlar 50 and Parlar 26 were the predominant characteristic congeners in fish, and Parlar 26 was the predominant congener not only in poultry products and eggs, but also in livestock and vegetable. The estimated average daily intake found by local residents was 35.57 pg/kg body weight/day. Overall toxaphene levels and estimated dietary intake in the Pearl River Delta Area of South China are far lower than the European Maximum Residue Limits (EU MRLs), the German MRL for fish, and other international literature data. Therefore, the risk of adverse health effects from dietary intakes of toxaphene for the local residents is not considerable at the current time, but follow-ups are warranted to study dynamic changes of toxaphene in food in this area. PMID- 26991382 TI - Characteristics and DBP formation of dissolved organic matter from leachates of fresh and aged leaf litter. AB - Dissolved organic matter (DOM) was leached from leaves of two trees commonly grown in subtropical regions, Pinus elliottii (commonly known as slash pine) and Schima superba (S. superba), and its degradation pattern and potential for forming disinfection byproducts (DBPs) were evaluated. The leaves were exposed in the field for up to one year before leaching. The DOM leached from slash pine litter contained on average 10.4 mg of dissolved organic carbon (DOC) per gram of dry weight; for S. superba the average was 37.2 mg-DOC/g-dry weight. Ultraviolet and visible light absorbance, fluorescence, and molecular weight analysis indicated that more aromatic/humic and higher molecular weight compounds are formed as leaf litter ages. A 4-component parallel factor analysis of the fluorescence data showed that the intensity of peaks related with protein-like components decreased gradually during biodegradation, while that of peaks attributed to humic-acid-like components increased continuously. Fresh slash pine leachates formed on average 40.0 MUg of trihalomethane (THM) per milligram of DOC, while S. superba leachates formed 45.6 MUg. THM formation showed peak values of 55.7 MUg/mg DOC for slash pine and 74.9 MUg/mg DOC for S. superba after 8 months of aging. The formation of haloacetonitrile (HAN) and trichloronitromethane (TCNM) increased with increasing leaf age, while chloral hydrate (CH) formation did not show such a trend. Specific UV absorbance showed some positive correlation with DBPs, but humic-acid-like and protein-like absorbance peaks correlated with CH and TCNM yields in only some leaf samples. PMID- 26991383 TI - Rapid methodology to screen flame retardants in upholstered furniture for compliance with new California labeling law (SB 1019). AB - In response to concerns regarding the widespread use of flame retardants, the California Legislature passed a law (SB1019) requiring labels on furniture products to indicate whether they do or do not contain flame retardants. To support the enforcement of the new law, our laboratory developed a step-wise, screening approach to test for brominated (BFR) and phosphorus-based flame retardants (OPFRs) in several types of furniture components (foam, fabric, batting, plumage, etc.). We used X-Ray Fluorescence (XRF) to screen for the presence of Br (and other elements) and Inductively Coupled Plasma - Optical Emission Spectrometry (ICP-OES) to identify and measure the concentration of P (and other elements). The same samples were also extracted by dichloromethane using sonication and analyzed by a single injection into a Gas Chromatograph - Tandem Mass Spectrometer to obtain concentrations of specific BFRs and OPFRs. Our approach showed excellent screening potential for Br and Sb by XRF and for P by ICP-OES, with both tests having predictive values of a negative equal to 1. To explore and screen for flame retardants in products not included in our current list of target chemicals, we used Liquid Chromatography/Time-of-Flight Mass Spectrometry operated with electrospray ionization, to identify additional flame retardants to be incorporated in quantitative methods. We are making all our methodologies public to facilitate simple and low cost methods that can help manufacturers and suppliers have their products tested and correctly labeled, ultimately benefitting the consumer. PMID- 26991384 TI - Resecting critical nodes from an epileptogenic circuit in refractory focal-onset epilepsy patients using subtraction ictal SPECT coregistered to MRI. AB - OBJECTIVE The purpose of this study was to assess the positive predictive value of postresection outcomes obtained by presurgical subtracted ictal SPECT in patients with lesional (MRI positive) and nonlesional (MRI negative) refractory extratemporal lobe epilepsy (ETLE) and temporal lobe epilepsy (TLE). Specifically, outcomes were compared between partial versus complete resection of the regions of transient hyperperfusion identified using subtraction ictal SPECT coregistered to MRI (SISCOM) in relation to the ictal onset zone (IOZ) that was confirmed by electrocorticography (ECoG). That is, SISCOM was used to understand the long-term postsurgical outcomes following resection of the IOZ that overlapped with 1 or more regions of ictal onset-associated transient hyperperfusion. METHODS The study cohort included 44 consecutive patients with refractory ETLE or TLE who were treated between 2002 and 2013 and underwent presurgical evaluation using SISCOM. Concordance was determined between SISCOM localization and the IOZ on the basis of ECoG monitoring. In addition, the association between the extent of the resection site overlapping with the SISCOM signal and postresection outcomes were assessed. Postsurgical follow-up was longer than 24 months in 39 of 44 patients. RESULTS The dominant SISCOM signals were concordant with ECoG and overlapped the resection site in 32 of 44 (73%) patients (19 ETLE and 13 TLE patients), and 20 of 32 (63%) patients became seizure free. In all 19 ETLE patients with concordant SISCOM and ECoG results, the indicated location of ictal onset on ECoG was completely resected; 11 of 19 patients (58%) became seizure free (Engel Class I). In all 13 TLE patients with concordant SISCOM and ECoG results, the indicated ECoG focus was completely resected; 9 of 13 patients (69%) became seizure free (Engel Class I). Complete resection of the SISCOM signal was found in 7 of 34 patients (21%). Of these 7 patients, 5 patients (72%) were seizure free (Engel Class I). Partial resection of the SISCOM signal was found in 16 of 34 patients (47%), and 10 of these 16 patients (63%) were seizure free (Engel Class I) after more than 24 months of follow-up. CONCLUSIONS Concordance between 1 or more SISCOM regions of hyperperfusion with ECoG and at least partial resection of the dominant SISCOM signal in this refractory epilepsy cohort provided additional useful information for predicting long-term postresection outcomes. Such regions are likely critical nodes in more extensive, active, epileptogenic circuits. In addition, SPECT scanner technology may limit the sensitivity of meaningful SISCOM signals for identifying the maximal extent of the localizable epileptogenic network. PMID- 26991385 TI - Editorial: Passive language mapping. PMID- 26991386 TI - Passive language mapping combining real-time oscillation analysis with cortico cortical evoked potentials for awake craniotomy. AB - OBJECTIVE Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of "passive" mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors. METHODS Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated. RESULTS Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively. CONCLUSIONS The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain. PMID- 26991387 TI - A randomized controlled trial comparing autologous cranioplasty with custom-made titanium cranioplasty. AB - OBJECTIVE Autologous bone is usually used to reconstruct skull defects following decompressive surgery. However, it is associated with a high failure rate due to infection and resorption. The aim of this study was to see whether it would be cost-effective to use titanium as a primary reconstructive material. METHODS Sixty-four patients were enrolled and randomized to receive either their own bone or a primary titanium cranioplasty. All surgical procedures were performed by the senior surgeon. Primary and secondary outcome measures were assessed at 1 year after cranioplasty. RESULTS There were no primary infections in either arm of the trial. There was one secondary infection of a titanium cranioplasty that had replaced a resorbed autologous cranioplasty. In the titanium group, no patient was considered to have partial or complete cranioplasty failure at 12 months of follow-up (p = 0.002) and none needed revision (p = 0.053). There were 2 deaths unrelated to the cranioplasty, one in each arm of the trial. Among the 31 patients who had an autologous cranioplasty, 7 patients (22%) had complete resorption of the autologous bone such that it was deemed a complete failure. Partial or complete autologous bone resorption appeared to be more common among young patients than older patients (32 vs 45 years old, p = 0.013). The total cumulative cost between the 2 groups was not significantly different (mean difference A$3281, 95% CI $-9869 to $3308; p = 0.327). CONCLUSIONS Primary titanium cranioplasty should be seriously considered for young patients who require reconstruction of the skull vault following decompressive craniectomy. Clinical trial registration no.: ACTRN12612000353897 ( anzctr.org.au ). PMID- 26991388 TI - Walking assessment after lumbar puncture in normal-pressure hydrocephalus: a delayed improvement over 3 days. AB - OBJECTIVE The determination of gait improvement after lumbar puncture (LP) in idiopathic normal-pressure hydrocephalus (iNPH) is crucial, but the best time for such an assessment is unclear. The authors determined the time course of improvement in walking after LP for single-task and dual-task walking in iNPH. METHODS In patients with iNPH, sequential recordings of gait velocity were obtained prior to LP (time point [TP]0), 1-8 hours after LP (TP1), 24 hours after LP (TP2), 48 hours after LP (TP3), and 72 hours after LP (TP4). Gait analysis was performed using a pressure-sensitive carpet (GAITRite) under 4 conditions: walking at preferred velocity (STPS), walking at maximal velocity (STMS), walking while performing serial 7 subtractions (dual-task walking with serial 7 [DTS7]), and walking while performing verbal fluency tasks (dual-task walking with verbal fluency [DTVF]). RESULTS Twenty-four patients with a mean age of 76.1 +/- 7.8 years were included in this study. Objective responder status moderately coincided with the self-estimation of the patients with subjective high false positive results (83%). The extent of improvement was greater for single-task walking than for dual-task walking (p < 0.05). Significant increases in walking speed were found at TP2 for STPS (p = 0.042) and DTVF (p = 0.046) and at TP3 for STPS (p = 0.035), DTS7 (p = 0.042), and DTVF (p = 0.044). Enlargement of the ventricles (Evans Index) positively correlated with early improvement. Gait improvement at TP3 correlated with the shunt response in 18 patients. CONCLUSIONS Quantitative gait assessment in iNPH is important due to the poor self-evaluation of the patients. The maximal increase in gait velocity can be observed 24-48 hours after the LP. This time point is also best to predict the response to shunting. For dual-task paradigms, maximal improvement appears to occur later (48 to 72 hours). Assessment of gait should be performed at Day 2 or 3 after LP. PMID- 26991389 TI - Letter to the Editor: Transsphenoidal surgery for nonfunctioning adenomas. PMID- 26991391 TI - Fracture and migration of a retained wire into the thoracic cavity after endovascular neurointervention: report of 2 cases. AB - Although extremely rare, retention of foreign bodies such as microcatheters or micro guidewires can occur during various neurovascular procedures due to gluing of the microcatheter tip or entanglement of the micro guidewire tip with intravascular devices. The authors have experienced 2 cases of irresolvable wire retention, one after flow diverter placement for a left cavernous internal carotid artery aneurysm and the other after intracranial stenting for acute basilar artery occlusion. The first patient presented 6 weeks after her procedure with right lung parenchymal hemorrhage due to direct piercing of the lung parenchyma after the retained wire fractured and migrated out of the aortic arch. The second patient presented 4 years after his procedure with pneumothorax due to migration of the fractured guidewire segment into the right thoracic cavity. In this report, the authors discuss the possible mechanisms of these unusual complications and how to prevent delayed consequences from a retained intravascular metallic wire. PMID- 26991390 TI - Endosphenoidal coil for intraoperative magnetic resonance imaging of the pituitary gland during transsphenoidal surgery. AB - OBJECTIVE Pituitary MR imaging fails to detect over 50% of microadenomas in Cushing's disease and nearly 80% of cases of dural microinvasion. Surface coils can generate exceptionally high-resolution images of the immediately adjacent tissues. To improve imaging of the pituitary gland, a receive-only surface coil that can be placed within the sphenoid sinus (the endosphenoidal coil [ESC]) during transsphenoidal surgery (TSS) was developed and assessed. METHODS Five cadaver heads were used for preclinical testing of the ESC. The ESC (a double turn, 12-mm-diameter surface coil made from 1-mm-diameter copper wire) was developed to obtain images in a 1.5-T MR scanner. The ESC was placed (via a standard sublabial TSS approach) on the anterior sella face. Clinical MR scans were obtained using the 8-channel head coil and ESC as the receiver coils. Using the ESC, ultra-high-resolution, 3D, balanced fast field echo (BFFE) and T1 weighted imaging were performed at resolutions of 0.25 * 0.25 * 0.50 mm3 and 0.15 * 0.15 * 0.30 mm3, respectively. RESULTS Region-of-interest analysis indicated a 10-fold increase in the signal-to-noise ratio (SNR) of the pituitary when using the ESC compared with the 8-channel head coil. ESC-related improvements (p < 0.01) in the SNR were inversely proportional to the distance from the ESC tip to the anterior pituitary gland surface. High-resolution BFFE MR imaging obtained using ESC revealed a number of anatomical features critical to pituitary surgery that were not visible on 8-channel MR imaging, including the pituitary capsule, the intercavernous sinus, and microcalcifications in the pars intermedia. These ESC imaging findings were confirmed by the pathological correlation with whole mount pituitary sections. CONCLUSIONS ESC can significantly improve SNR in the sellar region intraoperatively using current 1.5-T MR imaging platforms. Improvement in SNR can provide images of the sella and surrounding structures with unprecedented resolution. Clinical use of this ESC may allow for MR imaging detection of previously occult pituitary adenomas and identify microscopic invasion of the dura or cavernous sinus. PMID- 26991392 TI - Tensor SOM and tensor GTM: Nonlinear tensor analysis by topographic mappings. AB - In this paper, we propose nonlinear tensor analysis methods: the tensor self organizing map (TSOM) and the tensor generative topographic mapping (TGTM). TSOM is a straightforward extension of the self-organizing map from high-dimensional data to tensorial data, and TGTM is an extension of the generative topographic map, which provides a theoretical background for TSOM using a probabilistic generative model. These methods are useful tools for analyzing and visualizing tensorial data, especially multimodal relational data. For given n-mode relational data, TSOM and TGTM can simultaneously organize a set of n-topographic maps. Furthermore, they can be used to explore the tensorial data space by interactively visualizing the relationships between modes. We present the TSOM algorithm and a theoretical description from the viewpoint of TGTM. Various TSOM variations and visualization techniques are also described, along with some applications to real relational datasets. Additionally, we attempt to build a comprehensive description of the TSOM family by adapting various data structures. PMID- 26991394 TI - Vascular responses to compound 48/80 in rat mesenteric vascular beds. AB - A further investigation was performed on the vascular effect of endogenous histamine using the histamine releaser, compound 48/80, in rat mesenteric vascular beds with active tone. In preparations with intact endothelium, low concentrations of compound 48/80 (1.53 * 10(-5) - 3 * 1.53 * 10(-5) mg/mL) perfusion for 1 min only induced a small vasodilation. High concentrations of compound 48/80 (1.53 * 10(-4) - 3 * 1.53 * 10(-2) mg/mL) induced a biphasic vascular responses, an initial vasoconstriction followed a subsequent long lasting vasodilation. The vasodilation induced by low concentrations of compound 48/80 and the vasoconstriction induced by high concentration of compound 48/80 was inhibited by olopatadine. However, cimetidine did not affect the responses induced by compound 48/80. Endothelium removal enlarged the compound 48/80 induced phase-2 vasoconstriction, while it attenuated the phase-3 vasodilation. Additionally, indomethacin and seratrodast significantly inhibited vasoconstriction but it did not affect the long-lasting vasodilation induced by high concentrations of compound 48/80. Ruthenium red inhibited the vasodilation induced by low concentrations and high concentrations of compound 48/80. These results suggest that the vasoconstriction induce by high concentrations of compound 48/80 is mediated by endogenous histamine released from mast cells. It is also suggested that thromboxane A2 released from mast cells is related to the vasoconstriction. PMID- 26991393 TI - Recommendations for Health Monitoring and Reporting for Zebrafish Research Facilities. AB - The presence of subclinical infection or clinical disease in laboratory zebrafish may have a significant impact on research results, animal health and welfare, and transfer of animals between institutions. As use of zebrafish as a model of disease increases, a harmonized method for monitoring and reporting the health status of animals will facilitate the transfer of animals, allow institutions to exclude diseases that may negatively impact their research programs, and improve animal health and welfare. All zebrafish facilities should implement a health monitoring program. In this study, we review important aspects of a health monitoring program, including choice of agents, samples for testing, available testing methodologies, housing and husbandry, cost, test subjects, and a harmonized method for reporting results. Facilities may use these recommendations to implement their own health monitoring program. PMID- 26991395 TI - The broadly effective recessive resistance gene xa5 of rice is a virulence effector-dependent quantitative trait for bacterial blight. AB - Mutations in disease susceptibility (S) genes, here referred to as recessive resistance genes, have promise for providing broad durable resistance in crop species. However, few recessive disease resistance genes have been characterized. Here, we show that the broadly effective resistance gene xa5,for resistance to bacterial blight of rice (Oryza sativa), is dependent on the effector genes present in the pathogen. Specifically, the effectiveness of xa5 in preventing disease by strains of Xanthomonas oryzae pv. oryzae is dependent on major transcription activation-like (TAL) effector genes, and correlates with reduced expression of the cognate S genes. xa5 is ineffective in preventing disease by strains containing the TAL effector gene pthXo1, which directs robust expression of the S gene OsSWEET11, a member of sucrose transporter gene family. Incompatibility is associated with major TAL effectors that target the known alternative S genes OsSWEET14 and OsSWEET13. Incompatibility is defeated by transfer of pthXo1 to otherwise xa5-incompatible strains or by engineering a synthetic designer TAL effector to boost SWEET gene expression. In either case, compatible or incompatible, target gene expression and lesion formation are reduced in the presence of xa5. The results indicate that xa5 functions as a quantitative trait locus, dampening effector function, and, regardless of compatibility, target gene expression. Resistance is hypothesized to occur when S gene expression, and, by inference, sucrose leakage, falls below a threshold level. PMID- 26991396 TI - Schizophrenia risk variants in ITIH4 and CALN1 regulate gene expression in the dorsolateral prefrontal cortex. PMID- 26991397 TI - Melatonin receptor 1B gene associated with hyperglycemia in bipolar disorder. AB - Bipolar patients are at a higher risk of developing metabolic disorders. Cardiovascular morbidity and mortality is twice the rate reported in the population. Antipsychotic medication increases the risk of metabolic abnormalities. However, bipolar disorder and schizophrenia have a similarly increased mortality from cardiovascular causes of death, although bipolar patients medicate with antipsychotic drugs to a much smaller extent than schizophrenic patients. Bipolar disorder and schizophrenia share substantial genetic risk components; thus, increased metabolic abnormalities is hypothesized to be an effect of specific sets of metabolic risk genes, which might overlap with the metabolic risk genes in schizophrenia. This study reports that a functional genetic variant of MTNR1B, previously implicated in the impairment of glucose-stimulated insulin release also in schizophrenia, was associated with elevated fasting glucose levels in bipolar patients and controls. This finding suggests that the MTNR1B-dependent vulnerability for elevated fasting plasma glucose levels is shared between bipolar disorder and schizophrenia. PMID- 26991398 TI - Chromophore Structure of Photochromic Fluorescent Protein Dronpa: Acid-Base Equilibrium of Two Cis Configurations. AB - Dronpa is a novel photochromic fluorescent protein that exhibits fast response to light. The present article is the first report of the resonance and preresonance Raman spectra of Dronpa. We used the intensity and frequency of Raman bands to determine the structure of the Dronpa chromophore in two thermally stable photochromic states. The acid-base equilibrium in one photochromic state was observed by spectroscopic pH titration. The Raman spectra revealed that the chromophore in this state shows a protonation/deprotonation transition with a pKa of 5.2 +/- 0.3 and maintains the cis configuration. The observed resonance Raman bands showed that the other photochromic state of the chromophore is in a trans configuration. The results demonstrate that Raman bands selectively enhanced for the chromophore yield valuable information on the molecular structure of the chromophore in photochromic fluorescent proteins after careful elimination of the fluorescence background. PMID- 26991399 TI - Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype. AB - BACKGROUND: Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype. AIM: To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype. METHODS: Twenty-eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty-four-hour intragastric pH monitoring was performed on day 7 on each regimen. RESULTS: In the overall genotype group, pH >=4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype-dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily. CONCLUSION: Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively. PMID- 26991401 TI - Decision-making in early clinical drug development. AB - This paper illustrates an approach to setting the decision framework for a study in early clinical drug development. It shows how the criteria for a go and a stop decision are calculated based on pre-specified target and lower reference values. The framework can lead to a three-outcome approach by including a consider zone; this could enable smaller studies to be performed in early development, with other information either external to or within the study used to reach a go or stop decision. In this way, Phase I/II trials can be geared towards providing actionable decision-making rather than the traditional focus on statistical significance. The example provided illustrates how the decision criteria were calculated for a Phase II study, including an interim analysis, and how the operating characteristics were assessed to ensure the decision criteria were robust. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991402 TI - Response Shifts in Depression Intervention for Early Adolescents. AB - OBJECTIVE: Patient-reported outcome measures are increasingly required as metrics for determining the efficacy of depression interventions. However, the scores obtained from self-reports over the course of treatment may be biased because respondents restructured the factors of the depression symptoms (reconceptualization), changed their values of the symptoms in reflecting depression (reprioritization), or adjusted their standards of assessing the levels of symptoms (recalibration). The aim of present study is to assess response shifts on the depression measure. METHOD: This study uses the procedures for assessing longitudinal measurement invariance to evaluate response shift effects on the Beck Depression Inventory II (BDI-II) with 320 early adolescents suffering from depression (43.8% boys and 56.2% girls) over the course of their treatment in the school settings. RESULTS: The findings reveal clear signs of response shifts (recalibration) in the BDI-II for depressed students. Compared with the factor scores before treatment, the factor scores after treatment were underestimated, especially on the negative attitude and performance difficulty factors. CONCLUSIONS: Estimates of treatment efficacy based on observed test scores appear to be confounded by response shifts. PMID- 26991403 TI - Early Recognition of and Intervention for Susac Syndrome in a Teenager With Encephalopathy. PMID- 26991400 TI - Uveal melanoma: From diagnosis to treatment and the science in between. AB - Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. (c) 2016 American Cancer Society. PMID- 26991404 TI - XPO1 Inhibition Preferentially Disrupts the 3D Nuclear Organization of Telomeres in Tumor Cells. AB - Previous work has shown that the three-dimensional (3D) nuclear organization of telomeres is altered in cancer cells and the degree of alterations coincides with aggressiveness of disease. Nuclear pores are essential for spatial genome organization and gene regulation and XPO1 (exportin 1/CRM1) is the key nuclear export protein. The Selective Inhibitor of Nuclear Export (SINE) compounds developed by Karyopharm Therapeutics (KPT-185, KPT-330/selinexor, and KPT-8602) inhibit XPO1 nuclear export function. In this study, we investigated whether XPO1 inhibition has downstream effects on the 3D nuclear organization of the genome. This was assessed by measuring the 3D telomeric architecture of normal and tumor cells in vitro and ex vivo. Our data demonstrate for the first time a rapid and preferential disruption of the 3D nuclear organization of telomeres in tumor cell lines and in primary cells ex vivo derived from treatment-naive newly diagnosed multiple myeloma patients. Normal primary cells in culture as well as healthy lymphocyte control cells from the same patients were minimally affected. Using both lymphoid and non-lymphoid tumor cell lines, we found that the downstream effects on the 3D nuclear telomere structure are independent of tumor type. We conclude that the 3D nuclear organization of telomeres is a sensitive indicator of cellular response when treated with XPO1 inhibitors. J. Cell. Physiol. 231: 2711-2719, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991405 TI - Embryos aggregation improves development and imprinting gene expression in mouse parthenogenesis. AB - Mouse parthenogenetic embryonic stem cells (PgESCs) could be applied to study imprinting genes and are used in cell therapy. Our previous study found that stem cells established by aggregation of two parthenogenetic embryos at 8-cell stage (named as a2 PgESCs) had a higher efficiency than that of PgESCs, and the paternal expressed imprinting genes were observably upregulated. Therefore, we propose that increasing the number of parthenogenetic embryos in aggregation may improve the development of parthenogenetic mouse and imprinting gene expression of PgESCs. To verify this hypothesis, we aggregated four embryos together at the 4-cell stage and cultured to the blastocyst stage (named as 4aPgB). qPCR detection showed that the expression of imprinting genes Igf2, Mest, Snrpn, Igf2r, H19, Gtl2 in 4aPgB were more similar to that of fertilized blastocyst (named as fB) compared to 2aPgB (derived from two 4-cell stage parthenogenetic embryos aggregation) or PgB (single parthenogenetic blastocyst). Post implantation development of 4aPgB extended to 11 days of gestation. The establishment efficiency of GFP-a4 PgESCs which derived from GFP-4aPgB is 62.5%. Moreover, expression of imprinting genes Igf2, Mest, Snrpn, notably downregulated and approached the level of that in fertilized embryonic stem cells (fESCs). In addition, we acquired a 13.5-day fetus totally derived from GFP-a4 PgESCs with germline contribution by 8-cell under zona pellucida (ZP) injection. In conclusion, four embryos aggregation improves parthenogenetic development, and compensates imprinting genes expression in PgESCs. It implied that a4 PgESCs could serve as a better scientific model applied in translational medicine and imprinting gene study. PMID- 26991406 TI - Correction: Enhanced photoresponse in dye-sensitized solar cells via localized surface plasmon resonance through highly stable nickel nanoparticles. AB - Correction for 'Enhanced photoresponse in dye-sensitized solar cells via localized surface plasmon resonance through highly stable nickel nanoparticles' by Md. Mahbubur Rahman et al., Nanoscale, 2016, DOI: 10.1039/c5nr08155f. PMID- 26991407 TI - Amount, Source, and Quality of Support as Predictors of Women's Birth Evaluations. AB - BACKGROUND: This paper examines the separate effects of the perceived amount, source, and quality of support during labor and delivery on women's positive and negative evaluations of their birth experiences. METHODS: Data come from the Listening to Mothers I and II (LTM) surveys (n = 2,765). Women's perception of support was regressed separately onto indices of positive and negative words that women associated with their labor and delivery. RESULTS: The total number of support sources, type of support person, and quality of support all impacted women's birth evaluations across different regression models, controlling for demographics, birth interventions, and other birth characteristics. Support overall had a greater effect on increasing women's positive evaluations, but was not as protective against negative evaluations. Support from medical and birth professionals (doctors, nurses, doulas) had the greatest effect on women's positive evaluations. Good partner support was complexly related: it was associated with less positive evaluations but also appeared to have a protective effect against negative birth evaluations. DISCUSSION: Support in childbirth is a complex concept with multiple dimensions that matter for women's birth evaluations. Support from nursing staff, doctors, and doulas is important for enabling positive evaluations while support from partners is more complexly related to women's evaluations. Research on support for laboring women should more extensively address the division of labor between different sources of support. PMID- 26991408 TI - Total Cell Number and its Allocation to Trophectoderm and Inner Cell Mass in In Vitro Obtained Cats' Blastocysts. AB - The aim of this study was to evaluate the developmental kinetics of cats' blastocysts in connection with their morphology and blastomeres allocation to trophoblast or embryoblast cells. We examined gross blastocyst morphology and the total number of blastomeres together with its allocation to inner cell mass (ICM) or trophectoderm (TE) cells in pre-implantation feline embryos obtained from 6th to 9th day of in vitro culture. From all the investigated embryos, 61.8% developed to early blastocyst, 37.4% to full and 7.6% to hatching blastocyst stage. The total cell number (TCN) varied form 58 cells in early day 6 to 245 in hatching day 8 blastocyst, with the mean 84.9 cells in early, 156.7 in full, and 204.4 in hatching ones. Day 8 blastocyst had the highest number of total cells, together with the highest mean number of ICM regardless of its morphological assessment. Early blastocyst (apart from day 6) had the highest number of arrested cells, while dead cells were the highest in full day 9 blastocyst. More data about the relationship between blastocyst development and morphology would facilitate the selection of optimal blastocysts for further procedures. PMID- 26991409 TI - Sevoflurane prevents stroke-induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I-dependent interaction between beta-arrestin 2 and extracellular signal-regulated kinases 1/2 in the rat hippocampus. AB - One of the most frequent psychological consequences of stroke is depression. Previous animal studies have demonstrated that post-conditioning with sevoflurane protects against focal cerebral ischemia and reperfusion injury. Thus, we hypothesized that repeated exposure to sevoflurane after transient ischemia can prevent the development of depressive-like behavior. To test this hypothesis, we induced transient cerebral ischemia via transient occlusion of bilateral common carotid arteries and examined the effects of subsequent repeated exposure to sevoflurane on sucrose preference, locomotor activity, and rearing activity in rats. To explore the putative neurobiological mechanisms, we further investigated the roles of hippocampal CB1 receptor in the behavioral effects of sevoflurane. We found that repeated sevoflurane exposures reversed ischemia-induced depressive like behaviors. Furthermore, CB1 receptor inhibition in the dorsal hippocampus (DH) abolished the effects of sevoflurane exposures on ischemia-induced depressive-like behaviors. In addition, repeated sevoflurane exposures increased CB1 receptor expression and endocannabinoids levels in the DH of ischemic rats. Moreover, repeated sevoflurane exposures enhanced the expression of beta-arrestin 2, increased the activation of extracellular signal-regulated kinases (ERK)1/2, and promoted the interaction of beta-arrestin 2 and ERK1/2 in the DH, and such effects were reversed by CB1 receptor antagonism in the DH. Finally, beta arrestin 2 expression and ERK1/2 activation in the DH were critical for the preventative effects of sevoflurane exposures on ischemia-induced depressive-like behaviors. Taken together, our results suggested that sevoflurane exposure after brain ischemia may prevent the development of depression, and such preventative effects of sevoflurane are likely ascribed to the activation of CB1 receptor mediated beta-arrestin 2-ERK1/2 signaling pathways. We propose that the following mechanisms are critical for the preventative effects of sevoflurane against post stroke depressive and anxiety behaviors: repeated sevoflurane exposure after transient brain ischemia enhances N-arachidonoylethanolamine (AEA) and 2 Arachidonoylglycerol (2-AG) levels and normalize cannabinoid receptor type 1 (CB1) receptor expression in the dorsal hippocampus, which results in enhanced interaction of beta-arrestin 2 and extracellular signal-regulated kinases (ERK1/2) and increased ERK1/2 activation, leading to decreased depressive and anxiety behaviors. We think these findings should provide a new strategy for treatment of post-stroke depression. PMID- 26991410 TI - Relevant risk factors for positive lateral margin after en bloc endoscopic submucosal dissection for early gastric adenocarcinoma. AB - OBJECTIVE: This study aimed to systematically assess the relevant risk factors of positive lateral margin (LM) after en bloc resection of early gastric adenocarcinoma. METHODS: A total of 242 patients who had undergone endoscopic submucosal dissection (ESD) due to early gastric lesions from January 2009 to March 2015 were included in the study. Clinicopathological features of the lesions and the risk factors related to positive LM were analyzed. RESULTS: The curative rate was 82.2% and positive LM was found in 12.4% of the lesions. Univariate analysis showed that positive LM was significantly associated with the tumor location (at the upper third of the stomach), size (>3 cm), histological findings, the presence of lymphovascular invasion and deeper invasion depth. Moreover, positive LM had a higher incidence of recurrent or residual tumors. A multivariate analysis showed that the location, tumor size and histological classification of tumors were independent risk factors for positive LM. CONCLUSIONS: Positive LM is closely related to the upper third of stomach, a tumor larger than 3 cm and a mixed-type carcinoma. Additionally, positive LM has a predilection for recurrent or residual tumors. PMID- 26991411 TI - Location, Location, Location: Differential Toxicity of Protein Aggregates in Subcellular Compartments. PMID- 26991412 TI - A model for measuring the health burden of classic congenital adrenal hyperplasia in adults. AB - AIM: Patients with classic congenital adrenal hyperplasia (CAH) have poor health outcomes. In the absence of a comprehensive observational study, this manuscript provides a model to estimate the lifetime disease burden of adults with classic CAH. METHODS: The model, built in Excel, comprises subdomains addressing the health consequences of CAH and synthesises evidence from clinical and epidemiological studies on health outcomes. RESULTS: The model estimates that adults with classic CAH will implement 'sick day rules' (doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their lifetime and attend hospital for adrenal crisis on 11 occasions. In a population of 1000, over 200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7 years of life. Patients with CAH may also suffer from excess CVD events. Treatment with glucocorticoids almost doubles the risk of bone fractures in patients with CAH compared to the general population, leading on average to an additional 0.8 fractures per patient with CAH over their lifetime. CONCLUSIONS: The disease burden model highlights gaps in evidence, particularly regarding intensity of care and adrenal crisis, and the relationship between control of CAH and risks of CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact of new clinical pathways and therapeutic interventions in terms of clinical events and cost. PMID- 26991413 TI - I2-Catalyzed Multicomponent Reactions for Accessing Densely Functionalized Pyrazolo[1,5-a]pyrimidines and Their Disulphenylated Derivatives. AB - New I2-catalyzed multicomponent bicyclization reactions of beta-ketonitriles with sulfonyl hydrazides have been established, providing a direct and metal-free access toward unreported pyrazolo[1,5-a]pyrimidin-4-ium sulfonates. The latter could be quantitatively converted into densely functionalized pyrazolo[1,5 a]pyrimidines in the presence of bases. Using sulfonyl hydrazides as a sulfenylating agent, the resulting pyrazolo[1,5-a]pyrimidines enabled I2 catalyzed unprecedented disulphenylations to access fully substituted pyrazolo[1,5-a]pyrimidines through direct C(sp(2))-H bond bifunctionalization. PMID- 26991414 TI - Impact of ribavirin dosage in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin combination therapy. AB - The factors associated with sustained virologic response (SVR) in chronic hepatitis C (CH-C) genotype 1 patients treated with simeprevir (SMV), pegylated interferon (Peg-IFN) plus ribavirin (RBV) triple therapy have not been fully investigated. Two hundred and twenty-nine treatment-naive CH-C patients treated with SMV triple therapy were enrolled in this study. The overall SVR rate was 87% in per-protocol analysis. In multivariate analysis, the interleukin (IL) 28B genotype (rs8099917, TT vs. non-TT, odds ratio [OR]: 0.044, P = 0.001) and RBV dose (< 10/10-12/ >= 12 mg/kg/day, OR: 4.513, P = 0.041) were significant factors associated with SVR. In patients with the IL28B non-TT genotype, RBV dose affected SVR dose-dependently in stratified analysis of RBV dose (P = 0.015); it was 44% (8/18) for patients administered <10 mg/kg/day of RBV, 78% (14/18) for those administered 10-12 mg/kg/day of RBV, and 100% (3/3) for those administered >=12 mg/kg/day of RBV, whereas in patients with the IL28B TT genotype, a significant correlation between SVR and RBV dose was not observed (P = 0.229). Regarding RBV dose reduction of less than 10 mg/kg/day, the inosine triphosphate pyrophosphatase (ITPA) genotype (rs1127354, CC vs. non-CC, OR: 0.239, P = 0.003) and age (by 1 y.o., OR: 1.084, P = 0.002) were significant independent factors. RBV dosage affected SVR dose-dependently in patients with the IL28B non-TT genotype treated with SMV triple therapy. Special attention to anemia progression and RBV dosage should be paid to aged patients with the ITPA CC genotype. J. Med. Virol. 88:1776-1784, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991415 TI - Active Foot Synovitis in Patients With Rheumatoid Arthritis: Unstable Remission Status, Radiographic Progression, and Worse Functional Outcomes in Patients With Foot Synovitis in Apparent Remission. AB - OBJECTIVE: To determine whether foot synovitis is associated with adverse radiographic and functional outcomes after 3 years in an inception rheumatoid arthritis (RA) cohort receiving treat-to-target combination disease-modifying antirheumatic drug therapy. METHODS: Disease activity was assessed in early RA patients (n = 266) using the Disease Activity Score in 28 joints, Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Radiographic outcomes were assessed with annual hand and feet radiographs and quality of life with the Short Form 36 (SF-36). The prevalence of remission and foot synovitis was calculated using marginal binomial generalized estimating equations, transition between remission and nonremission states by a multistate Markov model, and changes in radiographic scores by a negative binomial mixed regression log-link model. Population-matched SF-36 data were analyzed by mixed effects linear regression. RESULTS: Disease activity scores that omit foot joints were modest in their ability to capture foot synovitis. Despite the relative stringency of the SDAI and CDAI for remission, 25-36% of patients in remission had foot synovitis. In patients in remission, foot synovitis predicted transition from remission into relapse by up to 2-fold. The sustainability of remission markedly influenced the progression of erosion scores (P = 0.006). After adjusting for disease activity, foot synovitis was associated with worse SF-36 physical functioning scores (P = 0.025). CONCLUSION: Disease activity measures that omit foot joints capture foot synovitis poorly. When it is used to define remission, foot synovitis is found in a substantial proportion of patients, which predicts relapse and worse physical function. Foot synovitis influences the sustainability of remission, which in turn markedly influences radiographic progression. Regardless of remission status, persistent foot synovitis should prompt therapy escalation in order to improve long-term outcomes. PMID- 26991417 TI - Corrigendum: Translation Microscopy (TRAM) for super-resolution imaging. PMID- 26991418 TI - Adaptable texture-based segmentation by variance and intensity for automatic detection of semitranslucent and pink blush areas in basal cell carcinoma. AB - BACKGROUND: Pink blush is a common feature in basal cell carcinoma (BCC). A related feature, semitranslucency, appears as smooth pink or orange regions resembling skin color. We introduce an automatic method for detection of these features based on smoothness and brightness. We also introduce a neighborhood correction method for texture area correction. METHODS: Smoothness and brightness were analyzed over four bands: luminance, red, green, and blue, then merged using variance-based dynamic thresholding. Dermoscopic images of 100 biopsy-proven BCCs and 254 competitive benign mimics were used to train the algorithm. Sixteen color and texture features were extracted from the automatically detected areas. The confusion matrix for the algorithm showed 15 classification errors in the training set for the 354 images: three errors in the BCC set and 12 errors in the benign set. RESULTS: Logistic regression analysis on a separate 1024-image test set was able to achieve good separation of BCC from benign lesions with an area under the receiver operating characteristic curve (ROC) of 0.878 and 0.877 using manually-created and automatically-generated BCC border masks, respectively. CONCLUSION: This pilot study indicates that automatic detection of semitranslucent and pink blush areas in BCC is feasible using colors and first order texture statistics. PMID- 26991419 TI - Outcomes of stage I TTTS or liquor discordant twins: a single-centre review. AB - OBJECTIVES: To investigate rates of progression, regression and stabilisation and outcomes for stage I twin-twin transfusion syndrome (TTTS) and significant liquor discordant (LD) monochorionic diamniotic (MCDA) twins referred to the New South Wales Fetal Therapy Centre between June 2007 and May 2013. METHODS: Retrospective cohort study of 329 monochorionic referrals, of whom 47 had LD and 28 had stage I TTTS at presentation; 43 were stage I or higher at any time during surveillance. Clinical progression, rates of therapy, survival and associated complications were evaluated. RESULTS: Of stage I cases, 64% (18/28) remained stable or regressed, with 60% (6/10) of those progressing becoming at least stage II within 2 weeks. Of LD cases, 7/47 (15%) progressed to stage I TTTS, 8/47 (17%) to stage II or higher and 3/47 (6%) to selective intrauterine growth restriction (38% total). CONCLUSION: While a stable clinical picture was the most common outcome in stage I/LD presentations, progression to stage >= II TTTS occurred in 36 and 17% respectively, indicating that LD is not a benign finding. Rapid progression in the majority of progressive cases and modest overall survival rates support close surveillance of these pregnancies and investigation of laser therapy as a first-line treatment of stage I TTTS. (c) 2016 John Wiley & Sons, Ltd. PMID- 26991420 TI - Asymmetric Total Synthesis of Propindilactone G, Part 2: Enantioselective Construction of the Fully Functionalized BCDE Ring System. AB - The enantioselective synthesis of the fully functionalized BCDE tetracyclic ring system of propindilactone G (A) is reported. Several synthetic methods were developed and applied to achieve this goal, including: 1) an asymmetric Diels Alder reaction in the presence of Hayashi's catalyst for the synthesis of optically pure key intermediate 3; 2) an intramolecular Pauson-Khand reaction (PKR) for the stereoselective synthesis of the BCDE ring with an all-carbon chiral quaternary center at the C13 position by using the TMS-substituted acetylene as the substrate; and 3) Pd-catalyzed reductive hydrogenolysis for the stereoselective synthesis of the fully functionalized BCDE tetracyclic ring system. The chemistry developed herein provided a greater understanding of the total synthesis propindilactone G (A) and its analogues. PMID- 26991416 TI - Collagen-binding proteins of Streptococcus mutans and related streptococci. AB - The ability of Streptococcus mutans to interact with collagen through the expression of collagen-binding proteins (CBPs) bestows this oral pathogen with an alternative to the sucrose-dependent mechanism of colonization classically attributed to caries development. Based on the abundance and distribution of collagen throughout the human body, stringent adherence to this molecule grants S. mutans with the opportunity to establish infection at different host sites. Surface proteins, such as SpaP, WapA, Cnm and Cbm, have been shown to bind collagen in vitro, and it has been suggested that these molecules play a role in colonization of oral and extra-oral tissues. However, robust collagen binding is not achieved by all strains of S. mutans, particularly those that lack Cnm or Cbm. These observations merit careful dissection of the contribution from these different CBPs towards tissue colonization and virulence. In this review, we will discuss the current understanding of mechanisms used by S. mutans and related streptococci to colonize collagenous tissues, and the possible contribution of CBPs to infections in different sites of the host. PMID- 26991421 TI - Titanium Salan/Salalen Complexes: The Twofaced Janus of Asymmetric Oxidation Catalysis. AB - Optically pure chiral epoxides and sulfoxides are ubiquitous building blocks in fine organic synthesis, employed in the pharmaceutical, agrochemical, and cosmetic industries. On the road to chiral epoxides and sulfoxides, efficient and stereoselective transition metal-based catalysts are the most promising guides. Among transition metals, we favor titanium for its cheapness and availability, nontoxicity, and well-known ability to catalyze a variety of stereoselective transformations, including oxidations with environmentally benign H2O2. In this personal account, we summarize the state-of-the-art of rational design of chiral titanium(IV) salan and salalen catalysts, and investigations of their catalytic reactivities and stereoselectivities in the epoxidations of olefins and oxidations of thioethers, unraveling the peculiarities and mechanisms of their catalytic action. PMID- 26991422 TI - Androgen receptor-related diseases: what do we know? AB - The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen-AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post-transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post-transcriptional stages. PMID- 26991423 TI - Porcine Pluripotent Stem Cells Derived from IVF Embryos Contribute to Chimeric Development In Vivo. AB - Although the pig is considered an important model of human disease and an ideal animal for the preclinical testing of cell transplantation, the utility of this model has been hampered by a lack of genuine porcine embryonic stem cells. Here, we derived a porcine pluripotent stem cell (pPSC) line from day 5.5 blastocysts in a newly developed culture system based on MXV medium and a 5% oxygen atmosphere. The pPSCs had been passaged more than 75 times over two years, and the morphology of the colony was similar to that of human embryonic stem cells. Characterization and assessment showed that the pPSCs were alkaline phosphatase (AKP) positive, possessed normal karyotypes and expressed classic pluripotent markers, including OCT4, SOX2 and NANOG. In vitro differentiation through embryonic body formation and in vivo differentiation via teratoma formation in nude mice demonstrated that the pPSCs could differentiate into cells of the three germ layers. The pPSCs transfected with fuw-DsRed (pPSC-FDs) could be passaged with a stable expression of both DsRed and pluripotent markers. Notably, when pPSC-FDs were used as donor cells for somatic nuclear transfer, 11.52% of the reconstructed embryos developed into blastocysts, which was not significantly different from that of the reconstructed embryos derived from porcine embryonic fibroblasts. When pPSC-FDs were injected into day 4.5 blastocysts, they became involved in the in vitro embryonic development and contributed to the viscera of foetuses at day 50 of pregnancy as well as the developed placenta after the chimeric blastocysts were transferred into recipients. These findings indicated that the pPSCs were porcine pluripotent cells; that this would be a useful cell line for porcine genetic engineering and a valuable cell line for clarifying the molecular mechanism of pluripotency regulation in pigs. PMID- 26991424 TI - Establishment and characterization of a canine soft tissue sarcoma patient derived xenograft model. AB - Spontaneously occurring soft tissue sarcoma (STS) is relatively common in canine cancer patients. Because of the similarities to human disease, canine STSs are a valuable and readily available resource for the study of new therapeutics. In this study, a canine patient-derived xenograft (PDX) model, CDX-STS2, was established. The CDX-STS2 model was engrafted and expanded for systemic administration studies with chemotherapeutic agents commonly used to treat STS, including doxorubicin, docetaxel and gemcitabine. Immunohistochemistry for drug specific biomarkers and tumour growth measurement revealed tumour sensitivity to doxorubicin and docetaxel, whereas gemcitabine had no effect on tumour growth. Although many human PDX tumour models have been established, relatively few canine PDX models have been reported to date. CDX-STS2 represents a new STS PDX research model of canine origin that will be useful in bridging preclinical research with clinical studies of STS in pet dogs. PMID- 26991426 TI - Reactivity Study of a Pyridyl-1-azaallylgermanium(I) Dimer: Synthesis of Heavier Ether and Ester Analogues of Germanium. AB - The reactivity study of a pyridyl-1-azaallylgermanium(I) dimer LGe-GeL [1; L = N(SiMe3)C(Ph)C(SiMe3)(C5H4N-2)] with different stoichiometric ratios of elemental selenium and tellurium is described. The reactions of 1 with 1 equiv of selenium and tellurium afforded the first examples of heavier ether analogues of germanium, bis(germylene) selenide and telluride LGe(MU-E)GeL [E = Se (2) and Te (3)], respectively. Meanwhile, the reactions of 1 with 2 equiv of selenium and tellurium gave the heavier ester analogues LGe?E(MU-E)GeL [E = Se (4) and (5)]. All compounds have been characterized by X-ray crystallography and multinuclear NMR spectroscopy. PMID- 26991425 TI - Promotion of Expansion and Differentiation of Hematopoietic Stem Cells by Interleukin-27 into Myeloid Progenitors to Control Infection in Emergency Myelopoiesis. AB - Emergency myelopoiesis is inflammation-induced hematopoiesis to replenish myeloid cells in the periphery, which is critical to control the infection with pathogens. Previously, pro-inflammatory cytokines such as interferon (IFN)-alpha and IFN-gamma were demonstrated to play a critical role in the expansion of hematopoietic stem cells (HSCs) and myeloid progenitors, leading to production of mature myeloid cells, although their inhibitory effects on hematopoiesis were also reported. Therefore, the molecular mechanism of emergency myelopoiesis during infection remains incompletely understood. Here, we clarify that one of the interleukin (IL)-6/IL-12 family cytokines, IL-27, plays an important role in the emergency myelopoiesis. Among various types of hematopoietic cells in bone marrow, IL-27 predominantly and continuously promoted the expansion of only Lineage-Sca-1+c-Kit+ (LSK) cells, especially long-term repopulating HSCs and myeloid-restricted progenitor cells with long-term repopulating activity, and the differentiation into myeloid progenitors in synergy with stem cell factor. These progenitors expressed myeloid transcription factors such as Spi1, Gfi1, and Cebpa/b through activation of signal transducer and activator of transcription 1 and 3, and had enhanced potential to differentiate into migratory dendritic cells (DCs), neutrophils, and mast cells, and less so into macrophages, and basophils, but not into plasmacytoid DCs, conventional DCs, T cells, and B cells. Among various cytokines, IL-27 in synergy with the stem cell factor had the strongest ability to augment the expansion of LSK cells and their differentiation into myeloid progenitors retaining the LSK phenotype over a long period of time. The experiments using mice deficient for one of IL-27 receptor subunits, WSX-1, and IFN-gamma revealed that the blood stage of malaria infection enhanced IL-27 expression through IFN-gamma production, and the IL-27 then promoted the expansion of LSK cells, differentiating and mobilizing them into spleen, resulting in enhanced production of neutrophils to control the infection. Thus, IL-27 is one of the limited unique cytokines directly acting on HSCs to promote differentiation into myeloid progenitors during emergency myelopoiesis. PMID- 26991427 TI - Habitual instigation and habitual execution: Definition, measurement, and effects on behaviour frequency. AB - OBJECTIVES: 'Habit' is a process whereby situational cues generate behaviour automatically, via activation of learned cue-behaviour associations. This article presents a conceptual and empirical rationale for distinguishing between two manifestations of habit in health behaviour, triggering selection and initiation of an action ('habitual instigation'), or automating progression through subactions required to complete action ('habitual execution'). We propose that habitual instigation accounts for habit-action relationships, and is the manifestation captured by the Self-Report Habit Index (SRHI), the dominant measure in health psychology. DESIGN: Conceptual analysis and prospective survey. METHODS: Student participants (N = 229) completed measures of intentions, the original, non-specific SRHI, an instigation-specific SRHI variant, an execution specific variant, and, 1 week later, behaviour, in three health domains (flossing, snacking, and breakfast consumption). Effects of habitual instigation and execution on behaviour were modelled using regression analyses, with simple slope analysis to test habit-intention interactions. Relationships between instigation, execution, and non-specific SRHI variants were assessed via correlations and factor analyses. RESULTS: The instigation-SRHI was uniformly more predictive of behaviour frequency than the execution-SRHI and corresponded more closely with the original SRHI in correlation and factor analyses. CONCLUSIONS: Further, experimental work is needed to separate the impact of the two habit manifestations more rigorously. Nonetheless, findings qualify calls for habit-based interventions by suggesting that behaviour maintenance may be better served by habitual instigation and that disrupting habitual behaviour may depend on overriding habits of instigation. Greater precision of measurement may help to minimize confusion between habitual instigation and execution. Statement of contribution What is already known on this subject? Habit is often used to understand, explain, and change health behaviour. Making behaviour habitual has been proposed as a means of maintaining behaviour change. Concerns have been raised about the extent to which health behaviour can be habitual. What does this study add? A conceptual and empirical rationale for discerning habitually instigated and habitually executed behaviour. Results show habit-behaviour effects are mostly attributable to habitual instigation, not execution. The most common habit measure, the Self-Report Habit Index, measures habitual instigation, not execution. PMID- 26991428 TI - Successful treatment of thyroidectomy scar with a pneumatic needleless injector and silicone gel. PMID- 26991429 TI - Quality of Life Analysis and Smoking Correlation in Symptomatic Spine Osteoarthritis: A Nationwide Health Survey Analysis of an Elderly Population with EQ-5D. AB - OBJECTIVES: To analyze quality of life in people with symptomatic spine osteoarthritis (OA) using the results of a cross-sectional, nationwide survey. MATERIALS AND METHODS: This study used data from the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V-5; 2010-2012). After excluding ineligible subjects, the total number of subjects in the study was 8,963, including 4,091 males and 4,872 females. All participants reported disabilities related to spine OA. Plain radiographs of the spine were taken for all participants. RESULTS: Age, sex, smoking, drinking, education, and income level were significantly related to spine OA morbidity (P<0.05). OA morbidity was significantly higher in female ex-smokers (OR; 2.94, P<0.05). Quality of life (EQ 5D: L1~5) was significantly compromised in the group with spine OA compared to the group without spine OA (P<0.05). Overall, LQ 1, 2, 3, 4, and 5 domain scores were significantly higher in the group with spine OA (P<0.05). In the group with spine OA, quality of life was reduced on more than three questions for 34.3% of the group (EQ-5D: grade>=2); on two questions, for 18.5% of the group; and on one question, for 11.1% of the group. Mental stress, melancholy, and suicidal thinking were also more common in the group with spine OA (P<0.05). The group with radiographic spine OA but without symptoms did not have compromised EQ-5D scores, whereas the group with radiographic OA and symptoms showed a significantly reduced quality of life. CONCLUSIONS: Quality of life was significantly reduced in the group with symptomatic spine OA in a large cross sectional analysis. Physicians should consider quality of life in the treatment of patients with spine OA. PMID- 26991430 TI - Daily Home Hemodialysis Is an Available Option for Renal Replacement Therapy in Spain. AB - The objective of the present study was to analyze the characteristics and survival of patients from our hospital who started home hemodialysis. We analyzed all patients receiving home hemodialysis from 1969 to 2015 (51 patients; age 45 +/- 23 years; men 77%). We collected characteristics, hospital admission, and mortality. After a median follow-up of 43 (22-76) months, we found 0-1 hospital admissions per year. Sixty-nine percent received a kidney transplant, and the global mortality was 10%. Survival at 5 years was 96%. Mean equivalent renal urea clearance was 15.6 +/- 4.2 mL/min, the beta-2 microglobulin reduction rate was 67 +/- 18%, the number of antihypertension drugs was 0.7 +/- 0.3, and the erythropoietin resistance index was 3.7 +/- 2.1 IU/kg/week/g/dL. Daily home hemodialysis is a viable option for renal replacement therapy and should be offered alongside other therapies. PMID- 26991431 TI - Joining forces: first application of a rapamycin-induced dimerizable Cre system for conditional null mutant analysis in Leishmania. AB - Reverse genetics in Leishmania spp has gained importance beyond basic research as efforts increase to discover and validate new drug targets. Often, the most promising targets are essential for viability of the parasites, defying a genetic analysis by current gene replacement strategies. Duncan et al. demonstrate the applicability of DiCre recombination in Leishmania for induced replacement of the kinase CRK3 gene in promastigotes. DiCre gene replacement leads to the rapid loss of the gene and allows monitoring the phenotypic effects of the loss of function, eliminating the need for prolonged cultivation and selection. Implementation of the DiCre approach will allow functional genetics of the most important of Leishmania genes and is likely to boost genetic research and drug target discovery. PMID- 26991433 TI - Ca-Dependent Folding of Human Calumenin. AB - Human calumenin (hCALU) is a six EF-hand protein belonging to the CREC family. As other members of the family, it is localized in the secretory pathway and regulates the activity of SERCA2a and of the ryanodine receptor in the endoplasmic reticulum (ER). We have studied the effects of Ca2+ binding to the protein and found it to attain a more compact structure upon ion binding. Circular Dichroism (CD) measurements suggest a major rearrangement of the protein secondary structure, which reversibly switches from disordered at low Ca2+ concentrations to predominantly alpha-helical when Ca2+ is added. SAXS experiments confirm the transition from an unfolded to a compact structure, which matches the structural prediction of a trilobal fold. Overall our experiments suggest that calumenin is a Ca2+ sensor, which folds into a compact structure, capable of interacting with its molecular partners, when Ca2+ concentration within the ER reaches the millimolar range. PMID- 26991434 TI - Association between EEG modulation, psychotic-like experiences and cognitive performance in the general population. AB - AIM: An association between deficit of electroencephalographic (EEG) modulation during an odd-ball task and psychotic symptoms has been described in clinical samples, in agreement with the proposed role for altered salience in psychosis. To discard the possible influence of medication, the relationship between psychotic-like experiences and EEG modulation in the general population was explored. METHODS: EEG and psychotic-like experiences were assessed in 194 healthy subjects during a P300 paradigm. EEG modulation was assessed as changes from pre-stimulus to response windows in spectral entropy (SE, a measurement of signal irregularity), median frequency (MF, a quantifier of the frequency distribution of oscillatory activity) and theta, alpha, beta-1, beta-2 and gamma relative power (RP, a summary of the distribution of spectral components). RESULTS: A significant widespread decrease in SE and MF from baseline to response was found, with a significant increase in RP for theta and a decrease for higher frequency bands, supporting an increase in EEG regularity and a slowing of brain oscillations during the response. Furthermore, a significant association was found between SE modulation and distress of negative psychotic-like experiences, as well as between verbal memory and RP modulation for beta-1. Performance in verbal fluency was associated with the increase in theta RP during the response. CONCLUSION: EEG irregularity of healthy subjects decreased at the expense of a larger contribution of theta RP and a decreased contribution of fast frequency bands. Subjects with smaller modulation showed poorer cognitive scores and greater distress of negative psychotic-like experiences. PMID- 26991432 TI - The lipid interaction capacity of Sin a 2 and Ara h 1, major mustard and peanut allergens of the cupin superfamily, endorses allergenicity. AB - BACKGROUND: Sin a 2 (11S globulin) and Ara h 1 (7S globulin) are major allergens from yellow mustard seeds and peanut, respectively. The ability of these two allergens to interact with lipid components remains unknown. OBJECTIVE: To study the capacity of Sin a 2 and Ara h 1 to interact with lipid components and the potential effects of such interaction in their allergenic capacity. METHODS: Spectroscopic and SDS-PAGE binding assays of Sin a 2 and Ara h 1 with different phospholipid vesicles and gastrointestinal and endolysosomal digestions in the presence or absence of lipids were performed. The capacity of human monocyte derived dendritic cells (hmoDCs) to capture food allergens in the presence or absence of lipids, the induced cytokine signature, and the effect of allergens and lipids to regulate TLR2-L-induced NF-kB/AP-1 activation in THP1 cells were analyzed. RESULTS: Sin a 2 and Ara h 1 bind phosphatidylglycerol (PG) acid but not phosphatidylcholine (PC) vesicles in a pH-dependent manner. The interaction of these two allergens with lipid components confers resistance to gastrointestinal digestion, reduces their uptake by hmoDCs, and enhances their stability to microsomal degradation. Mustard and peanut lipids favor a proinflammatory environment by increasing the IL-4/IL-10 ratio and IL-1beta production by hmoDCs. The presence of mustard lipids and PG vesicles inhibits TLR2-L-induced NF-kB/AP-1 activation in THP1 cells. CONCLUSION: Sin a 2 and Ara h 1 interact with lipid components, which might well contribute to explain the potent allergenic capacity of these two clinically relevant allergens belonging to the cupin superfamily. PMID- 26991436 TI - Patients' experience with intermittent catheterisation in everyday life. AB - AIMS AND OBJECTIVES: This study reports about the experiences of 11 patients in the Netherlands who use intermittent self-catheterisation to manage their symptoms. The aim of the study was to get insight in underlying barriers and facilitators for patients dealing with intermittent catheterisation in everyday life. BACKGROUND: Studies show that intermittent catheterisation has an impact on everyday life. A positive effect does not guarantee that patients maintain catheterisation over a longer period of time. After the implementation of a guideline, a quantitative study was performed to determine successful intermittent catheterisation. The patients of this study had previously taken part in this quantitative study. DESIGN: This is a qualitative multicentre study using semistructured in-depth interviews with 11 patients between March-May 2013. METHODS: Inclusion criteria included patients of a quantitative study (n = 124) with a variety of diagnoses referred to the outpatient clinic. Those who received instruction from the researcher and who at start of the study performed catheterisation <=3 months were excluded. Of the total number that met the inclusion criteria, every fourth patient was invited to participate in an interview. Patients were asked about the introducing of intermittent catheterisation, the incorporation into everyday life, the progress after the instruction and guidance perceived, the cause of the bladder problem and the motivation to start intermittent catheterisation. RESULTS: Eleven interviews were performed (six males/five females). All patients described the instruction and follow-up care as positive. Barriers were the preparation before the handling, which is more difficult than the catheterisation itself, and the fact that patients felt constrained by the need to plan convenient times to catheterise themselves. CONCLUSION: This study shows that patients who perform catheterisation are satisfied about the instruction and follow-up care. Important barriers in everyday life are the preparation and the need to plan convenient times. RELEVANCE TO CLINICAL PRACTICE: Interviewing patients gave important additional information about dealing with intermittent catheterisation in everyday life. Prescribers and teachers of intermittent catheterisation must realise that they often have to high expectations of patients when it comes to being flexible in frequency of catheterisation. It is important to realise that patients experience barriers of which healthcare workers are not always aware of, such as the preparation before the handling and feeling constrained by the need to plan convenient times to catheterise. The outcome of this study can be used to improve the content of patient information brochures and guidelines for intermittent catheterisation. PMID- 26991435 TI - Recovery of full donor chimerism with ibrutinib therapy in relapsed CLL after allogeneic stem cell transplantation. PMID- 26991437 TI - A study of radiogallium aqueous chemistry: in vitro and in vivo characterisation of (67) Ga-hydrolysed-stannous fluoride particles. AB - The objective of this study was to explore the aqueous chemistry of gallium using (67) Ga-chloride starting material, by radiolabelling hydrolysed(h)-stannous fluoride particles and then characterising the optimal formulation for radiochemical purity (RCP) and radioactive particle size distribution in vitro. The pilot reactions determined stannous fluoride was added to (67) Ga-acetate under nitrogen and then heated at 100 degrees C for 20 min to achieve >=95% RCP and (67) Ga-particles were >3 um in diameter. A high radioactive concentration of (67) Ga-h-SnF2 particles could be prepared similarly in >=97% RCP with 74% as 3-5 um and 26% >5 um in diameter. The latter formulation had larger particles than (99m) Tc-h-SnF2 colloid (96% of 1-3 um), and it resulted in a rat biodistribution of 41% in the lungs, 41% in the liver plus spleen and 18% in the carcass at 20 min after injection. The carcass activity was attributed to bone marrow and some (67) Ga-transferrin formed in blood. Isolated mixed human leucocytes were radiolabelled with (67) Ga-h-SnF2 particles in 100% efficiency, and the (67) Ga cells did not release soluble (67) Ga(3+) at room temperature over 3 h. The (67) Ga-h-SnF2 particle formulation could find a use in labelling leucocyte cells for in vivo homing studies when delayed animal imaging is required. PMID- 26991438 TI - Language at Three Timescales: The Role of Real-Time Processes in Language Development and Evolution. AB - Evolutionary developmental systems (evo-devo) theory stresses that selection pressures operate on entire developmental systems rather than just genes. This study extends this approach to language evolution, arguing that selection pressure may operate on two quasi-independent timescales. First, children clearly must acquire language successfully (as acknowledged in traditional evo-devo accounts) and evolution must equip them with the tools to do so. Second, while this is developing, they must also communicate with others in the moment using partially developed knowledge. These pressures may require different solutions, and their combination may underlie the evolution of complex mechanisms for language development and processing. I present two case studies to illustrate how the demands of both real-time communication and language acquisition may be subtly different (and interact). The first case study examines infant-directed speech (IDS). A recent view is that IDS underwent cultural to statistical learning mechanisms that infants use to acquire the speech categories of their language. However, recent data suggest is it may not have evolved to enhance development, but rather to serve a more real-time communicative function. The second case study examines the argument for seemingly specialized mechanisms for learning word meanings (e.g., fast-mapping). Both behavioral and computational work suggest that learning may be much slower and served by general-purpose mechanisms like associative learning. Fast-mapping, then, may be a real-time process meant to serve immediate communication, not learning, by augmenting incomplete vocabulary knowledge with constraints from the current context. Together, these studies suggest that evolutionary accounts consider selection pressure arising from both real-time communicative demands and from the need for accurate language development. PMID- 26991439 TI - INVOLVEMENT OF PEPTIDOGLYCAN RECOGNITION PROTEIN L6 IN ACTIVATION OF IMMUNE DEFICIENCY PATHWAY IN THE IMMUNE RESPONSIVE SILKWORM CELLS. AB - The immune deficiency (Imd) signaling pathway is activated by Gram-negative bacteria for producing antimicrobial peptides (AMPs). In Drosophila melanogaster, the activation of this pathway is initiated by the recognition of Gram-negative bacteria by peptidoglycan (PGN) recognition proteins (PGRPs), PGRP-LC and PGRP LE. In this study, we found that the Imd pathway is involved in enhancing the promoter activity of AMP gene in response to Gram-negative bacteria or diaminopimelic (DAP) type PGNs derived from Gram-negative bacteria in an immune responsive silkworm cell line, Bm-NIAS-aff3. Using gene knockdown experiments, we further demonstrated that silkworm PGRP L6 (BmPGRP-L6) is involved in the activation of E. coli or E. coli-PGN mediated AMP promoter activation. Domain analysis revealed that BmPGRP-L6 contained a conserved PGRP domain, transmembrane domain, and RIP homotypic interaction motif like motif but lacked signal peptide sequences. BmPGRP-L6 overexpression enhances AMP promoter activity through the Imd pathway. BmPGRP-L6 binds to DAP-type PGNs, although it also binds to lysine type PGNs that activate another immune signal pathway, the Toll pathway in Drosophila. These results indicate that BmPGRP-L6 is a key PGRP for activating the Imd pathway in immune responsive silkworm cells. PMID- 26991440 TI - Spinocerebellar Ataxia Type 3 in Italy: Time to Change Mind. PMID- 26991441 TI - A stress-associated NAC transcription factor (SlNAC35) from tomato plays a positive role in biotic and abiotic stresses. AB - The NAC transcription factor family participates in responses to various kinds of environmental stimuli in plants. Responses of NAC genes to abiotic stresses have been widely studied, but their functions in response to biotic stress are little reported in plants, especially in crops. In the present study, we examined the functions of a novel tomato (Solanum lycopersicum) NAC protein (SlNAC35) in abiotic and biotic stress resistance by using transgenic tobacco. Expression analysis found that SlNAC35 expression was induced by drought stress, salt stress, bacterial pathogen, and signaling molecules, suggesting its involvement in plant responses to biotic and abiotic stimuli. Moreover, transgenic lines exhibited a greater number of lateral roots and longer root length compared with Vec lines (empty vector lines) after drought and salt treatment. These results indicate that overexpression of SlNAC35 promoted root growth and development under drought and salt stresses. Higher expressions of NtARF1, NtARF2 and NtARF8 were observed under drought and salt stresses in transgenic lines, suggesting that overexpression of SlNAC35 promoted growth and development of roots in transgenic lines possibly by involving auxin signaling and by regulating NtARF expression. In addition, SlNAC35 overexpression improved resistance to bacterial pathogen in transgenic tobacco, and reactive oxygen species may be in the upstream of salicylic acid (SA) signaling in transgenic tobacco during defense response. PMID- 26991442 TI - Identifying Topics in Microblogs Using Wikipedia. AB - Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail. PMID- 26991443 TI - Lipiodol transarterial chemoembolization for hepatocellular carcinoma: Where are we now? PMID- 26991444 TI - Superficial Thrombophlebitis of the Breast in a Patient with an Arteriovenous Fistula for Hemodialysis. PMID- 26991445 TI - Toward quantification of the impact of 21st-century deforestation on the extinction risk of terrestrial vertebrates. AB - Conservation actions need to be prioritized, often taking into account species' extinction risk. The International Union for Conservation of Nature (IUCN) Red List provides an accepted, objective framework for the assessment of extinction risk. Assessments based on data collected in the field are the best option, but the field data to base these on are often limited. Information collected through remote sensing can be used in place of field data to inform assessments. Forests are perhaps the best-studied land-cover type for use of remote-sensing data. Using an open-access 30-m resolution map of tree cover and its change between 2000 and 2012, we assessed the extent of forest cover and loss within the distributions of 11,186 forest-dependent amphibians, birds, and mammals worldwide. For 16 species, forest loss resulted in an elevated extinction risk under red-list criterion A, owing to inferred rapid population declines. This number increased to 23 when data-deficient species (i.e., those with insufficient information for evaluation) were included. Under red-list criterion B2, 484 species (855 when data-deficient species were included) were considered at elevated extinction risk, owing to restricted areas of occupancy resulting from little forest cover remaining within their ranges. The proportion of species of conservation concern would increase by 32.8% for amphibians, 15.1% for birds, and 24.7% for mammals if our suggested uplistings are accepted. Central America, the Northern Andes, Madagascar, the Eastern Arc forests in Africa, and the islands of Southeast Asia are hotspots for these species. Our results illustrate the utility of satellite imagery for global extinction-risk assessment and measurement of progress toward international environmental agreement targets. PMID- 26991446 TI - Structural and Biochemical Characterization of an Octameric Carbohydrate Acetylesterase from Sinorhizobium meliloti. AB - Carbohydrate acetylesterases, which have a highly specific role among plant interacting bacterial species, remove the acetyl groups from plant carbohydrates. Here, we determined the crystal structure of Est24, an octameric carbohydrate acetylesterase from Sinorhizobium meliloti, at 1.45 A resolution and investigated its biochemical properties. The structure of Est24 consisted of five parallel beta strands flanked by alpha helices, which formed an octameric assembly with two distinct interfaces. The deacetylation activity of Est24 and its mutants around the substrate-binding pocket was investigated using several substrates, including glucose pentaacetate and acetyl alginate. Elucidation of the structure function relationships of Est24 could provide valuable opportunities for biotechnological explorations. PMID- 26991447 TI - Neuroprotective Effects of Endurance Exercise Against High-Fat Diet-Induced Hippocampal Neuroinflammation. AB - Obesity contributes to systemic inflammation, which is associated with the varied pathogenesis of neurodegenerative diseases. Growing evidence has demonstrated that endurance exercise (EE) mitigates obesity-induced brain inflammation. However, exercise-mediated anti-inflammatory mechanisms remain largely unknown. We investigated how treadmill exercise (TE) reverses obesity-induced brain inflammation, mainly focusing on toll-like receptor-4 (TLR-4)-dependent neuroinflammation in the obese rat brain after 20 weeks of a high-fat diet (HFD). TE in HFD-fed rats resulted in a significant lowering in the homeostasis model assessment of insulin resistance index, the area under the curve for glucose and abdominal visceral fat, and also improved working memory ability in a passive avoidance task relative to sedentary behaviour in HFD-fed rats, with the exception of body weight. More importantly, TE revoked the increase in HFD induced proinflammatory cytokines (tumour necrosis factor alpha and interleukin 1beta) and cyclooxygenase-2, which is in parallel with a reduction in TLR-4 and its downstream proteins, myeloid differentiation 88 and tumour necrosis factor receptor associated factor 6, and phosphorylation of transforming growth factor beta-activated kinase 1, IkBalpha and nuclear factor-kappaB. Moreover, TE reduced an indicator of microglia activation, ionised calcium-binding adapter molecule-1, and also decreased glial fibrillary acidic protein, an indicator of gliosis formed by activated astrocytes in the cerebral cortex and the hippocampal dentate gyrus, compared to HFD-fed sedentary rats. Finally, EE up-regulated the expression of anti-apoptotic protein, Bcl-2, and suppressed the expression of pro apoptotic protein, Bax, in the hippocampus compared to HFD-fed sedentary rats. Taken together, these data suggest that TE may exert neuroprotective effects as a result of mitigating the production of proinflammatory cytokines by inhibiting the TLR4 signalling pathways. The results of the present study suggest that the unique combination of the beneficial effects of TE on the restoration of the blood profile and the anti-inflammatory and anti-apoptotic effects on cognitive function should inspire further investigations into its therapeutic potential for metabolic disorders and neurodegenerative diseases. PMID- 26991448 TI - A model-based approach to sample size estimation in recent onset type 1 diabetes. AB - BACKGROUND: The area under the curve C-peptide following a 2-h mixed meal tolerance test from 498 individuals enrolled on five prior TrialNet studies of recent onset type 1 diabetes from baseline to 12 months after enrolment were modelled to produce estimates of its rate of loss and variance. RESULTS: Age at diagnosis and baseline C-peptide were found to be significant predictors, and adjusting for these in an ANCOVA resulted in estimates with lower variance. CONCLUSIONS: Using these results as planning parameters for new studies results in a nearly 50% reduction in the target sample size. The modelling also produces an expected C-peptide that can be used in observed versus expected calculations to estimate the presumption of benefit in ongoing trials. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991449 TI - Actein protects against methylglyoxal-induced oxidative damage in osteoblastic MC3T3-E1 cells. AB - BACKGROUND: Methylglyoxal (MG) is an endogenous product of glucose metabolism known to be toxic to cells and to be present in elevated concentrations under certain pathophysiological conditions. In the present study the effect of actein isolated from black cohosh on MG-induced cytotoxicity was investigated in MC3T3 E1 osteoblastic cells. RESULTS: Treatment of MC3T3-E1 osteoblastic cells with actein prevented MG-induced cell death and the production of intracellular reactive oxygen species (ROS), mitochondrial superoxide, inflammatory cytokines and soluble receptor for advanced glycation end-products (sRAGE). In addition, actein increased the activity of glyoxalase I and levels of reduced glutathione (GSH) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). These findings suggest that actein protects against MG-induced cell damage by reducing oxidative stress and increasing MG detoxification. Treatment with actein prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation and adenosine triphosphate (ATP) loss. Additionally, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha), nuclear respiratory factor 1 (NRF-1) and nitric oxide (NO) levels were significantly increased by actein, suggesting that actein may induce mitochondrial biogenesis. CONCLUSION: This study demonstrates that actein reduces MG-induced damage in osteoblastic MC3T3-E1 cells by enhancing antioxidant defenses, the glyoxalase system and mitochondrial biogenesis. (c) 2016 Society of Chemical Industry. PMID- 26991450 TI - Ligand-Promoted C(sp(3) )-H Olefination en Route to Multi-functionalized Pyrazoles. AB - A Pd-catalyzed/N-heterocycle-directed C(sp(3) )-H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd catalyzed C(sp(3) )-H olefination for the first time. Cu(OAc)2 instead of Ag(+) salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles. PMID- 26991452 TI - Magnetic resonance imaging of perianal Crohn's disease. PMID- 26991451 TI - A Mixed-Ligand Chiral Rhodium(II) Catalyst Enables the Enantioselective Total Synthesis of Piperarborenine B. AB - A novel, mixed-ligand chiral rhodium(II) catalyst, Rh2(S-NTTL)3(dCPA), has enabled the first enantioselective total synthesis of the natural product piperarborenine B. A crystal structure of Rh2(S-NTTL)3(dCPA) reveals a "chiral crown" conformation with a bulky dicyclohexylphenyl acetate ligand and three N naphthalimido groups oriented on the same face of the catalyst. The natural product was prepared on large scale using rhodium-catalyzed bicyclobutanation/ copper-catalyzed homoconjugate addition chemistry in the key step. The route proceeds in ten steps with an 8% overall yield and 92% ee. PMID- 26991454 TI - Editorial: In defence of patients. PMID- 26991453 TI - A Protein Complex Map of Trypanosoma brucei. AB - The functions of the majority of trypanosomatid-specific proteins are unknown, hindering our understanding of the biology and pathogenesis of Trypanosomatida. While protein-protein interactions are highly informative about protein function, a global map of protein interactions and complexes is still lacking for these important human parasites. Here, benefiting from in-depth biochemical fractionation, we systematically interrogated the co-complex interactions of more than 3354 protein groups in procyclic life stage of Trypanosoma brucei, the protozoan parasite responsible for human African trypanosomiasis. Using a rigorous methodology, our analysis led to identification of 128 high-confidence complexes encompassing 716 protein groups, including 635 protein groups that lacked experimental annotation. These complexes correlate well with known pathways as well as for proteins co-expressed across the T. brucei life cycle, and provide potential functions for a large number of previously uncharacterized proteins. We validated the functions of several novel proteins associated with the RNA-editing machinery, identifying a candidate potentially involved in the mitochondrial post-transcriptional regulation of T. brucei. Our data provide an unprecedented view of the protein complex map of T. brucei, and serve as a reliable resource for further characterization of trypanosomatid proteins. The presented results in this study are available at: www.TrypsNetDB.org. PMID- 26991455 TI - Defining 'nutraceuticals': neither nutritious nor pharmaceutical. AB - There are widespread inconsistencies and contradictions in the many published definitions of 'nutraceuticals' and 'functional foods', demonstrating wholesale uncertainty about what they actually are. Furthermore, in a 2014 lecture, the inventor of the term 'nutraceutical', confessing that nutraceuticals do not work, said that 'the quest to demonstrate whether ... long-term supplementation [with nutraceuticals] can prevent serious diseases ... has come to an end'. Definitions of 'nutraceuticals' and related terms, still widely used, should therefore be explored systematically. There are no internationally agreed definitions of 'nutraceuticals' and 'functional foods', or of similar terms, such as 'health foods', or of terms related to herbal products, which are sometimes referred to as 'nutraceuticals', compounding the confusion. 'Nutraceuticals' and 'functional foods' are vague, nondiscriminatory, unhelpful terms; the evidence suggests that they should be abandoned in favour of more precise terms. The term 'dietary supplement' is widely used to designate formulations that are also called 'nutraceuticals' but it would be better restricted to individual compounds used to treat or prevent deficiencies. 'Fortified foods', sometimes called 'designer foods', are foods to which compounds of proven therapeutic or preventive efficacy (e.g. folic acid) have been added. Other terms, such as 'food', 'foodstuffs', 'eat', 'drink', and 'nutrition', are well defined, as are 'medicinal products' and 'pharmaceutical formulations'. Dietary regimens, such as Mediterranean or nitrate-rich diets or vegetarianism, can affect health. A dietary regimen of this kind can be defined as a programme of food, of a defined kind and/or quantity, prescribed or adopted for the restoration or preservation of health. PMID- 26991456 TI - Does Speaking Two Dialects in Daily Life Affect Executive Functions? An Event Related Potential Study. AB - Whether using two languages enhances executive functions is a matter of debate. Here, we take a novel perspective to examine the bilingual advantage hypothesis by comparing bi-dialect with mono-dialect speakers' performance on a non linguistic task that requires executive control. Two groups of native Chinese speakers, one speaking only the standard Chinese Mandarin and the other also speaking the Southern-Min dialect, which differs from the standard Chinese Mandarin primarily in phonology, performed a classic Flanker task. Behavioural results showed no difference between the two groups, but event-related potentials recorded simultaneously revealed a number of differences, including an earlier P2 effect in the bi-dialect as compared to the mono-dialect group, suggesting that the two groups engage different underlying neural processes. Despite differences in the early ERP component, no between-group differences in the magnitude of the Flanker effects, which is an index of conflict resolution, were observed in the N2 component. Therefore, these findings suggest that speaking two dialects of one language does not enhance executive functions. Implications of the current findings for the bilingual advantage hypothesis are discussed. PMID- 26991457 TI - Comparison of small animal CT contrast agents. AB - Non-invasive in vivo small animal computed tomography (CT) imaging provides high resolution bone scans but cannot differentiate between soft tissues. For most applications injections of contrast agents (CAs) are necessary. Aim of this study was to uncover the advantages and disadvantages of commercially available CT CAs (ExiTron nano 12 000 and 6000, eXIA 160 and 160XL, Fenestra VC and LC) regarding their pharmacokinetics, toxicological side-effects and the influence of anesthesia on the biodistribution, based on an injection volume of 100 MUL/25 g body weight. The pharmacokinetics of the CAs were determined for up to five days. The CA-induced toxicological/physiological side-effects were evaluated by determining blood counts, liver enzymes, thyroxine and total protein values, pro inflammatory mediators (messenger ribonucleic acid (mRNA)), histology and immunohistochemistry. ExiTron nano 12 000 and 6000 yielded a long-term contrast enhancement (CE) in the liver and spleen for up to five days. Some of the evaluated CAs did not show any CE at all. Anesthesia did not impair the CAs' biodistribution. The CAs differentially affected the body weight, blood counts, liver enzymes, thyroxine and total protein values. ExiTron nano 12 000 and 6000 induced histiocytes in the liver and spleen. Moreover, ExiTron nano 12 000 and eXIA 160 enhanced tumor necrosis factor (TNF) mRNA expression levels in the kidneys. Thus, we recommend ExiTron nano 12 000 and 6000 when multiple injections should be avoided. We recommend careful selection of the employed CA in order to achieve an acceptable CE in the organs of interest and to avoid influences on the animal physiology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991458 TI - Bed sharing: the debate continues. PMID- 26991459 TI - Preparation of magnetic glycoprotein-imprinted nanoparticles with dendritic polyethyleneimine as a monomer for the specific recognition of ovalbumin from egg white. AB - Glycoproteins are crucial in massive physiological events and clinical application. It is necessary to prepare new materials to isolate the specific glycoprotein. New and simple core-shell molecularly imprinted polymers were prepared by surface imprinting. The polymers are synthesized with magnetic nanoparticles as the core, water-soluble dendritic polyethyleneimine as the monomer and the ovalbumin as the template. The prepared imprinted polymers showed thin imprinted shell, biocompatibility and superparamagnetic properties. The resultant materials exhibited fast kinetics, high adsorption capacity, perfect selectivity and reusability. More important, they can absorb the template glycoprotein from the neutral solution and successfully be applied to recognize the ovalbumin from egg white, which means that they can provide an alternate method to isolate glycoprotein from bodily fluids. PMID- 26991460 TI - Frequency of HIV testing among gay and bisexual men in the UK: implications for HIV prevention. AB - OBJECTIVES: The aim of the study was to explore HIV testing frequency among UK men who have sex with men (MSM) in order to direct intervention development. METHODS: Cross-sectional surveys were completed by 2409 MSM in Edinburgh, Glasgow and London in 2011 and a Scotland-wide online survey was carried out in 2012/13. The frequency of HIV testing in the last 2 years was measured. RESULTS: Overall, 21.2% of respondents reported at least four HIV tests and 33.7% reported two or three tests in the last 2 years, so we estimate that 54.9% test annually. Men reporting at least four HIV tests were younger and less likely to be surveyed in London. They were more likely to report higher numbers of sexual and anal intercourse partners, but not "higher risk" unprotected anal intercourse (UAI) with at least two partners, casual partners and/or unknown/discordant status partners in the previous 12 months. Only 26.7% (238 of 893) of men reporting higher risk UAI reported at least four tests. Among all testers (n = 2009), 56.7% tested as part of a regular sexual health check and 35.5% tested following a risk event. Differences were observed between surveys, and those testing in response to a risk event were more likely to report higher risk UAI. CONCLUSIONS: Guidelines recommend that all MSM test annually and those at "higher risk" test more frequently, but our findings suggest neither recommendation is being met. Additional efforts are required to increase testing frequency and harness the opportunities provided by biomedical HIV prevention. Regional, demographic and behavioural differences and variations in the risk profiles of testers suggest that it is unlikely that a "one size fits all" approach to increasing the frequency of testing will be successful. PMID- 26991462 TI - Validation of the board certification system for expert surgeons (hepato-biliary pancreatic field) using the data of the National Clinical Database of Japan: part 1 - Hepatectomy of more than one segment. AB - BACKGROUND: The objective of this study was to validate the board certification system of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) using the data of hepatectomy cases from the National Clinical Database (NCD) of Japan. METHODS: Minimal required annual numbers of high-level hepato-biliary pancreatic (HBP) surgeries were 50 for a board-certified A training institution and 30 for a board-certified B training institution. Records of 14,970 patients who had undergone hepatectomy of more than one segment (MOS), excluding lateral segmentectomy, during 2011 and 2012 were analyzed according to the category of board-certified institution and with or without participation of board-certified instructors or expert surgeons. RESULTS: Thirty-day mortality and operative mortality of 14,970 patients after MOS hepatectomy were 1.9% and 3.8%, respectively. Operative mortality rates after MOS hepatectomies performed at certified A institutions, certified B institutions, and non-certified institutions were 3.1%, 3.8%, and 4.5%, respectively (P < 0.001). The operative mortality rates after MOS hepatectomies performed with participation of certified instructors or expert surgeons were better than those without (3.5% vs. 4.3%, P = 0.012). A multiple logistic regression model showed that the cutoffs of high level HBP surgeries performed per year at hospitals that predicted operative mortality after MOS hepatectomies were 10 and 50. CONCLUSIONS: Competences and requirements for board-certified institutions, instructors, and expert surgeons to perform hepatectomy were found to be appropriate. PMID- 26991463 TI - Use of photodynamic therapy and chitosan for inactivacion of Candida albicans in a murine model. AB - BACKGROUND: The wide use of topical and systemic antifungal agents as the conventional treatment for oral candidiasis has caused Candida albicans to develop resistance to these agents. The aims of this study were to evaluate the effects of photodynamic therapy (PDT) and chitosan on buccal candidiasis and study the possible enhancive effect of chitosan on the photosensitizer methylene blue. METHODS: Thirty-five DBA/2 immunosuppressed mice were orally inoculated with a suspension of Candida albicans. The animals were randomized into seven groups (n = 5 per group): Group 1 (control); Group 2 (nystatin); Group 3 (PDT); Group 4 (chitosan 1.5 mg/ml); Group 5 (chitosan 3 mg/ml); Group 6 (PDT + chitosan 1.5 mg/ml); and Group 7 (PDT + chitosan 3 mg/ml). The Candida albicans count was evaluated on days 3, 5, 7, and 11 after inoculation. At last, macroscopic and microscopic analyses of the tongue dorsa were performed. RESULTS: On day 7 after inoculation, the control group showed a greater number of Candida albicans (5.25 +/- 0.41 log10 CFU/ml), with significant differences compared to all other groups (P <= 0.05). On day 11 after inoculation, animals treated with PDT showed lower CFU/ml count. Groups 2, 3, 4, 5, and 6 showed fewer microscopic candidiasis lesions than Groups 1 and 7. CONCLUSIONS: PDT has an antifungal effect, even greater than nystatin. Chitosan has a powerful fungicide effect but did not possess any enhancive effect on methylene blue. PMID- 26991461 TI - Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongation in vitro and promotes nerve fiber regeneration in transected spinal cord injury. AB - Extracellular matrix (ECM) expression is temporally and spatially regulated during the development of stem cells. We reported previously that fibronectin (FN) secreted by bone marrow mesenchymal stem cells (MSCs) was deposited on the surface of gelatin sponge (GS) soon after culture. In this study, we aimed to assess the function of accumulated FN on neuronal differentiating MSCs as induced by Schwann cells (SCs) in three dimensional transwell co-culture system. The expression pattern and amount of FN of differentiating MSCs was examined by immunofluorescence, Western blot and immunoelectron microscopy. The results showed that FN accumulated inside GS scaffold, although its mRNA expression in MSCs was progressively decreased during neural induction. MSC-derived neuron-like cells showed spindle-shaped cell body and long extending processes on FN decorated scaffold surface. However, after blocking of FN function by application of monoclonal antibodies, neuron-like cells showed flattened cell body with short and thick neurites, together with decreased expression of integrin beta1. In vivo transplantation study revealed that autocrine FN significantly facilitated endogenous nerve fiber regeneration in spinal cord transection model. Taken together, the present results showed that FN secreted by MSCs in the early stage accumulated on the GS scaffold and promoted the neurite elongation of neuronal differentiating MSCs as well as nerve fiber regeneration after spinal cord injury. This suggests that autocrine FN has a dynamic influence on MSCs in a three dimensional culture system and its potential application for treatment of traumatic spinal cord injury. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1902-1911, 2016. PMID- 26991464 TI - The clinical value of HPV genotyping in triage of women with high-risk-HPV positive self-samples. AB - Cytology alone, or combined with HPV16/18 genotyping, might be an acceptable method for triage in hrHPV-cervical cancer screening. Previously studied HPV genotype based triage algorithms are based on cytology performed without knowledge of hrHPV status. The aim of this study was to explore the value of hrHPV genotyping combined with cytology as triage tool for hrHPV-positive women. 520 hrHPV-positive women were included from a randomised controlled self-sampling trial on screening non-attendees (PROHTECT-3B). Eighteen baseline triage strategies were evaluated for cytology and hrHPV genotyping (Roche Cobas 4800) on physician-sampled triage material. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), referral rate, and number of referrals needed to diagnose (NRND) were calculated for CIN2+ and CIN3+. A triage strategy was considered acceptable if the NPV for CIN3+ was >=98%, combined with maintenance or improvement of sensitivity and an increase in specificity in reference to the comparator, being cytology with a threshold of atypical cells of undetermined significance (ASC-US). Three triage strategies met the criteria: HPV16+ and/or >=LSIL; HPV16+ and/or >=HSIL; (HPV16+ and/or HPV18+) and/or >=HSIL. Combining HPV16+ and/or >=HSIL yielded the highest specificity (74.9%, 95% CI 70.5-78.9), with a sensitivity (94.4%, 95% CI 89.0-97.7) similar to the comparator (93.5%, 95% CI 87.7-97.1), and a decrease in referral rate from 52.2% to 39.5%. In case of prior knowledge of hrHPV presence, triage by cytology testing can be improved by adjusting its threshold, and combining it with HPV16/18 genotyping. These strategies improve the referral rate and specificity for detecting CIN3+ lesions, while maintaining adequate sensitivity. PMID- 26991465 TI - Copolymerization of Epichlorohydrin and CO2 Using Zinc Glutarate: An Additional Application of ZnGA in Polycarbonate Synthesis. AB - The use of zinc glutarate (ZnGA) as a heterogeneous catalyst for the copolymerization of epichlorohydrin, an epoxide with an electron-withdrawing substituent, and CO2 is reported. This catalyst shows the highest selectivity (98%) for polycarbonate over the cyclic carbonate in epichlorohydrin/CO2 copolymerization under mild conditions. The (epichlorohydrin-co-CO2 ) polymer exhibits a high glass transition temperature (Tg ), 44 degrees C, which is the maximum Tg value obtained for the (epichlorohydrin-co-CO2 ) polymer to date. PMID- 26991468 TI - Treatment of primary perniosis with oral pentoxifylline (a double-blind placebo controlled randomized therapeutic trial). AB - Primary perniosis is an annoying cold-induced dermatosis. Many therapeutic agents have been tried with either unsatisfactory or controversial results. The aim of this study was to assess the efficacy of oral pentoxyfylline in the treatment of primary perniosis. A double-blind placebo-controlled randomized therapeutic study conducted in dermatology department of Al-Yarmouk Teaching Hospital, Baghdad, Iraq during four winter seasons between 2010 and 2014. The patients were randomly allocated into two equal groups: group A patients were given oral pentoxyfylline 400 mg thrice daily whereas patients in group B were given an identical placebo tablet thrice daily for 3 weeks. Therapeutic response of both groups was clinically assessed weekly for 3 weeks and side-effects were recorded. A total of 110 patients with chilblains completed this therapeutic trial. The mean age was 24.98 +/- 9.17 year. Male to female ratio was 1:2.4. All patients presented with erythematous papules, plaques or nodules. Very good therapeutic response was significantly better for group A than that of group B at 7th, 4th, and 21st days of the trial (p-value: 0.0148, 0.0000004, and 0.0000000, respectively). No side effects were encountered in both groups. Pentoxyfylline is an effective and safe drug for treatment of primary perniosis. PMID- 26991466 TI - Review: The HSP90 molecular chaperone-an enigmatic ATPase. AB - The HSP90 molecular chaperone is involved in the activation and cellular stabilization of a range of 'client' proteins, of which oncogenic protein kinases and nuclear steroid hormone receptors are of particular biomedical significance. Work over the last two decades has revealed a conformational cycle critical to the biological function of HSP90, coupled to an inherent ATPase activity that is regulated and manipulated by many of the co-chaperones proteins with which it collaborates. Pharmacological inhibition of HSP90 ATPase activity results in degradation of client proteins in vivo, and is a promising target for development of new cancer therapeutics. Despite this, the actual function that HSP90s conformationally-coupled ATPase activity provides in its biological role as a molecular chaperone remains obscure. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 594-607, 2016. PMID- 26991469 TI - Chemical Composition, Antimicrobial and Cytotoxic Activity of Heracleum verticillatum Pancic and H. ternatum Velen. (Apiaceae) Essential Oils. AB - In this work, the chemical composition, antimicrobial and cytotoxic activity of Heracleum verticillatum Pancic and H. ternatum Velen. root, leaf, and fruit essential oils were investigated. The composition was analyzed by GC and GC/MS. Heracleum verticillatum and H. ternatum root oils were dominated by monoterpenes, mostly beta-pinene (23.5% and 47.3%, respectively). Heracleum verticillatum leaf oil was characterized by monoterpenes, mainly limonene (20.3%), and sesquiterpenes, mostly (E)-caryophyllene (19.1%), while H. ternatum leaf oil by the high percentage of phenylpropanoids, with (Z)-isoelemicin (35.1%) being dominant constituent. Both fruit oils contained the majority of aliphatic esters, mostly octyl acetate (42.3% in H. verticillatum oil and 49.0% in H. ternatum oil). The antimicrobial activity of the oils was determined by microdilution method against eight bacterial and eight fungal strains. The strongest effect was exhibited by H. verticillatum root oil, particularly against Staphylococcus aureus, Salmonella typhimurium (MICs = 0.14 mg/ml, MBCs = 0.28 mg/ml), and Trichoderma viride (MIC = 0.05 mg/ml, MFC = 0.11 mg/ml). Cytotoxic effect was determined by MTT test against malignant HeLa, LS174, and A549 cells (IC50 = 5.9 146.0 MUg/ml), and against normal MRC-5 cells (IC50 > 120.1 MUg/ml). The best effect was exhibited by H. verticillatum root oil on A549 cells (IC50 = 5.9 MUg/ml), and H. ternatum root oil against LS174 cells (IC50 = 6.7 MUg/ml). PMID- 26991470 TI - Dyslipidemia associated with heavy alcohol use. AB - BACKGROUND AND OBJECTIVES: Alcohol has many effects on lipid metabolism and has been associated with elevated triglycerides. The purpose of this paper is to report a case of globally dysregulated lipids secondary to alcohol use and to describe the natural history of this phenomenon after drinking cessation. METHODS: We present a case of an otherwise healthy patient (N = 1) who was admitted to our facility for alcohol detoxification and found to have extreme lipid dysregulation. He was treated with benzodiazepines for alcohol withdrawal but no hypolipidemic agents were given. RESULTS: Lipid indices self-corrected and were found to be normal following just several weeks of sobriety in the absence of treatment with any hypolipidemic agents. DISCUSSION: The literature regarding the effects of alcohol on lipid metabolism is briefly reviewed followed by a discussion of how these findings might apply to this patient in particular as well as implications for broader clinical practice. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Alcohol has the ability to dysregulate several lipid indices in addition to elevating triglycerides. The rapid resolution of dyslipidemia suggests that additional treatment may not be necessary for patients who are able to abstain from alcohol but that hypolipidemic agents may be indicated for those patients who continue to drink. Additionally, clinicians should consider checking lipid panels in patients who present with alcohol intoxication and are found to have other laboratory abnormalites or those who have risk factors for hyperlipidemia. PMID- 26991471 TI - Clinical prognostic value of DNA methylation in hepatoblastoma: Four novel tumor suppressor candidates. AB - Hepatoblastoma (HB) is very rare but the most common malignant neoplasm of the liver occurring in children. Despite improvements in therapy, outcomes for patients with advanced HB that is refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the survival rate among this group, identification of novel prognostic markers and therapeutic targets is needed. We have previously reported that altered DNA methylation patterns are of biological and clinical importance in HB. In the present study, using genome-wide methylation analysis and bisulfite pyrosequencing with specimens from HB tumors, we detected nine methylated genes. We then focused on four of those genes, GPR180, MST1R, OCIAD2, and PARP6, because they likely encode tumor suppressors and their increase of methylation was associated with a poor prognosis. The methylation status of the four genes was also associated with age at diagnosis, and significant association with the presence of metastatic tumors was seen in three of the four genes. Multivariate analysis revealed that the presence of metastatic tumors and increase of methylation of GPR180 were independent prognostic factors affecting event-free survival. These findings indicate that the four novel tumor suppressor candidates are potentially useful molecular markers predictive of a poor outcome in HB patients, which may serve as the basis for improved therapeutic strategies when clinical trials are carried out. PMID- 26991472 TI - Effect of ATRX and G-Quadruplex Formation by the VNTR Sequence on alpha-Globin Gene Expression. AB - ATR-X (alpha-thalassemia/mental retardation X-linked) syndrome is caused by mutations in chromatin remodeler ATRX. ATRX can bind the variable number of tandem repeats (VNTR) sequence in the promoter region of the alpha-globin gene cluster. The VNTR sequence, which contains the potential G-quadruplex-forming sequence CGC(GGGGCGGGG)n , is involved in the downregulation of alpha-globin expression. We investigated G-quadruplex and i-motif formation in single-stranded DNA and long double-stranded DNA. The promoter region without the VNTR sequence showed approximately twofold higher luciferase activity than the promoter region harboring the VNTR sequence. G-quadruplex stabilizers hemin and TMPyP4 reduced the luciferase activity, whereas expression of ATRX led to a recovery in reporter activity. Our results demonstrate that stable G-quadruplex formation by the VNTR sequence downregulates the expression of alpha-globin genes and that ATRX might bind to and resolve the G-quadruplex. PMID- 26991473 TI - Free-flap salvage: muscle only versus skin paddle - an Australian experience. AB - BACKGROUND: Free-tissue transfer flaps are an effective reconstructive option for complex wounds; however, flap failure is a dreaded complication requiring timely re-exploration and salvage. The aim of this study was to determine whether salvage rates were higher in skin flaps, as opposed to muscle flaps, due to the durability of the overlying skin paddle allowing for better visual post-operative monitoring and more timely recognition of the threatened flap. METHODS: We conducted a retrospective analysis of all patients who underwent a free flap at an Australian tertiary centre between 2004 and 2014. Data were collected on patient demographics, indication, flap type, time of recognition of the threatened flap and re-exploration outcome. Data were analysed using Stata version 13 (StataCorp, College Station, TX, USA). Student's t-test, analysis of variance and Pearson's chi-squared test were used to compare groups. RESULTS: There were 560 patients who underwent 573 free flaps. The most common indication was trauma. There were 58 re-explorations with a successful salvage rate of 79.3% (46/58). Overall complete flap loss rate was 2.1% (12/573). In flaps requiring re exploration, there was a higher complete flap loss rate for muscle only flaps versus those with a skin paddle (P-value = 0.041). CONCLUSION: While timely recognition and re-exploration of the compromised free flap in the early postoperative setting is important in determining the flap salvage success, it is demonstrated that salvage rates are poorer for muscle only flaps compared with flaps with a skin paddle. PMID- 26991474 TI - Resting-state functional connectivity of the human habenula in healthy individuals: Associations with subclinical depression. AB - INTRODUCTION: The habenula (Hb) is postulated to play a critical role in reward and aversion processing across species, including humans, and has been increasingly implicated in depression. However, technical constraints have limited in vivo investigation of the human Hb, and its function remains poorly characterized. We sought to overcome these challenges by examining the whole brain resting-state functional connectivity of the Hb and its possible relationship to depressive symptomatology using the high-resolution WU-Minn Human Connectome Project (HCP) dataset. METHODS: Anatomical and resting-state functional MRI data from 50 healthy subjects with low or high subclinical depression scores (n = 25 each) were analyzed. Using novel semi-automated segmentation and optimization techniques, we generated individual-specific Hb seeds and calculated whole-brain functional connectivity for the entire cohort and the contrast of high vs. low depression groups. RESULTS: In the entire cohort, the Hb exhibited significant connectivity with key brainstem structures (i.e., ventral tegmental area, substantia nigra, pons) as well as the anterior and posterior cingulate cortices, precuneus, thalamus, and sensorimotor cortex. Multiple regions showed differential Hb connectivity based on subclinical depression scores, including the amygdala, insula, and prefrontal, mid-cingulate, and entorhinal cortices. CONCLUSIONS: Hb connectivity findings converged on areas associated with salience processing, sensorimotor systems, and the default mode network. We also detected substantial Hb-brainstem connectivity, consistent with prior histological and animal research. High and low subclinical depression groups exhibited differences in Hb connectivity with multiple regions previously linked to depression, suggesting the relationship between these structures as a potential target for future research and treatment. Hum Brain Mapp 37:2369-2384, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991477 TI - Cytology of minimal deviation endocervical adenocarcinoma (adenoma malignum) on a ThinPrep Pap test. PMID- 26991475 TI - Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis. AB - Precision medicine is defined by the National Institute of Health's Precision Medicine Initiative Working Group as an approach to disease treatment that takes into account individual variability in genes, environment, and lifestyle. There has been increased interest in applying the concept of precision medicine to idiopathic pulmonary fibrosis, in particular to search for genetic and molecular biomarker-based profiles (so called endotypes) that identify mechanistically distinct disease subgroups. The relevance of precision medicine to idiopathic pulmonary fibrosis is yet to be established, but we believe that it holds great promise to provide targeted and highly effective therapies to patients. In this manuscript, we describe the field's nascent efforts in genetic/molecular endotype identification and how environmental and behavioral subgroups may also be relevant to disease management. PMID- 26991476 TI - Facile Recoding of Selenocysteine in Nature. AB - Selenocysteine (Sec or U) is encoded by UGA, a stop codon reassigned by a Sec specific elongation factor and a distinctive RNA structure. To discover possible code variations in extant organisms we analyzed 6.4 trillion base pairs of metagenomic sequences and 24 903 microbial genomes for tRNA(Sec) species. As expected, UGA is the predominant Sec codon in use. We also found tRNA(Sec) species that recognize the stop codons UAG and UAA, and ten sense codons. Selenoprotein synthesis programmed by UAG in Geodermatophilus and Blastococcus, and by the Cys codon UGU in Aeromonas salmonicida was confirmed by metabolic labeling with (75) Se or mass spectrometry. Other tRNA(Sec) species with different anticodons enabled E. coli to synthesize active formate dehydrogenase H, a selenoenzyme. This illustrates the ease by which the genetic code may evolve new coding schemes, possibly aiding organisms to adapt to changing environments, and show the genetic code is much more flexible than previously thought. PMID- 26991479 TI - Photocatalytic Deposition of Hydroxyapatite onto a Titanium Dioxide Nanotubular Layer with Fine Tuning of Layer Nanoarchitecture. AB - A new effective method of photocatalytic deposition of hydroxyapatite (HA) onto semiconductor substrates is proposed. A highly ordered nanotubular TiO2 (TNT) layer formed on titanium via its anodization is chosen as the photoactive substrate. The method is based on photodecomposition of the phosphate anion precursor, triethylphosphate (TEP), on the semiconductor surface with the following reaction of formed phosphate anions with calcium cations presented in the solution. HA can be deposited only on irradiated areas, providing the possibility of photoresist-free HA patterning. It is shown that HA deposition can be controlled via pH, light intensity, and duration of the process. Energy dispersive X-ray spectroscopy profile analysis and glow discharge optical emission spectroscopy of HA-modified TNT prove that HA deposits over the entire TNT depth. High biocompatibility of the surfaces is proven by protein adsorption and pre-osteoblast cell growth. PMID- 26991478 TI - Factors associated with risk for assisted living among community-dwelling older Japanese. AB - OBJECTIVES: To clarify the factors associated with risk for assisted living among community-dwelling older people, we conducted a large-scale survey in an urban city in Japan. DESIGN: Population-based cross-sectional study. SETTING: A mid sized urban city in western Japan with a population of approximately 410,000. PARTICIPANTS: Nondisabled and nondemented community-dwelling older people (>=65 years). MEASUREMENTS: A self-administered postal questionnaire, including a health checklist for the screening of older people at high risk for assisted living, as well as demographic/sociodemographic questions on sex, age, present illness, living alone, duration of residence within the current city, community participation, and employment status, was distributed. RESULTS: There were 41,796 returned questionnaires (response rate: 73.8%, average age: 72.0). Participants who were at high risk for assisted living accounted for 25.2%. The independent factors associated with risk for men and women were higher age, present illness, lack of community participation, unemployment, and<20years of residence. Living alone was a significant factor for men, whereas it was insignificant among women. The types of illnesses among people at risk were different between men and women. CONCLUSION: Higher age, present illness, and several social factors were independently associated with high-risk status for assisted living in the large scale whole community survey, and there was a sex difference. Our results may provide basic information for the further application of effective preventive intervention in the community. PMID- 26991480 TI - Variation in the prion protein sequence in Dutch goat breeds. AB - Scrapie is a neurodegenerative disease occurring in goats and sheep. Several haplotypes of the prion protein increase resistance to scrapie infection and may be used in selective breeding to help eradicate scrapie. In this study, frequencies of the allelic variants of the PrP gene are determined for six goat breeds in the Netherlands. Overall frequencies in Dutch goats were determined from 768 brain tissue samples in 2005, 766 in 2008 and 300 in 2012, derived from random sampling for the national scrapie surveillance without knowledge of the breed. Breed specific frequencies were determined in the winter 2013/2014 by sampling 300 breeding animals from the main breeders of the different breeds. Detailed analysis of the scrapie-resistant K222 haplotype was carried out in 2014 for 220 Dutch Toggenburger goats and in 2015 for 942 goats from the Saanen derived White Goat breed. Nine haplotypes were identified in the Dutch breeds. Frequencies for non-wild type haplotypes were generally low. Exception was the K222 haplotype in the Dutch Toggenburger (29%) and the S146 haplotype in the Nubian and Boer breeds (respectively 7 and 31%). The frequency of the K222 haplotype in the Toggenburger was higher than for any other breed reported in literature, while for the White Goat breed it was with 3.1% similar to frequencies of other Saanen or Saanen derived breeds. Further evidence was found for the existence of two M142 haplotypes, M142 /S240 and M142 /P240 . Breeds vary in haplotype frequencies but frequencies of resistant genotypes are generally low and consequently selective breeding for scrapie resistance can only be slow but will benefit from animals identified in this study. The unexpectedly high frequency of the K222 haplotype in the Dutch Toggenburger underlines the need for conservation of rare breeds in order to conserve genetic diversity rare or absent in other breeds. PMID- 26991481 TI - Adverse event assessment and reporting in trials of newer treatments for post operative pain. AB - BACKGROUND: Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post-operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown. METHODS: We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post-operative pain for: (1) adherence to the 10 recommendations from the 'CONSORT Extension for Harms,' (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity. RESULTS: We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications. CONCLUSIONS: Considerable widespread improvements are needed in AE reporting for post-operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting. PMID- 26991482 TI - Highly recoverable TiO2-GO nanocomposites for stormwater disinfection. AB - A highly recoverable titanium dioxide-graphene oxide (TiO2-GO) composite was developed by a facile method of ultrasonic treatment of GO nanosheets and TiO2 nanoparticles, which should overcome the separation problem of nanosized TiO2 from treated water. Separability of the prepared samples was systematically investigated by gravity settling experiments. The samples' photocatalytic activity for stormwater disinfection was also studied under the irradiation of a solar simulator. The results demonstrated that TiO2-GO showed high efficient separability due to its accelerated settling behaviour. Zeta-potential analysis showed that the accelerated sedimentation of the catalyst was attributed to the aggregation of TiO2-GO resulting from the electrostatic attraction between TiO2 and GO. The TiO2-GO composite with a mass ratio of 100:2 (TiO2-2%GO) achieved both higher separability and good photocatalytic activity for stormwater disinfection. Its suspension became clear (turbidity < 50 NTU) after 8 h of sedimentation, while 99.5% of E.coli were deactivated in 90 min. The TiO2-GO composite exhibited excellent durability; no apparent change in the separability of TiO2-2%GO was observed after 10 treatment cycles (15 h in total), while only slight decrease in the photocatalytic activity was noted. In conclusion, the developed TiO2-GO composite showed promising results for stormwater disinfection. PMID- 26991483 TI - Potential Role of Long Non-Coding RNA in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells. AB - BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as important regulators of eukaryotic gene expression and have been shown to regulate various modular components of development and differentiation. However, the roles of lncRNAs in the regulation of osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) remain poorly understood. METHODS: Expression patterns of lncRNA and messenger RNA (mRNA) during osteogenic differentiation were profiled using microarray analysis. Quantitative reverse transcription polymerase chain reaction was performed to validate the microarray data. Biologic functions of candidates were revealed by: 1) cluster analysis; 2) gene ontology (GO); and 3) pathway analysis. Coding-non-coding gene coexpression (CNC) networks were constructed to investigate potential regulatory roles of lncRNAs and osteogenesis-related mRNAs. RESULTS: After osteoinduction, 3,557 mRNAs and 2,171 lncRNAs were differentially expressed, of which 994 lncRNAs were upregulated and 1,177 were downregulated (fold change >2.0 or <-2.0; P <0.05). Cluster analysis showed that lncRNAs and mRNAs from the experimental and control groups belonged to different clusters. GO analysis demonstrated that: 1) cellular process; 2) biologic regulation; and 3) regulation of biologic process were the most significant groups related to induction. Pathway analysis indicated that 83 pathways corresponded to differentially expressed mRNAs, including: 1) mitogen-activated protein kinase; 2) vascular endothelial growth factor; and 3) transforming growth factor-beta signaling pathways. CNC network analysis indicated that 393 lncRNAs were closely related to osteogenesis-related mRNAs. CONCLUSIONS: Expression profiles of lncRNAs and mRNAs were significantly altered during osteogenic differentiation of hPDLSCs. This result suggests that lncRNAs may play crucial roles in this process and could regulate mRNA expression. PMID- 26991484 TI - Hyaluronic Acid Improves Bone Formation in Extraction Sockets With Chronic Pathology: A Pilot Study in Dogs. AB - BACKGROUND: Previous studies on ridge preservation focusing on fresh extraction sockets using graft materials for ridge preservation procedures have reported a delay in the tissue modeling and remodeling phases. The objective of this study is to evaluate the effect of hyaluronic acid (HA) on healing of infected sockets. METHODS: Six beagle dogs were used in this study. Both mandibular third premolars were hemisected, and the distal roots were extracted. Subsequently, periodontal and endodontic lesions were induced at the remaining mesial root. After communication of the periodontal lesion, an endodontic periapical lesion was observed at 4 months, and the mesial roots of both the right and left sides were extracted. HA was applied into the socket of the test group, and no treatment was administered to the other group (control group). Three months after extraction of the mesial roots, the dogs were sacrificed, and histologic evaluations were performed. RESULTS: The sockets were filled by mineralized bone (47.80% +/- 6.60%) and bone marrow (50.47% +/- 6.38%) in the control group, whereas corresponding values were 63.29% +/- 9.78% and 34.73% +/- 8.97% for the test group, respectively. There was a statistically significant difference between the groups. Reversal lines and a copious lineup of osteoblasts were observed in the middle and apical parts of the sockets in the test group. CONCLUSION: An infected socket shows delayed healing of the socket wound, and HA, because of its osteoinductive, bacteriostatic, and anti-inflammatory properties, may improve bone formation and accelerate wound healing in infected sockets. PMID- 26991485 TI - Non-Surgical Periodontal Therapy Reduces Saliva Adipokine and Matrix Metalloproteinase Levels in Periodontitis. AB - BACKGROUND: Adipokines enhance the synthesis of proinflammatory cytokines and matrix metalloproteinases (MMPs), which play a role in extracellular matrix degeneration. The aim of this study is to determine the levels of some adipokines, proinflammatory cytokines, and MMPs in the saliva of patients with periodontitis and healthy individuals and to evaluate the changes after non surgical periodontal therapy (NSPT). METHODS: Of 32 individuals included in the study, 17 had periodontitis and 15 had healthy gingiva. Saliva samples were obtained from all individuals. In patients with periodontitis, samples were recollected 3 and 6 months after NSPT. Visfatin, chemerin, progranulin, interleukin (IL)-1beta, IL-8, MMP-8, and MMP-13 levels were measured using enzyme linked immunosorbent assay. RESULTS: In patients with periodontitis, all of the parameters measured in the saliva were higher than those of healthy individuals. At 3 months, visfatin, progranulin, IL-8, and MMP-8 levels were significantly decreased compared with baseline values. The levels of other biochemical parameters, chemerin and IL-1beta, were significantly decreased compared with baseline values at 6 months, and the levels became similar to those in healthy individuals. In the periodontitis group, positive correlations were found among visfatin and IL-8 (r = 0.909, P <0.01), MMP-8 (r = 0.702, P = 0.02), and MMP-13 (r = 0.781, P = 0.01); chemerin and IL-8 (r = 0.913, P <0.01), MMP-8 (r = 0.770, P <0.01), and MMP-13 (r = 0.788, P <0.01); and progranulin and IL-8 (r = 0.762, P <0.01), MMP-8 (r = 0.845, P <0.01), and MMP-13 (r = 0.813, P <0.01). CONCLUSION: Adipokines may contribute to the breakdown of periodontal tissue in periodontitis by stimulating the expression of proinflammatory cytokines and MMPs. PMID- 26991486 TI - Periodontal Status in Morbidly Obese Patients With and Without Obstructive Sleep Apnea Syndrome Risk: A Cross-Sectional Study. AB - BACKGROUND: This cross-sectional study aims to investigate the correlation between obstructive sleep apnea syndrome (OSAS) risk with periodontal disease and anthropometric measures in Class III obese patients. METHODS: Anthropometric measurements were taken from 108 patients of both sexes, aged 30 to 60 years. The Berlin questionnaire (Bq) and the Epworth sleepiness scale (ESS) were applied to determine the risk for OSAS. Full-mouth periodontal status was determined by probing depth, clinical attachment level, gingival bleeding index, and the presence of calculus. Unpaired Student t, chi(2), Fisher exact, and Mann-Whitney U tests were applied to analyze the differences between high and low risk for OSAS groups. RESULTS: Overall, 81.5% of the patients showed high risk for OSAS, 46.3% had excessive daytime sleepiness, 41.5% were positive for both the Bq and ESS, and 97.2% had periodontal disease (periodontitis = 85.2% and gingivitis = 60.2%). Patients with periodontal disease showed high risk for OSAS (82.9%) and ESS (45.7%). However, there was no influence of periodontal disease on OSAS risk. Periodontitis was not associated with the ESS (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 0.54 to 6.26) or Bq (OR = 0.87, 95% CI = 0.10 to 7.84), nor was gingivitis associated with the ESS (OR = 1.25, 95% CI = 0.48 to 3.25) or Bq (OR = 0.23, 95% CI = 0.03 to 1.84). Waist circumference (P = 0.03), neck circumference (NC, P <0.001), and the percentage of predicted NC (PPNC, P <0.001) were significantly larger in the patients at high risk for OSAS than in those at low risk for OSAS. Daytime sleepiness was also associated with NC (P = 0.02) and PPNC (P = 0.02). CONCLUSION: There was no association between periodontal disease and OSAS risk in Class III obese patients, but OSAS risk was associated with both NC and PPNC. PMID- 26991487 TI - Chemerin as a Novel Crevicular Fluid Marker of Patients With Periodontitis and Type 2 Diabetes Mellitus. AB - BACKGROUND: The objectives of the present study are to: 1) determine whether gingival crevicular fluid (GCF) chemerin is a novel predictive marker for patients with chronic periodontitis (CP) with and without type 2 diabetes mellitus (t2DM); 2) analyze the relationship between chemerin and interleukin (IL)-6 in periodontally healthy individuals and in patients with CP and with and without t2DM; and 3) evaluate the effect of non-surgical periodontal therapy on GCF chemerin levels. METHODS: Eighty individuals were split into four groups: 20 who were systemically and periodontally healthy (CTRL), 20 with t2DM and periodontally healthy (DM-CTRL), 20 systemically healthy with CP (CP), and 20 with CP and t2DM (DM-CP). Individuals with periodontitis were treated with non surgical periodontal therapy. GCF sampling procedures and clinical periodontal measures were performed before and 6 weeks after treatment. Enzyme-linked immunosorbent assay was used to measure chemerin and IL-6 levels. RESULTS: Greater values for GCF chemerin and IL-6 levels were found in CP groups than in periodontally healthy groups, in DM-CP than in CP, and in DM-CTRL than in CTRL (P <0.008). GCF chemerin and IL-6 levels decreased following therapy in CP groups (P <0.02). A comprehensive overview of all groups showed a statistically significant positive correlation of chemerin with IL-6, glycated hemoglobin, sampled-site clinical attachment level, and gingival index (P <0.05). CONCLUSIONS: In this study, periodontitis and t2DM induced aberrant secretion of chemerin, and non surgical periodontal therapy influenced the decrease of GCF chemerin levels in patients with CP with and without t2DM. Furthermore, it suggests GCF chemerin levels may be considered a potential proinflammatory marker for diabetes, periodontal disease, and treatment outcomes. PMID- 26991488 TI - Ozone Therapy Enhances Osseous Healing in Rats With Diabetes With Calvarial Defects: A Morphometric and Immunohistochemical Study. AB - BACKGROUND: Bone healing is impaired in diabetes mellitus (DM) cases. The aim of this study is to investigate, both morphometrically and immunohistochemically, the effect of gaseous ozone on bone healing in diabetic rat calvarial defects treated with xenografts. METHODS: DM was induced with 50 mg/kg intraperitoneal streptozotocin in 56 male Wistar rats. Study groups were as follows: 1) empty defect (control, n = 14); 2) xenograft (XG, n = 14); 3) empty defect treated with ozone therapy (control + ozone, n = 14); and 4) xenograft and ozone application (XG + ozone, n = 14). Critical-size defects were created in all rats. Bovine derived xenograft was applied to XG groups. Gaseous ozone was applied on the operation day and daily for 2 weeks (140 ppm at 2 L/d, 2.24 mg). Rats were sacrificed at 4 or 8 weeks post-surgery. Total bone area, newly formed bone, and residual graft material were measured histomorphometrically. Osteocalcin and bone morphogenic protein (BMP)-2 expression was evaluated immunohistochemically. RESULTS: Osteoclast numbers in the XG + ozone group were higher than the other groups at week 4 (P <0.05). XG + ozone group revealed more total bone area and new bone area than the XG group at weeks 4 (P <0.05) and 8 (P >0.05). Residual graft materials were decreased in the XG + ozone group and the same group revealed more BMP-2 positivity compared with other groups. Osteocalcin positivity in XG groups was higher than in control groups. CONCLUSION: Within the limitations of this DM animal study, gaseous ozone application accelerates xenograft resorption and enhances bone regeneration, especially in the early stages of bone healing. PMID- 26991489 TI - Relief of Injection Pain During Delivery of Local Anesthesia by Computer Controlled Anesthetic Delivery System for Periodontal Surgery: Randomized Clinical Controlled Trial. AB - BACKGROUND: Pain from local anesthetic injection makes patients anxious when visiting a dental clinic. This study aims to determine differences in pain according to types of local anesthetizing methods and to identify the possible contributing factors (e.g., dental anxiety, stress, and sex). METHODS: Thirty-one patients who underwent open-flap debridement in maxillary premolar and molar areas during treatment for chronic periodontitis were evaluated for this study. A randomized, split-mouth, single-masked clinical trial was implemented. The dental anxiety scale (DAS) and perceived stress scale (PSS) were administered before surgery. Two lidocaine ampules for each patient were used for local infiltration anesthesia (supraperiosteal injection). Injection pain was measured immediately after local infiltration anesthesia using the visual analog pain scale (VAS) questionnaire. Results from the questionnaire were used to assess degree of pain patients feel when a conventional local anesthetic technique (CNV) is used compared with a computer-controlled anesthetic delivery system (CNR). RESULTS: DAS and PSS did not correlate to injection pain. VAS scores were lower for CNR than for CNV regardless of the order in which anesthetic procedures were applied. VAS score did not differ significantly with sex. Pearson coefficient for correlation between VAS scores for the two procedures was 0.80, also indicating a strong correlation. CONCLUSION: Within the limitations of the present study, relief from injection pain is observed using CNR. PMID- 26991490 TI - Porphyromonas gingivalis Lipopolysaccharide Stimulation of Vascular Smooth Muscle Cells Activates Proliferation and Calcification. AB - BACKGROUND: Porphyromonas gingivalis (Pg) is a major etiologic agent of periodontitis, whose virulence has been attributed to different factors, including lipopolysaccharide (LPS). Vascular ectopic calcification as a well known major risk factor for adverse cardiovascular diseases is a highly prevalent vascular pathophenotype, and vascular smooth muscle cells (VSMCs) play an important role in mediating vascular calcification. It was hypothesized that Pg LPS may stimulate vascular calcification through a direct effect on VSMC function. To test this hypothesis, the effect of Pg-LPS on VSMC calcification was determined. METHODS: Primary cultures of VSMCs were obtained and identified by immunochemistry in vitro. The proliferation and alkaline phosphatase (ALP) activity of VSMCs were measured using a cell counting kit and an ALP activity test. Mineral deposition was examined using alizarin red staining. Gene (e.g. ALP, core binding factor alpha1 [Cbfalpha1], bone sialoprotein [BSP], and osteopontin [OPN]) expression levels altered by Pg-LPS were determined by reverse transcription-polymerase chain reaction array. RESULTS: Pg-LPS could increase the proliferation of VSMCs at different times and enhance ALP activity of VSMCs after 1 day. Alizarin red staining and quantification showed that, with Pg-LPS treatment, VSMCs displayed more obvious calcification nodules. When stimulated with Pg-LPS, the expression of specific osteogenic genes (e.g., ALP, Cbfalpha1, BSP, and OPN) was significantly promoted in the presence or absence of mineralization-inducing medium, whereas the expression of the OPN gene was inhibited in the mineralization induction group at day 7. CONCLUSION: Pg-LPS can stimulate VSMC calcification, which results in vascular calcification, further proving the precise relationship between periodontitis and vascular calcification. PMID- 26991491 TI - Concentrations of carbamazepine and carbamazepine-10,11-epoxide in maternal and umbilical cord blood at birth: Influence of co-administration of valproic acid or enzyme-inducing antiepileptic drugs. AB - BACKGROUND: Carbamazepine is one of the three most frequently prescribed antiepileptic drugs in pregnancy. However, data relating to both carbamazepine and carbamazepine-10,11-epoxide transplacental passage remain sparse. MATERIAL AND METHODS: We have analysed in a cohort of 114 women carbamazepine and carbamazepine-10,11-epoxide levels in maternal and umbilical cord serum at birth during 25 years retrospectively. The carbamazepine maternal apparent oral clearance, ratio of the umbilical cord/maternal level and ratio of the carbamazepine-10,11-epoxide/carbamazepine ratio were estimated. The influence of co-medication with valproic acid or enzyme-inducing antiepileptic drugs was evaluated. RESULTS: The maternal carbamazepine levels varied from 0.6 to 11.8mg/L (carbamazepine-10,11-epoxide 0.1-2.5mg/L) and in umbilical cord between 0.1 and 10.5mg/L (carbamazepine-10,11-epoxide 0.1-2.2mg/L). The ratio the of umbilical cord/maternal level of carbamazepine ranged from 0.03 to 2.23 (median 0.80) and of carbamazepine-10,11-epoxide between 0.17 and 2.00 (median 0.83). Concomitant administration with enzyme inducers significantly increased the maternal apparent oral clearance by approximately 50% and co-administration with valproic acid approximately by 70%. Combination with valproic acid significantly increased the rate of carbamazepine-10,11-epoxide to the parent drug both in maternal serum (by approximately 80%) and in umbilical cord (by 100%). CONCLUSIONS: The data showed the wide interindividual variability of the ratio of the umbilical cord/maternal level of both carbamazepine and carbamazepine-10,11-epoxide. It is the first study showing the significant increase of the ratio of umbilical cord/maternal level of carbamazepine-10,11-epoxide and carbamazepine-10,11 epoxide/carbamazepine ratio not only in maternal serum but also in umbilical cord in addition of valproic acid. The present study demonstrates that a concomitant administration of enzyme-inducing antiepileptics and valproic acid increases the maternal apparent oral clearance of carbamazepine significantly. PMID- 26991492 TI - Ursolic acid plays a protective role in obesity-induced cardiovascular diseases. AB - The metabolic disturbance of obesity is one of the most common risk factors of atherosclerosis. Resistin, an obesity-induced adipokine, can induce the expression of cell adhesion molecules and the attachment of monocytes to endothelial cells, which play an important role in the development of atherosclerosis. Ursolic acid, a pentacyclic triterpenoid found in fruits and many herbs, exhibits an array of biological effects such as anti-inflammatory and antioxidative properties. The aim of this study was to investigate the potential underlying mechanisms of the effect of ursolic acid on resistin-induced adhesion of U937 cells to human umbilical vein endothelial cells (HUVECs). Our data indicated that ursolic acid suppressed the adhesion of U937 to HUVECs and downregulated the expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and E selectin, in resistin-induced HUVECs by decreasing the production of intracellular reaction oxygen species (ROS) and attenuating the nuclear translocation of NFkappaB. Ursolic acid appeared to inhibit resistin-induced atherosclerosis, suggesting that ursolic acid may play a protective role in obesity-induced cardiovascular diseases. PMID- 26991493 TI - Geographic variation in psychotropic drug utilisation among older people in New Zealand. AB - AIM: To examine psychotropic drug utilisation in older people in New Zealand by age, sex, health board domicile and deprivation status. METHODS: A repeated cross sectional analysis of population-based drug utilisation data stratified by age, sex, ethnicity, health board and deprivation status was conducted from 2005 to 2013. RESULTS: Psychotropic utilisation increased between 2005 and 2013 (ranging from 7.0 to 74.0%) across all the health boards. In people aged 85 years and above, the hypnotic and sedative prevalence ratio compared to the 65- to 69-year age group was 1.45 (95% CI 1.44, 1.46). Between 2005 and 2013, the antidepressants prevalence ratio increased (1.27 (95% CI 1.22, 1.33)) relative to anxiolytics. CONCLUSIONS: Overall psychotropic drug utilisation increased over time. Despite safety concerns, hypnotic and sedative utilisation increased in the oldest vulnerable group. Shifts from anxiolytics to antidepressants in some health boards were consistent with guidelines for extended indications of antidepressant drug use. PMID- 26991495 TI - An Outbreak of Bartonella bacilliformis in an Endemic Andean Community. AB - BACKGROUND: Bartonellosis affects small Andean communities in Peru, Colombia and Ecuador. Research in this area has been limited. METHODS: Retrospective review of 191 cases of bartonellosis managed in Caraz District Hospital, Peru, during the last outbreak (2003). RESULTS: The majority of cases (65%) were 14 years old and younger. There was a peak in acute cases after the rainy season; chronic cases presented more constantly throughout the year. The sensitivity of blood smear against blood culture in acute disease was 25%. The most commonly used treatment for chronic disease was rifampicin; chloramphenicol was used to treat most acute cases. Complications arose in 6.8% and there were no deaths. CONCLUSIONS: Diagnostic and treatment algorithms for acute and chronic bartonellosis have been developed without a strong evidence base. Preparation of ready-to-go operational research protocols for future outbreaks would strengthen the evidence base for diagnostic and treatment strategies and enhance opportunities for control. PMID- 26991496 TI - The Value of Monitoring the Serum Concentration of Mycophenolate Mofetil in Children with Steroid-Dependent/Frequent Relapsing Nephrotic Syndrome. AB - BACKGROUND: Mycophenolate mofetil (MMF) is an alternative treatment strategy in children with steroid sensitivity who have frequent relapses or steroid-dependent nephrotic syndrome (FRNS/SDNS). METHODS: From January 2009 to January 2015, 31 cases of children with FRNS/SDNS were prospectively recruited and administered MMF and prednisone; then, serum samples were collected, and the area under the curve (AUC) of mycophenolic acid (MPA-AUC) was calculated. RESULTS: A MPA-AUC of 27.99 MUg.h/ml had a diagnostic sensitivity of 65.2% and a specificity of 87.5% in discriminating relapsing from non-relapsing patients (receiver operating characteristic-AUC 0.848). The 31 patients were then grouped according to the results of the MPA-AUC as follows: low-AUC group, <30 MUg.h/ml and high-AUC group, >=30 MUg.h/ml. The results indicated that there was a significant difference in the remission rate between the groups (x03C7;2 = 6.645, p = 0.01) during the 6 months of follow-up. Compared with the results before MMF therapy, the steroid dosage in both groups was significantly reduced at the 6- and 12 month follow-ups. Furthermore, the steroid dose was reduced more significantly in the high-AUC group than in the low-AUC group (0.447 +/- 0.254 vs. 0.219 +/- 0.161 mg/kg/day, p = 0.006) at the 6-month follow-up. Compared with the low-AUC group at the 6-month follow-up, the number of patients with relapse and relapse episodes in the high-AUC group were also significantly reduced (7/16 vs. 1/15, p = 0.037, and 15/27 vs. 1/29, p = 0.014, respectively). CONCLUSIONS: MMF is a reasonable treatment choice to reduce the number of relapse episodes and steroid administration in children with FRNS/SDNS. Moreover, children in the high-AUC group (MPA-AUC >=30 MUg.h/ml) tended to require lower steroid doses and had greater remission rates than the patients in the low-AUC group (<30 MUg.h/ml) at the 6-month follow-up. PMID- 26991494 TI - Safety and Efficacy of Botulinum Toxin to Preserve Gland Function after Radiotherapy in Patients with Head and Neck Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blinded Phase I Clinical Trial. AB - This prospective, randomized, placebo-controlled, double-blinded phase I clinical trial investigates safety and efficacy of botulinum toxin (BoNT) to preserve gland function after radiotherapy in patients with head and neck cancer. Twelve patients with advanced head and neck cancer were injected with BoNT into the submandibular glands prior to primary radiochemotherapy. Six patients received BoNT/A and 6 patients BoNT/A and B, half of each subgroup into their left and the other half into their right gland. As an internal control, sodium chloride was injected into the respective contralateral gland (placebo). For the evaluation of the salivary gland function, technetium pertechnetate salivary gland scintigraphy was performed before and after the end of radiotherapy. BoNT/A and B were well tolerated. Analysis of the scintigraphic data revealed no statistically significant difference between BoNT and placebo regarding the scintigraphic uptake difference (pBoNT/A = 0.84 and pBoNT/A-B = 0.56 for BoNT/A vs. placebo and BoNT/A-B vs. placebo, respectively). We also found no significant difference in treatment between BoNT and placebo in terms of salivary excretion fraction (pBoNT/A = 0.44; pBoNT/A-B = 0.44). This study demonstrates that BoNT can be safely combined with radiochemotherapy. Dosing and timing of BoNT injection should be further investigated for efficacy analysis. Trial Registration German Registry for Clinical Trails DRKS00004595. PMID- 26991497 TI - Comparing Risk Factor Profiles between Intracerebral Hemorrhage and Ischemic Stroke in Chinese and White Populations: Systematic Review and Meta-Analysis. AB - BACKGROUND: Chinese populations have a higher proportion of intracerebral hemorrhage (ICH) in total strokes. However, the reasons are not fully understood. METHODS: To assess the differences in frequency of major risk factors between ICH and ischemic stroke (IS) in Chinese versus white populations of European descent, we systematically sought studies conducted since 1990 that compared frequency of risk factors between ICH and IS in Chinese or white populations. For each risk factor, in Chinese and Whites separately, we calculated study-specific and random effects pooled prevalence and odds ratios (ORs) for ICH versus IS. RESULTS: Six studies among 36,190 Chinese, and seven among 52,100 white stroke patients studied hypertension, diabetes, atrial fibrillation (AF), ischemic heart disease (IHD), hypercholesterolemia, smoking and alcohol. Pooled prevalence of AF was significantly lower in Chinese. Pooled ORs for ICH versus IS were mostly similar in Chinese and Whites. However, in Chinese--but not Whites--mean age was lower (62 versus 69 years), while hypertension and alcohol were significantly more frequent in ICH than IS (ORs 1.38, 95% CI 1.18-1.62, and 1.46, 1.12-1.91). Hypercholesterolemia and smoking were significantly less frequent in ICH in Whites, but not Chinese, while IHD, AF and diabetes were less frequent in ICH in both. CONCLUSIONS: Different risk factor distributions in ICH and IS raise interesting possibilities about variation in mechanisms underlying the different distributions of pathological types of stroke between Chinese and Whites. Further analyses in large, prospective studies, including adjustment for potential confounders, are needed to consolidate and extend these findings. PMID- 26991498 TI - Discovering General Multidimensional Associations. AB - When two variables are related by a known function, the coefficient of determination (denoted R2) measures the proportion of the total variance in the observations explained by that function. For linear relationships, this is equal to the square of the correlation coefficient, rho. When the parametric form of the relationship is unknown, however, it is unclear how to estimate the proportion of explained variance equitably--assigning similar values to equally noisy relationships. Here we demonstrate how to directly estimate a generalised R2 when the form of the relationship is unknown, and we consider the performance of the Maximal Information Coefficient (MIC)--a recently proposed information theoretic measure of dependence. We show that our approach behaves equitably, has more power than MIC to detect association between variables, and converges faster with increasing sample size. Most importantly, our approach generalises to higher dimensions, estimating the strength of multivariate relationships (Y against A, B, ...) as well as measuring association while controlling for covariates (Y against X controlling for C). An R package named matie ("Measuring Association and Testing Independence Efficiently") is available (http://cran.r project.org/web/packages/matie/). PMID- 26991499 TI - Non-specific phospholipase C1 affects silicon distribution and mechanical strength in stem nodes of rice. AB - Silicon, the second abundant element in the crust, is beneficial for plant growth, mechanical strength, and stress responses. Here we show that manipulation of the non-specific phospholipase C1, NPC1, alters silicon content in nodes and husks of rice (Oryza sativa). Silicon content in NPC1-overexpressing (OE) plants was decreased in nodes but increased in husks compared to wild-type, whereas RNAi suppression of NPC1 resulted in the opposite changes to those of NPC1-OE plants. NPC1 from rice hydrolyzed phospholipids and galactolipids to generate diacylglycerol that can be phosphorylated to phosphatidic acid. Phosphatidic acid interacts with Lsi6, a silicon transporter that is expressed at the highest level in nodes. In addition, the node cells of NPC1-OE plants have lower contents of cellulose and hemicellulose, and thinner sclerenchyma and vascular bundle fibre cells than wild-type plants; whereas NPC1-RNAi plants displayed the opposite changes. These data indicate that NPC1 modulates silicon distribution and secondary cell wall deposition in nodes and grains, affecting mechanical strength and seed shattering. PMID- 26991501 TI - Transforming Clinical Data into Actionable Prognosis Models: Machine-Learning Framework and Field-Deployable App to Predict Outcome of Ebola Patients. AB - BACKGROUND: Assessment of the response to the 2014-15 Ebola outbreak indicates the need for innovations in data collection, sharing, and use to improve case detection and treatment. Here we introduce a Machine Learning pipeline for Ebola Virus Disease (EVD) prognosis prediction, which packages the best models into a mobile app to be available in clinical care settings. The pipeline was trained on a public EVD clinical dataset, from 106 patients in Sierra Leone. METHODS/PRINCIPAL FINDINGS: We used a new tool for exploratory analysis, Mirador, to identify the most informative clinical factors that correlate with EVD outcome. The small sample size and high prevalence of missing records were significant challenges. We applied multiple imputation and bootstrap sampling to address missing data and quantify overfitting. We trained several predictors over all combinations of covariates, which resulted in an ensemble of predictors, with and without viral load information, with an area under the receiver operator characteristic curve of 0.8 or more, after correcting for optimistic bias. We ranked the predictors by their F1-score, and those above a set threshold were compiled into a mobile app, Ebola CARE (Computational Assignment of Risk Estimates). CONCLUSIONS/SIGNIFICANCE: This method demonstrates how to address small sample sizes and missing data, while creating predictive models that can be readily deployed to assist treatment in future outbreaks of EVD and other infectious diseases. By generating an ensemble of predictors instead of relying on a single model, we are able to handle situations where patient data is partially available. The prognosis app can be updated as new data become available, and we made all the computational protocols fully documented and open sourced to encourage timely data sharing, independent validation, and development of better prediction models in outbreak response. PMID- 26991502 TI - INTRAOCULAR LENS SCAFFOLD TO PREVENT INTRAOCULAR FOREIGN BODY SLIPPAGE. AB - PURPOSE: To report the application of intraocular lens (IOL) scaffold technique in intraocular foreign body (IOFB) removal. METHODS: Patient with IOFB in posterior segment is included. The IOFB is retrieved from the posterior segment (pars plana vitrectomy and exteriorization of the IOFB from the retinal surface using an intravitreal forceps via the posterior capsulotomy) and placed on the iris. A three-piece posterior chamber IOL is placed in the sulcus via the clear corneal incision. IOFB is then removed from the anterior chamber over the IOL by forceps. RESULTS: Metallic IOFB of 4 mm * 3 mm has been retrieved by IOL scaffold technique after rescuing it from the posterior segment. There has been no drop or slip of IOFB in the vitreous during removal. Posterior chamber IOL served as scaffold during IOFB removal from anterior chamber. CONCLUSION: The IOL scaffold maneuver has shown to prevent slippage by acting as a barrier between the IOFB and the vitreous. PMID- 26991500 TI - Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults. AB - BACKGROUND: Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. METHODS: As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18-30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. RESULTS: We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000-170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. CONCLUSIONS: Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients. PMID- 26991503 TI - Systematic review with meta-analysis: Lactobacillus reuteri DSM 17938 for diarrhoeal diseases in children. AB - BACKGROUND: Not all probiotics are equal. AIM: To investigate the efficacy of Lactobacillus reuteri DSM 17938 (L. reuteri) in the management of various types of diarrhoeal diseases in children. METHODS: Medline, Embase, the Cochrane Library, trial registries and reference lists of included studies were searched in January 2016, with no language restriction, for randomised controlled trials (RCTs). RESULTS: Eight RCTs (n = 1229) met the inclusion criteria. In treatment trials, L. reuteri administration reduced the duration of diarrhoea (three RCTs, n = 256, mean difference, MD -24.82 h, 95% CI -38.8 to -10.8) and increased the cure rate on day 1 and day 2. However, heterogeneity and wide confidence intervals call for caution in interpreting results. In preventive trials carried out in hospitalised children, based on the findings from two RCTs (n = 290), there was no significant reduction in the risk of nosocomial diarrhoea, rotavirus diarrhoea or diarrhoea of any origin with L. reuteri administration. Based on one RCT (n = 97), there was no effect of L. reuteri on the risk of antibiotic associated diarrhoea. However, the evidence is limited because the overall frequency of diarrhoea was surprisingly low. In preventive studies carried out in apparently healthy children, L. reuteri reduced diarrhoeal outcomes in one RCT; the evidence from another trial was less convincing. CONCLUSIONS: In therapeutic settings, L. reuteri administration reduces the duration of diarrhoea and increases the chance of cure. In preventive settings, L. reuteri has the potential to reduce the risk of community-acquired diarrhoea in otherwise healthy children. PMID- 26991504 TI - Direct Phase Equilibrium Simulations of NIPAM Oligomers in Water. AB - NIPAM (N-isopropylacrylamide)-based polymers in water show many interesting properties in experiments, including a lower critical solution temperature (LCST) at 305 K and a conformational transition of single chains at the same temperature. The results of many simulation studies suggest that standard force fields are able to describe the conformational transition and the phase equilibrium well. We show by performing long molecular dynamics simulations of the direct liquid-liquid phase equilibrium of NIPAM trimers in water that there is no LCST in the expected temperature range for any of the force fields under study. The results show further that the relaxation times of single-chain simulations are considerably longer than anticipated. Conformational transitions of single polymers can therefore not necessarily be used as surrogates for a real phase transition. PMID- 26991506 TI - Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations. AB - In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991505 TI - Changing pattern of dengue virus serotypes circulating during 2008-2012 and reappearance of dengue serotype 3 may cause outbreak in Kolkata, India. AB - Dengue virus infection is a major cause of morbidity within the endemic tropical and subtropical regions of the world. Dengue virus has four distinct serotypes with specific clinical manifestations. In this study, we observed the changing pattern of dengue serotypes, age-wise dengue infection and useful sero-detection methods needed in a dengue endemic region. We identified dengue serotypes during a period of 5 years among patients with dengue symptoms visiting one of the largest tertiary care infectious disease hospitals of eastern India in Kolkata. A total of 433 dengue RNA positive samples were isolated from 712 acute dengue suspected cases. Age wise distribution highlighted the susceptible age group being >21 years (24.02%) followed by 11-15 years (21.71%) and 5-10 years (21.02%) of the total infected population. Higher numbers of infected cases were found within females as they are involved in more indoor works. The period of study experienced two dengue outbreaks one in 2008 and another in 2012. For early dengue detection, NS1 was found to be more confirmatory than IgM ELISA regarding sensitivity and specificity. DENV-1, 2, and 4 serotypes were the common circulating strains from 2008 until 2010, after which DENV-3 serotype infections rise and led to a massive dengue outbreak in Kolkata with increased numbers of DHF and DSS cases in 2012. The finding within our study emphasizes the public health importance of such prospective surveillance programs with respect to the changing dengue viral etiology and serotypes. J. Med. Virol. 88:1697-1702, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991507 TI - Novel Dystonia Genes: Clues on Disease Mechanisms and the Complexities of High Throughput Sequencing. AB - Dystonia is a genetically heterogenous disease and a prototype disorder where next-generation sequencing has facilitated the identification of new pathogenic genes. This includes the first two genes linked to recessively inherited isolated dystonia, that is, HPCA (hippocalcin) and COL6A3 (collagen VI alpha 3). These genes are proposed to underlie cases of the so-called DYT2-like dystonia, while also reiterating two distinct pathways in dystonia pathogenesis. First, deficiency in HPCA function is thought to alter calcium homeostasis, a mechanism that has previously been forwarded for CACNA1A and ANO3. The novel myoclonus dystonia genes KCTD17 and CACNA1B also implicate abnormal calcium signaling in dystonia. Second, the phenotype in COL6A3-loss-of-function zebrafish models argues for a neurodevelopmental defect, which has previously been suggested as a possible biological mechanism for THAP1, TOR1A, and TAF1 based on expression data. The newly reported myoclonus-dystonia gene, RELN, plays also a role in the formation of brain structures. Defects in neurodevelopment likewise seem to be a recurrent scheme underpinning mainly complex dystonias, for example those attributable to biallelic mutations in GCH1, TH, SPR, or to heterozygous TUBB4A mutations. To date, it remains unclear whether dystonia is a common phenotypic outcome of diverse underlying disease mechanisms, or whether the different genetic causes converge in a single pathway. Importantly, the relevance of pathways highlighted by novel dystonia genes identified by high-throughput sequencing depends on the confirmation of mutation pathogenicity in subsequent genetic and functional studies. However, independent, careful validation of genetic findings lags behind publications of newly identified genes. We conclude with a discussion on the characteristics of true-positive reports. PMID- 26991508 TI - Brief Report: A web-based pilot study of childhood sexual abuse, recent stressful events, and alcohol use in women. AB - BACKGROUND AND OBJECTIVES: Childhood sexual abuse (CSA) is a well-documented risk factor for problem drinking, but the possibility that recent stressful events exacerbate risk conferred by CSA has rarely been examined, and the few studies to do so have limited their investigations to negative events. The aim of the current study was to examine the associations between CSA, recent positive and negative stressful events, and women's alcohol consumption. METHODS: Eighty-nine women (42.7% reporting CSA) completed weekly web-based alcohol use surveys and a stressful event inventory assessing negative and positive events over a 12 week period. RESULTS: Independent of CSA history, experiencing negative events was associated with elevated likelihood of drinking to intoxication. DISCUSSION AND CONCLUSIONS: Proximal distressing events are more closely linked than CSA history to short-term drinking patterns. SCIENTIFIC SIGNIFICANCE: Tracking stressful negative events may be informative for identifying precipitants of heavy drinking. PMID- 26991509 TI - Physiological, biochemical and molecular characterization of an induced mutation conferring imidazolinone resistance in wheat. AB - The Clearfield((r)) wheat cultivars possessing imidazolinone (IMI)-resistant traits provide an efficient option for controlling weeds. The imazamox-resistant cultivar Pantera (Clearfield((r)) ) was compared with a susceptible cultivar (Gazul). Target and non-target mechanisms of resistance were studied to characterize the resistance of Pantera and to identify the importance of each mechanism involved in this resistance. Pantera is resistant to imazamox as was determined in previous experiments. The molecular study confirmed that it carries a mutation Ser-Asn627 conferring resistance to imazamox in two out of three acetolactate synthase (ALS) genes (imi1 and imi2), located in wheat on chromosomes 6B and 6D, respectively. However, the last gene (imi3) located on chromosome 6A does not carry any mutation conferring resistance. As a result, photosynthetic activity and chlorophyll content were reduced after imazamox treatment. Detoxification was higher in the resistant biotype as shown by metabolomic study while imazamox translocation was higher in the susceptible cultivar. Interestingly, imazamox metabolism was higher at higher doses of herbicide, which suggests that the detoxification process is an inducible mechanism in which the upregulation of key gene coding for detoxification enzymes could play an important role. Thus, the identification of cultivars with a higher detoxification potential would allow the development of more resistant varieties. PMID- 26991510 TI - Shoot tolerance mechanisms to iron toxicity in rice (Oryza sativa L.). AB - Iron toxicity frequently affects lowland rice and leads to oxidative stress via the Fenton reaction. Tolerance mechanisms were investigated in contrasting genotypes: the intolerant IR29 and the tolerant recombinant inbred line FL483. Seedlings were exposed to 1000 mg L-1 ferrous iron, and the regulation of genes involved in three hypothetical tolerance mechanisms was investigated (I) Iron uptake, partitioning and storage. The iron concentration and speciation in different plant tissues did not differ significantly between genotypes. Sub cellular iron partitioning genes such as vacuolar iron transporters or ferritin showed no genotypic differences. (II) Antioxidant biosynthesis. Only one gene involved in carotenoid biosynthesis showed genotypic differences, but carotenoids are unlikely to scavenge the reactive oxygen species (ROS) involved in Fe toxicity, i.e. H2 O2 and hydroxyl radicals. (III) Enzymatic activities for ROS scavenging and antioxidants turnover. In shoots, glutathione-S-transferase and ascorbate oxidase genes showed genotypic differences, and consistently, the tolerant FL483 had lower dehydroascorbate reductase and higher ascorbate oxidase activity, suggesting that high rates ascorbate reduction confer sensitivity. This hypothesis was confirmed by application of exogenous reduced ascorbate or L galactono-1,4-lactone, which increased lipid peroxidation under iron toxic conditions. Our results demonstrate in planta pro-oxidant activity of reduced ascorbate in the presence of iron. PMID- 26991511 TI - A Nitrogen-Assisted One-Pot Heteroaryl Ketone Synthesis from Carboxylic Acids and Heteroaryl Halides. AB - A practical and highly effective one-pot synthesis of versatile heteroaryl ketones directly from carboxylic acids and heteroaryl halides under mild conditions is reported. This method does not require derivatization of carboxylic acids (preparation of acid chlorides, Weinreb amides, etc.) or the use of any additives/catalysts. A wide substrate scope of carboxylic acids with high functional group tolerance has also been demonstrated. The results reveal that the presence of an alpha-nitrogen on the halide substrate greatly improves the desired ketone formation. PMID- 26991512 TI - Allergic reactions in red tattoos: Raman spectroscopy for 'fingerprint' detection of chemical risk spectra in tattooed skin and culprit tattoo inks. AB - AIM: The aim of this study was to assess the feasibility of Raman spectroscopy as a screening technique for chemical characterisation of tattoo pigments in pathologic reacting tattoos and tattoo ink stock products to depict unsafe pigments and metabolites of pigments. MATERIALS/METHODS: Twelve dermatome shave biopsies from allergic reactions in red tattoos were analysed with Raman spectroscopy (A 785-nm 300 mW diode laser). These were referenced to samples of 10 different standard tattoo ink stock products, three of these identified as the culprit inks used by the tattooist and thus by history the source of the allergy. Three primary aromatic amine (PAA) laboratory standards (aniline, o-anisidine and 3,3'-dichlorobenzidine) were also studied. RESULTS: Application of Raman spectroscopy to the shave biopsies was technically feasible. In addition, all ten inks and the three PAA standards could be discriminated. 10/12 shave biopsies provided clear fingerprint Raman signals which differed significantly from background skin, and Raman spectra from 8/12 biopsies perfectly matched spectra from the three culprit ink products. The spectrum of one red ink (a low cost product named 'Tattoo', claimed to originate from Taiwan, no other info on label) was identified in 5/12 biopsies. Strong indications of the inks 'Bright Red' and 'Crimson Red' were seen in three biopsies. The three PAA's could not be unambiguously identified. CONCLUSION: This study, although on a small-scale, demonstrated Raman spectroscopy to be feasible for chemical analysis of red pigments in allergic reactions. Raman spectroscopy has a major potential for fingerprint screening of problematic tattoo pigments in situ in skin, ex vivo in skin biopsies and in tattoo ink stock products, thus, to eliminate unsafe ink products from markets. PMID- 26991513 TI - Effect of Socioeconomic Status on the Linkage Between Suicidal Ideation and Suicide Attempts. AB - Previous suicide attempts are a leading risk factor for completed suicide. To identify specific characteristics of those at high risk for attempts, we investigated associations with socioeconomic status (SES). Data from the 2013 Korean Community Health Survey (KCHS) included adults who reported suicidal ideation (N = 220,245). Attempts in the past 12 months were assessed. Associations of demographic, socioeconomic, and suicide-related behavioral factors were analyzed using multiple logistic regression. Among those with suicidal ideation, 862 (3.9%) had attempted suicide. After stratification by age and gender, results showed that low education and unemployed young adult men and women had significantly higher rates of attempts. The lowest income level was associated with significantly higher rates of attempts in only young adult women. Among those with the lowest and highest income, the association between ideation and attempts was attenuated, whereas it was enhanced among other income groups. PMID- 26991514 TI - Trends and Characteristics of United States Out-of-Hospital Births 2004-2014: New Information on Risk Status and Access to Care. AB - BACKGROUND: Out-of-hospital births are increasing in the United States. Our purpose was to examine trends in out-of-hospital births from 2004 to 2014, and to analyze newly available data on risk status and access to care. METHODS: Newly available data from the revised birth certificate for 47 states and Washington, DC, were used to examine out-of-hospital births by characteristics and to compare them with hospital births. Trends from 2004 to 2014 were also examined. RESULTS: Out-of-hospital births increased by 72 percent, from 0.87 percent of United States births in 2004 to 1.50 percent in 2014. Compared with mothers who had hospital births, those with out-of-hospital births had lower prepregnancy obesity (12.5% vs 25.0%) and smoking (2.8% vs 8.5%) rates, and higher college graduation (39.3% vs 30.0%) and breastfeeding initiation (94.3% vs 80.8%) rates. Among planned home births, 67.1 percent were self-paid, compared with 31.9 percent of birth center and 3.4 percent of hospital births. Vaginal births after cesarean (VBACs) comprised 4.6 percent of planned home births and 1.6 percent of hospital and birth center births. Sociodemographic and medical risk status of out-of hospital births improved substantially from 2004 to 2014. CONCLUSIONS: Improvements in risk status of out-of-hospital births from 2004 to 2014 suggest that appropriate selection of low-risk women is improving. High rates of self-pay for the costs of out-of-hospital birth suggest serious gaps in insurance coverage, whereas higher-than-average rates of VBAC could reflect lack of access to hospital VBACs. Mandating private insurance and Medicaid coverage could substantially improve access to out-of-hospital births. Improving access to hospital VBACs might reduce the number of out-of-hospital VBACs. PMID- 26991515 TI - Gilch Synthesis of Poly(ortho-Phenylene Vinylenes): A Powerful Access to High Molecular-Weight Blue-Emitting Polymers. AB - For the first time, the successful Gilch synthesis of poly(ortho-phenylene vinylenes) (ortho-PPVs) is reported. The molar mass of the constitutionally homogeneous ortho-PPVs reaches values as high as Mw ~ 300 000 Da. The ortho connectivity of the repeating units forces the chains to assume closely packed conformations even in good solvents. Significant perturbation of the pi-electron systems and considerable shortening of the conjugation lengths are the consequences. UV-vis absorption and photoluminescence maxima consequently are shifted clearly toward shorter wavelengths compared to, e.g., classic para-PPVs. PMID- 26991516 TI - Amelanotic malignant melanoma of the uterine cervix diagnosed by cervical smear. AB - The melanocytic cells of the cervical epithelium are capable of forming the complete spectrum of melanocytic lesions, from benign lentigines to melanoma. Primary malignant melanoma of the uterine cervix is a rare neoplasm with aggressive behavior. The absence of melanin pigment can lead to misdiagnosis as carcinomas, sarcomas, or lymphoma. Immunohistochemical studies should be used for confirmation. In order to consent the cervix as a primary site, exclusion of any other probable primary sites of melanoma is needed. Here, we present a 61-year old female patient with postmenopausal vaginal bleeding. After cervical smear, diagnosis was confirmed by cervical punch biopsy. Diagn. Cytopathol. 2016;44:535 537. (c) 2016 Wiley Periodicals, Inc. PMID- 26991517 TI - Therapeutic protein-drug interaction assessment for daclizumab high-yield process in patients with multiple sclerosis using a cocktail approach. AB - AIMS: To characterize the potential effect of daclizumab high-yield process (DAC HYP), a monoclonal antibody that blocks the high-affinity interleukin-2 receptors for treatment of multiple sclerosis, on activity of cytochrome P450 (CYP) enzymes. METHODS: Twenty patients with multiple sclerosis received an oral cocktail of probe substrates of CYP1A2 (caffeine 200 mg), CYP2C9 (warfarin 10 mg/vitamin K 10 mg), CYP2C19 (omeprazole 40 mg), CYP2D6 (dextromethorphan 30 mg) and CYP3A (midazolam 5 mg) on two sequential occasions: 7 days before and 7 days after subcutaneous administration of DAC HYP 150 mg every 4 weeks for three doses. Serial pharmacokinetic blood samples up to 96 h post dose and 12-h urine samples were collected on both occasions. Area under the curve (AUC) for caffeine, S-warfarin, omeprazole and midazolam, and urine dextromethorphan to dextrorphan ratio were calculated. Statistical analyses were conducted on log transformed parameters using a linear mixed-effects model. RESULTS: The 90% confidence intervals (CIs) for the geometric mean ratio (probe substrate with DAC HYP/probe substrate alone) for caffeine AUC from 0-12 h (0.93-1.15), S-warfarin AUC from 0 to infinity (AUC[0-inf]) (0.95-1.06), omeprazole AUC(0-inf) (0.88 1.13) and midazolam AUC(0-inf) (0.89-1.15) were within the no-effect boundary of 0.80-1.25. The geometric mean ratio for urine dextromethorphan to dextrorphan ratio was 1.01, with the 90% CI (0.76-1.34) extending slightly outside the no effect boundary, likely due to high variability with urine collections and CYP2D6 activity. CONCLUSIONS: DAC HYP treatment in patients with multiple sclerosis had no effect on CYP 1A2, 2C9, 2C19, 2D6 and 3A activity. PMID- 26991518 TI - Larva-mediated chalkbrood resistance-associated single nucleotide polymorphism markers in the honey bee Apis mellifera. AB - Chalkbrood is a disease affecting honey bees that seriously impairs brood growth and productivity of diseased colonies. Although honey bees can develop chalkbrood resistance naturally, the details underlying the mechanisms of resistance are not fully understood, and no easy method is currently available for selecting and breeding resistant bees. Finding the genes involved in the development of resistance and identifying single nucleotide polymorphisms (SNPs) that can be used as molecular markers of resistance is therefore a high priority. We conducted genome resequencing to compare resistant (Res) and susceptible (Sus) larvae that were selected following in vitro chalkbrood inoculation. Twelve genomic libraries, including 14.4 Gb of sequence data, were analysed using SNP finding algorithms. Unique SNPs derived from chromosomes 2 and 11 were analysed in this study. SNPs from resistant individuals were confirmed by PCR and Sanger sequencing using in vitro reared larvae and resistant colonies. We found strong support for an association between the C allele at SNP C2587245T and chalkbrood resistance. SNP C2587245T may be useful as a genetic marker for the selection of chalkbrood resistance and high royal jelly production honey bee lines, thereby helping to minimize the negative effects of chalkbrood on managed honey bees. PMID- 26991519 TI - Efficacy and safety of cryobiopsy versus forceps biopsy for interstitial lung diseases and lung tumours: A systematic review and meta-analysis. AB - Forceps biopsy (FB) is the most commonly used diagnostic tool for lung pathologies. FB is associated with a high diagnostic failure rate. Cryobiopsy (CB) is a novel technique providing a larger specimen size, few artefacts, more alveolar parts and superior diagnostic yield. CB, however, has drawbacks such as higher bleeding and pneumothorax rate. We conducted a meta-analysis to investigate the specimen area, diagnostic rate and bleeding severity in CB versus FB in interstitial lung diseases (ILDs) and lung tumours. A systematic literature search of PUBMED, BIOSIS PREVIEW and OVID databases was conducted using specific search terms. Eligible studies including RCTs and non-RCTs comparing cryobiopsy/cryotransbronchial biopsy (CB/CTBB) and forceps biopsy/forceps transbronchial biopsy (FB/FTBB) for specimen area, diagnostic rate and bleeding rate in ILDs and lung tumours were analysed. Two reviewers independently extracted data and evaluated the quality of the studies. Eight studies involving 916 patients were analysed. Specimen area (mm(2) ) was significantly larger in CB/CTBB than FB/FTBB (standard mean difference = 1.21, 95% confidence interval (0.94, 1.48), P < 0.00001). The diagnostic rate was significantly higher in CB/CTBB than FB/FTBB (Risk ratio 1.36, 95% confidence interval (1.16, 1.59), P = 0.0002). Three studies compared the bleeding severity with only one showing significantly more bleeding in CB. Cryobiopsy/cryotransbronchial shows superiority to FB/FTBB for specimen area and diagnostic rate. CB/CTBB has better efficacy over FB/FTBB. PMID- 26991520 TI - "Third-Generation"-Type Functional Tris(2-pyridyl)borate Ligands and Their Transition-Metal Complexes. AB - Phenyltris(2-pyridyl)borates (Tpyb) are a promising class of tripodal "scorpionate"-type ligands with potential utility in the development of transition-metal complexes with interesting optical, electronic, or magnetic properties and as building blocks to metallosupramolecular polymers. We report here a new class of "third-generation"-type Tpyb ligands that contain different functional groups attached to the boron-bound aryl moiety. The synthesis, characterization, and metal-ion complexation behavior of ligands with iodo and trimethylsilyl groups are discussed. The electrochemical and absorption characteristics of the corresponding low-spin iron(II) and ruthenium(II) complexes are compared. We demonstrate the further elaboration of iodo derivatives with alkynes via Sonogashira-Hagihara coupling, a process that proceeds with high yield for the iron(II) and ruthenium(II) complexes but not for the free ligand. Borylation of the silyl-substituted ruthenium(II) complex with BBr3 was also investigated. In addition to the expected borylation product Ru(Tpyb-Bpin)2, the replacement of one (major product) or two phenyl groups is observed, suggesting that electrophilic borylation occurs at both the C(Ph)-Si and the C(Ph)-B aromatic carbon atoms. The successful attachment of a range of different functional groups at the periphery of the Tpyb metal complexes is expected to provide opportunities to access new polymeric materials via C-C coupling or click-type reactions. PMID- 26991521 TI - Efficacy of intralesional immunotherapy for the treatment of warts: A review of the literature. AB - Warts are common epidermal growths caused by human papillomavirus that often cause significant discomfort and embarrassment. Current treatment options include topical therapies, cryotherapy, laser vaporization, and surgical excision. Many of these options are destructive and may result in scarring, while less aggressive approaches can lead to lesion recurrence. Additionally, these local modalities are not practical for patients with a large number of warts. Systemic approaches such as immunotherapy have demonstrated success in treating multiple lesions by combining a targeted approach with upregulation of the host immune system. An extensive literature review was performed to evaluate the various vaccine antigens that have been used intralesionally to treat cutaneous and anogenital warts. The specific intralesional immunotherapies that have been studied include: Candida albicans; measles, mumps, and rubella; Trichophyton; and tuberculin antigens such as purified protein derivative, Mycobacterium w vaccine, and Bacillus Calmette-Guerin. Intralesional vaccine injection represents a safe, effective, and tolerable treatment for warts, including recalcitrant and anogenital warts. This approach has been somewhat overlooked in the past despite substantial evidence of high response rates with a low side effect profile. Large comparative trials are necessary to determine the most effective immunotherapy treatment option as well as the most appropriate dosing parameters. PMID- 26991522 TI - Glucagon-like peptide-1 and vitamin D: anti-inflammatory response in diabetic kidney disease in db/db mice and in cultured endothelial cells. AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone that stimulates insulin secretion and may affect the inflammatory pathways involved in diabetes mellitus. Calcitriol, an active form of vitamin D, plays an important role in renal, endothelial and cardiovascular protection. We evaluated the anti inflammatory and histologic effects of a GLP-1 analogue (liraglutide) and of calcitriol in a db/db mouse diabetes model and in endothelial cells exposed to a diabetes-like environment. METHODS: Diabetic db/db mice were treated with liraglutide and calcitriol for 14 weeks, after which the kidneys were perfused and removed for mRNA and protein analysis and histology. Endothelial cells were stimulated with advanced glycation end products (AGEs), glucose, liraglutide and calcitriol. Total RNA and protein were extracted and analysed for the expression of selected inflammatory markers. RESULTS: Typical histological changes, glomerular enlargement and mesangial expansion were seen in db/db mice compared with control mice. Glomerular hypertrophy was ameliorated with liraglutide, compared with db/db controls. Liraglutide up-regulated endothelial nitric oxide synthase protein expression compared with the db/db control group and down regulated p65 protein expression. Calcitriol did not further improve the beneficial effect observed on protein expression. In endothelial cells, liraglutide treatment exhibited a dose-dependent ability to prevent an inflammatory response in the selected markers: thioredoxin-interacting protein, p65, IL6 and IL8. In most gene and protein expressions, addition of calcitriol did not enhance the effect of liraglutide. CONCLUSIONS: The GLP-1 analogue liraglutide prevented the inflammatory response observed in endothelial cells exposed to a diabetes-like environment and in db/db mice at the level of protein expression and significantly ameliorated the glomerular hypertrophy seen in the diabetic control group. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991523 TI - Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis? AB - The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graft-versus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign and malignant oral conditions. Here, we discuss a possible mechanistic rationale that addresses the activation of this important signaling pathway and its downstream events, while correlating it with the carcinogenic potential of chronic oral disorders. PMID- 26991524 TI - The Frontier of Molecular Spintronics Based on Multiple-Decker Phthalocyaninato Tb(III) Single-Molecule Magnets. AB - Ever since the first example of a double-decker complex (SnPc2) was discovered in 1936, MPc2 complexes with pi systems and chemical and physical stabilities have been used as components in molecular electronic devices. More recently, in 2003, TbPc2 complexes were shown to be single-molecule magnets (SMMs), and researchers have utilized their quantum tunneling of the magnetization (QTM) and magnetic relaxation behavior in spintronic devices. Herein, recent developments in Ln(III) Pc-based multiple-decker SMMs on surfaces for molecular spintronic devices are presented. In this account, we discuss how dinuclear Tb(III)-Pc multiple-decker complexes can be used to elucidate the relationship between magnetic dipole interactions and SMM properties, because these complexes contain two TbPc2 units in one molecule and their intramolecular Tb(III)-Tb(III) distances can be controlled by changing the number of stacks. Next, we focus on the switching of the Kondo signal of Tb(III)-Pc-based multiple-decker SMMs that are adsorbed onto surfaces, their characterization using STM and STS, and the relationship between the molecular structure, the electronic structure, and the Kondo resonance of Tb(III)-Pc multiple-decker complexes. PMID- 26991525 TI - Simultaneous multi-angular relaxometry of tissue with MRI (SMART MRI): Theoretical background and proof of concept. AB - PURPOSE: Accurate measurement of tissue-specific relaxation parameters is an ultimate goal of quantitative MRI. The objective of this study is to introduce a new technique, simultaneous multiangular relaxometry of tissue with MRI (SMART MRI), which provides naturally coregistered quantitative spin density, longitudinal and transverse relaxation rate constant maps along with parameters characterizing magnetization transfer (MT) effects. THEORY AND METHODS: SMART MRI is based on a gradient-recalled echo MRI sequence with multiple flip angles and multiple gradient echoes and a derived theoretical expression for the MR signal generated in this experimental conditions. The theory, based on Bloch-McConnell equations, takes into consideration cross-relaxation between two water pools: "free" and "bound" to macromolecules. It describes the role of cross-relaxation effects in formation of longitudinal and transverse relaxation of "free" water signal, thus providing background for measurements of these effects without using MT pulses. Bayesian analysis is used to optimize SMART MRI sequence parameters. RESULTS: Data obtained on three participants demonstrate feasibility of the proposed approach. CONCLUSION: SMART MRI provides quantitative measurements of longitudinal and transverse relaxation rate constants of "free" water signal affected by cross-relaxation effects. It also provides information on some essential MT parameters without requiring off-resonance MT pulses. Magn Reson Med 77:1296-1306, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26991526 TI - Perianal CD assessment surgery. PMID- 26991528 TI - Self-reported financial burden of cancer care and its effect on physical and mental health-related quality of life among US cancer survivors. AB - BACKGROUND: Cancer-related financial burden has been linked to cancer survivors (CS) forgoing/delaying medical care, skipping follow-up visits, and discontinuing medications. To the authors' knowledge, little is known regarding the effect of financial burden on the health-related quality of life of CS. METHODS: The authors analyzed 2011 Medical Expenditure Panel Survey data. Financial burden was present if one of the following problems was reported: borrowed money/declared bankruptcy, worried about paying large medical bills, unable to cover the cost of medical care visits, or other financial sacrifices. The following outcomes were evaluated: Physical Component Score (PCS) and Mental Component Score (MCS) of the 12-Item Short-Form Health Survey (SF-12), depressed mood, psychological distress, and worry related to cancer recurrence. The authors also assessed the effect of the number of financial problems on these outcomes. RESULTS: Of the 19.6 million CS analyzed, 28.7% reported financial burden. Among them, the average PCS (42.3 vs 44.9) and MCS (48.1 vs 52.1) were lower for those with financial burden versus those without. In adjusted analyses, CS with financial burden had significantly lower PCS (beta = -2.45), and MCS (beta = -3.05), had increased odds of depressed mood (odds ratio, 1.95), and were more likely to worry about cancer recurrence (odds ratio, 3.54). Survivors reporting >= 3 financial problems reported statistically significant and clinically meaningful differences (>=3 points) in the mean PCS and MCS compared with survivors without financial problems. CONCLUSIONS: Cancer-related financial burden was associated with lower health related quality of life, increased risk of depressed mood, and a higher frequency of worrying about cancer recurrence among CS. PMID- 26991527 TI - Acute Molecular Changes in Synovial Fluid Following Human Knee Injury: Association With Early Clinical Outcomes. AB - OBJECTIVE: To investigate whether molecules found to be up-regulated within hours of surgical joint destabilization in the mouse are also elevated in the analogous human setting of acute knee injury, how this molecular response varies between individuals, and whether it is related to patient-reported outcomes in the 3 months after injury. METHODS: Seven candidate molecules were analyzed in blood and synovial fluid (SF) from 150 participants with recent structural knee injury at baseline (<8 weeks from injury) and in blood at 14 days and 3 months following baseline. Knee Injury and Osteoarthritis Outcome Score 4 (KOOS4 ) was obtained at baseline and 3 months. Patient and control samples were compared using Meso Scale Discovery platform assays or enzyme-linked immunosorbent assay. RESULTS: Six of the 7 molecules were significantly elevated in human SF immediately after injury: interleukin-6 (IL-6), monocyte chemotactic protein 1, matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), activin A, and tumor necrosis factor-stimulated gene 6 (TSG-6). There was low-to-moderate correlation with blood measurements. Three of the 6 molecules were significantly associated with baseline KOOS4 (those with higher SF IL-6, TIMP-1, or TSG-6 had lower KOOS4 ). These 3 molecules, MMP-3, and activin A were all significantly associated with greater improvement in KOOS4 over 3 months, after adjustment for other relevant factors. Of these, IL-6 alone significantly accounted for the molecular contribution to baseline KOOS4 and change in KOOS4 over 3 months. CONCLUSION: Our findings validate relevant human biomarkers of tissue injury identified in a mouse model. Analysis of SF rather than blood more accurately reflects this response. The response is associated with patient-reported outcomes over this early period, with SF IL-6 acting as a single representative marker. Longitudinal outcomes will determine if these molecules are biomarkers of subsequent disease risk. PMID- 26991529 TI - Vasopressin and Oxytocin: Conductors of the Symphony of Physiology and Behaviour. PMID- 26991530 TI - Primary splenic abscess requiring splenectomy. PMID- 26991531 TI - Acrolein metabolites, diabetes and insulin resistance. AB - Acrolein is a dietary and environmental pollutant that has been associated in vitro to dysregulate glucose transport. We investigated the association of urinary acrolein metabolites N-acetyl-S-(3-hydroxypropyl)-l-cysteine (3-HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) and their molar sum (?acrolein) with diabetes using data from investigated 2027 adults who participated in the 2005 2006 National Health and Nutrition Examination Survey (NHANES). After excluding participants taking insulin or other diabetes medication we, further, investigated the association of the compounds with insulin resistance (n=850), as a categorical outcome expressed by the homeostatic model assessment (HOMA IR>2.6). As secondary analyses, we investigated the association of the compounds with HOMA-IR, HOMA-beta, fasting insulin and fasting plasma glucose. The analyses were performed using urinary creatinine as independent variable in the models, and, as sensitivity analyses, the compounds were used as creatinine corrected variables. Diabetes as well as insulin resistance (defined as HOMA-IR>2.6) were positively associated with the 3-HPMA, CEMA and ?Acrolein with evidence of a dose response relationship (p<0.05). The highest 3rd and 4th quartiles of CEMA compared to the lowest quartile were significantly associated with higher HOMA IR, HOMA-beta and fasting insulin with a dose-response relationship. The highest 3rd quartile of 3-HPMA and ?Acrolein were positively and significantly associated with HOMA-IR, HOMA-beta and fasting insulin. These results suggest a need of further studies to fully understand the implications of acrolein with type 2 diabetes and insulin. PMID- 26991532 TI - ALDH1A3, a metabolic target for cancer diagnosis and therapy. AB - Metabolism reprogramming has been linked with the initiation, metastasis, and recurrence of cancer. The aldehyde dehydrogenase (ALDH) family is the most important enzyme system for aldehyde metabolism. The human ALDH family is composed of 19 members. ALDH1A3 participates in various physiological processes in human cells by oxidizing all-trans-retinal to retinoic acid. ALDH1A3 expression is regulated by many factors, and it is associated with the development, progression, and prognosis of cancers. In addition, ALDH1A3 influences a diverse range of biological characteristics within cancer stem cells and can act as a marker for these cells. Thus, growing evidence indicates that ALDH1A3 has the potential to be used as a target for cancer diagnosis and therapy. PMID- 26991533 TI - Kidney CLC-K chloride channels inhibitors: structure-based studies and efficacy in hypertension and associated CLC-K polymorphisms. AB - OBJECTIVE: Alterations in the handling of renal salt reabsorption may contribute to interindividual differences in blood pressure regulation and susceptibility to hypertension. CLC-K chloride channels and their accessory subunit barttin play a pivotal role in kidney by controlling chloride and water absorption. Compounds selective for CLC-Ks, such as the benzofuran derivative MT-189, may have a significant therapeutic potential. Here, we assessed the feasibility of using CLC K blockers in hypertension and aimed at enhancing drug inhibitory affinity. METHODS AND RESULTS: We demonstrated that acute in-vivo administration of MT-189 to spontaneously hypertensive rats (SHR) caused a reduction of blood pressure and defined the CLC-K/barttin gene expression pattern in kidney of SHR in comparison with normotensive Wistar-Kyoto rats. Based on MT-189, we designed and tested a new series of benzofuran derivatives on CLC-K chloride channels heterologously expressed in HEK293 cells. These studies enabled us to elucidate the causative molecular relationship for obtaining the most potent and selective inhibitor (SRA 36) described so far, with an IC50 of 6.6 +/- 1 MUmol/l. The biophysical and pharmacological characterization of A447T CLC-Ka and Y315F CLC-Ka, both polymorphisms associated with hypertension, showed that SRA-36 is an efficacious inhibitor of the chloride currents sustained by these polymorphisms. Molecular docking studies allowed hypothesizing an inhibition mechanism for the considered ligands, laying the foundations for the rational design of new and more effective CLC-K inhibitors. CONCLUSION: The SRA-36 molecule represents a new potential therapeutic option for hypertension. PMID- 26991535 TI - Infection Rates Following Buttonhole Cannulation in Hemodialysis Patients. AB - Arteriovenous fistula (AVF) is the preferred access for hemodialysis (HD). Buttonhole (BH) needling has increased following the introduction of "blunt" fistula needles. Although some reported advantages for BH needling, others have reported increased infection risk. As such we reviewed our center practice, and the effect of both nasal screening and eradication and re-education and training programs. We audited the outcomes of 881 HD patients dialyzed between November 2009 and May 2012, divided into three groups: 175 dialyzing exclusively by central venous catheter (CVC), 478 exclusively by area needling AVF (AVF) and 219 by BH. There were 31 Staphylococcus aureus bacteremias (SABs); 14 (45.2%) dialyzing with CVCs, 12 (38.7%) BH and five (16.1%) AVF. The 30 day mortality rate for SAB was 7.5% with a complication rate of 22.6%. The hazard ratio for first SAB was significantly greater for both CVC and BH access compared to AVF (5.3 (95% CI -1.9-18.6), P < 0.001 and 3.6 (1.3-96), P = 0.011, respectively). During the study SAB rates per 1000 CVC days were 0.21, compared to 0.15 for BH. After major re-education and asepsis technique campaigns the SAB rate for BH fell to 0.06, but quickly returned to 0.17. Extending BH needling to all our dialysis centers, SAB infection rates increased to those not dissimilar to CVC access. Despite re-education programs coupled with a strict asepsis policy and active SA eradication, followed by audit cycles, the increased infection risk with BH remained, such that we have limited BH to self-care patients. PMID- 26991534 TI - Changes in hypertension prevalence, awareness, treatment, and control rates in Turkey from 2003 to 2012. AB - OBJECTIVES: The study aimed to assess the current epidemiology of hypertension, including its prevalence, the awareness of the condition and its treatment and control, in Turkey to evaluate changes in these factors over the last 10 years by comparing the results with the prevalence, awareness, treatment, and control of hypertension in Turkey (PatenT) study data (2003), as well as to assess parameters affecting awareness and the control of hypertension. METHODS: The PatenT 2 study was conducted on a representative sample of the Turkish adult population (n = 5437) in 2012. Specifically trained staff performed the data collection. Hypertension was defined as mean SBP or DBP at least 140/90 mmHg, previously diagnosed disease or the use of antihypertensive medication. Awareness and treatment were assessed by self-reporting, and control was defined as SBP/DBP less than 140/90 mmHg. RESULTS: Although the prevalence of hypertension in the PatenT and PatenT 2 surveys was stable at approximately 30%, hypertension awareness, treatment, and control rates have improved in Turkey. Overall, 54.7% of hypertensive patients were aware of their diagnosis in 2012 compared with 40.7% in 2003. The hypertension treatment rate increased from 31.1% in 2003 to 47.4% in 2012, and the control rate in hypertensives increased from 8.1% in 2003 to 28.7% in 2012. The rate of hypertension control in treated patients improved between 2003 (20.7%) and 2012 (53.9%). Awareness of hypertension was positively associated with older age, being a woman, residing in an urban area, a history of parental hypertension, being a nonsmoker, admittance by a physician, presence of diabetes mellitus, and being obese or overweight; it was inversely associated with a higher amount of daily bread consumption. Factors associated with better control of hypertension were younger age, female sex, residing in an urban area, and higher education level in Turkey. CONCLUSION: Although some progress has been made in recognizing hypertension from 2003 to 2012, there is still a large population of untreated or inadequately treated hypertensives in Turkey. Strengthening of population-based efforts to improve the prevention, early detection, and treatment of hypertension is needed. PMID- 26991536 TI - Experiences of informational needs and received information following a prenatal diagnosis of congenital heart defect. AB - OBJECTIVE: To explore the need for information and what information was actually received following prenatal diagnosis of a congenital heart defect, in a country where termination of pregnancy beyond 22 weeks of gestation is not easily possible because of legal constraints. METHODS: Twenty-six Swedish-speaking pregnant women (n = 14) and partners (n = 12) were consecutively recruited for semi-structured telephone interviews following the prenatal diagnosis of a congenital heart defect. Data were analyzed using content analysis. RESULTS: Although high satisfaction with the specialist information was described, the information was considered overwhelming and complex. Objective, honest, and detailed information about multiple subjects were needed, delivered repeatedly, and supplemented by written information/illustrations. Eighteen respondents had used the Internet to search for information and identified issues involving searching difficulties, low quality, and that it was too complex, insufficient, or unspecific. Those who terminated their pregnancy criticized that there was a lack of information about termination of pregnancy, both from health professionals and online sources, resulting in unanswered questions and unpreparedness. CONCLUSION: Individuals faced with a prenatal diagnosis of a congenital heart defect need individualized and repeated information. These needs are not all adequately met, as individuals are satisfied with the specialist consultation but left with unanswered questions regarding pregnancy termination. (c) 2016 John Wiley & Sons, Ltd. PMID- 26991537 TI - The increasing burden of nonalcoholic fatty liver disease among young adults in the United States: A growing epidemic. PMID- 26991538 TI - Denture-induced stomatitis and associated factors in a group of patients attending a university dental hospital in Sri Lanka. AB - AIM: The aim of the present study was to investigate factors associated with denture-induced stomatitis (DIS) among denture wearers and their oral and hand carriage of Candida. METHODS: Sociodemographics and denture and oral hygiene practices were investigated using an interviewer-administered questionnaire in denture wearers with DIS (n = 60) and without DIS (n = 60) selected using a convenience sampling of patients attending the Department of Prosthetic Dentistry, University of Peradeniya, Sri Lanka. Denture and oral hygiene practices and denture quality were scored. DIS and denture hygiene were classified. Oral and hand carriage of Candida was assessed. RESULTS: Middle-aged females were more prone to DIS. The most common DIS pattern was Newton type IotaIota. The mean age of existing denture of DIS patients was significantly higher than the control. Denture hygiene practice was significantly low in DIS patients. Poor denture hygiene practice and sleep wear of dentures were significantly associated with DIS. The risk of Candida hand carriage in a DIS patient carrying oral Candida was significantly higher than the risk of Candida hand carriage in a healthy denture wearer who carried oral Candida. CONCLUSION: Old dentures, poor denture hygiene, and sleep wear of dentures might contribute to DIS. Oral Candida in denture wearers could lead to Candida hand carriage. PMID- 26991539 TI - Changing testosterone had no direct effect on HbA1c or weight in diabetic men when TRT was interrupted and then resumed. PMID- 26991541 TI - Nutrient assessment of olive leaf residues processed by solid-state fermentation as an innovative feedstuff additive. AB - AIMS: Olive leaf residue feedstuff additives were prepared by solid-state fermentation (SSF), and its feeding effects on broiler chickens were examined. METHODS AND RESULTS: The fermentation's nutrient value, that is, protein enrichment, cellulase activity, tannic acid degradation and amino acid enhancement, was determined. The effect of different strains, including molds (Aspergillus niger, Aspergillus oryzae and Trichoderma viride) and yeasts (Candida utilis, Candida tropicalis and Geotrichum candidum), and the fermentation time on the nutrient values of the feedstuff additives was investigated. The experimental results showed that the optimal parameters for best performance were A. niger and C. utilis in a 1 : 1 ratio (v/v) in co-culture fermentation for 5 days. Under these conditions, the total content of amino acids in the fermented olive leaf residues increased by 22.0% in comparison with that in the raw leaf residues. Both Glutamic acid and Aspartic acid contents were increased by more than 25.4%. Broiler chickens fed with different amounts of feedstuff additives were assessed. The results demonstrated that the chicken weight gains increased by 120%, and normal serum biochemical parameters were improved significantly after 10% of the feedstuff additives were supplemented to the daily chicken feed for 28 days. CONCLUSIONS: The co-culture combination of A. niger and C. utilis with SSF for olive leaf residue had the best nutrient values. The addition of 10% fermented olive leaf residue facilitated the chicken growth and development. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reveals that olive leaf residues fermented by SSF exhibited considerable potential as feed additives for feeding poultry. PMID- 26991540 TI - Suppressive action of miRNAs to ARP2/3 complex reduces cell migration and proliferation via RAC isoforms in Hirschsprung disease. AB - Hirschsprung disease (HSCR) is a congenital disorder caused by the defective function of the embryonic enteric neural crest. The impaired migration of embryonic enteric neural crest plays an important role in the pathogenesis of this disease. Recent studies showed that the ARP2/3 complex and RAC isoforms had effects on actin cytoskeleton remodelling, which contributes to migration. Moreover, some regulatory relationships were identified between ARP2/3 complex and RAC isoforms. Although microRNAs (miRNAs) have been known to modulate target gene expression on the post-transcriptional level, little is known about the regulation among miRNAs, ARP2/3 complex and RAC isoforms. Here, we report that down-regulation of ARP2 and ARP3, two main subunits of ARP2/3 complex, suppressed migration and proliferation in 293T and SH-SY5Y cell lines via the inhibition of RAC1 and RAC2. Meanwhile, as the target genes, ARP2 and ARP3 are reduced by increased miR-24-1* and let-7a*, respectively, in 70 HSCR samples as compared with 74 normal controls. Co-immunoprecipitation showed that aberrant reduction in ARP2 and ARP3 could weaken the function of ARP2/3 complex. Our study demonstrates that the miR-24-1*/let-7a*-ARP2/3 complex-RAC isoforms pathway may represent a novel pathogenic mechanism for HSCR. PMID- 26991542 TI - Intuitive eating is inversely associated with body weight status in the general population-based NutriNet-Sante study. AB - OBJECTIVE: To examine the relationship between intuitive eating (IE), which includes eating in response to hunger and satiety cues rather than emotional cues and without having forbidden foods, and weight status in a large sample of adults. METHODS: A total of 11,774 men and 40,389 women aged >=18 years participating in the NutriNet-Sante cohort were included in this cross-sectional analysis. Self-reported weight and height were collected as well as IE levels using the validated French version of the Intuitive Eating Scale-2. The association between IE and weight status was assessed using multinomial logistic regression models. RESULTS: A higher IE score was strongly associated with lower odds of overweight or obesity in both men and women. The strongest associations were observed in women for both overweight [quartile 4 vs. 1 of IE: odds ratio, 95% confidence interval: (0.19, 0.17-0.20)] and obesity (0.09, 0.08-0.10). Associations in men were as follows: for overweight (0.43, 0.38-0.48) and obesity (0.14, 0.11-0.18). CONCLUSIONS: IE is inversely associated with overweight and obesity which supports its importance. Although no causality can be inferred from the reported associations, these data suggest that IE might be relevant for obesity prevention and treatment. PMID- 26991543 TI - Transparent Aluminium Oxide Coatings of Polymer Brushes. AB - A novel method for the preparation of transparent Al2O3 coatings of polymers is presented. An environmental-friendly sol-gel method is employed, which implies mild conditions and low costs. A thermoresponsive brush is chosen as a model surface. X-ray photoelectron spectroscopy is used to characterize the samples during the conversion of the precursor Al(OH)3 into oxide and to prove the mildness of the protocol. The study evidences a relation between lateral homogeneity of alumina and the wettability of the polymer surface by the precursor solution, while morphology and elasticity are dominated by the polymer properties. The study of the swelling behavior of the underneath brush reveals the absence of water uptake, proving the impermeability of the alumina layer. The broad chemical and structural variety of polymers, combined with the robustness of transparent alumina films, makes these composites promising as biomedical implants, protective sheets and components for electric and optical devices. PMID- 26991544 TI - A GABAergic tecto-tegmento-tectal pathway in pigeons. AB - Previous studies have demonstrated that the optic tecta of the left and right brain halves reciprocally inhibit each other in birds. In mammals, the superior colliculus receives inhibitory gamma-aminobutyric acid (GABA)ergic input from the basal ganglia via both the ipsilateral and the contralateral substantia nigra pars reticulata (SNr). This contralateral SNr projection is important in intertectal inhibition. Because the basal ganglia are evolutionarily conserved, the tectal projections of the SNr may show a similar pattern in birds. Therefore, the SNr could be a relay station in an indirect tecto-tectal pathway constituting the neuronal substrate for the tecto-tectal inhibition. To test this hypothesis, we performed bilateral anterograde and retrograde tectal tracing combined with GABA immunohistochemistry in pigeons. Suprisingly, the SNr has only ipsilateral projections to the optic tectum, and these are non-GABAergic. Inhibitory GABAergic input to the contralateral optic tectum arises instead from a nearby tegmental region that receives input from the ipsilateral optic tectum. Thus, a disynaptic pathway exists that possibly constitutes the anatomical substrate for the inhibitory tecto-tectal interaction. This pathway likely plays an important role in attentional switches between the laterally placed eyes of birds. J. Comp. Neurol. 524:2886-2913, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991545 TI - Conditional gene deletion with DiCre demonstrates an essential role for CRK3 in Leishmania mexicana cell cycle regulation. AB - Leishmania mexicana has a large family of cyclin-dependent kinases (CDKs) that reflect the complex interplay between cell cycle and life cycle progression. Evidence from previous studies indicated that Cdc2-related kinase 3 (CRK3) in complex with the cyclin CYC6 is a functional homologue of the major cell cycle regulator CDK1, yet definitive genetic evidence for an essential role in parasite proliferation is lacking. To address this, we have implemented an inducible gene deletion system based on a dimerised Cre recombinase (diCre) to target CRK3 and elucidate its role in the cell cycle of L. mexicana. Induction of diCre activity in promastigotes with rapamycin resulted in efficient deletion of floxed CRK3, resulting in G2/M growth arrest. Co-expression of a CRK3 transgene during rapamycin-induced deletion of CRK3 resulted in complementation of growth, whereas expression of an active site CRK3(T178E) mutant did not, showing that protein kinase activity is crucial for CRK3 function. Inducible deletion of CRK3 in stationary phase promastigotes resulted in attenuated growth in mice, thereby confirming CRK3 as a useful therapeutic target and diCre as a valuable new tool for analyzing essential genes in Leishmania. PMID- 26991546 TI - Using propensity score adjustment method in genetic association studies. AB - BACKGROUND: The statistical tests for single locus disease association are mostly under-powered. If a disease associated causal single nucleotide polymorphism (SNP) operates essentially through a complex mechanism that involves multiple SNPs or possible environmental factors, its effect might be missed if the causal SNP is studied in isolation without accounting for these unknown genetic influences. In this study, we attempt to address the issue of reduced power that is inherent in single point association studies by accounting for genetic influences that negatively impact the detection of causal variant in single point association analysis. In our method we use propensity score (PS) to adjust for the effect of SNPs that influence the marginal association of a candidate marker. These SNPs might be in linkage disequilibrium (LD) and/or epistatic with the target-SNP and have a joint interactive influence on the disease under study. We therefore propose a propensity score adjustment method (PSAM) as a tool for dimension reduction to improve the power for single locus studies through an estimated PS to adjust for influence from these SNPs while regressing disease status on the target-genetic locus. The degree of freedom of such a test is therefore always restricted to 1. RESULTS: We assess PSAM under the null hypothesis of no disease association to affirm that it correctly controls for the type-I-error rate (<0.05). PSAM displays reasonable power (>70%) and shows an average of 15% improvement in power as compared with commonly-used logistic regression method and PLINK under most simulated scenarios. Using the open-access multifactor dimensionality reduction dataset, PSAM displays improved significance for all disease loci. Through a whole genome study, PSAM was able to identify 21 SNPs from the GAW16 NARAC dataset by reducing their original trend-test p-values from within 0.001 and 0.05 to p-values less than 0.0009, and among which 6 SNPs were further found to be associated with immunity and inflammation. CONCLUSIONS: PSAM improves the significance of single-locus association of causal SNPs which have had marginal single point association by adjusting for influence from other SNPs in a dataset. This would explain part of the missing heritability without increasing the complexity of the model due to huge multiple testing scenarios. The newly reported SNPs from GAW16 data would provide evidences for further research to elucidate the etiology of rheumatoid arthritis. PSAM is proposed as an exploratory tool that would be complementary to other existing methods. A downloadable user friendly program, PSAM, written in SAS, is available for public use. PMID- 26991547 TI - Correlations of Medial Joint Space Width on Fixed-Flexed Standing Computed Tomography and Radiographs With Cartilage and Meniscal Morphology on Magnetic Resonance Imaging. AB - OBJECTIVE: To assess whether medial tibiofemoral joint space width (JSW) on 3 dimensional (3-D) standing computed tomography (SCT) correlates more closely with magnetic resonance imaging cartilage morphology (CM) and meniscal scores than does radiographic 2-D JSW. METHODS: Participants in the Multicenter Osteoarthritis Study, who had standing fixed-flexion posteroanterior knee radiographs, were recruited. Medial tibiofemoral 3-D JSW on SCT and 2-D JSW on fixed-flexion radiographs were compared with medial tibiofemoral cartilage and meniscal morphology using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations between the area of the articular surface with 3-D JSW <2.5 mm on SCT, radiographic minimal 2-D JSW, and the WORMS-CM and meniscal scores were assessed using Spearman's rho. RESULTS: For the 19 participants included (33 knees), mean +/- SD age was 66.9 +/- 5.4 years, body mass index was 29.5 +/- 4.4 kg/m(2) , 42.1% of participants were female, and the Kellgren/Lawrence grades were 0 (21.2%), 1 (36.4%), 2 (18.2%), and 3 (24.2%). The articular surface area with 3-D JSW <2.5 mm on SCT correlated with WORMS-CM scores for the central medial tibia (rs = 0.84, P < 0.001), central medial femur (rs = 0.60, P < 0.007), and posterior medial meniscal tear (rs = 0.39, P < 0.026), as did other cut points for 3-D JSW. Correlations with radiographic minimal 2-D JSW were 0.66, -0.52, and -0.40, respectively, differing from SCT only for tibial cartilage (P = 0.001). CONCLUSION: Greater surface area with a low JSW, measured by SCT, correlates more strongly with the severity of tibial cartilage lesions, while correlating with medial femoral cartilage and meniscal damage to a similar extent as radiographic minimal JSW. SCT may enable valid stratification of participants in clinical trials, through quickly and inexpensively characterizing osteoarthritis features. PMID- 26991548 TI - Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma. AB - Lymph node (LN) macrophages play critical roles in anti-tumor immunity, which develops via the activation of cytotoxic T cells (CTL) and NK cells. The present study aims to determine the prognostic significance of CD169(+) LN macrophages in patients with endometrial carcinoma (EC). The number of CD169(+) cells or the CD169(+) -to-CD68(+) macrophage ratio in regional LN (RLN), and the number of CD8(+) CTL or CD57(+) NK cells in tumor tissues were investigated by immunohistochemistry in paraffin-embedded tissue samples from 79 patients with EC. A high density of CD169(+) cells in the RLN of patients with EC was correlated with an early clinical stage or no LN metastasis. A high number of CD169(+) cells and a high CD169(+) -to-CD68(+) macrophage ratio were significantly associated with longer overall survival in EC. We also found that the density of CD169(+) macrophages was positively correlated with the number of CD8(+) CTL and CD57(+) NK cells that infiltrated into tumor tissues. A high density of CD57(+) cells in EC tissues was associated with a better prognosis, while a high density of CD8(+) cells was not linked to an altered prognosis. The present study showed that the density of CD169(+) macrophages in RLN was associated with an improved prognosis in EC patients. CD169(+) macrophages in RLN might represent a useful marker for assessing clinical prognoses and monitoring anti-tumor immunity in patients with EC. PMID- 26991549 TI - Chiral quantum supercrystals with total dissymmetry of optical response. AB - Since chiral nanoparticles are much smaller than the optical wavelength, their enantiomers show little difference in the interaction with circularly polarized light. This scale mismatch makes the enhancement of enantioselectivity in optical excitation of nanoobjects a fundamental challenge in modern nanophotonics. Here we demonstrate that a strong dissymmetry of optical response from achiral nanoobjects can be achieved through their arrangement into chiral superstructures with the length scale comparable to the optical wavelength. This concept is illustrated by the example of the simple helix supercrystal made of semiconductor quantum dots. We show that this supercrystal almost fully absorbs light with one circular polarization and does not absorb the other. The giant circular dichroism of the supercrystal comes from the formation of chiral bright excitons, which are the optically active collective excitations of the entire supercrystal. Owing to the recent advances in assembly and self-organization of nanocrystals in large superparticle structures, the proposed principle of enantioselectivity enhancement has great potential of benefiting various chiral and analytical methods, which are used in biophysics, chemistry, and pharmaceutical science. PMID- 26991550 TI - Predictable Heating and Positive MRI Contrast from a Mesoporous Silica-Coated Iron Oxide Nanoparticle. AB - Iron oxide nanoparticles have great potential as diagnostic and therapeutic agents in cancer and other diseases; however, biological aggregation severely limits their function in vivo. Aggregates can cause poor biodistribution, reduced heating capability, and can confound their visualization and quantification by magnetic resonance imaging (MRI). Herein, we demonstrate that the incorporation of a functionalized mesoporous silica shell can prevent aggregation and enable the practical use of high-heating, high-contrast iron oxide nanoparticles in vitro and in vivo. Unmodified and mesoporous silica-coated iron oxide nanoparticles were characterized in biologically relevant environments including phosphate buffered saline, simulated body fluid, whole mouse blood, lymph node carcinoma of prostate (LNCaP) cells, and after direct injection into LNCaP prostate cancer tumors in nude mice. Once coated, iron oxide nanoparticles maintained colloidal stability along with high heating and relaxivity behaviors (SARFe = 204 W/g Fe at 190 kHz and 20 kA/m and r1 = 6.9 mM(-1) s(-1) at 1.4 T). Colloidal stability and minimal nonspecific cell uptake allowed for effective heating in salt and agarose suspensions and strong signal enhancement in MR imaging in vivo. These results show that (1) aggregation can lower the heating and imaging performance of magnetic nanoparticles and (2) a coating of functionalized mesoporous silica can mitigate this issue, potentially improving clinical planning and practical use. PMID- 26991552 TI - Treatment of advanced canine anal sac adenocarcinoma with hypofractionated radiation therapy: 77 cases (1999-2013). AB - Currently no standard of care exists for advanced, inoperable or metastatic anal sac adenocarcinoma (ASAC). The objective of this retrospective study was to assess the role of hypofractionated radiation therapy (RT) in 77 dogs with measurable ASAC. A total of 38% of dogs experienced a partial response to RT. For dogs presenting with clinical signs related to the tumour, improvement or resolution of signs was noted in 63%. For dogs presenting with hypercalcemia of malignancy, resolution was noted in 31% with RT alone and an additional 46% with radiation, prednisone, and/or bisphosphonates. Median overall survival was 329 days (range: 252-448 days). Median progression free survival was 289 days (range: 224-469). There was no difference in survival based on radiation protocol, use of chemotherapy, previous surgery or advanced stage. Radiation toxicities were mild and infrequent. Hypofractionated RT is well tolerated and is applicable in the treatment of advanced primary, locoregional or metastatic ASAC. PMID- 26991551 TI - Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide induced oxidative damages in cultured rat astrocytes. AB - Astroglial cells possess an array of cellular defense mechanisms, including superoxide dismutase (SOD) and catalase antioxidant enzymes, to prevent damages caused by oxidative stress. Nevertheless, astroglial cell viability and functionality can be affected by significant oxidative stress. We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent glioprotective agent that prevents hydrogen peroxide (H2 O2 )-induced apoptosis in cultured astrocytes. The purpose of this study was to investigate the potential protective effect of PACAP against oxidative-generated alteration of astrocytic antioxidant systems. Incubation of cells with subnanomolar concentrations of PACAP inhibited H2 O2 -evoked reactive oxygen species accumulation, mitochondrial respiratory burst, and caspase-3 mRNA level increase. PACAP also stimulated SOD and catalase activities in a concentration-dependent manner, and counteracted the inhibitory effect of H2 O2 on the activity of these two antioxidant enzymes. The protective action of PACAP against H2 O2 -evoked inhibition of antioxidant systems in astrocytes was protein kinase A, PKC, and MAP-kinase dependent. In the presence of H2 O2 , the SOD blocker NaCN and the catalase inhibitor 3-aminotriazole, both suppressed the protective effects of PACAP on SOD and catalase activities, mitochondrial function, and cell survival. Taken together, these results indicate that the anti-apoptotic effect of PACAP on astroglial cells can account for the activation of endogenous antioxidant enzymes and reduction in respiration rate, thus preserving mitochondrial integrity and preventing caspase-3 expression provoked by oxidative stress. Considering its powerful anti-apoptotic and anti-oxidative properties, the PACAPergic signaling system should thus be considered for the development of new therapeutical approaches to cure various pathologies involving oxidative neurodegeneration. We propose the following cascade for the glioprotective action of Pituitary adenylate cyclase-activating polypeptide (PACAP) against H2 O2 -induced astrocyte damages and cell apoptosis in cultured rat astrocytes. PACAP, through activation of its receptor, PAC1-R, and the protein kinase A (PKA), protein kinase C (PKC), and MAP-kinases signaling pathways, prevents accumulation of ROS and inhibition of SOD and catalase activities. This allows the preservation of mitochondrial membrane integrity and the reduction in caspase-3 activation induced by H2 O2 . These data may lead to the development of new strategies for cerebral injury treatment. Cat, catalase; Cyt. C, cytochrome C; SOD, superoxide dismutase. PMID- 26991553 TI - Maturation promoting factor destabilization facilitates postovulatory aging mediated abortive spontaneous egg activation in rat. AB - The present study was designed to investigate whether destabilization of maturation promoting factor (MPF) leads to postovulatory aging-mediated abortive spontaneous egg activation (SEA). If so, we wished to determine whether changes in Wee-1 as well as Emi2 levels are associated with MPF destabilization during postovulatory aging-mediated abortive SEA in rats eggs aged in vivo. For this purpose, sexually immature female rats were given a single injection (20 IU IM) of pregnant mare serum gonadotropin for 48 h followed by single injection of human chorionic gonadotropin (20 IU). Ovulated eggs were collected after 14, 17, 19 and 21 h post-hCG surge to induce postovulatory aging in vivo. The morphological changes, Wee1, phosphorylation status of cyclin dependent kinase 1(Cdk1), early mitotic inhibitor 2 (Emi2), anaphase promoting complex/cyclosome (APC/C), cyclin B1, mitotic arrest deficient protein (MAD2) levels and Cdk1 activity were analyzed. The increased Wee 1 level triggered phosphorylation of Thr-14/Tyr-15 and dephosphorylation of Thr-161 residues of Cdk1. The decrease of Emi2 level was associated with increased APC/C level and decreased cyclin B1 level. Changes in phosphorylation status of Cdk1 and reduced cyclin B1 level resulted in destabilization of MPF. The destabilized MPF finally led to postovulatory aging-mediated abortive SEA in rat eggs. It was concluded that the increase of Wee 1 but decrease of Emi2 level triggers MPF destabilization and thereby postovulatory aging-mediated abortive SEA in rat eggs. PMID- 26991554 TI - Electrical remodeling after cardiac resynchronization therapy and its relationship with the anatomical remodeling. PMID- 26991555 TI - Effect of dipeptidyl peptidase-4 inhibitors on heart failure: A meta-analysis of randomized clinical trials. AB - BACKGROUND: Recent studies have suggested that dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) may be associated with increased risk of heart failure (HF), but evidence was inconclusive. We aimed to determine the effects of DPP-4 inhibitors on risk of HF. METHODS: An extensive search in PubMed, EMBASE, CINAHL, IPA, Cochrane, ClinicalTrial.gov and the manufacturers' websites for randomized controlled trials (RCT) of all DPP-4 inhibitors was performed up to June 2015. All RCTs comparing DPP-4 inhibitors to any comparators with minimum follow-up of 12 weeks were included. The primary outcome was the occurrence of HF. RESULTS: A total of 54 studies with 74,737 participants were included for analysis. Overall, DPP-4 inhibitors were not associated with an increased risk of HF compared to comparators (relative risk (RR) 1.106; 95% CI 0.995-1.228; p=0.062). When analyzed individually, saxagliptin was significantly associated with the increased risk of HF (RR 1.215; 95% CI, 1.028-1.437; p=0.022), while others were not. Age >= 6 5 years, diabetes duration of >= 10 years and BMI >= 30 kg/m(2) were associated with an increased risk of HF among patients using saxagliptin. CONCLUSIONS: Our meta-analysis suggested a differential effect of each DPP-4 inhibitor on the risk of HF. Use of saxagliptin significantly increases the risk of HF by 21% especially among patients with high CV risk while no signals were detected with other agents. This information should be taken into consideration when prescribing DDP-4 inhibitors. PMID- 26991556 TI - Natriuretic peptides, nitrite/nitrate and superoxide dismutase have additional value on top of the GRACE score in prediction of one-year mortality and rehospitalisation for heart failure in STEMI patients - Multiple biomarkers prospective cohort study. AB - BACKGROUND: Blood-based biomarkers have a prognostic value in patients with myocardial infarction. The aim of our prospective observational cohort study was to evaluate the prognostic value of biomarkers of different pathophysiological pathways for the occurrence of 1-year all-cause mortality and hospitalisation due to acute heart failure. METHODS AND RESULTS: In 593 patients with ST-segment elevation MI (STEMI) treated by primary PCI, biomarkers were evaluated at 24h after MI onset. A minimum of three-year follow-up was achieved in all patients. The combination of 1-year all-cause mortality and hospitalisation due to heart failure was the primary endpoint. A cohort for validation of our combined GRACE natriuretic peptide (NP) score included 667 STEMI patients. The primary endpoint was reached in 9.3% of patients. Among 21 biomarkers, only B-type natriuretic peptide (BNP), NT-proBNP, superoxide dismutase and nitrite/nitrate, added to clinical GRACE score led to a significant increase in the area under the curve of C statistics, in comparison to GRACE alone (tested by Delong's test). Continuous net reclassification improvement and integrated discrimination index demonstrated an improved reclassification and discrimination of the GRACE model for SOD, BNP and NT-proBNP, and improved reclassification for nitrite/nitrate. Consistent results for this new combined prognostic model GRACE-NP were found also for a validation cohort. CONCLUSIONS: The levels of NP have an additional value to the prognostic properties of the GRACE score for the prediction of the combined endpoint of one-year mortality or hospitalisation for AHF. Nitrite/nitrate and SOD are strong prognostic factors, even on top of the GRACE score. PMID- 26991557 TI - Halogenase-Inspired Oxidative Chlorination Using Flavin Photocatalysis. AB - Chlorine gas or electropositive chlorine reagents are used to prepare chlorinated aromatic compounds, which are found in pharmaceuticals, agrochemicals, and polymers, and serve as synthetic precursors for metal-catalyzed cross-couplings. Nature chlorinates with chloride anions, FAD-dependent halogenases, and O2 as the oxidant. A photocatalytic oxidative chlorination is described based on the organic dye riboflavin tetraacetate mimicking the enzymatic process. The chemical process allows within the suitable arene redox potential window a broader substrate scope compared to the specific activation in the enzymatic binding pocket. PMID- 26991558 TI - MGL2/YMR210w encodes a monoacylglycerol lipase in Saccharomyces cerevisiae. AB - In silico analysis of the uncharacterized open reading frame YMR210w in Saccharomyces cerevisiae revealed that it possesses both an alpha/beta hydrolase domain (ABHD) and a typical lipase (GXSXG) motif. The purified protein displayed monoacylglycerol (MAG) lipase activity and preferred palmitoyl-MAG. Overexpression of YMR210w in the known MAG lipase mutant yju3Delta clearly revealed that the protein had MAG lipase activity, hence we named the ORF MGL2. Overexpression of YMR210w decreased the cellular triacylglycerol levels. Analysis of the overexpressed strains showed reduction in the lipid droplets number and size. Phenotype studies revealed that the double deletion yju3Deltamgl2Delta displayed a growth defect that was partially restored by MGL2 overexpression. PMID- 26991560 TI - Make Room on Your Shelves. PMID- 26991562 TI - Injury Trends in Major League Baseball Over 18 Seasons: 1998-2015. AB - Since Major League Baseball (MLB) expanded to its current size of 30 teams in 1998, a comprehensive and longitudinal study of injury trends has not been performed. The purpose of this work is to report the epidemiology of injuries in MLB over that time utilizing disabled list (DL) data. Additionally, we sought to determine the financial impact of these injuries for MLB teams. During this analysis, we focused special attention on injuries of the medial ulnar collateral ligament (MUCL) and conducted a comprehensive review of all MUCL reconstructions ever performed on MLB players. Over the study period, there were a total of 8357 DL designations (mean of 464 annually). Players lost a total of 460,432 days (25,186 days annually) due to injury. Both the number of DL assignments and number of DL days increased from year to year (P < .001 and P = .003, respectively). Average length of DL assignments remained steady over time at 55.1 days (P = .647). Although shoulder injuries decreased (P = .023), this was met with a reciprocal increase in elbow injuries (P = .015). The average annual cost of designating players to the DL was $423,267,634 and a total of $7,618,817,407 was spent over the entire 18 seasons. Regarding MUCL injuries, a total of 400 MUCL reconstructions were performed in MLB players between 1974 and 2015, and the mean time to return to MLB competition was 17.1 months. The annual incidence of MUCL reconstructions increased dramatically from year to year (P < .001) and nearly one-third (n = 131, 32.8%) of all procedures performed over the 42-year period occurred in the last 5 years (2011 to 2015). In summary, overall injury rates and DL assignments continue to rise. Although shoulder injuries are declining, this improvement is countered by increasing elbow injuries, and these injuries continue to represent a significant source of lost revenue. PMID- 26991561 TI - Throwing, the Shoulder, and Human Evolution. AB - Throwing with accuracy and speed is a skill unique to humans. Throwing has many advantages and the ability to throw has likely been promoted through natural selection in the evolution of humans. There are many unsolved questions regarding the anatomy of the human shoulder. The purpose of this article is to review many of these mysteries and propose that the answer to these questions can be understood if one views the shoulder as a joint that has evolved to throw. PMID- 26991559 TI - The effect of inflammation and its reduction on brain plasticity in multiple sclerosis: MRI evidence. AB - Brain plasticity is the basis for systems-level functional reorganization that promotes recovery in multiple sclerosis (MS). As inflammation interferes with plasticity, its pharmacological modulation may restore plasticity by promoting desired patterns of functional reorganization. Here, we tested the hypothesis that brain plasticity probed by a visuomotor adaptation task is impaired with MS inflammation and that pharmacological reduction of inflammation facilitates its restoration. MS patients were assessed twice before (sessions 1 and 2) and once after (session 3) the beginning of Interferon beta (IFN beta), using behavioural and structural MRI measures. During each session, 2 functional MRI runs of a visuomotor task, separated by 25-minutes of task practice, were performed. Within session between-run change in task-related functional signal was our imaging marker of plasticity. During session 1, patients were compared with healthy controls. Comparison of patients' sessions 2 and 3 tested the effect of reduced inflammation on our imaging marker of plasticity. The proportion of patients with gadolinium-enhancing lesions reduced significantly during IFN beta. In session 1, patients demonstrated a greater between-run difference in functional MRI activity of secondary visual areas and cerebellum than controls. This abnormally large practice-induced signal change in visual areas, and in functionally connected posterior parietal and motor cortices, was reduced in patients in session 3 compared with 2. Our results suggest that MS inflammation alters short-term plasticity underlying motor practice. Reduction of inflammation with IFN beta is associated with a restoration of this plasticity, suggesting that modulation of inflammation may enhance recovery-oriented strategies that rely on patients' brain plasticity. Hum Brain Mapp 37:2431-2445, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991563 TI - Ulnar Collateral Ligament Repair: An Old Idea With a New Wrinkle. AB - At our practice, we have successfully treated thousands of overhead athletes with the modified Jobe technique of ulnar collateral ligament (UCL) repair. We used this technique regardless of the amount and location of the pathology encountered at the time of surgery. We asked whether the availability of modern anchor and suture technology, vast clinical experience with these injuries and their outcomes, and even biologic additives could be applied to some of these patients to achieve an equal or superior outcome in less time. This led us to create a construct that could be used to not only repair the torn native UCL tissue to bone, but also span the anatomic native ligament from its origin to its insertion. This construct includes an ultra-strong collagen coated tape attached at the anatomic insertions of the ligament using two 3.5-mm nonabsorbable PEEK corkscrew anchors and a suture through the eyelet of one of the anchors. PMID- 26991564 TI - Arthroscopic Management of Full-Thickness Rotator Cuff Tears in Major League Baseball Pitchers: The Lateralized Footprint Repair Technique. AB - Clinical outcomes of surgical management of full-thickness rotator cuff tears in professional baseball players have been uniformly poor. We conducted a study to investigate return-to-play data and functional performance using a novel arthroscopic repair technique. We hypothesized that arthroscopic rotator cuff repair would result in a high rate of return to professional pitching and favorable functional outcomes. We identified 6 consecutive Major League Baseball (MLB) pitchers who underwent surgical repair of full-thickness rotator cuff injuries using the lateralized footprint repair technique. At most recent follow up, patients were evaluated to determine their ability to return to athletic activity. Functional outcomes were also assessed using player performance statistics. By mean follow-up of 66.7 months (range, 23.2-94.6 months), 5 (83%) of the 6 pitchers had returned to their preinjury level of competition for at least 1 full season. Despite the high rate of return to MLB play, few pitchers resumed pitching productivity at their preoperative level; mean number of innings pitched decreased from 1806.5 to 183.7. A slight performance reduction was also found in a comparison of preoperative and postoperative pitching statistics. Of note, the return rate was higher for players over age 30 years than for those under 30 years. Overhead athletes require a delicate balance of shoulder mobility and stability to meet functional demands. Anatomical adaptations at the glenohumeral joint should be considered when performing rotator cuff repair in these patients in order to preserve peak functional performance. This novel repair technique affords a high rate of return to MLB play, though elite overhead throwers should be counseled that pitching productivity might decrease after surgery. PMID- 26991565 TI - Hand Blisters in Major League Baseball Pitchers: Current Concepts and Management. AB - Friction blisters are a common sequela of many athletic activities. Their significance can range from minor annoyance to major performance disruptions. The latter is particularly true in baseball pitchers, who sustain repeated trauma between the baseball seams and the fingers of the pitching hand, predominately at the tips of the index and long fingers. Since 2010, 6 Major League Baseball (MLB) players accounted for 7 stints on the disabled list (DL) due to blisters. These injuries resulted in a total of 151 days spent on the DL. Since 2012, 8 minor league players spent time on the DL due to blisters. Moreover, there have been several documented and publicized instances of professional baseball pitchers suffering blisters that did not require placement on the DL but did result in injury time and missed starts. The purpose of this article is to review the etiology and pathophysiology of friction blisters with particular reference to baseball pitchers; provide an overview of past and current prevention methods; and discuss our experience in treating friction blisters in MLB pitchers. PMID- 26991566 TI - Epidemiology, Treatment, and Prevention of Lumbar Spine Injuries in Major League Baseball Players. AB - In recent years, increased attention has been paid to injuries occurring in Major League Baseball (MLB) players. Although most of the current orthopedic literature regarding baseball injuries pertains to the shoulder and elbow, lumbar spine injuries are another common reason for time out of play. Back and core injuries may represent as many as 12% of all injuries that result in time out of play from MLB. This high rate of injury is likely related to the critical role that the spine plays in every major baseball-related movement. Linking the upper extremities to the hips and lower extremities, a healthy, strong, and stable spine and core is a prerequisite for performance in all levels of baseball. It has been well documented that baseball players with poor spinal control and stabilization are at increased risk for future injury. Common etiologies of lumbar injuries include stress fractures, muscle injury, annular tears with or without disc herniation, facet joint pain, sacroiliac joint pain, and stenosis. This review discusses the epidemiology of spinal injuries in baseball. Special attention is paid to the role of the spine in baseball-related activities, common injuries, tips for making the correct diagnosis, treatment options, outcomes, rehabilitation, and injury prevention. PMID- 26991567 TI - Valgus Extension Overload in Baseball Players. AB - Repetitive throwing, such as in baseball pitching, applies massive stress on the elbow. This can often lead to a predictable constellation of elbow injuries, such as valgus extension overload syndrome (VEO). The following review of VEO provides an understanding of relevant anatomy, explanation of pathomechanics, key aspects to clinical evaluation, effective treatment options, and indications for surgery. In addition, we provide the senior author's (CSA) preferred arthroscopic technique for cases of VEO refractory to conservative management. PMID- 26991568 TI - Predicting and Preventing Injury in Major League Baseball. AB - Major League Baseball (MLB) players are at significant risk for both chronic, repetitive overuse injuries as well as acute traumatic injuries. Pitchers have been shown to be at higher risk for sustaining injuries, especially upper extremity injuries, than position players. The past several MLB seasons have seen a dramatic rise in the number of ulnar collateral ligament reconstructions performed in MLB pitchers. Several recent prospective studies have identified risk factors for injuries to both the shoulder and elbow in MLB pitchers. These risk factors include a lack of external rotation, a lack of total rotation, and a lack of flexion in the throwing arm. Thus far, no study has demonstrated a correlation between cumulative work (number of games pitched, total pitches thrown, total innings pitched, innings pitched per game, and pitches thrown per game) and injuries in MLB pitchers, despite several studies showing this correlation in youth pitchers. Although many risk factors have been translated into guidelines for prevention, no study has been conducted to determine whether adherence to these guidelines effectively prevents injuries. Further studies are necessary to define exactly how injuries in MLB players can be prevented. PMID- 26991569 TI - Interval Throwing and Hitting Programs in Baseball: Biomechanics and Rehabilitation. AB - Baseball injuries from throwing and hitting generally occur as a consequence of the repetitive and high-energy motions inherent to the sport. Biomechanical studies have contributed to understanding the pathomechanics leading to injury and to the development of rehabilitation programs. Interval-based throwing and hitting programs are designed to return an athlete to competition through a gradual progression of sport-specific exercises. Proper warm-up and strict adherence to the program allows the athlete to return as quickly and safely as possible. PMID- 26991570 TI - Latissimus Dorsi and Teres Major Injuries in Major League Baseball Pitchers: A Systematic Review. AB - Injuries to the upper extremity in baseball pitchers are not uncommon, with extensive literature on shoulder and elbow pathology. However, there is minimal literature on isolated teres major (TM) and latissimus dorsi (LD) injuries. As a result, there is no consensus on an optimal treatment method. An extensive Medline search on studies focusing on the treatment of isolated LD and TM injuries in professional baseball pitchers was performed to explore this topic. Of the 20 retrieved articles, 5 met our inclusion criteria. There were a total of 29 patients who underwent conservative treatment and 1 who underwent surgical treatment. The average time required to return to pitching was 99.8 days in the conservative group and 140 days in the surgically treated group. Five patients in the conservative group suffered from complications and/or setbacks during their treatment and rehabilitation. The lone surgical patient suffered no complications, returned to preinjury form, and was elected an all-star the following year. The goal of this review is to provide a concise summary of the current literature in order to assist physicians when discussing treatment options with their patients. PMID- 26991571 TI - The Epidemiology of Hip and Groin Injuries in Professional Baseball Players. AB - Injuries of the hip and groin among professional baseball players can result in a significant number of disabled list days. The epidemiology of these injuries has not been delineated. The purpose of this study is to describe the incidence, mechanism, type, and rehabilitation course of hip and groin injuries among Major League Baseball (MLB) and Minor League Baseball (MiLB) players. The MLB injury database for hip and groin injuries from 2011-2014 was analyzed. Occurrence of injuries was assessed based on level of play, field location, activity during which the injury occurred, mechanism of injury, and days missed. The treatment was recorded as nonoperative or surgical. The subsequent rehabilitation and return to play were recorded. Chi-square tests were used to test the hypothesis of equal proportions between the various categories of hip and groin characteristics. From 2011-2014, 1823 hip and groin injuries occurred among MLB and MiLB players, which accounted for approximately 5% of all injuries. Of these, 1514 (83%) occurred among MiLB players and 309 (17%) among MLB players; 96% of injuries were extra-articular. Among all players, a noncontact mechanism during defensive fielding was the most common activity causing injury (74%), and infielders experienced the most hip and groin injuries (34%). The majority of extra-articular injuries were treated nonoperatively (96.2%), resulting in an average of 12 days missed. Intra-articular pathology more commonly required surgery, and resulted in an average of 123 days missed. Hip and groin injuries can be debilitating and result in a significant number of days missed. Intra articular pathology and athletic pubalgia were usually treated surgically, while the majority of extra-articular hip injuries were treated successfully with nonoperative modalities. Correct diagnosis and appropriate treatment can lead to a high rate of return to play for professional baseball players with injuries to the hip and groin. PMID- 26991572 TI - A Guide to Ultrasound of the Shoulder, Part 1: Coding and Reimbursement. AB - Ultrasound is an inexpensive, easy, mobile, dynamic study that has many advantages over other imaging modalities. Several studies have shown the need for ultrasound during procedures, with significantly improved outcomes and patient satisfaction. Other studies have also shown that ultrasound has medical and economic advantages over magnetic resonance imaging. With the increased use of ultrasound in the office, operating room, and during athletic competitions, the need for accurate coding is essential. Reimbursement is viable for both radiologists and non-radiologists. In the coming year, "appropriate use criteria" will be introduced and implemented. Physicians need to be prepared and informed of all the necessary requirements and coming changes regarding the use and billing of ultrasound procedures. PMID- 26991573 TI - Tibialis Posterior Tendon Entrapment Within Posterior Malleolar Fracture Fragment. AB - Management of posterior malleolus fractures continues to be controversial, with respect to both need for fixation and fixation methods. Fixation methods include an open posterior approach to the ankle as well as percutaneous reduction and fixation with or without arthroscopy for visualization of the articular surface. Plain radiographs are unreliable in identifying fracture pattern and intraoperative reduction, making arthroscopy a valuable adjunct to posterior malleolus fracture management. In this article, we report a case of tibialis posterior tendon entrapment within a posterior malleolus fracture, as identified by arthroscopy and managed with open reduction. Tibialis posterior tendon entrapment within a posterior malleolus has not been previously reported. Ankle arthroscopy for posterior malleolus fractures provides an opportunity to identify soft-tissue or tendinous entrapment, articular surface reduction, and articular cartilage injuries unlikely to be identified with fluoroscopy alone and should be considered in reduction and fixation of posterior malleolus fractures. PMID- 26991574 TI - Extreme Postinjection Flare in Response to Intra-Articular Triamcinolone Acetonide (Kenalog). AB - As intra-articular corticosteroid injections (CSIs) are a common treatment for osteoarthritis, physicians must well understand their potential side effects. Postinjection flares are an acute side effect of intra-articular CSIs, with symptoms ranging from mild joint effusion to disabling pain. The present case involved a severe postinjection flare that occurred after the patient, a 56-year old woman with moderate osteoarthritis in the left knee, received 2 mL of 1% lidocaine and 2 mL (40 mg) of triamcinolone acetonide (Kenalog). Two hours after injection, she experienced swelling and intense pain in the knee and was unable to ambulate. The knee was aspirated with a return of 25 mL of "butterscotch" colored fluid. This case is novel in that its acuity of onset, severity of symptoms, and synovial fluid analysis mimicked septic arthritis, which was ultimately ruled out with negative cultures and confirmation of triamcinolone acetonide crystals in the synovial aspirate, viewed by polarized light microscopy. Thus, the patient's reaction represents an acute crystal-induced inflammatory response. Although reactions to an intra-articular CSI of this severity are rare, it is important for treating physicians to inform patients of this potential side effect. PMID- 26991575 TI - Optimizing Outcomes of Total Joint Arthroplasty Under the Comprehensive Care for Joint Replacement Model. PMID- 26991576 TI - Technical Errors May Affect Accuracy of Torque Limiter in Locking Plate Osteosynthesis. AB - In locking plate osteosynthesis, proper surgical technique is crucial in reducing potential pitfalls, and use of a torque limiter makes it possible to control insertion torque. We conducted a study of the ways in which different techniques can alter the accuracy of torque limiters. We tested 22 torque limiters (1.5 Nm) for accuracy using hand and power tools under different rotational scenarios: hand power at low and high velocity and drill power at low and high velocity. We recorded the maximum torque reached after each torque-limiting event. Use of torque limiters under hand power at low velocity and high velocity resulted in significantly (P < .0001) different mean (SD) measurements: 1.49 (0.15) Nm and 3.73 (0.79) Nm. Use under drill power at controlled low velocity and at high velocity also resulted in significantly (P < .0001) different mean (SD) measurements: 1.47 (0.14) Nm and 5.37 (0.90) Nm. Maximum single measurement obtained was 9.0 Nm using drill power at high velocity. Locking screw insertion with improper technique may result in higher than expected torque and subsequent complications. For torque limiters, the most reliable technique involves hand power at slow velocity or drill power with careful control of insertion speed until 1 torque-limiting event occurs. PMID- 26991577 TI - On Track to Professorship? A Bibliometric Analysis of Early Scholarly Output. AB - Academic productivity, demonstrated by a record of scholarly publication, is the main criterion for academic promotion. Nevertheless, there are no data on early career productivity milestones to guide young faculty members aspiring to attain professor status. We performed a bibliometric analysis to determine the number of scholarly papers published by current professors of orthopedic surgery within 5 years after their having acquired American Board of Orthopaedic Surgery certification (termed early scholarly output). Median early scholarly output for all professors (N = 108) was 11 publications. We found medians of 5 first-author and 2 last-author publications, and 4 publications in Clinical Orthopaedics and Related Research or Journal of Bone and Joint Surgery. Median number of papers cited at least 50 times by year 5 was 2. The median number of total citations was 29.5, and median Hirsch index (h-index) was 3. Faculty who were clinical professors published fewer papers and acquired fewer citations than faculty who were promoted but did have the clinical descriptor. Professors certified after 1995 were more productive than those certified before 1990. This descriptive study provided benchmark data on early scholarly productivity of current professors of orthopedic surgery and demonstrated this benchmark has risen in more recent years. PMID- 26991578 TI - Sports Medicine Fellowship: What Should I Be Looking For? PMID- 26991579 TI - Partial Flexor Tendon Laceration Assessment: Interobserver and Intraobserver Reliability. AB - Accurate assessment of partial-thickness flexor tendon lacerations in the hand is difficult owing to the subjectivity of evaluation. In this study, we created 12 partial-thickness flexor tendon lacerations in a cadaveric hand, evaluated the accuracy of 6 orthopedic residents and 4 fellowship-trained hand surgeons in estimating the percentage thickness of each laceration, and assessed the groups' interobserver and intraobserver agreement. The 10 participants estimated each laceration independently and on 2 separate occasions and indicated whether they would repair it. The actual thickness of each laceration was calculated from measurements made with a pair of digital microcalipers. Overall estimates differed significantly from calibrated measurements. Estimates grouped by residents and fellowship-trained hand surgeons also differed significantly. Third year residents were the most accurate residents, and fellowship-trained hand surgeons were more accurate than residents. Overall interobserver agreement was poor for both readings. There was moderate overall intraobserver agreement. Fellowship-trained hand surgeons and first-year residents had the highest intraobserver agreement. These results highlight the difficulty in accurately assessing flexor tendon lacerations. Accuracy appears not to improve with surgeon experience. PMID- 26991580 TI - Progressive Cardiomyopathy in a Patient With Elevated Cobalt Ion Levels and Bilateral Metal-on-Metal Hip Arthroplasties. AB - Systemic cobalt toxicity is a rare complication after metal-on-metal (MOM) total hip arthroplasty. Here we present a case of progressive cardiomyopathy, as evidenced by biopsy and cardiac magnetic resonance imaging (MRI), in a patient with bilateral MOM total hip arthroplasties. To our knowledge, it is one of the first cases in which cardiomyopathy resulting from systemic cobalt disease has been shown on MRI. While there is no guideline to unequivocally diagnose cobalt cardiomyopathy, the constellation of findings, including pathologic, biologic, blood levels, imaging, and surgical, all uniformly indicate a unifying diagnosis. The lack of improvement after removal of the prosthetic device supports a diagnosis of permanent myocardial damage, which is consistent with cardiomyopathy of advanced toxic etiology. PMID- 26991581 TI - Evaluation of Internet Information About Rotator Cuff Repair. AB - The content and quality of Internet websites are not governed or regulated. Therefore, patients who consult the Internet may receive outdated or incorrect medical information. Researchers have analyzed the quality of web information about various orthopedic surgeries, but no such analysis has been performed on websites covering rotator cuff repair. We conducted a study to evaluate and analyze rotator cuff repair information available to the general public through the Internet; to assess changes in the quality of information over time; to determine if sites sponsored by academic institutions offered higher-quality information; and to assess whether the readability of the material varied according to DISCERN scores. Two Internet searches were conducted, in 2011 and 2014. The 3 most commonly used search engines were used to search for rotator cuff repair. The first 50 websites from each search engine were evaluated for authorship and content. The DISCERN instrument was used to analyze the quality of each website's health information. The 2011 search revealed 21% of websites were associated with an academic institution, 38% were authored by a hospital or physician group, and 11.5% were industry-sponsored. The 2014 search revealed a similar distribution of contributors. The highest DISCERN scores were given to academic institution websites (51.6) and public education websites (49). There was no correlation between readability and DISCERN scores. Websites associated with academic institutions produced the highest-quality medical information. Over the past few years, authorship and content have changed little with respect to Internet information about rotator cuff repair. PMID- 26991582 TI - Treating Tibia Fractures With Far Cortical Locking Implants. AB - Compared with conventional plating, the relatively new technology of far cortical locking (FCL) allows for more flexible fixation. Increased flexibility of FCL constructs is thought to better stimulate secondary osteosynthesis and lead to improved healing for certain fracture patterns. We conducted a study to compare healing rates and complications of tibial fractures treated with FCL or standard plating techniques. Twenty-two patients with fractures of the tibia (Orthopaedic Trauma Association 41ABC, 42C, 43C) were included in the study. Twelve tibia fractures were treated with FCL and 10 with standard plating (locking or nonlocking). Mean follow-up was 47 weeks in the FCL group and 41 weeks in the control group. The fracture healing rate was 92% in the FCL group and 100% in the control group (difference not statistically significant). Of note, there were 2 open fractures in the FCL group and 0 in the control group. The groups had similar complication rates. Our study data suggest FCL implants are not inferior to conventional plating techniques. Given that FCL-treated fractures tended to be more complex, the groups' similar fracture healing rates may indicate improved fracture healing with FCL technology, but this possibility requires further investigation. PMID- 26991583 TI - 14-Year-Old Boy With Mild Antecedent Neck Pain in Setting of Acute Trauma: A Rare Case of Benign Fibrous Histiocytoma of the Spine. AB - A 14-year-old boy presented to the emergency department with neck pain after a football accident. Imaging revealed a discrete, expansile, lytic, radiolucent mass extending anterior from the left C2 vertebral body. The differential diagnosis for this mass is broad and includes both benign and malignant lesions. A thorough history and physical examination, along with selective imaging and a tissue sample, are essential in making the correct diagnosis. We report a case of benign fibrous histiocytoma (BFH) in the cervical spine of a pediatric patient, present the diagnostic dilemma involved in diagnosing BFH, and review the literature to compare the characteristics of BFH with those of other benign bone lesions. To our knowledge, this is only the second reported case of BFH in the cervical spine of a pediatric patient. PMID- 26991584 TI - Epidemiology and Impact of Knee Injuries in Major and Minor League Baseball Players. AB - Few studies have explored the frequency and impact of lower extremity injuries, such as those to the knee, among professional baseball players. The purpose of this study was to detail the epidemiology of knee injuries in Major League Baseball (MLB) and Minor League Baseball (MiLB) players during the 2011-2014 seasons. It was hypothesized that knee injuries are a common occurrence in these athletes, and represent a significant source of time away from play. The MLB Health and Injury Tracking System database was searched to identify all patients diagnosed with knee injuries during the 2011-2014 seasons. All injuries that occurred during the preseason, regular season, and postseason that resulted in time away from play were included. Injury data analyzed included total number of knee injuries, specific diagnoses, injury mechanisms, locations, player positions, and time lost. Descriptive statistics were conducted and injury rates per athlete-exposures were calculated. During the 2011-2014 seasons, a total of 2171 knee injuries occurred in MLB and MiLB players, representing 6.5% of all injuries in professional baseball. The knee injury rate across both the MLB and MiLB was 1.2 per 1000 athlete-exposures. The mean number of days missed per injury across both leagues was 16.2 with a total of 30,449 days of missed play amongst all athletes over the 4 seasons. Injuries to the knee were the fifth most common cause of missed time in all of baseball, and the fourth most common reason for missed games in the MLB alone. Approximately 12% of all injuries required surgical intervention. The most common mechanism of injury was noncontact (44%), and base runners were injured more frequently than any other position (24%). The infield (30%) and home plate (23%) were the most common locations in which injuries occurred. These data can be utilized for targeted injury prevention initiatives. PMID- 26991585 TI - Neurocognitive Deficits and Cerebral Desaturation During Shoulder Arthroscopy With Patient in Beach-Chair Position: A Review of the Current Literature. AB - Arthroscopic shoulder surgery with the patient in the beach-chair position (BCP) has been associated with neurocognitive complications caused by cerebral ischemia. We reviewed the current literature for the incidence of postoperative neurocognitive deficits, number of reported neurocognitive complications, and incidence of intraoperative cerebral desaturation events in patients who underwent arthroscopic shoulder surgery in the BCP. Among 10 studies with a composite enrollment of 24,701 patients, there was only 1 case of a postoperative neurocognitive deficit (overall incidence, 0.004%). Four case reports (not included in the 10 studies) described 6 patients with a catastrophic neurocognitive complication after shoulder surgery in the BCP. Incidence of reported intraoperative cerebral desaturation events varied significantly (0% 100%; mean, 41.1%). Neurocognitive complications have been reported in patients who had arthroscopic shoulder surgery in the BCP. Intraoperative monitoring of cerebral perfusion, alternatives to general anesthesia, and prudent use of intraoperative blood pressure control may improve patient safety. PMID- 26991586 TI - Operative Versus Nonoperative Treatment of Jones Fractures: A Decision Analysis Model. AB - Optimal management of metadiaphyseal fifth metatarsal fractures (Jones fractures) remains controversial. Decision analysis can optimize clinical decision-making based on available evidence and patient preferences. We conducted a study to establish the determinants of decision-making and to determine the optimal treatment strategy for Jones fractures using a decision analysis model. Probabilities for potential outcomes of operative and nonoperative treatment of Jones fractures were determined from a review of the literature. Patient preferences for outcomes were obtained by questionnaire completed by 32 healthy adults with no history of foot fracture. Derived values were used in the model as a measure of utility. A decision tree was constructed, and fold-back and sensitivity analyses were performed to determine optimal treatment. Nonoperative treatment was associated with a value of 7.74, and operative treatment with an intramedullary screw was associated with a value of 7.88 given the outcome probabilities and utilities studied, making operative treatment the optimal strategy. When parameters were varied, nonoperative treatment was favored when the likelihood of healing with nonoperative treatment rose above 82% and when the probability of healing after surgery fell below 92%. In this decision analysis model, operative fixation is the preferred management strategy for Jones fractures. PMID- 26991587 TI - Clinical Outcomes of Minimally Invasive Versus Open TLIF: A Propensity-Matched Cohort Study. AB - In this study, we compare intermediate-term outcomes in minimally invasive surgical transforaminal lumbar interbody fusion (MIS TLIF) to open TLIF. Sixty four patients who underwent 1- to 2-level MIS TLIF with baseline, 1-, and 2-year outcome measures were identified. These were propensity-matched to a cohort of open TLIF patients based on age, body mass index, sex, smoking status, workers' compensation status, and preoperative outcome measures. At 1 year, both groups had similar improvements in pain and Short-Form 36 (SF-36) Physical Composite Summary (PCS), but the MIS TLIF group had a statistically significantly greater improvement in Oswestry Disability Index (ODI) compared with the open TLIF group. At 2 years, the MIS TLIF group had a statistically significantly greater improvement in pain and ODI compared with the open TLIF group, but no statistically significant difference in SF-36 PCS. Both MIS TLIF and open TLIF lead to significant improvements in clinical outcomes. At 1 year after surgery, MIS TLIF patients had greater improvements in ODI, and at 2 years after surgery, they had greater improvements in pain and ODI. This study showed that the perioperative advantages of MIS TLIF, such as less muscle dissection and faster recovery, continue to be beneficial 1 to 2 years after surgery. PMID- 26991588 TI - In Vivo Measurement of Rotator Cuff Tear Tension: Medial Versus Lateral Footprint Position. AB - We conducted a study to evaluate in vivo tension applied to the rotator cuff tendon positioned at the medial versus lateral footprint during arthroscopic rotator cuff repair. We evaluated 20 consecutive patients who underwent arthroscopic rotator cuff repair. During repair, a grasper was inserted through a lateral portal, and a digital weigh scale was attached. The tendon was grasped and translated to the medial footprint, and tension recorded. After a relaxation period, the tendon edge was translated to the lateral footprint, and tension recorded. Mean (SD) tension was 0.41 (0.33) pound when tendons were positioned at the medial footprint and 2.21 (1.20) pounds when they were positioned at the lateral footprint, representing a 5.4-fold difference (P < .0001). For smaller tears (<= 20 mm anterior-posterior), 7.6 times less tension was applied to the tendons when pulled to the medial versus lateral footprint. For larger tears, 4.1 times less tension was applied to the tendons when pulled to the medial versus lateral footprint. This study demonstrated a significant, 5.4-fold increase in tension when the tendon edge was reduced to the lateral as opposed to the medial footprint in vivo. PMID- 26991589 TI - Shoulder Instability Management: A Survey of the American Shoulder and Elbow Surgeons. AB - Despite an abundance of peer-reviewed literature, there is wide surgical practice variability for symptomatic shoulder instability. In this study, we identified consensus trends among specialists in glenohumeral instability. A survey was distributed to 417 members of the American Shoulder and Elbow Surgeons (ASES). Surveys consisted of 3 sections: surgeon demographics, presentation of 5 case scenarios, and instability management. Consensus responses were defined as more than 50% of participants giving a single response with more than 2 answer choices or more than 67% of participants giving a single response when 2 answer choices were available. We assessed 125 completed surveys (29.9% response rate); 68% of questions reached a consensus answer. Arthroscopic Bankart repair was the preferred technique for young noncontact (82%), young contact (57%), and weekend warrior athletes (60%). In the setting of glenoid bone loss, 72.8% recommended the Latarjet procedure. Remplissage was the procedure of choice (60%) for engaging Hill-Sachs lesions. The ASES members favored arthroscopic Bankart repair in the absence of glenoid bone loss or engaging Hill-Sachs lesion, regardless of age (20 to 35 years) or nature of sport (contact vs noncontact). For Hills-Sachs lesions, consensus response favored remplissage, while a Latarjet procedure was advocated for glenoid lesions. PMID- 26991590 TI - Are Hook Plates Advantageous Compared to Antiglide Plates for Vertical Shear Malleolar Fractures? AB - This study was designed to evaluate the biomechanical properties of a hook plate (HP) vs an antiglide (AG) plate for supination-adduction (SAD)-ankle fractures. Identical polyurethane tibial models were obtained and vertical fractures were created. The fractures were stabilized with 1 of the following: one-third tubular plate in an AG fashion with 2 screws proximal to the fracture; an AG plate with an additional screw perpendicular to the vertical shear fragment (MAG), or an HP. Ten models were randomly assigned to each of the 3 groups. The constructs were tested in offset-axial loading and were evaluated for construct stiffness and load-to-failure. The MAG construct yielded better stiffness compared with the AG plate (P < .05) and the HP (P < .05). The plate stiffness of the HP construct compared with the AG was not significant (P = .350). In regards to load-to failure, the difference between MAG and AG was 638 N, and MAG and HP was 530 N (both P < .05). The HP had a load-to-failure that was, on average, 108 N more than the AG but was not significant (P = .063). A one-third tubular plate in the MAG fashion provided a stable, strong construct for fixation of vertical shear medial malleolus fractures. PMID- 26991591 TI - Long-Term Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Polypoidal Choroidal Vasculopathy. AB - PURPOSE: To investigate a clinical outcome after more than 4 years for polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (VEGF) therapy and to investigate the factors predictive of long-term visual outcomes. METHODS: This retrospective study included 31 eyes, with PCV treated with anti-VEGF therapy (either ranibizumab or bevacizumab, or both), and were followed up for 4 years or longer. The best-corrected visual acuity (BCVA) at baseline was compared with that measured at 3 months and at the final follow-up. Factors associated with final visual acuity were also analyzed. RESULTS: The mean follow-up period was 53.0 +/- 4.3 months. During the follow-up period, the patients were treated with an average of 8.8 +/- 3.0 intravitreal anti-VEGF injections. BCVA at diagnosis at 12, 24, and 36 months, and at final follow-up was 0.52 +/- 0.35, 0.46 +/- 0.36, 0.57 +/- 0.45, 0.76 +/- 0.56, and 0.83 +/- 0.60, respectively. When compared to the baseline value, the BCVA was significantly improved at 3 months (P = 0.006), whereas the BCVA at final follow up was significantly decreased compared to the baseline value (P = 0.018). Among the included eyes, 48.4% experienced deterioration of visual acuity and 51.6% showed stable vision. BCVA at 12 months was most strongly associated with visual acuity at final follow-up. CONCLUSIONS: Although the long-term treatment outcome of PCV is generally unfavorable, stable vision can be achieved in approximately half of the patients. Visual acuity at 12 months after the initial treatment is predictive of long-term visual outcomes. PMID- 26991592 TI - Evaluation of patients' sleep by nurses in an ICU. AB - AIMS AND OBJECTIVES: To determine how intensive care unit evaluations of patients' sleep by nurses correspond to polysomnography and if changes in patients' physiologic parameters could be helpful in sleep evaluation. BACKGROUND: The evaluations of patients' sleep by nurses have not corresponded very well with objective sleep recordings, so there is a need for further knowledge in this field. DESIGN: Correlational study of patients' sleep, nurses' sleep evaluations and the sleep-related heart rate and blood pressure changes. METHODS: The standard overnight polysomnography was recorded on 21 patients. Simultaneously, nurses marked into an electronic patient care documentation system all the changes noted in the patients' sleep status. Patients' arterial blood pressure and heart-rate data were automatically saved into the electronic patient care documentation. RESULTS: The evaluations of patients' sleep/wake state by nurses corresponded to polysomnography 68% of the time. A correlation was found between nurses' evaluations and polysomnography recordings only on total sleep time. There was no correlation in the other sleep aspects (sleep latency, amount of awakenings or movements during sleep). Most patients' blood pressures and heart rate varied according to sleep/wake state. There was less variation if the patient had received noradrenalin for blood pressure control. CONCLUSION: The evaluations of patients' sleep/wake state by nurses only correspond to the polysomnography two-thirds of the time. Thus, more sophisticated evaluation methods should be developed to aid nurses in sleep evaluations. Sleep-related changes in blood pressure and heart rate can be seen in intensive care unit patients, so using these parameters as part of the patients' sleep evaluation should be further explored. RELEVANCE TO CLINICAL PRACTICE: The nurses' evaluation practices of intensive care unit patients' sleep need further development. Monitoring the changes in patients' heart rate and blood pressure may aid in evaluating his/her sleep. PMID- 26991595 TI - The role of time and species identities in spatial patterns of species richness and conservation. AB - Many conservation actions are justified on the basis of managing biodiversity. Biodiversity, in terms of species richness, is largely the product of rare species. This is problematic because the intensity of sampling needed to characterize communities and patterns of rarity or to justify the use of surrogates has biased sampling in favor of space over time. However, environmental fluctuations interacting with community dynamics lead to temporal variations in where and when species occur, potentially affecting conservation planning by generating uncertainty about results of species distribution modeling (including range determinations), selection of surrogates for biodiversity, and the proportion of biodiversity composed of rare species. To have confidence in the evidence base for conservation actions, one must consider whether temporal replication is necessary to produce broad inferences. Using approximately 20 years of macrofaunal data from tidal flats in 2 harbors, we explored variation in the identity of rare, common, restricted range, and widespread species over time and space. Over time, rare taxa were more likely to increase in abundance or occurrence than to remain rare or disappear and to exhibit temporal patterns in their occurrence. Space-time congruency in ranges (i.e., spatially widespread taxa were also temporally widespread) was observed only where samples were collected across an environmental gradient. Fifteen percent of the taxa in both harbors changed over time from having spatially restricted ranges to having widespread ranges. Our findings suggest that rare species can provide stability against environmental change, because the majority of species were not random transients, but that selection of biodiversity surrogates requires temporal validation. Rarity needs to be considered both spatially and temporally, as species that occur randomly over time are likely to play a different role in ecosystem functioning than those exhibiting temporal structure (e.g., seasonality). Moreover, temporal structure offers the opportunity to place management and conservation activities within windows of maximum opportunity. PMID- 26991593 TI - Leydig cells contribute to the inhibition of spermatogonial differentiation after irradiation of the rat. AB - Irradiation with 6 Gy produces a complete block of spermatogonial differentiation in LBNF1 rats that would be permanent without treatment. Subsequent suppression of gonadotropins and testosterone (T) restores differentiation to the spermatocyte stage; however, this process requires 6 weeks. We evaluated the role of Leydig cells (LCs) in maintenance of the block in spermatogonial differentiation after exposure to radiation by specifically eliminating functional LCs with ethane dimethane sulfonate (EDS). EDS (but not another alkylating agent), given at 10 weeks after irradiation, induced spermatogonial differentiation in 24% of seminiferous tubules 2 weeks later. However, differentiation became blocked again at 4 weeks as LCs recovered. When EDS was followed by treatment with GnRH antagonist and flutamide, sustained spermatogonial differentiation was induced in >70% of tubules within 2 weeks. When EDS was followed by GnRH antagonist plus exogenous T, which also inhibits LC recovery but restores follicle stimulating hormone (FSH) levels, the spermatogonial differentiation was again rapid but transient. These results confirm that the factors that block spermatogonial differentiation are indirectly regulated by T, and probably FSH, and that adult and possibly immature LCs contribute to the production of such inhibitory factors. We tested whether insulin-like 3 (INSL3), a LC-produced protein whose expression correlated with the block in spermatogonial differentiation, was indeed responsible for the block by injecting synthetic INSL3 into the testes and knocking down its expression in vivo with siRNA. Neither treatment had any effect on spermatogonial differentiation. The Leydig cell products that contribute to the inhibition of spermatogonial differentiation in irradiated rats remain to be elucidated. PMID- 26991594 TI - Cyanidin-3-glucoside and its phenolic acid metabolites attenuate visible light induced retinal degeneration in vivo via activation of Nrf2/HO-1 pathway and NF kappaB suppression. AB - SCOPE: Cyanidin-3-glucoside (C3G) is a major anthocyanin in berries and a potential nutritional supplement for preventing retinal degeneration. However, the protective mechanism of C3G and its metabolites, protocatechuic acid (PCA) and ferulic acid (FA), remain unclear. The molecular mechanisms of C3G and its metabolites against retinal photooxidative damage in vivo are investigated. METHODS AND RESULTS: Pigmented rabbits were orally administered C3G, PCA, and FA (0.11 mmol/kg/day) for 3 weeks. Electroretinography, histological analysis, and TUNEL assay showed that C3G and its metabolites attenuated retinal cell apoptosis. The expression of oxidative stress markers were upregulated after light exposure but attenuated by C3G and FA, which may be attributed to the elevated secretion and expression of heme oxygenase (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2). C3G, PCA, and FA attenuated the secretion or expression of inflammation-related genes; FA suppressed nuclear factor kappa B (NF-kappaB) activation. The treatments attenuated the light-induced changes on certain apoptotic proteins and angiogenesis-related cytokines. CONCLUSION: C3G and FA reduced light-induced retinal oxidative stress by activating the Nrf2/HO-1 antioxidant pathway. FA attenuated the light-induced retinal inflammation by suppressing NF-kappaB activation. C3G and its metabolites attenuated the photooxidation-induced apoptosis and angiogenesis in the retina. PMID- 26991596 TI - Correction: Fabrication of poly-crystalline Si-based Mie resonators via amorphous Si on SiO2 dewetting. AB - Correction for 'Fabrication of poly-crystalline Si-based Mie resonators via amorphous Si on SiO2 dewetting' by Meher Naffouti, et al., Nanoscale, 2016, 8, 2844-2849. PMID- 26991597 TI - Utility of Inferior Vena Cava Filters in Severe Pulmonary Embolism, Catheter directed Therapy in Massive and Submassive Pulmonary Embolism, and HAS-BLED Score to Determine Risk of Major Hemorrhage in Pulmonary Embolism. PMID- 26991598 TI - Serum Levels of Cardiac Markers NT-proANP and NT-proBNP in Brachycephalic bitches at Different Gestational Stages. AB - The aim of this study was to determine serum levels of natriuretic peptide precursors (NT-proANP and NT-proBNP) during pregnancy in brachycephalic bitches. Fifteen healthy multiparous bitches were selected for this prospective study. Serum levels of NT-proANP and NT-proBNP were measured during anoestrous and at 14, 35, 42, 49 and 56 days (2nd, 5th, 6th, 7th and 8th weeks) of pregnancy. Fourteen animals had normal gestations, and one bitch developed single foetus syndrome. The natriuretic peptide levels of this animal were not included in this study; however, it is important to report that its NT-proANP levels were four times greater than those of normal patients. There was no significant difference (p = 0.072) in NT-proBNP levels between anoestrous (0.20 +/- 0.10 ng/ml) and the different pregnancy weeks (0.27 +/- 0.12 ng/ml). There was a positive correlation (p < 0.0001) between NT-proANP and gestational age, and the levels of this marker increased significantly (p < 0.0001) during the 6th (0.26 +/- 0.06 ng/ml), 7th (0.28 +/- 0.04 ng/ml) and 8th weeks (0.29 +/- 0.05 ng/ml) when compared to anoestrous (0.18 +/- 0.02 ng/ml). NT-proANP serum levels are correlated with gestational development and may be indicative of cardiovascular adaptation in canine brachycephalic pregnancy. PMID- 26991599 TI - Exploitation of hazelnut, maize germ and sesame seed aqueous extraction residues in the stabilisation of sesame seed paste (tahini). AB - BACKGROUND: Sesame seed paste is a highly nutritious food product which, upon long-term storage, tends to exhibit undesirable phenomena of oiling-off and particle sedimentation. The ability of rich-in-fibre aqueous extraction powders originating from oleaginous raw materials to enhance the physical stability of sesame paste is investigated in this study. RESULTS: The extraction residues remaining after treating hazelnut, sesame seed or maize germ with aqueous media in order to extract and exploit their oil bodies, were collected, dehydrated and milled into fine powders. The powders were then incorporated at various levels into a commercially available sesame paste product to assess their potential as paste stabilisers against oil separation. The solids from maize germ exhibited the highest stabilising ability followed by the solids from hazelnut. In contrast, the solids originating from the sesame seed were less effective in stabilising the sesame paste. Shear stress-rate of shear measurements of sesame paste incorporating the extraction residue solids were conducted in an attempt to explain the different stabilising behaviour of the three powders. CONCLUSION: The intensity of interactions between the incorporated solids within the sesame paste structure may determine the rheological properties of the blend and hence its stability against oiling-off upon long-term storage. (c) 2016 Society of Chemical Industry. PMID- 26991600 TI - A fluorescent probe for simultaneous discrimination of GSH and Cys/Hcy in human serum samples via distinctly-separated emissions with independent excitations. AB - Biothiols like Cys, Hcy and GSH play important roles in various physiological and pathological processes, and it is still challenging to simultaneously and discriminatively detect GSH and Cys/Hcy due to their similar structures and reaction activities. Hence, it would be highly desirable to design a fluorescent probe for simultaneously discriminating GSH and Cys/Hcy in biological samples with no spectral crosstalk, few interferences and rapid response. Herein, through coupling two fluorophores with biothiol-sensitive linker, we developed a fluorescent probe, which has two biothiol-responsive and distinctly-separated emissions via independent visible-light excitations, for simultaneously discriminating GSH and Cys/Hcy with near-infrared and green emissions. The probe is operable in human serum samples, thus holding promise for diagnostic-related applications. Moreover, the probe shows quite good properties. First, it exhibits a rapid response (within a few minutes) with highly selective and sensitive detection for GSH and Cys/Hcy. Second, it offers an apparent colorimetric and two fluorescence emission signals without spectral crosstalk. Third, it shows low cytotoxicity. Therefore, it would provide a useful method for further elucidating the roles of biothiols as well as for conducting pathological analysis for diseases involving biothiols. PMID- 26991601 TI - A Sensitive and simple macrophage-based electrochemical biosensor for evaluating lipopolysaccharide cytotoxicity of pathogenic bacteria. AB - In this study, a sensitive and simple electrochemical murine macrophage (Ana-1) cell sensor has been developed for early detection of lipopolysaccharides (LPS) to evaluate the toxicity of pathogenic bacteria. Magnetic glassy carbon electrode (MGCE), which possesses excellent reproducibility and regeneration qualities, was modified with a nanocomposite to improve electrochemical signals and enhance the sensitivity. The synthesized magnetic nanoparticles (MNPs) were internalized into murine macrophages, which completed the immobilization of macrophages onto the modified electrode for evaluating the cytotoxicity of LPS by electrochemical impedance spectroscopy (EIS). The MNPs facilitated reusability of the proposed sensor by allowing removal of the magnetic core from the electrode. Our results indicated that LPS caused a marked decrease in electrochemical impedance in a dose-dependent manner in range of 1-5MUg/mL. By SEM, we found that microvilli on the plasma membrane became scarce and the membrane became smooth on cells incubated with LPS, which lessens the absorption of cells to reduce the impedance. And biological assay indicated that EIS patterns were correlated with the calcium concentration in cells, and suggested that [Ca(2+)]i production increased in cells incubated with LPS and its mobilization altered electrochemical signals. Compared with conventional methods, this electrochemical test is inexpensive, highly sensitive, and has a quick response, and thus provides a new avenue for evaluating the cytotoxicity of pathogens. PMID- 26991604 TI - Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure. AB - AIM: More than 7000 male circumcisions are performed in Scandinavia every year. Circumcision is regulated in different ways in Sweden and Denmark and Norway. This study reviewed and described factors associated with complications of circumcision in infant boys in Scandinavia over the last two decades and discussed how these complications could be avoided. METHODS: Data on significant complications following circumcision on boys under the age of one in Scandinavia over the last 20 years were collected. Information was retrieved from testimonies of circumcisers, witnesses, medical records and verdicts. A systematic review was performed of fatal cases in the literature. RESULTS: We found that 32 cases had been reported to the health authorities in the three countries, and we identified a total of 74 complications in these cases. These included four boys with severe bleeding and circulatory shock, which ended in the death of one boy. Other less serious complications may have occurred in other boys, but not been reported. CONCLUSION: Complications following male circumcision in Scandinavia were relatively rare, but serious complications did occur. Based on the analyses of the severe cases, we argue that circumcision should only be performed at hospitals with 24-hour emergency departments. PMID- 26991602 TI - Rapid lateral-flow immunoassay for the quantum dot-based detection of puerarin. AB - In this study, a rapid (within 10min) quantitative lateral-flow immunoassay using a quantum dots (QDs)-antibody probe was developed for the analysis of puerarin (PUE) in water and biological samples. The competitive immunoassay was based on anti-PUE monoclonal antibody conjugated with QDs (detection reagent). Secondary antibody was immobilized on one end of a nitrocellulose membrane (control line) and PUE-bovine serum albumin conjugate was immobilized on the other end (test line). In the quantitative experiment, the detection results were scanned using a membrane strip reader and a detection curve (regression equation: y= 0.11ln(x)+0.979, R(2)=0.9816) representing the averages of the scanned data was obtained. This curve was linear from 1 to 10MUg/mL. The IC50 value was 75.58ng/mL and the qualitative detection limit of PUE was 5.8ng/mL. The recovery of PUE added to phosphate-buffered saline and biological samples was in the range of 97.38-116.56%. To our knowledge, this is the first report of the quantitative detection of a natural product by QDs-based immunochromatography, which represents a powerful tool for rapidly screening PUE in plant materials and other biological samples. PMID- 26991603 TI - The IsoStretcher: An isotropic cell stretch device to study mechanical biosensor pathways in living cells. AB - Mechanosensation in many organs (e.g. lungs, heart, gut) is mediated by biosensors (like mechanosensitive ion channels), which convert mechanical stimuli into electrical and/or biochemical signals. To study those pathways, technical devices are needed that apply strain profiles to cells, and ideally allow simultaneous live-cell microscopy analysis. Strain profiles in organs can be complex and multiaxial, e.g. in hollow organs. Most devices in mechanobiology apply longitudinal uniaxial stretch to adhered cells using elastomeric membranes to study mechanical biosensors. Recent approaches in biomedical engineering have employed intelligent systems to apply biaxial or multiaxial stretch to cells. Here, we present an isotropic cell stretch system (IsoStretcher) that overcomes some previous limitations. Our system uses a rotational swivel mechanism that translates into a radial displacement of hooks attached to small circular silicone membranes. Isotropicity and focus stability are demonstrated with fluorescent beads, and transmission efficiency of elastomer membrane stretch to cellular area change in HeLa/HEK cells. Applying our system to lamin-A overexpressing fibrosarcoma cells, we found a markedly reduced stretch of cell area, indicative of a stiffer cytoskeleton. We also investigated stretch activated Ca(2+) entry into atrial HL-1 myocytes. 10% isotropic stretch induced robust oscillating increases in intracellular Fluo-4 Ca(2+) fluorescence. Store operated Ca(2+) entry was not detected in these cells. The Isostretcher provides a useful versatile tool for mechanobiology. PMID- 26991605 TI - Stiffness of Intact Endothelial Cells From Fresh Aortic Bifurcations of Atherosclerotic Rabbits-Atomic Force Microscopic Study. AB - Stiffness of intact endothelial cells (ECs) in the abdominal aorta (AA) and in the medial and lateral wall of the common iliac artery (CIA(Medial) and CIA(Lateral), respectively), which were freshly obtained from cholesterol-fed rabbits, were measured with an atomic force microscopic indentation method. In the areas away from atherosclerotic plaques (Off-plaque), ECs were significantly stiffer in CIA(Medial) than in the other two locations; this result was similar to that from normal diet-fed animals. On the other hand, there were no significant differences in the stiffness of ECs located on atherosclerotic plaques (On-plaque) among the three sites; the stiffness was equal to those in "Off-plaque" wall of CIA(Lateral) and AA. Moreover, the stiffness of ECs covering plaques decreased with the progression of atherosclerosis. The precise quantification of the stiffness of vascular ECs would provide a better understanding of cellular remodeling and adaptation in atherosclerosis. J. Cell. Physiol. 232: 7-13, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26991606 TI - Posterior musculofascial reconstruction after radical prostatectomy: an updated systematic review and a meta-analysis. AB - To evaluate the influence of posterior musculofascial plate reconstruction (PR) on early return of continence after radical prostatectomy (RP); an updated systematic review of the literature. A systematic review of the literature was performed in June 2015, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and searching Medline, Embase, Scopus and Web of Science databases. We searched the terms posterior reconstruction prostatectomy, double layer anastomosis prostatectomy across the 'Title' and 'Abstract' fields of the records, with the following limits: humans, gender (male), and language (English). The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. A meta-analysis of the risk ratios estimated using data from the selected studies was performed. In all, 21 studies were identified, including three randomised controlled trials. The overall analysis of comparative studies showed that PR improved early continence recovery at 3-7, 30, and 90 days after catheter removal, while the continence rate at 180 days was statistically but not clinically affected. Statistically significantly lower anastomotic leakage rates were described after PR. There were no significant differences for positive surgical margins rates or for complications such as acute urinary retention and bladder neck stricture. The analysis confirms the benefits at 30 days after catheter removal already discussed in the review published in 2012, but also shows a significant advantage in terms of urinary continence recovery in the first 90 days. A multicentre prospective randomised controlled trial is currently being conducted in several institutions around the world to better assess the effectiveness of PR in facilitating an earlier recovery of postoperative urinary continence. PMID- 26991607 TI - In silico characterization of DNA motifs associated with the differential expression of the ornithine decarboxylase gene during in vitro cystocarp development in the red seaweed Grateloupia imbricata. AB - To gain a better understanding of the regulatory mechanism(s) modulating expression of the ornithine decarboxylase gene ODC during cystocarp development in the red seaweed Grateloupia imbricata, DNA motifs found in the 5'-upstream region of the gene were identified by in silico analysis. In addition, when infertile G. imbricata thalli were treated with ethylene, methyl jasmonate, or light as an elicitor of cystocarp development, different ODC expression patterns were observed. ODC expression correlated with (i) the elicitation (treatment) period and the period post-treatment just prior to observation of the first visible developing cystocarps (disclosure period), and (ii) the type of elicitor. Ethylene and light activated ODC expression during the elicitation period, and methyl jasmonate activated its expression during the disclosure period, suggesting that initiation and cystocarp development may involve more than one signaling pathway. In addition, expression of ODC was 450-fold greater when thalli were stimulated by ethylene compared with untreated control thalli, suggesting that G. imbricata mounts an efficient response to sense and activate ethylene-responsive signaling pathways. The patterns of differential ODC expression induced by the different elicitors during cystocarp development might provide an useful tool for characterizing the precise transcriptional regulation of ODC in G. imbricata. PMID- 26991609 TI - A new nomogram score for predicting surgery-related pressure ulcers in cardiovascular surgical patients. AB - The aim of this study was to build a new nomogram score for predicting surgery related pressure ulcers (SRPU) in cardiovascular surgical patients. We performed a prospective cohort study among consecutive patients with cardiovascular surgery between January 2015 and December 2015. Univariate and multivariate logistic regression was used to analyse the risk factors for SRPU. A nomogram-predicting model was built based on the logistic regression model. Then, calibration and discrimination were tested. A total of 149 patients with cardiovascular surgery were included in the study. Thirty-seven patients developed SRPUs, with an incidence rate of 24.8% (95%CI: 18.1-32.6%). The logistic regression model for predicting SRPU with four risk factors was Logit(P) = (1.861 * VDH, OR 2.174 * CAD, OR 1.747 * TAA) - 0.029 * weight + 0.005 * surgery duration + 1.241 * perioperative corticosteroids administration (P = 0.003, R2 = 0.1181). The goodness-of-fit test (Pearson chi2 = 150.69, P = 0.217) indicated acceptable calibration, and the C-index (0.725) indicated moderate discrimination. When the probability cut-off is 0.25 (total score 12), the nomogram model has the best sensitivity and specificity in predicting SRPU. We established a new nomogram model that can provide an individual prediction of SRPU in cardiovascular surgical patients. When the probability is more than 0.25 (total score 12), the cardiovascular surgery patients should be considered at high-risk. PMID- 26991608 TI - Long-term treatment with methylphenidate for fatigue after traumatic brain injury. AB - OBJECTIVES: Traumatic brain injury (TBI) may cause long-lasting post-concussive symptoms, such as mental fatigue and concentration difficulties, and this may become the main hindrance for returning to work and studies. There is currently no effective treatment for long-lasting mental fatigue. In this hypothesis generating study, the long-term effects of methylphenidate on mental fatigue, cognitive function, and safety were assessed. MATERIALS & METHODS: Thirty participants who suffered from long-term post-concussion symptoms after a mild TBI or moderate TBI and who had reported positive effects with methylphenidate during an initial phase of this follow-up study were treated with methylphenidate for a further six months. RESULTS: After six-month follow-up, effects on Mental Fatigue Scale (MFS), depression, anxiety, and cognitive function (processing speed, attention, working memory) were significantly improved compared to baseline data (P < 0.001, respectively). Heart rate was significantly increased (P = 0.01), while blood pressure was not changed. CONCLUSIONS: Individuals suffering from prolonged symptoms after TBI reported reduced mental fatigue and improved cognitive functions with long-term methylphenidate treatment. It is suggested that methylphenidate can be a treatment option for long-term mental fatigue and cognitive impairment after a TBI, but further randomized control research is warranted. PMID- 26991610 TI - Effects of the combination of decitabine and homoharringtonine in SKM-1 and Kg-1a cells. AB - The methylation inhibitor decitabine (DAC) has great therapeutic value for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, DAC monotherapy is associated with relatively low rates of overall response and complete remission. Previous studies have shown promising results for combination treatment regimens including DAC. Homoharringtonine (HHT), an alkaloid from Chinese natural plants and Cephalotaxus, has demonstrated potential for leukemia treatment. Our studies have suggested that the combination of DAC and HHT has synergistic effects for inhibiting the viability of SKM-1 and Kg-1a cells. This combination leads to enhanced inhibition of colony formation and apoptosis induction compared with DAC alone in SKM-1 but not Kg-1a cells. Only high-dose DAC and HHT significantly up-regulate caspase-3 and caspase-9 and inhibit BCL-XL in the SKM-1 cell line. The combined effects of DAC plus HHT on apoptosis may not only depend on regulation of the apoptosis-related genes we examined but others as well. HHT had no demethylation effects, and HHT in combination with DAC had no enhanced effects on hypomethylation and DNMT1, DNMT3A and DNMT3B mRNA expression in SKM-1 cells. Overall, these results suggest that DAC used in combination with HHT may have clinical potential for MDS treatment. PMID- 26991611 TI - Blood Products, Crystalloids, and Rapid Infusion: An Experimental Study. AB - BACKGROUND: Electromagnetic coil overheating, deformation, occlusion, and rupture during rapid infuser use have been previously reported. Although the etiology is unclear, prolonged machine use and reconstitution of citrated blood components with crystalloid solutions in the reservoir have been implicated. Lactated Ringer's (LR) solution is of particular concern as a diluent because of its calcium content. We sought to reproduce this failure mode using different infusion rates and different combinations of fluids for blood product reconstitution in the reservoir. We also introduced calcium chloride (CaCl2) to the mix to determine its role in macroscopic clot formation. METHODS: In this in vitro study, we conducted 2 series of experiments using the Belmont FMS 2000 rapid infuser and a reservoir. In series I, we submitted a mix of 1 U fresh thawed plasma (FTP) and 1 U red blood cells (RBC) with 500 mL of LR solution, normal saline, Plasma-Lyte A, or albumin 5% to a specific pump flow sequence. If neither a pump failure mode or self-shutoff (primary outcome) nor macroscopic clot (secondary outcome) was observed during a pump flow sequence, the sequences were repeated after first adding an additional 500 mL of the initially used crystalloid or albumin and then CaCl2 beginning with 200 mg and up to 1 g to the reservoir. In series II, 7 different crystalloid-blood product combinations were tested by using a variety of pump flow sequences with the same end points. Descriptive statistics and analysis of variance were used, and data were reported as means +/- SD. RESULTS: We did not observe a Belmont pump failure mode (coil deformation, occlusion, or rupture) as previously described. In series I, the addition of CaCl2 200 mg resulted in macroscopic clots in 9 of 10 experiments (95% confidence interval, 0.55-0.99). The time to clot formation was 9.1 +/- 2.3 minutes (99% confidence interval, 6.74-11.46) and did not differ between solutions used for component reconstitution. In series II, adding variable amounts of CaCl2 to 4 different combinations of FTP/RBC with Plasma-Lyte A or LR solution led to clot formation. The use of only FTP in 2 experiments with either LR solution or normal saline resulted in formation of a fibrin clot. In 1 experiment of LR solution mixed with RBCs alone, no clot was observed even after addition of 1 g CaCl2. After the observation of clot in the reservoir, the fluid empty alarm occurred once in series I, the overheating alarm occurred once in series II, and the high-pressure alarms occurred 3 times in each series, all accompanied by self-shutoff. CONCLUSIONS: In this in vitro study, we were unable to reproduce the failure mode characterized by coil overheating, deformation, and rupture previously reported with use of the FMS 2000. Addition of CaCl2 in the range of 200 mg caused macroscopic coagulation in the reservoir when added to crystalloids or albumin mixed with different combinations of blood products containing FTP. PMID- 26991612 TI - Lung Perfusion and Ventilation During Cardiopulmonary Bypass Reduces Early Structural Damage to Pulmonary Parenchyma. AB - BACKGROUND: It is unclear whether maintaining pulmonary perfusion and ventilation during cardiopulmonary bypass (CPB) reduces pulmonary inflammatory tissue injury compared with standard CPB where the lungs are not ventilated and are minimally perfused. In this study, we tested the hypothesis that maintenance of lung perfusion and ventilation during CPB decreases regional lung inflammation, which may result in less pulmonary structural damage. METHODS: Twenty-seven pigs were randomly allocated into a control group only submitted to sternotomy (n = 8), a standard CPB group (n = 9), or a lung perfusion group (n = 10), in which lung perfusion and ventilation were maintained during CPB. Hemodynamics, gas exchanges, respiratory mechanics, and systemic interleukins (ILs) were determined at baseline (T0), at the end of 90 minutes of CPB (T90), and 180 minutes after CPB (T180). Bronchoalveolar lavage (BAL) ILs were obtained at T0 and T180. Dorsal and ventral left lung tissue samples were examined for optical and electron microscopy. RESULTS: At T90, there was a transient reduction in PaO2/FIO2 in CPB (126 +/- 64 mm Hg) compared with the control and lung perfusion groups (296 +/- 46 and 244 +/- 57 mm Hg; P < 0.001), returning to baseline at T180. Serum ILs were not different among the groups throughout the study, whereas there were significant increases in BAL IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in both CPB and lung perfusion groups compared with the control group. Polymorphonuclear counts within the lung tissue were smaller in the lung perfusion group than in the CPB group (P = 0.006). Electron microscopy demonstrated extrusion of surfactant vesicles into the alveolar spaces and thickening of the alveolar septa in the CPB group, whereas alveolar and capillary histoarchitecture was better preserved in the lung perfusion group. CONCLUSIONS: Maintenance of lung perfusion and ventilation during CPB attenuated early histologic signs of pulmonary inflammation and injury compared with standard CPB. Although increased compared with control animals, there were no differences in serum or BAL IL in animals receiving lung ventilation and perfusion during CPB compared with standard CPB. PMID- 26991613 TI - Equalization of Intracardiac Pressures in Cardiac Tamponade. PMID- 26991614 TI - Thoracic Aortic Stent Migration to False Lumen in Aortic Dissection Detected by Intraoperative Transesophageal Echocardiography. PMID- 26991615 TI - The Effect of Preoperative Gabapentin on Postoperative Nausea and Vomiting: A Meta-Analysis. AB - BACKGROUND: Preoperative gabapentin has been shown to improve postoperative pain and limit reliance on opioid analgesia. On the basis of an alternative mechanism, our group investigated the ability of preoperative gabapentin to prevent postoperative nausea and vomiting (PONV). METHODS: We performed a meta-analysis of trials that reported outcomes on the effect of preoperative gabapentin on PONV end points in patients undergoing general anesthesia. In our primary analysis, we calculated the pooled antiemetic effects of preoperative gabapentin in studies with PONV as the primary end point. In our secondary analysis, we calculated the pooled effects in trials involving preoperative gabapentin that reported on the side effects, nausea and vomiting. RESULTS: Among the trials designed with PONV as a primary end point (8 trials; n = 838), preoperative gabapentin was associated with a significant reduction in PONV (risk ratio [RR] = 0.60; 99% confidence interval [CI], 0.50-0.72; P < 0.0001), nausea (RR = 0.34; 99% CI, 0.20 0.56; P < 0.0001), and vomiting (RR = 0.34; 99% CI, 0.19-0.61; P = 0.0002) at 24 hours. Among all included trials (44 trials; n = 3489) that reported on the side effects, nausea and vomiting, similar reductions were noted in PONV with preoperative gabapentin administration. Subgroup analysis of trials excluding repeat dosing, thiopental induction, and nitrous oxide maintenance and including high-risk surgery resulted in similar PONV efficacy. Preoperative gabapentin is also associated with significantly increased rates of postoperative sedation (RR = 1.22; 95% CI, 1.02-1.47; P = 0.03) compared with control. CONCLUSIONS: Preoperative gabapentin is associated with a significant reduction in PONV among studies designed to investigate this end point. Preoperative gabapentin should be considered not only as part of a multimodal approach to postoperative analgesia, but also for prevention of PONV. PMID- 26991616 TI - Tranexamic Acid Compared with Placebo for Reducing Total Blood Loss in Hip Replacement Surgery: A Randomized Clinical Trial. AB - BACKGROUND: Tranexamic acid (TXA) reduces bleeding in patients undergoing hip replacement surgery, but optimal doses and timing have yet to be established. Our primary objective in this study was to assess total blood loss 48 hours after surgery with different regimens. METHODS: This was a multicenter, parallel-group, randomized, placebo-controlled clinical trial that included all ASA physical status I to III patients undergoing unilateral total hip replacement surgery who met the inclusion criteria. Patients were randomly allocated to 1 of 3 groups: a single-dose group (15 mg/kg TXA before the start of surgery and saline 3 hours later after the start of surgery), a 2-dose group (10 m/kg TXA before and 10 mg/kg of TXA 3 hours after the start of surgery), and a control group (saline before and 3 hours after the start of surgery). Total blood loss was calculated using a formula considering hematocrit values and blood transfusions received. RESULTS: We included 108 patients in the study. Total blood loss volumes up to day 2 were 1377 +/- 689, 1308 +/- 641, and 2215 +/- 1136 mL in the single-dose, 2 dose and control groups, respectively (P < 0.001 between the placebo and the experimental groups). Blood transfusions were given to 22.9% of patients (n = 8) in the single-dose group, 11.1% (n = 4) in the 2-dose group, and 37.8% (n = 14) in the control group (P = 0.028). CONCLUSIONS: A single preoperative dose of TXA or 2 infusions of a lower dose, preoperatively and then after 3 hours after the start of surgery, resulted in lower blood loss during the first 2 days after surgery and less need for blood transfusion, with good levels of safety. PMID- 26991617 TI - Distinct Hypnotic Recoveries After Infusions of Methoxycarbonyl Etomidate and Cyclopropyl Methoxycarbonyl Metomidate: The Role of the Metabolite. AB - BACKGROUND: Methoxycarbonyl etomidate (MOC-etomidate) and cyclopropyl methoxycarbonyl metomidate (CPMM) are rapidly metabolized "soft" etomidate analogs. CPMM's duration of hypnotic effect is context insensitive, whereas MOC etomidate's is not. In this study, we tested the hypothesis that CPMM's effect is context insensitive because, unlike MOC-etomidate, its metabolite fails to reach physiologically important concentrations in vivo even with prolonged continuous infusion. METHODS: We compared the potencies with which MOC-etomidate and CPMM activate alpha1(L264T)beta3gamma2 gamma-aminobutyric acid type A receptors and induce loss-of-righting reflexes (i.e., produce hypnosis) in tadpoles with those of their metabolites (MOC-etomidate's carboxylic acid metabolite [MOC-ECA] and CPMM's carboxylic acid metabolite [CPMM-CA], respectively). We measured metabolite concentrations in the blood and cerebrospinal fluid of Sprague-Dawley rats on CPMM infusion and compared them with those achieved with MOC-etomidate infusion. We measured the rates with which brain tissue from Sprague-Dawley rats metabolize MOC-etomidate and CPMM. RESULTS: Both analogs and their metabolites enhanced gamma-aminobutyric acid type A receptor function and induced loss-of righting reflexes in a concentration-dependent manner. However, in these 2 assays, CPMM-CA's potency relative to its parent hypnotic was approximately 1:4900 and 1:1900, respectively, whereas MOC-ECA's was only approximately 1:415 and 1:390, respectively. With 2-hour CPMM infusions, CPMM-CA reached respective concentrations in the blood and cerebrospinal fluid that were 2 and >3 orders of magnitude lower than that which produced hypnosis. CPMM was metabolized by the brain tissue at a rate that is approximately 1/15th that of MOC-etomidate. CONCLUSIONS: Hypnotic recovery after CPMM administration is context insensitive because its metabolite does not accumulate to hypnotic levels in the central nervous system. This reflects the very large potency ratio between CPMM and CPMM CA and the resistance of CPMM to metabolism by esterases present in the brain. PMID- 26991618 TI - Increased Intraoperative Fluid Administration Is Associated with Severe Primary Graft Dysfunction After Lung Transplantation. AB - BACKGROUND: Severe primary graft dysfunction (PGD) is a major cause of early morbidity and mortality in patients after lung transplantation. The etiology and pathophysiology of PGD is not fully characterized and whether intraoperative fluid administration increases the risk for PGD remains unclear from previous studies. Therefore, we tested the hypothesis that increased total intraoperative fluid volume during lung transplantation is associated with the development of grade-3 PGD. METHODS: This retrospective cohort analysis included patients who had lung transplantation at the Cleveland Clinic between January 2009 and June 2013. We used multivariable logistic regression with adjustment for donor, recipient, and perioperative confounding factors to examine the association between total intraoperative fluid administration and development of grade-3 PGD in the initial 72 postoperative hours. Secondary outcomes included time to initial extubation and intensive care unit length of stay. RESULTS: Grade-3 PGD occurred in 123 of 494 patients (25%) who had lung transplantation. Patients with grade-3 PGD received a larger volume of intraoperative fluid (median 5.0 [3.8, 7.5] L) than those without grade-3 PGD (3.9 [2.8, 5.2] L). Each intraoperative liter of fluid increased the odds of grade-3 PGD by approximately 22% (adjusted odds ratio, 1.22; 95% confidence interval [CI], 1.12-1.34; P <0.001). The volume of transfused red blood cell concentrate was associated with grade-3 PGD (1.1 [0.0, 1.8] L for PGD-3 vs 0.4 [0.0, 1.1 for nongrade-3 PGD] L; adjusted odds ratio, 1.7; 95% CI, 1.08-2.7; P = 0.002). Increased fluid administration was associated with longer intensive care unit stay (adjusted hazard ratio, 0.92; 97.5% CI, 0.88-0.97; P < 0.001) but not with time to initial tracheal extubation (hazard ratio, 0.97; 97.5% CI, 0.93-1.02; P = 0.17). CONCLUSIONS: Increased intraoperative fluid volume is associated with the most severe form of PGD after lung transplant surgery. Limiting fluid administration may reduce the risk for development of grade-3 PGD and thus improve early postoperative morbidity and mortality after lung transplantation. PMID- 26991619 TI - Hemodynamics of Phenylephrine Infusion Versus Lower Extremity Compression During Spinal Anesthesia for Cesarean Delivery: A Randomized, Double-Blind, Placebo Controlled Study. AB - BACKGROUND: Phenylephrine infusion is the current first-line choice for prevention of spinal hypotension during cesarean delivery. The optimal dosage regimen is still undetermined. A mechanical alternative, lower limb wrapping, has been examined in a few small studies showing moderate success. In this trial, we compared the effect of leg wrapping with low-dose phenylephrine infusion and with placebo treatment on systolic arterial blood pressure during spinal anesthesia for cesarean delivery. METHODS: In this randomized, double-blinded, placebo controlled study, healthy women received either phenylephrine (n = 38; initial bolus of 0.25 MUg kg and infusion of 0.25 MUg kg min), leg wrapping (n = 38), or no treatment (control; n = 36) during spinal anesthesia for elective cesarean delivery. LiDCOplus was used for continuous minimally invasive hemodynamic monitoring. The extent of decrease in systolic arterial blood pressure (for 13 minutes after spinal induction) was the primary outcome. Cardiac output, systemic vascular resistance, stroke volume, heart rate, neonatal acid-base status, and Apgar score were secondary outcome variables. Mixed model analysis of continuous hemodynamic trends during the first 13 minutes after induction of spinal anesthesia was performed. RESULTS: In the phenylephrine group, the decrease in systolic arterial blood pressure was significantly less (difference in rate of change, 0.09 mm Hg 5 s; 95% confidence interval, 0.02-0.16; P = 0.013); systemic vascular resistance (P < 0.001) was significantly higher; stroke volume (P = 0.41) was similar; and heart rate (P = 0.002) and cardiac output (P < 0.001) were significantly lower compared with the leg wrapping group. Compared with control, the leg wrapping group had a significantly smaller decrease in systolic arterial blood pressure (0.39 mm Hg 5 s; 95% confidence interval, 0.32-0.46; P < 0.001), higher stroke volume (P < 0.001), and higher cardiac output (P = 0.001). CONCLUSIONS: An initial bolus of phenylephrine followed by a low-dose phenylephrine infusion was superior to leg wrapping and no intervention for the prevention of hypotension during spinal anesthesia for cesarean delivery. Phenylephrine prevented hypotension primarily by restoring systemic vascular resistance and did not cause hypertension or a clinically relevant reduction in cardiac output. Leg wrapping prevented hypotension compared with no intervention by limiting modest early spinal anesthesia-mediated venodilation. PMID- 26991620 TI - Pharyngeal Oxygen Insufflation During AirTraq Laryngoscopy Slows Arterial Desaturation in Infants and Small Children. AB - BACKGROUND: The extent to which insufflation of oxygen into the posterior pharynx during laryngoscopy prolongs adequate saturation in infants and small children remains unknown. Therefore, we compared oxygen saturation over time in preoxygenated small children with and without posterior pharynx oxygen insufflation. METHODS: After induction of anesthesia with sevoflurane and propofol, infants and small children were preoxygenated with 100% oxygen for 3 minutes. An AirTraq laryngoscope size 0 or 1 with an appropriately sized cuffed endotracheal tube positioned in the side channel was prepared. Oxygen tubing was connected to the endotracheal U-shaped tube. However, oxygen at a flow of 4 L/min was provided only to half of the randomly selected participating patients. The trachea was intubated, the tube cuff was inflated, and the laryngoscope was removed from the mouth. The oxygen tubing was disconnected from the endotracheal tube and left exposed to ambient air until oxygen saturation decreased to 95%. Thereafter, patients' lungs were manually ventilated with 100% oxygen until SpO2 returned to 100%. Subsequent anesthetic management was at the discretion of the attending anesthesiologist. RESULTS: Laryngoscopy took a median of 60 (Q1-Q3, 40 90) seconds. The mean time to 95% oxygen saturation was (mean +/- SD) 166 +/- 47 seconds in the oxygen insufflation group and 131 +/- 39 seconds in small children without insufflation. Oxygen insufflation prolonged the mean time for saturation to decrease from 100% to 95% by an estimated 35 (95% confidence interval, 10-60) seconds, P = 0.01. CONCLUSIONS: Adding posterior pharyngeal oxygen insufflation to conventional preoxygenation prolonged the period of adequate oxygen saturation in infants and small children by an amount that is potentially clinically important. PMID- 26991621 TI - Implications of Patient Age and ASA Physical Status for Operating Room Management Decisions. AB - BACKGROUND: In elderly, high-risk patients, operating room (OR) turnaround times are especially difficult to estimate, and the managerial implications of patient age and ASA physical status for OR management decisions remain unclear. We hypothesized that evaluating patient age and ASA physical status in the right model would improve accuracy of turnaround time estimates and, thus, would have decisive implications for OR management. METHODS: By using various multivariate techniques, we modeled turnaround times of 13,632 OR procedures with respect to multiple variables including surgical list, age, ASA physical status, duration of the procedure, and duration of the preceding procedure. We first assessed correlations and general descriptive features of the data. Then, we constructed decision tables for OR management consisting of 50th and 95th percentiles of age/ASA-dependent estimates of turnaround times. In addition, we applied linear and generalized linear multivariate models to predict turnaround times. The forecasting power of the models was assessed in view of single cases but also in view of critical managerial key figures (50th and 95th percentile turnaround times). The models were calibrated on 80% of the data, and their predictive value was tested on the remaining 20%. We considered our data in a Monte Carlo simulation to deduce actual reductions of overutilized OR time when applying the results as presented in this work. RESULTS: Using the best models, we achieved an increase in predictive accuracy of 7.7% (all lists), ranging from 2.5% (general surgery) to 21.0% (trauma surgery) relative to age/ASA-independent medians of turnaround times. All models decreased the forecasting error, signifying a relevant increase in planning accuracy. We constructed a management decision table to estimate age/ASA-dependent turnaround time for OR scheduling at our hospital. CONCLUSIONS: The decision tables allow OR managers at our hospital to schedule procedures more accurately. Evaluation of patient age and ASA physical status as variables can help to better predict turnaround times, which can facilitate scheduling, for example, to schedule overlapping induction rooms, to reduce overutilized OR time by optimizing allocation of patients to several ORs, and to improve logistics of prioritizing transportation of advanced age/high ASA physical status patients to the OR. PMID- 26991622 TI - Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique. AB - BACKGROUND: Epidural anesthesia may attenuate the sympathetic hyperactivity and stress response from surgery. In this study, we compared the stress response, hemodynamic variables, and recovery profiles of patients undergoing total IV anesthesia (TIVA) and intraoperative dexmedetomidine with those receiving epidural anesthesia and TIVA. METHODS: Ninety patients undergoing elective open gastrectomy under TIVA were recruited. The dexmedetomidine group (group D, n = 30) received IV dexmedetomidine 0.6 MUg/kg before the induction of general anesthesia, followed by dexmedetomidine 0.4 MUg/kg/h until peritoneal closure. The control group (group C, n = 30) received volume-matched normal saline infusion as placebo. The epidural group (group E, n = 30) received epidural anesthesia with 0.375% ropivacaine combined with TIVA. The hemodynamic variables and recovery characteristics during emergence were evaluated. Blood samples for norepinephrine (NE), epinephrine (E), cortisol (Cor), and cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-6, and IL-10) were obtained before the administration of dexmedetomidine or epidural anesthesia (baseline), immediately after tracheal intubation, upon incision, at the time of celiac exploration, and at tracheal extubation. RESULTS: Compared with group E, there were no differences in the plasma concentration levels of NE, E, Cor, and cytokines (TNF-alpha, IL-6, and IL-10) in group D at all time points. The levels of NE and E in groups D and E were significantly lower than that in group C, at all time points following induction (all P < 0.0001 except at incision which were P = 0.001 and P = 0.004), and the level of Cor in groups D and E was significantly lower than that in group C at celiac exploration (P = 0.017 and P = 0.019) and immediately after tracheal extubation (P < 0.0001). The levels of TNF alpha, IL-6, and IL-10 increased after the celiac exploration in the 3 groups. The levels of plasma TNF-alpha, IL-6, and IL-6/IL-10 ratio were higher in group C than in groups D and E at celiac exploration and tracheal extubation (all P < 0.0001 except at celiac exploration which were P = 0.005 and P =0.038 for TNF alpha and P = 0.049 and P = 0.038 for IL-6/IL-10 ratio). In group D, the heart rate was significantly slower after commencing dexmedetomidine and remained significantly slower throughout the operative course (all P < 0.0001 except at tracheal extubation which was P = 0.032). The number of patients who required intervention because of intraoperative hypotension was significantly higher in group E (36.7%) compared with groups D and C (13.3% and 10.0%) (P = 0.037, P = 0.015). The times to eye opening and tracheal extubation were similar in all groups. There were fewer incidences of agitation in group D (6.7 %) than in group C (26.6%) (P = 0.038). CONCLUSIONS: When used in conjunction with TIVA, intraoperative dexmedetomidine blunts surgical stress responses to an extent comparable to combined epidural and general anesthesia without compromising hemodynamic stability and with minimal adverse effects during the intraoperative period. PMID- 26991623 TI - The Mandate to Measure Patient Experience: How Can Patients "Value" Anesthesia Care? PMID- 26991624 TI - What Is the PROPPR Transfusion Strategy in Trauma Resuscitation? PMID- 26991625 TI - Color Coding, Labeling, and Evidence for Safety Gains. PMID- 26991626 TI - In Response. PMID- 26991627 TI - SOAP Delivers: Options for Labor Pain. PMID- 26991628 TI - Overregulation: A Call to Arms. PMID- 26991629 TI - Regarding "2-Deoxy-D-Glucose Enhances Anesthetic Effects in Mice". PMID- 26991630 TI - In Response. PMID- 26991632 TI - The use of coancestry based on shared segments for maintaining genetic diversity. AB - We have evaluated the use of genomic coancestry coefficients based on shared segments for the maintenance of genetic diversity through optimal contributions methodology for populations of three different Austrian cattle breeds. This coancestry measure has been compared with the genomic coancestry coefficient calculated on a SNP-by-SNP basis and with pedigree-based coancestry. The regressions of the shared segments coancestry on the other two coefficients suggest that the former mainly reflect Identity By Descent but with the advantage over pedigree-based coancestry of providing the realized Identity By Descent rather than an expectation. The effective population size estimated from the rate of coancestry based on shared segments was very similar to those obtained with the other coefficients and of small magnitude (from 26.24 to 111.90). This result highlights the importance of implementing active management strategies to control the increase of inbreeding and the loss of genetic diversity in livestock breeds, even when the population size is reasonably large. One problem for the implementation of coancestry based on shared segments is the need of estimating the gametic phases of the SNPs which, given the techniques used to obtain the genotypes, are a priori unknown. This study shows, through computer simulations, that using estimates of gametic phases for computing coancestry based on shared segments does not lead to a significant loss in the diversity maintained. This has been shown to be true even when the size of the population is very small as it is usually the case in populations subjected to conservation programmes. PMID- 26991631 TI - Patient-related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS-CAN prospective study. AB - Little is known about the effects of frailty, disability and physical functioning on the clinical outcomes for myelodysplastic syndromes (MDS). We investigated the predictive value of these factors on overall survival (OS) in 445 consecutive patients with MDS and chronic monomyelocytic leukaemia (CMML) enrolled in a multi centre prospective national registry. Frailty, comorbidity, instrumental activities of daily living, disability, quality of life, fatigue and physical performance measures were evaluated at baseline and were added as covariates to conventional MDS-related factors as predictors of OS in Cox proportional hazards models. The median age was 73 years, and 79% had revised International Prognostic Scoring System (IPSS-R) risk scores of intermediate or lower. Frailty correlated only modestly with comorbidity. OS was significantly shorter for patients with higher frailty and comorbidity scores, any disability, impaired grip strength and timed chair stand tests. By multivariate analysis, the age-adjusted IPSS-R, frailty (Hazard ratio 2.7 (95% confidence interval [CI] 1.7-4.2), P < 0.0001) and Charlson comorbidity score (Hazard ratio 1.8 (95% CI 1.1-2.8), P = 0.01) were independently prognostic of OS. Incorporation of frailty and comorbidity scores improved risk stratification of the IPSS-R by 30% and 5%, respectively. These data demonstrate for the first time, the importance of considering frailty in prognostic models and a potential target for therapeutic intervention in optimizing clinical outcomes in older MDS patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02537990. PMID- 26991633 TI - Gd-TEMDO: Design, Synthesis, and MRI Application. AB - A simple Ugi tetrazole multicomponent reaction allows the synthesis of a novel macrocyclic cyclen derivative with four appendant tetrazole arms in just two steps in excellent yields. This ligand, called TEMDO, turns out to have a high complexation affinity with lanthanoid metals. Here we describe the design, synthesis, solid-state structure, binding constant, and some MRI applications of the Gd-TEMDO complex as the first example of a congeneric family of oligo-amino tetrazoles. PMID- 26991634 TI - Total synthesis of mambalgin-1/2/3 by two-segment hydrazide-based native chemical ligation. AB - Mambalgins are a class of 57-residue polypeptide toxins isolated from the venom of the African mamba. They exhibit potent analgesic effects by inhibiting the acid-sensing ion channels. Classified as members of the family of three-finger toxins, mambalgins contain four pairs of disulfide bridges that help to stabilize the three-finger scaffold. Here, we report the chemical synthesis of functional mambalgin-1/2/3 by using one-step two-segment hydrazide-based native chemical ligation. The two-segment ligation approach reported here may enable efficient production of mambalgin toxins. These synthetic mambalgins are useful compounds for development of diagnostic or therapeutic reagents. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 26991635 TI - Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni. AB - An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotron-based imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm's tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm. PMID- 26991636 TI - Indirect three-dimensional printing: A method for fabricating polyurethane-urea based cardiac scaffolds. AB - Biomaterial scaffolds are a key part of cardiac tissue engineering therapies. The group has recently synthesized a novel polycaprolactone based polyurethane-urea copolymer that showed improved mechanical properties compared with its previously published counterparts. The aim of this study was to explore whether indirect three-dimensional (3D) printing could provide a means to fabricate this novel, biodegradable polymer into a scaffold suitable for cardiac tissue engineering. Indirect 3D printing was carried out through printing water dissolvable poly(vinyl alcohol) porogens in three different sizes based on a wood-stack model, into which a polyurethane-urea solution was pressure injected. The porogens were removed, leading to soft polyurethane-urea scaffolds with regular tubular pores. The scaffolds were characterized for their compressive and tensile mechanical behavior; and their degradation was monitored for 12 months under simulated physiological conditions. Their compatibility with cardiac myocytes and performance in novel cardiac engineering-related techniques, such as aggregate seeding and bi-directional perfusion, was also assessed. The scaffolds were found to have mechanical properties similar to cardiac tissue, and good biocompatibility with cardiac myocytes. Furthermore, the incorporated cells preserved their phenotype with no signs of de-differentiation. The constructs worked well in perfusion experiments, showing enhanced seeding efficiency. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1912-1921, 2016. PMID- 26991637 TI - Magnetic porous carbon derived from a Zn/Co bimetallic metal-organic framework as an adsorbent for the extraction of chlorophenols from water and honey tea samples. AB - A novel magnetic porous carbon derived from a bimetallic metal-organic framework, Zn/Co-MPC, was prepared by introducing cobalt into ZIF-8. Magnetic porous carbon that possesses magnetic properties and a large specific surface area was firstly fabricated by the direct carbonization of Zn/Co-ZIF-8. The prepared magnetic porous carbon material was characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, N2 adsorption, and vibrating sample magnetometry. The prepared magnetic porous carbon was used as a magnetic solid-phase extraction adsorbent for the enrichment of chlorophenols from water and honey tea samples before high-performance liquid chromatography analysis. Several experimental parameters that could influence the extraction efficiency were investigated and optimized. Under the optimum conditions, good linearities (r > 0.9957) for all calibration curves were obtained with low limits of detection, which are in the range of 0.1-0.2 ng mL(-1) for all the analytes. The results showed that the prepared magnetic porous carbon had an excellent adsorption capability toward the target analytes. PMID- 26991638 TI - Digital Media Use and Social Engagement: How Social Media and Smartphone Use Influence Social Activities of College Students. AB - Social media and mobile phones have emerged as important platforms for college students' communication activities. This study examined how college students' psychological need to belong is associated with their use of social media and smartphones. In addition, it further investigated the effects of college students' digital media use on their social engagement. Findings revealed that students' need to belong was positively related with their use of social media and smartphones, which could further facilitate their social engagement. Moreover, the relationship between the need to belong and social engagement was mediated by college students' digital media use. This study offers empirical evidence of the positive effects of digital media on social behaviors and contributed to further understanding about the mechanisms by which need to belong leads to social engagement through digital media use. PMID- 26991639 TI - Glycaemic control in patients with diabetes and concomitant psoriasis. PMID- 26991640 TI - Asymmetric Total Synthesis of Propindilactone G, Part 3: The Final Phase and Completion of the Synthesis. AB - Two independent synthetic approaches were evaluated for the final phase of the asymmetric total synthesis of propindilactone G (1). The key steps that led to the completion of the asymmetric total synthesis included: 1) an intermolecular oxidative heterocoupling reaction of enolsilanes to link the core structure to the side chain; 2) an intermolecular Wittig reaction for the formation of the alpha,beta,gamma,delta-unsaturated ester; and 3) a regio- and stereoselective OsO4 -catalyzed dihydroxylation of an alpha,beta,gamma,delta-unsaturated enone, followed by an intramolecular lactonization reaction to afford the final product. These reactions enabled the synthesis of (+)-propindilactone G in only 20 steps. As a consequence of our synthetic studies, the structure of (+)-propindilactone G has been revised. Furthermore, the direct oxidative coupling strategy for ligation of the core of propindilactone G with its side chain may find application in the syntheses of other natural products and complex molecules. PMID- 26991641 TI - Effect of humour therapy on psychotropic medication use in nursing homes. AB - AIM: The aim of this study was to assess the effect of Play Up humour therapy on antipsychotic, benzodiazepine and antidepressant use in Australian nursing homes. METHODS: Play Up is a humour therapy program that has been implemented in Australian nursing homes. This study was an uncontrolled retrospective review of psychotropic medication charts of 406 residents in thirty-three nursing homes before and after 12 weeks of participation in Play Up. Prevalence and mean daily equivalent doses of psychotropic medication use were analysed. RESULTS: There were significant reductions from before to after the Play Up program in the prevalence of any psychotropic medication use, antipsychotic use and benzodiazepine use (P = 0.001, 0.02, 0.007, respectively). Mean daily dose equivalents of pro re nata (PRN) antipsychotics and PRN benzodiazepines significantly reduced over time (P = 0.007; P = 0.001). CONCLUSIONS: Play Up was associated with an overall decline in the use of psychotropic medications. Further trials are required to confirm and better define this association. PMID- 26991642 TI - Evaluation of a flow cytometric assay for the confirmation of heparin-induced thrombocytopenia. AB - INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenia associated with heparin therapy. The diagnosis consists of a combination of pretest probability and laboratory testing. The routinely available laboratory antigen binding assays for the detection of specific antibodies have a low HIT-positive predictive value; therefore, to exclude false positive results, one of the functional assays should be performed. Functional assays evaluate the ability of heparin/PF4 antibodies to activate the platelets. The aim of our study was to validate the flow cytometric functional assay, based on the use of anti-CD61 and anti-CD62 antibodies, as a suitable diagnostic test for HIT. METHODS: Sera from patients with a clinical suspicion of HIT were previously analyzed with screening IgG-specific ELISA, and 41 of those which were positive were selected for the functional assay. RESULTS: Our results were compared to another functional assay - the HIPA (heparin-induced platelet aggregation assay). The diagnostic specificity of the flow cytometric assay was calculated based on HIPA results and was 83%. CONCLUSION: Performing this functional test after the screening assay could significantly improve the specificity of HIT testing as heparin/PF4 antibodies are often not clinically significant. PMID- 26991643 TI - Efficacy of Adding Dutasteride to alpha-Blocker Therapy Treated Benign Prostatic Hyperplasia Patients with Small Volume Prostate (<30 mL). AB - OBJECTIVES: To assess the efficacy of dutasteride add-on therapy for patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with small prostates who have been treated with alpha-blocker therapy for >3 months. METHODS: A total of 110 men with clinical BPH were enrolled. There were 17 and 93 subjects with a prostate volume (PV) <30 and >=30 mL, respectively. All subjects had been treated with alpha-blocker therapy for >3 months. Subjective and objective clinical variables were assessed using the total International Prostate Symptom Score (IPSS-T), IPSS quality of life (IPSS-QoL), IPSS voiding subscore (IPSS-V), IPSS storage subscore (IPSS-S), overactive bladder symptom score (OABSS), PV, prostate specific antigen (PSA) level, post-void residual (PVR), and maximum flow rate (Qmax). These variables were assessed at baseline and every 3 months for 1 year. RESULTS: In the small prostate group, IPSS-T and IPSS-V showed improvements from baseline at 6 and 9 months, storage subscore at 6 months, and OABSS at 3 months, but no sustained improvements were observed. During the study period, only the IPSS QoL scores did not show any improvement. Conversly, dutasteride was significantly effective at improving IPSS-T, IPSS-V, IPSS-S, and IPSS-QoL scores throughout the study period in the large prostate BPH group. PSA levels and PV significantly decreased in both groups throughout the study. CONCLUSIONS: Benign prostatic hyperplasia in LUTS patients with small prostates did not show a sustainable benefit from the addition of dutasteride to alpha-blocker therapy. PMID- 26991644 TI - Bacterial microcompartments as metabolic modules for plant synthetic biology. AB - Bacterial microcompartments (BMCs) are megadalton-sized protein assemblies that enclose segments of metabolic pathways within cells. They increase the catalytic efficiency of the encapsulated enzymes while sequestering volatile or toxic intermediates from the bulk cytosol. The first BMCs discovered were the carboxysomes of cyanobacteria. Carboxysomes compartmentalize the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) with carbonic anhydrase. They enhance the carboxylase activity of RuBisCO by increasing the local concentration of CO2 in the vicinity of the enzyme's active site. As a metabolic module for carbon fixation, carboxysomes could be transferred to eukaryotic organisms (e.g. plants) to increase photosynthetic efficiency. Within the scope of synthetic biology, carboxysomes and other BMCs hold even greater potential when considered a source of building blocks for the development of nanoreactors or three dimensional scaffolds to increase the efficiency of either native or heterologously expressed enzymes. The carboxysome serves as an ideal model system for testing approaches to engineering BMCs because their expression in cyanobacteria provides a sensitive screen for form (appearance of polyhedral bodies) and function (ability to grow on air). We recount recent progress in the re-engineering of the carboxysome shell and core to offer a conceptual framework for the development of BMC-based architectures for applications in plant synthetic biology. PMID- 26991645 TI - MACULAR BUCKLING USING A THREE-ARMED SILICONE CAPSULE FOR FOVEOSCHISIS ASSOCIATED WITH HIGH MYOPIA. AB - PURPOSE: To investigate the safety and efficacy of a novel macular buckling technique on foveoschisis in highly myopic eyes. METHODS: Highly myopic eyes with foveoschisis, posterior staphyloma, and axial length greater than 26.5 mm, but without a full-thickness macular hole, were included. Macular buckling was performed in the included eyes using a three-armed adjustable silicon capsule. RESULTS: Eight eyes from eight patients (five women) were enrolled in this study. The mean follow-up period was 11.6 (range 9-14) months. After surgery, the best corrected visual acuity was improved in 7/8 (87.5%) eyes, optical coherence tomography imaging showed gradual anatomic improvement of macula over time. The final best-corrected visual acuity gained 21.5 early treatment diabetes retinopathy study letters from baseline on average (P = 0.014). Postoperatively, the most common complications were transiently elevated intraocular pressure (62.5%) and asymptomatic abduction limitation (100%), and the most serious complication was hemorrhagic choroidal detachment (25%). CONCLUSION: Macular buckling with a three-armed adjustable silicone capsule resulted in anatomic and visual improvement in eyes with myopic foveoschisis. PMID- 26991646 TI - INTRAVITREAL INJECTIONS OF ZIV-AFLIBERCEPT FOR DIABETIC MACULAR EDEMA: A Pilot Study. AB - PURPOSE: Diabetic macular edema is the leading cause of blindness in young adults in developed countries. Beyond metabolic control, several therapies have been studied such as laser treatment and intravitreal injections of corticosteroids or anti-vascular endothelial growth factor drugs. In terms of public health the long term treatment with the current available drugs is very expensive and new therapies with the same or better effect should be investigated. This study sought to evaluate the efficacy and safety of intravitreal injections of ziv aflibercept for the treatment of diabetic macular edema. METHODS: Seven consecutive patients with diabetic macular edema were enrolled. A complete examination, including full-field electroretinography, visual acuity, central retinal thickness, and evaluation of systemic and ocular complications, was performed before and at 24 weeks after intravitreal injections of ziv aflibercept. The seven patients were submitted to six consecutive intravitreal injections of ziv-aflibercept with a 4-week interval. RESULTS: No significant differences were found in the amplitude or implicit time of any electroretinography component after intravitreal injections of ziv-aflibercept, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at 24 weeks (P < 0.05). The central retinal thickness significantly decreased during the course of 24 weeks. CONCLUSION: Intravitreal injections of ziv-aflibercept seem to be a safe and effective treatment option for diabetic macular edema. PMID- 26991648 TI - VISUAL OUTCOME AND POOR PROGNOSTIC FACTORS IN ISOLATED IDIOPATHIC RETINAL VASCULITIS. AB - PURPOSE: To describe the clinical course, visual outcome, and prognosis of isolated, idiopathic retinal vasculitis. METHODS: Eighty patients (150 eyes) with isolated, idiopathic retinal vasculitis were included. Demographic data, clinical data, complications at the initial visit and during follow-up, fluorescein angiography, and optical coherence tomography findings were collected from the Massachusetts Eye Research and Surgery Institution (MERSI) database from September 2005 to February 2015. RESULTS: Seventy-five (93.7%) patients required treatment with immunomodulatory therapy. Of those 75 patients, 60 (75%) patients were able to achieve durable remission. Factors which were independently significant predictive of poor visual outcome were lower initial visual acuity (OR: 3.78; 95% CI: 1.75-8.16; P = 0.001), cystoid macular edema (OR: 5.54; 95% CI: 1.81-16.99; P = 0.003), and macular ischemia (OR: 5.12; 95% CI: 1.12-23.04; P = 0.036). CONCLUSION: The majority (67.25%) of our patients enjoyed a good visual outcome (most recent visit best-corrected visual acuity equal to or better than 20/40 and within one line or better from the baseline) with immunomodulatory therapy. We found that cystoid macular edema, macular ischemia, and lower best corrected visual acuity during the first consultation visit were significant independent risk factors for poor visual outcome. PMID- 26991647 TI - OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF MACULAR EDEMA AND HARD EXUDATES AND THEIR ASSOCIATION WITH LIPID SERUM LEVELS IN TYPE 2 DIABETES. AB - PURPOSE: To determine whether hyperreflective foci (HF) and macular thickness on spectral domain ocular coherence tomography are associated with lipid levels in patients with Type 2 diabetes. METHODS: Two hundred and thirty-eight participants from four sites had fundus photographs and spectral domain ocular coherence tomography images graded for hard exudates and HF, respectively. Regression models were used to determine the association between serum lipid levels and 1) presence of HF and hard exudates and 2) central subfield macular thickness, central subfield macular volume, and total macular volume. RESULTS: All patients with hard exudates on fundus photographs had corresponding HF on spectral domain ocular coherence tomography, but 57% of patients with HF on optical coherence tomography did not have hard exudates detected in their fundus photographs. Presence of HF was associated with higher total cholesterol (odds ratio = 1.13, 95% confidence interval = 1.01-1.27, P = 0.03) and higher low-density lipoprotein levels (odds ratio = 1.17, 95% confidence interval = 1.02-1.35, P = 0.02) in models adjusting for other risk factors. The total macular volume was also associated with higher total cholesterol (P = 0.009) and triglyceride (P = 0.02) levels after adjusting for other risk factors. CONCLUSION: Higher total and low density lipoprotein cholesterol were associated with presence of HF on spectral domain ocular coherence tomography. Total macular volume was associated with higher total cholesterol and triglyceride levels. PMID- 26991649 TI - EXTRAMACULAR FIBROSIS IN COATS' DISEASE. AB - PURPOSE: To determine the rate, risk factors, and outcome of extramacular fibrosis in Coats' disease. METHODS: Consecutive cases from a single center were retrospectively reviewed. Clinical characteristics and treatments were analyzed by comparative, multivariate, and survival approaches. RESULTS: Among 69 patients with Coats' disease, 28 (40.6%) showed evidence of extramacular fibrosis (mean follow-up: 58.2 months). Mean time of fibrosis onset was 17.4 months. Extent of retinal exudation and rate of exudative retinal detachment at baseline were significantly higher in eyes that developed extramacular fibrosis compared with those that did not (P < 0.001). Similarly, these parameters showed significant differences using multivariate (P < 0.05) and survival analysis (P < 0.001). Extension of telangiectasia, number of cryotherapy, or laser sessions, and treatment by anti-vascular endothelial growth factor were not associated with extramacular fibrosis. Final visual acuity was worse in patients with extramacular fibrosis (P < 0.001). The rates of tractional retinal detachment and macular fibrosis were higher in patients with extramacular fibrosis (39%.0 vs. 0% and 60.7% vs. 19.5%, respectively, P < 0.001). CONCLUSION: Extramacular fibrosis led to a worse visual prognosis and was associated with the extension of retinal exudation and the presence of exudative retinal detachment at diagnosis. Treatment should target a quick resolution of exudation to limit its development. PMID- 26991650 TI - TECHNIQUE OF LASER CHORIORETINAL ANASTOMOSIS CREATION IN CENTRAL RETINAL VEIN OCCLUSION AND SUCCESS RATE WITH A NEW PHOTOCOAGULATOR SYSTEM. AB - PURPOSE: To evaluate the success rate of laser chorioretinal anastomosis (L-CRA) creation with a new laser photocoagulator system capable of 5 watts (W) power in patients with central retinal vein occlusion (CRVO). METHODS: Patients with a treatment-naive CRVO were enrolled as part of an ongoing trial combining L-CRAs with anti-vascular endothelial growth factor treatment. RESULTS: Thirty-three patients were treated with an L-CRA developing in 29 (88%). Mean power was 2.7 W and mean time for development was 1.8 months. Each patient had two potential sites created. Eighteen patients developed 2 L-CRAs and the remaining 11 patients, one each. Of the 66 potential sites, successful L-CRAs developed at 47 sites (71%). Additional Nd:YAG laser applications were used in 39% of sites. Mean follow-up was 23 months and no significant complications were seen. CONCLUSION: An L-CRA as a means of permanently bypassing the obstruction to venous outflow in CRVO may become more relevant as not all patients respond well to intravitreal therapy. The limitation to this technique in the past has been lack of availability of a laser system with the power necessary to create the L-CRA. The success rate with the new system has improved to 88% representing a significant improvement over our original success rate of 33%. PMID- 26991652 TI - Presence of hepatitis C (HCV) infection in Baby Boomers with Medicare is independently associated with mortality and resource utilisation. AB - BACKGROUND: Hepatitis C virus is common among Baby Boomers (BB). As this cohort ages, they will increasingly become Medicare eligible. AIM: To evaluate resource utilisation and mortality of BB-Medicare recipients with HCV. METHODS: We used in patient and out-patient Medicare databases (2005-2010). HCV was identified using ICD-9 codes. Outcomes included resource utilisation [payment/case and in-patient length of stay (LOS)] and short-term mortality. RESULTS: Of 1 153 862 BB Medicare recipients (2005-2010), 3.2% (N = 37 365) had HCV. During this period, in-patient Medicare-BB (39 793-55 235) and their claims (78 924-106 232) increased. Furthermore, their overall mortality increased from 8.94% to 10.25% (P < 0.0001). In multivariate analysis, HCV [OR = 1.23 (1.16-1.29)], older age [OR = 1.98 (1.82 2.14)], male gender [OR = 1.25 (1.22-1.29)], ESRD [OR = 1.31 (1.26-1.36)], Charlson score [OR = 1.41 (1.40-1.42)] and LOS [OR = 1.02 (1.02-1.02)] predicted mortality. LOS decreased from 12.98 to 11.74 days (P < 0.0001), whereas total payments increased from $22 157 to $23 185 (P < .0001). During the study, the number of out-patient Medicare BB patients (123 097-192 110) and claims (863 978 1 340 260) also increased. Furthermore, overall mortality increased from 3.15% to 3.31% (P = 0.0131). Again, HCV [OR = 1.23 (1.16-1.30)], older age [OR = 2.03 (1.89-2.17)], ESRD [OR = 3.40 (3.28-3.51)], disabled status [OR = 1.49 (1.40 1.58)] and Charlson score [OR = 1.39 (1.38-1.40)] predicted mortality. Annual total out-patient payments increased from $3781 to $4001 (P < 0.0001). HCV [36.04% [34.28-37.82%)], 45-49 age [4.21% (3.14-5.28%)], ESRD [966.31% (954.86 977.88%)], disabled status [43.22% (41.67-44.80%)], Charlson score [46.78% (46.31 47.26%)] and study year [2.72% (2.58-2.85%)] independently predicted increases in payments. CONCLUSIONS: In Baby Boomer Medicare recipients, diagnosis of HCV is independently associated with higher mortality and resource utilisation. PMID- 26991651 TI - Decentralization of Acid Fast Bacilli (AFB) External Quality Assurance Using Blind Rechecking for Sputum Smear Microscopy in Ethiopia. AB - INTRODUCTION: Ethiopia achieved a rapid expansion of TB microscopic centers for acid fast bacilli (AFB). However, external quality assurance (EQA) services were, until recently, limited to few regional and sub-regional laboratories. In this paper, we describe the decentralization experience and the result of EQA using random blinded rechecking. MATERIALS AND METHODS: The routine EQA quarterly report was compiled and analyzed. A positive result by the microscopic center while the EQA center reported negative result is categorized as false positive (FP). A negative result by the microscopic center while the EQA center reported positive is considered false negative (FN). The reading of EQA centers was considered a gold standard to compute the sensitivity, specificity, positive predictive (PPV) and negative predictive values (NPV) of the readings of microscopic centers. RESULTS: We decentralized sputum smear AFB EQA from 4 Regional Laboratories (RRLs) to 82 EQA centers and enrolled 956 health facilities in EQA schemes. Enrollment of HFs in EQA was gradual because it required training and mentoring laboratory professionals, institutionalizing internal QA measures, equipping all HFs to perform diagnosis, and establishing more EQA centers. From 2012 to 2014 (Phase I), the FP rate declined from 0.6% to 0.2% and FN fell from as high as 7.6% to 1.6% in supported health facilities (HFs). In HFs that joined in Phase II, FN rates ranged from 5.6 to 7.3%. The proportion of HFs without errors has increased from 77.9% to 90.5% in Phase I HFs and from 82.9% to 86.9% in Phase II HFs. Overall sensitivity and specificity were 95.0% and 99.7%, respectively. PPV and NPV were 93.3% and 99.7%, respectively. CONCLUSION: Decentralizing blinded rechecking of sputum smear microscopy is feasible in low income settings. While a comprehensive laboratory improvement strategy enhanced the quality of microscopy, laboratory professionals' capacity in slide reading and smear quality requires continued support. PMID- 26991653 TI - Low-Density Water Structure Observed in a Nanosegregated Cryoprotectant Solution at Low Temperatures from 285 to 238 K. AB - The structure of liquid water is defined by its molecular association through hydrogen bonding. Two different structures have been proposed for liquid water at low temperatures: low-density liquid (LDL) and high-density liquid (HDL) water. Here, we demonstrate a platform that can be exploited to experimentally probe the structure of liquid water in equilibrium at temperatures down to 238 K. We make use of a cryoprotectant molecule, glycerol, that, when mixed with water, lowers the freezing temperature of the solution nonmonotonically with glycerol concentration. We use a combination of neutron diffraction measurements and computational modeling to examine the structure of water in glycerol-water liquid mixtures at low temperatures from 285 to 238 K. We confirm that the mixtures are nanosegregated into regions of glycerol-rich and water-rich clusters. We examine the water structure and reveal that, at the temperatures studied here, water forms a low-density water structure that is more tetrahedral than the structure at room temperature. We postulate that nanosegregation allows water to form a low density structure that is protected by an extensive and encapsulating glycerol interface. PMID- 26991654 TI - Subcutaneous immunoglobulin for treatment of multifocal motor neuropathy. AB - INTRODUCTION: Subcutaneous immunoglobulin (SCIg) has been used for treatment of immune neuropathies. METHODS: We evaluated the safety and efficacy of 1.53:1 SCIg to intravenous immunoglobulin (IVIg) in individuals receiving <2 g/kg IVIg per month and 1:1 in individuals receiving 2 g/kg per month for treatment of multifocal motor neuropathy (MMN) in an open-label, 6-month trial. Medical Research Council sum score, grip strength, modified Guy's Upper Limb Neurological Disability score, Health Utility Index Quality of Life score, and immunoglobulin levels were evaluated at baseline and at 3 and 6 months. RESULTS: Eleven men and 4 women, aged 31-82 years, were enrolled. Eleven patients completed the program with minor localized reactions and high satisfaction. Three of 6 patients receiving less than 1.53:1 replacement developed intolerable weakness by month 3, and 1 exited after developing erythema and elevated transaminase levels. CONCLUSION: Patients with MMN tolerate SCIg infusion with maintained strength, but some patients may develop increasing weakness and merit close monitoring. Muscle Nerve 54: 856-863, 2016. PMID- 26991656 TI - Mineralocorticoid Receptor Antagonism: A Promising Therapeutic Approach to Treat Ischemic AKI. AB - Acute kidney injury (AKI) is a common complication in hospitalized patients. One of the leading causes of AKI is renal ischemia/reperfusion (IR). In spite of all the progress made in acquiring knowledge about the mechanisms involved in AKI, no pharmacologic approach has yet become successful in clinical trials. Recent evidence suggests that mineralocorticoid receptor (MR) antagonism may be a useful strategy to prevent or treat AKI induced by IR. Here, we summarize the experimental work that supports MR antagonism as a potential approach to treat this disease. We also review the evidence that identifies a critical mechanism participating in the sustained vasoconstriction during kidney IR and uncovers that this mechanism is targeted by MR antagonists, thus explaining their beneficial effects. PMID- 26991655 TI - Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer. AB - Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer. PMID- 26991657 TI - Childhood Household Dysfunction, Social Inequality and Alcohol Related Illness in Young Adulthood. A Swedish National Cohort Study. AB - The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973 82 (n = 872,912), which was followed from age 18 to 29-40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7 2.5], two CHD indicators 5.6 [4.4-7.1], three or more indicators 9.4 [7.1-12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks-those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9-14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4-1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage. PMID- 26991658 TI - Adapting to the Changing Climate: An Assessment of Local Health Department Preparations for Climate Change-Related Health Threats, 2008-2012. AB - BACKGROUND: Climate change poses a major public health threat. A survey of U.S. local health department directors in 2008 found widespread recognition of the threat, but limited adaptive capacity, due to perceived lack of expertise and other resources. METHODS: We assessed changes between 2008 and 2012 in local public health departments' preparedness for the public health threats of climate change, in light of increasing national polarization on the issue, and widespread funding cutbacks for public health. A geographically representative online survey of directors of local public health departments was conducted in 2011-2012 (N = 174; response rate = 50%), and compared to the 2008 telephone survey results (N = 133; response rate = 61%). RESULTS: Significant polarization had occurred: more respondents in 2012 were certain that the threat of local climate change impacts does/does not exist, and fewer were unsure. Roughly 10% said it is not a threat, compared to 1% in 2008. Adaptation capacity decreased in several areas: perceived departmental expertise in climate change risk assessment; departmental prioritization of adaptation; and the number of adaptation-related programs and services departments provided. In 2008, directors' perceptions of local impacts predicted the number of adaptation-related programs and services their departments offered, but in 2012, funding predicted programming and directors' impact perceptions did not. This suggests that budgets were constraining directors' ability to respond to local climate change-related health threats. Results also suggest that departmental expertise may mitigate funding constraints. Strategies for overcoming these obstacles to local public health departments' preparations for climate change are discussed. PMID- 26991659 TI - When the right (Drug) should be left: Prenatal drug exposure and heterotaxy syndrome. AB - BACKGROUND: Recent studies reported an association between prenatal propylthiouracil exposure and birth defects, including abnormal arrangement across the left-right body axis, suggesting an association with heterotaxy syndrome. METHODS: This case-control and case-finding study used data from 1981 to 2013 from the EUROCAT birth defect registry in the Northern Netherlands. First, we explored prenatal exposures in heterotaxy syndrome (cases) and Down syndrome (controls). Second, we describe the specific birth defects in offspring of mothers using propylthiouracil (PTU) prenatally. RESULTS: A total of 66 cases with heterotaxy syndrome (incidence 12.1 per 100,000 pregnancies) and 783 controls with Down syndrome (143.3 per 100,000 pregnancies) were studied. No differences in intoxication use during pregnancy were found between cases and controls, including smoking (28.0% vs. 22.7%; p = 0.40), alcohol (14.0% vs. 26.9%; p = 0.052), and recreational drugs (0 vs. 0.3%; p = 1.00). We found an association between heterotaxy syndrome and prenatal drug exposure to follitropin alfa (5.6% vs. 1.1%; p = 0.04), and drugs used in nicotine dependence (3.7% vs. 0.2%; p = 0.02). Five mothers used PTU during pregnancy and gave birth to a child with trisomy 18, renal abnormalities, or hypospadias and cardiac defects. CONCLUSION: This study identified follitropin-alfa and drugs used in nicotine dependence as possible teratogens of heterotaxy syndrome. Our data suggest the possibility that there is an increased risk of birth defects (including renal, urological, and cardiac abnormalities) in children born among mothers taking PTU prenatally, but not for heterotaxy syndrome. Birth Defects Research (Part A) 106:573-579, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991661 TI - Genetics Series. PMID- 26991660 TI - Medication-assisted treatment for hospitalized patients with intravenous-drug-use related infective endocarditis. AB - BACKGROUND AND OBJECTIVES: A feared complication of opioid use disorder (OUD) is intravenous drug use related infective endocarditis (IDU-IE). We report on our experience engaging hospitalized IDU-IE patients to initiate medication-assisted treatment (MAT). METHODS: A retrospective study (n = 29) using descriptive statistics. RESULTS: Overall, 9 (31.0%) successfully initiated buprenorphine maintenance during the hospitalization, and 9 (31.0%) accepted a referral to methadone maintenance following discharge. Eleven (37.9%) declined MAT altogether. DISCUSSION AND CONCLUSIONS: Hospitalizations may represent an important opportunity to engage IDU-IE patients to initiate MAT. SCIENTIFIC SIGNIFICANCE: The study provides preliminary support of engaging hospitalized IDU IE patients to initiate MAT. PMID- 26991663 TI - The Zika Pandemic - A Perfect Storm? PMID- 26991662 TI - Availability of Amino Acids Extends Chronological Lifespan by Suppressing Hyper Acidification of the Environment in Saccharomyces cerevisiae. AB - The chronological lifespan of Saccharomyces cerevisiae represents the duration of cell survival in the postdiauxic and stationary phases. Using a prototrophic strain derived from the standard auxotrophic laboratory strain BY4742, we showed that supplementation of non-essential amino acids to a synthetic defined (SD) medium increases maximal cell growth and extends the chronological lifespan. The positive effects of amino acids can be reproduced by modulating the medium pH, indicating that amino acids contribute to chronological longevity in a cell extrinsic manner by alleviating medium acidification. In addition, we showed that the amino acid-mediated effects on extension of chronological longevity are independent of those achieved through a reduction in the TORC1 pathway, which is mediated in a cell-intrinsic manner. Since previous studies showed that extracellular acidification causes mitochondrial dysfunction and leads to cell death, our results provide a path to premature chronological aging caused by differences in available nitrogen sources. Moreover, acidification of culture medium is generally associated with culture duration and cell density; thus, further studies are required on cell physiology of auxotrophic yeast strains during the stationary phase because an insufficient supply of essential amino acids may cause alterations in environmental conditions. PMID- 26991664 TI - Home behavioral economics: Childcare decisions in the United States and Norway. AB - This research investigated how a couple decides which parent stays home as a childcare provider by attempting to determine the economic value on maternal care versus paternal care while examining the potential effects of nationality, gender role attitudes, and social support. We collected data from 240 American participants and 250 Norwegian participants who were asked to decide how much a mother needs to earn to allow her husband to stay at home to provide childcare and how much a father needs to earn to allow his wife to stay at home and provide childcare, in addition to items assessing gender role attitudes. No effect of social support was found, but Norwegians were slightly more likely than Americans to place a heavier earning burden on the husband. There were few differences in gender role attitudes by nationality. The impact of public policy and social desirability on the results and childcare decision making are discussed. PMID- 26991665 TI - Altitudinal and climatic associations of seed dormancy and flowering traits evidence adaptation of annual life cycle timing in Arabidopsis thaliana. AB - The temporal control or timing of the life cycle of annual plants is presumed to provide adaptive strategies to escape harsh environments for survival and reproduction. This is mainly determined by the timing of germination, which is controlled by the level of seed dormancy, and of flowering initiation. However, the environmental factors driving the evolution of plant life cycles remain largely unknown. To address this question we have analysed nine quantitative life history traits, in a native regional collection of 300 wild accessions of Arabidopsis thaliana. Seed dormancy and flowering time were negatively correlated, indicating that these traits have coevolved. In addition, environmental-phenotypic analyses detected strong altitudinal and climatic clines for most life history traits. Overall, accessions showing life cycles with early flowering, small seeds, high seed dormancy and slow germination rate were associated with locations exposed to high temperature, low summer precipitation and high radiation. Furthermore, we analysed the expression level of the positive regulator of seed dormancy DELAY OF GERMINATION 1 (DOG1), finding similar but weaker altitudinal and climatic patterns than seed dormancy. Therefore, DOG1 regulatory mutations are likely to provide a quantitative molecular mechanism for the adaptation of A. thaliana life cycle to altitude and climate. PMID- 26991666 TI - One-Pot Synthesis of Benzothiazole-Tethered Chromanones/Coumarins via Claisen Rearrangement Using the Solid State Melt Reaction. AB - A novel protocol has been successfully established for the efficient synthesis of benzothiazole-tethered chromanone/coumarin scaffolds via Claisen rearrangement using a solid state melt reaction in a one-pot manner. Benzothiazole formation and Claisen rearrangement involve the cleavage of S-S and C-O bonds and formation of C-S, C?N, and C-C bonds in a single operation without using a catalyst or solvent. PMID- 26991667 TI - Electroencephalographic study showing that tactile stimulation by fabrics of different qualities elicit graded event-related potentials. AB - BACKGROUND/PURPOSE: Neurophysiologic data on reactions of the human brain towards tactile stimuli evoked by fabrics moved on the skin are scarce. Furthermore, evaluation of fabrics' pleasantness using questionnaires suffers subjective biases. That is why we used a 64-channel electroencephalography (EEG) to objectively evaluate real-time brain reactions to fabric-skin interactions. METHODS: Tactile stimuli were triggered by selected fabrics of different qualities, i.e. modal/polyamide single jersey, cotton double rib and a jute fabric, applied hidden to either the palm or forearm of 24 subjects via a custom made fabric-to-skin applicator called SOFIA. One-way anova analysis was carried out to verify the EEG data. RESULTS: The modal/polyamide fabric applied to the forearm and palm led to slightly stronger emotional valence scores in the brain than the conventional or baseline fabric. Furthermore, the single jersey elicits significant higher event-related potential (ERP) signals in all subjects when applied to the forearm, suggesting less distraction and better cognitive resources during the fabric/skin interaction. The brain thus reacts with instantaneous ERP to tactile stimulation of fabrics and is able to discriminate different qualities via implicit preferences. CONCLUSION: The test procedure described here may be a tool to evaluate the fabric feel with the exclusion of subjective biases. PMID- 26991668 TI - Spicy Adjectives and Nominal Donkeys: Capturing Semantic Deviance Using Compositionality in Distributional Spaces. AB - Sophisticated senator and legislative onion. Whether or not you have ever heard of these things, we all have some intuition that one of them makes much less sense than the other. In this paper, we introduce a large dataset of human judgments about novel adjective-noun phrases. We use these data to test an approach to semantic deviance based on phrase representations derived with compositional distributional semantic methods, that is, methods that derive word meanings from contextual information, and approximate phrase meanings by combining word meanings. We present several simple measures extracted from distributional representations of words and phrases, and we show that they have a significant impact on predicting the acceptability of novel adjective-noun phrases even when a number of alternative measures classically employed in studies of compound processing and bigram plausibility are taken into account. Our results show that the extent to which an attributive adjective alters the distributional representation of the noun is the most significant factor in modeling the distinction between acceptable and deviant phrases. Our study extends current applications of compositional distributional semantic methods to linguistically and cognitively interesting problems, and it offers a new, quantitatively precise approach to the challenge of predicting when humans will find novel linguistic expressions acceptable and when they will not. PMID- 26991669 TI - Evaluating a Midwife-Led Model of Antenatal Care for Women with a Previous Cesarean Section: A Retrospective, Comparative Cohort Study. AB - BACKGROUND: Research is yet to identify effective and safe interventions to increase the vaginal birth after cesarean (VBAC) rate. This research aimed to compare intended and actual VBAC rates before and after implementation of midwife led antenatal care for women with one previous cesarean birth and no other risk factors in a large, tertiary maternity hospital in England. METHODS: This was a retrospective, comparative cohort study. Data were collected from the medical records of women with one previous lower segment cesarean delivery and no other obstetric, medical, or psychological complications who gave birth at the hospital before (2008) and after (2011) the implementation of midwife-led antenatal care. Chi-squared analysis was used to calculate the odds ratio, and logistic regression to account for confounders. RESULTS: Intended and actual VBAC rates were higher in 2011 compared with 2008: 90 percent vs. 77 percent, adjusted odds ratio (aOR) 2.69 (1.48-4.87); and 61 percent vs. 47 percent, aOR 1.79 (1.17 2.75), respectively. Mean rates of unscheduled antenatal care sought via the delivery suite and inpatient admissions were lower in 2011 than 2008. Postnatal maternal and neonatal safety outcomes were similar between the two groups, except mean postnatal length of stay, which was shorter in 2011 compared with 2008 (2.67 vs. 3.15 days). CONCLUSIONS: Implementation of midwife-led antenatal care for women with one previous cesarean offers a safe and effective alternative to traditional obstetrician-led antenatal care, and is associated with increased rates of intended and actual VBAC. PMID- 26991670 TI - Photoinduced Gilch Polymerization: A Basically New Access to Poly(p-phenylene vinylenes) (PPVs) of Exciting Constitutional Homogeneity. AB - A novel procedure has been developed for the Gilch reaction leading to poly(p phenylene vinylenes) (PPVs). In the first step, selective activation of the starting material is achieved at low temperature. Subsequently, controlled chain growth is induced by lighting the alpha-halo-p-quinodimethane monomer. In contrast to the thermal Gilch polymerization, the photoinduced process allows adjusting crucial parameters such as intensity and energy of light. The progress of PPV formation can be followed visually or by in situ UV-vis spectroscopy. If the polymers are formed under appropriate conditions, they show very high molar masses, polydispersities in the common range, and higher constitutional homogeneity than thermally grown PPVs. PMID- 26991671 TI - Tidal volume measurements in infants: Opto-electronic plethysmography versus pneumotachograph. AB - Tidal breathing measurements by Opto-Electronic Plethysmography (OEP) has been reported for infants limited to protocols with two chest wall compartments. Standard protocol for the analysis of adults, with three compartments of chest wall, has been unavailable for analysis of infants. We aimed to study the agreement of simultaneous measurements of tidal volume by OEP (VT,OEP ) and a heated pneumotachograph (PNT) (VT,PNT ) performed during sleeping in 20 infants (gestational age 35.1 +/- 4.6 weeks) at 3-4 months postconceptual age with a three compartment protocol. From PNT and OEP measurements, tidal volume corrected (VT,PNT ) for ambient conditions were calculated with a total number of 200 breaths. The two methods were in good agreement with tidal volume mean difference of 0.02 ml and limit of agreement -4.11 to 4.08 ml (95%CI), no relationship was found between differences and means of OEP and PNT measurements. Pulmonary rib cage, abdominal rib cage and abdomen contributed by 12.4 +/- 9.7%, 5.2 +/- 5.1%, and 82.4 +/- 11.4% to VT,OEP , respectively. The OEP experimental protocol based on 52 markers and a three-compartment model of the chest wall could be used in spontaneously sleeping infants. Pediatr Pulmonol. 2016;51:850-857. (c) 2016 Wiley Periodicals, Inc. PMID- 26991672 TI - Stable Blue Phosphorescence Iridium(III) Cyclometalated Complexes Prompted by Intramolecular Hydrogen Bond in Ancillary Ligand. AB - Improvement of the stability of blue phosphorescent dopant material is one of the key factors for real application of organic light-emitting diodes (OLEDs). In this study, we found that the intramolecular hydrogen bonding in an ancillary ligand from a heteroleptic Ir(III) complex can play an important role in the stability of blue phosphorescence. To rationalize the role of intramolecular hydrogen bonding, a series of Ir(III) complexes is designed and prepared: Ir(dfppy)2(pic-OH) (1a), Ir(dfppy)2(pic-OMe) (1b), Ir(ppy)2(pic-OH) (2a), and Ir(ppy)2(pic-OMe) (2b). The emission lifetime of Ir(dfppy)2(pic-OH) (1a) (tauem = 3.19 MUs) in dichloromethane solution was found to be significantly longer than that of Ir(dfppy)2(pic-OMe) (1b) (tauem = 0.94 MUs), because of a substantial difference in the nonradiative decay rate (knr = 0.28 * 10(5) s(-1) for (1a) vs 2.99 * 10(5) s(-1) for (1b)). These results were attributed to the intramolecular OH...O?C hydrogen bond of the 3-hydroxy-picolinato ligand. Finally, device lifetime was significantly improved when 1a was used as the dopant compared to FIrpic, a well-known blue dopant. Device III (1a as dopant) achieved an operational lifetime of 34.3 h for an initial luminance of 400 nits compared to that of device IV (FIrpic as dopant), a value of 20.1 h, indicating that the intramolecular hydrogen bond in ancillary ligand is playing an important role in device stability. PMID- 26991674 TI - The transition to self-regulated learning for first-year dental students: threshold concepts. AB - Research shows that when students arrive at university they are often not prepared for independent learning. New students enter a period of transition during their first year, which is often characterised by emotional destabilisation, as they move towards becoming more self-regulating in their new learning environment. In this small-scale qualitative study, data from an in depth pair interview were triangulated with data from a questionnaire, to explore participants' experiences of self-regulated learning in the first year of a Dental Surgery course. Five threshold concepts relating to learning in transition emerged from the analysis of the data. These concepts were as follows: learning how to learn using a range of self-chosen sources instead of a single textbook, learning how to organise incoming information without guidance, distinguishing between main ideas and detail during revision, coping with a heavy workload, and knowing what to expect from examinations and coursework. Strong emotions (feeling confused, overwhelmed and scared) were associated with negotiating these threshold concepts. However, the study illustrates how the participants adopted new cognitive and metacognitive strategies to become more self-regulating over time. The findings of the study suggest that lecturers, tutors, study advisers and peers all have an important role to play in explicitly guiding first-year students as they grapple with troublesome threshold concepts relating to self regulated learning. Furthermore, structural changes to the content-heavy, lecture based curricula often associated with first-year Medical and Dental courses would help ease students' transition to independent learning, which may make an impact on student attainment. PMID- 26991673 TI - Twenty-five years of prescription opioid use in Australia: a whole-of-population analysis using pharmaceutical claims. AB - AIM: The aim of this paper is to investigate 25-year trends in community use of prescribed opioid analgesics in Australia, and to map these trends against major changes to opioid registration and subsidy. METHODS: We obtained dispensing data from 1990 to 2014 from two sources: dispensing claims processed under Australia's national drug subsidy programme, the Pharmaceutical Benefits Scheme, including under co-payment records from 2012; and estimates of non-subsidized medicine use from a survey of Australian pharmacies (until 2011). Utilization was expressed in defined daily doses (DDD)/1000 population/day. RESULTS: Opioid dispensing increased almost four-fold between 1990 and 2014, from 4.6 to 17.4 DDD/1000 pop/day. In 1990, weak, short-acting or orally administered opioids accounted for over 90% of utilization. Use of long-acting opioids increased over 17-fold between 1990 and 2000, due primarily to the subsidy of long-acting morphine and increased use of methadone for pain management. Between 2000 and 2011, oxycodone, fentanyl, buprenorphine, tramadol and hydromorphone use increased markedly. Use of strong opioids, long-acting and transdermal preparations also increased, largely following the subsidy of various opioids for noncancer pain. In 2011, the most dispensed opioids were codeine (41.1% of total opioid use), oxycodone (19.7%) and tramadol (16.1%); long-acting formulations comprised approximately half, and strong opioids 40%, of opioid dispensing. CONCLUSIONS: Opioid utilization in Australia is increasing, although these figures remain below levels reported in the US and Canada. The increased use of opioids was largely driven by the subsidy of long-acting formulations and opioids for the treatment of noncancer pain. PMID- 26991675 TI - Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes. AB - BACKGROUND: Gluten-free (GF) diet alleviates type 1 diabetes in animal models and possibly in humans. We recently showed that fatty acid-induced insulin secretion is enhanced by enzymatically digested gluten (gliadin) stimulation in INS-1E insulinoma cells. We therefore hypothesized that GF diet would induce beta-cell rest and ameliorate type 2 diabetes. METHODS: C57BL/6JBomTac (B6) mice were fed a high-fat (HF), gluten-free high-fat (GF-HF), standard (STD) or gluten-free (GF) diet for 42 weeks. RESULTS: Short-term (6-24 weeks) GF-HF versus HF feeding impaired glucose tolerance and increased fasting glucose. Long-term (36-42 weeks) GF-HF versus HF feeding improved glucose tolerance and decreased fasting leptin. Mice fed a GF-HF versus HF diet for 42 weeks showed higher volumes of beta cells, islets and pancreas. The beta-cell volume correlated with the islet- and pancreas volume as well as body weight. GF-HF versus HF diet did not influence toll-like receptor 4 (Tlr4), interleukin 1 (IL-1), interleukin 6 (IL-6) or tumour necrosis factor-alpha (TNF-alpha) mRNA expression in intestine. STD versus GF feeding did not affect any parameter studied. CONCLUSIONS: Long-term feeding with GF-HF versus HF increases beta-cell volume and improves glucose tolerance in B6 mice. The mechanism may include beta-cell rest, but is unlikely to include TLR4 and proinflammatory cytokines in the intestine. Beta-cell volume correlates with pancreas volume and body weight, indicating that insulin secretion capacity controls pancreas volume. Thus, long-term GF diets may be beneficial for obese type 2 diabetes patients and trials should be performed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991676 TI - Association between histone hyperacetylation status in memory T lymphocytes and allergen-induced eosinophilic airway inflammation. AB - BACKGROUND AND OBJECTIVE: T lymphocytes, which are characterized by longevity and immune memory, play an important role in airway inflammation in asthma. Here, we assessed the association between immune memory and histone deacetylation and/or acetylation status. METHODS: CD4 + CD45RB(low) cells (memory T (Tm)) obtained from the spleens of asthma mice models were co-cultured with glucocorticoids (GCs), trichostatin A (TSA) or anacardic acid (AA) and adoptively transferred to naive mice. Interleukin (IL)-4, 5 and 13 and IFN-gamma concentrations were measured in culture supernatants and bronchoalveolar lavage fluid (BALF). Histone deacetylase (HDAC) and histone acetyltransferase (HAT) activities and the expression of T-bet, GATA-3, HDACs 1-11 and alveolar eosinophilic inflammation index (AEII) were determined in lung tissues. RESULTS: Culture supernatants and the BALF showed similar cytokine profiles. AA and GCs significantly inhibited HAT activity (P = 0.002 and P = 0.018), whereas TSA inhibited and GCs promoted HDAC activity (P = 0.004 and P = 0.025). HDACs 7, 9 and 10 were upregulated by AA and GCs (all P < 0.032), while HDAC11 was upregulated by GCs (P = 0.028). GC-induced inhibition of Tm histone acetylation alleviated AEII by downregulating IL-4, 5 and 13, similar to the effect of AA. CONCLUSION: Histone hyperacetylation status induced by low expression of HDACs 7, 9 and 10 in allergen-specific Tm cells contributes to eosinophilic airway inflammation. The mechanism by which GCs improve airway inflammation involves the upregulation of HDACs 7, 9, 10 and 11 and especially HDAC-10. The role of individual HDACs and AA as novel therapeutic agents for allergic asthma needs to be explored in the future. PMID- 26991678 TI - Using intron sequence comparisons in the triose-phosphate isomerase gene to study the divergence of the fall armyworm host strains. AB - The noctuid moth Spodoptera frugiperda (the fall armyworm) is endemic to the Western Hemisphere and appears to be undergoing sympatric speciation to produce two subpopulations that differ in their choice of host plants. The 'rice strain' and 'corn strain' are morphologically indistinguishable, requiring the use of genetic markers for identification. Because fall armyworm is a major pest of corn and several other agricultural crops, characterizing the strains has important economic consequences. In this study, comparisons were made of the intron sequences from the triose-phosphate isomerase (Tpi) gene isolated from 85 fall armyworm specimens collected from two host plants. Sixteen new strain-specific haplotypes based on intron polymorphisms are described that can facilitate the characterization of fall armyworm populations associated with different host plants. Comparisons of genetic diversity within and between the strains provides evidence that the corn strain is undergoing active selection and supports the proposal of directional interstrain mating occurring in the wild. Comparisons of the polymorphisms indicate that each intron undergoes different patterns of mutation that in some cases corresponds to host plant preferences. The results confirm that intron sequence comparisons are an effective approach to study fall armyworm population genetics. PMID- 26991677 TI - Effect of topical neuromodulatory medications on oral and skin keratinocytes. AB - BACKGROUND: Neuromodulatory medications (NMs), such as amitriptyline, carbamazepine and gabapentin, are used as topical preparations for the management of neuropathic orofacial pain (NOP) and have produced promising preliminary results. The aim of this study was to investigate the effects of three aforementioned NMs on cell lines relevant to the orofacial tissues in vitro as no published studies have examined the effect of these topical NMs. METHODS: Cellular viability was measured using alamarBlue(r) , testing cumulative and specific time point effects of NMs on human skin keratinocytes and oral keratinocytes. Effects of the NMs on cell counts were investigated by CCK-8 assay. Drug concentrations released from NM orabase pastes after 30-min incubation were measured by high-performance liquid chromatography. Using these clinical concentrations, morphological changes and cytokine expression were investigated using scanning electron microscopy (SEM) and human inflammatory antibody array (AAH), respectively. RESULTS: Cumulative and specific time point viability and cell count methods revealed that amitriptyline caused a significant decrease in cellular viability and counts in both cell lines. Carbamazepine also had significant effects after long-term exposure and at higher concentrations, whilst gabapentin had little demonstrable effect. SEM confirmed the cytotoxicity of amitriptyline, whilst AAH revealed no significant changes in cytokine expression following amitriptyline, carbamazepine or gabapentin exposure compared with control. CONCLUSIONS: The results raise concerns about the safety of topical amitriptyline as it was cytotoxic to skin and oral keratinocytes in both exposure times and concentrations, whilst carbamazepine was cytotoxic only at high concentrations and after longer exposure times and gabapentin had no demonstrable effects. PMID- 26991679 TI - Optically Active Hybrid Materials Constructed from Helically Substituted Polyacetylenes. AB - Functional materials derived from synthetic helical polymers are attracting increasing interest. Helically substituted polyacetylenes (HSPAs) are especially interesting as typical artificial helical polymers. In recent years, we designed and prepared a series of functional materials based on HSPAs and inorganic materials. The target is to establish some novel hybrid materials that combine the superior properties of both. The examined inorganic materials include silica, graphene, and magnetic Fe3 O4 nanoparticles. Such new functional materials hold great promise and are expected to find practical applications, for instance, as chiral absorbents, chiral sensors, chiral selectors for inducing enantioselective crystallization, chiral catalysts towards asymmetric catalysis, and chiral carriers for enantioselective release. The Personal Account summarizes our major achievements in preparing optically active hybrid materials. We hope it will speed up progress in chiral-related research areas. PMID- 26991681 TI - Monoclonal antibodies safety and occupational hazard: Current practice in Australia. PMID- 26991680 TI - In vivo detection of 2-hydroxyglutarate in brain tumors by optimized point resolved spectroscopy (PRESS) at 7T. AB - PURPOSE: To test the efficacy of 7T MRS for in vivo detection of 2 hydroxyglutarate (2HG) in brain tumors. METHODS: The subecho times of point resolved spectroscopy (PRESS) were optimized at 7T with density-matrix simulations and phantom validation to improve the 2HG signal selectivity with respect to the neighboring resonances of gamma-aminobutyric acid (GABA), glutamate (Glu), and glutamine (Gln). MRS data were acquired from 12 subjects with gliomas in vivo and analyzed with LCModel using calculated basis spectra. Metabolite levels were quantified using unsuppressed short echo time (TE) water as a reference. RESULTS: The PRESS TE was optimized as TE = 78 ms (TE1 = 58 ms and TE2 = 20 ms), at which the 2HG 2.25 ppm resonance appeared as a temporally maximum inverted narrow peak and the GABA, Glu, and Gln resonances between 2.2 and 2.5 ppm were all positive peaks. The PRESS TE = 78 ms method offered improved discrimination of 2HG from Glu, Gln, and GABA when compared with short-TE MRS. 2HG was detected in all patients enrolled in the study, the estimated 2HG concentrations ranging from 1.0 to 6.2 mM, with percentage standard deviation of 2%-7%. CONCLUSION: Data indicate that the optimized MRS provides good selectivity of 2HG from other metabolite signals and may confer reliable in vivo detection of 2HG at relatively low concentrations. Magn Reson Med 77:936-944, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26991682 TI - Commentary: Patients as Partners: Building on the Experience of Outcome Measures in Rheumatology. PMID- 26991683 TI - Nurse and patient characteristics predict communication about complementary and alternative medicine. AB - BACKGROUND: The aim of this study was to identify nurse factors (eg, knowledge, practices, and clinical habits regarding complementary and alternative medicine [CAM] as well as demographic factors) and patient characteristics (eg, age, sex, and treatment status) associated with nurses' CAM inquiry and referral patterns. METHODS: Baseline data were collected with nurse/patient questionnaires about CAM use and knowledge as part of a multicenter CAM educational clinical trial. Frequencies and nested regression models were used to assess predictors of nurses' inquiries about and referral to CAM therapies. RESULTS: Six hundred ninety-nine patients participated in the study. For patients, female sex (odds ratio [OR], 1.50; P = .019) and cancer recurrence (OR, 1.45; P = .05) were predictive of nurses' inquiries about and referral to CAM therapies. A total of 175 nurses with a mean age of 45 years and a mean experience of 20 years participated; 79% were staff nurses, and 11% were nurse practitioners. Fifty three percent asked at least 1 of their last 5 patients about CAM use; 42% referred patients to CAM therapy. Nurses who reported being "somewhat comfortable" (OR, 2.70; P = .0001) or "very comfortable" (OR, 3.88; P < .0001) about discussing CAM, self-reported use of massage (OR, 2.20; P < .0001), and had formal CAM education (OR, 4.14; P = .0001) were more likely to ask about CAM use. Nurses who reported being "somewhat comfortable" (OR, 2.54; 95% confidence interval, 1.47-4.41; P = .0008) or "very comfortable" (OR, 7.46; P < .00001) and had formal CAM education (OR, 2.96; P < .0001) were also more likely to refer patients to CAM therapies. CONCLUSIONS: Both patient and nurse characteristics were associated with discussions about CAM. Oncology institutions that prioritize evidence-based medicine should consider introducing CAM education to their nursing staff. Cancer 2016;122:1552-9. (c) 2016 American Cancer Society. PMID- 26991684 TI - Tailored treatment strategies: a new approach for modern management of atrial fibrillation. AB - Atrial fibrillation (AF) is not benign. Cardiovascular diseases and risk factors differ importantly amongst patients. Careful phenotyping with the aim to start tailored therapy may improve outcome and quality of life. Furthermore, structural remodelling plays an important role in initiation and progression of AF. Therapies that interfere in the remodelling processes are promising because they may modify the atrial substrate. However, success is still limited probably due to variations in the underlying substrate in individual patients. The most favourable effects of lifestyle changes on success of rhythm control have been demonstrated in obese patients with AF. Differences in genotype may also play an important role. Common gene variants have been associated with recurrence of AF after electrical cardioversion, antiarrhythmic drug therapy and catheter ablation. Therefore, both phenotyping and genotyping may become useful for patient selection in the future. Beside the choice of rate or rhythm control, and type of rhythm control, prevention of complications associated with AF may also differ depending on genotype and phenotype. Efficacy of stroke prevention has been well established, but bleeding remains a clinically relevant problem. Risk stratification is still cumbersome, especially in low-risk patients and in those with a high bleeding risk. The decision whether to start anticoagulation (and if so which type of anticoagulant) or, alternatively, to implant an occlusion device of the left atrial appendage may also be improved by genotyping and phenotyping. In this review, we will summarize new insights into the roles of phenotype and genotype in generating more tailored treatment strategies in patients with AF and discuss several patient-tailored treatment options. PMID- 26991685 TI - Nurses' caring and empathy in Jordanian psychiatric hospitals: A national survey. AB - Nurses working in psychiatric hospitals need to acquire the skills of therapeutic communication and empathy, and have higher levels of caring. The present study aims to investigate the level of caring and empathy among nurses working in psychiatric hospitals. A cross-sectional survey was utilized to collect data from 205 nurses recruited from three psychiatric hospitals in Jordan. The Background Information Questionnaire, Modified Caring Dimensions Inventory, and Toronto Empathy Questionnaire were administered to the recruited participants. The findings revealed that the sampled nurses had a high level of caring and empathy. Significant correlations were found between caring and having a specialized training in mental health nursing, and having organizational and managerial support. However, no significant correlations were found between empathy and participants' characteristics. Specialized training in mental health nursing, having organizational and managerial support, and empathy were found predictors for caring. PMID- 26991686 TI - Urine testing to monitor the impact of HPV vaccination in Bhutan and Rwanda. AB - Bhutan (2010) and Rwanda (2011) were the first countries in Asia and Africa to introduce national, primarily school-based, human papillomavirus (HPV) vaccination programmes. These target 12 year-old girls and initially included catch-up campaigns (13-18 year-olds in Bhutan and ninth school grade in Rwanda). In 2013, to obtain the earliest indicators of vaccine effectiveness, we performed two school-based HPV urine surveys; 973 female students (median age: 19 years, 5th-95th percentile: 18-22) were recruited in Bhutan and 912 (19 years, 17-20) in Rwanda. Participants self-collected a first-void urine sample using a validated protocol. HPV prevalence was obtained using two PCR assays that differ in sensitivity and type spectrum, namely GP5+/GP6+ and E7-MPG. 92% students in Bhutan and 43% in Rwanda reported to have been vaccinated (median vaccination age = 16, 5th-95th: 14-18). HPV positivity in urine was significantly associated with sexual activity measures. In Rwanda, HPV6/11/16/18 prevalence was lower in vaccinated than in unvaccinated students (prevalence ratio, PR = 0.12, 95% confidence interval, CI: 0.03-0.51 by GP5+/GP6+, and 0.45, CI: 0.23-0.90 by E7 MPG). For E7-MPG, cross-protection against 10 high-risk types phylogenetically related to HPV16 or 18 was of borderline significance (PR = 0.68; 95% CI: 0.45 1.01). In Bhutan, HPV6/11/16/18 prevalence by GP5+/GP6+ was lower in vaccinated than in unvaccinated students but CIs were broad. In conclusion, our study supports the feasibility of urine surveys to monitor HPV vaccination and quantifies the effectiveness of the quadrivalent vaccine in women vaccinated after pre-adolescence. Future similar surveys should detect increases in vaccine effectiveness if vaccination of 12 year-olds continues. PMID- 26991687 TI - Hemoadsorption in Infection-Associated Rhabdomyolysis. PMID- 26991688 TI - Lorcaserin Use in the Management of Morbid Obesity in a Pre-Liver Transplant Patient. AB - Management of obesity and decompensated cirrhosis in those requiring liver transplantation (LT) is a challenging dilemma. Because of concerns for perioperative complications, many centers avoid transplant in those with a body mass index (BMI) greater than 40 kg/m(2) . Bariatric surgery is associated with increased risk attributable to complications of portal hypertension, including variceal rupture. Therefore, weight loss and LT options are limited. Several new classes of weight loss drugs are commercially available, including the anoretic, lorcaserin. This case illustrates the successful use of lorcaserin in a morbidly obese individual with decompensated cirrhosis evaluated for LT listing. (Hepatology 2016;64:301-302). PMID- 26991689 TI - Cellular effects of acute exposure to high peak power microwave systems: Morphology and toxicology. AB - Electric fields produced by advanced pulsed microwave transmitter technology now readily exceed the Institute of Electrical and Electronic Engineers (IEEE) C.95.1 peak E-field limit of 100 kV/m, highlighting a need for scientific validation of such a specific limit. Toward this goal, we exposed Jurkat Clone E-6 human lymphocyte preparations to 20 high peak power microwave (HPPM) pulses (120 ns duration) with a mean peak amplitude of 2.3 MV/m and standard deviation of 0.1 with the electric field at cells predicted to range from 0.46 to 2.7 MV/m, well in excess of current standard limit. We observed that membrane integrity and cell morphology remained unchanged 4 h after exposure and cell survival 24 h after exposure was not statistically different from sham exposure or control samples. Using flow cytometry to analyze membrane disruption and morphological changes per exposed cell, no changes were observed in HPPM-exposed samples. Current IEEE C95.1-2005 standards for pulsed radiofrequency exposure limits peak electric field to 100 kV/m for pulses shorter than 100 ms [IEEE (1995) PC95.1-Standard for Safety Levels with Respect to Human Exposure to Electric, Magnetic and Electromagnetic Fields, 0 Hz to 300 GHz, Institute of Electrical and Electronic Engineers: Piscataway, NJ, USA]. This may impose large exclusion zones that limit HPPM technology use. In this study, we offer evidence that maximum permissible exposure of 100 kV/m for peak electric field may be unnecessarily restrictive for HPPM devices. Bioelectromagnetics. 37:141-151, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991690 TI - Cellular cannibalism in giant cells of central giant cell granuloma of jaw bones and giant cell tumors of long bones. AB - AIM: The aim of the present study was to investigate the relationship of central giant cell granuloma (CGCG) and giant cell tumor of long bones (GCT) with respect to cannibalistic giant cells (GCs). METHOD: Sixteen cases each of CGCG and GCT were histopathologically analyzed for cannibalistic GCs. One hundred GCs were examined in each section, and the number of cannibalistic GCs was expressed in percentage. RESULTS: Cannibalistic GCs were seen in all cases of CGCG and GCT (100%). GCT showed significantly higher mean cannibalistic GC frequency (44.81 +/ 1.013) than CGCG (32.06 +/- 1.398), aggressive CGCG (38.17 +/- 1.579), non aggressive CGCG (28.40 +/- 0.6360), non-recurrent CGCG (30.42 +/- 1.417), and recurrent CGCG (37.00 +/- 2.483). In aggressive CGCG, the mean cannibalistic GC frequency was significantly higher (38.17 +/- 1.579) than the non-aggressive variant (28.40 +/- 0.6360). Recurrent CGCG cases showed significantly higher mean cannibalistic GC frequency (37.00 +/- 2.483) than non-recurrent cases (30.42 +/- 1.417). Similarly, recurrent GCT showed significantly higher mean cannibalistic GC frequency (47.4 +/- 4.97) than non-recurrent GCT (43.63 +/- 3.1). CONCLUSION: The distinctness of CGCG and GCT was observed in terms of mean cannibalistic GC count. The assessment of cannibalistic GC in CGCG and GCT could help in predicting the biological behavior and grading of the tumor. PMID- 26991691 TI - Association between serum 25-hydroxyvitamin D and serum sex steroid hormones among men in NHANES. AB - BACKGROUND: Recent literature suggests that high circulating vitamin D may increase prostate cancer risk. Although the mechanism through which vitamin D may increase risk is unknown, vitamin D concentration could influence circulating sex steroid hormones that may be associated with prostate cancer; an alternate explanation is that it could be associated with prostate-specific antigen (PSA) concentration causing detection bias. OBJECTIVE: We examined whether serum vitamin D concentration was associated with sex steroid hormone and PSA concentrations in a cross-sectional analysis of men in the National Health and Nutrition Examination Surveys (NHANES). DESIGN: Testosterone, oestradiol, sex hormone-binding globulin (SHBG), androstanediol glucuronide, and 25 hydroxyvitamin D (25(OH)D) were measured in serum from men aged 20 and older participating in NHANES III (n = 1315) and NHANES 2001-2004 (n = 318). Hormone concentrations were compared across 25(OH)D quintiles, adjusting for age, race/ethnicity, body fat percentage, and smoking. PSA concentration was estimated by 25(OH)D quintile in 4013 men from NHANES 2001-2006. RESULTS: In NHANES III, higher testosterone (quintile (Q) 1 = 17.2, 95% confidence interval (CI) = 16.1 18.6; Q5 = 19.6, 95% CI = 18.7-20.6 nmol/l, P-trend = 0.0002) and SHBG (Q1 = 33.8, 95% CI = 30.8-37.0; Q5 = 38.4, 95% CI = 35.8-41.2 nmol/l, P-trend = 0.0005) were observed with increasing 25(OH)D. Similar results were observed in NHANES 2001-2004. PSA concentration was not associated with serum 25(OH)D (P-trend = 0.34). CONCLUSION: Results from these nationally representative studies support a positive association between serum 25(OH)D and testosterone and SHBG. The findings support an indirect mechanism through which vitamin D may increase prostate cancer risk, and suggest the link to prostate cancer is not due to PSA detection bias. PMID- 26991692 TI - A20 deficiency leads to angiogenesis of pulmonary artery endothelial cells through stronger NF-kappaB activation under hypoxia. AB - A20 is a zinc finger protein associated with hypoxia. As chronic hypoxia is responsible for intimal hyperplasia and disordered angiogenesis of pulmonary artery, which are histological hallmarks of pulmonary artery hypertension, we intended to explore the role of A20 in angiogenesis of pulmonary artery endothelial cells (ECs). Here, we found a transient elevation of A20 expression in the lung tissues from hypoxic rats compared with normoxic controls. This rapid enhancement was mainly detected in the endothelium, and similar results were reproduced in vitro. During early hypoxia, genetic inhibition of A20 increased proliferation in pulmonary artery ECs, linking to advanced cell cycle progression as well as microtubule polymerization, and aggravated angiogenic effects including tube formation, cell migration and adhesion molecules expression. In addition, a negative feedback loop between nuclear factor-kappa B and A20 was confirmed. Our findings provide evidence for an adaptive role of A20 against pulmonary artery ECs angiogenesis via nuclear factor-kappa B activation. PMID- 26991693 TI - Chemical constituents and their antibacterial activity from the tropical endophytic fungus Diaporthe sp. F2934. AB - AIMS: To isolate, characterize and determine the antibacterial activities of compounds produced by the endophytic fungus Diaporthe sp. F2934, cultivated on malt extract agar. METHODS AND RESULTS: The fungus was cultivated aseptically in Petri dishes containing malt extract agar at 25 degrees C for 15 days. Crude extract was obtained from mycelium using ethyl acetate and sonication, and was fractioned using classic chromatography and HPLC. The structures of phomosines and chromanones were established by NMR experiments including HMQC, HMBC and COSY. Their molecular formulas were determined by ESI-TOFMS. We obtained six compounds: (1) 4H-1-benzopyra-4-one-2,3-dihydro-5-hydroxy-2,8-dimetyl, (2) 4H-1 benzopyran-4-one-2,3-dihydro-5-hydroxy-8-(hydroxylmethyl)-2-methyl, (3) 4H-1 benzopyra-4-one-2,3-dihydro-5-methoxyl-2,8-dimetyl, (4) phomosine A, (5) phomosine D and (6) phomosine C. Isolated compounds 1, 2 and 5 were inactive against 15 micro-organisms, but phomosines A and C were active against diverse Gram-negative and Gram-positive bacteria. CONCLUSIONS: A group of new chromanones and known phomosines have been isolated from the genus Diaporthe (Diaporthe sp. F2934). The results obtained confirm the wide chemical diversity produced by endophytic fungi, specifically the genus Diaporthe. In addition, phomosines A and C may be considered as antimicrobial agents that can be used to guide the development of new antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Our phylogenetic analysis places Diaporthe sp. F2934 as sister to the Diaporthe cynaroidis clade. Three chromanones were isolated and identified, for the first time, using crude extract obtained from Diaporthe F2934. From this extract phomosines A, C and D were also purified. Regarding Staphylococcus aureus, the inhibition zone diameter (IZD) for phomosine A was 20% higher than the standard drug, vancomycin. When cultivated as described here, Diaporthe sp. F2934 produced new and antimicrobial compounds. PMID- 26991694 TI - The prevalence and validity of high, biologically implausible values of weight, height, and BMI among 8.8 million children. AB - OBJECTIVE: This study assessed the prevalence and consistency of high values of weight, height, and BMI considered to be biologically implausible (BIV) using cut points proposed by WHO among 8.8 million low-income children (13.7 million observations). METHODS: Cross-sectional and longitudinal analyses were performed among 2- to 4-year-olds who were examined from 2008 through 2011. RESULTS: Overall, 2.7% of the body size measurements were classified as BIVs; 95% of these BIVs were very high. Among the subset of children (3.6 million) examined more than once, most of those who initially had a high weight or BMI BIV also had a high BIV at the second examination; odds ratios were >250. Based on several alternative classifications of BIVs, the current cut points likely underestimate the prevalence of obesity by about 1%. CONCLUSIONS: Many of the extremely high values of body size currently flagged as BIVs are unlikely to be errors. Increasing the z-score cut points or using a percentage of the maximum values in the National Health and Nutrition Examination Survey, could improve the balance between removing probable errors and retaining those that are likely correct. PMID- 26991695 TI - Seasonal neuronal plasticity in song-control and auditory forebrain areas in subtropical nonmigratory and palearctic-indian migratory male songbirds. AB - This study examines whether differences in annual life-history states (LHSs) among the inhabitants of two latitudes would have an impact on the neuronal plasticity of the song-control system in songbirds. At the times of equinoxes and solstices during the year (n = 4 per year) corresponding to different LHSs, we measured the volumetric changes and expression of doublecortin (DCX; an endogenous marker of the neuronal recruitment) in the song-control nuclei and higher order auditory forebrain regions of the subtropical resident Indian weaverbirds (Ploceus philippinus) and Palearctic-Indian migratory redheaded buntings (Emberiza bruniceps). Area X in basal ganglia, lateral magnocellular nucleus of the anterior nidopallium (LMAN), HVC (proper name), and robust nucleus of the arcopallium (RA) were enlarged during the breeding LHS. Both round and fusiform DCX-immunoreactive (DCX-ir) cells were found in area X and HVC but not in LMAN or RA, with a significant seasonal difference. Also, as shown by increase in volume and by dense, round DCX-ir cells, the neuronal incorporation was increased in HVC alone during the breeding LHS. This suggests differences in the response of song-control nuclei to photoperiod-induced changes in LHSs. Furthermore, DCX immunoreactivity indicated participation of the cortical caudomedial nidopallium and caudomedial mesopallium in the song-control system, albeit with differences between the weaverbirds and the buntings. Overall, these results show seasonal neuronal plasticity in the song-control system closely associated with annual reproductive LHS in both of the songbirds. Differences between species probably account for the differences in the photoperiod-response system between the relative refractory weaverbirds and absolute refractory redheaded buntings. J. Comp. Neurol. 524:2914-2929, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991696 TI - Synthesis of Octafluoroporphyrin. AB - Despite the long list of known fluoroporphyrinoids, the most fundamental 2,3,7,8,12,13,17,18-octafluoroporphyrin (OFP) has not been synthesized until now. It is achieved by condensation of two molecules of tetrafluoro-dipyrrylmethane-2 carboxaldehyde in the presence of magnesium(II) salts. The fluorinated dipyrrylmethane also gives 5,15-bis(pentafluorophenyl)-OFP (F18P) with a reasonable yield. Both Mg/OFP and Zn/F18P in the solid-state reveal an essentially flat structure. The fluoro groups impart as much as a 0.5 V anodic shift for porphyrin ring oxidation/reduction, as well as hypsochromic shifts in the Uv-vis spectra. PMID- 26991697 TI - Tpd3-Pph21 phosphatase plays a direct role in Sep7 dephosphorylation in Candida albicans. AB - Septins are a component of the cytoskeleton and play important roles in diverse cellular processes including cell cycle control, cytokinesis and polarized growth. In fungi, septin organization, dynamics and function are regulated by phosphorylation, and several kinases responsible for the phosphorylation of several septins have been identified. However, little is known about the phosphatases that dephosphorylate septins. Here, we report the characterization of Tpd3, a structural subunit of the PP2A family of phosphatases, in the pathogenic fungus Candida albicans. We found that tpd3Delta/Delta cells are defective in hyphal growth and grow as pseudohyphae under yeast growth conditions with aberrant septin organization. Western blotting detected hyperphosphorylation of the septin Sep7 in cells lacking Tpd3. Tpd3 and Sep7 colocalize at the bud neck and can coimmunoprecipitate. Furthermore, we discovered similar defects in cells lacking Pph21, a catalytic subunit of the PP2A family, and its physical association with Tpd3. Importantly, purified Tpd3-Pph21 complexes can dephosphorylate Sep7 in vitro. Together, our findings strongly support the idea that the Tpd3-Pph21 complex dephosphorylates Sep7 and regulates morphogenesis and cytokinesis. The tpd3Delta/Delta mutant is greatly reduced in virulence in mice, providing a potential antifungal target. PMID- 26991700 TI - Graphical Representation for Heterogeneous Face Recognition. AB - Heterogeneous face recognition (HFR) refers to matching face images acquired from different sources (i.e., different sensors or different wavelengths) for identification. HFR plays an important role in both biometrics research and industry. In spite of promising progresses achieved in recent years, HFR is still a challenging problem due to the difficulty to represent two heterogeneous images in a homogeneous manner. Existing HFR methods either represent an image ignoring the spatial information, or rely on a transformation procedure which complicates the recognition task. Considering these problems, we propose a novel graphical representation based HFR method (G-HFR) in this paper. Markov networks are employed to represent heterogeneous image patches separately, which takes the spatial compatibility between neighboring image patches into consideration. A coupled representation similarity metric (CRSM) is designed to measure the similarity between obtained graphical representations. Extensive experiments conducted on multiple HFR scenarios (viewed sketch, forensic sketch, near infrared image, and thermal infrared image) show that the proposed method outperforms state-of-the-art methods. PMID- 26991698 TI - Effect of Knee Extensor Strength on Incident Radiographic and Symptomatic Knee Osteoarthritis in Individuals With Meniscal Pathology: Data From the Multicenter Osteoarthritis Study. AB - OBJECTIVE: High knee extensor strength may be important to protect against the development of knee osteoarthritis (OA) in populations at elevated risk, such as individuals with meniscal pathology. We investigated the extent to which high knee extensor muscle strength was associated with a decreased risk of developing radiographic or symptomatic knee OA in individuals with medial meniscal pathology. METHODS: We studied knees that at the baseline visit of the Multicenter Osteoarthritis Study had medial meniscal pathology but did not have radiographic knee OA (373 knees in 373 participants) or symptomatic knee OA (combination of radiographic knee OA and frequent knee symptoms; 531 knees in 531 participants). Isokinetic knee extensor strength was measured at baseline, and participants were followed for development of incident radiographic knee OA or incident symptomatic knee OA at 84 months. Separate binomial regression analyses with robust SEs adjusted for age, history of knee surgery, physical activity level, and clinic site were conducted for men and women. RESULTS: High knee extensor strength (normalized by allometric scaling) was associated with a reduced risk of radiographic knee OA in women (relative risk [RR] 0.52, 95% confidence interval [95% CI] 0.29-0.94) but not in men (RR 0.56, 95% CI 0.27 1.16). High knee extensor strength did not protect against the development of symptomatic knee OA, either in women or men. CONCLUSION: The results only partly confirm the hypothesis that high knee extensor muscle strength protects against later development of knee OA in individuals with medial meniscal pathology. PMID- 26991701 TI - 2016: Creating a Culture of Safety in Oncology. AB - Nurses play vital roles in preventing errors and improving the quality of care for patients. However, in the breakthrough Institute of Medicine (IOM) reports, To Err Is Human: Building a Safer Health System (IOM, 1999) and Crossing the Quality Chasm: A New Health System for the 21st Century (IOM, 2001), it was estimated that about 44,000-98,000 Americans die each year as a result of medical errors. Gibson and Singh's (2003) book, Wall of Silence: The Untold Story of the Medical Mistakes That Kill and Injure Millions of Americans, shared real-life stories of medical mistakes to help raise awareness and create a sense of urgency for the issues surrounding healthcare errors. Gibson and Singh (2003) also included aspects of the human side of errors-the perceptions of the healthcare providers regarding their errors and the responses of patients who had been harmed. ?. PMID- 26991699 TI - TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors. AB - Although most sporadic colorectal cancers (CRC) are thought to develop from protruded adenomas through the adenoma-carcinoma sequence, some CRC develop through flat lesions, so-called laterally spreading tumors (LST). We previously analyzed epigenetic aberrations in LST and found that LST are clearly classified into two molecular subtypes: intermediate-methylation with KRAS mutation and low methylation with absence of oncogene mutation. Intermediate-methylation LST were mostly granular type LST (LST-G) and low-methylation LST were mostly non-granular LST (LST-NG). In the present study, we conducted a targeted exon sequencing study including 38 candidate CRC driver genes to gain insight into how these genes modulate the development of LST. We identified a mean of 11.5 suspected nonpolymorphic variants per sample, including indels and non-synonymous mutations, although there was no significant difference in the frequency of total mutations between LST-G and LST-NG. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P = 0.004), especially KRAS mutation occurring at 70% (30/43) of LST-G but 26% (13/50) of LST-NG (P < 0.0001). Both LST showed high frequency of APC mutation, even at adenoma stage, suggesting its involvement in the initiation stage of LST, as it is involved at early stage of colorectal carcinogenesis via adenoma-carcinoma sequence. TP53 mutation was never observed in adenomas, but was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST NG, but during development of cancer with submucosal invasion in LST-G. It is suggested that TP53 mutation occurs in the early stages of cancer development from adenoma in both LST-G and LST-NG, but is involved at an earlier stage in LST NG. PMID- 26991702 TI - When the Patient Seeks Cure: Challenging Chemotherapy and Radiation Side Effects Requiring Creative Solutions. AB - When undergoing concomitant chemotherapy and radiation therapy for anal cancer, patients often experience significant side effects, including grade 1 or 2 radiation dermatitis, pain, exudate, and diarrhea. This case study presents a grade 3 reaction complicated by complex medical conditions. In addition to an evidence-based skin care treatment and side effect management plan that support patients during this intense period, this article offers creative strategies to provide a cost-effective healing option. PMID- 26991703 TI - Oral Chemotherapy Education: Using Innovation to Ensure Broad Access. AB - The purpose of this article is to share one institution's intervention to improve oral chemotherapy patient education. The overall aim was to provide clinicians with a single source of educational materials that would meet a diverse group of patients' educational needs and be consistent with published guidelines.?. PMID- 26991704 TI - Weight Management and Exercise for Cancer Survivors. AB - Obesity may contribute to development and recurrence of cancer, as well as cancer related and all-cause mortality. This risk factor is also among the most preventable causes of cancer. This article describes current evidence-based guidelines for weight management and physical activity for cancer survivors. The authors also discuss practical interventions to help survivors undertake behavioral changes to manage their weight. PMID- 26991705 TI - New Positron-Emission Tomography/Computed Tomography Imaging for Bone Metastases?. AB - With the increase in new therapies to treat cancer, improved diagnostic tools are needed to help determine best treatment options. Many radiopharmaceuticals used with positron-emission tomography/computed tomography have been tested to evaluate solid cancers. Two of the newer radiopharmaceuticals are 18F sodium fluoride and radiolabeled choline. This article reviews these new technologies, providing background and potential clinical use. PMID- 26991706 TI - Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part II. AB - Chemotherapy desensitization protocols are safe, but labor-intensive, processes that allow patients with cancer to receive medications even if they initially experienced severe hypersensitivity reactions. Part I of this column discussed the pathophysiology of hypersensitivity reactions and described the development of desensitization protocols in oncology settings. Part II incorporates the experiences of an academic medical center and provides a practical guide for the nursing care of patients undergoing chemotherapy desensitization.?. PMID- 26991707 TI - Instruments for Assessing Chemotherapy-Induced Peripheral Neuropathy: A Review of the Literature. AB - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and often dose-limiting side effect of chemotherapy that can result in disability and poorer quality of life. However, no standardized measurement for CIPN exists. Clinicians often base decisions for dose modification or discontinuation of a chemotherapeutic agent on patient report of subjective symptoms and physical examination. OBJECTIVES: This review is designed to identify valid and reliable assessment tools that measure or assess CIPN in adult patients receiving chemotherapy. METHODS: A systematic literature review was conducted using PubMed, CINAHL(r), and Cochrane Library. Articles were included if their primary purpose was to evaluate the psychometric properties of scales to measure CIPN in adult patients with cancer receiving neurotoxic chemotherapeutic agents. FINDINGS: The search yielded 143 results, with 16 articles meeting criteria for inclusion in the review. Seven unique scales and their reduced and modified versions were examined. The majority of the questionnaires were evaluated in a single tumor type, primarily with taxanes and platinum compounds. No consensus exists on the most appropriate patient self-report scale for use in the general oncology population. PMID- 26991708 TI - Stress Levels of Nurses in Oncology Outpatient Units. AB - BACKGROUND: Oncology nursing is often a source of substantial stress for nurses. Many nurses, particularly novice nurses, have inadequate preparation to care for patients at the end of life and their families. Unless nurses prevent or manage work-related stress by using effective coping strategies, oncology nursing staff will continue to suffer from burnout and compassion fatigue. OBJECTIVES: The purpose of this article is to identify stress levels and stressful factors of nurses working in oncology outpatient units and to explore coping behaviors for work-related stress of oncology staff nurses in outpatient units. METHODS: A descriptive, cross-sectional design was used to identify stress levels and stressful factors for outpatient oncology nurses, investigate differences in stress levels among nurses' demographic characteristics, and explore coping behaviors of the nurses. Study participants (N = 40) included RNs and licensed practical nurses who completed the Nursing Stress Scale, three open-ended questions, and a demographic questionnaire. FINDINGS: The highest sources of stress were workload and patient death and dying. Demographic variables of age and work experience in nursing showed a significant positive relationship to work related stress scores. The three most frequently used coping behaviors were verbalizing, exercising or relaxing, and taking time for self. Continuing education programs on stress management are highly recommended. Outpatient oncology nurses should be nurtured and supported through tailored interventions at multiple levels to help them find effective coping strategies and develop self care competencies. Although younger and less experienced nurses had lower mean stress scores than older and more experienced nurses, the continuing education programs and tailored interventions would be helpful for all oncology nursing staff. PMID- 26991709 TI - Blinatumomab: A New Treatment for Adults With Relapsed Acute Lymphocytic Leukemia. AB - BACKGROUND: Patients with acute lymphocytic leukemia (ALL) often experience relapse of their disease following standard treatment. Blinatumomab (Blincyto(r)) is a newly approved option for inducing remission in individuals with relapsed or refractory Philadelphia chromosome-negative B-cell ALL. OBJECTIVES: This article provides an overview of blinatumomab, its benefits demonstrated in clinical trials, adverse effects, administration details, and the role of the oncology nurse in caring for and educating patients who receive blinatumomab. METHODS: This article summarizes the results of two phase II studies on blinatumomab and provides practice implications for nurses caring for patients receiving this therapy. FINDINGS: Attentive symptom monitoring and management are crucial. Individuals who achieve remission from blinatumomab can then be considered for stem cell transplantation and a chance for cure. PMID- 26991710 TI - Caregiver Burden in End-Stage Ovarian Cancer. AB - BACKGROUND: Caregiver burden associated with caring for women with ovarian cancer has received limited focus. However, these patients often have complex needs, requiring a high level of care at home and imposing substantial burdens on caregivers. OBJECTIVES: This pilot study assessed the level of caregiver burden experienced by the primary caregivers of patients with end-stage ovarian cancer and identified variables associated with caregiver burden. METHODS: Caregiver burden was assessed using the Caregiver Reaction Assessment. Fifty caregivers completed an anonymous and voluntary survey. Pearson correlations and independent samples t tests were used to analyze data. FINDINGS: Most participants were Caucasian, married or living with a partner, and college graduates, with an annual household income of less than $90,000. Caregiver ages ranged from 29-81 years. Participants agreed most with the self-esteem scale, indicating they had pride in caring for their loved ones. Disrupted schedules and financial problems were the most burdensome factors in providing care. Because financial issues affected caregiver burden, nurses should facilitate interdisciplinary support. Future research is needed to determine the impact of nurse-led interventions to reduce caregiver burden. PMID- 26991711 TI - A Cross-Sectional Study of Patients' Satisfaction With Totally Implanted Access Ports. AB - BACKGROUND: Totally implanted access ports (PACs) are valuable tools for the treatment of patients with cancer because they ease the administration of chemotherapy, stem cells, and supportive care by reducing the rate of peripheral vein punctures. OBJECTIVES: The purpose of this study was to evaluate the satisfaction and impairments of activities of daily living of ambulatory patients with PAC systems receiving chemotherapy. METHODS: This cross-sectional, questionnaire-based study evaluated 202 patients with PAC systems in a comprehensive cancer center and cancer rehabilitation center. From November 2012 to August 2013, patients were invited to answer a questionnaire concerning quality of life and satisfaction with their PAC devices. Data regarding PAC related complications were collected retrospectively by searching patients' medical history. FINDINGS: A total of 202 patients with 230 PAC devices were included. Median time from PAC implantation to inclusion in the study was nine months. Surgical complications occurred in some cases, with bleeding and hematoma being the most frequently observed events. Late complications consisted of infections, drug extravasation, PAC malposition, PAC malfunction, and thrombosis. A third of the patients reported that their PAC interfered with activities of daily living. However, most agreed that PAC systems alleviated the burden of chemotherapy administration, and the vast majority said they would choose the implantation of a PAC system for chemotherapy administration again. PMID- 26991712 TI - Evidence-Based Yoga Interventions for Patients With Cancer. AB - BACKGROUND: Introducing patients with cancer to the practice of yoga can be beneficial for coping with the side effects of treatment and the psychological aspects of cancer that are often difficult and distressing for patients. Oncology nurses can learn to use simple yoga techniques for themselves and as interventions with their patients. OBJECTIVES: This article provides details about the development and implementation of a yoga class for patients with cancer and provides details about other ways nurses can integrate yoga into oncology nursing and cancer care. METHODS: Current research literature was reviewed and synthesized to provide support for the use of yoga as an evidence-based nursing intervention. A detailed approach for implementing yoga into professional practice was delineated. FINDINGS: Yoga techniques can be easily integrated into nursing practice and have been shown to be beneficial for patients and nurses. PMID- 26991713 TI - Patient Preference for Instructional Reinforcement Regarding Prevention of Radiation Dermatitis. AB - BACKGROUND: Although patient preference is a core value within the context of patient-centered models of care, little attention has been paid to determining patient preference for instructional media. Nurses have traditionally used verbal face-to-face instruction as the mainstay of patient education, with written materials being used extensively as teaching guides to supplement verbal instruction or for instructional reinforcement. However, advances in technology have made possible the adding of video instruction to nurses' repertoire of instructional media. OBJECTIVES: The purpose of this study was to determine patients' media preferences (verbal, video, written) when receiving instructional reinforcement about self-care needed to prevent radiation dermatitis. METHODS: The current study was conducted as a secondary analysis of data from a process improvement initiative. In the parent study, patients received multimedia education related to skin care to prevent radiation dermatitis. This secondary analysis examined patient preference for verbal, video, or written education reinforcement at treatment weeks 1 and 3. FINDINGS: Results suggest that, when given a choice, verbal and video reinforcement are preferred over written reinforcement. PMID- 26991714 TI - Preventing Tumor Lysis Syndrome: Two Case Studies of Unexpected Outcomes. AB - BACKGROUND: Tumor lysis syndrome (TLS) is a potentially fatal complication in patients with large, rapidly proliferating tumor cell cancers that may occur after chemotherapy. Patients with TLS are complicated to treat and often have an unpredictable trajectory. OBJECTIVES: The purpose of this article is to report two cases with unusual clinical manifestations and unexpected outcomes during cancer treatment and to share best practices for this situation. METHODS: The authors described details from two unusual cases and outlined lessons learned. The authors described a newly developed clinical order set (protocol) to support optimal care for patients at risk for TLS. FINDINGS: Implementing best practices, the order set prompts early identification of TLS risk and provides step-by-step guidance to eliminate or control TLS. PMID- 26991715 TI - Impact of Changes to Breast Cancer Screening Guidelines on Healthcare Providers and Patients. AB - In October 2015, the American Cancer Society (ACS) updated its evidence-based breast cancer screening guidelines for women at average risk for breast cancer. These guidelines introduced significant changes to the age to begin breast cancer screening, as well as the frequency between screenings and duration of screening. Not long afterward, in January 2016, the U.S. Preventive Services Task Force released its updated breast cancer screening guidelines, which differ from those of the ACS. The varying guidelines present challenges for healthcare providers and patients, particularly women aged 40-49 years. PMID- 26991716 TI - The Process of Oncology Nurse Practitioner Patient Navigation: A Pilot Study. AB - Oncology nurse practitioner (ONP) patient navigators may improve clinical outcomes. However, no standard measures of the process of oncology patient navigation or of related clinical outcomes exist, and research in this area is limited. The exploratory pilot study detailed in this article used grounded theory and interviews with three ONPs to define the processes employed by ONP patient navigators in caring for patients with cancer.?. PMID- 26991717 TI - Are You Choosing Wisely in Your Professional Practice? AB - To enhance the value of care provided to Americans, the American Board of Internal Medicine and Consumer Reports launched the Choosing Wisely(r) initiative in 2012. Choosing Wisely educates providers and patients about high-frequency, low-value care practices that can be avoided to decrease cost and increase the value of health care. The Oncology Nursing Society collaborated with the American Academy of Nursing to add the first-ever nursing-focused list to those previously submitted by more than 70 specialty societies.?. PMID- 26991718 TI - Distress Screening Is a Good Beginning. PMID- 26991719 TI - The Dual Rounding Model: Forging Therapeutic Alliances ?in Oncology and Palliative Care. AB - Inpatients with solid tumors at Duke University Hospital in Durham, NC, are cared for in a dynamic integrated care model that incorporates medical oncology and palliative care. This has profound implications for patients, their loved ones, medical and surgical staff, and oncology nurses. As a nurse with less than three years of experience, my participation in a setting that uses the Dual Rounding Model has accelerated my professional and personal development. During a typical shift, I am an oncology nurse, a palliative care nurse, and a hospice nurse.?. PMID- 26991720 TI - Written Information Improves Patient Knowledge About Implanted Ports. AB - BACKGROUND: Implanted ports are frequently used for patients with cancer who require IV chemotherapy. In addition to verbal communication with healthcare providers, patients with cancer may benefit from written information. OBJECTIVES: This pre/post study evaluated the effectiveness of an informational booklet by improving knowledge about ports and assessed the history, need, and preferences for information. METHODS: Patients with cancer who had an implanted port for at least six months were provided with an informational booklet about ports. Knowledge about ports was tested before (T0) and after (T1) patients read the booklet. Information needs and preferred sources of information were also assessed at T0. Patients reported their opinions of the booklet at T1. FINDINGS: The sample included 129 patients; 49% were male, with a mean age of 59 years. Most patients want to receive as much information as possible, preferably before the port is implanted. However, 43% of patients reported they had received little information about ports. After reading the booklet, patients' knowledge, which was measured with a validated seven-item instrument, improved from T0 to T1 (p < 0.001, effect size = 0.689). Oncology nurses, by providing written and verbal information, can increase patients' knowledge about implanted ports and their confidence in caring for their ports. PMID- 26991721 TI - Therapeutic Massage During Chemotherapy and/or Biotherapy Infusions: Patient Perceptions of Pain, Fatigue, Nausea, Anxiety, and Satisfaction. AB - BACKGROUND: Patients with cancer commonly experience disease or treatment side effects, including pain, fatigue, nausea, and anxiety. An expanding body of literature supports the use of therapeutic massage (TM) as an adjunct to conventional therapies to manage these side effects. OBJECTIVES: This article describes patients' perceptions of pain, fatigue, nausea, and anxiety and their overall satisfaction with TM provided concurrently with chemotherapy and/or biotherapy. METHODS: In an academic outpatient comprehensive cancer center, consenting patients were asked to identify massage site preference (hands and/or feet). The licensed massage therapist delivered TM for 20 minutes to patients concurrently receiving chemotherapy and/or biotherapy. Patients rated their pain, fatigue, nausea, and anxiety pre- and post-TM using a Likert-type scale. Qualitative and quantitative data related to patients' perceived value of TM were obtained postintervention. FINDINGS: Participants (N = 58) reported a statistically significant reduction in each of the following variables. PMID- 26991722 TI - Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab. AB - BACKGROUND: In patients with previously untreated chronic lymphocytic leukemia (CLL) and comorbidities, treatment with the glycoengineered, type II anti-CD20 monoclonal antibody obinutuzumab (Gazyva(r)) (GA101) plus chlorambucil (Leukeran(r)) was associated with superior outcomes to rituximab (Rituxan(r)) plus chlorambucil, with a similar safety profile. However, a higher occurrence of infusion-related reactions (IRRs) was reported with obinutuzumab. These reactions typically require additional management. OBJECTIVES: The focus of this article is to provide oncology nurses and physicians with advice for obinutuzumab IRR management based on clinical trial data and nursing experience. METHODS: The authors reviewed the published management strategies for IRRs with obinutuzumab that were identified during the phase III CLL11 trial and an expanded access phase IIb study (ML28979). Practical advice for obinutuzumab IRR management was developed based on available clinical trial information and nursing experience. FINDINGS: IRRs with obinutuzumab are generally manageable. Most IRRs (all grades), and all grade 3-4 IRRs, occurred during the first infusion. Therefore, IRR management could be improved substantially with extra vigilance at this early stage. PMID- 26991723 TI - Diagnosis Disclosure Process in Patients With Malignant Brain Tumors. AB - BACKGROUND: The way to disclose a cancer diagnosis has evolved, and psycho oncology has developed a more prominent place in cancer care. The diagnosis disclosure process was established to improve the overall quality of patient care and the communication about a cancer diagnosis. OBJECTIVES: The aim of this study was to assess the implementation of the disclosure process in a neurosurgical unit. METHODS: This study was conducted prospectively during a one-year period. All patients were diagnosed with malignant brain tumors and received their diagnosis using the disclosure process. The communication between the provider and the patient during diagnosis disclosure was recorded for analysis, and patients completed a satisfaction survey. FINDINGS: Ninety-one patients with a brain tumor diagnosis participated in the study. Twenty-six were unable to complete the satisfaction survey because they were either deceased or close to the end of their lives. In total, 65 questionnaires were sent to patients and their families, and 43 responded. Patients were satisfied with the quality of the disclosure process regarding information given, psychological support, and communication with all healthcare providers. This assessment allowed the authors to better characterize the impact of the disclosure process on the overall care of patients and to measure the effect of the components of the disclosure process on patient satisfaction. PMID- 26991724 TI - Effect of Isometric Hand Grip Exercises on Blood Flow and Placement of IV Catheters for Administration of Chemotherapy. AB - BACKGROUND: Complications may occur in the subcutaneous or subdermal tissues during IV administration of chemotherapy related to blood flow and catheter placement. OBJECTIVES: Daily isometric hand grip exercises were evaluated for their effect on blood flow in the vessels of the nondominant arm before placement of IV catheters and the success rate of IV catheter placement on the first attempt. METHODS: The study focused on patients with non-Hodgkin lymphoma receiving the first and second cycles of chemotherapy. The intervention group performed daily isometric hand grip exercises before chemotherapy with peripheral catheter insertion. The control group performed routine activities only. Blood flow was measured by ultrasound in the brachial artery (BA) and brachial vein (BV) of the nondominant arm before the first (T1) and second (T2) cycles of chemotherapy. FINDINGS: Blood flow slightly increased in the intervention group at T2 compared to T1. In the control group, blood flow decreased in the BA and did not change in the BV at T2 compared to T1. The success rate for first-attempt placement of a peripheral IV catheter was the same for the intervention and control groups. PMID- 26991726 TI - The ability of Hepascore to predict liver fibrosis in chronic liver disease: a meta-analysis. AB - BACKGROUND & AIMS: Hepascore is a serum model that was developed to assess the severity of liver fibrosis. It has been well validated in common causes of chronic liver disease. This study performed a meta-analysis to evaluate the pooled diagnostic performance of Hepascore and to compare it for different aetiologies of chronic liver disease. METHODS: Two reviewers searched electronic databases from October 2005 to September 2015 for studies that evaluated the diagnostic performance of Hepascore for liver fibrosis in chronic liver disease. RESULTS: 21 studies were included. The AUROC was adjusted according to the distribution of fibrosis stages. The mean adjusted AUROC was 0.83 (95% CI, 0.81 0.85) for significant fibrosis, 0.89 (95% CI, 0.85-0.92) for advance fibrosis and 0.93 (95% CI, 0.91-0.95) for cirrhosis. A cut point of 0.50-0.55 achieved a summary sensitivity of 70% and a summary specificity of 79% to predict significant fibrosis. A cut point of 0.50-0.61 had a summary sensitivity of 81% and a summary specificity of 74% to predict advanced fibrosis. A cut point of 0.80-0.84 had a summary sensitivity of 72% and a summary specificity of 0.88% to predict cirrhosis. The accuracy of Hepascore was similar among all disease aetiologies for the prediction of cirrhosis. However, Hepascore had better diagnostic ability for significant and advanced fibrosis in chronic hepatitis C, chronic hepatitis B and alcoholic liver disease than for non-alcoholic fatty liver disease and HIV co-infected viral hepatitis. CONCLUSIONS: Hepascore is a clinically useful measure of liver fibrosis in patients with common causes of chronic liver disease. PMID- 26991725 TI - Elucidation of the interplay between Fe(II), Fe(III), and dopamine with relevance to iron solubilization and reactive oxygen species generation by catecholamines. AB - The non-enzymatically catalyzed oxidation of dopamine (DA) and the resultant formation of powerful oxidants such as the hydroxyl radical ((*) OH) through 'Fenton chemistry' in the presence of iron within dopaminergic neurons are thought to contribute to the damage of cells or even lead to neuronal degenerative diseases such as Parkinson's disease. An understanding of DA oxidation as well as the transformation of the intermediates that are formed in the presence of iron under physiological conditions is critical to understanding the mechanism of DA and iron induced oxidative stress. In this study, the generation of H2 O2 through the autoxidation and iron-catalyzed oxidation of DA, the formation of the dominant complex via the direct reaction with Fe(II) and Fe(III) in both oxygen saturated and deoxygenated conditions and the oxidation of Fe(II) in the presence of DA at physiological pH 7.4 were investigated. The oxidation of DA resulted in the generation of significant amounts of H2 O2 with this process accelerated significantly in the presence of Fe(II) and Fe(III). At high DA:Fe(II) ratios, the results from this study suggest that DA plays a protective role by complexing Fe(II) and preventing it from reacting with the generated H2 O2 . However, the accumulation of H2 O2 may result in cellular damage as high intracellular H2 O2 concentrations will result in the oxidation of remaining Fe(II) mainly through the peroxidation pathway. At low DA:Fe(II) ratios however, it is likely that DA will act as a pro-oxidant by generating H2 O2 which, in the presence of Fe(II), will result in the production of strongly oxidizing (*) OH radicals. Powerful oxidants such as the hydroxyl radical ((*) OH) have previously been thought to be generated through the interplay between dopamine (DA) and iron, contributing to damage to cells and, potentially, leading to neuronal degenerative diseases such as Parkinson's disease. Our results suggest that DA plays a dual role as high DA/Fe(II) ratios prevent Fe(II) from reacting with the generated H2 O2 thereby reducing (*) OH generation, whereas low DA/Fe(II) ratios enhance (*) OH generation as a result of reaction of unbound Fe(II) and H2 O2 produced via both autoxidation and iron-catalyzed oxidation of DA. PMID- 26991728 TI - Cognitive process-based subtypes of developmental coordination disorder (DCD). AB - The purpose of the study was to identify the cognitive subtypes demonstrated by children with developmental coordination disorder (DCD) using the Planning Attention-Simultaneous-Successive Processing (PASS) theory and the Cognitive Assessment System (D-N CAS). Participants were 108 children aged 5- and 6-years old, 54 with DCD and 54 without DCD, all attending typical kindergartens. They were examined on 31 cognitive-motor variables. Hierarchical-agglomerative and iterative partitioning cluster analyses including 9 motor and 7 cognitive variables revealed the following six subtypes: o C1 = children at risk (having considerable difficulty with jumping and minor difficulty with manual dexterity and simultaneous coding); o C2 = children on the mean (all cognitive-motor scores close to the mean); o C3 = free from cognitive-motor problems (all scores above average); o C4 = manual dexterity, planning and simultaneous coding difficulties; o C5 = manual dexterity, dynamic balance, and planning difficulties; o C6 = generalized cognitive-motor dysfunction (all scores considerably below average). It is well known that DCD is a heterogeneous condition. However, whenever cognitive processes were lower than average, cognitive-motor relationship was evident in subgroups C1, C4, C5 and C6. Early identification of task-specific cognitive-motor difficulties may be essential for early educational intervention practices in order to anticipate and improve learning, academic and performing difficulties. PMID- 26991727 TI - Soft neurological signs and prenatal alcohol exposure: a population-based study in remote Australia. AB - AIM: To identify soft neurological signs (SNS) in a population-based study of children living in remote Aboriginal communities in the Fitzroy Valley, Western Australia, born between 2002 and 2003 and explore the relationship between SNS, prenatal alcohol exposure (PAE), and fetal alcohol spectrum disorders (FASD). METHOD: The presence of SNS was assessed using the Quick Neurological Screening Test, 2nd edition (QNST-2), which has a total maximum score of 140. Higher scores indicated more SNS. 'Severe discrepancy' was defined as scores less than or equal to the fifth centile while 'moderate discrepancy' represented scores from the sixth to the 24th centile. Children were assigned FASD diagnoses using modified Canadian FASD diagnostic guidelines. RESULTS: A total of 108 of 134 (80.6%) eligible children (mean age 8y 9mo, SD=6mo, 53% male) were assessed. The median QNST-2 Total Score for all participants was within the normal category (19.0, range 4-66). However, the median QNST-2 Total Score was higher in children with than without (1) PAE (r=0.2, p=0.045) and (2) FASD (r=0.3, p=0.004). Half (8/16) of children scoring 'moderate discrepancy' and all (2/2) children scoring 'severe discrepancy' had at least three domains of central nervous system impairment. INTERPRETATION: SNS were more common in children with PAE or FASD, consistent with the known neurotoxic effect of PAE. The QNST-2 is a useful screen for subtle neurological dysfunction indicating the need for more comprehensive assessment in children with PAE or FASD. PMID- 26991729 TI - Behavioural variability and motor performance: Effect of practice specialization in front crawl swimming. AB - The aim was to examine behavioural variability within and between individuals, especially in a swimming task, to explore how swimmers with various specialty (competitive short distance swimming vs. triathlon) adapt to repetitive events of sub-maximal intensity, controlled in speed but of various distances. Five swimmers and five triathletes randomly performed three variants (with steps of 200, 300 and 400m distances) of a front crawl incremental step test until exhaustion. Multi-camera system was used to collect and analyse eight kinematical and swimming efficiency parameters. Analysis of variance showed significant differences between swimmers and triathletes, with significant individual effect. Cluster analysis put these parameters together to investigate whether each individual used the same pattern(s) and one or several patterns to achieve the task goal. Results exhibited ten patterns for the whole population, with only two behavioural patterns shared between swimmers and triathletes. Swimmers tended to use higher hand velocity and index of coordination than triathletes. Mono stability occurred in swimmers whatever the task constraint showing high stability, while triathletes revealed bi-stability because they switched to another pattern at mid-distance of the task. Finally, our analysis helped to explain and understand effect of specialty and more broadly individual adaptation to task constraint. PMID- 26991730 TI - Indium Oxide as a Superior Catalyst for Methanol Synthesis by CO2 Hydrogenation. AB - Methanol synthesis by CO2 hydrogenation is attractive in view of avoiding the environmental implications associated with the production of the traditional syngas feedstock and mitigating global warming. However, there still is a lack of efficient catalysts for such alternative processes. Herein, we unveil the high activity, 100 % selectivity, and remarkable stability for 1000 h on stream of In2 O3 supported on ZrO2 under industrially relevant conditions. This strongly contrasts to the benchmark Cu-ZnO-Al2 O3 catalyst, which is unselective and experiences rapid deactivation. In-depth characterization of the In2 O3 -based materials points towards a mechanism rooted in the creation and annihilation of oxygen vacancies as active sites, whose amount can be modulated in situ by co feeding CO and boosted through electronic interactions with the zirconia carrier. These results constitute a promising basis for the design of a prospective technology for sustainable methanol production. PMID- 26991732 TI - Reengineering Dialysis: The Role of Palliative Medicine. AB - BACKGROUND: End-stage renal disease is a life-limiting illness associated with significant morbidity. Half of all individuals with end-stage renal disease are unable to participate in decision making at the end of life, which makes advance care planning critical in this population. OBJECTIVE: We sought to determine the feasibility of embedding palliative medicine consultations in the hemodialysis unit during treatment runs and the impact of this intervention on advance care planning and symptom management. DESIGN: Single-center, prospective cohort study. SETTING/SUBJECTS: Adults receiving in-center hemodialysis at a single outpatient unit were eligible. All consultations occurred during the patients' hemodialysis runs between January 1 and June 30, 2012. MEASUREMENT: Medical records were reviewed for documentation of advance directives, resuscitation status, and goals of care discussions before and after palliative medicine intervention. Symptom surveys with the Modified Edmonton Symptom Assessment Scale (validated for end stage renal disease) were performed preintervention and postintervention. RESULTS: Ninety-two patients were eligible; 91 underwent palliative medicine consultation. Symptoms were well controlled at baseline prior to any intervention. After palliative medicine consultation, the prevalence of unknown code status decreased from 23% to 1% and goals of care documentation improved from 3% to 59%. CONCLUSION: Palliative medicine consultation during in-center outpatient hemodialysis was well received by patients and clinical staff. Patients' symptoms were well managed at baseline by the primary nephrology team. The frequency of goals of care documentation and clarification of code status improved significantly. Embedded palliative medicine specialists on the dialysis care team may be effective in improving multidisciplinary patient-centered care for patients with end-stage renal disease. PMID- 26991731 TI - Kinesin-1 inhibits the aggregation of amyloid-beta peptide as detected by fluorescence cross-correlation spectroscopy. AB - Although the exact etiology and pathogenesis of Alzheimer's disease (AD) are still unclear, amyloid-beta (Abeta) generated by the proteolytic processing of amyloid-beta precursor protein (APP) aggregate to form toxic amyloid species. Kinesin-1 is the first identified ATP-dependent axonal transport motor protein that has been proven to affect Abeta generation and deposition. In this paper, we applied dual-color fluorescence cross-correlation spectroscopy (DC-FCCS) to investigate the direct interaction of Abeta with kinesin-1 at the single-molecule fluorescence level in vitro. The results showed that two kinds of enhanced green fluorescent protein (EGFP)-tagged kinesin light-chain subunits of kinesin 1(KLCs), KLC-E and E-KLC inhibited the aggregation of Abeta over a period of time, providing additional insight into the mechanism of axonal transport deficits in AD. PMID- 26991733 TI - A qualitative exploration of intentional nursing round models in the emergency department setting: investigating the barriers to their use and success. AB - AIMS AND OBJECTIVES: This research aimed to investigate the use of intentional rounding within in the emergency department setting through exploration of the staff nurse experience. The focus was its implementation at a large teaching hospital in England. BACKGROUND: Research into the use of intentional rounding in any area of practice is minimal in the UK; however, a broader evidence base comes from America. The majority of this research supports the notion of intentional rounding for improved patient care and outcomes. Research from the UK is generally more contested. There is less literature on using intentional rounding specifically in the emergency department setting. DESIGN: Qualitative methodological approach. METHODS: Semi-structured interviews (n = 5) were completed with staff nurses working within an emergency department. A purposive sampling technique was used for recruitment. The data was then analysed using 'Framework Method of Qualitative Analysis' (Spencer et al. 2014). RESULTS: The findings were categorised into four headings: (1) Improved patient experience, (2) Current unmanageability, (3) Adapting for the emergency department, (4) Benefits on achieving quality indicators and targets. CONCLUSION: The findings show that although staff felt the introduction of intentional rounding techniques could lead to improvements in patient safety and overall care experience, they also identified a range of difficulties and adaptations needed to ensure its success within this acute care environment. RELEVANCE TO CLINICAL PRACTICE: The research offers an insight into the staff's perceptions of using intentional rounding and also explains the practical difficulties faced by the nursing staff with potential suggestions that may help to address these problems. Benefits include more open communication between staff and patients and potentially more timely response to patient need, which positively impacts levels of safety and satisfaction. Barriers include lack of staff engagement, and the environmental factors and pressures, within the ED setting. PMID- 26991734 TI - Cross-sectional association between physical activity and serum testosterone levels in US men: results from NHANES 1999-2004. AB - Testosterone levels and physical activity each play important roles in men's health, but the relationship between the two remains unclear. We evaluated the cross-sectional association between self-reported total physical activity and serum testosterone levels in 738 men (mean age 42.4 years, range 20->=85 years) who participated in National Health and Nutrition Examination Survey 1999-2004. We compared geometric mean testosterone concentrations measured by radioimmunoassay (RIA) and calculated the odds ratio (OR) of having low or low normal testosterone (<=3.46 ng/mL) across tertiles of total physical activity in all men, and men stratified by age (20-49, >=50 years), and obesity status (BMI < 30, >=30 kg/m(2) ). The geometric mean testosterone concentration was 5.31 ng/mL; 18.6% of the men had low or low normal serum testosterone levels. Physical activity tertiles were not associated with testosterone levels overall, or when stratified by age or obesity status. Similarly, there was no association between physical activity tertiles and the odds of low or low normal testosterone, overall or by age. However, among non-obese men, those in the highest physical activity tertile were significantly less likely to have low or low normal testosterone than those in the lowest tertile (OR 0.50; 95% CI = 0.26-0.95); there was no association among obese men. Greater physical activity was not associated with testosterone levels, but may be associated with a reduced odds of low or low normal testosterone in non-obese men, but not in obese men. PMID- 26991735 TI - Concise Review: The Bystander Effect: Mesenchymal Stem Cell-Mediated Lung Repair. AB - Mesenchymal stem or stromal cells (MSCs), a heterogeneous subset of adult stem/progenitor cells, have surfaced as potential therapeutic units with significant clinical benefit for a wide spectrum of disease conditions, including those affecting the lung. Although MSCs carry both self-renewal and multilineage differentiation abilities, current dogma holds that MSCs mainly contribute to tissue regeneration and repair by modulating the host tissue via secreted cues. Thus, the therapeutic benefit of MSCs is thought to derive from so called bystander effects. The regenerative mechanisms employed by MSCs in the lung include modulation of the immune system as well as promotion of epithelial and endothelial repair. Apart from secreted factors, a number of recent findings suggest that MSCs engage in mitochondrial transfer and shedding of membrane vesicles as a means to enhance tissue repair following injury. Furthermore, it is becoming increasingly clear that MSCs are an integral component of epithelial lung stem cell niches. As such, MSCs play an important role in coupling information from the environment to stem and progenitor populations, such that homeostasis can be ensured even in the face of injury. It is the aim of this review to outline the major mechanisms by which MSCs contribute to lung regeneration, synthesizing recent preclinical findings with data from clinical trials and potential for future therapy. Stem Cells 2016;34:1437-1444. PMID- 26991737 TI - Geography of conservation spending, biodiversity, and culture. AB - We used linear and multivariate models to examine the associations between geography, biodiversity, per capita economic output, national spending on conservation, governance, and cultural traits in 55 countries. Cultural traits and social metrics of modernization correlated positively with national spending on conservation. The global distribution of this spending culture was poorly aligned with the distribution of biodiversity. Specifically, biodiversity was greater in the tropics where cultures tended to spend relatively less on conservation and tended to have higher collectivism, formalized and hierarchical leadership, and weaker governance. Consequently, nations lacking social traits frequently associated with modernization, environmentalism, and conservation spending have the largest component of Earth's biodiversity. This has significant implications for setting policies and priorities for resource management given that biological diversity is rapidly disappearing and cultural traits change slowly. Therefore, we suggest natural resource management adapt to and use characteristics of existing social organization rather than wait for or promote social values associated with conservation spending. Supporting biocultural traditions, engaging leaders to increase conservation commitments, cross-national efforts that complement attributes of cultures, and avoiding interference with nature may work best to conserve nature in collective and hierarchical societies. Spending in modernized nations may be a symbolic response to a symptom of economic development and environmental degradation, and here conservation actions need to ensure that biodiversity is not being lost. PMID- 26991738 TI - Synthesis and separation of cucurbit[n]urils and their derivatives. AB - Cucurbit[n]uril chemistry has become an important part of contemporary supramolecular chemistry since cucurbit[n]urils (Q[n]s) are not only able to encapsulate various guests, but are also capable of coordinating to a wide range of metal ions, leading to the establishment of Q[n]-based host-guest chemistry and coordination chemistry. Each of these impressive developments can be attributed to the growth of protocols for obtaining Q[n]s. In this review, we survey synthetic procedures for obtaining cucurbit[n]urils and their substituted derivatives together with the separation and purification of these remarkable compounds. The coverage is aimed at both existing workers in the field as well as at those requiring an "entry" into Q[n]-based research. PMID- 26991740 TI - Methyl Complexes of the Transition Metals. AB - Organometallic chemistry can be considered as a wide area of knowledge that combines concepts of classic organic chemistry, that is, based essentially on carbon, with molecular inorganic chemistry, especially with coordination compounds. Transition-metal methyl complexes probably represent the simplest and most fundamental way to view how these two major areas of chemistry combine and merge into novel species with intriguing features in terms of reactivity, structure, and bonding. Citing more than 500 bibliographic references, this review aims to offer a concise view of recent advances in the field of transition metal complexes containing M-CH3 fragments. Taking into account the impressive amount of data that are continuously provided by organometallic chemists in this area, this review is mainly focused on results of the last five years. After a panoramic overview on M-CH3 compounds of Groups 3 to 11, which includes the most recent landmark findings in this area, two further sections are dedicated to methyl-bridged complexes and reactivity. PMID- 26991736 TI - Dietary proanthocyanidins inhibit UV radiation-induced skin tumor development through functional activation of the immune system. AB - The incidence of skin cancer is equivalent to the incidence of malignancies in all other organs combined. The main risk factor for this disease is overexposure of the skin to solar ultraviolet (UV) radiation. UV irradiation induces inflammation, oxidative stress, DNA damage, and suppression of the immune system in the skin, which together contribute to carcinogenesis. The use of dietary phytochemicals shows great promise as a complementary and alternative strategy for skin cancer prevention. Grape seed proanthocyanidins (GSPs) have been tested extensively for their anti-skin cancer effect using in vivo animal models. Supplementation of an AIN76A control diet with GSPs (0.2 and 0.5%, w/w) significantly inhibits UV radiation-induced skin tumor development as well as malignant transformation of papillomas to carcinoma in mice. The inhibition of UVB-induced skin tumor development by GSPs is mediated through interrelated mechanisms of action including: (i) inhibition of inflammation, (ii) rapid repair of damaged DNA, and (iii) stimulation of immune system. Additionally, the chemopreventive effects of GSPs involve DNA repair-dependent functional activation of antigen-presenting cells and stimulation of CD8(+) effector T cells. These effects of GSPs could be useful in attenuation of the adverse effects of UV radiation and may have health benefits in humans. PMID- 26991739 TI - Selective Tuberous Sclerosis Complex 1 Gene Deletion in Smooth Muscle Activates Mammalian Target of Rapamycin Signaling and Induces Pulmonary Hypertension. AB - Constitutive activation of the mammalian target of rapamycin (mTOR) complexes mTORC1 and mTORC2 is associated with pulmonary hypertension (PH) and sustained growth of pulmonary artery (PA) smooth muscle cells (SMCs). We investigated whether selective mTORC1 activation in SMCs induced by deleting the negative mTORC1 regulator tuberous sclerosis complex 1 gene (TSC1) was sufficient to produce PH in mice. Mice expressing Cre recombinase under SM22 promoter control were crossed with TSC1(LoxP/LoxP) mice to generate SM22-TSC1(-/-) mice. At 8 weeks of age, SM22-TSC1(-/-) mice exhibited PH with marked increases in distal PA muscularization and Ki67-positive PASMC counts, without systemic hypertension or cardiac dysfunction. Marked activation of the mTORC1 substrates S6 kinase and 4E BP and the mTORC2 substrates p-Akt(Ser473) and glycogen synthase kinase 3 was found in the lungs and pulmonary vessels of SM22-TSC1(-/-) mice when compared with control mice. Treatment with 5 mg/kg rapamycin for 3 weeks to inhibit mTORC1 and mTORC2 fully reversed PH in SM22-TSC1(-/-) mice. In chronically hypoxic mice and SM22-5HTT(+) mice exhibiting PH associated with mTORC1 and mTORC2 activation, PH was maximally attenuated by low-dose rapamycin associated with selective mTORC1 inhibition. Cultured PASMCs from SM22-TSC1(-/-), SM22-5HTT(+), and chronically hypoxic mice exhibited similar sustained growth-rate enhancement and constitutive mTORC1 and mTORC2 activation; both effects were abolished by rapamycin. Deletion of the downstream mTORC1 effectors S6 kinase 1/2 in mice also activated mTOR signaling and induced PH. We concluded that activation of mTORC1 signaling leads to increased PASMC proliferation and subsequent PH development. PMID- 26991741 TI - Prevalence of Vibrio parahaemolyticus in seafood products from hypermarkets in Shanghai. AB - BACKGROUND: Vibrio parahaemolyticus is an important gastroenteritis pathogen contaminating seafood in China. In this study a total of 992 seafood samples from major hypermarkets in Shanghai were monitored for prevalence and burden of V. parahaemolyticus from January 2011 to December 2012. Additionally, appropriate probability distributions for describing V. parahaemolyticus concentrations were assessed based on these surveillance data. RESULTS: Seventeen of 992 samples were positive for V. parahaemolyticus and the geometric mean was 0.1581 most probable number (MPN) g-1 . The variation in prevalence of V. parahaemolyticus was seasonal and the burden of contamination in August (0.1942 MPN g-1 ) was significant (P < 0.01) between 2011 and 2012. Also, the prevalence of V. parahaemolyticus was higher in shellfish and cephalopods than in other seafood (P < 0.05). By comparison, the lognormal distribution and integrated distribution showed no obvious difference for characterizing V. parahaemolyticus contamination. CONCLUSION: The low prevalence and burden found indicated that seafood from hypermarkets may not be an important risk source for V. parahaemolyticus infection in Shanghai, and more attention should be paid to other areas for selling seafood, such as farmlands or farmers' markets. The simple and effective lognormal distribution is recommended as a better choice for describing V. parahaemolyticus contamination in future risk assessment studies. (c) 2016 Society of Chemical Industry. PMID- 26991742 TI - Volvulus in term and preterm infants - clinical presentation and outcome. AB - AIM: Our aim was to assess if term and preterm infants with volvulus showed different patterns with regard to pathogenesis, clinical presentation and outcome. METHODS: We reviewed the medical records and imaging data of infants aged less than six months with volvulus treated in a single surgical referral centre from 2006-2013. RESULTS: Volvulus was diagnosed in 19 infants, with no anatomical anomaly in three of the 12 preterm infants and one of the seven term infants. Most cases (74%) presented during the first eight days of life. Later presentations occurred exclusively in preterm infants, with only one of the five having no anatomic anomalies. Bilious vomiting was the leading symptom in six of the seven term infants, while the symptoms in preterm infants were rather nonspecific. Intestinal necrosis, with the need for bowel resection, occurred in one term (14%) infant and nine (75%) preterm infants. CONCLUSION: The clinical presentation and outcome of volvulus differed between preterm and term infants, but the rate and distribution of underlying anomalies did not differ. Symptoms in preterm infants were often nonspecific and led to a delay in diagnosis. This might have contributed to the higher rate of intestinal necrosis in preterm infants. PMID- 26991743 TI - Polymer-delivered subcutaneous leuprolide acetate formulations achieve and maintain castrate concentrations of testosterone in four open-label studies in patients with advanced prostate cancer. AB - OBJECTIVE: To determine whether luteinising hormone-releasing hormone (LHRH) agonist, ATRIGEL(r) polymer-delivered, subcutaneous, leuprolide acetate (ADSC LA), formulations suppressed serum testosterone to concentrations of <=20 ng/dL. PATIENTS AND METHODS: Data from four open-label, fixed-dose studies were evaluated. Male patients aged 40-86 years with advanced prostatic adenocarcinoma, whom had not undergone prior androgen-deprivation therapy (ADT), were treated with a depot formulation of ADSC-LA: 7.5 mg (1-month, 120 patients), 22.5 mg (3 month, 117 patients), 30 mg (4-month, 90 patients), or 45 mg (6-month, 111 patients). Serum testosterone was sampled at screening, baseline, 2, 4, 8 h after dosing, 1, 2, 3, and 7 days, and every week until the next dose, at which time, the sampling schedule repeated until the end of study (24 weeks for 1- and 3 month formulations, 32 weeks for 4-month, and 48 weeks for the 6-month). The primary analyses were mean serum testosterone concentrations and proportion of patients who achieved concentrations of <=20 ng/dL. RESULTS: The mean (SE) serum testosterone concentrations at the end of study were consistently <=20 ng/dL in each study, at 6.1 (0.4), 10.1 (0.7), 12.4 (0.8), and 12.6 (2.1) ng/dL for the 1 , 3-, 4-, and 6-month formulations, respectively. A high proportion of patients (94%, 90%, 92%, 96% for the 1-, 3-, 4-, and 6-month formulations, respectively) achieved testosterone concentrations of <=20 ng/dL within 6 weeks, and 90-97% of patients in all studies maintained concentrations of <=20 ng/dL from weeks 6-24. CONCLUSIONS: Recent studies have shown improved outcomes in patients with prostate cancer who consistently attained a more rigorous level of testosterone suppression (<=20 ng/dL) with ADT than the historical standard (<=50 ng/dL). All doses of ADSC-LA rapidly achieved and maintained mean serum testosterone to the more rigorous target concentration of <=20 ng/dL. These data suggest that ADSC-LA delivers equivalent testosterone suppression as achieved by surgical castration. PMID- 26991744 TI - l-glutamine Improves Skeletal Muscle Cell Differentiation and Prevents Myotube Atrophy After Cytokine (TNF-alpha) Stress Via Reduced p38 MAPK Signal Transduction. AB - Tumour Necrosis Factor-Alpha (TNF-alpha) is chronically elevated in conditions where skeletal muscle loss occurs. As l-glutamine can dampen the effects of inflamed environments, we investigated the role of l-glutamine in both differentiating C2C12 myoblasts and existing myotubes in the absence/presence of TNF-alpha (20 ng . ml(-1) ) +/- l-glutamine (20 mM). TNF-alpha reduced the proportion of cells in G1 phase, as well as biochemical (CK activity) and morphological differentiation (myotube number), with corresponding reductions in transcript expression of: Myogenin, Igf-I, and Igfbp5. Furthermore, when administered to mature myotubes, TNF-alpha induced myotube loss and atrophy underpinned by reductions in Myogenin, Igf-I, Igfbp2, and glutamine synthetase and parallel increases in Fox03, Cfos, p53, and Bid gene expression. Investigation of signaling activity suggested that Akt and ERK1/2 were unchanged, JNK increased (non-significantly) whereas P38 MAPK substantially and significantly increased in both myoblasts and myotubes in the presence of TNF alpha. Importantly, 20 mM l-glutamine reduced p38 MAPK activity in TNF-alpha conditions back to control levels, with a corresponding rescue of myoblast differentiation and a reversal of atrophy in myotubes. l-glutamine resulted in upregulation of genes associated with growth and survival including; Myogenin, Igf-Ir, Myhc2 & 7, Tnfsfr1b, Adra1d, and restored atrophic gene expression of Fox03 back to baseline in TNF-alpha conditions. In conclusion, l-glutamine supplementation rescued suppressed muscle cell differentiation and prevented myotube atrophy in an inflamed environment via regulation of p38 MAPK. l glutamine administration could represent an important therapeutic strategy for reducing muscle loss in catabolic diseases and inflamed ageing. J. Cell. Physiol. 9999: 231: 2720-2732, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991745 TI - Partial validation of a French version of the ADHD-rating scale IV on a French population of children with ADHD and epilepsy. Factorial structure, reliability, and responsiveness. AB - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a well-known comorbidity in children with epilepsy. In English-speaking countries, the scores of the original ADHD-rating scale IV are currently used as main outcomes in various clinical trials in children with epilepsy. In French-speaking countries, several French versions are in use though none has been fully validated yet. We sought here for a partial validation of a French version of the ADHD-RS IV regarding construct validity, internal consistency (i.e., scale reliability), item reliability, and responsiveness in a group of French children with ADHD and epilepsy. METHOD: The study involved 167 children aged 6-15years in 10 French neuropediatric units. The factorial structure and item reliability were assessed with a confirmatory factorial analysis for ordered categorical variables. The dimensions' internal consistency was assessed with Guttman's lambda 6 coefficient. The responsiveness was assessed by the change in score under methylphenidate and in comparison with a control group. RESULTS: The results confirmed the original two-dimensional factorial structure (inattention, hyperactivity/impulsivity) and showed a satisfactory reliability of most items, a good dimension internal consistency, and a good responsiveness of the total score and the two subscores. CONCLUSION: The studied French version of the ADHD-RS IV is thus validated regarding construct validity, reliability, and responsiveness. It can now be used in French-speaking countries in clinical trials of treatments involving children with ADHD and epilepsy. The full validation requires further investigations. PMID- 26991746 TI - The interictal dysphoric disorder of epilepsy: Legend or reality? AB - For a long time, the relationships between epilepsy and mood disorders captured the attention of clinicians and neuroscientists. The existence of a peculiar clinical presentation for mood disorders in epilepsy has been a matter of debate since the early reports of Kraepelin and Bleuler. The interictal dysphoric disorder (IDD) represents the modern reinterpretation of such early observations. This paper reviews current research on this topic discussing clinical implications, phenomenological observations, and directions for future research. PMID- 26991747 TI - Ischemic stroke subtype is associated with outcome in thrombolyzed patients. AB - OBJECTIVES: The impact of ischemic stroke subtype on clinical outcome in patients treated with intravenous tissue-type plasminogen activator (IV-tPA) is sparsely examined. We studied the association between stroke subtype and clinical outcome in magnetic resonance imaging (MRI)-evaluated patients treated with IV-tPA. MATERIAL AND METHODS: We conducted a single-center retrospective analysis of MRI selected stroke patients treated with IV-tPA between 2004 and 2010. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish the stroke subtype by 3 months. The outcomes of interest were a 3-month modified Rankin Scale score of 0-1 (favorable outcome), and early neurological improvement defined as complete remission of neurological deficit or improvement of >=4 on the National Institute of Health Stroke Scale at 24 h. The outcomes among stroke subtypes were compared with multivariable logistic regression. RESULTS: Among 557 patients, 202 (36%) had large vessel disease (LVD), 153 (27%) cardioembolic stroke (CE), 109 (20%) small vessel disease, and 93 (17%) were of other or undetermined etiology. Early neurological improvement was present in 313 (56.4%) patients, and 361 (64.8%) patients achieved a favorable outcome. Early neurological improvement and favorable outcome were more likely in CE patients compared with LVD patients (odds ratio (OR), 2.1 (95% confidence interval, 1.4 3.3), and 2.0 (95% confidence interval, 1.2-3.3), respectively). CONCLUSIONS: Cardioembolic stroke patients were more likely to achieve early neurological improvement and favorable outcome compared with LVD stroke following MRI-based IV tPA treatment. This finding may reflect a difference in the effect of IV-tPA among stroke subtypes. PMID- 26991748 TI - From varices to venous ulceration: the story of chronic venous disease described by metalloproteinases. AB - Chronic venous disease (CVD) and its most frightening complication, chronic venous ulceration (CVU), represent an important socioeconomic burden in the western world. Metalloproteinases have been identified in the pathogenesis of several vascular diseases such as venous problems. The aim of this study was to evaluate a broad range of metalloproteinases, such as matrix metalloproteinases (MMPs), ADAMs (a disintegrin and metalloproteinases) and ADAMTSs (a disintegrin and metalloproteinases with thrombospondin motifs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) and a related protein, neutrophil gelatinase-associated lipocalin (NGAL), in patients with CVD in order to correlate their serum levels with each stage of the disease. We performed a multicenter open-label study that comprised the enrolment of 541 patients with CVD of clinical stages C1-C6, (178 males, 363 females; mean age 57.29, median age 53.72, age range 29-81); 29 subjects without CVD were included in this study (9 males and 20 females; mean age 54.44, median age 50, age range 28-84) as the control group. Enzyme-linked immunosorbent assay (ELISA) was performed for measuring serum levels of proteases and related proteins. The study found that the serum elevation of MMP-2, ADAMTS-1 and ADAMTS-7 appeared to be correlated with the initial stages of CVD, whereas the serum elevation of MMP-1, MMP-8, MMP 9, NGAL, ADAM-10, ADAM-17 and ADAMTS-4 was particularly involved in skin change complications. This study showed that each stage of CVD may be described by particular patterns of metalloproteinases, and this may have therapeutic implications in discovering new targets and new drugs for the treatment of CVD. PMID- 26991749 TI - Copper elevated embryonic hemoglobin through reactive oxygen species during zebrafish erythrogenesis. AB - Copper, as an essential trace mineral, can cause diseases such as childhood leukemia at excess levels, but has been applied in anemia therapy for a long time. However, few reports have studied its role during hematopoiesis at the molecular level in an animal model. In this study, by microarray, qRT-PCR, whole mount in situ hybridization and O-dianisidine staining detections, we revealed the increased expression of hemoglobin in copper-exposed embryos. Secondly, we found that copper-exposed embryos exhibited high levels of reactive oxygen species (ROS), and genes in oxygen binding and oxygen transporting were up regulated in the embryos. Finally, we found that ROS scavengers NAC, GSH, and DMTU not only inhibited in vivo ROS levels induced by copper, but also significantly decreased high expression of hemoglobin back to almost normal levels in copper exposed embryos, and also helped with copper elimination from the embryos. Our data first demonstrated that ROS mediated copper induced hemoglobin expression in vertebrates, partly revealing the underlying molecular mechanism of copper therapy for anemia. Moreover, we revealed that copper homeostasis was broken by its induced ROS and ROS helped with copper overloading in the body, which could be applied as a novel therapy target for copper-caused diseases. PMID- 26991750 TI - Local connected fractal dimension analysis in gill of fish experimentally exposed to toxicants. AB - An operator-neutral method was implemented to objectively assess European seabass, Dicentrarchus labrax (Linnaeus, 1758) gill pathology after experimental exposure to cadmium (Cd) and terbuthylazine (TBA) for 24 and 48h. An algorithm derived local connected fractal dimension (LCFD) frequency measure was used in this comparative analysis. Canonical variates (CVA) and linear discriminant analysis (LDA) were used to evaluate the discrimination power of the method among exposure classes (unexposed, Cd exposed, TBA exposed). Misclassification, sensitivity and specificity, both with original and cross-validated cases, were determined. LCFDs frequencies enhanced the differences among classes which were visually selected after their means, respective variances and the differences between Cd and TBA exposed means, with respect to unexposed mean, were analyzed by scatter plots. Selected frequencies were then scanned by means of LDA, stepwise analysis, and Mahalanobis distance to detect the most discriminative frequencies out of ten originally selected. Discrimination resulted in 91.7% of cross-validated cases correctly classified (22 out of 24 total cases), with sensitivity and specificity, respectively, of 95.5% (1 false negative with respect to 21 really positive cases) and 75% (1 false positive with respect to 3 really negative cases). CVA with convex hull polygons ensured prompt, visually intuitive discrimination among exposure classes and graphically supported the false positive case. The combined use of semithin sections, which enhanced the visual evaluation of the overall lamellar structure; of LCFD analysis, which objectively detected local variation in complexity, without the possible bias connected to human personnel; and of CVA/LDA, could be an objective, sensitive and specific approach to study fish gill lamellar pathology. Furthermore this approach enabled discrimination with sufficient confidence between exposure classes or pathological states and avoided misdiagnosis. PMID- 26991751 TI - Endoplasmic reticulum stress and dysregulation of calcium homeostasis mediate Cu induced alteration in hepatic lipid metabolism of javelin goby Synechogobius hasta. AB - The present study was conducted to investigate the effect of Cu exposure on endoplasmic reticulum (ER) stress and Ca(2+) homeostasis, and also explore the underlying mechanism of the ER stress and Ca(2+) homeostasis in the Cu-induced change of hepatic lipid metabolism in javelin goby Synechogobius hasta. To this end, four experiments were conducted. In experiment 1, the full-length cDNA sequences of two ER molecular chaperones [glucose-regulated protein 78 (GRP78) and calreticulin (CRT)] and three ER stress sensors [PKR-like ER kinase (PERK), inositol requiring enzyme (IRE)-1alpha, and activating transcription factor (ATF) 6alpha] cDNAs were firstly characterized from S. hasta. The predicted amino acid sequences for the S. hasta GRP78, CRT, PERK, IRE-1alpha and ATF-6alpha revealed that the proteins contained all of the structural features characteristic in other species. mRNAs of the five genes were expressed in various tissues, but their mRNA levels varied among tissues. In experiment 2, S. hasta were exposed to four waterborne Cu concentrations (control, 19MUg/l, 38MUg/l, and 57MUg/l, respectively) for 60days. Cu exposure evoked ER stress in liver of S. hasta in a time- and concentration-course change. In experiment 3, specific inhibitors, 2 aminoethyldiphenyl borate (2-APB) and dantrolene, were used to explore whether Ca(2+) release from ER was involved in the Cu-induced ER stress change. Dantrolene and 2-APB prevented Cu-induced intracellular Ca(2+) elevation, which demonstrated the release of Ca(2+) from the ER was mediated by both RyR and IP3R. In experiment 4, a chemical chaperone, 4-phenyl butyric acid (4-PBA), was used to demonstrate whether Cu-induced alteration in lipid metabolism was suppressed through the attenuation of ER stress. Cu exposure evoked ER stress and sterol regulator element-binding protein-1c (SREBP-1c) activation in hepatocytes of S. hasta, resulting in dysregulation of hepatic lipid metabolism. 4-PBA attenuated the Cu-induced elevation of mRNA expression of ER stress-related genes. For the first time, our study cloned GRP78, CRT, PERK, IRE-1alpha and ATF-6alpha genes in S. hasta and demonstrated their differential expression among tissues. Moreover, the study demonstrated the molecular mechanism by which ER stress might underlie the change of lipid metabolism induced by Cu in S. hasta. PMID- 26991752 TI - Altered bioenergetics and developmental effects in striped marsh frog (Limnodynastes peronii) tadpoles exposed to UV treated sewage. AB - Effectively treating domestic wastewater so that it can be safely discharged or reused is critical for maintaining the integrity of freshwater resources, and for protecting the health of animals that rely on these systems. Amphibians are currently facing widespread population declines, so there is a particularly urgent need to investigate exposure scenarios that might result in weakened amphibian populations. Domestic sewage has received little attention as a possible factor that could influence the survival, growth and development, or general health of amphibians. However, wastewater reuse for crop irrigation and other purposes is increasing and holding ponds and constructed wetlands exist at many wastewater treatment facilities, introducing conceivable pathways that could result in the exposure of amphibians to treated wastewater. We exposed developing striped marsh frog (Limnodynastes peronii) tadpoles, to control water and 12.5, 25, 50 and 100% UV treated domestic sewage, and quantified effects on growth and development, hepatic energy reserves, and enzymatic pathways associated with detoxification and oxidative stress. Growth and development were accelerated and relative liver size was increased in exposed animals. The exposure resulted in an apparently hormetic increase in hepatic triglycerides and dose-dependent reduction in glycogen stores, as well as increased lipase and NADPH activity, indicating a general disruption to energy metabolism and/or mobilization. Contrary to expectations based on published studies with fish, we found no evidence of lipid peroxidation or induction of the detoxification enzyme Superoxide Dismutase (SOD), however, this may reflect the use of UV treatment as opposed to chlorination for disinfection. Chemical analysis and risk-based prioritization consistently identified fluoxetine, triclosan and diazinon as high risk contaminants in the wastewater, with nonylphenol and mestranol flagged as risks during one early collection. Research is needed to explore the potential for these specific contaminants to elicit the responses identified in the present study, and to perform similar assessments using wastewater from other locations with different treatment options. PMID- 26991753 TI - Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats. AB - BACKGROUND: Although emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal. The objective of this study was to test the hypothesis that physostigmine, a centrally acting cholinesterase inhibitor, induces reanimation from isoflurane anesthesia in adult rats. METHODS: The dose-dependent effects of physostigmine on time to emergence from a standardized isoflurane general anesthetic were tested. It was then determined whether physostigmine restores righting during continuous isoflurane anesthesia. In a separate group of rats with implanted extradural electrodes, physostigmine was administered during continuous inhalation of 1.0% isoflurane, and the electroencephalogram changes were recorded. Finally, 2.0% isoflurane was used to induce burst suppression, and the effects of physostigmine and methylphenidate on burst suppression probability (BSP) were tested. RESULTS: Physostigmine delayed time to emergence from isoflurane anesthesia at doses >=0.2 mg/kg (n = 9). During continuous isoflurane anesthesia (0.9% +/- 0.1%), physostigmine did not restore righting (n = 9). Blocking the peripheral side effects of physostigmine with the coadministration of glycopyrrolate (a muscarinic antagonist that does not cross the blood-brain barrier) produced similar results (n = 9 each). However, during inhalation of 1.0% isoflurane, physostigmine shifted peak electroencephalogram power from delta (<4 Hz) to theta (4-8 Hz) in 6 of 6 rats. During continuous 2.0% isoflurane anesthesia, physostigmine induced large, statistically significant decreases in BSP in 6 of 6 rats, whereas methylphenidate did not. CONCLUSIONS: Unlike methylphenidate, physostigmine does not accelerate time to emergence from isoflurane anesthesia and does not restore righting during continuous isoflurane anesthesia. However, physostigmine consistently decreases BSP during deep isoflurane anesthesia, whereas methylphenidate does not. These findings suggest that activation of cholinergic neurotransmission during isoflurane anesthesia produces arousal states that are distinct from those induced by monoaminergic activation. PMID- 26991755 TI - Anti-leukaemic effects induced by APR-246 are dependent on induction of oxidative stress and the NFE2L2/HMOX1 axis that can be targeted by PI3K and mTOR inhibitors in acute myeloid leukaemia cells. AB - The small molecule APR-246 (PRIMA-1(MET) ) is a novel drug that restores the activity of mutated and unfolded TP53 protein. However, the mechanisms of action and potential off-target effects are not fully understood. Gene expression profiling in TP53 mutant KMB3 acute myeloid leukaemia (AML) cells showed that genes which protected cells from oxidative stress to be the most up-regulated. APR-246 exposure also induced reactive oxygen species (ROS) formation and depleted glutathione in AML cells. The genes most up-regulated by APR-246, confirmed by quantitative real time polymerase chain reaction, were heme oxygenase-1 (HMOX1, also termed HO-1), SLC7A11 and RIT1. Up-regulation of HMOX1, a key regulator of cellular response to ROS, was independent of TP53 mutational status. NFE2L2 (also termed Nrf2), a master regulator of HMOX1 expression, showed transcriptional up-regulation and nuclear translocation by APR-246. Down regulation of NFE2L2 by siRNA in AML cells significantly increased the antitumoural effects of APR-246. The PI3K inhibitor wortmannin and the mTOR inhibitor rapamycin inhibited APR-246-induced nuclear translocation of NFE2L2 and counteracted the protective cellular responses to APR-246, resulting in synergistic cell killing together with APR-246. In conclusion, ROS induction is important for antileukaemic activities of APR-246 and inhibiting the protective response of the Nrf-2/HMOX1 axis using PI3K inhibitors, enhances the antileukaemic effects. PMID- 26991756 TI - Development of a high-resolution melting analysis assay for rapid and high throughput identification of clinically important dermatophyte species. AB - Accurate identification of dermatophyte species is important both for epidemiological studies and for implementing antifungal treatment strategies. Although nucleic acid amplification-based assays have several advantages over conventional mycological methods, a major disadvantage is their high cost. The aim of this study was to develop a rapid and accurate real-time PCR-based high resolution melting (HRM) assay for differentiation of the most common dermatophyte species. The oligonucleotide primers were designed to amplify highly conserved regions of the dermatophyte ribosomal DNA. Analysis of a panel containing potentially interfering fungi demonstrated no cross reactivity with the assay. To evaluate the performance characteristics of the method, a total of 250 clinical isolates were tested in comparison with the long-established PCR RFLP method and the results were reassessed using DNA sequencing, as the reference standard method. The assay is able to type dermatophytes using normalised melting peak, difference plot analysis or electrophoresis on agarose gel methods. The results showed that, in comparison to PCR-RFLP, the developed HRM assay was able to differentiate at least 10 common dermatophytes species with a higher speed, throughput and accuracy. These results indicate that the HRM assay will be a useful sensitive, high throughput and cost-effective method for differentiating the most common dermatophyte species. PMID- 26991757 TI - 1,2-Thiazines: One-Pot Syntheses Utilizing Mono and Diaza Analogs of Sulfones. AB - A one-pot Michael addition/cyclization/condensation reaction sequence for the regioselective synthesis of 1,2-thiazines, starting from propargyl ketones and NH sulfoximines or NH-sulfondiimines, has been developed. Under mild and operationally simple reaction conditions previously unprecedented 1,2-thiazine 1 imide and 1-oxide derivatives are formed in good to excellent yields. The products represent heterocyclic building blocks, readily modifiable by a regioselective C-H bond functionalization, classical cross-coupling reactions, and deprotection. PMID- 26991754 TI - High Glucose Attenuates Anesthetic Cardioprotection in Stem-Cell-Derived Cardiomyocytes: The Role of Reactive Oxygen Species and Mitochondrial Fission. AB - BACKGROUND: Hyperglycemia can blunt the cardioprotective effects of isoflurane in the setting of ischemia-reperfusion injury. Previous studies suggest that reactive oxygen species (ROS) and increased mitochondrial fission play a role in cardiomyocyte death during ischemia-reperfusion injury. To investigate the role of glucose concentration in ROS production and mitochondrial fission during ischemia-reperfusion (with and without anesthetic protection), we used the novel platform of human-induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs). METHODS: Cardiomyocyte differentiation from iPSC was characterized by the expression of CM-specific markers using immunohistochemistry and by measuring contractility. iPSC-CMs were exposed to varying glucose conditions (5, 11, and 25 mM) for 24 hours. Mitochondrial permeability transition pore opening, cell viability, and ROS generation endpoints were used to assess the effects of various treatment conditions. Mitochondrial fission was monitored by the visualization of fragmented mitochondria using confocal microscopy. Expression of activated dynamin-related protein 1, a key protein responsible for mitochondrial fission, was assessed by Western blot. RESULTS: Cardiomyocytes were successfully differentiated from iPSC. Elevated glucose conditions (11 and 25 mM) significantly increased ROS generation, whereas only the 25-mM high glucose condition induced mitochondrial fission and increased the expression of activated dynamin-related protein 1 in iPSC-CMs. Isoflurane delayed mitochondrial permeability transition pore opening and protected iPSC-CMs from oxidative stress in 5- and 11-mM glucose conditions to a similar level as previously observed in various isolated animal cardiomyocytes. Scavenging ROS with Trolox or inhibiting mitochondrial fission with mdivi-1 restored the anesthetic cardioprotective effects in iPSC-CMs in 25-mM glucose conditions. CONCLUSIONS: Human iPSC-CM is a useful, relevant model for studying isoflurane cardioprotection and can be manipulated to recapitulate complex clinical perturbations. We demonstrate that the cardioprotective effects of isoflurane in elevated glucose conditions can be restored by scavenging ROS or inhibiting mitochondrial fission. These findings may contribute to further understanding and guidance for restoring pharmacological cardioprotection in hyperglycemic patients. PMID- 26991758 TI - Usefulness of Housekeeping Genes for the Diagnosis of Helicobacter pylori Infection, Strain Discrimination and Detection of Multiple Infection. AB - BACKGROUND: Helicobacter pylori infects human stomachs of over half the world's population, evades the immune response and establishes a chronic infection. Although most people remains asymptomatic, duodenal and gastric ulcers, MALT lymphoma and progression to gastric cancer could be developed. Several virulence factors such as flagella, lipopolysaccharide, adhesins and especially the vacuolating cytotoxin VacA and the oncoprotein CagA have been described for H. pylori. Despite the extensive published data on H. pylori, more research is needed to determine new virulence markers, the exact mode of transmission or the role of multiple infection. MATERIALS AND METHODS: Amplification and sequencing of six housekeeping genes (amiA, cgt, cpn60, cpn70, dnaJ, and luxS) related to H. pylori pathogenesis have been performed in order to evaluate their usefulness for the specific detection of H. pylori, the genetic discrimination at strain level and the detection of multiple infection. A total of 52 H. pylori clones, isolated from 14 gastric biopsies from 11 patients, were analyzed for this purpose. RESULTS: All genes were specifically amplified for H. pylori and all clones isolated from different patients were discriminated, with gene distances ranged from 0.9 to 7.8%. Although most clones isolated from the same patient showed identical gene sequences, an event of multiple infection was detected in all the genes and microevolution events were showed for amiA and cpn60 genes. CONCLUSIONS: These results suggested that housekeeping genes could be useful for H. pylori detection and to elucidate the mode of transmission and the relevance of the multiple infection. PMID- 26991759 TI - The Conformational Variability of FimH: Which Conformation Represents the Therapeutic Target? AB - FimH is a bacterial lectin found at the tips of type 1 pili of uropathogenic Escherichia coli (UPEC). It mediates shear-enhanced adhesion to mannosylated surfaces. Binding of UPEC to urothelial cells initiates the infection cycle leading to urinary tract infections (UTIs). Antiadhesive glycomimetics based on alpha-d-mannopyranose offer an attractive alternative to the conventional antibiotic treatment because they do not induce a selection pressure and are therefore expected to have a reduced resistance potential. Genetic variation of the fimH gene in clinically isolated UPEC has been associated with distinct mannose binding phenotypes. For this reason, we investigated the mannose binding characteristics of four FimH variants with mannose-based ligands under static and hydrodynamic conditions. The selected FimH variants showed individually different binding behavior under both sets of conditions as a result of the conformational variability of FimH. Clinically relevant FimH variants typically exist in a dynamic conformational equilibrium. Additionally, we evaluated inhibitory potencies of four FimH antagonists representing different structural classes. Inhibitory potencies of three of the tested antagonists were dependent on the binding phenotype and hence on the conformational equilibrium of the FimH variant. However, the squarate derivative was the notable exception and inhibited FimH variants irrespective of their binding phenotype. Information on antagonist affinities towards various FimH variants has remained largely unconsidered despite being essential for successful antiadhesion therapy. PMID- 26991760 TI - A novel EDARADD 5'-splice site mutation resulting in activation of two alternate cryptic 5'-splice sites causes autosomal recessive Hypohidrotic Ectodermal Dysplasia. PMID- 26991761 TI - Preparation of l-phenylalanine-imprinted solid-phase extraction sorbent by Pickering emulsion polymerization and the selective enrichment of l-phenylalanine from human urine. AB - A novel l-phenylalanine molecularly imprinted solid-phase extraction sorbent was synthesized by the combination of Pickering emulsion polymerization and ion-pair dummy template imprinting. Compared to other polymerization methods, the molecularly imprinted polymers thus prepared exhibit a high specific surface, large pore diameter, and appropriate particle size. The key parameters for solid phase extraction were optimized, and the result indicated that the molecularly imprinted polymer thus prepared exhibits a good recovery of 98.9% for l phenylalanine. Under the optimized conditions of the procedure, an analytical method for l-phenylalanine was well established. By comparing the performance of the molecularly imprinted polymer and a commercial reverse-phase silica gel, the obtained molecularly imprinted polymer as an solid-phase extraction sorbent is more suitable, exhibiting high precision (relative standard deviation 3.2%, n = 4) and a low limit of detection (60.0 +/- 1.9 nmol.L(-1) ) for the isolation of l phenylalanine. Based on these results, the combination of the Pickering emulsion polymerization and ion-pair dummy template imprinting is effective for preparing selective solid-phase extraction sorbents for the separation of amino acids and organic acids from complex biological samples. PMID- 26991762 TI - Increased airway inflammation in patients with psoriasis. PMID- 26991763 TI - A Three-Photon Active Organic Fluorophore for Deep Tissue Ratiometric Imaging of Intracellular Divalent Zinc. AB - Deep tissue bioimaging with three-photon (3P) excitation using near-infrared (NIR) light in the second IR window (1.0-1.4 MUm) could provide high resolution images with an improved signal-to-noise ratio. Herein, we report a photostable and nontoxic 3P excitable donor-pi-acceptor system (GMP) having 3P cross-section (sigma3 ) of 1.78*10(-80) cm(6) s(2) photon(-2) and action cross-section (sigma3 eta3 ) of 2.31*10(-81) cm(6) s(2) photon(-2) , which provides ratiometric fluorescence response with divalent zinc ions in aqueous conditions. The probe signals the Zn(2+) binding at 530 and 600 nm, respectively, upon 1150 nm excitation with enhanced sigma3 of 1.85*10(-80) cm(6) s(2) photon(-2) and sigma3 eta3 of 3.33*10(-81) cm(6) s(2) photon(-2) . The application of this probe is demonstrated for ratiometric 3P imaging of Zn(2+) in vitro using HuH-7 cell lines. Furthermore, the Zn(2+) concentration in rat hippocampal slices was imaged at 1150 nm excitation after incubation with GMP, illustrating its potential as a 3P ratiometric probe for deep tissue Zn(2+) ion imaging. PMID- 26991764 TI - The Effects of Profile Pictures and Friends' Comments on Social Network Site Users' Body Image and Adherence to the Norm. AB - This study sought to explore the effects of exposure to Facebook body ideal profile pictures and norm conforming comments on users' body image. In addition, the social identity and self-categorization theoretical frameworks were used to explore users' endorsement of a body ideal norm. A mock Facebook page was used to conduct a pretest posttest 2 * 2 between-group web-based experiment that featured body ideal profile pictures (body ideal vs. no body) and body ideal comments (conforming vs. nonconforming). Five hundred and one participants completed the experiment and passed all manipulation checks. Participants viewed pictures and comments on the status page and were able to leave their own comment before exiting. Results demonstrated no significant main effects. However, predispositional body satisfaction significantly moderated the relationship between body ideal pictures and body satisfaction. Most comments supported the body ideal norm. However, in support of self-categorization theory, participants exposed to nonconforming comments made nonconforming comments themselves significantly more than those exposed to conforming comments. The findings demonstrated the importance of continued body image research in social network sites, as well as the potential for self-categorization theory to guide such research. PMID- 26991765 TI - Contextual influence of Taiwanese adolescents' sexual attitudes and behavioral intent. AB - This study examined parental, peer, and media influences on Taiwanese adolescents' attitudes toward premarital sex and intent to engage in sexual behavior. Participants included a convenience sample of 186 adolescents aged 13 15 recruited from two middle schools in Taiwan. Parental influence was indicated by perceived parental disapproval toward premarital sex and perceived peer sexual behavior was used to measure peer influence. Media influence was measured by the adolescents' perception of whether the media promotes premarital sex. We conducted structural equation modeling to test a hypothesized model. The findings suggested that the perceived sexual behavior of peers had the strongest effect on Taiwanese adolescents' sexual attitudes and behavioral intent, while parental disapproval and media influence also significantly contributed to adolescents' sexual attitudes and intent to engage in sex. School nurses are in an ideal position to coordinate essential resources and implement evidence-based sexually transmitted infection and HIV/AIDS prevention interventions that address issues associated with the influence of parents, peers, and media. PMID- 26991766 TI - Clinical value to quantitate hematogones in Chinese childhood acute lymphoblastic leukemia by flow cytometry analysis. AB - INTRODUCTION: Past studies have shown hematogones (HGs) become prominent in recovery phase after chemotherapy or hematopoietic stem cell transplantation, but still need further researches including different age, centers, and races to prove. So we provide relevant information regarding the clinical impact of this methodology in monitoring the response to treatment. METHODS: HGs in 279 consecutive ALL patients at a time frame of postconsolidation treatment were recorded by flow cytometric minimal residual disease techniques according to the European BIOMED-1 standard. Patients divided by risk stratification, clinical phases and cytogenesis test were judged. RESULTS: Total HGs correlated inversely with age but not with >2 years, significant difference existed between <=2 years and >2 years. HGs in low-risk patients were much higher than that in intermediate and high-risk patients (P < 0.01), significant difference (P < 0.05) was also found for HGs quantitation between patients experiencing hematological complete remission and relapse. Total HGs and Pro-B+immature B HGs in patients with TEL AML1 were much higher than those with BCR-ABL and MLL-AF4 (P < 0.01). HGs > 1% of TNCs had significantly prolonged event-free survival (EFS) (P < 0.01); Multivariate analysis indicated HGs was independently associated with the longer EFS. CONCLUSION: The strong independently prognostic impact indicated that the better HGs regeneration is a marker of better response to therapy. PMID- 26991767 TI - Lowest Acceptable Bladder Capacity for Interpretation of Uroflowmetry Tests in Children. AB - OBJECTIVE: To determine the age-specific lowest acceptable value of bladder capacity (LABC) for interpretation of uroflowmetry tests in children. METHODS: From September 2008 through July 2012, healthy children aged 4-9 years were enrolled. All children were asked to have two sets of uroflowmetry and post-void residual (PVR) tests. We selected the tests with lower bladder capacity (voided volume+ PVR) of each child to analyze the LABC. Only bell shaped curves were regarded as normal. PVR >20 mL and Qmax <15 mL/s in children aged 4-6 years, and PVR >10 mL, Qmax <15.0 mL/s in children aged 7-9 years were defined as abnormal, respectively. Receiver operative characteristic curves were used to determine the age-specific cut-off value of LABC. The upper boundary of optimal bladder capacity (OBC) for interpretation of uroflowmetry was defined at 115% expected bladder capacity, and LABC as lower boundary. Linear regression was used to establish the relationship between age and LABC. RESULTS: Totally, 930 children were eligible for analysis of LABC. Through ROC curve analysis and regression analysis, the best fitted age specific LABC defined though differentiating low Qmax is 52.08 mL + age in years * 4.78 mL. For simplicity, the proposed LABC is age in years * 5 + 50. Good reproducibility of normal flow pattern, Qmax and PVR in each child were observed in the uroflowmetry tests within OBC. CONCLUSION: Through the large scale study for uroflowmetry tests in children, we proposed the age-specific lowest acceptable bladder capacity for interpretation of uroflowmetry tests as age in years * 5 + 50 mL. PMID- 26991768 TI - Transcriptome dynamics of Arabidopsis during sequential biotic and abiotic stresses. AB - In nature, plants have to cope with a wide range of stress conditions that often occur simultaneously or in sequence. To investigate how plants cope with multi stress conditions, we analyzed the dynamics of whole-transcriptome profiles of Arabidopsis thaliana exposed to six sequential double stresses inflicted by combinations of: (i) infection by the necrotrophic fungus Botrytis cinerea, (ii) herbivory by chewing larvae of Pieris rapae, and (iii) drought stress. Each of these stresses induced specific expression profiles over time, in which one-third of all differentially expressed genes was shared by at least two single stresses. Of these, 394 genes were differentially expressed during all three stress conditions, albeit often in opposite directions. When two stresses were applied in sequence, plants displayed transcriptome profiles that were very similar to the second stress, irrespective of the nature of the first stress. Nevertheless, significant first-stress signatures could be identified in the sequential stress profiles. Bioinformatic analysis of the dynamics of co-expressed gene clusters highlighted specific clusters and biological processes of which the timing of activation or repression was altered by a prior stress. The first-stress signatures in second stress transcriptional profiles were remarkably often related to responses to phytohormones, strengthening the notion that hormones are global modulators of interactions between different types of stress. Because prior stresses can affect the level of tolerance against a subsequent stress (e.g. prior herbivory strongly affected resistance to B. cinerea), the first stress signatures can provide important leads for the identification of molecular players that are decisive in the interactions between stress response pathways. PMID- 26991769 TI - Associations of serum n-3 and n-6 PUFA and hair mercury with the risk of incident stroke in men: the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD). AB - PUFA have been associated with lower risk of CVD, but less is known about their association with stroke risk. Fish, a major source of n-3 PUFA, may also contain methylmercury, which has been associated with higher risk of CVD and attenuation of the benefits of long-chain n-3 PUFA. We investigated the associations of serum n-3 and n-6 PUFA and hair Hg with risk of stroke in men. A total of 1828 men from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 years and free of CVD at baseline in 1984-1989 were studied. Cox regression models were used for the analyses. During the mean follow-up of 21.2 years, 202 stroke cases occurred, of which 153 were ischaemic strokes. After adjustment for age and examination year, the only statistically significant association among the n-3 and n-6 PUFA was observed between the n-3 PUFA alpha linolenic acid and risk of haemorrhagic stroke (hazard ratio in the highest v. the lowest quartile 0.33; 95 % CI 0.13, 0.86; P trend=0.03). However, further adjustments attenuated the association to statistically non-significant. Hair Hg was not associated with stroke risk, but among those with hair Hg above the median level, higher serum long-chain n-3 PUFA concentrations were associated with a higher risk of ischaemic stroke. In our cohort of men, serum n-3 or n-6 PUFA or hair Hg were not associated with stroke risk; however, the interaction between Hg and long-chain n-3 PUFA with regard to ischaemic stroke risk warrants further investigation. PMID- 26991770 TI - A new genus and species of demodecid mites from the tongue of a house mouse Mus musculus: description of adult and immature stages with data on parasitism. AB - The study of the parasitofauna of the house mouse Mus musculus (Rodentia: Muridae) Linnaeus is particularly important owing to its multiple relationships with humans - as a cosmopolitan, synanthropic rodent, bred for pets, food for other animals or laboratory animal. This article proposes and describes a new genus and species of the parasitic mite based on adult and immature stages from the house mouse. Glossicodex musculi gen. n., sp. n. is a medium-sized demodecid mite (adult stages on average 199 um in length) found in mouse tissue of the tongue. It is characterized by two large, hooked claws on each tarsus of the legs; the legs are relatively massive, consisting of large, non-overlapping segments. The palps consist of three slender, clearly separated, relatively narrow segments, wherein their coxal segments are also quite narrow and spaced. Also, segments of the palps of larva and nymphs are clearly isolated, and on the terminal segment, trident claws that resemble legs' claws can be found. On the ventral side, in immature stages, triangular scuta, topped with sclerotized spur, can be also observed. Glossicodex musculi was noted in 10.8% of mice with a mean infection intensity of 2.2 parasites per host. PMID- 26991771 TI - Why Do Nucleosomes Unwrap Asymmetrically? AB - Nucleosomes, DNA spools with a protein core, engage about three-quarters of eukaryotic DNA and play a critical role in chromosomal processes, ranging from gene regulation, recombination, and replication to chromosome condensation. For more than a decade, micromanipulation experiments where nucleosomes are put under tension, as well as the theoretical interpretations of these experiments, have deepened our understanding of the stability and dynamics of nucleosomes. Here we give a theoretical explanation for a surprising new experimental finding: nucleosomes wrapped onto the 601 positioning sequence (the sequence used in most laboratories) respond highly asymmetrically to external forces by always unwrapping from the same end. Using a computational nucleosome model, we show that this asymmetry can be explained by differences in the DNA mechanics of two very short stretches on the wrapped DNA portion. Our finding suggests that the physical properties of nucleosomes, here the response to forces, can be tuned locally by the choice of the underlying base-pair sequence. This leads to a new view of nucleosomes: a physically highly varied set of DNA-protein complexes whose properties can be tuned on evolutionary time scales to their specific function in the genomic context. PMID- 26991772 TI - Vascular Effects of Eplerenone in Coronary Artery Disease With Preserved Ejection Fraction: A Double-Blind, Randomized, Placebo-Controlled Trial. AB - BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Their role in patients without heart failure, particularly in patients with coronary artery disease (CAD) and preserved EF, is still a matter of debate. HYPOTHESIS: The MRA eplerenone on top of standard medical therapy improves endothelial dysfunction and other markers of vascular health in CAD patients with preserved EF. METHODS: In this double-blind, randomized, placebo-controlled study, 42 patients (mean age: 63.5 +/- 9.1 years; 37 males) were randomized to 4-week treatment with eplerenone 25 mg daily or placebo. The primary endpoint was difference in endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery. Secondary endpoints included 24-hour blood pressure (BP), endothelial progenitor cells, and platelet adhesion. RESULTS: No difference in the primary endpoint FMD was noted after 4 weeks of treatment with eplerenone compared with placebo (FMD: 4.7% +/- 2.0% and 4.9% +/- 2.1%, respectively; P = 0.77). There were no significant differences between eplerenone and placebo in 24 hour BP (mean systolic BP: 126.9 +/- 17.3 and 123.3 +/- 9.7 mm Hg, P = 0.41; diastolic BP: 73.3 +/- 12.9 and 72.0 +/- 7.5 mm Hg, respectively, P = 0.69), number of endothelial progenitor cells, and platelet adhesion. CONCLUSIONS: Adding low-dose eplerenone to standard medical therapy did not improve important markers of vascular health in patients with CAD and preserved EF. Our results may help understand conflicting evidence from larger clinical trials on MRAs in patients with preserved EF. PMID- 26991776 TI - Differential Left Hippocampal Activation during Retrieval with Different Types of Reminders: An fMRI Study of the Reconsolidation Process. AB - Consolidated memories return to a labile state after the presentation of cues (reminders) associated with acquisition, followed by a period of stabilization (reconsolidation). However not all cues are equally effective in initiating the process, unpredictable cues triggered it, predictable cues do not. We hypothesize that the different effects observed by the different reminder types on memory labilization-reconsolidation depend on a differential neural involvement during reminder presentation. To test it, we developed a declarative task and compared the efficacy of three reminder types in triggering the process in humans (Experiment 1). Finally, we compared the brain activation patterns between the different conditions using functional magnetic resonance imaging (fMRI) (Experiment 2). We confirmed that the unpredictable reminder is the most effective in initiating the labilization-reconsolidation process. Furthermore, only under this condition there was differential left hippocampal activation during its presentation. We suggest that the left hippocampus is detecting the incongruence between actual and past events and allows the memory to be updated. PMID- 26991777 TI - Limitations, depressive symptoms, and quality of life among a population-based sample of young adults with congenital heart defects. AB - BACKGROUND: Little population-based data exist on limitations and health-related quality of life (HRQoL) in adults with congenital heart defects (CHD). METHODS: We used 2004 to 2012 Medical Expenditure Panel Survey data to identify a population-based sample of young adults ages 18 to 40 years reporting health symptoms or healthcare encounters in the previous year. Comparing adults reporting CHD to others, we examined the prevalence of cognitive, physical, and activity limitations, depressive symptoms, and physical and mental HRQoL. We used chi square tests to examine differences in demographic characteristics, logistic regression to generate adjusted prevalence ratios (aPR), and linear regression to examine HRQoL. Multivariable associations were adjusted for sex, age, race/ethnicity, and smoking status. All analyses were conducted in SUDAAN using weights to account for clustering within sampling units and nonresponse. RESULTS: Fifty-nine adults reported CHD (weighted prevalence = 0.1%; representing 700,000 U.S. adults from 2004 to 2012 or, on average, 80,000 per year) and 54,011 did not. No demographic characteristics differed significantly by CHD status except health insurance; 31.5% of adults with CHD, compared with 11.0% without, reported public insurance (p = 0.01). Compared with their counterparts, adults reporting CHD had a higher prevalence of cognitive (aPR = 2.7, 95% confidence interval (CI): 1.0, 7.2), physical (aPR = 4.0, 95% CI: 1.9, 8.2), and activity limitations (aPR = 4.8, 95% CI: 2.6, 9.1), and poorer physical HRQoL (p = 0.004). No differences were observed in depressive symptoms and mental HRQoL by CHD status. CONCLUSION: Physical health and cognitive abilities of adults with CHD were compromised compared with adults without CHD. Birth Defects Research (Part A) 106:580-586, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991778 TI - Performance of Clinical Risk Model for Prediction of Long-Term Survival Following Coronary Artery Bypass Grafting. PMID- 26991779 TI - Trajectories of marijuana use from adolescence to adulthood as predictors of unemployment status in the early forties. AB - OBJECTIVES: To study the degree to which individuals in different trajectories of marijuana use are similar or different in terms of unemployment status at mean age 43. METHODS: We gathered longitudinal data on a prospective cohort taken from a community sample (N = 548). Forty-nine percent of the original participants were females. Over 90% of the participants were white. The participants were followed from adolescence to early midlife. The mean ages of participants at the follow-up interviews were 14.1, 16.3, 22.3, 27.0, 31.9, 36.6, and 43.0, respectively. We used the growth mixture modeling (GMM) approach to identify the trajectories of marijuana use over a 29-year period. RESULTS: Five trajectories of marijuana use were identified: chronic users/decreasers (8.3%), quitters (18.6%), increasing users (7.3%), chronic occasional users (25.6%), and nonusers/experimenters (40.2%). Compared with nonusers/experimenters, chronic users/decreasers had a significantly higher likelihood of unemployment at mean age 43 (adjusted odds ratio = 3.51, 95% confidence interval = 1.13-10.91), even after controlling for the covariates. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The results of the associations between the distinct trajectories of marijuana use and unemployment in early midlife indicate that it is important to develop intervention programs targeting chronic marijuana use as well as unemployment in individuals at this stage of development. Results from this study should encourage clinicians, teachers, and parents to assess and treat chronic marijuana use in adolescents. PMID- 26991780 TI - A Predictive Model for Selecting Patients with HCV Genotype 3 Chronic Infection with a High Probability of Sustained Virological Response to Peginterferon Alfa 2a/Ribavirin. AB - BACKGROUND: Access to direct-acting antiviral agents (DAAs) is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV) therapy wherever DAAs are unavailable. HCV genotype (GT) 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy. METHODS: Relationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies. RESULTS: The score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years) (<=40: 2 points; >40 but <=55: 1); bodyweight (kg) (<70: 2; >=70 but <90: 1); no cirrhosis/transition to cirrhosis (2); ALT <=2.5 x ULN (1); platelets (109/L) (>200: 2; >=100 but <200: 1); HCV RNA (<400,000 IU/mL: 1). The points are summed to arrive at a score ranging from 0-10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0-4, 5, 6, 7, 8, and 9-10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6-10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622). CONCLUSIONS: A simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy. PMID- 26991781 TI - Low-molecular-weight carbohydrate Pentaisomaltose may replace dimethyl sulfoxide as a safer cryoprotectant for cryopreservation of peripheral blood stem cells. AB - BACKGROUND: Cryopreserved hematopoietic stem cell products are widely used for certain hematologic malignancies. Dimethyl sulfoxide (DMSO) is the most widely used cryoprotective agent (CPA) today, but due to indications of cellular toxicity, changes of the cellular epigenetic state, and patient-related side effects, there is an increasing demand for DMSO-free alternatives. We therefore investigated whether Pentaisomaltose (PIM), a low-molecular-weight carbohydrate (1 kDa), can be used for cryopreservation of peripheral blood stem cells, more specifically hematopoietic progenitor cell apheresis (HPC(A)) product. STUDY DESIGN AND METHODS: We cryopreserved patient or donor HPC(A) products using 10% DMSO or 16% PIM and quantified the recovery of CD34+ cells and CD34+ subpopulations by multicolor flow cytometry. In addition, we compared the frequency of HPCs after DMSO and PIM cryopreservation using the colony-forming cells (CFCs) assay. RESULTS: The mean CD34+ cell recovery was 56.3 +/- 23.7% (11.4%-97.3%) and 58.2 +/- 10.0% (45.7%-76.9%) for 10% DMSO and 16% PIM, respectively. The distribution of CD34+ cell subpopulations was similar when comparing DMSO or PIM as CPA. CFC assay showed mean colony numbers of 70.7 +/- 25.4 (range, 37.8-115.5) and 67.7 +/- 15.7 (range, 48-86) for 10% DMSO and 16% PIM, respectively. CONCLUSION: Our findings demonstrate that PIM cryopreservation of HPC(A) products provides recovery of CD34+ cells, CD34+ subpopulations, and CFCs similar to that of DMSO cryopreservation and therefore may have the potential to be used for cryopreservation of peripheral blood stem cells. PMID- 26991782 TI - A Comparison between CHEK2*1100delC/I157T Mutation Carrier and Noncarrier Breast Cancer Patients: A Clinicopathological Analysis. AB - OBJECTIVE: The suppressor gene CHEK2 encodes a cell cycle checkpoint kinase, involved in cell cycle regulation, apoptosis and response to DNA damage. The aim of this study was to analyze the differences between CHEK2 mutation carriers (CHEK2*1100delC/I157T) and noncarriers with respect to clinicopathological factors. METHODS: We reviewed the medical records of 100 early breast cancer patients (46 mutation carriers and 54 noncarriers) who were treated with chemotherapy, hormonotherapy or trastuzumab. RESULTS: CHEK2 mutation carriers were older (>65 years) than noncarriers (17 vs. 7%; p = 0.215). Twenty-five (54%) of them had a history of cancer in the family. Gastric cancer in the family history was detected in 11% of mutation carriers and in 2% of noncarriers (p = 0.092). There was a trend for more frequent lymph node metastases in patients without the mutation in comparison to mutation carriers (46 vs. 28%; p = 0.098). Luminal B type breast cancer was detected more often in carriers (39 vs. 20%; p = 0.048). Breast-conserving treatment was also conducted more often in mutation carriers (57 vs. 31%; p = 0.015). Histologic grades G1/G2 were detected more frequently in mutation carriers (82 vs. 70%; p = 0.212). CONCLUSION: Mutation carriers were characterized by older age, a history of gastric cancer in the family, locally advanced disease, lower histologic grade and luminal B type breast cancer. PMID- 26991783 TI - Family and College Environmental Exposures Mediate the Relationship between Parental Education and Depression among College Students. AB - BACKGROUND: Depression is a major health concern for college students due to its substantial morbidity and mortality. Although low parental education has been identified as a factor in depression in college students, the mechanisms through which parental educational achievement affects students' depression are not well understood. We tested whether adverse family and college environments mediate the relationship between parental educational level and depression among Chinese college students. METHODS: A total of 5180 respondents were selected using a cross-sectional survey. We examined the association of parental education, adverse family and college environments with depression in college students using the Adolescent Self-Rating Life Events Checklist, Beck Depression Inventory and socio-demographic questionnaires. RESULTS: Lower parental educational level is significantly correlated with depression in college students in our sample. Additionally, low family economic status, paternal or maternal unemployment, long periods spent apart from family, family conflicts, having been scolded and beaten by parents, poor or dissatisfying test performance, conflict with friends, heavy course load and failure in selection processes are also associated with parental education. Low family economic status, paternal or maternal unemployment, long periods spent apart from family, family conflicts, poor or dissatisfying test performance, conflict with friends and heavy course load mediated the relationship between parental education and depression in college students. CONCLUSIONS: Adverse family and college environments could explain the influence of parental educational level on depression in college students. PMID- 26991785 TI - Ligand-Promoted Rh(III)-Catalyzed Coupling of Aryl C-H Bonds with Arylboron Reagents. AB - Rhodium(III)-catalyzed C-H arylation of arenes with phenylboronic acid pinacol esters has been achieved using a readily removable N-pentafluorophenylbenzamide directing group for the first time. The use of a bidentate phosphine ligand (Binap) significantly increased the yield of the cross-coupling of C-H bonds with organoboron reagents. PMID- 26991786 TI - Land Surface Model and Particle Swarm Optimization Algorithm Based on the Model Optimization Method for Improving Soil Moisture Simulation in a Semi-Arid Region. AB - Improving the capability of land-surface process models to simulate soil moisture assists in better understanding the atmosphere-land interaction. In semi-arid regions, due to limited near-surface observational data and large errors in large scale parameters obtained by the remote sensing method, there exist uncertainties in land surface parameters, which can cause large offsets between the simulated results of land-surface process models and the observational data for the soil moisture. In this study, observational data from the Semi-Arid Climate Observatory and Laboratory (SACOL) station in the semi-arid loess plateau of China were divided into three datasets: summer, autumn, and summer-autumn. By combing the particle swarm optimization (PSO) algorithm and the land-surface process model SHAW (Simultaneous Heat and Water), the soil and vegetation parameters that are related to the soil moisture but difficult to obtain by observations are optimized using three datasets. On this basis, the SHAW model was run with the optimized parameters to simulate the characteristics of the land surface process in the semi-arid loess plateau. Simultaneously, the default SHAW model was run with the same atmospheric forcing as a comparison test. Simulation results revealed the following: parameters optimized by the particle swarm optimization algorithm in all simulation tests improved simulations of the soil moisture and latent heat flux; differences between simulated results and observational data are clearly reduced, but simulation tests involving the adoption of optimized parameters cannot simultaneously improve the simulation results for the net radiation, sensible heat flux, and soil temperature. Optimized soil and vegetation parameters based on different datasets have the same order of magnitude but are not identical; soil parameters only vary to a small degree, but the variation range of vegetation parameters is large. PMID- 26991784 TI - Oral secretions from Mythimna separata insects specifically induce defence responses in maize as revealed by high-dimensional biological data. AB - Attack from insect herbivores poses a major threat to plant survival, and accordingly, plants have evolved sophisticated defence systems. Maize is cultivated as a staple crop worldwide, and insect feeding causes large production losses. Despite its importance in agriculture, little is known about how maize reacts to insect herbivory. Taking advantage of advances in sequencing and mass spectrometry technology, we studied the response of maize to mechanical wounding and simulated Mythimna separata (a specialist insect) herbivory by applying its oral secretions (OS) to wounds. In comparison to the responses induced by mechanical wounding, OS elicited larger and longer-lasting changes in the maize transcriptome, proteome, metabolome and phytohormones. Specifically, many genes, proteins and metabolites were uniquely induced or repressed by OS. Nearly 290 transcription factor genes from 39 families were involved in OS-induced responses, and among these, more transcription factor genes were specifically regulated by OS than by wounding. This study provides a large-scale omics dataset for understanding maize response to chewing insects and highlights the essential role of OS in plant-insect interactions. PMID- 26991788 TI - Paid Maternity Leave and Breastfeeding Outcomes. AB - BACKGROUND: Despite the benefits of breastfeeding, rates in the United States are low. Shorter maternity leave is associated with lower initiation and shorter durations of breastfeeding; however, little is known about how paid maternity leave may influence breastfeeding rates. METHODS: We used data from the 2006-2010 U.S. National Survey of Family Growth on the most recent birth to employed women who delivered a child within the previous 5 years. Separate multivariable logistic regression models were used to describe the associations between paid leave duration (0, 1-5, 6-11, >= 12 weeks, maternity leave not taken) and three outcomes: 1) breastfeeding initiation, 2) 6-month duration, and 3) 6-month duration among initiators. RESULTS: Twenty-eight percent of prenatally employed women received no paid leave. Women who received 12 or more weeks of paid leave were more likely to initiate breastfeeding compared to women with no paid leave (87.3% vs 66.7%, adjusted odds ratio [aOR] 2.83 [95% confidence interval {CI} 1.23-6.48]). Similarly, women with 12 or more weeks of paid leave were more likely to breastfeed at 6 months, compared to women with no paid leave (24.9% vs 50.1%, aOR 2.26 [95% CI 1.20-4.26]). Among women who initiated breastfeeding, having received 12 or more weeks' paid leave increased the odds of breastfeeding for 6 or more months; however, the association was not statistically significant in the adjusted model (aOR 1.81 [95% CI 0.93-3.52]). CONCLUSIONS: Employed women who received 12 or more weeks of paid maternity leave were more likely to initiate breastfeeding and be breastfeeding their child at 6 months than those without paid leave. PMID- 26991787 TI - Epithelial and organ-related marker expression in pituitary adenomas. AB - The histologic expression of epithelial and organ-related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ-related differentiation markers (gross cystic disease fluid protein-15 (GCDFP-15), thyroid transcription factor-1 (TTF-1), Napsin A, paired box 8 (PAX-8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub-types. Non-parametric statistical procedures were used to examine associations between marker expression and tumor sub-type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic-type morphology. The specificity of organ-related differentiation markers was 100% (monoclonal Napsin A, GCDFP-15 and TTF-1), 97% (HepPar1 and PAX-8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co-expression of these organ-related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic-type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo-stellate cell-type differentiation, as these also have dendritic cell-type morphology and express CK7 in non-neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic confirmation of that sub-type. The final conclusion is in regard to those features that separate adenomas from sellar region metastases: adenomas do not demonstrate significant expression of TTF-1, monoclonal Napsin A, PAX-8, HepPar1 or GCDFP-15, nor do they exhibit diffuse expression of CK7 and CK20. PMID- 26991789 TI - Preadolescents Solve Natural Syllogisms Proficiently. AB - "Natural syllogisms" are arguments formally identifiable with categorical syllogisms that have an implicit universal affirmative premise retrieved from semantic memory rather than explicitly stated. Previous studies with adult participants (Politzer, 2011) have shown that the rate of success is remarkably high. Because their resolution requires only the use of a simple strategy (known as ecthesis in classic logic) and an operational use of the concept of inclusion (the recognition that an element that belongs to a subset must belong to the set but not vice versa), it was hypothesized that these syllogisms would be within the grasp of non-adult participants, provided they have acquired the notion of deductive validity. Here, 11-year-old children were presented with natural syllogisms embedded in short dialogs. The first experiment showed that their performance was equivalent to adults' highest level of performance in standard experiments on syllogisms. The second experiment, while confirming children's proficiency in solving natural syllogisms, showed that they outperformed children who solved non-natural matched syllogisms in the same experimental setting. The results are also in agreement with the argumentation theory of reasoning. PMID- 26991790 TI - Nitrogen Fertilization Effects on Productivity and Nitrogen Loss in Three Grass Based Perennial Bioenergy Cropping Systems. AB - Nitrogen (N) fertilization can greatly improve plant productivity but needs to be carefully managed to avoid harmful environmental impacts. Nutrient management guidelines aimed at reducing harmful forms of N loss such as nitrous oxide (N2O) emissions and nitrate (NO3(-)) leaching have been tailored for many cropping systems. The developing bioenergy industry is likely to make use of novel cropping systems, such as polycultures of perennial species, for which we have limited nutrient management experience. We studied how a switchgrass (Panicum virgatum) monoculture, a 5-species native grass mixture and an 18-species restored prairie responded to annual fertilizer applications of 56 kg N ha(-1) in a field-scale agronomic trial in south-central Wisconsin over a 2-year period. We observed greater fertilizer-induced N2O emissions and sub-rooting zone NO3(-) concentrations in the switchgrass monoculture than in either polyculture. Fertilization increased aboveground net primary productivity in the polycultures, but not in the switchgrass monoculture. Switchgrass was generally more productive, while the two polycultures did not differ from each other in productivity or N loss. Our results highlight differences between polycultures and a switchgrass monoculture in responding to N fertilization. PMID- 26991791 TI - Imidazolium-Based Poly(Ionic Liquid)s Featuring Acetate Counter Anions: Thermally Latent and Recyclable Precursors of Polymer-Supported N-Heterocyclic Carbenes for Organocatalysis. AB - Statistical copoly(ionic liquid)s (coPILs), namely, poly(styrene)-co-poly(4 vinylbenzylethylimidazolium acetate) are synthesized by free-radical copolymerization in methanolic solution. These coPILs serve to in situ generate polymer-supported N-heterocyclic carbenes (NHCs), referred to as polyNHCs, due to the noninnocent role of the weakly basic acetate counter-anion interacting with the proton in C2-position of pendant imidazolium rings. Formation of polyNHCs is first evidenced through the quantitative formation of NHC-CS2 units by chemical postmodification of acetate-containing coPILs, in the presence of CS2 as electrophilic reagent (= stoichiometric functionalization of polyNHCs). The same coPILs are also employed as masked precursors of polyNHCs in organocatalyzed reactions, including a one-pot two-step sequential reaction involving benzoin condensation followed by addition of methyl acrylate, cyanosilylation, and transesterification reactions. The catalytic activity can be switched on and off successively upon thermal activation, thanks to the deprotonation/reprotonation equilibrium in C2-position. NHC species are thus in situ released upon heating at 80 degrees C (deprotonation), while regeneration of the coPIL precursor occurs at room temperature (reprotonation), triggering its precipitation in tetrahydrofuran. This also allows recycling the coPIL precatalyst by simple filtration, and reusing it for further catalytic cycles. The different organocatalyzed reactions tested can thus be performed with excellent yields after several cycles. PMID- 26991792 TI - Lung function in sickle cell disease: An elusive relationship. PMID- 26991793 TI - Steroid Avoidance or Withdrawal Regimens in Paediatric Kidney Transplantation: A Meta-Analysis of Randomised Controlled Trials. AB - BACKGROUND: We combined the outcomes of all randomised controlled trials to investigate the safety and efficacy of steroid avoidance or withdrawal (SAW) regimens in paediatric kidney transplantation compared with steroid-based (SB) regimens. METHODS: A systematic literature search of PubMed, Embase, Cochrane Library, the trials registry and BIOSIS previews was performed. A change in the height standardised Z-score from baseline (DeltaHSDS) and acute rejection were the primary endpoints. RESULTS: Eight reports from 5 randomised controlled trials were included, with a total of 528 patients. Sufficient evidence of a significant increase in the DeltaHSDS was observed in the SAW group (mean difference (MD) = 0.38, 95% confidence interval (CI) 0.07-0.68, P = 0.01), particularly within the first year post-withdrawal (MD = 0.22, 95% CI 0.10-0.35, P = 0.0003) and in the prepubertal recipients (MD = 0.60, 95% CI 0.21-0.98, P = 0.002). There was no significant difference in the risk of acute rejection between the groups (relative risk = 1.04, 95% CI 0.80-1.36, P = 0.77). CONCLUSIONS: The SAW regimen is justified in select paediatric renal allograft recipients because it provides significant benefits in post-transplant growth within the first year post withdrawal with minimal effects on the risk of acute rejection, graft function, and graft and patient survival within 3 years post-withdrawal. These select paediatric recipients should have the following characteristics: prepubertal; Caucasian; with primary disease not related to immunological factors; de novo kidney transplant recipient; with low panel reactive antibody. PMID- 26991796 TI - Stabilization of a Tetrahedral (Mn(5+)O4) Chromophore in Ternary Barium Oxides as a Strategy toward Development of New Turquoise/Green-Colored Pigments. AB - An experimental investigation of the stabilization of the turquoise-colored chromophore Mn(5+)O4 in various oxide hosts, viz., A3(VO4)2 (A = Ba, Sr, Ca), YVO4, and Ba2MO4 (M = Ti, Si), has been carried out. The results reveal that substitution of Mn(5+)O4 occurs in Ba3(VO4)2 forming the entire solid solution series Ba3(V1-xMnxO4)2 (0 < x <= 1.0), while with the corresponding strontium derivative, only up to about 10% of Mn(5+)O4 substitution is possible. Ca3(VO4)2 and YVO4 do not stabilize Mn(5+)O4 at all. With Ba2MO4 (M = Ti, Si), we could prepare only partially substituted materials, Ba2M1-xMn(5+)xO4+x/2 for x up to 0.15, that are turquoise-colored. We rationalize the results that a large stabilization of the O 2p-valence band states occurs in the presence of the electropositive barium that renders the Mn(5+) oxidation state accessible in oxoanion compounds containing PO4(3-), VO4(3-), etc. By way of proof-of-concept, we synthesized new turquoise-colored Mn(5+)O4 materials, Ba5(BO3)(MnO4)2Cl and Ba5(BO3)(PO4)(MnO4)Cl, based on the apatite-Ba5(PO4)3Cl-structure. PMID- 26991795 TI - Neither Basic Life Support knowledge nor self-efficacy are predictive of skills among dental students. AB - AIM: Basic life support (BLS) is considered a core competence for the graduating dentist. This study aimed to measure BLS knowledge, self-efficacy and skills of undergraduate dental students in Dublin. METHODS: This study consisted of a cross sectional survey measuring BLS knowledge and self-efficacy, accompanied by a directly observed BLS skills assessment in a subsample of respondents. Data were collected in January 2014. Bivariate correlations between descriptive and outcome variables (knowledge, self-efficacy and skills) were tested using Pearson's chi square. We included knowledge and self-efficacy as predictor variables, along with other variables showing association, into a binary logistic regression model with BLS skills as the outcome measure. RESULTS: One hundred and thirty-five students participated. Almost all (n = 133, 98.5%) participants had BLS training within the last 2 years. One hundred and four (77%) felt that they were capable of providing effective BLS (self-efficacy), whilst only 46 (34.1%) scored >80% of knowledge items correct. Amongst the skills (n = 85) subsample, 38.8% (n = 33) were found to pass the BLS skills assessment. Controlling for gender, age and skills assessor, the regression model did not identify a predictive relationship between knowledge or self-efficacy and BLS skills. CONCLUSIONS: Neither knowledge nor self-efficacy was predictive of BLS skills. Dental students had low levels of knowledge and skills in BLS. Despite this, their confidence in their ability to perform BLS was high and did not predict actual competence. There is a need for additional hands-on training, focusing on self-efficacy and BLS skills, particularly the use of AED. PMID- 26991794 TI - Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug-induced liver injury case-control study in Italy. AB - AIM: Drug-induced liver injury is one of the most serious adverse drug reactions and the most frequent reason for restriction of indications or withdrawal of drugs. Some nonsteroidal anti-inflammatory drugs (NSAIDs) were withdrawn from the market because of serious hepatotoxicity. We estimated the risk of acute and serious liver injury associated with the use of nimesulide and other NSAIDs, with a prevalence of use greater than or equal to 5%. METHODS: This is a multicentre case-control study carried out in nine Italian hospitals from October 2010 to January 2014. Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders not related to chronic conditions, not involving the liver. Adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated initially with a bivariate and then multivariate analysis. RESULTS: We included 179 cases matched to 1770 controls. Adjusted OR for acute serious liver injury associated with all NSAIDs was 1.69, 95% CI 1.21-2.37. Thirty cases were exposed to nimesulide (adjusted OR 2.10, 95% CI 1.28-3.47); the risk increased according to the length of exposure (OR > 30 days: 12.55, 95% CI 1.73-90.88) and to higher doses (OR 10.69, 95% CI 4.02-28.44). Risk of hepatotoxicity was increased also for ibuprofen, used both at recommended dosages (OR 1.92, 95% CI 1.13-3.26) and at higher doses (OR 3.73, 95% CI 1.11-12.46) and for ketoprofen >= 150 mg (OR 4.65, 95% CI 1.33-10.00). CONCLUSION: Among all NSAIDs, nimesulide is associated with the higher risk, ibuprofen and high doses of ketoprofen are also associated with a modestly increased risk of hepatotoxicity. PMID- 26991797 TI - Propranolol for infantile hemangioma: Effect on plasma vascular endothelial growth factor. AB - BACKGROUND: Propranolol has recently been shown to be highly effective for infantile hemangioma (IH), but the mechanism of action of propranolol and the usefulness of measurement of vascular endothelial growth factor (VEGF) remain poorly understood. The aim of this study was therefore to determine the efficacy of propranolol treatment and to evaluate changes in plasma VEGF in IH patients who underwent propranolol treatment. METHODS: The study group consisted of 35 children with IH. Oral propranolol was give at a dose of 2.0 mg/kg/day and was divided in three doses. Outcome was assessed using the visual analog scale (VAS) of size and color. Plasma VEGF concentration was analyzed on enzyme-linked immunoabsorbent assay, and compared between the groups. RESULTS: Improvement in VAS in patients who started propranolol before 6 months of age was superior to that in those who started propranolol after 6 months of age. VEGF concentration was significantly correlated with lesion size (P = 0.002), whereas no correlation was observed with age. VEGF concentration 4 weeks after treatment was significantly lower than that before treatment (P < 0.01). CONCLUSIONS: Measurement of VEGF may be a useful tool for predicting the course of IH and monitoring the effectiveness of treatment. PMID- 26991798 TI - Comparison of intravascular optical frequency domain imaging versus intravascular ultrasound during balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. AB - OBJECTIVES: The aims of this study are (1) to evaluate the safety and feasibility of using optical frequency domain imaging (OFDI) during balloon pulmonary angioplasty (BPA) procedures, (2) to assess the correlations between the vessel area (VA) and luminal area (LA) obtained by OFDI and intravascular ultrasound (IVUS), and (3) to compare inter- and intra-observer variability among measurements taken from OFDI and IVUS images. BACKGROUND: The BPA in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is an evolving procedure. METHODS: Twenty-three consecutive attempts of pair of OFDI and IVUS during BPA were evaluated. All complications that occurred during-BPA and up to 48 hr post-BPA were recorded. Using side branches as landmarks, 48 pairs of regions were chosen to compare measurements of VA and LA. RESULTS: OFDI images can be obtained without any procedurally related complications. Although the VA and LA measurements obtained by OFDI were smaller than those obtained by IVUS, high correlations were found (VA: r = 0.78, P < 0.0001 and LA: r = 0.75, P < 0.0001). Less inter- and intra-observer variability was found when using measurements taken from OFDI versus IVUS images. CONCLUSIONS: OFDI during BPA was safe and feasible. The reproducibility of OFDI imaging was excellent and offered a favorable addition to the BPA procedures. (c) 2016 The Authors Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc. PMID- 26991799 TI - Immunoexpression of hoxb7 and hoxb9 in salivary gland tumours. AB - BACKGROUND: Salivary gland carcinomas are uncommon neoplasms and the identification of new prognostic indicators could improve their management. HOXB7 and HOXB9 are members of the class I homeobox-containing genes important for normal embryogenesis and that are dysregulated in several human neoplasms. This study investigated HOXB7 and HOXB9 expressions in salivary gland tumourigenesis, their correlation with neoplastic proliferative and angiogenic features and their importance as prognostic markers. METHODS: A hundred and fifty salivary gland tumours were organized in tissue microarray and expressions of CD105, Ki67, HOXB7 and HOXB9 were determined through immunohistochemistry. Reactions were quantified and correlated with clinicopathological parameters. RESULTS: In normal glands, HOXB7 was found in basal cells, whereas HOXB9 was seen in serous acinar and scattered ductal cells. Malignancies exhibited an increased vascular density, proliferative index, HOXB7 and HOXB9 expressions when compared with pleomorphic adenoma and Warthin's tumour. Significant correlation was found between HOXB7 and CD105 (P = 0.004) in adenoid cystic carcinomas, and HOXB7 higher expression significantly correlated with the presence of paresthesia (P = 0.02). No marker exhibited a significant association with survival rates (P > 0.05). CONCLUSION: HOXB7 and HOXB9 were expressed in normal salivary gland and were present in benign and malignant tumours derived from these structures, and HOXB7 significantly correlated with neoangiogenesis in AdCC. These findings suggest that both proteins might play a role in salivary gland tumourigenesis, but they were not significant prognostic determinants in this sample. PMID- 26991800 TI - Roles of the Laodelphax striatellus Down syndrome cell adhesion molecule in Rice stripe virus infection of its insect vector. AB - The arthropod Down syndrome cell adhesion molecule (Dscam) mediates pathogen specific recognition via an extensive protein isoform repertoire produced by alternative splicing. To date, most studies have focused on the subsequent pathogen-specific immune response, and few have investigated the entry into cells of viruses or endosymbionts. In the present study, we cloned and characterized the cDNA of Laodelphax striatellus Dscam (LsDscam) and investigated the function of LsDscam in rice stripe virus (RSV) infection and the influence on the endosymbiont Wolbachia. LsDscam displayed a typical Dscam domain architecture, including 10 immunoglobulin (Ig) domains, six fibronectin type III domains, one transmembrane domain and a cytoplasmic tail. Alternative splicing occurred at the N-termini of the Ig2 and Ig3 domains, the complete Ig7 domain, the transmembrane domain and the C-terminus, comprising 10, 51, 35, two and two variable exons, respectively. Potentially LsDscam could encode at least 71 400 unique isoforms and 17 850 types of extracellular regions. LsDscam was expressed in various L. striatellus tissues. Knockdown of LsDscam mRNA via RNA interference decreased the titres of both RSV and Wolbachia, but did not change the numbers of the extracellular symbiotic bacterium Acinetobacter rhizosphaerae. Specific Dscam isoforms may play roles in enhancing the infection of vector-borne viruses or endosymbionts. PMID- 26991802 TI - Current Status of Malignant Neuropathic Pain in Chinese Patients with Cancer: Report of a Hospital-based Investigation of Prevalence, Etiology, Assessment, and Treatment. AB - OBJECTIVES: This study investigated the prevalence, etiology, assessment, treatment of pain in patients with cancer as well as their quality of life (QOL). METHODS: Patients at the West China Hospital Cancer Center were invited to complete a questionnaire under the guidance of pain specialists. The questionnaire included general information, cancer pain status, its assessment, use of analgesics, and the effects of pain on QOL. RESULTS: In total, 1,050 patients were enrolled in the study. Of these, valid data were collected from 919 patients, among whom 454 (49.4%) suffered from pain, including 333 (36.2%) patients who had neuropathic pain symptoms. On average, the visual analog scale (VAS) score of patients with cancer pain was 3.30 +/- 1.68. Significant differences in the VAS score and pain frequency between patients with nociceptive and neuropathic pain were observed (both P < 0.05). Dull pain ranked first (64, 52.9%) among the patients with nociceptive pain, whereas pins and needles pain (97, 64.7%) was the most common type of pain in patients with neuropathic pain. There was a significant difference in QOL between the nociceptive and neuropathic pain groups (P < 0.05). Only 183 of 454 patients with cancer pain used analgesics. Compared with the patients with pain not using any analgesics, those receiving analgesics had a significantly lower average pain relief rate (P = 0.027). Adjuvant analgesics were inadequately used (9.3%) in patients with neuropathic cancer pain. CONCLUSION: This study revealed the prevalence of neuropathic cancer pain in Chinese patients with cancer. Malignant neuropathic pain significantly impaired the patients' QOL. Insufficient assessment and inadequate analgesia still exist. These require more awareness and attention from both doctors and patients. PMID- 26991801 TI - Epigenetics Reactivation of Nrf2 in Prostate TRAMP C1 Cells by Curcumin Analogue FN1. AB - It has previously been shown that curcumin can effectively inhibit prostate cancer proliferation and progression in TRAMP mice, potentially acting through the hypomethylation of the Nrf2 gene promoter and hence activation of the Nrf2 pathway to enhance cell antioxidative defense. FN1 is a synthetic curcumin analogue that shows stronger anticancer activity than curcumin in other reports. We aimed to explore the epigenetic modification of FN1 that restores Nrf2 expression in TRAMP-C1 cells. Stably transfected HepG2-C8 cells were used to investigate the effect of FN1 on the Nrf2- antioxidant response element (ARE) pathway. Real-time quantitative PCR and Western blotting were applied to study the influence of FN1 on endogenous Nrf2 and its downstream genes. Bisulfite genomic sequencing (BGS) and methylated DNA immunoprecipitation (MeDIP) were then performed to examine the methylation profile of the Nrf2 promoter. An anchorage independent colony-formation analysis was conducted to examine the tumor inhibition activity of FN1. Epigenetic modification enzymes, including DNMTs and HDACs, were investigated by Western blotting. The luciferase reporter assay indicated that FN1 was more potent than curcumin in activating the Nrf2-ARE pathway. FN1 increased the expression of Nrf2 and its downstream detoxifying enzymes. FN1 significantly inhibited the colony formation of TRAMP-C1 cells. BGS and MeDIP assays revealed that FN1 treatment (250 nM for 3 days) reduced the percentage of CpG methylation of the Nrf2 promoter. FN1 also downregulated epigenetic modification enzymes. In conclusion, our results suggest that FN1 is a novel anticancer agent for prostate cancer. In the TRAMP-C1 cell line, FN1 can increase the level of Nrf2 and downstream genes via activating the Nrf2-ARE pathway and inhibit the colony formation potentially through the decreased expression of keap1 coupled with CpG demethylation of the Nrf2 promoter. This CpG demethylation effect may come from decreased epigenetic modification enzymes, such as DNMT1, DNMT3a, DNMT3b, and HDAC4. PMID- 26991803 TI - MR thermometry near metallic devices using multispectral imaging. AB - PURPOSE: The lack of a technique for MR thermometry near metal excludes a growing patient population from promising treatments such as MR-guided focused ultrasound therapy. Here we explore the feasibility of multispectral imaging (MSI) for noninvasive temperature measurement in the presence of strong field inhomogeneities by exploiting the temperature dependency of the T1 relaxation time. METHODS: A two-dimensional inversion-recovery-prepared MSI pulse sequence (2DMSI) was implemented for artifact-reduced T1 mapping near metal. A series of T1 maps was acquired in a metallic implant phantom while increasing the phantom temperature. The measured change in T1 was analyzed with respect to the phantom temperature. For comparison, proton resonance frequency shift (PRFS) thermometry was performed. RESULTS: 2DMSI achieved artifact-reduced, single-slice T1 mapping in the presence of strong off-resonance with a spatial resolution of 1.9 mm in plane and a temporal resolution of 5 min. The maps enabled temperature measurements over a range of 30 degrees C with an uncertainty below 1.4 degrees C. The quality of the resulting temperature maps was independent of the distance from the metal, whereas the PRFS-based temperature measurements were increasingly impaired with increasing off-resonance. CONCLUSION: We demonstrated the ability to noninvasively measure temperature near metal using MSI and the T1 temperature sensitivity. Magn Reson Med 77:1162-1169, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26991805 TI - Advanced endoscopic therapy in inflammatory bowel disease. PMID- 26991804 TI - IgE Inhibits Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Expression of Interferon-alpha by Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus. AB - OBJECTIVE: Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNalpha secretion. These receptors use the gamma-chain of high-affinity Fc receptor (FcR) for IgE, FcERI. We undertook this study to test our hypothesis that IgE engagement of FcERI on PDCs may impact IFNalpha production in SLE patients. METHODS: Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcERI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNalpha production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR. RESULTS: We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcERI expression in an IgE dose-dependent manner. IgE-treated PDCs significantly decreased IFNalpha secretion and down regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7. CONCLUSION: Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs. PMID- 26991806 TI - Pulmonary vein triggers, focal sources, rotors and atrial cardiomyopathy: implications for the choice of the most effective ablation therapy. AB - Understanding of the pathophysiological mechanism(s) underlying atrial fibrillation (AF) is the foundation on which current ablation strategies are built. In the vast majority of patients with paroxysmal AF, the ablation procedure should target the pulmonary veins. In patients with nonparoxysmal AF, however, pulmonary vein isolation alone seems to be insufficient to prevent the arrhythmia. Several recent clinical trials have investigated the concept that rotors (re-entry based on a meandering central core from which spiral waves emanate) might be the mechanism responsible for sustaining AF. Ablation of these localized AF sources is an important step towards substrate-driven procedures in persistent AF. Hybrid AF ablation procedures, based on the integration of endocardial transcatheter and epicardial off-pump surgical techniques, have been introduced to overcome their mutual shortcomings. The long-term results are encouraging, especially in currently challenging settings such as nonparoxysmal AF and failed endocardial catheter ablation procedures. PMID- 26991808 TI - Biogeographic bases for a shift in crop C : N : P stoichiometries during domestication. AB - We lack both a theoretical framework and solid empirical data to understand domestication impacts on plant chemistry. We hypothesised that domestication increased leaf N and P to support high plant production rates, but biogeographic and climate patterns further influenced the magnitude and direction of changes in specific aspects of chemistry and stoichiometry. To test these hypotheses, we used a data set of leaf C, N and P from 21 herbaceous crops and their wild progenitors. Domestication increased leaf N and/or P for 57% of the crops. Moreover, the latitude of the domestication sites (negatively related to temperature) modulated the domestication effects on P (+), C (-), N : P (-) and C : P (-) ratios. Further results from a litter decomposition assay showed that domestication effects on litter chemistry affected the availability of soil N and P. Our findings draw attention to evolutionary effects of domestication legacies on plant and soil stoichiometry and related ecosystem services (e.g. plant yield and soil fertility). PMID- 26991807 TI - Caring for caregivers and patients: Research and clinical priorities for informal cancer caregiving. AB - Informal/family caregivers are a fundamental source of care for cancer patients in the United States, yet the population of caregivers and their tasks, psychosocial needs, and health outcomes are not well understood. Changes in the nature of cancer care and its delivery, along with the growing population of survivors and their caregivers, warrant increased attention to the roles and demands of caregiving. This article reviews current evidence presented at a 2-day meeting examining the state of the science of informal cancer caregiving that was convened by the National Cancer Institute and the National Institute of Nursing Research. The meeting sought to define who is an informal cancer caregiver, summarize the state of the science in informal cancer caregiving, and describe both the kinds of interventions developed to address caregiving challenges and the various outcomes used to evaluate their impact. This article offers recommendations for moving science forward in 4 areas: 1) improving the estimation of the prevalence and burden of informal cancer caregiving; 2) advancing the development of interventions designed to improve outcomes for cancer patients, caregivers, and patient-caregiver dyads; 3) generating and testing strategies for integrating caregivers into formal health care settings; and 4) promoting the use of technology to support informal cancer caregivers. Cancer 2016;122:1987-95. (c) 2016 American Cancer Society. PMID- 26991809 TI - Antibody responses following incident anal and penile infection with human papillomavirus in teenage men who have sex with men. AB - Men who have sex with men (MSM) are at risk for human papillomavirus (HPV) related anal cancer. Few data exist on antibody responses following incident anogenital infection with HPV in teenage MSM. A cohort of 200 MSM aged 16-20 years from Melbourne, Australia were assessed at baseline, 3, 6 and 12 months. At each visit anal and penile swabs were collected for HPV DNA and serum for HPV antibodies for genotypes 6, 11, 16 and 18 (Merck's Multiplex Assays using Luminex). The main outcome, seroconversion, was defined as the detection of HPV antibodies following a negative antibody result for the same HPV type at baseline. The seroincidence rates for HPV types 6, 11, 16 and 18 were: 19 (95% CI 12-26), 7 (3-12), 4 (1-8) and 6 (3-11) per 100 person-years, respectively. Men who experienced incident anal HPV infections from types 6/11 were significantly more likely to develop serum antibodies to the same HPV type(s) than those who experienced incident anal infections from types 16/18 [73 vs. 18%, odds ratio (OR) = 15, 95% CI: 2-118]. The median time between incident anal HPV infection and seroconversion for HPV 6, 11, 16 and 18 was: 91, 38, 161 and 182 days, respectively. Antibody responses against HPV types 6/11 were significantly more likely to occur following incident anal compared with incident penile infection with HPV types 6/11 (OR = 6, 95% CI: 2-21). The likelihood of antibody responses following anogenital HPV infections depends on the HPV type and site of infection. PMID- 26991810 TI - Evaluation of Fibrosis Markers: Apelin and Transforming Growth Factor-beta1 in Autosomal Dominant Polycystic Kidney Disease Patients. AB - Renal interstitial fibrosis is an important pathological feature of autosomal dominant polycystic kidney disease (ADPKD), which progressively develops to end stage renal disease (ESRD). It has been shown that apelin and transforming growth factor-beta1 (TGF-beta1) play important roles in the renal fibrosis process. The aim of the present study is to evaluate the relationship of these fibrosis markers and ADPKD. Forty-five patients with ADPKD and 28 healthy controls were studied cross-sectionally. Estimated glomerular filtration rate (eGFR), apelin, TGF-beta1 were measured in all participants, using conventional methods. Apelin levels were lower (1.2 +/- 0.9 ng/mL vs. 2.5 +/- 1.3 ng/mL, P < 0.001), while TGF-beta1 levels were higher in the patient group according to healthy controls (466.5 +/- 200.5 ng/L vs. 367.1 +/- 163.45 ng/L, P = 0.031), respectively. Apelin was negatively correlated with TGF-beta1 and highly sensitive C-reactive protein (hs-CRP); and positively correlated with eGFR. In all subjects, eGFR was independently predicted by TGF-beta1 and apelin. Apelin and TGF-beta1 may be used as biomarkers of renal fibrosis that is an important pathological feature of ADPKD, which progressively develops to ESRD in ADPKD patients. PMID- 26991811 TI - Reply. PMID- 26991812 TI - Extremely low-frequency magnetic fields and risk of childhood leukemia: A risk assessment by the ARIMMORA consortium. AB - Exposure to extremely low-frequency magnetic fields (ELF-MF) was evaluated in an International Agency for Research on Cancer (IARC) Monographs as "possibly carcinogenic to humans" in 2001, based on increased childhood leukemia risk observed in epidemiological studies. We conducted a hazard assessment using available scientific evidence published before March 2015, with inclusion of new research findings from the Advanced Research on Interaction Mechanisms of electroMagnetic exposures with Organisms for Risk Assessment (ARIMMORA) project. The IARC Monograph evaluation scheme was applied to hazard identification. In ARIMMORA for the first time, a transgenic mouse model was used to mimic the most common childhood leukemia: new pathogenic mechanisms were indicated, but more data are needed to draw definitive conclusions. Although experiments in different animal strains showed exposure-related decreases of CD8+ T-cells, a role in carcinogenesis must be further established. No direct damage of DNA by exposure was observed. Overall in the literature, there is limited evidence of carcinogenicity in humans and inadequate evidence of carcinogenicity in experimental animals, with only weak supporting evidence from mechanistic studies. New exposure data from ARIMMORA confirmed that if the association is nevertheless causal, up to 2% of childhood leukemias in Europe, as previously estimated, may be attributable to ELF-MF. In summary, ARIMMORA concludes that the relationship between ELF-MF and childhood leukemia remains consistent with possible carcinogenicity in humans. While this scientific uncertainty is dissatisfactory for science and public health, new mechanistic insight from ARIMMORA experiments points to future research that could provide a step-change in future assessments. Bioelectromagnetics. 37:183-189, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991813 TI - Cost utility analysis of endoscopic sinus surgery for chronic rhinosinusitis. AB - BACKGROUND: The purpose of this work was to evaluate the cost-effectiveness of endoscopic sinus surgery (ESS) compared to medical therapy for patients with chronic rhinosinusitis (CRS). METHODS: The study design consisted of a microsimulation Markov decision-tree economic model with a 31-year time horizon. A cohort of 489 patients who underwent ESS for CRS were matched 1 to 1 with a cohort of 489 patients from the national Medical Expenditures Panel Survey database who underwent medical management for CRS. Utility scores were calculated from responses to the EuroQol 5-Dimension instrument in both cohorts. Decision tree analysis and a subsequent 10-state Markov model utilized published event probabilities as well as primary data from a large multisurgeon prospective outcomes study to calculate long-term costs and utility. The primary outcome measure was incremental cost per quality-adjusted life year (QALY). Multiple sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) for ESS vs medical therapy alone was $13,851.26 per QALY. The cost effectiveness acceptability curve demonstrated 85.84% and 98.69% certainty that the ESS strategy was the most cost-effective option at willingness-to-pay thresholds of $25,000 and $50,000 per QALY, respectively. CONCLUSION: This study shows ESS to be a cost-effective intervention compared to medical therapy alone for the management of patients with CRS. PMID- 26991815 TI - Is the Framework of Cohn's 'Tritope Model' for How T Cell Receptors Recognize Peptide/Self-MHC Complexes and Allo-MHC Plausible? AB - Cohn has developed the tritope model to describe how distinct domains of the T cell receptor (TcR) recognize peptide/self-MHC complexes and allo-MHC. He has over the years employed this model as a framework for considering how the TcR might mediate various signals [1-5]. In a recent publication [5], Cohn employs the Tritope Model to propose a detailed mechanism for the T cell receptor's involvement in positive thymic selection [5]. During a review of this proposal, I became uneasy over the plausibility of the underlying framework of the Tritope Model. I outline here the evolutionary considerations making me question this framework. I also suggest that the proposed framework underlying the Tritope Model makes strong predictions whose validity can most probably be assessed by considering observations reported in the literature. PMID- 26991814 TI - The impact of continued intervention on weight: Five-year results from the weight loss maintenance trial. AB - OBJECTIVE: In the Weight Loss Maintenance (WLM) Trial, a personal contact (PC) intervention sustained greater weight loss relative to a self-directed (SD) group over 30 months. This study investigated the effects of continued intervention over an additional 30 months and overall weight change across the entire WLM Trial. METHODS: WLM had 3 phases. Phase 1 was a 6-month weight loss program. In Phase 2, those who lost >=4 kg were randomized to a 30-month maintenance trial. In Phase 3, PC participants (n = 196, three sites) were re-randomized to no further intervention (PC-Control) or continued intervention (PC-Active) for 30 more months; 218 SD participants were also followed. RESULTS: During Phase 3, weight increased 1.0 kg in PC-Active and 0.5 kg in PC-Control (mean difference 0.6 kg; 95% CI:-1.4 to 2.7; P = 0.54). Mean weight change over the entire study was -3.2 kg in those originally assigned to PC (PC-Combined) and -1.6 kg in SD (mean difference -1.6 kg; 95% CI:-3.0 to -0.1; P = 0.04). CONCLUSIONS: After 30 months of the PC maintenance intervention, continuation for another 30 months provided no additional benefit. However, across the entire study, weight loss was slightly greater in those originally assigned to PC. PMID- 26991816 TI - Characterization of Staphylococcus aureus faecal isolates associated with food borne disease in Korea. AB - AIMS: To characterize Staphylococcus aureus faecal isolates from people suspected to be infected with food poisoning by using antimicrobial susceptibility testing and molecular techniques. METHODS AND RESULTS: A total of 340 Staph. aureus isolates from 6226 people suspected to be infected with food poisoning were identified and characterized by biochemical methods, antimicrobial susceptibility testing and PCR. Samples were obtained from January 2006 to December 2008 from the National Notifiable Diseases Surveillance System at the Research Institute of Public Health and Environment in Seoul Metropolitan, Korea. All strains carried at least one of the eight staphylococcal enterotoxin (se) genes tested and a total of 27 se profiles were produced; the most frequent se profile was seg-sei and the next was sea. Among the total isolates, 36 methicillin-resistant Staphylococcus aureus (MRSAs) isolates were further analysed by multilocus sequence typing (MLST), Staphylococcal cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE) and PCR detection for pvl. ST72-SCCmec type IV was the most predominant clone (27 isolates, 75%) followed by ST1-SCCmec type IV (five isolates, 13.8%), ST20-SCCmec type IV (one isolate, 2.8%), ST493 SCCmec type IV (one isolate, 2.8%), ST903-SCCmec type IV (one isolate, 2.8%) and ST5-SCCmec type II (one isolate, 2.8%). By PFGE typing, MRSAs isolated during the same period were grouped together although they were isolated from different regions. None of MRSAs had PVL gene and nine MRSAs were multidrug resistant. CONCLUSIONS: Analysis of MRSAs by MLST, SCCmec typing, PFGE and pvl detection showed that the majority of strain associated with food-borne diseases belonged to a Korean community-acquired (CA) MRSA clone with ST72-SCCmec type IV-PVL negative-SEG/SEI and its variations while one strain was hospital-acquired (HA) MRSA. SIGNIFICANCE AND IMPACT OF THE STUDY: CA-MRSA clone which possessed ST72 SCCmec type IV-PVL negative-SEG/SEI was spread most commonly among MRSAs that were associated with food-borne diseases. This is the first report of ST903 strain in Korea. PMID- 26991817 TI - Low-dose radiation prevents type 1 diabetes-induced cardiomyopathy via activation of AKT mediated anti-apoptotic and anti-oxidant effects. AB - We investigated whether low-dose radiation (LDR) can prevent late-stage diabetic cardiomyopathy and whether this protection is because of the induction of anti apoptotic and anti-oxidant pathways. Streptozotocin-induced diabetic C57BL/6J mice were treated with/without whole-body LDR (12.5, 25, or 50 mGy) every 2 days. Twelve weeks after onset of diabetes, cardiomyopathy was diagnosed characterized by significant cardiac dysfunction, hypertrophy and histopathological abnormalities associated with increased oxidative stress and apoptosis, which was prevented by LDR (25 or 50 mGy only). Low-dose radiation-induced cardiac protection also associated with P53 inactivation, enhanced Nrf2 function and improved Akt activation. Next, for the mechanistic study, mouse primary cardiomyocytes were treated with high glucose (33 mmol/l) for 24 hrs and during the last 15 hrs bovine serum albumin-conjugated palmitate (62.5 MUmol/l) was added into the medium to mimic diabetes, and cells were treated with LDR (25 mGy) every 6 hrs during the whole process of HG/Pal treatment. Data show that blocking Akt/MDM2/P53 or Akt/Nrf2 pathways with small interfering RNA of akt, mdm2 and nrf2 not only prevented LDR-induced anti-apoptotic and anti-oxidant effects but also prevented LDR-induced suppression on cardiomyocyte hypertrophy and fibrosis against HG/Pal. Low-dose radiation prevented diabetic cardiomyopathy by improving cardiac function and hypertrophic remodelling attributed to Akt/MDM2/P53-mediated anti-apoptotic and Akt/Nrf2-mediated anti-oxidant pathways simultaneously. PMID- 26991819 TI - Characterization of multiciliated ependymal cells that emerge in the neurogenic niche of the aged zebrafish brain. AB - In mammals, ventricular walls of the developing brain maintain a neurogenic niche, in which radial glial cells act as neural stem cells (NSCs) and generate new neurons in the embryo. In the adult brain, the neurogenic niche is maintained in the ventricular-subventricular zone (V-SVZ) of the lateral wall of lateral ventricles and the hippocampal dentate gyrus. In the neonatal V-SVZ, radial glial cells transform into astrocytic postnatal NSCs and multiciliated ependymal cells. On the other hand, in zebrafish, radial glial cells continue to cover the surface of the adult telencephalic ventricle and maintain a higher neurogenic potential in the adult brain. However, the cell composition of the neurogenic niche of the aged zebrafish brain has not been investigated. Here we show that multiciliated ependymal cells emerge in the neurogenic niche of the aged zebrafish telencephalon. These multiciliated cells appear predominantly in the dorsal part of the ventral telencephalic ventricular zone, which also contains clusters of migrating new neurons. Scanning electron microscopy and live imaging analyses indicated that these multiple cilia beat coordinately and generate constant fluid flow within the ventral telencephalic ventricle. Analysis of the cell composition by transmission electron microscopy revealed that the neurogenic niche in the aged zebrafish contains different types of cells, with ultrastructures similar to those of ependymal cells, transit-amplifying cells, and migrating new neurons in postnatal mice. These data suggest that the transformation capacity of radial glial cells is conserved but that its timing is different between fish and mice. J. Comp. Neurol. 524:2982-2992, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991818 TI - The hypoxia-induced dehydrogenase HorA is required for coenzyme Q10 biosynthesis, azole sensitivity and virulence of Aspergillus fumigatus. AB - Aspergillus fumigatus is the predominant airborne pathogenic fungus causing invasive aspergillosis in immunocompromised patients. During infection A. fumigatus has to adapt to oxygen-limiting conditions in inflammatory or necrotic tissue. Previously, we identified a mitochondrial protein to be highly up regulated during hypoxic adaptation. Here, this protein was found to represent the novel oxidoreductase HorA. In Saccharomyces cerevisiae a homologue was shown to play a role in biosynthesis of coenzyme Q. Consistently, reduced coenzyme Q content in the generated DeltahorA mutant indicated a respective function in A. fumigatus. Since coenzyme Q is involved in cellular respiration and maintaining cellular redox homeostasis, the strain DeltahorA displayed an impaired response to both oxidative and reductive stress, a delay in germination and an accumulation of NADH. Moreover, an increased resistance against antifungal drugs was observed. All phenotypes were completely reversed by the addition of the synthetic electron carrier menadione. The deletion strain DeltahorA showed significantly attenuated virulence in two murine infection models of invasive pulmonary aspergillosis. Therefore, the biosynthesis of coenzyme Q and, particularly, the fungal-specific protein HorA play a crucial role in virulence of A. fumigatus. Due to its absence in mammals, HorA might represent a novel therapeutic target against fungal infections. PMID- 26991820 TI - Block Copolymerization of Lactide and an Epoxide Facilitated by a Redox Switchable Iron-Based Catalyst. AB - A cationic iron(III) complex was active for the polymerization of various epoxides, whereas the analogous neutral iron(II) complex was inactive. Cyclohexene oxide polymerization could be "switched off" upon in situ reduction of the iron(III) catalyst and "switched on" upon in situ oxidation, which is orthogonal to what was observed previously for lactide polymerization. Conducting copolymerization reactions in the presence of both monomers resulted in block copolymers whose identity can be controlled by the oxidation state of the catalyst: selective lactide polymerization was observed in the iron(II) oxidation state and selective epoxide polymerization was observed in the iron(III) oxidation state. Evidence for the formation of block copolymers was obtained from solubility differences, GPC, and DOSY-NMR studies. PMID- 26991821 TI - System Characterization of a Highly Integrated Preclinical Hybrid MPI-MRI Scanner. AB - Magnetic particle imaging (MPI) is a novel tracer-based in vivo imaging modality allowing quantitative measurements of the spatial distributions of superparamagnetic iron oxide (SPIO) nanoparticles in three dimensions (3D) and in real time using electromagnetic fields. However, MPI lacks the detection of morphological information which makes it difficult to unambiguously assign spatial SPIO distributions to actual organ structures. To compensate for this, a preclinical highly integrated hybrid system combining MPI and Magnetic Resonance Imaging (MRI) has been designed and gets characterized in this work. This hybrid MPI-MRI system offers a high grade of integration with respect to its hard- and software and enables sequential measurements of MPI and MRI within one seamless study and without the need for object repositioning. Therefore, time-resolved measurements of SPIO distributions acquired with MPI as well as morphological and functional information acquired with MRI can be combined with high spatial co registration accuracy. With this initial phantom study, the feasibility of a highly integrated MPI-MRI hybrid systems has been proven successfully. This will enable dual-modal in vivo preclinical investigations of mice and rats with high confidence of success, offering the unique feature of precise MPI FOV planning on the basis of MRI data and vice versa. PMID- 26991822 TI - Epidemiology of Chronic Low Back Pain in US Adults: Data From the 2009-2010 National Health and Nutrition Examination Survey. AB - OBJECTIVE: To describe the epidemiologic characteristics and associations with increased health care utilization in US adults with chronic low back pain (LBP). METHODS: The National Health and Nutrition Examination Survey 2009-2010 was administered to adults ages 20-69 years (n = 5,103). Chronic LBP was defined as pain in the area between the lower posterior margin of the rib cage and the horizontal gluteal fold, with a history of pain lasting almost every day for at least 3 months. Demographic and behavioral characteristics were compared between those with chronic LBP and those without. Factors associated with >=10 health care visits per year were evaluated in the chronic LBP subgroup (n = 700). RESULTS: Chronic LBP associations with adjusted odds ratios (ORadj ) >=2 included age 50-69 years, less than high school education, annual household income <$20,000, income from disability, depression, sleep disturbances, and medical comorbidities. Subjects with chronic LBP were more likely to be covered by government-sponsored insurance plans (ORadj 3.23 [95% confidence interval (95% CI) 2.19-4.75] for Medicaid and ORadj 2.25 [95% CI 1.57-3.22] for Medicare; P < 0.0001), and visited health care providers more frequently (ORadj 3.35 [95% CI 2.40-4.67] for >=10 health care visits in the past year; P < 0.0001). In the chronic LBP subgroup, adjusted ORs >=2 were found for associations between >=10 visits per year and unemployment, income from disability, depression, and sleep disturbances. CONCLUSION: US adults with chronic LBP are socioeconomically disadvantaged, make frequent health care visits, and are often covered by government-sponsored health insurance. The clustering of behavioral, psychosocial, and medical issues should be considered in the care of Americans with chronic LBP. PMID- 26991824 TI - Scanning Tunneling Microscopy and Spectroscopy of Air Exposure Effects on Molecular Beam Epitaxy Grown WSe2 Monolayers and Bilayers. AB - The effect of air exposure on 2H-WSe2/HOPG is determined via scanning tunneling microscopy (STM). WSe2 was grown by molecular beam epitaxy on highly oriented pyrolytic graphite (HOPG), and afterward, a Se adlayer was deposited in situ on WSe2/HOPG to prevent unintentional oxidation during transferring from the growth chamber to the STM chamber. After annealing at 773 K to remove the Se adlayer, STM images show that WSe2 layers nucleate at both step edges and terraces of the HOPG. Exposure to air for 1 week and 9 weeks caused air-induced adsorbates to be deposited on the WSe2 surface; however, the band gap of the terraces remained unaffected and nearly identical to those on decapped WSe2. The air-induced adsorbates can be removed by annealing at 523 K. In contrast to WSe2 terraces, air exposure caused the edges of the WSe2 to oxidize and form protrusions, resulting in a larger band gap in the scanning tunneling spectra compared to the terraces of air-exposed WSe2 monolayers. The preferential oxidation at the WSe2 edges compared to the terraces is likely the result of dangling edge bonds. In the absence of air exposure, the dangling edge bonds had a smaller band gap compared to the terraces and a shift of about 0.73 eV in the Fermi level toward the valence band. However, after air exposure, the band gap of the oxidized WSe2 edges became about 1.08 eV larger than that of the WSe2 terraces, resulting in the electronic passivation of the WSe2. PMID- 26991823 TI - Phase I study of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, in Japanese patients. AB - This phase I study in Japanese patients evaluated the safety, pharmacokinetics, and preliminary efficacy of palbociclib, a highly selective and reversible oral cyclin-dependent kinase 4/6 inhibitor, as monotherapy for solid tumors (part 1) and combined with letrozole as first-line treatment of postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2 negative advanced breast cancer (part 2). Part 1 evaluated palbociclib 100 and 125 mg once daily (3 weeks on/1 week off; n = 6 each group) to determine the maximum tolerated dose. Part 2 evaluated palbociclib maximum tolerated dose (125 mg) plus letrozole 2.5 mg (n = 6). The most common treatment-related adverse event was neutropenia (all grades/grade 3/4): 100 mg, 83%/67%; 125 mg, 67%/33%; and palbociclib plus letrozole, 100%/83%. Heavier pretreatment with chemotherapy may have resulted in higher neutropenia rates observed with the 100-mg dose. Palbociclib exposure was higher with 125 vs 100 mg (mean area under the plasma concentration-time curve over dosing interval [tau]: 1322 vs 547.5 ng.h/mL [single dose], 2838 vs 1276 ng.h/mL [multiple dose]; mean maximum plasma concentration: 104.1 vs 41.4 ng/mL [single dose], 185.5 vs 77.4 ng/mL [multiple dose]). Half-life was 23-26 h. No drug-drug interactions between palbociclib and letrozole occurred. Four patients had stable disease (>=24 weeks in one patient with rectal cancer [100 mg] and one with esophageal cancer [125 mg]) in part 1; two patients had partial response and two had stable disease (both >=24 weeks) in part 2. Palbociclib at the 125-mg dose (schedule 3/1) was tolerated and is the recommended dose for monotherapy and letrozole combination therapy in Japanese patients. The trials are registered with www.ClinicalTrials.gov: A5481010 and NCT01684215. PMID- 26991825 TI - HIV and Hepatitis Testing: Global Progress, Challenges, and Future Directions. AB - HIV infection and viral hepatitis due to HBV and HCV infection are major causes of chronic disease worldwide, and share some common routes of transmission, epidemiology, initial barriers faced in treatment access, and in strategies for a global public health response. Testing and diagnosis of HIV, HBV, and HCV infection is the gateway for access to both care and treatment and prevention services, and crucial for an effective HIV and hepatitis epidemic response. In this review article, we first summarize the common goals and guiding principles in a public health approach to HIV and hepatitis testing. We summarize the impressive global progress in HIV testing scale-up and evolution of approaches, with expansion of provider-initiated testing and counseling in clinical settings (particularly antenatal and tuberculosis clinics), the introduction of more community based testing services, and use of rapid diagnostic tests enabling provision of same-day test results. However, 46% of all people living with HIV are still unaware of their serostatus, and many continue to be diagnosed and start antiretroviral therapy late. As testing and treatment scale-up accelerates for an "treat all" approach, other challenges to address include how to better focus testing and reach those yet undiagnosed and most at risk, especially key populations, men, adolescents, and children. We summarize future directions in HIV testing to speed scale-up and close gaps that are addressed in the WHO 2015 consolidated HIV testing guidelines. In contrast to HIV, action in hepatitis testing and treatment has been fragmented and limited to a few countries, and there remains a large burden of undiagnosed cases globally. We summarize key challenges in the hepatitis testing response, including lack of simple, reliable, and low-cost diagnostic tests, laboratory capacity, and testing facilities; inadequate data to guide country specific hepatitis testing approaches and who to screen; stigmatization and social marginalization of those with or at risk of viral hepatitis; and lack of international or national guidelines on hepatitis testing for resource-limited settings. We highlight some of the key lessons applicable to hepatitis from the experience of expansion and diversification of HIV testing approaches over the last 30 years of the HIV response; in addition to forthcoming WHO tools to support the hepatitis global response. This includes a new 2016-2020 global hepatitis health sector strategy with testing and diagnosis targets, and 2016 WHO guidelines on hepatitis testing. PMID- 26991826 TI - NS5A Resistance: Clinical Implications and Treatment Possibilities. AB - Treatments with interferon-free direct-acting antiviral agents have high efficacy, with sustained virological response rates of more than 90%. Nevertheless, they fail to eliminate the infection in 1-7% of patients. The majority of virological failures are due to relapse following treatment discontinuation, while virological rebound during therapy is rare. Although not the only factor, the presence of resistance-associated variants is one of the major causes for said failure. Resistance-associated variants affect the sequence involved in protein synthesis on which different direct-acting antiviral agents act (NS3/4A, NS5A, NS5B). Of all these variants, the ones with the greatest impact are resistance-associated variants that affect the NS5A region due to their long-term persistence. In this article we will describe the most significant NS5A resistance-associated variants, the clinical relevance of their detection both before and after treatment, their persistence over time, and lastly, we will devote particular attention to discussing what approach to adopt when dealing with treatment failure to an antiviral regimen that includes NS5A inhibitors. PMID- 26991828 TI - Cytokeratin 18-based cell death markers indicate severity of liver disease and prognosis of cirrhotic patients. AB - BACKGROUND & AIMS: Hepatocyte death is an important factor in development and progression of cirrhosis. Cytokeratin 18-based serum markers reflecting apoptotic (M30) and overall epithelial cell death (M65 and M65EpiDeath) have been used as prognostic parameters for survival in patients with acute liver failure. However, there has been no trial investigating M30, M65 and M65EpiDeath as survival parameters in patients with cirrhosis and acute-on-chronic liver failure. METHODS: Patients with cirrhosis were enrolled and followed until death, liver transplantation or last contact. M30, M65 and M65EpiDeath serum levels were quantified in patient's sera. RESULTS: Three hundred and thirty-one patients were screened and 211 patients could be included in this study. The median duration of follow-up was 322 days with a range of 1-1382 days. All three cell death parameters correlated with the extent of the severity of the disease. However, M65EpiDeath was the only of the three parameters which was associated with the severe complications of cirrhosis including ascites, spontaneous bacterial peritonitis and hepatorenal syndrome. Additionally, M65EpiDeath was the only cell death parameter which was independently from liver function and its surrogate parameter such as Child-Pugh score and the model of end-stage liver disease associated with overall survival. CONCLUSIONS: Epithelial cell death reflected by M65EpiDeath serum levels is an indicator for the severity of cirrhosis and a prognostic survival parameter in cirrhotic patients. PMID- 26991829 TI - Obstructive sleep apnea in children with cerebral palsy and epilepsy. AB - AIM: To examine the risk of obstructive sleep apnea (OSA) in children with cerebral palsy (CP) and/or epilepsy. METHOD: This cross-sectional study employs the Pediatric Sleep Questionnaire (PSQ), the Gross Motor Function Classification System (GMFCS), and chart review to identify symptoms of OSA in children presenting to a multi-specialty pediatric healthcare institution. RESULTS: Two hundred and fifteen patients were grouped into those with epilepsy (n=54), CP (n=18), both (n=55), and neither (comparison group, n=88). The comparison group comprised children with developmental disabilities but not children with typical development. Significantly increased PSQ scores (indicating increased risk of OSA) were found among children with CP (58%) and CP with epilepsy (67%) than among the comparison group (27%; p<0.001 and p<0.0001 respectively). Children with both CP and epilepsy had a greater number of increased PSQ scores compared with CP alone (p<0.05). Increased PSQ scores were observed with increasing CP severity as measured using the GMFCS. The PSQ identified more children at risk of OSA (46%) than did the medical record review for symptoms of OSA (8.2%, p<0.001). INTERPRETATION: Children with CP of greater severity or comorbid epilepsy are at increased risk of OSA. This study supports the routine questionnaire-based assessment for OSA as a regular part of the care of all children with CP, especially in those with more severe CP and those with epilepsy. PMID- 26991827 TI - Intramuscular delivery of p75NTR ectodomain by an AAV vector attenuates cognitive deficits and Alzheimer's disease-like pathologies in APP/PS1 transgenic mice. AB - The neurotrophin receptor p75 (p75NTR) is a receptor for amyloid-beta (Abeta) and mediates Abeta-induced neurodegenerative signals. The ectodomain of p75NTR (p75ECD) is a physiological protective factor against Abeta in Alzheimer's disease (AD). We have previously demonstrated that the shedding of p75ECD from the cell surface is down-regulated in AD brains and restoration of the p75ECD level in the brain, through intracranial administration of p75ECD by adeno associated virus vectors, attenuates AD-like pathologies in an AD mouse model. In this study, we further investigated the feasibility and efficacy of peripheral administration of AAV-p75ECD on brain amyloid burden and associated pathogenesis. We found that intramuscular delivery of AAV-p75ECD increased the level of p75ECD in the blood, significantly improved the behavioral phenotype of amyloid precursor protein/PS1 transgenic mice, and reduced brain amyloid burden, attenuated Tau hyperphosphorylation, and neuroinflammation. Furthermore, intramuscular delivery of AAV-p75ECD was well tolerated. Our results indicate that peripheral delivery of p75ECD represents a safe and effective therapeutic strategy for AD. The ectodomain of p75NTR (p75ECD) is a physiological protective factor against amyloid-beta (Abeta) in Alzheimer's disease (AD). Intramuscular delivery of AAV-p75ECD increased the p75ECD levels in the blood, reduced brain amyloid burden through a 'peripheral sink' mechanism and alleviates AD-type pathologies. Peripheral delivery of p75ECD represents a promising therapeutic strategy for AD. PMID- 26991830 TI - Palladium-Catalyzed Carbonylative Four-Component Synthesis of Thiochromenones: The Advantages of a Reagent Capsule. AB - Multicomponent reactions, especially those involving four or even more reagents, have been a long-standing challenge because of the issues associated with balancing reactivity, selectivity, and compatibility. Herein, we demonstrate how the use of a reagent capsule provides straightforward access to synthetically valuable thiochromenone derivatives by a palladium-catalyzed carbonylative four component reaction. To the best of our knowledge, this is the first example of applying a capsule to prevent catalyst poisoning and undesired side reactions of the multicomponent reaction. PMID- 26991832 TI - miR-152 induces human dental pulp stem cell senescence by inhibiting SIRT7 expression. AB - Human dental pulp stem cells (HDPSCs) have potential applications in regenerative medicine. The molecular mechanisms underlying HDPSC senescence are not completely understood. Here, we investigated the significance of miR-152 in HDPSC senescence. We show that miR-152 is upregulated during HDPSC senescence and its overexpression in early passaged HDPSCs induced senescence. Sirtuin 7 (SIRT7) was identified as a target of miR-152. SIRT7 was downregulated in senescent HDPSCs, whereas miR-152 inhibition upregulated SIRT7 and suppressed the senescent phenotype and SIRT7 overexpression rescued miR-152-induced senescence. Our results demonstrate that the miR-152/SIRT7 axis plays a key role in the regulation of HDPSC senescence and provide a candidate target to improve the functional and therapeutic potential of HDPSCs. PMID- 26991833 TI - Luminescent ZnO quantum dots as an efficient sensor for free chlorine detection in water. AB - Highly luminescent ZnO quantum dots (QDs) synthesized via a simple and facile route are used for the preparation of an optical sensor for the detection of free chlorine. The concentration of free chlorine greatly affects the PL emission of the ZnO QDs at 525 nm. Since hypochlorite gains electrons with high efficiency, it takes electrons from the oxygen vacancies of ZnO QDs, which gives rise to defect emission in ZnO QDs. UV-vis data analysis shows that free chlorine does not affect the optical absorption spectra of ZnO QDs. The optical sensing of free chlorine using ZnO QDs has several advantages, like quick response time, good selectivity and of course high sensitivity. The pH has very little effect on the PL emission of ZnO QDs. It does not interfere in the sensing mechanism for free chlorine. After 60 s, the response of the ZnO QDs remains stable. The present sensor shows high selectivity with respect to various common cations, as well as anions. PMID- 26991831 TI - Spousal Characteristics and Older Adults' Hospice Use: Understanding Disparities in End-of-Life Care. AB - BACKGROUND: Hospice use has been shown to benefit quality of life for patients with terminal illness and their families, with further evidence of cost savings for Medicare and other payers. While disparities in hospice use by patient diagnosis, race, and region are well documented and attention to the role of family members in end-of-life decision-making is increasing, the influence of spousal characteristics on the decision to use hospice is unknown. OBJECTIVES: To determine the association between spousal characteristics and hospice use. DESIGN: We used data from the Health and Retirement Study (HRS), a prospective cohort study, linked to the Dartmouth Atlas of Health Care and Medicare claims. SETTING: National study of 1567 decedents who were married or partnered at the time of death (2000-2011). MEASURES: Hospice use at least 1 day in the last year of life as measured via Medicare claims data. Spousal factors (e.g., education and health status) measured via survey. RESULTS: In multivariate models controlling for patient factors and regional variation, spouses with lower educational attainment than their deceased spouse had decreased likelihood of hospice use (odds ratio [OR] = 0.58; 95% confidence interval [CI] = 0.40-0.82). Health of the spouse was not significantly associated with likelihood of decedent hospice use in adjusted models. IMPLICATIONS: Although the health of the surviving spouse was not associated with hospice use, their educational level was a predictor of hospice use. Spousal and family characteristics, including educational attainment, should be examined further in relation to disparities in hospice use. Efforts to increase access to high-quality end-of-life care for individuals with serious illness must also address the needs and concerns of caregivers and family. PMID- 26991834 TI - Concealing emotions: nurses' experiences with induced abortion care. AB - AIMS AND OBJECTIVES: To explore the experiences of nurses involved with induced abortion care in the delivery room in Taiwan. BACKGROUND: Induced abortion has emotional, ethical and legal facets. In Taiwan, several studies have addressed the ethical issues, abortion methods and women's experiences with abortion care. Although abortion rates have increased, there has been insufficient attention on the views and experiences of nurses working in the delivery room who are involved with induced abortion care. DESIGN: Qualitative, semistructured interviews. METHODS: This study used a purposive sampling method. In total, 22 nurses involved with induced abortion care were selected. Semistructured interviews with guidelines were conducted, and the content analysis method was used to analyse the data. RESULTS: Our study identified one main theme and five associated subthemes: concealing emotions, which included the inability to refuse, contradictory emotions, mental unease, respect for life and self-protection. CONCLUSION: This is the first specific qualitative study performed in Taiwan to explore nurses' experiences, and this study also sought to address the concealing of emotions by nurses when they perform induced abortion care, which causes moral distress and creates ethical dilemmas. The findings of this study showed that social-cultural beliefs profoundly influence nurses' values and that the rights of nurses are neglected. RELEVANCE TO CLINICAL PRACTICE: The profession should promote small-group and case-study discussions, the clarification of values and reflective thinking among nurses. Continued professional education that provides stress relief will allow nurses to develop self-healing and self-care behaviours, which will enable them to overcome the fear of death while strengthening pregnancy termination counselling, leading to better quality professional care. PMID- 26991835 TI - Vitamin D and gonadal function in men: a potential inverse U-shaped association? AB - Accumulating evidence from animal and human studies suggests that vitamin D, apart from its regulatory effects on musculoskeletal health, is involved in reproductive function in both genders. The basis of the interplay between vitamin D and reproduction lays on the presence of both vitamin D receptor (VDR) and 1alpha-hydroxylase (CYP27B1) enzyme in reproductive organs. In males, VDR are present in testis, epididymis, prostate, and seminal vesicles. In Sertoli cells, whose secretory activities are ion channel-dependent, vitamin D has been shown to stimulate calcium uptake through a nuclear receptor activity. Epidemiological studies support a positive association between serum 25-hydroxy-vitamin D [25(OH)D] concentrations and sperm motility in both fertile and infertile men In addition, large multi-center, cross-sectional studies from Europe and USA have shown positive, linear association between 25(OH)D and androgen concentrations. On the contrary, there are studies that support an inverse U-shaped association, that is, men with both low and high 25(OH)D concentrations demonstrate poorer gonadal function compared with those with intermediate concentrations. Given the rapid increase in over-the-counter use of vitamin D supplements by men that anticipate advantageous health outcomes, the aim of the present commentary is to provide an overview of the studies that present either U-shaped or linear association between 25(OH)D concentrations and male gonadal function. PMID- 26991837 TI - Estimating the extent and structure of trade in horticultural orchids via social media. AB - The wildlife trade is a lucrative industry involving thousands of animal and plant species. The increasing use of the internet for both legal and illegal wildlife trade is well documented, but there is evidence that trade may be emerging on new online technologies such as social media. Using the orchid trade as a case study, we conducted the first systematic survey of wildlife trade on an international social-media website. We focused on themed forums (groups), where people with similar interests can interact by uploading images or text (posts) that are visible to other group members. We used social-network analysis to examine the ties between 150 of these orchid-themed groups to determine the structure of the network. We found 4 communities of closely linked groups based around shared language. Most trade occurred in a community that consisted of English-speaking and Southeast Asian groups. In addition to the network analysis, we randomly sampled 30 groups from the whole network to assess the prevalence of trade in cultivated and wild plants. Of 55,805 posts recorded over 12 weeks, 8.9% contained plants for sale, and 22-46% of these posts pertained to wild-collected orchids. Although total numbers of posts about trade were relatively small, the large proportion of posts advertising wild orchids for sale supports calls for better monitoring of social media for trade in wild-collected plants. PMID- 26991836 TI - Targeting IkappaB kinase beta in Adipocyte Lineage Cells for Treatment of Obesity and Metabolic Dysfunctions. AB - IkappaB kinase beta (IKKbeta), a central coordinator of inflammation through activation of nuclear factor-kappaB, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKKbeta and found that IKKbeta ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKKbeta ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKKbeta signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKKbeta in 3T3 L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of adipose progenitor IKKbeta signaling in diet-induced obesity, we generated mice that selectively lack IKKbeta in the white adipose lineage and confirmed the essential role of IKKbeta in mediating adipocyte differentiation in vivo. Deficiency of IKKbeta decreased HF-elicited adipogenesis in addition to reducing inflammation and protected mice from diet-induced obesity and insulin resistance. Further, pharmacological inhibition of IKKbeta also blocked human adipose stem cell differentiation. Our findings establish IKKbeta as a pivotal regulator of adipogenesis and suggest that overnutrition-mediated IKKbeta activation serves as an initial signal that triggers adipose progenitor cell differentiation in response to HF feeding. Inhibition of IKKbeta with antisense therapy may represent as a novel therapeutic approach to combat obesity and metabolic dysfunctions. Stem Cells 2016;34:1883-1895. PMID- 26991839 TI - Improvement on binding of chondroitin sulfate derivatives to midkine by increasing hydrophobicity. AB - The interactions between chondroitin sulfate (CS) and a wide number of proteins modulate important biological processes. Here, the binding properties to midkine and pleiotrophin of sulfated, fully protected intermediates, typically obtained in the chemical synthesis of CS oligosaccharides, were tested for the first time. Using a fluorescence polarization competition experiment, we discovered that these synthetic precursors strongly bound these two closely related cytokines involved in cancer and inflammation. The relative binding affinities of these intermediates were significantly higher than those displayed by the corresponding fully deprotected oligosaccharides, indicating that the presence of hydrophobic protecting groups strongly enhanced the binding of CS-like derivatives to midkine. These compounds offer novel opportunities for the development of potent inhibitors/activators of CS-protein interactions with potential therapeutic applications. PMID- 26991838 TI - Maternal high-salt diet altered PKC/MLC20 pathway and increased ANG II receptor mediated vasoconstriction in adult male rat offspring. AB - SCOPE: High-salt diet (HSD) is associated with cardiovascular diseases. This study aims at ascertaining the influence of maternal HSD on offspring's angiotensin II (ANG II)-mediated vasoconstriction and the underlying mechanisms. METHODS AND RESULTS: In comparison to a normal-salt diet, HSD used in pregnancy in rats changed the ultrastructures of the coronary artery (CA) in 5-month-old male offspring, and increased ANG II-mediated CA contractility. Measurement of [Ca(2+) ]i in CA using fluorescent fura-2, a Ca(2+) indicator, showed that ANG II mediated increases in [Ca(2+) ]i were the same between HSD and normal-salt diet groups, but the ratio of diameter change/[Ca(2+) ]i induced by ANG II were significantly higher in HSD groups. Angiotensin II receptor type 1, not angiotensin II receptor type 2, caused ANG II-mediated vasoconstriction. Protein kinase C (PKC) inhibitor GF109203X attenuated the ANG II-mediated vasoconstriction, PKC agonist phorbol12,13-dibutyrate produced a greater contraction. There was an increase in PKCbeta mRNA and the corresponding protein abundance in the offspring, whereas other PKC subunits PKCalpha, PKCdelta, and PKCepsilon did not change. Moreover, 20 kDa myosin light chain phosphorylation levels were increased in HSD group. CONCLUSION: Maternal HSD affected the developmental programing for the offspring CA, with increased ANG II-mediated vasoconstrictions. The angiotensin II receptor type 1-PKC-20 kDa myosin light chain phosphorylation pathway was the possible mediated cellular mechanism. PMID- 26991840 TI - Variation in form of mandibular, light, round, preformed NiTi archwires. AB - OBJECTIVE: To evaluate the variation in form of nickel-titanium (NiTi) archwires by comparing them with the dental arch form of normal Japanese subjects before and after placing them in the first molar tubes. MATERIALS AND METHODS: The mandibular dental casts of 30 normal subjects were scanned, and the dental arch depths and widths from the canine to the first molar were measured. Standardized images of 34 types of 0.016-inch preformed NiTi archwires were also taken in a 37 degrees C environment, and the widths were measured and then classified by cluster analysis. Images of these archwires placed in a custom jig with brackets attached at the mean locations of the normal mandibular central incisors and first molar were additionally taken. The widths of the pooled and classified archwires were then compared with the normal dental arch widths before and after placement in the jig and among the groups (P < .05). RESULTS: The archwires were classified into three groups: small, medium, and large. The archwire widths in the small and medium groups were narrower than those at all examined tooth widths, except in the case of the premolars of the medium group. After placement in the jig, the pooled archwire widths were found to be significantly narrower and wider at the canine and second premolar, respectively, than at the dental arch, but not in the individual comparisons between groups. CONCLUSION: The variation observed in the mandibular NiTi archwire forms significantly decreased following fitting into the normal positions of the first molars. PMID- 26991841 TI - Relationship between dental crowding and mandibular incisor proclination during orthodontic treatment without extraction of permanent mandibular teeth. AB - OBJECTIVE: To examine changes in mandibular incisor proclination and protrusion resulting from alleviation of crowding. MATERIALS AND METHODS: Records of 96 patients from a private practice treated without extractions or interproximal enamel reduction in the mandibular arch were included. Pre- and post-treatment cephalograms and models were examined to determine changes in incisor proclination, protrusion and crowding. RESULTS: For every millimeter of crowding alleviation, increases in incisor proclination (DeltaIMPA) and protrusion (DeltaL1 to A-Pog) of 0.5 degrees and 0.2 mm, respectively, were found, on average. High variability was calculated for both linear variables (that can be reduced by incorporating other variables by multilinear regression). CONCLUSIONS: For every millimeter of crowding alleviated, 0.5 degrees of proclination and 0.2 mm of protrusion are expected. Our results indicate that proclination is mulifactorial and cannot be explained solely by the amount of crowding alleviated during orthodontic treatment. These results may be a useful guiding principle rather than a prognostic tool. PMID- 26991842 TI - Reaction Mechanism and Regioselectivity of the Bingel-Hirsch Addition of Dimethyl Bromomalonate to La@C2v -C82. AB - We quantum chemically explore the thermodynamics and kinetics of all 65 possible mechanistic pathways of the Bingel-Hirsch addition of dimethyl bromomalonate to the endohedral metallofullerene La@C2v -C82 that result from the combination of 24 nonequivalent carbon atoms and 35 different bonds present in La@C2v -C82 by using dispersion-corrected DFT calculations. Experimentally, this reaction leads to four singly bonded derivatives and one fulleroid adduct. Of these five products, only the singly bonded derivative on C23 could be experimentally identified unambiguously. Our calculations show that La@C2v -C82 is not particularly regioselective under Bingel-Hirsch conditions. From the obtained results, however, it is possible to make a tentative assignment of the products observed experimentally. We propose that the observed fulleroid adduct results from the attack at bond 19 and that the singly bonded derivatives correspond to the C2, C19, C21, and C23 initial attacks. However, other possibilities cannot be ruled out completely. PMID- 26991844 TI - Photo-protective effect of sargachromenol against UVB radiation-induced damage through modulating cellular antioxidant systems and apoptosis in human keratinocytes. AB - The aim of this study was to evaluate the photo-preventive effects of sargachromenol (SC) against ultraviolet B (UVB)-induced oxidative stress in human keratinocytes via assessing the antioxidant properties and underlying molecular mechanisms. SC exhibited a significant scavenging effect on UVB-induced intracellular reactive oxygen species (ROS). SC attenuated UVB-induced oxidative macromolecular damage, including the protein carbonyl content, DNA strand break, and 8-isoprostane level. Furthermore, SC decreased UVB-induced Bax, cleaved caspase-9, and cleaved caspase-3 protein levels, but increased that of Bcl-2, which are well-known key mediators of apoptosis. Moreover, SC increased superoxide dismutase, catalase, and heme oxygenase-1 protein expression. Pre treatment with SC upregulated the main transcription factor of antioxidant enzymes, erythroid 2-related factor 2 level, which was reduced by UVB irradiation. Extracellular signal-regulated kinase (ERK) and Jun N-terminal kinases (JNK) are involved in the regulation of many cellular events, including apoptosis. SC treatment reversed ERK and JNK activation induced by UVB. Collectively, these data indicate that SC can provide remarkable cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and suggest the potential of developing a medical agent for ROS-induced skin diseases. PMID- 26991843 TI - Valorisation of untreated cane molasses for enhanced phytase production by Bacillus subtilis K46b and its potential role in dephytinisation. AB - BACKGROUND: The high cost of phytase production is the most limiting factor in its application in animal feeds. The present study aimed to develop a low-cost medium for production of a novel phytase in submerged fermentation using inexpensive agro-industrial by-products. The applicability of phytase in dephytinisation of commonly used food/feed ingredients, i.e. soybean meal and wheat bran, was also investigated. RESULTS: Using a one-factor-at-a-time approach, soybean meal and cane molasses were identified as significant agro industrial by-products and these factors were subsequently optimised using response surface methodology (RSM). A central composite design was employed to further enhance phytase yield. Under optimum conditions of soybean meal 22.3 g L 1 , cane molasses 100 g L-1 and 39 h fermentation, phytase production increased to 56.562 U mL-1 , indicating more than 28-fold enhancement. The enzyme efficiently dephytinised wheat bran and soybean meal after 24 h incubation at 56.5 degrees C and increased inorganic phosphate content by 240% and 155%, respectively. CONCLUSION: Soybean meal and cane molasses were successfully used for enhancement of phytase production as economical carbon, nitrogen and phytic acid sources using RSM. The phytase showed a good capability to dephytinise wheat bran and soybean meal, demonstrating that the enzyme can be considered as a potential candidate for industrial food and feed applications. (c) 2016 Society of Chemical Industry. PMID- 26991846 TI - The toxic effects on the stress and immune responses in juvenile rockfish, Sebastes schlegelii exposed to hexavalent chromium. AB - Juvenile Sebastes schlegelii (mean length 13.7+/-1.7cm, and mean weight 55.6+/ 4.8g) were exposed for 4 weeks with the different levels of dietary chromium (Cr(6+)) concentration (0, 30, 60, 120 and 200mg/L). The plasma cortisol and heat shock protein 70 was evaluated as stress indicators. Plasma cortisol was significantly increased in response to the dietary chromium exposure over 120mg/kg at 2 and 4 weeks. Heat shock protein 70 was also notably increased over 120mg/kg at 2 weeks and over 60mg/kg at 4 weeks. In the immune response, immunoglobulin M was considerably increased in the concentration of 240mg/kg at 2 weeks and over 120mg/kg at 4 weeks. Lysozyme activity was considerably induced by the dietary hexavalent chromium exposure. A significant increase in plasma lysozyme activity was observed at 240mg/kg after 2 weeks and over 60mg/kg after 4 weeks, kidney lysozyme was also increased over 120mg/kg at 2 and 4 weeks. The results demonstrate that dietary Cr exposure can induce a significant stress and immune stimulation. PMID- 26991845 TI - Ribosomal protein L7 as a suitable reference gene for quantifying gene expression in gastropod Bellamya aeruginosa. AB - Expression levels of eight candidate reference genes were quantified in tissues of gastropod Bellamya aeruginosa exposed for 10 d to various stressors, including fasting, 17beta-estradiol, 17alpha-methyltestosterone, and Cd(2+). The results showed that 18s rRNA was the most highly expressed of the candidate reference genes, while H2A was the least expressed. There were no significant changes (p>0.05) in the expression of the eight genes in tissues among the different treatments. Using RefFinder to evaluate the expression stabilities of the eight candidate reference genes, ribosomal protein was shown to be the most stable reference gene, and no effects were observed among the different stressor treatments. These results indicate that RPL 7 is the most suitable reference gene for quantifying gene expression in B. aeruginosa under environmental stress, which was verified in B. aeruginosa exposed to high doses of E2 for 24 and 72h. PMID- 26991847 TI - Molecular mechanism of brain impairment caused by drinking-acquired fluorosis and selenium intervention. AB - This study investigated the molecular mechanism of brain impairment induced by drinking fluoridated water and selenium intervention. Results showed that the learning and memory of rats in NaF group significantly decreased. Moreover, the number of apoptotic cells, the expression levels of Cytc mRNA and protein, and the expression levels of Caspase-9 and Caspase-3 mRNA significantly increased; by contrast, Caspase-9 and Caspase-3 protein levels significantly decreased. Compared with the NaF group, the mRNA levels of Cytc and Caspase-9, as well as the protein levels of Cytc in NaF+Se group, significantly decreased. Conversely, the protein levels of Caspase-3 and Caspase-9, as well as the mRNA levels of Caspase-3, significantly increased. Thus, the mitochondrial CytC-Caspase-9 Caspase-3 apoptosis pathway in the hippocampus was one of the mechanisms leading to fluorosis-induced brain damage. Furthermore, the Cytc signaling molecules were possibly the key target molecules in fluorosis-induced apoptosis, and selenium could alleviate fluorosis-induced brain injury. PMID- 26991848 TI - Desmethylanhydroicaritin isolated from Sophora flavescens, shows antitumor activities in U87MG cells via inhibiting the proliferation, migration and invasion. AB - This study is the first report of the antitumor activities of desmethylanhydroicaritin (DMAI) isolated from Sophora flavescens on U87MG cells. Human glioblastoma is one of the most aggressive malignant type of brain tumors and highly diffuses to around normal brain tissues. DMAI showed anti proliferation effects on U87MG cells at the concentration of 30MUM, however did not affect to HEK-293 cells. DMAI induced anti-proliferation effects via ERK/MAPK, PI3K/Akt/mTOR signal pathway and G2/M phase cell cycle arrest. DMAI led to morphological change and inhibition of filapodia formation through regulation of Rac 1 and Cdc 42. In addition, migration and invasion of U87MG cells were inhibited by DMAI via down-regulation of matrix metalloproteinase (MMP) -2 and MMP -9 expressions and activities. Our results suggest that DMAI has a potential as a therapeutic agent against glioblastoma cells. PMID- 26991849 TI - Plasma phthalate and bisphenol a levels and oxidant-antioxidant status in autistic children. AB - Phthalates and bisphenol A (BPA) are endocrine disruting chemicals (EDCs) that are suggested to exert neurotoxic effects. This study aimed to determine plasma phthalates and BPA levels along with oxidant/antioxidant status in autistic children [n=51; including 12 children were diagnosed with "Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS)]. Plasma levels of BPA, di (2-ethylhexyl)-phthalate (DEHP) and its main metabolite mono (2-ethylhexyl) phthalate (MEHP); thiobarbituric acid reactive substance (TBARS) and carbonyl groups; erythrocyte glutathione peroxidase (GPx1), thioredoxin reductase (TrxR), catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR) activities and glutathione (GSH) and selenium levels were measured. Plasma BPA levels of children with PDD-NOS were significantly higher than both classic autistic children and controls (n=50). Carbonyl, selenium concentrations and GPx1, SOD and GR activities were higher (p<0.05); CAT activity was markedly lower in study group. BPA exposure might be associated with PDD-NOS. Intracellular imbalance between oxidant and antioxidant status might facilitate its neurotoxicity. PMID- 26991850 TI - Parent and adolescent reports in assessing adolescent sleep problems: results from a large population study. AB - AIM: To compare parent and adolescent reports in exploring adolescent sleep problems and to identify the factors associated with adolescent sleep problem disclosures. METHODS: Parent (n = 5185) and adolescent reports (n = 5171, age=13.9 +/- 0.3 years), from a birth cohort were used to explore adolescent sleep problems. Kappa coefficients were used to assess the agreement, whereas, conditional agreement and disagreement ratios were used to identify the optimal informant. Logistic regression analysis was used to determine the factors affecting adolescent sleep problem disclosure. RESULTS: Parental reports identified only about one-third of the sleep problems reported by adolescents. Whereas adolescent reports identified up to two-thirds of the sleep problems reported by parents. Combined reports of parents and adolescent did not show any considerable difference from the adolescent report. Adolescent and parent health, maternal depression, and family communication were significantly associated with adolescents sleep problem disclosures. CONCLUSION: Adolescent reports could be used as the preferred source to explore adolescent sleep problems. Parental reports should be used when parents as observers are more reliable reporters, or where adolescents are cognitively unable to report sleep problems. Additionally, the impact of poor health, maternal depression and family communication on sleep problems disclosure should be considered for adolescent sleep problem diagnosis. PMID- 26991852 TI - Stimulatory Effects of Coumestrol on Embryonic and Fetal Development Through AKT and ERK1/2 MAPK Signal Transduction. AB - Successful establishment of pregnancy is required for fetal-maternal interactions regulating implantation, embryonic development and placentation. A uterine environment with insufficient growth factors and nutrients increases the incidence of intrauterine growth restriction (IUGR) leading to an impaired uterine environment. In the present study, we demonstrated the effects of the phytoestrogen coumestrol on conceptus development in the pig that is regarded as an excellent biomedical animal model for research on IUGR. Results of this study indicated that coumestrol induced migration of porcine trophectoderm (pTr) cells in a concentration-dependent manner. In response to coumestrol, the phosphorylation of AKT, P70S6K, S6, ERK1/2 MAPK, and P90RSK proteins were activated in pTr cells and ERK1/2 MAPK and P90RSK phosphorylation was prolonged for a longer period than for the other proteins. To identify the signal transduction pathway induced by coumestrol, pharmacological inhibitors U0126 (an ERK1/2 inhibitor) and LY294002 (a PI3K inhibitor) were used to pretreat pTr cells. The results showed that coumestrol-induced phosphorylation of ERK1/2 MAPK and P90RSK was blocked by U0126. In addition, the increased phosphorylation in response to coumestrol was completely inhibited following pre-treatment incubation of pTr cells in the presence of LY294002 and U0126. Furthermore, these two inhibitors suppressed the ability of coumestrol to induce migration of pTr cells. Collectively, these findings suggest that coumestrol affects embryonic development through activation of the PI3K/AKT and ERK1/2 MAPK cell signal transduction pathways and improvement in the uterine environment through coumestrol supplementation may provide beneficial effects of enhancing embryonic and fetal survival and development. J. Cell. Physiol. 231: 2733-2740, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991851 TI - Co-introduction of a steroid with docetaxel chemotherapy for metastatic castration-resistant prostate cancer affects PSA flare. AB - OBJECTIVE: To investigate the potential relationship of steroid usage with prostate-specific antigen (PSA) flare as well as the prognostic impact of PSA flare, which is known to occur in 10-20% of patients with metastatic castration resistant prostate cancer during docetaxel chemotherapy. PATIENTS AND METHODS: This study included 71 patients with metastatic castration-resistant prostate cancer treated by docetaxel chemotherapy with co-introduction of a steroid. PSA flare was defined as a transient PSA increase followed by a PSA decrease. RESULTS: PSA flare was recognized in 7.0-23.9% of patients according to the definition used. Intriguingly, men with steroid intake before the initiation of docetaxel chemotherapy experienced significantly fewer PSA flares. The progression-free survival rate in men with PSA flare was equivalent to that of PSA responders, but significantly better than men with PSA failure. CONCLUSIONS: Our results suggest that de novo steroid co-introduction with docetaxel chemotherapy induces the PSA flare phenomenon. This novel finding may account for the mechanism of PSA flare as well as being valuable for distinguishing PSA elevation attributable to PSA flare from that attributable to PSA failure. PMID- 26991854 TI - Recombination hotspots: Models and tools for detection. AB - Recombination hotspots are the regions within the genome where the rate, and the frequency of recombination are optimum with a size varying from 1 to 2kb. The recombination event is mediated by the double-stranded break formation, guided by the combined enzymatic action of DNA topoisomerase and Spo 11 endonuclease. These regions are distributed non-uniformly throughout the human genome and cause distortions in the genetic map. Numerous lines of evidence suggest that the number of hotspots known in humans has increased manifold in recent years. A few facts about the hotspot evolutions were also put forward, indicating the differences in the hotspot position between chimpanzees and humans. In mice, recombination hot spots were found to be clustered within the major histocompatibility complex (MHC) region. Several models, that help explain meiotic recombination has been proposed. Moreover, scientists also developed some computational tools to locate the hotspot position and estimate their recombination rate in humans is of great interest to population and medical geneticists. Here we reviewed the molecular mechanisms, models and in silico prediction techniques of hot spot residues. PMID- 26991853 TI - DNA damage response (DDR) pathway engagement in cisplatin radiosensitization of non-small cell lung cancer. AB - Non-small cell lung cancers (NSCLC) are commonly treated with a platinum-based chemotherapy such as cisplatin (CDDP) in combination with ionizing radiation (IR). Although clinical trials have demonstrated that the combination of CDDP and IR appear to be synergistic in terms of therapeutic efficacy, the mechanism of synergism remains largely uncharacterized. We investigated the role of the DNA damage response (DDR) in CDDP radiosensitization using two NSCLC cell lines. Using clonogenic survival assays, we determined that the cooperative cytotoxicity of CDDP and IR treatment is sequence dependent, requiring administration of CDDP prior to IR (CDDP-IR). We identified and interrogated the unique time and agent dependent activation of the DDR in NSCLC cells treated with cisplatin-IR combination therapy. Compared to treatment with CDDP or IR alone, CDDP-IR combination treatment led to persistence of gammaH2Ax foci, a marker of DNA double-strand breaks (DSB), for up to 24h after treatment. Interestingly, pharmacologic inhibition of DDR sensor kinases revealed the persistence of gamma H2Ax foci in CDDP-IR treated cells is independent of kinase activation. Taken together, our data suggest that delayed repair of DSBs in NSCLC cells treated with CDDP-IR contributes to CDDP radiosensitization and that alterations of the DDR pathways by inhibition of specific DDR kinases can augment CDDP-IR cytotoxicity by a complementary mechanism. PMID- 26991855 TI - Cerebrospinal fluid biomarkers for Parkinson's disease - a systematic review. AB - Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments. Developments in analytical chemistry allow the detection of large numbers of molecules in plasma or cerebrospinal fluid, associated with the pathophysiology or pathogenesis of PD. This systematic review includes cerebrospinal fluid biomarker studies focusing on different disease pathways: oxidative stress, neuroinflammation, lysosomal dysfunction and proteins involved in PD and other neurodegenerative disorders, focusing on four clinical domains: their ability to (1) distinguish PD from healthy subjects and other neurodegenerative disorders as well as their relation to (2) disease duration after initial diagnosis, (3) severity of disease (motor symptoms) and (4) cognitive dysfunction. Oligomeric alpha-synuclein might be helpful in the separation of PD from controls. Through metabolomics, changes in purine and tryptophan metabolism have been discovered in patients with PD. Neurofilament light chain (NfL) has a significant role in distinguishing PD from other neurodegenerative diseases. Several oxidative stress markers are related to disease severity, with the antioxidant urate also having a prognostic value in terms of disease severity. Increased levels of amyloid and tau-proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD. In the future, larger longitudinal studies, corroborating previous research on viable biomarker candidates or using metabolomics identifying a vast amount of potential biomarkers, could be a good approach. PMID- 26991856 TI - Trends in computed tomography utilisation in the emergency department: A 5 year experience in an urban medical centre in northern Taiwan. AB - BACKGROUND: Steady increase in computed tomography (CT) utilisation in the ED was observed in countries such as the USA, Canada, China and Korea; however, limited empirical data are available regarding Taiwan. OBJECTIVE: The objective of the present study is to quantify and compare trends in CT utilisation in the ED over a 5 year period in a medical centre in Taiwan. METHODS: Electronic chart review was performed in a medical centre with an annual ED census of 80 000 patients. Subjects >20 years of age who underwent CT scans during ED visits from 1 January 2005 to 31 December 2009 were identified. RESULTS: Among the 333 673 adult ED visits, 43 635 received CT scans, with a utilisation rate of 131 per 1000. Within the 5 year span, patient volume increased by 7.7%, whereas CT utilisation increased by 42.7%. The rates of increase in patient volume and CT utilisation were 5.0% and 32.4% in non-trauma; 19.7% and 97.8% in trauma. CT scans were mostly performed on the head (47%), abdomen (36%), followed by chest (10%) and miscellaneous (7%). An increase of 168% in spinal CTs for trauma patients was observed. An increase in CT utilisation was found in all age groups with a proportionate increase with increasing age in both trauma and non-trauma. CONCLUSION: ED CT utilisation has increased at a rate far exceeding the growth in ED patient volume. This may be attributed to the improved utility of CT in diagnosing serious pathology, more diagnostic indications for CT, ready availability and the necessity for diagnostic certainty in the ED. PMID- 26991857 TI - Impact of the functional CD5 polymorphism A471V on the response of chronic lymphocytic leukaemia to conventional chemotherapy regimens. PMID- 26991858 TI - New classification of donation after circulatory death donors definitions and terminology. AB - In the face of a crisis in organ donation, the transplant community are increasingly utilizing donation after circulatory death (DCD) donors. Over the last 10 years, with the increasing usage of DCD donors, we have seen the introduction in a number of new terms and definitions. We report the results of the 6th International Conference in Organ Donation held in Paris in 2013 and report a consensus agreement of an established expert European Working Group on the definitions and terminology regarding DCD donation, including refinement of the Maastricht definitions. This document forms part of a special series where recommendations are presented for uncontrolled and controlled DCD donation and organ specific guidelines for kidney, pancreas, liver and lung transplantation. An expert panel formed a consensus on definitions and terms aiming to establish consistent usage of terms in DCD donation. PMID- 26991859 TI - The assessment of anticoagulant activity to predict bleeding outcome in atrial fibrillation patients receiving dabigatran etexilate. AB - Special circumstances may require the measurement of the anticoagulant effect of dabigatran etexilate. No data currently link any given coagulation test to bleeding outcomes in patients receiving dabigatran etexilate for atrial fibrillation. Nonvalvular atrial fibrillation patients receiving dabigatran etexilate of 110 mg (DE110) or 150 mg (DE150) were consecutively enrolled. The hemoclot thrombin inhibitor (HTI) assay, prothrombin time, and activated partial thromboplastin time (APTT) measurements were correlated with bleeding events during a prospective follow-up. There were 17 bleeding events (8.2%) in 208 patients (74.7 +/- 10.3 years old, 67.9% male, median follow-up: 364 days), whereas 15 patients with bleeding events used DE110. Compared with DE110, the patients receiving DE150 were younger and more often male and had lower HAS-BLED and CHA2DS2VASc scores and better renal function. Patients' HTI levels were very variable (DE110, 10-90th percentile: 20.5-223.9 ng/ml). A receiver-operator characteristic curve gave a median cutoff HTI level of 117.7 ng/ml to predict bleeding events (C-statistics: 0.65; P = 0.036), but no cutoff could be determined for prothrombin time or APTT. Based on the Kaplan-Meier analysis, a dabigatran etexilate level greater than 117.7 ng/ml was associated with a higher bleeding rate (15.4% vs. 4.9%, P = 0.01). After multivariate Cox regression analysis, HTI levels, history of stroke, and male sex were independent risk factors for bleeding events. Dabigatran etexilate-HTI levels were independently associated with bleeding in patients receiving routine clinical care. Blood sampling at multiple time points might be needed to increase reliability because of high variation of dabigatran etexilate-HTI levels. PMID- 26991860 TI - A method to measure thrombin activity in a mixture of fibrinogen and thrombin powders. AB - Thrombin and fibrinogen powders are the active components of advanced surgical hemostasis products including the EVARREST Fibrin Sealant Patch. Measuring the enzymatic activity of thrombin in the presence of fibrinogen is challenging, as hydration of the powders in a neutral aqueous environment will cause the enzyme to rapidly react with the fibrinogen to form a fibrin clot, which in turn binds and entraps the enzyme thus preventing subsequent measurement of thrombin activity. A novel approach has been developed to overcome this challenge. After isolation of the mixture of powders, an alkaline carbonate solution is used to solubilize the proteins, while reversibly inhibiting the activity of thrombin and preventing clot formation. Once the powders have been fully solubilized, thrombin activity can be restored by neutralization in a buffered fibrinogen solution resulting in fibrin clot formulation. The rate of clot formation can be quantified in a coagulometer to determine the thrombin activity of the original powder. Samples coated with powders containing fibrinogen and varying amounts of thrombin were tested using the method described herein. The results demonstrated that the method could consistently measure the activity of (alpha) thrombin in the presence of fibrinogen over a broad range of thrombin activity levels. The test was successfully validated according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines and thus is suitable for use as part of a commercial manufacturing process. A method has been developed that enables thrombin activity to be measured in a mixture of fibrinogen and thrombin powders. PMID- 26991861 TI - An Immucillin-Based Transition-State-Analogous Inhibitor of tRNA-Guanine Transglycosylase (TGT). AB - Shigellosis is one of the most severe diarrheal diseases worldwide without any efficient treatment so far. The enzyme tRNA-guanine transglycosylase (TGT) has been identified as a promising target for small-molecule drug design. Herein, we report a transition-state analogue, a small, immucillin-derived inhibitor, as a new lead structure with a novel mode of action. The complex inhibitor synthesis was accomplished in 18 steps with an overall yield of 3 %. A co-crystal structure of the inhibitor bound to Z. mobilis TGT confirmed the predicted conformation of the immucillin derivative in the enzyme active site. PMID- 26991862 TI - Changes in the Functional Potential of the Gut Microbiome Following Probiotic Supplementation during Helicobacter Pylori Treatment. AB - BACKGROUND: Probiotic supplementation is utilized to alleviate the side effects associated with antibiotic therapy for Helicobacter pylori infection. Several studies have described the effects of administration of probiotics on the gut microbiota during antibiotic therapy. However, most of these studies have focused on specific bacteria, thereby providing limited information on the functional roles of the altered microbiota. Therefore, we examined the impact of probiotic supplementation on the structure and functional dynamics of the gut microbiota during H. pylori eradication, using whole-metagenomic sequence analysis. METHODS: Subjects were divided into two groups: the antibiotics group, which received only antibiotics, and the probiotics group, which received antibiotics with probiotic supplementation. The structural and functional profiles of gut microbiota was analyzed using metagenomic DNA extracted from the feces during treatment by Illumina MiSeq system. RESULTS: The overall alterations in microbiota, as revealed by whole metagenome sequencing, were similar with results from our previous 16S rRNA gene-based analysis. The proportional shift in functional gene families was greater in the antibiotics group than in the probiotics group. In particular, the proportion of genes related to selenocompound metabolism was reduced in the probiotics group, whereas genes associated with the metabolism of nucleotide sugars were increased. CONCLUSION: The functional alterations of gut microbiota may link to the reduction in intestinal irritation and maintenance of bacterial diversity observed following probiotic supplementation with antibiotic therapy. The potential beneficial roles of altered gut microbiota following probiotic supplementation are expected a reduction in side effects such as intestinal irritation and antibiotics resistance. PMID- 26991863 TI - Morphology-Specific Inhibition of beta-Amyloid Aggregates by 17beta Hydroxysteroid Dehydrogenase Type 10. AB - A major hallmark of Alzheimer's disease (AD) is the formation of toxic aggregates of the beta-amyloid peptide (Abeta). Given that Abeta peptides are known to localise within mitochondria and interact with 17beta-HSD10, a mitochondrial protein expressed at high levels in AD brains, we investigated the inhibitory potential of 17beta-HSD10 against Abeta aggregation under a range of physiological conditions. Fluorescence self-quenching (FSQ) of Abeta(1-42) labelled with HiLyte Fluor 555 was used to evaluate the inhibitory effect under conditions established to grow distinct Abeta morphologies. 17beta-HSD10 preferentially inhibits the formation of globular and fibrillar-like structures but has no effect on the growth of amorphous plaque-like aggregates at endosomal pH 6. This work provides insights into the dependence of the Abeta-17beta-HSD10 interaction with the morphology of Abeta aggregates and how this impacts enzymatic function. PMID- 26991864 TI - Delineation of a recognizable phenotype for the recurrent LCR22-C to D/E atypical 22q11.2 deletion. AB - The 22q11.2 deletion syndrome is typically caused by haploinsufficiency of a 3 Mb region that extends from LCR22-A until LCR22-D, while the recurrent recombination between any of the LCR22-D to H causes the 22q11.2 distal deletion syndrome. Here, we describe three patients with a de novo atypical ~1.4 Mb 22q11.2 deletion that involves LCR22-C to a region beyond D (LCR22-C to D/E), encompassing the distal portion of the typical deleted region and the proximal portion of the distal deletion. We also review six previous published patients with the same rearrangement and compare their features with those found in patients with overlapping deletions. Patients with LCR22-C to D/E deletion present a recognizable phenotype characterized by facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay. Genotype-phenotype analysis of the patients indicates that CRKL and MAPK1 genes play an important role as causative factors for the main clinical features of the syndrome. In particular, CRKL gene seems to be involved in the occurrence of conotruncal cardiac anomalies, mainly tetralogy of Fallot. (c) 2016 Wiley Periodicals, Inc. PMID- 26991865 TI - Preconcentration of valsartan by dispersive liquid-liquid microextraction based on solidification of floating organic drop and its determination in urine sample: Central composite design. AB - In this work, a fast, easy, and efficient dispersive liquid-liquid microextraction method based on solidification of floating organic drop followed by high-performance liquid chromatography with UV detection was developed for the separation/preconcentration and determination of the drug valsartan. Experimental design was applied for the optimization of the effective variables (such as volume of extracting and dispersing solvents, ionic strength, and pH) on the extraction efficiency of valsartan from urine samples. The optimized values were 250.0 MUL ethanol, 65.0 MUL 1-dodecanol, 4.0% w/v NaCl, pH 3.8, 1.0 min extraction time, and 4.0 min centrifugation at 4000 rpm min(-1) . The linear response (r(2) = 0.997) was obtained in the range of 0.013-10.0 MUg mL(-1) with a limit of detection of 4.0 ng mL(-1) and relative standard deviations of less than 5.0 % (n = 6). PMID- 26991866 TI - Psoriasis and adverse pregnancy outcomes: a systematic review of observational studies. AB - Psoriasis is a chronic inflammatory disorder with significant physical and psychological sequelae. The majority of individuals experience disease onset in early adult life - for women this often occurs during their reproductive years. While some autoimmune diseases have been shown to affect pregnancy outcomes adversely, such a relationship has not been well studied in psoriasis. We searched PubMed, Embase and the Cochrane database for published articles examining psoriasis and adverse pregnancy outcomes, and included observational studies and clinical trials evaluating direct measures of maternal and fetal morbidity and mortality. Four of the nine included articles reported a statistically significant increase in the risk of at least one outcome, including spontaneous abortion, caesarean delivery, low birth weight, macrosomia, large-for gestational age, and a composite outcome consisting of both prematurity and low birth weight. However, these associations were not always consistent across studies. Overall, there was no clear evidence of increased adverse outcomes in pregnant women with psoriasis. PMID- 26991867 TI - Facile Assembly of Benzo[b]naphtho[2,3-d]azocin-6(5 H)-ones by a Palladium Catalyzed Double Carbometalation. AB - The palladium-catalyzed reaction of 2-alkynylanilines with 2-(2 bromobenzylidene)cyclobutanone as an efficient route to 7,8 dihydrobenzo[b]naphtho[2,3-d]azocin-6(5 H)-ones was developed. The fused eight membered ring was constructed conveniently. During the reaction process, double carbometalation was involved, which resulted in excellent selectivity with the formation of three new bonds. This transformation is highly efficient and leads to fused polycycles in good to excellent yields with good functional group tolerance. PMID- 26991868 TI - Risks and Threats of Social Media Websites: Twitter and the Proana Movement. AB - In recent years, there was a spread of "proanorexia" Web sites. The aim of our study is to investigate the presence, popularity, and content of the "proana" accounts on Twitter. On January 2015, we used "Twitter Search" to retrieve the "proana" accounts. For each account, we analyzed the number of followers, tweets, and the biographical information of the users. We followed these accounts for 4 weeks, assessing the variations in followers and tweets. We also investigated the most used hashtags and the main contents of these profiles. We retrieved 341 accounts. These accounts were popular (mean followers: 2360.9, range: 5-32,700) and active (mean tweets: 4351.2, range: 5-85,700). The users were mostly girls (97.9 percent), in general teenagers (mean age: 17.9 years, range: 12-28). Only around six percent of the accounts presented a warning text about the dangerous content. Each week, we found a mean increase in both followers and tweets. The five most used hashtags resulted in descending order as follows: "thinspo," "thinspiration," "Thin15," "EDprobs," and "proana." The most commonly used contents were in the following order: autobiographic, "thinspiration" photos (inspirational photos of extremely thin girls), "thinspiration" quotes (motivational mottos), "ana tips" (advices for weight loss), and "fasting competition." We underlined a concerning high number and popularity of Twitter proanorexia groups. These accounts contain dangerous information, especially considering the young age of the users. Given the lack of warnings in almost all the accounts, a first step to control this phenomenon could be the increase of such written alerts. PMID- 26991870 TI - An e13a3 BCR-ABL1 fusion transcript in variant t(9;22;17)(q34;q11;q21)-positive adult acute lymphoblastic leukemia. PMID- 26991869 TI - Effect of supine body position on central corneal thickness. AB - BACKGROUND: To evaluate the effect of supine body position on central corneal thickness (CCT) in open-angle glaucoma patients and in healthy subjects. DESIGN: A cross-sectional study at a university eye clinic. PARTICIPANTS: Twenty-three subjects were recruited in each group, for a total of 46 patients. METHODS: CCT was measured using an ultrasound pachymeter in each subject. Three consecutive measurements in each eye were first taken in the sitting position, and repeated after 10 min and 30 min in a supine position. Results were analyzed using mixed model repeated measures, which adjusted for age, gender and laterality of eyes. MAIN OUTCOME MEASURES: CCT RESULTS: In healthy subjects, CCT decreased with supine positioning at 10 min (mean = -5.2 um, P = 0.0043) and at 30 min (mean = 6.5 um, P < 0.0001). In the glaucoma group, CCT decreased with supine positioning at 10 min (mean = -6.7 um, P = 0.0043) and at 30 min (mean = -10.2 um, P < 0.0001). There was no statistically significant difference between the CCT at 10 min supine and at 30 min supine in the healthy subjects (P = 0.37) and glaucoma patients (P = 0.14). CCT was shown to decrease linearly over time (P < 0.0001), and the slopes were not statistically different between groups (P = 0.40). CONCLUSIONS: CCT is a dynamic measurement that can be influenced by body position. It decreases linearly in the first 30 min of supine positioning at a similar rate in both open angle glaucoma patients and in healthy subjects. PMID- 26991871 TI - Emerging functions of the Quaking RNA-binding proteins and link to human diseases. AB - RNA-binding proteins (RBPs) are essential players in RNA metabolism including key cellular processes from pre-mRNA splicing to mRNA translation. The K homology type QUAKING RBP is emerging as a vital factor for oligodendrocytes, monocytes/macrophages, endothelial cell, and myocyte function. Interestingly, the qkI gene has now been identified as the culprit gene for a patient with intellectual disabilities and is translocated in a pediatric ganglioglioma as a fusion protein with MYB. In this review, we will focus on the emerging discoveries of the QKI proteins as well as highlight the recent advances in understanding the role of QKI in human disease pathology including myelin disorders, schizophrenia and cancer. WIREs RNA 2016, 7:399-412. doi: 10.1002/wrna.1344 For further resources related to this article, please visit the WIREs website. PMID- 26991872 TI - Hd1,a CONSTANS ortholog in rice, functions as an Ehd1 repressor through interaction with monocot-specific CCT-domain protein Ghd7. AB - Flowering time is an important agronomic trait that affects crop yields. In cereals, several CCT-domain proteins unique to monocots, such as Grain number, plant height, and heading date 7 (Ghd7) gene, have been identified as key floral repressors, although the corresponding molecular mechanisms have been unknown until now. In rice, a short-day plant, Heading date 1 (Hd1) gene, a rice ortholog of Arabidopsis floral activator CONSTANS (CO), represses flowering under non inductive long-day (LD) conditions and induces it under inductive short-day (SD) conditions. Here, we report biological interactions between Ghd7 and Hd1, which together repress Early heading date 1 (Ehd1), a key floral inducer under non inductive LD conditions. In addition to this genetic interaction between them, Co IP experiments further demonstrated that a Ghd7-Hd1 protein formed a complex in vivo and ChIP and luciferase reporter analyses suggested that this complex specifically binds to a cis-regulatory region in Ehd1 and represses its expression. These findings imply that Hd1, an evolutionally conserved transcriptional activator, can function as a strong transcriptional repressor within a monocot-specific flowering-time pathway through with Ghd7. PMID- 26991873 TI - New anticoagulants, a new book and old gags. PMID- 26991874 TI - Comparison of Carina active middle-ear implant with conventional hearing aids for mixed hearing loss. AB - OBJECTIVE: To compare the auditory outcomes of Carina middle-ear implants with those of conventional hearing aids in patients with moderate-to-severe mixed hearing loss. METHODS: The study comprised nine patients (six males, three females) who underwent middle-ear implantation with Carina fully implantable active middle-ear implants to treat bilateral moderate-to-severe mixed hearing loss. The patients initially used conventional hearing aids and subsequently received the Carina implants. The hearing thresholds with implants and hearing aids were compared. RESULTS: There were no significant differences between: the pre-operative and post-operative air and bone conduction thresholds (p > 0.05), the thresholds with hearing aids and Carina implants (p > 0.05), or the pre operative (mean, 72.8 +/- 19 per cent) and post-operative (mean, 69.9 +/- 24 per cent) speech discrimination scores (p > 0.05). One of the patients suffered total sensorineural hearing loss three months following implantation despite an initial 38 dB functional gain. All except one patient showed clinical improvements after implantation according to quality of life questionnaire (Glasgow Benefit Inventory) scores. CONCLUSION: Acceptance of Carina implants is better than with conventional hearing aids in patients with mixed hearing loss, although both yield similar hearing amplification. Cosmetic reasons appear to be critical for patient acceptance. PMID- 26991875 TI - Impact of unilateral carbon dioxide laser posterior transverse cordotomy on vocal and aerodynamic parameters in bilateral vocal fold paralysis. AB - OBJECTIVES: Carbon dioxide laser posterior transverse cordotomy is a common option for bilateral vocal fold paralysis. This study prospectively evaluated aerodynamic and acoustic effects of unilateral carbon dioxide laser posterior transverse cordotomy in bilateral vocal fold paralysis patients. METHODS: The study comprised 11 bilateral vocal fold paralysis patients (9 females, 2 males), with a mean age of 46.6 +/- 14.1 years. All patients were treated by laser posterior transverse cordotomy. Pre-operative and two-month post-operative assessments were conducted, including: dyspnoea scales, maximum phonation time measurement, spirometry and bicycle ergometry. RESULTS: All subjective and objective aerodynamic parameters showed statistically significant improvements between the pre- and post-operative period. Objective spirometric and ergometric parameters showed a significant increase post-operatively. The changes in objective voice parameters (fundamental frequency (f0), jitter, shimmer, soft phonation index and noise-to-harmonic ratio) were statistically non-significant; however, there was a significant improvement in subjective voice parameters post operatively, as assessed by the voice handicap index and grade-roughness breathiness-asthenia-strain scale (p = 0.026 and p = 0.018 respectively). CONCLUSION: Unilateral carbon dioxide laser posterior transverse cordotomy is an effective procedure that results in improved dyspnoea and aerodynamic performance with some worsening of voice parameters. PMID- 26991876 TI - A murine model of subglottic granulation. AB - OBJECTIVE: This study aimed to develop a functional model of subglottic stenosis by inducing direct airway irritation in transplanted mouse laryngotracheal complexes. METHODS: Laryngotracheal complexes from C57BL/6 mice were harvested and divided into three groups: uninjured, mechanically injured and chemically injured. Donor laryngotracheal complexes from each group were placed in dorsal subcutaneous pockets of recipient mice. Each week, the transplanted laryngotracheal complexes were harvested, and tissues were fixed, sectioned, and stained with haematoxylin and eosin. Representative slides were reviewed by a blinded pathologist, to determine the formation of granulation tissue, and graded as to the degree of granulation formation. RESULTS: Direct airway irritation induced granulation tissue formation under the disrupted epithelium of airway mucosa; this was seen as early as two weeks after chemical injury. CONCLUSION: Results indicate that granulation tissue formation in a murine model may be an efficient tool for investigating the development and treatment of subglottic stenosis. PMID- 26991877 TI - Active middle-ear implant fixation in an unusual place: clinical and audiological outcomes. AB - OBJECTIVE: The Vibrant Soundbridge is an active middle-ear implant for hearing rehabilitation that is usually placed in the long process of the incus or round window. This study reports on the unusual implant attachment to the short process of the incus in a patient with ear malformation, and describes their audiological and clinical outcomes. METHODS: Case report and literature review. RESULTS: Audiological evaluation with the Vibrant Soundbridge implant showed a pure tone average of 31 dB. The speech test, at 65 dB HL, revealed correct recognition of 92 per cent of disyllabic words. The Glasgow Hearing Aid Benefit Profile showed high levels of satisfaction, hearing aid use and benefit. CONCLUSION: Fixation of the Vibrant Soundbridge implant on the short process of the incus is a feasible option, with good clinical and audiological outcomes. Coupling the floating mass transducer to the short process of the incus is a good surgical option, especially when the long process and the oval or round window are inaccessible. PMID- 26991878 TI - Evaluation and comparison of type I tympanoplasty efficacy and histopathological changes to the tympanic membrane in dry and wet ear: a prospective study. PMID- 26991879 TI - Evaluation and comparison of type I tympanoplasty efficacy and histopathological changes to the tympanic membrane in dry and wet ear: a prospective study. PMID- 26991880 TI - First Steps in the Aggregation Process of Copolymers Based on Thymine Monomers: Characterization by Molecular Dynamics Simulations and Atomic Force Microscopy. AB - Atomistic molecular dynamic simulations were performed to study the structure of isolated VBT-VBA (vinylbenzylthymine-vinylbenzyltriethylammonium chloride) copolymer chains in water at different monomeric species ratios (1:1 and 1:4). The geometric parameters of the structure that the copolymers form in equilibrium together with the basic interactions that stabilize them were determined. Atomic force microscopy (AFM) measurements of dried diluted concentrations of the two copolymers onto highly oriented pyrolytic graphite (HOPG) substrates were carried out to study their aggregation arrangement. The experiments show that both copolymers arrange in fiber-like structures. Comparing the diameters predicted by the simulation results and those obtained by AFM, it can be concluded that individual copolymers arrange in bunches of two chains, stabilized by contra-ions copolymer interactions for the 1:1 copolymerization ratio at the ionic strength of our samples. In contrast, for the 1:4 system the individual copolymer chains do not aggregate in bunches. These results remark the relevance of the copolymerization ratio and ionic strength of the solvent in the mesoscopic structure of these materials. PMID- 26991881 TI - Effects of the spatial repellent metofluthrin on landing rates of outdoor biting anophelines in Cambodia, Southeast Asia. AB - The emergence of artemisinin-resistant malaria in Southeast Asia is a major problem. The fact that many people become infected with malaria when they are outside has prompted the development of 'spatial' rather than topical repellents. The respective effects of one or four slow-release emanators of metofluthrin, a pyrethroid, were tested in Pailin, Pursat and Koh Kong, Cambodia. Numbers of mosquitoes counted in outdoor landing catches when one or four emanators were suspended close to the collector were compared with control collections. In Pailin, the effects of emanators on catches in Furvela tent traps and Centers for Disease Control (CDC) light traps suspended underneath houses were also investigated. Rate ratios were used to determine differences. A total of 29 255 mosquitoes were collected over 2934 h of landing collections, 87 nights of tent trapping and 81 nights of light trap capture. In Pailin, landing rates were reduced by 48% by a single emanator and by 67% by four emanators (P < 0.001). Similar reductions were observed in the number of mosquitoes collected in tent traps and the number of anophelines only collected in light traps. Results were similar in Pursat, but, for unknown reasons, those in Koh Kong showed no difference between control and metofluthrin collections (P > 0.05). These findings suggest that although the product can produce a significant effect, it requires further improvement. PMID- 26991882 TI - Morphological and nanomechanical changes in mechanosensitive endothelial cells induced by colloidal AFM probes. AB - Mechanotransduction is one of the main properties of endothelial cells (ECs) phenotype. Hemodynamic forces like flow-generated endothelial shear stress play a fundamental role in ECs cytoskeletal remodeling and activate signaling cascades in ECs. AFM methods are widely used to characterize morphology as well as mechanical properties of cells. In both cases AFM probes directly interact with cell surface exerting mechanical forces on the cellular membrane, which in turn may stimulate mechanosensitive receptors present in EC. This article presents examples of how the colloidal AFM probes influence ECs during multiple scans. The results revealed that multiple scans of the ECs significantly influenced the morphology and elasticity of cells. Moreover, changes in the cell shape and mechanical properties were dependent on the scan direction (across or along the main axis of the cell). Multiple scans with a colloidal probe leaded to reorientation of the cell main axis and this effect was similar to the action of the shear stress induced by flow conditions. Furthermore, the correlation between the tip-induced modification of the cell properties and the remodeling of the cell's glycocalyx was observed. SCANNING 38:654-664, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991883 TI - Leksell Gamma Knife treatment for pilocytic astrocytomas: long-term results. AB - OBJECTIVE The purpose of this study was to evaluate long-term treatment results, radiation-related toxicity, and prognostic factors for the progression-free survival (PFS) of patients with pilocytic astrocytomas treated by means of stereotactic radiosurgery with a Leksell Gamma Knife. METHODS A total of 25 patients with pilocytic astrocytomas underwent Gamma Knife surgery during the period 1992-2002. The median target volume was 2700 mm(3) (range 205-25,000 mm(3)). The 18 patients treated with 5 daily fractions received a median minimum target dose of 25 Gy. Doses for the 2 patients treated with 10 fractions over 5 days (2 fractions delivered on the same day at least 6 hours apart) were 23 and 28 Gy. For the 5 patients treated with a single fraction, the minimum target dose ranged from 13 to 20 Gy (median 16 Gy). RESULTS Complete regression occurred in 10 patients (40%) and partial regression in 10 patients (40%). The 10-year overall survival rate was 96% and the 10-year PFS rate was 80%. Target volume appeared to be a significant prognostic factor for PFS (p = 0.037). Temporary Grade 3 toxicity appeared in 2 patients (8%), and these patients were treated with corticosteroids for 2 months. Permanent Grade 4 toxicity appeared in 2 patients (8%) and was associated with neurocognitive dysfunction. In these 2 individuals, the neurocognitive dysfunction was also felt to be in part the result of the additional therapeutic interventions (4 in one case and 6 in the other) required to achieve durable control of their tumors. CONCLUSIONS Radiosurgery represents an alternative treatment modality for small residual or recurrent volumes of pilocytic astrocytomas and provides long-term local control. Target volume appears to be the most important factor affecting PFS. PMID- 26991884 TI - Letter to the Editor: Intrathecal baclofen trials: complications and positive yield in a pediatric cohort. PMID- 26991885 TI - Letter to the Editor: Arterial spin labeling in evaluation of venous drainage pattern in brain arteriovenous malformations. PMID- 26991886 TI - Prognostic value of neutrophil-to-lymphocyte ratio in predicting long-term mortality in patients with ischemic and nonischemic heart failure. AB - INTRODUCTION: Previous studies have shown that an elevated neutrophil-to lymphocyte ratio (NLR) was associated with a poorer long-term prognosis in patients with heart failure (HF). OBJECTIVES: We aimed to study the predictive value of the NLR in patients with left ventricular ejection fraction of 35% or lower. The second objective was to establish whether the NLR has the same prognostic value in patients with ischemic and nonischemic HF. PATIENTS AND METHODS: The study group consisted of a cohort of patients with HF (1387 men, 347 women; median age, 61 years) from the prospective COMMIT-HF registry. The primary endpoint was all-cause mortality. Patients were divided into tertiles based on the NLR values on admission. The first (low), second (medium), and third (high) tertiles were defined as NLR <=2.04 (n = 578), NLR 2.05-3.1 (n = 578) and NLR >3.1 (n = 578), respectively. RESULTS: During long-term follow-up, 443 deaths were reported. The 12-month mortality in patients in the third NLR tertile was almost 3-fold higher compared with those in the first tertile (7.61% vs 20.07%; P <0.001). In a multivariate analysis, the NLR was an independent factor of mortality (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.82-2.92; P <0.0001). In addition, the multivariate analysis revealed that the third NLR tertile in the ischemic HF group was an independent factor related to longterm mortality (HR, 1.51; 95% CI, 1.11-2.04; P = 0.008). In the nonischemic HF group, the influence of the NLR on long-term survival was not confirmed. CONCLUSIONS: The association between the NLR and the risk of death in long-term follow-up was confirmed only in the subgroup of patients with ischemic HF. PMID- 26991887 TI - Membrane mediated development of the vertebrate blood-gas-barrier. AB - During embryonic lung development, establishment of the gas-exchanging units is guided by epithelial tubes lined by columnar cells. Ultimately, a thin blood-gas barrier (BGB) is established and forms the interface for efficient gas exchange. This thin BGB is achieved through processes, which entail lowering of tight junctions, stretching, and thinning in mammals. In birds the processes are termed peremerecytosis, if they involve cell squeezing and constriction, or secarecytosis, if they entail cutting cells to size. In peremerecytosis, cells constrict at a point below the protruding apical part, resulting in fusion of the opposing membranes and discharge of the aposome, or the cell may be squeezed by the more endowed cognate neighbors. Secarecytosis may entail formation of double membranes below the aposome, subsequent unzipping and discharge of the aposome, or vesicles form below the aposome, fuse in a bilateral manner, and release the aposome. These processes occur within limited developmental windows, and are mediated through cell membranes that appear to be of intracellular in origin. In addition, basement membranes (BM) play pivotal roles in differentiation of the epithelial and endothelial layers of the BGB. Laminins found in the BM are particularly important in the signaling pathways that result in formation of squamous pneumocytes and pulmonary capillaries, the two major components of the BGB. Some information exists on the contribution by BM to BGB formation, but little is known regarding the molecules that drive peremerecytosis, or even the origins and composition of the double and vesicular membranes involved in secarecytosis. PMID- 26991888 TI - Long-Term Outcomes and Durability of the Mitroflow Aortic Bioprosthesis. AB - BACKGROUND: This study aims to determine the incidence and causes of structural valve deterioration (SVD) among all models of Mitroflow bioprostheses (A12/LX/DL), as well as to define their long-term clinical and hemodynamic performance. METHODS AND RESULTS: We retrospectively reviewed a series of 1023 patients who underwent aortic valve replacement with Mitroflow bioprostheses between 2001 and 2014. A small aortic root was found in 22.4% of patients. There were two cases of severe patient-prosthesis mismatch. Only 31 patients developed SVD. The rate of incidence was 8.1 cases per 1000 patient-years. Cumulative incidence of SVD was 1.4% and 3% at five and 10 years, respectively. Freedom from SVD was 97.4% and 88.2% at five and 10 years, respectively. Anticalcification phospholipid reduction treatment (PRT) for model DL was a protective factor for SVD. Multivariable analysis confirmed age <70 years and use of 19 mm valve as independent predictors of SVD. Cumulative survival was 76.6% at five years and 42.3% at 10 years (mean follow-up 3.8 +/- 3.1 years). In multivariable analysis, neither the use of small aortic prosthesis (p = 0.18) nor the occurrence of SVD (p = 0.85) was found to be independent predictors of long-term survival. CONCLUSIONS: Mitroflow valves demonstrate an acceptable rate of SVD and satisfactory long-term hemodynamic performance, particularly in patients with small aortic roots, age >70 years, and cases with severe left ventricular hypertrophy. PRT might contribute to improved long-term durability. doi: 10.1111/jocs.12726 (J Card Surg 2016;31:264-273). PMID- 26991889 TI - Baseline medical comorbidities in adults randomized in the STRIDE trial for psychostimulant use disorders. AB - BACKGROUND AND OBJECTIVES: Rates of medical illnesses may be higher among individuals with substance use disorders, complicating their care. This study aimed to expand the understanding of other medical conditions in treatment seeking adults with stimulant use disorder (SUD) using data from Stimulant Reduction Intervention using Dose Exercise (STRIDE), a randomized, multisite trial investigating exercise augmentation of treatment as usual. METHODS: Utilizing STRIDE baseline data, we examined demographic and clinical characteristics based on the number of self-reported diagnosed medical conditions among participants meeting eligibility criteria (passing medical screening exam and maximal exercise test, non-opioid dependent, no concomitant beta blocker, or opioid replacement therapy). RESULTS: The majority (59%) of study participants (N = 302, mean age all participants = 39 years) did not report any history of other medical problems. Those with two or more conditions were older (mean age 46 years), reported more pain and worse physical functioning, and more psychiatric disorders (average 1.44). Hypertension was more common among participants with cocaine use disorders only (present in 16%) and liver disease was more common in those with cocaine plus other stimulant use disorders (present in 7%). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: In this sample, patients with SUD were in surprisingly good health. A subpopulation had an overall higher burden of illness with worsened physical and psychiatric functioning. Provision of coordinated care may optimize treatment outcomes for patients based on medical comorbidity burden as well as type of drug abused, although these conclusions should be considered preliminary as they are based on self-reported data. PMID- 26991890 TI - Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials. AB - OBJECTIVE: To summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment. DESIGN: Data from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level. SETTING: University affiliated reproductive medicine unit. PATIENTS: Subcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30 kg/m2. INTERVENTIONS: Subcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients. MAIN OUTCOME MEASURES: Ongoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk. RESULTS: The administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk. CONCLUSION: No statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support. PMID- 26991892 TI - In situ microscopy reveals reversible cell wall swelling in kelp sieve tubes: one mechanism for turgor generation and flow control? AB - Kelps, brown algae (Phaeophyceae) of the order Laminariales, possess sieve tubes for the symplasmic long-distance transport of photoassimilates that are evolutionarily unrelated but structurally similar to the tubes in the phloem of vascular plants. We visualized sieve tube structure and wound responses in fully functional, intact Bull Kelp (Nereocystis luetkeana [K. Mertens] Postels & Ruprecht 1840). In injured tubes, apparent slime plugs formed but were unlikely to cause sieve tube occlusion as they assembled at the downstream side of sieve plates. Cell walls expanded massively in the radial direction, reducing the volume of the wounded sieve elements by up to 90%. Ultrastructural examination showed that a layer of the immediate cell wall characterized by circumferential cellulose fibrils was responsible for swelling and suggested that alginates, abundant gelatinous polymers of the cell wall matrix, were involved. Wall swelling was rapid, reversible and depended on intracellular pressure, as demonstrated by pressure-injection of silicon oil. Our results revive the concept of turgor generation and buffering by swelling cell walls, which had fallen into oblivion over the last century. Because sieve tube transport is pressure-driven and controlled physically by tube diameter, a regulatory role of wall swelling in photoassimilate distribution is implied in kelps. PMID- 26991891 TI - Assessing the influence of component processing and donor characteristics on quality of red cell concentrates using quality control data. AB - BACKGROUND AND OBJECTIVES: Quality control (QC) data collected by blood services are used to monitor production and to ensure compliance with regulatory standards. We demonstrate how analysis of quality control data can be used to highlight the sources of variability within red cell concentrates (RCCs). MATERIALS AND METHODS: We merged Canadian Blood Services QC data with manufacturing and donor records for 28 227 RCC between June 2011 and October 2014. Units were categorized based on processing method, bag manufacturer, donor age and donor sex, then assessed based on product characteristics: haemolysis and haemoglobin levels, unit volume, leucocyte count and haematocrit. RESULTS: Buffy coat method (top/bottom)-processed units exhibited lower haemolysis than units processed using the whole-blood filtration method (top/top). Units from female donors exhibited lower haemolysis than male donations. Processing method influenced unit volume and the ratio of additive solution to residual plasma. CONCLUSIONS: Stored red blood cell characteristics are influenced by prestorage processing and donor factors. Understanding the relationship between processing, donors and RCC quality will help blood services to ensure the safety of transfused products. PMID- 26991893 TI - Single Heteroatom Fine-Tuning of the Emissive Properties in Organoboron Complexes with 7-(Azaheteroaryl)indole Systems. AB - The application of organoboron compounds as light-absorbing or light-emitting species in areas as relevant as organic electronics or biomedicine has motivated the search for new materials which contribute to the progress of those applications. This article reports the synthesis of four-coordinate boron complexes based on the unexplored 7-(azaheteroaryl)indole ligands. An easy synthetic approach has enabled the fine-tuning of the electronic structure of the organoboron species by modifying a heteroaromatic component in the conjugated system. Furthermore, a comprehensive characterization by X-ray diffraction, absorption and emission spectroscopy, both in solution and in the solid state, cyclic voltammetry, and computational methods has evidenced the utility of this simple strategy. Large Stokes shifts have been achieved in solid thin-films which show a range of emitted light from blue to orange. The synthesized compounds have been used as biocompatible fluorophores in cell bioimaging. PMID- 26991895 TI - Two adult cases of massively calcified low-grade glioma: expanding clinical spectrum of an emerging entity. PMID- 26991894 TI - Transcriptome Analysis Provides Insights into the Mechanisms Underlying Wheat Plant Resistance to Stripe Rust at the Adult Plant Stage. AB - Stripe rust (or yellow rust), which is caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating wheat diseases worldwide. The wheat cultivar Xingzi 9104 (XZ) is an elite wheat germplasm that possesses adult plant resistance (APR), which is non-race-specific and durable. Thus, to better understand the mechanism underlying APR, we performed transcriptome sequencing of wheat seedlings and adult plants without Pst infection, and a total of 157,689 unigenes were obtained as a reference. In total, 2,666, 783 and 2,587 differentially expressed genes (DEGs) were found to be up- or down-regulated after Pst infection at 24, 48 and 120 hours post-inoculation (hpi), respectively, based on a comparison of Pst- and mock-infected plants. Among these unigenes, the temporal pattern of the up-regulated unigenes exhibited transient expression patterns during Pst infection, as determined through a Gene Ontology (GO) enrichment analysis. In addition, a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that many biological processes, including phenylpropanoid biosynthesis, reactive oxygen species, photosynthesis and thiamine metabolism, which mainly control the mechanisms of lignification, reactive oxygen species and sugar, respectively, are involved in APR. In particular, the continuous accumulation of reactive oxygen species may potentially contribute to the ability of the adult plant to inhibit fungal growth and development. To validate the bioinformatics results, 6 candidate genes were selected for further functional identification using the virus-induced gene silencing (VIGS) system, and 4 candidate genes likely contribute to plant resistance against Pst infection. Our study provides new information concerning the transcriptional changes that occur during the Pst-wheat interaction at the adult stage and will help further our understanding of the detailed mechanisms underlying APR to Pst. PMID- 26991896 TI - Sickle-Cell Disease in Nigerian Children: Parental Knowledge and Laboratory Results. AB - BACKGROUND: Sickle-cell disease (SCD) is the most common inherited genetic disorder in sub-Saharan Africa, and it is associated with early mortality and lifelong morbidity. Early diagnosis is essential for instituting appropriate care and preventive therapy. OBJECTIVE: To compare parental knowledge or perception of their offspring's hemoglobin phenotype prior to testing and actual validated laboratory test results. METHODS: In a prospective community-based survey, we assessed parental knowledge of their children's hemoglobin phenotype and corroborated this with the results from a laboratory confirmatory test determined by high-performance liquid chromatography. RESULTS: We screened 10,126 children aged less than 5 years. A total of 163 (1.6%) parents indicated that their offspring had been previously tested and had knowledge of the child's hemoglobin genotype. However, 51 (31.2%) of 163 parents of children who had been previously tested did not know the result of their offspring's test, and 18 (35.3%) of these 51 children were found to have SCD. Of those who claimed previous knowledge, 25 (15.3%) of 163 reported incorrect results. Overall, we identified 272 (2.76%) new cases from 9,963 children who had not been previously tested. CONCLUSION: There is the need to promote public awareness about SCD and the benefit of early diagnosis, quality assurance in laboratory diagnosis and institution of sustainable patient care pathways. PMID- 26991898 TI - IL-10-Producing Regulatory B Cells Are Decreased in Patients with Common Variable Immunodeficiency. AB - Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults. CVID patients often present changes in the frequency and function of B lymphocytes, reduced number of Treg cells, chronic immune activation, recurrent infections, high incidence of autoimmunity and increased risk for malignancies. We hypothesized that the frequency of B10 cells would be diminished in CVID patients because these cells play an important role in the development of Treg cells and in the control of T cell activation and autoimmunity. Therefore, we evaluated the frequency of B10 cells in CVID patients and correlated it with different clinical and immunological characteristics of this disease. Forty-two CVID patients and 17 healthy controls were recruited for this study. Cryopreserved PBMCs were used for analysis of T cell activation, frequency of Treg cells and characterization of B10 cells by flow cytometry. IL 10 production by sorted B cells culture and plasma sCD14 were determined by ELISA. We found that CVID patients presented decreased frequency of IL-10 producing CD24hiCD38hi B cells in different cell culture conditions and decreased frequency of IL-10-producing CD24hiCD27+ B cells stimulated with CpG+PIB. Moreover, we found that CVID patients presented lower secretion of IL-10 by sorting-purified B cells when compared to healthy controls. The frequency of B10 cells had no correlation with autoimmunity, immune activation and Treg cells in CVID patients. This work suggests that CVID patients have a compromised regulatory B cell compartment which is not correlated with clinical and immunological characteristics presented by these individuals. PMID- 26991899 TI - Hierarchically Mesostructured Polyisobutylene-Based Ionic Liquids. AB - The formation and design of a hierarchically nanostructured poly(isobutylene) based ionic liquid (PIB-ILs) is reported, displaying assembly into classical multiplets and an additional ordering of the aromatic counteranions. Three PIB ILs (Mn = 3600 and 8600 g mol(-1) ), bearing imidazolium (1a), N methylpyrrolidinium (1b), and triethylammonium cations (1c) together with the aromatic 2-(methylthio)benzoate anion are prepared via a combination of living carbocationic polymerization, "click" reactions and subsequent anion metathesis. The morphology of the novel PIB-ILs as well as its temperature-dependent behavior has been studied via small angle X-ray scattering, displaying two different transition temperatures: one originating from ordering of micelles within a cylinder, and the second from cylinder-cylinder arrangement. Furthermore, the incorporation of an aromatic, rigid, and bulky 2-(methylthio)benzoate anion into the PIB-ILs effects the formation of an internal assembly consisting of stacked cylindrical structures, composed from the mesoscale ordering of ionic "multiplets" characteristic for classical ionomers and from the typical distance of the cylinders themselves. PMID- 26991900 TI - Survey of Obstetric Care and Cesarean Delivery Rates in Shanghai, China. AB - BACKGROUND: China has one of the highest cesarean delivery rates in the world, with most cesareans done without indication. METHODS: Observation of how perinatal care is delivered in a range of Shanghai hospitals was done to gain insight into the 50 percent cesarean delivery rate. A mixed methods approach combined a descriptive structured survey of obstetric services with standardized interview with obstetricians and qualitative observation of obstetric services in six different Shanghai obstetric facilities. RESULTS: The volume was extremely high: physicians in public hospitals routinely saw up to 80-120 prenatal patients per day. Frequent prenatal testing substituted for time spent in patient-doctor interactions. Family members were not allowed in delivery wards where women labored alone. Obstetrics services had low levels of nursing support and anesthesia for labor. Physical space favored rapid surgical turnover over longer labor. Physicians reported practical incentives to perform cesarean sections. DISCUSSION: Cesarean delivery was an efficient way to move patients through the systems observed, given the staffing and physical limitations of the public facilities. Physicians reported that patients and families perceived cesarean delivery as safer. Physicians also reported fear of charges of malpractice, for which they might be found to be financially liable or in physical danger. Societal expectations are high, and in a "one child" society, perception that cesarean section was safer may also have driven cesarean rates. Given the end of the One Child Policy, the preference for cesarean delivery may change. PMID- 26991897 TI - Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2. AB - OBJECTIVE: The objective of this study was to identify new causes of Charcot Marie-Tooth (CMT) disease in patients with autosomal-recessive (AR) CMT. METHODS: To efficiently identify novel causative genes for AR-CMT, we analyzed 303 unrelated Japanese patients with CMT using whole-exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation. RESULTS: We identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta-amyloid (Abeta) degrading enzymes. All patients had a similar phenotype consistent with late onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss-of function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Abeta in Pittsburgh compound-B positron emission tomography imaging. INTERPRETATION: Our results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T. A loss-of-function MME mutation did not cause early-onset Alzheimer's disease. Identifying the MME mutation responsible for AR CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT. PMID- 26991901 TI - Novel Duplicate Address Detection with Hash Function. AB - Duplicate address detection (DAD) is an important component of the address resolution protocol (ARP) and the neighbor discovery protocol (NDP). DAD determines whether an IP address is in conflict with other nodes. In traditional DAD, the target address to be detected is broadcast through the network, which provides convenience for malicious nodes to attack. A malicious node can send a spoofing reply to prevent the address configuration of a normal node, and thus, a denial-of-service attack is launched. This study proposes a hash method to hide the target address in DAD, which prevents an attack node from launching destination attacks. If the address of a normal node is identical to the detection address, then its hash value should be the same as the "Hash_64" field in the neighboring solicitation message. Consequently, DAD can be successfully completed. This process is called DAD-h. Simulation results indicate that address configuration using DAD-h has a considerably higher success rate when under attack compared with traditional DAD. Comparative analysis shows that DAD-h does not require third-party devices and considerable computing resources; it also provides a lightweight security resolution. PMID- 26991903 TI - Combined plerixafor and granulocyte colony-stimulating factor for harvesting high dose hematopoietic stem cells: Possible niche for plerixafor use in pediatric patients. AB - PB is a source of HSC, especially for autologous HCT in solid tumors. However, there is a risk of failing to achieve the target number of SC after mobilization with growth factors alone in patients who were heavily pretreated with chemotherapy or those in need for tandem transplants. SC were harvested from seven pediatric patients with solid tumors who were in need of autologous HCT following combination GCSF and plerixafor. Six of them received plerixafor after failing to achieve enough SC with GCSF only, while the seventh patient received the combined protocol upfront. All seven patients achieved the target number of SC according to their treatment protocol. There were no adverse events. All patients underwent autologous HCT using the harvested HSC and achieved full engraftment. A protocol for harvesting autologous HCT using GCSF and plerixafor is feasible and safe in children with solid tumors who had been heavily pretreated with chemotherapy or needed tandem transplants. PMID- 26991902 TI - Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation. AB - AIM: The aim of the present study was to characterize the pharmacokinetic profile of corifollitropin alfa and examine the relationships between dose, intrinsic factors [body weight, body mass index (BMI), age and race] and corifollitropin alfa pharmacokinetics. METHODS: Data from five phase II and III clinical trials of corifollitropin alfa were evaluated. All subjects included in the analysis received 60 - 180 MUg corifollitropin alfa for controlled ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol followed by daily recombinant follicle stimulating hormone (rFSH) from day 8 onwards. Serum corifollitropin alfa levels (across the entire range of treatment) and total follicle stimulating hormone immunoreactivity levels (up to the start of rFSH treatment) were indicators of drug exposure. The analyses were performed using a nonlinear mixed-effects modelling approach. RESULTS: A total of 2630 subjects were treated with corifollitropin alfa, and 2557 subjects were evaluable for analysis. Body weight, BMI and race (Asian and Black vs. Caucasian) were significant determinants of corifollitropin alfa exposure. Dose-normalized corifollitropin alfa exposure was ~89% higher in women with a body weight of 50 kg vs. 90 kg (in subjects with a similar BMI of 24 kg m(-2) ); 14% higher in women with a BMI of 18 kg m(-2) vs. 32 kg m(-2) (provided they were of similar body weight); and ~15.7% lower in Asian subjects and 13% higher in Black subjects vs. Caucasian subjects. CONCLUSIONS: Body weight was the major determinant of corifollitropin alfa exposure; BMI and race (Asian and Black) were also determinants but to a lesser extent and without associated effects on clinical outcomes. Corifollitropin alfa dose adjustment is indicated, based on body weight but not for BMI or race. These recommendations are consistent with the product label. PMID- 26991904 TI - Gross Nitrogen Mineralization in Surface Sediments of the Yangtze Estuary. AB - Nitrogen mineralization is a key biogeochemical process transforming organic nitrogen to inorganic nitrogen in estuarine and coastal sediments. Although sedimentary nitrogen mineralization is an important internal driver for aquatic eutrophication, few studies have investigated sedimentary nitrogen mineralization in these environments. Sediment-slurry incubation experiments combined with 15N isotope dilution technique were conducted to quantify the potential rates of nitrogen mineralization in surface sediments of the Yangtze Estuary. The gross nitrogen mineralization (GNM) rates ranged from 0.02 to 5.13 mg N kg(-1) d(-1) in surface sediments of the study area. The GNM rates were generally higher in summer than in winter, and the relative high rates were detected mainly at sites near the north branch and frontal edge of this estuary. The spatial and temporal distributions of GNM rates were observed to depend largely on temperature, salinity, sedimentary organic carbon and nitrogen contents, and extracellular enzyme (urease and L-glutaminase) activities. The total mineralized nitrogen in the sediments of the Yangtze Estuary was estimated to be about 6.17 * 10(5) t N yr(-1), and approximately 37% of it was retained in the estuary. Assuming the retained mineralized nitrogen is totally released from the sediments into the water column, which contributed 12-15% of total dissolved inorganic nitrogen (DIN) sources in this study area. This result indicated that the mineralization process is a significant internal nitrogen source for the overlying water of the Yangtze Estuary, and thus may contribute to the estuarine and coastal eutrophication. PMID- 26991905 TI - Factors affecting N-terminal pro-brain natriuretic peptide elevation in the acute phase of Kawasaki disease. AB - BACKGROUND: The aim of this study was to investigate the clinical significance and factors that affect N-terminal pro-brain natriuretic peptide (NT-proBNP) elevation in the acute phase of Kawasaki disease (KD) despite the absence of apparent cardiac complications. METHODS: The laboratory and echocardiography results of 44 KD patients in the acute and subacute phases were reviewed. RESULTS: With preserved cardiac function, median NT-proBNP was significantly elevated in the acute phase compared with the subacute phase (343 pg/mL, IQR, 162 1182 pg/mL vs 98 pg/mL, IQR, 61-205 pg/mL, respectively; P < 0.0001). The respective levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor (sTNFR)1, and sTNFR2 were also significantly elevated in the acute phase compared with the subacute phase: TNF-alpha, 3.3 pg/mL (IQR, 2.6-4.8 pg/mL) versus 2.4 pg/mL (IQR 1.9-4.0 pg/mL; P < 0.01), sTNFR1, 2741 pg/mL (IQR, 2080-3183 pg/mL) versus 976 pg/mL (IQR, 814-1247 pg/mL; P < 0.0001), sTNFR2, 5644 pg/mL (IQR, 4693 7520 pg/mL) versus 3169 pg/mL (IQR, 2132-3878 pg/mL; P < 0.0001). Log-transformed NT-proBNP was correlated with TNF-alpha (r = 0.29, P = 0.056), sTNFR1 (r = 0.60, P < 0.0001), and sTNFR2 (r = 0.65, P < 0.0001). TNF-alpha was correlated with sTNFR1 (r = 0.35, P = 0.02) and sTNFR2 (r = 0.51, P < 0.001). CONCLUSION: Tumor necrosis factor-alpha may cause NT-proBNP elevation in the acute phase of KD, and NT-proBNP level may be an indicator of TNF-alpha activity. PMID- 26991906 TI - Spectroscopic, electrochemical and molecular docking studies of dothiepin and doxepin with bovine serum albumin and DNA base. AB - The interaction of dothiepin (DOT) and doxepin (DOX) with bovine serum albumin (BSA) and a DNA base (adenine) was studied using UV-visible, fluorescence, attenuated total reflection-infra-red (ATR-IR), cyclic voltammetry and molecular docking methods. Strong fluorescence quenching was observed upon interaction of DOT and DOX with BSA/adenine and the mechanism suggested static quenching. Hydrophobic and hydrogen bonding interactions were the predominant intermolecular forces needed to stabilize the copolymer. Upon addition of the drugs: (i) the tautomeric equilibrium structure of the adenine was changed; and (ii) the oxidation and the reduction peaks of the adenine/BSA interaction shifted towards high and low potentials, respectively. In ATR-IR, the band shift of amides I and II indicated a change in secondary structure of BSA upon binding to DOT and DOX drugs. The reduction in voltammetric current in the presence of BSA/adenine was attributed to slow diffusion of BSA/adenine binding with DOX/DOT. The docking method indicated that the drug moiety interacted with the BSA molecule. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991907 TI - PI3K-AKT-mTOR pathway proteins are differently expressed in oral carcinogenesis. AB - BACKGROUND: PI3K-AKT-mTOR signaling pathway is associated with several cellular functions and is frequently changed in several malignancies. The aim of this study was to characterize the immunohistochemical expression pattern of components in PI3K-AKT-mTOR signaling pathway in oral epithelial dysplasia (OED), comparing to oral squamous cell carcinoma (OSCC) and non-dysplastic oral tissues (NDOT). METHODS: A total of 186 cases of NDOT, OED and OSCC were retrieved. Nuclear staining and cytoplasmic staining of the keratinocytes were considered positive, and the percentage of positive cells was calculated. RESULTS: Increased immunoreactivity from NDOT to OED and OSCC was seen for all proteins. In NDOT cases, positivity was found only for pS6 (52.9%) and p4EBP1 (13.5%). In OED, immunoreactivity was observed for pAKT (62.2%), pmTOR (28.6%), pS6 (70.8%), and p4EBP1 (42.9%). In OSCC cases, immunoreactivity was found for pAKT (83.3%), pmTOR (50%), pS6 (77.4%), and p4EBP1 (50%). The pAKT and pmTOR expression was higher in OED (<0.001, Fisher's exact test) and OSCC (<0.001, Fisher's exact test). CONCLUSION: Our study demonstrated higher pAKT and pmTOR expression during carcinogenesis of oral mucosa, differing considerably among OED and OSCC specimens when compared to NDOT. These proteins can be considered potential diagnostic markers for early detection of cancer. PMID- 26991909 TI - Identification, characterization and functional analysis of a chitin synthase gene in the brown citrus aphid, Toxoptera citricida (Hemiptera, Aphididae). AB - Chitin synthase (CHS) is a crucial enzyme involved in the final step of the insect chitin biosynthetic pathway. In this study, we cloned the full-length cDNA sequence of a chitin synthase gene (TCiCHS) from the brown citrus aphid, Toxoptera citricida, an important citrus pest and the main vector of citrus tristeza virus worldwide. TCiCHS was expressed during the entire lifecycle and in all insect tissues examined. Expression was highest in first-second-instar nymphs, nymph-adult transitions and in the abdomen (6.7-fold higher than head). Embryos had a higher expression level than the integument. Fourth-instar nymphs were exposed to 5 and 500 mg/l concentrations of the chitin synthesis inhibitor diflubenzuron (DFB) for 48 h and had the highest mortality at the 500 mg/l concentration. The mRNA expression levels of TCiCHS were significantly enhanced upon the exposure of nymphs to both low and high DFB concentrations. Silencing of TCiCHS occurred through plant-mediated double-stranded RNA (dsRNA) feeding. Most dsRNA-fed nymphs were unable to moult to the next stage, and the expression of TCiCHS decreased 48% compared with controls. These results demonstrate that TCiCHS plays an important role in nymph to adult development, is possibly help identify molecular targets for To. citricida control. PMID- 26991908 TI - Biological Status and Dietary Intakes of Iron, Zinc and Vitamin A among Women and Preschool Children in Rural Burkina Faso. AB - BACKGROUND: Food-based approaches such as biofortification are meant to sustainably address micronutrient deficiencies in poor settings. Knowing more about micronutrient intakes and deficiencies is a prerequisite to designing and evaluating interventions. OBJECTIVE: The objectives of the study were to assess biological status and dietary intakes of iron, zinc and vitamin A among women and children aged 36-59 months in rural Burkina Faso and to study relationships between intake and status to better inform future food-based interventions. DESIGN: A cross-sectional survey was carried out in two rural provinces of Burkina Faso on a random cluster sample of 480 mother-child pairs. Dietary data was obtained by 24-hour recalls repeated on a random sub-selection of 37.5% of subjects to allow calculation of nutrient's probability of adequacy (PA). Biomarkers were measured on a sub-sample of 180 mother-child pairs. Blood samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptors (sTfR), C-reactive protein, alpha-1-glycoprotein, serum zinc concentration (SZnC) and retinol. For each micronutrient the relationship between biomarker and dietary intake was investigated by multiple linear regression models accounting for inflammatory biomarkers. RESULTS: Mean PA for iron, zinc and vitamin A was 0.49, 0.87 and 0.21 among women and 0.61, 0.95 and 0.33 among children, respectively. Prevalence of anemia, corrected low serum ferritin and high sTfR was 37.6%, 4.0% and 77.5% among women and 72.1%, 1.5% and 87.6% among children, respectively. Prevalence of low SZnC and corrected low serum retinol was 39.4% and 12.0% among women and 63.7% and 24.8% among children, respectively. There was a tendency for a positive relationship between vitamin A intakes and serum retinol among women (beta = 0.0003, P = 0.06). Otherwise, no link was found between micronutrients biomarkers and intakes. CONCLUSION: Our study depicted different images of micronutrient deficiencies when based on dietary intakes or biomarkers results, thus highlighting the need for more suitable biomarkers and more precise measures of absorbable micronutrient intakes at the individual level. It thus points to challenges in the design and evaluation of future biofortification or other food-based interventions in rural areas of Burkina Faso. PMID- 26991910 TI - Combined Use of High Radiofrequency Disk Ablation, Annulus Modulation, and Manual Nucleotomy in a Patient with Extruded Disk Herniation. AB - Different minimally invasive procedures are used to treat lumbar disk herniation. It is important to differentiate these techniques due to their specific effects and the disparate technical issues associated with each. This report describes a successful case involving the use of mechanical decompression in conjunction with radiofrequency ablation to treat a patient with pain and neurological deficits due to an extruded disk hernia. CASE REPORT: A 43-year-old male had magnetic resonance imaging (MRI) demonstrating an extruded disk herniation in the left foraminal region, compression at the left spinal nerve root, and obliteration of the left foraminal entrance of the L5-S1 distribution. In the operating room, sufficient disk material was removed using grasping forceps, and then, the Disc FX system with a Trigger-Flex probe (Elliquence, Baldwin, NY, U.S.A.) was inserted. Modulation of the annulus was performed in bipolar hemo mode, and nucleus ablation was conducted in bipolar turbo mode within a 1.7-MHz frequency range. Among the available minimally invasive techniques, newly developed technologies may become important treatment options if they enable faster rehabilitation, lower rates of recurrence, shorter hospital stays, and reduced medical costs. PMID- 26991911 TI - 4D respiratory motion-compensated image reconstruction of free-breathing radial MR data with very high undersampling. AB - PURPOSE: To develop four-dimensional (4D) respiratory time-resolved MRI based on free-breathing acquisition of radial MR data with very high undersampling. METHODS: We propose the 4D joint motion-compensated high-dimensional total variation (4D joint MoCo-HDTV) algorithm, which alternates between motion compensated image reconstruction and artifact-robust motion estimation at multiple resolution levels. The algorithm is applied to radial MR data of the thorax and upper abdomen of 12 free-breathing subjects with acquisition times between 37 and 41 s and undersampling factors of 16.8. Resulting images are compared with compressed sensing-based 4D motion-adaptive spatio-temporal regularization (MASTeR) and 4D high-dimensional total variation (HDTV) reconstructions. RESULTS: For all subjects, 4D joint MoCo-HDTV achieves higher similarity in terms of normalized mutual information and cross-correlation than 4D MASTeR and 4D HDTV when compared with reference 4D gated gridding reconstructions with 8.4 +/- 1.1 times longer acquisition times. In a qualitative assessment of artifact level and image sharpness by two radiologists, 4D joint MoCo-HDTV reveals higher scores (P < 0.05) than 4D HDTV and 4D MASTeR at the same undersampling factor and the reference 4D gated gridding reconstructions, respectively. CONCLUSIONS: 4D joint MoCo-HDTV enables time-resolved image reconstruction of free-breathing radial MR data with undersampling factors of 16.8 while achieving low-streak artifact levels and high image sharpness. Magn Reson Med 77:1170-1183, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26991912 TI - Reduction of Cerebral and Corpus Callosum Volumes in Childhood-Onset Systemic Lupus Erythematosus: A Volumetric Magnetic Resonance Imaging Analysis. AB - OBJECTIVE: There have been few studies in which the prevalence of cerebral atrophy in childhood-onset systemic lupus erythematosus (SLE) was evaluated using magnetic resonance imaging (MRI) volumetric measurements. This study was undertaken to determine the prevalence of cerebral and corpus callosum atrophy in childhood-onset SLE and to determine the possible relationships between atrophy and clinical, laboratory, and treatment features of the disease. METHODS: We included 76 patients with childhood-onset SLE (69 female and 7 male; median age 16 years) and 66 age- and sex-matched healthy controls. Neurologic manifestations were analyzed according to the American College of Rheumatology (ACR) criteria. These SLE patients were further assessed for clinical and laboratory manifestations of SLE, disease activity (using the SLE Disease Activity Index), damage (using the Systemic Lupus International Collaborating Clinics/ACR Damage Index), and current and cumulative drug exposures. Scans were performed with a Philips 3.0T MRI scanner using a standardized protocol. RESULTS: Childhood-onset SLE patients had significantly smaller cerebral and corpus callosum volumes than controls (median cerebral volume 1,067.9 cm(3) versus 1,172.7 cm(3) and median corpus callosum volume 11.6 cm(3) versus 13.7 cm(3) ; P < 0.001). The presence of structural abnormalities was observed in 42 patients (55.3%) with childhood-onset SLE. The presence of cerebral atrophy was associated with anticardiolipin antibodies (aCL) (P = 0.02), anti-double-stranded DNA (P = 0.02), and cumulative corticosteroid dose (P = 0.04). The presence of corpus callosum atrophy was associated with low complement level (P = 0.006) and acute confusional state (P = 0.01). Serum levels of S100B or high molecular weight neurofilament and the presence of anti-ribosomal P were not associated with atrophy. CONCLUSION: Structural brain abnormalities were observed in 55.3% of the patients and were associated with neuropsychiatric manifestations, aCL, and corticosteroid use. To determine permanent neurologic damage, longitudinal studies must be conducted in these patients. PMID- 26991913 TI - Fuse and image enhancement. PMID- 26991914 TI - Current controversies in determining the main mechanisms of atrial fibrillation. AB - Despite considerable basic research into the mechanisms of atrial fibrillation (AF), not much progress has been made in the prognosis of patients with AF. With the exception of anticoagulant therapy, current treatments for AF still do not improve major cardiovascular outcomes. This may be due partly to the diverse aetiology of AF with increasingly more factors found to contribute to the arrhythmia. In addition, a strong increase has been seen in the technological complexity of the methods used to quantify the main pathophysiological alterations underlying the initiation and progression of AF. Because of the lack of standardization of the technological approaches currently used, the perception of basic mechanisms of AF varies widely in the scientific community. Areas of debate include the role of Ca(2+) -handling alterations associated with AF, the contribution and noninvasive assessment of the degree of atrial fibrosis, and the best techniques to identify electrophysiological drivers of AF. In this review, we will summarize the state of the art of these controversial topics and describe the diverse approaches to investigating and the scientific opinions on leading AF mechanisms. Finally, we will highlight the need for transparency in scientific reporting and standardization of terminology, assumptions, algorithms and experimental conditions used for the development of better AF therapies. PMID- 26991915 TI - Preliminary estimates of SEER cancer incidence for 2013. AB - BACKGROUND: This article presents a first look at rates and trends for cases in the Surveillance, Epidemiology, and End Results (SEER) program diagnosed through 2013 using the February 2015 submission, and a validation of rates and trends from the February 2014 submission using the subsequent November 2014 submission. To the authors' knowledge, this is the second time SEER has published trends based on the early February submission. Three new cancer sites were added: cervix, thyroid, and liver/ intrahepatic bile duct. METHODS: A reporting delay model adjusted for the undercount of cases, which is substantially larger for the February than the subsequent November submission, was used. Joinpoint regression methodology was used to assess trends. Delay-adjusted rates and trends were checked to assess validity between the February and November 2014 submissions. RESULTS: The validation of rates and trends from the February and November 2014 submissions demonstrated even better agreement than the previously reported comparison between the February and November 2013 submissions, thereby affording additional confidence that the delay-adjusted February submission data can be used to produce valid estimates of incidence trends. Trends for cases diagnosed through 2013 revealed more rapid declines in female colon and rectal cancer and prostate cancer. A plateau in female melanoma trends and a slowing of the increases in thyroid cancer and male liver/intrahepatic bile duct cancer trends were observed. CONCLUSIONS: Analysis of early cancer data submissions can provide a preliminary indication of differences in incidence trends with an additional year of data. Although the delay adjustment correction adjusts for underreporting of cases, caution should be exercised when interpreting the results in this early submission. Cancer 2016;122:1579-87. (c) 2016 American Cancer Society. PMID- 26991916 TI - Evaluating the effects of pollinator-mediated interactions using pollen transfer networks: evidence of widespread facilitation in south Andean plant communities. AB - Information about the relative importance of competitive or facilitative pollinator-mediated interactions in a multi-species context is limited. We studied interspecific pollen transfer (IPT) networks to evaluate quantity and quality effects of pollinator sharing among plant species on three high-Andean communities at 1600, 1800 and 2000 m a.s.l. To estimate the sign of the effects (positive, neutral or negative), the relation between conspecific and heterospecific pollen deposited on stigmas was analysed with GLMMs. Network analyses showed that communities were characterised by the presence of pollen hub donors and receptors. We inferred that facilitative and neutral pollinator mediated interactions among plants prevailed over competition. Thus, the benefits from pollinator sharing seem to outweigh the costs (i.e. heterospecific deposition and conspecific pollen loss). The largest proportion of facilitated species was found at the highest elevation community, suggesting that under unfavourable conditions for the pollination service and at lower plant densities facilitation can be more common. PMID- 26991917 TI - Effect of folic acid supplementation on cancer risk among adults with hypertension in China: A randomized clinical trial. AB - The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT and TT), were randomly assigned to receive double blind daily treatment with a single pill containing 10 mg enalapril and 0.8 mg folic acid(n = 10,348) or a pill containing 10 mg enalapril alone(n = 10,354). During a median treatment duration of 4.5 years, cancer occurred in 116 participants(1.12%) in the enalapril-folic acid group versus 116 participants(1.12%) in the enalapril group (HR, 1.00; 95%CI, 0.77-1.29). There was also no significant difference in the HRs for specific types of cancer(esophageal, gastric, breast, lung, colorectal, head and neck, liver and gynecologic cancer or lymphoma) or cancer mortality(HR, 1.05; 95%CI, 0.69-1.58). For participants not receiving folic acid treatment (enalapril only group), MTHFR 677 TT genotype was an independent predictor of total cancer risk compared to CC genotype (HR, 1.86; 95%CI, 1.07-3.22). Consistently, a beneficial effect was observed in participants with MTHFR TT genotype and low folate levels (<9.0 ng/mL; HR, 0.47; 95%CI, 0.24-0.94). There is no evidence that 0.8 mg daily folic acid supplementation can increase the risk of cancer incidence among adults with hypertension without history of stroke or MI in China. Our data suggest a protective effect in participants with MTHFR TT genotype and low folate levels. PMID- 26991919 TI - Utility of Ultrasonography of the Median Nerve With a High-Frequency Probe for the Diagnosis of Dialysis-Related Carpal Tunnel Syndrome. AB - This cross-sectional study aimed to determine the utility of ultrasonography with improved resolution using a high-frequency probe for dialysis-related carpal tunnel syndrome (CTS). This study targeted 125 hemodialysis patients at our hospital. A 12 MHz probe was placed on the carpal tunnel area to identify the median nerve. The compression rate of the nerve was calculated by measuring the smallest diameter of the compressed nerve and largest diameter of the unaffected part. To quantify CTS symptoms, we determined the presence of Tinel's sign, measured pinch strength, and used questionnaires to assess numbness and pain. The association of these clinical data with the compression rate was examined. Mean compression rate was 12.1 +/- 1.1%. The compression rate cutoff value for those positive with Tinel's sign was 25%, (sensitivity and specificity were 0.80 and 0.91, respectively), and that for those with a history of CTS surgery was 25% (sensitivity and specificity were 0.67 and 0.89, respectively). Multiple regression analysis identified duration of dialysis, beta2-microglobulin(beta2 Mg) concentration, positivity for Tinel's sign, history of CTS surgery, and pinch strength as independent compression rate determinants. Notably, compression rates were significantly higher in patients with a >=4-year duration of dialysis and a beta2-Mg level of 20 mg/L or more. The compression rate of the median nerve measured by an improved ultrasound device significantly correlated with clinical symptoms, medical history, and serological features associated with dialysis related CTS. Because ultrasonography is non-invasive, the examination might be a simple method especially for early diagnosis of dialysis-related CTS. PMID- 26991920 TI - Early outpatient follow-up and 30-day outcomes in patients hospitalized with cirrhosis. AB - Preventing readmission has been the focus of numerous quality improvement efforts across many conditions. Early outpatient follow-up has been proposed as the best mechanism for reducing readmissions. The extent to which early outpatient follow up averts readmission or improves outcomes in cirrhosis is not known. We evaluated the relationship between early outpatient follow-up and short-term readmission and mortality in patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis who were hospitalized with a liver-related diagnosis and discharged to home from 122 Veterans Administration hospitals between 2010 and 2013. We defined early follow-up as an outpatient visit with a clinician within 7 days after discharge. We propensity matched patients who received early visit with those who did not have any visit and examined the associations between early follow-up and all-cause readmission and mortality within 8-30 days after discharge. Of 25,217 patients hospitalized with cirrhosis, 8,123 (32.2%) had an early follow-up visit within 7 days of discharge. A total of 3,492 (13.8%) patients were readmitted and 1,185 (4.6%) died between 8 and 30 days after discharge. In the propensity-matched sample (N = 16,238), patients with early outpatient follow-up visit had a slightly higher risk of readmission (15.3% vs. 13.8%; hazard ratio [HR] =1.10; 95% confidence interval [CI] = 1.02-1.19), but significantly lower risk of mortality (3.2% vs. 5.2%; HR = 0.60; 95% CI = 0.51-0.70) than those without early visit. The findings persisted in several subgroup and sensitivity analyses. CONCLUSIONS: Early outpatient follow-up after discharge was associated with a small increase in readmissions but lower overall mortality in patients with cirrhosis. Transitional care may be effective in improving short-term outcomes in patients with cirrhosis, but readmission performance measures would miss this effect. (Hepatology 2016;64:569 581). PMID- 26991921 TI - Schwann-like cells differentiated from human dental pulp stem cells combined with a pulsed electromagnetic field can improve peripheral nerve regeneration. AB - The purpose of this study was to investigate the effect of Schwann-like cells combined with pulsed electromagnetic field (PEMF) on peripheral nerve regeneration. Schwann-like cells were derived from human dental pulp stem cells (hDPSCs) and verified with CD104, S100, glial fibrillary acidic protein (GFAP), laminin, and P75NTR immunocytochemistry. Gene expression of P75NTR and S100 were analyzed. Male Sprague-Dawley rats (200-250g, 6-week-old) were divided into seven groups (n = 10 each): control, sham, PEMF, hDPSCs, hDPSCs + PEMF, Schwann-like cells, Schwann-like cells + PEMF. Cells were transplanted (1 * 106 /10ul/rat) at crush-injury site or combined with PEMF (50 Hz, 1 h/day, 1 mT). Nerve regeneration was evaluated with functional test, histomorphometry and retrograde labelled neurons. Schwann-like cells expressed CD104, S100, GFAP, laminin, and p75 neurotrophin receptor (P75NTR ). P75NTR and S100 mRNA expression was highest in Schwann-like cells + PEMF group, which also showed increased Difference and Gap scores. Axons and retrograde labeled neurons increased in all treatment groups. Schwann-like cells, hDPSCs with or without PEMF, and PEMF only improved peripheral nerve regeneration. Schwann-like cells + PEMF showed highest regeneration ability; PEMF has additive effect on hDPSCs, Schwann-like cell in vitro and nerve regeneration ability after transplantation in vivo. Bioelectromagnetics. 37:163-174, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991922 TI - The International Frontal Sinus Anatomy Classification (IFAC) and Classification of the Extent of Endoscopic Frontal Sinus Surgery (EFSS). AB - The frontal recess and frontal sinus anatomy can vary from simple to complex. The variations in the anatomy of the frontal recess and frontal sinus are considerable but almost all variations can be classified if the various cell patterns are analyzed. This consensus document was developed to improve the ability of the surgeon to understand these possible variations, plan the surgery, and communicate these complexities when teaching or reporting outcomes. Once the surgeon understands the anatomical pattern of the frontal sinus and recess cells, the extent of surgery can be planned. This document presents a classification of the extent of surgery based on the anatomical classification. PMID- 26991924 TI - Tumour-Associated Autoantibodies as Diagnostic Biomarkers for Breast Cancer: A Systematic Review and Meta-Analysis. AB - Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour-associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour-associated autoantibody was included in a meta analysis, and its clinical value was determined using Fagan's nomogram. The analysis included 84 studies regarding tumour-associated autoantibodies with the diagnostic value. Anti-p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour-associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti-p53 antibody was included in a meta-analysis. When it had been detected using ELISA and cut-off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagan's nomogram showed post-test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour-associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour-associated autoantibodies as biomarkers for BC detection, a high-quality prospective study is needed to validate their diagnostic value in practice. PMID- 26991923 TI - Body shape, adiposity index, and mortality in postmenopausal women: Findings from the Women's Health Initiative. AB - OBJECTIVE: Studies evaluating the relationship between body mass index (BMI) and mortality demonstrate a U-shaped association. To expand, this study evaluated the relationship between adiposity indices, a body shape index (ABSI) and body adiposity index (BAI), and mortality in 77,505 postmenopausal women. METHODS: A prospective cohort analysis was conducted in the Women's Health Initiative to ascertain the independent relationships between adiposity indices and mortality in order to inform on the clinical usefulness of alternate measures of mortality risk. ABSI (waist circumference (cm)/[BMI(2/3) * height (cm)(1/2) ]), BAI (hip circumference (cm)/[height (m)(1.5) ] - 18), weight, BMI, and waist circumference (WC) were evaluated in relation to mortality risk using adjusted Cox proportional hazards regression models. RESULTS: ABSI showed a linear association with mortality (HR, 1.37; 95% CI, 1.28-1.47 for quintile 5 vs. 1) while BMI and BAI had U-shaped relationships with HR of 1.30; 95% CI, 1.20-1.40 for obesity II/III BMI and 1.06, 95% CI, 0.99-1.13 for BAI. Higher WC (HR, 1.21; 95% CI, 1.13-1.29 for quintile 5 vs. 1) showed relationships similar to BMI. CONCLUSIONS: ABSI appears to be a clinically useful measure for estimating mortality risk, perhaps more so than BAI and BMI in postmenopausal women. PMID- 26991925 TI - Characterization and complete genome sequence analysis of two Myoviral bacteriophages infecting clinical carbapenem-resistant Acinetobacter baumannii isolates. AB - AIMS: The aim of this study was to characterize phenotypical properties, to analyse whole genomes of novel Acinetobacter baumannii phages infecting carbapenem-resistant Ac. baumannii (CRAB) and to evaluate their potential as antimicrobial alternatives to control Ac. baumannii in clinical settings. METHODS AND RESULTS: The Ac. baumannii phages, Betaphi-R1215 and Betaphi-R2315, were isolated from sewage samples. These phages were characterized by transmission electron microscopy, host spectrum, the thermal/pH stability test, the bacterial lysis assay and the whole genome analysis. Both phages lysed 21 of 45 CRAB hosts, and showed high stability at various pH (pH 4-10) and temperature (25-60 degrees C), and were strongly active against host bacteria in vitro. The genomes of Betaphi-R1215 and Betaphi-R2315 are linear double-strands of DNA with 44.866 and 44.846 bp respectively. These two genomes revealed high similarity at the DNA level, but the organization and direction of open reading frames were different. CONCLUSIONS: The Ac. baumannii phages, Betaphi-R1215 and Betaphi-R2315, are novel lytic phages lysing CRAB strains which were isolated from respiratory samples of patients. SIGNIFICANCE AND IMPACT OF THE STUDY: In vitro and in silico data showed that these novel Ac. baumannii phages, Betaphi-R1215 and Betaphi-R2315, have potential as antimicrobial alternatives to control CRAB in healthcare settings. PMID- 26991926 TI - Stable Similariton Generation in an All-Fiber Hybrid Mode-Locked Ring Laser for Frequency Metrology. AB - Ultrashort pulse lasers constitute an important tool in the emerging field of optical frequency metrology and are enabling unprecedented measurement capabilities and new applications in a wide range of fields, including precision spectroscopy, atomic clocks, ultracold gases, and molecular fingerprinting. We demonstrate the generation of stable 127-fs self-similar pulses at a central wavelength of 1560 nm with 7.14-mW average output power. Similariton lasers have a low repetition rate deviation in the averaging time interval [Formula: see text], a low relative intensity noise [Formula: see text] (30 Hz to 10 kHz), a narrow single comb line width of 32 kHz, and high reliability. Thus, such lasers are highly promising for further development of the stabilized combs and open up a robust and substantially simplified route to synthesizing low-noise microwaves. PMID- 26991927 TI - Analysis of lipophilic fluorescent products in blood of Alzheimer's disease patients. AB - Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by cognitive decline. Prodromal stage of AD, also called mild cognitive impairment (MCI), especially its amnestic type (aMCI), precedes dementia stage of AD. There are currently no reliable diagnostic biomarkers of AD in the blood. Alzheimer's disease is accompanied by increased oxidative stress in brain, which leads to oxidative damage and accumulation of free radical reaction end-products. In our study, specific products of lipid peroxidation in the blood of AD patients were studied. Lipophilic extracts of erythrocytes (AD dementia = 19, aMCI = 27, controls = 16) and plasma (AD dementia = 11, aMCI = 17, controls = 16) were analysed by fluorescence spectroscopy. The level of these products is significantly increased in erythrocytes and plasma of AD dementia and aMCI patients versus controls. We concluded that oxidative stress end-products are promising new biomarkers of AD, but further detailed characterisation of these products is needed. PMID- 26991929 TI - A piecewise regression approach for determining biologically relevant hydraulic thresholds for the protection of fishes at river infrastructure. AB - A piecewise regression approach was used to objectively quantify barotrauma injury thresholds in two physoclistous species, Murray cod Maccullochella peelii and silver perch Bidyanus bidyanus, following simulated infrastructure passage in a barometric chamber. The probability of injuries such as swimbladder rupture, exophthalmia and haemorrhage, and emphysema in various organs increased as the ratio between the lowest exposure pressure and the acclimation pressure (ratio of pressure change, R(NE:A) ) reduced. The relationship was typically non-linear and piecewise regression was able to quantify thresholds in R(NE:A) that once exceeded resulted in a substantial increase in barotrauma injury. Thresholds differed among injury types and between species but by applying a multispecies precautionary principle, the maintenance of exposure pressures at river infrastructure above 70% of acclimation pressure (R(NE:A) of 0.7) should protect downstream migrating juveniles of these two physoclistous species sufficiently. These findings have important implications for determining the risk posed by current infrastructures and informing the design and operation of new ones. PMID- 26991928 TI - Production of the Streptomyces scabies coronafacoyl phytotoxins involves a novel biosynthetic pathway with an F420 -dependent oxidoreductase and a short-chain dehydrogenase/reductase. AB - Coronafacoyl phytotoxins are secondary metabolites that are produced by various phytopathogenic bacteria, including several pathovars of the Gram-negative bacterium Pseudomonas syringae as well as the Gram-positive potato scab pathogen Streptomyces scabies. The phytotoxins are composed of the polyketide coronafacic acid (CFA) linked via an amide bond to amino acids or amino acid derivatives, and their biosynthesis involves the cfa and cfa-like gene clusters that are found in P. syringae and S. scabies, respectively. The S. scabies cfa-like gene cluster was previously reported to contain several genes that are absent from the P. syringae cfa gene cluster, including one (oxr) encoding a putative F420 dependent oxidoreductase, and another (sdr) encoding a predicted short-chain dehydrogenase/reductase. Using gene deletion analysis, we demonstrated that both oxr and sdr are required for normal production of the S. scabies coronafacoyl phytotoxins, and structural analysis of metabolites that accumulated in the Deltasdr mutant cultures revealed that Sdr is directly involved in the biosynthesis of the CFA moiety. Our results suggest that S. scabies and P. syringae use distinct biosynthetic pathways for producing coronafacoyl phytotoxins, which are important mediators of host-pathogen interactions in various plant pathosystems. PMID- 26991930 TI - An Apoptosis-Inducing Peptidic Heptad That Efficiently Clusters Death Receptor 5. AB - Multivalent ligands of death receptors hold particular promise as tumor cell specific therapeutic agents because they induce an apoptotic cascade in cancerous cells. Herein, we present a modular approach to generate death receptor 5 (DR5) binding constructs comprising multiple copies of DR5 targeting peptide (DR5TP) covalently bound to biomolecular scaffolds of peptidic nature. This strategy allows for efficient oligomerization of synthetic DR5TP-derived peptides in different spatial orientations using a set of enzyme-promoted conjugations or recombinant production. Heptameric constructs based on a short (60-75 residues) scaffold of a C-terminal oligomerization domain of human C4b binding protein showed remarkable proapoptotic activity (EC50=3 nm) when DR5TP was ligated to its carboxy terminus. Our data support the notion that inter-ligand distance, relative spatial orientation and copy number of receptor-binding modules are key prerequisites for receptor activation and cell killing. PMID- 26991931 TI - Emergence and dissemination of clade 2.3.4.4 H5Nx influenza viruses-how is the Asian HPAI H5 lineage maintained. AB - Highly pathogenic avian influenza (HPAI) A(H5N1) viruses containing the A/goose/Guangdong/96-like (GD/96) HA genes circulated in birds from four continents in the course of 2015 (Jan to Sept). A new HA clade, termed 2.3.4.4, emerged around 2010-2011 in China and revealed a novel propensity to reassort with NA subtypes other than N1, unlike dozens of earlier clades. Two subtypes, H5N6 and H5N8, have spread to countries in Asia (H5N6), Europe and North America (H5N8). Infections by clade 2.3.4.4 viruses are characterized by low virulence in poultry and some wild birds, contributing to wide geographical dissemination of the viruses via poultry trade and wild bird migration. PMID- 26991932 TI - Central administrations of hemopressin and related peptides inhibit gastrointestinal motility in mice. AB - BACKGROUND: Hemopressin was identified as an endogenous inverse agonist/antagonist of CB1 receptor, whereas VD-hemopressin(alpha) [VD-Hpalpha] and VD-hemopressin(beta) [VD-Hpbeta] were found as the novel endogenous peptidic agonists of cannabinoid receptors. As cannabinoids are potent modulators of gastrointestinal (GI) motility, our aim was to characterize the effects of hemopressin and related peptides on GI motility in vivo. METHODS: The responses of intracerebroventricular (i.c.v.) administration of the reference compound WIN55,212-2, hemopressin, and related peptides to GI motility were investigated by measuring upper GI transit, colonic bead expulsion, and whole gut transit in mice. KEY RESULTS: Central administration of the classical cannabinoid receptor agonist WIN55,212-2 dose-dependently slowed upper GI transit, colonic expulsion, and whole gut transit via CB1 receptor. Similarly, Hpalpha, VD-Hpalpha, and VD Hpbeta delayed upper GI transit and colonic expulsion after i.c.v. administration. At the high doses, Hpalpha and VD-Hpbeta inhibited whole gut transit, whereas VD-Hpalpha had no effect on whole gut transit. In addition, the effects of these three peptides on GI transit were antagonized by the CB1 receptor selective antagonist AM251, but not by the CB2 receptor selective antagonist AM630. CONCLUSION & INFERENCES: The endogenous cannabinoid peptide ligands hemopressin, VD-Hpalpha, and VD-Hpbeta inhibited GI transit through the activation of CB1 , but not CB2 cannabinoid receptors. The lower potencies of the hemopressin and related peptides in GI transit assays may be important for the future development of cannabinoid peptides as the therapeutic analgesics with limited GI side effects. PMID- 26991933 TI - Density and Shape Effects in the Acoustic Propulsion of Bimetallic Nanorod Motors. AB - Bimetallic nanorods are propelled without chemical fuels in megahertz (MHz) acoustic fields, and exhibit similar behaviors to single-metal rods, including autonomous axial propulsion and organization into spinning chains. Shape asymmetry determines the direction of axial movement of bimetallic rods when there is a small difference in density between the two metals. Movement toward the concave end of these rods is inconsistent with a scattering mechanism that we proposed earlier for acoustic propulsion, but is consistent with an acoustic streaming model developed more recently by Nadal and Lauga ( Phys. Fluids 2014 , 26 , 082001 ). Longer rods were slower at constant power, and their speed was proportional to the square of the power density, in agreement with the acoustic streaming model. The streaming model was further supported by a correlation between the disassembly of spinning chains of rods and a sharp decrease in the axial speed of autonomously moving motors within the levitation plane of the cylindrical acoustic cell. However, with bimetallic rods containing metals of different densities, a consistent polarity of motion was observed with the lighter metal end leading. Speed comparisons between single-metal rods of different densities showed that those of lower density are propelled faster. So far, these density effects are not explained in the streaming model. The directionality of bimetallic rods in acoustic fields is intriguing and offers some new possibilities for designing motors in which shape, material, and chemical asymmetry might be combined for enhanced functionality. PMID- 26991934 TI - Quality of Community-Based Osteoarthritis Care: A Systematic Review and Meta Analysis. AB - OBJECTIVE: To evaluate the state of quality of care for osteoarthritis (OA) by summarizing studies that have assessed the care provided to patients. METHODS: A systematic review of community-based observational studies of actual clinical practice treating people with OA compared with quality indicators (QIs) was performed. Four databases were searched from January 2000 to November 2015. Two reviewers independently determined study eligibility, assessed risk of bias, and extracted study data. The outcome was adherence to the QIs (pass rate). The overall pass rate (the total number of indicators passed divided by the total number of indicators for which the patients were eligible) was extracted from each study. When at least 50% of the studies had comparable individual QIs, the data were pooled with proportion meta-analyses. RESULTS: Fifteen studies comprising 16,103 patients were included, and the median overall pass rate across studies was 41% (range 22-65%). The pooled pass rates for individual QIs were "referral to orthopedic surgeon if no response to other therapy": 59.4% (95% confidence interval [95% CI] 47.5-70.3); "paracetamol or acetaminophen first drug used": 46.0% (95% CI 26.6-66.7); "assessed for pain and/or function": 45.5% (95% CI 33.9-57.6); "referral or recommendation to exercise": 38.7% (28.9-49.5); "offered education and self-management": 35.4% (95% CI 27.8-44.0); and "informed about potential risks if NSAIDs prescribed": 34.1% (95% CI 24.7-44.9). CONCLUSION: There is room for improvement in community-based OA care. PMID- 26991935 TI - Loss of collapsin response mediator protein 4 suppresses dopaminergic neuron death in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several lines of evidence suggest that neurodegeneration in PD is accelerated by a vicious cycle in which apoptosis in dopaminergic neurons triggers the activation of microglia and harmful inflammatory processes that further amplify neuronal death. Recently, we demonstrated that the deletion of collapsin response mediator protein 4 (CRMP4) suppresses inflammatory responses and cell death in a mouse model of spinal cord injury, leading to improved functional recovery. We thus hypothesized that Crmp4 /- mice may have limited inflammatory responses and a decrease in the loss of SNc dopaminergic neurons in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model. We observed CRMP4 expression in neurons, astrocytes, and microglia/macrophages following the injection of 25 mg/kg MPTP. We compared the number of dopaminergic neurons and the inflammatory response in SNc between Crmp4+/+ and Crmp4-/- mice after MPTP injection. Limited loss of SNc dopaminergic neurons and decreased activations of microglia and astrocytes were observed in Crmp4-/- mice. These results suggest that CRMP4 is a novel therapeutic target in the treatment of PD patients. We demonstrated that genetic CRMP4 deletion delays a vicious cycle of inflammation and neurodegeneration in a Parkinson's disease mouse model. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) injection to wild-type mice induces collapsin response mediator protein 4 (CRMP4) up regulation in neurons, astrocytes, and microglia. CRMP4-deficient mice show reduced inflammation and suppressed dopaminergic neuronal death after MPTP injection. These findings suggest that CRMP4 deletion may be a new therapeutic strategy against Parkinson's diseases. PMID- 26991936 TI - Grade of soluble inflammatory response is mainly affected by circulating bacterial DNA concentrations in cirrhosis. AB - BACKGROUND & AIMS: Patients with decompensated cirrhosis show a marked innate immune response that shows a wide variability. The reasons for this fact have not been previously evaluated. This investigation was undertaken to study factors influencing the immune response intensity in both serum and ascitic fluid in patients with cirrhosis and ascites with presence of bactDNA. METHODS: 77 patients with cirrhosis and presence of bactDNA fragments in blood and ascitic fluid were included. Identification of bactDNA was evaluated by 16SrRNA gene PCR followed by nucleotide sequencing and by species-specific PCR. Concentration of amplified bacterial-DNA, bacteria identification, LPS, TNF-alpha, IFN-gamma, Interleukin 12 and nitric oxide in serum and ascitic fluid were evaluated as factors related to intensity of the immune response. RESULTS: Serum and AF levels of bactDNA, TNF-alpha, IFN-gamma and nitric oxide concentration were higher in patients with presence of bactDNA from gram negative bacteria. Serum TNF-alpha levels showed a significant correlation with concentrations of bactDNA (r = 0.88; P = 0.001) and LPS (r = 0.28; P = 0.016). Serum nitric oxide levels were also significantly correlated with concentrations of bactDNA (r = 0.761; P = 0.001) but not with LPS levels. Levels of INF-gamma and IL-12 were not significantly correlated with either bactDNA nor LPS levels. Plasmatic concentration of bactDNA was the most accurately correlated factor with the inflammatory response (ancova model included only levels of bactDNA (r(2) = 0.87, P = 0.047 for TNF-alpha; r(2) = 0.45, P = 0.03 for NOx). CONCLUSIONS: Bacterial-DNA concentration is the most influencing variable associated with serum TNF-alpha and nitric oxide response. PMID- 26991937 TI - Stomatognathic function in Duchenne muscular dystrophy: a case-control study. AB - AIM: This study aimed to analyse electromyographic activity, masticatory efficiency, muscle thickness, and bite force of individuals with Duchenne muscular dystrophy (DMD). METHOD: Forty males aged 4-15 years, 20 with DMD and 20 healthy age-, height-, and weight-matched controls, underwent electromyography and ultrasonography of temporalis, masseter, and sternocleidomastoid muscles during postural control of the jaw, mastication, and maximal molar bite force. RESULTS: The normalized electromyography signals showed higher activity in masseter and temporal muscles at rest, during protrusion, left and right laterality, and fatigue condition in the group with DMD than in the comparison group (p<=0.05). For masticatory efficiency of cycles, in analysis of non habitual chewing of flavourless gum, and habitual chewing of peanuts and raisins, the group with DMD presented lower averages (p<=0.05). For the muscle thickness, the results showed that there was a lower muscle thickness in the group with DMD for all muscles during the rest and maximal voluntary contraction, except for masseter and sternocleidomastoid in the maximal voluntary contraction. In the maximal molar bite force, the group with DMD presented higher values for both sides than the comparison group (p<=0.05). INTERPRETATION: Patients with DMD show muscle changes related to the stomatognathic system, in their activity, bite force, and muscle thickness. PMID- 26991938 TI - Discovery of novel diaryl urea derivatives bearing a triazole moiety as potential antitumor agents. AB - Herein, we report a novel series of diaryl urea derivatives bearing a triazole moiety, from which potent antitumor agents have been identified. With a modified triazole, most compounds showed high level activity in both cellular and enzymatic assays, accompanied with a suitable ClogD7.4 value. The most active compound, 13i, effectively suppressed proliferation of HT-29, H460 and MDA-MB-231 cancer cells, with IC50 values of 0.90, 0.85 and 1.54 MUM, respectively. Compound 13i also exhibited significant inhibition of tyrosine kinases including c-Kit, RET and FLT3. Furthermore, compound 13i could obviously induce apoptosis of HT-29 cells in a concentration-dependent manner. The study of structure-activity relationships also revealed that a hydrophilic tail at the 4-position of the triazole was crucial for high activity of the compound. PMID- 26991940 TI - Correction: Cannibalism, Kuru, and Mad Cows: Prion Disease As a "Choose-Your-Own Experiment" Case Study to Simulate Scientific Inquiry in Large Lectures. PMID- 26991939 TI - 2,8-Diazaspiro[4.5]decan-8-yl)pyrimidin-4-amine potent CCR4 antagonists capable of inducing receptor endocytosis. AB - A number of potent 2,8-diazaspiro[4.5]decan-8-yl)pyrimidin-4-amine CCR4 antagonists binding to the extracellular allosteric site were synthesised. (R)-N (2,4-Dichlorobenzyl)-2-(2-(pyrrolidin-2-ylmethyl)-2,8-diazaspiro[4.5]decan-8 yl)pyrimidin-4-amine (R)-(18a) has high affinity in both the [(125)I]-TARC binding assay with a pKi of 8.8, and the [(35)S]-GTPgammaS functional assay with a pIC50 of 8.1, and high activity in the human whole blood actin polymerisation assay (pA2 = 6.7). The most potent antagonists were also investigated for their ability to induce endocytosis of CCR4 and were found to internalise about 60% of the cell surface receptors, a property which is not commonly shared by small molecule antagonists of chemokine receptors. PMID- 26991941 TI - Polyfunctional Lithium, Magnesium, and Zinc Alkenyl Reagents as Building Blocks for the Synthesis of Complex Heterocycles. AB - New conjunctive beta-silylated organometallic reagents of Li, Mg, and Zn have been prepared and used for an expeditive construction of various polyfunctionalized 5-, 6-, and 7-membered heterocycles, such as furans, pyrroles, quinolines, benzo[b]thieno-[2,3-b]pyridine, naphthyridines, fused pyrazoles, and 2,3-dihydro-benzo[c]azepines. The latent silyl group has been converted into various carbon-carbon bonds in most heterocycle types. PMID- 26991942 TI - Women and Health: Women's Dual Roles as Both Recipients and Providers of Healthcare. AB - With the many economic, demographic, social and epidemiological global transitions, a Harvard-Penn-Lancet commission reviewed the current health status of women and its relationship to sustainability, and redefined the field as women and health. Four major recommendations were offered, insuring mechanisms to count women properly as providers and recipients of care, to value them by insuring protective policies, to treat and compensate them fairly and equitably, and to develop strategies to be accountable for sustaining and implementing the recommendations. However, without a life span approach to women, and their health, and without universal access to comprehensive health care, women's wellbeing and abilities to function up to their full capacities will be compromised. These recommendations have many implications for health care, education and practice. PMID- 26991943 TI - Solute Migration from the Aquifer Matrix into a Solution Conduit and the Reverse. AB - : A solution conduit has a permeable wall allowing for water exchange and solute transfer between the conduit and its surrounding aquifer matrix. In this paper, we use Laplace Transform to solve a one-dimensional equation constructed using the Euler approach to describe advective transport of solute in a conduit, a production-value problem. Both nonuniform cross-section of the conduit and nonuniform seepage at the conduit wall are considered in the solution. Physical analysis using the Lagrangian approach and a lumping method is performed to verify the solution. Two-way transfer between conduit water and matrix water is also investigated by using the solution for the production-value problem as a first-order approximation. The approximate solution agrees well with the exact solution if dimensionless travel time in the conduit is an order of magnitude smaller than unity. Our analytical solution is based on the assumption that the spatial and/or temporal heterogeneity in the wall solute flux is the dominant factor in the spreading of spring-breakthrough curves, and conduit dispersion is only a secondary mechanism. Such an approach can lead to the better understanding of water exchange and solute transfer between conduits and aquifer matrix. HIGHLIGHTS: Euler and Lagrangian approaches are used to solve transport in conduit. Two-way transfer between conduit and matrix is investigated. The solution is applicable to transport in conduit of persisting solute from matrix. PMID- 26991944 TI - A systematic literature review on nurses' and health care support workers' experiences of caring for people with dementia on orthopaedic wards. AB - AIMS AND OBJECTIVES: To review literature on nurses' and health care workers' experiences of caring for people with dementia on orthopaedic wards. BACKGROUND: Dementia is a condition that affects a large number of the older population worldwide. It is estimated that there are 47.5 million people worldwide living with dementia with 4.6 million new cases being diagnosed annually. This number is said to increase to 75.6 million by 2030 and triple by 2050. It is also acknowledged that older people are at a greater risk of falls that are a devastating problem causing a tremendous amount of morbidity, mortality and use of health care services (Rubestein, Age and Ageing, 35, 2006, 37). Falls usually result from identified risk factors such as weakness, unsteady gait, confusion and certain medication. Therefore, it is reasonable to assume that a large population of older people suffering from dementia may be admitted to orthopaedic wards with various injuries. Nurse and support health workers may experience a range of difficulties when caring for this population of patients. DESIGN: A systematic review. METHODS: An extensive literature search using; CINAHL, MEDLINE, Academic Search Complete, National Health Service Evidence, websites like Department of Health, Dementia and Alzheimer's Society. RESULTS: The search generated several articles on dementia in general, however, only 14 articles dealing with care of these people in an acute hospital setting were found. No studies dealing with the care of people with dementia on orthopaedic wards were found; therefore, this review has taken a generalist nature and applies the findings to orthopaedic wards. The main themes identified from the review were: challenging behaviour and unsuitable care environment; lack of education on dementia; strain from nursing patients with dementia; and ethical dilemmas arising from care of people with dementia. CONCLUSION: It would be an over simplification to say that the care of people with dementia on medical wards is the same as the care of trauma patients with dementia. Therefore, there is a need for a study to explore nurses' and health care worker's experiences of caring for trauma patients with dementia on orthopaedic wards. RELEVANCE TO CLINICAL PRACTICE: The results of this study could provide guidance on the effective care of people with dementia on orthopaedic wards. PMID- 26991945 TI - Multiple Subsets of Brain Tumor Initiating Cells Coexist in Glioblastoma. AB - Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs coexisting in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to divergent bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. Stem Cells 2016;34:1702-1707. PMID- 26991946 TI - Dying Care Nursing Intervention in the Institutional Care of End-of-Life Patients. AB - PURPOSE: To determine the frequency of the Nursing Intervention Classification Dying Care activities performed by nurses with end-of-life (EOL) patients. METHODS: A cross-sectional, descriptive study using a structured questionnaire to determine the frequencies of Dying Care activities performed by 201 Czech nurses. FINDINGS: Nurses reported more frequent use of activities focused on the physical comfort of EOL patients. Significant relationships were found between frequencies in some activities and the nurses' education level, length of work experience, and the department type. CONCLUSIONS: Nurses reported infrequent use of communication activities with patients and relatives, which is related to the length of practice. CLINICAL RELEVANCE: It is necessary to focus on communication and psychosocial needs of EOL patients in both pregradual and lifelong nursing education. CIL: Zjistit frekvenci aktivit NIC intervence Pece o umirajici mezi ceskymi sestry u pacientu v zaveru zivota. METODY: Prurezova deskriptivni studie vyuzivajici strukturovaneho dotazniku pro urceni frekvence aktivit Pece o umirajici provadene 201 sestrou. VYSLEDKY: Sestry u pacientu v zaveru zivota castejsi vyuzivaji aktivity zamerene na fyzicky komfort. Vyznamne vztahy byly nalezeny mezi frekvenci nekterych aktivit a urovni vzdelani sester, delkou praxe a typem pracoviste. ZAVERY: Sestry uvadely neprilis caste pouzivani komunikacnich aktivit s pacienty a pribuznymi, coz souvisi s delkou jejich praxe. KLINICKA RELEVANCE: Je treba se zamerit na komunikaci a psychosocialni potreby pacientu v zaveru zivota jak v pregradualnim tak celozivotnim vzdelavani sester. PMID- 26991947 TI - Expanding marine protected areas to include degraded coral reefs. AB - Marine protected areas (MPAs) are a commonly applied solution to coral reef degradation, yet coral reefs continue to decline worldwide. We argue that expanding the range of MPAs to include degraded reefs (DR-MPA) could help reverse this trend. This approach requires new ecological criteria for MPA design, siting, and management. Rather than focusing solely on preserving healthy reefs, our approach focuses on the potential for biodiversity recovery and renewal of ecosystem services. The new criteria would help identify sites with the highest potential for recovery and the greatest resistance to future threats (e.g., increased temperature and acidification) and sites that contribute to MPA connectivity. The DR-MPA approach is a compliment rather than a substitute for traditional MPA design approaches. We believe that the DR-MPA approach can enhance the natural, or restoration-assisted, recovery of DRs and their ecosystem services; increase total reef area available for protection; promote more resilient and better-connected MPA networks; and improve conditions for human communities dependent on MPA ecosystem services. PMID- 26991948 TI - Green tea polyphenol epigallocatechin-3-gallate improves epithelial barrier function by inducing the production of antimicrobial peptide pBD-1 and pBD-2 in monolayers of porcine intestinal epithelial IPEC-J2 cells. AB - SCOPE: Green tea has been known to confer numerous health benefits such as the prevention of cardiovascular disease, cancers, and obesity. Epigallocatechin-3 gallate (EGCG) is the major polyphenol present in green tea. Since EGCG is a food derived component, intestinal epithelial cells lining the gastrointestinal tract are constantly and directly exposed to EGCG. It is anticipated that EGCG can exert beneficial effects in the intestine. The aim of this study was to explore the protective effects of EGCG on intestinal barrier functions against bacterial translocation by using a porcine jejunal epithelial cell line, IPEC-J2. METHODS AND RESULTS: EGCG reduced bacterial translocation across IPEC-J2 cell monolayers through the enhancement of the intestinal epithelial immunological barrier function by inducing secretion of antimicrobial peptides, porcine beta-defensins 1 and 2 (pBD-1 and 2), which possessed higher antimicrobial activity against Escherichia coli. Further mechanistic studies demonstrated that EGCG upregulated pBD-2 but not pBD-1 via the p38 mitogen-activated protein kinase dependent pathway. Such effects were not an "artifact" of hydrogen peroxide, catechin dimers, or other auto-oxidation products generated from EGCG in cell culture media. CONCLUSION: Our results imply that EGCG may be useful for prevention of intestinal disorders or bacterial infection in animals/humans. PMID- 26991949 TI - Dislocation of a dual mobility total hip replacement following fracture of the polyethylene liner. AB - An eight-year-old male English Setter was referred for management of a dislocation of a cemented dual mobility canine total hip prosthesis that occurred four months after the initial surgery. Revision surgery showed that the dislocation was associated with fracture of the ultra-high molecular weight polyethylene liner. The dislocation was successfully reduced after replacing the liner. A dual mobility acetabular component is composed of a mobile polyethylene liner inside a metallic cemented cup. Chronic wear of the components of a canine dual mobility total hip replacement has not been described previously. The use of this type of implant is fairly recent and limited long term follow-up of the implanted cases may be the explanation. Acute rupture of a polyethylene liner has never been described in humans, the only case of rupture of a polyethylene liner occurred 10 years after implantation. The case presented here of rupture of the polyethylene liner of a dual mobility total hip replacement is a hitherto unreported failure mode in this model of acetabular cup in the dog. PMID- 26991950 TI - The East African Training Initiative. A Model Training Program in Pulmonary and Critical Care Medicine for Low-Income Countries. AB - Despite an extensive burden of lung disease in East Africa, there are remarkably few pulmonary physicians in the region and no pulmonary subspecialty training programs. We developed a unique training program for pulmonary medicine in Ethiopia. The East African Training Initiative (EATI) is a 2-year fellowship program at Tikur Anbessa (Black Lion) Specialized Teaching Hospital, the largest public hospital in Ethiopia and the teaching hospital for the Addis Ababa University School of Medicine. The first year is devoted to clinical care and procedural skills. Lectures, conferences, daily inpatient and outpatient rounds, and procedure supervision by visiting faculty provide the clinical knowledge foundation. In the second year, training in clinical research is added to ongoing clinical training. Before graduation, fellows must pass rigorous written and oral examinations and achieve high marks on faculty evaluations. Funding derives from several sources. Ethiopian trainees are paid by the Ethiopian Ministry of Health and the Addis Ababa University School of Medicine. The World Lung Foundation and the Swiss Lung Foundation supply travel and housing costs for visiting faculty, who receive no other stipend. The first two trainees graduated in January 2015, and a second class of three fellows completed training in January 2016. All five presented research abstracts at the annual meetings of the International Union Against Tuberculosis and Lung Disease in 2014 and 2015. The EATI has successfully provided pulmonary medicine training in Ethiopia and has capacity for local leadership. We believe that EATI could be a model for other resource-limited countries. PMID- 26991951 TI - Greatly Enhanced Fluorescence by Increasing the Structural Rigidity of an Imine: Enantioselective Recognition of 1,2-Cyclohexanediamine by a Chiral Aldehyde. AB - An aldehyde that is not fluorescent responsive toward a chiral diamine has been converted to a sensitive fluorescence enhancement sensor through incorporation of an additional hydrogen bonding unit to increase the structural rigidity of the reaction product of the aldehyde with the diamine. This new chiral aldehyde is synthesized in one step from the reaction of (S)-3-formylBINOL with salicyl chloride. When treated with trans-1,2-cyclohexanediamine in ethanol, it shows greatly enhanced fluorescence at lambda=410 nm with good enantioselectivity. NMR and mass spectroscopic methods are used to investigate the reaction of the chiral aldehyde with the diamine. This study has revealed a two-stage reaction mechanism including a fast imine formation and a slow ester cleavage. PMID- 26991952 TI - Recent developments in identifying and quantifying emotions during food consumption. AB - Emotions and the consumption of food and beverages are inextricably intertwined. As the fields of sensory and consumer science seek to better conceptualize the consumer experience, interest in emotion measurement is growing. Emotions can provide key information to differentiate between products and predict consumer choice as well as give more detail about product perception. There are several emotion measurement instruments, including physiological methods and facial recognition, self-reported verbal emotion measurement and self-reported visual emotion measurement. This review discusses the purpose of measuring emotions, what is the definition of an emotion, what different instruments are available, and touches upon some promising research to deepen the connection between food and emotions. (c) 2016 Society of Chemical Industry. PMID- 26991953 TI - Participation in a clinical trial for a child with cancer is burdensome for a minority of children. AB - AIM: This study explored how parents who had lost a child to cancer felt about them taking part in a clinical trial. METHODS: A retrospective questionnaire was sent to parents who had lost a child to cancer. They were asked whether their child took part in a clinical trial during their palliative phase, their motives for their child's participation, how they perceived their child's burden and whether they would, hypothetically speaking, enrol again. RESULTS: The 24 parents of 16 deceased children who had participated in a clinical trial explained their motives for their child's participation. The most common answers, with multiple responses, were treatment for future patients (n = 16), hope for a cure (n = 9) and prolonging their child's life (n = 6). Eight parents said that participating was not burdensome for their child and four said it was very burdensome, with others answering in between. None of the parents would decline participation if they would be in the same situation again. CONCLUSION: Performing clinical trials, even in a vulnerable population, such as children with cancer at the end of life, may not always lead to increased burden. None of the parents would in future, given the same circumstances, decline participation in a clinical trial. PMID- 26991954 TI - Genetic alteration of UDP-rhamnose metabolism in Botrytis cinerea leads to the accumulation of UDP-KDG that adversely affects development and pathogenicity. AB - Botrytis cinerea is a model plant-pathogenic fungus that causes grey mould and rot diseases in a wide range of agriculturally important crops. A previous study has identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of uridine diphosphate (UDP)-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolishes the production of rhamnose containing glycans in these mutant strains. Deletion of bcdh or double deletion of both bcdh and bcer has no apparent effect on fungal development or pathogenicity. Interestingly, deletion of the bcer gene alone adversely affects fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production and virulence. Treatments with wall stressors suggest the alteration of cell wall integrity. Analysis of nucleotide sugars reveals the accumulation of the UDP-rhamnose pathway intermediate UDP-4 keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Deltabcer strain. UDP-KDG could not be detected in hyphae of the wild-type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. The correlation between high UDP-KDG and modified cell wall and developmental defects raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition, and hence on virulence. This is the first report demonstrating that the accumulation of a minor nucleotide sugar intermediate has such a profound and adverse effect on a fungus. The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG may lead to the development of new antifungal drugs. PMID- 26991955 TI - E-Cadherin Facilitates Protein Kinase D1 Activation and Subcellular Localization. AB - Protein kinase D 1 (PKD1) is a serine/threonine kinase implicated in the regulation of diverse cellular functions including cell growth, differentiation, adhesion and motility. The current model for PKD1 activation involves diacylglycerol (DAG) binding to the C1 domain of PKD1 which results in the translocation of PKD1 to subcellular membranes where PKD1 is phosphorylated and activated by protein kinase C (PKC). In this study, we have identified a novel regulation of PKD1 activation. The epithelial cell membrane protein E-cadherin physically binds to PKD1 which leads to a subcellular redistribution of PKD1. Furthermore, artificial targeting of PKD1 to the membrane leads to PKD1 activation in a PKC-independent manner, indicating that membrane attachment is sufficient enough to activate PKD1. The presence of E-cadherin dynamically regulates PKD1 activation by Bryostatin 1, a potent activator of PKD1, and its substrate phosphorylation specificity, implying a loss of E-cadherin during cancer metastasis could cause the re-distribution PKD1 and re-wiring of PKD1 signaling for distinct functions. The knocking down of PKD1 in lung epithelial cell line A549 results in an epithelial to mesenchymal transition with changes in biomarker expression, cell migration and drug resistance. These results extend our previous understanding of PKD1 regulation and E-cadherin signaling functions and may help to explain the diversified functions of PKD1 in various cells. J. Cell. Physiol. 231: 2741-2748, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991956 TI - Subtype-specific incidence rates of lymphoid malignancies in Hong Kong compared to the United States, 2001-2010. AB - Clinical studies of lymphoid malignancies (LMs) have suggested that the descriptive patterns of LMs differ in East Asia compared to Western populations. However, there are very limited available data on population-based, subtype specific incidence rates of LMs in the East Asian population, particularly in Chinese. Using data from the Hong Kong (HK) Cancer Registry and United States (U.S.) SEER Program, we calculated and compared age-adjusted incidence rates of LM subtypes in HK to those in Whites and Asians living in the U.S. Overall and sex-specific rates were calculated for the period 2001-2010. The incidence of most subtypes was low in the HK population, with rates <1 case per 100,000 for all subtypes except for diffuse large B-cell lymphoma (3.26/100,000) and plasma cell neoplasms (1.99/100,000). Age-adjusted incidence rates of all evaluated B cell subtypes were significantly higher in U.S. Whites compared to HK, with standardized rate ratios (SRRs) ranging from 1.6 (Burkitt lymphoma) to 9.1 (chronic lymphocytic leukemia/small lymphocytic lymphoma). Rates in U.S. Asians were generally intermediate to those in U.S. Whites and HK. Conversely, rates of extranodal NK/T-cell lymphoma were significantly lower in both U.S. Whites (SRR=0.2) and U.S. Asians (SRR=0.5) compared to HK. Our data provide new insight into the subtype-specific patterns of LMs in the Chinese population, and suggest the need for etiological studies of LMs in the East Asian population to elucidate the factors responsible for these differences in the geographic incidence patterns. PMID- 26991957 TI - Prevalence of anal incontinence during pregnancy and 1 year after delivery in a cohort of primiparous women and a control group of nulliparous women. AB - INTRODUCTION: The aim of the study was to examine the prevalence of anal incontinence (AI) during pregnancy and 1 year after delivery in primiparous women and to compare it with the prevalences in nulliparous women. MATERIAL AND METHODS: A validated questionnaire regarding AI was filled in by 1018 primiparous women after delivery and by 1836 nulliparous women (baseline). A similar questionnaire was filled in 1 year later by both groups. RESULTS: At baseline the prevalence of flatus incontinence was significantly higher in the primiparous than the nulliparous women (35 vs. 25%), while incontinence for liquid stools was significantly less frequent (8 vs. 20%). Prevalences of incontinence for solid stools were similar. One year later the prevalence of AI was similar in the two groups (flatus incontinence 24 vs. 25%, incontinence for liquid stools 18 vs. 19% and incontinence for solid stools 4 vs. 3%). AI 1 year after the delivery was not related to the mode of delivery. Women with grade 3 or 4 perineal lesions had a significantly higher prevalence of flatus incontinence 1 year after the delivery compared with women without such lesions (48 vs. 23%, p = 0.00). CONCLUSIONS: This prospective cohort study showed remarkably high prevalences of AI during pregnancy and 1 year after delivery in primiparous women and likewise in nulliparous women at baseline and 1 year later. These results may indicate that factors other than pregnancy and delivery are of importance for AI in young women. PMID- 26991958 TI - Double-dorsal versus single-volar digital subcutaneous anaesthetic injection for finger injuries in the emergency department: A randomised controlled trial. AB - OBJECTIVE: The objective of this present study is to compare pain associated with the double-dorsal versus a single-volar subcutaneous injection in the provision of digital anaesthesia for finger injuries presenting to the ED. METHODS: A randomised controlled trial from November 2012 to January 2014 at a single adult tertiary-referral hospital. ED patients with finger injuries requiring digital anaesthesia was randomised to either the double-dorsal or a single-volar subcutaneous injection technique. The primary outcome was patient reported injection pain measured on a 100 mm visual analogue scale with the assessor blinded to the injection technique. The secondary outcome was success of anaesthesia defined as ability to perform the assessment and treatment without further anaesthetic supplementation after 5 min. RESULTS: Eighty-six patients were enrolled. Median (IQR) age was 34 (24-47) years and 79% were men. The majority (66.3%) had distal phalanx injuries. Forty patients were randomised to the double-dorsal and 46 to a single-volar subcutaneous injection technique. The mean (standard deviation) pain score of the double-dorsal injection was 39.1 (24.2) and a single-volar injection was 37.3 (24.5) with a difference of 1.8 (95% CI -8.8 to 12.3). Digital anaesthesia was successful in 64.9% of the double dorsal and 71.7% of the single-volar subcutaneous injections, a difference of 6.8% (95% CI -12.7 to 26.3). CONCLUSION: In ED patients with finger injuries requiring digital anaesthesia, both the double-dorsal or single-volar subcutaneous injection techniques have similar pain of injection and success rates of anaesthesia. Single-volar injection appears suitable alternative to the commonly performed double-dorsal injection in the ED. PMID- 26991959 TI - Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma. AB - This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0.001, hazard ratio (HR) 2.42, multivariate P = 0.02, HR 2.7) and exchange rate constant kep (univariate P = 0.03, HR 1.92, multivariate P = 0.46, HR 1.5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0.89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS. PMID- 26991960 TI - Synthesis of Graphene Films on Copper Foils by Chemical Vapor Deposition. AB - Over the past decade, graphene has advanced rapidly as one of the most promising materials changing human life. Development of production-worthy synthetic methodologies for the preparation of various types of graphene forms the basis for its investigation and applications. Graphene can be used in the forms of either microflake powders or large-area thin films. Graphene powders are prepared by the exfoliation of graphite or the reduction of graphene oxide, while graphene films are prepared predominantly by chemical vapor deposition (CVD) on a variety of substrates. Both metal and dielectric substrates have been explored; while dielectric substrates are preferred over any other substrate, much higher quality graphene large-area films have been grown on metal substrates such as Cu. The focus here is on the progress of graphene synthesis on Cu foils by CVD, including various CVD techniques, graphene growth mechanisms and kinetics, strategies for synthesizing large-area graphene single crystals, graphene transfer techniques, and, finally, challenges and prospects are discussed. PMID- 26991961 TI - Bronsted Acid Catalyzed [3+2]-Cycloaddition of 2-Vinylindoles with In Situ Generated 2-Methide-2H-indoles: Highly Enantioselective Synthesis of Pyrrolo[1,2 a]indoles. AB - Pyrrolo[1,2-a]indoles are privileged structural elements of many natural products and pharmaceuticals. An efficient one-step process for their highly diastereo- and enantioselective synthesis, comprising a direct [3+2]-cycloaddition, has been developed. A chiral BINOL-derived phosphoric acid catalyzes the reaction of in situ-generated 2-methide-2H-indoles with 2-vinylindoles, furnishing the target products incorporating three contiguous stereogenic centers as single diastereoisomers and with excellent yields and enantioselectivities. PMID- 26991962 TI - Edoxaban: A Novel Factor Xa Inhibitor for the Management of Non-valvular Atrial Fibrillation and Venous Thromboembolism. AB - Warfarin has been a highly prevalent agent for over 70 years; however, its use has been limited by drug-drug interactions, adverse events, and the need for frequent monitoring. To minimize these complications, several non-vitamin K oral anticoagulants have been approved, including the latest agent, edoxaban. Edoxaban is a factor Xa inhibitor approved for the prevention of stroke/systemic embolism in patients with non-valvular atrial fibrillation and for the treatment of venous thromboembolism. Edoxaban was largely studied in the Edoxaban versus Warfarin in Patients with Atrial Fibrillation (ENGAGE AF-TIMI 48) and Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism (Hokusai-VTE) trials, both showing noninferiority when compared with warfarin. Similar to other oral anticoagulants, the most serious adverse effects of edoxaban are related to bleeding. However, there are currently no approved reversal agents. Andexanet alfa and ciraparantag are the latest agents being studied for reversal. This article provides an overview of the safety and efficacy along with the advantages and disadvantages of edoxaban. PMID- 26991963 TI - Preoperative preemptive drug administration for acute postoperative pain: A systematic review and meta-analysis. AB - Preoperative administration of pharmacological substances, such as non-steroidal anti-inflammatory drugs or opioids, has been gaining acclaim as a preemptive measure to minimize postoperative pain. This systematic review and meta-analysis aimed at evaluating the effectiveness of this approach in adults undergoing surgical procedures. MEDLINE, EMBASE and the Cochrane Central Register were searched from inception through January 2015. Data from randomized placebo controlled trials were screened, extracted and assessed for risk of bias according to The Cochrane Collaboration's Tool by two independent authors. The primary outcome measure was reduction in postoperative analgesic consumption during 24 h post surgery; effects were described as mean differences between the drug and placebo arms with corresponding 95% confidence intervals (CIs) and were pooled using random-effects models. Potential publication bias was tested using funnel plots and Egger's regression test for funnel plot asymmetry. Screened were 511 records, of which 39 were included in the final synthesis with data from 3172 patients. A significant reduction in postoperative analgesic consumption was observed using preoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs; 95% CI, -0.61 to -0.14; 31 comparisons), chiefly by the COX-2 inhibitors class (95% CI, -0.95 to -0.33; 13 comparisons). Significant reduction was also observed for gabapentin (95% CI, -1.60 to -0.38; 6 comparisons). No significant effects were observed using opioids, propionic acids or oxicam derivatives. WHAT DOES THIS REVIEW ADD?: Current analyses endorse the effectiveness of COX-2 inhibitors and gabapentin in reducing acute postoperative pain when administered preemptively presurgery. Such corroboration is not found for opioids and other NSAID classes. PMID- 26991964 TI - Monitoring Conformational Changes in the Receptor Tyrosine Kinase EGFR. AB - The receptor tyrosine kinase EGFR is regulated by complex conformational changes, and this conformational control is disturbed in certain types of cancer. Many ligands are known to bind EGFR in its active conformation, thereby preventing ATP from binding. Only a few ligands are known to stabilize EGFR in its inactive conformation, thus providing novel strategies for perturbing EGFR activity. We report a direct binding assay that enables the identification of novel ligands that bind to and stabilize the inactive conformation of EGFR. PMID- 26991966 TI - Rapid determination of trace polycyclic aromatic hydrocarbons in particulate matter using accelerated solvent extraction followed by ultra high performance liquid chromatography with fluorescence detection. AB - A method has been developed for the trace analysis of polycyclic aromatic hydrocarbons, which are known as persistent organic pollutants and ubiquitous constituents of fine particulate matter that causes growing airborne pollution. The method, which was especially for samples of airborne particulate matter less than 2.5 MUm in diameter, utilized accelerated solvent extraction and ultra high performance liquid chromatography with fluorescence detector. Four principal parameters of accelerated solvent extraction were optimized to obtain maximum extraction efficiency. Using the established synergetic programs of gradient elution and fluorescence wavelength switching, a rapid separation was achieved in 6.56 min with good linearity for 15 polycyclic aromatic hydrocarbons (coefficient of determination above 0.999). The limits of detection ranged from 0.833 to 10.0 pg/m(3) . The precision of the method expressed as inter-day relative standard deviation ranged from 0.2 to 1%, which was calculated from nine repetitive measurements of 8.00 MUg/L analytes. Average spiked recoveries ranged from 71.6 to 97.7%, with the exception of naphthalene. The rapid, sensitive, and accurate method can meet the pressing needs of health risk assessment and increasingly heavy daily tasks of air quality monitoring. PMID- 26991965 TI - Early severe scoliosis in a patient with atypical progressive pseudorheumatoid dysplasia (PPD): Identification of two WISP3 mutations, one previously unreported. AB - Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive disorder characterized by spondyloepiphyseal dysplasia associated with pain and stiffness of multiple joints, enlargement of the interphalangeal joints, normal inflammatory parameters, and absence of extra-skeletal manifestations. Homozygous or compound heterozygous WISP3 mutations cause PPD. We report two siblings from a non-consanguineous Ecuadorian family with a late-onset spondyloepiphyseal dysplasia. Mutation screening was undertaken in the two affected siblings using a customized skeletal dysplasia next generation sequencing (NGS) panel and confirmed by Sanger sequencing. Two compound heterozygous mutations were identified in WISP3 exon 2, c.[190G>A];[197G>A] (p.[(Gly64Arg)];[(Ser66Asn)]) in the two siblings, both of which had been inherited. The p. (Gly64Arg) mutation has not been previously described whilst the p. (Ser66Asn) mutation has been reported in two PPD families. The two siblings presented with atypical PPD, as they presented during late childhood, yet the severity was different between them. The progression was particularly aggressive in the male sibling who suffered severe scoliosis by the age of 13 years. This case reaffirms the clinical heterogeneity of this disorder and the clinical utility of NGS to genetically diagnose skeletal dysplasias, enabling adequate management, monitorization, and genetic counseling. (c) 2016 Wiley Periodicals, Inc. PMID- 26991967 TI - The spectrophotometrical analysis of rhododendrol-induced leucoderma using a novel multispectral camera. AB - BACKGROUND: Many users in Japan of skin brightening/lightening cosmetics containing rhododendrol (RD) have developed leucoderma. Leucoderma appears on skin areas repeatedly treated with RD-containing cosmetics. RD-induced leucoderma (RDIL) presents different degrees of well-defined hypopigmentation. It is crucial to determine the degree of hypopigmentation to differentiate RDIL from vitiligo vulgaris (VV). OBJECTIVES: To quantitatively evaluate hypopigmentation of RDIL lesions and the recovery of pigmentation, and to compare the hypopigmentation with VV and normal skin. MATERIALS AND METHODS: Sixteen cases of RDIL, nine cases of VV and 15 healthy controls were examined using a novel multispectral camera (MSC) that can simultaneously obtain the reflection intensity at 10-nm wavelength intervals from 400 to 760 nm of the photographed area. ?Absorbance was calculated by subtracting the log of reflection intensity of the target area from that of a white reflection standard. RESULTS: Most RDIL lesions showed lower ?Absorbance than healthy skin and higher ?Absorbance than VV lesions between 400 and 550 nm. Statistical comparison of the maximum ?Absorbance from 420 to 460 nm (Max?Absorbance) for VV, RDIL and control skin showed that the Max?Absorbance of RDIL was significantly higher than that of VV and lower than that of control skin. The comparison of ?Absorbance of the same sites in RDIL lesions between the initial visit and 6 months later showed significant improvement after 6 months. CONCLUSIONS: These studies demonstrated quantitative changes in RDIL and its recovery phase and suggested the utility of a MSC in obtaining objective colour information of skin disorders. PMID- 26991968 TI - Trimeric and Tetrameric Electron-Deficient Porphyrin Tapes. AB - New hybrid porphyrin tapes comprising meso-3,5-di-tert-butylphenyl-substituted Zn(II) -porphyrins (D) and meso-pentafluorophenyl-substituted Zn(II) -porphyrins (A) were synthesized via cross-condensation of meso-formyl porphyrins 1, 5, and 9 with oligopyrromethanes 2 and 6 as key steps. These hybrid tapes exhibit improved solubilities and enhanced chemical stability as compared with original Dn porphyrin tapes, and all display remarkably coplanar structures favorable for pi conjugation. The absorption spectrum of ADDA displays Q-like bands at 1400 and 1657 nm with a vibronic structure characteristic of porphyrinoids. The cyclic voltammograms exhibited positively shifted oxidation and reduction waves in the order of DDD 0.01). Although there is no significant difference in PV PSV, HA PSV, SMA PSV, SMA EDV values between the groups, mean values of Type II alcoholics is greater than other groups. Portal vein cross-sectional area was greater in alcoholic patients (Type I, II and III) compared to the control group (P = 0.000). Portal vein velocity, hepatic artery peak systolic and end diastolic velocity, superior mesenteric artery peak systolic and end diastolic velocity were significantly greater in alcoholic patients than in the control group (P < 0.001). No statistical difference was detected between other parameters evaluated. CONCLUSION: In alcohol dependent patients, some hemodynamic and morphologic changes occur in hepatic and splanchnic circulation, even before the signs of hepatic damage develop, which can be detected by means of Doppler and gray-scale sonography. But as there is no significant difference between the Doppler ultrasonographic findings among alcoholics subtyped by a Cloninger classification, which is a clinical classification, it suggests that psychiatric classification doesn't show any correlation with biological parameters, and because of this Cloninger classification a psychiatric classification cannot be considered as a characteristic determinative factor in the prognosis of hepatic disorder due to alcohol use. However, higher values of Type II alcoholics can be attributed to the longer alcohol intake of this subtype. PMID- 26991977 TI - Large cava septi pellucidi in schizophrenic patients, alcoholics, head traumatized, and normal individuals: morpholgical features and forensic implications. A postmortem study. AB - BACKGROUND: The enlarged cava septi pellucidi (CSP = 6 mm in length) have been reported as a reliable marker of an underlying neuropsychiatric disease or disorder. Differences in the dimensions of cava longer than 6 mm associated with a neuropsychiatric impairment could be of possible clinical and forensic significance. METHODS: We obtained 479 brains from autopsied persons (310 males and 169 females, aged 22-89 years) and observed that 110 brains (75 males and 35 females) had CSP, of which the length of CSP was equal to or longer than 6 mm on 69 (49 males and 20 females) of them. These cava were classified into four groups depending on the past medical histories of the autopsied person: five without neuropsychiatric history (asymptomatic CSP), 25 schizophrenic patients, 22 alcoholics, and 17 with a past head trauma (symptomatic CSP). RESULTS: The linear parameters of CSP (i.e. length, width) of the symptomatic and asymptomatic groups were measured and were statistically analyzed. Analysis revealed that the cava in the group of schizophrenic patients were significantly longer and wider. CONCLUSIONS: Discriminant function analysis was used to derive a mathematical formula to classify CSP into one of the groups obtained based on width measurements of the cavum. PMID- 26991978 TI - An open trial of Omega-3 fatty acids for depression in pregnancy. AB - OBJECTIVE: In this flexible-dose, open-label trial, we examined the efficacy of omega-3 fatty acids for the treatment of depression during pregnancy. METHODS: Fifteen pregnant women with major depressive episodes participated. Subjects initially received two capsules per day [0.93 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]; the dose could be increased by one capsule per day every 2 weeks to a maximal dose of 2.8 g. Subjects were assessed with the Edinburgh Postnatal Depression Scale (EPDS) and Hamilton Rating Scale for Depression (HRSD). RESULTS: Average duration of participation in this treatment trial was 8.3 weeks (SD +/- 7.1). Average final dose of EPA + DHA in this flexible dose trial was 1.9 g per day (+/-0.5). The mean reduction in EPDS scores was 40.9% (SD +/- 21.9); the mean decrease in HRSD score was 34.1% (SD +/- 27.1). CONCLUSIONS: This open trial provides data to support the need for randomized controlled dose-finding trials of omega-3 fatty acids in major depressive episodes during pregnancy. PMID- 26991979 TI - Markers for depression in Alzheimer's disease. AB - OBJECTIVE: The aim of this study was to evaluate whether risk factors for depression in the general population are also markers for depression in Alzheimer's disease (AD) and to identify additional disease-specific markers for depression in AD. PATIENTS AND METHODS: A logistic model of five risk factors for depression in the general population was constructed using the data of 217 patients with AD, of whom 63 (29%) suffered from major depressive disorder. In a next step, five potential disease-specific markers were individually added to this model to see whether the strength and predictive power of the model would improve. RESULTS: The multivariate model of five risk factors for depression in the general population was not a good model to predict depression in AD. In this multivariate approach, only 'a history of depression' was an independent marker for depression. The only disease-specific variable that improved the logistic model was 'disability due to AD'. An interaction between these two markers became apparent. CONCLUSIONS: Of the established risk factors for depression in the general population, only 'a history of depression' was found to be an independent marker for depression in AD. 'Disability due to AD' was the only disease-related marker for depression in AD, although this marker cannot be considered specific for AD. The importance of controlling for general risk factors for depression in the search for disease-specific markers for depression in AD is stressed. PMID- 26991980 TI - The usefulness of experience sampling in understanding the urge to move in anorexia nervosa. AB - BACKGROUND: Physical hyperactivity has often been described in anorexia nervosa (AN) patients but up until now in-depth research has been scarce. Experience sampling methodology (ESM), a structured diary technique assessing momentary mental state at random times during the day, may be useful in studying hyperactivity in AN. METHODS: In two single case reports, ESM was used to investigate the variation across time of the urge to move in relation to potentially relevant eliciting conditions such as positive and negative emotions, weight preoccupation and attractiveness. RESULTS: Frequency distribution of the involved variables indicated substantial individual differences between patients. While both patients' tendency to be hyperactive was positively related to their weight preoccupation and negative emotions, in only one patient, the urge to move turned out to be significantly related to (the absence of) positive emotions. CONCLUSIONS: ESM can be useful to test whether general theories of psychopathology apply to specific patients, and it may be conceived as an individually tailored approach to self-monitoring. As such, it may guide the clinician to devise therapeutic interventions in particular patients. PMID- 26991981 TI - Verbal fluency in Parkinson's disease: results of a 2-min fluency test. AB - BACKGROUND: Patients suffering from Parkinson's disease (PD) are often reported to have an impaired performance on tests measuring executive functioning, such as fluency tasks. AIM: To investigate whether verbal fluency is impaired in PD patients (n = 25) compared with healthy controls (n = 15) using a 2-min semantic and phonemic verbal fluency test. A 2-min version of the fluency task was used to allow for more switches between clusters to study retrieval strategies more adequately. RESULTS: No differences in performance on both semantic and phonemic fluency tasks between the PD patients and the control persons were found. Moreover, both groups appeared to use the same retrieval strategies. CONCLUSION: Patients suffering from PD appear to use the same strategies for producing words as healthy controls do. Different pathways may be involved in switching clusters during the fluency task than in other types of switching that may be impaired in PD, such as motor switching and concept-shifting. PMID- 26991982 TI - Evaluation of event-related potentials in Klinefelter syndrome and idiopathic hypogonadotrophic hypogonadism. AB - BACKGROUND: Many studies have evaluated patients with idiopathic hypogonadothropic hypogonadotropism (IHH), but few of these studies utilize event related potentials (P300). AIMS: To assess the cognitive functions of hypergonadotropic vs. hypogonadotropic patients. SETTINGS AND DESIGN: The study group consisted of 41 untreated IHH patients, 32 untreated Klinefelter syndrome (KS) patients, and 30 healthy control subjects. METHODS AND MATERIAL: In this study, the latency and amplitude of P300 was evaluated in 41 untreated IHH and 32 untreated KS patients and compared to healthy control subjects (average age: 30 years). Also evaluated were the patients' hormone levels. RESULTS AND CONCLUSIONS: In this study, the amplitude of P300 was found to be reduced, and the latency prolonged in IHH patients in comparison to KS patients and control subjects. In KS patients, there was no difference in latency of P300, but the amplitude was reduced when compared with the control group. Cognitive dysfunction in patients with hypogonadotropism is related to androgen hormone levels. This deficiency can affect development of the central nervous system (CNS), causing defects of CNS to varying degrees during the perinatal period. Androgen deficiency is considered to exert its effects during the period of cognitive ability development, manifest in IHH patients but not KS patients. PMID- 26991983 TI - Mania as a presenting symptom of Wilson's disease. AB - OBJECTIVE: Wilson's disease commonly presents with neurological or hepatic manifestations. When it presents with only psychiatric symptoms, or with extrapyramidal symptoms secondary to neuroleptic exposure, the diagnosis of underlying Wilson's disease may be missed. METHODS: An 18-year-old boy presented to the psychiatric clinic with a manic syndrome and high propensity for extrapyramidal symptoms to neuroleptic. Initial examination revealed splenomegaly and pancytopenia. Subsequent detection of Kayser-Fleischer ring and typical biochemical findings confirmed the diagnosis of Wilson's disease. RESULTS: While the psychiatric symptoms came under control with lithium carbonate, extrapyramidal symptoms continue to persist even after neuroleptic withdrawal. Pancytopenia thought to be due to hypersplenism persists, and patient has developed features of liver cirrhosis. Treatment with zinc and folic acid has been started, and the patient is under evaluation for treatment with penicillamine. CONCLUSION: The psychiatrist needs to recognize that Wilson's disease can uncommonly present with isolated psychiatric symptoms, including mania. Early and severe extrapyramidal symptoms secondary to neuroleptic exposure in an adolescent age group warrants a detailed evaluation to rule out underlying neuropsychiatric conditions. PMID- 26991984 TI - Psychosis related to methadone withdrawal. AB - We present two cases of typical psychosis related to methadone withdrawal. The two cases, appearing in the adult age, are not related to previous personal or familiar psychiatric illness and do not show the classical symptoms of methadone withdrawal. The appearance of this type of case is an experience repeated in different groups of researchers. In the line of previous investigators, we propose an alteration of neuromodulation in central opiate-dopamine system. PMID- 26991985 TI - A variant of Capgras syndrome with delusional conviction of inanimate doubles in a patient with grandmal epilepsy. AB - BACKGROUND: Capgras syndrome is the most common type of delusional misidentification syndromes. In this phenomenon, the patient believes the delusional conviction that a familiar person has been replaced by imposters. Capgras syndrome was thought to occur in psychotic and organic contexts. It has some rare variants. In one of these rare variants, the patient has the delusion of inanimate doubles. There are reports which regard the relationship between Capgras syndrome and epilepsy as a contributing factor. We present a case of grandmal epilepsy with psychotic features including delusion of inanimate doubles. METHODS: A single case is reported. CASE HISTORY: A 55-year-old woman with long-time history of grandmal epilepsy developed psychosis 3 months prior to her psychiatric referral. She believed that her sons replaced her possessions and furniture continuously. There was no history of previous psychiatric illness, and also there was no evidence of any other organic disorder. CONCLUSION: Previous reports showed Capgras phenomenon as a clinical presentation in epileptic patients. We show that the delusion of doubles of inanimate objects as a variant of Capgras syndrome could also be a clinical presentation in epileptic patients. PMID- 26991986 TI - A case of subacute sclerosing panencephalitis presenting as depression. AB - Subacute sclerosing panencephalitis (SSPE) is rare in adult patients. Clinical presentation in intial phases of SSPE may be non-specific leading to diagnostic delay. We present a 24-year-old patient with depressive syndrome of five months' duration prior to the onset of typical features of SSPE, which is a rare presentation. This patient had responded partially to Sertraline, for a brief period, before he was diagnosed to have SSPE. This case illustrates affective symptoms can be the presenting features of SSPE in adults. PMID- 26991987 TI - Various extraction methods for detection of bistrifluron residues in Asian pear using high-performance liquid chromatography: application to dissipation patterns under open-field conditions. AB - The present study was carried out to develop an analytical method for the detection and quantification of bistrifluron, a benzoylphenylurea compound, in pear using high-performance liquid chromatography with UV detection. Samples were extracted using conventional, AOAC and EN quick, easy, cheap, effective, rugged and safe 'QuEChERS' methods. As expected, conventional and EN-QuEChERS methods gave higher recoveries than AOAC. In addition, interference around the analyte retention time was observed in the conventional method. Thus, the EN-QuEChERS method was selected and validated by studying various parameters, including linearity, limit of detection, limit of quantification (LOQ), recovery and precision. Linearity was excellent, with a correlation coefficient of 0.9998. Recovery rates at three spiking levels (0.05, 0.2 and 1 mg/kg) ranged from 73.76 to 98.66%. Intra- and inter-day precisions, expressed as relative standard deviations, were <6%. The LOQ of 0.05 mg/kg was considerably lower than the maximum residue limit (1 mg/kg) set by the Korean Ministry of Food and Drug Safety. The developed method was successfully applied to open-field pear samples, in which the target analyte was slowly dissipated (55% decline) over 14 days with a half-life of 10.19 days. Notably, the residue levels throughout the period of sample collection (14 days) were lower than the maximum residue limit, indicating that the residue was not hazardous for consumers. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26991988 TI - Comparison of bacterial adhesion to dental materials of polyethylene terephthalate (PET) and polymethyl methacrylate (PMMA) using atomic force microscopy and scanning electron microscopy. AB - The aim of this study was to compare the bacterial adhesion to denture materials of polyethylene terephthalate (PET) and polymethyl methacrylate (PMMA) using atomic force microscopy and scanning electron microscopy. The adhesion forces of living Streptococcus sanguinis and Streptococcus mutans to PET and PMMA were directly measured using atomic force microscopy (AFM) in liquid. Streptococcal biofilms formed on the two material surfaces were investigated and compared using scanning electron microscopy (SEM) and colony-forming units (CFU) counting. Surface roughness and hydrophobicity of PET and PMMA were also measured. The results showed that PET surfaces were significantly smoother and more hydrophilic than PMMA surfaces both with and without a salivary film (p < 0.01). The adhesion forces of S. sanguinis and S. mutans to PET surfaces were significantly stronger than to PMMA surfaces in the absence of a salivary film (p < 0.01). In the presence of a salivary film, the adhesion forces of both bacterial strains to PET and PMMA were significantly decreased (p < 0.01). The adhesion forces of S. mutans to PET surfaces (0.14 nN) were still significantly stronger than to PMMA surfaces (0.09 nN) (p < 0.01). The biofilm formed on PET surfaces was also significantly denser and more than on PMMA surfaces (p < 0.05). In conclusion, the bacterial adhesion to PMMA was significantly less in comparison with PET. PMMA may be preferable for patients who have poor oral hygiene, caries susceptibility, periodontosis, and halitosis. SCANNING 38:665-670, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26991989 TI - Impact of Controlled Induced Hypotension on Cognitive Functions of Patients Undergoing Functional Endoscopic Sinus Surgery. AB - BACKGROUND: Controlled induced hypotension guarantees less blood loss and better visibility of the surgical site. The impact of hypotension on post-operative cognitive functions is still being discussed. The objective of this study was to evaluate the effects of controlled induced hypotension on the cognitive functions of patients undergoing functional endoscopic sinus surgery (FESS). MATERIAL/METHODS: We allocated 47 patients with a good grade of preoperative cognitive functions evaluated with the Mini-Mental State Examination to 3 groups (1 - mild hypotension, 2 - intermediate hypotension, 3 - severe hypotension) according to the degree of mean intraoperative arterial pressure compared with preoperative blood pressure. Cognitive functions were evaluated preoperatively, 6 h, and 30 h postoperatively with standardized tests: the Stroop Test, Trail Making Test (TMT), and Verbal Fluency Test (VFT). A decrease in the test results and increase in the number of mistakes made were considered an impairment of cognitive functions. RESULTS: A total of 47 patients (group 1 - mild hypotension 15, group 2 - intermediate hypotension - 19, group 3 - severe hypotension - 13) were included in the study. A significant decrease was observed in all the 3 groups after Stroop A test 6h postoperatively but it improved 30h postoperatively, without differences between the groups. Neither a significant decrease in the test results nor an increase in the number of mistakes was noted for Stroop B tests, TMT A&B tests and VFT. CONCLUSIONS: The degree of controlled intraoperative hypotension during FESS did not influence the results of psychometric tests. PMID- 26991991 TI - Accessory Tricuspid Valve Leaflet-Morphology, Diagnosis, and Management. AB - Accessory tricuspid valve tissue is a rare entity associated with congenital cardiac anomalies. We report a seven-month-old child who underwent ventricular septal defect closure with excision of an accessory tricuspid valve leaflet and discuss their morphology, clinical presentation, diagnostic modalities, and treatment options. doi: 10.1111/jocs.12731 (J Card Surg 2016;31:324-326). PMID- 26991992 TI - An integrated model of depression, compulsion, and mindfulness among heroin abusers in Taiwan. AB - BACKGROUND AND OBJECTIVES: Prevailing literature explains how depression, compulsion, and mindfulness affect heroin use; however, there is no comprehensive framework that explains their overall relationships. We therefore proposed and examined a hypothetical depression-compulsion-heroin use and mindfulness (DCHm) model. METHODS: We recruited 234 male heroin users. Self-reported levels of depression, mindfulness, compulsion to use, and severity of heroin use were measured. Structural equation modeling was used to examine the proposed DCHm model. RESULTS: Compulsion was a mediator between depression and heroin use. In addition, the DCHm model had satisfactory model fit indices. Depression indirectly affected heroin use through compulsion to use. The moderating effects of mindfulness in the two competing models were compared between the high- and low-mindfulness groups. The DCHm model in the high-mindfulness group had more favorable model fit indices than it did in the low-mindfulness group. CONCLUSIONS: Through learned emotional regulation strategies, addicted people with higher mindfulness were less likely to compulsively take drugs because of a depressive mood than were those with lower mindfulness. Furthermore, effective emotion-regulation strategies should be developed and examined in future studies. SCIENTIFIC SIGNIFICANCE: These results raise questions about the effect of compulsion on heroin use disorders. Mindfulness-based approaches to emotional regulatory strategies should be developed based on these findings. Further experimentation and prospective studies are needed to more fully examine the moderating role of mindfulness on depression and compulsion. PMID- 26991993 TI - Underdiagnosing of antibody-mediated transfusion-related acute lung injury: evaluation of cellular-based versus bead-based techniques. AB - BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To support the diagnosis of antibody-mediated TRALI, HLA and HNA antibodies are tested in involved blood donors. Identification of antibody positive donors is important as exclusion of these donors is part of preventative strategies against TRALI. We compared cellular-based versus bead-based techniques for diagnosis of antibody-mediated TRALI. MATERIALS AND METHODS: All reported TRALI cases in the Netherlands during a 5-year period were evaluated. Donors were screened for the presence of HLA class I and class II antibodies using both cellular-based and bead-based techniques. RESULTS: In total, 100 TRALI cases were reported of which 91 were fully tested. In 113 donors, HLA antibodies were detected of which 84 were only detected by bead-based techniques, 12 only by cellular-based tests and 17 by both assays. Antibody-mediated TRALI was diagnosed in 44 of 91 reported cases. Twenty one (48%) of these cases would not have been identified using only cellular-based assays. CONCLUSION: Bead-based techniques show a higher sensitivity for detecting incompatible donors in TRALI cases than cellular-based assays. These results suggest that the use of bead-based assays will result in a significant reduction of future TRALI reactions as more antibody positive donors will be excluded from future donations. PMID- 26991994 TI - Comparison of D1'- and D1-containing PS II reaction centre complexes under different environmental conditions in Synechocystis sp. PCC 6803. AB - In oxygenic photosynthesis, the D1 protein of Photosystem II is the primary target of photodamage and environmental stress can accelerate this process. The cyanobacterial response to stress includes transcriptional regulation of genes encoding D1, including low-oxygen-induction of psbA1 encoding the D1' protein in Synechocystis sp. PCC 6803. The psbA1 gene is also transiently up-regulated in high light, and its deletion has been reported to increase ammonium-induced photoinhibition. Therefore we investigated the role of D1'-containing PS II centres under different environmental conditions. A strain containing only D1'-PS II centres under aerobic conditions exhibited increased sensitivity to ammonium chloride and high light compared to a D1-containing strain. Additionally a D1'-PS II strain was outperformed by a D1-PS II strain under normal conditions; however, a strain containing low-oxygen-induced D1'-PS II centres was more resilient under high light than an equivalent D1 strain. These D1'-containing centres had chlorophyll a fluorescence characteristics indicative of altered forward electron transport and back charge recombination with the donor side of PS II. Our results indicate D1'-PS II centres are important in the reconfiguration of thylakoid electron transport in response to high light and low oxygen. PMID- 26991990 TI - From embryonic development to human diseases: The functional role of caveolae/caveolin. AB - Caveolae, an almost ubiquitous, structural component of the plasma membrane, play a critical role in many functions essential for proper cell function, including membrane trafficking, signal transduction, extracellular matrix remodeling, and tissue regeneration. Three main types of caveolin proteins have been identified from caveolae since the discovery of caveolin-1 in the early 1990s. All three (Cav-1, Cav-2, and Cav-3) play crucial roles in mammalian physiology, and can effect pathogenesis in a wide range of human diseases. While many biological activities of caveolins have been uncovered since its discovery, their role and regulation in embryonic develop remain largely poorly understood, although there is increasing evidence that caveolins may be linked to lung and brain birth defects. Further investigations are clearly needed to decipher how caveolae/caveolins mediate cellular functions and activities of normal embryogenesis and how their perturbations contribute to developmental disorders. PMID- 26991995 TI - Desmoplastic infantile ganglioglioma with focal cortical dysplasia: A rare double pathology in an infant with history of seizures. AB - We describe an extremely rare case of double pathology arising in an infant girl presenting with a history of intractable seizures, delayed milestones and enlarging head. The pathology included desmoplastic infantile ganglioglioma (DIG) and extensive focal cortical dysplasia in the overlying cortex. While tumors such as ganglioglioma have been commonly described to occur as concomitant pathology with cortical dysplasia, DIG in such an association has not been described in the literature. As DIG are voluminous supratentorial tumors, awareness about such an association is pertinent for correct diagnosis. PMID- 26991996 TI - Effects of Filtering the Center of Pressure Feedback Provided in Visually Guided Mediolateral Weight Shifting. AB - Thirty healthy adults completed a mediolateral weight-shifting balance task in which they were instructed to shift their weight to visually displayed target regions. A model-based filter and three different moving average filters employing 10, 34, and 58 samples were applied to the center of pressure visual feedback that guided the activity. The effects of filter selection on both the displayed feedback and the shift performance were examined in terms of shift time and non-minimum phase behavior. Shift time relates to feedback delay and shift speed, whereas non-minimum phase behavior relates to the force applied in shift initiation. Results indicated that increasing the number of samples in moving average filters (indicative of stronger filtering) significantly increases shift speed and shift initiation force. These effects indicate that careful selection and documentation of data filtering is warranted in future work and suggest opportunities for strategic filtering of visual feedback in clinical weight shifting balance activities in order to improve outcomes based on such feedback. PMID- 26991997 TI - Discovery of 4-(Piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine Derivatives as Akt Inhibitors. AB - A series of 4-(piperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine derivatives was synthesized and evaluated as Akt inhibitors by optimization of a weak screening lead (1). Typically, compounds 5q and 5t significantly improved the Akt1 inhibitory potency with IC50 values of 18.0 and 21.3 nM, respectively, with desirable antiproliferative effect against the cell lines LNCaP and PC-3. The inhibitors 5q and 5t might serve as lead compounds for further exploration of Akt inhibitors as anticancer agents. PMID- 26991998 TI - One-Pot Synthesis of Double Poly(Ionic Liquid) Block Copolymers by Cobalt Mediated Radical Polymerization-Induced Self-Assembly (CMR-PISA) in Water. AB - Amphiphilic double poly(ionic liquid) (PIL) block copolymers are directly prepared by cobalt-mediated radical polymerization induced self-assembly (CMR PISA) in water of N-vinyl imidazolium monomers carrying distinct alkyl chains. The cobalt-mediated radical polymerization of N-vinyl-3-ethyl imidazolium bromide (VEtImBr) is first carried out until high conversion in water at 30 degrees C, using an alkyl bis(acetylacetonate)cobalt(III) adduct as initiator and controlling agent. The as-obtained hydrophilic poly(N-vinyl-3-ethyl imidazolium bromide) (PVEtImBr) is then used as a macroinitiator for the CMR-PISA of N-vinyl 3-octyl imidazolium bromide (VOcImBr). Self-assembly of the amphiphilic PVEtImBr b-PVOcImBr block copolymer, i.e., of PIL-b-PIL-type, rapidly takes place in water, forming polymer nanoparticles consisting of a hydrophilic PVEtImBr corona and a hydrophobic PVOcImBr core. Preliminary investigation into the effect of the size of the hydrophobic block on the dimension of the nanoparticles is also described. PMID- 26991999 TI - Training giraffe (Giraffa camelopardalis reticulata) for front foot radiographs and hoof care. AB - For a large herd of reticulated giraffes, a mainly operant-based training program was created for front foot radiographs and hoof trims in an effort to diagnose and better manage lameness. Behaviors were shaped in a restricted contact set-up, using a positive reinforcement procedure to teach a series of mastered cued behaviors. This training was used to obtain lateral and lateral oblique front foot radiographs for the entire herd. Radiographs were diagnostic for multiple possible causes of lameness including fractures and osteitis of the distal phalangeal bone, hoof overgrowth, osteoarthritis of the distal interphalangeal joint, rotation of the distal phalangeal bone, sesamoid bone cysts, and sole foreign bodies. By training giraffe for foot radiographs and hoof trims, potential causes of lameness could be identified and better managed. Long-term, the results may help zoos identify best practices for managing and preventing lameness in giraffe. Zoo Biol. 35:228-236, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26992001 TI - Characteristics and follow-up of postmarketing studies of conditionally authorized medicines in the EU. AB - AIM: The aim of the present study was to provide an insight into the characteristics and follow-up of postmarketing studies of medicines that were conditionally authorized in the European Union (EU). METHODS: We compiled a list of all postmarketing studies attached as specific obligations to the licence of medicines that were granted conditional marketing authorization from January 2006 to April 2014. Studies were characterized based on their objective, design, status upon marketing authorization (MA) and due data set by authorities. They were linked to online study registrations (Clinicaltrials.gov, ENCePP) to determine completion date. We described and associated characteristics of studies and medicines, and determined whether studies were completed on time. RESULTS: A total of 59 postmarketing studies were requested for 21 conditionally authorized medicines. Most studies had an interventional study design (73%), were ongoing upon MA (61%) and aimed to provide additional data on efficacy (45%). Interventional studies were more often ongoing and providing efficacy data, while observational and other studies were more often new and providing safety data. Frequent grounds for requesting postmarketing studies were 'long-term follow-up' and 'increase data on subpopulations'. Of the 34 studies eligible for follow-up analysis, 26 (76%) were completed and 17 (50%) completed on time. Actual completion time took a median (interquartile range) of 274 (-121 to 556) days longer than expected. CONCLUSIONS: Our results indicated that most postmarketing studies attached to a conditional marketing authorization were eventually completed but that half were completed with a substantial delay. The observations suggest caution when broadening the use of postmarketing studies for resolving uncertainties about benefits and risks after MA. PMID- 26992002 TI - Identification of Risk Factors for Cervical Spine Injury from Pediatric Trauma Registry. AB - BACKGROUND: Cervical spine injuries are rare in children. Our goal is to establish guidelines for cervical spine clearance that are practical for our pediatric population, and, in the process, to reduce the risk of radiation exposure from unnecessary advanced imaging. METHODS: We retrospectively reviewed the records from the registries of two pediatric trauma centers from the past 11 years (January 2002 to June 2013). Patients aged 1 month to 17 years, who had a CT scan of the cervical spine due to trauma indication for possible cervical spine injury, were evaluated. RESULTS: Three risk factors were identified as being significant for the presence of a cervical spine injury. Patients who sustained a cervical spine injury were more likely to be male (p = 0.0261), were more severely injured with a higher injury severity score (ISS 16.39 +/- 15.79 injured vs. 8.7 +/- 9.4 uninjured), and presented with neck tenderness (p = 0.0001). CONCLUSION: In our study, significant cervical spine injury is related to male gender, higher ISS and neck tenderness. PMID- 26992003 TI - Early non-invasive selection of patients at high risk of severe hepatitis C recurrence after liver transplantation. AB - BACKGROUND: The early identification of patients at high risk of severe post liver transplant hepatitis C recurrence is relevant, as these patients may be treated using interferon (IFN)-free regimens. METHODS: In a retrospective study with prospectively collected data, we investigated whether the use of several non invasive methods (fibrosis 4 index [FIB-4], AST-to-platelets ratio index [APRI], enhanced liver fibrosis test [ELF], IFN-gamma-inducible protein 10 [IP-10], and transient elastography by Fibroscan) and their combinations 6 months after transplantation could identify those recipients at higher risk of severe recurrence, defined by the presence of significant fibrosis (F >=2) and/or portal hypertension (hepatic venous pressure gradient >=6 mmHg) 12 months after transplant. Seventy-two hepatitis C virus (HCV)-infected liver transplant patients and 10 recipients in whom HCV was eradicated before transplantation were included in the study. RESULTS: The levels of all biomarkers were significantly higher in HCV-infected recipients than in controls. Among HCV recipients, levels of biomarkers were significantly higher in patients with severe recurrence. Although there were no statistically significant differences between biomarkers, APRI, ELF, and FIB-4 obtained the highest area under the ROC curve values. The combination of serum biomarkers with Fibroscan increased the negative and positive predictive values, although diagnostic accuracy of individual tests was not significantly improved. CONCLUSIONS: Patients at higher risk of severe HCV recurrence can be identified early, 6 months after transplantation, using readily available non-invasive methods. PMID- 26992005 TI - Fracture resistance of endodontically treated mandibular first molars with conservative access cavity and different restorative techniques: An in vitro study. AB - The aim was to investigate in vitro the fracture resistance (FR) of endodontically treated teeth (ETT) with conservative access cavity restored using various direct and indirect restorative materials and techniques. Seventy-two mandibular first molars were equally divided into six groups. Teeth in Group 1 were untreated (controls). In Groups 2, 3, 4, 5 and 6, teeth were restored with amalgam, composite resin, ceramic inlay, ceramic onlay and zirconium crown, respectively. A fracture test was performed on all teeth using a static load. Compared with other groups, teeth in Groups 3 (P < 0.05) and 6 (P < 0.05) had the highest FR values with no significant difference in-between them. Teeth in Group 4 had the lowest FR than other groups (P < 0.05). All restorative techniques tested led to a significant reduction in FR. It is necessary to consider type of fracture when evaluating fracture resistance of endodontically treated teeth. Crowned molars had the highest favourable fractures among the five treatment groups. Although the results of this in vitro study showed variations between tested techniques in ETT with a conservative access cavity, further long-term controlled clinical trials are required to confirm these in vitro findings. PMID- 26992000 TI - Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE). AB - Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2 type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (>=15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control subjects, and found that TSLP expression was restricted to the differentiated suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent with these results in vivo, inducible TSLP protein secretion was higher in CaCl2 differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT) compared to undifferentiated cells of the basal phenotype, following stimulation with the TLR3 ligand poly(I:C). To determine whether food antigens could directly induce epithelial TSLP secretion, differentiated and undifferentiated primary esophageal epithelial cells from EoE and non-EoE subjects were challenged with food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced TSLP secretion in differentiated epithelial cells from both EoE and control cell lines, an effect abolished by budesonide and NF-kappab inhibition. Together, our study shows that specific food antigens can trigger innate immune mediated esophageal TSLP secretion, suggesting that esophageal epithelial cells at the barrier surface may play a significant role in the pathogenesis of EoE by regulating TSLP expression. PMID- 26992004 TI - Factors Predicting Difficulty of Laparoscopic Low Anterior Resection for Rectal Cancer with Total Mesorectal Excision and Double Stapling Technique. AB - BACKGROUND: Laparoscopic sphincter-preserving low anterior resection for rectal cancer is a surgery demanding great skill. Immense efforts have been devoted to identifying factors that can predict operative difficulty, but the results are inconsistent. OBJECTIVE: Our study was conducted to screen patients' factors to build models for predicting the operative difficulty using well controlled data. METHOD: We retrospectively reviewed records of 199 consecutive patients who had rectal cancers 5-8 cm from the anal verge. All underwent laparoscopic sphincter preserving low anterior resections with total mesorectal excision (TME) and double stapling technique (DST). Data of 155 patients from one surgeon were utilized to build models to predict standardized endpoints (operative time, blood loss) and postoperative morbidity. Data of 44 patients from other surgeons were used to test the predictability of the built models. RESULTS: Our results showed prior abdominal surgery, preoperative chemoradiotherapy, tumor distance to anal verge, interspinous distance, and BMI were predictors for the standardized operative times. Gender and tumor maximum diameter were related to the standardized blood loss. Temporary diversion and tumor diameter were predictors for postoperative morbidity. The model constructed for the operative time demonstrated excellent predictability for patients from different surgeons. CONCLUSIONS: With a well-controlled patient population, we have built a predictable model to estimate operative difficulty. The standardized operative time will make it possible to significantly increase sample size and build more reliable models to predict operative difficulty for clinical use. PMID- 26992006 TI - Level of Young People Sexual and Reproductive Health Service Utilization and Its Associated Factors among Young People in Awabel District, Northwest Ethiopia. AB - BACKGROUND: Currently in Ethiopia, young people's sexual and reproductive health services are limited and there is a growing issue of confidentiality and affordability of these health services. Moreover, the available services provided are not sensitive to the special needs of young people. Therefore, this study was aimed to assess young people's sexual and reproductive health service utilization and its associated factors in Awabel district, Northwest Ethiopia. METHODS: A community based cross-sectional study was conducted among 781 randomly selected young people using a pre-tested structured questionnaires in Awabel district, Northwest Ethiopia. Data were entered into Epi data version 3.1 and analyzed using SPSS version 16.0 software. RESULTS: The mean age of respondents were 17.80 (+ 2.65) years. About 41% of young people had utilized sexual and reproductive health services. Young people from families of higher family expenditure, lived with mothers, participated in peer education and lived near to a Health Center were more likely to utilize sexual and reproductive health services. Furthermore, those who had a parental discussion on sexual and reproductive health (AOR (95% C.I): 2.23 (1.43, 3.46)) and ever had sexual intercourse (AOR (95% C.I): 1.88 (1.30, 2.71)) were more likely to utilize the service than their counterparts. On the other hand, those young people lived with their father and had a primary level of educational attainment was less likely to utilize the service. CONCLUSION: Utilization of sexual and reproductive health services is low which needs a great attention where; if not intervened, young people might engage in risky sexual activities. Therefore, it needs a concerted effort from all the concerned bodies to improve their service utilization and thereby reduce the burden of young people's disease and disabilities associated with sexual and reproductive health. PMID- 26992007 TI - Esthetic Outcome of Implant Supported Crowns With and Without Peri-Implant Conditioning Using Provisional Fixed Prosthesis: A Randomized Controlled Clinical Trial. AB - BACKGROUND: Achieving an optimal esthetic result using dental implants is challenging. Fixed implant-supported provisional crowns are often used to customize the emergence profile and to individualize the surrounding peri-implant soft tissue. PURPOSE: The objective of this study is to evaluate whether the use of a provisional implant-supported crown leads to an esthetic benefit on implants that are placed in the esthetic zone. The null hypothesis is that there is no difference between the two study groups. MATERIAL AND METHODS: Twenty single implants (Bone Level, Straumann AG, Basel, Switzerland) were inserted in consecutive patients. After reopening, a randomization process assigned them to either cohort group 1: a provisional phase with soft tissue conditioning using the "dynamic compression technique" or cohort group 2: without a provisional. Implants were finally restored with an all-ceramic crown. Follow-up examinations were performed at 3 and 12 months including implant success and survival, clinical, and radiographic parameters. RESULTS: After 1 year all implants successfully integrated, mean values of combined modPES and WES were 16.7 for group 1 and 10.5 for Group 2. This was statistically significant. Mean bone loss after 1 year was -0.09 and -0.08 for groups 1 and 2, respectively, without being statistically significant. CONCLUSION: A provisional phase with soft tissue conditioning does improve the final esthetic result. PMID- 26992008 TI - Comparison of six disease severity scores for allergic rhinitis against pollen counts a prospective analysis at population and individual level. AB - BACKGROUND: Many different symptom (medication) scores are nowadays used as measures of allergic rhinoconjunctivitis severity in individual patients and in clinical trials. Their differences contribute to the heterogeneity of the primary end-point in meta-analyses, so that calls for symptom (medication) score harmonization have been launched. OBJECTIVE: To prospectively compare six different severity scores for allergic rhinitis (AR) against pollen counts at both population and individual levels. METHODS: Two groups of children with seasonal AR and grass pollen sensitization were recruited in Ascoli, Italy (n = 76) and Berlin, Germany (n = 29). Symptoms and drug intake were monitored daily for 40 and 30 days of the grass pollen season in 2011 (Ascoli) and 2013 (Berlin), respectively, through an Internet-based platform (AllergyMonitor(TM) , TPS Production srl, Rome, Italy). From the gathered data, the informatics platform automatically generated one symptom score (RTSS) and five symptom-medication scores (RC-ACS((c)) , ACS, RTSS[LOCF], RTSS[WC] and AdSS). Values were then statistically normalized for reciprocal comparison and matched against the daily variations of local grass pollen counts (Spearman's rank correlation). RESULTS: The grass pollen counts were higher in Ascoli than in Berlin (peak values 194 vs. 59 grains/m(3) ). At population level, the trajectories of the normalized average values of the six scores differed only slightly in both studies and correlated well with the pollen counts (ranges r(2) : 0.38-0.50 in Ascoli, 0.41-0.56 in Berlin). By contrast, in individual patients, trajectories of different scores were often quite heterogeneous. The RTSS[WC] had a very low discriminatory power and generated in many patients long, flat horizontal segments. CONCLUSIONS: Disease severity scores for seasonal AR, as evaluated via an Internet-based platform, tend to provide similar results at population level but can often produce heterogeneous slopes in individual patients. The choice of the disease severity score might have only a low impact on the outcome of a very large clinical trial, but it may be crucial in the management of individual patients. PMID- 26992011 TI - A Comparison of Expectations of Physicians and Patients with Chronic Pain for Pain Clinic Visits. AB - BACKGROUND: The patient-physician encounter forms the cornerstone of every health service. However, optimal medical outcomes are often confounded by inadequate patient-physician communication. Chronic pain is estimated to affect over 25% of the population. Its effects are multifaceted with patients at increased risk of experiencing emotional and functional disturbances. Therefore, it is crucial to address all components of the patient's pain experience, including beliefs and expectations. It is our understanding that no other study to date has evaluated the expectations of physicians and compared them to those of patients for pain clinic visits. We sought to describe and compare expectations of chronic pain patients and their physicians during a clinic consultation. METHODS: We performed a retrospective review on patients attending the pain clinic for the first time who were enrolled and completed a questionnaire asking their expectations for their clinic visit as well as outcomes that would satisfy and disappoint them. Pain physicians were also included. We compared physicians' to patients' responses and evaluated relationships between patient responses and age, gender, pain location, Pain Self-Efficacy, Pain Catastrophizing Scale, and the Hospital Anxiety and Depression Scale. RESULTS: One hundred chronic pain patients and 10 pain physicians were surveyed. Patients' clinical expectations for visits focused primarily on some pain relief (34%), education on the cause of pain (24%), and a definitive diagnosis (18%). Physician's expectations included formulation and communication of a management plan (70%), patient assessment for cause of pain (50%), and the education of patients on the cause of pain (40%) as important aims. Pain relief would satisfy the majority of patients (74%) and physicians (70%). No improvement would cause greatest dissatisfaction for patients (52%), but causing more harm would be disappointing to physicians (50%). Gender, age, pain location, and sleep quality all significantly influenced patients' expectations and affective pain comorbidities. CONCLUSION: We found some agreement and some discordance of clinical expectations between pain patients and physicians. Patient factors may also impact on expectations and comorbidities. Findings from this study will help doctors consider patients' expectations in planning pain clinic visits, improve patient-doctor communication and pain management, and may lead to further hypothesis-driven studies. PMID- 26992009 TI - Clonal Structure and Characterization of Staphylococcus aureus Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, spa Types, Clonal Complexes, and Genetic Markers. AB - The aim of current study was to examine clonal structure and genetic profile of invasive Staphylococcus aureus isolates recovered from infants and children treated at the Jagiellonian University Children's Hospital of Krakow, Poland. The 107 invasive S. aureus isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, spa typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 S. aureus isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, spa-CC 002), CC45 (spa-CC 015), CC7 or CC15 (t084, t091, spa-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, spa types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including erm(A), sea (N315), egc-cluster, chp was significantly higher in isolates obtained from children in this age group. The spa types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas spa type t008, CC8 and presence of splE was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5 years, although the majority of invasive infections was associated with MSSA strains. Moreover, an association between age group of children from the study population and a specific strain genotype (spa type, clonal complex or genetic content) was observed among the patients. PMID- 26992010 TI - Adaptive divergence despite strong genetic drift: genomic analysis of the evolutionary mechanisms causing genetic differentiation in the island fox (Urocyon littoralis). AB - The evolutionary mechanisms generating the tremendous biodiversity of islands have long fascinated evolutionary biologists. Genetic drift and divergent selection are predicted to be strong on islands and both could drive population divergence and speciation. Alternatively, strong genetic drift may preclude adaptation. We conducted a genomic analysis to test the roles of genetic drift and divergent selection in causing genetic differentiation among populations of the island fox (Urocyon littoralis). This species consists of six subspecies, each of which occupies a different California Channel Island. Analysis of 5293 SNP loci generated using Restriction-site Associated DNA (RAD) sequencing found support for genetic drift as the dominant evolutionary mechanism driving population divergence among island fox populations. In particular, populations had exceptionally low genetic variation, small Ne (range = 2.1-89.7; median = 19.4), and significant genetic signatures of bottlenecks. Moreover, islands with the lowest genetic variation (and, by inference, the strongest historical genetic drift) were most genetically differentiated from mainland grey foxes, and vice versa, indicating genetic drift drives genome-wide divergence. Nonetheless, outlier tests identified 3.6-6.6% of loci as high FST outliers, suggesting that despite strong genetic drift, divergent selection contributes to population divergence. Patterns of similarity among populations based on high FST outliers mirrored patterns based on morphology, providing additional evidence that outliers reflect adaptive divergence. Extremely low genetic variation and small Ne in some island fox populations, particularly on San Nicolas Island, suggest that they may be vulnerable to fixation of deleterious alleles, decreased fitness and reduced adaptive potential. PMID- 26992012 TI - Left Ventricular Global Longitudinal Strain in HER-2 + Breast Cancer Patients Treated with Anthracyclines and Trastuzumab Who Develop Cardiotoxicity Is Associated with Subsequent Recovery of Left Ventricular Ejection Fraction. AB - AIM: The combination of anthracyclines (AC) and trastuzumab (TRZ) is highly effective in patients with aggressive HER-2 + breast cancer, but has a significant risk of cardiotoxicity (CT). Trastuzumab-induced CT may be reversible. The aim of this study was to identify echocardiographic parameters associated with recovery of left ventricular ejection fraction (LVEF) in patients who developed CT after AC and TRZ treatment. METHODS AND RESULTS: Women with newly diagnosed breast cancer treated with AC followed by TRZ and monitored with serial echocardiograms were retrospectively studied. Left ventricular end diastolic and systolic volumes, LVEF, and global longitudinal strain (GLS) were examined. Development and reversibility of CT were defined based on changes in LVEF according to the 2014 ASE/EACVI recommendations. Cox analysis was used to determine the association of echocardiographic variables with the subsequent development and reversibility of CT. Ninety-five patients underwent 5 echocardiograms or more in a 17-month (13-28 months) follow-up period. Nineteen patients (20%) developed CT. Left ventricular volumes, LVEF, and GLS measured after AC completion identified the subsequent development of CT. Of the 19 patients with CT, the LVEF partially or fully recovered in 13 (68%). GLS at the time of CT diagnosis was associated with subsequent recovery of LVEF (P = 0.004). CONCLUSION: In patients with breast cancer treated with AC and TRZ who develop CT, GLS at the time of CT diagnosis is associated with subsequent recovery of LVEF and may be useful for risk stratification and to guide treatment. PMID- 26992013 TI - Perturbed Mucosal Immunity and Dysbiosis Accompany Clinical Disease in a Rat Model of Spondyloarthritis. AB - OBJECTIVE: The HLA-B27/beta2 -microglobulin (beta2 m)-transgenic (Tg) rat is a leading model of B27-associated spondyloarthritis (SpA), and the disease is dependent on the presence of intestinal bacteria. Previous studies have shown that adult HLA-B27/beta2 m-Tg rats have an altered intestinal microbiota. This study sought to better define the age-dependent changes to both mucosal immune function and dysbiosis in this rat model of SpA. METHODS: Intestinal contents were collected from wild-type and HLA-B27/beta2 m-Tg rats postweaning (ages 3 and 6 weeks), at disease onset (age 10 weeks), and after the establishment of disease (ages >=16 weeks). The microbial community structure was determined by 16S ribosomal RNA sequencing and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Mucosal and systemic Th1, Th17, and Treg cell responses were analyzed by flow cytometry, as was the frequency of IgA-coated intestinal bacteria. Intestinal expression of inflammatory cytokines and antimicrobial peptides (AMPs) was determined by qRT-PCR. RESULTS: An inflammatory cytokine signature and elevated AMP expression during the postweaning period preceded the development of clinical bowel inflammation and dysbiosis in HLA-B27/beta2 m-Tg rats. An early and sustained expansion of the Th17 cell pool was specifically observed in the cecal and colonic mucosa of HLA-B27/beta2 m-Tg rats. Strongly elevated intestinal colonization of Akkermansia muciniphila and an increased frequency of IgA-coated fecal bacteria were significantly associated with expression of HLA-B27 and arthritis development. CONCLUSION: HLA-B27/beta2 m expression in this rat model renders the host hyperresponsive to microbial antigens from infancy. Early activation of innate immunity and expansion of a mucosal Th17 signature are soon followed by dysbiosis in HLA-B27/beta2 m-Tg animals. The pathologic processes of perturbed mucosal immunity and dysbiosis strongly merit further study in both prediseased and diseased populations of patients with SpA. PMID- 26992015 TI - In the endoscopy unit: Summary. PMID- 26992014 TI - Energetic Landscape of MDM2-p53 Interactions by Computational Mutagenesis of the MDM2-p53 Interaction. AB - The ubiquitin ligase MDM2, a principle regulator of the tumor suppressor p53, plays an integral role in regulating cellular levels of p53 and thus a prominent role in current cancer research. Computational analysis used MUMBO to rotamerize the MDM2-p53 crystal structure 1YCR to obtain an exhaustive search of point mutations, resulting in the calculation of the DeltaDeltaG comprehensive energy landscape for the p53-bound regulator. The results herein have revealed a set of residues R65-E69 on MDM2 proximal to the p53 hydrophobic binding pocket that exhibited an energetic profile deviating significantly from similar residues elsewhere in the protein. In light of the continued search for novel competitive inhibitors for MDM2, we discuss possible implications of our findings on the drug discovery field. PMID- 26992016 TI - Alzheimer's disease with cerebrovascular disease: current status in the Asia Pacific region. AB - BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease. PMID- 26992018 TI - Little red floaters: gas vesicles in an enterobacterium. PMID- 26992017 TI - Genetic anticipation in BRCA1/BRCA2 families after controlling for ascertainment bias and cohort effect. AB - BACKGROUND: Genetic anticipation, the earlier onset of disease in successive generations, has been reported in hereditary breast and ovarian cancer syndrome (HBOC), but little is known about its underlying mechanisms. Ascertainment bias has been suggested as a reason in previous studies. Likewise, cohort effect, which may be caused by environmental factors, can be misinterpreted as genetic anticipation. METHODS: The authors reviewed the pedigrees of 176 kindreds, segregating those with deleterious mutations in breast cancer genes 1 and 2 (BRCA1/BRCA2) who had at least 2 consecutive generations of the same cancer (breast or ovarian). By using mutation probabilities as analytical weights in weighted random-effect models, generational differences in the age at onset of breast/ovarian cancer were calculated. The analyses were further controlled for ascertainment bias by excluding probands and adjusting for birth-cohort effect in the anticipation models. RESULTS: The mean age at the onset of breast cancer for the probands' generation was 41.9 years, which was 6.8 years and 9.8 years earlier than the parents' and grandparents' generations, respectively. The anticipation effect for breast cancer remained significant after excluding the probands. There was a birth-cohort effect: patients who were born in 1930s and 1940s had breast cancer 5.0 years and 7.6 years earlier than patients who were born before 1920. The difference in breast cancer age of onset across generations was no longer significant after adjusting for birth-cohort effect. CONCLUSIONS: The observed anticipation effect was driven mainly by a decrease in age of onset across birth cohorts, underscoring the need for risk-reducing interventions that target changing environmental/lifestyle factors in BRCA1/BRCA2 carriers. Cancer 2016;122:1913-20. (c) 2016 American Cancer Society. PMID- 26992019 TI - The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations. AB - Historically low breast cancer incidence rates among Asian women have risen worldwide; purportedly due to the adoption of a "Western" life style among younger generations (i.e., the more recent birth cohorts). However, no study has simultaneously compared birth cohort effects between both younger and older women in different Asian and Western populations. Using cancer registry data from rural and urban China, Singapore and the United States (1990-2008), we estimated age standardized incidence rates (ASR), annual percentage change (EAPC) in the ASR, net drifts, birth cohort specific incidence rates and cohort rate ratios (CRR). Younger (30-49 years, 1943-1977 birth cohorts) and older women (50-79 years; 1913 1957 birth cohorts) were assessed separately. CRRs among Chinese populations were estimated using birth cohort specific rates with US non-Hispanic white women (NHW) serving as the reference population with an assigned CRR of 1.0. We observed higher EAPCs and net drifts among those Chinese populations with lower ASRs. Similarly, we observed the most rapidly increasing cohort-specific incidence rates among those Chinese populations with the lowest baseline CRRs. Both trends were more significant among older than younger women. Average CRRs were 0.06-0.44 among older and 0.18-0.81 among younger women. Rapidly rising cohort specific rates have narrowed the historic disparity between Chinese and US NHW breast cancer populations particularly in regions with the lowest baseline rates and among older women. Future analytic studies are needed to investigate risk factors accounting for the rapid increase of breast cancer among older and younger women separately in Asian populations. PMID- 26992020 TI - Comprehensive and Practical Vision System for Self-Driving Vehicle Lane-Level Localization. AB - Vehicle lane-level localization is a fundamental technology in autonomous driving. To achieve accurate and consistent performance, a common approach is to use the LIDAR technology. However, it is expensive and computational demanding, and thus not a practical solution in many situations. This paper proposes a stereovision system, which is of low cost, yet also able to achieve high accuracy and consistency. It integrates a new lane line detection algorithm with other lane marking detectors to effectively identify the correct lane line markings. It also fits multiple road models to improve accuracy. An effective stereo 3D reconstruction method is proposed to estimate vehicle localization. The estimation consistency is further guaranteed by a new particle filter framework, which takes vehicle dynamics into account. Experiment results based on image sequences taken under different visual conditions showed that the proposed system can identify the lane line markings with 98.6% accuracy. The maximum estimation error of the vehicle distance to lane lines is 16 cm in daytime and 26 cm at night, and the maximum estimation error of its moving direction with respect to the road tangent is 0.06 rad in daytime and 0.12 rad at night. Due to its high accuracy and consistency, the proposed system can be implemented in autonomous driving vehicles as a practical solution to vehicle lane-level localization. PMID- 26992021 TI - Image Segmentation With Eigenfunctions of an Anisotropic Diffusion Operator. AB - We propose the eigenvalue problem of an anisotropic diffusion operator for image segmentation. The diffusion matrix is defined based on the input image. The eigenfunctions and the projection of the input image in some eigenspace capture key features of the input image. An important property of the model is that for many input images, the first few eigenfunctions are close to being piecewise constant, which makes them useful as the basis for a variety of applications, such as image segmentation and edge detection. The eigenvalue problem is shown to be related to the algebraic eigenvalue problems resulting from several commonly used discrete spectral clustering models. The relation provides a better understanding and helps developing more efficient numerical implementation and rigorous numerical analysis for discrete spectral segmentation methods. The new continuous model is also different from energy-minimization methods such as active contour models in that no initial guess is required for in the current model. A numerical implementation based on a finite-element method with an anisotropic mesh adaptation strategy is presented. It is shown that the numerical scheme gives much more accurate results on eigenfunctions than uniform meshes. Several interesting features of the model are examined in numerical examples, and possible applications are discussed. PMID- 26992022 TI - Orientation-Independent Empirical Mode Decomposition for Images Based on Unconstrained Optimization. AB - This paper introduces a 2D extension of the empirical mode decomposition (EMD), through a novel approach based on unconstrained optimization. EMD is a fully data driven method that locally separates, in a completely data-driven and unsupervised manner, signals into fast and slow oscillations. The present proposal implements the method in a very simple and fast way, and it is compared with the state-of-the-art methods evidencing the advantages of being computationally efficient, orientation-independent, and leads to better performances for the decomposition of amplitude modulated-frequency modulated (AM FM) images. The resulting genuine 2D method is successfully tested on artificial AM-FM images and its capabilities are illustrated on a biomedical example. The proposed framework leaves room for an nD extension (n > 2 ). PMID- 26992023 TI - Codec and GOP Identification in Double Compressed Videos. AB - Video content is routinely acquired and distributed in a digital compressed format. In many cases, the same video content is encoded multiple times. This is the typical scenario that arises when a video, originally encoded directly by the acquisition device, is then re-encoded, either after an editing operation, or when uploaded to a sharing website. The analysis of the bitstream reveals details of the last compression step (i.e., the codec adopted and the corresponding encoding parameters), while masking the previous compression history. Therefore, in this paper, we consider a processing chain of two coding steps, and we propose a method that exploits coding-based footprints to identify both the codec and the size of the group of pictures (GOPs) used in the first coding step. This sort of analysis is useful in video forensics, when the analyst is interested in determining the characteristics of the originating source device, and in video quality assessment, since quality is determined by the whole compression history. The proposed method relies on the fact that lossy coding is an (almost) idempotent operation. That is, re-encoding a video sequence with the same codec and coding parameters produces a sequence that is similar to the former. As a consequence, if the second codec in the chain does not significantly alter the sequence, it is possible to analyze this sort of similarity to identify the first codec and the adopted GOP size. The method was extensively validated on a very large data set of video sequences generated by encoding content with a diversity of codecs (MPEG-2, MPEG-4, H.264/AVC, and DIRAC) and different encoding parameters. In addition, a proof of concept showing that the proposed method can also be used on videos downloaded from YouTube is reported. PMID- 26992024 TI - Single Image Super-Resolution Using Local Geometric Duality and Non-Local Similarity. AB - Super-resolution (SR) from a single image plays an important role in many computer vision applications. It aims to estimate a high-resolution (HR) image from an input low- resolution (LR) image. To ensure a reliable and robust estimation of the HR image, we propose a novel single image SR method that exploits both the local geometric duality (GD) and the non-local similarity of images. The main principle is to formulate these two typically existing features of images as effective priors to constrain the super-resolved results. In consideration of this principle, the robust soft-decision interpolation method is generalized as an outstanding adaptive GD (AGD)-based local prior. To adaptively design weights for the AGD prior, a local non-smoothness detection method and a directional standard-deviation-based weights selection method are proposed. After that, the AGD prior is combined with a variational-framework-based non-local prior. Furthermore, the proposed algorithm is speeded up by a fast GD matrices construction method, which primarily relies on the selective pixel processing. The extensive experimental results verify the effectiveness of the proposed method compared with several state-of-the-art SR algorithms. PMID- 26992025 TI - Low-Rank Matrix Factorization With Adaptive Graph Regularizer. AB - In this paper, we present a novel low-rank matrix factorization algorithm with adaptive graph regularizer (LMFAGR). We extend the recently proposed low-rank matrix with manifold regularization (MMF) method with an adaptive regularizer. Different from MMF, which constructs an affinity graph in advance, LMFAGR can simultaneously seek graph weight matrix and low-dimensional representations of data. That is, graph construction and low-rank matrix factorization are incorporated into a unified framework, which results in an automatically updated graph rather than a predefined one. The experimental results on some data sets demonstrate that the proposed algorithm outperforms the state-of-the-art low-rank matrix factorization methods. PMID- 26992026 TI - Insights into Medium-chain Acyl-CoA Dehydrogenase Structure by Molecular Dynamics Simulations. AB - The medium-chain acyl-CoA dehydrogenase (MCAD) is a mitochondrial enzyme that catalyzes the first step of mitochondrial fatty acid beta-oxidation (mFAO) pathway. Its deficiency is the most common genetic disorder of mFAO. Many of the MCAD disease-causing variants, including the most common p.K304E variant, show loss of function due to protein misfolding. Herein, we used molecular dynamics simulations to provide insights into the structural stability and dynamic behavior of MCAD wild-type (MCADwt) and validate a structure that would allow reliable new studies on its variants. Our results revealed that in both proteins the flavin adenine dinucleotide (FAD) has an important structural role on the tetramer stability and also in maintaining the volume of the enzyme catalytic pockets. We confirmed that the presence of substrate changes the dynamics of the catalytic pockets and increases FAD affinity. A comparison between the porcine MCADwt (pMCADwt) and human MCADwt (hMCADwt) structures revealed that both proteins are essentially similar and that the reversion of the double mutant E376G/T255E of hMCAD enzyme does not affect the structure of the protein neither its behavior in simulation. Our validated hMCADwt structure is crucial for complementing and accelerating the experimental studies aiming for the discovery and development of potential stabilizers of MCAD variants as candidates for the treatment of MCAD deficiency (MCADD). PMID- 26992027 TI - Hepatitis C Treatment in 2016: Reasons to Be an OPTIMIST. PMID- 26992028 TI - Effects of exposure to gradient magnetic fields emitted by nuclear magnetic resonance devices on clonogenic potential and proliferation of human hematopoietic stem cells. AB - This study investigates effects of gradient magnetic fields (GMFs) emitted by magnetic resonance imaging (MRI) devices on hematopoietic stem cells. Field measurements were performed to assess exposure to GMFs of staff working at 1.5 T and 3 T MRI units. Then an exposure system reproducing measured signals was realized to expose in vitro CD34+ cells to GMFs (1.5 T-protocol and 3 T protocol). CD34+ cells were obtained by Fluorescence Activated Cell Sorting from six blood donors and three MRI-exposed workers. Blood donor CD34+ cells were exposed in vitro for 72 h to 1.5 T or 3 T-protocol and to sham procedure. Cells were then cultured and evaluated in colony forming unit (CFU)-assay up to 4 weeks after exposure. Results showed that in vitro GMF exposure did not affect cell proliferation but instead induced expansion of erythroid and monocytes progenitors soon after exposure and for the subsequent 3 weeks. No decrease of other clonogenic cell output (i.e., CFU granulocyte/erythroid/macrophage/megakaryocyte and CFU-granulocyte/macrophage) was noticed, nor exposed CD34+ cells underwent the premature exhaustion of their clonogenic potential compared to sham-exposed controls. On the other hand, pilot experiments showed that CD34+ cells exposed in vivo to GMFs (i.e., samples from MRI workers) behaved in culture similarly to sham-exposed CD34+ cells, suggesting that other cells and/or microenvironment factors might prevent GMF effects on hematopoietic stem cells in vivo. Accordingly, GMFs did not affect the clonogenic potential of umbilical cord blood CD34+ cells exposed in vitro together with the whole mononuclear cell fraction. PMID- 26992029 TI - Outcomes of modified endoscopic Lothrop in aspirin-exacerbated respiratory disease with nasal polyposis. AB - BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) and chronic rhinosinusitis with nasal polyps (CRSwNP) are often reported to be recalcitrant to standard medical and surgical intervention. Failure rates of standard endoscopic sinus surgery in these patients are reported to be as high as 90%. We review the outcomes for our cohort of AERD patients undergoing endoscopic sinus surgery and endoscopic modified Lothrop procedure (EMLP). METHODS: Data was collected prospectively between January 2001 and December 2013. Information including demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22), Lund-Mackay scores, and endoscopic ostium assessment were collected for up to 5 years. Minimum follow-up was 6 months. RESULTS: A total of 31 AERD patients underwent complete sphenoethmoidectomy, maxillary antrostomy and EMLP during the study period with an average follow-up of 36 months. Polyp recurrence was seen in a total of 18 patients (58%). Seven patients required revision EMLP following initial surgery demonstrating a failure rate of 22.5%. AERD patients had a statistically significant increased risk of both nasal polyps recurrence and need for revision surgery. Revision EMLP was needed due to recurrence of nasal polyps in 6 cases and frontal ostium stenosis in a single case. Time to revision EMLP was similar between the groups. CONCLUSION: Complete sphenoethmoidectomy, maxillary antrostomy, and EMLP is successful in a significant majority of patients with AERD and CRSwNP. It is well tolerated with a low complication rate and facilitates successful ongoing medical management of the condition in patients with AERD. PMID- 26992030 TI - Likelihood and predictors of detention in patients with personality disorder compared with other mental disorders: A retrospective, quantitative study of Mental Health Act assessments. AB - BACKGROUND: The UK guidelines on the treatment of personality disorder recommend avoiding compulsory treatment except in extreme situations. Little is known about how often patients with personality disorder are detained or how this compares with the treatment of other mental disorders. OBJECTIVES: Our aim is to test the hypothesis that people with personality disorder are infrequently detained under the Mental Health Act (MHA) and that risk factors associated with detention are the same as those for people with other mental disorders. METHOD: We used a retrospective, quantitative study of MHA assessments. RESULTS: Of the 2 087 assessments undertaken, 204 (9.8%) patients had a diagnosis of personality disorder; 40.7% of assessments in the personality disorder group resulted in detention, as did 69.7% of patients with other mental disorders. A higher proportion of people with personality disorder received no intervention following assessment compared with those with other mental disorders (20.6% vs. 4.7%, p < 0.001). Study centre and a history of admission were risk factors for detention in both groups. Risk was a predictor of detention in those with other mental disorders. CONCLUSIONS: Detention rates in patients with personality disorder are lower than those for other disorders but are still substantial. Risk factors for detention in patients with personality disorder differ from those with other mental disorders. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26992031 TI - The international migration of dentists: directions for research and policy. AB - In 2010, the World Health Organization Global Code of Practice for International Recruitment of Health Personnel (the WHO Code) was adopted by the 193 Member States of the WHO. The WHO Code is a tool for global diplomacy, providing a policy framework to address the challenges involved in managing dentist migration, as well as improving the retention of dental personnel in source countries. The WHO Code recognizes the importance of migrant dentist data to support migration polices; minimum data on the inflows, outflows and stock of dentists are vital. Data on reasons for dentist migration, job satisfaction, cultural adaptation issues, geographic distribution and practice patterns in the destination country are important for any policy analysis on dentist migration. Key challenges in the implementation of the WHO Code include the necessity to coordinate with multiple stakeholders and the lack of integrated data on dentist migration and the lack of shared understanding of the interrelatedness of workforce migration, needs and planning. The profession of dentistry also requires coordination with a number of private and nongovernmental organizations. Many migrant dentist source countries, in African and the South-Asian WHO Regions, are in the early stages of building capacity in dentist migration data collection and research systems. Due to these shortcomings, it is prudent that developed countries take the initiative to pursue further research into the migration issue and respond to this global challenge. PMID- 26992032 TI - Phonological processing in children with specific language impairment with and without reading difficulties. AB - BACKGROUND: Specific language impairment (SLI) is heterogeneous and identifying subgroups within it may help explain the aetiology of the condition. Phonological processing abilities distinguish between children with SLI who do and do not have reading decoding impairments (RDIs). AIMS: To probe different levels of phonological processing in children with SLI with and without RDI to investigate the cognitive basis of these differences. METHODS & PROCEDURES: A total of 64 children aged 5-17 years were classified using the results of standardized language and single-word reading tests into those with no SLI and no RDI (No SLI/No RDI) (N = 18), no SLI but with RDI (No SLI/RDI) (N = 4, not included in analyses because of the small number), SLI/No RDI (N = 20), and SLI/RDI (N = 22). The groups were compared on a range of tasks engaging different levels of phonological processing (input and output processing and phonological awareness). OUTCOMES & RESULTS: The SLI/RDI group was distinguished from the SLI/No RDI and No SLI/No RDI groups by more errors in the longer items in non-word repetition and by poorer phonological awareness. Non-word discrimination scores indicated a gradient of performance across groups that was not associated with a qualitatively different pattern of performance. CONCLUSIONS & IMPLICATIONS: This is the first study contrasting input and output processes associated with phonological processing. The results suggest that deficits in SLI plus RDI may be associated with impairment in actively maintaining phonological representations for phonological processing, which is not present in those without RDI and which leads to reading decoding difficulties. PMID- 26992033 TI - Phenotypic switching of vascular smooth muscle cells in the 'normal region' of aorta from atherosclerosis patients is regulated by miR-145. AB - Switching of vascular smooth muscle cells (VSMCs) from a contractile phenotype to an adverse proliferative phenotype is a hallmark of atherosclerosis or vascular restenosis. However, the genetic modulators responsible for this switch have not been fully elucidated in humans nor have they been correlated with clinical abnormalities. This study investigated genetic mechanisms involved in phenotypic switching of VSMCs at non-defect areas of the aorta in patients with atherosclerosis. Aortic wall samples were obtained from patients with (N = 53) and without (N = 27) atherosclerosis undergoing cardiovascular surgery. Vascular smooth muscle cell cultures were generated, and expression of microRNA-145 (miR 145), its target gene Kruppel-Like Factor 5 (KLF5) and Myocardin (MYOCD, a smooth muscle-specific transcriptional coactivator) were analysed using RT-qPCR, along with expression of relevant proteins. Vascular smooth muscle cells were transduced with miR-145 inhibitor and mimic to determine the effect of miR-145 expression on VSMC proliferation. miR-145 expression decreased while KLF5 expression increased in atherosclerotic aortas. Atherosclerotic samples and VSMCs had decreased expression of contractile markers calponin and alpha smooth muscle actin (alpha-SMA) and MYOCD. miR-145 inhibitor-transduced VSMCs from non atherosclerotic patients showed decreased expression of calponin and alpha-SMA and increased proliferation compared with non-transduced controls, and these levels were close to those of atherosclerotic patients. miR-145 mimic-transduced VSMCs from atherosclerotic patients showed increased expression of calponin and alpha-SMA and decreased proliferation compared with non-transduced controls, and these levels were close to those found in non-atherosclerotic patients. These data demonstrate that miR-145 modulates the phenotypic switch of VSMCs from a contractile to a proliferative state via KLF5 and MYOCD in atherosclerosis. PMID- 26992035 TI - The spatial-temporal expression and functional divergence of bach homologs in zebrafish Danio rerio. AB - The spatial-temporal expressions of bach1a, bach1b, bach2a and bach2b in early development of zebrafish Danio rerio embryos were examined in the present study by whole mount in situ hybridization. Transcripts of all genes were found at the one cell stage, suggesting that these four genes are maternally inherited. From the phylogenetic analyses, Bach1a and Bach1b from fishes form a well-supported group with two sub-groups. Bach2a and Bach2b, however, did not fall into one clade, suggesting that Bach2 proteins diverged faster or earlier than Bach1 proteins in fishes. The differentially regulated expression of the exocrine zymogen (such as the trypsin-like gene, tryl) of both paralogs of bach1 and bach2, respectively, showed that their functions are still active and already divergent, coinciding with subfunction partitioning. PMID- 26992034 TI - The green tea polyphenol EGCG inhibits E. coli biofilm formation by impairing amyloid curli fibre assembly and downregulating the biofilm regulator CsgD via the sigma(E) -dependent sRNA RybB. AB - In bacterial biofilms, which are often involved in chronic infections, cells are surrounded by a self-produced extracellular matrix that contains amyloid fibres, exopolysaccharides and other biopolymers. The matrix contributes to the pronounced resistance of biofilms against antibiotics and host immune systems. Being highly inflammatory, matrix amyloids such as curli fibres of Escherichia coli can also play a role in pathogenicity. Using macrocolony biofilms of commensal and pathogenic E. coli as a model system, we demonstrate here that the green tea polyphenol epigallocatachin gallate (EGCG) is a potent antibiofilm agent. EGCG virtually eliminates the biofilm matrix by directly interfering with the assembly of curli subunits into amyloid fibres, and by triggering the sigma(E) cell envelope stress response and thereby reducing the expression of CsgD - a crucial activator of curli and cellulose biosynthesis - due to csgD mRNA targeting by the sigma(E) -dependent sRNA RybB. These findings highlight EGCG as a potential adjuvant for antibiotic therapy of biofilm-associated infections. Moreover, EGCG may support therapies against pathogenic E. coli that produce inflammatory curli fibres along with Shigatoxin. PMID- 26992036 TI - Direct Time-Domain Observation of Conformational Relaxation in Gas-Phase Cold Collisions. AB - Cooling molecules in the gas phase is important for precision spectroscopy, cold molecule physics, and physical chemistry. Measurements of conformational relaxation cross sections shed important light on potential energy surfaces and energy flow within a molecule. However, gas-phase conformational cooling has not been previously observed directly. In this work, we directly observe conformational dynamics of 1,2-propanediol in cold (6 K) collisions with atomic helium using microwave spectroscopy and buffer-gas cooling. Precise knowledge and control of the collisional environment in the buffer-gas allows us to measure the absolute collision cross-section for conformational relaxation. Several conformers of 1,2-propanediol are investigated and found to have relaxation cross sections with He ranging from sigma=4.7(3.0)*10(-18) cm(2) to sigma>5*10(-16) cm(2). Our method is applicable to a broad class of molecules and could be used to provide information about the potential energy surfaces of previously uninvestigated molecules. PMID- 26992037 TI - Unusual case of digestive bleeding nine months after a cephalic pancreaticoduodenectomy (CPD). AB - INTRODUCTION: Post-pancreaticoduodenectomy hemorrhage is mostly due to the gastroduodenal artery stump erosion. The diagnosis of arterial bleeding is done by digestive endoscopy, selective angiography or video capsule endoscopy. On failure of etiological research, surgery is the last resort despite its technical difficulties. CASE PRESENTATION: A 63 years-old woman was admitted in surgery, nine months after cephalic pancreaticoduodenectomy for a pain of the right hypochondria combined with a pneumoperitoneum, after a 3rd episode of hemorrhage. Exploratory laparotomy is performed after a third hemorrhagic episode and failure of etiological research. Bleeding from the gastroduodenal artery stump was discovered and successfully treated. DISCUSSION: Post-pancreaticoduodenectomy hemorrhage can occur very late. In these cases, a secondary arterial erosion obstructed by left hemi-liver should not be excluded. In these cases, despite the technical risks, surgery is required. CONCLUSION: The failure of the means used for diagnostic must lead to the surgery right away, despite operating risk. PMID- 26992038 TI - Brain derived neurotrophic factor in multiple sclerosis: effect of 24 weeks endurance and resistance training. AB - BACKGROUND AND PURPOSE: Brain derived neurotrophic factor (BDNF) is suggested to play a neuroprotective role in multiple sclerosis (MS). However, the BDNF response to long-term exercise in MS remains unknown. Our objective was to compare resting BDNF profiles of healthy controls (HCs) and persons with relapsing-remitting MS (RRMS) and to investigate the impact of a 24-week exercise intervention on serum BDNF release in MS. METHODS: At baseline, blood BDNF levels were assessed in MS (n = 22, mean Expanded Disability Status Scale 2.6 +/- 0.2, mean age 43 +/- 2 years) and HCs (n = 19, mean age 47 +/- 1 year). Next, persons with MS were randomized to an exercise intervention group (EX, n = 15) or a sedentary control group (SED, n = 7) completing a 24-week randomized controlled trial. In persons with MS, muscle strength, exercise tolerance and body composition were assessed, as compliance measures, at baseline and after 24 weeks. RESULTS: At baseline, the BDNF concentration of persons with RRMS was 21% lower than HCs. Following 24 weeks of intervention, changes in BDNF concentrations differed significantly between EX and SED. In particular, within EX BDNF concentrations increased 13.9% +/- 8.8%, whereas it decreased 10.5% +/- 4.1% within SED. Furthermore, 24 weeks of exercise induced changes in the compliance measures between EX and SED. In addition, within EX muscle strength, exercise tolerance and lean tissue mass improved, whereas these remained stable within SED. CONCLUSION: In conclusion, BDNF concentration of persons with RRMS was lower compared to HCs and increased after 24 weeks of exercise in persons with MS, compared to the non-exercise MS control group. PMID- 26992039 TI - A Biodesigned Nanocomposite Biomaterial for Auricular Cartilage Reconstruction. AB - Current biomaterials for auricular replacement are associated with high rates of infection and extrusion. The development of new auricular biomaterials that mimic the mechanical properties of native tissue and promote desirable cellular interactions may prevent implant failure. A porous 3D nanocomposite scaffold (NS) based on POSS-PCU (polyhedral oligomeric silsesquioxane nanocage into polycarbonate based urea-urethane) is developed with an elastic modulus similar to native ear. In vitro biological interactions on this NS reveal greater protein adsorption, increased fibroblast adhesion, proliferation, and collagen production compared with Medpor (the current synthetic auricular implant). In vivo, the POSS PCU with larger pores (NS2; 150-250 MUm) have greater tissue ingrowth (~5.8* and ~1.4 * increase) than the POSS-PCU with smaller pores (NS1; 100-50 MUm) and when compared to Medpor (>100 MUm). The NS2 with the larger pores demonstrates a reduced fibrotic encapsulation compared with NS1 and Medpor (~4.1* and ~1.6*, respectively; P < 0.05). Porosity also influences the amount of neovascularization within the implants, with no blood vessel observed in NS1 (12 weeks postimplantation). The lack of chronic inflammatory response for all materials may indicate that the elastic modulus and pore size of the implant scaffold could be important design considerations for influencing fibrotic responses to auricular and other soft tissue implants. PMID- 26992040 TI - Alpha-boswellic acid protects against ethanol-induced gastric injury in rats: involvement of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway. AB - OBJECTIVES: The purpose of this study was to assess the gastroprotective properties of alpha-boswellic acid (alpha-BA), a pentacyclic triterpene compound from extracts of Frankincense. METHODS: The gastroprotection of alpha-BA was assessed with ethanol-induced gastric lesions model, by histopathological assessment and measuring gastric juice acidity (pH), gastric wall mucus (GWM), prostaglandins E2 (PGE-2), membrane lipids peroxidation (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity and amount of nitric oxide (NO). The gastroprotective effects of alpha-BA through the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) anti-oxidative pathway were presented and measured by immunohistochemistry and Western blot. KEY FINDINGS: The results showed that alpha-BA reduced injuries associated with the administration of ethanol, gastric juice acidity and the formation of MDA and increased CAT activity and SOD activity and the level of NO and PGE-2 in a dose depended manner. The expression of both Nrf2 and HO-1 was significantly increased in the group treated with 200 mg/kg alpha-BA, which suggested that activation of the Nrf2/HO-1 pathway might be critical in alpha-BA's prevention of gastric ulcers. CONCLUSIONS: These findings demonstrate that alpha-BA decreases oxidative stress and that the Nrf2/HO-1 pathway might play a role in the gastroprotective action of alpha-BA in ethanol-induced gastric injury in rats. PMID- 26992041 TI - Effect of propranolol on survival in patients with decompensated cirrhosis: a nationwide study based Danish patient registers. AB - BACKGROUND & AIMS: We assessed the impact of propranolol on death, risk of hepatorenal syndrome and peritonitis in patients with cirrhosis. METHODS: This study was a retrospective observational study and data were retrieved from Danish databases. We used our own criteria to stratify the patients into groups of patients with mildly decompensated cirrhosis or severely decompensated cirrhosis. A subgroup of patients with a history of peritonitis was also analyzed. Follow-up time was limited to 2 years from cohort entry. The reported hazard ratios (HR) with 95% confidence interval (CI) were based on a propensity score matched cohort. RESULTS: Among 3719 patients, we found 3075 patients with mildly and 644 with severely decompensated cirrhosis. Propranolol was used by 20% of the patients. Among the patients with mildly decompensated cirrhosis, propranolol use vs. non-propranolol was related with a HR of 0.7 (95% CI 0.6-0.9) and among the patients with severely decompensated cirrhosis, the HR was 0.6 (95% CI 0.4-0.9). Reduced mortality was found for doses of propranolol lower than 160 mg/day only. Among 361 patients with peritonitis, we found reduced mortality in the propranolol group with a HR of 0.5 (95% CI 0.3-0.8). The use of propranolol was associated with a HR of 0.4 (95% CI 0.2-0.9) for developing peritonitis during follow-up among patients with severely decompensated cirrhosis. CONCLUSIONS: In patients with decompensated cirrhosis, we found an association between propranolol use and reduced mortality risk for doses lower than 160 mg/day. PMID- 26992042 TI - The effectiveness of bowel and bladder interventions in children with spina bifida. AB - AIM: Using the World Health Organization International Classification of Functioning, Disability and Health (ICF), the aim of this study was to identify effective strategies for managing urinary and bowel complications resulting from spina bifida. METHOD: Charts of 210 children between 4- and 13-years-old with spina bifida were reviewed to quantify medical interventions and continence status. Standardized quality of life (QOL) questionnaires were administered to a subset of participants; child and parent interviews were carried out to examine the experience of living with bowel and bladder incontinence. Practitioners were also interviewed to understand their perspectives of intervention effectiveness. RESULTS: Chart review indicated less than half of children were continent for bowel and bladder. More variability existed in bowel continence programs, and practitioners considered bowel continence more difficult to achieve than bladder continence. No significant associations were found between continence status and QOL measures. Interviews, however, reflected how managing continence at home and school more broadly affects QOL. Among practitioners, some focused primarily on optimizing physical health while others focused on activity and participation. INTERPRETATION: While continence is a goal, programs used to achieve this are individualized and outcomes may be affected by differential treatment effects, environmental factors, and/or stigma experienced by children. PMID- 26992043 TI - Controllable ROMP Tacticity by Harnessing the Fluxionality of Stereogenic-at Ruthenium Complexes. AB - Readily accessible and easy-to-handle Ru complexes capable of generating all-Z polynorbornene and polynorbornadiene by ring-opening metathesis polymerization (ROMP) with controllable selectivity, ranging from ~50 to >=95% syndiotactic, are introduced. It is demonstrated that the rate of non-metathesis based polytopal isomerization and levels of syndiotacticity may be fine-tuned by the adjustment of monomer concentration and catalyst's steric and electronic characteristics. PMID- 26992045 TI - An unprecedented benzannulation of oxindoles with enalcarbenoids: a regioselective approach to functionalized carbazoles. AB - A novel Rh(ii)/Bronsted acid catalyzed tandem benzannulation of oxindoles with enaldiazo carbonyls led to the formation of valuable 1-hydroxy-2-acylcarbazoles. This reaction is proposed to involve a formal insertion of a rhodium enalcarbenoid into an oxindole sp(2) C-O bond, an oxa-Michael addition, Friedel Crafts reaction and a semipinacol type 1,2-carbonyl migration. PMID- 26992044 TI - Botulinum Toxin as Monotherapy in Symptomatic Trigeminal Neuralgia. AB - BACKGROUND: Trigeminal neuralgia (TN) is one of the most agonizing facial pain disorders that humans endure. Studies on onabotulinum toxin A (BTX-A) treatment for TN are limited, but promising with respect to TN of no identifiable cause. We aimed to investigate the efficiency and safety of BTX-A treatment in a 60-year old male with diabetes mellitus who in March 2013 presented with TN caused by an exostosis in Meckel's cave. METHODS: The patient was medically treatment refractory due to insufficient pain relief and adverse events of hyperglycemia, and surgery was declined due to complex anatomy. As a last resort, BTX-A was injected into the pain trigger zones of the trigeminal nerve (V5). RESULTS: Complete analgesia was reported 2 weeks after BTX-A injection. Pain medications were discontinued and laboratory values returned to acceptable levels. Regular BTX-A treatment during the next 28 months showed sustained analgesic effect. CONCLUSIONS: BTX-A has an excellent safety profile and may be efficient for patients with symptomatic TN not suited for conventional therapies. PMID- 26992046 TI - In Vivo Interleukin-13-Primed Macrophages Contribute to Reduced Alloantigen Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants. AB - Transplantation of mesenchymal stem cells (MSCs) into injured or diseased tissue for the in situ delivery of a wide variety of MSC-secreted therapeutic proteins is an emerging approach for the modulation of the clinical course of several diseases and traumata. From an emergency point-of-view, allogeneic MSCs have numerous advantages over patient-specific autologous MSCs since "off-the-shelf" cell preparations could be readily available for instant therapeutic intervention following acute injury. Although we confirmed the in vitro immunomodulatory capacity of allogeneic MSCs on antigen-presenting cells with standard coculture experiments, allogeneic MSC grafts were irrevocably rejected by the host's immune system upon either intramuscular or intracerebral transplantation. In an attempt to modulate MSC allograft rejection in vivo, we transduced MSCs with an interleukin-13 (IL13)-expressing lentiviral vector. Our data clearly indicate that prolonged survival of IL13-expressing allogeneic MSC grafts in muscle tissue coincided with the induction of an alternatively activated macrophage phenotype in vivo and a reduced number of alloantigen-reactive IFNgamma- and/or IL2 producing CD8(+) T cells compared to nonmodified allografts. Similarly, intracerebral IL13-expressing MSC allografts also exhibited prolonged survival and induction of an alternatively activated macrophage phenotype, although a peripheral T cell component was absent. In summary, this study demonstrates that both innate and adaptive immune responses are effectively modulated in vivo by locally secreted IL13, ultimately resulting in prolonged MSC allograft survival in both muscle and brain tissue. Stem Cells 2016;34:1971-1984. PMID- 26992047 TI - Australian nurses' perceptions of the use of manual restraint in the Emergency Department: a qualitative perspective. AB - AIMS AND OBJECTIVES: To explore emergency nurses perceptions of the use of manual restraint. BACKGROUND: Manual restraint of patients has historically been an accepted practice, though little is known about the use of manual restraint in general hospitals. DESIGN: A qualitative, descriptive, exploratory, study was undertaken. METHOD: Fifteen semi-structured interviews with emergency nurses were completed. Data were analysed using qualitative thematic analysis procedures. RESULTS: The following themes were identified: 'part of the job', 'reasons for manual restraint', 'restraint techniques', 'consequences' and 'lack of documentation'. Manual restraint occurred frequently each shift and most were not documented. This may be due to nurse's perceptions that manually restraining a patient did not comprise formal restraint and was the only option. Nurses used manual restraint to manage patients who were violent and aggressive or to perform procedures. However, they reported a lack of education and training in manual restraint. Nurses identified several consequences for the patient, staff and the organisation as a result of these events including psychological and physical injuries. CONCLUSIONS: Empirical research of prevalence and issues surrounding manual restraint events is required to inform health care organisations and government to develop, implement and evaluate appropriate policies and strategies to ensure safety of patients and staff. The employment of peer support workers and professionals with expertise in mental health and dementia may aid in the reduction of manual restraint events and improve care of all patients within the Emergency Department. Research on manual restraint in health settings is also needed. RELEVANCE TO CLINICAL PRACTICE: Nurses need to be aware that manual restraint is not just an accepted part of their work, but is a strategy of last resort that should be documented. Organisations must implement standardised educational programmes for nurses together with policies and processes to monitor and evaluate manual restraint events. PMID- 26992048 TI - Nursing Taxonomies in Spain: Research Themes Presented at the AENTDE Conferences Over a 16-Year Period. AB - OBJECTIVE: To identify the types of studies of nursing taxonomies and priority research themes presented at AENTDE conferences between 1996 and 2012. METHOD: Four hundred oral communications and posters and 27 lectures presented at the AENTDE meetings were reviewed by means of a descriptive analysis of the types of studies conducted and a content analysis of priority research themes. RESULTS: The most commonly presented studies were descriptions of the implementation of nursing taxonomies, which accounted for 27.4% of the total over the 16-year period. However, their prevalence fell from 31.8% in 1996 to 9.1% in 2012. Basic research studies accounted for 17.4% of studies overall but were the most frequent in 2012, when their proportion had risen to 37.5%. CONCLUSION: The prevalence of basic research studies increased notably over the 16-year period. Content validity studies rose in number, while face validity studies fell. Studies of the practical implementation of taxonomies also declined. OBJETIVO: Identificar los tipos de estudios de taxonomias enfermeras y los temas de investigacion prioritarios presentados en las convenciones de AENTDE desde 1996 a 2012. METODO: Se revisaron 400 comunicaciones y 27 ponencias presentadas a 9 simposiums de AENTDE realizando un analisis del tipo de estudio y un analisis de contenido de los temas. RESULTADOS: Los estudios mas frecuentes son las experiencias de implantacion de las taxonomias enfermeras con un porcentaje medio de un 27.4% que partiendo de un 31.8% en 1996 disminuyo a un 9,1% en 2012. La investigacion basica tienen un porcentaje medio del 17.4% obteniendose el mayor porcentaje en 2012 con un 37,5%. CONCLUSION: La prevalencia de los estudios de investigacion basica se incremento notablemente durante el periodo de 16 anos. Los estudios de validez de contenido aumentaron en numero, mientras que los estudios de validez aparente cayeron. Los estudios sobre la aplicacion practica de las taxonomias tambien disminuyeron. PMID- 26992049 TI - Spontaneous Course of Biliary Sludge Over 12 Months in Dogs with Ultrasonographically Identified Biliary Sludge. AB - BACKGROUND: Biliary sludge is associated with gallbladder (GB) dysmotility and mucus hypersecretion suggesting a link between biliary sludge and the formation of GB mucoceles (GBM). If biliary sludge progresses to GBM, treatment to reduce the production and progression of sludge is warranted. HYPOTHESIS/OBJECTIVES: The objective of this study was to determine the course of biliary sludge in dogs. ANIMALS: Seventy-seven healthy, client-owned dogs >=4 years of age screened for biliary sludge; 45 affected dogs identified. METHODS: Prospective, observational design. Serial ultrasound examinations were evaluated at 3, 6, 9, and 12 months to monitor degree of sludge based on proportion of GB filled with sludge (mild [0.01-24.4%], moderate [24.5-49.4%], moderate to severe [49.5-74.4%], severe [74.5-100%]), gravity dependency of sludge, and GB dimensions. RESULTS: After 1 year of follow-up, the degree of sludge was mild (34%), moderate (47%), moderate to severe (13%), severe (3%), or absent (3%). There was no significant difference in median degree of sludge over 1 year (P = .36). There were no significant changes in the gravity dependency of sludge over 1 year. A subset of dogs, 24%, with initial gravity-dependent sludge developed a combination of nondependent and dependent sludge. Dogs had resolved (2%), decreased (19%), static (40%), increased (29%), or recurrent (10%) sludge at the conclusion of the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Biliary sludge was prevalent, affected dogs remained asymptomatic, and it rarely resolves in healthy dogs over a period of 1 year. Some dogs developed nongravity-dependent sludge within 1 year, which might indicate changes in consistency of sludge. PMID- 26992051 TI - Kinetic and kinematic gait analysis in the pelvic limbs of normal and post hemilaminectomy Dachshunds. AB - OBJECTIVE: To compare pelvic limb kinetic and kinematic gait parameters between Dachshunds six months following hemilaminectomy for treatment of thoracolumbar disc extrusion (post-hemilaminectomy; PHL) and Dachshunds without history and clinical evidence of spinal cord disease (control; CON). METHODS: The CON (n = 8) and PHL (n = 6) Dachshunds were recruited for objective gait evaluation. Kinetic data collected included peak vertical force (PVF), stance phase duration and swing phase duration. Kinematic data collected included tarsal, stifle and hip range of motion (ROM) during stance and swing phases of the trot, tail ROM, and horizontal and vertical components of pelvis ROM. RESULTS: No significant differences were identified between tarsal, stifle, hip, and tail ROM between CON and PHL Dachshunds. Although PVF was not significantly different between CON and PHL Dachshunds, PVF varied on average by 14% between the pelvic limbs in PHL Dachshunds (p <0.01). Horizontal and vertical components of pelvic ROM were on average 51% and 36% greater in PHL Dachshunds compared to CON Dachshunds (p = 0.04 and p = 0.02 respectively). CLINICAL SIGNIFICANCE: Six months after decompressive hemilaminectomy, Dachshunds have abnormal pelvic motion and asymmetric pelvic limb weight bearing. Pelvic sway (ROM) may be a more sensitive indicator of myelopathy than pelvic limb joint ROM and may serve as a useful objective tool to characterize response to treatment in patients with spinal cord disease. PMID- 26992050 TI - Polyphenol rich olive oils improve lipoprotein particle atherogenic ratios and subclasses profile: A randomized, crossover, controlled trial. AB - SCOPE: Lipoprotein particle measures performed by nuclear magnetic resonance (NMR), and associated ratios, may be better markers for atherosclerosis risk than conventional lipid measures. The effect of two functional olive oils, one enriched with its polyphenols (FVOO, 500 ppm), and the other (FVOOT) with them (250 ppm) and those of thyme (250 ppm), versus a standard virgin olive oil (VOO), on lipoprotein particle atherogenic ratios and subclasses profiles was assessed. METHODS AND RESULTS: In a randomized, double-blind, crossover, controlled trial, 33 hypercholesterolemic individuals received 25 mL/day of VOO, FVOO, and FVOOT. Intervention periods were of 3 weeks separated by 2-week washout periods. Lipoprotein particle counts and subclasses were measured by NMR. Polyphenols from olive oil and thyme modified the lipoprotein subclasses profile and decreased the total LDL particle/total HDL particle (HDL-P), small HDL/large HDL, and HDL cholesterol/HDL-P ratios, and decreased the lipoprotein insulin resistance index (LP-IR) (p < 0.05). CONCLUSION: Olive oil polyphenols, and those from thyme provided benefits on lipoprotein particle atherogenic ratios and subclasses profile distribution. Polyphenol-enriched olive oil is a way of increasing the olive oil healthy properties while consuming the same amount of fat, as well as a useful and complementary tool for the management of cardiovascular risk individuals. PMID- 26992052 TI - Tailoring of Polarizing Agents in the bTurea Series for Cross-Effect Dynamic Nuclear Polarization in Aqueous Media. AB - A series of 18 nitroxide biradicals derived from bTurea has been prepared, and their enhancement factors E ((1)H) in cross-effect dynamic nuclear polarization (CE DNP) NMR experiments at 9.4 and 14.1 T and 100 K in a DNP-optimized glycerol/water matrix ("DNP juice") have been studied. We observe that E ((1)H) is strongly correlated with the substituents on the polarizing agents, and its trend is discussed in terms of different molecular parameters: solubility, average e-e distance, relative orientation of the nitroxide moieties, and electron spin relaxation times. We show that too short an e-e distance or too long a T1e can dramatically limit E ((1)H). Our study also shows that the molecular structure of AMUPol is not optimal and its E ((1)H) could be further improved through stronger interaction with the glassy matrix and a better orientation of the TEMPO moieties. A new AMUPol derivative introduced here provides a better E ((1)H) than AMUPol itself (by a factor of ca. 1.2). PMID- 26992054 TI - Perceived incivility during emergency department phone consultations. AB - OBJECTIVE: Perceived incivility during ED medical phone consultations is poorly researched. We aimed to determine frequency and factors influencing perceived incivility during ED phone consultations. METHODS: We conducted a prospective self-reported survey of 40 consecutive phone consultations for 21 ED volunteer doctors. Consultations were classified based on the aim of consultation and deemed as 'positive', 'neutral' or 'negative' based on the perceptions of the consulting doctor. Training levels, time bands and specialty data were collected for both consulting and consulted parties. RESULTS: Fifty-seven of 714 included consultations (7.98%, 95% CI 6.2-10.2%) were reported as negative by ED medical staff. Factors associated with significant incidence of negative grading of consultation involved requests for investigations (19.3% vs 5.3%, P < 0.01), consultations with specialist trainees postgraduate year > 4 (9.1% vs 3.8%, P < 0.01) and those involving radiology specialty (18% vs 5.32%, P < 0.01). The risk was lower when the consulted professional was a specialist medical practitioner as compared to specialist trainee (4.1% vs 9.4%, P = 0.02). Multiple logistical modelling suggests that female (adjusted OR 2.4, 95% CI 1.1-5.2) medical staff are more likely to report perceived incivility during ED phone consultations. CONCLUSIONS: Perceived incivility occurs infrequently during ED phone consultations. ED female medical staff are at an increased risk of perceived incivility during phone consultations with non-ED medical professionals. Health organisations should actively pursue programmes to investigate the occurrence of incivility during healthcare consultations and implement programmes to mitigate the risk of developing a negative workplace culture. PMID- 26992053 TI - Iodide and iodate effects on the growth and fruit quality of strawberry. AB - BACKGROUND: Iodine deficiency is an environmental health problem affecting one third of the global population. An iodine biofortification hydroponic experiment was conducted to explore the iodide and iodate uptake characteristics of strawberry plants, to measure the dosage effects of iodine on plant growth and to evaluate the influence of I- or IO3- application on fruit quality. RESULTS: After biofortification, the iodine contents of the fresh strawberry fruits were 600 4000 ug kg-1 , covering the WHO dietary iodine allowance of 150 ug . day-1 for adults. The iodine uptake of the strawberry plants increased with increasing I- or IO3- concentration of the culture solution. At the same iodine concentration, the iodate uptakes of various plant organs under I- treatments were apparently more than those under IO3- treatments. Low-level exogenous iodine (I- <= 0.25 mg L-1 or IO3- <= 0.50 mg L-1 ) not only promoted plant growth and increased biomass per plant, but also improved fruit quality by enhancing the vitamin C and soluble sugar contents of the strawberry fruits. Nevertheless, excessive exogenous iodine inhibited plant growth and reduced biomass per plant. IO3- uptake apparently increased the total acidity and nitrate content of the fruits, reducing the quality of the strawberry fruits. Conversely, I- uptake obviously decreased the total acidity and nitrate content of the strawberry fruits, improving the fruit quality. CONCLUSION: The strawberry can be used as a target crop for iodine biofortification. Furthermore, applying an appropriate dose of KI can improve the fruit quality of the strawberry plants. (c) 2016 Society of Chemical Industry. PMID- 26992055 TI - The role of a cytosolic superoxide dismutase in barley-pathogen interactions. AB - Reactive oxygen species (ROS), including superoxide ( O2.-/ HO2.) and hydrogen peroxide (H2 O2 ), are differentially produced during resistance responses to biotrophic pathogens and during susceptible responses to necrotrophic and hemi biotrophic pathogens. Superoxide dismutase (SOD) is responsible for the catalysis of the dismutation of O2.-/ HO2. to H2 O2 , regulating the redox status of plant cells. Increased SOD activity has been correlated previously with resistance in barley to the hemi-biotrophic pathogen Pyrenophora teres f. teres (Ptt, the causal agent of the net form of net blotch disease), but the role of individual isoforms of SOD has not been studied. A cytosolic CuZnSOD, HvCSD1, was isolated from barley and characterized as being expressed in tissue from different developmental stages. HvCSD1 was up-regulated during the interaction with Ptt and to a greater extent during the resistance response. Net blotch disease symptoms and fungal growth were not as pronounced in transgenic HvCSD1 knockdown lines in a susceptible background (cv. Golden Promise), when compared with wild-type plants, suggesting that cytosolic O2.-/ HO2. contributes to the signalling required to induce a defence response to Ptt. There was no effect of HvCSD1 knockdown on infection by the hemi-biotrophic rice blast pathogen Magnaporthe oryzae or the biotrophic powdery mildew pathogen Blumeria graminis f. sp. hordei, but HvCSD1 also played a role in the regulation of lesion development by methyl viologen. Together, these results suggest that HvCSD1 could be important in the maintenance of the cytosolic redox status and in the differential regulation of responses to pathogens with different lifestyles. PMID- 26992056 TI - Different precore/core mutations of hepatitis B interact with, limit, or favor liver fibrosis severity. AB - BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (>=F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity. PMID- 26992057 TI - Obstetric anal sphincter injury and incontinence 15-23 years after vaginal delivery. AB - INTRODUCTION: The primary aim was to study prevalence of obstetric anal sphincter injuries (OASIS) after normal vaginal deliveries (NVD) and operative vaginal deliveries (OVD) with a subgroup analysis of forceps (FD) vs. vacuum deliveries (VD). The secondary aim was to study the association between OASIS and anal incontinence 15-23 years later. MATERIAL AND METHODS: This was a cross-sectional study including 8137 primiparous women in Trondheim, Norway, from 1990 to 1997. The outcome measure was the adjusted odds ratio (aOR) for OASIS between delivery groups. A total of 1122 women responded to a postal questionnaire containing the Colorectal-Anal Distress Inventory (CRADI) in 2013. The aOR for anal incontinence and the difference in CRADI score between women with and without OASIS were calculated. RESULTS: OASIS prevalence was 2% for NVD and 10% for OVD (10% FD, 9% VD). aOR for OASIS was 5.01 (95%CI 3.85-6.51) comparing OVD with NVD. There was no difference between FD and VD (aOR 1.15, 95% CI 0.79-1.67). FD was associated with higher risk of fourth degree perineal tear than VD (aOR 5.08, 95% CI 1.47 17.49). OASIS was associated with increased risk of leakage of well-formed (aOR 8.61, 95% CI 3.08-24.12) and loose stool (aOR 2.75, 95% CI 1.43-5.27) and higher CRADI score (Mann-Whitney U-test, p = 0.01). CONCLUSIONS: OVD was associated with increased risk of OASIS. FD was associated with higher risk of fourth degree perineal tear compared with VD. OASIS was associated with increased risk of anal incontinence and higher CRADI score 15-23 years later. PMID- 26992058 TI - Kynurenine Modulates MMP-1 and Type-I Collagen Expression Via Aryl Hydrocarbon Receptor Activation in Dermal Fibroblasts. AB - Dermal fibrosis is characterized by a high deposition of extracellular matrix (ECM) and tissue cellularity. Unfortunately all means of treating this condition are unsatisfactory. We have previously reported the anti-fibrotic effects of Kynurenine (Kyn), a tryptophan metabolite, in fibrotic rabbit ear model. Here, we report the mechanism by which Kyn modulates the expression of key ECM components in dermal fibroblasts. The results showed that Kyn activates aryl hydrocarbon receptor (AHR) nuclear translocation and up-regulates cytochrome-P450 (CYP1A-1) expression, the AHR target gene. A specific AHR antagonist, 6,2',4' trimethoxyflavone, inhibited the Kyn-dependent modulation of CYP1A-1, MMP-1, and type-I collagen expression. Establishing the anti-fibrogenic effect of Kyn and its mechanism of action, we then developed nano-fibrous Kyn slow-releasing dressings and examined their anti-fibrotic efficacy in vitro and in a rat model. Our results showed the feasibility of incorporating Kyn into PVA/PLGA nanofibers, prolonging the Kyn release up to 4 days tested. Application of medicated dressings significantly improved the dermal fibrosis indicated by MMP-1 induction, alpha-smooth muscle actin and type-I collagen suppression, and reduced tissue cellularity, T-cells and myofibroblasts. This study clarifies the mechanism by which Kyn modulates ECM expression and reports the development of a new slow-releasing anti-fibrogenic dressing. J. Cell. Physiol. 231: 2749-2760, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26992060 TI - 3D Printing of Conductive Complex Structures with In Situ Generation of Silver Nanoparticles. AB - Coupling the photoreduction of a metal precursor with 3D-printing technology is shown to allow the fabrication of conductive 3D hybrid structures consisting of metal nanoparticles and organic polymers shaped in complex multilayered architectures. 3D conductive structures are fabricated incorporating silver nitrate into a photocurable oligomer in the presence of suitable photoinitiators and exposing them to a digital light system. PMID- 26992061 TI - Computational SN 2-Type Mechanism for the Difluoromethylation of Lithium Enolate with Fluoroform through Bimetallic C-F Bond Dual Activation. AB - The reaction mechanism for difluoromethylation of lithium enolates with fluoroform was analyzed computationally (DFT calculations with the artificial force induced reaction (AFIR) method and solvation model based on density (SMD) solvation model (THF)), showing an SN 2-type carbon-carbon bond formation; the "bimetallic" lithium enolate and lithium trifluoromethyl carbenoid exert the C-F bond "dual" activation, in contrast to the monometallic butterfly-shaped carbenoid in the Simmons-Smith reaction. Lithium enolates, generated by the reaction of 2 equiv. of lithium hexamethyldisilazide (rather than 1 or 3 equiv.) with the cheap difluoromethylating species fluoroform, are the most useful alkali metal intermediates for the synthesis of pharmaceutically important alpha difluoromethylated carbonyl products. PMID- 26992059 TI - Morbidity and mortality of sickle cell disease patients starting intermittent haemodialysis: a comparative cohort study with non- Sickle dialysis patients. AB - We performed a retrospective study to assess the changes in clinical, biological and heart echocardiographic parameters in 32 sickle cell disease (SCD) patients beginning haemodialysis. Acute SCD-related complications were similar at 6 months before and 6 months after the initiation of haemodialysis. Median haemoglobin level did not change significantly, but the need for blood transfusions increased (P < 0.001). The 5-year incidence of death was higher in SCD patients (P < 0.0001). The 5-year likelihood of receiving a renal graft was lower in SCD patients (P = 0.022). Our findings suggest that SCD patients have poorer survival and a lower likelihood of receiving a renal graft. PMID- 26992062 TI - The effects of a recalled injustice on the experience of experimentally induced pain and anxiety in relation to just-world beliefs. AB - BACKGROUND: A growing field of investigation into social justice cognitions and pain suggests perceived injustice has a negative impact on pain, but little is known about individual variation in the impact of a perceived injustice. One published study found that individuals with a strong rather than a weak just world belief reported greater pain from the cold pressor task after experiencing a perceived injustice, but an overt measure of perceived unfairness is needed to investigate this relationship. METHODS: Following the completion of just-world belief and state anxiety scales, and the cold pressor task, 114 healthy participants were interviewed about either an experienced injustice or the characteristics of their home, before repeating the cold pressor task. Pain and anxiety measures were completed following each cold pressor task. RESULTS: Opposing the hypotheses, no differences were found on pain and anxiety between the two interview conditions, and individuals with a strong just-world belief did not report higher pain and anxiety levels following a recalled injustice. However, within the recalled injustice condition, unfairness ratings were associated with significantly increased pain and anxiety. CONCLUSIONS: Recalled personal injustice unrelated to one's current pain experience had a negative impact on pain and anxiety associated with the cold pressor task. These findings indicate that intervention development should be cognizant of the role of everyday injustices and not just those related to pain, on the pain experience. WHAT DOES THIS STUDY ADD?: This study shows that, independent of just-world beliefs, perceived unfairness associated with a recalled injustice unrelated to pain has a negative impact on the experience of acute pain. PMID- 26992063 TI - Nanostructures from Synthetic Genetic Polymers. AB - Nanoscale objects of increasing complexity can be constructed from DNA or RNA. However, the scope of potential applications could be enhanced by expanding beyond the moderate chemical diversity of natural nucleic acids. Here, we explore the construction of nano-objects made entirely from alternative building blocks: synthetic genetic polymers not found in nature, also called xeno nucleic acids (XNAs). Specifically, we describe assembly of 70 kDa tetrahedra elaborated in four different XNA chemistries (2'-fluro-2'-deoxy-ribofuranose nucleic acid (2'F RNA), 2'-fluoroarabino nucleic acids (FANA), hexitol nucleic acids (HNA), and cyclohexene nucleic acids (CeNA)), as well as mixed designs, and a ~600 kDa all FANA octahedron, visualised by electron microscopy. Our results extend the chemical scope for programmable nanostructure assembly, with implications for the design of nano-objects and materials with an expanded range of structural and physicochemical properties, including enhanced biostability. PMID- 26992064 TI - Mechanical Ventilation and Diaphragmatic Atrophy in Critically Ill Patients: An Ultrasound Study. AB - OBJECTIVE: Mechanical ventilation contributes to diaphragmatic atrophy and dysfunction, and few techniques exist to assess diaphragmatic function: the purpose of this study was to quantify diaphragm atrophy in a population of critically ill mechanically ventilated patients with ultrasound and to identify risk factors that can worsen diaphragmatic activity. DESIGN: Prospective observational study. SETTING: ICU of a 1,200-bed university hospital. PATIENTS: Newly intubated adult critically ill patients. INTERVENTIONS: Diaphragm thickness in the zone of apposition was measured daily with ultrasound, from the first day of mechanical ventilation till discharge to the main ward. MEASUREMENTS AND MAIN RESULTS: Daily atrophy rate (DeltaTdi/d) was calculated as the reduction in percentage from the previous measurement. To analyze the difference in atrophy rate (DeltaTdi/d), ventilation was categorized into four classes: spontaneous breathing or continuous positive airway pressure; pressure support ventilation 5 12 cm H2O (low pressure support ventilation); pressure support ventilation greater than 12 cm H2O (high pressure support ventilation); and controlled mechanical ventilation. Multivariate analysis with ventilation support and other clinical variables was performed to identify risk factors for atrophy. Forty patients underwent a total of 153 ultrasonographic evaluations. Mean (SD) DeltaTdi/d was -7.5% (12.3) during controlled mechanical ventilation, -5.3% (12.9) at high pressure support ventilation, -1.5% (10.9) at low pressure support ventilation, +2.3% (9.5) during spontaneous breathing or continuous positive airway pressure. At multivariate analysis, only the ventilation support was predictive of diaphragm atrophy rate. Pressure support predicted diaphragm thickness with coefficient -0.006 (95% CI, -0.010 to -0.002; p = 0.006). CONCLUSIONS: In critically ill mechanically ventilated patients, there is a linear relationship between ventilator support and diaphragmatic atrophy rate. PMID- 26992065 TI - Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor. AB - OBJECTIVES: Angiotensin-converting enzyme inhibitors are associated with deleterious hypotension during anesthesia and shock. Because the pharmacologic effects of angiotensin-converting enzyme inhibitors are partly mediated by increased bradykinin B2 receptor activation, this study aimed to determine the impact of acute B2 receptor blockade during hemorrhagic shock in angiotensin converting enzyme inhibitor-treated mice. DESIGN: In vivo study. SETTING: University research unit. SUBJECTS: C57/Bl6 mice. INTERVENTIONS: The hemodynamic effect of B2 receptor blockade using icatibant (B2 receptor antagonist) was studied using a pressure-targeted hemorrhagic shock and a volume-targeted hemorrhagic shock. Animals were anesthetized with ketamine and xylazine (250 mg/kg and 10 mg/kg, respectively), intubated using intratracheal cannula, and ventilated (9 mL/kg, 150 min). Five groups were studied: 1) sham-operated animals, 2) control shocked mice, 3) shocked mice treated with ramipril for 7 days (angiotensin-converting enzyme inhibitors) before hemorrhagic shock, 4) shocked mice treated with angiotensin-converting enzyme inhibitors and a single bolus of icatibant (HOE-140) immediately before anesthesia (angiotensin converting enzyme inhibitors + icatibant), and 5) shocked mice treated with a single bolus of icatibant. One hour after volume-targeted hemorrhagic shock, blood lactate was measured to evaluate organ failure. MEASUREMENTS AND MAIN RESULTS: During pressure-targeted hemorrhagic shock, the mean blood volume withdrawn was significantly lower in the angiotensin-converting enzyme inhibitor group than in the other groups (p < 0.001). During volume-targeted hemorrhagic shock, icatibant prevented blood pressure lowering in the angiotensin-converting enzyme inhibitor group (p < 0.001). Blood lactate was significantly higher in the angiotensin-converting enzyme inhibitor group than in the other groups, particularly the HOE groups. CONCLUSIONS: During hemorrhagic shock, acute B2 receptor blockade significantly attenuates the deleterious hemodynamic effect of angiotensin-converting enzyme inhibitor treatment in mice. This beneficial effect of B2 receptor blockade is rapidly reached and sustained with a single bolus of icatibant. This benefit could be of interest in angiotensin-converting enzyme inhibitor-treated patients during both emergency anesthesia and resuscitation. PMID- 26992066 TI - Long-Term Quality of Life Among Survivors of Severe Sepsis: Analyses of Two International Trials. AB - OBJECTIVES: To describe the quality of life among sepsis survivors. DESIGN: Secondary analyses of two international, randomized clinical trials (A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis [derivation cohort] and PROWESS-SHOCK [validation cohort]). SETTING: ICUs in North and South America, Europe, Africa, Asia, and Australia. PATIENTS: Adults with severe sepsis. We analyzed only patients who were functional and living at home without help before sepsis hospitalization (n = 1,143 and 987 from A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis and PROWESS SHOCK, respectively). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis and PROWESS-SHOCK, the average age of patients living at home independently was 63 and 61 years; 400 (34.9%) and 298 (30.2%) died by 6 months. In A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis, 580 patients had a quality of life measured using EQ-5D at 6 months. Of these, 41.6% could not live independently (22.7% were home but required help, 5.1% were in nursing home or rehabilitation facilities, and 5.3% were in acute care hospitals). Poor quality of life at 6 months, as evidenced by problems in mobility, usual activities, and self-care domains were reported in 37.4%, 43.7%, and 20.5%, respectively, and the high incidence of poor quality of life was also seen in patients in PROWESS-SHOCK. Over 45% of patients with mobility and self-care problems at 6 months in A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis died or reported persistent problems at 1 year. CONCLUSIONS: Among individuals enrolled in a clinical trial who lived independently prior to severe sepsis, one third had died and of those who survived, a further one third had not returned to independent living by 6 months. Both mortality and quality of life should be considered when designing new interventions and considering endpoints for sepsis trials. PMID- 26992067 TI - Outcome Measurement in ICU Survivorship Research From 1970 to 2013: A Scoping Review of 425 Publications. AB - OBJECTIVES: To evaluate the study designs and measurement instruments used to assess physical, cognitive, mental health, and quality of life outcomes of survivors of critical illness over more than 40 years old as a first step toward developing a core outcome set of measures for future trials to improve outcomes in ICU survivors. DESIGN: Scoping review. SETTING: Published articles that included greater than or equal to one postdischarge measure of a physical, cognitive, mental health, or quality of life outcome in more than or equal to 20 survivors of critical illness published between 1970 and 2013. Instruments were classified using the World Health Organization's International Classification of Functioning, Disability, and Health framework. SUBJECTS: ICU survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed 15,464 abstracts, and identified 425 eligible articles, including 31 randomized trials (7%), 116 cross-sectional studies (27%), and 278 cohort studies (65%). Cohort studies had a median (interquartile range) sample size of 96 survivors (52-209), with 38% not fully reporting loss to follow-up. A total of 250 different measurement instruments were used in these 425 articles. Among eligible articles, 25 measured physical activity limitations (6%), 40 measured cognitive activity limitations (9%), 114 measured mental health impairment (27%), 196 measured participation restriction (46%), and 276 measured quality of life (65%). CONCLUSIONS: Peer reviewed publications reporting patient outcomes after hospital discharge for ICU survivors have grown from 3 in the 1970s to more than 300 since 2000. Although there is evidence of consolidation in the instruments used for measuring participation restriction and quality of life, the ability to compare results across studies remains impaired by the 250 different instruments used. Most articles described cohort studies of modest size with a single follow-up assessment using patient-reported measures of participation restriction and quality of life. Development of a core outcome set of valid, reliable, and feasible measures is essential to improving the outcomes of critical illness survivors. PMID- 26992069 TI - Histologically benign, clinically aggressive: Progressive non-optic pathway pilocytic astrocytomas in adults with NF1. AB - Although optic pathway gliomas are the most common brain tumors associated with neurofibromatosis type 1 (NF1), extra-optic gliomas occur and may behave more aggressively with outcomes that differ by age. A retrospective case-control study was designed to describe the clinical course of adult NF1 patients with progressive extra-optic pilocytic astrocytomas (PAs) and compare to a pediatric cohort. Data for patients treated at the Johns Hopkins Comprehensive Neurofibromatosis Center from 2003 to 2013 were reviewed to identify cases (adults, age >18) and controls (pediatric, age <18) with clinically or radiographically progressive extra-optic PAs. Demographic, clinical, histologic, and radiographic data were collected. Three adult NF1 cases and four pediatric NF1 controls were identified. Mean age was 32.3 +/- 9.5 years, 66% male (cases); 12.8 +/- 4.2 years, 100% male (controls). Symptomatic progression occurred in two of-three adults (67%) while the majority of pediatric patients presented with isolated radiographic progression (n = 3, 75%). Onset tended to be more rapid in adults (4 +/- 1 vs. 14 +/- 8.3 months, P = 0.10). Subtotal resection was the treatment for all pediatric patients. Radiotherapy (n = 2), chemotherapy (n = 2), and targeted, biologic agents (n = 2) were administered in adults. Although all pediatric patients are living, outcomes were universally poor in adults with progression to death in all (median survival 17.1 months, range 6.6-30.3). In conclusion, despite grade I histology, all three adult NF1 patients with progressive extra-optic PAs suffered an aggressive clinical course which was not seen in pediatric patients. Clinicians should be aware of this clinico-histologic discrepancy when counseling and managing adult NF1 patients with progressive extra-optic PAs. (c) 2016 Wiley Periodicals, Inc. PMID- 26992068 TI - Using Supervised Machine Learning to Classify Real Alerts and Artifact in Online Multisignal Vital Sign Monitoring Data. AB - OBJECTIVE: The use of machine-learning algorithms to classify alerts as real or artifacts in online noninvasive vital sign data streams to reduce alarm fatigue and missed true instability. DESIGN: Observational cohort study. SETTING: Twenty four-bed trauma step-down unit. PATIENTS: Two thousand one hundred fifty-three patients. INTERVENTION: Noninvasive vital sign monitoring data (heart rate, respiratory rate, peripheral oximetry) recorded on all admissions at 1/20 Hz, and noninvasive blood pressure less frequently, and partitioned data into training/validation (294 admissions; 22,980 monitoring hours) and test sets (2,057 admissions; 156,177 monitoring hours). Alerts were vital sign deviations beyond stability thresholds. A four-member expert committee annotated a subset of alerts (576 in training/validation set, 397 in test set) as real or artifact selected by active learning, upon which we trained machine-learning algorithms. The best model was evaluated on test set alerts to enact online alert classification over time. MEASUREMENTS AND MAIN RESULTS: The Random Forest model discriminated between real and artifact as the alerts evolved online in the test set with area under the curve performance of 0.79 (95% CI, 0.67-0.93) for peripheral oximetry at the instant the vital sign first crossed threshold and increased to 0.87 (95% CI, 0.71-0.95) at 3 minutes into the alerting period. Blood pressure area under the curve started at 0.77 (95% CI, 0.64-0.95) and increased to 0.87 (95% CI, 0.71-0.98), whereas respiratory rate area under the curve started at 0.85 (95% CI, 0.77-0.95) and increased to 0.97 (95% CI, 0.94 1.00). Heart rate alerts were too few for model development. CONCLUSIONS: Machine learning models can discern clinically relevant peripheral oximetry, blood pressure, and respiratory rate alerts from artifacts in an online monitoring dataset (area under the curve > 0.87). PMID- 26992070 TI - High-sensitivity HLA class I peptidome analysis enables a precise definition of peptide motifs and the identification of peptides from cell lines and patients' sera. AB - The characterization of peptides bound to human leukocyte antigen (HLA) class I is of fundamental importance for understanding CD8+ T cell-driven immunological processes and for the development of immunomodulatory therapeutic strategies. However, until now, the mass spectrometric analysis of HLA-bound peptides has typically required billions of cells, still resulting in relatively few high confidence peptide identifications. Capitalizing on the recent developments in mass spectrometry and bioinformatics, we have implemented a methodology for the efficient recovery of acid-eluted HLA peptides after purification with the pan reactive antibody W6/32 and have identified a total of 27 862 unique peptides with high confidence (1% false discovery rate) from five human cancer cell lines. More than 93% of the identified peptides were eight to 11 amino acids in length and contained signatures that were in excellent agreement with published HLA binding motifs. Furthermore, by purifying soluble HLA class I complexes (sHLA) from sera of melanoma patients, up to 972 high-confidence peptides could be identified, including melanoma-associated antigens already described in the literature. Knowledge of the HLA class I peptidome should facilitate multiplex tetramer technology-based characterization of T cells, and allow the development of patient selection, stratification and immunomodulatory therapeutic strategies. PMID- 26992071 TI - In situ non-destructive measurement of biofilm thickness and topology in an interferometric optical microscope. AB - Biofilms are ubiquitous and impact the environment, human health, dental hygiene, and a wide range of industrial processes. Biofilms are difficult to characterize when fully hydrated, especially in a non-destructive manner, because of their soft structure and water-like bulk properties. Herein a method of measuring and monitoring the thickness and topology of live biofilms of using white light interferometry is described. Using this technique, surface morphology, surface roughness, and biofilm thickness were measured over time without while the biofilm continued to grow. The thickness and surface topology of a P. putida biofilm were monitored growing from initial colonization to a mature biofilm. Measured thickness followed expected trends for bacterial growth. Surface roughness also increased over time and was a leading indicator of biofilm growth. PMID- 26992072 TI - Primary mediastinal synovial sarcoma with subsequent development of primary adenoid cystic carcinoma of lung presenting as superior vena cava syndrome. AB - Primary mediastinal sarcomas are aggressive tumors with a very rare incidence. This report describes the case of a 35 year old male patient who presented with acute symptoms of dyspnoea, facial puffiness, engorged neck veins and hoarseness of voice. With the clinical picture consistent with the superior vena caval (SVC) syndrome, the patient was investigated with computed tomography of the chest. This revealed a large soft tissue density mass lesion compressing the SVC along with other critical superior mediastinal structures. Histopathological evaluation of the mass revealed features consistent with a soft tissue sarcoma and positive staining was observed for vimentin and S-100. Cytogenetic analysis by fluorescent in-situ hybridization (FISH) demonstrated the t(X: 18) translocation. Thus diagnosis was established as primary mediastinal synovial sarcoma. Patient was treated with three-cycles of neo-adjuvant (ifosfamide 2400mg/m2 on days 1-5 and doxorubicin 37.5 mg/m2 on days 1 & 2) chemotherapy, to which there was a partial response as per the RECIST criteria. Surgical excision of the mediastinal mass was performed, and further post-operative treatment with adjuvant chemo radiotherapy was provided. Patient was under regular surveillance at our clinic and remains free of symptoms one-year after treatment completion. But after 14 months of treatment completion patient again had symptoms of progressive dyspnea, hoareness of voice and mild facial puffiness over a period of 2 months. On further investigating he was found to have right-sided centrally located mass with cystic and necrotic changes with extension and compression of trachea, SVC, right upper lobe bronchus and its branches. Histopathological examination of the biopsy from the lesion revealed adenoid cystic carcinoma of the lung. Rest of the metastatic work up was within normal. Immunohistochemistry of the specimen revealed c-Kit positivity. In view of the morbid second surgery he was put on Imatinib 400mg once a day and celecoxib 200mg twice a day. After 4 months patient had partial response and presently continuing with the same regimen. Extensive literature search didn't reveal much information on combined primary mediastinal sarcoma and adenoid cystic carcinoma of lung. PMID- 26992073 TI - Worsening of calcinosis cutis with teriparatide treatment in two osteoporotic patients. AB - We present two cases of patients with systemic autoimmune diseases (one with dermatomyositis and one with CREST syndrome) who presented with a worsening of calcinosis cutis after treatment of osteoporosis with teriparatide. To our knowledge, this association is not described in the literature and might be considered in the spectrum of adverse reactions to teriparatide. PMID- 26992074 TI - Teaching hospital cataract surgical outcomes in Adelaide, Australia: response. PMID- 26992076 TI - Impact of oral clinical problems on oral health-related quality of life in brazilian children: a hierarchical approach. AB - BACKGROUND: Oral health-related quality of life may be influenced by a series of characteristics. Considering the multidimensional character of quality of life, these impacts should be evaluated in the context of the physical, psychological, and social domains. AIM: To evaluate the impact of clinical and perceived oral health problems on oral health-related quality of life in its different domains. DESIGN: Clinical exams were conducted on a representative cross-sectional sample of 12-year-old children in Brazil. The instrument Oral Impacts on Daily Performance (OIDP) was used to evaluate the quality of life in relation to oral health. Descriptive, bivariate, and multiple hierarchical analyses were conducted. RESULTS: Of the 7328 children studied, 2577 (33.5%) presented oral health-related impacts on quality of life. Clinical and perceived conditions of oral health were associated with the presence of overall impacts in the physical, psychological, and social dimensions of oral health-related quality of life. Furthermore, Family income was associated with overall impacts and the level of motivation to use dental health services was associated with the physical dimension. CONCLUSIONS: The clinical and perceived conditions of oral health in Brazilian 12-year-olds were associated with a negative impact on oral health related quality of life. PMID- 26992075 TI - Influence of Uptake Pathways on the Stereoselective Dissipation of Chiral Neonicotinoid Sulfoxaflor in Greenhouse Vegetables. AB - Stereoselectivity is of vital importance in our environment and needs to be taken into account for comprehensive risk assessment and regulatory decisions of chiral neonicotinoid sulfoxaflor. However, little is known about the dissipation of sulfoxaflor stereoisomers with respect to stereoselectivity in plants under greenhouse cultivation. To bridge the knowledge gap, the current study was initiated to investigate the stereoselective degradation of sulfoxaflor in solar greenhouse cucumber and tomato from foliage and root uptake pathways. The stereoselective dissipation of sulfoxaflor was not statistically different between enantiomer pairs from foliage and root pathways of vegetables (P < 0.05). The persistence of sulfoxaflor stereoisomers was consistently prolonged under the foliage uptake pathway (t1/2, 3.38-14.09 days) compared to the root uptake pathway (t1/2, 2.65-5.07 days) in both vegetable fruits. Nevertheless, the concentrations of (+)-sulfoxaflor A and (-)-sulfoxaflor B were both slightly higher than that of their antipode. The tiny difference should be emphasized because it might be magnified to a significant difference by the high-potential bioaccumulation of sulfoxaflor in the food chain. PMID- 26992077 TI - In situ and ex situ functionalization of nanostructured gallium oxy-hydroxide with a porphyrin dye. AB - The surface attachment of a porphyrin dye to nanocrystalline GaOOH was performed using two routes of solution-based functionalization. The first method of functionalization utilized an in situ incorporation of dissolved porphyrin salt in solution during the microwave synthesis step. Additionally, synthesized GaOOH nanorods were mixed in porphyrin solution after the microwave process to make an ex situ GaOOH/TTP-PO-3 . X-ray photoelectron spectroscopy confirmed the presence of expected surface species and provided evidence of increased surface coverage of TTP-PO3 on GaOOH in the ex situ- GaOOH/TTP-PO3 as compared to the in situ one. Size and morphology changes were investigated using SEM and, along with analysis of XRD, the in situ samples showed larger crystallite sizes. This was confirmed with PL due to the higher bandgap energy evident in the ex situ GaOOH/TTP-PO3 compared to the in situ sample. A stability study was performed using fluorescence spectroscopy which indicated no leaching of porphyrin from the in situ GaOOH/TTP-PO3 . However, porphyrin leaching was evident from the ex situ GaOOH/TTP-PO3 sample. The stability of the in situ GaOOH/TTP-PO3 makes it attractive for a number of interfacial applications. SCANNING 38:671-683, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26992079 TI - Stability-indicating chromatographic methods for determination of flecainide acetate in the presence of its degradation products; isolation and identification of two of its impurities. AB - In this work, two stability-indicating chromatographic methods have been developed and validated for determination of flecainide acetate (an antiarrhythmic drug) in the presence of its degradation products (flecainide impurities; B and D). Flecainide acetate was subjected to a stress stability study including acid, alkali, oxidative, photolytic and thermal degradation. The suggested chromatographic methods included the use of thin layer chromatography (TLC-densitometry) and high-performance liquid chromatography (HPLC). The TLC method employed aluminum TLC plates precoated with silica gel G.F254 as the stationary phase and methanol-ethyl acetate-33% ammonia (3:7:0.3, by volume) as the mobile phase. The chromatograms were scanned at 290 nm and visualized in daylight by the aid of iodine vapor. The developed HPLC method used a RP-C18 column with isocratic elution. Separation was achieved using a mobile phase composed of phosphate buffer pH 3.3-acetonitrile-triethylamine (53:47:0.03, by volume) at a flow rate of 1.0 mL/min and UV detection at 292 nm. Factors affecting the efficiency of HPLC method have been studied carefully to reach the optimum conditions for separation. The developed methods were validated according to the International Conference on Harmonization guidelines and were applied for bulk powder and dosage form. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26992080 TI - Mapping of a Novel Race Specific Resistance Gene to Phytophthora Root Rot of Pepper (Capsicum annuum) Using Bulked Segregant Analysis Combined with Specific Length Amplified Fragment Sequencing Strategy. AB - Phytophthora root rot caused by Phytophthora capsici (P. capsici) is a serious limitation to pepper production in Southern China, with high temperature and humidity. Mapping PRR resistance genes can provide linked DNA markers for breeding PRR resistant varieties by molecular marker-assisted selection (MAS). Two BC1 populations and an F2 population derived from a cross between P. capsici resistant accession, Criollo de Morelos 334 (CM334) and P. capsici-susceptible accession, New Mexico Capsicum Accession 10399 (NMCA10399) were used to investigate the genetic characteristics of PRR resistance. PRR resistance to isolate Byl4 (race 3) was controlled by a single dominant gene, PhR10, that was mapped to an interval of 16.39Mb at the end of the long arm of chromosome 10. Integration of bulked segregant analysis (BSA) and Specific Length Amplified Fragment sequencing (SLAF-seq) provided an efficient genetic mapping strategy. Ten polymorphic Simple Sequence Repeat (SSR) markers were found within this region and used to screen the genotypes of 636 BC1 plants, delimiting PhR10 to a 2.57 Mb interval between markers P52-11-21 (1.5 cM away) and P52-11-41 (1.1 cM). A total of 163 genes were annotated within this region and 31 were predicted to be associated with disease resistance. PhR10 is a novel race specific gene for PRR, and this paper describes linked SSR markers suitable for marker-assisted selection of PRR resistant varieties, also laying a foundation for cloning the resistance gene. PMID- 26992082 TI - Prognostic model to predict survival in patients with metastatic upper tract urothelial carcinoma treated with cisplatin-based chemotherapy. AB - OBJECTIVES: To create a novel prognostic model to predict survival in metastatic upper tract urothelial carcinoma patients treated with cisplatin-based chemotherapy. METHODS: After institutional review board approval, patients who had metastatic upper tract urothelial carcinoma and were treated with cisplatin based chemotherapy from 2000 to 2012 at Kaohsiung Chang Gung Memorial Hospital were retrospectively reviewed. Significantly predictive factors were identified by multivariate Cox regress analyses. Kaplan-Meier curves were plotted to estimate overall survival. Several prognostic models were validated by using our cohort, and Harrell's c-index was calculated to evaluate their predicting performances. RESULTS: The present study consisted of 136 patients with a median age of 62 years and a median follow-up visit of 13.6 months. Multivariate analyses showed that renal function, performance status, liver metastasis and number of metastatic sites was independently related to survival. Based on these four variables, we constructed a prognostic model "renal function, performance status, liver metastasis, number of metastatic sites" with significantly different survival (P < 0.001). C-index results were renal function, performance status, liver metastasis, number of metastatic sites model 0.80 (0.69-0.90), Bajorin model 0.72 (0.61-0.83), Taguchi model 0.77 (0.67-0.87) and Tanaka model 0.78 (0.69-0.88). Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model achieved the highest c-index in this study. CONCLUSIONS: Our renal function, performance status, liver metastasis, number of metastatic sites prognostic model could be useful for providing prognostic information on survival in patients with metastatic upper tract urothelial carcinoma. PMID- 26992078 TI - The specification and wiring of mammalian cutaneous low-threshold mechanoreceptors. AB - The mammalian cutaneous low-threshold mechanoreceptors (LTMRs) are a diverse set of primary somatosensory neurons that function to sense external mechanical force. Generally, LTMRs are composed of Abeta-LTMRs, Adelta-LTMRs, and C-LTMRs, which have distinct molecular, physiological, anatomical, and functional features. The specification and wiring of each type of mammalian cutaneous LTMRs is established during development by the interplay of transcription factors with trophic factor signalling. In this review, we summarize the cohort of extrinsic and intrinsic factors generating the complex mammalian cutaneous LTMR circuits that mediate our tactile sensations and behaviors. For further resources related to this article, please visit the WIREs website. PMID- 26992083 TI - An independent replication of the Adolescent-Community Reinforcement Approach with justice-involved youth. AB - BACKGROUND AND OBJECTIVES: Substance use disorders among youth remain a serious public health problem. Although research has overwhelmingly supported the use of evidenced-based interventions, one of the primary limitations of the current evidence base is that for the vast majority of treatments, the developers of the treatments are also the ones conducting research on them, raising the possibility of allegiance bias. METHODS: The present study was an independently conducted randomized controlled trial (n = 126) comparing an evidenced-based treatment for adolescent substance use, Adolescent-Community Reinforcement Approach (A-CRA), and assertive continuing care (ACC), to services as usual (SAU) provided by a juvenile probation department. Latent growth curve modeling was used to compare the treatments on change in substance use assessed by the Global Appraisal of Individual Needs (GAIN) at baseline and 3, 6, and 12 months following treatment entry. RESULTS: All youth evidenced a substantial reduction in substance use frequency and substance-related problems following treatment; however, youth treated with A-CRA/ACC evidenced a substantially greater decrease in substance related problems. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Results are consistent with studies conducted by A-CRA/ACC model developers supporting the effectiveness of the clinical approach and, because the outcomes resulted from an independent replication, are encouraging for the transportation potential of A-CRA/ACC. PMID- 26992084 TI - Work participation for people with severe mental illnesses: An integrative review of factors impacting job tenure. AB - BACKGROUND: Enabling people with severe mental illness to sustain employment remains a challenge. This is despite most wishing to be employed, and the development of effective vocational interventions and employment supports for this population. To better understand how to enable their sustained involvement in the workforce, this review sought to identify, analyse and summarise studies investigating the factors that impact the job tenure of workers with severe mental illness, irrespective of the type of employment support they received. METHODS: An integrative literature review approach was employed to locate, appraise and synthesise quantitative and qualitative research focused on job tenure published in the 20 years up to 2013. Findings from nineteen studies were extracted and integrated using thematic analytic strategies. RESULTS: Job tenure was mostly conceptualised across the reviewed studies as time spent in individual jobs rather than as ongoing participation in the workforce. Three themes describe the factors contributing to job tenure: (1) the worker's experience of doing the current job; (2) natural supports in the workplace; and (3) strategies for integrating work, recovery and wellness, each of which could either support or impede ongoing employment. CONCLUSION: Occupational therapists, other vocational specialists and mental health staff can use these factors as a guide to supporting people with severe mental illness in employment. More detailed examination of job tenure is required in future research not only on job duration but also on the quality of jobs held, their value for career development and the role of services in supporting tenure. PMID- 26992085 TI - Sustainable Chiral Polyamides with High Melting Temperature via Enhanced Anionic Polymerization of a Menthone-Derived Lactam. AB - Polyamides are very important polymers that find applications from commodities up to the automotive and biomedical sectors, and their impact is continuously growing. The synthesis of structurally significant, chiral, and sustainable polyamides is described via a new, convenient, and solvent-free anionic polymerization of a biobased epsilon-lactam, which is obtained from the renewable terpenoid ketone l-menthone in a one-step synthesis. These polyamides are shown to have outstanding structural and thermal properties, which are thus introduced via the structure and chirality of the natural lactam monomer and which are discussed and compared with those of petroleum-based, established, and commercial polyamide Nylon-6. X-ray data reveal a remarkable degree of crystallinity in these green polymers and emphasize the impact of their structural features on the resulting properties. PMID- 26992086 TI - Prosthetic Valve Endocarditis Following Dental Extractions. AB - Early-onset prosthetic valve endocarditis is a serious complication of valve replacement. We present two cases of early-onset prosthetic valve endocarditis caused by species of the anaerobic organism Prevotella, and discuss the issue of dental extraction prior to valve surgery. doi: 10.1111/jocs.12732 (J Card Surg 2016;31:321-323). PMID- 26992081 TI - Membrane-mediated regulation of vascular identity. AB - Vascular diseases span diverse pathology, but frequently arise from aberrant signaling attributed to specific membrane-associated molecules, particularly the Eph-ephrin family. Originally recognized as markers of embryonic vessel identity, Eph receptors and their membrane-associated ligands, ephrins, are now known to have a range of vital functions in vascular physiology. Interactions of Ephs with ephrins at cell-to-cell interfaces promote a variety of cellular responses such as repulsion, adhesion, attraction, and migration, and frequently occur during organ development, including vessel formation. Elaborate coordination of Eph- and ephrin-related signaling among different cell populations is required for proper formation of the embryonic vessel network. There is growing evidence supporting the idea that Eph and ephrin proteins also have postnatal interactions with a number of other membrane-associated signal transduction pathways, coordinating translation of environmental signals into cells. This article provides an overview of membrane-bound signaling mechanisms that define vascular identity in both the embryo and the adult, focusing on Eph- and ephrin-related signaling. We also discuss the role and clinical significance of this signaling system in normal organ development, neoplasms, and vascular pathologies. PMID- 26992087 TI - A dual system formed by the ARC and NR molybdoenzymes mediates nitrite-dependent NO production in Chlamydomonas. AB - Nitric oxide (NO) is a relevant signal molecule involved in many plant processes. However, the mechanisms and proteins responsible for its synthesis are scarcely known. In most photosynthetic organisms NO synthases have not been identified, and Nitrate Reductase (NR) has been proposed as the main enzymatic NO source, a process that in vitro is also catalysed by other molybdoenzymes. By studying transcriptional regulation, enzyme approaches, activity assays with in vitro purified proteins and in vivo and in vitro NO determinations, we have addressed the role of NR and Amidoxime Reducing Component (ARC) in the NO synthesis process. N?R and ARC were intimately related both at transcriptional and activity level. Thus, arc mutants showed high NIA1 (NR gene) expression and NR activity. Conversely, mutants without active NR displayed an increased ARC expression in nitrite medium. Our results with nia1 and arc mutants and with purified enzymes support that ARC catalyses the NO production from nitrite taking electrons from NR and not from Cytb5-1/Cytb5-Reductase, the component partners previously described for ARC (proposed as NOFNiR, Nitric Oxide-Forming Nitrite Reductase). This NR-ARC dual system would be able to produce NO in the presence of nitrate, condition under which NR is unable to do it. PMID- 26992088 TI - Pemetrexed-induced scleroderma-like conditions in the lower legs of a patient with non-small cell lung carcinoma. AB - Pemetrexed, which is used for the treatment of non-small cell lung carcinoma and malignant mesothelioma, induces cutaneous adverse reactions in approximately 20% of patients. There are also reports of the induction of fibrosing disorders. We describe a case of pemetrexed-induced scleroderma-like conditions in the lower legs of a patient whose pulmonary carcinoma has been relatively well controlled, with prolongation of the dose interval, in spite of the discomfort in both his legs. Skin biopsy revealed dermal fibrosis and dilated lymph vessels in the dermis, but lymphocytic infiltration around the lymph vessels, in contrast to the blood vessels, was minimal. Immunohistochemical staining revealed that the major subsets of T cells that had infiltrated around blood vessels were CD3 and CD45Ro, but no B cells were detected. High serum levels of interleukin (IL)-4 and IL-6 suggested that T cells, which secrete these cytokines, may be involved in the pathogenesis of this condition. Magnetic resonance imaging of the lower extremities revealed muscular and fascial involvement. Several chemotherapeutic agents, such as taxanes, gemcitabine and bleomycin, are known to induce scleroderma-like changes, and we should also keep the side-effects of pemetrexed in mind when we encounter patients with fibrosing conditions. PMID- 26992089 TI - Gleason and Fuhrman no longer make the grade. PMID- 26992090 TI - Identification of metformin poor responders, requiring supplemental insulin, during randomization of metformin versus insulin for the control of gestational diabetes mellitus. AB - AIM: To evaluate glycemic control among women with gestational diabetes mellitus (GDM) under insulin versus metformin (with or without insulin supplementation), and to identify metformin poor responders requiring supplemental insulin. METHODS: In Ain Shams University Hospital, mothers with 26-32-week GDM pregnancies, failing diet control, were randomized to receive metformin (n = 47) or insulin (n = 48). The primary outcome was glycemic control. Secondary outcomes included maternal weight, parameters predicting successful metformin monotherapy, neonatal hypoglycemia, and birthweight. RESULTS: Women using metformin (23.4% needing supplemental insulin) gained less weight (P < 0.001), and had lower fasting glucose during the first and last 2 weeks of treatment (P = 0.014 and 0.008, respectively) when compared with insulin monotherapy. Insulin supplementation in the metformin group was related to initial body mass index, HbA1c, oral glucose tolerance test (GTT), and first week mean glucose level. The 1-h glucose level during initial GTT (Hr1-GTT) and the mean fasting glucose level during the first week of therapy (Wk1-mFG) were the two independent parameters associated with requiring supplemental insulin. Women with Hr1-GTT >212 mg/dL and Wk1-mFG >95 mg/dL had a risk ratio of 58.6 (95%CI: 3.68-933.35, P = 0.004) and 11.5 (95%CI: 2.77-47.34,= 0.0008), respectively for needing supplemental insulin during the course of the study compared with women without. CONCLUSION: Metformin is an effective and safe alternative to insulin in GDM. Women using metformin (+/ supplemental insulin) had similar glycemic control, less weight gain, and similar rates of side-effects as those on insulin monotherapy. Insulin supplementation to metformin therapy was more likely with elevated Hr1-GTT and Wk1-mFG. PMID- 26992091 TI - Using Dynamic Risk to Enhance Conditional Release Decisions in Prisoners to Improve Their Outcomes. AB - Advances in criminal risk assessment have increased sufficiently that inclusion of valid risk measures to anchor assessments is considered a best practice in release decision-making and community supervision by many paroling authorities and probation agencies. This article highlights how decision accuracy at several key stages of the offender's release and supervision process could be further enhanced by the inclusion of dynamic factors. In cases where the timing of release is discretionary and not legislated, the utilization of a validated decision framework can improve transparency and potentially reduce decision errors. In cases where release is by statute, there is still merit in using dynamic risk assessment and case analysis to inform the assignment of release conditions, thereby attending to re-entry and public safety considerations. Finally, preliminary results from a recent study are presented to highlight the fact that community supervision outcomes may be improved by incorporating changes in dynamic risk into case planning and risk management, although this work requires replication with larger populations reflecting diverse groups of offenders. Nonetheless, these decision strategies have implications for both resource allocation and client outcomes, as outlined here. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26992092 TI - Diagnostic performance of 1,3-beta-D-glucan serum screening in patients receiving hematopoietic stem cell transplantation. AB - BACKGROUND: The polysaccharide cell wall component, 1,3-beta-D-glucan (BDG), is used as a serum biomarker for invasive fungal infection (IFI). Patients receiving hematopoietic stem cell transplantation (HSCT) are considered a highly vulnerable group for IFI development. We evaluated the diagnostic performance of serum BDG screening in HSCT recipients. METHODS: HSCT recipients were prospectively enrolled in this study between September 2014 and August 2015. Routine serum BDG screening was performed 2-3 times weekly by using the Fungitell((r)) assay. All samples were classified according to the 2008 EORTC/MSG criteria, with serum BDG results not being considered for classification. The diagnostic performance of BDG testing for IFI was calculated. BDG values >=80 pg/mL were considered positive. RESULTS: A total of 308 serum samples were collected in 45 patients. The majority of 172 samples (55.8%) were obtained at the early phase (within 30 days) after allogeneic HSCT. BDG levels were significantly higher in 16 possible/probable IFI samples when compared to no evidence for IFI samples (median 170 pg/mL, interquartile range [IQR] 100-274 pg/mL vs. median 15 pg/mL, IQR 15-15 pg/mL; P < 0.001, Mann-Whitney U-test). Diagnostic performance of serum BDG screening for possible IFI/probable invasive pulmonary aspergillosis vs. no evidence for IFI was as follows: sensitivity 81%, specificity 98%, positive predictive value 65%, negative predictive value (NPV) 99%, and diagnostic odds ratio 176 (95% confidence interval 41-761). CONCLUSIONS: Our data suggest that serum BDG testing in HSCT patients may be highly specific and associated with a very high NPV of >99%. Therefore, serum BDG may be a helpful tool to rule out IFI in HSCT patients. PMID- 26992093 TI - Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome. AB - The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle. PMID- 26992096 TI - Twenty-Four-Hour Urine alpha1 -Microglobulin as a Marker of Hypertension-Induced Renal Impairment and Its Response on Different Blood Pressure-Lowering Drugs. AB - The purpose of this study was to assess the role of urine alpha1 -microglobulin as a marker of hypertension-induced renal damage compared with estimated glomerular filtration rate, (eGFR), urine albumin, and urine albumin-to creatinine ratio (ACR). Its response on different blood pressure (BP)-lowering drugs was also studied. Sixty never-treated hypertensive patients (65.0% men, 46.9 years, BP 141.4/94.0 mm Hg) were randomized to an irbesartan (an angiotensin receptor blocker [ARB]) or a diltiazem (a nondihydropyridine calcium channel blocker [CCB])-based regimen. Patients with diabetes or established cardiovascular, renal, or liver disease were excluded. Blood samples and 24-hour urine were analyzed at baseline and 6 months after pharmaceutical BP normalization. Serum creatinine was measured and eGFR was calculated. Urine albumin, creatinine, and alpha1 -microglobulin were measured and ACR was calculated. Minor changes (P=not significant [NS]) in eGFR were noted during follow-up in both groups (from 111.0 mL/min/1.73 m2 to 108.4 mL/min/1.73 m2 in the ARB group and from 111.3 mL/min/1.73 m2 to 114.0 mL/min/1.73 m2 in the CCB group). Twenty-four-hour urine indices were all significantly improved (P<.01) in the ARB group (albumin from 19.4 mg/L to 8.2 mg/L, ACR from 21.5 mg/g to 10.0 mg/g, alpha1 -microglobulin from 5.06 mg/L to 3.64 mg/L) but not (P=NS) in the CCB group (albumin from 15.6 mg/L to 13.9 mg/L, ACR from 17.6 mg/g to 17.1 mg/g, alpha1 -microglobulin from 4.94 mg/L to 4.79 mg/L). These differences between groups remained significant (P<.05) after adjusting for office heart rate and BP. alpha1 -Microglobulin was significantly correlated (P<.05) with albumin and ACR both at baseline (r=0.283 and 0.299, respectively) and at the end of follow-up (r=0.432 and 0.465, respectively) but not (P=NS) with eGFR. It was also significantly related (P<.05) to cardiovascular risk scores (Framingham and HeartScore) both at baseline (r=0.264 and 0.436, respectively) and at the end of follow-up (r=0.308 and 0.472, respectively). Urine alpha1 -microglobulin emerges as a potentially usable marker of hypertension-induced renal impairment. Its excretion rate and its response to treatment appears similar to that of albumin. Irbesartan but not diltiazem seems to be associated with reduced excretion of alpha1 -microglobulin in urine. PMID- 26992095 TI - Augmented Pain Processing in Primary and Secondary Somatosensory Cortex in Fibromyalgia: A Magnetoencephalography Study Using Intra-Epidermal Electrical Stimulation. AB - The aim of this study was to investigate augmented pain processing in the cortical somatosensory system in patients with fibromyalgia (FM). Cortical evoked responses were recorded in FM (n = 19) and healthy subjects (n = 21) using magnetoencephalography after noxious intra-epidermal electrical stimulation (IES) of the hand dorsum (pain rating 6 on a numeric rating scale, perceptually equivalent). In addition, healthy subjects were stimulated using the amplitude corresponding to the average stimulus intensity rated 6 in patients with FM (intensity-equivalent). Quantitative sensory testing was performed on the hand dorsum or thenar muscle (neutral site) and over the trapezius muscle (tender point), using IES (thresholds, ratings, temporal summation of pain, stimulus response curve) and mechanical stimuli (threshold, ratings). Increased amplitude of cortical responses was found in patients with FM as compared to healthy subjects. These included the contralateral primary (S1) and bilateral secondary somatosensory cortices (S2) in response to intensity-equivalent stimuli and the contralateral S1 and S2 in response to perceptually-equivalent stimuli. The amplitude of the contralateral S2 response in patients with FM was positively correlated with average pain intensity over the last week. Quantitative sensory testing results showed that patients with FM were more sensitive to painful IES as well as to mechanical stimulation, regardless of whether the stimulation site was the hand or the trapezius muscle. Interestingly, the slope of the stimulus response relationship as well as temporal summation of pain in response to IES was not different between groups. Together, these results suggest that the observed pain augmentation in response to IES in patients with FM could be due to sensitization or disinhibition of the cortical somatosensory system. Since the S2 has been shown to play a role in higher-order functions, further studies are needed to clarify the role of augmented S2 response in clinical characteristics of FM. PMID- 26992097 TI - Decreasing Nitrogen Fertilizer Input Had Little Effect on Microbial Communities in Three Types of Soils. AB - In this study, we examined the influence of different nitrogen (N) application rates (0, 168, 240, 270 and 312 kg N ha(-1)) on soil properties, maize (Zea mays L.) yields and microbial communities of three types of soils (clay, alluvial and sandy soils). Phospholipid fatty acid analysis was used to characterize soil microbial communities. Results indicated that N fertilization significantly decreased microbial biomass in both clay and sandy soils regardless of application rate. These decreases were more likely a result of soil pH decreases induced by N fertilization, especially in the sandy soils. This is supported by structural equation modeling and redundancy analysis results. Nitrogen fertilization also led to significant changes in soil microbial community composition. However, the change differences were gradually dismissed with increase in N application rate. We also observed that N fertilization increased maize yields to the same level regardless of application rate. This suggests that farmers could apply N fertilizers at a lower rate (i.e. 168 kg N ha(-1)), which could achieve high maize yield on one hand while maintain soil microbial functions on the other hand. PMID- 26992098 TI - Determinants of biofilm formation and cleanability of titanium surfaces. AB - OBJECTIVE: The aim of the present study was to analyze biofilm formation on four different titanium-based surfaces (machined titanium zirconium (TiZr) alloy, M; machined, acid-etched TiZr alloy, modMA; machined, sandblasted, acid-etched TiZr alloy, modSLA; and micro-grooved titanium aluminum vanadium alloy, TAV MG) in an experimental human model. MATERIAL AND METHODS: Custom-made discs were mounted in individual intraoral splint housings and worn by 16 volunteers for 24 h. The safranin staining assay, isothermal microcalorimetry (IMC), and SEM were applied before and after surface cleaning. RESULTS: The hydrophilic surfaces modMA and modSLA with greater surface micro-roughness exhibited significantly more biofilm than the hydrophobic surfaces TAV MG and M. The standardized cleaning procedure substantially reduced the biofilm mass on all surfaces. After cleaning, the IMC analyses demonstrated a longer lag time of the growth curve on TAV MG compared to modSLA. Inter- and intraindividual variations in biofilm formation on the titanium discs were evident throughout the study. CONCLUSIONS: Surface hydrophilicity and roughness enhanced biofilm formation in vivo, whereas surface topography was the most influential factor that determined surface cleanability. While the grooved surface retained larger amounts of initial biofilm, the machined surface was easier to clean, but proliferation indicated by increased metabolic activity (growth rate) in IMC occurred despite mechanical biofilm removal. PMID- 26992099 TI - Test-retest Reliability in Reporting the Pain Induced by a Pain Provocation Test: Further Validation of a Novel Approach for Pain Drawing Acquisition and Analysis. AB - BACKGROUND: Pain drawings (PD) are frequently used in research to illustrate the pain response to pain provocation tests. However, there is a lack of data on the reliability in defining the extent and location of pain. We investigated the test retest reliability in reporting an acute painful sensation induced by a pain provocation test using a novel approach for PD acquisition and analysis in healthy volunteers. METHODS: Forty healthy volunteers participated. Each participant underwent 2 upper limb neurodynamic tests 1 (ULNT1), once to the point of pain onset (PO) and once until the point of submaximal pain (SP). After each ULNT1, participants completed 2 consecutive PD with an interval of 1 minute. Custom software was used to quantify the pain extent and analyze the pain overlap. The test-retest reliability of pain extent was examined using Intraclass Correlation Coefficient (ICC 2,1 ) and Bland-Altman plots. Pain location reliability was examined using the Jaccard similarity coefficient (JSC). RESULTS: The ICC values for PO and SP were 0.98 (95% CI: 0.96-0.99) and 0.97 (95% CI: 0.95 0.98), respectively. The mean difference and 95% limits of agreement (+/- 1.96 SD) in the Bland-Altman plots were 14 pixels (-1080;1110) for PO, and 145 ( 1610;1900) for SP. The median JSCs (Q1;Q3) were 0.73 (0.64;0.80) for PO and 0.76 (0.65;0.79) for SP. CONCLUSIONS: Pain drawings is a reliable instrument to investigate pain extent and pain location in healthy individuals experiencing an acute painful sensation induced by a pain provocation test. PMID- 26992101 TI - Multi-Character Physical and Behavioral Interactions Controller. AB - We extend the quadratic program (QP)-based task-space character control approach initially intended for individual character animation-to multiple characters interacting among each other or with mobile/articulated elements of the environment. The interactions between the characters can be either physical interactions, such as contacts that can be established or broken at will between them and for which the forces are subjected to Newton's third law, or behavioral interactions, such as collision avoidance and cooperation that naturally emerge to achieve collaborative tasks from high-level specifications. We take a systematic approach integrating all the equations of motions of the characters, objects, and articulated environment parts in a single QP formulation in order to embrace and solve the most general instance of the problem, where independent individual character controllers would fail to account for the inherent coupling of their respective motions through those physical and behavioral interactions. Various types of motions/behaviors are controlled with only the one single formulation that we propose, and some examples of the original motions the framework allows are presented in the accompanying video. PMID- 26992102 TI - TOD-Tree: Task-Overlapped Direct Send Tree Image Compositing for Hybrid MPI Parallelism and GPUs. AB - Modern supercomputers have thousands of nodes, each with CPUs and/or GPUs capable of several teraflops. However, the network connecting these nodes is relatively slow, on the order of gigabits per second. For time-critical workloads such as interactive visualization, the bottleneck is no longer computation but communication. In this paper, we present an image compositing algorithm that works on both CPU-only and GPU-accelerated supercomputers and focuses on communication avoidance and overlapping communication with computation at the expense of evenly balancing the workload. The algorithm has three stages: a parallel direct send stage, followed by a tree compositing stage and a gather stage. We compare our algorithm with radix-k and binary-swap from the IceT library in a hybrid OpenMP/MPI setting on the Stampede and Edison supercomputers, show strong scaling results and explain how we generally achieve better performance than these two algorithms. We developed a GPU-based image compositing algorithm where we use CUDA kernels for computation and GPU Direct RDMA for inter node GPU communication. We tested the algorithm on the Piz Daint GPU-accelerated supercomputer and show that we achieve performance on par with CPUs. Last, we introduce a workflow in which both rendering and compositing are done on the GPU. PMID- 26992100 TI - The bacterial community of entomophilic nematodes and host beetles. AB - Insects form the most species-rich lineage of Eukaryotes and each is a potential host for organisms from multiple phyla, including fungi, protozoa, mites, bacteria and nematodes. In particular, beetles are known to be associated with distinct bacterial communities and entomophilic nematodes. While entomopathogenic nematodes require symbiotic bacteria to kill and reproduce inside their insect hosts, the microbial ecology that facilitates other types of nematode-insect associations is largely unknown. To illuminate detailed patterns of the tritrophic beetle-nematode-bacteria relationship, we surveyed the nematode infestation profiles of scarab beetles in the greater Los Angeles area over a five-year period and found distinct nematode infestation patterns for certain beetle hosts. Over a single season, we characterized the bacterial communities of beetles and their associated nematodes using high-throughput sequencing of the 16S rRNA gene. We found significant differences in bacterial community composition among the five prevalent beetle host species, independent of geographical origin. Anaerobes Synergistaceae and sulphate-reducing Desulfovibrionaceae were most abundant in Amblonoxia beetles, while Enterobacteriaceae and Lachnospiraceae were common in Cyclocephala beetles. Unlike entomopathogenic nematodes that carry bacterial symbionts, insect associated nematodes do not alter the beetles' native bacterial communities, nor do their microbiomes differ according to nematode or beetle host species. The conservation of Diplogastrid nematodes associations with Melolonthinae beetles and sulphate-reducing bacteria suggests a possible link between beetle-bacterial communities and their associated nematodes. Our results establish a starting point towards understanding the dynamic interactions between soil macroinvertebrates and their microbiota in a highly accessible urban environment. PMID- 26992103 TI - Spherical Parameterization Balancing Angle and Area Distortions. AB - This work presents a novel framework for spherical mesh parameterization. An efficient angle-preserving spherical parameterization algorithm is introduced, which is based on dynamic Yamabe flow and the conformal welding method with solid theoretic foundation. An area-preserving spherical parameterization is also discussed, which is based on discrete optimal mass transport theory. Furthermore, a spherical parameterization algorithm, which is based on the polar decomposition method, balancing angle distortion and area distortion is presented. The algorithms are tested on 3D geometric data and the experiments demonstrate the efficiency and efficacy of the proposed methods. PMID- 26992104 TI - Microbial Populations in Naked Neck Chicken Ceca Raised on Pasture Flock Fed with Commercial Yeast Cell Wall Prebiotics via an Illumina MiSeq Platform. AB - Prebiotics are non-digestible carbohydrate dietary supplements that selectively stimulate the growth of one or more beneficial bacteria in the gastrointestinal tract of the host. These bacteria can inhibit colonization of pathogenic bacteria by producing antimicrobial substances such as short chain fatty acids (SCFAs) and competing for niches with pathogens within the gut. Pasture flock chickens are generally raised outdoors with fresh grass, sunlight and air, which represents different environmental growth conditions compared to conventionally raised chickens. The purpose of this study was to evaluate the difference in microbial populations from naked neck chicken ceca fed with commercial prebiotics derived from brewer's yeast cell wall via an Illumina MiSeq platform. A total of 147 day of-hatch naked neck chickens were distributed into 3 groups consisted of 1) C: control (no prebiotic), 2) T1: Biolex(r) MB40 with 0.2%, and 3) T2: Leiber(r) ExCel with 0.2%, consistently supplemented prebiotics during the experimental period. At 8 weeks, a total of 15 birds from each group were randomly selected and ceca removed for DNA extraction. The Illumina Miseq platform based on V4 region of 16S rRNA gene was applied for microbiome analysis. Both treatments exhibited limited impact on the microbial populations at the phylum level, with no significant differences in the OTU number of Bacteroidetes among groups and an increase of Proteobacteria OTUs for the T1 (Biolex(r) MB40) group. In addition there was a significant increase of genus Faecalibacterium OTU, phylum Firmicutes. According to the development of next generation sequencing (NGS), microbiome analysis based on 16S rRNA gene proved to be informative on the prebiotic impact on poultry gut microbiota in pasture-raised naked neck birds. PMID- 26992105 TI - Intermittent Malfunction of a Prosthetic Valve-A Diagnostic Challenge. AB - Intermittent malfunction of a mechanical valve prosthesis is a rare condition that carries serious clinical implications. It results from the periodic entrapment of a prosthetic disk in either an open or closed position leading to transient intravalvular regurgitation or obstruction to flow. The intermittent nature of the malfunction poses a diagnostic challenge, particularly in the era of digital echocardiography. In this manuscript, we describe the Doppler and two dimensional echocardiographic findings in a patient with intermittent prosthetic mitral valve malfunction. PMID- 26992106 TI - Cumulative Corticosteroid Dose Over Fifty-Two Weeks in Patients With Systemic Lupus Erythematosus: Pooled Analyses From the Phase III Belimumab Trials. AB - OBJECTIVE: To examine the effects of treatment with belimumab on corticosteroid dose in patients with systemic lupus erythematosus (SLE) over 52 weeks in 2 randomized, controlled trials. METHODS: Data on patients who were taking corticosteroids at baseline in the Study of Belimumab in Subjects with SLE trials were pooled post hoc to compare patients who received belimumab 10 mg/kg plus standard therapy with those who received placebo plus standard therapy. The primary end point was cumulative change from baseline in corticosteroid dose (prednisone equivalent) through week 52. Further analyses specifically examined oral corticosteroid dose. RESULTS: At baseline, 966 of 1,125 patients (86%) were receiving corticosteroids (478 belimumab 10 mg/kg and 488 placebo). Most were women (94%), their mean age was 37.1 years, mean Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index score was 9.8, and mean corticosteroid dosage was 12.5 mg/day. Over 52 weeks, there was a smaller increase in mean cumulative corticosteroid dose for the belimumab group than for the placebo group (531.2 mg versus 916.3 mg; P < 0.0001). Compared with placebo, the mean of all decreases in cumulative corticosteroid dose was higher with belimumab (P = 0.0165), and the mean of all increases was lower (P = 0.0005). More patients in the belimumab group had decreases in oral corticosteroid dose (38.5% versus 30.9%), and fewer had increases in dose (18.4% versus 30.7%), compared with placebo. Adverse events were comparable across groups. CONCLUSION: Our findings show a significantly smaller increase in cumulative corticosteroid dose over 1 year, more patients with decreases in oral corticosteroid dose, and fewer patients with increases in oral corticosteroid dose in the belimumab group compared with the placebo group. These data suggest that belimumab may be steroid sparing. PMID- 26992107 TI - Achieving and maintaining quality of care in inflammatory bowel disease: The Crohn's and Colitis Australia audit. PMID- 26992108 TI - Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort. AB - OBJECTIVE: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. METHODS: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. RESULTS: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. CONCLUSION: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase. PMID- 26992110 TI - Is the prevalence of colonic neuroendocrine tumors increased in patients with inflammatory bowel disease? AB - Inflammatory bowel disease (IBD) patients may bear an increased neuroendocrine tumor (NET) risk. These tumors are mostly reported as coincidental findings during surgery. We aimed to determine the prevalence of colonic NET in a Dutch nationwide IBD cohort and calculate the prevalence rate ratios (PRR) compared with the general Dutch population. Our second aim was to investigate whether a high bowel surgery rate in IBD could result in a high PRR for NET. The Dutch Pathology Registry (PALGA) was searched to identify all IBD patients with colonic NET in The Netherlands between 1991 and 2011. We determined the prevalence and PRR of colonic NET in a 20-year period. For our second aim, we compared NET prevalence in colonic resection specimens between IBD cases and non-IBD controls (diverticulitis and ischemia). We identified 51 IBD patients who developed colonic NET resulting in a prevalence of 60.4-89.3 per 100,000 patients in a 20 year period with a PRR of 2.8-4.1. However, adjusted for resection type, sex and age, a higher NET prevalence was shown in diverticulitis (OR 5.52, 95% CI 3.47 8.78) and ischemia (OR 1.97, 95% CI 1.09-3.58) compared with IBD. Our key finding is that NET are more prevalent in IBD patients compared with the general population (PRR 2.8-4.1). This might be attributed to a high rate of incidental NET as IBD patients frequently undergo intestinal surgery. A lower adjusted NET prevalence in colonic resection specimens for IBD compared to ischemia and diverticulitis supports this hypothesis. PMID- 26992109 TI - Impact of end-of-life discussions on the reduction of Latino/non-Latino disparities in do-not-resuscitate order completion. AB - BACKGROUND: Compared with non-Latino, white patients with advanced cancer, Latino patients with advanced cancer are less likely to sign do-not-resuscitate (DNR) orders, which is a form of advance care planning associated with better quality of life at the end of life (EOL). Latinos' completion of DNR orders may be more sensitive to clinical discussions regarding EOL care. The current study examined differences between Latino and white terminally ill patients with cancer with regard to the association between EOL discussions and DNR order completion. METHODS: A total of 117 participants with advanced cancer (61 of whom were Latino and 56 of whom were non-Latino white individuals) were recruited between 2002 and 2008 from Parkland Hospital (a public hospital in Dallas, Texas) as part of the Coping with Cancer study, which is a large, multiinstitutional, prospective cohort study of patients with advanced cancer that is designed to examine social and psychological influences on EOL care. In structured interviews, patients reported if they had EOL discussions with their physicians, and if they completed DNR orders. RESULTS: The association between EOL discussions and DNR order completion was significantly greater in Latino compared with white patients, adjusting for potential confounds (interaction adjusted odds ratio, 6.64; P = .041). Latino patients who had an EOL discussion were >10 times more likely (adjusted odds ratio, 10.91; P = .001) to complete a DNR order than those who had not, and were found to be equally as likely to complete a DNR order as white patients. CONCLUSIONS: Differences in the impact of EOL discussions on DNR order completion may explain Latino/non-Latino ethnic disparities in DNR order completion in EOL care, and point to a means to eliminate those disparities. Cancer 2016;122:1749-56. (c) 2016 American Cancer Society. PMID- 26992111 TI - Back to the future: function-first metagenomics returns to the fore. PMID- 26992112 TI - Bioassay-Guided Isolation and Structural Modification of the Anti-TB Resorcinols from Ardisia gigantifolia. AB - Tuberculosis (TB) is a highly contagious disease mainly caused by Mycobacterium tuberculosis H37 RV . Antitubercular (anti-TB) bioassay-guided isolation of the CHCl3 extract of the leaves and stems of the medicinal plant Ardisia gigantifolia led to the isolation of two anti-TB 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2). We further synthesized 15 derivatives based on these two natural products. These compounds (natural and synthetic) were evaluated for their anti-TB activity against Mycobacterium tuberculosis H37 RV . Resorcinols 1 and 2 exhibited anti-TB activity with MIC values at 34.4 and 79.2 MUm in MABA assay, respectively, and 91.7 and 168.3 MUm in LORA assay, respectively. Among these derivatives, compound 8 was found to show improved anti-TB activity than its synthetic precursor (2) with MIC values at 42.0 MUm in MABA assay and 100.2 MUm in LORA assay. The active compounds should be regarded as new hits for further study as a novel class of anti-TB agents. The distinct structure-activity correlations of the parent compound were elucidated based on these derivatives. PMID- 26992113 TI - Costs of Health Damage from Atmospheric Emissions of Toxic Metals: Part 2 Analysis for Mercury and Lead. AB - In this part of the series we explain the detailed literature review and the calculations of impacts and damage costs of mercury and lead. Methodology and general assumptions are explained in the companion article, Part 1 of this series, and the spreadsheet with the calculations is available as a supplementary file of Part 1.3 For mercury, the damage cost is 22,937 ?2013 /kg if there is a no-effect threshold, 52,129 ?2013 /kg if there is none; 91% is due to mortality from heart disease, the rest from loss of IQ points. For lead, the damage cost is 29,343 ?2013 /kg, about 80% due to mortality and 20% due to IQ loss; there does not seem to be a no-effect threshold. These costs are per kg of emitted pollutant. PMID- 26992114 TI - Small Molecules for Active Targeting in Cancer. AB - For the purpose of this review, active targeting in cancer research encompasses strategies wherein a ligand for a cell surface receptor expressed on tumor cells is used to deliver a cytotoxic or imaging cargo. This area of research is more than two decades old, but in those 20 and more years, how many receptors have been studied extensively? What kinds of the ligands are used for active targeting? Are they mostly naturally occurring molecules such as folic acid, or synthetic substances developed in campaigns for medicinal chemistry efforts? This review outlines the most important receptor or ligand combinations that have been used in active targeting to answer these questions, and therefore to address the most important one of all: is research in active targeting affording diminishing returns, or is this an area for which the potential far exceeds progress made so far? PMID- 26992115 TI - RESOLVE: bioabsorbable steroid-eluting sinus implants for in-office treatment of recurrent sinonasal polyposis after sinus surgery: 6-month outcomes from a randomized, controlled, blinded study. AB - BACKGROUND: Patients with recurrent sinonasal polyposis after endoscopic sinus surgery (ESS) have limited treatment options. Safety and efficacy were previously reported for a bioabsorbable sinus implant that elutes mometasone furoate for 3 months. Here we summarize longer-term outcomes. METHODS: A randomized, controlled, blinded study with 100 chronic rhinosinusitis with nasal polyps (CRSwNP) patients who failed medical treatment and were considered candidates for revision ESS. Treated patients (n = 57) underwent in-office implant placement. Control patients (n = 43) underwent a sham procedure. Endoscopic grading at 3 months by clinicians was corroborated by an independent review of randomized videoendoscopies by a panel of 3 sinus surgeons. Six-month follow-up included endoscopic grading and patient-reported outcomes. RESULTS: At 6 months, treated patients experienced significant improvement in Nasal Obstruction Symptom Evaluation (NOSE) score (p = 0.021) and >2-fold improvement in mean nasal obstruction/congestion score (-1.06 +/- 1.4 vs -0.44 +/- 1.4; p = 0.124). Endoscopically, treated patients experienced significant reduction in ethmoid sinus obstruction (p < 0.001) and bilateral polyp grade (p = 0.018) compared to controls. Panel review confirmed a significant reduction in ethmoid sinus obstruction (p = 0.010) and 2-fold improvement in bilateral polyp grade (p = 0.099), which reached statistical significance (p = 0.049) in a subset of 67 patients with baseline polyp burden >=2 bilaterally. At 6 months, control patients were at 3.6 times higher risk of remaining indicated for ESS than treated patients. CONCLUSION: The symptomatic and endoscopic improvements observed confirm the efficacy of the steroid-eluting implant for in-office treatment of CRSwNP after ESS. These longer-term 6-month study results demonstrate that the steroid-eluting implant represents a durable, safe, and effective treatment strategy for this patient population. PMID- 26992116 TI - Role of Epstein-Barr virus status and immunophenotypic studies in the evaluation of exfoliative cytology specimens from patients with post-transplant lymphoproliferative disorders. AB - BACKGROUND: Post-transplant lymphoproliferative disorders (PTLDs) are well characterized in tissue sections, but their evaluation in exfoliative cytology specimens is limited. This study reports a 25-year experience with PTLDs in exfoliative cytology specimens. METHODS: All solid organ or allogeneic stem cell transplant recipients with PTLDs and exfoliative cytology specimens from 1987 to 2011 were identified. The cytomorphology, Epstein-Barr virus (EBV) status, flow cytometry, immunohistochemistry, and molecular studies were reviewed from all exfoliative cytology specimens previously diagnosed as atypical lymphoid proliferations or PTLDs. RESULTS: A total of 55 patients (age range, 1-72 years) with PTLDs had 434 exfoliative cytology specimens. Thirty-six of the 55 patients (65%) had 54 specimens with abnormal lymphoid proliferations (12% of the specimens), and 26 of these patients had 37 specimens available for review (15 cerebrospinal fluid specimens, 12 peritoneal fluid specimens, 9 pleural fluid specimens, and 1 bronchoalveolar lavage fluid specimen). Thirty percent of the reviewed cytology specimens were diagnostic of PTLDs, including 8 cases of monomorphic post-transplant lymphoproliferative disorder (M-PTLD) with abnormal B/T-cell populations identified with flow cytometry/immunohistochemistry and 3 EBV-positive specimens with a differential diagnosis of polymorphic PTLD versus M PTLD. All cases diagnostic of a PTLD had 1 to 3 ancillary studies performed. Forty percent of the cytology specimens (15 of 37) were suspicious for a PTLD, but ancillary studies were performed for only a third of them, and they did not support a definitive diagnosis of a PTLD. Thirty percent of the cytology specimens (11 of 37) appeared reactive, but they lacked sufficient ancillary studies to exclude a PTLD. CONCLUSIONS: Atypical lymphoid proliferations are common in exfoliative cytology specimens from patients with PTLDs, and they require ancillary studies at least including immunophenotyping and EBV evaluations for a definitive diagnosis. Cancer Cytopathol 2016;124:425-35. (c) 2016 American Cancer Society. PMID- 26992118 TI - Flavonoids intake and risk of prostate cancer: a meta-analysis of observational studies. AB - The aim of the study was to assess the association between total flavonoids/flavonoid subclasses intake and prostate cancer risk. Several databases were searched to select eligible studies with predefined criteria. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the effect size. Publication bias and sensitivity analysis were performed. A total of five studies including four prospective cohort studies and one case-control study were included in the meta-analysis. The pooled result demonstrated a significantly increased risk of prostate cancer with higher intake of total flavonoids (RR = 1.12, 95% CI: 1.02-1.23, P = 0.013). However, sensitivity analysis indicated that there lacked a significant association after removing the study of Wang et al. (RR = 1.17, 95% CI: 0.94-1.46). Subgroup analysis stratified by flavonoids subclasses found that higher intake of anthocyanidins and flavan-3-ols were significantly associated with increased prostate cancer risk (RR = 1.12, 95% CI: 1.03-1.21, P = 0.011; RR = 1.21, 95% CI: 1.10-1.32, P < 0.001). Sensitivity analysis also indicated that after removing Wang's study, no significant association between anthocyanidins intake and prostate cancer risk was detected (RR = 1.22, 95% CI: 0.97-1.54). In conclusion, higher intake of flavonoids may not be associated with prostate cancer risk. PMID- 26992117 TI - Hydrophobicity of Antifungal beta-Peptides Is Associated with Their Cytotoxic Effect on In Vitro Human Colon Caco-2 and Liver HepG2 Cells. AB - The widespread distribution of fungal infections, with their high morbidity and mortality rate, is a global public health problem. The increase in the population of immunocompromised patients combined with the selectivity of currents treatments and the emergence of drug-resistant fungal strains are among the most imperative reasons to develop novel antifungal formulations. Antimicrobial beta peptides are peptidomimetics of natural antimicrobial peptides (AMPs), which have been proposed as developmental platforms to enhance the AMPs selectivity and biostability. Their tunability allows the design of sequences with remarkable activity against a wide spectrum of microorganisms such as the human pathogenic Candida spp., both in planktonic and biofilm morphology. However, the beta peptide's effect on surrounding host cells remains greatly understudied. Assessments have mainly relied on the extent of hemolysis that a candidate peptide is able to cause. This work investigated the in vitro cytotoxicity of various beta-peptides in the Caco-2 and HepG2 mammalian cell lines. Results indicated that the cytotoxic effect of the beta-peptides was influenced by cell type and was also correlated to structural features of the peptide such as hydrophobicity. We found that the selectivity of the most hydrophobic beta peptide was 2-3 times higher than that of the least hydrophobic one, for both cell types according to the selectivity index parameter (IC50/MIC). The IC50 of Caco-2 and HepG2 increased with hydrophobicity, which indicates the importance of testing putative therapeutics on different cell types. We report evidence of peptide-cell membrane interactions in Caco-2 and HepG2 using a widely studied beta-peptide against C. albicans. PMID- 26992119 TI - Electrophysiological indices of brain activity to content and function words in discourse. AB - BACKGROUND: An increase in positivity of event-related potentials (ERPs) at the lateral anterior sites has been hypothesized to be an index of semantic and discourse processing, with the right lateral anterior positivity (LAP) showing particular sensitivity to discourse factors. However, the research investigating the LAP is limited; it is unclear whether the effect is driven by word class (function word versus content word) or by a more general process of structure building triggered by elements of a determiner phrase (DP). AIMS: To examine the neurophysiological indices of semantic/discourse integration using two different word categories (function versus content word) in the discourse contexts and to contrast processing of these word categories in meaningful versus nonsense contexts. METHODS & PROCEDURES: Planned comparisons of ERPs time locked to a function word stimulus 'the' and a content word stimulus 'cats' in sentence initial position were conducted in both discourse and nonsense contexts to examine the time course of processing following these word forms. OUTCOMES & RESULTS: A repeated-measures analysis of variance (ANOVA) for the Discourse context revealed a significant interaction of condition and site due to greater positivity for 'the' relative to 'cats' at anterior and superior sites. In the Nonsense context, there was a significant interaction of condition, time and site due to greater positivity for 'the' relative to 'cats' at anterior sites from 150 to 350 ms post-stimulus offset and at superior sites from 150 to 200 ms post stimulus offset. Overall, greater positivity for both 'the' and 'cats' was observed in the discourse relative to the nonsense context beginning approximately 150 ms post-stimulus offset. Additionally, topographical analyses were highly correlated for the two word categories when processing meaningful discourse. This topographical pattern could be characterized as a prominent right LAP. The LAP was attenuated when the target stimulus word initiated a nonsense context. CONCLUSIONS & IMPLICATIONS: The results of this study support the view that the right LAP is an index of general discourse processing rather than an index of word class. These findings demonstrate that the LAP can be used to study discourse processing in populations with compromised metalinguistic skills, such as adults with aphasia or traumatic brain injury. PMID- 26992121 TI - A Systematic Review on the Health Effects of Plums (Prunus domestica and Prunus salicina). AB - In recent times, plums have been described as foods with health-promoting properties. Research on the health effects of plum continue to show promising results on its antiinflammatory, antioxidant and memory-improving characteristics. The increased interest in plum research has been attributed to its high phenolic content, mostly the anthocyanins, which are known to be natural antioxidants. A systematic review of literature was carried out to summarize the available evidence on the impact of plums (Prunus species; domestica and salicina) on disease risk factors and health outcomes. A number of databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for relevant studies on plum health effects in vitro, animal studies and clinical trials. A total of 73 relevant peer-reviewed journal articles were included in this review. The level of evidence remains low. Of the 25 human studies, 6 were confirmatory studies of moderate quality, while 19 were exploratory. Plums have been shown to possess antioxidant and antiallergic properties, and consumption is associated with improved cognitive function, bone health parameters and cardiovascular risk factors. Most of the human trials used the dried version of plums rather than fresh fruit, thus limiting translation to dietary messages of the positioning of plums in a healthy diet. Evidence on the health effect of plums has not been extensively studied, and the available evidence needs further confirmation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26992120 TI - Subthreshold nitric oxide synthase inhibition improves synergistic effects of subthreshold MMP-2/MLCK-mediated cardiomyocyte protection from hypoxic injury. AB - Injury of myocardium during ischaemia/reperfusion (I/R) is a complex and multifactorial process involving uncontrolled protein phosphorylation, nitration/nitrosylation by increased production of nitric oxide and accelerated contractile protein degradation by matrix metalloproteinase-2 (MMP-2). It has been shown that simultaneous inhibition of MMP-2 with doxycycline (Doxy) and myosin light chain kinase (MLCK) with ML-7 at subthreshold concentrations protects the heart from contractile dysfunction triggered by I/R in a synergistic manner. In this study, we showed that additional co-administration of nitric oxide synthase (NOS) inhibitor (1400W or L-NAME) in subthreshold concentrations improves this synergistic protection in the model of hypoxia-reoxygenation (H-R) induced contractile dysfunction of cardiomyocytes. Isolated cardiomyocytes were subjected to 3 min. of hypoxia and 20 min. of reoxygenation in the presence or absence of the inhibitor cocktails. Contractility of cardiomyocytes was expressed as myocyte peak shortening. Inhibition of MMP-2 by Doxy (25-100 MUM), MLCK by ML 7 (0.5-5 MUM) and NOS by L-NAME (25-100 MUM) or 1400W (25-100 MUM) protected myocyte contractility after H-R in a concentration-dependent manner. Inhibition of these activities resulted in full recovery of cardiomyocyte contractility after H-R at the level of highest single-drug concentration. The combination of subthreshold concentrations of NOS, MMP-2 and MLCK inhibitors fully protected cardiomyocyte contractility and MLC1 from degradation by MMP-2. The observed protection with addition of L-NAME or 1400W was better than previously reported combination of ML-7 and Doxy. The results of this study suggest that addition of NOS inhibitor to the mixture of inhibitors is better strategy for protecting cardiomyocyte contractility. PMID- 26992122 TI - The Quality Changes of Postharvest Mulberry Fruit Treated by Chitosan-g-Caffeic Acid During Cold Storage. AB - This study aimed to characterize the effects of chitosan-g-caffeic acid (CTS-g CA) on improving the quality and extending the shelf life of postharvest mulberry fruit during storage at 4 degrees C for 18 d. CTS-g-CA was enzymatically synthesized using laccase from Pleurotus ostreatus as a catalyst. The synergistic effects of CTS-g-CA treatment on mulberry fruit were evaluated using a co toxicity factor (cf). The results showed that the rotting rate of CTS-g-CA treated fruit was 37.67% (compared with that of the control at 97.67%) on day 18. The weight loss and malondialdehyde (MDA) contents of the CTS-g-CA-treated mulberry fruit were significantly lower (P < 0.05) than those of the control, CA, CTS, and CA+CTS treatments. Moreover, the DPPH and ABTS radical scavenging activities of the CTS-g-CA treatment were both higher than those of the control. Furthermore, the CTS-g-CA treatment also maintained higher levels of main active substances, such as anthocyanins, ascorbic acid, polyphenols and flavones, in mulberry fruit than the other treatments. Therefore, CTS-g-CA could be used to improve the quality and extend the shelf life of postharvest mulberry fruit during cold storage. PMID- 26992123 TI - Microfluidic Synthesis Enables Dense and Uniform Loading of Surfactant-Free PtSn Nanocrystals on Carbon Supports for Enhanced Ethanol Oxidation. AB - Developing new synthetic methods for carbon supported catalysts with improved performance is of fundamental importance in advancing proton exchange membrane fuel cell (PEMFC) technology. Continuous-flow, microfluidic reactions in capillary tube reactors are described, which are capable of synthesizing surfactant-free, ultrafine PtSn alloyed nanoparticles (NPs) on various carbon supports (for example, commercial carbon black particles, carbon nanotubes, and graphene sheets). The PtSn NPs are highly crystalline with sizes smaller than 2 nm, and they are highly dispersed on the carbon supports with high loadings up to 33 wt%. These characteristics make the as-synthesized carbon-supported PtSn NPs more efficient than state of the art commercial Pt/C catalysts applied to the ethanol oxidation reaction (EOR). Significantly enhanced mass catalytic activity (two-times that of Pt/C) and improved stability are obtained. PMID- 26992124 TI - A population-based study comparing multiple sclerosis clinic users and non-users in British Columbia, Canada. AB - BACKGROUND AND PURPOSE: Much clinical knowledge about multiple sclerosis (MS) has been gained from patients who attend MS specialty clinics. However, there is limited information about whether these patients are representative of the wider MS population. The objective of this study was to compare incident MS cases who were MS clinic users to non-users of the specialty MS clinics in British Columbia, Canada. METHODS: This was a retrospective record-linkage cohort study using prospectively collected data from the British Columbia Multiple Sclerosis database and province-wide health administrative databases. RESULTS: There were 2841 incident MS cases between 1996 and 2004 including 1648 (58%) that had registered at an MS clinic ('clinic cases') and 1193 (42%) that had not ('non clinic cases'). Gender and socioeconomic status distributions were similar; however, non-clinic cases were older, accessed health services more frequently and had a higher burden of comorbidity than clinic cases. Only 1% of the non clinic cases had filled a prescription for an MS-specific disease-modifying therapy, compared to 51% of the clinic cases. CONCLUSIONS: Our findings have several important implications: even within a publicly funded healthcare system, a high proportion of individuals with MS may not access a specialty MS clinic; the needs of MS patients managed in the community may differ from those referred to an MS clinic; findings from studies involving clinic-based MS cohorts may not always be generalizable to the wider MS population; and access to population based health administrative data offers the opportunity to gain a broader understanding of MS. PMID- 26992125 TI - Diamond-Nanoneedle-Array-Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology. AB - Vertical arrays of nanostructures can provide access to the cell cytoplasma and probe intracellular molecules. Here, the simple combination of diamond nanoneedle arrays with centrifugation-induced supergravity is shown to efficiently deliver drugs and biomaterials into the cytosol within several minutes, negotiating the endocytososomal system. The potential influence of the technique on cell metabolism is thoroughly studied. By detecting the phosphorylated histone variant H2AX (pH2AX) in the nucleus, it is proved that the operating process will not lead to DNA double-strand breaks. However, the mechanical disruption can temporarily improve the permeability of the cell membranes. Nanoneedle treatment affects cell metabolism at multiple points. The treatment can slightly elevate the apoptotic signal in A549 cells and can significantly increase the production of reactive oxygen species (ROS) in cells, particularly if combined with anticancer drugs. Meanwhile, the activity of cytosolic glucose 6-phosphate dehydrogenase (G6PD) is also raised to counterbalance the elevated ROS content. A detected depolarization of the mitochondrial membrane potential suggests mitochondrial involvement in the intracellular redox reactions and cell apoptosis which are induced by diamond nanoneedle treatment. Overall this study provides a novel understanding on the intracellular delivery mediated by nanoneedles, especially the impact on cell physiology. PMID- 26992126 TI - Influence of 5% dextrose volume on amphotericin B deoxycholate preparation. AB - OBJECTIVES: Preparation of amphotericin B deoxycholate (AmB-d) in different volumes of 5% dextrose (D5W) was studied to investigate a interesting phenomenon that AmB-d was easy to bring pipe blockage when diluted in 500 ml but not in 50 ml. METHODS: AmB-d (25 mg/vial) in 50 ml, 250 ml or 500 ml D5W was prepared. Fluids were collected before and after infusion, then were assayed by validated high-performance liquid chromatography (HPLC) method. Light obscuration assay was used to detect the particles in transfusions. KEY FINDINGS: pH values of different volumes of D5W were all about 3.7, which was lower than the requirement of AmB-d package insert (pH > 4.2). The number of insoluble particles >10 MUm/25 MUm in 25 mg/500 ml infusions exceeded China Pharmacopoeia limit. Filters in 25 mg/500 ml infusion set were full of AmB-d after dripping slowly for 6 h, and 331.3 ml solution was left in the bottles and only 11.3% of AmB-d could flow out. Whereas the AmB-d infusion consists of 25 mg/50 ml, 25 mg/250 ml and 50 mg/500 ml could meet with China Pharmacopoeia standards, and they flowed out easily and completely. CONCLUSIONS: In practice, 25 mg/250 ml and 50 mg/500 ml would be more suitable for clinical use, rather than 25 mg/500 ml. We provided a convenient method for AmB-d preparation. PMID- 26992127 TI - The modified iron avidity index: a promising phenotypic predictor in HFE-related haemochromatosis. AB - OBJECTIVE: Phenotypes of the HFE-related haemochromatosis vary considerably, making it hard to predict the course of iron accumulation. The aim of this retrospective study was to determine if the Iron Avidity Index (IAI) is a good phenotypic predictor of the number of phlebotomies needed per year during maintenance treatment (NPDMT) in patients with homozygous p.C282Y hereditary haemochromatosis (HH). METHODS: Patients with HH homozygous for p.C282Y, on maintenance treatment for at least 1 year were included. The IAI (ferritin level at diagnosis/age at diagnosis) was calculated. RESULTS: Ninety-five patients were included in the analysis. Linear regression analysis showed the confounding effect of sex on the relationship between IAI and NPDMT. A modified IAI, adjusted for sex, was calculated. As proton pump inhibitor (PPI) use was independently associated with NPDMT, the group was split in PPI- and non-PPI-users. A positive correlation between the modified IAI and the NPDMT was shown in both groups (PPI r = 0.367, P = 0.023; non-PPI r = 0.453, P < 0.001). An ROC was computed to measure the accuracy of the modified IAI to predict who needed 0-2 vs. >=3 maintenance treatments per year. The AUROC in the PPI and non-PPI group were respectively 0.576 (0.368-0.784) and 0.752 (0.606-0.899). CONCLUSION: The modified IAI is a fairly good predictor in non-PPI-using homozygous C282Y HH patients, to differentiate who needs >=3 maintenance phlebotomies per year. Therefore, this index might help to select patients that benefit from an alternative less frequent therapy, e.g. erythrocytapheresis. PMID- 26992128 TI - Growth during infancy and early childhood in children with cerebral palsy: a population-based study. AB - AIM: To describe growth in infancy and early childhood in children with cerebral palsy (CP). METHOD: One hundred and four children with CP born at minimum 36 weeks' gestation in 2002 to 2010 were included. Prospectively collected growth data were requested from public health clinics. We calculated standard deviation (SD) scores (z-scores) for weight and height for 12 set age points for each child from birth to 5 years, and for head circumference from birth to 12 months. RESULTS: Children with CP had normal growth in weight and height if they were born non-small for gestational age (non-SGA) or had mild motor impairments (i.e. Gross Motor Function Classification System [GMFCS] I-II), whereas children born SGA or with severe motor impairments (GMFCS III-V) had reduced growth (p<0.001). Children with feeding difficulties in infancy had reduced growth in weight and height throughout early childhood, while children without feeding difficulties had normal growth. Head circumference growth decreased most severely among children born SGA, who had mean z-scores of -3.0 (95% confidence interval [CI] 3.7 to -2.2) at 1 year. INTERPRETATION: Children with mild CP had normal growth in weight and height until 5 years, and in head circumference during infancy. Feeding difficulties in infancy and being born SGA were strongly associated with reduced growth. PMID- 26992129 TI - Cognitive Behavioral Therapy plus Amitriptyline for Children and Adolescents with Chronic Migraine Reduces Headache Days to <=4 Per Month. AB - OBJECTIVE: The objective of this secondary analysis of results from a previously published trial (Clinical Trials Registration Number: NCT00389038) in chronic migraine in children and adolescents was to examine if participants who received cognitive behavioral therapy and amitriptyline reached a greater level of reduction in headache frequency that no longer indicated a recommendation for preventive treatment as compared to those who received headache education and amitriptyline. BACKGROUND: Chronic migraine negatively affects children's home, school, and social activities. Preventive medication therapy is suggested for 5 or more headaches per month. Reduction to one headache day per week or less may suggest that preventive treatment is no longer indicated and provide a clinically relevant outcome for treatment efficacy and patient care. METHODS: Randomized study participants (N = 135) kept a daily record of their headache frequency during 20 weeks of treatment and during a 1 year follow-up period. Baseline headache frequency was determined at the end of a 28 day screening period. Post treatment frequency was determined at 20 weeks (N = 128 completed) and post treatment follow-up was measured 12 months later (N = 124 completed). A chi square test of independence was conducted by treatment group and by time point to determine group differences in the proportion of headache days experienced. RESULTS: At 20 weeks (post treatment), 47% of the cognitive behavioral therapy plus amitriptyline group had <=4 headache days per month compared to 20% of the headache education plus amitriptyline group, (P = .0011), and 32% of the cognitive behavioral therapy plus amitriptyline group had <=3 headache days per month at 20 weeks compared to 16% of the headache education plus amitriptyline group, (P = .0304). At the month 12 follow-up, 72% of the cognitive behavioral therapy plus amitriptyline group had <=4 headache days per month compared to 52% of the headache education plus amitriptyline group, (P = .0249), and 61% of the cognitive behavioral therapy plus amitriptyline group had <=3 headache days per month at their month 12 follow-up compared to 40% of the headache education plus amitriptyline group, (P = .0192). CONCLUSIONS: Participants who received cognitive behavioral therapy and amitriptyline were more likely than participants who received headache education plus amitriptyline to reach the clinically meaningful outcome of less than or equal to 4 headache days per month at both time points. These results may help inform what treatment outcomes are possible for children and adolescents suffering from chronic migraine and provides further evidence for behavioral treatment to be considered as a key part of a first line treatment regimen. PMID- 26992130 TI - Direct Asymmetric Reductive Amination for the Synthesis of Chiral beta Arylamines. AB - The highly efficient and direct asymmetric reductive amination of arylacetones catalyzed by an iridium complex for the preparation of enantiomerically pure beta arylamines is described. The monodentate phosphoramidite ligand exhibits superb reactivity (TONs of up to 20 000) and enantioselectivity (up to 99 % ee). Additives played important roles in this reductive coupling reaction. PMID- 26992131 TI - Properties and reactivity of nucleic acids relevant to epigenomics, transcriptomics, and therapeutics. AB - Developments in epigenomics, toxicology, and therapeutic nucleic acids all rely on a precise understanding of nucleic acid properties and chemical reactivity. In this review we discuss the properties and chemical reactivity of each nucleobase and attempt to provide some general principles for nucleic acid targeting or engineering. For adenine-thymine and guanine-cytosine base pairs, we review recent quantum chemical estimates of their Watson-Crick interaction energy, pi-pi stacking energies, as well as the nuclear quantum effects on tautomerism. Reactions that target nucleobases have been crucial in the development of new sequencing technologies and we believe further developments in nucleic acid chemistry will be required to deconstruct the enormously complex transcriptome. PMID- 26992133 TI - Lived experience of Korean nurses caring for patients on maintenance haemodialysis. AB - AIMS AND OBJECTIVES: To understand the lived experience of nurses who care for people undergoing maintenance haemodialysis. BACKGROUND: There is a lack of research regarding the lived experience of nurses caring for people undergoing chronic haemodialysis, in spite of an increased number of nurses and patients. DESIGN: A qualitative descriptive phenomenological study was conducted. METHODS: Fourteen nurses working at two haemodialysis centres in Korea were selected via purposive sampling and participated in in-depth interviews. Data were collected from October 2013-January 2014 and analysed using the phenomenological research method. RESULTS: Four themes were extracted for haemodialysis nurses' caring experience: feelings of pity for clients scheduled for haemodialysis treatment; continuous effort to establish good relationships with clients; feeling comfortable with clients, as though they were family or friends; and reflecting on their own lives through the lives of clients. CONCLUSIONS: Haemodialysis nurses experienced therapeutic relationships while taking care of clients undergoing haemodialysis; they also experienced maturation through reflection on their lives as nurses and human beings. An understanding of nurses' experiences in caring for people undergoing haemodialysis should be the basis of practice, education and nursing research in haemodialysis. RELEVANCE TO CLINICAL PRACTICE: This study could be helpful in enabling nursing students and/or nurses to understand the experience of caring and its meaning with respect to clients undergoing haemodialysis. PMID- 26992134 TI - Nursing Diagnosis Based on Signs and Symptoms of Patients With Heart Disease. AB - PURPOSE: The aim was to identify the main signs and symptoms of cardiac patients hospitalized in a unit of intensive cardiology care in order to infer the main nursing diagnoses (NDs). METHODS: We performed a cross-sectional study; the sample consisted of 77 randomly selected records. Those records included only patients hospitalized for cardiovascular causes and with electronic chart available. FINDINGS: Signs and symptoms identified at admission were psychic (40.3%), compressive dressing on arterial puncture site (33.8%), chest pain (29.9%), tachycardia (22.1%), and hemodynamic instability (20.8%). CONCLUSIONS AND PRACTICAL IMPLICATIONS: According to the data collected, we were able to infer that acute pain, excess of fluid volume, decreased cardiac output, spontaneous ventilation impaired, anxiety and impaired skin integrity are priority for the NDs in the studied population. OBJETIVO: identificar os principais sinais e sintomas de pacientes cardiacos internados em uma unidade de cuidados intensivos de cardiologia, visando inferir os diagnosticos de enfermagem prioritarios. METODO: Estudo transversal; a amostra foi composta por 77 registros selecionados aleatoriamente. Incluiram-se apenas pacientes internados por causa cardiovascular e com registro eletronico disponivel. RESULTADOS: Os sinais e sintomas identificados na admissao foram psiquicos (40,3%), curativo compressivo em sitio de puncao arterial (33,8%), dor toracica (29,9%), taquicardia (22,1%) e instabilidade hemodinamica (20,8%). CONCLUSOES E IMPLICACOES PARA A PRATICA: De acordo com os dados levantados foram inferidos Dor Aguda, Volume de Liquidos Excessivo, Debito Cardiaco Diminuido, Ventilacao Espontanea Prejudicada, Ansiedade e Integridade da Pele Prejudicada como diagnosticos de enfermagem prioritarios para a populacao estudada. PMID- 26992135 TI - Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. AB - Prion protein (PrP) protects neural cells against oxidative stress, hypoxia, ischemia, and hypoglycemia. In the present study we confirm that cultured PrP deficient neurons are more sensitive to oxidative stress than wild-type neurons and present the novel findings that wild-type, but not PrP-deficient astrocytes protect wild-type cerebellar neurons against oxidative stress and that exosomes released from stressed wild-type, but not from stressed PrP-deficient astrocytes reduce neuronal cell death induced by oxidative stress. We show that neuroprotection by exosomes of stressed astrocytes depends on exosomal PrP but not on neuronal PrP and that astrocyte-derived exosomal PrP enters into neurons, suggesting neuronal uptake of astrocyte-derived exosomes. Upon exposure of wild type astrocytes to hypoxic or ischemic conditions PrP levels in exosomes were increased. By mass spectrometry and Western blot analysis, we detected increased levels of 37/67 kDa laminin receptor, apolipoprotein E and the ribosomal proteins S3 and P0, and decreased levels of clusterin/apolipoprotein J in exosomes from wild-type astrocytes exposed to oxygen/glucose deprivation relative to exosomes from astrocytes maintained under normoxic conditions. The levels of these proteins were not altered in exosomes from stressed PrP-deficient astrocytes relative to unstressed PrP-deficient astrocytes. These results indicate that PrP in astrocytes is a sensor for oxidative stress and mediates beneficial cellular responses, e.g. release of exosomes carrying PrP and other molecules, resulting in improved survival of neurons under hypoxic and ischemic conditions. PMID- 26992132 TI - Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation. AB - The hair follicle is an ideal system to study stem cell specification and homeostasis due to its well characterized morphogenesis and stereotypic cycles of stem cell activation upon each hair cycle to produce a new hair shaft. The adult hair follicle stem cell niche consists of two distinct populations, the bulge and the more activation-prone secondary hair germ (HG). Hair follicle stem cells are set aside during early stages of morphogenesis. This process is known to depend on the Sox9 transcription factor, but otherwise the establishment of the hair follicle stem cell niche is poorly understood. Here, we show that that mutation of Foxi3, a Forkhead family transcription factor mutated in several hairless dog breeds, compromises stem cell specification. Further, loss of Foxi3 impedes hair follicle downgrowth and progression of the hair cycle. Genome-wide profiling revealed a number of downstream effectors of Foxi3 including transcription factors with a recognized function in hair follicle stem cells such as Lhx2, Runx1, and Nfatc1, suggesting that the Foxi3 mutant phenotype results from simultaneous downregulation of several stem cell signature genes. We show that Foxi3 displays a highly dynamic expression pattern during hair morphogenesis and cycling, and identify Foxi3 as a novel secondary HG marker. Absence of Foxi3 results in poor hair regeneration upon hair plucking, and a sparse fur phenotype in unperturbed mice that exacerbates with age, caused by impaired secondary HG activation leading to progressive depletion of stem cells. Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. Stem Cells 2016;34:1896-1908. PMID- 26992136 TI - Brazil nut consumption modulates Nrf2 expression in hemodialysis patients: A pilot study. AB - SCOPE: Previous studies showed that the supplementation with Brazil nut is effective in improving Se status, reduce oxidative stress, and inflammation in hemodialysis (HD) patients. As the nutritional compounds may promote the reduction of inflammation by activation of nuclear factor E2-related factor 2 (Nrf2), the aim of this pilot study was to evaluate the effects of Brazil nut supplementation on Nrf2 activation in HD patients. METHODS AND RESULTS: Thirteen HD patients received one Brazil nut supplementation per day for 3 months and were compared to 12 HD patients without supplementation. Peripheral blood mononuclear cells were isolated and processed for expression of nuclear factor kappa B, Nrf2, and NAD(P)H: quinone oxidoreductase 1 (NQO1) by quantitative real-time PCR. Plasma malondialdehyde, C-reactive protein and IL-6 levels were measured before and after supplementation. The Nrf2 expression increased and nuclear factor kappa B expression reducedpost supplementation. In addition, the cytokines and malondialdehyde levels decreased significantly. No significant alterations were found in the control group. CONCLUSION: This preliminary result indicates the effectiveness of Brazil nut supplementation on human Nrf2 activation in HD patients and could be a possible explanation for the beneficial effects of this nut as a bioactive compound. PMID- 26992137 TI - Mineralization of the transverse ligament of the atlas causing compressive radiculopathy. Resolution following odontoidectomy and atlantoaxial arthrodesis. AB - OBJECTIVE: To describe a case of a Boxer dog with radiculopathy due to mineralization of the transverse ligament of the atlas and subsequent resorption and resolution of clinical signs after atlantoaxial arthrodesis and odontoidectomy. CASE REPORT: A five-year-old neutered female Boxer dog was presented with a four-month history of cervical hyperaesthesia refractory to medical management. Neurological examination and magnetic resonance imaging indicated a diagnosis of radiculopathy due to cervical nerve root impingement by dystrophic mineralization of the transverse ligament of the atlas. Odontoidectomy was performed by a ventral approach and atlantoaxial arthrodesis was achieved with a ventral composite polymethylmethacrylate and pin fixation. RESULTS: Atlantoaxial arthrodesis and progressive resorption of the mineralization following stabilization facilitated indirect decompression. The radioclinical diagnosis and response to arthrodesis was considered analogous to retro-odontoid pannus in the human. CLINICAL RELEVANCE: A clinical condition similar to retro odontoid pannus may exist in the canine and may be amenable to atlantoaxial arthrodesis. PMID- 26992138 TI - Enolizable Carbonyls and N,O-Acetals: A Rational Approach for Room-Temperature Lewis Superacid-Catalyzed Direct alpha-Amidoalkylation of Ketones and Aldehydes. AB - An efficient catalytic room-temperature direct alpha-amidoalkylation of carbonyl donors, that is, ketones and aldehydes with unbiased N,O-acetals, is described. Sn(NTf2 )4 is an optimal catalyst to promote this challenging transformation at low loading and the reaction shows promising scope. A comprehensive and rational evaluation of this reaction has led to the establishment of an empirical scale of nucleophilic reactivity for a broad set of ketones that should be helpful in the synthetic design and development of carbonyl alpha-functionalization methods. PMID- 26992140 TI - Pre-clinical medical students' perceptions of their patient safety skills in a simulated emergency department. AB - OBJECTIVES: Patient safety has emerged as an important topic for inclusion in medical curricula. However, there is limited literature describing how medical students are taught, learn and self-assess patient safety skills. The present study aimed to seek pre-clinical medical students' perceptions of (i) their individual performance at a range of safety skills; and (ii) how they define patient safety in a simulated ED. METHODS: Data were collected in the form of questionnaire responses at the end of the Bond University Simulated ED activity in October 2014. The simulated ED is a session for pre-clinical medical students prior to their clinical rotations, aimed at preparing them for the clinical environment. Likert scale and short answer responses were used to describe students' perceptions of their safety skills and to identify themes related to patient safety. RESULTS: Seventy-eight out of 92 students completed the questionnaires (85% response rate). The majority of students thought their patients were safe from adverse events during their shift. However, students' perception of patient safety was wide-ranging and demonstrated a number of misconceptions. The most frequent strategies employed by students to ensure patient safety were asking for help from nursing staff or senior doctors, ensuring good communication with the patient and checking allergies before administering medication. CONCLUSION: Students had a favourable opinion of their own safety skills. However, answers to free text question revealed misconceptions about the nature of patient safety despite significant teaching on this topic. PMID- 26992139 TI - Influence of genetic and vintage factors in flavan-3-ol composition of grape seeds of a segregating Vitis vinifera population. AB - BACKGROUND: Flavan-3-ol compounds are important secondary metabolites which show high antioxidant activity and are responsible for bitterness and astringency of food products. The aim of this work was to evaluate the potential for selecting grape materials with higher seed flavanol content from a breeding population. The composition and content of flavan-3-ols from 151 genotypes obtained from crossing wine grape varieties was evaluated by UPLC in three consecutive years. RESULTS: Chromatograms of flavan-3-ol compounds showed the same 12 compounds for all samples, but quantitative differences were observed between genotypes as well as parental varieties. The most abundant compounds were (-)-epicatechin and (+) catechin followed by proanthocyanidins A2 and B2. Progeny showed higher values than the parental genotypes for every detected compound indicating directional transgressive segregation. With these results genotypes with as much as five times more flavanols than their parents could be identified. The year effect was significant; however, high correlations between years for each compound indicated that there is a strong genetic component in the determination of flavanol content. CONCLUSION: Higher contents of seed flavan-3-ols can be obtained by hybridisation, and those genotypes could be used for extracting healthy phytochemicals, adding value to seeds as a sub-product in wine elaboration. (c) 2016 Society of Chemical Industry. PMID- 26992141 TI - Differential contribution of Clavibacter michiganensis ssp. michiganensis virulence factors to systemic and local infection in tomato. AB - Clavibacter michiganensis ssp. michiganensis (Cmm) causes substantial economic losses in tomato production worldwide. The disease symptoms observed in plants infected systemically by Cmm are wilting and canker on the stem, whereas blister like spots develop in locally infected leaves. A wide repertoire of serine proteases and cell wall-degrading enzymes has been implicated in the development of wilt and canker symptoms. However, virulence factors involved in the formation of blister-like spots, which play an important role in Cmm secondary spread in tomato nurseries, are largely unknown. Here, we demonstrate that Cmm virulence factors play different roles during blister formation relative to wilting. Inoculation with a green fluorescent protein (GFP)-labelled Cmm382 indicates that penetration occurs mainly through trichomes. When spray inoculated on tomato leaves, the wild-type Cmm382 and Cmm100 (lacking plasmids pCM1 and pCM2) strains form blister-like spots on leaves, whereas Cmm27 (lacking the chp/tomA pathogenicity island) is non-pathogenic, indicating that plasmid-borne genes, which have a crucial role in wilting, are not required for blister formation. Conversely, mutations in chromosomal genes encoding serine proteases (chpC and sbtA), cell wall-degrading enzymes (pgaA and endX/Y), a transcriptional regulator (vatr2), a putative perforin (perF) and a putative sortase (srtA) significantly affect disease incidence and the severity of blister formation. The transcript levels of these genes, as measured by quantitative reverse transcription polymerase chain reaction, showed that, during blister formation, they are expressed early at 8-16 h after inoculation, whereas, during wilting, they are expressed after 24-72 h or expressed at low levels. Plant gene expression studies suggest that chpC is involved in the suppression of host defence. PMID- 26992142 TI - Applicability of albumin-bilirubin-based Japan integrated staging score in hepatitis B-associated hepatocellular carcinoma. AB - BACKGROUND AND AIM: The Japan Integrated Staging (JIS) for hepatocellular carcinoma (HCC) has been extensively studied in hepatitis virus C-endemic Japanese population but seldom evaluated outside Japan, while albumin-bilirubin (ALBI)-based JIS (ALBI-T) has never been externally validated. We evaluate the prognostic significance of the ALBI-T score among Chinese patients with hepatitis virus B (HBV)-related HCC, and to explore its potential therapeutic application in selecting patients for appropriate treatments in addition to the Barcelona Clinic Liver Cancer (BCLC) recommendation. METHODS: A cohort of 1222 HBV associated HCC patients was evaluated to compare the prognostic performance of JIS and ALBI-T scores by homogeneity likelihood chi-square and corrected Akaike information criterion. In the subgroup analysis of each BCLC stage, Kaplan-Meier method and log-rank statistics were used to compare overall survival of patients undergoing different treatment options. RESULTS: The ALBI-T score showed better prognostic performance than the JIS score, which were indicated by homogeneity likelihood chi-squares (ALBI-T 580.12 vs JIS 536.35) and Akaike information criteria (ALBI-T 9836.57 vs JIS 9880.23). Treatment options significantly influenced prognosis among patients of the same BCLC stage. With the use of ALBI T score 4 as the cutoff, the current study identified that a portion of patients (14.7%, 25.2% and 28.6% of BCLC stage B, C and D, respectively) undergoing unnecessary therapy without survival advantage. CONCLUSIONS: The ALBI-T score is applicable to Chinese patients with HBV-related HCC to provide reasonable prognostic information as well as potentially helping clinicians to avoid offering non-beneficial aggressive treatments. PMID- 26992143 TI - Preferences and motivations for exercise in early psychosis. PMID- 26992144 TI - Dissection of Individual Prostate Lobes in Mouse Models of Prostate Cancer to Obtain High Quality RNA. AB - Genetically engineered mouse models of prostate cancer allow for study of disease progression from localized tumor formation through distal metastasis. The anatomy of the mouse prostate differs dramatically from the human prostate, being composed of four lobe pairs (anterior, dorsal, lateral, and ventral), making the identification and dissection technically challenging. Although the entire murine prostate and surrounding tissue, including urethra, bladder, seminal vesicles, and associated adipose tissue, can be quickly dissected for en bloc analysis, it is necessary to isolate individual prostate lobes for gene expression studies elucidating the molecular mechanisms of prostate cancer. The procedure as described here includes full color images, allowing the researcher to appreciate the unique prostate morphology and tissue manipulation required to harvest individual prostate lobes. Along with removing all extraneous tissue, the procedure allows for direct comparison of the different prostate lobes by established downstream techniques. Importantly, high quality RNA required for next-generation gene expression analysis can only consistently be obtained from ventral and lateral lobes. Finally, preclinical studies using prostate targeted therapies can be monitored specifically in individual prostate lobes for histological and gene expression studies. J. Cell. Physiol. 232: 14-18, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26992145 TI - Mature T- and NK-cell non-Hodgkin lymphoma in children and young adolescents. AB - Mature T/Natural killer (NK)-cell neoplasms of children and the young adolescent population exhibit higher prevalence in Central and South American and Asian populations and many are associated with Epstein-Barr virus (EBV). They are represented in large part by extranodal T/NK cell lymphomas- nasal-type or extra nasal-type, chronic lymphoproliferative disorders of T/NK cells or chronic active EBV disease, systemic EBV-positive lymphoproliferative disorders of childhood, hydroa vacciniforme-like lymphoma, hepatosplenic T-cell lymphoma and primary cutaneous gamma/delta T-cell lymphoma among others. Many T/NK cell neoplasms in this age group are derived from cells of the innate immune system, in contrast to adults where they are predominantly from the adaptive immune system. The genetic basis of T/NK cell lymphomas in children and young adolescents remains largely unknown. Anthracycline-based regimens and haematopoietic stem cell transplants (allogeneic and autologous) are current treatment modalities, however it is anticipated that novel targeted therapeutic agents will be available in the near future. PMID- 26992146 TI - 3D Porous Sponge-Inspired Electrode for Stretchable Lithium-Ion Batteries. AB - A stretchable Li4 Ti5 O12 anode and a LiFePO4 cathode with 80% stretchability are prepared using a 3D interconnected porous polydimethylsiloxane sponge based on sugar cubes. 82% and 91% capacity retention for anode and cathode are achieved after 500 stretch-release cycles. Slight capacity decay of 6% in the battery using the electrode in stretched state is observed. PMID- 26992148 TI - Stochastic Resonance in Protein Folding Dynamics. AB - Although protein folding reactions are usually studied under static external conditions, it is likely that proteins fold in a locally fluctuating cellular environment in vivo. To mimic such behavior in in vitro experiments, the local temperature of the solvent can be modulated either harmonically or using correlated noise. In this study, coarse-grained molecular simulations are used to investigate these possibilities, and it is found that both periodic and correlated random fluctuations of the environment can indeed accelerate folding kinetics if the characteristic frequencies of the applied fluctuations are commensurate with the internal timescale of the folding reaction; this is consistent with the phenomenon of stochastic resonance observed in many other condensed-matter processes. To test this theoretical prediction, the folding dynamics of phosphoglycerate kinase under harmonic temperature fluctuations are experimentally probed using Forster resonance energy transfer fluorescence measurements. To analyze these experiments, a combination of theoretical approaches is developed, including stochastic simulations of folding kinetics and an analytical mean-field kinetic theory. The experimental observations are consistent with the theoretical predictions of stochastic resonance in phosphoglycerate kinase folding. When combined with an alternative experiment on the protein VlsE using a power spectrum analysis, elaborated in Dave et al., ChemPhysChem 2016, 10.1002/cphc.201501041, the overall data overwhelmingly point to the experimental confirmation of stochastic resonance in protein folding dynamics. PMID- 26992149 TI - Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents. AB - Cp*-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step. PMID- 26992147 TI - Monitoring Solution Structures of Peroxisome Proliferator-Activated Receptor beta/delta upon Ligand Binding. AB - Peroxisome proliferator-activated receptors (PPARs) have been intensively studied as drug targets to treat type 2 diabetes, lipid disorders, and metabolic syndrome. This study is part of our ongoing efforts to map conformational changes in PPARs in solution by a combination of chemical cross-linking and mass spectrometry (MS). To our best knowledge, we performed the first studies addressing solution structures of full-length PPAR-beta/delta. We monitored the conformations of the ligand-binding domain (LBD) as well as full-length PPAR beta/delta upon binding of two agonists. (Photo-) cross-linking relied on (i) a variety of externally introduced amine- and carboxyl-reactive linkers and (ii) the incorporation of the photo-reactive amino acid p-benzoylphenylalanine (Bpa) into PPAR-beta/delta by genetic engineering. The distances derived from cross linking experiments allowed us to monitor conformational changes in PPAR beta/delta upon ligand binding. The cross-linking/MS approach proved highly advantageous to study nuclear receptors, such as PPARs, and revealed the interplay between DBD (DNA-binding domain) and LDB in PPAR-beta/delta. Our results indicate the stabilization of a specific conformation through ligand binding in PPAR-beta/delta LBD as well as full-length PPAR-beta/delta. Moreover, our results suggest a close distance between the N- and C-terminal regions of full-length PPAR-beta/delta in the presence of GW1516. Chemical cross-linking/MS allowed us gaining detailed insights into conformational changes that are induced in PPARs when activating ligands are present. Thus, cross-linking/MS should be added to the arsenal of structural methods available for studying nuclear receptors. PMID- 26992151 TI - Comparison of batch and continuous multi-column protein A capture processes by optimal design. AB - Multi-column capture processes show several advantages compared to batch capture. It is however not evident how many columns one should use exactly. To investigate this issue, twin-column CaptureSMB, 3- and 4-column periodic counter-current chromatography (PCC) and single column batch capture are numerically optimized and compared in terms of process performance for capturing a monoclonal antibody using protein A chromatography. Optimization is carried out with respect to productivity and capacity utilization (amount of product loaded per cycle compared to the maximum amount possible), while keeping yield and purity constant. For a wide range of process parameters, all three multi-column processes show similar maximum capacity utilization and performed significantly better than batch. When maximizing productivity, the CaptureSMB process shows optimal performance, except at high feed titers, where batch chromatography can reach higher productivity values than the multi-column processes due to the complete decoupling of the loading and elution steps, albeit at a large cost in terms of capacity utilization. In terms of trade-off, i.e. how much the capacity utilization decreases with increasing productivity, CaptureSMB is optimal for low and high feed titers, whereas the 3-column process is optimal in an intermediate region. Using these findings, the most suitable process can be chosen for different production scenarios. PMID- 26992150 TI - TRAUMA EXPOSURE AND RISK OF SUICIDAL IDEATION AMONG ETHNICALLY DIVERSE ADULTS. AB - BACKGROUND: Little is known about the association between trauma exposure and suicidal ideation across racial/ethnic groups. Our study aim was to determine the association between trauma exposure and suicidal ideation in a nationally representative ethnically diverse sample of adults. METHODS: This study included 14,866 White, Hispanic, Black, and Asian participants 18 years and older involved in the Collaborate Psychiatric Epidemiology Surveys (2001-2003), comprised of three nationally representative studies (NCS-R, NSAL, and NLAAS). Lifetime history of suicidal ideation as assessed in the World Health Organization's World Mental Health Survey Initiative version of the Composite International Diagnostic Interview (WMH-CIDI). RESULTS: Of the 81% respondents who reported being exposed to trauma as assessed in the WMH-CIDI, 12.1% endorsed lifetime suicidal ideation. Additionally, of the 19% who did not report trauma, 1.1% endorsed lifetime suicidal ideation. Fully adjusted, multivariable logistic regression models revealed two traumas consistently associated with significantly higher odds for suicidal ideation across all four racial groups examined: Assaultive/interpersonal violence and child maltreatment. Asians, in particular, had the highest likelihood for suicidal ideation in both trauma categories, with a near threefold increased odds for assaultive/interpersonal violence exposure (OR: 2.56; 95% CI: 1.71-3.83) and nearly ninefold increased odds for child maltreatment exposure (OR: 8.43; 95% CI: 4.91-14.49). DISCUSSION: Suicidal ideation in racially/ethnically diverse American adults is strongly associated with assaultive/interpersonal violence and child maltreatment, independent of PTSD, MDD, and substance use. These findings highlight the need for monitoring of suicidal behavior following assaultive/interpersonal trauma and child maltreatment, regardless of the presence of a psychiatric disorder. PMID- 26992152 TI - An ex vivo study of photobiostimulation in the treatment of skin pathologies. AB - Photodynamic therapy (PDT) and low level laser therapy (LLLT) may mutually improve the outcomes on the healing process of chronic wounds and other skin pathologies, through processes known to stimulate the proliferation of dermal cellular structures, as well as antimicrobial application. This study proposes the use of nanoemulsion containing aluminium phthalocyanine chloride (ClAlPc) as photosensitizer (PS), to establish the most appropriate protocol for photostimulation in human skin biopsies, associated to type I collagen and elastin production. The combined effect of PS and light (diode laser at 670 nm) at three different doses is compared to the effect of light itself at doses of 70, 140 and 700 mJ c cm-2 , 7 and 14 days after irradiation. Histological analysis reveals the increase in collagen and elastin, higher than 20%, 14 days after treatment with PS and light at 140 mJ c cm-2 . Higher doses of light promote an inhibitory effect, leading to tissue degradation. In addition, the expression levels of the enzymes MMP-2 and MMP-9 (Gelatinases A and B - participant in various processes including tumoral progression and wound healing) are detected by gelatin zymography, reinforcing the efficacy of the combined treatment with PS and light at the intermediate dose. PMID- 26992153 TI - Membrane dynamics in mammalian embryogenesis: Implication in signal regulation. AB - Eukaryotes have evolved an array of membrane compartments constituting secretory and endocytic pathways that allow the flow of materials. Both pathways perform important regulatory roles. The secretory pathway is essential for the production of extracellular, secreted signal molecules, but its function is not restricted to a mere route connecting intra- and extracellular compartments. Post translational modifications also play an integral function in the secretory pathway and are implicated in developmental regulation. The endocytic pathway serves as a platform for relaying signals from the extracellular stimuli to intracellular mediators, and then ultimately inducing signal termination. Here, we discuss recent studies showing that dysfunction in membrane dynamics causes patterning defects in embryogenesis and tissue morphogenesis in mammals. PMID- 26992154 TI - Cataract surgery in children with buphthalmos. PMID- 26992155 TI - Open Label Trial of Add on Lacosamide Versus High Dose Levetiracetam Monotherapy in Patients With Breakthrough Seizures. AB - OBJECTIVES: In patients who do not achieve seizure freedom on low-dose first-line monotherapy antiepileptic drug (AED), the current practice is to increase the AED to higher doses. For patients who fail low dose levetiracetam (LEV), a reasonable alternative to increasing dosage may be the addition of a low-dose adjunctive AED. METHODS: In this open-label, pilot trial, low-dose lacosamide (200 mg/d) was added to adult patients with breakthrough seizures on low-dose monotherapy LEV (<=1500 mg/d). Comparison was made with a retrospective historical control cohort in whom the dose of LEV was raised after a breakthrough seizure. The main objectives were to determine efficacy effect size and tolerability. RESULTS: Twenty patients were recruited in the prospective polytherapy cohort, of whom 19 received at least 1 dose of adjunctive AED; the monotherapy cohort consisted of 36 patients. Six-month seizure freedom was achieved in 9 of 19 patients in the polytherapy cohort and in 15 of 36 patients in the monotherapy cohort (hazard ratio for seizure occurrence for polytherapy relative to monotherapy was 0.76; 95% confidence interval, 0.35-1.65; P = 0.49). There were treatment emergent adverse effects in 11 patients (61.1%) in the polytherapy cohort and 26 (72.2%) in the monotherapy cohort. Greater number of patients in the monotherapy cohort experienced irritability/depression (33.3% vs 5.6%, P < 0.05). CONCLUSIONS: Low dose polytherapy with LEV and lacosamide was well tolerated and efficacious. Further studies are needed to determine whether this is a reasonable alternative to high-dose LEV monotherapy. PMID- 26992156 TI - Polypharmacy in Maintenance of Bipolar Disorder. AB - OBJECTIVES: To track the outcomes of bipolar patients who had remitted from an acute manic episode on single- and multiple-drug regimens including lithium (LI), valproate (VPA), and carbamazepine (CBZ), in order to compare relapse rates on 1, 2, or 3 medications. METHODS: Following treatment of an acute manic episode and a 1-month period of no signs of mood episodes, patients were evaluated at 1- to 2 month intervals as to the kind of regimen required to maintain their stability while continuing on this regimen for 2 years. Medication regimens included 1, 2, or 3 of the following drugs: LI, VPA, and/or CBZ. The 3 medication groups were followed from entry into the study through 3 possible end points based on the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition checklist: "NO-Relapse," "Relapse," or "Dropped out." RESULTS: Of the 1312 patients included in the study and followed up for 2 years, 281 patients (21.4%) were maintained on a single drug (LI, VPA, or CBZ), 852 (65%) on 2 drugs, and 179 (13.6%) on 3 or more drugs. A smaller percentage of patients on 1 medication had NO-Relapse for 2 years (22.8%), compared with patients on 2 medications (43.9%) and patients on 3 or more medications (41.9%): chi2 = 40.3, P < 0.001. CONCLUSIONS: This study showed that overall, of the bipolar patients who were asymptomatic at 1 month, a smaller percentage of patients on 1 medication continued to be stable for 2 years, compared with patients on 2 medications and patients on 3 or more medications. PMID- 26992157 TI - The Efficacy of Gabapentin in the Treatment of Pain Due to Far Lateral Lumbar Disc Herniations. AB - OBJECTIVES: Far lateral lumbar disc herniations (FLLDHs) can cause difficulty and differences in diagnosis and treatment compared with intraspinal herniation. We have aimed to analyze the efficacy of gabapentin as a noninvasive treatment of pain in patients with isolated FLLDH. METHODS: Thirteen patients with isolated FLLDH were evaluated for the study prospectively. All of the cases were diagnosed by lumbar magnetic resonance imaging. The previously prescribed medical therapy of the patients was not changed and gabapentin (3 * 600 mg/d) was added. For each patient, visual analog scale and Odom criteria were administered and recorded at 4 time points as follows: pretreatment and days 1, 7, and 30 posttreatment. Paired t test was used to examine scores of the cases before and after gabapentin treatment. Results were considered significant at P < 0.05, and 95% confidence interval was calculated. RESULTS: Mean visual analog scale score was 9.3 in the pretreatment period, and reduced to 5, 2.6, and 1.3 on posttreatment days 1, 7, and 30, respectively (P < 0.05). Mean Odom criteria score was 4 before gabapentin treatment. It decreased to 2.3 at posttreatment day 1 and 1.5 at day 7. At the end of 1 month, symptoms had resolved completely in all cases (P < 0.05). CONCLUSIONS: Gabapentin provided fast and effective relief of pain caused by FLLDH. We advise that the gabapentin should be kept in mind in the first-step medication of pain for such patients. Direct compression of the dorsal root ganglion or its distal part may be related to the intense pain-relief effect provided by gabapentin. PMID- 26992159 TI - Child maltreatment - prevalence and characteristics of mandatory reports from dental professionals to the social services. AB - BACKGROUND: Dental professionals are required to report suspicions of child maltreatment to the social services. As yet, no studies assess the prevalence of these mandated reports from dental care services or their content. AIM: This study investigates the prevalence and characteristics of mandated reports from dental professionals to the social services. Furthermore, it analyses associations between dental professionals reporting suspicions of maltreatment with such reports from other sources. DESIGN: The study collected dental mandatory reports from within one municipality of Sweden during 2008-2014. The material consisted of a total of 147 reports by dental professionals regarding 111 children. RESULTS: The total prevalence of reports from dental care services to the social services was 1.5 per 1000 children with a significant increase between 2008 and 2011 (P < 0.001). The primary cause for a report concerned parental deficiencies in care (n = 93) and secondly, a concern for dental neglect (n = 52) (P < 0.001). Among all reports, 86% involved children with prior contacts with the social services. CONCLUSION: Reports to the social services from dental care services on suspicions of child maltreatment concern parental deficiencies (failure to attend appointments) and neglect (dental neglect). Mandated reports from dental care services often co-occur with other mandated reports. PMID- 26992158 TI - Risperidone-Induced Nocturnal Enuresis Successfully Treated With Reboxetine. AB - There are few reports in the literature and scarce research on the topic and the treatment of antipsychotic medication-induced urinary incontinence or nocturnal enuresis (NE) despite the significant frequency of these adverse effects.Treatment for antipsychotic medication-induced urinary incontinence has been reported in relation to clozapine with response to numerous pharmacological strategies such as ephedrine, oxybutynin, intranasal desmopressin, trihexyphenidyl, and amitriptyline.We report a case of NE induced by risperidone which has been successfully treated with reboxetine.To the best of our knowledge, this article is the first report of an atypical antipsychotic medication-induced NE treated with reboxetine.Reboxetine may be an effective treatment for risperidone-induced NE. Further research is required to confirm our finding and apply this treatment for NE caused by other neuroleptics. PMID- 26992160 TI - Diabetes risk prediction model for non-obese Asian Indians residing in North India using cut-off values for pancreatic and intra-abdominal fat volume and liver span. PMID- 26992162 TI - Radiological imaging in all stage III melanoma: current practice in the U.K. PMID- 26992161 TI - Postnatal microcephaly and pain insensitivity due to a de novo heterozygous DNM1L mutation causing impaired mitochondrial fission and function. AB - An emerging class of mitochondrial disorders is caused by mutations in nuclear genes affecting mitochondrial dynamics and function. One of these is the DNM1L gene encoding the dynamin-related protein 1 (DRP1), which is pivotal in the mitochondrial fission process. Here, we describe a patient with a novel dominant negative, de novo DNM1L mutation, which expands the clinical spectrum. The patient reported here exhibits a chronic neurological disorder, characterized by postnatal microcephaly, developmental delay, and pain insensitivity. Muscle biopsy disclosed decreased respiratory chain complex IV activity. Exome sequencing showed a de novo heterozygous c.1084G>A (p.G362S) mutation. Subsequent studies of patient skin fibroblasts showed markedly impaired mitochondrial fission and a partial respiratory chain defect while peroxisomal morphology remained intact. Human foreskin fibroblasts over-expressing the mutant DNM1L gene displayed aberrant mitochondrial morphology. (c) 2016 Wiley Periodicals, Inc. PMID- 26992163 TI - A Portable Sensory Augmentation Device for Balance Rehabilitation Using Fingertip Skin Stretch Feedback. AB - Neurological disorders are the leading causes of poor balance. Previous studies have shown that biofeedback can compensate for weak or missing sensory information in people with sensory deficits. These biofeedback inputs can be easily recognized and converted into proper information by the central nervous system (CNS), which integrates the appropriate sensorimotor information and stabilizes the human posture. In this study, we proposed a form of cutaneous feedback which stretches the fingertip pad with a rotational contactor, so-called skin stretch. Skin stretch at a fingertip pad can be simply perceived and its small contact area makes it favored for small wearable devices. Taking advantage of skin stretch feedback, we developed a portable sensory augmentation device (SAD) for rehabilitation of balance. SAD was designed to provide postural sway information through additional skin stretch feedback. To demonstrate the feasibility of the SAD, quiet standing on a force plate was evaluated while sensory deficits were simulated. Fifteen healthy young adults were asked to stand quietly under six sensory conditions: three levels of sensory deficits (normal, visual deficit, and visual + vestibular deficits) combined with and without augmented sensation provided by SAD. The results showed that augmented sensation via skin stretch feedback helped subjects correct their posture and balance, especially as the deficit level of sensory feedback increased. These findings demonstrate the potential use of skin stretch feedback in balance rehabilitation. PMID- 26992165 TI - MALDI mass spectrometry imaging of N-glycans on tibial cartilage and subchondral bone proteins in knee osteoarthritis. AB - Magnetic resonance imaging (MRI) is a non-invasive technique routinely used to investigate pathological changes in knee osteoarthritis (OA) patients. MRI uniquely reveals zones of the most severe change in the subchondral bone (SCB) in OA, called bone marrow lesions (BMLs). BMLs have diagnostic and prognostic significance in OA, but MRI does not provide a molecular understanding of BMLs. Multiple N-glycan structures have been observed to play a pivotal role in the OA disease process. We applied matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) of N-glycans to formalin-fixed paraffin-embedded (FFPE) SCB tissue sections from patients with knee OA, and liquid chromatography electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was conducted on consecutive sections to structurally characterize and correlate with the N glycans seen by MALDI-MSI. The application of this novel MALDI-MSI protocol has enabled the first steps to spatially investigate the N-glycome in the SCB of knee OA patients. PMID- 26992166 TI - Serum Phosphorus Concentration and Coronary Artery Calcification in Subjects without Renal Dysfunction. AB - Serum phosphorus (P) concentration is associated with coronary artery calcification (CAC) as well as cardiovascular events in patients with chronic kidney disease. It has been suggested that this relationship is extended to subjects without renal dysfunction, but further explorations in diverse races and regions are still needed. We performed a cross-sectional study of 2,509 Korean subjects (Far Eastern Asian) with an estimated glomerular filtration rate of >=60 ml/min/1.73 m2 and who underwent coronary computerized tomography. Serum P concentration was divided into pre-determined 4 categories: <=3.2, 3.2< to <=3.6, 3.6< to <=4.0 and >4.0 mg/dL. Agatston score (AS), an index of CAC, was divided into 3 categories: 0, 0< to <=100, and >100. A multinomial logit model (baseline outcome: AS = 0) was applied to estimate the odds ratio (OR) for each serum P category (reference: <=3.2mg/dL). Mean age of subjects was 53.5+/-9.1 years and 36.9% were female. In the adjusted model, serum P concentration of 3.6< to <=4.0 mg/dL and >4.0 mg/dL showed high ORs for AS of >100 [OR: 1.58, 95% confidence interval (CI): 1.04-2.40 and OR: 2.11, 95% CI: 1.34-3.32, respectively]. A unit (mg/dL) increase in serum P concentration was associated with 50% increase in risk of AS >100 (OR: 1.50, 95% CI: 1.16-1.94). A higher serum P concentration, even within a normal range, may be associated with a higher CAC in subjects with normal renal function. PMID- 26992167 TI - Disturbed Experience of Self: Psychometric Analysis of the Self-Experience Lifetime Frequency Scale (SELF). AB - BACKGROUND: Schizophrenia is characterized by positive and negative symptoms, but recently anomalous self-experiences, e.g. exaggerated self-consciousness (hyperreflectivity), receive more attention as an important symptom domain in schizophrenia patients. The semi-structured interview, the Examination of Anomalous Self-Experience (EASE) [Psychopathology 2005;38:236-258], examines experiences of a disturbed sense of self in a sophisticated but time-consuming manner. Therefore, we proposed the Self-Experience Lifetime Frequency scale (SELF), an instrument intended to screen for self-disturbance phenomena. Here we compared scores of patients, their siblings and healthy controls on the SELF. Methods and Sampling: The SELF is composed of a validated screener for symptoms of depersonalization complemented by questions covering several other domains of self-disturbance. A total of 426 patients with a psychotic disorder, 526 of their unaffected siblings, and 297 healthy controls completed the SELF. Patients' scores on the 12 items of the SELF were subjected to an explorative principal axis factor analysis (PAF); composite scores on factor components were compared between the three participant groups. RESULTS: The PAF revealed two components, explaining 43.9 and 9.5% of variance, respectively. The first component represents a disturbance of self-awareness; the second component reflects (milder forms of) diminished self-affection or depersonalization. The two components of the SELF revealed good internal consistency (component 1, alpha = 0.88; component 2, alpha = 0.79; x03C1; = 0.85). Patients showed significantly higher scores on both factor components in comparison with both siblings and controls. No significant differences were found between siblings and controls. CONCLUSIONS: The findings of the current study suggest that the SELF comprises two components of self-disturbance. Patients reported more (severe) symptoms of self-disturbance on both components, suggesting that it is feasible to screen for self-disturbance phenomena in patients with psychotic disorders with the SELF. Screening for symptoms of self-disturbance is important since these symptoms are associated with suffering and, moreover, these phenomena may mark the transition from intact to aberrant reality testing. PMID- 26992168 TI - The Description of Shale Reservoir Pore Structure Based on Method of Moments Estimation. AB - Shale has been considered as good gas reservoir due to its abundant interior nanoscale pores. Thus, the study of the pore structure of shale is of great significance for the evaluation and development of shale oil and gas. To date, the most widely used approaches for studying the shale pore structure include image analysis, radiation and fluid invasion methods. The detailed pore structures can be studied intuitively by image analysis and radiation methods, but the results obtained are quite sensitive to sample preparation, equipment performance and experimental operation. In contrast, the fluid invasion method can be used to obtain information on pore size distribution and pore structure, but the relative simple parameters derived cannot be used to evaluate the pore structure of shale comprehensively and quantitatively. To characterize the nanoscale pore structure of shale reservoir more effectively and expand the current research techniques, we proposed a new method based on gas adsorption experimental data and the method of moments to describe the pore structure parameters of shale reservoir. Combined with the geological mixture empirical distribution and the method of moments estimation principle, the new method calculates the characteristic parameters of shale, including the mean pore size (mean), standard deviation (sigma), skewness (Sk) and variation coefficient (c). These values are found by reconstructing the grouping intervals of observation values and optimizing algorithms for eigenvalues. This approach assures a more effective description of the characteristics of nanoscale pore structures. Finally, the new method has been applied to analyze the Yanchang shale in the Ordos Basin (China) and Longmaxi shale from the Sichuan Basin (China). The results obtained well reveal the pore characteristics of shale, indicating the feasibility of this new method in the study of the pore structure of shale reservoir. PMID- 26992169 TI - Predators Exacerbate Competitive Interactions and Dominance Hierarchies between Two Coral Reef Fishes. AB - Predation and competition are critical processes influencing the ecology of organisms, and can play an integral role in shaping coral reef fish communities. This study compared the relative and interacting effects of competition and predation on two competing species of coral reef fish, Pomacentrus amboinensis and P. moluccensis (Pomacentridae), using a multifactorial experiment. Fish were subjected to the sight and smell of a known predator (Pseudochromis fuscus), the presence of the heterospecific competitor (i.e., P. amboinensis vs. P. moluccensis), or a combination of the two for a period of 19 days. The sub-lethal effects of predator/competitor treatments were compared with controls; a combination of otolith microstructure analysis and observations were used to determine otolith growth patterns and behaviour. We predicted that the stress of competition and/or predation would result in strong sub-lethal impacts, and act synergistically on growth and behavioural patterns. We found strong evidence to support this prediction, but only for P. amboinensis, which suffered reductions in growth in both predator and competitor treatments, with the largest reductions occurring when subjected to both predation and competition concurrently. There was strong evidence of asymmetrical competition between the two damselfish species, with P. moluccensis as the dominant competitor, displaying strong aggressive behaviour towards P. amboinensis. Growth reductions for P. amboinensis in predator/competitor treatments appeared to come about primarily due to increases in shelter seeking behaviour, which significantly reduced the foraging rates of individuals compared with controls. These data highlight the importance of predator/competitor synergisms in influencing key behaviours and demographic parameters for juvenile coral reef fishes. PMID- 26992170 TI - Brief Report: Association of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome With Gonosomal Mosaicism of a Novel 24-Nucleotide TNFRSF1A Deletion. AB - OBJECTIVE: To investigate the molecular cause of persistent fevers in a patient returning from working overseas, in whom investigations for tropical diseases yielded negative results. METHODS: DNA was extracted from the patient's whole blood, leukocyte subpopulations, saliva, hair root, and sperm. The TNFRSF1A gene was analyzed by polymerase chain reaction (PCR), allele-specific PCR, Sanger sequencing, and next-generation sequencing. In silico molecular modeling was performed to predict the structural and functional consequences of the tumor necrosis factor receptor (TNFR) type I protein mutation in the extracellular domain. RESULTS: Sanger sequencing corroborated by allele-specific PCR detected a novel in-frame deletion of 24 nucleotides (c.255_278del) in the TNFRSF1A gene, and this was subsequently confirmed using next-generation sequencing methods (targeted sequencing and amplicon-based deep sequencing). Results of amplicon based deep sequencing revealed variable frequency of the mutant allele among different cell lines, including sperm, thus supporting the presence of gonosomal TNFRSF1A mosaicism. The patient had a complete response to treatment with interleukin-1 (IL-1) blockade, with resolution of symptoms and normalization of acute-phase protein levels. CONCLUSION: We describe the first case of gonosomal TNFRSF1A mosaicism in a patient with TNFR-associated periodic syndrome (TRAPS), which was attributable to a novel, somatic 24-nucleotide in-frame deletion. The clinical picture in this patient, including the complete response to IL-1 blockade, was typical of that found in TRAPS. This case adds TRAPS to the list of dominantly inherited autoinflammatory diseases reported to be caused by somatic (or postzygotic) mutation. PMID- 26992173 TI - Computational materials design of crystalline solids. AB - The modelling of materials properties and processes from first principles is becoming sufficiently accurate as to facilitate the design and testing of new systems in silico. Computational materials science is both valuable and increasingly necessary for developing novel functional materials and composites that meet the requirements of next-generation technology. A range of simulation techniques are being developed and applied to problems related to materials for energy generation, storage and conversion including solar cells, nuclear reactors, batteries, fuel cells, and catalytic systems. Such techniques may combine crystal-structure prediction (global optimisation), data mining (materials informatics) and high-throughput screening with elements of machine learning. We explore the development process associated with computational materials design, from setting the requirements and descriptors to the development and testing of new materials. As a case study, we critically review progress in the fields of thermoelectrics and photovoltaics, including the simulation of lattice thermal conductivity and the search for Pb-free hybrid halide perovskites. Finally, a number of universal chemical-design principles are advanced. PMID- 26992174 TI - A Simple, Fast, Filter-Based Algorithm for Approximate Circular Pattern Matching. AB - This paper deals with the approximate version of the circular pattern matching (ACPM) problem, which appears as an interesting problem in many biological contexts. The circular pattern matching problem consists in finding all occurrences of the rotations of a pattern P of length m in a text T of length n. In ACPM, we consider occurrences with k -mismatches under the Hamming distance model. In this paper, we present a simple and fast filter-based algorithm to solve the ACPM problem. We compare our algorithm with the state of the art algorithms and the results are found to be excellent. In particular, our algorithm runs almost twice as fast than the state of the art. Much of the efficiency of our algorithm can be attributed to its filters that are effective but extremely simple and lightweight. PMID- 26992171 TI - Methods for Isolation and Purification of Murine Liver Sinusoidal Endothelial Cells: A Systematic Review. AB - To study the biological functions of liver sinusoidal endothelial cells (LSEC) and to identify their interplay with blood or liver cells, techniques allowing for the isolation and purification of LSEC have been developed over the last decades. The objective of the present review is to summarize and to compare the efficiency of existing methods for isolating murine LSEC. Toward this end, the MEDLINE database was searched for all original articles describing LSEC isolation from rat and mouse livers. Out of the 489 publications identified, 23 reported the main steps and outcomes of the procedure and were included in our review. Here, we report and analyse the technical details of the essential steps of the techniques used for LSEC isolation. The correlations between the prevalence of some steps and the efficiency of LSEC isolation were also identified. We found that centrifugal elutriation, selective adherence and, more recently, magnetic activated cell sorting were used for LSEC purification. Centrifugal elutriation procured high yields of pure LSEC (for rats 30-141.9 million cells for 85-98% purities; for mice 9-9.25 million cells for >95% purities), but the use of this method remained limited due to its high technical requirements. Selective adherence showed inconsistent results in terms of cell yields and purities in rats (5-100 million cells for 73.7-95% purities). In contrast, magnetic-activated cell sorting allowed for the isolation of highly pure LSEC, but overall lower cell yields were reported (for rats 10.7 million cells with 97.6% purity; for mice 0.5-9 million cells with 90-98% purities). Notably, the controversies regarding the accuracy of several phenotypic markers for LSEC should be considered and their use for both magnetic sorting and characterization remain doubtful. It appears that more effort is needed to refine and standardize the procedure for LSEC isolation, with a focus on the identification of specific antigens. Such a procedure is required to identify the molecular mechanisms regulating the function of LSEC and to improve our understanding of their role in complex cellular processes in the liver. PMID- 26992172 TI - Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids. AB - Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1) was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection. PMID- 26992175 TI - Eligibility of Outpatient Spine Surgery Candidates in a Single Private Practice. AB - STUDY DESIGN: Level III. PURPOSE: To retrospectively review the eligibility of surgical patients meeting predetermined outpatient surgery criteria in a single surgeon private practice. SUMMARY OF BACKGROUND DATA: There is a burgeoning awareness among patients, surgeons, and insurers of the cost benefits and safety of outpatient spine surgeries. At the end of 2014, Centers for Medicare & Medicaid Services have released its final 2015 payment rules and codes for spinal decompression and fusion. This move confirms the safety of procedures being performed in the ambulatory surgery centers (ASCs). METHODS: We conducted a database review between 2008 and 2014 and identified 1625 orthopedic procedures. All nonsurgical spine procedures were excluded from the study. Eligibility for outpatient spine surgery was based on criteria generated from a combination of published standard of care for major operations and the chief surgeon's experience. A matched cohort based on type of surgery in each facility of all spine surgery patients was created, group 1 (hospital patients) and group 2 (ASC patients). RESULTS: A total of 708 patients underwent spinal surgery during this time period with a 53% female population. A total of 557 of 708 (79%) patients were eligible for outpatient spine surgery. There were 210 surgical procedures in group 1 (inpatient) comprised of 72 decompression and 138 fusion procedures. In group 2 (outpatient), there were 347 procedures made up of 150 patients undergoing decompression and 197 undergoing fusion or disc replacement. To confirm that hospital procedures are eligible to be performed in the ASC, the chi test was performed. We found that ASC-eligible hospital patients can indeed be done in an ASC (P=0.037). CONCLUSIONS: Outpatient spine surgery is feasible in 79% of patients in this single-surgeon private practice. On the basis of these results, a majority of spine procedures can be performed in an outpatient setting following our eligibility criteria. PMID- 26992176 TI - Building Ancestral Recombination Graphs for Whole Genomes. AB - We propose a heuristic algorithm, called ARG4WG, to build plausible ancestral recombination graphs (ARGs) from thousands of whole genome samples. By using the longest shared end for recombination inference, ARG4WG constructs ARGs with small numbers of recombination events that perform well in association mapping on genome-wide association studies. PMID- 26992177 TI - An IR-Based Approach Utilizing Query Expansion for Plagiarism Detection in MEDLINE. AB - The identification of duplicated and plagiarized passages of text has become an increasingly active area of research. In this paper, we investigate methods for plagiarism detection that aim to identify potential sources of plagiarism from MEDLINE, particularly when the original text has been modified through the replacement of words or phrases. A scalable approach based on Information Retrieval is used to perform candidate document selection-the identification of a subset of potential source documents given a suspicious text-from MEDLINE. Query expansion is performed using the ULMS Metathesaurus to deal with situations in which original documents are obfuscated. Various approaches to Word Sense Disambiguation are investigated to deal with cases where there are multiple Concept Unique Identifiers (CUIs) for a given term. Results using the proposed IR based approach outperform a state-of-the-art baseline based on Kullback-Leibler Distance. PMID- 26992178 TI - Super-Thresholding: Supervised Thresholding of Protein Crystal Images. AB - In general, a single thresholding technique is developed or enhanced to separate foreground objects from background for a domain of images. This idea may not generate satisfactory results for all images in a dataset, since different images may require different types of thresholding methods for proper binarization or segmentation. To overcome this limitation, in this study, we propose a novel approach called "super-thresholding" that utilizes a supervised classifier to decide an appropriate thresholding method for a specific image. This method provides a generic framework that allows selection of the best thresholding method among different thresholding techniques that are beneficial for the problem domain. A classifier model is built using features extracted priori from the original image only or posteriori by analyzing the outputs of thresholding methods and the original image. This model is applied to identify the thresholding method for new images of the domain. We performed our method on protein crystallization images, and then we compared our results with six thresholding techniques. Numerical results are provided using four different correctness measurements. Super-thresholding outperforms the best single thresholding method around 10 percent, and it gives the best performance for protein crystallization dataset in our experiments. PMID- 26992179 TI - Mapping Temporal Variables Into the NeuCube for Improved Pattern Recognition, Predictive Modeling, and Understanding of Stream Data. AB - This paper proposes a new method for an optimized mapping of temporal variables, describing a temporal stream data, into the recently proposed NeuCube spiking neural network (SNN) architecture. This optimized mapping extends the use of the NeuCube, which was initially designed for spatiotemporal brain data, to work on arbitrary stream data and to achieve a better accuracy of temporal pattern recognition, a better and earlier event prediction, and a better understanding of complex temporal stream data through visualization of the NeuCube connectivity. The effect of the new mapping is demonstrated on three benchmark problems. The first one is the early prediction of patient sleep stage event from temporal physiological data. The second one is the pattern recognition of dynamic temporal patterns of traffic in the Bay Area of California and the last one is the Challenge 2012 contest data set. In all the cases, the use of the proposed mapping leads to an improved accuracy of pattern recognition and event prediction and a better understanding of the data when compared with traditional machine learning techniques or SNN reservoirs with an arbitrary mapping of the variables. PMID- 26992180 TI - Use of Cervical Pessary in the Management of Cervical Insufficiency. AB - Prevention of spontaneous preterm birth is an important public health priority. Pessary may be a potential therapy in cases of cervical insufficiency, in singleton and multiple gestations. Availability of transvaginal sonography for accurate assessment of cervical length is allowing for the tailoring of therapy to a more specific subset of patients who may benefit from this treatment. Pessary therapy is attractive given the favorable side effect profile, low cost, and ease of placement and removal. Large randomized trials are ongoing to validate initial favorable findings. PMID- 26992181 TI - Foreword. PMID- 26992182 TI - Mammographic Breast Density and Breast Cancer Risk: Implications of the Breast Density Legislation for Health Care Practitioners. AB - Breast density has emerged as a critical phenotypic marker of increased breast cancer risk. The breast density legislation, passed in multiple states, requires patient notification of the implications of the breast density on breast cancer risk and screening. Supplemental screening may be suggested in the state regulation; however, there are limited data to guide conversations with patients. This article will review the current state of supplemental screening in women with dense breasts and discuss theories of the mechanism of action. Guidance is provided to assist in shared decision making and appropriate patient counseling. PMID- 26992183 TI - An Energy-Efficient Target-Tracking Strategy for Mobile Sensor Networks. AB - In this paper, an energy-efficient strategy is proposed for tracking a moving target in an environment with obstacles, using a network of mobile sensors. Typically, the most dominant sources of energy consumption in a mobile sensor network are sensing, communication, and movement. The proposed algorithm first divides the field into a grid of sufficiently small cells. The grid is then represented by a graph whose edges are properly weighted to reflect the energy consumption of sensors. The proposed technique searches for near-optimal locations for the sensors in different time instants to route information from the target to destination, using a shortest path algorithm. Simulations confirm the efficacy of the proposed algorithm. PMID- 26992185 TI - An Efficient Method for Traffic Sign Recognition Based on Extreme Learning Machine. AB - This paper proposes a computationally efficient method for traffic sign recognition (TSR). This proposed method consists of two modules: 1) extraction of histogram of oriented gradient variant (HOGv) feature and 2) a single classifier trained by extreme learning machine (ELM) algorithm. The presented HOGv feature keeps a good balance between redundancy and local details such that it can represent distinctive shapes better. The classifier is a single-hidden-layer feedforward network. Based on ELM algorithm, the connection between input and hidden layers realizes the random feature mapping while only the weights between hidden and output layers are trained. As a result, layer-by-layer tuning is not required. Meanwhile, the norm of output weights is included in the cost function. Therefore, the ELM-based classifier can achieve an optimal and generalized solution for multiclass TSR. Furthermore, it can balance the recognition accuracy and computational cost. Three datasets, including the German TSR benchmark dataset, the Belgium traffic sign classification dataset and the revised mapping and assessing the state of traffic infrastructure (revised MASTIF) dataset, are used to evaluate this proposed method. Experimental results have shown that this proposed method obtains not only high recognition accuracy but also extremely high computational efficiency in both training and recognition processes in these three datasets. PMID- 26992186 TI - Semi-Supervised Image-to-Video Adaptation for Video Action Recognition. AB - Human action recognition has been well explored in applications of computer vision. Many successful action recognition methods have shown that action knowledge can be effectively learned from motion videos or still images. For the same action, the appropriate action knowledge learned from different types of media, e.g., videos or images, may be related. However, less effort has been made to improve the performance of action recognition in videos by adapting the action knowledge conveyed from images to videos. Most of the existing video action recognition methods suffer from the problem of lacking sufficient labeled training videos. In such cases, over-fitting would be a potential problem and the performance of action recognition is restrained. In this paper, we propose an adaptation method to enhance action recognition in videos by adapting knowledge from images. The adapted knowledge is utilized to learn the correlated action semantics by exploring the common components of both labeled videos and images. Meanwhile, we extend the adaptation method to a semi-supervised framework which can leverage both labeled and unlabeled videos. Thus, the over-fitting can be alleviated and the performance of action recognition is improved. Experiments on public benchmark datasets and real-world datasets show that our method outperforms several other state-of-the-art action recognition methods. PMID- 26992188 TI - Disturbance Observer-Based Fuzzy Control of Uncertain MIMO Mechanical Systems With Input Nonlinearities and its Application to Robotic Exoskeleton. AB - We develop a novel disturbance observer-based adaptive fuzzy control approach in this paper for a class of uncertain multi-input-multi-output mechanical systems possessing unknown input nonlinearities, i.e., deadzone and saturation and time varying external disturbance. It is shown that the input nonlinearities can be represented by a nominal part and a nonlinear disturbance term. High-dimensional integral-type Lyapunov function is used to construct the controller. Fuzzy logic system is employed to cancel model uncertainties, and disturbance observer is also integrated into control design to compensate the fuzzy approximation error, external disturbance, and nonlinear disturbance caused by the unknown input nonlinearities. Semiglobally uniformly ultimately boundness of the closed-loop control system is guaranteed with tracking errors keeping bounded. Experimental studies on a robotic exoskeleton using the proposed control demonstrate the effectiveness of the approach. PMID- 26992190 TI - Adaptive Fuzzy Output-Feedback Stabilization Control for a Class of Switched Nonstrict-Feedback Nonlinear Systems. AB - This paper proposes an fuzzy adaptive output-feedback stabilization control method for nonstrict feedback uncertain switched nonlinear systems. The controlled system contains unmeasured states and unknown nonlinearities. First, a switched state observer is constructed in order to estimate the unmeasured states. Second, a variable separation approach is introduced to solve the problem of nonstrict feedback. Third, fuzzy logic systems are utilized to identify the unknown uncertainties, and an adaptive fuzzy output feedback stabilization controller is set up by exploiting the backstepping design principle. At last, by applying the average dwell time method and Lyapunov stability theory, it is proven that all the signals in the closed-loop switched system are bounded, and the system output converges to a small neighborhood of the origin. Two examples are given to further show the effectiveness of the proposed switched control approach. PMID- 26992191 TI - Stacked Convolutional Denoising Auto-Encoders for Feature Representation. AB - Deep networks have achieved excellent performance in learning representation from visual data. However, the supervised deep models like convolutional neural network require large quantities of labeled data, which are very expensive to obtain. To solve this problem, this paper proposes an unsupervised deep network, called the stacked convolutional denoising auto-encoders, which can map images to hierarchical representations without any label information. The network, optimized by layer-wise training, is constructed by stacking layers of denoising auto-encoders in a convolutional way. In each layer, high dimensional feature maps are generated by convolving features of the lower layer with kernels learned by a denoising auto-encoder. The auto-encoder is trained on patches extracted from feature maps in the lower layer to learn robust feature detectors. To better train the large network, a layer-wise whitening technique is introduced into the model. Before each convolutional layer, a whitening layer is embedded to sphere the input data. By layers of mapping, raw images are transformed into high-level feature representations which would boost the performance of the subsequent support vector machine classifier. The proposed algorithm is evaluated by extensive experimentations and demonstrates superior classification performance to state-of-the-art unsupervised networks. PMID- 26992192 TI - Constructing the L2-Graph for Robust Subspace Learning and Subspace Clustering. AB - Under the framework of graph-based learning, the key to robust subspace clustering and subspace learning is to obtain a good similarity graph that eliminates the effects of errors and retains only connections between the data points from the same subspace (i.e., intrasubspace data points). Recent works achieve good performance by modeling errors into their objective functions to remove the errors from the inputs. However, these approaches face the limitations that the structure of errors should be known prior and a complex convex problem must be solved. In this paper, we present a novel method to eliminate the effects of the errors from the projection space (representation) rather than from the input space. We first prove that l1 -, l2 -, linfinity -, and nuclear-norm-based linear projection spaces share the property of intrasubspace projection dominance, i.e., the coefficients over intrasubspace data points are larger than those over intersubspace data points. Based on this property, we introduce a method to construct a sparse similarity graph, called L2-graph. The subspace clustering and subspace learning algorithms are developed upon L2-graph. We conduct comprehensive experiment on subspace learning, image clustering, and motion segmentation and consider several quantitative benchmarks classification/clustering accuracy, normalized mutual information, and running time. Results show that L2-graph outperforms many state-of-the-art methods in our experiments, including L1-graph, low rank representation (LRR), and latent LRR, least square regression, sparse subspace clustering, and locally linear representation. PMID- 26992193 TI - Flocking of Second-Order Multiagent Systems With Connectivity Preservation Based on Algebraic Connectivity Estimation. AB - The problem of flocking of second-order multiagent systems with connectivity preservation is investigated in this paper. First, for estimating the algebraic connectivity as well as the corresponding eigenvector, a new decentralized inverse power iteration scheme is formulated. Then, based on the estimation of the algebraic connectivity, a set of distributed gradient-based flocking control protocols is built with a new class of generalized hybrid potential fields which could guarantee collision avoidance, desired distance stabilization, and the connectivity of the underlying communication network simultaneously. What is important is that the proposed control scheme allows the existing edges to be broken without violation of connectivity constraints, and thus yields more flexibility of motions and reduces the communication cost for the multiagent system. In the end, nontrivial comparative simulations and experimental results are performed to demonstrate the effectiveness of the theoretical results and highlight the advantages of the proposed estimation scheme and control algorithm. PMID- 26992194 TI - GrCS: Granular Computing-Based Crowd Segmentation. AB - Crowd segmentation is important in serving as the basis for a wide range of crowd analysis tasks such as density estimation and behavior understanding. However, due to interocclusions, perspective distortion, clutter background, and random crowd distribution, localizing crowd segments is technically a very challenging task. This paper proposes a novel crowd segmentation framework-based on granular computing (GrCS) to enable the problem of crowd segmentation to be conceptualized at different levels of granularity, and to map problems into computationally tractable subproblems. It shows that by exploiting the correlation among pixel granules, we are able to aggregate structurally similar pixels into meaningful atomic structure granules. This is useful in outlining natural boundaries between crowd and background (i.e., noncrowd) regions. From the structure granules, we infer the crowd and background regions by granular information classification. GrCS is scene-independent and can be applied effectively to crowd scenes with a variety of physical layout and crowdedness. Extensive experiments have been conducted on hundreds of real and synthetic crowd scenes. The results demonstrate that by exploiting the correlation among granules, we can outline the natural boundaries of structurally similar crowd and background regions necessary for crowd segmentation. PMID- 26992195 TI - Novel genetic determinants of adrenal aldosterone regulation. AB - PURPOSE OF REVIEW: Aldosterone regulation in the adrenal plays an important role in blood pressure. The commonest curable cause of hypertension is primary aldosteronism. Recently, mutations in novel genes have been identified to cause primary aldosteronism. Elucidating the mechanism of action of these genetic abnormalities may help understand the cause of primary aldosteronism and the physiological regulation of aldosterone in the zona glomerulosa. RECENT FINDINGS: KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1, and CACNA1H mutations are causal of primary aldosteronism. ARMC5 may cause bilateral lesions resulting in primary aldosteronism.LGR5, DACH1, and neuron-specific proteins are highly expressed in the zona glomerulosa and regulate aldosterone production. SUMMARY: Most mutations causing primary aldosteronism are in genes encoding cation channels or pumps, leading to increased calcium influx. Genotype-phenotype analyses identified two broad subtypes of aldosterone-producing adenomas (APAs), zona fasciculata-like and zona glomerulosa-like, and the likelihood of under-diagnosed zona glomerulosa like APAs because of small size. Zona fasciculata-like APAs are only associated with KCNJ5 mutations, whereas zona glomerulosa-like APAs are associated with mutations in ATPase pumps, CACNA1D, and CTNNB1. The frequency of APAs, and the multiplicity of causal mutations, suggests a pre-existing drive for these mutations. We speculate that these mutations are selected for protecting against tonic inhibition of aldosterone in human zona glomerulosa, which express genes inhibiting aldosterone production. PMID- 26992196 TI - Arsenic Species in Chicken Breast: Temporal Variations of Metabolites, Elimination Kinetics, and Residual Concentrations. AB - BACKGROUND: Chicken meat has the highest per capita consumption among all meat types in North America. The practice of feeding 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox) to chickens lasted for more than 60 years. However, the fate of Rox and arsenic metabolites remaining in chicken are poorly understood. OBJECTIVES: We aimed to determine the elimination of Rox and metabolites from chickens and quantify the remaining arsenic species in chicken meat, providing necessary information for meaningful exposure assessment. METHODS: We have conducted a 35-day feeding experiment involving 1,600 chickens, of which half were control and the other half were fed a Rox-supplemented diet for the first 28 days and then a Rox-free diet for the final 7 days. We quantified the concentrations of individual arsenic species in the breast meat of 229 chickens. RESULTS: Rox, arsenobetaine, arsenite, monomethylarsonic acid, dimethylarsinic acid, and a new arsenic metabolite, were detected in breast meat from chickens fed Rox. The concentrations of arsenic species, except arsenobetaine, were significantly higher in the Rox-fed than in the control chickens. The half-lives of elimination of these arsenic species were 0.4-1 day. Seven days after termination of Rox feeding, the concentrations of arsenite (3.1 MUg/kg), Rox (0.4 MUg/kg), and a new arsenic metabolite (0.8 MUg/kg) were significantly higher in the Rox-fed chickens than in the control. CONCLUSION: Feeding of Rox to chickens increased the concentrations of five arsenic species in breast meat. Although most arsenic species were excreted rapidly when the feeding of Rox stopped, arsenic species remaining in the Rox-fed chickens were higher than the background levels. CITATION: Liu Q, Peng H, Lu X, Zuidhof MJ, Li XF, Le XC. 2016. Arsenic species in chicken breast: temporal variations of metabolites, elimination kinetics, and residual concentrations. Environ Health Perspect 124:1174-1181; http://dx.doi.org/10.1289/ehp.1510530. PMID- 26992197 TI - Controversies in criteria for liver transplantation in hepatocellular carcinoma. AB - PURPOSE OF REVIEW: For patients with hepatic decompensation and hepatocellular carcinoma (HCC) within Milan criteria, liver transplantation provides the best long-term recurrence-free survival. However, there is controversy about the role of liver transplantation in other subgroups, including those with compensated cirrhosis, United Network for Organ Sharing (UNOS) T1 lesions, or HCC exceeding Milan criteria. RECENT FINDINGS: For patients with compensated cirrhosis, surgical resection provides similar recurrence-free survival as liver transplantation and is the most cost-effective approach. Although a 'Wait and not Ablate' approach can facilitate priority listing in most patients with UNOS T1 lesions, nearly 10% will have rapid tumor growth beyond transplant criteria, thereby missing an opportunity for curative therapy. Patients exceeding Milan criteria have higher posttransplant recurrence rates and worse survival than those within Milan criteria, and any potential benefit of liver transplantation to these patients must be weighed against harms to others on the waiting list, particularly in areas with limited donor availability. Although downstaging may help select a subgroup of patients beyond Milan with good tumor biology and better prognosis, limitations of the current literature preclude rigorous evaluation. SUMMARY: Until higher quality data become available that demonstrate transplant benefit in expanded criteria patients, liver transplantation should be reserved for patients within Milan criteria. PMID- 26992198 TI - Multimodal Therapy of Ulcers on the Dorsum of the Hand With Exposed Tendons Caused by Pyoderma Gangrenosum. AB - The authors present the case of a 54-year-old man with ulcers on the dorsal hand and forearm with exposed extensor tendons after he received misdiagnoses at 2 other hospitals, leading to deep soft tissue defects from multiple debridements. Due to the complicated nature of the wound, the ulcers did not heal under the systemic medication. After careful debridement, the defect was primarily closed with a collagen-glycosaminoglycan biodegradable matrix (Integra Matrix Wound Dressing, Integra LifeSciences, Plainsboro, NJ) on the dorsal hand and covered with a mesh graft 14 days later. Necrosis and superinfection over the index finger was treated again with systemic antibiotics and an unmeshed skin graft under a vacuum bandage with a mesh wound contact layer (Mepitel, Molnlycke Health Care, Norcross, GA). The patient was satisfied with the functional and aesthetic outcome 1 month later when wounds were completely healed. The authors conclude that in cases where patients are living with pyoderma gangrenosum, even a challenging and complicated wound can be handled successfully with correct systemic immuno- suppression and appropriate soft tissue coverage. PMID- 26992200 TI - Iron homeostasis after blood transfusion in stable preterm infants - an observational study. AB - AIM: To evaluate the short-term effects of blood transfusion on iron status [hemoglobin, ferritin, soluble transferrin receptor (sTfR), and reticulocyte count], hepcidin, and erythropoietin in stable preterm infants. METHOD: Sixty three preterm infants treated with red blood cell transfusions (RBCTs) were included. Venous blood samples were collected before and within 24 h after each transfusion. RESULTS: Hemoglobin concentration increased after RBCT (7.2+/-1.2 g/dL vs. 13.7+/-2.3 g/dL, P=0.02), as well as ferritin [131 (63-110.4) ng/mL vs. 211 (125.7-299.2) ng/mL, P=0.05); reticulocyte count decreased. sTfR did not change. Hepcidin serum levels increased from 37.5 (21.3-84.7) ng/mL to 72.6 (31.3 126.2) ng/mL, (P=0.04) and erythropoietin decreased (48+/-19 pg/mL vs. 29+/-17 pg/mL, P=0.06) after RBCT. A positive linear correlation was found (R2=0.76, P=0.0001) between hepcidin and ferritin levels of post-minus-pre RBCT. Hepcidin levels increased significantly in preterm infants who received RBCT after 1 month of age compared to those who received RBCT at <1 month (P=0.03). No correlation was found between gestational age, weight appropriate for age, or length of blood storage and hepcidin levels. CONCLUSION: Preterm infants can control iron levels by regulating hepcidin and decreasing erythropoietin. This ability varies with postnatal age. PMID- 26992199 TI - Multifaceted and personalized therapy of advanced prostate cancer. AB - PURPOSE OF REVIEW: A number of molecular and genomic biomarkers that possess the ability to guide treatment or 'actionable targets' are being reported in metastatic prostate cancer. In addition, pathways of resistance to existing therapies and novel agents to overcome them are currently under active investigation. The next wave of investigations is focused on personalized therapy of prostate cancer. The focus of this review article is to provide an update on clinical development in advanced prostate cancer and to highlight the ongoing investigations of biomarker discovery, and ways of overcoming therapeutic resistance. The next generation of clinical trials developing novel targets and compounds promises to be in populations enriched with specific marker expression. RECENT FINDINGS: The breakthrough report, of the ability of the androgen receptor variant 7 mutation, detected in circulating tumor cells, to predict the lack of response to abiraterone or enzalutamide, and the remarkable responses of poly adenosine diphosphate ribose polymerase inhibitors in prostate cancer with DNA repair mutations have elevated hopes of a bright future in the biomarker-driven therapeutic arena. Novel targets such as bromodomain extra terminal-1 and phosphatidylinositol 3-kinase hold promise for the possibility of overcoming resistance. Novel hormone agents are also under active study. SUMMARY: As the clinical application of the multifaceted therapies narrows down to enriched patient populations selected by genomic testing, the therapeutic efficiency will escalate considerably. Novel targets, resistance mechanisms and relevant agents are being avidly tested, and the dream of personalized medicine is emerging into reality. PMID- 26992201 TI - Interstitial cells of Cajal and telocytes in the gut: twins, related or simply neighbor cells? AB - In the interstitium of the connective tissue several types of cells occur. The fibroblasts, responsible for matrix formation, the mast cells, involved in local response to inflammatory stimuli, resident macrophages, plasma cells, lymphocytes, granulocytes and monocytes, all engaged in immunity responses. Recently, another type of interstitial cell, found in all organs so far examined, has been added to the previous ones, the telocytes (TC). In the gut, in addition to the cells listed above, there are also the interstitial cells of Cajal (ICC), a peculiar type of cell exclusively detected in the alimentary tract with multiple functions including pace-maker activity. The possibility that TC and ICC could correspond to a unique cell type, where the former would represent an ICC variant outside the gut, was initially considered, however, further studies have clearly shown that ICC and TC are two distinct types of cells. In the gut, while the features and the roles of the ICC are established, part of the scientific community is still disputing these 'new' interstitial cells to which several names such as fibroblast-like cells (FLCs), interstitial Cajal-like cells or, most recently, PDGFRalpha+ cells have been attributed. This review will detail the main features and roles of the TC and ICC with the aim to establish their relationships and hopefully define the identity of the TC in the gut. PMID- 26992202 TI - Testing differentially expressed genes in dose-response studies and with ordinal phenotypes. AB - When testing for differentially expressed genes between more than two groups, the groups are often defined by dose levels in dose-response experiments or ordinal phenotypes, such as disease stages. We discuss the potential of a new approach that uses the levels' ordering without making any structural assumptions, such as monotonicity, by testing for zero variance components in a mixed models framework. Since the mixed effects model approach borrows strength across doses/levels, the test proposed can also be applied when the number of dose levels/phenotypes is large and/or the number of subjects per group is small. We illustrate the new test in simulation studies and on several publicly available datasets and compare it to alternative testing procedures. All tests considered are implemented in R and are publicly available. The new approach offers a very fast and powerful way to test for differentially expressed genes between ordered groups without making restrictive assumptions with respect to the true relationship between factor levels and response. PMID- 26992203 TI - A graph theoretical approach to data fusion. AB - The rapid development of high throughput experimental techniques has resulted in a growing diversity of genomic datasets being produced and requiring analysis. Therefore, it is increasingly being recognized that we can gain deeper understanding about underlying biology by combining the insights obtained from multiple, diverse datasets. Thus we propose a novel scalable computational approach to unsupervised data fusion. Our technique exploits network representations of the data to identify similarities among the datasets. We may work within the Bayesian formalism, using Bayesian nonparametric approaches to model each dataset; or (for fast, approximate, and massive scale data fusion) can naturally switch to more heuristic modeling techniques. An advantage of the proposed approach is that each dataset can initially be modeled independently (in parallel), before applying a fast post-processing step to perform data integration. This allows us to incorporate new experimental data in an online fashion, without having to rerun all of the analysis. We first demonstrate the applicability of our tool on artificial data, and then on examples from the literature, which include yeast cell cycle, breast cancer and sporadic inclusion body myositis datasets. PMID- 26992205 TI - Increased chemoresistance via Snail-Raf kinase inhibitor protein signaling in colorectal cancer in response to a nicotine derivative. AB - A tobacco-specific component, 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK), is a major risk factor for many cancers. Recent reports have demonstrated that NNK exposure may be associated with tumor progression and chemoresistance in certain cancers. However, the underlying NNK-induced mechanism contributing to the aggressiveness of colorectal cancer (CRC) has not been thoroughly studied. In this study, we used HT29 cells treated with NNK to simulate the long-term exposure of cigarette smoke. A comparative analysis was performed to evaluate cell proliferation, migration, and invasion as well as epithelial-mesenchymal transition (EMT) markers and drug-resistance genes expression, cancer stem cell (CSC) properties, and anti-apoptotic activity. Signaling pathways related to chemoresistance were also investigated. As a result, NNK exposure dose dependently stimulates cell proliferation, enhance abilities of migration and invasion, induce EMT phenomenon, and attenuate apoptosis. Furthermore, NNK exposure also promotes the capabilities of sphere formation, upregulation of Snail, and overexpression of CD133, Nanog, OCT4, and the drug-resistant genes. Knockdown of Snail results in upregulation of Raf kinase inhibitor protein (RKIP), increased apoptosis, reversal of EMT phenomenon, and reducation of expression of CSC markers, all of which contribute to a decrease of chemoresistance. Our study demonstrates a number of related mechanisms that mediate the effect of NNK exposure on increasing CRC therapeutic resistance via the Snail signaling pathway. Targeting Snail may provide a feasible strategy for the treatment of CRC. PMID- 26992204 TI - Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL- induced apoptosis. AB - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL is regarded as one of the most promising anticancer agents, because it can destruct cancer cells without showing any toxicity to normal cells. Metformin is an anti-diabetic drug with anticancer activity by inhibiting tumor cell proliferation. In this study, we demonstrated that metformin could induce TRAIL-mediated apoptotic cell death in TRAIL-resistant human lung adenocarcinoma A549 cells. Pretreatment of metformindownregulation of c-FLIP and markedly enhanced TRAIL-induced tumor cell death by dose-dependent manner. Treatment with metformin resulted in slight increase in the accumulation of microtubule-associated protein light chain LC3-II and significantly decreased the p62 protein levels by dose-dependent manner indicated that metformin induced autophagy flux activation in the lung cancer cells. Inhibition of autophagy flux using a specific inhibitor and genetically modified ATG5 siRNA blocked the metformin-mediated enhancing effect of TRAIL. These data demonstrated that downregulation of c-FLIP by metformin enhanced TRAIL-induced tumor cell death via activating autophagy flux in TRAIL-resistant lung cancer cells and also suggest that metformin may be a successful combination therapeutic strategy with TRAIL in TRAIL-resistant cancer cells including lung adenocarcinoma cells. PMID- 26992206 TI - Radiation dose escalation by simultaneous modulated accelerated radiotherapy combined with chemotherapy for esophageal cancer: a phase II study. AB - The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common >= grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed >= Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities. PMID- 26992207 TI - High expression of C-C chemokine receptor 2 associates with poor overall survival in gastric cancer patients after surgical resection. AB - BACKGROUND: Being a critical chemokine receptor in chemoattracting myeloid cells into tumor tissues, C-C chemokine receptor 2 (CCR2) has been detected in many malignant tumors. This study aims to evaluate the prognostic value of CCR2 expression in patients with gastric cancer after surgery. RESULTS: CCR2 expression was detected in the accessory cells around gastric cancer cells in a diffused manner. CCR2 high expression was correlated with tumor invasion depth (P=0.006 and P=0.004, respectively), lymph node metastasis (P=0.038 and P=0.011, respectively) and TNM stage (P=0.003 and P=0.001, respectively) in the two independent sets. Multivariate Cox regression analysis identifies CCR2 high expression was an independent poor prognostic factor for OS of patients with gastric cancer in the two sets (P=0.013 and P=0.006, respectively). Integration of CCR2 expression and TNM stage could provide additional prognostic value for OS than TNM stage alone in the two sets (P=0.038 and P=0.002, respectively). METHODS: Two independent sets comprising a total of 474 patients who received standard gastrectomy were enrolled in the study. The expression level of CCR2 was detected by immunohistochemistry. The correlations between CCR2 expression and clinicopathological factors were explored, and the prognostic significance for overall survival (OS) was determined by Kaplan-Meier analysis. CONCLUSIONS: CCR2 high expression in the tumor microenvironment is a novel independent unfavorable prognostic factor for patients with gastric cancer. Combination of CCR2 expression and TNM stage could provide a better prognostic model for OS of gastric cancer patients. PMID- 26992208 TI - Distinct effects of SIRT1 in cancer and stromal cells on tumor promotion. AB - The lysyl deacetylase SIRT1 acts as a metabolic sensor in adjusting metabolic imbalance. To explore the role of SIRT1 in tumor-stroma interplay, we designed an in vivo tumor model using SIRT1-transgenic mice. B16F10 mouse melanoma grew more quickly in SIRT1-transgenic mice than in wild-type mice, whereas SIRT1 overexpressing one grew slowly in both mice. Of human tumors, SIRT1 expression in stromal fibroblasts was found to correlate with poor prognosis in ovarian cancer. B16F10 and human ovarian cancer (SKOV3 and SNU840) cells were more proliferative in co-culture with SIRT1-overexpressiong fibroblasts. In contrast, SIRT1 within cancer cells has a negative effect on cell proliferation. In conditioned media from SIRT1-overexpressing fibroblasts, matrix metalloproteinase-3 (MMP3) was identified in cytokine arrays to be secreted from fibroblasts SIRT1-dependently. Fibroblast-derived MMP3 stimulated cancer cell proliferation, and such a role of MMP3 was also demonstrated in cancer/fibroblast co-grafts. In conclusion, SIRT1 plays differential roles in cancer and stromal cells. SIRT1 in stromal cells promotes cancer growth by producing MMP3, whereas SIRT1 in cancer cells inhibits growth via an intracellular event. The present study provides a basis for setting new anticancer strategies targeting SIRT1. PMID- 26992210 TI - Impact of the number of resected lymph nodes on survival after preoperative radiotherapy for esophageal cancer. AB - To assess the impact of the number of resected lymph nodes (RLNs) for survival in esophageal cancer (EC) patients treated with preoperative radiotherapy and cancer directed surgery. The Surveillance Epidemiology and End Results (SEER) database was queried to identify EC patients treated from 1988 to 2012 who had complete data on the number of positive lymph nodes and number of RLNs. Kaplan-Meier survival analysis and Cox regression proportional hazard methods were used to determine factors that significantly impact cause-specific survival (CSS) and overall survival (OS). There were a total of 3,159 patients who received preoperative radiotherapy and cancer-directed surgery. The median number of RLNs was 10 in both patients who received and did not receive preoperative radiotherapy (P = 0.332). Cox regression univariate and multivariate analysis showed that RLN count was a significant prognostic factor for CSS and OS. Patients with 11-71 RLNs had better CSS (hazard ratio [HR] = 0.694, 95% confidence interval [CI]: 0.603-0.799, P < 0.001) and OS (HR = 0.724, 95% CI: 0.636-0.824, P < 0.001) than patients with 1-10 RLNs. The 5-year CSS rates were 39.1% and 44.8% in patients with 1-10 RLNs and 11-71 RLNs, respectively (P < 0.001). The 5-year OS rates were 33.7% and 39.9% in patients with 1-10 RLNs and 11-71 RLNs, respectively (P < 0.001). A higher number of RLNs was associated with better survival by tumor stage and nodal stage (all P < 0.05). RLN count is an independent prognostic factor in EC patients who undergo preoperative radiotherapy and cancer-directed surgery. PMID- 26992209 TI - Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers. AB - BACKGROUND: EGFR, KRAS, and ALK alterations are major genetic changes found in non-small cell lung cancers (NSCLCs). Testing advanced lung adenocarcinoma tumors for these three genes is now standard care. The purpose of this study was to investigate the clinicopathologic expression pattern of these three genes in East Asian NSCLC patients. PATIENTS AND METHODS: We conducted a retrospective study of all patients tested for mutations of these three genes at a single institute in Korea between 2006 and 2014. Study data were extracted from electronic medical records. Univariate and multivariate logistic regression analyses were used to measure associations between clinicopathologic features and alterations of EGFR, KRAS, and ALK. RESULTS: We detected 12 EGFR-mutated tumors with additional mutations in KRAS (N=6, 0.1%) or ALK (N=6, 0.1%). General clinicopathologic characteristics of tumors with EGFR, KRAS, or ALK mutations were similar to previous reports. Patients having EGFR L858R point mutations were older than patients having EGFR exon 19 deletions. EGFR G719X point mutations were more common in men and smokers than exon 19 deletions or L858R point mutations. Tumors having KRAS G12C mutations were less often of mucinous type than those with G12D or G12V, mutations. CONCLUSIONS: This is the largest three gene molecular epidemiology study in East Asian NSCLC patients. Each genetic alteration was associated with distinct clinicopathologic characteristics. Furthermore, different age and sex are associated with different subtypes of EGFR and KRAS mutations. PMID- 26992211 TI - Armored long non-coding RNA MEG3 targeting EGFR based on recombinant MS2 bacteriophage virus-like particles against hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide. However, the treatment of patients with HCC is particularly challenging. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a potential suppressor of several types of tumors, but the delivery of long RNA remains problematic, limiting its applications. In the present study, we designed a novel delivery system based on MS2 virus-like particles (VLPs) crosslinked with GE11 polypeptide. This vector was found to be fast, effective and safe for the targeted delivery of lncRNA MEG3 RNA to the epidermal growth factor receptor (EGFR)-positive HCC cell lines without the activation of EGFR downstream pathways, and significantly attenuated both in vitro and in vivo tumor cell growth. Our study also revealed that the targeted delivery was mainly dependent on clathrin-mediated endocytosis and MEG3 RNA suppresses tumor growth mainly via increasing the expression of p53 and its downstream gene GDF15, but decreasing the expression of MDM2. Thus, this vector is promising as a novel delivery system and may facilitate a new approach to lncRNA based cancer therapy. PMID- 26992213 TI - Predictive value of angiogenesis-related gene profiling in patients with HER2 negative metastatic breast cancer treated with bevacizumab and weekly paclitaxel. AB - Bevacizumab plus weekly paclitaxel improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC), but its use has been questioned due to the absence of a predictive biomarker, lack of benefit in overall survival (OS) and increased toxicity. We examined the baseline tumor angiogenic-related gene expression of 60 patients with mBC with the aim of finding a signature that predicts benefit from this drug.Multivariate analysis by Lasso-penalized Cox regression generated two predictive models: one, named G-model, including 11 genes, and the other one, named GC-model, including 13 genes plus 5 clinical covariates. Both models identified patients with improved PFS (HR (Hazard Ratio) 2.57 and 4.04, respectively) and OS (HR 3.29 and 3.43, respectively). The G-model distinguished low and high risk patients in the first 6 months, whereas the GC model maintained significance over time. PMID- 26992212 TI - Tumor necrosis factor receptor 2-signaling in CD133-expressing cells in renal clear cell carcinoma. AB - Compared to normal kidney, renal clear cell carcinomas (ccRCC) contain increased numbers of interstitial, non-hematopoietic CD133+cells that express stem cell markers and exhibit low rates of proliferation. These cells fail to form tumors upon transplantation but support tumor formation by differentiated malignant cells. We hypothesized that killing of ccRCC CD133+ (RCCCD133+) cells by cytotoxic agents might be enhanced by inducing them to divide. Since tumor necrosis factor-alpha (TNF), signalling through TNFR2, induces proliferation of malignant renal tubular epithelial cells, we investigated whether TNFR2 might similarly affect RCCCD133+cells. We compared treating organ cultures of ccRCC vs adjacent nontumour kidney (NK) and RCCCD133+vs NK CD133+ (NKCD133+) cell cultures with wild-type TNF (wtTNF) or TNF muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF). In organ cultures, R2TNF increased expression of TNFR2 and promoted cell cycle entry of both RCCCD133+ and NKCD133+ but effects were greater in RCCCD133+. In contrast, R1TNF increased TNFR1 expression and promoted cell death. Importantly, cyclophosphamide triggered much more cell death in RCCCD133+ and NKCD133+cells pre-treated with R2TNF as compared to untreated controls. We conclude that selective engagement of TNFR2 by TNF can drives RCCCD133+ proliferation and thereby increase sensitivity to cell cycle-dependent cytotoxicity. PMID- 26992214 TI - Clinical predictive factors of pathologic complete response in locally advanced rectal cancer. AB - BACKGROUND: Predictive factors of pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) are still not identified. The purpose of this study was to define them. MATERIALS AND METHODS: Data from consecutive LARC patients treated between January 2008 and June 2014 at our Institution were included in the analysis. All patients were treated with a long course of nCRT. Demographics, initial diagnosis and tumor extension details, as well as treatment modalities characteristics were included in the univariate and logistic regression analysis. RESULTS: In total 99 patients received nCRT, of whom 23 patients (23.2%) achieved pCR. Patients with and without pCR were similar in term of age, sex, comobidities, BMI and tumor characteristics. Multivariate logistic regression indicated that pre-treatment tumor size <= 5 cm was a significant predictor for pCR (p = 0.035), whereas clinical N stage only showed a positive trend (p = 0.084). CONCLUSIONS: Tumor size at diagnosis could be used to predict pCR, and thus to individualize therapy in LARC patients management. Validation in other studies is needed. PMID- 26992215 TI - Deinococcus radiodurans pprI expression enhances the radioresistance of eukaryotes. AB - PprI accelerates radiation-induced DNA damage repair via regulating the expression of DNA repair genes and enhances antioxidative enzyme activity in Deinococcus radiodurans after radiation. The main aim of our study was to determine whether the expression of pprI gene could fulfil its DNA repair function in eukaryotes and enhance the radioresistance of eukaryotic organism or not. In this study, we constructed pEGFP-c1-pprI eukaryotic expression vector and established a human lung epithelial cell line BEAS-2B with stable integration of pprI gene. We found that pprIexpression enhanced radioresistance of BEAS-2B cells, decreased gamma-H2AX foci formation and apoptosis in irradiated BEAS-2B cells and alleviated radiation induced G2/M arrest of BEAS-2B cells. Moreover, we transferred pEGFP-c1-pprI vector into muscle of BALB/c mice by in vivo electroporation and studied the protective effect of prokaryotic pprI gene in irradiated mice. We found that pprI expression alleviated acute radiation induced hematopoietic system, lung, small intestine and testis damage and increased survival rate of irradiated mice via regulating Rad51 expression in different organs. These findings suggest that prokaryotic pprI gene expression in mammalian cells could enhance radioresistance in vitro and in vivo. PMID- 26992216 TI - The Wilms Tumor-1 (WT1) rs16754 polymorphism is a prognostic factor in acute myeloid leukemia (AML): a meta-analysis. AB - Although a number of studies suggested that WT1 rs16754 polymorphism might be related to decreased relapse free survival (RFS) and overall survival (OS). The results remain controversial. Published reports were searched in PubMed, EMBASE, and Google Scholar. Twelve publications with 3903 patients had met the inclusion criteria and were subjected to further examination. We found WT1 rs16754 polymorphism was significantly associated with OS in AML (OR = 0.62; 95% CI 0.52 0.75; p < 0.00001; I2 = 47%). WT1 rs16754 polymorphism was also significantly associated with RFS in AML (OR = 0.69; 95% CI 0.57 - 0.83; p < 0.001; I2 = 46%). In the subgroup analyses of age, race, and subtype of AML, WT1 rs16754 polymorphism was a independent favorable-risk marker. In conclusion, WT1 rs16754 polymorphism is associated with better survival of AML. It could be used as a cost-effective prognostic biomarker for AML. PMID- 26992217 TI - In silico analyses identify gene-sets, associated with clinical outcome in ovarian cancer: role of mitotic kinases. AB - INTRODUCTION: Accurate assessment of prognosis in early stage ovarian cancer is challenging resulting in suboptimal selection of patients for adjuvant therapy. The identification of predictive markers for cytotoxic chemotherapy is therefore highly desirable. Protein kinases are important components in oncogenic transformation and those relating to cell cycle and mitosis control may allow for identification of high-risk early stage ovarian tumors. METHODS: Genes with differential expression in ovarian surface epithelia (OSE) and ovarian cancer epithelial cells (CEPIs) were identified from public datasets and analyzed with dChip software. Progression-free (PFS) and overall survival (OS) associated with these genes in stage I/II and late stage ovarian cancer was explored using the Kaplan Meier Plotter online tool. RESULTS: Of 2925 transcripts associated with modified expression in CEPIs compared to OSE, 66 genes coded for upregulated protein kinases. Expression of 9 of these genes (CDC28, CHK1, NIMA, Aurora kinase A, Aurora kinase B, BUB1, BUB1betaB, CDKN2A and TTK) was associated with worse PFS (HR:3.40, log rank p<0.001). The combined analyses of CHK1, CDKN2A, AURKA, AURKB, TTK and NEK2 showed the highest magnitude of association with PFS (HR:4.62, log rank p<0.001). Expression of AURKB predicted detrimental OS in stage I/II ovarian cancer better than all other combinations Conclusion: Genes linked to cell cycle control are associated with worse outcome in early stage ovarian cancer. Incorporation of these biomarkers in clinical studies may help in the identification of patients at high risk of relapse for whom optimizing adjuvant therapeutic strategies is needed. PMID- 26992218 TI - Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Accumulating studies have demonstrated that aberrant expression of several lncRNAs was found to be involved in the hepatocarcinogenesis. In this study, a lncRNA Ftx was chosen to investigate its effects on HCC cells, and clarify the possible mechanism. We demonstrated that the lncRNA Ftx and Ftx derived miR-545 were up-regulated in both HCC tissues and cells. MiR-545 was positively correlated with lncRNA Ftx expression. Notably, clinical association analysis revealed that the high expression of lncRNA Ftx and miR-545 was associated with poor prognostic features, and conferred a reduced 5-year overall survival (OS) and disease-free survival (DFS) of HCC patients. We found that miR 545 was a pivotal mediator in Ftx-induced promotion of HCC cell growth. Subsequently, we identified RIG-I as a direct target of miR-545. The expression of RIG-I was downregulated in HCC tissues and was inversely correlated with miR 545 expression. Our data revealed that ectopic expression of RIG-I abrogated the effects of lncRNA Ftx or miR-545 on HCC cells. LncRNA Ftx/miR-545-mediated downregulation of RIG-I led to increased Akt phosphorylation in vitro and in vivo. Inhibition of Akt phosphorylation abolished the effects of lncRNA Ftx/miR 545 on HCC cells. In conclusion, our study demonstrates that the novel pathway lncRNA Ftx/miR-545/RIG-I promotes HCC development by activating PI3K/Akt signaling, and it may serve as a novel prognostic biomarker and therapeutic target for HCC. PMID- 26992219 TI - DEPTOR promotes survival of cervical squamous cell carcinoma cells and its silencing induces apoptosis through downregulating PI3K/AKT and by up-regulating p38 MAP kinase. AB - DEPTOR is an endogenous inhibitor of mTOR complexes, de-regulated in cancers. The present study reveals a vital role for DEPTOR in survival of cervical squamous cell carcinoma (SCC). DEPTOR was found to be overexpressed in both cervical SCC cells and tissues and it's silencing in cervical SCC cells induced apoptosis, mainly by up-regulation of p38 MAPK and by inhibiting PI3K/AKT pathway via a feed back inhibition from mTORC1-S6K. DEPTOR silencing resulted in reduced expression of the nitric oxide synthases iNOS and eNOS, as well as increased activation of ERK1/2 and p38 MAP kinases. Activation of AKT signaling by overexpression of constitutively active-AKT (CA-AKT) failed to overcome the apoptosis caused by DEPTOR silencing. Similarly pharmacological inhibition of ERK also failed to control apoptosis. However pharmacological inhibition of p38 MAPK rescued the cells from apoptosis, indicating the major role of p38 MAPK in cell death induced by DEPTOR silencing. DEPTOR was also found to regulate ERK1/2 in an AKT dependent manner. DEPTOR knockdown induced cell death in SiHa cells overexpressing the anti apoptotic Bcl-2 and Bcl-xL, indicating strong survival role of DEPTOR in these cells. DEPTOR overexpression activated PI3K/AKT by relieving the negative feed back inhibition from mTORC1-S6K. DEPTOR regulation was also observed to be independent of HPV E6/E7 oncoproteins, but it might be a molecular co-factor contributing to cervical carcinogenesis. In summary, DEPTOR is found to promote survival of cervical SCC cells and its reduction induced apoptosis via differential effects on PI3K/AKT and p38 MAPK and can be a potential target in cervical SCC. PMID- 26992220 TI - Genomic profiling of lung adenocarcinoma patients reveals therapeutic targets and confers clinical benefit when standard molecular testing is negative. AB - BACKGROUND: Identification of clinically relevant oncogenic drivers in advanced cancer is critical in selecting appropriate targeted therapy. Using next generation sequencing (NGS)-based clinical cancer gene assay, we performed comprehensive genomic profiling (CGP) of advanced cases of lung adenocarcinoma. METHODS: Formalin-fixed paraffin-embedded tumors from 51 lung adenocarcinoma patients whose tumors previously tested negative for EGFR/KRAS/ALK by conventional methods were collected, and CGP was performed via hybridization capture of 4,557 exons from 287 cancer-related genes and 47 introns from 19 genes frequently rearranged in cancer. RESULTS: Genomic profiles of all 51 cases were obtained, with a median coverage of 564x and a total of 190 individual genomic alterations (GAs). GAs per specimen was a mean of 3.7 (range 0-10).Cancer genomes are characterized by 50% (80/190) non-synonymous base substitutions, 15% (29/190) insertions or deletion, and 3% (5/190) splice site mutation. TP53 mutation was the most common GAs (15%, n=29/190), followed by CDKN2A homozygous loss (5%, n=10/190), KRAS mutation (4%, n=8/190), EGFR mutation (4%, n=8/190) and MDM2 amplification (2%, n=5/190). As per NCCN guidelines, targetable GAs were identified in 16 patients (31%) (BRAF mutation [n=1], EGFR mutation [n=8], ERBB2 mutation [n=4], MET amplification [n=1], KIF5B-RET rearrangement [n=2], CCDC6-RET rearrangement [n=1], CD74-ROS1 rearrangement [n=1], EZR-ROS1 rearrangement [n=5], and SLC34A2-ROS1 rearrangement [n=1]). CONCLUSION: Fifty eight percent of patients wild type by standard testing for EGFR/KRAS/ALK have GAs identifiable by CGP that suggest benefit from target therapy. CGP used when standard molecular testing for NSCLC is negative can reveal additional avenues of benefit from targeted therapy. PMID- 26992221 TI - Hepatitis B virus PreS2-mutant large surface antigen activates store-operated calcium entry and promotes chromosome instability. AB - Hepatitis B virus (HBV) is a driver of hepatocellular carcinoma, and two viral products, X and large surface antigen (LHBS), are viral oncoproteins. During chronic viral infection, immune-escape mutants on the preS2 region of LHBS (preS2 LHBS) are gain-of-function mutations that are linked to preneoplastic ground glass hepatocytes (GGHs) and early disease onset of hepatocellular carcinoma. Here, we show that preS2-LHBS provoked calcium release from the endoplasmic reticulum (ER) and triggered stored-operated calcium entry (SOCE). The activation of SOCE increased ER and plasma membrane (PM) connections, which was linked by ER resident stromal interaction molecule-1 (STIM1) protein and PM-resident calcium release- activated calcium modulator 1 (Orai1). Persistent activation of SOCE induced centrosome overduplication, aberrant multipolar division, chromosome aneuploidy, anchorage-independent growth, and xenograft tumorigenesis in hepatocytes expressing preS2- LHBS. Chemical inhibitions of SOCE machinery and silencing of STIM1 significantly reduced centrosome numbers, multipolar division, and xenograft tumorigenesis induced by preS2-LHBS. These results provide the first mechanistic link between calcium homeostasis and chromosome instability in hepatocytes carrying preS2-LHBS. Therefore, persistent activation of SOCE represents a novel pathological mechanism in HBV-mediated hepatocarcinogenesis. PMID- 26992222 TI - Role of isoenzyme M2 of pyruvate kinase in urothelial tumorigenesis. AB - The conversion of precancerous lesions to full-fledged cancers requires the affected cells to surpass certain rate-limiting steps. We recently showed that activation of HRAS proto-oncogene in urothelial cells of transgenic mice causes simple urothelial hyperplasia (SUH) which is persistent and whose transition to low-grade papillary urothelial carcinoma (UC) must undergo nodular urothelial hyperplasia (NUH). We hypothesized that NUH, which has acquired fibrovascular cores, plays critical roles in mesenchymal-to-epithelial signaling, breaching the barriers of urothelial tumor initiation. Using proteomics involving two dimensional gel electrophoresis, immunoblotting with pan-phosphotyrosine antibody and MALDI-mass spectrometry, we identified isoform 2 of pyruvate kinase (PKM2) as the major tyrosine-phosphorylated protein switched on during NUH. We extended this finding using specimens from transgenic mice, human UC and UC cell lines, establishing that PKM2, but not its spliced variant PKM1, was over-expressed in low-grade and, more prominently, high-grade UC. In muscle-invasive UC, PKM2 was co-localized with cytokeratins 5 and 14, UC progenitor markers. Specific inhibition of PKM2 by siRNA or shRNA suppressed UC cell proliferation via increased apoptosis, autophagy and unfolded protein response. These results strongly suggest that PKM2 plays an important role in the genesis of low-grade non-invasive and high-grade invasive urothelial carcinomas. PMID- 26992223 TI - MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/beta-catenin signaling in breast cancer. AB - Constitutive activation of the Wnt/beta-catenin pathway promotes malignant proliferation and it is inversely correlated with the prognosis of patients with breast cancer. However, mutations in key regulators, such as APC, Axin and beta catenin, contribute to aberrant activation of the Wnt/beta-catenin signaling pathway in various cancers, but rarely found in breast cancer, suggesting that other mechanisms might be involved in the activation of Wnt/beta-catenin signaling in breast cancer. In the present study, we found that miR-1229 expression was markedly upregulated in breast cancer and associated with poor survival. Overexpressing miR-1229 promoted while inhibiting miR-1229 reduced, proliferation of breast cancer cell proliferation in vitro and tumor growth in vivo. Furthermore, we found that overexpression of miR-1229 activated the Wnt/beta-catenin signaling pathway in breast cancer by directly targeting the multiple important negative regulators of Wnt/beta-catenin signaling, including adenomatous polyposis coli (APC), glycogen synthase kinase-3beta (GSK-3beta), and inhibitor of beta-catenin and T cell factor (ICAT). Taken together, our results suggest that miR-1229 plays an important role in promotion breast cancer progression and may represent a novel therapeutic target in breast cancer. PMID- 26992224 TI - Upregulation of E2F8 promotes cell proliferation and tumorigenicity in breast cancer by modulating G1/S phase transition. AB - E2F transcription factors are involved in cell cycle regulation and synthesis of DNA in mammalian cells, and simultaneously play important roles in the development and progression of cancer when dysregulated. E2F8, a novel identified E2F family member, was found to be associated with the progression of several human cancers; however, the biological role and clinical significance of E2F8 in breast cancer remain to be further elucidated. Herein, we report that E2F8 is robustly elevated in breast cancer cell lines and clinical breast cancer tissue samples, respectively. The high expression level of E2F8 significantly correlates with clinical progression (P = 0.001), poor patient survival (P < 0.001) and a high Ki67 staining index (P = 0.008) in 187 human breast cancer specimens. Furthermore, we find that overexpressing E2F8 promotes, whereas silencing E2F8 suppresses, the proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo. We further demonstrate that E2F8 transcriptionally upregulates CCNE1 and CCNE2 via directly interacting with their respective gene promoter, which accelerates the transition of G1 to S phase of breast cancer cells. Taken together, these findings uncover a novel biologic role and regulatory mechanism of E2F8 responsible for the progression of breast cancer, indicating E2F8 may represent a novel prognostic biomarker and therapeutic target against breast cancer. PMID- 26992225 TI - Non-invasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles. AB - In many cancer types, the expression and function of ~22 nucleotide-long microRNAs (miRNA) is deregulated. Mature miRNAs can be stably detected in extracellular vesicles (EVs) in biofluids, therefore they are considered to have great potential as biomarkers. In the present study, we investigated whether miRNAs have a distinct expression pattern in urine-EVs of prostate cancer (PCa) patients compared to control males. By next generation sequencing, we determined the miRNA expression in a discovery cohort of 4 control men and 9 PCa patients. miRNAs were validated by using a stemloop RT-PCR in an independent cohort of 74 patients (26 control and 48 PCa-patients). Whereas standard mapping protocols identified > 10 PCa associated miRNAs in urinary EVs, miR-21, miR-375 and miR-204 failed to robustly discriminate for disease in a validation study with RT-PCR detection of mature miRNA sequences. In contrast, we observed that miRNA isoforms (isomiRs) with 3' end modifications were highly discriminatory between samples from control men and PCa patients. Highly differentially expressed isomiRs of miR 21, miR-204 and miR-375 were subsequently validated in an independent group of 74 patients. Receiver-operating characteristic analysis was performed to evaluate the diagnostic performance of three isomiRs, resulting in a 72.9% sensitivity with a high (88%) specificity and an area under the curve (AUC) of 0.866. In comparison, prostate specific antigen had an AUC of 0.707 and measuring the mature form of these miRNAs yielded a lower 70.8% sensitivity and 72% specificity (AUC 0.766). We propose that isomiRs may carry discriminatory information which is useful to generate stronger biomarkers. PMID- 26992226 TI - Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use. AB - Frequent genetic alterations discovered in FGFRs and evidence implicating some as drivers in diverse tumors has been accompanied by rapid progress in targeting FGFRs for anticancer treatments. Wider assessment of the impact of genetic changes on the activation state and drug responses is needed to better link the genomic data and treatment options. We here apply a direct comparative and comprehensive analysis of FGFR3 kinase domain variants representing the diversity of point-mutations reported in this domain. We reinforce the importance of N540K and K650E and establish that not all highly activating mutations (for example R669G) occur at high-frequency and conversely, that some "hotspots" may not be linked to activation. Further structural characterization consolidates a mechanistic view of FGFR kinase activation and extends insights into drug binding. Importantly, using several inhibitors of particular clinical interest (AZD4547, BGJ-398, TKI258, JNJ42756493 and AP24534), we find that some activating mutations (including different replacements of the same residue) result in distinct changes in their efficacy. Considering that there is no approved inhibitor for anticancer treatments based on FGFR-targeting, this information will be immediately translatable to ongoing clinical trials. PMID- 26992227 TI - cRGD inhibits vasculogenic mimicry formation by down-regulating uPA expression and reducing EMT in ovarian cancer. AB - Vasculogenic minicry (VM), an alternative blood supply modality except to endothelial cells-mediated vascular network, is a potential therapeutic target for ovarian cancer due to VM correlated with poor prognosis in ovarian cancer patients. Accelerated extracellular matrix (ECM) degradation is prerequisite for VM formation induced by epithelial-mesenchymal transition (EMT). Previous reports demonstrate uPA has ability to degrade ECM thereby promoting tumor angiogenesis. Also, exogenous cRGD sequence enables to modulate uPA expression, attenuate EMT and suppress endothelial-lined channels. Till now, the correlation of uPA and VM formation and the effect of exogenous cRGD on VM formation remain unknown. Herein, we validate uPA expression is positively correlated with VM formation in ovarian cancer tissues (90 cases) and ovarian cancer cells (SKOV-3, OVCAR-3 and A2780 cells). In particular, silencing uPA experiments show that down-regulated uPA causes notable decrease for the complete channels formed by SKOV-3 and OVCAR 3 cells. Mechanism study discloses uPA promotes VM formation by regulating AKT/mTOR/MMP-2/Laminin5gamma2 signal pathway. The result demonstrates uPA may serve as therapeutic target of VM for ovarian cancer. Also, it is found exogenous cRGD enables to inhibit VM formation in ovarian cancer via not only down regulating uPA expression but also reducing EMT. Exogenous cRGD may be a promising angiogenic inhibitor for ovarian cancer therapy due to its inhibiting effect on VM formation as well as endothelial cells-mediated vascular network. PMID- 26992228 TI - Divergent branches of mitochondrial signaling regulate specific genes and the viability of specialized cell types of differentiated yeast colonies. AB - Mitochondrial retrograde signaling mediates communication from altered mitochondria to the nucleus and is involved in many normal and pathophysiological changes, including cell metabolic reprogramming linked to cancer development and progression in mammals. The major mitochondrial retrograde pathway described in yeast includes three activators, Rtg1p, Rtg2p and Rtg3p, and repressors, Mks1p and Bmh1p/Bmh2p. Using differentiated yeast colonies, we show that Mks1p-Rtg pathway regulation is complex and includes three branches that divergently regulate the properties and fate of three specifically localized cell subpopulations via signals from differently altered mitochondria. The newly identified RTG pathway-regulated genes ATO1/ATO2 are expressed in colonial upper (U) cells, the cells with active TORC1 that metabolically resemble tumor cells, while CIT2 is a typical target induced in one subpopulation of starving lower (L) cells. The viability of the second L cell subpopulation is strictly dependent on RTG signaling. Additional co-activators of Rtg1p-Rtg3p specific to particular gene targets of each branch are required to regulate cell differentiation. PMID- 26992229 TI - Downregulation of the stress-induced ligand ULBP1 following SV40 infection confers viral evasion from NK cell cytotoxicity. AB - Polyomaviruses are a diverse family of viruses which are prevalent in the human population. However, the interactions of these viruses with the immune system are not well characterized. We have previously shown that two human polyomaviruses, JC and BK, use an identical microRNA to evade immune attack by Natural Killer (NK) cells. We showed that this viral microRNA suppresses ULBP3 expression, a stress induced ligand for the killer receptor NKG2D. Here we show that Simian Virus 40 (SV40) also evades NK cell attack through the down regulation of another stress-induced ligand of NKG2D, ULBP1. These findings indicate that NK cells play an essential role in fighting polyomavirus infections and further emphasize the importance of various members of the ULBP family in controlling polyomavirus infection. PMID- 26992230 TI - Reduced serpinB9-mediated caspase-1 inhibition can contribute to autoinflammatory disease. AB - Patients who suffer from autoinflammatory disease (AID) exhibit seemingly uncontrolled release of interleukin (IL)-1beta. The presence of this inflammatory cytokine triggers immune activation in absence of pathogens and foreign material. The mechanisms that contribute to 'sterile inflammation' episodes in AID patients are not fully understood, although for some AIDs underlying genetic causes have been identified. We show that the serine protease inhibitor B9 (serpinB9) regulates IL-1beta release in human monocytes. SerpinB9 function is more commonly known for its role in control of granzyme B. SerpinB9 however also serves to restrain IL-1beta maturation through caspase-1 inhibition. We here describe an autoinflammatory disease-associated serpinB9 (c.985G>T, A329S) variant, which we discovered in a patient with unknown AID. Using patient cells and serpinB9 overexpressing monocytic cells, we show the A329S variant of serpinB9 exhibits unobstructed granzyme B inhibition, but compromised caspase-1 inhibition. SerpinB9 gene variants might contribute to AID development. PMID- 26992231 TI - RNA methyltransferase NSUN2 promotes stress-induced HUVEC senescence. AB - The tRNA methyltransferase NSUN2 delays replicative senescence by regulating the translation of CDK1 and CDKN1B mRNAs. However, whether NSUN2 influences premature cellular senescence remains untested. Here we show that NSUN2 methylates SHC mRNA in vitro and in cells, thereby enhancing the translation of the three SHC proteins, p66SHC, p52SHC, and p46SHC. Our results further show that the elevation of SHC expression by NSUN2-mediated mRNA methylation increased the levels of ROS, activated p38MAPK, thereby accelerating oxidative stress- and high-glucose induced senescence of human vascular endothelial cells (HUVEC). Our findings highlight the critical impact of NSUN2-mediated mRNA methylation in promoting premature senescence. PMID- 26992232 TI - Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior. AB - Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The dopamine (DA) system is known to be vulnerable to the effects of aging, which regulate behavioral functions such as locomotor activity, body weight, and reward and cognition. In particular, age-related DA D2 receptor (D2R) changes have been of particular interest given its relationship with addiction and other rewarding behavioral properties. Male and female wild-type (Drd2 +/+), heterozygous (Drd2 +/-) and knockout (Drd2 -/-) mice were reared post-weaning in either an enriched environment (EE) or a deprived environment (DE). Over the course of their lifespan, body weight and locomotor activity was assessed. While an EE was generally found to be correlated with longer lifespan, these increases were only found in mice with normal or decreased expression of the D2 gene. Drd2 +/+ EE mice lived nearly 16% longer than their DE counterparts. Drd2 +/+ and Drd2 +/- EE mice lived 22% and 21% longer than Drd2 -/- EE mice, respectively. Moreover, both body weight and locomotor activity were moderated by environmental factors. In addition, EE mice show greater behavioral variability between genotypes compared to DE mice with respect to body weight and locomotor activity. PMID- 26992234 TI - Longterm effects of palliative local treatment of incurable metastatic lesions in colorectal cancer patients. AB - We assessed the value of palliative local treatment of incurable metastatic lesions in colorectal cancer patients. Consecutive patients with metastatic colorectal cancer treated between 2003 and 2014 were retrospectively reviewed. Propensity score matching was used to create comparable palliative local treatment and chemotherapy alone groups (n = 272 in each group). The primary endpoint was overall survival, which was calculated using Kaplan-Meier survival analyses. Factors possibly influencing survival were evaluated by univariate and subsequently by multivariate analyses. Palliative local treatment prolonged survival as compared with chemotherapy alone (38.73 vs. 19.8 months, p < 0.01). Univariate and subsequent multivariate analyses showed that primary stage IV at initial diagnosis; high CA199 level and LDH at the time of diagnosis were independent factors for a poor prognosis. Palliative local treatment improved survival better than chemotherapy alone in patients with 0, 1, 2, or 3 of the prognostic factors (p < 0.01). Patients administered treatment for pulmonary metastases survived longer than those treated for metastases elsewhere (56.77 vs. 35.43 months, p = 0.01). Surgical treatment provided marginally longer survival than non-surgical treatment (44.87 vs. 35.43 months, p = 0.05). These findings suggest palliative local treatment has survival benefit for selected patients with incurable metastatic colorectal cancer. PMID- 26992233 TI - An overview of long non-coding RNAs in ovarian cancers. AB - As with miRNAs a decade ago, the scientific community recently understood that lncRNAs represent a new layer of complexity in the regulation of gene expression. Although only a subset of lncRNAs has been functionally characterized, it is clear that they are deeply involved in the most critical physiological and pathological biological processes. This review shows that in ovarian carcinoma, data already available testify to the importance of lncRNAs and that the demonstration of an ever-growing role of lncRNAs in the biology of this malignancy can be expected from future studies. We also underline the importance of their relationship with associated protein partners and miRNAs. Together, the available information suggests that the emerging field of lncRNAs will pave the way for a better understanding of ovarian cancer biology and might lead to the development of innovative therapeutic approaches. Moreover, lncRNAs expression signatures either alone or in combination with other types of markers (miRNAs, mRNAs, proteins) could prove useful to predict outcome or treatment follow-up in order to improve the therapeutic care of ovarian carcinoma patients. PMID- 26992235 TI - Development and validation of a prognostic nomogram based on the log odds of positive lymph nodes (LODDS) for breast cancer. AB - BACKGROUND: To evaluate the prognostic effect of log odds of positive lymph nodes (LODDS) and develop a nomogram for survival prediction in breast cancer patients at the time of surgery. RESULTS: LODDS was an independent risk factor for cancer related death in breast cancer (hazard ratio: 1.582, 95%CI: 1.190-2.104). Menopausal status, tumor size, pathological lymph node staging, estrogen receptor status and human epidermal growth factor receptor-2 status were also included in the nomogram. The calibration plots indicated optimal agreement between the nomogram prediction and actual observation. Discrimination of nomogram was superior to the seventh edition TNM staging system [C-index: 0.745 vs. 0.721 (p = 0.03) in training cohort; 0.796 vs. 0.726 (p < 0.01) in validation cohort]. METHODS: We retrospectively evaluated 2023 breast cancer patients from Jan 2002 to Dec 2008 at our center. The cohort was randomly divided into training cohort and validation cohort. Univariate and multivariate analyses were performed to identify prognostic factors, and nomogram was established using Cox regression model in training cohort. External validation of the nomogram was performed in the validation cohort. CONCLUSIONS: The LODDS is an independent prognostic indicator in breast cancer and the novel nomogram can provide individual prediction of cancer-specific survival and help prognostic assessment for breast cancer patients. PMID- 26992236 TI - Cellular evidence for nano-scale exosome secretion and interactions with spermatozoa in the epididymis of the Chinese soft-shelled turtle, Pelodiscus sinensis. AB - The epididymis is the location of sperm maturation and sperm storage. Recent studies have shown that nano-scale exosomes play a vital role during these complicated processes. Our aim was to analyze the secretory properties of epididymal exosomes and their ultrastructural interaction with maturing spermatozoa in the Chinese soft-shelled turtle. The exosome marker CD63 was primarily localized to the apices of principal cells throughout the epididymal epithelium. Identification of nano-scale exosomes and their secretory processes were further investigated via transmission electron microscopy. The epithelium secreted epididymal exosomes (50~300 nm in diameter) through apocrine secretion and the multivesicular body (MVB) pathway. Spermatozoa absorbed epididymal exosomes through endocytosis or membrane fusion pathways. This study shows, for the first time, that nano-scale exosomes use two secretion and two absorption pathways in the reptile, which may be contribute to long-term sperm storage. PMID- 26992237 TI - Safety of two-year caloric restriction in non-obese healthy individuals. AB - BACKGROUND: The extent to which sustained caloric restriction (CR) in healthy non obese adults is safe has not been previously investigated. OBJECTIVE: Assess the safety and tolerability of sustained two-year CR intervention in healthy, non obese adults. DESIGN: A multi-center, randomized controlled trial. Participants were randomized using a 2:1 allocation in favor of 25% CR vs. Ad-Libitum intake (AL). Adverse and serious adverse events (AE, SAE), safety laboratory tests, and other safety parameters were closely monitored. RESULTS: Three participants were withdrawn from the CR intervention because of the safety concerns. No deaths and one SAE was reported by participants in the CR group. Although the difference in AE between AL and CR groups was not significant, within the CR group, the incidence of nervous system (p = 0.02), musculoskeletal (p = 0.02) and reproductive system (p = 0.002) disorders was significantly higher in the normal weight than in the overweight participants. At months 12 and 24, bone mineral densities at the lumbar spine, total hip, and femoral neck of participants in the CR group were significantly lower than in those in the AL group. CONCLUSIONS: Two years of CR at levels achieved in CALERIE was safe and well tolerated. Close monitoring for excessive bone loss and anemia is important. PMID- 26992238 TI - Decreased MALL expression negatively impacts colorectal cancer patient survival. AB - The aim of the present study was to determine whether MALL expression is associated with colon cancer progression and patient survival. MALL mRNA expression was reduced in the tumor tissues of 70% of the colon cancer patients and 75% of the rectal cancer patients as compared to their normal tissues. MALL protein was also significantly reduced in the tumor tissues of colon cancer patients (P < 0.001). Increased LOH and methylation of MALL was observed in tumor tissues as compared to normal tissues. Reduced MALL expression was associated with vessin invasion, disease recurrence and metastasis or death (P <= 0.027). Furthermore, patients with MALL-negative tumors had significantly decreased overall survival (OS) and disease-free survival (DFS) (P < 0.008 and P < 0.011, respectively). Univariate analysis indicated that MALL expression was significantly associated with OS and DFS. Finally, overexpression of MALL suppressed HCT116 and SW480 cell proliferation and inhibited HCT116 migration. MALL may play a role in colorectal cancer progression as suppression of its expression in tumor tissues negatively impacts colorectal cancer patient survival. Further analyses are required to determine if reduced MALL expression is due to LOH and/or methylation. PMID- 26992239 TI - MRP1-CD28 bi-specific oligonucleotide aptamers: target costimulation to drug resistant melanoma cancer stem cells. AB - In this work we show a clinically feasible strategy to convert in situ the own tumor into an endogenous vaccine by coating the melanoma cancerous cells with CD28 costimulatory ligands. This therapeutic approach is aimed at targeting T cell costimulation to chemotherapy-resistant tumors which are refractory and been considered as untreatable cancers. These tumors are usually defined by an enrichment of cancer stem cells and characterized by the higher expression of chemotherapy-resistant proteins. In this work we develop the first aptamer that targets chemotherapy-resistant tumors expressing MRP1 through a novel combinatorial peptide-cell SELEX. With the use of the MRP1 aptamer we engineer a MRP1-CD28 bivalent aptamer that is able to bind MRP1-expressing tumors and deliver the CD28 costimulatory signal to tumor-infiltrating lymphocytes. The bi specific aptamer is able to enhance costimulation in chemotherapy-resistant tumors. Melanoma-bearing mice systemically treated with MRP1-CD28 bivalent aptamer show reduced growth, thus proving an improved mice survival.Besides, we have designed a technically feasible and translational whole-cell vaccine (Aptvax). Disaggregated cells from tumors can be directly decorated with costimulatory ligand aptamers to generate the vaccine Aptvax. CD28Aptvax made of irradiated tumor cells coated with the CD28-agonistic aptamer attached to MRP1 elicits a strong tumor- cell immune response against melanoma tumors reducing tumor growth. PMID- 26992240 TI - Emetine induces chemosensitivity and reduces clonogenicity of acute myeloid leukemia cells. AB - Acute myeloid leukemia (AML) is an hematologic neoplasia characterized by the accumulation of transformed immature myeloid cells in bone marrow. Although the response rate to induction therapy is high, survival rate 5-year after diagnosis is still low, highlighting the necessity of new novel agents. To identify agents with the capability to abolish the self-renewal capacity of AML blasts, an in silico screening was performed to search for small molecules that induce terminal differentiation. Emetine, a hit compound, was validated for its anti-leukemic effect in vitro, ex vivo and in vivo. Emetine, a second-line anti-protozoa drug, differentially reduced cell viability and clonogenic capacity of AML primary patient samples, sparing healthy blood cells. Emetine treatment markedly reduced AML burden in bone marrow of xenotransplanted mice and decreased self-renewal capacity of the remaining engrafted AML cells. Emetine also synergized with commonly used chemotherapeutic agents such as ara-C. At a molecular level, emetine treatment was followed by a reduction in HIF-1alpha protein levels. This study validated the anti-leukemiceffect of emetine in AML cell lines, a group of diverse AML primary samples, and in a human AML-transplanted murine model, sparing healthy blood cells. The selective anti-leukemic effect of emetine together with the safety of the dose range required to exert this effect support the development of this agent in clinical practice. PMID- 26992241 TI - BAF180 regulates cellular senescence and hematopoietic stem cell homeostasis through p21. AB - BAF180 (also called PBRM1), a subunit of the SWI/SNF complex, plays critical roles in the regulation of chromatin remodeling and gene transcription, and is frequently mutated in several human cancers. However, the role of mammalian BAF180 in tumor suppression and tissue maintenance in vivo remains largely unknown. Here, using a conditional somatic knockout approach, we explored the cellular and organismal functions of BAF180 in mouse. BAF180 deletion in primary mouse embryonic fibroblasts (MEFs) triggers profound cell cycle arrest, premature cellular senescence, without affecting DNA damage response or chromosomal integrity. While somatic deletion of BAF180 in adult mice does not provoke tumor development, BAF180 deficient mice exhibit defects in hematopoietic system characterized by progressive reduction of hematopoietic stem cells (HSCs), defective long-term repopulating potential, and hematopoietic lineage developmental aberrations. BAF180 deletion results in elevated p21 expression in both MEFs and HSCs. Mechanistically, we showed that BAF180 binds to p21 promoter, and BAF180 deletion enhances the binding of modified histones associated with transcriptional activation on p21 promoter. Deletion of p21 rescues cell cycle arrest and premature senescence in BAF180 deficient MEFs, and partially rescues hematopoietic defects in BAF180 deficient mice. Together, our study identifies BAF180 as a critical regulator of cellular senescence and HSC homeostasis, which is at least partially regulated through BAF180-mediated suppression of p21 expression. Our results also suggest that senescence triggered by BAF180 inactivation may serve as a failsafe mechanism to restrain BAF180 deficiency associated tumor development, providing a conceptual framework to further understand BAF180 function in tumor biology. PMID- 26992243 TI - Characterization of a GEM-based scintillation detector with He-CF4 gas mixture in clinical proton beams. AB - Accurate, high-spatial resolution dosimetry in proton therapy is a time consuming task, and may be challenging in the case of small fields, due to the lack of adequate instrumentation. The purpose of this work is to develop a novel dose imaging detector with high spatial resolution and tissue equivalent response to dose in the Bragg peak, suitable for beam commissioning and quality assurance measurements. A scintillation gas electron multiplier (GEM) detector based on a double GEM amplification structure with optical readout was filled with a He/CF4 gas mixture and evaluated in pristine and modulated proton beams of several penetration ranges. The detector's performance was characterized in terms of linearity in dose rate, spatial resolution, short- and long-term stability and tissue-equivalence of response at different energies. Depth-dose profiles measured with the GEM detector in the 115-205 MeV energy range were compared with the profiles measured under similar conditions using the PinPoint 3D small-volume ion chamber. The GEM detector filled with a He-based mixture has a nearly tissue equivalent response in the proton beam and may become an attractive and efficient tool for high-resolution 2D and 3D dose imaging in proton dosimetry, and especially in small-field applications. PMID- 26992244 TI - Large scale study on the variation of RF energy absorption in the head & brain regions of adults and children and evaluation of the SAM phantom conservativeness. AB - This paper presents the results of two computational large scale studies using highly realistic exposure scenarios, MRI based human head and hand models, and two mobile phone models. The objectives are (i) to study the relevance of age when people are exposed to RF by comparing adult and child heads and (ii) to analyze and discuss the conservativeness of the SAM phantom for all age groups. Representative use conditions were simulated using detailed CAD models of two mobile phones operating between 900 MHz and 1950 MHz including configurations with the hand holding the phone, which were not considered in most previous studies. The peak spatial-average specific absorption rate (psSAR) in the head and the pinna tissues is assessed using anatomically accurate head and hand models. The first of the two mentioned studies involved nine head-, four hand- and two phone-models, the second study included six head-, four hand- and three simplified phone-models (over 400 configurations in total). In addition, both studies also evaluated the exposure using the SAM phantom. Results show no systematic differences between psSAR induced in the adult and child heads. The exposure level and its variation for different age groups may be different for particular phones, but no correlation between psSAR and model age was found. The psSAR from all exposure conditions was compared to the corresponding configurations using SAM, which was found to be conservative in the large majority of cases. PMID- 26992242 TI - Prostate tumor overexpressed-1, in conjunction with human papillomavirus status, predicts outcome in early-stage human laryngeal squamous cell carcinoma. AB - In human cancer, molecular markers combined with clinical characteristics are used increasingly to predict prognosis. Prostate tumor overexpressed-1 (PTOV1), first identified in prostate cancer, is a key factor in tumor progression and correlates with unfavorable clinical outcomes. HPV infection status was tested by HPV E6-targeted multiplex real-time PCR and p16 immunohistochemistry (IHC). Real time PCR and western blotting analyses were used to examine the mRNA and protein expression levels of PTOV1 in eight paired LSCC samples. IHC was performed to assess PTOV1 protein expression in 196 paraffin-embedded, archived LSCC samples. PTOV1 protein and mRNA expression was increased in LSCC tissues compared with adjacent non-cancerous tissue samples. High expression of PTOV1was significantly associated with advanced TNM stage by the chi2 test. Multivariate analysis revealed that PTOV1 and HPV status were independent prognostic indicators of overall survival (OS) and progression-free survival (PFS) (P = 0.001, P = 0.009 for OS, P = 0.005, P = 0.012 for PFS, respectively). Our study provides the first evidence that the combination of PTOV1 expression level and HPV status provides more prognostic information compared with HPV status alone with the significance still exists in the HPV negative subgroup. PMID- 26992245 TI - 3D-2D image registration for target localization in spine surgery: investigation of similarity metrics providing robustness to content mismatch. AB - In image-guided spine surgery, robust three-dimensional to two-dimensional (3D 2D) registration of preoperative computed tomography (CT) and intraoperative radiographs can be challenged by the image content mismatch associated with the presence of surgical instrumentation and implants as well as soft-tissue resection or deformation. This work investigates image similarity metrics in 3D 2D registration offering improved robustness against mismatch, thereby improving performance and reducing or eliminating the need for manual masking. The performance of four gradient-based image similarity metrics (gradient information (GI), gradient correlation (GC), gradient information with linear scaling (GS), and gradient orientation (GO)) with a multi-start optimization strategy was evaluated in an institutional review board-approved retrospective clinical study using 51 preoperative CT images and 115 intraoperative mobile radiographs. Registrations were tested with and without polygonal masks as a function of the number of multistarts employed during optimization. Registration accuracy was evaluated in terms of the projection distance error (PDE) and assessment of failure modes (PDE > 30 mm) that could impede reliable vertebral level localization. With manual polygonal masking and 200 multistarts, the GC and GO metrics exhibited robust performance with 0% gross failures and median PDE < 6.4 mm (+/-4.4 mm interquartile range (IQR)) and a median runtime of 84 s (plus upwards of 1-2 min for manual masking). Excluding manual polygonal masks and decreasing the number of multistarts to 50 caused the GC-based registration to fail at a rate of >14%; however, GO maintained robustness with a 0% gross failure rate. Overall, the GI, GC, and GS metrics were susceptible to registration errors associated with content mismatch, but GO provided robust registration (median PDE = 5.5 mm, 2.6 mm IQR) without manual masking and with an improved runtime (29.3 s). The GO metric improved the registration accuracy and robustness in the presence of strong image content mismatch. This capability could offer valuable assistance and decision support in spine level localization in a manner consistent with clinical workflow. PMID- 26992246 TI - Microsatellite Organization in the B Chromosome and A Chromosome Complement in Astyanax (Characiformes, Characidae) Species. AB - The organization of microsatellites in B and sex chromosomes has been linked to chromosomal evolution in a number of animal groups. Here, the chromosomal organizations of (CA)15, (GA)15, (CG)15, (GACA)4, and (GATA)8 microsatellites were examined in several Astyanax species with different diploid numbers: Astyanax mexicanus (2n = 50 + 1 B chromosome), A. altiparanae (2n = 50), A. marionae (2n = 48), A. fasciatus (2n = 46), and A. schubarti (2n = 36). The (CA)15 and (GA)15 microsatellites were dispersed across the chromosomes of A. altiparanae and A. fasciatus but were also observed as clusters (CA and GA for A. altiparanae, and CA for A. fasciatus). In A. marionae and A. schubarti, the (CA)15 and (GA)15 microsatellites were dispersed but were also observed as clustered signals and coincident with heterochromatic regions. In all 4 of these species, the (CG)15 and (GACA)4 microsatellites were dispersed across chromosomes, and the (GATA)8 microsatellite was co-localized with 5S rDNA. In A. mexicanus, the (CA)15, (GA)15, (CG)15, (GATA)8, and (GACA)4 microsatellites were weakly detected and dispersed across the chromosomes of the A complement. On the B chromosome, signals for the different microsatellites were weak, strong, absent, weak, and absent, respectively. The distribution of microsatellites and the locational relationship between microsatellites and 5S rDNA are discussed, and a possible evolutionary pathway is proposed for microsatellites in Astyanax. PMID- 26992247 TI - Frequency of Fluoride Dentifrice Use and Caries Lesions Inhibition and Repair. AB - The clinical relevance of the frequency of fluoride dentifrice (FD) use on enamel caries is based on evidence. However, the relative effect of FD on reduction of demineralization or enhancement of remineralization is unknown and the effect of frequency on root dentine caries has not been explored. The aim of this double blind, crossover, in situ study, which was conducted in 4 phases of 14 days each, was to evaluate the relationship between the frequency of FD use and enamel and root dentine de- and remineralization. Eighteen volunteers wore palatal appliances containing enamel and root dentine slabs, either sound or carious. Biofilm accumulation on the slab surface was allowed, and 20% sucrose solution was dripped 3 or 8 times per day on the carious and sound slabs, respectively. Volunteers used FD (1,100 MUg F/g) in the frequencies 0 (fluoride-placebo dentifrice), 1, 2 and 3 times per day. The demineralization and remineralization that occurred in sound or carious slabs was estimated by the percentage of surface hardness loss (%SHL) or recovery (%SHR). Loosely (CaF2) and firmly (FAp) bound fluoride concentrations were also determined. The relationship between the variables was analyzed by linear regression. The %SHL, CaF2 and FAp concentrations were a function of the frequency of FD use for enamel and dentine, but the %SHR was a function of the frequency of FD use only for enamel (p < 0.05). The results suggest that demineralization in enamel and root dentine is reduced in proportion to the frequency of FD use, but for remineralization the effect of the frequency of FD use was relevant only to enamel. PMID- 26992249 TI - Interpreting the Lactulose Breath Test for the Diagnosis of Small Intestinal Bacterial Overgrowth. AB - INTRODUCTION: Based on literature review, a positive lactulose breath test (LBT) for small intestinal bacterial overgrowth requires an initial peak value of hydrogen within 100 minutes of lactulose ingestion with a second peak before 180minutes. However, using scintigraphic monitoring of lactulose transit time, mean oral-cecal arrival time has been reported as 73minutes. The goal was to propose new criteria for analysing the LBT to overcome false positive interpretations. METHODS: LBTs from our referral center were interpreted as positive after ingestion of 10g of lactulose using the following approach for hydrogen concentrations: (1) The literature guidelines: greater than 20ppm from a baseline less than 10ppm achieved within 100minutes followed by a further rise of greater than 15ppm within 180minutes. (2) The proposed criteria: greater than 20ppm from a baseline less than 10ppm within either 60 or 80minutes followed by a further rise of greater than 15ppm during the 180-minute test. RESULTS: A total of 153 patients with symptoms suspicious for small-bowel bacterial overgrowth underwent testing. Of all, 26.1% patients tested positive by 100minutes, 11.8% patients tested positive by 60minutes and 18.3% patients tested positive by 80minutes. The percentage of positive LBTs at 60 and 80minutes was significantly lesser than for the 100minutes criteria (P < 0.05). CONCLUSIONS: The first hydrogen peak increase should occur by either 60 or 80minutes to increase the specificity of LBT for small intestinal bacterial overgrowth based on the reality of lactulose cecal arrival times. PMID- 26992248 TI - Ritonavir-boosted danoprevir plus peginterferon alfa-2a and ribavirin in Asian chronic hepatitis C patients with or without cirrhosis. AB - BACKGROUND AND AIM: Chronic hepatitis C is an important public health problem in Asia. We evaluated the safety, efficacy, and pharmacokinetics of fixed-dose ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin in treatment naive Asian patients with chronic hepatitis C virus (HCV) genotype (G)1 infection. METHODS: Treatment-naive G1 patients in Taiwan, Thailand, and Korea with serum HCV-RNA level >= 105 IU/mL received ritonavir-boosted danoprevir 125/100 mg twice daily plus peginterferon alfa-2a/ribavirin for either 12 (noncirrhotic patients: Arm A, n = 34) or 24 weeks (cirrhotic patients: Arm B, n = 27) in this phase II open-label study. Sustained virologic response was defined as HCV-RNA < 25 IU/mL 12 weeks after end of treatment (SVR12). RESULTS: Similar SVR12 rates were achieved in Arms A (88.2%; 95% confidence interval, 73.4-95.3%) and B (88.9%; 71.9-96.2%). Most patients had G1b infection, among whom SVR12 rates in Arms A and B were 96.7% and 91.7%, respectively. The overall SVR12 rate was 94.0% in noncirrhotic Taiwanese patients (100% in the subset of G1b patients). No patients withdrew for safety reasons. Three (11%) cirrhotic patients (Arm B) experienced serious adverse events, none of which was considered to be related to treatment. No Grade 3/4 alanine aminotransferase elevations were reported. The pharmacokinetic properties of danoprevir were broadly overlapping in noncirrhotic and cirrhotic patients both on Days 1 and 14. CONCLUSIONS: Ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin produced sustained virologic response rates > 90% after 12 weeks' treatment in noncirrhotic and 24 weeks' treatment in cirrhotic Asian patients with G1b infection and was well tolerated. These regimens are well suited to countries where G1b predominates. PMID- 26992250 TI - Relationships Between Illness Perceptions, Coping and Psychological Morbidity in Kidney Transplants Patients. AB - BACKGROUND: The aim of this study was to explore the effect of kidney transplantation (KT) on psychological distress and quality of life (QoL) in patients with end-stage kidney disease using the Common Sense Model of illness adjustment. MATERIALS AND METHODS: A total of 52 individuals (35 men and 17 women) with an average age of 53.54 years from a large metropolitan nephrology outpatient clinic participated. RESULTS: Poorer health status, illness perceptions and increased engagement in maladaptive coping were associated with psychological distress (specifically anxiety and depression) and poorer QoL. Hierarchical regression, after correcting for KT characteristics (years since most recent KT, number of transplants) indicated that poorer illness status and illness perception predicted QoL. After controlling for KT characteristics, poorer illness status and greater engagement in maladaptive coping predicted depression. In contrast, poorer illness perceptions and greater engagement in maladaptive coping predicted anxiety. Adaptive problem-focused and emotion focused coping styles were not found to predict anxiety, depression or QoL. CONCLUSIONS: The finding of the present study emphasize on the importance of exploring and understanding the effect of illness status, illness perceptions and coping patterns in patients who have underwent KT. PMID- 26992251 TI - Adult Common Variable Immunodeficiency. AB - BACKGROUND: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia, defective antibody production and recurrent upper and lower respiratory tract infections. The diagnosis in adult patients is often thought to be rare, and thus misdiagnosis often occurs. A limited number of cases of adult-onset CVID have been reported in China, and the features of the syndrome remain unclear. The objective of this study was to describe the main characteristics of CVID, and evaluate the treatment of adult patients who present with CVID. MATERIALS AND METHODS: This was a retrospective analysis of 8 patients with CVID from different departments in 1 center in China. Patients were diagnosed according to the diagnostic criteria of the European Society for Immunodeficiency Diseases. Demographics, clinical and immunological data from each patient were collected and a statistical analysis was undertaken. RESULTS: The mean age at diagnosis was 43 +/- 13.7 years, whereas the mean duration of diagnostic delay was 10.5 years. The median total serum levels of immunoglobulin (Ig) G, IgA and IgM at diagnosis were 2.5 +/- 0.59, 0.23 +/- 0.05 and 0.17 +/- 0.05g/L, respectively. A total of 7 patients also had a low CD4(+)/CD8(+) ratio. All patients presented with recurrent respiratory infections. Regular infusions of intravenous immunoglobulin every 3 weeks substantially reduced pneumonic episodes. CONCLUSIONS: Diagnosis is often delayed in adult CVID. Pulmonary infections and diseases were the most frequent presentations at onset of the disease. Regular intravenous immunoglobulin infusions were beneficial in controlling recurrent infections. PMID- 26992252 TI - Expression and Clinical Significance of Serum Dipeptidyl Peptidase IV Chronic Obstructive Pulmonary Disease. AB - OBJECTIVE: The purpose of this study is to explore the correlation between serum dipeptidyl peptidase IV (DPPIV) and chronic obstructive pulmonary disease (COPD) at its various disease states, analyze its applications in the prediction and diagnosis of COPD and test the possibility of DPPIV as the serologic marker for COPD screening. MATERIALS AND METHODS: Samples from 74 patients (42 cases with acute exacerbation of COPD or acute exacerbation COPD (AECOPD) and 32 cases with stable COPD) and 29 control subjects were collected in this study. Those patients with AECOPD were classified as COPD remission group if their clinical symptoms relieved after nonintravenous or oral hormone therapy for 7 +/- 3 days. DPPIV concentration was measured by enzyme-linked immunosorbent assay, and the difference in serum concentration of DPPIV was compared among different groups. The correlation between DPPIV concentration and age, sex or smoking history was analyzed, and the diagnostic value of DPPIV was evaluated by receiver-operating characteristic (ROC) curve analysis. RESULTS: Serum DPPIV concentration was significantly lower in all COPD groups as compared with that in healthy control group (P < 0.001). Serum DPPIV concentration in AECOPD group was increased after treatment (P < 0.001). There was no significant correlation between DPPIV concentration and age, sex or smoking history (P > 0.05). ROC analysis indicated that serum DPPIV concentration in all groups showed a good diagnostic accuracy, especially in stable COPD and AECOPD groups. The area under the ROC curve values were 0.901 and 0.906, respectively, with a high specificity of 0.931 for both groups and a high sensitivity of 0.75 for stable COPD and 0.875 for AECOPD. CONCLUSIONS: Serum DPPIV concentration in patients with COPD is decreased significantly, and there is no correlation between serum DPPIV concentration and sex or age. Serum DPPIV not only is an independent predictive factor, but also of high value as a good serologic marker for the diagnosis of COPD. PMID- 26992253 TI - Epidemiology of Rapidly Growing Mycobacteria Bloodstream Infections. AB - BACKGROUND: Rapidly growing mycobacteria (RGM) bloodstream infections (BSI) are an emerging problem often associated with therapeutic challenges. We review the epidemiology, treatment and outcomes over a 5-year period of a heterogeneous group presenting to our institution with RGM BSI. MATERIALS AND METHODS: A retrospective cohort study of patients with primary RGM BSI from January 2006 December 2011 was conducted. Patient characteristics (age, race, sex and comorbidities), infection characteristics (catheter associated, hospital acquired, microbiology and antimicrobial susceptibilities), therapy and outcomes were recorded and compared by species. RESULTS: Among 32 patients, 33 RGM BSI occurred. Patients had an average of 3-4 comorbidities, most commonly malignancy (45.5%). Most isolates (30.3%) were Mycobacterium fortuitum or Mycobacterium mucogenicum (27.2%), followed by Mycobacterium abscessus/chelonae (18.2%) and Mycobacterium immunogenum (12.2%). In all, 85% were catheter associated and 27.3% were hospital acquired. Empiric therapy was started in 19 (57.6%) patients and among these, it was adequate (at least 2 active agents based on susceptibilities) in 12 (63.2%). Among 21 patients with outcome data, cure was assumed for 14 (66.7%). One death was attributable to RGM BSI. Cure rates were higher among those who received adequate empiric therapy compared to those who did not (83.3% versus 42.9%). In general, antibiotic susceptibility was favorable across species for clarithromycin, amikacin and imipenem. CONCLUSIONS: RGM BSI occurred in a population with multiple comorbidities, most commonly malignancy, and most were catheter associated. Higher cures were seen among those who received adequate empiric therapy and based on susceptibility data, a broad empiric regimen of clarithromycin, amikacin and imipenem would be expected to be adequate. PMID- 26992254 TI - Insulin-Like Growth Factor-1 and Vascular Endothelial Growth Factor in Malignant and Benign Biliary Obstructions. AB - BACKGROUND: Despite the presence of various diagnostic tools, the differential diagnosis between malignant and benign biliary obstructions is so difficult. This study aimed to evaluate the role of serum and biliary insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) in this differential diagnosis. MATERIALS AND METHODS: Patients (n = 109, 61 men and 48 women) with diagnosis of benign (n = 62) or malignant (n = 47) biliary obstruction were included. Serum and biliary IGF-1 and VEGF markers were analyzed by the chemiluminescent immunometric method. RESULTS: Mean age was 62.7 +/- 8.1 years for the malignant group and 58.5 +/- 15.4 years for the benign group (P = 0.092). Choledocholithiasis (79%), cancer head of the pancreas (53.2%) and cholangiocarcinoma (38.3%) were the most common etiologies. No statistical difference was detected regarding serum IGF-1 and VEGF levels between 2 groups. At a cutoff value of 308.55 and 0.5ng/mL, biliary IGF-1 and VEGF had (91.4% and 90.3%) sensitivity and (89.5% and 84.9%) specificity differential diagnosis between malignant and benign biliary obstructions (area under the curve: 0.943, 0.915), respectively. CONCLUSIONS: Biliary levels of IGF-1 and VEGF significantly increase in malignant than benign obstructive lesions. Measurement of these markers in the bile of these patients may aid in the detection of biliary tumors. PMID- 26992255 TI - In vitro Synergistic Activity of Caspofungin Plus Polymyxin B Against Fluconazole Resistant Candida glabrata. AB - BACKGROUND: Candida species account for most invasive fungal infections, and the emergence of fluconazole and caspofungin resistance is problematic. Overcoming resistance with synergism between 2 drugs may be useful. In a 2013 in vitro study, caspofungin plus colistin (polymyxin E) was found to act synergistically against fluconazole-resistant and susceptible Candida albicans isolates. The purpose of our study was to extend this finding by evaluating caspofungin plus polymyxin B for in vitro synergy against fluconazole-resistant Candida glabrata isolates. MATERIALS AND METHODS: A total of 7 fluconazole-resistant C. glabrata bloodstream infection isolates were obtained from 2010-2011. Of these, 2 isolates were also resistant to caspofungin. Minimum inhibitory concentrations (MICs) for caspofungin and polymyxin B were determined by Etest and broth microdilution. Clinical and Laboratory Standards Institute breakpoints were used for fluconazole and caspofungin MIC interpretations. No interpretive guidelines exist for testing polymyxin B against C. glabrata. Synergy testing with caspofungin (1 * MIC) and polymyxin B (1/2MIC) was performed using a modified bacterial Etest synergy method and time-kill assay. RESULTS: With the Etest synergy method, 4 out of 7 isolates showed in vitro synergy and 1 out of 7 showed additivity. The remaining isolates (both caspofungin resistant) showed indifference. Using the time-kill assay, 1 out of 7 isolates showed synergy, 1 showed additivity and the remaining 5 (including both caspofungin-resistant isolates) showed indifference. CONCLUSIONS: Caspofungin susceptibility may be required for synergism between caspofungin and polymyxin B. Further synergy testing with caspofungin plus polymyxin B and additional fluconazole-resistant C. glabrata isolates should be performed. In vitro synergy/additivity may or may not correlate with in vivo benefit. PMID- 26992256 TI - Risk Factors and Prognostic Role of Left Atrial Enlargement in Patients with Cardiac Light-Chain Amyloidosis. AB - BACKGROUND: Light-chain amyloidosis (AL) is a plasma cell disorder characterized by the extracellular deposition of insoluble fibril-forming monoclonal immunoglobulin, aggregating in heart and leading to cardiac amyloidosis (CA). Transthoracic echocardiography is a noninvasive method used for the evaluation of cardiac diastolic dysfunction. The left atrium (LA) plays an important role in modulating cardiovascular performance, with its function participating left ventricular filling and its size being affected by diastolic function. Therefore, we aimed to assess prognostic values of LA size measured by a simple echocardiographic parameter, LA diameter indexed to body surface area, in CA and to explore risk factors associated with LA enlargement as well as the incidence of severe heart failure (HF). MATERIALS AND METHODS: A retrospective analysis of echocardiography of patients with biopsy-proven cardiac AL amyloidosis was conducted. LA enlargement was defined as LA diameter indexed to body surface area greater than 23mm/m(2). RESULTS: A total of 104 patients with CA were included in the final analysis, 61 (58.7%) of which showed a presentation of LA enlargement. Age, New York Heart Association, ejection fraction and early-to-atrial transmitral flow velocity ratio were independently associated with LA enlargement. During a mean follow-up period of 39 months, LA enlargement was strongly related with all-cause mortality (hazard ratio = 1.94; 95% CI: 1.14 3.29; P = 0.015) and increased risk of severe HF (hazard ratio = 2.18; 95% CI: 1.12-4.23; P = 0.022). CONCLUSIONS: In cardiac AL amyloidosis, age and early-to atrial transmitral flow velocity ratio were main independent risk factors with regard to LA enlargement. LA enlargement was strongly associated with incidence of severe HF and was also a significant predictor of all-cause mortality. PMID- 26992257 TI - Virulence Factors in Staphylococci Isolated From Nasal Cavities of Footballers. AB - AIM: This study aimed to investigate the rate of Panton-Valentine Leukocidin producing Staphylococcus aureus and methicillin (mecA) and slime (icaA/icaD) genes in staphylococcal strains isolated from nasal cavities of footballers. MATERIALS AND METHODS: Nasal swab samples were taken from each footballers and a healthy control group for the isolation of staphylococcal strains. The polymerase chain reaction technique was used to determine Panton-Valentine Leukocidin, mecA and icaA/icaD genes in staphylococcal isolates. RESULTS: Among 91 S. aureus strains, the presence of mecA gene was detected as 9.9%. This ratio was 17.9% (27 of 151) among the coagulase-negative staphylococci. A significant difference was found between coagulase-negative staphylococci and S. aureus isolates regarding the presence of mecA gene (P < 0.001). As for the genes of the slime, icaA/icaD genes were detected in 198 of 242 (81.8%) strains. The occurrence of slime genes was 91.2% and 89.4% among the S. aureus coagulase and negative staphylococci, respectively (P > 0.05). There was a statistically significant difference between the frequency of the mecA and slime genes when compared with the healthy control group and the football players (P < 0.01). Of 91 isolates, 22 were found to be methicillin resistant by the oxacillin disc diffusion method, whereas the remaining (220) were methicillin susceptible. Methicillin resistance was detected as 14.9% by the polymerase chain reaction method, whereas it was found as 9.1% by phenotypic methods. CONCLUSIONS: Early and accurate diagnosis of virulent staphylococcal strains is crucial because the virulent coagulase-negative and coagulase-positive staphylococcal strains in the nasal floras of footballers may be major potential sources of superficial and deep tissue infections. PMID- 26992258 TI - Curcumin Rescues Diabetic Renal Fibrosis by Targeting Superoxide-Mediated Wnt Signaling Pathways. AB - The purposes of this study were to investigate whether curcumin can weaken diabetic nephropathy by modulating both oxidative stress and renal injury from Wnt signaling mediation. Wnt5a/beta-catenin depression and induction of superoxide synthesis are associated with high glucose (HG) induced transforming growth factor (TGF)-beta1 and fibronectin expression in mesangial cells. Curcumin resumes HG depression of Wnt/beta-catenin signaling and alleviates HG induction of superoxide, TGF-beta1 and fibronectin expression in renal mesangial cell. Exogenous curcumin alleviated urinary total proteinuria and serum superoxide level in diabetic rats. Based on laser-captured microdissection for quantitative real-time polymerase chain reaction, it was found that diabetes significantly increased TGF-beta1 and fibronectin expression in line with depressed Wnt5a expression. Curcumin treatment reduced the TGF-beta1 and fibronectin activation and the inhibiting effect of diabetes on Wnt5a/beta-catenin expression in renal glomeruli. Immunohistochemistry showed that curcumin treatment significantly reduced 8-hydroxy-2'-deoxyguanosine, TGF-beta1 and fibronectin, and was in line with the restoration of the suppressed Wnt5a expression immunoreactivities in glomeruli of diabetic rats. Curcumin alleviated extracellular matrix accumulation in diabetic nephropathy by not only preventing the diabetes-mediated superoxide synthesis but also resuming downregulation of Wnt/beta-catenin signaling. These findings suggest that regulation of Wnt activity by curcumin is a feasible alternative strategy to rescue diabetic renal injury. PMID- 26992259 TI - An Uncommon Image of Spleen. PMID- 26992260 TI - Klebsiella pneumoniae Liver Abscess: An Emerging Disease. AB - Most of the cases of Klebsiella pneumoniae liver abscess reported early on were from Asia, predominantly Taiwan, with a significant number of patients being middle aged diabetic men, and developing metastatic complications, especially endophthalmitis. The entity is now being increasingly recognized in the United States. In this article, the authors review those reported cases, and also the literature regarding the pathophysiology of this intriguing syndrome. PMID- 26992261 TI - Medical Education Grand Rounds. PMID- 26992262 TI - Sitting for Picasso: Surprise and the Art of Medical Education. PMID- 26992263 TI - Fast-Growing Plasmacytoma. PMID- 26992264 TI - Effects of Renin-Angiotensin-Aldosterone System Blockade in Patients with End Stage Renal Disease. AB - Blockers of the renin-angiotensin-aldosterone system (RAAS), such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers are routinely used in patients with chronic kidney disease because of their cardiovascular (CV) and renoprotective effects. However, there are no uniform recommendations about RAAS blockers for CV protection in the end-stage renal disease (ESRD) population other than the preferred drug class for blood pressure control. This uncertainty stems from the fact that patients with ESRD were generally excluded from randomized controlled trials evaluating the cardioprotective benefits of RAAS blockers. It is important to weigh the potential harms associated with the use of RAAS blockers, such as electrolyte disturbances and worsening anemia, with their role in protection of residual kidney function, alleviation of thirst and potential CV benefits. The objective of this review is to summarize the current knowledge about the use of RAAS blockers in patients with ESRD. PMID- 26992265 TI - An Unusual Case of Acute Promyelocytic Leukemia Presenting With Hypoplastic Bone Marrow and Pancytopenia. PMID- 26992266 TI - Lichen Sclerosus in a Patient With a History of Hereditary Nonpolyposis Colorectal Cancer. PMID- 26992267 TI - Tophaceous Gout in the Nasal Root: An Unusual Initial Presentation. PMID- 26992268 TI - The Greatest Hematologist in the World. PMID- 26992269 TI - Type 4 Hiatal Hernia. PMID- 26992270 TI - Contribution of catastrophizing to disability and pain intensity after osteoporotic vertebral compression fracture. AB - BACKGROUND: Pain catastrophizing is a key variable that contributes to disability not only in chronic pain disorders but also after trauma. However, there is little evidence concerning the effect of catastrophizing on pain intensity and disability after osteoporotic vertebral compression fracture. Therefore, the purpose of this study was to evaluate the contribution of catastrophizing to disability and pain intensity after osteoporotic vertebral compression fracture. METHOD: We analyzed 35 patients with acute single-level osteoporotic vertebral compression fractures within 3 days of trauma. Data on demographics, education level, Charlson comorbidity index, pain catastrophizing scale (PCS) score, visual analog scale (VAS) score for back pain, and Oswestry Disability Index (ODI) were collected. VAS score for back pain and ODI were assessed at enrollment as well as at 2, 6, and 12 weeks after fracture. RESULTS: Each VAS score for back pain and ODI significantly improved compared to the initial values (P < 0.001). Among the independent variables, age and/or PCS score significantly correlated with VAS score for back pain and/or ODI over follow-up assessments. Hierarchical regression analysis finally showed that PCS score was a significant predictor for disability only in the acute period such as immediately and 2 weeks after fracture, whereas age was significantly associated with ODI at 6 and 12 weeks after fracture. CONCLUSIONS: The present study shows that catastrophizing can contribute to disability only in the acute period after osteoporotic vertebral compression fracture. As the compression fracture heals, however, age is the critical determinant of disability. PMID- 26992271 TI - Randomized trial of standard pain control with or without gabapentin for pain related to radiation-induced mucositis in head and neck cancer. AB - OBJECTIVE: Radiation-induced mucositis (RIM) in chemoradiotherapy (CRT) for head and neck cancer (HNC) causes severe pain and worsens CRT compliance, QOL and outcome. Following retrospective reports, we conducted a randomized trial of the safety and efficacy of gabapentin for RIM-associated pain during CRT. METHODS: HNC patients (pts) receiving CRT were randomized to standard pain control (SPC) with acetaminophen and opioids, or SPC plus gabapentin (SPC+G). Gabapentin was maintained at 900mg/day for 4 weeks after CRT. Primary endpoint was maximum visual analogue scale (VAS) score during CRT, and secondary endpoints were total opioid dose, changes in QOL (EORTC QLQ-C30 and QLQ-HN 35) from baseline to 4 weeks after CRT, and adverse events. RESULTS: Twenty-two eligible Stage III or IV pts were randomly assigned to SPC or SPC+G (n=11 each). Twelve were treated in a locally advanced setting and 10 in a postoperative setting. Median maximum VAS scores, median total dose of opioids at maximum VAS and total dose of opioids at 4 weeks after CRT tended to be higher in the SPC+G arm (47 in SPC vs. 74 in SPC+G, p=0.517; 215mg vs. 745.3mg, p=0.880; and 1260mg vs. 1537.5mg, p=0.9438, respectively), without significance. QOL analysis showed significantly worse scores in the SPC+G arm for weight gain (p=0.005). Adverse events related to gabapentin were manageable. CONCLUSIONS: This pilot study is the first prospective randomized trial of gabapentin for RIM-related pain. Gabapentin had no apparent beneficial effect. Further research into agents for RIM-related pain is warranted. PMID- 26992272 TI - Middle ear capillary haemangioma: Review of literature and appraisal of management options. AB - Infantile middle ear capillary haemangiomas (MECH) are a rare entity with only five reported cases in the literature. At present there is no consensus regarding the management of such lesions. Extra-cutaneous haemangiomas have been successfully managed with oral propranolol but not yet reported in MECH. We present a further case and appraise the management options. At present oral propranolol has not been used in the treatment of MECH. The literature suggests that infantile MECH have a higher propensity to spontaneously involute and a greater likelihood of response to propranolol. Surgical excision is the best option in older children and adults. PMID- 26992273 TI - Generation and usage of aequorin lentiviral vectors for Ca(2+) measurement in sub cellular compartments of hard-to-transfect cells. AB - Targeted aequorin-based Ca(2+) probes represent an unprecedented tool for the reliable measurement of Ca(2+) concentration and dynamics in different sub cellular compartments. The main advantages of aequorin are its proteinaceous nature, which allows attachment of a signal peptide for targeting aequorin to virtually any sub-cellular compartment; its low Ca(2+)-binding capacity; the wide range of Ca(2+) concentrations that can be measured, ranging from sub-micromolar to millimolar; its robust performance in aggressive environments, e.g., the strong acidic pH of the lysosomal lumen. Lentiviral vectors represent a popular tool to transduce post-mitotic or hard-to-transfect cells both in vitro and in vivo. Furthermore, it has great potential for gene therapy. Last generation lentiviral vectors represent a perfect compromise for combining large insert size, ease of production and handling, and high degree of biosafety. Here, we describe strategies for cloning aequorin probes - targeted to the cytosol, sub plasma membrane cytosolic domains, the mitochondrial matrix, and the endoplasmic reticulum lumen - into lentiviral vectors. We describe methods for the production of lentiviral particles, and provide examples of measuring Ca(2+) dynamics by such aequorin-encoding lentiviral vectors in sub-cellular compartments of hard-to transfect cells, including immortalized striatal neurons, primary cerebellar granule neurons and endothelial progenitor cells, which provide suitable in vitro models for the study of different human diseases. PMID- 26992274 TI - [Vision, knowledge, sensitiviyy and research: Essential components to advance in elderly care]. PMID- 26992275 TI - Submucous cleft palate: outcomes after primary repair with repositioning of the levator muscle in 51 consecutive patients. AB - I report the incidence of hypernasal resonance, nasal emission, and fistula after intravelar surgery with retropositioning of the levator muscle by a single surgeon in a consecutive series of 51 patients who presented with symptomatic submucous cleft palate. Intravelar veloplasty with repositioning of the levator muscle was highly effective in that 37/51 patients (73%) achieved either normal or mild and inconsistent resonance (p<0.0001), and 39 (77%) normal or mild and inconsistent nasal emissions (p<0.0001). The fistula rate was 6% (n=3). Both the clinical grade of submucous cleft palate and the presence of a syndrome correlated directly with changes in hypernasality, whereas the age of the patient and the degree of hypernasality at presentation did not. Non-syndromic patients with clinical grade III and II submucous cleft palates responded well to intravelar surgery with repositioning of the levator muscle, and routine preoperative videofluoroscopy is not recommended. I recommend intravelar surgery with repositioning of the levator muscle routinely for all non-syndromic patients who present with grade III or II submucous cleft palate and velopharyngeal insufficiency. PMID- 26992276 TI - Non-ionizing real-time ultrasonography in implant and oral surgery: A feasibility study. AB - PURPOSE: Ultrasound imaging has potential to complement radiographic imaging modalities in implant and oral surgery given that it is non-ionizing and provides instantaneous images of anatomical structures. For application in oral and dental imaging, its qualities are dependent on its ability to accurately capture these complex structures. Therefore, the aim of this feasibility study was to investigate ultrasound to image soft tissue, hard tissue surface topography and specific vital structures. MATERIAL AND METHODS: A clinical ultrasound scanner, paired with two 14-MHz transducers of different sizes (one for extraoral and the other for intraoral scans), was used to scan the following structures on a fresh cadaver: (i) the facial bone surface and soft tissue of maxillary anterior teeth, (ii) the greater palatine foramen; (iii) the mental foramen and (iv) the lingual nerve. Multiple measurements relevant to these structures were made on the ultrasound images and compared to those on cone-beam computed tomography (CBCT) scans and/or direct measurements. RESULTS: Ultrasound imaging could delineate hard tissue surfaces, including enamel, root dentin and bone as well as soft tissue with high resolution (110 MUm wavelength). The greater palatine foramen, mental foramen and lingual nerve were clearly shown in ultrasound images. Merging ultrasound and CBCT images demonstrated overall spatial accuracy of ultrasound images, which was corroborated by data gathered from direct measurements. CONCLUSION: For the first time, this study provides proof-of-concept evidence that ultrasound can be a real-time and non-invasive alternative for the evaluation of oral and dental anatomical structures relevant for implant and oral surgery. PMID- 26992277 TI - Observational Studies to Contextualize Surgical Trials. PMID- 26992278 TI - Mode of Delivery: A Modifiable Risk Factor for Subsequent Stress Urinary Incontinence? PMID- 26992279 TI - Reply to Nicola Fossati, Giorgio Gandaglia, Alberto Bossi, Francesco Montorsi, Alberto Briganti's Letter to the Editor re: Stephen J. Freedland, Voleak Choeurng, Lauren Howard, et al. Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy After Radical Prostatectomy. Eur Urol 2016;70:588-96. PMID- 26992280 TI - Re: Mark W. Ball, Nathaniel Readal, Phillip M. Pierorazio, Mohamad E. Allaf. Splitting One Kidney into Two: Robotic Partial Kidney Transplant in a Porcine Model. Eur Urol 2016;69:968-9. PMID- 26992281 TI - Prednisone Use in Conjunction with Abiraterone Acetate: Is Patient Safety a Concern with Long-term Steroid Exposure? PMID- 26992282 TI - Re: Stephen J. Freedland, Voleak Choeurng, Lauren Howard, et al. Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy. Eur Urol 2016;70:588-96: Testing the Utility of Genomic Scores in the Setting of Recurrent Prostate Cancer After Radical Prostatectomy: We Can Certainly Do Better. PMID- 26992283 TI - The utility of positron emission tomography with and without computed tomography in patients with nonmelanoma skin cancer. AB - Combined positron emission tomography (PET) and computed tomography (CT) scans are widely used in the staging and monitoring of most malignancies. The differential for PET-positive cutaneous lesions includes primary skin cancers, infections, cutaneous metastases from distant malignancies, and benign neoplasms. In dermatology, PET/CT scans have been most widely studied in patients with melanoma and Merkel cell carcinoma. The role of PET/CT scans in the management of other cutaneous malignancies is less clear, but it has shown great promise in the management of patients with squamous cell carcinoma and cutaneous lymphoma. This review seeks to address the usefulness of PET/CT scans in nonmelanoma skin cancer and to provide guidance regarding the management of patients with incidental PET positive nodules. Currently, there is limited experience with PET/CT scans for staging and monitoring of non-head and neck metastatic basal cell and squamous cell carcinomas, and results show limited sensitivity and specificity. We also address the evidence for management of an incidental PET-positive cutaneous nodule and recommend obtaining a biopsy specimen in patients with a known noncutaneous malignancy, a history of primary skin cancer, or a high risk of either cutaneous or noncutaneous malignancy. PMID- 26992284 TI - How we may think: Imaging and writing technologies across the history of the neurosciences. AB - In the neurosciences, two alternative regimes of visualization can be differentiated: anatomical preparations for morphological images and physiological studies for functional representations. Adapting a distinction proposed by Peter Galison, this duality of visualization regimes is analyzed here as the contrast between an imaging and a writing approach: the imaging approach, focusing on mimetic representations, preserving material and spatial relations, and the writing approach as used in physiological studies, retaining functional relations. After a dominance of morphological images gathering iconic representations of brains and architectural brain theories, the advent of electroencephalography advanced writing approaches with their indexical signs. Addressing the brain allegedly at its mode of operation, electroencephalography was conceived as recording the brain's intrinsic language, extending the writing approach to include symbolic signs. The availability of functional neuroimaging signaled an opportunity to overcome the duality of imaging and writing, but revived initially a phrenological conflation of form and function, suppressing the writing approach in relation to imaging. More sophisticated visualization modes, however, converted this reductionism to the ontological productivity of social neuroscience and recuperated the theorizing from the writing approach. In light of the ongoing instrumental mediations between brains, data and theories, the question of how we may think, once proposed by Vannevar Bush as a prospect of enhanced human-machine interaction, has become the state of affairs in the entanglements of instruments and organic worlds. PMID- 26992285 TI - It is what it eats: Chemically defined media and the history of surrounds. AB - The cultivation of living organs, cells, animals, and embryos in the laboratory has been central to the production of biological knowledge. Over the twentieth century, the drive to variance control in the experimental setting led to systematic efforts to generate synthetic, chemically defined substitutes for complex natural foods, housing, and other substrates of life. This article takes up the history of chemically defined media with three aims in mind. First, to characterize patterns of decontextualization, tinkering, and negotiation between life and experimenter that occur across disparate histories of cultivation. Second, to highlight the paradoxical historicity of cultivated organisms generated to be freed from context, as they incorporate and embody the purified amino acids, vitamins, plastics, and other artificial supports developed in the name of experimental control. Third, to highlight the figure-ground reversal that occurs as these cells and organisms are reconsidered as accidentally good models of life in industrialized conditions of pollution and nutrient excess, due to the man-made nature of their surrounds. Methodologically, the history of surrounds is described as an epigenetic approach that focuses on the material relations between different objects and organisms previously considered quite separately, from explanted organs to bacteria to plant cells to rats to human embryos. PMID- 26992286 TI - Statin Use and the Risk for Incident Diabetes Mellitus in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Population-Based Retrospective Cohort Study in Taiwan. AB - OBJECTIVES: The purpose of this study was to examine the association between statin use by individuals and the risk for incident diabetes mellitus in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). METHODS: We conducted a retrospective cohort study of patients who were hospitalized for ACS between January 1, 2006, and December 31, 2010, and who had undergone PCI (n=30,665); the data were retrieved from the Taiwan National Health Insurance Research Database. A propensity score technique was used to establish a 1:1 matched cohort for statin users and non-statin users (n=9043 for each group). The risk for incident diabetes mellitus in statin users compared to non-statin users for patients with ACS after PCI was estimated by the multivariable Cox proportional hazards regression model. RESULTS: Statin use was associated with a significant increase of 27% in the risk for new-onset diabetes mellitus (adjusted hazard ratio [HR] 1.27, 95% CI 1.14 to 1.41) compared to non-statin use in the matched cohort. The matched cohort analysis indicated that almost all individual statins were associated with a statistically significant increase in the risk for new-onset diabetes mellitus compared to those without statin use. CONCLUSIONS: Our study indicated an association between increased risk for new-onset diabetes mellitus and statin use. Because the benefits of statins in prevention of morbidity and mortality in patients with ACS are well-established, clinical decision making should not be changed for patients with existing cardiovascular disease in whom statin therapy is recommended. PMID- 26992287 TI - Knowledge Confidence and Desire for Further Diabetes-Management Education among Nurses and Personal Support Workers in Long-Term Care. AB - BACKGROUND: Diabetes care in the long-term care (LTC) setting is complicated by increased prevalence of comorbidities, age-related changes in medication tolerance, frailty and limited resources. Registered nurses (RNs), registered practical nurses (RPNs) and personal support workers (PSWs) are responsible for front-line diabetes care; however, there is limited formal diabetes education in this setting. PURPOSE: The current study aimed to assess the knowledge confidence and desire for additional diabetes education among nurses and PSWs in the LTC setting. METHODS: We studied 89 RNs, RPNs and PSWs (Mage=43.6, 94.3% female) in 2 LTC facilities in the Kitchener-Waterloo area who participated in an online survey assessing knowledge and confidence in 6 key areas of diabetes care (nutrition, insulin, oral medications, hypoglycemia, hyperglycemia and sick-day management). Interest in further diabetes education was also explored. RESULTS: Self-rated knowledge and confidence were generally moderate to high, ranging from 46% to 79% being moderately to very knowledgeable and from 61% to 74% being moderately to very confident. Knowledge and confidence was highest for nutrition and management of hypo- and hyperglycemia and lower for sick-day management, oral medications and insulin. There were significant differences between clinicians such that PSWs reported less knowledge and confidence than RNs and RPNs on most parameters. Among the whole sample, 85% wanted education about diabetes, and this rate did not vary by occupation. The most commonly reported areas for additional education concerning diabetes were for management of hypo- and hyperglycemia (30% to 31%) and insulin (31%). CONCLUSION: Overall, the findings indicate moderate levels of self-rated knowledge across diabetes care areas; however, most clinicians feel there is room for more diabetes-care education, particularly regarding insulin and management of hypo- and hyperglycemia. PMID- 26992289 TI - Synthesis and evaluation of novel lipopeptide as a vehicle for efficient gene delivery and gene silencing. AB - Nucleic acid-based therapeutics have recently emerged as a new class of next generation agents for treatment and prevention of viral infection, cancer, and genetic disorders, but their wide use is limited by their relatively weak delivery into target cells. Usage of synthetic cationic amphiphiles with peptide hydrophilic domain as agents for non-viral gene delivery is an attractive approach. We developed the schemes for the synthesis of aliphatic peptides with different length of the hydrocarbon chains in hydrophobic domains and different amino acids in polar head. For the obtained derivatives we determined transfection efficiency, critical vesicle concentration, particle size, zeta potential and aggregates stability. We have found that the transfection efficiency is increased if the ornithine is a part of polar head in an amphiphile. The most promising amphiphile for liposomal formation OrnOrnGlu(C16H33)2 was examined more carefully. It has been shown that the lipopeptide possesses low toxicity (in vitro and in vivo) and high transfection efficiency with pDNA and siRNA in different cell lines. In addition, the production of liposomes based on this lipopeptide is simple, quick and cheap. Thus OrnOrnGlu(C16H33)2 is a promising vehicle for gene delivery and gene silencing. PMID- 26992290 TI - Uncertainty analysis as essential step in the establishment of the dynamic Design Space of primary drying during freeze-drying. AB - Large molecules, such as biopharmaceuticals, are considered the key driver of growth for the pharmaceutical industry. Freeze-drying is the preferred way to stabilise these products when needed. However, it is an expensive, inefficient, time- and energy-consuming process. During freeze-drying, there are only two main process variables to be set, i.e. the shelf temperature and the chamber pressure, however preferably in a dynamic way. This manuscript focuses on the essential use of uncertainty analysis for the determination and experimental verification of the dynamic primary drying Design Space for pharmaceutical freeze-drying. Traditionally, the chamber pressure and shelf temperature are kept constant during primary drying, leading to less optimal process conditions. In this paper it is demonstrated how a mechanistic model of the primary drying step gives the opportunity to determine the optimal dynamic values for both process variables during processing, resulting in a dynamic Design Space with a well-known risk of failure. This allows running the primary drying process step as time efficient as possible, hereby guaranteeing that the temperature at the sublimation front does not exceed the collapse temperature. The Design Space is the multidimensional combination and interaction of input variables and process parameters leading to the expected product specifications with a controlled (i.e., high) probability. Therefore, inclusion of parameter uncertainty is an essential part in the definition of the Design Space, although it is often neglected. To quantitatively assess the inherent uncertainty on the parameters of the mechanistic model, an uncertainty analysis was performed to establish the borders of the dynamic Design Space, i.e. a time-varying shelf temperature and chamber pressure, associated with a specific risk of failure. A risk of failure acceptance level of 0.01%, i.e. a 'zero-failure' situation, results in an increased primary drying process time compared to the deterministic dynamic Design Space; however, the risk of failure is under control. Experimental verification revealed that only a risk of failure acceptance level of 0.01% yielded a guaranteed zero-defect quality end product. The computed process settings with a risk of failure acceptance level of 0.01% resulted in a decrease of more than half of the primary drying time in comparison with a regular, conservative cycle with fixed settings. PMID- 26992288 TI - Granulocyte colony-stimulating factor (G-CSF) upregulates beta1 integrin and increases migration of human trophoblast Swan 71 cells via PI3K and MAPK activation. AB - Multiple cytokines and growth factors expressed at the fetal-maternal interface are involved in the regulation of trophoblast functions and placental growth, but the role of G-CSF has not been completely established. Based on our previous study showing that G-CSF increases the activity of matrix metalloproteinase-2 and the release of vascular endothelial growth factor in Swan 71 human trophoblast cells, in this work we explore the possible contribution of G-CSF to cell migration and the G-CSF-triggered signaling pathway. We found that G-CSF induced morphological changes on actin cytoskeleton consistent with a migratory cell phenotype. G-CSF also up-regulated the expression levels of beta1 integrin and promoted Swan 71 cell migration. By using selective pharmacological inhibitors and dominant negative mutants we showed that PI3K, Erk 1/2 and p38 pathways are required for promoting Swan 71 cell motility. It was also demonstrated that PI3K behaved as an upstream regulator of Erk 1/2 and p38 MAPK. In addition, the increase of beta1 integrin expression was dependent on PI3K activation. In conclusion, our results indicate that G-CSF stimulates beta1 integrin expression and Swan 71 cell migration by activating PI3K and MAPK signaling pathways, suggesting that G-CSF should be considered as an additional regulatory factor that contributes to a successful embryo implantation and to the placenta development. PMID- 26992291 TI - Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies. AB - A number of intravenous immunoglobulin preparations are stabilized with sugar additives that may lead over time to undesirable glycation reactions especially in liquid formulation. This study aimed to evaluate the reactivity of sugar excipients on such preparations in condition of temperature, formulation and concentration commonly used for pharmaceutical products. Through an innovative LC MS method reported to characterize post-translational modifications of IgGs Fc/2 fragments, a stability study of IVIg formulated with reducing and non-reducing sugars has been undertaken. The rate of polyclonal IgGs glycation was investigated during 6months at 5, 25, 30 and 40 degrees C. High levels of glycation were observed with reducing sugars such as glucose and maltose in the first months of the stability study from 25 degrees C. Non-reducing sugars presented a low reactivity even at the highest tested temperature (40 degrees C). Furthermore, a site by site analysis was performed by MS/MS to determine the glycation sites which were mainly identified at Lys246, Lys248 and Lys324. This work points out the high probability of glycation reactions in some commercialized products and describes a useful method to characterize IVIg glycated products issued from reducing sugar excipients. PMID- 26992292 TI - Lichen planus of the lips: an intermediate disease between the skin and mucosa? Retrospective clinical study and review of the literature. AB - BACKGROUND: Lichen planus of the lips (LPL) is not frequently described in the literature. The objective of this study is to investigate the clinical outline, behavior, and prognosis of LPL. METHODS: Clinical data of patients with true oral lichen planus (LP) involving the lips, diagnosed and treated at our Oral Medicine Unit (University Federico II of Naples, Italy), have been collected and analyzed. Concurrently, a PubMed search was carried out from 1950 to March 2014 to assess epidemiological and clinical data about LPL. RESULTS: Our case series revealed 13 patients (female/male ratio 0.4) with a mean (+/- SD) age of 71.85 years (+/- 6.72). The lower/upper lip involvement ratio was 9, mainly with mixed clinical patterns (76.9%), generally including erosion and mild keratosis. In most cases, the lips were involved with other oral sites but displayed a better evolution of the lesions. The literature review showed 21 reports of LPL (35 patients, female/male ratio 0.4) with a mean (+/- SD) age of 45.35 years (+/- 16.19). CONCLUSIONS: In the literature, erosive (28.57%) lower lip lesions showed a clear predominance (lower/upper lip ratio 6.5). One case of malignant transformation was also reported. The prevalence of isolated LPL was clearly reported only in two studies, ranging from 0.51% to 8.9%. In our patients, lesions were mostly found at the inner border of the lower vermillion and presented a tendency for self-limitation, or to regression after treatment, like cutaneous lesions. The lip lesions were small and easy to overlook, and therefore the prevalence of these lesions may have been underestimated. PMID- 26992293 TI - Facial Psoriasis Log-based Area and Severity Index: A valid and reliable severity measurement method detecting improvement of facial psoriasis in clinical practice settings. AB - Facial psoriasis is often observed in moderate to severe degrees of psoriasis. While we previously demonstrated construct validity of the facial Psoriasis Log based Area and Severity Index (fPLASI) system for the cross-sectional evaluation of facial psoriasis, its reliability and accuracy to detect clinical improvement has not been confirmed yet. The aim of this study is to analyze whether the fPLASI properly represents the range of improvement for facial psoriasis compared with the existing facial Psoriasis Area and Severity Index (fPASI) after receiving systemic treatments in clinical practice settings. The changing severity of facial psoriasis for 118 patients was calculated by the scales of fPASI and fPLASI between two time points after systemic treatments. Then, percentage changes (DeltafPASI and DeltafPLASI) were analyzed from the perspective of both the Physician's Global Assessment of effectiveness (PGA) and patients' Subjective Global Assessment (SGA). As a result, the distribution of the fPASI was more heavily clustered around the low score range compared with the fPLASI at both first and second visits. Linear regression analysis between DeltafPASI and DeltafPLASI shows that the correlation coefficient was 0.94, and DeltafPLASI represented greater percentage changes than DeltafPASI. Remarkably, degrees of clinical improvement measured by the PGA matched better with DeltafPLASI, while DeltafPASI underestimated clinical improvements compared with DeltafPLASI from treatment-responding groups by the PGA and SGA. In conclusion, the fPLASI represented clinical improvement of facial psoriasis with more sensitivity and reliability compared with the fPASI. Therefore, the PLASI system would be a viable severity measurement method for facial psoriasis in clinical practice. PMID- 26992294 TI - Proteome profiling of the growth phases of Leishmania pifanoi promastigotes in axenic culture reveals differential abundance of immunostimulatory proteins. AB - Leishmaniasis is a term that encompasses a compendium of neglected tropical diseases caused by dimorphic and digenetic protozoan parasites from the genus Leishmania (Kinetoplastida: Trypanosomatidae). The clinical manifestations of neotropical cutaneous leishmaniasis (NCL) caused by Leishmania pifanoi and other species of the "Leishmania mexicana complex" mainly correspond to anergic diffuse cutaneous leishmaniasis (ADCL), which is the origin of considerable morbidity. Despite the outstanding advances in the characterization of the trypanosomatid genomes and proteomes, the biology of this species has been scarcely explored. However, the close relation of L. pifanoi to the sequenced species L. mexicana and others included in the "L. mexicana complex" allowed us to perform a two dimension electrophoresis (2DE) approach to the promastigote proteome at the differential expression level. Protein identifications were performed by matrix assisted laser desorption-ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF). This insight has revealed similarities and differences between L. pifanoi and other species responsible for cutaneous and visceral leishmaniasis. Interestingly, certain proteins that were previously described as immunostimulatory (elongation factor 1beta, trypanothione peroxidase, heat shock protein 70, enolase, GDP-forming succinyl-CoA and aldehyde dehydrogenase) are more abundant in the final growth stages of promastigotes (late-logarithmic and/or stationary phase) in the case of L. pifanoi. PMID- 26992296 TI - Morphological and ultrastructural aspects of Myxobolus niger n. sp. (Myxozoa) gill parasite of Corydoras melini (Siluriformes: Callichthyidae) from Brazilian Amazon. AB - Myxobolus niger n. sp. (Myxozoa) is described in the connective tissue of the serosa layer of the gill arch of Corydoras melini (Callichthyidae) captured from the Negro River, Amazonas State, Brazil. The prevalence of the parasite was 20% and the range intensity was 1-2 cysts per fish. The plasmodia were white and spherical to ellipsoidal, measuring 175 MUm in diameter and were surrounded by a well-defined capsule of host connective tissue, with distinct delicate and interlaced collagen fibers. The myxospores body was ellipsoidal in frontal view and biconvex in sutural view. Spore dimensions were 11.3 +/- 0.4 MUm in length, 6.8 +/- 0.2 MUm in width and 4.1 +/- 0.2 MUm in thickness. The valves were symmetrical and smooth. The two polar capsules were elongated as pyriform and equal in size, measure 5.0 +/- 0.3 MUm in length and 2.0 +/- 0.1 MUm in width. The polar capsule had six to seven polar filament turns. Some aberrant spores were round in shape and had three polar capsules. The sporoplasm was binucleated and contained moderated number of sporoplasmosomes. The development of the plasmodia was asynchronic, with mature and immature spores. The plasmodium had moderated pynocitic channels. There were no projections, no invaginations and no microvilli in the plasmodial wall. This study is the first description of Myxobolus species in the fish of the Callichthyidae family. PMID- 26992295 TI - Assessing the impact of a joint human-porcine intervention package for Taenia solium control: Results of a pilot study from northern Lao PDR. AB - Following confirmation that a remote village of approximately 300 inhabitants in northern Lao PDR was hyperendemic for the Neglected Tropical Disease Taenia solium, a pilot human-porcine therapeutic control intervention was implemented between October 2013 and November 2014. Mass drug administration with a three day albendazole 400mg protocol was offered to all eligible humans in October 2013 and March 2014. At these times, and again in October 2014, eligible village pigs received the anti-cysticercosis TSOL18 vaccination and an oral dose of oxfendazole anthelmintic at 30mg/kg, both repeated one month later. Community and individual human taeniasis prevalences were estimated via copro-antigen ELISA of volunteered human faecal samples prior to October 2013, and again in January 2015, in order to examine the short term impact of the intervention. PMID- 26992297 TI - Kdr mutations in Triatoma infestans from the Gran Chaco are distributed in two differentiated foci: Implications for pyrethroid resistance management. AB - Point mutations in the voltage-gated sodium channel, the primary target of pyrethroid insecticides, have been associated with the resistance in Triatoma infestans, an important vector of Chagas' disease. Hence, the sustainability of vector control programs requires the implementation of resistance management strategies. We determined the sensitivity of the molecular assays previously designed for early resistance detection to be used in pooled samples from a wide area of the endemic region, and validated them for their routine use in control campaigns for the monitoring of insecticide resistance in T. infestans. Consequently, we used these methods to examine the distribution of resistance associated mutations in the sodium channel gene in populations of T. infestans from the Argentinean and Bolivian Gran Chaco. The PASA and REA assays tested proved sensitive enough to detect kdr SNPs in pooled samples, indicating these assays are suitable for routine screening in insecticide resistance surveillance. Two geographically differentiated foci were detected in T. infestans populations from the Argentinean and Bolivian Gran Chaco, with populations on the Bolivian Argentinean border carrying L1014F mutation, and those from the Argentinean Chaco carrying L925I mutation. In all highly resistant populations analyzed, one of both kdr mutations was present, and toxicological assays determined that all pyrethroid resistant populations analyzed herein were sensitive to fenitrothion. The principal cause of pyrethroid resistance in T. infestans from the Gran Chaco ecoregion is kdr mutations in the sodium channel. Different levels of resistance occur in different populations carrying identical mutation, suggesting the existence of contributory mechanisms. PMID- 26992298 TI - DNA barcoding to identify species of phlebotomine sand fly (Diptera: Psychodidae) in the mixed leishmaniasis focus of the Colombian Caribbean. AB - Identification of the species of phlebotomine sand flies present in each focus of leishmaniasis is necessary to incriminate vectors and implement vector control strategies. Although the cytochrome oxidase I (COI) gene has been proposed as a barcode for the identification of animal species, less than 20% of New World phlebotomines have been characterized to date. In this study DNA barcoding was used to identify phlebotomine species of the mixed leishmaniasis focus in the Colombian Caribbean by means of three evolutionary models: Kimura's two parameter (K2P) nucleotide substitution model, that of (Tamura and Nei, 1993) (TN93) and proportional sequence divergence (p-distances). A 681bp sequence of the COI gene was obtained from 66 individuals belonging to 19 species of the genus Lutzomyia (Lu. abonnenci, Lu. atroclavata, Lu. bicolor, Lu. carpenteri, Lu. cayennensis cayennensis, Lu. dubitans, Lu. evansi, Lu. gomezi, Lu. gorbitzi, Lu. longipalpis, Lu. micropyga, Lu. migonei, Lu. panamensis, Lu. (Psathyromyia) sp., Lu. rangeliana, Lu. serrana, Lu. shannoni, Lu. trinidadensis and Lu. venezuelensis) and one of Brumptomyia (B. mesai). The genetic divergence values for TN93 among individuals of the same species fluctuated up to 3.2% (vs. 2.9% for K2P and 2.8% for p-distances), while the values between species ranged from 8.8-43.7% (vs. 6.8 19.6% for K2P and 6.6-17.4% for p-distances). A dendrogram constructed by means of the Neighbor-Joining method grouped phlebotomines into 20 clusters according to species, with bootstrap values of up to 100% in those with more than one individual. However, loss of the phylogenetic signal of the gene COI was observed at the supraspecific level as a consequence of substitutional saturation. In conclusion, irrespective of the evolutionary model selected, all phlebotomines were correctly assigned to species, showing 100% concordance with morphological identification. PMID- 26992299 TI - A preliminary study on epigenetic regulation of Acanthopanax senticosus in leukemia cell lines. AB - Conventional chemotherapy for leukemia inevitably causes systemic toxicity. Acanthopanax senticosus, a naturally occurring herb used in traditional Chinese medicine, has been found to be a multipotent bioflavonoid with great potential in the prevention and treatment of malignant diseases. However, the mechanism underlying the action of A. senticosus in epigenetic regulation is poorly understood. In the study described here, we focused on the efficacy of A. senticosus in inducing apoptosis of leukemia cells and a possible mechanism. By evaluating the inhibition ratio and morphologic changes, we found that A. senticosus can inhibit growth and induce apoptosis of human leukemia HL-60 and HL60/ADM cells in a dose- and time-dependent manner. Furthermore, A. senticosus induced Fas ligand (FasL) expression and blocked the cell cycle in S phase. In addition, A. senticosus exhibited a potential for inhibition of histone deacetylase (HADC), which contributes to histone acetylation. It possibly resulted in the promotion of the expression of FasL. It is suggested that A. senticosus could be recognized as a new HDAC inhibitor which was able to reactivate aberrantly silenced genes. We discuss the clinical aspects of using A. senticosus for treatment of leukemia. PMID- 26992300 TI - Angiotensin-(1-7) improves non-alcoholic steatohepatitis through an adiponectin independent mechanism. AB - AIM: Recent evidence suggests that angiotensin-(1-7) [Ang-(1-7)] could improve non-alcoholic steatohepatitis (NASH) through an adiponectin-dependent mechanism. This study aimed to investigate whether and how Ang-(1-7) influences NASH without adiponectin. METHODS: Adiponectin knockout mice were fed with a high fat diet (HFD) or normal chow for 6 months, and were subsequently infused with Ang-(1-7) or saline for 2 weeks. RESULTS: We found that HFD-fed mice showed obesity, hyperlipidemia, NASH, and significantly increased levels of serum Ang-(1-7). Chronic infusion of Ang-(1-7) could reduce body weight, absolute and relative liver weight, and serum levels of total cholesterol, triglyceride, and low density lipoprotein cholesterol in HFD-fed mice. In addition, Ang-(1-7) treatment could attenuate hepatocellular inflammation, steatosis, and ballooning with activation of the hepatic AMP-activated protein kinase signaling pathway in HFD fed knockout mice. CONCLUSIONS: These results showed the protective role of Ang (1-7) in the development of NASH through an adiponectin-independent mechanism, which may be partially attributed to the activation of hepatic AMP-activated protein kinase pathway. PMID- 26992302 TI - Safety and efficacy of ultrasound-accelerated catheter-directed lytic therapy in acute pulmonary embolism with and without hemodynamic instability. AB - OBJECTIVE: The objective of this study was to evaluate the safety and effectiveness of ultrasound-accelerated thrombolysis in acute pulmonary embolism. METHODS: A retrospective study of 45 patients was performed to evaluate treatment of acute pulmonary embolism at a single center from January 2011 to December 2013. All patients were diagnosed with computed tomography or ventilation perfusion scan and had hemodynamic instability (systolic blood pressure <100 mm Hg) or right-sided heart strain evidenced by right ventricular dilation, septal deviation, or hypokinesis by echocardiography or computed tomography. EkoSonic catheters (EKOS Corporation, Bothell, Wash) were placed into the affected pulmonary arteries, and recombinant tissue plasminogen activator was infused through the catheters at 0.5 to 1.0 mg/h per catheter. RESULTS: Hypotension (systolic blood pressure <100 mm Hg) was present in 12 patients, with 100% resolution by treatment completion. Tachycardia (heart rate >100 beats/minute) was present in 26 patients and resolved in 92% by treatment completion; the average heart rate for all patients decreased from 109 to 77 beats/minute during the treatment period. Direct pulmonary artery pressure measurement showed average decrease of 21.5 mm Hg, representing a 40.2% reduction. Postprocedure echocardiography demonstrated complete resolution of cardiac dysfunction in 64%. Patients received a total dose of 30.5 mg (range, 14-66 mg) recombinant tissue plasminogen activator during an infusion time of 14.2 hours (range, 8-21 hours). There were no deaths through 90 days of follow-up and no major periprocedural bleeding events. CONCLUSIONS: This retrospective study demonstrates the safety and efficacy of current ultrasound-accelerated thrombolysis methods to treat acute pulmonary embolism. PMID- 26992303 TI - Durability of treatment effect with polidocanol endovenous microfoam on varicose vein symptoms and appearance (VANISH-2). AB - OBJECTIVE: The objectives of this study were to assess the durability of response to treatment with polidocanol endovenous microfoam (Varithena; Provensis Ltd, a BTG International group company) and to assess the long-term safety of the study patients. METHODS: This report presents efficacy and safety data from the day after visit 5/week 8 (the primary end point of the study) through the 1-year study visit. As the approved dose concentration is 1%, this analysis focuses on those patients who were randomized to polidocanol endovenous microfoam 1% at study visit 2. Because the objective of the 1-year analysis was to assess the durability of response to treatment with polidocanol endovenous microfoam 1%, the 1-year efficacy analyses based on the efficacy population included all patients who were randomized and received at least one treatment with polidocanol endovenous microfoam 1%. Efficacy end points in the Polidocanol Endovenous Microfoam Versus Vehicle for the Treatment of Saphenofemoral Junction Incompetence (VANISH-2) trial were evaluated at 1 year (n = 221; 96% of those completed the primary end-point measurement at week 8) and included the following: Varicose Vein Symptoms Questionnaire (VVSymQ, Provensis Ltd) score, an assessment of symptoms by patients using electronic daily diaries; Independent Photography Review: Visible Varicose Veins (IPR-V(3)) and Patient Self-assessment of Visible Varicose Veins (PA-V(3)) scores, the assessment of appearance by an Independent Physician Review panel and by patient self-assessment, respectively; duplex ultrasound response (physiologic response to treatment); Venous Clinical Severity Score (disease severity); and Venous Insufficiency Epidemiological and Economic Study on Quality of Life (VEINES-QOL) score (quality of life). RESULTS: Of the 230 patients who completed visit 5/week 8, 56 received polidocanol endovenous microfoam 1% at visit 2/week 0 and were subsequently assessed for efficacy at visit 5/week 8 and visit 10/1 year (one patient of the 57 who completed visit 5/week 8 received a nonpolidocanol endovenous microfoam intervention and was not included in the assessment). At 1 year after the first study treatment, patients treated with polidocanol endovenous microfoam demonstrated consistent, durable, and clinically meaningful improvements in symptoms, as measured by reductions in mean VVSymQ score; appearance, as measured by IPR-V(3) (clinician assessment) and PA-V(3) (patient self-assessment) scores; disease severity, as measured by the Venous Clinical Severity Score; and quality of life, as measured by the VEINES-QOL score. At 1 year, there were no new venous thrombus adverse events (VTAEs) and no clinically important sequelae in patients who had a VTAE in the study. In addition, there were no serious adverse events that were determined by the investigator to be related to the study drug. No new safety signals were identified. In patients who previously had a VTAE, none had a recurrence of thrombus or evidence of post-thrombotic syndrome at 1 year. CONCLUSIONS: Treatment with polidocanol endovenous microfoam 1% led to durable, clinically meaningful, and ongoing improvements at 1 year in varicose vein symptoms and appearance. Serious adverse events were those expected during long term follow-up of the population of patients studied and were unrelated to treatment. PMID- 26992301 TI - A RIETE registry analysis of recurrent thromboembolism and hemorrhage in patients with catheter-related thrombosis. AB - BACKGROUND: Few studies have investigated the treatment and the outcomes of patients with catheter-related thrombosis (CRT). METHODS: The RIETE registry (Registro Informatizado de Enfermedad TromboEmbolica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of consecutive patients with objectively confirmed venous thromboembolism (VTE). We analyzed the characteristics, treatment, and outcomes of patients with CRT. RESULTS: Of 558 patients with CRT, 45 (8%) presented with a pulmonary embolism (PE) concomitantly. More patients had central line-associated thrombosis compared with port systems, but catheter type did not influence the risk of presenting with a PE. Patients with only CRT were more often prescribed low-molecular-weight heparin for the duration of their anticoagulant treatment compared with patients presenting with concomitant PE. VTE recurrences and major bleeding events occurred frequently during treatment with anticoagulation (7 per 100 patient years and 8.9 per 100 patient years, respectively). The rates of fatal PE recurrences (1.85 per 100 patient-years) and fatal bleeding (2.32 per 100 patient years) were similar. Patients with an additional transient risk factor for VTE had the lowest risk for VTE recurrences (odds ratio [OR], 0.07; 90% confidence interval [CI], 0.01-0.45) compared with patients with CRT and no additional transient risk factors. PE at presentation increased the risk of recurrent thrombosis by 2.4 times. Renal insufficiency was also an independent predictor of recurrent thrombosis (OR, 3.93; 90% CI, 2.0-7.7). The odds of recurrent thrombosis was decreased by 77% in patients who received anticoagulation therapy for >90 days compared with patients with a shorter treatment (OR, 0.23; 90% CI, 0.1-0.56). CONCLUSIONS: Concomitant PE occurs less frequently in CRT than lower extremity deep venous thrombosis, but it is associated with a worse outcome. CRT occurs in high-risk patients, and duration of anticoagulation must be predicated on balancing these risks. PMID- 26992304 TI - A longitudinal single-center cohort study on the prevalence and risk of accessory saphenous vein reflux after radiofrequency segmental thermal ablation of great saphenous veins. AB - OBJECTIVE: Endothermal ablation has become a commonly used technology for occlusion of refluxing great saphenous veins (GSVs). However, the risk for primarily untreated accessory saphenous veins (ASVs) to develop reflux during follow-up has not yet been defined. Here, the prevalence and risk of ASV reflux is explored. METHODS: During a prospective multicenter cohort study on radiofrequency segmental thermal ablation of refluxing GSVs, the presence and reflux status of ASVs were monitored in 93 legs in a single center. Control examinations were performed after 1 week and at 12, 24, 36, and 48 months. Life table and multiple regression analyses were used to describe frequency and risk factors for presence of reflux in untreated ASVs. RESULTS: Of 93 legs, 82 (88%) were available for 4-year follow-up. At baseline, 43 legs (46%) had an anterior ASV detectable by duplex ultrasound, with only two legs (2%) presenting with reflux. During 4 years of follow-up, according to life-table analysis, the proportion of legs with a detectable anterior ASV increased to 71% (n = 65); 32% of all legs and 55% of legs with a detectable anterior ASV exhibited refluxing anterior ASVs. Remarkably, in 35% of all legs with an anterior ASV, this reflux presented as a source of axial reflux, suggesting hemodynamic relevance. Posterior ASVs were detected in only 10 legs during 4-year follow-up, exhibiting reflux in only two cases. CONCLUSIONS: Whereas posterior ASVs were meaningless, refluxing anterior ASVs occurred in a significant proportion of legs after thermal ablation of GSVs. Whether nonrefluxing anterior ASVs should be treated at the time of GSV ablation needs further examination. PMID- 26992305 TI - Management of perforator vein aneurysms in the lower extremities. AB - OBJECTIVE: Perforator vein aneurysms (PVAs) of the lower extremity have not been defined or reported. This study reports the clinical presentation of patients, the PVA characteristics, and the clinical outcome of their management. METHODS: Patients with signs and symptoms of chronic venous disease who had a PVA were included. Diagnosis of a PVA was made with duplex ultrasound. Normal perforator veins have a diameter of <3 mm. A PVA was defined as a diameter dilation of >9 mm, and it was always found below the deep fascia. The topography and morphology of the aneurysms were described in detail. All PVAs were treated with subfascial ligation with or without aneurysm excision. All patients were followed up for a minimum of 3 months with clinical examination and duplex ultrasound, and complications were noted. RESULTS: There were 21 aneurysms identified in 19 patients. Fourteen (73.7%) patients were female. The mean age at diagnosis was 49 years with a standard deviation of 9. Aneurysm size ranged from 9.8 to 22.2 mm, with a mean diameter of 15.7 mm and a standard deviation of 3.8. Seventeen aneurysms were fusiform, one was saccular, and one was multilobar. The perforators of the great saphenous vein distribution were most frequently involved, whereas only one involved deep vein disease. Few patients had symptoms, such as pressure and pain directly over the affected perforator. There was no association between the location and size of the PVA and the severity of chronic venous disease. Fourteen patients were treated surgically; five patients preferred conservative treatment with elastic compression stockings. Fourteen patients (73.7%) had ligation with (n = 9) or without (n = 5) excision of the aneurysm. All underwent concomitant phlebectomies, and eight of them also had ultrasound-guided foam sclerotherapy. Endovenous thermal ablation of saphenous veins was performed in seven patients, whereas two had ligation and stripping. There were four minor postoperative complications in four patients, all of which resolved within 6 weeks. The median follow-up was 21 months, ranging from 3 to 52 months. There were no recurrences of a PVA. Five patients preferred conservative treatment. The diameter changed from 0 to 13 mm during the follow-up, and the patients' symptoms remained the same or had mild worsening. CONCLUSIONS: PVAs are rare without causing significant symptoms locally. Diagnosis is made with duplex ultrasound because the affected vein is located below the deep fascia. As only one case in our series of 19 involved the deep veins, we believe that PVAs originate from superficial veins. The condition is relatively benign, and the treatment outcomes are very good with limited complications experienced. However, selective treatment of PVAs may not be needed for most of them as treatment of the superficial veins connecting with the PVA may be sufficient. PMID- 26992306 TI - Endovascular management of symptomatic gastrointestinal complications associated with retrievable inferior vena cava filters. AB - OBJECTIVE: With the increase in retrievable inferior vena cava (IVC) filter use, a higher than expected reported rate of pericaval tine penetration is observed. Symptomatic gastrointestinal (GI) complications associated with retrievable IVC filters have been documented; however, their management remains controversial. We describe a series of GI complications of retrievable IVC filters, detailing the spectrum of presenting symptoms and multiple treatment options, including the safety of endovascular retrieval. METHODS: A retrospective chart review was performed to describe the presentation, diagnosis, and treatment of patients with symptomatic GI complications associated with retrievable IVC filters from 2008 to 2014. RESULTS: Nine patients had symptomatic GI complications associated with a retrievable IVC filter (two G2 Recovery [Bard Peripheral Vascular, Tempe, Ariz], seven Celect [Cook Medical, Bloomington, Ind]; six women; age range, 17-81 years). All patients had small bowel perforation on computed tomography scan, four confirmed by esophagogastroduodenoscopy. Concomitant aortic and vertebral penetration occurred in seven and five patients, respectively. Patients presented with various abdominal complaints; one patient presented in acute sepsis. Two patients underwent laparotomy without complications. The remaining seven patients had attempted endovascular retrieval, six of which were successful. One patient's IVC filter was unable to be retrieved, and he was managed medically. Of the six patients who had successful endovascular retrieval, all had resolution of their symptoms with no complications, except for transient sepsis in a single patient who was not receiving periprocedural antibiotics. A follow-up computed tomography scan was performed 48 to 72 hours after endovascular retrieval and ruled out duodenal leak in all patients. Long-term follow-up demonstrated continued resolution of GI symptoms without further episodes of deep venous thrombosis or pulmonary embolism. CONCLUSIONS: GI complications of retrievable IVC filters are manifested with a wide spectrum of symptoms and frequent concomitant aortic and vertebral penetration. Endovascular retrieval can be safely used as a first-line therapy even in the setting of small bowel and aortic penetration. PMID- 26992307 TI - Venous angioplasty and stenting improve pelvic congestion syndrome caused by venous outflow obstruction. AB - OBJECTIVE: Pelvic congestion syndrome (PCS) is widely thought to be due to ovarian or internal iliac vein reflux. This report of a retrospective review of treatment of nonthrombotic common iliac vein (CIV) or inferior vena cava (IVC) obstruction with relief of symptoms demonstrates an often overlooked pathologic process. Stent placement is evaluated as an effective treatment of PCS due to venous obstruction even if observed left ovarian vein (OV) reflux is left untreated. METHODS: Records from two institutions were reviewed for patients with nonthrombotic venous outflow obstruction and symptoms of PCS severely affecting quality of life. The patients were evaluated with ultrasound, computed tomography (CT), and intravascular ultrasound before stent placement. From January 2008 through May 2013, 19 patients were treated with stents for severe venous outflow obstruction. Although seven patients also were found to have OV reflux, only one of these was treated with left OV coil occlusion. RESULTS: Whereas 10 of the 19 patients presented with a chief complaint of lower extremity pain, edema, or varicose veins, all patients described their pelvic symptoms as their dominant complaint. Ultrasound and CT suggested moderate to severe compression of the left CIV in 18 patients and a high-grade stenosis of the suprarenal IVC in one patient. Venography showed outflow obstruction with pelvic collaterals, and intravascular ultrasound confirmed focal severe stenosis of the involved vein. Follow-up of 1 to 59 months (median, 11 months) revealed complete resolution of pelvic pain in 15 of 19 patients and of dyspareunia in 14 of 17 sexually active patients. Of the 15 patients who experienced left lower extremity pain or edema before treatment, 13 experienced complete resolution after treatment. Imaging follow-up by ultrasound or CT showed 16 of the stents to be widely patent, with 3 minor asymptomatic stenoses. CONCLUSIONS: Nonthrombotic obstruction of the left CIV or IVC is an underappreciated cause of PCS. Venous angioplasty and stenting provide excellent short-term results for such patients, with resolution of chronic pelvic pain and dyspareunia. Venous obstruction should be considered and carefully evaluated in patients presenting with pelvic congestion, and treatment of obstruction alone may solve the patient's symptoms. PMID- 26992308 TI - Concurrent venography during first rib resection and scalenectomy for venous thoracic outlet syndrome is safe and efficient. AB - OBJECTIVE: Surgical treatment of acute axillosubclavian vein thrombosis from venous thoracic outlet syndrome (VTOS) traditionally involves first rib resection and scalenectomy (FRRS) followed by interval venography and balloon angioplasty. This approach can lead to an extended need for anticoagulation and a separate anesthesia session. We present outcomes for FRRS with concurrent venography. METHODS: Retrospective chart review was performed for consecutive patients undergoing FRRS with concurrent venography for VTOS from February 2007 to April 2014. Venography was performed immediately after FRRS with the arm in neutral and provocative positions. The primary outcomes of this study were primary and primary-assisted patency. Secondary outcomes included whether concurrent venography resulted in modification of the procedure, postoperative anticoagulation use, and postoperative complications. RESULTS: Thirty patients underwent first rib resection with venography with a mean follow-up time of 24.4 months. The mean age was 29.5 years (range, 17-52 years), and 17 (56.7%) were female. All were maintained on anticoagulation before the procedure. Concurrent venography resulted in modification of the procedure in 28 patients (93.3%). Of these, 27 patients (96.4%) underwent balloon angioplasty and two patients (7.1%) underwent further rib resection. Twenty patients (66.7%) were discharged after the procedure with no anticoagulation. For those receiving postoperative anticoagulation for persistent minor thrombus, median time for anticoagulation duration was 5.0 months (range, 0.8 and 16.7 months). Two patients (6.7%) had postoperative bleeding requiring thoracentesis or video-assisted thoracoscopic evacuation of hemothorax. One patient (3.3%) suffered rethrombosis and was successfully lysed open, resulting in a 2-year subclavian vein (SCV) primary patency of 96.7% and primary-assisted patency of 100%. No patients required reoperation for VTOS, and all reported improvements in symptoms. Three patients (10.0%) later underwent prophylactic first rib resection on the contralateral side for symptoms and SCV stenosis. CONCLUSIONS: FRRS with concurrent venography is a safe procedure for VTOS that allows effective intraoperative modification of the surgical plan, resulting in excellent patency of the SCV, early cessation of anticoagulation, and durable relief of symptoms. PMID- 26992309 TI - A study of increase in leg volume during complex physical therapy for leg lymphedema using subcutaneous tissue ultrasonography. AB - OBJECTIVE: The purpose of this study was to discuss the mode of increase in leg volume during complex physical therapy (CPT) for lymphedema using subcutaneous tissue ultrasonography. METHODS: Thirty-eight patients (51 legs) with secondary lymphedema who were treated by CPT for longer than 2 years (3.0 +/- 0.8 years) at our clinic were studied. The leg circumferences were measured at every visit. Subcutaneous tissue ultrasonography was performed at the initial and latest visits. RESULTS: The overall change in leg volume was -284 +/- 915 (range, -4588 to 1139) mL. Among them, the increase in leg volume was found in 18 legs; of those, 9 (1 in stage I, 7 in stage II, 1 in stage III) were adherent to hosiery use. In the legs whose average volume was decreased (group A, n = 33; mean, -821 [-4588 to -19] mL), the circumference had decreased in all the leg levels. However, in the legs whose average volumes had increased (group B, n = 18; mean, +449 [18-1139] mL), the circumference had increased in the thigh but remained unchanged or even decreased in the lower leg. In group B, subcutaneous thickness (SCT), subcutaneous echogenicity (SEG), and subcutaneous echo-free space (SEFS), assessed by ultrasonography, were found to have increased particularly in the lower medial thigh compared with those in group A (SCT change: group A, -1.5 +/- 5.9 cm vs group B, 3.7 +/- 5.4 cm [P < .05]; SEG grade change: group A, -0.3 +/- 0.7 vs group B, 0.3 +/- 0.7 [P < .05]; SEFS grade change: group A, -0.1 +/- 0.7 vs group B, 0.4 +/- 0.6 [P < .05]), whereas these remained unchanged or even decreased in the lower leg. CONCLUSIONS: Increase in leg volume during CPT might not be caused simply by noncompliance to hosiery use and seemed closely related to the increase in thigh circumferences, particularly the lower thigh, in which SCT, SEG, and SEFS were increased. PMID- 26992310 TI - Growth and remodeling of canine common iliac vein in response to venous reflux and hypertension. AB - OBJECTIVE: The passive properties of the venous wall are important for the compliance function of the venous system. The objective of this study was to quantify the passive biomechanical response and structural growth and remodeling of veins subjected to chronic venous reflux and hypertension. METHODS: To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured in a canine model by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound was used to investigate the passive biomechanical response of both control common iliac veins (n = 9 dogs) and common iliac veins subjected to 8 weeks of venous reflux and hypertension (n = 9 dogs). The changes in vein wall thickness and constituent composition were quantified by multiphoton microscopy and histologic evaluation. RESULTS: Biomechanical results indicate that the veins became less compliant when exposed to 8 weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be associated with a significant increase in wall thickness (P < .05) and collagen-to-elastin ratio (P < .05). After 8 weeks of chronic reflux and hypertension, the circumferential vein wall stress was significantly reduced (P < .05) because of wall thickening, although it was not restored to control levels. CONCLUSIONS: The growth and remodeling of the venous wall reduces the wall stress, but the stress remains higher than at baseline at 8 weeks. The compliance of the veins also decreases because of the increase in wall thickness and remodeling of the microstructure of the venous wall. These findings provide insight into potential adaptations of the venous system in reflux and hypertension. PMID- 26992311 TI - The effects of environmental and compositional manipulations on the longevity of Tessari-made foam for sclerotherapy. AB - BACKGROUND: Tessari-made foam sclerotherapy is performed around the world in a variety of clinics differing in methods, equipment, temperatures, and altitudes. We investigated how the following factors affected the foam's longevity: silicone vs nonsilicone syringes, volume of foam made, ratio of gas to sclerosant, use of air vs 50:50 mixture of carbon dioxide and oxygen, temperature, altitude, and 10 consecutive reuses of the syringes. METHODS: Sclerosant foam was made by the Tessari double-syringe technique. To calculate the longevity, the time was taken for half of the original volume of sclerosant to settle. Half-lives were compared with use of silicone and silicone-free syringes to make the foam. We investigated how the volume (5 mL vs 2 mL) and different ratios affected the foam by observing the half-life of 4:1, 3.5:1, and 3:1 ratios of gas to sclerosant. Air and a 50:50 mixture of carbon dioxide and oxygen were both used as the gas in changing the ratio and volume to see which produced better foam. These experiments were conducted at room (23.9 degrees C) and refrigerator (3 degrees C) temperatures with a constant pressure. The different ratio, volume, and silicone vs nonsilicone syringe experiments were all repeated at 9314, 7460, 4575, and 2326 feet above sea level in addition to the baseline experiment, which took place at 236 feet above sea level. To test how consecutive uses of syringes affected the foam, we made consecutive batches of foam reusing each pair of syringes 10 times; this was repeated five times with silicone syringes and twice with nonsilicone syringes. RESULTS: Switching to nonsilicone syringes can increase longevity by 70%. A larger volume of foam and a 3:1 ratio produced longer half-lives at all temperatures and altitudes. The lower (3 degrees C) temperature increased the longevity of foam in all instances, as did the use of air. A high altitude (low pressure) had a detrimental effect on the foam's longevity. Ten consecutive syringe uses had no significant impact on the foam's half-life (silicone syringe mean between first five and last five uses, P = .95). CONCLUSIONS: The optimum conditions for making foam are nonsilicone syringes, larger volumes, a 3:1 air to sclerosant ratio, and low temperatures. Silicone syringes can be reused until friction becomes a burden. Temperature has a bigger effect than altitude on longevity of the foam. Making foam in larger volumes would allow the foam to last longer. To compensate for high altitudes (low pressures), decreasing the temperature will increase the foam's longevity. PMID- 26992312 TI - Hypersensitivity to nickel in a patient treated with coil embolization for pelvic congestion syndrome. AB - A 34-year-old woman had persistent symptoms of pelvic venous congestion syndrome and developed new symptoms of a systemic allergic reaction after coil embolization of both ovarian and internal iliac veins. Patch testing revealed hypersensitivity to nickel and palladium, both components of the coils used. After surgical removal of the coils and hysterectomy with salpingo-oophorectomy, all her symptoms resolved. PMID- 26992313 TI - External iliac vein aneurysm as a cause of paradoxical embolism. AB - Iliac vein aneurysms are rare, even among venous aneurysms. We report the first case of an external iliac vein aneurysm presenting with paradoxical embolism to bilateral lower extremities. Workup after embolectomy demonstrated a patent foramen ovale along with the aneurysm and an inferior vena cava obstruction, which was treated with balloon angioplasty and ultimately stenting. The patient then underwent interval lateral aneurysmectomy. At 4-year follow-up, she is free of recurrence. PMID- 26992314 TI - Collateral venous drainage of solitary functioning left kidney with occluded renal vein following juxtarenal aortic aneurysm repair. PMID- 26992315 TI - Duplex imaging of residual venous obstruction to guide duration of therapy for lower extremity deep venous thrombosis. AB - BACKGROUND: Clinical trials have shown that the presence of ultrasound-identified residual venous obstruction (RVO) on follow-up scanning may be associated with an elevated risk for recurrence, thus providing a potential tool to help determine the optimal duration of anticoagulant therapy. We performed a systematic review to evaluate the clinical utility of post-treatment duplex imaging in predicting venous thromboembolism (VTE) recurrence and in adjusting duration of anticoagulation. METHODS: The Ovid MEDLINE Database, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were queried for the terms residual thrombus or obstruction, duration of therapy, deep vein thrombosis, deep venous thrombosis, DVT, venous thromboembolism, VTE, antithrombotic therapy, and anticoagulation, and 228 studies were selected for review. Six studies determined the rate of VTE recurrence on the basis of the presence or absence of RVO. RESULTS: Findings on venous ultrasound scans frequently remained abnormal in 38% to 80% of patients, despite at least 3 months of therapeutic anticoagulation. In evaluating for VTE recurrence, the definition of RVO varied widely in the literature. Some studies have shown an association between RVO and VTE recurrence, whereas other studies have not. Overall, the presence of RVO is a mild risk factor for recurrence (odds ratio, 1.3-2.0), but only when surveillance imaging is performed soon after the index deep venous thrombosis (3 months). CONCLUSIONS: RVO is a mild risk factor for VTE recurrence. The presence or absence of ultrasound-identified RVO has a limited role in guiding the duration of therapeutic anticoagulation. Further research is needed to evaluate its utility relative to other known risk factors for VTE recurrence. PMID- 26992316 TI - An overview of the most commonly used venous quality of life and clinical outcome measurements. AB - BACKGROUND: Modern medicine should no longer rely solely on technical success to evaluate treatments. The treatment of venous disease has seen many new developments, insights, and treatment modalities. Combining clinical scores with quality of life (QoL) outcome measurements is becoming the new norm for evaluation of treatments. Many different outcome assessment instruments are currently available, indicating a lack of consensus. METHODS: We set out to find the most reliable and comprehensive scoring instrument for clinical and QoL measurement in venous disease. In this review, we focus on the eight most widely used instruments. For clinical assessment, these are the Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification, Villalta scale, and Venous Clinical Severity Score (VCSS); for generic QoL, the 36-Item Short Form Health Survey (SF-36) and EQ-5D questionnaires; and for disease-specific QoL, the Aberdeen Varicose Vein Questionnaire (AVVQ), Chronic Venous Insufficiency Questionnaire (CIVIQ), and VEnous INsufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) questionnaire. Each instrument is reviewed. CONCLUSIONS: For the accurate evaluation of treatment outcomes, socioeconomic, QoL, and clinical aspects must be assessed. None of the available disease-specific instruments is suited to use in uniform outcome measurement for the whole spectrum of venous disease. A new combined QoL and clinical instrument is needed to validly assess and compare the outcomes of venous treatments. The VEINES-QOL/Sym is currently the most valid instrument to assess disease-specific QoL. PMID- 26992317 TI - Current management of isolated soleal and gastrocnemius vein thrombosis. AB - Thrombi of the soleal and gastrocnemius veins of the leg remain incompletely characterized in terms of the appropriate treatment algorithm to follow. Although they are anatomically located below the level of the fascia, making them "deep" vein thrombi, their natural history is unclear with respect to propagation and embolization. Varying treatment suggestions have been proposed, from full-dose anticoagulation to "watchful waiting" with repeated duplex examination, with none rising to the level of accepted scientific evidence. Herein, we present the current literature citing the differing opinions and data that have confused the subject. PMID- 26992318 TI - Reply. PMID- 26992319 TI - Regarding "Tumescent technique without epinephrine for endovenous laser therapy and serum lidocaine concentration". PMID- 26992323 TI - Physiotherapy management of lung cancer. PMID- 26992324 TI - National survey on specimen acceptability for complete blood count testing of clinical laboratories in China. PMID- 26992325 TI - Functional cellular analyses reveal energy metabolism defect and mitochondrial DNA depletion in a case of mitochondrial aconitase deficiency. AB - Defects in the tricarboxylic acid cycle (TCA) are associated with a spectrum of neurological phenotypes that are often difficult to diagnose and manage. Whole exome sequencing (WES) led to a rapid expansion of diagnostic capabilities in such disorders and facilitated a better understanding of disease pathogenesis, although functional characterization remains a bottleneck to the interpretation of potential pathological variants. We report a 2-year-old boy of Afro-Caribbean ancestry, who presented with neuromuscular symptoms without significant abnormalities on routine diagnostic evaluation. WES revealed compound heterozygous missense variants of uncertain significance in mitochondrial aconitase (ACO2), which encodes the TCA enzyme ACO2. Pathogenic variants in ACO2 have been described in a handful of families as the cause of infantile cerebellar retinal degeneration syndrome. Using biochemical and cellular assays in patient fibroblasts, we found that ACO2 expression was quantitatively normal, but ACO2 enzyme activity was <20% of that observed in control cells. We also observed a deficiency in cellular respiration and, for the first time, demonstrate evidence of mitochondrial DNA depletion and altered expression of some TCA components and electron transport chain subunits. The observed cellular defects were completely restored with ACO2 gene rescue. Our findings demonstrate the pathogenicity of two VUS in ACO2, provide novel mechanistic insights to TCA disturbances in ACO2 deficiency, and implicate mitochondrial DNA depletion in the pathogenesis of this recently described disorder. PMID- 26992326 TI - Varied autopsy findings in five treated patients with Gaucher disease and parkinsonism include the absence of Gaucher cells. AB - Enzyme replacement therapy is standard of care for patients with Gaucher disease, as it significantly improves skeletal, visceral, and hematological symptoms. Few pathological studies have documented the extent of pathological findings in treated patients. Autopsy findings in five treated patients, who ultimately developed parkinsonism, ranged from the complete absence of Gaucher pathology to extensive involvement of multiple tissues, without correlation to age, genotype, spleen status, or dose/duration of therapy. Additional autopsies may elucidate modifiers and biomarkers contributing to disease burden and response to therapy. PMID- 26992327 TI - Effects of metal contamination in situ on osmoregulation and oxygen consumption in the mudflat fiddler crab Uca rapax (Ocypodidae, Brachyura). AB - The contamination of estuaries by metals can impose additional stresses on estuarine species, which may exhibit a limited capability to adjust their regulatory processes and maintain physiological homeostasis. The mudflat fiddler crab Uca rapax is a typical estuarine crab, abundant in both pristine and contaminated areas along the Atlantic coast of Brazil. This study evaluates osmotic and ionic regulatory ability and gill Na(+)/K(+)-ATPase activity in different salinities (<0.5, 25 and 600/00 S) and oxygen consumption rates at different temperatures (15, 25 and 35 degrees C) in U. rapax collected from localities along the coast of Sao Paulo State showing different histories of metal contamination (most contaminated Ilha Diana, Santos>Rio Itapanhau, Bertioga>Picinguaba, Ubatuba [pristine reference site]). Our findings show that the contamination of U. rapax by metals in situ leads to bioaccumulation and induces biochemical and physiological changes compared to crabs from the pristine locality. U. rapax from the contaminated sites exhibit stronger hyper- and hypo osmotic regulatory abilities and show greater gill Na(+)/K(+)-ATPase activities than crabs from the pristine site, revealing that the underlying biochemical machinery can maintain systemic physiological processes functioning well. However, oxygen consumption, particularly at elevated temperatures, decreases in crabs showing high bioaccumulation titers but increases in crabs with low/moderate bioaccumulation levels. These data show that U. rapax chronically contaminated in situ exhibits compensatory biochemical and physiological adjustments, and reveal the importance of studies on organisms exposed to metals in situ, particularly estuarine invertebrates subject to frequent changes in natural environmental parameters like salinity and temperature. PMID- 26992328 TI - Paradoxical effects of temperature and solar irradiance on the photodegradation state of killed phytoplankton. AB - The aim of this paper was to study the effects of temperature and irradiance on the photodegradation state of killed phytoplankton cells. For this purpose, killed cells of the diatom Chaetoceros neogracilis RCC2022 were irradiated (photosynthetically active radiation) at 36 and 446 J . s(-1) . m(-2) (for the same cumulative dose of irradiation energy) and at two temperatures (7 degrees C and 17 degrees C). Analyses of specific lipid tracers (fatty acids and sterols) revealed that low temperatures and irradiances increased photooxidative damages of monounsaturated lipids (i.e., palmitoleic acid, cholesterol and campesterol). The high efficiency of type II photosensitized degradation processes was attributed to: (i) the relative preservation of the sensitizer (chlorophyll) at low irradiances allowing a longer production of singlet oxygen and (ii) the slow diffusion rate of singlet oxygen through membranes at low temperatures inducing more damages. Conversely, high temperatures and irradiances induced (i) a rapid degradation of the photosensitizer and a loss of singlet oxygen by diffusion outside the membranes (limiting type II photosensitized oxidation), and (ii) intense autoxidation processes degrading unsaturated cell lipids and oxidation products used as photodegradation tracers. Our results may explain the paradoxical relationship observed in situ between latitude and photodegradation state of phytoplankton cells. PMID- 26992330 TI - [Pleurisy induced by atorvastatin]. AB - INTRODUCTION: Whereas numerous case reports have described statin-induced lung injuries, statin-induced pleural effusions are uncommon. CASE REPORT: An 84-year old man presented with bilateral pleural effusions two years after starting treatment with atorvastatin. No other cause of pleural effusion was found and all symptoms and radiological signs resolved rapidly after discontinuation of the drug. Furthermore, an accidental reintroduction of the treatment resulted in recurrence of the same clinical picture, reinforcing the hypothesis that atorvastatin was responsible for this pleural effusion. CONCLUSION: Pleuropulmonary manifestations in a patient treated with atorvastatin should rapidly evoke an iatrogenic origin and the discontinuation of the drug should be discussed. PMID- 26992329 TI - Multiplex determination of serological signatures in the sera of colorectal cancer patients using hydrogel biochips. AB - Colorectal cancer (CRC) is the third most common malignancy in industrialized countries. Despite the advances in diagnostics and development of new drugs, the 5-year survival remains only 60-65%. Our approach to early diagnostics of CRC is based on the determination of serological signatures with an array of hemispherical hydrogel cells containing immobilized proteins and oligosaccharides (glycochip). The compounds immobilized on the glycochip include tumor-associated glycans (SiaTn, Tn, TF, Le(C) , Le(Y) , SiaLe(A) , and Manbeta1-4GlcNAcbeta) and antibodies against human immunoglobulins IgG, IgA, and IgM. The glycochip detects antibodies against tumor-associated glycans in patients' sera. The simultaneous measurement of the levels of immunoglobulins enhances the diagnostic impact of the signatures. In this work, we found previously unreported increase in antibodies against oligosaccharide Manbeta1-4GlcNAcbeta in patients with CRC. In parallel with these experiments, we determined the levels of oncomarkers carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA 125, CA 15-3, human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) using another gel-based biochip with immobilized antibodies (oncochip) developed earlier in our laboratory. In total, 69 samples from healthy donors, 33 from patients with colorectal carcinoma, and 27 from patients with inflammatory bowel diseases were studied. The use of combined signatures of antiglycan antibodies and oncomarkers provides much better predictive value than the conventional measurement of oncomarkers CEA and CA 19-9. Positive predictive value of CRC diagnoses using together glycochip and oncochip reached 95% with the sensitivity and specificity 88% and 98%, respectively. Thus, the combination of antibody profiling with detection of conventional oncomarkers proved to be a promising tool in diagnostics of CRC. PMID- 26992331 TI - Reliability of eye lens dosimetry in workers of a positron emission tomography radiopharmaceutical production facility. AB - A new regulatory statement was issued concerning the eye lens radiation protection of persons in planned exposures. A debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to establish the individual monitoring procedure with the EYE-DTM holder and a MCP-N LiF:Mg,Cu,P thermoluminescent chip detector for measuring the personal dose equivalent Hp(3) in workers of a Positron Emission Tomography Radiopharmaceutical Production Facility. PMID- 26992332 TI - Upper body exercise increases lower extremity venous blood flow in deep venous thrombosis. AB - OBJECTIVE: Sequential compression devices or ambulation prevent deep venous thrombosis (DVT) by enhancing venous blood flow in the lower extremity. However, compression therapy or ambulation may not be possible in patients with lower extremity surgery or trauma. We therefore determined whether upper body exercise increases venous blood flow in the lower extremities as a potential means for preventing DVT. METHODS: We determined blood volume flow and velocity responses in the common femoral veins to low-intensity (5 W, 75 rpm) upper body cycle ergometry in healthy individuals. Six protocols of single and intermittent bouts of exercise were tested. Upon determination of the most efficacious protocol in these participants, we verified the effects of upper body exercise in patients with acute DVT. Measurements were made before, during, and after exercise using duplex ultrasound imaging. RESULTS: The study enrolled 15 healthy volunteers (10 men, 5 women; aged 20-40 years) with no history of DVT and 10 patients (aged 31 86 years) with acute DVT. In healthy participants, a single 30-second bout of upper body exercise increased volume flow up to 39% for up to 10 minutes after exercise (P < .05). A single 3-minute bout increased flow to a lesser extent (23% increase; P = .05) for nearly 5 minutes, but a single 1-minute bout did not increase flow. An intermittent protocol of three 30-second bouts of exercise resulted in an increase of 34% to 57% in venous flow (P < .05) for an average increase of 179 +/- 53 mL/min. Intermittent 1-minute bouts of exercise tended to increase flow 10% to 40% (P = .06-.08) for an average increase of 149 +/- 64 mL/min. Intermittent 3-minute bouts of exercise increased flow 21% to 45% (P < .05) for an average increase of 120 +/- 42 mL/min. In patients with acute DVT, the intermittent 30-second upper body exercise protocol increased venous blood flow by 45% to 83% (P < .05) for an average increase of 250 +/- 63 mL/min, an effect lasting >13 minutes. CONCLUSIONS: We report the novel finding that upper body exercise increases lower extremity venous blood flow in healthy volunteers and in acute DVT patients. Three intermittent 30-second bouts of low-intensity upper body exercise elicited the highest response for the least amount of effort and may represent an alternative or adjunct for prophylaxis of DVT in patients with restricted ambulation. PMID- 26992333 TI - On the existence of helical flow in veins of the lower extremities. AB - PURPOSE: Helical flow has been shown to be present in the heart and arteries, but its existence in veins has not been demonstrated before. This study aimed to investigate if helical flow is present in the venous system and if the venous valves contribute to development of this flow pattern. METHODS: Color and spectral Doppler were used to calculate the true velocity vectors at five cross sectional planes of the femoral and common femoral veins in 10 healthy individuals and eight patients with chronic venous disease. RESULTS: This study demonstrated that helical flow is a normal finding in the segments of veins that are in close proximity and downstream from a venous valve and a venous junction. This flow pattern is more prevalent when the calf muscle pump is active. Incompetence of the proximal great saphenous vein affects the outflow pattern, so that the helical flow is no longer present and is replaced by disorganized turbulent flow. CONCLUSIONS: These findings suggest that helical flow is detectable, may have a physiological role in venous circulation, and the absence of it may be a feature of venous disease. PMID- 26992334 TI - Obstructive sleep apnea is associated with an increased risk of venous thromboembolism. AB - OBJECTIVE: This study aimed to investigate the risk for venous thromboembolism (VTE) among patients with obstructive sleep apnea (OSA) during the first 5 years following a diagnosis of OSA, compared with patients without OSA during the same period. METHODS: This study was a matched-cohort study in Taiwan that included 1424 study subjects with OSA and 14,240 randomly selected comparison subjects. We identified subjects who subsequently received a diagnosis of VTE within the first 5 years following their index date. Stratified Cox proportional hazards regressions were performed to compare the 5-year VTE-free survival rates between the study cohort and comparison cohort. RESULTS: The incidence of VTE was 2.67 (95% confidence interval [CI], 1.69-4.70) and 0.96 (95% CI, 0.75-1.20) for subjects with and without OSA, respectively. Stratified Cox proportional hazards regressions revealed that the hazard ratio for VTE among subjects with OSA was 2.07 (95% CI, 1.21-3.52) that of comparison subjects after adjusting for sociodemographic characteristics, cancer, inflammatory bowel disease, heart failure, hypertension, diabetes, coronary heart disease, hyperlipidemia, renal disease, obesity, whether or not a subject was hospitalized, whether or not a subject had suffered a fracture within 1 year prior to the index date, and censoring those who died during the 5-year follow-up period. We further found that the adjusted hazard ratio of deep vein thrombosis among OSA patients was 1.88 (95% CI, 1.08-3.29) that of comparison subjects. CONCLUSIONS: Our results suggest that there is an increased risk of deep vein thrombosis among OSA patients during the first 5 years following their diagnosis. PMID- 26992335 TI - Minimally invasive treatment of chronic iliofemoral venous occlusive disease. AB - BACKGROUND: As one of the primary etiologies of the post-thrombotic syndrome, chronic venous occlusion is a huge burden on patient quality of life and medical costs. In this study, we evaluate the short-term and midterm results of endovenous recanalization by angioplasty and stenting in chronic iliofemoral deep venous occlusions. METHODS: This is a retrospective observational study set in a tertiary medical referral center. Patients with venous claudication or C4-6 venous disease combined with duplex and magnetic resonance-confirmed iliofemoral or caval occlusion were included. Patients with recent deep vein thrombosis (<1 year) were excluded. The intervention was endovascular deep venous recanalization, followed by angioplasty and stenting. Safety and feasibility were clinically evaluated during the procedure and during follow-up. Reocclusions and other treatment failures were evaluated during a maximum follow-up of 31 months by ultrasound imaging and venography. RESULTS: Seventy-five procedures were performed in 63 patients (average age, 44 years; range, 18-75 years), of whom 86% had a history of deep venous thrombosis. The mean time between the initial deep venous thrombosis and treatment with PTA and stenting was 12 years (maximum, 31 years). May-Thurner syndrome was present in 57%. Forty-two procedures were performed in the left, six in the right, and 11 in both lower extremities. The vena cava inferior was partially stented in 25 patients. An average of 2.6 stents (median, 2) were used per procedure. Primary patency was 74% after 1 year. Assisted primary and secondary patency rates were 81% and 96%, respectively, at 1 year. Secondary procedures included restenting, catheter-directed thrombolysis, endophlebectomy of the common femoral vein, and creation of an arteriovenous fistula. No clinically evident pulmonary emboli were noted. A bleeding complication occurred after six procedures and was deemed major in two. No patients died. Relief or significant improvement of symptoms of chronic venous occlusive disease was achieved in 81% of patients. CONCLUSIONS: Endovenous recanalization by angioplasty and stenting of chronically occluded iliofemoral vein segments is a safe and effective treatment with good short-term results, even when treatment takes place decades after the initial deep venous thrombosis. Most reocclusions can be adequately treated by a secondary procedure. PMID- 26992336 TI - Pretreatment elevated D-dimer levels without systemic inflammatory response are associated with thrombotic complications of thermal ablation of the great saphenous vein. AB - OBJECTIVE: To examine possible association of plasma levels of biomarkers of inflammation and hemostatic activation with the incidence of thrombotic complications after thermal ablation of the great saphenous vein (GSV). METHODS: This was a prospective cohort study of 120 patients with primary chronic venous disease and reflux limited to the GSV and its tributaries, who were to undergo treatment with radiofrequency ablation of the GSV. Plasma concentration of C reactive protein (high-sensitivity CRP) and D-dimer were measured immediately prior to the ablation procedure, and in 64 patients, at 20 to 36 hours, 1 week, and 1 month after the treatment. A complete bilateral duplex ultrasound scan was performed prior to treatment, within the first 36 hours and at 1 month after treatment. Incidence of thrombotic complications was based on findings of duplex ultrasound scans. RESULTS: Sixteen patients developed thrombotic complications. These included seven endovenous heat-induced thromboses, seven thromboses of untreated superficial veins, one thrombosis of the posterior tibial vein, and one gastrocnemius vein thrombosis. In two patients, endovenous heat-induced thromboses coincided with superficial phlebitis. Multivariate analysis showed that patients who had a combination of normal baseline levels of CRP and elevated levels of D-dimer were more than seven times more likely to develop thrombotic complications compared with all other patients (odds ratio, 7.3; 95% confidence interval, 2.2-23.9; P = .002). Both CRP and D-dimer levels significantly increased at 24 to 36 hours and returned to the baseline values at 1 month after the treatment. The D-dimer levels were significantly higher in patients with thrombotic complications at the baseline, 24 to 36 hours and 1 week after the treatment but became not statistically significant a month after the treatment. CONCLUSIONS: These findings suggest that preoperative activation of the hemostatic system plays an important role in the development of thrombotic complications after thermal ablation of the GSV and that such activation can be detected by commonly used clinical practice laboratory tests. PMID- 26992337 TI - Incidence, progression, and risk factors for endovenous heat-induced thrombosis after radiofrequency ablation. AB - OBJECTIVE: Endovenous radiofrequency ablation has become an accepted mode of treatment for superficial venous reflux. In this study, we evaluated the incidence of endovenous heat-induced thrombosis (EHIT), its progression, and risk factors that may contribute to its formation. METHODS: This was a prospective study of all patients who underwent radiofrequency ablation of the great saphenous vein (GSV), accessory GSV, and small saphenous vein (SSV) from March 1, 2010, to September 30, 2011, from 12 of our affiliated vein centers in a primary vein practice. Demographic data, CEAP classification, previous history of deep venous thrombosis (DVT), body mass index, vein diameter, reflux time, catheter tip position, EHIT progression, number of stab phlebectomies, and Venous Clinical Severity Score of patients with EHIT were analyzed. RESULTS: Of the 6707 treated limbs, 4906 (73%) had GSV, 145 (2%) had accessory GSV, and 1656 (25%) had SSV ablation. EHIT developed in 201 limbs of 194 patients for an overall incidence of 3%. A nonfatal pulmonary embolism occurred in two patients (0.03%). Patients who developed EHIT were slightly older than those without EHIT (median age, 59 vs 56 years). In patients with EHIT, 34.8% were men, but only 25% were men among those who had no EHIT (P = .002). GSV, accessory GSV, and SSV diameters were larger in EHIT patients (P < .001 for all). Reflux time and catheter tip distance from the saphenous junctions were similar in those with and without EHIT. EHIT resolution occurred in 2 to 4 weeks in most patients, but EHIT worsening occurred in nine (4.5%) that all resolved <=4 weeks. In the EHIT patients, 68% had multiple concomitant phlebectomies compared with 39.4% of those without EHIT (P < .0001). DVT history made no difference for EHIT development (P = .065). All but two class 1 and one class 2 EHIT patients were managed with observation and aspirin due to DVT history and physician concern. The Venous Clinical Severity Score was obtained only in the last 70 EHIT cases. The mean score was 5.92 preoperatively and improved to 2.08 at the 1-month follow-up. CONCLUSIONS: Large vein diameter, male sex, and multiple phlebectomies are risk factors for development of EHIT. We recommend that EHIT class 1 and 2 patients be managed with observation or antiplatelets, or both, but class 3 and 4 patients should be anticoagulated. PMID- 26992339 TI - Invited commentary. PMID- 26992338 TI - Endovenous management of venous leg ulcers. AB - BACKGROUND: Compression is the current "standard" in the treatment of venous leg ulcers, and corrective surgery is ancillary. The emergence of safe and effective minimally invasive corrective techniques prompts a reappraisal of this paradigm. METHODS: Among 192 consecutive limbs with venous leg ulcers, 189 were treated by (1) endovenous laser ablation (n = 30), (2) iliac vein stent placement (n = 89), or (3) both (n = 69). Residual deep reflux was not treated. No specialized wound care was used, and 38% of patients did not use stockings. Outcome measures were time to heal the ulcer and cumulative long-term healing. RESULTS: Sixty percent of the limbs were post-thrombotic. The median reflux segment score was 3 (range, 0-7). Thirty-seven percent had deep axial reflux. Median intravascular ultrasound detected stenosis was 70% (range, 0%-100%) in stented patients. Sensitivity of venography to iliac vein obstruction was 52%. Postprocedural mortality was 0%, and 2% had deep venous thrombosis (<30 days). By 14 weeks, 81% of the small ulcers approximately <=1 inch in diameter had healed. Larger ulcers were slower in healing (P < .001). Post-thrombotic etiology, presence of uncorrected deep reflux, demographic factors, or stocking use had no bearing on healing time. Long term cumulative healing at 5 years overall was 75%. Healing was better in nonthrombotic limbs compared with post-thrombotic limbs (87% vs 66% at 5 years; P < .02) but was similar among the various demographic subsets, procedures, and whether or not patients used compression. Quality-of-life measures improved significantly. Cumulative long-term healing was unaffected by residual axial reflux and was unrelated to hemodynamic severity (air plethysmography, ambulatory venous pressure). However, long-term ulcer healing was inferior in limbs with reflux segment score of >=3 (P < .03). Post-thrombotic limbs with a reflux score of >=3 had the lowest cumulative healing among cohorts, but even in this category, 60% of limbs had durable healing with very few recurrences. CONCLUSIONS: Most venous leg ulcers in this consecutive series achieved long-term healing with the described minimally invasive algorithm. Uncorrected residual reflux was not an impediment to ulcer healing. Ulcers sized <=1 inch required no specialized or prolonged wound care. Compression was not necessary to achieve or maintain healing after interventional correction. PMID- 26992340 TI - First human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence. AB - OBJECTIVE: The primary objective of this study was to assess the feasibility of an endovenous cyanoacrylate (CA) adhesive implant, delivered with a catheter based administration system engineered with a nonstick surface, for the treatment of incompetent great saphenous veins (GSVs). The primary safety end point was the rate of serious adverse events related to the procedure. The primary efficacy end point was vein occlusion during follow-up. Secondary end points included the rate of all adverse events and the change in Venous Clinical Severity Scores (VCSSs). METHODS: Thirty-eight incompetent GSVs in 38 symptomatic patients were treated by catheter deployment of CA under ultrasound guidance via a repetitive bolus injection algorithm. By protocol design, perivenous tumescent anesthesia and compression stockings were omitted. Duplex ultrasound imaging and clinical follow up were performed immediately after the procedure, at 48 hours, and 1, 3, 6, and 12 months. RESULTS: The mean total volume of endovenous CA delivered was 1.3 +/- 0.4 mL (range, 0.6-2.3 mL). Immediately after the procedure and at the 48-hour follow-up, the 38 patients (100%) demonstrated complete closure of the GSV. One complete and two partial recanalizations were observed during follow-up at 1, 3, and 6 months, respectively. Kaplan-Meier analysis yielded an occlusion rate of 92% at 12 months of follow-up. Side effects were generally mild and self-limited, most frequently, phlebitis in six patients (15.8%) requiring nonsteroidal anti inflammatory drugs for an average of 5.7 days. Eight patients (21.1%) showed thread-like thrombus extensions into the common femoral vein of a mean length of 12.6 mm (range, 3.5-35 mm), which resolved spontaneously without anticoagulation. VCSS improved in all patients from a mean of 6.1 +/- 2.7 at baseline to 1.5 +/- 1.4 at 12 months (P < .0001). Edema improved in 34 legs (89%) at the 48-hour follow-up. At the 12-month follow-up, and without additional adjunctive treatment, 18 legs (50%) were free from visible varicosities and an additional eight legs (25%) showed limited varicosities. CONCLUSIONS: The first human use of endovenous CA for closure of insufficient GSVs proved to be feasible, safe, and effective. Endovenous delivery of CA may prove to be an alternative for the correction of saphenous incompetence and may be used without tumescent anesthesia and medical compression stockings. PMID- 26992341 TI - Popliteal vein compression syndrome pathophysiology and correlation with popliteal compartment pressures. AB - OBJECTIVE: The link between obesity and popliteal vein compression syndrome (PVCS) has been documented, but the pathophysiological mechanism is unclear. The aim of this study is to understand the pathogenesis of PVCS by assessing popliteal compartment pressures (PCP). METHODS: Twenty-three limbs (15 patients) were included. Eleven limbs were ultrasonically diagnosed with PVCS and underwent popliteal vein decompression. The control group consisted of 12 limbs with functional popliteal artery entrapment. Perioperatively, PCP measurements were obtained. The body mass index (BMI) was calculated and the clinical symptoms were documented (CEAP). RESULTS: The median BMI for the PVCS group was 32 (range, 26 45.8) compared with 28 (range, 19-31) for the control group (P = .05). In PVCS, the popliteal vein internal diameter was 9.4 mm (range, 8.0-20.0 mm) upon knee flexion, compared with 0 mm (range, 0.0-0.1 mm) upon knee extension. Upon knee flexion, there was no difference in pressure (PVCS 10.0 [range, 4-20] vs control 11.5 [range, 3-22]; P = .95). Upon knee extension, the median PCP in the PVCS group was 53 cm H2O (range, 38-76 cm H2O) compared with 26 cm H2O (range, 17-43 cm H2O) in the control group (P < .001). CONCLUSIONS: PVCS is associated with high popliteal compartment pressures compared with controls. The pathophysiology of popliteal obstruction, in the absence of anatomical abnormalities, is related to an increase in popliteal compartment pressure while standing due an increase of the popliteal fat pad, related to high BMI. PMID- 26992342 TI - Prevalence of various congenital vascular malformations in patients with Klippel Trenaunay syndrome. AB - OBJECTIVE: Klippel-Trenaunay syndrome (KTS) is a condition defined by the association of three physical features: capillary malformation, varicosities, and hypertrophy of bony and soft tissues. However, KTS is characterized by congenital vascular malformations (CVMs) that are difficult to classify. Therefore, the present study was undertaken to analyze the various CVMs in patients with KTS. METHODS: Sixty-one patients with KTS were enrolled, and their CVMs were divided into predominantly venous defects, predominantly lymphatic defects, and mixed vascular defects using the Hamburg Classification. Capillary malformations were subdivided into port-wine stain, telangiectasia, and angiokeratoma. Truncular and extratruncular vascular malformations were detected using duplex ultrasound and magnetic resonance imaging. Reflux in the superficial and deep venous systems was also evaluated. RESULTS: Forty-five patients (74%) had predominantly venous defects, four (6%) had predominantly lymphatic defects, and 12 (20%) had mixed vascular defects. Capillary malformations were detected in 54 patients (89%), among which port-wine stain was the most predominant (40 patients, 66%), followed by telangiectasia (31 patients, 51%) and angiokeratoma (18 patients, 30%). Extratruncular venous malformations were detected in 47 patients (77%). In contrast, truncular venous malformations were found in 50 patients (82%). Among these, embryonic lateral marginal vein showed the highest occurrence, accounting for 53% (32 patients). However, reflux in this vein was detected in only nine patients (15%). Twelve patients (20%) had reflux in the great saphenous vein, and four (7%) had reflux in the small saphenous vein. Deep vein hypoplasia was found in seven patients (12%), and only five patients (8%) had deep vein aplasia. Extratruncular lymphatic malformations were found in 13 patients (21%) and truncular lymphatic malformations in 17 (28%). CONCLUSIONS: Patients with KTS have a variety of CVMs, but both extratruncular and truncular venous malformations continue to be targets for intervention. PMID- 26992343 TI - Indocyanine green lymphography is superior to lymphoscintigraphy in imaging diagnosis of secondary lymphedema of the lower limbs. AB - OBJECTIVE: Lymphedema is commonly viewed as difficult to treat, but lymphaticovenous anastomosis applied early after onset can be curative in some cases. Therefore, early diagnosis of cancer-related lymphedema is important. Lymphoscintigraphy is currently the most common method used for imaging diagnosis of lymphedema, but indocyanine green fluorescence lymphangiography (ICG lymphography) is also increasingly used for this purpose. The goal of this study was to compare the accuracy of these methods for diagnosis of lymphedema. METHODS: This was a prospective comparative study, conducted at a general hospital in Japan. The subjects were 29 consecutive patients (all female; age range, 32-79 years) with lymphedema (58 limbs, including healthy ones) after gynecologic cancer care who underwent lymphedema treatment at The University of Tokyo and Saiseikai Kawaguchi General Hospital between April 2011 and December 2011. All subjects were referred to our department for lower extremity lymphoscintigraphy and ICG lymphography. The sensitivity and specificity of lymphoscintigraphy and ICG lymphography were calculated for all limbs and for diagnosis of early lymphedema in affected limbs (International Society of Lymphology stages 0 and I). In each analysis, receiver-operating characteristic curves were prepared to compare the accuracy of the two methods. RESULTS: In receiver-operating characteristic analysis of 58 limbs, the area under the curve was 0.72642 for lymphoscintigraphy and 0.90943 for ICG lymphography. In 34 limbs with early lymphedema, the area under the curve was 0.55882 for lymphoscintigraphy and 0.81471 for ICG lymphography. CONCLUSIONS: ICG lymphography was more accurate than lymphoscintigraphy for detecting lymphedema and was particularly useful for diagnosis of early lymphedema. This is clinically important since early diagnosis may permit curative treatment of lymphedema. PMID- 26992344 TI - Accurate nonfluoroscopic guidance and tip location of peripherally inserted central catheters using a conductance guidewire system. AB - BACKGROUND: Bedside placement of peripherally inserted central catheters (PICCs) may result in navigation to undesirable locations, such as the contralateral innominate or jugular vein, instead of the superior vena cava or right atrium. Although some guidance and tip location tools exist, they have inherent limitations because of reliance on physiological measures (eg, chest landmarks, electrocardiogram, etc), instead of anatomical assessment (ie, geometric changes in the vasculature). In this study, an accurate, anatomically based, non-X-ray guidance tool placed on a novel 0.035" conductance guidewire (CGW) is validated for PICC navigation and tip location. METHODS: The CGW system uses electrical conductance recordings to assess changes in vessel cross-sectional area to guide navigation of the PICC tip. Conductance rises and oscillates when going in the correct direction to the superior vena cava/right atrium, but drops when going in the incorrect direction away from the heart. Bench and in vivo studies in six swine were used to confirm the accuracy and repeatability of the PICC placement at various anatomical locations. The PICC tip location was confirmed by direct visualization vs the desired location. RESULTS: CGW PICC guidance was highly accurate and repeatable with virtually no difference between actual and desired catheter tip location. The difference between the CGW PICC location vs the desired target was -0.07 +/- 0.07 cm (6.6% error) on the bench and 0.04 +/- 0.10 cm (5% error) in vivo. No complications or adverse events occurred during CGW usage. CONCLUSIONS: The CGW provides an anatomically based, reproducible, and clinically significant method for PICC navigation and tip location that can improve accuracy, decrease the wait time prior to therapy delivery, decrease cost, and minimize the need for X-ray. These findings warrant clinical evaluation of this navigation tool for PICC line placement. PMID- 26992345 TI - Concomitant aortic and vena caval reconstruction associated with germ-cell tumor resection with creation of a new venous bifurcation. AB - Aortic and vena caval reconstruction associated with tumor resection is very rare. We describe a 22-year-old man with a retroperitoneal metastasis from a germ cell tumor previously treated with chemotherapy who presented with a huge mass involving the infrarenal aorta and the inferior vena cava. He underwent retroperitoneal lymph node dissection with concomitant aortic and caval reconstruction that included customization of a new caval bifurcation. His postoperative recovery was uneventful, and he remained well 36 months after the operation. Complementary follow-up imaging examinations demonstrated that the aortic and venous interposition grafts were patent and that there was no local or distant disease recurrence. PMID- 26992346 TI - Novel endovascular techniques to control in-outflow with dual approach for large pelvic arteriovenous malformation. AB - Here, we present the case of a 51-year-old woman with high-output congestive heart failure caused by a large pelvic arteriovenous malformation. Endovascular treatment that combined arterial nidus embolization with n-butyl 2-cyanoacrylate, coil embolization of the venous component, and balloon-occluded retrograde transvenous obliteration was performed. A promising therapeutic outcome was achieved without recurrence of symptoms over a 3-year period. The combination of these techniques to control arterial inflow and venous outflow is a novel method for the treatment of large pelvic arteriovenous malformation. PMID- 26992347 TI - Open inferior vena cava filter removal after migration. PMID- 26992348 TI - Combined treatment of intracaval uterine leiomyomatosis with pulmonary tumor emboli. PMID- 26992350 TI - Information for readers. PMID- 26992351 TI - Events of interest. PMID- 26992352 TI - Managing Microbial Risks from Indirect Wastewater Reuse for Irrigation in Urbanizing Watersheds. AB - Limited supply of clean water in urbanizing watersheds creates challenges for safely sustaining irrigated agriculture and global food security. On-farm interventions, such as riverbank filtration (RBF), are used in developing countries to treat irrigation water from rivers with extensive fecal contamination. Using a Bayesian approach incorporating ethnographic data and pathogen measurements, quantitative microbial risk assessment (QMRA) methods were employed to assess the impact of RBF on consumer health burdens for Giardia, Cryptosporidium, rotavirus, norovirus, and adenovirus infections resulting from indirect wastewater reuse, with lettuce irrigation in Bolivia as a model system. Concentrations of the microbial source tracking markers pepper mild mottle virus and HF183 Bacteroides were respectively 2.9 and 5.5 log10 units lower in RBF treated water than in the river water. Consumption of lettuce irrigated with river water caused an estimated median health burden that represents 37% of Bolivia's overall diarrheal disease burden, but RBF resulted in an estimated health burden that is only 1.1% of this overall diarrheal disease burden. Variability and uncertainty associated with environmental and cultural factors affecting exposure correlated more with QMRA-predicted health outcomes than factors related to disease vulnerability. Policies governing simple on-farm interventions like RBF can be intermediary solutions for communities in urbanizing watersheds that currently lack wastewater treatment. PMID- 26992355 TI - Theoretical estimation of the rate of photoinduced charge transfer reactions in triphenylamine C60 donor-acceptor conjugate. AB - Fullerene-based molecular heterojunctions such as the [6,6]-pyrrolidine-C60 donor acceptor conjugate containing triphenylamine (TPA) are potential materials for high-efficient dye-sensitized solar cells. In this work, we estimate the rate constants for the photoinduced charge separation and charge recombination processes in TPA-C60 using the unrestricted and time-dependent DFT methods. Different schemes are applied to evaluate excited state properties and electron transfer parameters (reorganization energies, electronic couplings, and Gibbs energies). The use of open-shell singlet or triplet states, several density functionals, and continuum solvation models is discussed. Strengths and limitations of the computational approaches are highlighted. The present benchmark study provides an overview of the expected performance of DFT-based methodologies in the description of photoinduced charge transfer reactions in fullerene heterojunctions. (c) 2016 Wiley Periodicals, Inc. PMID- 26992354 TI - Molecular Control of Atypical Protein Kinase C: Tipping the Balance between Self Renewal and Differentiation. AB - Complex organisms are faced with the challenge of generating and maintaining diverse cell types, ranging from simple epithelia to neurons and motile immune cells [1-3]. To meet this challenge, a complex set of regulatory pathways controls nearly every aspect of cell growth and function, including genetic and epigenetic programming, cytoskeleton dynamics, and protein trafficking. The far reach of cell fate specification pathways makes it particularly catastrophic when they malfunction, both during development and for tissue homeostasis in adult organisms. Furthermore, the therapeutic promise of stem cells derives from their ability to deftly navigate the multitude of pathways that control cell fate [4]. How the molecular components making up these pathways function to specify cell fate is beginning to become clear. Work from diverse systems suggests that the atypical Protein Kinase C (aPKC) is a key regulator of cell fate decisions in metazoans [5-7]. Here, we examine some of the diverse physiological outcomes of aPKC's function in differentiation, along with the molecular pathways that control aPKC and those that are responsive to changes in its catalytic activity. PMID- 26992357 TI - Epidemiology of lawnmower-related injuries in children: A 10-year review. AB - BACKGROUND: Lawnmower-related injuries (LMI) in children are commonly disfiguring and usually preventable. Owing to concerns about the large number and severity of pediatric LMI, we sought to describe the current epidemiology of these injuries in the United States. METHODS: Data were obtained from the 2004 to 2013 National Electronic Surveillance system of the United States Consumer Product Safety Commission for children <=20 years old. Demographic, injury pattern, and treatment data were analyzed. RESULTS: There were an estimated 93,508 LMI, with an incidence of 9,351 LMI per year. The hand and/or fingers (30.1%), lower extremity (16.8%), and face and/or eye (14.0%) were the body parts most commonly injured. Amputations (relative risk [RR]: 11.5; 95% confidence interval [CI]: 11.00 to 12.10; P < .0001) and fractures (RR: 2.82; 95% CI: 2.64 to 3.00; P < .0001) were more likely to require hospitalization. CONCLUSIONS: The estimated annual incidence of LMI in children has remained unchanged over the past decade, and has remained constant when compared with a previous 15-year review using Consumer Product Safety Commission data for the same age group. Reinforcement of prevention strategies and manufacturer redesign of lawnmowers are long overdue. PMID- 26992353 TI - Structural and Molecular Determinants of Membrane Binding by the HIV-1 Matrix Protein. AB - Assembly of HIV-1 particles is initiated by the trafficking of viral Gag polyproteins from the cytoplasm to the plasma membrane, where they co-localize and bud to form immature particles. Membrane targeting is mediated by the N terminally myristoylated matrix (MA) domain of Gag and is dependent on the plasma membrane marker phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Recent studies revealed that PI(4,5)P2 molecules containing truncated acyl chains [tr-PI(4,5)P2] are capable of binding MA in an "extended lipid" conformation and promoting myristoyl exposure. Here we report that tr-PI(4,5)P2 molecules also readily bind to non-membrane proteins, including HIV-1 capsid, which prompted us to re-examine MA-PI(4,5)P2 interactions using native lipids and membrane mimetic liposomes and bicelles. Liposome binding trends observed using a recently developed NMR approach paralleled results of flotation assays, although the affinities measured under the equilibrium conditions of NMR experiments were significantly higher. Native PI(4,5)P2 enhanced MA binding to liposomes designed to mimic non-raft-like regions of the membrane, suggesting the possibility that binding of the protein to disordered domains may precede Gag association with, or nucleation of, rafts. Studies with bicelles revealed a subset of surface and myr-associated MA residues that are sensitive to native PI(4,5)P2, but cleft residues that interact with the 2'-acyl chains of tr-PI(4,5)P2 molecules in aqueous solution were insensitive to native PI(4,5)P2 in bicelles. Our findings call to question extended-lipid MA:membrane binding models, and instead support a model put forward from coarse grained simulations indicating that binding is mediated predominantly by dynamic, electrostatic interactions between conserved basic residues of MA and multiple PI(4,5)P2 and phosphatidylserine molecules. PMID- 26992359 TI - Invited response to Paull et al, errors upstream and downstream to the universal protocol associated with wrong surgery events. PMID- 26992356 TI - A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology. AB - BACKGROUND: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements. METHODS: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier. A prospective, consecutively submitted series of 2673 Bethesda III-VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays. RESULTS: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of three independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%). CONCLUSIONS: A clinical paradigm is proposed, whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay at no added cost. PMID- 26992358 TI - Laparoscopic antrectomy: a safe and definitive treatment in managing type 1 gastric carcinoids. AB - BACKGROUND: Treatment for type 1 gastric carcinoid (T1GC) includes esophagogastroduodenoscopy (EGD), polypectomy, and antrectomy, but few studies compare outcomes. This study assessed risk-benefit ratio to determine the most effective treatment for T1GC. METHODS: A retrospective review of 52 T1GC patients (ages 30 to 88 years; 77% female) presenting to Mount Sinai Medical Center between 2004 and 2012 was conducted. Patient demographics, procedures, and outcomes were reviewed, and patient satisfaction was assessed using a phone administered validated questionnaire. Data were analyzed using SPSS version 20 software. RESULTS: Average EGDs needed per follow-up year was significantly lower for antrectomy than polypectomy or EGD surveillance (.395 vs 1.038 vs 1.380, P = .002). Antrectomy patients exhibited decreased recurrence risk than polypectomy patients (11% vs 44%, P = .049), despite longer follow-up time (6.10 vs 4.39 years, P = .023). CONCLUSIONS: Antrectomy treats T1GC with lower recurrence risk and less postintervention monitoring, whereas allowing patients to avoid the discomfort of repeated EGD surveillance and anxiety over a lingering condition. PMID- 26992360 TI - EEG in non-clinical drug safety assessments: Current and emerging considerations. AB - Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in preclinical safety studies, pre-dose or post-dose EEG assessments are not. Industry practices as they relate to preclinical seizure liability and sleep assessments are not well characterized and the extent of preclinical EEG testing varies between organizations. In the current paper, we discuss the various aspects of preclinical EEG to characterize drug-induced seizure risk and sleep disturbances, as well as describe the use of these data in a regulatory context. An overview of EEG technology-its correct application and its limitations, as well as best practices for setting up the animal models is presented. Sleep and seizure detection are discussed in detail. A regulatory perspective on the use of EEG data is provided and, tying together the previous topics is a discussion of the translational aspects of EEG. PMID- 26992361 TI - Successful implantation of an abdominal aortic blood pressure transducer and radio-telemetry transmitter in guinea pigs - Anaesthesia, analgesic management and surgical methods, and their influence on hemodynamic parameters and body temperature. AB - INTRODUCTION: Guinea pigs (GPs) are a valuable cardiovascular pharmacology model. Implantation of a radio-telemetry system into GPs is, however, challenging and has been associated with a high failure rate in the past. We provide information on a novel procedure for implanting telemetry devices into GPs and we have measured the hemodynamics (arterial blood pressure, BP and heart rate, HR) and core body temperature (BT) in the 24h after surgery. METHODS: Male Hartley GPs (Crl:HA, 350-400g, 6.5weeks, n=16) were implanted with a radio transmitter abdominally and were then monitored continuously (HR, BP and BT) for 24h after surgery. RESULTS: 13 of 16 GPs (81%) survived the surgery. Surgery duration was 94min (min) (range: 76-112min) and anaesthesia duration was 131min (range: 107 158min). GPs lost body weight until 2days after surgery and then regained weight. Mean arterial BP increased from 33.7mmHg directly after surgery to 59.1mmHg after 24h. HR increased from 206bpm directly after surgery to 286bpm at 8h and fell to 251bpm at 24h after implantation. BT was 36 degrees C directly after surgery, fell to 35.4 degrees C until regaining of the righting reflex and then stabilized at 38.5 degrees C after 24h. DISCUSSION: A high survival rate in telemetered GPs is possible. We achieved this through a procedure with minimal stress through habituation and planning, continuous warming during anaesthesia, an optimal anaesthetic and analgesic management, efficient surgical techniques and vitamin C supplementation. PMID- 26992362 TI - Tube formation in the first trimester placental trophoblast cells: Differential effects of angiogenic growth factors and fatty acids. AB - The study aims to investigate whether cytosolic fatty acid-binding protein-4 (FABP4) is involved in angiogenic growth factors- and fatty acid-induced tube formation in first trimester placental trophoblast cells, HTR8/SVneo. We determined the tube formation both at basal as well as stimulated levels in the absence and presence of inhibitors of FABP4 and VEGF signaling pathways. Basal level of tube formation was maximally reduced in the presence of 50 uM of FABP4 inhibitor compared with those by VEGF signaling pathway inhibitors (rapamycin, L NAME, and p38 MAP kinase inhibitor). Whereas docosahexaenoic acid, 22:6n-3 (DHA) , and VEGF-induced tube formation was maximally inhibited by p38 MAP kinase inhibitor (63.7 and 34.5%, respectively), however, leptin-induced tube formation was inhibited maximally by FABP4 inhibitor (50.7%). ANGPTL4 and oleic acid (OA) induced tube formation was not blocked by any of these inhibitors. The FABP4 inhibitor inhibited cell growth stimulated by DHA, leptin, VEGF, and OA (P < 0.05) but was not affected by ANGPTL4. VEGF, leptin, and OA also increased FABP4 protein level in these cells, though the uptake of fatty acids by these cells was not affected by the presence of FABP4 inhibitor. Our data demonstrate that FABP4 may be involved in part in the basal level, and stimulated tube formation by VEGF, DHA, and leptin, whereas it has little or no effect in ANGPTL4- and OA induced tube formation in these cells. Thus, FABP4 may play a differential role in fatty acids and angiogenic growth factors-mediated tube formation in the first trimester trophoblast cells in vitro. PMID- 26992363 TI - Live confocal imaging of Arabidopsis flower buds. AB - Recent advances in confocal microscopy, coupled with the development of numerous fluorescent reporters, provide us with a powerful tool to study the development of plants. Live confocal imaging has been used extensively to further our understanding of the mechanisms underlying the formation of roots, shoots and leaves. However, it has not been widely applied to flowers, partly because of specific challenges associated with the imaging of flower buds. Here, we describe how to prepare and grow shoot apices of Arabidopsis in vitro, to perform both single-point and time-lapse imaging of live, developing flower buds with either an upright or an inverted confocal microscope. PMID- 26992364 TI - A framework for evaluating developmental defects at the cellular level: An example from ten maize anther mutants using morphological and molecular data. AB - In seed plants, anthers are critical for sexual reproduction, because they foster both meiosis and subsequent pollen development of male germinal cells. Male sterile mutants are analyzed to define steps in anther development. Historically the major topics in these studies are meiotic arrest and post-meiotic gametophyte failure, while relatively few studies focus on pre-meiotic defects of anther somatic cells. Utilizing morphometric analysis we demonstrate that pre-meiotic mutants can be impaired in anticlinal or periclinal cell division patterns and that final cell number in the pre-meiotic anther lobe is independent of cell number changes of individual differentiated somatic cell types. Data derived from microarrays and from cell wall NMR analyses allow us to further refine our understanding of the onset of phenotypes. Collectively the data highlight that even minor deviations from the correct spatiotemporal pattern of somatic cell proliferation can result in male sterility in Zea mays. PMID- 26992366 TI - Fins into limbs: Autopod acquisition and anterior elements reduction by modifying gene networks involving 5'Hox, Gli3, and Shh. AB - Two major morphological changes occurred during the fin-to-limb transition: the appearance of the autopod, and the reduction of anterior skeletal elements. In the past decades, numerous approaches to the study of genetic developmental systems involved in patterning of fins/limbs among different taxa have provided clues to better understand the mechanism of the fin-to-limb transition. In this article, I discuss recent progress toward elucidating the evolutionary origin of the autopod and the mechanism through which the multiple-basal bones of ancestral fins were reduced into a single bone (humerus/femur). A particular focus of this article is the patterning mechanism of the tetrapod limb and chondrichthyan fin controlled by gene networks involving the 5'Hox genes, Gli3 and Shh. These recent data provide possible scenarios that could have led to the transformation of fins into limbs. PMID- 26992365 TI - Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures. AB - During growth, individual skull bones overlap at sutures, where osteoblast differentiation and bone deposition occur. Mutations causing skull malformations have revealed some required genes, but many aspects of suture regulation remain poorly understood. We describe a zebrafish mutation in osterix/sp7, which causes a generalized delay in osteoblast maturation. While most of the skeleton is patterned normally, mutants have specific defects in the anterior skull and upper jaw, and the top of the skull comprises a random mosaic of bones derived from individual initiation sites. Osteoblasts at the edges of the bones are highly proliferative and fail to differentiate, consistent with global changes in gene expression. We propose that signals from the bone itself are required for orderly recruitment of precursor cells and growth along the edges. The delay in bone maturation caused by loss of Sp7 leads to unregulated bone formation, revealing a new mechanism for patterning the skull and sutures. PMID- 26992367 TI - Endobronchial ultrasound: an unusual diagnostic tool for pulmonary embolism. AB - Pulmonary thromboembolism (PTE) is an emergent and common pulmonary vascular disease. The most common diagnostic method for PTE is computer-aided tomography angiography. Endobronchial ultrasonography (EBUS) is used in diagnosis and staging of lung cancer via transbronchial needle aspiration from mediastinal lymphadenopathies and central masses. Diagnosis of PTE with EBUS is not common, although this technique helps to monitor pulmonary vasculature. The present case, a 60-year-old female patient to whom EBUS was applied because of mediastinal lymphadenopathy, was diagnosed as incidental PTE. PMID- 26992368 TI - Beyond CTLA-4 and PD-1: Orphan nuclear receptor NR2F6 as T cell signaling switch and emerging target in cancer immunotherapy. AB - Blockade of immune checkpoints has emerged as key strategy in the development of effective cancer therapies. In contrast to cell surface checkpoints like CTLA-4 and PD-1, however, additional cancer therapeutic targets are located inside the effector immune cells. Targeting these alternative checkpoints in cancer immunotherapy with the goal to strengthen the patient's immune system are likely to extend the benefits of cancer immunotherapy in the near future. Along this line, we have defined and validated the orphan nuclear receptor NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) as an intracellular immune checkpoint in effector T cells. NR2F6 acts as a novel master switch of antitumor responses against both transplantable and spontaneous tumors in mice relevant for human cancer. NR2F6 directly represses transcription of key cytokine genes in T effector cells relevant for tumor cell rejection, such as IL-2, IFN and TNFalpha. Thus, in the presence of NR2F6, T cell activation is limited within the tumor microenvironment. This defines NR2F6 as a key checkpoint governing the amplitude of cancer immune surveillance. Based on our study, an approach shall be initiated to identify low molecular weight compounds that selectively interfere with NR2F6 function in the clinic. PMID- 26992369 TI - Fabrication of novel high surface area mushroom gilled fibers and their effects on human adipose derived stem cells under pulsatile fluid flow for tissue engineering applications. AB - The fabrication and characterization of novel high surface area hollow gilled fiber tissue engineering scaffolds via industrially relevant, scalable, repeatable, high speed, and economical nonwoven carding technology is described. Scaffolds were validated as tissue engineering scaffolds using human adipose derived stem cells (hASC) exposed to pulsatile fluid flow (PFF). The effects of fiber morphology on the proliferation and viability of hASC, as well as effects of varied magnitudes of shear stress applied via PFF on the expression of the early osteogenic gene marker runt related transcription factor 2 (RUNX2) were evaluated. Gilled fiber scaffolds led to a significant increase in proliferation of hASC after seven days in static culture, and exhibited fewer dead cells compared to pure PLA round fiber controls. Further, hASC-seeded scaffolds exposed to 3 and 6dyn/cm(2) resulted in significantly increased mRNA expression of RUNX2 after one hour of PFF in the absence of soluble osteogenic induction factors. This is the first study to describe a method for the fabrication of high surface area gilled fibers and scaffolds. The scalable manufacturing process and potential fabrication across multiple nonwoven and woven platforms makes them promising candidates for a variety of applications that require high surface area fibrous materials. STATEMENT OF SIGNIFICANCE: We report here for the first time the successful fabrication of novel high surface area gilled fiber scaffolds for tissue engineering applications. Gilled fibers led to a significant increase in proliferation of human adipose derived stem cells after one week in culture, and a greater number of viable cells compared to round fiber controls. Further, in the absence of osteogenic induction factors, gilled fibers led to significantly increased mRNA expression of an early marker for osteogenesis after exposure to pulsatile fluid flow. This is the first study to describe gilled fiber fabrication and their potential for tissue engineering applications. The repeatable, industrially scalable, and versatile fabrication process makes them promising candidates for a variety of scaffold-based tissue engineering applications. PMID- 26992370 TI - Photo-assisted generation of phospholipid polymer substrates for regiospecific protein conjugation and control of cell adhesion. AB - Novel photo-reactive phospholipid polymers were synthesized for use in the preparation of nonfouling surfaces with protein conjugation capacity. Poly[2 methacryloyloxyethyl phosphorylcholine (MPC)-ran-N-methacryloyl-(l) tyrosinemethylester (MAT)] (P(MPC/MAT)) was synthesized by conventional radical polymerization, with the MAT units capable of being oxidized by 254nm UV irradiation. Because of this photo-oxidation, active species such as catechol and quinone were alternately generated in the copolymer. A silicon wafer was subjected to surface modification through spin coating of P(MPC/MAT) from an aqueous solution for use as a model substrate. The surface was then irradiated several times with UV light. The thickness of the polymer layers formed on the Si wafers was influenced by various parameters such as polymer concentration, UV irradiation time, and composition of the MAT units in P(MPC/MAT). Oxidized MAT units were advantageous not only for polymer adhesion to a solid surface but also for protein conjugation with the adhered polymers. The amount of protein immobilized on UV-irradiated P(MPC/MAT) was dependent on the composition of the MAT units in the polymer. Furthermore, it was confirmed that protein immobilization on the polymer occurred through the oxidized MAT units because the protein adsorption was significantly reduced upon blocking these units through pretreatment with glycine. Conjugation of regiospecific protein could also be achieved through the use of a photomask. In addition, nonspecific protein adsorption was reduced on the non-irradiated regions whose surface was covered with physisorbed P(MPC/MAT). Therefore, P(MPC/MAT) can be used in the preparation of nonfouling substrates, which enable micrometer-sized manipulation of proteins through photo-irradiation. Function of proteins immobilized on MPC copolymers was also confirmed by cell adhesion test. As such, photo-reactive MPC copolymers are suitable for performing controlled protein conjugation and preparing polymer protein hybrid platforms for use in biomedical and diagnostic devices. STATEMENT OF SIGNIFICANCE: Novel photo-reactive phospholipid polymers have been synthesized for immobilization on solid surfaces and regiospecific protein conjugation. Tyrosine residues embedded in 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers could be photo-oxidized, resulting in polymers able to form layers on a solid surface and conjugate with proteins. Moreover, nonspecific biofouling on the surface significantly reduced when the oxidized tyrosine units in the polymer layers were blocked. Upon UV irradiation through a photomask, the UV-exposed tyrosine units were selectively oxidized, forming the only specific regions in which protein conjugation could occur. PMID- 26992372 TI - Combined foraging strategies and soldier behaviour in Nasutitermes aff. coxipoensis (Blattodea: Termitoidea: Termitidae). AB - A range of behavioural strategies and sensory abilities allows animals to minimize costs involved in food search. By building a network of tunnels and presenting a large number of soldiers (i.e., trophically dependent individuals), Nasutitermes spp. termites feature behaviours that imply additional costs during this process. Here we evaluated N. aff. coxipoensis foraging strategies focusing on the role of soldiers during foraging. Field experiments were carried out via nests transplantation to dune areas, and laboratory experiments evaluated termite responses to sternal gland chemical signals from workers and soldiers. N. aff. coxipoensis presented primarily nocturnal foraging. Soldiers typically initiated foraging; however, in established trails, the number of workers was always higher than that of soldiers. The number of trails remained constant over time, while the number of tunnels increased linearly over time. A higher proportion of tunnels originated in surrounding areas than directly from the nests. At observation points with tunnels, there were more stationary than walking soldiers; the opposite was true at observation points without tunnels. In mixed groups, the workers chose to follow soldier chemical signals, and in these groups, soldiers were the first to follow trails. Our results allowed us to identify a not common foraging strategy in termite species; which included the establishment of trails followed by construction of tunnels. Such foraging strategies occur predominantly at night and soldiers play a key role in the foraging process. This foraging strategy reported here seems to be employed to optimize energetic gain. PMID- 26992371 TI - Maternal signature whistle use aids mother-calf reunions in a bottlenose dolphin, Tursiops truncatus. AB - Individual vocal signatures play an important role in parent-offspring recognition in many animals. One species that uses signature calls to accurately facilitate individual recognition is the bottlenose dolphin. Female dolphins and their calves will use their highly individualised signature whistles to identify and maintain contact with one another. Previous studies have shown high signature whistle rates of both mothers and calves during forced separations. In more natural settings, it appears that the calf vocalises more frequently to initiate reunions with its mother. However, little is known about the mechanisms a female dolphin may employ when there is strong motivation for her to reunite with her calf. In this study, we conducted a series of experimental trials in which we asked a female dolphin to retrieve either her wandering calf or a series of inanimate objects (control). Our results show that she used her vocal signature to actively recruit her calf, and produced no such signal when asked to retrieve the objects. This is the first study to clearly manipulate a dolphin's motivation to retrieve her calf with experimental controls. The results highlight that signature whistles are not only used in broadcasting individual identity, but that maternal signature whistle use is important in facilitating mother-calf reunions. PMID- 26992376 TI - Health care professionals' attitudes regarding patient safety: cross-sectional survey. AB - BACKGROUND: Patient safety is being seen as an increasingly important topic in the healthcare fields, and the rise in numbers of patient safety incidents poses a challenge for hospital management. In order to deal with the situation, it is important to know more about health care professionals' attitudes regarding patient safety. This study looks to describe health care professionals' attitudes regarding patient safety, and whether differences exist based on the background factors of study participants. METHODS: A quantitative study using a questionnaire was conducted in three multi-disciplinary hospitals in Western Lithuania. Data was collected in 2014 from physicians, nurses and nurse assistants. RESULTS: The results showed positive safety attitudes, and these were especially related to the respondents' levels of job satisfaction. A respondent's older age was associated with how they evaluated their teamwork climate, safety climate, job satisfaction, and perception of management. Profession, working unit, length of work experience, information received about patient safety during education, further education, and working shifts were all associated with several safety attitude areas. CONCLUSIONS: The safety attitudes of respondents were generally found to be positive. Attitudes related to patient safety issues were positive among health care professionals and opens the door for the open discussion of patient safety and adverse events. However, in future we also need to investigate the knowledge and skills professionals have in relation to patient safety, in order to gain a deeper understanding of the present situation. PMID- 26992378 TI - Adhesion molecules and the extracellular matrix as drug targets for glioma. AB - The formation of tumor vasculature and cell invasion along white matter tracts have pivotal roles in the development and progression of glioma. A better understanding of the mechanisms of angiogenesis and invasion in glioma will aid the development of novel therapeutic strategies. The processes of angiogenesis and invasion cause the production of an array of adhesion molecules and extracellular matrix (ECM) components. This review focuses on the role of adhesion molecules and the ECM in malignant glioma. The results of clinical trials using drugs targeted against adhesion molecules and the ECM for glioma are also discussed. PMID- 26992377 TI - Comparison of intraoperative volume and pressure-controlled ventilation modes in patients who undergo open heart surgery. AB - Respiratory problems occur more frequently in patients who undergo open heart surgery. Intraoperative and postoperative ventilation strategies can prevent these complications and reduce mortality. We hypothesized that PCV would have better effects on gas exchange, lung mechanics and hemodynamics compared to VCV in CABG surgery. Our primary outcome was to compare the PaO2/FiO2 ratio. Patients were randomized into two groups, (VCV, PCV) consisting of 30 individuals each. Two patients were excluded from the study. I/E ratio was adjusted to 1:2 and, RR:10/min fresh air gas flow was set at 3L/min in all patients. In the VCV group TV was set at 8 mL/kg of the predicted body weight. In the PCV group, peak inspiratory pressure was adjusted to the same tidal volume with the VCV group. PaO2/FiO2 was found to be higher with PCV at the end of the surgery. Time to extubation and ICU length of stay was shorter with PCV. Ppeak was similar in both groups. Pplateau was lower and Pmean was higher at the and of the surgery with PCV compared to VCV. The hemodynamic effects of both ventilation modes were found to be similar. PVC may be preferable to VCV in patients who undergo open heart surgery. However, it would be convenient if our findings are supported by similar studies. PMID- 26992379 TI - Bleomycin pharmacokinetics of bolus bleomycin dose in elderly cancer patients treated with electrochemotherapy. AB - PURPOSE: With the aim to determine effective therapeutic window of electrochemotherapy, we analyzed bleomycin pharmacokinetic parameters in elderly patients. METHODS: In prospective clinical study in the treatment of tumors with electrochemotherapy, blood samples of patients older than 65 years were collected after the bolus intravenous injection of bleomycin (15,000 IU/m(2)). In serum samples, quantitative analysis was performed with liquid chromatography coupled to high-resolution mass spectrometry. Based on the data, the pharmacokinetic parameters of bleomycin elimination were determined. RESULTS: Pharmacokinetic analysis of the data revealed a monophasic serum clearance curve, which demonstrates slow elimination of bleomycin, being less than 500 ml/min and a half time of 30 min. CONCLUSIONS: Slow monophasic elimination of bleomycin from serum in elderly patients implies on the longer therapeutic window, from 8 to up to 40 min or even longer post-bleomycin injection for electrochemotherapy. However, prolonged therapeutic bleomycin serum concentrations may also affect the possible adverse effects, such as lung fibrosis and extensive necrosis of tumors due to the uptake of toxic bleomycin concentrations into the tumors. This may imply on lowering of bleomycin dosage, in particular in the elderly patients. PMID- 26992380 TI - Intra-articular injection of mono-iodoacetate induces osteoarthritis of the hip in rats. AB - BACKGROUND: The mechanism for hip pain has been unclear because of a lack of experimental animal models. We aimed to establish an intra-articular injection technique to the rat hip and to document the effect of intra-articular mono iodoacetate (MIA) injection to the rat hip with radiography and histology. METHODS: Using 60 6-week-old male Sprague Dawley rats, 25 MUl of sterile saline (control group; n = 30) and 25 MUl of sterile saline with 2 mg of MIA (MIA group; n = 30) was injected into the right hip joints via posterior approach using a 27G needle. The animals were examined with X-ray and histology 7, 14, 28, 42, and 56 days later (MIA group [n = 6] and control group [n = 6], respectively). RESULTS: The MIA group showed progressive radiographic changes to the hip joint during the experimental period, whereas the control group maintained a normal appearance. The microanatomic appearance was consistent with X-ray images of progressive destruction in the MIA group and normal tissue in the control group. Osteoarthritic (OA) changes became apparent at 42 and 56 days in the MIA group. CONCLUSIONS: We established an intra-articular injection technique to the rat hip, creating a hip OA model in the rat by intra-articular injection of MIA. PMID- 26992382 TI - [Malignant intraorbital tumor: Primary tumor or metastasis?]. PMID- 26992381 TI - A Practice Quality Improvement Project: Reducing Dose of Routine Chest CT Imaging in a Busy Clinical Practice. AB - The purpose of this report is to describe our experience with the implementation of a practice quality improvement (PQI) project in thoracic imaging as part of the American Board of Radiology Maintenance of Certification process. The goal of this PQI project was to reduce the effective radiation dose of routine chest CT imaging in a busy clinical practice by employing the iDose(4) (Philips Healthcare) iterative reconstruction technique. The dose reduction strategy was implemented in a stepwise process on a single 64-slice CT scanner with a volume of 1141 chest CT scans during the year. In the first annual quarter, a baseline effective dose was established using the standard filtered back projection (FBP) algorithm protocol and standard parameters such as kVp and mAs. The iDose(4) technique was then applied in the second and third annual quarters while keeping all other parameters unchanged. In the fourth quarter, a reduction in kVp was also implemented. Throughout the process, the images were continually evaluated to assure that the image quality was comparable to the standard protocol from multiple other scanners. Utilizing a stepwise approach, the effective radiation dose was reduced by 23.62 and 43.63 % in quarters two and four, respectively, compared to our initial standard protocol with no perceived difference in diagnostic quality. This practice quality improvement project demonstrated a significant reduction in the effective radiation dose of thoracic CT scans in a busy clinical practice. PMID- 26992383 TI - [Is (chemo)radiotherapy really the future standard in the treatment of oropharyngeal carcinoma?]. AB - Treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC) requires interdisciplinary collaboration. Besides oncologic control, organ and function preservation are important priorities. One treatment option is primary concomitant chemoradiotherapy (CRT), particularly for locally advanced head and neck cancer. Another option is sequential CRT, where induction chemotherapy may be followed either by radiation alone or by CRT. An important aspect of these modalities is the development of functional sequelae with regards to swallowing as a direct consequence of radiogenic fibrosis, as well as tissue ctoxicity associated with cisplatin-based chemotherapy. Conventional open surgical approaches are being increasingly replaced by transoral surgical modalities with less treatment-related morbidity. As a further, equally important goal of appropriately indicated surgery, adjuvant (C)RT may be omitted or the dose significantly reduced. The advantages of primary surgery over primary CRT may be less obvious in cases still requiring adjuvant treatment, although not necessarily completely eliminated. For patients with human papillomavirus (HPV) driven OPSCC, it is important to note that primary surgery may provide comparable or even increased survival benefit. To date, there is no evidence for a clear advantage of primary CRT over primary surgery in this group. In these cases, a de escalated treatment package may be the preferred option. Here, the application of radioimmunotherapy as well as a reduced radiation dose may minimize long-term treatment-related morbidities. PMID- 26992384 TI - [Hydropic inner ear disease of the vestibular type]. AB - We report the case of a patient with episodic rotational vertigo for years. Ear symptoms were negated. The clinical diagnosis was not clear - Meniere's disease, vestibular migraine and recurrent vertigo after vestibular neuritis all qualified for differential diagnoses. A locally enhanced inner-ear MRI established clarity by showing an endolymphatic hydrops in the vestibulum. Besides the classical triad of Meniere's disease there are other clinical appearances of endolymphatic hydrops, which can be visualized with inner-ear MRI. PMID- 26992385 TI - Treatment in elderly patients with head and neck cancer : A challenging dilemma. AB - Despite the increasing number of elderly patients requiring treatment for head and neck cancer, there is insufficient available evidence about the oncological results of treatment and its tolerability in such patients. Owing to comorbidities, elderly patients often need complex evaluation and pretreatment management, which often results in their exclusion from clinical trials. The question of which patients constitute the highest-risk groups regarding treatment related morbidity and mortality, and who can tolerate and benefit from aggressive treatment, has not been adequately studied. Biologic rather than chronologic age should be a more important factor in treatment protocols. Age-specific prospective clinical studies are needed on the treatment of head and neck cancer in elderly patients. PMID- 26992386 TI - Choice Experiments to Quantify Preferences for Health and Healthcare: State of the Practice. AB - Stated-preference methods increasingly are used to quantify preferences in health economics, health technology assessment, benefit-risk analysis and health services research. The objective of stated-preference studies is to acquire information about trade-off preferences among treatment outcomes, prioritization of clinical decision criteria, likely uptake or adherence to healthcare products and acceptability of healthcare services or policies. A widely accepted approach to eliciting preferences is discrete-choice experiments. Patient, physician, insurant or general-public respondents choose among constructed, experimentally controlled alternatives described by decision-relevant features or attributes. Attributes can represent complete health states, sets of treatment outcomes or characteristics of a healthcare system. The observed pattern of choice reveals how different respondents or groups of respondents implicitly weigh, value and assess different characteristics of treatments, products or services. An important advantage of choice experiments is their foundation in microeconomic utility theory. This conceptual framework provides tests of internal validity, guidance for statistical analysis of latent preference structures, and testable behavioural hypotheses. Choice experiments require expertise in survey-research methods, random-utility theory, experimental design and advanced statistical analysis. This paper should be understood as an introduction to setting up a basic experiment rather than an exhaustive critique of the latest findings and procedures. Where appropriate, we have identified topics of active research where a broad consensus has not yet been established. PMID- 26992387 TI - Combined antenatal therapy with retinoic acid and tracheal occlusion in a rat model of congenital diaphragmatic hernia. AB - AIM: To investigate the effect of combined prenatal treatment with retinoic acid (RA) and tracheal occlusion (TO) on the pulmonary vascular morphology and expression of vascular endothelial growth factors (VEGF) and its receptors in a rat model of congenital diaphragmatic hernia (CDH). MATERIAL AND METHODS: Rats were given nitrofen at 9 days of gestation followed by no treatment (CDH), RA (CDH + RA), TO (CDH + TO), or both (CDH + RA + TO) (n = 16). We measured the median wall thickness of the pulmonary arterioles (MWT) and analyzed the expression of VEGF and its receptors (VEGFR1 and VEGFR2). RESULTS: Compared to control animals, CDH had increased MWT (44 +/- 15 vs. 58 +/- 7; p < 0.05) and decreased expression of VEGF, VEGFR1, and VEGFR2 (p < 0.05). Treatment with RA or TO alone, and RA + TO reduced the MWT (46 +/- 9, 42 +/- 11, 46 +/- 8, respectively) and improved the expression of VEGF, VEGFR1, and VEGFR2 compared to CDH (p < 0.05). However, the combination of RA + TO did not confer additional benefit in the reduction of the MWT or in increasing the VEGF and its receptors compared to either treatment alone. CONCLUSION: Antenatal treatment with either RA or TO improved the MWT and expression of VEGF and its receptors in a CDH rat model. However, combined treatment with RA + TO was not superior to either treatment alone. PMID- 26992388 TI - Update on Enteral Stents. AB - OPINION STATEMENT: The recent advances in enteral stents design and composition introduced novel usage and indications, heading to a continuous addition of prostheses application in clinical practice. Since the first use to palliate malignant diseases, improving patient's quality of life, in the last decades we assisted to a large spread, often becoming a first choice treatment in GI disorders. Indeed, the clinical indication of gastrointestinal stents includes endoscopic treatment of fistula and leaks besides the well-established role of restoring lumen patency in benign and malignant conditions. Several different kind of stents have been developed, each one with its own characteristics and benefits, including self-expandable plastic and metal stents, available as uncovered, partially covered, and fully covered as well as biodegradable stents. Recently, new drug-eluting stents, working both as palliative treatment and as local chemotherapy, are under evaluation. This review aims to critically evaluate the most recently published literature about enteral stents and to address endoscopists' choice for a better patient management. PMID- 26992389 TI - Interactive effect of water and nitrogen regimes on plant growth, root traits and water status of old and modern durum wheat genotypes. AB - MAIN CONCLUSIONS: The selection of the ideal root drought adaptive traits should take into account the production and maintenance of root tissues alongside the capacity to capture soil resources. Ten old and modern Spanish durum wheat (Triticum turgidum L. var durum) genotypes were grown in lysimeters under two contrasting water and nitrogen regimes to study the effect of such growth conditions on: (1) the aerial biomass, (2) the growth and structure of the roots and (3) the relationships of the root structure with aerial biomass, photosynthetic and transpirative characteristics and water use efficiency. Both high water and nitrogen regimes significantly increased aerial biomass. Root dry biomass and root length increased and decreased in response to improved water supply and nitrogen regimes, respectively. No significant correlations were detected between aerial biomass and any root trait under well-watered conditions. Under water stress aerial biomass was negatively correlated with root dry biomass, root length and root weight density and positively correlated with the specific root length, particularly for the subset of old genotypes. The high nitrogen regime significantly enriched the carbon isotope composition of the flag leaf (delta (13)CFL) and hindered the effect of the high water regime on decreasing delta (13)CFL enrichment. Thus, positive correlations of aerial biomass with delta (13)CFL were detected regardless of the water regime. The study revealed: (1) the importance of root traits for higher aerial biomass under the low water regime; (2) that the interaction between nitrogen and the water regime may affect the predictive nature of the delta (13)C in drought breeding programs; and (3) the selection of the ideal root system structure should take into account the metabolic costs of the production and maintenance of root tissues alongside the capacity of capturing resources. PMID- 26992390 TI - Survival and quality of life after surgical aortic valve replacement in octogenarians. AB - BACKGROUND: In patients with symptomatic severe aortic stenosis, advanced age is often a reason for a transcatheter rather than surgical aortic valve replacement. In this pre-transcatheter cohort we had the unique opportunity to study outcomes after surgical aortic valve replacement for severe aortic stenosis in patients who might currently be triaged to a percutaneous approach. METHODS: In a prospective single-center cohort study we compared the incidence of peri operative complications, mortality, and health-related quality of life in octogenarians versus patients aged <80 years. The quality of life was measured using the SF-36 questionnaire and expressed as a physical and mental component score (PCS and MCS respectively); a score of 50 equals the average score in the age-matched general population. The association between age and the component scores at one-year follow-up was studied with the use of linear regression, corrected for a set of confounding variables. RESULTS: We included 762 patients, of whom 21.4 % was aged >80 and 49.0 % underwent concomitant revascularization. In octogenarians, the incidence of post-operative delirium was 11.0 %, which was higher than in patients aged below 80 (6.2 %, p = 0.034); the operative mortality (1.9 % vs. 2.9 %; p = 0.59) and long-term survival were not different however (log-rank p = 0.75). In octogenarians, the quality of life was impaired 30-days after surgery (PCS 45.01, p < 0.001; MCS 48.21, p = 0.04), which improved towards or above normal values at one-year follow-up (PCS: 49.92, p = 0.67, MCS: 52.55, p < 0.001). After correction for confounding, age was not significantly associated with the one-year PCS (beta 0.08 per year, p = 0.34) or MCS (beta 0.08 per year, p = 0.32). CONCLUSIONS: This pre-transcatheter study showed that surgical aortic valve replacement in octogenarians could be performed with very low mortality, and with a relevant and significant increase of the quality of life towards normal values. Also, age was not associated with a lower PCS or MCS one-year after surgery. PMID- 26992391 TI - Determination of the Michaelis-Menten kinetics and the genes expression involved in phyto-degradation of cyanide and ferri-cyanide. AB - Hydroponic experiments were conducted with different species of plants (rice, maize, soybean and willow) exposed to ferri-cyanide to investigate the half saturation constant (K M ) and the maximal metabolic capacity (v max ) involved in phyto-assimilation. Three varieties for each testing species were collected from different origins. Measured concentrations show that the uptake rates responded biphasically to ferri-cyanide treatments by showing increases linearly at low and almost constant at high concentrations from all treatments, indicating that phyto-assimilation of ferri-cyanide followed the Michaelis-Menten kinetics. Using non-linear regression, the highest v max was by rice, followed by willows. The lowest v max was found for soybean. All plants, except maize (DY26) and rice (XJ12), had a similar K M value, suggesting the same enzyme was active in phyto assimilation of ferri-cyanide. Transcript level, by real-time quantitative PCR, of enzymes involved in degradation of cyanides showed that the analyzed genes were differently expressed during different cyanides exposure. The expression of CAS and ST genes responded positively to KCN exposure, suggesting that beta-CAS and ST pathways were two possible pathways for cyanide detoxification in rice. The transcript level of NIT and ASPNASE genes also showed a remarkable up regulation to KCN, implying the contribution to the pool of amino acid aspartate, which is an end product of CN metabolism. Up-regulation of GS genes suggests that acquisition of ammonium released from cyanide degradation may be an additional nitrogen source for plant nutrition. Results also revealed that the expressions of these genes, except for GS, were relatively constant during iron cyanide exposure, suggesting that they are likely metabolized by plants through a non defined pathway rather than the beta-CAS pathway. PMID- 26992392 TI - Prospective Measurement of Daily Health Behaviors: Modeling Temporal Patterns in Missing Data, Sexual Behavior, and Substance Use in an Online Daily Diary Study of Gay and Bisexual Men. AB - Daily diary and other intensive longitudinal methods are increasingly being used to investigate fluctuations in psychological and behavioral processes. To inform the development of this methodology, we sought to explore predictors of and patterns in diary compliance and behavioral reports. We used multilevel modeling to analyze data from an online daily diary study of 371 gay and bisexual men focused on sexual behavior and substance use. We found that greater education and older age as well as lower frequency of substance use were associated with higher compliance. Using polynomial and trigonometric functions, we found evidence for circaseptan patterns in compliance, sexual behavior, and substance use, as well as linear declines in compliance and behavior over time. The results suggest potential sources of non-random patterns of missing data and suggest that trigonometric terms provide a similar but more parsimonious investigation of circaseptan rhythms than do third-order polynomial terms. PMID- 26992393 TI - Self-reported Recent PrEP Dosing and Drug Detection in an Open Label PrEP Study. AB - Monitoring adherence to pre-exposure prophylaxis (PrEP) is part of the recommended package for PrEP prescribing, yet ongoing concerns about how to do so confidently are exacerbated by gross discrepancies in reported and actual use in clinical trials. We evaluated concordance between reports of recent PrEP dosing collected via neutral interviewing and drug quantitation in the iPrEx open-label extension, where participants (n = 1172) had the choice to receive or not receive PrEP. Self-report of recent dosing (at least one PrEP dose in the past 3-day) was the most common report (84 % of participants), and among these 83 % did have quantifiable levels of drug. The vast majority of those reporting no doses in the past 3-day (16 % of the sample) did not have quantifiable levels of drug (82 %). Predictors of over-report of dosing included younger age and lower educational attainment. Monitoring recent PrEP use through neutral interviewing may be a productive approach for clinicians to consider in implementation of real-world PrEP. Strategies to capture longer term or prevention-effective PrEP use, particularly for younger cohorts, are needed. PMID- 26992395 TI - A Systematic Review of Published Respondent-Driven Sampling Surveys Collecting Behavioral and Biologic Data. AB - Reporting key details of respondent-driven sampling (RDS) survey implementation and analysis is essential for assessing the quality of RDS surveys. RDS is both a recruitment and analytic method and, as such, it is important to adequately describe both aspects in publications. We extracted data from peer-reviewed literature published through September, 2013 that reported collected biological specimens using RDS. We identified 151 eligible peer-reviewed articles describing 222 surveys conducted in seven regions throughout the world. Most published surveys reported basic implementation information such as survey city, country, year, population sampled, interview method, and final sample size. However, many surveys did not report essential methodological and analytical information for assessing RDS survey quality, including number of recruitment sites, seeds at start and end, maximum number of waves, and whether data were adjusted for network size. Understanding the quality of data collection and analysis in RDS is useful for effectively planning public health service delivery and funding priorities. PMID- 26992394 TI - Partnership-Level Analysis of African American Women's Risky Sexual Behavior in Main and Non-Main Partnerships. AB - The majority of research on risky sexual behavior in African American women has examined global associations between individual-level predictors and behavior. However, this method obscures the potentially significant impact of the specific relationship or relationship partner on risky sexual behavior. To address this gap, we conducted partnership-level analysis of risky sexual behavior among 718 African American women recruited from HIV counseling, testing, and referral sites in four states. Using mixed model regressions, we tested relationships between condomless vaginal intercourse with men and variables drawn from the Theory of Planned Behavior, Theory of Gender and Power, and previous research specifically on sexual risks among African American women. Significant associations with risky sexual behavior indicate the need for continued emphasis on condom attitudes, condom negotiation behaviors, and overcoming partner resistance to condoms within both main and non-main partnerships when implementing interventions designed to address HIV and sexually transmitted infection risks among African American women. PMID- 26992396 TI - Fertility rates among very young adolescent women: temporal and spatial trends in Brazil. AB - BACKGROUND: We assessed whether the reported decrease in fertility rates among 15 to 19 years old Brazilian adolescents has met with a parallel decrease in very young adolescent (10 to 14 years old) fertility rates. So we explored temporal trends for fertility rates among very young adolescents between 2000 and 2012 for Brazil as a whole, its regions and states; and also analyzed the spatial distribution of fertility rates among Brazilian municipalities in the years 2000 and 2012. METHODS: We used data from the Information System on Live Births to calculate the rates. To examine the temporal trends, we used linear regression for time series with Prais-Winsten estimation, including the annual percentage change, for the country, regions, and states. To analyze the spatial distribution among Brazilian municipalities, we calculated the Global Moran Index and created a local Moran significance and cluster map through Local Indicators of Spatial Association (LISA). We also elaborated a thematic map with the rates using empirical Bayesian estimation. RESULTS: Brazilian very young adolescent fertility rates remained high and stable throughout the 2000 to 2012 period, and significantly decreased in three out of 26 states, and in the federal district. On the other hand, an increase was observed in two Northern and Northeastern states. The rates were spatially dependent in Brazilian municipalities (Moran Index = 0.22 in 2012; p = 0.05). The maps indicated a heterogeneous distribution of the rates, with high-rate clusters predominant in the North and low-rate clusters predominant in the South, Southeast, and Midwest. CONCLUSIONS: Our findings indicate that Brazilian very young adolescent fertility rates have not decreased in parallel with adolescent fertility rates as they remain high and did not decrease from 2000 and 2012, even though a few states presented a decrease. Thus, these phenomena probably have distinct underlying causes that warrant further elucidation. Progress in this field is crucial for the development of specific policies and programs focused on very young adolescents. PMID- 26992397 TI - Management of Primary Gastrointestinal Non-Hodgkin Lymphomas: a Population-Based Survival Analysis. AB - INTRODUCTION: Primary gastrointestinal non-Hodgkin lymphomas (PGINHL) are a heterogeneous group of rare GI malignancies with limited data to guide management. This study describes management of PGINHL in a population-based registry and aims to determine the association between receipt of surgery and long-term survival. METHODS: All adults diagnosed with PGINHL over 27 years in the Surveillance, Epidemiology, and End Results were identified (excluding mucosa associated lymphoid tissue lymphomas). Demographic and clinical characteristics were assessed. Survival was compared using the log-rank method. Cox hazard modeling was used to determine independent prognostic factors. RESULTS: We identified 16,129 patients. The majority were of gastric origin and had diffuse large B cell histology. Surgery was performed in 46.9 % of patients, not recommended in 41.8 % and recommended but not performed in 10.1 %. Overall 1-year and 5-year survival rates were 65.6 and 35.6 %, respectively. Patients undergoing surgery had a 5-year survival of 43.6 % compared to 34.8 % for whom surgery was recommended but not performed (p < .0001), (receipt of chemotherapy not available). Female gender, gastric location, follicular or mantle cell histology, and radiation therapy were associated with improved survival. CONCLUSIONS: Nearly 50 % of PGINHL patients underwent surgery. Surgery was not associated with improved survival. More prospective, case-matched studies are needed to guide management. PMID- 26992398 TI - Calcified Cystic Lesion of the Pancreas. AB - Pancreatic cystic lesion is a relatively uncommon condition with an estimated prevalence of 2 % in the general population. In the past two decades, there has been a dramatic increase in the prevalence of pancreatic cystic lesions because of the widespread use of high-resolution imaging, as well as the aging of the population. Pancreatic cystic lesions cover a wide spectrum of pathology and can range from obviously benign to borderline malignant potential lesions to overt malignancy. Though the presence of mural nodules, septa-like structures, or calcification on imaging examination contributes to the differential diagnosis, preoperatively determining the biological nature of these cystic lesions is sometimes challenging. In this paper, we report a rare case of pancreatic cystic lesion with an egg-shell like calcification. Complete resection was performed and histological examination confirmed the diagnosis of calcified pancreatic pseudocyst. PMID- 26992399 TI - Active Case Finding Among Homeless People as a Means of Reducing the Incidence of Pulmonary Tuberculosis in General Population. AB - The incidence of tuberculosis (TB) declined more than two-fold, compared with the national average, in the northeastern region of Poland in the period of 2003 2012. During that time, four programs of active case finding of TB were conducted as part of which a total of 944 homeless individuals were examined and 21 cases of active TB were detected. The objective of the present study was to find out whether the observed beneficial epidemiological trend could be a result of those programs. We addressed the issue of how the active case finding programs in the homeless community affected the TB incidence in the general population using a modified crisscross SIS-type (Susceptible - Infected - Susceptible) model which describes the dynamics of TB spread between the homeless and non-homeless populations. The values calculated from our model proved highly congruent with the actual epidemiological data. Our analysis showed a significant decline in TB incidence within 1 year of completion of each active case finding program. The model shows that each identified and cured case in the homeless community reduced the number of new cases in the general population by 3-4 within 1 year and by up to 20 within 5 years. PMID- 26992401 TI - Infection with a Shoot-Specific Fungal Endophyte (Epichloe) Alters Tall Fescue Soil Microbial Communities. AB - Tall fescue (Schedonorus arundinaceus) is a widespread grass that can form a symbiotic relationship with a shoot-specific fungal endophyte (Epichloe coenophiala). While the effects of fungal endophyte infection on fescue physiology and ecology have been relatively well studied, less attention has been given to how this relationship may impact the soil microbial community. We used high-throughput DNA sequencing and phospholipid fatty acid analysis to determine the structure and biomass of microbial communities in both bulk and rhizosphere soils from tall fescue stands that were either uninfected with E. coenophiala or were infected with the common toxic strain or one of several novel strains of the endophyte. We found that rhizosphere and bulk soils harbored distinct microbial communities. Endophyte presence, regardless of strain, significantly influenced soil fungal communities, but endophyte effects were less pronounced in prokaryotic communities. E. coenophiala presence did not change total fungal biomass but caused a shift in soil and rhizosphere fungal community composition, increasing the relative abundance of taxa within the Glomeromycota phylum and decreasing the relative abundance of genera in the Ascomycota phylum, including Lecanicillium, Volutella, Lipomyces, Pochonia, and Rhizoctonia. Our data suggests that tripartite interactions exist between the shoot endophyte E. coenophiala, tall fescue, and soil fungi that may have important implications for the functioning of soils, such as carbon storage, in fescue-dominated grasslands. PMID- 26992402 TI - Suicide notes and cadaveric organ donation. AB - A suicide note is an important tool for medico-legal investigation on the manner and circumstances surrounding the death. It can also act as a facilitator for organ donation when the victim expresses their wish to do so. This article cites four examples, where the victims had specifically mentioned a "last wish" to donate their organs. The importance of such "expressed consent" in suicide notes is discussed. Such observations are not found in available scientific literature and are of importance in countries where there is a long waiting list for organ recipients and a very large number of suicidal deaths. PMID- 26992400 TI - New features of desiccation tolerance in the lichen photobiont Trebouxia gelatinosa are revealed by a transcriptomic approach. AB - Trebouxia is the most common lichen-forming genus of aero-terrestrial green algae and all its species are desiccation tolerant (DT). The molecular bases of this remarkable adaptation are, however, still largely unknown. We applied a transcriptomic approach to a common member of the genus, T. gelatinosa, to investigate the alteration of gene expression occurring after dehydration and subsequent rehydration in comparison to cells kept constantly hydrated. We sequenced, de novo assembled and annotated the transcriptome of axenically cultured T. gelatinosa by using Illumina sequencing technology. We tracked the expression profiles of over 13,000 protein-coding transcripts. During the dehydration/rehydration cycle c. 92 % of the total protein-coding transcripts displayed a stable expression, suggesting that the desiccation tolerance of T. gelatinosa mostly relies on constitutive mechanisms. Dehydration and rehydration affected mainly the gene expression for components of the photosynthetic apparatus, the ROS-scavenging system, Heat Shock Proteins, aquaporins, expansins, and desiccation related proteins (DRPs), which are highly diversified in T. gelatinosa, whereas Late Embryogenesis Abundant Proteins were not affected. Only some of these phenomena were previously observed in other DT green algae, bryophytes and resurrection plants, other traits being distinctive of T. gelatinosa, and perhaps related to its symbiotic lifestyle. Finally, the phylogenetic inference extended to DRPs of other chlorophytes, embryophytes and bacteria clearly pointed out that DRPs of chlorophytes are not orthologous to those of embryophytes: some of them were likely acquired through horizontal gene transfer from extremophile bacteria which live in symbiosis within the lichen thallus. PMID- 26992403 TI - Recent advances in synthetic carbohydrate-based human immunodeficiency virus vaccines. AB - An effective vaccine for human immunodeficiency virus (HIV) is urgently needed to prevent HIV infection and progression to acquired immune deficiency syndrome (AIDS). As glycosylation of viral proteins becomes better understood, carbohydrate-based antiviral vaccines against special viruses have attracted much attention. Significant efforts in carbohydrate synthesis and immunogenicity research have resulted in the development of multiple carbohydrate-based HIV vaccines. This review summarizes recent advances in synthetic carbohydrate-based vaccines design strategies and the applications of these vaccines in the prevention of HIV. PMID- 26992404 TI - Non-neoplastic diseases of the fallopian tube: MR imaging with emphasis on diffusion-weighted imaging. AB - OBJECTIVE: We illustrate the magnetic resonance imaging (MRI) features of non neoplastic tubaric conditions. BACKGROUND: A variety of pathologic non-neoplastic conditions may affect the fallopian tubes. Knowledge of their imaging appearance is important for correct diagnosis. With recent advances in MRI, along with conventional MR sequences, diffusion-weighted imaging (DWI) sequences are available and may improve lesion characterization by discriminating the nature of the content of the dilated tube. Tubal fluid with low signal intensity on T1 weighted images, high signal intensity on T2-weighted images and no restricted diffusion on DWI is indicative of hydrosalpinx. Content with high signal intensity on T1-weighted images and restricted diffusion on DWI is suggestive of hematosalpinx associated with endometriosis or tubal pregnancy. A dilated tube with variable or heterogeneous signal intensity content on conventional MR sequences and restricted diffusion on DWI may suggest a pyosalpinx or tubo ovarian abscess. We describe morphological characteristics, MR signal intensity features, enhancement behaviour and possible differential diagnosis of each lesion. CONCLUSION: MRI is the method of choice to study adnexal pelvic masses. Qualitative and quantitative functional imaging with DWI can be of help in characterization of tubaric diseases, provided that findings are interpreted in conjunction with those obtained with conventional MRI sequences. TEACHING POINTS: * Nondilated fallopian tubes are not usually seen on MR images. * MRI is the method of choice to characterize and localize utero-adnexal masses. * MRI allows characterization of lesions through evaluation of the fluid content's signal intensity. * DWI in conjunction with conventional MRI sequences may improve tissue characterization. * Pelvic inflammatory disease is the most common tubal pathology. PMID- 26992406 TI - Comment on "Safety and tolerability of Kinesio(r) Taping in patients with arm lymphedema: medical device clinical study". Taner Dandinoglu, Murat Karadeniz, Ozgur Dandin, Ali Onay. PMID- 26992405 TI - Sulfiredoxin-1 protects against simulated ischaemia/reperfusion injury in cardiomyocyte by inhibiting PI3K/AKT-regulated mitochondrial apoptotic pathways. AB - Reactive oxygen species (ROS)-triggered cardiac cell injury is recognized as the major contributor for the pathogenesis progression of ischaemic cardiovascular diseases. Sulfiredoxin-1 (Srx-1) is an endogenous antioxidant and exerts the crucial neuroprotective effects in cerebral ischaemia. However, its function and the underlying mechanism in ischaemic heart diseases remain poorly defined. Here, a dramatical decrease in Srx-1 was validated in H9c2 cardiomyocytes upon simulated ischaemia-reperfusion (SI/R) injury. Moreover, Srx-1 protected H9c2 cells from SI/R-injured injury as the evidences that Srx-1 up-regulation attenuated the inhibitory effects on cell viability, lactate dehydrogenase (LDH) and cell apoptosis upon SI/R treatment. Knockdown of Srx-1 accelerated cell injury upon SI/R. Mechanism assay corroborated that SI/R treatment noticeably aggravated the loss of mitochondrial membrane potential (Deltapsim), which was remarkably abated in Ad-Srx-1 groups. Importantly, Srx-1 elevation substantially reduced cytochrome c release, the activity of caspase-9 and caspase-3, accompany with the subsequent decrease in the cleavage of poly (ADP ribose) polymerase (PARP). Concomitantly, overexpression of Srx-1 also decreased the expression of pro-apoptosis protein Bax and increased anti-apoptotic Bcl-2 expression. Further analysis substantiated that Srx-1 treatment remarkably induced the activation of PI3K/AKT signalling. Preconditioning with LY294002 dramatically decreased Srx-1 enhanced cell resistance to SI/R injury. Importantly, LY294002 mitigated the inhibitory effects of Srx-1 on Deltapsim loss, cytochrome c release, caspase-9/3 activity, and the expression of Bcl-2 family. Together, these results suggested that Srx-1 might protect cardiomyocyte injury upon SI/R by suppressing PI3K/AKT mediated mitochondria dependent apoptosis, revealing a promising therapeutic agent against ischaemic cardiovascular diseases. PMID- 26992408 TI - 'Am I really ready to go home?': a qualitative study of patients' experience of early discharge following an enhanced recovery programme for liver resection surgery. AB - PURPOSE: Fast-track surgery or enhanced recovery programmes (ERP) have been shown to improve patient outcomes with shorter post-operative recovery times, fewer complications and more cost-effective care amongst the reported benefits. Traditionally, the effectiveness of ERPs have been assessed by measuring clinical outcomes, with the patient experience often being neglected. The aim of this qualitative study was to ascertain patients' expectations and experiences of fast track surgery and recovery at home within the setting of an enhanced recovery programme (ERP). METHOD: Twenty patients enrolled in the treatment group of the randomised controlled trial 'Enhanced recovery in liver resection surgery' were interviewed pre-operatively and 6 weeks post-surgery. Transcripts were analysed using thematic analysis. RESULTS: Patients approached the surgery with a sense of renewed hope. Involvement with the ERP was viewed positively, and having milestones to aim for gave patients a sense of purpose. Many felt that real recovery from surgery began at home and so felt positive about having an early discharge. Patients did report some concerns about being discharged early and those who failed to meet milestones or were readmitted to hospital experienced this as failure. CONCLUSIONS: This qualitative data demonstrates some of the complexities of patients' expectations and experiences of the ERP. Whilst patients generally experience the ERP positively, they also have concerns about the process. The study highlights areas where additional support may be needed for patients enrolled in ERPs and discharged early. PMID- 26992407 TI - Vulnerable characteristics and interest in wellness programs among head and neck cancer caregivers. AB - PURPOSE: Head and neck cancer (HNC) caregivers have poorer psychological health compared to patients and the general population but have not yet been targeted for wellness programs to reduce adverse psychosocial or physical health outcomes. To inform development of such programs, we identified potential vulnerabilities to poor outcomes and examined wellness program preferences among HNC caregivers. We also examined whether interest in wellness programs varied by potential vulnerabilities among HNC caregivers. METHODS: Surveys were administered to caregivers (n = 33) of HNC patients undergoing major surgery. Sociodemographic factors, caregiving characteristics, psychosocial functioning, and health behavior data were collected. Fisher's exact tests and t tests were used to examine characteristics associated with interest in the different types of wellness programs. RESULTS: Many caregivers reported a heavy caregiving load (88 % live with patient and 73 % provide daily care), a smoking history (42 %), and compromised psychosocial functioning (45 % with depressive symptoms and 33 % with anxiety above population norms). Most caregivers were interested in wellness programs focused on diet/exercise (71.9 %); cancer education (66.7 %); stress reduction (63.6 %); and finances, caregiving, and well-being (57.6 %). Caregivers endorsed highest interest in programs offered during the patient's medical treatment (63.6 %), and mail was the preferred program format (50.0 %). Those with more depressive symptoms reported more interest in programs focused on cancer education (p = 0.03); stress reduction (p = 0.05); and educational classes on finances, caregiving, and well-being (p = 0.01). CONCLUSIONS: Wellness programs offering a menu of options should be developed for HNC caregivers. PMID- 26992409 TI - The trajectory of neurotoxic side effects' impact on daily life: a qualitative study. AB - PURPOSE: The purpose of this study was to explore the experiences of oxaliplatin induced neurotoxic side effects among patients with colorectal cancer (CRC) and how these side effects influenced their daily lives over time. METHODS: To assess neurotoxic side effects, ten patients were repeatedly interviewed. The patients were recruited from two hospitals in south of Sweden, had stage II-III CRC, and had been treated with adjuvant oxaliplatin postoperatively, from November 2013 to October 2015. They had received FOLFOX and XELOX, with a mean total dose of 791 mg oxaliplatin. After completed chemotherapy, at 3, 6, and 12 months into the post-treatment phase, 25 interviews were conducted and thematic analysis was used according to Braun and Clarke. RESULTS: Oxaliplatin-induced neurotoxicity affects patients in several ways in the long term. Four themes were identified: Expectation of cure, Dubiety, Normalization, and Learn to live with neurotoxicity. The findings of this study describe the trajectory of neurotoxicity and its impact on these patients' life situation. The findings confirmed that neurotoxicity is multi-faceted and that the experience of it changes over time. CONCLUSION: The desire to survive stimulates adaptations and strategies to manage daily life, and patients learn to live with the neurotoxic side effects. This study provides evidence that these patients need individual attention and support during the trajectory of neurotoxic side effects. Current care provision is inadequate due to a lack of knowledge of the ways in which neurotoxicity impacts the patient's daily life. This study provides insights that could be used to develop a more person-centered care. PMID- 26992410 TI - The BMA's guidance on conscientious objection may be contrary to human rights law. AB - It is argued that the current policy of the British Medical Association (BMA) on conscientious objection is not aligned with recent human rights developments. These grant a right to conscientious objection to doctors in many more circumstances than the very few recognised by the BMA. However, this wide-ranging right may be overridden if the refusal to accommodate the conscientious objection is proportionate. It is shown that it is very likely that it is lawful to refuse to accommodate conscientious objections that would result in discrimination of protected groups. It is still uncertain, however, in what particular circumstances the objection may be lawfully refused, if it poses risks to the health and safety of patients. The BMA's policy has not caught up with these human rights developments and ought to be changed. PMID- 26992412 TI - Weekend effect in endovascular stroke treatment: do treatment decisions, procedural times, and outcome depend on time of admission? AB - BACKGROUND: Epidemiologic studies identified a 'weekend effect' or 'out-of-hours effect', which implies that procedural and clinical outcomes of patients with stroke, who are admitted out-of-hours, are less favorable than for patients admitted during working-hours. OBJECTIVE: To determine (1) whether our procedural times and clinical outcome were affected by an out-of-hours effect and (2) whether the decision in favor of, or against, endovascular stroke treatment (EST) depends on the time of admission. METHODS: Between February 2010 and January 2015, 6412 consecutive patients presenting with symptoms of acute ischemic stroke were evaluated for EST eligibility according to established local protocols and generally accepted consensus criteria, and dichotomized into working-hours and out-of-hours cohorts according to admission times. Within both groups, patients given EST were identified and the rate of treatment decision, procedural times, and clinical outcome were compared and analyzed. RESULTS: Clinical and radiological features of patients admitted in working-hours and out-of-hours did not differ significantly. Procedural times and clinical outcome were not affected by an out-of-hours effect (p>=0.054). 221/240 (92.1%) out-of-hours patients and 154/166 (92.8%) working-hours patients who were eligible for EST were transferred to the angiography suite for EST (p=0.798). The rationale not to treat patients who were eligible for EST did not differ between working-hours and out-of-hours admission (p=0.756). CONCLUSIONS: It is possible to produce competitive procedural times regardless of the time of admission and to prevent a treatment decision bias when standard operating procedures are applied consistently. PMID- 26992411 TI - Syphilis incidence among men who have sex with men in China: results from a meta analysis. AB - The recent upsurge of syphilis infections among men who have sex with men (MSM) is one of the major challenges facing China. However, the overall burden is still not clear. This study aims to summarize the incidence of syphilis among MSM in China by using meta-analysis. We comprehensively searched PubMed-MEDLINE, China National Knowledge Infrastructure and Chinese Wanfang databases. Articles published between December 2009 and March 2015 that met the inclusion criteria were considerably involved in this meta-analysis. Two reviewers performed a quality assessment of the studies and extracted data for estimating the overall syphilis incidence. STATA 12.0 was used to summarize the overall incidence of syphilis. In all, 14 studies from 13 papers were included in this study. Follow up duration of these studies ranged from six to 36 months, while drop-out rates ranged from 11.9% to 83.6%. The individual incidence rates of the included studies varied from 3.1/100 person-years (95% CI, 0.8-5.3/100 person-years) to 38.5/100 person-years (95% CI, 28.9-48.1/100 person-years), with a pooled incidence of 9.6/100 person-years (95% CI, 7.0-12.2/100 person-years). The subgroup meta-analysis revealed that incidence estimates were 38.5/100 person years (95% CI, 28.9-48.1/100 person-years), 12.1/100 person-years (95% CI, 7.0 17.2/100 person-years), 11.2/100 person-years (95% CI, 0.7-23.1/100 person years), 8.9/100 person-years (95% CI, 6.5-11.2/100 person-years), 5.7/100 person years (95% CI, 3.4-8.0/100 person-years) and 3.1/100 person-years (95% CI, 0.8 5.3/100 person-years) in Northeast, North, Southwest, East, South and Northwest China, respectively. Syphilis incidence among Chinese MSM is high, and this may increase the spread of other sexually transmitted infections, including human immunodeficiency virus. It is essential to integrate syphilis control programs with HIV control programs. This can be achieved by establishing public health response systems to monitor and control the epidemic of syphilis and HIV together in China. PMID- 26992413 TI - Ambulatory Blood Pressure Parameters and Heart Failure With Reduced or Preserved Ejection Fraction in Elderly Treated Hypertensive Patients. AB - BACKGROUND: The association between ambulatory blood pressure (BP) and future risk of heart failure (HF) is unclear. We investigated the association between ambulatory BP parameters and risk of HF with reduced ejection fraction (HFREF) or preserved ejection fraction (HFPEF) in elderly treated hypertensive patients. METHODS: The occurrence of HFREF and HFPEF was evaluated in 1,191 elderly treated hypertensive patients who underwent clinical and instrumental evaluation, including ambulatory BP monitoring to evaluate daytime, nighttime, and 24-hour BP, dipping status, and morning surge (MS) of BP. RESULTS: During the follow-up (9.1+/-4.9 years, range 0.4-20 years), 123 patients developed HF, of whom 56 had HFREF and 67 had HFPEF. After adjustment for other covariates, Cox regression analysis showed that 24-hour systolic BP, but not clinic BP, was independently associated with risk of both HFREF (hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.14-1.63, per 10mm Hg increment) and HFPEF (HR: 1.35, 95% CI: 1.13-1.61, per 10mm Hg increment); moreover, high MS of BP (>23mm Hg) in dippers was independently associated with risk of HFREF (HR: 2.27, 95% CI: 1.00-5.15) and nondipping was independently associated with risk of HFPEF (HR: 2.78, 95% CI: 1.38-5.63). CONCLUSIONS: In elderly treated hypertensive patients, 24-hour systolic BP is independently associated with future risk of both HFREF and HFPEF, whereas high MS is independently associated with risk of HFREF and nondipping is independently associated with risk of HFPEF. PMID- 26992414 TI - People with autism die 16 years earlier on average, says charity. PMID- 26992415 TI - Treatment of symptomatic non-unions of the base of the ulnar styloid with plate osteosynthesis. AB - : The purpose of this prospective case series was to assess the efficacy of plate osteosynthesis using a low profile distal ulna plate for the management of persistently symptomatic non-unions of the base of the ulnar styloid. Six consecutive patients underwent resection of the non-union and plate osteosynthesis with a 2.0 mm distal ulna hook plate. Post-operative measurements of mean pain scores, QuickDASH scores, grip strength, and range of motion parameters showed significant improvements compared with the pre-operative values. No complications were reported at a mean follow-up of 25 months. The present study presents an alternative method for treating symptomatic ulnar styloid non-unions that provides stable fixation with low risk of implant removal. LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26992416 TI - The Anolis Lizard Genome: An Amniote Genome without Isochores? AB - Two articles published 5 years ago concluded that the genome of the lizard Anolis carolinensis is an amniote genome without isochores. This claim was apparently contradicting previous results on the general presence of an isochore organization in all vertebrate genomes tested (including Anolis). In this investigation, we demonstrate that the Anolis genome is indeed heterogeneous in base composition, since its macrochromosomes comprise isochores mainly from the L2 and H1 families (a moderately GC-poor and a moderately GC-rich family, respectively), and since the majority of the sequenced microchromosomes consists of H1 isochores. These families are associated with different features of genome structure, including gene density and compositional correlations (e.g., GC3 vs flanking sequence GC and intron GC), as in the case of mammalian and avian genomes. Moreover, the assembled Anolis chromosomes have an enormous number of gaps, which could be due to sequencing problems in GC-rich regions of the genome. In conclusion, the Anolis genome is no exception to the general rule of an isochore organization in the genomes of vertebrates (and other eukaryotes). PMID- 26992417 TI - Transformative therapy in hypophosphatasia. PMID- 26992420 TI - Safety of optical coherence tomography in daily practice: a comparison with intravascular ultrasound. AB - Aims: Previous studies have reported the safety and feasibility of both time domain optical coherence tomography (TD-OCT) and Fourier-domain OCT (FD-OCT) in highly selected patients and clinical settings. However, the generalizability of these data is limited, and data in unselected patient populations reflecting a routine cathlab practice are lacking. We compared safety of intracoronary FD-OCT imaging to intravascular ultrasound (IVUS) imaging in a large real-world series of consecutive patients who underwent invasive imaging during coronary catheterization in our centre. Methods and results: This is a prospective, single centre registry of patients scheduled for coronary angiography or intervention undergoing intracoronary imaging with FD-OCT or IVUS between April 2008 and December 2013. Intra-procedural and major in-hospital adverse events that could be possibly related to invasive imaging were registered routinely by the operator as part of our clinical report and prospectively recorded in our database. These events were retrospectively individually adjudicated by an independent safety committee. Between April 2008 and December 2013, 13 418 diagnostic or interventional coronary catheterization procedures were performed. Of these, 1142 procedures used OCT and 2476 procedures used IVUS. Invasive imaging-related complications were rare, did not differ between the two imaging methods (OCT: n = 7, 0.6%; IVUS: n = 12, 0.5%; P = 0.6), and were self-limiting after retrieval of the imaging catheter or easily treatable in the catheterization laboratory. No major adverse events, prolongation of hospital stay, or permanent patient harm was observed. Conclusion: FD-OCT is safe in an unselected and heterogeneous group of patients with varying clinical settings. PMID- 26992418 TI - A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine. AB - Monoclonal gammopathy is increasingly recognized as a cause of kidney injury. These renal conditions behave differently than ones without monoclonal gammopathy and require specific treatment. To avoid misdiagnosis, testing for paraprotein should be performed in addition to vasculitis and autoimmune diseases serologies in adults with unexplained AKI or proteinuria. Because the prevalence of monoclonal gammopathy is much more common than glomerular diseases, the nephrotoxicity of the monoclonal protein must be confirmed before cytotoxic therapy is initiated. This can only be done by a kidney biopsy. After a monoclonal gammopathy of renal significant is verified, the evaluation should then focus on the identification of the pathologic clone, because therapy is clone specific. We present this patient to illustrate the clinical presentation of a patient with renal dysfunction and a monoclonal gammopathy. This patient is also used to discuss the diagnostic process in detail when monoclonal gammopathy associated renal disease is suspected. PMID- 26992421 TI - Acral Hemorrhagic Darier's Disease: A Case Report. AB - BACKGROUND: Darier's disease is an autosomal-dominant inherited disorder with pathogenic changes of keratinization with various forms of cutaneous phenotypes. Rare forms of Darier's disease are uncommonly seen. METHODS: The investigators report the case of a 65-year-old woman who presented with hemorrhagic vesicles on the dorsum of her hands. She had no history of any previous skin disorder. There was no family history of any skin disorder. RESULTS: A biopsy supported a diagnosis of acral hemorrhagic Darier's disease. The patient was treated with topical retinoids, and her condition improved. CONCLUSION: Acral hemorrhagic Darier's disease is rarely reported in the literature. PMID- 26992419 TI - Multicentre multi-device hybrid imaging study of coronary artery disease: results from the EValuation of INtegrated Cardiac Imaging for the Detection and Characterization of Ischaemic Heart Disease (EVINCI) hybrid imaging population. AB - AIMS: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting. METHODS AND RESULTS: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR<=0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively. CONCLUSION: In patients at intermediate risk of CAD, hybrid imaging allows non invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects. PMID- 26992422 TI - Psoronychomycosis: A New Term for an Old Problem. AB - Occasionally, psoriatic nail changes are seen in psoriatic patients. The prevalence of psoriasis of the nails has been reported to range from 15% to 79%. Even with effective systemic treatment for psoriasis, the nails may not improve, and these nails are considered nonresponsive psoriatic nails. Psoriatic nails are rarely investigated, and it is assumed that the nail changes are simply attributed to psoriasis because of their clinical similarity. Even patients with nails unresponsive to systemic treatment, or psoriasis treated topically or with phototherapy, onychomycosis is often forgotten, and patients may be left with both onychomycosis and psoriasis or onychomycosis alone. A retrospective chart review of 361 patients was carried out. The investigators report the prevalence of psoriasis and onychomycosis as less than 1%. A new term, "psoronychomycosis," is suggested to denote the rare combination of psoriasis and onychomycosis. PMID- 26992423 TI - REG3beta Plays a Key Role in IL17RA Protumoral Effect-Letter. PMID- 26992424 TI - Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype. AB - Hypoxia is a common feature of solid tumors and is associated with aggressiveness and poor patient outcomes. Exosomes, initially considered to be cellular "garbage dumpsters," are now implicated in mediating interactions with the cellular environment. However, the mechanisms underlying the association between exosomes and hypoxia during cancer progression remain poorly understood. In this study, we found that exosomes derived from hypoxic oral squamous cell carcinoma (OSCC) cells increased the migration and invasion of OSCC cells in a HIF-1alpha and HIF 2alpha-dependent manner. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we performed miRNA sequencing of normoxic and hypoxic OSCC-derived exosomes. Of the 108 miRNAs that were differentially expressed, miR-21 stood out as one of the most significantly upregulated miRNAs under hypoxic conditions. miR-21 depletion in hypoxic OSCC cells led to decreased miR-21 levels in exosomes and significantly reduced cell migration and invasion. Conversely, restoration of miR-21 expression in HIF-1alpha and HIF-2alpha depleted exosomes rescued OSCC cell migration and invasion. Moreover, exosomal miR-21 markedly enhanced snail and vimentin expression, while significantly decreasing E-cadherin levels in OSCC cells, in vitro and in vivo Finally, circulating exosomal miR-21 levels were closely associated with HIF-1alpha/HIF 2alpha expression, T stage, and lymph node metastasis in patients with OSCC. In conclusion, our findings suggest that the hypoxic microenvironment may stimulate tumor cells to generate miR-21-rich exosomes that are delivered to normoxic cells to promote prometastatic behaviors and prompt further investigation into the therapeutic value of exosome inhibition for cancer treatment. Cancer Res; 76(7); 1770-80. (c)2016 AACR. PMID- 26992425 TI - REG3beta Plays a Key Role in IL17RA Protumoral Effect-Response. PMID- 26992428 TI - Hepatic-specific PPARalpha-FGF21 action in NAFLD. PMID- 26992426 TI - Tumour-associated and non-tumour-associated microbiota in colorectal cancer. AB - OBJECTIVE: A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. DESIGN: We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples ('ON' and 'OFF' the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. RESULTS: The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. CONCLUSIONS: CRC associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers. PMID- 26992429 TI - HIV-1 gp120 signaling through TLR4 modulates innate immune activation in human macrophages and the biology of hepatic stellate cells. AB - Highly active antiretroviral therapy has significantly improved the prognosis of HIV-infected subjects. However, patients treated long term still manifest increased mortality and, even with undetectable plasma viremia, often experience persistent immune activation. Furthermore, liver-related mortality is now the most common cause of non-AIDS-related death in HIV-infected individuals on highly active antiretroviral therapy through accelerated fibrosis progression. TLRs are the first line of the host response to pathogens and play an important role in human host defense against viruses through sensing of viral structural proteins. Growing evidence points to TLR4 as a key player in chronic immune activation, HIV recognition/replication, and liver fibrosis progression, suggesting that HIV triggering of TLR4 may dictate some aspects of the multifaceted AIDS pathogenesis. In this study, we provide evidence for an interplay between host TLR4 and HIV-1 gp120 in human monocyte-derived macrophages and hepatic stellate cells, leading to intracellular pathways and biologic activities that mediate proinflammatory and profibrogenic signals. Finally, we hypothesize that CCR5 and TLR4 are likely part of a common receptor cluster, as the blocking of CCR5 by specific antagonists impairs the macrophage capacity to produce chemokines in response to LPS. Chronic immune activation and liver fibrosis remain important obstacles for highly active antiretroviral therapy success. Thus, the identification of gp120-TLR4 axis as a novel determinant of immune system and hepatic stellate cell biology opens new perspectives to the management of HIV infection and disease. PMID- 26992430 TI - Flagellin preconditioning enhances the efficacy of mesenchymal stem cells in an irradiation-induced proctitis model. AB - The success of mesenchymal stem cell transplantation for proctitis depends not only on cell donors but also on host microenvironmental factors, which play a major role in conditioning mesenchymal stem cell immunosuppressive action and repair. This study sought to determine if flagellin, a TLR5 ligand, can enhance the mesenchymal stem cell treatment efficacy in radiation-induced proctitis. With the use of a colorectal model of 27 Gy irradiation in rats, we investigated and compared the effects on immune capacity and remodeling at 28 d after irradiation of the following: 1) systemic mesenchymal stem cell (5 * 10(6)) administration at d 7 after irradiation, 2) administration of flagellin at d 3 and systemic mesenchymal stem cell administration at d 7, and 3) in vitro preconditioning of mesenchymal stem cells with flagellin, 24 h before their administration on d 7. The mucosal CD8(+) T cell population was normalized after treatment with flagellin-preconditioned mesenchymal stem cells or flagellin plus mesenchymal stem cells, whereas mesenchymal stem cells alone did not alter the radiation induced elevation of CD8(+) T cell frequency. Mesenchymal stem cell treatment returned the irradiation-elevated frequency of CD25(+) cells in the mucosa-to control levels, whereas both flagellin-preconditioned mesenchymal stem cell and flagellin-plus-mesenchymal stem cell treatment each significantly increased not only CD25(+) cell frequency but also forkhead box p3 and IL-2Ralpha expression. Specifically, IL-10 was overexpressed after flagellin-preconditioned mesenchymal stem cell treatment. Analysis of collagen expression showed that the collagen type 1/collagen type 3 ratio, an indicator of wound-healing maturation, was low in the irradiated and mesenchymal stem cell-treated groups and returned to the normal level only after the flagellin-preconditioned mesenchymal stem cell treatment. This was associated with a reduction in myofibroblast accumulation. In a proctitis model, flagellin-preconditioned mesenchymal stem cells improved colonic immune capacity and enhanced tissue remodeling. PMID- 26992431 TI - CCL2 expression is mediated by type I IFN receptor and recruits NK and T cells to the lung during MVA infection. AB - Migration of leukocytes to the site of microbial infection is important for the development of effective host immunity. Recombinant modified vaccinia virus Ankara is frequently used as a viral vector vaccine in preclinical and clinical studies. In comparison to other vaccinia virus strains, modified vaccinia virus Ankara robustly induces chemokine expression and rapid attraction of leukocytes. In particular, chemokine (C-C motif) ligand 2 (CCL2) has been shown to be critical for leukocyte recruitment to the lung. In this study, MVA-induced CCL2 expression in murine macrophages was dependent on type I interferon receptor and not Toll-like receptor-2. The critical role of type I interferon receptor signaling for CCL2 production in the lung was confirmed in type I interferon receptor-deficient mice (Ifnar1(-/-)). In addition, comparing Ifnar1(-/-) and Ccl2(-/-) mice with wild-type mice, we observed a similar impairment in the recruitment of natural killer and T cells to the lung after intranasal infection with modified vaccinia virus Ankara. Conversely, neutrophil recruitment was not affected in Ifnar1(-/-) and Ccl2(-/-) mice. We conclude that type I interferons, besides their known antiviral properties, can initiate the recruitment and activation of leukocytes via induction of chemokine expression including CCL2. PMID- 26992432 TI - Neutrophil extracellular trap formation is elicited in response to cold physical plasma. AB - Cold physical plasma is an ionized gas with a multitude of components, including hydrogen peroxide and other reactive oxygen and nitrogen species. Recent studies suggest that exposure of wounds to cold plasma may accelerate healing. Upon wounding, neutrophils are the first line of defense against invading microorganisms but have also been identified to play a role in delayed healing. In this study, we examined how plasma treatment affects the functions of peripheral blood neutrophils. Plasma treatment induced oxidative stress, as assessed by the oxidation of intracellular fluorescent redox probes; reduced metabolic activity; but did not induce early apoptosis. Neutrophil oxidative burst was only modestly affected after plasma treatment, and the killing of Pseudomonas aeruginosa and Staphylococcus aureus was not significantly affected. Intriguingly, we found that plasma induced profound extracellular trap formation. This was inhibited by the presence of catalase during plasma treatment but was not replicated by adding an equivalent concentration of hydrogen peroxide. Plasma induced neutrophil extracellular trap formation was not dependent on the activity of myeloperoxidase or NADPH oxidase 2 but seemed to involve short-lived molecules. The amount of DNA release and the time course after plasma treatment were similar to that with the common neutrophil extracellular trap inducer PMA. After neutrophil extracellular traps had formed, concentrations of IL-8 were also significantly increased in supernatants of plasma-treated neutrophils. Both neutrophil extracellular traps and IL-8 release may aid antimicrobial activity and spur inflammation at the wound site. Whether this aids or exacerbates wound healing needs to be tested. PMID- 26992433 TI - Perturbed MafB/GATA1 axis after burn trauma bares the potential mechanism for immune suppression and anemia of critical illness. AB - Patients who survive initial burn injury are susceptible to nosocomial infections. Anemia of critical illness is a compounding factor in burn patients that necessitates repeated transfusions, which further increase their susceptibility to infections and sepsis. Robust host response is dependent on an adequate number and function of monocytes/macrophages and dendritic cells. In addition to impaired RBC production, burn patients are prone to depletion of dendritic cells and an increase in deactivated monocytes. In steady-state hematopoiesis, RBCs, macrophages, and dendritic cells are all generated from a common myeloid progenitor within the bone marrow. We hypothesized in a mouse model of burn injury that an increase in myeloid-specific transcription factor V maf musculoaponeurotic fibrosarcoma oncogene homolog B at the common myeloid progenitor stage steers their lineage potential away from the megakaryocyte erythrocyte progenitor production and drives the terminal fate of common myeloid progenitors to form macrophages vs. dendritic cells, with the consequences being anemia, monocytosis, and dendritic cell deficits. Results indicate that, even though burn injury stimulated bone marrow hematopoiesis by increasing multipotential stem cell production (LinnegSca1poscKitpos), the bone marrow commitment is shifted away from the megakaryocyte erythrocyte progenitor and toward granulocyte monocyte progenitors with corresponding alterations in peripheral blood components, such as hemoglobin, hematocrit, RBCs, monocytes, and granulocytes. Furthermore, burn-induced V-maf musculoaponeurotic fibrosarcoma oncogene homolog B in common myeloid progenitors acts as a transcriptional activator of M-CSFR and a repressor of transferrin receptors, promoting macrophages and inhibiting erythroid differentiations while dictating a plasmacytoid dendritic cell phenotype. Results from small interfering RNA and gain-of-function (gfp-globin transcription factor 1 retrovirus) studies indicate that targeted interventions to restore V-maf musculoaponeurotic fibrosarcoma oncogene homolog B/globin transcription factor 1 balance can mitigate both immune imbalance and anemia of critical illness. PMID- 26992434 TI - Hypoxia-inducible factor-2alpha promotes hepatocyte apoptosis during cholestasis. AB - AIM: Hypoxia-inducible factor-2alpha (HIF-2alpha) has been reported to play an important role in a host of pathophysiological processes, including cellular survival. This study explores the role of HIF-2alpha in cholestasis-mediated hepatocyte apoptosis. METHODS: Hypoxia-inducible factor-2alpha expression was measured by immunohistochemistry and confocal microscopy. Hepatic apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling. The cholestatic mouse model was treated with bile duct ligation. The c-myc, p53, and Bax protein levels were measured with Western blot analysis. RESULTS: In pediatric and murine cholestatic liver tissues, HIF-2alpha protein was widely expressed in the nucleus of parenchymal cells as well as in stromal cells. Hepatocyte HIF-2alpha expression was significantly elevated at the early stage of pediatric cholestasis and decreased at the late stage. In both in vivo and in vitro murine studies, HIF-2alpha deletion could alleviate cholestasis mediated hepatocyte apoptosis and regulate the expression of c-myc, p53, and Bax proteins. CONCLUSION: These findings implied the contribution of HIF-2alpha to cholestasis-mediated hepatocyte apoptosis. PMID- 26992436 TI - Response to "Hair 'regrowth' during chemotherapy after scalp cooling technique". PMID- 26992437 TI - Helical Inversion of Gel Fibrils by Elongation of Perfluoroalkyl Chains as Studied by Vibrational Circular Dichroism. AB - Vibrational circular dichroism (VCD) spectroscopy was applied to gelation by a chiral low-molecular mass weight gelator, N,N'-diperfluoroalkanoyl-1,2-trans diaminocyclohexane. Attention was focused on the winding effects of (-CF2 )n chains on the gelating ability. For this purpose, a series of gelators were synthesized with perfluoroalkyl chains of different length (n = 6-8). When gelation was studied using acetonitrile as a solvent, the fibrils took different morphologies, depending on the chain length: twisted saddle-like ribbon or helical ribbon from fibril (n = 6) and a helical ribbon from platelet (n = 8). The signs of VCD peaks assigned to the couplet of C=O stretching and to the C-F stretching were also dependent on n, indicating that a gelator molecule changed conformation on elongating perfluoroalkyl chains. A model is proposed for the aggregation modes in fibrils. Chirality 28:361-364, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26992438 TI - N-dimensional switch function for energy conservation in multiprocess reaction dynamics. AB - The MReaDy program was designed for studying Multiprocess Reactive Dynamic systems, that is, complex chemical systems involving different and concurrent reactions. It builds a global potential energy surface integrating a variety of potential energy surfaces, each one of them representing an elementary reaction expected to play a role in the chemical process. For each elementary reaction, energy continuity problems may happen in the transition between potential energy surfaces due to differences in the functional form for each of the fragments, especially if built by different authors. A N-dimensional switch function is introduced in MReaDy in order to overcome such a problem. As an example, results of a collision trajectory calculation for H2 + OH -> H3 O are presented, showing smooth transition in the potential energy, leading to conservation in the total energy. Calculations for a hydrogen combustion system from 1000 K up to 4000 K shows a variation of 0.012% when compared to the total energy of the system. (c) 2016 Wiley Periodicals, Inc. PMID- 26992435 TI - Blood lipids and prostate cancer: a Mendelian randomization analysis. AB - Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (>=7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy. PMID- 26992439 TI - Influence of maintenance care in periodontally susceptible and non-susceptible subjects following implant therapy. AB - OBJECTIVES: To compare the periodontal and peri-implant conditions of periodontally susceptible and periodontally healthy subjects under maintenance care for a period of at least 3 years. MATERIAL AND METHODS: Sixty periodontally susceptible patients (PSP) and 56 periodontally non-susceptible subjects (PHS) were treated with dental implants in the National Dental Centre Singapore (NDCS) and were maintained in a regular supportive periodontal care program for a mean of 6 years. Full mouth bleeding on probing (BoP), full mouth probing pocket depths (PPD), implant loss, and absence of crestal bone loss were recorded at the time of prosthesis delivery and following a mean follow-up of 6 years 2 months. RESULTS: Although there were significant differences in the BoP and the percentage of subjects with tooth probing pocket depth >=5 mm between PSP and PHS at the time of implant prosthesis installation (T0 ), there were no significant differences between the two subject groups in the various parameters assessed at the follow-up visit (T1 ) (total number of teeth, percentage of subjects with implant probing pocket depth >=5 mm, percentage of subjects with implant probing pocket depth >= 6 mm, absence of crestal bone loss, implant loss). CONCLUSION: Owing to a rigid regular SPT program, implants placed in PSP perform equally well when compared to implants installed in PHS over a mean period of 6-year follow up. PMID- 26992440 TI - Association of mean platelet volume and platelet count with the development and prognosis of ischemic and hemorrhagic stroke. AB - INTRODUCTION: Mean platelet volume (MPV) and platelet (PLT) count are the two major parameters that reflect the functions and activities of PLTs. The associations of MPV and PLT count with the occurrence and prognosis of stroke have not been fully clarified. This study aimed to investigate the association of MPV and PLT count with the development and prognosis of first-ever ischemic and hemorrhagic stroke in order to provide evidence for early diagnosis and treatment of both strokes. METHODS: This study included 281 first-ever ischemic stroke and 164 first-ever hemorrhagic stroke patients between 2010 and 2012. All participants received routine blood tests within 2 h after admission and were categorized into good or poor prognosis group based on the Modified Rankin Scale (mRS) score. MPV and PLT counts were transformed into categorical variables and their association with the occurrence and prognosis of both strokes was evaluated by multivariate logistic regression. RESULTS: The risk of ischemic and hemorrhagic stroke in MPV group (>13 fL) was 22.17 and 5.21 times higher compared with normal MPV group. The PLT count was positively correlated with the risk of ischemic stroke, but negatively correlated with the risk of hemorrhagic stroke. MPV and PLT count was not correlated with the prognosis of either stroke. CONCLUSIONS: Increased MPV is an independent risk factor for both strokes. Elevated PLT count increases the risk for ischemic stroke, but decreases the risk for hemorrhagic stroke. However, neither MPV nor PLT count has significant association with the prognosis of either stroke. PMID- 26992442 TI - Detection of human papillomavirus type 124 in a viral wart located on a thigh. PMID- 26992441 TI - Timing of primary tooth emergence among U.S. racial and ethnic groups. AB - OBJECTIVES: To compare timing of tooth emergence among groups of American Indian (AI), Black and White children in the United States at 12 months of age. METHODS: Data were from two sources - a longitudinal study of a Northern Plains tribal community and a study with sites in Indiana, Iowa and North Carolina. For the Northern Plains study, all children (n = 223) were American Indian, while for the multisite study, children (n = 320) were from diverse racial groups. Analyses were limited to data from examinations conducted within 30 days of the child's first birthday. RESULTS: AI children had significantly more teeth present (Mean: 7.8, Median: 8.0) than did Whites (4.4, 4.0, P < 0.001) or Blacks (4.5, 4.0, P < 0.001). No significant differences were detected between Black and White children (P = 0.58). There was no significant sex difference overall or within any of the racial groups. CONCLUSIONS: Tooth emergence occurs at a younger age for AI children than it does for contemporary White or Black children in the United States. PMID- 26992443 TI - Asymmetric dimethylarginine (ADMA) treatment induces apoptosis in cultured rat mesangial cells via endoplasmic reticulum stress activation. AB - Asymmetric dimethylarginine (ADMA), a high risk factor for endothelial dysfunction and cardiovascular disease (CVD), has been reported to promote cellular dysfunction via endoplasmic reticulum (ER) stress activation in various cells. Additionally, increased serum ADMA levels have been observed in incipient kidney diseases. Previously, we reported that activated ER stress is associated with mesangial cell apoptosis, observed mainly in overt nephropathy or chronic kidney disease (CKD). However, the effect of ADMA on mesangial cell apoptosis is unknown. Thus, we investigated the effects of ADMA on mesangial cell apoptosis and ER stress signaling. ADMA treatment increased caspase-3 activity and activated three branches of ER stress signaling (PERK, IRE1, and ATF6) that induce mesangial cell apoptosis. Pharmacological inhibitors of ER stress (inhibitors of PERK, IRE1, and S1P) attenuated ADMA-induced cleavage of caspase-3 and induced a decrease in the mitochondrial membrane potential. Furthermore, these inhibitors diminished the number of apoptotic cells induced by ADMA treatment. Taken together, our results indicated that ADMA treatment induces mesangial cell apoptosis via ER stress signaling. These results suggest that ADMA induced mesangial cell apoptosis could contribute to the progression of overt nephropathy and CKD. PMID- 26992444 TI - The controversy over the use of cholesteryl ester transfer protein inhibitors: is there some light at the end of the tunnel? AB - BACKGROUND: According to epidemiological studies, there is no clear relationship between the plasma cholesteryl ester transfer protein (CETP) concentration and the development of atherosclerosis in human populations. Although some studies suggest that increased CETP activity relates to undesirable profiles of plasma lipoproteins, promoting an anti-atherogenic plasma lipoprotein profile by drugs that inhibit CETP has not succeeded in preventing atherosclerosis in humans. MATERIALS AND METHODS: This review describes 28 investigations in human populations dealing with plasma CETP, 11 in mice that express human CETP and seven in animals (six in rabbits and one in mice) in which plasma CETP activity was inhibited by drugs. RESULTS: Present review shows that models in mice expressing human CETP are not illuminating because they report increase as well reduction of atherosclerosis. However, investigations in rabbits and mice that develop severe hypercholesterolaemia clearly indicate that impairment of the plasma CETP activity elicits protection against the development of atherosclerosis; in all of these experiments are attained substantial reductions of the atherogenic lipoproteins, namely, plasma apoB containing lipoproteins. CONCLUSION: These models are strong indicators that the benefit in preventing atherosclerosis should be earned in cases of hyperlipidemia by CETP inhibitors. PMID- 26992445 TI - Mammary tumor growth and metastasis are reduced in c-Kit mutant Sash mice. AB - Besides its well-known function in allergic response, mast cell, one of the key immune cells present in tumor microenvironment, plays important roles in cancer progression. However, the functional role of mast cells in breast cancer development and metastasis is not well understood. To test the involvement of mast cells in breast cancer, we examined the effects of loss of mast cells on mammary tumor development by crossing the well-known mast cell deficient mouse strain sash (Kit(W-sh/W-sh) ) with the mammary tumor transgenic mouse strain MMTV Polyoma Middle T antigen (PyMT). Although mammary tumor onset was not affected in the absence of mast cells, mammary growth and metastasis were reduced in PyMT/Kit(W-sh/W-sh) mice compared with PyMT/wild-type mice (WT). Histological and immunofluorescent analyses showed that tumors from PyMT/Kit(W-sh/W-sh) mice showed largely differentiated morphology with reduced angiogenesis compared with MMTV-PyMT/WT mice. Our results suggest that mast cells may promote breast cancer growth and metastasis. Agents that can block mast cells growth are potential new therapies to treat metastatic breast cancer. PMID- 26992446 TI - Non-alcoholic steatohepatitis-associated hepatic fibrosis and hepatocellular carcinoma in a combined mouse model of genetic modification and dietary challenge. AB - AIM: Experimental models of non-alcoholic steatohepatitis (NASH) are still required for understanding the pathophysiology of this disease. This study aimed to examine whether disease progression is accelerated by combining dyslipidemic genetic modification and dietary challenges and develop NASH-associated hepatic fibrosis, cirrhosis, and carcinoma in a short period. METHODS: Low-density lipoprotein receptor knockout mice were fed a modified choline-deficient amino acid-defined diet, including 1 w/w% cholesterol and 41 kcal% fat, and was comprehensively profiled over 1 year. RESULTS: Microvesicular and macrovesicular steatosis in the liver was observed from the first week after starting the modified choline-deficient amino acid-defined diet. Macrovesicular steatosis was exacerbated with time and was observed in almost all hepatocytes at week 8, but slightly decreased at week 16. Infiltration of macrophages and neutrophils, and upregulation of hepatic inflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta were also observed from week 1. Plasma hepatic transaminase activities were increased at week 1, reached a peak at week 4, and gradually decreased thereafter. In parallel with increases in hepatic gene expression of collagen-I, the hepatic fibrosis area expanded after week 4 and massively spread all over the liver by week 8. Hepatocellular hyperplasia was observed from week 24. Hepatocellular adenoma and carcinoma were observed from week 31 and 39, respectively. CONCLUSION: These results suggest that, in a rodent NASH model with the combination of genetic modification and dietary challenges, hepatic steatosis, inflammatory cell infiltration and hepatic injury, hepatic fibrosis, hepatocellular hyperplasia, adenoma, and carcinoma can be developed in a relatively short period. PMID- 26992447 TI - Quantum monte carlo study of the energetics of small hydrogenated and fluoride lithium clusters. AB - An investigation of the energetics of small lithium clusters doped either with a hydrogen or with a fluorine atom as a function of the number of lithium atoms using fixed-node diffusion quantum Monte Carlo (DMC) simulation is reported. It is found that the binding energy (BE) for the doped clusters increases in absolute values leading to a more stable system than for the pure ones in excellent agreement with available experimental measurements. The BE increases for pure, remains almost constant for hydrogenated, and decreases rapidly toward the bulk lithium for the fluoride as a function of the number of lithium atoms in the clusters. The BE, dissociation energy as well as the second difference in energy display a pronounced odd-even oscillation with the number of lithium atoms. The electron correlation inverts the odd-even oscillation pattern for the doped in comparison with the pure clusters and has an impact of 29%-83% to the BE being higher in the pure cluster followed by the hydrogenated and then by the fluoride. The dissociation energy and the second difference in energy indicate that the doped cluster Li3 H is the most stable whereas among the pure ones the more stable are Li2 , Li4 , and Li6 . The electron correlation energy is crucial for the stabilization of Li3 H. (c) 2016 Wiley Periodicals, Inc. PMID- 26992448 TI - Enantiomeric Separation of Chiral Pesticides by Permethylated beta-Cyclodextrin Stationary Phase in Reversed Phase Liquid Chromatography. AB - Enantiomeric separation of six chiral pesticides by high-performance liquid chromatography with permethylated beta-cyclodextrin (beta-PM) chiral stationary phase were tested under reversed phase conditions. The influences of water composition from 10% to 45% in the mobile phase and column temperatures from 0 degrees C to 40 degrees C on the separation were investigated. Baseline separation was obtained for diclofop-methyl, fenoxaprop-ethyl, tebuconazole and triticonazole, and Rs of these pesticides were greater than 1.5. However, etoxazole and lactofen were partially separated in all experiments. PMID- 26992449 TI - Comparison of growth & function of endothelial progenitor cells cultured on deproteinized bovine bone modified with covalently bound fibronectin and bound vascular endothelial growth factor. AB - OBJECTIVES: The objective of this study was to assess and compare the growth and function of Endothelial Progenitor Cells (EPCs) cultured on covalently bonded Vascular Endothelial Growth Factor (VEGF) and covalently bonded Fibronectin (FN) coating on deproteinized bovine bone (DBB) (test samples), compared to non modified DBB blocks (control sample). MATERIALS AND METHODS: The test samples were prepared by plasma polymerization of allylamine onto DBB blocks. Group1 of test samples were prepared with VEGF coating (VEGF-DBB) where as the Group2 test samples were coated with FN (FN-DBB). Non-modified DBB blocks served as a Control. EPCs were isolated and cultivated from buffy coats of peripheral blood of healthy volunteers and cultivated in the different samples and examined at time intervals of 24 h, 3 days, and 7 days. Evaluation of growth by cell count and cell morphology was done using Confocal Laser Scanning Electron Microscopy; vitality and function of cells was assessed using MTT assay and RT-PCR and ELISA for eNOS and iNOS respectively. RESULTS: The results of the study show that both VEGF and FN could be successfully immobilized by plasma polymerization onto a complex, porous, three-dimensional structure of DBB. When comparing vital cell coverage, proliferation and function of EPCs, FN-DBB provided more positive values followed by VEGF-DBB as compared to DBB samples. eNOS level were significant higher in VEGF-DBB and FN-DBB when compared to DBB (P = 0.019 and P = 0.002). The difference between VEGF-DBB and FN-DBB was not significant. CONCLUSIONS: Biomimetic coatings of Fibronectin may clinically relate to faster angiogenesis and earlier healing potential. PMID- 26992450 TI - Epidemiological analysis of psoriatic arthritis patients in Japan. AB - To determine the current status of psoriatic arthritis, we conducted a retrospective survey by sending questionnaires. The newly visited psoriatic arthritis patients accounted for 10.5% (95% confidence interval, 7.9-13%) of all newly visited psoriasis patients (n = 2581) between April 2014 and March 2015 in 73 institutes. Additionally, questionnaires on detailed patients' information were returned by 92 institutes (response rate, 70.8%), where 1282 patients with psoriatic arthritis were identified. There was a male predominance. The mean onset age of psoriatic arthritis was 44.9 years, and mean onset age for cutaneous psoriasis (36.4 years) was lower than that for arthritis (45.1 years). The mean duration in patients who developed psoriasis prior to arthritis was 11.2 years, while that in patients preceded by arthritis was 4.4 years. According to the Moll and Wright criteria, polyarthritis type was most common (36%), followed by distal interphalangeal type (26%) and oligoarthritis type (22%). Peripheral joint pain was 61.5%, back pain such as lumbago and neck pain was 34.3%. Enthesitis and dactylitis were observed in 28.3% and 59.2%, respectively. Biologics were used in 55.5% of psoriatic arthritis patients, and 31% used disease-modifying antirheumatic drugs. In conclusion, the ratio of psoriatic arthritis in Japan is increasing, and nearly 10% of new psoriasis patients had psoriatic arthritis. This study shows the current status of psoriatic arthritis in Japan, including several unexpected findings such as male predominance, longer duration between the onset of cutaneous psoriasis and arthritis, and dominance of polyarthritis. PMID- 26992451 TI - Similar Microbial Consortia and Genes Are Involved in the Biodegradation of Benzalkonium Chlorides in Different Environments. AB - Benzalkonium chlorides (BACs) are emerging pollutants. Identification of microorganisms and the genes involved in the biodegradation of BACs is crucial for better understanding the fate of BACs in the environment and developing treatment strategies. Four microbial communities degrading BACs were developed from sewage (SEW), activated sludge (AS), soil (SOIL) and sea sediment (SEA) samples. According to 16S rRNA pyrosequencing and shotgun metagenome sequencing analyses, the most abundant species represented uncharacterized members of the Pseudomonas and Achromobacter genera. BAC biotransformation rates of the enriched microbial communities were 2.8, 3.2, 17.8, and 24.3 MUM hr(-1) for SEA, AS, SOIL, and SEW, respectively, and were positively correlated with the relative abundance of a particular Pseudomonas sp. strain, BIOMIG1. The strain BIOMIG1 mineralizes BACs at a rate up to 2.40 MUmol hr(-1) 10(-11) cells. Genomes of four BAC degrading and nondegrading BIOMIG1 phenotypes were sequenced and differentially compared with each other. As a result, a gene cluster encoding for transporters, an integrase and a dioxygenase were involved in BAC biotransformation. Our results suggest that BIOMIG1 plays a key role on the fate of BACs in the environment and genes, other than those reported to date, are involved in BAC biotransformation in various habitats. PMID- 26992452 TI - Ex vivo evaluation of four final irrigation protocols on the removal of hard tissue debris from the mesial root canal system of mandibular first molars. AB - AIM: To evaluate the efficacy of four final irrigation protocols on the reduction of hard-tissue debris accumulated within the mesial root canal system of mandibular first molars using micro-CT analysis. METHODOLOGY: Forty mesial roots of mandibular molars with a single and continuous isthmus connecting the mesiobuccal and mesiolingual canals (Vertucci's Type I configuration) were selected and scanned at a resolution of 8.6 MUm. Canals were enlarged sequentially using WaveOne Small and Primary instruments activated in reciprocating motion without intracanal irrigation to allow debris to accumulate within the mesial root canal system. Then, specimens were anatomically matched and distributed into four groups (n = 10), according to the final irrigation protocol: apical positive pressure (APP), passive ultrasonic irrigation (PUI), Self-adjusting File (SAF) and XP-endo Finisher (XPF). The final irrigation procedures were performed over 2 min using a total of 5.5 mL of 2.5% NaOCl per canal. Reconstructed data sets were coregistered, and the mean percentage reduction of accumulated hard-tissue debris after the final irrigation procedures was compared statistically between groups using the anovapost hoc Tukey test with a significance level set at 5%. RESULTS: Reduction of accumulated hard-tissue debris was observed in all groups after the final irrigation protocol. Overall, PUI and XPF groups had higher mean percentage reductions of accumulated hard tissue debris (94.1% and 89.7%, respectively) than APP and SAF groups (45.7% and 41.3%, respectively) (P < 0.05). No significant differences were found when comparing the results of PUI and XPF groups (P > 0.05) or APP and SAF groups (P > 0.05). CONCLUSIONS: The PUI technique and XP-endo Finisher instrument were associated with significantly lower levels of AHTD compared with conventional irrigation and the modified SAF system protocol in mesial root canals of mandibular molars. PMID- 26992453 TI - Mesenchymal stem cells: From stem cells to sarcomas. AB - Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties-they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas. PMID- 26992454 TI - Local verification between the hematological analyzers Sysmex XN-series and XE 5000. AB - INTRODUCTION: The aim of this study was to perform a verification of the hematology analyzer Sysmex XN-2000 by comparing with the previous XE-5000. This study assessed the precision and carryover on the XN-2000 and the systematic error between the both counters according to desirable biological variability criterion and a flag comparison study. METHODS: Within-run precision and between batch precision were measured according to the ICSH guidelines. A comparative study was performed analyzing two hundred and six samples of peripheral blood from patients. The statistical study was conducted using the Passing-Bablok and Bland-Altman analyses. The leucocyte flag comparison was made by measuring the efficiency rate. RESULTS: Between-batch precision was lower than that recommended by the biological variability criterion and manufacturer specifications. The comparison gave nonagreement results for neutrophil and basophil counts according to the criterion of biological variability. Erythroblasts and immature granulocytes showed nonagreement, but there is no available biological variation database for these parameters to compare with. Nevertheless, excellent absolute agreement was found for red blood cell parameters, and for platelet, lymphocyte, monocyte, and eosinophil counts. CONCLUSIONS: The global results obtained for the precision, comparability, and efficiency provide a satisfactory integration of the XN-2000 in the core laboratory routine and accomplish an optimal reliability. PMID- 26992455 TI - Autoimmune hepatitis in a child presenting with hepatopulmonary syndrome (HPS). AB - HPS has been described in 9-20% of children with end-stage liver disease. We present a case of a previously, asymptomatic nine-yr-old incidentally found to have low oxygen saturation. Physical exam was remarkable for digital clubbing, splenomegaly and orthodeoxia. Laboratory evaluation revealed a low platelet count, hyperammonemia, and prolonged coagulation studies. Sonography showed evidence of splenomegaly and portal venous hypertension. High resolution CT thorax and CTA were normal. HPS was confirmed by agitated saline contrast enhanced echocardiography and Tc-99m MAA scan with evidence of intrapulmonary vascular dilatations. Liver biopsy was performed and consistent with autoimmune hepatitis. A high clinical index of suspicion should be maintained for HPS in pediatric patients who have unexplained hypoxemia as typical signs and symptoms of severe liver disease are often absent. In this report, we discuss a case of HPS complicated AIH in a pediatric patient and review the relevant literature. PMID- 26992457 TI - Dynamic changes of driver genes' mutations across clinical stages in nine cancer types. AB - The driver genes play critical roles for tumorigenesis, and the number of identified driver genes reached plateau. But how they act during different cancer development stages is lack of knowledge. We investigated 138 driver genes' mutation changes across clinical stages using 3,477 cases in nine cancer types from the Cancer Genome Atlas (TCGA) and constructed their temporal order relationships. We also examined the codon changes for the widely mutated TP53 and PIK3CA in tumor stages. Combinations of one to three driver genes specifically dominated in each cancer. Across the clinical stages, we categorized three patterns for the behaviors of driver genes' mutation changes in the nine cancer types: recurrently mutated in all the stages and triggering other mutations; certain mutations lost meanwhile other mutations emerged; mutations dominated across entire stages, while other mutations gradually appeared or disappeared. We observed different codon changes dominated in different stages and revealed mutations recurrently occurring on the hotspot regions of the coding sequence may be the core factor for driver genes' tumorigenesis. Our results highlighted the dynamic changes of oncogenesis roles in different clinical stages and suggested different diagnostic decision making according to the clinical stages of patients. PMID- 26992458 TI - Obstetric and long-term kidney outcomes in renal transplant recipients: a 40-yr single-center study. AB - Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case-cohort study was performed identifying 83 pairs of pregnant and non-pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre-eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of >=20% loss of eGFR between immediately pre-pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non-pregnant controls and a pregnancy was not associated with poorer 10-yr transplant or 20-yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long-term transplant function. PMID- 26992456 TI - Structure-activity relationship of the peptide binding-motif mediating the BRCA2:RAD51 protein-protein interaction. AB - RAD51 is a recombinase involved in the homologous recombination of double-strand breaks in DNA. RAD51 forms oligomers by binding to another molecule of RAD51 via an 'FxxA' motif, and the same recognition sequence is similarly utilised to bind BRCA2. We have tabulated the effects of mutation of this sequence, across a variety of experimental methods and from relevant mutations observed in the clinic. We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X-ray crystallography. Where possible, comparison between our tetrapeptide mutational study and the previously reported mutations is made, discrepancies are discussed and the importance of secondary structure in interpreting alanine scanning and mutational data of this nature is considered. PMID- 26992459 TI - Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck. AB - WHAT IS KNOWN AND OBJECTIVE: Heart failure remains a leading cause of morbidity and mortality worldwide. Advanced therapies have prolonged survival in patients with advanced heart failure, but pharmacotherapeutic optimization remains the mainstay of treatment. It has been over 10 years since the last mortality reducing medication has been approved by the Food and Drug Administration. This article reviews the background, current knowledge and data supporting the use of sacubitril/valsartan (Entresto((r)) ), the newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure. METHODS: A literature search was performed (January 1980 to August 2015) using PubMed and the search terms were as follows: neprilysin inhibitor, heart failure, endopeptidase, natriuretic peptides, angiotensin, omapatrilat, LCZ696, valsartan and sacubitril. Peer-reviewed, published clinical trials, review articles, relevant treatment guidelines and prescribing information documents were identified and reviewed for relevance. Additionally, reference citations from publications identified were reviewed. RESULTS AND DISCUSSION: The inhibition of endopeptidases has been an area of extensive study for the treatment of heart failure. Previously published literature with the endopeptidase inhibitor omapatrilat failed to demonstrate a sufficient balance between clinical efficacy and safety to justify its approval. Omapatrilat blocked three pathways that break down bradykinin, leading to high rates of angioedema. Sacubitril, on the other hand, is metabolized to a form that is highly selective for neprilysin without possessing activity for the other two peptidases, ACE and APP. The combination of sacubitril with valsartan in a single formulation offers the benefit of concurrent blockade of the renin angiotensin aldosterone system and the inhibition of neprilysin while minimizing angioedema risk. When compared to ACE inhibitor therapy in systolic heart failure patients, sacubitril/valsartan demonstrated reductions in all-cause mortality and hospitalization due to heart failure while maintaining a similar safety profile. WHAT IS NEW AND CONCLUSION: A formulation that contains both sacubitril and valsartan was manufactured and approved by the FDA in July 2015 for the reduction of mortality and hospitalization in systolic heart failure patients. The new medication offers a potentially superior alternative to ACE inhibitor therapy in the management of systolic heart failure. The effects of treatment with sacubitril/valsartan in the setting of diastolic heart failure are currently under investigation in clinical trials. PMID- 26992460 TI - The antibiotic of choice determined by antibiogram in maxillary sinus elevation surgery: a clinical study. AB - OBJECTIVES: This study set out to make antibiograms of positive bacteria cultures in samples collected when performing maxillary sinus elevations to determine a specific and effective antibiotic in each case. MATERIAL AND METHODS: A total of 174 patients (90 women and 84 men) with a mean age of 55.92 years underwent 227 sinus elevations. As the membrane was lifted, a sample was collected from the maxillary sinus floor with a cotton swab and placed on a blood agar and chocolate agar culture to incubate for 48 h at 37 degrees ; the samples then underwent microbiological analysis. Antibiograms were made for each positive culture to identify the most sensitive antibiotic, which were regrouped according to their mechanism of action as: beta-lactam (penicillins), beta-lactam (cephalosporins), macrolides, quinolones, fosfomycin, aminoglycosides, or trimethoprim sulfamethoxazole. RESULTS: Of 227 cultures, 18.1% were bacteria-positive. Of the germs, 45% were of the Streptococcus genus, most of which belonged to the Streptococcus viridans group (61.1%). The germs studied showed greater resistance to macrolides and greater sensitivity to penicillins, cephalosporins, and ciprofloxacin. The antibiotics that showed the greatest efficacy were as follows: ampicillin, amoxicillin-clavulanate, and ciprofloxacin. CONCLUSIONS: On the basis of antibiograms of positive cultures, the antibiotics presenting the greatest efficacy against possible complications were as follows: ampicillin, amoxicillin clavulanate, and ciprofloxacin. Clinically, the antibiograms proved useful as they allowed the prescription of specific antibiotics to resolve possible postoperative sinus infections. PMID- 26992461 TI - Case of basal cell carcinoma with myoepithelial differentiation: Its characteristic clinical and histopathological features. PMID- 26992463 TI - Methylmalonic acid and neutrophil morphometric index in laboratory diagnosis of cobalamin deficiency without macrocytosis. AB - INTRODUCTION: This study aimed to investigate the utility of methylmalonic acid (MMA) and neutrophil Cell Population Data, available on the Beckman Coulter LH750 Analyser (Miami, FL, USA), in laboratory assessment of cobalamin status in patients at risk of cobalamin deficiency, without macrocytosis and inflammation. METHODS: The study group included 189 patients. Neutrophil Cell Population Data along with vitamin B12 and homocysteine were assessed in regard to MMA tertile groups. RESULTS: Statistically significant differences were between lower and upper MMA tertile in serum B12 (P ? 0.001), homocysteine (P = 0.001) and neutrophil morphometric index, NeS-DW (P = 0.029). Also, serum B12 concentrations were significantly different between lower and middle MMA tertile, P = 0.005. Receiver operating characteristic analysis of NeS-DW ability to detect MMA?367 nmol/L revealed a significant area under the curve AUC = 0.761 P ? 0.001 95% CI 0.693-0.830. Optimal cut-off value was NeS-DW?3.51% with sensitivity of 74.19% and specificity of 68.87%. CONCLUSION: In patients at risk of cobalamin deficiency and normal MCV, classification according to MMA revealed cobalamin status differences. Neutrophil morphometric index may be an indicator of early changes in neutrophil nucleus morphology caused by impaired cobalamin status. PMID- 26992462 TI - Improving Therapeutic Potential of Farnesylthiosalicylic Acid: Tumor Specific Delivery via Conjugation with Heptamethine Cyanine Dye. AB - The RAS and mTOR inhibitor S-trans-trans-farnesylthiosalicylic acid (FTS) is a promising anticancer agent with moderate potency, currently undergoing clinical trials as a chemotherapeutic agent. FTS has displayed its potential against a variety of cancers including endocrine resistant breast cancer. However, the poor pharmacokinetics profile attributed to its high hydrophobicity is a major hindrance for its continued advancement in clinic. One of the ways to improve its therapeutic potential would be to enhance its bioavailability to cancer tissue by developing a method for targeted delivery. In the current study, FTS was conjugated with the cancer-targeting heptamethine cyanine dye 5 to form the FTS dye conjugate 11. The efficiency of tumor targeting properties of conjugate 11 against cancer cell growth and mTOR inhibition was evaluated in vitro in comparison with parent FTS. Cancer targeting of 11 in a live mouse model of MCF7 xenografts was demonstrated with noninvasive, near-infrared fluorescence (NIRF) imaging. The results from our studies clearly suggest that the bioavailability of FTS is indeed improved as indicated by log P values and cancer cell uptake. The FTS-dye conjugate 11 displayed higher potency (IC50 = 16.8 +/- 0.5 MUM) than parent FTS (IC50 = ~51.3 +/- 1.8 MUM) and inhibited mTOR activity in the cancer cells at a lower concentration (12.5 MUM). The conjugate 11 was shown to be specifically accumulated in tumors as observed by in vivo NIRF imaging, organ distribution, and ex vivo tumor histology along with cellular level confocal microscopy. In conclusion, the conjugation of FTS with cancer-targeting heptamethine cyanine dye improved its pharmacological profile. PMID- 26992464 TI - Prevalence of apical periodontitis and root filled teeth in a Belgian subpopulation found on CBCT images. AB - AIM: To investigate the prevalence of apical periodontitis (AP) and root filled teeth found on cone-beam computed tomography (CBCT) scans in a Belgian subpopulation in a retrospective cross-sectional study. METHODOLOGY: At the university hospital of Leuven, 804 patients received a CBCT scan between 01/01/2013 and 01/01/2014. The investigated sample included 631 scans with a permanent dentition and a total of 11 117 teeth. Prevalences and their confidence intervals are reported and the association between treatment, position of a tooth, gender and age with AP was determined using logistic regressions. RESULTS: A total of 656 teeth (5.9%) had signs of AP and 1357 teeth (12.2%) had been root filled. AP was present in 212 of the 9760 nonroot filled teeth (2.2%) and in 444 of the 1357 root filled teeth (32.7%). Adequate root fillings were detected in approximately half (49.3%) of the root filled teeth. The prevalence of AP was 22.8% when the root filling was adequate, when scored inadequate the prevalence increased to 41%. Univariate and multivariable logistic regression analyses revealed a significant relation of tooth position and treatment with AP. No difference in the prevalence of AP between male and female patients was detected. CONCLUSION: The prevalence of AP was comparable with findings in other epidemiological studies. Root filled teeth had significantly more AP than nonroot filled teeth. The technical quality of the root fillings had a significant impact on the presence of AP. Therefore, emphasis on the quality of work and continuing education in the field of Endodontology must be provided in Belgium. PMID- 26992465 TI - Patient monitoring with Google Glass: a pilot study of a novel monitoring technology. AB - BACKGROUND: Head-mounted devices (HMDs) are of significant interest for applications within medicine, including in anesthesia for patient monitoring. Previous devices trialed in anesthesia for this purpose were often bulky, involved cable tethers, or were otherwise ergonomically infeasible. Google Glass is a modern HMD that is lightweight and solves many of the issues identified with previous HMDs. AIM: To examine the acceptance of Google Glass as a patient monitoring device in a pediatric anesthesia context at Princess Margaret Hospital for Children, Perth, Australia. METHODS: We developed a custom-designed software solution for integrating Google Glass into the anesthesia environment, which enabled the device user to continuously view patient monitoring parameters transmitted wirelessly from the anesthesia workstation. RESULTS: A total of 40 anesthetists were included in the study. Each anesthetist used the device for the duration of a theater list. We found 90% of anesthetists trialing the device agreed that it was comfortable to wear, 86% agreed the device was easy to read, and 82.5% agreed the device was not distracting. In 75% of cases, anesthetists reported unprompted that they were comfortable using the device in theater. Anesthetists reported that they would use the device again in 76% of cases, and indicated that they would recommend the device to a colleague in 58% of cases. CONCLUSION: Given the pilot nature of this study, we consider these results highly favorable. Anesthetists readily accepted Google Glass in the anesthetic environment, with further enhancements to device software, rather than hardware, now being the barrier to adoption. There are a number of applications for HMDs in pediatric anesthesia. PMID- 26992469 TI - Pathogen-induced conditioning of the primary xylem vessels - a prerequisite for the formation of bacterial emboli by Pectobacterium atrosepticum. AB - Representatives of Pectobacterium genus are some of the most harmful phytopathogens in the world. In the present study, we have elucidated novel aspects of plant-Pectobacterium atrosepticum interactions. This bacterium was recently demonstrated to form specific 'multicellular' structures - bacterial emboli in the xylem vessels of infected plants. In our work, we showed that the process of formation of these structures includes the pathogen-induced reactions of the plant. The colonisation of the plant by P. atrosepticum is coupled with the release of a pectic polysaccharide, rhamnogalacturonan I, into the vessel lumen from the plant cell wall. This polysaccharide gives rise to a gel that serves as a matrix for bacterial emboli. P. atrosepticum-caused infection involves an increase of reactive oxygen species (ROS) levels in the vessels, creating the conditions for the scission of polysaccharides and modification of plant cell wall composition. Both the release of rhamnogalacturonan I and the increase in ROS precede colonisation of the vessels by bacteria and occur only in the primary xylem vessels, the same as the subsequent formation of bacterial emboli. Since the appearance of rhamnogalacturonan I and increase in ROS levels do not hamper the bacterial cells and form a basis for the assembly of bacterial emboli, these reactions may be regarded as part of the susceptible response of the plant. Bacterial emboli thus represent the products of host-pathogen integration, since the formation of these structures requires the action of both partners. PMID- 26992470 TI - Caught in the act: the crystal structure of cleaved cathepsin L bound to the active site of Cathepsin L. AB - Cathepsin L is a ubiquitously expressed papain-like cysteine protease involved in the endosomal degradation of proteins and has numerous roles in physiological and pathological processes, such as arthritis, osteoporosis, and cancer. Insight into the specificity of cathepsin L is important for elucidating its physiological roles and drug discovery. To study interactions with synthetic ligands, we prepared a presumably inactive mutant and crystallized it. Unexpectedly, the crystal structure determined at 1.4 A revealed that the cathepsin L molecule is cleaved, with the cleaved region trapped in the active site cleft of the neighboring molecule. Hence, the catalytic mutant demonstrated low levels of catalytic activity. PMID- 26992471 TI - Effects of number of training generations on genomic prediction for various traits in a layer chicken population. AB - BACKGROUND: Genomic estimated breeding values (GEBV) based on single nucleotide polymorphism (SNP) genotypes are widely used in animal improvement programs. It is typically assumed that the larger the number of animals is in the training set, the higher is the prediction accuracy of GEBV. The aim of this study was to quantify genomic prediction accuracy depending on the number of ancestral generations included in the training set, and to determine the optimal number of training generations for different traits in an elite layer breeding line. METHODS: Phenotypic records for 16 traits on 17,793 birds were used. All parents and some selection candidates from nine non-overlapping generations were genotyped for 23,098 segregating SNPs. An animal model with pedigree relationships (PBLUP) and the BayesB genomic prediction model were applied to predict EBV or GEBV at each validation generation (progeny of the most recent training generation) based on varying numbers of immediately preceding ancestral generations. Prediction accuracy of EBV or GEBV was assessed as the correlation between EBV and phenotypes adjusted for fixed effects, divided by the square root of trait heritability. The optimal number of training generations that resulted in the greatest prediction accuracy of GEBV was determined for each trait. The relationship between optimal number of training generations and heritability was investigated. RESULTS: On average, accuracies were higher with the BayesB model than with PBLUP. Prediction accuracies of GEBV increased as the number of closely related ancestral generations included in the training set increased, but reached an asymptote or slightly decreased when distant ancestral generations were used in the training set. The optimal number of training generations was 4 or more for high heritability traits but less than that for low heritability traits. For less heritable traits, limiting the training datasets to individuals closely related to the validation population resulted in the best predictions. CONCLUSIONS: The effect of adding distant ancestral generations in the training set on prediction accuracy differed between traits and the optimal number of necessary training generations is associated with the heritability of traits. PMID- 26992472 TI - Solid organ transplant patients: are there opportunities for antimicrobial stewardship? AB - OBJECTIVE: Rising incidence of Clostridium difficile and multidrug-resistant organisms' infections and a dwindling development of new antimicrobials are an impetus for antimicrobial stewardship in organ transplant recipients. We sought to understand antimicrobial prescribing practices and identify opportunities for interdisciplinary collaboration among the transplant, antimicrobial stewardship, and infectious diseases teams. METHODS: In 2013, two assessors conducted four real-time audits on all antimicrobial therapy in transplant patients, assessing each regimen against stewardship principles established by the Centers for Disease Prevention and Control, supplemented by applicable transplant-specific infection guidelines. Chi-square test was used to compare stewardship-concordant and stewardship-discordant audit results relative to transplant infectious diseases consultation. RESULTS: Analysis was performed on 176 audits. Fifty-eight percent (103/176) received at least one antimicrobial, of which 69.9% (72/103) were stewardship-concordant. Infections were confirmed or suspected in 52.3% (92/176). Of those, 98.9% (91/92) received antimicrobials, and 41.8% (38/91) were prescribed by transplant clinicians. Infectious diseases consultation was associated with more stewardship-concordant prescriptions (78.5% vs. 59.6%, p = 0.03). The most common stewardship-discordant categories were lack of de escalation, empiric antimicrobial spectrum being too broad, and therapy duration being too long. CONCLUSIONS: Opportunities exist for antimicrobial stewardship in transplant recipients, especially those who do not require infectious diseases consultation. PMID- 26992473 TI - A case of Canavan disease with microcephaly. AB - BACKGROUND: Canavan disease is an autosomal recessive disorder with spongy degeneration of white matter of the brain. It presents with developmental delay, visual problems and macrocephaly. PATIENT DESCRIPTION: We report a ten-month old boy with Canavan disease who presented with global developmental delay, seizures, abnormal eye movements and microcephaly. RESULTS: MRI brain revealed diffuse involvement of the supra tentorial white matter, globus pallidi, thalami, dentate nuclei and brainstem with sparing of the corpus callosum. The genetic testing revealed homozygous mutation of aspartoacylase gene [c.859 G>A (p.Ala287Thr)] in Exon 6. CONCLUSION: Possibility of Canavan disease should be considered even in the presence of microcephaly. PMID- 26992475 TI - Diffusion restriction in ethylmalonic encephalopathy - An imaging evidence of the pathophysiology of the disease. AB - Ethylmalonic encephalopathy is an inborn error of metabolism characterized by encephalopathy, petechiae chronic diarrhea and acrocyanosis. Imaging findings include patchy signal changes in the basal ganglia, periaqueductal region, subcortical white matter and cerebellum. We describe the novel finding of diffusion restriction in brain lesions, in a proven case of ethylmalonic encephalopathy. PMID- 26992474 TI - Self-concept in children and adolescents with epilepsy: The role of family functioning, mothers' emotional symptoms and ADHD. AB - PURPOSE: This study aimed to identify the associated factors of poor self-concept in children and adolescents with epilepsy. METHODS: Fifty-three patients with uncomplicated epilepsy (aged 7-18years) and 28 healthy controls were included. Study measures included the Piers-Harris 2 Self-Concept Scale, Family Assessment Device (FAD), Turgay DSM-IV based ADHD rating Scale (T-DSM-IV-S), Conners' Teacher Rating Scale (CTRS-R), Beck Depression Inventory and State-Trait Anxiety Inventory (STAI). Neurology clinic charts were reviewed for the epilepsy-related variables. RESULTS: While the Piers-Harris 2 total score was not significantly different between the groups, patients with epilepsy had lower (poorer) scores on freedom from anxiety and popularity subscales. Linear regression analysis revealed that the problem solving, affective responsiveness, general functioning and communication scores of FAD; total and inattentiveness scores of T-DSM-IV-S and mothers' Beck scores were associated with the total score of Piers-Harris 2. Epilepsy-related factors were not found to be associated with self-concept scores. CONCLUSION: Poor self-concept in children with epilepsy is associated with negative family functioning, mothers' emotional symptoms and ADHD, especially the symptoms of inattentiveness. PMID- 26992477 TI - Computer-assisted template-guided custom-designed 3D-printed implant placement with custom-designed 3D-printed surgical tooling: an in-vitro proof of a novel concept. AB - OBJECTIVES: The aim of this study was to introduce a new concept for computer assisted template-guided placement of a custom 3D-designed/3D-printed implant with congruent custom 3D-designed/3D-printed surgical tooling and to test the feasibility and accuracy of this method in-vitro. MATERIALS AND METHODS: One partially edentulous human mandibular cadaver was scanned with a cone-beam computed tomography (CBCT) system and intra-oral scan system. The 3D data of this cadaver were imported in specialized software and used to analyse the region of a missing tooth. Based on the functional and anatomical parameters, an individual implant with congruent surgical tooling and surgical guided template was designed and 3D-printed. The guided osteotomy was performed, and the custom implant inserted. To evaluate the planned implant position in comparison with the placed implant position, the mandible with implant was scanned again with the CBCT system and software matching was applied to measure the accuracy of the procedure. RESULTS: The angular deflection with the planned implant position was 0.40 degrees . When comparing the 3D positions of the shoulder, there is a deviation of 0.72 mm resulting in an apical deviation of 0.72 mm. CONCLUSION: With the use of currently available technology, it is very well feasible to create in a virtual simulation a custom implant with congruent custom surgical tooling and to transfer this to a clinical setting. However, further research on multiple levels is needed to explore this novel approach. PMID- 26992476 TI - Protective effects of quercetin against arsenic-induced testicular damage in rats. AB - This study investigated the effect of quercetin on changes in testes due to arsenic exposure. Twenty-seven male rats were divided into three groups: control (10 ml kg-1 day-1 saline), arsenic (10 mg kg-1 day-1 sodium arsenite) and arsenic + quercetin (arsenic + 50 mg kg-1 day-1 quercetin). The rats were sacrificed at the end of 15-day experiment. There was no difference between control group and arsenic group in body weight gain, testicular weight and serum total testosterone level. Quercetin treatment did not cause a significant difference in these parameters. In the arsenic group rats, we determined deterioration in the structure of seminiferous tubules, a decrease in the number of spermatogenic cells, an increase in the number of apoptotic cells, a decrease in the number of PCNA-positive cells, a decrease in SOD, CAT and GSH-Px activities, and an increase in the MDA level in testicular tissue. In all these changes, arsenic+quercetin group showed an improved compared to arsenic group. The amount of arsenic increased in the arsenic group was compared to the control group, and there was no difference between arsenic group and arsenic + quercetin group in the amount of arsenic. In conclusion, quercetin prevented arsenic induced testicular damage with its anti-apoptotic and antioxidant effects. PMID- 26992478 TI - Clinical study of Dermatophyte Test Strip, an immunochromatographic method, to detect tinea unguium dermatophytes. AB - The Dermatophyte Test Strip visualizes mycotic antigens by immunochromatography. It allows easy and fast detection of dermatophytes. A multicenter, single-arm, comparative clinical study was designed to evaluate the capacity of Dermatophyte Test Strip to detect dermatophytes in suspected tinea unguium specimens in comparison with direct microscopy and polymerase chain reaction (PCR). Signed consent was obtained from 222 subjects and all subjects completed the study. With the Dermatophyte Test Strip, dermatophytes were detected in 201 of 222 (90.5%) specimens but not in 21 of 222 (9.5%) specimens. With direct microscopy, dermatophytes were detected in 170 of 222 (76.6%) specimens but not in 52 of 222 (23.4%). Of the 45 specimens that showed inconsistent results between the two methods, PCR gave further results for 40 specimens, of which 37 (92.5%) specimens were positive and three (7.5%) were negative for dermatophytes. The positive concordance rate, negative concordance rate and overall concordance rate between the Dermatophyte Test Strip and direct microscopy were 81.1%, 66.7% and 79.7%, respectively. When inconsistent results were corrected using the results of PCR, these rates were 97.5%, 71.4% and 95.0%, respectively. When five specimens that could not be tested by PCR because no piece for the PCR test was left were excluded from analysis, these rates were 99.0%, 78.9% and 97.2%, respectively. The present results indicate good detection capacity of the Dermatophyte Test Strip. The Dermatophyte Test Strip provides a reliable, convenient and quick method to test for tinea unguium. PMID- 26992479 TI - Sodium Thiosulfate and the Anion Gap in Patients Treated by Hemodialysis. PMID- 26992480 TI - BK Polyomavirus Tubulointerstitial Nephritis With Urothelial Hyperplasia in a Kidney Transplant. AB - Polyomavirus nephropathy is characterized histopathologically by evidence of viral replication and acute tubular injury with interstitial inflammation, tubulitis, and intranuclear inclusions. Polyomavirus nephropathy typically develops in the kidney transplant as a combination of the unique nature of the transplanted tissue and the immunomodulated status of the patient. We present a case in which a patient had lingering BK viremia and declining kidney function following receipt of lung and kidney transplants. A kidney biopsy was performed, which demonstrated BK polyomavirus tubulointerstitial nephritis, resultant cytopathic changes and tubular/ductal injury, associated urothelial hyperplasia with foci of squamous metaplasia, suspected membranous glomerulopathy, and moderate arterial/arteriolar sclerosis. There was also evidence of more proximal nephron viral involvement, with glomerular parietal epithelium infection and injury present. This case shows impressive BK polyomavirus-associated urothelial hyperplasia in the kidney, which to our knowledge has not been previously illustrated in the literature. There have been numerous studies attempting to show the association of polyomaviruses with the development of carcinoma, and this case report is significant because it is an example of viral-induced changes that are concerning and hold potential for malignant transformation. PMID- 26992481 TI - Interface pressure redistribution on skin during continuous lateral rotation therapy: A feasibility study. AB - BACKGROUND: Continuous Lateral Rotation Therapy (CLRT) is a therapy used in ICUs for early mobilization of ventilated patients. CLRT is believed by some in health care to not be sufficient to allow for capillary re-perfusion, and may lead to tissue damage. OBJECTIVES: To determine if there are differences in skin interface pressures, skin integrity, or perceived discomfort across three positioning scenarios. METHODS: A Hill-Rom Total Care SpOrt((r)) bed was equipped with a pressure mapping device. Ten healthy volunteers were placed in each positioning scenario for 30 minutes; interface pressures were recorded. RESULTS: CLRT alone demonstrated statistically lower interface pressures on ischial tuberosities (p < 0.05) as compared to the scenarios with static wedge. Higher pressures were noted on the heels in CLRT alone (p < 0.05). One subject noted pain with CLRT. No erythema or breakdown noted. CONCLUSIONS: This feasibility study supports the use of CLRT to decrease pressure on capillary beds and decrease patient discomfort. PMID- 26992482 TI - Persuasive user experiences of a health Behavior Change Support System: A 12 month study for prevention of metabolic syndrome. AB - BACKGROUND: Obesity has become a severe health problem in the world. Even a moderate 5% weight loss can significantly reduce the prevalence of metabolic syndrome, which can be vital for preventing comorbidities caused by the obesity. Health Behavior Change Support Systems (hBCSS) emphasize an autogenous approach, where an individual uses the system to influence one's own attitude or behavior to achieve his or her own goal. Regardless of promising results, such health interventions technology has often been considered merely as a tool for delivering content that has no effect or value of its own. More research on actual system features is required. OBJECTIVES: The objective of this study is to describe how users perceive persuasive software features designed and implemented into a support system. METHODS: The research medium in this study is a web-based information system designed as a lifestyle intervention for participants who are at risk of developing a metabolic syndrome or who are already suffering from it. The system was designed closely following the principles of the Persuasive Systems Design (PSD) model and the Behavior Change Support Systems (BCSS) framework. A total of 43 system users were interviewed for this study during and after a 52 week intervention period. In addition, the system's login data and subjects' Body Mass Index (BMI) measures were used to interpret the results. RESULTS: This study explains in detail how the users perceived using the system and its persuasive features. Self-monitoring, reminders, and tunneling were perceived as especially beneficial persuasive features. The need for social support appeared to grow along the duration of the intervention. Unobtrusiveness was found to be very important in all stages of the intervention rather than only at the beginning. CONCLUSIONS: Persuasive software features have power to affect individuals' health behaviors. Through their systematicity the PSD model and the BCSS framework provide effective support for the design and development of technological health interventions. Designers of such systems may choose, for instance, to implement more self-monitoring tools to help individuals to adjust their personal goals with the system's offerings better. PMID- 26992483 TI - Influence of Screen-Based Peer Modeling on Preschool Children's Vegetable Consumption and Preferences. AB - OBJECTIVE: To determine the influence of screen-based peer modeling on children's vegetable consumption and preference. METHODS: A total of 42 children aged 3-5 years were randomly assigned to view individually a video segment of peers consuming a modeled vegetable (bell pepper), vs a nonfood video segment or no video. Analysis of covariance models examined bell pepper preference and consumption during initial video exposure (day 1) and without video exposure (days 2 and 7), adjusted for age, sex, body mass index, and initial bell pepper consumption. RESULTS: Children in the vegetable condition ate more bell peppers (15.5 g) than did those in the control condition (5.9 g; P = .04; model eta(2) = 0.85) on day 7, with no differences on days 1 or 2. Among children who ate the modeled vegetable, those in the vegetable DVD condition reported greater preference for eating the vegetable again (P = .01). CONCLUSIONS AND IMPLICATIONS: Screen-based peer modeling is a promising tool to influence children's vegetable consumption. PMID- 26992484 TI - Smoking, vaping, eating: Is legalization impacting the way people use cannabis? AB - BACKGROUND: In the context of the shifting legal landscape of medical cannabis, different methods of cannabis administration have important public health implications. How medical marijuana laws (MML) may influence patterns of use of alternative methods of cannabis administration (vaping and edibles) compared to traditional methods (smoking) is unclear. The purpose of this study was to determine if the prevalence of use of alternative methods of cannabis administration varied in relation to the presence of and variation in MMLs among states in the United States. METHOD: Using Qualtrics and Facebook, we collected survey data from a convenience sample of n=2838 individuals who had used cannabis at least once in their lifetime. Using multiple sources, U.S. states were coded by MML status, duration of MML status, and cannabis dispensary density. Adjusted logistic and linear regression analyses were used to analyze outcomes of ever use, preference for, and age of initiation of smoking, vaping, and edibles in relation to MML status, duration of MML status, and cannabis dispensary density. RESULTS: Individuals in MML states had a significantly higher likelihood of ever use of vaping (OR: 2.04, 99% CI: 1.62-2.58) and edibles (OR: 1.78, 99% CI: 1.39 2.26) than those in states without MMLs. Longer duration of MML status and higher dispensary density were also significantly associated with ever use of vaping and edibles. CONCLUSIONS: MMLs are related to state-level patterns of utilization of alternative methods of cannabis administration. Whether discrepancies in MML legislation are causally related to these findings will require further study. If MMLs do impact methods of use, regulatory bodies considering medical or recreational legalization should be aware of the potential impact this may have on cannabis users. PMID- 26992485 TI - Cannabis and adolescents: Exploring the substance misuse treatment provider experience in a climate of legalization. AB - BACKGROUND: Understanding consumer attitudes toward drugs is vital for the design and implementation of effective substance misuse prevention and treatment programs. Research that enhances our understanding of these perceptions is of the utmost importance in the climate of cannabis legalization. While there is a body of literature focused on the perceptions of drug use among adolescents, less attention has been paid to the experiences of health care professionals who serve this vulnerable population. Research aimed at better understanding the experiences of professionals may improve cannabis misuse prevention efforts and inform policy decisions as cannabis moves closer to legalization nationwide. METHODS: The present study applied a grounded theory qualitative methodology to interview 11 adolescent substance misuse treatment providers. Each participant had at least two years of clinical practice in Colorado before January 1, 2014, when cannabis became available for recreational sale. FINDINGS: Extensive analysis of data obtained from participant interviews, yielded seven core concepts related to cannabis use and decriminalization: normalizing, increasing access, rising addiction potential, link to opioids and other drugs, complicating substance treatment, diversity issues, and responding to change. According to participants, legalization has contributed to the continuing normalization of cannabis, validation of its consumption, and greater access to a host of new and more potent THC products by adolescents. Providers attributed these attitudinal changes to heavier use of both cannabis and other drugs and increased resistance to treatment efforts and interventions. CONCLUSIONS: These results support the need to expand access to a wider range of substance misuse treatment options for adolescents and to further our understanding of the impact on this population of the cannabis laws. PMID- 26992486 TI - Diagnostic Difficulties With Atrophy, Atypical Adenomatous Hyperplasia, and Atypical Small Acinar Proliferation: A Systematic Review of Current Literature. AB - Prostate cancer is the second leading cause of cancer death in men, behind only lung cancer. In some cases, the proper diagnosis of prostatic neoplasia can be challenging, and the differential diagnosis includes atypical nonmalignant lesions such as atrophy, atypical adenomatous hyperplasia (AAH), and atypical small acinar proliferation (ASAP). Atrophy and AAH have a benign clinical outcome, and if detected on needle biopsy or transurethral resection of the prostate, clinical follow-up seems appropriate. In contrast, ASAP cannot be determined to be benign or malignant. In clinical practice, the diagnosis of ASAP is an indication for repeat biopsy because the chance of finding prostate adenocarcinoma is even greater than that with an earlier diagnosis of high-grade prostatic intraepithelial neoplasia. Malignant lesions require more restrictive treatment; therefore, differentiation among atrophy, AAH, ASAP, and adenocarcinoma is essential. We performed a systematic review of the current data allow to the creation of a diagnostic algorithm for atrophy, AAH, ASAP, and adenocarcinoma. We propose an algorithm that covers the practical issues related to interpretation of the biopsy findings and how to proceed further. PMID- 26992487 TI - Lumbosacral Plexus Involvement as the First Site of Metastatic Recurrence in a Patient With CTNNB1-Mutant Prostate Cancer. PMID- 26992488 TI - Preparation of hybrid molecularly imprinted polymer with double-templates for rapid simultaneous purification of theophylline and chlorogenic acid in green tea. AB - A novel double-templates technique was adopted for solid-phase extraction packing agent, and the obtained hybrid molecularly imprinted polymers with double templates (theophylline and chlorogenic acid) were characterized by fourier transform infrared and field emission scanning electron microscope. The molecular recognition ability and binding capability for theophylline and chlorogenic acid of polymers was evaluated by static absorption and dynamic adsorption curves. A rapid and accurate approach was established for simultaneous purification of theophylline and chlorogenic acid in green tea by coupling hybrid molecularly imprinted solid-phase extraction with high performance liquid chromatography. With optimization of SPE procedure, a reliable analytical method was developed for highly recognition towards theophylline and chlorogenic acid in green tea with satisfactory extraction recoveries (theophylline: 96.7% and chlorogenic acid: 95.8%). The limit of detection and limit of quantity of the method were 0.01 MUg/mL and 0.03 MUg/mL for theophylline, 0.05 MUg/mL and 0.17 MUg/mL for chlorogenic acid, respectively. The recoveries of proposed method at three spiked levels analysis were 98.7-100.8% and 98.3-100.2%, respectively, with the relative standard deviation less than 1.9%. Hybrid molecularly imprinted polymers with double-templates showed good performance for two kinds of targets, and the proposed approach with high affinity of hybrid molecularly imprinted polymers might offer a novel method for the purification of complex samples. PMID- 26992489 TI - Structure prediction of methyoxy-polybrominated diphenyl ethers (MeO-PBDEs) through GC-MS analysis of their corresponding PBDEs. AB - It is hard to quantify the trace pollutants in the environment without the corresponding reference standards. Structure identifications of unknown organic pollutants are thus of great importance in environmental analysis. As for polybrominated diphenyl ethers (PBDE) with one substituent of methoxyl group, there are 837 congeners, but only 32 standards are commercially available. In this work, an effective method based on gas chromatography coupled with mass spectrometry (GC-MS) was proposed to predict the potential structures of methoxylated polybrominated diphenyl ethers (MeO-PBDEs). The mass fragmentation pattern using SIM mode not only provided the useful information on the substitution position of methoxyl group, the number of Br atoms, but also guaranteed the high sensitivity for trace analysis. Br distribution patterns of the unknown MeO-PBDEs were revealed by a linear regression model with dummy variables which described the retention time relationship between MeO-PBDEs and the corresponding PBDEs on different types of GC columns. This method was successfully used to identify three new MeO-PBDEs metabolites of BDE-28 as 4-MeO BDE-22, 4'-MeO-BDE-25 and 4-MeO-BDE-31 in the pumpkins. Therefore, the newly developed structure prediction model based on GC-MS behavior is helpful in the evaluation of unknown PBDE metabolites in the environment. PMID- 26992490 TI - Isocratic LC-DAD-FLD method for the determination of flavonoids in paprika samples by using a rapid resolution column and post-column pH change. AB - The determination of flavonoid compounds in paprika samples has been performed by liquid chromatography in series diode array and fluorescence detection (LC-DAD FLD), by means of a pH change to basic medium just before FLD detection. The validation of the method was performed through the establishment of the external standard calibration curves and the analytical figures of merit. Limits of detection ranging from 0.006 to 0.02 mg L(-1) and 0.007 to 0.09 mg L(-1) were achieved using DAD and FLD detection, respectively. The experimental conditions to carry out the hydrolysis procedure to obtain flavonoid aglycones from flavonoid glycosides have been optimized applying an experimental design and the response surface methodology. The final conditions selected were 2.5M HCl during 45 min at 85 degrees C. The repeatability of this procedure was assayed and relative standard deviation (RSD) values for concentration of quercetin and luteolin compounds were lower than 2%. The quantification of quercetin, luteolin and kaempferol compounds was carried out in less than 6 min in paprika samples by means of the external standard calibration. The analytes were extracted with methanol and the extracts were previously subjected to a cleanup procedure to extend the use of the chromatographic column. PMID- 26992491 TI - Development of green betaine-based deep eutectic solvent aqueous two-phase system for the extraction of protein. AB - Six kinds of new type of green betaine-based deep eutectic solvents (DESs) have been synthesized. Deep eutectic solvent aqueous two-phase systems (DES-ATPS) were established and successfully applied in the extraction of protein. Betaine-urea (Be-U) was selected as the suitable extractant. Single factor experiments were carried out to determine the optimum conditions of the extraction process, such as the salt concentration, the mass of DES, the separation time, the amount of protein, the temperature and the pH value. The extraction efficiency could achieve to 99.82% under the optimum conditions. Mixed sample and practical sample analysis were discussed. The back extraction experiment was implemented and the back extraction efficiency could reach to 32.66%. The precision experiment, repeatability experiment and stability experiment were investigated. UV-vis, FT IR and circular dichroism (CD) spectra confirmed that the conformation of protein was not changed during the process of extraction. The mechanisms of extraction were researched by dynamic light scattering (DLS), the measurement of the conductivity and transmission electron microscopy (TEM). DES-protein aggregates and embraces phenomenon play considerable roles in the separation process. All of these results indicated that betaine-based DES-ATPS may provide a potential substitute new method for the separation of proteins. PMID- 26992492 TI - Direct determination of sorbitol and sodium glutamate by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) in the thermostabilizer employed in the production of yellow-fever vaccine. AB - Reference methods for quality control of vaccines usually require treatment of the samples before analysis. These procedures are expensive, time-consuming, unhealthy and require careful manipulation of the sample, making them a potential source of analytical errors. This work proposes a novel method for the quality control of thermostabilizer samples of the yellow fever vaccine employing attenuated total reflectance Fourier transform infrared spectrometry (ATR-FTIR). The main advantage of the proposed method is the possibility of direct determination of the analytes (sodium glutamate and sorbitol) without any pretreatment of the samples. Operational parameters of the FTIR technique, such as the number of accumulated scans and nominal resolution, were evaluated. The best conditions for sodium glutamate were achieved when 64 scans were accumulated using a nominal resolution of 4 cm(-1). The measurements for sodium glutamate were performed at 1347 cm(-1) (baseline correction between 1322 and 1369 cm(-1)). In the case of sorbitol, the measurements were done at 890cm(-1) (baseline correction between 825 and 910 cm(-1)) using a nominal resolution of 2 cm(-1) with 32 accumulated scans. In both cases, the quantitative variable was the band height. Recovery tests were performed in order to evaluate the accuracy of the method and recovery percentages in the range 93-106% were obtained. Also, the methods were compared with reference methods and no statistical differences were observed. The limits of detection and quantification for sodium glutamate were 0.20 and 0.62% (m/v), respectively, whereas for sorbitol they were 1 and 3.3% (m/v), respectively. PMID- 26992493 TI - A new multifunctional Schiff-based chemosensor for mask-free fluorimetric and colorimetric sensing of F- and CN-. AB - A Schiff-based chemosensor DSS was designed for selective and simultaneous detection and/or determination of F(-) and CN(-) by distinguishable changes in both solution color and spectroscopic responses within same sample due to the strong emission enhancement at distinct emission bands without any mask. In addition, the sensing mechanism was evaluated by NMR titration and DFT calculations. PMID- 26992494 TI - Rapid and direct volatile compound profiling of black and green teas (Camellia sinensis) from different countries with PTR-ToF-MS. AB - Volatile profiles of 63 black and 38 green teas from different countries were analysed with Proton Transfer Reaction-Time of Flight-Mass Spectrometry (PTR-ToF MS) both for tea leaves and tea infusion. The headspace volatile fingerprints were collected and the tea classes and geographical origins were tracked with pattern recognition techniques. The high mass resolution achieved by ToF mass analyser provided determination of sum formula and tentative identifications of the mass peaks. The results provided successful separation of the black and green teas based on their headspace volatile emissions both from the dry tea leaves and their infusions. The volatile fingerprints were then used to build different classification models for discrimination of black and green teas according to their geographical origins. Two different cross validation methods were applied and their effectiveness for origin discrimination was discussed. The classification models showed a separation of black and green teas according to geographical origins the errors being mostly between neighbouring countries. PMID- 26992495 TI - New method to determine free sterols/oxysterols in food matrices using gas chromatography and ion trap mass spectrometry (GC-IT-MS). AB - Sterols/oxysterols in food may be free or bound i.e. esterified with fatty acids. Methods commonly applied to determine those compounds in such matrices (based on various analytical techniques) usually start with hydrolysis of the food lipid fraction, which means that the results are no good indication of concentration of free sterols/oxysterols only. But only free oxysterols are proatherogenic factors, bound ones are not. There are some published methods selectively sensitive to free oxysterols only, but they are capable to determine only a few compounds and feature very low recovery rates. The aim of this work was to develop a method to determine various free (non-esterified) sterols/oxysterols in various food matrices. The developed method is based on the GC-IT-MS technique used in the chemical ionization mode. It was applied to determine 16 different free sterols/oxysterols in egg powder, cheese, butter, milk and salami. Fat extracted from the given matrix is purified on a specially prepared silica-gel bed to separate the sterol fraction from the oxysterol one. Sterols are silylated using N,O-bis(trimethylsilyl)trifluoroacetamide and trimethylchlorosilane BSTFA:TMCS, then GC-IT-MS analysed. The method features high recovery rates (75 95%), high reproducibility (RSD<20%), and sensitivity within the 0.01-0.3 mg 100 g(-1) range, depending on the analysed compound. The method is ideally suited for determination of free sterols/oxysterols. Besides, should total concentration of both free and bound forms be of interest, food lipids may be transesterificated before the silica-gel bed purification step. PMID- 26992496 TI - Self-assembled and covalently linked capillary coating of diazoresin and cyclodextrin-derived dendrimer for analysis of proteins by capillary electrophoresis. AB - Self-assembled and covalently linked capillary coatings of cyclodextrin-derived (CD) dendrimer were prepared using photosensitive diazoresin (DR) as a coupling agent. Layer by layer (LBL) self-assembled DR/CD-dendrimer coatings based on ionic bonding was fabricated first on the inner surface of capillary, and subsequently converted into covalent bonding after treatment with UV light through a unique photochemistry reaction of DR. Protein adsorption on the inner surface of capillary was suppressed by the DR/CD-dendrimer coating, and thus a baseline separation of lysozyme (Lys), myoglobin (Mb), bovine serum albumin (BSA) and ribonuclease A (RNase A) was achieved using capillary electrophoresis (CE). Compared with the bare capillary, the DR/CD-dendrimer covalently linked capillary coatings showed excellent protein separation performance with good stability and repeatability. Because of the replacement of highly toxic and moisture sensitive silane coupling agent by DR in the covalent coating preparation, this method may provide an environmentally friendly and simple way to prepare the covalently coated capillaries for CE. PMID- 26992497 TI - A novel high-throughput image based rapid Folin-Ciocalteau assay for assessment of reducing capacity in foods. AB - The aim of the presented work was to develop and validate a novel high-throughput rapid Folin-Ciocalteau assay for the quantification of reducing capacity of foods based on image scanner (Image-F-C assay). The original rapid F-C assay using a 96 well plate was improved by adding a neutralization step that stabilizes the formed color, enabling image acquisition using a flatbed scanner. Although the scanner has been already used in other analytical applications, no analysis has been reported regarding the effect of the scanner model, the plate orientation or the reaction volume. In the present study, we establish that the mentioned parameters do affect the linearity and precision of image based Folin-Ciocalteau assay, and provide the optimal scanning conditions for the analyzed scanner models. Euclidean distance calculated from R (Red), G (Green) and B (Blue) values was chosen, based on linearity and sensitivity, in order to quantify the reducing capacity. An in-house program using free ImageJ macro language was written to calculate automatically the RGB values of each well. The Image-F-C assay is linear within the range of 0-20 mg L(-1) of gallic acid (R(2)>=0.9939). We compared reducing capacity values from real samples quantified by the image F-C assay and by a microplate reader and an inter-day relative standard error<8% was observed. Bland-Altman and correlation analyzes showed that there were no significant differences between the two methods. PMID- 26992498 TI - Calibration of a passive sampler based on stir bar sorptive extraction for the monitoring of hydrophobic organic pollutants in water. AB - A passive sampler based on stir bars coated with polydimethylsiloxane (PDMS) was calibrated for the measurement of time-weighted average concentrations of hydrophobic micropollutants, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls and organochlorine pesticides, in water. Stir bar/water partition coefficients were measured by equilibrating bars with sheets made of silicone rubber material for which partition coefficients had been reported previously. Kinetic parameters characterising the exchange of analytes between stir bars and water were determined under controlled exposure conditions using a passive dosing system. The dosing system consisted of silicone rubber sheets with a large surface area, spiked with analytes. During stir bar sampler exposure, analytes partitioned from dosing sheets to water in the exposure tank and maintained constant exposure concentrations. Reversible and isotropic exchange kinetics of analytes between sampler and water was confirmed by measuring the release of a range of performance reference compounds (PRCs) from stir bars. Application of a two-resistance model confirmed that, except for hexachlorocyclohexane isomers, uptake of the test compounds under the experimental conditions was controlled by diffusion in the water boundary layer. This permits the application of PRCs for in situ calibration of uptake kinetics of test compounds to stir bars. PMID- 26992499 TI - Sensitive determination of estrogens in environmental waters treated with polymeric ionic liquid-based stir cake sorptive extraction and liquid chromatographic analysis. AB - A simple, sensitive and environmentally friendly method using polymeric ionic liquid-based stir cake sorptive extraction followed by high performance liquid chromatography with diode array detection (HPLC/DAD) has been developed for efficient quantification of six selected estrogens in environmental waters. To extract trace estrogens effectively, a poly (1-ally-3-vinylimidazolium chloride co-ethylene dimethacrylate) monolithic cake was prepared and used as the sorbent of stir cake sorptive extraction (SCSE). The effects of preparation conditions of sorbent and extraction parameters of SCSE for estrogens were investigated and optimized. Under optimal conditions, the developed method showed satisfactory analytical performance for targeted analytes. Low limits of detection (S/N=3) and quantification limits (S/N=10) were achieved within the range of 0.024-0.057 ug/L and 0.08-0.19 ug/L, respectively. Good linearity of method was obtained for analytes with the correlation coefficients (R(2)) above 0.99. At the same time, satisfactory method repeatability and reproducibility was achieved in terms of intra- and inter-day precisions, respectively. Finally, the established SCSE HPLC/DAD method was successfully applied for the determination of estrogens in different environmental water samples. Recoveries obtained for the determination of estrogens in spiked samples ranged from 71.2% to 108%, with RSDs below 10% in all cases. PMID- 26992500 TI - Exploring bitterness of traditional Chinese medicine samples by potentiometric electronic tongue and by capillary electrophoresis and liquid chromatography coupled to UV detection. AB - Instrumental bitterness assessment of traditional Chinese herbal medicine (TCM) preparations was addressed in this study. Three different approaches were evaluated, high-performance liquid chromatography coupled to UV detector (HPLC), capillary electrophoresis coupled to UV detector (CE) and a potentiometric multisensor system - electronic tongue (ET). Most studies involving HPLC and CE separations use these as selective instruments for quantification of individual substances. However we employed these techniques to provide chromatographic or electrophoretic sample profiles. These profiles are somewhat analogous to the profiles produced by the ET. Profiles from all instruments were then related to professional sensory panel evaluations using projections on latent structures (PLS) regression. It was found that all three methods allow for bitterness assessment in TCM samples in terms of human sensory panel with root mean squared errors of prediction ca. 0.9 within bitterness scale from 0 (no bitterness) to 6 (maximal bitterness). PMID- 26992501 TI - Towards field trace metal speciation using electroanalytical techniques and tangential ultrafiltration. AB - In this work we propose a trace metal speciation methodology to determine the total, free and ultrafiltered (<1 KDa) metal fractions using electrochemical methods (SCP and AGNES) and tangential ultrafiltration (UF) experiments that can easily be carried out on-site. We tested our methodology spiking Cadmium ions into two natural waters samples from Itapanhau and Sorocabinha rivers in Sao Paulo State, Brazil. The limits of detection (LOD) was 1.6*10(-9) M for the total Cd(2+) determination performed by Stripping Chronopotentiometry (SCP) in the source and acidified ultrafiltered solution and 1.9*10(-9) M for the free Cd(2+) determination using Absence of gradients and Nernstian equilibrium stripping (AGNES), using a thin mercury film electrode. The total metal determination was performed by SCP in acidified samples and the results compared with graphite furnace atomic absorption spectroscopy (GF-AAS). The SCP results were adequate with a 96% of recovery from the known metal spike for the 12 samples tested. For the Itapanhau sample the free metal determined by AGNES and the ultrafiltered fraction are identical, while for the Sorocabinha the free metal in the source is significantly smaller than the ultrafiltered fraction, indicating that this sample must be rich in metal complexes with small inorganic ligands that are able to permeate the 1kDa membrane. The proposed metal speciation methodology validated in the laboratory combining UF and SCP/AGNES is able to be used in on site experiments providing valid information regarding the total and free metal concentrations and additionally some insight on the role of small inorganic ligands to the metal complexation. PMID- 26992502 TI - Characterization of oncogene-induced metabolic alterations in hepatic cells by using ultrahigh performance liquid chromatography-tandem mass spectrometry. AB - Elucidation of altered metabolic pathways by using metabolomics may open new avenues for basic research on disease mechanisms and facilitate the development of novel therapeutic strategies. Here, we report the development of ultrahigh performance liquid chromatography-tandem mass spectrometry-based metabolomics platform with capability of measuring both cationic and anionic intermediates in cellular metabolism. The platform was established based on the hydrophobic ion pairing interaction chromatography coupled with tandem mass spectrometry in multiple reaction monitoring (MRM) mode. The MRM transitions were created and optimized via energy-resolved collision-induced dissociation experiments, serving as an essential reference point for the quantification and identification. For chromatographic separation, application of hydrophobic ion-pairing interaction led to dramatic enhancement on retention of water-soluble metabolites and provision of good peak shapes. Two volatile ion-pairing reagents, namely heptafluorobutyric acid and tributylamine, were used with dedicated C18 columns as complementary separation systems coupled with the MRM analysis, allowing measurement of the metabolites of interest at nanomolar levels. The developed platform was successfully applied to investigate the altered metabolism in hepatic cells with over-expression of an oncogene, thus can provide important information on the rewired metabolism. PMID- 26992503 TI - Rapid determination of acid herbicides in soil by liquid chromatography with tandem mass spectrometric detection based on dispersive solid phase extraction. AB - This study determined twenty six the highly sensitive phenoxy, pyridines, aliphatic and aromatic acid compounds in soil with a liquid chromatography tandem mass spectrometry. The samples were prepared by modified quick, easy, cheap, effective, rugged and safe (QuEChERS) analytical procedure in solid samples. Herbicides extraction effectiveness was evaluated at three different spiking levels (0.01, 0.1 and 1.0 mg kg(-1)). Fourteen different dispersive solid-phase extraction (d-SPE) sorbents in clean-up step were tested. The QuEChERS protocol with acidic alumina provided the highest number of pesticides with recoveries in the 70-120% range. The soil matrix effect was evaluated and for the majority of compounds were not significant, showing suppression or enhancement (+/-81-123%). The precision calculated as relative standard deviation (RSD) was below 22%. The linear relation was observed in the range 0.01-2.0 mg kg(-1) and the correlation coefficient R>0.999. The expanded measurement uncertainty was estimated as being on average, and was between 9% and 33%. The validated method was employed in the analysis of 309 real soil samples. PMID- 26992504 TI - Determination of benzene, toluene and xylene concentration in humid air using differential ion mobility spectrometry and partial least squares regression. AB - Benzene, toluene and xylene (BTX compounds) are chemicals of greatest concern due to their impact on humans and the environment. In many cases, quantitative information about each of these compounds is required. Continuous, fast-response analysis, performed on site would be desired for this purpose. Several methods have been developed to detect and quantify these compounds in this way. Methods vary considerably in sensitivity, accuracy, ease of use and cost-effectiveness. The aim of this work is to show that differential ion mobility spectrometry (DMS) may be applied for determining concentration of BTX compounds in humid air. We demonstrate, this goal is achievable by applying multivariate analysis of the measurement data using partial least squares (PLS) regression. The approach was tested at low concentrations of these compounds in the range of 5-20 ppm and for air humidity in a range 0-12 g/kg. These conditions correspond to the foreseeable application of the developed approach in occupational health and safety measurements. The average concentration assessment error was about 1 ppm for each: benzene, toluene and xylene. We also successfully determined water vapor content in air. The error achieved was 0.2 g/kg. The obtained results are very promising regarding further development of DMS technique as well as its application. PMID- 26992505 TI - Implementation of a new integrated d-lactic acid biosensor in a semiautomatic FIA system for the simultaneous determination of lactic acid enantiomers. Application to the analysis of beer samples. AB - An integrated amperometric d-lactic acid biosensor involving a gold film deposited by sputtering on a stainless steel disk electrode where the enzymes D lactic acid dehydrogenase (DLDH) and diaphorase (DP) as well as the redox mediator tetrathiafulvalene (TTF) are coimmobilized by using a dialysis membrane, is reported in this work. Amperometry in stirred solutions at a detection potential of +0.15 V (vs Ag/AgCl reference electrode) provided a linear calibration plot for D-lactic acid over the 1.0*10(-4) to 3.8*10(-3) g L(-1) concentration range, with a limit of detection of 3.1*10(-5) g L(-1). The usefulness of the biosensor was demonstrated by determining D-lactic acid in beer samples with good results. Additionally, the biosensor was implemented together with a commercial L-lactic amperometric biosensor in a semiautomatic flow injection analysis (FIA) system able to perform a rapid and simple stereo specific determination of D- and D-lactic without a previous separation step. The operational characteristics of the biosensors under flow conditions were evaluated and its applicability was demonstrated through the simultaneous determination of both enantiomers in beer samples. PMID- 26992507 TI - Simultaneous analysis of carbohydrates and organic acids by HPLC-DAD-RI for monitoring goat's milk yogurts fermentation. AB - During yogurt manufacture, the lactose fermentation and organic acid production can be used to monitor the fermentation process by starter cultures and probiotic bacteria. In the present work, a simple, sensitive and reproducible high performance liquid chromatography with dual detectors, diode array detector and refractive index was validated by simultaneous analysis of carbohydrates and organic acids in goat milk yogurts. In addition, pH and bacterial analysis were performed. Separation of all the compounds was performed on an Aminex HPX-87H column (300*7.8 mm, 9 um) utilizing a 3 mmol L(-1) sulfuric acid aqueous mobile phase under isocratic conditions. Lactose, glucose, galactose, citric, lactic and formic acids were used to evaluate the following performance parameters: selectivity, linearity, precision, limit of detection (LOD), limit of quantification (LOQ), decision limits (CCalpha), detection capabilities (CCbeta), recovery and robustness. For the method application a six goat milk yogurts were elaborated: natural, probiotic, prebiotic, symbiotic, cupuassu fruit pulp, and probiotic with cupuassu fruit pulp. The validated method presented an excellent selectivity with no significant matrix effect, and a broad linear study range with coefficients of determination higher than 0.995. The relative standard deviation was lower than 10% under repeatability and within-laboratory reproducibility conditions for the studied analytes. The LOD of the method was defined from 0.001 to 0.003 ug g(-1), and the LOQ from 0.003 to 0.013 ug g(-1). The CCalpha was ranged from 0.032 to 0.943 ug g(-1), and the CCbeta from 0.053 to 1.604 ug g(-1). The obtained recovery values were from 78% to 119%. In addition, the method exhibited an appropriate robustness for all parameter evaluated. Base in our data, it was concluded that the performance parameters demonstrated total method adequacy for the detection and quantification of carbohydrates and organic acids in goat milk yogurts. The application of the method was successfully applied to monitoring different goat milk yogurts during fermentation. PMID- 26992506 TI - Highly selective and sensitive fluorescent probe for the detection of nitrite. AB - A simple and reliable fluorescent nitrite (NO2(-)) probe, 2-(1H-phenanthro[9,10 d] imidazol-2-yl)aniline (PA), was rationally developed based on a novel NO2(-) mediated diazozation and subsequent cyclization. The new sensing mechanism of the probe was confirmed by using NMR, IR spectra, control experiments and DFT calculations. The synthesized probe showed low pH dependence, fast and highly selective fluorescence response to NO2(-) over other species. Under the optimized conditions, the linear response of the probe toward NO2(-) was in the range of 0.1-10 MUM with a low detection limit of 4.3*10(-8) M. Moreover, PA was successfully applied for the determination of NO2(-) in environmental samples and food products. PMID- 26992508 TI - Enhanced chemiluminescence of carminic acid-permanganate by CdS quantum dots and its application for sensitive quenchometric flow injection assays of cloxacillin. AB - A novel chemiluminescence (CL) system is introduced based on the oxidation of carminic acid by KMnO4 in acidic conditions. CdS quantum dots (QDs) were synthesized using a facile hydrothermal method which efficiently enhanced the intensity of the CL system. A possible mechanism for the proposed system is presented using the kinetic curves, CL spectra, photoluminescence (PL), and ultraviolet-visible (UV-Vis) analysis. The emission intensity of the KMnO4 carminic acid-CdS QDs system was quenched in the presence of a trace level of cloxacillin. Based on this quenching effect, a novel and sensitive flow injection CL method was developed for determining cloxacillin concentrations. At optimal experimental conditions, the decreased CL intensity had a good linear relation with the cloxacillin concentration in the range of 0.008 to 22.0 mg L(-1). The detection limit (3sigma) was 5.8 ug L(-1). The precision of the method was calculated by analyzing samples containing 4.0 mg L(-1) of cloxacillin (n=11), and the relative standard deviations (RSD%) were 2.08%. The feasibility of the method is also demonstrated for determining cloxacillin concentrations in environmental water samples and a pharmaceutical formulation. PMID- 26992509 TI - DoE optimization of a mercury isotope ratio determination method for environmental studies. AB - By using the experimental design (DoE) technique, we optimized an analytical method for the determination of mercury isotope ratios by means of cold-vapor multicollector ICP-MS (CV-MC-ICP-MS) to provide absolute Hg isotopic ratio measurements with a suitable internal precision. By running 32 experiments, the influence of mercury and thallium internal standard concentrations, total measuring time and sample flow rate was evaluated. Method was optimized varying Hg concentration between 2 and 20 ng g(-1). The model finds out some correlations within the parameters affect the measurements precision and predicts suitable sample measurement precisions for Hg concentrations from 5 ng g(-1) Hg upwards. The method was successfully applied to samples of Manila clams (Ruditapes philippinarum) coming from the Marano and Grado lagoon (NE Italy), a coastal environment affected by long term mercury contamination mainly due to mining activity. Results show different extents of both mass dependent fractionation (MDF) and mass independent fractionation (MIF) phenomena in clams according to their size and sampling sites in the lagoon. The method is fit for determinations on real samples, allowing for the use of Hg isotopic ratios to study mercury biogeochemical cycles in complex ecosystems. PMID- 26992510 TI - Electrospun fibrous thin film microextraction coupled with desorption corona beam ionization-mass spectrometry for rapid analysis of antidepressants in human plasma. AB - Appropriate sample preparations prior to analysis can significantly enhance the sensitivity of ambient ionization techniques, especially during the enrichment or purification of analytes in the presence of complex biological matrix. Here in, we developed a rapid analysis method by the combination of thin film microextraction (TFME) and desorption corona beam ionization (DCBI) for the determination of antidepressants in human plasma. Thin films used for extraction consisted of sub-micron sized highly ordered mesoporous silica-carbon composite fibers (OMSCFs), simply prepared by electrospinning and subsequent carbonization. Typically, OMSCFs thin film was immersed into the diluted plasma for extraction of target analytes and then directly subjected to the DCBI-MS for detection. Size exclusion effect of mesopores contributed to avoid of the protein precipitation step prior to extraction. Mass transfer was benefited from high surface-to-volume ratio which is attributed to macroporous network and ordered mesostructures. Moreover, the OMSCFs provided mixed-mode hydrophobic/ion-exchange interactions towards target analytes. Thus, the detection sensitivity was greatly improved due to effective enrichment of the target analytes and elimination of matrix interferences. After optimization of several parameters related to extraction performance, the proposed method was eventually applied for the determination of three antidepressants in human plasma. The calibration curves were plotted in the range of 5-1000 ng/mL with acceptable linearity (R(2) >0.983). The limits of detection (S/N=3) of three antidepressants were in ranges of 0.3-1 ng/mL. Reproducibility was achieved with RSD less than 17.6% and the relative recoveries were in ranges of 83.6-116.9%. Taken together, TFME-DCBI-MS method offers a powerful capacity for rapid analysis to achieve much-improved sensitivity. PMID- 26992511 TI - Sensitive and label-free quantification of cellular biothiols by competitive surface-enhanced Raman spectroscopy. AB - A label-free surface-enhanced Raman spectroscopy (SERS)-based method for the rapid quantification detection of cellular biothiols at picomolar levels was developed by using a mechanism of binary competitive adsorption to regulate the plasmon coupling behavior of gold nanoparticles (Au NPs). 4,4'-Dipyridyl (Dpy), a small organic ligand with two symmetrically located pyridine rings, was used to shorten the inter-particle space and generate a multitude of "hot spots", which in turn amplified the fingerprint signals of Dpy molecules. When biothiols were introduced into the Dpy-containing solution of Au NPs, they competitively adsorbed to the metal surface through the much stronger S-Au linkage, leading to the disaggregation of Au NPs and SERS quenching of Dpy molecules. The change of SERS responses was quantitatively related to biothiols added to the solution, and the detection limit down to 0.14 pM for GSH was facilely achieved without any pre concentration. The total assay time, including data analysis was within 8 min. Finally, the SERS-based method was successfully applied to measure cellular biothiols, indicating its potential applicability in biological and biomedical research. PMID- 26992512 TI - Facile synthesis of magnetic hypercrosslinked polystyrene and its application in the magnetic solid-phase extraction of sulfonamides from water and milk samples before their HPLC determination. AB - In this study, a novel magnetic solid-phase extraction (MSPE) sorbent, magnetic hypercrosslinked polystyrene (HCP/Fe3O4), was prepared and used for preconcentration of four sulfonamides (sulfamethoxypyridazine, sulfamethazine, sulfamethoxazole and sulfachloropyridazine) from natural water and milk samples. This material was prepared by sorption of pre-synthesized Fe3O4 nanoparticles (NPs) onto HCP. A number of sorbents with varying Fe3O4NPs content were prepared, and their structural, magnetic and sorption properties were studied. Various experimental parameters affecting the extraction efficiencies such as the amount of the magnetic nanocomposite, extraction time, pH of the sample solution and desorption conditions were studied and optimized. Under the optimal conditions, a convenient and efficient method for the determination of sulfonamides in water and milk samples was developed by combining MSPE and high-performance liquid chromatography with amperometric detection. The results showed that the recoveries of these compounds were in the range of 84-105% with the relative standard deviations ranging between 3% and 10%; the limit of detection were in the range of 0.21-0.33 ng mL(-1) for water and 2.0-2.5 ng mL(-1) for milk. PMID- 26992513 TI - Inorganic arsenic speciation by differential pulse anodic stripping voltammetry using thoria nanoparticles-carbon paste electrodes. AB - Two novel thoria (ThO2) nanoparticles-carbon paste electrodes were used to evaluate an anodic stripping voltammetric method for the direct determination of arsenite and total inorganic arsenic (arsenite plus arsenate) in water samples. The effect of Ag((I)), Cu((II)), Hg((II)), Sb((III)) and Se((IV)) ions on the electrochemical response of arsenic was assayed. The developed electroanalytical method offers a rapid procedure with improved analytical characteristics including good repeatability (3.4%) at low As((III)) concentrations, high selectivity, lower detection limit (0.1 MUg L(-1)) and high sensitivity (0.54 MUA MUg(-1) L). The analytical capability of the optimized method was demonstrated by the determination of arsenic in certified reference materials (trace elements in natural water, trace elements in water and coal fly ash). PMID- 26992514 TI - Determination of strontium-90 from direct separation of yttrium-90 by solid phase extraction using DGA Resin for seawater monitoring. AB - It is important for public safety to monitor strontium-90 in aquatic environments in the vicinity of nuclear related facilities. Strontium-90 concentrations in seawater exceeding the background level have been observed in accidents of nuclear facilities. However, the analytical procedure for measuring strontium-90 in seawater is highly demanding. Here we show a simple and high throughput analytical technique for the determination of strontium-90 in seawater samples using a direct yttrium-90 separation. The DGA Resin is used to determine the abundance of strontium-90 by detecting yttrium-90 decay (beta-emission) in secular equilibrium. The DGA Resin can selectively collect yttrium-90 and remove naturally occurring radionuclides such as (40)K, (210)Pb, (214)Bi, (238)U, and (232)Th and anthropogenic radionuclides such as (140)Ba, and (140)La. Through a sample separation procedure, a high chemical yield of yttrium-90 was achieved at 95.5+/-2.3%. The result of IAEA-443 certified seawater analysis (107.7+/-3.4 mBq kg(-1)) was in good agreement with the certified value (110+/-5 mBq kg(-1)). By developed method, we can finish analyzing 8 samples per day after achieving secular equilibrium, which is a reasonably fast throughput in actual seawater monitoring. By processing 3 L of seawater sample and applying a counting time of 20 h, minimum detectable activity can be as low as 1.5 mBq kg(-1), which could be applied to monitoring for the contaminated marine environment. Reproducibility was found to be 3.4% according to 10 independent analyses of natural seawater samples from the vicinity of the Fukushima Daiichi Nuclear Power Plant in September 2013. PMID- 26992515 TI - DNA-gold nanoparticles network based electrochemical biosensors for DNA MTase activity. AB - In this work, a highly sensitive electrochemical DNA methyltransferase (MTase) activity assay was fabricated with DNA-gold nanoparticles (Au NPs) network as signal amplification unit and an easy assembly method by the linkage of benzenedithiol bridge. By two complementary AuNPs modified single-stranded DNA, DNA-gold nanoparticles network was self-assembled. With the linkage of benzenedithiol bridge, the DNA network structure was immobilized on the surface of gold electrode through the covalent Au-S bond. In the presence of Dam MTase, the special sites of DNA-AuNPs network were methylated and could not be digested by restriction endonuclease Mbo I. Thus the loaded electrochemical indicator Methylene blue (MB) was MB molecules still remained on the DNA-Au NPs network. The electrochemical response depended on the methylated degree, which could be used to detect MTase activity. By the differential pulse voltammetry (DPV), it was demonstrated that a linear relationship between the DPV response and logarithm of Dam concentration ranged from 0.075 to 30 U/mL, achieving a low detection limit of 0.02 U/mL. The use of benzenedithiol avoided the direct incubation of the solid electrode with the capture DNA probe under complex and harsh conditions. Therefore the immobilization of DNA-AuNPs network was easy to be carried out, which is favorable for the specially high stability and reproducibility of the electrochemical biosensor. PMID- 26992516 TI - Highly sensitive wavelength-dependent nonaqueous capillary electrophoresis for simultaneous screening of various synthetic organic dyes. AB - A novel multi-wavelength nonaqueous capillary electrophoresis (MW-NACE) technique based on wavelength-dependent laser-induced fluorescence (LIF) detection was investigated for the simultaneous screening of various synthetic organic dyes. Multi-wavelength excitation light sources were utilized to excite different organic dyes [e.g., 543 nm for crystal violet (CV), methyl violet B (MVB), methyl violet B base (MBB), rhodamine 6G (R6G), and rhodamine B base (RBB); 635 nm for nile blue A (NBA) and methylene blue (MB)] simultaneously. Using a nonaqueous buffer system composed of 15 mM sodium borate and 835 mM acetic acid in 100% ethanol (pH=5.4), all dyes were analyzed within 15 min with excellent resolution (R>=4.0) under an electric field of 500 V/cm. Calibration curves showed excellent linearity with square of correlation coefficients (r(2)) greater than 0.9908 over wide dynamic ranges of 0.4-50 MUM for CV, 0.8-50 MUM for MVB, 1.5-50 MUM for MBB, 0.08-5 nM for R6G, 0.06-10 MUM for MB, 0.02-10 MUM for NBA, and 0.13-10 pM for RBB. The detection limits (S/N=3) of 40 fM to 0.5 MUM were 10-200,000 times lower than those of previous detection methods. While adjacent peaks were not well distinguished with baseline separation in a single capillary, the devised technique was faster and more sensitive than conventional aqueous and nonaqueous CE approaches, thereby enabling the quantitative analysis of various dyes based on wavelength-dependent fluorescence detection with different excitation wavelengths. PMID- 26992517 TI - Emulsion-cryogelation technique for fabricating a versatile toolbox of hierarchical polymeric monolith and its application in chromatography. AB - A novel poly (glycidyl methacrylate-co-ethylene dimethacrylate) monolith has been fabricated via the environmental friendly cryogelation-emulsion technique. The polymerization process is assisted by self-assembly of typical tri-block copolymer Pluronic F127 at sub-zero temperature using ice crystal as template, which can avoid consumption of organic porogenic solvents and thermal unstability of emulsion system. The developed monolith possesses hierarchical networks, which is confirmed by nitrogen adsorption measurement, mercury intrusion porosimetry, scanning electron microscopy and permeability testing. Further, the effect of the amounts of Pluronic F127 on the microstructure has been investigated. Moreover, the prepared polymer monolith undergoes acidic hydrolysis of epoxy groups into hydroxyl groups on the surface and its liquid chromatographic performance is explored by separating model analytes. The results indicate that the unique porous polymer monolith with hierarchical networks could be prepared via an organic porogen-free approach and used for analysis of polar and nonpolar molecules, extending the application of cryogelation-emulsion technique and methacrylate-based monolith. PMID- 26992518 TI - Potential reference measurement procedures for PBDE in surface water at levels required by the EU Water Frame Directive. AB - Polybrominated diphenylethers (PBDE), used as flame retardants, are named as priority substances in the Directive 2000/60/EC of the European parliament and of the council establishing a framework for Community action in the field of water policy. An annual average environmental quality standard (EQS) for inland surface waters of 0.0005 ug/L (0.0002 ug/L for other surface waters) for PBDE congeners involved in the technical penta-PBDE mixtures containing PBDE with five bromine atoms has been established. The directives focus especially on the congeners PBDE 28, 47, 99, 100, 153 and 154 contained in the penta-PBDE mixture. Up to now, no reference measurement procedures have been established reaching the limits of quantification (LOQs) and the associated uncertainties as defined in the directives with results traceable to the SI. Within a recent European project on metrology, different approaches for the traceable quantification of PBDE, based on liquid/liquid or solid phase extraction followed by the detection with gas chromatography coupled to either inductively coupled plasma mass spectrometry or triple quadrupole mass spectrometry, were investigated and the related LOQs and expanded uncertainties of the results were compared. A complete uncertainty budget for each method was estimated according to the Guide to the Expression of Uncertainty in Measurement (GUM). All presented analytical procedures can serve as reference measurement procedures regarding the LOQs and their associated expanded uncertainties for monitoring the six priority PBDEs named above. LOQs as low as 0.026 ng/kg with an associated expanded uncertainty of 0.002 ng/kg could be achieved. PMID- 26992519 TI - Influence of the linking spacer length and type on the enantioseparation ability of beta-cyclodextrin functionalized monoliths. AB - In order to investigate the effect of the linking spacer on the enantioseparation ability of beta-cyclodextrin (beta-CD) functionalized polymeric monoliths, three beta-CD-functionalized organic polymeric monoliths with different spacer lengths were prepared by using three amino-beta-CDs, i.e. mono-6-amino-6-deoxy-beta-CD, mono-6-ethylenediamine-6-deoxy-beta-CD, mono-6-hexamethylenediamine-6-deoxy-beta CD, as starting materials. These amino-beta-CDs reacted with glycidyl methacrylate to produce functional monomers which were then copolymerized with ethylene dimethacrylate. The enantioseparation ability of the three monoliths was evaluated using 14 chiral acidic compounds, including mandelic acid derivatives, nonsteroidal anti-inflammatory drugs, N-derivatized amino acids, and chiral herbicides under optimum chromatographic conditions. Notably, the poly(GMA-NH2 beta-CD-co-EDMA) column provides higher enantioresolution and enantioselectivity than the poly(GMA-EDA-beta-CD-co-EDMA) and poly(GMA-HDA-beta-CD-co-EDMA) columns for most tested chiral analytes. Furthermore, the enantioseparation performance of triazole-linker containing monoliths was compared to that of ethylenediamine linker containing monoliths. The results indicate that the enantioselectivity of beta-CD monolithic columns is strongly related to the length and type of spacer tethering beta-CD to the polymeric support. PMID- 26992520 TI - Improved sensitivity of lateral flow assay using paper-based sample concentration technique. AB - Lateral flow assays (LFAs) hold great promise for point-of-care testing, especially in resource-poor settings. However, the poor sensitivity of LFAs limits their widespread applications. To address this, we developed a novel device by integrating dialysis-based concentration method into LFAs. The device successfully achieved 10-fold signal enhancement in Human Immunodeficiency Virus (HIV) nucleic acid detection with a detection limit of 0.1 nM and 4-fold signal enhancement in myoglobin (MYO) detection with a detection limit of 1.56 ng/mL in less than 25 min. This simple, low-cost and portable integrated device holds great potential for highly sensitive detection of various target analytes for medical diagnostics, food safety analysis and environmental monitoring. PMID- 26992522 TI - Rapid separation of non-polar and weakly polar analytes with metal-organic framework MAF-5 coated capillary column. AB - Metal-organic frameworks (MOFs) have attracted widespread attention due to their unique characters such as high surface area, high thermal and chemical stability, diverse structure topology and tunable pore size. The study first exploited a porous metal organic framework MAF-5 ([Zn[(eim)2], Heim=2-ethylimidazole) as stationary phase for gas chromatography by a novel dynamic coating method. The column efficiency of the 184 silicone@MAF-5 capillary column was up to 9045 plates m(-1) for benzene. The column is very promising for the rapid separation of polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs). And the column showed good reproducibility, retention time, peak area, high resolution, and a wide linear range. The determined thermodynamic parameters and chromatographic retention of all probe molecules on the 184 silicone@MAF-5 column showed the separation of analytes is a complex balance of thermodynamic and kinetic factors. PMID- 26992521 TI - Coatings of molecularly imprinted polymers based on polyhedral oligomeric silsesquioxane for open tubular capillary electrochromatography. AB - Polyhedral oligomeric silsesquioxane (POSS) was successfully applied, for the first time, to prepare imprinted monolithic coating for capillary electrochromatography. The imprinted monolithic coating was synthesized with a mixture of PSS-(1-Propylmethacrylate)-heptaisobutyl substituted (MA 0702), S amlodipine (template), methacrylic acid (functional monomer), and 2 methacrylamidopropyl methacrylate (crosslinker), in a porogenic mixture of toluene-isooctane. The influence of synthesis parameters on the imprinting effect and separation performance, including the amount of MA 0702, the ratio of template to monomer, and the ratio of monomer to crosslinker, was investigated. The greatest resolution for enantiomers separation on the imprinted monolithic column prepared with MA 0702 was up to 22.3, about 2 times higher than that prepared in absence of the POSS. Column efficiency on the POSS-based MIP coatings was beyond 30,000 plate m(-1). The comparisons between MIP coating synthesized with the POSS and without the POSS were made in terms of selectivity, column efficiency, and resolution. POSS-based MIP capillaries with naproxen or zopiclone was also prepared and separation of enantiomers can be achieved. PMID- 26992523 TI - Fluorescent probes for "off-on" highly sensitive detection of Hg2+ and L-cysteine based on nitrogen-doped carbon dots. AB - Fluorescent nitrogen-doped carbon dots (NCDs) were synthesized by a facile, and low-cost one-step hydrothermal strategy using citric acid as carbon source and ammonia solution as nitrogen source for the first time. The obtained NCDs show stable blue fluorescence with a high quantum yield of 35.4%, along with the fluorescence lifetime of ca. 6.75 ns. Most importantly, Hg(2+) can completely quench the fluorescence of NCDs as a result of the formation of a non-fluorescent stable NCDs-Hg(2+) complex. Static fluorescence quenching towards Hg(2+) is proved by the Stern-Volmer equation, ultraviolet-visible absorption spectra, temperature dependent quenching and fluorescence lifetime measurements. Subsequently, the fluorescence of the NCDs-Hg(2+) system is completely recovered with the addition L-cysteine (L-Cys) owing to the dissociation of NCDs-Hg(2+) complex to form a more stable Hg(2+)-L-Cys complex by Hg(2+)-S bonding. Therefore, such NCDs can be used as an effective fluorescent "turn-off" probe for rapid, rather highly selective and sensitive detection of Hg(2+), with a limit of detection (LOD) as low as 1.48 nM and a linear detection range of 0-10 MUM. Interestingly, NCDs-Hg(2+) system can be conveniently employed as a fluorescent "turn-on" sensor for highly selective and sensitive detection of L-Cys with a low LOD of 0.79 nM and a wide linear detection range of 0-50 MUM. Further, the sensitivity of NCDs to Hg(2+) is preserved in tap water with a LOD of 1.65 nM and a linear detection range of 0-10 MUM. PMID- 26992525 TI - A batch injection analysis system with square-wave voltammetric detection for fast and simultaneous determination of naphazoline and zinc. AB - In this work, a batch-injection analysis system with square-wave voltammetric (BIA-SWV) detection was applied for the first time to the simultaneous determination of inorganic (zinc) and organic (naphazoline) species. Both compounds were detected in a single run (70 injections h(-1)) with a small injection volume (~100 uL). The calibration curves exhibited linear response range between 3.0 and 21.0 MUmol L(-1) (r=0.999) for naphazoline and between 10.0 and 60.0 MUmol L(-1) (r=0.992) for zinc. The detection limits were 0.13 and 0.04 MUmol L(-1) for zinc and naphazoline, respectively. Good reproducibility was achieved for multiple measurements of a solution containing both species (RSD<1.0%; n=20). The results obtained with the BIA-SWV method for the simultaneous determination of naphazoline and zinc were compared to those obtained by HPLC (naphazoline) and by FAAS (zinc); no statistically significant differences were observed (95% confidence level). PMID- 26992524 TI - High specific surface gold electrode on polystyrene substrate: Characterization and application as DNA biosensor. AB - In the past decades, many efforts have been made to improve the sensitivity and specificity of electrochemical DNA biosensors. However, it is still strongly required to develop disposable and reliable DNA biosensors for wide and practical application. In this article, we reported superior electrochemical properties of an integrated plastic-gold electrode (PGE) fabricated in-house by chemical plating on polystyrene substrate. PGEs were found having extremely high capacity of DNA immobilization compared with gold electrodes fabricated by standard sputtering based photolithography. Unique nano-structured surface was observed on PGEs through morphology techniques, which would to some extend give an explanation to higher capacity of DNA immobilization on PGEs. A probable mechanism of carboxylic acid produced on polystyrene substrate after exposure to UV irradiation was proposed and discussed for the first time. This biosensor was applied to detection and manipulate of DNA hybridization. Detection limit of 7.2*10(-11) M and 1-500 nM of linearity range was obtained. PMID- 26992526 TI - Label-free and selective sensing of uric acid with gold nanoclusters as optical probe. AB - Clinically, the amount of uric acid (UA) in biological fluids is closely related to some diseases such as hyperuricemia and gout, thus it is of great significance to sense UA in clinical samples. In this work, red gold nanoclusters (AuNCs) with relatively high fluorescence quantum yield and strong fluorescence emission were facilely available using bovine serum albumin (BSA) as template. The fluorescence of BSA-protected AuNCs can be sensitively quenched by H2O2, which is further capable of sensing UA through the specific catalytic oxidation with uricase, since it generates stoichiometric quantity of H2O2 by-product. The proposed assay allows for the selective detection of UA in the range of 10-800 MUM with a detection limit of 6.6 MUM, which is applicable to sense UA in clinical samples with satisfactory results, suggesting its great potential for diagnostic purposes. PMID- 26992528 TI - Passive exposure to nicotine from e-cigarettes. AB - A procedure based on the use of ion mobility spectrometry (IMS), after liquid liquid microextraction (LLME), has been successfully employed for the determination of passive exposure to nicotine from cigarette and e-cigarette smoking. Nicotine has been determined in exhaled breath and oral fluids of both, active and passive smokers. The aforementioned studies, made in closed environments, evidenced that the exhaled breath after conventional blend cigarette smoke provides nicotine levels of the order of 220 ng per puff, in the case of experienced smokers, being exhaled only 32 ng in the case of e cigarettes. On the other hand, the nicotine amount in oral fluids of passive vapers was between 8 and 14 ug L(-1) lower than the average value of 38+/-14 ug L(-1) found for passive smokers of rolling tobacco and clearly lower than the 79+/-36 ug L(-1) obtained from passive smokers of classical yellow blend. This study was also placed in the frame of the verification of the e-cigarettes composition. PMID- 26992527 TI - Preparation of a Co-doped hierarchically porous carbon from Co/Zn-ZIF: An efficient adsorbent for the extraction of trizine herbicides from environment water and white gourd samples. AB - A Co-doped hierarchically porous carbon (Co/HPC) was synthesized through a facile carbonization process by using Co/ZIF-8 as the precursor. The textures of the Co/HPC were investigated by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, vibration sample magnetometry and nitrogen adsorption-desorption isotherms. The results showed that the Co/HPC is in good polyhedral shape with uniform size, sufficient magnetism, high surface area as well as hierarchical pores (micro-, meso- and macropores). To evaluate the extraction performance of the Co/HPC, it was applied as a magnetic adsorbent for the enrichment of triazine herbicides from environment water and white gourd samples prior to high performance liquid chromatographic analysis. The main parameters that affected the extraction efficiency were investigated. Under the optimum conditions, a good linearity for the four triazine herbicides was achieved with the correlation coefficients (r) higher than 0.9970. The limits of detection, based on S/N=3, were 0.02 ng/mL for water and 0.1-0.2 ng/g for white gourd samples, respectively. The recoveries of all the analytes for the method fell in the range from 80.3% to 120.6%. PMID- 26992529 TI - Determination of groundwater mercury (II) content using a disposable gold modified screen printed carbon electrode. AB - Mercury (II) measurements were performed thanks to a newly developed electrochemical method using a disposable gold modified screen printed carbon electrode. The method has a wide dynamic range (1-100 ug/L), a good accuracy and a limit of detection in compliance with WHO standards. The application of the method to several groundwater samples made it possible to identify, for the first time, mercury content higher than the recommended WHO standard value in a gold mining activity area in the northern part of Burkina Faso. The accuracy of the assay was checked by ICP/MS. PMID- 26992530 TI - Direct spectral analysis of tea samples using 266 nm UV pulsed laser-induced breakdown spectroscopy and cross validation of LIBS results with ICP-MS. AB - Tea is one of the most common and popular beverages spanning vast array of cultures all over the world. The main nutritional benefits of drinking tea are its anti-oxidant properties, presumed protection against certain cancers, inhibition of inflammation and possible protective effects against diabetes. Laser induced breakdown spectrometer (LIBS) was assembled as a powerful tool for qualitative and quantitative analysis of various brands of tea samples using 266 nm pulsed UV laser. LIBS spectra for six brands of tea samples in the wavelength range of 200-900 nm was recorded and all elements present in our tea samples were identified. The major toxic elements detected in several brands of tea samples were bromine, chromium and minerals like iron, calcium, potassium and silicon. The spectral assignment was conducted prior to the determination of concentration of each element. For quantitative analysis, calibration curves were drawn for each element using standard samples prepared in known concentration in the tea matrix. The plasma parameters (electron temperature and electron density) were also determined prior to the tea samples spectroscopic analysis. The concentration of iron, chromium, potassium, bromine, copper, silicon and calcium detected in all tea samples was between 378-656, 96-124, 1421-6785, 99-1476, 17 36, 2-11 and 92-130 mg L(-1) respectively. The limits of detection estimated for Fe, Cr, K, Br, Cu, Si, Ca in tea samples were 22, 12, 14, 11, 6, 1 and 12 mg L( 1) respectively. To further confirm the accuracy of our LIBS results, we determined the concentration of each element present in tea samples by using standard analytical technique like ICP-MS. The concentrations detected with our LIBS system are in excellent agreement with ICP-MS results. The system assembled for spectral analysis in this work could be highly applicable for testing the quality and purity of food and also pharmaceuticals products. PMID- 26992531 TI - Fast and simple determination of perfluorinated compounds and their potential precursors in different packaging materials. AB - A simple and fast analytical method for the determination of fourteen perfluorinated compounds (PFCs), including three perfluoroalkylsulfonates (PFSAs), seven perfluorocarboxylic acids (PFCAs), three perfluorophosphonic acids (PFPAs) and perfluorooctanesulfonamide (PFOSA) and ten potential precursors, including four polyfluoroalkyl phosphates (PAPs), four fluorotelomer saturated acids (FTCAs) and two fluorotelomer unsaturated acids (FTUCAs) in different packaging materials was developed in the present work. In order to achieve this objective the optimization of an ultrasonic probe-assisted extraction (UPAE) method was carried out before the analysis of the target compounds by liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-QqQ-MS/MS). 7 mL of 1 % acetic acid in methanol and a 2.5-min single extraction cycle were sufficient for the extraction of all the target analytes. The optimized analytical method was validated in terms of recovery, precision and method detection limits (MDLs). Apparent recovery values after correction with the corresponding labeled standard were in the 69-103 % and 62-98 % range for samples fortified at 25 ng/g and 50 ng/g concentration levels, respectively and MDL values in the 0.6-2.2 ng/g range were obtained. The developed method was applied to the analysis of plastic (milk bottle, muffin cup, pre-cooked food wrapper and cup of coffee) and cardboard materials (microwave popcorn bag, greaseproof paper for French fries, cardboard box for pizza and cinema cardboard box for popcorn). To the best of our knowledge, this is the first method that describes the determination of fourteen PFCs and ten potential precursors in packaging materials. Moreover, 6:2 FTCA, 6:2 FTUCA and 5:3 FTCA analytes were detected for the first time in microwave popcorn bags. PMID- 26992532 TI - Classifying patients in peritoneal dialysis by mass spectrometry-based profiling. AB - Protein equalization with dithiothreitol, protein depletion with acetonitrile and the entire proteome were assessed in conjunction with matrix assisted laser desorption ionization time of flight mass spectrometry-based profiling for a fast and effective classification of patients with renal insufficiency. Two case groups were recruited as proof of concept, patients with chronic glomerulonephritis and diabetic nephropathy. Two key tools were used to develop this approach: protein concentration with centrifugal concentrator tubes with 10 KDa cut-off membranes and chemical assisted protein equalization with dithiothreitol or chemical assisted protein depletion with acetonitrile. In-house developed software was used to apply principal component analysis and hierarchical clustering to the profiles obtained. The results suggest that chemical assisted protein equalization with dithiothreitol is a methodology more robust than the other two ones, as the patients were well grouped by principal component analysis or by hierarchical clustering. PMID- 26992533 TI - Determination of elemental impurities in poly(vinyl chloride) by inductively coupled plasma optical emission spectrometry. AB - In this work, a method for poly(vinyl chloride) (PVC) analysis by inductively coupled plasma optical emission spectrometry (ICP-OES) was developed. Samples were digested by microwave-induced combustion (MIC) and thirteen elements (Ba, Cd, Co, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sr, V and Zn) were determined by ICP-OES. Operational conditions of MIC were investigated allowing quantitative determination of all the analytes and suitable results were achieved using a 3 mol L(-1) HNO3 solution. Microwave-assisted wet digestion (MAWD) using closed quartz vessels and a single reaction chamber microwave digestion system (MAWD SRC), were also evaluated for PVC digestion for results comparison. All the evaluated sample preparation methods were considered suitable for PVC digestion but MIC was preferable due to the possibility of using diluted HNO3 instead of concentrated reagents and due to the better digestion efficiency. The residual carbon content (RCC) in digests obtained by MIC was significantly lower in comparison with the values obtained after MAWD and by MAWD-SRC. Accuracy for the proposed method was better than 94% for all analytes by comparison of results with those obtained by neutron activation analysis (NAA). Using MIC, it was possible to digest a relatively high sample mass (500 mg) and up to 8 samples in less time (25 min) in comparison with MAWD and MAWD-SRC (about 60 min for both methods). The efficiency of digestion by MIC was higher 99% and lower limits of detection (as low as 0.1 ug g(-1)) were obtained avoiding the use of concentrated acids that is of great concern according to the current green chemistry recommendations. PMID- 26992534 TI - Mesoporous silica based MCM-41 as solid-phase extraction sorbent combined with micro-liquid chromatography-quadrupole-mass spectrometry for the analysis of pharmaceuticals in waters. AB - This paper reports the first application of the silica based mesoporous material MCM-41 as a sorbent in solid phase extraction, to pre-concentrate pharmaceuticals of very different polarity (atenolol, nadolol, pindolol, timolol, bisoprolol, metoprolol, betaxolol, ketoprofen, naproxen, ibuprofen, diclofenac, tolfenamic acid, flufenamic acid and meclofenamic acid) in surface waters. The analytes were extracted from 100mL water samples at pH 2.0 (containing 10(-3) mol/L of sodium chloride) by passing the solution through a cartridge filled with 100 mg of MCM 41. Following elution, the pharmaceuticals were determined by micro-liquid chromatography and triple quadrupole-mass spectrometry. Two selected reaction monitoring transitions were monitored per compound, the most intense one being used for quantification and the second one for confirmation. Matrix effect was found in real waters for most analytes and was overcome using the standard addition method, which compared favorably with the matrix matched calibration method. The detection limits in solvent (acetonitrile:water 10:90, v/v) ranged from 0.01 to 1.48 MUg/L and in real water extracts from 0.10 to 3.85 MUg/L (0.001 0.0385 MUg/L in the water samples). The quantitation limits in solvent were in the range 0.02-4.93 MUg/L, whereas in real water extracts were between 0.45 and 10.00 MUg/L (0.0045 and 0.1000 MUg/L in the water samples). When ultrapure water samples were spiked at two concentration levels of each pharmaceutical (0.1 and 0.2 MUg/L) and quantified using solvent based calibration graphs, recoveries were near 100%. However, recoveries for most pharmaceuticals were comparable or better than de described above, when river water samples (spiked at the same concentration levels) were quantified by the standard addition method and slightly worse using the matrix matched calibration method. Five real samples (two rivers, one dam and two fountain water samples) were analyzed by the developed method, atenolol, timolol, betaxolol, nadolol and diclofenac being found in some of them, at levels higher than their quantitation limits. PMID- 26992535 TI - Calixarene ionic liquid modified silica gel: A novel stationary phase for mixed mode chromatography. AB - A novel calixarene ionic liquid functionalized silica material was synthesized by the preparation of a new calixarene monomer and its grafting on mercaptopropyl modified silica gel. The material was characterized by infrared spectra, elemental analysis, and thermogravimetric analysis. To explore the retention mechanism of the stationary phase, linear solvation energy relationships (LSER) equation as an effective mathematical model was used. In addition to this, the distinct separation mechanisms were outlined by selected examples of chromatographic separations in the different modes. In reversed-phase liquid chromatography, this new stationary phase presented specific chromatographic performance when evaluated using alkylbenzenes, PAHs and phenols as solutes. Due to the existing polar functional groups, this stationary phase can also be used in hydrophilic interaction chromatography, six nucleosides and four ginsenosides were separated successfully in hydrophilic mode. Furthermore, anions can be separated on the column in anion exchange mode. Thus, this new material was can be applied as a new kind of mixed-mode stationary phase in liquid chromatography, which allows an exceptionally flexible adjustment of retention and selectivity by tuning the experimental conditions. PMID- 26992537 TI - Colorimetric detection based on localised surface plasmon resonance of gold nanoparticles: Merits, inherent shortcomings and future prospects. AB - Localised surface plasmon resonance (LSPR) of gold nanoparticles (AuNPs) has been exploited for two decades in analytical science and has proven to be a powerful tool for the detection of various kinds of substances including small molecules, ions, macro biomolecules and microbes. Detection can be performed by visual colour change observations, photometry or resonance light scattering. A wide range of applications have been studied in the areas of environmental, pharmaceutical and biological analysis and clinical diagnosis. In this article, some fundamental aspects and important applications involving LSPR of AuNPs are reviewed. Several inherent shortcomings of these techniques and possible strategies to circumvent them are discussed. PMID- 26992536 TI - Simultaneous determination of estrogens (ethinylestradiol and norgestimate) concentrations in human and bovine serum albumin by use of fluorescence spectroscopy and multivariate regression analysis. AB - The endocrine disruption property of estrogens necessitates the immediate need for effective monitoring and development of analytical protocols for their analyses in biological and human specimens. This study explores the first combined utility of a steady-state fluorescence spectroscopy and multivariate partial-least-square (PLS) regression analysis for the simultaneous determination of two estrogens (17alpha-ethinylestradiol (EE) and norgestimate (NOR)) concentrations in bovine serum albumin (BSA) and human serum albumin (HSA) samples. The influence of EE and NOR concentrations and temperature on the emission spectra of EE-HSA EE-BSA, NOR-HSA, and NOR-BSA complexes was also investigated. The binding of EE with HSA and BSA resulted in increase in emission characteristics of HSA and BSA and a significant blue spectra shift. In contrast, the interaction of NOR with HSA and BSA quenched the emission characteristics of HSA and BSA. The observed emission spectral shifts preclude the effective use of traditional univariate regression analysis of fluorescent data for the determination of EE and NOR concentrations in HSA and BSA samples. Multivariate partial-least-squares (PLS) regression analysis was utilized to correlate the changes in emission spectra with EE and NOR concentrations in HSA and BSA samples. The figures-of-merit of the developed PLS regression models were excellent, with limits of detection as low as 1.6*10(-8) M for EE and 2.4*10(-7) M for NOR and good linearity (R(2)>0.994985). The PLS models correctly predicted EE and NOR concentrations in independent validation HSA and BSA samples with a root-mean-square-percent-relative-error (RMS%RE) of less than 6.0% at physiological condition. On the contrary, the use of univariate regression resulted in poor predictions of EE and NOR in HSA and BSA samples, with RMS%RE larger than 40% at physiological conditions. High accuracy, low sensitivity, simplicity, low-cost with no prior analyte extraction or separation required makes this method promising, compelling, and attractive alternative for the rapid determination of estrogen concentrations in biomedical and biological specimens, pharmaceuticals, or environmental samples. PMID- 26992538 TI - Rice husk as an adsorbent: A new analytical approach to determine aflatoxins in milk. AB - Aflatoxins determinations are usually expensive and employ environmentally unfriendly procedures, thus, the search for new materials and technologies, that are both ecologically safe, inexpensive and able to fulfill its role with little pre-processing is growing. One interesting approach is employing by-products as adsorbents during the extraction step of aflatoxins especially in products such as milk and dairy that are so important in basic dietary. Thus, a method to use rice husk, an agroindustry residue that is a promising material to adsorb aflatoxins to enable further analysis steps, is proposed by applying a Plackett Burman design followed by 2(2) central composite rotational design. Rice husks were prepared by washing the husk with a solvents sequence. The washed particles were analysed by scanning electron microscopy, characterized by an elemental analyser and analysed for the presence of pesticides and mycotoxins. The rice husks contained 41% carbon, 4.3% hydrogen and 0.2% nitrogen, without mycotoxins and pesticides. The adsorptions were conducted using 0.5 g of rice husk, with 42 mesh, and 10 mL of milk contaminated with several know levels of aflatoxins M1 and B1. The solution was filtrated trough the adsorbent layer using a pressure of 10 in. Hg. The adsorbed mycotoxins were removed with 6 mL of methanol:chloroform (80:20). This condition achieved recovery of around 100% for both mycotoxins, with the average quantity of mycotoxin adsorbed equal 0.0150 ug g(-1) of afla B1 and 0.0174 ug g(-1) of afla M1. PMID- 26992539 TI - Recognition of Mg2+ by a new fluorescent "turn-on" chemosensor based on pyridyl hydrazono-coumarin. AB - A new fluoroionophore PyHC bearing 2-pyridylhydrazone and 7-hydroxycoumarin moieties for selective detection of Mg(2+) was synthesized and characterized. This chemosensor exhibited "turn-on" fluorescence behavior and was sensitive to Mg(2+) concentrations as low as 105 nmol L(-1) in ethanol-water solution. Detailed spectroscopic studies revealed the binding mode of a 1:1 complex between PyHC and Mg(2+) that leads to a fluorescence enhancement. PMID- 26992540 TI - 1,8-naphthalimide modified [12]aneN3 compounds as selective and sensitive probes for Cu2+ ions and ATP in aqueous solution and living cells. AB - A new fluorescent probe 1 featuring one 1,8-naphthalimide and two [12]aneN3 units was synthesized. In the presence of Cu(2+) ions, the fluorescence emission of 1 was quenched by a factor of 127-fold and no interference by other metal ions was observed under physiological conditions. By means of titration and a Job's plot it was established that 1 forms a complex with Cu(2+) ions in a 1:2 ratio. The fluorescence of the 1-Cu(2+) complex was recovered by the addition of Adenosine 5'-triphosphate (ATP) in aqueous solution. Due to its low cytotoxicity, good water solubility, and high sensitivity, probe 1 was successfully applied in the sequential recognition of Cu(2+) and ATP in aqueous solution and HeLa cells. The highly selective and sensitive ability of 1-Cu(2+) complex to detect ATP even enables its bio-analytical applications in real-time imaging in living cells. PMID- 26992541 TI - Analysis of zwitterionic, cationic, and anionic poly- and perfluoroalkyl surfactants in sediments by liquid chromatography polarity-switching electrospray ionization coupled to high resolution mass spectrometry. AB - A new analytical method is proposed for the determination of a wide span of fluoroalkylated surfactants (PFASs) of various chain lengths and polarities in sediments, including newly-identified compounds such as zwitterionic and cationic PFASs. Extraction conditions were optimized so as to maintain a common preparation procedure for all analytes (recovery range: 60-110%). Instrumental analysis was performed with ultra-high performance liquid chromatography coupled to Orbitrap mass spectrometry through polarity-switching electrospray ionization. Calibration curves with excellent coefficients of determination (R(2)>0.994) were generally obtained over 0.002-10ngg(-1) dry weight (dw) and limits of detection were in the range 0.0006-0.46 ng g(-1) dw. Intra-day precision remained<9% and inter-day precision<23%. While perfluorooctane sulfonate (PFOS) generally prevailed over other perfluoroalkyl acids (PFAAs) in sediments from mainland France, fluorotelomer sulfonamide amines and fluorotelomer sulfonamide betaines were also ubiquitous in these samples, especially in the vicinity of airports wherein firefighting training activities may occur on a regular basis. PMID- 26992542 TI - Cobalt internal standard for Ni to assist the simultaneous determination of Mo and Ni in plant materials by high-resolution continuum source graphite furnace atomic absorption spectrometry employing direct solid sample analysis. AB - A new method is proposed for the simultaneous determination of Mo and Ni in plant materials by high-resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GFAAS), employing direct solid sample analysis (DSS) and internal standardization (IS). Cobalt was used as internal standard to minimize matrix effects during Ni determinations, enabling the use of aqueous standards for calibration. Correlation coefficients for the calibration curves were typically better than 0.9937. The performance of the method was checked by analysis of six plant certified reference materials, and the results for Mo and Ni were in agreement with the certified values (95% confidence level, t-test). Analysis was made of different types of plant materials used as renewable sources of energy, including sugarcane leaves, banana tree fiber, soybean straw, coffee pods, orange bagasse, peanut hulls, and sugarcane bagasse. The concentrations found for Mo and Ni ranged from 0.08 to 0.63 ng mg(-1) and from 0.41 to 6.92 ng mg(-1), respectively. Precision (RSD) varied from 2.1% to 11% for Mo and from 3.7% to 10% for Ni. Limits of quantification of 0.055 and 0.074 ng were obtained for Mo and Ni, respectively. PMID- 26992543 TI - Application of the angle measure technique as image texture analysis method for the identification of uranium ore concentrate samples: New perspective in nuclear forensics. AB - The identification of interdicted nuclear or radioactive materials requires the application of dedicated techniques. In this work, a new approach for characterizing powder of uranium ore concentrates (UOCs) is presented. It is based on image texture analysis and multivariate data modelling. 26 different UOCs samples were evaluated applying the Angle Measure Technique (AMT) algorithm to extract textural features on samples images acquired at 250* and 1000* magnification by Scanning Electron Microscope (SEM). At both magnifications, this method proved effective to classify the different types of UOC powder based on the surface characteristics that depend on particle size, homogeneity, and graininess and are related to the composition and processes used in the production facilities. Using the outcome data from the application of the AMT algorithm, the total explained variance was higher than 90% with Principal Component Analysis (PCA), while partial least square discriminant analysis (PLS DA) applied only on the 14 black colour UOCs powder samples, allowed their classification only on the basis of their surface texture features (sensitivity>0.6; specificity>0.6). This preliminary study shows that this method was able to distinguish samples with similar composition, but obtained from different facilities. The mean angle spectral data obtained by the image texture analysis using the AMT algorithm can be considered as a specific fingerprint or signature of UOCs and could be used for nuclear forensic investigation. PMID- 26992544 TI - Sensitivity enhancement in the fluorometric determination of aliphatic amines using naphthalene-2,3-dicarboxaldehyde derivatization followed by vortex-assisted liquid-liquid microextraction. AB - A highly sensitive liquid chromatographic method was developed for the fluorometric determination of trace amounts of linear aliphatic primary amines. Prior to extraction, amines were derivatized with naphthalene-2,3 dicarboxaldehyde (NDA) in the presence of cyanide ion (CN) and extracted by vortex-assisted liquid-liquid microextraction (VALLME). The optimum conditions were as follows: derivatization reaction time for 5 min in 2.0 mL aqueous donor samples with 50 MUM NDA/CN, and 10mM borate buffer at pH 9; vortex extraction time for 20s in the VALLME step with 50 MUL of isooctane as the extractant phase; centrifugation for 1 min at 6000 rpm. Under the optimum conditions, the limits of detection (LOD) were between 0.01 and 0.04 nmol L(-1). The calibration curves showed good linearity in the range of 0.1-20 nmol L(-1). In comparison with previous work using o-phthalaldehyde/2-mercaptoethanol derivatization, the method has much more stable fluorescent derivatives, higher fluorescence intensities, and greater extraction efficiencies. The sensitivity enhancement factors (SEF) were between 2 and 70, which is in good agreement with the theoretical values calculated from partition coefficients in VALLME system. PMID- 26992545 TI - Ionic liquids as a key medium for efficient extraction of copper complexes from chia seeds (Salvia hispanica L.). AB - Due to insufficient information, the aim of study was to concern on the optimization of extraction procedure of selected metal complexes with flavonoids from chia seeds. Evaluation of the amount of elements in compound, not only their total concentration content, is highly important due to the fact, that only a part from total content of metal is absorbed by human body. At the beginning the total amount of elements in chia seeds was established as 14.51+/-0.42 ug g(-1) for copper, 57.44+/-1.23 ug g(-1) for manganese, 81.12+/-1.89 ug g(-1) for zinc and 0.35+/-0.13 ug g(-1) for cobalt. After the most suitable solvent was established, effects of several parameters on the efficiency of metal extraction were studied. Solvent concentration, solid-solvent ratio, extraction method, extraction time and temperature have been investigated as independent variables. The optimal extraction conditions included vortexing during 20 min in 50 degrees C, using an ionic liquid (1-butyl-3-methylimidazolium bromide) as an extractant, with solid-solvent ratio of 1:20. The determination of total and extractable amount of metals in chia seeds was carried out by standalone ICP MS. In addition, a complementary analysis of extracted metal complexes was performed using SEC-ICP MS method. It was confirmed that the ionic liquid is able to extract different copper complexes in comparison with commonly used solvents. The study indicated that extraction by using an ionic liquid has been successfully applied for determination of metals and metal complexes in chia seeds. PMID- 26992546 TI - Accurate quantification of total chromium and its speciation form Cr(VI) in water by ICP-DRC-IDMS and HPLC/ICP-DRC-IDMS. AB - Two analytical procedures have been developed for the determination of total chromium (TCr) and its highly toxic species, i.e. Cr(VI) in water samples using the following methods: inductively coupled plasma dynamic reaction cell isotope dilution mass spectrometry (ICP-DRC-IDMS) and high performance liquid chromatography inductively coupled plasma dynamic reaction cell isotope dilution mass spectrometry (HPLC/ICP-DRC-IDMS). Spectral interferences, predominantly occurring in chromium determination, were removed using a dynamic reaction cell (DRC). The presented procedures facilitate the quantification of trace amounts - below 1 ug L(-1) of TCr and individual Cr species - in various water matrices including drinking water and still bottled water with different mineral composition. Special attention has been paid to the adequate preparation of isotopically enriched (53)Cr(VI) standard solution in order to avoid artifacts in chromium speciation. Both procedures were fully validated as well as establishing the traceability and estimation of the uncertainty of measurement were carried out. Application of all of the above mentioned elements and of the isotope dilution technique, which provides the highest quality of metrological traceability, allowed to obtain reliable and high quality results of chromium determination in water samples. Additionally, the comparison of two methods: HPLC/ICP-DRC-MS and HPLC/ICP-DRC-IDMS for Cr(VI) determination, was submitted basing on the validation parameters. As a result, the lower values for these parameters were obtained using the second method. PMID- 26992547 TI - Electric field-assisted solid phase extraction and cleanup of ionic compounds in complex food matrices: Fluoroquinolones in eggs. AB - The use of electric fields as additional driving forces in sample preparation techniques is an innovative approach that is environmentally friendly, straightforward, and able to overcome several limitations of conventional sample preparation procedures. In this work, the advantages of electric field-assisted solid phase extraction (E-SPE) using syringe-type cartridges were demonstrated for the extraction of four fluoroquinolones (FQs) in their anionic forms. The FQs were extracted from eggs and subsequently determined by UHPLC-MS/MS. The use of electric fields during the washing and final elution steps resulted in a significant improvement of the extraction efficiencies for almost all FQs when compared to conventional SPE. Intra- and inter-day assays showed coefficients of variation below 10%. The better cleanup also resulted in the appearance of less precipitated matter in the final eluate, as well as reduced matrix effects. The results showed that the electrophoretic forces derived from electric fields are a promising way of significantly increasing the extraction efficiency of ionic analytes, while minimizing matrix effects associated with complex samples. PMID- 26992548 TI - Facile synthesis of 5 nm NaYF4:Yb/Er nanoparticles for targeted upconversion imaging of cancer cells. AB - 5nm intense green emission NaYF4:Yb/Er upconversion nanoparticles (UCNPs) with pure beta phase was synthesized with a simple "green" strategy for the first time. Traditional organic solvothermal method is often applied to prepare the high-quality and uniform UCNPs, but the preparation of lanthanide-oleate complexes is laborious as heating and multistep post-treatment for purification are often required. The water-alcohols solvothermal method is environmentally friendly, but the fabricated UCNPs have big size, poor biocompatibility and high cytotoxicity, which limited their application for cell imaging. Herein, NaYF4:Yb/Er UCNPs were prepared with rare-earth nitrates RE(NO3)3 (RE=Y0.80 Yb0.18 Er0.02) as precursors and diethylene glycol (DEG)/ethylene glycol (EG)/water as the solvent. A facile green solvothermal method with the temperature being controlled at 300 degrees C was developed. The as-prepared NaYF4:Yb/Er UCNPs were characterized and were found to have enhanced UC emission and controllable particle size. The as-prepared UCNPs were further functionalized via folic acid coating for the targeted imaging and improved bio- compatibility. It was made the UCNPs potential for upconversion bioimaging of living cells by the strong upconversion luminescence, the excellent biocompatibility, and the super-small size. The good colloidal stability and low cell cytotoxicity of the as-prepared UCNPs and the developed synthesis protocol might advance both the fields of UCNPs and biomolecule-based nanotechnology for future studies. PMID- 26992549 TI - Method for the fast determination of bromate, nitrate and nitrite by ultra performance liquid chromatography-mass spectrometry and their monitoring in Saudi Arabian drinking water with chemometric data treatment. AB - A rapid, sensitive and precise method for the determination of bromate (BrO3(-)), nitrate (NO3(-)) and nitrite (NO2(-)) in drinking water was developed with Ultra performance Liquid Chromatography-Mass Spectrometry (UPLC-ESI/MS). The elution of BrO3(-), NO3(-) and NO2(-) was attained in less than two minutes in a reverse phase column. Quality parameters of the method were established; run-to-run and day-to-day precisions were <3% when analysing standards at 10 ug L(-1). The limit of detection was 0.04 ug NO2(-) L(-1) and 0.03 ug L(-1) for both NO3(-)and BrO3( ). The developed UPLC-ESI/MS method was used to quantify these anions in metropolitan water from Saudi Arabia (Jeddah, Dammam and Riyadh areas) and commercial bottled water (from well or unknown source) after mere filtration steps. The quantified levels of NO3(-) were not found to pose a risk. In contrast, BrO3(-) was found above the maximum contaminant level established by the US Environmental Protection Agency in 25% and 33% of the bottled and metropolitan waters, respectively. NO2(-) was found at higher concentrations than the aforementioned limits in 70% and 92% of the bottled and metropolitan water samples, respectively. Therefore, remediation measures or improvements in the disinfection treatments are required. The concentrations of BrO3(-), NO3(-) and NO2(-) were mapped with Principal Component analysis (PCA), which differentiated metropolitan water from bottled water through the concentrations of BrO3(-) and NO3(-) mainly. Furthermore, it was possible to discriminate between well water; blend of well water and desalinated water; and desalinated water. The point or source (region) was found to not be distinctive. PMID- 26992550 TI - Development of the sensitive lateral flow immunoassay with silver enhancement for the detection of Ralstonia solanacearum in potato tubers. AB - Ralstonia solanacearum is a dangerous and economically important pathogen of potatoes and other agricultural crops. Therefore, rapid and sensitive methods for its routine diagnostics are necessary. The aim of this study was to develop a rapid control method for R. solanacearum with a low limit of detection (LOD) based on a lateral flow immunoassay (LFIA) with silver enhancement. To minimize the LOD, the membrane type, antibody amount for conjugation with gold nanoparticles, conjugate concentration and antibody concentration in the analytical zone were optimized. Silver enhancement was used to decrease the LOD of the LFIA. For silver enhancement, release fiberglass membranes with pre absorbed silver lactate and hydroquinone were placed on the analytical zone, and a drop of silver lactate was added. The LFIA with silver enhancement was found to be 10-fold more sensitive (LOD 2*10(2) CFU/mL; 20 min) in comparison with the common analysis (LOD 2*10(3) CFU/mL; 10 min). The specificity of the developed LFIA was studied using different strains of R. solanacearum (54 samples) and other widespread bacterial pathogens (18 samples). The LFIA detected all tested strains, whereas non-specific reactions were not observed. The developed tests were used for the control of bacteria in extracts of infected and non-infected potato tubers, and the quantitative analysis results (based on the densitometry of line colouration) were confirmed by ELISA with a correlation coefficient equal to 0.965. PMID- 26992551 TI - Evaluation of water-use efficiency in foxtail millet (Setaria italica) using visible-near infrared and thermal spectral sensing techniques. AB - Water limitations decrease stomatal conductance (g(s)) and, in turn, photosynthetic rate (A(net)), resulting in decreased crop productivity. The current techniques for evaluating these physiological responses are limited to leaf-level measures acquired by measuring leaf-level gas exchange. In this regard, proximal sensing techniques can be a useful tool in studying plant biology as they can be used to acquire plant-level measures in a high-throughput manner. However, to confidently utilize the proximal sensing technique for high throughput physiological monitoring, it is important to assess the relationship between plant physiological parameters and the sensor data. Therefore, in this study, the application of rapid sensing techniques based on thermal imaging and visual-near infrared spectroscopy for assessing water-use efficiency (WUE) in foxtail millet (Setaria italica (L.) P. Beauv) was evaluated. The visible-near infrared spectral reflectance (350-2500 nm) and thermal (7.5-14 um) data were collected at regular intervals from well-watered and drought-stressed plants in combination with other leaf physiological parameters (transpiration rate-E, A(net), g(s), leaf carbon isotopic signature-delta(13)C(leaf), WUE). Partial least squares regression (PLSR) analysis was used to predict leaf physiological measures based on the spectral data. The PLSR modeling on the hyperspectral data yielded accurate and precise estimates of leaf E, gs, delta(13)C(leaf), and WUE with coefficient of determination in a range of 0.85-0.91. Additionally, significant differences in average leaf temperatures (~1 degrees C) measured with a thermal camera were observed between well-watered plants and drought-stressed plants. In summary, the visible-near infrared reflectance data, and thermal images can be used as a potential rapid technique for evaluating plant physiological responses such as WUE. PMID- 26992553 TI - Prevalence and Risk Factors for Voice Problems Among Soccer Coaches. AB - OBJECTIVES: The prevalence of voice problems has been investigated in various occupations, but research investigating sports coaches' voice problems seems to be limited even if coaches are an occupational group whose work requires heavy voice use. The aim of this study was to determine the prevalence of voice problems among soccer coaches and identify risk factors that can contribute to the problems. METHODS/DESIGN: The data were collected with a web questionnaire that was sent to 500 soccer coaches. Overall, 109 male coaches, who practiced soccer coaching to various extents, responded to the questionnaire. The presence of six vocal symptoms was investigated, as well as environmental factors and health-related factors that may have an influence on the voice. RESULTS: The results showed that the prevalence of voice problems among soccer coaches was high. In total, 28.4% of the participants reported two or more frequently occurring vocal symptoms. The most common symptom was throat clearing or coughing followed by voice becomes low or hoarse. The coaches who had vocally demanding main occupations alongside their coaching tasks had an increased risk for voice problems. Moreover, a significant association was found between chronic rhinitis and frequently occurring vocal symptoms, as well as between stress and frequently occurring vocal symptoms. CONCLUSIONS: Given the extent of voice problems and the fact that soccer coaches have a vocally demanding occupation, it would be important to increase the awareness of voice use among this group. Soccer coaches are in immense need of more information about voice ergonomics during their coaching education. PMID- 26992552 TI - Thrombospondin-1 promotes mesenchymal stromal cell functions via TGFbeta and in cooperation with PDGF. AB - Mesenchymal stromal cells (MSC) are characterized by unique tropism for wounded tissues, high differentiating capacity, ability to induce tissue repair, and anti inflammatory and immunoregulatory activities. This has generated interest in their therapeutic use in severe human conditions as well as in regenerative medicine and tissue engineering. Identification of factors involved in the regulation of MSC proliferation, migration and differentiation could provide insights into the pathophysiological regulation of MSC and be exploited to optimize clinical grade expansion protocols for therapeutic use. Here we identify thrombospondin-1 (TSP-1) as a major regulator of MSC. TSP-1 induced MSC proliferation. This effect was mediated by TSP-1-induced activation of endogenous TGFbeta, as shown by the inhibitory effects of anti-TGFbeta antibodies and by the lack of activity of TSP-2 - that does not activate TGFbeta. Moreover, TSP-1 strongly potentiated the proliferative and migratory activity of PDGF on MSC. TSP 1 directly bound to PDGF, through a site located within the TSP-1 type III repeats, and protected the growth factor from degradation by MSC-derived proteases, hence increasing its stability and bioavailability. The studies presented here identify a more comprehensive picture of the pleiotropic effect of TSP-1 on MSC behavior, setting the basis for further studies aimed at investigating the possible use of PDGF and TSP-1 in the in vitro expansion of MSC for therapeutic applications. PMID- 26992554 TI - Investigation of Voice Pathology Detection and Classification on Different Frequency Regions Using Correlation Functions. AB - OBJECTIVES AND BACKGROUND: Automatic voice pathology detection and classification systems effectively contribute to the assessment of voice disorders, which helps clinicians to detect the existence of any voice pathologies and the type of pathology from which patients suffer in the early stages. This work concentrates on developing an accurate and robust feature extraction for detecting and classifying voice pathologies by investigating different frequency bands using correlation functions. In this paper, we extracted maximum peak values and their corresponding lag values from each frame of a voiced signal by using correlation functions as features to detect and classify pathological samples. These features are investigated in different frequency bands to see the contribution of each band on the detection and classification processes. MATERIAL AND METHODS: Various samples of sustained vowel /a/ of normal and pathological voices were extracted from three different databases: English, German, and Arabic. A support vector machine was used as a classifier. We also performed a t test to investigate the significant differences in mean of normal and pathological samples. RESULTS: The best achieved accuracies in both detection and classification were varied depending on the band, the correlation function, and the database. The most contributive bands in both detection and classification were between 1000 and 8000 Hz. In detection, the highest acquired accuracies when using cross correlation were 99.809%, 90.979%, and 91.168% in the Massachusetts Eye and Ear Infirmary, Saarbruecken Voice Database, and Arabic Voice Pathology Database databases, respectively. However, in classification, the highest acquired accuracies when using cross-correlation were 99.255%, 98.941%, and 95.188% in the three databases, respectively. PMID- 26992555 TI - Resonance Tuning in Three Girl Choristers. AB - OBJECTIVE: The phenomenon of resonance tuning, whereby a singer modifies the shape of their vocal tract to increase the acoustic power output, is commonly exploited across large pitch ranges by professional sopranos and has been observed to a lesser degree in nonexpert adult singers. This study considers the employment of two common resonance tuning techniques in experienced child singers; tuning the first vocal tract resonance to the fundamental (R1: fo) and tuning the second resonance to the second harmonic (R2:2 fo). METHODS: Wide-band excitation at the subject's mouth during singing was used to measure the vocal tract resonances of three girl choristers, and vowel formant values in speech were extracted from samples of spoken text. Measured resonance values were cross referenced with first and second harmonics for sung vowels across the subjects' ranges to identify the resonance tuning techniques employed, and these results were compared with those previously observed by others in professional adult classical singers. RESULTS AND CONCLUSIONS: There was clear evidence that the subjects employed resonance tuning techniques comparable with the strategies used by adult singers. The protocol and results presented here pave the way for further studies exploring the development of resonance tuning techniques in young soprano voices, with the potential to impact on approaches to classical singing training in the future. PMID- 26992556 TI - Voice Alterations in Patients With Spinocerebellar Ataxia Type 7 (SCA7): Clinical Genetic Correlations. AB - BACKGROUND/OBJECTIVES: Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by the expansion of a cytosine-adenine-guanine triplet located in the coding region of the ATXN7 gene, which is characterized by cerebellar ataxia, pigmentary macular degeneration, and dysarthria. Although dysarthria is a common feature in various SCA, its clinical characterization has been barely approached. PATIENTS/METHODS: In this study, we report, to our knowledge for the first time, a detailed voice analysis in a large series of patients with SCA7, using different vocal parameters, including jitter, shimmer, and fundamental frequency. Patients were molecularly diagnosed using fluorescent based polymerase chain reaction and capillary electrophoresis, and clinically characterized using the Scale for the Assessment and Rating of Ataxia and the Inventory of Non-Ataxia Symptoms. RESULTS: We found altered jitter, shimmer, and fundamental frequency measurements in patients with SCA7 compared with control subjects (P < 0.05). However, voice impairment was found unrelated with both age at disease onset and size of the cytosine-adenine-guanine triplet tract. Remarkably, jitter and shimmer measurements of patients were found to correlate with their Inventory of Non-Ataxia Symptoms, but not with their Scale for the Assessment and Rating of Ataxia scores, implying that voice impairment is the result of extra-cerebellar manifestations of the disease. CONCLUSIONS: We propose that deficiency of the extra-cerebellar component of SCA7 might lead to sudden changes in laryngeal muscle tone, producing instability in sustained vowel phonation. Clinical characterization of voice will help to discriminate SCA7 from other SCA and to guide vocal therapy treatments. PMID- 26992557 TI - The Accuracy of References in The Journal of Urology((r)). PMID- 26992558 TI - Editorial Comment. PMID- 26992559 TI - Editorial Comment. PMID- 26992560 TI - Turning Points in the Conception and Regulation of Physician-Assisted Dying in the Netherlands. PMID- 26992561 TI - A Multi-Modality Approach to Left Ventricular Aneurysms: True vs False. PMID- 26992562 TI - Differential activation of noncanonical SMAD2/SMAD3 signaling by bone morphogenetic proteins causes disproportionate induction of hyaluronan production in immortalized human granulosa cells. AB - Successful fertilization depends upon proper cumulus-oocyte complex (COC) expansion. Synthesized by hyaluronan synthases (HASs), hyaluronan forms the backbone of the COC matrix and plays a critical role in COC expansion. This study investigated the effects and mechanisms of ovarian BMPs on HAS expression and hyaluronan production in human granulosa cells. Treatment with BMP4, BMP6, BMP7 or BMP15 induced differing levels of noncanonical SMAD2/3, but equal levels of canonical SMAD1/5/8, phosphorylation which were mirrored by differing levels of HAS2 up-regulation and hyaluronan production. The effects of BMP4 and BMP15 on HAS2 mRNA were partially reversed by knockdown of SMAD3, and blocked by knockdown of SMAD2+SMAD3 or SMAD4. BMP4-induced SMAD2/3 phosphorylation and HAS2 mRNA up regulation were mediated by both BMP and activin/transforming growth factor-beta type I receptors. Our results suggest differential activation of noncanonical SMAD2/SMAD3 signaling by BMPs causes disproportionate induction of HAS2 expression and hyaluronan production in immortalized human granulosa cells. PMID- 26992563 TI - Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation. AB - Smooth muscle metaplasia (SMM) and fibrotic tissues are frequently seen in endometriotic lesions, yet the mechanisms underlying their formation are poorly understood. In this study, we investigated the roles of activated platelets in driving epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT) in endometriosis. Through in vitro experimentations, we found that activated platelets, through the release of TGF-beta1 and the induction of TGF-beta/Smad signaling pathway, promoted EMT and FMT in endometriosis, resulting in increased cell contractility, collagen production, and ultimately to fibrosis. TGF-beta blockade reversed these processes. Prolonged exposure of endometriotic stromal cells to activated platelets induced increased expression of alpha-SMA as well as markers of differentiated smooth muscle cells. Consequently, endometriotic lesions and their microenvironment contain all the necessary molecular machinery to promote SMM and fibrogenesis. Our results suggest that endometriotic lesions are wounds that undergo repeated injury and healing, highlighting the importance of platelets in the development of endometriosis. PMID- 26992565 TI - Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages. AB - Tissue-resident macrophages can derive from yolk sac macrophages (YS-Macs), fetal liver monocytes (FL-MOs), or adult bone-marrow monocytes (BM-MOs). The relative capacity of these precursors to colonize a niche, self-maintain, and perform tissue-specific functions is unknown. We simultaneously transferred traceable YS Macs, FL-MOs, and BM-MOs into the empty alveolar macrophage (AM) niche of neonatal Csf2rb(-/-) mice. All subsets produced AMs, but in competition preferential outgrowth of FL-MOs was observed, correlating with their superior granulocyte macrophage-colony stimulating factor (GM-CSF) reactivity and proliferation capacity. When transferred separately, however, all precursors efficiently colonized the alveolar niche and generated AMs that were transcriptionally almost identical, self-maintained, and durably prevented alveolar proteinosis. Mature liver, peritoneal, or colon macrophages could not efficiently colonize the empty AM niche, whereas mature AMs could. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages and the plasticity of the mononuclear phagocyte system is largest at the precursor stage. PMID- 26992564 TI - Oxysterol-related-binding-protein related Protein-2 (ORP2) regulates cortisol biosynthesis and cholesterol homeostasis. AB - Oxysterol binding protein-related protein 2 (ORP2) is a lipid binding protein that has been implicated in various cellular processes, including lipid sensing, cholesterol efflux, and endocytosis. We recently identified ORP2 as a member of a protein complex that regulates glucocorticoid biosynthesis. Herein, we examine the effect of silencing ORP2 on adrenocortical function and show that the ORP2 knockdown cells exhibit reduced amounts of multiple steroid metabolites, including progesterone, 11-deoxycortisol, and cortisol, but have increased concentrations of androgens, and estrogens. Moreover, silencing ORP2 suppresses the expression of most proteins required for cortisol production and reduces the expression of steroidogenic factor 1 (SF1). ORP2 silencing also increases cellular cholesterol, concomitant with decreased amounts of 22-hydroxycholesterol and 7-ketocholesterol, two molecules that have been shown to bind to ORP2. Further, we show that ORP2 binds to liver X receptor (LXR) and is required for nuclear LXR expression. LXR and ORP2 are recruited to the CYP11B1 promoter in response to cAMP signaling. Additionally, ORP2 is required for the expression of other LXR target genes, including ABCA1 and the LDL receptor (LDLR). In summary, we establish a novel role for ORP2 in regulating steroidogenic capacity and cholesterol homeostasis in the adrenal cortex. PMID- 26992566 TI - Evaluation of participants' perception and taste thresholds with a zirconia palatal plate. AB - PURPOSE: Zirconia and cobalt-chromium can withstand a similar degree of loading. Therefore, using a zirconia base for removable dentures could allow the thickness of the palatal area to be reduced similarly to metal base dentures. We hypothesized that zirconia palatal plate for removable dentures provides a high level of participants' perception without influencing taste thresholds. The purpose of this study was to evaluate the participants' perception and taste thresholds of zirconia palatal plate. METHODS: Palatal plates fabricated using acrylic resin, zirconia, and cobalt-chromium alloy were inserted into healthy individuals. Taste thresholds were investigated using the whole-mouth gustatory test, and participants' perception was evaluated using the 100-mm visual analog scale to assess the ease of pronunciation, ease of swallowing, sensation of temperature, metallic taste, sensation of foreign body, subjective sensory about weight, adhesiveness of chewing gum, and general satisfaction. RESULTS: For the taste thresholds, no significant differences were noted in sweet, salty, sour, bitter, or umami tastes among participants wearing no plate, or the resin, zirconia, and metal plates. Speech was easier and foreign body sensation was lower with the zirconia plate than with the resin plate. Evaluation of the adhesiveness of chewing gum showed that chewing gum does not readily adhere to the zirconia plate in comparison with the metal plate. The comprehensive participants' perception of the zirconia plate was evaluated as being superior to the resin plate. CONCLUSIONS: A zirconia palatal plate provides a high level of participants' perception without influencing taste thresholds. PMID- 26992567 TI - A novel model used to detect differential splice junctions as biomarkers in prostate cancer from RNA-Seq data. AB - BACKGROUND: In cancer alternative RNA splicing represents one mechanism for flexible gene regulation, whereby protein isoforms can be created to promote cell growth, division and survival. Detecting novel splice junctions in the cancer transcriptome may reveal pathways driving tumorigenic events. In this regard, RNA Seq, a high-throughput sequencing technology, has expanded the study of cancer transcriptomics in the areas of gene expression, chimeric events and alternative splicing in search of novel biomarkers for the disease. RESULTS: In this study, we propose a new two-dimensional peak finding method for detecting differential splice junctions in prostate cancer using RNA-Seq data. We have designed an integrative process that involves a new two-dimensional peak finding algorithm to combine junctions and then remove irrelevant introns across different samples within a population. We have also designed a scoring mechanism to select the most common junctions. CONCLUSIONS: Our computational analysis on three independent datasets collected from patients diagnosed with prostate cancer reveals a small subset of junctions that may potentially serve as biomarkers for prostate cancer. AVAILABILITY: The pipeline, along with their corresponding algorithms, are available upon request. PMID- 26992568 TI - Adapting machine learning techniques to censored time-to-event health record data: A general-purpose approach using inverse probability of censoring weighting. AB - Models for predicting the probability of experiencing various health outcomes or adverse events over a certain time frame (e.g., having a heart attack in the next 5years) based on individual patient characteristics are important tools for managing patient care. Electronic health data (EHD) are appealing sources of training data because they provide access to large amounts of rich individual level data from present-day patient populations. However, because EHD are derived by extracting information from administrative and clinical databases, some fraction of subjects will not be under observation for the entire time frame over which one wants to make predictions; this loss to follow-up is often due to disenrollment from the health system. For subjects without complete follow-up, whether or not they experienced the adverse event is unknown, and in statistical terms the event time is said to be right-censored. Most machine learning approaches to the problem have been relatively ad hoc; for example, common approaches for handling observations in which the event status is unknown include (1) discarding those observations, (2) treating them as non-events, (3) splitting those observations into two observations: one where the event occurs and one where the event does not. In this paper, we present a general-purpose approach to account for right-censored outcomes using inverse probability of censoring weighting (IPCW). We illustrate how IPCW can easily be incorporated into a number of existing machine learning algorithms used to mine big health care data including Bayesian networks, k-nearest neighbors, decision trees, and generalized additive models. We then show that our approach leads to better calibrated predictions than the three ad hoc approaches when applied to predicting the 5 year risk of experiencing a cardiovascular adverse event, using EHD from a large U.S. Midwestern healthcare system. PMID- 26992569 TI - High or low intensity text-messaging combined with group treatment equally promote weight loss maintenance in obese adults. AB - BACKGROUND: Text-message and e-mail are emerging as potential methods for improving weight outcomes among obese individuals. The optimal volume, frequency, and timing of such interventions are unknown. This study investigated the effect of adjunct technological support on weight and psychological variables after a 3 month cognitive-behaviour therapy (CBT) group intervention. METHODS: Sixty obese adults were randomised to a CBT programme plus intensive (text-message and e mail; CBT+ITS) or minimal (text-message only; CBT+MTS) technological support. Assessments occurred at baseline, 3-, 6-, 9-, and 15-months. Outcome variables included weight (kg), body mass index (kg/m2), waist circumference (cm), binge eating tendencies, weight self-efficacy, and weight control cognitions and behaviours. RESULTS: CBT+ITS (n=31) and CBT+MTS (n=29) participants lost 5.2% (+/ 1.1) and 4.7% (+/-1.1) of their baseline weight by 3-months, 8.4% (+/-1.2) and 6.4% (+/-1.1) by 6-months, 9.6% (+/-1.3) and 6.4% (+/-1.3) by 9-months, and sustained a 7.5% (+/-1.3) and 5.1% (+/-1.3) loss at 15-months, respectively. There were no significant differences between intensive and minimal support, however, the CBT+ITS group showed a marginal advantage across all anthropometric measures. CONCLUSIONS: A low intensity text-message support programme is just as effective as higher intensity technological support for maintaining weight loss in obese adults. This represents a low-cost means of aiding weight loss maintenance without reliance on extended face-to-face treatment. PMID- 26992570 TI - Temporal Patterns and Predictors of Rate vs Rhythm Control in Patients Attending a Multidisciplinary Atrial Fibrillation Clinic. AB - BACKGROUND: Contemporary trends in the selection of and persistence with rate vs rhythm control for atrial fibrillation (AF) are not well studied, particularly in the context of multidisciplinary AF clinics. METHODS: The initial arrhythmia management strategy in 1031 consecutive patients attending a multidisciplinary AF clinic from 2005-2012 was analyzed. RESULTS: The 397 (38.5%) patients initially treated with rhythm control were younger (57.4 +/- 14 years vs 65.6 +/- 13 years; P < 0.0001) and more likely to be men (64.5% vs 56.9%; P = 0.019). They also had fewer comorbidities, lower CHADS2 (Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) scores, and greater symptom burden. The proportion treated with rhythm control declined from 46.9% in 2005-2006 to 28.4% in 2012 (P for trend < 0.0001). Compared with those initially selecting rate control, patients treated with rhythm control required more frequent clinic encounters (7 [interquartile range {IQR}, 3-12] vs 3 [IQR, 2-7]; P < 0.001) and longer follow-up (266 days [IQR, 84-548 days] vs 99 days [IQR, 0-313 days]; P < 0.001). Younger age, absence of diabetes and sleep apnea, earlier treatment year, higher symptom burden, and rural residence were independently associated with rhythm control. Persistence with the initial treatment strategy was reduced in the rhythm-control group (P = 0.003). CONCLUSIONS: Use of rhythm control as the initial arrhythmia management strategy for AF in a specialty AF clinic is declining. Rhythm control requires more intensive follow-up and was more likely to lead to a change in arrhythmia management strategy. PMID- 26992572 TI - Identifying Frailty in Elderly Patients With Acute Coronary Syndrome. PMID- 26992571 TI - Novel Oral Anticoagulants and the Risk of Major Hemorrhage in Elderly Patients With Chronic Kidney Disease: A Nested Case-Control Study. AB - BACKGROUND: The novel oral anticoagulants, including dabigatran and rivaroxaban, differ in their degree of renal excretion. METHODS: We conducted a population based nested case-control study in patients 66 years and older with chronic kidney disease (CKD) (excluding patients undergoing chronic dialysis) who received an oral anticoagulant between April 2006 and March 2013. We calculated odds ratios for hospitalization with a major hemorrhagic event and receipt of dabigatran, rivaroxaban, or warfarin in the preceding 60 days. We also performed a sensitivity analysis to investigate whether a relationship exists between major hemorrhage and advanced age (age < 80 years or >= 80 years). RESULTS: We identified 237,409 patients with CKD, 4470 (1.9%) of whom experienced a major hemorrhage. We matched these patients to 14,460 controls. The use of dabigatran or rivaroxaban was not associated with a statistically significant elevated risk of hemorrhage compared with warfarin (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 0.91-1.45 for dabigatran; aOR, 1.22; 95% CI, 0.83-1.79 for rivaroxaban). Our sensitivity analysis found that older age was associated with an increased risk of hemorrhage for patients receiving dabigatran (aOR, 1.41; 95% CI, 1.06-1.88); results were similar but did not reach statistical significance for rivaroxaban (aOR, 1.57; 95% CI, 0.91-2.69). CONCLUSIONS: Among elderly patients with CKD, exposure to dabigatran or rivaroxaban was not associated with a statistically significant increased risk of major hemorrhagic events compared with exposure to warfarin. PMID- 26992573 TI - Competence of hosts and complex foraging behavior are two cornerstones in the dynamics of trophically transmitted parasites. AB - Multi-host trophically transmitted parasite (TTP) is a common life cycle where prey and predators are respectively intermediate and definitive hosts of the parasite. In these systems, the foraging response of the predator toward variations in prey community composition underlies the dynamic of the parasite. Therefore, modeling epidemiological dynamic of infectious diseases considering ecological predator-prey interactions is essential to understand the spreading of parasites in ecosystems. However, two important weaknesses of previous TTP models including feeding interaction can be pointed out: (i) the choice of a linear density-dependent contact rate is faintly realistic as it supposes an unlimited ingestion rate with an increase of prey density and (ii) considering only one host prey species prevents the study of host biodiversity effect due to change in the prey community composition where species have different competences to be infected and to transmit the parasite. This article attempts to address the dynamics of parasite in a context of multiple intermediate hosts differentiated by their competences and of complex foraging behavior of the predator. We present and analyze a deterministic one predator-two prey model, which is then used to explore the transmission cycle of the cestode Echinococcus multilocularis. This study examines the foraging condition for the co-existence of the prey, and then, based on the computation of the threshold measure of disease risk, R0, we show that the pattern of feeding interactions changes the relationship between disease risk and prey community composition. Finally, we disentangle the mechanism leading to the counter-intuitive observation of a decrease of disease risk while the population density of intermediate hosts increases. PMID- 26992574 TI - Disease and disaster: Optimal deployment of epidemic control facilities in a spatially heterogeneous population with changing behaviour. AB - Epidemics of water-borne infections often follow natural disasters and extreme weather events that disrupt water management processes. The impact of such epidemics may be reduced by deployment of transmission control facilities such as clinics or decontamination plants. Here we use a relatively simple mathematical model to examine how demographic and environmental heterogeneities, population behaviour, and behavioural change in response to the provision of facilities, combine to determine the optimal configurations of limited numbers of facilities to reduce epidemic size, and endemic prevalence. We show that, if the presence of control facilities does not affect behaviour, a good general rule for responsive deployment to minimise epidemic size is to place them in exactly the locations where they will directly benefit the most people. However, if infected people change their behaviour to seek out treatment then the deployment of facilities offering treatment can lead to complex effects that are difficult to foresee. So careful mathematical analysis is the only way to get a handle on the optimal deployment. Behavioural changes in response to control facilities can also lead to critical facility numbers at which there is a radical change in the optimal configuration. So sequential improvement of a control strategy by adding facilities to an existing optimal configuration does not always produce another optimal configuration. We also show that the pre-emptive deployment of control facilities has conflicting effects. The configurations that minimise endemic prevalence are very different to those that minimise epidemic size. So cost benefit analysis of strategies to manage endemic prevalence must factor in the frequency of extreme weather events and natural disasters. PMID- 26992575 TI - The Akt switch model: Is location sufficient? AB - Akt/PKB is a biochemical regulator that functions as an important cross-talk node between several signalling pathways in the mammalian cell. In particular, Akt is a key mediator of glucose transport in response to insulin. The phosphorylation (activation) of only a small percentage of the Akt pool of insulin-sensitive cells results in maximal translocation of glucose transporter 4 (GLUT4) to the plasma membrane (PM). This enables the diffusion of glucose into the cell. The dysregulation of Akt signalling is associated with the development of diabetes, cancer and cardiovascular disease. Akt is synthesised in the cytoplasm in the inactive state. Under the influence of insulin, it moves to the PM, where it is phosphorylated to form pAkt. Although phosphorylation occurs only at the PM, pAkt is found in many cellular locations, including the PM, the cytoplasm, and the nucleus. Indeed, the spatial distribution of pAkt within the cell appears to be an important determinant of downstream regulation. Here we present a simple, linear, four-compartment ordinary differential equation (ODE) model of Akt activation that tracks both the biochemical state and the physical location of Akt. This model embodies the main features of the activation of this important cross-talk node and is consistent with the experimental data. In particular, it allows different downstream signalling motifs without invoking separate feedback pathways. Moreover, the model is computationally tractable, readily analysed, and elucidates some of the apparent anomalies in insulin signalling via Akt. PMID- 26992576 TI - Steady states and stability in metabolic networks without regulation. AB - Metabolic networks are often extremely complex. Despite intensive efforts many details of these networks, e.g., exact kinetic rates and parameters of metabolic reactions, are not known, making it difficult to derive their properties. Considerable effort has been made to develop theory about properties of steady states in metabolic networks that are valid for any values of parameters. General results on uniqueness of steady states and their stability have been derived with specific assumptions on reaction kinetics, stoichiometry and network topology. For example, deep results have been obtained under the assumptions of mass-action reaction kinetics, continuous flow stirred tank reactors (CFSTR), concordant reaction networks and others. Nevertheless, a general theory about properties of steady states in metabolic networks is still missing. Here we make a step further in the quest for such a theory. Specifically, we study properties of steady states in metabolic networks with monotonic kinetics in relation to their stoichiometry (simple and general) and the number of metabolites participating in every reaction (single or many). Our approach is based on the investigation of properties of the Jacobian matrix. We show that stoichiometry, network topology, and the number of metabolites that participate in every reaction have a large influence on the number of steady states and their stability in metabolic networks. Specifically, metabolic networks with single-substrate-single-product reactions have disconnected steady states, whereas in metabolic networks with multiple-substrates-multiple-product reactions manifolds of steady states arise. Metabolic networks with simple stoichiometry have either a unique globally asymptotically stable steady state or asymptotically stable manifolds of steady states. In metabolic networks with general stoichiometry the steady states are not always stable and we provide conditions for their stability. In order to demonstrate the biological relevance we illustrate the results on the examples of the TCA cycle, the mevalonate pathway and the Calvin cycle. PMID- 26992578 TI - Multicenter assessment of the repeatability and reproducibility of the revised Venous Clinical Severity Score (rVCSS). AB - BACKGROUND: The Venous Clinical Severity Score (VCSS) was designed and validated as an objective measure of disease severity in patients with chronic venous disease (CVD). Recently, a revision of the VCSS (rVCSS) was performed to resolve ambiguity in the clinical descriptors and improve clarity and ease of use. This new revised VCSS requires validation to determine its repeatability and reproducibility in clinical evaluation of patients with varying levels of CVD. METHODS: A prospective multicenter protocol was designed to enroll patients undergoing evaluation for CVD at venous practices with experience using the original VCSS. At the time of initial evaluation, two clinicians independently assessed both lower extremities to determine the rVCSS and the CEAP clinical score. Between 1 and 6 weeks, patients returned and received repeat assessment of the rVCSS by the same two clinicians independently. Patients were excluded if any venous intervention occurred between the two separate evaluation visits. Scores were compared to determine inter- and intra-observer variability overall and within each CEAP clinical class. RESULTS: Seven centers enrolled a total of 136 limbs yielding 248 paired evaluations for interobserver variability and 258 paired evaluations for intraobserver variability. The mean interobserver rVCSS difference was 1.4 +/- 1.7 and the mean intraobserver variability was 1.3 +/- 1.6. Statistical assessment with weighted kappa yielded good repeatability (kappa = 0.68; P < .0001) and good reproducibility (kappa = 0.72; P < .000001) for the rVCSS. The rVCSS correlated well with the CEAP clinical class with significant differences between rVCSS in increasing classes. (P < .0001). CONCLUSIONS: In this multicenter evaluation, the rVCSS was demonstrated to be a reliable and reproducible instrument for documentation of the severity of symptoms in patients with lower extremity venous insufficiency. PMID- 26992577 TI - Turgidity-dependent petiole flexibility enables efficient water use by a tree subjected to water stress. AB - Water stress is a major cause of tree mortality. In response to drought, leaves wilt due to an increase in petiole flexibility. We present an analytical model coupling petiole mechanics, thermal balance, and xylem hydraulics to investigate the role of petiole flexibility in protecting a tree from water stress. Our model suggests that turgidity-dependent petiole flexibility can significantly attenuate the minimal xylem pressure and thus reduce the risk of cavitation. Moreover, we show that petiole flexibility increases water use efficiency by trees under water stress. PMID- 26992579 TI - Ultrasound-accelerated catheter-directed thrombolysis in acute iliofemoral deep venous thrombosis. AB - BACKGROUND: Iliofemoral deep venous thrombosis (DVT) is associated with a high incidence of the post-thrombotic syndrome. The current CHEST guidelines suggest that catheter-directed thrombolysis can be used for patients with acute iliofemoral DVT and severe leg complaints. Current literature shows that catheter directed thrombolysis increases patency of the affected tract and may reduce post thrombotic complications, but treatment time and bleeding complications are high. Ultrasound-accelerated catheter-directed thrombolysis (UACDT) uses ultrasound waves to enhance clot lysis, which should lower treatment time and bleeding complications with the same or higher patency rates. We report our clinical experience with UACDT on patency and complications in patients with acute iliofemoral DVT. METHODS: Patients treated with UACDT for acute iliofemoral DVT were included in our analyses. Diagnosis of iliofemoral DVT was confirmed using duplex sonography and magnetic resonance venography. In addition to thrombolysis, stents were placed or an arteriovenous fistula was created to ensure patency of the treated vein, if indicated. The main outcome is patency after 1 year. Secondary outcome measures are treatment time, bleeding complications, and pulmonary embolism. Patency was assessed using duplex sonography. RESULTS: In total, 37 patients (average age at intervention, 42 years; range, 5-76 years) were included. The DVT location was unilateral in 33 patients (20 left side, 13 right side), and four were bilateral. The average treatment time was 43 +/-17 hours. The success rate of thrombolysis was 95% (n = 35); re-thrombosis occurred in 11 (30%) patients. Major bleeding occurred in one patient (3%), and three minor bleedings occurred at the insertion side of the catheter (8%). One pulmonary embolism was encountered (3%). One patient had fever with positive blood cultures for Staphylococcus aureus. Additional procedures were required in 54% (n = 20) of patients. Primary patency was 70% at 1 year; secondary patency was 87% after 1-year follow up. CONCLUSIONS: UACDT of acute iliofemoral DVT is feasible and safe. Supplementary percutaneous transluminal angioplasty and stenting play an important role in preventing re-thrombosis. PMID- 26992580 TI - The incidence and characterization of deep vein thrombosis following ultrasound guided foam sclerotherapy in 1000 legs with superficial venous reflux. AB - OBJECTIVE: The incidence of deep vein thrombosis (DVT) following ultrasound guided foam sclerotherapy (UGFS) ranges from 0% to 5.7%. The aim of this study was to assess the incidence of DVT following UGFS in a single vascular center. METHODS: Patients undergoing UGFS between December 2005 and September 2011 underwent quality control duplex imaging within 2 weeks of treatment. This was performed by an independent senior vascular technologist, and data were entered on a prospectively maintained database. Deep venous segments assessed included common femoral vein, femoral vein, above- and below-knee popliteal veins, gastrocnemius, and tibial veins. DVT when present was labeled as endovenous foam induced thrombosis (EFIT) type 1 when thrombus was lining <25% of the lumen of the deep vein; type 2 when thrombus extension was 25% to 50%; type 3 when thrombus extension was 50% to 99%; and type 4 when the deep vein was occluded. RESULTS: A total of 1166 UGFS treatments were performed in 1000 legs (776 patients). Complete occlusion of the treated veins was seen in 84.5% of the legs after one session of treatment. Overall, 17 DVTs were detected (1.5%) with no DVTs detected in legs undergoing multiple treatments. Of the 17 episodes of DVT, 16 legs had DVT following treatment for truncal reflux (658 legs; 2.43%). Seven DVTs were EFIT type 1, two were type 2, two were type 3, and five were type 4. One DVT was seen in the gastrocnemius vein alone. Two of 1166 treatments (0.2%) resulted in a symptomatic DVT, both of which were EFIT type 4. On regression analysis, there was an increase in the risk of DVT when >=10 mL of foam was injected (odds ratio, 4.63; 95% confidence interval, 1.44-14.9; P = .01). CONCLUSIONS: The incidence of duplex-detected DVT following foam sclerotherapy is low and may be associated with the injection of >=10 mL of foam. PMID- 26992581 TI - The relationship between increased body mass index and primary venous disease severity and concomitant deep primary venous reflux. AB - BACKGROUND: The role of overweight in chronic venous disease is still controversial. The aim of this study was to evaluate the impact of overweight and obesity in chronic primary venous disease in relation to disease severity, using the CEAP and the Venous Clinical Severity Score (VCSS) as well as well as body weight on the presence of concomitant primary deep venous reflux. MATERIAL: Between October 2005 and September 2010, 1445 consecutive patients (2023 limbs) presenting with duplex ultrasound-confirmed chronic primary venous disease and planned for intervention were evaluated from a database. The patients were classified according to CEAP, the VCSS, and body mass index (BMI; kg/m(2)), using the World Health Organization definition. Concomitant primary deep venous reflux was evaluated and re-examined following eradication of the superficial reflux. RESULTS: There were 636 normal weight patients (890 limbs; BMI <25), 526 overweight patients (740 limbs; BMI 25 to 29.9), and 283 obese patients (393 limbs; BMI >=30 kg/m(2)). Overweight patients had more incompetent perforators (P < .001), hypertension (P < .001), and diabetes (P = .019) than normal weight patients and higher C class (CEAP classification) and VCSS (P < .001). Obese patients had more incompetent perforators (P < .001), hypertension (P < .001), diabetes (P = .004), and primary deep insufficiency (P < .001) than overweight patients as well as higher C class and VCSS (P < .001). Correlation between the C class and the VCSS was found excellent (r = 0.80). Obese patients had more axial reflux than the two other groups. There was no relationship between disease duration, body weight, and severity within each group. After eradication of superficial reflux, abolition of the deep reflux was lowest among obese patients (13.7%) compared with overweight patients (22.5%). CONCLUSIONS: There was a close relation between body weight and clinical severity of primary venous disease. Both overweight and obesity appear to be a separate risk factor for increased severity in patients with chronic primary venous disease without correlation to disease duration. CEAP and VCSS seem to accurately evaluate disease severity with an excellent correlation between the two scores. Concomitant primary deep venous reflux is more often observed in the obese patients, with less abolishment following eradication of the superficial reflux than observed for normal weight and overweight patients. PMID- 26992582 TI - Clinical and anatomic outcomes of endovenous radiofrequency ablation performed on symptomatic small-diameter great saphenous veins. AB - OBJECTIVE: The efficacy of radiofrequency ablation (RFA) for symptomatic varicose veins is well established. Alternatively, there is less consensus and little data on outcomes when treating great saphenous veins (GSV) of small diameter (<=5 mm). The purpose of this study is to assess clinical and anatomical outcomes of RFA on symptomatic patients with small GSV. METHODS: A retrospective analysis was performed on our symptomatic patients who received RFA of incompetent GSV without any concomitant adjunctive procedures between January 2008 and December 2011. Limbs with GSV thigh diameter <=5 mm and >5 mm on duplex while standing were subject to review. Clinical success was defined as an improvement in Venous Clinical Severity Score (VCSS) at 3 months. Anatomic success was defined as absence of venous flow <=3 cm distal to the saphenofemoral junction on duplex ultrasound examination. Changes in CEAP class were noted. RESULTS: In 307 patients, 55 limbs in 44 patients met inclusion criteria. Baseline median VCSS was 4 (interquartile range [IQR], 4, 5) for those patients with diameter <=5 mm. Clinical success was seen in 83% of limbs at 3 months with a median VCSS change of -2 (IQR, -3, -1). None of the treated limbs had phlebectomy for symptomatic refluxing GSV varicosities prior to 3-month follow up. One phlebectomy was performed for cosmesis at 78 days postprocedure. Anatomic success was achieved in 96% of limbs at 3 months. Baseline median CEAP was 2 (IQR, 2, 2). The median CEAP change at 3 months was 0 (IQR, -1, 0). One patient experienced thrombus extension into the saphenofemoral junction at 4 days. CONCLUSIONS: In our experience, RFA of symptomatic small-diameter GSV provides comparable clinical and anatomic outcomes to that of current published data. Our findings suggest that these patients benefit clinically from RFA. PMID- 26992583 TI - The impact of orthostatic challenge on arteriovenous hemodynamics and volume changes of the lower extremity. AB - OBJECTIVE: To assess the impact of an orthostatic challenge on arterial and venous hemodynamics and its relation to lower leg volume. METHODS: Hemodynamic parameters of 18 healthy subjects (six men; mean age, 38 +/- 11 years) were assessed in the left proximal superficial femoral artery and femoral vein in supine position and during a 10-minute orthostatic challenge using duplex sonography. Lower leg volume was measured using an optoelectronic device. RESULTS: During orthostatic challenge, vein diameter increased significantly while artery diameter decreased compared with the supine position (P < .01 for both). Arterial and venous blood flow in the supine (baseline) position was similar (P = .54). During the first 2 minutes of orthostatic challenge, both arterial and venous blood flow significantly decreased, with a more important decrease in venous blood flow (P < .01 compared with artery). Following this nadir, venous blood flow increased above baseline levels, followed by a plateau flow similar to baseline. Arterial flow returned to flow level inferior to baseline values (P < .05). Lower leg volume increased from 2348 +/- 399 mL to 2423 +/- 433 (P < .001) within the first 5 minutes with no further increase thereafter. CONCLUSIONS: A 10-minute orthostatic challenge has a marked impact on both arterial and venous hemodynamics with a multiphasic change of venous and arterial flow. Lower leg volume increase correlates with venous and arterial flow response. These findings help to better understand the role of gravitational force in various vascular diseases of the lower extremities. PMID- 26992584 TI - Increasing ablation distance peripheral to the saphenofemoral junction may result in a diminished rate of endothermal heat-induced thrombosis. AB - OBJECTIVE: The treatment of venous insufficiency using endovenous laser ablation or radiofrequency ablation may result in endothermal heat-induced thrombosis (EHIT), a form of deep venous thrombosis. This study sought to assess whether increasing the ablation distance peripheral to the deep venous junction would result in a reduction in the incidence of EHIT II. METHODS: This study was a retrospective review of a prospectively maintained database from April 2007 to December 2011. Consecutive patients undergoing great saphenous vein (GSV) or small saphenous vein (SSV) ablation were evaluated. Previous to February 2011, all venous ablations were performed 2 cm peripheral to the saphenofemoral or saphenopopliteal junction (group I). Subsequent to February 2011, ablations were performed greater than or equal to 2.5 cm peripheral to the respective deep system junction (group II). The primary outcome was the development of EHIT II or greater (ie, thrombus protruding into the deep venous system but comprising less than 50% of the deep vein lumen). Secondary outcomes included procedure-site complications such as thrombophlebitis and hematomas. chi(2) tests were performed for all discrete variables, and unpaired Student's t-tests were performed for all continuous variables. P < .05 was considered statistically significant. RESULTS: A total of 4223 procedures were performed among group I (n = 3239) and group II (n = 984). Patient demographics were similar between the two groups; however, the CEAP classification was higher by a small margin in group II, and the result was significant (group I: 2.6% +/- 0.9% vs group II: 2.8% +/- 1.0%; P = .006). The incidence of EHIT II was 76 in group I and 13 in group II. This represented a trend toward diminished frequency in group II as compared with group I (group I: 2.3% vs group II: 1.3%; P = .066). There were no reported cases of EHIT III or IV in this patient cohort. Patients who developed an EHIT II in group I were treated using anticoagulation 54% of the time, and patients who developed an EHIT II in group II were treated using anticoagulation 100% of the time. CONCLUSIONS: This study suggests that changing the treatment distance from 2 cm to greater than or equal to 2.5 cm peripheral to the deep venous junction may result in a diminished incidence of EHIT II. Ongoing evaluation is required to validate these results and to affirm the long-term durability of this technique. PMID- 26992585 TI - Experience at 1 year with the moving tip technique of radiofrequency ablation for the treatment of symptomatic venous malformations in the head and neck. AB - PURPOSE: To evaluate the effectiveness and safety of performing radiofrequency ablation (RFA) using the moving tip technique to treat venous malformations (VMs) in the head and neck. METHODS: Ten patients (male:female ratio, 2:8; median age, 38 years; age range, 27-59 years) prospectively underwent RFA using the moving tip technique as the first treatment. Improvement of their clinical symptoms, volume reduction of the treated VMs as determined by ultrasound (US) or magnetic resonance imaging (MRI), and any patient complications were evaluated at 1, 3, 6, and 12 months after RFA. RESULTS: All patients underwent follow-up examinations 12 months after RFA. The following criteria were used to evaluate these patients: (1) symptomatic VMs were diagnosed by US, MRI, and the patients' clinical history; (2) superficially located VMs were evaluated using a linear 12-MHz US probe to determine the tumor volume; and (3) localized and limited VMs were evaluated using the Hamburg classification. The mean symptom score of the 10-cm visual analog scale and the mean volume reduction of the VMs as measured by MRI at the 6-month follow-up examination were significantly decreased from 8.0 (range, 7.0-9.0) to 2.0 (range, 1.0-3.0) and from 18.8 (range, 8.3-28.2) cm(3) to 8.5 (range, 4.2-14.1) cm(3), respectively (P < .05). No major patient complications were noted. CONCLUSIONS: RFA using the moving tip technique is an effective and safe method for treating localized VMs in the head and neck. PMID- 26992586 TI - Outcomes of endovascular intervention for May-Thurner syndrome. AB - BACKGROUND: Endovascular interventions for May-Thurner syndrome (MTS) have become first-line therapy, often performed in a young patient population despite the lack of robust supportive data. This article reports on long-term outcomes from a large series of patients treated in the setting of de novo or postthrombotic presentation. METHODS: A retrospective review of MTS patients treated between 2006 and 2010 was conducted at two institutions. Patients who presented with acute iliofemoral deep vein thrombosis (DVT) were treated with either catheter directed thrombolysis (CDT) and/or pharmacomechanical thrombolysis and identified as having a venous stenosis by venogram or intravascular ultrasound (IVUS). Patients who presented with chronic venous insufficiency symptoms or recalcitrant ulceration but no DVT and evidence of MTS on duplex ultrasound, magnetic resonance venography, or computerized tomography venography were evaluated by venography. IVUS was selectively utilized. Stenting of the iliocaval junction was performed in all patients with a >50% diameter stenosis by IVUS or venogram. RESULTS: Seventy patients with MTS underwent 77 lower extremity interventions. They were divided into two groups: postthrombotic (group 1) and de novo presentation of chronic swelling/pain or ulceration but no DVT (group 2). There were 56 extremities in group 1 and 21 extremities in group 2. Both groups were comparable in terms of gender distribution and comorbidities, but hypercoagulable state was more common in group 1 (P = .014), and average CEAP and Villalta scores on presentation were higher in group 2 (P < .001). There were left-sided symptoms in 40 (78%) patients in group 1 and 15 (79%) in group 2 (P = 1.00). Female patients were more likely to have left-sided symptoms compared with male patients (odds ratio, 4.88; 95% confidence interval, 1.49-15.89; P = .014). The average stent size was significantly different among the groups (P < .027), with different types used in each group. There was one patient in group 1 who had significant periprocedural bleeding (1 unit transfused) during the CDT portion of the procedure. Mean follow up was 29.7 months in group 1 (range, 18.4-58.3 months) and 22.4 months in group 2 (range, 17.1-42 months). Complete or partial symptom relief was reported for 52 (92.9%) extremities in group 1 and 20 (95.2%) extremities in group 2 (P = 1.00). The overall primary patency of group 1 at 36 months by life-table analysis was 91% with a secondary patency of 95%. The primary and secondary patency for group 2 was 91% at 36 months. CONCLUSIONS: Stenting of MTS has proven to be safe, efficacious, and durable for up to 36 months in both the postthrombotic patient as well as those treated for edema alone. PMID- 26992587 TI - Superior hemodynamic performance of a thigh-length versus knee-length intermittent pneumatic compression device. AB - OBJECTIVE: There is a lack of consensus regarding which length of intermittent pneumatic compression (IPC) device provides optimal thromboprophylaxis. This trial was conducted to compare hemodynamic performance of a thigh-length and knee length IPC device. The hypothesis is that thigh-length IPC will be more efficient in preventing stasis. METHODS: This single-center trial tested the thigh-length sleeve (TLS) and knee-length sleeve (KLS) in 47 healthy volunteers. Peak systolic velocity and total volume flow were measured at rest and during the 11-second compression cycle. Measurements were obtained at the popliteal vein for the KLS and at the common femoral vein for the TLS. RESULTS: The study was completed by 47 volunteers (32 women, 15 men), who were a mean age of 39.7 years (range, 18-68 years). There was a statistically significant difference in augmented total volume flow and peak systolic velocity between the KLS and TLS favoring the TLS: median total volume flow was 357.54 mL/min for the KLS vs 668.21 mL/min for the TLS (P < .0001), and median peak systolic velocity was 47.70 cm/s for the KLS vs 58.47 cm/s for the TLS (P = .0019). CONCLUSIONS: This trial suggests that the improved hemodynamic effects of a thigh-length IPC system may provide superior thromboprophylaxis to a knee-length IPC. PMID- 26992588 TI - Development of functionally patent lymphatic meshes in postsurgical long-term resolution of peripheral secondary lymphedema. AB - OBJECTIVE: In oncologic surgery, secondary lymphedema of male external genital organs and upper or lower limbs frequently develops as a result of excision or mechanical obstruction of collecting lymphatic trunks. We evaluated whether the short-term and long-term outcomes of microsurgical treatment of limb and genital organs improves tissue drainage in patients with secondary lymphedema by restoring the pre-existing lymphatic networks or through new lymphangiogenesis. METHODS: Of 110 secondary lymphedema patients, microsurgery was performed in 45 hospitalized patients. Patients were aged 25 to 75 years, had at least third degree lymphedema, no satisfactory results from previous physical or pharmacologic therapy, without primitive neoplasia, at least 1 year since the last postsurgical adjuvant oncological treatment, and <15 years since the previous primary oncologic lymphedema development. A microsurgical lymphovenous shunt of the spermatic cord (n = 7), a lymphovenous shunt of the lower limbs (n = 32), or lymphatic grafting of the upper limbs (n = 6) was performed. The male external genitals were treated through an innovative lymphovenous shunt of the lymphatic collectors in the pampiniform plexus of the spermatic cord. For lower limb lymphedema, the lymphatics were shunted to the collaterals or saphenous vein. For upper limb lymphedema, a shunt was performed between the lymph vessels of the jugular-supraclavicular area and those in close continuity with the axillary region. The patency of the new lymphatic pathways was assessed using Photodynamic Eye (Hamamatsu Photonic K.K., Tokyo, Japan) lymphography. RESULTS: Six months postoperatively, 36 responding patients showed an almost complete recovery from secondary lymphedema. Lymphatic meshes, consisting of several lymphatic vessels merging into well-canalized and complex networks developing in the perianastomotic area or between the adjacent proximal anastomotic lymphatic collectors, were commonly observed in patients who positively responded to microsurgery. These complexes were never encountered in nonresponding patients or in normal, nonedematous tissue. CONCLUSIONS: Long-term postsurgical recovery from severe secondary lymphedema requires canalizing the lymphatic collectors along their original flow pattern and developing perianastomotic meshes. Because this phenomenon can be observed with the same characteristics in different tissues, such as the spermatic cord and the inguinocrural, inguinoscrotal, inguinotesticular, and brachial regions, the development of meshes seems to reflect a generalized phenomenon of local lymphangiogenesis triggered by the microsurgical procedure. PMID- 26992589 TI - Effective control of massive venous bleeding by "multioverlapping therapy" using polysaccharide nanosheets in a rabbit inferior vena cava injury model. AB - OBJECTIVE: To investigate the efficacy of multioverlapping therapy using a polysaccharide nanosheet having 75-nm thickness for sealing and stopping massive venous hemorrhage. METHODS: The hydrostatic durability of the polysaccharide nanosheet was evaluated in vitro when secured to an incised silicon tube. For in vivo studies, the inferior vena cava (IVC) of rabbits was cut longitudinally, and multiple polysaccharide nanosheets were overlapped onto the injured IVC. RESULTS: The mechanical hydrostatic durability of the nanosheets was gradually augmented by an increasing number of multilayered nanosheets in vitro. This durability was saturated at 80 +/- 6 mm Hg by four layers of nanosheets, which was robust enough to seal injured vessel walls of the large IVC. Multioverlapping therapy using nanosheets effectively sealed and stopped bleeding from the injured IVC in vivo. One month later, no inflammatory tissue response was observed around the nanosheet attachment sites of the IVC, while conventional suturing repair in control rabbits showed a severe inflammatory response around the sutured area. CONCLUSIONS: The multioverlapping therapy using the polysaccharide nanosheets will effectively stop massive venous bleeding without adverse effects in the immediate or chronic postoperative setting. PMID- 26992590 TI - Cyanoacrylate glue for the treatment of great saphenous vein incompetence in the anticoagulated patient. AB - The Sapheon Venaseal Closure System (Sapheon Inc, Santa Rosa, Calif), using cyanoacrylate glue, has provided a new modality of treatment, with patients treated without both tumescent anesthesia and postoperative compression. We present the first case of great saphenous vein occlusion performed using glue while the patient was fully anticoagulated with warfarin. This was tolerated well, and the treated vein showed complete early occlusion at 8 weeks; however at 6 months, extensive recanalization was demonstrated on duplex imaging. PMID- 26992591 TI - Endovascular exclusion of a large external iliac vein aneurysm. AB - Iliac vein aneurysms are uncommon, and there is no consensus on optimal treatment. We present a case of venous exclusion using an endovascular approach. To our knowledge, this is the first reported case of a large external iliac vein aneurysm treated endovascularly. We have demonstrated the feasibility of this approach with satisfactory 1-year follow-up. PMID- 26992592 TI - Open surgical removal of a tilted and dislodged inferior vena cava filter through a lumbar branch without cavotomy. AB - Retrievable inferior vena cava (IVC) filters decrease the risk of pulmonary embolism. Retrieval is recommended but device migration, tilting, or perforation of the IVC by the filter may prevent successful removal. We present a case of a tilted IVC filter with the retrieval hook lodged in a lumbar vein preventing endovascular removal. A subcostal incision was used for open removal. The thrombosed lumbar vein was encircled with vessel loops, facilitating collapse of the filter. No cavotomy was made. This technique, with minimal variation, can be used to remove most nonthrombosed retrievable filters from the IVC, without the need for venotomy. PMID- 26992593 TI - Imaging features and follow-up of large extrahepatic portal vein aneurysm. PMID- 26992594 TI - Endovascular management of inferior vena cava filter perforation. PMID- 26992595 TI - Inferior vena cava filters: Some evidence from the past and a look to the future. AB - Venous thromboembolism is a national health concern. Up to 58% of patients suffering from major multisystem trauma will experience venous thromboembolism if no measures are taken to prevent it. Of those, 10% to 30% will be fatal. The appropriate use of lower extremity compression, anticoagulation, and the use of inferior vena cava (IVC) filters has helped reduce the overall morbidity and mortality from this disease. The development of lower-profile devices and the ability to retrieve IVC filters has led to a liberalization of their use. The majority of the filters used today have achieved U.S. Food and Drug Administration approval through the 510K mechanism (approval based on prior similar devices rather than safety studies of the proposed device), and therefore, no rigorous investigations have been performed on them. Initially seeming safe, a recent increase in reports of filter migration, vena cava perforation, and vena cava thrombosis has prompted the Food and Drug Administration to ask for more information on their patterns of use, safety, efficacy, and retrievability. This report details some of the available data on the subject of IVC filters and the discussion surrounding the topic of prophylactic IVC filters in trauma patients. PMID- 26992596 TI - Forearm Isosulfan blue injection in the treatment of postoperative lymphatic complications. AB - Lymphatic leakage is an uncommon but serious complication following vascular procedures. When conservative measures fail, accurate identification and ligation of disrupted lymphatic channels is necessary to avoid recurrence. We report the case of a 52-year-old male with a left forearm lymphocele, which occurred following repair of an interosseous artery pseudoaneurysm. Successful lymphatic identification and ligation was performed using intradermal injection of Isosulphan blue dye at the time of operation. PMID- 26992597 TI - Polytetrafluoroethylene large vein replacements and high-altitude treks: Footnotes and footprints from Ben Eiseman's panoply of interests. PMID- 26992600 TI - Information for readers. PMID- 26992598 TI - Correction. PMID- 26992601 TI - Events of interest. PMID- 26992602 TI - Guidelines or gospels? AB - In the interest of advancing evidenced-based medicine, enthusiasm for clinical practice guidelines has skyrocketed. They have a genuine impact on clinical practice and are frequently referenced in the literature. Their construction is complex and labor intensive, and has significant limitations given the necessary process as well as the data available. There has been less focus on their appropriate clinical application as dictated by these inherent limitations. It is worthwhile taking a step back and considering how we know what we think we know based on statistical analysis of biomedical data sets and the real implications of those population data for making predictions about the individual patient we encounter in the clinic. These data as used to establish guidelines for care should be the foundation and starting point for our thoughtful recommendations and decision making, not the final word. The importance of nuance in clinical judgment remains even in this "evidence-based" world. PMID- 26992603 TI - Midterm benefits of surgical pulmonary embolectomy for acute pulmonary embolus on right ventricular function. AB - OBJECTIVE: Surgical pulmonary embolectomy has been used for the successful treatment of massive and submassive pulmonary emboli. The purpose of this study is to document the short- and midterm echocardiographic follow-up of right ventricular function after surgical pulmonary embolectomy for acute pulmonary embolus. METHODS: A retrospective review of the local Society of Thoracic Surgeons database of patients who underwent surgical pulmonary embolectomy for acute pulmonary embolectomy was conducted from 1998 to 2014 at a US academic center. Patients with chronic thrombus were excluded. The institutional echocardiographic database was searched for follow-up studies to compare markers of right ventricular function. Unadjusted outcomes were described, and quantitative comparisons were made of short- and long-term echocardiographic data. RESULTS: A total of 44 patients were included for analysis; 35 patients (79.5%) had a submassive pulmonary embolectomy, and 9 patients (20.5%) had a massive pulmonary embolectomy and required preoperative inotropy. Mean cardiopulmonary bypass time was 68.0 +/- 40.2 minutes, and 30 patients (68.2%) underwent procedures without aortic crossclamping. There was 1 in-hospital mortality (2.3%), and there were no permanent neurologic deficits. A total of 21 patients had echocardiography results available for follow-up. Perioperative echocardiographic data showed an immediate decrease in tricuspid regurgitant velocity and right ventricular pressure (P < .05). Mean midterm echocardiographic follow-up was 30 months in 12 patients. At midterm follow-up, improvements in right ventricular function observed postoperatively persisted. Only 1 patient had moderate right ventricular dysfunction, and no patient had worse than mild tricuspid regurgitation. Mean tricuspid valve regurgitant velocity was 2.4 +/- 0.7 m/s, and mean pulmonary artery systolic pressure was 37.2 +/- 14.2 mm Hg. CONCLUSIONS: Surgical pulmonary embolectomy may represent optimal therapy in selected patients for massive and submassive acute pulmonary emboli given the low morbidity and mortality rates. Echocardiographic follow-up shows preserved improvement in right ventricular function in the majority of patients. PMID- 26992604 TI - Fire in the "hall"! Myocardial inflammation and recurrence of atrial fibrillation. PMID- 26992606 TI - Discussion. PMID- 26992605 TI - Does RIFLE score a bullseye with AKI and post-redo CABG outcomes? PMID- 26992607 TI - Effect of high mannose glycan pairing on IgG antibody clearance. AB - IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). These Fc glycans influence effector functions and can alter clearance rates. Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. Since both forms can exist on therapeutic antibodies and the ratio can differ between products, measuring their relative levels is necessary to properly estimate effects on clearance. PMID- 26992608 TI - Photovoice: A Strategy to Better Understand the Reproductive and Sexual Health Needs of Young Mothers. AB - STUDY OBJECTIVE: Adolescent women face significant sexual and reproductive health challenges and are more vulnerable than their male peers. Photovoice methodology might allow them to provide more meaningful and accurate representations of the health challenges they encounter. Our objectives were to: (1) use Photovoice to understand how young mothers frame reproductive and sexual health within the context of their lives; (2) explore how they define reproductive and sexual health; (3) identify youth perspectives on how their life situations influence their ability to affect their health; and (4) connect their perspectives to social determinants of health framework to facilitate implementation of effective programs and policies to address their needs. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a prospective qualitative community-based participatory research study involving young women (ages 15-25 years) recruited from a local youth outreach center. A 9-step validated qualitative participatory approach that combined documentary photography with focus groups was used. Qualitative analysis was conducted with NVivo version 10 software (QSR International Inc., Burlington, MA, USA). Data were coded and themes were developed. RESULTS: Thirty women were recruited and nine women completed the study. Key themes included: personal sexual health practices and coping skills, influence of poverty, physical environments, community resources and sexual health services, education, and stigma of pregnancy. Participating in community-based participatory research empowered participants to advocate for their own health. CONCLUSION: Photovoice methodology contributes to understanding complex factors influencing sexual and reproductive health of young mothers. This participatory-based methodology highlights their individual situations, allowing us to seek connections, create analytical perspectives from which to relate their situations to root causes, and consider strategies for change. PMID- 26992609 TI - Association between inflammation biomarkers, anatomic extent of deep venous thrombosis, and venous symptoms after deep venous thrombosis. AB - OBJECTIVE: Inflammation may play a role in pathogenesis of venous thromboembolism, but the nature of this relationship is not yet understood. The objective of this study was to assess whether inflammation marker levels measured at diagnosis of deep venous thrombosis (DVT) and change in levels during the first month after DVT are associated with anatomic extent of DVT and severity of venous signs and symptoms at baseline and 1 month. METHODS: The BioSOX study is a biomarker substudy of the Compression Stockings to Prevent the Post-Thrombotic Syndrome (SOX) trial, a multicenter, randomized controlled trial that included patients with a first, acute, symptomatic, proximal DVT. Blood samples were collected from participants at baseline and 1 month, and C-reactive protein (CRP), intercellular adhesion molecule 1, interleukin (IL)-6, and IL-10 were measured by established assays. Linear regression was used to assess the association between continuous log-transformed baseline biomarker levels and anatomic extent of DVT, classified as iliac or common femoral DVT vs femoral or popliteal DVT (reference). Proportional odds ordinal logistic regression models were used to analyze the association between biomarker level and Villalta score (as a measure of severity of venous signs and symptoms) at baseline and 1 month. RESULTS: Among 717 patients, 60.2% were male, and the mean age was 55.2 years. There was a significant association between more extensive DVT (common femoral or iliac) and levels of CRP and IL-6 at DVT diagnosis. Median (interquartile range) CRP level was 11.6 mg/L (3.84-39.5) in patients with common femoral or iliac DVT vs 6.86 mg/L (3.11-22) in patients with popliteal or femoral DVT, and median IL-6 level was 6.36 pg/mL (1.09-14.37) vs 4.40 pg/mL (2.35-8.27), respectively. These differences were statistically significant in linear regression analyses. In addition, compared with those in the lowest quartile, each higher quartile of baseline CRP concentration was associated with an odds ratio of 2.89 (1.93-4.33) for having a more severe Villalta category at baseline and 1.98 (1.28-3.08) for having a more severe Villalta category 1 month after DVT. Higher baseline levels of IL-6 were associated with Villalta severity category at baseline (odds ratio, 2.40 [1.61-3.59]). Change in biomarker levels during the first month after DVT was not strongly associated with the 1-month Villalta score. CONCLUSIONS: Levels of CRP and IL-6 at DVT diagnosis were associated with thrombotic disease burden, as measured by DVT extent, and severity of DVT symptoms and signs. Further studies are required to more fully elucidate the role of inflammation in DVT and its clinical course. PMID- 26992611 TI - Morphologic changes in the vein after different numbers of radiofrequency ablation cycles. AB - OBJECTIVE: It has not yet been clarified whether it is possible to decrease the percentage of recurrences after radiofrequency (RF) ablation by way of increasing the number of RF ablation cycles. The aim of this study was to assess the morphologic changes in excised vein fragments after different durations of RF ablation exposure. METHODS: In the first part of the study, we performed a morphologic analysis of eight cases of great saphenous vein (GSV) recanalization 6 months after RF ablation. The second part was performed on a suprafascial segment of the GSV with a length of >22 cm and a minimum diameter of 5 mm in 10 patients, who had given their consent to intraoperative excision of suprafascial GSV segments after RF ablation treatment through four 1-cm-long diametrical cuts. Prior ultrasound analysis had shown an average 6.9-mm diameter of the suprafascial segments. The segment was divided into three 7-cm-long subsegments and one control segment. The first, second, and third segments were treated with three, two, and one RF ablation cycles (ClosureFast; Covidien, Mansfield, Mass), respectively; the control segment was not exposed to RF ablation at all. Morphologic study of 160 sections of the vein (five sections of each segment and 10 control specimens) was carried out. The specimens were dyed with hematoxylin and orcein. The ensuing analysis was performed by an experienced expert with the blind study method (the specimens were numbered without any hint as to the quantity of RF ablation cycles performed on them). The intergroup comparison of the depth of venous wall damage was based on comparison of the coefficient of alteration, which is calculated as the relation of damage depth to thickness of the vein. RESULTS: After one RF ablation cycle, the depth of blurring of the structural elements only on some portions reached the middle of the muscle layer of the wall (coefficient of alteration, alpha = 26%). After two cycles, blurring of the structural elements on some portions extended to the adventitia (alpha = 53%). After three cycles, uniform blurring of the structural elements of all layers of the venous wall up to the adventitia was seen (alpha = 92%). The statistically significant difference in the alteration coefficient, depending on the number of cycles of RF ablation (P < .005), was established. CONCLUSIONS: The number of RF ablation cycles has an impact on the depth of vein wall damage. One and two cycles do not cause damage to all layers of the vein wall. Three cycles cause damage to all vein wall layers. PMID- 26992610 TI - Role of coexisting contralateral primary venous disease in development of post thrombotic syndrome following catheter-based treatment of iliofemoral deep venous thrombosis. AB - BACKGROUND: It has been reported that early clot removal benefits patients with iliofemoral deep venous thrombosis (DVT) by removing obstruction and preserving valve function. However, a substantial number of patients who had successful clot removal develop post-thrombotic syndrome (PTS). Residual thrombus and rethrombosis play a part in this phenomenon, but the role of coexisting primary chronic venous disease (PCVD) in these patients has not been studied. METHODS: All patients who underwent catheter-based techniques of thrombus removal for symptomatic acute iliofemoral DVT during a 5-year period compose the study group. These patients were assessed for PTS by the Villalta scale, the Venous Clinical Severity Score (VCSS), and the Venous Insufficiency Epidemiological and Economic Study on Quality of Life (VEINES-QOL) questionnaire. The presence of coexisting PCVD was determined by clinical and duplex ultrasound findings in the contralateral leg at the time of the initial DVT diagnosis. Patients who had coexisting PCVD were compared with those without PCVD. RESULTS: Forty patients (40 limbs) were included in the study group. At initial diagnosis, 15 patients (38%) had coexisting symptomatic primary valve reflux in the unaffected limb. After thrombolysis, 9 of 40 limbs (22%) had complete lysis, 29 (73%) had >= 50% to 99% lysis, and 2 (5%) had <50% lysis. The mean percentage of lysis in patients with or without PCVD was similar (78% vs 86%; P = .13). Patients without coexisting PCVD had significantly better Villalta score and VCSS compared with those with coexisting PCVD (Villalta score, 2.52 vs 3.27, P = .014; VCSS, 2.96 vs 3.29, P = .005). Forty-five percent of patients (18 of 40) developed PTS. Patients who developed PTS had less clot lysis than those without PTS. This was true for patients with coexisting PCVD (60% vs 85%; P = .025) and in patients without PCVD (75% vs 89%; P = .013). There was no significant difference in the VEINES-QOL score between those with or without PCVD (79.5 vs 80.5; P = .9). Patients who had reflux in the treated limb after lysis had a five times greater chance for development of PTS compared with those who retained normal valve function during follow-up (odds ratio, 5.3; 95% confidence interval, 1.6-17.045). However, in patients with normal veins in the contralateral leg, the chance of development of PTS was 1.5 times higher if reflux was present in the treated limb (odds ratio, 1.49; 95% confidence interval, 0.043-10.253). CONCLUSIONS: Coexisting PCVD is a contributing factor to development of PTS after treatment of iliofemoral DVT with thrombus removal techniques. PMID- 26992612 TI - Retrievable inferior vena cava filters can always be removed using "fall-back" techniques. AB - OBJECTIVE: Retrievable inferior vena cava filters (IVCFs) left in place for a prolonged period can lead to complications including filter migration, fracture, and caval thrombosis. "Fall-back" techniques for IVCF retrieval that can be used when standard snaring is unsuccessful have been recently described. The purpose of this study was to analyze how incorporation of these new techniques affected the outcomes of IVCF retrievals at our institution during the past 5 years. METHODS: Data were collected of all patients undergoing IVCF removal by vascular surgeons at a tertiary academic medical center between 2009 and 2013, including demographics and procedural and filter characteristics. A standard technique of snaring the retrieval hook was attempted first in all cases; if this was unsuccessful, a number of fall-back techniques were employed, including the use of endoscopic graspers, 18F sheaths, and snaring a second wire below the collar of the filter to collapse it into the sheath. RESULTS: IVCF retrieval was attempted in 275 patients; 3 were excluded intraoperatively because of thrombus in the filter. Most filters (97%) were Gunther Tulips (Cook Medical, Bloomington, Ind); 70% had been placed prophylactically before bariatric surgery. A total of 268 filters (98.5%) were retrieved successfully, 213 (79%) by standard snaring and 55 (21%) with fall-back techniques. In patients undergoing fall-back techniques, technical success was achieved 100% of the time. The median time since insertion was significantly longer in the fall-back group (173 days vs 83 days; P < .0001). Four intraoperative complications occurred; fractured wires embolized to the right atrium or pulmonary artery and were successfully removed endovascularly. The majority of the procedures (80%) were performed under sedation in both groups. CONCLUSIONS: Incorporation of fall-back techniques may allow 100% technically successful and safe removal of retrievable IVCFs and is especially useful in removing filters with prolonged dwell time. PMID- 26992614 TI - Complications with office-based venoplasties and stenting and their clinical correlation. AB - BACKGROUND: Endovenous therapy by venoplasty and stenting is rapidly gaining momentum and popularity in treatment of chronic venous insufficiency (nonthrombotic iliac vein lesions, in particular). The purpose of this study was to examine the results of office-based venoplasty and stenting procedures that were performed at our office-based facility from July 28, 2012, until April 28, 2013. The study focused on any complications during and after the procedure. METHODS: From July 2012 to April 2013, 245 patients underwent venography for the correction of suspected iliac vein stenosis in the office setting. Data included 74 patients undergoing bilateral iliac procedures and 137 patients undergoing unilateral procedures. The remaining 34 patients underwent venography only, without any intervention. The remaining 285 limbs were classified according to the Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification as follows: C1, n = 0; C2, n = 84; C3, n = 97; C4, n = 34; C5, n = 53, and C6, n = 17. Postprocedure pain was assessed with a Likert scale of 0 to 10, and scores were collected in 108 patients in the latter portion of the study once this was established to be our primary complication. Pain was considered to be significant if >= 5 (n = 20) and insignificant if <5 (n = 88). Pearson correlation was used to evaluate any correlation between pain and gender, age, laterality, CEAP scores (2-6), stent size, and balloon size. Fourteen patients had a history of prior deep venous thrombosis (DVT). RESULTS: Out of the series, 90 women and 47 men underwent unilateral intervention, and 23 women and 14 men underwent bilateral intervention. The average age was 69 years (range, 22-96; standard deviation [SD], +/- 13). In 20 patients with significant pain, the average pain score was 6 (range, 5-10; SD, +/- 1.4). In 88 patients with insignificant pain, the average pain score was 1.15 (range, 0-4; SD, +/- 1.5). The overall average pain score for 108 cases was 2 (range, 0-10; SD, +/- 2.4). Five patients (2%) who underwent intervention developed thrombosis of the iliac stent either <30 days (n = 4) or >30 days (n = 1); all five patients had history of DVT. No statistically significant correlation of pain to age, gender, laterality, CEAP scores (2-6), or stent and balloon size was found. No correlation was found between stent thrombosis and gender, age, laterality, CEAP scores (2-6), or stent and balloon size. No complications were reported, such as pseudoaneurysm formation, infection, and insertion site DVT, within 5 days. Iliac fossa hematoma developed 30 days after the procedure in one patient, who required hospital admission for evaluation and treatment. CONCLUSIONS: The correction of iliac vein outflow obstruction in office-based settings results in a low incidence of complications, such as thrombosis (2%), and average pain score of 2 of 10 on the Likert scale. The procedure is minimally invasive with minimal complications. PMID- 26992613 TI - Intrapartum temporary inferior vena cava filters are rarely indicated in pregnant women with deep venous thromboses. AB - OBJECTIVE: We previously demonstrated the usefulness of temporary inferior vena cava filters (t-IVCFs) to prevent pulmonary thromboembolism in pregnant women with deep venous thrombosis (DVT). However, there is currently no consensus on the indications for intrapartum t-IVCF in pregnant women with DVT. In this study, we re-evaluated the safety and usefulness of t-IVCF inserted in this condition. METHODS: A retrospective evaluation in a single center was performed of 45 Japanese patients (54 pregnancies) with DVT between 1989 and 2014. Intrapartum t IVCF insertion was indicated in patients who had or might have had extensive DVT located in iliofemoral veins and who had floating thrombi in the veins of their lower limbs. RESULTS: Eighteen patients (40%) had thrombophilias. Onset of DVT and delivery occurred at 17 +/- 9 weeks and 37 +/- 2 weeks of gestation, respectively. Twenty pregnant women underwent placement of an intrapartum t-IVCF. All t-IVCFs were successfully placed in the suprarenal inferior vena cava before delivery. Filter-related complications occurred in two cases (10%). One was an allergic reaction to the lidocaine used at the insertion, and another was dislocation of the t-IVCF to the right atrium. The t-IVCFs were placed for more acute DVT compared with the 34 pregnancies without t-IVCF; the onset of DVT with t-IVCF was significantly later (22 vs 12 weeks; P = .002), and the duration of unfractionated heparin therapy was significantly shorter (16 vs 28 weeks; P < .001). There was no case of clinical pulmonary embolism in the perinatal period. Thrombus was detected macroscopically at the removed t-IVCF in 15 cases; however, almost all were minute pieces. In only one case with protein S deficiency and placental abruption was a large thrombus captured in the t-IVCF, which was considered to have prevented a clinically relevant pulmonary embolus. CONCLUSIONS: Placement of a t-IVCF appears to be safe for pregnant women. However, intrapartum t-IVCF insertion is considered to be unnecessary for pregnant women with DVT who have received anticoagulation therapy at early onset of gestation and long term before delivery. Patients with thrombophilia and at high risk of hemorrhage may represent a subgroup of women who would benefit from t-IVCF placement, but larger prospective multicenter evaluations are required to establish that fact. PMID- 26992616 TI - Treatment of nutcracker syndrome with open and endovascular interventions. AB - OBJECTIVE: Nutcracker syndrome (NS) is a rare cause of hematuria, flank pain, and renal venous hypertension due to compression of the left renal vein (LRV) between the aorta and the superior mesenteric artery. To evaluate outcomes of open surgery and endovascular interventions, we reviewed our experience. METHODS: A retrospective review of clinical data of all patients treated at our institution with an intervention for NS between January 1, 1994, and February 28, 2014, was performed. Primary outcomes were morbidity and mortality. Secondary outcomes included late complications, patency, freedom from reintervention, and resolution of symptoms. RESULTS: Thirty-seven patients (30 female, seven male) with a mean age of 27 years (range, 14-62 years) were treated. The most frequent symptom was flank pain (97%); the most frequent sign was hematuria (68%). NS was diagnosed with duplex ultrasound scanning with measurement of LRV diameters and flow velocities (87%), with computed tomography or magnetic resonance venography (94%), and with contrast venography with measurement of pressure gradients (93%). Initial treatment was open surgery in 36 patients, endovascular in 1. Distal transposition of the LRV into the inferior vena cava (IVC) was performed in 31 patients. Adjunctive procedures to optimize venous outflow included great saphenous vein cuff in six patients, great saphenous vein patch in four, and both cuff and patch in four. Three patients had patch alone; two had transposition of the left gonadal vein into the IVC. Two patients had anterior reimplantation of retroaortic LRV into the IVC. There were no major early complications, renal failure, or mortality. Three patients underwent early reinterventions within 30 days (stent, two; open revision, one). All LRVs and left gonadal veins were patent at discharge. Follow-up was 36.8 +/- 52.6 months (range, 1-216 months). Reinterventions after 30 days were performed in eight patients because of LRV stenosis (n = 7) or LRV occlusion (n = 1). One stent migrated into the IVC and required endovascular removal with repeated stenting. Six patients required stenting. Primary, primary assisted, and secondary patencies at 24 months were 74%, 97%, and 100%, respectively. Freedom from reintervention at 12 and 24 months was 76% and 68%, respectively. Resolution of symptoms occurred in 33 patients (87%). CONCLUSIONS: Open surgery, mostly LRV transposition, remains a safe and effective treatment of patients with NS. However, one of three patients after open repair required reintervention, most frequently LRV stenting. Open reconstruction should be tailored to the patient's anatomy, and placement of vein cuff or patch may reduce restenosis. Although renal vein stents improved patency, the safety and durability of currently available stents need to be established. PMID- 26992615 TI - Technical considerations, outcomes, and durability of inferior vena cava stenting. AB - OBJECTIVE: Inferior vena cava (IVC) thrombosis is an uncommon condition but can cause devastating complications to those affected. Historically, this has been treated with an open surgical approach (with high morbidity) and with angioplasty in more recent years. Herein we describe technical aspects of stenting of the IVC in patients with recalcitrant chronic occlusive disease and evaluate its outcomes. METHODS: We reviewed all the patients treated in an endovascular fashion for venous disease at our institution from 2005 to 2014 to identify and to include those with IVC stent placement in this study. Clinical characteristics, treatment details, and outcomes data were collected from medical records. Primary end points were technical success, symptom resolution, freedom from reintervention, and patency rate at follow-up. RESULTS: Twenty-eight patients (15 men) with a mean age of 48 +/- 2.7 years underwent IVC stent placement for 16 occlusions (4 congenital) and 12 high-grade stenoses. Hypercoagulable state was noted in 14 patients, 7 of whom had malignant disease. A previously placed IVC filter was present in 13 patients. Median time from onset of symptoms to presentation was 81 months (3-480 months). Lytic therapy with tissue plasminogen activator (Alteplase) was performed in 12 patients for a median of 2 days (range, 1-3 days). Self-expanding stents (Wallstent; Boston Scientific, Natick, Mass) were used most commonly in the IVC (n = 22) with or without adjunctive use of balloon-expandable stents (Palmaz stent; Cordis, New Brunswick, NJ). Technical success was 100%. At median follow-up of 10 months (range, 0-56 months), thrombotic complications requiring reintervention occurred in four patients at 1, 4, 8, and 37 months. One patient died at 2 weeks secondary to underlying malignant disease. Freedom from reintervention, patency rate, and symptom-free survival rate at 2 years were 84%, 90%, and 80%. CONCLUSIONS: Endovascular stenting for chronic occlusive disease of the IVC is safe and effective in the midterm follow-up, with minimal morbidity. Reintervention rate is low, with excellent functional outcomes. PMID- 26992617 TI - Infraclavicular first rib resection for the treatment of acute venous thoracic outlet syndrome. AB - OBJECTIVE: Venous thoracic outlet syndrome (VTOS) is most commonly treated by transaxillary, supraclavicular, or paraclavicular approaches, based on surgeon preference. However, we have adopted an infraclavicular approach to VTOS as the surgical pathology is in the anterior costoclavicular space. We hypothesize that this approach, combined with catheter-directed thrombolysis (CDT) with venoplasty as needed, provides safe and effective treatment of patients with an acute presentation of VTOS. METHODS: We retrospectively reviewed all consecutive patients that underwent infraclavicular thoracic outlet decompression for an acute presentation of VTOS from July 2005 to February 2014 by a single surgeon. Acute presentation was defined as less than 14 days between the onset of symptoms and CDT. Demographics, primary and secondary subclavian vein patency, perioperative outcomes, and reinterventions were recorded. RESULTS: There were 33 patients that underwent an infraclavicular approach for treatment of VTOS. Average age was 35 years, and 61% were male. All patients underwent CDT, subsequent infraclavicular first rib resection, and intraoperative venography. Intraoperative subclavian vein angioplasty was performed in 70%. Median postoperative length of stay was 2 days (range, 2-6 days), blood loss was 78 mL (range, 20-200 mL), and operative time was 120 minutes (range, 76-166 minutes). Median follow-up was 78 days (range, 2-483 days). Follow-up ultrasound showed all patients having a patent subclavian vein at last follow-up. Reinterventions included two cases for rethrombosis and one case of hemothorax. Primary patency was 91%, and secondary patency was 100%. There were no complications of brachial plexus or phrenic nerve injury. All patients at last follow-up were symptom-free, and subclavian veins were patent. CONCLUSIONS: An infraclavicular approach is a safe and effective treatment for acute VTOS. It provides excellent access to the costoclavicular space for first rib resection and subclavian venolysis while at the same time minimizing the risk of brachial plexus and phrenic nerve injury. PMID- 26992618 TI - A novel method of edema fluid drainage in obstructive lymphedema of limbs by implantation of hydrophobic silicone tubes. AB - OBJECTIVE: Lymphedema of limbs is caused by partial or total obstruction of lymphatic collectors as a consequence of skin and deep soft tissue inflammation, trauma of soft tissues and bones, lymphadenectomy, and irradiation in cancer therapy. According to the statistics of the World Health Organization, around 300 million people are affected by pathologic edema of limbs. Effective treatment of such large cohorts has been a challenge for centuries. However, none of the conservative and surgical methods applied so far proved to restore the shape and function of limbs to normal conditions. Actually, physiotherapy is the therapy of choice as a main modality or supplementary to surgical procedures divided into two groups: the bridging drainage and excisional techniques. The microsurgical operations can be performed if some parts of the peripheral collecting lymphatics remain patent and partially drain edematous regions. However, in advanced cases of lymphedema, all main lymphatics are obstructed and tissue fluid accumulates in the interstitial spaces, spontaneously forming "blind channels" or "lakes." The only solution would be to create artificial pathways for edema fluid flow away to the nonobstructed regions where absorption of fluid can take place. The aim of this study was to form artificial pathways for edema fluid flow by subcutaneous implantation of silicone tubes placed along the limb from the lower leg to the lumbar or hypogastric region. METHODS: In a group of 20 patients with obstructive lymphedema of the lower limbs that developed after lymphadenectomy and irradiation of the pelvis because of uterine cancer with unsuccessful conservative therapy, implantation was done, followed by external compression as intermittent pneumatic compression and elastic support of tissues. Postoperative circumference measurements, lymphoscintigraphy, and ultrasonography of tissues were carried out during 2 years of follow-up. RESULTS: There was a fast decrease of calf circumference since the day of implantation during weeks by a mean 3% with stabilization afterward. Patency of tubes and accumulation of fluid around them were seen on ultrasonography and lymphoscintigraphy in all cases. No tissue cellular reaction to silicone tubes was noted. CONCLUSIONS: The simplicity of the surgical procedure, decrease of limb edema, and lack of tissue reaction to the implant make the method worth applying in advanced stages of lymphedema with large volumes of accumulated tissue edema fluid. PMID- 26992619 TI - Pilot in vivo study of an absorbable polydioxanone vena cava filter. AB - OBJECTIVE: The objectives of this study were to evaluate tensile strength retention of polydioxanone as a function of time in a swine venous system and to assess the feasibility of an absorbable inferior vena cava (IVC) filter made from polydioxanone in a pilot swine study. METHODS: Twenty strands (60 cm each) of size 1 polydioxanone absorbable suture (Ethicon, Somerville, NJ) were placed in the central venous system of domestic swine. Strands were harvested at weekly intervals during 10 weeks for tensile strength testing. Results were compared with control samples obtained from an in vitro engineered circulation system containing sodium phosphate buffer solution. Three IVC filters braided from polydioxanone suture were also catheter deployed in three swine to assess absorbable IVC filter feasibility. RESULTS: Polydioxanone retained 82% tensile strength in vitro vs 79% in vivo at 35 days (P > .22), the desired prophylactic duration. For IVC filters made from polydioxanone, technical success of placement was achieved in all three filters deployed (100%). Autologous thrombus deployed inferior to the filter remained trapped in the filter until thrombus resorption, with no evidence of pulmonary emboli on follow-up computed tomography. There were no instances of caval penetration, filter-induced IVC thrombosis, filter migration, or tilt >15 degrees with imaging and clinical follow-up carried out to 32 weeks. CONCLUSIONS: Strength retention of polydioxanone suture placed in the venous system of swine is similar to earlier in vitro studies out to 10 weeks (P > .06 for all weeks) and is more than sufficient (8.20 +/- 0.37 kg mean load at break for size 1) to trap thrombus. Pilot animal study suggests that an absorbable polydioxanone IVC filter can be catheter deployed to capture and to hold iatrogenically administered autologous thrombus through resorption. PMID- 26992621 TI - Variability in leg compression provided by gradient commercial stockings. AB - BACKGROUND: Compression stockings are commonly prescribed by physicians for lower extremity edema and venous insufficiency. However, no data are available for clinicians to assess the relative quality of various brands, particularly low cost generics now available directly to consumers through the Internet. We examined the actual compression provided by gradient stockings from multiple manufacturers. METHODS: A total of 36 class 2 (20-30 mm Hg) men's medium-sized below-knee compression stockings from six different manufacturers (n = 6 of each brand) with approximately the same quality and materials were chosen to be studied. Identifying brand names were removed, and they were randomly and blindly tested by a technician in accordance with accepted industry standards. A calibrated constant rate of extension tensile instrument (Zwick Z010; Zwick Roell, Ulm, Germany) was used, and the tension generated by the stockings at the ankle and calf was measured using minimum, average, and maximum circumference sizes. All measurements were performed in duplicate. RESULTS: The compression pressures generated by the stockings were almost all within the stated range of 20 to 30 mm Hg at the ankle, but all except one were below 20 mm Hg at the calf. There were also significant differences between manufacturers at both the ankle and the calf (P < .0001). The expected pressure reduction between the two locations varied, but one stocking had only a minimal 2 mm Hg (8%) gradient, which was significantly less than all of the other tested brands and below the recommended 20% to 50% reduction. Cost analysis demonstrated that the discount brands were significantly lower in price but provided absolute compression and pressure gradients similar to those of the more expensive brands. CONCLUSIONS: There is significant variability among stockings, both in the absolute pressures and in the pressure gradients generated from the ankle to the calf, thought to be functionally important for venous flow. The cheaper stockings offered the same degree of compression and pressure gradient as the more expensive brands. These results suggest the need for manufacturing standards in the United States and a revision in labeling requirements to mandate more accurate and complete pressure disclosures. PMID- 26992620 TI - Successful tissue engineering of competent allogeneic venous valves. AB - OBJECTIVE: The purpose of this study was to evaluate whether tissue-engineered human allogeneic vein valves have a normal closure time (competency) and tolerate reflux pressure in vitro. METHODS: Fifteen human allogeneic femoral vein segments containing valves were harvested from cadavers. Valve closure time and resistance to reflux pressure (100 mm Hg) were assessed in an in vitro model to verify competency of the vein valves. The segments were tissue engineered using the technology of decellularization (DC) and recellularization (RC). The decellularized and recellularized vein segments were characterized biochemically, immunohistochemically, and biomechanically. RESULTS: Four of 15 veins with valves were found to be incompetent immediately after harvest. In total, 2 of 4 segments with incompetent valves and 10 of 11 segments with competent valves were further decellularized using detergents and DNAse. DC resulted in significant decrease in host DNA compared with controls. DC scaffolds, however, retained major extracellular matrix proteins and mechanical integrity. RC resulted in successful repopulation of the lumen and valves of the scaffold with endothelial and smooth muscle cells. Valve mechanical parameters were similar to the native tissue even after DC. Eight of 10 veins with competent valves remained competent even after DC and RC, whereas the two incompetent valves remained incompetent even after DC and RC. The valve closure time to reflux pressure of the tissue-engineered veins was <0.5 second. CONCLUSIONS: Tissue-engineered veins with valves provide a valid template for future preclinical studies and eventual clinical applications. This technique may enable replacement of diseased incompetent or damaged deep veins to treat axial reflux and thus reduce ambulatory venous hypertension. PMID- 26992622 TI - Symptomatic iliofemoral deep venous thrombosis treated with hybrid operative thrombectomy. AB - During the past 15 years, strategies that promote immediate and complete thrombus removal have gained popularity for the treatment of acute-onset iliofemoral deep venous thrombosis. In this case report, we describe a novel operative approach to venous thrombus removal known as hybrid operative thrombectomy. The technique employs a direct inguinal approach with concomitant retrograde advancement of a balloon catheter by femoral venotomy. Moreover, it provides effective thrombus removal through a single incision, with or without stent placement, and has the advantage of a completion venogram. PMID- 26992623 TI - Endovascular stent reconstruction of a chronic total occlusion of the inferior vena cava using bidirectional wire access and a balloon puncture by a re-entry device. AB - Venous angioplasty with stenting of iliac veins is an important treatment option for patients suffering from post-thrombotic syndrome due to chronic venous obstruction. Interventional treatment of a chronically occluded vena cava, however, is challenging and often associated with failure. We describe a case of a chronic total occlusion of the entire inferior vena cava that was successfully recanalized using bidirectional wire access and a balloon puncture by a re-entry catheter to establish patency of the inferior vena cava. PMID- 26992624 TI - Functioning inferior vena cava filter caught in the act. PMID- 26992625 TI - The additional benefit of graduated compression stockings to pharmacologic thromboprophylaxis in the prevention of venous thromboembolism in surgical inpatients. AB - OBJECTIVE: The evidence base supporting the use of graduated compression stockings (GCS) for venous thromboembolism (VTE) prevention has been challenged, and there appears to be a lack of evidence for the additional benefit of GCS to pharmacologic thromboprophylaxis. This study aimed to summarize and quality assess the existing evidence concerning whether GCS offer a significant benefit in addition to pharmacologic thromboprophylaxis in surgical inpatients. METHODS: A systematic review of published literature was performed. Inclusion criteria were (1) randomized controlled trials (RCTs), (2) surgical inpatients, (3) study arms examining prophylactic-dose pharmacologic thromboprophylaxis alone or in conjunction with GCS, and (4) outcome of VTE. RESULTS: In the review, 1025 articles were screened, of which 27 RCTs were included. Six RCT study arms included patients with GCS in conjunction with pharmacologic thromboprophylaxis, whereas 22 RCT study arms included patients treated with pharmacologic thromboprophylaxis alone. One RCT had both of its study arms included in the systematic review. The total number of patients that received pharmacologic thromboprophylaxis alone was 12,481. Of these patients, 1292 (10.4%) suffered VTE. The total number of patients that received GCS in conjunction with pharmacologic thromboprophylaxis was 1283. Of these patients, 75 had VTE (5.8%). Heterogeneity analysis demonstrated that the results of included study arms were significantly heterogeneous, precluding a valid summation analysis. CONCLUSIONS: The additional benefit of GCS to pharmacologic thromboprophylaxis in surgical inpatients is not clear on the basis of existing data. Further clinical trials directly evaluating this clinical question are recommended. PMID- 26992626 TI - Use of the Clinical, Etiologic, Anatomic, and Pathophysiologic classification and Venous Clinical Severity Score to establish a treatment plan for chronic venous disorders. AB - To be useful in clinical practice and in the evaluation of clinical therapies for chronic venous disorders, a measurement instrument should be objective, inclusive of all severities of venous disease, and rapidly performed by clinicians. The Clinical, Etiologic, Anatomic, and Pathophysiologic classification helps us identify the etiology, whether it is congenital, nonthrombotic, or post thrombotic; anatomic segments involved, whether deep, superficial, or perforators; and pathophysiologic data, such as reflux or obstruction. The Venous Clinical Severity Score can be used to observe patients longitudinally, especially after interventions, although the total score is biased with regard to advanced disease, such as C4 through C6. To be able to predict progression of disease, more patient-validated instruments are needed. Physician-reported outcomes (the Venous Clinical Severity Score and the Clinical, Etiologic, Anatomic, and Pathophysiologic classification) in association with a patient reported outcome may be the solution for the development of an ideal treatment plan. PMID- 26992627 TI - John Homans, MD, and the superficial femoral vein. PMID- 26992628 TI - Regarding "An overview of the most commonly used venous quality of life and clinical outcome measurements". PMID- 26992629 TI - Reply. PMID- 26992633 TI - Short-term preconditioning enhances the therapeutic potential of adipose-derived stromal/stem cell-conditioned medium in cisplatin-induced acute kidney injury. AB - The development of new strategies to preserve renal function after acute kidney injury (AKI) is necessary due to limited clinical intervention options. The organ protective effects of mesenchymal stromal/stem cells (MSCs) and their conditioned medium (CM) have been investigated demonstrating that both separately promoted tubular recovery and ameliorated the outcome of AKI. Nevertheless, strategies to optimise the regenerative potential of both are highly needed. Here we investigated the effects of CM from adipose-derived MSCs (ASCs) preincubated in a hypoxic environment (Hyp). Protective factors were investigated by PCR analysis and a protein array in vitro. The expression of 64 of the 308 proteins assayed was found to be more than two-fold increased after Hyp. CM of Hyp-pretreated ASCs (pCM) was used to enhance regeneration in a mouse model of cisplatin-induced AKI (cisAKI). Renal function was assessed by measurements of markers for AKI and serum cytokine levels. The pCM significantly ameliorated serum creatinine and neutrophil gelatinase-associated lipocalin values, and also the levels of inflammatory cytokines IL-1beta and IL-6 in the serum of mice with AKI. Our work clearly showed that a Hyp preconditioning significantly increases the release of protective factors in ASCs and enhances the therapeutic effects of CM in cisAKI in mice. PMID- 26992634 TI - Rituximab usage in systemic lupus erythematosus-associated antiphospholipid syndrome: A single-center experience. AB - OBJECTIVES: Although the data from primary antiphospholipid syndrome (APS) suggests a beneficial effect of rituximab usage, its therapeutic role remains to be defined in systemic lupus erythematosus (SLE)-associated APS, a complex clinical situation with thrombotic events and lupus activity. METHODS: A single center retrospective analysis of rituximab usages in APS was performed in 800 hospitalized SLE patients. RESULTS: There were 63 SLE-associated APS cases with 6 on rituximab therapy, all female aged 37.7 +/- 9.0 years with 1 catastrophic and 16 thrombotic episodes. Therapeutic indications included warfarin failure despite the adequate target international normalized ratio with an average duration of 17.3 +/- 11.2 months between the thrombotic recurrences. After the rituximab therapy, there was no relapse of thrombosis with a mean follow-up period of 39.3 +/- 20.9 months, and a decrease in lupus activity (SLEDAI-2K, 9.7 +/- 5.5 to 5.3 +/- 2.2). Infection complications were observed, including episodes of bronchitis and urinary tract infection. CONCLUSIONS: In this single-center study with largest case numbers and a long-term follow-up period, there were no recurrent thrombotic events after the rituximab therapy, implicating further consideration of large-scale trials enrolling more ethnic groups to evaluate its therapeutic role in SLE-associated APS patients. PMID- 26992635 TI - Streptococcus bovis septic arthritis and osteomyelitis: A report of 21 cases and a literature review. AB - BACKGROUND: The Streptococcus bovis group (SBG) is a well-known cause of endocarditis, but its role in osteoarticular infections (OAIs) has not been well described. METHODS: We analyzed all patients with OAIs by SBG diagnosed in our hospital (1988-2014). We selected those cases with septic arthritis and osteomyelitis, as defined according to clinical, microbiological, and imaging studies. Identification of the strains was performed by using the API 20 Strep and the GP card of the Vitek 2 system, and confirmed the identification by molecular methods. In addition, we reviewed the literature to select all cases of OAI by SBG during the period 1980-2015. RESULTS: From the 83 cases of OAI included in the analysis (21 from our center and 62 from the literature review), 59 were osteomyelitis (57 of them spondylodiscitis) and 24 were arthritis (2 with associated spondylodiscitis). The mean age was 66.9 years, and 79.2% of the patients were men. Endocarditis (IE) was associated with 59% of the cases and this association was greater for osteomyelitis than for arthritis (78.9% vs. 13.6%; P = 0.001). OAI was a presenting symptom in 63% of the cases of IE. Colonoscopy was performed in 64 cases, which detected colorectal neoplasm (CRN) in 46 patients (71.8%), almost all asymptomatic. Some 69.5% of these neoplasm were carcinomas or advanced adenomas. The blood cultures were positive in 78.3% cases. In 45 cases, the S. bovis species was identified; in 82.2% of the cases the cause was Streptococcus gallolyticus subsp. gallolyticus. The mortality was 7.2%, which in no case was attributable to the OAI. CONCLUSIONS: OAIs are frequently the initial manifestation of IE caused by SBG. S. gallolyticus causes most of these infections. Echocardiogram and colonoscopy are therefore mandatory, given the species' close association with IE and CRN. PMID- 26992636 TI - Survey and analysis of simple sequence repeats in the Ustilaginoidea virens genome and the development of microsatellite markers. AB - Ustilaginoidea virens is the causal agent of rice false smut, causing quantitative and qualitative losses in rice industry. However, the development and application of simple sequence repeat (SSR) markers for genetic diversity studies in U. virens were limited. This study is the first to perform large-scale development of SSR markers of this pathogen at the genome level, to (1) compare these SSR markers with those of other fungi, (2) analyze the pattern of the SSRs, and (3) obtain more informative genetic markers. U. virens is rich in SSRs, and 13,778 SSRs were identified with a relative abundance of 349.7SSRs/Mb. The most common motifs in the genome or in noncoding regions were mononucleotides, whereas trinucleotides in coding sequences. A total of 6 out of 127 primers were randomly selected to be used to analyze 115 isolates, and these 6 primers showed high polymorphism in U. virens. This study may serve as an important resource for molecular genetic studies in U. virens. PMID- 26992637 TI - MicroRNA-409-3p inhibits osteosarcoma cell migration and invasion by targeting catenin-delta1. AB - Osteosarcoma is the most common primary bone cancer which is associated with early metastatic potential and poor prognosis. However, the molecular mechanisms underlying osteosarcoma progression are not well characterized. Here, we investigated the role of miR-409-3p in osteosarcoma metastasis. Osteosarcoma tissue showed decreased expression of miR-409-3p compared to adjacent non tumorous tissue. The expression level of miR-409-3p was negatively correlated with osteosarcoma metastasis. Overexpression of miR-409-3p in osteosarcoma cells (U2OS) inhibited cell migration and invasion. Bioinformatics analysis showed that catenin-delta1 (CTNND1, p120-catenin) is a direct target of miR-409-3p. Overexpression of miR-409-3p repressed the expression of catenin-delta1 in U2OS cells at both mRNA and protein levels. Meanwhile, miR-409-3p repressed the activity of luciferase reporter containing the 3'-untranslated region (3'UTR) of CTNND1 gene. Furthermore, expression of catenin-delta1 rescued the inhibitory effect of miR-409-3p on cell migration and invasion. Altogether, these results indicated that miR-409-3p targets catenin-delta1 to repress osteosarcoma metastasis. PMID- 26992638 TI - Identification of PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) as an essential gene for colorectal cancer (CRCs) cells. AB - Oncogene and non-oncogene addictions describe the phenomenon that tumor cells become reliant on certain genes for maintenance of malignancy. Reversal of these mutations profoundly affects tumor growth and survival, providing a fundamental rationale for development of targeted cancer therapy. However, inadequate knowledge on cancer signaling networks and lack of potential drug targets limited its clinical application. A screen was conducted using a custom small interfering RNA (siRNA) library in colorectal cancer (CRC). Transient knockdown followed by cell proliferation assays were performed to validate the essentiality of PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) in CRC. Western blot analysis was performed to examine the mechanism by which PRKDC confers selective survival advantage in CRC cells. Inducible knockdown and overexpression cell lines were introduced into nude mice to assess PRKDC dependency of CRC cells in vivo. PRKDC expression level in patient samples and overall survival of patients with low or high PRKDC expression were analyzed. Transient knockdown of PRKDC reduced cell proliferation/survival in HCT116 and DLD1, but not FHC cells. PRKDC down-regulation induced apoptosis partially through inhibiting AKT activation, and sensitized HCT116 cells to chemotherapeutic agents interfering with DNA replication. Inducible knockdown of PRKDC inhibited tumor growth in vivo. PRKDC was up-regulated in cancerous tissues compared with normal tissues. Patients with high PRKDC expression showed poorer overall survival. PRKDC is an essential gene required for CRC cell proliferation/survival, which may represent as a potential prognostic biomarker and an ideal therapeutic target for CRC. PMID- 26992639 TI - MicroRNA-29a-3p attenuates ET-1-induced hypertrophic responses in H9c2 cardiomyocytes. AB - Transcription factor nuclear factor of activated T cells c4 (NFATc4) is the best characterized target for the development of cardiac hypertrophy. Aberrant microRNA-29 (miR-29) expression is involved in the development of cardiac fibrosis and congestive heart failure. However, whether miR-29 regulates hypertrophic processes is still not clear. In this study, we investigated the potential functions of miR-29a-3p in endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. We showed that miR-29a-3p was down-regulated in ET-1-treated H9c2 cardiomyocytes. Overexpression of miR-29a-3p significantly reduced ET-1-induced hypertrophic responses in H9c2 cardiomyocytes, which was accompanied by a decrease in NFATc4 expression. miR-29a-3p targeted directly to the 3'-UTR of NFATc4 mRNA and silenced NFATc4 expression. Our results indicate that miR-29a-3p inhibits ET-1-induced cardiomyocyte hypertrophy via inhibiting NFATc4 expression. PMID- 26992640 TI - Development and application of a new Silent reporter system to quantitate the activity of enhancer elements in the type II Collagen Gene. AB - Type II collagen is a major component of cartilage, which provide structural stiffness to the tissue. As a sufficient amount of type II collagen is critical for maintaining the biomechanical properties of cartilage, its expression is tightly regulated in chondrocytes. Therefore, it is essential to elucidate in detail the transcriptional mechanism that controls expression of type II collagen, in particular by two enhancer elements we recently discovered. To systematically analyze and compare enhancer activities, we developed a novel reporter assay system that exploits site-specific integration of promoter and enhancer elements to activate a transcriptionally silent reporter gene. Using this system, we found that the enhancer elements have distinct characteristics, with one exhibiting additive effects and the other exhibiting synergistic effects when repeated in tandem. PMID- 26992641 TI - A rare case of double parathyroid adenoma evidenced by 99mTc-sestaMIBI SPECT/CT. PMID- 26992642 TI - Contribution of brain perfusion SPECT in the diagnosis of a case of cerebral malaria. AB - Cerebral malaria is a serious complication of infection with Plasmodium falciparum. Its pathophysiological mechanisms and clinical manifestations are still currently being studied. Structural imaging techniques such as CT and MRI provide non-specific information during the diagnostic process. However, there are hardly any references on the use and potential benefits of radioisotope procedures for this pathology. In this article we present the case of a patient diagnosed with cerebral malaria treated in our centre, subjected to progressive monitoring using SPECT perfusion. PMID- 26992643 TI - Pediatric transport medicine and the dawn of the pediatric anesthesiology and critical care medicine subspecialty: an interview with pioneer Dr. Alvin Hackel. AB - Dr. Alvin 'Al' Hackel (1932-) Professor Emeritus of Anesthesiology, Perioperative and Pain Medicine, and Pediatrics at the Stanford University School of Medicine, has been an influential pioneer in shaping the scope and practice of pediatric anesthesia. His leadership helped to formally define the subspecialty of pediatric anesthesiology ('who is a pediatric anesthesiologist?') and the importance of specialization and regionalization of expertise in both patient transport and perioperative care. His enduring impact on pediatric anesthesia and critical care practice was recognized in 2006 by the American Academy of Pediatrics when it bestowed upon him the profession's highest lifetime achievement award, the Robert M. Smith Award. Of his many contributions, Dr. Hackel identifies his early involvement in the development of pediatric transport medicine as well as the subspecialty of pediatric anesthesiology as his defining contribution. Based on a series of interviews held with Dr. Hackel between 2009 and 2014, this article reviews the early development of transportation medicine and the remarkable career of a pioneering pediatric anesthesiologist. PMID- 26992648 TI - Occupation and first episode psychosis in Northern Italy: better outcomes for migrants. AB - AIMS: Many studies show that migrants have a higher incidence of psychosis compared to natives, but the influence of migration on psychosis outcomes is little investigated. We aimed to evaluate the occupational outcomes of a first episode psychosis (FEP) sample in Bologna (Northern Italy). METHODS: An incidence cohort of FEP patients presenting at the Bologna West Community Mental Health Centers between 2002 and 2009 was assessed at the baseline and at 12th month follow-up. Return to school or work was used as occupational outcome. RESULTS: Most of the patients (82.8%) were still in contact at 12 months. Migrants showed significantly higher rate of return to work compared to natives (adjusted OR 4.45, 95% CI 1.55-12.76). CONCLUSIONS: First generation migrants had better occupational outcomes. Further cross-cultural studies are needed to further explain these findings. PMID- 26992649 TI - Does root canal treatment in necrotic pulp or retreatment cases with periapical lesions require anaesthesia? An in vivo clinical study. AB - AIM: To examine whether local anaesthesia is required for treating teeth with necrotic pulps (TNP) and retreatment cases (RCs) associated with periapical lesions. METHODOLOGY: Root canal treatment was performed in TNP and RCs without the administration of local anaesthesia. Patients were assured that if they experienced pain, local anaesthesia would be provided. Eighty canals, 40 TNP and 40 RCs, were included in the study. Two length measurements were performed: one using an electronic apex locator (EAL), which was defined as the electronic length (EL), and the second, the length at which the patient first reported that a size 15 file was touching the periapical tissues, which was defined as the periodontal length (PL). The difference between these two measurements (Delta = PL - EL) was the parameter studied. Statistical analysis was conducted using two way anova and paired t-tests. Working length (WL) was defined in this study as being 0.5 mm short of the EL. RESULTS: EL was shorter than PL in 96% of cases. The mean difference between measurements was 0.78 (+/-0.11) mm in the TNP group and 0.63 (+/-0.15) mm in the RC group; the difference was not significant. The distances between the WL and PL were thus 1.28 and 1.13 mm, respectively. In none of the 80 canals did the patient experience any pain, either during the measurements or during the instrumentation procedures. CONCLUSIONS: When EALs are used, local anaesthesia may not be required for root canal treatment in teeth with necrotic pulps and retreatment cases associated with periapical lesions. PMID- 26992650 TI - Update in achalasia: what the surgeon needs to know. AB - Achalasia is a motility disorder encountered by surgeons during the investigation and treatment of dysphagia. Recent advances in manometry technology, a widely accepted new classification system and a new treatment rapidly gaining international acceptance, have changed the working knowledge required to successfully manage patients with achalasia. We review the Chicago classification subtypes of achalasia with type II achalasia being a predictor of success and type III achalasia a predictor of treatment failure. We review per-oral endoscopic myotomy as an emerging treatment option and its potential for improving the treatment of type III achalasia. PMID- 26992651 TI - Clues for discovering a new biological function of Vitreoscilla hemoglobin in organisms: potential sulfide receptor and storage. AB - The interaction between H2 S and Vitreoscilla hemoglobin (VHb) has been studied by UV-Vis and Resonance Raman spectroscopes to confirm the binding between the ligand and the protein. Kinetic constants, kon = 1.2 * 10(5) m(-1) .s(-1) and koff = 2.5 * 10(-4) .s(-1) , have been determined and compared with those for mammalian hemoglobins. Density Functional Theory study supports the binding of H2 S by modeling the configurations of HOMO dispersions. We hypothesized that VHb is involved in H2 S reception and storage. Different from Lucina pectinata HbI, a typical H2 S-binding hemoglobin, VHb, exhibits unusual properties on H2 S reactivity such as steric constraints playing an important role in modulating H2 S entry. A distinct mechanism of VHb interaction with H2 S is supported by studies of variant forms of VHb. PMID- 26992652 TI - Virtual reality training in laparoscopic surgery: A systematic review & meta analysis. AB - INTRODUCTION: Laparoscopic surgery requires a different and sometimes more complex skill set than does open surgery. Shortened working hours, less training times, and patient safety issues necessitates that these skills need to be acquired outside the operating room. Virtual reality simulation in laparoscopic surgery is a growing field, and many studies have been published to determine its effectiveness. AIMS: This systematic review and meta-analysis aims to evaluate virtual reality simulation in laparoscopic abdominal surgery in comparison to other simulation models and to no training. METHODS: A systematic literature search was carried out until January 2014 in full adherence to PRISMA guidelines. All randomised controlled studies comparing virtual reality training to other models of training or to no training were included. Only studies utilizing objective and validated assessment tools were included. RESULTS: Thirty one randomised controlled trials that compare virtual reality training to other models of training or to no training were included. The results of the meta analysis showed that virtual reality simulation is significantly more effective than video trainers, and at least as good as box trainers. CONCLUSION: The use of Proficiency-based VR training, under supervision with prompt instructions and feedback, and the use of haptic feedback, has proven to be the most effective way of delivering the virtual reality training. The incorporation of virtual reality training into surgical training curricula is now necessary. A unified platform of training needs to be established. Further studies to assess the impact on patient outcomes and on hospital costs are necessary. (PROSPERO Registration number: CRD42014010030). PMID- 26992653 TI - Purification of mumps virus particles of high viability. AB - Mumps is a highly infectious viral disease of humans with a wide array of clinical manifestations ranging from painful swelling of the salivary glands to meningitis and encephalitis. Despite the clinical importance of mumps virus, most of what is known of its biological properties comes from studies using supernatants from virus infected cell cultures, which contain substantial levels of host cell derived debris and biologically active substances such as cytokines, transcription factors and secreted virus proteins. These contaminants complicate interpretation of studies of virus replication, virus-host interactions and in vivo virulence. Here we describe a protocol for concentration of the virus from cell culture supernatants followed by gradient purification, resulting in attainment of high titer live virus of high purity. PMID- 26992654 TI - Characterization and epitope mapping of monoclonal antibodies raised against rat hepatitis E virus capsid protein: An evaluation of their neutralizing activity in a cell culture system. AB - Hepatitis E virus (HEV) is the causative agent of acute hepatitis. Rat HEV is a recently discovered virus related to, but distinct from, human HEV. Since laboratory rats can be reproducibly infected with rat HEV and a cell culture system has been established for rat HEV, this virus may be used as a surrogate virus for human HEV, enabling studies on virus replication and mechanism of infection. However, monoclonal antibodies (MAbs) against rat HEV capsid (ORF2) protein are not available. In this study, 12 murine MAbs were generated against a recombinant ORF2 protein of rat HEV (rRatHEV-ORF2: amino acids 101-644) and were classified into at least six distinct groups by epitope mapping and a cross reactivity analysis with human HEV ORF2 proteins. Two non-cross-reactive MAbs recognizing the protruding (P) domain detected both non-denatured and denatured rRatHEV-ORF2 protein and efficiently captured cell culture-produced rat HEV particles that had been treated with deoxycholate and trypsin, but not those without prior treatment. In addition, these two MAbs were able to efficiently neutralize replication of cell culture-generated rat HEV particles without lipid membranes (but not those with lipid membranes) in a cell culture system, similar to human HEV. PMID- 26992656 TI - Bactericidal activity of biomimetic diamond nanocone surfaces. AB - The formation of biofilms on implant surfaces and the subsequent development of medical device-associated infections are difficult to resolve and can cause considerable morbidity to the patient. Over the past decade, there has been growing recognition that physical cues, such as surface topography, can regulate biological responses and possess bactericidal activity. In this study, diamond nanocone-patterned surfaces, representing biomimetic analogs of the naturally bactericidal cicada fly wing, were fabricated using microwave plasma chemical vapor deposition, followed by bias-assisted reactive ion etching. Two structurally distinct nanocone surfaces were produced, characterized, and the bactericidal ability examined. The sharp diamond nanocone features were found to have bactericidal capabilities with the surface possessing the more varying cone dimension, nonuniform array, and decreased density, showing enhanced bactericidal ability over the more uniform, highly dense nanocone surface. Future research will focus on using the fabrication process to tailor surface nanotopographies on clinically relevant materials that promote both effective killing of a broader range of microorganisms and the desired mammalian cell response. This study serves to introduce a technology that may launch a new and innovative direction in the design of biomaterials with capacity to reduce the risk of medical device associated infections. PMID- 26992655 TI - Patients on state organ donor registries receive similar levels of intensive care compared to those who are not: an opportunity to increase public intent to donate. AB - The intent to donate organs is affected by the public perception that patients on state registries receive less aggressive life-saving care in order to allow organ donation to proceed. However, the association between first person authorization to donate organs and the actual care received by eventual organ donors in hospitals is unknown. From August 2010 to April 2011, all eight organ procurement organizations in United Network for Organ Sharing Region 5 prospectively recorded demographic data and organ utilization rates on all donors after neurologic determination of death (DNDDs). Critical care and physiologic parameters were also recorded at referral for imminent neurologic death and prior to authorization for donation to reflect the aggressiveness of provided care. There were 586 DNDDs and 23% were on a state registry. Compared to non-registered DNDDs, those on state registries were older but were noted to have similar critical care parameters at both referral and authorization. Furthermore, there was no significant difference in organs procured per donor or organs transplanted per donor between registered and non-registered DNDDs. Thus, DNDDs who are on state donor registries receive similar levels of intensive care compared to non registered donors. The association noted in this study may therefore help to dispel a common misperception that decreases the intent to donate. PMID- 26992657 TI - The metabolic profiles of pterin compounds as potential biomarkers of bladder cancer-Integration of analytical-based approach with biostatistical methodology. AB - Cancer disease is the second leading cause of death across the world. The analysis of potential biomarkers of cancer can be useful in cancer screening or cancer diagnosis, and may provide valuable information on the disease risk and progression. Pterin compounds have been studied as candidates of potential biomarkers as their elevated levels have been reported in various cancer diseases. The objective of the study was to compare the profiles of six pterin compounds in urine of 35 healthy subjects and 46 patients diagnosed of bladder cancer with the use of HPLC coupled with fluorimetric detection. The results of the chromatographic analysis together with biostatistical-based approach showed, that the concentrations of pterin compounds in bladder cancer patients were higher as compared to healthy individuals, and statistically significant differences between patients and controls were reported for xanthopterin and isoxanthopterin. Moreover, gender-specific analysis revealed, that the concentrations of pterins in the group of women reached higher values in comparison to men. For metabolites juxtaposed in pairs, namely xanthopterin and isoxanthopterin as well as for neopterin and biopterin, we found significant positive correlations in the group of both, patients and healthy individuals. We therefore conclude, that chromatographic analysis with simultaneous extensive biostatistical-based interpretation of the metabolite profiles may provide deeper understanding of the relationships between pterin metabolites. The results do not prejudge the possibility of using pterin compounds in the diagnosis of bladder tumors. However the results may have an impact on the study of bladder cancer biomarkers. PMID- 26992658 TI - Investigation of serum vitamin D levels in Chinese infertile men. AB - Recently, the question of whether vitamin D exerts an effect on the pathogenic process of infertility has become the centre of attention. There are some controversial conclusions on this issue. Based on previous studies, we sought to explore the difference of serum 25-hydroxyvitamin D3 , 1,25-dihydroxyvitamin D3 levels between infertile patients and fertile men, and to find the influence on semen quality. The analysis of serum 25-hydroxyvitamin D3 level showed no significant difference between infertile patients and fertile men. However, the levels of serum 1,25-dihydroxyvitamin D3 in oligospermia (P < 0.05), asthenospermia (P < 0.01), oligoasthenospermia (P < 0.05) and azoospermia (P < 0.01) patients were significantly lower than those in fertile men. Moreover, serum 1,25-dihydroxyvitamin D3 level was positively correlated with progressive motility and total sperm number in infertile patients. In addition, a positive correlation between serum prolactin and 1,25-dihydroxyvitamin D3 was observed in fertile men. Our results indicated that lower vitamin D could be a risk factor for poor semen quality in infertile men. The 1,25-dihydroxyvitamin D3 , as the biologically active form of vitamin D, may be more significant. PMID- 26992659 TI - Primary and secondary effects of real-time feedback to reduce vertical loading rate during running. AB - Gait modifications are often proposed to reduce average loading rate (AVLR) during running. While many modifications may reduce AVLR, little work has investigated secondary gait changes. Thirty-two rearfoot runners [16M, 16F, 24.7 (3.3) years, 22.72 (3.01) kg/m2 , >16 km/week] ran at a self-selected speed (2.9 +/- 0.3 m/s) on an instrumented treadmill, while 3D mechanics were calculated via real-time data acquisition. Real-time visual feedback was provided in a randomized order to cue a forefoot strike (FFS), a minimum 7.5% decrease in step length, or a minimum 15% reduction in AVLR. AVLR was reduced by FFS (mean difference = 26.4 BW/s; 95% CI = 20.1, 32.7; P < 0.001), shortened step length (8.4 BW/s; 95% CI = 2.9, 14.0; P = 0.004), and cues to reduce AVLR (14.9 BW/s; 95% CI = 10.2, 19.6; P < 0.001). FFS, shortened step length, and cues to reduce AVLR all reduced eccentric knee joint work per km [(-48.2 J/kg*m; 95% CI = -58.1, -38.3; P < 0.001), (-35.5 J/kg*m; 95% CI = -42.4, 28.6; P < 0.001), (-23.1 J/kg*m; 95% CI = -33.3, -12.9; P < 0.001)]. However, FFS and cues to reduce AVLR also increased eccentric ankle joint work per km [(54.49 J/kg*m; 95% CI = 45.3, 63.7; P < 0.001), (9.20 J/kg*m; 95% CI = 1.7, 16.7; P = 0.035)]. Potentially injurious secondary effects associated with FFS and cues to reduce AVLR may undermine their clinical utility. Alternatively, a shortened step length resulted in small reductions in AVLR, without any potentially injurious secondary effects. PMID- 26992661 TI - Sarolaner-a novel isoxazoline-addresses the need for enhanced flea and tick control. PMID- 26992660 TI - Oral administration of beta-carotene or lycopene prevents atopic dermatitis-like dermatitis in HR-1 mice. AB - Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease. Certain populations of patients are resistant to standard therapies with topical steroids and/or calcineurin inhibitors, and require systemic medication, such as immunosuppressants. Recently, several reports have shed light on the anti allergic effects of carotenoids. Therefore, we investigated the effect of p.o. administration of beta-carotene or lycopene on AD-like symptoms of HR-1 hairless mice fed with a low zinc/magnesium diet. Mice were divided into four groups: (i) fed with a standard diet (Co group); (ii) low zinc/magnesium diet (HR group); (iii) low zinc/magnesium and beta-carotene diet (HR-C group); and (iv) low zinc/magnesium and lycopene diet (HR-L group). They were then fed these diets for 8 weeks. Severities of dermatitis were assessed by their appearance, and histopathological and hematological observations. Mice in the HR group developed AD-like dermatitis both clinically and histologically. HR-C and HR-L group mice also developed xerosis and wrinkle-like skin changes, but they were milder than those of HR group mice. Histological analysis revealed that epidermis thickening and inflammatory cell infiltration in the skin of the HR-C and HR-L groups were both statistically less than those of the HR group. The concentration of thymus and activation regulated chemokine in the skin of the HR-L group and the concentration of CCL27 in the skin of the HR-C group were significantly lower than those of the HR group, respectively. In conclusion, p.o. administration of beta-carotene or lycopene prevents AD-like symptoms in association with a suppression of T-helper 2 chemokines in a murine model. Ingestion of carotenoids may be beneficial for patients with AD. PMID- 26992662 TI - Dual Antiplatelet Therapy Duration: A Review of Current Available Evidence. AB - PURPOSE: Multiple regimens of antiplatelet and anticoagulation therapy have been used in the past in patients undergoing percutaneous coronary intervention (PCI). Later trials of PCI stenting demonstrated the efficacy of dual-antiplatelet therapy (DAPT) in reducing stent- and non-stent-related thrombotic events in this specific population. Nonetheless, the required duration of DAPT has not yet been elucidated. In this article we sought to identify various randomized clinical trials (RCTs), pooled analyses, meta-analyses, and data pertaining to the optimal duration of DAPT and attempt some recommendations based on patients' clinical and procedural profiles. METHODS: We performed an extensive search using MEDLINE, Scopus, Cochrane Library, and Internet sources for abstracts, manuscripts, and conference reports without any language or date restrictions. In our review we included all available evidence from RCTs, meta-analyses, observational studies, and abstracts pertaining to our topic. Search results that were deemed irrelevant or that would not serve the goal or topic of our review were excluded. RESULTS: Our search yielded 10 RCTs directly comparing different durations of DAPT, 3 meta analyses amassing the evidence resulting from randomized data, and numerous observational studies that served the aim of our review. The observational studies included in the manuscript are directly related to instances in which RCTs could not be performed or introduce important concepts related to the duration of DAPT. IMPLICATIONS: There is no conclusive evidence that determines the mandatory DAPT duration after PCI. In addition, there are distinct patient populations that need specific treatment regimens, such as diabetic patients or those on long-term oral anticoagulation. Therefore, clinical judgement and meticulous examination of all pertaining risk factors are required for each individual. These factors include those related to a patient's characteristics, treatment procedures, lesion complexity, and stent type. Currently ongoing studies are anticipated to further elucidate and integrate our understanding with regard to DAPT. PMID- 26992663 TI - Potential Therapeutic Aspects of Alarmin Cytokine Interleukin 33 or Its Inhibitors in Various Diseases. AB - PURPOSE: The purpose of this review was to examine the comprehensively accumulated data regarding potential therapeutic aspects of exogenous administration of interleukin 33 (IL-33) or its antagonists in allergic, cancerous, infectious, and inflammatory diseases. METHODS: A selected review was undertaken of publications that examined the protective and exacerbating effects of IL-33 or its inhibitors in different diseases. Mechanisms of action are summarized to examine the putative role of IL-33 in various diseases. FINDINGS: IL-33 promoted antibacterial, antiviral, anti-inflammatory, and vaccine adjuvant functions. However, in TH2-biased respiratory, allergic, parasitic, and inflammatory conditions, IL-33 exhibited disease-sensitizing effects. The alarmin cytokine IL-33 induced protective effects in diseases via recruitment of regulatory T cells; antiviral CD8(+) cells, natural killer cells, gammadelta T cells, and nuocytes; antibacterial and antifungal neutrophils or macrophages; vaccine-associated B/T cells; and inhibition of nuclear factor-kappaB-mediated gene transcription. In contrast, IL-33 exacerbated the disease process by increasing TH2 cytokines, IgE and eosinophilic immune responses, and inhibition of leukocyte recruitment in various diseases. IMPLICATIONS: The protective or exacerbated aspects of use of IL-33 or its inhibitors are dependent on the type of infection or inflammatory condition, duration of disease (acute or chronic), organ involved, cytokine microenvironment, dose or kinetics of IL-33, and genetic predisposition. The alarmin cytokine IL-33 acts at cellular, molecular, and transcriptional levels to mediate pluripotent functions in various diseases and has potential therapeutic value to mitigate the disease process. PMID- 26992664 TI - Validation of a Patient-reported Outcome (PRO) Measure and a Clinician-reported Outcome (CRO) Measure to Assess Satisfaction with Pharmacologic Stress Agents for Single-photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging (MPI). AB - PURPOSE: The objective of this study was to develop and validate clinician and patient measures of satisfaction for pharmacologic stress agents (PSAs) used in single-photon emission computed tomography myocardial perfusion imaging procedures. METHODS: Two questionnaires were developed: the Clinician Satisfaction and Preference Questionnaire (CSPQ) and the Patient Satisfaction and Preference Questionnaire (PSPQ). Items were developed, and the content validity of the questionnaires was ensured by participants' involvement in the item generation (5 clinician and 18 patient face-to-face concept elicitation interviews) and item modification phases (5 clinician and 10 patient face-to-face cognitive debriefing interviews). Psychometric validation of the satisfaction component of the questionnaires was conducted in a sample of 9 clinicians and 90 patients. FINDINGS: After initial patient interviews and cognitive interviews, two 8-item instruments were developed with each containing an optional PSA preference question. The PSPQ assessed patients' receptiveness and satisfaction with the PSA that they received. The CSPQ assessed clinicians' satisfaction with the time and ease of PSA preparation, administration, and monitoring of the PSA. The optional preference question in both instruments assesses preference among PSAs. In a multicenter observational study of 88 patients and 9 clinicians, the PSPQ Preparation and Reaction to Agent scales elicited reliability coefficients of 0.90 and 0.87, respectively. In addition, the test-retest reliability was acceptable for all PSPQ scales (intraclass correlation coefficient range, 0.73 0.86). Concurrent validity with the Treatment Satisfaction Questionnaire for Medication (TSQM) indicates low-to-moderate correlations between the Effectiveness, Convenience, and Global Satisfaction scales of the TSQM with the PSPQ Satisfaction with Administration, Satisfaction with Effects, and Overall Satisfaction items (range, 0.46-0.78). Analysis of the CSPQ found that both the Preparation and Reaction to Agent subscales indicated strong internal consistency (alpha = 0.98 and 0.99, respectively). IMPLICATIONS: The PSPQ and CSPQ were developed and validated with rigorous methods. The instruments and their domains found strong internal consistency and good test-retest reliability. These questionnaires, when used as measures of treatment satisfaction in clinical trials, real-world observational studies, or by clinicians in their own laboratories, may help patients and clinicians better understand the impact of single-photon emission computed tomography myocardial perfusion imaging pharmacologic stress testing. PMID- 26992665 TI - Does the association between ADHD and pediatric epilepsy signal a tolerance continuum to human environmental exposures? A reply to Salpekar and Mishra (2014). PMID- 26992666 TI - Calcium carbonate-based permeable reactive barriers for iron and manganese groundwater remediation at landfills. AB - High concentrations of iron (Fe(II)) and manganese (Mn(II)) reductively dissolved from soil minerals have been detected in groundwater monitoring wells near many municipal solid waste landfills. Two in situ permeable reactive barriers (PRBs), comprised of limestone and crushed concrete, were installed downgradient of a closed, unlined landfill in Florida, USA, to remediate groundwater containing high concentrations of these metals. Influent groundwater to the PRBs contained mean Fe and Mn concentrations of approximately 30mg/L and 1.62mg/L, respectively. PRBs were constructed in the shallow aquifer (maximum depth 4.6m below land surface) and groundwater was sampled from a network of nearby monitoring wells to evaluate barrier performance in removing these metals. PRBs significantly (p<0.05) removed dissolved Fe and Mn from influent groundwater; Fe was removed from influent water at average rates of 91% and 95% (by mass) for the limestone and crushed concrete PRBs, respectively, during the first year of the study. The performance of the PRBs declined after 3years of operation, with Fe removal efficiency decreasing to 64% and 61% for limestone and concrete PRBs, respectively. A comparison of water quality in shallow and deep monitoring wells showed a more dramatic performance reduction in the deeper section of the concrete PRB, which was attributed to an influx of sediment into the barrier and settling of particulates from the upper portions of the PRBs. Although removal of Fe and Mn from redox impacts was achieved with the PRBs, the short time frame of effectiveness relative to the duration of a full-scale remediation effort may limit the applicability of these systems at some landfills because of the construction costs required. PMID- 26992667 TI - Decreased placental and maternal serum TRAIL-R2 levels are associated with placenta accreta. AB - OBJECTIVES: TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) is produced both by decidual and trophoblast cells during pregnancy and known to participate in apoptosis. In this study, we aimed to determine and to compare maternal serum and placental TRAIL-R2 levels in patients with placenta accreta, non-adherent placenta previa and in healthy pregnancies. We also aimed to analyze the association of placenta accreta with the occurrence of previous C-sections. STUDY DESIGN: A total of 82 pregnant women were enrolled in this case-control study (27 placenta accreta patients, 26 non-adherent placenta previa patients and 29 age-, and BMI-matched healthy, uncomplicated pregnant controls). TRAIL-R2 levels were studied in both maternal serum and placental tissue homogenates. Determining the best predictor(s) which discriminate placenta accreta was analyzed by multiple logistic regression analyses. Adjusted odds ratios and 95% confidence intervals were also calculated. RESULTS: Both placental and serum TRAIL-R2 levels were significantly lower in placenta accreta group (median 34.82 pg/mg and 19.85 pg/mL, respectively) when compared with both non-adherent placenta previa (median 39.24 pg/mg and 25.99 pg/mL, respectively) and the control groups (median 41.62 pg/mg and 25.87 pg/mL, respectively) (p < 0.05). Placental TRAIL-R2 levels and previous cesarean section were found to be significantly associated with placenta accreta (OR: 0.934 95% CI 0.883-0.987, p = 0.016 and OR:7.725 95% CI: 2.717-21.965, p < 0.001, respectively). Placental and serum TRAIL-R2 levels were positively correlated. CONCLUSION: Decreased levels of placental TRAIL-R2 and previous history of cesarean section were found to be significantly associated with placenta accreta, suggesting a possible role of apoptosis in abnormal trophoblast invasion. PMID- 26992668 TI - Identification of suitable reference genes in the mouse placenta. AB - INTRODUCTION: Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) is a reliable tool to analyse gene expression profiles. The expression of housekeeping genes generally serves as a reference for mRNA amount, assuming that it remains stable under pathophysiological and experimental conditions. To date, an empirical validation of reference genes suitable for RT qPCR-based studies in the mouse placenta is missing. METHODS: We used NormFinder and BestKeeper statistical software to analyse the expression stability of candidate housekeeping genes quantified by RT-qPCR in mouse placentas. RESULTS: Fifteen of 32 potential candidate housekeeping genes analysed on gestation day (gd) 16.5 in mouse placentas exhibited an optimal cycle threshold (Ct). Among them B2m, Polr2a, Ubc, and Ywhaz genes showed the highest expression stability in placentas from control, but also experimentally-challenged mice. These genes as well as the currently widely used housekeeping genes Hprt1, Actb, and Gapdh were selected for further quality assessments. We quantified the Ct values of these selected genes in placental samples obtained from wild-type or genetically engineered dams at different gds, or upon selected experimental interventions known to affect placental phenotype. Among all housekeeping genes analysed, Polr2a was the most stably expressed and its expression stability excelled in combination with Ubc. DISCUSSION: Polr2a, especially in combination with Ubc, can be proposed as highly suitable endogenous reference for gene expression analysis in mouse-derived placental tissue. Moreover, the validation of both genes as a stable reference gene in human placenta-derived tissue strengthens the translational relevance of RT-qPCR findings using mouse placenta. PMID- 26992669 TI - Reduced placental oxygenation during subclinical uterine contractions as assessed by BOLD MRI. AB - OBJECTIVES: During placental Blood Oxygen Level Dependent (BOLD) Magnetic Resonance Imaging (MRI), we have observed spontaneous reductions in placental oxygenation lasting 2-4 min. We hypothesize, that these reductions in placental oxygenation are caused by subclinical uterine contractions. METHODS: We evaluated placental oxygenation during a five-minute placental BOLD MRI in 56 normal pregnancies (gestational week 23-40) and observed a spontaneous reduction in eight cases. The 56 BOLD MRIs were systematically analyzed for signs of uterine contractions, i.e. visual changes in uterus shape and reductions in the number of pixels within Regions of interest (ROI) covering the outline of the entire uterus. RESULTS: The eight reductions in the BOLD signal lasted for 217 +/- 51 (mean +/- SD) seconds with an average signal loss of 17 +/- 5%. They were all associated with a contraction, which started 43 +/- 21 s prior to the start of the reduction and ended 71 +/- 30 s prior to the end of the reduction. In the remaining 48 MRIs, we observed no contraction. CONCLUSION: We suggest that the observed spontaneous reductions in placental oxygenation are caused by uterine contractions. According to our data, subclinical uterine contractions occur regularly and have a markedly impact on placental oxygenation. Therefore, uterine contractions need to be considered in the interpretation of placental MRI as they may interfere with the MRI results. PMID- 26992670 TI - Telomere homeostasis in IUGR placentas - A review. AB - Telomeres are nucleoprotein structures located at the termini of chromosomes. They are essential for chromosome stability. Telomeres become shorter due to mitotic cycles and environmental factors. When telomeres are shortened and therefore dysfunctional, cellular senescence occurs and organ dysfunction might develop. During pregnancy, fetal growth restriction secondary to placental insufficiency has been linked to impaired telomere homeostasis in which telomeres are shorter, telomerase is decreased, and compensatory mechanisms of telomere capture are enhanced. These characteristics, along with increased signs of senescence, indicate telomere dysfunction in trophoblasts from placentas affected by intrauterine growth restriction (IUGR). This review summarizes the information currently available regarding telomere homeostasis in trophoblasts from human pregnancies affected by IUGR. Improved understanding of placental physiology might help in the development of treatment options for fetuses with IUGR. PMID- 26992671 TI - Isolation of basal membrane proteins from BeWo cells and their expression in placentas from fetal growth-restricted pregnancies. AB - INTRODUCTION: The syncytiotrophoblast, a key barrier between the mother and fetus, is a polarized epithelium composed of a microvillus and basal membrane (BM). We sought to characterize BM proteins of BeWo cells in relation to hypoxia and to investigate their expression in placentas from pregnancies complicated by fetal growth restriction (FGR). METHODS: We isolated the BM fraction of BeWo cells by the cationic colloidal silica method and identified proteins enriched in this fraction by mass spectrometry. We evaluated the effect of hypoxia on the expression and intracellular localization of identified proteins and compared their expression in BM fractions of FGR placentas to those from normal pregnancies. RESULTS: We identified BM proteins from BeWo cells. Among BM proteins, we further characterized heme oxygenase-1 (HO-1), voltage-dependent anion channel-1 (VDAC1), and ribophorin II (RPN2), based on their relevance to placental biology. Hypoxia enhanced the localization of these proteins to the BM of BeWo cells. HO-1, VDAC1, and RPN2 were selectively expressed in the human placental BM fraction. C-terminally truncated HO-1 was identified in placental BM fractions, and its BM expression was significantly reduced in FGR placentas than in normal placentas. Interestingly, a truncated HO-1 construct was predominantly localized in the BM in response to hypoxia and co-localized with VDAC1 in BeWo cells. DISCUSSION: Hypoxia increased the BM localization of HO-1, VDAC1, and RPN2 proteins. FGR significantly reduced the expression of truncated HO-1, which was surmised to co-localize with VDAC1 in hypoxic BeWo cells. PMID- 26992672 TI - Maternal obesity induced by a 'cafeteria' diet in the rat does not increase inflammation in maternal, placental or fetal tissues in late gestation. AB - INTRODUCTION: Obesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation. METHODS: Maternal obesity was established in rats by 8 weeks of pre pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1beta, IL-6, IL 10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFalpha) and expression of inflammatory genes (Tnfalpha, Il-6, Il-1beta, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation. RESULTS: Despite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL 6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver. CONCLUSIONS: Maternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation. PMID- 26992673 TI - Maternal obesity alters the apelinergic system at the feto-maternal interface. AB - Apelin and its receptor APJ have been implicated in pathologies including cardiovascular disease, diabetes and obesity. Little is known about the function of the apelinergic system during gestation. We evaluated in mice this system at the feto-maternal interface in insulin-resistant obese female (HF) mice. Maternal apelinemia was decreased at term and fetal apelinemia was sixfold higher than maternal level. Ex-vivo, the placenta releases apelin at E12.5 and E18.5. In HF pregnant mice at term, apelinemia as well as placental apelin and APJ mRNA levels were increased whereas placental release of apelin was drastically reduced compared to controls. PMID- 26992674 TI - Twist1 is involved in trophoblast syncytialization by regulating GCM1. AB - INTRODUCTION: The multinucleated syncytiotrophoblast (STB) is maintained and regenerated by the fusion of underlying cytotrophoblast cells (CTBs) and is responsible for a number of functions in the human placenta. Deficiencies in this structure may result in pregnancy-associated diseases. However, the detailed mechanisms underlying trophoblast syncytialization await further investigation. METHODS: The location of the transcription factor Twist1 in human placental tissues was identified by immunohistochemistry. The expression of Twist1 and glial cells missing-1 (GCM1) was evaluated by qPCR or western blotting in two cell-fusion models including forskolin-induced fusion of BeWo cells and spontaneous syncytialization of CTBs. The key role of Twist1 in trophoblast differentiation was identified using BeWo cells transfected with Twist1-specific siRNA. We investigated the effect of hypoxia on the expression of Twist1 and GCM1 in primary CTBs cultured with 2% oxygen. The Twist1 binding region in the GCM1 gene was detected by chromatin-immunoprecipitation. RESULTS: Twist1 was expressed in human placental tissues, and the expression of Twist1 and GCM1 increased in a time-dependent manner during spontaneous syncytialization of primary CTBs and forskolin-induced fusion of BeWo cells. A reduction in Twist1 and GCM1 expression was observed under hypoxic conditions and was accompanied by inhibition of trophoblast syncytialization. Moreover, siRNA-mediated silencing of Twist1 resulted in inhibition of BeWo cells fusion and down-regulation of GCM1 expression. Furthermore, Twist1 was found to bind to the E-box-enriched region in intron 2 of the GCM1 gene during forskolin-induced fusion of BeWo cells. DISCUSSION: The above results suggest that Twist1 is required during trophoblast syncytialization. Twist1 may promote trophoblast syncytialization by regulating the expression of GCM1. PMID- 26992675 TI - Placental function assessed visually using half-Fourier acquisition single-shot turbo spin-echo (HASTE) magnetic resonance imaging. AB - INTRODUCTION: To investigate a simple visual assessment method of placental function using half-Fourier acquisition single-shot turbo spin-echo (HASTE) magnetic resonance imaging (MRI). METHODS: The institutional review board approved this retrospective study of fetal MRI in 48 singleton pregnant women for whom placentas had undergone clinical pathological examinations. Two readers independently assessed the placentas using the HASTE scoring system, particularly emphasizing the visualization of the regular two-tone pattern inside and signal intensity (SI) of placental parenchyma referring to SI of the fetal kidney and liver. After categorization using the HASTE scoring system, the associations between the scores and the presence of pathologically proven placental insufficiency or of low birth weight less than the tenth percentile were examined using chi-square tests. The associations between the HASTE scores and the MRI findings previously reported to suggest placental insufficiency, such as placental thickness and placenta to amniotic fluid SI ratio, were also examined using Student t-tests. RESULTS: The HASTE scores were associated significantly with the presence of pathologically proven placental insufficiency (P = .003 for reader 1; P = .04 reader 2) and birth weight less than the tenth percentile (P = .005 for reader 1; P = .003 for reader 2). The HASTE scores were associated significantly with the placenta thickness (P < .0001 for both readers) and the placenta to the amniotic fluid SI ratio (P < .0001 for both readers). DISCUSSION: The HASTE scoring system is feasible for use in clinical assessment of placental function and for diagnosing placental insufficiency. PMID- 26992677 TI - Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors. AB - INTRODUCTION: Insulin receptor (IR) and type 1 and type 2 insulin-like growth factor receptors (IGF1R and IGF2R) play important roles in regulation of placental and foetal growth. All three receptors are abundantly glycosylated. N glycosylation significantly affects protein conformation and may alter its function. We have recently found that the N-glycome of placental membrane proteins alters during gestation. The aim of the study presented herein was to investigate whether there were gestation-related changes in N-glycan profiles of placental IR and IGFRs. METHODS: Placentas from healthy women at first (FTP) and third trimester (TTP) of pregnancy were collected, membrane proteins isolated, solubilised and used as the source of IR and IGFRs. Reactivity of glycoforms of IR and IGFRs with lectins was monitored by measuring radioactivity of (125)I ligands-receptors complexes. RESULTS: Significant differences in the binding pattern of all three receptors to the lectins were observed between FTP and TTP, which suggest gestational changes in N-glycans bound to receptors. These changes include decrease in total fucosylated, core-fucosylated biantennary N-glycan (NA2F) and alpha2,6-sialo-N-glycans (for IR); decrease in total fucosylated and alpha2,6-sialo-N-glycans and an increase in NA2F N-glycans (for IGF1R) and an increase in the total fucosylation and NA2F N-glycans (for IGF2R). DISCUSSION: The gestational alterations in N-glycans attached to IR and IGFRs may represent a mechanism by which these receptors acquire new/additional roles as gestation progresses. PMID- 26992676 TI - Correlation of preterm infant illness severity with placental histology. AB - INTRODUCTION: A major goal of neonatal medicine is to identify neonates at highest risk for morbidity and mortality. Previously, we developed PhysiScore (Saria et al., 2010), a novel tool for preterm morbidity risk prediction. We now further define links between overall individual morbidity risk, specific neonatal morbidities, and placental pathologies. METHODS: 102 placentas, including 38 from multiple gestations, were available from the previously defined PhysiScore cohort (gestational age <= 34 weeks and birth weight <= 2000 g). Placentas were analyzed for gross and histologic variables including maternal malperfusion, amniotic fluid infection sequence, chronic inflammation, and fetal vascular obstruction. Risk as determined by PhysiScore and recorded neonatal morbidities were tested for statistical association with placental findings. RESULTS: In pair-wise correlations, respiratory distress syndrome, bronchopulmonary dysplasia, acute hemodynamic instability, post-hemorrhagic hydrocephalus, culture-positive sepsis, and necrotizing enterocolitis each significantly correlated with at least one placenta histology variable. Amniotic fluid infection sequence (p = 0.039), specifically the fetal inflammatory response (p = 0.017), correlated with higher PhysiScores (greater morbidity) but was not independent of gestational age and birth weight. In multivariate analyses correlating variables with all nine morbidities, gestational age (p < 0.001), placental size <10th percentile (p = 0.031), full thickness perivillous fibrin deposition (p = 0.001), and amniotic fluid infection sequence (umbilical arteritis, p = 0.031; >=2 chorionic plate vessels with vasculitis, p = 0.0125), each were significant associations. DISCUSSION: Amniotic fluid infection sequence plays a significant role in neonatal morbidity. Less neonatal morbidity was observed in older and heavier infants and those with small placental size and full thickness perivillous fibrin deposition. The combined assessment of placental gross and histologic findings together with physiologic risk evaluation may allow more precise prediction of neonatal morbidity risk soon after delivery. PMID- 26992679 TI - Differences in permeability of preterm and term fetal membranes to calcium ions - Preliminary report. AB - The metabolic activity of amniochorion contributes to the control of activation of labor-type uterine contractions. The study presents an experimental model of transport of calcium ions across the human amniochorion sampled directly after cesarean section in patients delivering both at term and prematurely. Transmembrane transport of calcium ions was lower in preterm vs. term tissue samples. The differences in permeability were most pronounced in the first 60 min of experiments. The results of the study provide evidence for the existence of an active mechanism of calcium transport which can contribute to regulating the contractility of the uterus. PMID- 26992678 TI - Nicotine inhibits LPS-induced cytokine production and leukocyte infiltration in rat placenta. AB - INTRODUCTION: Previous work conducted by our group has shown that nicotine reduces lipopolysaccharide (LPS)-induced systemic inflammatory responses and protects fetuses in pregnant Sprague-Dawley (SD) rats. In the present study, we aim to evaluate the influence of nicotine on rat placenta, including cytokine release, leukocyte infiltration, and alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) expression. METHODS: Placental tissues of SD rats on gestation day 14 (GD14) were obtained and cultured in the presence or absence of LPS and/or nicotine. Culture media after 24 h were analyzed for cytokines release using Luminex. Other pregnant SD rats were first pretreated with nicotine on GD14 and GD15, followed by LPS injection on GD16. Placentas were collected on GD18 for H&E staining to evaluate leukocyte density and for real-time PCR and western blotting to identify the alpha7-nAChR expression in different groups. RESULTS: Nicotine suppresses LPS-stimulated placental proinflammatory cytokines (IL-1, IL-2, IL-6, TNF-alpha, IFN-gamma) production except IL-17 in vitro, and reduces leucocytes infiltration in the placental chorionic plate caused by LPS in vivo. Moreover, LPS increases the alpha7-nAChR protein expression in placentas while pretreatment of nicotine inhibits it. DISCUSSION: These data show that nicotine suppresses LPS induced placental inflammation by inhibition of cytokine release and infiltration of leukocytes into the placenta, and regulates the increased expression of alpha7 nAChR in placenta after LPS treatment. Nicotine and other nicotinic agonists may be an alternative therapeutic strategy for placental inflammation. PMID- 26992680 TI - Magnesium deficiency during pregnancy in mice impairs placental size and function. AB - OBJECTIVE: Maternal magnesium (Mg) deficiency has been associated with fetal growth restriction. Using a mouse model of maternal Mg deficiency-induced fetal growth restriction, we sought to investigate the effect of Mg deficiency on placental physiology and function. METHODS: In vivo: Pregnant Swiss Webster mice were fed either 100% of the recommended amount of Mg (control) or 10%Mg (Mg deficient) (8 per group). Dams were euthanized on gestational day 17 and placentas were collected, weighed and assessed for Mg concentrations, as well as nutrient transporter mRNA expression. For nutrient transfer studies, control and Mg-deficient dams (6 per group) were injected with (14)C-amino acids and (3)H glucose and trans-placental passage was determined. In vitro: BeWo placental cells were grown in media containing 10%Mg to 100%Mg and the effects of Mg status on cell proliferation, oxidative stress and nutrient uptake were measured. Data were analyzed by Student's t-tests comparing controls vs. Mg-deficient animals or cells. For multiple comparisons, data were analyzed by ANOVA followed by Dunnett's post hoc testing. RESULTS: In vivo: Maternal Mg deficiency decreased placental Mg content, placental and fetal weights, ratio of fetal:placental weight (P < 0.05), placental Slc7a5 transporter mRNA expression and transplacental nutrient transport (P < 0.05). In vitro: Mg deficiency reduced BeWo nutrient uptake (P < 0.01) and cell proliferation (P < 0.01), and increased oxidative stress (P < 0.01). CONCLUSION: These findings highlight the adverse effects of maternal Mg deficiency on fetal weight and placental function, including transport and proliferation and may explain the fetal growth restriction observed with moderate Mg deficiency in mice. PMID- 26992681 TI - Increased expression of fatty acid binding protein 4 in preeclamptic Placenta and its relevance to preeclampsia. AB - The aim of this investigation was to determine the expression of fatty acid binding protein 4 (FABP4) in the placenta from women with preeclampsia and normal pregnancy, and to delineate the regulatory effects on thophoblast cell by FABP4. We determined the expression of FABP4 by real-time polymerase chain reaction (PCR) for messenger ribonucleic acid (mRNA) or enzyme-linked immunesorbent assay (ELISA) and Western blotting for protein. Small interference of ribonucleic acid (siRNA) and specific FABP4 inhibitor were used to inhibit FABP4. The proliferation, migration and invasion of trophoblastic cells (Swan-71 and Jar) were evaluated with cell counting kit-8, wound-healing test and transwell analysis respectively. We found the expression of FABP4 was significantly higher in the placenta of preeclamptic women than that of women with normal pregnancy (t = 4.244, P < 0.001 for mRNA; t = 4.536, P < 0.001 for protein). FABP4 siRNA significantly reduced the proliferation of trophoblasts (P < 0.001). The specific inhibition of FABP4 inhibited the proliferation of trophoblasts in a dose dependent manner (P < 0.001) and the inhibitory effect increased as the concentration of inhibitor increased. FABP4 siRNA and specific inhibitor significantly decreased the migration (P < 0.001) and invasion (P < 0.001) of trophoblasts. We concluded the increase in placental FABP4 expression in preeclampsia may affect the function of trophoblast, and this increase may have a role in the pathogenesis of preeclampsia. PMID- 26992682 TI - MiR 20a,-20b and -200c are involved in hydrogen sulfide stimulation of VEGF production in human placental trophoblasts. AB - Hydrogen sulfide (H2S) has been implicated to angiogenesis in various tissues. We sought to investigate the role of hydrogen sulfide (H2S) in regulating production of vascular endothelial growth factor (VEGF) proteins, the key factors of angiogenesis and vasculogenesis, in placenta. METHODS: Placental tissues were obtained from pregnant women with preeclampsia and healthy pregnant women who underwent elective cesarean section. Explants and trophoblasts were isolated from healthy placentas and treated with H2S donor and precursor. Western blotting was used to determine the levels of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). The levels of VEGF mRNA, miR miR-200c,-20a and 20b were determined by quantitative real time PCR. RESULTS: NaHS and l-cysteine increased VEGF but not placenta growth factor (PlGF) production in cultured explants and trophoblasts. Transfection of CBS and CSE siRNA reversed the stimulatory effect of l-cysteine on VEGF production in placental cells. H2S prolonged the half-life of VEGF mRNA and decreased the expression of miR-200c, 20a and -20b in placental cells. MiR-200c mimic and inhibitor affected VEGF mRNA and protein level, whereas miR-20a or -20b mimic and inhibitor affect VEGF protein release but not mRNA expression. The expression level of miR-200c,-20a and -20b as well as the level of CBS, CSE and VEGF were downregulated in preeclamptic placentas. CONCLUSION: H2S produced via CSE and CBS plays a critical role in VEGF production in human placenta. Reduced expression of CSE and CBS may contribute to the abnormal production of angiogenic factors in preeclamptic placenta. PMID- 26992683 TI - Sensitivity to the thromboxane A2 analog U46619 varies with inner diameter in human stem villous arteries. AB - INTRODUCTION: The vascular resistance of stem villous arteries is determined by the balance between different contractile and relaxant agents and in the utero placental circulation. Thromboxane A2 (TxA2), prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1) are considered to be among the most important contractile factors. However, it is not known if their contractile effects are consistent along the villous tree. We hypothesized that the sensitivity to different agonists could be influenced by artery diameter and thus that their contribution to placental vascular resistance may differ. METHODS: Using an isometric wire myograph, the contractility and sensitivity (pD2) to the thromboxane A2 mimetic U46619, PGF2alpha and ET-1 were investigated in isolated human stem villous arteries and human uterine fundus and isthmus arteries obtained from healthy, pregnant women who had experienced uncomplicated pregnancy. RESULTS: In fetal arteries, the pD2 values for U46619 correlated positively with arterial diameter with no such dependence observed for ET-1 and PGF2alpha. In maternal arteries, pD2 remained constant for all the agonists tested despite highly variable vessel diameter. DISCUSSION: A selective decrease in sensitivity to TxA2 receptor stimulation was observed with decreasing vascular diameter in human stem villous arteries. The contractile factors PGF2alpha and ET-1 show no such relationship. PMID- 26992684 TI - Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles. AB - INTRODUCTION: Up to 20% of hydatidiform moles are followed by malignant transformation in gestational trophoblastic neoplasia and require chemotherapy. Syncytin-1 is involved in human placental morphogenesis and is also expressed in various cancers. We assessed the predictive value of the expression of Syncytin-1 and its interactants in the malignant transformation process of hydatidiform moles. METHODS: Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR. RESULTS: Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia. CONCLUSIONS: Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context. PMID- 26992685 TI - In utero perfluorooctane sulfonate exposure causes low body weights of fetal rats: A mechanism study. AB - OBJECTIVES: The objective of the present study is to investigate the mechanism of perfluorooctane sulfonate-induced low body weight of fetus by analysis of glucocorticoid metabolizing enzyme 11beta-hydroxysteroid dehydrogenase 2 and gene expression profiling of the placenta after in utero PFOS exposure. STUDY DESIGN: Pregnant Sprague-Dawley dams were gavaged with 0, 5, and 20 mg/kg body weight PFOS daily from gestational day 12-18. On gestational day 18, pregnant dams were euthanized, placentas, and fetuses were collected. MAIN OUTCOME MEASURES: Body weights of fetuses and placentas were measured, the corticosterone levels in fetal serum, and 11beta-hydroxysteroid dehydrogenase 2 as well as the placental gene profiling were analyzed. RESULTS: 20 mg/kg PFOS significantly reduced fetal body weight and placental weight. Both 5 and 20 mg/kg PFOS increased fetal serum corticosterone levels. PFOS potently inhibited placental 11beta-hydroxysteroid dehydrogenase 2 activity. Of 21,910 genes, 45 genes were significantly downregulated >=2 fold by 20 mg/kg PFOS, including extracellular matrix (Slpi and Pi16), growth factors and hormones (Trh and Pdf), ion transporters (Aqp1, S100a4, and Abp1), signal transducers (Kap and Ampd3), and structural constituents (A2m and Des). CONCLUSIONS: PFOS exposure may alter placental development and function, causing intrauterine growth restriction via inhibiting placental 11beta hydroxysteroid dehydrogenase 2. PMID- 26992686 TI - Establishment and characterization of fetal and maternal mesenchymal stem/stromal cell lines from the human term placenta. AB - INTRODUCTION: Human placental mesenchymal stem/stromal cells (MSC) are an attractive source of MSC with great therapeutic potential. However, primary MSC are difficult to study in vitro due to their limited lifespan and patient-to patient variation. METHODS: Fetal and maternal MSC were prepared from cells of the chorionic and basal plates of the placenta, respectively. Fetal and maternal MSC were transduced with the human telomerase reverse transcriptase (hTERT). Conventional stem cell assays assessed the MSC characteristics of the cell lines. Functional assays for cell proliferation, cell migration and ability to form colonies in soft agar were used to assess the whether transduced cells retained properties of primary MSC. RESULTS: Fetal chorionic and maternal MSC were successfully transduced with hTERT to create the cell lines CMSC29 and DMSC23 respectively. The lifespans of CMSC29 and DMSC23 were extended in cell culture. Both cell lines retained important MSC characteristics including cell surface marker expression and multipotent differentiation potential. Neither of the cell lines was tumourigenic in vitro. Gene expression differences were observed between CMSC29 and DMSC23 cells and their corresponding parent, primary MSC. Both cell lines show similar migration potential to their corresponding primary, parent MSC. DISCUSSION: The data show that transduced MSC retained important functional properties of the primary MSC. There were gene expression and functional differences between cell lines CMSC29 and DMSC23 that reflect their different tissue microenvironments of the parent, primary MSC. CMSC29 and DMSC23 cell lines could be useful tools for optimisation and functional studies of MSC. PMID- 26992687 TI - Ly49 knockdown in mice results in aberrant uterine crypt formation and impaired blastocyst implantation. AB - Genetic knockdown (KD) of the mouse Ly49 receptor family is reported to result in infertility despite the presence of zona-enclosed blastocysts in the uterus. Ly49 receptors regulate leukocyte functions particularly Natural Killer (NK) cell functions and are analogous to human killer immunoglobulin-like receptors (KIRs). Histological analyses of gd3.5-4.5 B6.Ly49(KD) uteri identified hatched but retarded blastocysts with pyknotic nuclei, aberrant endometrial crypt formation and impaired uterine lumen closure accompanied by a lack of primary decidualization These data support peri-implantation roles for leukocytes expressing the Ly49 receptor repertoire and may give insight into KIR-based regulation of human infertility. PMID- 26992689 TI - Association of chorangiomas to hypoxia-related placental changes in singleton and multiple pregnancy placentas. AB - INTRODUCTION: Chorangiomas (CAs) are the most frequent non-trophoblastic tumor like-lesions of the placenta, and since they occur with an unusual frequency in pregnancies at high altitude, they are considered as a part of a spectrum of hypoxia-related vascular lesions of the placenta. The aim of our study is to describe the morphological features of the CAs and to show associations between CAs and other hypoxia related morphological changes in placentas of singleton and multiple pregnancies. MATERIALS AND METHODS: Placentas from singleton (121 vs 242) and multiple (49 vs 98) pregnancies, with and without CAs, respectively, were selected from a cohort of 15,742 placentas and enrolled into a case control study. RESULTS: Singleton placentas with CAs showed increased incidence of hypoxia-related placental changes including accelerated maturation of chorionic villi (OR = 2.40, p < 0.001), infarction (OR = 2.89, p < 0.001), decidual arteriopathy (OR = 3.24, p < 0.001), fetal thrombosis (OR = 4.05, p < 0.001) and hypercoiled umbilical cords (OR = 5.55, p < 0.001). The incidence of CAs in multiple placentas was higher in our studied cohort and a significant associated change was shown with fetal thrombosis (OR = 4.58, p = 0.017). There were no significant morphological changes between CAs in singleton compared to multiple pregnancies. DISCUSSION: In singleton placentas, CA is associated with several placental changes related to hypoxia, whereas in multiple pregnancies this relationship is not present. We speculate that CAs in multiple pregnancies might reflect an adaptive mechanism for relative hypoxia per se in these pregnancies. CONCLUSION: Our study provides evidence that CAs are associated with an increased rate of hypoxia related changes in singleton placentas. PMID- 26992688 TI - R1 changes in the human placenta at 3 T in response to a maternal oxygen challenge protocol. AB - Oxygen-enhanced MRI non-invasively monitors placental oxygenation in-vivo. This technique has been demonstrated at 1.5 Tesla (T) in healthy pregnancies. The aim of this study was to investigate whether findings are comparable at 3T. Nine pregnant volunteers underwent MRI at 3T. Scans obtained R1 (1/T1) measures from T1 maps under air, followed by a dynamic series breathing 100% oxygen. A statistically significant negative correlation was found between dR1 and gestation (P = 0.0008, r = -0.90, Pearson correlation test). The effect of the field strength was not significant within regression analysis. Placental Oxygen Enhanced MRI at 3T gives comparable results to those previously obtained at 1.5T. PMID- 26992690 TI - Pursuing equity in cancer care: implementation, challenges and preliminary findings of a public cancer referral center in rural Rwanda. AB - BACKGROUND: Cancer services are inaccessible in many low-income countries, and few published examples describe oncology programs within the public sector. In 2011, the Rwanda Ministry of Health (RMOH) established Butaro Cancer Center of Excellence (BCCOE) to expand cancer services nationally. In hopes of informing cancer care delivery in similar settings, we describe program-level experience implementing BCCOE, patient characteristics, and challenges encountered. METHODS: Butaro Cancer Center of Excellence was founded on diverse partnerships that emphasize capacity building. Services available include pathology-based diagnosis, basic imaging, chemotherapy, surgery, referral for radiotherapy, palliative care and socioeconomic access supports. Retrospective review of electronic medical records (EMR) of patients enrolled between July 1, 2012 and June 30, 2014 was conducted, supplemented by manual review of paper charts and programmatic records. RESULTS: In the program's first 2 years, 2326 patients presented for cancer-related care. Of these, 70.5% were female, 4.3% children, and 74.3% on public health insurance. In the first year, 66.3% (n = 1144) were diagnosed with cancer. Leading adult diagnoses were breast, cervical, and skin cancer. Among children, nephroblastoma, acute lymphoblastic leukemia, and Hodgkin lymphoma were predominant. As of June 30, 2013, 95 cancer patients had died. Challenges encountered include documentation gaps and staff shortages. CONCLUSION: Butaro Cancer Center of Excellence demonstrates that complex cancer care can be delivered in the most resource-constrained settings, accessible to vulnerable patients. Key attributes that have made BCCOE possible are: meaningful North-south partnerships, innovative task- and infrastructure-shifting, RMOH leadership, and an equity-driven agenda. Going forward, we will apply our experiences and lessons learned to further strengthen BCCOE, and employ the developed EMR system as a valuable platform to assess long-term clinical outcomes and improve care. PMID- 26992691 TI - Confirmation of a non-synonymous SNP in PNPLA8 as a candidate causal mutation for Weaver syndrome in Brown Swiss cattle. AB - BACKGROUND: Bovine progressive degenerative myeloencephalopathy (Weaver syndrome) is a neurodegenerative disorder in Brown Swiss cattle that is characterized by progressive hind leg weakness and ataxia, while sensorium and spinal reflexes remain unaffected. Although the causal mutation has not been identified yet, an indirect genetic test based on six microsatellite markers and consequent exclusion of Weaver carriers from breeding have led to the complete absence of new cases for over two decades. Evaluation of disease status by imputation of 41 diagnostic single nucleotide polymorphisms (SNPs) and a common haplotype published in 2013 identified several suspected carriers in the current breeding population, which suggests a higher frequency of the Weaver allele than anticipated. In order to prevent the reemergence of the disease, this study aimed at mapping the gene that underlies Weaver syndrome and thus at providing the basis for direct genetic testing and monitoring of today's Braunvieh/Brown Swiss herds. RESULTS: Combined linkage/linkage disequilibrium mapping on Bos taurus chromosome (BTA) 4 based on Illumina Bovine SNP50 genotypes of 43 Weaver affected, 31 Weaver carrier and 86 Weaver-free animals resulted in a maximum likelihood ratio test statistic value at position 49,812,384 bp. The confidence interval (0.853 Mb) determined by the 2-LOD drop-off method was contained within a 1.72-Mb segment of extended homozygosity. Exploitation of whole-genome sequence data from two official Weaver carriers and 1145 other bulls that were sequenced in Run4 of the 1000 bull genomes project showed that only a non-synonymous SNP (rs800397662) within the PNPLA8 gene at position 49,878,773 bp was concordant with the Weaver carrier status. Targeted SNP genotyping confirmed this SNP as a candidate causal mutation for Weaver syndrome. Genotyping for the candidate causal mutation in a random sample of 2334 current Braunvieh animals suggested a frequency of the Weaver allele of 0.26 %. CONCLUSIONS: Through combined use of exhaustive sequencing data and SNP genotyping results, we were able to provide evidence that supports the non-synonymous mutation at position 49,878,773 bp as the most likely causal mutation for Weaver syndrome. Further studies are needed to uncover the exact mechanisms that underlie this syndrome. PMID- 26992692 TI - Flow cytometry remission by Ig light chains ratio is a powerful marker of outcome in multiple myeloma after tandem autologous transplant: a real-life study. AB - BACKGROUND: The achievement of complete response (CR) significantly correlates with a better clinical outcome in multiple myeloma (MM) patients treated with autologous stem cell transplant (ASCT). The depth of response is one of the most relevant factors to predict patient's outcome, however the definition of CR through standard criteria has shown several limitations. METHODS: In this study we evaluated the minimal residual disease (MRD) in 50 consecutive MM patients who underwent an up-front tandem ASCT in our center, using a single-tube six-colors flow cytometry assay (FC) based on intra-cytoplasmic immunoglobulin (cy-Ig) light chains ratio evaluated on patient-specific plasma cells (PC) immune profile, in a real-life setting. RESULTS: With a sensitivity up to 10(-5), clonal-PC were documented by FC in 36.4% (12/33) of patients in conventional CR after second transplant. The number of flow MRD-negative patients significantly increased after induction and first ASCT, but not between first and second transplant. The 5-years progression-free survival (5ys-PFS) of flow MRD-negative patients after second transplant was significantly better than patients who remained MRD positive considering both all patients (5ys-PFS: 70% vs 5%) and patients in CR according to standard criteria (5ys-PFS: 67% vs 0%). CONCLUSIONS: FC remission through cy-Ig light ratio on PC sub-populations is a sensitive, highly informative, low-cost and routinely applicable MRD assay, a powerful tool in treatment response evaluation and a crucial marker of outcome in MM. PMID- 26992693 TI - Biological factors that place women at risk for HIV: evidence from a large-scale clinical trial in Durban. AB - BACKGROUND: It is well documented that the mucosal linings of the female genital tract (FGT) usually provides a robust barrier that protects against sexually acquired infections. However, to the best of our knowledge there are limited South African studies that have investigated the association between damage to the mucosal linings and the acquisition of HIV infections. We hypothesize that in this cohort of women, a higher rate of HIV seroconversions will be observed for women who present with evidence of mucosal damage. METHODS: We undertook a secondary analysis of the Methods for Improving Reproductive Health in Africa (MIRA) trial that assessed the effectiveness of the latex diaphragm and lubricant gel on HIV prevention among women. Participants underwent a physical examination which included a pelvic examination to detect the presence of mucosal abnormalities. During the physical examinations, the study clinicians examined the genitalia, cervix and vagina for signs of epithelial disruptions and abnormal vaginal discharge. The association between the various genital factors and HIV seroconversion was modeled using Cox proportional hazards regression analysis. RESULTS: In this cohort of 1485 women that had enrolled to participate in the study, women that had presented with genital epithelial disruptions and abnormal vaginal discharge were shown to be at highest risk for HIV acquisition (Hazard Ratio (HR): 4.30, 95% CI: 2.25, 8.22, p <0001, HR: 2.37, 95% CI: 1.69, 3.33, p <0.001) respectively. In addition, the Kaplan Meier analysis showed that the highest number of seroconversions was observed in women that had disrupted genital epithelia (27 per 100/py, 95% CI: 15.0, 50.7) and abnormal vaginal discharge (12 per 100/py, 95% CI: 9.70, 16.7). Other significant factors included: genital signs and symptoms (HR: 1.67, 95% CI: 1.07, 2.61, p = 0.02) and genital ulcers/sores (HR: 1.79, 95% CI: 1.05, 3.06, p = 0.03). CONCLUSION: We have shown that damage to the mucosal epithelial lining increases a women's risk of HIV seroconversion. Future studies that provide an in depth understanding of the mechanisms associated with the FGT and mucosal immunity will be most valuable. An understanding of all of these mechanisms will be key in directing the advancement of products most suitable for combating HIV infection in women. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov,number NCT00121459 on the 28th February 2007. PMID- 26992694 TI - A cellulose binding domain protein restores female fertility when expressed in transgenic Bintje potato. AB - BACKGROUND: Expression of a gene encoding the family 1 cellulose binding domain protein CBD1, identified in the cellulosic cell wall of the potato late blight pathogen Phytophthora infestans, was tested in transgenic potato to determine if it had an influence on plant cell walls and resistance to late blight. RESULTS: Multiple regenerants of potato (cv. Bintje) were developed and selected for high expression of CBD 1 transcripts. Tests with detached leaflets showed no evidence of increased or decreased resistance to P. infestans, in comparison with the blight susceptible Bintje controls, however, changes in plant morphology were evident in CBD 1 transgenics. Plant height increases were evident, and most importantly, the ability to produce seed berries from a previously sterile cultivar. Immunolocalization of CBD 1 in seed berries revealed the presence throughout the tissue. While Bintje control plants are male and female sterile, CBD 1 transgenics were female fertile. Crosses made using pollen from the late blight resistant Sarpo Mira and transgenic CBD1 Bintje as the female parent demonstrated the ability to introgress P. infestans targeted resistance genes, as well as genes responsible for color and tuber shape, into Bintje germplasm. CONCLUSIONS: A family 1 cellulose-binding domain (CBD 1) encoding gene from the potato late blight pathogen P. infestans was used to develop transgenic Bintje potato plants. Transgenic plants became female fertile, allowing for a previously sterile cultivar to be used in breeding improvement. Selection for the absence of the CBD transgene in progeny should allow for immediate use of a genetically enhanced material. Potential for use in other Solanaceous crops is proposed. PMID- 26992697 TI - Dysregulation of TrkB phosphorylation and proBDNF protein in adenylyl cyclase 1 and 8 knockout mice in a model of fetal alcohol spectrum disorder. AB - Brain-derived neurotrophic factor (BDNF) mediates neuron growth and is regulated by adenylyl cyclases (ACs). Mice lacking AC1/8 (DKO) have a basal reduction in the dendritic complexity of medium spiny neurons in the caudate putamen and demonstrate increased neurotoxicity in the striatum following acute neonatal ethanol exposure compared to wild type (WT) controls, suggesting a compromise in BDNF regulation under varying conditions. Although neonatal ethanol exposure can negatively impact BDNF expression, little is known about the effect on BDNF receptor activation and its downstream signaling, including Akt activation, an established neuroprotective pathway. Therefore, here we determined the effects of AC1/8 deletion and neonatal ethanol administration on BDNF and proBDNF protein expression, and activation of tropomyosin-related kinase B (TrkB), Akt, ERK1/2, and PLCgamma. WT and DKO mice were treated with a single dose of 2.5 g/kg ethanol or saline at postnatal days 5-7 to model late-gestational alcohol exposure. Striatal and cortical tissues were analyzed using a BDNF enzyme-linked immunosorbent assay or immunoblotting for proBDNF, phosphorylated and total TrkB, Akt, ERK1/2, and PLCgamma1. Neither postnatal ethanol exposure nor AC1/8 deletion affected total BDNF protein expression at any time point in either region examined. Neonatal ethanol increased the expression of proBDNF protein in the striatum of WT mice 6, 24, and 48 h after exposure, with DKO mice demonstrating a reduction in proBDNF expression 6 h after exposure. Six and 24 h after ethanol administration, phosphorylation of full-length TrkB in the striatum was significantly reduced in WT mice, but was significantly increased in DKO mice only at 24 h. Interestingly, 48 h after ethanol, both WT and DKO mice demonstrated a reduction in phosphorylated full-length TrkB. In addition, Akt and PLCgamma1 phosphorylation was also decreased in ethanol-treated DKO mice 48 h after injection. These data demonstrate dysregulation of a potential survival pathway in the AC1/8 knockout mice following early-life ethanol exposure. PMID- 26992698 TI - A DNA element in the slo gene modulates ethanol tolerance. AB - In Drosophila, the slo gene encodes BK-type Ca(2+)-activated K(+) channels and is involved in producing rapid functional tolerance to sedation with ethanol. Drosophila are ideal for the study of functional ethanol tolerance because the adult does not acquire metabolic ethanol tolerance (Scholz, Ramond, Singh, & Heberlein, 2000). It has been shown that mutations in slo block the capacity to acquire tolerance, that sedation with ethanol vapor induces slo gene expression in the nervous system, and that transgenic induction of slo can phenocopy tolerance (Cowmeadow, Krishnan, & Atkinson, 2005; Cowmeadow et al., 2006). Here we use ethanol-induced histone acetylation to map a DNA regulatory element in the slo transcriptional control region and functionally test the element for a role in producing ethanol tolerance. Histone acetylation is commonly associated with activating transcription factors. We used the chromatin immunoprecipitation assay to map histone acetylation changes following ethanol sedation to identify an ethanol-responsive DNA element. Ethanol sedation induced an increase in histone acetylation over a 60 n DNA element called 6b, which is situated between the two ethanol-responsive neural promoters of the slo gene. Removal of the 6b element from the endogenous slo gene affected the production of functional ethanol tolerance as assayed in an ethanol-vapor recovery from sedation assay. Removal of element 6b extended the period of functional ethanol tolerance from ~10 days to more than 21 days after a single ethanol-vapor sedation. This study demonstrates that mapping the position of ethanol-induced histone acetylation is an effective way to identify DNA regulatory elements that help to mediate the response of a gene to ethanol. Using this approach, we identified a DNA element, which is conserved among Drosophila species, and which is important for producing a behaviorally relevant ethanol response. PMID- 26992696 TI - Effect of different stressors on voluntary ethanol intake in ethanol-dependent and nondependent C57BL/6J mice. AB - Several animal models have evaluated the effect of stress on voluntary ethanol intake with mixed results. The experiments reported here examined the effects of different stressors on voluntary ethanol consumption in dependent and nondependent adult male C57BL/6J mice. In Experiment 1, restraint, forced swim, and social defeat stress procedures all tended to reduce ethanol intake in nondependent mice regardless of whether the stress experience occurred 1 h or 4 h prior to ethanol access. The reduction in ethanol consumption was most robust following restraint stress. Experiment 2 examined the effects of forced swim stress and social defeat stress on drinking in a dependence model that involved repeated cycles of chronic intermittent ethanol (CIE) exposure. Repeated exposure to forced swim stress prior to intervening test drinking periods that followed repeated cycles of CIE exposure further increased ethanol consumption in CIE exposed mice while not altering intake in nondependent mice. In contrast, repeated exposure to the social defeat stressor in a similar manner reduced ethanol consumption in CIE-exposed mice while not altering drinking in nondependent mice. Results from Experiment 3 confirmed this selective effect of forced swim stress increasing ethanol consumption in mice with a history of CIE exposure, and also demonstrated that enhanced drinking is only observed when the forced swim stressor is administered during each test drinking week, but not if it is applied only during the final test week. Collectively, these studies point to a unique interaction between repeated stress experience and CIE exposure, and also suggest that such an effect depends on the nature of the stressor. Future studies will need to further explore the generalizability of these results, as well as mechanisms underlying the ability of forced swim stress to selectively further enhance ethanol consumption in dependent (CIE-exposed) mice but not alter intake in nondependent animals. PMID- 26992695 TI - The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: Insights from rodent models. AB - Fetal Alcohol Spectrum Disorders (FASD) are characterized by deficits in working memory, response inhibition, and behavioral flexibility. However, the combination and severity of impairments are highly dependent upon maternal ethanol consumption patterns, which creates a complex variety of manifestations. Rodent models have been essential in identifying behavioral endpoints of prenatal alcohol exposure (PAE). However, experimental model outcomes are extremely diverse based on level, pattern, timing, and method of ethanol exposure, as well as the behavioral domain assayed and paradigm used. Therefore, comparisons across studies are difficult and there is currently no clear comprehensive behavioral phenotype of PAE. This lack of defined cognitive and behavioral phenotype is a contributing factor to the difficulty in identifying FASD individuals. The current review aims to critically examine preclinical behavioral outcomes in the social, cognitive, and affective domains in terms of the PAE paradigm, with a special emphasis on dose, timing, and delivery, to establish a working model of behavioral impairment. In addition, this review identifies gaps in our current knowledge and proposes future areas of research that will advance knowledge in the field of PAE outcomes. Understanding the complex behavioral phenotype, which results from diverse ethanol consumption will allow for development of better diagnostic tools and more critical evaluation of potential treatments for FASD. PMID- 26992699 TI - Species differences in the effects of the kappa-opioid receptor antagonist zyklophin. AB - We have shown that dysregulation of the dynorphin/kappa-opioid receptor (DYN/KOR) system contributes to escalated alcohol self-administration in alcohol dependence and that KOR antagonists with extended durations of action selectively reduce escalated alcohol consumption in alcohol-dependent animals. As KOR antagonism has gained widespread attention as a potential therapeutic target to treat alcoholism and multiple neuropsychiatric disorders, we tested the effect of zyklophin (a short-acting KOR antagonist) on escalated alcohol self-administration in rats made alcohol-dependent using intermittent alcohol vapor exposure. Following dependence induction, zyklophin was infused centrally prior to alcohol self administration sessions and locomotor activity tests during acute withdrawal. Zyklophin did not impact alcohol self-administration or locomotor activity in either exposure condition. To investigate the neurobiological basis of this atypical effect for a KOR antagonist, we utilized a kappa-, MU-, and delta-opioid receptor agonist-stimulated GTPyS coupling assay to examine the opioid receptor specificity of zyklophin in the rat brain and mouse brain. In rats, zyklophin did not affect U50488-, DAMGO-, or DADLE-stimulated GTPyS coupling, whereas the prototypical KOR antagonist nor-binaltorphimine (norBNI) attenuated U50488 induced stimulation in the rat brain tissue at concentrations that did not impact MU- and delta-receptor function. To reconcile the discrepancy between the present rat data and published mouse data, comparable GTPyS assays were conducted using mouse brain tissue; zyklophin effects were consistent with KOR antagonism in mice. Moreover, at higher concentrations, zyklophin exhibited agonist properties in rat and mouse brains. These results identify species differences in zyklophin efficacy that, given the rising interest in the development of short-duration KOR antagonists, should provide valuable information for therapeutic development efforts. PMID- 26992701 TI - Does acute alcohol intoxication cause transaminase elevations in children and adolescents? AB - Several long-term effects of alcohol abuse in children and adolescents are well described. Alcohol abuse has severe effects on neurodevelopmental outcome, such as learning disabilities, memory deficits, and decreased cognitive performance. Additionally, chronic alcohol intake is associated with chronic liver disease. However, the effects of acute alcohol intoxication on liver function in children and adolescents are not well characterized. The aim of this study was to determine if a single event of acute alcohol intoxication has short-term effects on liver function and metabolism. All children and adolescents admitted to the Department of Pediatrics and Adolescent Medicine between 2004 and 2011 with the diagnosis "acute alcohol intoxication" were included in this retrospective analysis. Clinical records were evaluated for age, gender, alcohol consumption, blood alcohol concentration, symptoms, and therapy. Blood values of the liver parameters, CK, creatinine, LDH, AP, and the values of the blood gas analysis were analyzed. During the 8-year study period, 249 children and adolescents with the diagnosis "acute alcohol intoxication" were admitted, 132 (53%) girls and 117 (47%) boys. The mean age was 15.3 +/- 1.2 years and the mean blood alcohol concentration was 0.201 +/- 0.049%. Girls consumed significantly less alcohol than boys (64 g vs. 90 g), but reached the same blood alcohol concentration (girls: 0.199 +/- 0.049%; boys: 0.204 +/- 0.049%). The mean values of liver parameters were in normal ranges, but AST was increased in 9.1%, ALT in 3.9%, and gammaGT in 1.4%. In contrast, the mean value of AST/ALT ratio was increased and the ratio was elevated in 92.6% of all patients. Data of the present study showed significant differences in the AST/ALT ratio (p < 0.01) in comparison to a control group. Data of the present study indicate that there might be an effect of acute alcohol intoxication on transaminase levels. The AST/ALT ratio seems to reflect the damage in hepatocytes after intensive alcohol consumption. The present study indicates a sex-specific difference in alcohol metabolism and effects between girls and boys: girls need less alcohol than boys to achieve the same blood alcohol levels than boys, and are more prone to loss of consciousness. PMID- 26992700 TI - Alcohol consumption in upper aerodigestive tract cancer: Role of head and neck surgeons' recommendations. AB - This study aims to describe the prevalence of alcohol consumption in patients diagnosed with an upper aerodigestive tract cancer (UADTC) and evaluate the clinical impact of head and neck surgeons' recommendations on alcohol intake. An observational, retrospective, and cross-sectional study was conducted. Socio demographic data, type of cancer, psychiatric history, substance-use history, and DSM-IV-TR criteria for alcohol dependence were recorded. Patients were asked to report their alcohol consumption before UADTC diagnosis and during their follow up. All patients were asked if they had received from the specialist any recommendation to reduce or stop their alcohol consumption. One hundred ninety one patients were included. Laryngeal cancer was the most frequent. 85.3% of patients were alcohol consumers before being diagnosed, 39.8% were risky drinkers, and 13.1% had alcohol dependence. The prevalence of alcohol use decreased by 16.7% after the UADTC was diagnosed. The proportion of risky drinkers decreased from 46.6% to 24.5%. Almost half of the patients did not recall having received any recommendation regarding alcohol consumption. Receiving a recommendation was independently associated with a positive response (reduced or stopped alcohol consumption) with an Odds Ratio 3.7; p < 0.001. Prevalence of alcohol dependence and risky drinking (39.8%) is high in UADTC patients, compared to the general population. Otorhinolaryngologists and head and neck surgeons frequently provide recommendations about alcohol consumption, which has a relevant impact on the reduction of alcohol intake. Further prospective studies focused on brief advice should be performed in order to demonstrate effectiveness in this population. PMID- 26992702 TI - Ethanol-induced conditioned taste aversion in Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low-Preferring (WLP) rats. AB - The aversive action of the pharmacological properties of ethanol was studied in selectively bred Warsaw Alcohol High-Preferring (WHP) and Warsaw Alcohol Low Preferring (WLP) rats. For this study, a conditioned-taste aversion test was used. Male WHP and WLP rats were submitted to daily 20-min sessions for 5 days, in which a saccharin solution (1.0 g/L) was available (pre-conditioning phase). Next, this drinking was paired with the injection of ethanol (0, 0.5, 1.0 g/kg), intraperitoneally [i.p.] immediately after removal of the saccharin bottle (conditioning phase). Afterward, the choice between the saccharin solution and water was extended for 18 subsequent days for 20-min daily sessions (post conditioning phase). Both doses of ethanol did not produce an aversion to saccharin in WLP and WHP rats in the conditioning phase. However, injection of the 1.0 g/kg dose of ethanol produced an aversion in WLP rats that was detected by a decrease in saccharin intake at days 1, 3, 7, and 10 of the post conditioning phase, with a decrease in saccharin preference for 16 days of the post-conditioning phase. Conditioned taste aversion, measured as a decrease in saccharin intake and saccharin preference, was only visible in WHP rats at day 1 and day 3 of the post-conditioning phase. This difference between WLP and WHP rats was apparent despite similar blood ethanol levels in both rat lines following injection of 0.5 and 1.0 g/kg of ethanol. These results may suggest differing levels of aversion to the post-ingestional effects of ethanol between WLP and WHP rats. These differing levels of aversion may contribute to the selected line difference in ethanol preference in WHP and WLP rats. PMID- 26992703 TI - Positive linear dose-response relationships, but no J-shaped relationship, between drinking habits and estimated glomerular filtration rate in middle-aged Japanese men. AB - The relationship between drinking frequency and amount of alcohol consumption (i.e., drinking habits) and the risk of chronic kidney disease (CKD) remains unclear. We aimed to clarify either a linear or J-shaped dose-response relationship between drinking habits and estimated glomerular filtration rate (eGFR) as a biomarker for identifying individuals at high risk of CKD. In a large scale cross-sectional study, 403 men and 121 women with an eGFR of 30-60 mL/min per 1.73 m(2) were defined as cases, and 1209 men and 363 women with >=60 mL/min/1.73 m(2) were randomly extracted as controls (one case subject was matched with three control subjects, matched according to age and season of data collection). We calculated multivariate-adjusted CKD risk and the corresponding mean eGFR according to drinking habits. In men, negative and positive linear relationships with drinking habits were found for CKD risk and mean eGFR (p < 0.001 for all linear terms), respectively, but there were no corresponding J shaped relationships (not significant for all quadratic terms). In regard to the mean eGFR, however, positive linear relationships were only shown in men in the highest eGFR quartile (p < 0.05 and p < 0.01 for drinking frequency and amount of alcohol consumption, respectively). In women, no association was found. Regarding each drinking habit, we found a positive linear dose-response relationship to eGFR in middle-aged men with an eGFR >=30 mL/min/1.73 m(2). PMID- 26992704 TI - Executive performance and dysexecutive symptoms in binge drinking adolescents. AB - Alcohol is probably the most common legal drug of abuse in Western countries. The prevalence of binge drinking (BD) pattern of alcohol consumption among adolescents is a worrisome phenomenon. Adolescents and university students who practice a BD pattern have difficulty performing tasks involving prefrontal cortex functions, such as working memory, planning, attention, and decision making. The aim of the present study was to investigate the association between BD and executive functioning in adolescents. Two hundred twenty-three high-school students between 12 and 18 years old (15.19 +/- 2.13) participated in our study. They were assigned to one of three groups according to their pattern of alcohol consumption: BD (subjects who consumed alcohol intensively, n = 48), MAC (subjects who consumed alcohol moderately, n = 53), and CTR (non-drinking subjects, n = 122). The students were evaluated with two groups of testing tools: a set of performance neuropsychological tests and two questionnaires of executive functioning. The results showed that the students who drank alcohol exhibited a more pronounced dysexecutive symptomatology (disinhibition, executive dysfunction, intentionality, executive memory), but they obtained better results than controls on some of the neuropsychological tests such as Spatial Location, Five Digit Tests, or Stroop Test. According to the results, we can deduce that heavy alcohol drinking in adolescents brings a certain dysfunction of prefrontal circuits. This prefrontal dysfunction is not so clearly demonstrated in the neuropsychological tests used, but it was observed in the performance of daily activities. In the Discussion section we raise issues about sociodemographic features of the sample and ecological validity of the traditional neuropsychological tests. The neurotoxic effects of BD on prefrontal cortex can be less evident throughout adolescence, but if alcohol consumption persists, the executive dysfunction would be exacerbated. PMID- 26992705 TI - Unravelling exemestane: From biology to clinical prospects. AB - Aromatase inhibitors (AIs) are anti-tumor agents used in clinic to treat hormone dependent breast cancer. AIs block estrogens biosynthesis by inhibiting the enzyme aromatase, preventing tumor progression. Exemestane, a third-generation steroidal AI, belongs to this class of drugs and is currently used in clinic to treat postmenopausal women, due to its high efficacy and good tolerability. Here, its pharmacological and biological aspects as well as its clinical applications and comparison to other endocrine therapeutic agents, are reviewed. It is also focused the benefits and risks of exemestane, drawbacks to be overcome and aspects to be explored. PMID- 26992706 TI - Least square neural network model of the crude oil blending process. AB - In this paper, the recursive least square algorithm is designed for the big data learning of a feedforward neural network. The proposed method as the combination of the recursive least square and feedforward neural network obtains four advantages over the alone algorithms: it requires less number of regressors, it is fast, it has the learning ability, and it is more compact. Stability, convergence, boundedness of parameters, and local minimum avoidance of the proposed technique are guaranteed. The introduced strategy is applied for the modeling of the crude oil blending process. PMID- 26992707 TI - Capsule Commentary on Min et al., Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes: How to Escalate Therapy for Patients who Fail Sulfonylureas. PMID- 26992708 TI - Capsule Commentary on Luo et al., A Comparison of Health Plan- and Provider Delivered Chronic Care Management Models on Patient Clinical Outcomes. PMID- 26992709 TI - Model-based estimation of the attributable fraction for cross-sectional, case control and cohort studies using the R package AF. AB - The attributable fraction (or attributable risk) is a widely used measure that quantifies the public health impact of an exposure on an outcome. Even though the theory for AF estimation is well developed, there has been a lack of up-to-date software implementations. The aim of this article is to present a new R package for AF estimation with binary exposures. The package AF allows for confounder adjusted estimation of the AF for the three major study designs: cross-sectional, (possibly matched) case-control and cohort. The article is divided into theoretical sections and applied sections. In the theoretical sections we describe how the confounder-adjusted AF is estimated for each specific study design. These sections serve as a brief but self-consistent tutorial in AF estimation. In the applied sections we use real data examples to illustrate how the AF package is used. All datasets in these examples are publicly available and included in the AF package, so readers can easily replicate all analyses. PMID- 26992710 TI - Atypical global Takotsubo syndrome in a patient with acute disseminated encephalomyelitis. PMID- 26992711 TI - Is cardiopulmonary exercise testing essential to indicate ventricular assist device implantation in patients with INTERMACS profile 4-7? AB - Cardiopulmonary exercise testing (CPXT) is a promising tool for predicting 2-year cardiac death or ventricular assist device (VAD) implantation in patients assigned to INTERMACS profile 4-7. However, CPXT is not available in all hospitals. We evaluated 130 patients <65 years old with advanced heart failure assigned to INTERMACS profile 4-7 who underwent CPXT. CPXT scores (0-8 points), which we created recently, and the Seattle HF Model (SHFM) scores were both significant predictors of 2-year cardiac death or VAD implantation (14 events) by Cox-regression analysis (P < 0.05 for both) and had comparable areas under the curve (AUCs) in receiver operating characteristic analyses (0.811 vs. 0.737, P > 0.05). The combination score: age <46 years and serum sodium concentration <137 mEq/L, both of which were significant predictors of cardiac death or VAD implantation by uni/multivariate Cox-regression analyses, had a significantly higher AUC than did CPXT scores (0.909, P < 0.05). In a validation study, the AUC of the combination score was comparable with that of SHFM among 52 patients <65 years old receiving adaptive servo-ventilator treatment (0.753 vs. 0.794, P > 0.05). In conclusion, VAD indication may be discussed without CPXT in patients <65 years old with INTERMACS profile 4-7 at least in the current Japanese situation. PMID- 26992712 TI - [Classification of periprosthetic shoulder fractures]. AB - The key targets in the treatment of periprosthetic humeral fractures (PHF) are the preservation of bone, successful bony consolidation and provision of a stable anchoring of the prosthesis with the major goal of restoring the shoulder-arm function. A substantial problem of periprosthetic shoulder fractures is the fact that treatment is determined not only by the fracture itself but also by the implanted prosthesis and its function. Consequently, the exact preoperative shoulder function and, in the case of an implanted anatomical prosthesis, the status and function of the rotator cuff need to be assessed in order to clarify the possibility of a secondarily occurring malfunction. Of equal importance in this context is the type of implanted prosthesis. The existing classification systems of Wright and Cofield, Campbell et al., Groh et al. and Worland et al. have several drawbacks from a shoulder surgeon's point of view, such as a missing reference to the great variability of the available prostheses and the lack of an evaluation of rotator cuff function. The presented 6-stage classification for the evaluation of periprosthetic fractures of the shoulder can be considered just as simple or complex to understand as the classification of the working group for osteosynthesis problems (AO, Arbeitsgemeinschaft fur Osteosynthesefragen), depending on the viewpoint. From our point of view the classification presented here encompasses the essential points of the existing classification systems and also covers the otherwise missing points, which should be considered in the assessment of such periprosthetic fractures. The classification presented here should provide helpful assistance in the daily routine to find the most convenient form of therapy. PMID- 26992713 TI - [Periprosthetic humeral fractures: Strategies and techniques of revision arthroplasty]. AB - The primary aims when performing revision arthroplasty of periprosthetic humeral fractures (PHF) are preservation of bone stock, achieving fracture healing and preserving a stable prosthesis with the focus on regaining the preoperative shoulder-arm function. The indications for revision arthroplasty are given in PHF in combination with loosening of the stem. In addition, further factors must be independently clarified in the case of an anatomical arthroplasty. In this context secondary glenoid erosion as well as rotator cuff insufficiency are potential factors for an extended revision procedure. For the performance of revision surgery modular revision sets including long stems, revision glenoid and metaglene components as well as plate and cerclage systems are obligatory besides the explantation instrumentation. Despite a loosened prosthesis, a transhumeral removal of the stem along with a subpectoral fenestration are often required. Length as well as bracing of revision stems need to bridge the fracture by at least twice the humeral diameter. Moreover, in many cases a combined procedure using an additional distal open reduction and internal fixation (ORIF) plus cable cerclages as well as biological augmentation might be needed. Assuming an adequate preparation, the experienced surgeon is able to achieve a high fracture union rate along with an acceptable or even good shoulder function and to avoid further complications. PMID- 26992714 TI - [Osteosynthesis after periprosthetic fractures of the knee joint]. AB - Periprosthetic fractures around the knee joint are of increasing relevance due to increasing numbers of total knee replacements and increasing life expectations. These fractures can be a real challenge due to an often limited patient compliance, reduced bone quality and impaired bone perfusion of potential intramedullary shafts resulting in poor healing and lack of fixation options for screws. These fractures necessitate special knowledge and approaches, which are systematically dealt with in this article, beginning with the correct diagnostics through to the most recent developments in the field of osteosynthetic techniques. The trends of minimally invasive techniques are presented and the options and limitations are described. PMID- 26992715 TI - Maternal Intimate Partner Violence: Relationships with Language and Neurological Development of Infants and Toddlers. AB - Objectives This longitudinal study examined the influence of Intimate Partner Violence (IPV) experience of pregnant women participating in the Domestic Violence Enhanced Home Visitation Program on the language and neurological development of infants and toddlers. Methods A total of 210 infants and toddlers born to women reporting low, moderate, and high levels of IPV were included in the analysis. Logistic regression analysis was used to determine the bivariate association between maternal IPV and risk of language and neurological delay of infants and toddlers and between covariates and language and neurological delay. Generalized estimating equation models with logit link was used to predict the risk of language and neurological delay of infants and toddlers as a result of maternal IPV. Results Infants and toddlers born to women exposed to moderate levels of IPV had increased odds of language delay compared to infants and toddlers of women who experienced low levels of violence (OR 5.31, 95 % CI 2.94, 9.50, p < 0.001). Infants and toddlers born to women who experienced moderate and high levels of IPV were at higher risk of neurological delay respectively, compared to infants and toddlers of women who experienced low levels of IPV (OR 5.42, 95 % CI 2.99, 9.82, p < 0.001 and OR 2.57, 95 % CI 1.11, 5.61, p = 0.026). Conclusions for Practice Maternal IPV is associated with increased risk of language and neurological delay of infants and toddlers. These findings have implications for health care for women and infants exposed to IPV. Clinicians including pediatricians working with pregnant women should screen for IPV throughout pregnancy to identify women and children at risk. Interventions to reduce maternal IPV and early intervention services for infants and toddlers exposed to IPV are necessary for optimal maternal and child health. PMID- 26992716 TI - The secondary structure and the thermal unfolding parameters of the S-layer protein from Lactobacillus salivarius. AB - Surface layer (S-layer) proteins have been identified in the cell envelope of many organisms, such as bacteria and archaea. They self-assemble, forming monomolecular crystalline arrays. Isolated S-layer proteins are able to recrystallize into regular lattices, which proved useful in biotechnology. Here we investigate the structure and thermal unfolding of the S-layer protein isolated from Lactobacillus salivarius 16 strain of human origin. Using circular dichroism (CD) spectroscopy, and the software CDSSTR from DICHROWEB, CONTINLL from CDPro, as well as CDNN, we assess the fractions of the protein's secondary structural elements at temperatures ranging between 10 and 90 degrees C, and predict the tertiary class of the protein. To study the thermal unfolding of the protein, we analyze the temperature dependence of the CD signal in the far- and near-UV domains. Fitting the experimental data by two- and three-state models of thermal unfolding, we infer the midpoint temperatures, the temperature dependence of the changes in Gibbs free energy, enthalpy, and entropy of the unfolding transitions in standard conditions, and the temperature dependence of the equilibrium constant. We also estimate the changes in heat capacity at constant pressure in standard conditions. The results indicate that the thermal unfolding of the S-layer protein from L. salivarius is highly cooperative, since changes in the secondary and tertiary structures occur simultaneously. The thermodynamic analysis predicts a "cold" transition, at about -3 degrees C, of both the secondary and tertiary structures. Our findings may be important for the use of S layer proteins in biotechnology and in biomedical applications. PMID- 26992717 TI - Long-Term Efficacy of Tenofovir Disoproxil Fumarate Therapy in Nucleos(t)ide Experienced Chronic Hepatitis B Patients. AB - BACKGROUND AND OBJECTIVES: Tenofovir disoproxil fumarate (TDF) therapy is a therapeutic option for nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV). In this study, we evaluated the efficacy of TDF alone compared with the efficacy of TDF plus additional NA combinations in NA-experienced CHB patients. METHODS: This retrospective cohort study included 108 patients with a serum HBV DNA level above 5.0 log10 IU/ml who were treated with TDF alone (monotherapy group) or TDF combined with additional NAs (combination therapy group) for 30 months. RESULTS: At month 30, both therapies resulted in the suppression of HBV DNA levels: 66 of 66 patients (100 %) in the monotherapy group and 40 of 42 patients (95.23 %) in the combination therapy group achieved virologic suppression. Kaplan-Meier curves revealed median times for virologic suppression of 3.12 months in the monotherapy group and 5.23 months in the combination therapy group (p = 0.699). The probability of virologic suppression was comparable between treatment groups. At month 6, more patients achieved normal alanine aminotransferase (ALT) levels in the monotherapy group (p = 0.029). During the treatment period, no patients experienced severe renal dysfunction. CONCLUSION: TDF monotherapy and TDF plus additional NAs have comparable antiviral efficacy in CHB patients after NA treatment failure. PMID- 26992718 TI - Coronary Artery Bypass Grafting in Elderly Patients: Insights from a Comparative Analysis of Total Arterial and Conventional Revascularization. AB - The benefits of total arterial (TAR) versus conventional (CR) revascularization are controversial in the higher-risk cohort of elderly patients. Taking for granted its benefit on long-term survival, we evaluated the effect of TAR on safety (death, myocardial infarction, and stroke) of patients undergoing CABG. Between 2000 and 2009, 487 patients >75 years underwent isolated CABG at our institution (150 TAR and 337 CR). Patients with arterial free-grafts were excluded. After propensity matching, the outcomes of 131 TAR and 127 CR patients were compared. TAR patients had lower incidence of post-operative myocardial infarction (p = 0.025) and stroke (p = 0.005). They also experienced shorter intensive care unit (p = 0.046) and ward stay (p = 0.028), lower output of TnI (p = 0.035), and less wound complications (leg included) (p = 0.0001), while mortality was comparable (p = 0.57). In our cohort of elderly patients with multivessel disease, TAR was associated with lower rates of myocardial infarction, stroke, and shorter hospital stay. PMID- 26992719 TI - Do Stemmed Tibial Components in Total Knee Arthroplasty Improve Outcomes in Patients With Obesity? AB - BACKGROUND: Recent clinical studies have reported that patients with higher body mass index (BMI) are more likely to experience premature failure of total knee arthroplasty (TKA), lower knee scores, and perhaps more pain in the prosthetic joint. However, it is not known whether certain implant design features such as tibial stems might be associated with differences in the frequency of tibial pain in patients with higher BMIs. QUESTIONS/PURPOSES: Therefore, it was our aim to compare (1) function and pain (as measured by the New Knee Society Score, Knee Injury and Osteoarthritis Outcome Score [KOOS], and visual analog pain scores); (2) quality of life (as measured by SF-12); and (3) mechanical complications and premature revision (defined as revision before 2 years) between patients with obesity undergoing TKA (BMI > 30 kg/m2) who received either a stemmed or an unstemmed tibial component. METHODS: In this randomized controlled trial, 120 patients with a BMI > 30 kg/m2 scheduled for primary arthritis TKAs and end-stage knee osteoarthritis were included. Patients were stratified into groups defined as moderately obese (BMI 30-35 kg/m2, N = 60) and severely obese (BMI > 35 kg/m2, N = 60) groups. Patients in each stratified subgroup then were randomized to receive either a stemmed (10 mm/100 mm) proximally cemented tibial component or the other, a standard cemented component. Patients were evaluated preoperatively and 2 years after surgery using the new Knee Society Score (KSS), KOOS, SF-12 score, and a visual analog pain score after 100 meters of walking. Although no minimum clinically important differences (MCIDs) have yet been defined for the new KSS, we considered differences smaller than 10 points to be unlikely to be clinically important; the MCID for the KOOS is estimated at 8 to 10 points, the SF-12 to be 4 points, and the visual analog scale to be 2 cm on a 10-cm scale. Patients were followed until death, revision, or for a minimum of 2 years (mean, 3 +/- 0.8 years; range, 2-4 years). No patient was lost to followup before 2 years. RESULTS: Although we found that patients treated with stemmed TKAs had higher functional outcomes, the differences were small and unlikely to be clinically important (subjective KSS mean 69 +/- 7 points versus 75 +/- 7, mean difference 6 points, 95% confidence interval [CI] 2-11, p = 0.03; objective KSS mean 80 +/- 6 points versus 85 +/- 6 points, mean difference 5 points, 95% CI 0 9, p = 0.01). Compared with patients with a stemmed TKA, patients with a standard implant reported lower KOOS pain subscores (81 +/- 9 versus 76 +/- 8; p = 0.04) and lower KOOS symptom subscores (74 +/- 7 versus 68 +/- 7; p = 0.03). The proportions of patients experiencing complications were not different with the numbers available for all groups and subgroups. CONCLUSIONS: Although we detected differences in some patient-reported outcomes scores for pain and function favoring implants with stems, the differences were small and unlikely to be clinically important. Because these stems may have disadvantages, perhaps including difficulty of revision, we cannot draw a strong conclusion in support of their use. LEVEL OF EVIDENCE: Level I, therapeutic study. PMID- 26992720 TI - Erratum to: CORR Insights(r): How Do Hindfoot Fusions Affect Ankle Biomechanics: A Cadaver Model. PMID- 26992721 TI - How Does the Level of Nerve Root Resection in En Bloc Sacrectomy Influence Patient-Reported Outcomes? AB - BACKGROUND: For patients with sacral tumors, who are well enough for surgery, en bloc resection is the preferred treatment. Survival, postoperative complications, and recurrent rates have been described, but patient-reported outcomes often are not included in these studies. QUESTIONS/PURPOSES: The purposes of this study were (1) to compare patient-reported outcomes after en bloc sacrectomy, based on the level of sacral nerve root resection, in terms of mental health, physical health, bowel function, and sexual function; and (2) to assess differences in terms of mental health, physical health, and pain between patients with and without a colostomy. METHODS: A total of 74 patients, of whom 58 (78%) were diagnosed with chordoma, were surveyed between February 2012 and October 2014. This represented 48% of patients with sacral chordoma who were alive and who had been treated with a transverse sacral resection between June 2000 and August 2013 at three institutions with a minimum followup of 6 months (mean, 59 months; range, 6-255 months). We chose 6 months because we believe that neurologic deficits generally are stable by this point and that patients generally have recovered from the operation by this time. Patients were divided into five groups based on the most caudal nerve root spared: L5 (N = 10), S1 (N = 22), S2 (N = 17), S3 (N = 18), and S4 (N = 7). Only postoperative outcomes were collected using the National institute of Health's Patient Reported Measurement Information System (PROMIS) Global Health survey, PROMIS Pain Interference survey, PROMIS Pain Intensity survey, PROMIS Sexual Function survey, and the Modified Obstruction and Defecation Score survey. RESULTS: Differences between two adjacent levels were found in terms of mental health, physical health, and sexual function. Patients in whom the S2 nerve roots were spared had a lower mental health score (median = 44, interquartile range [IQR] = 41-51) than patients in whom the S3 nerve roots were spared (median = 53, IQR = 48-56, q = 0.049). Patients in whom the S2 nerve roots were spared had a slightly lower physical health score (median = 42, IQR = 40-51) than patients in whom the S3 nerve roots were spared (median = 47, IQR = 45-54, q = 0.043). Patients in whom the S1 roots were spared (median = 1.0, range = 1.0-1.0) had a lower orgasm score than patients in whom the S2 nerve roots were spared (median = 3, range = 2-5, q = 0.027). No differences in terms of mental health, physical health, or pain were found between the colostomy group and the no colostomy group. CONCLUSIONS: The combination of our findings can be used to further educate patients and discuss expectations. In an operative setting, these data can be considered when deciding to place a colostomy. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26992722 TI - Seeking new surgical predictors of mesh exposure after transvaginal mesh repair. AB - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to explore new preventable risk factors for mesh exposure. METHODS: A retrospective review of 92 consecutive patients treated with transvaginal mesh (TVM) in the urogynecological unit of our university hospital. An analysis of perioperative predictors was conducted in patients after vaginal repairs using a type 1 mesh. Mesh complications were recorded according to International Urogynecological Association (IUGA) definitions. Mesh-exposure-free durations were calculated by using the Kaplan-Meier method and compared between different closure techniques using log-rank test. Hazard ratios (HR) of predictors for mesh exposure were estimated by univariate and multivariate analyses using Cox proportional hazards regression models. RESULTS: The median surveillance interval was 24.1 months. Two late occurrences were found beyond 1 year post operation. No statistically significant correlation was observed between mesh exposure and concomitant hysterectomy. Exposure risks were significantly higher in patients with interrupted whole-layer closure in univariate analysis. In the multivariate analysis, hematoma [HR 5.42, 95 % confidence interval (CI) 1.26-23.35, P = 0.024), Prolift mesh (HR 5.52, 95 % CI 1.15-26.53, P = 0.033), and interrupted whole-layer closure (HR 7.02, 95 % CI 1.62-30.53, P = 0.009) were the strongest predictors of mesh exposure. CONCLUSION: Findings indicate the risks of mesh exposure and reoperation may be prevented by avoiding hematoma, large amount of mesh, or interrupted whole-layer closure in TVM surgeries. If these risk factors are prevented, hysterectomy may not be a relative contraindication for TVM use. We also provide evidence regarding mesh exposure and the necessity for more than 1 year of follow-up and preoperative counselling. PMID- 26992723 TI - Clinical significance of diabetes mellitus on detrusor functionality on stress urinary incontinent women without bladder outlet obstruction. AB - INTRODUCTION AND HYPOTHESIS: Our aim was to evaluate the effect of diabetes mellitus (DM) on detrusor contractility (DC) in women without bladder outlet obstruction (BOO) by using urodynamic study (UDS). METHODS: We reviewed the clinical records of 863 consecutive women without BOO, each of whom was diagnosed with stress urinary incontinence (SUI) by UDS. Uroflowmetry measurements included maximal flow rate (Qmax), time to Qmax, voided volume, and postvoid residual urine volume (PVR). Data from filling cystometry included the first strong desire to void and the Valsalva leak-point pressure (VLPP). For voiding cystometry data, detrusor pressure at Qmax (Pdet@Qmax) and bladder contractility index (BCI) were analyzed. In the DM group, the level of glycosylated hemoglobin (HbA1c) and DM duration were measured. RESULTS: After the application of exclusion criteria, complete UDS data of 708 patients were available. The cohort was divided into two groups according to DM status. The DM group comprised 92 (12.9 %) patients, the non-DM group 616 (87.0 %). Mean maximal flow rate and Pdet@Qmax and bladder contractility index were lower in the DM group, in whom mean DM duration was 9.24 +/- 7.63 years and mean HbA1c level 7.27 +/- 1.43 %. DM duration was significantly correlated with Qmax (-0.309, p = 0.003), Pdet@Qmax (-0.369, p < 0.001), and BCI (-0.409, p < 0.001). Moreover, the HbA1c level was significantly correlated with Qmax (-0.256, p = 0.016), Pdet@Qmax (-0.231, p = 0.026), and BCI (-0.308, p = 0.002). CONCLUSIONS: Our UDS data revealed that DM is associated with impaired DC in women without BOO. Moreover, longer DM duration and poor glycemic control were associated with impaired DC. PMID- 26992724 TI - Sacrocolpopexy for posthysterectomy vaginal vault prolapse: long-term follow-up. AB - INTRODUCTION AND HYPOTHESIS: Abdominal sacrocolpopexy (ASC) is considered the gold standard for vaginal vault prolapse (VVP) repair. Our aim was to evaluate the long-term durability of its anatomic and functional results. METHODS: This was a prospective series of women undergoing ASC for symptomatic VVP stage III or IV according to the Pelvic Organ Prolapse Quantification (POP-Q) system. All patients were followed up every 3 months for the first postoperative year and then annually for anatomical and functional outcomes and complications. Only patients with at least 48 months of follow-up were included in this report. Anatomic success was defined as postoperative prolapse stage 0 or I. Statistical analysis was performed using the nonparametric Mann-Whitney U test for the analysis of continuous variables and the McNemar and chi(2) test for categorical data. RESULTS: Sixty-seven women were followed up for a median of 60 months (range 48-144). Anatomical success was 100 % for apical prolapse and 94 and 91 % for anterior and posterior compartments, respectively. There were only four (6 %) and six (9 %) cases of stage II persistence or recurrence for the anterior and posterior compartments, respectively, which did not require reoperation. There was no vault prolapse recurrence. Voiding and storage urinary and sexual symptoms were significantly improved. Anorectal dysfunction symptoms persisted in 40.6 % of patients with these symptoms preoperatively and developed de novo in 22.8 % of patients without them preoperatively. Three mesh exposures were noted. Sixty three patients (94 %) were extremely or very much improved with sacrocolpopexy according to the Patient Global Impression-Improvement scale. CONCLUSIONS: Our data confirm the long-term durability of vaginal vault prolapse repair with ASC. PMID- 26992725 TI - Female pelvic organ prolapse using pessaries: systematic review. AB - INTRODUCTION AND HYPOTHESIS: The purpose of this systematic review is to assess the impact of pessary use on the quality of life of women with pelvic organ prolapse, and to determine the satisfaction rate and rationale for discontinuation. METHODS: This review is recorded in the PROSPERO database under number CRD42015023384. The criteria for inclusion were observational study; cross section; cohort study; randomized controlled trial; study published in English, Portuguese, and Spanish; and study whose participants are women with female pelvic organ prolapse treated using a pessary. We did not include limitations on the year of publication. The criteria for exclusion included studies that did not include the topic, bibliographic or systematic reviews and articles that did not use validated questionnaires. The MeSH terms were "Pelvic Organ Prolapse AND Pessaries AND Quality of Life" OR "Pessary AND Quality of Life" OR "Pessaries". RESULTS: We found 89 articles. After the final analyses, seven articles were included. All articles associated pessary use with improved quality of life, and all used only validated questionnaires. Over half of the women continued using the pessary during the follow-up with acceptable levels of satisfaction. The main rationales for discontinuation were discomfort, pain in the area, and expulsion of the device. CONCLUSION: This systematic review demonstrates that the pessary can produce a positive effect on women's quality of life and can significantly improve sexual function and body perception. PMID- 26992726 TI - Does age affect the outcome of suburethral tape surgery? The importance of national registries in answering bigger questions. AB - INTRODUCTION AND HYPOTHESIS: The objective of this article was to use the British Society of Urogynaecology (BSUG) database to assess the impact of age on success rates and insertion complications of suburethral tapes for primary procedures using the Patient Global Impression of Improvement (PGII) as the primary endpoint. METHODS: We carried out a retrospective analysis of data at a national level (BSUG database) using PGII as the primary outcome measure. Secondary outcomes included improvement in stress incontinence and complications from surgery. All episodes of suburethral tapes on the database were extracted and analysis was by decade of life. RESULTS: A total of 7,600 cases were identified on the database, of which 757 were in women over 70 years of age, with 119 in women over 80. Just over 80 % of the cases on the database involved retropubic and just under 20 % transobturator tapes. Short-term follow-up was available for 54 % of the cases. The PGII remained high in all age groups, but did decrease slightly with age, with more than 90 % of women under 50 scoring highly, which reduced to 70 % in those over 80. Improvement in stress incontinence was globally high, with 98 % scoring highly in the women aged under 50 and 85 % in the 80+ group. This suggests that the suburethral tapes worked well in treating stress incontinence. Reassuringly, complications did not increase with age, although short-term voiding difficulties were higher with increasing age. CONCLUSION: Contributing to national databases gives useful information that may be difficult to ascertain from RCTs. Suburethral tapes appear to have good efficacy and low complications with increasing age. PMID- 26992727 TI - Effect of vaginal estrogen on pessary use. AB - INTRODUCTION AND HYPOTHESIS: Many providers recommend concurrent estrogen therapy with pessary use to limit complications; however, limited data exist to support this practice. We hypothesized that vaginal estrogen supplementation decreases incidence of pessary-related complications and discontinuation. METHODS: We performed a retrospective cohort study of women who underwent a pessary fitting from 1 January 2007 through 1 September 2013 at one institution; participants were identified by billing code and were eligible if they were postmenopausal and had at least 3 months of pessary use and 6 months of follow-up. All tests were two sided, and P values < 0.05 were considered statistically significant. RESULTS: Data from 199 women were included; 134 used vaginal estrogen and 65 did not. Women who used vaginal estrogen had a longer median follow-up time (29.5 months) compared with women who did not (15.4 months) and were more likely to have at least one pessary check (98.5 % vs 86.2 %, P < 0.001). Those in the estrogen group were less likely to discontinue using their pessary (30.6 % vs 58.5 %, P < 0.001) and less likely to develop increased vaginal discharge than women who did not [hazard ratio (HR) 0.31, 95 % confidence interval (CI) 0.17 0.58]. Vaginal estrogen was not protective against erosions (HR 0.93, 95 % CI 0.54-1.6) or vaginal bleeding (HR 0.78, 95 % CI 0.36-1.7). CONCLUSIONS: Women who used vaginal estrogen exhibited a higher incidence of continued pessary use and lower incidence of increased vaginal discharge than women who did not. PMID- 26992728 TI - Safety and efficacy of single-incision sling for female stress urinary incontinence: 3 years' results. AB - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to investigate the success and complication rates of single-incision sling for treating stress urinary incontinence (SUI), with a 3-year follow-up. METHODS: This study comprised 173 female patients with SUI or mixed urinary incontinence (MUI) with dominant SUI who underwent minisling procedure. All patients had positive cough stress test preoperatively; they were followed up for 3 years after surgery (1, 3, 6, 12 months, and yearly). RESULTS: Total follow-up was 36 months, and mean age 51 years (44-77); 128 (74 %) patients presented SUI and 45 (26 %) MUI. Objective and subjective cure and failure rates were 83.8 % (145 cases), 6.4 % (11 cases), and 9.8 % (17 cases), respectively. There were no differences in cure rates between 1 and 3 years. Mean body mass index was 28.7 (26.1-35.2), and mean operating time 7.9 min. (6.5-11.9). There were no major intraoperative complications. Eleven patients (6.4 %) had de novo urge incontinence that resolved using anticholinergic drugs; no patient had urinary retention. Vaginal mesh extrusion was reported in nine (5.2 %) patients. CONCLUSIONS: The minisling system attained high success rates at 3 years' follow-up. The procedure was easy to learn and has lower complication rate. PMID- 26992729 TI - Long-term follow-up of sexual function in women before and after tension-free vaginal tape operation for stress urinary incontinence. AB - INTRODUCTION: This prospective study investigates sexual function in women after a tension-free vaginal tape (TVT) operation and compares short-term and long-term effects. METHODS: Sixty-three women had a TVT operation performed at Aalborg University Hospital, Department of Gynecology and Obstetrics, between November 2008 and June 2010. Patients completed the Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) before undergoing surgery, 6 months postoperatively, and at the long-term follow-up (mean 4 years and 9 months). RESULTS: Forty-four women completed the two questionnaires all three times. Preoperatively, mean PISQ-12 was 33.8 [95% confidence interval (CI) 28.9-38.6] and the ICIQ-UI SF was 15.2 (14.4-16.0). Postoperatively the PISQ-12 increased significantly and the ICIQ-UI-SF decreased significantly, to 36.7 (31.5-41.9) and 2.5 (1.3-3.8), respectively, at the 6 months follow-up and 35.8 (33.6-38.1) and 4.9 (3.4-6.3), respectively, at the long-term follow-up. The greates improvement was in the physical domain of the PISQ-12. Women experienced less negative emotional reactions during intercourse, less coital incontinence, and less fear of being incontinent during intercourse after the TVT operation. CONCLUSION: This study shows that a woman's sex life does not deteriorate after a TVT operation, that their sexual function improves somewhat, and that results are sustained over time. PMID- 26992730 TI - Crohn disease and pregnancy: a case report of an acute abdomen. PMID- 26992731 TI - Publication Trends Over 55 Years of Behavioral Genetic Research. AB - We document the growth in published papers on behavioral genetics for 5-year intervals from 1960 through 2014. We used 1861 papers published in Behavior Genetics to train our search strategy which, when applied to Ovid PsychINFO, selected more than 45,000 publications. Five trends stand out: (1) the number of behavioral genetic publications has grown enormously; nearly 20,000 papers were published in 2010-2014. (2) The number of human quantitative genetic (QG) publications (e.g., twin and adoption studies) has steadily increased with more than 3000 papers published in 2010-2014. (3) The number of human molecular genetic (MG) publications increased substantially from about 2000 in 2000-2004 to 5000 in 2005-2009 to 9000 in 2010-2014. (4) Nonhuman publications yielded similar trends. (5) Although there has been exponential growth in MG publications, both human and nonhuman QG publications continue to grow. A searchable resource of this corpus of behavioral genetic papers is freely available online at http://www.teds.ac.uk/public_datasets.html and will be updated annually. PMID- 26992732 TI - Review of present knowledge on machine milking and intensive milk production in dromedary camels and future challenges. AB - The camel dairy industry has gone through major development in the last decade. The world's first large-scale camel dairy farm was established 10 years ago in Dubai, United Arab Emirates, and since then, several commercial and scientific projects have been started, and more studies have been published demonstrating increasing interest in camel milk. The aims of this paper are to summarize relevant published data on factors influencing milk production under intensive management, compare those with our own observations obtained from Emirates Industry for Camel Milk and Products (EICMP), and highlight areas of research that are indispensable for further development. As in other species, the most important factors influencing milk yield are genetic and individual variation, age, parity, stage of lactation, nutrition, management, season, photoperiod, etc. However, the precise role of the various factors has not been thoroughly studied in camels and based on our understanding of the basic physiological processes, endocrine control is minimal. In addition, machine milking of dromedaries is still at early stage and requires research for improvement of the technology and defining factors affecting and improving milk ejection. The role of environment (like photoperiod, nutrition) should also be investigated as there is significant annual variation both in milk quantity and quality that might influence the processing characteristics of raw camel milk. The large pool of animals and thoroughly recorded data at EICMP provide an excellent opportunity for increasing milk production and improving milk quality using various methods, like feeding, management, reproduction, selection, and breeding. PMID- 26992734 TI - Optimal management of on-farm resources in small-scale dairy systems of Central Mexico: model development and evaluation. AB - This study evaluates the available on-farm resources of five case studies typified as small-scale dairy systems in central Mexico. A comprehensive mixed integer linear programming model was developed and applied to two case studies. The optimal plan suggested the following: (1) instruction and utilization of maize silage, (2) alfalfa hay making that added US$140/ha/cut to the total net income, (3) allocation of land to cultivated pastures in a ratio of 27:41(cultivated pastures/maize crop) rather than at the current 14:69, and dairy cattle should graze 12 h/day, (4) to avoid grazing of communal pastures because this activity represented an opportunity cost of family labor that reduced the farm net income, and (5) that the highest farm net income was obtained when liquid milk and yogurt sales were included in the optimal plan. In the context of small-scale dairy systems of central Mexico, the optimal plan would need to be implemented gradually to enable farmers to develop required skills and to change management strategies from reliance on forage and purchased concentrate to pasture-based and conserved forage systems. PMID- 26992733 TI - Identification of bovine viral diarrhea virus infection in Saanen goats in the Republic of Korea. AB - Bovine viral diarrhea virus (BVDV) is one of the most important viral pathogens of livestock and causes substantial economic losses to the livestock industry worldwide. BVDV is not necessarily species specific and is known to infect domesticated and wild ruminants. In the present study, BVDV infection was identified in two Saanen goats from one farm, and two different viral subtypes were found, BVDV-1a and BVDV-2a. Each isolate was closely related to cattle isolates identified in the Republic of Korea. The two sequences obtained in this study were not consistent with border disease virus (BDV). The incidence of BVDV in this farm apparently occurred in the absence of contact with cattle and may be associated with grazing. This study demonstrates that BVDV infection may be possible to transmit among goats without exposure to cattle. Therefore, this result indicates that Saanen goats may act as natural reservoirs for BVDV. This is the first report of BVDV-1a infection in a Saanen goat. PMID- 26992735 TI - Performance of growing rabbits fed increasing levels of discarded Salvia hispanica L. (chia) seed. AB - This experiment was carried out to evaluate the effect of including five levels of discarded chia seed (DCS) on growth, energy, and economic efficiency in rabbits. Fifty crossbred (New Zealand * Californian) weaning rabbits, weighing 798 +/- 170 g, were randomly assigned to the following treatments: 0 % (control), 10 % (Ch10), 20 % (Ch20), 30 % (Ch30), and 40 % (Ch40) of DCS. Ten unsexed rabbits were allocated to each treatment and housed individually in cages; the experimental period was 6 weeks. There were no statistically significant differences between treatments in final body weight (2050 g), body weight gain (30 g/rabbit/day), and carcass weight (1010 g); however, feed intake (91 g/rabbit/day in Ch20 vs. 80 g/rabbit/day in Ch40), feed conversion ratio (2.77 in control and Ch40 vs. 2.95 in Ch10, Ch20, and Ch30), energy conversion ratio (32 MJ/kg in Ch20 vs. 29 MJ/kg on average in control, Ch10, Ch20, Ch30, and Ch40), and economic efficiency (358 % in control vs. 433 % in Ch40) showed differences (P < 0.05) between treatments. Discarded chia seed can be included up to 40 % in growing rabbit diets without any adverse effects on growth and carcass weight, and increased economic efficiency. PMID- 26992737 TI - Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. PMID- 26992736 TI - First results on small ruminant brucellosis and tuberculosis and caprine arthritis-encephalitis in El Salvador. AB - This paper reports a first-time study performed in El Salvador on the presence or absence of antibodies to three important animal diseases in small ruminants. The work was conducted in the west and central departments of the country, selecting 42 and 43 cantons with an existing sheep and goat population, respectively. Serum samples were collected from 396 sheep and 335 goats and tested for seropositivity to Brucella (B.) spp. The specimens from goats were also tested for antibodies to caprine arthritis-encephalitis (CAE) virus. Four (1 %) sheep and none of the goats were seropositive by Rose Bengal test. All animals were negative by indirect ELISA (iELISA) for B. abortus. All animals were negative by iELISA for CAE. A total of 383 sheep and 330 goats underwent the single intradermal cervical tuberculin (SICT) test for tuberculosis. Seventy (18 %) sheep and 43 (13 %) goats reacted to the SICT test. Those reactors were subjected to the single intradermal comparative cervical tuberculin (SICCT) test, and one (0.3 %) goat was deemed to be a positive reactor. No mycobacteria were diagnosed in concluding analyses, and further studies are considered necessary to determine the prevalence of the investigated diseases. Additionally, it is recommended that small ruminants should be included in the national eradication program on bovine brucellosis and tuberculosis to prevent potential reservoirs. PMID- 26992739 TI - The Impact Factor of Radiological Journals: Associations with Journal Content and Other Characteristics Over a Recent 12-Year Period. AB - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the trends in the impact factor (IF) of radiological journals over a recent 12-year period, including associations between IF and journal topic. MATERIALS AND METHODS: Journal Citation Reports (JCR) was used to identify all biomedical journals and all radiological journals (assigned a JCR category of "Radiology, Nuclear Medicine, & Medical Imaging"), along with journal IF, in 2003 and 2014. Radiological journals were manually classified by topic. Trends in median IF (mIF) were assessed. RESULTS: The number of radiological journals increased from 83 (2003) to 125 (2014) (all biomedical journals: 5907 to 8718, respectively). mIF of radiological journals increased from 1.42 (2003) to 1.75 (2014) (all biomedical journals: 0.93 to 1.46, respectively). The most common topic among new radiological journals was general (nonspecialized) radiology (8). Five new radiological journals in 2014 were in topics (cancer imaging and molecular imaging) having no journals in 2003. mIF of general radiological journals was 1.49. Topics having highest mIF were cardiac imaging (2.94), optics (2.86), molecular imaging (2.77), radiation oncology (2.60), and neuroradiology (2.25). Topics with lowest mIF were ultrasound (1.19) and interventional radiology (1.44). Topics with the largest increase in mIF were cardiac imaging (from 1.17 to 2.94) and neuroradiology (from 1.07 to 2.25). CONCLUSIONS: Radiological journals exhibited higher mIF than biomedical journals overall. Among radiological journals, subspecialty journals had highest mIF. While a considerable number of new radiological journals since 2003 were general radiology journals having relatively low IF, there were also new journal topics representing emerging areas of subspecialized radiological research. PMID- 26992738 TI - Prostate Cancer Detection Using Computed Very High b-value Diffusion-weighted Imaging: How High Should We Go? AB - RATIONALE AND OBJECTIVES: The aim of this study was to assess prostate cancer detection using a broad range of computed b-values up to 5000 s/mm(2). MATERIALS AND METHODS: This retrospective Health Insurance Portability and Accountability Act-compliant study was approved by an institutional review board with consent waiver. Forty-nine patients (63 +/- 8 years) underwent 3T prostate magnetic resonance imaging before prostatectomy. Examinations included diffusion-weighted imaging (DWI) with b-values of 50 and 1000 s/mm(2). Seven computed DWI image sets (b-values: 1000, 1500, 2000, 2500, 3000, 4000, and 5000 s/mm(2)) were generated by mono-exponential fit. Two blinded radiologists (R1 [attending], R2 [fellow]) independently evaluated diffusion weighted image sets for image quality and dominant lesion location. A separate unblinded radiologist placed regions of interest to measure tumor-to-peripheral zone (PZ) contrast. Pathologic findings from prostatectomy served as reference standard. Measures were compared between b values using the Jonckheere-Terpstra trend test, Spearman correlation coefficient, and generalized estimating equations based on logistic regression for correlated data. RESULTS: As b-value increased, tumor-to-PZ contrast and benign prostate suppression for both readers increased (r = +0.65 to +0.71, P <= 0.001), whereas anatomic clarity, visualization of the capsule, and visualization of peripheral-transition zone edge decreased (r = -0.69 to -0.75, P <= 0.003). Sensitivity for tumor was highest for R1 at b1500-3000 (84%-88%) and for R2 at b1500-2500 (70%-76%). Sensitivities for both pathologic outcomes were lower for both readers at both b1000 and the highest computed b-values. Sensitivity for Gleason >6 tumor was highest for R1 at b1500-3000 (90%-93%) and for R2 at 1500 2500 (78%-80%). The positive predictive value for tumor for R1 was similar from b1000 to 4000 (93%-98%) and for R2 was similar from b1500 to 4000 (88%-94%). CONCLUSIONS: Computed b-values in the range of 1500-2500 s/mm(2) (but not higher) were optimal for prostate cancer detection; b-values of 1000 or 3000-5000 exhibited overall lower performance. PMID- 26992740 TI - "Do you expect me to receive PTSD care in a setting where most of the other patients remind me of the perpetrator?": Home-based telemedicine to address barriers to care unique to military sexual trauma and veterans affairs hospitals. AB - Home-based telemedicine (HBT) is a validated method of evidence-based treatment delivery for posttraumatic stress disorder (PTSD), and justification for its use has centered on closing gaps related to provider availability and distance to treatment centers. However, another potential use of HBT may be to overcome barriers to care that are inherent to the treatment environment, such as with female veterans who have experienced military sexual trauma (MST) and who must present to VA Medical Centers where the majority of patients share features with perpetrator (e.g. gender, clothing) and may function as reminders of the trauma. Delivering evidence-based therapies to female veterans with MST-related PTSD via HBT can provide needed treatment to this population. This manuscript describes an ongoing federally funded randomized controlled trial comparing Prolonged Exposure (PE) delivered in-person to PE delivered via HBT. Outcomes include session attendance, satisfaction with services, and clinical and quality of life indices. It is hypothesized that based on intent-to-treat analyses, HBT delivery of PE will be more effective than SD at improving both clinical and quality of life outcomes at post, 3-, and 6-month follow-up. This is because 'dose received', that is fewer sessions missed, and lower attrition, will be observed in the HBT group. Although the current manuscript focuses on female veterans with MST related PTSD, implications for other populations facing systemic barriers are discussed. PMID- 26992741 TI - Ling Zhi-8 reduces lung cancer mobility and metastasis through disruption of focal adhesion and induction of MDM2-mediated Slug degradation. AB - We recently reported that recombinant Ling Zhi-8 (rLZ-8), a medicinal mushroom Ganoderma lucidum recombinant protein, effectively prevents lung cancer cells proliferation in vivo mice model. In our current study, we demonstrated that rLZ 8 suppressed tumor metastasis and increased the survival rate in Lewis lung carcinoma cell-bearing mice. The epithelial to mesenchymal transition (EMT) process is regarded as the critical event in tumor metastasis. Herein, we showed that rLZ-8 effectively induced changes in EMT by interfering with cell adhesion and focal adhesion kinase (FAK) functions in lung cancer cells. Slug, a transcription factor, represses E-cadherin transcription and is regarded as a critical event in EMT and tumor metastasis. Functional studies revealed that downregulation of Slug as a result of rLZ-8-induced FAK inactivation enhanced E cadherin expression and repressed cancer cell mobility. Moreover, we found that rLZ-8 enhanced the ubiquitination proteasome pathway (UPP)-mediated degradation of Slug in CL1-5 cells. Mechanistically, we demonstrated that rLZ-8 promoted the interaction between MDM2 and Slug, resulting in Slug degradation; however, MDM2 shRNA abolished rLZ-8-enhanced Slug degradation. This study is the first to determine anti-metastatic activity of rLZ-8 and its potential mechanism, with how the regulation of EMT and cell mobility is via the negative modulation of FAK, and thereby leading to the ubiquitination and degradation of Slug. Our findings suggest that the targets of FAK play a key role in metastasis. Moreover, rLZ-8 may be useful as a chemotherapeutic agent for treating lung cancer. PMID- 26992742 TI - Intracardiac thrombus and Murphy's law: Reflections on a clinical dilemma. AB - We discuss the case of a 49-year-old patient with left ventricular systolic dysfunction and a large, mobile and protruding apical thrombus. In spite of anticoagulation treatment, extensive and clearly defined systemic embolization occurred. We discuss the current evidence on the treatment of intracardiac thrombus with high risk of systemic embolization and propose a tailored approach to avoid potential catastrophic consequences. PMID- 26992744 TI - [Cochrane Corner: Intra-aortic balloon pump in patients with cardiogenic shock following myocardial infarction]. AB - Improvement of hemodynamic parameters is the rationale for the use of intra aortic balloon pump counterpulsation (IABP) in patients with cardiogenic shock following acute myocardial infarction (MI). This Cochrane systematic review evaluated the impact of this intervention in reducing mortality. Seven randomized controlled trials with a total of 790 patients were included (four using medical therapy as a comparator, and three comparing IABP with other ventricular assist devices). IABP did not reduce mortality in either the short or long term. Therefore, the systematic use of IABP in patients with cardiogenic shock following MI cannot be recommended. PMID- 26992743 TI - [Primary Malignant Cardiac Tumors: Surgical results]. AB - OBJECTIVE: To characterize primary malignant cardiac tumors operated on in our center and to analyze patient survival. METHODS: Between January 1994 and August 2014, 123 patients with cardiac tumors underwent surgery, of which 12 (9.8%) were primary malignant tumors - eight sarcomas (67%), three B-cell lymphomas (25%) and one epithelioid hemangioendothelioma (8.3%). The tumor affected the left atrium in five cases (42%), the right atrium in four (33%), the right ventricle in two (17%) and the pulmonary valve in one (8%). Patients' mean age was 55.4 +/- 16.9 years, 67% were female and 75% presented in New York Heart Association class III IV. RESULTS: Resection was complete (negative margins) in five cases and partial in seven (five sarcomas and two lymphomas), and 11 patients needed adjuvant therapy, surgery alone being curative in only one (epithelioid hemangioendothelioma). Mean follow-up was 41.7 +/- 61.3 months: 24.8 +/- 30.0 months (3.8-95.7) for sarcomas, 70.1 +/- 118.0 months (1-206.3) for lymphomas and 91.9 months for the epithelioid hemangioendothelioma. During follow-up, 10 patients died (83%) and two were alive (17%). Overall survival at 30 days, six months, one year and two years was 91.7%, 66.7%, 58.3% and 41.7%, respectively. In the sarcoma group, 1-year and 2-year survival were 62.5% and 37.5%, respectively. CONCLUSIONS: Resection of primary malignant cardiac tumors, even partial, is safe, provides relief of obstructive symptoms and improves quality of life, but is rarely curative and has a low survival rate. Due to the rarity of such tumors, a multicenter database could improve knowledge and help clarify the indications for cardiac surgery as a treatment option. PMID- 26992745 TI - Left ventricular longitudinal systolic dysfunction is associated with right atrial dyssynchrony in heart failure with preserved ejection fraction. AB - OBJECTIVE: We aimed in this study to assess the role of longitudinal left ventricular (LV) systolic function in heart failure with preserved ejection fraction (HFpEF) in delayed intra- and interatrial conduction time. METHODS: In 85 consecutive patients with HFpEF (age 60+/-11 years, ejection fraction [EF] >=45%), a complete M-mode echocardiographic and tissue Doppler imaging (TDI) study was performed. The times from the onset of the P wave on the ECG to the beginning of the A' wave (PA) from the lateral and septal mitral and tricuspid annuli on TDI were recorded. The difference between these intervals gave the intra- and interatrial dyssynchrony. Based on mitral annular plane systolic excursion (MAPSE), patients were classified as having HFpEF with impaired (MAPSE <=1.2 cm) or normal (MAPSE >1.2 cm) longitudinal systolic function. RESULTS: Patients with impaired MAPSE were older (p<0.001), had higher LV mass index (p<0.001), greater left atrial (LA) minimum volume (p=0.007), reduced left atrial EF (p<0.001), higher E/e' ratio (p=0.002), reduced lateral and septal e' wave (p=0.005 and p=0.006, respectively), prolonged tricuspid PA' (p=0.03) and significantly increased right atrial (RA) dyssynchrony (p=0.001) compared with normal MAPSE. MAPSE correlated with RA dyssynchrony (r=-0.40, p<0.001) but not with interatrial and LA dyssynchrony. CONCLUSION: In patients with HFpEF and impaired MAPSE, RA dyssynchrony is increased, compared to those with normal MAPSE. As patients with RA dyssynchrony are at higher risk for arrhythmia, assessment of this dyssynchrony may help to improve treatment, as well as to predict outcome in these patients. PMID- 26992746 TI - The nutrient load from food waste generated onboard ships in the Baltic Sea. AB - The combination of the sensitive characteristics of the Baltic Sea and the intense maritime traffic makes the marine environment vulnerable to anthropogenic influences. The theoretical scenario calculated in this study shows that the annually generated food waste onboard ships in traffic in the Baltic Sea contains about 182tonnes of nitrogen and 34tonnes of phosphorus. Today, all food waste generated onboard can be legally discharged into the marine environment at a distance of 12NM from the nearest land. The annual load of nitrogen contained in the food waste corresponds to 52% of load of nitrogen from the ship-generated sewage. Future regulations for sewage discharge in the Baltic Sea will require significant reduction of total nitrogen and phosphorus released. The contribution of nutrients from food waste compared to sewage will therefore be relatively larger in the future, if food waste still can be legally discharged. PMID- 26992747 TI - Bioremediation technologies for polluted seawater sampled after an oil-spill in Taranto Gulf (Italy): A comparison of biostimulation, bioaugmentation and use of a washing agent in microcosm studies. AB - One of the main challenges of bioremediation is to define efficient protocols having a low environmental impact. We have investigated the effect of three treatments in oily-seawater after a real oil-spill occurred in the Gulf of Taranto (Italy). Biostimulation with inorganic nutrients allowed the biodegradation of the 73+/-2.4% of hydrocarbons, bioaugmentation with a selected hydrocarbonoclastic consortium consisting of Alcanivorax borkumensis, Alcanivorax dieselolei, Marinobacter hydrocarbonoclasticus, Cycloclasticus sp. 78-ME and Thalassolituus oleivorans degraded 79+/-3.2%, while the addition of nutrients and a washing agent has allowed the degradation of the 69+/-2.6%. On the other hand, microbial community was severely affected by the addition of the washing agent and the same product seemed to inhibit the growth of the majority of strains composing the selected consortium at the tested concentration. The use of dispersant should be accurately evaluated also considering its effect on the principal actors of biodegradation. PMID- 26992748 TI - Trace metal bioavailability in sediments from a reference site, Ribeira Bay, Brazil. AB - Surface sediments were collected near potential contamination sources impacting Ribeira Bay (Brazil), a system considered as a 'reference site' for trace metals. Physicochemical properties (pH and Eh), grain size and concentrations of total organic carbon (TOC), total phosphorus (TP), acid-volatile sulfides (AVS) and simultaneously-extracted metals (Fe, Mn, Cd, Cu, Ni, Pb and Zn) were analyzed. Although relatively low metal concentrations were found, correlations of Zn and Ni with high TP levels suggested an association with sewage inputs, while other metals presented associations with specific geochemical carriers (TOC, Fe and Mn compounds). AVS levels exceeding those of the sums of Cd, Cu, Ni, Pb and Zn (SigmaSEM) by at least one order of magnitude and TOC-normalized differences between SigmaSEM and AVS ((SigmaSEM-AVS)/fOC) near to or below than -200MUmolgOC( 1) indicated that there were sufficient AVS and TOC levels to control trace metal bioavailability in sediment pore water. PMID- 26992749 TI - A-DROP: A predictive model for the formation of oil particle aggregates (OPAs). AB - Oil-particle interactions play a major role in removal of free oil from the water column. We present a new conceptual-numerical model, A-DROP, to predict oil amount trapped in oil-particle aggregates. A new conceptual formulation of oil particle coagulation efficiency is introduced to account for the effects of oil stabilization by particles, particle hydrophobicity, and oil-particle size ratio on OPA formation. A-DROP was able to closely reproduce the oil trapping efficiency reported in experimental studies. The model was then used to simulate the OPA formation in a typical nearshore environment. Modeling results indicate that the increase of particle concentration in the swash zone would speed up the oil-particle interaction process; but the oil amount trapped in OPAs did not correspond to the increase of particle concentration. The developed A-DROP model could become an important tool in understanding the natural removal of oil and developing oil spill countermeasures by means of oil-particle aggregation. PMID- 26992750 TI - Comparison of passive-beam proton therapy, helical tomotherapy and 3D conformal radiation therapy in Hodgkin's lymphoma female patients receiving involved-field or involved site radiation therapy. AB - PURPOSE: Second cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy. PATIENTS AND METHODS: Fourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20Gy/10Gy. RESULTS: Mean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15Gy with the V20Gy equal to 16.4%, compared to 19.7% for proton therapy (P=0.01) or 22.4% with 3D conformal radiation therapy (P<0.01). Volumes of lung receiving doses below 15Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V10Gy=37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10Gy or more than 4Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V4Gy representing more than a third of one breast volume with helical tomotherapy. CONCLUSIONS: Helical tomotherapy achieved a better protection to the lungs for doses above 15Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings. PMID- 26992752 TI - Deep venous reflux definitions and associated clinical and physiological significance. AB - BACKGROUND: Deep venous reflux (DVR) is often a poorly defined clinical entity. The extent of DVR that must occur for it to be clinically and hemodynamically important is not clear and is usually confounded by the presence of superficial venous reflux. This study aims to investigate the effect of the extent of DVR on clinical and hemodynamic parameters while controlling for the presence of superficial reflux. METHODS: We performed a cross-sectional study, using a prospectively designed data set obtained from patients presenting to a vascular laboratory for lower limb venous assessment. Age, gender, duplex ultrasound assessment of the deep and superficial systems, CEAP clinical class, and venous filling index (VFI) measurements were obtained. A classification of axial DVR is described, based on the level of continuous reflux occurring in the vertical axis as detected by duplex ultrasound: axial 0 (no deep reflux), axial 1 (common femoral vein only), axial 2 (to any level of the femoral vein), axial 3 (to the level of the popliteal vein), and axial 4 (into the calf veins) A subset of segmental reflux is also defined. RESULTS: This study included 3122 limbs from 2349 subjects. Limbs with increasing axial level were more likely to have CEAP 4 6 (axial 0: 294 [37.2%]; axial 1: 520 [41.6%]; axial 2: 82 [41.2%]; axial 3: 92 [59.7%]; axial 4: 148 [64.9%], P value for trend <.0001). This relationship remained highly significant following adjustment for superficial reflux and demographic variables. Compared with limbs with no DVR, the adjusted odds ratio for having CEAP 4-6 was 2.10 (1.25-3.51; P < .0048) for limbs with axial level 3 and 3.07 (1.94-4.88, P < .0001) for limbs with axial level 4. Similarly after adjustment, predicted mL/s increases in VFI were significant (P < .0001) for level 1 (1.19 [1.08-1.31]), level 3 (1.53 [1.31-1.78]), and level 4 (1.74 [1.51 1.95]). Segmental reflux, when extensive, also contributed to the risk of more severe disease. CONCLUSIONS: Deep axial reflux to the level of the knee and calf is associated with more severe venous disease and greater VFI, independently of reflux in the superficial system. A system of classification of DVR is recommended. PMID- 26992751 TI - Glucocorticoids alter neuronal differentiation of human neuroepithelial-like cells by inducing long-lasting changes in the reactive oxygen species balance. AB - Prenatal exposure to excess glucocorticoid has been shown to have adverse effects on the developing nervous system that may lead to alterations of fetal and adult neurogenesis, resulting in behavioral changes. In addition, an imbalance of the redox state, with an increased susceptibility to oxidative stress, has been observed in rodent neural stem cells exposed to the synthetic glucocorticoid analog dexamethasone (Dex). In the present study, we used the induced pluripotent stem cells (IPSC)-derived lt-NES AF22 cell line, representative of the neuroepithelial stage in central nervous system development, to investigate the heritable effects of Dex on reactive oxygen species (ROS) balance and its impact on neuronal differentiation. By analysing gene expression in daughter cells that were never directly exposed to Dex, we could observe a downregulation of four key antioxidant enzymes, namely Catalase, superoxide dismutase 1, superoxide dismutase 2 and glutathione peroxidase7, along with an increased intracellular ROS concentration. The imbalance in the intracellular REDOX state was associated to a significant downregulation of major neuronal markers and a concomitant increase of glial cells. Interestingly, upon treatment with the antioxidant N acetyl-cysteine (NAC), the misexpression of both neuronal and glial markers analyzed was recovered. These novel findings point to the increased ROS concentration playing a direct role in the heritable alterations of the differentiation potential induced by Dex exposure. Moreover, the data support the hypothesis that early insults may have detrimental long-lasting consequences on neurogenesis. Based on the positive effects exerted by NAC, it is conceivable that therapeutic strategies including antioxidants may be effective in the treatment of neuropsychiatric disorders that have been associated to increased ROS and impaired neurogenesis. PMID- 26992753 TI - Measurements of calf muscle oxygenation during standing and exercise in patients with primary valvular insufficiency. AB - OBJECTIVE: Despite the established role of the calf muscle pump for preventing chronic venous disorders, hemoglobin flow in the calf muscle is poorly understood. Near-infrared spectroscopy (NIRS) provides continuous noninvasive monitoring of changes in tissue-oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) levels. The purpose of this study was to investigate the changes in calf muscle O2Hb and HHb levels during standing and exercise in patients with primary valvular insufficiency (PVI). METHODS: Eighty-three limbs in 81 patients with PVI were enrolled. The clinical manifestations of these patients were categorized according to the CEAP (Clinical, Etiologic, Anatomical, and Pathophysiologic) classification, and patients were divided into group I (C1 3S,Ep,As,d,p,Pr) and group II (C4-6S,Ep,As,d,p,Pr). Moreover, to assess the severity of PVI, the revised Venous Clinical Severity Score (VCSS) was employed. NIRS was used to measure changes in the calf muscle O2Hb and HHb levels. On standing, increases in O2Hb and HHb were calculated by subtracting the baseline value from the maximum value (DeltaO2Hbst and DeltaHHbst). The time elapsed until the maximum increases in O2Hb and HHb concentrations (TO2Hbst, and THHbst) were also measured. During 10 tiptoe movements, the relative change in O2Hb was calculated by subtracting the value measured at the end of exercise from the value measured at the beginning of exercise (DeltaO2Hbex). On the other hand, 10 tiptoe movements produced venous expulsion (DeltaHHbEex) and a subsequent retention (DeltaHHbRex). The oxygenation index (HbD; HbD = O2Hb - HHb) was also calculated at the end of standing and 10 tiptoe movements (DeltaHbDst and DeltaHbDex). RESULTS: Among the 83 limbs evaluated, 48 were classified as group I and 35 as group II. Standing caused increases in the levels of both DeltaO2Hbst and DeltaHHbst. However, there were no significant differences in these increases between the two groups. In contrast, the TO2Hbst was significantly reduced in group II in comparison with group I (55 +/- 29 vs 36 +/- 30 seconds; P = .007). During 10 tiptoe movements, a decrease in O2Hb concentration was observed, and there was no significant difference in DeltaO2Hbex between group I and group II. In contrast, the DeltaHHbRex was significantly increased in group II compared with group I (6 +/- 7 vs 9 +/- 6 MUmol/L; P = .013). Furthermore, falls in DeltaHbDex were more pronounced in group II (7 +/- 16 vs -7 +/- 16 MUmol/L; P = .001). A statistically significant correlation was found between C of CEAP and the VCSS (r = 0.778; P < .001). Moreover, NIRS-derived TO2Hbst (r = -0.312; P < .01) and DeltaHbDex (r = -0.332; P < .01) showed moderate inverse correlations with C of CEAP. Similarly, NIRS-derived DeltaHbDex (r = -0.501; P < .001) had a strong inverse correlation, and DeltaHbDst (r = -0.383; P < .001) and TO2Hbst (r = -0.378; P < .001) had moderate inverse correlations with VCSS. CONCLUSIONS: Changes in O2Hb and HHb concentrations differ according to CEAP manifestation and VCSS. These data offer new insights into calf muscle hemodynamics at the microcirculation level in patients with PVI. PMID- 26992754 TI - Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy, and surgical stripping for great saphenous varicose veins with 3-year follow-up. AB - INTRODUCTION: This study compares the outcome 3 years after treatment of varicose veins by endovenous laser ablation (EVLA), radiofrequency ablation, ultrasound guided foam sclerotherapy (UGFS), or surgery by assessing recurrence, Venous Clinical Severity Score (VCSS), and quality of life (QOL). METHODS: A total of 500 patients (580 legs) were randomized to one of the three endovenous treatments or high ligation and stripping of the great saphenous vein (GSV). Follow-up included clinical and duplex ultrasound examinations and VCSS and QOL questionnaires. Kaplan-Meier (KM) life-table analysis was used. P values below .05 were considered statistically significant. RESULTS: At 3 years, eight (KM estimate, 7%), eight (KM estimate, 6.8%), 31 (KM estimate, 26.4%), and eight (KM estimate, 6.5%) of GSVs recanalized or had a failed stripping procedure (more than 10 cm open refluxing part of the treated GSV; CLF, EVLA, UGFS, and stripping, respectively; P < .01). Seventeen (KM estimate, 14.9%), 24 (KM estimate, 20%), 20 (KM estimate, 19.1%), and 22 (KM estimate, 20.2%) legs developed recurrent varicose veins (P = NS). The patterns of reflux and location of recurrent varicose veins were not different between the groups. Within 3 years after treatment, 12 (KM estimate, 11.1%), 14 (KM estimate, 12.5%), 37 (KM estimate, 31.6%), and 18 (KM estimate, 15.5%) legs were retreated in the CLF, EVLA, UGFS, and stripping groups, respectively (P < .01). VCSS, SF-36, and Aberdeen QOL scores improved significantly in all the groups with no difference between the groups. CONCLUSIONS: All treatment modalities were efficacious and resulted in a similar improvement in VCSS and QOL. However, more recanalization and reoperations were seen after UGFS. PMID- 26992755 TI - Invited commentary. PMID- 26992756 TI - Endovenous laser ablation versus conventional surgery in the treatment of small saphenous vein incompetence. AB - INTRODUCTION: In this multicenter, randomized controlled trial, endovenous laser ablation (EVLA) is compared with conventional surgery for the treatment of varicose veins based on incompetence of the small saphenous vein and the saphenopopliteal junction (SPJ). METHODS: In two Dutch hospitals, 189 patients were enrolled and randomized to receive EVLA (810-nm laser) or ligation of the SPJ. End points were success rate measured with duplex ultrasound (6 weeks post treatment), perioperative pain, quality of life, duration of surgery, difficulty of surgery, complications, cosmetic results, and number of days to resume work and normal activities. Pain was measured on a visual analog scale (VAS). Quality of life was assessed using the Aberdeen Varicose Vein Questionnaire (AVVQ) and Euro Qol-5D. The follow-up duration in this article is 6 weeks. RESULTS: One hundred seventy-five patients have been treated and analyzed. One hundred eighteen patients (67%) underwent EVLA, and 57 patients (33%) underwent ligation of the SPJ. The patient characteristics were similar in both groups. In the surgery group, 21% residual incompetence of the SPJ was seen after 6 weeks, compared with 0.9% in the laser group. Both treatment modalities reduced pain after 6 weeks. One week post-treatment, patients in the EVLA group temporarily experienced more pain compared with the surgery group (31 vs 18 on a VAS from 0 to 100). There were no significant differences between the two groups with respect to quality of life. Both treatments did show improvement in quality of life. Also with regard to the cosmetics, there were no differences, aside from the fact that patients rated their scar as more beautiful after EVLA. After EVLA, patients could return to work more quickly. The operation time was longer in the surgery group. After 2 weeks, there were significantly more neurological complications in the surgery group: 18 (31%) vs 16 (17%) patients in the EVLA group. Ten percent of patients in the surgery group developed a surgical site infection vs 0% in the EVLA group. CONCLUSIONS: EVLA provides an excellent alternative to conventional surgery in the treatment of symptomatic varicose veins due to an incompetent small saphenous vein with SPJ. EVLA has a superior immediate success rate, is easier and faster, and has fewer complications. PMID- 26992757 TI - Compression of left common iliac vein is independently associated with left-sided deep vein thrombosis. AB - OBJECTIVE: Left-sided lower extremity deep vein thrombosis (DVT) is more common than right-sided DVT. This difference was found to be caused by the compression of the left iliac common vein (LCIV). To evaluate and compare LCIV compression in unilateral DVT patients and the normal population and investigate the association of LCIV compression with the risk of left-sided DVT. METHODS: A retrospective analysis of records and computed tomography imaging was conducted in 19 right DVT, 60 left DVT, and 218 control subjects. The influences of LCIV diameter and stenosis on the risk of left DVT were investigated using logistic regression analysis. RESULTS: In control subjects, 51.8% had greater than 50% compression of the LCIV, and 24.3% had greater than 70% compression. Mean LCIV diameter was smaller in left DVT (2.39 mm) than in right DVT (6.18 mm) or normal control (5.39 mm). Mean LCIV stenosis was higher in left DVT (77.57%) than in right DVT (38.01%) or normal control (49.31%). The odds of left DVT increased by a factor of 2.69 for each millimeter decrease in LCIV diameter and 2.78 for each 10% increase in LCIV stenosis. With LCIV stenosis >75%, the risk of left DVT was associated with an 11-fold increase, and with LCIV diameter <2.5 mm, the risk was associated with a 13.5-fold increase. Unprovoked and provoked left DVT patients had similar LCIV compression, and left DVT patients had more significant LCIV compression than right DVT patients. CONCLUSIONS: LCIV compression was a normal anatomical pattern with an increased risk of left DVT. LCIV compression might be the essential and prereqisite factor for left DVT. Patients with severe LCIV compression should receive more emphasis on left DVT prophylaxis because they are the high-risk population of left DVT. PMID- 26992758 TI - Risk of asymptomatic pulmonary embolism in patients with deep venous thrombosis. AB - OBJECTIVE: The aim of our study is to evaluate the incidence of asymptomatic pulmonary embolism (PE) in patients with deep venous thrombosis (DVT), submitted to routine angiography of pulmonary vessels, and analyze the relationship between the site of DVT and extent of PE. METHODS: Between January 2006 and April 2012, 52 consecutive patients with acute inferior limb DVT were divided into two study groups composed of individuals with proximal and distal thrombotic involvement. All patients had no respiratory symptoms and were submitted to routine pulmonary computed tomography angiography for active investigation of PE. We assessed the incidence and extent of PE in both study groups. RESULTS: Thirty-eight patients (72%) had PE, detected by computed tomography angiography. The incidence of PE in patients with proximal and distal thrombosis, respectively, was 72.7% and 73.7%. Occurrence of segmental embolism was equally high in both groups, affecting 71.4% of the patients with distal thrombosis and 66.6% of the individuals with proximal DVT (P > .99). CONCLUSIONS: The incidence of asymptomatic PE observed in patients with DVT is higher than what is reported in the current literature. This supports the importance of screening and the need for high levels of suspicion regarding this complication. PMID- 26992759 TI - Decision analysis of retrievable inferior vena cava filters in patients without pulmonary embolism. AB - BACKGROUND: Retrievable filters are increasingly implanted for prophylaxis in patients without pulmonary embolism (PE) but who may be at transient risk. These devices are often not removed after the risk of PE has diminished. This study employs decision analysis to weigh the risks and benefits of retrievable filter use as a function of the filter's time in situ. METHODS: Medical literature on patients with inferior vena cava (IVC) filters and a transient risk of PE were reviewed. Weights reflecting relative severity were assigned to each adverse event. The risk score was defined as weight * occurrence rate and combines the frequency and severity for each type of adverse event. The value function in the decision model combines the following risks: (1) risk in situ; (2) risk of removal, and (3) relative risk without filters. A decreasing net risk score represents a net expected benefit, and an increasing net risk score indicates the expected harm outweighs the expected benefit. RESULTS: The net risk score reaches its minimum between day 29 and 54 postimplantation. This is consistent with an increasing net risk associated with continued use of retrievable IVC filters in patients with transient, reversible risk of PE. The results were insensitive to reasonable variations in the assessed weights and adverse event occurrence rates. CONCLUSIONS: For patients with retrievable IVC filters in whom the transient risk of PE has passed, quantitative decision analysis suggests the benefit/risk profile begins to favor filter removal between 29 and 54 days after implantation. PMID- 26992760 TI - Value of postoperative compression after mini-invasive surgical treatment of varicose veins. AB - OBJECTIVE: It is customary to recommend wearing elastic band compression or compression stockings after treatment of varicose veins. Our aim was to evaluate the benefit from wearing elastic compression stockings after surgical treatment of varicose veins. METHODS: Prospective nonrandomized study with inclusion of consecutive patients operated on for unilateral varicose veins during a 6-month period with distribution in two groups: group 1, in which the patients were wearing an 18-mm Hg thigh compression stocking from the day of the operation until the postoperative consultation and group 2, in which the patients were wearing an 18-mm Hg thigh compression stocking for only 36 hours after surgery. The evaluation of outcomes was made at the postoperative consultation and concerned pain (self-evaluation by visual analog scale) and analgesic consumption, ecchymosis (self evaluation by visual analog scale), edema (circumference of the ankle), deep or superficial venous thrombosis (ultrasound duplex), quality of life by Chronic Venous Insufficiency Quality-of-Life questionnaire, and duration of postoperative sick leave. RESULTS: Fifty patients were included in each group for a total of 100. There was no significant difference between the two groups with regard to demographics, to clinical and hemodynamic characteristics, and to the type of surgery performed (phlebectomy, 32% vs 32%; ambulatory selective varices ablation under local anesthesia, 46% vs 48%; stripping, 10% vs 12%; redo surgery for recurrence, 12% vs 8%). All the surgical procedures were carried out under tumescent local anesthesia. At the postoperative consultation, we did not observe any significant difference between group 1 and group 2 for pain score (0.6 vs 0.8; P = .35), analgesic consumption frequency (8% vs 12%; P = .50), ecchymosis score (1.3 vs 1.2; P = .49), and quality-of-life score (7.00 vs 8.64; P = .43). The circumference of the ankle was not significantly different for the side operated on before and after surgery, for group 1 (25.6 cm vs 26.2 cm; P = .30) and for group 2 (25.5 cm vs 26.2 cm; P = .28). No superficial or deep vein thrombosis was found. There was no difference in sick leave frequency (26.7% vs 32.3%; P = .57) and duration (2.6 vs 2.3 days; P = .83). CONCLUSIONS: We found no benefit from wearing the compression stocking beyond the first postoperative day for pain, ecchymosis, quality of life, and thrombosis after a mini-invasive surgical treatment for varicose veins carried out under tumescent local anesthesia with immediate ambulation. PMID- 26992761 TI - Effects of percutaneous transhepatic interventional treatment for symptomatic Budd-Chiari syndrome secondary to hepatic venous obstruction. AB - OBJECTIVE: Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder characterized by hepatic venous outflow obstruction. The management of BCS includes anticoagulation and thrombolysis, percutaneous transhepatic stent angioplasty (PTSA), and transjugular intrahepatic portosystemic shunt (TIPS), but the effect of these approaches varies greatly. The aim of our study was to retrospectively evaluate the medium-term effects of PTSA and TIPS of BCS secondary to hepatic venous outflow obstruction and to determine the critical factors affecting the efficacy. METHODS: From June 2007 to June 2012, 18 patients (15 males and 3 females; mean age, 36 +/- 9 years) with BCS (obstruction of the hepatic veins) treated by PTSA (n = 15) and TIPS (n = 3) were studied retrospectively. Clinical records were analyzed with respect to underlying disease, therapeutic interventions, complications, quality of life, and overall outcome. RESULTS: Percutaneous transhepatic interventional treatment was technically successful in all patients. In PTSA group, the primary and secondary stent patency rates were 80% and 86.7%, respectively. In the TIPS group, ascites resolved completely, and liver congestion and function were relieved greatly in all three patients. Hemodynamic features and clinical symptoms in patients with successful treatment improved significantly. Physical aspects evaluated by SF-36 were improved greatly at the end of follow-up. CONCLUSIONS: For segmental stenosis or occlusion of hepatic vein caused by thrombosis or membranous webs, PTSA should be recommended as the first choice. TIPS should be applied for diffuse stenosis or occlusion in all the hepatic veins and branches. Standard anticoagulation may promote stent patency. Quality of life after interventional treatment was improved partially, and the mental aspects need to be further investigated. PMID- 26992762 TI - Indocyanine green lymphography for evaluation of genital lymphedema in secondary lower extremity lymphedema patients. AB - OBJECTIVE: Treatment of genital lymphedema (GL) is challenging, and early diagnosis and intervention is important to prevent progression of GL. However, early treatment of GL is difficult due to a lack of appropriate evaluation methods allowing early diagnosis. We sought to develop a novel pathophysiological evaluation method for early diagnosis of GL using indocyanine green (ICG) lymphography. METHODS: This was a retrospective observational study set in a teaching hospital. Patient characteristics and ICG lymphography findings of 68 lower limb lymphedema patients secondary to gynecologic cancer treatments were reviewed. The clinical data and dermal backflow (DB) stages based on ICG lymphography findings were analyzed to compare between the left and right region with and without symptomatic GL. RESULTS: Twenty-two of 136 lateralities were symptomatic GL. Univariate analyses revealed statistically significant differences between lateralities with (n = 22) and without GL (n = 114) in the duration of leg edema (6.3 +/- 1.1 vs 3.8 +/- 0.5 years; P = .032), International Society of Lymphology stage (stage 0/1/2/3: 0/4/15/3 vs 40/32/32/10; P = .001), leg DB stage (stage 0/I/II/III/IV/V: 0/0/7/9/4/2 vs 6/35/23/29/18/3; P = .002), and genital DB stage (stage 0/I/II/III/IV: 0/0/0/20/2 vs 27/43/28/16/0; P < .001). CONCLUSIONS: ICG lymphography can clearly visualize abnormal lymph circulation in the lower abdominal and genital region. Genital DB stage based on ICG lymphography findings allows early diagnosis of GL before symptom manifestation. Further studies are needed to clarify that ICG lymphography is a key evaluation for prevention and early intervention of GL. PMID- 26992763 TI - Intravascular lipoma of the internal jugular vein. AB - Benign primary venous tumors are rare. While venous lipomas have been reported in the vena cava, their incidence in the remainder of the venous circulation is less well known. We present what we believe to be the first reported case of an intravascular lipoma arising from the internal jugular vein. The clinical presentation, imaging characteristics, and histologic features are presented. We also performed a review of the current literature. PMID- 26992764 TI - Radiotherapeutic management of the chyloperitoneum following abdominal aortic aneurysm repair. AB - Chyloperitoneum is a rare but life-threatening complication with no uniformity concerning the treatment. We present a 77-year-old male with chylous ascites after open abdominal aneurysmectomy refractory to conservative and surgical strategies. After failure of re-exploration with periaortic lymphatic cauterization and drainage, he was treated with five cycles of retroperitoneal radiotherapy. At 12 months of follow-up, the patient remains asymptomatic without any objective evidence of chyloperitoneum relapse. Periaortic radiotherapy may be a feasible alternative in the management of the chylous ascites following abdominal aortic aneurysm surgery. PMID- 26992765 TI - Uterine trauma with fetal loss associated with chronic perforation of the inferior vena cava by an infrarenal vena cava filter. AB - Gestational complications in pregnant women have been considered a theoretical sequelae of vena cava filters (VCFs) positioned in the infrarenal segment of the inferior vena cava. We describe a 32-year-old woman who became pregnant with the known existence of an asymptomatic but chronically perforated, permanent infrarenal VCF. At 24 weeks gestation, uterine trauma leading to massive intraperitoneal hemorrhage and fetal loss occurred. Our case documents that gestational risk, heretofore theoretical, is real and calls for heightened awareness of the need for appropriate VCF management in women of childbearing age and consideration for preconception evaluation of the filter-bearing inferior vena cava in women considering pregnancy in whom VCFs have been previously implanted. PMID- 26992766 TI - Endovascular and surgical management of a cirsoid aneurysm. PMID- 26992767 TI - Renal artery to inferior vena cava fistula after nephrectomy. PMID- 26992768 TI - A systematic update on the state of novel anticoagulants and a primer on reversal and bridging. AB - BACKGROUND: Current prevention and treatment of venous thromboembolism (VTE) includes familiar agents that have been in use for many years, including unfractionated heparin, low-molecular-weight heparin (LMWH), and vitamin K antagonists (VKAs). A number of novel oral anticoagulants are currently developed or are in stages of development to either replace VKAs in concert with initial heparin or LMWH, or to replace both heparin/LMWH and VKAs totally as monotherapy. These agents hold the promise of not requiring monitoring, being safer in terms of bleeding risk than current agents, and being of equal or improved efficacy compared with established anticoagulants. METHODS: In the following report, we systematically review the oral agents currently approved or closest to approval for both VTE and atrial fibrillation treatment, focusing on the treatment of VTE: dabigatran, rivaroxaban, and apixaban. RESULTS: Findings of clinical use and comparisons to standard care of these agents are summarized in depth, by succinctly reviewing all major randomized controlled trials. Mechanistic and functional differences are reviewed, as Dabigatran targets activated factor II (factor IIa), while rivaroxaban and apixaban target activated factor X (factor Xa). We also discuss the inability at the present time to reliably reverse the anticoagulant effects of these agents, provide a suggested strategy for reversal, and finally discuss an approach to bridging these agents when other procedures are required while currently taking one of these three agents. CONCLUSIONS: These agents, while still with many unanswered questions, demonstrate great promise in the prevention and treatment of VTE. PMID- 26992770 TI - Negotiations with health insurers can lead to positive changes in policies toward venous disease. AB - Many health insurance plan (HIP) policies toward the treatment of chronic venous insufficiency (CVI) are outdated, formulated by administrators with the advice of physicians unfamiliar with CVI, and are not evidence-based. Denial of appropriate care by the HIP is frustrating to both the patient and provider, leading to delays in care and much time and effort in the appeals process. This led to meeting with the HIPs outlining the problems with their CVI policies. Through education of the HIP medical staff and reviewers, the specialists were then asked to review the policies and recommend changes. As a result of the collegial communications with the HIPs, a number of changes were made in their documents regarding treatment of CVI. These include (1) proper nomenclature for the venous systems, (2) the elimination of the need for chronic analgesic medication, (3) treatment for nonaxial varicose veins, (4) decrease in the required length of conservative (ie, elastic compression stockings) treatment prior to surgery from 12 weeks to 6 weeks, among other changes as well. While HIPs seek to reduce expenses and maximize operating margins, they are also tasked with facilitating appropriate access to necessary medical care for their members. Cooperation among physicians can lead to a dialogue between payers and providers, and can lead to positive changes in HIP policies toward the treatment of venous disease. PMID- 26992769 TI - Complications of endovenous ablation in randomized controlled trials. AB - BACKGROUND: Endovenous ablation (EVA) of the great saphenous vein (GSV), with radiofrequency (RFA) or laser ablation (EVLA), has largely replaced the standard ligation and stripping (L&S). Several randomized controlled trials (RCTs) have reported data on efficacy of the ablation with little focus on complications. We analyzed the current literature for short-term complications of EVA as compared with L&S. METHODS: We searched MEDLINE, the Cochrane Central Trials Registry, and individual journals from January 2008 through January 8, 2013 for RCTs comparing RFA and/or EVLA and/or L&S to treat GSV incompetence. We excluded studies using foam sclerotherapy, re-do GSV surgery, or the addition of a high GSV ligation to an EVA procedure. We meta-analysized short-term (<1 year) complications using the Peto odds ratio to elucidate differences between RFA (using the VNUS ClosureFAST catheter; VNUS Medical Technologies, Inc, San Jose, Calif), EVLA, and L&S. RESULTS: Seventeen RCTs met inclusion criteria. There were 317 patients who underwent RFA with ClosureFAST, 1057 patients who had EVLA, and 975 who had L&S. Seventy percent were female with a mean age of 47.5 years. The majority had CEAP clinical class 2 or 3. There was an overall complication rate of 39.6% in the 2624 limbs analyzed over all procedures. There was no evidence of a difference in the rates of venous thromboembolism. There was a significantly higher rate of wound infection for L&S (2.3%; 95% confidence interval [CI], 1.3%-3.1%) vs EVLA (0.5%; 95% CI, 0.3%-1.3%; P = .006), but not between L&S and RFA (1.5%; 95% CI, 0.4%-3.0%; P = .094). The paresthesia rate was significantly lower with EVLA (3.8%; 95% CI, 2.4%-4.5%) as compared with RFA (5.2%; 95% CI, 3.1%-7.9%; P < .001) and L&S (7.4%; 95% CI, 5.3%-8.3%; P < .001). The rate of thrombophlebitis was significantly lower for L&S (3.0%; 95% CI, 2.9%-4.0%) as compared with RFA (5.5%; 95% CI, 3.0%-7.8%; P = .003) and EVLA (5.6%; 95% CI, 4.2%-7.0%; P = .003). There was no difference in the rate of thermal skin burns between RFA and EVLA. CONCLUSIONS: Endovenous ablation and ligation and stripping of the GSV are not without complications, although usually minor. L&S has a higher wound infection rate and a lower thrombophlebitis rate as compared with EVA. EVLA has a significantly lower rate of paresthesia as compared with RFA and L&S. Thermal skin burns occur with equal frequency in RFA and EVLA. PMID- 26992772 TI - Information for Readers. PMID- 26992773 TI - Events of Interest. PMID- 26992774 TI - Risk of stroke and transient ischaemic attack after herpes zoster. AB - We assessed the association of herpes zoster (HZ) with stroke/transient ischaemic attack (TIA) in the general population according to age with controlling risk factors for stroke, using a nationwide representative cohort. The study was based on a prospective dynamic cohort consisting of 1 million Koreans representing all age groups, genders and geographical areas in the Korea Health Insurance Database. New events of stroke/TIA and HZ were identified using the diagnostic codes in the International Classification of Diseases, tenth revision. The risk for stroke/TIA after HZ was compared with HZ-free stroke/TIA individuals according to age group. A total of 766 179 adults were followed up for 11 years from 2003. The incidence of the first-diagnosed HZ cases was 9.40 per 1000 person years, and that of the first-diagnosed stroke/TIA cases was 9.77 per 1000 person years. The risk for stroke/TIA was higher in patients who had previous HZ episodes than in those who had never experienced HZ (incidence rate ratio 1.90; 95% CI 1.85-1.95). In addition, this risk persisted for several years after HZ. The risk of stroke/TIA after HZ gradually decreased with age; adjusted hazard ratio (HR) 2.04 in 18- to 30-year-olds, HR 1.74 in 30- to 40-year-olds, HR 1.43 in 40- to 50-year-olds, HR 1.23 in 50- to 60-year-olds, HR 1.24 in 60- to 70-year olds, and HR 1.29 in those >70 years old, after controlling risk factors for stroke/TIA. Our findings provide evidence that HZ carries an increased risk of stroke or TIA and that the effect of HZ on stroke decreases with increasing age. PMID- 26992776 TI - Men gain more disability-free years in older age than women, US study finds. PMID- 26992775 TI - Surgical treatment for childhood obstructive sleep apnoea: Cold-knife tonsillar dissection versus bipolar radiofrequency thermal ablation. AB - INTRODUCTION AND OBJECTIVE: Adenotonsillectomy for treatment of childhood obstructive sleep apnoea is effective. The uncomfortable postoperative period and possible complications have significantly increased the use of partial techniques, seeking to improve these aspects while achieving the same results in resolving sleep apnoea. The aim was to present the experience with 2 consecutive groups of patients, comparing total tonsillectomy to bipolar radiofrequency ablation (RFA). METHOD: A group of 96 children that underwent total tonsilloadenoidectomy using cold dissection were compared to another group of 101 children that underwent RFA. In all cases, polysomnography was performed before and 1 year after surgery. The percentage of cases with persistent disease (apnea hypopnea index >= 3) and the improvement of clinical symptoms at one year were evaluated. The percentages of surgical and anaesthetic complications in both groups were also compared. RESULT: The persistence of the syndrome was comparable in both groups: 25% in the cold dissection and 22.77% in the radiofrequency ablation group. Anaesthetic complications (5% in the group where cold dissection was used and 4.2% in the radiofrequency ablation group) and postoperative bleeding rates were very low and statistically comparable with both techniques. CONCLUSION: In the treatment of childhood obstructive sleep apnoea syndrome, both extracapsular surgery using cold scalpel and bipolar radiofrequency tunnelling techniques are safe. Likewise, results as to resolution of the syndrome show no statistically significant differences. PMID- 26992777 TI - Heme oxygenase-1 (HO-1) protects human lens epithelial cells (SRA01/04) against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis. AB - OBJECTIVES: This study aimed to investigate the protective role of heme oxygenase 1 (HO-1) in H2O2-induced oxidative stress and apoptosis in human lens epithelial cells (hLEC; SRA01/04). METHODS: SRA01/04 cells were exposed to a hydrogen peroxide (H2O2) concentration gradient and inducers of HO-1 such as cobalt protoporphyrin (CoPP) and zinc protoporphyrin (ZnPP), respectively. In addition, an RNA silencing experiment was conducted to investigate the HO-1 function in this study. A Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Western blot and ELISA were used to detect the level of HO-1 expression. In our study, hLECs were exposed to 400 MUM hydrogen peroxide (H2O2) for 24 h with or without pretreatment with 10MUMU CoPP or 10MUMU ZnPP, respectively. Double immunofluorescence staining was used for cell identification and the qualitative expression of HO-1. Expression of HO-1 was monitored using Western blot and ELISA. Intracellular reactive oxygen species (ROS) were detected by flow cytometry analyses; commercial enzymatic kits were used to measure the levels of glutathione (GSH), as well as superoxide dismutase (SOD). The proportion of cell apoptosis was quantified by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The expression of caspase family (-8, -3) proteins was measured by Western blot analysis. RESULTS: HO-1 significantly restored the cell viability under H2O2 injury via reducing the generation of ROS and increasing the levels of SOD and GSH activity. Moreover, HO 1 also inhibited H2O2-induced caspase-8 and caspase-3 proteins, thus significantly reducing the apoptosis of SRA01/04. An RNA silencing experiment demonstrated the increased resistance of LECs to oxidative stress specifically for increased levels of HO-1. CONCLUSIONS: These findings suggested that HO-1 protects human lens epithelial cells from H2O2-induced oxidant stress by upregulating antioxidant enzyme activity, reducing ROS generation, and thus inhibiting caspase family-dependent apoptosis. PMID- 26992778 TI - Molecular insights on the effect of TGF-beta1/-beta3 in human corneal fibroblasts. AB - Transforming growth factor beta (TGF-beta) plays a critical role in wound healing and the pathogenesis of fibrosis (scarring). Three isoforms of TGF-beta have been identified in mammals. Previous studies have shown that the addition of TGF-beta1 (T1) or -beta2 (T2) to human corneal fibroblasts (HCF) cultured in a 3 dimensional construct resulted in a fibrotic matrix, while the addition of TGF beta3 (T3) resulted in the production of enhanced non-fibrotic matrix as compared to control (Vitamin C [VitC] only). In the current investigation, we undertook the molecular comparison of fibrosis-related gene expression in T1 or T3-treated HCF to gain further insights into the regulation and roles of these two isoforms on the fibrotic response. HCF were cultured in 100 mm dishes in basic medium (Eagles minimum essential medium [EMEM] with 10% fetal bovine serum [FBS]). At 70 80% confluency, cells were exposed to basic medium with 0.5 mM 2-O-alpha-d glucopyranosyl-l-ascorbic acid (VitC) +/- 2 ng/ml of T1 or T3. After 4 h or 3 days, cells were harvested, and mRNA or protein was isolated. Fibrosis related mRNA levels were assayed using a commercial qRT-PCR Array. Selected proteins were examined using Western blotting (WB). Experiments were performed 6 times for the qRT-PCR and 4 times for WB for each condition. qRT-PCR results showed that most of the fibrosis-related genes were up or downregulated in HCF exposed to T1 or T3 as compared with VitC control. At 4 h, only Smad7 expression was significantly altered in T3-treated HCF, compared to T1, and at 3 days, five genes were altered. WB confirmed that T1 significantly decreased Smad7 expression compared to T3 and control, and that the expression of thrombospondin-1 in T3-stimulated HCF was enhanced compared to T1-treated cells. Finally, both T1 and T3 decreased Smad3 expression dramatically at both time points. At early time points, T1 and T3 have similar effects on expression of fibrosis related genes; however, with a longer exposure, an increasing number of genes were differentially expressed. Interestingly, most of the differentially expressed gene products are secreted by the cells and may be related to the modulation of extracellular matrix. PMID- 26992781 TI - Molecular genetics of cone-rod dystrophy in Chinese patients: New data from 61 probands and mutation overview of 163 probands. AB - Cone-rod dystrophy (CORD) is a common form of inherited retinal degeneration. Previously, we have conducted serial mutational analysis in probands with CORD either by Sanger sequencing or whole exome sequencing (WES). In the current study, variants in all genes from RetNet were selected from the whole exome sequencing data of 108 CORD probands (including 61 probands reported here for the first time) and were analyzed by multistep bioinformatics analysis, followed by Sanger sequencing and segregation validation. Data from the previous studies and new data from this study (163 probands in total) were summarized to provide an overview of the molecular genetics of CORD. The following potentially pathogenic mutations were identified in 93 of the 163 (57.1%) probands: CNGA3 (32.5%), ABCA4 (3.8%), ALMS1 (3.1%), GUCY2D (3.1%), CACNA1F (2.5%), CRX (1.8%), PDE6C (1.8%), CNGB3 (1.8%), GUCA1A (1.2%), UNC119 (0.6%), RPGRIP1 (1.2%), RDH12 (0.6%), KCNV2 (0.6%), C21orf2 (0.6%), CEP290 (0.6%), USH2A (0.6%) and SNRNP200 (0.6%). The 17 genes with mutations included 12 known CORD genes and five genes (ALMS1, RDH12, CEP290, USH2A, and SNRNP200) associated with other forms of retinal degeneration. Mutations in CNGA3 is most common in this cohort. This is a systematic molecular genetic analysis of Chinese patients with CORD. PMID- 26992779 TI - Systems biology of lens development: A paradigm for disease gene discovery in the eye. AB - Over the past several decades, the biology of the developing lens has been investigated using molecular genetics-based approaches in various vertebrate model systems. These efforts, involving target gene knockouts or knockdowns, have led to major advances in our understanding of lens morphogenesis and the pathological basis of cataracts, as well as of other lens related eye defects. In particular, we now have a functional understanding of regulators such as Pax6, Six3, Sox2, Oct1 (Pou2f1), Meis1, Pnox1, Zeb2 (Sip1), Mab21l1, Foxe3, Tfap2a (Ap2 alpha), Pitx3, Sox11, Prox1, Sox1, c-Maf, Mafg, Mafk, Hsf4, Fgfrs, Bmp7, and Tdrd7 in this tissue. However, whether these individual regulators interact or their targets overlap, and the significance of such interactions during lens morphogenesis, is not well defined. The arrival of high-throughput approaches for gene expression profiling (microarrays, RNA-sequencing (RNA-seq), etc.), which can be coupled with chromatin immunoprecipitation (ChIP) or RNA immunoprecipitation (RIP) assays, along with improved computational resources and publically available datasets (e.g. those containing comprehensive protein protein, protein-DNA information), presents new opportunities to advance our understanding of the lens tissue on a global systems level. Such systems-level knowledge will lead to the derivation of the underlying lens gene regulatory network (GRN), defined as a circuit map of the regulator-target interactions functional in lens development, which can be applied to expedite cataract gene discovery. In this review, we cover the various systems-level approaches such as microarrays, RNA-seq, and ChIP that are already being applied to lens studies and discuss strategies for assembling and interpreting these vast amounts of high throughput information for effective dispersion to the scientific community. In particular, we discuss strategies for effective interpretation of this new information in the context of the rich knowledge obtained through the application of traditional single-gene focused experiments on the lens. Finally, we discuss our vision for integrating these diverse high-throughput datasets in a single web based user-friendly tool iSyTE (integrated Systems Tool for Eye gene discovery) - a resource that is already proving effective in the identification and characterization of genes linked to lens development and cataract. We anticipate that application of a similar approach to other ocular tissues such as the retina and the cornea, and even other organ systems, will significantly impact disease gene discovery. PMID- 26992783 TI - The pros and cons of the fourth revision of thalassaemia screening programme in Iran. AB - Objective To evaluate the repercussions of recent changes to the cut-offs used in the first screening step of the pre-marital screening programme for thalassaemia prevention in Iran. Methods The profiles of 984 subjects referred to a genetic laboratory, and the tests of 242 parents of children with thalassaemia major were assessed for red blood cell (RBC) indices, haemoglobin (Hb) A2 levels and results of Hb electrophoresis. Results Of 407 suspected thalassaemia minor (STM) cases, 18 proved positive for thalassaemia minor on molecular analysis (18/407, confidence interval 2.6-6.9%). If the revised screening cut-offs had been used to determine who would undergo molecular analysis, two of these cases would not have been identified. Only 4.4% of suspected cases with lower than normal RBC indices (mean corpuscular volume <80 fl and mean corpuscular Hb <27 pg) and HbA2 (<3.5%) were diagnosed with thalassaemia minor. Conclusion The thalassaemia major prevention programme is performed in two separate steps. One step involves the screening of subjects and identification of beta-thalassaemia minor, suspected cases for thalassaemia minor (STM), and normal subject groups. The other step concerns the identification of thalassaemia minor in the STM group. Changing the cut-offs at the first screening step does not result in significant improvement from an economic view, and is associated with significant risk at the second screening step. PMID- 26992782 TI - Zisland Explorer: detect genomic islands by combining homogeneity and heterogeneity properties. AB - Genomic islands are genomic fragments of alien origin in bacterial and archaeal genomes, usually involved in symbiosis or pathogenesis. In this work, we described Zisland Explorer, a novel tool to predict genomic islands based on the segmental cumulative GC profile. Zisland Explorer was designed with a novel strategy, as well as a combination of the homogeneity and heterogeneity of genomic sequences. While the sequence homogeneity reflects the composition consistence within each island, the heterogeneity measures the composition bias between an island and the core genome. The performance of Zisland Explorer was evaluated on the data sets of 11 different organisms. Our results suggested that the true-positive rate (TPR) of Zisland Explorer was at least 10.3% higher than that of four other widely used tools. On the other hand, the new tool did not lose overall accuracy with the improvement in the TPR and showed better equilibrium among various evaluation indexes. Also, Zisland Explorer showed better accuracy in the prediction of experimental island data. Overall, the tool provides an alternative solution over other tools, which expands the field of island prediction and offers a supplement to increase the performance of the distinct predicting strategy. We have provided a web service as well as a graphical user interface and open-source code across multiple platforms for Zisland Explorer, which is available at http://cefg.uestc.edu.cn/Zisland_Explorer/ or http://tubic.tju.edu.cn/Zisland_Explorer/. PMID- 26992785 TI - Demyelinating CNS Lesions in a Teenager. PMID- 26992780 TI - The cause and consequence of fiber cell compaction in the vertebrate lens. AB - Fiber cells of the ocular lens are arranged in a series of concentric shells. New growth shells are added continuously to the lens surface and, as a consequence, the preexisting shells are buried. To focus light, the refractive index of the lens cytoplasm must exceed that of the surrounding aqueous and vitreous humors, and to that end, lens cells synthesize high concentrations of soluble proteins, the crystallins. To correct for spherical aberration, it is necessary that the crystallin concentration varies from shell-to-shell, such that cellular protein content is greatest in the center of the lens. The radial variation in protein content underlies the critical gradient index (GRIN) structure of the lens. Only the outermost shells of lens fibers contain the cellular machinery necessary for protein synthesis. It is likely, therefore, that the GRIN (which spans the synthetically inactive, organelle-free zone of the lens) does not result from increased levels of protein synthesis in the core of the lens but is instead generated through loss of volume by inner fiber cells. Because volume is lost primarily in the form of cell water, the residual proteins in the central lens fibers can be concentrated to levels of >500 mg/ml. In this short review, we describe the process of fiber cell compaction, its relationship to lens growth and GRIN formation, and offer some thoughts on the likely nature of the underlying mechanism. PMID- 26992784 TI - Comparison of High-Dose Versus Standard Dose Oseltamivir in Critically Ill Patients With Influenza. AB - BACKGROUND: Limited data support high-dose oseltamivir in critically ill patients with influenza. In several recent influenza seasons, there were oseltamivir drug shortages. METHODS: This was a retrospective cohort analysis of 57 patients admitted to the intensive care unit (ICU) with confirmed influenza. Patients receiving high-dose oseltamivir were compared to those receiving standard dosing. RESULTS: When adjusted for clinically relevant predictors of disease severity, including age, duration of therapy, Acute Physiology and Chronic Health Evaluation II score, and receipt of extracorporeal membrane oxygenation, there was no difference in the duration of mechanical ventilation, oxygenation, ICU length of stay, or hospital length of stay between the high-dose and standard dose groups. CONCLUSIONS: As compared to the standard doses of oseltamivir, higher-dose (ie, double dose) oseltamivir was not associated with improvement in any clinical outcomes. Using higher doses empirically on all patients during influenza season may exacerbate local drug shortages. PMID- 26992786 TI - Enhanced catalysis of L-asparaginase from Bacillus licheniformis by a rational redesign. AB - L-Asparaginase (3.5.1.1) being antineoplastic in nature are used in the treatment of acute lymphoblastic leukemia (ALL). However glutaminase activity is the cause of various side effects when used as a drug against acute lymphoblastic leukemia (ALL). Therefore, there is a need of a novel L-asparaginase (L-ASNase) with low or no glutaminase activity. Such a property has been observed with L-ASNase from B. licheniformis (BliA). The enzyme being glutaminase free in nature paved the way for its improvement to achieve properties similar to or near to the commercially available L-ASNases. Rational enzyme engineering approach resulted in four mutants: G238N, E232A, D103V and Q112H. Among these the mutant enzyme, D103V, had a specific activity of 597.7IU/mg, which is higher than native (rBliA) (407.65IU/mg). Moreover, when the optimum temperature and in vitro half life were studied and compared with native BliA, D103V mutant BliA was better, showing tolerance to higher temperatures and a 3 fold higher half life. Kinetic studies revealed that the mutant D103V L-ASNase has increased substrate affinity, with Km value of 0.42mM and Vmax of 2778.9MUmolmin(-1). PMID- 26992787 TI - An unusual chimeric amylosucrase generated by domain-swapping mutagenesis. AB - Amylosucrase (ASase; EC 2.4.1.4) synthesizes alpha-1,4-glucans using sucrose as a sole substrate. The aim of this study was to compare the enzymatic properties of four recombinant ASase genes to determine the underlying mechanisms thereof. Following cloning and expression in Escherichia coli, we determined that the ASase enzyme from Deinococcus geothermalis (DGAS) had the highest thermostability whereas ASase from Neisseria polysaccharea (NPAS) showed the greatest polymerization activity. Chimeric ASases were constructed using dgas and npas genes by overlap extension polymerase chain reaction. Two of the six chimeric ASases generated, NPAS-B' and DGAS-B, showed ASase activity using sucrose as the sole substrate. However, DGAS-B was not able to produce longer alpha-1,4-glucans; the highest degree of polymerization was <12. In the kinetic study, not only the substrate binding affinity but also the production rate of DGAS-B was greater than those of DGAS. Molecular dynamic computational simulation suggested that DGAS-B could not synthesize longer glucan chains because of the change in flexibilities of loops 4, 7, and 8as compared to those of DGAS. PMID- 26992788 TI - Proposed ionic bond between Arg300 and Glu270 and Glu271 are not involved in inactivation of a mutant firefly luciferase (LRR). AB - The weakness of firefly luciferase is its rapid inactivation. Many studies have been done to develop thermostable luciferases. One of these modifications was LRR mutant in which the Leu300 was substituted with Arg in the E(354)RR(356)Lampyris turkestanicus luciferase as template. LRR was more thermostable than the wild type but with only 0.02% activity. In this study, site-directed mutagenesis was used to change the proposed ionic bond between the Arg and two neighboring residues (Glu270 and Glu271), to understand if the induced interactions were responsible for inactivation in LRR. Our results showed that substitution of Glu270 and 271 with Ala removed the interactions but the activity of enzyme did not return. The E270A mutant was more active than LRR but the E271A and E270A/E271A mutants were inactive. Fluorescence and CD measurements showed that these mutations were accompanied by conformational changes. Extrinsic fluorescence measurement and obtained quenching data by KI and acrylamide also confirmed that the mutants were less compact than the LRR enzyme. In conclusion, in LRR, the interactions between Arg300 and Glu270 and Glu271 were not responsible for the enzyme inactivation and it is proposed that the enzyme inactivation is due to conformational changes of LRR mutant of firefly luciferase. PMID- 26992790 TI - Enhanced bioconversion rate and released substrate inhibition in (R) phenylephrine whole-cell bioconversion via partial acetone treatment. AB - An approach was developed to enhance the efficiency for the bioconversion of 1-(3 hydroxyphenyl)-2-(methyamino)-ethanone to (R)-phenylephrine. The strain Serratia marcescens N10612, giving the benefit of 99% enantiomeric excess in (R)-PE conversion, was used. The fermentation was devised to harvest cells with high hydrophobic prodigiosin content inside the cells. Then, the partial acetone extraction was applied to remove prodigiosin from the cells. The treatment was found to increase the cells conversion rate without loss of the cells NADPH redox system. When using 50% (v/v) acetone for 5min, the processed cells can give a specific conversion rate of 16.03MUmol/h/g-cells. As compared the treated cells with cells under the basal medium, the maximum reaction rate (Vmax) increased from 6.69 to 10.27 (MUmol/h/g-cells), the dissociation constant (Km) decreased from 0.236 to 0.167mM and the substrate inhibition constant (KSi) increased from 0.073 to 1.521mM. The 20-fold increase in substrate inhibition constant referred to a great release from the substrate inhibition for the use of S. marcescens N10612 in the bioconversion, which would greatly benefit the bioconversion to be industrialized. PMID- 26992789 TI - Towards complete hydrolysis of soy flour carbohydrates by enzyme mixtures for protein enrichment: A modeling approach. AB - Soy protein is a well-known nutritional supplement in proteinaceous food and animal feed. However, soybeans contain complex carbohydrate. Selective carbohydrate removal by enzymes could increase the protein content and remove the indigestibility of soy products for inclusion in animal feed. Complete hydrolysis of soy flour carbohydrates is challenging due to the presence of proteins and different types of non-structural polysaccharides. This study is designed to guide complex enzyme mixture required for hydrolysis of all types of soy flour carbohydrates. Enzyme broths from Aspergillus niger, Aspergillus aculeatus and Trichoderma reesei fermentations were evaluated in this study for soy carbohydrate hydrolysis. The resultant hydrolysate was measured for solubilized carbohydrate by both total carbohydrate and reducing sugar analyses. Conversion data attained after 48h hydrolysis were first fitted with models to determine the maximum fractions of carbohydrate hydrolyzable by each enzyme group, i.e., cellulase, xylanase, pectinase and alpha-galactosidase. Kinetic models were then developed to describe the increasing conversions over time under different enzyme activities and process conditions. The models showed high fidelity in predicting soy carbohydrate hydrolysis over broad ranges of soy flour loading (5-25%) and enzyme activities: per g soy flour, cellulase, 0.04-30 FPU; xylanase, 3.5-618U; pectinase, 0.03-120U; and alpha-galactosidase, 0.01-60U. The models are valuable in guiding the development and production of optimal enzyme mixtures toward hydrolysis of all types of carbohydrates present in soy flour and in optimizing the design and operation of hydrolysis reactor and process. PMID- 26992791 TI - Dihydroxyacetone production in an engineered Escherichia coli through expression of Corynebacterium glutamicum dihydroxyacetone phosphate dephosphorylase. AB - Dihydroxyacetone (DHA) has several industrial applications such as a tanning agent in tanning lotions in the cosmetic industry; its production via microbial fermentation would present a more sustainable option for the future. Here we genetically engineered Escherichia coli (E. coli) for DHA production from glucose. Deletion of E. coli triose phosphate isomerase (tpiA) gene was carried out to accumulate dihydroxyacetone phosphate (DHAP), for use as the main intermediate or precursor for DHA production. The accumulated DHAP was then converted to DHA through the heterologous expression of Corynebacterium glutamicum DHAP dephosphorylase (cghdpA) gene. To conserve DHAP exclusively for DHA production we removed methylglyoxal synthase (mgsA) gene in the DeltatpiA strain. This drastically improved DHA production from 0.83g/l (0.06g DHA/g glucose) in the DeltatpiA strain bearing cghdpA to 5.84g/l (0.41g DHA/g glucose) in the DeltatpiADeltamgsA double mutant containing the same gene. To limit the conversion of intracellular DHA to glycerol, glycerol dehydrogenase (gldA) gene was further knocked out resulting in a DeltatpiADeltamgsADeltagldA triple mutant. This triple mutant expressing the cghdpA gene produced 6.60g/l of DHA at 87% of the maximum theoretical yield. In summary, we demonstrated an efficient system for DHA production in genetically engineered E. coli strain. PMID- 26992792 TI - Modifying the endogenous electron fluxes of Rhodobacter sphaeroides 2.4.1 for improved electricity generation. AB - The purple bacteria Rhodobacter sphaeroides serve as a promising biocatalyst in the photo-microbial fuel cell system (photo-MFC). This gram-negative species performs highly efficient anoxygenic photosynthesis that ensures an anaerobic environment in the anode compartment. Previous studies incorporating R. sphaeroides into photo-MFC were conducted using platinum as the anode electrode. In this study, we detected a steady current generation of R. sphaeroides in a bioelectrochemical system where glassy carbon was the working electrode and a typical growth medium was the electrolyte. The bioelectricity generation synchronized with the supplementation of reduced carbon source and showed immediate response to illumination, which strongly indicated the correlation between the observed current and the cytoplasmic quinone activity. Modifications of the endogenous electron flows mediated by quinone pool are shown to have significantly enhanced the bioelectricity generation. We anticipate that the findings in this study would advance future optimization of R. sphaeroides as an anode strain, as well as facilitate the study of bioenergetics in photosynthetic bacteria. PMID- 26992794 TI - Obtaining a mutant of Bacillus amyloliquefaciens xylanase A with improved catalytic activity by directed evolution. AB - This study aimed to obtain xylanase exhibiting improved enzyme properties to satisfy the requirements for industrial applications. The baxA gene encoding Bacillus amyloliquefaciens xylanase A was mutated by error-prone touchdown PCR. The mutant, pCbaxA50, was screened from the mutant library by using the 96-well plate high-throughput screening method. Sequence alignment revealed the identical mutation point S138T in xylanase (reBaxA50) produced by the pCbaxA50. The specific activity of the purified reBaxA50 was 9.38U/mg, which was 3.5 times higher than that of its parent expressed in Escherichia coli BL21 (DE3), named reBaxA. The optimum temperature of reBaxA and reBaxA50 were 55 degrees C and 50 degrees C, respectively. The optimum pH of reBaxA and reBaxA50 were pH 6 and pH 5, respectively. Moreover, reBaxA50 was more stable than reBaxA under thermal and extreme pH treatment. The half-life at 60 degrees C and apparent melting temperature of reBaxA50 were 9.74min and 89.15 degrees C, respectively. High performance liquid chromatography showed that reBaxA50 released xylooligosaccharides from oat spelt, birchwood, and beechwood xylans, with xylotriose as the major product; beechwood xylan was also the most thoroughly hydrolyzed. This study demonstrated that the S138T mutation possibly improved the catalytic activity and thermostability of reBaxA50. PMID- 26992793 TI - Improving the activity of the endoglucanase, Cel8M from Escherichia coli by error prone PCR. AB - Endoglucanase is a key enzyme involved in cellulose hydrolysis and can be used in multiple industrial fields. In this study, we used error-prone PCR to engineer the endoglucanase, Cel8M, from Escherichia coli. The Cel8M belongs to the glycoside hydrolase family 8 and shows 99% identity with the reported endoglucanase from E. coli K12. Through screening of approximately 10,000Cel8M variants, two variants, Cel8ME15 and Cel8ME18, respectively showing 1.42 fold and 1.61 fold increased activities, were obtained. Through sequence analysis, it was found that Cel8ME15 had two mutations, with the residues Ala9 and Glu353 respectively substituting the residues Val9 and Lys353 of Cel8M; while Cel8ME18 had one mutation with the residue Ser117 replacing the residue Gly117 of Cel8M. Based on the analysis of the predicted 3D structure of Cel8M, it was suggested that changes of K353E and G117S might directly affect the substrate binding affinity and therefore contribute to the improved activities of Cel8ME15 and Cel8ME18. Based on all the results we had, it is believed that this study should provide a useful reference for the future engineering of other endoglucanases from glycoside hydrolase family 8. PMID- 26992795 TI - Functional and structural analyses of a 1,4-beta-endoglucanase from Ganoderma lucidum. AB - Ganoderma lucidum is a saprotrophic white-rot fungus which contains a rich set of cellulolytic enzymes. Here, we screened an array of potential 1,4-beta endoglucanases from G. lucidum based on the gene annotation library and found that one candidate gene, GlCel5A, exhibits CMC-hydrolyzing activity. The recombinant GlCel5A protein expressed in Pichia pastoris is able to hydrolyze CMC and beta-glucan but not xylan and mannan. The enzyme exhibits optimal activity at 60 degrees C and pH 3-4, and retained 50% activity at 80 and 90 degrees C for at least 15 and 10min. The crystal structure of GlCel5A and its complex with cellobiose, solved at 2.7 and 2.86A resolution, shows a classical (beta/alpha)8 TIM-barrel fold as seen in other members of glycoside hydrolase family 5. The complex structure contains a cellobiose molecule in the +1 and +2 subsites, and reveals the interactions with the positive sites of the enzyme. Collectively, the present work provides the first comprehensive characterization of an endoglucanase from G. lucidum that possesses properties for industrial applications, and strongly encourages further studying in the cellulolytic enzyme system of G. lucidum. PMID- 26992796 TI - Extracellular synthesis of silver and gold nanoparticles by Sporosarcina koreensis DC4 and their biological applications. AB - The present study highlights the microbial synthesis of silver and gold nanoparticles by Sporosarcina koreensis DC4 strain, in an efficient way. The synthesized nanoparticles were characterized by ultraviolet-visible spectrophotometry, which displayed maximum absorbance at 424nm and 531nm for silver and gold nanoparticles, respectively. The spherical shape of nanoparticles was characterized by field emission transmission electron microscopy. The energy dispersive X-ray spectroscopy and elemental mapping were displayed the purity and maximum elemental distribution of silver and gold elements in the respective nanoproducts. The X-ray diffraction spectroscopy results demonstrate the crystalline nature of synthesized nanoparticles. The particle size analysis demonstrate the nanoparticles distribution with respect to intensity, volume and number of nanoparticles. For biological applications, the silver nanoparticles have been explored in terms of MIC and MBC against pathogenic microorganisms such as Vibrio parahaemolyticus, Escherichia coli, Salmonella enterica, Bacillus anthracis, Bacillus cereus and Staphylococcus aureus. Moreover, the silver nanoparticles in combination with commercial antibiotics, such as vancomycin, rifampicin, oleandomycin, penicillin G, novobiocin, and lincomycin have been explored for the enhancement of antibacterial activity and the obtained results showed that 3MUg concentration of silver nanoparticles sufficiently enhance the antimicrobial efficacy of commercial antibiotics against pathogenic microorganism. Furthermore, the silver nanoparticles potential has been reconnoitered for the biofilm inhibition by S. aureus, Pseudomonas aeruginosa and E. coli and the results revealed sufficient activity at 6MUg concentration. In addition, gold nanoparticles have been applied for catalytic activity, for the reduction of 4-nitrophenol to 4-aminophenol using sodium borohydride and positive results were attained. PMID- 26992797 TI - A rational design for improving the trypsin resistance of aflatoxin-detoxifizyme (ADTZ) based on molecular structure evaluation. AB - The resistance of feed enzymes against proteases is crucial in livestock farming. In this study, the trypsin resistance of aflatoxin-detoxifizyme (ADTZ) is improved. ADTZ possesses 72 lys/arg residue sites, 45 of which are scattered on the outermost layers of the molecule (RSA?25%). These 45 lys/arg sites could be target sites for trypsin hydrolysis. By considering shape-matching (including physical and secondary bond interactions) and the "induced fit-effect", we hypothesized that some of these lys/arg sites are vulnerable to trypsin. A protein-protein docking simulation method was used to avoid the massive computational requirements and to address the intricacy of selecting candidate sites, as candidate site selection is affected by space displacement. Optimal mutants (K244Q/K213C/K270T and R356E/K357T/R623C) were predicted by computational design with protein folding energy analysis and molecular dynamics simulations. A trypsin digestion assay was performed, and the mutants displayed much higher stability against trypsin hydrolysis compared to the native enzyme. Moreover, temperature- and pH-activity profiles revealed that the designed mutations did not affect the catalytic activity of the enzyme. PMID- 26992798 TI - Exploitation and characterization of three versatile amidase super family members from Delftia tsuruhatensis ZJB-05174. AB - Amidases can be assigned into two families according to their amino acid sequences. Three amidases (Dt-Amis) were mined and identified from genome of Delftia tsuruhatensis. Homology analysis demonstrated that Dt-Ami 2 and Dt-Ami 6 belonged to amidase signature (AS) family, while Dt-Ami 7 belonged to nitrilase superfamily. AS amidases were shown to hydrolyze a wide spectrum of amides. Kinetic analysis demonstrated that the extension of chain length of aliphatic amides considerably decreased the Km values, and the turnover numbers (kcat) were high with linear aliphatic amides as substrates. Dt-Ami 2 showed maximum activity near a quite alkaline pH (11.0) and exhibited opposite enantioselectivity to Dt Ami 6. Furthermore, a novel bioprocess for hydrolysis of 1 cyanocyclohexaneacetamide was developed using Dt-Ami 6 as biocatalyst, resulting in >99% conversion within 1.5h at a substrate loading of 100g/L by 0.5g/L of Escherichia coli cells. On the other hand, nitrilase superfamily amidase only hydrolyzed aliphatic amides. The Km values of Dt-Ami 7 were considerably increased with the extension of chain length of aliphatic amides. The characterized enzymes from different families showed distinct biochemical characteristics and catalytic properties, leading to a better understanding of the two super amidase family members. PMID- 26992799 TI - Methylation of flavonoids: Chemical structures, bioactivities, progress and perspectives for biotechnological production. AB - Among the natural products, flavonoids have been particularly attractive, highly studied and become one of the most important promising agent to treat cancer, oxidant stress, pathogenic bacteria, inflammations, cardio-vascular dysfunctions, etc. Despite many promising roles of flavonoids, expectations have not been fulfilled when studies were extended to the in vivo condition, particularly in humans. Instability and very low oral bioavailability of dietary flavonoids are the reasons behind this. Researches have demonstrated that the methylation of these flavonoids could increase their promise as pharmaceutical agents leading to novel applications. Methylation of the flavonoids via theirs free hydroxyl groups or C atom dramatically increases their metabolic stability and enhances the membrane transport, leading to facilitated absorption and highly increased oral bioavailability. In this paper, we concentrated on analysis of flavonoid methoxides including O- and C-methoxide derivatives in aspect of structure, bioactivities and description of almost all up-to-date O- and C methyltransferases' enzymatic characteristics. Furthermore, modern biological approaches for synthesis and production of flavonoid methoxides using metabolic engineering and synthetic biology have been focused and updated up to 2015. This review will give a handful information regarding the methylation of flavonoids, methyltransferases and biotechnological synthesis of the same. PMID- 26992800 TI - Characterization of a family B DNA polymerase from Thermococcus barophilus Ch5 and its application for long and accurate PCR. AB - The family B DNA polymerase gene from the euryarchaeon Thermococcus barophilus Ch5 (Tba5) contains an open reading frame of 6198 base pairs that encodes 2065 amino acid residues. The gene is split by three inteins that must be spliced out to form the mature DNA polymerase. A Tba5 DNA polymerase gene without inteins (genetically intein-spliced) was expressed under the control of the pET 28b(+)T7lac promoter in E. coli Rosetta 2(DE3)pLysS cells. The molecular mass of the purified Tba5 DNA polymerase was about 90kDa consistent with the 90,470Da molecular mass calculated based on the 776 amino acid sequence. The optimal pH for Tba5 DNA polymerase activity was 7.5 and the optimal temperature was 70-75 degrees C. The enzyme possessed 3'->5' exonuclease activity and was activated by magnesium ions. PCR amplification using Tba5 DNA polymerase enables high-yield for 1- to 6-kb target DNA products, while 8- to 10-kb target DNA products were amplified at low or inefficient levels. To simultaneously improve product yield and amplification fidelity, Tba5 plus DNA polymerase mixtures were constituted with various amounts of Tba5 DNA polymerase mixed with Taq DNA polymerase. The Tba5 plus DNA polymerase mixtures robustly amplified up to 25-kb lambda DNA fragments. In addition, the PCR error rate of Tba5 plus3 and Tba5 plus4 mixtures were much lower than those of wild-type Tba5 DNA polymerase, Pfu DNA polymerase, Taq DNA polymerase, and Pfu plus DNA polymerase. PMID- 26992801 TI - Ethanol/O2 biofuel cell using a biocathode consisting of laccase/ HOOC MWCNTs/polydiallyldimethylammonium chloride. AB - In the present report we focused on the substitution of metallic catalysts by biocatalysts to develop a high efficient biofuel cell. A bioanode and a biocathode were designed using ADH and laccase, respectively. Carboxylated multiwall carbon nanotubes (HOOC-MWCNTs) and polydiallyldimethylammonium chloride (PDDA) were used for immobilizing the enzymes on either polymethylene green (PMG) modified glassy carbon or graphite electrodes. In this way, an ethanol-oxygen biofuel cell was designed in which PDDA/ADH/PDDA/HOOC-MWCNTs/PMG/GC and PDDA/Lac/PDDA/HOOC-MWCNTs/PMG/Gr operated as bioanode and biocathode, respectively. In the optimized condition of O2 saturated PBS (0.1M, pH 7.5) containing 1mM ethanol and 1mM NAD(+) the open-circuit voltage reached to a plateau at 504mV based of which the power density of 3.98mWcm(-2) was obtained. PMID- 26992802 TI - Synthesis of urease hybrid nanoflowers and their enhanced catalytic properties. AB - Increasing numbers of materials have been extensively used as platforms for enzyme immobilization to enhance catalytic activity and stability. Although stability of enzyme was accomplished with immobilization approaches, activity of the most of the enzymes was declined after immobilization. Herein, we synthesize the flower shaped-hybrid nanomaterials called hybrid nanoflower (HNF) consisting of urease enzyme and copper ions (Cu(2+)) and report a mechanistic elucidation of enhancement in both activity and stability of the HNF. We demonstrated how experimental factors influence morphology of the HNF. We proved that the HNF (synthesized from 0.02mgmL(-1) urease in 10mM PBS (pH 7.4) at +4 degrees C) exhibited the highest catalytic activity of ~2000% and ~4000% when stored at +4 degrees C and RT, respectively compared to free urease. The highest stability was also achieved by this HNF by maintaining 96.3% and 90.28% of its initial activity within storage of 30 days at +4 degrees C and RT, respectively. This dramatically enhanced activity is attributed to high surface area, nanoscale-entrapped urease and favorable urease conformation of the HNF. The exceptional catalytic activity and stability properties of HNF can be taken advantage of to use it in fields of biomedicine and chemistry. PMID- 26992803 TI - What is the point of spirituality? PMID- 26992809 TI - Editorial comment. PMID- 26992810 TI - Author Reply. PMID- 26992811 TI - Author Reply. PMID- 26992813 TI - Editorial Comment. PMID- 26992812 TI - Editorial Comment. PMID- 26992814 TI - Author Reply. PMID- 26992815 TI - Curating the medical humanities curriculum: twelve tips. PMID- 26992816 TI - The value of breast MRI in high-risk patients with newly diagnosed breast cancer to exclude invasive disease in the contralateral prophylactic mastectomy: Is there a role to choose wisely patients for sentinel node biopsy? AB - The aim of this study was to evaluate the presence of clinically and mammographically occult disease using breast MRI in a cohort of cancer patients undergoing contralateral prophylactic mastectomy (CPM) and the utmost indication of axillary assessment (sentinel node biopsy (SLNB)) for this side. A retrospective review of patients with unilateral invasive breast cancer or ductal carcinoma in situ (DCIS) from institutional MRI registry data (2004-2010) was conducted. Characteristics of patients undergoing CPM with breast MRI obtained less than 6 month before surgery were evaluated. A total of 2322 consecutive patients diagnosed with DCIS or stage I to III infiltrating breast cancer underwent preoperative breast MRI. Of these, 1376 patients (59.2%) had contralateral clinical breast exam and mammography without abnormalities; and 116 patients (4.9%) underwent CPM (28 excluded patients had breast MRI more than 6 months before CPM). The mean age of the 88 patients was 49 years (range 28-76 years). Two (2.3%) DCIS identified on surgical pathology specimen were not depicted by MRI and the 5 mm T1N0 invasive cancer (1.1%) was identified on MRI. Preoperative MRI showed 95% accuracy to demonstrate absence of occult disease with negative predicted value (NPV) of 98% (95% CI: 91.64-99.64%). Occult disease was present in 3.4% of CPM. MRI accurately identified the case of invasive cancer in this cohort. The high negative predictive value suggests that MRI can be used to select patients without consideration of SLNB for the contralateral side. PMID- 26992817 TI - Ultra-small lipid-dendrimer hybrid nanoparticles as a promising strategy for antibiotic delivery: In vitro and in silico studies. AB - The purpose of this study was to explore the preparation of a new lipid-dendrimer hybrid nanoparticle (LDHN) system to effectively deliver vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) infections. Spherical LDHNs with particle size, polydispersity index and zeta potential of 52.21+/-0.22 nm, 0.105+/-0.01, and -14.2+/-1.49 mV respectively were prepared by hot stirring and ultrasonication using Compritol 888 ATO, G4 PAMAM- succinamic acid dendrimer, and Kolliphor RH-40. Vancomycin encapsulation efficiency (%) in LDHNs was almost 4.5 fold greater than in lipid-polymer hybrid nanoparticles formulated using Eudragit RS 100. Differential scanning calorimetry and Fourier transform-infrared studies confirmed the formation of LDHNs. The interactions between the drug-dendrimer complex and lipid molecules using in silico modeling revealed the molecular mechanism behind the enhanced encapsulation and stability. Vancomycin was released from LDHNs over the period of 72 h with zero order kinetics and super case II transport mechanism. The minimum inhibitory concentration (MIC) against S. aureus and MRSA were 15.62 MUg/ml and 7.81 MUg/ml respectively. Formulation showed sustained activity with MIC of 62.5 MUg/ml against S. aureus and 500 MUg/ml against MRSA at the end of 72 and 54 h period respectively. The results suggest that the LDHN system can be an effective strategy to combat resistant infections. PMID- 26992818 TI - The influence of co-formers on the dissolution rates of co-amorphous sulfamerazine/excipient systems. AB - A comprehensive study on the dissolution properties of three co-amorphous sulfamerazine/excipient systems, namely sulfamerazine/deoxycholic acid, sulfamerazine/citric acid and sulfamerazine/sodium taurocholate (SMZ/DA, SMZ/CA and SMZ/NaTC; 1:1 molar ratio), is reported. While all three co-formers stabilize the amorphous state during storage, only co-amorphization with NaTC provides a dissolution advantage over crystalline SMZ and the reasons for this were analyzed. In the case of SMZ/DA extensive gelation of DA protects the amorphous phase from crystallization upon contact with buffer, but at the same time prevents the release of SMZ into solution. Disk dissolution studies showed an improved dissolution behavior of SMZ/CA compared to crystalline SMZ. However, enhanced dissolution properties were not seen in powder dissolution testing due to poor dispersibility. Co-amorphization of SMZ and NaTC resulted in a significant increase in dissolution rate, both in powder and disk dissolution studies. PMID- 26992819 TI - In vitro evaluation of the antifungal efficacy of poloxamer 407-based formulations in an infected nail plate model. AB - The in vitro efficacy of poloxamer 407-based formulations with antifungal ciclopirox olamine has been analysed in an infected nail plate model. As artificial nail plates, keratin films made of human hair keratin and slices from bovine hooves have been utilised. Several poloxamer 407-based formulations with 1 % active ingredient indicated complete growth inhibition of the dermatophyte fungus Trichophyton rubrum after 6days of incubation. PMID- 26992821 TI - Use of micro-computed tomography for the assessment of periapical lesions in small rodents: a systematic review. AB - This systematic review aimed to evaluate the literature on the acquisition-, reconstruction- and analysis parameters of micro-computed tomography (micro-CT) for the assessment of periapical lesions in rats and mice, and to illustrate the effect of variation in these parameters. The PubMed database was searched from 2000 to January 2015 (English-language publications) for reports on the use of micro-CT to evaluate periapical lesions in rats and mice. QUADAS criteria were used to rate the quality of the studies. To illustrate the effect of variations in acquisition-, reconstruction-, and analysis parameters on images of periapical lesions, micro-CT examination of two hemi-mandibles of mice, with periapical lesions around the first molar was undertaken. Twenty-one studies were identified, which analysed periapical lesions in rats or mice using micro-CT. According to the QUADAS, no study was classified as high-, seven were classified as moderate-, and 14 as low quality. The effect of variation in parameters was that voxel size may interfere with image sharpness, reconstruction may interfere with image sharpness and contrast, and inadequate plane orientation may alter the size of the periapical lesion. Nonpersonalized ROIs resulted in areas that were not part of the periapical lesion. Changing the limits of the threshold for bone tissue visualization increased lesion size. There is no defined protocol for acquiring and analysing micro-CT images of periapical lesions in rats and mice. Furthermore, acquisition-, reconstruction- and analysis parameters are not adequately explained, which may compromise the scientific impact of the studies. PMID- 26992820 TI - Rapid spread of influenza A(H1N1)pdm09 viruses with a new set of specific mutations in the internal genes in the beginning of 2015/2016 epidemic season in Moscow and Saint Petersburg (Russian Federation). AB - A dramatic increase of influenza activity in Russia since week 3 of 2016 significantly differs from previous seasons in terms of the incidence of influenza and acute respiratory infection (ARI) and in number of lethal cases. We performed antigenic analysis of 108 and whole-genome sequencing of 77 influenza A(H1N1)pdm09 viruses from Moscow and Saint Petersburg. Most of the viruses were antigenically related to the vaccine strain. Whole-genome analysis revealed a composition of specific mutations in the internal genes (D2E and M83I in NEP, E125D in NS1, M105T in NP, Q208K in M1, and N204S in PA-X) that probably emerged before the beginning of 2015/2016 epidemic season. PMID- 26992822 TI - Prevalence of Intracranial Aneurysms in Patients with Connective Tissue Diseases: A Retrospective Study. AB - BACKGROUND AND PURPOSE: Few studies have examined the prevalence of intracranial aneurysms in connective tissue diseases such as Marfan syndrome, Ehlers-Danlos syndrome, neurofibromatosis type 1, and Loeys-Dietz syndrome. We studied the prevalence of intracranial aneurysms and other intracranial neurovascular pathologies such as arteriovenous malformations and intracranial dissections, in these 4 patient populations. MATERIALS AND METHODS: We retrospectively reviewed all patients who had a clinical diagnosis of Marfan syndrome, Ehlers-Danlos syndrome, neurofibromatosis type 1, or Loeys-Dietz syndrome who underwent MRA, CTA, and/or DSA imaging of the intracranial circulation between January 1, 2005, and January 31, 2015. The presence, location, and maximum dimensions of intracranial aneurysms were catalogued. Other neurovascular findings studied included intracranial dissections and arteriovenous fistulas and shunts. Baseline data collected included demographic characteristics (sex, age, smoking history), imaging modality, and cardiovascular comorbidities. RESULTS: The prevalence of intracranial saccular and fusiform aneurysms was as follows: 14% (8/59) among patients with Marfan syndrome, 12% (12/99) among patients with Ehlers-Danlos syndrome, 11% (5/47) among patients with neurofibromatosis type 1, and 28% (7/25) among patients with Loeys-Dietz syndrome. Intracranial dissections were found in 2 patients (3%) with Marfan syndrome and 1 patient (1%) with Ehlers-Danlos syndrome. No intracranial dissections were found in patients with neurofibromatosis type 1 or Loeys-Dietz syndrome. CONCLUSIONS: Patients with connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome, neurofibromatosis type 1, and Loeys-Dietz syndrome, have a high prevalence of intracranial aneurysms. PMID- 26992824 TI - Brain site- and transmitter-dependent actions of methamphetamine, morphine and antipsychotics. AB - While several methamphetamine- and morphine-induced psychotic states are ordinarily treated by antipsychotics, the therapeutic mechanisms of antipsychotic drugs have yet been elucidated. The present study was designed to investigate the mechanisms how antipsychotic drugs suppress the behavioral changes induced by psychoactive drugs in mice. Low to medium doses of methamphetamine produced hyperlocomotion, whereas high dose of methamphetamine induced hypolocomotion. Hyperlocomotion induced by methamphetamine was potently suppressed by clozapine and 5-HT2 receptor antagonists, but not by the intra-accumbens injection of haloperidol. On the other hand, microinjection of haloperidol into the ventrolateral striatum increased locomotor activity with high dose of methamphetamine. In contrast, morphine-induced hyperlocomotion was suppressed by systemic as well as intra-accumbens injection of haloperidol, whereas relatively resistant to clozapine, compared to its effects in the case of methamphetamine. It has been widely believed that methamphetamine-induced psychosis is an animal model of schizophrenia, which is mediated by activation of accumbal dopamine receptors. Our findings suggest that methamphetamine differentially regulate monoaminergic systems (e.g., dopaminergic vs. 5-HTnergic), and accumbal dopamine receptors are not involved in methamphetamine-induced hyperlocomotion in mice. Thus, our findings may lead to a better understanding of the therapeutic mechanisms that underlie the effects of antipsychotic drugs and behavioral effects of methamphetamine and morphine. PMID- 26992823 TI - Modeling cytoadhesion of Plasmodium falciparum-infected erythrocytes and leukocytes-common principles and distinctive features. AB - Cytoadhesion of Plasmodium falciparum-infected erythrocytes to the microvascular endothelial lining shares striking similarities to cytoadhesion of leukocytes. In both cases, adhesins are presented in structures that raise them above the cell surface. Another similarity is the enhancement of adhesion under physical force (catch bonding). Here, we review recent advances in our understanding of the molecular and biophysical mechanisms underlying cytoadherence in both cellular systems. We describe how imaging, flow chamber experiments, single-molecule measurements, and computational modeling have been used to decipher the relevant processes. We conclude that although the parasite seems to induce processes that resemble the cytoadherence of leukocytes, the mechanics of erythrocytes is such that the resulting behavior in shear flow is fundamentally different. PMID- 26992825 TI - Political conservatism predicts asymmetries in emotional scene memory. AB - Variation in political ideology has been linked to differences in attention to and processing of emotional stimuli, with stronger responses to negative versus positive stimuli (negativity bias) the more politically conservative one is. As memory is enhanced by attention, such findings predict that memory for negative versus positive stimuli should similarly be enhanced the more conservative one is. The present study tests this prediction by having participants study 120 positive, negative, and neutral scenes in preparation for a subsequent memory test. On the memory test, the same 120 scenes were presented along with 120 new scenes and participants were to respond whether a scene was old or new. Results on the memory test showed that negative scenes were more likely to be remembered than positive scenes, though, this was true only for political conservatives. That is, a larger negativity bias was found the more conservative one was. The effect was sizeable, explaining 45% of the variance across subjects in the effect of emotion. These findings demonstrate that the relationship between political ideology and asymmetries in emotion processing extend to memory and, furthermore, suggest that exploring the extent to which subject variation in interactions among emotion, attention, and memory is predicted by conservatism may provide new insights into theories of political ideology. PMID- 26992828 TI - Sox2/Oct4: A delicately balanced partnership in pluripotent stem cells and embryogenesis. AB - Considerable progress has been made in understanding the roles of Sox2 and Oct4 in embryonic stem cells and mammalian embryogenesis. Specifically, significant progress has been made in answering three questions about the functions of Sox2 and Oct4, which are the focus of this review. 1) Are the first or second cell lineage decisions during embryogenesis controlled by Oct4 and/or Sox2? 2) Do the levels of Oct4 and Sox2 need to be maintained within narrow limits to promote normal development and to sustain the self-renewal of pluripotent stem cells? 3) Do Oct4 and Sox2 work closely together or is the primary role of Sox2 in pluripotent cells to ensure the expression of Oct4? Although significant progress has been made in answering these questions, additional studies are needed to resolve several important remaining issues. Nonetheless, the preponderance of the evidence suggests there is considerable crosstalk between Sox2 and Oct4, and further suggests Sox2 and Oct4 function as molecular rheostats and utilize negative feedback loops to carefully balance their expression and other critical genes during embryogenesis. This article is part of a Special Issue entitled: The Oct transcription factor family, edited by Dr. Dean Tantin. PMID- 26992827 TI - Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude. AB - Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25MUg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude. PMID- 26992830 TI - James Cook University's decentralised medical training model: an important part of the rural workforce pipeline in northern Australia. AB - INTRODUCTION: There has been much recent investment to improve the recruitment and retention of medical graduates in rural Australia. This paper describes the different outcomes of the strategies used at the James Cook University (JCU) medical school to improve the recruitment and retention of medical graduates in northern Australian towns: the decentralised model of four rural clinical schools, selecting students with a rural home town, enrolling students under the Bonded Medical Placements (BMP) scheme, and providing rurally orientated scholarships. METHODS: Home town at application to medical school, clinical school location, scholarship, BMP and postgraduate practice location data for JCU medical graduates were retrieved from an ongoing longitudinal cohort study. Multivariate logistic regression analysis was used to identify independent predictors of intern practice location from 2006 to 2013, and current (2014) practice location for postgraduate year 4-9 graduates for each of the four rural clinical school sites of Townsville, Cairns, Darwin and Mackay. RESULTS: The strongest predictor of JCU Bachelor of Medicine, Bachelor of Surgery (MBBS) graduates undertaking their internship in Townsville, Cairns, Mackay or Darwin hospitals was attending the JCU clinical school in that location (p<0.001, prevalence odds ratios (POR)=7.1; p<0.001, POR=11.5; p<0.001, POR=19.4; p<0.001, POR=85.7; respectively). Attending the JCU clinical school in the main town was also a strong predictor of JCU MBBS graduates currently practising (2014) in the Townsville, Cairns and Mackay health service districts (p<0.001, POR=2.9; p<0.001, POR=3.8; p=0.033, POR=3.6; respectively). CONCLUSIONS: While this study supports the effectiveness of improving the rural medical workforce via the targeted selection of students with a rural background, the JCU medical school's decentralised medical education program also appears to be significantly associated with rural recruitment and retention, including in districts of workforce shortage and/or geographically remote locations. These findings support other evidence that decentralised medical training can assist recruitment to underserved regions, and have implications for other jurisdictions looking to invest in a decentralised training model. PMID- 26992829 TI - Distribution of donor lungs in the United States: a case for broader geographic sharing. AB - OBJECTIVES: To evaluate the association between allocation of donor lungs by geographic sharing type (GST) and lung allocation score (LAS). METHODS: UNOS data included lung transplant recipients between 5/4/05 and 09/30/15 (n = 17 416) grouped by GST of donor lungs: local, regional, or national. Recipients were stratified by LAS <50, 50-75, and >75. Kaplan-Meier analysis was used to assess five-yr survival. RESULTS: The majority of lungs were shared locally (n = 9200; 52.8%) followed by nationally (n = 5356; 30.8%) and regionally (n = 2860; 16.4%). There was a significant difference in the mean LAS at transplant (local: 43.7 +/- 15; regional: 49.5 +/- 18.8; national 51 +/- 19.4; p < 0.001). There was a significant association between GST and LAS (p < 0.001). The majority (n = 7431; 58.2%) of recipients with LAS <50 received local lungs. Recipients with LAS >75 received a majority of their organs from national (n = 881; 45.4%) and regional (n = 414; 21.6%) donors. Although statistically significant (p = 0.024), absolute decline in five-yr survival by GST in the national GST was only 1.1% compared to the local GST. CONCLUSIONS: Nearly half of all lungs in the United States are allocated locally to recipients with an LAS <50. Additional studies should determine if organ sharing over broader geographies would improve waitlist outcomes. PMID- 26992826 TI - Studies of mice with cyclic AMP-dependent protein kinase (PKA) defects reveal the critical role of PKA's catalytic subunits in anxiety. AB - Cyclic adenosine mono-phosphate-dependent protein kinase (PKA) is critically involved in the regulation of behavioral responses. Previous studies showed that PKA's main regulatory subunit, R1alpha, is involved in anxiety-like behaviors. The purpose of this study was to determine how the catalytic subunit, Calpha, might affect R1alpha's function and determine its effects on anxiety-related behaviors. The marble bury (MB) and elevated plus maze (EPM) tests were used to assess anxiety-like behavior and the hotplate test to assess nociception in wild type (WT) mouse, a Prkar1a heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the regulatory subunit (R1alpha), a Prkaca heterozygote (Prkaca(+/-)) mouse with haploinsufficiency for the catalytic subunit (Calpha), and a double heterozygote mouse (Prkar1a(+/-)/Prkaca(+/-)) with haploinsufficiency for both R1alpha and Calpha. We then examined specific brain nuclei involved in anxiety. Results of MB test showed a genotype effect, with increased anxiety-like behavior in Prkar1a(+/-) and Prkar1a(+/-)/Prkaca(+/-) compared to WT mice. In the EPM, Prkar1a(+/-) spent significantly less time in the open arms, while Prkaca(+/-) and Prkar1a(+/-)/Prkaca(+/-) mice displayed less exploratory behavior compared to WT mice. The loss of one Prkar1a allele was associated with a significant increase in PKA activity in the basolateral (BLA) and central (CeA) amygdala and ventromedial hypothalamus (VMH) in both Prkar1a(+/ ) and Prkar1a(+/-)/Prkaca(+/-) mice. Alterations of PKA activity induced by haploinsufficiency of its main regulatory or most important catalytic subunits result in anxiety-like behaviors. The BLA, CeA, and VMH are implicated in mediating these PKA effects in brain. PMID- 26992831 TI - Internet Vigilantism: Attitudes and Experiences of University Students Toward Cyber Crowdsourcing in Hong Kong. AB - With the development of the Internet, Internet vigilantism (netilantism) has emerged as a new phenomenon in recent years. Although there are several qualitative studies explaining netilantism, there is little empirical research on public perceptions of netilantism. This article aims to outline Hong Kong university students' general perception of netilantism and investigate the differences between different roles in netilantism. By using empowerment theory as the theoretical framework, we will investigate whether Internet vigilantes (netilantes) (a) perceive the criminal justice system as effective, (b) possess high levels of self-efficacy in the cyber world, and (c) tend to believe netilantism can achieve social justice. Findings support the proposition that human flesh search engine is an empowerment tool for the netilante enabling him or her to achieve his goal of social justice. Different roles in netilantism (i.e., bystander, netilante, victim, and none of the above roles) have different perceptions of netilantism and the criminal justice system. The results will be explained by studying two representative cases of netilantism-the "Government Official Molestation" case and the "Cat Abuse in Shun Tin Village" case from China and Hong Kong, respectively. PMID- 26992834 TI - The interaction between constituent year and within-1-year effects in elite German youth basketball. AB - The current state of research on relative age effects in basketball shows an uneven picture. These mixed results might be caused by the interaction of constituent year and within-year effects. Our aim was to examine constituent and within-1-year effects in elite German youth basketball. The sample (n = 4400) included players competing in the JBBL (Under-16 first division) and the NBBL (Under-19 first division) from 2011/2012 until 2013/2014. A multi-way frequency analysis revealed an interaction of constituent year effects and within-1-year effects for the JBBL, chi2 (6, 2590) = 12.76, P < 0.05. NBBL data showed significant constituent year effects, chi2 (2, n = 1810) = 25.32, P < 0.01, and within-1-year effects for all three age bands but no interaction. The interaction between constituent year and within-1-year effects in the JBBL showed reduced within-1-year effects with increasing age. Once players enter the system in the JBBL, relatively younger players seem less likely to drop out of the system. Results offer new insight regarding how the regulations of this talent development system may influence athletes' opportunities to enter the system and their likelihood of staying at the highest levels of competition. PMID- 26992832 TI - Development of broad-spectrum human monoclonal antibodies for rabies post exposure prophylaxis. AB - Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response. PMID- 26992835 TI - AML multi-gene panel testing: A review and comparison of two gene panels. AB - BACKGROUND/OBJECTIVE: Risk adapted therapy is standard practice in Acute Myeloid Leukemia (AML). A common diagnostic approach involves focusing on a three gene panel (CEPBA, FLT3, and NPM1). However, a complete representation of prognostic and predictive factors in AML necessitates an expanded series of genes, due to the dynamic interactions present between concurrent mutations. Hence, the current study aims to describe the benefits of an expanded risk profile in an unselected cohort of AML cases. METHODS: The genomes of 11 randomly selected patients with AML were sequenced using next generation sequencing. A narrow three gene panel and broader 50 gene panel were contrasted. RESULTS: The expanded gene panel detected one additional pathogenic mutation in five patients and two pathogenic mutations in two patients, resulting in a change in their risk profile. Only 5/11 (45%) of AML patients demonstrated a pathogenic mutation on the 3 gene profile, however all patients had at least one detectable pathogenic mutation on the broader gene panel. The detection of a concurrent mutation by the expanded gene panel reversed the favorable risk profile for three patients. CONCLUSIONS: Detection of concurrent mutations enables rejection or validation of prognoses associated with NPM1 or CEBPA mutations. DNMT3a and TP53 mutations in AML have a pertinent prognostic and therapeutic value for patients and their addition enhances the current three gene panel. In our small study, the three gene panel changed the prognosis for three patients (3/11, 27%) with the detection of commonly occurring AML mutations. PMID- 26992836 TI - In Vivo 3-Dimensional Strain Mapping of the Optic Nerve Head Following Intraocular Pressure Lowering by Trabeculectomy. AB - PURPOSE: To map the 3-dimensional (3D) strain of the optic nerve head (ONH) in vivo after intraocular pressure (IOP) lowering by trabeculectomy (TE) and to establish associations between ONH strain and retinal sensitivity. DESIGN: Observational case series. PARTICIPANTS: Nine patients with primary open-angle glaucoma (POAG) and 3 normal controls. METHODS: The ONHs of 9 subjects with POAG (pre-TE IOP: 25.3+/-13.9 mmHg; post-TE IOP: 11.8+/-8.6 mmHg) were imaged (1 eye per subject) using optical coherence tomography (OCT) (Heidelberg Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) before (<21 days) and after (<50 days) TE. The imaging protocol was repeated for 3 controls in whom IOP was not altered. In each post-TE OCT volume, 4 tissues were manually segmented (prelamina, choroid, sclera, and lamina cribrosa [LC]). For each ONH, a 3D tracking algorithm was applied to both post- and pre-TE OCT volumes to extract IOP-induced 3D displacements at segmented nodes. Displacements were filtered, smoothed, and processed to extract 3D strain relief (the amount of tissue deformation relieved after TE). Strain relief was compared with measures of retinal sensitivity from visual field testing. MAIN OUTCOME MEASURES: Three dimensional ONH displacements and strain relief. RESULTS: On average, strain relief (averaged or effective component) in the glaucoma ONHs (8.6%) due to TE was higher than that measured in the normal controls (1.07%). We found no associations between the magnitude of IOP decrease and the LC strain relief (P > 0.05), suggesting biomechanical variability across subjects. The LC displaced posteriorly, anteriorly, or not at all. Furthermore, we found linear associations between retinal sensitivity and LC effective strain relief (P < 0.001; high strain relief associated with low retinal sensitivity). CONCLUSIONS: We demonstrate that ONH displacements and strains can be measured in vivo and that TE can relieve ONH strains. Our data suggest a wide variability in ONH biomechanics in the subjects examined in this study. We further demonstrate associations between LC effective strain relief and retinal sensitivity. PMID- 26992833 TI - The dark matter of the cancer genome: aberrations in regulatory elements, untranslated regions, splice sites, non-coding RNA and synonymous mutations. AB - Cancer is a disease of the genome caused by oncogene activation and tumor suppressor gene inhibition. Deep sequencing studies including large consortia such as TCGA and ICGC identified numerous tumor-specific mutations not only in protein-coding sequences but also in non-coding sequences. Although 98% of the genome is not translated into proteins, most studies have neglected the information hidden in this "dark matter" of the genome. Malignancy-driving mutations can occur in all genetic elements outside the coding region, namely in enhancer, silencer, insulator, and promoter as well as in 5'-UTR and 3'-UTR Intron or splice site mutations can alter the splicing pattern. Moreover, cancer genomes contain mutations within non-coding RNA, such as microRNA, lncRNA, and lincRNA A synonymous mutation changes the coding region in the DNA and RNA but not the protein sequence. Importantly, oncogenes such as TERT or miR-21 as well as tumor suppressor genes such as TP53/p53, APC, BRCA1, or RB1 can be affected by these alterations. In summary, coding-independent mutations can affect gene regulation from transcription, splicing, mRNA stability to translation, and hence, this largely neglected area needs functional studies to elucidate the mechanisms underlying tumorigenesis. This review will focus on the important role and novel mechanisms of these non-coding or allegedly silent mutations in tumorigenesis. PMID- 26992837 TI - Ultra-Widefield Steering-Based Spectral-Domain Optical Coherence Tomography Imaging of the Retinal Periphery. AB - PURPOSE: To describe the spectral-domain optical coherence tomography (SD OCT) features of peripheral retinal findings using an ultra-widefield (UWF) steering technique to image the retinal periphery. DESIGN: Observational study. PARTICIPANTS: A total of 68 patients (68 eyes) with 19 peripheral retinal features. MAIN OUTCOME MEASURES: Spectral-domain OCT-based structural features. METHODS: Nineteen peripheral retinal features, including vortex vein, congenital hypertrophy of the retinal pigment epithelium, pars plana, ora serrata pearl, typical cystoid degeneration (TCD), cystic retinal tuft, meridional fold, lattice and cobblestone degeneration, retinal hole, retinal tear, rhegmatogenous retinal detachment, typical degenerative senile retinoschisis, peripheral laser coagulation scars, ora tooth, cryopexy scars (retinal tear and treated retinoblastoma scar), bone spicules, white without pressure, and peripheral drusen, were identified by peripheral clinical examination. Near-infrared scanning laser ophthalmoscopy images and SD OCT of these entities were registered to UWF color photographs. RESULTS: Spectral-domain OCT resolved structural features of all peripheral findings. Dilated hyporeflective tubular structures within the choroid were observed in the vortex vein. Loss of retinal lamination, neural retinal attenuation, retinal pigment epithelium loss, or hypertrophy was seen in several entities, including congenital hypertrophy of the retinal pigment epithelium, ora serrata pearl, TCD, cystic retinal tuft, meridional fold, lattice, and cobblestone degenerations. Hyporeflective intraretinal spaces, indicating cystoid or schitic fluid, were seen in ora serrata pearl, ora tooth, TCD, cystic retinal tuft, meridional fold, retinal hole, and typical degenerative senile retinoschisis. The vitreoretinal interface, which often consisted of lamellae-like structures of the condensed cortical vitreous near or adherent to the neural retina, appeared clearly in most peripheral findings, confirming its association with many low-risk and vision-threatening pathologies, such as lattice degeneration, meridional folds, retinal breaks, and rhegmatogenous retinal detachments. CONCLUSIONS: Ultra-widefield steering-based SD OCT imaging of the retinal periphery is feasible with current commercially available devices and provides detailed anatomic information of the peripheral retina, including benign and pathologic entities, not previously imaged. This imaging technique may deepen our structural understanding of these entities and their potentially associated macular and systemic pathologies, and may influence decision-making in clinical practice, particularly in areas with teleretinal capabilities but poor access to retinal specialists. PMID- 26992838 TI - Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). AB - BACKGROUND: The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. PATTERN OF RETINOPATHY: Although the locus of toxic damage is parafoveal in many eyes, Asian patients often show an extramacular pattern of damage. DOSE: We recommend a maximum daily HCQ use of <=5.0 mg/kg real weight, which correlates better with risk than ideal weight. There are no similar demographic data for CQ, but dose comparisons in older literature suggest using <=2.3 mg/kg real weight. RISK OF TOXICITY: The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years. However, even after 20 years, a patient without toxicity has only a 4% risk of converting in the subsequent year. MAJOR RISK FACTORS: High dose and long duration of use are the most significant risks. Other major factors are concomitant renal disease, or use of tamoxifen. SCREENING SCHEDULE: A baseline fundus examination should be performed to rule out preexisting maculopathy. Begin annual screening after 5 years for patients on acceptable doses and without major risk factors. SCREENING TESTS: The primary screening tests are automated visual fields plus spectral-domain optical coherence tomography (SD OCT). These should look beyond the central macula in Asian patients. The multifocal electroretinogram (mfERG) can provide objective corroboration for visual fields, and fundus autofluorescence (FAF) can show damage topographically. Modern screening should detect retinopathy before it is visible in the fundus. TOXICITY: Retinopathy is not reversible, and there is no present therapy. Recognition at an early stage (before any RPE loss) is important to prevent central visual loss. However, questionable test results should be repeated or validated with additional procedures to avoid unnecessary cessation of valuable medication. COUNSELING: Patients (and prescribing physicians) should be informed about risk of toxicity, proper dose levels, and the importance of regular annual screening. PMID- 26992839 TI - Clinical Evaluation and Cone Alterations in Choroideremia. PMID- 26992840 TI - Incidence of Acute Postoperative Endophthalmitis after Cataract Surgery: A Nationwide Study in France from 2005 to 2014. AB - PURPOSE: To report the incidence of acute postoperative endophthalmitis (POE) after cataract surgery from 2005 to 2014 in France. DESIGN: Cohort study. PARTICIPANTS: Patients undergoing operation for cataract surgery by phacoemulsification and presenting acute POE. METHODS: We identified acute POE occurring within 6 weeks after phacoemulsification cataract surgery and the use of intracameral antibiotic injection during the surgical procedure by means of billing codes from a national database. MAIN OUTCOME MEASURES: Incidence of acute POE. RESULTS: From January 2005 to December 2014, 6 371 242 eyes in 3 983 525 patients underwent phacoemulsification cataract surgery. The incidence of acute POE after phacoemulsification decreased from 0.145% to 0.053% during this 10-year period; the unadjusted incidence rate ratio (IRR) (95% confidence interval) was 0.37 (0.32-0.42; P < 0.001). In multivariate analysis, intracameral antibiotic injection was associated with a lower risk of acute POE 0.53 (0.50-0.57; P < 0.001), whereas intraoperative posterior capsule rupture, combined surgery, and gender (male) were associated with a higher risk of acute POE: 5.24 (4.11-6.68), 1.77 (1.53-2.05), and 1.48 (1.40-1.56) (P < 0.001), respectively. CONCLUSIONS: Access to a national database allowed us to observe a decrease in acute POE after phacoemulsification cataract surgery from 2005 to 2014. Within the same period, the use of intracameral antibiotics during the surgical procedures increased. PMID- 26992841 TI - Visual and Anatomic Outcomes in Patients with Diabetic Macular Edema with Limited Initial Anatomic Response to Ranibizumab in RIDE and RISE. AB - PURPOSE: To explore the visual acuity and anatomic outcomes over 24 months of patients with diabetic macular edema (DME) who showed a delayed anatomic response after 3 ranibizumab injections in the RIDE and RISE trials. DESIGN: Analysis of data from RIDE and RISE, 2 phase III, parallel, randomized, multicenter, double masked trials (ClinicalTrials.gov identifiers, NCT00473382 and NCT00473330). PARTICIPANTS: Patients with DME (n = 681) who received monthly intravitreal ranibizumab 0.3-mg injections, ranibizumab 0.5-mg injections, or sham injections. METHODS: Patients were separated into 3 groups: delayed responders (ranibizumab treated patients with <=10% central foveal thickness [CFT] reduction after 3 injections), immediate responders (ranibizumab-treated patients with >10% CFT reduction after 3 injections), and sham recipients. Central foveal thickness was measured by time-domain optical coherence tomography, best-corrected visual acuity (BCVA) was measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores, and diabetic retinopathy (DR) was measured by the standardized ETDRS severity scale (using fundus photographs). MAIN OUTCOME MEASURES: Month-24 CFT, BCVA, and DR severity levels. RESULTS: In RIDE and RISE, 9% to 10% of ranibizumab-treated eyes were delayed responders. At month 24, delayed responders had less CFT reduction (median, -102 MUm) from baseline compared with immediate responders (median, -274 MUm; P < 0.0001). Delayed responders gained a median of 10 letters at 24 months, similar to immediate responders (14 letters; P = 0.15). At month 24, DR improvement among the delayed responders (31% and 22% of patients with >=2- or >=3-step DR improvement, respectively) was comparable with that among immediate responders (42% and 17%, respectively; P = 0.21 and P = 0.48, respectively). CONCLUSIONS: With continued treatment, at month 24, patients with DME with delayed anatomic response (<=10% CFT reduction) after 3 ranibizumab injections had visual acuity gains and DR improvement similar to those of patients with DME who had immediate anatomic response. PMID- 26992842 TI - Gender Inequalities in Surgery for Bilateral Cataract among Children in Low Income Countries: A Systematic Review. AB - PURPOSE: Cataract is a common cause of avoidable blindness in children globally. Gender differences in service access among children are reported for several conditions, but not for surgery for bilateral cataract. In this review we compared the proportion of children undergoing surgery for bilateral, nontraumatic cataract who were girls, using data from high-income, gender-neutral countries as the reference. DESIGN: Systematic review. METHODS: A systematic review of MEDLINE was undertaken in November 2014. Studies published only from 2000 onward were included because techniques and services have improved over time. A wide range of study designs was included such as: population-based data, registers, studies of surgical techniques, clinical trials, and so forth. All articles with 20 or fewer cases were excluded or were of long-term follow-up only, because this may reflect gender differences during follow-up. A meta analysis was not planned. RESULTS: Thirty-eight studies (6854 children) were included from 1342 titles, 10 from high-income countries. Many did not present data disaggregated by gender. Overall, 36.5% of children were girls. In gender neutral countries, 47.5% of children (777/1636) were girls, being similar in the Middle East, North Africa, and Central Asia (48.6%; 87/179) and in Latin America and the Caribbean (43.7%; 188/430). Proportions were significantly lower in sub Saharan Africa (41.1%; 225/547), East Asia and the Pacific (36.0%; 237/658), and South Asia (29.1%; 991/3404). CONCLUSIONS: Access to surgery by girls with bilateral cataract is lower in some regions than by boys. Barriers to access specific to girls need to be identified, particularly in Asia, to assess interventions to improve uptake. PMID- 26992843 TI - Diagnostic Accuracy of Optical Coherence Tomography and Scanning Laser Tomography for Identifying Glaucoma in Myopic Eyes. AB - PURPOSE: Ruling out glaucoma in myopic eyes often poses a diagnostic challenge because of atypical optic disc morphology and visual field defects that can mimic glaucoma. We determined whether neuroretinal rim assessment based on Bruch's membrane opening (BMO), rather than conventional optic disc margin (DM)-based assessment or retinal nerve fiber layer (RNFL) thickness, yielded higher diagnostic accuracy in myopic patients with glaucoma. DESIGN: Case-control, cross sectional study. PARTICIPANTS: Myopic patients with glaucoma (n = 56) and myopic normal controls (n = 74). METHODS: Myopic subjects with refraction error greater than -2 diopters (D) (spherical equivalent) and typical myopic optic disc morphology, with and without glaucoma, were recruited from a glaucoma clinic and a local optometry practice. The final classification of myopic glaucoma or myopic control was based on consensus assessment by 3 clinicians of visual fields and optic disc photographs. Participants underwent imaging with confocal scanning laser tomography for measurement of DM rim area (DM-RA) and with spectral domain optical coherence tomography (SD OCT) for quantification of a BMO-based neuroretinal rim parameter, minimum rim width (BMO-MRW), and RNFL thickness. MAIN OUTCOME MEASURES: Sensitivity of DM-RA, BMO-MRW, and RNFL thickness at a fixed specificity of 90% and partial area under the curves (pAUCs) for global and sectoral parameters for specificities >=90%. RESULTS: Sensitivities at 90% specificity were 30% for DM-RA and 71% for both BMO-MRW and RNFL thickness. The pAUC was higher for the BMO-MRW compared with DM-RA (P < 0.001), but similar to RNFL thickness (P > 0.5). Sectoral values of BMO-MRW tended to have a higher, but nonsignificant, pAUC across all sectors compared with RNFL thickness. CONCLUSIONS: Bruch's membrane opening MRW is more sensitive than DM-RA and similar to RNFL thickness for the identification of glaucoma in myopic eyes and offers a valuable diagnostic tool for patients with glaucoma with myopic optic discs. PMID- 26992844 TI - 2-Dimensional graphene as a route for emergence of additional dimension nanomaterials. AB - Dimension has a different and impactful significance in the field of innovation, research and technologies. Starting from one-dimension, now, we all are moving towards 3-D visuals and try to do the things in this dimension. However, we still have some very innovative and widely applicable nanomaterials, which have tremendous potential in the form of 2-D only i.e. graphene. In this review, we have tried to incorporate the reported pathways used so far for modification of 2 D graphene sheets to make is three-dimensional. The modified graphene been applied in many fields like supercapacitors, sensors, catalysis, energy storage devices and many more. In addition, we have also incorporated the conversion of 2 D graphene to their various other dimensions like zero-, one- or three dimensional nanostructures. PMID- 26992845 TI - From macroplastic to microplastic: Degradation of high-density polyethylene, polypropylene, and polystyrene in a salt marsh habitat. AB - As part of the degradation process, it is believed that most plastic debris becomes brittle over time, fragmenting into progressively smaller particles. The smallest of these particles, known as microplastics, have been receiving increased attention because of the hazards they present to wildlife. To understand the process of plastic degradation in an intertidal salt marsh habitat, strips (15.2 cm * 2.5 cm) of high-density polyethylene, polypropylene, and extruded polystyrene were field-deployed in June 2014 and monitored for biological succession, weight, surface area, ultraviolet (UV) transmittance, and fragmentation. Subsets of strips were collected after 4 wk, 8 wk, 16 wk, and 32 wk. After 4 wk, biofilm had developed on all 3 polymers with evidence of grazing periwinkles (Littoraria irrorata). The accreting biofilm resulted in an increased weight of the polypropylene and polystyrene strips at 32 wk by 33.5% and 167.0%, respectively, with a concomitant decrease in UV transmittance by approximately 99%. Beginning at 8 wk, microplastic fragments and fibers were produced from strips of all 3 polymers, and scanning electron microscopy revealed surface erosion of the strips characterized by extensive cracking and pitting. The results suggest that the degradation of plastic debris proceeds relatively quickly in salt marshes and that surface delamination is the primary mechanism by which microplastic particles are produced in the early stages of degradation. Environ Toxicol Chem 2016;35:1632-1640. (c) 2016 SETAC. PMID- 26992846 TI - Prognostic Impact of Multiple Clinicopathologic Risk Factors and c-MET Overexpression in Patients Who Have Undergone Resection of Stage IB Non-Small Cell Lung Cancer. AB - BACKGROUND: Several studies have suggested risk factors for poor survival in stage IB non-small-cell lung cancer (NSCLC) patients. However, these factors are not definite indicators of adjuvant chemotherapy for stage IB cancer, and most of them can be used to consider adjuvant chemotherapy. We aimed to determine the clinicopathologic factors and assess whether c-MET is a prognostic factor in stage IB NSCLC patients who have undergone surgery. Additionally, we determined the relevance of the factors and the recurrence pattern in these patients. PATIENTS AND METHODS: This study included 115 patients who underwent resection of pathologic stage IB NSCLC between January 2005 and December 2013. We retrospectively reviewed the clinicopathologic data and performed immunohistochemical analysis for c-MET. Recurrence-free survival (RFS), cancer specific survival (CSS), and overall survival (OS) were evaluated according to clinicopathologic factors and c-MET expression. RESULTS: Lymphovascular invasion (LVI) and c-MET overexpression were significantly associated with poor RFS. A large tumor with visceral pleural invasion (VPI) or LVI, moderate/poor differentiation with LVI, and VPI with LVI were negative prognostic factors for RFS and CSS. c-MET overexpression with a large tumor, VPI, or LVI was an independent prognostic factor for poor RFS and CSS, and LVI was a significant factor for distant recurrence. CONCLUSION: LVI and c-MET overexpression might be associated with poor prognosis in stage IB NSCLC patients. Additionally, survival might be poor in stage IB patients with multiple pathologic risk factors. Moreover, there is a high possibility of distant recurrence in patients with LVI. PMID- 26992847 TI - Effectiveness of anti-TNFalpha drugs in patients with Crohn's disease who do not achieve remission with their first anti-TNFalpha agent. AB - BACKGROUND: Anti-TNF treatment is effective for Crohn's disease (CD); however, some patients did not achieve remission with these drugs. AIMS: To evaluate the short-term effectiveness of a second anti-TNF in CD patients who did not achieve remission with the first one and to assess its durability. METHODS: Patients who did not achieve remission with their first anti-TNF were included. The short-term response of the second anti-TNF was assessed, the long-term response was evaluated in patients who achieved remission (Kaplan-Meier). Cox-regression was performed to identify predictors of loss of efficacy. RESULTS: In all, 118 CD patients received a second anti-TNF after primary failure of the first. The first anti-TNF was discontinued because of non-response in 54% of patients and partial response in 46%. Fifty-one percent of patients achieved remission in the short term. The probability of remission was lower in patients for whom the drug indication was perianal disease (OR=0.3, 95% CI=0.1-0.7, P=0.005). The dose was increased in 33% of patients, and 37% achieved/regained remission. The probability of maintaining remission was 76%, 68% and 64% at 12, 18 and 24 months, respectively. CONCLUSIONS: Approximately half of the patients achieved remission with a second anti-TNF after primary failure of the first, this strategy was less effective in patients with perianal disease. PMID- 26992848 TI - Hepatocellular carcinoma detected by regular surveillance: Does timely confirmation of diagnosis matter? AB - BACKGROUND: Although current guidelines recommended surveillance of hepatocellular carcinoma, prognosis in patients undergoing enhanced follow-up has yet to be evaluated. AIMS: Examine outcomes of hepatocellular carcinoma diagnosed during enhanced follow-up. METHODS: During 2010-2012, 194 patients underwent ultrasonography surveillance were diagnosed with hepatocellular carcinoma and divided into: (A) immediate diagnosis (N=105, 54.1%) after positive ultrasonography, (B) enhanced follow-up: (N=38, 19.6%) for initial negative recall procedures, (C) late call back: (N=28, 14.4%) recall procedures were deferred after positive ultrasonography, and (D) beyond ultrasonography: (N=23, 11.9%) surveillance ultrasonography had been negative. RESULTS: Median time from positive ultrasonography to confirmation of hepatocellular carcinoma were 9.5 months (2-67) in the Group B and 6.5 months (3-44) in the Group C. Stage distribution and 3-year survival rates were similar amongst all Groups. Surveillance intervals longer than 6 months were associated with the non-curative stage (3.7% vs. 12.5%, p=0.04). Nine (4.6%) patients underwent surveillance were diagnosed as Barcelona-Clinic Liver Cancer stage C. CONCLUSION: Enhanced follow up by current guidelines is appropriate that treatment can be deferred until a definite diagnosis. Despite optimal surveillance interval and recall policies, few non-curative stage diagnoses seemed inevitable under current standard of care. PMID- 26992849 TI - Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice. AB - AIM: Effective therapy to treat acute pancreatitis (AP) or to prevent its recurrence/complication is still not available. Based on previous results that suggest that: i) hydrogen sulfide (H2S) levels were significantly increased in pancreatitis and gastritis and ii) Korean red ginseng (KRG) efficiently attenuated Helicobacter pylori-associated gastritis through the suppressive actions of H2S, we hypothesized that KRG can ameliorate experimental pancreatitis through suppression of H2S generation. METHODS: C57BL/6 mice were pre administered KRG and then subjected to cerulein injection or pancreatic duct ligation (PDL) to induce pancreatitis. Blood and pancreas tissues were collected and processed to measure serum levels of amylase, lipase and myeloperoxidase and the concentration of H2S and the levels of various inflammatory cytokine in pancreatic tissues of mice with induced AP. RESULTS: KRG significantly inhibited NaHS-induced COX-2 and TNF-alpha mRNA in pancreatic cells, but dl propargylglycine did not. KRG ameliorated cerulein-induced edematous pancreatitis accompanied with significant inactivation of NF-kappaB and JNK in pancreatic tissues of C57BL/6 mice (p < 0.001) and also significantly ameliorated PDL induced necrotizing pancreatitis (p<0.01); in both conditions, the significant suppression of H2S resulting from KRG pretreatment afforded rescuing outcomes. Along with suppressed levels of H2S consequent to depressed expressions of CBS and CSE mRNA, KRG administration efficiently decreased the serum level of amylase, lipase, and myeloperoxidase and the expression of inflammatory cytokines in animal models of mild or severe AP. CONCLUSIONS: These results provide evidence for the preventive and therapeutic roles of KRG against AP mediated by H2S suppression. PMID- 26992850 TI - Evaluation of the Spanish Urological Association quality care indicators in a kidney transplantation programme. AB - INTRODUCTION: Indicators show the presence of a phenomenon and its intensity. They assess the level of quality care and identify potential situations for improvement. Our objective is to assess the 2013 and 2014 quality care indicators of our department's kidney transplantation area. MATERIAL AND METHOD: For 2013 and 2014, we reviewed 88 and 106 kidney transplants and 47 and 66 extractions. We evaluated the quality care indicators developed by the Spanish Urological Association, analysing the results with the SPSS v 21.0 programme. RESULTS: The mean cold ischaemia time (CIT) was 14.96hours in 2013 and 18.07hours in 2014. The CIT was <=18h in 53% and 56% of cadaveric donor kidneys in 2013 and 2014, respectively. The rate of relevant early onset urinary fistulae was 1.14% and 2.83% for each year. The rate of early transplantectomy due to a vascular complication was 3.41% and 2.83% for 2013 and 2014, respectively. Overall patient survival at 1 year was 100% for both periods, and graft survival at 1 year was 95% and 94.34% for 2013 and 2014, respectively. The rate of living-donor transplantation was 14.77% and 17.92%, and 92.31% and 68.42% of the living-donor extractions were laparoscopic for 2013 and 2014, respectively. Resident medical interns were the first surgeon in 6.67% and 12.64% of the transplantations and in 55.88% and 19.14% of the cadaveric extractions during 2013 and 2014, respectively. CONCLUSIONS: During the evaluated period, all quality care standards in kidney transplantation were met, except for CIT in both years and resident medical intern participation in kidney implantation in 2013. This analysis promotes improvements in quality care, highlighting weak spots that need work. PMID- 26992852 TI - Erratum to: Health inequality in the Russian federation: an examination of the changes in concentration and achievement indices from 1994 to 2013. PMID- 26992851 TI - Characterization of multiple sequence alignment errors using complete-likelihood score and position-shift map. AB - BACKGROUND: Reconstruction of multiple sequence alignments (MSAs) is a crucial step in most homology-based sequence analyses, which constitute an integral part of computational biology. To improve the accuracy of this crucial step, it is essential to better characterize errors that state-of-the-art aligners typically make. For this purpose, we here introduce two tools: the complete-likelihood score and the position-shift map. RESULTS: The logarithm of the total probability of a MSA under a stochastic model of sequence evolution along a time axis via substitutions, insertions and deletions (called the "complete-likelihood score" here) can serve as an ideal score of the MSA. A position-shift map, which maps the difference in each residue's position between two MSAs onto one of them, can clearly visualize where and how MSA errors occurred and help disentangle composite errors. To characterize MSA errors using these tools, we constructed three sets of simulated MSAs of selectively neutral mammalian DNA sequences, with small, moderate and large divergences, under a stochastic evolutionary model with an empirically common power-law insertion/deletion length distribution. Then, we reconstructed MSAs using MAFFT and Prank as representative state-of-the-art single-optimum-search aligners. About 40-99% of the hundreds of thousands of gapped segments were involved in alignment errors. In a substantial fraction, from about 1/4 to over 3/4, of erroneously reconstructed segments, reconstructed MSAs by each aligner showed complete-likelihood scores not lower than those of the true MSAs. Out of the remaining errors, a majority by an iterative option of MAFFT showed discrepancies between the aligner-specific score and the complete likelihood score, and a majority by Prank seemed due to inadequate exploration of the MSA space. Analyses by position-shift maps indicated that true MSAs are in considerable neighborhoods of reconstructed MSAs in about 80-99% of the erroneous segments for small and moderate divergences, but in only a minority for large divergences. CONCLUSIONS: The results of this study suggest that measures to further improve the accuracy of reconstructed MSAs would substantially differ depending on the types of aligners. They also re-emphasize the importance of obtaining a probability distribution of fairly likely MSAs, instead of just searching for a single optimum MSA. PMID- 26992853 TI - A centrosome clustering protein, KIFC1, predicts aggressive disease course in serous ovarian adenocarcinomas. AB - BACKGROUND: Amplified centrosomes are widely recognized as a hallmark of cancer. Although supernumerary centrosomes would be expected to compromise cell viability by yielding multipolar spindles that results in death-inducing aneuploidy, cancer cells suppress multipolarity by clustering their extra centrosomes. Thus, cancer cells, with the aid of clustering mechanisms, maintain pseudobipolar spindle phenotypes that are associated with low-grade aneuploidy, an edge to their survival. KIFC1, a nonessential minus end-directed motor of the kinesin-14 family, is a centrosome clustering molecule, essential for viability of extra centrosome-bearing cancer cells. Given that ovarian cancers robustly display amplified centrosomes, we examined the overexpression of KIFC1 in human ovarian tumors. RESULTS: We found that in clinical epithelial ovarian cancer (EOC) samples, an expression level of KIFC1 was significantly higher when compared to normal tissues. KIFC1 expression also increased with tumor grade. Our In silico analyses showed that higher KIFC1 expression was associated with poor overall survival (OS) in serous ovarian adenocarcinoma (SOC) patients suggesting that an aggressive disease course in ovarian adenocarcinoma patients can be attributed to high KIFC1 levels. Also, gene expression levels of KIFC1 in high-grade serous ovarian carcinoma (HGSOC) highly correlated with expression of genes driving centrosome amplification (CA), as examined in publically-available databases. The pathway analysis results indicated that the genes overexpressed in KIFC1 high group were associated with processes like regulation of the cell cycle and cell proliferation. In addition, when we performed gene set enrichment analysis (GSEA) for identifying the gene ontologies associated to KIFC1 high group, we found that the first 100 genes enriched in KIFC1 high group were from centrosome components, mitotic cell cycle, and microtubule-based processes. Results from in vitro experiments on well-established in vitro models of HGSOC (OVSAHO, KURAMOCHI), OVCAR3 and SKOV3) revealed that they display robust centrosome amplification and expression levels of KIFC1 was directly associated (inversely correlated) to the status of multipolar mitosis. This association of KIFC1 and centrosome amplification with HGSOC might be able to explain the increased aggressiveness in this disease. CONCLUSION: These findings compellingly underscore that KIFC1 can be a biomarker that predicts an aggressive disease course in ovarian adenocarcinomas. PMID- 26992855 TI - [Trastuzumab emtansine in the systemic treatment of HER-2-positive breast cancer brain metastases]. PMID- 26992856 TI - Comment: Revisiting Lassen cerebral blood flow constancy with hysteresis and 3D. PMID- 26992854 TI - TNF-alpha promotes lymphangiogenesis and lymphatic metastasis of gallbladder cancer through the ERK1/2/AP-1/VEGF-D pathway. AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), a key player in cancer related inflammation, was recently demonstrated to be involved in the lymphatic metastasis of gallbladder cancer (GBC). Vascular endothelial growth factor D (VEGF-D) is a key lymphangiogenic factor that is associated with lymphangiogenesis and lymph node metastasis in GBC. However, whether VEGF-D is involved in TNF-alpha-induced lymphatic metastasis of GBC remains undetermined. METHODS: The expression of VEGF-D in patient specimens was detected by immunohistochemistry and the relationship between VEGF-D in the tissue and TNF alpha in the bile of the matching patients was analyzed. The VEGF-D mRNA and protein levels after treatment with exogenous TNF-alpha in NOZ, GBC-SD and SGC 996 cell lines were measured by real-time PCR and ELISA. The promoter activity and transcriptional regulation of VEGF-D were analyzed with the relative luciferase reporter assay, mutant constructs, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, RNA interference and Western blotting. Inhibitors of JNK, p38 MAPK and ERK1/2 were used to explore the upstream signaling effector of AP-1. We used lentiviral vector expressing a VEGF D shRNA construct to knockdown VEGF-D gene in NOZ and GBC-SD cells. The role of the TNF-alpha-VEGF-D axis in the tube formation of human dermal lymphatic endothelial cells (HDLECs) was determined using a three-dimensional coculture system. The role of the TNF-alpha - VEGF-D axis in lymphangiogenesis and lymph node metastasis was studied via animal experiment. RESULTS: TNF-alpha levels in the bile of GBC patients were positively correlated with VEGF-D expression in the clinical specimens. TNF-alpha can upregulate the protein expression and promoter activity of VEGF-D through the ERK1/2 - AP-1 pathway. Moreover, TNF-alpha can promote tube formation of HDLECs, lymphangiogenesis and lymph node metastasis of GBC by upregulation of VEGF-D in vitro and in vivo. CONCLUSION: Taken together, our data suggest that TNF-alpha can promote lymphangiogenesis and lymphatic metastasis of GBC through the ERK1/2/AP-1/VEGF-D pathway. PMID- 26992857 TI - Global cerebral edema from hypercapnic respiratory acidosis and response to hyperosmolar therapy. PMID- 26992859 TI - How to Bolster Emotional Intelligence Among Psychiatric Mental Health Nurses Clinicians. PMID- 26992858 TI - Frontotemporal networks and behavioral symptoms in primary progressive aphasia. AB - OBJECTIVE: To determine if behavioral symptoms in patients with primary progressive aphasia (PPA) were associated with degeneration of a ventral frontotemporal network. METHODS: We used diffusion tensor imaging tractography to quantify abnormalities of the uncinate fasciculus that connects the anterior temporal lobe and the ventrolateral frontal cortex. Two additional ventral tracts were studied: the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus. We also measured cortical thickness of anterior temporal and orbitofrontal regions interconnected by these tracts. Thirty-three patients with PPA and 26 healthy controls were recruited. RESULTS: In keeping with the PPA diagnosis, behavioral symptoms were distinctly less prominent than the language deficits. Although all 3 tracts had structural pathology as determined by tractography, significant correlations with scores on the Frontal Behavioral Inventory were found only for the uncinate fasciculus. Cortical atrophy of the orbitofrontal and anterior temporal lobe cortex was also correlated with these scores. CONCLUSIONS: Our findings indicate that damage to a frontotemporal network mediated by the uncinate fasciculus may underlie the emergence of behavioral symptoms in patients with PPA. PMID- 26992860 TI - Differences Between Irish and Australian Psychiatric Nurses' Family-Focused Practice in Adult Mental Health Services. AB - Psychiatric nurses' practice with parents who have mental illness, their children and families is an important issue internationally. This study provides a comparison of Irish and Australian psychiatric nurses' family-focused practices in adult mental health services. Three hundred and forty three nurses across Ireland and 155 from Australia completed the Family Focused Mental Health Practice Questionnaire. Cross-country comparisons revealed significant differences, in terms of family-focused skill, knowledge, confidence and practice. Australian psychiatric nurses engaged in higher family-focused practice compared to Irish nurses. The comparative differences between countries may be attributable to differences in training, workplace support and policy. PMID- 26992861 TI - "It didn't kill me. It just made me stronger and wiser": Silver Linings for Children and Adolescents of Parents with Chronic Pain. AB - Chronic non-cancer pain (CNCP) is a disease that affects adults in their child rearing years and is often incurable and of indefinite duration. Children and adolescents who live with parental CNCP can endure multiple adversities and experience subsequent emotional and somatic difficulties. Resilience is the ability to overcome adversity and even experience growth. This study is a secondary analysis of qualitative data, which sought to gain a deeper understanding of the ways in which children and adolescents rebound and grow from experiences living with parents who suffer with CNCP. Young adult children (N=30) of parents with CNCP were interviewed. Content analysis yielded five ways in which their experiences led to areas of positive growth: (a) expanded ways of understanding; (b) cultivated a strong character; (c) aided in the development of important skills; (d) instilled a commitment to live well, and; (e) nurtured spirituality. Clinicians who work with children and adolescents whose parents are disabled with CNCP can create environments that foster resilience and serve as a guide by helping these youth recognize potentials that have not yet been actualized and promoting positive change and growth over time. PMID- 26992862 TI - Efficacy of Group Motivational Interviewing in the Degree of Drug Craving in the Addicts Under the Methadone Maintenance Treatment (MMT) in South East of Iran. AB - BACKGROUND: Craving is one of the important factors having an effective role in the addiction relapse. As an important factor in the therapy failure, this clinical phenomenon has to be diagnosed and treated. OBJECTIVE: The present research aimed at determining the efficacy of group motivational interviewing in the degree of drug craving in the addicts under the Methadone Maintenance Treatment (MMT). METHOD: This is a quasi-experimental study carried out on 100 addicted men (aged 18-50 years), who were under the MMT in a drug abstinence clinic affiliated with University of Medical Sciences (Iran) in the second half of 2014. The research sample was selected by the availability criteria based on the inclusion and exclusion criteria, and upon matching, it was divided randomly into two groups of 50 (control and treatment). The treatment group first received 5 sessions of group motivational counseling; then it entered the therapy process. The control group received the usual treatment of the drug abstinence clinic. To assess the drug craving degree (in the pretest, 2, 6 and 12 months after the abstinence), the Visual Cue-induced Craving Task, scored 0 to 100, was used. The data were analyzed by the descriptive statistics through independent t-test, and repeated measures analysis of variance. RESULTS: The means of craving degrees in the control group, 2, 6 and 12 months after the abstinence (73.28 +/- 7.52, 65.83 +/- 6.69 and 61.25+/-5.17, respectively) were significantly (p=0.0001) higher than those in the treatment group (68.94 +/- 10.53, 40.48 +/- 11.78 and 32.51 +/- 9.00). Moreover, the mean of retention in the treatment was 9.24 +/- 2.45 months in the treatment group that was significantly (p=0.001) higher than the 4.88 +/- 3.65 months of retention in the control group. CONCLUSION: The research results support the fact that motivational interviewing decreases the degree of drug craving, and increases the probability of the addicts' retention in long-term therapeutic abstinence programs. Therefore, the use of such an approach as a pretreatment and a complementary therapy in changing health behaviors is recommended. PMID- 26992863 TI - Motivational Interviewing in a Patient With Schizophrenia to Achieve Treatment Collaboration: A Case Study. AB - Medication nonadherence decreases the success of clinical treatment and the efficient use of resources, thereby creating a barrier to effective health care. In this report, we describe the achievement of treatment collaboration through motivational interviews (MI) in a patient with treatment-resistant schizophrenia. In this case study, we conducted six MIs during which we asked open-ended and reflective questions, established empathy with the patient, and developed discrepancies, leading to ambivalent feelings being revealed. We used the importance, confidence and self-efficacy ruler. The MI method can be used to ensure continued treatment effectiveness, to increase patient awareness about the disease and benefits of treatment, and to increase patients' self-efficacy. PMID- 26992866 TI - Students' Perceptions of a Tobacco Education Intervention. AB - Persons living with a mental illness represent an especially vulnerable and disadvantaged subgroup of smokers. Compared to those in the general population, they smoke more, die younger, and suffer disproportionately from cardiovascular disease, diabetes, stroke, and cancer, all diseases and conditions directly associated with, and exacerbated by, smoking. Despite strong evidence that tobacco cessation counseling by a health professional can approximately double patients' odds of quitting, clinicians across disciplines are reluctant to offer these individuals effective means by which to quit smoking. This disinclination is due, at least in part, to inadequate tobacco cessation training during degree education. The purpose of this qualitative study was to assess undergraduate nursing students' perceptions of a tobacco education intervention. Findings support the integration of tobacco education into undergraduate nursing curricula. PMID- 26992865 TI - Suicidal Ideation on Higher Education Students: Influence of Some Psychosocial Variables. AB - INTRODUCTION: While attending to higher education, multiple changes occur in the lives of young students. These changes make higher education students particularly more exposed and vulnerable to mental health problems, and therefore more likely to present suicidal behaviors. OBJECTIVES: The aim of this study was to assess suicidal ideation in higher education students, and its relationship with some psychosocial variables. METHODS: Exploratory, quantitative and descriptive study, applied on a sample of 1074 students of a higher education institution in Portugal. RESULTS: Some significant associations with suicidal ideation were found with self-concept factors (self-acceptance, self effectiveness and impulsivity); stress, anxiety and clinical depression; linkage anxiety and social support activities dimensions; intimacy and total social support. CONCLUSION: In our sample we found 84 students with potential suicidal risk, and through the result analysis, the biopsychosocial profile of the student at risk for suicidal ideation exhibits the following traits: female, age 18/19, low self-concept, insecure linkage patterns and little involvement in social activities and intimacy relationships. All facts considered, higher education institutions should provide programs that promote mental health and suicide prevention in academic environments. The results of this study also have implications for policy makers, clinical practice, suicide prevention and higher education institutions. PMID- 26992864 TI - Gardening/Yard Work and Depressive Symptoms in African Americans. AB - BACKGROUND: The purpose of this study was to examine the frequency of gardening/yard work in relation to depressive symptoms in African-Americans while controlling for biological and social factors. METHODS: A secondary analysis was performed on the National Survey of American Life (n=2,903) using logistic regression for complex samples. Gardening/Yard work was measured by self-reported frequency. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression scale. RESULTS: Biological and social factors, not gardening/yard work, were associated with depressive symptoms. CONCLUSIONS: Biological and social factors may need to be addressed before the association between gardening/yard work and depressive symptoms can be determined. PMID- 26992867 TI - Exploring the Needs for Support of Pediatric Nurses Caring for Children with a Mental Health Disorder Hospitalized in Non-Psychiatric Units. AB - This qualitative study explored the experience and the needs for support of pediatric nurses caring for children with a mental health disorder hospitalized in non-psychiatric units in a health organization in Canada. Semi-structured interviews were conducted with 17 nurses. Content analysis revealed two main themes: (a) nurses are challenged by the lack of knowledge, the gap between access to mental health resources and the basic role of only ensuring safety. Amidst these barriers, nurses revealed their feelings of helplessness, frustration and injustice. (b) All participants voiced their willingness to break this powerlessness loop. They identified several strategies to support them: more training in mental health, better collaboration with the mental health team, etc. Further research is needed to evaluate the efficiency of these strategies to improve the delivery of care for children with a mental health disorder hospitalized in non-psychiatric units. PMID- 26992868 TI - Sense of Belonging and Hope in the Lives of Persons with Schizophrenia. AB - This qualitative study used semi-structured interviews to explore the meaning of sense of belonging and hope in the lived experiences of 20 persons with chronic schizophrenia-spectrum disorders receiving acute inpatient treatment. Experience of treatment was also explored. Sense of belonging and hope were both identified as valuable or even vital, yet the experiences of not belonging and/or feeling hopeless was more prevalent. Participants frequently felt like an outsider and experienced loneliness and isolation, suggesting a need for further exploration of the impact of sense of belonging and hope on recovery and even treatment adherence in persons with schizophrenia. PMID- 26992870 TI - Probable Post-Traumatic Stress Disorder and Its Predictors in Disaster-Bereaved Survivors: A Longitudinal Study After the Sichuan Earthquake. AB - This study examined the trajectory of probable PTSD prevalence and severity, and analyzed the predictors for PTSD severity in bereaved survivors at 6 months and 18 months after the 2008 Sichuan earthquake. This was a longitudinal study with 226 bereaved survivors sampled at 6 months and 18 months post-earthquake. The instrument used in the study was the revised version of the Impact of Event Scale. The results showed that the prevalence of probable PTSD in bereaved survivors decreased significantly from 38.9% at 6 months to 16.8% at 18 months post-earthquake. Loss of a child, being directly exposed to the death of family members and property loss during the earthquake, and mental health services utilization after the earthquake were significant predictors for PTSD severity at both assessments. These findings can contribute to post-disaster psychological rescue work. The bereaved survivors at high risk for more severe PTSD should be particularly targeted. PMID- 26992869 TI - Post-Traumatic Stress Disorder Among Health Care Providers Following the Israeli Attacks Against Gaza Strip in 2014: A Call for Immediate Policy Actions. AB - PURPOSE: This study aimed to assess the level of posttraumatic stress disorder and to examine the relationship between exposure to war stress and posttraumatic symptoms among health care providers following Israeli offensives against Gaza Strip in 2014. METHODOLOGY: A cross-sectional design was used for this study. We targeted all nurses and doctors working in three governmental hospitals in the Gaza Strip and worked with victims of the last war, more specifically, those who were working in emergency departments, intensive care units, operating rooms, surgical departments, and burn units. A demographic sheet and Impact Event Scale Revised were used in this study. The Impact Event Scale-Revised has three sub scales; intrusion, avoidance, and hyper-arousal. RESULTS: The results showed that 291 (89.8%) of 324 participants had scores more than 35 (threshold cut-off point) on the Impact Event Scale-Revised. Scores ranged from zero to 80 with a mean of 52.13. Females had higher levels of stress (55.79) than males (51.63) and nurses (54.85) had more stress than physicians (47.38). The most frequent symptoms of trauma subscales was "avoidance" (mean=20.04), followed by "intrusion" (mean=17.83), and then "hyper-arousal" (mean=14.27). Levels of trauma symptoms were not affected by place of living, hospital of work, while level of education had impacted level of trauma. CONCLUSION: The findings showed that health care providers suffered from severe posttraumatic symptoms after exposure to prolonged war stress. This level of trauma among health care providers warrants intervention programs to reduce stress and trauma among Gaza health care providers after the war. PMID- 26992871 TI - Suicide Ideation and Life Events in a Sample of Rural Adolescents. AB - Adolescents experience both developmental and situational periods of transition along with myriad stressful life events when they enter and exit high school. These life events may be associated with thinking of, planning, and attempting suicide. Yet despite the development of prevention programs to treat at-risk individuals, suicide rates among adolescents have remained relatively high. Recent research suggests that suicidal ideation is associated with stressful life events and the use of maladaptive coping mechanisms, but studies have been limited to cross-sectional designs and clinical samples. We conducted a longitudinal study of 1345 rural adolescents (50.7% Hispanic) attending public schools in central Texas. The purpose of this analysis was to determine changes in suicide ideation rates over time and to test hypotheses about the life events and coping mechanisms associated with suicide ideation. Gender and race/ethnic differences in suicide were also explored. Rates of reported suicide ideation declined significantly from the first to the last year of high school (p=.015). Statistically significant relationships were found between suicide ideation, several types of life events, and maladaptive coping strategies. Gender and racial/ethnic differences were also found. Taken together, these findings suggest new approaches to developing and testing interventions that can assist specific populations of adolescents to learn how to cope with their life events in productive and health-promoting ways. PMID- 26992872 TI - The Experience of Cancer Stigma in Taiwan: A Qualitative Study of Female Cancer Patients. AB - BACKGROUND: Cancer is the leading cause of death in Taiwan. Because the causes of cancer are often difficult to identify, a diagnosis of cancer is occasionally attributed to karma and the concept of stigma. These feelings lead to a life predicament, and stigma influences these perceptions. OBJECTIVE: This study intended to understand how stigma is formed in the disease-related experiences of women with cancer. METHODS: Ten participants were interviewed at the time of a confirmed diagnosis of advanced cancer and completed cancer treatment with regular follow-up after treatment, and all subjects underwent 2-3 interviews. The number of interviews conducted was determined by data saturation. A content analysis method was used. RESULTS: The stigma of cancer includes the concepts of "cancer equals death", including the feeling of death approaching and an awareness of disease severity. "Cancer equals menace to social life" suggests that social life is affected and includes other individuals' uncomfortable attitudes toward cancer (shame, sympathy, pity, suffering, and over-cautiousness) and external physical changes. "Cancer equals cancer-ridden life" includes being sensitive to the topics of death and calculating the number of remaining survival days. CONCLUSIONS: The process from early diagnosis to the decision to receive treatment is complicated for patients with cancer. After the diagnosis is confirmed, the stigma of diagnosis significantly affects patients. Regarding social stereotypes, educating the public to resolve individuals' negative responses to cancer and further convey social and public information to women in society is necessary. PMID- 26992873 TI - Implementing the Use of a Brief Cognitive Assessment on Individuals Diagnosed With Schizophrenia in an Acute Psychiatric Facility. AB - Cognitive impairments are prevalent in schizophrenia. The use of a brief cognitive assessment allows for early detection and improves functional outcomes. The purpose of this quality improvement study was to implement the Montreal Cognitive Assessment (MoCA) into the nursing admission assessment for patients who are diagnosed with schizophrenia or related disorders. Nurses administered the MoCA in 67.3% of eligible patients. The high acuity and uncooperative states were the major barriers to screening. The majority of nurses reported confidence in their ability to perform the screening and believed that the results triggered clinical actions to address psychosocial or cognitive deficits. PMID- 26992874 TI - Dealing With Existential Suffering of Patients With Severe Persistent Mental Illness: Experiences of Psychiatric Nurses in Flanders (Belgium). AB - Residential psychiatric patients with severe persistent mental illness are often confronted with unbearable existential suffering. This qualitative study aims to describe how psychiatric nurses in Flanders (Belgium) deal with these patients. In view of the data we describe the nursing support for the existential suffering of these patients in terms of a process-related development. In this process of care four phases can be distinguished: meeting and knowing the patient, acknowledging the patient as an individual and as a sufferer, building a personal caring relationship based on a bond of trust and on respect for the patient as person, and a concluding phase. The personal caring relationship between nurse and patient is the fundamental element in the care practices. Next we describe the contextual framework inasmuch it can influence the caring process in a restricting or stimulating way. PMID- 26992876 TI - Aging With Schizophrenia: A Lifelong Experience of Multidimensional Losses and Suffering. AB - The aim of this study was to explore the subjective experience of suffering in aging individuals with schizophrenia. Qualitative interviews were conducted with 18 participants aged 60-69. Phenomenological content analysis was performed. Nine dimensions of suffering emerged: social rejection; familial rejection; the symptoms of schizophrenia; hospitalisation; the side effects of medication; loss of employment potential; loss of independent accommodation; loss of social life, and loss of hope to be a partner and a parent. The suffering of aging people with schizophrenia is cumulative and ongoing and thus evokes issues such as existential loneliness and feelings of homelessness. PMID- 26992875 TI - A Preliminary Analysis of Individuals With Serious Mental Illness and Comorbid Diabetes. AB - OBJECTIVE: To understand factors related to managing illness in older individuals with serious mental illness (SMI). METHODS: Baseline data from 200 individuals with SMI and diabetes enrolled in a study were used to compare characteristics between older (age >55) vs. younger (age <=55) individuals. RESULTS: Older individuals had better diabetes control compared to younger individuals, those with major depressive disorder had diabetes for a longer duration, worse diabetic control, and more emergency department encounters. CONCLUSIONS: Helping younger individuals with SMI learn to manage their mental and physical health early-on might minimize the negative and cumulative effect of diabetes. PMID- 26992877 TI - Burden and Cognitive Appraisal of Stroke Survivors' Informal Caregivers: An Assessment of Depression Model With Mediating and Moderating Effects. AB - This study proposes and evaluates a model of depression that concerns the role of burden and cognitive appraisal as mediators or moderators of outcomes among stroke survivor caregivers. A total of 105 informal caregivers of stroke survivor completed the self-report measures of Caregiver Burden Inventory, Center for Epidemiologic Studies Depression Scale, and Cognitive Impact of Appraisal Scale. The Glasgow Coma Scale and Barthel Index were used by the researcher to examine the physical functional status of the survivor. Partial least squares (PLS) path modeling was used to estimate the parameters of a depression model that included mediating or moderating effects. The model shows that burden and impact of cognitive appraisal have a significant direct and indirect impact on depression, while survivor physical functional status does not have a direct impact. The model also demonstrates that burden and impact of cognitive appraisal separately play a mediating role between survivor physical functional status and caregiver depression. In addition, cognitive appraisal has a moderating influence on the relationship between burden and depression. Overall, survivor physical functional status, burden, and cognitive appraisal were the predictors of caregiver depression, explaining 47.1% of the variance. This study has shown that burden and cognitive appraisal are mediators that more fully explain the relationship between patient severity and caregiver depression. PMID- 26992879 TI - Effectiveness of Adherence Therapy for People With Schizophrenia in Turkey: A Controlled Study. AB - OBJECTIVE: This study used a quasi-experimental design with a pretest-posttest control group and follow-up to determine the efficacy of adherence therapy in patients with schizophrenia in Turkey. METHODS: The sample of this study consisted of patients with schizophrenia (n=30). The Questionnaire Form, Medication Adherence Rating Scale, Internalized Stigma of Mental Illness Scale, and Beck Cognitive Insight Scale were used. The patients were assigned to experimental (n=15) and control (n=15) groups using the randomization method. The experimental group received adherence therapy in eight sessions. RESULTS: When the scores of the patients in the experimental and control groups were compared at the pretest, posttest, and 3- and 6-months follow ups, a significant difference was only found in the Medication Adherence Rating Scale posttest scores. CONCLUSION: Adherence therapy is effective in improving adherence to treatment but is not effective with regard to insight and internalized stigma in patients with schizophrenia. PMID- 26992878 TI - Rural Women Veterans' Use and Perception of Mental Health Services. AB - While the total number of veterans in the U.S. is decreasing overall, the number of women veterans is significantly increasing. There are numerous barriers which keep women veterans from accessing mental health care. One barrier which can impact receiving care is living in a rural area. Veterans in rural areas have access to fewer mental health services than do urban residing veterans, and women veterans in general have less access to mental health care than do their male colleagues. Little is known about rural women veterans and their mental health service needs. Women, who have served in the military, have unique problems related to their service compared to their male colleagues including higher rates of post-traumatic stress disorder (PTSD) and military sexual trauma (MST). This qualitative study investigated use of and barriers to receiving mental health care for rural women veterans. In-depth interviews were conducted with ten women veterans who have reported experiencing problems with either MST, PTSD, or combat trauma. All ten women had utilized mental health services during active-duty military service, and post service, in Veterans Administration (VA) community based-outpatient clinics. Several recurring themes in the women's experience were identified. For all of the women interviewed, a sentinel precipitating event led to seeking mental health services. These precipitating events included episodes of chronic sexual harassment and ridicule, traumatic sexual assaults, and difficult combat experiences. Efforts to report mistreatment were unsuccessful or met with punishment. All the women interviewed reported that they would not have sought services without the help of a supportive peer who encouraged seeking care. Barriers to seeking care included feeling like they were not really a combat veteran (in spite of serving in a combat unit in Iraq); feeling stigmatized by providers and other military personnel, being treated as crazy; and a lack of interest from those providing care in hearing their stories. This study may generate positive social change by helping providers approach women veterans in a way that is sympathetic to their experiences. PMID- 26992880 TI - Residential Instability Among Low-Income Families: A Concept Analysis. AB - Residential instability is relatively common among low-income families and is associated with a host of negative outcomes, especially for children and adolescents. Psychiatric nurses, especially those in the advanced practice role, observe the consequences of residential instability within the clinical setting. Yet, to-date, the concept is somewhat vague and its essential meaning and definition remain unclear. The aim of this paper is to develop a definition of residential instability using Wilson's method of concept analysis. An overview of historical perspectives is included. The paper concludes with recommendations for future research and application within clinical practice. PMID- 26992881 TI - Medical-Surgical Nurses' Perceptions of Psychiatric Patients: A Review of the Literature With Clinical and Practice Applications. AB - The literature consistently shows that medical-surgical nurses frequently lack the knowledge, skills, and attitudes necessary to render holistic nursing care to patients with severe mental illness (SMI). The negative perceptions often portrayed by medical-surgical nurses towards SMI patients with comorbid medical surgical disorders must be addressed in order to ameliorate treatment gaps. Current concepts, issues, and challenges associated with the perceptions of nurses who care for patients with (SMI) in medical-surgical settings can prove overwhelming to both nurses and patients, and can result in concerning practice gaps. In accordance with a contemporary model of patient-centered care, it is imperative that medical-surgical nurses acquire the knowledge, skills, and attitudes necessary to work with this high-risk population. Cultivating an environment that promotes apposite attitudes along with effective training programs for medical-surgical nurses, may shift negative perceptions and ultimately meet best practice standards and improve outcomes for patients with SMI. PMID- 26992882 TI - A Review of Instruments on Cognitive Appraisal of Stress. AB - PURPOSE: The purpose of this paper is to present a review of theoretically based measures of cognitive appraisal, and discuss psychometric strengths and limitations. BACKGROUND: Understanding how an individual appraises stressful events becomes important when faced with alterations in mental health. Cognitive appraisals influence how an individual copes with stressful events and life crises that leads to changes in mental health. Measures on how an individual appraises a stressful event lack conceptual soundness and are limited by weak psychometric properties. DATA SOURCES: Health and Psychosocial Instruments (HAPI) electronic database was searched using combinations of the key words cognitive appraisal, primary appraisal, secondary appraisal, appraisal of illness, appraisal of health, and stress appraisal. The quality of these instrument sources was assessed by published psychometric data in the primary source. RESULTS: Five instruments were found that measure cognitive appraisal as theoretically described: the Meaning of Illness Questionnaire, the Stress Appraisal Measure, the Appraisal of Illness Scale, the Cognitive Appraisal of Health Scale, and the Primary Appraisal/Secondary Appraisal scale. A description of each tool, including purpose, scoring, and psychometric support, is provided. CONCLUSION: There are a limited number of instruments that measure cognitive appraisal as theoretically described. Theoretically sound instruments with established psychometric support are needed to make accurate inferences about the role of cognitive appraisal in the mental and physical health of individuals experiencing stress. PMID- 26992883 TI - Mental Health Needs of People Who Identify as Transgender: A Review of the Literature. AB - Transgender people face many challenges in society including accessing and using healthcare systems. However, little is known about the specific mental health service needs and concerns of transgender people in this regard. The aim of the study was to establish the mental health service needs of transgender people through a review of relevant studies that address the experiences and views of this group. A comprehensive search of CINHAL, Cochrane, Google Scholar, PubMed, PsychInfo, PsychLit, Sociological Abstracts, Scopus, and Web of Science databases from inception to January 2014 was conducted. Studies were identified that met specific criteria that included: using qualitative methods, involving transgender people, and addressing issues related to mental health services. The search yielded 217 papers in total. Following the application of rigorous inclusion and exclusion criteria 33 papers were included for retrieval. Finally, 10 papers were considered suitable for the review. The data were analyzed and key themes identified. The review highlighted distinct challenges that exist in terms of mental health service provision. These included accessing appropriate services and treatments, responsiveness of practitioner's, the provision of family supports and potential mental health service developments. The review findings are discussed and key recommendations are made in terms of mental health nursing practice developments, education and research. PMID- 26992884 TI - Mental Health Nursing of Adults With Intellectual Disabilities and Mental Illness: A Review of Empirical Studies 1994-2013. AB - Mental health nursing for adults with intellectual disabilities and mental illness is underresearched. The aim of this review is to summarize empirical mental health nursing studies including adults with intellectual disabilities and additional mental illness. Out of 137 hits, 16 articles were reviewed in full text. Thirteen of the articles presented modified nursing interventions. Three articles discussed training and education. The main finding is that mental health nursing interventions in patients with intellectual disabilities and additional mental illness are in line with mental health nursing for the general population. There are still not many publications on empirical studies concerning mental health nursing for adults with intellectual disabilities. Clinical implications are primarily related to the need for facilitated nurse-patient communication adjusted to the patients' cognitive levels. Insights drawn from this review illuminate the importance of mental health nursing interventions adjusting to the particular patients' symptoms, instead of targeting behavior change. The findings underpin factors found to have a positive impact on patients with mental illness in the general population as relevant topics for future research. PMID- 26992885 TI - The Effects of Mindfulness-Based Stress Reduction for Family Caregivers: Systematic Review. AB - Caring for patients with various conditions is demanding and stressful and can have a negative impact on both physical and psychological health. This paper reports a systematic review and critical appraisal of the evidence on the effectiveness of mindfulness-based stress reduction for the family caregivers of patients with various conditions. There were improvements in the self-rated psychological symptoms, such as stress, depression, anxiety and mindfulness. To conclude, mindfulness-based stress reduction, as a safe and transportable approach, has potential to improve the psychological symptoms in the caregivers of patients with various conditions. PMID- 26992887 TI - An Overview of the Pathogenesis of Immune-mediated Skin Injury. AB - The skin has a relatively limited range of responses to injury regardless of the specific mechanism underlying the insult. When the skin's barrier function is disrupted, it mounts an inflammatory and proliferative response in an effort to restore this essential function. The epidermal keratinocyte is central to the initiation of the skin's response, triggering an immunologic cascade that leads to the stereotypic morphologic responses that we encounter as pathologists. Drug induced immune-mediated cutaneous injuries or "drug eruptions" are relatively common, sometimes with overlapping mechanisms, and it is often possible to classify these based on the classical hypersensitivity-type reactions. A specific type of immune-mediated skin injury is psoriasis. The pathogenesis of psoriasis is multifactorial but involves the interaction of environmental factors with a genetic predisposition. The initial stimulus triggering the development of psoriatic lesions involves activation of epidermal keratinocytes, with subsequent amplification driven by cross talk between the adaptive and innate immune systems. Several cytokines produced by Th17 T helper cells have recently been shown to be important in the pathogenesis of psoriasis, namely, interleukin-23 (IL-23) and IL-17, due to demonstrated clinical efficacy of cytokine blockade; and IL-22, based on its effects in both in vitro and in vivo models. PMID- 26992886 TI - Hepatic Responses of Juvenile Fundulus heteroclitus from Pollution-adapted and Nonadapted Populations Exposed to Elizabeth River Sediment Extract. AB - Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries region of the Elizabeth River, Virginia, have passed polycyclic aromatic hydrocarbon (PAH) resistance to their offspring as evidenced by early life stage testing of developmental toxicity after exposure to specific PAHs. Our study focused on environmentally relevant PAH mixtures in the form of Elizabeth River sediment extract (ERSE). Juvenile (5 month) F1 progeny of pollution-adapted Atlantic Wood (AW) parents and of reference site (King's Creek [KC]) parents were exposed as embryos to ERSE. Liver alterations, including nonneoplastic lesions and microvesicular vacuolation, were observed in both populations. ERSE-exposed KC fish developed significantly more alterations than unexposed KC fish. Interestingly, unexposed AW killifish developed significantly more alterations than unexposed KC individuals, suggesting that AW juveniles are not fully protected from liver disease; rapid growth of juvenile fish may also be an accelerating factor for tumorigenesis. Because recent reports show hepatic tumor formation in adult AW fish, the differing responses from the 2 populations provided a way to determine whether embryo toxicity protection extends to juveniles. Future investigations will analyze older life stages of killifish to determine differences in responses related to chronic disease. PMID- 26992889 TI - Current understanding and neurobiology of epileptic encephalopathies. AB - Epileptic encephalopathies are a group of diseases in which epileptic activity itself contributes to severe cognitive and behavioral impairments above and beyond what might be expected from the underlying pathology alone. These impairments can worsen over time. This concept has been continually redefined since its introduction. A few syndromes are considered epileptic encephalopathies: early myoclonic encephalopathy and Ohtahara syndrome in the neonatal period, epilepsy of infancy with migrating focal seizures, West syndrome or infantile spasms, Dravet syndrome during infancy, Lennox-Gastaut syndrome, epileptic encephalopathy with continuous spikes-and-waves during sleep, and Landau-Kleffner syndrome during childhood. The inappropriate use of this term to refer to all severe epilepsy syndromes with intractable seizures and severe cognitive dysfunction has led to confusion regarding the concept of epileptic encephalopathy. Here, we review our current understanding of those epilepsy syndromes considered to be epileptic encephalopathies. Genetic studies have provided a better knowledge of neonatal and infantile epilepsy syndromes, while neuroimaging studies have shed light on the underlying causes of childhood-onset epileptic encephalopathies such as Lennox-Gastaut syndrome. Apart from infantile spasm models, we lack animal models to explain the neurobiological mechanisms at work in these conditions. Experimental studies suggest that neuroinflammation may be a common neurobiological pathway that contributes to seizure refractoriness and cognitive involvement in the developing brain. PMID- 26992888 TI - Rapamycin prevents, but does not reverse, aberrant migration in Pten knockout neurons. AB - Phosphatase and tensin homolog (PTEN) is a major negative regulator of the Akt/mammalian target of rapamycin (MTOR) pathway. Mutations in PTEN have been found in a subset of individuals with autism and macrocephaly. Further, focal cortical dysplasia (FCD) has been observed in patients with PTEN mutations prompting us to examine the role of Pten in neuronal migration. The dentate gyrus of Pten(Flox/Flox) mice was injected with Cre- and non-Cre-expressing retroviral particles, which integrate into the dividing genome to birthdate cells. Control and Pten knockout (KO) cell position in the granule cell layer was quantified over time to reveal that Pten KO neurons exhibit an aberrant migratory phenotype beginning at 7.5days-post retroviral injection (DPI). We then assessed whether rapamycin, a mTor inhibitor, could prevent or reverse aberrant migration of granule cells. The preventative group received daily intraperitoneal (IP) injections of rapamycin from 3 to 14 DPI, before discrepancies in cell position have been established, while the reversal group received rapamycin afterward, from 14 to 24 DPI. We found that rapamycin prevented and reversed somal hypertrophy. However, rapamycin prevented, but did not reverse aberrant migration in Pten KO cells. We also find that altered migration occurs through mTorC1 and not mTorC2 activity. Together, these findings suggest a temporal window by which rapamycin can treat aberrant migration, and may have implications for the use of rapamycin to treat PTEN-mutation associated disorders. SIGNIFICANCE STATEMENT: Mutations in phosphatase and tensin homolog (PTEN) have been linked to a subset of individuals with autism and macrocephaly, as well as Cowden Syndrome and focal cortical dysplasia. Pten loss leads to neuronal hypertrophy, but the role of Pten in neuronal migration is unclear. Here we have shown that loss of Pten leads to aberrant migration, which can be prevented but not reversed by treatment with rapamycin, a mTor inhibitor. These results are important to consider as clinical trials are developed to examine rapamycin as a therapeutic for autism with PTEN mutations. Our findings show that some abnormalities cannot be reversed, and suggest the potential need for genetic screening and preventative treatment. PMID- 26992890 TI - Psychometric assessment and behavioral experiments using a free virtual reality platform and computational science. AB - BACKGROUND: Virtual Reality has been extensively used in a wide range of psychological experiments. In this study, we aimed to introduce NeuroVirtual 3D, a platform that clinicians could use free of charge. IMPLEMENTATION: The platform we developed relies on NeuroVR software, but we extended it to apply to experiments. The software is available free of charge to researchers and clinical practitioners who can also use a large number of virtual environments and objects already developed. RESULTS: The platform has been developed to connect to virtually every device ever produced by the means of Virtual-Reality Peripheral Network (VRPN) protocols; however, a number of these have already been included and tested in the platform. Among the available devices, the Microsoft Kinect low cost sensor has already been configured for navigation through the virtual environments and to trigger specific action (sounds, videos, images, and the like) when a specific gesture is recognized, e.g., a step forward or an arm up. A task for neglect and a task for spatial abilities assessment were already implemented within the platform. Moreover, NeuroVirtual 3D integrated a TCP-IP based module (bridge) to collect the data from virtually any existent biosensor (Thought-Technology, Zephyr and StarStim devices have already been included in the platform). It is able to record any psychophysiological signal during any experiment using also the computed indices in real time. CONCLUSIONS: NeuroVirtual 3D is able to record external and internal (e.g., coordinates, keys press, timestamp) data with a millisecond precision, representing de facto the most advanced technology for experimental psychology using virtual environments available without the needs to program code. PMID- 26992891 TI - Association of HBV DNA replication with antiviral treatment outcomes in the patients with early-stage HBV-related hepatocellular carcinoma undergoing curative resection. AB - BACKGROUND: It remains unclear what the antiviral therapy affects disease-free survival (DFS) and overall survival (OS) of patients with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) at different tumor stages and baseline HBV DNA levels. In this study, we analyzed the association of antiviral treatment with DFS and OS based on the stratification of baseline HBV DNA load in early stage (stages I and II) HCC patients. METHODS: We included 445 patients with early-stage HBV-related HCC who underwent curative resection, and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification. The Kaplan-Meier and Cox regression analyses were performed to determine the association of clinical characteristics with survival. RESULTS: The median follow-up period was 74 months. For all patients, cumulative OS rates in the antiviral group were significantly higher than those in the non-antiviral group (log-rank test, P = 0.023), whereas no significant differences in DFS rates were observed. High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients. In patients with baseline HBV DNA levels >=2000 IU/mL, antiviral treatment was significantly associated with prolonged DFS and OS (log-rank test, P = 0.041 and 0.001, respectively). In patients with HBV DNA levels <2000 IU/mL or undetectable, antiviral treatment did not show a significant benefit in prolonging DFS and OS. CONCLUSIONS: High baseline HBV DNA levels are associated with poor prognosis in the patients with early-stage HCC, and the antiviral treatment could generate survival benefits for the patients. Therefore, antiviral treatment should be given for these patients. However, the effect of antiviral treatment on the patients with low viral load remains unclear, and further investigation is warranted. PMID- 26992892 TI - Effects of selenium on ischaemia-reperfusion injury in a rat testis model. AB - Selenium is shown to have beneficial effects on ischaemia-reperfusion (IR) injury. Our aim was to assess the effects of selenium on IR-induced testicular damage in terms of biochemical and histopathological evaluation. A total of 32 rats were randomised into four groups: control, IR, IR + selenium (IR + S) and S. Detorsion was applied after 3 h of torsion. Testicular tissue superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC) and DNA fragmentation levels were determined. Testicular tissue samples were examined by histopathological examination and terminal deoxynucleotidyl transferase dUTP nick end-labelling staining. The control, IR and IR + S groups had higher SOD values compared with the S group; SOD levels of the control and IR + S groups were higher than those of the IR group (P < 0.05). Further, MDA levels of the IR group were higher than those in the other three groups (P < 0.05). The IR group revealed lower TAC levels than the three groups (P < 0.05 for all). GSH levels of the IR group were significantly lower than those in the other three groups (P < 0.05 for all). In contrast, GSH levels of the IR + S group increased compared with those of the S group. The IR group had more DNA fragmentation than the control and S groups (P < 0.05). It is concluded that selenium possibly reduces oxidative stress and apoptosis caused by testicular IR injury in rats. The testicular protective effect of selenium appears to be mediated through its anti-apoptotic and antioxidative effects. However, selenium does not affect DNA fragmentation. PMID- 26992893 TI - Intestinal Infections Among Febrile Hospitalized Patients in the Republic of Armenia: A Retrospective Chart Review. AB - In the past, several enteric outbreaks in 1996, 1998, 1999, and 2003 caused by Salmonella typhi, a Gram-negative bacterium, have occurred in Armenia. This study describes the demographic, epidemiological, and clinical characteristics of febrile hospitalized patients with intestinal infections in Armenia. Using a chart review study design, medical data from adult patients who were hospitalized at the Nork hospital during 2010-2012 were reviewed. A total of 600 medical charts were reviewed. Of these, 51 % were diagnosed with intestinal infections. Among these patients, 59 % had an intestinal infection of known etiology, with three main pathogens identified: Salmonella sp. (32 %), Shigella sp. (32 %), and Staphylococcus aureus (18 %). After controlling for the calendar year, age in years, and gender, patients detected with Salmonella sp. were more likely to reported the presence of a family member with similar signs or symptoms [odds ratio (OR) 9.0; 95 % CI 2.4-33.7] and the lack of a water tap at home (OR 3.9; 95 % CI 1.7-9.5). Evidence indicates that Salmonella sp., Shigella sp., and S. aureus as the most common etiologies reported among febrile hospitalized patients. A high percentage of patients had intestinal infections of unknown etiology; thus, improvement in laboratory capacity (enabling more advanced tests, such as polymerase chain reaction) would increase the identification of the enteropathogens causing disease in Armenia. PMID- 26992894 TI - A Matched Cohort Analysis of Sleeve Gastrectomy With and Without 300 cm Loop Duodenal Switch With 18-Month Follow-Up. AB - BACKGROUND: In bariatric surgery, a significant question remains unanswered-What proportion of weight loss comes from each component and does this differ with time? Single anastomosis duodenal switch (LDS) combines a vertical sleeve gastrectomy (VSG) with a loop attachment of the duodenal stump. There are two major variables the sleeve, and the intestine that processes ingested food. A comparison of patients that had a VSG with those that have had a LDS approximates the contribution of each component. METHODS: A retrospective matched cohort analysis of VSG and LDS patients was obtained by matching every LDS patient to a VSG patient of the same sex and BMI. Excess weight lost percentage (%EWL) and the total weight loss percentage (%TWL) was analyzed. The data was compared through descriptive statistics and non-linear regression analysis. RESULTS: Over 18 months, patients who received the LDS lost more %TWL and %EWL and the difference was statistically significant (p < 0.05). Additionally, with time, the difference became more profound. Weight loss stabilized at approximately 9-12 months and 15 to 18 for VSG and LDS patients', respectively. At 6 months post op, there was approximately 13 % difference in weight loss. This increased to 29 % difference at 18 months. CONCLUSION: LDS patients lose more weight than VSG. Preserving 3 m of intestinal length adds 30 % greater weight loss at 18 months. Early weight loss is similar between the two operations, while the intestinal component becomes more important with weight loss differentials increasing as time since surgery lengthens. PMID- 26992895 TI - Gastric Perforation following Intragastric Balloon Insertion: Combined Endoscopic and Laparoscopic Approach for Management: Case Series and Review of Literature. AB - BACKGROUND: Obesity is a serious disease, with substantial morbidity and mortality. The endoscopic placement of an intragastric balloon (IGB) in association with a low-calorie diet is an option for the treatment of obesity. IGB complications include dislocation of the balloon causing intestinal obstruction, upper gastro-intestinal bleeding and perforation, especially during balloon insertion or removal. Our work aims at decreasing the morbidity of open laparotomy in the management of such gastric perforations. METHODS: We report three cases of gastric perforation following IGB insertion that needed surgical intervention. Decision was made to treat them with a minimally invasive combined endoscopic and laparoscopic approach to decrease postoperative morbidity. RESULTS: All patients were successfully treated by a minimally invasive approach with less morbidity than the conventional open laparotomy. CONCLUSION: Gastric perforation should be suspected in any patient with IGB who presents with an acute abdomen. This can be managed with a minimal invasive approach. PMID- 26992896 TI - Robot-Assisted Versus Laparoscopic Sleeve Gastrectomy: Learning Curve, Perioperative, and Short-Term Outcomes. AB - BACKGROUND: Currently, sleeve gastrectomy is most commonly performed laparoscopically. However, robot-assisted approach for sleeve gastrectomy is increasing in number among bariatric surgeons. The aim of our study is to compare perioperative outcomes of robot-assisted (RA-LSG) and laparoscopic sleeve gastrectomy (LSG). METHODS: Between June 2008 and December 2014, 647 patients underwent LSG and RA-LSG at our institution. A retrospective review was performed for 379 LSG and 268 R-LSG patients, noting the outcomes and complications of the procedure. RESULTS: The first 100 LSG and RA-LSG cases were separated to reflect the influence of learning curve. Mean length of hospital stay (LOS) was longer in RA-LSG patients at 1.3 +/- 0.6 days (range, 1-4), while it was 1.1 +/- 0.3 days (range, 1-2) in LSG patients. Thirty-day readmission rate was similar in both groups, 5.0 % in LSG and 6.0 % in RA-LSG group. One mortality (1.0 %) occurred in the RA-LSG group. In patients after 100 cases, mean LOS was still longer in RA LSG patients at 1.7 +/- 1.8 days (range, 1-21), while it was 1.2 +/- 0.5 days (range, 1-5) LSG patients. Thirty-day readmission rate and 30-day reoperation rate did not show a significant difference between the two groups. Overall leak rate was 3.2 % (n = 9) in LSG group, and 1.9 % (n = 5) in RA-LSG group, and the difference was not statistically significant. CONCLUSIONS: Our study showed similar 30-day readmission and reoperation rate between LSG and RA-LSG during the learning curve and after the proficiency has been achieved. PMID- 26992898 TI - Innate immune signaling through differential RIPK1 expression promote tumor progression in head and neck squamous cell carcinoma. AB - Head and neck squamous cell carcinoma (HNSCC) is a devastating disease for which new treatments, such as immunotherapy are needed. Synthetic double-stranded RNAs, which activate toll-like receptor 3 (TLR3), have been used as potent adjuvants in cancer immunotherapy by triggering a proapoptotic response in cancer cells. A better understanding of the mechanism of TLR3-mediated apoptosis and its potential involvement in controlling tumor metastasis could lead to improvements in current treatment. Using paired, autologous primary and metastatic HNSCC cells we previously showed that metastatic, but not primary tumor-derived cells, were unable to activate prosurvival NF-kappaB in response to p(I):p(C) resulting in an enhanced apoptotic response. Here, we show that transcriptional downregulation of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in metastatic HNSCC cells causes a loss of TLR3-mediated NF-kappaB signaling, resulting in enhanced apoptosis. Loss of RIPK1 strongly correlates with metastatic disease in a cohort of HNSCC patients. This downregulation of RIPK1 is possibly mediated by enhanced methylation of the RIPK1 promoter in tumor cells and enhances protumorigenic properties such as cell migration. The results described here establish a novel mechanism of TLR3-mediated apoptosis in metastatic cells and may create new opportunities for using double stranded RNA to target metastatic tumor cells. PMID- 26992900 TI - Oral intake of ranitidine increases urinary excretion of N-nitrosodimethylamine. AB - The H2-receptor antagonist, ranitidine, is among the most widely used pharmaceuticals to treat gastroesophageal reflux disease and peptic ulcers. While previous studies have demonstrated that amines can form N-nitrosamines when exposed to nitrite at stomach-relevant pH, N-nitrosamine formation from ranitidine, an amine-based pharmaceutical, has not been demonstrated under these conditions. In this work, we confirmed the production of N-nitrosodimethylamine (NDMA), a potent carcinogen, by nitrosation of ranitidine under stomach-relevant pH conditions in vitro We also evaluated the urinary NDMA excretion attributable to ingestion of clinically used ranitidine doses. Urine samples collected from five female and five male, healthy adult volunteers over 24-h periods before and after consumption of 150mg ranitidine were analyzed for residual ranitidine, ranitidine metabolites, NDMA, total N-nitrosamines and dimethylamine. Following ranitidine intake, the urinary NDMA excreted over 24h increased 400-folds from 110 to 47 600ng, while total N-nitrosamines increased 5-folds. NDMA excretion rates after ranitidine intake equaled or exceeded those observed previously in patients with schistosomiasis, a disease wherein N-nitrosamines are implicated as the etiological agents for bladder cancer. Due to metabolism within the body, urinary NDMA measurements represent a lower-bound estimate of systemic NDMA exposure. Our results suggest a need to evaluate the risks attributable to NDMA associated with chronic consumption of ranitidine, and to identify alternative treatments that minimize exposure to N-nitrosamines. PMID- 26992899 TI - Red meat and colorectal cancer: Nrf2-dependent antioxidant response contributes to the resistance of preneoplastic colon cells to fecal water of hemoglobin- and beef-fed rats. AB - Epidemiological studies have associated red meat intake with risk of colorectal cancer. Experimental studies explain this positive association by the oxidative properties of heme iron released in the colon. This latter is a potent catalyst for lipid peroxidation, resulting in the neoformation of deleterious aldehydes in the fecal water of heme-fed rats. The toxicity of fecal water of heme-fed rats was associated to such lipid peroxidation. This study demonstrated that fecal water of hemoglobin- and beef-fed rats preferentially induced apoptosis in mouse normal colon epithelial cells than in those carrying mutation on Apc (Adenomatous polyposis coli) gene, considered as preneoplastic. Highlighting the importance of lipid peroxidation and neoformation of secondary aldehydes like 4-hydroxy-2 nonenal (HNE), we optimized the depletion of carbonyl compounds in the fecal water which turned out to abolish the differential apoptosis in both cell lines. To explain the resistance of preneoplastic cells towards fecal water toxicity, we focused on Nrf2, known to be activated by aldehydes, including HNE. Fecal water activated Nrf2 in both cell lines, associated with the induction of Nrf2-target genes related to aldehydes detoxification. However, the antioxidant defense appeared to be higher in preneoplastic cells, favoring their survival, as evidenced by Nrf2 inactivation. Taken together, our results suggest that Nrf2 dependent antioxidant response was involved in the resistance of preneoplastic cells upon exposure to fecal water of hemoglobin- and beef-fed rats. This difference could explain the promoting effect of red meat and heme-enriched diet on colorectal cancer, by initiating positive selection of preneoplastic cells. PMID- 26992897 TI - Effects of Bariatric Surgery on Mortality, Cardiovascular Events, and Cancer Outcomes in Obese Patients: Systematic Review and Meta-analysis. AB - BACKGROUND: The long-term effects of bariatric surgery have yet to be established, and a number of important studies have recently emerged. This systematic review aimed to assess the effects of bariatric surgery on all-cause mortality, cardiovascular events, and cancer compared to non-surgical treatment. METHODS: We searched PubMed, EMBASE, and CENTRAL up to July 13, 2015, and included randomized controlled trials (RCTs) and non-randomized controlled studies comparing bariatric surgery versus non-surgical treatment and reporting data on the three defined outcomes at 1 year or longer. We analyzed RCTs and non randomized controlled studies, respectively. RESULTS: Eleven RCTs, 4 non randomized controlled trials, and 17 cohort studies were included. The randomized evidence suggested substantial uncertainty regarding the effects on all-cause mortality (0/382 vs. 1/287; 7 studies), cancer (OR 0.77, 95 % CI 0.22 to 2.71; 4 studies), and cardiovascular events (no data). The pooled adjusted estimates from non-randomized studies suggested that, compared to the control, the surgical group had lower risk of all-cause mortality (OR 0.55, 95 % CI 0.46 to 0.65; 10 studies), cancer (OR 0.74, 95 % CI 0.65 to 0.85; 2 studies), and cardiovascular events (MI: OR 0.71, 95 % CI 0.54 to 0.94; stroke: OR 0.66, 95 % CI 0.49 to 0.89; and their composite: OR 0.67, 95 % CI 0.54 to 0.83; 1 study). CONCLUSIONS: In conclusion, bariatric surgery could reduce all-cause mortality and probably reduce the risk of any type of cancer. The inference was, however, based on studies with limited methodological rigor. Uncertainty remains regarding the effects on cardiovascular events. PMID- 26992901 TI - Aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) polymorphisms exacerbate bladder cancer risk associated with alcohol drinking: gene-environment interaction. AB - Although a range of chemical exposures (cigarette smoking and occupational exposure) are recognized risk factors for the development of bladder cancer (BCa), many epidemiological studies have demonstrated that alcohol drinking is not associated with BCa risk. Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms impact the accumulation of acetaldehyde, resulting in an increased risk of various cancers. To date, however, no studies evaluating the association between BCa risk and alcohol drinking have considered these polymorphisms. Here, we conducted a matched case-control study to investigate whether ALDH2 and ADH1B polymorphisms influence BCa risk associated with alcohol drinking. Cases were 74 BCa patients and controls were 740 first-visit outpatients without cancer at Aichi Cancer Center Hospital between January 2001 and December 2005. Odds ratio (OR), 95% confidence interval (CI) and gene-environment interaction were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results showed that ALDH2 Glu/Lys was associated with a significantly increased risk of BCa compared with Glu/Glu (OR 2.03, 95% CI 1.14 3.62, P = 0.017). In contrast, ALDH2 Glu/Lys showed no increase in risk among the stratum of never drinkers compared with Glu/Glu, indicating a gene-environment interaction. ADH1B His/Arg had an OR of 1.98 (1.20-3.24, P = 0.007) compared with His/His. ADH1B Arg+ showed a similar OR and 95% CI. Individuals with ALDH2 Glu/Lys and ADH1B Arg+ had the highest risk of BCa compared with ALDH2 Glu/Glu and ADH1B His/His [OR 4.00 (1.81-8.87), P = 0.001]. PMID- 26992902 TI - Multipesticide residue levels in UHT and raw milk samples by GC-MUECD after QuEChER extraction method. AB - In the present study, milk samples including raw and ultra-high temperature (UHT) processed milk were analyzed for pesticide residue levels, including five pesticides, viz chloripyrifos, endosulfan (alpha and beta), profenofos and bifenthrin by gas chromatography microelectron capture detector (GC-MUECD) after extraction by QuEChERS method. Further confirmation of the pesticide residue was done by GC-MS. The pesticide residual level in raw and UHT milk samples (n = 70) was determined in the range of 0.1-30 MUg L(-1). All UHT processed milk samples contain pesticide residues within permissible limit set by the World Health Organization (WHO); however, among raw milk samples, chloripyrifos (12 %), alpha (24 %), and beta (14 %) endosulfan were found above the maximum residue limit (MRL). The estimated daily intake (EDI) of these four pesticide residues were also calculated as 1.32, 16.16, 5.30, 10.20, and 9.93 MUg kg(-1) body weight for chloripyrifos, endosulfan alpha, profenofos, endosulfan beta, and bifenthrin, respectively. It is concluded that the raw milk samples showed higher prevalence of pesticide residues as compared to UHT processed milk. Graphical abstract Determination of pesticide residues in dairy milk by GC-MUECD after QuEChERS extraction method. PMID- 26992903 TI - Fermentation of lignocellulosic sugars to acetic acid by Moorella thermoacetica. AB - A systematic study of bioconversion of lignocellulosic sugars to acetic acid by Moorella thermoacetica (strain ATCC 39073) was conducted. Four different water soluble fractions (hydrolysates) obtained after steam pretreatment of lignocellulosic biomass were selected and fermented to acetic acid in batch fermentations. M. thermoacetica can effectively ferment xylose and glucose in hydrolysates from wheat straw, forest residues, switchgrass, and sugarcane straw to acetic acid. Xylose and glucose were completely utilized, with xylose being consumed first. M. thermoacetica consumed up to 62 % of arabinose, 49 % galactose and 66 % of mannose within 72 h of fermentation in the mixture of lignocellulosic sugars. The highest acetic acid yield was obtained from sugarcane straw hydrolysate, with 71 % of theoretical yield based on total sugars (17 g/L acetic acid from 24 g/L total sugars). The lowest acetic acid yield was observed in forest residues hydrolysate, with 39 % of theoretical yield based on total sugars (18 g/L acetic acid from 49 g/L total sugars). Process derived compounds from steam explosion pretreatment, including 5-hydroxymethylfurfural (0.4 g/L), furfural (0.1 g/L) and total phenolics (3 g/L), did not inhibit microbial growth and acetic acid production yield. This research identified two major factors that adversely affected acetic acid yield in all hydrolysates, especially in forest residues: (i) glucose to xylose ratio and (ii) incomplete consumption of arabinose, galactose and mannose. For efficient bioconversion of lignocellulosic sugars to acetic acid, it is imperative to have an appropriate balance of sugars in a hydrolysate. Hence, the choice of lignocellulosic biomass and steam pretreatment design are fundamental steps for the industrial application of this process. PMID- 26992906 TI - Retraction Note to: TNF receptor-associated factor 6 regulates proliferation, apoptosis, and invasion of glioma cells. PMID- 26992904 TI - The epidemiology of antineutrophil cytoplasmic antibody-associated vasculitis in northwestern Turkey. AB - Epidemiological data about antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is very limited. Until now, there has been no study about the epidemiology of AAV in Turkey. In this study, we evaluated the frequency of AAV in the northeastern part of Turkey. The general clinical features of patients diagnosed with AAV at our center within the last 10 years (2004-2014) were retrospectively recorded down. The incidence rates and the prevalence per 1,000,000 population aged >=16 years were calculated. In addition, we evaluated the clinical features and survival rates of AAV patients. There were 30 patients with granulomatous polyangiitis (GPA), 15 with microscopic polyangiitis (MPA), and 5 with eosinophilic polyangiitis (EGPA). The overall prevalence of AAV in our region was 69.3/1,000,000 in individuals >=16 years. Males had a similar prevalence (73.2/1,000,000) with females (65.4/1,000,000). The mean annual incidence rate was 8.1/million for all AAV. The annual incidence of AAV in females was 6.9/million; in males, it was 9.2/million. The annual incidence for GPA was calculated as 4.8/1,000,000, the incidence for MPA was 2.4/1,000,000, and the incidence for CSS was 0.8/1,000,000. Ten-year survival of patients with AAV was 65.3 %. The only independent poor prognostic factor in Cox's multivariate analysis was advanced age at the time of diagnosis (OR 7.5, 95 % CI 10.6-526, p = 0.043). The frequency of all AAV in northwestern Turkey was similar to that in southern Europe; however, it was lower than the frequency in Northern Europe. PMID- 26992905 TI - Overexpression of HDAC9 promotes oral squamous cell carcinoma growth, regulates cell cycle progression, and inhibits apoptosis. AB - Histone deacetylases (HDACs) are a family of deacetylase enzymes that regulate the acetylation state of histones and a variety of other non-histone proteins including key oncogenic and tumor suppressor proteins, which modulates chromatin conformation, leading to regulation of gene expression. HDACs has been grouped into classes I-IV and histone deacetylase 9 (HDAC9) belongs to class IIa which exhibits tissue-specific expression. Recent reports have demonstrated both pro oncogenic and tumor suppressive role for HDAC9 in different cancers; however, its role in OSCC remains elusive. Here, we investigated the role of HDAC9 in pathogenesis of oral squamous cell carcinoma (OSCC). Our data showed significantly increased mRNA and protein expression of HDAC9 in clinical OSCC samples and UPCI-SCC-116 cells as compared to normal counterpart. Kaplan-Meier analysis showed that the patients with high-level of HDAC9 expression had significantly reduced overall survival than those with low-level of HDAC9 expression (p = 0.034). Knockdown of HDAC9 using siRNA interference suppressed cell proliferation, increased apoptosis, and induced G0/G1 cell cycle arrest in UPCI-SCC-116 cells. Immunofluorescence analysis showed increased nuclear localization of HDAC9 in frozen OSCC sections, and indicative of active HDAC9 that may transcriptionally repress its downstream target genes. Subsequent investigation revealed that overexpression of HDAC9 contributes to OSCC carcinogenesis via targeting a transcription factor, MEF2D, and NR4A1/Nur77, a pro-apoptotic MEF2 target. PMID- 26992908 TI - [The new German drug market law AMNOG from a child and adolescent psychiatry perspective]. AB - BACKGROUND: The European Union (EU) regulation 1901/2006 plus the implementation of pediatric investigational plans by the European Medicines Agency (EMA) have contributed to more clinical studies in pediatric psychopharmacology. A new drug market law (AMNOG) has been in force in Germany since 2011 that requires an additional process of assessment of benefits of newly authorized medications by the Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA), which also holds for medications licensed for pediatric populations. OBJECTIVES: Summary of early assessments of benefits for newly registered compounds in the treatment of psychiatric disorders and critical discussion from the perspective of child and adolescent psychiatry. MATERIAL AND METHODS: Application and critical review of documents and written statements by various institutions and stakeholders related to assessment procedures and respective decisions by the G-BA for these medications. RESULTS AND CONCLUSION: Clearly differing requirements for study designs and outcome parameters characterize the conditions for market authorization and for the assessment of benefits. Further adjustments to the regulations in implementing the AMNOG appear to be essential, integrating agencies involved so far, complimented by expertise from regulatory agencies and medical scientific societies. PMID- 26992907 TI - Expression and characterization of the SOS1 Arabidopsis salt tolerance protein. AB - SOS1 is the plasma membrane Na(+)/H(+) antiporter of Arabidopsis thaliana. It is responsible for the removal of intracellular sodium in exchange for an extracellular proton. SOS1 is composed of 1146 amino acids. Approximately 450 make the membrane domain, while the protein contains and a very large regulatory cytosolic domain of about 696 amino acids. Schizosaccharomyces pombe contains the salt tolerance Na(+)/H(+) antiporter proteins sod2. We examined the ability of SOS1 to rescue salt tolerance in S. pombe with a knockout of the sod2 gene (sod2::ura4). In addition, we characterized the importance of the regulatory tail of SOS1, in expression of the protein in S. pombe. We expressed full-length SOS1 and SOS1 shortened at the C-terminus and ending at amino acids 766 (medium) and 481 (short). The short version of SOS1 conveyed salt tolerance to sod2::ura4 yeast and Western blotting revealed that the protein was present. The protein was also targeted to the plasma membrane. The medium and full-length SOS1 protein were partially degraded and were not as well expressed as the short version of SOS1. The SOS1 short protein was also able to reduce Na(+) content in S. pombe. The full-length SOS1 dimerized and depended on the presence of the cytosolic tail. An analysis of SOS1 predicted a topology of 13 transmembrane segments, distinct from E. coli NhaA but similar to the Na(+)/H(+) exchangers Methanocaldococcus jannaschii NhaP1 and Thermus thermophile NapA. PMID- 26992910 TI - T2 map signal variation predicts symptomatic osteoarthritis progression: data from the Osteoarthritis Initiative. AB - OBJECTIVE: The aim of this work is to use quantitative magnetic resonance imaging (MRI) to identify patients at risk for symptomatic osteoarthritis (OA) progression. We hypothesized that classification of signal variation on T2 maps might predict symptomatic OA progression. METHODS: Patients were selected from the Osteoarthritis Initiative (OAI), a prospective cohort. Two groups were identified: a symptomatic OA progression group and a control group. At baseline, both groups were asymptomatic (Western Ontario and McMaster Universities Arthritis [WOMAC] pain score total <10) with no radiographic evidence of OA (Kellgren-Lawrence [KL] score <= 1). The OA progression group (n = 103) had a change in total WOMAC score greater than 10 by the 3-year follow-up. The control group (n = 79) remained asymptomatic, with a change in total WOMAC score less than 10 at the 3-year follow-up. A classifier was designed to predict OA progression in an independent population based on T2 map cartilage signal variation. The classifier was designed using a nearest neighbor classification based on a Gaussian Mixture Model log-likelihood fit of T2 map cartilage voxel intensities. RESULTS: The use of T2 map signal variation to predict symptomatic OA progression in asymptomatic individuals achieved a specificity of 89.3 %, a sensitivity of 77.2 %, and an overall accuracy rate of 84.2 %. CONCLUSION: T2 map signal variation can predict symptomatic knee OA progression in asymptomatic individuals, serving as a possible early OA imaging biomarker. PMID- 26992909 TI - MRI of the anterior talofibular ligament, talar cartilage and os subfibulare: Comparison of isotropic resolution 3D and conventional 2D T2-weighted fast spin echo sequences at 3.0 T. AB - PURPOSE: To determine the accuracy of a three-dimensional (3D) T2-weighted fast spin-echo (FSE) magnetic resonance (MR) sequence compared with two-dimensional (2D) sequence for diagnosing anterior talofibular ligament (ATFL) tears, chondral lesion of the talus (CLT) and os subfibulare/avulsion fracture of the distal fibula (OSF). MATERIALS AND METHODS: Thirty-five patients were included, who had undergone ankle MRI with 3D T2-weighted FSE and 2D T2-weighted FSE sequences, as well as subsequent ankle arthroscopy, between November 2013 and July 2014. Each MR imaging sequence was independently scored by two readers retrospectively for the presence of ATFL tears, CLT and OSF. The area under the receiver operating curve (AUC) was compared to determine the discriminatory power of the two image sequences. Interobserver agreement was expressed as unweighted kappa value. RESULTS: Arthroscopic findings confirmed 21 complete tears of the ATFL, 14 partial tears of the ATFL, 17 CLTs and 7 OSFs. There were no significant differences in the diagnoses of ATFL tears (p = 0.074-0.501), CLT (p = 0.090 0.450) and OSF (p = 0.317) obtained from the 2D and 3D sequences by either reader. The interobserver agreement rates between two readers using the 3D T2 weighted FSE sequence versus those obtained with the 2D sequence were substantial (kappa = 0.659) versus moderate (kappa = 0.553) for ATFL tears, moderate (kappa = 0.499) versus substantial (kappa = 0.676) for CLT and substantial (kappa = 0.621) versus substantial (kappa = 0.689) for OSF. CONCLUSION: Three-dimensional isotropic T2-weighted FSE MRI of the ankle resulted in no statistically significant difference in diagnostic performance compared to two-dimensional T2 weighted FSE MRI in the evaluation of ATFL tears, CLTs and OSFs. PMID- 26992912 TI - A new screening method for multidirectional shoulder instability on magnetic resonance arthrography: labro-capsular distance. AB - OBJECTIVE: To compare the capsular dimension as measured on magnetic resonance arthrography (MRA) between patients with multidirectional instability (MDI) of the shoulder and control subjects without instability. Ultimately, we aimed to develop an easy and reliable new screening method to assess MDI of the shoulder using MRA. MATERIALS AND METHODS: MRA images of patients with MDI of the shoulder (n = 25) during a 6-year period (February 2010 to May 2015) were retrospectively reviewed. A control group (n = 26) without instability was also identified. The capsular area was measured using a new screening method we termed labro-capsular (LC) distance. MRA images of the two groups were randomly mixed, and two orthopedic surgeon reviewers recorded anterior, posterior, and inferior LC distance measurements on axial and coronal images using a mid-glenoid cut. RESULTS: The inferior LC distance increased significantly in the patient group versus control group (P < 0.001), but there were no statistically significant differences in the anterior (P = 0.1165) and posterior (P = 0.5229) LC distances. An inferior LC distance >16.88 mm is most suggestive of MDI of the shoulder because of its high sensitivity (76 %) and specificity (96 %). CONCLUSION: The inferior LC distance can be easily and quickly measured and used as an effective clinical screening method for atraumatic MDI of the shoulder. PMID- 26992913 TI - Horizontal Gene Acquisitions, Mobile Element Proliferation, and Genome Decay in the Host-Restricted Plant Pathogen Erwinia Tracheiphila. AB - Modern industrial agriculture depends on high-density cultivation of genetically similar crop plants, creating favorable conditions for the emergence of novel pathogens with increased fitness in managed compared with ecologically intact settings. Here, we present the genome sequence of six strains of the cucurbit bacterial wilt pathogen Erwinia tracheiphila (Enterobacteriaceae) isolated from infected squash plants in New York, Pennsylvania, Kentucky, and Michigan. These genomes exhibit a high proportion of recent horizontal gene acquisitions, invasion and remarkable amplification of mobile genetic elements, and pseudogenization of approximately 20% of the coding sequences. These genome attributes indicate that E. tracheiphila recently emerged as a host-restricted pathogen. Furthermore, chromosomal rearrangements associated with phage and transposable element proliferation contribute to substantial differences in gene content and genetic architecture between the six E. tracheiphila strains and other Erwinia species. Together, these data lead us to hypothesize that E. tracheiphila has undergone recent evolution through both genome decay (pseudogenization) and genome expansion (horizontal gene transfer and mobile element amplification). Despite evidence of dramatic genomic changes, the six strains are genetically monomorphic, suggesting a recent population bottleneck and emergence into E. tracheiphila's current ecological niche. PMID- 26992914 TI - Visualization of the Biological Behavior of Tumor-Associated Macrophages in Living Mice with Colon Cancer Using Multimodal Optical Reporter Gene Imaging. AB - We sought to visualize the migration of tumor-associated macrophages (TAMs) to tumor lesions and to evaluate the effects of anti-inflammatory drugs on TAM modulated tumor progression in mice with colon cancer using a multimodal optical reporter gene system. Murine macrophage Raw264.7 cells expressing an enhanced firefly luciferase (Raw/effluc) and murine colon cancer CT26 cells coexpressing Rluc and mCherry (CT26/Rluc-mCherry, CT26/RM) were established. CT26/RM tumor bearing mice received Raw/effluc via their tail veins, and combination of bioluminescence imaging (BLI) and fluorescence imaging (FLI) was conducted for in vivo imaging of TAMs migration and tumor progression. Dexamethasone (DEX), a potent anti-inflammatory drug, was administered intraperitoneally to tumor bearing mice following the intravenous transfer of Raw/effluc cells. The migration of TAMs and tumor growth was monitored by serial FLI and BLI. The migration of Raw/effluc cells to tumor lesions was observed at day 1, and BLI signals were still distinct at tumor lesions on day 4. Localization of BLI signals from migrated Raw/effluc cells corresponded to that of FLI signals from CT26/RM tumors. In vivo FLI of tumors demonstrated enhanced tumor growth associated with macrophage migration to tumor lesions. Treatment with DEX inhibited the influx of Raw/effluc cells to tumor lesions and abolished the enhanced tumor growth associated with macrophage migration. These findings suggest that molecular imaging approach for TAM tracking is a valuable tool for evaluating the role of TAMs in the tumor microenvironment as well as for the development of new drugs to control TAM involvement in the modulation of tumor progression. PMID- 26992915 TI - Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages. AB - Pancreatic cancer is characterized by an extensive desmoplastic stroma, the functional relevance of which is poorly understood. Activated fibroblasts are a prevalent component of the stroma, and traditionally, these cells have been considered as a homogenous population derived from pancreatic stellate cells. In this study, we highlight a previously unappreciated heterogeneity of the fibroblast population within the stroma. In particular, a subset of stromal fibroblasts has characteristics of mesenchymal stem cells (MSCs). MSCs are present in the normal pancreas as well as in the carcinomatous pancreas (CA MSCs). Here, we determine that CA-MSCs have increased tumor-promoting function compared with MSCs in normal pancreas. This ability to promote tumor growth is associated with CA-MSCs' unique ability to promote alternative macrophage polarization. Thus, our study identifies a previously uncharacterized cell population within the stroma and sheds light on tumor-promoting interactions between different components of the stroma. SIGNIFICANCE: Targeting the stroma is emerging as a new paradigm in pancreatic cancer; however, efforts to that effect are hampered by our limited understanding of the nature and function of stromal components. Here, we uncover previously unappreciated heterogeneity within the stroma and identify interactions among stromal components that promote tumor growth and could be targeted therapeutically. PMID- 26992916 TI - Rat Prostate Tumor Cells Progress in the Bone Microenvironment to a Highly Aggressive Phenotype. AB - Prostate cancer generally metastasizes to bone, and most patients have tumor cells in their bone marrow already at diagnosis. Tumor cells at the metastatic site may therefore progress in parallel with those in the primary tumor. Androgen deprivation therapy is often the first-line treatment for clinically detectable prostate cancer bone metastases. Although the treatment is effective, most metastases progress to a castration-resistant and lethal state. To examine metastatic progression in the bone microenvironment, we implanted androgen sensitive, androgen receptor-positive, and relatively slow-growing Dunning G (G) rat prostate tumor cells into the tibial bone marrow of fully immune-competent Copenhagen rats. We show that tumor establishment in the bone marrow was reduced compared with the prostate, and whereas androgen deprivation did not affect tumor establishment or growth in the bone, this was markedly reduced in the prostate. Moreover, we found that, with time, G tumor cells in the bone microenvironment progress to a more aggressive phenotype with increased growth rate, reduced androgen sensitivity, and increased metastatic capacity. Tumor cells in the bone marrow encounter lower androgen levels and a higher degree of hypoxia than at the primary site, which may cause high selective pressures and eventually contribute to the development of a new and highly aggressive tumor cell phenotype. It is therefore important to specifically study progression in bone metastases. This tumor model could be used to increase our understanding of how tumor cells adapt in the bone microenvironment and may subsequently improve therapy strategies for prostate metastases in bone. PMID- 26992917 TI - Elucidation of Resistance Mechanisms to Second-Generation ALK Inhibitors Alectinib and Ceritinib in Non-Small Cell Lung Cancer Cells. AB - Crizotinib is the first anaplastic lymphoma kinase (ALK) inhibitor to have been approved for the treatment of non-small cell lung cancer (NSCLC) harboring an ALK fusion gene, but it has been found that, in the clinic, patients develop resistance to it. Alectinib and ceritinib are second-generation ALK inhibitors which show remarkable clinical responses in both crizotinib-naive and crizotinib resistant NSCLC patients harboring an ALK fusion gene. Despite their impressive activity, clinical resistance to alectinib and ceritinib has also emerged. In the current study, we elucidated the resistance mechanisms to these second-generation ALK inhibitors in the H3122 NSCLC cell line harboring the EML4-ALK variant 1 fusion in vitro. Prolonged treatment of the parental H3122 cells with alectinib and ceritinib led to two cell lines which are 10 times less sensitive to alectinib and ceritinib than the parental H3122 cell line. Although mutations of ALK in its kinase domain are a common resistance mechanism for crizotinib, we did not detect any ALK mutation in these resistant cell lines. Rather, overexpression of phospho-ALK and alternative receptor tyrosine kinases such as phospho-EGFR, phospho-HER3, and phospho-IGFR-1R was observed in both resistant cell lines. Additionally, NRG1, a ligand for HER3, is upregulated and responsible for resistance by activating the EGFR family pathways through the NRG1-HER3-EGFR axis. Combination treatment with EGFR inhibitors, in particular afatinib, was shown to be effective at overcoming resistance. Our study provides new mechanistic insights into adaptive resistance to second-generation ALK inhibitors and suggests a potential clinical strategy to combat resistance to these second generation ALK inhibitors in NSCLC. PMID- 26992918 TI - Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation. AB - The current paradigm of pancreatic neoplastic transformation proposes an initial step whereby acinar cells convert into acinar-to-ductal metaplasias, followed by progression of these lesions into neoplasias under sustained oncogenic activity and inflammation. Understanding the molecular mechanisms driving these processes is crucial to the early diagnostic and prevention of pancreatic cancer. Emerging evidence indicates that transcription factors that control exocrine pancreatic development could have either, protective or facilitating roles in the formation of preneoplasias and neoplasias in the pancreas. We previously identified that the homeodomain transcription factor Prox1 is a novel regulator of mouse exocrine pancreas development. Here we investigated whether Prox1 function participates in early neoplastic transformation using in vivo, in vitro and in silico approaches. We found that Prox1 expression is transiently re-activated in acinar cells undergoing dedifferentiation and acinar-to-ductal metaplastic conversion. In contrast, Prox1 expression is largely absent in neoplasias and tumors in the pancreas of mice and humans. We also uncovered that Prox1-heterozygosis markedly increases the formation of acinar-to-ductal-metaplasias and early neoplasias, and enhances features associated with inflammation, in mouse pancreatic tissues expressing oncogenic Kras. Furthermore, we discovered that Prox1-heterozygosis increases tissue damage and delays recovery from inflammation in pancreata of mice injected with caerulein. These results are the first demonstration that Prox1 activity protects pancreatic cells from acute tissue damage and early neoplastic transformation. Additional data in our study indicate that this novel role of Prox1 involves suppression of pathways associated with inflammatory responses and cell invasiveness. PMID- 26992921 TI - Anti-osteoclastogenic effects of isoquinoline alkaloids from the rhizome extract of Sinomenium acutum. AB - A phytochemical investigation for the rhizome extract from Sinomenium acutum (Menispermaceae) resulted in the isolation of several active principles responsible for the anti-osteoclastogenic property of the extract, together with related isoquinoline alkaloids (1-13) including two new compounds, 1 and 2. Among isolated compounds, salutaridine (7), dauricumine (10), cheilanthifoline (12), and dauriporphine (13) were observed to give significant inhibitions on receptor activator of nuclear factor-kappaB ligand-induced differentiation of mouse bone marrow-derived macrophages into multinucleated osteoclasts, respectively. The chemical structures of two newly isolated compounds, 1 and 2 were established as 8-demethoxycephatonine (1) and 7(R)-7,8-dihydrosinomenine (2), by spectroscopic analyses including 2D NMR experiments. PMID- 26992919 TI - Regulation of Glioblastoma Tumor-Propagating Cells by the Integrin Partner Tetraspanin CD151. AB - Glioblastoma (GBM) stem cells (GSCs) represent tumor-propagating cells with stem like characteristics (stemness) that contribute disproportionately to GBM drug resistance and tumor recurrence. Understanding the mechanisms supporting GSC stemness is important for developing therapeutic strategies for targeting GSC dependent oncogenic mechanisms. Using GBM-derived neurospheres, we identified the cell surface tetraspanin family member CD151 as a novel regulator of glioma cell stemness, GSC self-renewal capacity, migration, and tumor growth. CD151 was found to be overexpressed in GBM tumors and GBM neurospheres enriched in GSCs. Silencing CD151 inhibited neurosphere forming capacity, neurosphere cell proliferation, and migration and attenuated the expression of markers and transcriptional drivers of the GSC phenotype. Conversely, forced CD151 expression promoted neurosphere self-renewal, cell migration, and expression of stemness associated transcription factors. CD151 was found to complex with integrins alpha3, alpha6, and beta1 in neurosphere cells, and blocking CD151 interactions with integrins alpha3 and alpha6 inhibited AKT phosphorylation, a downstream effector of integrin signaling, and impaired sphere formation and neurosphere cell migration. Additionally, targeting CD151 in vivo inhibited the growth of GBM neurosphere-derived xenografts. These findings identify CD151 and its interactions with integrins alpha3 and alpha6 as potential therapeutic targets for inhibiting stemness-driving mechanisms and stem cell populations in GBM. PMID- 26992922 TI - Effect of magnesium carbonate on the solubility, dissolution and oral bioavailability of fenofibric acid powder as an alkalising solubilizer. AB - To investigate the possibility of developing a novel oral pharmaceutical product using fenofibric acid instead of choline fenofibrate, the powder properties, solubility, dissolution and pharmacokinetics in rats of fenofibrate, choline fenofibrate and fenofibric acid were compared. Furthermore, the effect of magnesium carbonate, an alkalising agent on the solubility, dissolution and oral bioavailability of fenofibric acid was assessed, a mixture of fenofibric acid and magnesium carbonate being prepared by simple blending at a weight ratio of 2/1. The three fenofibrate derivatives showed different particle sizes and melting points with similar crystalline shape. Fenofibric acid had a significantly higher aqueous solubility and dissolution than fenofibrate, but significantly lower solubility and dissolution than choline fenofibrate. However, the fenofibric acid/magnesium carbonate mixture greatly improved the solubility and dissolution of fenofibric acid with an enhancement to levels similar with those for choline fenofibrate. Fenofibric acid gave lower plasma concentrations, AUC and Cmax values compared to choline fenofibrate in rats. However, the mixture resulted in plasma concentrations, AUC and Cmax values levels not significantly different from those for choline fenofibrate. Specifically, magnesium carbonate increased the aqueous solubility, dissolution and bioavailability of fenofibric acid by about 7.5-, 4- and 1.6-fold, respectively. Thus, the mixture of fenofibric acid and magnesium carbonate at the weight ratio of 2/1 might be a candidate for an oral pharmaceutical product with improved oral bioavailability. PMID- 26992920 TI - Drug-Induced Mitochondrial Toxicity. AB - The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These 'off-target' pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA. The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical 'weight loss' agent. The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy. PMID- 26992923 TI - Defects in Protein Folding Machinery Affect Cell Wall Integrity and Reduce Ethanol Tolerance in S. cerevisiae. AB - The chaperonin complex CCT/TRiC (chaperonin containing TCP-1/TCP-1 ring complex) participates in the folding of many crucial proteins including actin and tubulin in eukaryotes. Mutations in genes encoding its subunits can affect protein folding and in turn, the physiology of the organism. Stress response in Saccharomyces cerevisiae is important in fermentation reactions and operates through overexpression and underexpression of genes, thus altering the protein profile. Defective protein folding machinery can disturb this process. In this study, the response of cct mutants to stress conditions in general and ethanol in specific was investigated. CCT1 mutants showed decreased resistance to different conditions tested including osmotic stress, metal ions, surfactants, reducing and oxidising agents. Cct1-3 mutant with the mutation in the conserved ATP-binding region showed irreversible defects than other mutants. These mutants were found to have inherent cell wall defects and showed decreased ethanol tolerance. This study reveals that cell wall defects and ethanol sensitivity are linked. Genetic and proteomic analyses showed that the yeast genes RPS6A (ribosomal protein), SCL1 (proteasomal subunit) and TDH3 (glyceraldehyde-3-phosphate dehydrogenase) on overexpression, improved the growth of cct1-3 mutant on ethanol. We propose the breakdown of common stress response pathways caused by mutations in CCT complex and the resulting scarcity of functional stress-responsive proteins, affecting the cell's defence against different stress agents in cct mutants. Defective cytoskeleton and perturbed cell wall integrity reduce the ethanol tolerance in the mutants which are rescued by the extragenic suppressors. PMID- 26992924 TI - Errors in NOF meta-analyses of calcium and vitamin D supplements. PMID- 26992926 TI - Referees 2015. PMID- 26992925 TI - Re: Errors in the NOF meta-analysis of calcium and vitamin D supplements. PMID- 26992927 TI - Laparoscopic versus robotic right colectomy: technique and outcomes. AB - Minimally invasive surgery has gained worldwide acceptance in the treatment of colonic cancer in the last decades, thanks to its well-known advantages in short term outcomes. Nevertheless, the penetrance of minimally invasive colorectal surgery still remains low. Few studies and metanalysis, to date, have analyzed the results of robotic versus laparoscopic colorectal surgery, often with conflicting conclusions. The robotic platform, thanks to its technological features, may potentially overcome the limitation of standard laparoscopy, especially when performing a complete mesocolic excision resection and an intracorporeal anastomosis. Robotic surgery could also shorten the learning curve of young novice surgeons, provided that strict protocols of structured training are applied. This paper is an update on the current available outcomes of robotic vs laparoscopic surgery in right colectomy. PMID- 26992928 TI - Mitochondrial signaling in the vascular endothelium: beyond reactive oxygen species. AB - Traditionally, the mitochondria have been viewed as the cell's powerhouse, producing energy in the form of ATP. As a byproduct of ATP formation, the mitochondrial electron transport chain produces substantial amounts of reactive oxygen species (ROS). First thought to be toxic, recent literature indicates an important signaling function for mitochondria-derived ROS, especially in relation to cardiovascular disease pathogenesis. This has spawned an evolution to a more contemporary view of mitochondrial function as a dynamic organelle involved in key regulatory and cell survival processes. Beyond ROS, recent studies have identified a host of mitochondria-linked factors that influence the cellular and extracellular environments, including mitochondria-derived peptides, mitochondria localized proteins, and the mitochondrial genome itself. Interestingly, many of these factors help orchestrate ROS homeostasis and ROS-related signaling. The paradigm defining the role of mitochondria in the vasculature needs to be updated yet again to include these key signaling factors, which serves as the focus of the current review. In describing these novel signaling factors, we pay specific attention to their influence on endothelial homeostasis. Therapies targeting these pathways are discussed, as are emerging research directions. PMID- 26992929 TI - Antipsychotic medications for cocaine dependence. AB - BACKGROUND: Cocaine dependence is a public health problem characterised by recidivism and a host of medical and psychosocial complications. Cocaine dependence remains a disorder for which no pharmacological treatment of proven efficacy exists. OBJECTIVES: To evaluate the efficacy and the acceptability of antipsychotic medications for cocaine dependence. SEARCH METHODS: This review is an update of a previous Cochrane review published in 2007. We searched up to 15 July 2015 in Cochrane Drugs and Alcohol Group Specialised Register (searched in CRSLive); the Cochrane Library (including the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE)); PubMed; EMBASE; CINAHL and Web of Science. All searches included non English language literature. SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials with focus on the use of any antipsychotic medication for the treatment of cocaine dependence. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 studies (719 participants). The antipsychotic drugs studied were risperidone, olanzapine, quetiapine, lamotrigine, aripiprazol, haloperidol and reserpine. Comparing any antipsychotic drugs versus placebo, we found that antipsychotics reduced dropout: eight studies, 397 participants, risk ratio (RR) 0.75 (95% confidence interval (CI) 0.57 to 0.97), moderate quality of evidence. We found no significant differences for any of the other primary outcomes considered: number of participants using cocaine during the treatment, two studies, 91 participants: RR 1.02 (95% CI 0.65 to 1.62); continuous abstinence, three studies, 139 participants: RR 1.30 (95% CI 0.73 to 2.32); side effects, six studies, 291 participants: RR 1.01 (95% CI 0.93 to 1.10); and craving, four studies, 240 participants: RR 0.13 (-1.08 to 1.35). For all of these comparisons we rated the quality of evidence as low.Comparisons of single drug versus placebo or versus another drug are conducted in few trials with small sample sizes, limiting the reliability of the results. Among these comparisons, only quetiapine seemed to outperform placebo in reducing cocaine use, measured by grams per week: mean difference (MD) -0.54 (95% CI -0.92 to -0.16), by US dollars spent per week: MD -53.80 (95% CI -97.85 to -9.75), and by craving: MD -1.23 (95% CI -2.19 to 0.27), but results came from one study with 60 participants.The major limitations of the studies were the high risk of attrition bias (40% of the included studies) and low quality of reporting, mainly for the risk of selection bias, performance and detection bias, that we rated as being at unclear risk for 75% to 80% of the studies. Furthermore, most of the included studies did not report results on important outcomes such as side effects, or use of cocaine during treatment and craving, which prevented the possibility of including them in statistical synthesis. AUTHORS' CONCLUSIONS: At present, there is no evidence supporting the clinical use of antipsychotic medications in the treatment of cocaine dependence, although results come from only 14 trials, with small sample sizes and moderate to low quality of evidence. PMID- 26992931 TI - Smoking prevalence among pregnant women from 2007 to 2012 at a tertiary-care hospital. AB - The harmful effects of smoking during pregnancy are well known, but we lack prevalence data concerning this subject in Austria. The aim ofz the present study was to determine the prevalence and any changes in the prevalence of smoking during pregnancy in the last few years. The investigation was conducted at a perinatal center in Vienna, Austria. Further aims of the study were to evaluate maternal characteristics associated with smoking and demonstrate the harmful effects of smoking on neonatal outcome in this population. Once inquired, self reported smoking during pregnancy, maternal age, and neonatal data from 2007 to 2012 were evaluated retrospectively. Of birth records, 11,142 were analyzed. From 2007 to 2012, the prevalence of smoking declined significantly from 19.1 to 15.6 %. The overall prevalence was 18.1 % and was highest (43.7 %) among young women (<20 years). The risk of small for gestational age (SGA) was significantly higher among newborns of smoking mothers. CONCLUSION: The prevalence of smoking among pregnant women has declined in Austria in the last few years but is still quite high. Prevention programs should focus on young women, who are at highest risk in this regard. WHAT IS KNOWN: * Smoking during pregnancy is known to exert harmful effects What is New: * Paucity of epidemiological data regarding this subject in Austria * Significant decline of self-reported smoking during pregnancy from 2007 to 2012 in Vienna. PMID- 26992930 TI - Central Parkin: The evolving role of Parkin in the heart. AB - Parkin is familiar to many because of its link to Parkinson's disease, and to others because of its well-characterized role as a central factor mediating selective mitophagy of damaged mitochondria for mitochondrial quality control. The genetic connection between Parkin and Parkinson's disease derives from clinical gene-association studies, whereas our mechanistic understanding of Parkin functioning in mitophagy is based almost entirely on work performed in cultured cells. Surprisingly, experimental evidence linking the disease and the presumed mechanism derives almost entirely from fruit flies; germline Parkin deficient mice do not develop Parkinson's disease phenotypes. Moreover, genetic manipulation of Parkin signaling in mouse hearts does not support a central role for Parkin in homeostatic mitochondrial quality control in this mitochondria-rich and -dependent organ. Here, I provide an overview of data suggesting that (in mouse hearts at least) Parkin functions more as a stress-induced and developmentally-programmed facilitator of cardiomyocyte mitochondrial turnover. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016. PMID- 26992932 TI - Answer to the Letter to the Editor of Hao Liu et al. concerning "The application of zero-profile anchored spacer in anterior cervical discectomy and fusion" by Wang et al. Eur Spine J. 2015 Jan; 24(1):148-54. doi:10.1007/s00586-014-3628-9. PMID- 26992933 TI - Apparent diffusion coefficient in the evaluation of side-specific extracapsular extension in prostate cancer: Development and external validation of a nomogram of clinical use. AB - OBJECTIVES: The aim of this study is to develop a nomogram of clinical utility based on apparent diffusion coefficient (ADC) from diffusion-weighted imaging to predict extracapsular extension (ECE), and to validate externally its clinical utility. MATERIALS AND METHODS: A total of 101 men (70 for the creation and 31 for external validation of the nomogram) underwent 1.5T multiparametric magnetic resonance imaging followed by radical prostatectomy at 2 different institutions. ADC values were assessed for normal and pathological tissue. Clinical and pathological variables were investigated by univariate and multivariate logistic regression analyses on 70 patients and logistic regression coefficients were used to develop our nomogram. Receiver operating characteristic curve analysis was performed to determine the optimal ADC cut off for ECE. The nomogram was then externally validated on 31 patients at another institution. RESULTS: At univariate analysis, the following variables were associated with ECE: pathological ADC and Gleason at biopsy (P<0.001) along with tumor volume and ECE at imaging (P = 0.003). At multivariate analysis, pathological ADC (P = 0.027), tumor volume (P = 0.011), and biopsy Gleason (P = 0.040) maintained their independent predictor status and were included in our nomogram together with normal ADC and ECE at imaging. Our nomogram showed a significant higher sensitivity (88%) than T2-weighted imaging (54%; P = 0.010). External validation resulted in an overall accuracy of 81%. CONCLUSIONS: ADC represents a potential imaging biomarker to predict side-specific ECE in patients with prostate cancer. Our nomogram could improve the current diagnostic pathway and possibly the therapeutic approach for this disease. PMID- 26992934 TI - Identifying the emerging role of adipokine as a diagnostic and prognostic biomarker of renal cell carcinoma. AB - OBJECTIVE: To assess the association and prognostic value of adipokines (adipocyte-secreted peptide hormones) in renal cell carcinoma (RCC). MATERIALS AND METHODS: Plasma samples from 54 RCC patients and 25 age-matched healthy controls were analyzed for levels of adipokines (adiponectin, leptin, retinol binding protein 4 [RBP4], and nicotinamide phosphoribosyltransferase [NAMPT]). Baseline characteristics and adipokine levels were compared between patients and controls. The effect of adipokine levels on RCC severity was also investigated. RESULTS: Medians (patients/controls) were body mass index: 24.6/23.5kg/m(2), serum glucose: 111/93mg/dl, and high-density lipoprotein: 43/53mg/dl, and significantly differed between the 2 groups. Median levels (patients/controls) of adipokines were adiponectin: 4.36/8.84ug/ml, leptin: 2.91/2.92ng/ml, RBP4: 30.27/16.17ug/ml and NAMPT: 2.26/2.06ng/ml; adiponectin, RBP4 and NAMPT (but not leptin) were independently associated with RCC in logistic regression models, and only serum NAMPT was significantly associated with RCC severity (T stage). CONCLUSIONS: Lower plasma levels of adiponectin, and higher levels of RBP4 and NAMPT, are strongly correlated with RCC, indicating that these adipokines could be used as biomarkers for RCC. PMID- 26992935 TI - Robotic Single-Site and Conventional Laparoscopic Surgery in Gynecology: Clinical Outcomes and Cost Analysis of a Matched Case-Control Study. AB - STUDY OBJECTIVE: To assess the clinical outcomes and costs associated with robotic single-site (RSS) surgery compared with those of conventional laparoscopy (CL) in gynecology. DESIGN: Retrospective case-control study (Canadian Task Force classification II-2). SETTING: University-affiliated community hospital. PATIENTS: Female patients undergoing RSS or CL gynecologic procedures. INTERVENTIONS: Comparison of consecutive RSS gynecologic procedures (cases) undertaken between October 2013 and March 2014 with matched CL procedures (controls) completed during the same time period by the same surgeon. MEASUREMENTS AND MAIN RESULTS: Patient demographic data, operative data, and hospital financial data were abstracted from the electronic charts and financial systems. An incremental cost analysis based on the use of disposable equipment was performed. Total hospital charges were determined for matched RSS cases vs CL cases. RSS surgery was completed in 25 out of 33 attempts; 3 cases were aborted before docking, and 5 were converted to a multisite surgery. There were no intraoperative complications or conversions to laparotomy. The completed cases included 11 adnexal cases and 14 hysterectomies, 3 of which included pelvic lymph node dissection. Compared with the CL group, total operative times were higher in the RSS group; however, there were no significant between-group differences in estimated blood loss, length of hospital stay, or complication rates. Disposable equipment cost per case, direct costs, and total hospital charges were evaluated. RSS was associated with an increased disposable cost per case of $248 to $378, depending on the method used for vaginal cuff closure. The average total hospital charges for matched outpatient adnexal surgery were $15,450 for the CL controls and $18,585 for the RSS cases (p < .001), and the average total hospital charges for matched outpatient benign hysterectomy were $14,623 for the CL controls and $21,412 for the RSS cases (p < .001). CONCLUSION: Although RSS surgery and CL have comparable clinical outcomes in selected patients, RSS surgery remains associated with increased incremental disposable cost per case and total hospital charges. Careful case selection and judicious use of equipment are necessary to maximize cost-effectiveness in RSS gynecologic surgery. PMID- 26992936 TI - Water consumption and urinary tract infections: an in vitro study. AB - OBJECTIVES: To address to a better understanding of whether increased water consumption is associated with beneficial effects of urinary tract infections prophylaxis and treatment, and if so, the mechanism involved in this process. METHODS: Models of the catheterized bladder were infected with Escherichia coli. Artificial urine was supplied at various flow rates and various concentrations to separately assess the "flushing effect" and "dilution effect" of increased water consumption on catheter blockage time, encrustation formation, and bacterial growth. RESULTS: There were no statistical significances regarding catheter blockage time (P = 0.92), encrustation formation, and bacterial growth among bladder models supplied with various flow rates. When the flow rate was set as 1 ml/min, however, there showed significant decrease trend of the time to blockage (P = 0.0005), encrustation formation, and bacterial growth as the concentration of the artificial urine increased except the twofold-concentration urine group. CONCLUSIONS: Increased water consumption is associated with beneficial effects of urinary tract infection prophylaxis and treatment, and dilution effect of bacteria nutrition in the urine is at least partly involved in this process if not all, rather than the "flushing effect". Considering the flaws and the in vitro design of the current study, however, an in vivo study is warranted. PMID- 26992937 TI - The effects of passive leg raising and ultrafiltration stopping on blood pressure in hemodialysis patients. AB - PURPOSE: Hemodialysis-associated hypotension, one of the more serious issues in hemodialysis patients, can be treated by passive leg raising (PLR) and ultrafiltration (UF) stopping. We investigated the effects of PLR and UF stopping on blood pressure in hemodialysis patients. METHODS: The study was conducted in 76 end-stage renal disease patients. After the second hour of dialysis, systolic and diastolic blood pressure (SBP and DBP) of the patients who did not develop intradialytic hypotension (IDH) were measured in the supine position. Thereafter, PLR was performed by raising the legs 20 degrees ; and after 3 min, SBP and DBP were measured again. UF was then stopped in the PLR position; SBP and DBP were repeated 3 min later. The same procedure was performed during IDH in the patients that developed IDH. RESULTS: A mean 5-mmHg (p < 0.05) increase in SBP and a mean 2-mmHg increase in DBP (p < 0.05) were observed by PLR in the supine position. UF stopping during PLR increased SBP by a mean of 1 mmHg (p < 0.05) while no change was observed in DBP (p = ns). IDH occurred in 19 (25 %) patients. PLR positioning increases SBP and DBP by a mean of 8 mmHg (p < 0.05) and 3 mmHg (p < 0.05), respectively, in the supine position during IDH. During IDH, UF stopping in the PLR position did not significantly increase SBP and DBP in patients as compared to the PLR position. CONCLUSIONS: SBP and DBP increase during PLR. UF stopping during PLR does not lead to a higher increase in blood pressure as compared to PLR positioning. PMID- 26992938 TI - The role of the temporal pole in modulating primitive auditory memory. AB - Primitive auditory memory (PAM), which is recognized as the early point in the chain of the transient auditory memory system, faithfully maintains raw acoustic fine-structure signals for up to 20-30 milliseconds. The neural mechanisms underlying PAM have not been reported in the literature. Previous anatomical, brain-imaging, and neurophysiological studies have suggested that the temporal pole (TP), part of the parahippocampal region in the transitional area between perirhinal cortex and superior/inferior temporal gyri, is involved in auditory memories. This study investigated whether the TP plays a role in mediating/modulating PAM. The longest interaural interval (the interaural-delay threshold) for detecting a break in interaural correlation (BIC) embedded in interaurally correlated wideband noises was used to indicate the temporal preservation of PAM and examined in both healthy listeners and patients receiving unilateral anterior temporal lobectomy (ATL, centered on the TP) for treating their temporal lobe epilepsy (TLE). The results showed that patients with ATL were still able to detect the BIC even when an interaural interval was introduced, regardless of which ear was the leading one. However, in patient participants, the group-mean interaural-delay threshold for detecting the BIC under the contralateral-ear-leading (relative to the side of ATL) condition was significantly shorter than that under the ipsilateral-ear-leading condition. The results suggest that although the TP is not essential for integrating binaural signals and mediating the PAM, it plays a role in top-down modulating the PAM of raw acoustic fine-structure signals from the contralateral ear. PMID- 26992940 TI - Interactions Between Children and Pediatric Nurses at the Emergency Department: A Swedish Interview Study. AB - Admission to an emergency department can be considered a stressful event for both the child and the family. Due to the nature of traumas, illnesses and fatalities it is a chaotic forum in which good communication between child and staff can be difficult to establish. PURPOSE: The purpose of the study was to describe nurses' methods when interacting with children aged three to six at a pediatric emergency department and to identify aspects in need of further investigation. METHODS: The study included seven nurses who work with children. The data were collected through semi-structured interviews and analyzed using qualitative content analysis. RESULTS: The analysis resulted in three main themes; fundamentals for being able to create a good encounter, nurse's adaptations when encountering children and limitations associated with providing child and family-centered care in the pediatric emergency department. CONCLUSIONS: Healthcare organizations must create time to allow important communication to take place between staff and pediatric patients so that children and families feel safe when being treated. The implementation of effective measures to train staff in communication with pediatric patients is important. PRACTICE IMPLICATIONS: The child should participate in his/her care and in procedures as much as possible. By listening to children and their parents proposals, especially before invasive procedures, effective ways to handle pain and discomfort may be developed. PMID- 26992939 TI - Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats. AB - In the clinical setting, the use of QX-314 (a quaternary derivative of lidocaine) has been proposed to achieve the selective inhibition of nociceptors that express transient receptor potential vanilloid 1 (TRPV1) channels with fewer motor deficits. However, it has been also reported that QX-314 may produce systemic CNS toxicities with relative potencies that are approximately twice as high as those of lidocaine. There are no reports concerning the effects of extracellular QX-314 on the rhythm-generating neurons in the respiratory center. In the present study, we examined the effects of QX-314 on respiratory rhythm generation in brainstem spinal cord preparations from newborn rats. The extracellular application of QX 314 (200MUM) decreased the C4 burst rate, amplitude and slope during the initial rising phase, and the effects slowly developed with a half-decay time of approximately 20min. The combined application of capsaicin (10 or 100MUM) with QX 314 (100MUM) showed no additional effect. The intracellular application of QX-314 (100MUM) to respiratory neurons depressed the action potentials with a half-decay time of around 5min. Our findings could explain one of the mechanisms underlying the central toxicities that occur after the systemic application of QX-314. PMID- 26992941 TI - Exclusion of Residents From Surgery-Intensive Care Team Communication: A Qualitative Study. AB - OBJECTIVE: Communication competency is an important aspect of postgraduate training and patient care delivery in all specialties and clinical domains. This study explored staff surgeon and intensivist perceptions of and experiences with residents' communication with a view toward fostering high quality interspecialty team communication in the surgical intensive care unit. DESIGN: A qualitative study using semistructured interviews. Data were analyzed iteratively and inductively as per standard qualitative thematic approach. SETTING: University of Toronto, Toronto, Canada. PARTICIPANTS: A total of 15 staff surgeons and intensivists who collaborate in patient care in the surgical intensive care unit. RESULTS: The phenomenon of "resident bypass" emerged, resulting from staff surgeon and intensivist perceptions that residents threaten the quality of interspecialty team communication. Clear patterns and preferences for resident exclusion from this communication were present. A total of 5 interrelated drivers of resident bypass were discovered: lack of trust, lack of specialized knowledge, poor system design, need for timely communication, and residents' inadequate contribution to decision-making. Surgical and intensive care staff were dissatisfied with the structure of residents' roles in interspecialty team communication. Concerns about communication gaps, patient care continuity, and patient safety were expressed. CONCLUSIONS: Surgical and intensive care staff exclude residents from interspecialty team communication for the benefit of patient safety and care continuity, but this limits opportunities for residents to develop communication skill and competence. Efforts are needed to effectively integrate surgery and intensive care residents in interspecialty attending resident communication in ways that are meaningful for both patient care and postgraduate training. The implications for medical education are discussed. PMID- 26992942 TI - Calcium mobilisation following shell damage in the Pacific oyster, Crassostrea gigas. AB - Shell growth of oysters requires calcium uptake from the environment and transport to the area of shell formation. A shell regeneration assay in combination with radiolabelled calcium was used to investigate uptake and distribution of calcium to different tissues and hemolymph fractions in Pacific oysters, Crassostrea gigas (Bivalvia, Ostreoida). Oysters were notched at the shell margin and subsequently sampled for hemolymph and grading of shell regeneration during a two week experimental period. Half of the oysters were additionally exposed to (45)Ca and sampled for hemolymph and tissues. Total plasma calcium concentrations increased in notched oysters compared to controls on 1, 2 and 7days after notching. A decrease in plasma calcium levels was apparent on day 4, for both total and ionic calcium. The shell regeneration assay in the notched oysters resulted in a visible deposition of CaCO3 onto the regenerate from day 7 onwards. This was coinciding with an increased uptake of total calcium on days 11 and 14 as well as free, i.e. ionic and ligand-bound calcium, on day 14. At day 1, notching also increased calcium uptake into the mantle tissues, in areas above the notch and near the hinge. During the experiment, both the total hemocyte count and the number of granulocytes increased in notched compared to control oysters. The present study suggests that induced shell damage results in a dynamic regulation of the calcium uptake from the environment and the distribution of calcium within the body, starting directly after notching. Increases in both total calcium concentrations and uptake rates coincided with the visible depositions of CaCO3 on the regenerate shell. C. gigas was found to transport calcium mainly in the ionic form in the hemolymph, with only minor parts being bound to proteins or smaller ligands. Hemolymph measurement also revealed that C. gigas is able to regulate the extracellular concentrations of calcium and potassium. The changes in plasma calcium concentrations and speciation, concomitant with increases in granulocytes indicate that multiple calcium transport processes are activated after induced shell damage. PMID- 26992943 TI - Genetic analysis of five children with essential thrombocytosis identified mutations in cancer-associated genes with roles in transcriptional regulation. PMID- 26992944 TI - The efficacy of current prognostic models in predicting outcome of patients with myelodysplastic syndromes at the time of hypomethylating agent failure. PMID- 26992945 TI - APRIL levels are associated with disease activity in human chronic graft-versus host disease. PMID- 26992946 TI - Allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning regimen for elderly patients (60 years and older) with hematologic malignancies using unrelated donors: a retrospective study from the French society for stem cell transplantation (SFGM-TC). PMID- 26992947 TI - Immunohistochemical detection of inhibitor of DNA binding 3 mutational variants in mature aggressive B-cell lymphoma. PMID- 26992948 TI - Mutations of TP53 gene in adult acute lymphoblastic leukemia at diagnosis do not affect the achievement of hematologic response but correlate with early relapse and very poor survival. PMID- 26992949 TI - Systematic review: Health care transition practice service models. AB - BACKGROUND: Nearly 750,000 adolescents and emerging adults with special health care needs (AEA-SHCN) enter into adulthood annually. The linkages to ensure the seamless transfer of care from pediatric to adult care and transition to adulthood for AEA-SHCN have yet to be realized. PURPOSE: The purpose of this systematic review was to investigate the state of the science of health care transition (HCT) service models as described in quantitative investigations. METHODS: A four-tier screening approach was used to obtain reviewed articles published from 2004 to 2013. A total of 17 articles were included in this review. DISCUSSION: Transfer of care was the most prominent intervention feature. Overall, using the Effective Public Health Practice Project criteria, the studies were rated as weak. Limitations included lack of control groups, rigorous designs and methodology, and incomplete intervention descriptions. CONCLUSION: As the findings indicate, HCT is an emerging field of practice that is largely in the exploratory stage of model development. PMID- 26992950 TI - Ankylosing spondylitis: A cause of death after minor trauma. PMID- 26992951 TI - Management after first-line antiresorptive treatment for postmenopausal osteoporosis. PMID- 26992952 TI - Effects of bariatric surgery on bone. AB - Bariatric surgery currently relies on combinations of restrictive and malabsorptive procedures. Early decreases in bone mineral density (BMD) have been reported. However, the accuracy of dual-energy X-ray absorptiometry used to measure BMD can be diminished by the major weight loss, whereas quantitative computed tomography (QCT) measurements are less affected. The nutritional deficiencies induced by mixed bariatric surgery procedures, together with changes in hormones produced by adipocytes and/or the gastrointestinal tract, are often associated with elevations in serum levels of bone resorption markers. Although the data are limited, the incidence of fractures does not seem higher after bariatric surgery than in non-operated obese patients. PMID- 26992953 TI - Anti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthritis: Prevalence and associated phenotype. AB - OBJECTIVE: The aim of the study was to compare the prevalence of ASCA in spondyloarthrites (SpA) patients and to investigate the association between ASCA status and disease phenotype. METHODS: We performed a case-control study including SpA individuals fulfilling the ESSG SpA criteria. The following data were collected for analysis: gender, age, disease duration, clinical or associated features of SpA, treatments, HLAB27 and ASCA status. A control group of patients without SpA was also analyzed. RESULTS: A total of 235 patients with SpA and 54 control patients were studied. The median age of SpA patients (53.6% of male patients, 52.2% of HLAB27) was 46.0 [IQR 35.0-57.0] years old. Disease duration was 60.0 [IQR 24.0-156.0] months. Inflammatory bowel diseases were observed in 11% of SpA patients. ASCA positivity was significantly higher in SpA patients than in control patients (25.5% [95% CI 20.1-31.6] (IgG: 9.8%; IgA: 21.7%) vs. 7.4% [95% CI 2.1-17.9], P=0.004). Multivariate analysis revealed that ASCA positivity was associated with peripheral involvement (OR: 3.30 [1.26-8.62], P=0.015), presence of IBD (OR: 3.43 [1.15-10.20], P=0.026), past of present history of uveitis (OR: 4.36 [1.08-17.64], P=0.039) and arthritis (OR: 3.78 [1.57 9.15], P=0.003). CONCLUSION: Our results provided evidence that SpA patients had an increased prevalence of ASCA and that ASCA positivity might be associated with a particular phenotype, notably peripheral involvement and uveitis. PMID- 26992954 TI - Effect of age at rheumatoid arthritis onset on clinical, radiographic, and functional outcomes: The ESPOIR cohort. AB - OBJECTIVES: To investigate whether age at disease onset determines clinical, radiographic or functional outcomes in a cohort of early RA. METHODS: The ESPOIR cohort is a multicenter cohort of patients with early arthritis. We selected patients fulfilling the 2010 ACR/EULAR criteria for RA during the first 3years of follow-up. Patients were pooled into 3 groups by age at RA onset: <45years (young onset RA [YORA]), 45 to 60years (intermediate-onset RA [IORA]) and>60years (late onset RA [LORA]). The following outcomes were compared at baseline and during the first 3years of follow-up: Simple Disease Activity Index (SDAI) remission rate, one additional erosion, Health Assessment Questionnaire Disability Index (HAQ DI)<0.5 and first disease-modifying anti-rheumatic drug (DMARD) continuation rate. RESULTS: We included 698 patients (median [interquartile range] age 50.3 [39.8-57.2]years), 266 YORA, 314 IORA, and 118 LORA. At 1year, SDAI remission was greater for YORA than IORA and LORA (P<0.0001). Having at least one additional erosion was greater for LORA and IORA than YORA after 1year (P=0.009) and 3years (P=0.017). The proportion of patients with HAQ score<0.5 was greater for YORA than IORA and LORA at 1 (P=0.007), 2 and 3years. First DMARD continuation rate was lower for YORA than other groups during the 3years (P=0.005). CONCLUSIONS: In a cohort of early RA, young age at disease onset is associated with high rate of remission at 1year, no radiographic progression at 3years and low functional score during 3-year follow-up. PMID- 26992956 TI - Low back pain and femoral neuralgia revealing myeloid sarcoma with megakaryocytic differentiation. PMID- 26992955 TI - Atypical femoral fracture in a 51-year-old woman: Revealing a hypophosphatasia. AB - We report a 51-year old woman who suffered 2 atypical subtrochanteric femoral fractures (AFFs). She had a history of several metatarsal fractures. She had a normal bone densitometry. An adult form of hypophosphatasia (HPP) was diagnosed from low serum alkaline phosphatase (ALP), and tissue nonspecific isoenzyme of ALP (TNSALP) mutation analysis revealing 2 heterozygous mutations: c.299C>T (p. T100M) and c.571G>A (p. E191K). Low ALP is the hallmark of the diagnosis of HPP; which is associated in adults with premature loss of deciduous teeth, recurrent metatarsal stress fractures, and joints and tendons disorders. The incidence of AFFs in the population is 5.9 per 100,000 person-years. Physicians and patients with bone fragility must pay attention to prodromal pain, which require urgent radiographic evaluation of both femurs. Rheumatoid arthritis, use of glucocorticoids, and proton pump inhibitors have been associated with an excess risk of AFFs. Healthy subjects carrying a TNSALP mutation with low ALP value may be exposed to develop AFF spontaneously or while receiving potent anti-resorptive drugs. Low ALP must be checked as a cause of bone fragility. PMID- 26992957 TI - Exendin-4, a glucagon-like peptide 1 receptor agonist, protects against amyloid beta peptide-induced impairment of spatial learning and memory in rats. AB - Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share specific molecular mechanisms, and agents with proven efficacy in one may be useful against the other. The glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 has similar properties to GLP-1 and is currently in clinical use for T2DM treatment. Thus, this study was designed to characterize the effects of exendin-4 on the impairment of learning and memory induced by amyloid protein (Abeta) and its probable molecular underlying mechanisms. The results showed that (1) intracerebroventricular (i.c.v.) injection of Abeta1-42 resulted in a significant decline of spatial learning and memory of rats in water maze tests; (2) pretreatment with exendin-4 effectively and dose-dependently protected against the Abeta1-42-induced impairment of spatial learning and memory; (3) exendin-4 treatment significantly decreased the expression of Bax and cleaved caspase-3 and increased the expression of Bcl2 in Abeta1-42-induced Alzheimer's rats. The vision and swimming speed of the rats among all groups in the visible platform tests did not show any difference. These findings indicate that systemic pretreatment with exendin-4 can effectively prevent the behavioral impairment induced by neurotoxic Abeta1-42, and the underlying protective mechanism of exendin-4 may be involved in the Bcl2, Bax and caspase-3 pathways. Thus, the application of exendin-4 or the activation of its signaling pathways may be a promising strategy to ameliorate the degenerative processes observed in AD. PMID- 26992958 TI - Low calorie sweeteners and gut microbiota. AB - Studies dating back to 1980s, using bacterial cultures, have reported associations between low calorie sweeteners (LCS) and alterations in bacterial composition, raising the potential that LCS might exert effects on the host via interactions with gut microbiota. However, the results of a few recent studies carried out in this area have produced controversies. There is evidence that human fecal samples, used in most human microbiome studies, may provide a poor representation of microbial contents of the proximal intestine. Furthermore, fecal short chain fatty acid levels do not exemplify the amount of short chain fatty acids produced in the intestine. Short chain fatty acids are largely absorbed in the intestine by a tightly regulated mechanism. Here we present an exemplar study showing that the determination of the molecular mechanism(s) underlying the precise mode of action of a LCS on gut microbiota allows for rational and scientifically-based recommendations. PMID- 26992959 TI - Molecular mechanism of sweetness sensation. AB - The current understanding of peripheral molecular events involved in sweet taste sensation in humans is reviewed. Included are discussions of the sweetener receptor T1R2/T1R3, its agonists, antagonists, positive allosteric modulators, the transduction of its activation in taste bud cells and the coding of its signaling to the CNS. Areas of incomplete understanding include 1) signal communication with afferent nerve fibers, 2) contrasting concentration/response (C/R) functions for high-potency (HP) sweeteners (hyperbolic) and carbohydrate (CHO) sweeteners (linear), 3) contrasting temporal profiles for HP sweeteners (delayed onset and extinction) and CHO sweeteners (rapid onset and extinction) and 4) contrasting adaptation behaviors for HP sweeteners (moderate to strong adaptation) and CHO sweeteners (low adaptation). Evidence based on the sweet water aftertastes of several novel sweetness inhibitors is presented providing new support for constitutive activity in T1R2/T1R3. And a model is developed to rationalize the linear C/R functions of CHO sweeteners and hyperbolic C/R functions of HP sweeteners, where the former may activate T1R2/T1R3 by both binding and constitutive activity modulation (i.e., without binding) and the latter activate T1R2/T1R3 only by binding. PMID- 26992960 TI - Journal of Vascular Surgery: Venous and Lymphatic Disorders Editors' message. PMID- 26992961 TI - Endovascular treatment of iliofemoral chronic post-thrombotic venous flow obstruction. AB - INTRODUCTION: Patients with deep vein thrombosis affecting the iliac and vena cava veins develop a more severe post-thrombotic syndrome than those with femoropopliteal disease. It has been traditionally treated only with medical therapy. During the last decade, endovascular repair has become the treatment of choice. The aim of this study is to report our midterm results using this technique. METHODS: From 2009 to 2012, 41 limbs in 36 patients with post thrombotic chronic flow obstruction of iliofemoral vein secondary to stenotic or occlusive lesions and with a clinical CEAP class 3 or higher or venous pain underwent percutaneous treatment. Stent-related outcome (patency and thrombotic events), clinical outcome (improvement of revised Venous Clinical Severity Score [VCSS] and Villalta score) were evaluated after intervention. RESULTS: The procedure was successful in 39 limbs (95%) with no mortality and low morbidity. Thrombotic events occurred in nine limbs (23%) during the follow-up period. At 33 months, primary, assisted-primary, and secondary cumulative patency rates were 74%, 87%, and 89%, respectively. The main risk factor associated with stent occlusion was the severity of thrombotic disease. All postoperative thrombotic events occurred in occluded veins; no previously stenotic veins presented any complication (P = .04). Presence of thrombophilia, stent brand, and stent extension into the common femoral vein were not significantly associated with stent thrombosis. After surgery, the mean revised VCSS and Villalta scores improved substantially (P < .0001). The cumulative rate of revised VCSS improvement was 89% at 33 months. Clinical improvement was observed despite deep venous system reflux remaining uncorrected. CONCLUSIONS: Percutaneous treatment of post-thrombotic venous flow obstruction is an excellent therapeutic option with low morbidity and no mortality. It can be performed with high midterm patency rates and midterm clinical improvement. PMID- 26992962 TI - Validation of the Villalta scale in assessing post-thrombotic syndrome using clinical, duplex, and hemodynamic comparators. AB - INTRODUCTION: The Villalta scale (VS) was developed by Prandoni and introduced as an abstract in 1994 as a disease-specific assessment questionnaire to diagnose and classify the severity of post-thrombotic syndrome (PTS). While validation using quality-of-life assessments and reproducibility have been reported as good, limited data exist as how the VS compares against generalized assessment tests in defining the severity of PTS. The aim of this study was to compare the VS against the Venous Clinical Severity Score (VCSS), the C of the CEAP classification, the Venous Segmental Disease Score (VSDS), and the Venous Filling Index (VFI) of air plethysmography. METHODS: Baseline data generated from a recent single-center prospective clinical trial comparing graduated elastic compression stocking performance on 40 legs in 34 patients with PTS were analyzed. Ancillary data from this study were used to assess the measurement properties of the VS. All the legs had PTS defined as persisting leg symptoms/signs at least 6 months after a deep vein thrombosis with evidence of deep venous obstruction and/or deep venous reflux on duplex ultrasound. Unadjusted VS scores were used so patients with ulceration with a VS <15 were not automatically upgraded to a score of 15. RESULTS: The number of legs by the C part of the CEAP classification was: C0 = 2, C2 = 1, C3 = 3, C4a = 12, C4b = 7, C5 = 12, and C6 = 3. The median (interquartile range) of age, VS, VCSS, VSDS, and VFI were 62 years (52-73 years), 10 (5-14), 8 (5-10), 5 (4-6.5), and 4.9 (2.8-7.9) mL/s, respectively. The VS had a highly significant and moderate-to-good correlation (Spearman) with the VCSS (r = .609; P < .0005) and the C of CEAP (r = .556, P < .0005). When the VFI was used as a hemodynamic benchmark, the VS correlation outperformed the other assessment tests (r = .499; P = .001). However, the VCSS correlation with the VFI was also significant (r = .480; P = .002). Surprisingly, the VSDS did not correlate with any assessment tests. No correlation could be detected within the VS between patient symptoms and their clinical signs. Correlations between the VS and the VCSS (r = .775) and C class (r = .779) improved when the VS patient-reported part was excluded. CONCLUSIONS: These results indicate that the VCSS and the C of CEAP may also be useful in the assessment of PTS severity, and the VFI may provide a clinically meaningful hemodynamic evaluation. However, using the VFI as a reference, there was no essential difference between the VS and the VCSS. PMID- 26992963 TI - National trends in utilization of inferior vena cava filters in the United States, 2000-2009. AB - OBJECTIVE: To characterize national trends over a decade in utilization of inferior vena cava (IVC) filters in the U.S. by year, indication, hospital, and patient demographics. METHODS: Retrospective cross-sectional study utilizing the Nationwide Inpatient Sample Database, 2000 to 2009. IVC filter placement was identified with International Classification of Disease, Ninth Edition codes. Survey weighting, bivariate, and multivariate analysis was performed. RESULTS: The number of IVC filters placed in the U.S. increased by 234% over a decade, from 56,380 in 2000 to 132,049 in 2009. A total of 84.7% of patients had a pulmonary embolism or deep venous thrombosis. A total of 94.6% of IVC filters were placed in urban hospitals. The largest number of IVC filters was placed in the South, followed by the Northeast, Midwest, and Western regions (38.7%, 25.8%, 22.4%, and 13%, respectively). Adjusting for other patient and hospital factors, independent predictors of IVC filter placement were year, hospital size, location, teaching status, patient age group 50 to 79 years, insurance status, and urgency of admission. CONCLUSIONS: The use of IVC filters has dramatically increased over the last decade in the U.S., with variation in utilization based on patient and hospital characteristics. The largest utilization of IVC filters was among patients aged 50 to 79 years, Medicare recipients, and the Southern region of the U.S. The majority of patients receiving IVC filters have a diagnosis of pulmonary embolism or deep venous thrombosis. PMID- 26992964 TI - Factors affecting Cook Gunther Tulip and Cook Celect inferior vena cava filter retrieval success. AB - OBJECTIVE: Success rates vary for the retrieval of inferior vena cava filters (IVCFs). The optimal retrieval time and factors influencing retrieval success remain unproven. This study aims to determine optimal time and evaluate factors related to successful IVCF retrieval. METHODS: An institutional prospectively maintained database was reviewed for all IVCF retrieval attempts from 2006 to 2012. Patient demographics, comorbidities, indications for procedure, placement technique, IVCF type, presence of angulation, and time to retrieval were evaluated with respect to success or failure of retrieval. Statistical analyses (t-test, chi(2), correlations, and Kaplan-Meier plots) were performed comparing successful and unsuccessful retrievals. RESULTS: Of 121 attempted IVCF retrievals, 92 (76%) were successful and 29 (24%) were unsuccessful. There were no significant differences between the successful and unsuccessful attempts in terms of patient demographics, comorbidities, indications for procedure, placement technique, or IVCF type, which included 93 Celect (77%) and 28 Gunther Tulip (23%). Time since IVCF placement was significantly different (P = .025) between the successful and unsuccessful retrieval groups (medians were 105 [7 368] and 162 [43-379] days, respectively). Time since IVCF placement greater than 117 days correlated significantly with unsuccessful IVCF retrieval (R = 0.218; P = .017; odds ratio, 2.88; P = .02). Angulation greater than 20 degrees on anteroposterior radiograph was noted in seven of 29 (24%) unsuccessful retrievals compared with seven of 92 (8%) successful retrievals and was significant (P = .012). CONCLUSIONS: Cook Gunther Tulip and Celect IVCF retrieval is most likely to be successful within 3 to 4 months of placement. Unsuccessful retrieval attempts are more likely to occur when IVCF position is angulated. PMID- 26992965 TI - Hemodynamic changes in the femoral vein with increasing outflow resistance. AB - INTRODUCTION: In post-thrombotic and May-Thurner syndromes, the iliac veins may be scarred, compressed, or obstructed. Obesity and increased intra-abdominal pressure may also hamper the venous return. Therefore, measurements of outflow resistance (OR) impeding venous return may be helpful to select patients for intervention and to assess the impact of intervention. A proof-of-concept study is presented in healthy volunteers where OR is quantified using duplex assessment of the femoral vein (FV) at mid-thigh following predetermined inflation pressures with a high thigh tourniquet. METHODS: Twenty-two consecutive subjects (15 male) without evidence of venous disease by clinical and duplex examination were studied. Two male exclusions were due to bifid FVs. Median (range) baseline characteristics were age 30 years (24-57 years), height 173 cm (158-197 cm), weight 72 kg (50-97 kg), leg length 80 cm (74-94 cm), and FV diameter 11.2 mm (6.8-14.8 mm). Subjects were examined standing with the test leg nonweight bearing, resting gently on the floor. A 26-cm-wide calf cuff was attached to an intermittent pneumatic compression device that delivered three compressions per minute at 120 mm Hg. A high thigh cuff, 12 cm wide, was inflated just before each calf compression in multiples of 20 mm Hg, from 0 to 120 mm Hg, to provide a standard OR. FV waveform parameters were recorded using duplex beneath each thigh cuff inflation pressure and repeated three times. OR was calculated using change in pressure (P2-P1)/Flow (Q). Pressure P2 was 120 mm Hg minus the additional height to the duplex transducer. P1 was assumed to be zero. Flow was cross sectional area (pi * diameter [d](2)/4) * velocity. The velocity parameters chosen were peak velocity (PV), time-averaged mean velocity (TAMV), and TAMV from start to peak. RESULTS: Peak velocity, TAMV, and TAMV to peak all decreased significantly (P < .0005; Friedman) with increasing thigh cuff pressure with P < .0005 correlations (Spearman) of r = .842, r = .488, and r = .744, respectively. Furthermore, increasing thigh cuff pressure at 0, 20, 40, 60, 80, 100, and 120 mm Hg also caused a gradual and significant increase in median (interquartile range) OR at 27 (19-34), 30 (21-42), 30 (23-44), 40 (26-47), 46 (32-51), 61 (38-71), and 79 (45-134) resistance units, respectively (P < .0005; Friedman, and r = .516; Spearman). Higher baseline (innate) OR values were found in taller (P = .002) and heavier (P = .043) subjects. CONCLUSIONS: Hemodynamic velocity parameters in the femoral vein attenuate progressively with increasing venous obstruction. Outflow resistance (OR) can be quantified using duplex measurements when they are substituted into equations of fluid mechanics. Optimization of this novel technique, which requires an IPC outflow challenge test, may provide useful information in the assessment and treatment of patients. PMID- 26992966 TI - The role of duplex ultrasound in the workup of pelvic congestion syndrome. AB - BACKGROUND: Pelvic congestion syndrome (PCS) imaging workup algorithms are not well-defined. The purpose of our study is to gauge the impact and accuracy of duplex ultrasound (DU) to assist in the diagnosis of PCS. METHODS: We reviewed the records of 48 patients with PCS seen at a vein center from June 2010 to June 2012. All patients had DU plus either computed tomography venography (CTV) or conventional venography (CV). Measurements of the left (LOV) and right ovarian vein (ROV) diameter and the presence or absence of ovarian vein reflux were obtained using DU and compared with either CTV or CV to assess sensitivity and specificity. An ovarian vein diameter >6 mm was considered abnormal. RESULTS: All patients were female (29 Caucasians, 18 Hispanic, and 1 Asian). The mean number of pregnancies was 3 (range, 1-5). All patients had lower extremity varicose veins, and 14 (29%) had vulvar varicosities. Thirty-four (71%) patients reported pelvic pain, 22 (46%) dyspareunia, 2 (4%) dysuria, and 1 (2%) hematuria. The median diameter of the LOVs and ROVs measured using DU compared with either CTV/CV were similar (DU, 8.6 and 5.6; CTV/CV, 8.3 and 6). The sensitivity and specificity of DU to demonstrate a dilated LOV were 100% and 57%, and for the ROV were 67% and 90%. Pelvic varicosities were identified in all but one patient with good correlation between DU and CV. CONCLUSIONS: DU has a high sensitivity to identify an abnormal LOV diameter that is greatly reduced when evaluating the ROV; however, the latter can be evaluated with another imaging modality such as CTV especially when DU results are equivocal or negative. A moderate specificity was found to determine both LOV and ROV abnormal diameters. All three imaging modalities are equally accurate to show the presence of pelvic varices. PMID- 26992967 TI - Validation of lower limb segmental volumetry with hand-held, self-positioning three-dimensional laser scanner against water displacement. AB - BACKGROUND: Measurement of limb volume is helpful for the evaluation and follow up of edema, especially in patients with chronic venous insufficiency (CVI) or lymphedema. Water displacement (WD) is the reference method for limb volumetry but is not really suitable for clinical routine. Indirect volumetry based on circumference measurements as well as the more expansive but automatic optoelectronic techniques do not allow detailed measurement at the extremity of the limb. METHODS: We used a self-positioning laser scanner with dynamic referencing for acquisition and real-time three-dimensional (3D) reconstruction of the lower limb volume in 30 patients with CVI, 30 patients with lymphedema, and 30 healthy controls. Two independent observers performed either one or two laser scans, whose results were tested for intra- and interobserver reproducibility and compared with WD volumetry by Lin's concordance correlation coefficient and Bland and Altman graphic analysis. RESULTS: Automatic volume calculation from 3D laser scanning data failed in one patient with major lymphedema. Lin's concordance correlation coefficient was 0.99 and 0.98, respectively, for intraobserver no. 1 and no. 2, 0.98 for interobserver reproducibility, and 0.98 and 0.96, respectively, for observer no. 1 and observer no. 2 vs WD comparison. The 3D laser scanning yielded 1.99% precision. Accuracy was 3.12% for observer no. 1 and 2.71% for observer no. 2, laser scanning values being 90 mL higher than WD, which could be attributed to the different posture during measurement. CONCLUSIONS: Three-dimensional laser scanning is accurate and reproducible, and appears suitable for the evaluation of limb volume in patients with CVI or lymphedema. PMID- 26992968 TI - Quality of life in patients with congenital vascular malformations. AB - OBJECTIVE: To assess quality of life (QoL) in patients with congenital vascular malformations (CVMs) and to identify factors of CVMs associated with poor QoL, including high psychological and/or somatic (physical) distress. METHODS: We evaluated 71 patients (mean age, 40 +/- 16 years; 51% women) with arteriovenous (n = 10), venous/capillary (n = 34), lymphatic (n = 10), and combined (n = 17) malformations. All patients completed validated psychometric assessment tools, which were the 36-Item Short Form Health Survey, the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-15, and the Pain Disability Index. RESULTS: Compared with population norms, the group of CVM patients as a whole showed lower 36-Item Short Form Health Survey Physical (46 vs 50) and Mental (46 vs 52) Component Summary scores, indicating impaired physical and mental health. In addition, 13% of patients with CVMs had clinically relevant psychological distress (Hospital Anxiety and Depression Scale total scores >=17), and 15% had increased somatic distress (Patient Health Questionnaire-15 total scores >=10). Greater levels of psychological and somatic distress were significantly associated with lower scores of virtually all of the eight 36-Item Short Form Health Survey subscales (P < .05). CONCLUSIONS: Our findings suggest that, compared with a normal population, CVM patients have a lower QoL that is accompanied by increased psychological and somatic distress. In treating patients with CVMs, it is important to be aware of the psychological impact of this rare illness and to offer appropriate support. PMID- 26992969 TI - Hemodynamics of "critical" venous stenosis and stent treatment. AB - BACKGROUND: The concept of "critical" stenosis at which there is a sharp reduction in forward flow is derived from arterial disease. The critical element in venous stenoses is upstream pressure, not downstream flow. Many venous symptoms and microvascular injury are related to venous hypertension. We studied the effect of venous stenosis on upstream pressure using a mechanical model and with clinical measurements after stenting of iliac vein segments (common and external). METHODS: The experimental model consisted of a Starling Resistor - Penrose tubing enclosed in a pressurized plastic chamber to simulate abdominal venous flow. Clinical measurements included time-averaged velocity, area, rate of flow, and quantified phasic flow volume in the common femoral vein before and after iliac vein stenting. Traditional air plethysmography and occlusion plethysmography were also performed. RESULTS: The mechanical model showed that upstream pressure varied based on (1) volume of venous inflow, (2) abdominal pressure, (3) outflow pressure, and (4) outflow stenosis. Upstream pressure changes were inverse to flow as kinetic energy was converted to pressure as required. A venous stenosis of as little as 10% raised upstream pressure in the model when the abdominal pressure was low, but high grades of stenosis had no contribution when abdominal pressure was high. Stenting of the Penrose moderated or nullified upstream pressure changes related to abdominal pressure. There was significant decompression of the common femoral vein, implying pressure reduction after stenting; median area reduction was 15% and 10% in erect and supine, respectively. Air plethysmography showed improvement in venous volume and in other parameters in confirmation of venous decompression. There was significant prolongation of phasic flow duration and quantitative phasic flow increased (median, 16%) after stenting in the erect position. There was no increase in arterial inflow. CONCLUSIONS: The criticality of iliac vein stenosis is based on peripheral venous hypertension, which is controlled by more confounding factors than in arterial stenosis. The experimental model clarifies the interplay of the many variables. Clinical measurements indicate that iliac vein stenting results in decompression of the limb veins and, by inference, a reduction in venous pressure. Venous flow is improved less consistently and, in part, is related to an increase in duration of phasic flow. Limb arterial flow is not increased, and the venous flow changes are likely the result of rearrangement of the velocity and pressure components of venous flow. PMID- 26992970 TI - Invited Commentary. PMID- 26992971 TI - Influence of fibers and wavelengths on the mechanism of action of endovenous laser ablation. AB - OBJECTIVE: This study aimed to investigate the different mechanisms involved in the use of bare, radial, and two-ring fibers, operating at 980- or 1470-nm wavelengths, by analyzing the histological changes caused to irradiated human great saphenous veins (GSVs). METHODS: GSVs were removed by invaginated stripping and were prepared for irradiation. Irradiation was performed using bare, radial, and two-ring fibers, combined with 980- and 1470-nm laser wavelengths, operating at powers of 6 to 12 W. The fibers moved through the GSVs at a speed of 1 mm/s. The circumferences of the irradiated veins were measured, and the histological changes were examined. RESULTS: The use of the bare fibers resulted in an average shrinkage ratio that increased with increasing laser power, regardless of the wavelength. Microscopic changes were heterogeneous and included carbonization and ulceration at the side where the heated fiber tip contacted the vessel wall, and sparse low-temperature changes were evident more distant from the fiber, regardless of the wavelength of the laser used. Using radial or two-ring fibers, the thermal changes were circumferentially uniform, but the shrinkage ratio and microscopic changes varied according to the laser wavelength combined. With the 1470-nm laser, the average shrinkage ratio did not vary significantly between different outputs. Mid-temperature changes were spread across the intima and superficial layer of the media, without causing carbonization. With the 980-nm laser, the average shrinkage ratio increased depending on the output. Conducted heat caused carbonization of the superficial part of the intima, with a thin layer of additional mid-temperature changes. Although adhesion of the hot fiber to the vessel wall was an annoying phenomenon during endovenous laser ablation and occurred frequently in the radial-1470 experiments, it rarely occurred in the two-ring-1470 experiments. CONCLUSIONS: Using bare fibers, direct contact between the unevenly placed heated tip and the vessel wall results in heterogeneous heating of the vein. Radial and two-ring fibers, combined with 1470-nm light, can heat vessel walls circumferentially and uniformly with the laser light emitted radially penetrating into the vessel wall. Regarding the longitudinal uniformity, two-ring fibers provide a greater uniformity with a reduced incidence of sticking. PMID- 26992972 TI - Chest pain from excluded inferior vena cava filter after stent placement. AB - A 52-year-old patient presented with chronic substernal chest pain 18 months following exclusion of an inferior vena cava (IVC) filter with a self-expanding IVC stent. After a thorough work-up revealed no other possible cause of chest pain, the filter and stent were removed with subsequent resolution of chest pain. Intraoperatively, filter struts were found to have penetrated the posteromedial wall of the IVC and were abutting the periaortic neural plexus. Referred chest pain due to strut penetration of the caval wall is a novel complication of both IVC filters and IVC stents, demonstrating a need for continued surveillance. PMID- 26992973 TI - Delayed reconstruction with cryopreserved vein of an iatrogenically ligated inferior vena cava. AB - We report the case of delayed reconstruction of an iatrogenically transected inferior vena cava (IVC). A 47-year-old male underwent a laparoscopic right nephrectomy complicated by an unrecognized IVC transection. Postoperatively, he developed severe lower extremity edema, abdominal distension, and discomfort, prompting further investigation. A computed tomography scan showed a staple line extending across the IVC with thrombus extending distally to the level of the left renal vein. Repair of the suprarenal portion of the IVC was undertaken using a cryopreserved femoral vein allograft. The patient demonstrated clinical improvement with follow-up imaging demonstrating graft patency at 15 months. PMID- 26992974 TI - Thyrocervical trunk and external jugular vein arteriovenous fistulas. PMID- 26992975 TI - Biomarkers for post-thrombotic syndrome. AB - BACKGROUND: Post-thrombotic syndrome (PTS) is a serious condition that occurs in 20%-50% of patients following deep venous thrombosis (DVT). Biomarkers can be of use in further exploring the etiology as well as in developing risk stratification tools for PTS. The relationship between PTS and specific biomarkers may help guide prevention and therapy based on a patient's individual risk profile. This review gives an overview of the current knowledge on biomarkers in relation to PTS. METHODS: A systematic search was executed in three databases (Pubmed, Embase/Medline, Cochrane) to identify all publications on biomarkers in relation to PTS. Where possible, results of studies were pooled and a meta-analysis was performed using Review Manager 5.1 (The Cochrane Collaboration). RESULTS: Twenty-four papers were included in this review. In patients after DVT, increased D-dimer appeared to be associated with the development of PTS (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.02 4.08; P = .04). Neither prothrombin G20210A (OR, 0.95; 95% CI, 0.53-1.69; P = .86, nor increased factor VIII (OR, 1.78; 95% CI, 0.88-3.57; P = .11) were associated with PTS. For factor V Leiden (FVL), conflicting results were found. FVL was not associated with PTS within a population of patients with a history of DVT (OR, 0.98; 95% CI, 0.74-1.29; P = .88), but FVL was positively associated with post-thrombotic ulceration in severe PTS, in patients compared with healthy individuals without a history of DVT (OR, 11.42; 95% CI, 6.37-20.48; P < .00001). A meta-analysis could not be performed for markers of inflammation and tissue remodelling in relation to PTS. CONCLUSIONS: Increased D-dimer levels are associated with a twofold increased risk for PTS. Inherited hypercoagulability, including FVL is not associated with PTS in general. In contrast, FVL is strongly associated with post-thrombotic ulceration in severe PTS. The role of inflammation in the etiology of PTS still has to be elucidated. PMID- 26992976 TI - In with the old, out with the new: The American Venous Forum leads the way. PMID- 26992978 TI - Discussion. PMID- 26992977 TI - A novel technique to remove inferior vena cava filters using a homemade snare device. AB - The need to retrieve inferior vena cava filters is quite evident due to the long term complications. We present a novel technique to remove inferior vena cava filters using a homemade snare created using a looped a 0.014-inch semistiff wire. Employing this technique, 18 consecutive retrievable filters were removed. All filters were easily snared on the very first attempt, and no complications occurred. Our novel technique to retrieve filters is efficient, safe, and cost effective. PMID- 26992980 TI - Five-Year Results of a Randomised Clinical Trial Comparing Concomitant and Sequential Phlebectomy Following Endovenous Laser Ablation. PMID- 26992979 TI - Cost analysis of endovenous catheter ablation versus surgical stripping for treatment of superficial venous insufficiency and varicose vein disease. AB - BACKGROUND: Due to its clinical efficacy and faster recovery, endovenous catheter ablation has become the treatment of choice over surgical intervention for patients with varicose veins secondary to saphenous vein reflux. METHODS: A retrospective analysis of costs was performed on patients undergoing vein stripping, endovenous radiofrequency ablation (RFA), endovenous laser treatment (EVLT), and phlebectomy of varicosities at a community hospital and a tertiary care hospital in southeastern Michigan. RESULTS: In 2010 to 2011, higher costs resulted in a net loss per case for vein stripping, RFA, and phlebectomy procedures performed in the operating room for the community hospital. In contrast, RFA, EVLT, and phlebectomy procedures performed in an office setting resulted in a net profit for the tertiary care institution. CONCLUSIONS: Treatment of saphenous vein reflux and varicose vein disease with vein stripping was associated with higher costs than RFA and EVLT. Endovenous RFA performed in the operating room is associated with net loss per case vs office-based interventions. At present, catheter-based interventions in an office setting can be considered the more cost-effective method for treating patients with superficial venous reflux and varicose veins. PMID- 26992981 TI - An Integrated Subgroup Analysis of the Effect of Treatment with Polidocanol Endovenous Microfoam on VVSymQ Score in Patients with Varicose Veins. PMID- 26992982 TI - Clinical Presentation of Women with Pelvic Source Varicose Veins in the Perineum: First Steps in the Development of a Disease-Specific Patient Assessment Tool. PMID- 26992983 TI - Significance of Patent Saphenous Vein Stump Length After Endothermal Ablation. PMID- 26992984 TI - Predictive Value of a Preoperative Test for the Reversibility of the Reflux After Phlebectomy with Preservation of the Great Saphenous Vein. PMID- 26992985 TI - Twelve-Month Follow-up of the European Multicenter Study on Cyanoacrylate Embolization of Incompetent Great Saphenous Veins. PMID- 26992986 TI - Initial In-Vivo Evaluation of Safety and Performance of Nitinol Venous Stent in a Large Ovine Animal Iliac Venous Model. PMID- 26992987 TI - Assessment of Postoperative and Postintervention Remodeling with Dynamic CT Venography After Treatment of Chronic Venous Obstructions: Important Observations. PMID- 26992988 TI - Relative Importance of Iliac Vein Obstruction in Patients with Post-Thrombotic Femoral Vein Occlusion. PMID- 26992989 TI - Nanoparticle-Mediated Gene Delivery via Balloon Angioplasty to Suppress Intimal Hyperplasia. PMID- 26992990 TI - Treatment of IVC Thrombosis in Patients Undergoing Iliocaval Stenting for Acute or Chronic Venous Obstruction. PMID- 26992991 TI - Long-Term Outcomes and Predictors of Failure of Thrombolysis for Iliofemoral Deep Venous Thrombosis. PMID- 26992992 TI - Axitinib Treatment Impairs Venous Thrombus Resolution. PMID- 26992993 TI - Deep Vein Thrombosis: Final Report of the Prospective Multicenter Pearl Registry on Endovascular Treatment. PMID- 26992994 TI - Enough of EMR-Based VTE Risk Scores: We Need to Implement VTE Prophylaxis Based on These Alerts. PMID- 26992995 TI - Identification and Treatment of Restenosis in Failing Venous Stents: The Role of Intravascular Ultrasound. PMID- 26992996 TI - The Natural History and Treatment Outcomes of Symptomatic Ovarian Vein Thrombosis. PMID- 26992997 TI - Utility of Iliac Vein Stenting in Elderly Population Over Age Eighty. PMID- 26992998 TI - Measurements of Calf Muscle Oxygenation During Standing and Exercise in the Long Term Follow-up of the First Episode of Proximal Deep Vein Thrombosis. PMID- 26992999 TI - Human Chronic Post-Thrombotic Intraluminal Venous Obstruction Involves Neovascularization. PMID- 26993000 TI - A New Tool to Study the 3D Venous Anatomy of the Human Embryo: The Computer Assisted Anatomical Dissection. PMID- 26993001 TI - Thigh Compression Significantly Improves Venous Emptying After Deep Vein Thrombosis. PMID- 26993002 TI - Results of the TAHOE I and II Studies: Use of a Novel Biodegradeable Implant to Treat Refluxing Great Saphenous Veins. PMID- 26993003 TI - The Durability of Polidocanol Endovenous Microfoam Treatment Effect on Varicose Vein Symptoms and Appearance in Patients with Saphenofemoral Junction Incompetence: One-Year Results from the VANISH-2 Study. PMID- 26993004 TI - Defining Great Saphenous Vein Closure Rates for Ultrasound-Guided Foam Sclerotherapy. PMID- 26993005 TI - Midterm Results of a Randomized Controlled Trial Comparing Endovenous Laser Ablation and Surgery for the Treatment of Small Saphenous Insufficiency. PMID- 26993006 TI - Differential Metabolic Phenotype of Human Varicose Veins Tissue and Their Utility in Understanding Disease Pathogenesis and Identifying Potential Prognostic Biomarkers. PMID- 26993007 TI - Morphological Changes in the Vein After Different Numbers of Radiofrequency Ablation Cycles. PMID- 26993008 TI - P-Selectin Inhibition Therapeutically Promotes Thrombus Resolution and Prevents Vein Wall Fibrosis Better than Enoxaparin and an Inhibitor to von Willebrand Factor. PMID- 26993009 TI - Regional and Systemic Prothrombotic Biomarkers in Varicose Vein Patients and Healthy Controls. PMID- 26993010 TI - Saphenous Vein Radiofrequency Ablation Employing Enhanced Leg Elevation. PMID- 26993011 TI - Venous Reflux Duplex Ultrasound Objective Structured Assessment of Technical Skills (V-DUOSATS). PMID- 26993012 TI - Twelve-Month Experience Using Reprocessed ClosureFast Radiofrequency Catheters. PMID- 26993013 TI - The Effects of Altitude, Temperature, Gas to Sclerosant Ratio, Air Versus 50:50 Mixture of CO2 and O2, Foam Volume, Presence of Silicone, and Consecutive Uses of Syringes on the Longevity of Tessari-Made Foam for Sclerotherapy. PMID- 26993014 TI - Treatment of Nutcracker Syndrome with Open and Endovascular Interventions. PMID- 26993015 TI - Clinical Correlation of Anatomical Location of Nonthrombotic Iliac Vein Lesion. PMID- 26993016 TI - Short-Term Clinical Experience with a Dedicated Venous Stent. PMID- 26993017 TI - Rheolytic-Accelerated Pharmacomechanical Directional "RAPID" Thrombectomy Technique: A Method for Rapid Clot Removal with Reduced Need for Catheter Directed Thrombolysis in Patients with Acute DVT. PMID- 26993019 TI - Role of Coexisting Primary Chronic Venous Disease in Development of Post thrombotic Syndrome following Catheter-Based Treatment of Iliofemoral DVT. PMID- 26993018 TI - Hemodynamic Role of Sinus on Venous Valve Performance. PMID- 26993020 TI - Tracking Breeds Success: Improved Retrieval Rates of Inferior Vena Cava Filters with Minimal Dedication of Resources. PMID- 26993021 TI - Metabolic Profiling in Chronic Venous Ulceration of the Lower Limb: A New Approach to an Old Problem? PMID- 26993022 TI - Transvascular Autonomic Modulation: Novel Venous Therapy for Autonomic Dysfunction. PMID- 26993023 TI - Placement of Inferior Vena Cava Filters in a Real-World Setting Using the American Venous Forum Filter Registry. PMID- 26993024 TI - Readability and Availability of Online Treatment Options for Varicose Vein Patients. PMID- 26993025 TI - Characterization of a Bioprosthetic Bicuspid Venous Valve Hemodynamics and Implications for Mechanism of Valve Dynamics. PMID- 26993026 TI - Regarding "Multicenter assessment of the repeatability and reproducibility of the revised Venous Clinical Severity Score (rVCSS)". PMID- 26993027 TI - Reply. PMID- 26993028 TI - Zika virus - an overview. AB - Zika virus (ZIKV) is currently one of the most important emerging viruses in the world. Recently, it has caused outbreaks and epidemics, and has been associated with severe clinical manifestations and congenital malformations. However to date, little is known about the pathogenicity of the virus and the consequences of ZIKV infection. In this paper, we provide an overview of the current knowledge on ZIKV. PMID- 26993030 TI - Trypanosome-induced Interferon-gamma production in whole blood stimulation assays is associated with latent Trypanosoma brucei gambiense infections. AB - Control of human African trypanosomiasis (HAT) is highly dependent on the ability to detect and treat infected individuals. However, a number of individuals exposed to Trypanosoma brucei gambiense are able to control infection to undetectable levels in blood. They are long-term potential reservoirs and thus a threat for control strategies. Cytokine responses in whole blood stimulation assays were quantified in individuals with contrasting HAT status. Trypanosome induced IFN-gamma production was only observed in "trypanotolerant" subjects suspected of harboring latent infections. This result contributes new insights into the immune responses associated with infection control and opens novel diagnosis perspectives regarding HAT elimination. PMID- 26993031 TI - Pedunculated Papule and Fissure in the Anterior Midline of the Neck. PMID- 26993029 TI - Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease. AB - Lyme disease (LD) is a systemic disorder caused by Borrelia burgdorferi. Lyme spirochetes encode for a functional 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR EC 1.1.1.88) serving as a rate limiting enzyme of the mevalonate pathway that contribute to components critical for cell wall biogenesis. Statins have been shown to inhibit B. burgdorferi in vitro. Using a mouse model of Lyme disease, we found that statins contribute to reducing bacterial burden and altering the murine immune response to favor clearance of spirochetes. PMID- 26993032 TI - Cervical Cancer and Human Papilloma Virus. PMID- 26993033 TI - Cervical Cancer: The Next Generation of Prevention, Detection, and Treatment. PMID- 26993034 TI - Panimmunoglobulin and IgE-selective extracorporeal immunoadsorption in patients with severe atopic dermatitis. PMID- 26993035 TI - Counterregulation between thymic stromal lymphopoietin- and IL-23-driven immune axes shapes skin inflammation in mice with epidermal barrier defects. AB - BACKGROUND: Epidermal barrier dysfunction has been recognized as a critical factor in the initiation and exacerbation of skin inflammation, particularly in patients with atopic dermatitis (AD) and AD-like congenital disorders, including peeling skin syndrome type B. However, inflammatory responses developed in barrier-defective skin, as well as the underlying mechanisms, remained incompletely understood. OBJECTIVE: We aimed to decipher inflammatory axes and the cytokine network in mouse skin on breakdown of epidermal stratum corneum barrier. METHODS: We generated Cdsn(iep-/-) mice with corneodesmosin ablation in keratinocytes selectively in an inducible manner. We characterized inflammatory responses and cytokine expression by using histology, immunohistochemistry, ELISA, and quantitative PCR. We combined mouse genetic tools, antibody-mediated neutralization, signal-blocking reagents, and topical antibiotic treatment to explore the inflammatory axes. RESULTS: We show that on breakdown of the epidermal stratum corneum barrier, type 2 and type 17 inflammatory responses are developed simultaneously, driven by thymic stromal lymphopoietin (TSLP) and IL 23, respectively. Importantly, we reveal a counterregulation between these 2 inflammatory axes. Furthermore, we show that protease-activated receptor 2 signaling is involved in mediating the TSLP/type 2 axis, whereas skin bacteria are engaged in induction of the IL-23/type 17 axis. Moreover, we find that IL 1beta is induced in skin of Cdsn(iep-/-) mice and that blockade of IL-1 signaling suppresses both TSLP and IL-23 expression and ameliorates skin inflammation. CONCLUSION: The inflammatory phenotype in barrier-defective skin is shaped by counterregulation between the TSLP/type 2 and IL-23/type 17 axes. Targeting IL-1 signaling could be a promising therapeutic option for controlling skin inflammation in patients with peeling skin syndrome type B and other diseases related to epidermal barrier dysfunction, including AD. PMID- 26993036 TI - Increased expression of nuclear factor of activated T cells 1 drives IL-9 mediated allergic asthma. PMID- 26993038 TI - Child Witnesses to Intimate Partner Violence: Their Descriptions of Talking to People About the Violence. AB - Witnessing intimate partner violence (IPV) may have damaging effects on children's well-being and development. How children understand IPV affects the risk of their developing negative outcomes. Talking with children about the violent episodes they have experienced can change their beliefs regarding their parents' IPV, and therefore may also be a way to help them deal with these adverse experiences. The purpose of the current study was to use the children's narratives to explore the relationship between how IPV was perceived by the children and their experience of talking about it. Interviews with 31 children between 9 and 13 years of age were analyzed using a thematic method. Two main groups of children were identified: children who described the violence as a horrifying experience and children who preferred not to think about the violence. The findings showed that children who described the violence as a horrifying experience perceived talking about the violence as a positive, yet sometimes distressing, experience that made a real difference in their lives; whereas, children who preferred not to think about the violence did not see much need to talk about it and benefit from talking about it. The study confirms previous research indicating that talking about IPV experiences sometimes leads to feelings of relief in children. Thereby, professionals play an important role by providing an appropriate setting to help children reduce their distressing feelings. PMID- 26993037 TI - Texas anesthesiologist who billed when off work is convicted of defrauding insurers. PMID- 26993039 TI - Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. METHODS: Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test. KEY RESULTS: As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS diarrhea [IBS-D], IBS-constipation plus mixed [IBS-CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS-CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS-CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. CONCLUSIONS & INFERENCES: Despite similar levels of abdominal pain in IBS, the IBS-CM group demonstrated greater sensitivity to both thermal and visceral testing procedures. PMID- 26993040 TI - Genetically humanized pigs exclusively expressing human insulin are generated through custom endonuclease-mediated seamless engineering. PMID- 26993041 TI - Kindlin1 regulates microtubule function to ensure normal mitosis. AB - Loss of Kindlin 1 (Kin1) results in the skin blistering disorder Kindler Syndrome (KS), whose symptoms also include skin atrophy and reduced keratinocyte proliferation. Kin1 binds to integrins to modulate their activation and more recently it has been shown to regulate mitotic spindles and cell survival in a Plk1-dependent manner. Here we report that short-term Kin1 deletion in mouse skin results in impaired mitosis, which is associated with reduced acetylated tubulin (ac-tub) levels and cell proliferation. In cells, impaired mitosis and reduced ac tub levels are also accompanied by reduced microtubule stability, all of which are rescued by HDAC6 inhibition. The ability of Kin1 to regulate HDAC6-dependent cellular ac-tub levels is dependent on its phosphorylation by Plk1. Taken together, these data define a novel role for Kin1 in microtubule acetylation and stability and offer a mechanistic insight into how certain KS phenotypes, such as skin atrophy and reduced cell proliferation, arise. PMID- 26993042 TI - Discovering a critical transition state from nonalcoholic hepatosteatosis to nonalcoholic steatohepatitis by lipidomics and dynamical network biomarkers. AB - Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for type 2 diabetes and metabolic syndrome. However, accurately differentiating nonalcoholic steatohepatitis (NASH) from hepatosteatosis remains a clinical challenge. We identified a critical transition stage (termed pre-NASH) during the progression from hepatosteatosis to NASH in a mouse model of high fat-induced NAFLD, using lipidomics and a mathematical model termed dynamic network biomarkers (DNB). Different from the conventional biomarker approach based on the abundance of molecular expressions, the DNB model exploits collective fluctuations and correlations of different metabolites at a network level. We found that the correlations between the blood and liver lipid species drastically decreased after the transition from steatosis to NASH, which may account for the current difficulty in differentiating NASH from steatosis based on blood lipids. Furthermore, most DNB members in the blood circulation, especially for triacylglycerol (TAG), are also identified in the liver during the disease progression, suggesting a potential clinical application of DNB to diagnose NASH based on blood lipids. We further identified metabolic pathways responsible for this transition. Our study suggests that the transition from steatosis to NASH is not smooth and the existence of pre-NASH may be partially responsible for the current clinical limitations to diagnose NASH. If validated in humans, our study will open a new avenue to reliably diagnose pre-NASH and achieve early intervention of NAFLD. PMID- 26993043 TI - The FGF21-adiponectin axis in controlling energy and vascular homeostasis. AB - Whole-body energy metabolism and cardiovascular homeostasis are tightly controlled processes that involve highly coordinated crosstalk among distal organs. This is mainly achieved by a large number of hormones released from each organ. Among them, fibroblast growth factor 21 (FGF21) and adiponectin have recently gained considerable attention, since both of them possess multiple profound protective effects against a myriad of cardio-metabolic disorders. Despite their distinct structures and production sites, these two hormones share striking functional similarity. This dichotomy is recently reconciled by the demonstration of the FGF21-adiponectin axis. In adipocytes, both transcription and secretion of adiponectin are strongly induced by FGF21, which is partially dependent on PPARgamma activity. Furthermore, the glucose-lowering, lipid clearing, and anti-atherosclerotic functions of FGF21 are diminished in adiponectin-null mice, suggesting that adiponectin serves as an obligatory mediator of FGF21-elicited metabolic and vascular benefits. However, in both animals and human subjects with obesity, circulating FGF21 levels are increased whereas plasma adiponectin concentrations are reduced, perhaps due to FGF21 resistance, suggesting that dysfunctional FGF21-adiponectin axis is an important contributor to the pathogenesis of obesity-related cardio-metabolic syndrome. The FGF21-adiponectin axis protects against a cluster of cardio-metabolic disorders via mediating multi-organ communications, and is a promising target for therapeutic interventions of these chronic diseases. PMID- 26993045 TI - Adiponectin: a versatile player of innate immunity. AB - Adiponectin acts as a key regulator of the innate immune system and plays a major role in the progression of inflammation and metabolic disorders. Macrophages and monocytes are representative components of the innate immune system, and their proliferation, plasticity, and polarization are a key component of metabolic adaption. Innate-like lymphocytes such as group 2 innate lymphoid cells (ILC2s), natural killer T (NKT) cells, and gamma delta T (gammadelta T) cells are also members of the innate immune system and play important roles in the development of obesity and its related diseases. Adiponectin senses metabolic stress and modulates metabolic adaption by targeting the innate immune system under physiological and pathological conditions. Defining the mechanisms underlying the role of adiponectin in regulating innate immunity is crucial to adiponectin-based therapeutic intervention. PMID- 26993044 TI - Adiponectin signaling and function in insulin target tissues. AB - Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide, posing a major threat on human health, productivity, and quality of life. Despite great progress made towards a better understanding of the molecular basis of diabetes, the available clinical counter-measures against insulin resistance, a defect that is central to obesity-linked type 2 diabetes, remain inadequate. Adiponectin, an abundant adipocyte-secreted factor with a wide range of biological activities, improves insulin sensitivity in major insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism. However, adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention, and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation, and reveal therapeutic targets. Here, we discuss tissue- and cell-specific functions of adiponectin, with an emphasis on the regulation of adiponectin signaling pathways, and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation. Understanding better just why and how adiponectin and its downstream effector molecules work will be essential, together with empirical trials, to guide us to therapies that target the root cause(s) of type 2 diabetes and insulin resistance. PMID- 26993047 TI - Adiponectin, the past two decades. AB - Adiponectin is an adipocyte-specific factor, first described in 1995. Over the past two decades, numerous studies have elucidated the physiological functions of adiponectin in obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease. Adiponectin, elicited through cognate receptors, suppresses glucose production in the liver and enhances fatty acid oxidation in skeletal muscle, which together contribute to a beneficial metabolic action in whole body energy homeostasis. Beyond its role in metabolism, adiponectin also protects cells from apoptosis and reduces inflammation in various cell types via receptor-dependent mechanisms. Adiponectin, as a fat-derived hormone, therefore fulfills a critical role as an important messenger to communicate between adipose tissue and other organs. A better understanding of adiponectin actions, including the pros and cons, will advance our insights into basic mechanisms of metabolism and inflammation, and potentially pave the way toward novel means of pharmacological intervention to address pathophysiological changes associated with diabetes, atherosclerosis, and cardiometabolic disease. PMID- 26993046 TI - The tumor suppressor ING1b is a novel corepressor for the androgen receptor and induces cellular senescence in prostate cancer cells. AB - The androgen receptor (AR) signaling is critical for prostate cancer (PCa) progression to the castration-resistant stage with poor clinical outcome. Altered function of AR-interacting factors may contribute to castration-resistant PCa (CRPCa). Inhibitor of growth 1 (ING1) is a tumor suppressor that regulates various cellular processes including cell proliferation. Interestingly, ING1 expression is upregulated in senescent primary human prostate cells; however, its role in AR signaling in PCa was unknown. Using a proteomic approach by surface enhanced laser desorption ionization-mass spectrometry (SELDI-MS) combined with immunological techniques, we provide here evidence that ING1b interacts in vivo with the AR. The interaction was confirmed by co-immunoprecipitation, in vitro GST-pull-down, and quantitative intracellular colocalization analyses. Functionally, ING1b inhibits AR-responsive promoters and endogenous key AR target genes in the human PCa LNCaP cells. Conversely, ING1b knockout (KO) mouse embryonic fibroblasts (MEFs) exhibit enhanced AR activity, suggesting that the interaction with ING1b represses the AR-mediated transcription. Also, data suggest that ING1b expression is downregulated in CRPCa cells compared with androgen-dependent LNCaP cells. Interestingly, its ectopic expression induces cellular senescence and reduces cell migration in both androgen-dependent and CRPCa cells. Intriguingly, ING1b can also inhibit androgen-induced growth in LNCaP cells in a similar manner as AR antagonists. Moreover, ING1b upregulates different cell cycle inhibitors including p27(KIP1), which is a novel target for ING1b. Taken together, our findings reveal a novel corepressor function of ING1b on various AR functions, thereby inhibiting PCa cell growth. PMID- 26993049 TI - The role of music in the lives of older adults with dementia ageing in place: A scoping review. AB - The number of people around the world living with dementia is predicted to rise from 44 million to 135 million by 2050. Traditional treatments for dementia have been largely unsuccessful and prompted the emergence of alternative strategies. Music is emerging as an effective therapeutic strategy for older adults with dementia however, most of the work to date has focused on institutions. The purpose of this scoping review was to summarize what is known about the role and impact that music plays in the lives of community-dwelling older adults with dementia. Using a five-stage framework for conducting a scoping review, analysis revealed three ways in which music influences the lives of community-dwelling older adults with dementia: (a) reduced agitation, (b) improved cognition, and (c) enhanced social well-being. The concept of personhood provided a lens with which to conceptualize the findings and highlights the need for continued research. PMID- 26993048 TI - Comparison of prognoses according to non-positive and positive spectrin alphaII expression detected immunohistochemically in epithelial ovarian carcinoma: a retrospective study. AB - Anticancer drug sensitivity affects prognosis in ovarian carcinoma. Previously, we purified spectrin alphaII and betaII tetramers from cisplatin-resistant ovarian serous adenocarcinoma cells and demonstrated that they contribute to platinum anticancer drug resistance. In this clinical study, we focused on the role of spectrin alphaII expression. It is our objective to demonstrate the potential of spectrin alphaII expression as a useful predictor of anticancer drug resistance and postoperative prognosis in epithelial ovarian carcinoma. Spectrin alphaII expression in the ovarian adenocarcinoma surgical specimens of 193 patients was examined by immunohistochemical staining. Staining strength was scored 3+, regarded as positive expression, and 2+, 1+, and 0, regarded as non positive expression. Prognoses obtained from clinical records were evaluated by statistical analysis. In the 193 cases studied, positive spectrin alphaII expression was associated with worse overall survival when compared with non positive expression (P < 0.001 by log-rank test), and spectrin alphaII expression was identified as an independent predictive factor of overall survival (hazard ratio[HR]: 3.77, 95% confidence interval[CI]: 1.77-8.00; P < 0.001 by multivariate Cox's proportional hazards model). In the study about progression free survival, spectrin alphaII expression was not associated with prognoses. However, similar results as overall survival were obtained for survival after recurrence of the 92 recurrent cases (P = 0.0051 by log-rank test, HR: 4.49, 95% CI: 2.06-9.79; P < 0.001 by multivariate Cox's proportional hazards model). In a detailed overall survival study of 66 serous adenocarcinoma patients and 127 nonserous adenocarcinoma patients, similar results were also obtained. Spectrin alphaII expression is a useful predictor of anticancer drug resistance and postoperative prognosis in epithelial ovarian carcinoma.. PMID- 26993050 TI - Gan-Lu-Siao-Du-yin, a prescription of traditional Chinese medicine, inhibited enterovirus 71 replication, translation, and virus-induced cell apoptosis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Gan-Lu-Siao-Du-yin (GLSDY) is a prescription of traditional Chinese medicine. GLSDY contains 11 ingredients and is commonly used for endemic diseases. Enterovirus 71 (EV71) is an endemic disease that can cause meningoencephalitis with mortality and neurologic sequelae without any effective management. It is unknown whether GLSDY is effective against EV71 infection. AIM OF THE STUDY: To test the hypothesis that GLSDY can protect cell from EV71 induced injury. MATERIALS AND METHODS: Effects of a hot water extract of GLSDY on EV71 were tested in human foreskin fibroblast cells (CCFS-1/KMC) and human rhabdomyosarcoma cells (RD cells) by plaque reduction assay and flow cytometry respectively. Inhibition of viral replication was further examined by reverse quantitative RT-PCR (qRT-PCR). Its effect on viral protein translation and virus induced apoptosis were examined by western blot. RESULTS: GLSDY was dose dependently effective against EV71 infection (p<0.0001) in both CCFS-1/KMC cells and RD cells. GLSDY was highly effective when supplemented after viral inoculation (P<0.0001) with an IC50 of 8.7MUg/mL. GLSDY inhibited viral RNA replication (P<0.0001), formation of viral structural proteins (VP0, VP1, VP2 and VP3) and non-structural proteins (protease 2B and 3AB). Furthermore, 300MUg/mL GLSDY is effective to inhibit virus-induced apoptosis possibly through direct inhibition of caspase-8 and indirectly by inhibition of Bax. CONCLUSIONS: GLSDY is cheap and readily available to manage EV71 infection by inhibiting viral replication, viral protein formations, and EV71-induced apoptosis. PMID- 26993051 TI - Assessment of an aqueous seed extract of Parkia clappertoniana on reproductive performance and toxicity in rodents. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Parkia clappertoniana Keay (Family: Fabaceae) are extensively used in food in the form of a local condiment called 'Dawadawa' in Ghana and consumed by all class of people including sensitive groups such as pregnant women and children. Also, crudely pounded preparations of P. clappertoniana seeds are used as labor inducing agent in farm animals by local farmers across northern Ghana where nomadism is the livelihood of most indigenes. Ecologically, P. clappertoniana is extensively distributed across the savannah ecological zone of many African countries where just like Ghana it enjoys ethnobotanical usage. Although, many studies have investigated some aspects of the pharmacological activity of P. clappertoniana, none of these studies focused on the reproductive system, particularly its effects on reproductive performance and toxicity. To contribute, this study assessed the effect of aqueous seed extract of P. clappertoniana (PCE) on reproductive performance and toxicity in Sprague-Dawley rats and ICR mice. METHODS: After preparation of PCE, it was then tested on rodents at different gestational and developmental windows (1-7, 8-14, and 15-term gestational days) to assess the following: mating behavior, implantation rate, maternal and developmental toxicities. Generally, animals were randomly grouped into five and treated as follows: normal saline group (5ml/kg po), cytotec (misoprostol) group (200mg/kg po), folic acid group (5mg/kg po), and PCE groups (100, 200, and 500mg/kg po), however, these groupings were varied to suit the specific requirements of some parameters. For acute toxicity, animals were orally administered PCE (3 and 5g/kg for mice and rats respectively). RESULTS: PCE-treated rats showed improved mating behavior compared to control rats. PCE improved implantation rate compared to misoprostol-treated rats. On the average, PCE-treated rats delivered termed live pubs at 21 days compared to that of folic acid-treated rats at 23 days. Also, PCE-treated rats showed no observable maternal and developmental toxicities compared to folic acid and control rats. PCE (3-5g/kg po) was orally tolerated in rodents. CONCLUSION: Oral administration of Parkia clappertoniana seed extract improves reproductive performance in rodents with no observable maternal and developmental toxicity. PMID- 26993053 TI - Cerebral blood flow regulation, exercise and pregnancy: why should we care? AB - Cerebral blood flow (CBF) regulation is an indicator of cerebrovascular health increasingly recognized as being influenced by physical activity. Although regular exercise is recommended during healthy pregnancy, the effects of exercise on CBF regulation during this critical period of important blood flow increase and redistribution remain incompletely understood. Moreover, only a few studies have evaluated the effects of human pregnancy on CBF regulation. The present work summarizes current knowledge on CBF regulation in humans at rest and during aerobic exercise in relation to healthy pregnancy. Important gaps in the literature are highlighted, emphasizing the need to conduct well-designed studies assessing cerebrovascular function before, during and after this crucial life period to evaluate the potential cerebrovascular risks and benefits of exercise during pregnancy. PMID- 26993052 TI - Therapeutic targeting of two-pore-domain potassium (K(2P)) channels in the cardiovascular system. AB - The improvement of treatment strategies in cardiovascular medicine is an ongoing process that requires constant optimization. The ability of a therapeutic intervention to prevent cardiovascular pathology largely depends on its capacity to suppress the underlying mechanisms. Attenuation or reversal of disease specific pathways has emerged as a promising paradigm, providing a mechanistic rationale for patient-tailored therapy. Two-pore-domain K(+) (K(2P)) channels conduct outward K(+) currents that stabilize the resting membrane potential and facilitate action potential repolarization. K(2P) expression in the cardiovascular system and polymodal K2P current regulation suggest functional significance and potential therapeutic roles of the channels. Recent work has focused primarily on K(2P)1.1 [tandem of pore domains in a weak inwardly rectifying K(+) channel (TWIK)-1], K(2P)2.1 [TWIK-related K(+) channel (TREK)-1], and K(2P)3.1 [TWIK-related acid-sensitive K(+) channel (TASK)-1] channels and their role in heart and vessels. K(2P) currents have been implicated in atrial and ventricular arrhythmogenesis and in setting the vascular tone. Furthermore, the association of genetic alterations in K(2P)3.1 channels with atrial fibrillation, cardiac conduction disorders and pulmonary arterial hypertension demonstrates the relevance of the channels in cardiovascular disease. The function, regulation and clinical significance of cardiovascular K(2P) channels are summarized in the present review, and therapeutic options are emphasized. PMID- 26993054 TI - Prenatal diagnosis of hemoglobinopathies in Tunisia: an 18 years of experience. AB - Hemoglobinopathies are the most common genetic disease in Tunisia with a total carrier prevalence of 4.48%. OBJECTIVE: The aim of this study was to report an 18 year fully achieved experience of prenatal diagnosis (PND) of hemoglobinopathies (1994-2012) and to assess the impact of this prevention program. PATIENT AND METHODS: A total of 461 fetuses of 340 at-risk couples have been the subject of PND for beta-thalassemia major risk (41%), for sickle cell anemia risk (40.3%), for S/beta-thal risk (14.7%). The remainder fetuses were at risk for a compound heterozygote hemoglobinopathies (S/O, O/beta-thal, S/C....). Fetal DNA was studied by PCR procedure including the reverse dot-blot technique and the amplification refractory mutation system and direct sequencing. RESULTS AND DISCUSSION: Only 13.8% of the fetal samplings were conducted by chorionic villus sampling. The molecular result for beta-thalassemia risk has shown 13 beta-thal mutations, with two common: codon 39 (C>T) and IVS1-110 (G>A). The last 3 years, STR study has permitted to reduce the problems of maternal cell contamination. Among the 461 tested fetuses, 121 were affected, and then the pregnancy was terminated except for 13 cases, because of religious considerations and this despite the abortion legality in Tunisia. The conducted PND is only about 30 PND per year corresponding essentially to the couples living in Tunis City and surrounding area. PND number has increased from 1994 to 2009. This evolution has brutally decreased after the Tunisian revolution (2010). CONCLUSION: Although the good running of the PND, it covers only the Tunis city with low impact because it prevent apparition of only a mean of 7.3% of new cases. The reduced number of PND is not a technical inconvenience but rather a lack of a preventive program. PMID- 26993055 TI - Diffusion of antimicrobials in multispecies biofilms evaluated in a new biofilm model. AB - AIM: To describe the application of a newly-developed in vitro model in which the diffusion of antimicrobials in oral biofilms can be studied. METHODOLOGY: In a flow chamber consisting of three parallel feeding channels connected with each other by eight perpendicular side channels, multispecies biofilms were grown from saliva of a single donor for 48 h. The dimensions of the side channels were 100 MUm * 100 MUm * 5130 MUm (H * W * L). When one or more side channels were filled with biofilm, the biofilms were stained with fluorescent stains. Then, one side channel biofilm was selected and treated with phosphate buffered saline, 2% sodium hypochlorite (NaOCl), 17% ethylenediaminetetra-acetic acid (EDTA) or modified salt solution (MSS). Diffusion of the irrigants was observed by acquiring fluorescence images at 10* objective every 15 s for 30 min. RESULTS: It was possible to culture biofilms in the narrow (100 MUm) channels. The biofilms varied in phenotype. In this model, no diffusion of NaOCl into the biofilms was seen after its application. Seventeen-percentage EDTA only diffused into the biofilm up to 200 MUm in 30 min. MSS did diffuse in the biofilm over a distance of 450 MUm within 2 min after a single application. CONCLUSIONS: This new model enables the investigation of the diffusion of antimicrobials in biofilms. Other applications to improve our understanding of the characteristics of biofilms are now possible. PMID- 26993056 TI - The totally thoracoscopic left atrial maze procedure for the treatment of atrial fibrillation. AB - The totally thoracoscopic left atrial maze (TT-maze) is a recent, minimally invasive surgical procedure for the treatment of atrial fibrillation, with promising results in terms of freedom from atrial fibrillation. The TT-maze consists of a bilateral, epicardial pulmonary vein isolation with the creation of a box using radiofrequency and exclusion of the left atrial appendage (LAA). In addition, the box is connected with the base of the LAA and furthermore with the mitral annulus with the so-called trigonum line. In this report, we describe our surgical approach and short-term results. PMID- 26993057 TI - Anti-melanogenic effects of Aster spathulifolius extract in UVB-exposed C57BL/6J mice and B16F10 melanoma cells through the regulation of MAPK/ERK and AKT/GSK3beta signalling. AB - OBJECTIVES: Pharmacological studies of Aster spathulifolius Maxim(AS) have demonstrated its anti-allergy, anti-viral and anti-obesity effects, however, its anti-melanogenic effects is still unclear. In this study, the effects of AS extract (ASE) on the inhibition of melanin synthesis were investigated in vitro and in vivo. METHODS: To perform this study, the contents of melanin and tyrosinase activity were analysed in B16F10 melanoma cells. Western blotting was carried out to determine the underlyling mechanism. Additionally, we investigated the effect of this extract on hyperpigmentation in C57bL/6J mice induced by 3, 6 and 9 weeks of UVB irradiation. KEY FINDINGS: AS extract led to reduced melanin synthesis through the regulation of MITF and its downstream signals. Furthermore, ASE increased the phosphorylation of MAPK/ERK and Akt/GSK3beta signalling pathway components. In vivo study, hypopigmentation effects were also observed. The melanocyte activity and the distribution of melanin granules were decreased in UVB-irradiated mice treated with ASE. CONCLUSIONS: These results suggest that the ASE may be promising as an active anti-melanogenic component, and further investigations should be performed regarding its potential as a whitening agent in the field of cosmetics. PMID- 26993059 TI - MRI-derived bound and pore water concentrations as predictors of fracture resistance. AB - Accurately predicting fracture risk in the clinic is challenging because the determinants are multi-factorial. A common approach to fracture risk assessment is to combine X-ray-based imaging methods such as dual-energy X-ray absorptiometry (DXA) with an online Fracture Risk Assessment Tool (FRAX) that includes additional risk factors such as age, family history, and prior fracture incidents. This approach still does not adequately diagnose many individuals at risk, especially those with certain diseases like type 2 diabetes. As such, this study investigated bound water and pore water concentrations (Cbw and Cpw) from ultra-short echo time (UTE) magnetic resonance imaging (MRI) as new predictors of fracture risk. Ex vivo cadaveric arms were imaged with UTE MRI as well as with DXA and high-resolution micro-computed tomography (MUCT), and imaging measures were compared to both whole-bone structural and material properties as determined by three-point bending tests of the distal-third radius. While DXA-derived areal bone mineral density (aBMD) and MUCT-derived volumetric BMD correlated well with structural strength, they moderately correlated with the estimate material strength with gender being a significant covariate for aBMD. MRI-derived measures of Cbw and Cpw had a similar predictive ability of material strength as aBMD but did so independently of gender. In addition, Cbw was the only imaging parameter to significantly correlate with toughness, the energy dissipated during fracture. Notably, the strength of the correlations with the material properties of bone tended to be higher when a larger endosteal region was used to determine Cbw and Cpw. These results indicate that MRI measures of Cbw and Cpw have the ability to probe bone material properties independent of bone structure or subject gender. In particular, toughness is a property of fracture resistance that is not explained by X-ray based methods. Thus, these MRI-derived measures of Cbw and Cpw in cortical bone have the potential to be useful in clinical populations for evaluating fracture risk, especially involving diseases that affect material properties of the bone beyond its strength. PMID- 26993060 TI - Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2-selective antagonist idasanutlin (RG7388). AB - OBJECTIVES: To investigate whether the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) combined with the selective MDM2 antagonist idasanutlin (RG7388) offers superior efficacy to monotherapy in treating B-lymphoid malignancies in preclinical models. METHODS: The combined effect of obinutuzumab or rituximab plus idasanutlin on direct cell death/apoptosis induction and antibody-dependent cellular cytotoxicity (ADCC) was evaluated using p53 wild-type Z-138 and DoHH-2 lymphoma cells. Furthermore, whole blood B-cell depletion was analysed, and tumour growth inhibition was evaluated in subcutaneous xenograft models. RESULTS: Idasanutlin induced concentration dependent death of Z-138 and DoHH-2 cells. At concentrations >10-100 nm, idasanutlin enhanced obinutuzumab-induced death of DoHH-2 and Z-138 cells without negatively impacting obinutuzumab-mediated ADCC, natural killer cell activation or whole blood B-cell depletion. In the Z-138 xenograft model, a suboptimal dose of obinutuzumab with idasanutlin yielded substantial tumour growth inhibition and prolonged survival in a time-to-event analysis. In the DoHH-2 model, idasanutlin plus obinutuzumab showed superior tumour growth inhibition to idasanutlin plus rituximab. CONCLUSIONS: Obinutuzumab plus idasanutlin enhanced cell death of p53 wild-type tumour cells vs. rituximab plus idasanutlin without affecting obinutuzumab-mediated ADCC or B-cell depletion and showed robust antitumour efficacy in xenograft models, strongly supporting the investigation of this combination in clinical trials. PMID- 26993061 TI - Accounting for selection and correlation in the analysis of two-stage genome-wide association studies. AB - The problem of selection bias has long been recognized in the analysis of two stage trials, where promising candidates are selected in stage 1 for confirmatory analysis in stage 2. To efficiently correct for bias, uniformly minimum variance conditionally unbiased estimators (UMVCUEs) have been proposed for a wide variety of trial settings, but where the population parameter estimates are assumed to be independent. We relax this assumption and derive the UMVCUE in the multivariate normal setting with an arbitrary known covariance structure. One area of application is the estimation of odds ratios (ORs) when combining a genome-wide scan with a replication study. Our framework explicitly accounts for correlated single nucleotide polymorphisms, as might occur due to linkage disequilibrium. We illustrate our approach on the measurement of the association between 11 genetic variants and the risk of Crohn's disease, as reported in Parkes and others (2007. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat. Gen. 39: (7), 830-832.), and show that the estimated ORs can vary substantially if both selection and correlation are taken into account. PMID- 26993062 TI - Bayesian non-parametric inference for stochastic epidemic models using Gaussian Processes. AB - This paper considers novel Bayesian non-parametric methods for stochastic epidemic models. Many standard modeling and data analysis methods use underlying assumptions (e.g. concerning the rate at which new cases of disease will occur) which are rarely challenged or tested in practice. To relax these assumptions, we develop a Bayesian non-parametric approach using Gaussian Processes, specifically to estimate the infection process. The methods are illustrated with both simulated and real data sets, the former illustrating that the methods can recover the true infection process quite well in practice, and the latter illustrating that the methods can be successfully applied in different settings. PMID- 26993058 TI - Monocarboxylate transporters in the brain and in cancer. AB - Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID- 26993063 TI - Synergistic Inhibitory Effects of Hypoxia and Iron Deficiency on Hepatic Glucose Response in Mouse Liver. AB - Hypoxia and iron both regulate metabolism through multiple mechanisms, including hypoxia-inducible transcription factors. The hypoxic effects on glucose disposal and glycolysis are well established, but less is known about the effects of hypoxia and iron deficiency on hepatic gluconeogenesis. We therefore assessed their effects on hepatic glucose production in mice. Weanling C57BL/6 male mice were fed an iron-deficient (4 ppm) or iron-adequate (35 ppm) diet for 14 weeks and were continued in normoxia or exposed to hypoxia (8% O2) for the last 4 weeks of that period. Hypoxic mice became hypoglycemic and displayed impaired hepatic glucose production after a pyruvate challenge, an effect accentuated by an iron deficient diet. Stabilization of hypoxia-inducible factors under hypoxia resulted in most glucose being converted into lactate and not oxidized. Hepatic pyruvate concentrations were lower in hypoxic mice. The decreased hepatic pyruvate levels were not caused by increased utilization but rather were contributed to by decreased metabolism from gluconeogenic amino acids. Pyruvate carboxylase, which catalyzes the first step of gluconeogenesis, was also downregulated by hypoxia with iron deficiency. Hypoxia, and more so hypoxia with iron deficiency, results in hypoglycemia due to decreased levels of hepatic pyruvate and decreased pyruvate utilization for gluconeogenesis. These data highlight the role of iron levels as an important determinant of glucose metabolism in hypoxia. PMID- 26993065 TI - [11C]-Labeled Metformin Distribution in the Liver and Small Intestine Using Dynamic Positron Emission Tomography in Mice Demonstrates Tissue-Specific Transporter Dependency. AB - Metformin is the most commonly prescribed oral antidiabetic drug, with well documented beneficial preventive effects on diabetic complications. Despite being in clinical use for almost 60 years, the underlying mechanisms for metformin action remain elusive. Organic cation transporters (OCT), including multidrug and toxin extrusion proteins (MATE), are essential for transport of metformin across membranes, but tissue-specific activity of these transporters in vivo is incompletely understood. Here, we use dynamic positron emission tomography with [(11)C]-labeled metformin ([(11)C]-metformin) in mice to investigate the role of OCT and MATE in a well-established target tissue, the liver, and a putative target of metformin, the small intestine. Ablation of OCT1 and OCT2 significantly reduced the distribution of metformin in the liver and small intestine. In contrast, inhibition of MATE1 with pyrimethamine caused accumulation of metformin in the liver but did not affect distribution in the small intestine. The demonstration of OCT-mediated transport into the small intestine provides evidence of direct effects of metformin in this tissue. OCT and MATE have important but separate roles in uptake and elimination of metformin in the liver, but this is not due to changes in biliary secretion. [(11)C]-Metformin holds great potential as a tool to determine the pharmacokinetic properties of metformin in clinical studies. PMID- 26993064 TI - Growth and Risk for Islet Autoimmunity and Progression to Type 1 Diabetes in Early Childhood: The Environmental Determinants of Diabetes in the Young Study. AB - Increased growth in early childhood has been suggested to increase the risk of type 1 diabetes. This study explored the relationship between weight or height and development of persistent islet autoimmunity and progression to type 1 diabetes during the first 4 years of life in 7,468 children at genetic risk for type 1 diabetes followed in Finland, Germany, Sweden, and the U.S. Growth data collected every third month were used to estimate individual growth curves by mixed models. Cox proportional hazards models were used to evaluate body size and risk of islet autoimmunity and type 1 diabetes. In the overall cohort, development of islet autoimmunity (n = 575) was related to weight z scores at 12 months (hazard ratio [HR] 1.16 per 1.14 kg in males or per 1.02 kg in females, 95% CI 1.06-1.27, P < 0.001, false discovery rate [FDR] = 0.008) but not at 24 or 36 months. A similar relationship was seen between weight z scores and development of multiple islet autoantibodies (1 year: HR 1.21, 95% CI 1.08-1.35, P = 0.001, FDR = 0.008; 2 years: HR 1.18, 95% CI 1.06-1.32, P = 0.004, FDR = 0.02). No association was found between weight or height and type 1 diabetes (n = 169). In conclusion, greater weight in the first years of life was associated with an increased risk of islet autoimmunity. PMID- 26993066 TI - Increased Expression of the Diabetes Gene SOX4 Reduces Insulin Secretion by Impaired Fusion Pore Expansion. AB - The transcription factor Sox4 has been proposed to underlie the increased type 2 diabetes risk linked to an intronic single nucleotide polymorphism in CDKAL1 In a mouse model expressing a mutant form of Sox4, glucose-induced insulin secretion is reduced by 40% despite normal intracellular Ca(2+) signaling and depolarization-evoked exocytosis. This paradox is explained by a fourfold increase in kiss-and-run exocytosis (as determined by single-granule exocytosis measurements) in which the fusion pore connecting the granule lumen to the exterior expands to a diameter of only 2 nm, which does not allow the exit of insulin. Microarray analysis indicated that this correlated with an increased expression of the exocytosis-regulating protein Stxbp6. In a large collection of human islet preparations (n = 63), STXBP6 expression and glucose-induced insulin secretion correlated positively and negatively with SOX4 expression, respectively. Overexpression of SOX4 in the human insulin-secreting cell EndoC betaH2 interfered with granule emptying and inhibited hormone release, the latter effect reversed by silencing STXBP6 These data suggest that increased SOX4 expression inhibits insulin secretion and increased diabetes risk by the upregulation of STXBP6 and an increase in kiss-and-run exocytosis at the expense of full fusion. We propose that pharmacological interventions promoting fusion pore expansion may be effective in diabetes therapy. PMID- 26993068 TI - Differences in In Vivo Cellular Kinetics in Abdominal and Femoral Subcutaneous Adipose Tissue in Women. AB - The accumulation of fat in upper-body (abdominal) adipose tissue is associated with obesity-related cardiometabolic diseases, whereas lower-body (gluteal and femoral) fat may be protective. Studies suggest physiological and molecular differences between adipose depots and depot-specific cellular mechanisms of adipose expansion. We assessed in vivo cellular kinetics in subcutaneous adipose tissue from the abdominal (scABD) and femoral (scFEM) depots using an 8-week incorporation of deuterium ((2)H) from (2)H2O into the DNA of adipocytes and preadipocytes in 25 women with overweight or obesity. DNA synthesis rates denote new cell formation of preadipocytes and adipocytes in each depot. Formation of adipocytes was positively correlated to that of preadipocytes in the scABD and scFEM depots and was related to percent body fat in each depot. Notably, preadipocytes and adipocytes had higher formation rates in the scFEM depot relative to the scABD. This method to assess in vivo adipogenesis will be valuable to evaluate adipocyte kinetics in individuals with varying body fat distributions and degrees of metabolic health and in response to a variety of interventions, such as diet, exercise, or pharmacological treatment. PMID- 26993067 TI - The Genetic Program of Pancreatic beta-Cell Replication In Vivo. AB - The molecular program underlying infrequent replication of pancreatic beta-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating beta-cells and determined their transcriptome. Replicating beta-cells upregulate hundreds of proliferation related genes, along with many novel putative cell cycle components. Strikingly, genes involved in beta-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating beta-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in beta-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue specific genes, which are "left behind" and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating beta-cells in vivo. PMID- 26993070 TI - Brain Lactate Concentration Falls in Response to Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia. AB - Brain lactate may be involved in the development of impaired awareness of hypoglycemia (IAH), a condition that affects approximately 25% of patients with type 1 diabetes and increases the risk of severe hypoglycemia. The aim of this study was to investigate the effect of acute hypoglycemia on brain lactate concentration in patients with IAH as compared with those with normal awareness of hypoglycemia (NAH) and healthy control subjects (n = 7 per group). After an overnight fast, all subjects underwent a two-step hyperinsulinemic euglycemic (5.0 mmol/L)-hypoglycemic (2.8 mmol/L) glucose clamp. Brain lactate concentrations were measured continuously with (1)H-MRS using a specific lactate detection method. Hypoglycemia generated symptoms in patients with NAH and healthy control subjects but not in patients with IAH. Brain lactate fell significantly by ~20% in response to hypoglycemia in patients with type 1 diabetes with IAH but remained stable in both healthy control subjects and in patients with NAH. The fall in brain lactate is compatible with increased brain lactate oxidation providing an alternative fuel source during hypoglycemia, which may contribute to the impaired detection of hypoglycemia. PMID- 26993069 TI - IKKbeta Is Essential for Adipocyte Survival and Adaptive Adipose Remodeling in Obesity. AB - IkappaB kinase beta (IKKbeta), a central coordinator of inflammatory responses through activation of nuclear factor-kappaB (NF-kappaB), has been implicated as a critical molecular link between inflammation and metabolic disorders; however, the role of adipocyte IKKbeta in obesity and related metabolic disorders remains elusive. Here we report an essential role of IKKbeta in the regulation of adipose remodeling and adipocyte survival in diet-induced obesity. Targeted deletion of IKKbeta in adipocytes does not affect body weight, food intake, and energy expenditure but results in an exaggerated diabetic phenotype when challenged with a high-fat diet (HFD). IKKbeta-deficient mice have multiple histopathologies in visceral adipose tissue, including increased adipocyte death, amplified macrophage infiltration, and defective adaptive adipose remodeling. Deficiency of IKKbeta also leads to increased adipose lipolysis, elevated plasma free fatty acid (FFA) levels, and impaired insulin signaling. Mechanistic studies demonstrated that IKKbeta is a key adipocyte survival factor and that IKKbeta protects murine and human adipocytes from HFD- or FFA-elicited cell death through NF-kappaB-dependent upregulation of antiapoptotic proteins and NF-kappaB independent inactivation of proapoptotic BAD protein. Our findings establish IKKbeta as critical for adipocyte survival and adaptive adipose remodeling in obesity. PMID- 26993071 TI - Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data. AB - Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin concentration 37 pmol/L) were used. Endogenous insulin secretion (calculated by C-peptide deconvolution) and insulin infusion rates were used as inputs to a new two-compartment model of insulin kinetics and hepatic and extrahepatic clearance parameters were estimated. Good agreement between modeled and measured plasma insulin profiles was observed (mean normalized root mean square error 6.8%), and considerable intersubject variability in parameters of insulin clearance among individuals was identified (the mean [interquartile range] for hepatic extraction was 25.8% [32.7%], and for extrahepatic insulin clearance was 20.7 mL/kg/min [11.7 mL/kg/min]). Parameters of insulin clearance were correlated with measures of insulin sensitivity and acute insulin response to glucose. The method described appears promising for future research aimed at characterizing variability in insulin clearance and the mechanisms involved in the regulation of insulin clearance. PMID- 26993073 TI - Hand dominance in intravenous drug using patients does not affect peripheral venous access sites identified by ultrasound. AB - BACKGROUND: The peripheral veins in the arms and forearms of patients with a history of intravenous (IV) drug use may be sclerosed, calcified, or collapsed due to damage from previous injections. These patients may consequently require alternative, more invasive types of vascular access including central venous or intraosseous catheters. We investigated the relationship between hand dominance and the presence of patent upper extremity (UE) veins specifically in patients with a history of IV drug-use. We predicted that injection into the non-dominant UE would occur with a higher frequency than the dominant UE, leading to fewer damaged veins in the dominant UE. If hand dominance affects which upper extremity has more patent veins, providers could focus their first vascular access attempt on the dominant upper extremity. METHODS: Adult patients were approached for enrollment if they provided a history of IV drug use into one of their upper extremities. Each upper extremity was examined with a high frequency linear transducer in 3 areas: the antecubital crease, forearm and the proximal arm. The number of fully compressible veins >=1.8 mm in diameter was recorded for each location. RESULTS: The mean vein difference between the numbers of veins in the dominant versus the non-dominant UE was -1.5789. At a .05 significance level, there was insufficient evidence to suggest the number of compressible veins between patients' dominant and non-dominant arms was significantly different (P = .0872.) CONCLUSIONS: The number of compressible veins visualized with ultrasound was not greater in the dominant upper extremity as expected. Practitioners may gain more information about potential peripheral venous access sites by asking patients their previous injection practice patterns. PMID- 26993074 TI - Protective effects of cyclosporine A and hypothermia on neuronal mitochondria in a rat asphyxial cardiac arrest model. AB - BACKGROUND: Cyclosporine A (CsA) was neuroprotective in the settings of traumatic brain injury and stroke. We sought to investigate the protective effects of CsA and hypothermia on neuronal mitochondria after cardiac arrest. METHODS AND RESULTS: Five groups were included: sham (S), normothermia (N), CsA (C), hypothermia (H), and CsA plus hypothermia (C+H). Cardiac arrest was induced by 10min of asphyxia. CsA (10mg/kg) was administered immediately after return of spontaneous circulation in the CsA groups. Temperature of the rats was maintained at 33+/-0.5 degrees C after return of spontaneous circulation in the hypothermia groups. Hippocampal mitochondria were measured after 2h of resuscitation. Mitochondrial transmembrane potential was significantly higher in the C, the H, and the C+H groups than in the N group and was higher in the C+H group than in the C and the H groups. Cytosolic cytochrome c was significantly higher in the N group. Superoxide dismutase activity was significantly lower in the N group than in the other groups and was higher in the C and the C+H groups than in the H group. Malondialdehyde concentration was significantly higher in the N group. CONCLUSIONS: CsA or hypothermia used immediately after resuscitation enhanced mitochondrial transmembrane potential, kept cytochrome c from releasing out of the mitochondria, increased superoxide dismutase activity, and decreased malondialdehyde concentration in hippocampus. Moreover, the protective effects of CsA were reinforced by hypothermia. One of the mechanisms that hypothermia protected neuronal mitochondria from damage was inhibiting the opening of mitochondrial permeability transition pore. PMID- 26993075 TI - ED evaluation and management of implantable cardiac defibrillator electrical shocks. AB - Patients with implantable cardiac defibrillators not infrequently present to the emergency department after experiencing an implantable cardiac defibrillator shock. This review considers the management of such patients in the emergency department, including appropriate, inappropriate, and phantom shocks as well as electrical storm. PMID- 26993076 TI - Prolonged constant load cycling exercise is associated with reduced gross efficiency and increased muscle oxygen uptake. AB - This study investigated the effects of prolonged constant load cycling exercise on cycling efficiency and local muscle oxygen uptake responses. Fourteen well trained cyclists each completed a 2-h steady-state cycling bout at 60% of their maximal minute power output to assess changes in gross cycling efficiency (GE) and muscle oxygen uptake (mVO2 ) at time points 5, 30, 60, 90, and 120 min. Near infrared spatially resolved spectroscopy (NIRS) was used to continually monitor tissue oxygenation of the Vastus Lateralis muscle, with arterial occlusions (OCC) applied to assess mVO2 . The half-recovery time of oxygenated hemoglobin (HbO2 ) was also assessed pre and post the 2-h cycling exercise by measuring the hyperemic response following a 5-min OCC. GE significantly declined during the 2 h cycling bout (18.4 +/- 1.6 to 17.4 +/- 1.4%; P < 0.01). Conversely, mVO2 increased, being significantly higher after 90 and 120 min than at min 5 (+0.04 mlO2 /min/100 g; P = 0.03). The half-recovery time for HbO2 was increased comparing pre and post the 2-h cycling exercise (+7.1 +/- 19s), albeit not significantly (d: 0.48; P = 0.27). This study demonstrates that GE decreases during prolonged constant load cycling exercise and provides evidence of an increased mVO2 , suggestive of progressive mitochondrial or contractile inefficiency. PMID- 26993072 TI - Epithelial Junction Opener Improves Oncolytic Adenovirus Therapy in Mouse Tumor Models. AB - A central resistance mechanism in solid tumors is the maintenance of epithelial junctions between malignant cells that prevent drug penetration into the tumor. Human adenoviruses (Ads) have evolved mechanisms to breach epithelial barriers. For example, during Ad serotype 3 (Ad3) infection of epithelial tumor cells, massive amounts of subviral penton-dodecahedral particles (PtDd) are produced and released from infected cells to trigger the transient opening of epithelial junctions, thus facilitating lateral virus spread. We show here that an Ad3 mutant that is disabled for PtDd production is significantly less effective in killing of epithelial human xenograft tumors than the wild-type Ad3 virus. Intratumoral spread and therapeutic effect of the Ad3 mutant was enhanced by co administration of a small recombinant protein (JO; produced in Escherichia coli) that incorporated the minimal junction opening domains of PtDd. We then demonstrated that co-administration of JO with replication-competent Ads that do not produce PtDd (Ad5, Ad35) resulted in greater attenuation of tumor growth than virus injection alone. Furthermore, we genetically modified a conditionally replicating Ad5-based oncolytic Ad (Ad5Delta24) to express a secreted form of JO upon replication in tumor cells. The JO-expressing virus had a significantly greater antitumor effect than the unmodified AdDelta24 version. Our findings indicate that epithelial junctions limit the efficacy of oncolytic Ads and that this problem can be address by co-injection or expression of JO. JO has also the potential for improving cancer therapy with other types of oncolytic viruses. PMID- 26993077 TI - [Medical management of interstitiel pregnancy by in situ methotrexate]. AB - INTRODUCTION: Interstitial pregnancy accounts for 3 to 11% of ectopic pregnancy; these pregnancies are the more frequently non-tubal ectopic pregnancy. Medical treatment can be used in case of unruptured interstitial pregnancy and is used more and more frequently to avoid hemorrhagic risk and risk of conversion to radical surgery when a surgical management is decided. However, a larger use of methotrexate in interstitial pregnancy and conditions of use are not clearly defined. The aim of this study is to report a series of unruptured interstitial pregnancy managed by in situ injection of methotrexate. WOMEN AND METHODS: This retrospective observational study included women treated for an interstitial pregnancy between 2010 and 2013 in a teaching hospital. Medical management used was an in situ injection of methotrexate (1mg/kg) guided by vaginal sonography plus an intramuscular injection of methotrexate (1mg/kg) in the 48hours following in situ injection and 600mg of mifepristone when progesterone blood rate was more than 9ng/mL. A great decrease of serum hCG without surgery was considered a success. RESULTS: Fourteen women had an interstitial pregnancy during the study period. Six were managed surgically in 5 cases for suspicion of uterine rupture and one for pregnancy of unknown location. Eight women had a medical management and the success rate was 100%. Mean time for decrease of serum hCG until 2 UI/L was 54.4 days [34.0-74.8]. No uterine rupture or immediate complication was reported. Five women out of 8 had a spontaneous pregnancy after management of interstitial pregnancy. CONCLUSION: Medical management by in situ injection of methotrexate under sonographic guidance with an intramuscular injection within the 48hours following the in situ injection and mifepristone when ectopic pregnancy was active can be proposed in first-line therapy in case of unruptured interstitial pregnancy. This treatment has a great efficiency and low rate of complications. PMID- 26993078 TI - Biodistribution of the novel anticancer drug sodium trans-[tetrachloridobis(1H indazole)ruthenate(III)] KP-1339/IT139 in nude BALB/c mice and implications on its mode of action. AB - The ruthenium complex sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP-1339/IT139) has entered clinical trials as the more soluble alternative to the indazolium compound KP1019. In order to get insight into its distribution and accumulation throughout a living organism, KP-1339/IT139 was administered intravenously in non-tumor bearing nude BALB/c mice and the Ru content in blood cells and plasma, bone, brain, colon, kidneys, liver, lung, muscle, spleen, stomach and thymus was determined at several time points. The Ru concentration in blood cells and plasma was found to increase slightly within the first hours of analysis, with the Ru concentration being 3-times higher in plasma compared to blood cells. The plasma samples were subjected to analysis by capillary zone electrophoresis (CZE) and size exclusion/anion exchange chromatography (SEC-IC) both coupled to inductively coupled plasma-mass spectrometry (ICP-MS) and a large majority of the total Ru content was found attached to mouse serum albumin (MSA), confirming similar behavior to KP1019 in an in vivo setting. Within 1h, the peak ratio of approximately 1.2-1.5 Ru per albumin molecule was reached which declined to about 1 Ru per albumin molecule within 24h. Beside the MSA adduct a higher molecular weight species was observed probably stemming from MSA conjugates. In addition, the tissue samples were mineralized by microwave digestion and analyzed for their Ru content. The highest Ru levels were found in colon, lung, liver, kidney and notably in the thymus. The peak Ru concentrations in these tissues were reached 1-6h after administration and declined slowly over time. PMID- 26993079 TI - A novel dual-functioning ruthenium(II)-arene complex of an anti-microbial ciprofloxacin derivative - Anti-proliferative and anti-microbial activity. AB - 7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(eta(6)-p cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1.1.3H2O.0.6CH3OH and 2.CH3OH.0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) pi-bonded to the p-cymene ring and sigma-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low MUM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low MUM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation beta-lactam antibiotics. PMID- 26993080 TI - Melatonin pretreatment enhances the therapeutic effects of exogenous mitochondria against hepatic ischemia-reperfusion injury in rats through suppression of mitochondrial permeability transition. AB - We tested the hypothesis that melatonin (Mel) enhances exogenous mitochondria (Mito) treatment against rodent hepatic ischemia-reperfusion (IR) injury. In vitro study utilized three groups of hepatocytes (i.e. nontreatment, menadione, and menadione-melatonin treatment, 4.0 * 10(5) each), while in vivo study used adult male Sprague Dawley rats (n = 40) equally divided into sham-control (SC), IR (60-min left-lobe ischemia + 72-hr reperfusion), IR-Mel (melatonin at 30 min/6/8 hr after reperfusion), IR-Mito (mitochondria 15,000 MUg/rat 30 min after reperfusion), and IR-Mel-Mito. Following menadione treatment in vitro, oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved caspase-3/PARP), DNA damage (gamma-H2AX/CD90/XRCC1), mitochondria damage (cytosolic cytochrome c) biomarkers, and mitochondrial permeability transition were found to be lower, whereas mitochondrial cytochrome c were found to be higher in hepatocytes with melatonin treatment compared to those without (all P < 0.001). In vivo study demonstrated highest liver injury score and serum AST in IR group, but lowest in SC group and higher in IR-Mito group than that in groups IR-Mel and IR-Mel-Mito, and higher in IR-Mel group than that in IR-Mel-Mito group after 72-hr reperfusion (all P < 0.003). Protein expressions of inflammatory (TNF-alpha/NF-kappaB/IL 1beta/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase 3/PARP/Bax), and mitochondria damage (cytosolic cytochrome c) biomarkers displayed an identical pattern, whereas mitochondria integrity marker (mitochondrial cytochrome c) showed an opposite pattern compared to that of liver injury score (all P < 0.001) among five groups. Microscopically, expressions of apoptotic nuclei, inflammatory (MPO(+) /CD68(+) /CD14(+) cells), and DNA damage (gamma-H2AX(+) cells) biomarkers exhibited an identical pattern compared to that of liver injury score (all P < 0.001) among five groups. Melatonin-supported mitochondria treatment offered an additional benefit of alleviating hepatic IR injury. PMID- 26993081 TI - Relative plan robustness of step-and-shoot vs rotational intensity-modulated radiotherapy on repeat computed tomographic simulation for weight loss in head and neck cancer. AB - INTRODUCTION: Interfractional anatomical alterations may have a differential effect on the dose delivered by step-and-shoot intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). The increased degrees of freedom afforded by rotational delivery may increase plan robustness (measured by change in target volume coverage and doses to organs at risk [OARs]). However, this has not been evaluated for head and neck cancer. MATERIALS AND METHODS: A total of 10 patients who required repeat computed tomography (CT) simulation and replanning during head and neck IMRT were included. Step-and-shoot IMRT and VMAT plans were generated from the original planning scan. The initial and second CT simulation scans were fused and targets/OAR contours transferred, reviewed, and modified. The plans were applied to the second CT scan and doses recalculated without repeat optimization. Differences between step-and-shoot IMRT and VMAT for change in target volume coverage and doses to OARs between first and second CT scans were compared by Wilcoxon signed rank test. RESULTS: There were clinically relevant dosimetric changes between the first and the second CT scans for both the techniques (reduction in mean D95% for PTV2 and PTV3, Dmin for CTV2 and CTV3, and increased mean doses to the parotid glands). However, there were no significant differences between step-and-shoot IMRT and VMAT for change in any target coverage parameter (including D95% for PTV2 and PTV3 and Dmin for CTV2 and CTV3) or dose to any OARs (including parotid glands) between the first and the second CT scans. CONCLUSIONS: For patients with head and neck cancer who required replanning mainly due to weight loss, there were no significant differences in plan robustness between step-and-shoot IMRT and VMAT. This information is useful with increased clinical adoption of VMAT. PMID- 26993082 TI - Composition and biological activities of the essential oil of Piper corcovadensis (Miq.) C. DC (Piperaceae). AB - Essential oil from fresh leaves of the shrub Piper corcovadensis (Miq.) C. DC was obtained in 0.21% (w/w) yield by hydrodistillation in a Clevenger type apparatus. Thirty-one components, accounting for 96.61% of the leaf oil, were identified by gas chromatography-mass spectrometry. The major constituents of the oil were 1 butyl-3,4-methylenedioxybenzene (30.62%), terpinolene (17.44%), trans caryophyllene (6.27%), alpha-pinene (5.92%), delta-cadinene (4.92%), and Limonene (4.46%). Bioassays against larvae of the Dengue mosquito (Aedes aegypti) revealed that leaf oil (LC50 = 30.52 ppm), terpinolene (LC50 = 31.16 ppm), and pure 1 butyl-3,4-methylenedioxybenzene (LC50 = 22.1 ppm) possessed larvicidal activities and are able to interfere with the activity of proteases from L4 gut enzymes. Additionally, the essential oil exhibited a strong oviposition deterrent activity at 50 and 5 ppm. This paper constitutes the first report of biological activities associated with the essential oil of leaves of P. corcovadensis. PMID- 26993083 TI - Nest ecology of blood parasites in the European roller and its ectoparasitic carnid fly. AB - Haemosporidian parasites are considered the most important vector-borne parasites. However, vector identity and ecology is unknown for most such host vector-parasite systems. In this study, we employ microscopic and molecular analyses to examine haemosporidian prevalence in a migratory, cavity-nesting bird, European roller Coracias garrulus, and its nidicolous blood-feeding ectoparasite Carnus hemapterus. This system is unique in that the ectoparasite is confined to a near-closed environment, in contrast to the free-wandering system of haematophagous dipterans such as mosquitoes. Blood film analysis confirms previous works in that Haemoproteus parasites are widely prevalent in adult rollers and belong to a single species, Haemoproteus coraciae. Leucocytozoon sp. and Trypanosoma sp. also are detected in adult rollers at low intensities with this technique. By means of molecular analysis, we report for the first time Plasmodium sp. presence in C. garrulus. Based on PCR results, Plasmodium parasites are relatively less prevalent than Haemoproteus parasites (20% vs. 31%) in rollers. In contrast, haemosporidian prevalences show the opposite trend for Carnus flies: Plasmodium sp. occurrence (62%) clearly predominates over that of Haemoproteus sp. (5%). A comparison between roller and Carnus samples reveals a significantly higher prevalence of Plasmodium sp. in Carnus samples. Insect survey and phylogenetic analysis suggest Culicoides flies as Haemoproteus sp. vectors, which appear to readily transmit the parasite in southern Spain. This study does not find support for Carnus flies to serve as biological or mechanical vectors of haemosporidians. In spite of this, nidicolous blood-feeding ectoparasites, such as carnid flies, appear as a suitable model for studies on the occurrence and temporal dynamics of avian haemosporidians such as Plasmodium sp. present at low intensities. PMID- 26993084 TI - Kinetics of acute infection with Toxoplasma gondii and histopathological changes in the duodenum of rats. AB - Toxoplasma gondii crosses the intestinal barrier to spread into the body. We investigate the intestinal wall and epithelial cells of the duodenum of rats infected with T. gondii during different time points of acute infection. Male Wistar rats, 60 days of age, were assigned into groups that were orally inoculated with 5000 sporulated oocysts T. gondii for 6 h (G6), 12 h (G12), 24 h (G24), 48 h (G48), 72 h (G72), 7 days (G7d), and 10 days (G10d). The control group (CG) received saline. The rats were killed and the duodenum was processed to obtain histological sections stained with hematoxylin and eosin, Periodic Acid Schiff, and Alcian blue (pH 2.5 and 1.0). Morphometry was performed on the layers of the intestinal wall and enterocytes, and the number of goblet cells and intraepithelial lymphocytes was counted. The data were compared by ANOVA considering 5% as level of significance. The infection provoked an increase in the width of villi and crypts; decrease in enterocyte height; increase in the smaller-diameter and reduction in the larger-diameter of the enterocytes nuclei, increased number of goblet cells secreting neutral (G6, G12 and G7d) and acidic (G7d and G10d) mucus, and increase in the number of intraepithelial lymphocytes (G48). The infected groups showed atrophy of the submucosa and muscular layers and the total wall. Acute infection with T. gondii caused morphological changes in the intestinal wall and epithelial cells of the duodenum in rats. PMID- 26993085 TI - Antiparasitic effects of oxymatrine and matrine against Toxoplasma gondii in vitro and in vivo. AB - Toxoplasma gondii (T. gondii) is an important pathogen which can causes serious public health problems. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective and new substances of relatively low toxicity is urgently needed. This study was carried out to evaluate the anti-parasitic effect of oxymatrine (OM) and matrine (ME) against T. gondii in vitro and in vivo. In our study, the anti-T. gondii activities of ME and OM were evaluated in vitro using cell counting kit-8 assay, morphological observation and trypan blue exclusion assay. In vivo, mice were sacrificed four days post-infection and ascites were drawn out to determine the extent of tachyzoite proliferation. Viscera indexes and liver biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were examined to evaluate the toxicity of compounds to mice. As a result, OM and ME showed anti-T. gondii activity but low selectivity toxicity to HeLa cells. Both compounds also significantly decreased the number of tachyzoites in peritoneal cavity and recovered the levels of ALT, AST, GSH and MDA in liver. Moreover, the mice treated with OM or ME achieved better results in viscera index and survival rate than that of spiramycin. These results suggest that OM and ME are likely the sources of new drugs for toxoplasmosis, and further studies will be necessary to compare the efficacy of drug combination, as well as identify its action of mechanism. PMID- 26993086 TI - Generation and characterization of monoclonal antibodies specific for 18 kDa antigen from Taenia solium cysticerci. AB - The gene encoding a mature 18 kDa glycoprotein of Taenia solium cysticerci (Ts18) was cloned and bacterially expressed with a His-tagged fusion protein. Monoclonal antibodies (MAbs) against the recombinant Ts18 antigen were generated in vitro by routine murine hybridoma technique of fusing splenocytes, from BALB/c mice immunized with the vesicular fluid of T. solium cysticerci (TsVF), with mouse myeloma cells (SP2/0). The reactivity and specificity of these MAbs were evaluated by indirect ELISA and immunoblotting techniques. Three stable hybridoma clones, namely 3B11, 6C5, and 6G4, were screened using His-Ts18-based ELISA, and these showed two IgG1 isotypes and one IgM isotype. All MAbs reacted with His Ts18 at molecular weight (MW) 12.8 kDa and the native antigen at MW 18 kDa in TsVF and whole larval extracts (WLE). In a dot blotting test, MAbs 6C5 and 6G4 showed no obvious cross-reactivity with heterologous vesicular fluids from other taeniid species, including Taenia saginata (TsaVF), Taenia pisiformis (TpVF), Taenia hydatigena (ThVF), Taenia multiceps (TmVF), and Echinococcus granulosus (EgVF). Immunofluorescent assays showed that MAb 6C5 specifically reacted with the Ts18 expressed from pEGFP-N1-Ts18-transfected HeLa cells. Immunolocalization analysis, using MAb 6C5 as a probe, indicated that Ts18 was present at high concentrations in the region of the larval sucker and spiral canal. The results indicate that the Ts18 protein is an abundantly secreted parasite protein and MAbs against it might provide a step forward for improving the diagnosis of porcine cysticercosis. PMID- 26993087 TI - Brand New Medicine for an Older Society. PMID- 26993088 TI - Low-dose polymyxin: an option for therapy of Gram-negative sepsis. AB - Endotoxins are the major components of the outer membrane of most Gram-negative bacteria and are one of the main targets in inflammatory diseases. The presence of endotoxins in blood can provoke septic shock in case of pronounced immune response. Here we show in vitro inactivation of endotoxins by polymyxin B (PMB). The inflammatory activity of the LPS-PMB complex in blood was examined in vitro in freshly drawn blood samples. Plasma protein binding of PMB was determined by ultracentrifugation using membranes with different molecular cut-offs, and PMB clearance during dialysis was calculated after in vitro experiments using the AV1000S filter. The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion. According to in vitro measurements, the appropriate plasma level of PMB for LPS inactivation is between 100 and 200 ng/ml. Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model. Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure. PMID- 26993090 TI - Cost-effectiveness of Continuous Positive Airway Pressure Treatment in Moderate Severe Obstructive Sleep Apnea Syndrome. AB - INTRODUCTION: The socioeconomic impact of obstructive sleep apnea-hypopnea syndrome (OSAHS) is considerable. The aim of this study was to evaluate the cost effectiveness of treating OSAHS with continuous positive airway pressure (CPAP) and the impact of CPAP compliance. METHODS: This was a retrospective, case crossover study of 373 patients with OSAHS receiving CPAP. We compared changes in costs, Epworth score and health-related quality of life (EQ-5D questionnaires) between the year before treatment and the year after treatment. The incremental cost-effectiveness ratio (ICER) for the first year of treatment was estimated, and projections were made for the second year, using different effectiveness and cost scenarios. RESULTS: The visual analog scale score for the EQ-5D questionnaire increased by 5 points and the Epworth score fell by 10 points during the year of CPAP treatment. Mean gain in quality-adjusted life years (QALY) was 0.05 per patient per year (P<.001): 0.07 among compliers and -0.04 among non-compliers. ICER was ?51,147/QALY during the first year of CPAP treatment and ?1,544/QALY during the second year. CONCLUSION: CPAP treatment in patients with moderate-severe OSAHS improves the quality of life of compliant patients, and is cost-effective as of the second year. PMID- 26993096 TI - Inflammatory bowel disease as a paradoxical effect of anti-TNF alpha therapy. AB - Anti-TNF-alpha therapies are used in the treatment of different inflammatory conditions, such as inflammatory bowel disease (IBD). However, paradoxical effects may occur during treatment. In other words, these drugs can induce or unmask diseases similar to those they were intended to treat. Etanercept is the main anti-TNF-alpha agent associated with the development of paradoxical IBD; this drug, moreover, has no proven usefulness in the treatment of the disease. This association, which is not coincidental and meets the criteria for a temporal causal association, is infrequent and is seen particularly in patients with spondyloarthritis. Restarting treatment with etanercept may induce new intestinal symptoms. There are no endoscopic, histopathologic or clinical differences between primary and secondary IBD, and both are diagnosed in the same way. The most frequent presentation is Crohn disease. When a paradoxical event occurs, etanercept is usually replaced with infliximab, which has not been associated with disease recurrence. PMID- 26993089 TI - R-spondin 1 and noggin facilitate expansion of resident stem cells from non damaged gallbladders. AB - Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine, and colon. Expansion of these cells requires activation of the receptor Lgr5 by its ligand R-spondin 1 and is likely facilitated by the fact that in healthy adults the stem cells in these organs are highly proliferative. In many other adult organs, such as the liver, proliferating cells are normally not abundant in adulthood. However, upon injury, the liver has a strong regenerative potential that is accompanied by the emergence of Lgr5-positive stem cells; these cells can be isolated and expanded in vitro as organoids. In an effort to isolate stem cells from non-regenerating mouse livers, we discovered that healthy gallbladders are a rich source of stem/progenitor cells that can be propagated in culture as organoids for more than a year. Growth of these organoids was stimulated by R-spondin 1 and noggin, whereas in the absence of these growth factors, the organoids differentiated partially toward the hepatocyte fate. When transplanted under the liver capsule, gallbladder-derived organoids maintained their architecture for 2 weeks. Furthermore, single cells prepared from dissociated organoids and injected into the mesenteric vein populated the liver parenchyma of carbon tetrachloride treated mice. Human gallbladders were also a source of organoid-forming stem cells. Thus, under specific growth conditions, stem cells can be isolated from healthy gallbladders, expanded almost indefinitely in vitro, and induced to differentiate toward the hepatocyte lineage. PMID- 26993097 TI - Schistosomiasis knowledge, attitude, practices, and associated factors among primary school children in the Siphofaneni area in the Lowveld of Swaziland. AB - BACKGROUND: Schistosomiasis, a worldwide concern, has received attention in Swaziland through control programs such as deworming programs, education programs, and school health programs; however, these programs neglect the importance of monitoring and evaluation strategies such as assessing children's knowledge, attitudes and practices (KAPs) and the prevalence of the disease. Children are a high-risk group because of their water contact practices, and need to be informed about schistosomiasis to influence their attitudes and practices. Social and cultural factors are involved in schistosomiasis control because they instill myths and misconceptions about the disease. As a result, children in the community may be comfortable with bad practices. This study aimed to assess the KAPs of schoolchildren on schistosomiasis, and to identify practices that support or hinder the progress of schistosomiasis control. METHODS: In 2014, a descriptive quantitative cross-sectional survey was conducted through questionnaires among Siphofaneni primary schools, an area hit by schistosomiasis in the Lowveld of Swaziland. A logistic regression model was applied to analyze the data. RESULTS: Moderate knowledge, good attitudes, and fairly good practices were observed in the children. However, practices of certain children were risky and they still had some misconceptions. Knowledge was correlated with practice and with predictors of good and bad practices such as male sex, always urinating in water, and always using river water for domestic practices. CONCLUSION: This study suggests that empowering children with knowledge and attempting to modify their water contact, and improved human waste disposal practices are necessary for schistosomiasis control. PMID- 26993099 TI - Erratum to: Promoter-like epigenetic signatures in exons displaying cell type specific splicing. PMID- 26993098 TI - Bottom-up GGM algorithm for constructing multilayered hierarchical gene regulatory networks that govern biological pathways or processes. AB - BACKGROUND: Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways. RESULTS: A bottom-up graphic Gaussian model (GGM) algorithm was developed for constructing ML-hGRN operating above a biological pathway using small- to medium-sized microarray or RNA-seq data sets. The algorithm first placed genes of a pathway at the bottom layer and began to construct a ML-hGRN by evaluating all combined triple genes: two pathway genes and one regulatory gene. The algorithm retained all triple genes where a regulatory gene significantly interfered two paired pathway genes. The regulatory genes with highest interference frequency were kept as the second layer and the number kept is based on an optimization function. Thereafter, the algorithm was used recursively to build a ML-hGRN in layer-by-layer fashion until the defined number of layers was obtained or terminated automatically. CONCLUSIONS: We validated the algorithm and demonstrated its high efficiency in constructing ML hGRNs governing biological pathways. The algorithm is instrumental for biologists to learn the hierarchical regulators associated with a given biological pathway from even small-sized microarray or RNA-seq data sets. PMID- 26993094 TI - From Bench to Bedside: New Approaches to Therapeutic Discovery for Heart Failure. AB - Heart failure is a significant global health problem, which is becoming worse as the population ages, and remains one of the biggest burdens on our economy. Despite significant advances in cardiovascular medicine, management and surgery, mortality rates remain high, with almost half of patients with heart failure dying within five years of diagnosis. As a multifactorial clinical syndrome, heart failure still represents an epidemic threat, highlighting the need for deeper insights into disease mechanisms and the development of innovative therapeutic strategies for both treatment and prevention. In this review, we discuss conventional heart failure therapies and highlight new pharmacological agents targeting pathophysiological features of the failing heart, for example, non-coding RNAs, angiotensin receptor-neprilysin inhibitors, cardiac myosin activators, BGP-15 and molecules targeting GRK2 including M119, gallein and paroxetine. Finally, we address the disparity between phase II and phase III clinical trials that prevent the translation of emerging HF therapies into new and approved therapies. PMID- 26993101 TI - Activation of AMPK inhibits PDGF-induced pulmonary arterial smooth muscle cells proliferation and its potential mechanisms. AB - The aims of the present study were to examine signaling mechanisms for PDGF induced pulmonary arterial smooth muscle cells (PASMC) proliferation and to determine the effect of AMPK activation on PDGF-induced PASMC proliferation and its underlying mechanisms. PDGF activated PI3K/Akt/mTOR signaling pathway, and this in turn up-regulated Skp2 and consequently reduced p27 leading to PASMC proliferation. Prior incubation of PASMC with metformin induced a dramatic AMPK activation and significantly blocked PDGF-induced cell proliferation. PASMC lacking AMPKalpha2 were resistant to the inhibitory effect of metformin on PDGF induced cell proliferation. Metformin did not affect Akt activation but blocked mTOR phosphorylation in response to PDGF; these were accompanied by the reversion of Skp2 up-regulation and p27 reduction. Our study suggests that the activation of AMPK negatively regulates mTOR activity to suppress PASMC proliferation and therefore has a potential value in the prevention and treatment of pulmonary hypertension by negatively modulating pulmonary vascular remodeling. PMID- 26993100 TI - Apoptosis-induced ectodomain shedding of hypoxia-regulated carbonic anhydrase IX from tumor cells: a double-edged response to chemotherapy. AB - BACKGROUND: Carbonic anhydrase IX (CA IX) is a tumor-associated, highly active, transmembrane carbonic anhydrase isoform regulated by hypoxia and implicated in pH control and adhesion-migration-invasion. CA IX ectodomain (ECD) is shed from the tumor cell surface to serum/plasma of patients, where it can signify cancer prognosis. We previously showed that the CA IX ECD release is mediated by disintegrin and metalloproteinase ADAM17. Here we investigated the CA IX ECD shedding in tumor cells undergoing apoptosis in response to cytotoxic drugs, including cycloheximide and doxorubicin. METHODS: Presence of cell surface CA IX was correlated to the extent of apoptosis by flow cytometry in cell lines with natural or ectopic CA IX expression. CA IX ECD level was assessed by ELISA using CA IX-specific monoclonal antibodies. Effect of recombinant CA IX ECD on the activation of molecular pathways was evaluated using the cell-based dual luciferase reporter assay. RESULTS: We found a significantly lower occurrence of apoptosis in the CA IX-positive cell subpopulation than in the CA IX-negative one. We also demonstrated that the cell-surface CA IX level dropped during the death progress due to an increased ECD shedding, which required a functional ADAM17. Inhibitors of metalloproteinases reduced CA IX ECD shedding, but not apoptosis. The CA IX ECD release induced by cytotoxic drugs was connected to elevated expression of CA IX in the surviving fraction of cells. Moreover, an externally added recombinant CA IX ECD activated a pathway driven by the Nanog transcription factor implicated in epithelial-mesenchymal transition and stemness. CONCLUSIONS: These findings imply that the increased level of the circulating CA IX ECD might be useful as an indicator of an effective antitumor chemotherapy. Conversely, elevated CA IX ECD might generate unwanted effects through autocrine/paracrine signaling potentially contributing to resistance and tumor progression. PMID- 26993103 TI - Robust adaptive relative position and attitude control for spacecraft autonomous proximity. AB - This paper provides new results of the dynamical modeling and controller designing for autonomous close proximity phase during rendezvous and docking in the presence of kinematic couplings and model uncertainties. A globally defined relative motion mechanical model for close proximity operations is introduced firstly. Then, in spite of the kinematic couplings and thrust misalignment between relative rotation and relative translation, robust adaptive relative position and relative attitude controllers are designed successively. Finally, stability of the overall system is proved that the relative position and relative attitude are uniformly ultimately bounded, and the size of the ultimate bound can be regulated small enough by control system parameters. Performance of the controlled overall system is demonstrated via a representative numerical example. PMID- 26993102 TI - Serelaxin (recombinant human relaxin-2) prevents high glucose-induced endothelial dysfunction by ameliorating prostacyclin production in the mouse aorta. AB - Diabetes-induced endothelial dysfunction is a critical initiating factor in the development of cardiovascular complications. Treatment with relaxin improves tumour necrosis factor alpha-induced endothelial dysfunction by enhancing endothelial nitric oxide synthase (eNOS) activity and restoring superoxide dismutase 1 protein in rat aortic rings ex vivo. It is, therefore, possible that relaxin treatment could alleviate endothelial dysfunction in diabetes. This study aimed to test the hypothesis that serelaxin (recombinant human relaxin-2) prevents high glucose-induced vascular dysfunction in the mouse aorta. Abdominal aortae were isolated from C57BL/6 male mice and incubated in M199 media for 3days with either normal glucose (5.5mM) or high glucose (30mM), and co-incubated with placebo (20mM sodium acetate) or 10nM serelaxin at 37 degrees C in 5% CO2. Vascular function was analysed using wire-myography. High glucose significantly reduced the sensitivity to the endothelium-dependent agonist, acetylcholine (ACh) (pEC50; normal glucose=7.66+/-0.10 vs high glucose=7.29+/-0.10, n=11-12, P<0.05) and the contraction induced by NOS inhibitor, L-NAME (200MUM) (normal glucose=59.9+/-8.3% vs high glucose=38.7+/-4.3%, n=6, P<0.05), but had no effect on the endothelium-independent agonist, sodium nitroprusside (SNP)-mediated relaxation. Treatment with serelaxin restored endothelial function (pEC50; 7.83+/ 0.11, n=11) but not NO availability. The presence of the cyclooxygenase (COX) inhibitor, indomethacin (1MUM) (pEC50; control=7.29+/-0.10 vs indo=7.74+/-0.18, n=6-12, P<0.05) and a superoxide dismutase mimetic, tempol (10MUM) (pEC50; control=7.29+/-0.10 vs tempol=7.82+/-0.05, n=6-12, P<0.01) significantly improved sensitivity to ACh in high glucose treated aortae, but had no effect in serelaxin treated aortae. This suggests that high glucose incubation alters the superoxide and COX-sensitive pathway, which was normalized by co-incubation with serelaxin. Neither high glucose incubation nor serelaxin treatment had an effect on cyclooxygenase 1 and 2 (Ptgs1, Ptgs2), prostacyclin synthase (PTGIS) and receptor (Ptgir) as well as thromboxane A2 receptor (Tbxa2r) mRNA expression. Importantly, production of prostacyclin was significantly (P<0.05) attenuated in high glucose treated aortae, which was prevented by serelaxin treatment. Our data show that serelaxin treatment for 3 days restores high glucose-induced endothelial dysfunction by ameliorating vasodilator prostacyclin production and possibly through the reduction of superoxide in the mouse aorta. PMID- 26993104 TI - Root contact with maxillomandibular fixation screws in orthognathic surgery: incidence and consequences. AB - The use of maxillomandibular fixation (MMF) screws in orthognathic surgery has become common in recent years. The risk of injury to adjacent roots with their placement in this population has not been studied extensively. The aim of this study was to review the incidence and consequences of root contact/injury in patients undergoing orthognathic surgery. A retrospective analysis of the treatment and radiographic records of patients who underwent orthognathic surgery between January 2013 and September 2014 at a university in Kentucky, USA was performed. The mean number of screws used was correlated to the mean number of roots affected using Spearman's test, set to a level of significance of 5%. Of 125 patients who underwent orthognathic surgery, 15 (12%) had evidence of root contact. Subsequent radiographs showed resolution of the bone defects. There was no clinical evidence of pulpal necrosis or pain during follow-up. The average number of screws used was 3.14+/-0.35 per patient, with an average of 0.17+/-0.52 root contacts per patient. There was no correlation between the number of screws used and the number of roots injured (P=0.279). Based on these results, MMF screws can safely be used to establish interim fixation during orthognathic surgery. Caution should be taken during placement to avoid direct injury to the roots of teeth. PMID- 26993105 TI - Can calcitonin nasal spray reduce the risk of recurrence of central giant cell granuloma of the jaws? A double-blind clinical trial. AB - Recurrence is a major problem following the treatment of aggressive central giant cell granuloma (CGCG). The aim of this study was to compare the frequency of recurrence between patients who received calcitonin nasal spray after curettage of CGCGs and those who did not. A double-blind clinical trial was designed. Patients were allocated to one of two groups: those in the calcitonin group underwent curettage and received calcitonin salmon nasal spray 200IU/day once a day for 3 months after surgery; those in the control group underwent curettage of CGCGs and received a placebo once a day for 3 months after surgery. All patients were followed for 5 years after surgery. Twenty-four patients were treated in the two groups. There was no difference in age, sex, tumour size, or tumour location between the two groups (P>0.05). Eight of the 24 patients (33.3%) had recurrences during the follow-up period: one in the calcitonin group (9.1%) and seven in the control group (53.8%). Analysis of the data demonstrated a significant difference between the two study groups (P=0.033). It appears that calcitonin nasal spray may reduce the frequency of recurrence in aggressive CGCGs in the mandible and maxilla. PMID- 26993106 TI - The anterior maxilla as a potential source of bone grafts: a morphometric cone beam computed tomography analysis of different anatomical areas. AB - The aim of this research was to use cone beam computed tomography (CBCT) to analyze the volume, density, and morphology of the bone available in the anterior region of the maxilla, in order to investigate its potential as a source of bone grafts. Three independent zones were evaluated: the palatine process of the maxilla (PPM), anterior nasal spine (ANS), and subnasal bone (SN). The latter was analyzed bilaterally (SNR, SNL). One hundred CBCT scans were evaluated. The morphometric analysis comprised volumetric and subsequent automatic density calculations, as well as linear measurements. Potential correlations among these parameters, including demographic characteristics, were investigated. The study comprised 52 women and 48 men (mean age 49.6+/-14.5 years). The calculated bone volume averaged 2.41+/-0.72cm(3) for PPM, 0.46+/-0.16cm(3) for ANS, 0.58+/ 0.2cm(3) for SNR, and 0.57+/-0.21cm(3) for SNL. The anterior region of the maxilla can provide a considerable amount of bone volume from different anatomical zones and should be regarded as a potential donor site for the regeneration of maxillary atrophic bones. Further investigation is required before these findings can be applied in the routine clinical setting. PMID- 26993107 TI - Case series of recalcitrant livedoid vasculopathy treated with rivaroxaban. PMID- 26993108 TI - Distribution and predictors of emergency department charges: the case of a tertiary hospital in Lebanon. AB - BACKGROUND: As health care costs continue to increase worldwide, health care systems, and more specifically hospitals are facing continuous pressure to operate more efficiently. One service within the hospital sector whose cost structure has been modestly investigated is the Emergency Department (ED). The study aims to report on the distribution of ED resource use, as expressed in charges, and to determine predictors of/contributors to total ED charges at a major tertiary hospital in Lebanon. METHODS: The study used data extracted from the ED discharge database for visits between July 31, 2012 and July 31, 2014. Patient visit bills were reported under six major categories: solutions, pharmacy, laboratory, physicians, facility, and radiology. Characteristics of ED visits were summarized according to patient gender, age, acuity score, and disposition. Univariate and multivariate analyses were conducted with total charges as the dependent variable. RESULTS: Findings revealed that the professional fee (40.9 %) followed by facility fee (26.1 %) accounted for the majority of the ED charges. While greater than 80 % of visit charges went to physician and facility fee for low acuity cases, these contributed to only 52 and 54 % of the high acuity presentations where ancillary services and solutions' contribution to the total charges increased. The total charges for males were $14 higher than females; age was a predictor of higher charges with total charges of patients greater than 60 years of age being around $113 higher than ages 0-18 after controlling for all other variables. CONCLUSION: Understanding the components and determinants of ED charges is essential to developing cost containment interventions. Institutional modeling of charging patterns can be used to offer price estimates to ED patients who request this information and ultimately help create market competition to drive down costs. PMID- 26993109 TI - Technique to avoid left ventricular outflow tract obstruction. AB - Preserving the subvalvular mitral valve apparatus during mitral valve replacement is extremely important to minimize progressive postoperative left ventricular remodeling and dysfunction. We describe a simple and reproducible surgical technique that prevents the complications that can occur after total mitral anterior leaflet preservation. PMID- 26993111 TI - Factors influencing infection in 10 years of battlefield open tibia fractures. AB - The aim of this study was to characterise severe open tibial shaft fractures sustained by the UK military personnel over 10 years of combat in Iraq and Afghanistan. The UK military Joint Theatre Trauma Registry was searched for all such injuries, and clinical records were reviewed for all patients. One hundred Gustilo-Anderson III tibia fractures in 89 patients were identified in the 10 year study period; the majority sustained injuries through explosive weapons (63, 68 %) with the remainder being injured from gunshot wounds. Three fractures were not followed up for 12 months and were therefore excluded. Twenty-two (23 %) of the remaining 97 tibial fractures were complicated by infection, with S. aureus being the causative agent in 13/22 infected fractures (59 %). Neither injury severity, mechanism, the use of an external fixator, the need for vascularised tissue transfer nor smoking status was associated with subsequent infection. Bone loss was significantly associated with subsequent infection (p < 0.0001, Fisher's exact test). This study presents 10 years of open tibial fractures sustained in Iraq and Afghanistan. Most infection in combat open tibia fractures is caused by familiar organisms, i.e. S. aureus. While the overall severity of a casualty's injuries was not associated with infection, the degree of bone loss from the fracture was. PMID- 26993112 TI - Erratum to: External fixation reconstruction of the residual problems of benign bone tumours. PMID- 26993113 TI - Quality of Life in Community-Dwelling Chinese American Patients with Cancer Pain. AB - Although pain can be a powerful influence on health-related quality of life (HRQL) in cancer populations, culturally-based beliefs and behaviors may directly impact HQRL or modify the association between pain and HQRL. Studies of well defined ethnic groups may clarify these relationships and inform culturally competent clinical practices intended to reduce illness burden. We evaluated HRQL in 121 non-English-speaking Chinese immigrants with cancer pain using the Functional Assessment of Cancer Therapy-General (FACT-G) scale. Overall, 91.2 % were born in China and 86.0 % were Cantonese-speaking; 50.8 % had no formal education (mean age = 63.2 years; 68.6 % women). Although the mean FACT-G score did not differ from U.S. population norms, most subscale scores for Chinese immigrants were lower and the score for social/family well-being was higher (all p < 0.05). Higher educational level, caregiver presence, lower psychological distress, lower pain intensity and interference, and lower symptom distress were associated with better HRQL (all p < 0.05). These findings confirm the importance of diverse influences on HQRL in ethnic Chinese cancer patients with chronic pain and suggest that this group may be distinguished from the majority population by the extent to which social/family well-being is preserved. Future studies in the growing population of Chinese Americans with cancer are needed to evaluate various aspects of social/family well-being and determine whether they modify the association between pain and HRQL. PMID- 26993114 TI - Syphilis Among U.S.-Bound Refugees, 2009-2013. AB - U.S. immigration regulations require clinical and serologic screening for syphilis for all U.S.-bound refugees 15 years of age and older. We reviewed syphilis screening results for all U.S.-bound refugees from January 1, 2009 through December 31, 2013. We calculated age-adjusted prevalence by region and nationality and assessed factors associated with syphilis seropositivity using multivariable log binomial regression models. Among 233,446 refugees, we identified 874 syphilis cases (373 cases per 100,000 refugees). The highest overall age-adjusted prevalence rates of syphilis seropositivity were observed among refugees from Africa (1340 cases per 100,000), followed by East Asia and the Pacific (397 cases per 100,000). In most regions, male sex, increasing age, and living in non-refugee camp settings were associated with syphilis seropositivity. Future analysis of test results, stage of infection, and treatment delivery overseas is warranted in order to determine the extent of transmission risk and benefits of the screening program. PMID- 26993115 TI - Utilitarian and Recreational Walking Among Spanish- and English-Speaking Latino Adults in Micropolitan US Towns. AB - BACKGROUND: Walking among Latinos in US Micropolitan towns may vary by language spoken. METHODS: In 2011-2012, we collected telephone survey and built environment (BE) data from adults in six towns located within micropolitan counties from two states with sizable Latino populations. We performed mixed effects logistic regression modeling to examine relationships between ethnicity language group [Spanish-speaking Latinos (SSLs); English-speaking Latinos (ESLs); and English-speaking non-Latinos (ENLs)] and utilitarian walking and recreational walking, accounting for socio-demographic, lifestyle and BE characteristics. RESULTS: Low-income SSLs reported higher amounts of utilitarian walking than ENLs (p = 0.007), but utilitarian walking in this group decreased as income increased. SSLs reported lower amounts of recreational walking than ENLs (p = 0.004). ESL ENL differences were not significant. We identified no statistically significant interactions between ethnicity-language group and BE characteristics. DISCUSSION: Approaches to increase walking in micropolitan towns with sizable SSL populations may need to account for this group's differences in walking behaviors. PMID- 26993116 TI - Retinal degeneration in primary-progressive multiple sclerosis: A role for cortical lesions? AB - BACKGROUND: Retinal atrophy in multiple sclerosis (MS) is secondary to optic nerve focal inflammation and to injury of the posterior visual pathway. OBJECTIVES: To investigate the contribution of cortical lesions (CLs) to retinal pathology in primary-progressive multiple sclerosis (PPMS). METHODS: We performed a cross-sectional evaluation of 25 patients and 20 controls, relating magnetic resonance imaging (MRI) metrics of visual pathway integrity with parameters derived from spectral-domain optical coherence tomography (peripapillary retinal nerve fiber layer (RNFL) thickness, ganglion cell + inner plexiform layer (GCIPL) thickness, and macular volume (MV)). RESULTS: Mean RNFL, GCIPL thickness, and MV were significantly reduced in patients compared to controls. MV and GCIPL thickness were significantly correlated with visual acuity. RNFL thinning was associated with thalamus and visual cortex volume (respectively, p = 0.01 and p < 0.05). In addition to thalamic volume, GCIPL thinning was associated with CLs and intracortical lesion number and volume, leucocortical lesion volume (all p ? 0.05) while MV decrease was associated with CLs volume ( p = 0.05) and intracortical lesion number and volume ( p < 0.05). CONCLUSION: Our results suggest that RNFL thinning and GCIPL thinning/MV decrease may be explained by alternative mechanisms including retrograde trans-synaptic degeneration and/or a common pathophysiologic process affecting both the brain with CLs and the retina with neuronal loss. PMID- 26993117 TI - D313Y mutation in the differential diagnosis of white matter lesions: Experiences from a multiple sclerosis outpatient clinic. AB - White matter lesions (WML) in younger patients might be due to a variety of neurological disorders. Fabry disease (FD), an x-linked inherited lysosomal storage disorder, happens to be misdiagnosed as multiple sclerosis (MS). In two middle-aged female patients, presenting bilateral WML, diagnosis of MS turned out to be doubtful. Human genetic analysis presented the Fabry mutation D313Y, in which clinical impact is still unclear. Disease manifestations outside the central nervous system were not detected. Our findings support the suspicion that Fabry mutation D313Y may be involved in neural damage resulting in WML. PMID- 26993118 TI - Lymphomatoid papulosis and fingolimod-A new connection? PMID- 26993119 TI - Cardiac stunning as first manifestation of multiple sclerosis: A case report reminding us not to overlook cardiovascular autonomic dysfunction in multiple sclerosis. AB - Autonomic dysfunction is common but frequently overlooked in multiple sclerosis (MS) patients. The case of a Tako-Tsubo cardiomyopathy on which this commentary is based shows that centrally triggered autonomic dysfunction may be the first life-threatening manifestation of MS. PMID- 26993120 TI - An uncommon first manifestation of multiple sclerosis: Tako-Tsubo cardiomyopathy. AB - BACKGROUND: Clinically isolated syndromes affecting the brainstem may present with rare manifestations such as neurogenic pulmonary oedema (NPO). OBJECTIVES: We present the case of a 23 year-old man with NPO caused by Tako-Tsubo cardiomyopathy (TTC) as a first manifestation of multiple sclerosis (MS). METHODS AND RESULTS: A brain magnetic resonance imaging scan at admission showed multiple supra and infratentorial white matter inflammatory demyelinating lesions. This examination was repeated 2 and 4 weeks after symptoms onset and active lesions showing contrast uptake were identified, two of them involving the pons and the medulla oblongata, probably affecting the solitary tract nucleus. Cerebrospinal fluid oligoclonal bands were detected. The patient was treated with a 3-day course of 1g intravenous methylprednisolone presenting a significant and progressive improvement. The proposed underlying physiopathology is an excessive secretion of catecholamines resulting in myocardial stunning and ventricular failure. Two months later he developed optic neuritis and disease-modifying treatment was initiated. CONCLUSIONS: Clinicians should consider a possible neurological origin of TTC, and according to the clinical characteristics of the patient, MS may be suspected. PMID- 26993121 TI - [Resectability of pancreatic cancer: New criteria]. AB - BACKGROUND: Pancreatic cancer is notoriously one of the most aggressive cancers and still has a poor prognosis. Surgical resection is the only chance for a curative therapy approach, with which at least a 5-year survival can be achieved for 25% of patients. Recent advances in surgical techniques have led to a change in the criteria for resectability. OBJECTIVE: This review summarizes the currently available evidence on the criteria for resectability of pancreatic cancer and discusses the treatment options. MATERIAL AND METHODS: The study was based on a selective literature search and a summary of the latest data on criteria for resectability is given. RESULTS: Patients with pancreatic cancer must be differentiated into those with primarily resectable disease, borderline resectable disease, locally advanced (primarily unresectable) and metastatic disease. While infiltration into the major surrounding venous vessels (e.g. superior mesenteric vein, portal vein and confluence of splenic vein) used to be a criterion for unresectable disease, these tumors can nowadays be safely resected in specialized centers. Tumor infiltration into adjacent arteries (e.g. hepatic artery, superior mesenteric artery and celiac artery) remains a clinical problem and surgical resection is often technically possible but associated with an increased morbidity and mortality and therefore not generally recommended. Borderline resectable tumors represent a special group for which neoadjuvant treatment concepts are increasingly being implemented. Radiological therapy response evaluation is challenging after neoadjuvant therapy as it is not usually associated with a radiologically detectable reduction in tumor volume. CONCLUSION: Pancreatic resections can nowadays be more radically performed due to advances in surgical techniques. This has led to a change in the criteria for resectability, especially concerning venous tumor infiltration. PMID- 26993122 TI - Association between ALDH1L1 gene polymorphism and neural tube defects in the Chinese Han population. AB - We investigated single-nucleotide polymorphisms (SNPs) in the aldehyde dehydrogenase family1 L1 gene (ALDH1L1) and their association with neural tube defects (NTDs) in the Chinese population. A total of 271 NTDs cases and 192 healthy controls were used in this study. A total of 112 selected SNPs in the ALDH1L1 gene were analyzed using the next-generation sequencing method. Statistical analysis was carried out to investigate the correlation between SNPs and patient susceptibility to NTDs. Statistical analysis revealed a significant correlation between the SNP sites rs4646733, rs2305225, and rs2276731 in the ALDH1L1 gene and NTDs. The TT genotype and T allele of rs4646733 in ALDH1L1 were associated with a significantly increased incidence of NTDs [odds ratio (OR) = 2.16, 95 % confidence interval (CI) 1.199-3.896 for genotype; and OR = 1.46, 95 % CI 1.092-1.971 for allele]. The AA genotype and A allele of rs2305225 in ALDH1L1 were associated with a significantly increased incidence of NTDs (OR = 2.03, 95 % CI 1.202-3.646 for genotype, and OR = 1.44, 95 % CI 1.096-1.905 for allele). The CT genotype and C allele of rs2276731 in ALDH1L1 significantly were associated with an increased incidence of NTDs (OR = 1.67, 95 % CI 1.129-2.491 with genotype, and OR = 1.32, 95 % CI 0.956-1.816 with allele).The polymorphic loci rs4646733, rs2305225, and rs2276731 in the ALDH1L1 gene maybe potential risk factors for NTDs in the Chinese population. PMID- 26993123 TI - Viral seroprevalence in northern pig-tailed macaques (Macaca leonina) derived from Ho Chi Minh City, Vietnam. AB - Non-human primates are natural virus reservoirs, whether wild or domestic. In this study, we determined the seroprevalence of common viruses by ELISA in a northern pig-tailed macaque (Macaca leonina) colony derived from Ho Chi Minh City, Vietnam. A total of 20 types of virus which are commonly selected as target microorganisms for specific-pathogen-free colonies, or which have zoonotic potential were included in this study. The results showed only 2 in 90 northern pig-tailed macaques were seronegative for all the detected viruses, and at least 16 out of the total 20 types of virus tested were prevalent in this colony, so these macaques were commonly infected by various viruses. These macaques should be carefully assessed for viral seroprevalence in order to prevent zoonotic diseases from being transferred to human beings. PMID- 26993124 TI - Dietary patterns and breast cancer risk in a prospective Japanese study. AB - BACKGROUND: The association between dietary patterns and breast cancer has been inconsistent. METHODS: This study examined associations between dietary patterns and risk of developing breast cancer among 23,172 women from the Japan Collaborative Cohort Study, including 119 incidences of breast cancer diagnosed during a median 16.9-year follow-up period. Factor analysis was conducted to obtain dietary patterns, and Cox proportional models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) for breast cancer morbidity. RESULTS: Three dietary patterns were identified: ''vegetable pattern'' (vegetables, potatoes, seaweed, tofu, fruits, fresh fish, eggs, and miso soup); ''animal food pattern'' (meat, deep-fried foods, fried vegetables, fish paste and salt-preserved fish); and "dairy product pattern'' (milk, dairy products, fruits, coffee and tea). After adjusting for potential confounders, the vegetable and dairy product patterns were not significantly associated with risk of breast cancer. However, the animal food pattern was significantly associated with a decreased risk of breast cancer morbidity among premenopausal women by HR 0.47 for the 2nd tertile (95 % CI 0.22-1.00) and HR 0.42 for the 3rd tertile (95 % CI 0.18-0.93), compared with the bottom tertile (p for trend 0.04). CONCLUSION: We found no significant association between the vegetable and dairy product dietary patterns and breast cancer risk; however, an animal product diet may reduce risk of breast cancer among premenopausal Japanese women. PMID- 26993125 TI - Structure, function and disease relevance of Omega-class glutathione transferases. AB - The Omega-class cytosolic glutathione transferases (GSTs) have distinct structural and functional attributes that allow them to perform novel roles unrelated to the functions of other GSTs. Mammalian GSTO1-1 has been found to play a previously unappreciated role in the glutathionylation cycle that is emerging as significant mechanism regulating protein function. GSTO1-1-catalyzed glutathionylation or deglutathionylation of a key signaling protein may explain the requirement for catalytically active GSTO1-1 in LPS-stimulated pro inflammatory signaling through the TLR4 receptor. The observation that ML175 a specific GSTO1-1 inhibitor can block LPS-stimulated inflammatory signaling has opened a new avenue for the development of novel anti-inflammatory drugs that could be useful in the treatment of toxic shock and other inflammatory disorders. The role of GSTO2-2 remains unclear. As a dehydroascorbate reductase, it could contribute to the maintenance of cellular redox balance and it is interesting to note that the GSTO2 N142D polymorphism has been associated with multiple diseases including Alzheimer's disease, Parkinson's disease, familial amyotrophic lateral sclerosis, chronic obstructive pulmonary disease, age-related cataract and breast cancer. PMID- 26993126 TI - Semantic information mediates visual attention during spoken word recognition in Chinese: Evidence from the printed-word version of the visual-world paradigm. AB - In the present study, we investigated whether the activation of semantic information during spoken word recognition can mediate visual attention's deployment to printed Chinese words. We used a visual-world paradigm with printed words, in which participants listened to a spoken target word embedded in a neutral spoken sentence while looking at a visual display of printed words. We examined whether a semantic competitor effect could be observed in the printed word version of the visual-world paradigm. In Experiment 1, the relationship between the spoken target words and the printed words was manipulated so that they were semantically related (a semantic competitor), phonologically related (a phonological competitor), or unrelated (distractors). We found that the probability of fixations on semantic competitors was significantly higher than that of fixations on the distractors. In Experiment 2, the orthographic similarity between the spoken target words and their semantic competitors was manipulated to further examine whether the semantic competitor effect was modulated by orthographic similarity. We found significant semantic competitor effects regardless of orthographic similarity. Our study not only reveals that semantic information can affect visual attention, it also provides important new insights into the methodology employed to investigate the semantic processing of spoken words during spoken word recognition using the printed-word version of the visual-world paradigm. PMID- 26993127 TI - Childhood Vaccine Exemption Policy: The Case for a Less Restrictive Alternative. PMID- 26993128 TI - A Rare Case Report of Immobility-Induced Hypercalcemia in an Infant. AB - Immobility-induced hypercalcemia is a rare cause of hypercalcemia in children, and to our knowledge it has never been reported in an infant. Infants and children are in a state of high bone turnover. Therefore, they are prone to the imbalance of osteoblastic and osteoclastic activity that occurs with prolonged immobilization, leading to hypercalcemia. Here we present the case of an infant with hypercalcemia who presented with fatigue, irritability, and failure to thrive after prolonged immobilization. Therapeutic interventions were conservative and included hydration and increased mobility leading to complete resolution. This case highlights the importance of including this rare entity in a differential diagnosis of hypercalcemia as well as screening postsurgical patients with prolonged immobility for hypercalcemia. PMID- 26993129 TI - Childhood Vaccine Exemptions: A Broader Perspective Is Required. PMID- 26993130 TI - Erratum to: PI3K/mTOR inhibition can impair tumor invasion and metastasis in vivo despite a lack of antiproliferative action in vitro: implications for targeted therapy. AB - Erratum to: Breast Cancer Res Treat (2013),138:369-381,DOI 10.1007/s10549-012 2389-6. In the original publication of the article, the Fig. 4c and d were published erroneously. The revised Fig. 4 is given in this erratum. PMID- 26993131 TI - A non-randomized dose-escalation Phase I trial of a protein-based immunotherapeutic for the treatment of breast cancer patients with HER2 overexpressing tumors. AB - This Phase I dose-escalation study (NCT00058526) assessed the safety and immunogenicity of an anti-cancer immunotherapeutic (recombinant HER2 protein (dHER2) combined with the immunostimulant AS15) in patients with early-stage HER2 overexpressing breast cancer (BC). Sixty-one trastuzumab-naive patients with stage II-III HER2-positive BC received the dHER2 immunotherapeutic after surgical resection and adjuvant therapy. They were allocated into four cohorts receiving different doses of dHER2 (20, 100, 500 ug) combined with a fixed AS15 dose. Safety and immunogenicity (dHER2-specific antibody responses) were assessed. After completing the immunization schedule (three or six doses over 14 weeks) and a six-month follow-up, the patients were followed for 5 years for late toxicity, long-term immunogenicity, and clinical status. The immunizations were well tolerated, and increasing doses of dHER2 had no impact on the frequency or severity of adverse events. Few late toxicities were reported, and after 5 years 45/54 patients (83.3 %) were still alive, while 28/45 (62 %) with known disease status were disease free. Regarding the immunogenicity of the compound, a positive association was found between the dHER2 dose, the immunization schedule, and the prevalence of dHER2-specific humoral responses. Among the patients receiving the most intense immunization schedule with the highest dHER2 dose, 6/8 maintained their dHER2-specific antibody response 5 years after immunization. The dHER2 immunotherapeutic had an acceptable safety profile in early HER2-positive BC patients. dHER2-specific antibody responses were induced, with the rate of responders increasing with the dHER2 dose and the number and frequency of immunizations. PMID- 26993132 TI - Specificity of Balance Training in Healthy Individuals: A Systematic Review and Meta-Analysis. AB - BACKGROUND: It has become common practice to incorporate balance tasks into the training program for athletes who want to improve performance and prevent injuries, in rehabilitation programs, and in fall prevention programs for the elderly. However, it is still unclear whether incorporating balance tasks into a training program increases performance only in these specific tasks or if it affects balance in a more general way. OBJECTIVES: The objective of this systematic literature review and meta-analysis was to determine to what extent the training of balance tasks can improve performance in non-trained balance tasks. DATA SOURCES: A systematic literature search was performed in the online databases EMBASE, PubMed, SPORTDiscus and Web of Science. Articles related to balance training and testing in healthy populations published between January 1985 and March 2015 were considered. STUDY ELIGIBILITY CRITERIA: A total of 3093 articles were systematically evaluated. Randomized controlled trials were included that (i) used only balance tasks during the training, (ii) used at least two balance tests before and after training, and (iii) tested performance in the trained balance tasks and at least one non-trained balance task. Six studies with a total of 102 subjects met these criteria and were included into the meta analysis. STUDY APPRAISAL AND SYNTHESIS METHODS: The quality of the studies was evaluated by means of the Physiotherapy Evidence Database (PEDro) scale. A random effect model was used to calculate the between-subject standardized mean differences (SMDbs) in order to quantify the effect of balance training on various kinds of balance measures relative to controls. The tested balance tasks in each study were classified into tasks that had been trained and tasks that had not been trained. For further analyses, the non-trained balance tasks were subdivided into tasks with similar or non-similar body position and similar or non-similar balance perturbation direction compared to the trained task. RESULTS: The effect of balance training on the performance of the trained balance tasks reached an SMDbs of 0.79 [95 % confidence interval (CI) 0.48-1.10], indicating a high effect in favor for the trained task, with no notable heterogeneity (I (2) = 0 %). The SMDbs in non-trained categories reached values between -0.07 (95 % CI 0.53 to 0.38) and 0.18 (95 % CI -0.27 to 0.64), with non-notable to moderate heterogeneity (I (2) = 0-32 %), indicating no effect of the balance training on the respective non-trained balance tasks. LIMITATIONS: With six studies, the number of studies included in this meta-analysis is rather low. It remains unclear how the limited number of studies with considerable methodological diversity affects the outcome of the SMD calculations and thus the general outcome of the meta-analysis. CONCLUSION: In healthy populations, balance training can improve the performance in trained tasks, but may have only minor or no effects on non-trained tasks. Consequently, therapists and coaches should identify exactly those tasks that need improvement, and use these tasks in the training program and as a part of the test battery that evaluates the efficacy of the training program. Generic balance tasks-such as one-leg stance-may have little value as overall balance measures or when assessing the efficacy of specific training interventions. PMID- 26993134 TI - Hand and Eye Dominance in Sport: Are Cricket Batters Taught to Bat Back-to-Front? AB - BACKGROUND: When first learning to bimanually use a tool to hit a target (e.g., when chopping wood or hitting a golf ball), most people assume a stance that is dictated by their dominant hand. By convention, this means that a 'right-handed' or 'left-handed' stance that places the dominant hand closer to the striking end of the tool is adopted in many sports. OBJECTIVE: The aim of this study was to investigate whether the conventional stance used for bimanual hitting provides the best chance of developing expertise in that task. METHODS: Our study included 43 professional (international/first-class) and 93 inexperienced (<5 years' experience) cricket batsmen. We determined their batting stance (plus hand and eye dominance) to compare the proportion of batters who adopted a reversed stance when batting (that is, the opposite stance to that expected based on their handedness). RESULTS: We found that cricket batsmen who adopted a reversed stance had a stunning advantage, with professional batsmen 7.1 times more likely to adopt a reversed stance than inexperienced batsmen, independent of whether they batted right or left handed or the position of their dominant eye. CONCLUSION: Findings imply that batsmen who adopt a conventional stance may inadvertently be batting 'back-to-front' and have a significant disadvantage in the game. Moreover, the results may generalize more widely, bringing into question the way in which other bimanual sporting actions are taught and performed. PMID- 26993133 TI - Towards a Determination of the Physiological Characteristics Distinguishing Successful Mixed Martial Arts Athletes: A Systematic Review of Combat Sport Literature. AB - BACKGROUND: Mixed martial arts (MMA) is a combat sport underpinned by techniques from other combat disciplines, in addition to strategies unique to the sport itself. These sports can be divided into two distinct categories (grappling or striking) based on differing technical demands. Uniquely, MMA combines both methods of combat and therefore appears to be physiologically complex requiring a spectrum of mechanical and metabolic qualities to drive performance. However, little is known about the physiological characteristics that distinguish higher- from lower-level MMA athletes. Such information provides guidance for training interventions, performance testing and talent identification. Furthermore, while MMA incorporates techniques from both grappling and striking sports, it is unknown precisely how these disciplines differ physiologically. Understanding the relationship between higher-level competitors in grappling and striking combat sports can provide further insight into the development of the optimal performance profile of a higher-level MMA athlete. OBJECTIVE: This article aims to analyse the scientific literature on MMA and the primary combat sports underpinning it to determine the physiological adaptations that distinguish superior competitors, with a view to defining the optimal physiological profile for higher-level MMA performance. Furthermore, this article will explore the differences in these capabilities between grappling- and striking-based combat sports in the context of MMA. METHODS: A literature search was undertaken via PubMed, Web of Science, SportDiscus and Google Scholar. The following sports were included for systematic review based on their relevance to MMA: mixed martial arts, boxing, Brazilian jiu-jitsu, judo, karate, kickboxing, Muay Thai and wrestling. The inclusion criteria allowed studies that compared athletes of differing competition levels in the same sport using a physiological performance measure. Only male, adult (aged 17-40 years), able-bodied competitors were included. The search history spanned from the earliest record until September 2015. RESULTS: Of the eight combat sports searched for, five were represented across 23 studies. Sixteen investigations described maximal strength or neuromuscular power variables, while 19 articles reported anaerobic or aerobic measures. The results indicate that a number of strength, neuromuscular power and anaerobic variables distinguished higher- from lower-level combat sport athletes. However, these differences were less clear when groups were stratified within, rather than between competition grades. Greater aerobic power was generally not present amongst superior combat sport competitors. CONCLUSION: There appear to be differing physiological profiles between more successful grappling and striking combat sport athletes. This is represented by high-force demands of grappling sports causing an upwards shift of the entire force-velocity relationship driven by an increase in maximal strength. In comparison, smaller increases in maximal force production with more notable enhancements in lighter load, higher velocity actions may better identify superior performance in striking sports. Anaerobic capabilities largely distinguished higher- from lower-level combat sport athletes. In particular, longer-term anaerobic efforts seem to define successful grappling-based athletes, while superior competitors in striking sports tend to show dominance in shorter-term measures when compared with their lower-level counterparts. Given the demand for both forms of combat in MMA, a spectrum of physiological markers may characterize higher-level competitors. Furthermore, the performance profile of successful MMA athletes may differ based on combat sport history or competition strategy. PMID- 26993136 TI - Derivation of the bacterial run-and-tumble kinetic equation from a model with biochemical pathway. AB - Kinetic-transport equations are, by now, standard models to describe the dynamics of populations of bacteria moving by run-and-tumble. Experimental observations show that bacteria increase their run duration when encountering an increasing gradient of chemotactic molecules. This led to a first class of models which heuristically include tumbling frequencies depending on the path-wise gradient of chemotactic signal. More recently, the biochemical pathways regulating the flagellar motors were uncovered. This knowledge gave rise to a second class of kinetic-transport equations, that takes into account an intra-cellular molecular content and which relates the tumbling frequency to this information. It turns out that the tumbling frequency depends on the chemotactic signal, and not on its gradient. For these two classes of models, macroscopic equations of Keller-Segel type, have been derived using diffusion or hyperbolic rescaling. We complete this program by showing how the first class of equations can be derived from the second class with molecular content after appropriate rescaling. The main difficulty is to explain why the path-wise gradient of chemotactic signal can arise in this asymptotic process. Randomness of receptor methylation events can be included, and our approach can be used to compute the tumbling frequency in presence of such a noise. PMID- 26993135 TI - A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury. AB - Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. PMID- 26993138 TI - Colchicine in cardiovascular disease: an ancient drug with modern tricks. AB - From the dark history of being a poison and purgative, colchicine has risen to become one of the few irrefutable positives in the history of pharmacology in the management of myriad inflammatory conditions. Colchicine exerts its action through binding to tubulin, which in turn affects several cellular processes and pathways modulating the inflammatory response. Despite narrow therapeutic toxicity window and the most common complaint of gastrointestinal upset, its list of medicinal use is expanding in recent years as we continue to unravel the mystery of this ancient remedy. In this review, we summarise the history of colchicine use, discuss its pharmacokinetics and mechanism of actions, and examine the most up-to-date evidence of colchicine in the treatment of various cardiac conditions with a focus on cardiovascular disease. PMID- 26993137 TI - Comparison of biological and genomic characteristics between a newly isolated mink enteritis parvovirus MEV-LHV and an attenuated strain MEV-L. AB - A virus isolated from mink showing clinical signs of enteritis was identified as a high virulent mink enteritis parvovirus (MEV) based on its biological characteristics in vivo and in vitro. Mink, challenged with this strain named MEV LHV, exhibited severe pathological lesions as compared to those challenged with attenuated strain MEV-L. MEV-LHV also showed higher infection and replication efficiencies in vitro than MEV-L. Sequence of the complete genome of MEV-LHV was determined and analyzed in comparison with those in GenBank, which revealed that MEV-LHV shared high homology with virulent strain MEV SD12/01, whereas MEV-L was closely related to Abashiri and vaccine strain MEVB, and belonged to a different branch of the phylogenetic tree. The genomes of the two strains differed by insertions and deletions in their palindromic termini and specific unique mutations (especially VP2 300) in coding sequences which may be involved in viral replication and pathogenicity. The results of this study provide a better understanding of the biological and genomic characteristics of MEV and identify certain regions and sites that may be involved in viral replication and pathogenicity. PMID- 26993141 TI - Deep brain stimulation and development of a high-grade glioma: incidental or causal association? AB - We report the case of a patient in whom 8.8 years following the implantation of a bilateral deep brain stimulation (DBS) into the Vim, a high-grade glioma was diagnosed in close proximity to the two electrode leads. A possible relationship between the permanent DBS and the development of the brain tumour is discussed. PMID- 26993140 TI - Neuropathological signs of inflammation correlate with mitochondrial DNA deletions in mesial temporal lobe epilepsy. AB - Accumulation of mitochondrial DNA (mtDNA) deletions has been proposed to be responsible for the presence of respiratory-deficient neurons in several CNS diseases. Deletions are thought to originate from double-strand breaks due to attack of reactive oxygen species (ROS) of putative inflammatory origin. In epileptogenesis, emerging evidence points to chronic inflammation as an important feature. Here we aimed to analyze the potential association of inflammation and mtDNA deletions in the hippocampal tissue of patients with mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS). Hippocampal and parahippocampal tissue samples from 74 patients with drug-refractory mTLE served for mtDNA analysis by multiplex PCR as well as long-range PCR, single-molecule PCR and ultra-deep sequencing of mtDNA in selected samples. Patients were sub-classified according to neuropathological findings. Semi-quantitative assessment of neuronal cell loss was performed in the hippocampal regions CA1-CA4. Inflammatory infiltrates were quantified by cell counts in the CA1, CA3 and CA4 regions from well preserved hippocampal samples (n = 33). Samples with HS showed a significantly increased frequency of a 7436-bp mtDNA deletion (p < 0.0001) and a higher proportion of somatic G>T transversions compared to mTLE patients with different histopathology. Interestingly, the number of T-lymphocytes in the hippocampal CA1, CA3 and CA4 regions was, similar to the 7436-bp mtDNA deletion, significantly increased in samples with HS compared to other subgroups. Our findings show a coincidence of HS, increased somatic G>T transversions, the presence of a specific mtDNA deletion, and increased inflammatory infiltrates. These results support the hypothesis that chronic inflammation leads to mitochondrial dysfunction by ROS-mediated mtDNA mutagenesis which promotes epileptogenesis and neuronal cell loss in patients with mTLE and HS. PMID- 26993142 TI - Clinical experience with navigated 3D ultrasound angiography (power Doppler) in microsurgical treatment of brain arteriovenous malformations. AB - INTRODUCTION: We have previously described a method that has the potential to improve surgery of arteriovenous malformations (AVMs). In the present paper, we present our clinical results. MATERIALS AND METHODS: Of 78 patients referred for AVMs to our University Hospital from our geographical catchment region from 2005 through 2013, 31 patients were operated on with microsurgical technique. 3D MR angiography (MRA) with neuronavigation was used for planning. Navigated 3D ultrasound angiography (USA) was used to identify and clip feeders in the initial phase of the operation. None of our patients was embolized preoperatively as part of the surgical procedure. The niduses were extirpated based on the 3D USA. After extirpation, controls were done with 3D USA to verify that the AVMs were completely removed. The Spetzler three-tier classification of the patients was: A: 21, B: 6, C: 4. RESULTS: Sixty-eight feeders were identified on preoperative MRA and DSA and 67 feeders were identified and clipped by guidance of intraoperative 3D USA. Six feeders identified preoperatively were missed by 3D USA, while five preoperatively unknown feeders were found and clipped. The overall average bleeding was 440 ml. There was a significant reduction in average bleeding in the last 15 operations compared to the first 16 (340 vs. 559 ml, p = 0.019). We had no serious morbidity (GOS 3 or less). New deficits due to surgery were two patients with quadrantanopia (one class B and one class C), the latter (C) also acquired epilepsy. One patient (class A) acquired a hardly noticeable paresis in two fingers. One hundred percent angiographic cure was achieved in all patients, as evaluated by postoperative DSA. CONCLUSIONS: Navigated intraoperative 3D USA is a useful tool to identify and clip AVM feeders. Microsurgical extirpation assisted by navigated 3D USA is an effective and safe method for removing AVMs. PMID- 26993139 TI - Presynaptic dystrophic neurites surrounding amyloid plaques are sites of microtubule disruption, BACE1 elevation, and increased Abeta generation in Alzheimer's disease. AB - Alzheimer's disease (AD) is characterized by amyloid plaques composed of the beta amyloid (Abeta) peptide surrounded by swollen presynaptic dystrophic neurites consisting of dysfunctional axons and terminals that accumulate the beta-site amyloid precursor protein (APP) cleaving enzyme (BACE1) required for Abeta generation. The cellular and molecular mechanisms that govern presynaptic dystrophic neurite formation are unclear, and elucidating these processes may lead to novel AD therapeutic strategies. Previous studies suggest Abeta may disrupt microtubules, which we hypothesize have a critical role in the development of presynaptic dystrophies. To investigate this further, here we have assessed the effects of Abeta, particularly neurotoxic Abeta42, on microtubules during the formation of presynaptic dystrophic neurites in vitro and in vivo. Live-cell imaging of primary neurons revealed that exposure to Abeta42 oligomers caused varicose and beaded neurites with extensive microtubule disruption, and inhibited anterograde and retrograde trafficking. In brain sections from AD patients and the 5XFAD transgenic mouse model of amyloid pathology, dystrophic neurite halos with BACE1 elevation around amyloid plaques exhibited aberrant tubulin accumulations or voids. At the ultrastructural level, peri-plaque dystrophies were strikingly devoid of microtubules and replete with multi lamellar vesicles resembling autophagic intermediates. Proteins of the microtubule motors, kinesin and dynein, and other neuronal proteins were aberrantly localized in peri-plaque dystrophies. Inactive pro-cathepsin D also accumulated in peri-plaque dystrophies, indicating reduced lysosomal function. Most importantly, BACE1 accumulation in peri-plaque dystrophies caused increased BACE1 cleavage of APP and Abeta generation. Our study supports the hypothesis that Abeta induces microtubule disruption in presynaptic dystrophic neurites that surround plaques, thus impairing axonal transport and leading to accumulation of BACE1 and exacerbation of amyloid pathology in AD. PMID- 26993143 TI - Radial forces of stents used in thoracic endovascular aortic repair and bare self expanding nitinol stents measured ex vivo - Rapid rescue for obstruction of the innominate artery using bare self-expanding nitinol stents. AB - Purpose Our objective was to compare the radial forces of several stents ex vivo to identify stents suitable for rescue of the unexpected coverage of aortic arch branches in thoracic endovascular aortic repair. Methods We measured the radial forces of two types of self-expanding bare nitinol stents (E-luminexx and Epic) used singly or as double-walled pairs, and of three endoprostheses used in thoracic endovascular aortic repair (TEVAR, Gore c-TAG, Relay, and Valiant) by compressing the stent using an MTS Instron universal testing machine (model #5582). We also examined the compressive effects of the TEVAR endoprostheses and the bare nitinol stents on each other. Results The radial force was greater in the center than at the edge of each stent. In all stents tested, the radial force decreased incrementally with increasing stent diameter. The radial force at the center was two times greater when using two stents than with a single stent. In the compression test, only E-luminexx used as a pair was not compressed after compressing a Relay endoprosthesis by 12 mm. Conclusion Two E-luminexx stents are appropriate to restore the blood flow if a TEVAR endoprosthesis covers the innominate artery following innominate-carotid-left subclavian arterial bypass. PMID- 26993144 TI - The role of unfractionated heparin for the antiaggregatory effect of aspirin in patients undergoing carotid endarterectomy: Results of an observational clinical study. AB - The aims of the present study were to examine the influence of a low-dose unfractionated heparin regime on platelet aggregation and to additionally assess the prevalence of primary aspirin resistance in patients undergoing carotid endarterectomy. Therefore, 50 patients undergoing carotid endarterectomy were enrolled. A bolus of 3000 IU unfractionated heparin was administered 2 min before carotid cross-clamping additionally to standard antiaggregatory therapy. Haemostaseological point of care testing was performed twice, prior to surgery and 10 min after unfractionated heparin administration by the use of aggregometric and viscoelastic point of care testing. Following unfractionated heparin administration, the activated partial thromboplastin time increased significantly and clotting time in viscoelastic INTEM test was shown to be significantly prolonged. In contrast, the antiaggregatory effect of aspirin was not diminished in aggregometric ASPI test. A low-dose unfractionated heparin regime during carotid endarterectomy was therefore considered to be safe, without diminishing the antiplatelet effect of aspirin. Moreover, aggregometric point of care testing was identified to be a suitable tool for the identification of patients with primary aspirin resistance ( n = 3). PMID- 26993145 TI - Infrared thermography as option for evaluating the treatment effect of percutaneous transluminal angioplasty by patients with peripheral arterial disease. AB - Aim of this study was to evaluate the possible use of infrared thermography as a supplementary method to the ankle-brachial index used in assessing the treatment effect of percutaneous transluminal angioplasty. The study included 21 patients, mean age was 60.22 years. Healthy control group included 20 persons, mean age was 55.60 years. Patients with symptomatic peripheral arterial disease (Fontaine stages I-III) were admitted for endovascular treatment by percutaneous transluminal angioplasty. Thermal images and ankle-brachial index values were obtained before and after treatment by percutaneous transluminal angioplasty. Median temperature change in the treated limb was 0.4C, for non-treated limb was 0.5C. The median value of ankle-brachial index in the treated limb increased by 0.17 from 0.81 after the procedure. The median value of ankle-brachial index in the non-treated limb decreased by 0.03 from the value of 1.01. Significant difference between treated limb and non-treated limb in change of ankle-brachial index was found with p value = .0035. The surface temperature obtained by the infrared thermography correlates with ankle-brachial index. We present data showing that the increase of ankle-brachial index is associated with increase of skin temperature in the case of limbs treated by percutaneous transluminal angioplasty. Our results also suggest potential of the use of infrared thermography for monitoring foot temperature as a means of early detection of onset of foot ischemic disorders. PMID- 26993146 TI - Reducing prognostic errors: a new imperative in quality healthcare. PMID- 26993147 TI - Smartphone Detection of UV LED-Enhanced Particle Immunoassay on Paper Microfluidics. AB - Use of a smartphone as an optical detector for paper microfluidic devices has recently gained substantial attention due to its simplicity, ease of use, and handheld capability. Utilization of a UV light source enhances the optical signal intensities, especially for the particle immunoagglutination assay that has typically used visible or ambient light. Such enhancement is essential for true assimilation of assays to field deployable and point-of-care applications by greatly reducing the effects by independent environmental factors. This work is the first demonstration of using a UV LED (UVA) to enhance the Mie scatter signals from the particle immunoagglutination assay on the paper microfluidic devices and subsequent smartphone detection. Smartphone's CMOS camera can recognize the UVA scatter from the paper microfluidic channels efficiently in its green channel. For an Escherichia coli assay, the normalized signal intensities increased up to 50% from the negative signal with UV LED, compared with the 4% to 7% with ambient light. Detection limit was 10 colony-forming units/mL. Similar results were obtained in the presence of 10% human whole blood. PMID- 26993148 TI - Impact of CMS Competitive Bidding Program on Medicare Beneficiary Safety and Access to Diabetes Testing Supplies: A Retrospective, Longitudinal Analysis. AB - OBJECTIVE: In 2011, the Centers for Medicare & Medicaid Services (CMS) launched the Competitive Bidding Program (CBP) in nine markets for diabetes supplies. The intent was to lower costs to consumers. Medicare claims data (2009-2012) were used to confirm the CMS report (2012) that there were no disruptions in acquisition caused by CBP and no changes in health outcomes. RESEARCH DESIGN AND METHODS: The study population consisted of insulin users: 43,939 beneficiaries in the nine test markets (TEST) and 485,688 beneficiaries in the nontest markets (NONTEST). TEST and NONTEST were subdivided: those with full self-monitoring of blood glucose (SMBG) supply acquisition (full SMBG) according to prescription and those with partial/no acquisition (partial/no SMBG). Propensity score-matched analysis was performed to reduce selection bias. Outcomes were impact of partial/no SMBG acquisition on mortality, inpatient admissions, and inpatient costs. RESULTS: Survival was negatively associated with partial/no SMBG acquisition in both cohorts (P < 0.0001). Coterminous with CBP (2010-2011), there was a 23.0% (P < 0.0001) increase in partial/no SMBG acquisition in TEST vs. 1.7% (P = 0.0002) in NONTEST. Propensity score-matched analysis showed beneficiary migration from full to partial/no SMBG acquisition in 2011 (1,163 TEST vs. 605 NONTEST) was associated with more deaths within the TEST cohort (102 vs. 60), with higher inpatient hospital admissions and associated costs. CONCLUSIONS: SMBG supply acquisition was disrupted in the TEST population, leading to increased migration to partial/no SMBG acquisition with associated increases in mortality, inpatient admissions, and costs. Based on our findings, more effective monitoring protocols are needed to protect beneficiary safety. PMID- 26993149 TI - Risk factors associated with the transmission of carbapenem-resistant Enterobacteriaceae via contaminated duodenoscopes. AB - BACKGROUND AND AIMS: The duodenoscopes used to perform ERCP have been implicated in several outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) infection. The risk factors for CRE transmission via contaminated duodenoscopes remain unclear. METHODS: In this retrospective, single-center, case-control study, all patients who underwent ERCP with either 1 of 2 contaminated duodenoscopes were evaluated. We compared the patients who acquired CRE (active infection or colonization) with those who did not. RESULTS: Between October 3, 2014, and January 28, 2015, a total of 125 procedures were performed on 115 patients by using either of the contaminated duodenoscopes. Culture data were available for 104 of the 115 exposed patients (90.4%). Among these patients, 15 (14.4%) became actively infected (n = 8, 7.7%) or colonized (n = 7, 6.7%) with CRE. On univariate analysis, recent antibiotic exposure (66.7% vs 37.1%; P = .046), active inpatient status (60.0% vs 28.1%; P = .034), and a history of cholangiocarcinoma (26.7% vs 3.4%; P = .008) were patient characteristics associated with an increased risk of CRE infection. Biliary stent placement (53.3% vs 22.5%; P = .024) during ERCP was a significant procedure-related risk factor. After adjusting for cholangiocarcinoma, biliary stent placement (odds ratio 3.62; 95% confidence interval, 1.12-11.67), and active inpatient status (odds ratio 3.74; 95% confidence interval, 1.15-12.12) remained independent risk factors for CRE transmission. CONCLUSIONS: In patients undergoing ERCP with a contaminated duodenoscope, biliary stent placement, a diagnosis of cholangiocarcinoma, and active inpatient status are associated with an increased risk of CRE transmission. PMID- 26993150 TI - Cellular and molecular basis of the imbalance between vascular damage and repair in ageing and age-related diseases: As biomarkers and targets for new treatments. AB - Preclinical and clinical studies suggest that specific subsets of cells isolated from the peripheral blood, play an essential role in the imbalance of damage and repair during age-associated diseases, such as metabolic syndrome, diabetes, atherosclerosis, neurodegenerative diseases, osteoporosis and cancer. Endogenous regeneration of the vessel wall involves cells of the vascular wall, inflammatory cells, circulating precursors, and mature endothelial cells, which are capable to restore the endothelium in a concerted interaction. Early detection of such imbalances with specific biomarkers may reduce age-associated diseases and subsequent cardiovascular events. Likewise, new strategies have the potentiality of acting selectively on these cell populations and co-temporally mediate the stimulation of the function and number of those cell populations with regenerative action on the vessel, and inhibit those able to evocate vascular damage. These strategies may be an alternative innovative way with superior and more efficacy biological effects than conventional attempts used for treating actually vascular diseases, characterizing those co-morbidities related to ageing. PMID- 26993152 TI - HPV prevalence and p16INKa overexpression in non-smoking non-drinking oral cavity cancer patients. AB - OBJECTIVE: Our aim was to compare HPV and p16INK4a (p16) expression and their influence on survival and prognosis in oral cavity squamous cell cancer (OCSCC), between non-smokers and non-drinkers (NSND) and smokers and drinkers (SD). SUBJECTS AND METHODS: Patients with OCSCC treated with surgery from 2000 to 2010 were included in the study. Patients who did not smoke at all or smoked less than 10 pack per years and did not drink alcohol on a daily basis were considered the NSND group. An equal number of SD were the control group. HPV presence was determined from paraffin-embedded blocks investigated by PCR analysis. p16 expression was evaluated with immunohistochemistry. RESULTS: The NSND group were mostly younger or older female patients with tongue or gingival cancers. p16 expression was significantly more frequent in NSND patients (27% vs 10%). Patients with stronger p16 expression had significantly worse survival, especially for tongue cancers (P = 0.026). In Cox multivariate analysis, both HPV and p16 expression carried a negative prognosis for NSND patients (P = 0.0351 and P = 0.0260). CONCLUSIONS: NSND are a specific population of OCSCC patients. In contrast to oropharyngeal cancer, HPV and p16 expression in OCSCC are negative predictive factors, especially in NSND patients. PMID- 26993151 TI - The Behavioral Economics and Neuroeconomics of Alcohol Use Disorders. AB - BACKGROUND: Behavioral economics and neuroeconomics bring together perspectives and methods from psychology, economics, and cognitive neuroscience to understand decision making and choice behavior. Extending an operant behavioral theoretical framework, these perspectives have increasingly been applied to understand the alcohol use disorders (AUDs), and this review surveys the theory, methods, and findings from this approach. The focus is on 3 key behavioral economic concepts: delay discounting (i.e., preferences for smaller immediate rewards relative to larger delayed rewards), alcohol demand (i.e., alcohol's reinforcing value), and proportionate alcohol-related reinforcement (i.e., relative amount of psychosocial reinforcement associated with alcohol use). FINDINGS: Delay discounting has been linked to AUDs in both cross-sectional and longitudinal studies and has been investigated cross-sectionally using neuroimaging. Alcohol demand and proportionate alcohol-related reinforcement have both been robustly associated with drinking and alcohol misuse cross-sectionally, but not over time. Both have also been found to predict treatment response to brief interventions. Alcohol demand has also been used to enhance the measurement of acute motivation for alcohol in laboratory studies. Interventions that focus on reducing the value of alcohol by increasing alternative reinforcement and response cost have been found to be efficacious, albeit in relatively small numbers of randomized controlled trials (RCTs). Mediators and moderators of response to these interventions have not been extensively investigated. FUTURE DIRECTIONS: The application of behavioral economics and neuroeconomics to AUDs has given rise to an extensive body of empirical work, although significant gaps in knowledge remain. In particular, there is a need for more longitudinal investigations to clarify the etiological roles of these behavioral economic processes, especially alcohol demand and proportionate alcohol reinforcement. Additional RCTs are needed to extend and generalize the findings for reinforcement-based interventions and to investigate mediators and moderators of treatment success for optimization. Applying neuroeconomics to AUDs remains at an early stage and has been primarily descriptive to date, but has high potential for important translational insights into the future. The same is true for using these behavioral economic indicators to understand genetic influences on AUDs. PMID- 26993155 TI - Does "6-Clicks" Day 1 Postoperative Mobility Score Predict Discharge Disposition After Total Hip and Knee Arthroplasties? AB - BACKGROUND: The use of inpatient rehabilitation services after total joint arthroplasty (TJA) is an important driver of episode-of-care costs. We determined the utility of a new standardized instrument collected during the immediate postoperative period, the Activity Measure for Post-Acute Care (AM-PAC) "6 Clicks" Mobility score, in predicting discharge disposition after TJA and its accuracy in estimating prolonged hospital stay, readmissions, and emergency department (ED) visits. METHODS: Using our institutional database, we retrospectively reviewed 744 patients undergoing primary total hip (40%) or knee (60%) arthroplasty for osteoarthritis during 2014. The AM-PAC Mobility score was prospectively collected by physical therapists within 24 hours of surgery. We constructed 2 multivariable logistic regression models for each study outcome: (1) a base model containing age, sex, Charlson Comorbidity Index, and procedure type and (2) the AM-PAC model including the aforementioned variables and this score. The predictive performance of these models was assessed and compared using the area under the receiver operating characteristic (AUC) curve. RESULTS: The AM PAC model provided better prediction of discharge disposition (AUC = 0.777) than the base model (AUC = 0.716; 22% relative improvement). Although the AM-PAC model performed 32% and 27% better than the base model in estimating prolonged hospital stay and ED visits, the model's predictive performance was poor (prolonged stay: AUC = 0.639; ED visit: AUC = 0.658). The AM-PAC model also showed poor discrimination of readmissions (AUC = 0.657), and there was no relative improvement in predictive performance compared to that of the base model. CONCLUSION: The AM-PAC "6-Clicks" Mobility score is a valid, simple tool for predicting discharge disposition after TJA. PMID- 26993153 TI - Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions. AB - Werner syndrome (WS) is a prototypical segmental progeroid syndrome characterized by multiple features consistent with accelerated aging. It is caused by null mutations of the WRN gene, which encodes a member of the RECQ family of DNA helicases. A unique feature of the WRN helicase is the presence of an exonuclease domain in its N-terminal region. Biochemical and cell biological studies during the past decade have demonstrated involvements of the WRN protein in multiple DNA transactions, including DNA repair, recombination, replication and transcription. A role of the WRN protein in telomere maintenance could explain many of the WS phenotypes. Recent discoveries of new progeroid loci found in atypical Werner cases continue to support the concept of genomic instability as a major mechanism of biological aging. Based on these biological insights, efforts are underway to develop therapeutic interventions for WS and related progeroid syndromes. PMID- 26993154 TI - Aging in two languages: Implications for public health. AB - With the population aging and a dramatic increase in the number of senior citizens, public health systems will be increasingly burdened with the need to deal with the care and treatment of individuals with dementia. We review evidence demonstrating how a particular experience, bilingualism, has been shown to protect cognitive function in older age and delay onset of symptoms of dementia. This paper describes behavioral and brain studies that have compared monolingual and bilingual older adults on measures of cognitive function or brain structure and reviews evidence demonstrating a protective effect of bilingualism against symptoms of dementia. We conclude by presenting some data showing the potential savings in both human costs in terms of demented patients and economic considerations in terms of public money if symptoms of dementia could be postponed. PMID- 26993157 TI - Immature platelet fraction: a significant platelet parameter in asymptomatic constitutional macrothrombocytopenia. PMID- 26993156 TI - A prognostic model for platinum-doublet as second-line chemotherapy in advanced non-small-cell lung cancer patients. AB - Poor prognosis of advanced non-small-cell lung cancer (NSCLC) patients and the promising therapeutic effect of platinum urge the oncologists to evaluate the role of platinum doublet as second-line chemotherapy and establish the definition of platinum sensitivity in NSCLC. We retrospectively analyzed 364 advanced NSCLC patients who received platinum-doublet regimens as second-line chemotherapy after platinum-based first-line treatment. Patients were divided into four groups by their time-to-progression (TTP) after first-line chemotherapy: 0-3, 4-6, 7-12, and >12-month group, respectively. Treatment efficacy of patients' overall survival (OS), progression-free survival (PFS), and response rate (RR), as well as treatment-related toxicity, were compared among the four groups. A prognosis score system and a nomogram were established by Cox proportional hazard model, and validated by concordance index (c-index). Median OS was 14.0, 16.0, 20.0, 25.0 months for patients in the 0-3, 4-6, 7-12, >12-month group, respectively. Age <=60 years (P = 0.002), female (P = 0.019), and TTP>12 months (P = 0.003) were independent prognostic factors. Prognostic score was calculated by adding 1 point each for any of the above three indicators, with a c-index of 0.590 (95% confidential interval [CI], 0.552-0.627). Median OS were equal to 25.0, 16.0, and 11.0 months for best (2-3 points), intermediate (1 point) and worst (0 point) category, respectively (P < 0.0001). A nomogram that integrated patient's age, gender, and TTP for OS has a c-index of 0.623 (95% CI, 0.603-0.643). Female, younger than 60 years, and TTP greater than 12 months may indicate prolonged survival after platinum-doublet second-line chemotherapy in advanced NSCLCpatients. PMID- 26993158 TI - A 10-year follow-up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing. AB - BACKGROUND: Most patients with xeroderma pigmentosum complementation group D (XP D) from Western countries suffer from neurological symptoms, whereas Japanese patients display only skin manifestations without neurological symptoms. We have previously suggested that these differences in clinical manifestations in XP-D patients are attributed partly to a predominant mutation in ERCC2, and the allele frequency of S541R is highest in Japan. METHODS: We diagnosed a child with mild case of XP-D by the evaluation of DNA repair activity and whole-genome sequencing, and followed her ten years. RESULTS: Skin cancer, mental retardation, and neurological symptoms were not observed. Her minimal erythema dose was 41 mJ/cm(2) , which was slightly lower than that of healthy Japanese volunteers. The patient's cells showed sixfold hypersensitivity to UV in comparison with normal cells. Post-UV unscheduled DNA synthesis was 20.4%, and post-UV recovery of RNA synthesis was 58% of non-irradiated samples, which was lower than that of normal fibroblasts. Genome sequence analysis indicated that the patient harbored a compound heterozygous mutation of c.1621A>C and c.591_594del, resulting in p.S541R and p.Y197* in ERCC2: then, patient was diagnosed with XP-D. Y197* has not been described before. CONCLUSION: Her mild skin manifestations might be attributed to the mutational site on her genome and daily strict sun protection. c.1621A>C might be a founder mutation of ERCC2 among Japanese XP-D patients, as it was identified most frequently in Japanese XP-D patients and it has not been found elsewhere outside Japan. PMID- 26993159 TI - The incidence and importance of anaemia in patients undergoing cardiac surgery in the UK - the first Association of Cardiothoracic Anaesthetists national audit. AB - The importance and variability of pre-operative anaemia in cardiac surgical patients across the UK is not known, and there is debate about its association with patient outcomes. The Association of Cardiothoracic Anaesthetists carried out its first national audit on anaemia and transfusion, and analysed data from 19,033 patients operated on in 12 cardiac surgical centres between 2010 and 2012; 5895 (31%) had pre-operative anaemia. Centre-specific prevalence of anaemia varied from 23% to 45%; anaemia was associated with older patients, diabetes and surgical risk (EuroSCORE). Nevertheless, controlling for these factors, regional variation remained an independent effect (p < 0.001). Multivariable analysis demonstrated an independent association of anaemia with transfusion (odds ratio (95% confidence interval) 2.75 (2.55-2.95), p < 0.001), mortality (1.42 (1.18 1.71), p < 0.001) and hospital stay (geometric mean ratio (95% confidence interval) 1.15 (1.13-1.17), p < 0.001). Haemoglobin concentration per se was also independently associated with worse outcomes; a 10 g.l(-1) decrease in haemoglobin was associated with a 43% increase (95% confidence interval 40-46%) in the odds of transfusion and a 16% increase (95% confidence interval 10-22%) in the odds of mortality (both p < 0.001). This large UK-wide audit has demonstrated marked regional variation in both anaemia and transfusion, with a consistently high incidence of both. The independent association between pre-operative anaemia and worse outcomes in UK practice has also been confirmed, and robust prospective study of anaemia treatment before cardiac surgery is required; these data will assist in designing such trials. PMID- 26993160 TI - Association between follicular gastritis and Helicobacter pylori in children seen at a public hospital in Peru. AB - BACKGROUND: For the last 15 years, infection from Helicobacter pylori (H. pylori) has been recognized in gastritis pathogenesis, and is known to trigger an important inflammatory response in these patients. AIM: To determine the association between follicular gastritis and H. pylori infection in children seen at a public hospital in Peru. METHODOLOGY: An analytic, cross-sectional study was conducted on all the children treated at the Hospital Nacional Docente Madre "Nino San Bartolome" in Lima, Peru, within the time frame of 2011-2012. All the personal data from the patients' medical histories and endoscopic procedures were collected. The crude prevalence ratios (PR) were obtained and adjusted (aPR) with their 95% confidence intervals (95%CI), using generalized linear models with the binomial family and log link function. RESULTS: A total of 123 children met the study criteria. Forty-eight (39%) of the study sample were girls and the mean age of the children was 12 years. H. pylori was present in 44% of the sample and 9% presented with more than 100 bacteria per field (classified as +++). Thirty-five percent of the children had esophagitis due to concomitant reflux. The presence of H. pylori was associated with follicular gastritis (P<0.01; aPR: 2.3; 95% CI:1.49-3.49), adjusted by the children's age. CONCLUSIONS: Based on the data analyzed, it was concluded that the children with follicular gastritis had a greater likelihood of having H. pylori than those that did not present with gastritis. These results can be extrapolated to other similar populations and should be evaluated in each setting so that this does not become a public health problem within the next few years. PMID- 26993161 TI - Papillary adenoma of the common bile duct: Infrequent pathology, novel endoscopic resolution, rare complication. A case report. PMID- 26993162 TI - FGFR antagonist induces protective autophagy in FGFR1-amplified breast cancer cell. AB - Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. PMID- 26993163 TI - Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells. AB - Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. PMID- 26993164 TI - Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension. AB - Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called "priming" factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 MUM C1P showed improved migration activity in Transwell assays compared with non primed MSCs and concomitantly activated MAPK(p42/44) and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of alpha-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients. PMID- 26993165 TI - Blockage of progestin physiology disrupts ovarian differentiation in XX Nile tilapia (Oreochromis niloticus). AB - Previous studies indicated that maturation inducing hormone, 17alpha, 20beta Dihydroxy-4-pregnen-3-one (DHP), probably through nuclear progestin receptor (Pgr), might be involved in spermatogenesis and oogenesis in fish. To further elucidate DHP actions in teleostean ovarian differentiation, we analyzed the expression of pgr in the ovary of Nile tilapia (Oreochromis niloticus), and performed RU486 (a synthetic Pgr antagonist) treatment in XX fish from 5 days after hatching (dah) to 120 dah. Tilapia Pgr was abundantly expressed in the follicular cells surrounding oocytes at 30 and 90 dah. Continuous RU486 treatment led to the blockage of oogenesis and masculinization of somatic cells in XX fish. Termination of RU486 treatment and maintenance in normal condition resulted in testicular differentiation, and estrogen compensation in RU486-treated XX fish successfully restored oogenesis. In RU486-treated XX fish, transcript levels of female dominant genes were significantly reduced, while male-biased genes were evidently augmented. Meanwhile, both germ cell mitotic and meiotic markers were substantially reduced. Consistently, estrogen production levels were significantly declined in RU486-treated XX fish. Taken together, our data further proved that DHP, possibly through Pgr, might be essential in the ovarian differentiation and estrogen production in fish. PMID- 26993166 TI - Cell enrichment-free massive ex-vivo expansion of peripheral CD20+ B cells via CD40-CD40L signals in non-human primates. AB - Non-human primates (NHPs) are valuable as preclinical resources that bridge the gap between basic science and clinical application. B cells from NHPs have been utilized for the development of B-cell targeted drugs and cell-based therapeutic modalities; however, few studies on the ex-vivo expansion of monkey B cells have been reported. In this study, we developed a highly efficient ex-vivo expansion protocol for monkey B cells resulting in 99% purity without the requirement for prior cell-enrichment procedures. To this end, monkey peripheral blood mononuclear cells (PBMCs) were stimulated for 12 days with cells constitutively expressing monkey CD40L in expansion medium optimized for specific and massive expansion of B cells. The B cells expansion rates obtained were 2-5 times higher than those previously reported in humans, with rates ranging from 7.9 to 16.6 fold increase. Moreover, expanded B cells sustained high expression of co stimulatory molecules including CD83 and CD86 until day 12 of culture, and the simple application of a brief centrifugation resulted in a CD20(+) B cell purity rate of greater than 99%. Furthermore, small amounts of CD3(+)CD20(+)BT-like cells were generated and CD16 was expressed at moderate levels on expanded B cells. Thus, the establishment of this protocol provides a method to produce quantities of homogeneous, mature B cells in numbers sufficient for the in vitro study of B cell immunity as well as for the development of B cell-diagnostic tools and cell-based therapeutic modalities. PMID- 26993167 TI - Noncanonical function of threonyl-tRNA synthetase regulates vascular development in zebrafish. AB - The canonical functions of Aminoacyl-tRNA synthetases (AARSs) are indispensable for protein synthesis. However, recent evidence indicates that some AARSs possess additional biological functions (noncanonical functions) related to immune responses and vascular development. Here, we identified a zebrafish cq16 mutant presenting the disorganized vessels with abnormal branching of the established intersegmental vessels (ISVs) as well as aberrant patterning of the brain vascular network after 50 h post fertilization. The cq16 mutant gene is responsible for encoding threonyl-tRNA synthetase (tars) with a missense mutation. The abnormal branching of ISVs was caused by the increased expression of vascular endothelial growth factor A (vegfa) in tars(cq16) mutant. Inhibition of Vegf signaling suppresses the abnormal vascular branching observed in tars(cq16) mutant. Furthermore, injection of human TARS mRNA potently reduced the vascular aberrant branching in tars(cq16) mutant, indicating a conserved function of tars in regulating angiogenesis between zebrafish and human. Therefore, we conclude that noncanonical function of tars regulates vascular development presumably by modulating the expression of vegfa. PMID- 26993169 TI - Mutational analysis in patients with neuromuscular disorders: Detection of mitochondrial deletion and double mutations in the MT-ATP6 gene. AB - Mitochondrial diseases encompass a wide variety of pathologies characterized by a dysfunction of the mitochondrial respiratory chain resulting in an energy deficiency. The respiratory chain consists of five multi-protein complexes providing coupling between nutrient oxidation and phosphorylation of ADP to ATP. In the present report, we studied mitochondrial genes of complex I, III, IV and V in 2 Tunisian patients with mitochondrial neuromuscular disorders. In the first patient, we detected the m.8392C>T variation (P136S) in the mitochondrial ATPase6 gene and the m.8527A>G transition at the junction MT-ATP6/MT-ATP8 which change the initiation codon AUG to GUG. The presence of these two variations in such an important gene could probably affect the ATP synthesis in the studied patient. In the second patient, we detected several known variations in addition to a mitochondrial deletion in the major arc of the mtDNA eliminating tRNA and respiratory chain protein genes. This deletion could be responsible of an inefficient translation leading to an inefficient mitochondrial protein synthesis in P2. PMID- 26993168 TI - Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy. AB - Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period of pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. PMID- 26993170 TI - Pollen used to produce allergen extracts. AB - OBJECTIVE: To review the use of pollen for the production of allergen extracts to diagnose and treat allergic diseases, examine the associated regulations, and highlight candidate areas for improvement. DATA SOURCES: A PubMed search was performed using focused keywords combined with a review of regulatory documents and industry guidelines. STUDY SELECTIONS: The information obtained through literature, documents, and industry was scrutinized and used with personal experience and expertise to write this article. RESULTS: Both genetic and environmental factors affect the allergenic composition of pollen because it is a biologically active pharmaceutical ingredient obtained from nature. The potential effect of airborne contaminants in pollen requires major attention but can be properly addressed through careful collection practices, combined with a proper interpretation of the data on purity obtained for each pollen lot. The regulations associated with pollen used to manufacture allergen extracts in the United States and Europe and the numbers of pollen allergen extracts commercially available in both areas of the world differ. A critical parameter to select the appropriate extracts for diagnosis and allergen immunotherapy is to understand the phenomenon of cross-reactivity among pollen families, genera, and species. CONCLUSION: Physicians should be aware of the factors responsible for the qualitative and quantitative composition of pollen allergen extracts and the associated regulations to produce suitable extracts to diagnose and treat allergic diseases. Collaboration and cooperation among allergen manufacturing companies and regulatory agencies are necessary. PMID- 26993171 TI - Stinging insect identification: Are the allergy specialists any better than their patients? AB - BACKGROUND: It has been reported that the general population is not skillful at identifying stinging insects with the exception of the honeybee. No information is available to evaluate allergy physicians' accuracy with stinging insect identification. OBJECTIVE: To measure the accuracy of allergists' ability to identify stinging insects and assess their common practices for evaluating individuals with suspected insect hypersensitivity. METHODS: A picture-based survey and a dried specimen insect box were constructed to determine allergists' and nonallergists' accuracy in identifying insects. Allergists attending the 2013 American College of Allergy, Asthma, and Immunology meeting were invited to participate in the study. Common practice approaches for evaluating individuals with stinging insect hypersensitivity were also investigated using a brief questionnaire. RESULTS: Allergy physicians are collectively better at insect identification than nonallergists. Overall, the mean (SD) number of correct responses for nonallergists was 5.4 (2.0) of a total of 10. This score was significantly lower than the score for allergists (6.1 [2.0]; P = .01) who participated in the study. Most allergists (78.5%) test for all stinging insects and use skin testing (69.5%) as the initial test of choice for evaluating individuals with insect hypersensitivity. CONCLUSION: Overall, allergists are more skilled at Hymenoptera identification. Most allergy specialists reported testing for all stinging insects when evaluating insect hypersensitivity, and skin testing was the preferred testing method in nearly 70% of allergists. These data support the practice parameter's recommendation to consider testing for all flying Hymenoptera insects during venom evaluation, which most of the participating allergists surveyed incorporate into their clinical practice. PMID- 26993172 TI - Bacteria may induce the secretion of mucin-like proteins by the diatom Phaeodactylum tricornutum. AB - Benthic diatoms live in photoautotrophic/heterotrophic biofilm communities embedded in a matrix of secreted extracellular polymeric substances. Closely associated bacteria influence their growth, aggregation, and secretion of exopolymers. We have studied a diatom/bacteria model community, in which a marine Roseobacter strain is able to grow with secreted diatom exopolymers as a sole source of carbon. The strain influences the aggregation of Phaeodactylum tricornutum by inducing a morphotypic transition from planktonic, fusiform cells to benthic, oval cells. Analysis of the extracellular soluble proteome of P. tricornutum in the presence and absence of bacteria revealed constitutively expressed newly identified proteins with mucin-like domains that appear to be typical for extracellular diatom proteins. In contrast to mucins, the proline-, serine-, threonine-rich (PST) domains in these proteins were also found in combination with protease-, glucosidase- and leucine-rich repeat-domains. Bioinformatic functional predictions indicate that several of these newly identified diatom-specific proteins may be involved in algal defense, intercellular signaling, and aggregation. PMID- 26993173 TI - Blood stream infections caused by Acinetobacter baumannii group in Japan - Epidemiological and clinical investigation. AB - Acinetobacter calcoaceticus-Acinetobacter baumannii complex, especially A. baumannii, Acinetobacter pittii and Acinetobacter nosocomialis, constitutes an important group of nosocomial pathogens; however, epidemiological or clinical characteristics and prognosis is limited in Japan. From 2009 to 2013, 47 blood stream infection cases resulting from A. baumannii group were reviewed at the National Defense Medical College, an 800-bed tertiary hospital. To determine the genospecies, further comparative nucleotide sequence analyses of the RNA polymerase b-subunit (rpoB) gene were performed. Sequence analysis of rpoB gene showed that 25 (49.0%), 17 (33.3%) and 5 (9.8%) cases were caused by A. baumannii, A. pittii and A. nosocomialis, respectively. The 30-day and in hospital mortality rates of A. baumannii were 8.5% and 25.5%, respectively, and there were no significant differences between Acinetobacter species. Clinical characteristics were statistically insignificant. Multidrug-resistant Acinetobacter species were detected in 3 cases (5.9%) with same pulsed-field gel electrophoresis (PFGE) pattern and A. baumannii was less susceptible to amikacin and levofloxacin. In this study, the mortality and clinical characteristics were similar among A. baumannii group isolate cases despite some showing drug resistance. However, identification of Acinetobacter species helps to initiate appropriate antibiotic therapy in earlier treatment phase, because A. baumannii shows some drug resistance. PMID- 26993174 TI - Rapid diagnostic method for the identification of Mycoplasma pneumoniae respiratory tract infection. AB - Rapid diagnostic tests are useful tools in the early diagnosis of respiratory tract infections (RTIs) caused by a specific pathogens. We investigated the sensitivity and specificity of a rapid and simple antigen test for the detection of Mycoplasma pneumoniae, Ribotest Mycoplasma((r)) in adolescent and adult patients with RTIs. In addition, we evaluated the accuracy of clinical and laboratory findings for the early presumptive diagnosis of M. pneumoniae RTI. We compared 55 cases with laboratory-confirmed M. pneumoniae infection using serology, culture, and polymerase chain reaction (PCR) and 346 cases without laboratory-confirmed M. pneumoniae infection. Pneumonia cases were excluded in this study. Among patients with M. pneumoniae infection, the incidences of cough, sore throat, and sputum production were high, with rates of 98%, 61%, and 67%, respectively, but the specificity was low. The prevalence of nasal symptoms was significantly lower in patients with M. pneumoniae infection (9%) than in non-M. pneumoniae infection (70%; p < 0.0001). When PCR was used as the control test, the sensitivity, specificity, and overall agreement rates with Ribotest((r)) were 71%, 89%, and 87%, respectively. Clinical symptoms and laboratory data were of limited value in making the diagnosis of M. pneumoniae RTI in adolescent and adult patients. Our results suggested that Ribotest((r)) may be helpful in distinguishing M. pneumoniae RTI patients from those without the disease. Physicians should consider the use of Ribotest((r)) when patients have a persistent cough without nasal symptoms. PMID- 26993175 TI - Aurora B inhibitor barasertib prevents meiotic maturation and subsequent embryo development in pig oocytes. AB - Barasertib, a highly selective Aurora B inhibitor, has been widely used in a variety of cells to investigate the role of Aurora B kinase, which has been implicated in various functions in the mitotic process. However, effects of barasertib on the meiotic maturation process are not fully understood, particularly in porcine oocyte meiotic maturation. In the present study, the effects of barasertib on the meiotic maturation and developmental competence of pig oocytes were investigated, and the possible roles of Aurora B were also evaluated in porcine oocytes undergoing meiosis. Initially, we examined the expression and subcellular localization of Aurora B using Western blot analysis and immunofluorescent staining. Aurora B was found to express and exhibit specific dynamic intracellular localization during porcine oocyte meiotic maturation. Aurora B was observed around the chromosomes after germinal vesicle breakdown. Then it was transferred to the spindle region after metaphase I stage, and was particularly concentrated at the central spindles at telophase I stage. barasertib treatment resulted in the failure of polar body extrusion in pig oocytes, with a larger percentage of barasertib-treated oocytes remaining at the pro-metaphase I stage. Additional results reported that barasertib treatment had no effect on chromosome condensation but resulted in a significantly higher percentage of the treated oocytes with aberrant spindles and misaligned chromosomes during the first meiotic division. In addition, inhibition of Aurora B with lower concentrations of barasertib during pig oocyte meiotic maturation decreased the subsequent embryo developmental competence. Thus, these results illustrate that barasertib has significant effects on porcine oocyte meiotic maturation and subsequent development through Aurora B inhibition, and this regulation is related to its effects on spindle formation and chromosome alignment during the first meiotic division in porcine oocytes. PMID- 26993176 TI - Residual rates of reflux and obstruction and their correlation to post-thrombotic syndrome in a randomized study on catheter-directed thrombolysis for deep vein thrombosis. AB - BACKGROUND: Deep vein thrombosis (DVT) often results in venous valvular incompetence and incomplete recanalization, followed by post-thrombotic syndrome (PTS). Treatment with additional catheter-directed thrombolysis (CDT) in patients with an iliofemoral DVT has been shown to reduce the frequency of PTS. The objective of this study was to assess the effect of CDT on venous reflux and patency and to identify possible predictors for the development of PTS. METHODS: Open, multicenter, randomized, controlled clinical trial. Patients (18-75 years) with a first-time iliofemoral DVT were randomized to receive conventional treatment with anticoagulation and compression stockings or CDT in addition to conventional treatment. Follow-up after 6 and 24 months included ultrasound and air plethysmography for evaluation of venous reflux and patency. PTS was assessed with the Villalta score. Possible predictors of PTS were analyzed in multivariate logistic regression models. RESULTS: Following additional CDT, deep venous reflux was detected in 65.2% (95% confidence interval [CI], 54.8-74.2) of patients at 6 months and 66.7% (95% CI, 56.4-75.6) at 24 months. The absolute risk reduction of deep venous reflux was 11.9% (95% CI, 1.1-24.9) after 6 months and 16.5% (95% CI, 4.2-28.8) after 24 months in the CDT arm compared with controls. Correspondingly, venous patency was regained in 65.9% (95% CI, 55.5-75.0) of patients at 6 months and 74.7% (95% CI, 64.9-82.6) after 24 months. Patency was regained in 18.5% (95% CI, 4.4-32.6) more patients after 6 months and 15.1% (95% CI, 1.8-28.5) more patients after 24 months compared with controls. Independent of treatment allocation, patients with fully recanalized and competent deep veins at 6-month follow-up had a 40.5% (95% CI, 26.4-54.7) absolute risk reduction of developing PTS compared with patients with abnormal vein assessment. Reflux and lack of patency at 6 months were found to be independent predictors of PTS development in patients treated with CDT (odds ratio, 8.3; 95% CI, 2.6-26.8 for patients with reflux, and odds ratio, 0.17; 95% CI, 0.06-0.49 for patients with patency). CONCLUSIONS: Additional CDT improved patency and reduced reflux. Both parameters were found to be strong predictors of PTS in patients treated with CDT. Noninvasive vein assessments of patency and reflux may be helpful to identify and monitor patients at high risk of PTS. Our findings provide evidence for the importance of early recanalization with CDT for acute iliofemoral DVT. PMID- 26993177 TI - Prevalence of established risk factors for venous thromboembolism according to age. AB - OBJECTIVE: To date, the factors that contribute to the rise in venous thromboembolism (VTE) risk observed with higher ages remain unknown. Therefore, the aim of the present analysis was to study the distribution of established VTE risk factors in categories of manifestation age in a large cohort of VTE patients. METHODS: Data were taken from the MAISTHRO (MAin-ISar-THROmbosis) registry, a cross-sectional study of patients with acute or documented history of VTE. The registry enrolled 1500 consecutive patients (869 females; median age, 43 years) with a first lower-extremity deep vein thrombosis or pulmonary embolism. RESULTS: VTE was attributed to established risk factors in 76.6% of cases. By classifying patients into categories of VTE manifestation age, we observed a steep rise in the prevalence of malignancies with advancing age (ie, 1.3% of cases of VTE occurred under the age of 30 and 34.0% of VTE cases manifested over the age of 70; P < .001). In contrast, VTE was more likely to be related to thrombophilia, a family history of VTE, oral contraceptives, and pregnancy in younger patients. Hereditary thrombophilia was detected in 50% of VTE patients younger than 20 and in 21.8% over the age of 70 (P < .001). With regard to other VTE risk factors, the results were insignificant. In addition, we were unable to demonstrate an accumulation of common VTE risk factors among patients at higher ages. CONCLUSIONS: The distribution of established VTE risk factors varies with the age of VTE manifestation. Future studies are needed to clarify the role of age-specific risk factors in the development of VTE and in the incidence gradient with aging. PMID- 26993178 TI - Measurement of thrombus resolution using three-dimensional ultrasound assessment of deep vein thrombosis volume. AB - OBJECTIVE: Current imaging techniques are limited in their ability to quantify thrombus burden, progression, resolution, and organization over time in patients with acute deep vein thrombosis (DVT). These assessments are critical measures of therapeutic success when thrombolytic or thrombectomy treatment protocols are utilized for DVT. We evaluated the reliability of a new, commercially available method of acquiring and analyzing three-dimensional (3D) ultrasound images of DVTs that measures thrombus volume and echogenicity. METHODS: We studied 25 consecutive hospital in-patients (18 male, seven female; age range, 37-87 years) with a first episode of acute DVT. Treatment decisions were not influenced by the study protocol. Scanning was performed independently by two sonographers, then the first sonographer repeated the scan. A combination of routine imaging in grayscale, color-flow, and power-Doppler modes (2D transducer) along with volumetric imaging (3D transducer) was performed. Patients underwent imaging at baseline and on one or more follow-up days 7, 14, 21 and 30. Image-processing software loaded on the ultrasound machine was used to obtain thrombus volume and echogenicity measurements. RESULTS: Thrombus volume was reliably determined by our protocol. The median volume of thrombus at baseline was 0.4 cm(3). Mean inter and intraobserver differences in volume measurements were 0.006 +/- 0.26 cm(3) and -0.12 +/- 0.29 cm(3) (mean +/- standard deviation). Thrombus resolved over time at a rate of -0.042 +/- 0.01 cm(3)/day (P < .003). The median echogenicity of thrombus at baseline expressed as the grayscale median value was 59. There was a trend for thrombus organization (measured as echogenicity) to increase with time, +0.36 +/- 0.23 grayscale median units/day (P < .13). Adjustment for the use of anticoagulation, gender of subject, or location of DVT in the upper vs lower extremity did not alter the relationship between time and volume or time and echogenicity. CONCLUSIONS: We describe a 3D imaging protocol that reliably measures thrombus volume and echogenicity over time. The method is convenient and can be utilized in routine clinical practice. Acute DVT was associated with a reduction in thrombus size and trend for increased echogenicity over 1 month. This protocol will be of increasing value as our appreciation for the deleterious effects of residual thrombus after DVT increases and our utilization of aggressive thrombus removal treatments for acute DVT increases. PMID- 26993179 TI - Assessment of residual thrombus after venous thrombolytic regimens. AB - BACKGROUND: We noticed substantial residual thrombus on intravascular ultrasound (IVUS) in many limbs despite restoration of flow after thrombolysis. Since thrombus burden has been tied to post-thrombotic syndrome (PTS), the frequency and extent of residual thrombus after thrombolysis is important. We present such an analysis below. METHODS: Sixty-seven limbs underwent (median age, 57; range, 24-83) pharmacomechanical thrombectomy (PMT) after deep venous thrombosis (DVT) (35 limbs) or iliac vein stent thrombosis (32 limbs). Assessment after PMT included venography and IVUS. If flow was not established or residual thrombus was present on IVUS examination, follow-up catheter-directed thrombolysis (CDT) up to 3 days was used to clear the thrombus. RESULTS: PMT was successful in establishing flow across occluded segments in 82%, but complete lysis per IVUS was achieved in only 9% with residual thrombus present in 91% (18% occlusive) of treated limbs. Follow-up CDT was feasible in 48 limbs. This resulted in establishment of inline flow in nine additional limbs; complete thrombus clearance per IVUS was achieved in 15 others (many with prior inline flow with thrombus). Overall, 96% of limbs were patent, but as many as 69% of limbs had residual thrombus after treatment with one or both lytic regimens. There was significantly more complete clot clearance (P < .04) in virgin DVT compared with thrombosis in stented limbs. IVUS was significantly more sensitive (P = .03) than venography in estimating residual thrombus burden. However, there was no significant difference in PTS incidence whether the clot was completely lysed or not. CONCLUSIONS: Venographic patency can be established in most limbs with DVT or stent thrombosis by PMT alone. Venographic patency was a poor guide to the presence and extent of residual thrombus. Follow-up CDT was useful in significantly increasing complete clot clearance, but residual thrombus remained on IVUS in over two-thirds of treated limbs overall. The implications of residual thrombus after inline flow has been re-established with thrombolytic regimens for the development of PTS are unknown. PMID- 26993180 TI - Activated protein C resistance associated with lupus anticoagulants is a high risk in acute mesenteric venous thrombosis. AB - BACKGROUND: Acute mesenteric venous thrombosis (AMVT) is one of those diseases that cannot be diagnosed by specific symptoms and signs. A high misdiagnosis rate makes AMVT a final diagnosis established by exploratory laparotomy or forensic examinations earlier, during the period when computed tomography was not as efficient as it is now. The main motivation of our research was to improve the diagnosis and treatment by finding the relationship among activated protein C (APC) resistance, antiphospholipid antibodies, and AMVT in the Chinese Han population. METHODS: APC resistance was tested by activated partial thromboplastin time method in 70 AMVT patients and 75 healthy adult volunteers that excluded hypercoagulable states. Factor V Leiden mutation was analyzed by polymerase chain reaction with restriction fragment length polymorphism. Anticardiolipin antibodies (aCLs) were tested by enzyme-linked immunosorbent assay. A sensitive activated partial thromboplastin time-lupus anticoagulant (LA) test was used according to the guidelines. RESULTS: Only two samples had factor V Leiden mutation and were excluded. Twenty-one (30.9%) of the 68 AMVT patients had APC resistance. The rate of aCLs positive in AMVT group (13.2%) was significantly increased compared with control group (1.33%; P = .014). The LA-positive rate is significantly different between the AMVT and control group. Among LA-positive patients, the number of APC resistance was much higher than LA-negative patients (P = .000), but aCLs do not have an increased predisposition to APC resistance (P = .85). CONCLUSIONS: APC resistance associated with LAs is a high risk in AMVT. The way aCL may affect the process of AMVT is not the same as with LA. PMID- 26993181 TI - The effectiveness of a novel neuromuscular electrostimulation method versus intermittent pneumatic compression in enhancing lower limb blood flow. AB - OBJECTIVE: This study compares the effectiveness of a neuromuscular electrostimulation device (geko T-1; Firstkind Ltd, High Wycombe, UK) in enhancing lower limb blood perfusion with two leading intermittent pneumatic compression (IPC) devices, the Huntleigh Flowtron Universal (Huntleigh Healthcare Ltd, Cardiff, UK) and the Kendall SCD Express (Covidien plc, Dublin, Ireland). The subjects' tolerance of the devices was also compared. METHODS: Ten healthy subjects were recruited. The devices were fitted bilaterally, in a sequential manner, for 30 minutes. Ultrasound and laser Doppler fluxmetry assessments were performed. RESULTS: The geko T-1 device was superior to both IPC devices in increasing both venous and arterial blood volume flow by ~30% (95% confidence interval [CI], 23.7%-82.4%; P <= .001). The geko T-1 increased arterial blood velocity by 24% (95% CI, 9.7%-24.5%; P <= .001). A substantial increase in the total microcirculatory blood velocity by ~370% (95% CI, 13.5%-39.7%) was reported after the use of the geko T-1 (P <= .001). With use of the visual analog scale, no significant differences in discomfort were found between the geko T-1 device and the IPC devices (P >.05). CONCLUSIONS: The geko T-1 device is more effective than the IPC devices in increasing venous, arterial, and microcirculatory blood velocity. The devices studied were safe and well tolerated by healthy subjects. PMID- 26993183 TI - Discussion. PMID- 26993182 TI - Complications of indwelling retrievable versus permanent inferior vena cava filters. AB - OBJECTIVE: Retrievable inferior vena cava (IVC) filters are appealing because they are designed for either retrieval or long-term use. However, the long-term safety of indwelling retrievable compared with permanent filters is largely unknown. This study was undertaken to compare complication rates and types associated with indwelling retrievable and permanent filters. METHODS: A retrospective review identified 1234 IVC filters (449 retrievable, 785 permanent) placed in 1225 patients from 2005 to 2010. Patients with retrievable filters removed electively were excluded, yielding 383 patients in whom retrievable filters were left in place. These patients with indwelling retrievable filters were compared with those with permanent filters with respect to demographics, comorbidities, survival, and complication rate and type. Differences in patient characteristics were tested with chi(2), Fisher exact, and Wilcox rank-sum tests. Logistic regression was used to identify predictors of complications. Because there were differences in the characteristics of the patients with indwelling retrievable filters and permanent filters, an additional propensity score analysis was performed yielding 319 patients in each group. RESULTS: Patients with indwelling retrievable filters were younger than those with permanent filters (mean age, 62 vs 75 years; P < .0001). Patients with indwelling retrievable filters had significantly more complications than those with permanent filters (9% vs 3.0%; P < .0001) after mean follow-up of 20 months (range, 0-86 months). Filter complications were categorized as thrombotic, device related, or systemic. While the most common complication type with both indwelling retrievable and permanent filters was thrombotic (4.4% vs 2.2%; P = NS), device-related complications were significantly more common with indwelling retrievable filters compared with permanent filters (3% vs 0.5%; P < .006). Propensity score analysis demonstrated that even in the matched groups, indwelling retrievable filters were associated with significantly more complications than permanent filters (9.1% vs 3.5%; P = .0035). CONCLUSIONS: Indwelling retrievable IVC filters were associated with significantly higher complication rates than permanent filters. Both thrombotic and device-related complications were more common with retrievable filters. Long-term use of retrievable filters should be avoided, especially considering the younger population in whom they are placed. PMID- 26993184 TI - Penetration of the inferior vena cava and adjacent organs after filter placement is associated with retrievable filter type and length of time in place. AB - OBJECTIVE: Concern over local complications of inferior vena cava (IVC) filters exists, but little long-term data are available. Referrals for filter penetrations on computed tomography (CT) have increased with no standards for management. We reviewed postfilter CT findings in our institution. METHODS: All patients receiving IVC filters between January 1, 2006 and December 31, 2009 with a postfilter CT were reviewed. Penetration was graded with a previously published scale. Filter indication, type, and subsequent encounters for abdominal or back pain were recorded. RESULTS: A total of 591 patients had a filter during the study period. Of these, 262 had an adequate postfilter CT, comprising the study group. Indications were prophylaxis in 16.4% and venous thromboembolism in 83.6%. Of filters placed for venous thromboembolism, indications were absolute (inability/failure of anticoagulation) in 44.7% and relative in 55.3%. Retrievable filters made up 92.7% of the filters, and 7.3% were permanent type. Of the retrievable filters, 1.6% were retrieved. One hundred twenty (45.8%) filters had grade 2 or 3 penetration. Another 38.2% (100) had struts immediately adjacent to the external aspect of the IVC, which may represent tenting of the cava. Grade 2 or 3 penetration occurred in 49.0% of retrievable filters but only 5.3% of permanent filters (P = .0001). Grade 2 or 3 penetration occurred in 18.2% of filters less than 30 days old but in 57.3% of filters 30 days old or older (P < .0001). Thirty-two patients had subsequent encounters for abdominal or back pain, but none was conclusively related to penetration. CONCLUSIONS: A majority of filters were placed for prophylaxis or relative indications and were retrievable type. Retrieval rate was low. Penetration of the IVC and adjacent organs was common and associated with retrievable type and length of time in place. It is unclear if most penetrations cause problems. Monitoring of penetrations with CT may be important to understand the natural history of this condition. PMID- 26993185 TI - The effect of single phlebectomies of a large varicose tributary on great saphenous vein reflux. AB - OBJECTIVE: Phlebectomy of varicose tributaries is usually considered an additional treatment after or during saphenous ablation. As phlebectomies alone affect the hemodynamics of the venous system, this treatment can be effective as primary intervention in selected patients. The objective of this study was to analyze hemodynamic, clinical, and patient-reported outcomes after phlebectomies in a prospective multicenter study to determine predictors for treatment success, that is, restoration of great saphenous vein (GSV) competence. METHODS: Patients with symptomatic GSV and tributary incompetence (reflux > 0.5 second) at the level of the thigh were included. Duplex ultrasound (DUS) was used to assess GSV and tributary characteristics, and a reflux elimination test was performed. Three and 12 months after phlebectomy of the tributary, reflux and GSV diameter were evaluated with DUS. Clinical outcome measures were C class of the Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification and Venous Clinical Severity Score; patients' reported outcome was determined by the Aberdeen Varicose Vein Questionnaire. To evaluate differences between the success and failure groups, baseline DUS characteristics, Venous Clinical Severity Score, CEAP class, and Aberdeen Varicose Vein Questionnaire score were compared. Multivariable logistic regression including all clinically relevant variables following a backward variable elimination process was used to determine predictors for success. The model was internally validated by 1000 bootstrap samples. RESULTS: The study included 94 patients (65 women, 29 men) with a mean age of 53 years. The majority had C2 or C3 disease. One year after treatment, GSV reflux had disappeared in 50% of patients (P < .01), and GSV diameter had decreased significantly (P < .01). Clinical outcome and Aberdeen Varicose Vein Questionnaire score improved significantly (P < .01) and symptoms had disappeared in 66%. Of 47 patients with persisting GSV incompetence, 15 did not receive additional treatment because they were asymptomatic. Independent predictors for success were low C class of the CEAP classification, low number of refluxing GSV segments, small diameter of the GSV above the tributary, and positive reflux elimination test result (P < .0001). The reflux elimination test appeared to be an important independent predictor, with >65% chance of success when the result was positive. CONCLUSIONS: At 1-year follow-up, treatment with single phlebectomies of a large tributary was effective to abolish GSV reflux in 50% of patients and to free 66% of patients from symptoms. Patients with limited disease progression and mild DUS alterations are most likely to benefit from this approach. PMID- 26993186 TI - Biomechanical comparison between mono-, bi-, and tricuspid valve architectures. AB - BACKGROUND: An understanding of the relationship between venous valve architecture and associated fluid and solid mechanical forces will undoubtedly advance prosthesis design and treatments. The objective of the current study was to compare three valve architectures (mono-, bi-, and tricuspid) and the implications of these designs on the fluid and solid mechanics of the valve leaflets. The hypothesis is that the bi-cuspid valve has the lowest mechanical cost, defined as the ratio of leaflet wall stress and fluid wall shear stress (WSS), for the venous environment as compared with mono- and tricuspid valves. METHODS: To address this hypothesis, fully coupled, two-way fluid-structure interaction computational models were developed and simulated for the three types of valves. RESULTS: The numerical simulations showed that the mean fluid WSS of the bicuspid valve was generally higher than the tri-cuspid valve, which was further higher than the monocuspid valve. The mean leaflet wall stress of the bicuspid valve was lower than the tricuspid valve, which was further lower than the monocuspid valve. Therefore, the mechanical cost, which was defined as solid wall stress/fluid WSS, of the bicuspid valve was the lowest. CONCLUSIONS: The lower mechanical cost may be a reason why the bicuspid valve is the dominant design in the venous system. This knowledge provides guidance for the design of novel venous prosthetic valves and may shed light on venous valve disease when the architecture of the valve is altered. PMID- 26993187 TI - Venous cystic adventitial disease of the common femoral vein. AB - Venous adventitial cystic disease is a rare condition with few reports previously described. We report the case of a 39-year-old female who presented with left lower extremity edema, acutely exacerbated by exercise. Imaging revealed a hypoechoic mass posterior to her left common femoral vein. Open surgical excision and evacuation was performed with resolution of symptoms within 24 hours. A review of the literature is discussed, along with presentation, diagnosis, treatment, and pathology of this intriguing condition. PMID- 26993188 TI - Chronic common femoral vein occlusion secondary to endometriosis. AB - Venous occlusion is sometimes caused by external compression due to adjacent masses. Endometriosis, the presence of functioning endometrial tissue outside the uterine cavity, is a rare cause of venous occlusion. We report a case of chronic common femoral vein occlusion due to endometrioma causing severe leg edema and groin pain that was treated with resection and venous bypass. PMID- 26993189 TI - Customized femoral vein grafts for inferior vena cava reconstruction. AB - After extended en-bloc resection of a retroperitoneal neoplasm, prosthetic grafts can efficiently replace the inferior vena cava. However, in cases of concomitant biliary or bowel surgery, there is a risk of infection, and autogenous materials typically used present with size match. We present a method of autogenous graft construction using the femoral vein for replacement of the inferior vena cava, with an alternate configuration for renal vein implantation. PMID- 26993190 TI - Left iliac vein occlusion treated with a Palma procedure. PMID- 26993191 TI - Left-sided inferior vena cava. PMID- 26993192 TI - A different way to look at varicose veins. AB - OBJECTIVE: The development of varicose veins is commonly attributed to vessel wall degeneration. The idea that varicose veins occur because of pathological processes, however, is challenged by certain observations. For example, their high prevalence (50% or greater) in many populations makes it statistically "normal" to have varicose veins; their well-established genetic predisposition raises the possibility that this high prevalence reflects a survival benefit. One way to explain this apparent contradiction is to theorize that varicose veins are produced by the same mechanism(s) that lead to the growth and remodeling of other types of blood vessels. If so, being "good" at forming varicose veins may also predispose to being "good" at forming various types of collateral blood vessels when necessary. METHODS: A selected literature review was conducted. Works chosen for review included those suggesting that: the process of varicose vein formation may share the same basic mechanisms as the formation of collateral veins, arteries, and lymphatic vessels; and clinical outcomes may be different between subjects with and without varicose veins. RESULTS: Evidence suggests that subjects who are "good" at forming varicose veins may also be "good" at forming various types of collateral vessels, and they may have better overall survival (with less cardiovascular morbidity) than those without varicose veins. CONCLUSIONS: Varicose veins may be "the price we pay" for an enhanced ability to form collateral vessels when necessary. PMID- 26993193 TI - Comparative effectiveness of surgical interventions aimed at treating underlying venous pathology in patients with chronic venous ulcer. AB - OBJECTIVE: Chronic venous ulcers (CVUs) remain the leading causes for nonhealing wounds in the lower extremities. Although multilayer compression dressing remains the treatment gold standard, there are various surgical procedures aimed at healing CVUs with little or no evidence on the efficacy of these treatment methods. We conducted a systematic review of the effects of various surgical treatments for CVUs, in terms of ulcer healing rates, complete time to heal, recurrence rates, mortality, pain, and quality of life. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register for Controlled Trials, and the Cumulative Index for Nursing and Allied Health Literature databases from January 1980 through July 2012. We included studies that compared a surgical procedure with multilayer compression therapy or another surgical procedure among patients with CVUs. We also included studies without a comparison group if they were of sufficient quality. Two independent reviewers screened titles, abstracts, and articles for eligibility. Two reviewers extracted data on study design, applicability, results, and quality. RESULTS: We identified 10,676 citations, of which 22 studies (23 publications) were included. Eight studies (six randomized controlled trials, two cohorts) compared a surgical procedure with compression. Fourteen studies evaluated different surgical interventions. Adding superficial vein ligation and stripping to compression did not improve wound-healing rate. However, the recurrence rate was 50% reduced when surgery corrected the underlying superficial venous pathology (moderate to high strength of evidence [SOE]). Adding subfascial endoscopic perforator surgery with superficial vein surgery to compression does not improve the healing rate of venous ulcers or reduce the recurrence rate except for medial and large ulcers (high SOE). The SOE was insufficient to support a conclusion about the effects of sclerotherapy when added to compression in healing CVUs. There was insufficient evidence on the surgical treatment of CVUs secondary to deep venous reflux and venous obstruction. We are unable to draw conclusions about the effects of surgical procedures on mortality, pain, and quality of life. CONCLUSIONS: Our ability to draw conclusions on most surgical techniques is limited due to poorly designed and executed studies, with no uniformity of treatment methods, follow-up or reporting, and lack of randomization. We found some evidence to suggest superficial vein ligation and stripping may reduce the risk of wound recurrence, but these surgical techniques are infrequently performed. The newer minimally invasive techniques lack evidence. Randomized controlled trials for the endovenous procedures used today for treating CVUs are needed. PMID- 26993194 TI - Hemorrhoid veins, the forgotten realm of the vascular surgeon. PMID- 26993195 TI - Use of aspirin for the prevention of lower extremity deep venous thrombosis. AB - Whereas aspirin is recommended and widely used to prevent arterial thrombosis, its role in the prevention of deep venous thrombosis is not well defined. Aspirin is well accepted, easy to manage with few risks and low cost, and thus ideal for thromboprophylaxis if evidence shows it is effective. Recent guidelines and large studies were reviewed. Recent guidelines include aspirin as an acceptable thromboprophylactic agent after hip and knee orthopedic surgery despite continued publication of underpowered and contradictory studies. Two large randomized controlled trials pooled together suggest that low-dose (100 mg) aspirin is a reasonable alternative to prevent recurrence of venous thromboembolism (VTE) in patients who have been treated for a first episode of unprovoked VTE. We suggest that the current practice using aspirin to prevent thromboembolism include cautious discussion of the benefits and risks of this agent before use in a patient until precise clarification of dosage and treatment length is available. Despite inclusion of aspirin in the guidelines for orthopedic surgery, there is little evidence to support its use for primary prevention of VTE. Until definitive unbiased trials are published, we suggest that aspirin remain a realistic option to use for secondary prevention of VTE, especially compared with the option of using no prophylaxis. PMID- 26993197 TI - Information for readers. PMID- 26993198 TI - Events of interest. PMID- 26993199 TI - Neurofilament networks: Salt-responsive hydrogels with sidearm-dependent phase behavior. AB - BACKGROUND: Neurofilaments (NFs) - the neuron-specific intermediate filament proteins - are assembled into 10nm wide filaments in a tightly controlled ratio of three different monomer types: NF-Low (NF-L), NF-Medium (NF-M), and NF-High (NF-H). Previous work on reconstituted bovine NF hydrogels has shown the dependence of network properties, including filament alignment and spacing, on the subunit composition. METHODS: We use polarized optical microscopy and SAXS to explore the full salt-dependent phase behavior of reconstituted bovine NF networks as a function of various binary and ternary subunit ratios. RESULTS: We observe three salt-induced liquid crystalline phases: the liquid-ordered B(G) and N(G) phases, and the disordered I(G) phase. We note the emergent sidearm roles, particularly that of NF-H in driving the parallel to cross-filament transition, and the counter-role of NF-M in suppressing the I(G) phase. CONCLUSIONS: In copolymers of NF-LH, NF-H shifts the I(G) to N(G) transition to nearer physiological salt concentrations, as compared to NF-M in copolymers of NF-LM. For ternary mixtures, the role of NF-H is modulated by the ratio of NF-M, where beneath 10wt.% NF-M, NF-H drives the transition to the disordered phase, and above which NF-H increases interfilament spacing. GENERAL SIGNIFICANCE: Understanding the role of individual subunits in regulating the network structure will enable us to understand the mechanisms that drive the dysfunction of these networks, as observed in diseased conditions. PMID- 26993200 TI - Beyond PM2.5: The role of ultrafine particles on adverse health effects of air pollution. AB - BACKGROUND: Air pollution constitutes the major threat to human health, whereas their adverse impacts and underlying mechanisms of different particular matters are not clearly defined. SCOPE OF REVIEW: Ultrafine particles (UFPs) are high related to the anthropogenic emission sources, i.e. combustion engines and power plants. Their composition, source, typical characters, oxidative effects, potential exposure routes and health risks were thoroughly reviewed. MAJOR CONCLUSIONS: UFPs play a major role in adverse impacts on human health and require further investigations in future toxicological research of air pollution. GENERAL SIGNIFICANCE: Unlike PM2.5, UFPs may have much more impacts on human health considering loads of evidences emerging from particulate matters and nanotoxicology research fields. The knowledge of nanotoxicology contributes to the understanding of toxicity mechanisms of airborne UFPs in air pollution. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. PMID- 26993201 TI - Microbial assisted High Impact Polystyrene (HIPS) degradation. AB - The efficacy of newly isolated Pseudomonas and Bacillus strains to degrade brominated High Impact Polystyrene (HIPS) was investigated. Viability of these cultures while using e-plastic as sole carbon source was validated through Triphenyl Tetrazolium Chloride (TTC). Four days incubation of HIPS emulsion with Bacillus spp. showed 94% reduction in turbidity and was 97% with Pseudomonas spp. Confirmation of degradation was concluded by HPLC, NMR, FTIR, TGA and weight loss analysis. NMR spectra of the degraded film revealed the formation of aliphatic carbon chain with bromine and its release. FTIR analysis of the samples showed a reduction in CH, CO and CN groups. Surface changes in the brominated HIPS film was visualized through SEM analysis. Degradation with Bacillus spp showed a weight loss of 23% (w/w) of HIPS film in 30days. PMID- 26993202 TI - The development and validation of a meta-tool for quality appraisal of public health evidence: Meta Quality Appraisal Tool (MetaQAT). AB - OBJECTIVES: Most quality appraisal tools were developed for clinical medicine and tend to be study-specific with a strong emphasis on risk of bias. In order to be more relevant to public health, an appropriate quality appraisal tool needs to be less reliant on the evidence hierarchy and consider practice applicability. Given the broad range of study designs used in public health, the objective of this study was to develop and validate a meta-tool that combines public health-focused principles of appraisal coupled with a set of design-specific companion tools. STUDY DESIGN: Several design methods were used to develop and validate the tool including literature review, synthesis, and validation with a reference standard. METHODS: A search of critical appraisal tools relevant to public health was conducted; core concepts were collated. The resulting framework was piloted during three feedback sessions with public health practitioners. Following subsequent revisions, the final meta-tool, the Meta Quality Appraisal Tool (MetaQAT), was then validated through a content analysis of appraisals conducted by two groups of experienced public health researchers (MetaQAT vs generic appraisal form). RESULTS: The MetaQAT framework consists of four domains: relevancy, reliability, validity, and applicability. In addition, a companion tool was assembled from existing critical appraisal tools to provide study design specific guidance on validity appraisal. Content analysis showed similar methodological and generalizability concerns were raised by both groups; however, the MetaQAT appraisers commented more extensively on applicability to public health practice. CONCLUSIONS: Critical appraisal tools designed for clinical medicine have limitations for use in the context of public health. The meta-tool structure of the MetaQAT allows for rigorous appraisal, while allowing users to simultaneously appraise the multitude of study designs relevant to public health research and assess non-standard domains, such as applicability. PMID- 26993206 TI - Mouse Osteoblasts Play a Crucial Role in the Immune System. AB - This commentary highlights the article by Tu et al describing mechanisms in immune-mediated arthritis that may propel strategies to treat diseases involving the bone and immune system. PMID- 26993209 TI - Impact of aerobic fitness on cerebral blood flow and cerebral vascular responsiveness to CO2 in young and older men. AB - We sought to test the hypothesis that brain blood flow and cerebral vascular responsiveness to carbon dioxide (CVRCO2 ) are greater in aerobically trained young and old individuals compared to their untrained counterparts. In 11 young trained {[23 (20-26) years] [mean (95% confidence interval)]}, 10 young untrained [25 (22-28) years], 8 older trained [65 (61-69) years], and 9 older untrained [67 (64-71) years] healthy individuals, Doppler ultrasound of the internal carotid (ICA) and vertebral (VA) artery blood flow were determined, along with middle cerebral artery mean flow velocity (MCA Vmean ). Bilateral ICA blood flow was higher in trained individuals when compared to untrained (~31%, P < 0.05), but was not influenced by age. VA blood flow was not affected by age or cardiorespiratory fitness. MCA Vmean was reduced with age [59.5 (55.0-64.1) cm/s young vs 43.6 (38.4-48.9) cm/s old, P < 0.05] with no significant effect of training observed. MCA CVRCO2 were not significantly affected by either age or training status, while ICA CVRCO2 tended to be elevated in the old trained group. These findings indicate that endurance training enhances bilateral ICA but not VA blood flow in both young and older individuals. PMID- 26993208 TI - Guidelines for the Reduction of Cardiovascular Disease in Women. AB - Since 1984, more women than men have died each year from cardiovascular disease. Various organizations, such as the American Heart Association and the American College of Cardiology, have published prevention guidelines for heart disease and stroke that may improve care for women. In this article, we review these guidelines, the results of new studies on emerging risk factors, and new approaches for reducing cardiovascular disease in women. PMID- 26993207 TI - Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes. AB - Recently, The Cancer Genome Atlas data revealed four molecular subtypes of high grade serous ovarian carcinoma (HGSOC) exhibiting distinct prognoses. We developed four novel HGSOC histopathological subtypes by focusing on tumor microenvironment: mesenchymal transition, defined by a remarkable desmoplastic reaction; immune reactive by lymphocytes infiltrating the tumor; solid and proliferative by a solid growth pattern; and papilloglandular by a papillary architecture. Unsupervised hierarchical clustering revealed four clusters correlated with histopathological subtypes in both Kyoto and Niigata HGSOC transcriptome data sets (P < 0.001). Gene set enrichment analysis revealed pathways enriched in our histopathological classification significantly overlapped with the four molecular subtypes: mesenchymal, immunoreactive, proliferative, and differentiated (P < 0.0001, respectively). In 132 HGSOC cases, progression-free survival and overall survival were best in the immune reactive, whereas overall survival was worst in the mesenchymal transition (P < 0.001, respectively), findings reproduced in 89 validation cases (P < 0.05, respectively). The CLOVAR_MES_UP single-sample gene set enrichment analysis scores representing the mesenchymal molecular subtype were higher in paclitaxel responders than nonresponders (P = 0.002) in the GSE15622 data set. Taxane containing regimens improved survival of cases with high MES_UP scores compared with nontaxane regimens (P < 0.001) in the GSE9891 data set. Our novel histopathological classification of HGSOC correlates with distinct prognostic transcriptome subtypes. The mesenchymal transition subtype might be particularly sensitive to taxane. PMID- 26993210 TI - Biological in situ characterization of polymeric microbubble contrast agents. AB - Polymeric microbubbles (MBs) are gas filled particles composed of a thin stabilized polymer shell that have been recently developed as valid contrast agents for the combined use of ultrasonography (US), magnetic resonance imaging (MRI) and single photon emission computer tomography (SPECT) imaging. Due to their buoyancy, the commonly available approaches to study their behaviour in complex media are not easily applicable and their use in modern medicine requires such behaviour to be fully elucidated. Here we have used for the first time flow cytometry as a new high throughput approach that allows characterisation of the MB dispersion, prior to and after exposure in different biological media and we have additionally developed a method that allows characterisation of the strongly bound proteins adsorbed on the MBs, to fully predict their biological behaviour in biological milieu. PMID- 26993211 TI - A signature of 12 microRNAs is robustly associated with growth rate in a variety of CHO cell lines. AB - As Chinese Hamster Ovary (CHO) cells are the cell line of choice for the production of human-like recombinant proteins, there is interest in genetic optimization of host cell lines to overcome certain limitations in their growth rate and protein secretion. At the same time, a detailed understanding of these processes could be used to advantage by identification of marker transcripts that characterize states of performance. In this context, microRNAs (miRNAs) that exhibit a robust correlation to the growth rate of CHO cells were determined by analyzing miRNA expression profiles in a comprehensive collection of 46 samples including CHO-K1, CHO-S and CHO-DUKXB11, which were adapted to various culture conditions, and analyzed in different growth stages using microarrays. By applying Spearman or Pearson correlation coefficient criteria of>|0.6|, miRNAs with high correlation to the overall growth, or growth rates observed in exponential, serum-free, and serum-free exponential phase were identified. An overlap of twelve miRNAs common for all sample sets was revealed, with nine positively and three negatively correlating miRNAs. The here identified panel of miRNAs can help to understand growth regulation in CHO cells and contains putative engineering targets as well as biomarkers for cell lines with advantageous growth characteristics. PMID- 26993212 TI - Adhesive systems under fissure sealants: yes or no?: A systematic review and meta analysis. AB - BACKGROUND: The authors of this systematic review and meta-analysis had 2 aims: to evaluate fissure sealant retention with and without the use of an adhesive system and to compare fissure sealant retention using etch-and-rinse adhesive systems versus self-etching adhesive systems. TYPES OF STUDIES REVIEWED: The authors conducted a literature search (all articles published through November 1, 2015) to identify studies for inclusion in this systematic review. They assessed the quality of the evidence provided using the modified Jadad scale and performed meta-analyses using a random-effects model. RESULTS: The authors considered 12 studies that met the inclusion criteria for the systematic review. In addition, they used 5 of 9 studies related to the first part of the study and 3 of 4 studies related to the second part of the study that met the inclusion criteria for meta-analysis. In the analysis of the first part of the systematic review, the authors found that adhesive systems had a significant positive effect on fissure sealant (odds ratio, 3.294; 95% confidence interval, 1.292-8.401; P = .013). In the analysis of the second part of the systematic review, the authors found that etch-and-rinse adhesives were superior to self-etching adhesives in the fissure sealant procedure (odds ratio, 14.569; 95% confidence interval, 2.616 81.131; P = .002). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The use of adhesive systems beneath fissure sealants can increase the retention of fissure sealants. Also, when adhesive systems are used with fissure sealants, etch-and-rinse systems are preferable. PMID- 26993213 TI - 100 Million Views of Electronic Cigarette YouTube Videos and Counting: Quantification, Content Evaluation, and Engagement Levels of Videos. AB - BACKGROUND: The video-sharing website, YouTube, has become an important avenue for product marketing, including tobacco products. It may also serve as an important medium for promoting electronic cigarettes, which have rapidly increased in popularity and are heavily marketed online. While a few studies have examined a limited subset of tobacco-related videos on YouTube, none has explored e-cigarette videos' overall presence on the platform. OBJECTIVE: To quantify e cigarette-related videos on YouTube, assess their content, and characterize levels of engagement with those videos. Understanding promotion and discussion of e-cigarettes on YouTube may help clarify the platform's impact on consumer attitudes and behaviors and inform regulations. METHODS: Using an automated crawling procedure and keyword rules, e-cigarette-related videos posted on YouTube and their associated metadata were collected between July 1, 2012, and June 30, 2013. Metadata were analyzed to describe posting and viewing time trends, number of views, comments, and ratings. Metadata were content coded for mentions of health, safety, smoking cessation, promotional offers, Web addresses, product types, top-selling brands, or names of celebrity endorsers. RESULTS: As of June 30, 2013, approximately 28,000 videos related to e-cigarettes were captured. Videos were posted by approximately 10,000 unique YouTube accounts, viewed more than 100 million times, rated over 380,000 times, and commented on more than 280,000 times. More than 2200 new videos were being uploaded every month by June 2013. The top 1% of most-viewed videos accounted for 44% of total views. Text fields for the majority of videos mentioned websites (70.11%); many referenced health (13.63%), safety (10.12%), smoking cessation (9.22%), or top e cigarette brands (33.39%). The number of e-cigarette-related YouTube videos was projected to exceed 65,000 by the end of 2014, with approximately 190 million views. CONCLUSIONS: YouTube is a major information-sharing platform for electronic cigarettes. YouTube appears to be used unevenly for promotional purposes by e-cigarette brands, and our analyses indicated a high level of user engagement with a small subset of content. There is evidence that YouTube videos promote e-cigarettes as cigarette smoking cessation tools. Presence and reach of e-cigarette videos on YouTube warrants attention from public health professionals and policymakers. PMID- 26993215 TI - Extracapsular Extension in the Sentinel Lymph Node: Guidelines for Therapy. PMID- 26993214 TI - Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury. AB - Using magnetic resonance imaging (MRI) and an animal model of traumatic brain injury (TBI), we investigated the capacity and sensitivity of diffusion-derived measures, fractional anisotropy (FA), and diffusion entropy, to longitudinally identify structural plasticity in the injured brain in response to the transplantation of human bone marrow stromal cells (hMSCs). Male Wistar rats (300 350g, n = 30) were subjected to controlled cortical impact TBI. At 6 h or 1 week post-injury, these rats were intravenously injected with 1 mL of saline (at 6 h or 1 week, n = 5/group) or with hMSCs in suspension (~3 * 106 hMSCs, at 6 h or 1 week, n = 10/group). In vivo MRI measurements and sensorimotor function estimates were performed on all animals pre-injury, 1 day post-injury, and weekly for 3 weeks post-injury. Bielschowsky's silver and Luxol fast blue staining were used to reveal the axon and myelin status, respectively, with and without cell treatment after TBI. Based on image data and histological observation, regions of interest encompassing the structural alterations were made and the values of FA and entropy were monitored in these specific brain regions. Our data demonstrate that administration of hMSCs after TBI leads to enhanced white matter reorganization particularly along the boundary of contusional lesion, which can be identified by both FA and entropy. Compared with the therapy performed at 1 week post-TBI, cell intervention executed at 6 h expedites the brain remodeling process and results in an earlier functional recovery. Although FA and entropy present a similar capacity to dynamically detect the microstructural changes in the tissue regions with predominant orientation of fiber tracts, entropy exhibits a sensitivity superior to that of FA, in probing the structural alterations in the tissue areas with complex fiber patterns. PMID- 26993217 TI - Embryonic exposures of lithium and homocysteine and folate protection affect lipid metabolism during mouse cardiogenesis and placentation. AB - Embryonic exposures can increase the risk of congenital cardiac birth defects and adult disease. The present study identifies the predominant pathways modulated by an acute embryonic mouse exposure during gastrulation to lithium or homocysteine that induces cardiac defects. High dose periconceptional folate supplementation normalized development. Microarray bioinformatic analysis of gene expression demonstrated that primarily lipid metabolism is altered after the acute exposures. The lipid-related modulation demonstrated a gender bias with male embryos showing greater number of lipid-related Gene Ontology biological processes altered than in female embryos. RT-PCR analysis demonstrated significant change of the fatty acid oxidation gene Acadm with homocysteine exposure primarily in male embryos than in female. The perturbations resulting from the exposures resulted in growth-restricted placentas with disorganized cellular lipid droplet distribution indicating lipids have a critical role in cardiac-placental abnormal development. High folate supplementation protected normal heart-placental function, gene expression and lipid localization. PMID- 26993216 TI - Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients With an Initial Diagnosis of Cytology-Proven Lymph Node-Positive Breast Cancer. AB - BACKGROUND: Sentinel lymph node biopsy (SNB) is the standard treatment of node negative breast cancer; however, whether SNB should be performed for patients with node-positive disease before neoadjuvant chemotherapy (NAC) is controversial. We evaluated the accuracy of SNB after NAC in patients with breast cancer with nodal metastasis before chemotherapy to determine the false-negative rate (FNR) and detection rate for SNB. PATIENTS AND METHODS: In the present multicenter prospective study performed from September 2011 to April 2013, 143 patients with breast cancer and positive axillary nodes, proved by fine needle aspiration cytology at the initial diagnosis (stage T1-T3N1M0), were enrolled. All patients underwent breast surgery with SNB and complete axillary lymph node dissection. RESULTS: After NAC, the pathologic complete nodal response rate was 52.4%. The sentinel lymph node could be identified in 130 cases (90.9%); the FNR was 16.0% (13 of 81). The FNR of each clinical subtype was 42.1% (8 of 19) for the estrogen receptor-positive and human epithelial growth factor 2 (HER2) negative (luminal type), 16.7% (2 of 12) for ER-positive and HER2-positive (luminal-HER2 type), 3.2% (1 of 31) for HER2-positive (HER2-enriched type), and 10.5% (2 of 19) for ER-negative and HER2-negative (triple-negative breast cancer; P = .003). The FNR was significantly greater in the luminal than in the nonluminal type (odds ratio, 9.91; 95% confidence interval, 6.77-14.52). CONCLUSION: SNB after NAC in patients with initially node-positive breast cancer was technically feasible but should not be recommended for the luminal subtype. However, the tumor subtype can guide patient selection, and axillary lymph node dissection could be omitted for the luminal-HER2, HER2-enriched, and triple negative breast cancer subtypes. PMID- 26993218 TI - Loop diuretics are most appropriate for hypertension treatment in chronic kidney disease. PMID- 26993219 TI - Treating Immunodeficiency through HSC Gene Therapy. AB - Haematopoietic stem cell (HSC) gene therapy has been successfully employed as a therapeutic option to treat specific inherited immune deficiencies, including severe combined immune deficiencies (SCID) over the past two decades. Initial clinical trials using first-generation gamma-retroviral vectors to transfer corrective DNA demonstrated clinical benefit for patients, but were associated with leukemogenesis in a number of cases. Safer vectors have since been developed, affording comparable efficacy with an improved biosafety profile. These vectors are now in Phase I/II clinical trials for a number of immune disorders with more preclinical studies underway. Targeted gene editing allowing precise DNA correction via platforms such as ZFNs, TALENs and CRISPR/Cas9 may now offer promising strategies to improve the safety and efficacy of gene therapy in the future. PMID- 26993222 TI - When the endothelium scores an own goal: endothelial cells actively augment metastatic extravasation through endothelial-mesenchymal transition. AB - Endothelial-mesenchymal transition (EndMT) is an important mechanism during organ development and in certain pathological conditions. For example, EndMT contributes to myofibroblast formation during organ fibrosis, and it has been identified as an important source of cancer-associated fibroblasts, facilitating tumor progression. Recently, EndMT was proposed to modulate endothelial function during intravasation and extravasation of metastatic tumor cells. Evidence suggests that endothelial cells are not passive actors during transendothelial migration (TEM) of cancer cells, as there are profound changes in endothelial junctional protein expression, signaling, permeability, and contractility. This review describes these alterations in endothelial characteristics during TEM of metastatic tumor cells and discusses them in the context of EndMT. EndMT could play an important role during metastatic intravasation and extravasation, a novel hypothesis that may lead to new therapeutic approaches to tackle metastatic disease. PMID- 26993221 TI - Antiarrhythmic effect of growth factor-supplemented cardiac progenitor cells in chronic infarcted heart. AB - c-Kit(pos) cardiac progenitor cells (CPCs) represent a successful approach in healing the infarcted heart and rescuing its mechanical function, but electrophysiological consequences are uncertain. CPC mobilization promoted by hepatocyte growth factor (HGF) and IGF-1 improved electrogenesis in myocardial infarction (MI). We hypothesized that locally delivered CPCs supplemented with HGF + IGF-1 (GFs) can concur in ameliorating electrical stability of the regenerated heart. Adult male Wistar rats (139 rats) with 4-wk-old MI or sham conditions were randomized to receive intramyocardial injection of GFs, CPCs, CPCs + GFs, or vehicle (V). Enhanced green fluorescent protein-tagged CPCs were used for cell tracking. Vulnerability to stress-induced arrhythmia was assessed by telemetry-ECG. Basic cardiac electrophysiological properties were examined by epicardial multiple-lead recording. Hemodynamic function was measured invasively. Hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. Compared with V and at variance with individual CPCs, CPCs + GFs approximately halved arrhythmias in all animals, restoring cardiac anisotropy toward sham values. GFs alone reduced arrhythmias by less than CPCs + GFs, prolonging ventricular refractoriness without affecting conduction velocity. Concomitantly, CPCs + GFs reactivated the expression levels of Connexin-43 and Connexin-40 as well as channel proteins of key depolarizing and repolarizing ion currents differently than sole GFs. Mechanical function and anatomical remodeling were equally improved by all regenerative treatments, thus exhibiting a divergent behavior relative to electrical aspects. Conclusively, we provided evidence of distinctive antiarrhythmic action of locally injected GF-supplemented CPCs, likely attributable to retrieval of Connexin-43, Connexin-40, and Cav1.2 expression, favoring intercellular coupling and spread of excitation in mended heart. PMID- 26993220 TI - An Immunological Perspective on Neonatal Sepsis. AB - Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more integrated understanding of the developing human immune system in the context of its microbial environment. We review these recent findings, focusing on how in human newborns incomplete maturation of the immune system before a full term of gestation impacts on their vulnerability to infection. We also discuss some of the clinical implications of this research in guiding the design of more accurate age-adapted diagnostic and preventive strategies for neonatal sepsis. PMID- 26993223 TI - Hydrogen sulfide depletion contributes to microvascular remodeling in obesity. AB - Structural remodeling of the microvasculature occurs during obesity. Based on observations that impaired H2S signaling is associated with cardiovascular pathologies, the current study was designed to test the hypothesis that altered H2S homeostasis is involved in driving the remodeling process in a diet-induced mouse model of obesity. The structural and passive mechanical properties of mesenteric resistance arterioles isolated from 30-wk-old lean and obese mice were assessed using pressure myography, and vessel H2S levels were quantified using the H2S indicator sulfidefluor 7-AM. Remodeling gene expression was assessed using quantitative RT-PCR, and histological staining was used to quantify vessel collagen and elastin. Obesity was found to be associated with decreased vessel H2S concentration, inward hypertrophic remodeling, altered collagen-to-elastin ratio, and reduced vessel stiffness. In addition, mRNA levels of fibronectin, collagen types I and III, matrix metalloproteinases 2 and 9, and tissue inhibitor of metalloproteinase 1 were increased and elastin was decreased by obesity. Evidence that decreased H2S was responsible for the genetic changes was provided by experiments in which H2S levels were manipulated, either by inhibition of the H2S-generating enzyme cystathionine gamma-lyase with dl-propargylglycine or by incubation with the H2S donor GYY4137. These data suggest that, during obesity, depletion of H2S is involved in orchestrating the genetic changes underpinning inward hypertrophic remodeling in the microvasculature. PMID- 26993225 TI - Myocardial reverse remodeling: how far can we rewind? AB - Heart failure (HF) is a systemic disease that can be divided into HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). HFpEF accounts for over 50% of all HF patients and is typically associated with high prevalence of several comorbidities, including hypertension, diabetes mellitus, pulmonary hypertension, obesity, and atrial fibrillation. Myocardial remodeling occurs both in HFrEF and HFpEF and it involves changes in cardiac structure, myocardial composition, and myocyte deformation and multiple biochemical and molecular alterations that impact heart function and its reserve capacity. Understanding the features of myocardial remodeling has become a major objective for limiting or reversing its progression, the latter known as reverse remodeling (RR). Research on HFrEF RR process is broader and has delivered effective therapeutic strategies, which have been employed for some decades. However, the RR process in HFpEF is less clear partly due to the lack of information on HFpEF pathophysiology and to the long list of failed standard HF therapeutics strategies in these patient's outcomes. Nevertheless, new proteins, protein protein interactions, and signaling pathways are being explored as potential new targets for HFpEF remodeling and RR. Here, we review recent translational and clinical research in HFpEF myocardial remodeling to provide an overview on the most important features of RR, comparing HFpEF with HFrEF conditions. PMID- 26993224 TI - Effects of estrogen on cerebrovascular function: age-dependent shifts from beneficial to detrimental in small cerebral arteries of the rat. AB - In the present study, interactions of age and estrogen in the modulation of cerebrovascular function were examined in small arteries <150 MUM. The hypothesis tested was that age enhances deleterious effects of exogenous estrogen by augmenting constrictor prostanoid (CP)-potentiated reactivity of the female (F) cerebrovasculature. F Sprague-Dawley rats approximating key stages of "hormonal aging" in humans were studied: perimenopausal (mature multi-gravid, MA, cyclic, 5 6 mo of age) and postmenopausal (reproductively senescent, RS, acyclic 10-12 mo of age). Rats underwent bilateral ovariectomy and were given estrogen replacement therapy (E) or placebo (O) for 14-21 days. Vasopressin reactivity (VP, 10(-12) 10(-7) M) was measured in pressurized middle cerebral artery segments, alone or in the presence of COX-1- (SC560, 1 MUM) or COX-2- (NS398, 10 MUM) selective inhibitors. VP-stimulated release of prostacyclin (PGI2) and thromboxane (TXA2) were assessed by radioimmunoassay of 6-keto-PGF1alpha and TXB2 (stable metabolites). VP-induced vasoconstriction was attenuated in ovariectomized + estrogen-replaced, multigravid adult rats (5-6 mo; MAE) but potentiated in older ovariectomized + estrogen-replaced, reproductively senescent rats (12-14 mo; RSE). SC560 and NS398 reduced reactivity similarly in ovariectomized multigravid adult rats (5-6 mo; MAO) and ovariectomized reproductively senescent rat (12-14 mo; RSO). In MAE, reactivity to VP was reduced to a greater extent by SC560 than by NS398; however, in RSE, this effect was reversed. VP-stimulated PGI2 was increased by estrogen, yet reduced by age. VP-stimulated TXA2 was increased by estrogen and age in RSE but did not differ in MAO and RSO. Taken together, these data reveal that the vascular effects of estrogen are distinctly age-dependent in F rats. In younger MA, beneficial and protective effects of estrogen are evident (decreased vasoconstriction, increased dilator prostanoid function). Conversely, in older RS, detrimental effects of estrogen begin to be manifested (enhanced vasoconstriction and CP function). These findings may lead to age-specific estrogen replacement therapies that maximize beneficial and minimize detrimental effects of this hormone on small cerebral arteries that regulate blood flow. PMID- 26993226 TI - Tissue inhibitor of metalloproteinases 3-dependent microvascular endothelial cell barrier function is disrupted under septic conditions. AB - Sepsis is associated with dysfunction of microvascular endothelial cells (MVEC) leading to tissue edema and multiple organ dysfunction. Metalloproteinases can regulate MVEC function through processing of cell surface proteins, and tissue inhibitor of metalloproteinases 3 (TIMP3) regulates metalloproteinase activity in the lung following injury. We hypothesize that TIMP3 promotes normal pulmonary MVEC barrier function through inhibition of metalloproteinase activity. Naive Timp3(-/-) mice had significantly higher basal pulmonary microvascular Evans blue (EB) dye-labeled albumin leak vs. wild-type (WT) mice. Additionally, cecal ligation/perforation (CLP)-induced sepsis significantly increased pulmonary microvascular EB-labeled albumin leak in WT but not Timp3(-/-) mice. Similarly, PBS-treated isolated MVEC monolayers from Timp3(-/-) mice displayed permeability barrier dysfunction vs. WT MVEC, evidenced by lower transendothelial electrical resistance and greater trans-MVEC flux of fluorescein-dextran and EB-albumin. Cytomix (equimolar interferon gamma, tumor necrosis factor alpha, and interleukin 1beta) treatment of WT MVEC induced significant barrier dysfunction (by all three methods), and was associated with a time-dependent decrease in TIMP3 mRNA and protein levels. Additionally, basal Timp3(-/-) MVEC barrier dysfunction was associated with disrupted MVEC surface VE-cadherin localization, and both barrier dysfunction and VE-cadherin localization were rescued by treatment with GM6001, a synthetic metalloproteinase inhibitor. TIMP3 promotes normal MVEC barrier function, at least partially, through inhibition of metalloproteinase-dependent disruption of adherens junctions, and septic downregulation of TIMP3 may contribute to septic MVEC barrier dysfunction. PMID- 26993227 TI - Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes. AB - Hypothermia/rewarming (H/R) is poorly tolerated by the myocardium; however, the underlying intracellular basis of H/R-induced cardiac dysfunction remains elusive. We hypothesized that in cardiomyocytes, H/R disrupts excitation contraction coupling by reducing myofilament Ca(2+) sensitivity due to an increase in cardiac troponin I (cTnI) phosphorylation. To test this hypothesis, isolated rat cardiomyocytes (13-15 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca(2+) ([Ca(2+)]cyto) and contractile (sarcomere shortening) responses that were simultaneously measured using an IonOptix system. Cardiomyocytes were divided into two groups: 1) those exposed to hypothermia (15 degrees C for 2 h) followed by rewarming (35 degrees C; H/R); or 2) time-matched normothermic (35 degrees C) controls (CTL). Contractile dysfunction after H/R was indicated by reduced velocity and extent of sarcomere length (SL) shortening compared with time-matched controls. Throughout hypothermia, basal [Ca(2+)]cyto increased and the duration of evoked [Ca(2+)]cyto transients was prolonged. Phase-loop plots of [Ca(2+)]cyto vs. contraction were shifted rightward in cardiomyocytes during hypothermia compared with CTL, indicating a decrease in Ca(2+) sensitivity. Using Western blot, we found that H/R increases cTnI phosphorylation. These results support our overall hypothesis and suggest that H/R disrupts excitation-contraction coupling of cardiomyocytes due to increased cTnI phosphorylation and reduced Ca(2+) sensitivity. PMID- 26993228 TI - Inhibition of late Na+ current, a novel target to improve diastolic function and electrical abnormalities in Dahl salt-sensitive rats. AB - Late Na(+) current (INaL) is enhanced in myocytes of animals with chronic heart failure and patients with hypertrophic cardiomyopathy. To define the role of INaL in diastolic heart failure, the effects of GS-458967 (GS-967), a potent INaL inhibitor on mechanical and electrical abnormalities, were determined in an animal model of diastolic dysfunction. Dahl salt-sensitive (DSS) rats fed a high salt (HS) diet for 8 wk, compared with a normal salt (NS) diet, had increased left ventricular (LV) mass (1,257 +/- 96 vs. 891 +/- 34 mg) and diastolic dysfunction [isovolumic relaxation time (IVRT): 26.8 +/- 0.5 vs. 18.9 +/- 0.2 ms; early transmitral flow velocity/early mitral annulus velocity (E/E') ratio: 25.5 +/- 1.9 vs. 14.9 +/- 0.9]. INaL in LV myocytes from HS rats was significantly increased to 0.41 +/- 0.02 from 0.14 +/- 0.02 pA/pF in NS rats. The action potential duration (APD) was prolonged to 136 +/- 12 from 68 +/- 9 ms in NS rats. QTc intervals were longer in HS vs. NS rats (267 +/- 8 vs. 212 +/- 2 ms). Acute and chronic treatment with GS-967 decreased the enhanced INaL to 0.24 +/- 0.01 and 0.17 +/- 0.02 pA/pF, respectively, vs. 0.41 +/- 0.02 pA/pF in the HS group. Chronic treatment with GS-967 dose-dependently reduced LV mass, the increases in E/E' ratio, and the prolongation of IVRT by 27, 27, and 20%, respectively, at the 1.0 mg.kg(-1).day(-1) dose without affecting blood pressure or LV systolic function. The prolonged APDs in myocytes and QTc of HS rats were significantly reduced with GS-967 treatment. These results indicate that INaL is a significant contributor to the LV diastolic dysfunction, hypertrophy, and repolarization abnormalities and thus, inhibition of this current is a promising therapeutic target for diastolic heart failure. PMID- 26993229 TI - Sex differences in the impact of CYP2C19 polymorphisms and low-grade inflammation on coronary microvascular disorder. AB - Categorization as a cytochrome P-450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. It is correlated with an increase in the circulating levels of high-sense C-reactive protein (hs CRP) in women only, although its role in coronary microcirculation is unclear. We examined sex differences in the impact of the CYP2C19 genotype and low-grade inflammation on coronary microvascular disorder (CMVD). We examined CYP2C19 genotypes in patients with CMVD (n = 81) and in healthy subjects as control (n = 81). CMVD was defined as the absence of coronary artery stenosis and epicardial spasms, the presence of inverted lactic acid levels between the intracoronary and coronary sinuses, or an adenosine triphosphate-induced coronary flow reserve ratio < 2.5. CYP2C19 PMs have two loss-of-function (LOF) alleles (*2, *3). Extensive metabolizers have no LOF alleles, and intermediate metabolizers have one LOF allele. The ratio of CYP2C19 PM and hs-CRP levels in CMVD was significantly higher than that of controls, especially in women (40.9 vs. 13.8%, P = 0.013; 0.11 +/- 0.06 vs. 0.07 +/- 0.04 mg/dl, P = 0.001). Moreover, in each CYP2C19 genotype, hs-CRP levels in CMVD in CYP2C19 PMs were significantly higher than those of the controls, especially in women (0.15 +/- 0.06 vs. 0.07 +/- 0.03, P = 0.004). Multivariate analysis for CMVD indicated that the female sex, current smoking, and hypertension were predictive factors, and that high levels of hs-CRP and CYP2C19 PM were predictive factors in women only (odds ratio 3.5, 95% confidence interval 1.26-9.93, P = 0.033; odds ratio 4.1, 95% confidence interval 1.15-14.1, P = 0.038). CYP2C19 PM genotype may be a new candidate risk factor for CMVD via inflammation exclusively in the female population. PMID- 26993230 TI - Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig. AB - Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15-20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 +/- 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID- 26993231 TI - Molecular and cellular characterization of GA-Stimulated Transcripts GASA4 and GASA6 in Arabidopsis thaliana. AB - GA and ABA play antagonistic roles in numerous cellular processes essential for growth, development, and stress responses. GASA4 and GASA6 belong to a family of GA-Stimulated transcripts in Arabidopsis, known as GA-inducible and ABA repressible. We have found that GASA4 and GASA6 expression is likely mediated through a repressor of GA responses, GA INSENSITIVE (GAI) protein. Moreover, GASA4 and GASA6 are in general up regulated by growth hormones (auxin, BR, cytokinin, and GA) and down regulated by stress hormones (ABA, JA, and SA), indicating a role of GASA4 and GASA6 in hormone crosstalk. Genetic analyses show that suppression of both GASA4 and GASA6 causes late flowering, while over expression of GASA6 causes early flowering in Arabidopsis. GASA family members encode small polypeptides sharing common structural features: an N-terminal signal peptide, a highly divergent intermediate region, and a conserved C terminal domain containing 12 conserved cysteines. Despite the presence of a signal peptide, it has not been determined whether or not GASA4 and GASA6 can be processed in vivo. By using imaging and immunological analyses, we show that the N-terminal signal peptide is cleaved as predicted, and the cleavage is important for proper sub-cellular localization of GASA4 and GASA6. PMID- 26993232 TI - 1-MCP treatment enhanced expression of genes controlling endosperm cell division and starch biosynthesis for improvement of grain filling in a dense-panicle rice cultivar. AB - High ethylene production in dense-panicle rice cultivars impacts grain filling. 1 MCP (ethylene action inhibitor) treatment increased assimilates partitioning, cell number and size and expression of starch synthesizing enzyme genes of developing caryopses mostly in the basal spikelets of panicle at early post anthesis stage. The gain in cell number was less compared to the increase of size. High ethylene production in spikelets matched with greater expression of ethylene receptor and signal transducer genes. Genes encoding cell cycle regulators CDK, CYC and CKI expressed poorly on 9 DAA. 1-MCP treatment enhanced their expression; the increase of expression was higher for CDKs and lower for CKIs in basal compared to apical spikelets. Greater expression of CDKB2:1 might have lifted cytokinesis of nascent peripheral cells of endosperm, while promotion of CDKAs, CYCD2:2 and inhibition of CYCB2:2 expression contributed to endoreduplication of central cells increasing cell size and DNA ploidy level. It is concluded that the process of endoreduplication, which begins at mid-grain filling stage, is crucially linked with the final caryopsis size of rice grain. The enhanced endosperm growth brought about by repressed ethylene action during the first few days after anthesis seems to be associated with the overall increased cell cycle activity and sink strength. PMID- 26993233 TI - Expression and interaction of the mango ethylene receptor MiETR1 and different receptor versions of MiERS1. AB - Different versions of the mango ethylene receptor MiERS1 were identified and the analysis indicates that, in addition to MiERS1, two short versions of this receptor (MiERS1m, MiERS1s), representing truncated proteins with central deletions of functional domains, are present in mango. The short receptor versions reveal a different expression pattern compared to MiERS1, and they are highly variably transcribed. With transient expression assays using fluorescent fusion proteins, the localisation and the interaction of the receptors were determined in leaf cells of the tobacco model. MiERS1, MiETR1, and the short MiERS1 receptor versions are anchored in the endoplasmic reticulum (ER) membrane and co-localise with each other and with an ER-marker. Furthermore, ectopic expression of the mango receptors appears to induce a re-organisation of the ER resulting in accumulation of ER bodies. Interaction assays suggest that both short MiERS1 receptor versions can bind to proteins located in the ER. Bi molecular fluorescence complementation (BiFC) assays indicate, that MiERS1m may dimerise with itself and can also interact with MiERS1, but not with MiETR1. Further, it as found that MiETR1 can interact with MiERS1. Interaction of MiERS1s with the other ethylene receptors could not be detected, although it was located in the ER membrane system. PMID- 26993234 TI - A two-dimensional microscale model of gas exchange during photosynthesis in maize (Zea mays L.) leaves. AB - CO2 exchange in leaves of maize (Zea mays L.) was examined using a microscale model of combined gas diffusion and C4 photosynthesis kinetics at the leaf tissue level. Based on a generalized scheme of photosynthesis in NADP-malic enzyme type C4 plants, the model accounted for CO2 diffusion in a leaf tissue, CO2 hydration and assimilation in mesophyll cells, CO2 release from decarboxylation of C4 acids, CO2 fixation in bundle sheath cells and CO2 retro-diffusion from bundle sheath cells. The transport equations were solved over a realistic 2-D geometry of the Kranz anatomy obtained from light microscopy images. The predicted responses of photosynthesis rate to changes in ambient CO2 and irradiance compared well with those obtained from gas exchange measurements. A sensitivity analysis showed that the CO2 permeability of the mesophyll-bundle sheath and airspace-mesophyll interfaces strongly affected the rate of photosynthesis and bundle sheath conductance. Carbonic anhydrase influenced the rate of photosynthesis, especially at low intercellular CO2 levels. In addition, the suberin layer at the exposed surface of the bundle sheath cells was found beneficial in reducing the retro-diffusion. The model may serve as a tool to investigate CO2 diffusion further in relation to the Kranz anatomy in C4 plants. PMID- 26993235 TI - Targeted expression of cystatin restores fertility in cysteine protease induced male sterile tobacco plants. AB - Fertility restoration in male sterile plants is an essential requirement for their utilization in hybrid seed production. In an earlier investigation, we have demonstrated that the targeted expression of a cysteine protease in tapetal cell layer resulted in complete male sterility in tobacco transgenic plants. In the present investigation, we have used a cystatin gene, which encodes for a cysteine protease inhibitor, from a wild peanut, Arachis diogoi and developed a plant gene based restoration system for cysteine protease induced male sterile transgenic tobacco plants. We confirmed the interaction between the cysteine protease and a cystatin of the wild peanut, A. diogoi through in silico modeling and yeast two hybrid assay. Pollen from primary transgenic tobacco plants expressing cystatin gene under the tapetum specific promoter- TA29 restored fertility on cysteine protease induced male sterile tobacco plants developed earlier. This has confirmed the in vivo interaction of cysteine protease and cystatin in the tapetal cells, and the inactivation of cysteine protease and modulation of its negative effects on pollen fertility. Both the cysteine protease and cystatin genes are of plant origin in contrast to the analogous barnase-barstar system that deploys genes of prokaryotic origin. Because of the deployment of genes of plant origin, this system might not face biosafety problems in developing hybrids in food crops. PMID- 26993236 TI - Unusual RNA plant virus integration in the soybean genome leads to the production of small RNAs. AB - Horizontal gene transfer (HGT) is known to be a major force in genome evolution. The acquisition of genes from viruses by eukaryotic genomes is a well-studied example of HGT, including rare cases of non-retroviral RNA virus integration. The present study describes the integration of cucumber mosaic virus RNA-1 into soybean genome. After an initial metatranscriptomic analysis of small RNAs derived from soybean, the de novo assembly resulted a 3029-nt contig homologous to RNA-1. The integration of this sequence in the soybean genome was confirmed by DNA deep sequencing. The locus where the integration occurred harbors the full RNA-1 sequence followed by the partial sequence of an endogenous mRNA and another sequence of RNA-1 as an inverted repeat and allowing the formation of a hairpin structure. This region recombined into a retrotransposon located inside an exon of a soybean gene. The nucleotide similarity of the integrated sequence compared to other Cucumber mosaic virus sequences indicates that the integration event occurred recently. We described a rare event of non-retroviral RNA virus integration in soybean that leads to the production of a double-stranded RNA in a similar fashion to virus resistance RNAi plants. PMID- 26993237 TI - CIPK23 is involved in iron acquisition of Arabidopsis by affecting ferric chelate reductase activity. AB - Iron deficiency is one of the major limiting factors affecting quality and production of crops in calcareous soils. Numerous signaling molecules and transcription factors have been demonstrated to play a regulatory role in adaptation of plants to iron deficiency. However, the mechanisms underlying the iron deficiency-induced physiological processes remain to be fully dissected. Here, we demonstrated that the protein kinase CIPK23 was involved in iron acquisition. Lesion of CIPK23 rendered Arabidopsis mutants hypersensitive to iron deficiency, as evidenced by stronger chlorosis in young leaves and lower iron concentration than wild-type plants under iron-deficient conditions by down regulating ferric chelate reductase activity. We found that iron deficiency evoked an increase in cytosolic Ca(2+) concentration and the elevated Ca(2+) would bind to CBL1/CBL9, leading to activation of CIPK23. These novel findings highlight the involvement of calcium-dependent CBL-CIPK23 complexes in the regulation of iron acquisition. Moreover, mutation of CIPK23 led to changes in contents of mineral elements, suggesting that CBL-CIPK23 complexes could be as "nutritional sensors" to sense and regulate the mineral homeostasis in Arabisopsis. PMID- 26993238 TI - Functionality of soybean CBF/DREB1 transcription factors. AB - Soybean (Glycine max) is considered to be cold intolerant and is not able to significantly acclimate to cold/freezing stress. In most cold tolerant plants, the C-repeat/DRE Binding Factors (CBF/DREBs) are critical contributors to successful cold-responses; rapidly increasing following cold treatment and regulating the induction of many cold responsive genes. In soybean vegetative tissue, we found strong, transient accumulation of CBF transcripts in response to cold stress; however, the soybean transcripts of typical cold responsive genes (homologues to Arabidopsis genes such as dehydrins, ADH1, RAP2.1, and LEA14) were not significantly altered. Soybean CBFs were found to be functional, as when expressed constitutively in Arabidopsis they increased the levels of AtCOR47 and AtRD29a transcripts and increased freezing tolerance as measured by a decrease in leaf freezing damage and ion leakage. Furthermore the constitutive expression of GmDREB1A;2 and GmDREB1B;1 in Arabidopsis led to stronger up-regulation of downstream genes and more freezing tolerance than GmDREB1A;1, the gene whose transcript is the major contributor to total CBF/DREB1 transcripts in soybean. The inability for the soybean CBFs to significantly up regulate the soybean genes that contribute to cold tolerance is consistent with poor acclimation capability and the cold intolerance of soybean. PMID- 26993239 TI - Dissection of Arabidopsis NCED9 promoter regulatory regions reveals a role for ABA synthesized in embryos in the regulation of GA-dependent seed germination. AB - Nine-cis-epoxycarotenoid dioxygenase (NCED) catalyzes the key step of abscisic acid (ABA) biosynthesis. There are five genes encoding NCED in Arabidopsis, which differentially regulate ABA biosynthesis in a spatiotemporal manner in response to endogenous and environmental stimuli. Previous studies have shown that NCED9 is expressed in testa and embryos during seed development. In the present study, we have identified promoter regions required for the expression of NCED9 in testa and embryos, respectively. Electrophoretic mobility shift assays (EMSA) and yeast one-hybrid (Y1H) assays showed that several homeodomain-leucine zipper (HD-Zip) proteins, namely ATHBs, bound to the sequence required for expression of NCED9 in testa, suggesting that they redundantly regulate NCED9 expression. By expressing the NCED9 gene under the control of a deleted NCED9 promoter in an nced9 mutant expression was limited to embryos. Transformants were complemented for the paclobutrazol resistant germination phenotype of the mutant, suggesting that the ABA synthesis mediated by NCED9 in embryos plays an important role in the regulation of gibberellin (GA)-dependent seed germination. PMID- 26993240 TI - Expression and characterization of a barley phosphatidylinositol transfer protein structurally homologous to the yeast Sec14p protein. AB - Phosphatidylinositol transfer proteins (PITPs) include a large group of proteins implicated in the non-vesicular traffic of phosphatidylinositol (PI) between membranes. In yeast, the structure and function of the PITP Sec14-p protein have been well characterized. In contrast, the knowledge on plant PITP proteins is very scarce. In this work, we characterized a novel type of PITP protein in barley named HvSec14p and related to the yeast Sec14-p protein. Our data reveal that HvSec14p consists of only the Sec14p-domain structurally homologous to the yeast phosphoinositide binding domain. We show that HvSec14p expression is up regulated at both transcript and protein levels at specific stages of development during seed formation and germination, and in leaves of a drought-tolerant barley genotype under osmotic constraints. Modeling analyses of the protein three dimensional structure revealed its capacity to dock the phosphoinositides, PtdIns(3)P, PtdIns(4)P, PtdIns(5)P and PtdIns(3,5)P2. Consistently, the recombinant HvSec14p protein is able to bind in vitro most PIP types, the highest affinity being observed with PtdIns(3,5)P2. Based on the high gene expression at specific developmental stages and in drought-tolerant barley genotypes, we propose that HvSec14p plays essential roles in the biogenesis of membranes in expanding cells and in their preservation under osmotic stress conditions. PMID- 26993241 TI - Galactinol as marker for seed longevity. AB - Reduced seed longevity or storability is a major problem in seed storage and contributes to increased costs in crop production. Here we investigated whether seed galactinol contents could be predictive for seed storability behavior in Arabidopsis, cabbage and tomato. The analyses revealed a positive correlation between galactinol content and seed longevity in the three species tested, which indicates that this correlation is conserved in the Brassicaceae and beyond. Quantitative trait loci (QTL) mapping in tomato revealed a co-locating QTL for galactinol content and seed longevity on chromosome 2. A candidate for this QTL is the GALACTINOL SYNTHASE gene (Solyc02g084980.2.1) that is located in the QTL interval. GALACTINOL SYNTHASE is a key enzyme of the raffinose family oligosaccharide (RFO) pathway. To investigate the role of enzymes in the RFO pathway in more detail, we applied a reverse genetics approach using T-DNA knock out lines in genes encoding enzymes of this pathway (GALACTINOL SYNTHASE 1, GALACTINOL SYNTHASE 2, RAFFINOSE SYNTHASE, STACHYOSE SYNTHASE and ALPHA GALACTOSIDASE) and overexpressors of the cucumber GALACTINOL SYNTHASE 2 gene in Arabidopsis. The galactinol synthase 2 mutant and the galactinol synthase 1 galactinol synthase 2 double mutant contained the lowest seed galactinol content which coincided with lower seed longevity. These results show that galactinol content of mature dry seed can be used as a biomarker for seed longevity in Brassicaceae and tomato. PMID- 26993242 TI - Review: The future of cystatin engineering. AB - Plant cystatins are naturally occurring protease inhibitors that prevent proteolysis by papain-like cysteine proteases. Their protective action against environmental stresses has been relatively well characterised. Still, there is a need to greatly improve both potency and specificity based on the current rather poor performance of cystatins in biotechnological applications. Research in creating more potent and specific cystatins, including amino acid substitutions in either conserved cystatin motifs and/or at variable amino acid sites, is reviewed. Existing gaps for better understanding of cystatin-protease interactions are further explored. Current knowledge on multi-cystatins or hybrid protease inhibitors involving cystatins as an additional option for cystatin engineering is further outlined along with the nuances of how cystatins with rather unusual amino acid sequences might actually help in cystatin engineering. Finally, future opportunities for application of cystatins are highlighted which include applications in genetically modified transgenic plants for environmental stress protection and also as nutraceuticals, as part of more nutritious food. Further opportunities might also include the possible management of diseases and disorders, often associated with lifestyle changes, and the most immediate and promising application which is inclusion into plant-based recombinant protein production platforms. PMID- 26993243 TI - Dissection of Trichoderma longibrachiatum-induced defense in onion (Allium cepa L.) against Fusarium oxysporum f. sp. cepa by target metabolite profiling. AB - Trichoderma spp. are versatile opportunistic plant symbionts that can cause substantial changes in the metabolism of host plants, thereby increasing plant growth and activating plant defense to various diseases. Target metabolite profiling approach was selected to demonstrate that Trichoderma longibrachiatum isolated from desert soil can confer beneficial agronomic traits to onion and induce defense mechanism against Fusarium oxysporum f. sp. cepa (FOC), through triggering a number of primary and secondary metabolite pathways. Onion seeds primed with Trichoderma T1 strain displayed early seedling emergence and enhanced growth compared with Trichoderma T2-treatment and untreated control. Therefore, T1 was selected for further investigations under greenhouse conditions, which revealed remarkable improvement in the onion bulb growth parameters and resistance against FOC. The metabolite platform of T1-primed onion (T1) and T1 primed onion challenged with FOC (T1+FOC) displayed significant accumulation of 25 abiotic and biotic stress-responsive metabolites, representing carbohydrate, phenylpropanoid and sulfur assimilation metabolic pathways. In addition, T1- and T1+FOC-treated onion plants showed discrete antioxidant capacity against 1,1 diphenyl-2-picrylhydrazyl (DPPH) compared with control. Our findings demonstrated the contribution of T. longibrachiatum to the accumulation of key metabolites, which subsequently leads to the improvement of onion growth, as well as its resistance to oxidative stress and FOC. PMID- 26993245 TI - [Differences between MDRD-4 and CG in the prevalence of renal failure and its associated variables in type2 diabetic patients]. AB - OBJECTIVE: To estimate the prevalence of occult renal failure (RF) in DM2, by comparing two formulas for estimating glomerular filtration rate (GFR): Modification of Diet in Renal Disease 4 (MDRD-4) and Cockcroft-Gault (CG), as well as their associated clinical variables. DESIGN: Multicentre analytical cross sectional. LOCATION: Two basic Primary Care areas in Terres de l'Ebre, in North Eastern Spain. PARTICIPANTS: A total of 493 DM2 patients with age >18years with an assigned doctor in the areas studied. There was a loss of 9 and 11 cases in each formula due to lack of variables necessary for the GFR. MAIN MEASUREMENTS: Estimated GFR using the two formulas, plasma creatinine values, classification of patients with established RF, occult RF and without RF, and possible clinical pathological variables associated with RF. RESULTS: Of the total, 45.2% were men, the mean age was 70.4 years, and mean time since onset of diabetes of 7.5 years. The prevalence of occult RF with MDRD-4 was 18%, and 22.6% with CG. The cases detected by GC and not by MDRD-4 were higher, and with lower weight. In both formulas, occult RF patients had more chronic diseases, hypertension, and cardiovascular events (CV) than those without RF. Risk factors associated with occult RF were female, increasing age, and LDL cholesterol. CONCLUSIONS: The prevalence of occult RF was 20% in DM2, independently of the formula. A poorer control of cardiovascular risk factors was observed, which makes them a group at higher risk of suffering a CV event. PMID- 26993244 TI - Characterization of senescence-associated protease activities involved in the efficient protein remobilization during leaf senescence of winter oilseed rape. AB - Oilseed rape (Brassica napus L.) is a crop plant characterized by a poor nitrogen (N) use efficiency that is mainly due to low N remobilization efficiency during the sequential leaf senescence of the vegetative stage. As a high leaf N remobilization efficiency was strongly linked to a high remobilization of proteins during leaf senescence of rapeseed, our objective was to identify senescence-associated protease activities implicated in the protein degradation. To reach this goal, leaf senescence processes and protease activities were investigated in a mature leaf becoming senescent in plants subjected to ample or low nitrate supply. The characterization of protease activities was performed by using in vitro analysis of RuBisCO degradation with or without inhibitors of specific protease classes followed by a protease activity profiling using activity-dependent probes. As expected, the mature leaf became senescent regardless of the nitrate treatment, and nitrate limitation enhanced the senescence processes associated with an enhanced degradation of soluble proteins. The characterization of protease activities revealed that: (i) aspartic proteases and the proteasome were active during senescence regardless of nitrate supply, and (ii) the activities of serine proteases and particularly cysteine proteases (Papain-like Cys proteases and vacuolar processing enzymes) increased when protein remobilization associated with senescence was accelerated by nitrate limitation. Short statement: Serine and particularly cysteine proteases (both PLCPs and VPEs) seem to play a crucial role in the efficient protein remobilization when leaf senescence of oilseed rape was accelerated by nitrate limitation. PMID- 26993246 TI - Ivory phalanx: A specific and not widely known finding in psoriatic arthritis. PMID- 26993247 TI - Parapharyngeal metastasis of an occult thyroid carcinoma. PMID- 26993248 TI - Biliary fistula between the gallbladder and post-radiofrequency hepatic necrosis. PMID- 26993249 TI - Promotion of tumour proliferation, migration and invasion by miR-92b in targeting RECK in osteosarcoma. AB - MicroRNAs play important roles in the development of cancers. Although miR-92b has been reported to promote the tumorigenesis of some cancers, its role in osteosarcoma remains unknown. In the present study, we focused on the expression, function and mechanisms of miR-92b in osteosarcoma development. The miRNA miR-92b was up-regulated in osteosarcoma cell lines and tissues; miR-92b up-regulation correlated with poor prognosis in osteosarcoma. Overexpression of miR-92b promoted osteosarcoma cell proliferation, migration and invasion, which was abrogated by miR-92b inhibition. Reversion-inducing, cysteine-rich protein with kazal motifs (RECK) was identified as the direct and functional target of miR-92b in osteosarcoma. Importantly, restoring RECK expression abrogated increases in cell growth, motility and invasiveness induced by miR-92b RECK was down-regulated in osteosarcoma tissues, and its expression level negatively correlated with miR 92b Collectively, our results indicate that miR-92b acts as an oncogenic miRNA and may be a therapeutic target in osteosarcoma. PMID- 26993250 TI - Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: role of miR-143. AB - A predisposing factor for development of the hyperglycaemic state of gestational diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal obesity is associated with significant reductions in placental mitochondrial respiration. MicroRNA (miR)-143 has been previously shown to regulate the metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer tissues. We hypothesized that mitochondrial respiration is reduced and aerobic glycolysis is up-regulated via changes in miR-143 expression in the placenta of women with GDM. Placental tissue was collected at term from women with A1GDM (controlled by diet), A2GDM (controlled by medication) and body mass index (BMI) matched controls (CTRL). miR-143 expression was measured by RT-PCR. Expression of mitochondrial complexes, transcription factors peroxisome proliferator-activated receptor-gamma co-activator 1alpha (PGC1alpha) and peroxisome proliferator activated receptor gamma (PPARgamma), components of mammalian target of rapamycin (mTOR) signalling, glucose transporter GLUT1 and glycolytic enzymes [hexokinase-2 (HK-2), phosphofructokinase (PFK) and lactate dehydrogenase (LDH)] were measured by Western blot. Trophoblast respiration was measured by XF24 Analyser. Expression of miR-143, mitochondrial complexes, and PPARgamma and PGC1alpha, which act downstream of miR-143, were significantly decreased in A2GDM placentae compared with A1GDM and CTRL (P<0.01). Placental hPL (human placental lactogen) levels, expression of glycolytic enzymes, GLUT1 and mTOR signalling were also significantly increased by more than 2-fold in A2GDM compared with A1GDM and CTRL (P<0.05). There was a 50% reduction in mitochondrial respiration in trophoblast cells isolated from A2GDM placentae. Overexpression of miR-143 was able to increase mitochondrial respiration, increase protein expression of mitochondrial complexes and decrease expression of glycolytic enzymes by 40% compared with A2GDM. Down-regulation of miR-143 mediates the metabolic switch from oxidative phosphorylation to aerobic glycolysis in placenta of women with A2GDM. PMID- 26993251 TI - Paraoxonase-1 overexpression prevents experimental abdominal aortic aneurysm progression. AB - Abdominal aortic aneurysm (AAA) is a permanent dilation of the aorta due to excessive proteolytic, oxidative and inflammatory injury of the aortic wall. We aimed to identify novel mediators involved in AAA pathophysiology, which could lead to novel therapeutic approaches. For that purpose, plasma from four AAA patients and four controls were analysed by a label-free proteomic approach. Among identified proteins, paraoxonase-1 (PON1) was decreased in plasma of AAA patients compared with controls, which was further validated in a bigger cohort of samples by ELISA. The phenylesterase enzymatic activity of PON1 was also decreased in serum of AAA patients compared with controls. To address the potential role of PON1 as a mediator of AAA, experimental AAA was induced by aortic elastase perfusion in wild-type (WT) mice and human transgenic PON1 (HuTgPON1) mice. Similar to humans, PON1 activity was also decreased in serum of elastase-induced AAA mice compared with healthy mice. Interestingly, overexpression of PON1 was accompanied by smaller aortic dilation and higher elastin and vascular smooth muscle cell (VSMC) content in the AAA of HuTgPON1 compared with WT mice. Moreover, HuTgPON1 mice display decreased oxidative stress and apoptosis, as well as macrophage infiltration and monocyte chemoattractant protein-1 (MCP1) expression, in elastase-induced AAA. In conclusion, decreased circulating PON1 activity is associated with human and experimental AAA. PON1 overexpression in mice protects against AAA progression by reducing oxidative stress, apoptosis and inflammation, suggesting that strategies aimed at increasing PON1 activity could prevent AAA. PMID- 26993252 TI - Psychosocial Impact of the Bionic Pancreas During Summer Camp. AB - BACKGROUND: The psychosocial impact of the bionic pancreas (BP) was assessed among children attending diabetes camp. METHODS: Nineteen children were randomly assigned for 5 days to the BP condition and 5 days to the control condition in a crossover design. RESULTS: Significant reductions in hypoglycemic fear and regimen burden were found. Children felt less burdened or worried about diabetes and felt freer to do things they enjoyed while using the BP. Children wished the BP responded to out of range numbers faster and expressed annoyance about carrying around the necessary equipment. CONCLUSIONS: Children may experience improved psychosocial outcomes following use of BP while expressing key areas of user concern. Future studies in less controlled environments with larger sample sizes can determine if these findings are generalizable to other groups. PMID- 26993253 TI - Preliminary Evaluation of a Long-Term Intraperitoneal Glucose Sensor With Flushing Mechanism. PMID- 26993254 TI - Routine HIV and sexually transmitted infection testing in an abortion service: 6 years' experience. PMID- 26993255 TI - Two variants of the major serine protease inhibitor from the sea anemone Stichodactyla helianthus, expressed in Pichia pastoris. AB - The major protease inhibitor from the sea anemone Stichodactyla helianthus (ShPI 1) is a non-specific inhibitor that binds trypsin and other trypsin-like enzymes, as well as chymotrypsin, and human neutrophil elastase. We performed site directed mutagenesis of ShPI-1 to produce two variants (rShPI-1/K13L and rShPI/Y15S) that were expressed in Pichia pastoris, purified, and characterized. After a single purification step, 65 mg and 15 mg of protein per liter of culture supernatant were obtained for rShPI-1/K13L and rShPI/Y15S, respectively. Functional studies demonstrated a 100-fold decreased trypsin inhibitory activity as result of the K13L substitution at the reactive (P1) site. This protein variant has a novel tight-binding inhibitor activity of pancreatic elastase and increased activity toward neutrophil elastase in comparison to rShPI-1A. In contrast, the substitution Y15S at P2' site did not affect the Ki value against trypsin, but did reduce activity 10-fold against chymotrypsin and neutrophil elastase. Our results provide two new ShPI-1 variants with modified inhibitory activities, one of them with increased biomedical potential. This study also offers new insight into the functional impact of the P1 and P2' sites on ShPI-1 specificity. PMID- 26993257 TI - Imaging of occult hip fractures: CT or MRI? AB - OBJECTIVES: Patients presenting with hip pain but normal plain radiographs may ultimately be shown on further investigation to have suffered an occult hip fracture (OHF). This diagnosis can be made with CT or MRI. Traditionally MRI has been considered a superior modality. We performed a retrospective review of all patients presenting to our service with a suspected OHF over a four-year period, investigated with either CT or MRI. DESIGN: Retrospective review. SETTING: Urban trauma centre. PATIENTS: Patients with suspected hip fractures and negative radiographs. INTERVENTION: CT or MRI. MAIN OUTCOME MEASURES: Detection rate; delay in request for further imaging; delay to theatre; re-presentations with missed fractures. RESULTS: A total of 179 patients were investigated, with a mean age of 82+/-13 years. The ultimate diagnosis was of an OHF in 71 cases and pelvic or acetabular fracture in 34. The average time from presentation plain radiograph to further imaging was 2.0+/-2.7 days, but was significantly shorter for CT. No patient re-presented with unidentified fractures or other localised hip pathology within a 12-month period. CONCLUSIONS: Modern imaging technology does not appear to miss clinically significant fractures. As CT is usually more accessible than MRI, the results of our study should encourage surgeons to consider CT as a first line investigation for occult hip fractures. We advocate a high index of suspicion and early imaging referral for elderly patients presenting with non specific hip pain following a fall. Level 3 Evidence. PMID- 26993258 TI - Letter to the Editor. PMID- 26993256 TI - The Complex Admixture History and Recent Southern Origins of Siberian Populations. AB - Although Siberia was inhabited by modern humans at an early stage, there is still debate over whether it remained habitable during the extreme cold of the Last Glacial Maximum or whether it was subsequently repopulated by peoples with recent shared ancestry. Previous studies of the genetic history of Siberian populations were hampered by the extensive admixture that appears to have taken place among these populations, because commonly used methods assume a tree-like population history and at most single admixture events. Here we analyze geogenetic maps and use other approaches to distinguish the effects of shared ancestry from prehistoric migrations and contact, and develop a new method based on the covariance of ancestry components, to investigate the potentially complex admixture history. We furthermore adapt a previously devised method of admixture dating for use with multiple events of gene flow, and apply these methods to whole-genome genotype data from over 500 individuals belonging to 20 different Siberian ethnolinguistic groups. The results of these analyses indicate that there have been multiple layers of admixture detectable in most of the Siberian populations, with considerable differences in the admixture histories of individual populations. Furthermore, most of the populations of Siberia included here, even those settled far to the north, appear to have a southern origin, with the northward expansions of different populations possibly being driven partly by the advent of pastoralism, especially reindeer domestication. These newly developed methods to analyze multiple admixture events should aid in the investigation of similarly complex population histories elsewhere. PMID- 26993259 TI - Apontic regulates somatic stem cell numbers in Drosophila testes. AB - BACKGROUND: Microenvironments called niches maintain resident stem cell populations by balancing self-renewal with differentiation, but the genetic regulation of this process is unclear. The niche of the Drosophila testis is well characterized and genetically tractable, making it ideal for investigating the molecular regulation of stem cell biology. The JAK/STAT pathway, activated by signals from a niche component called the hub, maintains both germline and somatic stem cells. RESULTS: This study investigated the molecular regulation of the JAK/STAT pathway in the stem cells of the Drosophila testis. We determined that the transcriptional regulator Apontic (Apt) acts in the somatic (cyst) stem cells (CySCs) to balance differentiation and maintenance. We found Apt functions as a negative feedback inhibitor of STAT activity, which enables cyst cell maturation. Simultaneous loss of the STAT regulators apt and Socs36E, or the Stat92E-targeting microRNA miR-279, expanded the somatic stem cell-like population. CONCLUSIONS: Genetic analysis revealed that a conserved genetic regulatory network limits JAK/STAT activity in the somatic stem cells of Drosophila testis. In these cells, we determined JAK/STAT signaling promotes apt expression. Then, Apt functions through Socs36E and miR-279 to attenuate pathway activation, which is required for timely CySC differentiation. We propose that Apt acts as a core component of a STAT-regulatory circuit to prevent stem cell overpopulation and allow stem cell maturation. PMID- 26993260 TI - Exploratory serum fatty acid patterns associated with blood pressure in community dwelling middle-aged and elderly Chinese. AB - BACKGROUND: Epidemiological studies have assessed relationships between circulating levels of fatty acid (FA) and blood pressure (BP), and their results remain controversial. Nevertheless, data are sparse on serum FA as biomarker and BP in China. The aim of the study was to investigate the association between serum FA and BP in Chinese populations. METHODS: We conducted a cross-sectional study nested within a community-based cohort of 2447 Chinese participants aged 35 79 years who completed a baseline assessment between October 2012 and April 2013. Baseline assessment included the collection of fasting blood samples, anthropometric measurements and a personal interview using a validated questionnaire. Serum FA was determined by gas-liquid chromatography. Exploratory factor analyses were employed to identify FA-factor as a reflection of serum FA pattern. A multiple regression model was conducted to estimate adjusted mean of BP with 95% confidence interval (CI) by tertile groups of the generated FA-factor scores. RESULTS: Hypertensive patients have significantly higher serum 14:0, 16:0, 16:1n-7, 18:3n-6, 20:3n-6 and Delta(6)-desaturase index (18:3n-6/18:2n-6) as well as lower 18:2n-6, 22:6n-3 and Delta(5)-desaturase index (20:4n-6/20:3n-6) compared with normotensive participants. Factor 1 (low linoleic acid/high saturated FA pattern: 14:0, 16:0, 16:1n-7, 18:2n-6, 18:3n-6, 20:3n-6) and Factor 2 (n-3 PUFA pattern: 20:5n-3, 22:5n-3, 22:6n-3, 18:1n-9) were identified as indicators of the serum FA pattern. After adjustment for age, gender, body mass index, hypertension treatment, smoking, alcohol intake, education, profession, exercise habit, salt intake, family history of hypertension, heart rate, blood lipids and fasting blood-glucose levels, per a standard deviation (SD) increment of Factor 1 scores was associated with an increment of 2.44 (95% CI: 1.73, 3.15) mm Hg for systolic BP, whereas per a SD increment of Factor 2 scores was associated with a reduction of 1.40 (95% CI: 0.80, 2.04) mm Hg for diastolic BP. CONCLUSIONS: The serum FA pattern characterized by low proportions of 14:0, 16:0, 16:1n-7 and 18:3n-6 as well as high 18:2n-6 and 22:6n-3 was beneficially associated with BP levels in this Chinese population. This evidence well supports the current dietary recommendations in the communities to replace saturated fat with polyunsaturated fat. PMID- 26993262 TI - Modified low-density lipoprotein may moderate the association of baseline hs-CRP with incident cardiac events in the Asian populations. PMID- 26993263 TI - Predictors of reversible severe functional tricuspid regurgitation in patients with atrial fibrillation. AB - BACKGROUND: Atrial remodeling associated with atrial fibrillation (AF) is known to be a risk factor for significant tricuspid regurgitation (TR), but the predictor of reversible TR in patients with severe functional TR and AF has been poorly studied. The aim of this study was to investigate the predictors of reversible TR in patients with severe functional TR and AF. METHODS: Among 232 patients with severe TR, a total of 71 patients with severe functional TR and AF were enrolled and divided into 2 groups: reversible TR group (n=16, 70.1+/-15.5 years, 7 males) vs. non-reversible TR group (n=55, 72.3+/-11.8 years, 20 males). Improvement of TR to moderate or lesser degree on follow-up (FU) echocardiography was considered as reversible TR in the present study. RESULTS: During 38.9+/-26.7 months of FU period, reversible TR was observed in 16 patients (22.5%). The presence of left ventricular (LV) systolic dysfunction was significantly prevalent (43.8% vs. 20.0%, p=0.03) and the improvement in LV ejection fraction (EF) more than 10% on FU echocardiography was more significantly frequent (62.5% vs. 23.3%, p=0.003) in the reversible TR group than in the non-reversible TR group. However, the other echocardiographic parameters, including right ventricular function were not different between the groups. In multivariate analysis using Cox proportional hazard model, the improvement of LVEF more than 10% was the only independent predictor of reversible TR (HR=7.39, 95%CI 1.80 30.28, p=0.005). Nine patients died only in patients with non-reversible TR (12.7%), but the reversibility of TR was not associated with mortality. CONCLUSIONS: The improvement of LV systolic function was the only independent predictor of reversible TR. Appropriate medical therapy including management for heart failure should be considered before performing surgery in patients with severe functional TR and AF, especially in patients with LV dysfunction. PMID- 26993261 TI - Early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury (The ELAIN-Trial): study protocol for a randomized controlled trial. AB - BACKGROUND: Acute kidney injury remains a common complication in critically ill patients and despite multiple trials and observational studies, the optimal timing for initiation of renal replacement therapy is still unclear. The early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury (ELAIN) study is a randomized, single-center, prospective, two-arm, parallel group trial to reduce mortality in patients with severe acute kidney injury. We describe the study design and discuss aspects of the need for a trial in this patient cohort. METHODS/DESIGN: Our plan is to randomize critically ill patients with acute kidney injury to 'early' or 'late' initiation of renal replacement therapy according to stage 2 and 3 of the KDIGO classification using a specific trial protocol. We plan to guide data collection and analysis using pre-existing definitions and testing. The primary endpoint is overall survival in a 90-day follow-up period. Secondary endpoints include 28 day, 60-day, 90-day and 1-year all-cause mortality, recovery of renal function, ICU and hospital length-of-stay. The primary analysis will be an intention-to treat analysis; secondary analyses include treated analyses. We will also specify rules for handling data and determining outcome. DISCUSSION: Several challenges for study design and execution can be seen in our trial, and it should generate results that will inform and influence the practice of renal replacement therapy in critically ill patients with acute kidney injury. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00004367 ( www.germanctr.de ); 28 May 2013. PMID- 26993264 TI - The real-world prevalence of cardiovascular events related to coronary spasm after percutaneous coronary intervention. AB - BACKGROUND: It is unknown to what extent coronary spasm affects cardiovascular events after percutaneous coronary intervention (PCI) in clinical practice. The aim was to examine the prevalence of cardiovascular events related to coronary spasm following PCI according to stent type. METHODS: We enrolled 933 consecutive patients treated with coronary stent implantation, including bare metal stents (BMS; n=238), first-generation drug-eluting stents (1st DES; n=185), and second generation DES (2nd DES; n=510). We compared stent-oriented endpoints (SOEs; stent thrombosis, target vessel myocardial infarction or unstable angina, target lesion revascularization, and cardiac death) and the differences in SOE related to coronary spasm across stent types. Among the SOEs, spasm-related cardiac event was defined based on JCS guideline. RESULTS: The prevalence of SOE for each stent type was 16.8% (BMS), 16.8% (1st DES), and 7.8% (2nd DES) (p<0.001) and the rates of cardiovascular events related to coronary spasm were 2.9%, 3.2%, and 0.4%, respectively (p=0.005). Multivariate analysis identified the non-use of statin (HR, 0.275, 95% CI, 0.087-0.871, p=0.028) and non-use of 2nd DES (hazard ratio, 0.196, 95% confidence interval, 0.043-0.887, p=0.034) as independent predictors of cardiac events related to coronary spasm. CONCLUSION: The prevalence of cardiovascular events related to coronary spasm was the lowest in patients with 2nd DES. The 2nd DES may be more efficacious and safer from the point of view of the reduction of cardiac events due to coronary spasm during statin therapy. PMID- 26993265 TI - How do we stage acellular mucin in lymph nodes of colorectal cancer specimens without neo-adjuvant therapy? PMID- 26993266 TI - Time to treatment benefit for adult patients with Fabry disease receiving agalsidase beta: data from the Fabry Registry. AB - BACKGROUND: Agalsidase beta is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low alpha-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase beta cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase beta treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase beta. METHODS: The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase beta (average dose 1 mg/kg every 2 weeks) for up to 5 years. RESULTS: The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged >=40 years when agalsidase beta was initiated. CONCLUSIONS: Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase beta 1 mg/kg every 2 weeks. TRIAL REGISTRATION NUMBER: NCT00196742. PMID- 26993267 TI - Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis. AB - BACKGROUND: We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay. METHODS: In 400 patients with these disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis. RESULTS: We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing. CONCLUSIONS: Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype-phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis. PMID- 26993268 TI - Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations. AB - BACKGROUND: Newer approaches to genetic counselling are required for population based testing. We compare traditional face-to-face genetic counselling with a DVD assisted approach for population-based BRCA1/2 testing. METHODS: A cluster randomised non-inferiority trial in the London Ashkenazi Jewish population. INCLUSION CRITERIA: Ashkenazi Jewish men/women >18 years; exclusion criteria: (a) known BRCA1/2 mutation, (b) previous BRCA1/2 testing and (c) first-degree relative of BRCA1/2 carrier. Ashkenazi Jewish men/women underwent pre-test genetic counselling prior to BRCA1/2 testing in the Genetic Cancer Prediction through Population Screening trial (ISRCTN73338115). Genetic counselling clinics (clusters) were randomised to traditional counselling (TC) and DVD-based counselling (DVD-C) approaches. DVD-C involved a DVD presentation followed by shorter face-to-face genetic counselling. Outcome measures included genetic testing uptake, cancer risk perception, increase in knowledge, counselling time and satisfaction (Genetic Counselling Satisfaction Scale). Random-effects models adjusted for covariates compared outcomes between TC and DVD-C groups. One-sided 97.5% CI was used to determine non-inferiority. SECONDARY OUTCOMES: relevance, satisfaction, adequacy, emotional impact and improved understanding with the DVD; cost-minimisation analysis for TC and DVD-C approaches. RESULTS: 936 individuals (clusters=256, mean-size=3.6) were randomised to TC (n=527, clusters=134) and DVD C (n=409, clusters=122) approaches. Groups were similar at baseline, mean age=53.9 (SD=15) years, women=66.8%, men=33.2%. DVD-C was non-inferior to TC for increase in knowledge (d=-0.07; lower 97.5% CI=-0.41), counselling satisfaction (d=-0.38, 97.5% CI=1.2) and risk perception (d=0.08; upper 97.5% CI=3.1). Group differences and CIs did not cross non-inferiority margins. DVD-C was equivalent to TC for uptake of genetic testing (d=-3%; lower/upper 97.5% CI -7.9%/1.7%) and superior for counselling time (20.4 (CI 18.7 to 22.2) min reduction (p<0.005)). 98% people found the DVD length and information satisfactory. 85-89% felt it improved their understanding of risks/benefits/implications/purpose of genetic testing. 95% would recommend it to others. The cost of genetic counselling for DVD-C=L7787 and TC=L17 307. DVD-C resulted in cost savings=L9520 (L14/volunteer). CONCLUSIONS: DVD-C is an effective, acceptable, non-inferior, time-saving and cost-efficient alternative to TC. TRIAL REGISTRATION NUMBER: ISRCTN 73338115. PMID- 26993269 TI - CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma. AB - BACKGROUND: In previous investigation, we reported that stably knocking down cyclin-dependent kinase 4(CDK4) induced expression of let-7c, which further suppressed cell cycle transition and cell growth by modulating cell cycle signaling in nasopharyngeal carcinoma (NPC). In this study, we further explored the molecular function and mechanism of CDK4 modulating miRNAs to stimulate cell cycle transition, cell growth, and Cisplatin (DDP) -resistance on in NPC. METHODS: We identified changes in miRNAs by miRNA array and real-time PCR and the effect on DDP after knocking down CDK4 in NPC cells. Further, we investigated the molecular mechanisms by which CDK4 modulated miR-15a in NPC. Moreover, we also explored the role of miR-15a and the effect on DDP in NPC. Finally, we analyzed the correlation of miR-15a and CDK4 expression in NPC tissues. RESULTS: In addition to let-7 family members, we observed that upregulated expression of miR 15a was significantly induced in CDK4-suppressed NPC cells. Further, we found that knocking down CDK4 suppressed c-Myc expression, and the latter directly suppressed the expression of miR-15a in NPC. Furthermore, miR-15a as a tumor suppressor antagonized CDK4 repressing cell cycle progression and cell growth in vitro and in vivo and induced the sensitivity of cells to DDP by regulating the c Myc/CCND1/CDK4/E2F1 pathway in NPC. Finally, miR-15a was negatively weak correlated with the expression of CDK4 in NPC. CONCLUSIONS: Our studies demonstrate that CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in NPC. PMID- 26993270 TI - The effect of a specialized dyslexia font, OpenDyslexic, on reading rate and accuracy. AB - A single-subject alternating treatment design was used to investigate the extent to which a specialized dyslexia font, OpenDyslexic, impacted reading rate or accuracy compared to two commonly used fonts when used with elementary students identified as having dyslexia. OpenDyslexic was compared to Arial and Times New Roman in three reading tasks: (a) letter naming, (b) word reading, and (c) nonsense word reading. Data were analyzed through visual analysis and improvement rate difference, a nonparametric measure of nonoverlap for comparing treatments. Results from this alternating treatment experiment show no improvement in reading rate or accuracy for individual students with dyslexia, as well as the group as a whole. While some students commented that the font was "new" or "different", none of the participants reported preferring to read material presented in that font. These results indicate there may be no benefit for translating print materials to this font. PMID- 26993271 TI - Human rights dimensions of food, health and care in children's homes in Kampala, Uganda - a qualitative study. AB - BACKGROUND: More than 14 % of Ugandan children are orphaned and many live in children's homes. Ugandan authorities have targeted adolescent girls as a priority group for nutrition interventions as safeguarding nutritional health before pregnancy can reduce the chance of passing on malnutrition to the offspring and thus future generations. Ugandan authorities have obligations under international human rights law to progressively realise the rights to adequate food, health and care for all Ugandan children. Two objectives guided this study in children's homes: (a) To examine female adolescent residents' experiences, attitudes and views regarding: (i) eating patterns and food, (ii) health conditions, and (iii) care practices; and (b) to consider if the conditions in the homes comply with human rights standards and principles for the promotion of the rights to adequate food, health and care. METHODS: A human rights-based approach guided the planning and conduct of this study. Five children's homes in Kampala were included where focus group discussions were held with girls aged 12 14 and 15-17 years. These discussions were analysed through a phenomenological approach. The conditions of food, health and care as experienced by the girls, were compared with international standards for the realisation of the human rights to adequate food, health and care. RESULTS: Food, health and care conditions varied greatly across the five homes. In some of these the girls consumed only one meal per day and had no access to clean drinking water, soap, toilet paper and sanitary napkins. The realisation of the right to adequate food for the girls was not met in three homes, the realisation of the right to health was not met in two homes, and the realisation of the right to care was not met in one home. CONCLUSIONS: In three of the selected children's homes human rights standards for food, health or care were not met. Care in the children's homes was an important contributing factor for whether standards for the rights to adequate food and health were met. PMID- 26993273 TI - It's Not So Easy to Make Resilience Go Away: Commentary on Infurna and Luthar (2016). AB - A large number of studies have identified trajectories of adjustment following acute and aversive life events. In these studies, a stable trajectory of positive health or resilience is almost always the modal outcome (Bonanno, 2004; Bonanno et al., 2011). Infurna and Luthar (2016, this issue) reported that they replicated findings from two early studies in which trajectories of subjective well-being were identified before and after divorce, widowhood, and unemployment (Galatzer-Levy, Bonanno, & Mancini, 2010; Mancini, Bonanno, & Clark, 2011) and then reanalyzed these data in such a way to conclude a decrease in the prevalence of resilience. In this commentary, we discuss three serious flaws in Infurna and Luthar's claims. First, they did not actually replicate our original analyses. They used different data, time points, and parameters. Second, the model specifications in their reanalyses were not optimal because they increased variance, reduced variability in response to the stressor, and had lower entropy, indicating that their models more poorly captured unique patterns of response. Third, their reanalyses were theoretically uninformative as they minimized both group differences and overall responses to the stressor event and thus failed to identify widely acknowledged populations, such as chronic stress reactivity. PMID- 26993272 TI - Resilience to Major Life Stressors Is Not as Common as Thought. AB - We attempted to replicate findings that "most people are resilient" following three events: spousal loss, divorce, and unemployment. We applied growth mixture models to the same longitudinal data set that has previously been used to assert that resilience is ubiquitous. When using identical model specifications, as in prior studies, we found that resilient trajectories were most common, but the number of trajectories identified was different. When we relaxed two assumptions used in prior studies-that (a) all classes have similar variability in levels of postadversity adjustment and (b) there is no variability in changes within classes-we found that a resilience class was least common. Methodologically, our results show how findings on trajectories of change following major life stressors can vary substantially, depending on statistical model specifications. Conceptually, the results underscore the errors inherent in any categorical statements about "rates of resilience" among individuals confronted with major life stressors. Pragmatically, they underscore the dangers in recommending against prophylactic interventions (on the basis of one method of analyzing longitudinal data) for individuals who have experienced major life stressors. PMID- 26993274 TI - Resilience Has Been and Will Always Be, but Rates Declared Are Inevitably Suspect: Reply to Galatzer-Levy and Bonanno (2016). PMID- 26993275 TI - Social Identities in a Globalized World: Challenges and Opportunities for Collective Action. AB - Globalization-the increasing interconnectedness of societies, economies, and cultures-is a defining feature of contemporary social life. Paradoxically, it underlies both the dynamics of global crises (e.g., rising inequality, climate change) and the possibilities for ameliorating them. In this review, we introduce globalization as a multifaceted process and elaborate its psychological effects with respect to identity, culture, and collective action. Using a social identity approach, we discuss three foci of identification: local culture, globalized Western culture, and humanity in its entirety. Each source of identification is analyzed in terms of its psychological meaning and position vis-a-vis the global power structure. Globalized Western culture forms the basis for an exclusive globalized identity, which privileges only some cultures and ways of life. We conceptualize reactions to its core values in terms of cultural identification and rejection and acceptance of, or opposition to, its global social order. Opposition to this inequitable global order is central to inclusive globalized identities (e.g., identification with humanity). These identities may encourage globally minded collective action, even as more research is needed to address their potential caveats. We consider possibilities for social change and action and conclude that a focused application of psychological science to the study of these issues is overdue. PMID- 26993276 TI - With Eyes Wide Open: How and Why Awareness of the Psychological Immune System Is Compatible With Its Efficacy. AB - Life is full of negative events that threaten our self-worth, and we deploy a wide range of potent psychological strategies-such as dissonance reduction, motivated reasoning, downward comparison, self-serving attribution, and outgroup derogation-to defend our egos. People are highly adept at using these psychological immune system strategies while remaining blind to the fact that they have done so. In fact, prominent voices in the field have suggested that this lack of awareness is a necessary condition for the psychological immune system's efficacy; how else could someone continue to believe a self-serving attribution while being aware that the attribution was generated precisely because it favored him or her? In this article, I outline the argument underlying why awareness might be a threat to the efficacy of the psychological immune system and then closely review the empirical literature for evidence supporting this claim. On the contrary, the data indicate people can and do use these strategies with awareness, intention, and efficacy. I subsequently consider three ways people may achieve the apparent paradox of being aware of their own biased mental processes while also believing the conclusions that result from them. The third of these is a novel conceptual approach to the illusion of objectivity, which highlights the potential for dissociation between the objectivity of our mental processes and of our mental products. Finally, I outline the implications of this work for future theoretical and applied research. PMID- 26993278 TI - Neuroaesthetics: The Cognitive Neuroscience of Aesthetic Experience. AB - The field of neuroaesthetics has gained in popularity in recent years but also attracted criticism from the perspectives both of the humanities and the sciences. In an effort to consolidate research in the field, we characterize neuroaesthetics as the cognitive neuroscience of aesthetic experience, drawing on long traditions of research in empirical aesthetics on the one hand and cognitive neuroscience on the other. We clarify the aims and scope of the field, identifying relations among neuroscientific investigations of aesthetics, beauty, and art. The approach we advocate takes as its object of study a wide spectrum of aesthetic experiences, resulting from interactions of individuals, sensory stimuli, and context. Drawing on its parent fields, a cognitive neuroscience of aesthetics would investigate the complex cognitive processes and functional networks of brain regions involved in those experiences without placing a value on them. Thus, the cognitive neuroscientific approach may develop in a way that is mutually complementary to approaches in the humanities. PMID- 26993279 TI - Born Pupils? Natural Pedagogy and Cultural Pedagogy. AB - The theory of natural pedagogy is an important focus of research on the evolution and development of cultural learning. It proposes that we are born pupils; that human children genetically inherit a package of psychological adaptations that make them receptive to teaching. In this article, I first examine the components of the package-eye contact, contingencies, infant-directed speech, gaze cuing, and rational imitation-asking in each case whether current evidence indicates that the component is a reliable feature of infant behavior and a genetic adaptation for teaching. I then discuss three fundamental insights embodied in the theory: Imitation is not enough for cumulative cultural inheritance, the extra comes from blind trust, and tweaking is a powerful source of cognitive change. Combining the results of the empirical review with these insights, I argue that human receptivity to teaching is founded on nonspecific genetic adaptations for social bonding and social learning and acquires its species- and functionally specific features through the operation of domain-general processes of learning in sociocultural contexts. We engage, not in natural pedagogy, but in cultural pedagogy. PMID- 26993277 TI - Working Memory Maturation: Can We Get at the Essence of Cognitive Growth? AB - The theoretical and practical understanding of cognitive development depends on working memory, the limited information temporarily accessible for such daily activities as language processing and problem solving. In this article, I assess many possible reasons that working memory performance improves with development. A first glance at the literature leads to the weird impression that working memory capacity reaches adult levels during infancy but then regresses during childhood. In place of that unlikely explanation, I consider how infant studies may lead to overestimates of capacity if one neglects supports that the tasks provide, compared with adult-level tasks. Further development of working memory during the school years is also considered. Many investigators have come to suspect that working memory capacity may be constant after infancy because of various factors such as developmental increases in knowledge, filtering out of irrelevant distractions, encoding and rehearsal strategies, and pattern formation. With each of these factors controlled, though, working memory still improves during the school years. Suggestions are made for research to bridge the gap between infant and child developmental research, to understand the focus and control of attention in working memory and how these skills develop, and to pinpoint the nature of capacity and its development from infancy forward. PMID- 26993280 TI - A Closer Look at Social Psychologists' Silver Bullet: Inevitable and Evitable Side Effects of the Experimental Approach. AB - The main advantage of experimental research lies in the possibility of systematically investigating the causal relation between the variables of interest. The well-known advantages result from (a) the possibility to manipulate the independent variable, (b) random assignment of participants to the experimental conditions, and (c) the experimenter's control over the operationalization of the variables and the general experimental setting. We argue that it is exactly these elements that constitute core advantages of experimental research but that are-at the same time-associated with side effects, which are often out of focus when researchers derive theoretical conclusions from their experimental findings. We discuss potential restrictions linked to these core elements of experimental research. Implications for both theory development and research design are discussed. PMID- 26993281 TI - A Comment on Eerland et al. (2016). AB - People imagine criminal behavior in greater detail and ascribe more blame to criminals when a description of a crime is written using the imperfective verb aspect (Hart & Albarracin, 2011, Experiment 3). An initiative to reproduce these findings conducted by Eerland et al. (2016) yielded a lack of replication. Eerland et al. have suggested that the original effect was likely driven by a Type I error produced by methodological aspects of the experiment, including low sample size. Recent conceptual replications of Hart and Albarracin's effect (Sherrill, Eerland, Zwaan, & Magliano, 2015), however, might imply the effect could be contingent on sample characteristics. PMID- 26993282 TI - Corrigendum: Sailing From the Seas of Chaos Into the Corridor of Stability. AB - Lakens, D., & Evers, E. R. K. (2014). Sailing from the seas of chaos into the corridor of stability: Practical recommendations to increase the informational value of studies. Perspectives in Psychological Science, 9, 278-292. doi:10.1177/1745691614528520. PMID- 26993283 TI - Model-based pharmacokinetic analysis of elotuzumab in patients with relapsed/refractory multiple myeloma. AB - Elotuzumab is a humanized immunoglobulin G1 monoclonal antibody in development for the treatment of patients with multiple myeloma who have received one or more prior therapies. In this work, 6958 elotuzumab serum concentrations from 375 patients enrolled in four Phase 1 to 3 clinical trials were used to analyze the pharmacokinetics (PK) of elotuzumab. A population PK model with parallel linear and Michaelis-Menten elimination from the central compartment and limited capacity target-mediated elimination from the peripheral compartment described the elotuzumab concentration-time course. Clearance of elotuzumab increased with increasing body weight and weight-based dosing generated uniform exposures across a range of body weights. Coadministration of lenalidomide/dexamethasone background therapy decreased elotuzumab nonspecific clearance by 35 %. Target mediated elimination of elotuzumab increased with increasing baseline serum M protein, resulting in lower exposure in patients with high baseline serum M protein concentration. Age, race, sex, renal and hepatic function, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, albumin and beta2-microglobulin had less than 20 % effect on model parameters and are unlikely to have clinically meaningful effects. Impact of anti-drug antibodies (ADAs) on the PK of elotuzumab was assessed as an ad hoc analysis. In the majority of ADA-positive patients, immunogenicity started early, was transient and resolved by 2-4 months. Since the majority of patients had ADAs detected early, this resulted in a corresponding transient increase in nonspecific clearance at these time points. Nonspecific clearance appeared to return to baseline at later time points when ADAs were no longer detected. PMID- 26993284 TI - Trauma occurs in social contexts. PMID- 26993285 TI - The meaning of living close to a person with Alzheimer disease. AB - Only a few studies explore the lifeworld of the spouses of persons affected by early-onset Alzheimer disease (AD). The aim of this study is to explore the lifeworld of spouses when their partners are diagnosed with AD, focusing on spouses' lived experience. The study employs an interpretative phenomenological framework. Ten in-depth interviews are performed. The results show that spouses' lifeworld changes with the diagnosis. They experience an imprisoned existence in which added obligations, fear, and worry keep them trapped at home, both physically and mentally. In their longing for freedom, new strategies and attitudes helps the spouses to create an extended "lived space" with their partner. The findings stress the importance of paying attention to the lifeworld of spouses and making clinical recommendations on this basis. Most importantly, the lifeworld perspective has implications for how we understand what care is. We hope to challenge all different healthcare professionals and invite them to discuss the deep meaning of care and the definition of being professional in encounters with vulnerable others from a lifeworld perspective. PMID- 26993287 TI - Disaccharide analysis of chondroitin and heparin from farmed Atlantic salmon. AB - The heparin disaccharides detected in farmed Atlantic salmon (Salmo salar) gills and intestines have, with one exception, been reported in porcine heparin. The relative amounts of disaccharides appear to be very different in the two species. Two chondroitin disaccharides with a proposed essential role in the zebrafish (Danio rerio) development and differentiation are detected in farmed Atlantic salmon. In addition, most of the chondroitin/dermatan sulfate and heparin disaccharides detected here have been reported in zebrafish, in support of the claims of the heparin presence in fish. The same chondroitin/dermatan disaccharides were detected in the bones of bony fishes. The rare disaccharide UA2S-GalNAc that was found in trace amounts in all 5 bony fishes was found in relative high amounts in gills and in significant amounts in intestines. The rare heparin disaccharide UA2S-GlcN was in relative highest amounts both in gills and intestines. In context with our previous reports, this communication suggests that glycosaminoglycans in farmed Atlantic salmon heparin need further studies in order to clarify structure and function. PMID- 26993286 TI - Melatonin promotes development of haploid germ cells from early developing spermatogenic cells of Suffolk sheep under in vitro condition. AB - Promotion of spermatogonial stem cell (SSC) differentiation into functional sperms under in vitro conditions is a great challenge for reproductive physiologists. In this study, we observed that melatonin (10(-7) M) supplementation significantly enhanced the cultured SSCs differentiation into haploid germ cells. This was confirmed by the expression of sperm special protein, acrosin. The rate of SSCs differentiation into sperm with melatonin supplementation was 11.85 +/- 0.93% which was twofold higher than that in the control. The level of testosterone, the transcriptions of luteinizing hormone receptor (LHR), and the steroidogenic acute regulatory protein (StAR) were upregulated with melatonin treatment. At the early stage of SSCs culture, melatonin suppressed the level of cAMP, while at the later stage, it promoted cAMP production. The similar pattern was observed in testosterone content. Expressions for marker genes of meiosis anaphase, Dnmt3a, and Bcl-2 were upregulated by melatonin. In contrast, Bax expression was downregulated. Importantly, the in vitro-generated sperms were functional and they were capable to fertilize oocytes. These fertilized oocytes have successfully developed to the blastula stage. PMID- 26993288 TI - Streptococcus agalactiae infection in cancer patients: a five-year study. AB - Although the highest burden of Streptococcus agalactiae infections has been reported in industrialized countries, studies on the characterization and epidemiology are still limited in developing countries and implementation of control strategies remains undefined. The aim of this retrospective study was to assess the epidemiological, clinical, and microbiological aspects of S. agalactiae infections in cancer patients treated at a Reference Brazilian National Cancer Institute - INCA, Rio de Janeiro, Brazil. We reviewed the clinical and laboratory records of all cancer patients identified as having invasive S. agalactiae disease during 2010-2014. The isolates were identified by biochemical analysis and tested for antimicrobial susceptibility. A total of 263 strains of S. agalactiae were isolated from cancer patients who had been clinically and microbiologically classified as infected. S. agalactiae infections were mostly detected among adults with solid tumors (94 %) and/or patients who have used indwelling medical devices (77.2 %) or submitted to surgical procedures (71.5 %). Mortality rates (in-hospital mortality during 30 days after the identification of S. agalactiae) related to invasive S. agalactiae infections (n = 28; 31.1 %) for the specific category of neoplasic diseases were: gastrointestinal (46 %), head and neck (25 %), lung (11 %), hematologic (11 %), gynecologic (4 %), and genitourinary (3 %). We also found an increase in S. agalactiae resistance to erythromycin and clindamycin and the emergence of penicillin-less susceptible isolates. A remarkable number of cases of invasive infections due to S. agalactiae strains was identified, mostly in adult patients. Our findings reinforce the need for S. agalactiae control measures in Brazil, including cancer patients. PMID- 26993290 TI - Prevalence of antiseptic resistance genes increases in staphylococcal isolates from orthokeratology lens wearers over initial six-month period of use. AB - The purpose of this study was to investigate the prevalence of antiseptic resistance (QAC) genes in staphylococci colonizing periorbital tissues and accessories of orthokeratology (ortho-k) lens wearers over a 6-month period and determine the effect of their presence on minimum inhibitory (MIC) and bactericidal concentrations (MBC) of disinfectants and log reduction of multipurpose contact lens solutions (MPS). Staphylococci were isolated from periorbital tissues and accessories of patients before commencing ortho-k therapy and at two subsequent visits. Presence of QAC genes in 116 S. aureus and 67 CNS isolates was determined by PCR and association with period of ortho-k use determined. MICs and MBCs of staphylococci gene-positive were compared with gene negative strains and the effectiveness of four MPS for rigid contact lenses investigated. S. aureus carriage rates in the conjunctiva decreased significantly from 41.2 % (baseline) to 11.8 % (3-months), and 13.3 % (6-months) (p trend 0.03), while CNS increased from 58.8 %(baseline) to 94.1 % (3-months), and 93.3 % (6-months) (p trend 0.02). Prevalence of qacA/B increased considerably over time (S. aureus: 4.4 % to 15.4 %, CNS: 6.7 % to 25 %), but frequency of smr was relatively stable. Only five CNS isolates harboured qacH. MICs and MBCs of gene positive isolates were significantly increased and three MPS did not achieve a 3 log reduction of many QAC-positive strains. Ortho-k lens wear contributed to changes of staphylococcal carriage rates in the conjunctival sac. Use of MPS containing quaternary ammonium compounds may select for the carriage of organisms harbouring QAC genes, as the low concentration of disinfecting agents is not adequate for killing gene-positive strains. PMID- 26993289 TI - Staphylococcus aureus and Pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes. AB - Cystic fibrosis-related diabetes (CFRD) patients suffer from accelerated rates of pulmonary decline compared to cystic fibrosis (CF) patients with normal glucose tolerance (NGT). However, the mechanisms underlying this difference are unknown. While CFRD is associated with increased respiratory infections, a link between infection and enhanced pulmonary dysfunction remains unclear. The development of glucose intolerance is spectral, resulting in impaired glucose tolerance (IGT) prior to the diagnosis of CFRD. Inclusion of IGT patients within the NGT group may diminish the ability to identify correlations with CFRD. With this in mind, this study aimed to determine if the association between CFRD and respiratory infections is correlated with pulmonary decline. Respiratory cultures from 234 CF patients with confirmed diagnosis of NGT or CFRD were analyzed to measure rates of infection, focusing on the two most prevalent bacteria in CF, Staphylococcus aureus and Pseudomonas aeruginosa. Infection status was correlated with pulmonary function and confounding clinical variables including age, gender, blood glucose levels, and CF transmembrane conductance regulator (CFTR) phenotype were considered in multivariate analyses. CFRD patients, particularly those with extremely high blood glucose levels, were more likely than NGT patients to be co infected with S. aureus and P. aeruginosa, compared to infection with only one pathogen. Co-infection was associated with decreased lung function and increased frequency of pulmonary exacerbations, even after adjustment for confounding variables. Alterations in the microbial community composition, as opposed to the presence of a single pathogen, may account for greater pulmonary decline in CFRD patients. PMID- 26993291 TI - Invasive placental disorders: a prospective US and MRI comparative analysis. AB - BACKGROUND: Invasive placental disorders are potentially life-threatening. Its diagnosis and evaluation of degree of invasiveness is vital in surgical and treatment planning. PURPOSE: To compare the role of various imaging modalities used in current practice for evaluation of invasive placental disorders, and evaluate the validity of certain imaging signs for prediction of invasive placenta. MATERIAL AND METHODS: Twenty-two patients, which were clinically stratified as a risk group for underlying invasive placental abnormality, underwent Doppler sonography and magnetic resonance imaging (MRI). Abnormal placental invasiveness was assessed using various Doppler sonography and MRI signs described in the existing literature. We systematically evaluated the utility of each of these modalities and signs, and compared the roles played by them separately and in combination. All the cases were correlated with surgical and pathological findings. RESULTS: Nine patients had surgical and pathological confirmation of placental adhesive disorders, of which eight were predicted correctly by MRI (true positive) while one was misdiagnosed as normal placenta (false negative). All the nine cases were correctly identified by Doppler sonography. MRI was more accurate in predicting bladder invasion, identifying 5/6 cases. CONCLUSION: Both MRI and Doppler sonography are useful for detection of invasive placental disorders. However, MRI is a better predictor of bladder invasion. PMID- 26993292 TI - Does finger sense predict addition performance? AB - The impact of fingers on numerical and mathematical cognition has received a great deal of attention recently. However, the precise role that fingers play in numerical cognition is unknown. The current study explores the relationship between finger sense, arithmetic and general cognitive ability. Seventy-six children between the ages of 5 and 12 participated in the study. The results of stepwise multiple regression analyses demonstrated that while general cognitive ability including language processing was a predictor of addition performance, finger sense was not. The impact of age on the relationship between finger sense, and addition was further examined. The participants were separated into two groups based on age. The results showed that finger gnosia score impacted addition performance in the older group but not the younger group. These results appear to support the hypothesis that fingers provide a scaffold for calculation and that if that scaffold is not properly built, it has continued differential consequences to mathematical cognition. PMID- 26993293 TI - Gesturing during mental problem solving reduces eye movements, especially for individuals with lower visual working memory capacity. AB - Non-communicative hand gestures have been found to benefit problem-solving performance. These gestures seem to compensate for limited internal cognitive capacities, such as visual working memory capacity. Yet, it is not clear how gestures might perform this cognitive function. One hypothesis is that gesturing is a means to spatially index mental simulations, thereby reducing the need for visually projecting the mental simulation onto the visual presentation of the task. If that hypothesis is correct, less eye movements should be made when participants gesture during problem solving than when they do not gesture. We therefore used mobile eye tracking to investigate the effect of co-thought gesturing and visual working memory capacity on eye movements during mental solving of the Tower of Hanoi problem. Results revealed that gesturing indeed reduced the number of eye movements (lower saccade counts), especially for participants with a relatively lower visual working memory capacity. Subsequent problem-solving performance was not affected by having (not) gestured during the mental solving phase. The current findings suggest that our understanding of gestures in problem solving could be improved by taking into account eye movements during gesturing. PMID- 26993294 TI - Inhibitor of PI3K/Akt Signaling Pathway Small Molecule Promotes Motor Neuron Differentiation of Human Endometrial Stem Cells Cultured on Electrospun Biocomposite Polycaprolactone/Collagen Scaffolds. AB - Small molecules as useful chemical tools can affect cell differentiation and even change cell fate. It is demonstrated that LY294002, a small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, can inhibit proliferation and promote neuronal differentiation of mesenchymal stem cells (MSCs). The purpose of this study was to investigate the differentiation effect of Ly294002 small molecule on the human endometrial stem cells (hEnSCs) into motor neuron-like cells on polycaprolactone (PCL)/collagen scaffolds. hEnSCs were cultured in a neurogenic inductive medium containing 1 MUM LY294002 on the surface of PCL/collagen electrospun fibrous scaffolds. Cell attachment and viability of cells on scaffolds were characterized by scanning electron microscope (SEM) and 3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The expression of neuron-specific markers was assayed by real-time PCR and immunocytochemistry analysis after 15 days post induction. Results showed that attachment and differentiation of hEnSCs into motor neuron-like cells on the scaffolds with Ly294002 small molecule were higher than that of the cells on tissue culture plates as control group. In conclusion, PCL/collagen electrospun scaffolds with Ly294002 have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhances viability and differentiation of hEnSCs into neurons through inhibition of the PI3K/Akt pathway. Thus, manipulation of this pathway by small molecules can enhance neural differentiation. PMID- 26993295 TI - miR-124 Acts as a Tumor Suppressor in Glioblastoma via the Inhibition of Signal Transducer and Activator of Transcription 3. AB - MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the level of miR-124 and signal transducer and activator of transcription 3 (STAT3) in GBM tissues and cells. We further investigated the molecular mechanisms of miR-124 and STAT3 in GBM cell lines U87 and U251. Here, we found that miR-124 expression was downregulated in GBM tissues and U87 and U251 cells (all p < 0.001) but not associated with blood routine (RBC, WBC count, etc.) and liver and renal function indicators (all p > 0.05). By contrast, STAT3 was upregulated. Furthermore, the expression of miR-124 was inversely proportional to that of STAT3 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-124 played a suppressor role in the proliferation of U87 and U251 cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-124 binding to the 3'-UTR regions of STAT3 inhibited the expression of STAT3 in U87 and U251 cells. However, the inhibitor of miR-124 promoted the expression of STAT3 and cell proliferation. In conclusion, our data suggest that miR-124 may have a potential role in treatment of GBM patients and that miR-124 is a novel regulator of invasiveness and tumorigenicity in GBM cells by targeting STAT3. The miR 124/STAT3 pathway may be a useful therapeutic agent in GBM patients. PMID- 26993297 TI - Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice. AB - This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n = 24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD + hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-alpha and IL-1beta levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-kappaB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p < 0.05). The surgery also increased the contents of TNF-alpha, IL 1beta, and NF-kappaB activity at all time points after surgery (p < 0.05). The introduction of hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p < 0.05). Moreover, such treatment also decreased TNF-alpha and IL-1beta levels and NF-kappaB activity (p < 0.05). In addition, cell necrosis in the hippocampus induced by hepatectomy was also rescued by hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-kappaB activity in the hippocampus and reducing inflammatory response. PMID- 26993296 TI - Kainic Acid Induces mTORC1-Dependent Expression of Elmo1 in Hippocampal Neurons. AB - Epileptogenesis is a process triggered by initial environmental or genetic factors that result in epilepsy and may continue during disease progression. Important parts of this process include changes in transcriptome and the pathological rewiring of neuronal circuits that involves changes in neuronal morphology. Mammalian/mechanistic target of rapamycin (mTOR) is upregulated by proconvulsive drugs, e.g., kainic acid, and is needed for progression of epileptogenesis, but molecular aspects of its contribution are not fully understood. Since mTOR can modulate transcription, we tested if rapamycin, an mTOR complex 1 inhibitor, affects kainic acid-evoked transcriptome changes. Using microarray technology, we showed that rapamycin inhibits the kainic acid-induced expression of multiple functionally heterogeneous genes. We further focused on engulfment and cell motility 1 (Elmo1), which is a modulator of actin dynamics and therefore could contribute to pathological rewiring of neuronal circuits during epileptogenesis. We showed that prolonged overexpression of Elmo1 in cultured hippocampal neurons increased axonal growth, decreased dendritic spine density, and affected their shape. In conclusion, data presented herein show that increased mTORC1 activity in response to kainic acid has no global effect on gene expression. Instead, our findings suggest that mTORC1 inhibition may affect development of epilepsy, by modulating expression of specific subset of genes, including Elmo1, and point to a potential role for Elmo1 in morphological changes that accompany epileptogenesis. PMID- 26993298 TI - Involvement of FMRP in Primary MicroRNA Processing via Enhancing Drosha Translation. AB - Fragile X mental retardation protein (FMRP), associated with fragile X syndrome, is known as an RNA-binding protein to regulate gene expression at post transcriptional level in the brain. FMRP is also involved in microRNA (miRNA) biogenesis during the process of precursor miRNA (pre-miRNA) into mature miRNA. However, there is no description of the effect of FMRP on primary miRNA (pri miRNA) processing. Here, we uncover a novel role of FMRP in pri-miRNA processing via controlling Drosha translation. We show that the expression of DROSHA protein, instead of its messenger RNA (mRNA) transcripts, is downregulated in both the hippocampus of Fmr1-knockout mice and the FMRP-knockdown Neuro-2a cells. Overexpression or knockdown FMRP does not alter Drosha mRNA stability. Immunoprecipitation and polysome analyses demonstrate that FMRP binds to the Drosha mRNA and enhances its translation. Additionally, we show that loss of FMRP in Fmr1-deficient mice results in the accumulation of three in six analyzed pri miRNAs and the reduction of the corresponding pre-miRNAs and mature miRNAs. Thus, our data suggest that FMRP is involved in pri-miRNA processing via enhancing DROSHA expression that may play an important role in fragile X syndrome. PMID- 26993299 TI - MicroRNA-27a Promotes Inefficient Lysosomal Clearance in the Hippocampi of Rats Following Chronic Brain Hypoperfusion. AB - Chronic brain hypoperfusion (CBH) induces the accumulation of abnormal cellular proteins, accompanied by cognitive decline, and the autophagic-lysosomal system is abnormal in dementia. Whether CBH accounts for autophagic-lysosomal neuropathology remains unknown. Here, we show that CBH significantly increased the number of autophagic vacuoles (AVs) with high LC3-II levels, but decreased SQSTM1 and cathepsin D levels in the hippocampi of rats following bilateral common carotid artery occlusion (2VO) for 2 weeks. Further studies showed that microRNA-27a (Mir27a) was upregulated at 2 weeks compared with the sham group. Additionally, LAMP-2 proteins were downregulated by Mir27a overexpression, upregulated by Mir27a inhibition, and unchanged by binding-site mutations or miR masks, indicating that lamp-2 is the target of Mir27a. Knockdown of endogenous Mir27a prevented the reduction of LAMP-2 protein expression as well as the accumulation of AVs in the hippocampi of 2VO rats. Overexpression of Mir27a induced, while the knockdown of Mir27a reduced, the accumulation of AVs and the LC3-II level in cultured neonatal rat neurons. The results revealed that CBH in rats at 2 weeks could induce inefficient lysosomal clearance, which is regulated by the Mir27a-mediated downregulation of LAMP-2 protein expression. These findings provide an insight into a novel molecular mechanism of autophagy at the miRNA level. PMID- 26993300 TI - Antidepressant-Like Effect of Ropren(r) in beta-Amyloid-(25-35) Rat Model of Alzheimer's Disease with Altered Levels of Androgens. AB - This study elucidated the potential antidepressant-like effect of prolonged Ropren(r) administration (8.6 mg/kg, orally, once daily for 28 days) using a beta amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of beta amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5 mg/kg, subcutaneous, once daily, 28 days) supplementation. Ropren(r) was administered to the GDX rats and GDX rats treated with TP. Depression-like behavior was assessed in the forced swimming test, and the spontaneous locomotor activity was assessed using the open-field test. The corticosterone and testosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with Ropren(r) significantly decreased the immobility time of GDX rats with beta-amyloid (25-35) in the forced swimming test. Coadministration of Ropren(r) with TP exerted a markedly synergistic antidepressant-like effect in the GDX rats with beta-amyloid (25-35 on the same model of depression-like behavior testing. Ropren(r) administered alone or together with TP significantly enhanced crossing, frequency of rearing, and grooming of the GDX rats with beta-amyloid (25-35) in the open-field test. Moreover, Ropren(r) administered alone or together with TP significantly decreased the elevated corticosterone levels in the blood serum of GDX rats with beta-amyloid (25-35) following the forced swimming test. These results indicate that Ropren(r) has a marked antidepressant-like effect in the experimental model of Alzheimer's disease in male rats with altered levels of androgens. PMID- 26993301 TI - Resveratrol and Alzheimer's Disease: Mechanistic Insights. AB - Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by progressive cognitive and memory deficits. The pathological hallmarks of AD include extracellular senile plaques and intracellular neurofibrillary tangles. Although several mechanisms have been used to explain the underlying pathogenesis of AD, current treatment regimens remain inadequate. The neuroprotective effects of the polyphenolic stilbene resveratrol (3,5,4' trihydroxy-trans-stilbene) have been investigated in several in vitro and in vivo models of AD. The current review discusses the multiple potential mechanisms of action of resveratrol on the pathobiology of AD. Moreover, due to the limited pharmacokinetic parameters of resveratrol, multiple strategies aimed at increasing the bioavailability of resveratrol have also been addressed. PMID- 26993305 TI - A case of a ruptured submucosal aneurysm of the small intestine identified using double-balloon enteroscopy. AB - A 47-year-old woman was admitted to our hospital urgently with sudden-onset hematochezia. She was temporarily in a state of hemorrhagic shock. As we strongly suspected bleeding from the small intestine, peroral double-balloon enteroscopy was performed, and indicated a 2.0-cm diameter hemispheric elevated lesion in the jejunum. Moreover, a blood clot was observed at the top of the protrusion. The site was marked by injecting India ink, without taking a biopsy specimen, to avoid further hemorrhaging. Subsequently, laparoscopic partial small bowel resection was performed. On histopathological examination, the lesion was found to be a sac-like submucosal arterial aneurysm, with a diameter of 3.5 mm, comprising several small abnormal arteries. The final diagnosis was a ruptured submucosal aneurysm of the small intestine. Ruptured submucosal aneurysms are very rarely observed in the small intestine. Only a few reports have described their endoscopic findings. Our experience indicates that small bowel enteroscopy may be useful for managing ruptured submucosal aneurysms of the small intestine. PMID- 26993304 TI - Role of Leptin and Orexin-A Within the Suprachiasmatic Nucleus on Anxiety-Like Behaviors in Hamsters. AB - It is well established that the maintenance of energy expenditure is linked to active hypothalamic neural mechanisms controlling adaptive stimuli such as food intake. Variations of glucose levels and hormonal (leptin plus orexin-A) parameters, which are involved with energy homeostasis during different behavioral states, have not yet been fully defined. In this first study, behavioral analyses of an unpredictable stress model dealing with the actions of a sub-chronic administration of orexin-A (ORX-A) and the anti-hunger neuropeptide, i.e., leptin (LEP) within the hypothalamic suprachiasmatic (SCH) nucleus, were conducted on the valuable hibernating rodent (hamster; Mesocricetus auratus) model noted for its distinct depression and anxiety states. Treatment with LEP accounted for a notable reduction (p < 0.01) of body weight in stressed hamsters that not only executed very evident (p < 0.001) movements to and from elevated plus maze (EPM) but also spent less time in the dark area of the light dark box test (LDT). Conversely, ORX-A predominantly evoked anxiogenic effects that were inverted by LEP. Interestingly, the anti-hunger neuropeptide accounted for both down-regulated NPY1 transcripts in mostly lateral-posterior hypothalamic areas while up-regulated levels were detected in the parietal cerebral cortex, hippocampus, and amygdala, which largely behaved in an opposite manner to ORX-A dependent effects. Overall, the present findings corroborate a predominating LEPergic effect of the SCH toward the reduction of hamster anxiety-like behaviors with respect to that of ORX-A signaling, which may constitute useful therapeutic targets for stress-related obesity states. PMID- 26993307 TI - A fully automated and fast method using direct sample injection combined with fused-core column on-line SPE-HPLC for determination of ochratoxin A and citrinin in lager beers. AB - A new fast and sensitive method based on on-line solid-phase extraction on a fused-core precolumn coupled to liquid chromatography with fluorescence detection has been developed for ochratoxin A (OTA) and citrinin (CIT) determination in lager beer samples. Direct injection of 100 MUL filtered beer samples into an on line SPE-HPLC system enabled fast and effective sample extraction including separation in less than 6 min. Preconcentration of OTA and CIT from beer samples was performed on an Ascentis Express RP C18 guard column (5 * 4.6 mm), particle size 2.7 MUm, with a mobile phase of methanol/0.5% aqueous acetic acid pH 2.8 (30:70, v/v) at a flow rate of 2.0 mL min(-1). The flow switch from extraction column to analytical column in back-flush mode was set at 2.0 min and the separation was performed on the fused-core column Ascentis Express Phenyl-Hexyl (100 * 4.6 mm), particle size 2.7 MUm, with a mobile phase acetonitrile/0.5% aqueous acetic acid pH 2.8 in a gradient elution at a flow rate of 1.0 mL min(-1) and temperature of 50 degrees C. Fluorescence excitation/emission detection wavelengths were set at 335/497 nm. The accuracy of the method, defined as the mean recoveries of OTA and CIT from light and dark beer samples, was in the range 98.3-102.1%. The method showed high sensitivity owing to on-line preconcentration; LOQ values were found to be 10 and 20 ng L(-1) for OTA and CIT, respectively. The found values of OTA and CIT in all tested light, dark and wheat beer samples were significantly below the maximum tolerable limits (3.0 MUg kg( 1) for OTA and 2000 MUg kg(-1) for CIT) set by the European Union. PMID- 26993303 TI - Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons. AB - Treatment of brain injury with exosomes derived from mesenchymal stromal cells (MSCs) enhances neurite growth. However, the direct effect of exosomes on axonal growth and molecular mechanisms underlying exosome-enhanced neurite growth are not known. Using primary cortical neurons cultured in a microfluidic device, we found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in MSC-exosomes abolished their effect on axonal growth. Both neuronal cell bodies and axons internalized MSC-exosomes, which was blocked by botulinum neurotoxins (BoNTs) that cleave proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Moreover, tailored MSC-exosomes carrying elevated miR-17-92 cluster further enhanced axonal growth compared to native MSC exosomes. Quantitative RT-PCR and Western blot analysis showed that the tailored MSC-exosomes increased levels of individual members of this cluster and activated the PTEN/mTOR signaling pathway in recipient neurons, respectively. Together, our data demonstrate that native MSC-exosomes promote axonal growth while the tailored MSC-exosomes can further boost this effect and that tailored exosomes can deliver their selective cargo miRNAs into and activate their target signals in recipient neurons. Neuronal internalization of MSC-exosomes is mediated by the SNARE complex. This study reveals molecular mechanisms that contribute to MSC exosome-promoted axonal growth, which provides a potential therapeutic strategy to enhance axonal growth. PMID- 26993306 TI - Ultra-rapid targeted analysis of 40 drugs of abuse in oral fluid by LC-MS/MS using carbon-13 isotopes of methamphetamine and MDMA to reduce detector saturation. AB - The number of oral fluid samples collected by the road policing authority in Victoria, Australia, requiring confirmatory laboratory analysis for drugs proscribed under Victorian legislation (methamphetamine, MDMA and Delta9 tetrahydrocannabinol) has greatly increased in recent years, driving the need for improved analysis techniques to enable expedient results. The aim of this study was to develop an LC-MS/MS-based targeted oral fluid screening technique that covers a broad range of basic and neutral drugs of abuse that can satisfy increased caseload while monitoring other compounds of interest for epidemiological purposes. By combining small sample volume, simple extraction procedure, rapid LC-MS/MS analysis and automated data processing, 40 drugs of abuse including amphetamines, benzodiazepines, cocaine and major metabolites, opioids, cannabinoids and some designer stimulants were separated over 5 min (with an additional 0.5 min re-equilibration time). The analytes were detected using a Sciex(r) API 4500 Q-Trap LC-MS/MS system with positive ESI in MRM mode monitoring three transitions per analyte. The method was fully validated in accordance with international guidelines and also monitored carbon-13 isotopes of MDMA and MA to reduce detector saturation effects, allowing for confirmation of large concentrations of these compounds without the need for dilution or re analysis. The described assay has been successfully used for analysis of oral fluid collected as part of law enforcement procedures at the roadside in Victoria, providing forensic results as well as epidemiological prevalence in the population tested. The fast and reliable detection of a broad range of drugs and subsequent automated data processing gives the opportunity for high throughput and fast turnaround times for forensic toxicology. PMID- 26993309 TI - Synthesis and applications of sulfopropyl ether gamma-cyclodextrin polymer as chiral selector in capillary electrophoresis. AB - A novel sulfopropyl ether gamma-cyclodextrin polymer (SPE-gamma-CDP) through polycondensating sulfated cyclodextrins (SCDs) was synthesized. This synthesis approach also has the potential of preparing other derived cyclodextrins (CDs) polymers. The polymerized SCDs took on both the properties of SCDs and certain characteristics of polymers, such as chiral selectivity and high viscosity. Synthesis parameters, including reactions sequence, sulfation, and polycondensation conditions were investigated systematically. The product was characterized by elemental analysis, infrared spectroscopy (IR), and indirect UV detections prior to use as background electrolytes additive. The separation conditions, including the concentration of SPE-gamma-CDP, the concentration and pH of running buffer, separation voltage, as well as the additional organic solution were optimized during chiral separation of neutral, acidic, and basic enantiomers in capillary electrophoresis (CE). SPE-gamma-CDP was proven to be an effective chiral resolving agent in CE with the advantages of simple synthesis process, low cost, similar ratio of charge-to-mass, low current, great reproducibility, and reusability. Graphical Abstract Synthesis and applications of sulfopropyl ether gamma-cyclodextrin polymer. PMID- 26993308 TI - Fluorescent biosensor for the detection of hyaluronidase: intensity-based ratiometric sensing and fluorescence lifetime-based sensing using a long lifetime azadioxatriangulenium (ADOTA) fluorophore. AB - In this report, we have designed a rapid and sensitive, intensity-based ratiometric sensing as well as lifetime-based sensing probe for the detection of hyaluronidase activity. Hyaluronidase expression is known to be upregulated in various pathological conditions. We have developed a fluorescent probe by heavy labeling of hyaluronic acid with a new orange/red-emitting organic azadioxatriangulenium (ADOTA) fluorophore, which exhibits a long fluorescence lifetime (~20 ns). The ADOTA fluorophore in water has a peak fluorescence lifetime of ~20 ns and emission spectra centered at 560 nm. The heavily ADOTA labeled hyaluronic acid (HA-ADOTA) shows a red shift in the peak emission wavelength (605 nm), a weak fluorescence signal, and a shorter fluorescence lifetime (~4 ns) due to efficient self-quenching and formation of aggregates. In the presence of hyaluronidase, the brightness and fluorescence lifetime of the sample increase with a blue shift in the peak emission to its original wavelength at 560 nm. The ratio of the fluorescence intensity of the HA-ADOTA probe at 560 and 605 nm can be used as the sensing method for the detection of hyaluronidase. The cleavage of the hyaluronic acid macromolecule reduces the energy migration between ADOTA molecules, as well as the degree of self-quenching and aggregation. This probe can be efficiently used for both intensity-based ratiometric sensing as well as fluorescence lifetime-based sensing of hyaluronidase. The proposed method makes it a rapid and sensitive assay, useful for analyzing levels of hyaluronidase in relevant clinical samples like urine or plasma. Graphical Abstract Scheme showing cleavage of HA-ADOTA probe by hyaluronidase and the change in the emission spectrum of HA-ADOTA probe before and after cleavage by hyaluronidase. PMID- 26993302 TI - Insulin-Like Growth Factor-II/Cation-Independent Mannose 6-Phosphate Receptor in Neurodegenerative Diseases. AB - The insulin-like growth factor II/mannose 6-phosphate (IGF-II/M6P) receptor is a multifunctional single transmembrane glycoprotein. Recent studies have advanced our understanding of the structure, ligand-binding properties, and trafficking of the IGF-II/M6P receptor. This receptor has been implicated in a variety of important cellular processes including growth and development, clearance of IGF II, proteolytic activation of enzymes, and growth factor precursors, in addition to its well-known role in the delivery of lysosomal enzymes. The IGF-II/M6P receptor, distributed widely in the central nervous system, has additional roles in mediating neurotransmitter release and memory enhancement/consolidation, possibly through activating IGF-II-related intracellular signaling pathways. Recent studies suggest that overexpression of the IGF-II/M6P receptor may have an important role in regulating the levels of transcripts and proteins involved in the development of Alzheimer's disease (AD)-the prevalent cause of dementia affecting the elderly population in our society. It is reported that IGF-II/M6P receptor overexpression can increase the levels/processing of amyloid precursor protein leading to the generation of beta-amyloid peptide, which is associated with degeneration of neurons and subsequent development of AD pathology. Given the significance of the receptor in mediating the transport and functioning of the lysosomal enzymes, it is being considered for therapeutic delivery of enzymes to the lysosomes to treat lysosomal storage disorders. Notwithstanding these results, additional studies are required to validate and fully characterize the function of the IGF-II/M6P receptor in the normal brain and its involvement in various neurodegenerative disorders including AD. It is also critical to understand the interaction between the IGF-II/M6P receptor and lysosomal enzymes in neurodegenerative processes, which may shed some light on developing approaches to detect and prevent neurodegeneration through the dysfunction of the receptor and the endosomal-lysosomal system. PMID- 26993314 TI - Severe early basal ganglia hypometabolism in neurodegeneration with brain iron accumulation. PMID- 26993310 TI - Segmental quantitative myocardial perfusion with PET for the detection of significant coronary artery disease in patients with stable angina. AB - PURPOSE: The goal of this study is to determine the technical accuracy of segmental perfusion parameters assessed with quantitative cardiac PET imaging in the evaluation of coronary artery disease (CAD) in patients with stable angina. METHODS: A cohort of patients who participated in the EVINCI protocol underwent an evaluation of coronary anatomy by invasive coronary angiography (ICA) and/or coronary computed tomography angiography (CCTA) and PET myocardial perfusion imaging with H2 (15)O, (13)NH3 or (82)Rb. PET studies were analyzed by two independent observers blinded to clinical and instrumental data, and classified as positive or negative for significant CAD using only segmental perfusion measurements and cut-off values from literature. RESULTS: On a per-patient basis, the overall inter-observer agreement on PET results was 90 % (kappa = 0.79), indicating substantial agreement. On a per-vessel basis, the inter-observer agreement on PET results was 88 % (kappa = 0.74) in the RCA territory, 94 % (kappa = 0.84) in the LAD territory and 94 % (kappa = 0.85) in the LCX territory. Segmental PET measurements correctly identified 85 % of the patients, resulting in a global sensitivity of 86 %, a specificity of 84 %, a positive predictive value (PPV) of 69 % and a negative predictive value (NPV) of 93 %. In vessel based analyses, quantitative perfusion parameters had a sensitivity, specificity, PPV and NPV of 92 %, 82 %, 42 % and 99 %, respectively, for the detection of significant coronary stenoses in all major coronary arteries. CONCLUSIONS: The assessment of absolute myocardial perfusion parameters measured at a segment level lead to reliable and accurate identification of patients with significant coronary stenosis at ICA and/or CCTA. PMID- 26993315 TI - Detection of recurrent prostate cancer lesions before salvage lymphadenectomy is more accurate with (68)Ga-PSMA-HBED-CC than with (18)F-Fluoroethylcholine PET/CT. AB - AIM: [(68)Ga]PSMA-HBED-CC ((68)Ga-PSMA) is a novel and promising tracer for highly sensitive combined integrated positron emission tomography and X-ray computed tomography (PET/CT) diagnosis of recurrent prostate cancer (PCA). Our aim was to assess the sensitivity, specificity, positive and negative predictive value (PPV/NPV), and accuracy per lesion, as well as the positive predictive value per patient of (68)Ga-PSMA PET/CT using post-lymphadenectomy histology as a standard, and to compare these values to those obtained in a patient collective scanned using (18)F-Fluoroethylcholine ((18)FEC) PET/CT. METHODS: Thirty eight patients had (18)FEC and 28 patients had (68)Ga-PSMA. We performed a pelvic and/or retroperitoneal lymphadenectomy, if necessary supplemented by resection of locally recurrent lesions in accordance with imaging results. RESULTS: In 30/38 (18)FEC and 23/28 (68)Ga-PSMA patients >=1 focus of PCA was identified in postsurgical histology, leading to a per-patient PPV of 78.9 % for (18)FEC and 82.1 % for (68)Ga-PSMA. In (18)FEC and (68)Ga-PSMA patients, a total of 378 and 308 lymph nodes and local lesions were removed, respectively. For (18)FEC and (68)for Ga-PSMA, the respective sensitivity (95 % confidence interval) was 71.2 % (64.5-79.6 %) and 86.9 % (75.8-94.2 %), specificity was 86.9 % (82.3-90.6 % ) and 93.1 % (89.2-95.9 %), PPV was 67.3 % (57.7-75.9 %) and 75.7 % (64.0-98.5 %), NPV was 88.8 % (84.4-92.3 %) and 96.6 % (93.5-98.5 %), and accuracy was 82.5 % (78.3 86.8 %) and 91.9 % (88.7 %-95.1 %). CONCLUSION: In the present series Ga-PSMA PET/CT shows a better performance than FEC PET/CT with a significantly higher NPV and accuracy for the detection of locoregional recurrent and/or metastatic lesions prior to salvage lymphadenectomy. PMID- 26993316 TI - Human brown adipose tissue [(15)O]O2 PET imaging in the presence and absence of cold stimulus. AB - PURPOSE: Brown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [(15)O]O2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE. METHODS: Seven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [(15)O]O2, [(15)O]H2O, and [(18)F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold. RESULTS: BAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2-47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus. CONCLUSION: Our study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake. PMID- 26993319 TI - Identification of New ATG4B Inhibitors Based on a Novel High-Throughput Screening Platform. AB - Autophagy is an evolutionarily conserved homeostasis process through which aggregated proteins or damaged organelles are enveloped in a double-membrane structure called an autophagosome and then digested in a lysosome-dependent manner. Growing evidence suggests that malfunction of autophagy contributes to the pathogenesis of a variety of diseases, including cancer, viral infection, and neurodegeneration. However, autophagy is a complicated process, and understanding of the relevance of autophagy to disease is limited by lack of specific and potent autophagy modulators. ATG4B, a Cys-protease that cleaves ATG8 family proteins, such as LC3B, is a key protein in autophagosome formation and maturation process. A novel time-resolved fluorescence resonance energy transfer (TR-FRET) assay measuring protease activity of ATG4B was developed, validated, and adapted into a high-throughput screening (HTS) format. HTS was then conducted with a Roche focus library of 57,000 compounds. After hit confirmation and a counterscreen to filter out fluorescence interference compounds, 267 hits were confirmed, constituting a hit rate of 0.49%. Furthermore, among 65 hits with an IC50 < 50 uM, one compound mimics the LC3 peptide substrate (-TFG-). Chemistry modification based on this particular hit gave preliminary structure activity relationship (SAR) resulting in a compound with a 10-fold increase in potency. This compound forms a stable covalent bond with Cys74 of ATG4B in a 1:1 ratio as demonstrated by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Furthermore, this compound displayed cellular ATG4B inhibition activity. Overall, the novel TR-FRET ATG4B protease assay plus counterscreen assay provides a robust platform to identify ATG4B inhibitors, which would help to elucidate the mechanism of the autophagy pathway and offer opportunities for drug discovery. PMID- 26993318 TI - Regional Comparison of Enteral Nutrition-Related Admission Policies in Skilled Nursing Facilities. AB - BACKGROUND: Nursing home admission policies are one driver of increased and earlier gastrostomy placement, a procedure that is not always medically or ethically indicated among patients needing short-term nutrition support. This important clinical decision should be based upon patient prognosis, goals, and needs. We compared nursing home enteral nutrition-related admission policies in New York City and other regions of the United States. We also explored motivations for these policies. METHODS: We conducted a telephone survey with skilled nursing facility administrators in New York City and a random sample of facilities throughout the United States about enteral nutrition-related admission policies. Survey data were matched with publically available data about facility characteristics from the Centers for Medicare and Medicaid Services. The relationship between facility location and admission policies was described with regression models. Reasons for these policies were thematically analyzed. RESULTS: New York City nursing homes were significantly less likely to admit patients with nasogastric feeding tubes than were nursing homes nationwide, after we controlled for facility characteristics (odds ratio = 0.111; 95% CI, 0.032 0.344). Reasons for refusing nasogastric tubes fell into 5 categories: safety, capacity, policy, perception of appropriate level of care, and patient quality of life. CONCLUSION: Our findings indicate that enteral nutrition-related admission policies vary greatly between nursing homes in New York City and nationwide. Many administrators cited safety and policy as factors guiding their institutional policies and practices, despite a lack of evidence. This gap in research, practice, and policy has implications for quality and cost of care, length of hospital stay, and patient morbidity and mortality. PMID- 26993317 TI - PET/MRI in pancreatic and periampullary cancer: correlating diffusion-weighted imaging, MR spectroscopy and glucose metabolic activity with clinical stage and prognosis. AB - PURPOSE: To correlate the clinical stage and prognosis of pancreatic or periampullary cancer with the imaging biomarkers on diffusion-weighted imaging, magnetic resonance spectroscopy and glucose metabolic activity derived from integrated PET/MRI. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained. The study group comprised 60 consecutive patients with pancreatic or periampullary cancer who underwent PET/MRI before treatment. The imaging biomarkers were the minimal apparent diffusion coefficient (ADCmin), choline levels, standardized uptake values, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the tumours. The relationships between these biomarkers and clinical TNM stage were evaluated using the Pearson test and the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUROC) was used to evaluate accuracy. The correlation between the imaging biomarker and progression-free survival (PFS) was investigated using the Cox proportional hazards model. RESULTS: ADCmin was significantly lower in N1 and TNM stage 3+ tumours. Choline levels significantly higher in T4 tumours. TLG was significantly higher in T4, N1 and TNM stage 3+ tumours. MTV was significantly higher in T4, N1, M1, and TNM stage 3+ tumours (all P < 0.05). The MTV/ADCmin ratio exhibited the highest AUROC for predicting T4, N1, M1, and advanced TNM stages tumours, and was an independent predictor of PFS (P = 0.018) after adjustment for age, sex, tumour size and stage. CONCLUSION: The imaging biomarkers from integrated PET/MRI may predict clinical stage and PFS in patients with pancreatic or periampullary cancer. PMID- 26993320 TI - Small-Activating RNA Can Change Nucleosome Positioning in Human Fibroblasts. AB - RNA activation (RNAa) is a mechanism of positive gene expression regulation mediated by small-activating RNAs (saRNAs), which target gene promoters and have been used as tools to manipulate gene expression. Studies have shown that RNAa is associated with epigenetic modifications at promoter regions; however, it is unclear whether these modifications are the cause or a consequence of RNAa. In this study, we examined changes in nucleosome repositioning and the involvement of RNA polymerase II (RNAPII) in this process. We screened saRNAs for OCT4 (POU5F1), SOX2, and NANOG, and identified several novel saRNAs. We found that nucleosome positioning was altered after saRNA treatment and that the formation of nucleosome-depleted regions (NDRs) contributed to RNAa at sites of RNAPII binding, such as the TATA box, CpG islands (CGIs), proximal enhancers, and proximal promoters. Moreover, RNAPII appeared to be bound specifically to NDRs. These results suggested that changes in nucleosome positions resulted from RNAa. We thus propose a hypothesis that targeting promoter regions using exogenous saRNAs can induce the formation of NDRs, exposing regulatory binding sites to recruit RNAPII, a key component of preinitiation complex, and leading to increased initiation of transcription. PMID- 26993321 TI - Antigen Selection for Enhanced Affinity T-Cell Receptor-Based Cancer Therapies. AB - Evidence of adaptive immune responses in the prevention of cancer has been accumulating for decades. Spontaneous T-cell responses occur in multiple indications, bringing the study of de novo expressed cancer antigens to the fore and highlighting their potential as targets for cancer immunotherapy. Circumventing the immune-suppressive mechanisms that maintain tumor tolerance and driving an antitumor cytotoxic T-cell response in cancer patients may eradicate the tumor or block disease progression. Multiple strategies are being pursued to harness the cytotoxic potential of T cells clinically. Highly promising results are now emerging. The focus of this review is the target discovery process for cancer immune therapeutics based on affinity-matured T-cell receptors (TCRs). Target cancer antigens in the context of adoptive cell transfer technologies and soluble biologic agents are discussed. To appreciate the impact of TCR-based technology and understand the TCR discovery process, it is necessary to understand key differences between TCR-based therapy and other immunotherapy approaches. The review first summarizes key advances in the cancer immunotherapy field and then discusses the opportunities that TCR technology provides. The nature and breadth of molecular targets that are tractable to this approach are discussed, together with the challenges associated with finding them. PMID- 26993323 TI - Bayesian latent variable models for the analysis of experimental psychology data. AB - In this paper, we address the use of Bayesian factor analysis and structural equation models to draw inferences from experimental psychology data. While such application is non-standard, the models are generally useful for the unified analysis of multivariate data that stem from, e.g., subjects' responses to multiple experimental stimuli. We first review the models and the parameter identification issues inherent in the models. We then provide details on model estimation via JAGS and on Bayes factor estimation. Finally, we use the models to re-analyze experimental data on risky choice, comparing the approach to simpler, alternative methods. PMID- 26993322 TI - Enhancement of PCR Detection Limit by Single-Tube Restriction Endonuclease-PCR (RE-PCR). AB - BACKGROUND: Polymerase chain reaction (PCR) is widely used in biological research and diagnostics because of its high sensitivity and specificity. However, the sensitivity of PCR is strongly influenced by topological characteristics of the template. Supercoiled templates are known to inhibit PCR, whereas linearized forms of the same supercoiled templates facilitate PCR. OBJECTIVES: This study was conducted to compare the PCR efficiency of circular supercoiled DNA templates to their restriction endonuclease (RE)-mediated linearized forms. Additionally, we also evaluated the possibility of RE digestion of the circular supercoiled templates within the complete PCR buffer. METHODS: Following a systematic approach, we demonstrated that circular supercoiled templates could be efficiently linearized by RE in the complete PCR buffer itself. This allowed linearization of circular supercoiled templates and their subsequent amplification in the PCR buffer in a single-tube format. RESULTS: Using this extremely simple RE-PCR approach, we documented up to tenfold increases in detection efficiency of PCR with two different circular supercoiled templates of clinical origin, including an international calibration standard. CONCLUSIONS: This inexpensive and easy approach to increasing PCR sensitivity can be easily adapted to any standard PCR protocol aimed at amplifying circular supercoiled genomes. Apart from its application in the development of sensitive clinical diagnostic PCR assays for a large number of organisms, this method could also prove to be very useful in simplifying the existing protocols for other applications where pre-PCR restriction digestion is required, such as mutation detection, genotyping, and selective template amplification. PMID- 26993324 TI - Interleukin-13 is involved in the formation of liver fibrosis in Clonorchis sinensis-infected mice. AB - Clonorchiasis is a chronic infection disease often accompanied by formation of liver fibrosis. Previous study has identified that Clonorchis sinensis (C. sinensis, Cs) infection and CsRNASET2 (a member of CsESPs) immunization can drive Th2 immune response. IL-13, a multifunctional Th2 cytokine, has been widely confirmed to be profibrotic mediator. We want to determine whether IL-13 is involved in the generation of liver fibrosis during C. sinensis infection. A part of mice were infected with C. sinensis or immunized with CsRNASET2, respectively. Another part of mice were intravenously injected with rIL-13. Liver tissues of C. sinensis-infected mice were stained with hematoxylin-eosin and Masson's trichrome, respectively. The transcriptional levels of collagen-I, collagen-III, alpha-SMA, and TIMP-1 in the livers of infected mice and rIL-13-treated mice were measured by quantitative RT-PCR. Besides, splenocytes of C. sinensis-infected and CsRNASET2-immunized mice were isolated, respectively. The levels of IL-13 in splenocytes were detected by ELISA. Our results displayed that the livers of C. sinensis-infected mice had serious chronic inflammation and collagen deposition. The transcriptional levels of collagen-I, collagen-III, alpha-SMA, and TIMP-1 in the livers of C. sinensis-infected mice were obviously increased. Splenocytes from both C. sinensis-infected and CsRNASET2-immunized mice expressed high levels of IL-13. Moreover, rIL-13 treatment markedly promoted the transcriptional levels of collagen-I, collagen-III, alpha-SMA, and TIMP-1. These data implied that hepatic fibrosis was formed in the livers of C. sinensis-infected mice, and IL-13 induced by C. sinensis infection and CsRNASET2 immunization might favor this progression. PMID- 26993325 TI - The ecological niche of Dermacentor marginatus in Germany. AB - The ixodid tick Dermacentor marginatus (Sulzer, 1776) is endemic throughout southern Europe in the range of 33-51 ( degrees ) N latitude. In Germany, however, D. marginatus was exclusively reported in the Rhine valley and adjacent areas. Its northern distribution limit near Giessen is located at the coordinates 8.32 ( degrees ) E/50.65 ( degrees ) N. Particularly with regard to the causative agents of rickettsioses, tularemia, and Q fever, the observed locations as well as the potential distribution of the vector D. marginatus in Germany are of special interest. Applying a dataset of 118 georeferenced tick locations, the ecological niche for D. marginatus was calculated. It is described by six climate parameters based on temperature and relative humidity and another six environmental parameters including land cover classes and altitude. The final ecological niche is determined by the frequency distributions of these 12 parameters at the tick locations. Main parameters are the mean annual temperature (frequency distribution characterized by the minimum, median, and maximum of 6.1, 9.9, and 12.2 ( degrees )C), the mean annual relative humidity (73.7, 76.7, and 80.9 %), as well as the altitude (87, 240, 1108 m). The climate and environmental niche is used to estimate the habitat suitability of D. marginatus in Germany by applying the BIOCLIM model. Finally, the potential spatial distribution of D. marginatus was calculated and mapped by determining an optimal threshold value of the suitability index, i.e., the maximum of sensitivity and specificity (Youden index). The model performance is expressed by AUC = 0.91. PMID- 26993326 TI - The promising alliance of anti-cancer electrochemotherapy with immunotherapy. AB - Anti-tumor electrochemotherapy, which consists in increasing anti-cancer drug uptake by means of electroporation, is now implanted in about 140 cancer treatment centers in Europe. Its use is supported by the English National Institute for Health and Care Excellence for the palliative treatment of skin metastases, and about 13,000 cancer patients were treated by this technology by the end of 2015. Efforts are now focused on turning this local anti-tumor treatment into a systemic one. Electrogenetherapy, that is the electroporation mediated transfer of therapeutic genes, is currently under clinical evaluation and has brought excitement to enlarge the anti-cancer armamentarium. Among the promising electrogenetherapy strategies, DNA vaccination and cytokine-based immunotherapy aim at stimulating anti-tumor immunity. We review here the interests and state of development of both electrochemotherapy and electrogenetherapy. We then emphasize the potent beneficial outcome of the combination of electrochemotherapy with immunotherapy, such as immune checkpoint inhibitors or strategies based on electrogenetherapy, to simultaneously achieve excellent local debulking anti-tumor responses and systemic anti-metastatic effects. PMID- 26993327 TI - Genetic composition of interspecific potato somatic hybrids and autofused 4x plants evaluated by DArT and cytoplasmic DNA markers. AB - KEY MESSAGE: Using DArT analysis, we demonstrated that all Solanum * michoacanum (+) S. tuberosum somatic hybrids contained all parental chromosomes. However, from 13.9 to 29.6 % of the markers from both parents were lost in the hybrids. Somatic hybrids are an interesting material for research of nucleus-cytoplasm interaction and sources of new nuclear and cytoplasmic combinations. Analyses of genomes of somatic hybrids are essential for studies on genome compatibility between species, its evolution and are important for their efficient exploitation. Diversity array technology (DArT) permits analysis of the composition of nuclear DNA of somatic hybrids. The nuclear genome compositions of 97 Solanum * michoacanum (+) S. tuberosum [mch (+) tbr] somatic hybrids from five fusion combinations and 11 autofused 4x mch were analyzed for the first time based on DArT markers. Out of 5358 DArT markers generated in a single assay, greater than 2000 markers were polymorphic between parents, of which more than 1500 have a known chromosomal location on potato genetic or physical map. DArT markers were distributed along the entire length of 12 chromosomes. We noticed elimination of markers of wild and tbr fusion components. The nuclear genome of individual somatic hybrids was diversified. Mch is a source of resistance to Phytophthora infestans. From 97 mch (+) tbr somatic hybrids, two hybrids and all 11 autofused 4x mch were resistant to P. infestans. The analysis of the structure of particular hybrids' chromosomes indicated the presence of markers from both parental genomes as well as missing markers spread along the full length of the chromosome. Markers specific to chloroplast DNA and mitochondrial DNA were used for analysis of changes within the organellar genomes of somatic hybrids. Random and non-random segregations of organellar DNA were noted. PMID- 26993328 TI - Elucidation of salt-tolerance metabolic pathways in contrasting rice genotypes and their segregating progenies. AB - KEY MESSAGE: Differentially expressed antioxidant enzymes, amino acids and proteins in contrasting rice genotypes, and co-location of their genes in the QTLs mapped using bi-parental population, indicated their role in salt tolerance. Soil salinity is a major environmental constraint limiting rice productivity. Salt-tolerant 'CSR27', salt-sensitive 'MI48'and their extreme tolerant and sensitive recombinant inbred line (RIL) progenies were used for the elucidation of salt stress tolerance metabolic pathways. Salt stress-mediated biochemical and molecular changes were analyzed in the two parents along with bulked-tolerant (BT) and bulked-sensitive (BS) extreme RILs. The tolerant parent and BT RILs suffered much lower reduction in the chlorophyll as compared to their sensitive counterparts. Activities of antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD) and non-enzymatic antioxidant ascorbic acid were much higher in salt-stressed CSR27 and BT RILs than MI48 and BS RILs. Further, the tolerant lines showed significant enhancement in the levels of amino acids methionine and proline in response to salt stress in comparison to the sensitive lines. Similarly, the tolerant genotypes showed minimal reduction in cysteine content whereas sensitive genotypes showed a sharp reduction. Real time PCR analysis confirmed the induction of methionine biosynthetic pathway (MBP) enzymes cystathionine-beta synthase (CbS), S-adenosyl methionine synthase (SAMS), S adenosyl methionine decarboxylase (SAMDC) and serine hydroxymethyl transferase (SHMT) genes in tolerant lines, suggesting potential role of the MBP in conferring salt tolerance in rice variety CSR27. Proteome profiling also confirmed higher expression of SOD, POD and plastidic CbS and other proteins in the tolerant lines, whose genes were co-located in the QTL intervals for salt tolerance mapped in the RIL population. The study signifies integrated biochemical-molecular approach for identifying salt tolerance genes for genetic improvement for stress tolerant rice varieties. PMID- 26993329 TI - Pyrophosphate: fructose-6-phosphate 1-phosphotransferase (PFP) regulates carbon metabolism during grain filling in rice. AB - KEY MESSAGE: Decreased PFPase activity in rice perturbs the equilibration of carbon metabolism during grain filling but has no visible phenotypic effects during the vegetative and reproductive growth stages. Starch is a primary energy reserve for various metabolic processes in plant. Despite much advance has been achieved in pathways involved in starch biosynthesis, information was still lacked for precise regulation related to carbon metabolism during seed filling in rice (Oryza sativa). The objective of this study was to identify and characterize new gene associated with carbon metabolism during grain filling. By screening our chemical mutant pool, two allelic mutants exhibiting floury endosperm were isolated. No visible phenotypic defects were observed during both the vegetative and reproductive growth stages, except for the floury-like endosperm of grains with significantly reduced kernel thickness, 1000-grain weight and total starch content. Map-based cloning revealed that the mutant phenotypes were controlled by a gene encoding pyrophosphate: fructose-6-phosphate 1-phosphotransferase (PFP, EC 2.7.1.90) beta subunit (PFPbeta), which catalyzes reversible interconversion between fructose-6-phosphate and fructose-1, 6-bisphosphate. The identity of PFP beta was further confirmed by a genetic complementation test. Subcellular analysis demonstrated that PFPbeta was localized in cytoplasm. Quantitative PCR and histochemical staining indicated PFP beta was ubiquitously expressed in various tissues. Furthermore, we found PFP beta could express in both the early and late phases of starch accumulation during grain filling and decreased activity of PFP beta in pfp mutants resulted in compromised carbon metabolism with increased soluble sugar contents and unfavorable starch biosynthesis. Our results highlight PFPbeta functions in modulating carbon metabolism during grain filling stage. PMID- 26993330 TI - Challenges to health workers and their opinions about parents' refusal of oral polio vaccination in the Khyber Pakhtoon Khawa (KPK) province, Pakistan. AB - A qualitative study design was adapted to explore the challenges faced by health workers (HWs) during the polio health campaign. In addition, HWs' opinions about the factors causing parents to refuse oral polio vaccination (OPV) were also explored. Four focus group discussions (FGDs) were held (from 1st January 2015 31st March 2015) with the HWs who participated in the OPV campaigns in the polio red zones of Khyber Pakhtoon Khawa (KPK) province of Pakistan, namely Kohat (FG 1), Domel and Bannu (FG 2), Hangoo (FG 3), and Peshawar (FG 4). A total of N=42 HWs (10-11 in each FG) agreed to participate in this study. Overall, HWs disclosed that public attitude and harsh behaviour towards the HWs and security threats are the two main challenges they face. Common issues hindering parents' willingness to vaccinate their children against OPV are: OPV is seen as haram and not permitted in Islam, it is said to contain the blood of pigs (Khinzir) and monkeys, and parents are afraid that it is done to induce sterility among their children. HWs also shared that parents have a strong belief in the conspiracies that are associated with OPV, i.e. the USA and CIA, are spying on us and our government is helping them to achieve their agenda. Furthermore, HWs revealed that frequent visits may further strengthen parents' perceptions and make them more resistant to OPV. The common side effects of OPV reported by parents were mainly gastro-intestinal problems and in some cases mild to moderate fever with some respiratory symptoms. There is a great need to improve the logistics and facilities for HWs assisting in vaccination programmes. Furthermore, it is necessary to improve education, so people understand the basic concept of revaccination and booster doses, thereby assisting in creating a basic understanding of vaccinations, which may trigger changes in attitudes and make people believe in the benefits of OPV rather than following the conspiracies that lead them to refuse it. PMID- 26993331 TI - A phase 1, placebo-controlled, randomized study of the safety, tolerability, and immunogenicity of a Clostridium difficile vaccine administered with or without aluminum hydroxide in healthy adults. AB - INTRODUCTION: Clostridium difficile is a significant cause of morbidity and mortality in hospitals, nursing homes, and long-term care facilities. The bacteria can produce 3 toxins, of which the C. difficile toxin A and C. difficile toxin B are the principal virulence factors for C. difficile-associated disease. METHODS: A phase 1, first-in-human, placebo-controlled, dose-escalation study was performed to assess the safety and immunogenicity of an investigational vaccine candidate consisting of genetically and chemically detoxified, purified toxins A and B. The toxoids, either alone or in combination with aluminum hydroxide (Al(OH)3), were administered to healthy adults 50-85 years of age at antigen dose levels of 50, 100, or 200 MUg in a 3-dose regimen administered at 0, 1, and 6 months. RESULTS: Overall, the C. difficile vaccine formulations and doses administered were generally well tolerated. Local reactions and systemic events were predominantly mild to moderate, were more common in the 50-64-year age cohort, and comprised mostly injection site pain, headache, and fatigue. In subjects who received the vaccine formulations, both the toxin A- and toxin B specific neutralizing antibody geometric mean concentrations increased substantially at 1 month after Dose 2 and after Dose 3 compared to baseline. In the 50-64-year age cohort, geometric mean fold rises (GMFRs) in toxin A-specific neutralizing antibodies from baseline at Month 7 ranged from 59.19 to 149.23 in the vaccine groups compared to 2.47 in the control group. For toxin-B specific neutralizing antibodies, the GMFRs from baseline at Month 7 ranged from 116.67 to 2503.75 in the vaccine groups compared to 2.48 in the control group. In the 65-85 year age cohort, GMFRs in toxin A-specific neutralizing antibodies from baseline at Month 7 ranged from 42.73 to 254.77 in the vaccine groups compared to 2.03 in the control group. For toxin-B specific neutralizing antibodies, the GMFRs from baseline at Month 7 ranged from 136.12 to 4922.80 in the vaccine groups compared to 1.58 in the control group. Potent antitoxin neutralizing responses were still evident in immunized subjects in both age groups at Month 12. Although there was no clear dose-level response pattern, the data suggest that both the antitoxin A- and B-specific neutralizing responses were trending higher in the toxoid-only groups compared to the toxoid+Al(OH)3 groups. Furthermore, the magnitude of the immune response was similar in the 2 age cohorts. CONCLUSION: The vaccine formulations studied in this phase 1 study were immunogenic and well tolerated. The results presented support further development of the C. difficile vaccine candidate in a larger population of subjects to determine the optimal dose and immunization schedule. CLINICAL TRIAL REGISTRY: NCT01706367. PMID- 26993332 TI - Development and antigenic characterization of three recombinant proteins with potential for Glasser's disease prevention. AB - Haemophilus parasuis is the causative agent of Glasser's disease, which causes high morbidity and mortality in piglets, leading to severe economic losses. The lack of a commercial vaccine against a broad spectrum of strains has limited the disease control. H. parasuis outer membrane proteins (OMPs) are potentially essential components for vaccine formulation. In this study, seven putative OMPs were selected from the annotated H. parasuis serovar 5 genome; they were predicted by bioinformatics and annotated as potential virulence-related factors. These proteins were cloned, expressed, and purified as His-tagged proteins. Antigenicity of the candidate proteins was assessed using Western blotting with convalescent sera against H. parasuis serovar 5. The immunogenicity of the seven OMPs was assessed in a guinea pig model. Except VacJ, all the other six recombinant proteins elicited a detectable antibody response. Antisera against four of the selected proteins effectively killed the bacteria in vitro. Three proteins (Omp26, VacJ, and HAPS_0742) were found to confer significant protection against challenge with a lethal dose of H. parasuis in a guinea pig model. The results suggest that these three proteins have a strong potential to be vaccine candidates against Glasser's disease. PMID- 26993333 TI - Status of vaccine research and development of vaccines for malaria. AB - Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. PMID- 26993334 TI - A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus. AB - Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus-host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (-/-) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model, a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPs). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (-/-) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (-/-) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen. PMID- 26993335 TI - Status of vaccine research and development of vaccines for HIV-1. AB - Human immunodeficiency virus (HIV) is the cause of one of the most lethal pandemics in human history, although in recent years access to highly effective anti-retroviral therapy has provided new hope worldwide. Transmission of HIV by sexual contact, childbirth and injection drug use has been reduced, but 2 million are newly infected each year, and much of the transmission is from people who do not know their status. In addition to known methods, a preventive vaccine is needed to end the pandemic. The extraordinary mutability and genetic diversity of HIV is an enormous challenge, but vaccines are being designed for broad coverage. Computer-aided design of mosaic immunogens, incorporating many epitopes from the entire genome or from conserved regions aim to induce CD8+ T cells to kill virus infected cells or inhibit virus replication, while trimeric envelope proteins or synthetic mimics aim to induce broadly reactive neutralizing antibodies similar to those cloned from some infected patients. Induction of more potent and durable responses may require new adjuvants or replicating chimeric vectors chimeras that bear HIV genes. Passive or genetic delivery of broadly neutralizing antibodies may provide broad protection and/or lead to insights for vaccine designers. Proof of-concept trials in non-human primates and in one human efficacy trial have provided scientific clues for a vaccine that could provide broad and durable protection against HIV. The use of vaccines to destroy HIV reservoirs as part of therapy or cure is now also being explored. PMID- 26993336 TI - Report from the World Health Organization's Product Development for Vaccines Advisory Committee (PDVAC) meeting, Geneva, 7-9th Sep 2015. AB - There are more vaccines in development, against a greater number of pathogens, than ever before. A challenge with this exceptional level of activity and investment is how to select and resource the most promising approaches to have the most significant impact on public health. The WHO Product Development for Vaccines Advisory Committee (PDVAC) was established in 2014 to provide strategic advice and recommendations to WHO for vaccines in clinical development that could have a significant impact on public health in low and middle income countries. On 7-9th September 2015, PDVAC was convened for the second time, when the committee reviewed vaccine developments in 24 disease areas. This report summarises the key recommendations from that consultation. PMID- 26993337 TI - Impact of oral cholera vaccines in cholera-endemic countries: A mathematical modeling study. AB - BACKGROUND: Impact evaluation of vaccination programs is necessary for making decisions to introduce oral cholera vaccines (OCVs) in cholera-endemic countries. METHODS: We analyzed data to forecast the future global burden of cholera. We developed a mathematical model of cholera transmission in three countries as examples: Nigeria, Uganda, and Indonesia. After fitting the model, we evaluated the impact of OCVs delivered in four vaccination strategies varying by target age group and frequency of vaccination over the period of 2015-2030. RESULTS: Data suggest that the global annual incidence of cholera will increase from 3046238 in 2015 to 3787385 in 2030 with the highest burden in Asia and Africa where overall population size is large and the proportion of population with access to improved sanitation facilities is low. We estimate that OCV will reduce the cumulative incidence of cholera by half in Indonesia and >80% in Nigeria and Uganda when delivered to 1+ year olds every three years at a coverage rate of 50%, although cholera may persist through higher coverage rates (i.e., >90%). The proportion of person-to-person transmission compared to water-to-person transmission is positively correlated with higher vaccination impact in all three countries. CONCLUSIONS: Periodic OCV vaccination every three or five years can significantly reduce the global burden of cholera although cholera may persist even with high OCV coverage. Vaccination impact will likely vary depending on local epidemiological conditions including age distribution of cases and relative contribution of different transmission routes. PMID- 26993338 TI - Oropharyngeal exercises in the treatment of obstructive sleep apnoea: our experience. AB - INTRODUCTION: Oropharyngeal exercises are new, non-invasive, cost effective treatment modality for the treatment of mild to moderate obstructive sleep apnoea. It acts by increasing the tone of pharyngeal muscles, is more physiological, and effects are long lasting. AIM OF THE STUDY: The aim of our present study was to evaluate the effect of oropharyngeal exercises in the treatment of mild to moderate obstructive sleep apnoea. METHOD: Twenty patients of mild to moderate obstructive sleep apnoea syndrome (OSAS) were given oropharyngeal exercise therapy for 3 months divided into three phases in graded level of difficulty. Each exercise had to be repeated 10 times, 5 sets per day at their home. Oropharyngeal exercises were derived from speech-language pathology and included soft palate, tongue, and facial muscle exercises. Anthropometric measurements, snoring frequency, intensity, Epworth daytime sleepiness and Berlin sleep questionnaire, and full polysomnography were performed at baseline and at study conclusion. RESULTS: Body mass index (25.6 +/- 3.1) did not change significantly at the end of the study period. There was significant reduction in the neck circumference (38.4 +/- 1.3 to 37.8 +/- 1.6) at the end of the study. Significant improvement was seen in symptoms of daytime sleepiness, witnessed apnoea, and snoring intensity. Significant improvement was also seen in sleep indices like minimum oxygen saturation, time duration of Sao2 < 90 %, sleep efficiency, arousal index, and total sleep time N3 stage of sleep at the end of study. CONCLUSION: Graded oropharyngeal exercise therapy increases the compliance and also reduces the severity of mild to moderate OSAS. PMID- 26993339 TI - Adiponectin protects the kidney against chronic intermittent hypoxia-induced injury through inhibiting endoplasmic reticulum stress. AB - PURPOSE: The current study was carried out to assess the effects of chronic intermittent hypoxia (CIH) on the kidney, the intervention roles of adiponectin (Ad), and the associated mechanisms. METHODS: Sixty Wistar rats were randomly divided into four groups: the normal control (NC), normal control plus Ad supplement (NC + Ad), CIH, and CIH plus Ad supplement (CIH + Ad) groups. The rats in both CIH and CIH + Ad groups were submitted to a CIH environment for 4 months, while the rats in NC and NC + Ad groups were housed with the normal air for 4 months. In addition, the rats in NC + Ad and CIH + Ad groups were treated with an intravenous injection of Ad at a dosage of 10 MUg per injection, twice a week, for four successive months. RESULTS: The production level of reactive oxygen species (ROS) and the protein levels of endoplasmic reticulum (ER) stress, as well as the cell apoptosis level in kidney, were all higher in the CIH group than in the NC and NC + Ad groups (all p < 0.05). However, the ROS production, the protein of ER stress, and cell apoptosis levels in kidney were all lower in the CIH + Ad group than those in the CIH group (all p < 0.05). CONCLUSION: Ad could protect against CIH-induced renal cell apoptosis through inhibiting ROS-related ER stress. PMID- 26993341 TI - Nocturnal systolic blood pressure is increased in restless legs syndrome. AB - PURPOSE: Restless legs syndrome (RLS) is a frequent sensorimotor disorder characterized by an urge to move the legs, with symptoms appearing during the night and disturbing nocturnal sleep. There is a growing body of evidence that RLS correlates with an increased risk of cardiovascular diseases and hypertension. The aim of this study was to test the hypothesis that patients with RLS have higher blood pressure (BP) during the night than people without RLS. METHODS: We have analyzed polysomnographic (PSG) recordings of 30 patients with RLS and 27 subjects without the sleep disorder. During PSG, beat-to-beat BP measurement was performed. RESULTS: Patients with RLS have higher nocturnal and sleep-time systolic blood pressure compared to controls (124.4 vs. 116.5 mmHg, p < 0.05; 123.5 vs. 116.1 mmHg, p < 0.05). There was no noticeable dip in the values of nocturnal systolic pressure of patients with RLS. CONCLUSIONS: Our results support the hypothesis that RLS and hypertension are linked. Thus, we believe patients with RLS require close observation with regard to cardiovascular risk factors. PMID- 26993340 TI - Prevalence of potential nonallergic rhinitis at a community-based sleep medical center. AB - PURPOSE: Nonallergic rhinitis (NAR) is a common condition involving symptomatic nasal congestion, stuffiness, or rhinorrhea, which overlap with symptoms of allergic rhinitis. Scant research has examined NAR and sleep. The aim of this study was to assess the frequency of potential NAR symptoms in a large sample of sleep center patients. METHODS: A retrospective chart review was conducted on 2658 adult patients at our sleep center from 2008 to 2012; 1703 reported clinically relevant nasal congestion. For this subset, potential NAR status (NAR+ vs NAR-) was determined using a brief survey. NAR groups were further divided into three sub-groups based on presenting chief complaints: insomnia (INS), nonrestorative sleep (NRS), and sleep-disordered breathing (SDB). Patients objectively diagnosed with SDB were also analyzed by NAR status. Validated scales for sleepiness, insomnia, anxiety, and depression were compared among the groups. RESULTS: Potential NAR+ comprised 70 % (1194 of 1703) of patients with congestion and showed significantly higher congestion scores than NAR- status [11.97 (3.62) vs 10.47 (3.37); p = .001; g = 0.42; 95 % CI, 0.32-0.53]. The proportion of potential NAR+ cases for each presenting chief complaint was nearly identical (range 69.6 to 71.2 %). However, the comparison of effects between NAR+ and NAR- cases within each presenting group (INS, NRS, SDB) was more consistently significant on the scales for insomnia, sleepiness, anxiety, and depression only in the SDB category. The same four symptoms, measured in those objectively diagnosed with SDB, were also significantly worse in NAR+ compared to NAR- patients. CONCLUSIONS: Regardless of presenting chief complaint and ultimate diagnosis of sleep-disordered breathing, potential nonallergic rhinitis was common in patients at a sleep medical center at a rate possibly greater than twice that reported in the general population. Potential NAR+ was associated with worse sleep and distress symptoms. In both prevalence and treatment studies, research must further evaluate the potential impact of NAR on specific sleep disorders. PMID- 26993342 TI - Effect of CPAP therapy on C-reactive protein and cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome. AB - PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with neurocognitive impairment. We examined the role of the systemic inflammatory response, measured by high-sensitivity C-reactive protein (hsCRP) assay, and the effect of CPAP treatment on hsCRP and cognitive impairment in patients with OSAHS. METHODS: Eligible subjects (n = 178) were categorized into two groups: absent or mild OSAHS, and moderate to severe OSAHS. First, the Montreal Cognitive Assessment (MoCA) and serum hsCRP concentration were measured. Then, the moderate to severe OSAHS group was further divided into a conservative treatment subgroup (n = 68) and a CPAP subgroup (n = 68). After 6 months of treatment, MoCA scores and hsCRP concentrations were re-measured in the moderate to severe group. RESULTS: Compared with the absent or mild OSAHS group, hsCRP concentration was higher (1.00 +/- 1.28 mg/L versus 2.71 +/- 1.8, p < 0.001) and MoCA scores were significantly lower (27.4 +/- 1.4 versus 26.3 +/- 2.0, p < 0.001) in the moderate to severe group. After adjustment for age, education, body mass index, and neck circumference, hsCRP and MoCA scores correlated with parameters of overnight hypoxia. hsCRP and the proportion of time spent with blood oxygen saturation < 90 % (T90) predicted MoCA score. hsCRP and MoCA score improved, and the subdomains of the MoCA were partially improved, in the CPAP treatment subgroup. In conservatively managed patients, hsCRP concentration increased, and there was no improvement in neurocognitive dysfunction, with the memory subdomain significantly worse. CONCLUSIONS: hsCRP may play a role in neurocognitive dysfunction in OSAHS. Long-term CPAP treatment could normalize the serum hsCRP concentration and partially reverse cognitive dysfunction in OSAHS. PMID- 26993343 TI - A method to determine integrated steroid levels in wildlife claws. AB - Glucocorticoids act throughout life to regulate numerous physiological and behavioral processes. Their levels are therefore highly labile, reacting to varying conditions and stressors. Hence, measuring glucocorticoids (and other steroids) in wildlife is challenging, and devising methods that are unaffected by the stress of capture and handling should be explored. Here we use the tip of free-ranging chameleons' claws that were cut to allow individual identification, and report a steroids extraction and quantification method. Claw steroids present an integrated level representing the period of claw growth. We found that we could measure corticosterone in small amounts of chameleon claw matrix using commercial EIA kits. Using this method, we learned that in wild male chameleons, claw corticosterone levels were associated with body size. We suggest that claw testing can potentially provide an ideal matrix for wildlife biomonitoring. PMID- 26993345 TI - Intense pulsed light versus photodynamic therapy using liposomal methylene blue gel for the treatment of truncal acne vulgaris: a comparative randomized split body study. AB - Acne vulgaris is an extremely common skin condition. It often leads to negative psychological consequences. Photodynamic therapy (PDT) using intense pulsed light has been introduced for effective treatment of acne. The objective was to study the effect of PDT in truncal acne vulgaris using liposomal methylene blue (LMB) versus IPL alone. Thirty-five patients with varying degrees of acne were treated with topical 0.1 % LMB hydrogel applied on the randomly selected one side of the back, and after 60 min the entire back was exposed to IPL. The procedure was done once weekly for three sessions and patients were re-evaluated 1 month after the third session by two independent dermatologists. Acne severity was graded using the Burton scale. Patient satisfaction using Cardiff Acne Disability Index (CADI) was recorded before and after treatment. On LMB-pretreated side, inflammatory acne lesion counts were significantly decreased by 56.40 % compared with 34.06 % on IPL alone. Marked improvement was seen on LMB-pretreated side in 11.5 % of patients compared with 2.8 % on IPL alone. There was a correlation between CADI score and overall improvement. Our study concluded that LMB-IPL is more effective than IPL alone, safe with tolerable pain in the treatment of acne vulgaris on the back. LMB-IPL is more effective than IPL alone, safe with tolerable pain in the treatment of acne vulgaris on the back. PMID- 26993344 TI - Sequence-targeted nucleosome sliding in vivo by a hybrid Chd1 chromatin remodeler. AB - ATP-dependent chromatin remodelers regulate chromatin dynamics by modifying nucleosome positions and occupancy. DNA-dependent processes such as replication and transcription rely on chromatin to faithfully regulate DNA accessibility, yet how chromatin remodelers achieve well-defined nucleosome positioning in vivo is poorly understood. Here, we report a simple method for site-specifically altering nucleosome positions in live cells. By fusing the Chd1 remodeler to the DNA binding domain of the Saccharomyces cerevisiae Ume6 repressor, we have engineered a fusion remodeler that selectively positions nucleosomes on top of adjacent Ume6 binding motifs in a highly predictable and reproducible manner. Positioning of nucleosomes by the fusion remodeler recapitulates closed chromatin structure at Ume6-sensitive genes analogous to the endogenous Isw2 remodeler. Strikingly, highly precise positioning of single founder nucleosomes by either chimeric Chd1 Ume6 or endogenous Isw2 shifts phased chromatin arrays in cooperation with endogenous chromatin remodelers. Our results demonstrate feasibility of engineering precise nucleosome rearrangements through sequence-targeted chromatin remodeling and provide insight into targeted action and cooperation of endogenous chromatin remodelers in vivo. PMID- 26993348 TI - Disseminated Renal Burkitt Lymphoma With Malignant Inferior Vena Caval Thrombosis in a Child. AB - The most common causes of renal mass with malignant venous thrombosis are Wilms' tumor and renal cell carcinoma. Although renal involvement may occur in disseminated lymphomas, primary renal Burkitt lymphoma (BL) is rare. Vascular tropism is not a usual feature of lymphoma; thus, primary renal BL with venous extension is distinctly unusual. However, it is important to diagnose this entity because such patients respond well to medical management and may not require surgery. We report a pediatric case of primary renal BL with malignant vascular thrombus and systemic dissemination where biopsy was diagnostic and enabled appropriate treatment. PMID- 26993346 TI - Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease. AB - INTRODUCTION: The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain. METHODS: We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study. RESULTS: We confirm that variation in/near APOE/TOMM40 (P = 6 * 10(-14)) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, P = .0007). We found evidence for risk in/near CR1 (P = 7 * 10(-4)), ABCA7 (P = .02) and BIN1 (P = .04). ORs at variants near INPP5D and NME8 did not overlap between PCA and typical AD. Exploratory genome-wide association studies confirmed APOE and identified three novel loci: rs76854344 near CNTNAP5 (P = 8 * 10(-10) OR = 1.9 [1.5-2.3]); rs72907046 near FAM46A (P = 1 * 10(-9) OR = 3.2 [2.1 4.9]); and rs2525776 near SEMA3C (P = 1 * 10(-8), OR = 3.3 [2.1-5.1]). DISCUSSION: We provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD. PMID- 26993349 TI - Long-term Follow-up of the Virtue Quadratic Male Sling. AB - OBJECTIVE: To report our long-term outcomes of Virtue Quadratic (VQ) sling since male slings have been introduced as a potential alternative treatment option to the artificial urinary sphincter (AUS), with limited long-term data available for proof of efficacy. Herein, we report our data. METHODS: A retrospective review was performed on all Virtue slings performed at our institution over a 2-year period. Patient-reported outcomes regarding procedure success, complications, as well as subsequent procedures were identified. Procedure failure was defined as the inability to reduce patient's preoperative pad use, sling explant for complications, and need for AUS due to continued incontinence. RESULTS: We identified 32 consecutive male patients who were implanted with the VQ sling over the study period. One patient was excluded due to no follow-up. Median follow-up was 55 months. Median preoperative and postoperative pads per day were 3 (interquartile range: 1-3) and 2 (1-2.5). There were 21 (68%) patients who were considered procedure failures. Two (7%) patients reported chronic pain following placement and 7 (22%) underwent subsequent sling explant due to pain or for failure (1 vs 6). Six (20%) patients underwent subsequent AUS placement. Failure was more likely in patients with external beam radiation therapy (6, 19%) (P = .02). There was no association between procedure failure with age (P = .65) or severity of incontinence (P = .17). CONCLUSION: This study demonstrated a significant procedure failure and complication rate with the VQ sling. Thus, we do not recommend the use of the VQ sling and have abandoned all further implantation of the device. PMID- 26993350 TI - Upper and Lower Urinary Tract Endoscopy Training on Thiel-embalmed Cadavers. AB - OBJECTIVE: To evaluate Thiel-embalmed cadavers as a new training model for urological endoscopy procedures. MATERIALS AND METHODS: Twelve urologists performed upper and lower urinary tract endoscopies on 5 different Thiel-embalmed cadavers to evaluate this potentially new training model in urological endoscopic procedural training. Using a 5-point Likert scale, the participants assessed the quality of the tissue and the overall experience of the endoscopy in comparison to a live patient procedure. RESULTS: Thiel-embalmed cadavers have shown to mimic live patient endoscopy of the upper and lower urinary tract in terms of almost identical overall anatomical conditions and manipulation characteristics of the tissue. The mucosa of the urethra and ureters showed similar colors and consistency in comparison to a live patient, whereas bladder mucosa was lacking the visibility of the vessels, thus was unsuitable for identifying any mucosal abnormalities. The flexibility of the muscles allowed for proper patient positioning, whereas the loss of muscle tonus made ureteroscopy more difficult although sufficiently comparable to the procedure done in a live patient. CONCLUSION: Thiel-embalmed cadavers have already been proven to be a suitable training model for several medical procedures. They are known for preserving tissue color, consistency, and flexibility without the irritant odors or risk of infection, which make them resemble live patients with real-life surgical challenges. The results of our study strongly suggest that despite some minor drawbacks, Thiel-embalmed cadavers are a suitable simulation model for initial training of urethrocystoscopy and ureteroscopy. PMID- 26993351 TI - Outpatient Ultrasound Urethrogram for Assessment of Anterior Urethral Stricture: Early Experience. AB - OBJECTIVE: To describe the technique of ultrasound urethrogram (USUG) for the diagnosis of anterior urethral stricture performed in an ambulatory setting without any adjunctive imaging. MATERIALS AND METHODS: Between September 2013 and September 2015, 35 consecutive adult men (>18 years old) presenting for anterior urethral reconstruction underwent outpatient USUG prior to definitive management. No alternative imaging test was performed. Lengths of the strictures as determined by outpatient USUG and via direct intraoperative measurements were compared by a paired t test. RESULTS: Strictures were in the bulbar urethra in 24 men and in the penile urethra in 11 men. The differences between the outpatient USUG length measurements (mean = 1.86 cm) and the intraoperative stricture length measurements (mean = 2.02 cm) were not significantly different (P = .10). Additionally, the correlation coefficient between these length measurements was 0.84 (P < .001). CONCLUSION: Preoperative USUG performed in the ambulatory setting for the diagnosis and characterization of anterior urethral strictures is safe and feasible. This outpatient imaging modality offers an alternative to retrograde urethrogram. PMID- 26993347 TI - The plant secretory pathway seen through the lens of the cell wall. AB - Secretion in plant cells is often studied by looking at well-characterised, evolutionarily conserved membrane proteins associated with particular endomembrane compartments. Studies using live cell microscopy and fluorescent proteins have illuminated the highly dynamic nature of trafficking, and electron microscopy studies have resolved the ultrastructure of many compartments. Biochemical and molecular analyses have further informed about the function of particular proteins and endomembrane compartments. In plants, there are over 40 cell types, each with highly specialised functions, and hence potential variations in cell biological processes and cell wall structure. As the primary function of secretion in plant cells is for the biosynthesis of cell wall polysaccharides and apoplastic transport complexes, it follows that utilising our knowledge of cell wall glycosyltransferases (GTs) and their polysaccharide products will inform us about secretion. Indeed, this knowledge has led to novel insights into the secretory pathway, including previously unseen post-TGN secretory compartments. Conversely, our knowledge of trafficking routes of secretion will inform us about polarised and localised deposition of cell walls and their constituent polysaccharides/glycoproteins. In this review, we look at what is known about cell wall biosynthesis and the secretory pathway and how the different approaches can be used in a complementary manner to study secretion and provide novel insights into these processes. PMID- 26993352 TI - Multifocal Renal Fungal Abscesses. AB - We report a case of multiple fungal renal abscesses in a 36-year-old woman with a history of diabetes and intravenous substance use disorder. The patient presented with fever and hematuria, and was found to be bacteremic and fungemic. She was initially managed with broad-spectrum antibiotics and antifungals. She remained febrile and imaging on treatment day 14 showed no improvement of the renal abscesses. Thus, a nephrectomy was performed, after which the patient defervesced and follow-up blood cultures were negative. There is a paucity of literature regarding management of multifocal fungal renal abscesses that fail to respond to medical management. PMID- 26993353 TI - Continent Catheterizable Vesicostomy: An Alternative Surgical Modality for Pediatric Patients With Large Bladder Capacity. AB - OBJECTIVE: To present a modified technique and early outcomes of a continent catheterizable vesicostomy in pediatric patients with either flaccid neurogenic bladder or intractable voiding dysfunction and large capacity bladder. METHODS: Six patients underwent the procedure from October 2014 to December 2015. A 4-cm Pfannenstiel incision was made, avoiding intraperitoneal dissection. After adequate mobilization, a 2-cm vertical flap at the dome of the bladder was identified and tubularized over a 12Fr catheter with 4-0 vicryl suture. The tubularized flap was then intussuscepted into the bladder with four 4-0 polydioxanone sutures, creating a continent mechanism. The catheterizable channel was then tunneled to the umbilicus, the channel ostomy matured, and the cystotomy closed in two layers. RESULTS: The median patient age was 8 (interquartile range [IQR] 12) years. All patients had urinary dysfunction requiring drainage from etiologies that included Eagle-Barrett syndrome (n = 2), Noonan syndrome (n = 1), Lennox-Gastaut syndrome (n = 1), and Spina bifida (n = 2). Median hospital length of stay was 8 (IQR 3) days. One patient had a superficial wound infection treated with antibiotics, and 1 patient required balloon dilation of the catheterizable channel at 3 months postoperatively, secondary to difficulty self-catheterizing. Five patients were successfully self-catheterizing at last follow-up. Median follow-up was 6 (IQR 5) months and there were no intra- or perioperative complications. CONCLUSION: Continent catheterizable vesicostomy is a novel technique for urinary drainage in patients with large bladder capacity that spares use of the appendix or ileum. Early results are encouraging, providing a catheterizable channel through the umbilicus without urinary leakage between catheterization. PMID- 26993354 TI - Vasitis: An Uncommon Diagnosis Mimicking Incarcerated Inguinal Hernia. AB - Vasitis or inflammation of the vas deferens is a rarely described condition. Clinically, it presents with nonspecific symptoms that can be confused with other more common conditions, especially an incarcerated inguinal hernia. The diagnosis may be suggested by ultrasound or, more precisely, by computed tomography. PMID- 26993355 TI - Assessment of Erectile Dysfunction Following Burn Injury. AB - OBJECTIVE: To determine the prevalence of erectile dysfunction (ED) following burn injury. MATERIALS AND METHODS: A cross-sectional study was conducted in 2013, recruiting 125 male patients with thermal and electrical burn injury. Using the simplified and validated Persian translation of the abridged, 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire, the patients were evaluated for the presence and severity of the ED following burn injury. RESULTS: ED was detected in 66 patients (53%). There was a significant association between the total body surface area (TBSA) and severity of ED, in which by increase in the TBSA, the severity of ED increased. There was a significant negative correlation between IIEF-5 score and age (r = -0.247, P = .005) and TBSA (r = -0.481, P < .001). The logistic regression analysis revealed that TBSA was significantly associated with ED (P < .001). CONCLUSION: Our study estimated the prevalence of ED among burn survivors to be higher than the general population. We found that TBSA is a significant risk factor of ED. PMID- 26993356 TI - Interacting quantum fragments-rooted preorganized-interacting fragments attributed relative molecular stability of the Be(II) complexes of nitrilotriacetic acid and nitrilotri-3-propionic acid. AB - A method designed to investigate, on a fundamental level, the origin of relative stability of molecular systems using Be(II) complexes with nitrilotriacetic acid (NTA) and nitrilotri-3-propionic acid (NTPA) is described. It makes use of the primary and molecular fragment energy terms as defined in the IQA/F (Interacting Quantum Atoms/Fragments) framework. An extensive classical-type investigation, focused on single descriptors (bond length, density at critical point, the size of metal ion or coordination ring, interaction energy between Be(II) and a donor atom, etc.) showed that it is not possible to explain the experimental trend. The proposed methodology is fundamentally different in that it accounts for the total energy contributions coming from all atoms of selected molecular fragments, and monitors changes in defined energy terms (e.g., fragment deformation, inter- and intra-fragment interaction) on complex formation. By decomposing combined energy terms we identified the origin of relative stability of Be(II) (NTA) and Be(II) (NTPA) complexes. We found that the sum of coordination bonds' strength, as measured by interaction energies between Be(II) ion and donor atoms, favours Be(II) (NTA) but the binding energy of Be(II) ion to the entire ligand correlates well with experimental trend. Surprisingly, the origin of Be(II) (NTPA) being more stable is due to less severe repulsive interactions with the backbone of NTPA (C and H-atoms). This general purpose protocol can be employed not only to investigate the origin of relative stability of any molecular system (e.g., metal complexes) but, in principle, can be used as a predictive tool for, e.g., explaining reaction mechanism. (c) 2016 Wiley Periodicals, Inc. PMID- 26993358 TI - A Qualitative Analysis of the Effects of Victimization History and Sexual Attitudes on Women's Hypothetical Sexual Assault Scripts. AB - This study examined qualitatively the effects of a sexual victimization history and sexual attitudes on 247 undergraduate women's written accounts of a hypothetical sexual assault. More severe victimization history was associated with script characteristics of greater alcohol use, knowing the man longer, and the context of a party. Greater endorsement of positive attitudes toward casual sex was related to script characteristics of greater alcohol use, acquiescing to the man, and not knowing the man as long. Finally, a more recent sexual assault was associated with script characteristics of having just met the man, the context of a party or date, and acquiescing to the man. PMID- 26993357 TI - Psychosocial Factors That Create Barriers to Managing Serum Phosphorus Levels in Pediatric Dialysis Patients: A Retrospective Analysis. AB - OBJECTIVE: Abnormal phosphorus homeostasis is among the medley of metabolic disturbances commonly associated with chronic kidney disease. We sought to determine the psychosocial factors that create barriers to controlling serum phosphorus levels in children on dialysis and to evaluate the perceptions of children and caregivers on the ease or difficulty of following a dietary phosphorus restriction and taking phosphorus binder medications. DESIGN: Single center cross-sectional study. SETTING: Pediatric dialysis unit at a children's hospital. SUBJECTS: Forty-eight patients on chronic hemodialysis or peritoneal dialysis (mean age: 11.03 +/- 6.88 years; 69% male). MAIN OUTCOME MEASURE: Serum phosphorus levels were recorded from electronic health records and converted to a mean phosphorus standard deviation score (SDS) for each individual. Mean phosphorus SDS values were compared to each independent categorical variable using an analysis of variance test, continuous variables were analyzed using linear regression, and logistic regression was used to determine odds ratios. RESULTS: There was a significant relationship between age and phosphorus SDS (P < .001), with patients over 13 years of age having the highest prevalence of hyperphosphatemia (88%). Patients and caregivers who identified phosphorus levels as "controlled" had lower phosphorus SDS values compared to the other subjects (P = .003). However, of the patients and caregivers who reported that serum phosphorus levels were "controlled," 46% were hyperphosphatemic. Furthermore, 73% and 87% of patients and caregivers reported that following a phosphorus restricted diet and taking phosphorus binders were "easy"; yet, 40% and 49% of these patients were hyperphosphatemic, respectively. CONCLUSION: In the present study, elevated serum phosphorus levels were most common in adolescent dialysis patients. There also appears to be a disconnect between the perceived ease of following a phosphorus-restricted diet and taking phosphorus binders and the achievement of normal serum phosphorus levels. These data further emphasize the importance of ongoing education regarding dietary and medical management requirements. PMID- 26993359 TI - Cerebral microbleeds: A clinical issue for cardiologists? PMID- 26993360 TI - Novel materials and devices in the transcatheter creation of vascular anastomosis -the future comes slowly (part 2). AB - Completion of the total cavopulmonary connection and creation of the majority of vascular anastomoses are currently usually performed surgically. The major disadvantage of the surgical approach, however, is its invasiveness, as patients undergoing cardiac surgery generally need sternotomy and cardiopulmonary bypass - often with cardiac arrest - commonly resulting in a prolonged and complicated postoperative intensive care period. Transcatheter procedures, in contrast, have a lower risk of complications, shorter intensive care and total hospital stays, and do not need a cardiopulmonary bypass or sternotomy. The second part of our review focuses on new advances in transcatheter technology, which will allow safe and effective percutaneous management of patients requiring the creation of an intervascular anastomosis and completion of the total cavopulmonary connection. It will create a therapeutic alternative able to reduce the surgical burden on this group of patients. PMID- 26993361 TI - Chronic heart failure in heart transplant recipients: Presenting features and outcome. AB - BACKGROUND: The ageing graft frequently shows coronary lesions and a restrictive physiology. AIMS: To determine the presenting features and outcome of chronic heart failure in heart transplant recipients. METHODS: In this cohort study, we compared 44 consecutive heart transplant recipients who developed chronic heart failure more than 1 year after heart transplantation with 44 control heart transplant recipients who did not develop heart failure. RESULTS: We found that patients who developed heart failure had more frequently a history of hypertension or diabetes before transplantation. During the 12 months after transplantation, significantly more patients had moderate-to-severe acute rejections (>= grade 2R) in the heart failure group than in the control group. At the time of heart failure diagnosis, systolic left ventricular function was preserved in 50% of patients and coronary angiography was normal or near normal in 36% of patients. Half of the 44 patients in the heart failure group died within 2 years of heart failure diagnosis. Ascites and end-stage renal failure requiring dialysis were significantly more frequent during follow-up in the heart failure group than in the control group (respectively, 10/44 vs 0/44 [P=0.001] and 18/44 vs 5/44 [P=0.003]). CONCLUSION: In heart transplant recipients presenting with heart failure, systolic left ventricular function is frequently preserved and coronary angiography is frequently abnormal, but may be normal or near normal. During follow-up, the main features of these patients are a high mortality rate after heart failure diagnosis, a frequent need for renal dialysis and frequent ascites. PMID- 26993362 TI - Novel materials and devices in the transcatheter management of congenital heart diseases-the future comes slowly (part 3). AB - Correction of malformations affecting the right ventricular outflow tract often results in residual abnormalities that require valve implantation at a later stage to prevent right ventricular deterioration. In the paediatric population, the pathology of congenital valve stenosis or insufficiency is often complex, options for surgical repair are limited, and valve replacement remains the only albeit unattractive-alternative. Prosthetic heart valve implantation can be performed either surgically or, nowadays, percutaneously. Current transcatheter devices allow less invasive percutaneous valve implantation in selected patients after surgical repair, but are suitable for only a small portion of paediatric patients. In addition, there is a large heterogeneous group of patients who undergo surgical constriction of the pulmonary trunk, either to reduce pulmonary blood flow or to retrain or support the left ventricle. In the third part of this review series, we focus on new biomaterials, devices and technologies that have the potential to extend transcatheter valve implantation to a broader spectrum of congenital cardiovascular lesions, with safe and durable results in children, and on transcatheter options for the creation of a partial obstruction within the pulmonary trunk (pulmonary artery banding). PMID- 26993363 TI - Doctors are urged to limit opioid prescribing. PMID- 26993364 TI - Functional phosphorylation sites in cardiac myofilament proteins are evolutionarily conserved in skeletal myofilament proteins. AB - Protein phosphorylation plays an important role in regulating cardiac contractile function, but phosphorylation is not thought to play a regulatory role in skeletal muscle. To examine how myofilament phosphorylation arose in the human heart, we analyzed the amino acid sequences of 25 cardiac phosphorylation sites in animals ranging from fruit flies to humans. These analyses indicated that of the 25 human phosphorylation sites examined, 11 have been conserved across vertebrates and four have been sporadically present in vertebrates. Furthermore, all 11 of the cardiac sites found across vertebrates were present in skeletal muscle isoforms, along with three sites that were sporadically present. Based on the conservation of amino acid sequences between cardiac and skeletal contractile proteins, we tested for phosphorylation in mammalian skeletal muscle using several biochemical techniques and found evidence that multiple myofilament proteins were phosphorylated. Several of these phosphorylation sites were validated using mass spectrometry, including one site that is present in slow- and fast-twitch troponin I (TnI), but was lost in cardiac TnI. Thus, several myofilament phosphorylation sites present in the human heart likely arose in invertebrate muscle, have been evolutionarily conserved in skeletal muscle, and potentially have functional effects in both skeletal and cardiac muscle. PMID- 26993365 TI - FABP4 is a leading candidate gene associated with residual feed intake in growing Holstein calves. AB - Ecological and economic concerns drive the need to improve feed utilization by domestic animals. Residual feed intake (RFI) is one of the most acceptable measures for feed efficiency (FE). However, phenotyping RFI-related traits is complex and expensive and requires special equipment. Advances in marker technology allow the development of various DNA-based selection tools. To assimilate these technologies for the benefit of RFI-based selection, reliable phenotypic measures are prerequisite. In the current study, we identified single nucleotide polymorphisms (SNPs) associated with RFI phenotypic consistency across different ages and diets (named RFI 1-3), using DNA samples of high or low RFI ranked Holstein calves. Using targeted sequencing of chromosomal regions associated with FE- and RFI-related traits, we identified 48 top SNPs significantly associated with at least one of three defined RFIs. Eleven of these SNPs were harbored by the fatty acid binding protein 4 (FABP4). While 10 significant SNPs found in FABP4 were common for RFI 1 and RFI 3, one SNP (FABP4_5; A90% of cases. The presence of a radiographic infiltrate in the sampling area predicted BAL culture positivity with a positive predictive value of only 61%. CONCLUSIONS: In patients with clinically suspected VAP (especially those without purulent secretions or without radiographically documented bilateral infiltrates), quantitative culture of a single BAL sample may provide an incomplete assessment of lung microbiology, without having a relevant impact on the appropriateness of antimicrobial treatment. These findings suggest that single sampling of respiratory secretions, regardless radiographic opacity, seems to be a reliable diagnostic method in the management of VAP. PMID- 26993371 TI - The impact of early detection and intervention of breast cancer-related lymphedema: a systematic review. AB - Breast cancer-related lymphedema (BCRL) has become an increasingly important clinical issue as noted by the recent update of the 2015 NCCN breast cancer guidelines which recommends to "educate, monitor, and refer for lymphedema management." The purpose of this review was to examine the literature regarding early detection and management of BCRL in order to (1) better characterize the benefit of proactive surveillance and intervention, (2) clarify the optimal monitoring techniques, and (3) help better define patient groups most likely to benefit from surveillance programs. A Medline search was conducted for the years 1992-2015 to identify articles addressing early detection and management of BCRL. After an initial search, 127 articles were identified, with 13 of these studies focused on early intervention (three randomized (level of evidence 1), four prospective (level of evidence 2-3), six retrospective trials (level of evidence 4)). Data from two, small (n = 185 cases), randomized trials with limited follow up demonstrated a benefit to early intervention (physiotherapy, manual lymphatic drainage) with regard to reducing the rate of chronic BCRL (>50% reduction) with two additional studies underway (n = 1280). These findings were confirmed by larger prospective and retrospective series. Several studies were identified that demonstrate that newer diagnostic modalities (bioimpedance spectroscopy, perometry) have increased sensitivity allowing for the earlier detection of BCRL. Current data support the development of surveillance programs geared toward the early detection and management of BCRL in part due to newer, more sensitive diagnostic modalities. PMID- 26993372 TI - Ibudilast attenuates subjective effects of methamphetamine in a placebo controlled inpatient study. AB - BACKGROUND: Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans. METHODS: Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS). RESULTS: As demonstrated by statistically-significant ibudilast * MA condition interactions (p<.05), ibudilast reduced several MA related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, 0.21]), compared to placebo. CONCLUSIONS: Ibudilast appeared to reduce reward related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy. PMID- 26993373 TI - Non-fatal overdose as a risk factor for subsequent fatal overdose among people who inject drugs. AB - OBJECTIVES: To examine the relationship between non-fatal overdose and risk of subsequent fatal overdose. METHODS: We assessed risk factors for overdose death among two prospective cohorts of persons who inject drugs (PWID) in Vancouver, Canada. Extended Cox regression was used to examine if reports of non-fatal overdose were associated with the time to fatal overdose while adjusting for other behavioral, social and structural confounders. RESULTS: Between May, 1996 and December, 2011, 2317 individuals were followed for a median of 60.8 months. In total, 134 fatal overdose deaths were identified for an incidence density of 8.94 (95% confidence interval [CI]: 7.55-10.59) deaths per 1000 person-years. During the study period there were 1795 reports of non-fatal overdose. In a multivariate model, recent non-fatal overdose was independently associated with the time to overdose mortality (adjusted hazard ratio [AHR]=1.95; 95% CI: 1.17 3.27). As well, there was a dose response effect of increasing cumulative reports of non-fatal overdose on subsequent fatal overdose. CONCLUSION: Reports of recent non-fatal overdose were independently associated with subsequent overdose mortality in a dose-response relationship. These findings suggest that individuals reporting recent non-fatal overdose should be engaged with intensive overdose prevention interventions. PMID- 26993374 TI - A randomised controlled trial comparing meat-based with human cadaveric models for teaching ultrasound-guided regional anaesthesia. AB - The aim of this prospective, blinded, randomised controlled study was to compare novices' acquisition of the technical skills of ultrasound-guided regional anaesthesia using either a meat phantom model or fresh-frozen human cadavers. The primary outcome was the time taken to successfully perform an ultrasound-guided sciatic nerve block on a cadaver; secondary outcomes were the cumulative score of errors, and best image quality of the sciatic nerve achieved. After training, the median (IQR [range]) time taken to perform the block was 311(164-390 [68-600]) s in the meat model trained group and 210 (174-354 [85-600]) s in the fresh-frozen cadaver trained group (p = 0.24). Participants made a median (IQR [range]) of 18 (14-33 [8-55]) and 15 (12-22 [8-44]) errors in the two groups respectively (p = 0.39). The image quality score was also not different, with a median (IQR [range]) of 62.5 (59.4-65.6 [25.0-100.0])% vs 62.5 (62.5-75.0 [25.0-87.5])% respectively (p = 0.58). The training and deliberate feedback improved all participants' block performance, the median (IQR [range]) times being 310 (206 532 [110-600]) s before and 240 (174-354 [85-600]) s after training (p = 0.02). We conclude that novices taught ultrasound scanning and needle guidance skills using an inexpensive and easily constructed meat model perform similarly to those trained on a cadaveric model. PMID- 26993375 TI - The perioperative outcomes of eversion carotid endarterectomy in diabetic patients aged 80 years or older. AB - BACKGROUND: Uncertainty exists about the influence of advanced age and diabetes mellitus on the clinical effect of carotid endarterectomy (CEA). This study analyzed the perioperative (30-day) outcomes of CEA in diabetic patients aged >=80 years. METHODS: Data of 1872 consecutive patients who underwent 2125 primary eversion CEAs from 1990 to 2014 at our institution were prospectively stored in a vascular surgery registry. Risk factors, medication, and indication for surgery were recorded. The 354 patients (387 CEAs) aged >=80 years formed the study base; of whom, 207 (219 CEAs) were diabetic and 147 (168 CEAs) were not. A neurologist assessed all patients preoperatively, on waking from the anesthesia, and before discharge from the hospital. All procedures were eversion CEA performed by the same surgeon under general anesthesia with routine electroencephalographic monitoring for selective shunting. RESULTS: Diabetic patients were more likely to have arterial hypertension (P = .033), cardiac disease (P = .038), peripheral aneurysmal/atherosclerotic disease (P = .046), and contralateral carotid occlusion (P = .042) than their nondiabetic counterparts. Overall, there were no deaths, two (0.51%) perioperative strokes (both in diabetic patients), and 13 nonfatal cardiac complications (3.3%), of which 10 occurred in diabetic patients, but the difference failed to reach statistical significance. CONCLUSIONS: Findings from this study show that CEA is safe and effective for stroke prevention in diabetic patients aged >=80 years, with a negligible incidence of perioperative adverse events and no deaths. PMID- 26993376 TI - The perioperative effect of concomitant procedures during open infrarenal abdominal aortic aneurysm repair. AB - BACKGROUND: Open repair of abdominal aortic aneurysms (AAAs) is occasionally performed in conjunction with additional procedures; however, how these concomitant procedures affect outcome is unclear. This study determined the frequency of additional procedures during elective open AAA repair and the effect on perioperative outcomes. METHODS: All elective infrarenal open AAA repairs between January 2003 and November 2014 in the Vascular Study Group of New England (VSGNE) were identified. Patients were grouped by concomitant procedures, which included no concomitant procedure, renal artery bypass, lower extremity bypass, other abdominal procedure, or thromboembolectomy. Analyses were performed using multivariable logistic regression. RESULTS: Of 1314 patients who underwent elective AAA repair, 153 (11.6%) had a concomitant procedure, including renal bypass in 27 (2.1%), lower extremity bypass in 28 (2.1%), other abdominal procedures in 64 (4.9%), and thromboembolectomy in 48 (3.7%). Independent risk factors for 30-day mortality were renal bypass (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.9-27.7), other abdominal procedures (OR, 4.8; 95% CI, 1.6-14.1), and thromboembolectomy (OR, 8.8; 95% CI, 3.1-24.9). Deterioration of renal function was predicted by renal bypass (OR, 5.1; 95% CI, 2.1-12.4) and thromboembolectomy (OR, 3.7; 95% CI, 1.8-7.6). Lower extremity bypass and thromboembolectomy were predictive of postoperative leg ischemia (OR, 8.9; 95% CI, 2.7-29.0; OR, 11.2; 95% CI, 4.4-28.8, respectively), and thromboembolectomy was also predictive of postoperative bowel ischemia (OR, 4.4; 95% CI, 1.6-12.0). CONCLUSIONS: Performing additional procedures during infrarenal open AAA repair is associated with increased morbidity and mortality in the postoperative period. Careful deliberation of the operative risks and the necessity of the additional interventions are therefore advised during operative planning. This study also highlights the importance of avoiding perioperative thromboembolic events. PMID- 26993377 TI - Racial disparities after vascular trauma are age-dependent. AB - OBJECTIVE: Different racial disparities exist between white and black all-cause trauma patients depending on their age group; however, the effects of race and age on outcomes after vascular trauma are unknown. We assessed whether the previously described age-dependent racial disparities after all-cause trauma persist in the vascular trauma population. METHODS: Vascular trauma patients were identified from the Nationwide Inpatient Sample (January 2005 to December 2012) using International Classification of Diseases-Ninth Edition codes. Univariable and multivariable analyses were used to compare in-hospital mortality and amputation for blacks vs whites for younger (16-64 years) and older (>=65 years) age groups. RESULTS: Black patients (n = 937) were younger, more frequently male, without insurance, and suffered from more penetrating and nonaccidental injuries than white patients (n = 1486; P < .001). On univariable analysis, blacks had a significantly higher risk of death (odds ratio, [OR], 1.78; 95% confidence interval [CI], 1.16-2.74) and a significantly lower risk of amputation (OR, 0.54; 95% CI, 0.38-0.77), but these differences were not sustained after adjusting for baseline differences between groups. When stratified by age, there were significant racial disparities in mortality and amputation on univariable analysis. After risk adjustment, these differences persisted in the older group (mortality: OR, 5.95; 95% CI, 1.42-25.0; amputation: OR, 4.21; 95% CI, 1.28-13.6; P < .001) but not the younger group (mortality: OR, 1.31; 95% CI, 0.71-2.42; amputation: OR, 0.92; 95% CI, 0.58-1.46; P = not significant). Differences in survival and amputation after vascular trauma appear to be related to a higher prevalence of nonaccidental penetrating injuries in the younger black population. Race was the single greatest predictor of poor outcomes in the older population (P <= .008). CONCLUSIONS: Older black patients are nearly five-times more likely to experience death or amputation after vascular trauma than their white counterparts. Contrary to reports suggesting that younger white patients have better outcomes after all-cause trauma than younger black patients, racial disparities among patients with traumatic vascular injuries appear to be confined to the older age group after risk adjustment. PMID- 26993379 TI - TRAF2 multitasking in TNF receptor-induced signaling to NF-kappaB, MAP kinases and cell death. AB - Tumor Necrosis Factor (TNF) is a potent inflammatory cytokine that exerts its functions through the activation of two distinct receptors, TNFR1 and TNFR2. Both receptors can activate canonical NF-kappaB and JNK MAP kinase signaling, while TNFR2 can also activate non-canonical NF-kappaB signaling, leading to numerous changes in gene expression that drive inflammation, cell proliferation and cell survival. On the other hand, TNFR1 also activates signaling pathways leading to cell death by either apoptosis or necroptosis, depending on the cellular context. A key player in TNFR1- and TNFR2-induced signaling is the RING finger protein TRAF2, which is recruited to both receptors upon their stimulation. TRAF2 exerts multiple receptor-specific functions but also mediates cross-talk between TNFR1 and TNFR2, dictating the outcome of TNF stimulation. In this review, we provide an overview of the positive and negative regulatory role of TRAF2 in different TNFR1 and TNFR2 signaling pathways. We discuss the underlying molecular mechanism of action, distinguishing between TRAF2 scaffold and E3 ubiquitin ligase functions, and the regulation of TRAF2 by specific post-translational modifications. Finally, we elaborate on some possible strategies to modulate TRAF2 function in the context of therapeutic targeting in autoimmunity and cancer. PMID- 26993378 TI - HDAC 3-selective inhibitor RGFP966 demonstrates anti-inflammatory properties in RAW 264.7 macrophages and mouse precision-cut lung slices by attenuating NF kappaB p65 transcriptional activity. AB - The increasing number of patients suffering from chronic obstructive pulmonary disease (COPD) represents a major and increasing health problem. Therefore, novel therapeutic approaches are needed. Class I HDACs 1, 2 and 3 play key roles in the regulation of inflammatory gene expression with a particular pro-inflammatory role for HDAC 3. HDAC 3 has been reported to be an important player in inflammation by deacetylating NF-kappaB p65, which has been implicated in the pathology of COPD. Here, we applied the pharmacological HDAC 3-selective inhibitor RGFP966, which attenuated pro-inflammatory gene expression in models for inflammatory lung diseases. Consistent with this, a robust decrease of the transcriptional activity of NF-kappaB p65 was observed. HDAC 3 inhibition affected neither the acetylation status of NF-kappaB p65 nor histone H3 or histone H4. This indicates that HDAC 3 inhibition does not inhibit NF-kappaB p65 transcriptional activity by affecting its deacetylation but rather by inhibiting enzymatic activity of HDAC 3. Taken together, our findings indicate that pharmacological HDAC 3-selective inhibition by inhibitors such as RGFP966 may provide a novel and effective approach toward development of therapeutics for inflammatory lung diseases. PMID- 26993380 TI - Novel multiple assessment of hepatocellular drug disposition in a single packaged procedure. AB - Better prediction of drug disposition prior to the clinical trial is critical for the efficient development of new drugs. The purpose of this study is to develop a novel multiple assessment methodology of hepatocellular drug disposition from drug uptake to efflux including biliary and basolateral excretion, in a single packaged procedure. We started a sandwich culture using rat primary hepatocytes. After five days culture, the hepatocytes were incubated with a dosing solution including CDF or Rhodamine 123. Three distinct sequences were then performed in parallel: disrupting and maintaining the tight junctions comprising a bile canalicular network at 37 degrees C, and maintaining the network at 4 degrees C. Supernatant fractions were collected from each sequence, and followed by the cell lysate collection. The disposition rates of basolateral efflux by diffusion, by transporter-mediation, biliary excretion, and residual cellular fraction of CDF and Rhodamine 123 were 38.2% and 11.0%, 26.6% and 12.1%, 18.6% and 4.9%, and, 16.7% and 72.0%, respectively. CDF was likely to excrete extracellularly whereas Rhodamine 123 tended to remain intracellularly. CDF showed a relatively higher biliary excretion rate than Rhodamine 123. This novel protocol may contribute to improve the predictability of pharmacokinetics eventually in human, and streamline new drug development. CHEMICAL COMPOUNDS: 5(6)-Carboxy-2',7' dichlorofluoroscein (PubChem CID: 132525); Rhodamine 123 (PubChem CID: 65217). PMID- 26993381 TI - Classification of anatomic involvement of the iliocaval venous outflow tract and its relationship to outcomes after iliocaval venous stenting. AB - OBJECTIVE: Iliocaval venous obstruction (ICVO) includes a wide spectrum of iliac vein and vena cava obstructive patterns but anatomic classification is lacking, making comparisons of treatment modalities difficult. The purpose of this study was to propose an anatomic classification for ICVO based on patterns of venous obstruction and to correlate severity to clinically relevant outcomes. METHODS: A multi-institutional retrospective evaluation of patients with ICVO who underwent venous stenting procedures was performed to identify anatomic patterns of iliocaval obstruction. The sites of venous disease were categorized on the basis of computed tomography or magnetic resonance venography supplemented by contrast venography or intravascular ultrasound. Proposed anatomic classification was defined as follows: type I, stenosis of a single venous segment; type II, stenosis of multiple venous segments; type III, occlusion of a single venous segment; and type IV, occlusion of multiple venous segments. Anatomic segments included in the classification scheme were defined as inferior vena cava, common iliac vein, external iliac vein, and common femoral vein. All patients underwent attempted stenting to re-establish normal iliocaval outflow. Outcomes, including initial procedural success and rethrombosis rates within 6 months, were determined for each type of ICVO. RESULTS: A consecutive 120 patients with ICVO underwent venography and attempted intervention. The type of ICVO was well distributed across all categories, with type I involvement identified in 42.5% of cases, type II in 19.2%, type III in 13.3%, and type IV in 25%. Procedural success was achieved significantly more often in types I and II ICVO (P = .02). Stent reocclusion was more frequent in type IV ICVO (26.7%) than in type I (7.8%) or type II ICVO (4.3%) (P = .009). CONCLUSIONS: On the basis of a proposed anatomic classification, the diversity of ICVO may be stratified according to the severity of venous involvement. The anatomic classification was found to correlate to the technical success and short-term patency of venous intervention. Prospective evaluation is required to further validate the utility of this new anatomic classification system. PMID- 26993382 TI - Anatomic and functional outcomes of pharmacomechanical and catheter-directed thrombolysis of iliofemoral deep venous thrombosis. AB - OBJECTIVE: Pharmacomechanical thrombolysis (PMT) and catheter-directed thrombolysis (CDT) are commonly used for the treatment of iliofemoral deep venous thrombosis (DVT). The purpose of this study was to examine the short- and long term venous patency and venous valvular function as well as clinical outcomes of patients treated for iliofemoral DVT by PMT and CDT. METHODS: A retrospective review of all patients with symptomatic DVT treated between 2006 and 2011 with PMT or CDT was performed. All patients were treated by local tissue plasminogen activator delivered with PMT or CDT. Patients were divided into two groups on the basis of initial treatment modality: patients treated by PMT alone (group 1), and those who underwent PMT and CDT or CDT alone (group 2). Group comorbidities, initial presenting symptoms, and Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification scores were compared. Postprocedural duplex ultrasound was used to assess valve function and treated vein patency rates. At all visits, Villalta and CEAP scores were recorded and compared. Group demographic and procedural results were analyzed by Fisher exact test for dichotomous variables and Kruskal-Wallis equality-of-populations rank test for the ordinal and continuous data. Kaplan-Meier survival estimates were used to assess preserved valve function as well as primary and secondary patency rates. RESULTS: There were 79 patients with 102 limbs treated for extensive iliofemoral DVT (median age, 51.5 years; range, 16.6-83.8 years). There were 18 patients in group 1 and 61 patients in group 2 (PMT + CDT [n = 54] or CDT alone [n = 7]). There were no differences in demographics or comorbidities between groups aside from malignant disease, which was more common in group 1 (35.3% vs 11.5%; P = .03). A total of 102 limbs were analyzed, 24 in group 1 and 78 in group 2. Patients in group 1 had a shorter symptom duration compared with group 2 (7 days vs 16 days; P = .011). The median number of procedures in group 1 was lower than in group 2 (P < .001). At last clinical follow-up, there was no significant difference between the Villalta and CEAP scores or the rate of clinical improvement in symptoms between groups. By Kaplan-Meier analysis, there was no difference in primary patency, secondary patency, and treated valve function at 48 months. CONCLUSIONS: This study suggests that PMT as a stand-alone therapy is as effective as CDT with or without PMT in preserving valve function and preventing postthrombotic syndrome. Long-term physiologic and functional outcomes are comparable between the modalities, with preserved venous valve function in the majority of patients. PMID- 26993383 TI - The incidence of contralateral iliac venous thrombosis after stenting across the iliocaval confluence in patients with acute or chronic venous outflow obstruction. AB - OBJECTIVE: Percutaneous transluminal angioplasty with stenting of the iliac veins is the method of choice to treat patients with symptomatic lower extremity venous outflow obstruction. The optimal method of performing this technique remains to be solved, however. One question in particular is that when braided stainless steel stents (Wallstents; Boston Scientific, Natick, Mass) are used, should these venous stents extend into the vena cava or should they stop short of this for fear of causing thrombosis of the patient's normal contralateral iliofemoral vein? It has been our practice to extend our venous stents significantly into the vena cava to coapt with the inferior vena cava (IVC) wall in the majority of patients with disease of the common iliac vein at the iliocaval junction. The aim of this study was to assess whether this placement led to thrombosis of a normal contralateral common iliac vein. METHODS: We retrospectively reviewed prospectively collected data from 2008 to 2012 in patients with symptomatic acute or chronic iliocaval venous obstruction who underwent percutaneous angioplasty and stenting at our institution. Data were collected by use of the American Venous Forum venous stent database variables. Stent patency rates and the incidence of contralateral iliac vein thrombosis were analyzed. RESULTS: In 65 patients (median age, 48 years; range, 15-80 years), 200 iliocaval stents were placed. Of these patients, 41 received ipsilateral stents that extended into the IVC and completely across the contralateral common iliac vein orifice; 39 (95%) of these had venous outflow obstruction as a result of thrombotic disease. In 22 patients (54%), post-thrombotic disease involved the IVC. All patients had stents that extended into the IVC, crossing the normal contralateral iliac vein orifice completely. Most patients (97.5%) were maintained by full anticoagulation with warfarin or low-molecular-weight heparin. Four patients (9.7%) suffered new thrombosis of the nonstented contralateral iliofemoral vein; two patients had initial involvement of the IVC, and three were totally noncompliant with their postoperative anticoagulation. Thus, 2.4% of compliant patients had new contralateral thrombosis after stenting across a normal contralateral common iliac vein and into the vena caval wall. In this select patient population, univariate analysis of patient compliance with the postoperative anticoagulation strategy showed a strong correlation with postoperative contralateral iliofemoral venous thrombosis (P = .0004). CONCLUSIONS: From these data, it appears that stenting across the iliocaval confluence can be done safely in the majority of patients maintained with therapeutic anticoagulation. In post-thrombotic patients, however, stenting across the iliocaval confluence can result in a small number of new contralateral thromboses, more often if the patients are noncompliant with anticoagulation after stenting. Current stent technology limits the ability of practitioners to treat common femoral venous obstruction precisely. Future stent development is likely to eliminate the need to cross the iliocaval confluence and risk contralateral venous thromboses. PMID- 26993384 TI - Anomalous features of iliac vein stenosis that affect diagnosis and treatment. AB - BACKGROUND: Endovenous management of venous lesions is largely derived from arterial experience. However, venous lesions, particularly iliac vein stenoses, differ from their arterial counterparts in some crucial respects. Awareness of these differences is necessary for proper diagnosis and treatment. This report expands on three such anomalous features that we have noted previously in anecdotal form: (1) a unique form of a long and diffuse stenosis (Rokitansky stenosis) that may escape diagnosis with conventional techniques; (2) the invariable failure of plain old balloon angioplasty (POBA) to relieve iliac vein stenosis (both focal and diffuse); and (3) the stent compression by venous strictures, whether focal or diffuse, extrinsic to the stent. Although these features are somewhat interrelated from the concentric fibrous structure of iliac vein stenosis, they represent different phases in the overall management of iliac vein lesions. METHODS: The analyses are derived from electronic medical records of 2534 iliac vein stent procedures performed from 1996 to 2013. Smaller subsets were used to record more detailed intravascular ultrasound planimetry data than were available in the generic database. RESULTS: The incidence of Rokitansky stenosis without focal lesions was 1.5%. After POBA, stenotic area increased from a median of 60 mm(2) to 62 mm(2), a miniscule improvement. Lumen area increased to a nearly "normal" 172 mm(2) after stent placement. In 103 limbs with residual or recurrent symptoms, in-stent restenosis (ISR) was present in all limbs; additional stent compression was evident in 25% of the limbs, adding to the overall severity of the stenosis. ISR responded well to high-pressure balloon dilation, with total clearance in 62% of treated limbs and substantial improvement in others. In contrast, stent compression was resistant, remaining unchanged in 68% after balloon dilation. CONCLUSIONS: Rokitansky stenosis is easily missed with conventional diagnostic techniques and may not be recognizable even with intravascular ultrasound, unless routine planimetry is used. POBA as a primary treatment invariably fails to correct focal or diffuse iliac vein stenosis, and stenting is always required. Stent compression is a unique feature of iliac vein stenosis, whether it is focal or diffuse. It often occurs in association with ISR, when overall stenosis can be underestimated if stent compression is not taken into account. Stent compression responds poorly to balloon dilation, whereas the associated ISR shows complete clearance in the majority of treated limbs. PMID- 26993385 TI - Endovascular intervention for pelvic congestion syndrome is justified for chronic pelvic pain relief and patient satisfaction. AB - OBJECTIVE: Pelvic congestion syndrome (PCS) is difficult to diagnose, poorly understood, and often confused with other causes of chronic pelvic pain. Thus, gonadal vein reflux, its relation to lower extremity venous insufficiency (LEVI), and treatment remains controversial to physicians and payors. We present our experience with endovascular PCS treatment and hypothesize that properly selected patients can realize significant improvement. METHODS: A retrospective study of patients treated for PCS at our institution from 2008 to 2012 was performed. Diagnosis was made clinically by the presence of pelvic pain, dyspareunia, and/or perineal varicosities. Clinical parameters, procedural details, and follow-up were reviewed. A questionnaire including a visual analog scale was sent to patients. RESULTS: Diagnosis was made in 15 women (mean age, 36 years; mean parity, two). All had pelvic pain, 6 had dyspareunia, 14 had perineal varicosities, and 10 had concomitant LEVI. Fourteen had gonadal vein reflux (mean diameter, 7.4 mm) and pelvic varicosities at angiography and had coiling (n = 12) and/or Amplatzer plug (St. Jude Medical, Inc, St. Paul, Minn) (n = 4). One patient had stenting of a stenotic left common iliac vein. All patients with concomitant LEVI had successful appropriate treatment. Eight patients completed the questionnaire at a mean follow-up of 4 years. The mean pelvic pain score went from 9.375 to 1.875 post-procedure (P < .0001; Student t-test). Mean dyspareunia score went from 8.875 to 1.5 (P < .0001). Mean perineal varicosity pain score went from 9.285 to 1.285 (P < .0001). Two patients had recurrence with a mean pelvic pain score of 4.5 at a mean 21 months. On a five-point Likert scale, all patients were satisfied (one) or extremely satisfied (seven) with treatment. CONCLUSIONS: Endovascular PCS treatment offers excellent pelvic pain relief and patient satisfaction. Women with pelvic pain, dyspareunia, or perineal varicosities with gonadal vein reflux and pelvic varicosities or iliac vein stenosis should not be denied treatment. A significant number may have concomitant LEVI and should be screened accordingly. PMID- 26993386 TI - Inferior vena cava filter placement during thrombolysis for acute iliofemoral deep venous thrombosis. AB - OBJECTIVE: The objectives of this study were to evaluate the need for inferior vena cava (IVC) filters and to identify anatomic and patient-specific risk factors associated with embolization in patients undergoing thrombolysis for acute iliofemoral deep venous thrombosis (DVT). METHODS: Consecutive patients who underwent catheter-directed thrombolysis or pharmacomechanical thrombolysis (PMT) for iliofemoral DVT from May 2007 to March 2012 were identified from a prospectively maintained database. Patients were categorized in two groups, depending on the status of IVC filtration during the lysis procedures: patients with an IVC filter protection (group A) and patients without an IVC filter protection (group B). The primary outcome was perioperative clinically significant pulmonary embolism (PE) or intraprocedural IVC filter clot capture. RESULTS: Eighty patients (mean age, 50 +/- 16 years; 39 women) with symptoms averaging 12 +/- 10 days were treated. A perioperative IVC filter was placed in 32 patients, and nine patients had an indwelling patent filter (group A, n = 41). Twenty patients received no filter, and 19 patients had an indwelling thrombosed filter (group B, n = 39). There were no clinically significant PE in either group. In group A, nine patients (22%) had documented embolic clot within the filter nest. The clot volume was deemed clinically significant in only two patients (5%). Factors related to embolization included female gender (odds ratio [OR], 5.833; 95% confidence interval [CI], 1.038-32.797; P = .032) and preoperative clinical PE (OR, 5.6; 95% CI, 1.043-30.081; P = .054). A trend for increased embolization was seen with a higher average number of DVT risk factors (1.44 vs 1; P = .065) and when PMT was used as a single treatment (OR, 4.32; 95% CI, 0.851-21.929; P = .087). CONCLUSIONS: IVC filters during thrombolysis should be used selectively in patients with preoperative clinical PE, in women and potentially in patients with multiple risk factors for DVT, or when stand-alone PMT is planned. PMID- 26993387 TI - Mechanochemical endovenous ablation for the treatment of great saphenous vein insufficiency. AB - OBJECTIVE: This study evaluated the feasibility, safety, and 1-year results of mechanochemical endovenous ablation (MOCA) of great saphenous vein (GSV) insufficiency. METHODS: A consecutive 106 patients were treated for primary GSV insufficiency with MOCA by the ClariVein device and polidocanol. The primary outcome measures were technical success, clinical success, and anatomic success after 1 year of follow-up. Secondary outcome measures were postprocedural pain, complications, general- and disease-specific quality of life, and time to return to work. Patients were evaluated with clinical examination and duplex ultrasonography at 6 weeks, 6 months, and 1 year after treatment. RESULTS: The technical success was 99%. The mean postprocedural pain during the first 14 days after treatment was 7.5 mm (interquartile range [IQR], 0.0-10.0 mm) per day on a 0- to 100-mm visual analog scale. The time to return to normal activities and work was 1.0 day (IQR, 0-1.0 day) and 1.0 day (IQR, 1.0-4.0 days), respectively. No major complications were recorded. At 1-year follow-up, the clinical success was 93%. The Venous Clinical Severity Score decreased significantly from 4.0 (IQR, 3.0-5.0) before treatment to 1.0 (IQR, 0-1.0) (P < .001) 1 year after MOCA. At 1 year, 88.2% of the treated GSVs remained occluded as measured by duplex ultrasonography. Twelve patients had a recanalization, of which eight were partial. Disease-specific quality of life and the RAND 36-Item Health Survey scores improved significantly at 1-year follow-up. CONCLUSIONS: MOCA is a safe and effective technique in the treatment of GSV insufficiency with good clinical and anatomic success at 1-year follow-up. The technique is related to low postprocedural pain scores, low complication rate, improved quality of life, and rapid resumption of normal activities and work. PMID- 26993388 TI - Role of compression stockings after endovenous laser therapy for primary varicosis. AB - OBJECTIVE: The objective of this prospective, randomized trial was to evaluate the effect of compression stockings after endovenous laser therapy (EVLT) for insufficiency of the great saphenous vein. Effect evaluation was focused on differences in postoperative pain within 6 weeks. METHODS: The study randomized 111 patients undergoing EVLT for duplex ultrasound-confirmed great saphenous vein insufficiency (C2-4EPASPR) to receive either 2 weeks of elastic stockings (class II, thigh length) or no elastic stockings after an initial 24-hour period of wearing bandages. Patients registered pain scores (primary outcome) and use of analgesics in a diary on a visual analog scale. At 2 days, 14 days, and 6 weeks after the procedure, leg circumferences, Aberdeen Varicose Vein Questionnaire scores, RAND 36-Item Health Survey scores, patient satisfaction (5-point scale), time before returning to work, and adverse events (secondary outcomes) were evaluated. RESULTS: In the 79 patients (15 men and 64 women; mean age, 52 years) who completed the treatment and follow-up, small but significant differences in pain scores were observed during the first week after laser surgery, with more favorable scores in the group wearing stockings. Patients not wearing stockings used more analgesics than did patients wearing stockings (P < .05). Patients wearing stockings reported a statistically significantly higher score of satisfaction at 2 days (4.44 vs 4.15) and 6 weeks (4.59 vs 4.18), although the absolute differences were small. No significant differences were found regarding time to return to work, Aberdeen Varicose Vein Questionnaire scores, RAND 36-Item Health Survey scores, leg circumference measurements, and risk of complications. CONCLUSIONS: Wearing of postoperative stockings for 2 weeks after an initial 24 hour period of wearing bandages results in a small but significant reduction of postoperative pain and use of analgesics compared with not wearing compression stockings after EVLT for great saphenous vein insufficiency. PMID- 26993389 TI - Limited venoplasty and anticoagulation affords excellent results after first rib resection and scalenectomy for subacute Paget-Schroetter syndrome. AB - OBJECTIVE: We have previously demonstrated excellent mid-term patency rates following routine venography after first rib resection and scalenectomy (FRRS) for subacute Paget-Schroetter syndrome. The goal of this study was to assess the long-term outcomes of this technique. METHODS: Retrospective analysis of a prospectively collected database was performed. Patients underwent routine venography 2 weeks post-FRRS. Warfarin was discontinued in those with patent veins. Patients with stenotic or occluded veins underwent attempted venoplasty with balloon diameters approximating the size of the anatomically normal vein. Patients with successful venoplasty or chronically occluded veins unable to be dilated were continued on warfarin up to 6 months. Follow-up duplex ultrasound dictated cessation of anticoagulation. Kaplan-Meier analysis was performed for primary, primary-assisted, and secondary patency. RESULTS: A total of 159 patients underwent FRRS and postoperative venography with a median follow-up of 13.8 months. One patient was lost to follow-up. The median time to FRRS after the initial onset of symptoms was 4.1 months. At the time of venography, there were 42 patent, 72 stenotic, and 44 occluded veins. Of the 44 occlusions, 25 underwent venoplasty, and 19 could not be crossed. In the entire group, restenosis occurred in seven patients and reocclusion in seven. At last follow-up, six patients remained occluded. Eighteen-month primary patency of venoplasty was 95.4% +/- 2.6% in the stenotic group and 75.6% +/- 8.7% in the occluded group. Eighteen month primary-assisted patency of venoplasty was 98.3% +/- 1.7% in the stenotic group and 96.0% +/- 3.9% in the occluded group. Overall secondary patency at 3 years was 100% in the patent group, 98.4% +/- 1.6% in the stenotic group, and 92.9% +/- 3.9% in the occluded group. CONCLUSIONS: Long-term venous patency rates after limited venoplasty and anticoagulation following FRRS are excellent. Furthermore, prolonged anticoagulation for occlusions that could not be crossed or in those who reocclude after venoplasty results in recanalization and delayed patency. These results argue against the need for stenting or open venous reconstruction and serve as a benchmark for the care of patients with subacute Paget-Schroetter syndrome. PMID- 26993390 TI - Hemodynamic coupling of a pair of venous valves. AB - BACKGROUND: In vivo studies have shown that valves in veins are paired in an orthogonal configuration. The aim of this study is to characterize the flow interaction of paired valves under controlled in vitro bench conditions. METHODS: A bench top in vitro experiment was set up at physiological flow conditions to simulate the flow inside a venous valve. Two bicuspid bioprosthetic valves paired in 0 degrees and 90 degrees orientations were tested in a 12-mm-diameter tube, and the two-dimensional velocity fields around the valve were measured by particle image velocimetry. The distance between the two valves was varied from 3 to 5 cm, and the corresponding velocities and vorticities were determined. RESULTS: Velocity field shows the flow exit from the orthogonal valve-pairing configurations forced the main jet stream to turn to the outer region of the tube. Flow patterns between the valves show significantly less stagnation region from the 90 degrees valve pairing over a 0 degrees valve pairing case. The variation in valves distance shows that the coupling effect of the two valves extends to a range beyond four times of the tube diameter, albeit the ability to alter the flow decreases at larger distances. CONCLUSIONS: The findings suggest that the 90 degrees valve pairing configuration regulates the flow between the valves, and the separation distance affects the hemodynamic efficiency of the two valves by reducing the total reverse flow volume. PMID- 26993391 TI - Experimental determination of the best time and duration for endovenous great saphenous vein electrocoagulation. AB - OBJECTIVE: Endovenous electrocoagulation provokes immediate selective venous wall necrosis. In this study, we aim to determine the best power and time of electrocoagulation necessary to cause intima and media but not adventitia layer damage in great saphenous vein (GSV) insufficiency treatment. METHODS: We studied 100 varicose GSV fragments submitted to endovenous electrocoagulation. The power (60, 90, or 120 W) and time (5, 10, or 15 seconds) were randomly assigned. The fragments were submitted to histopathologic examination to analyze the depth of tissue necrosis. Dose-response models for the analysis of binary data were used to identify the best association between power and the time of electrocoagulation necessary to cause intima and media but not adventitia layer necrosis. We also applied a logistic regression model to investigate the impact of body mass index and GSV diameter on the electrocoagulation effects. RESULTS: The time (odds ratio [OR], 1.26; P = .0009) was found to be a stronger predictor of the depth of vessel necrosis than the power of electrocoagulation applied (OR, 1.05; P < .0001). The power and time that were most likely to cause intima and media but not adventitia layer destruction were 60.4 W * 5 seconds, 58.8 W * 10 seconds, and 8.9 W * 15 seconds. The initial GSV diameter (median, 5.36 mm; minimum, 2.3 mm; maximum, 10 mm; OR, 0.96; P = .82) and body index mass (median, 24.7 kg/m(2); minimum, 15.6 kg/m(2); maximum, 36.2 kg/m(2); OR, 1.08; P = .26) showed a poor correlation with the depth of histologic vessel destruction. CONCLUSIONS: The time of electrocoagulation strongly predicts the depth of GSV wall necrosis more than the amount of power applied. Determination of the best time and power of electrocoagulation ratio may help optimize GSV endovenous electrocoagulation closure rates and decrease the complications index. The GSV diameter and body mass index do not influence endovenous electrocoagulation effects. PMID- 26993392 TI - Treatment of mesenteric vein thrombosis with transjugular mechanical thrombectomy and subsequent simultaneous arterial and venous thrombolysis. AB - Mesenteric vein thrombosis may induce intestinal ischemia and gangrene. In severe cases, it is necessary to restore venous outflow from the small intestine rapidly. We describe a severe case of mesenteric vein thrombosis that was resolved successfully by mechanical thrombectomy from a transjugular approach followed by selective simultaneous venous and arterial thrombolysis via the superior mesenteric vein and artery. In conclusion, the transjugular intrahepatic portosystemic approach was a feasible and safe access for mechanical thrombectomy and thrombolysis of the mesenteric vein in our patient. PMID- 26993393 TI - Recanalization and stenting of a post-thrombotic iliac vein in a patient with Behcet's disease. AB - Vascular lesions are frequent in Behcet's disease, and among them, deep venous thrombosis may occur in up to one-third of patients. Treatment is based on immunosuppressive drugs in addition to anticoagulants. We report the case of a young woman who presented with an acute iliofemoral venous thrombosis. Acute treatment with endovascular thrombectomy and catheter-directed fibrinolysis failed, probably because of the inflammatory status of the vessel wall. Recanalization with stenting of the obstructed common femoral and iliac veins 1 year later was successful under immunosuppressive therapy. This case suggests that endovascular treatment of venous thrombosis in Behcet's disease may be conducted successfully in nonactive venous lesions under immunosuppressive therapy. PMID- 26993394 TI - Interrupted inferior vena cava with azygos and hemiazygos continuation associated with scimitar vein draining to infrahepatic inferior vena cava. PMID- 26993395 TI - A giant azygos venous aneurysm caused by the resection of hemangioma. PMID- 26993396 TI - The calf muscle pump revisited. AB - BACKGROUND: Chronic venous disease (CVD) defines the spectrum of manifestations of venous disease that originate as a result of ambulatory venous hypertension. Thus far, the role of the calf muscle pump in the development and potentiation of CVD has been overlooked and understated in the clinical setting, with much greater emphasis placed on reflux and obstruction. The aim of this review is to explore the level of significance that calf muscle pump function or dysfunction bears on the development and potentiation of CVD. METHODS: EMBASE and MEDLINE databases were searched with keywords "calf" AND "muscle" AND "pump" AND "venous" AND "insufficiency" AND ("lower limb*" OR "leg*"), screened for cross-sectional and longitudinal studies relating to chronic venous insufficiency, highlighting the role of the calf muscle pump in CVD and the extent to which the calf muscle pump is impaired in these cases. This resulted in the inclusion of 10 studies. RESULTS: Compared with healthy subjects, patients with CVD have a reduced ejection fraction (15.9%; P < .001) and an increased venous filling index (4.66 mL/s; P < .001), indicating impairment in calf muscle pump ejection ability as well as poor venous competence. Calf muscle pump dysfunction is present in 55% of patients with CVD in the literature, but this did not reach significance on meta analysis. Isotonic exercise programs in patients with active and healed ulcers have been shown to increase calf muscle pump function but not venous competence. DISCUSSION: Calf muscle pump failure is a therapeutic target in the treatment of CVD. Evidence suggests that isotonic exercise treatment may be an effective method of increasing the hemodynamic performance of the calf muscle pump. CONCLUSIONS: This review emphasizes the requirement for more attention to be placed on the treatment of calf muscle pump failure in cases of CVD by use of exercise treatment programs or other methods, which may be of clinical importance in managing symptomatic disease. To establish this in routine clinical practice, these results would need to be replicated in appropriate clinical trials. It would also be logical to look at other modifiable muscle pumps, such as the thigh and foot, and to explore the potential benefit of electrical devices acting on the leg (eg, electrical muscular or neuromuscular stimulation), especially for those patients in whom exercise capacity is limited. PMID- 26993397 TI - The utility of venous thromboembolism risk assessment models in general and vascular surgery. AB - Venous thromboembolism (VTE) is a common postsurgical complication, the incidence of which can be reduced with the use of various prophylactic measures. Proper use of these measures requires an understanding of each individual patient's risk of VTE. Risk assessment models have been developed to aid clinicians in quantifying the likelihood of an individual VTE formation. In this review, we discuss several models of risk assessment for general and vascular surgery patients with a focus on both sensitivity and prospective validation by external sources. In addition, strategies to improve proper implementation of prophylactic measures are highlighted. PMID- 26993398 TI - The American Venous Forum: Leveraging our strengths. PMID- 26993400 TI - Events of interest. PMID- 26993399 TI - Clinical presentation, diagnosis, and treatment of venous aneurysms. AB - Venous aneurysms have been reported in most major veins and are often asymptomatic but can cause serious complications. Three patients with symptomatic venous aneurysms of the internal jugular vein, portal vein, and popliteal vein are presented, and their treatment and outcomes are discussed. Furthermore, presentation and management of the most frequent venous aneurysms, based on available literature, are evaluated. The literature supports conservative treatment of asymptomatic and nonthrombotic jugular, subclavian, thoracic, and visceral venous aneurysms. Surgery should be considered only for symptomatic venous aneurysms or in case of progressive expansion on follow-up. Prophylactic surgery is recommended for all patients with lower extremity deep venous aneurysms, by means of tangential aneurysmectomy with lateral venorrhaphy, because of the increased risk of pulmonary embolization. Postoperative anticoagulation is recommended for a period of at least 3 months after operative treatment. PMID- 26993402 TI - Information for readers. PMID- 26993403 TI - Cytokines in cancer drug resistance: Cues to new therapeutic strategies. AB - The development of oncoprotein-targeted anticancer drugs is an invaluable weapon in the war against cancer. However, cancers do not give up without a fight. They may develop multiple mechanisms of drug resistance, including apoptosis inhibition, drug expulsion, and increased proliferation that reduce the effectiveness of the drug. The collective work of researchers has highlighted the role of cytokines in the mechanisms of cancer drug resistance, as well as in cancer cell progression. Furthermore, recent studies have described how specific cytokines secreted by cancer stromal cells confer resistance to chemotherapeutic treatments. In order to gain a better understanding of mechanism of cancer drug resistance and a prediction of treatment outcome, it is imperative that correlations are established between global cytokine profiles and cancer drug resistance. Here we discuss the recent discoveries in this field of research and discuss their implications for the future development of effective anti-cancer medicines. PMID- 26993404 TI - Noise in the ICU patient room - Staff knowledge and clinical improvements. AB - INTRODUCTION: The acoustic environment in the intensive care unit patient room, with high sound levels and unpredictable sounds, is known to be poor and stressful. Therefore, the present study had two aims: to investigate staff knowledge concerning noise in the intensive care unit and: to identify staff suggestions for improving the sound environment in the intensive care unit patient room. METHOD: A web-based knowledge questionnaire including 10 questions was distributed to 1047 staff members at nine intensive care unit. Moreover, 20 physicians, nurses and enrolled nurses were interviewed and asked to give suggestions for improvement. RESULTS: None of the respondents answered the whole questionnaire correctly; mean value was four correct answers. In the interview part, three categories emerged: improving staff's own care actions and behaviour; improving strategies requiring staff interaction; and improving physical space and technical design. CONCLUSION: The results from the questionnaire showed that the staff had low theoretical knowledge concerning sound and noise in the intensive care unit. However, the staff suggested many improvement measures, but also described difficulties and barriers. The results from this study can be used in the design of future interventions to reduce noise in the intensive care unit as well as in other settings. PMID- 26993405 TI - [Evaluation of sciatic nerve damage following intraneural injection of bupivacaine, levobupivacaine and lidocaine in rats]. AB - OBJECTIVE: The local anesthetics may cause neurotoxicity. We aimed to compare the neurotoxic potential of different local anesthetics, local anesthetic induced nerve damage and pathological changes of a peripheral nerve. METHODS: Sixty Wistar rats weighing 200-350g were studied. Rats were assigned into 3 groups and 26-gauge needle was inserted under magnification into the left sciatic nerve and 0.2mL of 0.5% bupivacaine, 5% levobupivacaine, and 2% lidocaine were injected intraneurally. An individual who was blind to the specifics of the injection monitored the neurologic function on postoperative 1st day, and daily thereafter. Neurologic examination included assessment for the presence and severity of nociception and grasping reflexes. At the 7th day sciatic nerve specimen was taken for evaluation of histopathologic changes. RESULTS: There was no statistical difference detected among groups regarding grasping reflex and histopathologic evaluation. Two cases in bupivacaine group, 1 case in levobupivacaine group and 2 cases in lidocaine group had slight grasping, while 1 case in lidocaine group had no grasping reflex on the seventh day. Severe axonal degeneration was observed in all groups, respectively in bupivacaine group 4 (20%), levobupivacaine group 3 (15%), and lidocaine group 6 (30%). CONCLUSION: In all groups, histopathological damage frequency and severity were more than the motor deficiency. PMID- 26993406 TI - [Comparative study between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on endotracheal tube cuff as regards postoperative sore throat]. AB - Postoperative sore throat is a common complication after endotracheal intubation. After tracheal intubation, the incidence of sore throat varies from 14.4% to 50%. The aim of the study was to compare between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on the endotracheal tube cuff as regards postoperative sore throat. The present study was carried out on 124 patients admitted to Alexandria university hospitals for lumbar fixation surgery requiring general anesthesia. Patients were randomly allocated into 4 groups. Benzydamine hydrochloride gel, 5% lidocaine hydrochloride gel, 10% lidocaine hydrochloride spray, or normal saline were applied on endotracheal tube cuffs before endotracheal intubation. The patients were examined for sore throat (none, mild, moderate, or severe) at 0, 1, 6, 12, and 24h after extubation. The results were collected, analyzed and presented in table and figure. The highest incidence of postoperative sore throat occurred at 6h after extubation in all groups. There was a significantly lower incidence of postoperative sore throat in the benzydamine group than 5% lidocaine gel, 10% lidocaine spray, and normal saline groups. The benzydamine group had significantly decreased severity of postoperative sore throat compared with the 10% lidocaine, 5% lidocaine, and normal saline groups at observation time point. Compared with the 5% lidocaine the 10% lidocaine group had significantly increased incidence and severity of postoperative sore throat after extubation. Compared with normal saline the 10% lidocaine group had increased incidence of postoperative sore throat. There were no significant differences among groups in local or systemic side effects. So in conclusion, benzydamine hydrochloride gel on the endotracheal tube cuff is a simple and effective method to reduce the incidence and severity of postoperative sore throat. Application of 10% lidocaine spray should be avoided because of worsening of postoperative sore throat where incidence increased but not the severity in relation to 5% lidocaine gel. Applying 5% lidocaine on the endotracheal tube cuff does not prevent postoperative sore throat but its application is better than lidocaine 10% spray or saline. PMID- 26993407 TI - [Analysis of cricoid pressure application: anaesthetic trainee doctors vs. nursing anaesthetic assistants]. AB - BACKGROUND AND OBJECTIVE: To evaluate the ability of anaesthetic trainee doctors compared to nursing anaesthetic assistants in identifying the cricoid cartilage, applying the appropriate cricoid pressure and producing an adequate laryngeal inlet view. METHODS: Eighty-five participants, 42 anaesthetic trainee doctors and 43 nursing anaesthetic assistants, were asked to complete a set of questionnaires which included the correct amount of force to be applied to the cricoid cartilage. They were then asked to identify the cricoid cartilage and apply the cricoid pressure on an upper airway manikin placed on a weighing scale, and the pressure was recorded. Subsequently they applied cricoid pressure on actual anaesthetized patients following rapid sequence induction. Details regarding the cricoid pressure application and the Cormack-Lehane classification of the laryngeal view were recorded. RESULTS: The anaesthetic trainee doctors were significantly better than the nursing anaesthetic assistants in identifying the cricoid cartilage (95.2% vs. 55.8%, p=0.001). However, both groups were equally poor in the knowledge about the amount of cricoid pressure force required (11.9% vs. 9.3% respectively) and in the correct application of cricoid pressure (16.7% vs. 20.9% respectively). The three-finger technique was performed by 85.7% of the anaesthetic trainee doctors and 65.1% of the nursing anaesthetic assistants (p=0.03). There were no significant differences in the Cormack-Lehane view between both groups. CONCLUSION: The anaesthetic trainee doctors were better than the nursing anaesthetic assistants in cricoid cartilage identification but both groups were equally poor in their knowledge and application of cricoid pressure. PMID- 26993408 TI - [A comparative study between propofol and etomidate in patients under general anesthesia]. AB - BACKGROUND AND OBJECTIVES: Induction of anesthesia is a critical part of anesthesia practice. Sudden hypotension, arrhythmias, and cardiovascular collapse are threatening complications following injection of induction agent in hemodynamically unstable patients. It is desirable to use a safe agent with fewer adverse effects for this purpose. Present prospective randomized study is designed to compare propofol and etomidate for their effect on hemodynamics and various adverse effects on patients in general anesthesia. METHODS: Hundred ASA I and II patients of age group 18-60 years scheduled for elective surgical procedure under general anesthesia were randomly divided into two groups of 50 each receiving propofol (2mg/kg) and etomidate (0.3mg/kg) as an induction agent. Vital parameters at induction, laryngoscopy and thereafter recorded for comparison. Adverse effect viz. pain on injection, apnea and myoclonus were carefully watched. RESULTS: Demographic variables were comparable in both the groups. Patients in etomidate group showed little change in mean arterial pressure (MAP) and heart rate (HR) compared to propofol (p>0.05) from baseline value. Pain on injection was more in propofol group while myoclonus activity was higher in etomidate group. CONCLUSIONS: This study concludes that etomidate is a better agent for induction than propofol in view of hemodynamic stability and less pain on injection. PMID- 26993409 TI - [A randomised crossover trial comparing the Airtraq((r)) NT, McGrath((r)) MAC and Macintosh laryngoscopes for nasotracheal intubation of simulated easy and difficult airways in a manikin]. AB - OBJECTIVE: Several devices can aid nasotracheal intubation when managing difficult airways. The McGrath MAC and Airtraq NT were compared with a Macintosh laryngoscope when studying the performance of anaesthetists with different levels of experience, in a manikin model of easy or difficult airway scenarios. METHODS: Sixty-three anaesthetists were recruited into a randomised trial in which each performed nasotracheal intubation with all laryngoscopes, in both scenarios. The main endpoint was intubation time. Additional endpoints included laryngoscopic view, intubation success, number of optimisation manoeuvres, audible dental clicks and the force applied to the upper airway. RESULTS: Intubation time was significantly shorter using the McGrath MAC in both scenarios and using the Airtraq in the difficult scenario, when compared with the Macintosh laryngoscope. Both devices gave more Cormack and Lehane grade 1 or 2 views than the Macintosh in the difficult scenario (p<0.001). The McGrath MAC had the best first-attempt success rate (98.4% vs. 96.8% and 95.8%, p<0.001 for the Airtraq NT and Macintosh laryngoscopes respectively). The number of optimisation manoeuvres, audible dental clicks and subjective assessment of the degree of force applied were significantly lower for indirect laryngoscopes versus the Macintosh laryngoscope (p<0.001). CONCLUSION: In a manikin, the Airtraq and the McGrath laryngoscopes appeared superior to the Macintosh laryngoscope when dealing with simulated airway scenarios. Both devices were associated with better views, intubation times and rates of success, especially in a simulated "difficult airway". Overall satisfaction was highest with the McGrath laryngoscope. Similar clinical studies are needed. PMID- 26993410 TI - [Combined spinal-epidural analgesia in labour: its effects on delivery outcome]. AB - BACKGROUND AND OBJECTIVES: Combined spinal-epidural (CSE) has become an increasingly popular alternative to traditional labour epidural due to its rapid onset and reliable analgesia provided. This was a prospective, convenient sampling study to determine the effects of CSE analgesia on labour outcome. METHODS: One hundred and ten healthy primigravida parturients with a singleton pregnancy of >=37 weeks gestation and in the active phase of labour were studied. They were enrolled to the CSE (n=55) or Non-CSE (n=55) group based on whether they consented to CSE analgesia. Non-CSE parturients were offered other methods of labour analgesia. The duration of the first and second stage of labour, rate of instrumental vaginal delivery and emergency cesarean section, and Apgar scores were compared. RESULTS: The mean duration of the first and second stage of labour was not significantly different between both groups. Instrumental delivery rates between the groups were not significantly different (CSE group, 11% versus Non CSE group, 16%). The slightly higher incidence of cesarean section in the CSE group (16% versus 15% in the Non-CSE group) was not statistically significant. Neonatal outcome in terms of Apgar score of less than 7 at 1 and 5min was similar in both groups. CONCLUSION: There were no significant differences in the duration of labour, rate of instrumental vaginal delivery and emergency cesarean section, and neonatal outcome in parturients who received compared to those who did not receive CSE for labour analgesia. PMID- 26993411 TI - [Post analysis simulated correlation of the El-Ganzouri airway difficulty score with difficult airway]. AB - BACKGROUND: Difficult airway (DA) occurs frequently (5-15%) in clinical practice. The El-Ganzouri Risk Index (EGRI) has a high sensitivity for predicting a difficult intubation (DI). However difficult mask ventilation (DMV) was never included in the EGRI. Since DMV was not included in the EGRI assessment, and obstructive sleep apnea (OSA) is also correlated with DMV, a study correlating the prediction of DA and OSA (identified by STOP-Bang questionnaire, SB) seemed important. METHODS: We accessed a database previously collected for a post analysis simulation of the airway difficulty predictivity of the EGRI, associated with normal and difficult airway, particularly DMV. As secondary aim, we measured the correlation between the SB prediction system and DA, compared to the EGRI. RESULTS: A total of 2747 patients were included in the study. The proportion of patients with DI was 14.7% (95% CI 13.4-16) and the proportion of patients with DMV was 3.42% (95% CI 2.7-4.1). The incidence of DMV combined with DI was (2.3%). The optimal cutoff value of EGRI was 3. EGRI registered also an higher ability to predict DMV (AUC=0.76 (95% CI 0.71-0.81)). Adding the SB variables in the logistic model, the AUC increases with the inclusion of "observed apnea" variable (0.83 vs. 0.81, p=0.03). The area under the ROC curve for the patients with DI and DMV was 0.77 (95% CI 0.72-0.83). CONCLUSIONS: This study confirms that the incidence of DA is not negligible and suggests the use of the EGRI as simple bedside predictive score to improve patient safety. PMID- 26993413 TI - [Good clinical practice guide for opioids in pain management: the three Ts - titration (trial), tweaking (tailoring), transition (tapering)]. AB - BACKGROUND AND OBJECTIVES: Achieving good clinical practice in the use of opioids as part of a comprehensive pain management regimen can face significant challenges. Despite guidelines from governmental and pain society/organization sources, there are still significant hurdles. A review of some basic tenets of opioid analgesia based on current published knowledge and experiences about this important healthcare imperative is warranted. CONTENT: Consistent with guidelines, the literature supports using the lowest total opioid dose that provides adequate pain control with the fewest adverse effects. Titration (or trial) during opioid initiation is a way of starting low and going slow (and assessing the appropriateness of a specific opioid and formulation). Recognizing that multiple factors contribute to an individual's personal experience of pain, the physical, psychological, social, cultural, spiritual, pharmacogenomic, and behavioral factors of the individual patient should be taken into account (tweaking, or tailoring). Finally, for those patients for whom transition (tapering) from opioid is desired, doing so too rapidly can have negative consequences and minimization of problems during this step can be achieved by proper tapering. CONCLUSION: We conclude that a simultaneously aggressive, yet conservative, approach is advocated in the literature in which opioid therapy is divided into three key steps (the 3 T's): titration (or trial), tweaking (or tailoring), and transition (or tapering). Establishment of the 3 T's along with the application of other appropriate good medical practice and clinical experience/judgment, including non-pharmacologic approaches, can assist healthcare providers in the effort to achieve optimal management of pain. PMID- 26993412 TI - [Effects of carbon dioxide insufflation on regional cerebral oxygenation during laparoscopic surgery in children: a prospective study]. AB - BACKGROUND AND OBJECTIVES: Laparoscopic surgery has become a popular surgical tool when compared to traditional open surgery. There are limited data on pediatric patients regarding whether pneumoperitoneum affects cerebral oxygenation although end-tidal CO2 concentration remains normal. Therefore, this study was designed to evaluate the changes of cerebral oxygen saturation using near-infrared spectroscope during laparoscopic surgery in children. METHODS: The study comprised forty children who were scheduled for laparoscopic (Group L, n=20) or open (Group O, n=20) appendectomy. Hemodynamic variables, right and left regional cerebral oxygen saturation (RrSO2 and LrSO2), fraction of inspired oxygen, end-tidal carbon dioxide pressure (PETCO2), peak inspiratory pressure (Ppeak), respiratory minute volume, inspiratory and end-tidal concentrations of sevoflurane and body temperature were recorded. All parameters were recorded after anesthesia induction and before start of surgery (T0, baseline), 15min after start of surgery (T1), 30min after start of surgery (T2), 45min after start of surgery (T3), 60min after start of surgery (T4) and end of the surgery (T5). RESULTS: There were progressive decreases in both RrSO2 and LrSO2 levels in both groups, which were not statistically significant at T1, T2, T3, T4. The RrSO2 levels of Group L at T5 were significantly lower than that of Group O. One patient in Group L had an rSO2 value <80% of the baseline value. CONCLUSIONS: Carbon dioxide insufflation during pneumoperitoneum in pediatric patients may not affect cerebral oxygenation under laparoscopic surgery. PMID- 26993414 TI - Bone mineral density loss in thoracic and lumbar vertebrae following radiation for abdominal cancers. AB - PURPOSE: To investigate the relationship between abdominal chemoradiation (CRT) for locally advanced cancers and bone mineral density (BMD) reduction in the vertebral spine. MATERIALS AND METHODS: Data from 272 patients who underwent abdominal radiation therapy from January 1997 to May 2015 were retrospectively reviewed. Forty-two patients received computed tomography (CT) scans of the abdomen prior to initiation and at least twice after radiation therapy. Bone attenuation (in Hounsfield unit) (HU) measurements were collected for each vertebral level from T7 to L5 using sagittal CT images. Radiation point dose was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (Delta%HU) between baseline and post-radiation therapy were computed for each vertebral body. The Delta%HU was compared against radiation dose using Pearson's linear correlation. RESULTS: Abdominal radiotherapy caused significant reduction in vertebral BMD as measured by HU. Patients who received only chemotherapy did not show changes in their BMD in this study. The Delta%HU was significantly correlated with the radiation point dose to the vertebral body (R=-0.472, P<0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R= 0.578, P<0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (beta=0.830) on determining post-RT HU, while number of months post RT (beta=-0.213) and radiation point dose (beta=-1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R=0.883, P<0.001) with the slope of the best linear fit=0.81. Our model's predicted HU were within +/-20 HU of the actual value in 53% of cases, 70% of the predictions were within +/-30 HU, 81% were within +/-40 HU, and 90% were within +/-50 HU of the actual post-RT HU. Four of 42 patients were found to have vertebral body compression fractures in the field of radiation. CONCLUSIONS: Patients who receive abdominal chemoradiation develop significant BMD loss in the thoracic and lumbar vertebrae. Treatment-related BMD loss may contribute to the development of vertebral compression fractures. A predictive model for post-CRT BMD changes may inform bone protective strategies in patients planned for abdominal CRT. PMID- 26993415 TI - First application of a pixel-wise analysis on bladder dose-surface maps in prostate cancer radiotherapy. AB - PURPOSE: To develop a method for investigating local dose effects on the bladder after prostate cancer radiotherapy based on dose-surface maps (DSMs). BACKGROUND AND PURPOSE: DSMs of patients included in a prospective study (DUE01) were generated by virtually cutting bladder contours at the points intersecting the sagittal plane passing through its center-of-mass: maps were laterally normalized and aligned at the posterior inferior point. The average DSMs of patients with/without toxicity, the DSMs of differences and t statistic were used to select regions better discriminating patients with toxicity. A total of 72 patients with no/mild urinary symptoms before radiotherapy and who were treated with moderate hypo-fractionation (2.5-2.65Gy/fr, 70-74Gy) were considered, and the endpoint was an International Prostate Symptoms Score (IPSS)?15 at the end of therapy (IPSSend?15, n=25/72). RESULTS: The DSMs of patients with/without toxicity were significantly different (p<0.05). The percentage of bladder circumference receiving >50-70Gy at 5-7mm from the base was associated with an IPSSend?15 (odds ratios: 1.03-1.07). Different patterns were recognized for specific symptoms. With frequency/urgency, a quasi-threshold effect on the absolute posterior dose at 5-12mm from the base (2Gy equivalent doses=80-82Gy, alpha/beta=3-5Gy) was observed. CONCLUSIONS: Local-dose effects for acute symptoms were detected in a group of patients treated within a moderately hypo fractionated protocol. The results for frequency/urgency were consistent with a threshold effect on the trigone. PMID- 26993416 TI - Quantification of dose uncertainties in cumulated dose estimation compared to planned dose in prostate IMRT. AB - BACKGROUND AND PURPOSE: In prostate IMRT, the objectives were to quantify, for the bladder and the rectum: (i) the dose difference (DD) between the planned dose (PD) and the estimated cumulated dose (ECD) by deformable image registration (DIR); (ii) the dose accumulation uncertainties (DAU). MATERIALS AND METHODS: A series of 24 patients receiving 80Gy in the prostate was used to calculate the ECDpts and the DDpts. To evaluate the DAU, a numerical phantom (ph) simulating deformations of main pelvic organs was used to calculate the ECDph using the same DIR method. A reference cumulated dose (RCDph) was calculated, based on the simulated deformations. The DAUph was defined by the differences between RCDph and ECDph. RESULTS: For the mean dose to the bladder, the standard deviation of DDpts was 6.9Gy (18.1Gy maximum) with a DAUph of 2.7Gy. For the rectum wall, it was 2.0Gy (4.2Gy maximum) with a DAUph of 1.2Gy. Volume differences between PDpts and ECDpts, along the dose-volume histogram, ranged from -30% to +37% and -14% to +14% for the bladder and rectum, respectively. The corresponding uncertainties ranged from -23% to +7% and -4% to +7% for the bladder and rectum, respectively. CONCLUSIONS: Large differences between planned and delivered doses to the bladder have been quantified and are higher than the uncertainties of the DIR method. For the rectum, the differences are smaller and close to the DIR uncertainties. PMID- 26993417 TI - The impact of interfractional anatomical changes on the accumulated dose in carbon ion therapy of pancreatic cancer patients. AB - BACKGROUND AND PURPOSE: We evaluated the robustness of carbon ion therapy for pancreatic cancer patients by investigating the impact of interfractional anatomical changes on the accumulated dose when using bony anatomy- and fiducial marker-based position verification. MATERIAL AND METHODS: Carbon ion treatment plans were created for 9 patients in this retrospective planning study. The planning CT was deformably registered to each daily cone-beam CT (CBCT). The gastrointestinal gas volume visible on each CBCT was copied to these deformed CT images. Subsequently, the fraction doses were calculated by aligning the treatment plan according to a bony anatomy- and a fiducial marker-based registration. We compared the accumulated fraction doses with the planned dose using dose-volume histograms (DVHs) of the internal gross tumour volume (iGTV), internal clinical target volume (iCTV), duodenum, stomach, liver, spinal cord and kidneys. RESULTS: iCTV coverage (D98%) was on average reduced from 98.6% as planned to 81.9% and 88.6% for the bony anatomy- and marker-based registrations, respectively. DVHs of the duodenum showed large differences between the planned and accumulated dose. CONCLUSIONS: Severe reductions in dose coverage of the target due to interfractional anatomical changes were observed in both position verification methods. PMID- 26993418 TI - Phase I trial of 18F-Fludeoxyglucose based radiation dose painting with concomitant cisplatin in head and neck cancer. AB - PURPOSE: The CONTRAST (CONventional vs.Tumor Recurrence Adapted Specification of Target dose) phase I trial tested the safety of FDG PET guided dose redistribution in patients receiving accelerated chemo-radiotherapy for locally advanced head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: CONTRAST was designed with two pre-defined dose-escalation steps to the FDG PET avid volume (GTVPET). The primary end point was any early grade 4+ toxicity according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). The dose to GTVPET was escalated to a uniform prescription of 82Gy EQD2 in the first step. All patients received accelerated radiotherapy (6 fractions a week) delivering 34 fractions of 2.34Gy to the GTVPET as well as concomitant weekly cisplatin. Inclusion criteria were (1) primary SCC of oral cavity, oro- or hypo pharynx, or laynx, (2) candidates for concomitant chemo-radiotherapy and (3) p16 negative tumors or p16 positive tumors in patients with smoking history of >10 pack years. GTVPET was defined by a specialist in nuclear medicine and a radiologist, while the anatomic GTV was defined in collaboration between an oncologist and a radiologist. RESULTS: Median follow up time from the end of treatment was 18months (range 7-21months). All 15 patients completed treatment without interruptions and no incidents of early grade 4+ toxicity were observed. Four patients had ulceration at the evaluation two months after treatment, two have subsequently healed, but two remain, raising concerns regarding late effects. CONCLUSIONS: With all 15 cases having completed four month follow up and no incidence of early grade 4+ toxicity FDG PET based dose escalation to 82Gy passed the protocol-defined criterion for dose escalation. However, two cases of concern regarding late outcome led us to refrain from further dose escalation and proceed with the current dose level in a larger comparative effectiveness trial. PMID- 26993419 TI - To live or let die: Unclear task of autophagy in the radiosensitization battle. AB - Radiation-induced autophagy is believed to represent a radioprotective mechanism of cancer cells. Thus, its inhibition should support radiation treatment and increase its efficacy. On the other hand, there is evidence that radiation alone or in combination with various chemical agents can induce autophagy that results into increased cell death, especially within transformed apoptosis-resistant cells. In this paper, besides description of autophagic process and its relation to cancer and radiotherapy, we compared two contradictory radiosensitization approaches that employ inhibition and induction of autophagy. In spite of the classical concept based on cytoprotective model, there is a plethora of recently developed inducers of autophagy, which indicates the future trend in radiosensitization via modulation of autophagy. Because contemporary literature is conflicting and inconsistent in this respect, we reviewed the recent studies focused on enhancement of sensitivity of cancer cells toward radiation in regard to autophagy, revealing some striking discrepancies. The deeper the knowledge, the more complex this situation is. To interpret results of various studies correctly one has to take into account the methodology of autophagy assessment and also the fact that radiosensitization might be mediated by other than intrinsic mechanisms related to autophagy. Notwithstanding, targeting autophagy remains an attractive anti-tumor strategy. PMID- 26993424 TI - Midcingulate cortex: Structure, connections, homologies, functions and diseases. AB - Midcingulate cortex (MCC) has risen in prominence as human imaging identifies unique structural and functional activity therein and this is the first review of its structure, connections, functions and disease vulnerabilities. The MCC has two divisions (anterior, aMCC and posterior, pMCC) that represent functional units and the cytoarchitecture, connections and neurocytology of each is shown with immunohistochemistry and receptor binding. The MCC is not a division of anterior cingulate cortex (ACC) and the "dorsal ACC" designation is a misnomer as it incorrectly implies that MCC is a division of ACC. Interpretation of findings among species and developing models of human diseases requires detailed comparative studies which is shown here for five species with flat maps and immunohistochemistry (human, monkey, rabbit, rat, mouse). The largest neurons in human cingulate cortex are in layer Vb of area 24 d in pMCC which project to the spinal cord. This area is part of the caudal cingulate premotor area which is involved in multisensory orientation of the head and body in space and neuron responses are tuned for the force and direction of movement. In contrast, the rostral cingulate premotor area in aMCC is involved in action-reinforcement associations and selection based on the amount of reward or aversive properties of a potential movement. The aMCC is activated by nociceptive information from the midline, mediodorsal and intralaminar thalamic nuclei which evoke fear and mediates nocifensive behaviors. This subregion also has high dopaminergic afferents and high dopamine-1 receptor binding and is engaged in reward processes. Opposing pain/avoidance and reward/approach functions are selected by assessment of potential outcomes and error detection according to feedback mediated, decision making. Parietal afferents differentially terminate in MCC and provide for multisensory control in an eye- and head-centric manner. Finally, MCC vulnerability in human disease confirms the unique organization of MCC and supports the predictive validity of the MCC dichotomy. Vulnerability of aMCC is shown in chronic pain, obsessive-compulsive disorder with checking symptoms and attention-deficit/hyperactivity disorder and methylphenidate and pain medications selectively impact aMCC. In contrast, pMCC vulnerabilities are for progressive supranuclear palsy, unipolar depression and posttraumatic stress disorder. Thus, there is an emerging picture of the organization, functions and diseases of MCC. Future work will take this type of modular analysis to individual areas of which there are at least 10 in MCC. PMID- 26993425 TI - Cell-penetrating peptides as noninvasive transmembrane vectors for the development of novel multifunctional drug-delivery systems. AB - Unique characteristics, such as nontoxicity and rapid cellular internalization, allow the cell-penetrating peptides (CPPs) to transport hydrophilic macromolecules into cells, thus, enabling them to execute biological functions. However, some CPPs have limitations due to nonspecificity and easy proteolysis. To overcome such defects, the CPP amino acid sequence can be modified, replaced, and reconstructed for optimization. CPPs can also be used in combination with other drug vectors, fused with their preponderances to create novel multifunctional drug-delivery systems that increase the stability during blood circulation, and also develop novel preparations capable of targeted delivery, along with sustainable and controllable release. Further improvements in CPP structure can facilitate the penetration of macromolecules into diverse biomembrane structures, such as the blood brain barrier, gastroenteric mucosa, and skin dermis. The ability of CPP to act as transmembrane vectors improves the clinical application of some biomolecules to treat central nervous system diseases, increase oral bioavailability, and develop percutaneous-delivery dosage form. PMID- 26993426 TI - Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation. AB - The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-l-ornithine (PLO)-containing microcapsules, liquefied core poly-l-lysine (PLL)-containing microcapsules, and solid core PLL-containing microcapsules. No complement or inflammatory cytokine activation was detected for the Ca/Ba alginate microbeads. Liquefied core PLO- and PLL-containing microcapsules induced significant fluid phase complement activation (TCC), but with low complement surface deposition (anti-C3c), and a low proinflammatory cytokine secretion, with exception of an elevated MCP-1(CCL2) secretion. The solid core PLL-containing microcapsules generated lower TCC but a marked complement surface deposition and significant induction of the proinflammatory cytokines interleukin (IL-1)beta, TNF, IL-6, the chemokines IL-8 (CXCL8), and MIP-1alpha (CCL3) and MCP-1(CCL2). Inhibition with compstatin (C3 inhibitor) completely abolished complement surface deposition, leukocyte adhesion and the proinflammatory cytokines. The C5 inhibitions partly lead to a reduction of the proinflammatory cytokines. The leukocyte adhesion was abolished by inhibitory antibodies against CD18 and partly reduced by CD11b, but not by CD11c. Anti-CD18 significantly reduced the (IL-1)beta, TNF, IL-6 and MIP-1alpha and anti CD11b significantly reduced the IL-6 and VEGF secretion. MCP-1 was strongly activated by anti-CD18 and anti-CD11b. In conclusion the initial proinflammatory cytokine responses are driven by the microspheres potential to trigger complement C3 (C3b/iC3b) deposition, leukocyte activation and binding through complement receptor CR3 (CD11b/CD18). MCP-1 is one exception dependent on the fluid phase complement activation mediated through CR3. PMID- 26993428 TI - Safety and Cost-Effectiveness of Same-Day Cardiac Resynchronization Therapy and Implantable Cardioverter Defibrillator Implantation. AB - Cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillator (ICD) implantation improve morbidity and mortality in selected patients. Many centers still admit patients overnight. We evaluated the safety, feasibility, and cost savings of same-day CRT/ICD device implantation by performing a retrospective study of all consecutive elective CRT/ICD implants at a tertiary center from January 2009 to April 2013. All emergency and/or inpatient cases were excluded. Data were collected on baseline demographics, implantation indication, procedure details, complications (categorized as immediate [<=24 hours], short term [24 hours to 6 weeks], medium term [6 weeks to 4 months], and long term [>4 months]), and mortality (30 day and 1 year). Comparisons were made between those having planned same-day versus overnight stay procedures. A cost analysis was performed to evaluate cost savings of the same-day policy. A total of 491 devices were implanted during this period: 267 were elective (54 planned overnight, 213 planned same-day) of which 229 were CRT pacemakers or CRT defibrillators and 38 ICDs. There were 26 total overall complications (9.7%) with no significant differences between planned same-day versus planned overnight stay cohorts (9.4% vs 11.1%, p = 0.8) and specifically no differences in immediate, short-, medium-, and long-term complications at follow-up. The 30-day and 1-year mortality rates did not differ between the two groups. An overnight stay at our hospital costs $450 (L300); our cost saving during this period was $91,800 (L61,200). Same-day CRT/ICD implantation is safe, feasible, and associated with significant cost savings. It provides significant advantages for patients and health care providers, especially given the current financial climate. PMID- 26993427 TI - Early and Midterm Outcome of Propensity-Matched Intermediate-Risk Patients Aged >=80 Years With Aortic Stenosis Undergoing Surgical or Transcatheter Aortic Valve Replacement (from the Italian Multicenter OBSERVANT Study). AB - The aim of this study was to analyze procedural and postprocedural outcomes of patients aged >=80 years treated by transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) as enrolled in the OBservational Study of Effectiveness of SAVR-TAVR procedures for severe Aortic steNosis Treatment (OBSERVANT) Study. TAVI is offered to patients with aortic stenosis judged inoperable or at high surgical risk. Nevertheless, it is common clinical practice to treat elderly (>=80 years) patients by TAVI regardless of surgical risk for traditional SAVR. OBSERVANT is a multicenter, observational, prospective cohort study that enrolled patients with symptomatic severe aortic stenosis who underwent SAVR or TAVI from December 2010 to June 2012 in 93 Italian participating hospitals. Information on demographic characteristics, health status before intervention, therapeutic approach, and intraprocedural and 30-day outcomes was collected. An administrative follow-up was set up to collect data on midterm to long-term outcomes. We reviewed baseline and procedural data of patients aged >=80 years, looking for different early and late outcome after TAVI or SAVR. Patients treated by TAVI were sicker than SAVR because of higher rate of co-morbidities, advanced illness, frailty, and Logistic EuroSCORE. After propensity matching, early and midterm mortality were comparable between the 2 groups. However, patients treated by TAVI had higher rate of vascular complications (6.0% vs 0.5%; p <0.0001), permanent pacemaker implantation (13.4% vs 3.7%; p <0.0001), and paravalvular leak (8.9% vs 2.4%; p <0.0001). Patients who underwent SAVR had more frequent bleedings needing transfusion (63.2% vs 34.5%; p <0.0001) and acute kidney injury (9.6% vs 3.9%; p = 0.0010). In conclusion, patients aged >=80 years treated by TAVI or SAVR had similar early and midterm mortality. PMID- 26993432 TI - Design of a Tablet Computer App for Facilitation of a Molecular Blood Culture Test in Clinical Microbiology and Preliminary Usability Evaluation. AB - BACKGROUND: User mobility is an important aspect of the development of clinical information systems for health care professionals. Mobile phones and tablet computers have obtained widespread use by health care professionals, offering an opportunity for supporting the access to patient information through specialized applications (apps) while supporting the mobility of the users. The use of apps for mobile phones and tablet computers may support workflow of complex tasks, for example, molecular-based diagnostic tests in clinical microbiology. Multiplex Blood Culture Test (MuxBCT) is a molecular-based diagnostic test used for rapid identification of pathogens in positive blood cultures. To facilitate the workflow of the MuxBCT, a specialized tablet computer app was developed as an accessory to the diagnostic test. The app aims to reduce the complexity of the test by step-by-step guidance of microscopy and to assist users in reaching an exact bacterial or fungal diagnosis based on blood specimen observations and controls. Additionally, the app allows for entry of test results, and communication thereof to the laboratory information system (LIS). OBJECTIVE: The objective of the study was to describe the design considerations of the MuxBCT app and the results of a preliminary usability evaluation. METHODS: The MuxBCT tablet app was developed and set up for use in a clinical microbiology laboratory. A near-live simulation study was conducted in the clinical microbiology laboratory to evaluate the usability of the MuxBCT app. The study was designed to achieve a high degree of realism as participants carried out a scenario representing the context of use for the MuxBCT app. As the MuxBCT was under development, the scenario involved the use of molecular blood culture tests similar to the MuxBCT for identification of microorganisms from positive blood culture samples. The study participants were observed, and their interactions with the app were recorded. After the study, the participants were debriefed to clarify observations. RESULTS: Four medical laboratory technicians, for example, representative of end users of the app, participated in the clinical simulation study. Using the MuxBCT app, the study participants successfully identified and reported all microorganisms from the positive blood cultures examined. Three of the four participants reported that they found the app useful, while one study participant reported that she would prefer to make notes on paper and later enter them into the LIS. CONCLUSIONS: The preliminary usability evaluation results indicate that use of the MuxBCT tablet app can facilitate the workflow of the MuxBCT diagnostic test. PMID- 26993433 TI - Novel WASP mutation in a patient with Wiskott-Aldrich syndrome: Case report and review of the literature. AB - BACKGROUND: The Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive immunodeficiency disorder, caused by mutations in the WAS protein (WASP) gene and characterised by thrombocytopenia, small platelets, eczema, and recurrent infections associated with increased risk of autoimmunity and malignancy disorders. The gene for WAS has been mapped to the short arm of the X chromosome at Xp 11.22-23 and early detection of patients and diagnosis of new mutation might reduce related complications and increase their life expectancy. METHOD AND RESULT: We found a novel mutation by sequence analysis of genomic DNA coding of a 9-month old boy suffering from WAS. The mutation was insertion G in exon 10 of WASP gene. The consequence of the G insertion is a premature stop immediately at amino acid 335 (N335X or p.G334GfsX1) and truncated protein. CONCLUSION: The mutation analysis is helpful for the diagnosis of WAS patients and also expanding the spectrum of WASP mutations for carrier detection and prenatal diagnosis. PMID- 26993435 TI - Challenges of modifying disease progression in prediagnostic Parkinson's disease. AB - Neurodegeneration in Parkinson's disease starts years before a clinical diagnosis can be reliably made. The prediagnostic phase of the disease offers a window of opportunity in which disease-modifying therapies-ie, those aimed at delaying or preventing the progression to overt disease and its many complications-could be most beneficial, but no such therapies are available at present. The unravelling of the mechanisms of neurodegeneration from the earliest stages, however, could lead to the development of new interventions whose therapeutic potential will need to be assessed in adequately designed clinical trials. Advances in the understanding of this prediagnostic phase of Parkinson's disease (for which the clinical diagnostic and prognostic markers used in more advanced disease stages are not applicable) will lead to the identification of biomarkers of neurodegeneration and its progression. These biomarkers will, in turn, help to identify the optimum population to be included and the most appropriate outcomes to be assessed in trials of disease-modifying drugs. Potential risks to minimally symptomatic participants, some of whom might not progress to manifest Parkinson's disease, and individuals who do not wish to know their mutation carrier status, could pose specific ethical dilemmas in the design of these trials. PMID- 26993434 TI - Coronary CT angiography derived morphological and functional quantitative plaque markers correlated with invasive fractional flow reserve for detecting hemodynamically significant stenosis. AB - OBJECTIVE: Compare morphological and functional coronary plaque markers derived from coronary CT angiography (CCTA) for their ability to detect lesion-specific ischemia. MATERIALS AND METHODS: Data of patients who had undergone both dual source CCTA and invasive fractional flow reserve (FFR) measurement within 3 months were retrospectively analyzed. Various quantitative stenosis markers were derived from CCTA: Corrected coronary opacification (CCO), transluminal attenuation gradient (TAG), remodeling index (RI), computational FFR (cFFR), lesion length (LL), vessel volume (VV), total plaque volume (TPV), and calcified and non-calcified plaque volume (CPV and NCPV). Discriminatory power of these markers for flow-limiting versus non-significant coronary stenosis was assessed against invasive FFR as the reference standard. RESULTS: The cohort included 37 patients (61 +/- 12 years, 68% male). Among 37 lesions, 11 were hemodynamically significant by FFR. On a per-lesion level, sensitivity and specificity of TPV, CPV, and NCPV for hemodynamically significant stenosis detection were 88% and 74%, 67% and 53%, and 92% and 81%, respectively. For CCO, TAG, RI, and cFFR these were 64% and 86%, 35% and 56%, 82% and 54%, and 100% and 90%, respectively. At ROC analysis, only TPV (0.78, p = 0.013), NCPV (0.79, p = 0.009), cFFR (0.85, p = 0.003), and CCO (0.82, p = 0.0003) showed discriminatory power for detecting hemodynamically significant stenosis. CONCLUSION: TPV, NCPV, CCO, and cFFR derived from CCTA can aid detecting hemodynamically significant coronary lesions with cFFR showing the greatest discriminatory ability. PMID- 26993436 TI - Zika fever. AB - Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barre syndrome. PMID- 26993438 TI - [Skin infection due to Gordonia araii]. PMID- 26993437 TI - [Contributions to article "Recurrent disease due to rybotipe 027 Clostridium difficile"]. PMID- 26993440 TI - Fight against antibiotic resistance 'must start on farms'. PMID- 26993439 TI - Streptococcus salivarius spontaneous bacterial peritonitis in a HIV/HCV-co infected patient treated with direct antiviral agents. PMID- 26993441 TI - Bovine TB: further cattle measures to be introduced in England. PMID- 26993442 TI - FVE welcomes new animal health law. PMID- 26993444 TI - Practical guidance on chronic kidney disease in cats. PMID- 26993445 TI - Guide to help practices get to grips with compulsory microchipping. PMID- 26993446 TI - Bovine heart makes shortlist for imaging awards. PMID- 26993447 TI - Celebrations--and controversy--at the 125th Crufts dog show. PMID- 26993448 TI - Working together to achieve the best outcomes for equine health and welfare. AB - Gill Harris reports from this year's National Equine Forum where a key theme was the importance of collaboration and effective communication in achieving the best outcomes for the health and welfare of the horse and the future of equestrianism in the UK. PMID- 26993449 TI - Students offer treatment for pets on the streets. PMID- 26993450 TI - Pneumonia outbreaks in calves and finishers. AB - Pneumonia in calves and finishers. Ovarian tumour in a calf . Abortion associated with bovine herpesvirus 1 in a suckler herd. Parasitic gastroenteritis causing illthrift and death in sheep. Outbreaks of acute fasciolosis in sheep. These are among matters discussed in the disease surveillance report for December 2015 from SAC Consulting: Veterinary Services (SAC C VS). PMID- 26993451 TI - Coinfection with type 1 and type 2 PRRSV. PMID- 26993452 TI - Think ahead: safety first for equine vets. AB - Working with horses is dangerous. Jill Butterworth believes that wearing a hard hat could make all the difference. PMID- 26993453 TI - Recognition of EU veterinary qualifications. PMID- 26993454 TI - Managing conspecific overgrooming in rabbits. PMID- 26993455 TI - Study on canine total elbow replacement. PMID- 26993456 TI - Somulose solution for injection. PMID- 26993457 TI - Vets and public health. PMID- 26993458 TI - Treatment of clinical mastitis in dairy cattle. PMID- 26993459 TI - Wild animal welfare. PMID- 26993460 TI - Global issues put a new perspective on working life. AB - Having worked in general practice, Josep Subirana decided to broaden his experience in animal welfare and get involved in international development. Since then, he has worked across the world helping charities, universities and organisations with animal welfare issues. PMID- 26993461 TI - Ten-minute chat. AB - In her second year of vet school Cheryl Scudamore found she enjoyed pathology and biological research and decided that practice might not be for her. Now working in biomedical science as a pathologist she supports studies into the genetic basis of human diseases. PMID- 26993462 TI - Structural and molecular basis of cellulase Cel48F by computational modeling: Insight into catalytic and product release mechanism. AB - As a processive cellulase, Cel48F from Clostridium cellulolyticum plays a crucial role in cellulose fiber degradation. It has been confirmed in experiment that residue Glu44 will greatly affect the catalytic activity but the mechanism is still unknown. In this study, conventional molecular dynamics, steered molecular dynamics and free energy calculation were integrated to simulate the hydrolysis and product release process to gain insights into the factors that influence catalytic activity. Analysis of simulation results indicated that Glu44 could maintain the proper conformation of its substrate to ensure successful cleavage reaction or serve as a base required in the inverting mechanism in hydrolysis. After hydrolysis is completed, residues Glu44, Asp494, Trp611 and Glu55 participate in hydrogen bond rearrangement during product releasing process. This rearrangement can reduce the sliding barrier and stimulate the product to move toward the exit in the initial release stage. Dependent on the rearrangement, the product moves toward the exit and is exposed to an increasing amount of solvent molecules, which makes solvent effect more and more notable. With the assistance of solvent interaction, product can get rid of the enzyme more easily. However, the subsequent release process remains uncertain because of the disordered motion of solvent molecules. This work provides theoretical data as a basis of cellulase modification or mutation. PMID- 26993463 TI - Structural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B. AB - DNA methylation is an important epigenetic modification involved in chromatin organization and gene expression. The function of DNA methylation depends on cell context and is correlated with histone modification patterns. In particular, trimethylation of Lys36 on histone H3 tail (H3K36me3) is associated with DNA methylation and elongation phase of transcription. PWWP domains of the de novo DNA methyltransferases DNMT3A and DNMT3B read this epigenetic mark to guide DNA methylation. Here we report the first crystal structure of the DNMT3B PWWP domain H3K36me3 complex. Based on this structure, we propose a model of the DNMT3A PWWP domain-H3K36me3 complex and build a model of DNMT3A (PWWP-ADD-CD) in a nucleosomal context. The trimethylated side chain of Lys36 (H3K36me3) is inserted into an aromatic cage similar to the "Royal" superfamily domains known to bind methylated histones. A key interaction between trimethylated Lys36 and a conserved water molecule stabilized by Ser270 explains the lack of affinity of mutated DNMT3B (S270P) for the H3K36me3 epigenetic mark in the ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome. The model of the DNMT3A-DNMT3L heterotetramer in complex with a dinucleosome highlights the mechanism for recognition of nucleosome by DNMT3s and explains the periodicity of de novo DNA methylation. PMID- 26993464 TI - In vivo modified organic matrix for testing biomineralization-related protein functions in differentiated Dictyostelium on calcite. AB - This work reports an in vivo approach for identifying the function of biomineralization-related proteins. Synthetic sequences of n16N, OC-17 and perlucin with signal peptides are produced in a novel Gateway expression system for Dictyostelium under the control of the [ecmB] promoter. A fast and easy scanning electron microscopic screening method was used to differentiate on the colony level between interplay effects of the proteins expressed in the extracellular matrix (ECM). Transformed Dictyostelium, which migrated as multicellular colonies on calcite crystals and left their ECM remnants on the surface were investigated also by energy-dispersive X-ray spectroscopy (EDX). Calcium minerals with and without phosphorous accumulated very frequently within the matrix of the Dictyostelium colonies when grown on calcite. Magnesium containing phosphorous granules were observed when colonies were exposed on silica. The absence of calcium EDX signals in these cases suggests that the external calcite crystals but not living cells represent the major source of calcium in the ECM. Several features of the system provide first evidence that each protein influences the properties of the matrix in a characteristic mode. Colonies transformed with perlucin produced a matrix with cracks on the length scale of a few microns throughout the matrix patch. For colonies with OC-17, almost no cracks were observed, regardless of the length scale. The non transformed Dictyostelium (Ax3-Orf+) produced larger cracks. The strategy presented here develops the first step toward an efficient eukaryotic screening system for the combinatorial functionalization of materials by bioengineering in close analogy to natural biomineralization concepts. PMID- 26993466 TI - Extreme delta brushes and BIRDs in the EEG of anti-NMDA-receptor encephalitis. PMID- 26993465 TI - Structural insights into the regulation of NADPH binding to reductase domains of nonribosomal peptide synthetases: A concerted loop movement model. AB - The termination module of nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) offloads the final product as an acid (occasionally also accompanied by cyclization) upon hydrolysis by employing thioesterase domains (TE domains). Reductase domains (R-domains) of short-chain dehydrogenase/reductase (SDR) family offer an alternative offloading mechanism by reducing 4' phosphopantetheine (4'-PPant) arm-tethered peptidyl chain, a thioester, to an aldehyde or an alcohol. Recent studies have highlighted their functional importance, for instance in the glycopeptidolipid (GPL) biosynthesis of Mycobacterium smegmatis, where the resulting alcoholic group is the site for subsequent modifications such as glycosylations. The mechanistic understanding of how these R-domains function in the context of multi-modular NRPS and PKS is poorly understood. In this study, conformational differences in functionally important loops, not reported previously, were identified in a new crystal form of R-domain which may be relevant to functioning in the context of assembly-line NRPS and PKS enzymology. Here, we propose a concerted loop movement model that allows gating of cofactor binding to these enzymes, enabling the release of the final product only after the substrate has reached the active site during biosynthesis, and therefore distinct from a canonical single domain SDR family of enzymes. PMID- 26993468 TI - Development of an isothermoal amplification-based assay for rapid visual detection of an Orf virus. AB - BACKGROUND: Orf virus (ORFV) is the causative agent of a severe infectious skin disease (also known as contagious ecthyma) in goats, sheep and other small ruminants. Importantly, ORFV also infect humans which causes a public health concern in the context of changing environment and increase in human populations. The rapid detection is critical in effective control of the disease and urgently needed. RESULTS: A novel "point of care" molecular amplification assay for rapid visual detection of ORFV was developed based on isothermoal recombinase polymerase amplification (RPA) technology in combination with a simpler lateral flow immunoassay strip (ORFV RPA- LFD assay). The developed ORFV RPA- LFD assay was able to detect ORFV in less than 25 min. This assay was highly sensitive, with detection limit of as low as 80 copies/reaction, and highly specific, with no cross-reactions with capripox virus, foot-and-mouth disease virus and peste des petits ruminants virus. Furthermore, the ORFV RPA- LFD assay has good correlation with qPCR assay for detection of ORFV present in clinical samples. CONCLUSIONS: The developed ORFV RPA-LFD assay was a sensitive and specific method for rapid detection of ORFV, and has great potential as an onsite molecular diagnostic tool in control of Orf. PMID- 26993467 TI - Genome-wide Identification and analysis of the stress-resistance function of the TPS (Trehalose-6-Phosphate Synthase) gene family in cotton. AB - BACKGROUND: Trehalose (a-D-glucopyranosyl a-D-glucopyranoside) is a nonreducing disaccharide and is widely distributed in bacteria, fungi, algae, plants and invertebrates. In the study, the identification of trehalose-6-phosphate synthase (TPS) genes stress-related in cotton, and the genetic structure analysis and molecular evolution analysis of TPSs were conducted with bioinformatics methods, which could lay a foundation for further research of TPS functions in cotton. RESULTS: The genome information of Gossypium raimondii (group D), G. arboreum L. (group A), and G. hirsutum L. (group AD) was used in the study. Fifty-three TPSs were identified comprising 15 genes in group D, 14 in group A, and 24 in group AD. Bioinformatics methods were used to analyze the genetic structure and molecular evolution of TPSs. Real-time PCR analysis was performed to investigate the expression patterns of gene family members. All TPS family members in cotton can be divided into two subfamilies: Class I and Class II. The similarity of the TPS sequence is high within the same species and close within their family relatives. The genetic structures of two TPS subfamily members are different, with more introns and a more complicated gene structure in Class I. There is a TPS domain(Glyco transf_20) at the N-terminal in all TPS family members and a TPP domain(Trehalose_PPase) at the C-terminal in all except GrTPS6, GhTPS4, and GhTPS9. All Class II members contain a UDP-forming domain. The responses to environmental stresses showed that stresses could induce the expression of TPSs but the expression patterns vary with different stresses. CONCLUSIONS: The distribution of TPSs varies with different species but is relatively uniform on chromosomes. Genetic structure varies with different gene members, and expression levels vary with different stresses and exhibit tissue specificity. The upregulated genes in upland cotton TM-1 is significantly more than that in G. raimondii and G. arboreum L. Shixiya 1. PMID- 26993469 TI - Adaptive designs undertaken in clinical research: a review of registered clinical trials. AB - Adaptive designs have the potential to improve efficiency in the evaluation of new medical treatments in comparison to traditional fixed sample size designs. However, they are still not widely used in practice in clinical research. Little research has been conducted to investigate what adaptive designs are being undertaken. This review highlights the current state of registered adaptive designs and their characteristics. The review looked at phase II, II/III and III trials registered on ClinicalTrials.gov from 29 February 2000 to 1 June 2014, supplemented with trials from the National Institute for Health Research register and known adaptive trials. A range of adaptive design search terms were applied to the trials extracted from each database. Characteristics of the adaptive designs were then recorded including funder, therapeutic area and type of adaptation. The results in the paper suggest that the use of adaptive designs has increased. They seem to be most often used in phase II trials and in oncology. In phase III trials, the most popular form of adaptation is the group sequential design. The review failed to capture all trials with adaptive designs, which suggests that the reporting of adaptive designs, such as in clinical trials registers, needs much improving. We recommend that clinical trial registers should contain sections dedicated to the type and scope of the adaptation and that the term 'adaptive design' should be included in the trial title or at least in the brief summary or design sections. PMID- 26993470 TI - Pharmacogenetics of Lipid-Lowering Agents: Precision or Indecision Medicine? AB - Lipid-lowering medications, particularly statins, have been a popular target for pharmacogenetic studies. A handful of genes have shown promise for predicting response to therapy from the perspective of lipid lowering, as well as myopathy. A number of genes have been implicated and have biological plausibility based on their involvement with the pharmacokinetics or pharmacodynamics of statins or other lipid-lowering medications. The level of confidence and replication of these findings varies, although several associations are likely true. Novel classes of lipid-lowering therapy have opened up new possibilities in the treatment of severe inherited forms of dyslipidemia, making the identification of such mutations an important pharmacogenetic predictor of failure of standard therapy, with potential response to novel therapy. Advances in next-generation sequencing technology bring the application of pharmacogenetics even closer to routine clinical practice. PMID- 26993471 TI - Incentives in Diabetic Eye Assessment by Screening (IDEAS): study protocol of a three-arm randomized controlled trial using financial incentives to increase screening uptake in London. AB - BACKGROUND: Diabetes is an increasing public health problem in the UK and globally. Diabetic retinopathy is a microvascular complication of diabetes, and is one of the leading causes of blindness in the UK working age population. The diabetic eye screening programme in England aims to invite all people with diabetes aged 12 or over for retinal photography to screen for the presence of diabetic retinopathy. However, attendance rates are only 81 %, leaving many people at risk of preventable sight loss. METHODS: This is a three arm randomized controlled trial to investigate the impact of different types of financial incentives (based on principles from behavioral economics) on increasing attendance at diabetic eye screening appointments in London. Eligible participants will be aged 16 or over, and are those who have been invited to screening appointments annually, but who have not attended, or telephoned to rearrange an appointment, within the last 24 months. Eligible participants will be randomized to one of three conditions: 1. Control condition (usual invitation letter) 2. Fixed incentive condition (usual invitation letter, including a voucher for L10 if they attend their appointment) 3. Probabilistic incentive condition (invitation letter, including a voucher for a 1 in 100 chance of winning L1000 if they attend their appointment). Participants will be sent invitation letters, and the primary outcome will be whether or not they attend their appointment. One thousand participants will be included in total, randomized with a ratio of 1.4:1:1. In order to test whether the incentive scheme has a differential impact on patients from different demographic or socio economic groups, information will be recorded on age, gender, distance from screening center, socio-economic status and length of time since they were last screened. A cost-effectiveness analysis will also be performed. DISCUSSION: This study will be the first trial of financial incentives for improving uptake of diabetic eye screening. If effective, the intervention may suggest a cost effective way to increase screening rates, thus reducing unnecessary blindness. TRIAL REGISTRATION: ISRCTN14896403, 25 February 2016. PMID- 26993473 TI - The application of a biometric identification technique for linking community and hospital data in rural Ghana. AB - BACKGROUND: The reliability of counts for estimating population dynamics and disease burdens in communities depends on the availability of a common unique identifier for matching general population data with health facility data. Biometric data has been explored as a feasible common identifier between the health data and sociocultural data of resident members in rural communities within the Kintampo Health and Demographic Surveillance System located in the central part of Ghana. OBJECTIVE: Our goal was to assess the feasibility of using fingerprint identification to link community data and hospital data in a rural African setting. DESIGN: A combination of biometrics and other personal identification techniques were used to identify individual's resident within a surveillance population seeking care in two district hospitals. Visits from resident individuals were successfully recorded and categorized by the success of the techniques applied during identification. The successes of visits that involved identification by fingerprint were further examined by age. RESULTS: A total of 27,662 hospital visits were linked to resident individuals. Over 85% of those visits were successfully identified using at least one identification method. Over 65% were successfully identified and linked using their fingerprints. Supervisory support from the hospital administration was critical in integrating this identification system into its routine activities. No concerns were expressed by community members about the fingerprint registration and identification processes. CONCLUSIONS: Fingerprint identification should be combined with other methods to be feasible in identifying community members in African rural settings. This can be enhanced in communities with some basic Demographic Surveillance System or census information. PMID- 26993472 TI - Biomechanical evaluation of monosegmental pedicle instrumentation in a calf spine model and the role of fractured vertebrae in screw stability. AB - BACKGROUND: Monsegmental pedicle instrumentation (MSPI) has been used to treat thoracolumbar fractures. However, there are few reports about the biomechanical characteristics of MSPI compared with traditional short-segment pedicle instrumentation (SSPI) in management of unstable thoracolumbar fractures, and the influence of vertebral fracture on screw stability is still unclear. METHODS: This study was to compare the immediate stability between MSPI and SSPI in management of unstable L1 fracture, and to evaluate the role of fractured vertebrae in screw stability. Two studies were performed: in the first study, sixteen fresh calf spines (T11-L3) were divided into two groups, in which unstable fractures at L1 were produced and then instrumented with MSPI or SSPI respectively. The range of motion (ROM) and lax zone (LZ) of specimens were evaluated with pure moment of 6 Nm loaded. The second study measured and compared the pullout strength of screws inserted in to 16 intact and fractured vertebrae of calf spines (L1-3) respectively. The correlation of pullout strength with load sharing classification (LSC) of fractured vertebrae was analyzed. RESULTS: No significant difference in the ROM and LZ of the destabilized segments after fixation between MSPI and SSPI, except in axial rotation of ROM (P < 0.05). After fatigue cyclic loading, the MSPI showed a significant increase of ROM during lateral bending and axial rotation (P < 0.05); however, there were no significant differences in the LZ during all loading models between groups (P > 0.05). The mean pullout strength of pedicle screws in fractured vertebrae decreased by 13.7%, compared with that of intact vertebrae (P > 0.05), and had a low correlation with LSC of the fractured vertebrae (r = 0.293, P > 0.05). CONCLUSIONS: MSPI can provide effective immediate stability for management of unstable thoracolumbar fractures; however, it has less fatigue resistance during lateral bending and axial rotation compared with SSPI. LSC score of fractured vertebrae is not a major influence on the pullout strength of screws. PMID- 26993474 TI - Regional and directional compliance of the healthy aorta: an ex vivo study in a porcine model. AB - OBJECTIVES: To gain differential knowledge about the physiological compliance and wall strength of the different regions of the aorta, including the ascending aorta, arch and descending aorta in both the circumferential and longitudinal directions, and to generate a hypothesis on the pathophysiological mechanisms that lead to Type A aortic dissection. METHODS: Fresh tissue specimens from 22 ex vivo porcine aortas were analysed on a tensile tester. Regional and directional compliance, failure stress and failure strain were recorded. RESULTS: Aortic compliance appeared as a linear function of the natural logarithm (ln) of wall stress. Compliance significantly decreased along the length of the aorta. In the ascending aorta, longitudinal compliance significantly (P = 0.003) exceeded circumferential compliance, and the outer curvature was more compliant than the inner curvature (P = 0.03). In the descending aorta, this relationship is reversed: the circumferential compliance exceeded the longitudinal compliance, and the outer aspect was more compliant (P = 0.003). The median circumferential failure stress of all aortic segments was in the range of 2000-2750 kPa, whereas the longitudinal failure stress in the ascending aorta and the arch had values of 750-1000 kPa, which were significantly lower (P < 0.05). Surprisingly, the longitudinal failure stress of the inner aspect of the descending aorta was extraordinarily high (2000 kPa). Failure strain, similar to compliance, was highest in the ascending aorta and decreased along the aorta. CONCLUSION: The aorta appears to be a complex organ with distinct regional and directional differences in compliance and wall strength that is designed to effectively absorb the kinetic energy of cardiac systole and to cushion the momentum of systolic impact. Under normotensive conditions and a preconditioned physiological morphology, the aortic wall works in the steep part of the logarithmic strain stress function; under hypertensive conditions and pathological morphology, the wall reacts in an non-compliant manner. The high longitudinal compliance and low failure stress of the ascending aorta and subsequent pathological changes may be the main determinants of the recurrent patho-anatomy of Type A aortic dissection. PMID- 26993475 TI - Conservative approaches for HeartWare ventricular assist device pump thrombosis may improve the outcome compared with immediate surgical approaches. AB - PURPOSE: Left ventricular assist device (LVAD) pump thrombosis is one of the devastating complications following mechanical circulatory support implantation. Surgical pump exchange is a known high-risk surgery with a high perioperative mortality rate. We aim to summarize our experience with several other alternative approaches in patients with suspected HeartWare HVAD (HeartWare, Framingham, MA, USA) pump thrombosis. METHODS: The outcome of HeartWare HVAD implantations performed at single institution from January 2010 to September 2015 was studied. Inclusion criteria were patients with suspected HeartWare HVAD pump thrombosis. Patients' preoperative characteristics and outcome following various interventions were reviewed. RESULTS: A total of 94 HeartWare HVAD pumps were implanted in 91 patients. The inclusion criteria were met by 13 patients (14%) with a mean age of 55 +/- 14 years old and a median total pump support duration of 467 days (11-937 days). A conservative approach using systemic thrombolysis (recombinant tissue plasminogen activator) + heparin was used in the majority of the patients (15 events = 65%). Heart transplantation was performed in 4 patients and device explantation in 2 patients. Other approaches were used in the rest of patients. Considering thrombolysis-related complications, 1 patient required resternotomy for bleeding after thrombolysis, which was necessary a few days after LVAD implant surgery and 2 patients developed minor intracranial bleeding after thrombolysis. One-year survival after the latest intervention was 69%. CONCLUSIONS: This report showed the feasibility of several alternative conservative approaches combining medications, minimally invasive and interventional methods for patients with HeartWare pump thrombosis. The outcome may be better than immediate surgical pump exchange. PMID- 26993476 TI - Surgical treatment for primary pulmonary lymphoepithelioma-like carcinoma. AB - OBJECTIVES: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare but unique subtype of non-small-cell lung cancer (NSCLC). Our study aimed to evaluate clinicopathological characteristics and the value of surgical treatment for LELC and explore the relevant prognostic factors in a relatively large cohort. METHODS: We retrospectively reviewed the medical records of 39 lung LELC patients who underwent pulmonary resection with curative intent between January 2009 and December 2013. The clinical and pathological characteristics, survival data and relevant prognostic factors were analysed. RESULTS: The median age of lung LELC patients was 47 years (36-81), and 32 of 39 patients were non-smokers (82.1%). Positive expression of P63 and CK5/6 was shown in all the tested LELC specimens. In situ hybridization of Epstein-Bar virus-encoded RNA (EBER) was performed in 36 patients and all of them were positive. However, epidermal growth factor receptor (EGFR) mutational analysis was done in 19 patients and all of them were wild-type. The median follow-up time was 26.0 months in our cohort, and 6-, 12-, 24- and 36-month recurrence-free survival (RFS) rates were 92, 82, 73 and 73%, respectively. Patients with positive lymph nodes experienced significantly worse postoperative RFS than those with negative ones (P = 0.002). Multivariate survival analysis confirmed that only lymph node involvement [RR 0.051; 95% confidence interval, 0.003-0.991, P = 0.049] was an independent prognostic factor. CONCLUSIONS: Primary lung LELC is closely associated with Epstein-Bar virus infection but not involved in EGFR mutation pathway. Radical surgery could achieve a good outcome for resectable pulmonary LELC, and regional lymph node status is a vital prognostic factor. PMID- 26993477 TI - Long-term echocardiographic follow-up of untreated 2+ functional tricuspid regurgitation in patients undergoing mitral valve surgery. AB - OBJECTIVES: Concomitant tricuspid valve surgery with mitral valve surgery is recommended for patients with severe functional tricuspid regurgitation (TR). However, the treatment for 2+ TR (mild TR) remains controversial. Here, we evaluated the long-term results of untreated 2+ TR in patients undergoing mitral valve surgery. METHODS: We retrospectively reviewed the records of 96 patients with untreated 2+ TR among 885 patients who underwent mitral valve surgery from 2003 to 2010. Exclusion criteria were tricuspid valve surgery (TVS), emergency surgery, primary TR and pacemaker lead through the tricuspid valve. We assessed survival and freedom from heart failure. The freedom from 3+ (moderate) or 4+ (severe) TR was investigated by echocardiographic data at pre- and postoperative week 1, then at 1, 3, 5, 7 and 10 postoperative years, which were compared with those in patients who had 2+ TR preoperatively and underwent concomitant TVS in the same period (n = 47). RESULTS: The mean follow-up was 7.1 +/- 2.7 years. There was no 30-day mortality. The survival rate was 97.5% at 5 years and 87.5% at 10 years. The independent risk factors for mortality were age (OR 1.2, P = 0.03) and left ventricular ejection fraction (OR 0.9, P = 0.03). Untreated 2+ TR improved transiently within the first postoperative year (P < 0.001), but progressed again in the mid- to long term. Freedom from >=3+ TR was 64.2% at 5 years and 46.7% at 10 years, which was significantly lower than that from >=3+ TR in patients who underwent concomitant TVS (P = 0.006). The independent risk factors for TR progression (>=3 + TR) were age (OR 1.1, P = 0.005), atrial fibrillation (OR 2.2, P = 0.04) and tricuspid annular diameter (TAD) index (mm/m(2); OR 1.1, P = 0.02). Receiver operating characteristic curves showed that the optimal TAD index cut-off value was 21.0 for long-term survival [area under the curve (AUC) = 0.72] and 21.2 for TR progression (AUC = 0.64). CONCLUSIONS: Although untreated, 2+ TR significantly improved after mitral valve surgery, it then progressed again in the mid- to long term. Therefore, concomitant TVS should be considered in patients with 2+ TR who have dilated tricuspid annulus or atrial fibrillation, if feasible. PMID- 26993478 TI - Cardiac and arterial elastance and myocardial wall stress in children with pectus excavatum. AB - OBJECTIVES: Pectus excavatum (PE) is one of the most common skeletal deformities of childhood. The study was undertaken to assess cardiac functions in children with PE. METHODS: Echocardiography was performed on 32 children with PE and 40 age-matched healthy controls. The following parameters were monitored: meridional left ventricular (LV) wall stress (WSM), arterial elastance (Ea), LV elastance at end-systole derived by single beat (Ees(sb)), LV circumferential end-systolic wall stress (ESWSc), midwall shortening fraction (SFmid), predicted midwall fiber shortening for a measured fiber stress (midwall VCFc), myocardial fiber stress (MFS), LV end-systolic dimension (LVES), LV end-diastolic dimension (LVED) and end-systolic blood pressure (Pes), LV wall thickness at end-systole (hes). To assess the severity of PE, Haller index (HI) was calculated by computed tomography of the thorax. RESULTS: SFmid, ESWSc, midwall VCFc and MFS were lower in PE children than in controls. The degree to which the parameters SFmid, ESWSc, midwall VCFc and MFS were altered in PE children was 14.9, 27.5, 20.3 and 20.3%, respectively. The minimum HI value of children with PE was 2.00, the maximum value was 4.93 and the arithmetic mean was 2.62 +/- 0.56. Of the 32 children, 14 (43.75%) demonstrated mild deformity, 15 (46.88%) showed moderate and only 3 (9.37%) had severe deformity. In children with PE, there was no statistically significant correlation between the cardiac data (ESWSc, midwall VCFc, MFS, Ea, Ees(sb), LVES, LVED, Pes, hes) and HI. CONCLUSION: We found ESWSc, MFS, midwall VCFc and SFmid to be lower in children with PE than in controls. We concluded that the myocardial contractility and afterload is affected in children with PE. PMID- 26993479 TI - Flexible band versus rigid ring annuloplasty for functional tricuspid regurgitation: two different patterns of right heart reverse remodelling. AB - OBJECTIVES: Annuloplasty bands and rings are widely used to treat functional tricuspid regurgitation (TR). However, the question as to which is the ideal annuloplasty device remains open. Early and late outcomes of tricuspid valve annuloplasty with flexible band (B-TVA) or rigid ring (R-TVA) are compared in the present study. METHODS: Between 1999 and 2014, 462 consecutive patients (mean age, 69.2 +/- 9.5 years) with grade >=1+ functional TR (graded from 0 to 3+) underwent either B-TVA (n = 345; mean EuroSCORE II 9.2 +/- 10.8%) or R-TVA (n = 117; mean EuroSCORE II 12 +/- 13.4%) in addition to other cardiac procedures at the authors' institution. RESULTS: One-to-one propensity score-matched analysis resulted in 98 pairs with similar baseline characteristics and operative risk. Hospital mortality was 7.5% after B-TVA and 12% after R-TVA (P = 0.14). R-TVA was associated with higher rates of low cardiac output (10.1 vs 17.9%, P = 0.025) and transient complete atrioventricular block (10.3 vs 17.2%, P = 0.046). Among the matched pairs, there were no significant differences in hospital mortality (5.1 vs 9.2%, P = 0.27) and perioperative complications. Both in overall series and matched pairs, between B-TVA and R-TVA patients, there were no significant differences in freedom from all-cause death (P = 0.29 and 0.91), cardiac and cerebrovascular deaths (P = 0.63 and 0.87) and grade >=2+ TR (P = 0.68 and 0.77). Right atrial and tricuspid valve reverse remodelling combined with right ventricular reverse remodelling occurred after R-TVA but not after B-TVA. CONCLUSIONS: B-TVA and R-TVA are equally effective in the treatment of functional TR. However, R-TVA causes over time a more complete right heart reverse remodelling. PMID- 26993480 TI - Application of a Mass Spectrometric Approach to Detect the Presence of Fatty Acid Biosynthetic Phosphopeptides. AB - The details of plant lipid metabolism are relatively well known but the regulation of fatty acid production at the protein level is still not understood. Hence this study explores the importance of phosphorylation as a mechanism to control the activity of fatty acid biosynthetic enzymes using low and high oleic acid mesocarps of oil palm fruit (Elaeis guineensis variety of Tenera). Adaptation of neutral loss-triggered tandem mass spectrometry and selected reaction monitoring to detect the neutral loss of phosphoric acid successfully found several phosphoamino acid-containing peptides. These peptides corresponded to the peptides from acetyl-CoA carboxylase and 3-enoyl-acyl carrier protein reductase as identified by their precursor ion masses. These findings suggest that these enzymes were phosphorylated at 20th week after anthesis. Phosphorylation could have reduce their activities towards the end of fatty acid biosynthesis at ripening stage. Implication of phosphorylation in the regulation of fatty acid biosynthesis at protein level has never been reported. PMID- 26993481 TI - In vitro elimination of gaseous microemboli utilizing hypobaric oxygenation in the Terumo(r) FX15 oxygenator. AB - BACKGROUND: This study examines the efficacy of hypobaric oxygenation as it relates to the elimination of gaseous microemboli (GME) at designated flow, pressure and temperature combinations. METHODS: Hypobaric oxygenation was employed for experimental trials (n=60), but not for control trials (n=60), while circuit design, data measurements and testing conditions were maintained for both settings. Hypobaric oxygenation conditions were created by applying 100% oxygen at sub-atmospheric sweep gas pressures of 0.67 atmospheres to the gas phase of an integrated hollow-fiber microporous membrane oxygenator. GME were quantified using an Emboli Detection and Classification system (EDAC), while a continuous air infusion, at a rate of 100 ml/min, was applied to the circuit. Trials were conducted at 37 degrees C, 28 degrees C, and 18 degrees C and at two flow and line pressure combinations of: 3.5 L/min & 150 mmHg and 5 L/min & 200 mmHg. RESULTS: Sub-atmospheric sweep gas pressures allowed adequate oxygenation independent of carbon dioxide removal while significantly reducing the potential entrance of nitrogen into the blood. GME was reduced significantly across all temperatures and flows when compared to control trials; GME counts were reduced by 99.7% post-oxygenator and 99.99% at the arterial cannula. CONCLUSION: Correlation between the use of hypobaric oxygenation and GME counts suggests hypobaric oxygenation could play a significant role in the reduction of GME. PMID- 26993482 TI - Genome-wide identification and characterization of aquaporin gene family in moso bamboo (Phyllostachys edulis). AB - Aquaporins (AQPs) are known to play a major role in maintaining water and hydraulic conductivity balance in the plant system. Numerous studies have showed AQPs execute multi-function throughout plant growth and development, including water transport, nitrogen, carbon, and micronutrient acquisition etc. However, little information on AQPs is known in bamboo. In this study, we present the first genome-wide identification and characterization of AQP genes in moso bamboo (Phyllostachys edulis) using bioinformatics. In total, 26 AQP genes were identified by homologous analysis, which were divided into four groups (PIPs, TIPs, NIPs, and SIPs) based on the phylogenetic analysis. All the genes were located on 26 different scaffolds respectively on basis of the gene mapped to bamboo genome. Evolutionary analysis indicated that Ph. edulis was more close to Oryza sativa than Zea mays in the genetic relationship. Besides, qRT-PCR was used to analyze gene expression profiles, which revealed that AQP genes were expressed constitutively in all the detected tissues, and were all responsive to the environmental cues such as drought, water, and NaCl stresses. This data suggested that AQPs may play fundamental roles in maintaining normal growth and development of bamboo, which would contribute to better understanding for the complex regulation mechanism involved in the fast-growing process of bamboo. Furthermore, the result could provide valuable information for further research on bamboo functional genomics. PMID- 26993483 TI - Perceived involvement and preferences in shared decision-making among patients with hypertension. AB - BACKGROUND: Shared decision-making (SDM) is an important component of patient centred care. However, there is limited information on its implementation in Malaysia, particularly in chronic diseases such as hypertension. OBJECTIVE: The objective of this study was to examine perceived involvement and role preferences of patients with hypertension in treatment decision-making. METHODS: A cross sectional survey was conducted among 210 patients with hypertension in a teaching hospital in Malaysia. RESULTS: The majority of respondents agreed that their doctor recognized that a decision needs to be made (89.5%) and informed them that different options are available (77.1%). However, respondents' perceived level of involvement in other aspects of treatment decision-making process was low, including in the selection of treatment and in reaching an agreement with their doctor on how to proceed with treatment. In terms of preferred decision-making roles, 51.4% of respondents preferred a collaborative role with their physicians, 44.8% preferred a passive role while only 1.9% preferred an active role. Age and educational level were found to be significantly related to patient preferences for involvement in SDM. Younger patients (<60 years) and those with higher educational level preferred SDM over passive decision-making (rho < 0.01). Encouragement from health care providers was perceived as a major motivating factor for SDM among patients with hypertension, with 91% of respondents agreeing that this would motivate their participation in SDM. CONCLUSION: Preferences for involvement in decision-making among patients with hypertension are varied, and influenced by age and educational level. Physicians have a key role in encouraging patients to participate in SDM. PMID- 26993484 TI - Antibiotic prescribing for sore throat: a cross-sectional analysis of the ReCEnT study exploring the habits of early-career doctors in family practice. AB - BACKGROUND: Acute sore throat is a common condition presenting to family practitioners. It is usually self-limiting, with antibiotic treatment recommended only for high-risk presentations. Overprescribing of antibiotics contributes to individual and community resistance. Learning to prescribe in the context of diagnostic uncertainty and patient pressures is a challenge for early-career doctors. Prescribing habits develop early and tend not to change with time. OBJECTIVE: To establish the prevalence and associations of antibiotic prescribing for acute sore throat by Australian vocational trainees in family practice. METHOD: A cross-sectional analysis of data from the Registrar Clinical Encounters in Training (ReCEnT) study. This ongoing, multicentre prospective cohort study documents the nature of trainees' consultation-based clinical experiences. Univariate and logistic regression analyses were conducted on data recorded in consultations for sore throat in nine collection periods during 2010-14. RESULTS: Data from 856 individual trainees (response rate 95.2%) were analysed. Sore throat was managed in 2.3% encounters. Antibiotics were prescribed for 71.5% of sore throat diagnoses. The variables associated with prescribing were inner regional location and higher socio-economic area. There was no significant association with younger age of patient or greater trainee experience. If an antibiotic was prescribed, the trainee was more likely to seek information from guidelines or a supervisor. CONCLUSIONS: The high frequency of antibiotic prescribing and the lack of attenuation in prescribing with increased experience suggest current educational interventions and the apprenticeship model of training is not fostering appropriate practice in this important clinical area. Targeted educational interventions, for supervisors as well as trainees, are indicated. PMID- 26993485 TI - QTLs for uniform grain dimensions and germination selected during wheat domestication are co-located on chromosome 4B. AB - KEY MESSAGE: A major locus on the long arm of wheat chromosome 4B controls within spikelet variation in both grain size and seed dormancy, the latter an important survival mechanism likely eliminated from wild wheat during domestication. Seed dormancy can increase the probability of survival of at least some progeny under unstable environmental conditions. In wild emmer wheat, only one of the two grains in a spikelet germinates during the first rainy season following maturation; and this within-plant variation in seed dormancy is associated with both grain dimension differences and position within the spikelet. Here, in addition to characterizing these associations, we elucidate the genetic mechanism controlling differential grain dimensions and dormancy within wild tetraploid wheat spikelets using phenotypic data from a wild emmer * durum wheat population and a high-density genetic map. We show that in wild emmer, the lower grain within the spikelet is about 30 % smaller and more dormant than the larger, upper grain that germinates usually within 3 days. We identify a major locus on the long arm of chromosome 4B that explains >40 % of the observed variation in grain dimensions and seed dormancy within spikelets. This locus, designated QGD-4BL, is validated using an independent set of wild emmer * durum wheat genetic stocks. The domesticated variant of this novel locus on chromosome 4B, likely fixed during the process of wheat domestication, favors spikelets with seeds of uniform size and synchronous germination. The identification of locus QGD-4BL enhances our knowledge of the genetic basis of the domestication syndrome of one of our most important crops. PMID- 26993486 TI - Quantitative trait loci controlling leaf appearance and curd initiation of cauliflower in relation to temperature. AB - KEY MESSAGE: QTL regions on chromosomes C06 and C09 are involved in temperature dependent time to curd induction in cauliflower. Temperature is the main environmental factor influencing curding time of cauliflower (Brassica oleracea var. botrytis). Temperatures above 20-22 degrees C inhibit development towards curding even in many summer cultivars. To identify quantitative trait loci (QTL) controlling curding time and its related traits in a wide range of different temperature regimes from 12 to 27 degrees C, a doubled haploid (DH) mapping population segregating for curding time was developed and days to curd initiation (DCI), leaf appearance rate (LAR), and final leaf number (FLN) were measured. The population was genotyped with 176 single nucleotide polymorphism (SNP) markers. Composite interval mapping (CIM) revealed repeatedly detected QTL for DCI on C06 and C09. The estimated additive effect increased at high temperatures. Significant QTL * environment interactions (Q * E) for FLN and DCI on C06 and C09 suggest that these hotspot regions have major influences on temperature mediated curd induction. 25 % of the DH lines did not induce curds at temperatures higher than 22 degrees C. Applying a binary model revealed a QTL with LOD >15 on C06. Nearly all lines carrying the allele of the reliable early maturing parental line (PL) on that locus induced curds at high temperatures while only half of the DH lines carrying the allele of the unreliable PL reached the generative phase during the experiment. Large variation in LAR was observed. QTL for LAR were detected repeatedly in several environments on C01, C04 and C06. Negative correlations between LAR and DCI and QTL co-localizations on C04 and C06 suggest that LAR has also effects on development towards curd induction. PMID- 26993487 TI - Does the Environment Have an Enduring Effect on ADHD? A Longitudinal Study of Monozygotic Twin Differences in Children. AB - Environmental factors play a key role in the development of Attention Deficit/Hyperactivity Disorder (ADHD), but the long-term effects of these factors are still unclear. This study analyses data from 1024 monozygotic (identical) twins in Australia, the United States, and Scandinavia who were assessed for ADHD in Preschool, Kindergarten, Grade 1, and Grade 2. Differences within each twin pair were used as a direct measure of non-shared environmental effects. The Trait State-Occasion (TSO) model developed by Cole et al. (Psychological Methods, 10, 3 20, 2005) was used to separate the non-shared environmental effects into stable factors, and transient factors that excluded measurement error. Stable factors explained, on average, 44 % and 39 % of the environmental variance in hyperactive impulsive and inattentive symptoms, respectively. Transient effects explained the remaining 56 % and 60 % of variance. The proportion of stable variance was higher than expected based on previous research, suggesting promise for targeted interventions if future research identifies these stable risk factors. PMID- 26993489 TI - Tong Luo Jiu Nao, a Chinese Medicine Formula, Reduces Inflammatory Stress in a Mouse Model of Alzheimer's Disease. AB - AIM: The aim of this study is to extend the molecular mechanism of Tong Luo Jiu Nao (TLJN) for Alzheimer's disease (AD), which is a modern Chinese formula that has been used to treat AD. METHODS: The senescence-accelerated mouse prone 8 strain (SAMP8) is one of the most appropriate models to study the mechanism that underlies AD. The levels of plasma amyloid beta (Abeta) and the Abeta deposits were measured using enzyme-linked immunosorbent assay and immunohistochemistry. Immunoblotting was used to observe the effect of TLJN on inflammatory mediator expression in an senescence-accelerated mouse model of AD. RESULTS: Our data showed that the TLJN-treated groups exhibited a reduction in plasma Abeta levels and reduced Abeta expression. Moreover, TLJN effectively attenuated Abeta-induced activation of extracellular signal-regulated kinase and c-Jun N-terminal kinases and blocked changes in inflammatory mediator expression. CONCLUSION: These data suggest that TLJN might have protective effects and could potentially act to attenuate inflammatory stress in the pathogenesis of AD. PMID- 26993490 TI - Clinical guide SEOM: hepatocellular carcinoma (HCC): considerations on SBRT. PMID- 26993488 TI - Endocytosis in enterocytes. AB - Endocytosis is a fundamental cell biological process, which carries out essential functions in a polarized epithelial cell such as enterocytes provided with a huge surface area of the brush border membrane. Major tasks of enterocytes, which are regulated by endocytic signals, are digestion and absorption of nutrients and drugs/pharmacological agents, barrier permeability to microorganism, toxins and antigens, and transcytotic crosstalk between intestinal lumen and lamina propria cells with access to the circulation.Investigations on inflammatory bowel diseases such as food allergy, celiac disease, Crohn's disease, and ulcerative colitis focus on immune processes originating within enterocytes as antigen presenting cells. Thus the initiation of oral tolerance, that is, the binding of food antigens to MHC class II proteins, might be localized within late endosomes of enterocytes. Furthermore, the late endosomal compartment of enterocytes seems to be involved in the processing of luminal antigens during the pathogenesis of celiac disease and inflammatory bowel diseases. Investigations of inherited diseases such as microvillus inclusion disease have revealed a pathogenetic defect in the autophagocytotic and/or recycling pathway of enterocytes.Our progress in the cell and molecular biological understanding of the endocytosis and the methodical opportunities of translational research offer now new therapeutic options for patients suffering from endocytosis-related diseases of enterocytes. PMID- 26993491 TI - Mu rhythm suppression demonstrates action representation in pianists during passive listening of piano melodies. AB - Musicians undergo extensive training which enhances established neural links between auditory and motor areas of the brain. Long-term training develops, strengthens and enables flexibility in these connections allowing proficiency in performance. Previous research has indicated that passive listening of trained music results in the recruitment of premotor areas. It has been argued that this sound-action representation may rely on activity in mirror neuron systems and that these systems are heavily dependent on actual sensorimotor experience. Action observation studies using electroencephalography have associated changes in mu rhythm activity with the mirror neuron system in the visuomotor domain. We aimed to investigate similar effects in the audiomotor domain. We utilised a mu suppression method in our action-listening study to detect involuntary motor coactivation when pianists passively listened to piano melodies. Wavelet analysis revealed sensorimotor mu rhythm suppression while pianists listened passively to piano melodies. Thus, we show that this spectral analysis method can also be used to demonstrate that auditory stimuli can activate the human mirror neuron system when sounds are linked to actions. Mu suppression could be a useful index for further research on action representation and training-induced plasticity. PMID- 26993492 TI - Event-related lateralized readiness potential correlates of the emotion-priming Simon effect. AB - The Simon effect indicates that the reaction time (RT) is shorter when the stimulus and response locations are congruent than when they are not. This study used a priming-target paradigm to explore the emotion-priming Simon effect with event-related potential techniques. The technique of residue iteration decomposition was employed to analyze the lateralized readiness potential (LRP) component, which contributed to disentangling the overlap between LRP and N2 central contralateral in the Simon task with horizontal stimulus-response arrangements. The behavioral result revealed significant Simon effect in RT. In the neural process, the Simon effect was reflected by both the stimulus-locked LRP (S-LRP) and the response-locked LRP (R-LRP), with the incongruent condition showing longer onset latency, larger Gratton-dip, and smaller negative-going deflection of S-LRP and smaller negative-going deflection of R-LRP. These findings suggest that the interference of irrelevant location information is located at the perceptual-encoding (indicated by S-LRP) and response-execution stages (indicated by R-LRP), providing evidence for both the perceptual interference and response-interference accounts. However, the further linear regression result signaled that the Simon effect might be more closely related to the response-execution stage than the perceptual-encoding stage. In addition, the influence of emotion on the Simon effect was salient only in the incongruent condition, showing longer onset latency of S-LRP and larger Gratton-dip of R-LRP in the negative emotion-priming condition than in the neutral emotion-priming condition, which revealed that the emotional interference effect arose from the stages of perceptual encoding and early response execution only when the locations of a stimulus and the corresponding response were incongruent. PMID- 26993493 TI - Arrhythmogenic ventricular cardiomyopathy and sudden cardiac death: Left or right? AB - Arrhythmogenic right ventricular cardiomyopathy is a leading cause of sudden cardiac death among athletes in Italy and the Mediterranean region. Although it often involves the right ventricle causing scarring, dilation, systolic impairment with aneurysm formation, it can also involve the left ventricle or present as isolated left ventricular cardiomyopathy. Cardiac magnetic resonance imaging is considered the gold standard in confirming the diagnosis. We summarize four cases of arrhythmogenic ventricular cardiomyopathy with different presentations observed over the past 2 years. PMID- 26993494 TI - Evaluation of a low-carbohydrate diet-based preparation protocol without fasting for cardiac PET/MR imaging. AB - OBJECTIVE: Assessment of increased glucose uptake in inflammatory or malignant myocardial disease using PET/MRI relies on uptake suppression in normal myocardium. We evaluated the efficacy of a >=24 hours high-fat, low-carbohydrate, and protein-permitted diet (HFLCPP) in combination with unfractionated heparin for suppression of "physiologic" myocardial glucose uptake. METHODS: PET/MRI was successfully performed in 89 patients. HFLCPP was started >=24 hours prior to PET/MRI. All patients received i.v. injection of unfractionated heparin (50 IU.kg 1) 15 minutes prior to FDG administration. Left ventricular FDG uptake was visually evaluated by two readers. Diffuse myocardial uptake exceeding liver uptake, isolated uptake in the lateral wall, or diffuse uptake in the entire circumference of the heart base were defined as failed suppression. Homogeneous myocardial uptake below liver uptake with/without focal uptake was defined as successful suppression. RESULTS: Success rate was 84%. Suppression was unsuccessful in 14 patients. No significant influence of gender (P = .40) or age (P = .21) was found. However, insufficient suppression was more common in patients younger than 45 years (20% vs 7%). PET/MR imaging completion rate was >97%. CONCLUSION: A HFLCPP diet in combination with unfractionated heparin was successfully implemented for cardiac PET/MRI and resulted in a sufficient suppression of myocardial FDG uptake in 84% of patients. PMID- 26993495 TI - Effects of dipeptidyl peptidase-4 inhibitors on cardiac and endothelial function in type 2 diabetes mellitus: A pilot study. AB - AIMS: Recent studies have raised concerns regarding increased heart failure in patients on dipeptidyl peptidase-4 inhibitors. We examined whether dipeptidyl peptidase-4 inhibitors, compared to non-incretin-based therapies, have differential effects on left ventricular and endothelial function in patients with type 2 diabetes mellitus. METHODS: A total of 25 type 2 diabetes mellitus patients commenced on a dipeptidyl peptidase-4 inhibitor were compared with 50 matched controls. Left ventricular systolic and diastolic function and flow mediated dilatation were compared before and 12 months after treatment. RESULTS: At baseline, both dipeptidyl peptidase-4 inhibitor and control groups had elevated HbA1c and comparable subclinical left ventricular dysfunction (left ventricular global longitudinal strain: -15.4% vs -15.9%, p = 0.538; e' velocities: 6 vs 6 cm/s, p = 0.151, where e' is the peak mitral annular early diastolic tissue velocity). After 12 months, both groups had similar improvement in HbA1c. However, patients on dipeptidyl peptidase-4 inhibitors had greater improvement in systolic (DeltaGLS: 3.6% vs 1.3%, p < 0.001), despite no significant differences in weight, blood pressure or lipid parameters in both groups. Diastolic (Deltae': 38% vs 17%, p = 0.001) and endothelial function improved in the dipeptidyl peptidase-4 inhibitor group but not the control group (DeltaFMD: 5% vs -1%, p = 0.029). CONCLUSION: We demonstrated significant improvements in LV systolic, diastolic and endothelial function in patients treated with a dipeptidyl peptidase-4 inhibitor over 12 months. These beneficial effects may provide some reassurance regarding the cardiovascular safety of dipeptidyl peptidase-4 inhibitors. PMID- 26993497 TI - Diabetes mellitus and coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries. AB - BACKGROUND AND AIM: Coronary flow reserve is impaired in asymptomatic patients with aortic stenosis and has a prognostic value. We investigated whether the type II diabetes mellitus additionally impairs microvascular circulation assessed by coronary flow reserve in patients with asymptomatic severe aortic stenosis, normal left ventricular ejection fraction and nonobstructed coronary arteries. METHODS: A total of 128 patients, mean age of 66.35 +/- 10.51 (58.6% males), with severe aortic stenosis and normal left ventricular ejection fraction were enrolled in this study. Patients with diabetes mellitus, those who were treated for diabetes mellitus or had documentation confirming the diagnosis of diabetes mellitus, were considered. All patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis >50% in diameter), standard transthoracic Doppler-echocardiographic study and adenosine stress transthoracic echocardiography for coronary flow reserve measurement. RESULTS: Diabetes mellitus was present in 26 patients (20.31%). There was no significant difference in aortic stenosis severity between diabetic and non-diabetic patients [aortic valve area (0.81 +/- 0.18 vs 0.85 +/- 0.15 cm(2)) and Vmax (4.20 +/- 0.57 vs 4.21 +/- 0.48 m/s)]. Mean coronary flow reserve in diabetic patients was 1.98 +/- 0.48, while mean coronary flow reserve in non-diabetic patients was 2.64 +/- 0.54 (p < 0.01). Diabetes mellitus was independent predictor of coronary flow reserve [B = -0.636, 95% confidence interval (-0.916 to -0.368), p < 0.001]. CONCLUSION: Diabetes mellitus additionally impairs coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries. PMID- 26993496 TI - (-)-Epicatechin-induced recovery of mitochondria from simulated diabetes: Potential role of endothelial nitric oxide synthase. AB - (-)-Epicatechin increases indicators associated with mitochondrial biogenesis in endothelial cells and myocardium. We investigated endothelial nitric oxide synthase involvement on (-)-epicatechin-induced increases in indicators associated with mitochondrial biogenesis in human coronary artery endothelial cells cultured in normal-glucose and high-glucose media, as well as to restore indicators of cardiac mitochondria from the effects of simulated diabetes. Here, we demonstrate the role of endothelial nitric oxide synthase on (-)-epicatechin induced increases in mitochondrial proteins, transcription factors and sirtuin 1 under normal-glucose conditions. In simulated diabetes endothelial nitric oxide synthase function, mitochondrial function-associated and biogenesis-associated indicators were adversely impacted by high glucose, effects that were reverted by (-)-epicatechin. As an animal model of type 2 diabetes, 2-month old C57BL/6 mice were fed a high-fat diet for 16 weeks. Fasting and fed blood glucose levels were increased and NO plasma levels decreased. High-fat-diet-fed mice myocardium revealed endothelial nitric oxide synthase dysfunction, reduced mitochondrial activity and markers of mitochondrial biogenesis. The administration of 1 mg/kg ( )-epicatechin for 15 days by oral gavage shifted these endpoints towards control mice values. Results suggest that endothelial nitric oxide synthase mediates (-) epicatechin-induced increases of indicators associated with mitochondrial biogenesis in endothelial cells. (-)-Epicatechin also counteracts the negative effects that high glucose or simulated type 2 diabetes has on endothelial nitric oxide synthase function. PMID- 26993498 TI - Global Cardiovascular Risk Assessment: Strengths and Limitations. AB - Global cardiovascular (CV) risk assessment tries to answer the questions: who will benefit from intervention? And when should non-pharmacologic and pharmacologic treatment be started? Used for the assessment of CV risk in the presence of one main CV risk factor, the presence of previous CV disease, diabetes, chronic kidney disease, coronary heart disease and severely elevated single risk factors, are situations with a high or very high risk. For the majority of subjects without any of the above, a calculation of risk can help to decide the best management. The methodology of assessing global CV risk has both strength and limitations. Several computational methods have been developed to assess global CV risk but no risk estimation can consider all the potential risk factors. The most used score chart is the Framingham CardioVascular Risk Score, although in Europe the Systematic Coronary risk evaluation is widespread. The strengths of the global CV risk scores depend on the methodology applied at the time of construction: (a) appropriate statistical methods (representative sample, sufficient power, clear definition of the outcomes); (b) inclusion of appropriate risk factors (age, sex, conventional risk factors, and inclusion of others that can be relevant). Once developed, the function requires internal and external validity as well as calibration. There are several limitations, which have been solved with different approaches. In the case of hypertension, one element is introduced in the score charts, the presence of hypertension-induced organ damage offering a refinement of the approach to the global CV risk. PMID- 26993499 TI - Oropharyngeal squamous cell carcinomas differentially express granzyme inhibitors. AB - OBJECTIVES: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have an improved prognosis compared to HPV negative OPSCCs. Several theories have been proposed to explain this relatively good prognosis. One hypothesis is a difference in immune response. In this study, we compared tumor-infiltrating CD3+, CD4+, CD8+ T-cells, and granzyme inhibitors (SERPINB1, SERPINB4, and SERPINB9) between HPV-positive and HPV-negative tumors and the relation with survival. METHODS: Protein expression of tumor-infiltrating lymphocytes (TILs) (CD3, CD4, and CD8) and granzyme inhibitors was analyzed in 262 OPSCCs by immunohistochemistry (IHC). Most patients (67%) received primary radiotherapy with or without chemotherapy. Cox regression analysis was carried out to compare overall survival (OS) of patients with low and high TIL infiltration and expression of granzyme inhibitors. RESULTS: HPV-positive OPSCCs were significantly more heavily infiltrated by TILs (p < 0.001) compared to HPV negative OPSCCs. A high level of CD3+ TILs was correlated with a favorable outcome in the total cohort and in HPV-positive OPSCCs, while it reached no significance in HPV-negative OPSCCs. There was expression of all three granzyme inhibitors in OPSCCs. No differences in expression were found between HPV positive and HPV-negative OPSCCs. Within the group of HPV-positive tumors, a high expression of SERPINB1 was associated with a significantly worse overall survival. CONCLUSION: HPV-positive OPSCCs with a low count of CD3+ TILs or high expression of SERPINB1 have a worse OS, comparable with HPV-negative OPSCCs. This suggests that the immune system plays an important role in the carcinogenesis of the virally induced oropharynx tumors. PMID- 26993501 TI - The impact of ethical climate types on nurses' behaviors in Bosnia and Herzegovina. AB - BACKGROUND: The performance of nurses has become vital in hospitals. Some studies have suggested that nurses' perceptions of the ethical climate in their hospitals are related to higher job satisfaction and organizational commitment and in turn lessen the issue of nursing shortage. HYPOTHESIS: (1) The ethical climate types "caring," "independent," "law and code," and "rules" have a significant positive impact on overall job satisfaction. (2) The ethical climate types and overall job satisfaction have significant positive influences on normative and affective and significant negative influences on continuance commitment. RESEARCH DESIGN: The study uses path analysis to understand which types of ethical climate impact overall job satisfaction. It also tries to find the effect of different types of ethical climate and overall job satisfaction on the components of organizational commitment. The relationships between variables were evaluated using factor analysis, reliability, descriptive statistics, correlations, and regression in this study. Participants and research context: A total of 171 useful questionnaires were collected from nurses working in public and private hospitals in Bosnia and Herzegovina. Ethical considerations: Formal research approval was obtained from the administration of each study hospital. Questionnaires with a cover letter were mailed to the hospitals that agreed to participate in the study. In the cover letter, the researchers explained the study purpose, encouraged nurses' voluntary participation, and guaranteed the anonymity of participants. FINDINGS: In the first path analyses, "rules" and "caring" climates significantly and positively affected overall job satisfaction. In the second one, while overall job satisfaction and "rules" climate significantly influenced normative commitment, "caring" climate and overall job satisfaction significantly affected affective commitment. DISCUSSION: The findings of the study have been convenient with the literature. CONCLUSION: Public and private hospitals can enhance overall job satisfaction and organizational commitment by altering the ethical climate of organizations. Hospital administrations should nurture caring and rule types of ethical climate which influence overall satisfaction. By this way, they could reduce nursing shortage. PMID- 26993500 TI - Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression. AB - Genome-wide association studies (GWAS) have identified a large number of disease associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for transcription factors binding preferentially to one allele. We found 9962 candidate regulatory SNPs, of which 16 % were rare and showed evidence of larger functional effect than common ones. Functionally rare variants may explain divergent GWAS results between populations and are candidates for a partial explanation of the missing heritability. The majority of allele-specific variants (96 %) were specific to a cell type. Furthermore, by examining GWAS loci we found >400 allele-specific candidate SNPs, 141 of which were highly relevant in our cell types. Functionally validated SNPs support identification of an SNP in SYNGR1 which may expose to the risk of rheumatoid arthritis and primary biliary cirrhosis, as well as an SNP in the last intron of COG6 exposing to the risk of psoriasis. We propose that by repeating the ChIP-seq experiments of 20 selected transcription factors in three to ten people, the most common polymorphisms can be interrogated for allele-specific binding. Our strategy may help to remove the current bottleneck in functional annotation of the genome. PMID- 26993502 TI - Schwann Cell Exosomes Mediate Neuron-Glia Communication and Enhance Axonal Regeneration. AB - The functional and structural integrity of the nervous system depends on the coordinated action of neurons and glial cells. Phenomena like synaptic activity, conduction of action potentials, and neuronal growth and regeneration, to name a few, are fine tuned by glial cells. Furthermore, the active role of glial cells in the regulation of neuronal functions is underscored by several conditions in which specific mutation affecting the glia results in axonal dysfunction. We have shown that Schwann cells (SCs), the peripheral nervous system glia, supply axons with ribosomes, and since proteins underlie cellular programs or functions, this dependence of axons from glial cells provides a new and unexplored dimension to our understanding of the nervous system. Recent evidence has now established a new modality of intercellular communication through extracellular vesicles. We have already shown that SC-derived extracellular vesicles known as exosomes enhance axonal regeneration, and increase neuronal survival after pro degenerative stimuli. Therefore, the biology nervous system will have to be reformulated to include that the phenotype of a nerve cell results from the contribution of two nuclei, with enormous significance for the understanding of the nervous system in health and disease. PMID- 26993503 TI - alpha-Synuclein in Extracellular Vesicles: Functional Implications and Diagnostic Opportunities. AB - Fibrillar inclusions of intraneuronal alpha-synuclein can be detected in certain brain areas from patients with Parkinson's disease (PD) and other disorders with Lewy body pathology. These insoluble protein aggregates do not themselves appear to have a prominent neurotoxic effect, whereas various alpha-synuclein oligomers appear harmful. Although it is incompletely known how the prefibrillar species may be pathogenic, they have been detected both within and on the outside of exosomes and other extracellular vesicles (EVs), suggesting that such structures may mediate toxic alpha-synuclein propagation between neurons. Vesicular transfer of alpha-synuclein may thereby contribute to the hierarchical spreading of pathology seen in the PD brain. Although the regulation of alpha-synuclein release via EVs is not understood, data suggest that it may involve other PD related molecules, such as LRRK2 and ATP13A2. Moreover, new evidence indicates that CNS-derived EVs in plasma have the potential to serve as biomarkers for diagnostic purposes. In a recent study, levels of alpha-synuclein were found to be increased in L1CAM-positive vesicles isolated from plasma of PD patients compared to healthy controls, and follow-up studies will reveal whether alpha synuclein in EVs could be developed as a future disease biomarker. Preferentially, toxic prefibrillar alpha-synuclein oligomers should then be targeted as a biomarker-as evidence suggests that they reflect the disease process more closely than total alpha-synuclein content. In such studies, it will be essential to adopt stringent EV isolation protocols in order to avoid contamination from the abundant pool of free plasma alpha-synuclein in different aggregational states. PMID- 26993505 TI - Neurovesicles in Brain Development. AB - Long before the nervous system is organized into electrically active neural circuits, connectivity emerges between cells of the developing brain through extracellular signals. Extracellular vesicles that shuttle RNA, proteins, and lipids from donor cells to recipient cells are candidates for mediating connectivity in the brain. Despite the abundance of extracellular vesicles during brain development, evidence for their physiological functions is only beginning to materialize. Here, we review evidence of the existence, content, and functions of extracellular vesicles in brain development. PMID- 26993507 TI - Matrix Metalloproteinase-Mediated Neuroinflammation in Vascular Cognitive Impairment of the Binswanger Type. AB - Vascular cognitive impairment (VCI) is a heterogeneous group of diseases linked together by cerebrovascular disease. Treatment of VCI has been hindered by the lack of a coherent pathophysiological process that could provide molecular targets. Of the several forms of VCI, the small vessel disease form is both the most prevalent and generally has a progressive course. Binswanger's disease (BD) is the small vessel form of VCI that involves extensive injury to the deep white matter. Growing evidence suggests that there is disruption of the blood-brain barrier (BBB) secondary to an inflammatory state. Matrix metalloproteinases (MMPs) are increased in the brain and CSF of patients with BD, and have been shown to disrupt the BBB in animal studies, suggesting that they may be biomarkers and therapeutic targets. Multimodal biomarkers derived from clinical, neuropsychological, imaging, and biochemical data can be used to narrow the VCI population to the progressive inflammatory form that will be optimal for treatment trials. This review describes the role of the MMPs in pathophysiology and their use as biomarkers. PMID- 26993506 TI - Neurovascular and Cognitive failure in Alzheimer's Disease: Benefits of Cardiovascular Therapy. AB - Alzheimer's disease (AD) is a multifactorial and multifaceted disease for which we currently have very little to offer since there is no curative therapy, with only limited disease-modifying drugs. Recent studies in AD mouse models that recapitulate the amyloid-beta (Abeta) pathology converge to demonstrate that it is possible to salvage cerebrovascular function with a variety of drugs and, particularly, therapies used to treat cardiovascular diseases such as hypercholesterolemia and hypertension. These drugs can reestablish dilatory function mediated by various endothelial and smooth muscle ion channels as well as nitric oxide availability, benefits that result in normalized brain perfusion. These cerebrovascular benefits would favor brain perfusion, which may help maintain neuronal function and, possibly, delay cognitive failure. However, restoring cerebrovascular function in AD mouse models was not necessarily accompanied by rescue of cognitive deficits related to spatial learning and memory. The results with cardiovascular therapies rather suggest that drugs originally designed to treat cardiovascular diseases that concurrently restore cerebrovascular and cognitive function do so through their pleiotropic effects. Specifically, recent findings suggest that these drugs act directly on brain cells and neuronal pathways involved in memory formation, hence, working simultaneously albeit independently on neuronal and vascular targets. These findings may help select medications for patients with cardiovascular diseases at risk of developing AD with increasing age. Further, they may identify molecular targets for recovering memory pathways that bear potential for new therapeutic avenues. PMID- 26993508 TI - Environmental Enrichment Stimulates Immune Cell Secretion of Exosomes that Promote CNS Myelination and May Regulate Inflammation. AB - Environmental enrichment (EE) consists of increased physical, intellectual, and social activity, and has wide-ranging effects, including enhancing cognition, learning and memory, and motor coordination. Animal studies have demonstrated that EE improves outcome of brain trauma and neurodegenerative disorders, including demyelinating diseases like multiple sclerosis, making it a promising therapeutic option. However, the complexity of applying a robust EE paradigm makes clinical use difficult. A better understanding of the signaling involved in EE-based neuroprotection may allow for development of effective mimetics as an alternative. In prior work, we found that exosomes isolated from the serum of rats exposed to EE impact CNS myelination. Exosomes are naturally occurring nanovesicles containing mRNA, miRNA, and protein, which play important roles in cell function, disease, and immunomodulation. When applied to hippocampal slice cultures or nasally administered to naive rats, EE-serum exosomes significantly increase myelin content, oligodendrocyte precursor (OPC) and neural stem cell levels, and reduce oxidative stress (OS). We found that rat EE exosomes were enriched in miR-219, which is necessary and sufficient for OPC differentiation into myelinating cells. Thus, peripherally produced exosomes may be a useful therapy for remyelination. Here, we aim to better characterize the impact of EE on CNS health and to determine the cellular source of nutritive exosomes found in serum. We found that exosomes isolated from various circulating immune cell types all increased slice culture myelin content, contained miR-219, and reduced OS, suggesting that EE globally alters immune function in a way that supports brain health. PMID- 26993504 TI - Extracellular Vesicles in Brain Tumor Progression. AB - Brain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs). EVs serve as unique carriers of bioactive lipids, secretable and non-secretable proteins, mRNA, non-coding RNA, and DNA and constitute pathway(s) of extracellular exit of molecules into the intercellular space, biofluids, and blood. EVs are also highly heterogeneous as reflected in their nomenclature (exosomes, microvesicles, microparticles) attempting to capture their diverse origin, as well as structural, molecular, and functional properties. While EVs may act as a mechanism of molecular expulsion, their non random uptake by heterologous cellular recipients defines their unique roles in the intercellular communication, horizontal molecular transfer, and biological activity. In the central nervous system, EVs have been implicated as mediators of homeostasis and repair, while in cancer they may act as regulators of cell growth, clonogenicity, angiogenesis, thrombosis, and reciprocal tumor-stromal interactions. EVs produced by specific brain tumor cell types may contain the corresponding oncogenic drivers, such as epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (and hence are often referred to as 'oncosomes'). Through this mechanism, mutant oncoproteins and nucleic acids may be transferred horizontally between cellular populations altering their individual and collective phenotypes. Oncogenic pathways also impact the emission rates, types, cargo, and biogenesis of EVs, as reflected by preliminary analyses pointing to differences in profiles of EV-regulating genes (vesiculome) between molecular subtypes of glioblastoma, and in other brain tumors. Molecular regulators of vesiculation can also act as oncogenes. These intimate connections suggest the context-specific roles of different EV subsets in the progression of specific brain tumors. Advanced efforts are underway to capture these events through the use of EVs circulating in biofluids as biomarker reservoirs and to guide diagnostic and therapeutic decisions. PMID- 26993510 TI - pERK1/2 Peripheral Recruitment and Filopodia Protrusion Augment Oligodendrocyte Progenitor Cell Migration: Combined Effects of PDGF-A and Fibronectin. AB - Oligodendrocyte progenitor cell (OPC) migration is critical for effective myelination of the central nervous system. Not only during normal myelination but also during remyelination, the growth factors (GFs) and extracellular matrix (ECM) protein affect the OPC migration. Studies showed the altered levels of GFs and ECM in the demyelinating lesions. In our earlier studies, we have shown that the effect of platelet-derived growth factor alpha (PDGF-A) on OPC migration is dose- and time-dependent. In that we have shown that the physiological concentration (1 ng/ml) of PDGF-A was unable to induce OPC migration at transient exposure (30 min). However, the involvement of ECM in the regulation of PDGF-A mediated OPC migration was not clear. In the present study, we have used fibronectin (FN) as ECM. PDGF-A and FN have similar and overlapping intracellular signaling pathways including the extracellular regulated kinases 1 and 2 (ERK1/2). Here we demonstrate how physiological concentration of PDGF-A combines with FN to augment OPC migration in vitro. The present study is first of its kind to show the importance of the synergistic effects of PDGF-A and FN on peripheral recruitment of phosphorylated/activated ERK1/2 (pERK1/2), actin-pERK1/2 co localization, and filopodia formation, which are essential for the enhanced OPC migration. These findings were further confirmed by ERK1/2 inhibition studies, using the pharmacological inhibitor U0126. An understanding of these complex interactions may lead to additional strategies for transplanting genetically modified OPCs to repair widespread demyelinated lesions. PMID- 26993509 TI - Leptin Dysfunction and Alzheimer's Disease: Evidence from Cellular, Animal, and Human Studies. AB - There is accumulating evidence from epidemiological studies that changes in body weight are associated with Alzheimer's disease (AD) from mid-life obesity increasing the risk of developing AD to weight loss occurring at the earliest stages of AD. Therefore, factors that regulate body weight are likely to influence the development and progression of AD. The adipocyte-derived hormone leptin has emerged as a major regulator of body weight mainly by activating hypothalamic neural circuits. Leptin also has several pleotropic effects including regulating cognitive function and having neuroprotective effects, suggesting a potential link between leptin and AD. Here, we will examine the relationship between leptin and AD by reviewing the recent evidence from cellular and animal models to human studies. We present a model where leptin has a bidirectional role in AD. Not only can alterations in leptin levels and function worsen cognitive decline and progression of AD pathology, but AD pathology, in of itself, can disrupt leptin signaling, which together would lead to a downward spiral of progressive neurodegeneration and worsening body weight and systemic metabolic deficits. Collectively, these studies serve as a framework to highlight the importance of understanding the molecular mechanisms underlying the body weight and systemic metabolic deficits in AD, which has the potential to open new avenues that may ultimately lead to novel therapeutic targets and diagnostic tools. PMID- 26993511 TI - Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases. AB - Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases. PMID- 26993512 TI - Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases. AB - The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (Abeta). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer's disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that Abeta is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of Abeta in the glia limitans in Alzheimer's disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of Abeta. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance. PMID- 26993515 TI - Two-year stability of immobilization effect of sepiolite on Cd contaminants in paddy soil. AB - The long-term stability of immobilization effect of immobilization agents was critical to the remediation practices. Two years consecutive in situ field-scale demonstration was conducted in Hunan province, with the purpose to certify the long-term stability of immobilization effect of sepiolite on Cd contaminants in paddy soil in the aspect of soil extraction and plant uptake. Natural sepiolite was selected as immobilization, and rice was the model plant. The immobilization effect of sepiolite on Cd contaminants in paddy soil was significant in the first year and remained at the second year. The Cd content of brown rice, 0.025 M HCl extractable Cd content and exchangeable Cd content of paddy soil decreased remarkably. The application of sepiolite led to an obvious increase in pH value of paddy soil and carbonate bounded fraction of Cd in soil. The immobilization effect was maintained even at the second year without any additional amendments. The results indicated the interaction of sepiolite and cadmium was a long-term process. The additional sepiolite at the second year had no significant lift effect on immobilization so that it was unnecessary to add sepiolite every year based on the immobilization effect and operation cost. The dynamics of available Cu, Zn, and Mn contents in paddy soil in two consecutive years indicated sepiolite had negligible effects on the bioavailability of trace metals. The result of the current research confirmed the stability of immobilization effect of sepiolite. PMID- 26993514 TI - ExRNA in Biofluids as Biomarkers for Brain Tumors. AB - Patients with high-grade gliomas and glioblastomas (GBMs) have poor survival despite optimal surgical and drug therapy. Minimally invasive diagnostic biomarkers would enable early diagnosis and tumor-specific treatments for 'personalized targeted' therapy, and would create the basis for response tracking in patients with GBM. Extracellular vesicles (EVs) isolated from cerebrospinal fluid and blood contain glioma-specific molecules, including tumor-derived EV RNAs that are detectable in small copy numbers in these biofluids. EV RNA mutations or expression changes are also detectable, the analysis of which gives rise to 'liquid biopsy' tumor profiling. PMID- 26993513 TI - Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer's Disease. AB - Alzheimer's disease is the most frequent type of dementia and diagnosed late in the progression of the illness when irreversible brain tissue loss has already occurred. For this reason, treatments have been ineffective. It is imperative to find novel therapies ameliorating modifiable risk factors (hypertension, stroke, diabetes, chronic kidney disease, and traumatic brain injury) and effective against early pathogenic mechanisms including alterations in cerebral blood flow leading to poor oxygenation and decreased access to nutrients, impaired glucose metabolism, chronic inflammation, and glutamate excitotoxicity. Angiotensin II receptor blockers (ARBs) fulfill these requirements. ARBs are directly neuroprotective against early injury factors in neuronal, astrocyte, microglia, and cerebrovascular endothelial cell cultures. ARBs protect cerebral blood flow and reduce injury to the blood brain barrier and neurological and cognitive loss in animal models of brain ischemia, traumatic brain injury, and Alzheimer's disease. These compounds are clinically effective against major risk factors for Alzheimer's disease: hypertension, stroke, chronic kidney disease, diabetes and metabolic syndrome, and ameliorate age-dependent cognitive loss. Controlled studies on hypertensive patients, open trials, case reports, and database meta analysis indicate significant therapeutic effects of ARBs in Alzheimer's disease. ARBs are safe compounds, widely used to treat cardiovascular and metabolic disorders in humans, and although they reduce hypertension, they do not affect blood pressure in normotensive individuals. Overall, there is sufficient evidence to consider long-term controlled clinical studies with ARBs in patients suffering from established risk factors, in patients with early cognitive loss, or in normal individuals when reliable biomarkers of Alzheimer's disease risk are identified. PMID- 26993516 TI - Reply to: Bakri balloon vs. B-Lynch suture as hemostatic procedures for atonic bleeding: clarifications and concerns. PMID- 26993517 TI - Altered FoxO3 expression and apoptosis in granulosa cells of women with polycystic ovary syndrome. AB - PURPOSE: To determine the level of apoptosis, and alteration of FoxO3 (forkhead box O3 transcription factor) expression and phosphorylation in human granulosa cells amongst polycystic ovary syndrome (PCOS) patients and control group. METHODS: We recruited infertile women with PCOS (n = 14) and compared them with infertile women due to tubal blockage or male factor infertility (n = 14, controls). GnRH agonist and gonadotropins were used for ovarian stimulation. Follicular fluids from large follicles (>16 mm) were pooled and granulosa cells (GCs) were isolated using cell strainer methodology. Apoptosis of purified GCs was measured by flow cytometry using Annexin V and propidium iodide. Quantitative real-time PCR and western blotting were performed to assess alteration of FoxO3 expression and phosphorylation in GCs. RESULTS: There were higher percentages of early and late apoptosis in GCs of PCOS patients than in the control group. FoxO3 mRNA level and total FoxO3 protein were significantly higher in PCOS group than in the control group. The ratio of p-FoxO3/total FoxO3 decreased significantly in PCOS than in the control group. It was inferred that unphosphorylated (active form) FoxO3 was higher in GCs of PCOS patients. Apoptosis was significantly and positively correlated with the total FoxO3 and negatively correlated with the p FoxO3 protein levels in PCOS patients. CONCLUSIONS: Activation and overexpression of FoxO3 in granulosa cells of PCOS women correlated with higher apoptosis levels in these cells suggesting that FoxO3 may be a candidate for the higher apoptosis in granulosa cells from women with PCOS. PMID- 26993518 TI - Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients. AB - PURPOSE: New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO). METHODS: Consecutive patients with serous OC were enrolled. These two grading systems were assessed independently from each other. Kaplan-Meier estimates and Cox-regression analyses were performed to validate and compare their prognostic impact. RESULTS: 143 consecutive patients entered the study. According to the Kaplan-Meier estimates, the MDACC grading system (p = 0.001) predicted the progression free survival (PFS) more precisely than the FIGO system (p = 0.025). The MDACC grading system (p = 0.008) but not the FIGO system (p = 0.329) showed a statistically significant difference in terms of disease specific survival (DSS). Multivariable Cox-regression analyses revealed an independent prognostic impact of the MDACC grading system but not of the FIGO system for PFS (HR 1.570; 95 % CI 1.007-2.449; p = 0.047, and HR 0.712; 95 % CI 0.476-1.066; p = 0.099, respectively). Concerning DSS, the two-tier grading system but not the FIGO system showed a prognostic impact in a univariable Cox-regression analysis (HR 2.152; 95 % CI 1.207-3.835; p = 0.009, and HR 1.258; 95 % CI 0.801-1.975; p = 0.319, respectively). CONCLUSIONS: We were able to validate the MDACC grading system in serous OC. Moreover, this grading system was stronger associated with survival than the FIGO system. PMID- 26993519 TI - Sexual Health and Positive Subjective Well-Being in Partnered Older Men and Women. AB - OBJECTIVES: We examine the associations between different patterns of sexual behavior and function and three indicators of subjective well-being (SWB) covering eudemonic, evaluative, and affective well-being in a representative sample of partnered older people. METHOD: Using data from a Sexual Relationships and Activities Questionnaire (SRA-Q) in Wave 6 of the English Longitudinal Study of Ageing, latent class analysis identified groups characterized by distinctive patterns of sexual behavior and function and then examined their link to SWB. Eudemonic SWB was measured using a revised 15-item version of the CASP-19, evaluative SWB using the Satisfaction With Life Scale, and affective SWB using the 8-item version of the Centre for Epidemiologic Studies-Depression scale. RESULTS: Sexual behavior and function was best described by six classes among men and five classes among women. These ranged from high sexual desire, frequent partnered sexual activities, and few sexual problems (Class 1) to low sexual desire, infrequent/no sexual activity, and problems with sexual function (Class 5([women])/6([men])). Men and women who reported either infrequent/no sexual activity, or were sexually active but reported sexual problems, generally had lower SWB than those individuals identified in Class 1. Poorer SWB in men was more strongly associated with sexual function difficulties, whereas in women desire and frequency of partnered activities appeared more important in relation to SWB. DISCUSSION: Within the context of a partnered relationship continuing sexual desire, activity and functioning are associated with higher SWB, with distinctive patterns for women and men. PMID- 26993520 TI - Murine models of cardiovascular comorbidity in chronic obstructive pulmonary disease. AB - Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for cardiovascular disease (CVD). Currently, COPD patients with atherosclerosis (i.e., the most important underlying cause of CVD) receive COPD therapy complemented with standard CVD therapy. This may, however, not be the most optimal treatment. To investigate the link between COPD and atherosclerosis and to develop specific therapeutic strategies for COPD patients with atherosclerosis, a substantial number of preclinical studies using murine models have been performed. In this review, we summarize the currently used murine models of COPD and atherosclerosis, both individually and combined, and discuss the relevance of these models for studying the pathogenesis and development of new treatments for COPD patients with atherosclerosis. Murine and clinical studies have provided complementary information showing a prominent role for systemic inflammation and oxidative stress in the link between COPD and atherosclerosis. These and other studies showed that murine models for COPD and atherosclerosis are useful tools and can provide important insights relevant to understanding the link between COPD and CVD. More importantly, murine studies provide good platforms for studying the potential of promising (new) therapeutic strategies for COPD patients with CVD. PMID- 26993521 TI - Biosynthesis of the polymeric gel-forming mucin MUC5B. AB - MUC5B is a major polymeric mucin in the airway mucus gel and is an essential component of innate defense of the respiratory epithelium. Knowledge of the synthesis and intracellular processing of MUC5B is incomplete. We investigated the molecular details of MUC5B assembly in primary human bronchial epithelial cells (HBECs) grown at an air-liquid interface (ALI). Electrophoretic and centrifugal separations of intracellular forms of MUC5B probed with antibodies specific for non-O-glycosylated and O-glycosylated forms of the mucin identified three major intracellular populations of MUC5B (non-O-glycosylated monomer and dimer, and O-glycosylated polymers). Biophysical analysis of recombinant MUC5B COOH-terminus (CT5B; D4-B-C-CK) expressed in 293-EBNA cells showed that MUC5B dimerizes by disulfide linkage. Pulse-chase studies in the HBEC ALI cultures showed that non-O-glycosylated MUC5B was synthesized within 20 min of metabolic labeling and O-glycosylated, polymeric mucin within 2 h. Radiolabeled O glycosylated mucin polymers were secreted within 2 h and the majority were released by 48 h. These data indicate that MUC5B follows a similar assembly to the related glycoprotein, von Willebrand factor (vWF); however, unlike vWF the MUC5B polypeptide shows no evidence of major proteolytic processing of D-domains during the production of the mature secreted polymeric mucin in normal and cystic fibrosis (CF) primary bronchial epithelial cells. In contrast, MUC5B D-domains were modified by neutrophil elastase, a protease commonly found in CF sputum, demonstrating that proteolytic degradation of MUC5B is an extracellular event in CF sputum. These results define the pathway for synthesis of MUC5B in primary human goblet cells. PMID- 26993522 TI - Systematic phenotyping and correlation of biomarkers with lung function and histology in lung fibrosis. AB - To date, phenotyping and disease course prediction in idiopathic pulmonary fibrosis (IPF) primarily relies on lung function measures. Blood biomarkers were recently proposed for diagnostic and outcome prediction in IPF, yet their correlation with lung function and histology remains unclear. Here, we comprehensively assessed biomarkers in liquid biopsies and correlated their abundance with lung function and histology during the onset, progression, and resolution of lung fibrosis, with the aim to more precisely evaluate disease progression in the preclinical model of bleomycin-induced pulmonary fibrosis in vivo. Importantly, the strongest correlation of lung function with histological extent of fibrosis was observed at day 14, whereas lung function was unchanged at days 28 and 56, even when histological assessment showed marked fibrotic lesions. Although matrix metalloproteinase-7 (MMP-7), MMP-9, and PAI-1 were significantly elevated in broncheoalveolar lavage of fibrotic mice, only soluble ICAM-1 (sICAM 1) was elevated in the peripheral blood of fibrotic mice and was strongly correlated with the extent of fibrosis. Importantly, tissue-bound ICAM-1 was also elevated in lung homogenates, with prominent staining in hyperplastic type II alveolar epithelial and endothelial cells. In summary, we show that lung function decline is not a prerequisite for histologically evident fibrosis, particularly during the onset or resolution thereof. Plasma levels of sICAM-1 strongly correlate with the extent of lung fibrosis, and may thus be considered for the assessment of intraindividual therapeutic studies in preclinical studies of pulmonary fibrosis. PMID- 26993525 TI - Yet Another Tranexamic Acid-Related Thrombotic Complication. PMID- 26993526 TI - Effects of Maintaining Body Core Temperature on Atrial Fibrillation. PMID- 26993523 TI - Chronic high-magnitude cyclic stretch stimulates EC inflammatory response via VEGF receptor 2-dependent mechanism. AB - Ventilator-induced lung injury (VILI) is associated with activated inflammatory signaling, such as cytokine production by endothelial and epithelial cells and macrophages, although the precise mechanisms of inflammatory activation induced by VILI-relevant cyclic stretch (CS) amplitude remain poorly understood. We show that exposure of human pulmonary endothelial cells (EC) to chronic CS at 18% linear distension (18% CS), but not at physiologically relevant 5% CS, induces "EC-activated phenotype," which is characterized by time-dependent increase in ICAM1 and VCAM1 expression. A preconditioning of 18% CS also increased in a time dependent fashion the release of soluble ICAM1 (sICAM1) and IL-8. Investigation of potential signaling mechanisms of CS-induced EC inflammatory activation showed that 18% CS, but not 5% CS, induced time-dependent upregulation of VEGF receptor 2 (VEGFR2), as monitored by increased protein expression and VEGFR2 tyrosine phosphorylation. Both CS-induced VEGFR2 expression and tyrosine phosphorylation were abrogated by cotreatment with reactive oxygen species inhibitor, N-acetyl cysteine. Molecular inhibition of VEGFR2 expression by gene-specific siRNA or treatment with VEGFR2 pharmacological inhibitor SU-1498 attenuated CS-induced activation of ICAM1 and VCAM1 expression and sICAM1 release. Chronic EC preconditioning at 18% CS augmented EC inflammation and barrier-disruptive response induced by proinflammatory cytokine TNF-alpha. This effect of chronic 18% CS preconditioning was attenuated by siRNA-induced VEGFR2 knockdown. This study demonstrates for the first time a VEGFR2-dependent mechanism of EC inflammatory activation induced by pathological CS. We conclude that, despite the recognized role of VEGF as a prosurvival and angiogenic factor, excessive activation of VEGFR2 signaling by high-tidal-volume lung mechanical ventilation may contribute to ventilator-induced (biotrauma) lung inflammation and barrier dysfunction by augmenting cell response to VILI-associated inflammatory mediators. PMID- 26993527 TI - Polyploidy and the proteome. AB - Although major advances have been made during the past 20 years in our understanding of the genetic and genomic consequences of polyploidy, our knowledge of polyploidy and the proteome is in its infancy. One of our goals is to stimulate additional study, particularly broad-scale proteomic analyses of polyploids and their progenitors. Although it may be too early to generalize regarding the extent to which transcriptomic data are predictive of the proteome of polyploids, it is clear that the proteome does not always reflect the transcriptome. Despite limited data, important observations on the proteomes of polyploids are emerging. In some cases, proteomic profiles show qualitatively and/or quantitatively non-additive patterns, and proteomic novelty has been observed. Allopolyploids generally combine the parental contributions, but there is evidence of parental dominance of one contributing genome in some allopolyploids. Autopolyploids are typically qualitatively identical to but quantitatively different from their parents. There is also evidence of parental legacy at the proteomic level. Proteomes clearly provide insights into the consequences of genomic merger and doubling beyond what is obtained from genomic and/or transcriptomic data. Translating proteomic changes in polyploids to differences in morphology and physiology remains the holy grail of polyploidy- this daunting task of linking genotype to proteome to phenotype should emerge as a focus of polyploidy research in the next decade. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID- 26993528 TI - CuO embedded chitosan spheres as antibacterial adsorbent for dyes. AB - Chitosan/copper oxide (CS/CuO) composite spheres were prepared by simple mixing of CuO nanomaterials in CS solution followed by dropwise addition to NH4OH solution. The characterizations of all the prepared spheres were carried out by FESEM, EDS, XRD, XPS, and FTIR analyses while the thermal properties were analyzed by TGA. Further the ability of composite spheres was tested as an easily removable pollutant adsorbent from water containing different dyes and compared with pure CS. Composite spheres were found to be the best adsorbent when applied to remove indigo carmine (IC), congo red (CR) and methyl orange (MO) from water. Amongst the three dyes, CS/CuO composite spheres were more selective toward MO adsorption. CS/CuO composite spheres also displayed significant antibacterial activity by inhibiting Pseudomonas aeruginosa growth. Thus the fabricated composite spheres can be used as a biosorbent in the future. PMID- 26993524 TI - Elevated expression of NEU1 sialidase in idiopathic pulmonary fibrosis provokes pulmonary collagen deposition, lymphocytosis, and fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) poses challenges to understanding its underlying cellular and molecular mechanisms and the development of better therapies. Previous studies suggest a pathophysiological role for neuraminidase 1 (NEU1), an enzyme that removes terminal sialic acid from glycoproteins. We observed increased NEU1 expression in epithelial and endothelial cells, as well as fibroblasts, in the lungs of patients with IPF compared with healthy control lungs. Recombinant adenovirus-mediated gene delivery of NEU1 to cultured primary human cells elicited profound changes in cellular phenotypes. Small airway epithelial cell migration was impaired in wounding assays, whereas, in pulmonary microvascular endothelial cells, NEU1 overexpression strongly impacted global gene expression, increased T cell adhesion to endothelial monolayers, and disrupted endothelial capillary-like tube formation. NEU1 overexpression in fibroblasts provoked increased levels of collagen types I and III, substantial changes in global gene expression, and accelerated degradation of matrix metalloproteinase-14. Intratracheal instillation of NEU1 encoding, but not control adenovirus, induced lymphocyte accumulation in bronchoalveolar lavage samples and lung tissues and elevations of pulmonary transforming growth factor beta and collagen. The lymphocytes were predominantly T cells, with CD8(+) cells exceeding CD4(+) cells by nearly twofold. These combined data indicate that elevated NEU1 expression alters functional activities of distinct lung cell types in vitro and recapitulates lymphocytic infiltration and collagen accumulation in vivo, consistent with mechanisms implicated in lung fibrosis. PMID- 26993530 TI - Effects of the ultra-high pressure on structure and alpha-glucosidase inhibition of polysaccharide from Astragalus. AB - A novel homogeneous polysaccharide fraction (APS) was extracted from Astragalus by hot water and purified by Sephadex G-100 and G-75 column. Its molecular weight was 693kDa. APS and APS with ultra-high pressure treatment exhibited significant inhibitory abilities on a-glucosidase, inhibition rate from high to low in order was 400MPa-APS, 300MPa-APS, 500MPa-APS and APS. The inhibition percentage of 400MPa-APS (1.5mg/mL) was 49% (max.). This suggested that the inhibitory activity of APS on a-glucosidase was improved by ultra-high pressure treatment. FT-IR, SEM, CD spectra, atomic force microscope and Congo red test analysis of APS and 400MPa-APS showed ultra-high pressure treatment didn't change the preliminary structure but had an effect on its advanced structure. PMID- 26993529 TI - Schisandra polysaccharide increased glucose consumption by up-regulating the expression of GLUT-4. AB - In our previous study, a polysaccharide was extracted from Schisandra Chinensis (Trucz.) Baill and found with anti-diabetic effects. The aim of this study was to investigate the anti-diabetic effects of the low weight molecular polysaccharide (SCPP11) purified from crude Schisandra polysaccharide and illustrate the underlying mechanism in buffalo rat liver cells. The insulin resistance model of BRL cells was established by incubating with insulin solution for 24h. The effects of SCPP11 on regulating related protein and mRNA expression in an insulin and AMPK signal pathway were investigated by western blot and RT-PCR analysis. SCPP11 showed no cytotoxicity to BRL cells and could improve the glucose consumption in BRL cells. SCPP11 increased the protein expression of Akt, p-AMPK and GLUT-4 in BRL cells. Moreover, SCPP11 could enhance the mRNA expression levels of IRS-1, PI3K, Akt, GLUT-4, AMPKalpha and PPAR-gamma in BRL cells at the same time. In conclusion, SCPP11 possessed effects in improving glucose consumption by up-regulating the expression of GLUT-4 which might occur via insulin and AMPK signal pathway and could be a potential functional food to prevent and mitigate the insulin resistance condition. PMID- 26993531 TI - Enzymatic modification of chitosan by cinnamic acids: Antibacterial activity against Ralstonia solanacearum. AB - This study aimed to identify chitosan polymers that have antibacterial activity against the bacterial wilt pathogen. The chitosan polymers were enzymatically synthesized using chitosan and five cinnamic acids (CADs): caffeic acid (CA), ferulic acid (FA), cinnamic acid (CIA), p-coumaric acid (COA) and chlorogenic acid (CHA), using laccase from Pleurotus ostreatus as a catalyst. The reaction was performed in a phosphate buffered solution under heterogenous reaction conditions. The chitosan derivatives (CTS-g-CADs) were characterized by FT-IR, XRD, TGA and SEM. FT-IR demonstrated that the reaction products bound covalently to the free amino groups or hydroxyl groups of chitosan via band of amide I or ester band. XRD showed a reduced packing density for grafted chitosan comparing to original chitosan. TGA demonstrated that CTS-g-CADs have a higher thermostability than chitosan. Additionally, chitosan and its derivatives showed similar antibacterial activity. However, the IC50 value of the chitosan-caffeic acid derivative (CTS-g-CA) against the mulberry bacterial wilt pathogen RS-5 was 0.23mg/mL, which was two-fifths of the IC50 value of chitosan. Therefore, the enzymatically synthesized chitosan polymers can be used to control plant diseases in biotechnological domains. PMID- 26993532 TI - A novel modified graphene oxide/chitosan composite used as an adsorbent for Cr(VI) in aqueous solutions. AB - A novel adsorbent for removal of hexavalent chromium (Cr(VI)) from aqueous solutions has been successfully prepared by modifying graphene oxide/chitosan composite with disodium ethylenediaminetetraacetate (EDTA-2Na) (GEC). This modified composite was characterized by various technologies; including scanning electron microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Batch adsorption experiments were carried out to evaluate the adsorption of Cr(VI) by GEC under different conditions. The results indicate that the adsorption of Cr(VI) on GEC was highly pH-dependent, with the highest adsorption capacity (86.17mg/g) occurring at pH 2. The kinetics of adsorption exhibited pseudo-second order behavior. The adsorption data were well described by the Freundlich isotherm model. The adsorption capacity increased with increasing temperature. The calculated thermodynamic parameters indicate that the adsorption is a spontaneous, endothermic and feasible process. The further regeneration experiments showed the adsorption capacity of GEC for Cr(VI) decreased 5% after 7 times reuse, indicating the potential of the as-prepared material for practical application. PMID- 26993533 TI - Brix refractometry in serum as a measure of failure of passive transfer compared to measured immunoglobulin G and total protein by refractometry in serum from dairy calves. AB - A series of trials were conducted to evaluate Brix refractometry (Brix %) for the assessment of failure of passive transfer (FPT) in dairy calves compared to: (1) serum IgG (reference standard) when measured by radial immunodiffusion (RID) or a turbidometric immunoassay (TIA), and (2) serum total protein refractometry (STP). For the serum samples tested with TIA, STP, and Brix % (n = 310; Holstein calves), the median concentrations were 21.3 g/L IgG, 58 g/L STP, and 9.2%, respectively. For the serum samples tested with RID, STP and Brix % (n = 112; Jersey calves), the mean concentrations were 38 g/L IgG, 68 g/L STP, and 10.2%, respectively. For samples tested with only Brix % and STP (n = 265; Holstein calves), median STP and Brix % were 50 g/L STP and 8.5%, respectively. Correlations between Brix % and RID, and between Brix % and TIA were equal (r = 0.79, respectively). Brix % and STP were positively correlated (r = 0.99). Brix % estimated serum IgG concentrations determined by TIA and RID (r(2) = 0.63, 0.62, respectively). When FPT was defined as serum IgG < 10 g/L, Brix % <= 8.5% showed optimal sensitivity (100%) and specificity (89.2%) to predict FPT. At the same IgG cut-point, an STP value of <= 52 g/L showed a similar sensitivity (100%) and specificity (80.4%) to predict FPT. Brix refractometry predicted successful transfer of passive immunity in dairy calves, but further evaluation as a diagnostic tool for the diagnosis of FPT is warranted. PMID- 26993534 TI - A Systematic, Multi-domain Review of Mobile Smartphone Apps for Evidence-Based Stress Management. AB - CONTEX: Chronic stress presents a growing, pervasive burden in healthcare, and mobile smartphone applications (apps) have the potential to deliver evidence based stress management strategies. This review identified and evaluated stress management apps across domains of (1) evidence-based content; (2) transparency in app development; and (3) functionality of the app interface. EVIDENCE ACQUISITION: The iOS App Store was systematically searched. Apps with descriptions indicating that they targeted the intended audience and included evidence-related terminology, at least one evidence-based stress management strategy, and behavior change components were downloaded and evaluated by two independent raters across the three domains of evidence-based content, transparency, and functionality. EVIDENCE SYNTHESIS: A total of 902 apps were identified based on 21 searches. Of these, 60 met study criteria and were downloaded and evaluated between April and June 2015. Twenty (33%) ultimately did not deliver an evidence-based strategy. Of the delivered strategies, the most common were mindfulness and meditation (73%) and diaphragmatic breathing (25%). On average, apps addressed half of the transparency criteria, and nearly all (85%) were acceptable across usability criteria. A total of 32 apps included both evidence-based content and exhibited no problems with usability or functionality; apps affiliated with a non-profit, research-engaged institution comprised 31% of these. CONCLUSIONS: This review evaluated 60 iOS apps for stress management across domains of evidence-based content, transparency, and functionality; these apps have the potential to effectively supplement medical care. Findings further indicate that a comprehensive, multi-domain approach can distinguish apps that use evidence-based strategies from those that do not. PMID- 26993535 TI - An Economic Evaluation of PulseNet: A Network for Foodborne Disease Surveillance. AB - The PulseNet surveillance system is a molecular subtyping network of public health and food regulatory agency laboratories designed to identify and facilitate investigation of foodborne illness outbreaks. This study estimates health and economic impacts associated with PulseNet. The staggered adoption of PulseNet across the states offers a natural experiment to evaluate its effectiveness, which is measured as reduction of reported illnesses due to improved information, enhanced industry accountability, and more-rapid recalls. Economic impacts attributable to PulseNet include medical costs and productivity losses averted due to reduced illness. Program costs are also reported. Better information and accountability from enhanced surveillance is associated with large reductions of reported illnesses. Data collected between 1994 and 2009 were assembled and analyzed between 2010 and 2015. Conservatively, accounting for underreporting and underdiagnosis, 266,522 illnesses from Salmonella, 9,489 illnesses from Escherichia coli (E. coli), and 56 illnesses due to Listeria monocytogenes are avoided annually. This reduces medical and productivity costs by $507 million. Additionally, direct effects from improved recalls reduce illnesses from E. coli by 2,819 and Salmonella by 16,994, leading to $37 million in costs averted. Annual costs to public health agencies are $7.3 million. The PulseNet system makes possible the identification of food safety risks by detecting widespread or non-focal outbreaks. This gives stakeholders information for informed decision making and provides a powerful incentive for industry. Furthermore, PulseNet enhances the focus of regulatory agencies and limits the impact of outbreaks. The health and economic benefits from PulseNet and the foodborne disease surveillance system are substantial. PMID- 26993536 TI - Letter from the guest-editor. PMID- 26993537 TI - The real cost of treating venous ulcers in a contemporary vascular practice. AB - BACKGROUND: Venous leg ulcers (VLUs) are a prevalent and morbid disease that consumes considerable health care resources. Estimates place the total costs for treatment of VLU at 1% of health care budgets in many industrialized countries. Unfortunately, there is little contemporary information on the total cost of treating VLU in the United States, particularly in a wound center staffed by vascular specialists. The purpose of this study was to define the actual cost of treating VLU and to identify factors influencing costs. METHODS: A cohort of 84 patients with active VLU (Clinical, Etiologic, Anatomic, and Pathologic class 6 disease) who were treated in a wound center by five vascular surgeons with a minimum follow-up of 6 months (median, 368 days; range, 336-483 days) was retrospectively studied. Actual costs (not charges) were obtained for outpatient and inpatient facility, visiting nurse services, and our physician practice group to yield true cost. The proportion of healed VLUs and time to complete healing were determined to calculate time to healing as well as ulcer-free intervals. Calculations of cost/ulcer-free days and cost to complete healing for the entire follow-up period were carried out as well as univariate analysis of factors affecting cost. RESULTS: The mean total cost of treating VLU during this follow up period was $15,732. A total of 50 patients (60%) healed their VLUs without recurrence in a mean time of 122 days (range, 6-379 days) at a cost of $10,563 (range, $430-$50,967). This translated to $86/day of treatment to heal an ulcer, resulting in a cost of $42/ulcer-free day. In comparison, the total cost was threefold higher at $33,907 (range, $390-$132,730) for the patients (n = 17; 20%) who did not heal their VLUs. Significant contributing factors included outpatient facility fees ($10,332) and visiting nurse services ($11,365) related to extended treatment of the open VLU. Patients who had a recurrence of their VLU (n = 17; 20%) during the follow-up period had a total cost of $12,760. Inpatient admission for wound-related issues increased total cost to $33,629. Nearly two thirds of admissions were for treatment of cellulitis with intravenous antibiotics. VLUs treated with surgical intervention did not significantly increase total cost ($12,304 vs $19,503; P > .05) but significantly reduced recurrence rates (34% vs 5%). There were three outliers who experienced complications after treatment of outflow obstruction that dramatically increased the total cost to $71,526. CONCLUSIONS: This economic analysis demonstrates the high true costs associated with modern treatment of VLU by aggressive medical and surgical techniques. Inpatient and outpatient facility fees, physician fees, and visiting nurse payments all contribute to the cumulative tally that results in these staggering direct costs for treatment of VLUs. The daily cost of treatment that accrues for the ongoing care of VLU patients until they are healed provides an economic rationale for initiatives that advance approaches seeking to provide more rapid wound healing. Our analysis also highlights the significant costs associated with treatment of infections and complications encountered in aggressive surgical interventions for patients with extensive chronic central venous occlusive disease. More aggressive early outpatient treatment of infections and refined criteria for selection of outflow stenting candidates may reduce total cost by preventing complications while improving outcomes. PMID- 26993538 TI - Validity of International Classification of Diseases, Ninth Revision, Clinical Modification codes for estimating the prevalence of venous ulcer. AB - BACKGROUND: The American Venous Forum issued a call to reduce the prevalence of venous ulcers (VUs) by 50% in 10 years. The objectives of this study were to determine the validity of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for VU and to estimate the prevalence of VU in a well-defined geographic population (Olmsted County, Minn). METHODS: Rochester Epidemiology Project resources and 18 VU ICD-9-CM codes were used to identify residents with possible VUs during the 2-year period 2010-2011 (n = 1551). The complete medical records in the community were reviewed for a 15% random sample (n = 227) of these residents, and on the basis of prespecified criteria, patients were categorized as a VU or non-VU case. Continuous and categorical variables were compared between groups by the two-sample t-test and chi(2) test. RESULTS: Ninety-three patients (41%) had active or healed VUs, 83 had non-VUs, and 51 never had ulcers but had stasis skin changes or skin infection. ICD-9-CM code 454.0 best identified VU cases (sensitivity, 24%; specificity, 100%). VU patients were older and heavier and more frequently had bilateral ulcers. On the basis of the random sample review, an estimated 635 patients had healed or active VUs during the 2-year period of the study. The prevalence of VUs in the Olmsted County population was estimated to be 210 per 100,000 person-years, with VU incidence (newly diagnosed ulcers) of 85 per 100,000 person-years. CONCLUSIONS: ICD-9-CM VU codes operated poorly for VU identification. VU surveillance for estimating trends in incidence and prevalence of VUs will require better methods. The estimated prevalence of VUs in Olmsted County is 210 per 100,000 person-years. New ulcers developed each year in 85 of 100,000 people, an incidence that seems to be higher than in the previous epidemiologic study in this population. PMID- 26993540 TI - Discussion. PMID- 26993539 TI - Outcomes after inferior vena cava thrombectomy and reconstruction for advanced renal cell carcinoma with tumor thrombus. AB - BACKGROUND: This report details the experience of a multidisciplinary surgical team in the management of stage III and stage IV renal cell carcinoma (RCC) with concomitant inferior vena cava (IVC) tumor thrombus. METHODS: A retrospective inquiry of our vascular database from 2003 to 2012 identified 55 surgical cases of stage III (n = 40) and stage IV (n = 15) RCC presenting with IVC tumor thrombus. Tumor characteristics and IVC tumor thrombus were evaluated by clinical staging and postoperative pathology staging. Patient demographics and surgical reconstruction are detailed. Cancer-specific outcomes consisted of oncologic surveillance with computed tomography or magnetic resonance imaging. A Clavien Dindo classification of early (<30 days) complications and mortality was recorded, including a review of secondary surgical interventions. RESULTS: According to the Novick classification of IVC tumor thrombus, there were 10 supradiaphragmatic (level IV), 20 intrahepatic (level III), and 25 infrahepatic (level II or I) tumor thrombi. Vena cava reconstruction was completed in 54 patients (98%), with one patient deemed unresectable. Vena cava control required cardiac bypass (n = 10), venovenous bypass (n = 4), or infrahepatic IVC control (n = 40). Reconstruction of the IVC was completed with two prosthetic interposition grafts for one stage IV thrombus and one stage III thrombus; two patch repairs were done for stage III thrombus, and there were 50 primary IVC repairs. All other IVC reconstructions were patent at a mean follow-up of 23 months. A single asymptomatic patient with primary IVC repair had estimated 30% IVC narrowing but no other measurable stenosis as detected by postoperative imaging. Three patients required reoperation (two for surgical site bleeding, one for small bowel fistula). Early surgical complications included Clavien-Dindo grades I (n = 3), II (n = 6), IIIa (n = 2), IIIb (n = 3), and V (n = 2). Regional retroperitoneal or distant recurrent RCC occurred in 26 patients (48%); a single patient demonstrating recurrent IVC tumor thrombus at 8 months required secondary IVC thrombectomy. All patients with tumor invasion of the IVC wall developed recurrent RCC, and no patient survived beyond 5 years. Early mortality was 3.6% (n = 2), with 27 patients (49%) dying within 24 months, resulting in an overall mortality for the cohort of 80% (n = 44) as established on routine regular postoperative surveillance. CONCLUSIONS: A multidisciplinary approach for the management of advanced RCC and IVC tumor thrombus helps optimize outcomes. Primary IVC repairs are possible in most patients, and IVC patency is good. Recurrent tumor thrombus rates are low; however, RCC tumor recurrence and mortality are high, especially among patients with advanced cancer with IVC wall invasion. PMID- 26993542 TI - Discussion. PMID- 26993541 TI - Bedside inferior vena cava filter placement by intravascular ultrasound in critically ill patients is safe and effective for an extended time. AB - BACKGROUND: Bedside inferior vena cava filter (IVCF) placement by intravascular ultrasound (IVUS) guidance has previously been shown to be a safe and effective technique, especially for critically ill patients, with initial experience of a prospectively implemented algorithm. The purpose of this study was to evaluate the effectiveness of IVUS-guided filter placement in critically ill patients with experience now extending out 5 years from implementation. METHODS: All patients undergoing bedside IVUS-guided IVCF placement from 2008 to 2012 were identified. Records were reviewed on the basis of IVCF reporting standards. Outcomes data including technical success, complications, and mortality were analyzed at 30 days. RESULTS: During the 5-year period, 398 patients underwent attempted bedside IVCF placement by IVUS. Technical feasibility was possible in 396 cases (99.5%); two bedside procedures were aborted because of inadequate IVUS visualization. Overall technical success was achieved in 393 of 396 (99.2%), with malpositioned IVCF in three cases. An optional IVCF was used in 372 (93.9%) and a permanent IVCF in 24 (6.1%). Single-puncture technique was performed in 388 (97.4%); additional dual access was required in 10 (2.6%). Periprocedural complications were rare (3.0%) and included malpositioning that required retrieval and repositioning or an additional IVCF (3), filter tilt >=20 degrees (4), arteriovenous fistulas (2), insertion site thrombosis (2), and hematoma (1). Comparison of the first 100 procedures performed within the sample population with the last 100 procedures revealed an overall success rate of 96% in the first 100 compared with 100% in the last 100 (P = .043). There were no deaths related to pulmonary embolism or IVCF-related problems. CONCLUSIONS: On the basis of 5 years of experience with bedside IVCF placement in critically ill patients, the IVUS-guided IVCF technique continues to be a safe and effective option in this high-risk population, with a time-dependent improvement in outcome measures. PMID- 26993543 TI - Reduction internal valvuloplasty is a new technical improvement on plication internal valvuloplasty for primary deep vein valvular incompetence. AB - OBJECTIVE: We describe a new technique of valve leaflet closure, reduction internal valvuloplasty (RIVAL), to treat primary deep vein valvular incompetence in patients with C6 venous disease. METHODS: The RIVAL method involves excision of redundant valve and suturing of the freshened edge to the wall of the valve station instead of plication at the commissural junctions. Since January 2008, RIVAL has been successfully performed on 44 incompetent deep vein valves in 18 consecutive patients (25 limbs). All patients had C6 venous ulcers of a minimum 3 months' duration. RESULTS: On mean follow-up of 1 year (clinical assessment of venous ulcer healing and color-coded duplex scans at 1, 6, 12, 18, and 24 months) of the 44 valves repaired by reduction valvuloplasty, all 44 valves (100%) maintained full patency. Forty-two valves (95.4%) were competent, achieving a valve closure time <1 second with no reflux at the target valves on Valsalva maneuver in the reverse Trendelenburg and upright positions, and their intervalvular distances were reduced to >60% of preoperative levels. Eighty-eight percent of all ulcers (22 of 25) healed within 9 weeks of surgery without any recurrence in the follow-up period. There was no valve thrombosis or resorption seen with this method. CONCLUSIONS: The RIVAL technique represents a significant advancement over the traditional existing valve plication techniques. It enables accurate anatomic fashioning and suturing of valve cusps and results in excellent competency and ulcer healing rates with fewer complications in our early experience. Further follow-up is anticipated to define its long-term role in the management of C6 venous disease. PMID- 26993544 TI - Primary avalvular varicose anomalies are a naturally occurring phenomenon that might be misdiagnosed as neovascular tissue in recurrent varicose veins. AB - OBJECTIVE: The objective of this study was to report a phenomenon in patients with primary varicose veins that resembles neovascular tissue in postsurgical recurrences-primary avalvular varicose anomalies (PAVA). METHODS: Between March 2012 and July 2013, 756 patients (122 men, 634 women) with primary varicose veins (mean age, 53 years; range, 18-89 years) underwent duplex ultrasonography with retrospective analysis of their reflux patterns. We diagnose PAVA as small, refluxing vessels in legs with primary varicose veins and no history of surgery, trauma, or infection in the area that show one or more of three patterns of distribution: lymph node pattern-PAVA arising directly from groin lymph nodes; peritruncal pattern-PAVA wrapping around the great, small, or anterior accessory saphenous veins; and atypical pattern. PAVA are predominantly found within the saphenous fascia, but components have been found to emerge into the superficial and deep venous compartments. RESULTS: We analyzed results from 1398 legs (756 patients). Sixty-four legs (4.6%) in 58 patients exhibited PAVA, bilateral in six patients and unilateral in 52 patients. Lymph node involvement and peritruncal PAVA were seen in 23.4% and 70.3% of legs, respectively. The small saphenous vein was the most common truncal vein to be involved (48.9% of peritruncal cases). More than one pattern of PAVA could be observed in seven legs. Of the 48 women with PAVA, 42% had concurrent pelvic vein reflux. CONCLUSIONS: Neovascularization has been identified as a major cause of clinically recurrent varicose veins. Neovascular tissue has been described after endovenous thermoablation. We suggest that this might represent PAVA undetected preoperatively in some cases. PAVA are thin-walled, serpiginous, incompetent vessels that resemble neovascular tissue. We conclude that neovascularization should be diagnosed as a source of recurrence after endovenous surgery only if PAVA had been actively looked for, and excluded, in the preoperative diagnostic duplex ultrasound examination. PMID- 26993545 TI - Reflux in the below-knee great saphenous vein can be safely treated with endovenous ablation. AB - BACKGROUND: Intervention on the great saphenous vein (GSV) has traditionally been limited to the above-knee (AK-GSV) segment for fear of saphenous neuralgia in spite of incompetence demonstrated in the below-knee (BK-GSV) segment. Residual symptoms and need for reintervention are reported to result in nearly half the patients if the refluxing BK-GSV is ignored. Experience with endovenous ablation of the BK-GSV at the time of AK-GSV treatment is sparsely reported in the literature. The aim of this study was to evaluate the safety of endovenous ablation of the refluxing BK-GSV. METHODS: Data from consecutive patients treated with superficial venous ablation during a 48-month period from January 2010 to December 2013 were retrospectively reviewed. Demographic and procedure-related outcome and complication data were analyzed specifically for patients undergoing BK-GSV interventions. RESULTS: A total of 550 patients were treated with superficial venous ablation during the study period. Of those, 61 (79 limbs) underwent BK-GSV ablation for reflux at this site. There were 36 women and 25 men (mean age, 55 years). Median Clinical, Etiologic, Anatomic, and Pathologic (CEAP) score was 3.4; 43 limbs were treated for symptomatic varicose veins (C 1-3) and 36 for advanced venous insufficiency (C 4-6); 14 limbs (18%) were treated for recurrent symptomatic varicose veins or venous insufficiency after prior superficial venous intervention with AK-GSV ablation, sclerotherapy, or stripping. Comorbidities included obesity (54%) with mean body mass index of 30.7 (range, 19 to 52), obstructive sleep apnea (10%), pulmonary hypertension (3%), and congestive heart failure (3%). Ablation was performed in 77 limbs (99%) with the VenaCure EVLT laser vein treatment (AngioDynamics, Queensbury, NY) and in two limbs by radiofrequency ablation with ClosureFAST system (VNUS Medical Technologies, San Jose, Calif). The mean length of GSV ablated was 51.2 cm (range, 26-67 cm). Endovenous ablation was performed concomitantly on 22 accessory GSVs (28%) and 10 incompetent perforators (13%). Ambulatory stab phlebectomy of branch varicosities was performed simultaneously in 59 limbs (75%). All veins treated were evaluated with ultrasound on postprocedure day 1, and no evidence of endovenous heat-induced thrombosis was detected. Eight patients (10%) went on to have preplanned sclerotherapy treatment for small branch varicosities. Postoperative paresthesia occurred in three patients (4%) and resolved within 4 weeks. Wound infection in three (4%) stab phlebectomy wounds resolved with oral antibiotic therapy. Follow-up surveillance ultrasound was available in 32 of 79 limbs that were >6 months from the procedure. Partial late recanalization was noted in four of 32 limbs, but no patient had recurrent symptoms requiring repeated endovenous ablation during this period. CONCLUSIONS: Endovenous ablation of the refluxing BK-GSV segment can be performed safely with minimal complications. Consideration should be given to concomitant ablation of the BK-GSV in treatment of patients with varicose veins with reflux extending to the BK segment of the GSV to improve long-term outcomes. PMID- 26993546 TI - Endovenous laser ablation of great and small saphenous vein incompetence with a 1470-nm laser and radial fiber. AB - OBJECTIVE: Endovenous laser ablation (EVLA) of great (GSV) and small saphenous vein (SSV) chronic insufficiency with 1470-nm diode laser and radial fiber yields good short-term results. The aim of this study was to assess its efficacy after at least 12 months of follow-up. METHODS: We performed a prospective interventional cohort study in an ambulatory care/day surgery setting. Consecutive patients with chronic, symptomatic GSV or SSV insufficiency were treated by EVLA with a 1470-nm diode laser and a radial fiberoptic. Patients were recruited between 2008 and 2011, and the follow-up was completed in 2012. All patients underwent clinical and echo color Doppler evaluations during follow-up. The primary outcome was the incidence of echo color Doppler-confirmed failures during follow-up. We also investigated potential associations between failures and patients' characteristics, echo color Doppler findings, or surgical features. The secondary outcome was the postoperative pain course. RESULTS: The planned 12 month follow-up was completed in 372 patients. Echo color Doppler-confirmed failures occurred in 37 (12%) of 310 patients with GSV insufficiency, whereas none of 62 patients with SSV insufficiency experienced a failure. Multiple Cox proportional hazards regression analysis showed a significant association of failures with a Clinical, Etiologic, Anatomic, and Pathologic class C >=4 and a mean confluence of the superficial inguinal veins diameter >=9 mm in patients with GSV insufficiency. Postoperative pain course was favorable. More than two thirds of the patients were asymptomatic at 7 days. CONCLUSIONS: EVLA with 1470 nm diode laser and radial fiberoptic is effective for treatment of GSV and especially SSV insufficiency and is well tolerated by the patients. PMID- 26993547 TI - Pelvic venous reflux is a major contributory cause of recurrent varicose veins in more than a quarter of women. AB - BACKGROUND: Leg varicose veins are associated with pelvic venous reflux in approximately 20% of women who have had children. However, most venous units do not routinely look for pelvic venous reflux or treat it. We aimed to investigate what proportion of patients with recurrent varicose veins and a history of open surgery have pelvic venous reflux as a major contributing cause of their recurrence. METHODS: A retrospective study was performed of all patients referred in the previous year with recurrent varicose veins or venous reflux disease who had previously had open surgery performed elsewhere. All patients had routine lower limb venous duplex ultrasonography, and those found to have reflux of pelvic origin underwent transvaginal duplex ultrasonography. Each case was assessed by a consultant vascular surgeon, and the major cause (or causes, if more than one) of the recurrent varicose veins was noted. RESULTS: A total of 109 patients with recurrent varicose veins in 172 legs were analyzed (mean age, 53.9 years; female-to-male ratio, 97:12). Patients were divided into four groups: group 1, all patients; group 2, female patients; group 3, female patients with children; and group 4, female patients with children who had not had hysterectomy. Pelvic venous reflux was found to be a major contributing cause of recurrent varicose veins in 44 of 172 legs (25.6%). This rose to 43 of 154 legs (27.9%) in group 2, 40 of 131 legs (30.5%) in group 3, and 37 of 111 legs (33.3%) in group 4. CONCLUSIONS: Pelvic venous reflux is a major contributing cause of recurrent varicose veins after open surgery that has rarely been reported previously. In view of this finding, we suggest that a duplex ultrasound protocol, incorporating a transvaginal duplex examination of the ovarian and internal iliac veins, be adopted for the investigation of pelvic venous reflux in female patients presenting with symptomatic leg varicose veins with duplex observed reflux entering the leg vein pattern from the pelvis. In the event that it is found, we suggest that treatment and resolution of this source of venous reflux be considered before any intervention for the leg varicose veins, surgical or otherwise. PMID- 26993548 TI - Calf volume changes with venous occlusion air plethysmography in assessment of patients after deep venous thrombosis. AB - BACKGROUND: This is an analysis of the hemodynamic response of post-thrombotic legs to a sustained thigh compression and quick-release maneuver. This is an integral part of the investigation of venous occlusion plethysmography that has been promoted as a way of assessing the venous return. The aim was to quantify the venous volume changes in patients after deep venous thrombosis (DVT) and to determine whether refluxing legs differed from obstructed legs. METHODS: The inflow and outflow air plethysmography tracings of 332 of 519 legs were examined retrospectively. These tracings from 192 patients were performed between 1989 and 1999. The median age was 51 (17-89) years; 65% of the patients were men, and 52% were left legs. The retrospective clinical class distribution (%) by the Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification was as follows: C0 = 5.4, C2 = 3.3, C3 = 68.4, C4 = 13, C5 = 3.6, C6 = 6.3. Inclusion criteria were a history of DVT and a duplex ultrasound examination documenting the site and type of deep venous disease. Ascending phlebography was performed in 28% of patients to complement duplex ultrasound in assessing the site of disease. Reflux was defined as reverse flow (>1 second) and obstruction as luminal narrowing, wall irregularity, or luminal echogenic material. Air plethysmography was performed in the supine position. After calibration with 100 mL of air, a thigh cuff was inflated to 80 mm Hg, and the resulting increase in calf volume was recorded by the sensor calf cuff with an ink trace on graphic paper. At the volume plateau, the thigh cuff was deflated suddenly to record the decrease in calf volume. RESULTS: Reflux alone was identified in 19.6% of limbs and obstruction alone in 42.2%. Iliofemoral involvement was identified in 56.6%. The thigh compression/release maneuver caused a significant median (interquartile range) net reduction in calf volume by 9 (5-15) mL (P < .0005, Wilcoxon). The outflow volume was significantly greater than the inflow volume overall and also when legs were separated into categories on the basis of their site and type of disease (P < .0005, Wilcoxon). There was no significant difference in calf volume change in legs with iliofemoral involvement compared with those with distal disease. However, pure refluxing legs had significantly greater inflow and outflow volumes compared with legs with pure obstruction (P < .0005), with a median (interquartile range) reduction in calf volume of 13 (8-18) mL (reflux group) vs 7 (2-13) mL (obstruction group) (P < .0005, Mann-Whitney). CONCLUSIONS: Thigh compression significantly improves the venous return in patients after DVT evidenced by a greater absolute reduction of calf volume. This change was significantly greater in pure refluxing legs than in those with obstruction alone. PMID- 26993549 TI - Measurement of calf muscle oxygenation during light-intensity exercise in patients with post-thrombotic syndrome. AB - BACKGROUND: Near-infrared spectroscopy (NIRS) provides continuous noninvasive monitoring of changes in the levels of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) in tissues. The purpose of this study was to investigate changes in calf muscle O2Hb and HHb levels during standing and exercise in the follow-up of deep venous thrombosis (DVT). METHODS: Forty-three patients with a first episode of unilateral proximal DVT were included. Final clinical manifestations were evaluated at a mean follow-up point of 53 months after diagnosis of DVT, and post-thrombotic syndrome (PTS) was considered to be present if the Villalta score was >5. Moreover, to assess the severity of PTS, the revised Venous Clinical Severity Score (VCSS) was employed. NIRS was used to measure changes in the levels of O2Hb and HHb in calf muscle. On standing, increases in O2Hb and HHb were calculated by subtracting the baseline value from the maximum value (DeltaO2Hbst and DeltaHHbst). The times taken for the O2Hb and HHb concentrations to become maximal (TO2Hbst, and THHbst) were also measured. During 10 tiptoe movements, the relative change in O2Hb was calculated by subtracting the value measured at the end of exercise from the value measured at the beginning of exercise (DeltaO2Hbex). On the other hand, 10 tiptoe movements produced venous expulsion (DeltaHHbEex) and a subsequent retention (DeltaHHbRex). The oxygenation index (HbD; HbD = O2Hb - HHb) was also calculated at the end of standing and at the end of 10 tiptoe movements (DeltaHbDst and DeltaHbDex). RESULTS: Among the 43 limbs evaluated, 21 had PTS. On standing, the DeltaHbDst was significantly decreased in patients with PTS relative to the patients without PTS (12 +/- 8, 22 +/- 11 MUmol/L; P = .001). The TO2Hbst was also significantly reduced in patients with PTS relative to those without (43 +/- 41, 107 +/- 58 seconds; P = .001). During 10 tiptoe movements, the DeltaHHbEex was significantly reduced in patients with PTS relative to those without (-2 +/- 1, -3 +/- 3 MUmol/L; P = .016). Similarly, the DeltaHHbRex was significantly increased in patients with PTS relative to those without (8 +/- 7, 3 +/- 2 MUmol/L; P = .001). Furthermore, falls in DeltaHbDex were more pronounced in patients with PTS (-10 +/- 16, 10 +/- 10 MUmol/L; P < .001). NIRS-derived TO2Hbst (r = -0.568; P < .001) and DeltaHbDex (r = -0.645; P < .001) showed strong inverse correlations with VCSS. Similarly, NIRS-derived DeltaHHbEex (r = 0.409; P < .01) and DeltaHHbRex (r = 0.476; P < .01) showed moderate positive correlations and DeltaHbDst (r = 0.422; P < .01) had a moderate inverse correlation with VCSS. CONCLUSIONS: Changes in O2Hb and HHb concentrations differ between patients with and without PTS. The reduced TO2Hbst may indicate impairment of the venoarteriolar reflex in patients who have PTS. Furthermore, severe falls in HbD in patients with PTS might reflect the pain of venous claudication. These findings may have implications for investigations of the microcirculation in the context of post thrombotic sequelae. PMID- 26993550 TI - Low-concentration detergent sclerosants stimulate white blood cells and release proinflammatory and proangiogenic cytokines in vitro. AB - OBJECTIVE: The objective of this study was to investigate the effects of the detergent sclerosants sodium tetradecyl sulfate (STS) and polidocanol (POL) on the release of proinflammatory and angiogenic mediators from circulating blood cells. METHODS: Whole blood, platelet-rich plasma, platelet-poor plasma, and suspensions of polymorphonuclear cells (PMNCs) and mononuclear cells (MNCs) were incubated with varying concentrations of sclerosants. Enzyme-linked immunosorbent assay was used to detect the release of interferon-gamma (IFN-gamma); tumor necrosis factor-alpha (TNF-alpha); interleukins (IL) 1alpha, 1beta, 6, 8, and 17; vascular endothelial growth factor (VEGF); and basic fibroblast growth factor. Leukocyte activation was assessed by flow cytometry. RESULTS: IFN-gamma and TNF alpha were released from STS-stimulated PMNCs at high (387 ng/mL; P < .01) and modest (232 ng/mL; P < .05) quantities, respectively. Both sclerosants induced a weak response in MNCs, releasing minor quantities of IL-1alpha (STS, 18.2 ng/mL; POL, 14.0 ng/mL), IFN-gamma (STS, 41.7 ng/mL; POL, 27.7 ng/mL), and TNF-alpha (STS, 29.7 ng/mL; POL, 14.0 ng/mL). POL at a wide range of concentrations and in all sample types tested stimulated the release of VEGF, whereas the effect of STS was limited to low concentrations and not detected in MNCs. Both agents stimulated moderate release of IL-8 from PMNCs (STS, 223.3 ng/mL, P < .001; POL, 84.23 ng/mL, P < .05). Neither agent induced a significant rise in basic fibroblast growth factor, IL-6, or IL-17. STS at low concentrations increased the expression of CD11b in both PMNCs and MNCs, suggestive of cellular activation. The activating effect of POL was limited to MNCs. CONCLUSIONS: STS demonstrated proinflammatory activity mediated primarily by IFN-gamma released from PMNCs and MNCs. POL had a weak proinflammatory effect limited to MNCs. Both sclerosants (POL > STS) induced a proangiogenic response mediated by VEGF. PMID- 26993551 TI - Multimodal therapy in the treatment of a venolymphatic malformation of the axilla and chest wall in an infant. AB - We report our staged multimodal treatment of a female infant with a very large complex venolymphatic malformation of the axilla and chest wall. We successfully managed the patient's severely restricted arm mobility and consumptive coagulopathy with surgical debulking followed by medical therapy with the mammalian target of rapamycin inhibitor sirolimus. The diseased burden reduced in size throughout therapy, and hematologic parameters reached and maintained normal levels. Normal health and limb functionality were restored with no observed adverse side effects of medical therapy. This case presents a previously unreported and potentially promising method to treat severe vascular malformations. PMID- 26993552 TI - Endovascular treatment of a thrombosed intracardiac vena cava filter. AB - Intracardiac migration of a vena cava filter (VCF) is a rare but potentially fatal complication. We describe a unique case of intracardiac migration of a permanent VCF with extensive thrombus propagating into the inferior vena cava and right atrium. Percutaneous thrombectomy with the AngioVac (AngioDynamics, Latham, NY) device was performed, and the permanent VCF was percutaneously removed. PMID- 26993553 TI - Preaortic iliac vein and double inferior vena cava. PMID- 26993554 TI - Embolization of iliofemoral thrombus during diagnostic venography. PMID- 26993555 TI - Surgical procedures in lymphedema management. AB - OBJECTIVE: Lymphedema has a high incidence and various causes. It reduces patients' quality of life and productivity and currently lacks a cure. Management is based on lifelong physical therapies. Many surgical procedures have been proposed for lymphedema without significant acceptance. This study evaluates surgical procedures aimed at the management of lymphedema and highlights present evidence. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Grading of Recommendations Assessment, Development and Evaluation consensus, a systematic literature search (MEDLINE and The Cochrane Library) was performed to identify studies evaluating treatment outcomes after lymphedema surgery. The authors evaluated all articles found with the keywords "lymphedema" and "surgery," including experimental studies in animals. Cross referencing was made. Next, a protocol was created to assess the degree of quality of publications in this field. An overview of the complete medical literature was performed. Thereafter, publications meeting inclusion criteria were attributed a score according to the assessment protocol. This allowed an overview of the scientific quality of all surgical procedures for lymphedema. RESULTS: A total of 108 article texts were read and 70 publications included in this study according to predefined criteria. Lymphedema operative procedures were classified according to type. The outcomes highlighted the importance of individual patient analysis, as most interventions are not sufficiently studied to sustain clinical recommendations. CONCLUSIONS: Risk factors for acquired lymphedema, such as lymph node excision and radiation therapy, are well identified and should allow primary prevention. Improved diagnosis, classification, standardized volume measurement, staging, and follow up of lymphedema patients can facilitate their management and allow valid retrospective studies. Currently, there is no evidence of any treatment yielding high long-term cure rates. Therefore, lymphedema management must be based on interdisciplinary approaches, with curative or palliative therapy options discussed openly with the patient. Therapeutic plans should not exclude surgery. Nevertheless, additional studies are recommended to prove the validity of some surgical approaches. PMID- 26993556 TI - Report from the 2013 meeting of the International Compression Club on advances and challenges of compression therapy. AB - The International Compression Club, a collaboration of medical experts and industry representatives, was founded in 2005 to develop consensus reports and recommendations regarding the use of compression therapy in the treatment of acute and chronic vascular disease. During the recent meeting of the International Compression Club, member presentations were focused on the clinical application of intermittent pneumatic compression in different disease scenarios as well as on the use of inelastic and short stretch compression therapy. In addition, several new compression devices and systems were introduced by industry representatives. This article summarizes the presentations and subsequent discussions and provides a description of the new compression therapies presented. PMID- 26993558 TI - Events of interest. PMID- 26993557 TI - Managing and improving efficiency of an outpatient vascular laboratory. AB - Noninvasive vascular diagnostic testing is efficient and cost-effective, and it is an integral part of vascular surgery practice. Integration of the laboratory into the practice can add significant income to a practice as well as increase the quality of the patient's experience. Maintaining a successful vascular laboratory is a key component of the practice's remaining competitive in an ever changing health care system. Attention must be paid to staffing, operations, financial performance, revenue cycle, and patient and referring physician satisfaction to grow the business. PMID- 26993560 TI - Information for readers. PMID- 26993561 TI - Circulatory Management Focusing on Preventing Intraventricular Hemorrhage and Pulmonary Hemorrhage in Preterm Infants. AB - The goal of modern neonatal care of extremely preterm infants is to reduce mortality and long-term neurological impairments. Preterm infants frequently experience cerebral intraventricular or pulmonary hemorrhage, which usually occurs within 72 hours after birth and can lead to long-term neurological sequelae and mortality. These serious hemorrhagic complications are closely related to perinatal hemodynamic changes, including an increase in the afterload on the left ventricle of the heart after the infant is separated from the placenta, and an increased preload from a left-to-right shunt caused by a hemodynamically significant patent ductus arteriosus (PDA). The left ventricle of a preterm myocardium has limited ability to respond to such an increase in afterload and preload, and this can result in cardiac dysfunction and hemodynamic deterioration. We suggest that delayed umbilical cord clamping or umbilical cord milking to maintain optimal blood pressure and systemic blood flow (SBF), careful assessment to keep the afterload at an acceptable level, and a strategy of early targeted treatment of significant PDA to improve perfusion during this critical time period may reduce or prevent these serious complications in preterm infants. PMID- 26993562 TI - Childhood Albuminuria and Chronic Kidney Disease is Associated with Mortality and End-Stage Renal Disease. AB - BACKGROUND: We do not yet fully grasp the significance of childhood albuminuria. Based on mass urinary screening (MUS) using albumin-specific dipsticks in school children, we studied the independent association of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in children with chronic kidney disease (CKD). METHODS: A prospective cohort of 5351 children with albuminuria detected by school MSU during the period 1992-1996, followed up to 2009. RESULTS: Cumulative mortality rate, prevalence of CKD, and ESRD were higher in children with albuminuria than those without. Albuminuria category was associated with the risk of mortality [hazard ratio (HR) 3.4] and ESRD (HR 3.24). Lower eGFR and albuminuria predicted mortality and ESRD among children with albuminuria and CKD. We found that being below a threshold of 45 mL/min/1.73 m(2) was significantly associated with ESRD. The highest renal function decline, along with the steepest slope of cumulative ESRD number, occurred in Stage 3, the critical point in renal progression. Risk factors for renal progression among different age groups with albuminuria were hypercholesterolemia and low serum albumin at 7-17 years of age. Beyond 18 years of age, besides the risk factor, a higher fasting blood sugar (BS) was also noted. CONCLUSION: Childhood albuminuria is a risk factor for CKD in later life, albuminuria provides additional prognostic information, and complications of CKD should be defined in each case. PMID- 26993563 TI - Single and paired-pulse electrical stimulation during invasive EEG recordings. AB - Invasive EEG recordings are frequently required during the presurgical exploration of patients with drug-resistant focal epilepsy in order to clarify the epileptic zone location. Intracranial direct electrical stimulations (DES) induce EEG and/or clinical responses that participate in this evaluation. Clinical DES protocols (1Hz and/or 50Hz) trigger massive cortical activation that can elicit seizures, after-discharges or complex clinical signs. In contrast, low energy (<1Hz) protocols activate more localized cortical regions using single pulse electrical stimulations (SPES). SPES can elicit two main types of responses. Cortico-cortical evoked potentials (CCEPs) correspond to highly consistent early responses, appearing before 100ms after stimulation, with fixed latency; they are considered physiological and assess the effective connectivity between the recorded regions. Late responses appear after 100ms; they are rare, inconsistent with variable latency and are suggestive of an underlying epileptogenic cortex. Paired-pulse stimulation paradigm associates a conditioning and a test stimulation to induce intracortical inhibition or facilitation by modifying the response amplitude. Largely used in transcranial magnetic stimulation, it has rarely been applied to CCEP although the mechanisms put in place seem highly similar. Low frequency intracerebral stimulations allow analysing brain connectivity and cortical excitability with a high temporal and spatial resolution. The development of new stimulation protocols and the combination with imaging or statistical techniques recently offered promising results. PMID- 26993564 TI - Sleep quality assessment in 35 Parkinson's disease patients in the Fann Teaching Hospital, Dakar, Senegal. AB - INTRODUCTION: Sleep disorders are diverse in Parkinson's disease. We aimed to assess the quality of sleep in patients with Parkinson's disease in an African population. METHODS: In a transversal and prospective study from April to June 2014, all parkinsonian patients followed at the Fann Teaching Hospital Neurology Clinic (Dakar, Senegal) were assessed using the Hoehn and Yahr's scale and filled out the following questionnaires: Parkinson's disease sleep scale (PDSS), the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). A PDSS score<82 (or a subscore<5) and a PSQI score>5 indicated poor quality or impaired sleep. An ESS score>10 indicated excessive daytime sleepiness. We used the Pearson coefficient to search for correlation between age, disease stage, disease duration, and the importance of sleep impairment. RESULTS: Hoehn and Yahr staging was 2.42+/-0.90 in the 35 patients (60% male, mean age 65.7+/-7.4years, disease duration 32.4+/-23.4months). The mean total PDSS score was 99.5+/-24.1 and 74.3% of the patients had an abnormally high PSQI score, indicating high frequency and intensity of sleep disorders. Most frequent disorders were pain or cramps interrupting sleep, night waking to urinate and fatigue or sleepiness on waking. Patients exhibited excessive diurnal sleepiness in 22.9% of the cases; they often had an abnormal PSQI score. Both the total PDSS score and the difficulty to sleep increased with disease stage, but not with age or disease duration. CONCLUSION: We found evidence of major alteration of sleep quality in Senegalese Parkinson patients. PMID- 26993565 TI - Severe neonatal seizures: From molecular diagnosis to precision therapy? AB - Early onset epileptic encephalopathies (EOEE) are heterogeneous group of severe epilepsies that still need to be better defined and characterized. On a genetic point of view, several dozen of genes have been associated with EOEE, and to date, it is difficult to find a common mechanism to explain EOEE. In this short review, we show that two mains genes are involved in EOEE: STXBP1 and KCNQ2. Focusing on KCNQ2 related EOEE, we show that a relatively similar phenotype can be related to various consequences of mutations on a single gene. This will probably challenge the treatment of EOEE patients. PMID- 26993566 TI - Slowing of information processing speed without motor slowing in multiple sclerosis observed during two crossing-off tasks. AB - INTRODUCTION: Slowing of information processing speed (IPS) is often considered one of the primary deficits seen in multiple sclerosis (MS). IPS is usually measured by tasks that involve many cognitive functions. The aim of this study was to determine whether similar IPS slowing can also be observed during two simple, timed, psychomotor crossing-off tasks. METHOD: The Crossing-Off Test (COT), a simple psychomotor task, was performed under two conditions (COT1 corresponded to writing habits, COT2 used horizontal sweeping) in 25 relapsing remitting MS patients (EDSS 0-1) and 25 healthy controls. RESULTS: The MS group compared with the control group was impaired on COT1 (P=0.0043) and not on COT2 (P=0.4), and the COT1 performance of MS patients with EDSS 1 was more impaired than those of patients with EDSS 0 (P=0.008). DISCUSSION/CONCLUSION: These results indicate that only some of the IPS cognitive subcomponents linked with COT1 tasks are initially involved in the slowing of IPS during MS, suggesting that different mechanisms are involved in each tested version of the COT. PMID- 26993567 TI - Spinal cord venous infarctions and paraproteinemia. PMID- 26993568 TI - Non-pharmacological medical treatment in pediatric epilepsies. AB - The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet that has been employed as a non-pharmacologic therapy for refractory epilepsy. Several multicenter and two randomized studies have demonstrated the efficacy of the ketogenic diet and the modified Atkins diet for children and adolescent with pharmacoresitant epilepsy. In order to facilitate patient tolerability and palatability, the diet protocols are gradually modified including changes in ratios of the fat versus non-fat components and the initiation of the diet with or without fasting. The modified Atkins diet is now used as an alternative diet. A randomized trial establishing the efficacy of the modified Atkins diet is now available. More recently, the low glycemic index diet seems to be used successfully for pharmacoresistant epilepsy but there are currently only open studies. Looking at the clinical efficacy of dietary treatments, the studies usually report a greater than 50% reduction in seizure frequency in about half of patients at 3 months under diet. Most of the patients who are responders to the ketogenic diet exhibited a decrease in seizure frequency within two months of treatment onset. Efficacy of the ketogenic diet has also been reported for teenager and adult patients. Dietary treatment of epilepsy should not be considered as a last chance treatment. It can be used during the investigation for epilepsy surgery even in case of structural abnormalities. In some epilepsy syndromes such as infantile spasms, myoclonic-astatic epilepsy and refractory status epilepticus, an early use seems helpful. The exact underlying mechanisms are unknown and remain a topic of active research. PMID- 26993569 TI - Anaemia and cardiac surgery. PMID- 26993570 TI - Does a new implant design with more physiological kinematics provide better results after knee arthroplasty? AB - BACKGROUND: Improved knee kinematics is one of the major goals to obtain better satisfaction after total knee arthroplasty. This study examined whether a guided motion knee design improves functional outcome and satisfaction as compared to a conventional design. METHODS: In a retrospective manner, from January 2005 to December 2008, patients with two different kinematic TKA designs were enrolled. The 150 patients were divided into two groups: guided motion group (77) with kinematic design (Journey) and control group (73) with no kinematic design (LCS). All the patients had the same surgical technique and postoperative protocols. The functional and radiographic results were interpreted with the Hospital for Special Surgery (HSS) knee score and WOMAC score. RESULTS: After a mean follow-up of 84.2months, the guided motion group had higher mean postoperative range of motion (p=0.022), functional status in the WOMAC function subscale (p=0.002), but had higher residual pain in the WOMAC pain subscale (p=0.018 and p=0.013) and higher iliotibial band syndrome incidence (6.6% vs 0%; p=0.02). There were no significant differences in HSS score between the two groups. No differences were seen between groups in patient satisfaction in the WOMAC total score (p=0.46) and survival rate. CONCLUSION: The guided motion design can improve functional status according to WOMAC but not to HSS knee scores. Poorer pain scores and no higher patient satisfaction were observed with this kinematic design. PMID- 26993571 TI - Myositis ossificans after navigated knee surgery: A report of two cases and literature review. AB - Computer-assisted surgery is now a common procedure in the field of orthopedics. We present two patients who developed myositis ossificans, a rare complication after navigated knee surgery. Due to careful follow-up and conservative treatment, surgical excision was avoided in both patients with good clinical results. Development of myositis ossificans after navigated knee surgery should be considered in cases of thigh pain and restricted range of motion of the knee. PMID- 26993572 TI - Artificial Intelligence and Medical Research: Time to Aim Higher? PMID- 26993573 TI - The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases? AB - One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex involvement of autophagy and ER stress in brain diseases. Novel pathways to modulate protein misfolding are discussed including the relation between aging and growth factor signaling. This article is part of a Special Issue entitled SI:Autophagy. PMID- 26993574 TI - Evidence for Reduced Fatigue Resistance of Contemporary Rotary Instruments Exposed to Body Temperature. AB - INTRODUCTION: The purpose of this study was to evaluate the effect of 2 different temperatures (20 degrees C and 37 degrees C) on the cyclic fatigue life of rotary instruments and correlate the results with martensitic transformation temperatures. METHODS: Contemporary nickel-titanium rotary instruments (n = 20 each and tip size #25, including Hyflex CM [Coltene, Cuyahoga Falls, OH], TRUShape [Dentsply Tulsa Dental Specialties, Tulsa, OK], Vortex Blue [Dentsply Tulsa Dental Specialties], and ProTaper Universal [Dentsply Tulsa Dental Specialties]) were tested for cyclic fatigue at room temperature (20 degrees C +/ 1 degrees C) and at body temperature (37 degrees C +/- 1 degrees C). Instruments were rotated until fracture occurred in a simulated canal with an angle curvature of about 60 degrees and a radius curvature of 3 mm; the center of the curvature was 4.5 mm from the instrument tip. The number of cycles to fracture was measured. Phase transformation temperatures for 2 instruments of each brand were analyzed by differential scanning calorimetry. Data were analyzed using the t test and 1-way analysis of variance with the significance level set at 0.05. RESULTS: For the tested size and at 20 degrees C, Hyflex CM showed the highest resistance to fracture; no significant difference was found between TRUShape and Vortex Blue, whereas ProTaper Universal showed the lowest resistance to fracture. At 37 degrees C, resistance to fatigue fracture was significantly reduced, up to 85%, for the tested instruments (P < .001); at that temperature, Hyflex CM and Vortex Blue had similar and higher fatigue resistance compared with TRUShape and ProTaper Universal. CONCLUSIONS: Under the conditions of this study, using a novel testing design, immersion in water at simulated body temperature was associated with a marked decrease in the fatigue life of all rotary instruments tested. PMID- 26993575 TI - Attitudes and behaviour towards convenience food and food waste in the United Kingdom. AB - Households in the UK discard much food. A reduction in such waste to mitigate environmental impact is part of UK government policy. This study investigated whether household food waste is linked to a lifestyle reliant on convenience food in younger consumers. A survey of 928 UK residents aged 18-40 years and responsible for the household food shopping (male n = 278; female n = 650) completed an online questionnaire designed to measure attitudes to convenience food and to quantify household food waste. Cluster analysis of 24 food-related lifestyle factors identified 5 consumer groups. General linear modelling techniques were used to test relationships between the purchase frequency of convenience food and household food waste. From the cluster analysis, five distinct convenience profiles emerged comprising: 'epicures' (n = 135), 'traditional consumers' (n = 255), 'casual consumers' (n = 246), 'food detached consumers' (n = 151) and 'kitchen evaders' (n = 141). Casual consumers and kitchen evaders were the most reliant on convenience food and notably were the most wasteful. The demographic profile of kitchen evaders matched the population groups currently targeted by UK food waste policy. Casual consumers represent a new and distinct group characterised by "buy a lot and waste a lot" behaviour. Household size, packaging format, price-awareness and marketing all appear to influence levels of food waste. However, it seems that subtle behavioural and sociocultural factors also have impact. Further research is needed to elucidate the factors that mediate the positive association between the purchase of convenience food and reported food waste in order to inform food waste policy and initiatives. PMID- 26993576 TI - Kainate-induced network activity in the anterior cingulate cortex. AB - Anterior cingulate cortex (ACC) plays a pivotal role in higher order processing of cognition, attention and emotion. The network oscillation is considered an essential means for integration of these CNS functions. The oscillation power and coherence among related areas are often dis-regulated in several psychiatric and pathological conditions with a hemispheric asymmetric manner. Here we describe the network-based activity of field potentials recorded from the superficial layer of the mouse ACC in vitro using submerged type recordings. A short activation by kainic acid administration to the preparation induced populational activities ranging over several frequency bands including theta (3-8Hz), alpha (8 12Hz), beta (13-30Hz), low gamma (30-50Hz) and high gamma (50-80Hz). These responses were repeatable and totally abolished by tetrodotoxin, and greatly diminished by inhibitors of ionotropic and metabotropic glutamate receptors, GABAA receptor or gap-junctions. These observations suggest that the kainate induced network activity can be a useful model of the network oscillation in the ACC circuit. PMID- 26993577 TI - Detectors for evaluating the cellular landscape of sphingomyelin- and cholesterol rich membrane domains. AB - Although sphingomyelin and cholesterol are major lipids of mammalian cells, the detailed distribution of these lipids in cellular membranes remains still obscure. However, the recent development of protein probes that specifically bind sphingomyelin and/or cholesterol provides new information about the landscape of the lipid domains that are enriched with sphingomyelin or cholesterol or both. Here, we critically summarize the tools to study distribution and dynamics of sphingomyelin and cholesterol. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26993578 TI - Triacylglycerol turnover in the failing heart. AB - No longer regarded as physiologically inert the endogenous triacylglyceride (TAG) pool within the cardiomyocyte is now recognized to play a dynamic role in metabolic regulation. Beyond static measures of content, the relative rates of interconversion among acyl intermediates are more closely linked to dynamic processes of physiological function in normal and diseased hearts, with the potential for both adaptive and maladaptive contributions. Indeed, multiple inefficiencies in cardiac metabolism have been identified in the decompensated, hypertrophied and failing heart. Among the intracellular responses to physiological, metabolic and pathological stresses, TAG plays a central role in the balance of lipid handling and signaling mechanisms. TAG dynamics are profoundly altered from normal in both diabetic and pathologically stressed hearts. More than just expansion or contraction of the stored lipid pool, the turnover rates of TAG are sensitive to and compete against other enzymatic pathways, anabolic and catabolic, for reactive acyl-CoA units. The rates of TAG synthesis and lipolysis thusly affect multiple components of cardiomyocyte function, including energy metabolism, cell signaling, and enzyme activation, as well as the regulation of gene expression in both normal and diseased states. This review examines the multiple etiologies and metabolic consequences of the failing heart and the central role of lipid storage dynamics in the pathogenic process. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 26993584 TI - Mitochondrial potassium homeostasis: a central player in cardioprotection. PMID- 26993586 TI - [Pseudosarcomatous chorangioma: A macroscopic and microscopic atypical tumor]. AB - We report a case of an unusual chorangioma in a 26-year-old gravida 2, para 1 female. The clinical course was complicated by premature birth at 34 weeks' gestation. The baby presented with congenital cardiac and renal malformations. The tumor was 11 cm in size, separated from the main placental mass and exhibited atypical histologic characteristics such as fibromatous areas, high cellularity, nuclear atypia and high mitotic index. These histologic features must not be interpreted as malignancy. PMID- 26993585 TI - Trajectories of limitations in activities of daily living among older adults in Mexico, 2001-2012. AB - BACKGROUND: Trajectories of disability are an essential component to understand the burden of disability at the societal level. Longitudinal studies, compared to cross-national studies, enable a better analysis of the progression of physical limitations among the elderly. However, information on disability dynamics in developing countries is limited. OBJECTIVES: This paper examines the changes in activities of daily living (ADLs) in an 11-yr. period in the Mexican elderly population aged 60 or older and identifies how sociodemographic variables alter these trajectories. METHODS: The data come from the Mexican Health and Aging Study (MHAS), a national sample of adults born in 1951 or earlier, including a baseline survey in 2001 and follow-ups in 2003 and 2012. RESULTS: The ADL score increased on average by 0.03 for every year respondents aged after 60. In contrast, the ADL score was reduced by 0.06 for every additional year of education. CONCLUSIONS: Age, gender, and years of education were confirmed to influence the trajectories of ADL limitations. Understanding the patterns of deterioration of functional limitations will help public health policies to better serve the population. PMID- 26993588 TI - [A confusing swelling of the buccal mucosa]. PMID- 26993587 TI - [Metastasis revealing malignant peritoneum mesothelioma: About the difficulty to identify the primary tumors]. AB - Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno histochemical mesothelioma markers. PMID- 26993589 TI - Endoscope-assisted medial sural artery perforator flap for head and neck reconstruction. AB - BACKGROUND: Head and neck defect reconstructions with various free perforator flaps have been widely reported. We recommend a technique of using endoscopy to confirm the location of the medial sural artery perforator (MSAP). Further, we use a free MSAP flap for the reconstruction of head and neck defects. PATIENTS AND METHODS: Since 2010, we have carried out 18 transfers of the free MSAP flap in various anatomical locations of the head and neck. The free flap was designed based on endoscopy confirmation and contained perforator vessels. The donor site was directly sutured or skin grafted. RESULTS: Twenty perforators (35.7%) detected by Doppler were confirmed by endoscopy. The number of sizable perforators ranged from one to three (mean, 1.4). The size of the flaps ranged from 22 to 88 cm(2) (mean, 41 cm(2)). The length of vascular pedicle ranged from 5 to 14 cm (mean, 8.3 cm). All 18 flaps survived with good quality and aesthetic contours. CONCLUSIONS: The MSAP flap is an ideal flap for head and neck reconstruction. It has generally thin and pliable skin, a long and reliable vascular pedicle, straightforward intramuscular dissection, the possibility of chimeric flap design, and minimal donor-site morbidity. The reliability and safety of harvesting an MSAP flap may be increased by endoscopic confirmation of the perforators. PMID- 26993590 TI - New Editor-in-Chief Introductory Comments. PMID- 26993579 TI - Fuel availability and fate in cardiac metabolism: A tale of two substrates. AB - The heart's extraordinary metabolic flexibility allows it to adapt to normal changes in physiology in order to preserve its function. Alterations in the metabolic profile of the heart have also been attributed to pathological conditions such as ischemia and hypertrophy; however, research during the past decade has established that cardiac metabolic adaptations can precede the onset of pathologies. It is therefore critical to understand how changes in cardiac substrate availability and use trigger events that ultimately result in heart dysfunction. This review examines the mechanisms by which the heart obtains fuels from the circulation or from mobilization of intracellular stores. We next describe experimental models that exhibit either an increase in glucose use or a decrease in FA oxidation, and how these aberrant conditions affect cardiac metabolism and function. Finally, we highlight the importance of alternative, relatively under-investigated strategies for the treatment of heart failure. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 26993591 TI - Generation of a Xenopus laevis F1 albino J strain by genome editing and oocyte host-transfer. AB - Completion of the Xenopus laevis genome sequence from inbred J strain animals has facilitated the generation of germline mutant X. laevis using targeted genome editing. In the last few years, numerous reports have demonstrated that TALENs are able to induce mutations in F0 Xenopus embryos, but none has demonstrated germline transmission of such mutations in X. laevis. In this report we used the oocyte host-transfer method to generate mutations in both tyrosinase homeologs and found highly-penetrant germline mutations; in contrast, embryonic injections yielded few germline mutations. We also compared the distribution of mutations in several F0 somatic tissues and germ cells and found that the majority of mutations in each tissue were different. These results establish that X. laevis J strain animals are very useful for generating germline mutations and that the oocyte host-transfer method is an efficient technique for generating mutations in both homeologs. PMID- 26993592 TI - Application of a Hybrid Vascular Graft for Rapid Endoluminal Branch Anastomoses During Open Aortic Reconstruction. AB - The treatment of thoracoabdominal aneurysms and juxtarenal aortic aneurysms remains technically challenging, with outcomes primarily dictated by aortic cross clamp and end-organ ischemia during branch reconstruction. This has remained a challenge for the surgeon regardless of an elective setting or an emergent operation. Here we describe the application of a novel hybrid graft technique for aortic branch reconstruction using rapid, endoluminal anastomoses during open aortic reconstruction. PMID- 26993593 TI - Abdominal Aortic Pseudoaneurysm Caused by a Delayed Lumbar Puncture-Related Complication. PMID- 26993594 TI - Distal Embolization During Percutaneous Subclavian Artery Intervention. AB - Distal embolization due to atherothrombotic debris during subclavian artery interventions is extremely rare and can usually be managed conservatively. Herein, we describe a case of acute hand ischemia due to massive distal embolization during balloon angioplasty and stenting of a left subclavian artery chronic total occlusion. This limb-threatening complication was effectively treated with rescue surgical thrombectomy. PMID- 26993596 TI - Synapsin III in brain development. PMID- 26993595 TI - Alterations of tumor microenvironment by carbon monoxide impedes lung cancer growth. AB - We hypothesized that tumor-associated macrophages (TAMs) are controlled by the diffusible gas carbon monoxide (CO). We demonstrate that induction of apoptosis in lung tumors treated with low doses of CO is associated with increased CD86 expression and activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (Erk) 1/2 pathway in tumor microenvironment. Presence of CD86-positive cells was required for the anti tumoral effects of CO in established A549 xenografts. We show that the effects of CO on tumor stroma and reprogramming of macrophages towards the anti-tumoral phenotype is mediated by reactive oxygen species (ROS)-dependent activation of MAPK/Erk1/2-c-myc pathway as well as Notch 1-dependent negative feedback on the metabolic enzyme heme oxygenase-1 (HO-1). We find a similar negative correlation between HO-1 and active MAPK-Erk1/2 levels in human lung cancer specimens.In summary, we describe novel non-cell autonomous mechanisms by which the diffusible gas CO dictates changes in the tumor microenvironment through the modulation of macrophages. PMID- 26993597 TI - Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection. AB - Renal cell carcinoma (RCC) is frequently diagnosed at advanced stages of disease, although early diagnosis has much favorable prognosis. This study assessed aberrant expression of cytosolic carboxypeptidase 6 (CCP6) leading to accumulation of serum polyglutamylated DNAJC7 as a biomarker for early RCC detection. A total of 835 RCCs, 143 chronic nephritis, 170 kidney stones and 415 health controls were collected for qRT-PCR, immunohistochemistry and Western blot analysis of CCP6 expression and mass spectrometry of DNAJC7 and polyglutamylated DNAJC7. The data showed that CCP6 expression was significantly decreased in 30 RCC tissues and that mass spectrometric and pull-down analysis identified DNAJC7 as a substrate of CCP6 and showed upregulated polyglutamylated-DNAJC7 (polyE DNAJC7) in sera of RCC patients. The electrochemiluminescence immunoassay of large-scale serum samples from multi-institutes further confirmed the remarkable increase of polyE-DNAJC7 in 805 RCCs compared to that of 385 healthy controls (p < 0.001), 128 patients with chronic nephritis (p < 0.001), and 153 with kidney stone (p < 0.001). Serum level of DNAJC7-polyE protein was also associated with advanced RCC stage and grade in 805 patients. The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for RCC early detection and association with advanced tumor stages and grade, which provides support of further polyglutamylation research in RCC. PMID- 26993598 TI - Systematic large-scale meta-analysis identifies a panel of two mRNAs as blood biomarkers for colorectal cancer detection. AB - Colorectal cancer (CRC) is the third most common cancer in the world. A significant survival rate is achieved if it is detected at an early stage. A whole blood screening test, without any attempt to isolate blood fractions, could be an important tool to improve early detection of colorectal cancer. We searched for candidate markers with a novel approach based on the Transcriptome Mapper (TRAM), aimed at identifying specific RNAs with the highest differential expression ratio between colorectal cancer tissue and normal blood samples. This tool permits a large-scale systematic meta-analysis of all available data obtained by microarray experiments. The targeting of RNA took into consideration that tumour phenotypic variation is associated with changes in the mRNA levels of genes regulating or affecting this variation.A real time quantitative reverse transcription polymerase chain reaction (qRT- PCR) was applied to the validation of candidate markers in the blood of 67 patients and 67 healthy controls. The expression of genes: TSPAN8, LGALS4, COL1A2 and CEACAM6 resulted as being statistically different.In particular ROC curves attested for TSPAN8 an AUC of 0.751 with a sensitivity of 83.6% and a specificity of 58.2% at a cut off of 10.85, while the panel of the two best genes showed an AUC of 0.861 and a sensitivity of 92.5% with a specificity of 67.2%.Our preliminary study on a total of 134 subjects showed promising results for a blood screening test to be validated in a larger cohort with the staging stratification and in patients with other gastrointestinal diseases. PMID- 26993599 TI - Cell fate determination in cisplatin resistance and chemosensitization. AB - Understanding the determination of cell fate choices after cancer treatment will shed new light on cancer resistance. In this study, we quantitatively analyzed the individual cell fate choice in resistant UM-SCC-38 head and neck cancer cells exposed to cisplatin. Our study revealed a highly heterogeneous pattern of cell fate choices in UM-SCC-38 cells, in comparison to that of the control, non tumorigenic keratinocyte HaCaT cells. In both UM-SCC-38 and HaCaT cell lines, the majority of cell death occurred during the immediate interphase without mitotic entry, whereas significant portions of UM-SCC-38 cells survived the treatment via either checkpoint arrest or checkpoint slippage. Interestingly, checkpoint slippage occurred predominantly in cells treated in late S and G2 phases, and cells in M-phase were hypersensitive to cisplatin. Moreover, although the cisplatin-resistant progression of mitosis exhibited no delay in general, prolonged mitosis was correlated with the induction of cell death in mitosis. The finding thus suggested a combinatorial treatment using cisplatin and an agent that blocks mitotic exit. Consistently, we showed a strong synergy between cisplatin and the proteasome inhibitor Mg132. Finally, targeting the DNA damage checkpoint using inhibitors of ATR, but not ATM, effectively sensitized UM-SCC-38 to cisplatin treatment. Surprisingly, checkpoint targeting eliminated both checkpoint arrest and checkpoint slippage, and augmented the induction of cell death in interphase without mitotic entry. Taken together, our study, by profiling cell fate determination after cisplatin treatment, reveals new insights into chemoresistance and suggests combinatorial strategies that potentially overcome cancer resistance. PMID- 26993600 TI - Tumor growth suppressive effect of IL-4 through p21-mediated activation of STAT6 in IL-4Ralpha overexpressed melanoma models. AB - To evaluate the significance of interleukin 4 (IL-4) in tumor development, we compared B16F10 melanoma growth in IL-4-overespressing transgenic mice (IL-4 mice) and non-transgenic mice. In IL-4 mice, reduced tumor volume and weight were observed when compared with those of non-transgenic mice. Significant activation of DNA binding activity of STAT6, phosphorylation of STAT6 as well as IL-4, IL 4Ralpha and p21 expression were found in the tumor tissues of IL-4 mice compared to non-transgenic mice. Higher expression of IL-4, STAT6 and p21 in human melanoma tissue compared to normal human skin tissue was also found. Higher expression of apoptotic protein such as cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, p53 and p21, but lower expression levels of survival protein such as Bcl-2 were found in the tumor of IL-4 mice. In vitro study, we found that overexpression of IL-4 significantly inhibited SK-MEL-28 human melanoma cell and B16F10 murine melanoma cell growth via p21-mediated activation of STAT6 pathway as well as increased expression of apoptotic cell death proteins. Moreover, p21 knockdown with siRNA abolished IL-4 induced activation of STAT6 and expression of p53 and p21 accompanied with reduced IL-4 expression as well as melanoma cell growth inhibition. Therefore, these results showed that IL 4 overexpression suppressed tumor development through p21-mediated activation of STAT6 pathways in melanoma models. PMID- 26993602 TI - Transmembrane adaptor protein PAG1 is a novel tumor suppressor in neuroblastoma. AB - Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with high mortality rates. The tyrosine kinase c-Src has been known to play an important role in differentiation of NB cells, but the mechanism of c-Src regulation has not been defined. Here, we characterize PAG1 (Cbp, Csk binding protein), a central inhibitor of c-Src and other Src family kinases, as a novel tumor suppressor in NB. Clinical cohort analysis demonstrate that low expression of PAG1 is a significant prognostic factor for high stage disease, increased relapse, and worse overall survival for children with NB. PAG1 knockdown in NB cells promotes proliferation and anchorage-independent colony formation with increased activation of AKT and ERK downstream of c-Src, while PAG1 overexpression significantly rescues these effects. In vivo, PAG1 overexpression significantly inhibits NB tumorigenicity in an orthotopic xenograft model. Our results establish PAG1 as a potent tumor suppressor in NB by inhibiting c-Src and downstream effector pathways. Thus, reactivation of PAG1 and inhibition of c-Src kinase activity represents an important novel therapeutic approach for high-risk NB. PMID- 26993601 TI - Role of ADAM17 in invasion and migration of CD133-expressing liver cancer stem cells after irradiation. AB - We investigated the biological role of CD133-expressing liver cancer stem cells (CSCs) enriched after irradiation of Huh7 cells in cell invasion and migration. We also explored whether a disintegrin and metalloproteinase-17 (ADAM17) influences the metastatic potential of CSC-enriched hepatocellular carcinoma (HCC) cells after irradiation. A CD133-expressing Huh7 cell subpopulation showed greater resistance to sublethal irradiation and specifically enhanced cell invasion and migration capabilities. We also demonstrated that the radiation induced MMP-2 and MMP-9 enzyme activities as well as the secretion of vascular endothelial growth factor were increased more predominantly in Huh7CD133+ cell subpopulations than Huh7CD133- cell subpopulations. Furthermore, we showed that silencing ADAM17 significantly inhibited the migration and invasiveness of enriched Huh7CD133+ cells after irradiation; moreover, Notch signaling was significantly reduced in irradiated CD133-expressing liver CSCs following stable knockdown of the ADAM17 gene. In conclusion, our findings indicate that CD133 expressing liver CSCs have considerable metastatic capabilities after irradiation of HCC cells, and their metastatic capabilities might be maintained by ADAM17. Therefore, suppression of ADAM17 shows promise for improving the efficiency of current radiotherapies and reducing the metastatic potential of liver CSCs during HCC treatment. PMID- 26993603 TI - GP73 N-glycosylation at Asn144 reduces hepatocellular carcinoma cell motility and invasiveness. AB - Golgi Protein 73 (GP73) is a potential liver disease glycobiomarker warranting comprehensive analyses of its glycan structure and glycosylation function. In this study, we used mass spectrometry to identify glycosylation sites and the glycan structure, high-throughput lectin microarray to provide rapid and sensitive profiling of glycoconjugates, and site-directed mutagenesis to clarify the impact of glycans on target glycoproteins in vivo. We identified three GP73 N glycosylation sites: Asn109, Asn144 and Asn398. We found five glycoforms on Asn144, including biantennary, triantennary and fucosylated glycans. Removal of N glycans at Asn144 enhanced the motility and invasiveness of hepatocellular carcinoma cells, possibly due to inhibition of cell adhesion related to the changes of cell membrane glycosylation. This study increases our understanding of the functional relevance of GP73 glycosylation and suggests that Asn144-deleted GP73 can influence the progression and metastasis of hepatocellular carcinoma. PMID- 26993604 TI - Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells. AB - Expression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects. PMID- 26993605 TI - Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay. AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Here, we applied a high throughput serum peptidome analysis to identify circulating peptide markers of ESCC. Weak cationic exchange magnetic beads coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for two-stage proteotypic peptide profiling in complex serum samples collected from 477 cancer patients and healthy controls. We established a genetic algorithm model containing three significantly differentially expressed peptides at 1,925.5, 2,950.6 and 5,900.0 Da with a sensitivity and specificity of 97.00% and 95.92% in the training set and 97.03% and 100.00% in the validation set, respectively. The model's diagnostic capability was significantly better than SCC-Ag and Cyfra 21 1, especially for early stage ESCC, with an achieved sensitivity of 96.94%. Subsequently, these peptides were identified as fragments of AHSG, TSP1 and FGA by linear ion trap-orbitrap hybrid tandem mass spectrometry. Notably, increased tissue and serum levels of TSP1 in ESCC were verified and correlated with disease progression. In addition, tissue TSP1 was an independent poor prognostic factor in ESCC. In conclusion, the newly established circulating peptide panel and identified proteins could serve as potential biomarkers for the early detection and diagnosis of ESCC. Nevertheless, a larger cohort will be required for further unequivocal validation of their clinical application. PMID- 26993606 TI - Inactivation of RASA1 promotes melanoma tumorigenesis via R-Ras activation. AB - Inactivation of Ras GTPase activating proteins (RasGAPs) can activate Ras, increasing the risk for tumor development. Utilizing a melanoma whole genome sequencing (WGS) data from 13 patients, we identified two novel, clustered somatic missense mutations (Y472H and L481F) in RASA1 (RAS p21 protein activator 1, also called p120RasGAP). We have shown that wild type RASA1, but not identified mutants, suppresses soft agar colony formation and tumor growth of BRAF mutated melanoma cell lines via its RasGAP activity toward R-Ras (related RAS viral (r-ras) oncogene homolog) isoform. Moreover, R-Ras increased and RASA1 suppressed Ral-A activation among Ras downstream effectors. In addition to mutations, loss of RASA1 expression was frequently observed in metastatic melanoma samples on melanoma tissue microarray (TMA) and a low level of RASA1 mRNA expression was associated with decreased overall survival in melanoma patients with BRAF mutations. Thus, these data support that RASA1 is inactivated by mutation or by suppressed expression in melanoma and that RASA1 plays a tumor suppressive role by inhibiting R-Ras, a previously less appreciated member of the Ras small GTPases. PMID- 26993607 TI - The comparison of outcomes from tyrosine kinase inhibitor monotherapy in second- or third-line for advanced non-small-cell lung cancer patients with wild-type or unknown EGFR status. AB - BACKGROUND: Second-line treatment for advanced non-small-cell lung cancer (NSCLC) patients includes monotherapy with a third-generation cytotoxic drug (CT) or a tyrosine kinase inhibitor (TKI). These options are the actual standard for EGFR wild-type (WT) status, as patients with EGFR mutations achieve greater benefit by the use of TKI in first-line treatment. Some clinical trials and meta-analyses investigated the comparison between CT and TKI in second-line, but data are conflicting. METHODS: We designed a retrospective trial to gather information about TKI sensitivity in comparison with CT. We selected from clinical records patients treated with at least 1 line of CT and at least 1 line of TKI. We collected data about age, sex, performance status, comorbidity, smoking status, histotype, metastatic sites, EGFR status, treatment schedule, better response and time-to-progression (TTP) for each line of treatment and overall survival (OS). RESULTS: 93 patients met selection criteria. Mean age 66,7 (range: 46-84). M/F ratio is 3:1. 39 EGFR-WT and 54 EGFR-UK. All patients received erlotinib or gefitinib as second-line treatment or erlotinib as third-line treatment. No TTP differences were observed for both second-line (HR:0,91; p = 0,6333) and third line (HR:1.1; p = 0,6951) treatment (TKI vs CT). A trend of a benefit in OS in favor of 3rd-line TKI (HR:0,68; p = 0,11). CONCLUSIONS: This study explores the role of TKIs in EGFR non-mutated NSCLC patients. OS analysis highlights a trend to a benefit in patients who received TKI in third-line, even if this result is statistically non-significant. Further analysis are needed to find an explanation for this observation. PMID- 26993608 TI - Post-translational modification-regulated leukocyte adhesion and migration. AB - Leukocytes undergo frequent phenotypic changes and rapidly infiltrate peripheral and lymphoid tissues in order to carry out immune responses. The recruitment of circulating leukocytes into inflamed tissues depends on integrin-mediated tethering and rolling of these cells on the vascular endothelium, followed by transmigration into the tissues. This dynamic process of migration requires the coordination of large numbers of cytosolic and transmembrane proteins whose functional activities are typically regulated by post-translational modifications (PTMs). Our recent studies have shown that the lysine methyltransferase, Ezh2, critically regulates integrin signalling and governs the adhesion dynamics of leukocytes via direct methylation of talin, a key molecule that controls these processes by linking integrins to the actin cytoskeleton. In this review, we will discuss the various modes of leukocyte migration and examine how PTMs of cytoskeletal/adhesion associated proteins play fundamental roles in the dynamic regulation of leukocyte migration. Furthermore, we will discuss molecular details of the adhesion dynamics controlled by Ezh2-mediated talin methylation and the potential implications of this novel regulatory mechanism for leukocyte migration, immune responses, and pathogenic processes, such as allergic contact dermatitis and tumorigenesis. PMID- 26993609 TI - Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer. AB - Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALK-positive NSCLC patients (3-15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0-2 cells/1.88 mL of blood). The latter range was validated as the 'false positive' cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing. PMID- 26993611 TI - Identification of a novel miR-146a from Pinctada martensii involved in the regulation of the inflammatory response. AB - Increasing evidence demonstrated that microRNAs (miRNAs) play critical roles in innate immunity in vertebrates and invertebrates. MiR-146a/b is reported as a key regulator of the immune response through mediating Toll-like receptor and cytokine signalling. In this study, a novel miR-146a was identified and characterised from Pinctada martensii (designated as pm-miR-146a), and its roles in modulating the inflammatory response after LPS stimulation were also investigated. Pm-miR-146a ubiquitously expressed in all examined tissues, with the highest level in the mantle and lowest expression in the haemolymph. Pm-miR 146a increased at 24 h after lipoplysaccharide injection, in union with up regulated NF-kappaB (P < 0.05). The over-expression of pm-miR-146a in vivo could significantly inhibit the expression of macrophage migration inhibitory factor (MIF), the potential target gene predicted by miRanda, while enforcing pm-miR 146a involved in the down-regulation of NF-kappaB. Thus, we propose that pm-miR 146a plays a role of negative feedback regulation to the NF-kappaB signal by repressing the expression of the pro-inflammatory cytokine MIF. These findings revealed that miR-146a represents a critical role in inflammatory response and offers new evidence for miRNAs in the innate immunity of molluscs. PMID- 26993612 TI - Molecular characterization of an inhibitor of NF-kappaB in the scallop Argopecten purpuratus: First insights into its role on antimicrobial peptide regulation in a mollusk. AB - Inhibitors of nuclear factor kappa B (IkappaBs) are major control components of the Rel/NF-kappaB signaling pathway, a key regulator in the modulation of the expression of immune-related genes in vertebrates and invertebrates. The activation of the Rel/NF-kappaB signaling pathway depends largely in the degradation of IkappaB proteins and thus, IkappaBs are a main target for the identification of genes whose expression is controlled by Rel/NF-kappaB pathway. In order to identify such regulation in bivalve mollusks, the cDNA sequence encoding an IkappaB protein was characterized in the scallop Argopecten purpuratus, ApIkappaB. The cDNA sequence of ApIkappaB is comprised of 1480 nucleotides with a 1086 bp open reading frame encoding for 362 amino acids. Bioinformatics analysis showed that ApIkappaB displays the conserved features of IkappaB proteins. The deduced amino acid sequence consists of a 39.7 kDa protein, which has an N-terminal degradation motif, six ankyrin repeats and a C-terminal phosphorylation site motif. Phylogenetic analysis revealed a high degree of identity between ApIkappaB and other IkappaBs from mollusks, but also to arthropod cactus proteins and vertebrate IkappaBs. Tissue expression analysis indicated that ApIkappaB is expressed in all examined tissues and it is upregulated in circulating hemocytes from scallops challenged with the pathogenic Gram-negative bacterium Vibrio splendidus. After inhibiting ApIkappaB gene expression using the RNA interference technology, the gene expression of the antimicrobial peptide big defensin was upregulated in hemocytes from non challenged scallops. Results suggest that ApIkappaB may control the expression of antimicrobial effectors such as big defensin via a putative Rel/NF-kappaB signaling pathway. This first evidence will help to deepen the knowledge of the Rel/NF-kappaB conserved pathway in scallops. PMID- 26993613 TI - Expression profile of carp IFN correlate with the up-regulation of interferon regulatory factor-1 (IRF-1) in vivo and in vitro: the pivotal molecules in antiviral defense. AB - Interferon regulatory factors (IRFs) are a family of transcription factors that mediate the transcriptional regulation of interferon (IFN) genes and IFN inducible genes. In this study, IRF-1 gene is cloned from the common carp, Cyprinus carpio L., named CcIRF-1. The full-length cDNA of CcIRF-1 is 1427 bp, including an open reading frame of 861 bp encoding a protein of 286 amino acids. The putative CcIRF-1 is characterized by a conserved DNA-binding domain and includes a signature of six conserved tryptophan residues. The genomic sequence of CcIRF-1 is described, which consists of 9 exons and 8 introns. The sequence analysis shows that CcIRF-1 is clustered into IRF-1 subfamily, and has the closest relationship with the zebrafish IRF-1. CcIRF-1 is found constitutively expressed in different organs of healthy common carp. The main findings are that CcIRF-1 is up-regulated following stimulation with poly(I:C) in all tested tissues. Moreover, the downstream gene of IRF-1 - IFN is found to be correlated with the up-regulation of IRF-1 after injection with poly(I:C). Furthermore, we also isolate the peripheral blood leukocytes (PBLs) and find that there is a relevance between the expression profile of CcIRF-1 and IFN in poly(I:C) stimulated PBLs. PMID- 26993610 TI - Meta-analysis of transcriptome data identifies a novel 5-gene pancreatic adenocarcinoma classifier. AB - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is largely incurable due to late diagnosis. Superior early detection biomarkers are critical to improving PDAC survival and risk stratification. EXPERIMENTAL DESIGN: Optimized meta-analysis of PDAC transcriptome datasets identified and validated key PDAC biomarkers. PDAC specific expression of a 5-gene biomarker panel was measured by qRT-PCR in microdissected patient-derived FFPE tissues. Cell-based assays assessed impact of two of these biomarkers, TMPRSS4 and ECT2, on PDAC cells. RESULTS: A 5-gene PDAC classifier (TMPRSS4, AHNAK2, POSTN, ECT2, SERPINB5) achieved on average 95% sensitivity and 89% specificity in discriminating PDAC from non-tumor samples in four training sets and similar performance (sensitivity = 94%, specificity = 89.6%) in five independent validation datasets. This classifier accurately discriminated PDAC from chronic pancreatitis (AUC = 0.83), other cancers (AUC = 0.89), and non-tumor from PDAC precursors (AUC = 0.92) in three independent datasets. Importantly, the classifier distinguished PanIN from healthy pancreas in the PDX1-Cre;LSL-KrasG12D PDAC mouse model. Discriminatory expression of the PDAC classifier genes was confirmed in microdissected FFPE samples of PDAC and matched surrounding non-tumor pancreas or pancreatitis. Notably, knock-down of TMPRSS4 and ECT2 reduced PDAC soft agar growth and cell viability and TMPRSS4 knockdown also blocked PDAC migration and invasion. CONCLUSIONS: This study identified and validated a highly accurate 5-gene PDAC classifier for discriminating PDAC and early precursor lesions from non-malignant tissue that may facilitate early diagnosis and risk stratification upon validation in prospective clinical trials. Cell-based experiments of two overexpressed proteins encoded by the panel, TMPRSS4 and ECT2, suggest a causal link to PDAC development and progression, confirming them as potential therapeutic targets. PMID- 26993614 TI - Innate immune-stimulating and immune genes up-regulating activities of three types of alginate from Sargassum siliquosum in Pacific white shrimp, Litopenaeus vannamei. AB - The Total Haemocyte Count (THC), phenoloxidase (PO), Superoxide Dismutase (SOD) activity, Phagocytic Activity/Index and Total Protein Plasma (TPP) were examined after feeding the white shrimp Litopenaeus vannamei with diets supplemented with three different types of alginates (acid, calcium and sodium alginates). Immune related genes expression was evaluated by quantitative Real Time PCR (qRT-PCR). Results indicated that the immune parameters directly increased according to the doses of alginates and time. The 2.0 g kg(-1) of acid and sodium alginate treatments were gave better results. Four immune-related genes expression i.e. LGBP, Toll, Lectin, proPO were up regulated. It is therefore concluded that the supplementation of alginate of Sargassum siliquosum on the diet of L. vannamei enhanced the innate immunity as well as the expression of immune-related genes. It is the first report on the simultaneous evaluation of three alginate types to enhance innate immune parameters and immune-related genes expression in L. vannamei. PMID- 26993615 TI - Cardiac MRI based numerical modeling of left ventricular fluid dynamics with mitral valve incorporated. AB - Recent numerical studies were focused on the modeling of flow in patient-specific left ventricle (LV); however, the mitral valve (MV) was usually excluded. In this study, both patient-specific LV and MV were modeled to achieve a more realistic intraventricular flow. Cardiac MRI images were acquired from a pulmonary arterial hypertension (PAH) patient and a healthy volunteer, and manual segmentation was conducted to reconstruct three-dimensional (3D) LV and MV geometries at each frame. Based on these 3D geometries, vortex formation time (VFT) was derived, and the values were 4.0 and 6.5 for the normal subject and the PAH patient, respectively. Based on studies in the literature, VTF in the healthy subject fell within the normal range, while that in the PAH patient exceeded the threshold for normality. The vortex structures in the LV clearly showed that the vortex ring was initiated from the tips of the MV instead of the mitral annulus. The excessive VFT during the rapid filling phase in the PAH patient resulted in a trailing flow structure behind the primary vortex ring, which was not observed in the normal subject. It can be deduced from this study that incorporating the MV into a patient-specific model is necessary to produce more reasonable VFT and intraventricular flow. PMID- 26993616 TI - Light therapy in the treatment of patients with bipolar depression: A meta analytic study. AB - Light therapy (LT) has been widely used in the treatment of seasonal affective disorder. Recently some evidence indicated that LT may play a role in bipolar depression, either as monotherapy or in combination with total sleep deprivation (TSD). However, the studies examining the treatment effect of LT in bipolar depression resulted in inconsistent findings. To clarify the role of LT in the disorder, we conducted a meta-analysis to compare the efficacy of LT in the treatment of bipolar depression. The results of individual studies were synthesized by a random effects model. Nine studies including 489 patients with bipolar depression were included in this current meta-analysis. We found that disease severity was significantly decreased after LT, in both with and without TSD, and with concomitant medication (p<0.001). Augmentation treatment with LT significantly decreased disease severity compared to treatment without LT (p=0.024). Our results highlight the significant efficacy of LT, either as monotherapy or in combination with TSD, in the treatment of bipolar depression. However, the detailed mechanism of LT still remains elusive. Further well designed controlled trials are required to investigate the optimal intensity and frequency of LT in the treatment of bipolar depression. PMID- 26993617 TI - The Cytoplasmic Carbonic Anhydrases betaCA2 and betaCA4 Are Required for Optimal Plant Growth at Low CO2. AB - Carbonic anhydrases (CAs) are zinc metalloenzymes that interconvert CO2 and HCO3 (-) In plants, both alpha- and beta-type CAs are present. We hypothesize that cytoplasmic betaCAs are required to modulate inorganic carbon forms needed in leaf cells for carbon-requiring reactions such as photosynthesis and amino acid biosynthesis. In this report, we present evidence that betaCA2 and betaCA4 are the two most abundant cytoplasmic CAs in Arabidopsis (Arabidopsis thaliana) leaves. Previously, betaCA4 was reported to be localized to the plasma membrane, but here, we show that two forms of betaCA4 are expressed in a tissue-specific manner and that the two proteins encoded by betaCA4 localize to two different regions of the cell. Comparing transfer DNA knockout lines with wild-type plants, there was no reduction in the growth rates of the single mutants, betaca2 and betaca4 However, the growth rate of the double mutant, betaca2betaca4, was reduced significantly when grown at 200 MUL L(-1) CO2 The reduction in growth of the double mutant was not linked to a reduction in photosynthetic rate. The amino acid content of leaves from the double mutant showed marked reduction in aspartate when compared with the wild type and the single mutants. This suggests the cytoplasmic CAs play an important but not previously appreciated role in amino acid biosynthesis. PMID- 26993619 TI - Transcription profile of Trichophyton rubrum conidia grown on keratin reveals the induction of an adhesin-like protein gene with a tandem repeat pattern. AB - BACKGROUND: Trichophyton rubrum is a cosmopolitan filamentous fungus that can infect human keratinized tissue (skin, nails and, rarely, hair) and is the major agent of all chronic and recurrent dermatophytoses. The dermatophyte infection process is initiated through the release of arthroconidial adhesin, which binds to the host stratum corneum. The conidia then germinate, and fungal hyphae invade keratinized skin structures through the secretion of proteases. Although arthroconidia play a central role in pathogenesis, little is known about the dormancy and germination of T. rubrum conidia and the initiation of infection. The objective of this study was to evaluate the transcriptional gene expression profile of T. rubrum conidia during growth on keratin- or elastin-containing medium, mimicking superficial and deep dermatophytosis, respectively. RESULTS: A transcriptional profiling analysis was conducted using a custom oligonucleotide based microarray by comparing T. rubrum conidia grown on elastin and keratin substrates. This comparison shows differences according to protein source used, but consisted of a very small set of genes, which could be attributed to the quiescent status of conidia. The modulated genes were related to the dormancy, survival and germination of conidia, including genes involved in the respiratory chain, signal transduction and lipid metabolism. However, an induction of a great number of proteases occurred when T. rubrum was grown in the presence of keratin such as the subtilisin family of proteases (Sub 1 and Sub 3) and leucine aminopeptidase (Lap 1 and Lap 2). Interestingly, keratin also promoted the up regulation of a gene encoding an adhesin-like protein with a tandem repeat sequence. In silico analysis showed that the protein contains a domain related to adhesin that may play a role in host-pathogen interactions. The expression of this adhesin-like gene was also induced during the co-culture of T. rubrum with a human keratinocyte cell line, confirming its role in fungal-host interactions. CONCLUSION: These results contribute to the discovery of new targets involved in the adhesion of conidia and the maintenance of conidial dormancy, which are essential for triggering the process of infection and the chronicity of dermatophytosis. PMID- 26993618 TI - Glucosylation of 4-Hydroxy-2,5-Dimethyl-3(2H)-Furanone, the Key Strawberry Flavor Compound in Strawberry Fruit. AB - Strawberries emit hundreds of different volatiles, but only a dozen, including the key compound HDMF [4-hydroxy-2,5-dimethyl-3(2H)-furanone] contribute to the flavor of the fruit. However, during ripening, a considerable amount of HDMF is metabolized to the flavorless HDMF beta-d-glucoside. Here, we functionally characterize nine ripening-related UGTs (UDP-glucosyltransferases) in Fragaria that function in the glucosylation of volatile metabolites by comprehensive biochemical analyses. Some UGTs showed a rather broad substrate tolerance and glucosylated a range of aroma compounds in vitro, whereas others had a more limited substrate spectrum. The allelic UGT71K3a and b proteins and to a lesser extent UGT73B24, UGT71W2, and UGT73B23 catalyzed the glucosylation of HDMF and its structural homolog 2(or 5)-ethyl-4-hydroxy-5(or 2)-methyl-3(2H)-furanone. Site-directed mutagenesis to introduce single K458R, D445E, D343E, and V383A mutations and a double G433A/I434V mutation led to enhanced HDMF glucosylation activity compared to the wild-type enzymes. In contrast, a single mutation in the center of the plant secondary product glycosyltransferase box (A389V) reduced the enzymatic activity. Down-regulation of UGT71K3 transcript expression in strawberry receptacles led to a significant reduction in the level of HDMF glucoside and a smaller decline in HDMF-glucoside-malonate compared with the level in control fruits. These results provide the foundation for improvement of strawberry flavor and the biotechnological production of HDMF-glucoside. PMID- 26993620 TI - Characterisation of the epidemic strain of H3N8 equine influenza virus responsible for outbreaks in South America in 2012. AB - BACKGROUND: An extensive outbreak of equine influenza occurred across multiple countries in South America during 2012. The epidemic was first reported in Chile then spread to Brazil, Uruguay and Argentina, where both vaccinated and unvaccinated animals were affected. In Brazil, infections were widespread within 3months of the first reported cases. Affected horses included animals vaccinated with outdated vaccine antigens, but also with the OIE-recommended Florida clade 1 strain South Africa/4/03. METHODS: Equine influenza virus strains from infected horses were isolated in eggs, then a representative strain was subjected to full genome sequencing using segment-specific primers with M13 tags. Phylogenetic analyses of nucleotide sequences were completed using PhyML. Amino acid sequences of haemagglutinin and neuraminidase were compared against those of vaccine strains and recent isolates from America and Uruguay, substitutions were mapped onto 3D protein structures using PyMol. Antigenic analyses were completed by haemagglutination-inhibition assay using post-infection ferret sera. RESULTS: Nucleotide sequences of the haemaglutinin (HA) and neuraminidase (NA) genes of Brazilian isolate A/equine/Rio Grande do Sul/2012 were very similar to those of viruses belonging to Florida clade 1 and clustered with contemporary isolates from the USA. Comparison of their amino acid sequences against the OIE recommended Florida clade 1 vaccine strain A/equine/South Africa/4/03 revealed five amino acid substitutions in HA and seven in NA. Changes in HA included one within antigenic site A and one within the 220-loop of the sialic acid receptor binding site. However, antigenic analysis by haemagglutination inhibition (HI) assay with ferret antisera raised against representatives of European, Kentucky and Florida sublineages failed to indicate any obvious differences in antigenicity. CONCLUSIONS: An extensive outbreak of equine influenza in South America during 2012 was caused by a virus belonging to Florida clade 1, closely related to strains circulating in the USA in 2011. Despite reports of vaccine breakdown with products containing the recommended strain South Africa/03, no evidence was found of significant antigenic drift. Other factors may have contributed to the rapid spread of this virus, including poor control of horse movement. PMID- 26993621 TI - Health insurance determines antenatal, delivery and postnatal care utilisation: evidence from the Ghana Demographic and Health Surveillance data. AB - OBJECTIVE: This study aims to evaluate the effect of maternal health insurance status on the utilisation of antenatal, skilled delivery and postnatal care. DESIGN: A population-based cross-sectional study. SETTING AND PARTICIPANTS: We utilised the 2008 Demographic and Health Survey data of Ghana, which included 2987 women who provided information on maternal health insurance status. PRIMARY OUTCOMES: Utilisation of antenatal, skilled delivery and postnatal care. STATISTICAL ANALYSES: Multivariable logistic regression was applied to determine the independent association between maternal health insurance and utilisation of antenatal, skilled delivery and postnatal care. RESULTS: After adjusting for socioeconomic, demographic and obstetric factors, we observed that among insured women the likelihood of having antenatal care increased by 96% (OR 1.96; 95% CI 1.52 to 2.52; p value<0.001) and of skilled delivery by 129% (OR 2.29; 95% CI 1.92 to 2.74; p value<0.001), while postnatal care among insured women increased by 61% (OR 1.61; 95% CI 1.17 to 2.21; p value<0.01). CONCLUSIONS: This study demonstrated that maternal health insurance status plays a significant role in the uptake of the maternal, neonatal and child health continuum of care service. PMID- 26993622 TI - Association between subjective social status and cardiovascular disease and cardiovascular risk factors: a systematic review and meta-analysis. AB - OBJECTIVE: To determine the association between subjective social status (SSS), or the individual's perception of his or her position in the social hierarchy, and the odds of coronary artery disease (CAD), hypertension, diabetes, obesity and dyslipidaemia. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, SocINDEX, Web of Science and reference lists of all included studies up to October 2014, with a verification search in July 2015. Inclusion criteria were original studies in adults that reported odds, risk or hazard ratios of at least one outcome of interest (CAD, hypertension, diabetes, obesity or dyslipidaemia), comparing 'lower' versus 'higher' SSS groups, where SSS is measured on a self-anchoring ladder. ORs were pooled using a random-effects model. RESULTS: 10 studies were included in the systematic review; 9 of these were included in the meta-analysis. In analyses unadjusted for objective socioeconomic status (SES) measures such as income, education or occupation, the pooled OR comparing the bottom versus the top of the SSS ladder was 1.82 (95% CI 1.10 to 2.99) for CAD, 1.88 (95% CI 1.27 to 2.79) for hypertension, 1.90 (95% CI 1.25 to 2.87) for diabetes, 3.68 (95% CI 2.03 to 6.64) for dyslipidaemia and 1.57 (95% CI 0.95 to 2.59) for obesity. These associations were attenuated when adjusting for objective SES measures, with the only statistically significant association remaining for dyslipidaemia (OR 2.10, 95% CI 1.09 to 4.06), though all ORs remained greater than 1. CONCLUSIONS: Lower SSS is associated with significantly increased odds of CAD, hypertension, diabetes and dyslipidaemia, with a trend towards increased odds of obesity. These trends are consistently present, though the effects attenuated when adjusting for SES, suggesting that perception of one's own status on a social hierarchy has health effects above and beyond one's actual income, occupation and education. PMID- 26993623 TI - Recording and treatment of premenstrual syndrome in UK general practice: a retrospective cohort study. AB - OBJECTIVES: To investigate the rate of recording of premenstrual syndrome diagnoses in UK primary care and describe pharmacological treatments initiated following a premenstrual syndrome (PMS) diagnosis. DESIGN: Retrospective cohort study. SETTING: UK primary care. PARTICIPANTS: Women registered with a practice contributing to The Health Improvement Network primary care database between 1995 and 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the rate of first premenstrual syndrome records per 1000 person years, stratified by calendar year and age. The secondary outcome was the proportions of women with a premenstrual syndrome record prescribed a selective serotonin reuptake inhibitor, progestogen, oestrogen, combined oral contraceptive, progestin only contraceptive, gonadotrophin-releasing hormone, danazol and vitamin B6. RESULTS: The rate of recording of premenstrual syndrome diagnoses decreased over calendar time from 8.43 in 1995 to 1.72 in 2013. Of the 38,614 women without treatment in the 6 months prior to diagnosis, 54% received a potentially premenstrual syndrome related prescription on the day of their first PMS record while 77% received a prescription in the 24 months after. Between 1995 and 1999, the majority of women were prescribed progestogens (23%) or vitamin B6 (20%) on the day of their first PMS record; after 1999, these figures fell to 3% for progestogen and vitamin B6 with the majority of women instead being prescribed a selective serotonin reuptake inhibitor (28%) or combined oral contraceptive (17%). CONCLUSIONS: Recording of premenstrual syndrome diagnoses in UK primary care has declined substantially over time and preferred prescription treatment has changed from progestogen to selective serotonin reuptake inhibitor and combined oral contraceptives. PMID- 26993624 TI - Validity of breast, lung and colorectal cancer diagnoses in administrative databases: a systematic review protocol. AB - INTRODUCTION: Breast, lung and colorectal cancers constitute the most common cancers worldwide and their epidemiology, related health outcomes and quality indicators can be studied using administrative healthcare databases. To constitute a reliable source for research, administrative healthcare databases need to be validated. The aim of this protocol is to perform the first systematic review of studies reporting the validation of International Classification of Diseases 9th and 10th revision codes to identify breast, lung and colorectal cancer diagnoses in administrative healthcare databases. METHODS AND ANALYSIS: This review protocol has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 statement. We will search the following databases: MEDLINE, EMBASE, Web of Science and the Cochrane Library, using appropriate search strategies. We will include validation studies that used administrative data to identify breast, lung and colorectal cancer diagnoses or studies that evaluated the validity of breast, lung and colorectal cancer codes in administrative data. The following inclusion criteria will be used: (1) the presence of a reference standard case definition for the disease of interest; (2) the presence of at least one test measure (eg, sensitivity, positive predictive values, etc) and (3) the use of data source from an administrative database. Pairs of reviewers will independently abstract data using standardised forms and will assess quality using a checklist based on the Standards for Reporting of Diagnostic accuracy (STARD) criteria. ETHICS AND DISSEMINATION: Ethics approval is not required. We will submit results of this study to a peer-reviewed journal for publication. The results will serve as a guide to identify appropriate case definitions and algorithms of breast, lung and colorectal cancers for researchers involved in validating administrative healthcare databases as well as for outcome research on these conditions that used administrative healthcare databases. TRIAL REGISTRATION NUMBER: CRD42015026881. PMID- 26993625 TI - Sample size calculations in clinical research should also be based on ethical principles. AB - Sample size calculations based on too narrow a width, or with lower and upper confidence limits bounded by fixed cut-off points, not only increase power-based sample sizes to ethically unacceptable levels (thus making research practically unfeasible) but also greatly increase the costs and burdens of clinical trials. We propose an alternative method of combining the power of a statistical test and the probability of obtaining adequate precision (the power of the confidence interval) with an acceptable increase in power-based sample sizes. PMID- 26993626 TI - Major neutrophil functions subverted by Porphyromonas gingivalis. AB - Polymorphonuclear leukocytes (neutrophils) constitute an integrated component of the innate host defense in the gingival sulcus/periodontal pocket. However, the keystone periodontal pathogen Porphyromonas gingivalis has in the course of evolution developed a number of capacities to subvert this defense to its own advantage. The present review describes the major mechanisms that P. gingivalis uses to subvert neutrophil homeostasis, such as impaired recruitment and chemotaxis, resistance to granule-derived antimicrobial agents and to the oxidative burst, inhibition of phagocytic killing while promoting a nutritionally favorable inflammatory response, and delay of neutrophil apoptosis. Studies in animal models have shown that at least some of these mechanisms promote the dysbiotic transformation of the periodontal polymicrobial community, thereby leading to inflammation and bone loss. It is apparent that neutrophil-P. gingivalis interactions and subversion of innate immunity are key contributing factors to the pathogenesis of periodontal disease. PMID- 26993627 TI - PrEP as Peri-conception HIV Prevention for Women and Men. AB - Daily oral tenofovir (TDF)-based pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy and recommended for men and women with substantial risk of HIV acquisition. The peri-conception period, the stage prior to pregnancy when condom use is necessarily reduced, has elevated HIV risk that can be mitigated by PrEP use. Data from a randomized trial suggest that peri-conception PrEP use by HIV-seronegative women does not increase the risk of pregnancy loss, birth defects or congenital anomalies, preterm birth, or infant growth faltering. Women considering PrEP use throughout pregnancy must weigh the known increased risk of HIV acquisition with unknown risks of drug effects on infant growth. PrEP has been used safely by HIV-seronegative men with HIV-seropositive female partners who have become pregnant. As an effective user-controlled HIV prevention strategy, PrEP offers autonomy and empowerment for HIV prevention and can be recommended alongside antiretroviral therapy, fertility screening, vaginal self insemination, intercourse timed to peak fertility, medically assisted reproduction, and other safer conception strategies to provide multiple options. The integration of PrEP into safer conception programs is warranted and will safely reduce HIV transmission to women, men, and children during the peri conception period. PMID- 26993628 TI - A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma. AB - BACKGROUND: Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1 prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller. METHODS: Five hundred seventy eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide). RESULTS: Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment. CONCLUSIONS: Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01582503. PMID- 26993629 TI - Stop or go? Preventive cognitive therapy with guided tapering of antidepressants during pregnancy: study protocol of a pragmatic multicentre non-inferiority randomized controlled trial. AB - BACKGROUND: Approximately 6.2 % of women in the USA and 3.7 % of women in the UK, use Selective Serotonin Reuptake Inhibitors (SSRIs) during their pregnancies because of depression and/or anxiety. In the Netherlands, this prevalence is around 2 %. Nonetheless, SSRI use during pregnancy is still controversial. On the one hand SSRIs may be toxic to the intrauterine developing child, while on the other hand relapse or recurrence of depression during pregnancy poses risks for both mother and child. Among patients and professionals there is an urgent need for evidence from randomized studies to make rational decisions regarding continuation or tapering of SSRIs during pregnancy. At present, no such studies exist. METHODS/DESIGN: 'Stop or Go' is a pragmatic multicentre randomized non inferiority trial among 200 pregnant women with a gestational age of less than 16 weeks who use SSRIs without clinically relevant depressive symptoms. Women allocated to the intervention group will receive preventive cognitive therapy with gradual, guided discontinuation of SSRIs under medical management (STOP). Women in the control group will continue the use of SSRIs (GO). Primary outcome will be the (cumulative) incidence of relapse or recurrence of maternal depressive disorder (as assessed by the Structured Clinical Interview for DSM disorders) during pregnancy and up to three months postpartum. Secondary outcomes will be child outcome (neonatal outcomes and psychomotor and behavioural outcomes up to 24 months postpartum), and health-care costs. Total study duration for participants will be therefore be 30 months. We specified a non-inferiority margin of 15 % difference in relapse risk. DISCUSSION: This study is the first to investigate the effect of guided tapering of SSRIs with preventive cognitive therapy from early pregnancy onwards as compared to continuation of SSRIs during pregnancy. We will study the effects on both mother and child with a pragmatic approach. Additionally, the study examines cost effectiveness. If non-inferiority of preventive cognitive therapy with guided tapering of SSRIs compared to intended continuation of SSRIs is demonstrated for the primary outcome, this may be the preferential strategy during pregnancy. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR4694 ; registration date: 16-jul-2014. PMID- 26993630 TI - Neurokinin-3 Receptor Binding in Guinea Pig, Monkey, and Human Brain: In Vitro and in Vivo Imaging Using the Novel Radioligand, [18F]Lu AF10628. AB - BACKGROUND: Previous autoradiography studies have suggested a marked interspecies variation in the neuroanatomical localization and expression levels of the neurokinin 3 receptor, with high density in the brain of rat, gerbil, and guinea pig, but at the time offered no conclusive evidence for its presence in the human brain. Hitherto available radioligands have displayed low affinity for the human neurokinin 3 receptor relative to the rodent homologue and may thus not be optimal for cross-species analyses of the expression of this protein. METHODS: A novel neurokinin 3 receptor radioligand, [(18)F]Lu AF10628 ((S)-N-(cyclobutyl(3 fluorophenyl)methyl)-8-fluoro-2-((3-[(18)F]-fluoropropyl)amino)-3-methyl-1-oxo 1,2-dihydroisoquinoline-4-carboxamide), was synthesized and used for autoradiography studies in cryosections from guinea pig, monkey, and human brain as well as for positron emission tomography studies in guinea pig and monkey. RESULTS: The results confirmed previous observations of interspecies variation in the neurokinin 3 receptor brain localization with more extensive distribution in guinea pig than in primate brain. In the human brain, specific binding to the neurokinin 3 receptor was highest in the amygdala and in the hypothalamus and very low in other regions examined. Positron emission tomography imaging showed a pattern consistent with that observed using autoradiography. The radioactivity was, however, found to accumulate in skull bone, which limits the use of this radioligand for in vivo quantification of neurokinin 3 receptor binding. CONCLUSION: Species differences in the brain distribution of neurokinin 3 receptors should be considered when using animal models for predicting human neurokinin 3 receptor pharmacology. For positron emission tomography imaging of brain neurokinin 3 receptors, additional work is required to develop a radioligand with more favorable in vivo properties. PMID- 26993631 TI - Modulatory Effects of Mild Carbon Monoxide Exposure in the Developing Mouse Cochlea. AB - Carbon monoxide (CO) is well known as a highly toxic poison at high concentrations, yet in physiologic amounts it is an endogenous biological messenger in organs such as the internal ear and brain. In this study we tested the hypothesis that chronic very mild CO exposure at concentrations 25-ppm increases the expression of oxidative stress protecting enzymes within the cellular milieu of the developing inner ear (cochlea) of the normal CD-1 mouse. In addition we tested also the hypothesis that CO can decrease the pre-existing condition of oxidative stress in the mouse model for the human medical condition systemic lupus erythematosus by increasing two protective enzymes heme-oxygenase 1 (HO-1), and superoxide dismutase-2 (SOD-2). CD-1 and MRL/lpr mice were exposed to mild CO concentrations (25 ppm in air) from prenatal only and prenatal followed by early postnatal day 5 to postnatal day 20. The expression of cell markers specific for oxidative stress, and related neural/endothelial markers were investigated at the level of the gene products by immunohistochemistry, proteomics and mRNA expression (quantitative real time-PCR). We found that in the CD-1 and MRL/lpr mouse cochlea SOD-2 and HO-1 were upregulated. In this mouse model of autoimmune disease defense mechanism are attenuated, thus mild CO exposure is beneficial. Several genes (mRNA) and proteins detected by proteomics involved in cellular protection were upregulated in the CO exposed CD-1 mouse and the MRL/lpr mouse. PMID- 26993632 TI - Egg consumption and risk of type 2 diabetes: a prospective study and dose response meta-analysis. AB - AIMS/HYPOTHESIS: In this study, we aimed to investigate the association between egg consumption and type 2 diabetes risk in the Cohort of Swedish Men and to conduct a meta-analysis to summarise available prospective evidence on this association. METHODS: We followed 39,610 men (aged 45-79 years) from 1998 up to 2012 for incident type 2 diabetes. Egg consumption was assessed at baseline using a food frequency questionnaire. HRs (95% CIs) were estimated using Cox proportional hazards regression models. We searched PubMed (up to 14 December 2015) and reference lists of retrieved articles to identify eligible studies for meta-analysis. RESULTS: During the 15 years of follow up, 4,173 men were diagnosed with type 2 diabetes. Compared with men who consumed eggs <1 time/week, the multivariable-adjusted HRs were 0.98 (95% CI 0.92, 1.05), 1.11 (95% CI 0.99, 1.24) and 1.11 (95% CI 0.95, 1.29) for egg consumption 1-2, 3-4 and >=5 times/week, respectively (p trend = 0.06). In a random-effects dose-response meta analysis, heterogeneity in the overall estimate was partly explained by differences across regions. The overall HRs for type 2 diabetes for each 3 times/week increment in consumption were 1.18 (95% CI 1.13, 1.24) in five US studies (I (2) = 0%) and 0.97 (95% CI 0.90, 1.05) in seven non-US studies. CONCLUSIONS/INTERPRETATION: Our findings in Swedish men do not support an association between egg consumption and risk of type 2 diabetes. In a meta analysis, frequent egg consumption was associated with a higher risk of type 2 diabetes in US studies only. Egg consumption habits and associated overall dietary patterns may differ between populations and could potentially explain the discrepancies between reported results. Given the inconsistent results, this relationship warrants further study. PMID- 26993633 TI - Insights into metabolic disease from studying genetics in isolated populations: stories from Greece to Greenland. AB - Over the last 10 years substantial progress has been made in our understanding of the genetic basis for type 2 diabetes and related traits. These developments have been facilitated by technological advancements that have allowed comprehensive genome-wide assessments of the impact of common genetic variation on disease risk. Current efforts are now focused on extending this to genetic variants in the rare and low-frequency spectrum by capitalising on next-generation sequencing technologies. This review discusses the important contributions that studies in isolated populations are making to this effort for diabetes and metabolic disease, drawing on specific examples from populations in Greece and Greenland. This review summarises a presentation given at the 'Exciting news in genetics of diabetes' symposium at the 2015 annual meeting of the EASD, with topics presented by Eleftheria Zeggini and Torben Hansen, and an overview by the Session Chair, Anna Gloyn. PMID- 26993634 TI - O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis. AB - AIMS/HYPOTHESIS: O-GlcNAcylation is implicated in modulating mitochondrial function, which is closely involved in regulating muscle metabolism. The presence of O-GlcNAcase (OGA), the enzyme involved in the removal of O-GlcNAc, in mitochondria was recently confirmed in rats. In the present study, we investigated the regulation of myogenesis and muscle insulin sensitivity to OGA in mice, with a focus on mitochondria. METHODS: C57BL/6J mice fed a high-fat diet for 4 months were used to observe mitochondrial density, activity and O GlcNAcylation in muscle. Small interfering RNA and overexpression vectors were used to modulate protein content in vitro. RESULTS: High-fat feeding decreased the OGA level and largely increased mitochondrial O-GlcNAcylation in mouse skeletal muscle that was accompanied by decreased levels of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), decreased mitochondrial density and disrupted mitochondrial complex activities. Knockdown of OGA in C2C12 myoblasts promoted PGC-1alpha degradation, resulting in the suppression of mitochondrial biogenesis and myogenesis, whereas neither knockdown of O-GlcNAc transferase nor overexpression of OGA had significant effects on myogenesis. Mitochondrial dysfunction as evidenced by decreased ATP content and increased reactive oxygen species production, and increased lipid and protein oxidation was observed in both myoblasts and myotubes after OGA knockdown. Meanwhile, elevated O-GlcNAcylation through either OGA knockdown or treatment with the OGA inhibitor PUGNAc and the O-GlcNAc transferase substrate D-GlcNAc suppressed myotube insulin signalling transduction and glucose uptake. OGA overexpression had no significant effect on insulin sensitivity but sufficiently improved the insulin resistance induced by D-GlcNAc treatment. CONCLUSIONS/INTERPRETATION: These data suggest that OGA can modulate mitochondrial density via PGC-1alpha and mitochondrial function via protein O GlcNAcylation. In this manner, OGA appears to play a key role in myogenesis and the development of muscle insulin resistance. PMID- 26993635 TI - Neuromuscular junction immaturity and muscle atrophy are hallmarks of the ColQ deficient mouse, a model of congenital myasthenic syndrome with acetylcholinesterase deficiency. AB - The collagen ColQ anchors acetylcholinesterase (AChE) in the synaptic cleft of the neuromuscular junction (NMJ). It also binds MuSK and perlecan/dystroglycan, 2 signaling platforms of the postsynaptic domain. Mutations in ColQ cause a congenital myasthenic syndrome (CMS) with AChE deficiency. Because the absence of AChE does not fully explain the complexity of the syndrome and there is no curative treatment for the disease, we explored additional potential targets of ColQ by conducting a large genetic screening of ColQ-deficient mice, a model for CMS with AChE deficiency, and analyzed their NMJ and muscle phenotypes. We demonstrated that ColQ controls the development and the maturation of the postsynaptic domain by regulating synaptic gene expression. Notably, ColQ deficiency leads to an up-regulation of the 5 subunits of the nicotinic acetylcholine receptor (AChR), leading to mixed mature and immature AChRs at the NMJ of adult mice. ColQ also regulates the expression of extracellular matrix (ECM) components. However, whereas the ECM mRNAs were down-regulated in vitro, compensation seemed to occur in vivo to maintain normal levels of these mRNAs. Finally, ColQ deficiency leads to a general atrophic phenotype and hypoplasia that affect fast muscles. This study points to new specific hallmarks for this CMS.-Sigoillot, S. M., Bourgeois, F., Karmouch, J., Molgo, J., Dobbertin, A., Chevalier, C., Houlgatte, R., Leger, J., Legay, C. Neuromuscular junction immaturity and muscle atrophy are hallmarks of the ColQ-deficient mouse, a model of congenital myasthenic syndrome with acetylcholinesterase deficiency. PMID- 26993636 TI - Evaluation of a Decision-Making Curriculum for Teaching Adolescents with Disabilities to Resist Negative Peer Pressure. AB - This study was designed to assess the impact of a decision-making curriculum (PEER-DM) on the social peer relationship knowledge and self-protective decision making skills of adolescents with disabilities in hypothetical situations involving negative peer pressure. A randomized design was used to assign students with disabilities from self-contained special education classes to an intervention group (n = 22) or a wait-list control group (n = 20). ANCOVA analyses, using pretest scores as covariates, indicated that students who were trained on PEER-DM had significantly higher effective decision-making action and correct risk perception scores, relative to participants in the control group. This study provides supporting evidence that PEER-DM is a promising intervention for students with disabilities, including those with identified autism spectrum disorders, during transition years to help them develop a better understanding of positive and negative peer relationships and learn systematic decision-making skills for improved handling of social situations in the school and community, especially situations involving negative peer pressure. The study adds credence to using systematic, strategy-based decision making interventions designed to address the cognitive, emotional and motivational processes underlying adolescent decision making in sensitive interpersonal situations involving peer pressure. The study points to the lack of preparedness to handle situations of negative peer pressure as a serious social and health risk for adolescents with disabilities that deserves urgent and concerted attention in transition services programming. Implications for future curriculum-development efforts and replication of treatment findings are discussed. Future research examining disability-specific patterns of decision-making in peer situations and comparisons with typically developing populations is recommended. PMID- 26993637 TI - Under the Weather: Legionellosis and Meteorological Factors. AB - The incidence of legionellosis, caused by the bacteria Legionella which are commonly found in the environment, has been increasing in New Jersey (NJ) over the last decade. The majority of cases are sporadic with no known source of exposure. Meteorological factors may be associated with increases in legionellosis. Time series and case-crossover study designs were used to evaluate associations of legionellosis and meteorological factors (temperature (daily minimum, maximum, and mean), precipitation, dew point, relative humidity, sea level pressure, wind speed (daily maximum and mean), gust, and visibility). Time series analyses of multi-factor models indicated increases in monthly relative humidity and precipitation were positively associated with monthly legionellosis rate, while maximum temperature and visibility were inversely associated. Case crossover analyses of multi-factor models indicated increases in relative humidity occurring likely before incubation period was positively associated, while sea level pressure and visibility, also likely preceding incubation period, were inversely associated. It is possible that meteorological factors, such as wet, humid weather with low barometric pressure, allow proliferation of Legionella in natural environments, increasing the rate of legionellosis. PMID- 26993638 TI - Transanal NOTES total mesorectal excision (TME) in patients with rectal cancer: Is anatomy better preserved? AB - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) and single incision laparoscopy are spreading worldwide. Total mesorectal excision (TME), the standard treatment for patients with distal rectal tumors, is usually performed in an "up-to-down" approach, either laparoscopically (LAPTME) or as an open procedure. We have already reported a NOTES-inspired, transanal, "down-to up" variant of TME (NOTESTME). The main aim of this study was to assess the quality of the resected specimen in patients who had undergone either NOTESTME or LAPTME. METHODS: All patients with distal rectal neoplasia presenting between January 2011 and December 2014 were considered for the study. Additional inclusion criteria comprised American Society of Anesthesiologists score <= III and the absence of previous open surgery. Assignment to either group was sequential and based on the rank of inclusion in the study. The primary endpoint was the macroscopic quality of the specimen. Secondary endpoints included nerve visualization, tumor perforation, operating time, status of margins, and number of retrieved nodes. RESULTS: Eighteen patients (6 men, 12 women) were in the NOTESTME group and 15 (7 men, 8 women) in the LAPTME group, respectively. The TME specimen was considered complete or mainly regular in 16 patients who had undergone NOTESTME (88.9 %) and in 11 patients who had undergone LAPTME (73.3 %), (p > 0.05). During the procedure, we visually identified the neurovascular bundles of Walsh in 14 patients in the NOTESTME group (77.8 %) and in only 5 patients in the LAPTME group (33.3 %), (p < 0.05). Mean operative time was 245 min (range 155-440 min) in the NOTESTME group and 275 min (range 180-400 min) in the LAPTME group (p > 0.05). A median of 11 nodes per specimen (range 8-22 nodes) was retrieved in the NOTESTME group and 12 nodes (range 6-41 nodes) in the LAPTME group, respectively (p > 0.05). Distal and radial margins were comparable in both groups. CONCLUSIONS: Compared to the LAPTME, the NOTESTME seems to be associated with a more frequent intraoperative identification of the sacral nerves. However, the difference in overall quality of the retrieved specimen, although favoring NOTESTME, did not reach statistical significance in this small series. PMID- 26993639 TI - NMR assignments of the macro domain from Middle East respiratory syndrome coronavirus (MERS-CoV). AB - The newly emerging human pathogen, Middle East respiratory syndrome coronavirus (MERS-CoV), contains a macro domain in the highly conserved N-terminal region of non-structural protein 3. Intense research has shown that macro domains bind ADP ribose and other derivatives, but it still remains intangible about their exact function. In this study we report the preliminary structural analysis through solution NMR spectroscopy of the MERS-CoV macro domain. The near complete NMR assignments of MERS-CoV macro domain provide the basis for subsequent structural and biochemical investigation in the context of protein function. PMID- 26993640 TI - From tokenism to empowerment: progressing patient and public involvement in healthcare improvement. AB - BACKGROUND: There have been repeated calls to better involve patients and the public and to place them at the centre of healthcare. Serious clinical and service failings in the UK and internationally increase the urgency and importance of addressing this problem. Despite this supportive policy context, progress to achieve greater involvement is patchy and slow and often concentrated at the lowest levels of involvement. METHODS: A selective narrative literature search was guided by the authors' broad expertise, covering a range of disciplines across health and social care, policy and research. Published systematic literature reviews were used to identify relevant authors and publications. Google and hand searches of journal articles and reference lists and reports augmented identification of recent evidence. RESULTS: Patients and the wider public can be involved at most stages of healthcare, and this can have a number of benefits. Uncertainty persists about why and how to do involvement well and evaluate its impact, how to involve and support a diversity of individuals, and in ways that allow them to work in partnership to genuinely influence decision-making. This exposes patient and public involvement (PPI) to criticisms of exclusivity and tokenism. CONCLUSIONS: Current models of PPI are too narrow, and few organisations mention empowerment or address equality and diversity in their involvement strategies. These aspects of involvement should receive greater attention, as well as the adoption of models and frameworks that enable power and decision-making to be shared more equitably with patients and the public in designing, planning and co-producing healthcare. PMID- 26993641 TI - A cross-sectional observational study of high override rates of drug allergy alerts in inpatient and outpatient settings, and opportunities for improvement. AB - OBJECTIVES: To evaluate how often and why providers overrode drug allergy alerts in both the inpatient and outpatient settings. DESIGN: A cross-sectional observational study of drug allergy alerts generated over a 3-year period between 1 January 2009 and 31 December 2011. SETTING: A 793-bed tertiary care teaching affiliate of Harvard Medical School and 36 primary care practices. PARTICIPANTS: Drug allergy alerts were displayed for a total of 29 420 patients across both settings. MAIN OUTCOME MEASURES: Proportion of drug allergy alerts displayed and overridden, proportion of appropriate overrides, proportion of overrides in each medication class, different reasons for overriding and types of reactions overridden. RESULTS: A total of 158 023 drug allergy alerts were displayed, 131 615 (83%) in the inpatient setting and 26 408 (17%) in the outpatient setting; 128 157 (81%) of which were overridden. A random sample of inpatient (n=200, 0.19%) and outpatient (n=50, 0.25%) alert overrides were screened for appropriateness, with >96% considered appropriate. Alerts for some drug classes, such as 'non-antibiotic sulfonamides', were overridden for >81% of prescriptions in both settings. The most common override reason was patient has taken previously without allergic reaction. In the inpatient setting alone, 70.9% of alerts that warned against the risk of anaphylaxis were overridden. CONCLUSIONS: The information contained in patients' drug allergy lists needs to be regularly updated. Most of the drug allergy alerts were overridden, with the majority of alert overrides in the subsample considered appropriate. Some of the rules for these alerts should be carefully reviewed and modified, or removed. Further research is needed to understand providers' overriding of alerts that warned against the risk of 'anaphylaxis', which are more concerning with respect to patient safety. PMID- 26993645 TI - Errata. PMID- 26993646 TI - Capillary telangiectasia mimicking an active demyelinating lesion in a patient with multiple sclerosis. PMID- 26993642 TI - The Influence of Fatty Acid Methyl Esters (FAMEs) in the Biochemistry and the Na(+)/K(+)-ATPase Activity of Culex quinquefasciatus Larvae. AB - Culex quinquefasciatus is the main vector of lymphatic filariasis and combating this insect is of great importance to public health. There are reports of insects that are resistant to the products currently used to control this vector, and therefore, the search for new products has increased. In the present study, we have evaluated the effects of fatty acid methyl esters (FAMEs) that showed larvicidal activity against C. quinquefasciatus, on glucose, total protein, and triacylglycerol contents and Na(+)/K(+)-ATPase activity in mosquito larvae. The exposure of the fourth instar larvae to the compounds caused a decrease in the total protein content and an increase in the activity of the Na(+)/K(+)-ATPase. Furthermore, the direct effect of FAMEs on cell membrane was assessed on purified pig kidney Na(+)/K(+)-ATPase membranes, erythrocyte ghost membranes, and larvae membrane preparation. No modifications on total phospholipids and cholesterol content were found after FAMEs 20 min treatment on larvae membrane preparation, but only 360 ug/mL FAME 2 was able to decrease total phospholipid of erythrocyte ghost membrane. Moreover, only 60 and 360 ug/mL FAME 3 caused an activation of purified Na(+)/K(+)-ATPase, that was an opposite effect of FAMEs treatment in larvae membrane preparation, and caused an inhibition of the pump activity. These data together suggest that maybe FAMEs can modulate the Na(+)/K(+)-ATPase on intact larvae for such mechanisms and not for a direct effect, one time that the direct effect of FAMEs in membrane preparation decreased the activity of Na(+)/K(+)-ATPase. The biochemical changes caused by the compounds were significant and may negatively influence the development and survival of C. quinquefasciatus larvae. PMID- 26993643 TI - Changes in Individual and Social Environmental Characteristics in Relation to Changes in Physical Activity: a Longitudinal Study from Primary to Secondary School. AB - PURPOSE: Physical activity (PA) strongly decreases when children make the transition from primary to secondary school. The study aimed to investigate how individual and social environmental factors toward PA changed when children (11 12 years) made the transition from primary to secondary school (13-14 years) and how changes in these factors were related to changes in different PA domains. METHODS: In total, 321 children (48.9 % girls) and one of their parents both filled out a questionnaire concerning individual (i.e., attitude, self-efficacy, perceived benefits, and barriers of PA) and social environmental factors related to PA (parental support, friend's co-participation, parental trust in child's ability to be physically active, and social norm) in the last grade of primary school and 2 years later. Children wore an activity monitor for 7 days and self reported different domains of PA. RESULTS: Most individual and social factors became less positive toward PA after the transition to secondary school. Among girls, a more positive attitude and an increase in self-efficacy were related to an increase in average daily steps and sports during leisure, respectively. Among boys, a decrease in perceived barriers (lack of time and parental reported lack of transportation to sport activities) was related to a decrease in average daily steps. An increase in parental support and a decrease in the parental perceived barrier of not liking sports were related to an increase in sports during leisure. CONCLUSIONS: The prevention of adverse changes in individual and social factors toward physical activity may lead to a smaller decrease or an increase in physical activity. PMID- 26993647 TI - Safety in early experience with a direct anterior approach using fluoroscopic guidance with manual leg control for primary total hip arthroplasty: a consecutive one hundred and twenty case series. AB - BACKGROUND AND PURPOSE: An encouraging result with direct anterior approach (DAA) is attractive for both patients and surgeons. However, the risks associated with beginning to use DAA require further analysis of the learning curve and better countermeasures to ensure safety. We ask whether the complication rate in the DAA by the inexperienced surgeon could be decreased with specific countermeasures. Our hypothesis was that the complication rate would be low even in early phase of the learning curve using the DAA with these particular countermeasures. PATIENTS AND METHODS: We investigated a consecutive series of 120 primary THA using the DAA with four specific countermeasures; 1) defined exclusion criteria for DAA; 2) no positioning table; 3) use of fluoroscopy as much as required; and 4) having an experienced assistant for DAA (one who has performed the procedure in more than 100 cases). The operative time, the time of fluoroscopic use during the operation, intra and post-operative complications, re-operation for any reason, and cup and stem alignment were investigated. RESULTS: Although the operation times were similar, the duration of fluoroscopy decreased with surgeons' experience. There were no intra-operative complications and no re-operations for any reason. One anterior dislocation was observed in one patient. The mean cup inclination and anteversion angle was 39.7 degrees +/- 7.6 degrees and 30.3 degrees +/- 7.6 degrees ; 43.3 % of stems were positioned in flexion, 55.8 % in the neutral position on the lateral view. CONCLUSION: We demonstrated a lower complication rate during our early experience with the DAA using four countermeasures. Using these countermeasures for the first 40 cases may be useful for surgeons who are considering DAA. PMID- 26993648 TI - Detecting Aspiration and Penetration Using FEES With and Without Food Dye. AB - The objective of this investigation was to determine if there were differences in identifying airway invasion (penetration or aspiration) during fiberoptic endoscopic evaluations of swallowing (FEES) for green-dyed versus non-dyed liquids. Forty adult inpatients in an acute care hospital underwent FEES, with both green-dyed liquids and naturally white liquids. Three speech-language pathologists rated aspiration and penetration for trials of nectar-thick milk and thin milk, both with and without green food dye. A subset of participants having excess pharyngeal/laryngeal secretions, as measured by the Secretions Severity Scale, were also analyzed for a difference in the detection of airway invasion and pharyngeal residue. No significant differences were found between dyes in airway invasion across all bolus types within participants. Significant differences were found in penetration ratings for large volumes of thin liquids (90 ml), between participants. When examining only discrepant airway invasion judgments for green-white swallow pairs, statistically significantly deeper airway invasion was measured for green-dyed boluses versus white for three of the five bolus types. Repeat rater reliability was better for dyed versus undyed liquids. Findings suggest that the use of green dye may allow for improved judgment of airway invasion. PMID- 26993649 TI - CT colonography for surveillance of patients with colorectal cancer: Systematic review and meta-analysis of diagnostic efficacy. AB - PURPOSE: To review primary research evidence investigating performance of CT colonography for colorectal cancer surveillance. The financial impact of using CT colonography for surveillance was also estimated. METHODS: We identified primary studies of CT colonography for surveillance of colorectal cancer patients. A summary ROC curve was constructed. Inter-study heterogeneity was explored using the I2 value. Financial impact was estimated for a theoretical cohort of patients, based on Cancer Research UK statistics. RESULTS: Seven studies provided data on 880 patients. Five of seven studies (765 patients) were included for qualitative analysis. Sensitivity of CT colonography for detection of anastomotic recurrence was 95 % (95 % CI 62 - 100), specificity 100 % (95 % CI 75 - 100) and sensitivity for metachronous cancers was 100 %. No statistical heterogeneity was detected (I2 = 0 %). We estimated that CT colonography as a 'single test' alternative to colonoscopy and standard CT for surveillance would potentially save ?20,785,232 (L14,803,404) for an annual cohort of UK patients. CONCLUSION: CT colonography compares favourably to colonoscopy for detection of anastomotic recurrence and metachronous colorectal cancer, and appears financially beneficial. These findings should be considered alongside limitations of small patient numbers and high clinical heterogeneity between studies. KEY POINTS: * CT colonography compares favourably to colonoscopy/standard CT for colorectal cancer surveillance. * CT colonography offers single-test luminal, serosal and extra colonic assessment. * CT colonography is a potentially cost-saving alternative to standard surveillance protocols. PMID- 26993650 TI - Non-enhanced magnetic resonance imaging of unruptured intracranial aneurysms at 7 Tesla: Comparison with digital subtraction angiography. AB - PURPOSE: To prospectively evaluate non-contrast-enhanced 7-Tesla (T) MRA for delineation of unruptured intracranial aneurysms (UIAs) in comparison with DSA. MATERIAL AND METHODS: Forty patients with single or multiple UIAs were enrolled in this IRB-approved trial. Sequences acquired at 7 T were TOF MRA and non contrast-enhanced MPRAGE. All patients additionally underwent 3D rotational DSA. Two neuroradiologists individually analysed the following aneurysm and image features on a five-point scale in 2D and 3D image reconstructions: delineation of parent vessel, dome and neck; overall image quality; presence of artefacts. Interobserver accordance was assessed by the kappa coefficient. RESULTS: A total of 64 UIAs were detected in DSA and in all 2D and 3D MRA image reconstructions. Ratings showed comparable results for DSA and 7-T MRA when considering all image reconstructions. Highest ratings for individual image reconstructions were given for 2D MPRAGE and 3D TOF MRA. Interobserver accordance was almost perfect for the majority of ratings. CONCLUSION: This study demonstrates excellent delineation of UIAs using 7-T MRA within a clinical setting comparable to the gold standard, DSA. The combination of 7-T non-enhanced MPRAGE and TOF MRA for assessment of untreated UIAs is a promising clinical application of ultra-high-field MRA. KEY POINTS: * Non-enhanced 7-T MRA allowed excellent delineation of unruptured intracranial aneurysms (UIAs). * Image quality at 7-T was comparable with DSA considering both sequences. * Assessment of UIAs is a promising clinical application of ultra-high-field MRA. PMID- 26993651 TI - Quantitative assessment of morphology, T1rho, and T2 of shoulder cartilage using MRI. AB - OBJECTIVES: The aim of this study was to assess the feasibility of quantifying shoulder cartilage morphology and relaxometry in a clinically feasible scan time comparing different pulse sequences and assessing their reproducibility at 3 Tesla. METHODS: Three pulse sequences were compared for morphological assessments of shoulder cartilage thickness and volume (SPGR, MERGE, FIESTA), while a combined T1rho-T2 sequence was optimized for relaxometry measurements. The shoulders of six healthy subjects were scanned twice with repositioning, and the cartilage was segmented and quantified. The degree of agreement between the three morphological sequences was assessed using Bland-Altman plots, while the morphological and relaxometry reproducibility were assessed with root-mean-square coefficients of variation (RMS-CVs) RESULTS: Bland-Altman plots indicated good levels of agreement between the morphological assessments of the three sequences. The reproducibility of morphological assessments yielded RMS-CVs between 4.0 and 17.7 %. All sequences correlated highly (R > 0.9) for morphologic assessments with no statistically significant differences. For relaxometry assessments of humeral cartilage, RMS-CVs of 6.4 and 10.6 % were found for T1rho and T2, respectively. CONCLUSIONS: The assessment of both cartilage morphology and relaxometry is feasible in the shoulder with SPGR, humeral head, and T1rho being the more reproducible morphological sequence, anatomic region, and quantitative sequence, respectively. KEY POINTS: * The thin cartilage morphology can be assessed in the shoulder in vivo. * Non-invasive biochemical assessment of shoulder cartilage is feasible in vivo using MRI. PMID- 26993654 TI - Isolation, identification and genomic characterization of the Asian lineage Zika virus imported to China. PMID- 26993652 TI - Cognitive Function and Quality of Life in Community-Dwelling Seniors with Mild Cognitive Impairment in Taiwan. AB - The aims of this study were to examine the relationships between overall cognitive function and the quality of life (QOL) domains, and to compare the differences in these by age, gender, and educational level in community-dwelling seniors in Taiwan. A cross-sectional study was conducted, with the participants screened and recruited from Southern Tainan. The Saint Louis University Mental Status Examination was used to screen the cognitive status of the participants. A total of 144 seniors participated in this study were assessed using the Taiwanese version of WHOQOL-BREF. The results showed that the participants performed better in the cognitive domains of "figure identification" and "orientation" while they performed poor in "delayed recall" and "immediate paragraph recall". No significant relationship between cognitive function and overall QOL, but a positive relationship between cognitive function and the physical health domain of QOL was found. The findings of this study provide valuable information for community healthcare providers. PMID- 26993655 TI - Expansion sphincter pharyngoplasty for obstructive sleep apnea: an update to the recent meta-analysis. PMID- 26993656 TI - Clinical impact of malnutrition on complication rate and length of stay in elective ENT patients: a prospective cohort study. AB - Malnutrition is considered as an independent risk factor for morbidity, mortality and a prolonged hospital stay for in-hospital patients. While most available data on the impact of malnutrition on health-related and financial implications refer to gastroenterologic or abdominal surgery patients, little is known about the impact of malnutrition on Ear Nose Throat (ENT)/head and neck surgery patients. The objective of this study was to investigate the impact of malnutrition on morbidity and length of hospital stay in an elective ENT/head and neck surgery patient cohort. The study was performed as a single-center, prospective cohort study at a tertiary referral centre. Nutritional risk at admission was assessed using the NRS-2002 screening tool. Multivariate regression models were used to determine independent risk factors for complications and a prolonged hospitalization. Three hundred fifty one participants were included in the study. A malignant disease was found in 62 participants (17.7 %). 62 patients (17.7 %) were at a moderate to severe risk of malnutrition. A bad general health condition and complications during hospital stay could be identified as independent risk factors for a prolonged hospitalization. Patients with a malignant tumor showed a more than fourfold higher risk of developing at least one complication. Malnutrition, however, was not statistically associated with a higher complication rate or a prolonged hospital stay. Our data suggests that malnutrition does not seem to play such an important role as a risk factor for complications and a prolonged hospital stay in ENT patients as it does in other disciplines like abdominal surgery or gastroenterology. PMID- 26993657 TI - Optimisation of the round window opening in cochlear implant surgery in wet and dry conditions: impact on intracochlear pressure changes. AB - To preserve residual hearing in cochlear implant candidates, the atraumatic insertion of the cochlea electrode has become a focus of cochlea implant research. In a previous study, intracochlear pressure changes during the opening of the round window membrane were investigated. In the current study, intracochlear pressure changes during opening of the round window membrane under dry and transfluid conditions were investigated. Round window openings were performed in an artificial cochlear model. Intracochlear pressure changes were measured using a micro-optical pressure sensor, which was placed in the apex. Openings of the round window membrane were performed under dry and wet conditions using a cannula and a diode laser. Statistically significant differences in the intracochlear pressure changes were seen between the different methods used for opening of the round window membrane. Lower pressure changes were seen by opening the round window membrane with the diode laser than with the cannula. A significant difference was seen between the dry and wet conditions. The atraumatic approach to the cochlea is assumed to be essential for the preservation of residual hearing. Opening of the round window under wet conditions produce a significant advantage on intracochlear pressure changes in comparison to dry conditions by limiting negative outward pressure. PMID- 26993658 TI - Comparison of red autofluorescing plaque and disclosed plaque-a cross-sectional study. AB - OBJECTIVES: The aim of this cross-sectional study was to assess the correlation between dental plaque scores determined by the measurement of red autofluorescence or by visualization with a two-tone solution. Clinical photographs were used for this study. MATERIALS AND METHODS: Overnight plaque from the anterior teeth of 48 participants was assessed for red fluorescence on photographs (taken with a QLF-camera) using a modified Quigley & Hein (mQH) index. A two-tone disclosing solution was applied. Total disclosed plaque was clinically assessed using the mQH index. In addition, total and blue disclosed plaque was scored on clinical photographs using the mQH index. RESULTS: A strong correlation was observed between the total disclosed plaque scored on photographs and the clinical scores (r = 0.70 at site level; r = 0.88 at subject level). The correlation between red fluorescent plaque and total plaque, as assessed on the photographs, was moderate to strong and significant (r = 0.50 at the site level; r = 0.70 at the subject level), with the total plaque scores consistently higher than the red fluorescent plaque scores. The correlation between red fluorescent plaque and blue disclosed plaque was weak to moderate and significant (r = 0.30 at the site level; r = 0.50 at the subject level). CONCLUSIONS: Plaque, as scored on white-light photographs, corresponds well with clinically assessed plaque. A weak to moderate correlation between red fluorescing plaque and total disclosed plaque or blue disclosed plaque was found. CLINICAL RELEVANCE: What at present is considered to be matured dental plaque, which appears blue following the application of a two-tone disclosing solution, is not in agreement with red fluorescent dental plaque assessment. PMID- 26993661 TI - Circadian clock of Drosophila montana is adapted to high variation in summer day lengths and temperatures prevailing at high latitudes. AB - Photoperiodic regulation of the circadian rhythms in insect locomotor activity has been studied in several species, but seasonal entrainment of these rhythms is still poorly understood. We have traced the entrainment of activity rhythm of northern Drosophila montana flies in a climate chamber mimicking the photoperiods and day and night temperatures that the flies encounter in northern Finland during the summer. The experiment was started by transferring freshly emerged females into the chamber in early and late summer conditions to obtain both non diapausing and diapausing females for the studies. The locomotor activity of the females and daily changes in the expression levels of two core circadian clock genes, timeless and period, in their heads were measured at different times of summer. The study revealed several features in fly rhythmicity that are likely to help the flies to cope with high variation in the day length and temperature typical to northern summers. First, both the non-diapausing and the diapausing females showed evening activity, which decreased towards the short day length as observed in the autumn in nature. Second, timeless and period genes showed concordant daily oscillations and seasonal shifts in their expression level in both types of females. Contrary to Drosophila melanogaster, oscillation profiles of these genes were similar to each other in all conditions, including the extremely long days in early summer and the cool temperatures in late summer, and their peak expression levels were not locked to lights-off transition in any photoperiod. Third, the diapausing females were less active than the non diapausing ones, in spite of their younger age. Overall, the study showed that D. montana clock functions well under long day conditions, and that both the photoperiod and the daily temperature cycles are important zeitgebers for seasonal changes in the circadian rhythm of this species. PMID- 26993659 TI - Significance of endothelial progenitor cells (EPC) for tumorigenesis of head and neck squamous cell carcinoma (HNSCC): possible marker of tumor progression and neovascularization? AB - OBJECTIVES: Angiogenesis and neovascularisation plays a crucial role for tumorigenesis and tumor progression in head and neck squamous cell carcinoma (HNSCC). The aim of our study was to investigate the neovascularization capacity by endothelial progenitor cells (EPC) in tumor patient as a possible predictor for tumor progression and tumor stage. MATERIALS AND METHODS: Therefore, we investigated the cell number and biologic activity by cell migration and colony forming ability of EPC. Cells were isolated from the peripheral venous blood of 79 patients who suffer HNSCC in different stages of disease. Thirty-three healthy individuals served as the control group. RESULTS: Significantly increased biological activities were reflected by expression of the migration rate (1027 +/ 1510) in comparison to the control group (632 +/- 269) and the clonal potency measured by colony-forming unit (CFU) (tumor patients (19.7 +/- 12.3) vs. control group (10.84 +/- 4.8)). To determine whether or not EPC number can be used as a valid prognostic marker for clinical outcome of tumor patients, we furthermore compared a "high EPC-number-subgroup" (HI) with a "low EPC-number-subgroup" (LO) in a Kaplan-Meier survival curve. The HI-subgroup shows herein clearly a worse outcome. CONCLUSIONS: Our findings indicate a possible pathway for EPC to play a critical role in the vasculogenesis and consequently in the progression of HNSCC. CLINICAL RELEVANCE: Our findings could serve as possible predictors for the neovascularisation potential in HNSCC tumor patients. PMID- 26993662 TI - Caspase-3 serves as an intracellular immune receptor specific for lipopolysaccharide in oyster Crassostrea gigas. AB - Apoptosis is a form of programmed cell death process controlled by a family of cysteine proteases called caspases, which plays a crucial role in the immune system homeostasis. The apoptosis and the detailed regulation mechanism have been well studied in vertebrate, but the information in lower animals, especially invertebrates, is still very limited. In the present study, Caspase-3 in the Pacific oyster Crassostrea gigas (designated CgCaspase-3) was enriched by lipopolysaccharide (LPS) affinity chromatography and further identified by MALDI TOF/TOF-mass spectrometry. The binding activity of CgCaspase-3 to LPS was confirmed by enzyme-linked immunosorbent assay, and surface plasmon resonance analysis revealed its high binding specificity and moderate binding affinity (KD = 1.08 * 10(-6) M) to LPS. The recombinant CgCaspase-3 exhibited high proteolytic activity to substrate Ac-DEVD-pNA and relatively weak activity to substrate Ac DMQD-pNA and Ac-VDQQD-pNA. The binding of CgCaspase-3 to LPS significantly inhibited its proteolytic activity toward AC-DEVD-pNA in vitro. The over expression of CgCaspase-3 leaded to the phosphatidylserine exposure on the external plasma membrane and the cleavage of poly (ADP-ribose) polymerase, which reduced cell viability, and finally induced cell apoptosis. But the cell apoptosis mediated by CgCaspase-3 in vivo was significantly inhibited by the treatment of LPS. These results collectively indicated that CgCaspase-3 could serve as an intracellular LPS receptor, and the interaction of LPS with CgCaspase 3 specifically inhibited the cell apoptosis induced by CgCaspase-3. PMID- 26993663 TI - Function of gC1qR in innate immunity of Chinese mitten crab, Eriocheir sinensis. AB - gC1qR is identified as the globular "head" binding protein of the C1q protein and performs an important function in innate immunity. A EsgC1qR gene was identified from the hepatopancreas of Eriocheir sinensis. EsgC1qR encodes a protein with 275 amino acids. Phylogenetic analysis showed that, together with crustaceans gC1qRs, EsgC1qR belongs to one group. EsgC1qR mRNA was detected in hemocytes, intestine, hepatopancreas, gills, eyestalk, heart, muscle, and nerve. The expression of the EsgC1qR transcript in the hepatopancreas could be regulated by lipopolysaccharides (LPS), peptidoglycans (PGN), Staphyloccocus aureus, or Vibrio parahaemolyticus. Recombinant EsgC1qR (rEsgC1qR) protein could bind to various bacteria, LPS, and PGN. rEsgC1qR protein also presents direct bacteria inhibitory activity. rEsgC1qR could interact with EsCnx or EsCrt. Therefore, from the results, we could speculate that EsgC1qR is involved in the innate immunity of Chinese mitten crab, E. sinensis. PMID- 26993660 TI - Caries-preventive effect of anti-erosive and nano-hydroxyapatite-containing toothpastes in vitro. AB - OBJECTIVES: The aim of the study was to investigate the caries-preventive effect of newly developed fluoride and fluoride-free toothpastes specially designed for erosion prevention. The hypothesis was that these products might also show superior caries-inhibiting effect than regular fluoride toothpastes, since they were designed for stronger erosive acid challenges. MATERIALS AND METHODS: Enamel specimens were obtained from bovine teeth and pre-demineralized (pH = 4.95/21 days) to create artificial caries lesions. Baseline mineral loss (DeltaZB) and lesion depth (LDB) were determined using transversal microradiography (TMR). Ninety specimens with a median DeltaZB (SD) of 6027 +/- 1546 vol% * MUm were selected and randomly allocated to five groups (n = 18). Treatments during pH cycling (14 days, 4 * 60 min demineralization/day) were brushing 2*/day with AmF (1400 ppm F-, anti-caries [AC]); AmF/NaF/SnCl2/Chitosan (700 ppm F-/700 ppm F /3500 ppm Sn2+, anti-erosion [AE1]); NaF/KNO3 (1400 ppm F-, anti-erosion [AE2]); nano-hydroxyapatite-containing (0 ppm F-, [nHA]); and fluoride-free toothpastes (0 ppm F-, negative control [NC]). Toothpaste slurries were prepared with mineral salt solution (1:3 wt/wt). After pH-cycling specimens presenting lesion, surface loss (mainly by NC and nHA) were discarded. For the remaining 77 specimens, new TMR analyses (DeltaZE/LDE) were performed. Changes in mineral loss (DeltaDeltaZ = DeltaZB - DeltaZE) and lesion depth (DeltaLD = LDB - LDE) were calculated. RESULTS: All toothpastes caused significantly less demineralization (lower DeltaDeltaZ) than NC (p < 0.05, ANOVA) except for nHA. The fluoride toothpastes did not differ significantly regarding DeltaDeltaZ and DeltaLD (p > 0.05, ANOVA). CONCLUSION/CLINICAL RELEVANCE: While both anti-erosive and anti-caries toothpastes reduced mineral loss to a similar extent, the fluoride-free nano hydroxyapatite-containing toothpaste seemed not to be suitable for inhibition of caries demineralization in vitro. PMID- 26993664 TI - Bone Mineral Density in Sheehan's Syndrome; Prevalence of Low Bone Mass and Associated Factors. AB - Hypopituitarism is a known cause of bone mineral loss. This study aimed to evaluate the frequency of osteopenia and osteoporosis in patients with Sheehan's syndrome (SS) and to determine the risk factors. This is a retrospective study of 60 cases of SS that have had a bone mineral density (BMD) measurement. Clinical, biological, and therapeutic data were collected. The parameters of osteodensitometry at the femoral neck and the lumbar spine of 60 patients with SS were compared with those of 60 age-, height-, and weight-matched control women. The mean age at BMD measurement was 49.4 +/- 9.9 yr (range: 25-76 yr). The mean duration of SS was 19.3 +/- 8.5 yr (range: 3-41 yr). All patients had corticotropin deficiency and were treated with hydrocortisone at a mean daily dose of 26.3 +/- 4.1 mg. Fifty-seven patients (95%) had thyrotropin deficiency and were treated with thyroxine at a mean daily dose of 124.3 +/- 47.4 ug. Thirty five of the 49 patients, aged less than 50 yr at diagnosis and having gonadotropin deficiency (71.4%), had estrogen-progesterone substitution. Osteopenia was present in 25 patients (41.7%) and osteoporosis in 21 (35.0%). The BMD was significantly lower in the group with SS than in the control group (p < 0.001). The odds ratio of osteopenia-osteoporosis was 3.1 (95% confidence interval: 1.4-6.8) at the femoral neck and 3.7 (95% confidence interval: 1.7-7.8) at the lumbar spine. The lumbar spine was more frequently affected by low bone mineral mass (p < 0.05). The duration of the disease and the daily dose of hydrocortisone were independently and inversely associated with BMD at the femoral neck. The daily dose of thyroxine was independently and inversely associated with BMD at the lumbar spine. Estrogen-progesterone replacement therapy was not associated with BMD. Low bone mineral mass was very common in patients with SS. The lumbar spine was more frequently affected. The duration of the disease and the doses of hydrocortisone and thyroxine were involved in bone mineral loss. PMID- 26993665 TI - Association between serum uric acid related genetic loci and diabetic kidney disease in the Chinese type 2 diabetes patients. AB - AIM: We aimed to investigate the association between uric acid related genetic loci and DKD susceptibility in type 2 diabetes patients. METHODS: Seventeen single nucleotide polymorphisms (SNPs) from thirteen loci related to serum uric acid were genotyped in 2,892 type 2 diabetes patients. Associations between SNPs and uric acid, SNPs and quantitative traits related to DKD or its susceptibility were evaluated. RESULTS: In this study, uric acid showed a strong association with DKD (OR=1.006, p<0.0001). GCKR rs780094, SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142, SLC22A12 rs505802 and NRXN2 rs506338 were positively associated with serum uric acid (p=3.79E-05, 0.0002, 2.04E-10, 2.23E-09, 0.0018 and 0.0015, respectively). SLC2A9 rs11722228 and SF1 rs606458 were significantly associated with DKD (OR=0.864, p=0.0440; OR=1.223, p=0.0038). SLC2A9 rs3775948 and ABCG2 rs2231142 were associated with DKD marginally (OR=0.878, p=0.0506; OR=0.879, p=0.0698). SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 and SF1 rs606458 were significantly associated with the estimated glomerular filtration rate (p=0.0005, 0.0006, 0.0003, and 0.0424, respectively). CONCLUSIONS: Our study indicated that the uric acid related alleles of SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 might affect DKD susceptibility and possibly through non-uric acid pathway in the Chinese people with type 2 diabetes. PMID- 26993666 TI - The Multidimensional Nutritional Niche. AB - The dietary generalist-specialist distinction plays a pivotal role in theoretical and applied ecology, conservation, invasion biology, and evolution and yet the concept remains poorly characterised. Diets, which are commonly used to define niche breadth, are almost exclusively considered in terms of foods, with little regard for the mixtures of nutrients and other compounds they contain. We use nutritional geometry (NG) to integrate nutrition with food-level approaches to the dietary niche and illustrate the application of our framework in the important context of invasion biology. We use an example that involves a model with four hypothetical nonexclusive scenarios. We additionally show how this approach can provide fresh theoretical insight into the ways nutrition and food choices impact trait evolution and trophic interactions. PMID- 26993667 TI - An Underground Revolution: Biodiversity and Soil Ecological Engineering for Agricultural Sustainability. AB - Soil organisms are an integral component of ecosystems, but their activities receive little recognition in agricultural management strategies. Here we synthesize the potential of soil organisms to enhance ecosystem service delivery and demonstrate that soil biodiversity promotes multiple ecosystem functions simultaneously (i.e., ecosystem multifunctionality). We apply the concept of ecological intensification to soils and we develop strategies for targeted exploitation of soil biological traits. We compile promising approaches to enhance agricultural sustainability through the promotion of soil biodiversity and targeted management of soil community composition. We present soil ecological engineering as a concept to generate human land-use systems, which can serve immediate human needs while minimizing environmental impacts. PMID- 26993668 TI - Injection of Mesenchymal Stem Cells as a Supplementary Strategy of Marrow Stimulation Improves Cartilage Regeneration After Lateral Sliding Calcaneal Osteotomy for Varus Ankle Osteoarthritis: Clinical and Second-Look Arthroscopic Results. AB - PURPOSE: To compare the clinical and second-look arthroscopic outcomes in patients undergoing arthroscopic marrow stimulation combined with lateral sliding calcaneal osteotomy for varus ankle osteoarthritis, with or without adipose derived mesenchymal stem cell (MSC) injection. METHODS: In this retrospective comparative study, 49 patients with varus ankle osteoarthritis underwent second look arthroscopy after arthroscopic marrow stimulation combined with lateral sliding calcaneal osteotomy between January 2010 and November 2012; 23 ankles underwent marrow stimulation alone (group 1), and 26 underwent marrow stimulation with MSC injection (group 2). The decision whether to receive the MSC injection, which was free of charge, was solely up to the patients. Second-look arthroscopies were performed at a mean of 12.5 months and 12.4 months postoperatively in group 1 and group 2, respectively. Clinical outcome measures included a visual analog scale (VAS) score for pain and the American Orthopaedic Foot & Ankle Society (AOFAS) score. The radiologic outcome variable was the talar tilt angle. On second-look arthroscopy, cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) grade. RESULTS: The mean VAS score improved significantly from 7.3 +/- 0.9 to 3.9 +/- 1.2 in group 1 and from 7.4 +/- 0.8 to 3.1 +/- 1.5 in group 2 at final follow-up (P < .001 for both groups). The mean AOFAS score also improved significantly from 64.4 +/- 4.1 to 79.6 +/- 7.7 in group 1 and from 63.5 +/- 4.2 to 84.2 +/- 7.9 in group 2 at final follow-up (P < .001 for both groups). The VAS and AOFAS scores were significantly better in group 2 than in group 1 (P = .040 and P = .047, respectively). ICRS grades were significantly correlated with clinical outcomes in both groups (all P < .05), and there were significant differences in ICRS grades between the groups (P < .05). The mean talar tilt angle improved significantly after lateral sliding calcaneal osteotomy in both groups and was significantly correlated with clinical outcomes and ICRS grade (all P < .05). CONCLUSIONS: In patients with varus ankle osteoarthritis who underwent lateral sliding calcaneal osteotomy, significant improvements in VAS and AOFAS scores, as well as better ICRS grades, were achieved at short-term follow-up after marrow stimulation with additional MSC injection compared with after marrow stimulation alone. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26993669 TI - Intraoperative Evaluation of Acetabular Morphology in Hip Arthroscopy Comparing Standard Radiography Versus Fluoroscopy: A Cadaver Study. AB - PURPOSE: To compare quantitative measurements of acetabular morphology obtained using intraoperative fluoroscopy, to standardized anteroposterior (AP) pelvis radiographs. METHODS: Ten dried human pelvis specimens (20 hips) were imaged using hip-centered fluoroscopy and standardized AP pelvis radiographs. Each hip was evaluated for acetabular version and coverage, including lateral center edge (LCE) angle, acetabular index (AI), total anterior and posterior coverage, and crossover sign. RESULTS: No statistically significant differences existed between the mean LCE angle (fluoroscopy 36.5 degrees +/- 8.3 degrees v plain films 36.1 degrees +/- 7.9 degrees , P = .59), acetabular index (0.6 degrees +/- 8.6 degrees v 0.2 degrees +/- 7.1 degrees , P = .61), ACM angle (44.0 degrees +/- 2.6 degrees v 44.1 degrees +/- 3.8 degrees , P = .89), Sharp's angle (31.8 degrees +/- 5.7 degrees v 32.4 degrees +/- 3.9 degrees , P = .44), and the total femoral coverage (80.9% +/- 6.4% v 80.7% +/- 7.5%, P = .83). Conversely, total anterior coverage (30.7% +/- 8.5% v 33.3% +/- 8.2%, P < .0001) appeared significantly decreased and the total posterior coverage (54.1% +/- 6.9% v 49.1% +/- 7.8%, P < .0001) appeared significantly increased in fluoroscopy compared with plain film radiographs. Fluoroscopy also failed to identify the presence of a crossover sign in 30% and underestimated the retroversion index (9% +/- 16%, v 13% +/- 16%, P = .016). CONCLUSIONS: The values for the LCE angle and AI determined by hip-centered fluoroscopy did not differ from those obtained by standardized AP plain film radiography. However, fluoroscopy leads to a more anteverted projection of the acetabulum with significantly decreased total anterior coverage, significantly increased total posterior coverage, and underestimated signs of retroversion compared with standardized AP pelvis radiography. CLINICAL RELEVANCE: This study shows reliable LCE and AI angles but significant differences in the projected anteversion of the acetabulum between standardized AP pelvis radiography and hip-centered fluoroscopy. PMID- 26993670 TI - Variability of Arthroscopy Case Volume in Orthopaedic Surgery Residency. AB - PURPOSE: To examine orthopaedic surgery case logs for arthroscopy case volume during residency training and to evaluate trends in case volume and variability over time. METHODS: Publicly available Accreditation Council for Graduate Medical Education surgical case logs from 2007 to 2013 for orthopaedic surgery residency were assessed for variability and case volume trends in shoulder, elbow, wrist, hip, knee, and ankle arthroscopy. The national average number of procedures performed in each arthroscopy category reported was directly compared from 2009 to 2013. The 10th and 90th percentile arthroscopy case volume was compared between 2007 and 2013 for shoulder and knee arthroscopy procedures. Subsequently, the difference between the 10th and 90th percentile arthroscopy case volume in each category in 2007 was compared with the difference between the 10th and 90th percentile arthroscopy case volume in each category in 2013. RESULTS: From 2007 to 2013, shoulder arthroscopy procedures performed per resident increased by 43.1% (P = .0001); elbow arthroscopy procedures increased by 28.0% (P = .00612); wrist arthroscopy procedures increased by 8.6% (P = .05); hip arthroscopy procedures, which were first reported in 2012, increased by 588.9%; knee arthroscopy procedures increased by 8.5% (P = .0435); ankle arthroscopy increased by 27.6% (P = .00149). The difference in knee and shoulder arthroscopy volume between residents in the 10th and 90th percentile in 2007 and residents in the 10th and 90th percentile in 2013 was not significant (P > .05). There was a 3.66 fold difference in knee arthroscopy volume between residents in the 10th and 90th percentile in 2007, whereas the difference was 3.36-fold in 2013 (P = .70). There was a 5.86-fold difference in shoulder arthroscopy case volume between residents in the 10th and 90th percentile in 2007, whereas the difference was 4.96-fold in 2013 (P = .29). CONCLUSIONS: The volume of arthroscopy cases performed by graduating orthopaedic surgery residents has significantly increased over time. There continues to be substantial variability in knee and shoulder arthroscopy case volume between residents in the 10th and 90th percentile. CLINICAL RELEVANCE: Variability in residency training is notable and may affect knowledge, skill, and practice patterns of surgeons. PMID- 26993671 TI - Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease. AB - Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of hydroxyurea in this subset of patients with SCD. Here, we report a case series of 14 pediatric patients with HbSC treated to maximum tolerated dose (MTD) with hydroxyurea. Those who failed to show clinical improvement after at least six months at MTD were offered phlebotomy in addition to hydroxyurea. Five out of 11 patients with HbSC who achieved MTD failed to demonstrate clinical improvement on hydroxyurea. Of the four placed on dual hydroxyurea and phlebotomy therapy, all showed at least partial clinical improvement. Percent dense red blood cells (%DRBC) were measured via an ADVIA hematology analyzer. A marked rise in percent dense cells preceded clinical complications in three patients. Dual therapy with hydroxyurea and phlebotomy may be an effective approach to patients with HbSC that do not experience improvement with hydroxyurea alone. Monitoring of %DRBC may predict adverse events and aid in assessing hydroxyurea compliance. Large scale clinical trials are needed to evaluate the safety and efficacy of hydroxyurea and hydroxyurea with phlebotomy in patients with HbSC disease. PMID- 26993673 TI - Journal of Vascular Surgery: Venous and Lymphatic Disorders Editors' message. PMID- 26993672 TI - Brief Communication: Discordant ability of the triglyceride to apolipoprotein B ratio to predict triglyceride-rich lipoprotein particle size in normal-weight and obese men. AB - The atherogenicity of triglyceride-rich lipoproteins (TRLs) is dependent of their particle size as it determines their metabolic fate. Since TRL possess a single apolipoprotein B (Apo B) molecule per particle, the triglyceride (TG)/Apo B ratio has been used as a convenient method to estimate TRL size. The aim of this study was to validate this approach by correlating the serum TG/Apo B ratio, and the TRL particle size measured by dynamic light scattering (DLS). Twenty-four male volunteers (12 normal-weight and 12 obese individuals) received a high-fat meal. Preprandial (0 h) and postprandial (2 and 4 h) serum samples were collected after meal ingestion, and TRLs were isolated. Serum TG and Apo B levels were quantified, and the TG/Apo B ratio was plotted against TRL particle size measured by DLS for correlation. A strong association between TRL particle size and serum TG/Apo B ratio for normal-weight subjects (P <= 0.001) was observed but not for obese subjects (P = 0.6116). TG/Apo B ratio correlates with particle size in healthy normal-weight males but not in obese individuals. Whether this ratio is useful to estimate TRL size in females and in other dyslipidemic patients should be subject of future investigations. PMID- 26993674 TI - The European multicenter cohort study on cyanoacrylate embolization of refluxing great saphenous veins. AB - OBJECTIVE: Cyanoacrylate (CA) embolization of refluxing great saphenous veins (GSVs) has been previously described. The outcomes from a multicenter study are still lacking. METHODS: A prospective multicenter study was conducted in seven centers in four European countries to abolish GSV reflux by endovenous CA embolization. Neither tumescent anesthesia nor postinterventional compression stockings were used. Varicose tributaries remained untreated until at least 3 months after the index treatment. Clinical examination, quality of life assessment, and duplex ultrasound evaluation were performed at 2 days and after 1, 3, 6, and 12 months. RESULTS: In 70 patients, of whom 68 (97.1%) were available for 12-month follow-up, 70 GSVs were treated. Two-day follow-up showed one proximal and one distal partial recanalization. Three additional proximal recanalizations were observed at 3-month (n = 2) and 6-month (n = 1) follow-up. Cumulative 12-month survival free from recanalization was 92.9% (95% confidence interval, 87.0%-99.1%). Mean (standard deviation) Venous Clinical Severity Score improved from 4.3 +/- 2.3 at baseline to 1.1 +/- 1.3 at 12 months. Aberdeen Varicose Vein Questionnaire score showed an improvement from 16.3 at baseline to 6.7 at 12 months (P < .0001). Side effects were generally mild; a phlebitic reaction occurred in eight cases (11.4%) with a median duration of 6.5 days (range, 2-12 days). Pain without a phlebitic reaction was observed in five patients (8.6%) for a median duration of 1 day (range, 0 -12 days). No serious adverse event occurred. Paresthesia was not observed. CONCLUSIONS: Endovenous CA embolization of refluxing GSVs is safe and effective without the use of tumescent anesthesia or compression stockings. PMID- 26993675 TI - Quantifying saphenous reflux. AB - BACKGROUND: Quantification of reflux is desirable in advanced chronic venous disease as clinical features are based on its adverse impact on ambulatory venous pressure (AMVP). Prior clinical observation suggests that reflux in a saphenous vein > 5 mm is likely significant. On the basis of normal calf pump mechanics, we hypothesized that a reflux volume >= 30 mL was necessary to upset pump equilibrium. METHODS: Venous laboratory data in 119 limbs with isolated saphenous reflux were analyzed. Reflux volume was calculated by duplex ultrasound (area * velocity * duration). The relationship of reflux volume to saphenous size, calf pump function (air plethysmography, AMVP), flow resistance (Poiseuille equation), and clinical severity were examined. RESULTS: Saphenous size had a bimodal relationship to reflux volume. Reflux volume of >= 30 mL occurred mostly (97% of limbs) with saphenous size of >= 5.5 mm, but 51% of saphenous veins >5.5 mm had reflux volumes <30 mL. This is because saphenous veins invariably carried less than their maximum reflux potential indicated by their size (Poiseuille equation). Variable additional focal resistance across refluxive valve cusps and narrower re-entry perforators is not taken into account when only saphenous truncal size is used for resistance calculation. Furthermore, the association of AMVP with reflux was found not to be based on a set (>= 30 mL) threshold but was variable, depending on existing calf pump mechanics, compensatory in some (12% of limbs) and aggravating reflux effects in others (26%). Calf pump abnormalities were found in 70% of refluxive limbs and in 44% (n = 16) of contralateral limbs without any reflux. Reflux volume was significantly higher overall in limbs with ulcer (C6), but the range overlapped with lesser clinical classes. Seven of 14 limbs with active ulcers had reflux volume >30 mL; six of seven limbs with active ulcers and reflux volume of <30 mL had calf pump abnormalities that would be poorly tolerant of reflux even at these smaller volumes. CONCLUSIONS: Saphenous size alone cannot be used as an indicator of significant reflux. More than two thirds of the limbs with isolated saphenous reflux have calf pump abnormalities, which also occurred without reflux in the opposite limb--a novel finding. This means that in addition to quantification of reflux volume, calf pump assessment such as with air plethysmography and AMVP is desirable in clinical classes 3 and higher for proper assessment. PMID- 26993676 TI - Progression of varicose veins and chronic venous insufficiency in the general population in the Edinburgh Vein Study. AB - OBJECTIVE: The natural history in the general population of chronic venous disease in the legs is not well understood. This has limited our ability to predict which patients will deteriorate and to assign clinical priorities. The aims of this study were to describe the progression of trunk varicose veins and chronic venous insufficiency (CVI) in the general population, to identify important lifestyle and clinical prognostic factors, and to determine the relationship between venous reflux and progression. METHODS: The Edinburgh Vein Study is a population-based cohort study in which randomly selected adults aged 18 to 64 years had an examination at baseline. This included a questionnaire on lifestyle and clinical factors, standardized assessment and classification of venous disease in the legs, and duplex scan to detect venous reflux in eight segments of each leg. A follow-up examination 13 years later included a reclassification of venous disease to ascertain progression in the development or increase in severity of varicose veins and CVI. RESULTS: Among 1566 adults seen at baseline, 880 had a follow-up examination, of whom 334 had trunk varicose veins or CVI at baseline and composed the study sample. The mean (standard deviation) duration of follow-up was 13.4 (0.4) years. Progression was found in 193 (57.8%), equivalent to 4.3% (95% confidence interval [CI], 3.7-4.9) annually. In 270 subjects with only varicose veins at baseline, 86 (31.9%) developed CVI, with the rate increasing consistently with age (P = .04). Almost all subjects (98%) with both varicose veins and CVI at baseline deteriorated. Progression of chronic venous disease did not differ by gender or leg, but a family history of varicose veins and history of deep venous thrombosis increased risk (odds ratio [OR], 1.85 [95% CI, 1.14-1.30] and 4.10 [95% CI, 1.07-15.71], respectively). Overweight was associated with increased risk of CVI in those with varicose veins (OR, 1.85; 95% CI, 1.10-3.12). Reflux in the superficial system increased the likelihood of progression, especially in combination with deep reflux (OR, 2.57; 95% CI, 1.55-4.25) and when located in the small saphenous vein (OR, 4.73; 95% CI, 1.37-16.39). CONCLUSIONS: Nearly half of the general population with chronic venous disease deteriorated during 13 years, and almost one third with varicose veins developed skin changes of CVI, increasing their risk of ulceration. Age, family history of varicose veins, history of deep venous thrombosis, overweight, and superficial reflux, especially in the small saphenous vein and with deep reflux, might influence the risk of progression. PMID- 26993677 TI - Assessment of thrombotic adverse events and treatment patterns associated with varicose vein treatment. AB - OBJECTIVE: This retrospective study assessed varicose vein treatment patterns and associated thrombotic complications in a real-world setting. METHODS: A retrospective study was conducted with health care claims data from Truven Health, covering more than 40 million insured lives per year and representing all U.S. census regions. The study sample included subjects aged >= 18 years with a new diagnosis of varicose veins who had received at least one invasive treatment (eg, surgery, endovenous thermal ablation [radiofrequency or laser], or sclerotherapy [liquid or foam]). The adverse events of interest included a coded diagnosis of deep venous thrombosis (DVT) or pulmonary embolism within 30 days of a claim for invasive treatment. Patients treated between January 1, 2008, and June 30, 2012, were observed for up to 2 years after diagnosis. RESULTS: There were 985,632 unique subjects diagnosed with varicose veins; of them, a total of 131,887 subjects met all of the study criteria: 63,033 (47.8%) having multiple therapies; 22,980 (17.4%) having laser ablation; 21,637 (16.4%) having radiofrequency ablation; 12,708 (9.6%) having sclerotherapy; and 11,529 (8.7%) having surgery. The mean age of the sample was 52.8 years, ranging from 51.5 years (surgery cohort) to 54.5 years (radiofrequency ablation cohort); 77% of the sample was female, ranging from 71% (radiofrequency ablation cohort) to 92% (sclerotherapy cohort). The mean time to treatment after diagnosis was 105 days, ranging from 75 days (sclerotherapy cohort) to 116 days (radiofrequency ablation cohort). The diagnosed prevalence (percentage of subjects within each treatment cohort) of DVT was as follows: radiofrequency ablation, 4.4%; multiple therapies- same day, 3.4%; laser ablation, 3.1%; multiple therapies--deferred, 2.6%; surgery, 2.4%; and sclerotherapy, 0.8%. For pulmonary embolism, the diagnosed prevalence was as follows: radiofrequency ablation, surgery, and laser ablation, 0.3% each; and multiple therapies--same day, multiple therapies--deferred, and sclerotherapy, 0.2% each. CONCLUSIONS: Thrombotic complications associated with invasive varicose vein treatments in the real-world setting may be higher than what has been reported in clinical trials, particularly in regard to DVT after endovenous thermal ablation therapy. A better understanding of these patterns of adverse events may have an impact on new strategies to safely and effectively manage patients with varicose veins. PMID- 26993678 TI - Outcomes and predictors of failure of thrombolysis for iliofemoral deep venous thrombosis. AB - BACKGROUND: Catheter-directed thrombolysis (CDT) with adjunctive mechanical techniques, when successful, is reported to alleviate symptoms of acute iliofemoral deep venous thrombosis (IFDVT) and to lower the occurrence of the post-thrombotic syndrome (PTS). This study aimed to determine longer term outcomes of catheter-based interventions for IFDVT and to identify predictors of immediate and mid-long-term failures that would guide optimal patient selection. METHODS: Consecutive patients who underwent CDT or pharmacomechanical thrombolysis for IFDVT between May 2007 and March 2013 were identified from a prospectively maintained database. Assessment of predictors of immediate periprocedural failure was based on the degree of clot lysis (<= 50% vs >50%) and 30-day recurrence of DVT. Long-term anatomic and clinical failures and outcomes were assessed by ultrasound imaging of the lysed segments and Villalta score (>= 5 vs <5). Survival analysis was used to assess primary patency and PTS morbidity. Multivariate binary logistic and Cox regression models were used to determine predictors of anatomic and clinical failures. RESULTS: During the study period, 93 patients (118 limbs; mean age, 49.4 +/- 16.2 years; 47 women) with symptoms averaging 11.1 +/- 9.6 days in duration were treated with various combinations of CDT or pharmacomechanical thrombolysis; in 52 (56%), at least one iliocaval stent was deployed. Immediate treatment failure was seen in 11 patients (12%) predicted by the preoperative indication "phlegmasia" (odds ratio, 3.12; P = .042) and recent surgery (odds ratio, 19.6; P = .018). At a mean ultrasonographic follow-up of 16 +/- 14 months (range, 1-65 months), six more patients sustained a rethrombosis, accounting for an overall 3-year primary patency of 72.1%. In the long-term model, loss of primary patency was associated with recent surgery (hazard ratio [HR], 4.04; P = .023), malignant disease (HR, 6.75; P = .016), and incomplete thrombolysis (<= 50%) (HR, 5.83; P < .001). By stratification of PTS on the basis of postprocedure failures, at 2 years PTS occurred in 50.6% of patients and in 16.3% of patients without failure (P < .001). CONCLUSIONS: Thrombolysis for symptomatic IFDVT can achieve high rates of thrombus resolution and reduce long-term PTS morbidity on careful patient selection. Improved anatomic and clinical outcomes are associated with the completeness of thrombolysis. PMID- 26993679 TI - The natural history and treatment outcomes of symptomatic ovarian vein thrombosis. AB - BACKGROUND: Information on ovarian vein thrombosis (OVT) is limited to some retrospective studies. The purpose of this prospective study was to evaluate the natural history and treatment outcomes of OVT. METHODS: Patients with documented symptomatic OVT who were treated with anticoagulation and had at least 3 months of follow-up were included. Outcomes of interest were recanalization rates, pain resolution, pelvic congestion syndrome, recurrent deep venous thrombosis (DVT), and mortality. All patients underwent clinical examination and duplex ultrasound; computed tomography venography was selectively performed. RESULTS: There were 23 women with a mean age of 44 years (range, 23-68 years). Fifteen (65%) right, 5 (22%) left, and 3 (23%) bilateral OVTs were detected. The median follow-up was 27 months (range, 3 months-7 years). The most common presentation was abdominal pain in nine patients (39%), followed by flank pain in six (26%). Two patients (9%) presented with dyspnea due to pulmonary embolism. The most prevalent condition was the puerperium (n = 9; 39%). Complete recanalization occurred in 16 veins (61%), partial recanalization in four veins (15%), and occlusion in six veins (24%) while patients were receiving anticoagulation. Four patients (17%) had lower extremity DVT during follow-up after the interruption of anticoagulation. Three patients (13%) developed pelvic congestion syndrome. All four deaths (17%) were due to cancer-related complications. CONCLUSIONS: Symptomatic OVT is rare. Patients fare well with anticoagulation; complete recanalization occurs in about two thirds of the patients. Recurrent DVT is found in lower extremity veins after the interruption of anticoagulation in 17% of patients; mortality was seen only in cancer patients. PMID- 26993680 TI - Tumescent technique without epinephrine for endovenous laser therapy and serum lidocaine concentration. AB - OBJECTIVE: Endovenous laser therapy (EVLT) requires tumescent lidocaine anesthesia. Although it is well known that the absorption of local anesthetic varies according to the injection site, little evidence exists establishing the maximum recommended safe dose for extravascular injections such as those used for EVLT. The aim of this study was to evaluate plasma concentration of lidocaine over time after administration of tumescent lidocaine during EVLT procedures in healthy volunteers. METHODS: Between January 2011 and February 2013, 10 healthy patients scheduled for an EVLT procedure performed in a hospital setting were recruited to participate in an observational study. For each subject, a total of 10 venous samples were obtained for analysis after surgical injection of the tumescent lidocaine solution (0.1% concentration). Samples were collected at baseline (before the surgical procedure start) and then every 30 minutes for the first 2 hours after the initial lidocaine injection. Thereafter, venous samples were obtained every 2 hours, with the last sample drawn 12 hours after the surgeon's initial lidocaine injection. All specimens were drawn from a dedicated intravenous catheter, immediately placed in a heparinized blood collection tube, and centrifuged for 10 minutes at 3000 rpm. Plasma was then removed with a pipette and stored at -70 degrees C until analyzed. Total and free plasma lidocaine concentrations were determined by immunoassay. Plasma lidocaine concentrations were normalized by peak concentration for statistical comparisons. RESULTS: Laboratory data were available for nine of the 10 volunteers. The mean total lidocaine dose administered was 6.38 (+/- 2.2) mg/kg (range, 3.57-10.7 mg/kg). The total lidocaine blood levels ranged from 0.48 (+/- 0.28) to 1.3 (+/- 0.49) mcg/mL. The free lidocaine blood levels ranged from nondetectable to 0.76 (+/- 0.43) mcg/mL. The average total time of injection for the group was 32.8 (+/ 10.0) minutes (range, 21-49 minutes). Among all dose ranges, both total and free lidocaine peak blood level ratios occurred at times 60 to 120 minutes (P < .05). No value considered in the statistical analysis exceeded 5 mcg/mL at any time. CONCLUSIONS: Tumescent lidocaine without epinephrine for EVLT procedures produces a peak serum concentration at 60 to 120 minutes. The peak plasma concentration as observed with the standard institutional dosing of tumescent lidocaine appeared below the threshold for human toxicity. PMID- 26993682 TI - Utility of iliac vein stenting in elderly population older than 80 years. AB - BACKGROUND: The geriatric population aged 80 years and older with severe manifestations of chronic venous disease face diminishing therapeutic options. Self-applied compression is often not possible because of frailty or arthritis. Significant limb swelling diminishes mobility, affects independent living, and precipitates institutionalization. Limb ulceration and pain diminish quality of life at a time when it is paramount. Cellulitis uniquely poses septicemic risk in this age group. Family caregivers are often able to continue home care if the intensity of care can be reduced. Iliac vein stenting may have a role as it appears to be safe and effective in this advanced stage of life. METHODS: Patients who had failed to respond to compression and desired palliation of continuing severe chronic venous disease symptoms were considered for iliac vein stenting. Intravascular ultrasound-guided stenting was carried out under fluoroscopy without venography in case of allergy to contrast material or decreased renal function. General anesthesia was used for better cardiopulmonary control. RESULTS: A total of 107 limbs (12 bilateral) were treated with iliac vein stents during a 13-year period, representing 5% of all stented limbs. Median age was 83 years (80-96 years), and 10 were >= 90 years; 59% were post thrombotic. Clinical, etiologic, anatomic, and pathologic classification was as follows: C2 (with pain), 3%; C3, 32%; C4, 33%; C5, 5%; and C6, 27%. Concurrent saphenous ablation was carried out in 28% when saphenous reflux was considered ancillary and not the main disease. There was no mortality. Reintervention was required in 20% of limbs for nonocclusive stent malfunction; 2% of stents occluded. Primary and primary-assisted duplex patency rates at 5 years were 52% and 90%, respectively. The visual analog scale score of pain improved from median 4 (0-9) to 0 (0-10) after stenting (P < .0001). Pain was completely relieved in 43% of limbs. Cumulative improvement in the pain score of at least 3 points was 71% at 6 years. Swelling (grade 0, none; grade 1, pitting; grade 2, ankle edema; grade 3, gross) improved from median 3 (0-3) to 1 (0-3) (P < .0001). Swelling completely resolved in 25% of limbs. Cumulative improvement of at least one grade of swelling (examination) was 63% at 6 years; 70% of limbs (n = 33) with prior cellulitis were relieved of recurrence after stent placement; 61% of active ulcers healed, and 37% of patients were able to discard stockings (P < .001). CONCLUSIONS: Iliac vein stenting appears to offer a safe and effective option in octogenarians and nonagenarians when compression fails, is difficult, or is impossible. PMID- 26993681 TI - Postoperative hemodynamic changes after endovenous laser ablation and phlebectomy in varicose vein surgery. AB - OBJECTIVE: This study was designed to examine postoperative venous hemodynamic changes at 1 and 6 months after endovenous laser ablation (EVLA) and phlebectomy for primary great saphenous varicose veins. METHODS: We retrospectively analyzed 116 limbs from 102 patients who were treated with EVLA from 2011 to 2013 at Samsung Medical Center. Venous hemodynamic changes were evaluated by air plethysmography preoperatively and at 1 month and 6 months postoperatively. The measured hemodynamic changes included venous volume (VV), venous filling index (VFI), residual volume fraction (RVF), and ejection fraction (EF). RESULTS: The study included 52 limbs from men (44.8%) and 64 limbs from women (55.2%; male/female ratio, 1:1.23). The mean age of the patients was 54.8 +/- 12.3 years. The preoperative median values were VV of 99.1 mL, VFI of 3.6 mL/s, RVF of 39.2%, and EF of 55.5%. The 1-month and 6-month postoperative median values were VV of 77.6 and 75.5 mL, VFI of 1.4 and 1.5 mL/s, RVF of 32.5% and 26.4%, and EF of 60.5% and 66.2%, respectively. The postoperative reduction rates between preoperative and 1-month measurements for VV, VFI, and RVF were 18.6%, 63.9%, and 22.2%, and the increase in EF was 7.9%. (P < .001, P < .001, P < .001, P = .043). Comparing 1-month and 6-month measurements, the reduction rates of VV and RVF were 1.9% and 15%, and the increase rates of VFI and EF were 3.2% and 7.6%, respectively. EF was significantly increased at 6 months compared with 1 month after EVLA (P = .013), but the other parameters showed no statistically significant differences between 1 month and 6 months after EVLA. CONCLUSIONS: This study demonstrated that the venous hemodynamic parameters of primary varicose veins improved after performance of EVLA and phlebectomy. PMID- 26993684 TI - Prosthetic venous valve patient selection by validated physics-based computational models. AB - BACKGROUND: There is significant interest in a venous prosthesis to replace insufficient valves. The aim of the current study was to select the patients with hemodynamic conditions most likely to benefit from a valve implant. The hypothesis is that the venous valve prosthesis is most suitable for patients with significant reflux, such as in chronic venous insufficiency (CVI), right heart hypertrophy (RHH), and right heart failure (RHF). Conversely, a prosthetic valve is likely to be of least benefit for deep venous thrombosis (DVT) patients with low flow. METHODS: To address this hypothesis, fully coupled fluid and solid mechanics computational models were developed and validated in five acute canine implants. The animal-validated simulations were then carried out for the CVI, RHH, RHF, and DVT patients based on literature hemodynamic data. A mechanical stress ratio of leaflet wall stress to fluid wall shear stress was defined to combine the effects of both fluid mechanics and solid mechanics on leaflet function, for which a lower stress ratio is hemodynamically desirable. RESULTS: The simulation results of mean valve flow velocity and percentage valve opening were found to be within 10% of the measurements in canines. The simulations show that the patients in the CVI classes 4 to 6, RHH patients, and RHF patients may have a significant reduction in stress ratio with virtual implant of a prosthetic valve. The DVT patient simulations demonstrate a minimal reduction in the stress ratio. After thrombus removal where flow is restored, however, the prosthetic valve may be helpful for post-thrombotic patients. CONCLUSIONS: For patient selections of the venous valve prosthesis, the most suitable patients are the CVI classes 4 to 6, RHH, and RHF patients. The least suitable patients are the DVT patients because a valve is not effective under low-flow conditions. The present study demonstrates a physics-based approach to patient selection that can be tested in future clinical trials. PMID- 26993685 TI - Histologic findings after mechanochemical ablation in a caprine model with use of ClariVein. AB - OBJECTIVE: The use of foam and liquid sclerotherapy for the treatment of varicose veins and underlying venous reflux is widespread. A novel device, the ClariVein Occlusion Catheter (Vascular Insights LLC, Madison, Conn), has been the subject of several clinical trials in humans. We report the initial histologic results obtained with use of the device in a caprine vein model. METHODS: A total of 11 male goats (12 veins) underwent minimally invasive procedures. Unilateral mechanochemical ablation of the lateral saphenous vein by the ClariVein Occlusion Catheter with an E-140 degrees tip was performed under fluoroscopic guidance in five veins with 5 mL of 1.5% sodium tetradecyl sulfate (STS) and in one vein with 5 mL of 0.9% saline. The remaining six received injection sclerotherapy with 5 mL of 1.5% STS or 0.9% saline. All subjects were assessed with ultrasound before the procedure and intermittently afterward during a period of 12 weeks. Subsequent termination was immediately followed by necropsy and histologic examination of the treated veins. RESULTS: Complete occlusion of the lateral saphenous vein was observed in all subjects treated with ClariVein and STS, whereas complete patency was noted in all other treatment modalities. Histologic staining with hematoxylin and eosin and Masson trichrome stain revealed total fibrotic sealing with extensive collagen production in all ClariVein/STS veins. A statistical significance was observed in the difference in the number of occluded veins between subjects treated with ClariVein/STS and those treated by injection sclerotherapy (Fisher exact test, P < .01). CONCLUSIONS: The ClariVein Occlusion Catheter with 1.5% STS can be used to achieve complete mechanochemical ablation of the lateral saphenous vein in a caprine model. The evidence in this report can be used to justify the device's use for the treatment of the great saphenous vein in subsequent human clinical trials. PMID- 26993686 TI - Endovascular recanalization of iliocaval and inferior vena cava filter chronic total occlusions. AB - Inferior vena cava filter (IVCF) placement is associated with increased risk of deep venous thrombosis. This may result from filter obstruction by trapped emboli or in situ thrombosis of the IVCF, followed by caval thrombus propagation, and may be associated with significant morbidity. Here, we describe a technique and early results of endovascular recanalization of IVCF chronic total occlusions in five patients with complete chronic total occlusions of a previously implanted IVCF, the inferior vena cava, and the bilateral iliofemoral venous systems. We describe our technique of filter displacement and recanalization with balloon mounted and self-expanding stents. All patients noted sustained clinical improvement and duplex ultrasound-confirmed patency throughout follow-up. PMID- 26993683 TI - Recanalization and flow regulate venous thrombus resolution and matrix metalloproteinase expression in vivo. AB - OBJECTIVE: We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis. METHODS: In CD1 mice, we performed surgical inferior vena cava ligation (stasis thrombosis), stenosis (thrombosis with recanalization), or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution and quantified the messenger RNA and protein levels of membrane-type matrix metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at days 4, 8, and 12 after surgery. RESULTS: Despite similar initial thrombus size, the presence of ongoing blood flow (stenosis model) was associated with a 45.91% subsequent improvement in thrombus resolution at day 8 and 12.57% at day 12 compared with stasis thrombosis (ligation model). Immunoblot and real-time polymerase chain reaction analysis demonstrated a difference in MMP-2 and MMP-9 activity at day 8 between the two models (P = .03 and P = .006, respectively) as well as a difference in MT2-MMP gene expression at day 8 (P = .044) and day 12 (P = .03) and MT1-MMP protein expression at day 4 (P = .021). Histologic analyses revealed distinct areas of recanalization in the thrombi of the stenosis model compared with the ligation model as well as the recruitment of inflammatory cells, especially macrophages, and a focal pattern of localized expression of MT1 MMP and MT3-MMP proteins surrounding the areas of recanalization in the stenosis model. CONCLUSIONS: Recanalization and ongoing blood flow accelerate deep venous thrombus resolution in vivo and are associated with distinct patterns of MT1-MMP and MT3-MMP expression and macrophage localization in areas of intrathrombus recanalization. PMID- 26993687 TI - Use of computed tomography-lymphangiography with direct injection of water soluble contrast medium to identify the origin of chylous ascites. AB - Contrast lymphangiography is a useful technique to determine the site of lymphatic leakage in the patient with chylous ascites. Conventional lymphangiography with lipid-soluble contrast material carries the disadvantage of complications, such as oil emboli and lymphedema. The authors report a successful case of computed tomography (CT)-lymphangiography with direct injection of water soluble contrast medium into a lower limb lymphatic vessel to determine the site of lymphatic leakage in a pediatric patient with refractory primary chylous ascites. The patient subsequently underwent laparoscopic ligation of the leaking site and recovered well. This novel technique offers superior potential for preoperative assessment and the planning of laparoscopic repair. PMID- 26993688 TI - Internal jugular venous aneurysm. PMID- 26993689 TI - Subcutaneous cross pelvic bypass associated with occluded iliac veins. PMID- 26993690 TI - Diagnosis and treatment of the pelvic congestion syndrome. AB - BACKGROUND: Chronic pelvic pain accounts for up to 30% of outpatient gynecologic visits in the United States, potentially affecting up to 40% of the female population during their lifetime. Pelvic congestion syndrome (PCS) is defined as chronic pelvic pain resulting from reflux or obstruction of the gonadal, gluteal, or periuterine veins, sometimes associated with perineal or vulvar varices. It can also be caused by compression of the left renal vein (LRV) between the superior mesenteric artery and the aorta, also known as the nutcracker syndrome. Whereas PCS accounts for up to 30% of patients presenting with chronic pelvic pain, it is frequently underdiagnosed. We reviewed the literature to investigate the current state of the diagnosis and treatment of this disorder. METHODS: An online database search was performed with MEDLINE. MeSH headings included PCS, chronic pelvic pain, ovarian vein reflux, nutcracker syndrome, renal vein obstruction, pelvic varicosities, labial varicosities, embolization, treatment, and therapies. RESULTS: Our MEDLINE search revealed more than 3756 references to chronic pelvic pain. Specific references to PCS, pelvic chronic pain, ovarian vein reflux, nutcracker syndrome, renal vein obstruction, pelvic varicosities, labial varicosities, embolization, treatment, and therapies, however, included only 260 references. Thirty-seven references were small series including fewer than 50 patients or individual case reports documenting medical, surgical, or endovascular treatment of PCS. The majority of these papers demonstrated successful treatment of symptoms from PCS with embolization of one or both ovarian veins in addition to treatment of refluxing internal iliac vein branches. In addition, open surgery and, more recently, endovascular stenting of LRV obstruction have shown some promise in alleviating symptoms attributed to nutcracker syndrome. CONCLUSIONS: Diagnosis of PCS requires a careful history, physical examination, and noninvasive imaging. Several large case series have demonstrated the efficacy of embolotherapy in the reduction of pelvic pain; thus, it is the most favored treatment option for patients with PCS. For patients with outflow obstruction due to nutcracker syndrome, a limited number of studies have demonstrated remission of symptoms with stenting of the LRV as an alternative to open surgery. PMID- 26993691 TI - Elimination of medically unnecessary duplex venous scanning based on an established algorithm can result in significant cost savings under Medicare for the institution and the taxpayer. AB - OBJECTIVE: The utility of duplex venous scanning (DVS) for suspected deep venous thrombosis in the emergency department (ED) remains controversial. We aimed to measure potential cost savings and economic impact in our institution and nationally for unnecessary DVS in Medicare patients seen in the ED. METHODS: We have previously calculated that 15.3% of DVS studies can safely be avoided in patients with suspected deep venous thrombosis in our ED with adherence to our protocol. The Medicare database was queried for the number of DVS studies performed in the ED and charges/payments made in 2011. Cost savings at our institution and nationally by Medicare were computed with the 15.3% number. RESULTS: In the study period, 2087 DVS studies were performed in our ED across all payers; 572 Medicare patients had 249 (43%) bilateral and 323 (57%) unilateral studies. Annual savings at our institution, with use of our protocol, were estimated at $113,778. Eliminating unnecessary after-hours DVS for 306,307 Medicare beneficiaries would result in $5,285,090 savings annually. CONCLUSIONS: Increasing pressure for cost containment under a value-based payment model necessitates critical evaluation of resource utilization. Applying this schema for all noninvasive vascular tests is an opportunity for responsible management of finite resources, reducing wasteful care, and significant cost containment. PMID- 26993692 TI - Efficacy of endovenous ablation of the saphenous veins for prevention and healing of venous ulcers. AB - In many countries, endovenous ablation (EVA) has replaced surgical stripping as the preferred method of eliminating saphenous reflux in symptomatic patients. Studies have examined the success of EVA at saphenous closure and improving leg pain and edema. However, less information is available on the ability of these techniques to promote venous leg ulcer healing or to prevent recurrence. The comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR) trial identified the role of saphenous stripping in reducing the rate of ulcer recurrence after healing, supporting this procedure for Clinical, Etiologic, Anatomic, and Pathologic (CEAP) clinical class 5 and 6 patients. In patients with venous ulcers, it remains controversial whether EVA procedures provide results similar to those of saphenous stripping in clinically relevant outcomes. This review examines the evidence supporting the use of thermal or nonthermal EVA in patients with healed or active venous ulcers and saphenous insufficiency. PMID- 26993693 TI - Nonthrombotic Venous Obstructions Cause Pelvic Congestion Syndrome. PMID- 26993694 TI - Randomized Double-Blinded Study Comparing Clinical Versus Endovascular Treatment of Iliac Vein Obstruction. PMID- 26993695 TI - Hemodynamic Consequences of Deep Venous Obstructive Disease. PMID- 26993696 TI - Recurrent Deep Venous Thrombosis Is Pathologically Different From Primary Deep Venous Thrombosis: Characterization of the First Mouse Model of Recurrent Venous Thrombosis in the Inferior Vena Cava. PMID- 26993697 TI - The Diagnostic Value of the Pubic Collateral in Deep Venous Obstructive Disease. PMID- 26993698 TI - Endovascular Recanalization of the Nonmalignant Chronically Occluded Inferior Vena Cava. PMID- 26993699 TI - Matrix Metalloproteinase Profiles in Chronic Venous Ulcer Wound Fluid of Inflammatory and Granulating Venous Leg Ulcers. PMID- 26993700 TI - Blood Sampled Directly from Varicose Veins Reveals Activation of Inflammatory Processes. PMID- 26993702 TI - Equivalent Outcomes Between Ultrasound-Assisted Thrombolysis and Standard Catheter-Directed Thrombolysis for the Treatment of Acute Pulmonary Embolism. PMID- 26993701 TI - Lower Limbs Venous Kinetics and Consequent Impact on Drainage Direction. PMID- 26993703 TI - Prospective Long-Term Comparison of Anticoagulation Treatment Versus Thrombolysis in Patients With Acute Iliofemoral Thrombosis. PMID- 26993704 TI - Contrast-Enhanced Ultrasound for Thrombus Dissolution in an In Vitro Model of Acute Deep Venous Thrombosis. PMID- 26993705 TI - Prevalence and Clinical Outcome of Free-Floating Thrombus Formation in Lower Extremity Deep Veins. PMID- 26993706 TI - Novel Endovascular Grasper for Challenging Inferior Vena Cava Filter Retrieval. PMID- 26993707 TI - Is Superficial Venous Surgery in C6 Patients Justified From a Cost/Benefit Viewpoint? PMID- 26993708 TI - A Randomized Trial of Elastic Compression Systems With High and Very High Sub Bandage Pressure Values in the Prevention of Recurrence of Venous Ulceration. PMID- 26993709 TI - Variability in Compression Provided by Commercial Stockings. PMID- 26993710 TI - Vascularized Lymph Node Transfer for Lymphedema: Anatomic Comparison of the Supraclavicular and Thoracodorsal Lymph Node Flaps. PMID- 26993711 TI - The Effect of Obesity on Long-Term Outcomes After Ultrasound-Guided Foam Sclerotherapy. PMID- 26993712 TI - Venous Drainage in Controls and Patients With Chronic Venous Insufficiency. PMID- 26993713 TI - Factors That Influence Immediate Perforator Vein Closure Rates With Radiofrequency Ablation, Laser Ablation, or Foam Sclerotherapy. PMID- 26993714 TI - Three-Year Follow-Up of First Human Use of Cyanoacrylate Adhesive for Treatment of Saphenous Vein Incompetence. PMID- 26993715 TI - One-Year Outcome of Endovenous Micropulsed Laser Ablation for Incompetent Great Saphenous Vein. PMID- 26993716 TI - The Impact of Race on Advanced Chronic Venous Insufficiency. PMID- 26993717 TI - Real-Time Visualization of Lymphatic Dysfunction in Venous Ulcer Patients. PMID- 26993718 TI - Creation and Validation of a Condition-Specific Venous Thromboembolism Risk Assessment Tool for Open Ventral Hernia Repair Patients. PMID- 26993719 TI - The Bull's-Eye Sign and Other Femoral and Suprainguinal Venographic Findings in Patients with Chronic Venous Stasis: A New Classification to Limit the Use of Intravascular Ultrasound. PMID- 26993720 TI - Increasing the Diagnostic Sensitivity of Noninvasive Imaging Techniques Before and After Iliac Vein Stenting. PMID- 26993721 TI - The Short-term Outcomes of Neovalve Deep Venous Reconstructive Surgery. PMID- 26993722 TI - Effects of Venous Stent Placement on Cutaneous Microvascular Function in Iliocaval Venous Obstruction. PMID- 26993723 TI - Reintervention in Patients Undergoing Iliofemoral Venous Stenting. PMID- 26993725 TI - Iliac Vein and Inferior Vena Cava Stenting: Experience With Post-thrombotic Obstruction Causing C5/C6 Leg Ulceration. PMID- 26993724 TI - Predictors of D-Dimer Utilization in Patients Presenting With Limb Swelling in a High-Volume Tertiary Care Center. PMID- 26993726 TI - Accuracy of Venous Thromboembolism Assessment and Compliance to Prophylaxis. PMID- 26993727 TI - Outcomes of Ultrasonic Accelerated Thrombolysis for Inferior Vena Cava Thrombosis. PMID- 26993728 TI - Hybrid Operative Thrombectomy for the Treatment of Symptomatic Iliofemoral Deep Venous Thrombosis: Initial Experience and Midterm Results. PMID- 26993729 TI - Use of Compression Stockings in Chronic Venous Disease: Validation of a New Device to Assess Patient Compliance. PMID- 26993731 TI - Patterns of Pediatric Venous Insufficiency. PMID- 26993730 TI - The Visible Lymphatic Vessels of the Lower Extremities: A Preliminary Study by Contrast Ultrasonography. PMID- 26993732 TI - Quantifying Saphenous Recirculation in Patients With Superficial Venous Insufficiency. PMID- 26993737 TI - Processing of Alcohol-Related Health Threat in At-Risk Drinkers: An Online Study of Gender-Related Self-Affirmation Effects. AB - AIMS: Defensiveness in response to threatening health information related to excessive alcohol consumption prevents appropriate behaviour change. Alternatively, self-affirmation may improve cognitive-affective processing of threatening information, thus contributing to successful self-regulation. METHODS: Effects of an online self-affirmation procedure were examined in at-risk university student drinkers. Participants were randomly assigned to a self affirmation (writing about personally relevant values) or control task (writing about values relevant to another person) prior to presentation of alcohol-related threatening information. Assessment of prosocial feelings (e.g. 'love') after the task served as a manipulation check. Generic and personalized information regarding the link between alcohol use and cancer was presented, followed by assessment of perceived threat, message avoidance and derogation. Page dwell times served as indirect indices of message engagement. Alcohol consumption and intention to drink less were assessed during the first online session and at 1 week and 1-month follow-up. RESULTS: Although self-affirmation resulted in higher levels of prosocial feelings immediately after the task, there was no effect on behaviour in the self-affirmation group. Effects on intention were moderated by gender, such that men showed lower intention immediately after self-affirmation, but this increased at 1-week follow-up. Women's intention to reduce consumption in the self-affirmation group reduced over time. Trend-level effects on indices of derogation and message acceptance were in the predicted direction only in men. CONCLUSION: It is feasible to perform self-affirmation procedures in an online environment with at-risk drinkers. However, use of internet-based procedures with this population may give rise to (gender-dependent) effects that are substantially diluted compared with lab-based experiments. PMID- 26993738 TI - Detection of OXA-48-like and NDM carbapenemases producing Klebsiella pneumoniae in Jordan: A pilot study. AB - Little is known of carbapenemase producing Klebsiella pneumoniae (CPK) in Jordan. This study aimed to determine the prevalence of CPK in a major hospital in Amman, Jordan in 2012-2013 and to characterize the isolates and detect the types of carbapenemase(s) they produced. For the 296 isolates investigated, species identification and antimicrobial susceptibilities were determined (Vitek II, bioMerieux). Isolates with decreased ertapenem susceptibility were tested for carbapenemase production using the Modified Hodge Test. Isolates with a carbapenemase-positive phenotype were characterized further via multiplex PCRs for extended-spectrum beta-lactamase and carbapenemase genes and by Pulsed Field Gel Electrophoresis (PFGE). Seven of 296 K. pneumoniae isolated in 2012-2013 (2.4%) were carbapenemase producers, five produced class D carbapenemases (OXA-48 like) and two produced a NDM metallo-beta-lactamase. All seven isolates also encoded CTX-M enzymes; CTX-M-1-like enzymes were detected in five isolates (two co-producing NDM enzymes and three co-producing OXA-48-like enzymes), CTX-M-9 was found in the two remaining OXA-48-like producers. PFGE revealed five genetically distinct types amongst the seven carbapenemase producing K. pneumoniae, with two pairs of identical isolates associated with patients treated on the same wards. The emergence of OXA-48-like and NDM carbapenemases associated with multi-drug resistant (MDR) isolates in Jordan is concerning. The strict implementation of infection control practices will help to disrupt the spread of MDR carbapenemase producers in Jordanian hospitals. PMID- 26993739 TI - Top-Down Processes Override Bottom-Up Interference in the Flanker Task. AB - Distractor interference in the flanker task is commonly viewed as an outcome of unintentional, involuntary processing, a by-product of attention-controlled processing of the target. An important implication of this notion is that the distractors are not subjected to top-down processing of their own. We tested this idea in a modified version of the flanker task, in which letter targets (S or O) were sometimes flanked by ambiguous distractors (a character that could be S or 5 or one that could be O or 0). Distractor interference was dependent on participants' expectations regarding the category of the distractors (i.e., letters or digits). For example, the O-0 distractor interfered with responding to S when it was perceived as a letter, but not when it was perceived as a digit. Hence, participants applied top-down processing to the peripheral distractors independently of the top-down processing applied to the targets. The fact that to be-ignored peripheral distractors were processed to such a high level raises questions regarding the fundamental differences between target and distractor processing, and the quality of attentional filtering. PMID- 26993740 TI - On the Necessity of Distinguishing Between Unintentional and Intentional Mind Wandering. AB - In recent years, there has been an enormous increase in the number of studies examining mind wandering. Although participants' reports of mind wandering are often assumed to largely reflect spontaneous, unintentional thoughts, many researchers' conceptualizations of mind wandering have left open the possibility that at least some of these reports reflect deliberate, intentional thought. Critically, however, in most investigations on the topic, researchers have not separately assessed each type of mind wandering; instead, they have measured mind wandering as a unitary construct, thereby conflating intentional and unintentional types. We report the first compelling evidence that an experimental manipulation can have qualitatively different effects on intentional and unintentional types of mind wandering. This result provides clear evidence that researchers interested in understanding mind wandering need to consider the distinction between unintentional and intentional occurrences of this phenomenon. PMID- 26993741 TI - Does Causality Matter More Now? Increase in the Proportion of Causal Language in English Texts. AB - The vast majority of the work on culture and cognition has focused on cross cultural comparisons, largely ignoring the dynamic aspects of culture. In this article, we provide a diachronic analysis of causal cognition over time. We hypothesized that the increased role of education, science, and technology in Western societies should be accompanied by greater attention to causal connections. To test this hypothesis, we compared word frequencies in English texts from different time periods and found an increase in the use of causal language of about 40% over the past two centuries. The observed increase was not attributable to general language effects or to changing semantics of causal words. We also found that there was a consistent difference between the 19th and the 20th centuries, and that the increase happened mainly in the 20th century. PMID- 26993742 TI - Letter to the Editor Re: Merger of models on clinical instability - Misleading for patients and clinicians. PMID- 26993744 TI - Synthesis of E. faecium wall teichoic acid fragments. AB - The first synthesis of different Enterococcus faecium wall teichoic acid (WTA) fragments is presented. The structure of these major cell wall components was elucidated recently and it was shown that these glycerolphosphate (GroP) based polymers are built up from -6-(GalNAc-alpha(1-3)-GalNAc-beta(1-2)-GroP)- repeating units. We assembled WTA fragments up to three repeating units in length, in two series that differ in the stereochemistry of the glycerolphosphate moiety. The key GalNAc-GalNAc-GroP synthons, required for the synthesis, were generated from galactosazide building blocks that were employed in highly stereoselective glycosylation reactions to furnish both the alpha- and beta configured linkages. By comparing the NMR spectra of the synthesized fragments with the isolated material it appears that the hereto undefined stereochemistry of the glycerol phosphate moiety is sn-glycerol-3-phosphate. The generated fragments will be valuable tools to study their immunological activity at the molecular level. PMID- 26993743 TI - Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm. AB - Many conditions culminate in heart failure (HF), a multi-organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence-base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite. PMID- 26993746 TI - Modeling Hematopoiesis and Responses to Radiation Countermeasures in a Bone Marrow-on-a-Chip. AB - Studies on hematopoiesis currently rely on animal models because in vitro culture methods do not accurately recapitulate complex bone marrow physiology. We recently described a bone marrow-on-a-chip microfluidic device that enables the culture of living hematopoietic bone marrow and mimics radiation toxicity in vitro. In the present study, we used this microdevice to demonstrate continuous blood cell production in vitro and model bone marrow responses to potential radiation countermeasure drugs. The device maintained mouse hematopoietic stem and progenitor cells in normal proportions for at least 2 weeks in culture. Increases in the number of leukocytes and red blood cells into the microfluidic circulation also could be detected over time, and addition of erythropoietin induced a significant increase in erythrocyte production. Exposure of the bone marrow chip to gamma radiation resulted in reduction of leukocyte production, and treatment of the chips with two potential therapeutics, granulocyte-colony stimulating factor or bactericidal/permeability-increasing protein (BPI), induced significant increases in the number of hematopoietic stem cells and myeloid cells in the fluidic outflow. In contrast, BPI was not found to have any effect when analyzed using static marrow cultures, even though it has been previously shown to accelerate recovery from radiation-induced toxicity in vivo. These findings demonstrate the potential value of the bone marrow-on-a-chip for modeling blood cell production, monitoring responses to hematopoiesis-modulating drugs, and testing radiation countermeasures in vitro. PMID- 26993745 TI - Discovery of novel N,N-3-phenyl-3-benzylaminopropionanilides as potent inhibitors of cholesteryl ester transfer protein in vivo. AB - Epidemiological studies have identified that the risk of cardiovascular events increases due to the decreased levels of high density lipoprotein-cholesterol and the elevated levels of low density lipoprotein-cholesterol. Herein, we report a novel series of N,N-3-phenyl-3-benzylaminopropionanilide derivatives, which were identified as potent cholesteryl ester transfer protein (CETP) inhibitor. The initial lead compound L10 (IC50 8.06 MUM) was found by pharmacophore-based virtual screening (Dong-Mei Zhao et al., Chin. Chem. Lett.2014, 25, 299). After systematic structure variation and biological testing against CETP, two different series were identified as scaffolds for potent CETP inhibitors. One is N,N-3 phenyl-3-benzylaminopropanamide derivatives, which were investigated in our previous paper (Bioorg. Med. Chem.2015, doi: http://dx.doi.org/10.1016/j.bmc.2015.12.010). The most potent compound HL16 in that series has the IC50 of 0.69 MUM. The other series is N,N-3-phenyl-3 benzylaminopropionanilide derivatives, which was investigated in current study. Further optimization of the structure-activity relationship (SAR) resulted in H16 (IC50 0.15 MUM), which was discovered as a potent CETP inhibitor in vitro by BODIPY-CE fluorescence assay. In addition, the results of pharmacodynamics studies showed that H16 exhibited both favorable HDL-C enhancement and LDL-C reduction in vivo by hamster. It also has an excellent stability in rat liver microsomal. PMID- 26993747 TI - Cholesterol homeostasis: How do cells sense sterol excess? AB - Cholesterol is vital in mammals, but toxic in excess. Consequently, elaborate molecular mechanisms have evolved to maintain this sterol within narrow limits. How cells sense excess cholesterol is an intriguing area of research. Cells sense cholesterol, and other related sterols such as oxysterols or cholesterol synthesis intermediates, and respond to changing levels through several elegant mechanisms of feedback regulation. Cholesterol sensing involves both direct binding of sterols to the homeostatic machinery located in the endoplasmic reticulum (ER), and indirect effects elicited by sterol-dependent alteration of the physical properties of membranes. Here, we examine the mechanisms employed by cells to maintain cholesterol homeostasis. PMID- 26993748 TI - Prevalence of abdominal obesity in adolescents: association between sociodemographic factors and lifestyle. AB - OBJECTIVE: To estimate the prevalence of abdominal obesity and verify the association with sociodemographic factors (gender, school shift, ethnicity, age, maternal education and economic status) and lifestyle (alcohol consumption, sleep, soft drink consumption, level of physical activity and sedentary behavior) in adolescents in Southern Brazil. METHODS: This was a cross-sectional epidemiological study of 930 adolescents (490 girls) aged 14 to 19 years, living in the city of Sao Jose, SC, Brazil. A self-administered questionnaire was used to collect sociodemographic and lifestyle data. Abdominal obesity was measured through the waist circumference and analyzed according to gender and age. Descriptive statistics (absolute and relative frequency, mean and standard deviation) and binary logistic regression, expressed as odds ratios (OR) and 95% confidence interval (95%CI) were employed, with p<0.05 being considered statistically significant; the SPSS 17.0 software was used for the statistical analyses. RESULTS: The prevalence of abdominal obesity was 10.6% for the total sample (10.5% male, 10.8% female). Adolescents that watched television daily for two or more hours (OR=2.11, 95%CI 1.08 to 4.13) had a higher chance of having abdominal obesity and adolescents whose mothers had fewer than eight years of schooling (OR=0.56; 95%CI from 0.35 to 0.91) had a lower chance of having abdominal obesity. CONCLUSIONS: Approximately one in 10 adolescents had abdominal obesity; the associated factors were maternal schooling (>=8 years) and television screen time (>=2hours/day). PMID- 26993749 TI - Influence of the uncertainty in the validation of PBPK models: A case-study for PFOS and PFOA. AB - Physiologically-based pharmacokinetic (PBPK) models are mathematical representations of the human body aimed at describing the time course distribution of chemicals in human tissues. Since parameterization of PBPK models is based on empirical estimation and experimental data, simulation results may have high degree of uncertainty. As a consequence, the reliability of model validation is highly affected. In this study, the parametric uncertainty associated with PBPK models developed for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were analyzed and the different validation approaches were discussed for a case-study in Tarragona County (NE of Spain). Physicochemical parameters and dietary intake of PFOS and PFOA were estimated from previous investigations performed in Tarragona County. A sensitivity analysis (SA) was performed to understand the degree of influence of input parameters on the final outcomes. The uncertainty of the PBPK models' outcome was assessed by propagating the parametric uncertainty using the Latin Hypercube Sampling (LHS) technique. The elimination constants (Tm and Kt) as well as the Free fraction and the Intake, were the most influential parameters according to the SA results, being up to 83% for PFOS and 99.9% for PFOA. The validation of the PBPK model, which was performed using different approaches, showed clear discrepancies in the visual validation when compared with the statistical analysis. PMID- 26993750 TI - Investigation of developmental toxicity and teratogenicity of cyclosporine A, tacrolimus and their combinations with prednisolone. AB - In this study, it was aimed to investigate the toxic and teratogenic effects of cyclosporine A and tacrolimus and their combinations with prednisolone using an in vitro rat embryo culture technique. Cyclosporine A (4-40 MUg/ml), tacrolimus (1-20 MUg/ml) and combinations of these drugs with prednisolone (20 MUg/ml) at different concentrations were tested. Cyclosporine A and its combination with prednisolone were determined to have toxic effects on embryonic growth after 10 MUg/ml. When used alone, the lowest dose of tacrolimus had embryotoxic effects on the total morphological score and number of somites. It was determined that cyclosporine A caused hematoma at 4 MUg/ml and higher doses, and tacrolimus especially at 20 MUg/ml caused an open neural tube beside hematoma. It was observed that cyclosporine A at 40 MUg/ml dose initiated apoptotic effects at a very low rate, prednisolone increased this effect, tacrolimus led to excessive apoptosis after 15 MUg/ml, and this effect did not change with prednisolone supplement. We are of the opinion that the doses should be determined carefully when cyclosporine A and tacrolimus are required to be administered to pregnant women with prednisolone combination, as prednisolone increases the toxic effects of cyclosporine A, and increases teratogenic effects of tacrolimus. PMID- 26993751 TI - Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats. AB - Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. PMID- 26993752 TI - Increasing tumor length is associated with regional lymph node metastases and decreased survival in esophageal cancer. AB - BACKGROUND: Although tumor length has received little attention for staging of esophageal cancer, it may be a valid prognostic feature for node positivity and survival. METHODS: Through retrospective review of a prospective institutional database, esophageal cancer patients who completed esophagectomy without neoadjuvant chemoradiation were analyzed. Pathologic tumor lengths were compared with node positivity and survival through a zero-inflated negative binomial regression model and multivariable Cox proportional hazards model, respectively. RESULTS: Between January 2000 and July 2015, 98 patients met inclusion, criteria (84% male, median age of 65, 90% adenocarcinoma). Median tumor length was 2.5 cm with each 1-cm increase in length increasing the odds of node positivity (odds ratio 3.55, 95% confidence interval 1.50 to 8.40, P = .004) and decreasing overall survival (hazards ratio 1.18, 95% confidence interval 1.06 to 1.32, P < .003). CONCLUSION: This study suggests an association among tumor length, lymph node metastasis, as well as overall survival in esophageal cancer patients who have not received neoadjuvant chemoradiotherapy. PMID- 26993753 TI - Treating psoriasis by targeting its susceptibility gene Rel. AB - Psoriasis is a chronic inflammatory disorder of the skin. Accumulating evidence indicates that the Rel gene, a member of the NF-kappaB family, is a risk factor for the disease. We sought to investigate whether psoriasis can be prevented by directly targeting the Rel gene transcript, i.e., the c-Rel mRNA. Using chemically-modified c-Rel specific siRNA (siRel) and poly(ethylene glycol)-b poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) micelles, we successfully knocked down the expression of c-Rel, and showed that the expression of cytokine IL-23, a direct target of c-Rel that can drive the development of IL-17-producing T cells, was markedly inhibited. More importantly, treating mice with siRel not only prevented but also ameliorated imiquimod (IMQ)-induced psoriasis. Mechanistic studies showed that siRel treatment down-regulated the expression of multiple inflammatory cytokines. Taken together, these results indicate that the susceptibility gene Rel can be targeted to treat and prevent psoriasis. PMID- 26993755 TI - Atrial Rhabdomyoma Resection With Extracellular Matrix Reconstruction of the Right Atrial Free Wall in an Infant. AB - A neonate was diagnosed with a mediastinal mass after presenting with bradycardia. At surgery, she was found to have a 4-cm mass replacing most of the right atrial free wall. After tumor resection, the right atrium was reconstructed with an extracellular matrix biomaterial that supports native tissue regeneration. Her pathology revealed rhabdomyoma, which is rare in patients without tuberous sclerosis. The procedure was well tolerated but was complicated by narrowing of the superior vena cava that required dilation postoperatively. PMID- 26993754 TI - Construction and phenotypic characterization of M68, an RruI quorum sensing knockout mutant of the photosynthetic alphaproteobacterium Rhodospirillum rubrum. AB - Many bacterial species communicate using a complex system known as quorum sensing (QS) in which gene expression is controlled in response to cell density. In this study an N-acylhomoserine lactone (AHL) synthase (Rru_A3396) knockout mutant (M68) of Rhodospirillum rubrum S1H (WT) was constructed and characterized phenotypically under light anaerobic conditions. Results showed that R. rubrum WT produces unsubstituted, 3-OH and 3-oxo-substituted AHLs with acyl chains ranging from 4 to 14 carbons, with 3-OH-C8 being the most abundant. Growth, pigment content and swimming motility were found to be under the control of this LuxI type QS system. In addition, cultivation in a low shear environment put forward the aggregative phenotype of M68 and linked biofilm formation to QS in R. rubrum S1H. Interestingly, QS-mutant M68 continued to produce decreased levels of 3-OH C8-HSL, probably due to the presence of an extra HdtS-type AHL synthase. PMID- 26993756 TI - Coronary Ostioplasty for Congenital Atresia of the Left Main Coronary Artery Ostium in a Teenage Boy. AB - Atresia of the left coronary artery ostium is extremely rare. We report the case of a 13-year-old boy who played volleyball in school and collapsed with severe chest pain during practice. He was referred to our hospital, and imaging modalities showed atresia of the left main coronary artery ostium. Urgent coronary ostioplasty was performed using a patch of 0.6% glutaraldehyde-treated autologous pericardium. His postoperative course was uneventful, and he has had a normal everyday life without chest pain 8 months postoperatively. Physicians should be aware of the patient's history, as in this case, because prompt imaging diagnosis is essential when there is a high likelihood that the event is related to myocardial ischemia. Since long-term outcome is uncertain even after successful surgical revascularization, close follow-up is required. PMID- 26993757 TI - Discontinuous Pulmonary Artery. AB - We describe the diagnosis and surgical repair of a five-month-old infant with a congenital discontinuous right pulmonary artery. Initial echocardiogram failed to show the right pulmonary artery and revealed systemic left pulmonary artery pressure based on the tricuspid regurgitation jet. Computed tomographic angiography confirmed the diagnosis of discontinuous right pulmonary artery. The right pulmonary artery appeared essentially normal in size, and there were no significant aortopulmonary collateral arteries. Using cardiopulmonary bypass and aortic transection, we created an anastomosis between the right and the main pulmonary arteries augmented anteriorly by a pericardial patch. Postoperative lung perfusion scan demonstrated balanced pulmonary blood flow to the lungs. Pulmonary hypertension resolved over three weeks in the postoperative period, an expected outcome in this age-group. PMID- 26993758 TI - Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low Grade Adverse Events in Patients With CML-CP: The ENRICH Study. AB - BACKGROUND: Many patients with chronic myeloid leukemia in chronic phase experience chronic treatment-related adverse events (AEs) during imatinib therapy. These AEs can impair quality of life and lead to reduced treatment adherence, which is associated with poor clinical outcomes. PATIENTS AND METHODS: In the phase II ENRICH (Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events) study (N = 52), the effect of switching patients with imatinib related chronic low-grade nonhematologic AEs from imatinib to nilotinib was evaluated. RESULTS: Three months after switching to nilotinib, 84.6% of the patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% had resolved within 3 months of switching to nilotinib. Of evaluable patients, most had improvements in overall quality of life after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response (BCR-ABL1 <= 0.1% on the International Scale). After switching to nilotinib, the rate of the major molecular response was 76.1% at 3 months and 87.8% at 12 months. Treatment emergent AEs reported with nilotinib were typically grade 1 or 2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib because of new or worsening AEs. CONCLUSION: Overall, results from the ENRICH study demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with chronic myeloid leukemia in chronic phase, in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018. PMID- 26993760 TI - Are ENT surgeons in the UK at risk of stress, psychological morbidities and burnout? A national questionnaire survey. AB - INTRODUCTION: Work-related stress, psychological disorders and burnout are common occupational disorders affecting UK doctors. To date, there are no studies looking at these psychosocial morbidities amongst ENT surgeons worldwide. METHODS: The General Health Questionnaire-12 (GHQ-12) and abbreviated Maslach Burnout Inventory (aMBI) were incorporated into a questionnaire on occupational diseases amongst ENT surgeons and distributed to the entire membership of ENT-UK. The survey study also acquired demographic data on grade of respondent, years of experience in ENT and subspecialty interest. RESULTS: We received 108 (8.1% response rate) appropriately filled GHQ-12 and 121 (9.0% response rate) aMBI questionnaires. 61 respondents (56.5%) on the GHQ-12 were at high risk of developing stress and psychological morbidity and 35 (28.9%) had high enough aMBI scores to suggested burnout. When comparing scores of both GHQ-12 and aMBI with grade of respondent, years of experience in ENT and subspecialty, statistical difference was only found on the risk of stress and psychiatric disorders amongst paediatric ENT surgeons (7 high risk vs 0 low risk, p = 0.02), however the number of these respondents was small (7 in total). Both questionnaires had been validated for use within our population. CONCLUSION: We found high incidence rates of stress and psychological morbidity (56.5%) and a burnout prevalence rate of 28.9% amongst our responding cohort of UK Oto-rhino-laryngologists. No meaningful differences were found between stress, psychological morbidity and burnout with grade of ENT surgeon, years of experience in ENT and subspecialty within ENT. PMID- 26993759 TI - A systematic review of new treatments for cryptoglandular fistula in ano. AB - AIM: In 2007 the ACPGBI published a position statement on the management of cryptoglandular fistula in ano. Over the last seven years a number of new treatments have been developed and the aim of this systematic review was to assess their effectiveness. METHOD: A systematic review of all English language literature relevant to novel treatment strategies for cryptoglandular fistula in ano, published between 1 January 2007 and 31 Dec 2014 was carried out using MEDLINE (PubMed and Ovid), EMBASE (Ovid) and the Cochrane Library of Systematic Reviews/Controlled Trials for relevant literature. Technical notes, commentaries, letters and meeting abstracts were excluded. The different treatments were assessed with regards to fistula closure rate in relation to length of follow up and reported complications. RESULTS: Seventy potential articles published between 1 January 2007 and 31 December 2014 were identified from the initial literature search. Twenty-one articles were included for final analysis although only two were randomized controlled trials, the remainder being retrospective or prospective series. CONCLUSION: This systematic review has demonstrated that whilst there have been technological advances to treat complex cryptoglandular fistula in ano, these are in an early stage of evolution and although early results were promising they are difficult to reproduce. Longer follow up data is not currently available and these treatments should not be introduced without further evidence. PMID- 26993761 TI - Left atrial deformation and phasic function determined by 2-dimensional speckle tracking echocardiography in healthy dogs. AB - INTRODUCTION: Feasibility, intra- and inter-observer variability of measuring left atrial (LA) longitudinal strain and strain rate (SR) variables using speckle tracking echocardiography (STE) have not been reported in the dog. Reference intervals for these variables which can be useful to estimate LA function have been provided. ANIMALS: Forty-eight healthy adult dogs. MATERIALS AND METHODS: Left atrial longitudinal deformation was evaluated in each dog by STE, and different combinations of STE variables were used to describe the 3 phases (reservoir, conduit and booster pump phase) of the LA function. RESULTS: Left atrial STE was possible in 40/48 dogs (83%). Strain and SR curves in healthy dogs were characterized, and reference intervals for several strain and SR variables are provided. Intra- and inter-observer variability, expressed as percent difference between observations or observers, was 3.58%-10.8% for indices of the LA reservoir function, 10.48%-15.82% for indices of the LA conduit function and 14.1%-34% for indices of the LA contractile function. Strain rate in early diastole and strain rate at atrial contraction variables were correlated significantly with age. No other relationships (body weight, heart rate or LA size) with any STE variables could be identified. CONCLUSION: Speckle tracking echocardiography provides quantitative measurements of LA longitudinal deformation and can be used to assess LA phasic function in healthy dogs. Further studies of these variables in dogs with cardiac diseases are needed to determine the clinical applicability and utility. PMID- 26993762 TI - Photodynamic therapy using methylene blue in lung adenocarcinoma xenograft and hamster cheek pouch induced squamous cell carcinoma. AB - BACKGROUND: Photodynamic therapy (PDT) is used to treat early proximal bronchial cancer during a flexible bronchoscopy. The technique relies on the excitation of a photosensitizer by an appropriate wavelength, which is delivered into the bronchus in close contact with the tumor. OBJECTIVE: To assess methylene blue (MB) as a PDT agent for the treatment of respiratory tract cancer in animal models. METHODS: MB-induced PDT was performed on 7 subcutaneous NCI-H460 lung adenocarcinoma xenografts in nude mice and 9 induced squamous cell cancer in the hamster cheek pouch model. In mice, PDT was carried out on right-sided tumors after intratumoral injection of methylene blue 1% (w/v) and illumination at 630nm at 200J/cm (Diomed PDT 630), with the left tumor used as control (illumination alone or MB alone). The tumoral volume was assessed before and 15 days after PDT. RESULTS: Fourteen xenografts were treated in mice, including seven treated with MB-PDT, producing a 52% mean tumor volume regression (1568mm(3)vs. 544mm(3)) compared to seven control cases in which tumor volume increased (p=0.007; Mann Whitney test). Nine cheek pouch induced carcinomas were treated in the hamster group, with a mean volume decrease of 85.8% (from 44.8% to 100%) (initial mean volume=210mm(3)vs. post PDT mean volume=97mm(3)). Histology analysis showed 4/9 complete responses. CONCLUSION: Intratumoral MB appears efficient as PDT agent for cancer treatment in animal models. Further studies are needed to assess the safety and efficacy of MB-associated PDT for the treatment of lung cancer in humans. PMID- 26993763 TI - Biogeography and diversification of Brassicales: A 103million year tale. AB - Brassicales is a diverse order perhaps most famous because it houses Brassicaceae and, its premier member, Arabidopsis thaliana. This widely distributed and species-rich lineage has been overlooked as a promising system to investigate patterns of disjunct distributions and diversification rates. We analyzed plastid and mitochondrial sequence data from five gene regions (>8000bp) across 151 taxa to: (1) produce a chronogram for major lineages in Brassicales, including Brassicaceae and Arabidopsis, based on greater taxon sampling across the order and previously overlooked fossil evidence, (2) examine biogeographical ancestral range estimations and disjunct distributions in BioGeoBEARS, and (3) determine where shifts in species diversification occur using BAMM. The evolution and radiation of the Brassicales began 103Mya and was linked to a series of inter continental vicariant, long-distance dispersal, and land bridge migration events. North America appears to be a significant area for early stem lineages in the order. Shifts to Australia then African are evident at nodes near the core Brassicales, which diverged 68.5Mya (HPD=75.6-62.0). This estimated age combined with fossil evidence, indicates that some New World clades embedded amongst Old World relatives (e.g., New World capparoids) are the result of different long distance dispersal events, whereas others may be best explained by land bridge migration (e.g., Forchhammeria). Based on these analyses, the Brassicaceae crown group diverged in Europe/Northern Africa in the Eocene, circa 43.4Mya (HPD=46.6 40.3) and Arabidopsis separated from close congeners circa 10.4Mya. These ages fall between divergent dates that were previously published, suggesting we are slowly converging on a robust age estimate for the family. Three significant shifts in species diversification are observed in the order: (1) 58Mya at the crown of Capparaceae, Cleomaceae and Brassicaceae, (2) 38Mya at the crown of Resedaceae+Stixis clade, and (3) 21Mya at the crown of the tribes Brassiceae and Sisymbrieae within Brassicaceae. PMID- 26993764 TI - RAD sequencing enables unprecedented phylogenetic resolution and objective species delimitation in recalcitrant divergent taxa. AB - Species delimitations is problematic in many cases due to the difficulty of evaluating predictions from species hypotheses. In many cases delimitations rely on subjective interpretations of morphological and/or DNA data. Species with inadequate genetic resources needed to answer questions regarding evolutionary relatedness and genetic uniqueness are particularly problematic. In this study, we demonstrate the utility of restriction site associated DNA sequencing (RAD seq) to objectively resolve unambiguous phylogenetic relationships in a recalcitrant group of deep-sea corals with divergences >80 million years. We infer robust species boundaries in the genus Paragorgia by testing alternative delimitation hypotheses using a Bayes Factors delimitation method. We present substantial evidence rejecting the current morphological species delimitation model for the genus and infer the presence of cryptic species associated with environmental variables. We argue that the suitability limits of RAD-seq for phylogenetic inferences cannot be assessed in terms of absolute time, but are contingent on taxon-specific factors. We show that classical taxonomy can greatly benefit from integrative approaches that provide objective tests to species delimitation hypotheses. Our results lead the way for addressing further questions in marine biogeography, community ecology, population dynamics, conservation, and evolution. PMID- 26993765 TI - BAY 11-7085 induces glucocorticoid receptor activation and autophagy that collaborate with apoptosis to induce human synovial fibroblast cell death. AB - Inhibition of proapoptotic pathways in synovial fibroblasts is one of the major causes of synovial proliferation and hyperplasia in rheumatic diseases. We have shown previously that NF-kappaB inhibitor BAY 11-7085, through inactivation of PPAR-gamma, induces apoptosis in human synovial fibroblasts. In this work we showed that BAY 11-7085 induced autophagy that preceded BAY 11-7085-induced apoptosis. Of interest, BAY 11-7085 induced Serine 211 phosphorylation and degradation of glucocorticoid receptor (GR). Glucocorticoid prednisolone induced both activation and degradation of GR, as well as autophagy in synovial fibroblasts. BAY 11-7085-induced cell death was significantly decreased with glucocorticoid inhibitor mifepristone and with inhibitors of autophagy. Both BAY 11-7085-induced autophagy and GR activation were down regulated with PPAR-gamma agonist, 15d-PGJ2 and MEK/ERK inhibitor UO126. Inhibition of autophagy markedly decreased endogenous and BAY 11-7085-induced ERK phosphorylation, suggesting a positive feed back loop between ERK activation and autophagy in synovial fibroblasts. Co-transfection of MEK1 with PPAR-gamma1 in HEK293 cells caused known inhibitory phosphorylation of PPAR-gamma1 (Serine 112) and enhanced GR degradation, in the absence or presence of prednisolone. Furthermore, GR was both phosphorylated on Serine 211 and down regulated in synovial fibroblasts during serum starvation induced autophagy. These results showed that GR activation and PPAR-gamma inactivation mediated BAY 11-7085-induced autophagy. PMID- 26993766 TI - Implication of NPM1 phosphorylation and preclinical evaluation of the nucleoprotein antagonist N6L in prostate cancer. AB - Despite the advent of several new treatment options over the past years, advanced/metastatic prostate carcinoma (PCa) still remains incurable, which justifies the search for novel targets and therapeutic molecules. Nucleophosmin (NPM1) is a shuttling nucleoprotein involved in tumor growth and its targeting could be a potential approach for cancer therapy. We previously demonstrated that the multivalent pseudopeptide N6L binds to NPM1 potently affecting in vitro and in vivo tumor cell growth of various tumor types as well as angiogenesis. Furthermore, NPM1 binds to androgen receptor (AR) and modulate its activity. In this study, we first investigated the implication of the NPM1 and its Thr199 and Thr234/237 phosphorylated forms in PCa. We showed that phosphorylated forms of NPM1 interact with androgen receptor (AR) in nucleoplasm. N6L treatment of prostate tumor cells led to inhibition of NPM1 phosphorylation in conjunction with inhibition of AR activity. We also found that total and phosphorylated NPM1 were overexpressed in castration-resistant PCa. Assessment of the potential therapeutic role of N6L in PCa indicated that N6L inhibited tumor growth both in vitro and in vivo when used either alone or in combination with the standard-of care first- (hormonotherapy) and second-line (docetaxel) treatments for advanced PCa. Our findings reveal the role of Thr199 and Thr234/237 phosphorylated NPM1 in PCa progression and define N6L as a new drug candidate for PCa therapy. PMID- 26993767 TI - MicroRNA-630 suppresses tumor metastasis through the TGF-beta- miR-630-Slug signaling pathway and correlates inversely with poor prognosis in hepatocellular carcinoma. AB - The epithelial-mesenchymal transition (EMT) is the key process that drives tumor metastasis. Accumulating evidence suggests that the deregulation of some microRNAs (miRNAs), is implicated in this process. Here, we highlight the function and molecular mechanism of miR-630 and its potential clinical application in hepatocellular carcinoma (HCC). First, we identified the clinical relevance of miR-630 expression in a screen of 97 HCC patient tissues. Patients with low miR-630 expression had higher recurrence rates and shorter overall survival than those with high miR-630 expression. Functional studies demonstrated the overexpression of miR-630 in HCC cells attenuated the EMT phenotype in vitro. Conversely, inhibition of miR-630 promoted EMT in HCC cells. Mechanistically, our data revealed that miR-630 suppressed EMT by targeting Slug. Knockdown of Slug expression reversed miR-630 inhibitor-mediated EMT progression. Furthermore, we found that the TGF-beta-Erk/SP1 and JNK/c-Jun signaling pathways repressed miR 630 transcription through occupying transcription factor binding sites. Ectopic expression of miR-630 restored the TGF-beta-activated EMT process. Taken together, these findings demonstrate, in HCC cells, miR-630 exerts its tumor suppressor functions through the TGF-beta-miR-630-Slug axis and provides a potential prognostic predictor for HCC patients. PMID- 26993768 TI - Progression of benign prostatic hyperplasia is associated with pro-inflammatory mediators and chronic activation of prostate-infiltrating lymphocytes. AB - Benign prostatic hyperplasia (BPH) is a common chronic non-malignant condition whose prevalence substantially increases with age. Immune cell infiltration and pro-inflammatory mediators have been implicated in the pathogenesis. Here, we characterized 21 extracellular markers on prostate-infiltrating lymphocytes (PILs) and analyzed expression of 26 soluble proteins in prostate tissue obtained from BPH patients (n = 31). These data were correlated with clinical parameters and compared with peripheral blood mononuclear cells (PBMCs) (n = 10). Increased frequencies of T cells expressing co-inhibitory receptors LAG-3, PD-1, TIM-3 or CTLA-4, and co-stimulatory receptors CD28, OX40 or 4-1BB were observed in BPH tissue compared to PBMCs. These findings are consistent with chronic activation and possible functional exhaustion of PILs that may be further augmented by several identified pro-inflammatory factors, such as IL-8 and MCP-1, promoting inflammation and chemotaxis of immune cells to the prostate. Prostate size and plasma prostate-specific antigen levels positively correlated with IL-8 and MCP-1 concentrations, and frequencies of T cells expressing CTLA-4 and TIM-3. It remains to be established whether the link between inflammation and BPH progression supported by our findings reflects a progressive failure of the immune system leading to decreased immune surveillance and development of prostate cancer. PMID- 26993769 TI - Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer. AB - The JNK and P38alpha pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38alpha pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38alpha pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings. PMID- 26993770 TI - MicroRNA-16 sensitizes breast cancer cells to paclitaxel through suppression of IKBKB expression. AB - Paclitaxel (Taxol) is an effective chemotherapeutic agent for treating breast cancer patients. However, chemoresistance is a major obstacle in cancer treatment. Here, we showed that overexpression of miR-16 promoted Taxol-induced cytotoxicity and apoptosis in breast cancer cells. Furthermore, IkappaB kinase beta (IKBKB) was identified as a direct target of miR-16. Up-regulation of IKBKB suppressed Taxol-induced apoptosis and led to an increased resistance to Taxol, and restoring IKBKB expression in miR-16-overexpressing breast cancer cells recovered Taxol resistance. Moreover, miR-16 was highly expressed in Taxol sensitive breast cancer tissues compared with Taxol-resistant tissues, and there was an inverse correlation between miR-16 expression and IKBKB expression in breast cancer tissues. The expression levels of miR-16 were negatively associated with T stages, whereas the expression of IKBKB was positively correlated with T stages, lymph node metastasis and clinical stages. Taken together, our data demonstrates that miR-16 sensitizes breast cancer cells to Taxol through the suppression of IKBKB expression, and targeting miR-16/IKBKB axis will be a promising strategy for overcoming Taxol resistance in breast cancer. PMID- 26993772 TI - Small ubiquitin-related modifier 1 is involved in hepatocellular carcinoma progression via mediating p65 nuclear translocation. AB - Small ubiquitin-related modifier (SUMO) proteins participate in a post translational modification called SUMOylation and regulate a variety of intracellular processes, such as targeting proteins for nuclear import. The nuclear transport of p65 results in the activation of NF-kappaB, and p65 contains several SUMO interacting motifs (SIMs). However, the relationship between p65 and SUMO1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we demonstrated the potential roles of SUMO1 in HCC via the regulation of p65 subcellular localization. We found that either SUMO1- or p65-positive immunoreactivity was remarkably increased in the nuclei of tumor tissues in HCC patients compared with non-tumor tissues, and further analysis suggested a correlation between SUMO1- and nuclear p65-positive immunoreactivities (R = 0.851, P = 0.002). We also verified the interaction between p65 and SUMO1 in HCC by co-immunoprecipitation. TNF-alpha and hypoxia increased SUMO1 protein levels and enhanced SUMO1-modified p65 SUMOylation. Moreover, the knockdown of SUMO1 decreased p65 nuclear translocation and inhibited NF-kappaB transcriptional activity. Further the results of this study revealed that the knockdown of SUMO1 suppressed the proliferation and migration of hepatoma cells. These results suggest that SUMO1 contributes to HCC progression by promoting p65 nuclear translocation and regulating NF-kappaB activity. PMID- 26993771 TI - Immortalization capacity of HPV types is inversely related to chromosomal instability. AB - High-risk human papillomavirus (hrHPV) types induce immortalization of primary human epithelial cells. Previously we demonstrated that immortalization of human foreskin keratinocytes (HFKs) is HPV type dependent, as reflected by the presence or absence of a crisis period before reaching immortality. This study determined how the immortalization capacity of ten hrHPV types relates to DNA damage induction and overall genomic instability in HFKs.Twenty five cell cultures obtained by transduction of ten hrHPV types (i.e. HPV16/18/31/33/35/45/51/59/66/70 E6E7) in two or three HFK donors each were studied.All hrHPV-transduced HFKs showed an increased number of double strand DNA breaks compared to controls, without exhibiting significant differences between types. However, immortal descendants of HPV-transduced HFKs that underwent a prior crisis period (HPV45/51/59/66/70-transduced HFKs) showed significantly more chromosomal aberrations compared to those without crisis (HPV16/18/31/33/35 transduced HFKs). Notably, the hTERT locus at 5p was exclusively gained in cells with a history of crisis and coincided with increased expression. Chromothripsis was detected in one cell line in which multiple rearrangements within chromosome 8 resulted in a gain of MYC.Together we demonstrated that upon HPV-induced immortalization, the number of chromosomal aberrations is inversely related to the viral immortalization capacity. We propose that hrHPV types with reduced immortalization capacity in vitro, reflected by a crisis period, require more genetic host cell aberrations to facilitate immortalization than types that can immortalize without crisis. This may in part explain the observed differences in HPV-type prevalence in cervical cancers and emphasizes that changes in the host cell genome contribute to HPV-induced carcinogenesis. PMID- 26993773 TI - Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor. AB - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are rare, highly malignant, and poorly understood sarcomas. The often poor outcome of MPNST highlights the necessity of identifying prognostic predictors for this aggressive sarcoma. Here, we investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs. RESULTS: aCGH and bioinformatics analysis identified frequent amplification of the FGFR1 gene. FISH analysis revealed that 26.9% MPNST samples had amplification of FGFR1, with both focal and polysomy patterns observed. IHC identified that FGFR1 protein expression was positively correlated with FGFR1 gene amplification. High expression of FGFR1 protein was associated with better overall survival (OS) and was an independent prognostic predictor for OS of MPNST patients. Additionally, combined expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better OS. FGFR4 protein was expressed 82.3% of MPNST samples, and was associated with poor disease-free survival. MATERIALS AND METHODS: We performed microarray-based comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Medical University Cancer Institute and Hospital. Fluorescence in situ hybridization (FISH) was used to validate the gene amplification detected by aCGH analysis. Another cohort of 63 formalin-fixed paraffin-embedded MPNST samples (including 52 samples for FISH assay) was obtained to explore FGFR1, 2, 3, and 4 protein expression by immunohistochemical (IHC) analysis. CONCLUSIONS: Our integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST. PMID- 26993774 TI - The NEDD8-activating enzyme inhibitor MLN4924 induces G2 arrest and apoptosis in T-cell acute lymphoblastic leukemia. AB - The first-in-class compound MLN4924 is a small molecule inhibitor that selectively inactivates NEDD8-activating enzyme (NAE). The anticancer effects of MLN4924 have been attributed to impaired neddylation of Cullin proteins. Here, we show that treatment of T-cell acute lymphoblastic leukemia (T-ALL) cells with MLN4924 potently suppressed the neddylation of Cullins and the oncogenic growth of T-ALL cells in-vitro. Moreover, MLN4924 induced disease regression in an in vivo xenograft model. MLN4924 also induced cell cycle arrest at G2 phase and apoptosis in T-ALL cells. However, inhibition of the neddylation of Cullins alone could not explain the effects of MLN4924 in T-ALL cells. Gene expression profiling indicated ribosome function, steroid biosynthesis, and hematopoietic cell lineage pathways were affected by MLN4924 treatment. MLN4924 also induced nucleolar disruption, suggesting nucleolar stress signaling might contribute to the anticancer effects of MLN4924 in T-ALL cells. In addition, MLN4924 treatment reduced 14-3-3xi?delta protein levels in T-ALL cells. Thus, MLN4924 may inhibit T ALL cell proliferation via several pathways. PMID- 26993775 TI - PIM1 destabilization activates a p53-dependent response to ribosomal stress in cancer cells. AB - Defects in ribosome biogenesis triggers a stress response (ribosomal stress) that can lead to growth arrest and apoptosis. Signaling pathways activated by ribosomal stress are specifically involved in the pathological mechanism of a group of disorders defined as ribosomopathies. However, more generally, the quality control of ribosome synthesis is part of the regulatory circuits that control cell metabolism. A number of studies identified tumor suppressor p53 as a central player in ribosomal stress. We have previously reported that the kinase PIM1 plays a role as a sensor for ribosome deficiency. In this report we address the relationship between PIM1 and p53 in cancer cell lines after depletion of a ribosomal protein. We identified a novel signaling pathway that includes the kinase AKT and the ubiquitin ligase MDM2. In fact, our results indicate that the lower level of PIM1, induced by ribosomal stress, causes inactivation of AKT, inhibition of MDM2 and a consequent p53 stabilization. Therefore, we propose that activation of p53 in response to ribosomal stress, is dependent on the pathway PIM1-AKT-MDM2. In addition, we report evidence that PIM1 level may be relevant to assess the sensitivity of cancer cells to chemotherapeutic drugs that induce ribosomal stress. PMID- 26993777 TI - AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition. AB - Histone deacetylases (HDACs) play critical roles in apoptosis and contribute to the proliferation of cancer cells. AR-42 is a novel Class I and II HDAC inhibitor that shows cytotoxicity against various human cancer cell lines. The present study aims to identify the target of AR-42 in hepatocellular carcinoma (HCC) as well as evaluate its therapeutic efficacy. We found that HDAC5 was upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. CCK8 and colony-formation assays showed that HDAC5 overexpression promotes proliferation in HCC cell lines. Treatment with AR-42 decreased HCC cell growth and increased caspase-dependent apoptosis, and this was rescued by HDAC5 overexpression. We demonstrated that AR-42 can inhibit the deacetylation activity of HDAC5 and its downstream targets in vitro and in vivo. Taken together, these results demonstrate for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy. PMID- 26993776 TI - Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future. AB - Although brain tumors have been known tremendously over the past decade, there are still many problems to be solved. The etiology of brain tumors is not well understood and the treatment remains modest. There is in great need to develop a suitable brain tumor models that faithfully mirror the etiology of human brain neoplasm and subsequently get more efficient therapeutic approaches for these disorders. In this review, we described the current status of animal models of brain tumors and analyzed their advantages and disadvantages. Additionally, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a versatile genome editing technology for investigating the functions of target genes, and its application were also introduced in our present work. We firstly proposed that brain tumor modeling could be well established via CRISPR/Cas9 techniques. And CRISPR/Cas9 mediated brain tumor modeling was likely to be more suitable for figuring out the pathogenesis of brain tumors, as CRISPR/Cas9 platform was a simple and more efficient biological toolbox for implementing mutagenesis of oncogenes or tumor suppressors that were closely linked with brain tumors. PMID- 26993778 TI - Driver or passenger effects of augmented c-Myc and Cdc20 in gliomagenesis. AB - PURPOSE: Cdc20 and c-Myc are commonly overexpressed in a broad spectrum of cancers, including glioblastoma (GBM). Despite this clear association, whether c Myc and Cdc20 overexpression is a driver or passenger event in gliomagenesis remains unclear. RESULTS: Both c-Myc and Cdc20 induced the proliferation of primary glial progenitor cells. c-Myc also promoted the formation of soft agar anchorage-independent colonies. In the RCAS/Ntv-a glia-specific transgenic mouse model, c-Myc increased the GBM incidence from 19.1% to 47.4% by 12 weeks of age when combined with kRas and Akt3 in Ntv-a INK4a-ARF (also known as CDKN2A)-null mice. In contrast, Cdc20 decreased the GBM incidence from 19.1% to 9.1%. Moreover, cell differentiation was modulated by c-Myc in kRas/Akt3-induced GBM on the basis of Nestin/GFAP expression (glial progenitor cell differentiation), while Cdc20 had no effect on primary glial progenitor cell differentiation. MATERIALS AND METHODS: We used glial progenitor cells from Ntv-a newborn mice to evaluate the role of c-Myc and Cdc20 in the proliferation and transformation of GBM in vitro and in vivo. We further determined whether c-Myc and Cdc20 have a driver or passenger role in GBM development using kRas/Akt3 signals in a RCAS/Ntv a mouse model. CONCLUSIONS: These results suggest that the driver or passenger of oncogene signaling is dependent on cellular status. c-Myc is a driver when combined with kRas/Akt3 oncogenic signals in gliomagenesis, whereas Cdc20 overexpression is a passenger. Inhibition of cell differentiation of c-Myc may be a target for anti-glioma therapy. PMID- 26993779 TI - Systematic evaluation of cancer risk associated with rs2292832 in miR-149 and rs895819 in miR-27a: a comprehensive and updated meta-analysis. AB - The aim of this study is to provide a precise quantification for the association between miR-149 T > C (rs2292832) and miR-27a A > G (rs895819) and the risk of cancer. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to assess the strengths of the associations. We identified 40 studies for pooled analyses. Overall, the results demonstrated that the rs2292832 polymorphism was subtly decrease the risk of breast cancer (CT + CC vs TT: OR = 0.83, 95% CI: 0.70-0.98, P = 0.03; CC vs CT + TT: OR = 0.80, 95% CI: 0.68-0.93, P = 0.00), and the rs895819 polymorphism wasassociated with significantly increased cancer risk in the Asian population (AG + GG vs AA: OR = 1.24, 95% CI: 1.03-1.50, P = 0.02) and in colorectal cancer subgroup (GG vs AA: OR = 1.45, 95% CI: 1.10-1.92, P = 0.00; AG + GG vs AA: OR = 1.35, 95% CI: 1.15-1.58, P = 0.00; GG vs AG + AA: OR = 1.36, 95% CI: 1.04-1.77, P = 0.02). In addition, a subtly decreased risk was observed in the Caucasian population and in breast cancer subgroup. In conclusion, the rs2292832 polymorphism was significantly associated with increased breast cancer risk, and the rs895819 polymorphism contributes to the susceptibility of colorectal and breast cancer. PMID- 26993781 TI - Direct and sensitive determination of glyphosate and aminomethylphosphonic acid in environmental water samples by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. AB - A novel method based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was developed for the sensitive determination of glyphosate and its major degradation product, AMPA in environmental water samples. The method involves the use of MS compatible mobile phases (0.1% formic acid in water and acetonitrile) for HPLC and direct analysis of water samples without sample derivatization. The method has been validated in different types of water matrices (drinking, surface and groundwater) by accuracy and precision studies with samples spiked at 0.1, 7.5 and 90 ppb. All mean accuracy values ranged from 85% to 112% for glyphosate and AMPA using both primary and secondary quantitative ion transitions (RSD <= 10%). Moreover, both primary and secondary ion transitions for glyphosate and AMPA can achieve the quantitation limits at 0.1 ppb. The linear dynamic range of the calibration curves were from 0.1 to 100 ppb for each analyte at each ion transitions with correlation coefficient higher than 0.997. PMID- 26993780 TI - Kruppel-like factor 8 activates the transcription of C-X-C cytokine receptor type 4 to promote breast cancer cell invasion, transendothelial migration and metastasis. AB - Kruppel-like factor 8 (KLF8) has been strongly implicated in breast cancer metastasis. However, the underlying mechanisms remain largely unknown. Here we report a novel signaling from KLF8 to C-X-C cytokine receptor type 4 (CXCR4) in breast cancer. Overexpression of KLF8 in MCF-10A cells induced CXCR4 expression at both mRNA and protein levels, as determined by quantitative real-time PCR and immunoblotting. This induction was well correlated with increased Boyden chamber migration, matrigel invasion and transendothelial migration (TEM) of the cells towards the ligand CXCL12. On the other hand, knockdown of KLF8 in MDA-MB-231 cells reduced CXCR4 expression associated with decreased cell migration, invasion and TEM towards CXCL12. Histological and database mining analyses of independent cohorts of patient tissue microarrays revealed a correlation of aberrant co elevation of KLF8 and CXCR4 with metastatic potential. Promoter analysis indicated that KLF8 directly binds and activates the human CXCR4 gene promoter. Interestingly, a CXCR4-dependent activation of focal adhesion kinase (FAK), a known upregulator of KLF8, was highly induced by CXCL12 treatment in KLF8 overexpressing, but not KLF8 deficient cells. This activation of FAK in turn induced a further increase in KLF8 expression. Xenograft studies showed that overexpression of CXCR4, but not a dominant-negative mutant of it, in the MDA-MB 231 cells prevented the invasive growth of primary tumor and lung metastasis from inhibition by knockdown of KLF8. These results collectively suggest a critical role for a previously unidentified feed-forward signaling wheel made of KLF8, CXCR4 and FAK in promoting breast cancer metastasis and shed new light on potentially more effective anti-cancer strategies. PMID- 26993782 TI - Water-compatible graphene oxide/molecularly imprinted polymer coated stir bar sorptive extraction of propranolol from urine samples followed by high performance liquid chromatography-ultraviolet detection. AB - Due to the high selectivity and stability, molecularly imprinted polymers (MIPs) have been successfully applied in stir bar sorptive extraction (SBSE) as a special coating to improve the selective extraction capability for target analytes. However, traditional MIPs usually suffer from incompatibility in aqueous media and low adsorption capacity, which limit the application of MIP coated stir bar in aqueous samples. To solve these problems, a water-compatible graphene oxides (GO)/MIP composite coated stir bar was prepared in this work by in situ polymerization. The prepared water-compatible GO/MIP coated stir bar presented good mechanical strength and chemical stability, and its recognition ability in aqueous samples was improved due to the polymerization of MIP in water environment, the adsorption capacity for target analytes was also increased by the addition of GO in MIP pre-polymer solution. Based on it, a method of water compatible GO/MIP coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detector (HPLV-UV) was proposed for the analysis of propranolol (PRO) in aqueous solution. The influencing factors of SBSE, such as sample pH, salt effect, stirring rate, extraction time, desorption solvent and desorption time, were optimized, and the analytical performance of the developed SBSE-HPLC-UV method was evaluated under the optimized conditions. The limit of detection (LOD) of the proposed method for PRO was about 0.37 MUg L( 1), and the enrichment factor (EF) was 59.7-fold (theoretical EF was 100-fold). The reproducibility was also investigated at concentrations of 5 MUg L(-1) and the relative standard deviation (RSD) was found to be 7.3% (n=7). The proposed method of GO/MIP coating-SBSE-HPLC-UV was successfully applied for the assay of the interested PRO drug in urine samples, and further extended to the investigation of the excretion of the drugs by monitoring the variation of the concentration of PRO in urine within 10h after drug-taking. PMID- 26993783 TI - Synthesis, liquid chromatographic fractionation and partial characterization of polybrominated dibenzofuran congeners. AB - Polybrominated dibenzofurans (PBDFs) are a class of highly toxic environmental contaminants which comprises 135 structurally different congeners. While the gas chromatographic separation and analysis of the most polychlorinated dibenzofurans (PCDFs) are well-documented, comparably little data is currently available in the case of PBDFs. In this study dibenzofuran was brominated to give a mixture of ~40 PBDFs with one to seven bromine atoms. This synthesis mixture was fractionated by both countercurrent chromatography (CCC) with the solvent system n hexane/toluene/acetonitrile and non-aqueous reversed-phase high performance liquid chromatography (RP-HPLC) with acetonitrile as the mobile phase. All together 80 consecutive CCC fractions and 40 HPLC fractions were taken and analyzed for PBDFs by gas chromatography coupled to mass spectrometry (GC/MS). CCC and RP-HPLC offered orthogonal separation of the PBDF mixture. As a consequence, selected CCC fractions were further fractionated by RP-HPLC. In this way, eight PBDFs could be isolated and the structures of twelve PBDFs were elucidated by proton magnetic resonance spectroscopy ((1)H NMR). PMID- 26993784 TI - Histological Classification and Immunohistochemical Evaluation of MDM2 and CDK4 Expression in Canine Liposarcoma. AB - Canine liposarcoma is an uncommon soft tissue sarcoma usually arising in the subcutis. While liposarcoma classification in dogs is based solely on histology, in humans it depends on the detection of genetic abnormalities that can lead to specific protein overexpression. This study is an immunohistochemical evaluation of MDM2 and CDK4 expression in canine liposarcoma designed to assess the correlation of these proteins with histologic type, grade, mitotic index and Ki67 labeling index and evaluate their utility in improving tumor classification. Fifty-three liposarcomas were retrospectively collected: 24 were well differentiated liposarcomas (WDL), 16 of which expressed MDM2 and 21 CDK4; 7 were myxoid liposarcomas (ML), 1 of which expressed MDM2 and 5 expressed CDK4; 18 were pleomorphic liposarcomas (PL), all were MDM2 negative and 12 expressed CDK4. Four tumors were morphologically consistent with dedifferentiated liposarcoma (DDL) a subtype described only in humans: 3 expressed MDM2 and 4 expressed CDK4. MDM2 expression correlated with histotype (highly expressed in WDL and DDL) and grade (highly expressed in grade 1 tumors). Histotype correlated with the Ki67 labeling index (lowest in WDL and highest in DDL). A revised classification, considering MDM2 expression, allowed 8 WDL to be reclassified as PL and correlated significantly with mitotic and Ki67 labeling index (both significantly lower in WDL and progressively higher in ML and DDL). These results partially parallel data reported for human liposarcomas, suggesting that WDL and DDL are distinct neoplastic entities characterized by MDM2 expression, which may represent a useful diagnostic and potentially prognostic marker for canine liposarcoma. PMID- 26993786 TI - Effect of repetitive transcranial magnetic stimulation on mood in healthy subjects. AB - BACKGROUND: High frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear. OBJECTIVE: Our aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects. DESIGN: In a randomised double-blind study, 20 subjects received 10 daily sessions of active (10 Hz frequency) or sham rTMS. The TMS coil was positioned on the left DLPFC through neuronavigation. Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales (VASs), and the Ekman 60 faces test. RESULTS: The 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTMS group presented a significant improvement in their adaptation to daily life, which was assessed through VAS. CONCLUSION: This study did not show any deleterious effect on mood and emotion recognition of 10 sessions of rTMS applied on the DLPFC in healthy subjects. This study also suggested a positive effect of rTMS on quality of life. PMID- 26993785 TI - The application of tDCS in psychiatric disorders: a brain imaging view. AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive, non convulsive technique for modulating brain function. In contrast to other non invasive brain stimulation techniques, where costs, clinical applicability, and availability limit their large-scale use in clinical practices, the low-cost, portable, and easy-to-use tDCS devices may overcome these restrictions. OBJECTIVE: Despite numerous clinical applications in large numbers of patients suffering from psychiatric disorders, it is not quite clear how tDCS influences the mentally affected human brain. In order to decipher potential neural mechanisms of action of tDCS in patients with psychiatric conditions, we focused on the combination of tDCS with neuroimaging techniques. DESIGN: We propose a contemporary overview on the currently available neurophysiological and neuroimaging data where tDCS has been used as a research or treatment tool in patients with psychiatric disorders. RESULTS: Over a reasonably short period of time, tDCS has been broadly used as a research tool to examine neuronal processes in the healthy brain. tDCS has also commonly been applied as a treatment application in a variety of mental disorders, with to date no straightforward clinical outcome and not always accompanied by brain imaging techniques. CONCLUSION: tDCS, as do other neuromodulation devices, clearly affects the underlying neuronal processes. However, research on these mechanisms in psychiatric patients is rather limited. A better comprehension of how tDCS modulates brain function will help us to define optimal parameters of stimulation in each indication and may result in the detection of biomarkers in favor of clinical response. PMID- 26993788 TI - New therapeutic approaches in psychiatry: contribution of neuroscience. PMID- 26993787 TI - Neural correlates of cognitive improvements following cognitive remediation in schizophrenia: a systematic review of randomized trials. AB - BACKGROUND: Cognitive impairments are a core feature in schizophrenia and are linked to poor social functioning. Numerous studies have shown that cognitive remediation can enhance cognitive and functional abilities in patients with this pathology. The underlying mechanism of these behavioral improvements seems to be related to structural and functional changes in the brain. However, studies on neural correlates of such enhancement remain scarce. OBJECTIVES: We explored the neural correlates of cognitive enhancement following cognitive remediation interventions in schizophrenia and the differential effect between cognitive training and other therapeutic interventions or patients' usual care. METHOD: We searched MEDLINE, PsycInfo, and ScienceDirect databases for studies on cognitive remediation therapy in schizophrenia that used neuroimaging techniques and a randomized design. Search terms included randomized controlled trial, cognitive remediation, cognitive training, rehabilitation, magnetic resonance imaging, positron emission tomography, electroencephalography, magnetoencephalography, near infrared spectroscopy, and diffusion tensor imaging. We selected randomized controlled trials that proposed multiple sessions of cognitive training to adult patients with a schizophrenia spectrum disorder and assessed its efficacy with imaging techniques. RESULTS: In total, 15 reports involving 19 studies were included in the systematic review. They involved a total of 455 adult patients, 271 of whom received cognitive remediation. Cognitive remediation therapy seems to provide a neurobiological enhancing effect in schizophrenia. After therapy, increased activations are observed in various brain regions mainly in frontal - especially prefrontal - and also in occipital and anterior cingulate regions during working memory and executive tasks. Several studies provide evidence of an improved functional connectivity after cognitive training, suggesting a neuroplastic effect of therapy through mechanisms of functional reorganization. Neurocognitive and social-cognitive training may have a cumulative effect on neural networks involved in social cognition. The variety of proposed programs, imaging tasks, and techniques may explain the heterogeneity of observed neural improvements. Future studies would need to specify the effect of cognitive training depending on those variables. PMID- 26993789 TI - Performance of interferon-gamma release assays in the diagnosis of confirmed active tuberculosis in immunocompetent children: a new systematic review and meta analysis. AB - BACKGROUND: Tuberculosis (TB) is a global public health problem, causing morbidity and mortality in adults and children. The most reliable diagnostic tools currently available are the in vivo Tuberculin Skin Test (TST) and the ex vivo Interferon-gamma release assays (IGRAs). Several clinical, radiological, and bacteriological features make the detection of active (overt disease) TB in children difficult. Although recently developed immunological assays such as QuantiFERON-TB Gold In-Tube (QFT-IT) and T-SPOT(r).TB are commonly used to identify active TB in adults, different evidence is required for diagnosis in children. The purpose of this study was to reassess the sensitivity and specificity of IGRAs in detecting microbiologically confirmed active TB in immunocompetent children. METHODS: A systematic review and meta-analysis of studies reporting on the diagnostic accuracy of tests for TB in immunocompetent children aged 0-18 years, with confirmation by positive M. tuberculosis cultures, were undertaken. Electronic databases were searched up to September 2015 and study quality assessment was performed using QUADAS-2. RESULTS: Fifteen studies were included in our meta-analysis. Results showed that there were no significant differences in sensitivity between TST (88.2%, 95% confidence interval [CI] 79.4 94.2%), QFT-IT (89.6%, 95% CI 79.7-95.7%) and T SPOT (88.5%, 95% CI 80.4-94.1%). However, both QFT-IT (95.4%, 95% CI 93.8-96.6%) and T-SPOT (96.8%, 95% CI 94.2 98.5%) have significantly higher specificity than TST (86.3%, 95% CI 83.9-88.6%). CONCLUSIONS: QFT-IT and T-SPOT have higher specificity than TST for detecting active TB cases in immunocompetent children. PMID- 26993790 TI - Establishing an Anaesthesia and Intensive Care partnership and aiming for national impact in Tanzania. AB - Anaesthesia and Intensive Care is a neglected specialty in low-income countries. There is an acute shortage of health workers - several low-income countries have less than 1 anaesthesia provider per 100,000 population. Only 1.5% of hospitals in Africa have the intensive care resources needed for managing patients with sepsis. Health partnerships between institutions in high and low-income countries have been proposed as an effective way to strengthen health systems. The aim of this article is to describe the origin and conduct of a health partnership in Anaesthesia and Intensive Care between institutions in Tanzania and Sweden and how the partnership has expanded to have an impact at regional and national levels.The Muhimbili-Karolinska Anaesthesia and Intensive Care Collaboration was initiated in 2008 on the request of the Executive Director of Muhimbili National Hospital in Dar es Salaam. The partnership has conducted training courses, exchanges, research projects and introduced new equipment, routines and guidelines. The partnership has expanded to include all hospitals in Dar es Salaam. Through the newly formed Life Support Foundation, the partnership has had a national impact assisting the reanimation of the Society of Anaesthesiologists of Tanzania and has seen a marked increase of the number of young doctors choosing a residency in Anaesthesia and Intensive Care. PMID- 26993791 TI - RNAi-mediated gene knockdown by microinjection in the model entomopathogenic nematode Heterorhabditis bacteriophora. AB - BACKGROUND: Parasitic nematodes threaten the health of humans and livestock and cause a major financial and socioeconomic burden to modern society. Given the widespread distribution of diseases caused by parasitic nematodes there is an urgent need to develop tools that will elucidate the genetic complexity of host parasite interactions. Heterorhabditis bacteriophora is a parasitic nematode that allows simultaneous monitoring of nematode infection processes and host immune function, and offers potential as a tractable model for parasitic nematode infections. However, molecular tools to investigate these processes are required prior to its widespread acceptance as a robust model organism. In this paper we describe microinjection in adult H. bacteriophora as a suitable means of dsRNA delivery to knockdown gene transcripts. METHODS: RNA interference was used to knockdown four genes by injecting dsRNA directly into the gonad of adult hermaphrodite nematodes. RNAi phenotypes were scored in the F1 progeny on the fifth day post-injection, and knockdown of gene-specific transcripts was quantified with real-time quantitative RT-PCR (qRT-PCR). RESULTS: RNAi injection in adult hermaphrodites significantly decreased the level of target transcripts to varying degrees when compared with controls. The genes targeted by RNAi via injection included cct-2, nol-5, dpy-7, and dpy-13. In each case, RNAi knockdown was confirmed phenotypically by examining the progeny of injected animals, and also confirmed at the transcriptional level by real-time qRT-PCR. CONCLUSIONS: Here we describe for the first time the successful use of microinjection to knockdown gene transcripts in H. bacteriophora. This technique can be used widely to study the molecular basis of parasitism. PMID- 26993792 TI - Insomnia: the Sleeping Giant of Pediatric Public Health. AB - Insomnia among children and adolescents is ubiquitous and takes a great toll on youth and their families, impacting academic achievement, mood, social functioning, and a variety of developmental outcomes. Unfortunately, however, pediatric insomnia most often remains unidentified and untreated. When treatment is provided, it is most often in the form of medications, which are not FDA approved for that indication in children and adolescents. A comprehensive literature review was employed to establish the recommendations in this report. This article provides a review of sleep physiology and both current and recommended approaches to assessing and treating pediatric insomnia. Comprehensive assessment, accurate diagnosis, and evidence-based treatment of insomnia is imperative to the healthy development of children and adolescents. While clinicians often prescribe a variety of medications to treat pediatric insomnia, there is insufficient data to demonstrate efficacy and endorse their routine use. At this time, behavioral techniques, such as cognitive behavior therapy for insomnia and sleep hygiene education, should remain the first line of treatment. As a second-line consideration, melatonin, a dietary supplement, may be effective. Pediatric insomnia has an enormous impact on children, adolescents, and their families that requires adequate attention from clinicians and parents alike. PMID- 26993793 TI - Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum. AB - BACKGROUND: Hyperglycemia and increased levels of methylglyoxal (MGO) can trigger the development of vascular complications in diabetes. Resveratrol and quercetin are red wine polyphenols with known beneficial cardiovascular properties, including an antioxidant capacity. This study evaluated whether resveratrol and/or quercetin could prevent in vitro-induced diabetic changes in neurogenic and vascular relaxant responses of mouse arteries and corpora cavernosa. METHODS: Isometric tension of isolated aorta, mesenteric arteries and corpora cavernosa was measured using organ bath systems. Diabetic conditions were mimicked in vitro by co-incubating the tissues for 2 h with high glucose (HG, 30 mM) and MGO (120 uM). RESULTS: The presence of HG and MGO significantly blunted acetylcholine (Ach)-induced relaxations in corpora cavernosa and mesenteric arteries but not in aorta. Electrical field stimulated (EFS) responses of corpora cavernosa were also significantly inhibited by these diabetic conditions. In corpora cavernosa 2 h co incubation with resveratrol (30 uM) or quercetin (30 uM) significantly attenuated HG and MGO-induced deficits in Ach- and EFS-responses. CONCLUSIONS: Our study demonstrates that in mouse arteries, HG and MGO rather affect endothelium derived hyperpolarizing factor-mediated than nitric oxide (NO)-mediated relaxations. In corpora cavernosa HG and MGO interfere with NO release. Resveratrol and quercetin protect mouse corpora cavernosa from diabetic-induced damage to NO-mediated relaxant responses. This might rely on their antioxidant capacity. PMID- 26993794 TI - Tactile stimulation effects on hippocampal neurogenesis and spatial learning and memory in prenatally stressed rats. AB - Neurogenesis in the dentate gyrus (DG) of the hippocampus is increased by spatial learning and postnatal stimulation. Conversely, prenatal stress (PS) produces a decrease in the proliferation of hippocampal granular cells. This work evaluated the effect of postnatal tactile stimulation (PTS), when applied from birth to adulthood, on cognitive performance and hippocampal neurogenesis (survival and differentiation) in PS female and male rats. The response of the adrenal axis to training in the Morris water maze (MWM) was also analyzed. PS was provided during gestational days 15 through 21. Hippocampal neurogenesis and cognitive performance in the MWM were assessed at an age of three months. Results showed that escape latencies of both female and male PS rats were longer compared to those of their controls (CON). DG cell survival increased in the PS female rats. Corticosterone concentrations were significantly higher in the male and female PS rats after MWM training. PTS improved escape latencies and increased the number of new neurons in the DG of PS animals, and their corticosterone concentrations were similar to those in CON. In CON, PTS diminished DG cell survival but increased differentiation and reduces latency in the MWM. These results show that long-term PTS in PS animals might prevent learning deficits in adults through increase in the number of DG new cells and decrease of the reactivity of the adrenal axis to MWM training. PMID- 26993795 TI - Adolescents and adults differ in the immediate and long-term impact of nicotine administration and withdrawal on cardiac norepinephrine. AB - Cardiovascular responses to smoking cessation may differ in adolescents compared to adults. We administered nicotine by osmotic minipump infusion for 17 days to adolescent and adult rats (30 and 90 days of age, respectively) and examined cardiac norepinephrine levels during treatment, after withdrawal, and for months after cessation. In adults, nicotine evoked a significant elevation of cardiac norepinephrine and a distinct spike upon withdrawal, after which the levels returned to normal; the effect was specific to males. In contrast, adolescents did not show significant changes during nicotine treatment or in the immediate post-withdrawal period. However, beginning in young adulthood, males exposed to adolescent nicotine showed sustained elevations of cardiac norepinephrine, followed by later-emerging deficits that persisted through six months of age. We then conducted adolescent exposure using twice-daily injections, a regimen that augments stress associated with inter-dose withdrawal episodes. With the injection route, adolescents showed an enhanced cardiac norepinephrine response, reinforcing the relationship between withdrawal stress and a surge in cardiac norepinephrine levels. The relative resistance of adolescents to the acute nicotine withdrawal response is likely to make episodic nicotine exposure less stressful or aversive than in adults. Equally important, the long-term changes after adolescent nicotine exposure resemble those known to be associated with risk of hypertension in young adulthood (elevated norepinephrine) or subsequent congestive heart disease (norepinephrine deficits). Our findings reinforce the unique responses and consequences of nicotine exposure in adolescence, the period in which most smokers commence tobacco use. PMID- 26993796 TI - Treatment adequacy of anxiety disorders among young adults in Finland. AB - BACKGROUND: Anxiety disorders are common in early adulthood, but general population studies concerning the treatment adequacy of anxiety disorders taking into account appropriate pharmacological and psychological treatment are scarce. The aims of this study were to examine treatments received for anxiety disorders in a Finnish general population sample of young adults, and to define factors associated with receiving minimally adequate treatment and with dropping out from treatment. METHODS: A questionnaire containing several mental health screens was sent to a nationally representative two-stage cluster sample of 1894 Finns aged 19 to 34 years. All screen positives and a random sample of screen negatives were invited to a mental health assessment including a SCID interview. For the final diagnostic assessment, case records from mental health treatments for the same sample were obtained. This article investigates treatment received, treatment adequacy and dropouts from treatment of 79 participants with a lifetime anxiety disorder (excluding those with a single specific phobia). Based on all available information, receiving antidepressant or buspirone medication for at least 2 months with at least four visits with any type of physician or at least eight sessions of psychotherapy within 12 months or at least 4 days of hospitalization were regarded as minimally adequate treatment for anxiety disorders. Treatment dropout was rated if the patient discontinued the visits by his own decision despite having an adequate treatment strategy according to the case records. RESULTS: Of participants with anxiety disorders (excluding those with a single specific phobia), 41.8 % had received minimally adequate treatment. In the multivariate analysis, comorbid substance use disorder was associated with antidepressant or buspirone medication lasting at least 2 months. Those who were currently married or cohabiting had lower odds of having at least four visits with a physician a year. None of these factors were associated with the final outcome of minimally adequate treatment or treatment dropout. Participants with comorbid personality disorders received and misused benzodiazepines more often than others. CONCLUSIONS: More efforts are needed to provide adequate treatment for young adults with anxiety disorders. Attention should be paid to benzodiazepine prescribing to individuals with personality disorders. PMID- 26993797 TI - Mother-Child Discrepancy in Perceived Family Functioning and Adolescent Developmental Outcomes in Families Experiencing Economic Disadvantage in Hong Kong. AB - Though growing attention has been devoted to examining informant discrepancies of family attributes in social science research, studies that examine how interactions between mother-reported and adolescent-reported family functioning predict adolescent developmental outcomes in underprivileged families are severely lacking. The current study investigated the difference between mothers and adolescents in their reports of family functioning, as well as the relationships between mother-reported and adolescent-reported family functioning and adolescent developmental outcomes in a sample of 432 Chinese single-mother families (mean age of adolescents = 13.7 years, 51.2 % girls, mean age of mothers = 43.5 years, 69.9 % divorced) experiencing economic disadvantage in Hong Kong. Polynomial regression analyses were conducted to assess whether discrepancy in family functioning between mother reports and adolescent reports predicted resilience, beliefs in the future, cognitive competence, self-efficacy and self determination of adolescents. The results indicated that adolescents reported family functioning more negatively than did their mothers. Polynomial regression analyses showed that the interaction term between mothers' reports and adolescents' reports of family functioning predicted adolescent developmental outcomes in Chinese single-mother families living in poverty. Basically, under poor adolescent-reported family functioning, adolescent development would be relatively better if their mothers reported more positive family functioning. In contrast, under good adolescent-reported family functioning, adolescents expressed better developmental outcomes when mothers reported lower levels of family functioning than those mothers who reported higher levels of family functioning. The findings provide insights on how congruency and discrepancy between informant reports of family functioning would influence adolescent development. Theoretical and practical implications of the findings are discussed. PMID- 26993798 TI - Youth services: the need to integrate mental health, physical health and social care: Commentary on Malla et al.: From early intervention in psychosis to youth mental health reform: a review of the evolution and transformation of mental health services for young people. AB - Mental distress and mental health disorders are common in young people. Indeed, over 75 % of mental disorders begin before the age of 25 years. Long delays in seeking help for illnesses are common, initial intervention is often ineffective and young people are at risk of disengaging with treatment, particularly when they are expected to move from child and adolescent treating teams to adult services. All of these factors mean that young people are vulnerable to prolonged mental ill-health and its consequences, including educational failure, unemployment, social disengagement and deprivation, and development of further mental health problems including substance misuse. Malla et al. present different service models that attempt to address these issues. Additionally, there needs to be a focus on physical health and social care as these are intertwined with mental health. PMID- 26993799 TI - Analysis of the Uncertainty in Microbubble Characterization. AB - There is increasing interest in the use of microbubble contrast agents for quantitative imaging applications such as perfusion and blood pressure measurement. The response of a microbubble to ultrasound excitation is, however, extremely sensitive to its size, the properties of its coating and the characteristics of the sound field and surrounding environment. Hence the results of microbubble characterization experiments can be significantly affected by experimental uncertainties, and this can limit their utility in predictive modelling. The aim of this study was to attempt to quantify these uncertainties and their influence upon measured microbubble characteristics. Estimates for the parameters characterizing the microbubble coating were obtained by fitting model data to numerical simulations of microbubble dynamics. The effect of uncertainty in different experimental parameters was gauged by modifying the relevant input values to the fitting process. The results indicate that even the minimum expected uncertainty in, for example, measurements of microbubble radius using conventional optical microscopy, leads to variations in the estimated coating parameters of ~20%. This should be taken into account in designing microbubble characterization experiments and in the use of data obtained from them. PMID- 26993801 TI - Social Representations of Older Adults Among Chilean Elders of Three Cities with Different Historical and Sociodemographic Background. AB - The study was aimed to explore social representations of older adults among Chilean people aged 70 or more, living in three cities with differences in historical, geographic, and sociodemographic characteristics and to explore the importance of the local context on their shaping. Multiple correspondence analysis was employed to analyze the terms produced through free-word association technique, by 741 people. The two first dimensions explained 62.4 % of the inertia and showed that the contribution of city of residence was several times higher than the average; the contribution of gender and educational level was higher than average as well. The northern city representations were characterized by positive terms, whereas more negative contents were characteristic of the city of the center, and terms without an explicitly positive or negative assessment were associated to the southern city. These findings reinforce the relevance of the local sociocultural context in shaping social representations of old age and stress the importance of considering particular regional features in the design of policies and interventions aimed to recognize and integrate older adults in Chile. PMID- 26993800 TI - Neuregulin-1 controls an endogenous repair mechanism after spinal cord injury. AB - Following traumatic spinal cord injury, acute demyelination of spinal axons is followed by a period of spontaneous remyelination. However, this endogenous repair response is suboptimal and may account for the persistently compromised function of surviving axons. Spontaneous remyelination is largely mediated by Schwann cells, where demyelinated central axons, particularly in the dorsal columns, become associated with peripheral myelin. The molecular control, functional role and origin of these central remyelinating Schwann cells is currently unknown. The growth factor neuregulin-1 (Nrg1, encoded by NRG1) is a key signalling factor controlling myelination in the peripheral nervous system, via signalling through ErbB tyrosine kinase receptors. Here we examined whether Nrg1 is required for Schwann cell-mediated remyelination of central dorsal column axons and whether Nrg1 ablation influences the degree of spontaneous remyelination and functional recovery following spinal cord injury. In contused adult mice with conditional ablation of Nrg1, we found an absence of Schwann cells within the spinal cord and profound demyelination of dorsal column axons. There was no compensatory increase in oligodendrocyte remyelination. Removal of peripheral input to the spinal cord and proliferation studies demonstrated that the majority of remyelinating Schwann cells originated within the injured spinal cord. We also examined the role of specific Nrg1 isoforms, using mutant mice in which only the immunoglobulin-containing isoforms of Nrg1 (types I and II) were conditionally ablated, leaving the type III Nrg1 intact. We found that the immunoglobulin Nrg1 isoforms were dispensable for Schwann cell-mediated remyelination of central axons after spinal cord injury. When functional effects were examined, both global Nrg1 and immunoglobulin-specific Nrg1 mutants demonstrated reduced spontaneous locomotor recovery compared to injured controls, although global Nrg1 mutants were more impaired in tests requiring co-ordination, balance and proprioception. Furthermore, electrophysiological assessments revealed severely impaired axonal conduction in the dorsal columns of global Nrg1 mutants (where Schwann cell-mediated remyelination is prevented), but not immunoglobulin-specific mutants (where Schwann cell-mediated remyelination remains intact), providing robust evidence that the profound demyelinating phenotype observed in the dorsal columns of Nrg1 mutant mice is related to conduction failure. Our data provide novel mechanistic insight into endogenous regenerative processes after spinal cord injury, demonstrating that Nrg1 signalling regulates central axon remyelination and functional repair and drives the trans-differentiation of central precursor cells into peripheral nervous system-like Schwann cells that remyelinate spinal axons after injury. Manipulation of the Nrg1 system could therefore be exploited to enhance spontaneous repair after spinal cord injury and other central nervous system disorders with a demyelinating pathology.media 1vid110.1093/brain/aww039_video_abstractaww039_video_abstract. PMID- 26993803 TI - Vegfr3-CreER (T2) mouse, a new genetic tool for targeting the lymphatic system. AB - The lymphatic system is essential in many physiological and pathological processes. Still, much remains to be known about the molecular mechanisms that control its development and function and how to modulate them therapeutically. The study of these mechanisms will benefit from better controlled genetic mouse models targeting specifically lymphatic endothelial cells. Among the genes expressed predominantly in lymphatic endothelium, Vegfr3 was the first one identified and is still considered to be one of the best lymphatic markers and a key regulator of the lymphatic system. Here, we report the generation of a Vegfr3 CreER (T2) knockin mouse by gene targeting in embryonic stem cells. This mouse expresses the tamoxifen-inducible CreER(T2) recombinase under the endogenous transcriptional control of the Vegfr3 gene without altering its physiological expression or regulation. The Vegfr3-CreER (T2) allele drives efficient recombination of floxed sequences upon tamoxifen administration specifically in Vegfr3-expressing cells, both in vitro, in primary lymphatic endothelial cells, and in vivo, at different stages of mouse embryonic development and postnatal life. Thus, our Vegfr3-CreER (T2) mouse constitutes a new powerful genetic tool for lineage tracing analysis and for conditional gene manipulation in the lymphatic endothelium that will contribute to improve our current understanding of this system. PMID- 26993802 TI - Experimental Evaluation of Proposed Small-Molecule Inhibitors of Water Channel Aquaporin-1. AB - The aquaporin-1 (AQP1) water channel is a potentially important drug target, as AQP1 inhibition is predicted to have therapeutic action in edema, tumor growth, glaucoma, and other conditions. Here, we measured the AQP1 inhibition efficacy of 12 putative small-molecule AQP1 inhibitors reported in six recent studies, and one AQP1 activator. Osmotic water permeability was measured by stopped-flow light scattering in human and rat erythrocytes that natively express AQP1, in hemoglobin-free membrane vesicles from rat and human erythrocytes, and in plasma membrane vesicles isolated from AQP1-transfected Chinese hamster ovary cell cultures. As a positive control, 0.3 mM HgCl2 inhibited AQP1 water permeability by >95%. We found that none of the tested compounds at 50 uM significantly inhibited or increased AQP1 water permeability in these assays. Identification of AQP1 inhibitors remains an important priority. PMID- 26993804 TI - Factors associated with perpetration of intimate partner violence among college students in China. AB - OBJECTIVES: Intimate partner violence (IPV) is a significant public health threat that contributes to a wide range of physical and mental health issues for victims. However, critical information on IPV in China is still lacking. The purpose of this study was to examine factors affecting IPV perpetration as well as victimisation in mainland China. METHODS: The data were from the International Dating Violence Study 2001-2006 (N=731). The lifetime prevalence of victimisation and perpetration of IPV (ie, physical, psychological and/or sexual) was used for analysis. The following individual characteristics and exposures were included in the analysis based on previous studies which showed an association between these characteristics and IPV: childhood sexual abuse history, substance abuse, violence socialisation, dominance, anger management and communication problems. RESULTS: Perpetrators of physical IPV have a higher prevalence of being victims of IPV than non-perpetrators. Female perpetrators have a higher prevalence of anger management issues than male perpetrators. Levels of anger management and violence socialisation are predictors of physical IPV perpetration only for female perpetrators. CONCLUSIONS: IPV interventions for victims should include interventions for perpetration given that many Chinese victims of IPV also perpetrate IPV. Practice and research on professional education and services for treating individuals who have IPV experience need to be developed in China. PMID- 26993805 TI - Nanoscopic insights into seeding mechanisms and toxicity of alpha-synuclein species in neurons. AB - New strategies for visualizing self-assembly processes at the nanoscale give deep insights into the molecular origins of disease. An example is the self-assembly of misfolded proteins into amyloid fibrils, which is related to a range of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. Here, we probe the links between the mechanism of alpha-synuclein (AS) aggregation and its associated toxicity by using optical nanoscopy directly in a neuronal cell culture model of Parkinson's disease. Using superresolution microscopy, we show that protein fibrils are taken up by neuronal cells and act as prion-like seeds for elongation reactions that both consume endogenous AS and suppress its de novo aggregation. When AS is internalized in its monomeric form, however, it nucleates and triggers the aggregation of endogenous AS, leading to apoptosis, although there are no detectable cross-reactions between externally added and endogenous protein species. Monomer-induced apoptosis can be reduced by pretreatment with seed fibrils, suggesting that partial consumption of the externally added or excess soluble AS can be significantly neuroprotective. PMID- 26993806 TI - Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2. AB - The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity. PMID- 26993807 TI - Spatial Stream Segregation by Cats. AB - Listeners can perceive interleaved sequences of sounds from two or more sources as segregated streams. In humans, physical separation of sound sources is a major factor enabling such stream segregation. Here, we examine spatial stream segregation with a psychophysical measure in domestic cats. Cats depressed a pedal to initiate a target sequence of brief sound bursts in a particular rhythm and then released the pedal when the rhythm changed. The target bursts were interleaved with a competing sequence of bursts that could differ in source location but otherwise were identical to the target bursts. This task was possible only when the sources were heard as segregated streams. When the sound bursts had broad spectra, cats could detect the rhythm change when target and competing sources were separated by as little as 9.4 degrees . Essentially equal levels of performance were observed when frequencies were restricted to a high, 4 to-25-kHz, band in which the principal spatial cues presumably were related to sound levels. When the stimulus band was restricted from 0.4 to 1.6 kHz, leaving interaural time differences as the principal spatial cue, performance was severely degraded. The frequency sensitivity of cats in this task contrasts with that of humans, who show better spatial stream segregation with low- than with high-frequency sounds. Possible explanations for the species difference includes the smaller interaural delays available to cats due to smaller sizes of their heads and the potentially greater sound-level cues available due to the cat's frontally directed pinnae and higher audible frequency range. PMID- 26993808 TI - Microsporidia Alfvenia sibirica sp. n. and Agglomerata cladocera (Pfeiffer) 1895, from Siberian microcrustaceans and phylogenetic relationships within the "Aquatic outgroup" lineage of fresh water microsporidia. AB - Here we report on two microsporidia from freshwater crustaceans collected during the ongoing survey for microsporidia in the river Karasuk and adjacent waterbodies (Novosibirsk region, Western Siberia). The first species parasitized hypoderm and fat body of a cyclopid Cyclops sp. (Maxillopoda, Copedoda) and produced oval spores, measured 2.0*3.6MUm (fixed) enclosed individually or in small groups in fragile sporophorous vesicles (SVs). We describe it here as Alfvenia sibirica sp. n. The second species infected the same tissues of a cladoceran Daphnia magna (Branchiopoda, Phyllopoda). Its spores were pyriform, 2.3*4.0MUm (fixed), and resided in relatively persistent SVs in groups of 8-16. This species was identified as a Siberian isolate (Si) of Agglomerata cladocera (Pfeifer) because ultrastructurally it was hardly distinguishable from A. cladocera recorded from England from the same host (Larsson et al., 1996). A. cladocera (Si) shared 99% SSU rDNA sequence similarity to Binucleata daphniae from D. magna collected in Belgium (Refardt et al., 2008). The major outcome of our work is that we present molecular (SSUrDNA) characterization coupled with EM description, for representatives of two genera, Alfvenia (encompasses 3 described so far species) and Agglomerata (7 species), which allowed us to place these two genera on the phylogenetic tree. We also summarized the literature data on Alfvenia and Agglomerata spp., and provided their comparative morphological analysis. These two genera belong to so called "Aquatic outgroup" (Vossbrinck et al., 2004), a poorly resolved lineage, a sister to Amblyosporidae. This lineage probably includes majority of fresh water forms of microsporidia, most of which remain undescribed. SSUrDNA-based phylogenetic analysis and analysis of hosts suggest that diversification within the "Aquatic outgroup" could have been connected with the host switch from dipterans or copepods to cladocerans that had occurred in some ancestral Amblyospora-related lineage(s). PMID- 26993809 TI - Primary benign myopericytoma of the left atrium. PMID- 26993811 TI - MRI and (1)H-MRS in adenosine kinase deficiency. AB - INTRODUCTION: Adenosine kinase deficiency (ADK deficiency) is a recently described disorder of methionine and adenosine metabolism resulting in a neurological phenotype with developmental delay, muscular hypotonia, and epilepsy as well as variable systemic manifestations. The underlying neuropathology is poorly understood. We have investigated MRI and (1)H-MRS changes in ADK deficiency in order to better understand the in vivo neuropathologic changes of ADK deficiency. METHODS: Systematic evaluation of 21 MRIs from eight patients (age range 9 days-14.6 years, mean 3.9 years, median 2.7 years) including diffusion-weighted imaging in six and (1)H-MRS in five patients. RESULTS: Brain maturation was delayed in the neonatal period and in infancy (6/6), but ultimately complete. White matter changes occurring in five of eight patients were discrete, periventricular, and unspecific (4/5), or diffuse with sparing of optic radiation, corona radiata, and pyramidal tracts (1/5). Choline was low in white matter spectra (3/3), while there was no indication of low creatine in white matter or basal ganglia (5/5), and diffusion was variably decreased or increased. Central tegmental tract hyperintensity was a common finding (6/8), as was supratentorial atrophy (6/8). CONCLUSIONS: MRI changes in ADK deficiency consist of delayed but ultimately completed brain maturation with later onset of mostly unspecific white matter changes and potentially transient central tegmental tract hyperintensity. Immaturity on neonatal MRI is consistent with prenatal onset of disease and reduced choline with lower membrane turnover resulting in delayed myelination and deficient myelin maintenance. PMID- 26993814 TI - Oxidative stress and cardiac dysfunction in children with chronic renal failure on regular hemodialysis. AB - OBJECTIVE: The objective of this study was to evaluate cardiac function in children with end-stage renal disease (ESRD) on regular hemodialysis using speckle tracking echocardiography (STE) and correlate results with plasma glutathione level as a marker of oxidative stress. METHODS: The study involved 30 children with ESRD and 30 healthy controls. The plasma glutathione and C-reactive protein (CRP) levels were measured, and cardiac function was evaluated using conventional echocardiography and STE. RESULTS: Plasma glutathione levels were significantly lower and CRP significantly higher in patients than in controls. Children with ESRD had significant systolic and diastolic cardiac dysfunctions detected by STE compared with controls. Conventional echocardiography failed to detect these dysfunctions. There was significant increase in left-ventricular relative wall thickness (LV-RWT) in patients, especially those with hypertension, compared with the control group. There was also significant impairment of LV and right-ventricular (RV) global longitudinal strain (GLS) and torsion; however, LV GLS was significantly better in hypertensive than in normotensive patients. The degree of impairment in GLS and cardiac torsion negatively correlated with plasma glutathione levels. CONCLUSION: Significant oxidative stress was present in children with ESRD and was correlated with the degree of cardiac dysfunction detected early using the new cardiac imaging modality, STE. PMID- 26993815 TI - Utility of fractional excretion of urea in the differential diagnosis of acute kidney injury in children. AB - INTRODUCTION: The fractional excretion of sodium (FENa) has been used as an index for the differential diagnosis of acute tubular necrosis (ATN) and prerenal acute kidney injury (AKI). The reliability of this index, however, decreases with the use of the diuretic agent furosemide. The fractional excretion of urea nitrogen (FEUN) has been shown to be useful in such settings in adults. The objective of this study was to examine whether FEUN is also useful in these settings in children. METHODS: We assessed 102 episodes of AKI in 74 children, classifying these into three groups based on history, physical examination, urine examination and subsequent clinical course: (1) prerenal AKI without furosemide (N = 37), (2) prerenal AKI with furosemide (N = 32) and (3) ATN (N = 33). RESULTS: Of the 37 prerenal AKI episodes without furosemide, 35 showed low FENa of <1 %, with an overall average of 0.35 +/- 0.11 %, whereas prerenal AKI with furosemide (1.63 +/ 0.37 %) and ATN (8.76 +/- 2.11 %) were associated with a higher FENa. FEUN in the clinical setting of prerenal AKI was lower than that in ATN (27.9 +/- 2.1 vs. 51.6 +/- 3.8 %, respectively) and, in contrast to FENa, not significantly different between the categories of prerenal AKI with and without furosemide (29.2 +/- 3.1 vs. 25.1 +/- 2.9, respectively). The sensitivity of FEUN <35 % was 75 % in prerenal AKI with furosemide, whereas that of FENa was 53 %. CONCLUSIONS: FEUN is useful in detecting prerenal AKI in children administered furosemide. PMID- 26993816 TI - Barriers to Innovation in Urban Wastewater Utilities: Attitudes of Managers in California. AB - In many regions of the world, urban water systems will need to transition into fundamentally different forms to address current stressors and meet impending challenges-faster innovation will need to be part of these transitions. To assess the innovation deficit in urban water organizations and to identify means for supporting innovation, we surveyed wastewater utility managers in California. Our results reveal insights about the attitudes towards innovation among decision makers, and how perceptions at the level of individual managers might create disincentives for experimentation. Although managers reported feeling relatively unhindered organizationally, they also spend less time on innovation than they feel they should. The most frequently reported barriers to innovation included cost and financing; risk and risk aversion; and regulatory compliance. Considering these results in the context of prior research on innovation systems, we conclude that collective action may be required to address underinvestment in innovation. PMID- 26993817 TI - The Role of County Surveyors and County Drainage Boards in Addressing Water Quality. AB - Water quality problems stemming from the Midwestern U.S. agricultural landscape have been widely recognized and documented. The Midwestern state of Indiana contains tens of thousands of miles of regulated drains that represent biotic communities that comprise the headwaters of the state's many rivers and creeks. Traditional management, however, reduces these waterways to their most basic function as conveyances, ignoring their role in the ecosystem as hosts for biotic and abiotic processes that actively regulate the fate and transport of nutrients and farm chemicals. Novel techniques and practices such as the two-stage ditch, denitrifying bioreactor, and constructed wetlands represent promising alternatives to traditional management approaches, yet many of these tools remain underutilized. To date, conservation efforts and research have focused on increasing the voluntary adoption of practices among agricultural producers. Comparatively little attention has been paid to the roles of the drainage professionals responsible for the management of waterways and regulated drains. To address this gap, we draw on survey responses from 39 county surveyors and 85 drainage board members operating in Indiana. By examining the backgrounds, attitudes, and actions of these individuals, we consider their role in advocating and implementing novel conservation practices. PMID- 26993818 TI - Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting. AB - OBJECTIVE: The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model. METHODS: Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188 folate-GGCE. RESULTS: The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro SPECT/CT in mice injected with Tc-99m- or Re-188-folate-GGCE. The tumor uptake of these molecules was completely suppressed when excess free folate was co administered. CONCLUSION: Isostructural Tc-99m- and Re-188-folate-GGCE showed high and FR-specific uptake by tumors and generally favorable tumor:normal organ ratios. The tumor targeting capabilities of Tc-99m- and Re-188-folate-GGCE were clearly evident on serial imaging studies. This isostructural pair may have potential diagnostic and theranostic applications for FR-positive tumors. PMID- 26993819 TI - Fully automated quality assurance and localization of volumetric MEG for single subject mapping. AB - BACKGROUND: Robust and reproducible source mapping with magnetoencephalography is particularly challenging at the individual level. We evaluated a receiver operating characteristic reliability (ROC-r) method for automated production of volumetric MEG maps in single-subjects. ROC-r provides quality assurance comparable to that offered by goodness-of-fit (GoF) and confidence volume (CV) for equivalent current dipole (ECD) modeling. NEW METHOD: ROC-r utilizes within session reproducibility for quality assurance, latency identification, and thresholding of volumetric source maps. We tested ROC-r on simulated and real MEG with a strongly focal source, using somatosensory evoked fields (SEFs) elicited by bilateral median nerve stimulation (MNS). For quality assurance, the ROC-r reliable fraction (FR) was compared to the ECD GoF and CV. Peak beamformer locations and latencies identified by ROC-r were compared to the ECD for co localization accuracy. RESULTS: The predominant component of the SEF response occurred around 35ms, contralateral to the MNS. COMPARISON WITH EXISTING METHODS: FR and 1/CV were more strongly correlated (mean Pearson's correlation: 0.76; 95% CI 0.60-0.87) than FR and GoF (0.65; 95% CI 0.32-0.85). There was no difference in the latency of the peak GoF (35.0+/-0.6ms), CV (34.8+/-0.7ms) and FR (35.5+/ 0.8ms). The ECD fits and ROC-r peaks co-localized to within a mean (median) distance of 8.3+/-5.9mm (6.2mm). CONCLUSION: ROC-r volumetric mapping co localized closely with the standard ECD approach. This analysis can be added to any whole-brain MEG source imaging protocol, and is especially useful for single subject mapping. Additionally, the development of FR as an analogue to GoF or CV for volumetric mapping is a critical improvement for clinical applications. PMID- 26993820 TI - The role of diversity in complex ICA algorithms for fMRI analysis. AB - BACKGROUND: The widespread use of data-driven methods, such as independent component analysis (ICA), for the analysis of functional magnetic resonance imaging data (fMRI) has enabled deeper understanding of neural function. However, most popular ICA algorithms for fMRI analysis make several simplifying assumptions, thus ignoring sources of statistical information, types of "diversity," and limiting their performance. NEW METHOD: We propose the use of complex entropy rate bound minimization (CERBM) for the analysis of actual fMRI data in its native, complex, domain. Though CERBM achieves enhanced performance through the exploitation of the three types of diversity inherent to complex fMRI data: noncircularity, non-Gaussianity, and sample-to-sample dependence, CERBM produces results that are more variable than simpler methods. This motivates the development of a minimum spanning tree (MST)-based stability analysis that mitigates the variability of CERBM. COMPARISON WITH EXISTING METHODS: In order to validate our method, we compare the performance of CERBM with the popular CInfomax as well as complex entropy bound minimization (CEBM). RESULTS: We show that by leveraging CERBM and the MST-based stability analysis, we are able to consistently produce components that have a greater number of activated voxels in physically meaningful regions and can more accurately classify patients with schizophrenia than components generated using simpler models. CONCLUSIONS: Our results demonstrate the advantages of using ICA algorithms that can exploit all inherent types of diversity for the analysis of fMRI data when coupled with appropriate stability analyses. PMID- 26993821 TI - Use of XenXTM, the latest ureteric occlusion device with guide wire utility: results from a prospective multicentric comparative study. AB - PURPOSE: This is a prospective multicentric comparative study evaluating the performance of XenX-a new dual-purpose device for the prevention of stone fragments migration during ureteroscopic lithotripsy (URS). METHODS: Between March 2014 and January 2015, 41 patients undertaking URS + XenX were matched with 41 patients undergoing standard URS. Patients included had unilateral ureteric stone(s) of 0.5-1.5 cm in maximum size. Demographics, complication rates and surgical outcomes were recorded for comparison. A Likert-like 5-grade scoring system was used for surgeons' evaluation of XenX properties. Cost analysis was performed by comparing weighted mean costs of the relevant procedures. RESULTS: Patients' characteristics between the two groups were comparable. Lasering time was longer for XenX group (13.59 vs. 5.17 min; p = 0.0001) whilst use of basket and need of JJ stent insertion was more frequent in control group (19.5 vs. 97.6 %; p = 0.0001 and 22 vs. 35 %; p = 0.001, respectively). Intra-operative SFR was significantly higher for XenX group (100 vs. 85.4 %; p = 0.0001), but not at 4 week follow-up, after ancillary procedures were needed in 17.1 % of the control group. Surgeons' evaluations for XenX were suboptimal for "Ease of Basketing" (2/5) and "Advancement of double J stent" (3/5). The use of XenX increased costs of procedures, but spared the costs associated to ancillary procedures and stent removals. CONCLUSIONS: XenX confirmed to be a safe and effective device especially for the treatment of upper ureteric tract stones; moreover, XenX may reduce the risk for the need of auxiliary procedures and for the insertion of a JJ stent. PMID- 26993822 TI - Gastroenterologists Have Suboptimal Hepatitis B Virus Screening Rates in Patients Receiving Immunosuppressive Therapy. AB - BACKGROUND AND AIMS: Hepatitis B reactivation in patients undergoing immunosuppressive therapy can lead to liver failure and death. Prior studies have shown suboptimal hepatitis B screening rates, but few have compared screening rates across specialties or factors associated with screening. METHODS: A retrospective study was performed using a hospital-based chemotherapy database and outpatient pharmacy records from January 1999 to December 2013. HBV screening rates prior to initiation of immunosuppression were determined. Multivariate analysis was used to determine predictors of HBV screening. RESULTS: Of the 4008 study patients, 47 % were screened prior to receiving immunosuppressive therapy; only 48 % on rituximab and 45 % of those on anti-TNF therapy were screened. Transplant specialists screened most frequently (85 %) while gastroenterologists screened the least (34 %). Factors significantly associated with HBV screening were younger age, Asian race, use of anti-rejection therapy, and treatment by a transplant specialist (p < 0.001). CONCLUSION: HBV screening prior to immunosuppressive therapy is suboptimal, especially among gastroenterologists. Efforts to improve screening rates in at risk populations are needed. PMID- 26993824 TI - Portal Hypertension Complications Are Frequently the First Presentation of NAFLD in Patients Undergoing Liver Transplantation Evaluation. AB - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is likely to replace Hepatitis C as the leading cause of cirrhosis resulting in liver transplantation (LT) within a few years. Unfortunately, due to the lack of established guidelines for the screening of NAFLD in high-risk populations, many patients present with portal hypertension complications as their first manifestation of NAFLD require a LT evaluation. We aimed to investigate what proportion of patients who underwent LT for NAFLD-cirrhosis had knowledge of their liver disease prior to presenting with portal hypertension complications and to identify differences in clinical parameters between those with and without knowledge of preexisting NAFLD. METHODS: Consecutive patients who underwent LT for NAFLD-cirrhosis at a tertiary referral center were included in the study. Demographic and clinical data at the time of the first LT evaluation visit were collected, and patient knowledge of previous NAFLD was documented. Ascites, variceal bleeding, hepatic encephalopathy, and thrombocytopenia leading to diagnosis of underlying cirrhosis were considered as the presenting symptoms of portal hypertension. A p < 0.05 was considered statistically significant. RESULTS: A total of 124 subjects who received LT for NAFLD-cirrhosis were included, 58 % (n = 72) were male. At the time of the first LT evaluation visit, 60 % had diabetes, the mean body mass index was 33.2 [28.6, 37.6] kg/m(2), and the mean Model for End-Stage Liver Disease (MELD) score was 14.0 [11.0, 19.0]. More importantly, 85/124 patients (68.5 %) had no knowledge of preexisting NAFLD prior to presentation with symptoms of portal hypertension. The presenting symptoms were new-onset ascites in 61 %, hepatic encephalopathy in 25 %, variceal bleeding in 18 %, thrombocytopenia in 9 %, and other in 9 % (non-exclusive). Patients with no prior knowledge of NAFLD were less likely to have a diagnosis of hypercholesterolemia (30 vs. 50 %, p = 0.035) and had a trend toward having higher MELD scores at the time of the first LT evaluation visit (15 vs. 13.5, p = 0.05) and presenting with encephalopathy (25 vs. 10 %, p = 0.06) compared to those with previous knowledge of NAFLD diagnosis. CONCLUSION: The majority of patients undergoing liver transplant evaluation for NAFLD-cirrhosis are not aware of underlying NAFLD until they present with features of portal hypertension. New guidelines should consider screening for NAFLD in certain high-risk groups as more effective treatments for NAFLD are emerging. PMID- 26993823 TI - Zero-Inflated Models for Identifying Relationships Between Body Mass Index and Gastroesophageal Reflux Symptoms: A Nationwide Population-Based Study in China. AB - BACKGROUND AND AIM: That obesity leads to gastroesophageal reflux is a widespread notion. However, scientific evidence for this association is limited, with no rigorous epidemiological approach conducted to address this question. This study examined the relationship between body mass index (BMI) and gastroesophageal reflux symptoms in a large population-representative sample from China. METHODS: We performed a cross-sectional study in an age- and gender-stratified random sample of the population of five central regions in China. Participants aged 18 80 years completed a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire. The zero-inflated Poisson regression model estimated the relationship between body mass index and gastroesophageal reflux symptoms. RESULTS: Overall, 16,091 (89.4 %) of the 18,000 eligible participants responded. 638 (3.97 %) and 1738 (10.81 %) experienced at least weekly heartburn and weekly acid regurgitation, respectively. After adjusting for potential risk factors in the zero-inflated part, the frequency [odds ratio (OR) 0.66, 95 % confidence interval (95 % CI) 0.50-0.86, p = 0.002] and severity (OR 0.66, 95 % CI 0.50-088, p = 0.004) of heartburn in obese participants were statistically significant compared to those in normal participants. In the Poisson part, the frequency of acid regurgitation, overweight (OR 1.10, 95 % CI 1.01-1.21, p = 0.038) and obesity (OR 1.19, 95 % CI 1.04-1.37, p = 0.013) were statistically significant. BMI was strongly and positively related to the frequency and severity of gastroesophageal reflux symptoms. Additionally, gender exerted strong specific effects on the relationship between BMI and gastroesophageal reflux symptoms. CONCLUSIONS: The severity and frequency of heartburn were positively correlated with obesity. This relationship was presented distinct in male participants only. PMID- 26993825 TI - Significant Association Between Gallstone Disease and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are common digestive disorders worldwide. Both conditions share certain risk factors including obesity, insulin resistance and diabetes. Several epidemiologic studies have reported the relationship between these two conditions. AIM: We conducted a systematic review and meta-analysis to characterize the association between GD and NAFLD. METHODS: A comprehensive search of the databases MEDLINE and EMBASE was performed from inception through November 2015. The inclusion criterion was the observational studies' assessment of the association between GD and NAFLD in adult participants. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using a random-effects model. RESULTS: Data were extracted from 12 observational studies (9 cross-sectional studies, 1 case control study and 2 cohort studies). The pooled OR of NAFLD in patients who had GD was 1.55 (95 % CI 1.31-1.82). The statistical between-studies heterogeneity (I (2)) was 64 %. The association remained significant when limited to cohort studies with pooled OR 1.33 (95 % CI 1.14-1.55, I (2) = 0 %). CONCLUSION: Our meta-analysis demonstrated that GD is significantly associated with NAFLD. Further prospective studies exploring the underlying mechanism of this association should be pursued. PMID- 26993826 TI - CHST11/13 Regulate the Metastasis and Chemosensitivity of Human Hepatocellular Carcinoma Cells Via Mitogen-Activated Protein Kinase Pathway. AB - BACKGROUND: Carbohydrate sulfotransferases 11-13 (CHST11-13), that catalyze the transfer of sulfate to position 4 of the GalNAc residue of chondroitin, have been implicated in various diseases. AIM: This study aimed to clarify the association of CHST11-13 expression with metastasis and drug sensitivity in hepatocellular carcinoma (HCC) cells. METHODS: We measured the levels of CHST11 and CHST13 in a series of HCC cells using real-time PCR and Western blotting. After RNAi and forced expression treatment of CHST11 and CHST13 in MHCC97L and MHCC97H cells, metastatic potential and drug sensitivity of the two cells were investigated with ECM invasion assay, drug sensitivity assay, and in vivo antitumor activity assay. By real-time PCR and Western blotting, we explored the possible impacts of these two genes on mitogen-activated protein kinase (MAPK) signal pathway. MAPK pathway was blocked by PD98059 or SP600125 to elucidate the effects of MAPK pathway on metastasis and chemosensitivity. RESULTS: Significantly reduced levels of CHST11 and CHST13 were observed in highly invasive MHCC97H cells compared with those of MHCC97L cell line with low metastatic potential. Decreased or forced expression of CHST11 and CHST13 altered metastatic potential and drug sensitivity of MHCC97L and MHCC97H cells. Remarkable alteration of MAPK activity was shown in two HCC cells with genetic manipulation. Conversely, pharmacologic inhibition of the MAPK pathway suppressed invasive potential and rescued drug sensitivity of MHCC97H cells. CONCLUSIONS: Our results have demonstrated that CHST11 and CHST13 negatively modulate metastasis and drug resistance of HCC cells probably via oncogenic MAPK signal pathway. PMID- 26993828 TI - Abstracts of the 22nd Scientific Conference of the Society on Neuroimmune Pharmacology. PMID- 26993827 TI - Health Care Usage and Related Costs in Fibular Plating for AO Type 44-B Ankle Fractures in a Belgian University Hospital: An Exploratory Analysis. AB - Open reposition and internal fixation (ORIF) is the reference standard for unstable Arbeitsgemeinschaft fur Osteosynthesefragen (AO)-type 44-B ankle fractures. Age, comorbidity, delayed-staged surgery, and length-of-stay (LOS) are all factors that presumably correlate positively with health care costs. We performed an exploratory analysis of the health care costs associated with the treatment of this type of fracture and hypothesized that these costs will be significantly greater for the elderly. A total of 217 patients with an acute AO type 44-B ankle fracture were included. We studied 14 variables, and 5 main cost categories were defined. The health care costs associated with the treatment of ankle fractures in the present study constituted more than one half (53%) of the hospitalization costs, which, in turn, were strongly related to the LOS. Delayed staged surgery and age were the most important clinical variables driving the total health care costs and LOS (p < .001). The median LOS before ORIF was 6 times greater (12 versus 2 days) for patients treated using a delayed-staged surgery protocol. The cutoff age above which the costs differed significantly was 65 years. Thus, the median total health care costs for the treatment of these fractures were doubled in the older group ($9207 versus $4559), mainly owing to a 2 times greater LOS before ORIF (2 versus 4 days) and 3 times greater total LOS (4 versus 12.5 days) in the elderly. Surprisingly, the complication rate was equal (27.7% versus 29.3%) in the 2 groups. Therefore, to decrease the total health care costs, we should focus on a reduction of the costly LOS before ORIF in the elderly population. PMID- 26993831 TI - Inferior vena cava filter retrieval provides no advantage in the average patient. AB - BACKGROUND: Inferior vena cava (IVC) filter placement is performed to mitigate the risk of pulmonary embolism (PE) when anticoagulation is contraindicated or ineffective. Technical advances now allow catheter-based filter retrieval. Many believe the benefits of retrieval are self-evident, yet retrieval carries an inherent complication risk and cost. The purpose of this study was to quantitatively weigh the risks and benefits of IVC filter retrieval using formal decision analysis. METHODS: A Markov state-transition model was used to simulate two clinical scenarios: to leave a previously placed IVC filter or to retrieve it. Analysis was performed during the lifetime of the individual, and outcomes were expressed in quality-adjusted life-years (QALYs). The base case is a 60-year old man with a filter placed within 3 months who no longer requires mechanical thromboprophylaxis. Potential events included PE, filter complications, and death from all other causes during each cycle. Tolls were used to incorporate the disutility of short-term treatment for PE and filter complications. For the base case and sensitivity analyses, we used utilities and probabilities derived from the literature. RESULTS: In the base case scenario, leaving the filter in place was preferred to filter retrieval, yielding 22.3 vs 21.9 QALYs. One-way sensitivity analysis demonstrated that filter retrieval may be preferable if the utility of living with a filter is <0.98. For all probabilities of retrieval and PE mortality, leaving the filter in place is preferred. CONCLUSIONS: Leaving a previously placed IVC filter provides a 0.4 QALY benefit over retrieving the filter for the average patient. This decision is sensitive to the utility of living with the IVC filter. PMID- 26993829 TI - Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices. AB - In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood. To address this issue, whole-cell recordings were performed on young (14-24 day old) C57BL/6J mice. We investigated the actions of the synthetic cannabinoid WIN55,212-2 (1 MUM) and the endocannabinoid N arachidonoyl ethanolamine (anandamide; AEA, 1 MUM) in the presence of HIV-1 Tat on GABAergic neurotransmission in mouse prefrontal cortex (PFC) slices. We found a Tat concentration-dependent (5-50 nM) decrease in the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). The cannabinoid 1 receptor (CB1R) antagonist rimonabant (1 MUM) and zero extracellular calcium prevented the significant Tat-induced decrease in mIPSCs. Further, bath-applied WIN55,212-2 or AEA by itself, significantly decreased the frequency, but not amplitude of mIPSCs and/or spontaneous IPSCs (sIPSCs), and occluded a further downregulation of IPSCs by Tat. Pretreatment with rimonabant but not the CB2R antagonist AM630 (1 MUM) prevented the WIN55,212-2- and AEA-induced decrease in IPSCs frequency without any further Tat effect. Results indicated a Tat-induced decrease in GABAergic neurotransmission, which was occluded by cannabinoids via a CB1R-related mechanism. Understanding the relationship between Tat toxicity and endocannabinoid signaling has the potential to identify novel therapeutic interventions to benefit individuals suffering from HAND and other cognitive impairments. PMID- 26993832 TI - Changes in the diameter and valve closure time of leg veins in primigravida women during pregnancy. AB - OBJECTIVE: The aim of this study was to monitor the changes that develop in leg veins of primigravida women during pregnancy. METHODS: Sixty primigravida women volunteered to undergo clinical evaluation and duplex ultrasound examination of both lower limb veins to monitor changes in vein diameter and valve closure time (VCT) during pregnancy and 3 months postpartum by duplex ultrasound. A total of four readings were taken for each subject, one reading for each trimester and the last reading at 3 months postpartum. RESULTS: The mean (+/- standard deviation) age of participants was 26.82 +/- 2.47 years; 39 limbs (32.5%) and 65 limbs (54.2%) developed C1-C3 venous changes during the second and third trimesters, respectively. Three months post partum, 36 limbs (30%) continued to have C1-C2 changes. Only four limbs in four subjects developed varicose veins along the great saphenous vein, and their VCT was more than 1 second. These subjects were found to have a family history of varicose veins. Duplex examinations showed that there was a gradual increase in the diameter and VCT from the second trimester through the third trimester of pregnancy in all examined venous segments. These changes were statistically significant by Friedman and related-samples Wilcoxon signed rank tests within the same legs (P = .001) but not between legs in the same subject (P > .05), even with adjustment for body mass index (P = .001-.049). CONCLUSIONS: In primigravida women, lower limb veins showed gradual increase in vein diameter and in VCT starting from the second trimester. These changes reverted to baseline in most cases 3 months after delivery. PMID- 26993833 TI - Superficial venous reflux duration and cessation with two concurrent duplex probes. AB - BACKGROUND: Venous reflux is the principal hemodynamic disorder and therapeutic target in patients with superficial venous insufficiency. To date, no studies have identified where or when it stops, anatomically or regionally, along the course of the refluxive conduit. Duplex measurements of reflux are performed invariably with a single probe. Because many anatomic locations are studied, repeated provocation maneuvers are required. However, this fails to appreciate reflux as a circulation. The use of two probes placed concurrently in different regions may address this limitation. The study compared venous reflux duration and cessation, above the knee and below the knee simultaneously, with two duplex probes. METHODS: Seventeen legs from 17 consecutive patients (12 female, nine left) with great saphenous vein reflux were studied. Their median (range) age was 51 (28-71) years; weight, 76.8 (63.5-189) kg; height, 169 (153-180) cm; and Venous Clinical Severity Score, 5 (1-12). The clinical class of the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification was as follows: C2, 6; C3, 4; C4a, 5; and C4b, 2. After 2 minutes of elevation, the leg was assessed for reflux duration with duplex ultrasound. This occurred when the patient stood up during venous filling. One probe was positioned 10 cm below the saphenofemoral junction over the great saphenous vein (point A) and the other over a refluxive saphenous vein or tributary below the knee (point B). Concurrent images were displayed on adjacent monitors and recorded by a single video camera. Reflux duration was from the onset of dependency, indicated by the start of the video, to the termination of the red color (reflux) on video playback. The probes were swapped to negate for differences in machine sensitivity. Each leg was tested three times. Simultaneous was defined when there was <0.1 second difference between the two sites. RESULTS: The median (range) vein diameters at points A and B were 6.1 (2.8-9.3) mm and 5.5 (2.5-8.1) mm, respectively, with an intertransducer distance of 41 (23-59) cm. There was no significant difference in reflux duration between point A with 27 (9-150) seconds and point B with 27 (10 149) seconds (P = .943 [Wilcoxon]). The correlation was excellent (r = .986; P < .0005 [Spearman]). CONCLUSIONS: This is the first study to investigate reflux cessation by introducing a novel two-probe technique. It has demonstrated that reflux may stop simultaneously above and below the knee with use of the elevation to dependency maneuver to provoke reflux. It has shown that either site may be used to measure reflux duration. Furthermore, the two-probe technique confirms the belief that the mechanism of refluxive venous filling is through the descending path of a recirculation circuit. PMID- 26993834 TI - Relative importance of iliac vein obstruction in patients with post-thrombotic femoral vein occlusion. AB - BACKGROUND: Patients with femoral vein occlusion rapidly develop collateral flow through the deep femoral vein, an embryonic collateral. In contrast, iliac vein collateralization is sparser and functionally poorer. It is not uncommon to have femoral vein occlusions associated with iliac vein obstruction, even though the femoral vein occlusion is often more readily apparent on venograms and duplex scans, whereas the iliac vein obstruction may remain occult. We examined whether percutaneous stent correction of iliac vein obstruction associated with femoral vein occlusions would yield symptomatic relief. METHODS: During a 13-year period, 39 patients with femoral vein occlusions underwent stenting of associated iliac vein stenoses. RESULTS: Median age was 51 years (17-86 years). The male-to-female and right-to-left ratios were 1:3 and 1:2, respectively. The clinical class of the Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification was as follows: C0-2 (with pain), two of 39 (5%); C3, 19 of 39 (48%); C4, 10 of 39 (26%); C5, one of 39 (3%); and C6, seven of 39 (18%). Concurrent ablation of a refluxive saphenous vein was performed in seven of 39 (18%). Reintervention was carried out in 14 of 39 limbs (36%). Median follow-up was 26 months (1-154 months). Median iliac vein stenosis was 80% (40%-100%). Primary, primary assisted, and secondary patency rates at 2 years were 57%, 88%, and 96%, respectively. Pain grade (visual analog scale, 0-10) improved from median 5 (0-9) to 3 (0-8) after stenting (P < .03); 12% were completely relieved of pain. Cumulative improvement in pain (>= 3 of 10 on the visual analog scale) was 87% at 2 years. Median swelling (grade 0, none; grade 1, pitting; grade 2, ankle edema; grade 3, gross) improved from median 3/3 (0-3) to 2/3 (0-3) (P = .09, NS). Among 22 of 39 limbs (56%) with grade 3 swelling before stenting, seven of 22 limbs (32%) with grade 3 swelling improved (>= 1 grade) after stent placement. In the 15 of 22 limbs (68%) with residual grade 3 swelling after stenting, subjective improvement was reported by all. Four of seven active ulcers (54%) healed. There were no obstructive sequelae after concurrent saphenous ablation. Saphenous flow in the erect position was not different from that of controls with patent femoral veins. CONCLUSIONS: Percutaneous stenting of associated iliac vein obstruction in symptomatic limbs with femoral vein occlusion yields satisfactory clinical relief. The saphenous vein has little collateral role in this pathologic process and can be safely ablated if it is refluxive, in line with prior observations. PMID- 26993830 TI - Subsequent arterial ischemic events in patients receiving anticoagulant therapy for venous thromboembolism. AB - OBJECTIVE: Patients with acute venous thromboembolism (VTE) are at increased risk for the development of subsequent arterial ischemic events unrelated to the diagnosis of VTE. Accurate identification of VTE patients at increased risk for ischemic events during the course of anticoagulation may help to select those who would potentially benefit from concomitant therapy with anticoagulants and antiplatelets. METHODS: We used the Registro Informatizado de Enfermedad TromboEmbolica (RIETE) Registry to assess the rate and severity of subsequent ischemic events (ie, stroke, myocardial infarction, lower limb amputation, or mesenteric ischemia) appearing during the course of anticoagulant therapy and tried to identify risk factors for these events. RESULTS: From February 2009 to March 2014, 23,370 patients were recruited: 12,397 initially presenting with pulmonary embolism (PE) and 10,973 with deep venous thrombosis. During the course of anticoagulation (mean, 9.2 months), 597 patients developed recurrent VTE, 652 bled, 162 had ischemic events (stroke, 86; myocardial infarction, 53; limb amputation, 13; mesenteric ischemia, 11), and 2063 died. Of these, 29 patients died of recurrent PE, 83 of bleeding, and 53 of the ischemic events. On multivariable analysis, cancer (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.21-2.61), chronic lung disease (HR, 1.54; 95% CI, 1.05-2.26), renal insufficiency (HR, 1.72; 95% CI, 1.25-2.36), anemia (HR, 1.54; 95% CI, 1.11 2.14), prior artery disease (HR, 1.84; 95% CI, 1.29-2.64), and diabetes (HR, 1.58; 95% CI, 1.10-2.27) independently predicted the risk for ischemic events. Most of these variables also predicted major bleeding (cancer, chronic lung disease, renal insufficiency, anemia, and prior artery disease) or recurrent PE (cancer, chronic lung disease, anemia, and prior artery disease). CONCLUSIONS: In patients receiving anticoagulation for VTE, the mortality due to PE recurrences was lower than the mortality due to ischemic events. Most independent predictors for ischemic events were also predictors for major bleeding and for recurrent PE. PMID- 26993835 TI - The effect of stent placement for May-Thurner syndrome combined with symptomatic superficial venous reflux disease. AB - OBJECTIVE: The current study aimed to determine whether it is necessary to correct May-Thurner syndrome (MTS) simultaneously with superficial venous reflux disease (S-VRD) in limbs of combined symptomatic MTS/S-VRD. METHODS: A retrospective analysis of patients with S-VRD combined with MTS was conducted in a single institution from January 2001 to December 2010. Doppler ultrasound and phlebography were performed in patients with VRD. Computed tomography angiography or transfemoral venography was selectively performed in patients with severe symptoms or findings on phlebography suggestive of MTS. MTS was found in 207 patients. Among these, 121 patients were successfully treated with stent placement combined with endovenous laser ablation (EVLA); the remaining 86 patients, who were treated with EVLA for S-VRD alone, served as a control group. Clinical results, venous reflux, and quality of life were evaluated before and after treatment. Stent patency was followed up with Doppler ultrasound. RESULTS: There was no significant difference in age, female to male ratio, clinical symptoms, comorbidities, or percentage with S-VRD between the two groups. A total of 125 stents were placed in 121 patients in the EVLA + stent group. The rate of technical success was 100%. Follow-up periods ranged from 1 to 91 months (mean, 70.4 +/- 21.3 months). The 4-year primary patency rate was 93.3%. The incidence of pain, edema, and ulceration was decreased significantly in the stent + EVLA group. However, there was a high rate of S-VRD recurrence in the EVLA-alone group. Quality of life improved significantly in the EVLA + stent group; improvements included relief of pain, edema, and fatigue and increased physical activity. For deep venous reflux, there was no significant improvement after stent placement for MTS. CONCLUSIONS: Stent placement is an effective and durable treatment of MTS combined with symptomatic S-VRD; it results in a high level of long-term patency and a significant relief of pain, edema, and ulceration. Furthermore, correction of MTS plays an important role in decreasing the recurrence rate of S-VRD after EVLA. PMID- 26993836 TI - Utilization of venous duplex scanning and postoperative venography in patients with subclavian vein thrombosis. AB - OBJECTIVE: The purpose of this study was to review preoperative and postoperative duplex scans and postoperative venograms in patients with subclavian vein thrombosis who underwent first rib resection and scalenectomy (FRRS) during 2005 to 2013. METHODS: Preoperative venous duplex scans revealed no compression (NC), venous compression (VC, >= 50% decrease in velocity on abduction), venous ablation (VA, 0 velocity on abduction), and acute thrombus (AT, 0 velocity on abduction and adduction). Correlation with 2-week postoperative venograms (open, stenosis requiring dilation, or occluded) and postoperative (2- to 4-month, 6- to 8-month, and 12-month) duplex scans was performed. RESULTS: Of 215 patients treated with FRRS for effort thrombosis, 140 had an ipsilateral preoperative duplex scan and postoperative venogram. Twenty-nine patients (21%) had VC, 70 (50%) had VA, 8 (5.7%) had AT, and 33 (24%) had NC. Patients with preoperative NC or VC were more likely to have an open vein on venography (P = .014). Six to 8 months after FRRS, patients with preoperative VA were more likely to have compression or ablation (P = .009); no difference was seen at 1 year. Patency rates at last follow-up were 100% in the preoperative VC and AT groups, 96% in those with VA, and 94% in patients with no preoperative compression. The 128 preoperative scans of the asymptomatic side revealed that 67 patients (52%) had NC, 29 (23%) had VC, 32 (25%) had VA, and 0 had AT. Patients with NC (P = .027), VC (P = .017), or VA (P = .008) were significantly more likely to have the same result on the opposite side. CONCLUSIONS: Postoperative duplex scans reveal that VC and VA resolve during the year after FRRS, obviating the need for repeated venography or intervention. Patency rates are excellent in all patients when postoperative venography directs intervention. Patients with NC, VC, or VA on preoperative scans often show the same result on the opposite side. PMID- 26993837 TI - Embolization techniques for high-flow arteriovenous malformations with a dominant outflow vein. AB - OBJECTIVE: The aim of this study was to assess the management and outcomes of arteriovenous malformations (AVMs) with a dominant outflow vein (DOV) treated with retrograde venous embolization. METHODS: A retrospective review was performed from November 2010 to May 2014 on all patients with a high-flow AVM and associated DOV who underwent transvenous embolization of the DOV. Indications, techniques, complications, and outcomes were reviewed. RESULTS: Fourteen patients (five male; 36%) underwent transvenous embolization of high-flow AVMs with a DOV. Median age was 41.6 years (15.7-65.8 years). The AVM was located on an extremity in eight patients (57%) and in the pelvis in six patients (43%). The indication for the procedure was pain in 11 patients (79%), swelling in 3 patients (21%), a nonhealing wound in 1 patient (7%), and impotence in 1 patient (7%). The median number of prior procedures to treat the AVM was 2.5 (0-13). Transvenous embolization with coils was performed in 13 patients (93%). The Amplatzer vascular plug and Amplatzer septal occluder (St. Jude Medical, St. Paul, Minn) were used in four patients (29%). Concurrent percutaneous puncture embolization of the AVM nidus was used in seven patients (50%) and transcatheter arterial embolization in eight patients (57%). Technical angiographic success was seen in all patients. Five patients (36%) experienced a complete response to treatment, whereas eight (57%) experienced a partial response. Seven patients (50%) required further procedures for residual symptoms. CONCLUSIONS: AVMs with a DOV can be successfully treated by a transvenous approach. Percutaneous puncture embolization of the nidus or draining vein and transcatheter arterial embolization may assist in reducing flow. PMID- 26993838 TI - Venous duplex and pathologic differences in thrombus characteristics between de novo deep vein thrombi and endovenous heat-induced thrombi. AB - OBJECTIVE: Superficial venous reflux disease has been treated with endovenous ablation techniques for more than 15 years. Thrombi discovered in the postoperative period are referred to as endovenous heat-induced thrombi (EHIT). In spite of the few studies of the ultrasound differentiation between EHIT and deep vein thrombi (DVT), there remains a paucity of literature regarding the evaluation of ultrasound examination and pathologic differentiation. METHODS: Six Yorkshire cross swine underwent femoral vein thrombosis by suture ligation or endovenous radiofrequency ablation. At 1 week after the procedure, each femoral vein was imaged by color Duplex ultrasound and sent for histologic interpretation for differentiation between EHIT and DVT. Five blinded vascular surgery faculty, two vascular surgery fellows, and three vascular surgery residents reviewed the ultrasound images. RESULTS: Thrombi associated with radiofrequency ablation demonstrated a greater degree of hypercellular response, fibroblastic reaction, and edema (3.42 vs 2.92; 3.75 vs 2.42; 2.83 vs 1.33). Specimens harvested from the iatrogenic-induced DVT swine demonstrated a more prolific response to trichrome staining (3.42 vs 2.67). Evidence of revascularization was found in all of the EHIT specimens but in 33% of DVT specimens. On the basis of histologic findings, the pathologist predicted correct modality 92% of the time. Subgroup analysis comparing paired specimens from each swine failed to demonstrate any marked pathologic differences. Recorded ultrasound images from EHIT and DVT samples were reviewed by fellows, residents, and vascular surgery staff to determine whether clot was stationary or free-floating (n = 111; 93%), evidence of retracted or adherent vein (n = 105; 88%), and absence of color flow (n = 102; 85%). The degree of occlusion (partial vs total) and degree of distention of a visualized vein were least likely to be agreed on by reviewers (n = 95; 79% each, respectively). In subgroup (DVT vs EHIT) analyses, the percentage agreement was greatest among vascular surgery fellows (89% and 92%) compared with residents (82% and 79%) and faculty (78% and 77%). CONCLUSIONS: It is possible to differentiate the thrombus origin on pathologic examination but not clinically on ultrasound. Wide variability exists for ultrasound diagnosis of EHIT and de novo DVT. Care must be taken in evaluating post-treatment duplex scans to not assign diagnosis of EHIT when DVT may well be present and extending into the deep venous system. The modulation of collagen production in the treatment of DVT may be helpful in preventing vascular dysfunction and reducing the post-thrombotic changes. Further studies on injury after radiofrequency ablation and laser ablation are needed. PMID- 26993840 TI - Endovascular treatment of acute renal failure secondary to caval thrombosis and suprarenal filter migration. AB - Although inferior vena cava filter placement is a safe and effective method of reducing the risk of pulmonary embolism, devastating complications can result from thrombosis and migration. Here we present a case of acute renal failure as a result of suprarenal inferior vena cava filter migration and caval thrombosis. We discuss a novel endovascular approach for its management by mechanical aspirational thrombectomy. PMID- 26993839 TI - The soluble urokinase plasminogen activator receptor and its fragments in venous ulcers. AB - OBJECTIVE: Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic functions that include chemotaxis, adhesion, and proliferation, which also have a role in wound healing. The aim of this study was to determine whether suPAR and its cleaved fragments are present in venous ulcers and whether their levels are associated with healing. METHODS: Ulcer exudates were collected from patients with venous leg ulcers (n = 30). Healing was defined as complete re-epithelialization within 6 months of compression therapy. Time-resolved fluorescence immunoassays were validated for quantification of suPAR and its fragments in ulcer exudates. The effect of exudates on keratinocyte migration was analyzed by an in vitro scratch assay. RESULTS: Ulcer exudates from patients who healed (n = 9) had approximately threefold higher levels of intact suPAR (P = .005), twofold higher levels of suPARI (P = .03), and approximately threefold higher levels suPARII-III (P < .0001) compared with nonhealers (n = 21). Exudate from healing ulcers stimulated keratinocyte migration (P = .02), whereas depletion of suPAR from exudates resulted in cell apoptosis. CONCLUSIONS: We conclude that suPAR and its fragments are present in the environs of venous ulcers and may act as indicators of the propensity of venous ulcers to heal, with suPARII-III being the best discriminator. We speculate that suPAR and its fragments may have a role in the maintenance of an optimal ulcer-healing environment. PMID- 26993841 TI - Open surgical removal of retained and dislodged inferior vena cava filters. AB - Retained inferior vena cava (IVC) filters can lead to significant complications. Six patients underwent open surgical removal of complicated IVC filters that could not be removed endovascularly. Struts of the filter perforated the IVC wall in all patients and the adjacent viscera in five. Caval clamping and longitudinal cavotomy with direct closure were used in two patients to remove permanent filters. IVC clamping was not needed in three patients, in whom the filter was first collapsed and then removed through a stab venotomy in the IVC (n = 2) or lumbar vein (n = 1). A broken strut that infected the vertebra was removed outside the IVC in the sixth patient. No early or delayed complications, venous thrombosis, or pulmonary embolism was encountered at a mean follow-up of 1.3 years. PMID- 26993842 TI - Management of an enormous arteriovenous malformation. PMID- 26993843 TI - Multidisciplinary treatment of extremity arteriovenous malformations. AB - Congenital vascular malformations (CVMs) are a complex group of lesions that arise by embryologic dysmorphogenesis without increased endothelial proliferation that leads to structural and functional anomalies of the vascular system characterized by a wide range of presenting symptoms and often unpredictable clinical course. A recent advancement in the diagnostic and treatment modalities has resulted in a better understanding of the pathophysiology and natural history of CVMs and improved management of these lesions. The multidisciplinary approach and diagnostic algorithm used to distinguish high-flow (HFVM) from low-flow vascular malformations (LFVM) have been validated as clinically applicable for making an accurate anatomic and hemodynamic diagnosis of CVMs; they serve as a basis for proper treatment selection and significantly facilitate communication among different medical specialists. Dynamic contrast-enhanced magnetic resonance imaging is able to definitively distinguish HFVM from LFVM with accuracy of approximately 84%. In inconclusive cases, confirmatory angiography is required. Symptomatic, diffuse, extensive, macrocystic LFVMs and LFVMs that involve multiple tissue planes and vital structures are best treated with foam sclerotherapy. Primary surgical resection is the treatment of choice for localized, septated, and microcystic LFVMs. The management of HFVMs is characterized by multimodal treatment including preoperative embolization followed by complete surgical resection or sclerotherapy of the remaining venous component. Treatment of extensive CVMs is palliative and goal oriented. Implementation of the proposed diagnostic protocols and therapeutic algorithms in a multidisciplinary setting results in favorable outcomes with acceptable complication rates in this challenging patient population. PMID- 26993844 TI - Health-related quality-of-life scales specific for chronic venous disorders of the lower limbs. AB - OBJECTIVE: We conducted a systematic review of the literature about quality-of life (QOL) scales in chronic venous disorders (CVDs) comprising leg ulcers to identify the respective advantages and deficits of existing tools. METHODS: A research protocol was built following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the PICO (population, intervention, comparator, and outcome) criteria. The following databases were screened: MEDLINE, SCOPUS, EMBASE, CINHAL, and Cochrane. Psychometric and linguistic validation studies in English were included, as were clinical trials that have used QOL scales in CVDs. The data search was up to date as of October 31, 2013. RESULTS: Inclusion criteria were met in 103 of the 511 recorded references, in which 10 scales were identified: two for the full spectrum of CVDs, three for patients with CVDs without leg ulceration, four for leg ulcers, and one exclusively for patients with varicose veins. Among them, the ChronIc Venous Insufficiency Questionnaire (CIVIQ), Aberdeen Varicose Vein Questionnaire (AVVQ), and VEnous INsufficiency Epidemiological and Economic Study on Quality of Life (VEINES-QOL) scales were the most highly used according to the literature, and CIVIQ and VEINES-QOL were the most extensively validated scales and had the longest iterative validation process. A total of 31 psychometric and linguistic validations of the 10 QOL scales and 66 clinical trials that have used these scales were identified. The validation studies were based on acceptability, content validity, construct validity, reliability, and responsiveness. The clinical trials were composed of 25 randomized controlled trials and 41 observational studies. Only the randomized controlled trials are considered in the present article. CONCLUSIONS: This systematic review confirmed that CVDs have an important effect on QOL. The majority of the studies addressed the application rather than the validation of the 10 identified scales. Two scales, CIVIQ and VEINES-QOL, emerged as being thoroughly validated instruments, although factorial stability was not demonstrated for the VEINES-QOL. Our findings confirm a paucity of validation studies. PMID- 26993845 TI - Thrombophilia testing has limited usefulness in clinical decision-making and should be used selectively. AB - Management of venous thromboembolism (VTE) includes evaluation for hypercoagulable state, especially if the VTE occurs in young patients, is recurrent, or is associated with a positive family history. These laboratory tests are costly, and surprisingly, there is little evidence showing that testing leads to improved clinical outcomes. Evidence based on observational prospective studies suggests that optimal duration of anticoagulation should be based on clinical risks resulting in VTE, such as transient, permanent, and idiopathic or unprovoked risks, and less on abnormal thrombophilia values. Thrombophilia screening is important in a subgroup of clinical scenarios, such as when there is clinical suspicion of antiphospholipid antibody syndrome, heparin resistance, or warfarin necrosis; with thrombosis occurring in unusual sites (such as mesenteric or cerebral deep venous thrombosis); and for pregnant women or those seeking pregnancy or considering estrogen-based agents. Thrombophilia screening is not likely to be helpful in most cases of first-time unprovoked VTE in the setting of transient risks, active malignant disease, deep venous thrombosis of upper extremity veins or from central lines, two or more VTEs, or arterial thrombosis with pre-existing atherosclerotic risk factors. The desire by both patient and physician for a scientific explanation of the clotting event may alone lead to testing, and if so, it should be with the understanding that an abnormal test result will likely not change management, and normal results do not accurately exclude a thrombophilic defect because there are likely factors yet to be discovered. Such false assumptions may lead to shorter durations of treatment than are optimal. PMID- 26993846 TI - Benefit of anticoagulation for the treatment of lower extremity superficial venous thrombosis. AB - Superficial venous thrombosis (SVT) of the lower extremity is an acute disorder characterized by thrombosis and inflammation of superficial veins. This most commonly affects varicose veins but can also occur in patients with nonvaricose veins, who may have an underlying condition such as a malignant disease or thrombophilia. It is important to be aware that SVT confers a significant risk for the development of the more serious and debilitating condition of deep venous thrombosis and the potentially life-threatening condition of pulmonary embolism. Recognition of SVT, determination of appropriateness of therapy, and institution of timely therapy are paramount to prevention of deep venous thrombosis and pulmonary embolism in properly selected patients. The objective of this evidence based summary was to provide clinically applicable information from the current literature and guidelines regarding the best treatment options for SVT. There are no randomized trials that compare the efficacy and outcomes of newer therapies, such as the novel oral anticoagulants and endovenous ablation, with traditional therapies, such as traditional anticoagulant and surgery exclusion, in the treatment of SVT. PMID- 26993850 TI - Probing Beneath the Surface: Discovering O-GlcNAc on Intracellular Proteins. PMID- 26993851 TI - Identification and characterization of the protein-associated splicing factor as a negative co-regulator of the progesterone receptor. PMID- 26993852 TI - Language and reading development in the brain today: neuromarkers and the case for prediction. AB - OBJECTIVES: The goal of this article is to provide an account of language development in the brain using the new information about brain function gleaned from cognitive neuroscience. This account goes beyond describing the association between language and specific brain areas to advocate the possibility of predicting language outcomes using brain-imaging data. The goal is to address the current evidence about language development in the brain and prediction of language outcomes. SOURCES: Recent studies will be discussed in the light of the evidence generated for predicting language outcomes and using new methods of analysis of brain data. SUMMARY OF THE DATA: The present account of brain behavior will address: (1) the development of a hardwired brain circuit for spoken language; (2) the neural adaptation that follows reading instruction and fosters the "grafting" of visual processing areas of the brain onto the hardwired circuit of spoken language; and (3) the prediction of language development and the possibility of translational neuroscience. CONCLUSIONS: Brain imaging has allowed for the identification of neural indices (neuromarkers) that reflect typical and atypical language development; the possibility of predicting risk for language disorders has emerged. A mandate to develop a bridge between neuroscience and health and cognition-related outcomes may pave the way for translational neuroscience. PMID- 26993853 TI - Four-part fractures treated with a reversed total shoulder prosthesis: Prospective and retrospective multicenter study. Results and complications. AB - INTRODUCTION: The reversed shoulder prosthesis is becoming the gold standard for cases of complex fracture of the proximal humerus after 70 years of age. MATERIAL AND METHODS: The French Society of Orthopaedic and Traumatology Surgery (SOFCOT) conducted a prospective and retrospective multicenter study to evaluate the results of the reversed shoulder prosthesis implanted in patients with a four part fracture in nine centers. In the retrospective study (n=41 patients, 78 years of age, 14% ASA grade 3, 21% associated fractures) and in the prospective study (n=32 patients, 79 years of age, 37% ASA grade 3, 21% associated fractures) evaluation by independent surgeons was conducted to measure the QuickDASH score, the Constant score, the SSV (subjective shoulder value), and complications to correlate these measurements with radiological results. RESULTS: In both studies, use of an autograft (75%) to perform an osteosuture of tuberosities (90%) and no postoperative immobilization (75%) were similar. In the retrospective study at 39 months (range: 24-62 months) of follow-up, the QuickDASH reached 28 (range: 0 59), the Constant scores (raw Constant=57, weighted Constant=83.4%), and SSV 75 (range: 35-100). Complications after the 1st month (7%) were nonunion or ossifications. In the prospective study at 11 months (range: 5-16.5 months) of follow-up, the QuickDASH reached 40 (range: 1-75), the Constant scores 50 (raw Constant) and 74.6% (weighted Constant), and SSV 69 (range: 10-100). Complications after the 1st month (21%) were stiffness and dislocation, with two patients who underwent revision surgery. In both studies, early complications reached 6% (palsy, dislocation). CONCLUSION: This double (retrospective and prospective) study confirms the good results with a low level of complications of the reversed implant in cases of fracture but with osteosuture of tuberosities. PMID- 26993854 TI - Bennett fracture: Arthroscopically assisted percutaneous screw fixation versus open surgery: Functional and radiological outcomes. AB - BACKGROUND: Arthroscopically assisted percutaneous screw fixation has been introduced to decrease the invasiveness of treatments for intra-articular fractures. HYPOTHESIS: Arthroscopically assisted percutaneous screw fixation of Bennett fracture simplifies the postoperative course compared to open surgery. MATERIAL AND METHODS: Twenty-one Bennett fractures detaching at least one-third of the joint surface were studied retrospectively. Among them, 11 were managed by percutaneous screw fixation and 10 by open surgery. Follow-up was at least 12 months. Clinical and radiological evaluations were performed to assess the development of complications, tourniquet time, immobilisation time, sick-leave time, QuickDASH score, Kapandji score, grip strength, pinch strength, return to work activities, intra-articular screw migration, inadequate reduction, non union, and joint remodelling. RESULTS: The percutaneous group had significantly shorter immobilisation (P<0.0001) and tourniquet (P=0.0068) times. The number of complications was 1 in the percutaneous group and 6 in the open-surgery group. Whereas no adverse radiographic outcomes were found in the percutaneous group, the open-surgery group had 2 cases of inadequate reduction, 3 cases of joint remodelling, and 4 cases of intra-articular screw migration. The number of patients unable to return to their previous work activities was 1 (9%) in the percutaneous group and 3 (30%) in the open-surgery group. DISCUSSION: Arthroscopically assisted percutaneous screw fixation seems to ensure a simpler postoperative course, with fewer clinical and radiographic complications, as well as shorter tourniquet and immobilisation times. LEVEL OF EVIDENCE: IV, retrospective comparative study. PMID- 26993855 TI - Minimally invasive percutaneous plate osteosynthesis for distal radius fractures with long-segment metadiaphyseal comminution. AB - INTRODUCTION: Distal radius fractures with both metaphyseal and diaphyseal comminution are commonly encountered injuries due to high-energy trauma. However, effectively treating patients with this disease remains challenging for the surgeon. HYPOTHESIS: The goal of this study was to evaluate the outcomes of minimally invasive percutaneous plate osteosynthesis (MIPPO) technique for distal radius fractures with long-segment metadiaphyseal comminution. MATERIAL AND METHODS: Nine patients with distal radius fractures involving long-segment metadiaphyseal comminution were treated with MIPPO from June 2011 to May 2012. Radiograph index, the range of motion of the wrist and forearm, grip strength, the Disabilities of the Arm, Shoulder, and Hand (DASH) score were assessed at final follow-up. Additionally, time to bone healing, time to return to work or activity, and postoperative complications were also recorded. RESULTS: All nine fractures healed by 13+/-1.3 weeks postoperatively. At an average follow-up of 15.9+/-3.6 months, the radiographs revealed a mean radial inclination of 18.2+/ 2.7 degrees , a mean volar tilt of 10.7+/-3.2 degrees , and a radial shortening of 2.3+/-1.0mm. Nine patients had excellent wrist function according to the DASH score, range of motion, and grip strength. Except one patient experienced delayed healing of the distal incision, no complications occurred. All patients resumed work or activity within 16.2+/-1.9 weeks. DISCUSSION: Volar MIPPO is a safe and effective surgical treatment method for distal radius fractures with long-segment metadiaphyseal comminution, with few potential complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26993856 TI - Popliteal artery thrombosis complicating posterior tibial exostosis in a 35-year old male. AB - Chronic popliteal artery thrombosis complicating tibial exostosis has never been described as far as we know. Here, we report the case of a 35-year-old male patient complaining of intermittent claudication over the previous 4 months, without history of trauma or hereditary multiple exostoses. Clinical examination found no popliteal or distal pulses. The diagnosis was confirmed based on CT angiography showing distinct blockage of the contrast product over an exostosis on the posterior side of the proximal tibia. Treatment consisted of removing the exostosis and then bypassing the popliteal artery with a reversed autogenous venous graft. PMID- 26993857 TI - Bilateral fracture of the base of the middle phalanx in a climber: Literature review and a case report. AB - During climbing, tears of the annular pulley are the most common injuries, while fractures of the dorsal base of the middle phalanx are rare and atypical. Only a few cases have been reported in international literature. The authors present a case of a Salter-Harris type III fracture of the base of the middle phalanx of the middle finger in a young climber and a review of the literature. The patient was a 17-year-old boy who regularly and intensively practiced climbing. He consulted for a non-traumatic history of proximal pain of the interphalangeal joints of the middle fingers. On clinical examination, there was pain on the dorsal surface of the proximal interphalangeal joints, with no decrease in range of motion of the fingers. X-rays showed a Salter-Harris type III, displaced epiphyseal fracture of the dorsal base of the middle phalanx of the middle fingers. Conservative treatment resulted in fracture union and the patient had recovered normal activity of his hand at the 6-month follow-up. Stress fractures are common in athletes like climbers in response to repetitive and prolonged sports. Epiphyseal fractures are the most common injuries in young climbers. PMID- 26993858 TI - Novel interferonopathies associated with mutations in RIG-I like receptors. AB - Type I interferonopathies are a relatively new class of inherited autoimmune disorders associated with an inborn elevated interferon response. Activation of cytosolic receptors which recognize viral double stranded RNA including the RIG-I (retinoic acid-inducible gene I) like receptors RIG-I and MDA5 (melanoma differentiation-associated gene 5) has been shown to induce the transcription of type I interferon genes. Within recent years, with the help of next generation sequencing techniques in syndromic families, mutations in the genes encoding for RIG-I and MDA5 have been identified to cause rare diseases including Aicardi Goutieres syndrome, Systemic Lupus Erythematosus in certain individuals as well as classic and atypical Singleton-Merten syndrome. Patients carrying mono-allelic mutations in MDA5 and RIG-I show constitutive activation of the RIG-I receptors and downstream signalling associated with increased type I interferon production. Although differing in the degree of phenotypic expression and severity, the phenotype of these "novel" diseases shows a considerable overlap reflecting their common pathogenetic pathway. PMID- 26993861 TI - Primary venous insufficiency increases risk of deep vein thrombosis. AB - BACKGROUND: Varicose veins have been recognized as a risk factor for deep vein thrombosis (DVT). However, venous reflux has not carried the same correlation. This study evaluated the association between primary valvular reflux and DVT. METHODS: We performed a nested case-control study with enrollment of outpatients presenting to the vascular laboratory with signs and symptoms of DVT. All patients had a complete bilateral venous duplex examination evaluating for DVT and superficial and deep venous valvular reflux. Eighty-seven patients with confirmed DVT on venous duplex were selected for the study group. The control group was randomly selected from the same cohort in a 4:1 ratio matched by age and gender (n = 348). Groups were compared for the prevalence of deep and superficial reflux. RESULTS: DVT outpatients were 4.7-times more likely to have primary valvular reflux than symptomatic controls (65.5% vs 29.0%; 95% confidence interval [CI], 2.8-7.7; P < .000001). Deep reflux was 2.1-times more prevalent (36.8% vs 21.6%; odds ratio, 2.12; 95% CI, 1.28-3.51; P = .005) and superficial reflux was 4.6-times more prevalent (43.7% vs 14.4%; odds ratio, 4.62; 95% CI, 2.75-7.77; P < .0000001) in DVT patients than in controls. DVT patients were also 2.1-times more likely to have combined deep and superficial reflux than non-DVT patients (13.8% vs 6.6%, 95% CI, 1.08-4.75; P = .044). CONCLUSIONS: The prevalence of primary valvular reflux in patients with DVT is significantly higher than expected. Reflux may be considered as a novel risk factor for DVT. Two-thirds of patients with DVT have pre-existent primary chronic venous disease, which is likely to contribute to post-thrombotic morbidity. PMID- 26993860 TI - Validation of the Caprini risk assessment model for venous thromboembolism in high-risk surgical patients in the background of standard prophylaxis. AB - OBJECTIVE: We used the Caprini venous thromboembolism risk assessment score to prospectively evaluate if there was a correlation between the Caprini scores and the incidence of postoperative deep vein thrombosis (DVT) in high-risk surgical patients. A second objective was to determine whether patients at extremely high risk need a more effective prophylactic regimen. METHODS: This prospective multicenter observational study involved 140 high-risk patients who underwent abdominal (48%) or cranial and/or spinal (52%) surgery. All patients were assessed using the Caprini model and had a mean score of 9.5 +/- 2.7 (range, 5 15). Our standard prophylaxis for venous thromboembolism consisted of above-knee graduated compression stockings with 18 to 21 mm Hg pressure and subcutaneous low dose unfractionated heparin three times per day, starting on the first or second through the fifth postoperative day depending on the risk of bleeding. We performed a duplex ultrasound examination at baseline during the first 12 to 24 hours after surgery and then every 3 to 5 days until discharge to assess the lower limb venous system up to the inferior vena cava. The end point of the study was ultrasound verification of fresh DVT or pulmonary embolism (PE). Verification of PE was made in all cases of DVT using echocardiography, lung scintigraphy, combined single-photon emission computed tomography and X-ray computed tomography, or autopsy. RESULTS: Fresh postoperative DVT was found in 39 patients (28%). The incidence of DVT was 2% in patients with a Caprini score of 5 to 8, 26% in patients with scores of 9 to 11, and 65% in patients with scores of 12 to 15 (P for trend < .01). The risk for DVT was increased 18.7-fold for patients with scores of 9 to 11 and 98.4-fold for scores of 12 to 15 compared with patients with scores of 5 to 8. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.81-0.94) and a Caprini score of 11 was the cutoff point that provided the highest sensitivity combined with highest specificity. In the 77 patients with a score of <11, DVT occurred in 2 patients (3%). In contrast, in the 63 patients with a score of >= 11, DVT occurred in 37 patients (59%; P < .01). PE was found in 13 patients (9%) and confirmed with autopsy. In all cases, verified fresh DVT was the source of embolism. CONCLUSIONS: There was a significant correlation between Caprini scores and the incidence of postoperative DVT in high-risk surgical patients. A Caprini score of >= 11 can identify a subgroup of patients at extremely high risk. These patients need a more effective prophylactic regimen. PMID- 26993862 TI - Aspiration thrombectomy using a large-size catheter for acute lower extremity deep vein thrombosis. AB - OBJECTIVE: This study retrospectively evaluated the safety and efficacy of aspiration thrombectomy using a large-size catheter for acute lower extremity deep vein thrombosis (DVT). METHODS: All patients who underwent aspiration thrombectomy using 9F or 10F catheters for acute lower extremity DVT were included and analyzed. Aspiration thrombectomy was performed in all patients. Additional intravenous thrombolysis was performed in patients with residual thrombus, and stent placement was performed in patients with iliac vein compression syndrome. RESULTS: From October 2010 to September 2013, the study enrolled 68 patients (37 women, 31 men) with a mean age of 61.7 +/- 7.8 years (range, 24-86 years). All patients presented with lower extremity swelling and pain, and the duration of symptoms ranged from 1 to 14 days. The DVTs involved popliteal-iliofemoral veins in 29 patients, iliofemoral veins in 31, and iliac veins in 8. Endovascular procedures were performed in all patients with a technical success rate of 100%. Aspiration alone was effective in 47 patients, and additional thrombolysis was required in the remaining 21. An additional stent was required in 32 patients. Significant improvement in presenting symptoms was achieved in all patients after the procedures, with a clinical success rate of 100%. There were no procedure-related or thrombolysis-related complications. The Villalta scores were <5 in 60 patients and from 5 to 9 in four patients. Primary and secondary patency rates were 89.1% (57 of 64) and 96.9% (62 of 64) at 1 year of follow-up. CONCLUSIONS: Aspiration thrombectomy using a large-size catheter is safe and effective for acute lower extremity DVT. PMID- 26993864 TI - Discussion. PMID- 26993863 TI - The prevalence of and predictors to indicate bilateral venous duplex ultrasound testing to detect contralateral asymptomatic lower extremity deep venous thrombosis in patients with acute symptomatic lower extremity deep venous thrombosis. AB - OBJECTIVE: The goal of this study was to determine the prevalence of and predictors to indicate bilateral venous duplex ultrasound (DU) to detect contralateral asymptomatic deep venous thrombosis (DVT) in patients with acute symptomatic lower extremity DVT. METHODS: Venous DU reports along with medical records of the patients were collected from February 2005 to April 2012 in a tertiary university hospital in Botucatu, Brazil. All patients with DVT detected in one lower extremity routinely underwent contralateral limb venous DU examination. Exclusion criteria were previous DVT in the contralateral asymptomatic limb, thrombophlebitis, workup for pulmonary embolism, and bilateral symptomatic lower extremities. RESULTS: Scans were done in 579 patients to rule out contralateral lower extremity DVT whenever DVT was confirmed in the ipsilateral lower extremity; of these, 108 patients (18.6%) had an abnormal finding on DU examination for DVT in the contralateral limb, which was proximal DVT in 71.5%. Age >60 years (odds ratio [OR], 3.33; 95% confidence interval [CI], 1.447-7.670), malignant disease (OR, 5.21; 95% CI, 1.943-14.015), and the association of trauma plus malignant disease (OR, 7.11; 95% CI, 1.640-30.863) were the main predictors. CONCLUSIONS: Age >60 years, malignant disease, lower extremity trauma, inpatient status, and recent hospitalization are risk factors associated with a high incidence of asymptomatic contralateral lower extremity DVT in patients with ipsilateral lower extremity DVT. Therefore, we recommend routine performance of a venous DU examination on the contralateral lower extremity whenever these risk factors are present in patients with ipsilateral lower extremity DVT. PMID- 26993859 TI - Effects of glucagon-like peptide-1 on the differentiation and metabolism of human adipocytes. AB - BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP-1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up-regulated in AT of insulin-resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP-1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects. EXPERIMENTAL APPROACH: We analysed the effects of GLP-1 on human AT and isolated adipocytes in vitro and the effects of GLP-1 mimetics on AT of morbidly obese T2D subjects in vivo. KEY RESULTS: GLP-1 down-regulated the expression of lipogenic genes when administered during in vitro differentiation of human adipocytes from morbidly obese patients. GLP-1 also decreased the expression of adipogenic/lipogenic genes in AT explants and mature adipocytes, while increasing that of lipolytic markers and adiponectin. In 3T3-L1 adipocytes, GLP-1 decreased free cytosolic Ca2+ concentration ([Ca2+]i). GLP-1-induced responses were only partially blocked by GLP-1 receptor antagonist exendin (9-39). Moreover, administration of exenatide or liraglutide reduced adipogenic and inflammatory marker mRNA in AT of T2D obese subjects. CONCLUSIONS AND IMPLICATIONS: Our data suggest that the beneficial effects of GLP-1 are associated with changes in the adipogenic potential and ability of AT to expand, via activation of the canonical GLP-1 receptor and an additional, as yet unknown, receptor. PMID- 26993865 TI - Quantifying saphenous recirculation in patients with primary lower extremity venous reflux. AB - BACKGROUND: The great saphenous vein (GSV) in patients with superficial venous insufficiency might act as a beneficial conduit for antegrade venous drainage and also as a harmful conduit for promotion of reflux and/or recirculation and subsequent skin changes. The aim of this study was to measure the antegrade and retrograde GSV volume displacements during calf compression and release maneuvers. This was used to quantify harm over benefit with a recirculation index (RCI). METHODS: Sixteen legs (nine right) from 16 patients (nine male) with primary superficial venous insufficiency were scanned standing with duplex ultrasound, at the upper thigh GSV, 10 cm below the sapheno-femoral junction. The clinical, etiological, anatomical, pathophysiological class was C2 = 3, C3 = 2, C4a = 6, C4b = 4, C5 = 1. The median age (range), venous clinical severity score, and refluxing GSV diameter were 63 (21-79) years, 8 (4-16), and 7 (5-10) mm, respectively. A manual calf compression and release (MCCR) maneuver was performed once, and a cyclical calf compression and release (CCCR) three times for repeatability. With the CCCR maneuver, the calf-cuff and inflation-deflation pump provided a cyclical compression pressure of 120 mm Hg (3 seconds) with a release time of 16.4 seconds to standardize venous refilling time. RESULTS: The results are expressed as median [interquartile range]. The CCCR compared with the MCCR resulted in longer reflux duration (16.4 [8.2-16.4] seconds vs 5.7 [3.7-6.8] seconds; P < .0005), higher time-averaged mean velocities in reflux (23.5 [14.9 27.9] cm/s vs 14.1 [9-17.6] cm/s; P < .0005) and greater reflux volume displacements (81.7 [38.8-152.8] mL vs 27.3 [16.4-53.4] mL; P < .0005). There were significant correlations between increasing antegrade volume measurements and increasing reflux volume measurements irrespective of whether CCCR, (r = 0.841; P < .0005) or MCCR (r = 0.762; P = .001) was used. This implies that the displaced antegrade volume might have a causal effect on the resulting reflux volume. The ratio of reflux volume/antegrade volume (RCI) was 2.14 [1.58-2.74] with the CCCR. This supports the recirculation phenomenon. Adjusted to a standard median for each leg, the repeatability limits (three times) of the RCI was excellent at 2.14 (95% confidence interval, 2.09-2.21). CONCLUSIONS: In this study we measured the behavior of the GSV in terms of harmful reflux over beneficial drainage using the RCI. We recognize that reflux values depend on the type of provocation test and the amount of displaced antegrade volume. This limitation might be overcome by factoring reflux as an expression of antegrade flow using the RCI. When standardized, a test for quantifying saphenous recirculation might have many clinical applications. The next step should be a prospective study to validate the RCI with clinical and quality of life parameters. PMID- 26993866 TI - Transjugular liver access cannula as a guiding instrument for the recanalization of chronic venous occlusions. AB - BACKGROUND: Chronic venous occlusions can result in debilitating symptoms and can be refractory to standard methods of venous recanalization because of the formation of dense fibrous tissue. A transjugular liver access cannula can be incorporated into recanalization efforts to treat such refractory cases. This report describes our experience using the transjugular liver access cannula technique in nine patients. METHODS: A review of patients requiring venous recanalization between May 2012 and October 2014 identified nine cases that required the use of a transjugular liver access cannula as a guiding instrument. Lesion characteristics, technical success, and clinical outcomes were evaluated. RESULTS: The transjugular liver access cannula was used to traverse a total of nine chronic occlusions in both the upper and lower central venous systems in nine patients. The technical success rate was 100%. There were no clinically significant complications. One patient was lost to follow-up. Of the remaining eight patients, seven experienced symptomatic relief within 1 month of recanalization. CONCLUSIONS: The transjugular liver access cannula may serve as a useful adjunctive tool during difficult venous recanalizations, especially when traditional guidewire and catheter techniques fail. PMID- 26993867 TI - Stent migration after endovascular stenting in patients with nutcracker syndrome. AB - OBJECTIVE: In this study, we sought to investigate the incidence of stent migration after endovascular stenting (EVS) in patients with nutcracker syndrome (NCS) and to discuss the related factors. METHODS: We retrospectively evaluated the data of all patients with NCS who were treated by EVS at our single center between January 2004 and October 2014. Data collection included details on clinical findings, radiologic evaluation, laboratory values, EVS procedure, stent size, and morbidity of stent migration. Sex, size of stents, interval (between EVS and stent migration), and preoperative parameters of the left renal vein (LRV) on duplex ultrasound (anteroposterior diameter in aortomesenteric portion and renal hilum of LRV, peak velocity in aortomesenteric portion and renal hilum of LRV) were analyzed. RESULTS: A total of 75 patients (49 men) with a median age of 27 years (range, 16-43 years) underwent EVS for NCS. During a mean 55 months (range, 6-126 months) of follow-up, stent migration occurred in five patients (6.7%), and all of them were male. The stent migrated into the right ventricle in one patient, right atrium in one patient, inferior vena cava in two patients, and left side of the LRV in one patient. There were no significant differences in preoperative anteroposterior diameter and peak velocity of the aortomesenteric portion and renal hilum of the LRV on duplex ultrasound between patients with and without stent migration. There were also no significant differences in these parameters between patients with deployment of 12-mm and 14-mm-diameter stents. CONCLUSIONS: Stent migration after EVS in patients with NCS is not as rare as we originally thought. Preoperative anatomic parameters of the LRV need to be more accurately measured. Stent choice for the individual patient and accurate stent deployment are important to avoid stent migration. Closer follow-up and early detection and treatment can reduce the number of stent migrations into the heart. PMID- 26993868 TI - Risk factors for infectious and noninfectious complications of totally implantable venous catheters in cancer patients. AB - OBJECTIVE: The aim of this study was to investigate the risk factors for complications of totally implantable catheters in a referral cancer center. METHODS: This was a retrospective study of prospectively collected data of all consecutive cancer patients undergoing port placement, with a primary outcome of interest of major complication and subanalysis of the types of complications. RESULTS: We studied 1255 nonvalved implanted port catheters inserted in 1230 patients, for a combined total of 469,882 catheter-days of use. Venous puncture was ultrasound (US)-guided in 1049 cases (84%). Inadvertent arterial puncture occurred in 14 cases (1.1%) and was more frequent in procedures not guided by US (P = .045). Among the outpatients, 90 (9%) developed infection, and 75 (29%) of the hospitalized patients (P < .001) developed infections. Infection was diagnosed in 131 catheters (13%) implanted through the internal jugular vein (IJV), 23 catheters (14%) implanted in the subclavian vein (SCV), 1 catheter (5%) implanted in the external jugular vein, and 10 catheters (31%) implanted in the femoral vein (P = .044). In the multivariate analysis, only the hospitalization regimen maintained statistical significance, with hospitalization presenting as a risk factor for infection (P < .001). Regarding the introduction site, ambulatory patients in whom the femoral vein was the site of access had more infections than the others (28.6% vs 9.4% of the IJV, 4.8% of the SCV, and 4.8% of the external jugular vein; P = .019), which did not occur among the hospitalized patients (33.3% vs 26.5% of IJV and 39.5% of the SCV; P = .218). CONCLUSIONS: Not using US is a risk factor for iatrogenic arterial puncture. Port implantation in hospitalized patients and the use of femoral access are risk factors for infection. PMID- 26993869 TI - The comparative hemodynamic efficacy of lower limb muscles using transcutaneous electrical stimulation. AB - BACKGROUND: Circulation in the limbs can be augmented using transcutaneous electrical stimulation devices. The optimum muscle stimulation sites for enhancement of vascular hemodynamic parameters have not been identified. METHODS: Seven suitable anatomic sites were identified within the right leg. Twelve healthy participants were recruited (mean age, 23.1 +/- 3 years; body mass index, 23.1 +/- 3 kg/m(2)). Muscles were stimulated by transcutaneous bipolar electrodes at a current twice their motor threshold, at 1 Hz, for 5 minutes. Hemodynamic ultrasound measurements were taken from the right femoral vein. Laser Doppler measurements from the feet of the stimulated and nonstimulated sides were obtained. Baseline measurements were compared with readings after 5 minutes of stimulation, with device active. Discomfort experienced for stimulation of each muscle was rated out of 100. RESULTS: Hemodynamic changes displayed large intersubject variation, with no muscle statistically superior to the others. All muscles increased peak velocity; contraction of medial gastrocnemius increased time-averaged maximum velocity and volume flow. All muscles increased foot fluximetry (P < .05). Discomfort correlated weakly with current applied. Tibialis anterior and vastus lateralis were most tenable. CONCLUSIONS: Transcutaneous stimulation increases hemodynamic parameters significantly, locally and systemically. No optimum stimulation site has been identified, and it is limited by comfort and variability in the subject's response. Gastrocnemius, tibialis anterior, and vastus lateralis all provoke large changes in hemodynamic parameters, but clinical efficacy in disease prevention and management has not been explored. PMID- 26993870 TI - Lymph proteins may access peripheral blood without entering thoracic duct in patients with lymphatic dysfunction. AB - OBJECTIVE: The objective was to investigate the hypothesis that lymphovenous communications, which allow lymph proteins to access peripheral blood without first entering the thoracic duct, open in patients with abnormal lymphatic function. METHODS: Routine lymphoscintigraphy of 182 patients, including 27 without clinical evidence of lymphedema (controls), was performed immediately and 45 and 150 minutes after subcutaneous injection of technetium Tc 99m nanocolloid into both feet. Counts per pixel in a region of interest over the liver (L) were divided by total counts in bilateral ilioinguinal nodes (N) at 45 minutes (L/N45) and 150 minutes (L/N150). If all activity leaving ilioinguinal lymph nodes entered the thoracic duct, these L/N ratios would be similar from patient to patient. RESULTS: Eight patients were excluded because of immediate liver activity suggesting inadvertent intravascular injection of tracer. In controls (group 1), L/N150 displayed a normal distribution with mean (+/- standard deviation) of 0.16 (0.09) * 10(-4) pixels(-1). Patients with L/N150 >0.34 * 10( 4) pixels(-1) (ie, 0.16 + 2 standard deviations) were assumed to have lymphovenous communications. Of 34 patients with clinical evidence of lymphedema but with normal findings on lymphoscintigraphy (group 2), 3 (9%) had lymphovenous communications; of 114 with abnormalities on lymphoscintigraphy (group 3), 43 (38%) had lymphovenous communications (P = .001). N45/150 was significantly higher than L45/150 in all four groups, indicating arrival of activity in nodes before the liver. Abnormal features of lymphoscintigraphy-lymph transport delay, popliteal node visualization, and diversion of lymph through the skin-showed no association with L/N ratios. CONCLUSIONS: Lymphovenous communications exist in about one-third of patients with abnormalities detected on lymphoscintigraphy. The timings of tracer arrival in the liver and lymph nodes is consistent with lymphovenous communication within lymph nodes themselves. PMID- 26993871 TI - 1D-1H-nuclear magnetic resonance metabolomics reveals age-related changes in metabolites associated with experimental venous thrombosis. AB - OBJECTIVE: Age is a significant risk factor for the development of venous thrombosis (VT), but the mechanism(s) that underlie this risk remain(s) undefined and poorly understood. Aging is known to adversely influence inflammation and affect metabolism. Untargeted metabolomics permits an agnostic assessment of the physiological landscape and lends insight into the mechanistic underpinnings of clinical phenotypes. The objective of this exploratory study was to test the feasibility of a metabolomics approach for identifying potential metabolic mechanisms of age-related VT. METHODS: We subjected whole blood samples collected from young and old nonthrombosed controls and VT mice 2 days after thrombus induction using the electrolytic inferior vena cava, to a methanol:chloroform extraction and assayed the resulting aqueous fractions using 1D-(1)H- nuclear magnetic resonance. Normalized mouse metabolite data were compared across groups using analysis of variance (ANOVA) with Holm-Sidak post-testing. In addition, associations between metabolite concentrations and parameters of thrombosis such as thrombus and vein wall weights, and markers of inflammation, vein wall P- and E-selectin levels, were assessed using linear regression. The relatedness of the found significant metabolites was visually assessed using a bioinformatics tool, Metscape, which generates compound-reaction-enzyme-gene networks to aid in the interpretation of metabolomics data. RESULTS: Old mice with VT had a greater mean vein wall weight compared with young mice with VT (P < .05). Clot weight differences between old and young mice followed the same trend as vein wall weight (0.011 +/- 0.04 g vs 0.008 +/- 0.003 g; P = not significant). Glutamine (ANOVA, P < .01), proline (ANOVA, P < .01), and phenylalanine (ANOVA, P < .05) levels were increased in old VT mice compared with age-matched controls and young VT mice. Betaine and/or trimethylamine N-oxide levels were increased in aged mice compared with young animals. Vein wall weight was strongly associated with glutamine (P < .05), and phenylalanine (P < .01) concentrations and there was a trend toward an association with proline (P = .09) concentration. Vein wall P selectin, but not E-selectin levels, were increased in old VT mice and were associated with the three found metabolites of age-related VT. Collectively, with the addition of glutamate, these metabolites form a single compound-reaction enzyme-gene network that was generated by Metscape. CONCLUSIONS: We used 1D-(1)H nuclear magnetic resonance-metabolite profiling to identify, for the first time, in an experimental model, three potential metabolites, glutamine, phenylalanine, and proline, associated with age-related VT. These metabolites are metabolically related and their levels are associated with vein wall weight and P-selectin concentrations. In aggregate, these findings provide a "roadmap" of pathways that could be interrogated in future studies, which could include provocation of the glutamine, phenylalanine, and proline pathways in the vein wall. This study introduces metabolomics as a new approach to furthering knowledge about the mechanisms of age-related VT. PMID- 26993873 TI - Aneurysm of the aberrant right thoracic duct. PMID- 26993872 TI - Nutcracker syndrome and deep venous thrombosis in a patient with duplicated inferior vena cava. AB - Duplicated inferior vena cava is a rare anomaly, and thrombosis in one or both segments is even less frequent. We present a case of deep venous thrombosis of the left lower limb involving the popliteal, femoral, and iliac veins as well as the left segment of the duplicated vena cava and nutcracker syndrome. After catheter-directed thrombolysis complemented by mechanical thrombolysis, the compromised veins had complete revascularization; the nutcracker syndrome was treated with stent placement, followed by the use of anticoagulants. There was technical success and complete recovery of the patient. PMID- 26993874 TI - Current concepts in repair of extremity venous injury. AB - OBJECTIVE: Extremity venous injury management remains controversial. The purpose of this communication is to offer perspective as well as experiential and technical insight into extremity venous injury repair. METHODS: Available literature is reviewed and discussed. Historical context is provided. Indication, the decision process for repair, including technical conduct, is delineated. In particular, the authors' experiences in both civilian and wartime injury are used for perspective. RESULTS: Extremity venous injury repair was championed within data from the Vietnam Vascular Registry. However, patterns of extremity venous injury differ between combat and civilian settings. Since Vietnam, civilian descriptive series opine the benefits and potential complications associated with both venous injury repair and ligation. These surround extremity edema, chronic venous insufficiency, thromboembolism, and limb loss. Whereas no clear superiority in either approach has been identified to date, there appears to be no increased risk of pulmonary embolism or chronic venous changes with repair. Newer data from the wars in Iraq and Afghanistan and meta-analysis have reinforced this and also have suggested limb salvage benefit for extremity venous repair in combined arterial and venous injuries in modern settings. The patient's physiologic state and associated injury drive five triage categories suggesting vein injury management. Vein repair thrombosis occurs in a significant proportion, yet many recanalize and possibly have a positive impact on limb venous return. Further, early decompression favors reduced blood loss, acute edema, and inflammation, supporting collateral development. Large soft tissue injury minimizing collateral capacity increases the importance of repair. Constructs of repair are varied with modest differences in patency. Venous shunting is feasible, but specific roles remain nebulous. CONCLUSIONS: An aggressive posture toward extremity venous injury repair seems justified today because of the likely role in reducing venous hypertensive sequelae as well as a potential role in limb salvage. Appropriate triage selection for extremity vein repair is essential. PMID- 26993875 TI - The efficacy of intermittent pneumatic compression in the prevention of lower extremity deep venous thrombosis. AB - Intermittent pneumatic compression (IPC) has been used to prevent lower extremity deep venous thrombosis for more than 30 years and is a popular choice for prophylaxis among both physicians and patients because of its efficacy and reduced risk of bleeding compared with pharmacologic prophylaxis. However, the efficacy of IPC may depend on the clinical situation as well as on several variables associated with the devices. To determine the efficacy of IPC, recent guidelines and literature were reviewed. IPC is efficacious as a sole prophylactic agent in low- or moderate-risk surgical patients and in patients with high risk of bleeding with pharmacologic prophylaxis. In high-risk surgical and medical patients, IPC is recommended as a synergistic tool in combination with pharmacologic agents, if pharmacologic agents are not contraindicated. No specific compression modality proved its superiority, although newer portable battery-powered devices seem to allow better patient compliance and satisfaction. PMID- 26993876 TI - Evaluation and management of peripheral venous and lymphatic malformations. AB - The International Society for Study of Vascular Anomalies (ISSVA) broadly categorizes vascular anomalies as vascular tumors or vascular malformations. The latter are congenital lesions that are further categorized by their flow properties and include high-flow arteriovenous malformations, slow-flow venous and lymphatic malformations, and congenital mixed syndromes, which can include a combination of malformations. Unlike vascular tumors, vascular malformations never regress and can persist and grow for the duration of the patient's lifespan. As our understanding of the natural history, hemodynamics, and treatment outcomes of these lesions has expanded and evolved over the last few decades, certain fundamental diagnostic and therapeutic principles have been established and are considered standard of care. These overarching principles are crucial to adhere to in the overall management of these lesions and are highlighted and expanded on in this report, which focuses exclusively on peripheral slow-flow venous and lymphatic malformations. PMID- 26993877 TI - Quantitation of fetal DNA fraction in maternal plasma using circulating single molecule amplification and re-sequencing technology (cSMART). AB - BACKGROUND: Calculation of the fetal DNA fraction (FF) is important for reliable and accurate noninvasive prenatal testing (NIPT) for fetal genetic abnormalities. The aim of the study was to develop and validate a novel method for FF determination. METHODS: FF was calculated using the chromosome Y (ChrY) sequence read assay and by circulating single molecule amplification and re-sequencing technology of 76 autosomal SNPs. RESULTS: By Pearson correlation for FF (4.73 22.11%) in 33 male pregnancy samples, the R(2) co-efficient for the 76-SNP versus the ChrY assay was 0.9572 (p<0.001). In addition, the co-efficient of variation (CV) of FF measurement by the 76-SNP assay was low (0.15-0.35). As a control, the FF measurement for four non-pregnant plasma samples was virtually zero. In prospective longitudinal studies of 14 women with normal pregnancies, FF generally increased with gestational age. However, in eight women (71%) there was a significant decrease in FF between the first trimester (11-13 weeks) and the second trimester (15-19 weeks), and this was attributable to significant maternal weight gain. CONCLUSIONS: The novel 76-SNP cSMART assay has the precision to accurately measure FF in all pregnancies at a detection threshold of 5%. Based on FF trends in individual pregnancies, our results suggest that the end of the first trimester may be a more optimal window for performing NIPT. PMID- 26993878 TI - Techno-functional and nutritional performance of commercial breads available in Europe. AB - In recent years, the growing interest for well-being and healthy lifestyle together with an increasing awareness of the close relationship between food and health have boosted the production of an increasing number of novel goods to be placed in both gluten-containing and gluten-free products market. The objective of this study was to provide a realistic and detailed overview of the current bread-market supply in order to evaluate the overall quality of the available offer in this prioritized food industry area. Twenty commercial breads consisting of gluten (n = 10) and gluten-free (n = 10) samples currently available in the European market have been assessed by physical-chemical, technological, nutritional, and sensory determinations. The quality parameters obtained were related to each other by using Pearson correlations, while sample classification was achieved by applying factor analysis. Higher values for protein and bio accessible polyphenols content, aroma and taste quality, and low and moderate expected glycaemic index corresponded to gluten containing breads. Although the main distinction was between gluten and gluten-free samples as it was expected, classification of breads allowed differentiating samples with different formulations in terms of presence/absence of alternative, innovative, and nutrient-dense raw materials. PMID- 26993879 TI - Comment on: different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis: reply. PMID- 26993880 TI - Microcephaly and Zika virus infection. PMID- 26993881 TI - Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial. AB - BACKGROUND: The excruciating pain of patients with renal colic on presentation to the emergency department requires effective analgesia to be administered in the shortest possible time. Trials comparing intramuscular non-steroidal anti inflammatory drugs with intravenous opioids or paracetamol have been inconclusive because of the challenges associated with concealment of randomisation, small sample size, differences in outcome measures, and inadequate masking of participants and assessors. We did this trial to develop definitive evidence regarding the choice of initial analgesia and route of administration in participants presenting with renal colic to the emergency department. METHODS: In this three-treatment group, double-blind, randomised controlled trial, adult participants (aged 18-65 years) presenting to the emergency department of an academic, tertiary care hospital in Qatar, with moderate to severe renal colic (Numerical pain Rating Scale >= 4) were recruited. With the use of computer generated block randomisation (block sizes of six and nine), participants were assigned (1:1:1) to receive diclofenac (75 mg/3 mL intramuscular), morphine (0.1 mg/kg intravenous), or paracetamol (1 g/100 mL intravenous). Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants achieving at least a 50% reduction in initial pain score at 30 min after analgesia, assessed by intention-to-treat analysis and per-protocol analysis, which included patients where a calculus in the urinary tract was detected with imaging. This trial is registered with ClinicalTrials.gov, number NCT02187614. FINDINGS: Between Aug 5, 2014, and March 15, 2015, we randomly assigned 1645 participants, of whom 1644 were included in the intention-to-treat analysis (547 in the diclofenac group, 548 in the paracetemol group, and 549 in the morphine group). Ureteric calculi were detected in 1316 patients, who were analysed as the per-protocol population (438 in the diclofenac group, 435 in the paracetemol group, and 443 in the morphine group). The primary outcome was achieved in 371 (68%) patients in the diclofenac group, 364 (66%) in the paracetamol group, and 335 (61%) in the morphine group in the intention-to-treat population. Compared to morphine, diclofenac was significantly more effective in achieving the primary outcome (odds ratio [OR] 1.35, 95% CI 1.05-1.73, p=0.0187), whereas no difference was detected in the effectiveness of morphine compared with intravenous paracetamol (1.26, 0.99-1.62, p=0.0629). In the per-protocol population, diclofenac (OR 1.49, 95% CI 1.13-1.97, p=0.0046) and paracetamol (1.40, 1.06-1.85, p=0.0166) were more effective than morphine in achieving the primary outcome. Acute adverse events in the morphine group occurred in 19 (3%) participants. Significantly lower numbers of adverse events were recorded in the diclofenac group (7 [1%] participants, OR 0.31, 95% CI 0.12 0.78, p=0.0088) and paracetamol group (7 [1%] participants, 0.36, 0.15-0.87, p=0.0175) than in the morphine group. During the 2 week follow-up, no additional adverse events were noted in any group. INTERPRETATION: Intramuscular non steroidal anti-inflammatory drugs offer the most effective sustained analgesia for renal colic in the emergency department and seem to have fewer side-effects. FUNDING: Hamad Medical Corporation Medical Research Center, Doha, Qatar. PMID- 26993882 TI - Non-steroidal anti-inflammatory drugs for renal colic. PMID- 26993883 TI - Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. AB - BACKGROUND: The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly. On Feb 1, 2016, WHO declared the suspected link between Zika virus and microcephaly to be a Public Health Emergency of International Concern. This association, however, has not been precisely quantified. METHODS: We retrospectively analysed data from a Zika virus outbreak in French Polynesia, which was the largest documented outbreak before that in the Americas. We used serological and surveillance data to estimate the probability of infection with Zika virus for each week of the epidemic and searched medical records to identify all cases of microcephaly from September, 2013, to July, 2015. Simple models were used to assess periods of risk in pregnancy when Zika virus might increase the risk of microcephaly and estimate the associated risk. FINDINGS: The Zika virus outbreak began in October, 2013, and ended in April, 2014, and 66% (95% CI 62-70) of the general population were infected. Of the eight microcephaly cases identified during the 23-month study period, seven (88%) occurred in the 4-month period March 1 to July 10, 2014. The timing of these cases was best explained by a period of risk in the first trimester of pregnancy. In this model, the baseline prevalence of microcephaly was two cases (95% CI 0-8) per 10,000 neonates, and the risk of microcephaly associated with Zika virus infection was 95 cases (34-191) per 10,000 women infected in the first trimester. We could not rule out an increased risk of microcephaly from infection in other trimesters, but models that excluded the first trimester were not supported by the data. INTERPRETATION: Our findings provide a quantitative estimate of the risk of microcephaly in fetuses and neonates whose mothers are infected with Zika virus. FUNDING: Labex-IBEID, NIH MIDAS, AXA Research fund, EU-PREDEMICS. PMID- 26993885 TI - Journal of Vascular Surgery: Venous and Lymphatic Disorders SVS and AVF Presidents' perspective. PMID- 26993884 TI - Journal of Vascular Surgery: Venous and Lymphatic Disorders Editors' perspective. PMID- 26993886 TI - Post-thrombotic syndrome 3 years after deep venous thrombosis in the Thrombosis and Pulmonary Embolism in Out-Patients (TULIPA) PLUS Registry. AB - BACKGROUND: Reported post-thrombotic syndrome (PTS) rates may be confounded by including patients with a history of deep venous thrombosis (DVT) before the index event, varicose veins, or chronic venous insufficiency independent of PTS. We were interested in assessing PTS incidence rates of patients without these pre existing disease conditions. METHODS: A prospective registry with a 3-year follow up after an initial DVT was assessed. Available for analysis were 135 ambulatory patients without a history of DVT (before the index DVT), signs of varicose veins, or chronic venous insufficiency affecting the ipsilateral or contralateral leg, and Villalta score. RESULTS: PTS was detected in 24.5% of patients, with 17.0% having mild (Villalta score, 5-9), 6.0% moderate (score, 10-14), and 1.5% severe PTS (score >=15) after a first DVT. Of these, 52.6% had proximal and 47.4% distal DVT; 63.7% were provoked and 35.6% unprovoked (one patient missing). Patients with proximal DVT (32.4%) significantly more often developed any PTS compared with patients with distal DVT (15.6%; P = .024); however, groups were similar with regard to severity of PTS by the four-level Villalta score (P = .109). In univariate analysis, PTS was more frequent (odds ratio, 95% confidence interval) with higher age (1.06 per year; 1.02-1.09), a body mass index of 25 to 30 kg/m(2) (2.38; 0.71-7.97) and >=30 kg/m(2) (6.08; 1.75-21.14), proximal vs distal DVT (2.59; 1.12-5.98), and calf swelling >=3 cm larger than the asymptomatic leg (3.77; 1.66-8.55). In a multivariate analysis, age (1.05; 1.01 1.09) and calf swelling >=3 cm larger than the asymptomatic leg (2.94; 1.20-7.20) remained predictive for PTS. Compression therapy was used by 78.5% of patients at the 1-year follow-up and by 46.7% at the 3-year follow-up. Both rates were higher in patients with PTS (93.9%) vs no PTS (66.7%). CONCLUSIONS: This prospective survey demonstrates a low rate of PTS in patients with a first DVT and no pre existing DVT, varicose veins, or chronic venous insufficiency, and a high adherence rate to compression therapy, within the first 3 years of follow-up. Age and marked calf swelling were independent predictors of PTS. PMID- 26993887 TI - Prospective, randomized, controlled trial comparing the effectiveness of adjustable compression Velcro wraps versus inelastic multicomponent compression bandages in the initial treatment of leg lymphedema. AB - BACKGROUND: Inelastic multicomponent compression (ICM) bandages applied by specialized medical staff are the standard of care for compression therapy of lymphedema of the extremities. However, new adjustable compression wraps (ACWs), which can be applied by patients themselves and, up to now, have been mainly recommended for the maintenance treatment phase of lymphedema, may be an important step toward the self-management of the initial treatment phase. METHODS: This prospective, randomized, controlled comparative study assessed the effectiveness of an ACW in the treatment of leg lymphedema, compared with the traditional treatment with conventional IMC bandages. Included were 30 hospitalized patients admitted due to moderate to severe unilateral lymphedema (stages 2-3) of the leg. The primary outcome measures in both groups were reduction in volume of the affected leg and interface pressure after 2 and 24 hours. Patients were randomized into two groups of 15 patients: group A received ACW and group B received IMC bandages, both applied by experienced staff. After 2 hours, the staff replaced IMC bandages and the patients applied ACW, as previously instructed. Finally, compression was removed after 24 hours. Classic water displacement volumetry was performed before compression and after 2 hours and after 24 hours of compression. The interface pressure was measured immediately after application of compression, 2 hours after compression, before and after compression renewal, and finally, after 24 hours. Patients in the ACW group were allowed to adjust the wrap themselves when they considered it necessary. RESULTS: The reduction in median volume after 2 hours was 109 mL (interquartile range [IQR], 64-271 mL; -3.1%) in the ACW group and 75 mL (IQR, 41 135; -2.4%) in the IMC group (not significant). After 24 hours, the reduction in median volume was 339 mL (IQR, 231-493 mL; -10.3%) in the ACW group and 190 mL (IQR, 113-296 mL; -5.9%) in the IMC group (P < .05). The interface pressure dropped significantly after 2 and 24 hours in the IMC group (-50% and -6%), but significantly less in the ACW group (-26% and -44%), mainly due to self readjustment. The median pressures achieved after self-application of ACW (52 mm Hg; IQR, 44-61 mm Hg) were of the same order as those produced by the nurses after the first application of ACW (53 mm Hg; IQR, 39-59 mm Hg), with less variation. CONCLUSIONS: In patients with moderate to severe lymphedema of the legs, ACW achieved a significantly more pronounced reduction in volume after 24 hours than IMC bandages. Patients were able to apply and adjust the device after being instructed in its use and after an initial 2-hour period of wear. Autonomous handling of ACW seemed to improve the clinical outcome and is a promising step toward self-management involving effective compression. PMID- 26993888 TI - Six-year follow-up of endovenous laser ablation for great saphenous vein incompetence. AB - OBJECTIVE: Treatment of chronic venous insufficiency of the great saphenous veins by endovenous laser ablation yields good short- and medium-term results, as assessed clinically and technically by echo-color-Doppler. At present, scarce data are available on the long-term results of endovenous laser ablation. We wanted to assess the long-term efficacy of endovenous laser ablation. METHODS: We performed a prospective 6-year follow-up cohort study, with recruitment between 2003 and 2004, and the follow-up completed in 2010. The setting was an ambulatory care/day surgery. Of 209 consecutive patients who underwent endovenous laser ablation at our institution during the recruitment period, five (2.4%) did not complete the procedure due to technical reasons. Of 204 patients who successfully completed the intervention, 14 (6.8%) were lost for follow-up, and 190 completed the planned 6-year follow-up. The intervention was an endovenous laser ablation using a 980-nm laser diode. Clinical and echo-color-Doppler evaluations were regularly scheduled for all patients during the planned follow-up period. The incidence of clinical and echo-color-Doppler confirmed endovenous laser ablation failures over a 6-year follow-up period. Potential associations between failures and patients' characteristics, echo-color-Doppler findings, or surgical features were also investigated. RESULTS: Symptomatic clinical endovenous laser ablation failures occurred in 22 (11.6%; 95% confidence interval [CI], 7.4-17.0%) patients; while 57 (30.0%; 95% CI, 23.6-37.1%) had echo-color-Doppler-confirmed failures. Only two patients (1.1%; 95% CI, 0.1%-3.8%) had both symptomatic clinical and echo-color-Doppler-confirmed failures. Three features of the great saphenous vein: an "atypical" junction, a junction diameter >=8 mm, and a mean trunk diameter >=8 mm, were independently associated with echo-color-Doppler confirmed failures on multivariate logistic regression analysis. CONCLUSIONS: Six years after endovenous laser ablation, most patients were improved on clinical grounds, and more than two-thirds had no saphenous insufficiency at echo-color Doppler. Only a minority had both clinical and echo-color-Doppler-confirmed failures. Anatomical features of the junction and the saphenous diameter both at the junction and at the trunk independently predicted echo-color-Doppler confirmed failures. PMID- 26993889 TI - Invited commentary. PMID- 26993890 TI - Analysis of venous thromboembolic events after saphenous ablation. AB - BACKGROUND: Venous thromboembolic events after saphenous vein ablation procedures for varicose veins have been reported. Current knowledge of these events is based on single-institution studies or studies with small numbers of patients. METHODS: The National Surgical Quality Improvement Program (NSQIP) database (2005-2009) was used to identify 3874 patients who underwent radiofrequency ablation (RFA) or endovenous laser ablation (EVLA) of the saphenous veins with or without stab phlebectomy. Outcome variables included documented postoperative deep vein thrombosis (DVT) or pulmonary embolism (PE). Bivariate and multivariate logistic regression analyses were performed to identify factors associated with venous thromboembolic events after ablation procedures. RESULTS: Procedures for lower extremity varicose veins included RFA in 2897 patients (74.8%) and EVLA in 977 (25.2%). Patients who underwent RFA were more likely to be older, obese, diabetic, hypertensive, and to have undergone procedures involving more than one vein (24% vs 4%; P < .0001). Patients who underwent EVLA were more likely to have received general anesthesia (56.9% vs 40.8%; P < .0001) and to have undergone concomitant stab phlebectomy (44.9% vs 31.7%; P < .0001). The incidences of DVT (1.74% vs 1.52%; P = .63) and pulmonary embolus (0.07% vs 0%; P >.99) were similar between EVLA and RFA. No significant predictors of DVT in the postoperative period were identified on bivariate or multivariate analyses. In the subgroup of 2514 patients who underwent ablation procedures without stab phlebectomy, those undergoing EVLA showed a trend toward a higher incidence of DVT (2.6% vs 1.4%; P = .057). After adjusting for patient demographics, DVT was 2.4 times more likely to develop in patients presenting with lower extremity ulcers than in those without ulcers (odds ratio, 2.4; 95% confidence interval, 1.01-6.11; P = .04). Although not statistically significant, the multivariate model found that when only ablation procedures were performed, EVLA was associated with an 83% increase in odds of DVT compared with RFA (odds ratio, 1.83; 95% confidence interval, 0.95-3.52; P = .06). CONCLUSIONS: The incidence of venous thromboembolic events after saphenous ablation is low. However, given that patients with lower extremity ulcers experienced an increased risk of DVT, care should be taken to ensure that the ablation catheter is positioned an appropriate distance from the saphenofemoral or sapheno-popliteal junction and that periprocedural preventative measures, such as anticoagulation prophylaxis, early ambulation, and lower extremity compression, are emphasized. The finding of a trend toward increased venous thromboembolic events in patients undergoing EVLA warrants further investigation in a large patient population. PMID- 26993891 TI - Isolated calf muscular vein thrombosis is associated with pulmonary embolism and a high incidence of additional ipsilateral and contralateral deep venous thrombosis. AB - OBJECTIVE: Little is known about the natural history of isolated gastrocnemial and soleal vein thrombosis (IGSVT), and recommendations for treatment and follow up are therefore anecdotal. This study sought to determine the rates of venous thromboembolism (VTE) progression and resolution and the effect of antithrombotic therapy in patients with IGSVT. METHODS: A vascular laboratory database was queried from January 2002 to December 2006 to identify patients with duplex diagnosed IGSVT and follow-up duplex scan studies. Duplex scan examinations were reviewed to determine rates of resolution and development of new ipsilateral and contralateral VTE. Records were reviewed for comorbid conditions, VTE risk factors, anticoagulation therapy, the effect of anticoagulation on resolution of IGSVT, and diagnosis of pulmonary embolism (PE) confirmed by computed tomographic angiography. RESULTS: Patients with at least one follow-up duplex scan study were included in our analysis. Sixty-five limbs with isolated IGSVT were identified in 57 patients with follow-up duplex scans (mean, 2.75 studies per patient; mean follow-up, 113 days). Twenty patients (35%) received therapeutic anticoagulation after the IGSVT diagnosis. There were seven PEs, two on the same day as initial IGSVT diagnosis, and two within 1 week of diagnosis. IGSVT resolution rates by Kaplan-Meier analysis at 1 and 3 months were 20% and 41%, respectively. Eleven patients (19%) developed additional ipsilateral deep venous thrombosis (DVT; three axial calf vein thromboses and five proximal DVT) or contralateral DVT (one axial calf vein thrombosis [CVT], one IGSVT, and one proximal DVT) during follow up. Of the eight patients who developed additional ipsilateral DVT, five also developed concurrent contralateral DVT. Overall, 14% of patients developed contralateral DVT. Median time to development of additional DVT was 10 days. Therapeutic anticoagulation was associated with DVT resolution. However, VTE recurrence was not significantly affected by age, gender, anticoagulation, oral contraceptives, known hypercoagulable states, or comorbidities (smoking, cancer, trauma, postsurgical status, renal failure, hyperlipidemia, diabetes, or cardiopulmonary abnormalities; P > .05). CONCLUSIONS: Isolated calf muscular vein thrombosis is associated with PE and a significant incidence of VTE progression. Therapeutic anticoagulation is associated with DVT resolution, but its effect on VTE recurrence was not demonstrated. Untreated patients with IGSVT should receive follow-up bilateral lower extremity venous duplex scans within 10 days of diagnosis. PMID- 26993892 TI - Chronic venous insufficiency in patients with absence of the inferior vena cava. AB - OBJECTIVE: Up until now, knowledge of absence of the inferior vena cava (AIVC) is limited to case reports and small case series, usually reported shortly after diagnosis. To characterize long-term evolution of outcomes of patients with AIVC, we performed a survey of current practice in Belgium, The Netherlands, and Luxembourg (Benelux). METHODS: Vascular surgeons and phlebologists in the Benelux area were asked to complete a questionnaire on medical history and treatment of each patient in follow-up at their practice with a diagnosis of AIVC. RESULTS: The Benelux survey yielded 35 patients with AIVC, with a follow-up ranging from 0 to 28 years. Their median age was 40 years (range, 14-65 years), and 26 (74%) were male. Diagnosis of AIVC was made in 26 patients at the time of presentation with deep vein thrombosis (DVT). DVT was bilateral in 15 patients and involved one or both iliac veins in 21 (81% of all AIVC patients with acute DVT). Computed tomography scanning was used to detect AIVC in 29 patients. Thrombophilia was present in 16 (46%). The CEAP C classification was C4-6 in 17 right legs (49%) and 15 left legs (43%). Unilateral or bilateral ulceration had occurred in 11 patients in the past, and three had active ulceration. Long-term conservative treatment consisted of oral anticoagulant treatment in 28 patients and compression stockings in 27. CONCLUSIONS: The results of this survey on AIVC illustrate the unfavorable long-term clinical evolution of these patients. They frequently present with advanced stages of chronic venous insufficiency at a relatively young age, with the development of unilateral or bilateral extensive DVT and subsequent moderate to severe post-thrombotic syndrome. PMID- 26993893 TI - Contemporary results after sapheno-popliteal bypass for chronic femoral vein occlusion. AB - BACKGROUND: Chronic occlusion of the femoral or the proximal popliteal vein responsible for venous obstruction and the constellation of clinical sequelae that ensue remains a surgical challenge that carries notable patient morbidity. Sapheno-popliteal bypass (SPB) remains a surgical reconstructive option for select patients that demonstrate patency of the popliteal vein, great saphenous vein, saphenofemoral junction, and iliac veins. We sought to analyze our single institution experience with this technique. METHODS: A retrospective review of a single-center experience with SPB was performed. Preoperative risk factors and indications for intervention (ie, venous claudication, ulceration) were identified. Duration of follow-up and endpoints, including clinical improvement, wound healing, patency, and limb loss were assessed. A Kaplan-Meier analysis for primary and secondary patency was performed. RESULTS: Seventeen patients underwent SPB for chronic lower extremity venous obstruction between July 1988 and August 2011. Median age at operation was 41 years (range, 23-69 years). There was a male predominance noted (n = 12; 71%). All patients had chronic edema and venous claudication. Five patients (29%) had evidence of venous ulceration preoperatively. Eight patients (47%) underwent a preceding venous intervention (ie, iliac stenting or venous thrombolysis). Three patients had a concomitant arteriovenous fistula, created at the time of bypass to enhance in-flow; three patients underwent concomitant femoral-femoral venous bypass. Four patients (24%) experienced hematoma postoperatively that required operative evacuation; in two patients, compression from this hematoma resulted in early graft occlusion. After a median follow-up of 103 months (range, 3-271 months), 82% of patients experienced near or complete resolution of venous claudication. Three of the five patients with venous ulceration healed their wounds (67%). Of the 16 patients that underwent Duplex scan follow-up, primary patency after a median follow-up of 103 months was 56%, primary-assisted patency was 69%, and secondary patency was 75%. One patient required amputation approximately 21 years after SPB and there were no deaths. This secondary patency rate exceeds previously published patency rates. CONCLUSIONS: SPB may be indicated for certain patients with chronic venous stasis disease secondary to femoral venous obstruction that have failed other standard therapies. SPB remains a satisfactory and reliable procedure that produces clinical improvement in a selected group of patients and should be considered in a contemporary venous surgical practice. PMID- 26993894 TI - Midterm results of percutaneous endovascular treatment for acute and chronic deep venous thrombosis. AB - BACKGROUND: Treatment of deep venous thrombosis (DVT) with therapeutic anticoagulation has been increasingly challenged by aggressive percutaneous treatment using ultrasound-accelerated catheter-directed thrombolysis (US-CDT) or percutaneous pharmacomechanical thrombectomy (PMT). These techniques have been promoted to improve thrombus removal, prolong venous patency, prevent venous insufficiency, and reduce postthrombotic syndrome. This study reviews midterm results using these endovascular techniques for both acute and chronic DVT. METHODS: A retrospective chart review was performed on patients treated for acute or chronic DVT with US-CDT and/or PMT. Charts were reviewed for patient demographics, medical history and treatment, operative details, and postoperative outcomes. Intraoperative venography and intravascular ultrasound quantified clot response to therapy. Duplex ultrasound defined the pre- and postoperative extent of venous thrombosis, venous patency, and valvular function. RESULTS: Between October 1, 2002 and September 30, 2010, 80 patients were treated for iliofemoral (n = 48), iliofemoropopliteal (n = 15), or femoropopliteal (n = 17) venous thrombosis. Mean age was 45.8 years (range, 15-78 years), and 24 patients (30%) had a documented history of hypercoagulable state. Intravascular ultrasound confirmed May-Thurner syndrome in 34 patients (42.5%). Fifty-two patients (65%) were treated for acute DVT; the mean time to intervention from symptom onset was 8.7 +/- 4.5 days (range, 1-14 days). The remaining 28 patients (35%) had chronic symptoms and were treated at a mean of 8.6 +/- 10.9 months (range, 1.5-36 months) after DVT diagnosis was made. Patients were treated with PMT (n = 43, 53.8%), US CDT (n = 14, 17.5%), or both (n = 32, 28.7%). Clot lysis (>90%) was achieved in 72 of 80 patients (90%). Tenecteplase was used for all cases, and the mean dose was 8.6 +/- 4.3 mg. Adjunctive procedures, including angioplasty with or without stent placement, were required in 90% (n = 47) of acute patients and in 96% (n = 27) of chronic patients (P = .33). Three patients (3.8%) had postoperative bleeding events requiring blood transfusion; there were no occurrences of intracranial hemorrhage or clinically significant pulmonary embolism. At a mean follow-up of 3.8 years (range, 1-8.9 years), venous patency was present in 49 of 52 acute patients (94%) and in 23 of 28 chronic patients (82%) (P = .12). Valve function was preserved in 41 of 52 (79%) acute patients vs 11 of 28 (39%) chronic patients (P < .001). CONCLUSIONS: US-CDT and PMT can effectively remove acute and chronic thrombus in the lower extremity deep venous system. Vein patency and valvular function is better preserved at midterm follow-up after treatment for acute DVT, however intervention should be considered in patients with chronic DVT as well. PMID- 26993895 TI - Discussion. PMID- 26993897 TI - Evaluation of embolic protection devices for fat emboli prevention. AB - BACKGROUND: Patients with acutely treated femoral shaft fractures with reamed intramedullary nailing are at risk for acute respiratory distress syndrome due to liberation of bone marrow fat particles that travel to the lung and cause damage to the parenchyma. The purpose of this study was to demonstrate: (1) the ability of clinically applicable embolic protection devices to capture such particles; (2) how such a device affects cardiopulmonary function after reamed intramedullary nailing; and (3) evaluation of lung pathology to determine whether filtration affects pulmonary embolic load. METHODS: A total of 12 canines were anesthetized, and hemodynamic monitoring was established. Carotid embolic protection devices were introduced into the iliac vein, and ipsilateral intramedullary reaming and nailing was performed. Cardiopulmonary parameters were recorded at timed intervals up to 60 minutes after the procedure. The control group (n = 4) was compared with groups treated with Accunet (n = 4) and Spider (n = 4) filters. A blinded histopathological review was performed on lung specimens to determine the average number of emboli per section and to measure the area (mm(2)) of embolic load by digital image analysis. RESULTS: Gross inspection of the embolic protection devices showed the presence of bone marrow debris. A significant change was observed in pH levels (control = -0.052, filters = +0.005; P < .05) within the 60 minutes after intramedullary nailing. Serum bicarbonate (meq/dL) values were noted to have similar changes of -2.7 and -1.8 at 10 and 60 minutes, whereas the experimental group was +0.6 and +0.8 at the same time intervals (P =.01 and .0004, respectively). Pulmonary measurements for pO2 and oxygen saturation were analogous to the serum parameters with decreases in the control group in comparison with the filter groups. The mean numbers of emboli and area measurements of embolic load were significantly reduced in the filter group (all P < .01). CONCLUSIONS: Embolic protection devices were effective in capturing embolic debris from reamed intramedullary nailing of lower extremity long bones and demonstrated a protective effect on pulmonary function and significantly decreased the number and size of emboli in the lung. Based on these findings, patients with long bone fractures at risk for pulmonary complications and acute respiratory distress syndrome could benefit from the placement of embolic protection devices prior to intramedullary fixation. While this study utilized filtration devices designed for carotid embolic protection, further study is warranted to determine optimal filter design in this setting. PMID- 26993896 TI - Incidence of chronic venous disease in the Edinburgh Vein Study. AB - BACKGROUND: Epidemiologic research in chronic venous disease has focused on prevalence and associated risk factors. Evidence on the risks and incidence that this condition will develop is limited. The aim of this study was to measure the incidence of new varicose veins and chronic venous insufficiency (CVI) in an adult population and to investigate risk factors associated with the development of these conditions. METHODS: The Edinburgh Vein Study is a cohort study of a random sample of the general population. Invitations were sent to 1456 men and women at baseline to participate in a 13-year follow-up examination. Each participant completed a questionnaire on lifestyle and medical history and underwent an examination that included clinical classification of venous disease. RESULTS: After a mean follow-up of 13.4 (standard deviation, 0.4) years, 880 of 1456 individuals participated (60.4% response). The overall incidence (95% confidence interval [CI]) of C2 varicose veins was 18.2% (15.2%-21.6%), giving an annual incidence rate of 1.4% (1.1%-1.7%), with incidence rates similar in men and women: the 13-year age-adjusted incidence of varicose veins was 15.2% (10.4% 20.0%) in men and 17.4% (13.1%-21.7%) in women (P = .97). The 13-year incidence of varicose veins increased consistently with age from 9.8% in those aged 18 to 34 years to 25.7% in those aged 55 to 64 years (P < .001). The 13-year incidence (95% CI) of CVI was 9.2% (7.0%-11.9%), and the annual incidence rate was 0.7% (0.5%-0.9%). The incidence of CVI was similar in men and women and increased consistently with age (P < .001). Participants with a family history of venous disease were more likely to develop C2 varicose veins (odds ratio, 1.75; 95% CI, 1.12-2.71). Obesity was associated with the development of CVI: the 13-year incidence (95% CI) was 6.1% (3.7%-9.6%) in those who were of normal weight and 23.6% (14.2%-37.0%) in obese participants, with an age-adjusted odds ratio of 3.58 (1.70-7.56). CONCLUSIONS: The Edinburgh Vein Study is one of a few cohort studies to report the incidence of varicose veins and CVI in the general population. The incidence of varicose veins and CVI did not differ significantly by sex and was strongly associated with increasing age. The risk of developing varicose veins was increased in those with a family history, and the risk of CVI was increased in those with higher body mass index. PMID- 26993898 TI - Inferior vena cava epithelioid hemangioendothelioma. AB - Epithelioid hemangioendotheliomas are rare endothelial tumors that may manifest in a multitude of anatomic locations. The inferior vena cava (IVC) is an unusual site of primary tumor, with only two cases reported to date. We present a patient with an IVC epithelioid hemangioendothelioma who required IVC resection and lymphadenectomy. The patient made a good recovery and remains disease-free 4 years after resection. IVC tumors represent a unique challenge, not the least because of this tumor's unpredictable and, at present, undefined behavior, but also owing to the vital anatomic structures requiring definitive surgical excision. PMID- 26993899 TI - The utility of dynamic magnetic resonance venography in the setting of pelvic venous pathology. AB - The standard initial noninvasive imaging modality for diagnosing May-Thurner syndrome is duplex ultrasound, but this modality provides only indirect measures and is frequently limited, necessitating further imaging to make the diagnosis. Other noninvasive imaging modalities (computed tomographic venography, time of flight, magnetic resonance venography) allow for direct visualization but lack hemodynamic and anatomic information about what is occurring throughout the cardiac cycle. Intravascular ultrasound is the invasive tool of choice in the setting of iliac vein compression syndrome, but quality, noninvasive imaging modalities have yet to be described. Contrast-enhanced, dynamic magnetic resonance venography allows for detailed imaging of the pelvis as well as dynamic vascular imaging, improving preoperative planning. PMID- 26993900 TI - Great saphenous vein transposition to the popliteal vein (the May-Husni procedure). PMID- 26993901 TI - Techniques for inferior vena cava resection and reconstruction for retroperitoneal tumor excision. AB - Management of the inferior vena cava (IVC) after resection for treatment of retroperitoneal sarcomas is controversial. Ligation is well tolerated if collateral circulation is preserved. These pathways, however, are often interrupted or resected during tumor excision, and up to 50% of these patients will experience lower extremity edema with IVC ligation. We have favored IVC reconstruction, particularly when circumferential resection is necessary for complete retroperitoneal tumor removal. Our results with this approach have been recently updated, documenting that en bloc resection and reconstruction of the IVC can be performed with very low morbidity and mortality and is associated with a low incidence of postoperative symptoms of venous hypertension. This article describes our preferred techniques for the management of the IVC after partial or circumferential resection. PMID- 26993902 TI - A survey of current practice of vascular surgeons in venous disease management. AB - OBJECTIVE: Acute venous thromboembolism and chronic venous diseases are common conditions that affect a large proportion of the United States population. The diagnosis of venous disease has improved, and the treatment options have rapidly evolved over the past decade. To date, it is unclear to what extent vascular surgeons have become involved in the modern management of venous disorders. This survey was undertaken to explore the current interest and practice of vascular surgeons in the contemporary care of venous disease. METHODS: A survey was administered via a web-based platform to active and candidate members of the Society for Vascular Surgery (SVS). The survey included 30 questions investigating the characteristics of venous surgeons and scope of venous practice. Open-ended questions were also included for commentary. RESULTS: A total of 1879 surveys were sent to SVS members nationwide, and 385 members participated (response rate of 20.5%). The participants were mostly men (89.6%) with 37.7% practicing in an academic setting and 59.2% in private practice. The respondents treated superficial veins (92.9%) and deep veins (85.8%) in clinical practice, with 89.9% having their own vascular laboratory. A wide spectrum of interventions for superficial (91.9%), deep (85.8%), and perforator veins (52.7% endovenous, 19.4% subfascial endoscopic perforator surgery) are being performed by respondents. Only 26.2% had learned endovenous thermal ablation in their training program; however, over 96% of those performing venous interventions utilized this technique. Overall, the majority (85.5%) devoted 50% or less of practice to venous disorders. Respondents indicated that limitations to expansion of vein practices mainly involved challenges with third party payers, local competition, and existing large volumes of arterial interventions needing to be performed. Despite the widespread incorporation of venous disease into current vascular practices, 66.1% are not members of the American Venous Forum (AVF) or other venous society. Many believe there is still a lack of standardization of care and guidelines for venous disease. CONCLUSIONS: The care of patients with venous disease has become more widespread among SVS members, with most offering both deep and superficial venous interventions as well as incorporation of minimally invasive techniques into their treatment armamentarium. Dissemination and incorporation of protocols and guidelines into clinical practice as well as postgraduate courses in venous disease may be areas in which the SVS could facilitate members' involvement in the care of patients with venous disease. PMID- 26993903 TI - Leg ulcers of venous origin: From ancient to modern times. PMID- 26993904 TI - Pelvic Venous Reflux is a Major Contributory Cause of Recurrent Varicose Veins in more than a Quarter of Women. PMID- 26993905 TI - Management Trends for Chronic Venous Insufficiency Across the United States: A Report from the American Venous Registry. PMID- 26993906 TI - Creation of a Simple VTE Risk Stratification Tool for Inpatient Surgical Procedures. PMID- 26993907 TI - Big Veins, Big Deal - Vein Diameter Affects Disease Severity, not Quality of Life. PMID- 26993908 TI - Influence on Chronic Venous Insufficiency of Primary Absence of the Great Saphenous Vein in the Saphenous Compartment at the Thigh. PMID- 26993909 TI - The European Multicenter Study on Cyanoacrylate Embolization of Refluxing Great Saphenous Veins without Tumescent Anesthesia and without Compression Therapy. PMID- 26993910 TI - Galectin-3 Binding Protein and Galectin-3: Novel Factors Promoting Venous Thrombosis. PMID- 26993911 TI - Patients Who Are Transferred from Other Hospitals Have Higher Incidence of DVT. PMID- 26993912 TI - Natural History of Deep Vein Thrombosis in Children. PMID- 26993913 TI - Vitronectin Gene-deletion, PAI-1 Gene-deletion, and LMWH Treatment: Effect on Thrombus Resolution and Vein Wall Remodeling in a Mouse Model of DVT. PMID- 26993915 TI - Prolonged Radiation Exposure in IVC Filter Removal. PMID- 26993914 TI - Iron Processing Mechanisms are Responsible for Changes in MRI T1 Relaxation in Venous Thrombosis. PMID- 26993916 TI - Validation of the Villalta Scale in Assessing Post-thrombotic Syndrome using Clinical, Duplex, and Hemodynamic Comparators. PMID- 26993917 TI - Anticoagulation Treatment for Catheter-associated Upper Extremity Deep Venous Thrombosis (CA-UEDVT): Assessment of Risk and Benefits. PMID- 26993918 TI - Prolonged Mechanical Stretch Alters the Metabolic Profile in Rat Inferior Vena Cava. PMID- 26993919 TI - The Real Costs of Treating Venous Ulcers in a Contemporary Vascular Practice. PMID- 26993920 TI - American Venous Registry - The First National Registry for the Treatment of Varicose Veins. PMID- 26993921 TI - Endovenous Laser Ablation versus Conventional Surgery in the Treatment of Small Saphenous Vein Incompetence: Short-Term Results of a Multicenter Randomized Controlled Trial. PMID- 26993922 TI - Measurements of Calf Muscle Oxygenation during Standing and Exercise in Patients with Chronic Venous Insufficiency. PMID- 26993923 TI - Relationship between Tissue Pressures and Disease Severity in Venous Disease. PMID- 26993924 TI - The Role of Duplex Ultrasound in the Pelvic Congestion Syndrome Workup. PMID- 26993925 TI - Use of Compression Therapy in Patients with Chronic Venous Insufficiency Undergoing Ablation Therapy: A Report from the American Venous Registry. PMID- 26993926 TI - Oscillatory Turbulent Flow in Chronic Venous Disease Induces Pro-inflammatory and Reparative Biological Signaling. PMID- 26993927 TI - ISOL-8: A Multicenter, Retrospective Study of the Effectiveness of the Trellis-8 to Treat Iliofemoral DVT and Prevent Post-thrombotic Syndrome. PMID- 26993928 TI - The Importance of IVUS Assessment in Venous Thrombolytic Regimens. PMID- 26993929 TI - Relationship between Medical Compression and Intramuscular Pressure - Explanation of a Paradox of Compression. PMID- 26993930 TI - Catheter-Directed Thrombolysis for Patients with Massive and Submassive Pulmonary Embolism. PMID- 26993931 TI - Using a Fibrin-targeted Molecular Magnetic Resonance Imaging to Identify Venous Thrombi Susceptible to Thrombolysis. PMID- 26993932 TI - Blood Type and Postthrombotic Syndrome: Early Indication for Endovascular Treatment. PMID- 26993933 TI - Inferior Vena Cava Endovascular Reconstructions: Fifteen Years of Experience. PMID- 26993935 TI - Managing the Iliac-caval Confluence in Iliac Vein Stenting. PMID- 26993934 TI - Classification of Anatomic Involvement of the Ilio-caval Venous Outflow Tract and Its Relationship to Early Outcomes after Ilio-caval Venous Stenting. PMID- 26993936 TI - Hemodynamic Changes in the Femoral Vein with Increasing Outflow Resistance. PMID- 26993938 TI - Foam Washout Sclerotherapy: A New Technique Geared Toward Reducing Short- and Long-term Complications of Regular Foam Sclerotherapy and Comparison with Existing Foam Sclerotherapy Method. PMID- 26993937 TI - Characterization of Chronic Postthrombotic Intraluminal Venous Obstruction. PMID- 26993940 TI - Value of a Diagnostic Score Ascribing Leg Symptoms to Chronic Venous Disorders in Patients Undergoing Surgery for Varicose Veins. PMID- 26993939 TI - Negotiations with Health Insurers Can Lead to Positive Changes in Policies Towards Venous Disease. PMID- 26993941 TI - Venous Center Accreditation - An Initiative for Improving Patient Care. PMID- 26993942 TI - Reflux in the Below-knee Great Saphenous Vein Can Be Safely Treated with Endovenous Ablation. PMID- 26993943 TI - Abundant Pericytes in the Venous Intima and the Vasa Venarum: Evidence for Their Key Role in Venous Thrombosis. PMID- 26993944 TI - Three-dimensional Ultrasound Assessment of DVT Volume: A Clinical Protocol and Description of the Time-course of Thrombus Resolution. PMID- 26993946 TI - Assessment of the Postthrombotic Syndrome using MR Venography and DUS: The Correlation with Clinical Scoring Systems, VCSS, Villalta, and CEAP. PMID- 26993945 TI - Vein Wall and Circulating P-selectin Promote Venous Thrombogenesis During Aging in a Rodent Model. PMID- 26993947 TI - The Thrombotic Reactivity of Endothelial Cells from Deep Vein and Pulmonary Artery Venous Beds in Response to Thrombin. PMID- 26993948 TI - Radiologic Classification of Iliac Vein Compression and Patterns of Pelvic Collateralization in Patients with Chronic Venous Disease. PMID- 26993949 TI - Surgical Desobstruction of the Common Femoral Vein in Deep Venous Occlusive Disease. PMID- 26993950 TI - Information for readers. PMID- 26993951 TI - Editorial policies. PMID- 26993952 TI - Events of interest. PMID- 26993954 TI - Countering effects of a combination of podophyllotoxin, podophyllotoxin beta-D glucoside and rutin hydrate in minimizing radiation induced chromosomal damage, ROS and apoptosis in human blood lymphocytes. AB - The present study was conceptualized with the aim of developing a safe radioprotector for human application against radiation induced toxicity. For this study, a formulation (G-002M) prepared by combining three active principles isolated from rhizomes of Podophyllum hexandrum, was evaluated for its potential to protect genomic DNA of human blood cells exposed to different doses of radiation (5,7&10Gy). Blood samples were pretreated (-1hr to exposure) with G 002M. Parameters of Premature Chromosome Condensation (PCC) assay like PCC-index, PCC-rings and PCC-fragments were used to estimate radiation induced chromosomal aberrations. Radiation (7Gy) induce ROS generation and its modulation by G-002M was determined by flow-cytometry and fluorescent microscopy while apoptosis (0,2,24&48 hr) was analyzed using TUNEL assay. Effect on spindle organization in G2/M arrested cells by all the three compounds individually was studied using immunofluorescence microscopy. Irradiation caused dose dependent linear increase in PCC-rings and fragments, while decline in PCC index. G-002M pretreatment significantly decreased these chromosomal aberrations at all the radiation doses and assisted cell survival as indicated by increased PCC index compared with radiation only group. Significant decrease in radiation induced intracellular ROS (45 +/- 3%) and apoptosis (49.9%) was also exhibited by the formulation. On podophyllotoxin treatment, most of the cells have shown blocked spindles however, depicted normal arrangement. G-002M also demonstrated a highly significant Dose Modifying Factor or DMF (PCC-rings: 2.27 and PCC-fragments: 1.60). Present study based on many parameters along with DMF study, strongly suggests that G-002M is an effective formulation with a potential to minimize chromosomal damage even at very high radiation doses. PMID- 26993955 TI - Daphnia magna negatively affected by chronic exposure to purified Cry-toxins. AB - Cry-toxin genes originating from Bacillus thuringiensis are inserted into genetically modified (GM) plants, often called Bt-plants, to provide insect resistance to pests. Significant amounts of Bt-plant residues, and thus Cry toxins, will be shed to soil and aquatic environments. We exposed Daphnia magna to purified Cry1Ab and Cry2Aa toxins for the full life-span of the animals. We used single toxins in different doses and combinations of toxins and Roundup((r)), another potential stressor on the rise in agricultural ecosystems. Animals exposed to 4.5 mg/L (ppm) of Cry1Ab, Cry2Aa and the combination of both showed markedly higher mortality, smaller body size and very low juvenile production compared to controls. Animals exposed to 0.75 mg/L also showed a tendency towards increased mortality but with increased early fecundity compared to the controls. Roundup((r)) stimulated animals to strong early reproductive output at the cost of later rapid mortality. We conclude that i) purified Cry toxins in high concentrations are toxic to D. magna, indicating alternative modes of-action for these Cry-toxins; ii) Cry-toxins act in combination, indicating that 'stacked events' may have stronger effects on non-target organisms; iii) further studies need to be done on combinatorial effects of multiple Cry-toxins and herbicides that co-occur in the environment. PMID- 26993956 TI - Acid-labile protein-adducted heterocyclic aromatic amines in human blood are not viable biomarkers of dietary exposure: A systematic study. AB - Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of protein-rich foods. HCA residues adducted to blood proteins have been postulated as biomarkers of HCA exposure. However, the viability of quantifying HCAs following hydrolytic release from adducts in vivo and correlation with dietary intake are unproven. To definitively assess the potential of labile HCA protein adducts as biomarkers, a highly sensitive UPLC-MS/MS method was validated for four major HCAs: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2 amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8 trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,7,8 trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx). Limits of detection were 1-5 pg/ml plasma and recoveries 91-115%. Efficacy of hydrolysis was demonstrated by HCA-protein adducts synthesised in vitro. Plasma and 7-day food diaries were collected from 122 fasting adults consuming their habitual diets. Estimated HCA intakes ranged from 0 to 2.5 mg/day. An extensive range of hydrolysis conditions was examined for release of adducted HCAs in plasma. HCA was detected in only one sample (PhIP, 9.7 pg/ml), demonstrating conclusively for the first time that acid labile HCA adducts do not reflect dietary HCA intake and are present at such low concentrations that they are not feasible biomarkers of exposure. Identification of biomarkers remains important. The search should concentrate on stabilised HCA peptide markers and use of untargeted proteomic and metabolomic approaches. PMID- 26993957 TI - Predictive Strength of Self-Rated Health for Mortality Risk Among Older Adults in the United States: Does It Differ by Race and Ethnicity? AB - Self-rated health (SRH) is widely used to capture racial and ethnic disparities in health. It is therefore critical to understand whether individuals with different racial and ethnic backgrounds assess their SRH differently. Despite the high overall predictive validity of SRH for subsequent mortality, few studies paid attention to potential variations by race and ethnicity. This study examines racial and ethnic differences in the predictive validity of SRH for subsequent mortality risk among older adults (55-84) by estimating Cox Proportional Hazard models using data from the National Health Interview Surveys Linked Mortality Files (1989-2006; N = 289,432). Results indicate that SRH predicts mortality risk less well for non-Hispanic Blacks and Hispanics than non-Hispanic Whites. Three proposed mechanisms-socioeconomic status, immigration status, and cause of death explain only a modest proportion of the variation. These results suggest that individuals from different racial and ethnic groups may evaluate their heath differently, and thus caution is necessary when using SRH to estimate racial and ethnic health disparities. PMID- 26993958 TI - [The circadian system in man: From the internal clock to melatonin secretion]. AB - The internal or biological clock which is located in the suprachiasmatic nuclei of the anterior hypothalamus is controlled by clock genes and environmental factors which are able to synchronize the clock to 24h. Rhythm desynchronization (shiftwork and nightwork, transmeridian flights, aging, some psychiatric diseases, blindness, intake of some drugs...) occurs when the internal clock does no longer work in harmony with the astronomical time i.e. our watch. The circadian system consists of three major elements, which are the clock, the retinohypothalamic tract and melatonin which is secreted by the pineal gland and considered as the arrow of the clock. Both light and melatonin present a phase response curve useful for the treatment of sleep circadian disorders. PMID- 26993961 TI - Implementation of an artificial neural network as a PAT tool for the prediction of temperature distribution within a pharmaceutical fluidized bed granulator. AB - In this study, a novel in-line measurement technique of the air temperature distribution during a granulation process using a conical fluidized bed was designed and built for the purpose of measuring the temperature under the Process Analytical Technology (PAT) and introduced to predict the establishment of temperature profiles. Three sets of thermocouples were used, placed at different positions covering the whole operating range, connected to data acquisition measurement hardware, allowing an in-line acquisition and recording of temperatures every second. The measurements throughout the fluidized bed were performed in a steady state by spraying a solution of PVP onto a lactose monohydrate powder bed in order to make predictions of the temperature distribution and the hydrodynamics of the bed during the granulation process using Artificial Neural Networks (ANNs) and to establish the different temperature profiles for different process conditions through the precise predicted information by the constructed, trained, validated and tested neural network. The model's testing results showed a strong prediction capacity of the effects of process variables. Indeed, the predicted temperature values obtained with the ANN model were in good agreement with the values measured with in-line reference method and hence the method can have an application as a predictive control tool. PMID- 26993959 TI - Reduced Modulation of Pain in Older Adults After Isometric and Aerobic Exercise. AB - Laboratory-based studies show that acute aerobic and isometric exercise reduces sensitivity to painful stimuli in young healthy individuals, indicative of a hypoalgesic response. However, little is known regarding the effect of aging on exercise-induced hypoalgesia (EIH). The purpose of this study was to examine age differences in EIH after submaximal isometric exercise and moderate and vigorous aerobic exercise. Healthy older and younger adults completed 1 training session and 4 testing sessions consisting of a submaximal isometric handgrip exercise, vigorous or moderate intensity stationary cycling, or quiet rest (control). The following measures were taken before and after exercise/quiet rest: 1) pressure pain thresholds, 2) suprathreshold pressure pain ratings, 3) pain ratings during 30 seconds of prolonged noxious heat stimulation, and 4) temporal summation of heat pain. The results revealed age differences in EIH after isometric and aerobic exercise, with younger adults experiencing greater EIH compared with older adults. The age differences in EIH varied across pain induction techniques and exercise type. These results provide evidence for abnormal pain modulation after acute exercise in older adults. PERSPECTIVE: This article enhances our understanding of the influence of a single bout of exercise on pain sensitivity and perception in healthy older compared with younger adults. This knowledge could help clinicians optimize exercise as a method of pain management. PMID- 26993962 TI - Transdermal film-loaded finasteride microplates to enhance drug skin permeation: Two-step optimization study. AB - The goal was to develop an optimized transdermal finasteride (FNS) film loaded with drug microplates (MIC), utilizing two-step optimization, to decrease the dosing schedule and inconsistency in gastrointestinal absorption. First; 3-level factorial design was implemented to prepare optimized FNS-MIC of minimum particle size. Second; Box-Behnken design matrix was used to develop optimized transdermal FNS-MIC film. Interaction among MIC components was studied using physicochemical characterization tools. Film components namely; hydroxypropyl methyl cellulose (X1), dimethyl sulfoxide (X2) and propylene glycol (X3) were optimized for their effects on the film thickness (Y1) and elongation percent (Y2), and for FNS steady state flux (Y3), permeability coefficient (Y4), and diffusion coefficient (Y5) following ex-vivo permeation through the rat skin. Morphological study of the optimized MIC and transdermal film was also investigated. Results revealed that stabilizer concentration and anti-solvent percent were significantly affecting MIC formulation. Optimized FNS-MIC of particle size 0.93MUm was successfully prepared in which there was no interaction observed among their components. An enhancement in the aqueous solubility of FNS-MIC by more than 23% was achieved. All the studied variables, most of their interaction and quadratic effects were significantly affecting the studied variables (Y1-Y5). Morphological observation illustrated non-spherical, short rods, flakes like small plates that were homogeneously distributed in the optimized transdermal film. Ex-vivo study showed enhanced FNS permeation from film loaded MIC when compared to that contains pure drug. So, MIC is a successful technique to enhance aqueous solubility and skin permeation of poor water soluble drug especially when loaded into transdermal films. PMID- 26993960 TI - The Longitudinal Impact of Parent Distress and Behavior on Functional Outcomes Among Youth With Chronic Pain. AB - Accumulating evidence supports the concurrent association between parent distress and behavior and child functioning in the context of chronic pain, with existing longitudinal studies limited to a pediatric surgical context that identify parent catastrophizing as influential. In this study, we examined how parent factors assessed at a multidisciplinary pediatric pain clinic evaluation affect child psychological and functional outcomes over time. A cohort of 195 patients with chronic pain (ages 8-17 years) and their parents who presented for a multidisciplinary evaluation completed measures at baseline and at 4-month follow up. Patients completed measures of pain catastrophizing, pain-related fear and avoidance, generalized anxiety, depressive symptoms, and functional disability. Parents completed measures of pain catastrophizing, pain-related fear and avoidance, and protective responses to child pain. Parent-reported child school functioning was also collected. Parent distress and behavior was concurrently associated with child distress and functioning at evaluation. After controlling for baseline child functioning, baseline parent avoidance and protective behavior emerged as significant predictors of child functioning at 4-month follow-up. Parent distress and behavior influence child distress and functioning over time and these findings identify key parent domains to target in the context of a child's pain treatment. PERSPECTIVE: Parent behavior, specifically avoidance and protective responses, influence child distress and functioning over time. Child pain treatment interventions should include influential parent factors to ensure successful outcomes. PMID- 26993963 TI - (18)F-labeling syntheses and preclinical evaluation of functionalized nanoliposomes for Alzheimer's disease. AB - The aim of the present study was to synthesize functionalized (18)F-labeled NLs ((18)F-NLs) and evaluate their biological behavior in mouse models of Alzheimer's disease (AD) using positron emission tomography (PET) and ex vivo brain autoradiography. (18)F-fluorine was introduced to (18)F-NLs either by using a core forming (18)F-lipid or by encapsulating a (18)F-tracer, (18)F-treg-curcumin inside the NLs. Phosphatidic acid (PA) and curcumin derivative (Curc) functionalized (18)F-NLs with or without additional mApoE functionalization were produced using thin film hydration. The biodistribution and beta-amyloid plaque binding ability of (18)F-NLs were studied in wild type mice and AD mouse models using in vivo PET imaging and ex vivo brain autoradiography at 60min after (18)F NL injection. Functionalized (18)F-NLs were successfully synthesized. The preclinical evaluation in mice showed that the functional group affected the biodistribution of (18)F-NLs. Further functionalization with mApoE increased the brain-to-blood ratio of (18)F-NLs but the overall brain uptake remained low with all functionalized (18)F-NLs. The liposomal encapsulation of (18)F-treg-curcumin was not successful and preclinical results of encapsulated (18)F-treg-curcumin and plain (18)F-treg-curcumin were identical. Although the studied functionalized (18)F-NLs were not suitable for PET imaging as such, the synthesis techniques introduced in this study can be utilized to modify the biological behavior of (18)F-labeled NLs. PMID- 26993964 TI - Synthesis, In silico studies and In vitro evaluation for antioxidant and antibacterial properties of diarylmethylamines: A novel class of structurally simple and highly potent pharmacophore. AB - A series of novel diarylmethylamines were synthesized via simple three component condensation reaction. In vitro antibacterial activity of the synthesized compounds was assessed against Gram-positive and Gram-negative bacteria. Compound 1f containing phenyl and N-methyl piperazine moiety was found to be potent against both pathogenic bacteria with MIC value of 31MUg/mL. Diarylmethylamine 1l containing sesamol and N-methyl piperazine units was found to be the most effective against Gram-positive bacteria with MIC value of 15MUg/mL. The compound leads to the damage of the bacterial cell membrane which was demonstrated by flow cytometry (FC) and field emission scanning electron microscopy (FESEM). Radical scavenging activity of compounds 1l and 1m was found out to be comparable with that of standard antioxidant BHT. Further, in silico studies were carried out to calculate the physico-chemical parameter of the synthesized compounds. PMID- 26993965 TI - Prenatal diagnosis of bowel malposition using T2-weighted fetal MRI sequences. AB - OBJECTIVE: The goal of this study was to investigate the capability of T2 weighted magnetic resonance imaging (MRI) in revealing fetal bowel malposition. MATERIALS AND METHODS: All fetal MRI examinations (excluding central nervous system MRI examinations) performed in our department from January 2005 to January 2014 were retrospectively studied by 2 independent observers for situs, stomach and jejunum location on T2-weighted images. Patients data were also reviewed for results of ultrasound examinations, MRI indication, and gestational age. Abnormally positioned jejunums were classified into 3 groups: intrathoracic (A), extra-fetal (B) and abnormal intra-fetal (C). Prenatal data were compared to postnatal imaging, surgery or autopsy findings that served as standard of reference. RESULTS: A total of 709 fetal MRI examinations were analyzed. In 64 fetus (9%), the jejunum was not present in the left subgastric area on T2 weighted MR images. In these 64 fetuses, proximal jejunum was intrathoracic (41/64, 64%, group A), extra-fetal (11/64, 17%, group B), or intra-abdominal but abnormally positioned (12/64, 19%, group C). Interobserver agreement was 100%. All diagnoses for fetuses in groups A and B (52 cases) were confirmed postnatally (41 cases) or at autopsy (11 cases). In group C, bowel malposition was suspected after ultrasound in only 2/12 fetuses (16.6%); it was confirmed postnatally in 1 fetus but not confirmed in the remaining one. In the 10 remaining fetuses (83%), malposition was confirmed postnatally although not initially suspected. CONCLUSION: T2-weighted fetal MR images are useful for the prenatal diagnosis of bowel malposition, even when they are unsuspected on ultrasound examination. PMID- 26993966 TI - Imaging of postoperative tetralogy of Fallot repair. AB - Over the last years, the surgical techniques used to repair Tetralogy of Fallot as well as the cross-sectional cardiac imaging techniques have substantially improved. Now, the survival rate after surgical repair is more than 90% at 40 years old. A follow-up is needed and the imaging evaluation should be guided by the surgical techniques used. This article reviews the most common surgical procedures for a complete repair, the associated anatomic and hemodynamic complications and the role of cardiac imaging, mainly magnetic resonance imaging. PMID- 26993967 TI - Applications of dual energy computed tomography in abdominal imaging. AB - Dual energy computed tomography (CT) is an imaging technique based on data acquisition at two different energy settings. Recent advances in CT have allowed data acquisition and almost simultaneously analysis of two spectra of X-rays at different energy levels resulting in novel developments in the field of abdominal imaging. This technique is widely used in cardiovascular imaging, especially for pulmonary embolism work-up but is now also increasingly developed in the field of abdominal imaging. With dual-energy CT it is possible to obtain virtual unenhanced images from monochromatic reconstructions as well as attenuation maps of different elements, thereby improving detection and characterization of a variety of renal, adrenal, hepatic and pancreatic abnormalities. Also, dual energy CT can provide information regarding urinary calculi composition. This article reviews and illustrates the different applications of dual-energy CT in routine abdominal imaging. PMID- 26993968 TI - Natural Variation in Tomato Reveals Differences in the Recognition of AvrPto and AvrPtoB Effectors from Pseudomonas syringae. AB - The Pto protein kinase from Solanum pimpinellifolium interacts with Pseudomonas syringae effectors AvrPto or AvrPtoB to activate effector-triggered immunity. The previously solved crystal structures of the AvrPto-Pto and AvrPtoB-Pto complexes revealed that Pto binds each effector through both a shared and a unique interface. Here we use natural variation in wild species of tomato to further investigate Pto recognition of these two effectors. One species, Solanum chmielewskii, was found to have many accessions that recognize only AvrPtoB. The Pto ortholog from one of these accessions was responsible for recognition of AvrPtoB and it differed from Solanum pimpinellifolium Pto by only 14 amino acids, including two in the AvrPto-specific interface, glutamate-49/glycine-51. Converting these two residues to those in Pto (histidine-49/valine-51) did not restore recognition of AvrPto. Subsequent experiments revealed that a single substitution of a histidine-to-aspartate at position 193 in Pto, which is not near the AvrPto-specific interface, was sufficient for conferring recognition of AvrPto in plant cells. The reciprocal substitution of aspartate-to-histidine-193 in Pto abolished AvrPto recognition, confirming the importance of this residue. Our results reveal new aspects about effector recognition by Pto and demonstrate the value of using natural variation to understand the interaction between resistance proteins and pathogen effectors. PMID- 26993969 TI - Sleep Apnea and Fatty Liver Are Coupled Via Energy Metabolism. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by intermittent hypoxia. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease worldwide. We aimed to evaluate the relationship between OSA and fatty liver. MATERIAL/METHODS: We enrolled 176 subjects to this study who underwent polysomnography (PSG) for suspected OSA. The control group included 42 simple snoring subjects. PSG, biochemical tests, and ultrasonographic examination were performed all subjects. RESULTS: The simple snoring and mild, moderate, and severe OSA groups included 18/42 (42.86%), 33/52 (63.5%), 27/34 (79.4%), and 28/48 (79.2%) subjects with hepatosteatosis, respectively. There were significant differences in hepatosteatosis and hepatosteatosis grade between the simple snoring and the moderate and severe OSA groups. Logistic regression analysis showed that BMI and average desaturation were independently and significantly related to hepatic steatosis. CONCLUSIONS: Our study shows that BMI and the average desaturation contribute to non-alcoholic fatty liver in subjects with OSA. In this regard, sleep apnea may trigger metabolic mitochondrial energy associated processes thereby altering lipid metabolism and obesity as well. PMID- 26993970 TI - Pathways for making unisexual flowers and unisexual plants:Moving beyond the "two mutations linked on one chromosome" model. PMID- 26993971 TI - The orientation of foliicolous lichen campylidia with respect to water runoff and its significance for propagule dispersal. AB - PREMISE OF THE STUDY: Some common leaf-dwelling lichen fungi produce asexual spores (conidia) within curved, dorsiventral structures called campylidia. Their shape and tendency to face in the same direction have generated speculation about how dispersal is accomplished. Here we tested the hypothesis that campylidia orient their spore-producing surface against runoff currents and examined the effects of hydration to better understand the spore dispersal mechanism. METHODS: Palm leaves bearing lichens (Calopadia) were surveyed with a dissecting microscope for campylidia with fibrous debris entangled around the base. Where possible, the direction of runoff flow was inferred from the position of the entangled debris; the angle between this direction and that toward which the spore-producing side faced was calculated for 67 campylidia. Other fresh collected campylidia were photographed in the air-dry state and again after hydration. KEY RESULTS: Orientation of campylidia was strongly correlated with direction of runoff flow, such that the spore-producing side faced against oncoming runoff. Hydration of campylidia quickly resulted in swelling of the conidial mass beneath a thin flap of tissue covering the conidiogenous surface. The flap then bulged outward, exposing the conidial mass from above within its pocket-like compartment. CONCLUSIONS: Our results support previous contentions that water impact against campylidia is important in spore dispersal. However, the morphology of hydrated campylidia and their strong tendency to face upstream suggest that water currents impact laterally upon the thin tissue covering the hydrated conidial mass, thereby extruding spores apically. We contrast these findings with previous suggestions that campylidia act as splash cups. PMID- 26993972 TI - The amount of parenchyma and living fibers affects storage of nonstructural carbohydrates in young stems and roots of temperate trees. AB - PREMISE OF THE STUDY: Concentrations of nonstructural carbohydrates (NSCs) are used as proxies for the net carbon balance of trees and as indicators of carbon starvation resulting from environmental stress. Woody organs are the largest NSC storing compartments in forest ecosystems; therefore, it is essential to understand the factors that affect the size of this important storage pool. In wood, NSC are predominantly deposited in ray and axial parenchyma (RAP); however, direct links between nutrient storage and RAP anatomy have not yet been established. Here, we tested whether the NSC storage capacity of wood is influenced by the amount of RAP. METHODS: We measured NSC concentrations and RAP fractions in root and stem sapwood of 12 temperate species sampled at the onset of winter dormancy and in stem sapwood of four tropical trees growing in an evergreen lowland rainforest. The patterns of starch distribution were visualized by staining with Lugol's solution. KEY RESULTS: The concentration of NSCs in sapwood of temperate trees scales tightly with the amount of RAP and living fibers (LFs), with almost all RAP and LFs being densely packed with starch grains. In contrast, the tropical species had lower NSC concentrations despite their higher RAP and LFs fraction and had considerable interspecific differences in starch distribution. CONCLUSIONS: The differences in RAP and LFs abundance affect the ability of sapwood to store NSC in temperate trees, whereas a more diverse set of functions of RAP might be pronounced in species growing in a tropical environment with little seasonality. PMID- 26993973 TI - The effect of triiodothyronine on maturation and differentiation of oligodendrocyte progenitor cells during remyelination following induced demyelination in male albino rat. AB - Demyelination was induced by two weeks cuprizone treatment. Rats of +ve control and triiodothyronine (T3) then received three subcutaneous injections of either saline or T3 day after day and sacrificed at the end of the third and fifth weeks. Animals in -ve control group received only standard rodent chow. After one week of cuprizone withdrawal the corpus callosum in +ve control and T3 treated rats was still demyelinated as revealed by MBP immunohistochemistry. The assay of PLP gene showed significant increase of T3 treated group compared to both the -ve control and +ve control groups. After three weeks, significant improvement in myelination was detected in T3-treated group compared to +ve control as detected by both MBP immunohistochemistry and electron microscopy. After one week of cuprizone withdrawal, PDGFRalpha positive cells and gene expression showed significant increase in +ve control and T3-treated groups as compared to -ve control with insignificant difference in between the former two groups. After three weeks of cuprizone withdrawal, PDGFRalpha positive cells in T3-treated and +ve control groups decreased to the control levels. These results suggest that T3 was effective in improving remyelination when administered during acute phase and might direct progenitor lineage toward oligodendrocytes. PMID- 26993975 TI - Association of Hospital Prices for Coronary Artery Bypass Grafting With Hospital Quality and Reimbursement. AB - Although prices for medical services are known to vary markedly between hospitals, it remains unknown whether variation in hospital prices is explained by differences in hospital quality or reimbursement from major insurers. We obtained "out-of-pocket" price estimates for coronary artery bypass grafting (CABG) from a random sample of US hospitals for a hypothetical patient without medical insurance. We compared hospital CABG price to (1) "fair price" estimate from Healthcare Bluebook data using each hospital's zip code and (2) Society of Thoracic Surgeons composite CABG quality score and risk-adjusted mortality rate. Of 101 study hospitals, 53 (52.5%) were able to provide a complete price estimate for CABG. The mean price for CABG was $151,271 and ranged from $44,824 to $448,038. Except for geographic census region, which was weakly associated with price, hospital CABG price was not associated with other structural characteristics or CABG volume (p >0.10 for all). Likewise, there was no association between a hospital's price for CABG with average reimbursement from major insurers within the same zip code (rho = 0.07, p value = 0.6), Society of Thoracic Surgeoncomposite quality score (rho = 0.08, p value = 0.71), or risk adjusted CABG mortality (rho = -0.03 p value = 0.89). In conclusion, the price of CABG varied more than 10-fold across US hospitals. There was no correlation between price information obtained from hospitals and the average reimbursement from major insurers in the same market. We also found no evidence to suggest that hospitals that charge higher prices provide better quality of care. PMID- 26993974 TI - Impact of Percutaneous Coronary Intervention for Chronic Total Occlusion in Non Infarct-Related Arteries in Patients With Acute Myocardial Infarction (from the COREA-AMI Registry). AB - Chronic total occlusion (CTO) in a non-infarct-related artery (IRA) is an independent predictor of clinical outcomes in patients with acute myocardial infarction (AMI). This study evaluated the impact of successful percutaneous coronary intervention (PCI) for CTO of a non-IRA on the long-term clinical outcomes in patients with AMI. A total of 4,748 patients with AMI were consecutively enrolled in the Convergent Registry of Catholic and Chonnam University for AMI registry from January 2004 to December 2009. We enrolled 324 patients with CTO in a non-IRA. To adjust for baseline differences, propensity matching (96 matched pairs) was used to compare successful PCI and occluded CTO for the treatment of CTO in non-IRA. The primary clinical end points were all cause mortality and a composite of the major adverse cardiac events, including cardiac death, MI, stroke, and any revascularization during the 5-year follow-up. Patients who received successful PCI for CTO of non-IRA had lower rates of all cause mortality (16.7% vs 32.3%, hazard ratio 0.459, 95% CI 0.251 to 0.841, p = 0.012) and major adverse cardiac events (21.9% vs 55.2%, hazard ratio 0.311, 95% CI 0.187 to 0.516, p <0.001) compared with occluded CTO group. Subgroup analyses revealed that successful PCI resulted in a better mortality rate in patients with normal renal function compared to patients with chronic kidney disease (p = 0.010). In conclusion, successful PCI for CTO of non-IRA is associated with improved long-term clinical outcomes in patients with AMI. PMID- 26993976 TI - Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial). AB - Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF. PMID- 26993977 TI - Accuracy and Internal Consistency of Cardiac Magnetic Resonance Imaging in Measuring Branch Pulmonary Artery Flows in Patients With Conotruncal Anomalies and Branch Pulmonary Artery Stents. AB - Clinicians use branch pulmonary artery (BPA) blood flow distribution to help determine the need for intervention. Although phase-contrast magnetic resonance (PCMR) flow measurements are accurate, this has never been shown in the vicinity of a BPA ferromagnetic stent (FS) which produces significant susceptibility artifact. We retrospectively reviewed 49 consecutive PCMR studies performed from 2005 to 2012 on patients with repaired conotruncal anomalies and either left (n = 29) or right PA (n = 20) stents. Three methods of measuring the stented BPA flow were compared: (1) main PA (MPA) minus nonstented BPA, (2) direct PCMR of stented BPA away from the artifact, and (3) pulmonary venous flows (ipsilateral to stented BPA and derived pulmonary blood flow ratio from bilateral pulmonary venous flows). Internal consistency was tested with the Student t test, linear regression, Bland-Altman analysis, and intraclass correlation (ICC). The mean age was 11.7 +/- 6.9 years with 5.8 +/- 4.2 years between stent placement and CMR. There was good agreement without significant difference between MPA-derived stented BPA flow (method 1) and direct PCMR of stented BPA (method 2; 41 +/- 19% vs 39 +/- 19%, p = 0.59; R(2) = 0.84, p <0.001; ICC = 0.96). There was also good agreement between methods 1 and 2 compared to pulmonary venous flows, with the highest correlation occurring between method 2 and ipsilateral pulmonary venous flow (R(2) = 0.90, p <0.001; ICC = 0.97 for MPA-derived-stented BPA flow; R(2) = 0.94, p <0.001; ICC = 0.98 for direct PCMR of stented BPA). Eleven of the 49 patients (22%) underwent interventional catheterization after PCMR. In conclusion, in the vicinity of a BPA FS, accurate measurement of the net fractional pulmonary blood flow ratio is feasible. PCMR adjacent to the stent and ipsilateral pulmonary venous flows provide the most internally consistent data. These data underscore PCMR's utility in managing patients with implanted FS. PMID- 26993978 TI - Declining Incidence of Systolic Left Ventricular Dysfunction in Human Immunodeficiency Virus-Infected Individuals Treated With Highly Active Antiretroviral Therapy. PMID- 26993979 TI - Three-dimensional Doppler ultrasound findings in healthy wrist and finger tendon sheaths - can feeding vessels lead to misinterpretation in Doppler-detected tenosynovitis? AB - BACKGROUND: The aim was to investigate the presence of feeding vessels in or in close proximity to extensor and flexor tendon sheaths at the wrists level and in finger flexor tendon sheaths in healthy controls, using 3D ultrasound (US), which may cause pitfalls, in order to ensure correct interpretation of Doppler signals when diagnosing tenosynovitis. METHOD: Forty healthy participants (20 women and 20 men age 23-67 years) without prior history of arthritis, tendon diseases or present pain in their hands were included. Twenty participants had 3D Doppler US of the second and third finger and twenty of the right wrist. US was carried out using a GE Logiq E9 unit with a 3D US probe. The colour Doppler settings were to published recommendation. RESULTS: The feeding vessels in or in close proximity to the tendon sheaths were found in the flexor and extensor tendons sheaths at least once in each participant. No significant difference in feeding vessels was seen between the radial and carpal level in the wrist (p = 0.06) or between the second and third flexor tendon sheath (p = 0.84). CONCLUSION: Doppler findings in or in close proximity to the tendon sheaths were common in wrists and fingers in healthy participants. These feeding vessels can be a source of error, not only due to their presence but also because they may be interpreted as being inside the tendon sheath due to blooming and reverberations artefacts. These vessels should be taken into consideration when diagnosing Doppler tenosynovitis. PMID- 26993980 TI - Clinical results of conformal versus intensity-modulated radiotherapy using a focal simultaneous boost for muscle-invasive bladder cancer in elderly or medically unfit patients. AB - BACKGROUND: For elderly or medically unfit patients with muscle-invasive bladder cancer, cystectomy or chemotherapy are contraindicated. This leaves radical radiotherapy as the only treatment option. It was the aim of this study to retrospectively analyze the treatment outcome and associated toxicity of conformal versus intensity-modulated radiotherapy (IMRT) using a focal simultaneous tumor boost for muscle-invasive bladder cancer in patients not suitable for cystectomy. METHODS: One hundred eighteen patients with T2-4 N0-1 M0 bladder cancer were analyzed retrospectively. Median age was 80 years. Treatment consisted of either a conformal box technique or IMRT and included a simultaneous boost to the tumor. To enable an accurate boost delivery, fiducial markers were placed around the tumor. Patients were treated with 40 Gy in 20 fractions to the elective treatment volumes, and a daily tumor boost up to 55-60 Gy. RESULTS: Clinical complete response was seen in 87 % of patients. Three-year overall survival was 44 %, with a locoregional control rate of 73 % at 3 years. Toxicity was low, with late urinary and intestinal toxicity rates grade >= 2 of 14 and 5 %, respectively. The use of IMRT reduced late intestinal toxicity, whereas fiducial markers reduced acute urinary toxicity. CONCLUSIONS: Radical radiotherapy using a focal boost is feasible and effective for elderly or unfit patients, with a 3-year locoregional control of 73 %. Toxicity rates were low, and were reduced by the use of IMRT and fiducial markers. PMID- 26993982 TI - Generalized accelerated failure time spatial frailty model for arbitrarily censored data. AB - Flexible incorporation of both geographical patterning and risk effects in cancer survival models is becoming increasingly important, due in part to the recent availability of large cancer registries. Most spatial survival models stochastically order survival curves from different subpopulations. However, it is common for survival curves from two subpopulations to cross in epidemiological cancer studies and thus interpretable standard survival models can not be used without some modification. Common fixes are the inclusion of time-varying regression effects in the proportional hazards model or fully nonparametric modeling, either of which destroys any easy interpretability from the fitted model. To address this issue, we develop a generalized accelerated failure time model which allows stratification on continuous or categorical covariates, as well as providing per-variable tests for whether stratification is necessary via novel approximate Bayes factors. The model is interpretable in terms of how median survival changes and is able to capture crossing survival curves in the presence of spatial correlation. A detailed Markov chain Monte Carlo algorithm is presented for posterior inference and a freely available function frailtyGAFT is provided to fit the model in the R package spBayesSurv. We apply our approach to a subset of the prostate cancer data gathered for Louisiana by the surveillance, epidemiology, and end results program of the National Cancer Institute. PMID- 26993981 TI - Durability of Olyset campaign nets distributed between 2009 and 2011 in eight districts of Tanzania. AB - BACKGROUND: Long-lasting insecticidal nets (LLINs) are the first line choice for malaria vector control in sub-Saharan Africa, with most countries adopting universal coverage campaigns. However, there is only limited information on LLIN durability under user conditions. Therefore, this study aimed to assess the durability of Olyset((r)) LLINs distributed during campaigns between 2009 and 2011 in Tanzania. METHODS: A retrospective field survey was conducted in eight districts in Tanzania mainland to assess the durability of Olyset campaign nets. Household questionnaires were used to assess attrition, i.e. net loss. All nets remaining in households were collected. A sub-sample of 198 Olyset campaign nets was examined for bio-efficacy against Anopheles gambiae s.s. mosquitoes, permethrin content and physical integrity following standard World Health Organization (WHO) methods. RESULTS: Of 6067 campaign nets reported to have been received between 2009 and 2011, 35% (2145 nets) were no longer present. Most of those nets had been discarded (84%) mainly because they were too torn (94%). Of the 198 sub-sampled Olyset LLINs, 61% were still in serviceable physical condition sufficient to provide personal protection while 39% were in unserviceable physical condition according to WHO proportionate Hole Index (pHI). More than 96% (116/120) of nets in serviceable condition passed WHO bioefficacy criteria while all nets in unserviceable condition passed WHO bioefficacy criteria. Overall mean permethrin content was 16.5 g/kg (95% CI 16.2-16.9) with 78% of the sub-sampled nets retaining recommended permethrin content regardless of their age or physical condition. Nets aged 4 years and above had a mean permethrin content of 14 g/kg (95% CI 12.0-16.0). The only statistically significant predictor of reduced physical net integrity was rats in the house. CONCLUSIONS: Two-to-four years after a mass campaign, only 39% of distributed nets remain both present and in serviceable physical condition, a functional survival considerably below WHO assumptions of 50% survival of a 'three-year' net. However, the majority of nets still retained substantial levels of permethrin and could still be bio-chemically useful against mosquitoes if their holes were repaired, adding evidence to the value of net care and repair campaigns. PMID- 26993983 TI - Text mining for identifying topics in the literatures about adolescent substance use and depression. AB - BACKGROUND: Both adolescent substance use and adolescent depression are major public health problems, and have the tendency to co-occur. Thousands of articles on adolescent substance use or depression have been published. It is labor intensive and time consuming to extract huge amounts of information from the cumulated collections. Topic modeling offers a computational tool to find relevant topics by capturing meaningful structure among collections of documents. METHODS: In this study, a total of 17,723 abstracts from PubMed published from 2000 to 2014 on adolescent substance use and depression were downloaded as objects, and Latent Dirichlet allocation (LDA) was applied to perform text mining on the dataset. Word clouds were used to visually display the content of topics and demonstrate the distribution of vocabularies over each topic. RESULTS: The LDA topics recaptured the search keywords in PubMed, and further discovered relevant issues, such as intervention program, association links between adolescent substance use and adolescent depression, such as sexual experience and violence, and risk factors of adolescent substance use, such as family factors and peer networks. Using trend analysis to explore the dynamics of proportion of topics, we found that brain research was assessed as a hot issue by the coefficient of the trend test. CONCLUSIONS: Topic modeling has the ability to segregate a large collection of articles into distinct themes, and it could be used as a tool to understand the literature, not only by recapturing known facts but also by discovering other relevant topics. PMID- 26993984 TI - Dissipation of Pendimethalin in Soybean Crop Under Field Conditions. AB - Persistence of pendimethalin was studied in soil, soybean pods, straw and water under field conditions. Pendimethalin was applied at 1 and 2 kg a.i. ha(-1). Residues in soil were detected up to 60 and 90 days at the recommended and double dose, respectively. Dissipation followed first order kinetics and was accounted for by a biphasic pattern. The half-life for the initial phase and later phase was 12.73 and 26.60 days, respectively, for recommended and 7.25 and 37.91 days, respectively, for double dose. The limit of quantification was 0.005 ug g(-1) of sample. Percent recovery from soil, oil, defatted cake, straw and water samples fortified with 0.01-1.0 mg kg(-1) varied from 84.5 %-89.6 %, 84.6 %-88.7 %, 79.4 %-86.0 %, 78.2 %-85.6 % and 90.2 %-93.0 %, respectively. At harvest, pendimethalin residue in soybean pods, straw, and soil were below detectable limits. No residues of pendimethalin were detected in ground water. Current application of pendimethalin in the environment is not expected to cause adverse health effects form the consumption of soybeans. PMID- 26993985 TI - Myelodysplastic Syndrome and Acute Lymphocytic Leukemia in Common Variable Immunodeficiency (CVID). PMID- 26993987 TI - Is the Guideline Already Out of Date? PMID- 26993986 TI - Next Generation Sequencing Data Analysis in Primary Immunodeficiency Disorders - Future Directions. AB - Primary immunodeficiency diseases (PIDs) comprise a group of highly heterogeneous immune system diseases and around 300 forms of PID have been described to date. Next Generation Sequencing (NGS) has recently become an increasingly used approach for gene identification and molecular diagnosis of human diseases. Herein we summarize the practical considerations for the interpretation of NGS data and the techniques for searching disease-related PID genes, and suggest future directions for research in this field. PMID- 26993988 TI - Global Leadership Conversation: Addressing Malnutrition. PMID- 26993989 TI - A Comparison of Fish Oil Sources for Parenteral Lipid Emulsions in a Murine Model. AB - BACKGROUND: Fat emulsions are important components of parenteral nutrition (PN). Fish oil (FO) emulsions reverse cholestasis in PN-associated liver disease. There are 2 FO monographs. One is "FO; rich in omega-3 fatty acids" (NFO). The other, "omega-3 acids," (PFO), is enriched in omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The purpose of this study is to compare the effects of 20% NFO and PFO emulsions produced in the laboratory in a murine model. METHODS: Emulsions were compounded containing different oils: soybean oil (SO), NFO, and two PFOs differing in percentage of fatty acids as triglycerides (PFO66 and PFO90). Chow-fed mice received saline, one of the above emulsions, or a commercial FO (OM) intravenously (2.4 g/kg/day) for 19 days. On day 19, animals were euthanized. Livers, spleens, and lungs were procured for histologic analysis. RESULTS: OM, SO, NFO, and PFO90 were well tolerated clinically. PFO66 resulted in tachypnea and lethargy for ~1 minute following injections. At euthanasia, PFO66 and PFO90 groups had organomegaly. Histologically, these groups had splenic and hepatic fat-laden macrophages, and lungs had scattered fat deposits. Other groups had normal organs. CONCLUSIONS: PFO emulsions present an attractive possibility for improving inflammation in PN dependent patients by concentrating anti-inflammatory EPA and DHA. However, 20% PFO emulsions were poorly tolerated and precipitated adverse end organ sequelae, suggesting that they may not be safe. Development of novel manufacturing methods may achieve safe 20% PFO parenteral emulsions, but by established formulation methods, these emulsions were clinically suboptimal despite meeting pharmacopeial standards. PMID- 26993990 TI - The patient satisfaction questionnaire of EUprimecare project: measurement properties. AB - OBJECTIVE: The measurement of patient satisfaction is considered an essential outcome indicator to evaluate health care quality. Patient satisfaction is considered a multi-dimensional construct, which would include a variety of domains. Although a large number of studies have proposed scales to measure patient satisfaction, there is a lack of psychometric information on them. This study aims to describe the psychometric properties of the Primary Care Satisfaction Scale (PCSS) of the EUprimecare project. DESIGN: A cross-sectional survey of patient satisfaction with primary care was carried out by telephone interview. SETTING: Primary care services of Estonia, Finland, Germany, Hungary, Lithuania, Italy and Spain. PARTICIPANTS: A total of 3020 adult patients aged 18 65 years old attending primary care services. METHOD: Classic psychometric properties were analysed and Rasch analysis was used to assess the following measurement properties: fit to the Rasch model; uni-dimensionality; reliability; differential item functioning (DIF) by gender, age, civil status, area of residency and country; local independency; adequacy of response scale; and scale targeting. RESULTS: To achieve good fit to the Rasch model, the original response scales of three items (1, 2 and 6) were rescored and Item 3 (waiting time in the room) was removed. The scale was uni-dimensional and Person Separation Index was 0.79, indicating a good reliability. All items were free from bias. PCSS linear measure displayed satisfactory convergent validity with overall satisfaction with primary care. CONCLUSIONS: PCSS, as a reliable and valid scale, could be used to measure patient satisfaction in primary care in Europe. PMID- 26993991 TI - On dewetting of thin films due to crystallization (crystallization dewetting). AB - Drying and crystallization of a thin liquid film of an ionic or a similar solution can cause dewetting in the resulting thin solid film. This paper aims at investigating this type of dewetting, herein termed "crystallization dewetting", using PbI2 dissolved in organic solvents as the model solution. PbI2 solid films are usually used in X-ray detection and lead halide perovskite solar cells. In this work, PbI2 films are fabricated using spin coating and the effect of major parameters influencing the crystallization dewetting, including the type of the solvent, solution concentration, drying temperature, spin speed, as well as imposed vibration on the substrate are studied on dewetting, surface profile and coverage, using confocal scanning laser microscopy. Simplified hydrodynamic governing equations of crystallization in thin films are presented and using a mathematical representation of the process, it is phenomenologically demonstrated that crystallization dewetting occurs due to the absorption and consumption of the solution surrounding a growing crystal. Among the results, it is found that a low spin speed (high thickness), a high solution concentration and a low drying temperature promote crystal growth, and therefore crystallization dewetting. It is also shown that imposed vibration on the substrate can affect the crystal size and crystallization dewetting. PMID- 26993992 TI - Relaxation rate of the shape fluctuation of a fluid membrane immersed in a near critical binary fluid mixture. AB - We consider the two-time correlation of the shape fluctuation of a fluid membrane immersed in a near-critical binary fluid mixture. Usually one component of the mixture is preferably attracted by the membrane. Adsorption layers, where the preferred component is more concentrated, are generated on both sides of the membrane significantly because of the near-criticality. The resultant gradient of the local mass-density difference between the two components generates additional stress, including the osmotic pressure, to influence the membrane motion. Assuming the mixture to be in the homogeneous phase near, but not too close to, the demixing critical point, we use the Gaussian free-energy functional to calculate the relaxation rate for a wavelength much longer than the correlation length of the mixture. Our calculation supposes weak preferential attraction and weak dependence of the mixture viscosity on the mass-density difference, and is performed within the linear approximation with respect to the undulation amplitude. It is shown for small wave number that the additional stress makes the relaxation more rapid independently of whether the preferred component is more viscous or not and that the relaxation rate can be regarded as proportional to the wave number even for a tensionless membrane. This linear dependence comes from the balance between the frictional force due to the mixture viscosity and the restoring force of the adsorption layer. PMID- 26993993 TI - Internal tension in a collapsed polymer under shear flow and the connection to enzymatic cleavage of von Willebrand factor. AB - By means of Brownian hydrodynamics simulations we show that the tension distribution along the contour of a single collapsed polymer in shear flow is inhomogeneous and above a threshold shear rate exhibits a double-peak structure when hydrodynamic interactions are taken into account. We argue that the tension maxima close to the termini of the polymer chain reflect the presence of polymeric protrusions. We establish the connection to shear-induced globule unfolding and determine the scaling behavior of the maximal tensile forces and the average protrusion length as a function of shear rate, globule size, and cohesive strength. A quasi-equilibrium theory is employed in order to describe the simulation results. Our results are used to explain experimental data for the shear-sensitive enzymatic degradation of von Willebrand factor. PMID- 26993995 TI - The Effect of Different Metabolic Syndrome: Definitions on the Relationship Between Metabolic Syndrome and LUTS in Men With Benign Prostatic Enlargement. AB - Because various criteria are used to define metabolic syndrome (MetS), this study examines the most relevant definition for patients with benign prostatic enlargement (BPE). Most studies regarding the link between MetS and BPE/lower urinary tract symptoms (LUTS) have used the National Cholesterol Education Program Adult Treatment Panel III criteria for diagnosis, while a few have used criteria from the International Diabetes Federation and/or American Heart Association. Patients with LUTS due to BPE are classified as having MetS or not by the aforementioned three definitions. Prostate volume, International Prostate Symptom Score, storage and voiding subscores, maximum urinary flow rate, and the postvoid urine of patients with and without MetS were compared separately in the three different groups. Surgical and medical treatment prevalence was also compared between three groups. No matter which definition was used, the International Prostate Symptom Score, the storage and voiding symptom scores, prostate volume, prostate-specific antigen, and postvoid urine were significantly higher in the patients with MetS. The maximum urinary flow rate was similar between patients with and without MetS, according to all three different definitions. There was no significant difference in the aforementioned parameter between patients with MetS diagnosed with the three different definitions. Irrespective of which definition was used, the surgical treatment rate was not significantly different in patients diagnosed with than without MetS, or between the patients with MetS diagnosed with the three different definitions. The authors suggest that it does not matter which of the aforementioned three definitions is used during the evaluation of MetS in men with BPE/LUTS. PMID- 26993994 TI - Gender-Related Differences in Heart Rate Variability of Epileptic Patients. AB - Recently, heart rate variability (HRV) analysis has been used as an indicator of epileptic seizures. As women have a lower sudden, unexpected death in epilepsy risk and greater longevity than men, the authors postulated that there are significant gender-related differences in heart rate dynamics of epileptic patients. The authors analyzed HRV during 5-minute segments of continuous electrocardiogram recording of age-matched populations. The middle-aged epileptic patients included males ( n = 12) and females ( n = 12), ranging from 41 to 65 years of age. Relatively high- (0.15 Hz-0.40 Hz) and low-frequency (0.01 Hz-0.15 Hz) components of HRV were computed using spectral analysis. Poincare parameters of each heart rate time series were considered as nonlinear features. The mean heart rate markedly differed between gender groups including both right- and left sided seizures. High-frequency heart rate power and the low-frequency/high frequency ratio increased in the pre-ictal phase of both male and female groups ( p < .01), but men showed more increase especially in right-sided seizures. The standard deviation ratio, SD2/ SD1, of pre-ictal phase was greater in males than females ( p < .01). High-frequency spectral power and parasympathetic activity were higher in the female group with both right- and left-sided seizures. Men showed a sudden increase in sympathetic activity in the pre-ictal phase, which might increase the risk of cardiovascular disease in comparison to women. These complementary findings indicate the need to account for gender, as well as localization in HRV analysis. PMID- 26993996 TI - Health Information Behavior of Expectant and Recent Fathers. AB - Given the importance of paternal involvement in maternal and child health, the current investigation takes a closer look at expectant and recent (E/R) fathers' health information behavior during pregnancy, childbirth, and child care. A total of 186 E/R fathers (68 low-income) completed a survey gauging information needs, sources of information, and information-seeking behavior. Results are summarized in four statements that may help low-income E/R fathers get the information they need during a partner's pregnancy or after a child is born: (a) paternal information needs are diverse, (b) information needs change across stages of child development, PMID- 26993997 TI - The Consideration of Socioeconomic Determinants in Prevention of Traditional Male Circumcision Deaths and Complications. AB - The responsiveness to socioeconomic determinants is perceived as highly crucial in preventing the high mortality and morbidity rates of traditional male circumcision initiates in the Eastern Cape, a province in South Africa. The study sought to describe social determinants and explore economic determinants related to traditional circumcision of boys from 12 to 18 years of age in Libode rural communities in Eastern Cape Province. From the results of a descriptive cross sectional survey ( n = 1,036), 956 (92.2%) boys preferred traditional male circumcision because of associated social determinants which included the variables for the attainment of social manhood values and benefits; 403 (38.9%) wanted to attain community respect; 347 (33.5%) wanted the accepted traditional male circumcision for hygienic purposes. The findings from the exploratory focus group discussions were revolving around variables associated with poverty, unemployment, and illegal actions to gain money. The three negative economic determinants were yielded as themes: (a) commercialization and profitmaking, (b) poverty and unemployment, (c) taking health risk for cheaper practices, and the last theme was the (d) actions suggested to prevent the problem. The study concluded with discussion and recommendations based on a developed strategic circumcision health promotion program which is considerate of socioeconomic determinants. PMID- 26993998 TI - Conflict in Men's Experiences With Antidepressants. AB - While men's experiences of depression and help seeking are known to be shaped by gender, there is little research which examines their experience of using antidepressants to treat this. This study is based on in-depth, narrative-style interviews with 20 New Zealand men who had used antidepressants. The analysis identified a number of areas of conflict in the men's accounts of using this medication. Conflict centered on the way taking antidepressants was seen as undermining personal control while also allowing users to take charge of their problems; facilitating general functioning while undermining sexual functioning; relieving emotional distress while undermining emotional vitality; and the tension participants felt between making autonomous judgments about the value of antidepressants and relying on the "expertise" of others. Participants negotiated these conflicts in a variety of ways. In some cases, antidepressants were positioned as being able to affirm aspects of traditional masculinity, while a smaller number of participants managed these conflicts by redefining aspects of their own masculinity in ways that contrasted with dominant constructions. This research is limited by the sample of older, more privileged men in the context of New Zealand culture which favors macho forms of masculinity. In similar contexts, mental health practitioners should be mindful of the conflicts that men might experience in relation to their antidepressant use. Facilitating men's exploration of these issues may enable them to make better decisions about treatment options or to provide more effective support to those who have opted for antidepressant treatment. PMID- 26994000 TI - Mentoring perception and academic performance: an Academic Health Science Centre survey. AB - PURPOSE: To determine the association between professors' self-perception of mentoring skills and their academic performance. DESIGN: Two hundred and fifteen professors from Imperial College London, the first Academic Health Science Centre (AHSC) in the UK, were surveyed. The instrument adopted was the Mentorship Skills Self-Assessment Survey. Statement scores were aggregated to provide a score for each shared core, mentor-specific and mentee-specific skill. Univariate and multivariate regression analyses were used to evaluate their relationship with quantitative measures of academic performance (publications, citations and h index). RESULTS: There were 104 professors that responded (response rate 48%). There were no statistically significant negative correlations between any mentoring statement and any performance measure. In contrast, several mentoring survey items were positively correlated with academic performance. The total survey score for frequency of application of mentoring skills had a statistically significant positive association with number of publications (B=0.012, SE=0.004, p=0.006), as did the frequency of acquiring mentors with number of citations (B=1.572, SE=0.702, p=0.030). Building trust and managing risks had a statistically significant positive association with h-index (B=0.941, SE=0.460, p=0.047 and B=0.613, SE=0.287, p=0.038, respectively). CONCLUSIONS: This study supports the view that mentoring is associated with high academic performance. Importantly, it suggests that frequent use of mentoring skills and quality of mentoring have positive effects on academic performance. Formal mentoring programmes should be considered a fundamental part of all AHSCs' configuration. PMID- 26993999 TI - Beliefs Regarding Prostate Cancer Screening Among Black Males Aged 18 to 40 Years. AB - This study was conducted to identify the salient behavioral beliefs of young Black men toward prostate cancer screening, and to identify the issues surrounding their comfortability with prostate examinations. A total of 20 Black men, aged between 18 and 40 years, participated in three focus group sessions between June 2013 and July 2013 in Austin, Texas. Participants were asked open ended questions about: (a) the advantages and disadvantages of screening to identify salient behavioral beliefs about screening and (b) issues that would make prostate examinations comfortable or uncomfortable to identify comfortability factors. Focus group discussions were tape-recorded, transcribed, and content analyzed to identify emerging themes of salient beliefs and comfortability. Also, nine salient behavioral beliefs toward prostate cancer screening were identified, and eight factors were linked to comfortability with prostate examinations. Given the increase of prostate cancer disparity as a public health issue, understanding the beliefs of Black men of prescreening age (18-40 years) may be crucial to the effectiveness of future interventions to improve screening when recommended at later ages. PMID- 26994001 TI - Saving the starfish: World Federation of Pediatric Imaging (WFPI) development, work to date, and membership feedback on international outreach. PMID- 26994002 TI - pAKT Expression and Response to Sorafenib in Differentiated Thyroid Cancer. AB - Sorafenib has an antitumor activity in patients with radioactive iodine refractory differentiated thyroid carcinoma (RAIR-DTC). Prior research has implicated signaling through the MAPK and AKT/PI3K pathways in the progression of DTC. To assess whether the activity of these pathways is predictive of response to sorafenib, we retrospectively studied molecular tumor markers from these two pathways from a phase 2 study of sorafenib in RAIR-DTC. Tumor samples from 40 of 53 DTC subjects obtained prior to initiation of sorafenib were immunostained with DAB-labeled antibodies to phospho-AKT (pAKT), phospho-ERK (pERK), and phospho-S6 (pS6). BRAFV600E genetic mutation analysis was performed on all samples. Expression levels and mutational status were compared to response and progression free survival (PFS) for each patient. Low tumor expression of nuclear pAKT was associated with partial response to sorafenib (p < 0.01). Patients with nuclear pAKT expression that was below the median for our sample were more than three times as likely to have a partial response as patients with equal to or above median expression. There was no correlation between tumor expression of nuclear pERK or pS6 and response. Endothelial cell and pericyte expression of pERK, pAKT, and pS6 were not predictive of response. There was no correlation between BRAFV600E mutation status and partial response. No correlation was observed between either the expression of pAKT, pERK, or pS6, or the presence of the BRAFV600E mutation, and PFS. In conclusion, lower tumor expression of nuclear pAKT was associated with higher rate of response to sorafenib. This observation justifies evaluation of combination therapy with sorafenib and an inhibitor of the PI3K/AKT signaling pathway in RAIR-DTC. PMID- 26994003 TI - Erratum to: Efficacy and Safety Study of Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized, Double-Blind, Multicenter Trial. PMID- 26994004 TI - Sister chromatid separation and monopolar spindle organization in the first meiosis as two mechanisms of unreduced gametes formation in wheat-rye hybrids. AB - KEY MESSAGE: Unreduced gametes. The absence of a strict pachytene checkpoint in plants presents an opportunity to study meiosis in polyhaploid organisms. In the present study, we demonstrate that meiosis is coordinated in hybrids between disomic wheat-rye substitution lines 1Rv(1A), 2R(2D), 5R(5D), 6R(6A) and rye (Triticum aestivum L. * Secale cereale L., 4x = 28, ABDR). By using in situ hybridization with a centromere pAet6-09 probe and immunostaining with H3Ser10ph , CENH3-, and alpha-tubulin-specific antibodies, we distinguished four chromosome behaviour types. The first one is a mitotic-like division that is characterized by mitotic centromere architecture, robust bipolar spindle, one-step loss of arm and centromere cohesion, and sister chromatid separation in the first and only meiotic division. The second type involves a monopolar spindle formation, which appears as a hat-shaped group of chromosomes moving in one direction, wherein MT bundles are co-oriented polewards. It prevents chromosome segregation in meiosis I, with a bipolar spindle distributing sister chromatids to the poles in meiosis II. These events subsequently result in the formation of unreduced microspores. The other two meiotic-like chromosome segregation patterns known as reductional and equational plus reductional represent stand-alone types of cell division rather than intermediate steps of meiosis I. Only sterile pollen is produced as a result of such meiotic-like chromosome behaviours. Slightly variable meiotic phenotypes are reproducibly observed in hybrids under different growth conditions. The 2R(2D)xR genotype tends to promote reductional division. In contrast, the genotypes 1Rv(1A)xR, 5R(5D)xR, and 6R(6A)xR promote equational chromosome segregation and monopolar spindle formation in addition to reductional and equational plus reductional division types. PMID- 26994005 TI - Total and bone-specific alkaline phosphatase are associated with bone mineral density over time in end-stage renal disease patients starting dialysis. AB - BACKGROUND: Alkaline phosphatase (ALP) and bone-specific ALP (BALP) are implicated in the abnormal skeletal mineralization and accelerated vascular calcification in chronic kidney disease (CKD) patients. Whereas ALP and BALP may predict mortality in CKD, BALP is reported to have higher sensitivity and specificity than total ALP in reflecting histological alterations in bone; however, results on their associations with bone mineral density (BMD) are inconsistent. Here we evaluated associations of total ALP and BALP with BMD during up to 24 months in end-stage renal disease (ESRD) patients. METHODS: In this longitudinal study, 194 ESRD patients (median age 57 years, 66 % male, 32 % diabetes mellitus, mean body mass index 24.8 kg/m2) underwent measurements of total ALP and BALP and total and regional body BMD (by dual-energy X-ray absorptiometry) at dialysis initiation (n = 194), and after 12 (n = 98) and 24 months (n = 40) on dialysis. RESULTS: At baseline, patients had median total ALP 65.4 (43.3-126.4) U/l, BALP 13.5 (7.1-27.3) ug/l and BMD 1.14 (0.97-1.31) g/cm2. During the study period, serum concentrations of ALP and BALP increased significantly (p < 0.001), whereas total and regional BMD remained stable. BMD correlated inversely with total ALP (rho = -0.20, p = 0.005) and BALP (rho = 0.30, p < 0.001) at baseline, and correlations were similar also at 12 and 24 months. CONCLUSION: ALP and BALP are equally accurate albeit weak predictors of BMD in ESRD patients, both at baseline and longitudinally. The dissociation between stable BMD and increasing ALP and BALP may possibly reflect increased soft tissue calcifications with time on dialysis. PMID- 26994006 TI - Feed-forward active contour analysis for improved brachial artery reactivity testing. AB - The object of this study was to utilize a novel feed-forward active contour (FFAC) algorithm to find a reproducible technique for analysis of brachial artery reactivity. Flow-mediated dilation (FMD) is an important marker of vascular endothelial function but has not been adopted for widespread clinical use given its technical limitations, including inter-observer variability and differences in technique across clinical sites. We developed a novel FFAC algorithm with the goal of validating a more reliable standard. Forty-six healthy volunteers underwent FMD measurement according to the standard technique. Ultrasound videos lasting 5-10 seconds each were obtained pre-cuff inflation and at minutes 1 through 5 post-cuff deflation in longitudinal and transverse views. Automated segmentation using the FFAC algorithm with initial boundary definition from three different observers was used to analyze the images to measure diameter/cross sectional area over the cardiac cycle. The %FMD was calculated for average, minimum, and maximum diameters/areas. Using the FFAC algorithm, the population specific coefficient of variation (CV) at end-diastole was 3.24% for transverse compared to 9.96% for longitudinal measurements; the subject-specific CV was 15.03% compared to 57.41%, respectively. For longitudinal measurements made via the conventional method, the population-specific CV was 4.77% and subject specific CV was 117.79%. The intraclass correlation coefficient (ICC) for transverse measurements was 0.97 (95% CI: 0.95-0.98) compared to 0.90 (95% CI: 0.84-0.94) for longitudinal measurements with FFAC and 0.72 (95% CI: 0.51-0.84) for conventional measurements. In conclusion, transverse views using the novel FFAC method provide less inter-observer variability than traditional longitudinal views. Improved reproducibility may allow adoption of FMD testing in a clinical setting. The FFAC algorithm is a robust technique that should be evaluated further for its ability to replace the more limited conventional technique for measurement of FMD. PMID- 26994007 TI - Outcomes of accelerated catheter-directed thrombolysis in patients with acute arterial thrombosis. AB - Current intra-arterial catheter-directed thrombolysis (CDT) protocols recommend treatment with small doses of a thrombolytic agent, which excludes patients in need of urgent revascularization. We evaluated the effects of accelerated thrombolysis utilizing increased recombinant tissue plasminogen activator (rt-PA) doses. Forty-one patients with acute, thrombotic limb ischemia (ALI) were treated using accelerated CDT. The treatment consisted of an initial dose of 10 mg rt-PA for 30 minutes followed by a 3-hour course of a continuous intra-arterial 10 mg/hour rt-PA infusion. Simultaneously, intravenous unfractionated heparin (500 IU/hour) was administered. No deaths occurred. Satisfactory lysis was achieved in 37 of the 41 patients (90.2%). All significant underlying lesions were corrected (89.2%). Complications developed in nine patients (22%); the most frequent complication (four patients, 9.8%) was puncture site hematoma. The reintervention rate was 2.6% and 15.4% at the 1 and 6-month follow-ups, respectively. The major amputation rate was 10.3% and 12.8% at the 1 and 6-month follow-ups, respectively. Outflow compromise was adversely related to successful outcome at the 6-month follow-up (p=0.01). In conclusion, this study confirms the effectiveness and safety of the accelerated CDT regimen for treatment of thrombotic ALI at a single center, but requires confirmation in further studies. PMID- 26994008 TI - Congenital iliac malformation and endovascular treatment of lower limb ischemia. PMID- 26994009 TI - Abnormalities of the bone marrow immune microenvironment in patients with immune thrombocytopenia. AB - Immune thrombocytopenia (ITP) is an acquired autoimmune disease. Although antiplatelet antibodies are considered as the primary immunologic defect in these patients, dysfunctional cellular immunity is also important in the pathophysiology of ITP. Peripheral T cell abnormalities have been demonstrated in patients with ITP; however, whether the impaired bone marrow (BM) microenvironment, specifically the BM immune microenvironment, is involved in the pathogenesis of ITP remains unknown. In this study, the compartments of the BM immune microenvironment and BM vascular microenvironment were analyzed in 26 untreated patients with ITP and 26 healthy donors (HD). Subsets of T cells in the BM immune microenvironment, including Th1, Th2, Tc1, Tc2, Th17, and Treg cells, were analyzed via flow cytometry. BM endothelial cells and perivascular cells, which are key elements of the vascular microenvironment, were analyzed via flow cytometry as well as hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining in situ. Elements of the BM vascular microenvironment were found to be normal in patients with ITP, but abnormal characteristics of the BM immune microenvironment, including excessive polarization in Th1, Tc1, and Th17 cells and a remarkable decrease in Treg cells, were observed in patients with ITP. Therefore, a deregulated T cell response in the BM microenvironment might play an important role in the pathogenesis of ITP. PMID- 26994010 TI - Splenic irradiation before hematopoietic stem cell transplantation for chronic myeloid leukemia: long-term follow-up of a prospective randomized study. AB - In the context of discussions on the reproducibility of clinical studies, we reanalyzed a prospective randomized study on the role of splenic irradiation as adjunct to the conditioning for hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Between 1986 and 1989, a total of 229 patients with CML were randomized; of these, 225 (98 %; 112 with, 113 without splenic irradiation) could be identified in the database and their survival updated. Results confirmed the early findings with no significant differences in all measured endpoints (overall survival at 25 years: 42.7 %, 32.0-52.4 % vs 52.9 %, 43.2-62.6 %; p = 0.355, log rank test). Additional splenic irradiation failed to reduce relapse incidence. It did not increase non-relapse mortality nor the risk of late secondary malignancies. Comforting are the long-term results from this predefined consecutive cohort of patients: more than 60 % were alive at plus 25 years when they were transplanted with a low European Society for Blood and Marrow Transplantation (EBMT) risk sore. This needs to be considered today when treatment options are discussed for patients who failed initial tyrosine kinase inhibitor therapy and have an available low risk HLA-identical donor. PMID- 26994011 TI - Practical method for determination of air kerma by use of an ionization chamber toward construction of a secondary X-ray field to be used in clinical examination rooms. AB - We propose a new practical method for the construction of an accurate secondary X ray field using medical diagnostic X-ray equipment. For accurate measurement of the air kerma of an X-ray field, it is important to reduce and evaluate the contamination rate of scattered X-rays. To determine the rate quantitatively, we performed the following studies. First, we developed a shield box in which an ionization chamber could be set at an inner of the box to prevent detection of the X-rays scattered from the air. In addition, we made collimator plates which were placed near the X-ray source for estimation of the contamination rate by scattered X-rays from the movable diaphragm which is a component of the X-ray equipment. Then, we measured the exposure dose while changing the collimator plates, which had diameters of 25-90 mm(phi). The ideal value of the exposure dose was derived mathematically by extrapolation to 0 mm(phi). Tube voltages ranged from 40 to 130 kV. Under these irradiation conditions, we analyzed the contamination rate by the scattered X-rays. We found that the contamination rates were less than 1.7 and 2.3 %, caused by air and the movable diaphragm, respectively. The extrapolated value of the exposure dose has been determined to have an uncertainty of 0.7 %. The ionization chamber used in this study was calibrated with an accuracy of 5 %. Using this kind of ionization chamber, we can construct a secondary X-ray field with an uncertainty of 5 %. PMID- 26994012 TI - Simultaneous ventriculoperitoneal shunt removal and endoscopic third ventriculostomy for three patients previously treated for intracranial germ cell tumors more than 20 years ago. AB - BACKGROUND: Obstructive hydrocephalus is the most common complication of intracranial germ cell tumors (IGCTs). Although ventriculoperitoneal shunts (VPSs) were previously used for treating this condition, they have recently been replaced by endoscopic third ventriculostomy (ETV), as the latter can avoid various complications caused by a VPS and can preserve physiological cerebrospinal fluid (CSF) dynamics. Therefore, if a VPS malfunctioned in patients who had previously been treated for IGCTs, it seems reasonable to consider removing the problematic VPS, followed by ETV, as long as magnetic resonance imaging reveals third ventricle floor ballooning and the cause of obstruction in the ventricular system, which are indicators for ETV. CASE PRESENTATION AND DISCUSSION: Here, we present the cases of three patients who underwent simultaneous removal of malfunctioning VPSs and ETV, more than 20 years (range 20 27 years) after initial treatment for IGCT and relevant obstructive hydrocephalus. Despite a relatively long shunt dependency, their obstructive hydrocephalus was well-managed by ETV, probably because CSF absorptive capacity remained intact after IGCT ablation by radio-chemotherapy. CONCLUSION: Patients with previously treated IGCTs can thus be released from the need for a VPS, regardless of long-term shunt dependency. PMID- 26994013 TI - Traumatic basal ganglia hematoma following closed head injuries in children. AB - PURPOSE: High-velocity trauma with acceleration/deceleration forces turns into shear stress over lenticulostriate or anterior choroidal arteries that lead to basal ganglia hemorrhage. Traumatic basal ganglia hematoma has rarely been described in pediatric population. The aim of this study was to present our clinical series of pediatric patients with traumatic basal ganglia hematoma and to analyze the prognostic indicators of traumatic basal ganglia hematoma. METHODS: In this retrospective case series, emergency admissions of pediatric patients with traumatic basal ganglia hematoma due to closed head injury were analyzed. Demographic, clinical, and radiographical data of the patients were retrieved from patients' charts and picture archiving and communication system. RESULTS: There were four children with traumatic basal ganglia hematoma (TBGH). All patients were male. Median age was 8 years (range = 7-16 years). Road accident (three) and fall (one) were the causes of the traumas. Basal ganglia hematoma was present on the right side in one patient and on the left side in three patients. Hematoma volumes ranged from 0.9 to 8.94 ml. All patients were treated conservatively. One patient recovered fully; two patients were moderately disabled at their last clinical follow-ups. The last patient with diffuse subarachnoidal hemorrhage and edema died despite all interventions. CONCLUSIONS: Traumatic basal ganglia hematomas are unique and different from other kind of intracerebral hematomas. The eloquent nature of basal ganglia makes it more vulnerable to head trauma. Mechanism of injury, energy and velocity of injury are the most important prognostic criteria. Post-traumatic phase of injury should be carefully observed in patients with TBGH, especially when mechanism and velocity of injury are severe and high. PMID- 26994014 TI - A phase 1 clinical trial of ASG-5ME, a novel drug-antibody conjugate targeting SLC44A4, in patients with advanced pancreatic and gastric cancers. AB - Purpose ASG-5ME is an antibody-drug conjugate (ADC) targeting SLC44A4, a novel cell surface target expressed on most pancreatic and gastric cancers. This first in-human study of ASG-5ME evaluated safety, pharmacokinetics, and preliminary activity of ASG-5ME in advanced pancreatic and gastric cancer patients. Experimental Design This phase 1, dose-escalation, multicenter study determined the maximum tolerated dose (MTD) and assessed safety and antitumor activity. The dose-escalation portion enrolled metastatic pancreatic adenocarcinoma patients; gastric adenocarcinoma patients were included in the dose-expansion portion. Patients received ASG-5ME intravenously on Days 1, 8, and 15 of 28-day cycles. Results Thirty-five pancreatic cancer patients (median age 63 years; performance status 0 [40 %] or 1 [60 %]) were treated at doses of 0.3 to 1.5 mg/kg (median duration 8.1 weeks). The MTD was exceeded at 1.5 mg/kg (n = 7) with 1 dose limiting toxicity (DLT) of Grade 4 gastrointestinal hemorrhage. Four patients experienced non-DLT Grade 3 or 4 neutropenia. Fifteen gastric cancer patients (median age 59 years; performance status 0 [33 %] or 1 [67 %]) were treated at the identified MTD of 1.2 mg/kg (median duration 8.7 weeks). Common drug-related adverse events included fatigue (29 %), nausea (23 %), and vomiting (23 %) for pancreatic cancer patients and fatigue (33 %) and decreased appetite (33 %) for gastric cancer patients. Best clinical response was 1 partial response in each cohort. Disease-control rates of 33 % (pancreatic) and 47 % (gastric) were observed at the MTD. All patient biopsies (23 pancreatic, 15 gastric) expressed the SLC44A4 antigen. Conclusions ASG-5ME treatment was generally well tolerated with limited evidence of antitumor activity. PMID- 26994015 TI - Catalytic upgrading of butyric acid towards fine chemicals and biofuels. AB - Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals and biofuels. Here, current chemocatalytic and biocatalytic conversion methods are reviewed with a focus on upgrading butyric acid to 1-butanol or butyl butyrate. Supported Ruthenium- and Platinum-based catalyst and lipase exhibit important activities which can pave the way for more sustainable process concepts for the production of green fuels and chemicals. PMID- 26994016 TI - Response functions for electrically coupled neuronal network: a method of local point matching and its applications. AB - Neuronal networks connected by electrical synapses, also referred to as gap junctions, are present throughout the entire central nervous system. Many instances of gap-junctional coupling are formed between dendritic arbours of individual cells, and these dendro-dendritic gap junctions are known to play an important role in mediating various brain rhythms in both normal and pathological states. The dynamics of such neuronal networks modelled by passive or quasi active (resonant) membranes can be described by the Green's function which provides the fundamental input-output relationships of the entire network. One of the methods for calculating this response function is the so-called 'sum-over trips' framework which enables the construction of the Green's function for an arbitrary network as a convergent infinite series solution. Here we propose an alternative and computationally efficient approach for constructing the Green's functions on dendro-dendritic gap junction-coupled neuronal networks which avoids any infinite terms in the solutions. Instead, the Green's function is constructed from the solution of a system of linear algebraic equations. We apply this new method to a number of systems including a simple single cell model and two-cell neuronal networks. We also demonstrate that the application of this novel approach allows one to reduce a model with complex dendritic formations to an equivalent model with a much simpler morphological structure. PMID- 26994017 TI - Dermoscopic features of aquagenic syringeal acrokeratoderma. PMID- 26994018 TI - Solvent effect on molecular structure, IR spectra, thermodynamic properties and chemical stability of zoledronic acid: DFT study. AB - Zoledronic acid (ZL) has been used widely for treating skeletal diseases because of its high potency in inhibiting bone resorption. A detailed understanding of its physicochemical characteristics may be of great significance in both medicinal chemistry and structural biology for the design of novel bisphosphonates with higher activity. In the present work, the monoclinic (IM) and triclinic (IT) polymorphs of ZL in the gas phase and the aqueous phase were studied by density functional theory (DFT) method at the B3LYP/6-311++G** level. The polarizable continuum model (PCM) was employed to study the solvent effect on structures and properties. The optimized IM and IT conformations in both phases are in reasonable agreement with the experimental structures with the overall mean absolute percent deviation (MAPD%) less than 3.1 %. The presence of intramolecular hydrogen bond within both conformations was identified in the solvent. The IR spectra were simulated and assigned in detail, which agreed well with the experimental data. The intramolecular hydrogen bonding interactions resulted in the shift of vibrational frequencies of hydroxyl to the low band by 12-22 cm(-1) and 24-26 cm(-1) for IM and IT conformations, respectively. Their thermodynamic properties were also calculated based on the harmonic vibrational analysis, including standard heat capacity (C( degrees )p,m), entropy (S( degrees )m), and enthalpy (H( degrees )m). The molecular stability, hydrogen bonding interaction and other electronic properties have been further analyzed by the natural bond orbital (NBO), atoms in molecules (AIM), molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis. PMID- 26994019 TI - How strong is the edge effect in the adsorption of anticancer drugs on a graphene cluster? AB - The adsorption of nucleobase-analog anticancer drugs (fluorouracil, thioguanine, and mercaptopurine) on a graphene flake (C54H18) was investigated by shifting the site at which adsorption occurs from one end of the sheet to the other end. The counterpoise-corrected M06-2X/cc-pVDZ binding energies revealed that the binding stability decreases in the sequence thioguanine > mercaptopurine > fluorouracil. We found that adsorption near the middle of the sheet is more favorable than adsorption near the edge due to the edge effect. This edge effect is stronger for the adsorption of thioguanine or mercaptopurine than for fluorouracil adsorption. However, the edge effect reduces the binding energy of the drug to the flake by only a small amount, <5 kcal/mol, depending on the adsorption site and the alignment of the drug at this site. PMID- 26994020 TI - Stereochemistry and spectroscopic analysis of bis-Betti base derivatives of 2,3 dihydroxynaphthalene. AB - Density functional theory (DFT) was used to study the stereochemistry, thermodynamic stability, and spectra of recently synthesized bis-Betti base derivatives of 2,3-dihydroxynaphthalene obtained through multicomponent reactions of 2,3-dihydroxynaphthalene with aminoisoxazole and benzaldehyde derivatives. The stereochemistry of the products was investigated by theoretically calculating the infrared (IR) and proton nuclear magnetic resonance ((1)H NMR) spectra of the diastereomers and comparing them to the corresponding experimental data. The thermochemical properties of the reactions, including the enthalpy, internal energy, entropy, and Gibbs free energy, were also calculated. The diastereoselectivity of the reactions was estimated from the equilibrium distribution of diastereomers. According to the results, the synthesis of bis Betti bases is exothermic and accompanied by a decrease in entropy. The energy difference between the diastereomers is quite small, but the Gibbs free energy change for the equilibrium syn <-> anti favors the anti over syn configuration. These results are in good agreement with experimental observations. PMID- 26994021 TI - Attaching an alkali metal atom to an alkaline earth metal oxide (BeO, MgO, or CaO) yields a triatomic metal oxide with reduced ionization potential and redirected polarity. AB - The existence of a series of neutral triatomic metal oxides MON and their corresponding cations MON (+) (M = Be, Mg, Ca; N = Li, Na, K) was postulated and verified theoretically using ab initio methods at the CCSD(T)/6-311+G(3df)//MP2/6 311+G(3df) level of theory. The calculations revealed that the vertical ionization potentials (IPs) of the MON radicals (calculated using the outer valence Green's function technique (OVGF) with the 6-311+G(3df) basis set) were ca. 2-3 eV smaller than the IPs of the corresponding MO and NO systems or that of the isolated M atom. Population analysis of the neutral triatomic MON molecules and their corresponding MO counterparts indicated that the attachment of an alkali metal atom to any oxide MO (BeO, MgO, CaO) reverses its polarity, which manifests itself as the redirection of the dipole moment vector. PMID- 26994022 TI - Density functional study of H2O molecule adsorption on alpha-U(001) surface. AB - Periodic density functional theory (DFT) calculations were performed to investigate the adsorption of H2O on U(001) surface. The metallic nature of uranium atom and different adsorption sites of U(001) surface play key roles in the H2O molecular dissociate reaction. The long-bridge site is the most favorable site of H2O-U(001) adsorption configuration. The triangle-center site of the H atom is the most favorable site of HOH-U(001) adsorption configuration. The interaction between H2O and U surface is more evident on the first layer than that on any other two sub-layers. The dissociation energy of one hydrogen atom from H2O is -1.994 to -2.215 eV on U(001) surface, while the dissociating energy decreases to -3.351 to -3.394 eV with two hydrogen atoms dissociating from H2O. These phenomena also indicate that the Oads can promote the dehydrogenation of H2O. A significant charge transfer from the first layer of the uranium surface to the H and O atoms is also found to occur, making the bonding partly ionic. PMID- 26994023 TI - TOP2A copy number and TOP2A expression in uterine benign smooth muscle tumours and leiomyosarcoma. AB - AIMS: To examine TOP2A copy number, TOP2A expression, and its prognostic value in uterine leiomyosarcoma (LMS) and other benign smooth muscle tumours. METHODS: We analysed 37 patients treated for uterine LMS with immunohistochemistry for protein expression and fluorescence in situ hybridisation (FISH) for copy number. Twelve cases of leiomyoma variants (LMVs), 4 smooth muscle tumours of uncertain malignant potential (STUMP) and 23 leiomyomas (LMs) were also included. RESULTS: Eighteen patients with LMS (48.6%) were International Federation of Gynecology and Obstetrics (FIGO) stage I, six (16.2%) were stage II, four (10.8%) were stage III, and nine (24.3%) were stage IV. Twenty-one (56.8%) patients with LMS showed high expression of TOP2A. Greater TOP2A levels were found in patients with stage >=II disease compared with stage I and also in high mitotic index tumours (>20/10 HPF (high power field)). Eleven (36.7%) cases had abnormal TOP2A copy numbers. There was no link between TOP2A copy number and TOP2A expression. All patients with benign smooth muscle tumours had low TOP2A immunohistochemical expression and one (7.7%) patient had TOP2A amplification. TOP2A expression and TOP2A copy number had no impact on disease outcomes. Only the presence of disease outside of the uterus negatively impacted survival compared with early disease (53.4 vs 15.8 months; p<0.001). CONCLUSIONS: TOP2A is highly expressed in advanced LMS but not in non-malignant diseases. TOP2A expression does not correlate with FISH results and does not predict outcome. TOP2A levels are higher in high-mitotic index tumours and in more advanced stages of disease. PMID- 26994024 TI - Development and Evaluation of Ergonomic Interventions for Bucket Handling on Farms. AB - OBJECTIVE: The aim of this study was to introduce and evaluate two interventions, Ergo Bucket Carrier (EBC) and Easy Lift (EL), for youths (and adults) to handle water/feed buckets on farms. BACKGROUND: The physical activities of both adult and youth farm workers contribute to the development of low-back disorders (LBDs). Many of the activities youths perform on farms are associated with increased LBD risk, particularly, the handling of water and feed buckets. METHOD: Seventeen adult and youth participants (10 males and seven females) participated in this study. To assess the risk of LBDs, the participants were instrumented with a three-dimensional spinal electrogonio-meter while lifting, carrying, and dumping water buckets using the traditional method and the two interventions. RESULTS: For both the adult and youth groups, the results showed that the two interventions significantly decrease the magnitudes of LBD risk in many of the tasks evaluated. Overall, the use of the EBC resulted in a 41% reduction in the level of LBD risk for the carrying task and a reduction of 69% for the dumping task. Using the EL, on the other hand, is especially effective for lifting tasks (55% reduction in LBD risk). Results of the subjective response were consistent with the objective evaluations. CONCLUSION: This study demonstrated the potential for ergonomic interventions in reducing LBD risk during the common farming task of bucket handling. APPLICATION: Potential application of this study includes the introduction of the EBC and EL in family farms to reduce the LBD risk among youth and adult farmers. PMID- 26994025 TI - Adverse Events in Children Receiving General Anaesthesia with Laryngeal Mask Airway Insertion. AB - INTRODUCTION: Perioperative adverse events are more common in children compared to adult population. Reporting an adverse event proves effective in identifying problems and helps in prevention and early management. Our objective was to identify the types, incidence, and the time of occurrence of perioperative adverse event. We also aimed to find out whether the occurrence of the types of adverse events differ in children below and above five years. METHODS: This was a prospective study in 242, ASA Physical Status I and II children aged day one to 14 years, receiving general anesthesia with laryngeal mask airway for various elective surgeries. Adverse events observed in the perioperative period were recorded. RESULTS: Adverse events related to respiratory system (n=26, 55%) were the most common followed by cardiovascular system (n= 14, 30%). Adverse events were observed in 24(10%) children in the operating room and in 20 (8%) children in the post anaesthesia care unit. In the operating room, majority (14 of 27, 52%) of the events occurred immediately after removal of laryngeal mask airway. Respiratory events were more common in children below five years (p=0.007), whereas cardiac events were more common in children above five years (p=0.02). CONCLUSIONS: The commonest adverse event in children is related to respiratory system. Adverse events occur more frequently in the operating room, mostly immediately after removal of laryngeal mask airway. Respiratory events are more frequent in children below five years whereas cardiac events are more frequent in children above five years. PMID- 26994026 TI - Targeted Therapy for Renal Cell Carcinoma. AB - INTRODUCTION: Our study aims to evaluate the use of targeted therapy in metastatic renal cell carcinoma Methods: This is a prospective study done over three years from December 2010 to December, 2013.Out of Forty seven patients of metastatic renal cell carcinoma 8(neo-adjuvant cases) were excluded and 39 were included in this study. All patients received Tyrosine kinase inhibitor, sunitinib therapy (50 mg OD, 4/2 scheme). All 39 patients underwent radical nephrectomy prior to sunitinib therapy. Patients were followed up every cycle for their clinical symptoms following sunitinib therapy and every 3 months with chest X-ray, ultra-sonography and bone scan. CT scan was done if needed. A RECIST criterion was used to evaluate the complete, partial and no tumor response. RESULTS: The median survival was 28.5 months (CI 9.253-47.7) and progression free survival (PFS) was 9.16 months(CI 6.08-12.23).According to RECIST, stable disease was found in 6 patients till date and a complete response in two patients. Clear cell histology was found in 30(76.9%) patients, papillary variety in 6(15.39%) patients, chromophobe type was seen in one patient and rest had mixed sarcomatoid papillary and rhabdoid clear cell variety. Twenty four patients (61.5%) had multiple metastases. Most frequent metastasis was seen in lungs in 14 patients (36%) and bone in 12 patients (31%).Metastases were also seen in draining lymph nodes, adrenals, omentum,skin, liver, and brain. CONCLUSIONS: In our cohort, use of sunitinib showed similar outcome to previously published articles. Our study supports the use of sunitinib in metastatic renal cell carcinoma. PMID- 26994027 TI - Phenotypic Characterization of Multidrug-resistant Escherichia Coli with Special Reference to Extended-spectrum-beta-lactamases and Metallo-beta-lactamases in a Tertiary Care Center. AB - INTRODUCTION: The increasing reports on extended-spectrum-beta-lactamase and metallo-beta-lactamase producing Escherichia coli have addressed a potential threat to global health since it is found to be highly resistance to most of the currently available antibiotics including carbapenems. The present study was aimed to determine the antibiogram of extended-spectrum-beta-lactamase and metallo-beta-lactamase producing MDR E. coli isolates from various clinical samples. METHODS: This was a cross-sectional study conducted over a period of seven months from December 2013 to July 2014 at bacteriology laboratory of Tribhuvan University Teaching Hospital. A total of 250 clinical specimens (urine, pus, sputum, blood, body fluid, bile, tissue and central venous pressure line tip) were processed from inpatients, with multidrug-resistant Escherichia coli infections. Standard microbiological techniques were used for isolation and identification of the isolates. The presence of extended-spectrum-beta-lactamase was detected by phenotypic confirmatory test recommended by Clinical and Laboratory Standards Institute and imipenem (IMP) /EDTA combined disc method was performed to detect metallo-beta-lactamase mediated resistance mechanism. RESULTS: We found high level of beta lactamase mediated resistance mechanism as part of multidrug resistance. Among 250 MDR isolates, 60% isolates were extended spectrum-beta-lactamase producers and 17.2% isolates were metallo-beta-lactamase producers. Co-existence of extended-spectrum-beta-lactamase and metallo-beta lactamase identified in 6.8% isolates. CONCLUSIONS: Beta-lactamase mediated resistance mechanisms are accounting very high in the multidrug resistant isolates of E. coli. Therefore, early detection of beta lactamase mediated resistant strains and their current antibiotic susceptibility pattern is necessary to avoid treatment failure and prevent the spread of MDR. PMID- 26994028 TI - Markers of Autolysis in Acute ST Elevation Myocardial Infarction. AB - INTRODUCTION: The availability of reliable noninvasive markers for infarct related artery (IRA) patency status are very limited, otherwise could allow early identification of patients with patent IRA, for whom repeat thrombolysis or rescue percutaneous coronary intervention (PCI) are not necessary. METHODS: We conducted a single centered retrospective study of STEMI patients undergoing primary PCI to determine how various factors such as demographic characteristics, risk markers of coronary heart disease, clinical and blood parameters present differently in patients with higher coronary flow and patent infarct related artery from patients with total occlusion at the time of initial angiography and how they affect in outcome of the disease. RESULTS: MPV level (11.96 fL vs. 10.92 fL, P < 0.001), Lp (a) level (179.57 nmol/l vs 141.16 nmol/l , p < 0.001), CK-MB (290.2 vs. 190.98, P < 0.001), total cholesterol level (4.11 mmol/L vs. 3.8 mmol/L, p < 0.02) in total occlusion group were higher than in the patent IRA group. Wall motion abnormality was 77.2% for 203 patients with total occlusion group and 54.2% for 83 patients with patent IRA group (P<0.01). Mean hospital stay days were higher in total occlusion group as compared to the patent IRA group P < 0.01. CONCLUSIONS: MVP, Lp (a), TC, and CK-MB levels and myocardial wall motion at the presentation may play the role of markers for IRA patency status that will help in early identification of patients with IRA, for whom repeat thrombolysis or rescue PCI may not be required. PMID- 26994029 TI - Intravenous Iron Sucrose Therapy in Iron Deficiency Anemia in Antenatal and Postnatal Patients. AB - INTRODUCTION: Iron deficiency anemia is the most common nutritional deficiency in pregnancy and more common in developing countries which is aggravated due to increased demand and blood loss during delivery. Though there are different methods for treating iron deficiency anemia. Iron sucrose is being used because of its minimal side effects. This study was undertaken to evaluate the response and effect of intravenous iron sucrose given to patient in antenatal and postnatal period with moderate iron deficiency anemia. METHODS: A hospital based prospective study was conducted 1st Jan 2013-30th Dec 2014 in the department of obstetrics and gynecology Kathmandu Medical College, Teaching Hospital Kathmandu, Nepal. Antenatal and postnatal patients with hemoglobin between 5-9 gm% with diagnosed iron deficiency anemia were included in the study. The aim was to bring her hemoglobin level to 11gm%. RESULTS: All together 37 patients were enrolled out of which two patient were dropped due to allergic reaction and 35 patients were included in study. Iron sucrose therapy is effective in achieving target hemoglobin of 11gm/dl in 80% of patients. It showed that intravenous iron sucrose significantly (P < 0.001) increase hemoglobin level within two weeks of therapy without any major adverse effects. CONCLUSIONS: Iron sucrose therapy is safe, effective and well tolerated for the treatment of iron deficiency anemia. Parental iron therapy was effective in increasing hemoglobin, serum ferritin and other hematological parameters in antenatal and postnatal patients with anemia. The treatment will help to reduce the risk of maternal complication during pregnancy and postpartum and its adverse effect to fetus. PMID- 26994030 TI - Intravenous Iron Sucrose Therapy in Iron Deficiency Anemia in Antenatal and Postnatal Patients. AB - INTRODUCTION: Dermatophytosis is a common superficial fungal infection of the skin, hair and nails caused by Trichophyton, Microsporum and Epidermophyton dermatophytic species. Identification of causative dermatophytic species tend to vary with time and place and antifungal sensitivity is of epidemiological concern as well as significant for the treatment with precision at the current scenario of increasing antifungal resistance. The objectives was to study clinicomycological profile and antifungal sensitivity pattern of commonly used azoles in dermatophytosis. METHODS: The prospective analysis of 145 clinically suspected cases of dermatophytosis was conducted from January 2014 to January 2015 at Department of Dermatology of COMS, Bharatpur, Chitwan, Nepal. Cases were evaluated and data recorded as per proforma. Samples were collected for microscopy and culture from skin, hair and nail. Antifungal sensitivity pattern was evaluated by standard disk diffusion technique. RESULTS: Maximum numbers of cases with dermatophytosis were observed between June to September with male to female ratio of 1.4:1. The youngest patient was 3 years and the oldest was 76 years. Tinea corporis (25.5%) was the dominant clnical type observed. Overall direct microscopy (KOH) positivity and culture positivity was 64.8% and 57.2% respectively. Predominant species of dermatophyte isolated was T. mentagrophyte (23.4%). Out of five antifungals used in our study, fluconazole and ketoconazole were found 100% resistant. CONCLUSIONS: This study highlighted the increasing resistance of the antifungals, which is responsible for the treatment failure in dermatophye infections. PMID- 26994031 TI - Perception of Palliative Care among Medical Students in a Teaching Hospital. AB - INTRODUCTION: Palliative care is an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness. Palliative care must be a part of every medical personnel's practice. But still medical education curriculums have not included palliative care in its syllabus, sufficiently due to which most of the health professional are not aware about this specialty. The purpose of this study is to find out the perception of the medical students in palliative care in a teaching hospital. METHODS: A descriptive study was done among 270 undergraduate medical students studying in Institute of Medicine using a self structured pretested questionnaire. Data was entered in Microsoft Excel and analyzed by using SPSS 21. RESULTS: Of the total 270 undergraduate medical students only 152 has heard the word "palliative care". Only 84 students know, palliative care can be provided early in the life threatening illness. Total 80 students know it doesn't intend to postpone and hasten death. Though only 49 students didn't know PC is not included in our curriculum, 227 are interested to learn about it if given any opportunity. CONCLUSIONS: The perception of palliative care medicine is low in first couple of year of medical study. It is increased in clinically exposed students but is surprisingly more in fourth year than final year undergraduate medical students. However, it should be included in undergraduate medical study. PMID- 26994032 TI - Pattern of Pediatric Admissions in a Tertiary Care Hospital of Central Nepal. AB - INTRODUCTION: An understanding of the epidemiological trend in hospital admissions, including morbidity and mortality patterns and the economic impact, is critical for healthcare planning and appropriate resource allocation. As we find very few literature on the pattern of paediatric admissions outside Kathmandu Valley, it is essential to conduct studies in the various parts of the country to determine the paediatric inpatient burden as well resource allocations. METHODS: A retrospective study was carried out at Department of Pediatrics, College of Medical Sciences-Teaching Hospital, Bharatpur, Chitwan, Nepal over a period of one year. All the admissions were analyzed for age, sex, address, seasonal variation, frequency of diseases according to the organ system involved, duration of hospital stay, and the outcome. RESULTS: Out of the total 814 cases admitted 68.8% of the patients were younger than five years. There was male preponderance with male to female ratio of 1.9:1. Majority (43.6%) admissions were from Chitwan itself. Respiratory, gastrointestinal and neurologic conditions were the main cause for admission. The mean duration of hospital stay was 5.28 days and the mortality was only 0.1%. CONCLUSIONS: In this study under five-year patients contributed to 2/3rd of the hospital admissions. Respiratory, gastrointestinal and neurologic conditions were the main cause for admission with pneumonia, URTI and acute gastroenteritis being the most common diseases. PMID- 26994033 TI - Spinal Tuberculosis with Paraplegia in Pregnancy. AB - Spinal tuberculosis leading to paraplegia is uncommon in pregnancy and is a diagnostic and therapeutic challenge. We report a case of tubercular paraplegia presenting at 35 weeks of gestation. She was managed with Anti-tubercular drugs and did not require surgical intervention. Her neurological status improved and she was allowed to go in labour. She delivered a healthy term infant by cesarean. At three months follow-up, both mother and child are doing well. PMID- 26994034 TI - Complete Bilateral Calcified Psoas Abscess- Rare Sequelae of Untreated Pott's Spine. AB - Although rare in the western world; psoas abscess is a frequent finding in Indian sub continent associated with Pott's spine. Untreated Pott's spine may lead to various sequelae like destruction of vertebra, kyphosis, paraplageia etc which in modern world is amenable to anti-tubercular drugs and surgical management. We report a case of untreated Pott's spine with bilateral calcified psoas abscess with kyphosis. To the best of our knowledge no such case of complete bilateral calcified psoas abscesses has been reported earlier. We want to discuss this case with relevant literature review and its influence on treatment plan. PMID- 26994035 TI - Delayed Presentation of Catheter-related Subclavian Artery Pseudoaneurysm. AB - Central venous catheterization is a common diagnostic and therapeutic procedure in modern clinical practice. Pseudoaneurysms of the subclavian artery are rare and usually occur immediately after the causative event, whether the cause was trauma or a medical procedure. Here, we report a case of a 71-year-old woman with delayed presentation of catheter-related subclavian pseudoaneurysm. The patient's symptoms began two weeks after the initial catheterization, probably because of slow leakage of blood from the injured subclavian artery caused by incomplete compression of the puncture site and uremic coagulopathy. She was successfully treated with ultrasound-guided thrombin and angiography-guided histoacryl injection without stent insertion or surgery. PMID- 26994036 TI - A Case of Successful Management of Guillain-Barre Syndrome in Pregnancy. AB - Guillain-Barre' syndrome complicating pregnancy is a rare event which carries a high maternal risk. We presented a case of 23 years old pregnant lady diagnosed with GBS in third trimester who deteriorated after termination of delivery of the new born. Despite the availability of intravenous immunoglobulin and plasmapheresis and complications like ventilator associated pneumonia, tracheostomy, autonomic instability, patient was successfully managed due to a meticulous multidisciplinary involvement in our intensive care unit. PMID- 26994037 TI - Rhabdomyolysis Due to Severe Hypophosphatemia in Diabetic Ketoacidosis. AB - Rhabdomyolysis is a syndrome characterized by injury to skeletal muscle fibers with disruption and release of toxic metabolites into circulation. It is characterized by triad of muscle weakness, myalgia and dark urine and is associated with increased creatine kinase and lactate dehydrogenase. A severely malnourished 10 year old girl with severe diabetic ketoacidosis as hemr initial presentation of type 1 diabetes mellitus developed rhabdomyolysis (CK- 12,000 U/L) with non-oliguric renal failure during her initial course of hospital stay. The possible cause of her RM was attributed to severe hypophosphatemia (minimum serum phosphate, 0.8 mg/dL). Management of diabetic ketoacidosis phosphate supplementation and urinary alkalinization with diuresis improved her clinical course. She was discharged on Day 9 with Insulin. We recommend frequent monitoring of serum phosphate during early period of DKA, particularly in malnourished children, and its normalization in case of severe hypophosphatemia. PMID- 26994038 TI - The Feeding Tube- a Simple Yet Handy Aid to Intubate an Unanticipated Difficult Pediatric Airway. AB - Pediatric intubation requires certain unique set of additional skills compared to intubating adults. The challenges of successfully intubation of a child increases as the age and size of the child decrease and are compounded when airway difficulties arise for various reasons. Often in the rural setting, such procedures may have to be carried out by health care personnel who get trained on the-job, and in the absence of adequate technological back-up. This leads to an increased incidence of failed intubations which can have devastating complications, especially in the pediatric age group. We describe a simple technique which helped us while intubate a 40-day old infant, without any major catastrophes. PMID- 26994039 TI - Anaesthetic Management of Patients with Takayasu's Arteritis for Open Cholecystectomy. AB - Takayasu's arteritis is a well known yet rare form of large vessel vasculitis.1 This inflammatory disease often affects the ascending aorta and aortic arch, causing obstruction of the aorta and its major arteries.2 Anaesthetic management for these patients is complicated by severe hypertension, end-organ dysfunction, stenosis of major blood vessles and difficulties in monitoring blood pressure.1 We present two patients who underwent open cholecystectomy under neuraxial anaesthesia. We have discussed about various perioperative issues and their management. PMID- 26994040 TI - Face-to-face Training as an Effective Approach for Teaching Rotahaler Technique in Newly Diagnosed Patients of Asthma and COPD. AB - INTRODUCTION: This study aimed to evaluate the effectiveness of face-to-face training for teaching rotahaler technique in newly diagnosed patients of asthma and chronic obstructive pulmonary disease (COPD). METHODS: A hospital-based study was conducted among twenty patients who were prescribed rotahaler for the first time. Patients received face-to-face training on rotahaler technique from pharmacist using GINA guidelines. The patients rotahaler technique was assessed after two weeks of training and scored one for correct and zero for incorrect steps. Descriptive statistics were performed. RESULTS: The mean age of the study population was 48.85+/-20.49 years. Eleven (55%) patients were females. Thirteen (65%) patient were not formally educated in school. Fourteen patients (70%) were able to perform all the steps correctly giving overall median score of eight (7 8). CONCLUSIONS: Face-to-face training seems to be effective approach for teaching rotahaler technique in asthma and COPD patients. PMID- 26994041 TI - In vivo evidence for long-term vascular remodeling resulting from chronic cerebral hypoperfusion in mice. AB - We have characterized both acute and long-term vascular and metabolic effects of unilateral common carotid artery occlusion in mice by in vivo magnetic resonance imaging and positron emission tomography. This common carotid artery occlusion model induces chronic cerebral hypoperfusion and is therefore relevant to both preclinical stroke studies, where it serves as a control condition for a commonly used mouse model of ischemic stroke, and neurodegeneration, as chronic hypoperfusion is causative to cognitive decline. By using perfusion magnetic resonance imaging, we demonstrate that under isoflurane anesthesia, cerebral perfusion levels recover gradually over one month. This recovery is paralleled by an increase in lumen diameter and altered tortuosity of the contralateral internal carotid artery at one year post-ligation as derived from magnetic resonance angiography data. Under urethane/alpha-chloralose anesthesia, no acute perfusion differences are observed, but the vascular response capacity to hypercapnia is found to be compromised. These hemispheric perfusion alterations are confirmed by water [15O]-H2O positron emission tomography. Glucose metabolism ([18F]-FDG positron emission tomography) or white matter organization (diffusion weighted magnetic resonance imaging) did not show any significant alterations. In conclusion, permanent unilateral common carotid artery occlusion results in acute and long-term vascular remodeling, which may have immediate consequences for animal models of stroke but also vascular dementia. PMID- 26994042 TI - A role of the sodium pump in spreading ischemia in rats. AB - In rats, spreading depolarization induces vasodilation/hyperemia in naive tissue but the inverse response when artificial cerebrospinal fluid is topically applied to the brain containing (a) a nitric oxide-lowering agent and (b) elevated K+. The inverse response is characterized by severe vasoconstriction/ischemia. The perfusion deficit runs together with the depolarization in the tissue (=spreading ischemia). Here, we found in male Wistar rats that pre-treatment with artificial cerebrospinal fluid containing elevated K+ in vivo led to a selective decline in alpha2/alpha3 Na+/K+-ATPase activity, determined spectrophotometrically ex vivo. Moreover, spreading ischemia, recorded with laser-Doppler flowmetry and electrocorticography, resulted from artificial cerebrospinal fluid containing a nitric oxide-lowering agent in combination with the Na+/K+-ATPase inhibitor ouabain at a concentration selectively inhibiting alpha2/alpha3 activity. Decline in alpha2/alpha3 activity results in increased Ca2+ uptake by internal stores of astrocytes, vascular myocytes, and pericytes since Ca2+ outflux via plasmalemmal Na+/Ca2+-exchanger declines. Augmented Ca2+ mobilization from internal stores during spreading depolarization might enhance vasoconstriction, thus, contributing to spreading ischemia. Accordingly, spreading ischemia was significantly shortened when intracellular Ca2+ stores were emptied by pre treatment with thapsigargin, an inhibitor of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). These findings might have relevance for clinical conditions, in which spreading ischemia occurs such as delayed cerebral ischemia after subarachnoid hemorrhage. PMID- 26994043 TI - Cerebral haemodynamics during experimental intracranial hypertension. AB - Intracranial hypertension is a common final pathway in many acute neurological conditions. However, the cerebral haemodynamic response to acute intracranial hypertension is poorly understood. We assessed cerebral haemodynamics (arterial blood pressure, intracranial pressure, laser Doppler flowmetry, basilar artery Doppler flow velocity, and vascular wall tension) in 27 basilar artery-dependent rabbits during experimental (artificial CSF infusion) intracranial hypertension. From baseline (~9 mmHg; SE 1.5) to moderate intracranial pressure (~41 mmHg; SE 2.2), mean flow velocity remained unchanged (47 to 45 cm/s; p = 0.38), arterial blood pressure increased (88.8 to 94.2 mmHg; p < 0.01), whereas laser Doppler flowmetry and wall tension decreased (laser Doppler flowmetry 100 to 39.1% p < 0.001; wall tension 19.3 to 9.8 mmHg, p < 0.001). From moderate to high intracranial pressure (~75 mmHg; SE 3.7), both mean flow velocity and laser Doppler flowmetry decreased (45 to 31.3 cm/s p < 0.001, laser Doppler flowmetry 39.1 to 13.3%, p < 0.001), arterial blood pressure increased still further (94.2 to 114.5 mmHg; p < 0.001), while wall tension was unchanged (9.7 to 9.6 mmHg; p = 0.35).This animal model of acute intracranial hypertension demonstrated two intracranial pressure-dependent cerebroprotective mechanisms: with moderate increases in intracranial pressure, wall tension decreased, and arterial blood pressure increased, while with severe increases in intracranial pressure, an arterial blood pressure increase predominated. Clinical monitoring of such phenomena could help individualise the management of neurocritical patients. PMID- 26994044 TI - Neuronal pannexin-1 channels are not molecular routes of water influx during spreading depolarization-induced dendritic beading. AB - Spreading depolarization-induced focal dendritic swelling (beading) is an early hallmark of neuronal cytotoxic edema. Pyramidal neurons lack membrane-bound aquaporins posing a question of how water enters neurons during spreading depolarization. Recently, we have identified chloride-coupled transport mechanisms that can, at least in part, participate in dendritic beading. Yet transporter-mediated ion and water fluxes could be paralleled by water entry through additional pathways such as large-pore pannexin-1 channels opened by spreading depolarization. Using real-time in vivo two-photon imaging in mice with pharmacological inhibition or conditional genetic deletion of pannexin-1, we showed that pannexin-1 channels are not required for spreading depolarization induced focal dendritic swelling. PMID- 26994045 TI - Acquired torticollis due to primary pyomyositis of the paraspinal muscles in an 11-year-old boy. AB - Torticollis is characterised by tilting and rotation of the cervical spine in opposite directions. Causes can be congenital or acquired. Primary pyomyositis is a rare subacute deep bacterial infection of skeletal muscles that typically affects individuals under 20 years of age from tropical countries. Infrequently, pyomyositis occurs in individuals from temperate regions, usually in immunocompromised adults, and this is defined as secondary pyomyositis. We report a case of acquired torticollis due to primary pyomyositis of the paraspinal muscles in a previously healthy boy from the UK. A prolonged course of antibiotics and physiotherapy led to a complete resolution of his illness. We review how to differentiate pyomyositis from focal myositis, a more common inflammatory muscular cause of acquired torticollis. PMID- 26994046 TI - First bite syndrome: a complication of carotid endarterectomy. AB - First bite syndrome (FBS) is an uncommon pain syndrome characterised by severe cramping or spasm in the parotid region with the first bite of each meal. The proposed pathogenesis is sympathetic denervation of the parotid gland secondary to iatrogenic injury with resultant cross-stimulatory parasympathetic hypersensitivity response. FBS is a potential sequela of surgeries involving the infratemporal fossa, parapharyngeal space and/or deep lobe of the parotid gland, however, only four cases of FBS secondary to carotid endarterectomy have been documented to date. We present a case and management of a 77-year-old man who developed FBS after an ipsilateral carotid endarterectomy, to raise awareness of this complication among surgeons who operate in the neck region. PMID- 26994047 TI - Haemodynamic instability of uncommon aetiology in Switzerland. AB - In Switzerland, vitamin C deficiency is a rare condition. Nonetheless, in clinical practice, there are some patients exhibiting a vitamin C deficiency as a result of an unbalanced diet or intestinal malabsorption. We report the clinical history of a 55-year-old man known for alcoholism and insufficient intake of fresh fruits and vegetables. He was admitted to the intensive care unit, for haemodynamic instability caused by blood loss due to fragile vessels (skin, gastrointestinal). Further analyses revealed a severe lack of vitamin C. The patient received a high dose of intravenous substitutive treatment, leading to a favourable clinical outcome. PMID- 26994048 TI - Lithium toxicity after Roux-en-Y bariatric surgery. AB - A 61-year-old woman with medical history significant for morbid obesity, type II diabetes mellitus, nephrogenic diabetes insipidus and bipolar disorder, had been stable on lithium carbonate therapy for several years. She had undergone a Roux en-Y bypass surgery and, at the time of her surgery, her lithium level was found to be 0.61 mEq/L on a maintenance dose of 600 mg orally twice per day. She was discharged 8 days postoperatively on the same lithium dose, but presented to the emergency department 12 days postoperatively with signs of lithium toxicity. Her lithium level was elevated to 1.51 mEq/L and she was treated for lithium toxicity with supportive care and, ultimately, reduction of her lithium dose. Clinicians should be aware that dramatic and poorly understood changes in drug absorption may occur after bariatric surgery. PMID- 26994049 TI - Spontaneous rupture of an intrahepatic aneurysm of the right hepatic artery caused by segmental arterial mediolysis. AB - Segmental arterial mediolysis (SAM) is a non-arteriosclerotic, non-inflammatory arteriopathy characterised by dissecting aneurysms and most commonly found in abdominal arteries. A rupture of a visceral artery aneurysm is generally associated with high mortality. We present the case of a 57-year-old woman with a rupture of an intrahepatic aneurysm that led to intra-abdominal haemorrhage. The patient was surgically treated by evacuating the abdominal haematoma and ligature of the right hepatic artery. Histology of the right hepatic artery revealed the diagnosis of SAM. Six months postoperatively, the patient was in excellent physical condition with normal liver function and arterial blood flow of the right hepatic sections over collateral circulation. PMID- 26994050 TI - Dawn of a new era: the completely interventionally treated patient. AB - A frail 75-year-old woman with permanent atrial fibrillation and angina pectoris was admitted to our department for further evaluation. Echocardiography revealed concurrent severe aortic valve stenosis. Furthermore, significant coronary artery stenoses were identified on the coronary angiogram. We chose the following treatment strategy: first, two drug eluting stents were implanted successfully in the left anterior descending and circumflex artery, respectively. Second, a 23 mm Core Valve bioprosthesis (Medtronic Inc, Minneapolis, Minnesota, USA) was implanted without complications within the same session. Two weeks after hospital discharge, the patient showed up at our outpatient department, with a symptomatic complete atrioventricular-block with an escape rhythm of 35 bpm. Thus, finally, a leadless pacemaker Micra (Medtronic Inc) was implanted via a transvenous transfemoral access without any complications. PMID- 26994051 TI - Anterior spinal fixation for recollapse of cemented vertebrae after percutaneous vertebroplasty. AB - Although recollapse after percutaneous vertebroplasty (PV) is a serious complication that needs salvage surgery, there is no consensus regarding the best operative treatment for this failure. We present cases of 3 patients, diagnosed as having thoracic osteoporotic vertebral fractures, who had undergone PV at other institutes. Within less than half a year, recollapse occurred at the cemented vertebrae in all 3 patients, and we conducted anterior spinal fixation (ASF) on them. In all cases, ASF relieved the patient's severe low back pain, and there was no recurrence of symptoms during the follow-up period of 6 years, on average. ASF is the optimal salvage procedure, since it allows for the direct decompression of nerve tissue with reconstruction of the collapsed spinal column, and preservation of the ligaments and muscles that stabilise the posterior spine. Surgeons who perform PV need to be able to assess this failure early and to perform spinal fixation. PMID- 26994052 TI - A case of psoriasis pustolosa palmaris induced by cetuximab. AB - Cetuximab is a monoclonal antibody that competitively inhibits the epidermal growth factor receptor (EGFR). It is used for the treatment of metastatic colorectal cancer after first-line therapy. We report the first case of a pustular psoriasiform drug eruption induced by cetuximab in a patient with colorectal cancer. This paradoxical side effect could be the result of an imbalance in downstream molecular pathways due to the EGFR signal blockade that could, in selected patients, induce alternative signalling pathways related to keratinocyte proliferation. PMID- 26994053 TI - A malignant cause of hypoglycaemia: a metastatic insulin-secreting pancreatic neuroendocrine carcinoma. AB - Most cases of insulinomas are benign. We report a case of a malignant form of insulinoma. A 46-year-old man presented with behavioural changes associated with hypoglycaemia. Diagnostic work up revealed high serum insulin, high C-peptide and low glucose levels, compatible with endogenous hyperinsulinaemic hypoglycaemia. CT imaging of the abdomen revealed a pancreatic head mass and multiple liver masses. Biopsy of the pancreatic mass revealed a grade three pancreatic neuroendocrine carcinoma. Histological analysis of a liver mass showed that it was identical to the pancreatic mass, confirming its metastatic nature. The patient underwent distal pancreatectomy with en bloc splenectomy. There was persistence of hypoglycaemic symptoms after removal of the pancreatic mass, suggesting that the liver metastases were also functioning. Symptoms were controlled by diazoxide and octreotide long-acting release. The patient is already 1 year postsurgery with no recurrence of severe hypoglycaemia, and he has good functional capacity and has returned to his office job. PMID- 26994054 TI - Intraocular metallic foreign body causing branch retinal vein occlusion. AB - We report a case of a 40-year-old man with post-traumatic cataract and an intraocular metallic foreign body (IOFB) lying on the retinal surface causing a superotemporal branch retinal vein occlusion. The case was managed using lens aspiration with pars plana vitrectomy and IOFB removal. We only found two previous reports of such a foreign body causing a vascular occlusion. The possibility of a vascular occlusion occurring due to a foreign body within or close to the optic disc is highlighted. PMID- 26994055 TI - Diffuse large B-cell lymphoma of the adrenal gland: a rare cause of primary adrenal insufficiency. AB - Although it is a rare entity, primary lymphoma of the adrenal gland should be considered in the differential diagnosis of bilateral nodular adrenal lesions, particularly when there is evidence of associated adrenal insufficiency. We describe the case of an 83-year-old woman admitted to the emergency department due to a month's history of asthenia, weight loss, anorexia and nausea. Abdominopelvic CT showed bilateral nodular lesions of adrenal glands and a stimulation test with tetracosactide was compatible with primary adrenal insufficiency. CT-guided biopsy of the left adrenal gland was performed, and histopathological results were consistent with diffuse large B-cell lymphoma. Positron emission tomography (18)F-fluorodeoxyglucose detected two intensely hypermetabolic lesions limited to both adrenal glands. Replacement therapy with hydrocortisone 15 mg/day and fludrocortisone 0.1 mg/day was promptly started and chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone was initiated after haematology-oncology consultation. PMID- 26994056 TI - Left circumflex artery supplying the territory of right coronary artery: an extremely rare variant of a congenital single coronary artery. PMID- 26994057 TI - Pleural effusion of malignant aetiology: cell block technique to establish the diagnosis. AB - We describe cases of two previously healthy women presenting with progressively worsening breathlessness for 1-2 months. In both cases, physical examination was suggestive of a left-sided pleural effusion, confirmed by chest X-ray. Analysis of aspirated fluid showed a lymphocytic exudate, but cytological analysis was negative for malignancy in both patients. CT scan revealed malignancies as the underlying cause of the effusions. Both patients were managed with intercostal drainage in order to collect a sufficient amount of pleural fluid to perform a new technique in our hospital: cell block. This proved to be extremely useful in assessing the definitive diagnosis and management of both women. We briefly discuss the approach to a malignant pleural effusion and the aid of this not-so new technique. PMID- 26994058 TI - Initial Validation of the Sleep Disturbances in Pediatric Cancer Model. AB - OBJECTIVE : The current study evaluates content validity of the Sleep Disturbance in Pediatric Cancer (SDPC) model using qualitative and quantitative stakeholder input. METHODS : Parents of children (aged: 3-12 years) with acute lymphoblastic leukemia (n = 20) and medical providers (n = 6) participated in semi-structured interviews about child sleep during cancer treatment. They also rated SDPC model component importance on a 0-4 scale and selected the most relevant sleep-related intervention targets. RESULTS : Qualitatively, parents and providers endorsed that changes in the child's psychosocial, environmental, and biological processes affect sleep. Stakeholders rated most model components (parent: 32 of 40; provider: 39 of 41) as important (>2) to child sleep. Parents were most interested in interventions targeting difficulty falling asleep and providers selected irregular sleep habits/scheduling, though groups did not differ significantly. CONCLUSIONS : Stakeholders supported SDPC content validity. The model will inform subsequent measure and intervention development focusing on biological and behavioral factors most salient to sleep disturbances in pediatric cancer. PMID- 26994059 TI - An Evaluation of the Children's Report of Sleep Patterns Using Confirmatory and Exploratory Factor Analytic Approaches. AB - OBJECTIVE: To explore the psychometric properties of the Children's Report of Sleep Patterns (CRSP) in school-aged children by conducting a factor analysis of the Sleepiness Scale and the Sleep Disturbances Scales. METHODS: Participants included 155 children from two elementary schools (Mage = 9.82) who completed the self-report CRSP. A confirmatory factor analysis (CFA) was conducted using the originally hypothesized structure. A subsequent exploratory factor analysis (EFA) was conducted to determine an alternative factor structure. RESULTS: CFA revealed that the hypothesized factor structure was not supported. The EFA produced an alternative six-factor solution, which supports the conceptualization of three new scales, Restless Legs Report, Sleep Initiation, and Sleep Maintenance/Night Wakings. CONCLUSION: The revised measure adds increased specificity with scales related to insomnia and restless leg symptoms. Researchers and clinicians interested in using the CRSP should continue to assess its validity by exploring the relationship between the measure and objective measures of sleep behavior. PMID- 26994060 TI - The Impact of Posttraumatic Stress Disorder on the 6-Month Outcomes in Collaborative Care Management for Depression. AB - Posttraumatic stress disorder (PTSD) has symptoms that exist along a spectrum that includes depression and the 2 disorders may coexist. Collaborative care management (CCM) has been successfully used in outpatient mental health management (especially depression and anxiety) with favorable outcomes. Despite this, there exist limited data on clinical impact of a diagnosis of PTSD on depression outcomes in CCM. The present study used a retrospective cohort design to examine the association of PTSD with depression outcomes among 2121 adult patients involved in CCM in a primary care setting. Using standardized self report measures, baseline depression scores and 6-month outcome scores were evaluated. Seventy-six patients had a diagnosis of PTSD documented in their electronic medical record. Patients with PTSD reported more severe depressive symptoms at baseline (Patient Health Questionnaire-9 score of 17.9 vs 15.4, P < .001) than those without PTSD. Controlling for sociodemographic and clinical characteristics, a clinical diagnosis of PTSD was associated with lower odds (AOR = 0.457, CI = 0.274-0.760, P = .003) of remission at 6 months and was also associated with higher odds (AOR = 3.112, CI = 1.921-5.041, P < .001) of persistent depressive symptoms at 6 months after CCM. When coexisting with depression, a diagnosis of PTSD was associated with worse depression outcomes, when managed with CCM in primary care. Opportunities still exist for more aggressive management of depression in these patients to help improve remission as well as reduce persistent depressive symptoms. PMID- 26994061 TI - Vitamin D and Lung Function Decline in Adults With Asthma: The HUNT Study. AB - We investigated whether low 25-hydroxyvitamin D (25(OH)D) levels were associated with more lung function decline in adults with asthma and whether this association was modified by smoking status or inhaled corticosteroid (ICS) use. We analyzed data on 395 adults with asthma from the Nord-Trondelag Health Study (1995-2008), Norway. Plasma 25(OH)D and lung function were measured at baseline, and lung function measurements were repeated at follow-up, approximately 11 years later. Linear regression was used to estimate lung function decline. Participants with low 25(OH)D (<50 nmol/L) had more decline in lung function measurements for forced expiratory volume in 1 second (FEV1) (388 mL), forced vital capacity (298 mL), and the FEV1/forced vital capacity ratio (3.7%) over the follow-up, compared with those with high 25(OH)D (>=50 nmol/L) who declined 314 mL, 246 mL, and 3.0%, respectively (P = 0.08, 0.30, and 0.23, respectively). The associations were stronger in never smokers and non-ICS users. In never smokers, low 25(OH)D levels were associated with more decline in FEV1 (445 vs. 222 mL) (P = 0.01). In non-ICS users, low 25(OH)D levels were associated with more decline in FEV1 (467 vs. 320 mL) (P = 0.02). Low serum 25(OH)D levels were weakly associated with more lung function decline in adults with asthma, and stronger associations were observed in never smokers and non-ICS users. PMID- 26994062 TI - The Epidemiology of Herpes Zoster After Varicella Immunization Under Different Biological Hypotheses: Perspectives From Mathematical Modeling. AB - The impact of varicella vaccination on the epidemiology of herpes zoster (HZ) critically depends on the mechanism of immunological boosting, through which reexposures to varicella-zoster virus are thought to reduce the individual risk of HZ development. However, the qualitative and quantitative dynamics of this process are largely unknown. Consequently, mathematical models evaluating immunization strategies need to rely on theoretical assumptions. Available varicella-zoster virus models can be classified in 3 main families according to the postulated effect of exogenous boosting: 1) progressive accumulation of immunity following repeated reexposures; 2) partial protection that wanes over time; or 3) full but temporary immunity against HZ. In this work, we review and compare quantitative predictions from the 3 modeling approaches regarding the effect of varicella immunization on HZ. All models predict a qualitatively similar, but quantitatively heterogeneous, transient increase of HZ incidence. In particular, novel estimates from the progressive immunity model predict the largest increase in natural HZ and the largest incidence of HZ cases from reactivation of the vaccine strain, which in the long term will likely outnumber prevaccination numbers. Our results reinforce the idea that a better understanding of HZ pathogenesis is required before further mass varicella immunization programs are set out. PMID- 26994063 TI - Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. AB - Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls. PMID- 26994064 TI - Age at Menarche and Gallstone Disease in Middle-Aged Women. AB - The goal of this study was to explore the association between age at menarche and gallstone disease (GSD) in Korean women and to determine whether any of the observed associations were mediated by adult adiposity. A cross-sectional study was performed on 83 275 Korean women, aged 30 years or older, who underwent a health checkup examination between March 2011 and April 2013. Information regarding age at menarche was collected using standardized, self-administered questionnaires. Gallstone disease was defined as either having gallstones or having had a cholecystectomy based on ultrasound. Logistic regression models were used to evaluate the association between age at menarche and GSD. Of the 83 275 women evaluated in this study, 3341 had GSD. Age at menarche was negatively associated with the prevalence of GSD. In a multivariable-adjusted model adjusting for potential confounders including reproductive factors and body weight at age 20, the odds ratios (95% confidence intervals) for GSD comparing menarche at <12, 12, 14, 15, and 16 to 18 years to menarche at 13 years were 1.46 (1.23-1.75), 1.19 (1.04-1.35), 0.97 (0.87-1.09), 0.92 (0.82-1.03), and 0.89 (0.78 1.02), respectively (P for trend <.001). Adjusting for adult body mass index or percentage fat mass (%) partially reduced these associations; however, they remained statistically significant. Early menarche was associated with increasing prevalence of GSD in a large sample of middle-aged women. The findings of this study extend the range of adverse health outcomes associated with early menarche and suggest that obesity prevention strategies could be useful for reducing the risk of GSD in women who experience early menarche. PMID- 26994065 TI - Inhibition of Wnt Inhibitory Factor 1 Under Hypoxic Condition in Human Umbilical Vein Endothelial Cells Promoted Angiogenesis in Vitro. AB - Placentation is a complicated process critical for maternal-fetal exchange of nutrients and gases that includes stepwise vasculogenesis and angiogenesis. Wnt inhibitory factor 1 (WIF1) is a secreted Wnt antagonist that acts as a tumor suppressor gene by antagonizing angiogenesis and proliferation and inducing apoptosis. The purpose of this study was to investigate the function of WIF1 on placental angiogenesis in human umbilical vein endothelial cells (HUVECs) under hypoxic conditions. We found that WIF1 was diversely expressed in placental vascular endothelial cells at different points during gestation and was weaker in the early placenta than in the term placenta. We validated the antiangiogenesis role of WIF1 by inhibiting proliferation, tube formation and migration, and inducing apoptosis of endothelial cells through antagonizing Wnt/beta-catenin signaling pathway. We also identified that hypoxic conditions similar to the early placenta inhibited the expression of WIF1 and reversed the antiangiogenesis of WIF1 in HUVECs. In conclusion, our present study supported the hypothesis that WIF1 is crucial as a negative regulator of the functions of endothelial cells in angiogenesis and that hypoxia plays an important role in controlling WIF1 expression and angiogenesis. We also demonstrated that Wnt/beta-catenin signaling pathway was activated in correspondence with the suppression of WIF1 in the angiogenesis of endothelial cells under hypoxic conditions. PMID- 26994066 TI - Laparoscopic Surgery: A New Technique to Induce Endometriosis in a Mouse Model. AB - BACKGROUND: This prospective pilot study was designed to induce endometriosis in a mouse model using laparoscopy, a less invasive and more precise approach than laparotomy. We aimed to achieve a peritoneal implant rate of at least 50% by varying both duration of anesthesia and intra-abdominal insufflation pressure. METHODS: Female BALB/cANnCrl mice in metestrus or diestrus were used as donors (n = 5) or recipients (n = 20) of uterine transplant tissue. Each recipient mouse was laparoscopically inoculated with 10 uterine pieces (range: 10-12) from donor mice into the abdominal cavity. Before starting the study, recipient mice were randomly assigned to 4 groups with variable duration of anesthesia (ketamine/xylazine or pentobarbital) and variable intra-abdominal pressure (5 or 15 mm Hg). One week after laparoscopy, endometriosis incidence and peritoneal implant take rate were documented visually during laparotomy. The retrieved lesions were histologically analyzed. RESULTS: Laparoscopic inoculation of uterine pieces in recipient mice resulted in an endometriosis incidence of 100% (20/20 animals) and an individual peritoneal implant take rate of 60% (121/206), ranging from 17% (2/12) till 83% (10/12), without differences between the 4 subgroups, and with a histological confirmation rate of 92% (58/63). CONCLUSIONS: To the best our knowledge, this is the first report showing that endometriosis can be induced by laparoscopic surgery in rodents, with a 100% incidence and a median peritoneal implant take rate of 60%. This laparoscopic model offers important advantages over traditional laparotomy models that are limited by surgery-associated trauma and/or adhesion formation. PMID- 26994067 TI - Correlation Between the Clinical Parameters and Tissue Phenotype in Patients Affected by Deep-Infiltrating Endometriosis. AB - The current study aimed to identify and validate an applicable immunohistochemistry panel including Ki-67, c-MYC, estrogen receptor-alpha (ER alpha), and progesterone receptor isoforms A/B (PR-A/B) in correlation with clinicopathological parameters in patients affected by deep infiltrating endometriosis. Tissue microarrays were prepared from a cohort of 113 patients. Phenotypic profile of the panel molecules was evaluated in glands and stroma in parallel with microvessels and stroma density measurements. Principal component analysis was performed on 8 immunohistochemical variables, 2 histological variables, and 8 subgroups of clinical parameters. The immunohistochemical profiling showed consistent Ki-67 immunostaining in 17.9% of the samples and c MYC in 83.1%, while intense ER-alpha immunoreactivity was detected in 84% of the samples and PR-A/B isoforms in 24.1% of them. The combination of clinical parameters and tissue phenotype allowed a stratification of endometriosis affected patients. Such novel phenotypical and clinical correlation could be helpful in the future studies for a better stratification of the disease aiming at a personalized patient care. PMID- 26994068 TI - Inequality in disability-free life expectancies among older men and women in six countries with developing economies. AB - BACKGROUND: It is unclear whether the increase in life expectancy (LE) globally is coupled with a postponement of morbidity and disability. Evidence on trends and determinants of disability-free life expectancies (DFLEs) are available in high-income countries but less in low and middle-income countries (LMICs). This study examines the levels of and inequalities in LE, disability and DFLE between men and women across different age groups aged 50 years and over in six countries with developing economies. METHODS: This study utilised the cross-sectional data (n=32 724) from the WHO Study on global AGEing and adult health (SAGE) in China, Ghana, India, Mexico, the Russian Federation and South Africa in 2007-2010. Disability was measured with the activity of daily living (ADL) instrument. The DFLE was estimated using the Sullivan method based on the standard period life table and ADL-disability proportions. RESULTS: The disability prevalence ranged from 13% in China to 54% in India. The prevalence of disability was highest and occurred at younger age in both sexes in India. Women were more disadvantaged with higher prevalence of disability across all age groups, and the situation was worst among older women in Mexico and the Russian Federation. Though women had higher LE, their proportion of remaining LE free from disability was lower than men. CONCLUSIONS: There are inequalities in the levels of disability and DFLE among men and women in different age groups among people aged over 50 years in these six countries. Countermeasures to decrease intercountry and gender gaps in DFLE, including improvements in health promotion and healthcare distribution, with a gender equity focus, are needed. PMID- 26994069 TI - Monophosphoryl lipid A-induced pro-inflammatory cytokine expression does not require CD14 in primary human dendritic cells. AB - OBJECTIVE: To elucidate if TLR4-mediated MyD88 and TRIF signalling by the clinically applicable Lipopolysaccharide (LPS)-derivative monophosphoryl lipid A (MPLA) in primary human dendritic cells requires LPS cofactors LPS-binding protein (LBP) and CD14. METHODS: Cytokine production by monocyte-derived DCs stimulated with MPLA or LPS was determined using ELISA. To investigate involvement of CD14 for action of LPS or MPLA, CD14 was inhibited using blocking antibodies or down-modulated using specific siRNA. To assess involvement of LBP monocyte-derived DCs were stimulated in serum-free culture medium in absence or presence of purified LBP. RESULTS: LBP and CD14 are not required for and do not enhance the capacity of MPLA to induce MyD88- and TRIF-dependent pro-inflammatory IL-6 and TNF-alpha. Interestingly, although CD14 is required for TRIF-dependent downstream events in mice, we show that in human CD14 is redundant for MPLA induced TRIF-dependent chemokine production. CONCLUSIONS: These findings provide novel insight in the modes of action of MPLA in human and show that, compared to LPS, MyD88 and TRIF signalling in dendritic cells by MPLA is not mediated nor amplified by TLR4 cofactors. This gives insight why MPLA induces immune activation without provoking toxicity in human and clarifies why MPLA can be used as activating compound for clinically applicable immuno-activatory cellular products grown in serum-free regimens. PMID- 26994070 TI - Attachment in eating-disordered outpatients with and without borderline personality disorder. AB - This study aims at examining the attachment states of mind in 50 female outpatients with eating disorders compared with 50 matched control participants using the Adult Attachment Interview. Moreover, the differences in attachment states of mind among eating-disordered women with and without borderline personality disorders' diagnosis were explored. The results showed an over representation of insecure-dismissing and unresolved states of mind in clinical group compared to controls. Patients with both diagnosis showed higher scores on involving anger and unresolved loss compared with those with only eating disorder. Implications for further research and clinical practice are discussed. PMID- 26994071 TI - Sensory Processing Difficulties in Opsoclonus-Myoclonus Syndrome: A Pilot Project of Presentation and Possible Prevalence. AB - Opsoclonus-myoclonus syndrome is a rare but serious neurological condition resulting in loss of control of eye movements, often accompanied by difficulties in posture and movement control with reports of sensory sensitivities potentially impacting on behavior. This pilot study characterizes the presence of atypical sensory behaviors in opsoclonus-myoclonus syndrome through questionnaire survey of a cohort of families. The Short Sensory Profile, Vineland Adaptive Behavior Scale, and Developmental Behaviour Checklist were distributed to 30 families; 16 were returned anonymously. Atypical sensory behaviors were identified in a large proportion (62.5%). Children reported as being more anxious showed greater sensitivity to auditory stimuli, U(14) 11, P = .026. This is consistent with recent recognition of more extensive disease neurocognitive effects in Opsoclonus myoclonus syndrome. Further research is needed to increase understanding of the complex pathology of this disease and to provide indicators for sensory and behavioral as well as pharmacological interventions. PMID- 26994072 TI - Phenobarbital and Insulin Reciprocate Activation of the Nuclear Receptor Constitutive Androstane Receptor through the Insulin Receptor. AB - Phenobarbital (PB) antagonized insulin to inactivate the insulin receptor and attenuated the insulin receptor downstream protein kinase B (AKT)-forkhead box protein O1 and extracellular signal-regulated kinase 1/2 signals in mouse primary hepatocytes and HepG2 cells. Hepatic AKT began dephosphorylation in an early stage of PB treatment, and blood glucose levels transiently increased in both wild-type and constitutive androstane receptor (CAR) knockout (KO) mice. On the other hand, blood glucose levels increased in wild-type mice, but not KO mice, in later stages of PB treatment. As a result, PB, acting as an insulin receptor antagonist, elicited CAR-independent increases and CAR-dependent decreases of blood glucose levels at these different stages of treatment, respectively. Reciprocally, insulin activation of the insulin receptor repressed CAR activation and induction of its target CYP2B6 gene in HepG2 cells. Thus, PB and insulin cross-talk through the insulin receptor to regulate glucose and drug metabolism reciprocally. PMID- 26994073 TI - Construction of Nontoxigenic Mutants of Nonproteolytic Clostridium botulinum NCTC 11219 by Insertional Mutagenesis and Gene Replacement. AB - Group II nonproteolytic Clostridium botulinum (gIICb) strains are an important concern for the safety of minimally processed ready-to-eat foods, because they can grow and produce botulinum neurotoxin during refrigerated storage. The principles of control of gIICb by conventional food processing and preservation methods have been well investigated and translated into guidelines for the food industry; in contrast, the effectiveness of emerging processing and preservation techniques has been poorly documented. The reason is that experimental studies with C. botulinum are cumbersome because of biosafety and biosecurity concerns. In the present work, we report the construction of two nontoxigenic derivatives of the type E gIICb strain NCTC 11219. In the first strain, the botulinum toxin gene (bont/E) was insertionally inactivated with a retargeted intron using the ClosTron system. In the second strain, bont/E was exchanged for an erythromycin resistance gene using a new gene replacement strategy that makes use of pyrE as a bidirectional selection marker. Growth under optimal and stressed conditions, sporulation efficiency, and spore heat resistance of the mutants were unaltered, except for small differences in spore heat resistance at 70 degrees C and in growth at 2.3% NaCl. The mutants described in this work provide a safe alternative for basic research as well as for food challenge and process validation studies with gIICb. In addition, this work expands the clostridial genetic toolbox with a new gene replacement method that can be applied to replace any gene in gIICb and other clostridia. IMPORTANCE: The nontoxigenic mutants described in this work provide a safe alternative for basic research as well as for food challenge and process validation studies with psychrotrophic Clostridium botulinum In addition, this work expands the clostridial genetic toolbox with a new gene replacement method that can be applied to replace any gene in clostridia. PMID- 26994074 TI - Vacuolar H+-ATPase Protects Saccharomyces cerevisiae Cells against Ethanol Induced Oxidative and Cell Wall Stresses. AB - During fermentation, increased ethanol concentration is a major stress for yeast cells. Vacuolar H(+)-ATPase (V-ATPase), which plays an important role in the maintenance of intracellular pH homeostasis through vacuolar acidification, has been shown to be required for tolerance to straight-chain alcohols, including ethanol. Since ethanol is known to increase membrane permeability to protons, which then promotes intracellular acidification, it is possible that the V-ATPase is required for recovery from alcohol-induced intracellular acidification. In this study, we show that the effects of straight-chain alcohols on membrane permeabilization and acidification of the cytosol and vacuole are strongly dependent on their lipophilicity. These findings suggest that the membrane permeabilizing effect of straight-chain alcohols induces cytosolic and vacuolar acidification in a lipophilicity-dependent manner. Surprisingly, after ethanol challenge, the cytosolic pH in Deltavma2 and Deltavma3 mutants lacking V-ATPase activity was similar to that of the wild-type strain. It is therefore unlikely that the ethanol-sensitive phenotype of vma mutants resulted from severe cytosolic acidification. Interestingly, the vma mutants exposed to ethanol exhibited a delay in cell wall remodeling and a significant increase in intracellular reactive oxygen species (ROS). These findings suggest a role for V ATPase in the regulation of the cell wall stress response and the prevention of endogenous oxidative stress in response to ethanol. IMPORTANCE: The yeast Saccharomyces cerevisiae has been widely used in the alcoholic fermentation industry. Among the environmental stresses that yeast cells encounter during the process of alcoholic fermentation, ethanol is a major stress factor that inhibits yeast growth and viability, eventually leading to fermentation arrest. This study provides evidence for the molecular mechanisms of ethanol tolerance, which is a desirable characteristic for yeast strains used in alcoholic fermentation. The results revealed that straight-chain alcohols induced cytosolic and vacuolar acidification through their membrane-permeabilizing effects. Contrary to expectations, a role for V-ATPase in the regulation of the cell wall stress response and the prevention of endogenous oxidative stress, but not in the maintenance of intracellular pH, seems to be important for protecting yeast cells against ethanol stress. These findings will expand our understanding of the mechanisms of ethanol tolerance and provide promising clues for the development of ethanol-tolerant yeast strains. PMID- 26994075 TI - Wolbachia Modulates Lipid Metabolism in Aedes albopictus Mosquito Cells. AB - Certain strains of the intracellular endosymbiont Wolbachia can strongly inhibit or block the transmission of viruses such as dengue virus (DENV) by Aedes mosquitoes, and the mechanisms responsible are still not well understood. Direct infusion and liquid chromatography-Fourier transform ion cyclotron resonance (FT ICR) mass spectrometry-based lipidomics analyses were conducted using Aedes albopictus Aa23 cells that were infected with the wMel and wMelPop strains of Wolbachia in comparison to uninfected Aa23-T cells. Substantial shifts in the cellular lipid profile were apparent in the presence of Wolbachia Most significantly, almost all sphingolipid classes were depleted, and some reductions in diacylglycerols and phosphatidylcholines were also observed. These lipid classes have previously been shown to be selectively enriched in DENV-infected mosquito cells, suggesting that Wolbachia may produce a cellular lipid environment that is antagonistic to viral replication. The data improve our understanding of the intracellular interactions between Wolbachia and mosquitoes. IMPORTANCE: Mosquitoes transmit a variety of important viruses to humans, such as dengue virus and Zika virus. Certain strains of the intracellular bacterial genus called Wolbachia found in or introduced into mosquitoes can block the transmission of viruses, including dengue virus, but the mechanisms responsible are not well understood. We found substantial shifts in the cellular lipid profiles in the presence of these bacteria. Some lipid classes previously shown to be enriched in dengue virus-infected mosquito cells were depleted in the presence of Wolbachia, suggesting that Wolbachia may produce a cellular lipid environment that inhibits mosquito-borne viruses. PMID- 26994076 TI - Environmental Metabolomics of the Tomato Plant Surface Provides Insights on Salmonella enterica Colonization. AB - Foodborne illness-causing enteric bacteria are able to colonize plant surfaces without causing infection. We lack an understanding of how epiphytic persistence of enteric bacteria occurs on plants, possibly as an adaptive transit strategy to maximize chances of reentering herbivorous hosts. We used tomato (Solanum lycopersicum) cultivars that have exhibited differential susceptibilities to Salmonella enterica colonization to investigate the influence of plant surface compounds and exudates on enteric bacterial populations. Tomato fruit, shoot, and root exudates collected at different developmental stages supported growth of S. enterica to various degrees in a cultivar- and plant organ-dependent manner. S. enterica growth in fruit exudates of various cultivars correlated with epiphytic growth data (R(2) = 0.504; P = 0.006), providing evidence that plant surface compounds drive bacterial colonization success. Chemical profiling of tomato surface compounds with gas chromatography-time of flight mass spectrometry (GC TOF-MS) provided valuable information about the metabolic environment on fruit, shoot, and root surfaces. Hierarchical cluster analysis of the data revealed quantitative differences in phytocompounds among cultivars and changes over a developmental course and by plant organ (P < 0.002). Sugars, sugar alcohols, and organic acids were associated with increased S. enterica growth, while fatty acids, including palmitic and oleic acids, were negatively correlated. We demonstrate that the plant surface metabolite landscape has a significant impact on S. enterica growth and colonization efficiency. This environmental metabolomics approach provides an avenue to understand interactions between human pathogens and plants that could lead to strategies to identify or breed crop cultivars for microbiologically safer produce. IMPORTANCE: In recent years, fresh produce has emerged as a leading food vehicle for enteric pathogens. Salmonella contaminated tomatoes represent a recurrent human pathogen-plant commodity pair. We demonstrate that Salmonella can utilize tomato surface compounds and exudates for growth. Surface metabolite profiling revealed that the types and amounts of compounds released to the plant surface differ by cultivar, plant developmental stage, and plant organ. Differences in exudate profiles explain some of the variability in Salmonella colonization susceptibility seen among tomato cultivars. Certain medium- and long-chain fatty acids were associated with restricted Salmonella growth, while sugars, sugar alcohols, and organic acids correlated with larger Salmonella populations. These findings uncover the possibility of selecting crop varieties based on characteristics that impair foodborne pathogen growth for enhanced safety of fresh produce. PMID- 26994077 TI - Silica-Induced Protein (Sip) in Thermophilic Bacterium Thermus thermophilus Responds to Low Iron Availability. AB - Thermus thermophilus HB8 expresses silica-induced protein (Sip) when cultured in medium containing supersaturated silicic acids. Using genomic information, Sip was identified as a Fe(3+)-binding ABC transporter. Detection of a 1-kb hybridized band in Northern analysis revealed that sip transcription is monocistronic and that sip has its own terminator and promoter. The sequence of the sip promoter showed homology with that of the sigma(A)-dependent promoter, which is known as a housekeeping promoter in HB8. Considering that sip is transcribed when supersaturated silicic acids are added, the existence of a repressor is presumed. DNA microarray analysis suggested that supersaturated silicic acids and iron deficiency affect Thermus cells similarly, and enhanced sip transcription was detected under both conditions. This suggested that sip transcription was initiated by iron deficiency and that the ferric uptake regulator (Fur) controlled the transcription. Three Fur gene homologues (TTHA0255, TTHA0344, and TTHA1292) have been annotated in the HB8 genome, and electrophoretic mobility shift assays revealed that the TTHA0344 product interacts with the sip promoter region. In medium containing supersaturated silicic acids, free Fe(3+) levels were decreased due to Fe(3+) immobilization on colloidal silica. This suggests that, because Fe(3+) ions are captured by colloidal silica in geothermal water, Thermus cells are continuously exposed to the risk of iron deficiency. Considering that Sip is involved in iron acquisition, Sip production may be a strategy to survive under conditions of low iron availability in geothermal water. IMPORTANCE: The thermophilic bacterium Thermus thermophilus HB8 produces silica-induced protein (Sip) in the presence of supersaturated silicic acids. Sip has homology with iron-binding ABC transporter; however, the mechanism by which Sip expression is induced by silicic acids remains unexplained. We demonstrate that Sip captures iron and its transcription is regulated by the repressor ferric uptake regulator (Fur). This implies that Sip is expressed with iron deficiency. In addition, it is suggested that negatively charged colloidal silica in supersaturated solution absorbs Fe(3+) ions and decreases iron availability. Considering that geothermal water contains ample silicic acids, it is suggested that thermophilic bacteria are always facing iron starvation. Sip production may be a strategy for surviving under conditions of low iron availability in geothermal water. PMID- 26994078 TI - Ecophysiological Distinctions of Haloarchaea from a Hypersaline Antarctic Lake as Determined by Metaproteomics. AB - Deep Lake in the Vestfold Hills is hypersaline and the coldest system in Antarctica known to support microbial growth (temperatures as low as -20 degrees C). It represents a strong experimental model because the lake supports a low complexity community of haloarchaea, with the three most abundant species totaling ~72%. Moreover, the dominant haloarchaea are cultivatable, and their genomes are sequenced. Here we use metaproteomics linked to metagenome data and the genome sequences of the isolates to characterize the main pathways, trophic strategies, and interactions associated with resource utilization. The dominance of the most abundant member, Halohasta litchfieldiae, appears to be predicated on competitive utilization of substrates (e.g., starch, glycerol, and dihydroxyacetone) produced by Dunaliella, the lake's primary producer, while also possessing diverse mechanisms for acquiring nitrogen and phosphorus. The second most abundant member, strain DL31, is proficient in degrading complex proteinaceous matter. Hht. litchfieldiae and DL31 are inferred to release labile substrates that are utilized by Halorubrum lacusprofundi, the third most abundant haloarchaeon in Deep Lake. The study also linked genome variation to specific protein variants or distinct genetic capacities, thereby identifying strain-level variation indicative of specialization. Overall, metaproteomics revealed that rather than functional differences occurring at different lake depths or through size partitioning, the main lake genera possess major trophic distinctions, and phylotypes (e.g., strains of Hht. litchfieldiae) exhibit a more subtle level of specialization. This study highlights the extent to which the lake supports a relatively uniform distribution of taxa that collectively possess the genetic capacity to effectively exploit available nutrients throughout the lake. IMPORTANCE: Life on Earth has evolved to colonize a broad range of temperatures, but most of the biosphere (~85%) exists at low temperatures (<=5 degrees C). By performing unique roles in biogeochemical cycles, environmental microorganisms perform functions that are critical for the rest of life on Earth to survive. Cold environments therefore make a particularly important contribution to maintaining healthy, stable ecosystems. Here we describe the main physiological traits of the dominant microorganisms that inhabit Deep Lake in Antarctica, the coldest aquatic environment known to support life. The hypersaline system enables the growth of halophilic members of the Archaea: haloarchaea. By analyzing proteins of samples collected from the water column, we determined the functions that the haloarchaea were likely to perform. This study showed that the dominant haloarchaea possessed distinct lifestyles yet formed a uniform community throughout the lake that was collectively adept at using available light energy and diverse organic substrates for growth. PMID- 26994079 TI - Inactivation of Acanthamoeba spp. and Other Ocular Pathogens by Application of Cold Atmospheric Gas Plasma. AB - Currently there are estimated to be approximately 3.7 million contact lens wearers in the United Kingdom and 39.2 million in North America. Contact lens wear is a major risk factor for developing an infection of the cornea known as keratitis due to poor lens hygiene practices. While there is an international standard for testing disinfection methods against bacteria and fungi (ISO 14729), no such guidelines exist for the protozoan Acanthamoeba, which causes a potentially blinding keratitis most commonly seen in contact lens wearers, and as a result, many commercially available disinfecting solutions show incomplete disinfection after 6 and 24 h of exposure. Challenge test assays based on international standard ISO 14729 were used to determine the antimicrobial activity of cold atmospheric gas plasma (CAP) against Pseudomonas aeruginosa, Candida albicans, and trophozoites and cysts of Acanthamoeba polyphaga and Acanthamoeba castellanii P. aeruginosa and C. albicans were completely inactivated in 0.5 min and 2 min, respectively, and trophozoites of A. polyphaga and A. castellanii were completely inactivated in 1 min and 2 min, respectively. Furthermore, for the highly resistant cyst stage of both species, complete inactivation was achieved after 4 min of exposure to CAP. This study demonstrates that the CAP technology is highly effective against bacterial, fungal, and protozoan pathogens. The further development of this technology has enormous potential, as this approach is able to deliver the complete inactivation of ocular pathogens in minutes, in contrast to commercial multipurpose disinfecting solutions that require a minimum of 6 h. PMID- 26994080 TI - A Nonautochthonous U.S. Strain of Vibrio parahaemolyticus Isolated from Chesapeake Bay Oysters Caused the Outbreak in Maryland in 2010. AB - In the summer of 2010, Vibrio parahaemolyticus caused an outbreak in Maryland linked to the consumption of oysters. Strains isolated from both stool and oyster samples were indistinguishable by pulsed-field gel electrophoresis (PFGE). However, the oysters contained other potentially pathogenic V. parahaemolyticus strains exhibiting different PFGE patterns. In order to assess the identity, genetic makeup, relatedness, and potential pathogenicity of the V. parahaemolyticus strains, we sequenced 11 such strains (2 clinical strains and 9 oyster strains). We analyzed these genomes by in silico multilocus sequence typing (MLST) and determined their phylogeny using a whole-genome MLST (wgMLST) analysis. Our in silico MLST analysis identified six different sequence types (STs) (ST8, ST676, ST810, ST811, ST34, and ST768), with both of the clinical and four of the oyster strains being identified as belonging to ST8. Using wgMLST, we showed that the ST8 strains from clinical and oyster samples were nearly indistinguishable and belonged to the same outbreak, confirming that local oysters were the source of the infections. The remaining oyster strains were genetically diverse, differing in >3,000 loci from the Maryland ST8 strains. eBURST analysis comparing these strains with strains of other STs available at the V. parahaemolyticus MLST website showed that the Maryland ST8 strains belonged to a clonal complex endemic to Asia. This indicates that the ST8 isolates from clinical and oyster sources were likely not endemic to Maryland. Finally, this study demonstrates the utility of whole-genome sequencing (WGS) and associated analyses for source-tracking investigations. IMPORTANCE: Vibrio parahaemolyticus is an important foodborne pathogen and the leading cause of bacterial infections in the United States associated with the consumption of seafood. In the summer of 2010, Vibrio parahaemolyticus caused an outbreak in Maryland linked to oyster consumption. Strains isolated from stool and oyster samples were indistinguishable by pulsed-field gel electrophoresis (PFGE). The oysters also contained other potentially pathogenic V. parahaemolyticus strains with different PFGE patterns. Since their identity, genetic makeup, relatedness, and potential pathogenicity were unknown, their genomes were determined by using next-generation sequencing. Whole-genome sequencing (WGS) analysis by whole genome multilocus sequence typing (wgMLST) allowed (i) identification of clinical and oyster strains with matching PFGE profiles as belonging to ST8, (ii) determination of oyster strain diversity, and (iii) identification of the clinical strains as belonging to a clonal complex (CC) described only in Asia. Finally, WGS and associated analyses demonstrated their utility for trace-back investigations. PMID- 26994081 TI - A Chemotaxis Receptor Modulates Nodulation during the Azorhizobium caulinodans Sesbania rostrata Symbiosis. AB - Azorhizobium caulinodans ORS571 is a free-living nitrogen-fixing bacterium which can induce nitrogen-fixing nodules both on the root and the stem of its legume host Sesbania rostrata This bacterium, which is an obligate aerobe that moves by means of a polar flagellum, possesses a single chemotaxis signal transduction pathway. The objective of this work was to examine the role that chemotaxis and aerotaxis play in the lifestyle of the bacterium in free-living and symbiotic conditions. In bacterial chemotaxis, chemoreceptors sense environmental changes and transmit this information to the chemotactic machinery to guide motile bacteria to preferred niches. Here, we characterized a chemoreceptor of A. caulinodans containing an N-terminal PAS domain, named IcpB. IcpB is a soluble heme-binding protein that localized at the cell poles. An icpB mutant strain was impaired in sensing oxygen gradients and in chemotaxis response to organic acids. Compared to the wild-type strain, the icpB mutant strain was also affected in the production of extracellular polysaccharides and impaired in flocculation. When inoculated alone, the icpB mutant induced nodules on S. rostrata, but the nodules formed were smaller and had reduced N2-fixing activity. The icpB mutant failed to nodulate its host when inoculated competitively with the wild-type strain. Together, the results identify chemotaxis and sensing of oxygen by IcpB as key regulators of the A. caulinodans-S. rostrata symbiosis. IMPORTANCE: Bacterial chemotaxis has been implicated in the establishment of various plant-microbe associations, including that of rhizobial symbionts with their legume host. The exact signal(s) detected by the motile bacteria that guide them to their plant hosts remain poorly characterized. Azorhizobium caulinodans ORS571 is a diazotroph that is a motile and chemotactic rhizobial symbiont of Sesbania rostrata, where it forms nitrogen-fixing nodules on both the roots and the stems of the legume host. We identify here a chemotaxis receptor sensing oxygen in A. caulinodans that is critical for nodulation and nitrogen fixation on the stems and roots of S. rostrata These results identify oxygen sensing and chemotaxis as key regulators of the A. caulinodans-S. rostrata symbiosis. PMID- 26994082 TI - Persistence of Influenza A (H1N1) Virus on Stainless Steel Surfaces. AB - As annual influenza epidemics continue to cause significant morbidity and economic burden, an understanding of viral persistence and transmission is critical for public health officials and health care workers to better protect patients and their family members from infection. The infectivity and persistence of two influenza A (H1N1) virus strains (A/New Caledonia/20/1999 and A/Brisbane/59/2007) on stainless steel (SS) surfaces were evaluated using three different surface matrices (2% fetal bovine serum, 5 mg/ml mucin, and viral medium) under various absolute humidity conditions (4.1 * 10(5) mPa, 6.5 * 10(5) mPa, 7.1 * 10(5) mPa, 11.4 * 10(5) mPa, 11.2 * 10(5) mPa, and 17.9 * 10(5) mPa) for up to 7 days. Influenza A virus was deposited onto SS coupons (7.07 cm(2)) and recovered by agitation and sonication in viral medium. Viral persistence was quantified using a tissue culture-based enzyme-linked immunosorbent assay (ELISA) to determine the median (50%) tissue culture infective dose (TCID50) of infectious virus per coupon. Overall, both strains of influenza A virus remained infectious on SS coupons, with an approximate 2 log10 loss over 7 days. Factors that influenced viral persistence included absolute humidity, strain-absolute humidity interaction, and time (P <= 0.01). Further studies on the transfer of influenza A virus from fomites by hand and the impact of inanimate surface contamination on transmission should be performed, as this study demonstrates prolonged persistence on nonporous surfaces. IMPORTANCE: This study tested the ability of two influenza A (H1N1) virus strains to persist and remain infectious on stainless steel surfaces under various environmental conditions. It demonstrated that influenza A (H1N1) viruses can persist and remain infectious on stainless steel surfaces for 7 days. Additional studies should be conducted to assess the role played by contaminated surfaces in the transmission of influenza A virus. PMID- 26994083 TI - Variability of the Sheep Lung Microbiota. AB - Sequencing technologies have recently facilitated the characterization of bacterial communities present in lungs during health and disease. However, there is currently a dearth of information concerning the variability of such data in health both between and within subjects. This study seeks to examine such variability using healthy adult sheep as our model system. Protected specimen brush samples were collected from three spatially disparate segmental bronchi of six adult sheep (age, 20 months) on three occasions (day 0, 1 month, and 3 months). To further explore the spatial variability of the microbiotas, more extensive brushing samples (n = 16) and a throat swab were taken from a separate sheep. The V2 and V3 hypervariable regions of the bacterial 16S rRNA genes were amplified and sequenced via Illumina MiSeq. DNA sequences were analyzed using the mothur software package. Quantitative PCR was performed to quantify total bacterial DNA. Some sheep lungs contained dramatically different bacterial communities at different sampling sites, whereas in others, airway microbiotas appeared similar across the lung. In our spatial variability study, we observed clustering related to the depth within the lung from which samples were taken. Lung depth refers to increasing distance from the glottis, progressing in a caudal direction. We conclude that both host influence and local factors have impacts on the composition of the sheep lung microbiota. IMPORTANCE: Until recently, it was assumed that the lungs were a sterile environment which was colonized by microbes only during disease. However, recent studies using sequencing technologies have found that there is a small population of bacteria which exists in the lung during health, referred to as the "lung microbiota." In this study, we characterize the variability of the lung microbiotas of healthy sheep. Sheep not only are economically important animals but also are often used as large animal models of human respiratory disease. We conclude that, while host influence does play a role in dictating the types of microbes which colonize the airways, it is clear that local factors also play an important role in this regard. Understanding the nature and influence of these factors will be key to understanding the variability in, and functional relevance of, the lung microbiota. PMID- 26994084 TI - Superinfection Exclusion of the Ruminant Pathogen Anaplasma marginale in Its Tick Vector Is Dependent on the Time between Exposures to the Strains. AB - The remarkable genetic diversity of vector-borne pathogens allows for the establishment of superinfection in the mammalian host. To have a long-term impact on population strain structure, the introduced strains must also be transmitted by a vector population that has been exposed to the existing primary strain. The sequential exposure of the vector to multiple strains frequently prevents establishment of the second strain, a phenomenon termed superinfection exclusion. As a consequence, superinfection exclusion may greatly limit genetic diversity in the host population, which is difficult to reconcile with the high degree of genetic diversity maintained among vector-borne pathogens. Using Anaplasma marginale, a tick-borne bacterial pathogen of ruminants, we hypothesized that superinfection exclusion is temporally dependent and that longer intervals between strain exposures allow successful acquisition and transmission of a superinfecting strain. To test this hypothesis, we sequentially exposed Dermacentor andersoni ticks to two readily tick-transmissible strains of A. marginale The tick feedings were either immediately sequential or 28 days apart. Ticks were allowed to transmission feed and were individually assessed to determine if they were infected with one or both strains. The second strain was excluded from the tick when the exposure interval was brief but not when it was prolonged. Midguts and salivary glands of individual ticks were superinfected and transmission of both strains occurred only when the exposure interval was prolonged. These findings indicate that superinfection exclusion is temporally dependent, which helps to account for the differences in pathogen strain structure in tropical compared to temperate regions. IMPORTANCE: Many vector borne pathogens have marked genetic diversity, which influences pathogen traits such as transmissibility and virulence. The most successful strains are those that are preferentially transmitted by the vector. However, the factors that determine successful transmission of a particular strain are unknown. In the case of intracellular, bacterial, tick-borne pathogens, one potential factor is superinfection exclusion, in which colonization of ticks by the first strain of a pathogen it encounters prevents the transmission of a second strain. Using A. marginale, the most prevalent tick-borne pathogen of cattle worldwide, and its natural tick vector, we determined that superinfection exclusion occurs when the time between exposures to two strains is brief but not when it is prolonged. These findings suggest that superinfection exclusion may influence strain transmission in temperate regions, where tick activity is limited by season, but not in tropical regions, where ticks are active for long periods. PMID- 26994085 TI - Virulence Gene-Associated Mutant Bacterial Colonies Generate Differentiating Two Dimensional Laser Scatter Fingerprints. AB - In this study, we investigated whether a laser scatterometer designated BARDOT (bacterial rapid detection using optical scattering technology) could be used to directly screen colonies of Listeria monocytogenes, a model pathogen, with mutations in several known virulence genes, including the genes encoding Listeria adhesion protein (LAP; lap mutant), internalin A (DeltainlA strain), and an accessory secretory protein (DeltasecA2 strain). Here we show that the scatter patterns of lap mutant, DeltainlA, and DeltasecA2 colonies were markedly different from that of the wild type (WT), with >95% positive predictive values (PPVs), whereas for the complemented mutant strains, scatter patterns were restored to that of the WT. The scatter image library successfully distinguished the lap mutant and DeltainlA mutant strains from the WT in mixed-culture experiments, including a coinfection study using the Caco-2 cell line. Among the biophysical parameters examined, the colony height and optical density did not reveal any discernible differences between the mutant and WT strains. We also found that differential LAP expression in L. monocytogenes serotype 4b strains also affected the scatter patterns of the colonies. The results from this study suggest that BARDOT can be used to screen and enumerate mutant strains separately from the WT based on differential colony scatter patterns. IMPORTANCE: In studies of microbial pathogenesis, virulence-encoding genes are routinely disrupted by deletion or insertion to create mutant strains. Screening of mutant strains is an arduous process involving plating on selective growth media, replica plating, colony hybridization, DNA isolation, and PCR or immunoassays. We applied a noninvasive laser scatterometer to differentiate mutant bacterial colonies from WT colonies based on forward optical scatter patterns. This study demonstrates that BARDOT can be used as a novel, label-free, real-time tool to aid researchers in screening virulence gene-associated mutant colonies during microbial pathogenesis, coinfection, and genetic manipulation studies. PMID- 26994086 TI - Two Bacterial Genera, Sodalis and Rickettsia, Associated with the Seal Louse Proechinophthirus fluctus (Phthiraptera: Anoplura). AB - Roughly 10% to 15% of insect species host heritable symbiotic bacteria known as endosymbionts. The lice parasitizing mammals rely on endosymbionts to provide essential vitamins absent in their blood meals. Here, we describe two bacterial associates from a louse, Proechinophthirus fluctus, which is an obligate ectoparasite of a marine mammal. One of these is a heritable endosymbiont that is not closely related to endosymbionts of other mammalian lice. Rather, it is more closely related to endosymbionts of the genus Sodalis associated with spittlebugs and feather-chewing bird lice. Localization and vertical transmission of this endosymbiont are also more similar to those of bird lice than to those of other mammalian lice. The endosymbiont genome appears to be degrading in symbiosis; however, it is considerably larger than the genomes of other mammalian louse endosymbionts. These patterns suggest the possibility that this Sodalis endosymbiont might be recently acquired, replacing a now-extinct, ancient endosymbiont. From the same lice, we also identified an abundant bacterium belonging to the genus Rickettsia that is closely related to Rickettsia ricketsii, a human pathogen vectored by ticks. No obvious masses of the Rickettsia bacterium were observed in louse tissues, nor did we find any evidence of vertical transmission, so the nature of its association remains unclear. IMPORTANCE: Many insects are host to heritable symbiotic bacteria. These heritable bacteria have been identified from numerous species of parasitic lice. It appears that novel symbioses have formed between lice and bacteria many times, with new bacterial symbionts potentially replacing existing ones. However, little was known about the symbionts of lice parasitizing marine mammals. Here, we identified a heritable bacterial symbiont in lice parasitizing northern fur seals. This bacterial symbiont appears to have been recently acquired by the lice. The findings reported here provide insights into how new symbioses form and how this lifestyle is shaping the symbiont genome. PMID- 26994088 TI - Enhanced Understanding of the Levels of Palliative Care in Pharmacy Students Through Participating in Clinical Training in Hospitals. AB - OBJECTIVE: A palliative care knowledge survey was conducted involving pharmacy students to examine their perceived usefulness and the educational effect of clinical training in hospitals. METHODS: A questionnaire sheet was distributed to fifth-year pharmacy students before and after clinical training. The questionnaire consisted of questions to clarify the details of palliative care related training in hospitals and students' knowledge of such care. The respondents were divided into 2 groups: those who participated in palliative care team (PCT) rounds (group A: 57) and those who did not (group B: 57). RESULTS: The mean total correct answer rate markedly increased after training in group A, from 37.9 to 47.1% (P < .01). Such an increase was also observed in the domains of philosophy and pain in this group ( P < .01). In contrast, group B did not show differences in the mean correct answer rate between before and after training; there was no significant increase in the rate in any domain. CONCLUSION: Pharmacy students' knowledge was enhanced by participating in the PCT, confirming the usefulness of such participation during training as part of palliative care education. PMID- 26994087 TI - Novel Cupriavidus Strains Isolated from Root Nodules of Native Uruguayan Mimosa Species. AB - The large legume genus Mimosa is known to be associated with both alphaproteobacterial and betaproteobacterial symbionts, depending on environment and plant taxonomy, e.g., Brazilian species are preferentially nodulated by Burkholderia, whereas those in Mexico are associated with alphaproteobacterial symbionts. Little is known, however, about the symbiotic preferences of Mimosa spp. at the southern subtropical limits of the genus. In the present study, rhizobia were isolated from field-collected nodules from Mimosa species that are native to a region in southern Uruguay. Phylogenetic analyses of sequences of the 16S rRNA, recA, and gyrB core genome and the nifH and nodA symbiosis-essential loci confirmed that all the isolates belonged to the genus Cupriavidus However, none were in the well-described symbiotic species C. taiwanensis, but instead they were closely related to other species, such as C. necator, and to species not previously known to be symbiotic (or diazotrophic), such as C. basilensis and C. pinatubonensis Selection of these novel Cupriavidus symbionts by Uruguayan Mimosa spp. is most likely due to their geographical separation from their Brazilian cousins and to the characteristics of the soils in which they were found. IMPORTANCE: With the aim of exploring the diversity of rhizobia associated with native Mimosa species, symbionts were isolated from root nodules on five Mimosa species that are native to a region in southern Uruguay, Sierra del Abra de Zabaleta. In contrast to data obtained in the major centers of diversification of the genus Mimosa, Brazil and Mexico, where it is mainly associated with Burkholderia and Rhizobium/Ensifer, respectively, the present study has shown that all the isolated symbiotic bacteria belonged to the genus Cupriavidus Interestingly, none of nodules contained bacteria belonging to the well-described symbiotic species C. taiwanensis, but instead they were related to other Cupriavidus species such as C. necator and C. pinatubonensis These data suggest the existence of a higher diversity within beta-rhizobial Cupriavidus than was previously suspected, and that Mimosa spp. from Sierra del Abra de Zabaleta, may be natural reservoirs for novel rhizobia. PMID- 26994089 TI - A randomized clinical trial comparing ritonavir-boosted lopinavir versus raltegravir each with tenofovir plus emtricitabine for post-exposure prophylaxis for HIV infection. AB - OBJECTIVES: The objective of this study was to assess post-exposure prophylaxis (PEP) non-completion at day 28, comparing two regimens. METHODS: A prospective, open, randomized clinical trial was conducted at a tertiary hospital in Barcelona, Spain. Individuals attending the emergency room because of potential sexual exposure to HIV were randomized to tenofovir disoproxil/emtricitabine (245/200 mg) plus either ritonavir-boosted lopinavir (400/100 mg) or raltegravir (400 mg). The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse events and rate of seroconversions. This study was registered in ClinicalTrials.gov: NCT01576731. RESULTS: One-hundred-and twenty-one individuals were randomized to receive ritonavir-boosted lopinavir and 122 to raltegravir (n = 243). PEP non-completion at day 28 was 43% with no significant difference between arms. We performed a modified ITT analysis including only those patients who attended on day 1 (n = 191). PEP non-completion in this subgroup was higher in the ritonavir-boosted lopinavir arm than in the raltegravir arm (34.6% versus 20.4%, P = 0.04), as was the number of patients lost to follow-up at day 28 (32.6% versus 21.6%, P = 0.08) and the proportion of patients with low adherence (49.2% versus 30.8%, P = 0.03). Adverse events were significantly more common in the ritonavir-boosted lopinavir arm (73.4% versus 60.2%, P = 0.007). There was an HIV seroconversion at day 90 in the raltegravir arm in a patient who had multiple potential sexual risk exposures before and after receiving PEP. CONCLUSIONS: Although we found no differences between arms regarding PEP non-completion, poor adherence and adverse events were significantly higher in patients allocated to tenofovir disoproxil/emtricitabine plus ritonavir-boosted lopinavir. These data support the use of raltegravir as the preferred third drug in current PEP recommendations. PMID- 26994090 TI - Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial. AB - OBJECTIVES: Empirical fluoroquinolone therapy is widely used in treating complicated urinary tract infections (cUTIs), even in areas of high fluoroquinolone resistance. While it is believed that high antibiotic concentrations in urine might be sufficient to overcome and effectively treat infections caused by resistant bacteria, clinical trial data validating this assumption are limited. This post hoc analysis evaluated the efficacy of ceftolozane/tazobactam versus levofloxacin in the subgroup of patients with cUTIs caused by levofloxacin-resistant pathogens in a randomized, controlled trial (NCT01345929/NCT01345955). METHODS: Hospitalized adults with cUTI/pyelonephritis were randomized to 7 days of 1.5 g of ceftolozane/tazobactam every 8 h or 750 mg of levofloxacin once daily, before availability of culture and susceptibility data. A composite of microbiological eradication and clinical cure 5 to 9 days post-therapy was assessed in the microbiological modified ITT (mMITT; n = 800) and microbiologically evaluable (ME; n = 694) populations. RESULTS: In the mMITT population, there were 212 patients (26.5%) with at least one baseline uropathogen that was resistant to levofloxacin. The majority of uropathogens in this subgroup were Enterobacteriaceae (n = 186) that were susceptible to ceftolozane/tazobactam [MIC <=2 mg/L, 88.7% (165/186)]. Among patients with levofloxacin-resistant pathogens, ceftolozane/tazobactam demonstrated significantly higher composite cure rates than levofloxacin in both the mMITT [60.0% (60/100) versus 39.3% (44/112); 95% CI for the treatment difference, 7.2% 33.2%] and ME [64.0% (57/89) versus 43.4% (43/99); 95% CI for the treatment difference, 6.3%-33.7%] populations, respectively. CONCLUSIONS: High urinary levels of levofloxacin did not reliably cure cUTIs. Seven day treatment with ceftolozane/tazobactam was more effective than high-dose levofloxacin treatment in patients with cUTI caused by levofloxacin-resistant bacteria, and it may be an alternative treatment in settings of increased fluoroquinolone resistance. PMID- 26994092 TI - NEED FOR INDIVIDUAL CANCER RISK ESTIMATES IN X-RAY AND NUCLEAR MEDICINE IMAGING. AB - To facilitate the justification of an X-ray or nuclear medicine investigation and for informing patients, it is desirable that the individual patient's radiation dose and potential cancer risk can be prospectively assessed and documented. The current dose-reporting is based on effective dose, which ignores body size and does not reflect the strong dependence of risk on the age at exposure. Risk estimations should better be done through individual organ dose assessments, which need careful exposure characterisation as well as anatomical description of the individual patient. In nuclear medicine, reference biokinetic models should also be replaced with models describing individual physiological states and biokinetics. There is a need to adjust population-based cancer risk estimates to the possible risk of leukaemia and solid tumours for the individual depending on age and gender. The article summarises reasons for individual cancer risk estimates and gives examples of methods and results of such estimates. PMID- 26994091 TI - A randomized clinical trial comparing ritonavir-boosted lopinavir versus maraviroc each with tenofovir plus emtricitabine for post-exposure prophylaxis for HIV infection. AB - OBJECTIVES: The objective of this study was to assess post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus maraviroc, both with tenofovir disoproxil/emtricitabine as the backbone. METHODS: We conducted a prospective, open, randomized clinical trial. Individuals attending the emergency room because of potential sexual exposure to HIV and who met criteria for receiving PEP were randomized to one of two groups: tenofovir disoproxil/emtricitabine (245/200 mg) once daily plus either ritonavir-boosted lopinavir (400/100 mg) or maraviroc (300 mg) twice daily. Five follow-up visits were scheduled for days 1, 10, 28, 90 and 180. The primary endpoint was PEP non completion at day 28. Secondary endpoints were adherence, adverse events and rate of seroconversions. This study was registered in ClinicalTrials.gov: NCT01533272. RESULTS: One-hundred-and-seventeen individuals were randomized to receive ritonavir-boosted lopinavir and 120 to maraviroc (n = 237). PEP non-completion at day 28 was 38% (n = 89), with significant differences between arms [ritonavir boosted lopinavir 44% (n = 51) versus maraviroc 32% (n = 38), P = 0.05]. We performed a modified ITT analysis including only those patients who attended on day 1 (n = 182). PEP non-completion in this subgroup was also significantly higher in the ritonavir-boosted lopinavir arm (27% versus 13%, P = 0.004). The proportion of patients with low adherence was similar between arms (52% versus 47%, P = 0.56). Adverse events were reported by 111 patients and were significantly more common in the ritonavir-boosted lopinavir arm (72% versus 51%, P = 0.003). No seroconversions were observed during the study. CONCLUSIONS: PEP non-completion and adverse events were both significantly higher in patients allocated to ritonavir-boosted lopinavir. These data suggest that maraviroc is a well-tolerated antiretroviral that can be used in this setting. PMID- 26994093 TI - EFFECT OF RADIATION DOSE LEVEL ON ACCURACY AND PRECISION OF MANUAL SIZE MEASUREMENTS IN CHEST TOMOSYNTHESIS EVALUATED USING SIMULATED PULMONARY NODULES. AB - The aim of the present study was to investigate the dependency of the accuracy and precision of nodule diameter measurements on the radiation dose level in chest tomosynthesis. Artificial ellipsoid-shaped nodules with known dimensions were inserted in clinical chest tomosynthesis images. Noise was added to the images in order to simulate radiation dose levels corresponding to effective doses for a standard-sized patient of 0.06 and 0.04 mSv. These levels were compared with the original dose level, corresponding to an effective dose of 0.12 mSv for a standard-sized patient. Four thoracic radiologists measured the longest diameter of the nodules. The study was restricted to nodules located in high-dose areas of the tomosynthesis projection radiographs. A significant decrease of the measurement accuracy and intraobserver variability was seen for the lowest dose level for a subset of the observers. No significant effect of dose level on the interobserver variability was found. The number of non-measurable small nodules (<=5 mm) was higher for the two lowest dose levels compared with the original dose level. In conclusion, for pulmonary nodules at positions in the lung corresponding to locations in high-dose areas of the projection radiographs, using a radiation dose level resulting in an effective dose of 0.06 mSv to a standard-sized patient may be possible in chest tomosynthesis without affecting the accuracy and precision of nodule diameter measurements to any large extent. However, an increasing number of non-measurable small nodules (<=5 mm) with decreasing radiation dose may raise some concerns regarding an applied general dose reduction for chest tomosynthesis examinations in the clinical praxis. PMID- 26994094 TI - DOSE-RESPONSE STUDY USING MICRONUCLEUS CYTOME ASSAY: A TOOL FOR BIODOSIMETRY APPLICATION. AB - The present study is aimed at obtaining in vitro dose-response data for the induction of micronucleus (MN) and nucleoplasmic bridges (NPBs) in human lymphocytes using 60Co-gamma rays and 8 MeV pulsed electron beam. An attempt was made to validate the possibility of applying NPBs as new biodosimetry endpoint in the dose range of 0-6 Gy. A total of 1000 binucleated cells (BNCs) per dose point were evaluated for the frequency of MN and NPBs. From the study, it is clear that the dose-response increase of MN and NPBs is linear quadratic in nature. The study provides linear and quadratic parameter for biodosimetry application. The relative biological effectiveness value of the 8 MeV electron beam was estimated using slope values and is found to be 1.18 +/- 0.01 for MN/BNCs, 1.27 +/- 0.02 for the fraction of BNCs with MN, 1.16 +/- 0.13 for MN/(BNCs with MN) and 1.09+/ 0.01 for NPBs. PMID- 26994095 TI - RETROSPECTIVE DOSIMETRY USING SALTED SNACKS AND NUTS: A FEASIBILITY STUDY. AB - The possibility of using ordinary household table salt for dosimetry is suggested by its high sensitivity to ionising radiation, which generates a readout of optically stimulated luminescence (OSL). However, to exploit this finding for retrospective human dosimetry, it would be needed to find salt in close proximity to the exposed individual. Finding salty snacks frequently tucked into handbags, backpacks or pockets seemed to be a possibility; these items therefore became the test materials of the present study. The aluminium or cardboard packages used to exclude the moisture that makes crisps and nuts go soft and stale also helps to retain the induced OSL signal. Therefore, different snacks, either their salt component alone or mixed with the snack, are exposed to ionising radiation and then were assessed for their dosimetric properties. The results indicate the feasibility of using some salty snacks for dosimetry, with a minimum detectable dose as low as 0.2 mGy. PMID- 26994096 TI - BEAM QUALITY CORRECTION FACTORS FOR KAP METERS FOR LIGHTLY AND HEAVILY FILTERED X RAY BEAMS. AB - Kerma-area product (KAP) meters have a pronounced energy dependence when measuring air KAP for lightly filtered X-ray beams (RQR). Today, it is also common with more heavily filtered beams. In this work, the energy dependence for lightly as well as heavily filtered beams (RQC) was investigated for several KAP meter models. The relative energy dependence of the readings of an external and an internal KAP meter was determined relative to an ionisation chamber, which had been calibrated at the primary standards laboratory. As a complement to the measurements, the sensitivity of a KAP meter for various X-ray beam qualities was modelled using Monte Carlo simulations of photon transport and absorption. The result showed a variation in relative energy dependence of up to 30 % for KAP meters for RQC beam qualities compared with RQR qualities. A reduced sensitivity of KAP meters for heavily filtered beams in comparison with lightly filtered ones was found, and it is important that the beam-specific radiation quality correction factors are applied to correct the registered KAP values. PMID- 26994097 TI - EFFECT OF TIME EXPOSURE ON THERMOLUMINESCENCE GLOW CURVE FOR UV-INDUCED ZRO2:MG PHOSPHOR. AB - In this research, the effect of magnesium (Mg) impurity on thermoluminescence (TL) response of ZrO2 phosphors is studied experimentally. In the experimental procedure, ZrO2:Mg phosphors in the powder form were synthesised by the sol-gel method. The obtained hydrogel was dried in air and then calcinated in air at 1200 degrees C for 5 h and next was annealed at 250 degrees C for 2 h. Sample characterisations were done by X-ray diffraction and scanning electron microscopy. Obtained materials had monoclinic phase and porous microstructure. Then, known amounts of ZrO2:Mg powder were exposed to ultraviolet lamp from 0.5 to 120 min. The TL peaks were obtained at the same temperature as 75, 137 and 260 degrees C, respectively. Adding Mg to pure zirconia caused to increase TL intensity and shift peaks related to pure zirconia. The TL peaks of the pure zirconia were seen at the 83, 132 and 235 degrees C. Finally, ZrO2:Mg TL experimental results show the linear dose response, high stability and less fading. PMID- 26994099 TI - Optimizing Fluctuating Thermal Regime Storage of Developing Megachile rotundata (Hymenoptera: Megachilidae). AB - The alfalfa leafcutting bee, Megachile rotundata (F.), is the primary pollinator for alfalfa seed production in North America. Under current management practice, developing pupae are incubated at 29-30 degrees C until the adults emerge for pollination. If unfavorable spring weather delays peak alfalfa bloom, managers will cool pupae to slow development, which can increase mortality and causes sublethal effects. Previously, we demonstrated that exposure to a fluctuating thermal regime (FTR) increases survival and extends the viable storage period. To determine the optimal conditions for FTR during storage of developing M. rotundata, we examined four variables: temperature of the daily warm pulse, duration of the warm pulse, number of weeks exposed to the FTR treatment, and developmental stage of the bee. Survival was measured by successful eclosion to the adult stage. Under all conditions, exposure to FTR increased survival compared with exposure to a constant 6 degrees C. When the temperature of the daily warm pulse was 20-25 degrees C from a base temperature of 6 degrees C, and the pulse duration was extended to 3 h, survival rates were as high as those observed under standard storage conditions (29 degrees C). Under this FTR storage protocol, bee managers can delay emergence for ~8 wk without significant decreases in survival. Our findings have substantial economic implications for bee management and alfalfa seed production by increasing the flexibility and efficiency of M. rotundata adult emergence. PMID- 26994100 TI - The significance of developmental robustness for species diversity. AB - BACKGROUND: The origin of new species and of new forms is one of the fundamental characteristics of evolution. However, the mechanisms that govern the diversity and disparity of lineages remain poorly understood. Particularly unclear are the reasons why some taxa are vastly more species-rich than others and the manner in which species diversity and morphological disparity are interrelated. SCOPE AND CONCLUSIONS: Evolutionary innovations and ecological opportunities are usually cited as among the major factors promoting the evolution of species diversity. In many cases it is likely that these factors are positively reinforcing, with evolutionary innovations creating ecological opportunities that in turn foster the origin of new innovations. However, we propose that a third factor, developmental robustness, is very often essential for this reinforcement to be effective. Evolutionary innovations need to be stably and robustly integrated into the developmental genetic programme of an organism to be a suitable substrate for selection to 'explore' ecological opportunities and morphological 'design' space (morphospace). In particular, we propose that developmental robustness of the bauplan is often a prerequisite for the exploration of morphospace and to enable the evolution of further novelties built upon this bauplan Thus, while robustness may reduce the morphological disparity at one level, it may be the basis for increased morphological disparity and for evolutionary innovations at another level, thus fostering species diversity. PMID- 26994101 TI - Arabinogalactan proteins and pectin distribution during female gametogenesis in Quercus suber L. AB - BACKGROUND AND AIMS: Quercus suber L. (cork oak) is one of the most important monoecious tree species in semi-arid regions of Southern Europe, with a high ecological value and economic potential. However, as a result of its long reproductive cycle, complex reproductive biology and recalcitrant seeds, conventional breeding is demanding. In its complex reproductive biology, little is known about the most important changes that occur during female gametogenesis. Arabinogalactan proteins (AGPs) and pectins are the main components of plant cell walls and have been reported to perform common functions in cell differentiation and organogenesis of reproductive plant structures. AGPs have been shown to serve as important molecules in several steps of the reproductive process in plants, working as signalling molecules, associated with the sporophyte-gametophyte transition, and pectins have been implicated in pollen-pistil interactions before double fertilization. In this study, the distribution of AGP and pectin epitopes was assessed during female gametogenesis. METHODS: Immunofluorescence labelling of female flower cells was performed with a set of monoclonal antibodies (mAbs) directed to the carbohydrate moiety of AGPs (JIM8 and JIM13) and pectic homogalacturonans (HGs) (mAbs JIM5 and JIM7). KEY RESULTS: The selective labelling obtained with AGP and pectin mAbs JIM8, JIM13, JIM5 and JIM7 during Q. suber female gametogenesis shows that AGPs and pectic HG can work as markers for mapping gametophytic cell differentiation in this species. Pectic HG showed different distribution patterns, depending on their levels of methyl esterification. Methyl-esterified HGs showed a uniform distribution in the overall female flower cells before fertilization and a more specific pattern after fertilization. A low methyl-ester pectin distribution pattern during the different developmental stages appears to be related to the pathway that pollen tubes follow to reach the embryo sac. AGPs showed a more sparse distribution in early stages of development, but specific labelling is shown in the synergids and their filiform apparatus. CONCLUSIONS: The labelling obtained with anti-AGP and anti-pectin mAbs in Q. suber female flower cells showed a dynamic distribution of AGPs and pectic HGs, which may render these molecules useful molecular markers during female gametogenesis. Changes occurring during development will be determined in order to help describe cork oak ovule structural properties before and after fertilization, providing new insight to better understand Q. suber female gametogenesis. PMID- 26994098 TI - Cell migration in the developing rodent olfactory system. AB - The components of the nervous system are assembled in development by the process of cell migration. Although the principles of cell migration are conserved throughout the brain, different subsystems may predominantly utilize specific migratory mechanisms, or may display unusual features during migration. Examining these subsystems offers not only the potential for insights into the development of the system, but may also help in understanding disorders arising from aberrant cell migration. The olfactory system is an ancient sensory circuit that is essential for the survival and reproduction of a species. The organization of this circuit displays many evolutionarily conserved features in vertebrates, including molecular mechanisms and complex migratory pathways. In this review, we describe the elaborate migrations that populate each component of the olfactory system in rodents and compare them with those described in the well-studied neocortex. Understanding how the components of the olfactory system are assembled will not only shed light on the etiology of olfactory and sexual disorders, but will also offer insights into how conserved migratory mechanisms may have shaped the evolution of the brain. PMID- 26994102 TI - New integrative modules for multicolor-protein labeling and live-cell imaging in Saccharomyces cerevisiae. AB - Live-imaging analysis is performed in many laboratories all over the world. Various tools have been developed to enable protein labeling either in plasmid or genomic context in live yeast cells. Here, we introduce a set of nine integrative modules for the C-terminal gene tagging that combines three fluorescent proteins (FPs)-ymTagBFP, mCherry and yTagRFP-T with three dominant selection markers: geneticin, nourseothricin and hygromycin. In addition, the construction of two episomal modules for Saccharomyces cerevisiae with photostable yTagRFP-T is also referred to. Our cassettes with orange, red and blue FPs can be combined with other fluorescent probes like green fluorescent protein to prepare double- or triple-labeled strains for multicolor live-cell imaging. Primers for PCR amplification of the cassettes were designed in such a way as to be fully compatible with the existing PCR toolbox representing over 50 various integrative modules and also with deletion cassettes either for single or repeated usage to enable a cost-effective and an easy exchange of tags. New modules can also be used for biochemical analysis since antibodies are available for all three fluorescent probes. PMID- 26994103 TI - The endosomal sorting complex required for transport (ESCRT) is required for the sensitivity of yeast cells to nickel ions in Saccharomyces cerevisiae. AB - Nickel is one of the toxic environment metal pollutants and is linked to various human diseases. In this study, through a functional genomics approach we have identified 16 nickel-sensitive and 22 nickel-tolerant diploid deletion mutants of budding yeast genes, many of which are novel players in the regulation of nickel homeostasis. The 16 nickel-sensitive mutants are of genes mainly involved in the protein folding, modification and destination and the cellular transport processes, while the 22 nickel-tolerant mutants are of genes encoding components of ESCRT complexes as well as protein factors involved in both the cell wall integrity maintenance and the vacuolar protein sorting process. In consistence with their phenotypes, most of these nickel-sensitive mutants show reduced intracellular nickel contents, while the majority of these nickel-tolerant mutants show elevated intracellular nickel contents, as compared to the wild type in response to nickel stress. Our data provides a basis for our understanding the regulation of nickel homeostasis and molecular mechanisms of nickel-induced human pathogenesis. PMID- 26994104 TI - Editorial: The dark side of yeast biology. PMID- 26994105 TI - Life-threatening Petersen's hernia following open Beger's procedure. AB - Petersen's hernia (an internal hernia between the transverse mesocolon and Roux limb following Roux-en-Y reconstruction) is well described following laparoscopic gastric bypass surgery. We describe a Petersen-type hernia in a patient who had undergone complex open upper gastrointestinal surgery for chronic pancreatitis. PMID- 26994106 TI - A less invasive method for orthotopic injection of breast cancer cells into the mouse mammary gland. AB - Breast cancer is the most common type of cancer diagnosed in women, and the second most common cause of cancer-related deaths in women in North America. The use of laboratory mice in research is an essential tool for the study of breast cancer biology and for pre-clinical therapeutic development. While subcutaneous flank injections of cancer cells are widely used for studying breast cancer biology and for exploring novel therapies, orthotopic xenografting of tumors into the mouse mammary gland allow for the study of breast cancers in a biologically relevant microenvironment. In this study we report a modification of the method of orthotopic injections of cancer cells into the mouse mammary gland which greatly reduces the effects of surgery in mice including decreased wound size, procedure time and anesthesia. It also removes the risk of accidentally puncturing the peritoneal cavity. Consequently post-operative animal handling and stress are significantly reduced. All of these advantages are present without compromising procedure success rate. Therefore, this modification makes orthotopic mammary gland injection a more efficient procedure and greatly improves animal welfare. PMID- 26994107 TI - Methamphetamine Users Have Increased Dental Disease: A Propensity Score Analysis. AB - Methamphetamine (MA) users are assumed to have a high burden of tooth decay. Less clear is how the distribution and severity of dental caries in MA users differ from the general population. Using a covariate-balancing propensity score strategy, we investigated the differential effects of MA use on dental caries by comparing the patterns of decayed, missing, and filled teeth in a community sample of 571 MA users with a subset of 2,755 demographically similar control individuals selected from a National Health and Nutrition Examination Survey (NHANES) cohort. Recruited over a 2-y period with a stratified sampling protocol, the MA users underwent comprehensive dental examinations by 3 trained and calibrated dentists using NHANES protocols. Propensity scores were estimated with logistic regression based on background characteristics, and a subset of closely matched subjects was stratified into quintiles for comparisons. MA users were twice as likely to have untreated caries (odds ratio [OR] = 2.08; 95% confidence interval [95% CI]: 1.55 to 2.78) and 4 times more likely to have caries experience (OR = 4.06; 95% CI: 2.24 to 7.34) than the control group of NHANES participants. Additionally, MA users were twice as likely to have 2 more decayed, missing, or filled teeth (OR = 2.08; 95% CI: 1.29 to 2.79) than the NHANES participants. The differential involvement of the teeth surfaces in MA users was quite distinctive, with carious surface involvement being highest for the maxillary central incisors, followed by maxillary posterior premolars and molars. Users injecting MA had significantly higher rates of tooth decay compared with noninjectors (P = 0.04). Although MA users experienced decayed and missing dental surfaces more frequently than NHANES participants, NHANES participants had more restored surfaces, especially on molars. The high rates and distinctive patterns of dental caries observed could be used 1) to alert dentists to covert MA use in their patients and 2) as the basis for comprehensive management strategies. PMID- 26994108 TI - Integration-Free Reprogramming of Lamina Propria Progenitor Cells. AB - Producing induced pluripotent stem cells (iPSCs) from human tissue for use in personalized medicine strategies or therapeutic testing is at the forefront of medicine. Therefore, identifying a source of cells to reprogram that is easily accessible via a simple noninvasive procedure is of great clinical importance. Reprogramming these cells to iPSCs through nonintegrating methods for genetic manipulation is paramount for regenerative purposes. Here, we demonstrate reprogramming of oral mucosal lamina propria progenitor cells from patients undergoing routine dental treatment. Reprogramming was performed utilizing nonintegrating plasmids containing all 6 pluripotency genes (OCT4, SOX2, KLF4, NANOG, LIN28, and cMYC). Resulting iPSCs lacked genetic integration of the vector genes and had the ability to differentiate down mesoderm, ectoderm, and endoderm lineages, demonstrating pluripotency. In conclusion, oral mucosal lamina propria progenitor cells represent a source of cells that can be obtained with minimal invasion, as they can be taken concurrently with routine treatments. The resulting integration-free iPSCs therefore have great potential for use in personalized medicine strategies. PMID- 26994109 TI - Trends and complications of local anaesthesia in cataract surgery: an 8-year analysis of 12 992 patients. AB - BACKGROUND: Cataract surgery has progressed from large incision to smaller incisions, which do not require sutures. Anaesthesia too has progressed from general anaesthesia to local anaesthesia to topical anaesthesia. The ideal anaesthesia for cataract surgery would be one that is easy to administer, provides adequate pain relief during surgery and is associated with fewer complications. AIMS: This study was done to find out the most suitable anaesthesia for patients with fewer complications and also to look at the trend of anaesthesia being used. METHODS: A retrospective analysis was done of patients who underwent cataract surgery from 2007 to 2014 in Hospital Melaka. Data were obtained from the National Eye Database and analysed using SPSS. Trend of types of anaesthesia used and the associated complications with each were studied. RESULTS: The most frequently used anaesthesia was topical anaesthesia, which showed an upward trend followed by subtenon in turn showing a downward trend. Subtenon anaesthesia was associated with more intraoperative and postoperative complications while topical anaesthesia was associated with fewer complications. CONCLUSIONS: Topical anaesthesia has shown a steady increase in usage and is the ideal anaesthesia, which has been associated with fewer complications. PMID- 26994110 TI - Effects of switching from ranibizumab to aflibercept in eyes with exudative age related macular degeneration. AB - AIMS: To examine 12-month outcomes of eyes switching from intravitreal ranibizumab to aflibercept for neovascular age-related macular degeneration (nAMD). METHODS: Database observational study of eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that received ranibizumab for at least 12 months before switching to aflibercept and followed for at least 12 months after the switch. Visual acuity (VA) recorded at 12 months after the switch was analysed using locally weighted scatterplot smoothing curves. Lesion activity was graded according to a prospectively identified definition. Main outcomes were change in VA and treatment intervals 12 months after the treatment switch. Secondary outcomes included change in activity grading, effect of duration of treatment before switching and analysis of eyes that switched back. RESULTS: A total of 384 eyes switched from ranibizumab to aflibercept after a mean duration of 39.8 months on the original treatment. The mean VA did not change from the time of switching treatment (63.4, SD 15.9 logarithm of the minimum angle of resolution letters) to 12 months later (63.3, SD 16.7). While 10% of eyes gained 10 or more letters 12 months after the switch, 13% lost the same amount. The mean number of injections decreased by around one injection in the 12 months after switching (p<0.001), with a decrease in the proportion of choroidal neovascular membrane lesions that were graded as active. Eyes that had been treated for the longest time (49 or more months) before switching had worse vision at the point of switch but neither change in VA nor treatment interval was different between groups. The small proportion (6.9%) of eyes that switched back again to ranibizumab had already lost a mean of 5.2 letters from the first switch to the switch back and continued to lose vision at a similar rate for at least 6 months. CONCLUSIONS: The mean VA of eyes that switched treatments from ranibizumab to aflibercept was not different 12 months later. There was a modest increase in treatment intervals and a somewhat greater proportion of eyes that were graded as inactive after the switch. PMID- 26994111 TI - Developing transcutaneous nanoenabled anaesthetics for eyelid surgery. AB - PURPOSE: Local anaesthesia in eyelid surgery carries inherent risks, which has spurned ongoing investigation to identify needleless alternatives. Nanomedicines (particles ranging between 10 nm and 1000 nm in size) have shown promise in the transcutaneous delivery of certain drugs. In this study, we explore the feasibility of nanoenabled lidocaine delivery across an artificial skin analogue. MATERIALS AND METHODS: Three different lidocaine-loaded nanocarriers were characterised. Diffusion studies were performed through cellulose membranes using customised Franz cells. The nanocarriers included polymeric micelles (PMs) (Soluplus), solid lipid nanoparticles (SLNs) (Tripalmitin: Lecithin: Labrasol: polysorbate-20: water; 3.33:1:40:1:4.67 w/w) and self-nanoemulsifying drug delivery systems (SNEDDS) (Capryol-90: Transcutol: Labrasol; 1:3:6 w/w). Particles were characterised in terms of size, zeta-potential and morphology. One way analysis of variance (ANOVA) with post hoc Tukey's tests were used to assess differences in permeation at a significance of p<0.05. RESULTS: Lidocaine loading was highest in SNEDDs (50+/-2.1 mg/g) compared with PMs (13.4+/-0.6 mg/mL) and SLNs (2.8+/-0.5 mg/mL). All particles possessed a size below 150 nm, illustrated good colloidal stability with a negative zeta-potential and a spherical morphology as demonstrated by transmission electron microscopy images. Cumulative lidocaine concentration after 6 h was significant for both PMs (345.7+/-23.8 ug/cm(2)/h) and SNEDDS (224.8+/-118.2 ug/cm(2)/h) compared with SLNs (127.3+/ 25.4 ug/cm(2)/h). However, SLNs provided controlled release of lidocaine with a linear gradient that continued to increase up to 6 h. DISCUSSION: These results highlight the potential capability of nanoparticle lidocaine delivery in eyelid surgery. The achieved flux for all nanomedicines was higher than that reported for currently approved topical lidocaine formulations (including EMLA cream). PMID- 26994112 TI - Association of iris surface features with iris parameters assessed by swept source optical coherence tomography in Asian eyes. AB - BACKGROUND/AIMS: To characterise the association of iris surface features (crypts, furrows and colour) with iris volume and curvature assessed by swept source optical coherence tomography (SSOCT) in Asian eyes. METHODS: Iris crypts (by number and size) and furrows (by number and circumferential extent) were graded from iris photographs. Iris colour was measured by a customised algorithm written on MATLAB (MathWorks, Natick, Massachusetts, USA). The iris was imaged by SSOCT (SS-1000, CASIA, Tomey, Nagoya, Japan). The associations of surface features with iris parameters were analysed using a generalised estimating equation. RESULTS: A total of 1704 subjects (3297 eyes) were included in the analysis. The majority was Chinese (86.4%), and 63.2% were females, and their mean age (+/-SD) was 61.4+/-6.6 years. After adjusting for age, sex, ethnicity, pupil size and corneal arcus, higher iris crypt grade was independently associated with smaller iris volume (beta=-0.54, p<0.001), whereas darker irides and higher iris furrow grade were associated with larger iris volume (beta= 0.041, p<0.001) and (beta=0.233, p<0.001), respectively. Lighter coloured irides with more crypts and/or more furrows were also associated with less convexity (crypts: beta=-0.003, p=0.03; furrows: beta=-0.004, p=0.007; and colour: beta= 0.001, p=0.005). CONCLUSIONS: Iris surface features were highly correlated with iris volume and curvature. Irides with more crypts have a smaller volume; and darker irides with more furrows have a larger volume. Lighter irides with more crypts and/or furrows have less convexity. PMID- 26994113 TI - GC-MS Analysis and Volatile Profile Comparison for the Characteristic Smell from Liang-wai Gan Cao (Glycyrrhiza uralensis) and Honey-Roasting Products. AB - The characteristic smell of Liang-wai Gan Cao (Glycyrrhiza uralensis) and honey roasting products was comprehensively analyzed using gas chromatography-mass spectrometry (GC-MS). Steam distillation and headspace solid-phase microextraction (HS-SPME) were used to extract volatile organic compounds (VOCs). Multiple fibers of SPME may reflect the samples' comprehensive information to the greatest extent, depending on their chemical characters. After chemometric resolution and spectra interpretation, many aroma compounds could be identified from GC-MS data. As a result, principal component analysis was set for the differentiation of several G. uralensis samples in different regions, and some important peaks could be found. Next, VOCs' profiles of honey-roasting products suggested that the flavors could be influenced by honey and pharmaceutical technologies. PMID- 26994114 TI - The impact of a model-based clinical regional registry for attention-deficit hyperactivity disorder. AB - This article describes the development and clinical impact of the Italian Regional ADHD Registry, aimed at collecting and monitoring diagnostic and therapeutic pathways of care for attention-deficit hyperactivity disorder children and adolescents, launched by the Italian Lombardy Region in June 2011. In particular, the model-based software used to run the registry and manage clinical care data acquisition and monitoring, is described. This software was developed using the PROSAFE programme, which is already used for data collection in many Italian intensive care units, as a stand-alone interface case report form. The use of the attention-deficit hyperactivity disorder regional registry led to an increase in the appropriateness of the clinical management of all patients included in the registry, proving to be an important instrument in ensuring an appropriate healthcare strategy for children and adolescents with attention-deficit/hyperactivity disorder. PMID- 26994115 TI - Disturbances of the Basic Self and Prodromal Symptoms Among Young Adolescents From the Community: A Pilot Population-Based Study. AB - BACKGROUND AND GOAL: Recent findings have provided preliminary support for the notion that basic self-disturbances (SD) are related to prodromal symptoms among nonpsychotic help-seeking adolescents. As a sizable proportion of adolescents who are at risk do not seek help, this study attempts to assess the extent to which these findings can be generalized to the entire population of adolescents who are at risk for psychosis. METHOD: The concurrent relationship between SD and prodromal symptoms was explored in a sample of 100 non-help-seeking adolescents (age 13-15) from the community. SD were assessed with the Examination of Anomalous Self-Experience (EASE); prodromal symptoms and syndromes were assessed with the Structured Interview for Prodromal Syndromes (SIPS); psychosocial functioning was assessed with the "Social and Role Global Functioning Scales"; and level of distress with the Mood and Anxiety States Questionnaire (MASQ). RESULTS: SD significantly correlated with sub-clinical psychotic symptoms (r = .70, P < .0001). This correlation was significantly stronger than those of SD with mood symptoms and social functioning. Finally, SD was the single best concurrent predictor of prodromal symptoms and syndromes. CONCLUSIONS: These results provide preliminary support for the generalizability of the association between SD and prodromal symptoms for the entire population of adolescents who are clinically at high risk for psychosis. In addition, they further support the notion that this association is both specific and unique. PMID- 26994116 TI - Cushing Syndrome Cardiomyopathy: Clinicopathologic Impact of Cortisol Normalization. PMID- 26994117 TI - Development of a biomechanical model of the wrist joint for patient-specific model guided surgical therapy planning: Part 1. AB - An enhanced musculoskeletal biomechanical model of the wrist joint is presented in this article. The developed computational model features the two forearm bones radius and ulna, the eight wrist bones, the five metacarpal bones, and a soft tissue apparatus. Validation of the model was based on information taken from the literature as well as own experimental passive in vitro motion analysis of eight cadaver specimens. The computational model is based on the multi-body simulation software AnyBody. A comprehensive ligamentous apparatus was implemented allowing the investigation of ligament function. The model can easily patient specific personalized on the basis of image information. The model enables simulation of individual wrist motion and predicts trends correctly in the case of changing kinematics. Therefore, patient-specific multi-body simulation models are potentially valuable tools for surgeons in pre- and intraoperative planning of implant placement and orientation. PMID- 26994118 TI - A biomechanical model of the wrist joint for patient-specific model guided surgical therapy: Part 2. AB - An enhanced musculoskeletal biomechanical model of the wrist joint is presented in this article. The computational model is based on the multi-body simulation software AnyBody. Multi body dynamic musculoskeletal models capable of predicting muscle forces and joint contact pressures simultaneously would be valuable for studying clinical issues related to wrist joint degeneration and restoration. In this study, the simulation model of the wrist joint was used for investigating deeper the biomechanical function of the wrist joint. In representative physiological scenarios, the joint behavior and muscle forces were computed. Furthermore, the load transmission of the proximal wrist joint was investigated. The model was able to calculate the parameters of interest that are not easily obtainable experimentally, such as muscle forces and proximal wrist joint forces. In the case of muscle force investigation, the computational model was able to accurately predict the computational outcome for flexion and extension motion. In the case of force distribution of the proximal wrist joint, the model was able to predict accurately the computational outcome for an axial load of 140 N. The presented model and approach of using a multi-body simulation model are anticipated to have value as a predictive clinical tool including effect of injuries or anatomical variations and initial outcome of surgical procedures for patient-specific planning and custom implant design. Therefore, patient-specific multi-body simulation models are potentially valuable tools for surgeons in pre- and intraoperative planning of implant placement and orientation. PMID- 26994119 TI - Prediction of knee joint moment changes during walking in response to wedged insole interventions. AB - Wedged insoles are prescribed for medial knee osteoarthritis to reduce the knee adduction moment; however, it is currently not possible to predict which patients will in fact experience reduced moments. The purpose of this study was to identify a simple method using two-dimensional data for predicting the expected change in knee adduction moments with wedged insoles. Knee adduction moments during walking were determined for healthy individuals (n = 15) and individuals with medial knee osteoarthritis (n = 19) while wearing their own shoe without an insole (control), with a 6-mm medial wedge and with a 6-mm lateral wedge. The percent changes relative to control were determined. Then, participants completed single-step trials with each footwear condition where only the changes in mediolateral positions of the knee joint center, shank center of mass, ankle joint center, and foot center of mass relative to control were determined. These variables were used as predictors in regression equations where the change in knee adduction moment during walking was the dependent variable. The change in mediolateral positions of the lower extremity during a single step significantly predicted the change in knee adduction moment during walking for the lateral wedge in both the healthy (R(2) = 0.72, p = 0.008) and knee osteoarthritis (R(2) = 0.52, p = 0.026) groups, and also for the medial wedge in both the healthy (R(2) = 0.67, p = 0.016) and knee osteoarthritis (R(2) = 0.54, p = 0.020) groups. The method of using mediolateral position data from a single-step movement to predict walking biomechanics was successful. These data are relatively simple to collect and analyze, offering the possibility for future incorporation into a wedge prediction system. PMID- 26994120 TI - Palliative care nursing education features more prominently in 2015 than 2005: Results from a nationwide survey and qualitative analysis of curricula. AB - BACKGROUND: Making palliative care accessible to all citizens who are in need of this type of care requires effective policies and education. Moreover, healthcare professionals have an ethical and legal responsibility to ensure quality palliative care. Nevertheless, palliative care has had traditionally a limited emphasis in healthcare professionals' undergraduate education. AIM: To study the current status of palliative care education in nursing undergraduate curricula and compare 2005 and 2015 findings. DESIGN: An online survey was sent to all state schools providing nursing undergraduate education in Portugal (N = 21). The survey assessed if and how palliative care was included in the curricula, and whether or not national and international recommendations for palliative care nursing education were followed. Further analysis included the content of available curricula/syllabi. SETTING/PARTICIPANTS: A total of 19 schools completed the survey (90% of response rate). These institutions are geographically dispersed and representative of state nursing educational institutions in Portugal. RESULTS: In 2015, all participant schools integrated palliative care in their curricula; nine schools had palliative care as an independent curricular unit (an 800% increase compared to 2005). While in 2005, only 14 out of 23 (61%) schools included palliative care explicitly in their curricula; in 2015, all 19 participant schools did so. National and international recommendations were followed. CONCLUSION: The inclusion of palliative care within nursing undergraduate curricula strongly increased from 2005 to 2015. Further research is needed to understand the contribution of education in the access, care provision, quality and development of palliative care in this country. PMID- 26994121 TI - Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study. AB - BACKGROUND: Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis. METHODS AND RESULTS: After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61). CONCLUSIONS: In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938. PMID- 26994122 TI - Transcatheter Valve-in-Valve Implantation for Failing Bioprosthetic Triscupid Valves: Completing the Quest. PMID- 26994124 TI - Expected thrombectomy caseload. PMID- 26994125 TI - High-intensity interval training: key data needed to bridge the gap from laboratory to public health policy. PMID- 26994123 TI - Transcatheter Tricuspid Valve-in-Valve Implantation for the Treatment of Dysfunctional Surgical Bioprosthetic Valves: An International, Multicenter Registry Study. AB - BACKGROUND: Off-label use of transcatheter aortic and pulmonary valve prostheses for tricuspid valve-in-valve implantation (TVIV) within dysfunctional surgical tricuspid valve (TV) bioprostheses has been described in small reports. METHODS AND RESULTS: An international, multicenter registry was developed to collect data on TVIV cases. Patient-related factors, procedural details and outcomes, and follow-up data were analyzed. Valve-in-ring or heterotopic TV implantation procedures were not included. Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. The median age was 40 years, and 71% of patients were in New York Heart Association class III or IV. Among 152 patients in whom TVIV was attempted with a Melody (n=94) or Sapien (n=58) valve, implantation was successful in 150, with few serious complications. After TVIV, both the TV inflow gradient and tricuspid regurgitation grade improved significantly. During follow-up (median, 13.3 months), 22 patients died, 5 within 30 days; all 22 patients were in New York Heart Association class III or IV, and 9 were hospitalized before TVIV. There were 10 TV reinterventions, and 3 other patients had significant recurrent TV dysfunction. At follow-up, 77% of patients were in New York Heart Association class I or II (P<0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type. CONCLUSIONS: TVIV with commercially available transcatheter prostheses is technically and clinically successful in patients of various ages across a wide range of valve size. Although preimplantation clinical status was associated with outcome, many patients in New York Heart Association class III or IV at baseline improved. TVIV should be considered a viable option for treatment of failing TV bioprostheses. PMID- 26994126 TI - Enthusiasm for prescriptive clinical prediction rules (eg, back pain and more): a quick word of caution. PMID- 26994127 TI - Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study. AB - BACKGROUND: Carotid atherosclerosis is associated with subclinical ischemic cerebrovascular disease, but its role in hemorrhage-prone small vessel disease represented by cerebral microbleed (CMB)-is unclear, although vascular risk factors underlie both conditions. We hypothesized that persons with carotid atherosclerosis would have higher risk of CMB, particularly in deep regions. METHODS AND RESULTS: We studied 1243 participants in the Framingham Offspring Study (aged 56.9+/-8.8 years; 53% women) with carotid ultrasound available on 2 occasions (1995-1998 and 2005-2008) prior to brain magnetic resonance imaging. Using multivariable logistic regression, we related baseline carotid stenosis, baseline intima-media thickness, and site-specific carotid intima-media thickness progression (at internal and common carotid locations) to the prevalence and location (lobar or deep plus mixed) of CMB. In addition, we assessed effect modification by lipid levels and use of statin and antithrombotic medications. Carotid stenosis >=25% (a marker of cerebrovascular atherosclerosis) was associated with presence of CMB overall (Odds Ratio 2.20, 95% CI 1.10-4.40) and at deep and mixed locations (odds ratio 3.60, 95% CI 1.23-10.5). Baseline carotid intima-media thickness was not associated with CMB. Progression of common carotid artery intima-media thickness among persons on hypertension treatment was associated with lower risk of deep and mixed CMB (odds ratio per SD 0.41, 95% CI 0.18-0.96). CONCLUSIONS: Cumulative vascular risk factor exposure may increase the risk of CMB, especially in deep regions. The apparent paradoxical association of carotid intima-media thickness progression with lower risk of CMB may reflect benefits of intensive vascular risk factor treatment among persons with higher cardiovascular risk and deserves further investigation. If replicated, the results may have potential implications for assessment of preventive and therapeutic interventions for subclinical cerebral hemorrhage. PMID- 26994128 TI - Cardiopulmonary Dysfunction and Adiponectin in Adolescents With Type 2 Diabetes. AB - BACKGROUND: Myocardial mechanics are altered in adults with obesity and type 2 diabetes (T2D); insulin resistance and adipokines have been implicated as important risk factors for cardiovascular disease, but these relationships are poorly described in adolescents. We hypothesized that obese adolescents and adolescents with T2D would have abnormal cardiac function compared to lean adolescents. In addition, we hypothesized that insulin sensitivity (IS), adiposity, and adipokines would be associated with altered cardiac strain and cardiopulmonary fitness in adolescents with T2D. METHODS AND RESULTS: Adolescents (15+/-2 years) with T2D (n=37), obesity without diabetes (n=41), and lean controls (n=31) of similar age and pubertal stage underwent echocardiography with speckle tracking, assessment of IS by hyperinsulinemic-euglycemic clamp, body composition by dual-energy x-ray absorptiometry, peak oxygen consumption (VO2peak) by cycle ergometry, adiponectin, and leptin. Compared to lean and to obese controls, adolescents with T2D had significantly lower cardiac circumferential strain (CS) (-18.9+/-4.6 [T2D] versus -21.5+/-3.5 [obese] versus 22.0+/-4.2% [lean], P=0.04) and VO2peak (37.6+/-7.5 [T2D] versus 43.4+/-8.2 [obese] versus 47.6+/-8.6 mL/lean kg/min [lean], P<0.0001). In T2D youth, VO2peak was associated with CS, and the association remained significant after adjusting for age, sex, and IS (beta+/-SE: -0.73+/-0.26, P=0.02). Among adolescents with T2D, CS was also associated with adiponectin, longitudinal strain with leptin, and VO2peak with adiponectin and IS. CONCLUSIONS: Adolescents with T2D had abnormal CS and reduced VO2peak compared to obese and lean controls, which may represent the earliest evidence of cardiac functional impairment in T2D. Low adiponectin, rather than conventional risk factors and IS, correlated with CS, while both adiponectin and IS related to cardiopulmonary fitness. PMID- 26994129 TI - Relationship Between the Duration of Cardiopulmonary Resuscitation and Favorable Neurological Outcomes After Out-of-Hospital Cardiac Arrest: A Prospective, Nationwide, Population-Based Cohort Study. AB - BACKGROUND: The determination of appropriate duration of in-the-field cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) patients is one of the biggest challenges for emergency medical service providers and clinicians. The appropriate CPR duration before termination of resuscitation remains unclear and may differ based on initial rhythm. We aimed to determine the relationship between CPR duration and post-OHCA outcomes. METHODS AND RESULTS: We analyzed the records of 17 238 OHCA patients (age >=18 years) who achieved prehospital return of spontaneous circulation. Data were prospectively recorded in a nationwide, Japanese database between 2011 and 2012. The time from CPR initiation to prehospital return of spontaneous circulation (CPR duration) was calculated. The primary end point was 1-month survival with favorable neurological outcomes (Cerebral Performance Category [CPC] scale; CPC 1-2). The 1 month CPC 1-2 rate was 21.8% (n=3771). CPR duration was inversely associated with 1-month CPC 1-2 (adjusted unit odds ratio: 0.95, 95% CI: 0.94-0.95). Among all patients, a cumulative proportion of >99% of 1-month CPC 1-2 was achieved with a CPR duration of 35 minutes. When sorted by the initial rhythm, the CPR duration producing more than 99% of survivors with CPC 1-2 was 35 minutes for shockable rhythms and pulseless electrical activity, and 42 minutes for asystole. CONCLUSIONS: CPR duration was independently and inversely associated with favorable 1-month neurological outcomes. The critical prehospital CPR duration for OHCA was 35 minutes in patients with initial shockable rhythms and pulseless electrical activity, and 42 minutes in those with initial asystole. PMID- 26994130 TI - Eliciting Patient Risk Willingness in Clinical Consultations as a Means of Improving Decision-Making of Aortic Valve Replacement. AB - BACKGROUND: Treatment decisions for aortic valve replacement (AVR) should be sensitive to patient preferences. However, we lack knowledge of patient preferences and how to obtain them. METHODS AND RESULTS: We assessed the mortality risk patients were willing to accept when undergoing AVR by using the Standard Gamble method and aimed to show how this risk willingness was affected by level of disease burden. We report findings from 439 patients, aged >18 years with severe aortic stenosis who were referred for evaluation of AVR to our institution. The vast majority of patients accepted a mortality risk regarded as high or prohibitive according to current guidelines. Of the 439 patients, 51% patients were willing to forego surgery with high mortality risk (8-50%) and 19% were willing accept a prohibitive mortality risk (>50%) as defined in current guidelines. However, the risk willingness varied considerably. Acceptance of prohibitive risk willingness (>50%) was associated with reporting of 3 to 5 different restricting symptoms, with an odds ratio of 4.07 (95% CI 1.56-10.59) opposed by increasing score on EuroQol-Visual Analog Scale, with an odds ratio of 0.99 (95% CI 0.97-1.00). The poor ability to predict risk willingness based on available clinical variables and health status suggests that other factors may be important advocating the need for tools for soliciting patient's preferences individually. CONCLUSION: When undergoing AVR, patients were willing to accept considerably higher perioperative risk than what is considered acceptable in current guidelines and practice. Patient preferences varied considerably, and they should be directly assessed and taken into account in decision-making and guidelines. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/. Unique identifier: NCT01794832. PMID- 26994131 TI - Incidence and Prognostic Significance of Depressive Symptoms in Peripheral Artery Disease. AB - BACKGROUND: We compared the incidence of depression, defined by a Geriatric Depression Score (GDS) >=6, between people with versus without peripheral artery disease (PAD). We determined whether depressive symptoms were associated with increased mortality in people with and without PAD. METHODS AND RESULTS: Nine hundred and fifty-one PAD patients and 478 non-PAD patients were recruited from Chicago medical centers and followed prospectively. At baseline and annually, participants completed the GDS (0-15 scale, score >=6=depression) and 6-minute walk. Cause of death was confirmed with death certificates. The prevalence of a GDS >=6 at baseline was 186/951 (19.6%) among PAD versus 63/478 (13.2%) among non PAD participants (P=0.003). During a mean follow-up of 2.7+/-1.2 years, 122/712 (17.1%) of participants with PAD versus 51/403 (12.7%) without PAD developed a GDS >=6 (P=0.047). Adjusting for age, sex, race, comorbidities, and other confounders, PAD participants had an increased rate of developing a GDS >=6 compared to non-PAD participants (hazard ratio=1.54 (95% CI=1.05-2.25, P=0.026). This association was not statistically significant after adjusting for 6-minute walk (P=0.258). Among PAD participants, a baseline GDS >=6 was associated with increased all-cause mortality, adjusting for confounders (hazard ratio=1.57, 95% CI=1.12-2.21, P=0.009). This association was not significant after adjusting for 6-minute walk (P=0.224). CONCLUSIONS: People with PAD have a higher incidence of depressive symptoms than people without PAD. In PAD, depressive symptoms are associated with increased all-cause and cardiovascular mortality. These associations are explained in part by poorer 6-minute walk among people with PAD and among depressed people with PAD, respectively. PMID- 26994132 TI - Off-Hour Admission and Mortality Risk for 28 Specific Diseases: A Systematic Review and Meta-Analysis of 251 Cohorts. AB - BACKGROUND: A considerable amount of studies have examined the relationship between off-hours (weekends and nights) admission and mortality risk for various diseases, but the results remain equivocal. METHODS AND RESULTS: Through a search of EMBASE, PUBMED, Web of Science, and Cochrane Database of Systematic Reviews, we identified cohort studies that evaluated the association between off-hour admission and mortality risk for disease. In a random effects meta-analysis of 140 identified articles (251 cohorts), off-hour admission was strongly associated with increased mortality for aortic aneurysm (odds ratio, 1.52; 95% CI, 1.30 1.77), breast cancer (1.50, 1.21-1.86), leukemia (1.45, 1.17-1.79), respiratory neoplasm (1.32, 1.20-1.26), pancreatic cancer (1.32, 1.12-1.56), malignant neoplasm of genitourinary organs (1.27, 1.08-1.49), colorectal cancer (1.26, 1.07 1.49), pulmonary embolism (1.20, 1.13-1.28), arrhythmia and cardiac arrest (1.19, 1.09-1.29), and lymphoma (1.19, 1.06-1.34). Weaker (odds ratio <1.19) but statistically significant association was noted for renal failure, traumatic brain injury, heart failure, intracerebral hemorrhage, subarachnoid hemorrhage, stroke, gastrointestinal bleeding, myocardial infarction, chronic obstructive pulmonary disease, and bloodstream infections. No association was found for hip fracture, pneumonia, intestinal obstruction, aspiration pneumonia, peptic ulcer, trauma, diverticulitis, and neonatal mortality. Overall, off-hour admission was associated with increased mortality for 28 diseases combined (odds ratio, 1.11; 95% CI, 1.10-1.13). CONCLUSIONS: Off-hour admission is associated with increased mortality risk, and the associations varied substantially for different diseases. Specialists, nurses, as well as hospital administrators and health policymakers can take these findings into consideration to improve the quality and continuity of medical services. PMID- 26994133 TI - Comparison of Long-Term Clinical Outcomes of Lesions Exhibiting Focal and Segmental Peri-Stent Contrast Staining. AB - BACKGROUND: Peri-stent contrast staining (PSS) after metallic drug-eluting stent deployment is associated with target lesion revascularization and very late stent thrombosis. However, the type of PSS that influences the clinical outcomes is unknown. Therefore, we aimed to reveal which PSS type was influencing clinical outcomes. METHODS AND RESULTS: This study included 5580 de novo lesions of 4405 patients who were implanted with a first- or second-generation drug-eluting stent and who were evaluated using follow-up angiography within 12 months after stent implantation. We compared the clinical outcomes of patients divided into focal PSS and segmental PSS groups for 6 years after stent implantation. Total PSS was observed in 97 lesions (2.2%), of which 42 and 55 lesions were focal and segmental PSS, respectively. Baseline characteristics were similar between groups, except for intraoperative chronic total occlusion (segmental PSS=47.3% versus focal PSS=11.9%, P=0.0001). The incidence of segmental PSS tended to be higher in patients with a first-generation drug-eluting stent (83.6% versus 16.4%, P=0.05). The cumulative incidence of stent thrombosis in the 6 years of segmental PSS group was significantly higher than that of the focal PSS group (13.9% versus 0%, P=0.04). The cumulative incidence of overall target lesion revascularization for restenosis, excluding target lesion revascularization procedures for stent thrombosis, was significantly higher in the segmental PSS group (38.0% versus 0%, P=0.01). CONCLUSIONS: The incidence of segmental PSS tended to be higher in patients with a first-generation drug-eluting stent and appeared to be significantly associated with target lesion revascularization and stent thrombosis. PMID- 26994134 TI - Horticultural Production Systems Influence Ground Beetle (Coleoptera: Carabidae) Distribution and Diversity in Cucurbits. AB - Commercial cucurbit production typically involves agriculturally intensive practices, with fields prepared using conventional tillage, plasticulture, and chemically based pest management. Conservation-based management options are limited. In this study, we consider two alternative strategies, strip tillage and the use of row covers. We compare their impact on the beneficial carabid beetle (Coleoptera: Carabidae) community in melons and squash, following conventional or organic systems, over two years. Multivariate analysis demonstrated that soil management system (strip tillage versus plasticulture) was the primary variable influencing carabid distribution; row cover was a less important factor. The response to soil management was species dependent. Some dominant species, such as Harpalus pensylvanicus DeGeer, demonstrated no preference for a particular soil treatment. For others, including the tiger beetle, Cicindela punctulata Olivier, and a slug predator, Chlaenius tricolor Dejean, activity-density was higher in strip-tillage production systems. Our analysis suggested that strip-tillage production systems support a richer, more diverse carabid community. These results demonstrate that even within intensive annual horticultural systems, production practices can play a critical role in shaping the beneficial arthropod community, potentially encouraging or limiting ecosystem services. PMID- 26994135 TI - Brief Heat Stress Negatively Affects the Population Fitness and Host Feeding of Aphelinus asychis (Hymenoptera: Aphelinidae) Parasitizing Myzus persicae (Hemiptera: Aphididae). AB - Aphelinus asychis Walker (Hymenoptera: Aphelinidae), a polyphagous parasitoid, has been widely used as a biological control agent against Myzus persicae (Sulzer) (Hemiptera: Aphididae) and other aphid species. In order to ensure the successful biological control of M. persicae, we evaluated the influence of brief heat stresses (32.5, 35.0, 37.5, 40.0, and 41.5 degrees C for 1 h), which occur frequently during the summer or under greenhouse conditions, on survival, longevity, host feeding, and parasitism of A. asychis that were reared on chili pepper at 25 degrees C in the laboratory. Our results showed several major consequences on the parasitoid adults after brief heat stress. First, the survival of briefly heat stress-treated A. asychis female and male adults decreased significantly at >=37.5 degrees C and their longevity decreased as well. Second, the number of M. persicae nymphs infesting chili pepper killed through host feeding by the treated A. asychis females decreased significantly. Third, the cumulative number of mummified aphids and female progeny produced by the treated A. asychis also decreased significantly at >=37.5 degrees C. Our results indicated that a brief heat stress on A. asychis adults caused severe effects on major life history traits and total numbers of hosts killed by host feeding and parasitism, suggesting that high temperatures should be avoided to ensure the success of biological control of M. persicae and other aphid species using this parasitoid species. PMID- 26994136 TI - Kindlin-3 Is Essential for the Resting alpha4beta1 Integrin-mediated Firm Cell Adhesion under Shear Flow Conditions. AB - Integrin-mediated rolling and firm cell adhesion are two critical steps in leukocyte trafficking. Integrin alpha4beta1 mediates a mixture of rolling and firm cell adhesion on vascular cell adhesion molecule-1 (VCAM-1) when in its resting state but only supports firm cell adhesion upon activation. The transition from rolling to firm cell adhesion is controlled by integrin activation. Kindlin-3 has been shown to bind to integrin beta tails and trigger integrin activation via inside-out signaling. However, the role of kindlin-3 in regulating resting alpha4beta1-mediated cell adhesion is not well characterized. Herein we demonstrate that kindlin-3 was required for the resting alpha4beta1 mediated firm cell adhesion but not rolling adhesion. Knockdown of kindlin-3 significantly decreased the binding of kindlin-3 to beta1 and down-regulated the binding affinity of the resting alpha4beta1 to soluble VCAM-1. Notably, it converted the resting alpha4beta1-mediated firm cell adhesion to rolling adhesion on VCAM-1 substrates, increased cell rolling velocity, and impaired the stability of cell adhesion. By contrast, firm cell adhesion mediated by Mn(2+)-activated alpha4beta1 was barely affected by knockdown of kindlin-3. Structurally, lack of kindlin-3 led to a more bent conformation of the resting alpha4beta1. Thus, kindlin-3 plays an important role in maintaining a proper conformation of the resting alpha4beta1 to mediate both rolling and firm cell adhesion. Defective kindlin-3 binding to the resting alpha4beta1 leads to a transition from firm to rolling cell adhesion on VCAM-1, implying its potential role in regulating the transition between integrin-mediated rolling and firm cell adhesion. PMID- 26994137 TI - Characterization of Diabetogenic CD8+ T Cells: IMMUNE THERAPY WITH METABOLIC BLOCKADE. AB - Type 1 diabetes mellitus is caused by the killing of insulin-producing beta cells by CD8+T cells. The disease progression, which is chronic, does not follow a course like responses to conventional antigens such as viruses, but accelerates as glucose tolerance deteriorates. To identify the unique features of the autoimmune effectors that may explain this behavior, we analyzed diabetogenic CD8+ T cells that recognize a peptide from the diabetes antigen IGRP (NRP-V7 reactive) in prediabetic NOD mice and compared them to others that shared their phenotype (CD44(+)CD62L(lo)PD-1(+)CXCR3(+)) but negative for diabetes antigen tetramers and to LCMV (lymphocytic choriomeningitis)-reactive CD8+ T cells. There was an increase in the frequency of the NRP-V7-reactive cells coinciding with the time of glucose intolerance. The T cells persisted in hyperglycemic NOD mice maintained with an insulin pellet despite destruction of beta cells. We compared gene expression in the three groups of cells compared with the other two subsets of cells, and the NRP-V7-reactive cells exhibited gene expression of memory precursor effector cells. They had reduced cellular proliferation and were less dependent on oxidative phosphorylation. When prediabetic NOD mice were treated with 2-deoxyglucose to block aerobic glycolysis, there was a reduction in the diabetes antigen versus other cells of similar phenotype and loss of lymphoid cells infiltrating the islets. In addition, treatment of NOD mice with 2 deoxyglucose resulted in improved beta cell granularity. These findings identify a link between metabolic disturbances and autoreactive T cells that promotes development of autoimmune diabetes. PMID- 26994139 TI - Allosteric Modulation of the Calcium-sensing Receptor Rectifies Signaling Abnormalities Associated with G-protein alpha-11 Mutations Causing Hypercalcemic and Hypocalcemic Disorders. AB - Germline loss- and gain-of-function mutations of G-protein alpha-11 (Galpha11), which couples the calcium-sensing receptor (CaSR) to intracellular calcium (Ca(2+) i) signaling, lead to familial hypocalciuric hypercalcemia type 2 (FHH2) and autosomal dominant hypocalcemia type 2 (ADH2), respectively, whereas somatic Galpha11 mutations mediate uveal melanoma development by constitutively up regulating MAPK signaling. Cinacalcet and NPS-2143 are allosteric CaSR activators and inactivators, respectively, that ameliorate signaling disturbances associated with CaSR mutations, but their potential to modulate abnormalities of the downstream Galpha11 protein is unknown. This study investigated whether cinacalcet and NPS-2143 may rectify Ca(2+) i alterations associated with FHH2- and ADH2-causing Galpha11 mutations, and evaluated the influence of germline gain of-function Galpha11 mutations on MAPK signaling by measuring ERK phosphorylation, and assessed the effect of NPS-2143 on a uveal melanoma Galpha11 mutant. WT and mutant Galpha11 proteins causing FHH2, ADH2 or uveal melanoma were transfected in CaSR-expressing HEK293 cells, and Ca(2+) i and ERK phosphorylation responses measured by flow-cytometry and Alphascreen immunoassay following exposure to extracellular Ca(2+) (Ca(2+) o) and allosteric modulators. Cinacalcet and NPS-2143 rectified the Ca(2+) i responses of FHH2- and ADH2-associated Galpha11 loss- and gain-of-function mutations, respectively. ADH2-causing Galpha11 mutations were demonstrated not to be constitutively activating and induced ERK phosphorylation following Ca(2+) o stimulation only. The increased ERK phosphorylation associated with ADH2 and uveal melanoma mutants was rectified by NPS-2143. These findings demonstrate that CaSR-targeted compounds can rectify signaling disturbances caused by germline and somatic Galpha11 mutations, which respectively lead to calcium disorders and tumorigenesis; and that ADH2-causing Galpha11 mutations induce non-constitutive alterations in MAPK signaling. PMID- 26994138 TI - Structural Studies of Medicago truncatula Histidinol Phosphate Phosphatase from Inositol Monophosphatase Superfamily Reveal Details of Penultimate Step of Histidine Biosynthesis in Plants. AB - The penultimate enzyme in the histidine biosynthetic pathway catalyzes dephosphorylation of l-histidinol 1-phosphate (HOLP) into l-histidinol. The recently discovered in Arabidopsis thaliana plant-type histidinol phosphate phosphatase (HPP) shares no homology with the two other HPP superfamilies known previously in prokaryotes and resembles myo-inositol monophosphatases (IMPases). In this work, identification of an HPP enzyme from a model legume, Medicago truncatula (MtHPP) was based on the highest sequence identity to A. thaliana enzyme. Biochemical assays confirmed that MtHPP was able to cleave inorganic phosphate from HOLP but not from d-myo-inositol-1-phosphate, the main substrate of IMPases. Dimers of MtHPP, determined by size exclusion chromatography, in the presence of CO2 or formaldehyde form mutual, methylene-bridged cross-links between Lys(158) and Cys(245) residues. Four high resolution crystal structures, namely complexes with HOLP (substrate), l-histidinol (product), and PO4 (3-) (by product) as well as the structure showing the cross-linking between two MtHPP molecules, provide detailed structural information on the enzyme. Based on the crystal structures, the enzymatic reaction mechanism of IMPases is accustomed to fit the data for MtHPP. The enzymatic reaction, which requires Mg(2+) cations, is catalyzed mainly by amino acid residues from the N-terminal domain. The C terminal domain, sharing little identity with IMPases, is responsible for the substrate specificity (i.e. allows the enzyme to distinguish between HOLP and d myo-inositol-1-phosphate). Structural features, mainly the presence of a conserved Asp(246), allow MtHPP to bind HOLP specifically. PMID- 26994140 TI - The Stress-responsive Gene ATF3 Mediates Dichotomous UV Responses by Regulating the Tip60 and p53 Proteins. AB - The response to UV irradiation is important for a cell to maintain its genetic integrity when challenged by environmental genotoxins. An immediate early response to UV irradiation is the rapid induction of activating transcription factor 3 (ATF3) expression. Although emerging evidence has linked ATF3 to stress pathways regulated by the tumor suppressor p53 and the histone acetyltransferase Tip60, the role of ATF3 in the UV response remains largely unclear. Here, we report that ATF3 mediated dichotomous UV responses. Although UV irradiation enhanced the binding of ATF3 to Tip60, knockdown of ATF3 expression decreased Tip60 stability, thereby impairing Tip60 induction by UV irradiation. In line with the role of Tip60 in mediating UV-induced apoptosis, ATF3 promoted the death of p53-defective cells in response to UV irradiation. However, ATF3 could also activate p53 and promote p53-mediated DNA repair, mainly through altering histone modifications that could facilitate recruitment of DNA repair proteins (such as DDB2) to damaged DNA sites. As a result, ATF3 rather protected the p53 wild-type cells from UV-induced apoptosis. Our results thus indicate that ATF3 regulates cell fates upon UV irradiation in a p53-dependent manner. PMID- 26994142 TI - Regulation of Beclin 1 Protein Phosphorylation and Autophagy by Protein Phosphatase 2A (PP2A) and Death-associated Protein Kinase 3 (DAPK3). AB - Autophagy is an evolutionarily conserved intracellular degradation system that is involved in cell survival and activated in various diseases, including cancer. Beclin 1 is a central scaffold protein that assembles components for promoting or inhibiting autophagy. Association of Beclin 1 with its interacting proteins is regulated by the phosphorylation of Beclin 1 by various Ser/Thr kinases, but the Ser/Thr phosphatases that regulate these phosphorylation events remain unknown. Here we identify Ser-90 in Beclin 1 as a regulatory site whose phosphorylation is markedly enhanced in cells treated with okadaic acid, an inhibitor of protein phosphatase 2A (PP2A). Beclin 1 Ser-90 phosphorylation is induced in skeletal muscle tissues isolated from starved mice. The Beclin 1 S90A mutant blocked starvation-induced autophagy. We found association of PP2A B55alpha with Beclin 1, which dissociate by starvation. We also found that death-associated protein kinase 3 directly phosphorylates Beclin 1 Ser-90. We propose that physiological regulation of Beclin 1 Ser-90 phosphorylation by PP2A and death-associated protein kinase 3 controls autophagy. PMID- 26994141 TI - Identification of Amino Acid Residues in Fibroblast Growth Factor 14 (FGF14) Required for Structure-Function Interactions with Voltage-gated Sodium Channel Nav1.6. AB - The voltage-gated Na(+) (Nav) channel provides the basis for electrical excitability in the brain. This channel is regulated by a number of accessory proteins including fibroblast growth factor 14 (FGF14), a member of the intracellular FGF family. In addition to forming homodimers, FGF14 binds directly to the Nav1.6 channel C-tail, regulating channel gating and expression, properties that are required for intrinsic excitability in neurons. Seeking amino acid residues with unique roles at the protein-protein interaction interface (PPI) of FGF14.Nav1.6, we engineered model-guided mutations of FGF14 and validated their impact on the FGF14.Nav1.6 complex and the FGF14:FGF14 dimer formation using a luciferase assay. Divergence was found in the beta-9 sheet of FGF14 where an alanine (Ala) mutation of Val-160 impaired binding to Nav1.6 but had no effect on FGF14:FGF14 dimer formation. Additional analysis revealed also a key role of residues Lys-74/Ile-76 at the N-terminal of FGF14 in the FGF14.Nav1.6 complex and FGF14:FGF14 dimer formation. Using whole-cell patch clamp electrophysiology, we demonstrated that either the FGF14(V160A) or the FGF14(K74A/I76A) mutation was sufficient to abolish the FGF14-dependent regulation of peak transient Na(+) currents and the voltage-dependent activation and steady-state inactivation of Nav1.6; but only V160A with a concomitant alanine mutation at Tyr-158 could impede FGF14-dependent modulation of the channel fast inactivation. Intrinsic fluorescence spectroscopy of purified proteins confirmed a stronger binding reduction of FGF14(V160A) to the Nav1.6 C tail compared with FGF14(K74A/I76A) Altogether these studies indicate that the beta-9 sheet and the N terminus of FGF14 are well positioned targets for drug development of PPI-based allosteric modulators of Nav channels. PMID- 26994143 TI - The Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Subunit of the Capsid-recruited Pre-messenger RNA Cleavage Factor I (CFIm) Complex Mediates HIV 1 Integration into Genes. AB - HIV-1 favors integration into active genes and gene-enriched regions of host cell chromosomes, thus maximizing the probability of provirus expression immediately after integration. This requires cleavage and polyadenylation specificity factor 6 (CPSF6), a cellular protein involved in pre-mRNA 3' end processing that binds HIV-1 capsid and connects HIV-1 preintegration complexes to intranuclear trafficking pathways that link integration to transcriptionally active chromatin. CPSF6 together with CPSF5 and CPSF7 are known subunits of the cleavage factor I (CFIm) 3' end processing complex; however, CPSF6 could participate in additional protein complexes. The molecular mechanisms underpinning the role of CPSF6 in HIV 1 infection remain to be defined. Here, we show that a majority of cellular CPSF6 is incorporated into the CFIm complex. HIV-1 capsid recruits CFIm in a CPSF6 dependent manner, which suggests that the CFIm complex mediates the known effects of CPSF6 in HIV-1 infection. To dissect the roles of CPSF6 and other CFIm complex subunits in HIV-1 infection, we analyzed virologic and integration site targeting properties of a CPSF6 variant with mutations that prevent its incorporation into CFIm We show, somewhat surprisingly, that CPSF6 incorporation into CFIm is not required for its ability to direct preferential HIV-1 integration into genes. The CPSF5 and CPSF7 subunits appear to have only a minor, if any, role in this process even though they appear to facilitate CPSF6 binding to capsid. Thus, CPSF6 alone controls the key molecular interactions that specify HIV-1 preintegration complex trafficking to active chromatin. PMID- 26994144 TI - Immunotherapy with a HER2-Targeting Listeria Induces HER2-Specific Immunity and Demonstrates Potential Therapeutic Effects in a Phase I Trial in Canine Osteosarcoma. AB - PURPOSE: Recombinant Listeria vaccines induce tumor-specific T-cell responses that eliminate established tumors and prevent metastatic disease in murine cancer models. We used dogs with HER2/neu(+) appendicular osteosarcoma, a well recognized spontaneous model for pediatric osteosarcoma, to determine whether a highly attenuated, recombinant Listeria monocytogenes expressing a chimeric human HER2/neu fusion protein (ADXS31-164) could safely induce HER2/neu-specific immunity and prevent metastatic disease. EXPERIMENTAL DESIGN: Eighteen dogs that underwent limb amputation or salvage surgery and adjuvant chemotherapy were enrolled in a phase I dose escalation clinical trial and received either 2 * 10(8), 5 * 10(8), 1 * 10(9), or 3.3 * 10(9) CFU of ADXS31-164 intravenously every 3 weeks for 3 administrations. RESULTS: Only low-grade, transient toxicities were observed. ADXS31-164 broke peripheral tolerance and induced antigen-specific IFNgamma responses against the intracellular domain of HER2/neu in 15 of 18 dogs within 6 months of treatment. Furthermore, ADXS31-164 reduced the incidence of metastatic disease and significantly increased duration of survival time and 1-, 2-, and 3-year survival rates when compared with a historical control group with HER2/neu(+) appendicular osteosarcoma treated with amputation and chemotherapy alone. CONCLUSIONS: These findings demonstrate that ADXS31-164 administered in the setting of minimal residual disease can induce HER2/neu-specific immunity and may reduce the incidence of metastatic disease and prolong overall survival in a clinically relevant, spontaneous, large animal model of cancer. These findings, therefore, have important translational relevance for children with osteosarcoma and adults with other HER2/neu(+) cancers. Clin Cancer Res; 22(17); 4380-90. (c)2016 AACR. PMID- 26994146 TI - Immune and Stromal Classification of Colorectal Cancer Is Associated with Molecular Subtypes and Relevant for Precision Immunotherapy. AB - PURPOSE: The tumor microenvironment is formed by many distinct and interacting cell populations, and its composition may predict patients' prognosis and response to therapies. Colorectal cancer is a heterogeneous disease in which immune classifications and four consensus molecular subgroups (CMS) have been described. Our aim was to integrate the composition of the tumor microenvironment with the consensus molecular classification of colorectal cancer. EXPERIMENTAL DESIGN: We retrospectively analyzed the composition and the functional orientation of the immune, fibroblastic, and angiogenic microenvironment of 1,388 colorectal cancer tumors from three independent cohorts using transcriptomics. We validated our findings using immunohistochemistry. RESULTS: We report that colorectal cancer molecular subgroups and microenvironmental signatures are highly correlated. Out of the four molecular subgroups, two highly express immune specific genes. The good-prognosis microsatellite instable-enriched subgroup (CMS1) is characterized by overexpression of genes specific to cytotoxic lymphocytes. In contrast, the poor-prognosis mesenchymal subgroup (CMS4) expresses markers of lymphocytes and of cells of monocytic origin. The mesenchymal subgroup also displays an angiogenic, inflammatory, and immunosuppressive signature, a coordinated pattern that we also found in breast (n = 254), ovarian (n = 97), lung (n = 80), and kidney (n = 143) cancers. Pathologic examination revealed that the mesenchymal subtype is characterized by a high density of fibroblasts that likely produce the chemokines and cytokines that favor tumor-associated inflammation and support angiogenesis, resulting in a poor prognosis. In contrast, the canonical (CMS2) and metabolic (CMS3) subtypes with intermediate prognosis exhibit low immune and inflammatory signatures. CONCLUSIONS: The distinct immune orientations of the colorectal cancer molecular subtypes pave the way for tailored immunotherapies. Clin Cancer Res; 22(16); 4057 66. (c)2016 AACR. PMID- 26994145 TI - MultiDimensional ClinOmics for Precision Therapy of Children and Adolescent Young Adults with Relapsed and Refractory Cancer: A Report from the Center for Cancer Research. AB - PURPOSE: We undertook a multidimensional clinical genomics study of children and adolescent young adults with relapsed and refractory cancers to determine the feasibility of genome-guided precision therapy. EXPERIMENTAL DESIGN: Patients with non-central nervous system solid tumors underwent a combination of whole exome sequencing (WES), whole transcriptome sequencing (WTS), and high-density single-nucleotide polymorphism array analysis of the tumor, with WES of matched germline DNA. Clinically actionable alterations were identified as a reportable germline mutation, a diagnosis change, or a somatic event (including a single nucleotide variant, an indel, an amplification, a deletion, or a fusion gene), which could be targeted with drugs in existing clinical trials or with FDA approved drugs. RESULTS: Fifty-nine patients in 20 diagnostic categories were enrolled from 2010 to 2014. Ages ranged from 7 months to 25 years old. Seventy three percent of the patients had prior chemotherapy, and the tumors from these patients with relapsed or refractory cancers had a higher mutational burden than that reported in the literature. Thirty patients (51% of total) had clinically actionable mutations, of which 24 (41%) had a mutation that was currently targetable in a clinical trial setting, 4 patients (7%) had a change in diagnosis, and 7 patients (12%) had a reportable germline mutation. CONCLUSIONS: We found a remarkably high number of clinically actionable mutations in 51% of the patients, and 12% with significant germline mutations. We demonstrated the clinical feasibility of next-generation sequencing in a diverse population of relapsed and refractory pediatric solid tumors. Clin Cancer Res; 22(15); 3810-20. (c)2016 AACR. PMID- 26994147 TI - Is watch and wait still acceptable for patients with low-grade follicular lymphoma? AB - Follicular lymphoma (FL) represents more than 20% of all non-Hodgkin lymphomas worldwide and approximately 30% of the non-Hodgkin lymphomas diagnosed in the United States. Although occasionally localized at the time of diagnosis, most patients have disseminated disease. However, patients are frequently asymptomatic, and this, in combination with a long median survival, led to the initial studies of observing asymptomatic patients without initial therapy, ie, "watch and wait." Since the initial report of watch and wait as a treatment strategy for patients with low-grade FL, our understanding of the biology of the disease has advanced; multiple active new agents have been introduced into practice, and the survival of patients with low-grade FL has improved. Given these changes, is watch and wait still an acceptable treatment recommendation for a newly diagnosed patient with low-grade FL? PMID- 26994148 TI - Ibrutinib responsive central nervous system involvement in chronic lymphocytic leukemia. PMID- 26994150 TI - Paracetamol does not reduce pain or improve function in osteoarthritis, study shows. PMID- 26994149 TI - Preclinical models of acute and chronic graft-versus-host disease: how predictive are they for a successful clinical translation? AB - Despite major advances in recent years, graft-versus-host disease (GVHD) remains a major life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). To improve our therapeutic armory against GVHD, preclinical evidence is most frequently generated in mouse and large animal models of GVHD. However, because every model has shortcomings, it is important to understand how predictive the different models are and why certain findings in these models could not be translated into the clinic. Weaknesses of the animal GVHD models include the irradiation only-based conditioning regimen, the homogenous donor/recipient genetics in mice, canine or non-human primates (NHP), anatomic site of T cells used for transfer in mice, the homogenous microbial environment in mice housed under specific pathogen-free conditions, and the lack of pharmacologic GVHD prevention in control groups. Despite these major differences toward clinical allo-HCT, findings generated in animal models of GVHD have led to the current gold standards for GVHD prophylaxis and therapy. The homogenous nature of the preclinical models allows for reproducibility, which is key for the characterization of the role of a new cytokine, chemokine, transcription factor, microRNA, kinase, or immune cell population in the context of GVHD. Therefore, when carefully balancing reasons to apply small and large animal models, it becomes evident that they are valuable tools to generate preclinical hypotheses, which then have to be rigorously evaluated in the clinical setting. In this study, we discuss several clinical approaches that were motivated by preclinical evidence, novel NHP models and their advantages, and highlight the recent advances in understanding the pathophysiology of GVHD. PMID- 26994151 TI - MicroRNAs: small molecule, big potential for coronary artery disease. PMID- 26994152 TI - Revascularization in stable coronary artery disease: a combined perspective from an interventional cardiologist and a cardiac surgeon. AB - It is now half a century since the start of coronary bypass graft surgery (CABG) with the first percutaneous coronary intervention (PCI) following just over a decade later. The relative merits of PCI vs. CABG for stable coronary artery disease (stable-CAD) have continued to be debated ever since and have been the focus of around 20 randomized trials and numerous registry studies, systematic reviews, and meta-analyses. The aim of this review is to identify areas of agreement, disagreement, and uncertainties in the role of PCI and CABG in patients with stable-CAD. PMID- 26994153 TI - Aortic valve calcification: a bone of contention. PMID- 26994154 TI - Does targeting ibutilide-resistant CFAE improve outcomes for catheter ablation of persistent AF? PMID- 26994155 TI - Mixed aortic valve disease: midterm outcome and predictors of adverse events. AB - AIMS: The aim of this article is to determine freedom from adverse events (AE) defined as symptoms, aortic valve replacement (AVR), or death in the mixed aortic valve disease (MAVD) population. METHODS AND RESULTS: We reviewed patients with moderate/severe MAVD followed at Mayo Clinic from 1994-2013. Only asymptomatic patients with normal ejection fraction and trileaflet aortic valve were included. Cox proportional-hazard models and Kaplan-Meier method were used. We identified 213 patients with moderate/severe MAVD; mean age was 69 years (+/-11) and 67% were males. An AE endpoint was reached in 172 patients, and 69% of these AEs occurred in moderate MAVD (peak velocity of 3-3.9 m/s). Mean follow-up was 10.1 +/- 3 years, and mean time to AE was 2.9 +/- 2.1 years. A mechanical prosthesis was implanted in 71/151 (47%), and 54/151 (36%) had concomitant coronary artery bypass grafting and/or aorta replacement during AVR. Early surgical mortality was 0.7%. Freedom from AE endpoint was 42% [confidence interval (CI) 39-45%] and 30% (CI 27-33%) at 3 and 5 years, respectively. Predictors of AE were peak aortic velocity [hazard ratio (HR) 2.73; CI 1.97-2.84, P < 0.0001] for every 1 m/s difference and having severe stenosis or severe regurgitation at presentation (HR 2.58; CI 2.01-4.44, P = 0.001). CONCLUSION: Moderate MAVD had high rate of AEs comparable to severe isolated aortic stenosis and should be followed as such. Patients with severe MAVD should be evaluated at least every 6 months because half of them will become symptomatic and require AVR within 1 year. PMID- 26994157 TI - Correction for Parr et al., Glycogen Synthase Kinase 3 Inhibition Promotes Lysosomal Biogenesis and Autophagic Degradation of the Amyloid-beta Precursor Protein. PMID- 26994160 TI - Cinematic Vertigo--and Enjoyable Once You Relax Into It. PMID- 26994161 TI - You See Me. PMID- 26994168 TI - Continuous quality improvement programme in cardiovascular surgery: the Latin American perspective. PMID- 26994169 TI - Use of an Edwards Sapien S3 valve to replace a dysfunctional mechanical mitral valve in an 11-year old boy: another small step for surgical and interventional collaboration. AB - An 11-year old boy, with complex left ventricular morphology in the setting of repaired double outlet right ventricle developed progressive mitral regurgitation leading to a repair which failed, necessitating replacement of the valve with a 21 mm St. Jude mechanical prosthesis. He represented 3 weeks later in extremis with signs of severe mitral stenosis. The valve was replaced via a hybrid technique with a 26 mm Edwards Sapien 3 valve mounted on a MEMO 3D annuloplasty ring. One year later, the valve is functioning well with no regurgitation or evidence of an inflow gradient. PMID- 26994170 TI - Determination of the wingsnap sonation mechanism of the golden-collared manakin (Manacus vitellinus). AB - Male golden-collared manakins (Manacus vitellinus), small suboscine passeriform birds of Panamanian forests, communicate acoustically using a variety of non vocal sonations. The most prominent sonations are single or multiple intense 'wingsnaps' with a dominant acoustic frequency around 5 kHz. Several hypotheses have been proposed addressing the source of the sound, ranging from purely aerodynamic origins (due to a rapid jet of air formed by the wings or by a 'whiplike' motion) to purely structural origins (such as physical contact of the wings), but without definitive assessment. Using anatomical analysis as well as high-speed video and synchronized audio recordings, we show that compared with related species, M. vitellinus radii are morphologically unique and confirm that they collide over the back of the bird at the moment (+/-1 ms) the wingsnap is produced. Using aeroacoustic theory, we quantitatively estimate the acoustic signatures from several sonation mechanisms. We conclude that only the physical contact hypothesis, wherein the wing collisions create the sound, is consistent with the measured sonation. PMID- 26994171 TI - Center of mass velocity-based predictions in balance recovery following pelvis perturbations during human walking. AB - In many simple walking models, foot placement dictates the center of pressure location and ground reaction force components, whereas humans can modulate these aspects after foot contact. Because of the differences, it is unclear to what extent predictions made by models are valid for human walking. Yet, both model simulations and human experimental data have previously indicated that the center of mass (COM) velocity plays an important role in regulating stable walking. Here, perturbed human walking was studied to determine the relationship of the horizontal COM velocity at heel strike and toe-off with the foot placement location relative to the COM, the forthcoming center of pressure location relative to the COM, and the ground reaction forces. Ten healthy subjects received mediolateral and anteroposterior pelvis perturbations of various magnitudes at toe-off, during 0.63 and 1.25 m s(-1) treadmill walking. At heel strike after the perturbation, recovery from mediolateral perturbations involved mediolateral foot placement adjustments proportional to the mediolateral COM velocity. In contrast, for anteroposterior perturbations, no significant anteroposterior foot placement adjustment occurred at this heel strike. However, in both directions the COM velocity at heel strike related linearly to the center of pressure location at the subsequent toe-off. This relationship was affected by the walking speed and was, for the slow speed, in line with a COM velocity-based control strategy previously applied by others in a linear inverted pendulum model. Finally, changes in gait phase durations suggest that the timing of actions could play an important role during the perturbation recovery. PMID- 26994172 TI - Head roll stabilisation in the nocturnal bull ant Myrmecia pyriformis: implications for visual navigation. AB - Ant foragers are known to memorise visual scenes that allow them to repeatedly travel along idiosyncratic routes and to return to specific places. Guidance is provided by a comparison between visual memories and current views, which critically depends on how well the attitude of the visual system is controlled. Here we show that nocturnal bull ants stabilise their head to varying degrees against locomotion-induced body roll movements, and this ability decreases as light levels fall. There are always un-compensated head roll oscillations that match the frequency of the stride cycle. Head roll stabilisation involves both visual and non-visual cues as ants compensate for body roll in complete darkness and also respond with head roll movements when confronted with visual pattern oscillations. We show that imperfect head roll control degrades navigation relevant visual information and discuss ways in which navigating ants may deal with this problem. PMID- 26994173 TI - Phenophysiological variation of a bee that regulates hive humidity, but not hive temperature. AB - Seasonal acclimatisation of thermal tolerance, evaporative water loss and metabolic rate, along with regulation of the hive environment, are key ways whereby hive-based social insects mediate climatic challenges throughout the year, but the relative importance of these traits remains poorly understood. Here, we examined seasonal variation in metabolic rate and evaporative water loss of worker bees, and seasonal variation of hive temperature and relative humidity (RH), for the stingless bee Austroplebeia essingtoni (Apidae: Meliponini) in arid tropical Australia. Both water loss and metabolic rate were lower in the cooler, dry winter than in the hot, wet summer at most ambient temperatures between 20 degrees C and 45 degrees C. Contrary to expectation, thermal tolerance thresholds were higher in the winter than in the summer. Hives were cooler in the cooler, dry winter than in the hot, wet summer, linked to an apparent lack of hive thermoregulation. The RH of hives was regulated at approximately 65% in both seasons, which is higher than unoccupied control hives in the dry season, but less than unoccupied control hives in the wet season. Although adaptations to promote water balance appear more important for survival of A. essingtoni than traits related to temperature regulation, their capacity for water conservation is coincident with increased thermal tolerance. For these small, eusocial stingless bees in the arid tropics, where air temperatures are relatively high and stable compared with temperate areas, regulation of hive humidity appears to be of more importance than temperature for maintaining hive health. PMID- 26994174 TI - Phenotypic plasticity in three Daphnia genotypes in response to predator kairomone: evidence for an involvement of chitin deacetylases. AB - The genetic background of inducible morphological defences in Daphnia is still largely unknown. Dissolved infochemicals from the aquatic larvae of the phantom midge Chaoborus induce so-called 'neck-teeth' in the first three post-embryonic stages of Daphnia pulex This defence has become a textbook example of inducible defences. In a target gene approach, by using three Daphnia genotypes which show a gradient of neck-teeth induction in response to equal amounts of kairomone, we report a high correlation of neck-teeth induction in Daphnia pulex and relative gene expression of two chitin deacetylases. Further, previous studies suggested genes from both the juvenoid and the insulin hormone signalling pathways as well as several morphogenetic genes downstream to be responsible for neck-teeth induction in D. pulex However, these data were not supported by our study. None of the three D. pulex clones showed an upregulation of these previously proposed candidate genes as a response to predator kairomone, which is interpreted as the result of refined methods used for both RNA sampling and kairomone enrichment yielding unambiguous results compared with earlier studies. The assessment of a clonal gradient of Daphnia in the presence and absence of infochemicals provides a promising approach to identify further genes involved in the induction of morphological defences by correlating gene expression and morphology. PMID- 26994175 TI - Intra-specific variation in wing morphology and its impact on take-off performance in blue tits (Cyanistes caeruleus) during escape flights. AB - Diurnal and seasonal increases in body mass and seasonal reductions in wing area may compromise a bird's ability to escape, as less of the power available from the flight muscles can be used to accelerate and elevate the animal's centre of mass. Here, we investigated the effects of intra-specific variation in wing morphology on escape take-off performance in blue tits (Cyanistes caeruleus). Flights were recorded using synchronised high-speed video cameras and take-off performance was quantified as the sum of the rates of change of the kinetic and potential energies of the centre of mass. Individuals with a lower wing loading, WL (WL=body weight/wing area) had higher escape take-off performance, consistent with the increase in lift production expected from relatively larger wings. Unexpectedly, it was found that the total power available from the flight muscles (estimated using an aerodynamic analysis) was inversely related to WL. This could simply be because birds with a higher WL have relatively smaller flight muscles. Alternatively or additionally, variation in the aerodynamic load on the wing resulting from differences in wing morphology will affect the mechanical performance of the flight muscles via effects on the muscle's length trajectory. Consistent with this hypothesis is the observation that wing beat frequency and relative downstroke duration increase with decreasing WL; both are factors that are expected to increase muscle power output. Understanding how wing morphology influences take-off performance gives insight into the potential risks associated with feather loss and seasonal and diurnal fluctuations in body mass. PMID- 26994176 TI - Recovery of locomotion after injury in Drosophila melanogaster depends on proprioception. AB - Locomotion is necessary for survival in most animal species. However, injuries to the appendages mediating locomotion are common. We assess the recovery of walking in Drosophila melanogaster following leg amputation. Whereas flies pre-amputation explore open arenas in a symmetric fashion on average, foreleg amputation induces a strong turning bias away from the side of the amputation. However, we find that unbiased walking behavior returns over time in wild-type flies, while recovery is significantly impaired in proprioceptive mutants. To identify the biomechanical basis of this locomotor impairment and recovery, we then examine individual leg motion (gait) at a fine scale. A minimal mathematical model that links neurodynamics to body mechanics during walking shows that redistributing leg forces between the right and left side enables the observed recovery. Altogether, our study suggests that proprioceptive input from the intact limbs plays a crucial role in the behavioral plasticity associated with locomotor recovery after injury. PMID- 26994177 TI - Using accelerometers to remotely and automatically characterize behavior in small animals. AB - Activity budgets in wild animals are challenging to measure via direct observation because data collection is time consuming and observer effects are potentially confounding. Although tri-axial accelerometers are increasingly employed for this purpose, their application in small-bodied animals has been limited by weight restrictions. Additionally, accelerometers engender novel complications, as a system is needed to reliably map acceleration to behaviors. In this study, we describe newly developed, tiny acceleration-logging devices (1.5-2.5 g) and use them to characterize behavior in two chipmunk species. We collected paired accelerometer readings and behavioral observations from captive individuals. We then employed techniques from machine learning to develop an automatic system for coding accelerometer readings into behavioral categories. Finally, we deployed and recovered accelerometers from free-living, wild chipmunks. This is the first time to our knowledge that accelerometers have been used to generate behavioral data for small-bodied (<100 g), free-living mammals. PMID- 26994178 TI - Wake analysis of aerodynamic components for the glide envelope of a jackdaw (Corvus monedula). AB - Gliding flight is a relatively inexpensive mode of flight used by many larger bird species, where potential energy is used to cover the cost of aerodynamic drag. Birds have great flexibility in their flight configuration, allowing them to control their flight speed and glide angle. However, relatively little is known about how this flexibility affects aerodynamic drag. We measured the wake of a jackdaw (Corvus monedula) gliding in a wind tunnel, and computed the components of aerodynamic drag from the wake. We found that induced drag was mainly affected by wingspan, but also that the use of the tail has a negative influence on span efficiency. Contrary to previous work, we found no support for the separated primaries being used in controlling the induced drag. Profile drag was of similar magnitude to that reported in other studies, and our results suggest that profile drag is affected by variation in wing shape. For a folded tail, the body drag coefficient had a value of 0.2, rising to above 0.4 with the tail fully spread, which we conclude is due to tail profile drag. PMID- 26994179 TI - Automated detection of feeding strikes by larval fish using continuous high-speed digital video: a novel method to extract quantitative data from fast, sparse kinematic events. AB - Using videography to extract quantitative data on animal movement and kinematics constitutes a major tool in biomechanics and behavioral ecology. Advanced recording technologies now enable acquisition of long video sequences encompassing sparse and unpredictable events. Although such events may be ecologically important, analysis of sparse data can be extremely time-consuming and potentially biased; data quality is often strongly dependent on the training level of the observer and subject to contamination by observer-dependent biases. These constraints often limit our ability to study animal performance and fitness. Using long videos of foraging fish larvae, we provide a framework for the automated detection of prey acquisition strikes, a behavior that is infrequent yet critical for larval survival. We compared the performance of four video descriptors and their combinations against manually identified feeding events. For our data, the best single descriptor provided a classification accuracy of 77-95% and detection accuracy of 88-98%, depending on fish species and size. Using a combination of descriptors improved the accuracy of classification by ~2%, but did not improve detection accuracy. Our results indicate that the effort required by an expert to manually label videos can be greatly reduced to examining only the potential feeding detections in order to filter false detections. Thus, using automated descriptors reduces the amount of manual work needed to identify events of interest from weeks to hours, enabling the assembly of an unbiased large dataset of ecologically relevant behaviors. PMID- 26994180 TI - Modeling observed animal performance using the Weibull distribution. AB - To understand how organisms adapt, researchers must link performance and microhabitat. However, measuring performance, especially maximum performance, can sometimes be difficult. Here, we describe an improvement over previous techniques that only consider the largest observed values as maxima. Instead, we model expected performance observations via the Weibull distribution, a statistical approach that reduces the impact of rare observations. After calculating group level weighted averages and variances by treating individuals separately to reduce pseudoreplication, our approach resulted in high statistical power despite small sample sizes. We fitted lizard adhesive performance and bite force data to the Weibull distribution and found that it closely estimated maximum performance in both cases, illustrating the generality of our approach. Using the Weibull distribution to estimate observed performance greatly improves upon previous techniques by facilitating power analyses and error estimations around robustly estimated maximum values. PMID- 26994181 TI - Beyond body size: muscle biochemistry and body shape explain ontogenetic variation of anti-predatory behaviour in the lizard Salvator merianae. AB - Anti-predatory behaviour evolves under the strong action of natural selection because the success of individuals avoiding predation essentially defines their fitness. Choice of anti-predatory strategies is defined by prey characteristics as well as environmental temperature. An additional dimension often relegated in this multilevel equation is the ontogenetic component. In the tegu Salvator merianae, adults run away from predators at high temperatures but prefer fighting when it is cold, whereas juveniles exhibit the same flight strategy within a wide thermal range. Here, we integrate physiology and morphology to understand ontogenetic variation in the temperature-dependent shift of anti-predatory behaviour in these lizards. We compiled data for body shape and size, and quantified enzyme activity in hindlimb and head muscles, testing the hypothesis that morphophysiological models explain ontogenetic variation in behavioural associations. Our prediction is that juveniles exhibit body shape and muscle biochemistry that enhance flight strategies. We identified biochemical differences between muscles mainly in the LDH:CS ratio, whereby hindlimb muscles were more glycolytic than the jaw musculature. Juveniles, which often use evasive strategies to avoid predation, have more glycolytic hindlimb muscles and are much smaller when compared with adults 1-2 years old. Ontogenetic differences in body shape were identified but marginally contributed to behavioural variation between juvenile and adult tegus, and variation in anti-predatory behaviour in these lizards resides mainly in associations between body size and muscle biochemistry. Our results are discussed in the ecological context of predator avoidance by individuals differing in body size living at temperature-variable environments, where restrictions imposed by the cold could be compensated by specific phenotypes. PMID- 26994182 TI - Biological activity of the enantiomers of 3-methylhentriacontane, a queen pheromone of the ant Lasius niger. AB - Queen pheromones are essential for regulation of the reproductive division of labor in eusocial insect species. Although only the queen is able to lay fertilized eggs and produce females, in some cases workers may develop their ovaries and lay male-destined eggs, thus reducing the overall colony efficiency. As long as the queen is healthy, it is usually in the workers' collective interest to work for the colony and remain sterile. Queens signal their fertility via pheromones, which may have a primer effect, affecting the physiology of workers, or a releaser effect, influencing worker behavior. The queen pheromone of the ant Lasius niger was among the first queen pheromones of social insects to be identified. Its major component is 3-methylhentriacontane (3-MeC31), which is present in relatively large amounts on the queen's cuticle and on her eggs. 3 MeC31 regulates worker reproduction by inhibiting ovarian development. Most monomethyl-branched hydrocarbons can exist in two stereoisomeric forms. The correct stereochemistry is fundamental to the activity of most bioactive molecules, but this has rarely been investigated for methyl-branched hydrocarbons. Here, we tested the bioactivity of the (S)- and (R)-enantiomers of 3-MeC31, and found that whereas both enantiomers were effective in suppressing worker ovarian development, (S)-3-MeC31 appeared to be more effective at suppressing aggressive behavior by workers. This suggests that the natural pheromone may be a mixture of the two enantiomers. The enantiomeric ratio produced by queens remains unknown because of the small amounts of the compound available from each queen. PMID- 26994183 TI - Sperm chemotaxis promotes individual fertilization success in sea urchins. AB - Reproductive success fundamentally shapes an organism's ecology and evolution, and gamete traits mediate fertilization, which is a critical juncture in reproduction. Individual male fertilization success is dependent on the ability of sperm from one male to outcompete the sperm of other males when searching for a conspecific egg. Sperm chemotaxis, the ability of sperm to navigate towards eggs using chemical signals, has been studied for over a century, but such studies have long assumed that this phenomenon improves individual male fitness without explicit evidence to support this claim. Here, we assessed fertilization changes in the presence of a chemoattractant-digesting peptidase and used a microfluidic device coupled with a fertilization assay to determine the effect of sperm chemotaxis on individual male fertilization success in the sea urchin Lytechinus pictus We show that removing chemoattractant from the gametic environment decreases fertilization success. We further found that individual male differences in chemotaxis to a well-defined gradient of attractant correlate with individual male differences in fertilization success. These results demonstrate that sperm chemotaxis is an important contributor to individual reproductive success. PMID- 26994184 TI - Quantification of sarcomere length distribution in whole muscle frozen sections. AB - Laser diffraction (LD) is a valuable tool for measuring sarcomere length (Ls), a major determinant of muscle function. However, this method relies on few measurements per sample that are often extrapolated to whole muscle properties. Currently it is not possible to measure Ls throughout an entire muscle and determine how Ls varies at this scale. To address this issue, we developed an actuated LD scanner for sampling large numbers of sarcomeres in thick whole muscle longitudinal sections. Sections of high optical quality and fixation were produced from tibialis anterior and extensor digitorum longus muscles of Sprague Dawley rats (N=6). Scans produced two-dimensional Ls maps, capturing >85% of the muscle area per section. Individual Ls measures generated by automatic LD and bright-field microscopy showed excellent agreement over a large Ls range (ICC>0.93). Two-dimensional maps also revealed prominent regional Ls variations across muscles. PMID- 26994185 TI - Effects of seasonal acclimatization on temperature dependence of cardiac excitability in the roach, Rutilus rutilus. AB - Temperature sensitivity of electrical excitability is a potential limiting factor for performance level and thermal tolerance of excitable tissues in ectothermic animals. To test whether the rate and rhythm of the heart acclimatize to seasonal temperature changes, thermal sensitivity of cardiac excitation in a eurythermal teleost, the roach (Rutilus rutilus), was examined. Excitability of the heart was determined from in vivo electrocardiograms and in vitro microelectrode recordings of action potentials (APs) from winter and summer roach acclimatized to 4 and 18 degrees C, respectively. Under heat ramps (3 degrees C h(-1)), starting from the acclimatization temperatures of the fish, heart rate increased to maximum values of 78+/-5 beats min(-1) (at 19.8+/-0.5 degrees C) and 150+/-7 beats min(-1) (at 28.1+/-0.5 degrees C) for winter and summer roach, respectively, and then declined in both groups. Below 20 degrees C, heart rate was significantly higher in winter than in summer roach (P<0.05), indicating positive thermal compensation. Cardiac arrhythmias appeared with rising temperature as missing QRS complexes, increase in variability of heart rate, episodes of atrial tachycardia, ventricular bradycardia and complete cessation of the heartbeat (asystole) in both winter and summer roach. Unlike winter roach, atrial APs of summer roach had a distinct early repolarization phase, which appeared as shorter durations of atrial AP at 10% and 20% repolarization levels in comparison to winter roach (P<0.05). In contrast, seasonal acclimatization had only subtle effects on ventricular AP characteristics. Plasticity of cardiac excitation appears to be necessary for seasonal improvements in performance level and thermal resilience of the roach heart. PMID- 26994186 TI - Evidence for a role of heme oxygenase-1 in the control of cardiac function in zebrafish (Danio rerio) larvae exposed to hypoxia. AB - Carbon monoxide (CO) is a gaseous neurotransmitter produced from the breakdown of heme via heme oxygenase-1 (HO-1; hypoxia-inducible isoform) and heme oxygenase-2 (HO-2; constitutively expressed isoform). In mammals, CO is involved in modulating cardiac function. The role of the HO-1/CO system in the control of heart function in fish, however, is unknown and investigating its physiological function in lower vertebrates will provide a better understanding of the evolution of this regulatory mechanism. We explored the role of the HO-1/CO system in larval zebrafish (Danio rerio) in vivo by investigating the impact of translational gene knockdown of HO-1 on cardiac function. Immunohistochemistry revealed the presence of HO-1 in the pacemaker cells of the heart at 4 days post fertilization and thus the potential for CO production at these sites. Sham treated zebrafish larvae (experiencing normal levels of HO-1) significantly increased heart rate (fH) when exposed to hypoxia (PwO2 =30 mmHg). Zebrafish larvae lacking HO-1 expression after morpholino knockdown (morphants) exhibited significantly higher fH under normoxic (but not hypoxic) conditions when compared with sham-treaded fish. The increased fH in HO-1 morphants was rescued (fH was restored to control levels) after treatment of larvae with a CO-releasing molecule (40 umol l(-1) CORM). The HO-1-deficient larvae developed significantly larger ventricles and when exposed to hypoxia they displayed higher cardiac output ([Formula: see text]) and stroke volume (SV). These results suggest that under hypoxic conditions, HO-1 regulates [Formula: see text] and SV presumably via the production of CO. Overall, this study provides a better understanding of the role of the HO-1/CO system in controlling heart function in lower vertebrates. We demonstrate for the first time the ability for CO to be produced in presumptive pacemaker cells of the heart where it plays an inhibitory role in setting the resting cardiac frequency. PMID- 26994187 TI - When navigating wood ants use the centre of mass of a shape to extract directional information from a panoramic skyline. AB - Bees and ants can control their direction of travel within a familiar landscape using the information available in the surrounding visual scene. To learn more about the visual cues that contribute to this directional control, we have examined how wood ants obtain direction from a single shape that is presented in an otherwise uniform panorama. Earlier experiments revealed that when an ant's goal is aligned with a point within a prominent shape, the ant is guided by a global property of the shape: it learns the relative areas of the shape that lie to its left and right when facing the goal and sets its path by keeping the proportions at the memorised value. This strategy cannot be applied when the direction of the goal lies outside the shape. To see whether a different global feature of the shape might guide ants under these conditions, we trained ants to follow a direction to a point outside a single shape and then analysed their direction of travel when they were presented with different shapes. The tests indicate that ants learn the retinal position of the centre of mass of the training shape when facing the goal and can then guide themselves by placing the centre of mass of training and test shapes in this learnt position. PMID- 26994188 TI - mRNA expression in different developmental stages of the chicken bursa of Fabricius. AB - The bursa of Fabricius, the central humoral immune organ unique to birds, plays an important role in B-lymphocyte differentiation. In order to gain a better understanding of the molecular mechanism of critical biological processes like B cell immigration, differentiation, and final emigration, the transcriptional changes during embryonic and posthatch development of this organ were investigated. We generated a cDNA library from total RNA isolated from 3 representative developmental stages (embryonic day [ED] 10, posthatch d 2 and d 21). We generated over 70 million high-quality reads from the cDNA library by using deep sequencing. The uniquely mapped sequences of ED 10, d 2 and d 21 were 71087280, 59167491 and 70263675 respectively. All of the differential expressed genes were involved in Vitamin A metabolism, regulation of actin cytoskeleton, Wnt signaling pathway, MAPK signaling pathway, Jak-STAT signaling pathway, Notch signaling pathway, Toll-like receptor signaling pathway. The RNA-seq analysis provides a powerful method for analyzing the transcriptome and investigating the transcriptional changes of different development stages of bursa of Fabricius. The assembled bursa transcriptome provides an essential resource for future investigations about chicken Bursa development. PMID- 26994189 TI - Digestibility and metabolism of dietary guanidino acetic acid fed to broilers. AB - In two feeding experiments the retention of supplemental guanidine acetic acid (GAA) in broilers was investigated. In both experiments, the same three treatments were used; the basal feed was supplemented with 0, 0.6, or 6.0 g GAA per kg of feed. While in a growth study (experiment 1) day-old, male Ross 308 broilers were fed diets for 35 days, these diets were fed for only 8 days to fistulated broilers 34 days of age in a balance study (experiment 2). Feeding 0.6 g/kg GAA did not improve growth performance whereas 6.0 g/kg GAA resulted in a reduction of feed consumption and consequently of weight gain (P <= 0.05). Feed conversion was not affected and was 1.48 to 1.49 in all treatments. Increasing levels of dietary GAA gradually increased the creatine concentration in breast muscle and liver tissues (P <= 0.05) indicating a transformation and retention of dietary GAA as creatine. In experiment 2 the non-supplemented basal diet allowed us to determine the endogenous GAA, creatine, and creatinine excretions. Accordingly, only small amounts of these metabolites were recovered in feces while they were much higher in urine. Increasing dietary GAA intake increased fecal and renal GAA, creatine, and creatinine excretion and was significant (P <= 0.05) at 6.0 g/kg dietary GAA compared to no or 0.6 g/kg GAA supplementation. The mean true fecal digestibility of GAA (99%) was unaffected by the level of supplemental GAA. Considering renal GAA excretions, true availability of supplemental GAA was reduced with increasing dose (83% vs. 71%; P <= 0.05). Taking into account creatine and creatinine excretions above those of the basal diet, as they are a consequence of increasing dietary supply, true availability of supplemental GAA shrank from 76% (0.6 g/kg GAA) to 46% (6.0 g/kg GAA; P <= 0.05). Changes in blood creatine and creatinine levels reflected the changes observed in the liver and muscle tissues and may suggest increased transport to excretion organs. Data from these experiment were used to estimate the creatine requirement. PMID- 26994190 TI - Effects of equol on H2O2-induced oxidative stress in primary chicken intestinal epithelial cells. AB - This experiment investigated the antioxidant effects of equol on oxidative stress induced by H2O2 in chicken intestinal epithelial cells (IEC). IEC, from Lingnan yellow broiler chick embryos at embryonic day 18, were cultured in Dulbecco's modified Eagle's medium/F12. Cells were pretreated with 0, 10, 100, or 500 nM equol for 24 h before exposure to 300 MUM H2O2 during a further 24 h. Oxidative damage was assessed by photomicrographs of cells, measuring cell proliferation, malondialdehyde (MDA) content, and antioxidative capacity from cellular total superoxide dismutase (T-SOD) activity, as well as the relative expressions of Nrf2, Bcl-2, SOD-1, GSH-Px3, Claudin-1 Treatment with 300 MUM H2O2 caused serious damage to cells, with fewer normal intestinal epithelial cells, revealed by photomicroscopy. Treatment with 300 MUM H2O2 significantly decreased live cell numbers compared with controls and prior treatment with equol had no effect in offsetting this action of H2O2 (P > 0.05). Compared with the cells treated just with H2O2, pre-treatment with 10, 100 and 500 nM equol significantly enhanced T SOD activity (P < 0.05), while 10 and 100 nM equol before H2O2 significantly enhanced T-SOD activity compared with the untreated controls (P < 0.05). In cells pre-treated with 100 nM equol, the relative abundance of Nrf2 transcripts increased from the controls (P < 0.05) but expressions of Bcl-2, GSH-Px3, or SOD 1 were unaffected (P > 0.05). Pre-treatment with 10 and 100 nM equol significantly increased the transcript abundance of Claudin-1 (P < 0.05). Equol is shown here to protect IECs from oxidative damage by promoting the expression of antioxidant genes, increasing the activities of antioxidant enzymes, and by enhancing antioxidant capacity; 100 nM equol appeared to be the most effective concentration. PMID- 26994191 TI - The cysteine, total sulfur amino acid, tyrosine, phenylalanine + tyrosine, and non-essential amino acid maintenance requirements of broiler breeders. AB - Two hundred and fifty Cobb-Vantress broiler breeders were used to determine the maintenance requirement and efficiency of utilization of dietary Cys, Tyr, and non-essential amino acids (AA) in a 21-day experiment. The breeders were fed crystalline amino acid diets containing graded levels of Cys or Tyr representing 0, 10, 20, 30, and 40% of their suggested requirement level with all other amino acids maintained at 40% of their suggested requirement level. To determine the non-essential AA maintenance requirement, graded levels of non-essential AA were provided by glutamic acid to represent 12, 19, 26, 33, and 40% of the ideal level of glutamic acid with all other amino acids maintained at their maintenance requirement level. The total sulfur amino acid (TSAA) and Phe + Tyr requirements were calculated by combining Cys and Tyr results, respectively, with previously determined Met and Phe, respectively. The slope of Cys, Tyr, and non-essential AA accretion regression line indicated that 29% Cys, 24% TSAA, 21% Tyr, 20% Phe + Tyr, and 9% non-essential AA of crystalline amino acids were retained. The Cys requirement for zero protein accretion was calculated to be 30.48 mg/d or 17.006 mg/ kgBW(0.75)/d or 75.426 mg/kgCP/d. The TSAA requirement for zero accretion was calculated to be 132.25 mg/b/d, 71.48 mg/kgBW(0.75)/d, and 307.55 mg/kgCP/d. The Tyr requirement for zero protein accretion was calculated to be 65.907 mg/d or 37.233 mg/ kgBW(0.75)/d or 175.566 mg/kgCP/d. The Phe + Tyr requirement for zero protein accretion was calculated to be 352.18 mg/b/d, 190.37 mg/kgBW(0.75)/d, and 749.33 mg/kgCP/d. The non-essential AA requirement for zero protein accretion was calculated to be 3715.194 mg/d or 2003.155 mg/kgBW(0.75)/d or 9452.954 mg/kgCP/d. PMID- 26994192 TI - Changes in DNA Methylation and Chromatin Structure of Pro-inflammatory Cytokines Stimulated by LPS in Broiler Peripheral Blood Mononuclear Cells. AB - The pro-inflammatory cytokines IL-1beta, IL-6, and tumor necrosis factor (TNF) alpha mediate inflammation, which is a protective response by body to ensure removal of detrimental stimuli, as well as a healing process for repairing damaged tissue. The overproduction of pro-inflammatory cytokines can induce autoimmune diseases and can be fatal. The aim of this study was to investigate epigenetic mechanisms in the regulation of pro-inflammatory cytokines expression after lipopolysaccharide (LPS) stimulation of broiler peripheral blood mononuclear cells (PBMC). Gene expression, promoter DNA methylation, and chromatin accessibility of pro-inflammatory cytokines in untreated and LPS treated PBMC were compared. The expression of epigenetic enzymes DNA methyltransferase (DNMT) 1, histone deacetylase (HDAC), and histone acetylase (HAT) were measured after LPS stimulation. The results showed the activated gene expression of pro-inflammatory cytokines in broiler PBMC stimulated 3 h by LPS. The demethylation of IL-6 gene - 302 and -264 cytosine-guanine (CpG) sites, as well as TNF-alpha gene -371 CpG site, occurred after LPS treatment (P < 0.05), whereas the methylaiton pattern in the IL-1beta gene promoter region was not affected. Otherwise, LPS stimulation relaxed the chromatin structure at IL-1beta and IL-6 promoter (P < 0.05). The lower expression of DNMT1 and HDAC2, and higher expression of p300-CBP-associated factor and tat-interaction protein-60, were detected in response to LPS (P < 0.05). Our data indicated that after LPS stimulation for 3 h, IL-1beta and IL-6 promoter are remodeled into an accessible structure, and the IL-6 and TNF-alpha promoter are demethylated at special sites, which possible impact the mRNA expression of pro-inflammatory cytokines. PMID- 26994193 TI - Effects of dietary canthaxanthin and 25-hydroxycholecalciferol supplementation on the antioxidant status and tibia quality of duck breeders and newly hatched ducklings. AB - This study evaluated the effects of dietary canthaxanthin (CX) and 25 hydroxycholecalciferol (25-OH-D3) supplementation on the antioxidant status and tibia quality of duck breeders and newly hatched ducklings. In total, 780 female and 156 male duck breeders were randomly allotted to 2 treatments. Duck breeders were fed either a commercial diet (containing 3,000 IU/kg vitamin D3) or the same diet plus a mixture of CX (6 mg/kg) and 25-OH-D3 (0.069 mg/kg) for 40 wk. The antioxidant status of duck breeders, egg yolk, and ducklings; tibia quality of duck breeders and ducklings; and shell quality of breeder eggs were investigated. The total antioxidant capacity of breeder female liver (P = 0.028), breeder male testis (P = 0.049), egg yolk (P = 0.032), one-day-old duckling liver (P = 0.024), and one-day-old duckling yolk sac (P = 0.012) were increased by dietary supplementation of the mixture of CX and 25-OH-D3 The inclusion of CX and 25-OH D3 decreased liver protein carbonyl of breeder females (P = 0.030), and liver malonaldehyde (P = 0.050) and protein carbonyl (P = 0.030) of breeder males. Yolk (P < 0.001), shank (P < 0.001), and yolk sac pigmentation (P < 0.001) of one-day old ducklings were increased by the supplementation of the CX and 25-OH-D3 mixture. No differences (P > 0.05) were observed in tibia quality or eggshell quality between treatments. In conclusion, the inclusion of the mixture of CX and 25-OH-D3 in a diet sufficient in vitamin D3 increased antioxidant status but not tibia quality of duck breeders and newly hatched ducklings. PMID- 26994194 TI - The impact of graded levels of day length on turkey health and behavior to 18 weeks of age. AB - The impact of graded levels of day length on turkey health and behavior was determined in hens and toms raised to 18 wk of age. Birds were allocated to one of 4 lighting treatments (trt) providing 14 (14L), 17 (17L), 20 (20L), and 23 (23L) h of day length. Two time-replicated trials were completed with each, providing 2 rooms per lighting trt and each room having 3 hen (n = 720) and 3 tom (n = 480) pens. Data collection included gait score (GS), the incidence of footpad dermatitis (FPD), breast buttons and blisters, ocular size and pressure (males only), and behavioral observations (males only). Data were analyzed using SAS 9.3 based on a completely randomized design nested within 4 lighting trt. Regression analysis established relationships between response criteria and day length. Differences were considered significant at P <= 0.05 and trends noted at P <= 0.10. Gait score, FPD, and the incidence of breast buttons and blisters were assessed on 5 birds per pen at 11 and 17 wk of age. Average GS increased linearly with day length at 11 and 17 wk for both hens and toms, but the effect was larger in toms. Day length did not affect FPD, but more lesions and severe scores were found for hens than toms. The presence of breast buttons and blisters increased linearly with day length (11 wk) with the effect on blisters predominately seen in toms. Eye weight and size increased with increasing day length at 12 and 18 wk. Ocular pressure was not affected by day length. Infrared cameras recorded tom behavior over a 24 h period, and behaviors were classified over 10-min intervals using a scan sampling technique at 11 and 17 wk. Alterations in behavioral repertoire were observed with a linear increase in inactive resting and a linear decrease in standing, walking, preening, and environmental and feather pecking behaviors with increased day length. To conclude, day length affected bird mobility and incidence of breast blisters in an age- and gender-specific manner, and time spent inactive increased with longer day length. PMID- 26994195 TI - Effects of replacing corn with sorghum on the performance of overfed mule ducks. AB - The aim of this trial was to study the effects of replacing yellow corn (C) with condensed tannin-free sorghum (S) during the finishing period (F period; age 53 to 79 d) and/or overfeeding period (O period; age 80 to 91 d) on the performance of overfed mule ducks. 192 ducks were divided into 4 groups (48 in each) differing in the cereal (yellow corn or sorghum) included in the diet given during the F and/or the O periods, using a 2 * 2 factorial arrangement of treatments : SS, SC, CS, CC. At the end of the O period, the birds were slaughtered after 10 h of fasting to measure foie gras and magret qualities. Mortality (1%; P > 0.05) and weight gain (2,030 g; P > 0.05) during the O period were similar in the 4 groups. At the end of the O period, birds overfed with sorghum had foie gras that was heavier (723 vs. 694 g in CS+SS vs. CC+SC, respectively; P < 0.05) and less yellow (24.40 vs. 38.59 for b* in CS+SS vs. CC+SC, respectively; P < 0.001) than birds overfed with corn. Fat loss during foie gras cooking was similar in the 4 groups (18%; P > 0.05), but the foie gras was less yellow in birds overfed with sorghum (14.84 vs. 26.01 for b* in CS+SS vs. CC+SC, respectively; P < 0.001). Weight of magret was similar in the 4 groups (491 g, P > 0.05) but the color of the breast muscle and skin of magret was less yellow in birds overfed with sorghum compared with corn (12.26 vs. 12.92 and 13.84 vs. 18.30 in CS+SS vs. CC+SC, respectively; P < 0.001). In conclusion, the replacement of yellow corn with sorghum during finishing and/or overfeeding is possible and useful in a mule duck foie gras production system because it increases foie gras weight without decreasing the weight of magret However, it changes the quality of the products, mainly their color. PMID- 26994196 TI - Incubation temperature alters thermal preference and response to heat stress of broiler chickens along the rearing phase. AB - The current study aimed to investigate whether embryonic temperature manipulation may alter thermal preference throughout the rearing phase of broiler chickens and how this manipulation may affect response to thermal challenge, metabolism, growth rate and feed intake rate. Eggs were exposed to a constant incubation temperature [machine temperatures: 36 degrees C (Low), 37.5 degrees C (Control), and 39 degrees C (High); eggshell temperature of 37.4 +/- 0.08 degrees C, 37.8 +/ 0.15 degrees C, and 38.8 +/- 0.33 degrees C, respectively] from d 13 till hatching. Low treatment chickens showed lower plasma T3 and GH levels at d 1 of age and lower T3 level at d 42 of age compared to the Control treatment. Preferred ambient, rectal temperature, T4 level, growth rate, food intake rate, and response to thermal challenge were not altered in these chickens. On the other hand, High-treatment chickens exhibited high preferred ambient temperature and rectal temperature during the first 2 wk post-hatch, lower plasma T3 level at d 21 and 42 and a delayed increase in respiratory movement in response to thermal challenge compared to the Control treatment. However, chickens subjected to the Control and High treatments did not differ in T4 and GH level and performance. We conclude that exposure to high temperature during late embryonic development has long-lasting effects on the thermoregulatory system of broiler chickens by affecting the heat tolerance of these chickens. Moreover, the preferred ambient temperature of the chickens from heat-treated eggs correspond to those recommended for the strain under study, whereas for the cold-treated and control chickens it was 1 degrees C below, indicating that incubation temperature might have consequences on the ambient temperature chickens require during the rearing phase. PMID- 26994197 TI - Origin and genetic diversity of Egyptian native chickens based on complete sequence of mitochondrial DNA D-loop region. AB - Domestic chickens (Gallus gallus) play a significant role, ranging from food and entertainment to religion and ornamentation. However, the details on their domestication process are still controversial, especially the origin and evolution of African chickens. Egypt is thought to be important place for this event because of its geographic location as well as its long history of civilization. However, the genetic component and structure of Egyptian native chicken (ENC) have not been studied so far. The aim of this study is to clarify the origin and evolution of African chickens through assessing the genetic diversities and structure of five ENC breeds using the mitochondrial D-loop sequences. Our results suggest there is genetic differentiation between the pure native breeds and the improved native breeds. The latter breeds were established by the hybridization of the pure native and the exotic breeds. The pure native breeds were estimated to be established about 800 years ago. Subsequently, we extensively analyzed the D-loop sequences from the ENC as well as the globally collected chickens (2,010 individuals in total). Our phylogenetic tree among the regional populations shows African chickens can be separated to two distinct clades. The first clade consists of North African (Egypt), Central African (Sudan and Cameroon), European, and West (and Central) Asian chickens. The second clade consists of East African (Kenya, Malawi, and Zimbabwe) and Pacific chickens. It suggests the dual origins of African native chickens. The first group was probably originated from South Asia, and then migrated to West Asia, and finally arrived to Africa thorough Egypt. The second group migrated from Pacific to East Africa via Indian Ocean probably by Austronesian people. This dual origin hypothesis as well as estimated divergence times in this study is harmonious with the archaeological and historical evidences. Our migration analysis suggests there is limited gene flow within African continent. These obtained findings are important for the better understanding of the diversity and uniqueness of African native chickens. PMID- 26994198 TI - Developing control points for halal slaughtering of poultry. AB - Halal (permissible or lawful) poultry meat production must meet industry, economic, and production needs, and government health requirements without compromising the Islamic religious requirements derived from the Qur'an and the Hadiths (the actions and sayings of the Prophet Muhammad, peace and blessings be upon him). Halal certification authorities may vary in their interpretation of these teachings, which leads to differences in halal slaughter requirements. The current study proposes 6 control points (CP) for halal poultry meat production based on the most commonly used halal production systems. CP 1 describes what is allowed and prohibited, such as blood and animal manure, and feed ingredients for halal poultry meat production. CP 2 describes the requirements for humane handling during lairage. CP 3 describes different methods for immobilizing poultry, when immobilization is used, such as water bath stunning. CP 4 describes the importance of intention, details of the halal slaughter, and the equipment permitted. CP 5 and CP 6 describe the requirements after the neck cut has been made such as the time needed before the carcasses can enter the scalding tank, and the potential for meat adulteration with fecal residues and blood. It is important to note that the proposed halal CP program is presented as a starting point for any individual halal certifying body to improve its practices. PMID- 26994199 TI - Performance, immunity, and physiological responses of broilers to dietary energy and protein sequential variations. AB - The current trial was designed to examine effects of sequential feeding of diets varying in energy and protein contents on performance, gut development, welfare indices, and immune responses of broiler chicks. A total of 240 one-day-old broiler chicks (Ross 308) were randomly allotted to 4 treatments with 5 replicates in a completely randomized design. Sequential feeding was evaluated in 48-h cycles during 8 to 28 d of age. Diets varied in energy (E+ = 3,210 kcal/kg and E- = 2,790 kcal/kg) and protein (P+ = 25.14% CP and P- = 16.76% CP) contents. The 4 feeding programs were: control (ME: 3,000 kcal/kg, CP: 20.95%); P+/P- (P+ followed by P- containing 3,000 kcal/kg energy); E-/E+ (E- followed by E+ containing 20.95% CP), and E-P+ / E+P- (E-P+ followed by E+P-). The experiment lasted 42 d and birds were fed by a standard finishing diet from d 28 to 42. Broilers fed on E-/E+ and E-P+/E+P- had lower daily feed intake than control ones during 8 to 28 d of age (P < 0.05), while daily weight gain and feed conversion ratio were not affected significantly. Footpad dermatitis was lower in birds sequentially fed E-/E+ and E-P+/E+P- at 35 d of age (P < 0.05). Sequential feeding of diets varying in either energy or protein or both increased duration of tonic immobility at d 39 of age (P < 0.05). Feeding with E-/E+ regime decreased jejunal crypt depth, while feeding P+/P- regime increased villus height and crypt depth in the duodenum and ileum (P < 0.05). However, no relationship was found between intestinal morphology and growth performance of broiler chickens. Antibody production against sheep red blood cells as well as Newcastle and influenza disease viruses was not affected by sequential feeding. In conclusion, digestive organs and intestinal morphology might be adjusted to energy and protein variations. Sequential feeding increased the fear level in chickens. PMID- 26994200 TI - Egg production and welfare of laying hens kept in different housing systems (conventional, enriched cage, and free range). AB - The aim of this study was to compare egg production performance and welfare traits of laying hens kept in conventional cage (CC), enriched cage (EC), and free range (FR). Lohmann Brown laying hens (n = 480 with 160 per housing type) were studied across a production cycle from placement at 17 wk until depopulation at 66 wk. The hens were randomly allocated into cages or pens of housing system groups; within each system there were four replicates with 40 hens in each pen or cage. The hen day egg production (P = 0.037), feed intake (FI) (P < 0.001), egg mass (EM) (P < 0.001), and dirty egg ratio of hens were higher in the FR system but similar in the CC and EC systems. The highest mortality ratio was found in EC system hens (P = 0.020). The best feather score was found in FR system hens (P < 0.001). The worse body wound score was found in EC system hens (P = 0.038). On the other hand, the worse bumble foot and footpad lesions were found in FR system hens (P < 0.001). The highest tibia breaking strength was found in FR system hens compared with in CC and EC system hens (P < 0.001). The highest Heterophil/Lymphocyte ( H/L: ) ratio was found in CC system hens (P = 0.006) but the blood phosphorus ( P: ) level was higher in FR system hens (P = 0.013). The tonic immobility, blood glucose, total cholesterol, triglyceride, and Ca values of hens were found to be similar in all systems (P > 0.05). The hens in the FR system had additional space for optimum comfort and better feather and bone traits, but the dirty egg ratio, feed consumption, and foot lesions were higher than in CC and EC systems. PMID- 26994201 TI - Environmental assessment of three egg production systems - Part III: Airborne bacteria concentrations and emissions. AB - Airborne microorganism level is an important indoor air quality indicator, yet it has not been well documented for laying-hen houses in the United States. As a part of the Coalition for Sustainable Egg Supply (CSES) environmental monitoring project, this study comparatively monitored the concentrations and emissions of airborne total and Gram-negative (Gram(-)) bacteria in three types of commercial laying-hen houses, i.e., conventional cage (CC), aviary (AV), and enriched colony (EC) houses, over a period of eight months covering the mid and late stages of the flock cycle. It also delineated the relationship between airborne total bacteria and particulate matter smaller than 10 MUm in aerodynamic diameter (PM10). The results showed airborne total bacteria concentrations (log CFU/m(3)) of 4.7 +/- 0.3 in CC, 6.0 +/- 0.8 in AV, and 4.8 +/- 0.3 in EC, all being higher than the level recommended for human environment (3.0 log CFU/m(3)). The much higher concentrations in AV arose from the presence of floor litter and hen activities on it, as evidenced by the higher concentrations in the afternoon (with litter access) than in the morning (without litter access). The overall means and standard deviation of airborne total bacteria emission rates, in log CFU/[h-hen] (or log CFU/[h-AU], AU = animal unit or 500 kg live weight) were 4.8 +/- 0.4 (or 7.3 +/- 0.4) for CC, 6.1 +/- 0.7 (or 8.6 +/- 0.7) for AV, and 4.8 +/- 0.5 (or 7.3 +/- 0.5) for EC. Both concentration and emission rate of airborne total bacteria were positively related to PM10 Gram(-) bacteria were present at low concentrations in all houses; and only 2 samples (6%) in CC, 7 (22%) samples in AV, and 2 (6%) samples in EC out of 32 air samples collected in each house were found positive with Gram(-) bacteria. The concentration of airborne Gram(-) bacteria was estimated to be <2% of the total bacteria. Total bacteria counts in manure on belt (in all houses) and floor litter (only in AV) were similar; however, the manure had much more Gram(-) bacteria than the litter. The results point out the need to mitigate airborne total bacteria in laying-hen houses, especially in AV houses. PMID- 26994202 TI - Effect of storage duration on the rheological properties of goose liquid egg products and eggshell membranes. AB - In practice, goose eggs are increasingly used and, therefore, the rheological properties have to be known for processing. The eggs of geese (Landes Goose, Anser anser f. domestica) were stored for one, 2, 3, 4, 6, and 8 wk at a constant temperature 4 degrees C. First of all, the egg quality parameters were described in terms of egg weight, egg weight loss, egg shape index, yolk height, albumen height, yolk index, albumen index, and Haugh units. In the next step the rheological behavior of liquid egg products (egg yolk, albumen, and whole liquid egg) was studied using a concentric cylinder viscometer. Flow curves of all liquid egg products exhibited non-Newtonian shear thinning behavior. This behavior can be described using the Herschel-Bulkley model and for technical application using the Ostwald-de Waele model. The effect of the storage duration on the rheological behavior is different for the different liquid egg products. With the exception of very low shear rates, the viscosity of the egg yolk as well as of the whole liquid egg decreases with storage time. At lower shear rates there is a tendency toward increased albumen viscosity with storage duration. The storage duration also affects the mechanical properties of the eggshell membrane. This effect has been evaluated in terms of the ultimate tensile strength, fracture strain, and fracture toughness. All these parameters increased with the loading rate, but decreased during the egg storage. These mechanical phenomena should be respected, namely in the design of the egg model for the numerical simulation of the egg behavior under different kinds of the mechanical loading. PMID- 26994203 TI - Salmonella enterica serovar Typhimurium utilizes the ClpPX and Lon proteases for optimal fitness in the ceca of chickens. AB - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a leading cause of salmonellosis. Poultry and poultry products are implicated in transmission of Salmonella to humans. In 2013, an outbreak of S Typhimurium occurred that comprised 39 states within the United States and was associated with backyard flocks of chickens. Colonization of the avian host by S Typhimurium requires numerous genetic factors encoded within the bacterium. Of particular interest are genetic factors induced by alternative sigma factors within S Typhimurium since these genetic elements are important for adaptation to different environmental stresses. The heat shock response is a dedicated change in gene regulation within bacteria in response to several stresses, specifically growth at 42 degrees C. Because chickens have a higher body temperature than other animals (42 degrees C) the hypothesis was tested that components of the heat shock response are important for optimal fitness within the chicken. To this end, deletion of the heat shock proteases clpPX (BTNC0022) or lon (BTNC0021) was accomplished and the bacterial fitness in vivo was compared to the "wild-type" strain (NC1040) using a competition assay. One-day-old chicks were orally gavaged with an equal mixture of NC1040 and either BTNC0022 or BTNC0021. Quantification of viable bacteria over time by using plate counts indicated that deletion of either heat shock protease resulted in significantly reduced colonization of the chicken ceca compared to the wild-type strain. To satisfy the molecular Koch's postulates, clpPX and lon mutants were complemented in trans using a low-copy number plasmid for additional in vivo experiments. Complementation studies confirmed the importance of either heat shock protease to colonization of the chicken ceca. This report demonstrated that both ClpPX and Lon were important for optimal fitness within chickens. Moreover, these results suggested that components of the heat shock may be critical factors used by S. Typhimurium for colonization of poultry. The use of feed additives or other treatments that inactivate or inhibit ClpPX or Lon may reduce the bacterial burden of S. Typhimurium in poultry. PMID- 26994204 TI - Nutritive value of cold-pressed camelina cake with or without supplementation of multi-enzyme in broiler chickens. AB - The objectives were to determine the standardized ileal digestibility (SID) of amino acids (AA) and AMEn value of cold-pressed camelina cake (CPCC) and the effect of adding multi-enzyme to a corn-CPCC diet for broilers. The 600 male broiler chicks were divided into 40 groups and fed 5 diets in a completely randomized design (8 groups per diet) from d 15 to d 21 of age. A corn basal diet and the basal diet with 30% of it replaced by CPCC were used in a 2 * 2 factorial arrangement with or without multi-enzyme (2,800 U of cellulase, 1,800 U of pectinase, 400 U of mannanase, 50 U of galactanase, 1,000 U of xylanase, 600 U of glucanase, 2,500 U of amylase, and 200 U of protease/kilogram of diet; Superzyme OM, 1 g/kg). The fifth diet was N-free. The corn basal diet was fed to determine nutrient digestibility and retention for CPCC by substitution. The N-free diet was fed to estimate basal endogenous AA losses for determining SID of AA. Diets contained TiO2 as indigestible marker. On a DM basis, CPCC contained 39.8% CP, 38.3% neutral detergent fiber, 12.7% ether extract, 1.89% Lys, 0.70% Met, 1.56% Thr, and 0.45% Trp. The SID of Lys, Met, Thr, and Trp for CPCC were 76.5, 85.5, 72.8, and 84.1%, respectively. The AMEn value for CPCC was 1,671 kcal/kg of DM. Multi-enzyme supplementation increased (P < 0.05) the SID of Met and Thr and the AMEn value of the corn-CPCC-based diet by 1.4, 1.3, and 3.0%, respectively. The multi-enzyme increased (P = 0.026) the AMEn value of CPCC from 1,671 to 1,941 kcal/kg of DM. In conclusion, the CPCC evaluated in the present study can be included in poultry diets as a source of energy and AA. Multi-enzyme supplementation increased the AMEn value of CPCC for broilers. PMID- 26994205 TI - Symposium: Animal welfare challenges for today and tomorrow. AB - The increasing separation of the public from production agriculture means there is often a lack of knowledge among consumers about current production practices and a perception that increased productivity and economic efficiency are necessarily associated with a decline in animal welfare. A symposium was organized to present information about animal welfare issues and the challenges they pose for both scientists and the poultry and allied industries. Companion papers provide information about understanding public attitudes and physiological/immunological approaches to welfare assessment, while this paper outlines current and future challenges to egg and meat production and industry responses to those challenges. For broiler chickens, increases in growth rate result in corollary increases in metabolic heat generation and water consumption, leading to the need for continuing improvements in housing, ventilation, and litter management. Stocking densities, lighting programs, muscle myopathies, and use of antibiotics are also areas that require research attention. In the layer industry, the key challenge is housing, with the industry undergoing a shift from conventional cage housing to alternatives like enriched colonies or cage-free. While these alternative systems have hen welfare advantages, there are also welfare disadvantages that require the development of mitigation strategies, and it is also essential to address associated issues including economic, environmental, egg safety, and worker health impacts. Concerns on the horizon include euthanasia of surplus male chicks and spent hens as well as beak trimming. The humaneness of slaughter methods is an important welfare and consumer confidence issue, and the current regulations for poultry slaughter in the USA are discussed and compared to those for livestock. The poultry and allied industries, including retailers, are responding to these concerns by consulting with experts, developing science-based animal care standards and auditing programs, strengthening training and oversight programs, promoting research, and improving communication channels. In future, intensifying multi-disciplinary research efforts and developing mechanisms to improve communication between scientists and stakeholders, including the public, will be critical to addressing these issues. PMID- 26994206 TI - Perch use by laying hens in a commercial aviary. AB - Non-cage housing systems, such as the aviary, are being implemented by the laying hen industry, including in North America, in an attempt to improve the welfare of hens. Perches are a resource that is consistently included in aviaries. Hens are strongly motivated to perch, and perching can improve leg bone strength. However, hens may prefer elevated perches, particularly at night, and thus simply providing perches is not enough to improve welfare; they must be provided in a way that allows all hens to access them. Observations of laying hens using perches and ledges (flat, solid metal shelves to assist hens' movement between tiers) in a commercial aviary revealed variation in where hens roosted within the tiered aviary enclosure across the flock cycle (peak, mid and end of lay; P < 0.001 for all age points). Hens most often preferred roosting in the highest enclosure levels, leading to crowding on upper perches and ledges while perch space remained available on lower levels. Restricted access to preferable perches may cause frustration in hens, leading to welfare issues. Hens roosted more on perches at peak lay than mid and end lay (P < 0.001) but roosted less on ledges at peak lay than mid and end lay (P < 0.001). Additionally, more hens roosted on both perches and ledges in the 'dark' observation period compared with the number of hens roosting during the 'light' observation period (P < 0.001). Further research should look at all structural elements within the system that are used by hens for roosting, such as edges of tiers and upper wire floors, to evaluate how changes in perching preferences across the lay cycle may correlate with system design and bird-based parameters. PMID- 26994207 TI - Welfare indicators in laying hens in relation to nest exclusion. AB - Consumer concerns about the welfare of laying hens are increasing, leading to increased interest in identifying reliable ways to assess welfare. The present study evaluated invasive and non-invasive welfare indicators in relation to a stressful challenge. The study included 126 Lohmann Selected Leghorn hens housed in furnished cages. Welfare indicators were measured between 61 and 70 wk of age in birds excluded from their nests for 5 consecutive d and control birds that had continuous access to nests. Baseline recordings were carried out in both groups prior to and post exclusion period. The assessed indicators were: corticosterone metabolites in droppings (FCM), corticosterone concentration in yolk, corticosterone concentration in plasma, irregularities of eggshells, heterophil to lymphocyte (H:L) ratio, tonic immobility duration, and feather cover. Behavioral observations showed that the birds had a clear preference for using the secluded nest sites, confirming that they were likely to perceive nest exclusion as an undesirable experience. Further, elevated levels of FCM in droppings, yolk corticosterone concentrations, H:L ratios and irregular eggshells were detected in both nest deprived and control birds during the exclusion. This suggests that these indicators were able to detect an increased stress response arising from nest deprivation, and it is hypothesized that the stress spread to birds in adjacent cages with access to nests. There was a positive and consistent correlation between FCM in droppings and eggshell irregularities, also supporting the use of eggshell irregularities as a potential non-invasive welfare indicator. However, the pattern of the stress response varied between indicators and correlations were generally few and inconsistent, highlighting the complexity of the relationship among welfare indicators. PMID- 26994208 TI - Broilers with low serum Mannose-binding Lectin show increased fecal shedding of Salmonella enterica serovar Montevideo. AB - Mannose-binding lectin (MBL) is a key molecule in innate immunity. MBL binds to carbohydrates on the surface of pathogens, initiating the complement system via the lectin-dependent pathway or facilitates opsonophagocytosis. In vivo studies using inbred chicken lines differing in MBL serum concentration indicate that chicken MBL affects Salmonella resistance; further studies are imperative in conventional broiler chickens. In this study 104 conventional day-old chickens (offspring from a cross between Cobb 500 male and female parent breeders) were orally infected with Salmonella enterica subsp. enterica serovar Montevideo. The chickens were divided into two groups based on polymorphisms in their MBL promoter region, designated L/L for low serum concentrations of MBL and L/H for medium serum concentrations of MBL. A semi-quantitative real-time PCR method for detection of Salmonella in cloacal swabs was used, the log10 CFU quantification was based on a standard curve from artificially spiked cloacal swab samples pre incubated for 8 h with known concentrations of Salmonella ranging from 10(1) to 10(6) CFU/swabs, with an obtained amplification efficiency of 102% and a linear relationship between the log10 CFU and the threshold cycle Ct values of (R(2) = 0.99). The L/L chickens had significantly higher Log10 CFU/swab at week 5 post infection (pi) than the L/H chickens. A repetition of the study with 86 L/L and 18 L/H chickens, also gave significantly higher log10 CFU +/- SEM in cloacal swabs, using the semi-quantitative real-time PCR method from L/L chickens than from the L/H chickens at week 5 pi. These results indicate that genetically determined basic levels of MBL may influence S. Montevideo susceptibility. PMID- 26994209 TI - Increased efficacy of inactivated vaccine candidates prepared with Salmonella enterica serovar Typhimurium strains of predominant genotypes in ducks. AB - Salmonella enterica serovar Typhimurium has been a major causative agent of food borne human disease, mainly due to consumption of contaminated food animal products. In particular, ducks serve as a reservoir of serovar Typhimurium, and are one of the common sources of human infection. To prevent infection of ducks, and therefore minimize human infection, it is critical to control the persistent epidemic strains in ducks. Here, we analyzed the genetic diversity and virulence of serovar Typhimurium isolates from ducks in Korea to identify the predominant strains that might be used as efficient vaccine candidates for ducks. Among the isolates, 2 representative isolates (ST26 and ST76) of predominant genotypes were selected as vaccine strains on the basis of genotypic analysis by pulsed-field gel electrophoresis and DNA microarrays. Two-week-old ducks were then injected intramuscularly with inactivated vaccine candidates prepared using ST26 or ST76 (10(8) cfu/0.5 mL/duck or 10(9) cfu/0.5 mL/duck), and oral challenge with a highly virulent serovar Typhimurium strain (10(9) cfu/0.5 mL/duck) was carried out 2 wk later. Shedding of the challenge strain was significantly decreased in group 2 after vaccination. The antibody levels by enzyme-linked immunosorbent assay in all vaccinated groups were enhanced significantly (P < 0.05) compared to the unvaccinated control group. Overall, vaccination with ST26 or ST76 reduced bacterial shedding and colonization in internal organs, and induced elevated antibody response. In particular, serovar Typhimurium ST26 (10(8) cfu/0.5 mL/duck) was the most effective vaccine candidate, which can provide efficient protection against serovar Typhimurium in ducks with higher effectiveness compared to a commercial vaccine currently used worldwide. PMID- 26994210 TI - Inhibition of Abeta(1-40) fibril formation by cyclophilins. AB - Cyclophilins interact directly with the Alzheimer's disease peptide Abeta (amyloid beta-peptide) and are therefore involved in the early stages of Alzheimer's disease. Abeta binding to CypD (cyclophilin D) induces dysfunction of human mitochondria. We found that both CypD and CypA suppress in vitro fibril formation of Abeta(1-40) at substoichiometric concentrations when present early in the aggregation process. The prototypic inhibitor CsA (cyclosporin A) of both cyclophilins as well as the new water-soluble MM258 derivative prevented this suppression. A SPOT peptide array approach and NMR titration experiments confirmed binding of Abeta(1-40) to the catalytic site of CypD mainly via residues Lys(16)-Glu(22) The peptide Abeta(16-20) representing this section showed submicromolar IC50 values for the peptidyl prolyl cis-trans isomerase activity of CypD and CypA and low-micromolar KD values in ITC experiments. Chemical cross-linking and NMR-detected hydrogen-deuterium exchange experiments revealed a shift in the populations of small Abeta(1-40) oligomers towards the monomeric species, which we investigated in the present study as being the main process of prevention of Abeta fibril formation by cyclophilins. PMID- 26994211 TI - Extrapolation of efficacy and other data to support the development of new medicines for children: A systematic review of methods. AB - OBJECTIVE: When developing new medicines for children, the potential to extrapolate from adult data to reduce the experimental burden in children is well recognised. However, significant assumptions about the similarity of adults and children are needed for extrapolations to be biologically plausible. We reviewed the literature to identify statistical methods that could be used to optimise extrapolations in paediatric drug development programmes. METHODS: Web of Science was used to identify papers proposing methods relevant for using data from a 'source population' to support inferences for a 'target population'. Four key areas of methods development were targeted: paediatric clinical trials, trials extrapolating efficacy across ethnic groups or geographic regions, the use of historical data in contemporary clinical trials and using short-term endpoints to support inferences about long-term outcomes. RESULTS: Searches identified 626 papers of which 52 met our inclusion criteria. From these we identified 102 methods comprising 58 Bayesian and 44 frequentist approaches. Most Bayesian methods (n = 54) sought to use existing data in the source population to create an informative prior distribution for a future clinical trial. Of these, 46 allowed the source data to be down-weighted to account for potential differences between populations. Bayesian and frequentist versions of methods were found for assessing whether key parameters of source and target populations are commensurate (n = 34). Fourteen frequentist methods synthesised data from different populations using a joint model or a weighted test statistic. CONCLUSIONS: Several methods were identified as potentially applicable to paediatric drug development. Methods which can accommodate a heterogeneous target population and which allow data from a source population to be down-weighted are preferred. Methods assessing the commensurability of parameters may be used to determine whether it is appropriate to pool data across age groups to estimate treatment effects. PMID- 26994212 TI - Modelling the distribution of health-related quality of life of advanced melanoma patients in a longitudinal multi-centre clinical trial using M-quantile random effects regression. AB - Health-related quality of life assessment is important in the clinical evaluation of patients with metastatic disease that may offer useful information in understanding the clinical effectiveness of a treatment. To assess if a set of explicative variables impacts on the health-related quality of life, regression models are routinely adopted. However, the interest of researchers may be focussed on modelling other parts (e.g. quantiles) of this conditional distribution. In this paper, we present an approach based on quantile and M quantile regression to achieve this goal. We applied the methodologies to a prospective, randomized, multi-centre clinical trial. In order to take into account the hierarchical nature of the data we extended the M-quantile regression model to a three-level random effects specification and estimated it by maximum likelihood. PMID- 26994213 TI - Study duration for three-arm non-inferiority survival trials designed for accrual by cohorts. AB - Study planning is particularly complex for survival trials because it usually involves an accrual period and a continued observation period after accrual closure. The three-arm clinical trial design, which includes a test treatment, an active reference, and a placebo control, is the gold standard design for the assessment of non-inferiority. The existing statistical methods of calculating minimal sample size for non-inferiority trials with three-arm design and survival type endpoints cannot take into consideration the accrual rate of patients to the trial, the length of accrual period, the length of continued observation period after accrual closure, and unbalanced allocation of the total sample size. The purpose of this paper is to develop a statistical method, which allows for all these sources of variability for planning non-inferiority trials with the gold standard design for censored, exponentially distributed time-to-event data. The proposed method is based on the assumption of exponentially distributed failure times and a non-inferiority test formulated in terms of the retention of effect hypotheses. It can be used to calculate the duration of accrual required to assure a desired power for non-inferiority trials with active and placebo control. We illustrate the use of the method by considering a randomized, active- and placebo-controlled trial in depression associated with Parkinson's disease. We then explore the validity of the proposed method by simulation studies. An R language program for the implementation of the proposed algorithm is provided as supplementary material. PMID- 26994214 TI - Detecting influential observations in a model-based cluster analysis. AB - Finite mixture models have been used to model population heterogeneity and to relax distributional assumptions. These models are also convenient tools for clustering and classification of complex data such as, for example, repeated measurements data. The performance of model-based clustering algorithms is sensitive to influential and outlying observations. Methods for identifying outliers in a finite mixture model have been described in the literature. Approaches to identify influential observations are less common. In this paper, we apply local-influence diagnostics to a finite mixture model with known number of components. The methodology is illustrated on real-life data. PMID- 26994215 TI - Missing value imputation for physical activity data measured by accelerometer. AB - An accelerometer, a wearable motion sensor on the hip or wrist, is becoming a popular tool in clinical and epidemiological studies for measuring the physical activity. Such data provide a series of activity counts at every minute or even more often and displays a person's activity pattern throughout a day. Unfortunately, the collected data can include irregular missing intervals because of noncompliance of participants and therefore make the statistical analysis more challenging. The purpose of this study is to develop a novel imputation method to handle the multivariate count data, motivated by the accelerometer data structure. We specify the predictive distribution of the missing data with a mixture of zero-inflated Poisson and Log-normal distribution, which is shown to be effective to deal with the minute-by-minute autocorrelation as well as under- and over-dispersion of count data. The imputation is performed at the minute level and follows the principles of multiple imputation using a fully conditional specification with the chained algorithm. To facilitate the practical use of this method, we provide an R package accelmissing. Our method is demonstrated using 2003-2004 National Health and Nutrition Examination Survey data. PMID- 26994216 TI - Methods for meta-analysis of pharmacodynamic dose-response data with application to multi-arm studies of alogliptin. AB - Standard methods for meta-analysis of dose-response data in epidemiology assume a model with a single scalar parameter, such as log-linear relationships between exposure and outcome; such models are implicitly unbounded. In contrast, in pharmacology, multi-parameter models, such as the widely used Emax model, are used to describe relationships that are bounded above and below. We propose methods for estimating the parameters of a dose-response model by meta-analysis of summary data from the results of randomized controlled trials of a drug, in which each trial uses multiple doses of the drug of interest (possibly including dose 0 or placebo). We assume that, for each randomized arm of each trial, the mean and standard error of a continuous response measure and the corresponding allocated dose are available. We consider weighted least squares fitting of the model to the mean and dose pairs from all arms of all studies, and a two-stage procedure in which scalar inverse-variance meta-analysis is performed at each dose, and the dose-response model is fitted to the results by weighted least squares. We then compare these with two further methods inspired by network meta analysis that fit the model to the contrasts between doses. We illustrate the methods by estimating the parameters of the Emax model to a collection of multi arm, multiple-dose, randomized controlled trials of alogliptin, a drug for the management of diabetes mellitus, and further examine the properties of the four methods with sensitivity analyses and a simulation study. We find that all four methods produce broadly comparable point estimates for the parameters of most interest, but a single-stage method based on contrasts between doses produces the most appropriate confidence intervals. Although simpler methods may have pragmatic advantages, such as the use of standard software for scalar meta analysis, more sophisticated methods are nevertheless preferable for their advantages in estimation. PMID- 26994217 TI - Introduction of Flexible Cyanoacrylates in Sutureless Gastric Closure. AB - Background Clinical effectiveness and safety of biological and synthetic adhesives in digestive closures have been evaluated. Their use is becoming more prevalent, as rigidity and inflexibility are its more remarkable weaknesses. However, little is known about their role in gastric and anastomotic closures. Moreover, usefulness of novel flexible types of synthetic adhesives as n-butyl cyanoacrylate has not been assessed yet. Materials and Methods One centimeter long gastrotomy was performed in 24 male Wistar rats, which were divided depending on the type of closure method employed: manual USP 5/0 silk interrupted suture versus sutureless closure with Histoacryl Flexible (n-butyl-cyanoacrylate with softener) or Histoacryl Double Component (n-butyl-cyanoacrylate with softener and hardener). Microscopic evaluation of the suture viability and integrity was performed, and adhesion formation during the cicatrization process were assessed. During an 8-week follow-up clinical and histopathological aspects as well as hematologic and inflammatory biomarkers were studied. Results No differences among groups where found in any of the clinical, analytical, or histopathological issues assessed except for a higher incidence rate of adhesions in the Histoacryl Double Component group when compared with hand-sewn suture group (P = .04). Our results support experimental studies in large mammals (pigs) for further study of sutureless hollow viscera closure. PMID- 26994218 TI - Effector gammadelta T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors. AB - gammadelta T lymphocytes are programmed into distinct IFN-gamma-producing CD27(+) (gammadelta27(+)) and IL-17-producing CD27(-) (gammadelta27(-)) subsets that play key roles in protective or pathogenic immune responses. Although the signature cytokines are shared with their alphabeta Th1 (for gammadelta27(+)) and Th17 (for gammadelta27(-)) cell counterparts, we dissect in this study similarities and differences in the transcriptional requirements of murine effector gammadelta27(+), gammadelta27(-)CCR6(-), and gammadelta27(-)CCR6(+) gammadelta T cell subsets and alphabeta T cells. We found they share dependence on the master transcription factors T-bet and RORgammat for IFN-gamma and IL-17 production, respectively. However, Eomes is fully dispensable for IFN-gamma production by gammadelta T cells. Furthermore, the Th17 cell auxiliary transcription factors RORalpha and BATF are not required for IL-17 production by gammadelta27(-) cell subsets. We also show that gammadelta27(-) (but not gammadelta27(+)) cells become polyfunctional upon IL-1beta plus IL-23 stimulation, cosecreting IL-17A, IL-17F, IL-22, GM-CSF, and IFN-gamma. Collectively, our in vitro and in vivo data firmly establish the molecular segregation between gammadelta27(+) and gammadelta27(-) T cell subsets and provide novel insight on the nonoverlapping transcriptional networks that control the differentiation of effector gammadelta versus alphabeta T cell subsets. PMID- 26994219 TI - Multispectral Imaging of T and B Cells in Murine Spleen and Tumor. AB - Recent advances in multiplex immunohistochemistry techniques allow for quantitative, spatial identification of multiple immune parameters for enhanced diagnostic and prognostic insight. However, applying such techniques to murine fixed tissues, particularly sensitive epitopes, such as CD4, CD8alpha, and CD19, has been difficult. We compared different fixation protocols and Ag-retrieval techniques and validated the use of multiplex immunohistochemistry for detection of CD3(+)CD4(+) and CD3(+)CD8(+) T cell subsets in murine spleen and tumor. This allows for enumeration of these T cell subsets within immune environments, as well as the study of their spatial distribution. PMID- 26994220 TI - Relationship of NKG2C Copy Number with the Distribution of Distinct Cytomegalovirus-Induced Adaptive NK Cell Subsets. AB - CD94/NKG2C and lack of FcepsilonRgamma (FcRgamma) expression are considered markers of the adaptive NK cell response to human CMV (HCMV) infection. Despite the fact that FcRgamma(-) and NKG2C(bright) NK cells share some phenotypic, epigenetic, and functional features, their relationship remains unclear. To address this issue, a systematic analysis of NKG2C(bright) and FcRgamma expression was carried out in NK cells from a cohort of healthy young adults (n = 81) considering NKG2C copy number, previously related to the magnitude of NKG2C(+) NK cell expansion. NKG2C(bright) and FcRgamma(-) NK cells coincided in a subgroup of HCMV(+) individuals, pointing to a common host-virus interaction pattern. Even though FcRgamma loss was often confined to expanded NKG2C(bright) NK cells, both markers appeared occasionally dissociated, consistent with the existence of distinct adaptive NK cell subsets. Remarkably, FcRgamma loss was mostly accumulated within the NKG2C(bright) subset in NKG2C(+/+) subjects, whereas NKG2C(-)FcRgamma(-) NK cell subpopulations were more frequently detected in NKG2C(+/del) donors and also in NKG2C(del) (/del) individuals, independently of activating killer Ig-like receptor expression. The distribution of other NK receptors (i.e., killer Ig-like receptor, LILRB1, or CD57) supported a sequential differentiation from NKG2C(bright)FcRgamma(+) to NKG2C(bright)FcRgamma(-) NK cells. Noticeably, NKG2C(bright) NK cells produced more TNF-alpha in response to Ab-dependent activation, regardless of their FcRgamma levels. Moreover, the TNF alpha response of NKG2C(-)FcRgamma(-) subpopulations was lower than that of concurrent NKG2C(bright)FcRgamma(-) NK cells, further supporting that FcRgamma levels and enhanced potential for cytokine production are uncoupled. Overall, our data extend the characterization of adaptive NK cell subsets that differentiate in response to HCMV, supporting a relationship between their distribution and NKG2C copy number. PMID- 26994221 TI - Transient Surface CCR5 Expression by Naive CD8+ T Cells within Inflamed Lymph Nodes Is Dependent on High Endothelial Venule Interaction and Augments Th Cell Dependent Memory Response. AB - In inflamed lymph nodes, Ag-specific CD4(+) and CD8(+) T cells encounter Ag bearing dendritic cells and, together, this complex enhances the release of CCL3 and CCL4, which facilitate additional interaction with naive CD8(+) T cells. Although blocking CCL3 and CCL4 has no effect on primary CD8(+) T cell responses, it dramatically impairs the development of memory CD8(+) T cells upon Ag rechallenge. Despite the absence of detectable surface CCR5 expression on circulating native CD8(+) T cells, these data imply that naive CD8(+) T cells are capable of expressing surface CCR5 prior to cognate Ag-induced TCR signaling in inflamed lymph nodes; however, the molecular mechanisms have not been characterized to date. In this study, we show that CCR5, the receptor for CCL3 and CCL4, can be transiently upregulated on a subset of naive CD8(+) T cells and that this upregulation is dependent on direct contact with the high endothelial venule in inflamed lymph node. Binding of CD62L and CD11a on T cells to their ligands CD34 and CD54 on the high endothelial venule can be enhanced during inflammation. This enhanced binding and subsequent signaling promote the translocation of CCR5 molecules from intracellular vesicles to the surface of the CD8(+) T cell. The upregulation of CCR5 on the surface of the CD8(+) T cells increases the number of contacts with Ag-bearing dendritic cells, which ultimately results in increased CD8(+) T cell response to Ag rechallenge. PMID- 26994222 TI - Spring Viremia of Carp Virus N Protein Suppresses Fish IFNphi1 Production by Targeting the Mitochondrial Antiviral Signaling Protein. AB - For a virus to replicate efficiently, it must try and inhibit host IFN expression because IFN is an important host defense at early stages after viral infection. For aquatic viruses, the mechanisms used to escape the hosts IFN system are still unclear. In this study, we show that the N protein of spring viremia of carp virus (SVCV) inhibits zebrafish IFNphi1 production by degrading the mitochondrial antiviral signaling protein (MAVS). First, the upregulation of IFNphi1 promoter activity stimulated by polyinosinic:polycytidylic acid, retinoic acid-inducible gene I (RIG-I) or MAVS was suppressed by the SVCV infection. However, the upregulation by the downstream factor of the RIG-I-like receptor signaling pathway, TANK-binding kinase 1, was not affected. Notably, at the protein level, MAVS decreased remarkably when cells were infected with SVCV. Second, consistent with the result of the SVCV infection, overexpression of the N protein of SVCV blocked the IFNphi1 transcription activated by MAVS and downregulated MAVS expression at the protein level but not at the mRNA level. Further analysis demonstrated that the N protein targeted MAVS for K48-linked ubiquitination, which promoted the degradation of MAVS. These data indicated that fish MAVS could be degraded by the N protein of SVCV through the ubiquitin-proteasome pathway. To our knowledge, this is the first article of a fish RIG-I-like receptor pathway interfered by an aquatic virus in an ubiquitin-proteasome manner, suggesting that immune evasion of a virus also exists in lower vertebrates. PMID- 26994223 TI - A MicroRNA-Mediated Positive Feedback Regulatory Loop of the NF-kappaB Pathway in Litopenaeus vannamei. AB - In the evolutionarily conserved canonical NF-kappaB pathway, degradation of the NF-kappaB inhibitor IkappaB in the cytoplasmic NF-kappaB/IkappaB complex allows the liberated NF-kappaB to translocate into the nucleus to activate various target genes. The regulatory mechanism governing this process needs further investigation. In this study, a novel microRNA, temporarily named miR-1959, was first identified from an invertebrate Litopenaeus vannamei miR-1959 targets the 3'-untranslated region of the IkappaB homolog Cactus gene and reduces the protein level of Cactus in vivo, whereas the NF-kappaB homolog Dorsal directly binds the miR-1959 promoter to activate its transcription. Therefore, miR-1959 mediates a positive feedback regulatory loop, in that Dorsal activates miR-1959 expression, and in turn, miR-1959 inhibits the expression of Cactus, further leading to enhanced activation of Dorsal. Moreover, miR-1959 regulates the expression of many antimicrobial peptides in vivo and is involved in antibacterial immunity. To our knowledge, it is the first discovery of a microRNA-mediated feedback loop that directly regulates the NF-kappaB/IkappaB complex. This positive feedback loop could collaborate with the known NF-kappaB/IkappaB negative loop to generate a dynamic balance to regulate the activity of NF-kappaB, thus constituting an effective regulatory mechanism at the critical node of the NF-kappaB pathway. PMID- 26994224 TI - Alastair A Spence C.B.E. 1936-2015. PMID- 26994225 TI - Perioperative management of diabetes and the emerging role of anaesthetists as perioperative physicians. PMID- 26994226 TI - How can we prevent opioid induced hyperalgesia in surgical patients? PMID- 26994227 TI - Ketamine and propofol sedation by emergency medicine specialists: mainstream or menace? PMID- 26994228 TI - Towards individualized perioperative, goal-directed haemodynamic algorithms for patients of advanced age: observations during a randomized controlled trial (NCT01141894). AB - BACKGROUND: During a previous study on intraoperative goal-directed haemodynamic treatment (GDHT) in elderly patients, cardiac performance did not improve as anticipated (ClinicalTrials.gov NCT01141894). We hypothesized that in this group, responsiveness to interventions could be predicted by individual patient characteristics. METHODS: Data for the present study were collected during a previously performed, single-centre, open, randomized, and controlled parallel group superiority trial in patients aged >=70 yr undergoing hip-fracture surgery. Haemodynamic parameters were collected by the LiDCOplusTM monitor. The GDHT group received oxygen delivery-guided fluid challenges and dobutamine infusion. Management in the routine fluid treatment group was clinician guided without access to LiDCOplusTM readings. In the GDHT group, independent predictors were assessed by multiple logistic regression analyses of two outcomes: first fluid challenge response (defined as increase of stroke volume by >=10%); and overall intervention response (maintenance of oxygen delivery at the end of surgery). RESULTS: Data from 72 routine fluid treatment and 70 GDHT patients were analysed. Clinician-guided pre-anaesthesia fluid loading increased the stroke volume in 14% of patients, and 17% of patients increased or maintained oxygen delivery at the end of surgery. The GDHT-guided first and subsequent fluid challenges were associated with increased stroke volume in 39 and 9% of patients, respectively, and increased or maintained oxygen delivery was present in 47% of patients at the end of surgery. In the GDHT group, a baseline stroke volume index (<28 ml m(-2)) was an independent predictor of first fluid challenge response, and a baseline oxygen delivery index (<330 ml min(-1) m(-2)) was a predictor of maintained or increased oxygen delivery. CONCLUSIONS: Fewer patients responded to GDHT than anticipated. Our data suggest that individual characteristics could predict the haemodynamic responses. CLINICAL TRIAL REGISTRATION: NCT01141894. PMID- 26994229 TI - Ultrasound assessment of gastric volume in children after drinking carbohydrate containing fluids. AB - BACKGROUND: Gastric ultrasound is a valid tool for non-invasive assessment of the nature and volume of gastric contents in adults and children. Perioperative fasting guidelines recommend oral carbohydrates up to 2 h before elective surgery. We evaluated gastric volume in children using ultrasound before and after drinking carbohydrate fluids before surgery. METHODS: Paediatric patients younger than 18 yr old undergoing elective surgery were enrolled. Initial ultrasound assessment of gastric volume was performed after fasting for 8 h. Two hours before surgery, patients were given carbohydrate drinks: 15 ml kg(-1) for patients younger than 3 yr old and 10 ml kg(-1) for those more than 3 yr old. Before induction of general anaesthesia, the gastric volume was reassessed. Parental satisfaction scores (0=totally satisfied, 10=totally dissatisfied) and complications were recorded. RESULTS: Of the 86 enrolled patients, 79 completed the study; three refused to ingest the requested volume, and surgery was delayed for more than 2 h in four patients. The mean (sd) of the initial and second ultrasound measurements were 2.09 (0.97) and 1.85 (0.94) cm(2), respectively (P=0.01; mean difference 0.24 cm(2), 95% confidence interval 0.06-0.43). The median (interquartile range) satisfaction score was 2.4 (0-6). Two instances of postoperative vomiting and one instance of postoperative nausea occurred. CONCLUSIONS: Carbohydrate fluids ingested 2 h before surgery reduced the gastric volume and did not cause serious complications in paediatric patients. Parents were satisfied with the preoperative carbohydrate drink. Children may benefit from drinking carbohydrate fluids up to 2 h before elective surgery. CLINICAL TRIAL REGISTRATION: cris.nih.go.kr (KCT0001546). PMID- 26994230 TI - Extrafascial injection for interscalene brachial plexus block reduces respiratory complications compared with a conventional intrafascial injection: a randomized, controlled, double-blind trial. AB - BACKGROUND: Hemidiaphragmatic paresis after ultrasound-guided interscalene brachial plexus block is reported to occur in up to 100% of patients. We tested the hypothesis that an injection lateral to the brachial plexus sheath reduces the incidence of hemidiaphragmatic paresis compared with a conventional intrafascial injection, while providing similar analgesia. METHODS: Forty ASA I III patients undergoing elective shoulder and clavicle surgery under general anaesthesia were randomized to receive an ultrasound-guided interscalene brachial plexus block for analgesia, using 20 ml bupivacaine 0.5% with epinephrine 1:200 000 injected either between C5 and C6 within the interscalene groove (conventional intrafascial injection), or 4 mm lateral to the brachial plexus sheath (extrafascial injection). The primary outcome was incidence of hemidiaphragmatic paresis (diaphragmatic excursion reduction >75%), measured by M mode ultrasonography, before and 30 min after the procedure. Secondary outcomes were forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow. Additional outcomes included time to first opioid request and pain scores at 24 h postoperatively (numeric rating scale, 0-10). RESULTS: The incidences of hemidiaphragmatic paresis were 90% (95% CI: 68-99%) and 21% (95% CI: 6-46%) in the conventional and extrafascial injection groups, respectively (P<0.0001). Other respiratory outcomes were significantly better preserved in the extrafascial injection group. The mean time to first opioid request was similar between groups (conventional: 802 min [95% CI: 620-984 min]; extrafascial: 973 min [95% CI: 791-1155 min]; P=0.19) as were pain scores at 24 h postoperatively (conventional: 1.6 [95% CI: 0.9-2.2]; extrafascial: 1.6 [95% CI: 0.8-2.4]; P=0.97). CONCLUSIONS: Ultrasound-guided interscalene brachial plexus block with an extrafascial injection reduces the incidence of hemidiaphragmatic paresis and impact on respiratory function while providing similar analgesia, when compared with a conventional injection. CLINICAL TRIAL REGISTRATION: NCT02074397. PMID- 26994231 TI - Diabetic neuropathy increases stimulation threshold during popliteal sciatic nerve block. AB - BACKGROUND: Peripheral nerve stimulation is commonly used for nerve localization in regional anaesthesia, but recommended stimulation currents of 0.3-0.5 mA do not reliably produce motor activity in the absence of intraneural needle placement. As this may be particularly true in patients with diabetic neuropathy, we examined the stimulation threshold in patients with and without diabetes. METHODS: Preoperative evaluation included a neurological exam and electroneurography. During ultrasound-guided popliteal sciatic nerve block, we measured the current required to produce motor activity for the tibial and common peroneal nerve in diabetic and non-diabetic patients. Proximity to the nerve was evaluated post-hoc using ultrasound imaging. RESULTS: Average stimulation currents did not differ between diabetic (n=55) and non-diabetic patients (n=52). Although the planned number of patients was not reached, the power goal for the mean stimulation current was met. Subjects with diminished pressure perception showed increased thresholds for the common peroneal nerve (median 1.30 vs. 0.57 mA in subjects with normal perception, P=0.042), as did subjects with decreased pain sensation (1.60 vs. 0.50 mA in subjects with normal sensation, P=0.038). Slowed ulnar nerve conduction velocity predicted elevated mean stimulation current (r=-0.35, P=0.002). Finally, 15 diabetic patients required more than 0.5 mA to evoke a motor response, despite intraneural needle placement (n=4), or required currents >=2 mA despite needle-nerve contact, vs three such patients (1 intraneural, 2 with >=2 mA) among non-diabetic patients (P=0.003). CONCLUSIONS: These findings suggest that stimulation thresholds of 0.3-0.5 mA may not reliably determine close needle-nerve contact during popliteal sciatic nerve block, particularly in patients with diabetic neuropathy. CLINICAL TRIAL REGISTRATION: NCT01488474. PMID- 26994232 TI - Tunnelling of thoracic epidural catheters is associated with fewer catheter related infections: a retrospective registry analysis. AB - BACKGROUND: Catheter-related infections are a serious complication of continuous thoracic epidural analgesia. Tunnelling catheters subcutaneously may reduce infection risk. We thus tested the hypothesis that tunnelling of thoracic epidural catheters is associated with a lower risk of catheter-related infections. METHODS: Twenty-two thousand, four hundred and eleven surgical patients with continuous thoracic epidural analgesia included in the German Network for Regional Anaesthesia registry between 2007 and 2014 were grouped by whether their catheters were tunnelled (n=12 870) or not (n=9541). Catheter related infections in each group were compared with Student's unpaired t and chi(2) tests. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with logistic regression, adjusting for potential confounding factors, including age, ASA physical status score, use of catheter for >=4 days, multiple skin puncture, hospital, and surgical department. RESULTS: There were fewer catheter-related infections in patients with tunnelled catheters (4.5 vs 5.5%, P<0.001). Mild infections were also less common (4.0 vs 4.6%, P=0.009), as were moderate infections (0.4 vs 0.8%, P<0.001). After adjustment for potential confounding factors, tunnelling remained an independent prevention for any grade of infection (adjusted OR 0.51, 95% CI 0.42-0.61, P<0.001) and for mild infections (adjusted OR 0.54, 95% CI 0.43-0.66, P<0.001) and moderate and severe infections (adjusted OR 0.44, 95% CI 0.28-0.70, P=0.001). CONCLUSION: Tunnelling was associated with a lower risk of thoracic epidural catheter-related infections. PMID- 26994233 TI - In search for in vivo methods to visualize clot forming in cut vessels and interrupted flow. PMID- 26994234 TI - Pocket-sized transthoracic echocardiography for intraoperative monitoring of heart function in spontaneously breathing patients and the optimal acoustic window. PMID- 26994235 TI - Difficult tracheal intubation in bariatric surgery patients, a myth or reality? PMID- 26994236 TI - Was Button gassed? PMID- 26994237 TI - GlideScope video laryngoscope-assisted nasotracheal intubation by cuff-inflation technique in head and neck cancer patients. PMID- 26994238 TI - Variability of fasting outcomes observed in a single patient. PMID- 26994239 TI - Anaesthetic mask hooks: their economic and environmental costs. PMID- 26994240 TI - Anaesthesia for paediatric emergency surgery: an Italian survey of current clinical practice. PMID- 26994241 TI - Haemodynamic and cerebral oxygenation during paediatric laparoscopy in fluid optimized patients. PMID- 26994242 TI - Identification of variants of the ryanodine receptor type 1 in patients with exertional heat stroke and positive response to the malignant hyperthermia in vitro contracture test. PMID- 26994243 TI - Surface marking technique to locate needle insertion point for ultrasound-guided neuraxial block. PMID- 26994250 TI - Possible Interaction of Anti-PD-1 Therapy with the Effects of Radiosurgery on Brain Metastases. AB - Delayed radiation-induced vasculitic leukoencephalopathy related to stereotactic radiosurgery (SRS) of brain metastases has been reported to manifest clinically 9 to 18 months after treatment. Immune-modulating therapies have been introduced to treatment regimens for malignancies with metastatic predilection to the brain. The interaction of these systemic therapies with other modalities of treatment for brain metastases, namely, SRS, has not been fully characterized. We report two patients with metastatic malignancies to the brain who received SRS followed by immunotherapy with monoclonal antibodies (mAb) to programmed death 1 (PD-1). Both patients appeared to have early clinical and radiologic progression of their treated lesions, which was highly suspicious for tumor progression. Both patients underwent surgical resection of their lesions and the material was submitted for histopathologic examination. Pathologic examination in both cases showed predominantly radiation-induced changes characterized by reactive astrocytosis and vascular wall infiltration by T lymphocytes. The accelerated response to SRS in these two patients was temporally related to the initiation of immunotherapy. We propose a possible biologic interaction between SRS and the PD-1 mAbs. Additionally, awareness of this potential occurrence is critical for accurate interpretation and proper management of clinical and radiologic findings in these patients. Cancer Immunol Res; 4(6); 481-7. (c)2016 AACR. PMID- 26994257 TI - The World Report on Ageing and Health. PMID- 26994258 TI - Investing in Health to Create a Third Demographic Dividend. AB - The world is aging as a result of unprecedented successes worldwide adding 30 years of life expectancy and presenting great opportunities for all of society, but only if we invest effectively. This article, written as a requested background article for the World Health Organization 2015 World Report on Aging, proposes that creating health into the oldest ages could lay the basis for a third demographic dividend resulting from the societal benefits from the generative social capital of older adults, on top of the second demographic dividend's savings associated with longer lives. The combination would contribute to stronger and wealthier societies, greater success of the young, and increased societal ability to provide the humane supports needed at the end of life, plus a dividend that would endure. We now know that prevention works at every age and into the oldest ages. A life-course approach to prevention and health promotion is the key investment. The creation of geriatrically knowledgeable and integrated public health, medical and social care systems has the potential to amplify capabilities and well-being to the end of life. Healthy older populations bring both desire for engagement and unique talents. Institutions designed to create impactful roles for older adults to contribute to the success of the young can activate the societal benefits and further enhance health at older ages. Creating a new vision for the opportunities of an older age is the first critical step toward experiencing the benefits of our longer lives and creating a sustained third demographic dividend. PMID- 26994259 TI - Healthy Ageing: Raising Awareness of Inequalities, Determinants, and What Could Be Done to Improve Health Equity. AB - PURPOSE OF THE STUDY: Social and scientific discourses on healthy ageing and on health equity are increasingly available, yet from a global perspective limited conceptual and analytical work connecting both has been published. This review was done to inform the WHO World Report on Ageing and Health and to inform and encourage further work addressing both healthy aging and equity. DESIGN AND METHODS: We conducted an extensive literature review on the overlap between both topics, privileging publications from 2005 onward, from low-, middle-, and high income countries. We also reviewed evidence generated around the WHO Commission on Social Determinants of Health, applicable to ageing and health across the life course. RESULTS: Based on data from 194 countries, we highlight differences in older adults' health and consider three issues: First, multilevel factors that contribute to differences in healthy ageing, across contexts; second, policies or potential entry points for action that could serve to reduce unfair differences (health inequities); and third, new research areas to address the cause of persistent inequities and gaps in evidence on what can be done to increase healthy ageing and health equity. IMPLICATIONS: Each of these areas warrant in depth analysis and synthesis, whereas this article presents an overview for further consideration and action. PMID- 26994260 TI - Elder Abuse: Global Situation, Risk Factors, and Prevention Strategies. AB - PURPOSE: Elder mistreatment is now recognized internationally as a pervasive and growing problem, urgently requiring the attention of health care systems, social welfare agencies, policymakers, and the general public. In this article, we provide an overview of global issues in the field of elder abuse, with a focus on prevention. DESIGN AND METHODS: This article provides a scoping review of key issues in the field from an international perspective. RESULTS: By drawing primarily on population-based studies, this scoping review provided a more valid and reliable synthesis of current knowledge about prevalence and risk factors than has been available. Despite the lack of scientifically rigorous intervention research on elder abuse, the review also identified 5 promising strategies for prevention. IMPLICATIONS: The findings highlight a growing consensus across studies regarding the extent and causes of elder mistreatment, as well as the urgent need for efforts to make elder mistreatment prevention programs more effective and evidence based. PMID- 26994261 TI - The Right to Health of Older People. AB - A focus on the right to the enjoyment of the highest attainable standard of health (hereinafter, "the right to health") draws attention to the health needs of older people, including the most marginalized among them. Many factors that influence vulnerability or impede the enjoyment of health and access to quality services result from an inability to freely exercise these human rights. A human rights approach can help to address the legal, social, and structural barriers to good health for older persons, clarifying the legal obligations of State and non State actors to uphold and respect these rights. However, despite growing impetus for action, this area has historically received limited attention. Drawing on practice examples from different regions, this article unpacks the meaning of the right to health and other related human rights of older people in practice, covering both health care and underlying determinants of their health. Questions of availability, accessibility, acceptability, and quality are highlighted from the perspective of older people's health and well-being. The article brings together knowledge, principles, norms, and standards from the human rights law, health, and ageing arenas. By making links between these arenas, it is hoped that the article fills a gap in thinking on how to achieve the progressive realization of the right to health of older people and the effective promotion and protection of their other related human rights, which are crucial for the enjoyment of health. PMID- 26994262 TI - Genetic Influences on Functional Capacities in Aging. AB - PURPOSE: Older populations are characterized by great heterogeneity in functional capacities and understanding the factors underlying these differences has been a major area of research for some decades. Genetic differences arguably play an important role in the heterogeneity observed for many outcomes among older individuals. However, the role of genes in the variation and trajectories of functional capacities in older age is poorly understood. This review was conducted to explore the evidence for genetic influences on physical functional capacities in aging. DESIGN AND METHODS: This rapid review was conducted using the following criteria: journal articles retrieved from the PubMed, Embase, AgeLine, Scopus, and Web of Science electronic databases including the key words: genetics, genotype, polymorphism, physical or functional performance, functional capacity, activities of daily living, older, and elderly. In total, 118 articles were included for initial review. RESULTS: The heritability of objective measures of physical function ranges from 30% to 60% in studies of older twins. There is a paucity of evidence about genetic influences on functional capacities, but some candidate genes related to functional capacity have been identified. IMPLICATIONS: No strong candidate genes exist for functional capacities. Current methodologies are beginning to generate new evidence about genetic influences on overall physical function at older ages, but the variety of measures of functional capacity makes evidence difficult to compare. PMID- 26994263 TI - Age-Associated Skin Conditions and Diseases: Current Perspectives and Future Options. AB - The International League of Dermatological Societies (ILDS), a global, not-for profit organization representing 157 dermatological societies worldwide, has identified the consequences of skin aging as one of the most important grand challenges in global skin health. Reduced functional capacity and increased susceptibility of the skin with development of dermatoses such as dry skin, itching, ulcers, dyspigmentation, wrinkles, fungal infections, as well as benign and malignant tumors are the most common skin conditions in aged populations worldwide. Environmental (e.g., pollution) and lifestyle factors (e.g., smoking, sunbed use) negatively affect skin health. In turn altered appearance, dry skin, chronic wounds, and other conditions decrease general health and reduce the likelihood for healthy and active aging. Preventive skin care includes primary, secondary, and tertiary interventions. Continuous sun protection from early childhood onward is most important, to avoid extrinsic skin damage and skin cancer. Exposure to irritants, allergens, or other molecules damaging the skin must be avoided or reduced to a minimum. Public health approaches are needed to implement preventive and basic skin care worldwide to reach high numbers of dermatological patients and care receivers. Education of primary caregivers and implementation of community dermatology are successful strategies in resource poor countries. Besides specialist physicians, nurses and other health care professionals play important roles in preventing and managing age-related skin conditions in developing as well as in developed countries. Healthy skin across the life course leads to better mental and emotional health, positive impact on social engagement, and healthier, more active, and productive lives. PMID- 26994264 TI - Musculoskeletal Health Conditions Represent a Global Threat to Healthy Aging: A Report for the 2015 World Health Organization World Report on Ageing and Health. AB - Persistent pain, impaired mobility and function, and reduced quality of life and mental well-being are the most common experiences associated with musculoskeletal conditions, of which there are more than 150 types. The prevalence and impact of musculoskeletal conditions increase with aging. A profound burden of musculoskeletal disease exists in developed and developing nations. Notably, this burden far exceeds service capacity. Population growth, aging, and sedentary lifestyles, particularly in developing countries, will create a crisis for population health that requires a multisystem response with musculoskeletal health services as a critical component. Globally, there is an emphasis on maintaining an active lifestyle to reduce the impacts of obesity, cardiovascular conditions, cancer, osteoporosis, and diabetes in older people. Painful musculoskeletal conditions, however, profoundly limit the ability of people to make these lifestyle changes. A strong relationship exists between painful musculoskeletal conditions and a reduced capacity to engage in physical activity resulting in functional decline, frailty, reduced well-being, and loss of independence. Multilevel strategies and approaches to care that adopt a whole person approach are needed to address the impact of impaired musculoskeletal health and its sequelae. Effective strategies are available to address the impact of musculoskeletal conditions; some are of low cost (e.g., primary care-based interventions) but others are expensive and, as such, are usually only feasible for developed nations. In developing nations, it is crucial that any reform or development initiatives, including research, must adhere to the principles of development effectiveness to avoid doing harm to the health systems in these settings. PMID- 26994265 TI - Aging and Hearing Health: The Life-course Approach. AB - Sensory abilities decline with age. More than 5% of the world's population, approximately 360 million people, have disabling hearing loss. In adults, disabling hearing loss is defined by thresholds greater than 40 dBHL in the better hearing ear.Hearing disability is an important issue in geriatric medicine because it is associated with numerous health issues, including accelerated cognitive decline, depression, increased risk of dementia, poorer balance, falls, hospitalizations, and early mortality. There are also social implications, such as reduced communication function, social isolation, loss of autonomy, impaired driving ability, and financial decline. Furthermore, the onset of hearing loss is gradual and subtle, first affecting the detection of high-pitched sounds and with difficulty understanding speech in noisy but not in quiet environments. Consequently, delays in recognizing and seeking help for hearing difficulties are common. Age-related hearing loss has no known cure, and technologies (hearing aids, cochlear implants, and assistive devices) improve thresholds but do not restore hearing to normal. Therefore, health care for persons with hearing loss and people within their communication circles requires education and counseling (e.g., increasing knowledge, changing attitudes, and reducing stigma), behavior change (e.g., adapting communication strategies), and environmental modifications (e.g., reducing noise). In this article, we consider the causes, consequences, and magnitude of hearing loss from a life-course perspective. We examine the concept of "hearing health," how to achieve it, and implications for policy and practice. PMID- 26994266 TI - Updating the Evidence for Physical Activity: Summative Reviews of the Epidemiological Evidence, Prevalence, and Interventions to Promote "Active Aging". AB - PURPOSE OF THE STUDY: There is a global imperative to increase awareness of the emerging evidence on physical activity (PA) among older adults. "Healthy aging" has traditionally focused on preventing chronic disease, but greater efforts are required to reduce frailty and dependency and to maintain independent physical and cognitive function and mental health and well-being. DESIGN AND METHODS: This integrated review updates the epidemiological data on PA, summarizes the existing evidence-based PA guidelines, describes the global magnitude of inactivity, and finally describes the rationale for action. The first section updates the epidemiological evidence for reduced cardiometabolic risk, reduced risks of falls, the burgeoning new evidence on improved cognitive function and functional capacity, and reduced risk of depression, anxiety, and dementia. This is followed by a summary of population prevalence studies among older adults. Finally, we present a "review of reviews" of PA interventions delivered from community or population settings, followed by a consideration of interventions among the "oldest-old," where efforts are needed to increase resistance (strength) training and balance. RESULTS: This review identifies the global importance of considering "active aging" beyond the established benefits attributed to noncommunicable disease prevention alone. IMPLICATIONS: Innovative population-level efforts are required to address physical inactivity, prevent loss of muscle strength, and maintain balance in older adults. Specific investment in healthy aging requires global policy support from the World Health Organization and is implemented at the national and regional levels, in order to reduce the burden of disease and disability among older adults. PMID- 26994267 TI - A Global View on the Effects of Work on Health in Later Life. AB - PURPOSE OF THE STUDY: Work is an important environment shaping the aging processes during the adult years. Therefore, the cumulative and acute effects of work characteristics on late-life health deserve great attention. Given that population aging has become a global trend with ensuing changes in labor markets around the world, increased attention is paid to investigating the effects of the timing of retirement around the world and the macroeconomic benefits often associated with delaying retirement. It will be essential for societies with aging populations to maintain productivity given an aging workforce and for individuals it will be crucial to add healthy and meaningful years rather than just years to their lives. DESIGN AND METHODS: We first describe the available evidence about participation of older workers (65+) in the labor force in high, middle, and low-income countries. Second, we discuss the individual-level and societal influences that might govern labor-force participation of older adults. Thirdly, we review evidence on the association between work on the one and physical, mental, and cognitive health in later life on the other. RESULTS AND IMPLICATIONS: Globally, both is true: work supports healthy aging and jeopordizes it. We draw implications for policymaking in terms of social protection, HR policies, and older employee employability. PMID- 26994268 TI - Medical and Assistive Health Technology: Meeting the Needs of Aging Populations. AB - PURPOSE OF THE STUDY: To identify policy gaps in the delivery and availability of assistive health technology (AHT) and medical devices (MD) for aging populations, particularly in low- and middle-income countries (LMICs). DESIGN AND METHODS: The findings presented in this paper are the results of several narrative overviews. They provide a contextual analysis of the conclusions and evidence from WHO commissioned research and expert consultations in 2013 and 2014, as well as a synthesis of literature reviews conducted on AHT and MD. RESULTS: Practical, life enhancing support for older people through AHT, MD, and related health and social services is a neglected issue. This is particularly so in LMICs where the biggest increases in aging populations are occurring, and yet where there is commonly little or no access to these vital components of healthy aging. IMPLICATIONS: Health technologies, especially medical and assistive health technology, are essential to ensure older people's dignity and autonomy, but their current and potential benefits have received little recognition in LMICs. Viewing these technologies as relevant only to disabled people is an inadequate approach. They should be accessible to both older adults with disabilities and older adults with functional limitation. Many countries need much greater official awareness of older adults' needs and preferences. Such attitudinal changes should then be reflected in laws and regulations to address the specificities of care for older people. PMID- 26994269 TI - Transitions to retirement. PMID- 26994270 TI - Graceful ageing for the career psychiatrist. PMID- 26994271 TI - Transition to retirement. PMID- 26994274 TI - Back-to-base pulse oximetry to prevent inpatient suicide. PMID- 26994275 TI - The need for a Quality in Australian Mental Health Care study. PMID- 26994276 TI - MacDonaldisation of the Medicare schedule. PMID- 26994277 TI - Vortioxetine in bipolar depression induces a mixed/manic switch. PMID- 26994287 TI - The SEB-1 Transcription Factor Binds to the STRE Motif in Neurospora crassa and Regulates a Variety of Cellular Processes Including the Stress Response and Reserve Carbohydrate Metabolism. AB - When exposed to stress conditions, all cells induce mechanisms resulting in an attempt to adapt to stress that involve proteins which, once activated, trigger cell responses by modulating specific signaling pathways. In this work, using a combination of pulldown assays and mass spectrometry analyses, we identified the Neurospora crassa SEB-1 transcription factor that binds to the Stress Response Element (STRE) under heat stress. Orthologs of SEB-1 have been functionally characterized in a few filamentous fungi as being involved in stress responses; however, the molecular mechanisms mediated by this transcription factor may not be conserved. Here, we provide evidences for the involvement of N. crassa SEB-1 in multiple cellular processes, including response to heat, as well as osmotic and oxidative stress. The Deltaseb-1 strain displayed reduced growth under these conditions, and genes encoding stress-responsive proteins were differentially regulated in the Deltaseb-1 strain grown under the same conditions. In addition, the SEB-1-GFP protein translocated from the cytosol to the nucleus under heat, osmotic, and oxidative stress conditions. SEB-1 also regulates the metabolism of the reserve carbohydrates glycogen and trehalose under heat stress, suggesting an interconnection between metabolism control and this environmental condition. We demonstrated that SEB-1 binds in vivo to the promoters of genes encoding glycogen metabolism enzymes and regulates their expression. A genome-wide transcriptional profile of the Deltaseb-1 strain under heat stress was determined by RNA-seq, and a broad range of cellular processes was identified that suggests a role for SEB-1 as a protein interconnecting these mechanisms. PMID- 26994288 TI - The Sorghum Gene for Leaf Color Changes upon Wounding (P) Encodes a Flavanone 4 Reductase in the 3-Deoxyanthocyanidin Biosynthesis Pathway. AB - Upon wounding or pathogen invasion, leaves of sorghum [Sorghum bicolor (L.) Moench] plants with the P gene turn purple, whereas leaves with the recessive allele turn brown or tan. This purple phenotype is determined by the production of two 3-deoxyanthocyanidins, apigeninidin and luteolinidin, which are not produced by the tan-phenotype plants. Using map-based cloning in progeny from a cross between purple Nakei-MS3B (PP) and tan Greenleaf (pp) cultivars, we isolated this gene, which was located in a 27-kb genomic region around the 58.1 Mb position on chromosome 6. Four candidate genes identified in this region were similar to the maize leucoanthocyanidin reductase gene. None of them was expressed before wounding, and only the Sb06g029550 gene was induced in both cultivars after wounding. The Sb06g029550 protein was detected in Nakei-MS3B, but only slightly in Greenleaf, in which it may be unstable because of a Cys252Tyr substitution. A recombinant Sb06g029550 protein had a specific flavanone 4 reductase activity, and converted flavanones (naringenin or eriodictyol) to flavan-4-ols (apiforol or luteoforol) in vitro Our data indicate that the Sb06g029550 gene is involved in the 3-deoxyanthocyanidin synthesis pathway. PMID- 26994289 TI - Organ Length Control by an ADAMTS Extracellular Protease in Caenorhabditis elegans. AB - MIG-17, a secreted protease of the ADAMTS family, acts in the directed migration of gonadal distal tip cells (DTCs) through regulation of the gonadal basement membrane in Caenorhabditis elegans Here, we show that MIG-17 is also required for the control of pharynx elongation during animal growth. We found that the pharynx was elongated in mig-17 mutants compared with wild type. MIG-17 localized to the pharyngeal basement membrane as well as to the gonadal basement membrane. The number of nuclei in the pharynx, and the pumping rate of the pharynx, were not affected in mig-17 mutants, suggesting that cells constituting the pharynx are elongated, although the pharynx functions normally in these mutants. In contrast to the control of DTC migration, MIG-18, a secreted cofactor of MIG-17, was not essential for pharynx length regulation. In addition, the downstream pathways of MIG-17 involving LET-2/type IV collagen, FBL-1/fibulin-1, and NID-1/nidogen, partly diverged from those in gonad development. These results indicate that basement membrane remodeling is important for organ length regulation, and suggest that MIG-17/ADAMTS functions in similar but distinct molecular machineries in pharyngeal and gonadal basement membranes. PMID- 26994290 TI - Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females. AB - Meiotic recombination is a genetic process that is critical for proper chromosome segregation in many organisms. Despite being fundamental for organismal fitness, rates of crossing over vary greatly between taxa. Both genetic and environmental factors contribute to phenotypic variation in crossover frequency, as do genotype environment interactions. Here, we test the hypothesis that maternal age influences rates of crossing over in a genotypic-specific manner. Using classical genetic techniques, we estimated rates of crossing over for individual Drosophila melanogaster females from five strains over their lifetime from a single mating event. We find that both age and genetic background significantly contribute to observed variation in recombination frequency, as do genotype-age interactions. We further find differences in the effect of age on recombination frequency in the two genomic regions surveyed. Our results highlight the complexity of recombination rate variation and reveal a new role of genotype by maternal age interactions in mediating recombination rate. PMID- 26994291 TI - A High-Density SNP Genetic Linkage Map and QTL Analysis of Growth-Related Traits in a Hybrid Family of Oysters (Crassostrea gigas * Crassostrea angulata) Using Genotyping-by-Sequencing. AB - Oysters are among the most important species in global aquaculture. Crassostrea gigas, and its subspecies C. angulata, are the major cultured species. To determine the genetic basis of growth-related traits in oysters, we constructed a second-generation linkage map from 3367 single-nucleotide polymorphisms (SNPs) based on genotyping-by-sequencing, genotyped from a C. gigas * C. angulata hybrid family. These 3367 SNPs were distributed on 1695 markers, which were assigned to 10 linkage groups. The genetic linkage map had a total length of 1084.3 cM, with an average of 0.8 cM between markers; it thus represents the densest genetic map constructed for oysters to date. Twenty-seven quantitative trait loci (QTL) for five growth-related traits were detected. These QTL could explain 4.2-7.7% (mean = 5.4%) of the phenotypic variation. In total, 50.8% of phenotypic variance for shell width, 7.7% for mass weight, and 34.1% for soft tissue weight were explained. The detected QTL were distributed among eight linkage groups, and more than half (16) were concentrated within narrow regions in their respective linkage groups. Thirty-eight annotated genes were identified within the QTL regions, two of which are key genes for carbohydrate metabolism. Other genes were found to participate in assembly and regulation of the actin cytoskeleton, signal transduction, and regulation of cell differentiation and development. The newly developed high-density genetic map, and the QTL and candidate genes identified provide a valuable genetic resource and a basis for marker-assisted selection for C. gigas and C. angulata. PMID- 26994292 TI - Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster. AB - About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions. PMID- 26994293 TI - Pro: Buttonhole cannulation of arteriovenous fistulae. AB - Arteriovenous fistulae remain the access of choice for most hemodialysis patients. However, several factors limit their uptake and long-term patency, resulting in suboptimal prevalent rates in many high-income countries. Patients place considerable value on the avoidance of vascular access complications, pain and disfigurement. The approach to cannulation is a modifiable practice that could improve patient-important outcomes, with buttonhole needling offering some theoretical advantages over the standard rope-ladder and area methods. In this narrative review, we summarize key findings of studies reporting the benefits and risks associated with the buttonhole method, highlighting methodological limitations as well as recent refinements to the technique that may represent potential opportunities for reducing infection risk. We highlight the need for greater certainty surrounding the potential benefits of the buttonhole cannulation technique and propose some directions for future research. PMID- 26994294 TI - Moderator's View: Buttonhole cannulation of arteriovenous fistulae: great caution is warranted. AB - Potential advantages of buttonhole (BH) cannulation over the standard rope-ladder technique have been claimed on the basis of small sized, potentially biased observational studies with a relatively short follow-up. On the contrary, randomized controlled trials (RCTs) show inconclusive or conflicting results. The uncertain benefit must thus be weighed against a definite increase in the infectious risk with the BH technique, which may not be completely abolished by preventative strategies. Awaiting the results of long-term studies (>2-3 years follow-up), the widespread use of the BH technique is not warranted, especially in busy in-centre haemodialysis (HD) settings with many rotating nurses. In our experience, the BH technique has been implemented safely in a self-care HD unit, presumably because of the limited number of cannulators and, in the case of self cannulating patients, direct supervision by a small team of nurses. Units (and patients) willing to use the BH technique should be aware that BH is an extremely demanding technique and requires constant and strict adherence to the protocol. Regular monitoring of infection rates is recommended. Additional RCTs are clearly warranted, together with large-sized observational studies with multivariable adjustment. PMID- 26994295 TI - Con: Buttonhole cannulation of arteriovenous fistulae. AB - Successful cannulation of arteriovenous fistulas (AVFs) using a safe and effective technique that minimizes patient harm is a crucial aspect of haemodialysis treatment. Although the current standard of care for many years has been the rope-ladder technique (using sharp needles to cannulate rotating sites across the entire AVF), a number of enthusiasts have recently advocated for the alternative method of buttonhole cannulation (using blunt needles to repeatedly cannulate the same site via a healed track) on the basis of putative, as yet unproven benefits. In this article, we review all available observational studies, randomized controlled trials, and systematic reviews and meta-analyses that have compared the clinical outcomes of buttonhole and rope-ladder cannulation of AVFs. These studies clearly and consistently demonstrated that buttonhole cannulation causes significant and serious infectious harm to haemodialysis patients, especially in the home setting. No strategies or treatments have been proven to effectively mitigate this hazard of buttonhole cannulation. Moreover, buttonhole cannulation is associated with a higher rate of abandonment and has not been shown to have any proven benefit compared with the rope-ladder method. Specifically, buttonhole cannulation has not been shown to reduce cannulation-related pain, improve vascular access survival, reduce vascular access interventions, reduce haematoma formation, improve haemostasis or reduce aneurysm formation. Consequently, rope-ladder cannulation should remain the standard of care and buttonhole cannulation should only be used in rare circumstances (e.g. short segment AVFs where the only alternative is a haemodialysis catheter). PMID- 26994296 TI - The Utilization of Antithrombotic Therapy in Older Australians With Atrial Fibrillation. AB - WHAT IS KNOWN AND OBJECTIVE: Oral anticoagulants are essential drugs for the prevention of thromboembolic events in patients with atrial fibrillation (AF). Anticoagulants are, however, commonly withheld due to a perceived risk of severe adverse events. The underutilization of anticoagulants in patients with AF has been demonstrated internationally, but to date, there are limited data available in the Australian context. The aim of this study was to determine the utilization patterns of anticoagulants (including novel oral anticoagulants) with respect to stroke and bleeding risk among patients with AF within the community. METHODS: We performed a nonexperimental, retrospective analysis designed to evaluate antithrombotic usage for AF in Australia. The utilization of antithrombotic therapy and the appropriateness of therapy were determined based on CHADS2, CHA2DS2-VASc and HAS-BLED risk stratification schemes. The presence of documented contraindications was used to determine the appropriateness of antithrombotic therapy. WHAT IS NEW AND CONCLUSION: Anticoagulants were overutilized in patients at low risk of stroke and underutilized in patients at higher risk of stroke. As the HAS-BLED score increased, the likelihood of patients receiving an anticoagulant decreased regardless of CHADS2 or CHA2DS2-VASc scores. PMID- 26994297 TI - Development of a Predictive Nomogram for the Change in PT/INR Upon Discontinuation of Bivalirudin as a Bridge to Warfarin. AB - Appropriate timing of bivalirudin discontinuation as a bridge to warfarin is complicated, as bivalirudin may cause a falsely prolonged international normalized ratio (INR). The purpose was to evaluate patient and medication characteristics associated with differences in INR prolongation caused by bivalirudin. Adult patients receiving bivalirudin as a bridge to warfarin in 2014 were retrospectively evaluated. Patients were excluded if they had known thrombophilia or inappropriate INR monitoring after discontinuation of bivalirudin. Data recorded included indication for bivalirudin use, bivalirudin dosing, and coagulation assays. Univariate analysis was performed to determine variables associated with a larger change in INR when discontinuing bivalirudin. Variables with P < .3 were included in multivariate analysis. In total, 50 patient admissions were included in the analysis. Patients with ventricular assist devices represented the majority of the patient population (74%). The most common INR goals were 2.0 to 3.0 and 2.5 to 3.5. The mean initial weight-based bivalirudin rate was 0.076 mg/kg/h, and the mean increase in INR when starting bivalirudin was 0.6. The mean final weight-based bivalirudin rate was 0.13 mg/kg/h, and the mean change in INR after stopping bivalirudin was 0.8. On multivariate analysis, factors associated with a larger change in INR after stopping bivalirudin included higher serum creatinine ( P = .033), greater change in INR after initiation of bivalirudin ( P = .028), and higher final bivalirudin rate ( P < .001). The change in INR when starting or stopping bivalirudin appears to be patient specific and dose related. A nomogram was developed to predict the ideal timing of bivalirudin discontinuation. Prospective evaluation of the nomogram is under way. PMID- 26994298 TI - Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients. AB - Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65-70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFalpha), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP ( p = 0.642) and TNFalpha ( p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not ( p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFalpha. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFalpha and pituitary hormones. PMID- 26994299 TI - Part I: Pituitary adenylate cyclase-activating polypeptide-38 induced migraine like attacks in patients with and without familial aggregation of migraine. AB - Background Intravenous infusion of adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine-like attacks in 65-70% of migraine sufferers. Whether aggregation of migraine in first-degree relatives contributes to this discrepancy in PACAP38-induced response is unknown. We hypothesized that genetic enrichment plays a role in triggering of migraine and that migraine without aura patients with a high family load ( >= 2 first-degree relatives with migraine) would report more migraine-like attacks after intravenous infusion of human PACAP38. Methods In this study, we allocated 32 previously genotyped migraine without aura patients to receive intravenous infusion of 10 pmol/kg/min PACAP38 and recorded migraine-like attacks including headache characteristics and associated symptoms. Information of familial aggregation was obtained by telephone interview of first degree relatives using a validated semi-structured questionnaire. Results PACAP38 infusion induced a migraine-like attack in 75% (nine out of 12) of patients with high family load compared to 70% (14 out of 20) with low family load ( P = 0.761). In an explorative investigation, we found that the migraine response after PACAP38 was not associated with the risk allele of rs2274316 ( MEF2D), which confers increased risk of migraine without aura and may regulate PACAP38 expression. Conclusion Migraine response to PACAP38 infusion in migraine without aura patients is not associated with high family load or the risk allele of rs2274316 ( MEF2D). PMID- 26994300 TI - Calcitonin gene-related peptide induced migraine attacks in patients with and without familial aggregation of migraine. AB - Background Calcitonin gene-related peptide provokes migraine attacks in 65% of patients with migraine without aura. Whether aggregation of migraine in first degree relatives (family load) or a high number of risk-conferring single nucleotide polymorphisms contributes to migraine susceptibility to calcitonin gene-related peptide infusion in migraine patients is unknown. We hypothesized that genetic enrichment plays a role in triggering of migraine and, therefore, migraine without aura patients with high family load would report more migraine attacks after calcitonin gene-related peptide infusion than patients with low family load. Methods We allocated 40 previously genotyped migraine without aura patients to receive intravenous infusion of 1.5 ug/min calcitonin gene-related peptide and recorded migraine attacks including headache characteristics and associated symptoms. Information of familial aggregation was obtained by telephone interview of first-degree relatives using a validated semi-structured questionnaire. Results Calcitonin gene-related peptide infusion induced a migraine-like attack in 75% (12 out of 16) of patients with high family load compared to 52% (12 out of 23) with low family load ( P = 0.150). In addition, we found that the migraine response after calcitonin gene-related peptide was not associated with specific or a high number of risk-conferring single nucleotide polymorphisms of migraine without aura. Conclusion We found no statistical association between familial aggregation of migraine and hypersensitivity to calcitonin gene-related peptide infusion in migraine without aura patients. We also demonstrated that the currently known single nucleotide polymorphisms conferring risk of migraine without aura have no additive effect on calcitonin gene-related peptide induced migraine-like attacks. PMID- 26994301 TI - Impact of obesity and binge eating disorder on patients with idiopathic intracranial hypertension. AB - Background Idiopathic intracranial hypertension (IIH) is associated with obesity, and obesity is associated with binge eating disorder (BED). The aim of this paper is to address the presence and impact of BED in patients undergoing an IIH diagnostic protocol. Methods This was a cross-sectional study. Consecutive patients suspected of IIH underwent neurological, neuro-ophthalmologic and psychological examinations, neuroimaging studies and intracranial pressure (ICP) measurements through lumbar puncture in the recumbent position. IIH diagnosis was based on International Classification of Headache Disorders, 2nd Edition criteria; BED diagnosis was based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid was also assessed. Results Forty-five patients were enrolled: 33 were diagnosed with IIH and five of them (15%) were obese with BED. Compared to non-obese patients, those who were obese, and particularly those who were obese with BED, were more likely to have an IIH diagnosis (chi2 = 14.3; p = 0.001), ICP > 200 mmH2O (chi2 = 12.7; p = 0.002) and history of abuse or neglect (chi2 = 11.2; p = 0.004). No association with OCBs was found. Conclusions We reported for the first time the presence of BED among patients with IIH and showed that BED is associated to IIH, ICP and history of abuse or neglect. PMID- 26994302 TI - Promiscuity Promotes Tolerance. PMID- 26994303 TI - Pillars Article: Promiscuous Gene Expression in Medullary Thymic Epithelial Cells Mirrors the Peripheral Self. Nat. Immunol. 2001. 2: 1032-1039. PMID- 26994304 TI - Human CD56bright NK Cells: An Update. AB - Human NK cells can be subdivided into various subsets based on the relative expression of CD16 and CD56. In particular, CD56(bright)CD16(-/dim) NK cells are the focus of interest. They are considered efficient cytokine producers endowed with immunoregulatory properties, but they can also become cytotoxic upon appropriate activation. These cells were shown to play a role in different disease states, such as cancer, autoimmunity, neuroinflammation, and infection. Although their phenotype and functional properties are well known and have been extensively studied, their lineage relationship with other NK cell subsets is not fully defined, nor is their precise hematopoietic origin. In this article, we summarize recent studies about CD56(bright) NK cells in health and disease and briefly discuss the current controversies surrounding them. PMID- 26994305 TI - Correction: Cutting Edge: Role of NK Cells and Surfactant Protein D in Dendritic Cell Lymph Node Homing: Effects of Ozone Exposure. PMID- 26994306 TI - Differential metallothionein, reduced glutathione and metal levels in Perna perna mussels in two environmentally impacted tropical bays in southeastern Brazil. AB - Mussel farming is an important economic activity in Brazil, and these organisms are consumed by the majority of the population in most coastal zones in the country. However, despite the increasing pollution of aquatic ecosystems in Brazil, little is known about the biochemical activity in mussels in response to metal exposure. In this context, the aim of the present study was to investigate metal and metalloid exposure effects in Perna perna mussels, by determining metal levels, the induction of metallothionein (MT) synthesis, and oxidative stress, in the form of reduced glutathione (GSH) in 3 contaminated areas from the Guanabara Bay in comparison to a reference site, Ilha Grande Bay, both in summer and winter. Metal and metalloid concentrations were also compared to Brazilian and international guidelines, to verify potential health risks to human consumers. Mussels from all sampling sites were shown to be improper for human consumption due to metal contamination, including Ilha Grande Bay, which has previously been considered a reference site. Several statistically significant correlations and seasonal differences were observed between MT, GSH and metals and metalloids in both analyzed tissues. A Discriminant Canonical Analysis indicated that the digestive gland is a better bioindicator for environmental contamination by metals and metalloids in this species and offers further proof that MT variations observed are due to metal exposure and not oxidative stress, since GSH influence for both muscle tissue and the digestive glands was non-significant in this analysis. These results show that P. perna mussels are an adequate sentinel species for metal contamination with significant effects on oxidative stress and metal exposure biomarkers. To the best of our knowledge, this is the first study to report metals, metalloids, MT and GSH levels in the muscle tissue of this species. PMID- 26994307 TI - Optimizing Use of Serum Prostate Specific Antigen to Define Biochemical Recurrence-Is There a Method to the Madness? PMID- 26994308 TI - Oncologic Equivalence between Laparoscopic/Robotic and Open Radical Cystectomy. PMID- 26994309 TI - The effect of interleukins 27 and 35 and their role on mediating the action of insulin Like Growth Factor -1 on the inflammation and blood flow of chronically inflamed rat knee joint. AB - INTRODUCTION: Previous studies have shown that some cytokines mediate the effect of IGF-1 on inflammation and also association between IGF-1 and vascular endothelial dysfunction. Due to the discrepancies in the inflammatory and anti inflammatory roles of IL-27 and IL-35, the effects of these cytokines and their IGF-1-mediating role were investigated regarding chronic joint inflammation and synovial blood flow. METHOD: Male rats were divided into two main groups of histopathology (n=80) and blood flow (n=72). These were further divided into ten subgroups of control, vehicle, IGF-1, IL-27, IL-35, their antagonists, IGF-1+IL 27 antagonist, and IGF-1+IL-35 antagonist. Inflammation was induced by intra articular injection of complete Freund adjuvant. Two weeks later (in order to induce chronic inflammation), vehicle or drugs were injected into the joint space every other day until day 28, on which inflammatory indices were assessed histopathologically. In the second subgroups, vehicle or drugs were administered by super-fusion on day 28 and their effects on the joint blood flow (JBF, laser Doppler perfusion method) and the systemic blood pressure were assessed. RESULTS: Endogenous IL-27 and IL-35 had inflammatory roles and IGF-1 had no effect. IL-27 and IL-35 antagonists had the highest anti-inflammatory and anti-angiogenesis effects and these effects were inhibited by IGF-1. Total inflammation score was 4.5 +/- 0.42, 3.50 +/- 0.5, 2.25 +/- 0.45 and 1.50 +/- 0.42 for vehicle, IGF-1 antagonist, IL-27 antagonist and IL-35 antagonist respectively. A significant increase was induced in JBF by IGF-1 antagonist and combination of IGF-1+IL-35 antagonist. CONCLUSION: IL-27 and IL-35 antagonists may be suitable goals for the treatment of chronic joint inflammation while their anti-inflammatory effects are not exerted via the changes in JBF. PMID- 26994310 TI - A method to induce Interleukin-1 Receptor Antagonist Protein from autologous whole blood. AB - OBJECTIVE: Current orthopedic therapies, aimed solely at symptomatic control, are unable to restore the cytokine imbalance that produces the hallmark clinical profile of osteoarthritis. While a myriad of chemical factors in the cytokine network stimulate local joint inflammation and pain, Interleukin 1 (IL-1) is widely recognized as a key offender and a potential therapeutic target. The purpose of this article is to describe a novel, on-site, point of service process (ArthrokinexTM) to induce Interleukin 1 Receptor Antagonist Protein (IL-1-Ra or IRAP) from whole blood aimed at inhibiting the destructive intra-articular effects of IL-1. METHODS: 53 patient charts were included in this retrospective chart review study. Venous blood from the selected participants had been harvested and centrifuged to isolate Platelet Rich Plasma and Platelet Poor Plasma. These layers were extracted and incubated for 30 min in a specialized syringe containing medical grade concentrator beads. After centrifuge filtration, the supernatant containing IL-1-Ra was extracted. Anti-inflammatory (IL-1-Ra, IL 10) and pro-inflammatory (TNF alpha, IL-1 beta) cytokines of baseline whole blood were compared to the conditioned serum following quantification using ELISA. RESULTS: On average, a 32-fold increase (baseline, 550 pg/mL; post conditioning 17,537 pg/mL) in IL-1-Ra concentration was observed after the brief interaction of blood with the concentrator bead surface. IL-1-Ra, if present in concentrations that are 10-100 times higher than IL-1beta, will block the interaction of IL-1beta with cell surface receptors. At these increased concentrations, ArthrokinexTM induced IL-1-Ra joint injections produce an IL-1-Ra to IL-1beta ratio of 999:1. Post conditioning levels of IL-1beta and TNF alpha were not clinically significant. CONCLUSION: The ArthrokinexTM blood conditioning process has the ability to rapidly induce IL-1-Ra without increasing the pro inflammatory cytokine profile. PMID- 26994311 TI - Wnt4 is required for ostia development in the Drosophila heart. AB - The Drosophila ostia are valve-like structures in the heart with functional similarity to vertebrate cardiac valves. The Wnt/beta-catenin signaling pathway is critical for valve development in zebrafish and mouse, but the key ligand(s) for valve induction remains unclear. We observed high levels of Wnt4 gene expression in Drosophila ostia progenitor cells, immediately prior to morphological differentiation of these cells associated with ostia formation. This differentiation was blocked in Wnt4 mutants and in flies expressing canonical Wnt signaling pathway inhibitors but not inhibitors of the planar cell polarity pathway. High levels of Wnt4 dependent activation of a canonical Wnt signaling reporter was observed specifically in ostia progenitor cells. In vertebrate valve formation Wnt signaling is active in cells undergoing early endothelial-mesenchymal transition (EMT) and the Wnt9 homolog of Drosophila Wnt4 is expressed in valve progenitors. In demonstrating an essential role for Wnt4 in ostia development we have identified similarities between molecular and cellular events associated with early EMT during vertebrate valve development and the differentiation and partial delamination of ostia progenitor cells in the process of ostia formation. PMID- 26994312 TI - Differential plasticity of size and mass to environmental change in a hibernating mammal. AB - Morphological changes following changes in species' distribution and phenology have been suggested to be the third universal response to global environmental change. Although structural size and body mass result from different genetic, physiological, and ecological mechanisms, they are used interchangeably in studies evaluating population responses to environmental change. Using a 22-year (1991-2013) dataset including 1768 individuals, we investigated the coupled dynamics of size and mass in a hibernating mammal, the Alpine marmot (Marmota marmota), in response to local environmental conditions. We (i) quantified temporal trends in both traits, (ii) determined the environmental drivers of trait dynamics, and (iii) identified the life-history processes underlying the observed changes. Both phenotypic traits were followed through life: we focused on the initial trait value (juvenile size and mass) and later-life development (annual change in size [Deltasize] and mass [Deltamass]). First, we demonstrated contrasting dynamics between size and mass over the study period. Juvenile size and subsequent Deltasize showed significant declines, whereas juvenile mass and subsequent Deltamass remained constant. As a consequence of smaller size associated with a similar mass, individuals were in better condition in recent years. Second, size and mass showed different sensitivities to environmental variables. Both traits benefited from early access to resources in spring, whereas Deltamass, particularly in early life, also responded to summer and winter conditions. Third, the interannual variation in both traits was caused by changes in early life development. Our study supports the importance of considering the differences between size and mass responses to the environment when evaluating the mechanisms underlying population dynamics. The current practice of focusing on only one trait in population modeling can lead to misleading conclusions when evaluating species' resilience to contemporary climate change. PMID- 26994313 TI - Classification of traditional Chinese pork bacon based on physicochemical properties and chemometric techniques. AB - Sixty-seven pork bacon samples from Hunan, Sichuan Guangdong, Jiangxi, and Yunnan Provinces in China were analyzed to understand their geographical properties. Classification was performed by determining their physicochemical properties through chemometric techniques, including variance analysis, principal component analysis (PCA), and discriminant analysis (DA). Results showed that certain differences existed in terms of nine physicochemical determinations in traditional Chinese pork bacon. PCA revealed the distinction among Hunan, Sichuan, and Guangdong style bacon. Meanwhile, seven key physicochemical determination criteria were identified in line with DA and could be reasonably applied to the classification of traditional Chinese pork bacon. Furthermore, the ratio of overall correct classification was 97.76% and that of cross-validation was 91.76%. These findings indicated that chemometric techniques, together with several physicochemical determination, were effective for the classification of traditional Chinese pork bacon with geographical features. Our study provided a theoretical reference for the classification of traditional Chinese pork bacon. PMID- 26994314 TI - Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen. AB - A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-gamma responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-gamma and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans. PMID- 26994315 TI - Validation of the board certification system for expert surgeons (hepato-biliary pancreatic field) using the data of the National Clinical Database of Japan: part 2 - Pancreatoduodenectomy. AB - BACKGROUND: Data of pancreatoduodenectomy (PD) cases from the National Clinical Database (NCD) were analyzed in order to validate the board certification system established by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). METHODS: Board-certified A training institutions and board-certified B training institutions were required to perform at least 50 and 30 high-level hepato-biliary-pancreatic (HBP) surgeries per year, respectively. Records of 17,563 patients who had undergone PD during 2011 and 2012 were retrospectively analyzed according to the category of the board-certified institution and with or without participation of board-certified instructors or expert surgeons. RESULTS: Operative mortality rates after PDs performed at certified A institutions, certified B institutions, and non-certified institutions were 1.5%, 3.0%, and 3.9%, respectively (P < 0.001). The operative mortality rates after PDs performed with participation of certified instructors or expert surgeons were better than those without (2.2% vs. 3.8%, P < 0.001). A multiple logistic regression model showed that cutoffs of high-level HBP surgeries performed per year at hospitals that predicted 30-day mortality after PDs were 10 and 50, and that those that predicted operative mortality were 10 and 70. CONCLUSIONS: The requirements for board-certified institutions, instructors, and expert surgeons to perform PD were appropriate. The requirements for board-certified A institutions were close to the identified cutoffs. Further analyses are necessary to elucidate the implications of the board certification system. PMID- 26994316 TI - The impact of tropical forest logging and oil palm agriculture on the soil microbiome. AB - Selective logging and forest conversion to oil palm agriculture are rapidly altering tropical forests. However, functional responses of the soil microbiome to these land-use changes are poorly understood. Using 16S rRNA gene and shotgun metagenomic sequencing, we compared composition and functional attributes of soil biota between unlogged, once-logged and twice-logged rainforest, and areas converted to oil palm plantations in Sabah, Borneo. Although there was no significant effect of logging history, we found a significant difference between the taxonomic and functional composition of both primary and logged forests and oil palm. Oil palm had greater abundances of genes associated with DNA, RNA, protein metabolism and other core metabolic functions, but conversely, lower abundance of genes associated with secondary metabolism and cell-cell interactions, indicating less importance of antagonism or mutualism in the more oligotrophic oil palm environment. Overall, these results show a striking difference in taxonomic composition and functional gene diversity of soil microorganisms between oil palm and forest, but no significant difference between primary forest and forest areas with differing logging history. This reinforces the view that logged forest retains most features and functions of the original soil community. However, networks based on strong correlations between taxonomy and functions showed that network complexity is unexpectedly increased due to both logging and oil palm agriculture, which suggests a pervasive effect of both land-use changes on the interaction of soil microbes. PMID- 26994317 TI - The fluorescence and resonance Rayleigh scattering spectral study and analytical application of cerium (IV) and cefoperazone system. AB - In weak acidic medium of pH3.5-5.6, Ce(IV) can be reduced by cefoperazone (CPZ) to be Ce(III), which further combined with CPZ to form complex Ce(OH)3CPZ. This complex not only has higher fluorescence than Ce(III), but also results in significant increase of resonance Rayleigh scattering (RRS), second order scattering (SOS) and frequency doubling scattering (FDS). The wavelengths of maximum fluorescence exciting and emission are located at 356 nm/349 nm, while the maximum wavelengths of RRS, SOS and FDS are at 312 nm, 550 nm and 390 nm, respectively. The intensity of fluorescence and scattering are all linear with the concentration of CPZ in certain conditions. The detection limit of most sensitive RRS method for CPZ is 2.1 ng mL(-1). The optimum conditions for detecting CPZ using RRS method are investigated. The effect of co-existing substances shows that the method has excellent selectivity, especially since other cephalosporins don't have similar reactions. Therefore, it can be achieved to determine CPZ in cephalosporins selectively. The paper also focuses on the reaction mechanism, the consistent and contracture of the resultant. The reasons for enhanced intensity are presumed in the meantime. PMID- 26994318 TI - Determination of phenformin hydrochloride employing a sensitive fluorescent probe. AB - A complexation of non-fluorescent phenformin hydrochloride (PFH) with cucurbit [7]uril (CB [7]) in aqueous solution was investigated using the fluorescent probe of palmatine (PAL) coupled with CB [7]. The fluorescent probe of CB [7]-PAL exhibited strong fluorescence in aqueous solution, which was quenched gradually with the increase of PFH. This effect is observed because when PFH was added to the host-guest system of CB [7]-PAL, PFH and PAL competed to occupy the CB [7] cavity. Portions of the PAL molecule were expelled from the CB [7] cavity owing to the introduction of PFH. Based on the significant quenching of the supramolecular complex fluorescence intensity, a fluorescence method of high sensitivity and selectivity was developed to determine PFH with good precision and accuracy for the first time. The linear range of the method was 0.005-1.9 MUg mL(-1) with a detection limit of 0.003 MUg mL(-1). In this work, association constants (K) of PFH with CB [7] were also determined. KCB [7]-PFH=(2.52+/ 0.05)*10(5) L mol(-1). The ability of PFH to bind with CB [7] is stronger than that of PAL. The results of a density functional theory calculation authenticated that the moiety of PFH was embedded in the hydrophobic cavity of CB [7] tightly, and the nitrogen atom is located in the vicinity of a carbonyl-laced portal in the energy-minimized structure. The molecular modelling of the interaction between PFH and CB [7] was also confirmed by (1)H NMR spectra (Bruker 600 MHz). PMID- 26994319 TI - Crystal chemical correlations between the mid and near-infrared in carbonate minerals. AB - Near-infrared (NIR) spectra of carbonates have proved important in many disciplines including planetary exploration. Classically bands in the 4000-6000 cm(-1) (2.5-1.67 MUm) region are assigned to [CO3(2-)] internal mode combinations and overtones. However band assignments remain equivocal. This study examines three prominent bands ((ca 4505 cm(-1) (2.219 MUm), 4900 cm(-1) (2.041 MUm) and 5145 cm(-1) (1.944 MUm)) from powdered calcite and aragonite group minerals. Results indicate that the bands originate from anharmonic coupling of degenerate internal mode(s) with external (lattice) modes. On this basis it is suggested that NIR data may provide an untapped source of detailed information on lattice mode frequencies and information on the type(s) of the environmental cation(s) in carbonate minerals. PMID- 26994320 TI - A UHPLC-UV-QTOF study on the stability of carfilzomib, a novel proteasome inhibitor. AB - This study addresses the lack of data on the stability of carfilzomib, a newly approved proteasome-inhibiting anticancer drug. A new stability-indicating UHPLC UV method for analysis of carfilzomib was developed and validated within the concentrations of 10-250 MUg/mL. The aforementioned method was utilized to evaluate the effects of forced degradation and to investigate the degradation kinetics, as well as to examine drug stability in a pharmaceutical formulation. A UHPLC-QTOF method was utilized to identify the principal degradation products. It was found that carfilzomib: (1) is stable at neutral and slightly acidic pH, but prone to degradation at both high and low pH; (2) is acceptably stable in the pharmaceutical formulation; but (3) is prone to oxidation and photodegradation. Carfilzomib degradation followed first-order kinetics. The decomposition products resulted from peptide bond hydrolysis, epoxide hydrolysis, hydrogen chloride addition, base-catalyzed Robinson-Gabriel reaction, tertiary amine oxidation and isomerization. Our results document, for the first time, the inherent stability of carfilzomib and provide information about the identity of its degradation products. These results highlight the stability issues that need to be kept in mind for handling and storage of carfilzomib. PMID- 26994321 TI - Deep ploughing increases agricultural soil organic matter stocks. AB - Subsoils play an important role within the global C cycle, since they have high soil organic carbon (SOC) storage capacity due to generally low SOC concentrations. However, measures for enhancing SOC storage commonly focus on topsoils. This study assessed the long-term storage and stability of SOC in topsoils buried in arable subsoils by deep ploughing, a globally applied method for breaking up hard pans and improving soil structure to optimize crop growing conditions. One effect of deep ploughing is translocation of SOC formed near the surface into the subsoil, with concomitant mixing of SOC-poor subsoil material into the 'new' topsoil. Deep-ploughed croplands represent unique long-term in situ incubations of SOC-rich material in subsoils. In this study, we sampled five loamy and five sandy soils that were ploughed to 55-90 cm depth 35-50 years ago. Adjacent, similarly managed but conventionally ploughed subplots were sampled as reference. The deep-ploughed soils contained on average 42 +/- 13% more SOC than the reference subplots. On average, 45 years after deep ploughing, the 'new' topsoil still contained 15% less SOC than the reference topsoil, indicating long term SOC accumulation potential in the topsoil. In vitro incubation experiments on the buried sandy soils revealed 63 +/- 6% lower potential SOC mineralisation rates and also 67 +/- 2% lower SOC mineralisation per unit SOC in the buried topsoils than in the reference topsoils. Wider C/N ratio in the buried sandy topsoils than in the reference topsoils indicates that deep ploughing preserved SOC. The SOC mineralisation per unit SOC in the buried loamy topsoils was not significantly different from that in the reference topsoils. However, 56 +/- 4% of the initial SOC was preserved in the buried topsoils. It can be concluded that deep ploughing contributes to SOC sequestration by enlarging the storage space for SOC-rich material. PMID- 26994322 TI - Janus kinase inhibitors for rheumatoid arthritis. AB - Treatment of autoimmune diseases, such as rheumatoid arthritis (RA), has advanced substantially over the past decade with the development of biologics targeting inflammatory cytokines. Recent progress in treating RA has been achieved with janus kinase (JAK) inhibitors (Jakinibs), an orally available disease-modifying anti-rheumatic drug targeting the intracellular kinase JAK and with similar efficacy to biologics. The first Jakinib approved for RA was tofacitinib, which exerted superiority to methotrexate and non-inferiority to tumor necrosis factor (TNF) inhibitors. In recent years, the Jakinib baricitinib has demonstrated superiority to both methotrexate and a TNF inhibitor, adalimumab. Given these promising findings, Jakinibs are expected to represent the next generation compounds for treating RA, and a number of Jakinibs are currently in clinical trials. Jakinibs can differ substantially in their selectivity against JAKs; tofacitinib and baricitinib target multiple JAKs, whereas the most recently developed Jakinibs target only a single JAK. The influence of Jakinib selectivity on efficacy and side effects is of great interest, requiring further careful observation. PMID- 26994323 TI - Atrial fibrillation associated with ibrutinib in Waldenstrom macroglobulinemia. PMID- 26994324 TI - Translational control by eIF2alpha in neurons: Beyond the stress response. AB - The translation of mRNAs is a tightly controlled process that responds to multiple signaling pathways. In neurons, this control is also exerted locally due to the differential necessity of proteins in axons and dendrites. The phosphorylation of the alpha subunit of the translation initiation factor 2 (eIF2alpha) is one of the mechanisms of translational control. The phosphorylation of eIF2alpha has classically been viewed as a stress response, halting translation initiation. However, in the nervous system this type of regulation has been related to other mechanisms besides stress response, such as behavior, memory consolidation and nervous system development. Additionally, neurodegenerative diseases have a major stress component, thus eIF2alpha phosphorylation plays a preeminent role and its modulation is currently viewed as a new opportunity for therapeutic interventions. This review consolidates current information regarding eIF2alpha phosphorylation in neurons and its impact in neurodegenerative diseases. (c) 2016 Wiley Periodicals, Inc. PMID- 26994325 TI - New perspectives on complement mediated immunotherapy. AB - Tumor-specific monoclonal antibodies (mAbs) offer several modes of tumor cell killing, from direct cytotoxic activity to indirect mechanisms employing the host immune system, particularly its innate branch. The latter effector functions seem to dominate among clinically approved anti-cancer mAbs and major efforts are being undertaken by both academia and the pharmaceutical industry with the aim to improve complement activation, antibody-dependent cellular cytotoxicity (ADCC) and Fc/opsonin-mediated phagocytosis. On one hand, there are a variety of available effector mechanisms to allow multistep elimination of tumor cells. On the other hand, tumor cells adopt a number of strategies to evade immune attack, such as overexpression of complement inhibitors, trogocytosis, shedding or internalization of mAb-targeted epitopes, which all contribute to their resistance against host defense mechanisms. Another problem recognized only recently is the depletion of immune effectors during the first round of treatment, which in concordance with delayed turnover of immune components renders subsequent rounds of therapy ineffective. Herein, we discuss newly identified limiting factors but also novel mechanistic data on complement activation by antitumor antibodies as issues important for guidance towards the next generations of immunotherapeutics. PMID- 26994326 TI - Response to Wheatley et al., "Surgical excision margins in primary cutaneous melanoma: A meta-analysis and Bayesian probability evaluation", Cancer Treatment Reviews. PMID- 26994327 TI - Characterization of chemical components and bioreactivity of fine particulate matter (PM2.5) during incense burning. AB - The chemical and bioreactivity properties of fine particulate matter (PM2.5) emitted during controlled burning of different brands of incense were characterized. Incenses marketed as being environmentally friendly emitted lower mass of PM2.5 particulates than did traditional incenses. However, the environmentally friendly incenses produced higher total concentrations of non volatile polycyclic aromatic hydrocarbons (PAHs) and some oxygenated polycyclic aromatic hydrocarbons (OPAHs). Human alveolar epithelial A549 cells were exposed to the collected PM2.5, followed by determining oxidative stress and inflammation. There was moderate to strong positive correlation (R > 0.60, p < 0.05) between selected PAHs and OPAHs against oxidative-inflammatory responses. Strong positive correlation was observed between interleukin 6 (IL-6) and summation of total Group B2 PAHs/OPAHs (?7PAHs/SigmaOPAHs). The experimental data indicate that emissions from the environmentally friendly incenses contained higher concentrations of several PAH and OPAH compounds than did traditional incense. Moreover, these PAHs and OPAHs were strongly correlated with inflammatory responses. The findings suggest a need to revise existing regulation of such products. PMID- 26994328 TI - Microstructure, crystallography and diagenetic alteration in fossil ostrich eggshells from Upper Palaeolithic sites of Indian peninsular region. AB - Biominerals studies are of importance as they provide an understanding of natural evolutionary processes. In this study we have investigated the fossil ostrich eggshells using Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Electron Backscatter Diffraction (EBSD). SEM studies demonstrated the ultrastructure of fossil eggshells and formation of calcified cuticular layer. The presence of calcified cuticle layer in eggshell is the basis for ancient DNA studies as it contains preserved biomolecules. EBSD accentuates the crystallographic structure of the ostrich eggshells with sub-micrometer resolution. It is a non-destructive tool for evaluating the extent of diagenesis in a biomineral. EBSD analysis revealed the presence of dolomite in the eggshells. This research resulted in the complete recognition of the structure of ostrich eggshells as well as the nature and extent of diagenesis in these eggshells which is vital for genetic and paleoenvironmental studies. PMID- 26994329 TI - Solanesol extraction from tobacco leaves by Flash chromatography based on molecularly imprinted polymers. AB - A novel solanesol extraction method based on molecularly imprinted polymer (MIP) as the Flash chromatography stationary phase was established and evaluated. Spherical MIP particles in a size range of 250-350 MUm (d (0.5)=320 MUm) for solanesol were synthesized by suspension polymerization, with imprinting factor of 3.9. The MIP particles (5.5 g) were packed in common Teflon column as the stationary phase while the sample solution and elution solvent were confirmed as methanol and methanol/acetic acid solution (80/20, v/v), loading at 4 ml/min and eluting 8 ml/min, respectively. Under the optimal chromatographic conditions, the adsorption capacity of the MIP-Flash column was determined as 107.3 MUmol/g, and in each process, 370.8 mg purified solanesol (98.4%) could be obtained from the extract (20 mM, 40 ml) of tobacco leaves (14.7 g), and the yield of solanesol was 2.5% of the dry weight of tobacco leaves. The results reported here confirm the feasibility to extract highly purified active ingredients directly from natural products on a large scale by MIP-Flash chromatography. PMID- 26994330 TI - Determination of "new psychoactive substances" in postmortem matrices using microwave derivatization and gas chromatography-mass spectrometry. AB - Despite worldwide efforts aiming to ban the marketing and subsequent abuse of psychoactive substances such as synthetic cathinones and phenethylamines, there has been an alarming growth of both in recent years. Different compounds similar to those already existing are continuously appearing in the market in order to circumvent the legislation. An analytical methodology has been validated for qualitative and quantitative determinations of D-cathine (D-norpseudoehedrine), ephedrine, methcathinone, 1-(4-methoxyphenyl)-propan-2-amine (PMA), mephedrone, methedrone, 2,5-dimethoxy-4-methylamphetamine (DOM), 4-bromo-2,5 dimethoxyamphetamine (DOB), 2,5-dimethoxyphenethylamine (2C-H), 4-bromo-2,5 dimethoxyphenethylamine (2C-B), 4-iodo-2,5-dimethoxyphenethylamine (2C-I), 2-[2,5 dimethoxy-4-(ethylthio)phenyl]ethanamine (2C-T-2), 2,5-dimethoxy-4 isopropylthiophenethylamine (2C-T-4) and 2-[2,5-dimethoxy-4 (propylthio)phenyl]ethanamine (2C-T-7), in low volumes of vitreous humor (100 MUL), pericardial fluid (250 MUL) and whole blood (250 MUL), using deutered amphetamine, ephedrine and mephedrone as internal standards. The validation parameters included selectivity, linearity and limits of detection and quantification, intra- and interday precision and trueness, recovery and stability. The method included mixed-mode solid phase extraction, followed by microwave fast derivatization and analysis by gas chromatography-mass spectrometry operated in selected ion monitoring mode. The procedure was linear between 5 and 600 ng/mL, with determination coefficients higher than 0.99 for all analytes. Intra- and interday precision ranged from 0.1 to 13.6%, while accuracy variability was within 80-120% interval from the nominal concentration at all studied levels. The extraction efficiencies ranged from 76.6 to 112.8%. Stability was considered acceptable for all compounds in the studied matrices. The developed assay was applied to authentic samples of the Laboratory of Chemistry and Forensic Toxicology, Centre Branch, of the National Institute of Legal Medicine and Forensic Sciences, Portugal. PMID- 26994331 TI - Optimization of a gas chromatography-mass spectrometry method with methyl chloroformate derivatization for quantification of amino acids in plant tissue. AB - Rapid, easy and reliable quantification of amino acids is crucial in research on plant amino acid metabolism and nutritional improvement of crops via enrichment of essential amino acids. A recently reported analysis method, based on solid phase extraction (SPE), derivatization with methyl chloroformate and gas chromatography-mass spectrometry was optimized and tested on three-week-old Arabidopsis thaliana leaf tissues. Optimization of the SPE cleanup yielded recovery rates of minimum 95% for all amino acids (except arginine). Variations in accuracy and precision did not exceed 12.5%, except for cysteine, histidine and tryptophane, which were excluded from analysis. Quantification of overlapping peaks for isoleucine/threonine and proline/asparagine was possible by selection of two specific fragment ions for each amino acid. Of the 16 selected amino acids, 14 were quantified successfully in at least 75% of the samples, while methionine and tyrosine were only quantifiable in 6% and 42%, respectively. A case study on the aspartate super pathway confirmed the applicability of the optimized method on wild type and genetically modified plants: external supplementation of methionine or lysine yielded a 146-fold or 27-fold increase in the respective absolute amino acid levels compared with the control treatment. Induced expression of dhdps-r1 (a mutated lysine biosynthesis gene encoding a feedback insensitive enzyme) caused an 83-fold increase in absolute lysine levels. PMID- 26994332 TI - Turn-off fluorescence sensor for the detection of ferric ion in water using green synthesized N-doped carbon dots and its bio-imaging. AB - This paper reports turn-off fluorescence sensor for Fe(3+) ion in water using fluorescent N-doped carbon dots as a probe. A simple and efficient hydrothermal carbonization of Prunus avium fruit extract for the synthesis of fluorescent nitrogen-doped carbon dots (N-CDs) is described. This green approach proceeds quickly and provides good quality N-CDs. The mean size of synthesized N-CDs was approximately 7nm calculated from the high-resolution transmission electron microscopic images. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy revealed the presence of -OH, -NH2, -COOH, and -CO functional groups over the surface of CDs. The N-CDs showed excellent fluorescent properties, and emitted blue fluorescence at 411nm upon excitation at 310nm. The calculated quantum yield of the synthesized N-CDs is 13% against quinine sulfate as a reference fluorophore. The synthesized N-CDs were used as a fluorescent probe towards the selective and sensitive detection of biologically important Fe(3+) ions in water by fluorescence spectroscopy and for bio-imaging of MDA-MB 231 cells. The limit of detection (LOD) and the Stern-Volmer quenching constant for the synthesized N-CDs were 0.96MUM and 2.0958*10(3)M of Fe(3+) ions. The green synthesized N-CDs are efficiently used as a promising candidate for the detection of Fe(3+) ions and bio-imaging. PMID- 26994333 TI - Synthesis and properties of 5,10,15,20-tetrakis[4-(3-N,N dimethylaminopropoxy)phenyl] chlorin as potential broad-spectrum antimicrobial photosensitizers. AB - A novel 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]chlorin (TAPC) was synthesized by reduction of the corresponding porphyrin TAPP with p toluenesulfonhydrazide, followed by selective oxidation with o-chloranil. Spectroscopic properties and the photodynamic activity of these photosensitizers were compared in N,N-dimethylformamide. An increase in the absorption band at 650nm was found for the chlorin derivative with respect to TAPP. These photosensitizers emit red fluorescence with quantum yields of 0.15. Both compounds were able to photosensitize singlet molecular oxygen with quantum yields of about 0.5. Also, the formation of superoxide anion radical was detected in the presence of TAPC or TAPP and NADH. Photodynamic inactivation was investigated on a Gram-positive bacterium Staphylococcus aureus, a Gram-negative bacterium Escherichia coli and a fungal yeast Candida albicans cells. In vitro experiments showed that TAPC or TAPP were rapidly bound to microbial cells at short incubation periods. These photosensitizers, without intrinsic positive charges, contain four basic amino groups. These substituents can be protonated at physiological pH, increasing the interaction with the cell envelopment. Photosensitized inactivation improved with an increase of both photosensitizer concentrations and irradiation times. After 15min irradiation, a 7 log reduction of S. aureus was found for treated with 1MUM photosensitizer. Similar result was obtained with E. coli after using 5MUM photosensitizer and 30min irradiation. Also, the last conditions produced a decrease of 5 log in C. albicans cells. Therefore, TAPC was highly effective as a broad-spectrum antimicrobial photosensitizer. PMID- 26994334 TI - Effect of photoactivated disinfection using light in the blue spectrum. AB - BACKGROUND: Light in the blue spectrum is well known to cure composites. This in vitro-study was aimed to analyze a potential antimicrobial activity when combined with riboflavin as a photosensitizer. METHODS: Photoactivated disinfection (PAD) using a LED lamp emitting in the blue spectrum for 30s (PAD30) and 60s (PAD60) after application of 0.1% riboflavin was compared with a LED lamp emitting in the red spectrum with the respective photosensitizer (PADred). Killing activity was analyzed against planktonic 14 single species and a 12-species mixture with and without 25% serum. In addition, there was a reduction of viable bacterial counts in single species and a 12-species biofilm was measured after PAD. RESULTS: Gram positive bacteria were less sensitive to PAD30 and PAD60 than Gram-negatives. PAD60 decreased the counts by more than 3log10cfu in two of five Gram-positive and in six of nine Gram-negative strains, the total viable counts of the mixture were reduced by 1.04+/-0.46log10cfu. In the presence of 25% serum a decrease by more than 2log10cfu was only found in tests with one Porphyromonas gingivalis strain. PADred killed all included strains except for the 12-species mixture and Eubacterium nodatum. PAD60 reduced the counts in P. gingivalis biofilms by 2 3log10cfu, however there was no activity of PAD60 and PADred on the multi-species biofilm. CONCLUSIONS: PAD using LED emitting in the blue spectrum combined with riboflavin is active against periodontopathogenic microbial species but clearly inferior to PADred. Multi-species biofilms are not sensitive to PAD using LED. PMID- 26994335 TI - A novel method developed for estimating mineralization efficiencies and its application in PC and PEC degradations of large molecule biological compounds with unknown chemical formula. AB - A new method to estimate the photocatalytic (PC) and photoelectrocatalytic (PEC) mineralization efficiencies of large molecule biological compounds with unknown chemical formula in water was firstly developed and experimentally validated. The method employed chemical oxidation under the standard dichromate chemical oxygen demand (COD) conditions to obtain QCOD values of model compounds with unknown chemical formula. The measured QCOD values were used as the reference to replace QCOD values of model compounds for calculation of the mineralization efficiencies (in %) by assuming the obtained QCOD values are the measure of the theoretical charge required for the complete mineralization of organic pollutants. Total organic carbon (TOC) was also employed as a reference to confirm the mineralization capacity of dichromate chemical oxidation. The developed method was applied to determine the degradation extent of model compounds, such as bovine serum albumin (BSA), lecithin and bacterial DNA, by PC and PEC. Incomplete PC mineralization of all large molecule biological compounds was observed, especially for BSA. But the introduction of electrochemical technique into a PC oxidation process could profoundly improve the mineralization efficiencies of model compounds. PEC mineralization efficiencies of bacterial DNA was the highest, while that of lecithin was the lowest. Overall, PEC degradation method was found to be much effective than PC method for all large molecule biological compounds investigated, with PEC/PC mineralization ratios followed an order of BSA > lecithin > DNA. PMID- 26994336 TI - Predicting the apparent viscosity and yield stress of digested and secondary sludge mixtures. AB - The legal banning of conventional sludge disposal methods such as landfill has led to a global movement towards achieving a sustainable sludge management strategy. Reusing sludge for energy production (biogas production) through the anaerobic digestion of sludge can provide a sustainable solution. However, for the optimum performance of digesters with minimal use of energy input, operating conditions must be regulated in accordance with the rheological characteristics of the sludge. If it is assumed that only secondary sludge enters the anaerobic digesters, an impact of variations to the solids concentration and volume fraction of each sludge type must be investigated to understand how the apparent viscosity and yield stress of the secondary and digested sludge mixture inside the digesters changes. In this study, five different total solids concentration of secondary and digested sludge were mixed at different digested sludge volume fractions ranging from 0 to 1. It was found that if secondary sludge was mixed with digested sludge at the same total solids concentration, the apparent viscosity and the yield stress of the mixture increased exponentially by increasing the volume fraction of digested sludge. However, if secondary sludge was added to digested sludge with a different solids concentration, the apparent viscosity and yield stress of the resulting mixed sludge was controlled by the concentrated sludge regardless of its type. Semi - empirical correlations were proposed to predict the apparent viscosity and yield stress of the mixed digested and secondary sludge. A master curve was also developed to predict the flow behaviour of sludge mixtures regardless of the total solid concentration and volume fraction of each sludge type within the studied solids concentration range of 1.4 and 7%TS. This model can be used for digesters optimization and design by predicting the rheology of sludge mixture inside digester. PMID- 26994337 TI - Impact of the morphology and reactivity of nanoscale zero-valent iron (NZVI) on dechlorinating bacteria. AB - Nanoscale zero-valent iron (NZVI) is increasingly used for reducing chlorinated organic contaminants in soil or groundwater. However, little is known about what impact the particles will have on the biochemical processes and the indigenous microbial communities. Nanoiron reactivity is affected by the structure and morphology of nanoparticles that complicates the applicability in bioremediation. In this study, the effect of precursors (ferrous sulfate and ferric chloride) and reducing agents (sodium dithionite and sodium borohydride) on the morphology and the reactivity of NZVIs was investigated. We also studied the impact of differently synthesized NZVIs on microbial community, which take part in reductive dechlorination. We demonstrated that both the applied iron precursor and the reducing agent had influence on the structure of the nanoparticles. Spherical nanoparticles with higher Fe(0) content (>90%) was observed by using sodium borohydride as reducing agent, while application of sodium dithionite as reducing agent resulted nanostructures with lower Fe(0) content (between 68,7 and 85,5%). To determine the influence of differently synthesized NZVIs on cell viability anaerobic enriched microcosm were used. NVZI was used in 0.1 g/L concentration in all batch experiments. Relative amount of Dehalococcoides, sulfate reducers (SRBs) and methanogens were measured by quantitative PCR. We found that the relative amount of Dehalococcoides slowly decreased in all experiments independently from the precursor and reducing agent, whereas the total amount of microbes increased. The only clear distinction was in relative amount of sulfate reducers which were higher in the presence of NZVIs synthesized from sodium dithionite. PMID- 26994338 TI - External potassium (K(+)) application improves salinity tolerance by promoting Na(+)-exclusion, K(+)-accumulation and osmotic adjustment in contrasting peanut cultivars. AB - Achieving salt-tolerance is highly desirable in today's agricultural context. Apart from developing salt-tolerant cultivars, possibility lies with management options, which can improve crop yield and have significant impact on crop physiology as well. Thus present study was aimed to evaluate the ameliorative role of potassium (K(+)) in salinity tolerance of peanut. A field experiment was conducted using two differentially salt-responsive cultivars and three levels of salinity treatment (control, 2.0 dS m(-1), 4.0 dS m(-1)) along with two levels (with and without) of potassium fertilizer (0 and 30 kg K2O ha(-1)). Salinity treatment incurred significant changes in overall physiology in two peanut cultivars, though the responses varied between the tolerant and the susceptible one. External K(+) application resulted in improved salinity tolerance in terms of plant water status, biomass produced under stress, osmotic adjustment and better ionic balance. Tolerant cv. GG 2 showed better salt tolerance by excluding Na(+) from uptake and lesser accumulation in leaf tissue and relied more on organic osmolyte for osmotic adjustment. On the contrary, susceptible cv. TG 37A allowed more Na(+) to accumulate in the leaf tissue and relied more on inorganic solute for osmotic adjustment under saline condition, hence showed more susceptibility to salinity stress. Application of K(+) resulted in nullifying the negative effect of salinity stress with slightly better response in the susceptible cultivar (TG 37A). The present study identified Na(+)-exclusion as a key strategy for salt-tolerance in tolerant cv. GG 2 and also showed the ameliorating role of K(+) in salt-tolerance with varying degree of response amongst tolerant and susceptible cultivars. PMID- 26994339 TI - Childhood adversity and psychiatric disorder in young adulthood: An analysis of 107,704 Swedes. AB - Childhood adversity (CA) is associated with increased risks of psychiatric disorder in young adulthood, but details in this association are less known. We aimed to explore the association of a range of CA indicators with psychiatric disorder in young adulthood, and the impact of age at exposure, disorder type and accumulation of indicators. We capitalized on Sweden's extensive and high-quality registers and analyzed a cohort of all Swedes (N = 107,704) born in Stockholm County 1987-1991. Adversities included familial death, parental substance misuse and psychiatric disorder, parental criminality, parental separation, public assistance recipiency and residential instability. Age at exposure was categorized as: 0-6.9 years (infancy and early childhood), 7-11.9 years (middle childhood), and 12-14 years (early adolescence). Psychiatric disorders after age 15 were defined from ICD codes through registers. Risks were calculated as Hazard Ratios (HR) with 95% confidence intervals (CI). Results showed that exposure to at least one CA was associated with an increased risk of psychiatric disorder (HR 1.4, 95% CI: 1.3-1.4). Risks were increased for mood, anxiety, and psychotic disorders and ADHD but not for eating disorders. The risk varied with type of disorder but was similar for all exposure periods. Individuals with multiple (3+) CAs had a two-fold risk of psychiatric disorder (HR 2.0, 95% CI: 1.9-2.1). In conclusion, our findings support the long-term negative impact of CA on mental health, regardless of developmental period of exposure. Given that experience of CA is common, efforts should be put to alleviate the burden of childhood adversities for children, particularly among the most disadvantaged. PMID- 26994341 TI - Urinary zinc loss in sickle cell disease primarily due to increased bone degradation. PMID- 26994342 TI - Demographic history of speciation in a Senecio altitudinal hybrid zone on Mt. Etna. AB - Hybrid zones typically form as a result of species coming into secondary contact, but can also be established in situ as an ecotonal hybrid zone, a situation which has been reported far less frequently. An altitudinal hybrid zone on Mount Etna between two ragwort species (the low elevation Senecio chrysanthemifolius and high elevation S. aethnensis) could potentially represent either of these possibilities. However, a scenario of secondary contact vs. speciation with gene flow has not been explicitly tested. Here, we test these alternatives and demonstrate that the data do not support secondary contact. Furthermore, we report that the previous analyses of speciation history of these species were based on admixed populations, which has led to inflated estimates of ongoing, interspecific gene flow. Our new analyses, based on 'pure' S. aethnensis and S. chrysanthemifolius populations, reveal gene exchange of less than one effective migrant per generation, a level low enough to allow the species to accumulate neutral, genomewide differences. Overall, our results are consistent with a scenario of speciation with gene flow and a divergence time which coincides with the rise of Mt. Etna to altitudes above 2000 m (~150 KY). Further work to quantify the role of adaptation to contrasting environments of high and low altitudes will be needed to support the scenario of recent ecological speciation in this system. PMID- 26994340 TI - Relationship of optimism and suicidal ideation in three groups of patients at varying levels of suicide risk. AB - Optimism has been associated with reduced suicidal ideation, but there have been few studies in patients at high suicide risk. We analyzed data from three study populations (total N = 319) with elevated risk of suicide: (1) patients with a recent acute cardiovascular event, (2) patients hospitalized for heart disease who had depression or an anxiety disorder, and (3) patients psychiatrically hospitalized for suicidal ideation or following a suicide attempt. For each study we analyzed the association between optimism (measured by the Life-Orientation Test-Revised) and suicidal ideation, and then completed an exploratory random effects meta-analysis of the findings to synthesize this data. The meta-analysis of the three studies showed that higher levels of self-reported optimism were associated with a lower likelihood of suicidal ideation (odds ratio [OR] = .89, 95% confidence interval [CI] = .85-.95, z = 3.94, p < .001), independent of age, gender, and depressive symptoms. This association held when using the subscales of the Life Orientation Test-Revised scale that measured higher optimism (OR = .84, 95% CI = .76-.92, z = 3.57, p < .001) and lower pessimism (OR = .83, 95% CI = .75-.92], z = 3.61, p < .001). These results also held when suicidal ideation was analyzed as an ordinal variable. Our findings suggest that optimism may be associated with a lower risk of suicidal ideation, above and beyond the effects of depressive symptoms, for a wide range of patients with clinical conditions that place them at elevated risk for suicide. PMID- 26994343 TI - A Unique Role for Endothelial Cell Kinesin Light Chain 1, Variant 1 in Leukocyte Transendothelial Migration. AB - A reservoir of parajunctional membrane in endothelial cells, the lateral border recycling compartment (LBRC), is critical for transendothelial migration (TEM). We have previously shown that targeted recycling of the LBRC to the site of TEM requires microtubules and a kinesin molecular motor. However, the identity of the kinesin and mechanism of cargo binding were not known. We show that microinjection of endothelial cells with a monoclonal antibody specific for kinesin-1 significantly blocked LBRC-targeted recycling and TEM. In complementary experiments, knocking down KIF5B, a ubiquitous kinesin-1 isoform, in endothelial cells significantly decreased targeted recycling of the LBRC and leukocyte TEM. Kinesin heavy chains move cargo along microtubules by one of many kinesin light chains (KLCs), which directly bind the cargo. Knocking down KLC 1 isoform variant 1 (KLC1C) significantly decreased LBRC-targeted recycling and TEM, whereas knocking down other isoforms of KLC1 had no effect. Re-expression of KLC1C resistant to the knockdown shRNA restored targeted recycling and TEM. Thus kinesin-1 and KLC1C are specifically required for targeted recycling and TEM. These data suggest that of the many potential combinations of the 45 kinesin family members and multiple associated light chains, KLC1C links the LBRC to kinesin-1 (KIF5B) during targeted recycling and TEM. Thus, KLC1C can potentially be used as a target for anti-inflammatory therapy. PMID- 26994344 TI - Canceled connections: Lesion-derived network mapping helps explain differences in performance on a complex decision-making task. AB - Studies of patients with brain damage have highlighted a broad neural network of limbic and prefrontal areas as important for adaptive decision-making. However, some patients with damage outside these regions have impaired decision-making behavior, and the behavioral impairments observed in these cases are often attributed to the general variability in behavior following brain damage, rather than a deficit in a specific brain-behavior relationship. A novel approach, lesion-derived network mapping, uses healthy subject resting-state functional connectivity (RSFC) data to infer the areas that would be connected with each patient's lesion area in healthy adults. Here, we used this approach to investigate whether there was a systematic pattern of connectivity associated with decision-making performance in patients with focal damage in areas not classically associated with decision-making. These patients were categorized a priori into "impaired" or "unimpaired" groups based on their performance on the Iowa Gambling Task (IGT). Lesion-derived network maps based on the impaired patients showed overlap in somatosensory, motor and insula cortices, to a greater extent than patients who showed unimpaired IGT performance. Akin to the classic concept of "diaschisis" (von Monakow, 1914), this focus on the remote effects that focal damage can have on large-scale distributed brain networks has the potential to inform not only differences in decision-making behavior, but also other cognitive functions or neurological syndromes where a distinct phenotype has eluded neuroanatomical classification and brain-behavior relationships appear highly heterogeneous. PMID- 26994345 TI - Targeted delivery of let-7b to reprogramme tumor-associated macrophages and tumor infiltrating dendritic cells for tumor rejection. AB - Both tumor associated macrophages (TAMs) and tumor infiltrating dendritic cells (TIDCs) are important components in the tumor microenvironment that mediate tumor immunosuppression and promote cancer progression. Targeting these cells and altering their phenotypes may become a new strategy to recover their anti-tumor activities and thereby restore the local immune surveillance against tumor. In this study, we constructed a nucleic acid delivery system for the delivery of let 7b, a synthetic microRNA mimic. Our carrier has an affinity for the mannose receptors on TAMs/TIDCs and is responsive to the low-pH tumor microenvironment. The delivery of let-7b could reactivate TAMs/TIDCs by acting as a TLR-7 agonist and suppressing IL-10 production in vitro. In a breast cancer mouse model, let-7b delivered by this system efficiently reprogrammed the functions of TAMs/TIDCs, reversed the suppressive tumor microenvironment, and inhibited tumor growth. Taken together, this strategy, designed based upon TAMs/TIDCs-targeting delivery and the dual biological functions of let-7b (TLR-7 ligand and IL-10 inhibitor), may provide a new approach for cancer immunotherapy. PMID- 26994346 TI - Family functioning and adolescent alcohol use: A moderated mediation analysis. AB - The primary goals of this longitudinal study were to examine the relationship between family functioning and adolescent alcohol use and to examine whether depressed mood mediates this relationship. An additional goal was to explore whether these relations were moderated by gender. The sample included 1031 high school students from the Mid-Atlantic United States. Participants completed surveys in school during the spring of 2007, 2008, and 2009. Path analysis results indicated that family functioning predicted alcohol use for girls. Moreover, depressed mood mediated this relationship. None of the direct paths between family functioning and adolescent alcohol use were significant for boys. However, similar to girls, depressed mood negatively predicted alcohol use for boys. Taken together, the findings highlight the need for prevention programs targeting adolescent substance use to consider gender-specific trajectories. PMID- 26994347 TI - Trajectories of dating violence: Differences by sexual minority status and gender. AB - The purpose of this study was to examine how sexual minority status (as assessed using both identity and behavior) was associated with trajectories of dating violence. University students from a large Southwestern university completed questions on their sexual minority identity, the gender of their sexual partners, and about experiences of dating violence for six consecutive semesters (N = 1942). Latent growth curve modeling indicated that generally, trajectories of dating violence were stable across study participation. Sexual minority identity was associated with higher initial levels of dating violence at baseline, but also with greater decreases in dating violence across time. These differences were mediated by number of sexual partners. Having same and other-sex sexual partners was associated with higher levels of dating violence at baseline, and persisted in being associated with higher levels over time. No significant gender difference was observed regarding trajectories of dating violence. PMID- 26994348 TI - Cognitive styles and psychological functioning in rural South African school students: Understanding influences for risk and resilience in the face of chronic adversity. AB - Adverse childhood experiences can show lasting effects on physical and mental health. Major questions surround how children overcome adverse circumstances to prevent negative outcomes. A key factor determining resilience is likely to be cognitive interpretation (how children interpret the world around them). The cognitive interpretations of 1025 school children aged 10-12 years in a rural, socioeconomically disadvantaged area of South Africa were examined using the Cognitive Triad Inventory for Children (CTI-C). These were examined in relation to psychological functioning and perceptions of the school environment. Those with more positive cognitive interpretations had better psychological functioning on scales of depression, anxiety, somatization and sequelae of potentially traumatic events. Children with more negative cognitions viewed the school environment more negatively. Children living in poverty in rural South Africa experience considerable adversity and those with negative cognitions are at risk for psychological problems. Targeting children's cognitive interpretations may be a possible area for intervention. PMID- 26994349 TI - Easily separated silver nanoparticle-decorated magnetic graphene oxide: Synthesis and high antibacterial activity. AB - Silver nanoparticle-decorated magnetic graphene oxide (MGO-Ag) was synthesized by doping silver and Fe3O4 nanoparticles on the surface of GO, which was used as an antibacterial agent. MGO-Ag was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Energy dispersive X-ray (EDS), X ray diffraction (XRD), Raman spectroscopy and magnetic property tests. It can be found that magnetic iron oxide nanoparticles and nano-Ag was well dispersed on graphene oxide; and MGO-Ag exhibited excellent antibacterial activity against Escherichia coli and Staphylococcus aureus. Several factors were investigated to study the antibacterial effect of MGO-Ag, such as temperature, time, pH and bacterial concentration. We also found that MGO-Ag maintained high inactivation rates after use six times and can be separated easily after antibacterial process. Moreover, the antibacterial mechanism is discussed and the synergistic effect of GO, Fe3O4 nanoparticles and nano-Ag accounted for high inactivation of MGO-Ag. PMID- 26994351 TI - Controlled uptake and release of imatinib from ultrasound nanoparticles Cu3(BTC)2 metal-organic framework in comparison with bulk structure. AB - The porosity of metal-organic frameworks (MOFs) is an important point concerning the possible use of such functional materials for different purposes. In this work, we study uptake and release properties of imatinib (IM) from nano Cu(II) MOF in comparison with bulk Cu(II)-MOF. To explore the absorption ability of the Cu(II)-MOF to IM, fresh sample of Cu3(BTC)2 was immersed in an aqueous solution of IM and were monitored in real time with UV/vis spectroscopy. Results show that the adsorbed quantity of IM over nano Cu3(BTC)2 (I) is much higher than those over a bulk Cu3(BTC)2 (II). PMID- 26994350 TI - Phosphate effects on cadmium(II) sorption to ferrihydrite. AB - HYPOTHESIS: Phosphate influences the sorption of metals to iron (hydr)oxides. An enhanced formation of inner-sphere complexes on the (hydr)oxide surface can be attributed to electrostatic interactions and/or to changes in metal coordination on the iron (hydr)oxide surface. Phosphate was expected to increase cadmium(II) sorption on ferrihydrite. It should be possible to identify changes in cadmium(II) coordination upon phosphate addition by Extended X-ray absorption fine structure (EXAFS) spectroscopy and implement the identified complexes in a surface complexation model (SCM). EXPERIMENTS: The effect of phosphate addition on cadmium(II) sorption to ferrihydrite was studied by a series of batch experiments covering the pH range from 4 to 8. EXAFS spectroscopy was performed on ferrihydrite from the batch experiments at the cadmium K edge. The identified surface complexes were incorporated in the Charge distribution multisite complexation (CD-MUSIC) model, and new surface complexation constants were optimized. FINDINGS: Without phosphate addition cadmium(II) formed inner-sphere bidentate complexes on the ferrihydrite surface. With phosphate there was an increased cadmium(II) sorption that could not be explained by electrostatic interactions alone. The enhancement was best explained by the formation of a ternary complex including cadmium(II), phosphate and ferrihydrite surface groups. PMID- 26994352 TI - Extraction of model contaminants from solid surfaces by environmentally compatible microemulsions. AB - In the present contribution, we evaluate the efficiency of eco-friendly microemulsions to decontaminate solid surfaces by monitoring the extraction of non-toxic simulants of sulfur mustard out of model surfaces. The extraction process of the non-toxic simulants has been monitored by means of spectroscopic and chromatographic techniques. The kinetics of the removal process was analyzed by different empirical models. Based on the analysis of the kinetics, we can assess the influence of the amounts of oil and water and the microemulsion structure on the extraction process. PMID- 26994354 TI - Effects of solution pH and synthetic method on destabilization process of polytitanium-silicate-chloride. AB - Effect of solution pH on coagulation performance and flock properties of a novel inorganic polymer coagulant-polytitanium-silicate-chloride (PTSC) in humic acid kaolin water treatment was investigated in this work. PTSC was synthesized by two approaches: composite and co-complexion, denoted as PTSCm and PTSCc respectively. The effect of the synthetic method was also considered. Results indicated that turbidity and DOM removal were improved by addition of polysilicic acid, especially under acidic condition. PTSCc achieved slightly better DOM removal than that of PTSCm. Flocks formed under acidic condition was smaller than those form under alkaline condition. In addition, flocks formed by PTSCc were larger than PTSCm flocks. Results also indicated that flock strength and recovery ability was slightly improved by the addition of PSiA. Moreover, under acidic condition, PTSC flocks had larger fractal dimension with more compact structure, especially for PTSCm flocks. In contrast, they were looser compared with PTC flock, especially for PTSCm flocks under neutral and alkaline conditions. PMID- 26994353 TI - Optimisation of immuno-gold nanoparticle complexes for antigen detection. AB - The aim of this investigation was to define the optimum method of binding antibodies to the surface of gold nanoparticles (AuNPs) and then to apply the optimised antibody-functionalised AuNPs for the detection of a target antigen. A detailed investigation of three different techniques for the functionalisation of AuNPs with anti-cocaine antibody and methods for the subsequent characterisation of the antibody-functionalised AuNP are reported. The addition of anti-cocaine antibody onto the AuNP surface was facilitated by either: a polyethylene glycol (PEG) linker with a COOH terminal functional group; an aminated PEG ligand; or an N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP)-Protein A/G intermediate. Characterisation of the functionalised particles was performed using transmission electron microscopy, UV-Visible spectrophotometry and by agarose gel electrophoresis. In addition, the cocaine binding efficacy of the resultant AuNPs and their cocaine-binding capacity was determined using a cocaine-horseradish peroxidase conjugate, and by the application of a microtiter plate-based immunoassay. The results showed that the number of antibody per particle was the highest when the AuNP were functionalised with the Protein A/G intermediate. As compared to free antibody, the cocaine binding efficacy was significantly enhanced using the AuNP-Protein A/G-antibody complex. This optimal antibody antigen binding efficacy is thought to be the result of the large number of antibody per particle and the oriented binding of the antibody to the Protein A/G on the AuNP surface. These results highlight the ideal immuno-gold nanoparticle characteristics for the detection of target antigens such as cocaine. PMID- 26994355 TI - Double-Barrier mechanism for chromium immobilization: A quantitative study of crystallization and leachability. AB - Glass-ceramics are well known for the excellent combination properties provided by their components, a glassy matrix and crystalline phases, and have promising applications in the immobilization and detoxification of solid waste containing toxic metals. Glass-ceramic products were successfully synthesized in CaO-MgO SiO2-Al2O3 -Cr2O3 system. Two key measures--partitioning ratio of Cr in the spinel and Cr leaching ratio--were used to investigate the mechanism of Cr immobilization in the glass-ceramic products. The results of powder X-ray diffraction revealed that both spinel and diopside were major crystalline phases in the products. The value of x in the MgCr(x)Al(2-x)O4 spinel was highly related to the amount of Cr2O3 added to the glass-ceramic system. As Cr2O3 content increased, the proportion of spinel phase increased, while that of glass phase decreased. The partitioning ratio of Cr in spinel phase was about 70% for 2 wt.% Cr2O3, and increased to 90% when loaded with 10 wt.% of Cr2O3. According to the results of the prolonged toxicity characteristic leaching procedure, the Cr leaching ratio decreased with the increase of Cr partitioning ratio into the spinel phase. The findings of this study clearly indicate that glass-ceramic formed by spinel structure and residual glass successfully immobilized Cr. PMID- 26994356 TI - Repeated bouts of fast eccentric contraction produce sciatic nerve damage in rats. AB - INTRODUCTION: We evaluated sciatic nerve impairment after eccentric contractions (ECs) in rat triceps surae. METHODS: Wistar rats were randomly assigned to different joint angular velocity: 180 degrees /s (FAST), 30 degrees /s (SLOW), or nontreated control (CNT). FAST and SLOW groups were subjected to multiple (1-4) bouts of 20 (5 reps, 4 sets) ECs. Nerve conduction velocity (NCV) and isometric tetanic ankle torque were measured 24 h after each ECs bout. We also assessed nerve morphology. RESULTS: After 4 ECs bouts, NCVs and isometric torque in the FAST group were significantly lower than those in the CNT (NCV: 42%, torque: 66%; P < 0.05). After 4 bouts, average nerve diameter was significantly smaller in the FAST group [2.39 +/- 0.20 MUm vs. 2.69 +/- 0.20 MUm (CNT) and 2.93 +/- 0.24 MUm (SLOW); P < 0.05] than that in other two groups. CONCLUSIONS: Chronic ECs with high angular velocity induce serious nerve damage. Muscle Nerve 54: 936-942, 2016. PMID- 26994357 TI - Enacting the molecular imperative: How gene-environment interaction research links bodies and environments in the post-genomic age. AB - Despite a proclaimed shift from 'nature versus nurture' to 'genes and environment' paradigms within biomedical and genomic science, capturing the environment and identifying gene-environment interactions (GEIs) has remained a challenge. What does 'the environment' mean in the post-genomic age? In this paper, we present qualitative data from a study of 33 principal investigators funded by the U.S. National Institutes of Health to conduct etiological research on three complex diseases (cancer, cardiovascular disease and diabetes). We examine their research practices and perspectives on the environment through the concept of molecularization: the social processes and transformations through which phenomena (diseases, identities, pollution, food, racial/ethnic classifications) are re-defined in terms of their molecular components and described in the language of molecular biology. We show how GEI researchers' expansive conceptualizations of the environment ultimately yield to the imperative to molecularize and personalize the environment. They seek to 'go into the body' and re-work the boundaries between bodies and environments. In the process, they create epistemic hinges to facilitate a turn from efforts to understand social and environmental exposures outside the body, to quantifying their effects inside the body. GEI researchers respond to these emergent imperatives with a mixture of excitement, ambivalence and frustration. We reflect on how GEI researchers struggle to make meaning of molecules in their work, and how they grapple with molecularization as a methodological and rhetorical imperative as well as a process transforming biomedical research practices. PMID- 26994358 TI - Global health diplomacy: A critical review of the literature. AB - Global health diplomacy (GHD) describes the practices by which governments and non-state actors attempt to coordinate and orchestrate global policy solutions to improve global health. As an emerging field of practice, there is little academic work that has comprehensively examined and synthesized the theorization of Global Health Diplomacy (GHD), nor looked at why specific health concerns enter into foreign policy discussion and agendas. With the objective of uncovering the driving forces behind and theoretical explanations of GHD, we conducted a critical literature review. We searched three English-language scholarly databases using standardized search terms which yielded 606 articles. After screening of abstracts based on our inclusion/exclusion criteria, we retained 135 articles for importing into NVivo10 and coding. We found a lack of rigorous theorizing about GHD and fragmentation of the GHD literature which is not clearly structured around key issues and their theoretical explanations. To address this lack of theoretical grounding, we link the findings from the GHD literature to how theoretical concepts used in International Relations (IR) have been, and could be invoked in explaining GHD more effectively. To do this, we develop a theoretical taxonomy to explain GHD outcomes based on a popular categorization in IR, identifying three levels of analysis (individual, domestic/national, and global/international) and the driving forces for the integration of health into foreign policy at each level. PMID- 26994359 TI - Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults. AB - BACKGROUND: From birth, the functional properties of the neonatal epidermal barrier mature whereby the stratum corneum (SC) hydrates and the skin surface acidifies. The identification of a thinner infant SC compared with adults suggests underdeveloped mechanisms underlying differentiation and desquamation. OBJECTIVES: To assess the functional properties of the neonatal SC from birth, in conjunction with the quantification of superficial chymotrypsin-like protease activity [kallikrein-7 (KLK-7)] and filaggrin-derived natural moisturizing factors (NMF). METHODS: A total of 115 neonates recruited to the Oil in Baby SkincaRE (OBSeRvE) randomized controlled trial underwent a full evaluation of the SC at birth (< 72 h old) and at 4 weeks of age (n = 39, no oil control group) using minimally invasive instrumentation and methodology. A cohort of 20 unrelated adults was recruited for comparison. RESULTS: At birth NMF levels correlated with SC hydration (r = 0.50) and skin-surface pH (r = -0.54). From birth to 4 weeks, transepidermal water loss (TEWL), superficial KLK-7 activity and filaggrin-derived NMF significantly elevated. Impaired epidermal barrier function at birth (> 75th percentile TEWL) was accompanied by significantly elevated chymotrypsin-like protease activity and reduced levels of NMF. CONCLUSIONS: The biophysical, biological and functional properties of the developing neonatal SC are transitional from birth to 4 weeks of age and differ significantly from adults. The presence of impaired barrier function with elevated protease activity and reduced NMF at birth suggests why certain infants are predisposed to epidermal barrier breakdown and the development of atopic dermatitis. PMID- 26994360 TI - Perceived barriers to recommended dietary adherence in patients with type 2 diabetes in Iran. AB - OBJECTIVE: To identify barriers to recommended dietary adherence in patients with type 2 diabetes. DESIGN: Observational cross-sectional study. SAMPLE: One hundred forty six overweight/obese volunteers with type 2 diabetes, who had previously received dietary advice for at least one year, were recruited from two diabetes clinics in Tabriz, north-west of Iran. MEASUREMENTS: A 24-item questionnaire was designed to assess dietary barriers. The validity and reliability of the questionnaire were assessed by Content Validity Index, Content Validity Ratio and Cronbach's alpha, respectively. An exploratory factor analysis with principal component analysis extraction and varimax rotation was utilized in order to extract the underlying factors of dietary nonadherence. RESULTS: Factor analysis yielded seven barrier factors including: situational barriers/difficulty resisting temptation [percent variance=11.64%], stress-related eating disorder/cost [percent variance=9.11%], difficulty with meal and snack plans [percent variance=8.76%], confusion [percent variance=8.45%], work-related issues [percent variance=7.72%], small portion size [percent variance=6.87%] and lack of palatability/family support [percent variance=6.78%]. These factors explained about 59.4% of the total variance. CONCLUSIONS: Overall, patients with type 2 diabetes perceived some barriers to recommended dietary adherence. In dietary counseling, considering and addressing these barriers will likely be effective in increasing the dietary adherence for patients with type 2 diabetes in Iran. PMID- 26994361 TI - Insomnia in epilepsy is associated with continuing seizures and worse quality of life. AB - PURPOSE: To evaluate how insomnia is associated with seizure control and quality of life in patients with epilepsy. METHODS: Consecutive patients with epilepsy attending clinical visits were surveyed with the Insomnia Severity Index (ISI). Patients had to be treated with at least one anticonvulsant and could not have had documented psychogenic pseudoseizure. The presence or absence of seizures and quality of life (QOLIE-P-10) within the past 4 weeks was recorded. Other variables included demographic and clinical data, sleep-wake timing, the Horne Ostberg Morningness-Eveningness Questionnaire (MEQ), sleepiness (Epworth Sleepiness Scale (ESS), and mood (Center for Epidemiologic Studies Depression Scale, CES-D). RESULTS: 207 patients completed surveys. 43% had clinically significant insomnia, and 51% had at least mild insomnia. 58% were seizure free. Mean ISI scores were significantly worse for those with continuing seizures, and more severe ISI scores correlated strongly with worse QOL. Younger age, shorter duration of epilepsy, use of sedative/hypnotics, medical and sleep comorbidities, delayed sleep timing and chronotype, excessive sleepiness, and depression were all associated with more severe insomnia. Those with unexpected health care visits over the most recent 4 weeks had worse insomnia. After adjustment for these covariates, more severe insomnia remained significantly associated with lack of seizure freedom and with worse QOL. SIGNIFICANCE: Insomnia is common in epilepsy, and is associated with short term poor seizure control and worse QOL. Future studies must evaluate cause-and-effect relationships. Assessment of insomnia may be important in the comprehensive care of epilepsy and may influence control of epileptic seizures. PMID- 26994362 TI - Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis. AB - BACKGROUND: Staphylococcus aureus is increasingly implicated as a possible causal factor in the pathogenesis of atopic dermatitis (AD). However, the reported prevalence rates of skin and nasal colonization in the literature vary widely. OBJECTIVES: This study evaluates the prevalence and odds of skin and nasal colonization with S. aureus in patients with AD. METHODS: A systematic literature search was conducted. Odds ratios (ORs) for colonization in patients vs. controls and the prevalence of colonization in patients were pooled using the random effects model. RESULTS: Overall, 95 observational studies were included, of which 30 had a control group. The Newcastle-Ottawa Scale was used to assess study quality, with the majority of studies being of fair to poor quality. Patients with AD were more likely to be colonized with S. aureus than healthy controls [OR 19.74, 95% confidence interval (CI) 10.88-35.81]. Differences were smaller in nonlesional skin (OR 7.77, 95% CI 3.82-15.82) and in the nose (OR 4.50, 95% CI 3.00-6.75). The pooled prevalence of S. aureus colonization among patients was 70% for lesional skin, 39% for nonlesional skin and 62% for the nose. In lesional skin, meta-regression showed that the prevalence of colonization increased with disease severity. Study heterogeneity should be taken into consideration when interpreting the results. CONCLUSIONS: These results demonstrate the importance of colonization with S. aureus in AD. Further evaluation of the mechanisms by which S. aureus influences inflammation is required in addition to the development of targeted strategies to decrease skin and nasal S. aureus load. PMID- 26994363 TI - Magnetic resonance imaging in a large cohort of facioscapulohumeral muscular dystrophy patients: Pattern refinement and implications for clinical trials. AB - OBJECTIVE: Therapeutic perspectives have brought attention to the development of instruments to accurately evaluate the degree of pathology in patients with facioscapulohumeral muscular dystrophy. We aimed to analyze the type and extent of muscle involvement on magnetic resonance imaging (MRI) in a large cohort of patients representative of the broad clinical spectrum of this disease. METHODS: Pelvic and lower limb muscle MRI scans of 269 symptomatic individuals and 19 nonpenetrant gene carriers were assessed. Comparative analysis of the upper girdle scan in 181 of these subjects was also performed. RESULTS: We found a peculiar susceptibility and resistance of particular muscles. Combined involvement of abdominal and hamstring muscles with iliopsoas sparing is common in facioscapulohumeral muscular dystrophy (67% of the patients). Adductor longus and/or rectus femoris, whose involvement can go clinically undetected, are often typically affected in early disease (69% of patients younger than 45 years). The extent of lesions on lower limb MRI showed a high correlation with overall clinical severity. One-fourth of the nonpenetrant gene carriers showed abnormalities on MRI. Hyperintensities on short-tau inversion recovery sequences, markers of active disease, were found in muscles without signs of fatty replacement in 35% of patients, representing early lesions. INTERPRETATION: Our large-scale cross-sectional data provide preliminary evidence for the usefulness of MRI in clinical trials, and set the baseline for longitudinal studies. Muscle MRI can also be used for distinguishing facioscapulohumeral muscular dystrophy from other myopathies in selected cases. Finally, our results are consistent with a model that configures facioscapulohumeral muscular dystrophy as a "muscle-by muscle" disease. Ann Neurol 2016;79:854-864. PMID- 26994364 TI - New pyridinium-based fluorescent dyes: A comparison of symmetry and side-group effects on G-Quadruplex DNA binding selectivity and application in live cell imaging. AB - A series of C1-, C2-and C3-symmetric pyridinium conjugates with different styrene like side groups were synthesized and were utilized as G-quadruplex selective fluorescent probes. The new compounds were well-characterized. Their selectivity, sensitivity, and stability towards G-quadruplex were studied by fluorescence titration, native PAGE experiments, FRET and circular dichroism (CD) analyses. These new compounds investigated in the fluorescence assays were preferentially bound with G-quadruplex DNA compared with other type of nucleic acids and it is fascinating to realize the effects of molecular symmetry and associated side groups showing unexpectedly great influence on the fluorescent signal enhancement for the discrimination of G-quadruplexes DNA from other nucleic acids. This may correlate with the pocket symmetry and shape of the G-quadruplex DNA inherently. Among the compounds, a C2-symmetric dye (2,6-bis-((E)-2-(1H-indol-3-yl)-vinyl)-1 methylpyridin-1-ium iodide) with indolyl-groups substituted was screened out from the series giving the best selectivity and sensitivity towards G-quadruplexes DNA, particularly telo21, due to its high equilibrium binding constant (K=2.17*10(5)M(-1)). In addition, the limit of detection (LOD) of the dye to determine telo21 DNA in bioassays was found as low as 33nM. The results of the study give insight and certain crucial factors, such as molecular symmetry and the associated side groups, on developing of effective fluorescent dyes for G quadruplex DNA applications including G-quadruplex structure stabilization, biosensing and clinical applications. The compound was also demonstrated as a very selective G-quadruplex fluorescent agent for living cell staining and imaging. PMID- 26994365 TI - An amplified electrochemical proximity immunoassay for the total protein of Nosema bombycis based on the catalytic activity of Fe3O4NPs towards methylene blue. AB - A simple electrochemical proximity immunoassay (ECPA) system for the total protein of Nosema bombycis (TP N.b) detection has been developed on the basis of a new amplification strategy combined with target-induced proximity hybridization. The desirable ECPA system was achieved through following process: firstly, the methylene blue (MB) labeled hairpin DNA (MB-DNA) were immobilized on electrode through Au-S bonding. Then, the antibody labeled complementary single stranded DNA probe (Ab1-S1) hybridized with MB-DNA to open its hairpin structure, which led to the labeled MB far away from electrode surface. After that, the presence of target biomarker (TP N.b) and antibody labeled single-stranded DNA (Ab2-S2) triggered the typical sandwich reaction and proximity hybridization, which resulted in the dissociation of Ab1-S1 from electrode and the transformation of the MB-DNA into a hairpin structure with MB approaching to electrode surface. In consequence, the hairpin-closed MB was electrocatalyzed by the modified magnetic nanoparticles (Fe3O4NPs), leading to an increased and amplified electrochemical signal for the quantitative detection of TP N.b. In the present work, Fe3O4NPs were acted as catalyst to electrocatalyze the reduction of electron mediator MB for signal amplification, which could not only overcome the drawbacks of protein enzyme in electrocatalytic signal amplification but also shorten the interaction distance between catalyst and substance. Under optimal condition, the proposed ECPA system exhibited a wide linear range from 0.001ngmL( 1) to 100ngmL(-)(1) with a detection limit (LOD) of 0.54pgmL(-1). Considering the desirable sensitivity and specificity, as well as the novel and simple features, this signal amplified ECPA system opened an opportunity for quantitative analysis of many other kinds of protein biomarker. PMID- 26994366 TI - Exploring human epileptic activity at the single-neuron level. AB - Today, localization of the seizure focus heavily relies on EEG monitoring (scalp or intracranial). However, current technology enables much finer resolutions. The activity of hundreds of single neurons in the human brain can now be simultaneously explored before, during, and after a seizure or in association with an interictal discharge. This technology opens up new horizons to understanding epilepsy at a completely new level. This review therefore begins with a brief description of the basis of the technology, the microelectrodes, and the setup for their implantation in patients with epilepsy. Using these electrodes, recent studies provide novel insights into both the time domain and firing patterns of epileptic activity of single neurons. In the time domain, seizure-related activity may occur even minutes before seizure onset (in its current, EEG-based definition). Seizure-related neuronal interactions exhibit complex heterogeneous dynamics. In the seizure-onset zone, changes in firing patterns correlate with cell loss; in the penumbra, neurons maintain their spike stereotypy during a seizure. Hence, investigation of the extracellular electrical activity is expected to provide a better understanding of the mechanisms underlying the disease; it may, in the future, serve for a more accurate localization of the seizure focus; and it may also be employed to predict the occurrence of seizures prior to their behavioral manifestation in order to administer automatic therapeutic interventions. PMID- 26994367 TI - Permethrin is a potential thyroid-disrupting chemical: In vivo and in silico envidence. AB - Permethrin (PM), one of the most heavily used synthetic pyrethroids, has the potential to interfere with thyroid hormones in mammals, however, the effect is poorly recognized in aquatic organisms. Herein, embryonic zebrafish were exposed to PM (0, 1, 3 and 10MUg/L) until 72h post-fertilization. We demonstrated that PM readily accumulated in larvae with a preference for cis-PM, inhibited development and increased thyroxine and 3,5,3'-triiodothyronine levels accompanying increase in the transcription of most target genes, i.e., thyroid-stimulating hormone beta, deiodinases, thyroid receptors, involved in the hypothalamic-pituitary thyroid axis. Further Western blot analysis indicated that transthyretin (TTR) protein was significantly increased. Molecular docking analysis and molecular dynamics simulations revealed that PM fits into three hydrophobic binding pocket of TTR, one of the molecular targets of thyroid hormone disrupting chemicals (THDCs), and forms strong van der Waals interactions with six resides of TTR, including Leu8, Leu 101, Leu125, Thr214, Leu218 and Val229, thus altering TTR activity. Both in vivo and in silico studies clearly disclosed that PM potentially disrupts the thyroid endocrine system in fish. This study provides a rapid and cost-effective approach for identifying THDCs and the underlying mechanisms. PMID- 26994368 TI - Transcriptional changes in Crassostrea gigas oyster spat following a parental exposure to the herbicide diuron. AB - The Pacific oyster Crassostrea gigas is the main oyster species produced in the world, and a key coastal economic resource in France. High mortalities affect Pacific oysters since 2008 in France and Europe. Their origins have been attributed to a combination of biotic and abiotic factors, underlining the importance of environment quality. The impact of water pollution has been pointed out and one of the pollutants, the genotoxic herbicide diuron, occurs at high concentrations all along the French coasts. Previous work has revealed that a parental exposure to diuron had a strong impact on hatching rates and offspring development even if spats were not exposed to diuron themselves. In this study, we explored for the first time the transcriptional changes occurring in oyster spats (non exposed) originating from genitors exposed to an environmentally relevant concentration of diuron during gametogenesis using the RNAseq methodology. We identified a transcriptomic remodeling revealing an effect of the herbicide. Different molecular pathways involved in energy production, translation and cell proliferation are particularly disturbed. This analysis revealed modulated candidate genes putatively involved in response to oxidative stress and mitochondrial damage in offspring of genitors exposed to diuron. Complementary measures of the activity of enzymes involved in these latter processes corroborate the results obtained at the transcriptomic level. In addition, our results suggested an increase in energy production and mitotic activity in 5-month-spats from diuron-exposed genitors. These results could correspond to a "catch-up growth" phenomenon allowing the spats from diuron exposed genitors, which displayed a growth delay at 3 months, to gain a normal size when they reach the age of 6 months. These results indicate that exposure to a concentration of diuron that is frequently encountered in the field during the oyster's gametogenesis stage can impact the next generation and may result in fitness disturbance. PMID- 26994369 TI - The mechanisms of detoxification of As(III), dimethylarsinic acid (DMA) and As(V) in the microalga Chlorella vulgaris. AB - The response of Chlorella vulgaris when challenged by As(III), As(V) and dimethylarsinic acid (DMA) was assessed through experiments on adsorption, efflux and speciation of arsenic (reduction, oxidation, methylation and chelation with glutathione/phytochelatin [GSH/PC]). Our study indicates that at high concentrations of phosphate (1.62mM of HPO4(2-)), upon exposure to As(V), cells are able to shift towards methylation of As(V) rather than PC formation. Treatment with As(V) caused a moderate decrease in intracellular pH and a strong increase in the concentration of free thiols (GSH). Passive surface adsorption was found to be negligible for living cells exposed to DMA and As(V). However, adsorption of As(III) was observed to be an active process in C. vulgaris, because it did not show saturation at any of the exposure periods. Chelation of As(III) with GS/PC and to a lesser extent hGS/hPC is a major detoxification mechanism employed by C. vulgaris cells when exposed to As(III). The increase of bound As-GS/PC complexes was found to be strongly related to an increase in concentration of As(III) in media. C. vulgaris cells did not produce any As-GS/PC complex when exposed to As(V). This may indicate that a reduction step is needed for As(V) complexation with GSH/PC. C. vulgaris cells formed DMAS(V)-GS upon exposure to DMA independent of the exposure period. As(III) triggers the formation of arsenic complexes with PC and homophytochelatins (hPC) and their compartmentalisation to vacuoles. A conceptual model was devised to explain the mechanisms involving ABCC1/2 transport. The potential of C. vulgaris to bio remediate arsenic from water appeared to be highly selective and effective without the potential hazard of reducing As(V) to As(III), which is more toxic to humans. PMID- 26994370 TI - Delayed effects of methylmercury on the mitochondria of dopaminergic neurons and developmental toxicity in zebrafish larvae (Danio rerio). AB - Methylmercury (MeHg) is a known neurotoxicant affecting the central nervous system but effects on dopaminergic (DA) neurons are not well understood. Wild type zebrafish (Danio rerio) and two transgenic lines: Tg(dat:eGFP) expressing enhanced green fluorescent protein (eGFP) in DA neuron clusters and Tg(dat:tom20 MLS-mCherry) expressing red fluorescence (mCherry) targeted to mitochondria of DA neurons were used to evaluate the effects of micromolar MeHg exposure on DA neuron and whole animal motor function during early development. Three-day-old larvae were exposed to micromolar concentrations of MeHg (0.03, 0.06, and 0.3MUM) in system water. Exposure to 0.3MUM MeHg caused mortality and significant morphological abnormalities including edema, curvature of the spine, and hemorrhages in zebrafish larvae after a 48h exposure period. At 0.06MUM MeHg, the appearance of morphological abnormalities was delayed for 72h and far less severe, whereas 0.03MUM MeHg did not cause any morphological defects or mortalities. A delayed but significant reduction in locomotor ability and mCherry fluorescence in specific brain regions in the 0.06MUM MeHg exposed larvae suggests that DA neuron function rather than neuron numbers was compromised. Double immunolabeling with tyrosine hydroxylase and pan neural staining showed no effect of MeHg exposure. We have established Tg(dat:tom20 MLS-mCherry) zebrafish larvae as a model which can be used to assess MeHg neurotoxicity and that exposure to low dose MeHg (0.06MUM) during development may predispose DA neurons to impairment caused by changes in mitochondrial dynamics. PMID- 26994371 TI - What drives technology-based distractions? A structural equation model on social psychological factors of technology-based driver distraction engagement. AB - BACKGROUND: With the proliferation of new mobile and in-vehicle technologies, understanding the motivations behind a driver's voluntary engagement with such technologies is crucial from a safety perspective, yet is complex. Previous literature either surveyed a large number of distractions that may be diverse, or too focuses on one particular activity, such as cell phone use. Further, earlier studies about social-psychological factors underlying driver distraction tend to focus on one or two factors in-depth, and those that examine a more comprehensive set of factors are often limited in their analyses methods. OBJECTIVE: The present work considers a wide array of social-psychological factors within a structural equation model to predict their influence on a focused set of technology-based distractions. A better understanding of these facilitators can enhance the design of distraction mitigation strategies. METHOD: We analysed survey responses about three technology-based driver distractions: holding phone conversations, manually interacting with cell phones, and adjusting the settings of in-vehicle technology, as well as responses on five social-psychological factors: attitude, descriptive norm, injunctive norm, technology inclination, and a risk/sensation seeking personality. Using data collected from 525 drivers (ages: 18-80), a structural equation model was built to analyse these social psychological factors as latent variables influencing self-reported engagement in these three technology-based distractions. RESULTS: Self-reported engagement in technology-based distractions was found to be largely influenced by attitudes about the distractions. Personality and social norms also played a significant role, but technology inclination did not. A closer look at two age groups (18-30 and 30+) showed that the effect of social norms, especially of injunctive norm (i.e., perceived approvals), was less prominent in the 30+ age group, while personality remained a significant predictor for the 30+ age group but marginally significant for the younger group. CONCLUSION: Findings from this work provide insights into the social-psychological factors behind intentional engagement in technology-based distractions and in particular suggesting that these factors may be sensitive to demographic differences. PMID- 26994372 TI - Safety-in-numbers: Estimates based on a sample of pedestrian crossings in Norway. AB - Safety-in-numbers denotes the tendency for the risk of accident for each road user to decline as the number of road users increases. Safety-in-numbers implies that a doubling of the number of road users will be associated with less than a doubling of the number of accidents. This paper investigates safety-in-numbers in 239 pedestrian crossings in Oslo and its suburbs. Accident prediction models were fitted by means of negative binomial regression. The models indicate a very strong safety-in-numbers effect. In the final model, the coefficients for traffic volume were 0.05 for motor vehicles, 0.07 for pedestrians and 0.12 for cyclists. The coefficient for motor vehicles implies that the number of accidents is almost independent of the number of motor vehicles. The safety-in-numbers effect found in this paper is stronger than reported in any other study dealing with safety-in numbers. It should be noted that the model explained only 21% of the systematic variation in the number of accidents. It therefore cannot be ruled out that the results are influenced by omitted variable bias. Any such bias would, however, have to be very large to eliminate the safety-in-numbers effect. PMID- 26994373 TI - Risk assessment in ramps for heavy vehicles--A French study. AB - This paper presents the results of a study dealing with the risk for heavy vehicles in ramps. Two approaches are used. On one hand, statistics are applied on several accidents databases to detect if ramps are more risky for heavy vehicles and to define a critical value for longitudinal slope. chi(2) test confirmed the risk in ramps and statistical analysis proved that a longitudinal slope superior to 3.2% represents a higher risk for heavy vehicles. On another hand, numerical simulations allow defining the speed profile in ramps for two types of heavy vehicles (tractor semi-trailer and 2-axles rigid body) and different loads. The simulations showed that heavy vehicles must drive more than 1000 m on ramps to reach their minimum speed. Moreover, when the slope is superior to 3.2%, tractor semi-trailer presents a strong decrease of their speed until 50 km/h. This situation represents a high risk of collision with other road users which drive at 80-90 km/h. Thus, both methods led to the determination of a risky configuration for heavy vehicles: ramps with a length superior to 1000 m and a slope superior to 3.2%. An application of this research work concerns design methods and guidelines. Indeed, this study provides threshold values than can be used by engineers to make mandatory specific planning like a lane for slow vehicles. PMID- 26994374 TI - Spatial regression analysis of traffic crashes in Seoul. AB - Traffic crashes can be spatially correlated events and the analysis of the distribution of traffic crash frequency requires evaluation of parameters that reflect spatial properties and correlation. Typically this spatial aspect of crash data is not used in everyday practice by planning agencies and this contributes to a gap between research and practice. A database of traffic crashes in Seoul, Korea, in 2010 was developed at the traffic analysis zone (TAZ) level with a number of GIS developed spatial variables. Practical spatial models using available software were estimated. The spatial error model was determined to be better than the spatial lag model and an ordinary least squares baseline regression. A geographically weighted regression model provided useful insights about localization of effects. The results found that an increased length of roads with speed limit below 30 km/h and a higher ratio of residents below age of 15 were correlated with lower traffic crash frequency, while a higher ratio of residents who moved to the TAZ, more vehicle-kilometers traveled, and a greater number of access points with speed limit difference between side roads and mainline above 30 km/h all increased the number of traffic crashes. This suggests, for example, that better control or design for merging lower speed roads with higher speed roads is important. A key result is that the length of bus-only center lanes had the largest effect on increasing traffic crashes. This is important as bus-only center lanes with bus stop islands have been increasingly used to improve transit times. Hence the potential negative safety impacts of such systems need to be studied further and mitigated through improved design of pedestrian access to center bus stop islands. PMID- 26994376 TI - Improving global vaccine accessibility. AB - Although the beneficial impact of vaccination is well established, developing countries often rely upon humanitarian support to obtain access to routine immunization schedules. Furthermore, philanthropic funders require that vaccines be supplied at prices that are drastically lower than that charged in developed nations. This pricing requirement arises due to both the massive volume of vaccines needed and the logistics necessary to ensure their integrity (i.e. the cold chain). Cost-prohibitive vaccine formulation strategies, especially for newer vaccines, along with the lack of infrastructure in developing nations can further complicate this process. Extensive research is being conducted to develop novel technological platforms that overcome each of these accessibility impediments. This review provides an overview of the humanitarian organizations and technological developments that are dedicated to improving global healthcare by increasing vaccine accessibility. PMID- 26994375 TI - Clinical features of usual interstitial pneumonia with anti-neutrophil cytoplasmic antibody in comparison with idiopathic pulmonary fibrosis. AB - BACKGROUND AND OBJECTIVE: Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO-ANCA (ANCA/UIP). METHODS: We retrospectively reviewed the medical records of 12 consecutive ANCA/UIP patients not manifesting microscopic polyangiitis and 108 IPF/UIP patients with no autoantibodies, both diagnosed by surgical lung biopsy. RESULTS: There was no significant difference in clinical background, laboratory results and pulmonary function tests between ANCA/UIP patients and IPF/UIP patients except for the percentage of bronchoalveolar lavage neutrophils. HRCT showed subpleural reticulation in both groups. Increased attenuation around honeycombing and cysts was significantly observed in ANCA/UIP. Pathologically, ANCA/UIP had more prominent inflammatory cell infiltration, lymphoid follicles with germinal centres and cellular bronchiolitis. During the disease course, three of 12 patients (25%) developed microscopic polyangiitis. Immunosuppressive treatment tended to be more effective in ANCA/UIP patients, and the survival time in ANCA/UIP patients tended to be longer than those with IPF/UIP. CONCLUSION: ANCA/UIP may be distinguishable from IPF/UIP with a combination of HRCT findings of increased attenuation around honeycombing and cysts and some of the characteristic pathological findings. In contrast to IPF/UIP, immunosuppressive treatment could be a therapeutic option for ANCA/UIP. PMID- 26994378 TI - Epidemiology and risk factors of schizophrenia. AB - Schizophrenia is a severe mental disorder that affects approximately one percent of the general population. The pathogenesis of schizophrenia is influenced by many risk factors, both environmental and genetic. The environmental factors include the date of birth, place of birth and seasonal effects, infectious diseases, complications during pregnancy and delivery, substance abuse and stress. At the present time, in addition to environmental factors, genetic factors are assumed to play a role in the development of the schizophrenia. The heritability of schizo- phrenia is up to 80%. If one parent suffers from the condition, the probability that it will be passed down to the offspring is 13%. If it is present in both parents, the risk is more than 20%. The opinions are varied as to the risk factors affecting the development of schizophrenia. Knowing these factors may greatly contribute to prevention of the condition. PMID- 26994377 TI - Technology development for natural product biosynthesis in Saccharomyces cerevisiae. AB - The explosion of genomic sequence data and the significant advancements in synthetic biology have led to the development of new technologies for natural products discovery and production. Using powerful genetic tools, the yeast Saccharomyces cerevisiae has been engineered as a production host for natural product pathways from bacterial, fungal, and plant species. With an expanding library of characterized genetic parts, biosynthetic pathways can be refactored for optimized expression in yeast. New engineering strategies have enabled the increased production of valuable secondary metabolites by tuning metabolic pathways. Improvements in high-throughput screening methods have facilitated the rapid identification of variants with improved biosynthetic capabilities. In this review, we focus on the molecular tools and engineering strategies that have recently empowered heterologous natural product biosynthesis. PMID- 26994379 TI - Pituitary apoplexy presenting as diabetic ketoacidosis: A great simulator? AB - Pituitary apoplexy is a life-threatening illness due to acute infarction of the pituitary gland. The most common symptoms associated with pituitary apoplexy are headache, nausea, vomiting, visual impairment, hypopituitarism, and altered mental status. Diabetic ketoacidosis is a common acute complication of diabetes mellitus and is itself associated with similar symptoms. We present the case of a 38 year old woman, who presented with altered mental status and biochemical alterations suggestive of diabetic ketoacidosis who was found to have a pituitary apoplexy. The low frequency of this condition coupled with an acute and usually dramatic presentation that includes non-specific symptoms makes it a diagnostic challenge. Pituitary apoplexy can simulate a wide range of neurological conditions. PMID- 26994380 TI - Rare cause of non-healing foot wound--acral lentiginous melanoma. AB - The etiology of skin integrity disorders of the lower extremities can be very diverse. In addition to common diagnoses such as venous ulcers with ischemic etiology, decubitus ulcers and diabetic foot syndrome, ulceration of a malignant etiology must also be considered. Malignant melanoma is one of the most dangerous forms of skin cancer and, although rare, may cause foot lesions. The most frequently encountered type of melanoma on acral parts of the limbs is the rare acral lentiginous variant, which only occurs in 2-10% of all melanoma types. Clinical manifestation ranges from cutaneous surface erosion to ulceration with surrounding hyperkeratosis, which can cause considerable differential diagnostic difficulties in the management of patients with non-healing foot wounds. This paper aims to present a clear case study of a Caucasian female with chronic leg ulceration that resulted in a final diagnosis of malignant acral lentiginous melanoma. Supplemental theoretical information regarding the diagnosis and treatment of malignant melanoma has also been included in the report. Malignant acral lentiginous melanoma is a rare cause of non-healing wounds, but it must be considered in cases with long-term healing complications. Precise diagnostic deliberation is crucial in the management and treatment of all chronic and long term non-healing lesions, and appropriately performed biopsies are essential to determine whether malignancy is the primary cause. PMID- 26994381 TI - Mood improving Potential of a Vitamin Trace Element Composition--A randomized, double blind, placebo controlled clinical study with healthy volunteers. AB - OBJECTIVES: Neurotransmitters regulate mood, attention vigilance and other clinical symptoms linked with depression. Various medications ameliorate symptoms of depression and mood disorders by interference with the serotonic metabolism. Serotonin metabolism depends on nutritional cofactors such as pyridoxin together with essential mineral and trace elements. Both, inflammation and metabolic conditions seem to affect the bioavailability of serotonin crucially. We hypothesized that serotonin supply depends on relevant gastrointestinal precursor absorption and on the availability of nutritive antiinflammatory cofactors. METHODS: We performed a randomized placebo controlled clinical trial in healthy participants to study the bioavailabilty of ingredients of the multivitamin and trace element LaVita' in a prospective randomized placebo controlled double blind trial to establish the mood ameliorating potential. Serotonin and its precursor tryptophan were measured in dry blood samples. Serum parameters like chromium and zinc, as well as vitamin D, vitamin B3 and B6 were determined before intake, and after 3 months and 6 months consumption of the test substances. RESULTS: After 3 months a slight increase of tryptophan (p=0.059) and a significant increase of serum serotonin (p < 0.013) was observed in the verum group. After 6 months the verum group showed a highly significant mean increase in niacin (p < 0.001) and the cofactors of serotonin metabolism pyridoxin (p=0.03), chromium p < 0.01), and zinc (p < 0.001). Serotonin levels droped after 6 months indicating a low risk for overdosing. CONCLUSION: We conclude that a continuous supply with ingredients from the natural source compound LaVita' may contribute to mood improving neurotransmitter activity. PMID- 26994382 TI - Reverse asymmetry and changes in brain structural volume of the basal ganglia in ADHD, developmental changes and the impact of stimulant medications. AB - We discussed the cross section studies and the meta-analysis of published data in children and adolescents with ADHD (both drug naive and receiving stimulant medications), in comparison with healthy children and adolescents of the same age. In children and adolescents with ADHD the deceleration of the maturation dynamics of discrete CNS structures is found, volume reduction and decreased grey matter in prefrontal and occipital regions, which is accompanied by reverse asymmetry of the basal ganglia volume (putamen, nucleus caudate). The above mentioned developmental characteristics are valid only for the ADHD children, who have not been treated by stimulant medications. The stimulant treatment eliminates the mentioned changes into various extend. These developmental changes of CNS structures volume are missing in girls. PMID- 26994383 TI - Prefrontal left--dominant hemisphere--gamma and delta oscillators in general anaesthesia with volatile anaesthetics during open thoracic surgery. AB - OBJECTIVES: The main objective was to indicate sufficient general anaesthesia (GA) inhibition for negative experience rejection in GA. PATIENTS AND METHODS: We investigated the group of patients (n = 17, mean age 63.59 years, 9 male--65.78 years, 8 female - 61.13 years) during GA in open thorax surgery and analyzed EEG signal by power spectrum (pEEG) delta (DR), and gamma rhythms (GR). EEG was performed: OPO - the day before surgery and in surgery phases OP1-OP5 during GA. Particular GA phases: OP1 = after pre- medication, OP2 = surgery onset, OP3 = surgery with one-side lung ventilation, OP4 = end of surgery, both sides ventilation, OP5 = end of GA. pEEG registering in the left frontal region Fp1-A1 montage in 17 right handed persons. RESULTS: Mean DR power in OP2 phase is significantly higher than in phase OP5 and mean DR power in OP3 is higher than in OP5. One-lung ventilation did not change minimal alveolar concentration and gases should not accelerate decrease in mean DR power. Higher mean value of GR power in OPO than in OP3 was statistically significant. Mean GR power in OP3 is statistically significantly lower than in OP4 correlating with the same gases concentration in OP3 and OP4. CONCLUSION: Our results showed DR power decreased since OP2 till the end of GA it means inhibition represented by power DR fluently decreasing is sufficient for GA depth. GR power decay near the working memory could reduce conscious cognition and unpleasant explicit experience in GA. PMID- 26994384 TI - Expression of glial fibrillary acidic protein in astrocytes of rat supraoptic nucleus throughout estrous cycle. AB - OBJECTIVE: Oxytocin (OXT) could facilitate preovulatory luteinizing hormone surge in animals and humans while brain OXT production depends on glial fibrillary acidic protein (GFAP)-associated astrocytic plasticity. Here, we examined if GFAP expressions in OXT-producing hypothalamic supraoptic nucleus (SON) correlate to special estrous stages. METHODS: 38 adult female rats were classified into diestrus, proestrus, estrus, and metestrus groups determined by vaginal smear. Rats were decapitated and the SON was dissected for detecting Fos and GFAP levels by Western Blot and immunohistochemistry. RESULTS: The result showed that Fos expression was significantly high at proestrus compared to other stages in Western blotting. No significant difference in total GFAP expression was observed between rats at different stages of the estrous cycle; however, at proestrus GFAP level at the dorsolateral portion of the SON (a region filled with OXT neurons) was significantly lower than that at the ventro-medial portion in immunohistochemistry. CONCLUSION: There is a functional correlation between supraoptic neuron activity and proestrous OXT peak during estrous cycle; it is likely that a plastic change in GFAP expression in astrocytes selectively occurs around OXT neurons at proestrus and facilitates OXT release. PMID- 26994385 TI - Does Val/Val genotype of GSTP1 enzyme affects susceptibility to colorectal cancer in Saudi Arabia?. AB - OBJECTIVES: Glutathione S-transferase pi (GSTP1) is a candidate enzyme that may be involved in colorectal cancer susceptibility. Polymorphism of GSTP1 gene may cause changes in expression or structure which lead to alteration in the efficiency of catalytic function of the enzyme variants, i.e., deficient detoxification of carcinogens and consequently influences coloreActal cancer development. The present report examined the possible impact of GSTP1 (Ilel05Val) polymorphism and the risk of colorectal cancer. METHODS: Samples of paraffin embedded tissues from 83 patients with colorectal cancer as well as thirty five non-cancerous colon tissues were collected from the archive of the pathology department at King Abdulaziz University in Saudi Arabia. All cancer and control samples were subjects to DNA extraction then amplification. DNA genetic analyzer from Applied Biosystems was used to sequence the product of amplification for genotypes determination. RESULTS: None of the genotypes of GSTP1 was associated with the risk of colorectal cancer development. There were no statistical differences in the frequencies of GSTP1 genotypes between colorectal cancer cases and controls. CONCLUSION: The incidence of (Val/Val) genotype in colorectal cancer cases was three folds higher than controls. This finding is not statistically significant, but it could be of clinical consequence that it may increase the risk of colorectal cancer in Saudi Arabia. PMID- 26994386 TI - Sexual activity during pregnancy. AB - OBJECTIVE: Pregnancy is usually associated with significant regression in genito genital intercourse frequency, sexual desire and satisfaction. The aim of the study was to determine women's sexual habits during the third trimester of gestation and to compare their sexual activity before the current pregnancy and during previous pregnancies in case of multiparas. MATERIAL AND METHODS: The study material consisted of women in the third trimester of pregnancy, recruited from the Outpatient Clinic of the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw between January 2013 and February 2014, who filled out a self-prepared questionnaire. The questionnaire consisted of three parts: demographic data, sexual activity prior to current pregnancy and during gestation, including sexual positions and sources of knowledge regarding the subject. The survey involved 25 questions and was distributed among 220 patients, out of which 165 were returned and 149 properly filled out and analyzed. RESULTS: The average age of the respondents was 29.6 +/- 4.85 years; the majority (78.8%) were in an uncomplicated pregnancy. The decrease in sexual activity was evident in all age groups--the majority usually had sex 1 to 3 times a month in contrast to 1-2 times a week prior to conceiving. Sexual activity decreased significantly with increasing age. The main reasons for abandoning sexual activity included: decreased libido (35.5%), the doctor's suggestion (29%) and fears concerning child's health (29%). During pregnancy the frequency of vaginal intercourse significantly decreased (100% prior to vs. 86.6% during pregnancy; p < 0.001); as did oral sex (44.3% vs. 29.5%; p = 0.043) and anal sex (12% vs. 5.4%; p = 0.02). 54% of the respondents declared reduced satisfaction with sexual life during pregnancy in comparison with the previous period; almost half (43.5%) felt less attractive while pregnant. The same claim was related to libido--it decreased in 58.8% of respondents. Multiparas tended to have sexual intercourses less often in consecutive pregnancies (41.2%) or with an equal frequency (35.3%). The main source of knowledge about sexual life during pregnancy listed by women included internet and other media (63.5%), while medical staff was mentioned by 30%. CONCLUSIONS: Sexual activity decreases during gestation, however, it often result from an increased fear for the child and lack of possibilities to confront and broaden the knowledge on this subject. The role of medical staff in consulting sexual activity problems is insufficient. PMID- 26994387 TI - Effect of venlafaxine on scavenging free radicals in vitro. AB - O BJECTIVE: Venlafaxine (VLF) was examined as a potential donor of H atom(s) to scavenge hydroxyl and peroxy-type radicals generated under aerobic conditions by catalytic oxidation of ascorbate with Cu2+ ions. Kinetics of the electron-donor property of VLF was investigated by standard ABTS and DPPH assays. Electron paramagnetic resonance measurements were applied to prove/disprove the VLF ability to scavenge superoxide anion radical. RESULTS: Results indicated that the drug venlafaxine was slightly capable of donating .H, this way VLF scavenged the in situ generated hydroxyl radicals. Under the experimental conditions VLF was not able to inhibit/retard the propagation of the peroxy-type radicals. Regarding to the drug electron donating property, VLF did not show any ABTS.+ or DPPH. radical quenching property. Venlafaxine was not effective in scavenging O2.-. CONCLUSION: Results of ABTS and DPPH assay showed a negligible redox activity of venlafaxine to both DPPH. and ABTS.+. Venlafaxine was not capable of scavenging the superoxide anion radical generated in KO2/DMSO system, which indicates that VLF is not an efficient electron/proton donor molecule. PMID- 26994388 TI - In children with autoimmune thyroiditis CTLA4 and FCRL3 genes--but not PTPN22- are overexpressed when compared to adults. AB - BACKGROUND: Numerous genetic studies revealed several susceptibility genes of autoimmune thyroid diseases (AITD), including CTLA4, PTPN22 and FCRL3. These immune-modulating genes are involved in genetic background of AITD among children and adult patients. However, possible age-related differences in overexpression of these genes remain unclear. PURPOSE: The goal of this single centre cohort study was evaluation of expression levels of three (3) genes CTLA4, PTPN22 and FCRL3 in adult patients and children with autoimmune thyroiditis. METHODS: A total of 47 patients--24 adults (mean age--47.7 years) and 23 children (mean age- 12.4 years) with autoimmune thyroiditis were assessed for the level of expression of CTLA4, PTPN22 and FCRL3 genes, utilizing ABI PRISM' 7500 Sequence Detection System (Applied Biosystem, Foster City, CA, USA). RESULTS: The overexpression of PTPN22 (mean RQ = 2.988) and FCRL3 (mean RQ = 2.544) genes were confirmed in adult patients with autoimmune thyroiditis, at the same time the expression level of CTLA4 gene was significantly decreased (mean RQ = 0.899) (p < 0.05). Similar discrepancies were not observed in children with autoimmune thyroiditis in whom overexpression of all three genes--CTLA4, PTPN22 and FCRL3--was observed. Differences in CTLA4 and FCRL3 genes expression levels in patients with autoimmune thyroiditis were found depending on the age, with increased expression levels of CTLA4 (mean RQ = 3.45 1) and FCRL3 (mean RQ = 7.410) in children when compared to adults (p < 0.05) (Mann-Whitney's U-test). There were moderate negative linear correlations between two genes in question (CTLA4 and FCRL3) expression level and patients' age [correlation coefficient (r) = -0.529 (p < 0.0002) and -0.423 (p < 0.0032), respectively; Spearman's rank correlation test]. CONCLUSION: Our results are consistent with the hypothesis that there are few age dependent genetic differences as regards autoimmune thyroiditis in adults and children. Accordingly, CTLA4 and FCRL3 genes overexpression may play an important role in children suffering from autoimmune thyroiditis. PMID- 26994389 TI - The dynamics of autonomic nervous system activity and hemodynamic changes in pregnant women. AB - OBJECTIVE: The purpose of this research was to assess the dynamics of autonomic nervous system(ANS) and hemodynamic activity changes during uncomplicated pregnancy. METHODS: We enrolled 36 pregnant women (mean age 29 +/- 4.8 years) and a control group of 10 non-pregnant women (mean age 25.9 +/- 0.88 years). The examination was performed in the 1st, 2nd, and 3rd trimester. Continuous registration of BP, ECG, and cardioimpedance was performed with Task Force Monitor 3040i. ANS activity was measured using the following parameters: HRV, BPV, BRS at rest, and in response to autonomic tests. RESULTS: Compared to the 1st trimester, an increase in HR (73 vs. 92 bpm; p < 0.001) and mean BP (80 vs. 85 mmHg, p < 0.01) was observed in the 3rd trimester. In the 1st trimester, the BRS of pregnant women was insignificantly higher than in the controls (24.8 vs. 22.3 ms/mmHg); subsequently, it decreased significantly, to 13.4 ms/mmHg in the 3rd trimester (p = 0.0004). An increase in nLF (39.57 +/- 13.75 vs. 58.73 +/- 15.55; p = 0.001) and LF/HF ratio (1.03 +/- 0.76 vs. 1.85 +/- 0.8; p < 0.00002) was revealed in HRV analysis conducted in the 3rd trimester, as compared to the 1st tri- mester, along with a decrease in nHF (60.43 +/- 13.71 vs. 41.26 +/- 15.55; p < 0.001). An increase in LF/HF-sBPV (1.05 +/- 0.48 vs. 1.58 +/- 0.44; p = 0.01) was recorded in BPV analysis at rest in the 3rd trimester as compared to the respective 1st trimester value. CONCLUSION: Our findings suggest that pregnancy is associated with dynamic changes in autonomic balance, namely doubled dominance of the sympathetic component. Hypervolemia seems the major factor responsible for autonomic and hemodynamic changes observed during pregnancy, as it causes an increase in BP and simultaneous decrease in BRS. PMID- 26994390 TI - The Polypharmacy Mouse Model: Novel Findings and New Opportunities. PMID- 26994391 TI - Low Hemoglobin Concentrations Are Associated With Sarcopenia, Physical Performance, and Disability in Older Australian Men in Cross-sectional and Longitudinal Analysis: The Concord Health and Ageing in Men Project. AB - BACKGROUND: The objective of this study is to examine associations between Hb levels and sarcopenia, low muscle strength, functional measures, and activities of daily living (ADL) and instrumental ADL (IADL) disabilities in older Australian men. METHODS: Men aged 70 years and older (2005-2007) from the Concord Health and Ageing in Men Project were assessed at baseline (n = 1,705), 2 years (n = 1,367), and 5 years (n = 958). The main outcome measurements were walking speed, muscle strength, ADL and IADL disabilities, and sarcopenia using the Foundation for the National Institutes of Health criteria (low appendicular lean mass adjusted for body mass index < 0.789 and poor grip strength < 26kg). Analysis was performed using Hb levels as a continuous measure, unadjusted and adjusted by age, income, body mass index, measures of health, estimated glomerular function, inflammatory markers, and medication use. Receiver operating characteristic curve analysis was performed to determine a threshold of Hb for each outcome. RESULTS: In cross-sectional and longitudinal analysis, for every 1g/dL increase in Hb, there was a significant reduction in risk of sarcopenia, slow walking speed, poor grip strength, inability to perform chair stands, and ADL and IADL disabilities in unadjusted, age-adjusted, and multivariate-adjusted analysis. The highest value of the Youden Index for Hb was 14.2g/dL for sarcopenia and grip strength, 14.5g/dL for walking speed, and 14.4g/dL for all other outcomes. CONCLUSION: Declines in Hb levels over time are associated with poor functional outcomes. The risks and benefits of interventions to increase Hb among older men warrant further investigation to differentiate whether this is an active contributor to age-related debility or a passive biomarker of it. PMID- 26994392 TI - Is Aesthetic Surgery Safe in the Solid Organ Transplant Patient? An International Survey and Review. AB - BACKGROUND: Improved immunosuppression and lifespans have afforded solid organ transplant (SOT) recipients the opportunity to seek aesthetic surgery. OBJECTIVES: To determine current trends in the provision of aesthetic in the SOT patient population, we polled the international plastic surgery community. We specifically sought to evaluate their experiences with this patient population, as well as to perform a review of the literature to provide updated guidelines for practitioners who may consider performing surgery in the SOT patient population. METHODS: A web-based survey was sent to national and international colleagues to query the experiences and complication rates of performing aesthetic surgery in this patient population. RESULTS: Thirty percent of the 1308 respondents performed surgery in SOT patients. Three hundred and forty practitioners performed 552 procedures with a 4.3% complication rate. Over 68% of all procedures were performed on kidney transplant recipients. CONCLUSIONS: SOT patients can safely undergo elective aesthetic procedures. We recommend working closely with the medical team to assure the best outcomes. PMID- 26994393 TI - Management of Peripheral Entrapment Neuropathy Following Abdominoplasty: A Case Report. PMID- 26994394 TI - Who is Publishing in Facial Cosmetic Surgery? A Citation Analysis Across Specialties Over Five Decades. AB - BACKGROUND: Competition among our sister cosmetic specialties continues to increase. Once a field dominated by plastic surgeons, there is a clear trend toward increased competition from core and non-core disciplines. While these marketplace trends are obvious, how such competition has affected academia or peer reviewed publications is less clear. OBJECTIVES: We analyzed the most cited peer reviewed facial aesthetic literature over the past five decades to see if marketplace trends are echoed in a similar manner across the academic disciplines of plastic surgery, otolaryngology, dermatology, and ophthalmology. METHODS: The top 50 cited articles for each decade from the 1970s to the 2010s were identified for the topics of facelift, rhinoplasty, browlift, and blepharoplasty using the Thomson/Reuters Web of Knowledge. Data collected were: the number of citations/article, first authors' specialty affiliation, and journal specialty affiliation. Data were plotted graphically and trends were analyzed. RESULTS: With regards to first authorship, plastic surgery had the highest percentage across all surgeries at every time point, except for rhinoplasty from 2010 present, when otolaryngology had a higher percentage (48% vs 40%). Observed trends demonstrated: (1) increasing contributions from otolaryngology in rhinoplasty, facelift, and browlift; and (2) increasing contributions from ophthalmology in blepharoplasty. Plastic surgery journals are the most common platform for publication across all four surgeries. CONCLUSIONS: Plastic surgeons, and plastic surgery journals, still remain a strong force in academic facial cosmetic surgery. However, it appears that the competition from non plastic surgeons observed in clinical practice is being mirrored in the area of journal publications. We as a specialty need to continue to strive for high quality academic productivity. PMID- 26994396 TI - What Next in Schizophrenia Genetics for the Psychiatric Genomics Consortium? PMID- 26994395 TI - Prediction of Neurocognitive Deficits by Parkinsonian Motor Impairment in Schizophrenia: A Study in Neuroleptic-Naive Subjects, Unaffected First-Degree Relatives and Healthy Controls From an Indigenous Population. AB - BACKGROUND: Neurocognitive deficits are among the most debilitating and pervasive symptoms of schizophrenia, and are present also in unaffected first-degree relatives. Also, multiple reports reveal parkisonian motor deficits in untreated subjects with schizophrenia and in first-degree relatives of affected subjects. Yet, the relation between motor and cognitive impairment and its value as a classifier of endophenotypes has not been studied. AIMS: To test the efficacy of midbrain hyperechogenicity (MHE) and parkinsonian motor impairment (PKM) as predictors of neurocognitive impairment in subjects with or at risk for schizophrenia, that could be used to segregate them from first-degree relatives and healthy controls. METHOD: Seventy-six subjects with chronic schizophrenia never exposed to antipsychotic medication, 106 unaffected first-degree relatives, and 62 healthy controls were blindly assessed for cognitive and motor function, and transcranial ultrasound. RESULTS: Executive function, fluid intelligence, motor planning, and hand coordination showed group differences. PKM and MHE were significantly higher in untreated schizophrenia and unaffected relatives. Unaffected relatives showed milder impairment, but were different from controls. CONCLUSIONS: PKM and MHE predict cognitive impairment in neuroleptic-naive patients with schizophrenia and their unaffected first-degree relatives and may be used to segregate them from first-degree relatives and healthy controls. PMID- 26994397 TI - Four-Year Follow-up of Cognitive Behavioral Therapy in Persons at Ultra-High Risk for Developing Psychosis: The Dutch Early Detection Intervention Evaluation (EDIE NL) Trial. AB - BACKGROUND: Previously, we demonstrated that cognitive behavior therapy for ultra high risk (called CBTuhr) halved the incidence of psychosis over an 18-month period. Follow-up data from the same study are used to evaluate the longer-term effects at 4 years post-baseline. METHOD: The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients comparing CBTuhr with treatment-as-usual (TAU) for comorbid disorders with TAU only. Of the original 196 patients, 113 consented to a 4-year follow-up (57.7%; CBTuhr = 56 vs TAU = 57). Over the study period, psychosis incidence, remission from UHR status, and the effects of transition to psychosis were evaluated. RESULTS: The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow-up to 12 at 4-year follow-up whereas it did not change in the TAU group (n = 22); this still represents a clinically important (incidence rate ratio [IRR] = 12/22 = 0.55) and significant effect (F(1,5) = 8.09, P = .03), favoring CBTuhr. The odds ratio of CBTuhr compared to TAU was 0.44 (95% CI: 0.24-0.82) and the number needed to treat was 8. Moreover, significantly more patients remitted from their UHR status in the CBTuhr group (76.3%) compared with the TAU group (58.7%) [t(120) = 2.08, P = .04]. Importantly, transition to psychosis was associated with more severe psychopathology and social functioning at 4-year follow-up. CONCLUSIONS: CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still effective at 4-year follow-up. Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and social outcomes compared with non-transitioned cases. TRIAL REGISTRATION: The trial is registered at Current Controlled Trials as trial number ISRCTN21353122 (http://controlled-trials.com/ISRCTN21353122/gaag). PMID- 26994399 TI - Ethiopian agriculture has greater potential for carbon sequestration than previously estimated. AB - More than half of the cultivation-induced carbon loss from agricultural soils could be restored through improved management. To incentivise carbon sequestration, the potential of improved practices needs to be verified. To date, there is sparse empirical evidence of carbon sequestration through improved practices in East-Africa. Here, we show that agroforestry and restrained grazing had a greater stock of soil carbon than their bordering pair-matched controls, but the difference was less obvious with terracing. The controls were treeless cultivated fields for agroforestry, on slopes not terraced for terracing, and permanent pasture for restrained grazing, representing traditionally managed agricultural practices dominant in the case regions. The gain by the improved management depended on the carbon stocks in the control plots. Agroforestry for 6 20 years led to 11.4 Mg ha-1 and restrained grazing for 6-17 years to 9.6 Mg ha-1 greater median soil carbon stock compared with the traditional management. The empirical estimates are higher than previous process-model-based estimates and indicate that Ethiopian agriculture has greater potential to sequester carbon in soil than previously estimated. PMID- 26994398 TI - Shared Etiology of Psychotic Experiences and Depressive Symptoms in Adolescence: A Longitudinal Twin Study. AB - Psychotic disorders and major depression, both typically adult-onset conditions, often co-occur. At younger ages psychotic experiences and depressive symptoms are often reported in the community. We used a genetically sensitive longitudinal design to investigate the relationship between psychotic experiences and depressive symptoms in adolescence. A representative community sample of twins from England and Wales was employed. Self-rated depressive symptoms, paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and parent rated negative symptoms were collected when the twins were age 16 (N = 9618) and again on a representative subsample 9 months later (N = 2873). Direction and aetiology of associations were assessed using genetically informative cross lagged models. Depressive symptoms were moderately correlated with paranoia, hallucinations, and cognitive disorganization. Lower correlations were observed between depression and anhedonia, and depression and parent-rated negative symptoms. Nonsignificant correlations were observed between depression and grandiosity. Largely the same genetic effects influenced depression and paranoia, depression and hallucinations, and depression and cognitive disorganization. Modest overlap in environmental influences also played a role in the associations. Significant bi-directional longitudinal associations were observed between depression and paranoia. Hallucinations and cognitive disorganization during adolescence were found to impact later depression, even after controlling for earlier levels of depression. Our study shows that psychotic experiences and depression, as traits in the community, have a high genetic overlap in mid adolescence. Future research should test the prediction stemming from our longitudinal results, namely that reducing or ameliorating positive and cognitive psychotic experiences in adolescence would decrease later depressive symptoms. PMID- 26994400 TI - Significance of imaging modalities for preoperative evaluation of the pancreaticobiliary system in surgery for pediatric choledochal cyst. AB - OBJECTIVE: Roles of magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), drip infusion cholangiography with computed tomography (DIC-CT), and intraoperative cholangiopancreatography (IOCP) in visualizing pancreaticobiliary anatomy for pediatric choledocal cyst (CC) operations were examined. METHODS: From 1980-2013, 117 pediatric CC patients (median age, 3 years) underwent hepaticojejunostomy at our institution, with imaging modalities of ERCP (n = 81 over 34 years), MRCP, DIC-CT, and IOCP (n = 45, 20, and 45 cases over the last 12 years). First, visualization rates for pancreaticobiliary maljunction (PBM), common bile duct (CBD), pancreatic duct (PD), and intrahepatic bile duct (IHBD) were investigated. Sensitivity, specificity, and accuracy for detecting hepatic duct stricture were then compared between MRCP and IOCP. RESULT: Visualization rates of PBM, CBD, PD, and IHBD were 57%, 100%, 64%, and 100% for MRCP; 82%, 77%, 95%, and 32% for ERCP; 25%, 75%, 21%, and 85% for DIC-CT; and 87%, 100%, 87%, and 100% for IOCP, respectively. Combination of MRCP and IOCP achieved rates of 89%, 100%, 91%, and 100%, respectively. Sensitivity, specificity, and accuracy for detecting stenosis were 86%, 68%, and 71% for MRCP, and 100%, 89%, and 91% for IOCP, respectively. CONCLUSIONS: Combining MRCP and IOCP can provide satisfactory pancreaticobiliary anatomical information for surgical planning for pediatric CC, with hepatic duct strictures evaluated more accurately by IOCP. PMID- 26994401 TI - Emerging roles for motor proteins in progenitor cell behavior and neuronal migration during brain development. AB - Over the past two decades, substantial progress has been made in visualizing and understanding neuronal cell migration and morphogenesis during brain development. Distinct mechanisms have evolved to support migration of the various cell types that compose the developing neocortex. A specific subset of molecular motors, so far consisting of cytoplasmic dynein 1, Kif1a and myosin II, are responsible for cytoskeletal and nuclear transport in these cells. This review focuses on the emerging roles for each of these motor proteins in the migratory mechanisms of neocortical cell types. We discuss how migration can be cell cycle regulated and how coordination of motor activity is required to ensure migratory direction. (c) 2016 Wiley Periodicals, Inc. PMID- 26994402 TI - Effect of systemic bevacizumab in severe hereditary hemorrhagic telangiectasia associated with bleeding. PMID- 26994403 TI - p28 dynein light chains and ciliary motility in Tetrahymena thermophila. AB - Dynein light chains are required for the assembly of axonemal dyneins into cilia and flagella. Most organisms express a single p28 dynein light chain and four to nine one-headed inner arm dynein heavy chains. In contrast, Tetrahymena encodes three p28 dynein light chain genes (p28A, p28B, and p28C) and 18 one-headed inner arm dynein heavy chains. In this article it is shown that mutations in p28A and p28B affected both beat frequency and waveform of cilia, while mutations in p28C affected only ciliary beat frequency. A similar set of dynein heavy chains were affected in both p28AKO and p28BKO, but a distinct set of heavy chains was affected in p28CKO. The results suggested that the p28s have non-redundant functions in Tetrahymena and that p28C was associated with a different set of dynein heavy chains than were p28A and p28B. PMID- 26994404 TI - Distribution patterns of microbial communities in ultramafic landscape: a metagenetic approach highlights the strong relationships between diversity and environmental traits. AB - Microbial species richness and assemblages across ultramafic ecosystems were investigated to assess the relationship between their distributional patterns and environmental traits. The structure of microorganism communities in the Koniambo massif, New Caledonia, was investigated using a metagenetic approach correlated with edaphic and floristic factors. Vegetation cover and soil properties significantly shaped the large phylogenetic distribution of operational taxonomic unit within microbial populations, with a mean per habitat of 3.477 (+/-317) for bacteria and 712 (+/-43) for fungi. Using variance partitioning, we showed that the effect of aboveground vegetation was the most significant descriptor for both bacterial and fungal communities. The floristic significant predictors explained 43% of the variation for both the bacterial and fungal community structures, while the edaphic significant predictors explained only 32% and 31% of these variations, respectively. These results confirm the previous hypothesis that the distribution of microorganisms was more structured by the vegetation cover rather than the edaphic characteristics and that microbial diversity is not limited in ultramafic ecosystems. PMID- 26994405 TI - Intramuscular blood flow quantification with power doppler ultrasonography. AB - INTRODUCTION: Quantification of blood flow to muscle using ultrasound is limited to large vessels. Small vessel intramuscular blood flow cannot be quantified using ultrasound without specialized methods or intravenous contrast. METHODS: We describe a technique using power Doppler to quantify postcontraction hyperemia in intramuscular vessels that can be used at the bedside. RESULTS: In 11 healthy subjects, postcontraction intramuscular blood flow in the forearm flexors and tibialis anterior muscles increased with stronger and repeated contractions. Intravascular blood flow measured by pulsed Doppler in the brachial artery similarly increased. Three patients with muscular dystrophies showed a negligible increase of postcontraction intramuscular blood flow. CONCLUSIONS: Intramuscular blood flow can be quantified using power Doppler ultrasonography; it increases following contraction and may be reduced in patients with muscular dystrophies. This quantitative, noninvasive technique can be applied at the bedside and may facilitate studies of disease impact on intramuscular blood flow. Muscle Nerve 54: 872-878, 2016. PMID- 26994406 TI - Identifying targets of selection in mosaic genomes with machine learning: applications in Anopheles gambiae for detecting sites within locally adapted chromosomal inversions. AB - Chromosomal inversions are important structural changes that may facilitate divergent selection when they capture co-adaptive loci in the face of gene flow. However, identifying selection targets within inversions can be challenging. The high degrees of differentiation between heterokaryotypes, as well as the differences in demographic histories of collinear regions compared with inverted ones, reduce the power of traditional outlier analyses for detecting selected loci. Here, we develop a new approach that uses discriminant functions informed from inversion-specific expectations to classify loci that are under selection (or drift). Analysis of RAD sequencing data we collected in a classic dipteran species with polymorphic inversion clines-Anopheles gambiae, a malaria vector species from sub-Saharan Africa-demonstrates the benefits of the approach compared with traditional outlier analyses. We focus specifically on two polymorphic inversions, the 2La and 2Rb arrangements that predominate in dry habitats and the 2L+(a) and 2R+(b) arrangements in wet habitats, which contrast with the minimal geographic structure of SNPs from collinear regions. With our approach, we identify two strongly selected regions within 2La associated with dry habitat. Moreover, we also show that the prevalence of selection is greater in the arrangement 2L+(a) that is associated with wet habitat (unlike presumed importance of selective divergence associated with the shift of the mosquitoes into dry habitats). We discuss the implications of these results with respect to studies of rapid adaptation in these malaria vectors, and in particular, the insights our newly developed approach offers for identifying not only potential targets of selection, but also the population that has undergone adaptive change. PMID- 26994407 TI - Utility of the revised cardiac risk index for predicting postsurgical morbidity in Hb SC and Hb Sbeta+-thalassemia sickle cell disease. PMID- 26994408 TI - Factors associated with musculoskeletal injuries in children and adolescents with sickle cell disease. PMID- 26994409 TI - Ultrasound assessment of diaphragmatic function in patients with amyotrophic lateral sclerosis. AB - BACKGROUND AND OBJECTIVE: Evaluation of diaphragm function in Amyotrophic Lateral Sclerosis (ALS) is critical in determining when to commence non-invasive mechanical ventilation (NIV). Currently, forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) are volitional measures for this evaluation, but require collaboration and are poorly specific. The primary aim of this study was to assess whether diaphragmatic thickness measured by ultrasound (US) correlates with lung function impairment in ALS patients. The secondary aim was then to compare US diaphragm thickness index (DeltaTdi) with a new parameter (DeltaTmax index). METHODS: 41 patients with ALS and 30 healthy subjects were enrolled in the study. All subjects underwent spirometry, SNIP and diaphragm US evaluation, while arterial blood gases were measured in some patients only. US assessed diaphragm thickness (Tdi) at tidal volume (Vt) or total lung capacity (TLC), and their ratio (DeltaTmax) were recorded. Changes (Delta) in Tdi indices during tidal volume (DeltaTdiVt) and maximal inspiration (DeltaTdiTLC) were also assessed. RESULTS: DeltaTdiTLC (p <0.001) and DeltaTmax (p = 0.007), but not DeltaTdiVt, differed between patients and controls. Significant correlation (p < 0.05) was found between DeltaTdiTLC, DeltaTmax and FVC. The ROC curve analysis for comparison of individual testing showed better accuracy with Deltatmax than with DeltatdiTLC for FVC (AUC 0.76 and 0.27) and SNIP (AUC 0.71 and 0.25). CONCLUSION: Diaphragm thickness assessed by ultrasound significantly correlates with global respiratory alterations in patients with ALS. DeltaTmax represents a new US index of early diaphragmatic dysfunction, better related with the routinely performed lung function tests. PMID- 26994410 TI - Epigenetics in ecology and evolution: what we know and what we need to know. PMID- 26994411 TI - Low- and high-risk human papillomavirus genotype infections in intra-anal warts in HIV-positive men who have sex with men. AB - BACKGROUND: Anogenital warts are often presumed to represent nondysplastic or low grade anal intraepithelial neoplasia (LGAIN). We previously demonstrated that up to 20% of intra-anal warts in HIV-positive men who have sex with men (MSM) contain regions of high-grade AIN (HGAIN). OBJECTIVES: To determine the causative human papillomavirus (HPV) types of low- and high- grade dysplastic areas in warts from HIV-positive MSM. METHODS: A total of 42 intra-anal warts from 41 HIV positive MSM were graded as nondysplastic, LGAIN or HGAIN. Whole-tissue sections (WTS) were analysed with the SPF10 polymerase chain reaction/LiPA25 HPV genotyping system. If the WTS contained multiple HPV types, dysplastic regions were isolated by laser capture microdissection (LCM) for HPV genotyping. RESULTS: Overall, 38 of 42 (91%) WTS tested positive for HPV DNA. Of these, 23 (61%) contained a single HPV type and 15 (39%) contained multiple HPV types. All LCM selected regions contained no more than one HPV type. Ten of 42 (24%) WTS contained HGAIN disease, of which six (60%) were associated with a high-risk HPV (hrHPV) genotype. Twenty-three of 42 WTS contained LGAIN disease, of which two (9%) were associated with hrHPV. AIN lesions containing hrHPV types were identified using p16 staining. CONCLUSIONS: LGAIN lesions can be caused by high risk HPV genotypes and vice versa. We therefore recommend routine follow-up and treatment of all dysplastic intra-anal warts for HIV-positive MSM. PMID- 26994413 TI - An exonic G894T variant of endothelial nitric oxide synthase gene as a risk factor for ischemic stroke in North Indians. AB - Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) enzyme is a critical regulator of cerebrovascular homeostasis. Genetic variability of G894T and intronic 4ab polymorphism in eNOS could affect the expression and activity of eNOS enzyme, modulating NO levels in endothelium. This results in endothelial dysfunction, which can contribute to the pathogenesis of ischemic stroke. The purpose of the study was to evaluate the association of eNOS genetic polymorphisms (G894T and 4ab) with the occurrence of ischemic stroke through various genetic models. Both polymorphisms were genotyped in 120 ischemic stroke patients diagnosed with MRI and other ancillary techniques and 101 control subjects free of neurological abnormalities, using PCR-RFLP technique and direct PCR respectively. The genotypes of both G894T and 4ab variants were found to be in Hardy Weinberg equilibrium for cases and controls. The significant variation was observed in the genotypic and allelic frequencies for G894T polymorphism between cases and controls, indicating the association of G894T variability with ischemic stroke. However, the difference between cases and controls was insignificant for eNOS 4ab polymorphism with regard to genotypic and allelic distribution. Except for recessive model, both dominant (GT/TT vs. GG) and co dominant (TT vs. GT or GT vs. GG) models indicated nearly two-fold and 1.93 increased risk of ischemic stroke for G894T polymorphism, but none of them suggested the influence of eNOS 4ab polymorphism on ischemic stroke susceptibility. Haplotype analysis revealed the higher frequency of GT-4bb genotype combination in cases as compared to controls, but without significant difference. The study concluded that SNP G894T variant is associated with ischemic stroke and might contribute to ischemic stroke susceptibility in North Indians. However, this outcome needs to be confirmed by studies with large sample size. PMID- 26994412 TI - Histopathology of removed indwelling pleural catheters from patients with malignant pleural diseases. AB - BACKGROUND AND OBJECTIVE: Indwelling pleural catheters (IPC), used for management of malignant pleural effusions, are often left in situ for a long duration. This study reports for the first time the histological findings of IPCs removed from patients with underlying pleural malignancy. METHODS: Forty-one IPCs (in situ for median 126 days, interquartile range 43-226) that were removed over a 54-month period from a single centre were examined. RESULTS: Mesothelioma (n = 18) was the predominant underlying malignancy followed by breast, tubo-ovarian and lung carcinomas. The catheter tubing was fully intact macroscopically in all IPCs. There was no evidence of direct tumour invasion or cancer cell growth on the catheter surfaces in none of the 29 IPCs that were histologically examined. Malignant cells were seen within organizing fibrinous tissues in the lumen of 11 IPCs (27%). A foreign body giant cell reaction was present at the cuff site in all the 29 IPC in which the subcutaneous cuff was examined. Acute (n = 10) and/or chronic inflammatory changes were seen in the luminal contents in all 41 IPCs. CONCLUSION: Our study provides reassuring evidence that the IPC material does not support direct tumour growth or invasion even in the setting of high mesothelioma prevalence. See Editorial, page 787. PMID- 26994414 TI - Alteration of spontaneous spectral powers and coherences of local field potential in prenatal valproic acid mouse model of autism. AB - Previously, autism spectrum disorder (ASD) has been identified mainly by social communication deficits and behavioral symptoms. However, a link between behaviors and learning process in the brain of animal model of autism remained largely unexplored. Particularly, spontaneous neural signaling in learning-related brain areas has not been studied. This study investigated local field potential (LFP) of the hippocampus (HP), the olfactory bulb (OB) and the medial prefrontal cortex (mPFC) in mice prenatally exposed to valproic acid (VPA) on gestational day 13. Adult male Swiss albino mouse offspring implanted with intracranial electrodes were used. VPA-exposed mice exhibited ASD-associated behaviors. Hippocampal LFP analysis revealed that VPA group significantly increased low gamma activity (25 45 Hz) during awake immobility. Regression analyses confirmed positive correlations between locomotor speed and hippocampal theta oscillations in control but not VPA group. VPA group exhibited increases in delta (1-4 Hz) and beta (25-35 Hz) activities in OB during awake immobility and active exploring, respectively. Moreover, significantly increased and decreased coherences between HP and OB of VPA animals were seen within gamma (active exploration) and theta (awake immobility) ranges, respectively. In addition, significant increase in coherence between HP and mPFC was seen within delta range during active exploration. In addition to three ASD symptoms, VPA animals also exhibited differential patterns of olfacto-hippocampal LFP, altered locomotor speed-related hippocampal theta activities and distinct interplays between HP and learning related brain areas. The altered olfacto-hippocampal and medial prefrontal cortex hippocampal networks may underlie impairments in autism mouse model. PMID- 26994415 TI - Antidepressant-like and anxiolytic-like effects of mild hypobaric hypoxia in mice: possible involvement of neuropeptide Y. AB - Previous studies have demonstrated that repeated submission of rats to mild hypobaric hypoxia reduces the persistent behavioral and hormonal depressive symptoms induced by exposure to footshock in the learned helplessness paradigm. The aim of this study was to determine whether hypoxic preconditioning of mice can also induce antidepressant- and anxiolytic-like effects that are detectable with the other commonly used behavioral tests, and to determine whether these effects are accompanied by an increase in neuropeptide Y (NPY) in the hippocampus, which may suggest the involvement of NPY in these mechanisms. The intermittent mild hypobaric hypoxia was generated by 2-h exposure of mice to 0.47 atm for 3 consecutive days. In the tail suspension test a significant decrease in the duration of immobility was observed 24 h, but not 48 h after the last hypobaric session. The elevated plus maze trials performed 48 h after preconditioning showed a significant increase in the frequency of open arm entries, a reduction in the duration of closed arm occupancy and substantially more time spent in the open arms in comparison to the control groups. The open field test demonstrated the absence of increases in general activity or unspecific exploratory behavior in hypoxia-preconditioned mice. The EIA test detected a statistically significant but relatively weak increase in the NPY content in the hippocampus 24 h after preconditioning. Together, our data demonstrate that preconditioning of mice with intermittent mild hypobaric hypoxia induces anxiolytic- and antidepressant-like effects. They are accompanied by up regulation of NPY which may suggest its mechanistic role. PMID- 26994416 TI - Effects of perinatal undernutrition on the basilar dendritic arbor of the anterior cingulate pyramidal neurons in lactating dams. AB - In altricial species, early pre- and neonatal undernutrition interferes with the neuronal organization of several brain structures that have critical time windows for synaptic organization, including the prefrontal cortex. In Golgi-Cox stained tissue the basilar dendritic arbor of pyramidal neurons in the anterior cingulate cortex of early underfed adult lactating dams was evaluated. The anterior cingulate of the rat plays a major role in the execution of sexual, maternal and visual attentional control and other cognitive responses. The effects of neonatal undernutrition on the basilar dendritic tree and perikaryon measurements in layer II/III pyramidal neurons of the anterior cingulate were examined in lactating dams at postpartum days 8 and 12. In the underfed dams the distal portions of the basilar dendrites had fewer branches and a lower dendritic density of dendrites, and neurons had perikarya with reduced perimeter and cross-sectional area. Thus, the neuronal alterations may interfere the plastic synaptic activity and with maternal cognitive performance of rats subjected to early underfeeding. These anatomical alterations of the anterior cingulate may help to understand the disruption of long-term cognitive processes associated with perinatal food restriction. PMID- 26994417 TI - Lesions of the central nucleus of the amygdala only impair flavor aversion learning in the absence of olfactory information. AB - The amygdala is considered a crucial brain nucleus in different modalities of aversive conditioning, including flavor aversion learning (FAL). The importance attributed to the amygdala and its subnuclei has frequently depended on the different stimuli and procedures used in FAL tasks. In this study, FAL was impaired only in animals that had lesions in the central nucleus of the amygdala (CeA) area and also had their olfactory bulbs removed. However, this task was learned by neurologically intact animals, bulbectomized animals, and rats with lesions exclusively centered in the CeA area alone. These results suggest that the CeA area may be relevant in gustatory-gut associative learning but not in FAL, in which the olfactory system may counteract the deficit produced in taste visceral convergence. PMID- 26994418 TI - Relationships between typical histopathological hallmarks and the ferritin in the hippocampus from patients with Alzheimer's disease. AB - Oxidative stress is one of the possible mechanisms of neurodegeneration. One of the elements of this mechanism are altered iron homeostasis and changes concerning of iron metabolism regulatory proteins. The primary iron storage protein in cells is ferritin, composed of heavy (H) and light (L) chains. In brain tissue neurons contain mainly ferritin H-chains, whereas glial cells are rich in L-chains. To the best of our knowledge, this is the first study that compares structure of ferritin and histopathological hallmarks in hippocampal tissue affected by the pathological process of Alzheimer's disease (AD). Our data indicate a statistically significant correlation between the concentration of L chains of ferritin, the H/L ratio and the amount of senile plaques in the subiculum, CA1 and CA4 sectors of the hippocampus (p<0.001, p=0.025, p=0.029). A significant correlation was also found between the concentration of L-ferritin and neuronal loss (p=0.0026). These findings indicate an important role of ferritin light chains in neurodegeneration, that is linked to chronic inflammation processes and the associated activation of the microglia rich of L chains. PMID- 26994419 TI - Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions. AB - Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 ug) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells in region specific manner. The study is also revealing the rationale for its clinical use in cognitive impairment and other neurological diseases. PMID- 26994420 TI - Global orientation estimation in noisy conditions. AB - The present paper studies the perceived orientation of line patterns with variable elongation, line length, orientation jitter, and presentation time. It evaluates whether the internal noise and sampling efficiency evaluated by equivalent noise paradigm (Pelli 1981) depend on the spatial configuration and temporal characteristics of the stimulation. The evaluated internal noise was compared to the results of double-pass noise estimation. In addition, the eye movements of the participants during active exploration of the line patterns were recorded and analyzed with respect to the stimulus characteristics. The results indicate the presence of late internal noise and show that the internal noise and sampling efficiency strongly depend on the elongation, duration and line length of the patterns. The response time increases with the orientation jitter and with the variability in line length of the patterns. It is longer also near the reference orientation for the low levels of added external noise. These results contradict some of the major assumptions of the variance-summation model and question its applicability in characterizing the perceived orientation of multi element patterns. PMID- 26994421 TI - Brain-training for physical performance: a study of EEG-neurofeedback and alpha relaxation training in athletes. AB - In recent years, EEG-neurofeedback training (EEG-NFB) has been increasingly used to optimize various brain functions. Better performance in various activities was also reported after relaxation trainings, another popular method in therapeutic practice. Both these methods are used as a part of professional coaching in sports training centers. In the present study, we aimed to evaluate the impact of such holistic training on physiological (EEG) and behavioral measures on semi professional athletes. EEG-NFB paradigm was intended for amplification of the amplitudes of SMR (12-15 Hz) and beta1 (13-20 Hz) bands and simultaneous reduction of the amplitude of theta (4-7.5 Hz) and beta2 (20-30 Hz). Participation in NFB sessions was accompanied with self-administration of relaxing, audio-visual stimulation after each daily athletic training session. The training program resulted in the increase of alpha and beta1 power of trained participants when assessed in rest with eyes-closed. In eyes - open state, participants of the trained group maintained the same level in all frequency bands, in opposite to the control subjects, whose power decreased in the second measurement in beta1 band when compared to the first one. The trained group exhibited greater reduction of reaction times in a test of visual attention than the control group and showed improvement in several performance measures of Kraepelin's work-curve, used to evaluate speed, effectiveness and work accuracy. Together, these results present initial support for the use of holistic, neurophysiological training in sports workout. PMID- 26994422 TI - A mathematical approach for assessing the transport of large neutral amino acids across the blood-brain barrier in man. AB - Changes in the large neutral amino acid (LNAA) transport across the blood-brain barrier (BBB) is thought to contribute to brain dysfunction in a number of clinical conditions, including phenylketonuria, acute liver failure, and sepsis. Here, we present a novel approach for estimating BBB permeability and the LNAA concentrations in brain extracellular fluid, by demonstrating that they can be mathematically derived on the basis of kinetic constants of the BBB available from the literature, if cerebral blood flow and the arterial and jugular venous LNAA concentrations are known. While it is well known that the permeability surface area product of the BBB to a LNAA from blood to brain (PS1) can be calculated from the arterial LNAA concentrations and kinetic constants of the BBB, we demonstrate that the permeability surface area product from brain to blood (PS2) can be calculated by deriving the substrate activity of the saturable transporter from the kinetic constants and arterial and jugular venous LNAA concentrations, and that the concentration of the LNAA in brain extracellular fluid can then be determined. This approach is methodically simple, and may be useful for assessing the transcerebral exchange kinetics of LNAAs in future human experimental and clinical studies. PMID- 26994423 TI - Does the non-genomic effect of testosterone on social anxiety require the presence of a classical steroid receptor? AB - Steroid hormones may act through a rapid mechanism that does not require an intracellular steroid receptor and its effects on gene expression. In this study we have analysed this so-called non-genomic effect of testosterone on social anxiety in rats of both sexes using androgen and oestrogen receptor blockers. Male rats were divided into four groups: SHAM-CTRL (a sham operated group treated with oil as vehicle, n=10), SHAM-TST (a sham operated group treated with testosterone at a dose of 1 mg/kg, n=10), GDX-CTRL (a castrated group treated with oil, n=10) and GDX-TST (a castrated group treated with testosterone at a dose of 1 mg/kg, n=10). Female rats were divided into two groups: OVX-CTRL (an ovariectomized group treated with oil, n=10) and OVX-TST (an ovariectomized group treated with testosterone, n=10). The intracellular androgen receptor was blocked with flutamide and both intracellular oestrogen receptors were blocked with tamoxifen (a selective oestrogen receptor modulator). Rats were tested one hour after oil or testosterone administration in the social interaction test. Although the concentration of testosterone was higher in testosterone groups, no significant difference in social interaction was observed between the groups. In summary, in this first study focusing on the non-genomic effects of testosterone on social interaction no rapid effects of testosterone in adult rats were found. Further studies should analyse potential non-genomic effects of testosterone on other forms of social behaviour. PMID- 26994424 TI - Intra-individual reaction time variability and response preparation: an EEG study. AB - To behave more efficiently the human brain must anticipate future events with different probabilities and prepare appropriate responses. Previous studies demonstrated that participants react faster to more probable stimuli. It has been shown that this effect in reaction time reduction is related to the response preparation process. However it is still unknown what the minimum difference in stimulus probabilities is that is sufficient to elicit response preparation as measured with the EEG. Intra-individual reaction time variability indicates the stability of an individual's response performance and provides useful information about cognitive functioning. It's use has become prevalent in recent clinical studies. In order to extend understanding of cognitive and neural mechanisms of response stability we hypothesized that intra-individual reaction time variability relates to the response preparation process. Specifically, we hypothesized that response preparation to more probable stimuli would result in not only faster reaction time but also in a reduction of response variability. To verify this hypothesis, we tested 14 healthy subjects using reaction time and EEG as dependent measures. Two different stimuli with probabilities of 33.3% and 66.6% were assigned to two counterbalanced responses. The results of our study showed that stimulus probabilities of 66.6% and 33.3% were sufficient to elicit response preparation. Our data also revealed that response preparation to more probable stimuli speeds RT and reduces RT variability. PMID- 26994425 TI - GADD45 proteins inhibit HIV-1 replication through specific suppression of HIV-1 transcription. AB - GADD45 proteins are a group of stress-induced proteins and participate in various cellular pathways including cell cycle regulation, cell survival and death, DNA repair and demethylation. It was recently shown that HIV-1 infection induces the expression of GADD45 proteins. However, the effect of GADD45 on HIV-1 replication has not been studied. Here, we report that overexpression of GADD45 proteins reduces HIV-1 production through suppressing transcription from the HIV-1 LTR promoter. This inhibitory effect is specific to HIV-1, since GADD45 proteins neither inhibit the LTR promoters from other retroviruses nor reduce the production of these viruses. Knockdown of endogenous GADD45 modestly activates HIV-1 in the J-Lat A72 latency cell line, which suggests GADD45 proteins might play a role in maintaining HIV-1 latency. PMID- 26994426 TI - Properties, performance and associated hazards of state-of-the-art durable water repellent (DWR) chemistry for textile finishing. AB - Following the phase-out of long-chain per- and polyfluoroalkyl substances (PFASs), the textile industry had to find alternatives for side-chain fluorinated polymer based durable water repellent (DWR) chemistries that incorporated long perfluoroalkyl side chains. This phase-out and subsequent substitution with alternatives has resulted in a market where both fluorinated and non-fluorinated DWRs are available. These DWR alternatives can be divided into four broad groups that reflect their basic chemistry: side-chain fluorinated polymers, silicones, hydrocarbons and other chemistries (includes dendrimer and inorganic nanoparticle chemistries). In this critical review, the alternative DWRs are assessed with regards to their structural properties and connected performance, loss and degradation processes resulting in diffuse environmental emissions, and hazard profiles for selected emitted substances. Our review shows that there are large differences in performance between the alternative DWRs, most importantly the lack of oil repellence of non-fluorinated alternatives. It also shows that for all alternatives, impurities and/or degradation products of the DWR chemistries are diffusively emitted to the environment. Our hazard ranking suggests that hydrocarbon based DWR is the most environmentally benign, followed by silicone and side-chain fluorinated polymer-based DWR chemistries. Industrial commitments to reduce the levels of impurities in silicone based and side-chain fluorinated polymer based DWR formulations will lower the actual risks. There is a lack of information on the hazards associated with DWRs, in particular for the dendrimer and inorganic nanoparticle chemistries, and these data gaps must be filled. Until environmentally safe alternatives, which provide the required performance, are available our recommendation is to choose DWR chemistry on a case-by-case basis, always weighing the benefits connected to increased performance against the risks to the environment and human health. PMID- 26994427 TI - Vascular endothelium - Gatekeeper of vessel health. AB - The vascular endothelium is an interface between the blood stream and the vessel wall. Changes in this single cell layer of the artery wall are believed of primary importance in the pathogenesis of vascular disease/atherosclerosis. The endothelium responds to humoral, neural and especially hemodynamic stimuli and regulates platelet function, inflammatory responses, vascular smooth muscle cell growth and migration, in addition to modulating vascular tone by synthesizing and releasing vasoactive substances. Compromised endothelial function contributes to the pathogenesis of cardiovascular disease; endothelial 'dysfunction' is associated with risk factors, correlates with disease progression, and predicts cardiovascular events. Therapies for atherosclerosis have been developed, therefore, that are directed towards improving endothelial function. PMID- 26994428 TI - Degradation of lindane and hexachlorobenzene in supercritical carbon dioxide using palladium nanoparticles stabilized in microcellular high-density polyethylene. AB - Palladium nanoparticles stabilized in microcellular high-density polyethylene prepared through supercritical foaming, supercritical impregnation, and H2 reduction are used for the hydrodechlorination of lindane and hexachlorobenzene in supercritical carbon dioxide below 100 degrees C. Both lindane and hexachlorobenzene can be almost 100% transformed to cyclohexane in 1 h. Reaction intermediates, such as lower chlorinated products or benzene, are not observed or exist in trace amount indicating that most of them may undergo reactions without leaving the metal surface. PMID- 26994429 TI - Uptake, translocation and metabolism of decabromodiphenyl ether (BDE-209) in seven aquatic plants. AB - Terrestrial plant uptake of PBDEs from contaminated soils has been widely reported recently. In this study the fate of deca-BDE within a plant/PBDEs/aquatic environment system was investigated through simulated pot experiments. Accumulations of the total PBDEs and deca-BDE were observed in tissues of seven test aquatic plant species, namely Phragmites australis, Cyperus papyrus, Alternanthera philoxeroides, Colocasia esculenta, Scirpus validus, Acorus calamus and Oryza sativa. In all seven plants, O. sativa leads the uptake and accumulation both in the total PBDEs (444.8 ng g(-1)) and deca-BDE (368.0 ng g(-1)) in roots. Among the six common phytoremediation aquatic plants, A. calamus leads the uptake (236.2 ng g(-1)), and P. australis leads the translocation (Cshoot/Croot = 0.35), while A. philoxeroides (43.4%) and P. australis (80.0%) lead in the metabolism efficiencies in the root and shoot, respectively. The detection of seventeen lesser brominated PBDE congeners provided the debromination evidence, and the specific PBDEs profiles in test plant species indicated there is no common metabolic pattern. Furthermore, a relative high proportion of lesser brominated PBDE congeners in shoots suggested the possible metabolic difference between roots and shoots. Finally, a noticeable percentage of penta- and octa-BDE derived from deca-BDE also hint the ecological risk in deca-BDE use. This comparative research on the aquatic plants provide a broad vision on the understanding of plant/PBDEs/aquatic environment interaction system, and may be applied to remediate PBDEs in contaminated waters and sediments. PMID- 26994430 TI - Preliminary validation of a sequential fractionation method to study phosphorus chemistry in a calcareous soil. AB - A sequential fractionation method proposed by Jiang and Gu (1989) distinguished three types of calcium phosphates (Ca-P) according to their different plant availabilities. Three extractants, NaHCO3, NH4Ac, and H2SO4 were used to extract Ca2-P, Ca8-P, and Ca10-P types, respectively, from soil. This sequential fractionation method was tested and modified for analyzing the P chemistry of a calcareous soil. The solubility test and the model diagrams of the stability of the major Ca-P minerals showed that NaHCO3 was able to extract brushite (Ca2-P type), and NH4Ac extracted brushite and beta-tricalcium P (Ca8-P type) as well as hydroxyapatite (Ca10-P type). Therefore the P forms targeted by extraction with NH4Ac should include both Ca8-and Ca10-P types. The sum of the P extracted by all extractants in the sequential fractionation method in the calcareous soil was in agreement with the total P measured by the perchloric acid digestion method. A proportion of organic P measured by the sequential fractionation method was in agreement with the result from solution (31)P NMR spectroscopy. This study showed that the modified sequential fractionation method and its target P forms would be useful for quantifying and characterizing inorganic and organic P in a calcareous soil, even though it should be used in combination with other techniques, such as solution (31)P NMR spectroscopy. PMID- 26994431 TI - Mercury contamination of riverine sediments in the vicinity of a mercury cell chlor-alkali plant in Sagua River, Cuba. AB - Sediment is a great indicator for assessing coastal mercury contamination. The objective of this study was to assess the magnitude of mercury pollution in the sediments of the Sagua River, Cuba, where a mercury-cell chlor-alkali plant has operated since the beginning of the 1980s. Surface sediments and a sediment core were collected in the Sagua River and analyzed for mercury using an Advanced Mercury Analyser (LECO AMA-254). Total mercury concentrations ranged from 0.165 to 97 MUg g(-1) dry weight surface sediments. Enrichment Factor (EF), Index of Geoaccumulation (Igeo) and Sediment Quality Guidelines were applied to calculate the degrees of sediment contamination. The EF showed the significant role of anthropogenic mercury inputs in sediments of the Sagua River. The result also determined that in all stations downstream from the chlor-alkali plant effluents, the mercury concentrations in the sediments were higher than the Probable Effect Levels value, indicating a high potential for adverse biological effects. The Igeo index indicated that the sediments in the Sagua River are evaluated as heavily polluted to extremely contaminated and should be remediated as a hazardous material. This study could provide the latest benchmark of mercury pollution and prove beneficial to future pollution studies in relation to monitoring works in sediments from tropical rivers and estuaries. PMID- 26994432 TI - Effect of bisphenol S exposure on male reproductive system of rats: A histological and biochemical study. AB - Bisphenol S (BPS) has been introduced into the industry as a safer alternative to Bisphenol A. BPS has been detected in human urine sample and induces oxidative stress in vitro and exhibit endocrine disrupting potential in vivo. However, data regarding effect of BPS in mammals is very limited and only a few studies have been carried out. In the present study, direct effect of BPS exposure on oxidative stress and testosterone concentration in rat testis was evaluated in vitro. BPS exposure not only induced oxidative stress but also enhanced antioxidant enzymes activity in the tissue. Based on in vitro results, in vivo study was carried out. In the in vivo sub-chronic study, adult male rats were exposed to different doses of BPS (1-50 MUg/kg day). Significant increase in the testicular reactive oxygen species and lipid peroxidation were observed in the higher doses tested while antioxidant enzymes activity and protein content were significantly reduced. Plasma and intra-testicular testosterone concentrations were reduced in groups treated with higher doses of BPS. Testicular morphology revealed thin seminiferous epithelium in the treated groups as compared to the control. In the epididymis, area of the tubular epithelium showed significant reduction and empty lumen were observed in the groups treated with higher concentrations of BPS. The present data suggest that BPS has the potential to induce oxidative stress in the testis and might have effect on spermatogenesis in rats. PMID- 26994433 TI - Estrogen metabolites in human corpus luteum physiology: differential effects on angiogenic activity. AB - OBJECTIVE: To determine tissue concentrations of E2, estrone, P, and estrogens metabolites (EMs) 2-methoxyestradiol, 2-methoxyestrone, 4-hydroxyestrone, and 16 ketoestradiol in corpus luteum (CL) of different ages, and after hCG administration; and to examine the effects of EMs on vascular endothelial growth factor (VEGF) secretion and angiogenic activity released by cultured luteinizing granulosa cells in the presence and absence of hCG. DESIGN: Experimental study. SETTING: University. PATIENT(S): Thirty-two healthy women of reproductive age. INTERVENTION(S): Corpus luteum was collected at the time of minilaparotomy for tubal sterilization, at varying stages of the luteal phase (LP). Late-LP CL was collected 24 hours after IM administration of 10,000 IU hCG. Granulosa cells were isolated from follicular aspirates obtained from healthy women participating in our IVF program for male factor infertility. MAIN OUTCOMES MEASURE(S): Estrogen metabolite concentrations were determined in CL tissue, and VEGF was assessed in conditioned medium. The angiogenic activity was analyzed by bioassay. RESULT(S): Concentrations of EMs with proangiogenic activity (16-ketoestradiol and 4 hydroxyestrone) were higher in early and mid-LP CL vs. late-LP CL. These EMs and hCG increased VEGF production and angiogenic activity. Conversely, late-LP CL had significantly higher levels of 2-methoxyestrone and 2-methoxyestradiol, which have antiangiogenic activity. Administration of hCG reduced the production of these EMs. CONCLUSION(S): Our findings suggest that the EMs are important paracrine modulators of CL function. Administration of hCG increases the production of EMs with proangiogenic activity and reduces the secretion of those EMs with antiangiogenic action, suggesting a novel mechanism by which the late-LP CL is rescued in conception cycles. PMID- 26994434 TI - Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder - Results from a prospective study. AB - BACKGROUND: Peripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression. AIMS: To investigate whether neutrophins and inflammatory marker vary with mood states and are increased in patients with bipolar disorder type I during euthymia as well as in all affective states as a group, compared to levels in healthy control subjects. METHODS: In a prospective 6-12 months follow-up study, we investigated state specific, intra-individual alterations in levels of BDNF, hsCRP, IL-1beta, IL-6, IL-8, IL-18 and TNF-alpha in 60 patients with bipolar I disorder with an acute severe manic index episode and in subsequent euthymic and depressive and manic states and compared with repeated measurements in healthy control subjects. Data were analysed with linear mixed effects model and with adjustment for gender, age, BMI, alcohol intake and smoking. RESULTS: From inclusion to end of the 6-12 months follow-up, samples of blood were drawn from the 60 patients during a total of 180 affective states, comprising 57 manic, 11 mixed, 23 depressive and 89 states of euthymia. Further, 69 blood samples were drawn from 35 healthy control subjects with three months apart. In unadjusted mixed-model analysis, levels of IL-6 and IL-8 were increased 64% (b=1.64, 95% CI: 1.31-2.05, p=<0.0001) and 24% (b=1.24, 95% CI: 1.05-1.47, p=0.013), respectively in patients with bipolar disorder overall compared with healthy control subjects. However, in adjusted models, no statistically significant differences were found in any measure between patients and control individuals. Levels of hsCRP in depressive states were decreased with 40% (95% CI: 5-62%, p=0.029) compared with euthymia and with 48% (95% CI: 17-66%, p=0.006) when compared with hypomanic/manic states after adjustment. BDNF and the other inflammatory markers did not vary according to affective state in adjusted mixed models. LIMITATIONS: Patients were all medicated, specifically with high doses of atypical antipsychotics during the manic index episodes. CONCLUSIONS: In a sample recruited during hospitalization for acute mania, levels of hsCRP varied according to affective state with higher levels during manic states compared with depressive states. PMID- 26994435 TI - The timing of general population and patient suicide in England, 1997-2012. AB - BACKGROUND: There have been conflicting findings on temporal variation in suicide risk and few have examined the phenomenon in clinical populations. The study investigated seasonal and other temporal patterns using national data. METHODS: Data on 73,591 general population and 19,318 patient suicide deaths in England between 1997 and 2012 were collected through the National Confidential Inquiry into Suicide examining suicide rates in relation to month of the year, day of the week, and individual days of national or religious significance. RESULTS: Suicide incidence fell over successive months of the year and there was evidence of an overall spring peak. Monday was associated with the highest suicide rates and in the patient population this effect appeared to be more pronounced in those aged over 50 or those who lived alone. Suicide risk was significantly lower during Christmas, particularly for women. There was a peak in suicide on New Year's Day in the general population. Other 'special days' were not associated with a change in suicide incidence. LIMITATIONS: We were limited to identifying associations between the variables investigated and were unable to explore causal mechanisms. We did not carry out comprehensive multi-variable adjustment in our regression models. CONCLUSIONS: There is substantial seasonal and temporal variation in suicide deaths, and there appears to be some evidence in the clinical as well as the general population in England. Clinical services should be aware of the risk of suicide just after the weekend, especially in people who live alone, and the potential need for closer supervision during this period. PMID- 26994436 TI - Clinical management following self-harm in a UK-wide primary care cohort. AB - BACKGROUND: Little is known about the clinical management of patients in primary care following self-harm. METHODS: A descriptive cohort study using data from 684 UK general practices that contributed to the Clinical Practice Research Datalink (CPRD) during 2001-2013. We identified 49,970 patients with a self-harm episode, 41,500 of whom had one complete year of follow-up. RESULTS: Among those with complete follow-up, 26,065 (62.8%, 62.3-63.3) were prescribed psychotropic medication and 6318 (15.2%, 14.9-15.6) were referred to mental health services; 4105 (9.9%, CI 9.6-10.2) were medicated without an antecedent psychiatric diagnosis or referral, and 4,506 (10.9%, CI 10.6-11.2) had a diagnosis but were not subsequently medicated or referred. Patients registered at practices in the most deprived localities were 27.1% (CI 21.5-32.2) less likely to be referred than those in the least deprived. Despite a specifically flagged NICE 'Do not do' recommendation in 2011 against prescribing tricyclic antidepressants following self-harm because of their potentially lethal toxicity in overdose, 8.8% (CI 7.8 9.8) of individuals were issued a prescription in the subsequent year. The percentage prescribed Citalopram, an SSRI antidepressant with higher toxicity in overdose, fell sharply during 2012/2013 in the aftermath of a Medicines and Healthcare products Regulatory Agency (MHRA) safety alert issued in 2011. CONCLUSIONS: A relatively small percentage of these vulnerable patients are referred to mental health services, and reduced likelihood of referral in more deprived localities reflects a marked health inequality. National clinical guidelines have not yet been effective in reducing rates of tricyclic antidepressant prescribing for this high-risk group. PMID- 26994437 TI - Comparative effectiveness of long-acting injectable risperidone vs. long-acting injectable first-generation antipsychotics in bipolar disorder. AB - OBJECTIVE: The aim of this study was to compare the treatment effectiveness between long-acting injectable risperidone and long-acting injectable first generation antipsychotics among patients with bipolar disorder. METHOD: We conducted a retrospective cohort study using Taiwan's National Health Insurance Research Database. Patients with bipolar disorder aged 15 years or higher, who were newly administered long-acting injectable antipsychotics between June 1, 2004 and December 31, 2011 were included. The clinical outcome indexes were hospitalization for any mood, manic/mixed, or depressive episodes. In addition, the all-cause discontinuation of long-acting injectable antipsychotic treatment was also assessed. RESULTS: A total of 3916 patients with bipolar disorder were extracted. Compared with risperidone, the use of first-generation antipsychotics was associated with a higher rate of hospitalization for any mood episode and major depressive episode. However, there was no statistically significant difference in treatment discontinuation rate between risperidone and first generation antipsychotics. LIMITATIONS: Information for the severity of mood symptoms, social support, life style, neurological and metabolic adverse effect was not available in this database. In addition, we only measured severe mood episodes with hospitalization as our outcome index. It may not be possible to generalize our findings to mild mood episodes. CONCLUSIONS: Our findings suggested that patients treated with long-acting injectable risperidone might be superior to first-generation antipsychotics in the rate of psychiatric hospitalization. PMID- 26994438 TI - Associations of temporal and energetic characteristics of behavior with depressive symptoms: A population-based longitudinal study within Strelau's Regulative Theory of Temperament. AB - BACKGROUND: Individual dispositions have previously been associated with increased risk for depressive symptoms. The direction of the association has been found to be sometimes reciprocal. We examined whether temperament traits are associated with depressive symptoms and whether depressive symptoms contribute to changes in temperament. METHODS: Participants (n=674-811) were from a population based Young Finns Study. Temperament was assessed by a Finnish version of the Formal Characteristics of Behavior - Temperament Inventory. Depressive symptoms were assessed with modified BDI (mBDI) in 1997, 2001, 2007 and 2012, and BDI-II in 2012. RESULTS: Higher perseveration and emotional reactivity were associated with higher level of depressive symptoms, and higher endurance was associated with lower level of depressive symptoms in 2007 and 2012. These associations were independent of several potential confounders and baseline depressive symptoms. The results of cross-lagged structural equation modeling showed that the associations between temperament and depressive symptoms were reciprocal: briskness, endurance and activity decreased the risk for depressive symptoms while depressive symptoms decreased the level of these characteristics. Perseveration, emotional reactivity and depressive symptoms reinforced each other over time. LIMITATIONS: The depressive symptoms scales we used are not meant for measuring clinically diagnosed depression. The relationships between temperament traits and depressive symptoms were not strong enough to provide a clinical basis for guiding treatment. CONCLUSIONS: Lower perseveration, lower emotional reactivity and higher endurance seem to be health protective temperament characteristics that reduce the risk for depressive symptoms. The reciprocal associations between temperament and depressive symptoms imply mutual health protective and health declining effects. Clinical relevance of the study is that enhancing positive loops and self-concept, and supporting individual stress management might be helpful in prevention of depressive symptoms. PMID- 26994440 TI - Declining trends in injuries and ambulance calls for road traffic crashes in Bahrain post new traffic laws of 2015. AB - Road traffic crashes (RTC) are of serious global health concern. To identify whether the number of ambulance calls, injuries, and deaths has declined after the implementation of the new traffic law (NTL) 2015 in Bahrain, de-identified administrative RTC data obtained from the tertiary care center, and the General Directorate of Traffic (GDT) of Bahrain were used. A quasi-experimental design was employed to trend the impact of the NTL on RTC and associated healthcare events. Bahrainis and non-Bahrainis who met with RTC, either in a vehicle or as a pedestrian, between February 8 and May 8 in 2013, 2014 (pre NTL), and 2015 (post NTL) were included in the study. Our results show a reduction in the number of ambulance calls from vehicular and pedestrian RTC victims. The ambulance calls from pedestrian RTC victims were <10% compared to the number of ambulance calls from vehicular RTC victims. There was a significant reduction in minor injuries post 2015, whereas no obvious difference was seen for serious injuries and deaths. A longer follow-up study to confirm the sustained decline in RTC, enforcing a zero tolerance policy toward traffic transgressions, and raising public awareness on the "critical four minutes" and "golden hour" is recommended. PMID- 26994441 TI - The inhibitory effects of nifedipine on outward voltage-gated potassium currents in mouse neuroblastoma N2A cells. AB - BACKGROUND: Voltage-gated K(+) (Kv) channels have a pivotal role in tuning the action potential duration and excitability in neuronal cells. Although Ca(2+) channel antagonist nifedipine exhibited an inhibitory effect on cardiac Kv currents, a possible action of nifedipine on neuronal Kv currents has not been fully investigated. METHODS: The effects of nifedipine on elicited Kv currents were characterized using whole-cell recording in mouse neuroblastoma N2A cells. RESULTS: Exposure to nifedipine induced a dose-dependent inhibition of Kv currents with an IC50 value of 22.3+/-4.2MUM and prolonged the time course of activation. The half-maximum activation potential was 1.6+/-1.7mV in control conditions and became 13.5+/-1.5mV in 50MUM nifedipine. In addition, the decay rate of Kv currents was substantially accelerated by 39.5% at +60mV. For the voltage-dependent inactivation, the half-maximum inactivation potential was 13.8+/-0.8mV and strongly shifted to the left following treatment with 50MUM nifedipine. CONCLUSION: Treatment with nifedipine exerted a strong influence on the activation and inactivation rate of Kv currents as well as an obvious leftward shift in the inactivation curve. These data indicated that nifedipine exerted an inhibitory effect on Kv currents in N2A cells. PMID- 26994442 TI - A polymorphism in the MSH3 mismatch repair gene is associated with the levels of somatic instability of the expanded CTG repeat in the blood DNA of myotonic dystrophy type 1 patients. AB - Somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 is age dependent, tissue-specific and expansion-biased, contributing toward the tissue specificity and progressive nature of the symptoms. Previously, using regression modelling of repeat instability we showed that variation in the rate of somatic expansion in blood DNA contributes toward variation in age of onset, directly implicating somatic expansion in the disease pathway. Here, we confirm these results using a larger more genetically homogenous Costa Rican DM1 cohort (p<0.001). Interestingly, we also provide evidence that supports subtle sex dependent differences in repeat length-dependent age at onset and somatic mutational dynamics. Previously, we demonstrated that variation in the rate of somatic expansion was a heritable quantitative trait. Given the important role that DNA mismatch repair genes play in mediating expansions in mouse models, we tested for modifier gene effects with 13 DNA mismatch gene polymorphisms (one each in MSH2, PMS2, MSH6 and MLH1; and nine in MSH3). After correcting for allele length and age effects, we identified three polymorphisms in MSH3 that were associated with variation in somatic instability: Rs26279 (p=0.003); Rs1677658 (p=0.009); and Rs10168 (p=0.031). However, only the association with Rs26279 remained significant after multiple testing correction. Although we revealed a statistically significant association between Rs26279 and somatic instability, we did not detect an association with the age at onset. Individuals with the A/A genotype for Rs26279 tended to show a greater propensity to expand the CTG repeat than other genotypes. Interestingly, this SNP results in an amino acid change in the critical ATPase domain of MSH3 and is potentially functionally dimorphic. These data suggest that MSH3 is a key player in generating somatic variation in DM1 patients and further highlight MSH3 as a potential therapeutic target. PMID- 26994444 TI - Bis-GMA affects craniofacial development in zebrafish embryos (Danio rerio). AB - Estrogen is a steroid hormone that is vital in vertebrate development and plays a role in a variety of developmental processes including cartilage and craniofacial formation. The effects of estrogen can be mimicked by other compounds found in the environment known as xenoestrogens. Bisphenol-A (BPA) is a known xenoestrogen and is combined with glycidyl methacrylate to make Bisphenol A glycidyl methacrylate (Bis-GMA), a major component in dental resin based composites (RBCs). Bis-GMA based RBCs can release their components into the saliva and bloodstream. Exposure to 1MUM and 10MUM Bis-GMA in Danio rerio embryos results in increased mortality of approximately 30% and 45% respectively. Changes to gross morphology, specifically craniofacial abnormalities, were seen at concentrations as low as 10nM. While the molecular pathways of Bis-GMA effects have not been studied extensively, more is known about one of the components, BPA. Further research of Bis-GMA could lead to a better understanding of xenoestrogenic activity resulting in improved public and environmental health. PMID- 26994443 TI - The role of HERC2 and RNF8 ubiquitin E3 ligases in the promotion of translesion DNA synthesis in the chicken DT40 cell line. AB - The replicative DNA polymerases are generally blocked by template DNA damage. The resulting replication arrest can be released by one of two post-replication repair (PRR) pathways, translesion DNA synthesis (TLS) and template switching by homologous recombination (HR). The HERC2 ubiquitin ligase plays a role in homologous recombination by facilitating the assembly of the Ubc13 ubiquitin conjugating enzyme with the RNF8 ubiquitin ligase. To explore the role of HERC2 and RNF8 in PRR, we examined immunoglobulin diversification in chicken DT40 cells deficient in HERC2 and RNF8. Unexpectedly, the HERC2(-/-) and RNF8(-/-) cells and HERC2(-/-)/RNF8(-/-) double mutant cells exhibit a significant reduction in the rate of immunoglobulin (Ig) hypermutation, compared to wild-type cells. Further, the HERC2(-/-) and RNF8(-/-) mutants exhibit defective maintenance of replication fork progression immediately after exposure to UV while retaining proficient post replicative gap filling. These mutants are both proficient in mono-ubiquitination of PCNA. Taken together, these results suggest that HERC2 and RNF8 promote TLS past abasic sites and UV-lesions at or very close to stalled replication forks. PMID- 26994445 TI - Transcriptome based identification and tissue expression profiles of chemosensory genes in Blattella germanica (Blattaria: Blattidae). AB - Blattalla germanica is one of the most notorious household insect pests, and evolutionally more primitive than those well studied moths and flies, regarding the molecular mechanisms of chemosensation. In this study, we sequenced, for the first time, the antennal transcriptome of B. germanica using the Illumina HiSeqTM 2000 platform and then conducted the bioinformatic analysis of the data. In total, we identified 73 putative chemosensory genes, with 62 genes being novel in this species. These chemosensory genes included 48 odorant binding proteins (OBPs), 9 chemosensory proteins (CSPs), 6 sensory neuron membrane proteins (SNMPs), 5 odorant receptors (ORs) and 5 ionotropic receptors (IRs). Notably, Plus-C OBPs account for an exceptionally high proportion (39.58%) of the total 48 OBPs in this primitive insect. To predict the chemosensory functions of the genes, a detailed global tissue expression profiling was investigated by reverse transcription polymerase chain reaction (RT-PCR). Most OBP genes showed a chemosensory tissue biased profile, while CSP transcripts were widely and evenly expressed in different tissues. Furthermore, we found that more than half the chemosensory genes were expressed in the cerci, implying the important chemosensory functions of the organ in B. germanica. Taken together, our study provides important bases for elucidation of the molecular mechanisms and evolution of insect chemosensation, and for development of the chemosensation based techniques to control B. germanica. PMID- 26994446 TI - Estimation of time since death by vitreous humor hypoxanthine, potassium, and ambient temperature. AB - Measurement of vitreous humor potassium (K(+)) has since the 1960s been recognized as an adjunct for estimation of time since death. In 1991 we introduced hypoxanthine (Hx) as a new marker. Furthermore we demonstrated that time since death estimation was more accurate when ambient temperature was included in the calculations, both for K(+) and for Hx. In this paper we present a refined method. The subjects consist of 132 cases with known time of death and ambient temperature. One sample from each subject was used in the calculations. Vitreous humor Hx levels were available in all subjects, while K(+) was measured in 106 of the subjects, due to insufficient volume of vitreous humor. Linear regression analysis was applied to model the correlation between vitreous humor Hx and K(+), taking the interactions with temperature into consideration. The diagrams published in 1991, which also included ambient temperature, estimated median time since death with range between the 10th and 90th percentile, whereas the linear regression analysis presented in this paper estimates mean time since death with a corresponding 95% interval of confidence. We conclude that time since death may be estimated with relatively high precision applying vitreous humor Hx and K(+) concentrations combined with ambient temperature. PMID- 26994447 TI - Rapid detection of generalized anxiety disorder and major depression in epilepsy: Validation of the GAD-7 as a complementary tool to the NDDI-E in a French sample. AB - OBJECTIVE: Generalized anxiety disorder (GAD) in people with epilepsy (PWE) is underdiagnosed and undertreated. The GAD-7 is a screening questionnaire to detect GAD. However, the usefulness of the GAD-7 as a screening tool in PWE remains to be validated. Thus, we aimed to: (1) validate the GAD-7 in French PWE and (2) assess its complementarity with regard to the previously validated screening tool for depression, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). METHODS: This study was performed under the auspices of the ILAE Commission on Neuropsychiatry. People with epilepsy >18 years of age were recruited from the specialist epilepsy unit in Marseille, France. The Mini International Neuropsychiatric Interview (MINI) was performed as gold standard, and the Penn State Worry Questionnaire (PSWQ) and the NDDI-E were performed for external validity. Data were compared between PWE with/without GAD using Chi(2) test and Student's t-test. Internal structural validity, external validity, and receiver operator characteristics were analyzed. A principal component factor analysis with Varimax rotation was performed on the 13 items of the GAD-7 (7 items) plus the NDDI-E (6 items). RESULTS: Testing was performed on 145 PWE: mean age = 39.38 years old (SD=14.01, range: 18-75); 63.4% (92) women; 75.9% with focal epilepsy. Using the MINI, 49 (33.8%) patients had current GAD. Cronbach's alpha coefficient was 0.898, indicating satisfactory internal consistency. Correlation between GAD-7 and the PSQW scores was high (r (145)=.549, P<.0001), indicating good external validity. Factor analysis shows that the anxiety investigated with the GAD-7 and depression investigated with the NDDI-E reflect distinct factors. Receiver operator characteristic analysis showed area under the curve of 0.899 (95% CI 0.838-0.943, P < 0.0001) indicating good capacity of the GAD-7 to detect GAD (defined by MINI). Cutoff for maximal sensitivity and specificity was 7. Mean GAD-7 score in PWE with GAD was 13.22 (SD = 3.99), and that without GAD was 5.17 (SD = 4.66). SIGNIFICANCE: This study validates the French language version of the GAD-7 screening tool for generalized anxiety in PWE, with a cutoff score of 7/21 for GAD, and also confirms that the GAD-7 is a short and easily administered test. Factor analysis shows that the GAD-7 (screening for generalized anxiety disorder) and the NDDI-E (screening for major depression) provide complementary information. The routine use of both GAD-7 and NDDI-E should be considered in clinical evaluation of patients with epilepsy. PMID- 26994448 TI - CD4+CD25+ regulatory T cells in tumor immunity. AB - Regulatory T cells (Tregs) are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Depletion of Tregs results in the onset of a variety of autoimmune diseases. Tregs are defined based on expression of CD4, CD25, and the transcription factor, FoxP3. It is now clear that three inhibitory cytokines, IL-10, IL-35 and TGF beta, are key mediators of Tregs function. Tregs have been shown to be important contributors to the development of immune tolerance toward tumors and play a critical role in the induction of tolerance to tumor associated antigens and suppression of anti-tumor immunity. Increasing researches support the existence of elevated numbers of regulatory T cells in cancer patients. Poor prognosis and decreased survival rates are closely correlated with higher Treg cell frequencies. Depletion of Tregs or blockade of their immune inhibitory role can enhance anti-tumor effects. Recent evidence suggests that Tregs may be responsible for the failure of host anti-tumor immunity by suppressing cytotoxic T-cells. In this review, we discuss cellular and molecular mechanisms in the differentiation and function of Tregs in tumor immunity. PMID- 26994449 TI - Uncertainty quantification for discrimination of nuclear events as violations of the comprehensive nuclear-test-ban treaty. AB - Enforcement of the Comprehensive Nuclear Test Ban Treaty (CTBT) will involve monitoring for radiologic indicators of underground nuclear explosions (UNEs). A UNE produces a variety of radioisotopes which then decay through connected radionuclide chains. A particular species of interest is xenon, namely the four isotopes (131m)Xe, (133m)Xe, (133)Xe, and (135)Xe. Due to their half lives, some of these isotopes can exist in the subsurface for more than 100 days. This convenient timescale, combined with modern detection capabilities, makes the xenon family a desirable candidate for UNE detection. Ratios of these isotopes as a function of time have been studied in the past for distinguishing nuclear explosions from civilian nuclear applications. However, the initial yields from UNEs have been treated as fixed values. In reality, these independent yields are uncertain to a large degree. This study quantifies the uncertainty in xenon ratios as a result of these uncertain initial conditions to better bound the values that xenon ratios can assume. We have successfully used a combination of analytical and sampling based statistical methods to reliably bound xenon isotopic ratios. We have also conducted a sensitivity analysis and found that xenon isotopic ratios are primarily sensitive to only a few of many uncertain initial conditions. PMID- 26994450 TI - Excessive crying in infants. AB - OBJECTIVE: Review the literature on excessive crying in young infants, also known as infantile colic, and its effects on family dynamics, its pathophysiology, and new treatment interventions. DATA SOURCE: The literature review was carried out in the Medline, PsycINFO, LILACS, SciELO, and Cochrane Library databases, using the terms "excessive crying," and "infantile colic," as well technical books and technical reports on child development, selecting the most relevant articles on the subject, with emphasis on recent literature published in the last five years. SUMMARY OF THE FINDINGS: Excessive crying is a common symptom in the first 3 months of life and leads to approximately 20% of pediatric consultations. Different prevalence rates of excessive crying have been reported, ranging from 14% to approximately 30% in infants up to 3 months of age. There is evidence linking excessive crying early in life with adaptive problems in the preschool period, as well as with early weaning, maternal anxiety and depression, attention deficit hyperactivity disorder, and other behavioral problems. Several pathophysiological mechanisms can explain these symptoms, such as circadian rhythm alterations, central nervous system immaturity, and alterations in the intestinal microbiota. Several treatment alternatives have been described, including behavioral measures, manipulation techniques, use of medication, and acupuncture, with controversial results and effectiveness. CONCLUSION: Excessive crying in the early months is a prevalent symptom; the pediatrician's attention is necessary to understand and adequately manage the problem and offer support to exhausted parents. The prescription of drugs of questionable action and with potential side effects is not a recommended treatment, except in extreme situations. The effectiveness of dietary treatments and use of probiotics still require confirmation. There is incomplete evidence regarding alternative treatments such as manipulation techniques, acupuncture, and use of the herbal supplements and behavioral interventions. PMID- 26994451 TI - The formation of citizens: the pediatrician's role. AB - OBJECTIVE: This review article aims to define the fundamental role of the pediatrician in the formation of citizens in the 21st century. SOURCE OF DATA: Significant bibliographical contributions produced by neuroscience, ecology, and epigenetics in the early childhood scenario. SYNTHESIS OF DATA: Many diseases that impair the lives of adults result from severe and often uncontrollable disorders that occur in early childhood, an irreplaceable period for the safe construction of the human brain, personality, and intelligence. There is noteworthy scientific evidence that has become unquestionable, according to which abuse and neglect and other forms of violence to which children are exposed during the course of their lives, are the genesis of many physical ailments and other mental diseases, including depressive morbidity and schizophrenia. Conversely, it is also emphasized that healthy practices such as reading and listening to/playing music are able to intensively contribute to the exercise of cognitive capacity inherent to this period of life, as a prerequisite for the acquisition of learning indispensable to the high educational performance during the schooling period. CONCLUSION: In the light of the disclosed scientific evidence, the pediatrician emerges as the most differentiated professional to provide preventive and curative care indispensable to the skilled formation of a healthy citizen. PMID- 26994452 TI - Signs and symptoms of developmental abnormalities of the genitourinary tract. AB - OBJECTIVE: The abnormalities of the genitourinary tract development are the leading cause of chronic kidney disease (CKD) in children. The diagnosis of this disease in Brazil is late and incomplete, which results in increased morbidity and mortality in this age group. Early diagnosis of this condition is the prerogative of generalist pediatricians, and the aim of this study was to review the clinical signs and symptoms associated with developmental abnormalities of the genitourinary tract. DATA SOURCES: Based on the description of a symbolic clinical case, the authors conducted a non-systematic review of medical literature. DATA SYNTHESIS: The results suggest that the following data should be used as a warning for early diagnosis of affected children: (a) combined urinary tract abnormalities (chromosomal abnormalities; sequence of malformations [VACTERLand Prune-Belly]; and musculoskeletal, digestive tract, heart, and nervous system malformations); (b) previous history (congenital anomalies of the kidney and urinary tract [CAKUT] in the family, low birth weight, and oligoamnios); (c) clinical signs (polyuria/nocturia, urinary tract infection, systemic arterial hypertension, failure to thrive, weak urinary stream, difficulty to start urination, distended bladder, non-monosymptomatic enuresis, urinary/urge incontinence, and bowel and bladder dysfunction); and (d) pre- and postnatal ultrasonographic alterations (increased anteroposterior diameter of the renal pelvis, mainly in the third trimester of pregnancy; single kidney; hydronephrosis associated with other abnormalities; and hydronephrosis with parenchymal involvement in the post-neonatal assessment). CONCLUSION: The suggestions shown here can help the pediatrician to establish clinical hypotheses for the early diagnosis of developmental abnormalities of the genitourinary tract without resorting to expensive and invasive procedures. PMID- 26994453 TI - A literature review to evaluate the economic value of ranolazine for the symptomatic treatment of chronic angina pectoris. AB - To conduct a systematic review of the evidence regarding the economic value of ranolazine relative to standard-of-care (SOC) for the treatment of symptomatic chronic stable angina (CSA). Electronic databases were searched using relevant keywords. The identified studies were independently reviewed by two investigators against pre-determined inclusion and exclusion criteria. Their data were extracted using a relevant form and consequently were synthesized. Studies were also evaluated using the Quality of Health Economic Studies scale. The main outcomes considered were the cost and effectiveness for each comparator and the incremental cost per quality-adjusted-life year (QALY) gained. Six studies were included in the review. Five of these assessed the cost-utility of ranolazine added to SOC, compared to SOC alone, using decision trees or Markov models whereas one was a retrospective cost evaluation study. The analysis was conducted from a payer perspective in five studies and from a societal perspective in one study with the time horizon varying between six months and a year. The incremental cost-effectiveness ratio (ICER), ranged from ?4000 to ?15,000 per QALY gained. Ranolazine appears to be dominant or cost-effective, mainly due to its ability to decrease angina-related hospitalizations and also due to a marginal improvement in quality of life. The acquisition cost of ranolazine was the variable with the greatest impact upon the ICER. The existing evidence, although limited, indicates that ranolazine may be a dominant or cost-effective therapy option, for the treatment of patients with symptomatic CSA. Further research is required to evaluate the cost-effectiveness of ranolazine. PMID- 26994454 TI - True left bundle branch block? PMID- 26994455 TI - Does Practice Type Determine the Complexity of Patients Encountered for Orthognathic Surgery? AB - PURPOSE: This study sought to determine whether the type of oral and maxillofacial surgery (OMS) practice dictated the complexity of patients encountered for orthognathic surgery and to determine whether there were meaningful differences in comorbidities between patient groups. MATERIALS AND METHODS: This was a retrospective cohort study of orthognathic surgical patients operated on by surgeons at an academic medical center (AMC; OMS department at the University of Alabama-Birmingham) compared with a private practice (PP) group that also operated at the AMC auxiliary facility. Surgical procedures included in this study were Le Fort osteotomy, bilateral sagittal split osteotomy, genioplasty, and combinations of these procedures. An experienced surgeon scrutinized the medical records of the AMC and PP groups for age, gender, medical history, American Society of Anesthesiologists (ASA) classification, and indications for surgical procedures. These data were statistically compared for differences in patient complexity. RESULTS: The average age of patients in the 2 groups was similar (AMC, 29 yr; PP, 27 yr). Many more females were treated in the PP setting (male-to-female ratio, 1.06:1 in the AMC group and 1:1.6 in the PP group). The AMC group had a larger percentage of patients with medical comorbidities, a larger proportion of patients with ASA class 2 or 3, and a larger proportion of patients who underwent procedures for reasons other than malocclusion or cosmetic purposes, and these proportions were statistically relevant. Average length of surgery and average length of stay were longer in the AMC group. CONCLUSION: This retrospective cohort study suggests that OMS departments in AMCs tend to treat orthognathic surgical patients with increased comorbidities and systemic illnesses and operate on a larger percentage of patients with concomitant dentofacial issues versus more routine dentofacial skeletal and occlusion deformities. PMID- 26994456 TI - Three-Dimensional Computed Tomographic Assessment of Temporomandibular Joint Stability After Orthognathic Surgery. AB - PURPOSE: Ensuring that the condyle is appropriately positioned and that positional changes are minimal is considered crucial for the temporomandibular joint (TMJ) to function without symptoms after orthognathic surgery. The purposes of this study were to evaluate condylar changes after surgery and to examine the association between these changes and TMJ symptoms. PATIENTS AND METHODS: A retrospective cohort study was conducted in patients with mandibular prognathism who underwent orthognathic surgery. Linear and angular changes in the positioning of the condyle were measured by superimposing 3-dimensional computed tomograms taken before surgery and 3 months after surgery. Clinical symptoms of TMJ pain and sound were recorded at 3, 6, 9, and 12 months after surgery. Possible associations between TMJ symptoms and clinical variables, such as postoperative condylar changes, were investigated using multiple logistic regression analysis. RESULTS: Linear condylar displacement after orthognathic surgery occurred predominantly in the anterior, medial, and inferior directions, with minimal changes (<1 mm) observed. Most angular condylar changes were smaller than 4 degrees and occurred in the inward direction in the axial plane and the posterior direction in the sagittal plane. The best predictor of postoperative TMJ signs and symptoms was the preoperative status of TMJ signs and symptoms. Neither linear nor angular condylar displacement showed a relevant influence on postoperative pain and sound. CONCLUSIONS: Within the ranges of linear (<1 mm) and angular (<4 degrees ) condylar displacement noted in this study, displacement was not associated with postoperative TMJ pain and sound. PMID- 26994457 TI - AAOMS Informational Campaign Communicates the OMS Story. PMID- 26994458 TI - A case report on acute severe hyponatraemia following parathyroid surgery for primary hyperparathyroidism-A rare but life threatening complication. AB - INTRODUCTION: Parathyroidectomy is a common operation, which is well tolerated and associated with low morbidity. Patients are usually discharged within 24hours of surgery. Severe postoperative hyponatraemia is a rare complication which can cause significant morbidity including seizure, coma, respiratory arrest and even death. PRESENTATION OF CASE: We present two patients with clinically significant hyponatremia resulting in seizures and collapse within 24hours after parathyroidectomy, an unreported complication following surgery for primary hyperparathyroidism. One patient required support on the High Dependency Unit and both were treated with fluid restriction which resulted in correction of their electrolyte balance. DISCUSSION: We believe this was caused by the relative inability to secrete a water load after surgery and non-psychogenic polydipsia. Preoperatively, neither patient was prescribed any routine medications nor did they have any risk factors for hyponatremia. Both had normal preoperative sodium levels. It is usual practice is to advise patients to increase oral water intake when they are hypercalcaemic. The aim of parathyroidectomy is to treat hypercalcaemia by stopping excess PTH secretion from abnormal parathyroid glands. These patients continued to follow this advice after surgery when they were eucalcaemic after their operation and because they were thirsty. The patients drank several litres of water in 12-24hours after surgery. We believe that this may have contributed to this complication. CONCLUSION: Healthcare professionals need to be aware of this complication and patients should be advised to restrict intake of free water after surgery. PMID- 26994459 TI - Incidence of chemotherapy-induced nausea and vomiting associated with docetaxel and cyclophosphamide in early breast cancer patients and aprepitant efficacy as salvage therapy. Results from the Spanish Breast Cancer Group/2009-02 study. AB - BACKGROUND: Docetaxel-cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients. PATIENTS AND METHODS: This prospective multicentre study enrolled 212 chemotherapy-naive EBC patients receiving T-75 mg/m(2) and C-600 mg/m(2). Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5 hydroxytryptamine (5-HT3) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2. RESULTS: Among the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2-91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8-72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8-38.1, p = 0.0124) and 2 (18.3-42.9, p = 0.0059). CONCLUSIONS: Guideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy. PMID- 26994460 TI - A novel approach for mitigation of membrane fouling: Concomitant use of flocculant and magnetic powder. AB - Membrane fouling alleviation by addition of poly dimethyl diallyl ammonium chloride (PDMDAAC) and magnetic powder (Fe3O4) was investigated. It was found that magnetic powder associated with PDMDAAC had a good performance on mitigation of membrane fouling, improvement in dehydrogenase activity and enhancement of biomass growth. The optimal dose of PDMDAAC was determined by using constant pressure dead-end filtration unit. Maximum permeate flux was attained at 400mg/L of PDMDAAC addition. Continuous experiment was conducted in a submerged membrane bioreactor (MBR) system and biomass parameters such as soluble microbial products (SMP), extracellular polymeric substances (EPS), dehydrogenase activity, zeta potential, and capillary suction time (CST) were analyzed. Best results were obtained with a combination of 120mg/L of magnetic powder and 400mg/L of PDMDAAC. This study results demonstrated that PDMDAAC played a major role in SMPc and EPSc reduction, whereas magnetic powder had better performance in decreasing SMPc and EPSp. PMID- 26994461 TI - Optimizing and real-time control of biofilm formation, growth and renewal in denitrifying biofilter. AB - A pilot-scale denitrifying biofilter (DNBF) with a treatment capacity of 600m(3)/d was used to study real-time control of biofilm formation, removal and renewal. The results showed biofilm formation, growth and removal can be well controlled using on-line monitored turbidity. The status of filter layer condition can be well indicated by Turb break points on turbidity profile. There was a very good linear relationship between biofilm growth degree (Xbiof) and filter clogging degree (Cfilter) with R(2) higher than 0.99. Filter layer clogging coefficient (Yc) lower than 0.27 can be used to determine stable filter layer condition. Since variations of turbidity during backwash well fitted normal distribution with R(2) higher than 0.96, biofilm removal during backwash also can be well optimized by turbidity. Although biofilm structure and nirK-coding denitrifying communities using different carbon sources were much more different, DNBF was still successfully and stably optimized and real-time controlled via on line turbidity. PMID- 26994462 TI - Sequential recycling of enzymatic lipid-extracted hydrolysate in fermentations with a thraustochytrid. AB - This study extends the findings of prior studies proposing and validating nutrient recycling for the heterotrophic microalgae, Thraustochytrium sp. (T18), grown in optimized fed-batch conditions. Sequential nutrient recycling of enzymatically-derived hydrolysate in fermentors succeeded at growing the tested thraustochytrid strain, with little evidence of inhibition or detrimental effects upon culture health. The average maximum biomass obtained in the recycled hydrolysate was 63.68+/-1.46gL(-1) in 90h the first recycle followed by 65.27+/ 1.15gL(-1) in 90h in the subsequent recycle of the same material. These compared to 58.59gL(-1) and 64.92gL(-1) observed in fresh media in the same time. Lipid production was slightly impaired, however, with a maximum total fatty acid content of 62.2+/-0.30% in the recycled hydrolysate compared to 69.4% in fresh control media. PMID- 26994464 TI - Time variability of the north-western Mediterranean Sea pH over 1995-2011. AB - Factors controlling ocean acidification and its temporal variations were studied over the 1995-2011 period at the Dyfamed site at 10 m depth, in the North Mediterranean Sea. The results indicated a mean annual decrease of 0.003 +/- 0.001 pH units on the seawater scale. The seasonal variability was characterized by a pH decrease during springtime and a strong pH increase in late fall. Anthropogenic CO2 (CANT) absorption by the ocean was the key driver of seawater acidification in this region, accounting for about 70% of the observed drop in pH, followed by water temperature (about 30%). The total inorganic carbon (CT) data showed a CT increase of 30.0 +/- 1.0 MUmol kg(-1) per decade. This decadal increase is mainly due to the CANT penetration (43.2 MUmol kg(-1) per decade) in surface waters, which is mitigated for by relatively small opposing changes in CT due to physical and biological processes. PMID- 26994463 TI - The influence of pre-existing health conditions on short-term mortality risks of temperature: Evidence from a prospective Chinese elderly cohort in Hong Kong. AB - BACKGROUND: Both cold and hot temperatures are associated with adverse health outcomes. Less is known about the role of pre-existing medical conditions to confer individual's susceptibility to temperature extremes. METHODS: We studied 66,820 subjects aged >=65 who were enrolled and interviewed in all the 18 Elderly Health Centers of Department of Health, Hong Kong from 1998 to 2001, and followed up for 10-13 years. The distributed lag nonlinear model (DLNM) combined with a nested case-control study design was applied to estimate the nonlinear and delayed effects of cold or hot temperature on all natural mortality among subjects with different pre-existing diseases. RESULTS: The relative risk of all natural mortality associated with a decrease of temperature from 25th percentile (19.5 degrees C) to 1st percentile (11.3 degrees C) over 0-21 lag days for participants who reported to have an active disease at the baseline was 2.21 (95% confidence interval (CI): 1.19, 4.10) for diabetes mellitus (DM), 1.59 (1.12, 2.26) for circulatory system diseases (CSD), and 1.23 (0.53, 2.84) for chronic obstructive pulmonary disease (COPD), whereas 1.04 (0.59, 1.85) for non-disease group (NDG). Compared with NDG, elders with COPD had excess risk of mortality associated with thermal stress attributable to hot temperature, while elders with DM and CSD were vulnerable to both hot and cold temperatures. CONCLUSIONS: Elders with pre-existing health conditions were more vulnerable to excess mortality risk to hot and/or cold temperature. Preventative measures should target on elders with chronic health problems. PMID- 26994465 TI - Complex spatial and temporal variation of subtropical benthic macrofauna under sewage impact. AB - To better understand variation in sewage-impacted benthic macrofauna from subtropical tidal flats over time and space, we applied a five-factor linear model at a hierarchy of spatial (Condition - Contaminated or Non-Contaminated, Tidal Flat and Plot) and temporal scales (Season and Fortnight). The Contaminated site showed high levels of coprostanol and the presence of Paranais cf frici as markers or indicators of organic enrichment. Differences between Seasons were more pronounced for the faunal variation patterns than for the other parameters, with lower species richness and abundance in summer. There were significant interactions between Fortnight and Tidal Flat for most variables, reflecting marked heterogeneity within Tidal Flats. Benthic community has significantly changed over short periods of time. These rapid changes may lead to erroneous interpretations and mask the true sources of variation. Our results clearly demonstrate the need to better understand benthic temporal variability even at small scales. PMID- 26994466 TI - Viable pregnancies beyond 28 weeks gestation in women with a history of unexplained recurrent miscarriage have reduced platelet function. AB - OBJECTIVE: The aim of this study was to characterize platelet function in pregnant patients with a history of unexplained recurrent miscarriage (RM) in the third trimester of a subsequent viable pregnancy, a time at which platelet dysfunction may be associated with an increased obstetric risk. STUDY DESIGN: A prospective study was performed comparing 30 viable pregnancies that had reached at least 28 weeks' gestation amongst patients who had a background history of unexplained RM, with 30 healthy pregnant controls at a similar gestational age. Platelet function was determined by means of platelet aggregation in response to 5 different agonists at multiple concentrations. RESULTS: Amongst the 30 RM patients with ongoing viable pregnancies, we demonstrated significantly reduced platelet aggregation compared to the pregnant controls in the third trimester. For three out of five agonists, we demonstrated statistically significantly decreased platelet aggregation and for all five agonists we demonstrated significantly decreased platelet aggregation in the postnatal period. There were no obvious differences in obstetric outcomes. CONCLUSION: This study shows that women with a history of unexplained RM have reduced platelet function after 28 weeks' gestation in their subsequent pregnancies compared to healthy pregnant controls, but without this difference leading to any obvious increase in adverse obstetric risk. PMID- 26994467 TI - Assessment of motivation to control alcohol use: The motivational thought frequency and state motivation scales for alcohol control. AB - INTRODUCTION: The Elaborated Intrusion Theory of Desire holds that desires for functional and dysfunctional goals share a common form. Both are embodied cognitive events, characterised by affective intensity and frequency. Accordingly, we developed scales to measure motivational cognitions for functional goals (Motivational Thought Frequency, MTF; State Motivation, SM), based on the existing Craving Experience Questionnaire (CEQ). When applied to increasing exercise, MTF and SM showed the same three-factor structure as the CEQ (Intensity, Imagery, Availability). The current study tested the internal structure and concurrent validity of the MTF and SM Scales when applied to control of alcohol consumption (MTF-A; SM-A). METHODS: Participants (N=417) were adult tertiary students, staff or community members who had recently engaged in high-risk drinking or were currently trying to control alcohol consumption. They completed an online survey comprising the MTF-A, SM-A, Alcohol Use Disorders Identification Test (AUDIT), Readiness to Change Questionnaire (RCQ) and demographics. RESULTS: Confirmatory Factor Analysis gave acceptable fit for the MTF-A, but required the loss of one SM-A item, and was improved by intercorrelations of error terms. Higher scores were associated with more severe problems on the AUDIT and with higher Contemplation and Action scores on the RCQ. CONCLUSIONS: The MTF-A and SM-A show potential as measures of motivation to control drinking. Future research will examine their predictive validity and sensitivity to change. The scales' application to both increasing functional and decreasing dysfunctional behaviours is consistent with EI Theory's contention that both goal types operate in similar ways. PMID- 26994468 TI - Nanopuller-open data acquisition platform for AFM force spectroscopy experiments. AB - Atomic Force Microscope (AFM) is a widely used tool in force spectroscopy studies. Presently, this instrument is accessible from numerous vendors, albeit commercial solutions are expensive and almost always hardware and software closed. Approaches for open setups were published, as with modern low cost and readily available piezoelectric actuators, data acquisition interfaces and optoelectronic components building such force spectroscopy AFM is relatively easy. However, suitable software to control such laboratory made instrument was not released. Developing it in the lab requires significant time and effort. Our Nanopuller software described in this paper is intended to eliminate this obstacle. With only minimum adjustments this program can be used to control and acquire data with any suitable National Instruments universal digital/analog interface and piezoelectric actuator analog controller, giving significant freedom and flexibility in designing force spectroscopy experiment. Since the full code, written in a graphical LabVIEW environment is available, our Nanopuller can be easily customized. In this paper we describe the program and test its performance in controlling different setups. Successful and accurate force curve acquisition for standard samples (single molecules of I27O reference titin polyprotein and DNA as well as red blood cells) is shown. PMID- 26994469 TI - Management of liver metastases in colorectal cancer patients: A retrospective case-control study of systemic therapy versus liver resection. AB - OBJECTIVE: To evaluate and compare the overall survival (OS) in case-matched patient groups treated either with systemic therapy or surgery for colorectal liver metastases (CRLM). METHODS: Patients with CRLM, without extra-hepatic disease, treated with chemotherapy with or without targeted therapy in two phase III studies (n = 480) were selected and case-matched to patients who underwent liver resection (n = 632). Matching criteria were sex, age, established prognostic factors for survival (clinical risk score). Available computed tomography (CT)-scans of patients treated with systemic therapies were reviewed by three independent liver surgeons for resectability. Survival was compared between patients with resectable CRLM (based on CT-scan review) who were treated with systemic therapy versus patients who underwent liver resection. RESULTS: A total of 96 patients treated with systemic therapy were included. Pre-treatment CT-scans of the liver were available for review in 56 of the systemically treated patients, and metastases were unanimously considered resectable in 36 patients (64.3%) (complex resectable: n = 25; 69%). These 36 patients were case-matched with 36 patients who underwent liver resection (wedge resection or segmentectomy: n = 26; 72%). Median OS in the patient group treated with systemic therapy was 26.5 months (range 0-81 months), which was significantly lower than that in case matched patients who underwent liver resection (median OS 56 months; range 6-116) (p = 0.027). CONCLUSIONS: In this case-matched control study, surgery provided superior OS rates compared to systemic therapy for CRLM. Resection of CRLM should always be considered, preferably in a dedicated liver centre, since not all patients that qualify for resection are identified as such. PMID- 26994470 TI - Meal-induced platelet activation in diabetes mellitus type 1 or type 2 is related to postprandial insulin rather than glucose levels. AB - AIM: Postprandial platelet activation was related to postprandial insulin rather than glucose levels in a previous meal insulin study in type 2 diabetes mellitus (T2DM). We therefore compared postprandial platelet activation in type 1 (T1DM) patients without insulin secretion and T2DM patients with high postprandial insulin levels. MATERIAL AND METHODS: Patients with T1DM (n=11) and T2DM (n=12) were studied before and 90min after a standardized meal without premeal insulin. Five T1DM patients volunteered for a restudy with their regular premeal insulin. Platelet activation was assessed by flow cytometry, with and without the thromboxane analogue U46619 or ADP, and by whole blood aggregometry (Multiplate(r)). Effects of insulin (100MUU/mL) in vitro were also studied. RESULTS: Before the meal, glucose, insulin and platelet activation markers other than platelet-leukocyte aggregates (PLAs) were similar in T1DM and T2DM; PLAs were higher in T1DM. Postprandial glucose levels increased more markedly in T1DM (to 22.1+/-1.4 vs. 11.2+/-0.6mmol/L) while insulin levels increased only in T2DM (from 24.4+/-4.4 to 68.8+/-12.3MUU/mL). Platelet P-selectin expression, fibrinogen binding and PLA formation stimulated by U46619 were markedly enhanced (approximately doubled) and whole blood aggregation stimulated by U46619 was increased (p<0.05 for all) after the meal in T2DM patients but not in T1DM patients. The pilot study with premeal insulin in T1DM patients showed postprandial platelet activation when postprandial insulin levels increased. In vitro insulin mildly activated platelets in both groups. CONCLUSION: Postprandial platelet activation via the thromboxane pathway is related to postprandial hyperinsulinemia and not to postprandial hyperglycaemia in patients with diabetes. PMID- 26994471 TI - Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction. AB - INTRODUCTION: Fondaparinux (FDX) was demonstrated to be cardioprotective in a rat model of myocardial ischemia reperfusion. In this model, FDX reduced infarct size after 2h of reperfusion, involving the activation of the survivor activating factor enhancement (SAFE) pathway as early as 30min post-reperfusion. Our aim was to study if this cardioprotection could be explained by anti-inflammatory mechanisms and a protective effect on vessels. METHODS: Wistar male rats were subjected to 40minutes (min) of myocardial ischemia, followed by 30min or 2h of reperfusion. Rats were randomized into four groups: control 30min (n=7), FDX 30min (n=7), control 2h (n=7), and FDX 2h (n=7). The FDX groups received 10mg/kg injection of FDX 10min prior to initiating reperfusion. We studied: 1) mRNA expression of endothelial markers, such as thrombomodulin (TM), endothelial protein C receptor (EPCR), and tissue factor (TF) and 2) proteic expression of ICAM-1, NF-kappaB, IkappaB, and JNK. Leukocyte infiltration was assessed by histochemistry. We also evaluated TM and EPCR mRNA expression in a model of isolated rat mesenteric arteries incubated with FDX. RESULTS: FDX upregulated the expression of TM and EPCR mRNA in the models of myocardial infarction and isolated mesenteric arteries. No difference was observed between the treated and control groups regarding the expression of pro-inflammatory signaling proteins, adhesion molecules, and leukocyte infiltration after 2h of reperfusion. CONCLUSION: The cardioprotective effect of FDX at early-stage reperfusion could be related to vascular protection, yet not to an anti-inflammatory effect. PMID- 26994473 TI - Exploring Ethnic Differences in Taste Perception. AB - It is well known that nutritional intake can vary substantially as a function of demographic variables such as ethnicity and/or sex. Although a variety of factors are known to underlie the relationship between these demographic variables and nutritional intake, it is interesting to speculate that variation in food intake associated with ethnicity or sex may result, in part, from differences in the perceived taste of foods in these different populations. Thus, we initiated a study to evaluate taste responsiveness in different ethnic groups. Moreover, because of the known differences in taste responsiveness between males and females, analyses were stratified by sex. The ethnic groups tested differed significantly from one another in reported perceived taste intensity. Our results showed that Hispanics and African Americans rated taste sensations higher than non-Hispanic Whites and that these differences were more pronounced in males. Understanding the nature of these differences in taste perception is important, because taste perception may contribute to dietary health risk. When attempting to modify diet, individuals of different ethnicities may require personalized interventions that take into account the different sensory experience that these individuals may have when consuming foods. PMID- 26994474 TI - Photorespiratory glycolate oxidase is essential for the survival of the red alga Cyanidioschyzon merolae under ambient CO2 conditions. AB - Photorespiration is essential for all organisms performing oxygenic photosynthesis. The evolution of photorespiratory metabolism began among cyanobacteria and led to a highly compartmented pathway in plants. A molecular understanding of photorespiration in eukaryotic algae, such as glaucophytes, rhodophytes, and chlorophytes, is essential to unravel the evolution of this pathway. However, mechanistic detail of the photorespiratory pathway in red algae is scarce. The unicellular red alga Cyanidioschyzon merolae represents a model for the red lineage. Its genome is fully sequenced, and tools for targeted gene engineering are available. To study the function and importance of photorespiration in red algae, we chose glycolate oxidase (GOX) as the target. GOX catalyses the conversion of glycolate into glyoxylate, while hydrogen peroxide is generated as a side-product. The function of the candidate GOX from C. merolae was verified by the fact that recombinant GOX preferred glycolate over L-lactate as a substrate. Yellow fluorescent protein-GOX fusion proteins showed that GOX is targeted to peroxisomes in C. merolae The GOX knockout mutant lines showed a high-carbon-requiring phenotype with decreased growth and reduced photosynthetic activity compared to the wild type under ambient air conditions. Metabolite analyses revealed glycolate and glycine accumulation in the mutant cells after a shift from high CO2 conditions to ambient air. In summary, or results demonstrate that photorespiratory metabolism is essential for red algae. The use of a peroxisomal GOX points to a high photorespiratory flux as an ancestral feature of all photosynthetic eukaryotes. PMID- 26994475 TI - 2,4-D resistance in wild radish: reduced herbicide translocation via inhibition of cellular transport. AB - Resistance to auxinic herbicides is increasing in a range of dicotyledonous weed species, but in most cases the biochemical mechanism of resistance is unknown. Using (14)C-labelled herbicide, the mechanism of resistance to 2,4 dichlorophenoxyacetic acid (2,4-D) in two wild radish (Raphanus raphanistrum L.) populations was identified as an inability to translocate 2,4-D out of the treated leaf. Although 2,4-D was metabolized in wild radish, and in a different manner to the well-characterized crop species wheat and bean, there was no difference in metabolism between the susceptible and resistant populations. Reduced translocation of 2,4-D in the latter was also not due to sequestration of the herbicide, or to reduced uptake by the leaf epidermis or mesophyll cells. Application of auxin efflux or ABCB transporter inhibitors to 2,4-D-susceptible plants caused a mimicking of the reduced-translocation resistance phenotype, suggesting that 2,4-D resistance in the populations under investigation could be due to an alteration in the activity of a plasma membrane ABCB-type auxin transporter responsible for facilitating long-distance transport of 2,4-D. PMID- 26994472 TI - Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition. AB - OBJECTIVE: The aim of this study was to determine gene expression and splicing changes associated with parturition and regions (visceral vs. subcutaneous) of the adipose tissue of pregnant women. STUDY DESIGN: The transcriptome of visceral and abdominal subcutaneous adipose tissue from pregnant women at term with (n=15) and without (n=25) spontaneous labor was profiled with the Affymetrix GeneChip Human Exon 1.0 ST array. Overall gene expression changes and the differential exon usage rate were compared between patient groups (unpaired analyses) and adipose tissue regions (paired analyses). Selected genes were tested by quantitative reverse transcription-polymerase chain reaction. RESULTS: Four hundred and eighty-two genes were differentially expressed between visceral and subcutaneous fat of pregnant women with spontaneous labor at term (q-value <0.1; fold change >1.5). Biological processes enriched in this comparison included tissue and vasculature development as well as inflammatory and metabolic pathways. Differential splicing was found for 42 genes [q-value <0.1; differences in Finding Isoforms using Robust Multichip Analysis scores >2] between adipose tissue regions of women not in labor. Differential exon usage associated with parturition was found for three genes (LIMS1, HSPA5, and GSTK1) in subcutaneous tissues. CONCLUSION: We show for the first time evidence of implication of mRNA splicing and processing machinery in the subcutaneous adipose tissue of women in labor compared to those without labor. PMID- 26994476 TI - A single cytosine deletion in the OsPLS1 gene encoding vacuolar-type H+-ATPase subunit A1 leads to premature leaf senescence and seed dormancy in rice. AB - Leaf senescence is a programmed developmental process orchestrated by many factors, but its molecular regulation is not yet fully understood. In this study, a novel Oryza sativa premature leaf senescence mutant (ospls1) was examined. Despite normal development in early seedlings, the ospls1 mutant leaves displayed lesion-mimics and early senescence, and a high transpiration rate after tillering. The mutant also showed seed dormancy attributable to physical (defect of micropyle structure) and physiological (abscisic acid sensitivity) factors. Using a map-based cloning approach, we determined that a cytosine deletion in the OsPLS1 gene encoding vacuolar H(+)-ATPase subunit A1 (VHA-A1) underlies the phenotypic abnormalities in the ospls1 mutant. The OsPSL1/VHA-A1 transcript levels progressively declined with the age-dependent leaf senescence in both the ospls1 mutant and its wild type. The significant decrease in both OsPSL1/VHA-A1 gene expression and VHA enzyme activity in the ospls1 mutant strongly suggests a negative regulatory role for the normal OsPLS1/VHA-A1 gene in the onset of rice leaf senescence. The ospls1 mutant featured higher salicylic acid (SA) levels and reactive oxygen species (ROS) accumulation, and activation of signal transduction by up-regulation of WRKY genes in leaves. Consistent with this, the ospls1 mutant exhibited hypersensitivity to exogenous SA and/or H2O2 Collectively, these results indicated that the OsPSL1/VAH-A1 mutation played a causal role in premature leaf senescence through a combination of ROS and SA signals. To conclude, OsPLS1 is implicated in leaf senescence and seed dormancy in rice. PMID- 26994477 TI - Chloroplasts at work during plant innate immunity. AB - The major role played by chloroplasts during light harvesting, energy production, redox homeostasis, and retrograde signalling processes has been extensively characterized. Beyond the obvious link between chloroplast functions in primary metabolism and as providers of photosynthesis-derived carbon sources and energy, a growing body of evidence supports a central role for chloroplasts as integrators of environmental signals and, more particularly, as key defence organelles. Here, we review the importance of these organelles as primary sites for the biosynthesis and transmission of pro-defence signals during plant immune responses. In addition, we highlight interorganellar communication as a crucial process for amplification of the immune response. Finally, molecular strategies used by microbes to manipulate, directly or indirectly, the production/function of defence-related signalling molecules and subvert chloroplast-based defences are also discussed. PMID- 26994478 TI - Photorespiratory glycolate-glyoxylate metabolism. AB - Photorespiration is one of the major carbon metabolism pathways in oxygen producing photosynthetic organisms. This pathway recycles 2-phosphoglycolate (2 PG), a toxic metabolite, to 3-phosphoglycerate when ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) uses oxygen instead of carbon dioxide. The photorespiratory cycle is in competition with photosynthetic CO2 fixation and it is accompanied by carbon, nitrogen and energy losses. Thus, photorespiration has become a target to improve crop yields. Moreover, during the photorespiratory cycle intermediate metabolites that are toxic to Calvin-Benson cycle and RuBisCO activities, such as 2-PG, glycolate and glyoxylate, are produced. Thus, the presence of an efficient 2-PG/glycolate/glyoxylate 'detoxification' pathway is required to ensure normal development of photosynthetic organisms. Here we review our current knowledge concerning the enzymes that carry out the glycolate glyoxylate metabolic steps of photorespiration from glycolate production in the chloroplasts to the synthesis of glycine in the peroxisomes. We describe the properties of the proteins involved in glycolate-glyoxylate metabolism in Archaeplastida and the phenotypes observed when knocking down/out these specific photorespiratory players. Advances in our understanding of the regulation of glycolate-glyoxylate metabolism are highlighted. PMID- 26994479 TI - Anatomic placement of the femoral tunnel by a modified transtibial technique using a large-offset femoral tunnel guide: A cadaveric study. AB - BACKGROUND: The purpose of this study was to assess whether the use of a 10 mm offset femoral tunnel guide with lateral rotation allows more anatomic placement of femoral tunnel compared to the conventional seven millimeters-offset guide in transtibial anterior cruciate ligament (ACL) reconstruction. METHODS: Sixteen knees from eight cadavers were employed. Four guide pins were inserted using a seven millimeters- or 10mm-offset transtibial femoral tunnel guide with or without lateral rotation technique in each knee. The pin positions were assessed by the quadrant method. Femoral tunnels were then reamed along the guide pins inserted through the laterally rotated guides: seven millimeters-offset for right knees and 10 mm- offset for left knees. The percentages of the coverage of native ACL femoral footprints were analyzed. RESULTS: Lateral rotation of the seven millimeters- & 10mm-offset guides placed the pins more posteriorly (lower) by 15.7% and 24.5%, respectively (p<0.001). Laterally rotated 10 mm-offset guides placed the guide pins more distally by 6.2% and more posteriorly by 6.6% than laterally rotated seven millimeters-offset guides. Laterally rotated seven millimeters- & 10 mm-offset guides resulted in average coverage of 52.3% and 61.8% of the native ACL femoral footprints, respectively (p<0.001). The lengths of the tunnels were acceptable. CONCLUSION: Compared to the conventional seven millimeters-offset guide, the use of a 10mm-offset femoral tunnel guide with lateral rotation allows more anatomic placement of femoral tunnel in transtibial ACL reconstruction. CLINICAL RELEVANCE: Anatomic single bundle ACL reconstruction by transtibial technique seems feasible by using the technique described in this study. PMID- 26994480 TI - Femoral insertion site in medial patellofemoral ligament reconstruction. AB - BACKGROUND: The optimal femoral insertion point in MPFL (medial patellofemoral ligament)-reconstruction still remains ambiguous. Three-dimensional knee simulations based on computerized tomography (CT) images acquired under physiological loading conditions give further insights to predict the optimal femoral insertion site of the MPFL. The hypothesis of the present study is that the optimal insertion point is not as reliable as thought and is dependent on subject-specific anatomical factors. METHODS: High-resolution 3D images of the knee were acquired in ten weight-bearing knees of healthy subjects in five flexion angles (0 to 120 degrees ). The distance between different femoral insertion points and two defined patellar points was computed in each position to quantify length of respective bundles and isometry of the femoral insertion site. RESULTS: The median length of both bundles was maximal in full extension (proximal bundle: 62.2mm and distal bundle: 59.9mm). The shortest ligament length was obtained in the flexion position 90 degrees for bundle I (57.3mm) and 30 degrees for bundle II (85.3mm). The calculated most isometric femoral attachment point showed a non-uniform distribution pattern related to anatomic landmarks. The radiographic landmark showed the worst isometric score value compared to virtually defined spots by surgeons and the computed most isometric point. CONCLUSIONS: This study provides results on the MPFL path length under physiological loading conditions using high-resolution bone geometry. The most important finding of this study was that the computed, best isometric femoral insertion point showed a variable anatomical distribution. This suggests that the optimal position for femoral MPFL-graft fixation is patient specific. PMID- 26994481 TI - Medial unicompartmental knee arthroplasty improves congruence and restores joint space width of the lateral compartment. AB - BACKGROUND: Osteoarthritic progression of the lateral compartment remains a leading indication for medial unicompartmental knee arthroplasty (UKA) revision. Therefore, the purpose of this study was to evaluate the alterations of the lateral compartment congruence and joint space width (JSW) following medial UKA. METHODS: Retrospectively, lateral compartment congruence and JSW were evaluated in 174 knees (74 females, 85 males, mean age 65.5years; SD+/-10.1) preoperatively and six weeks postoperatively, and compared to 41 healthy knees (26 men, 15 women, mean age 33.7years; SD+/-6.4). Congruence (CI) was calculated using validated software that evaluates the geometric relationship between surfaces and calculates a congruence index (CI). JSW was measured on three sides (inner, middle, outer) by subdividing the lateral compartment into four quarters. RESULTS: The CI of the control group was 0.98 (SD+/-0.01). The preoperative CI was 0.88 (SD+/-0.01), which improved significantly to 0.93 (SD+/-0.03) postoperatively (p<0.001). In 82% of knees, CI improved after surgery, while in 18% it decreased. The preoperative significant JSW differences of the inner (p<0.001) and outer JSW (p<0.001) were absent postoperatively. CONCLUSION: Our data suggests that a well-conducted medial UKA not only resurfaces the medial compartment but also improves congruence and restores the JSW of the lateral compartment. PMID- 26994482 TI - Higher macrophage superoxide anion production in coronary artery disease (CAD) patients with Type D personality. AB - BACKGROUND: Type D personality (Type D) is an independent psychosocial risk factor for poor cardiac prognosis and increased mortality in patients with cardiovascular disease (CVD), but the involved mechanisms are poorly understood. Macrophages play a pivotal role in atherosclerosis, the process underlying coronary artery disease (CAD). We investigated macrophage superoxide anion production in production in CAD patients with and without Type D. METHODS AND RESULTS: We studied 20 male CAD patients with Type D (M:66.7+/-9.9years) and 20 age-matched male CAD patients without Type D (M:67.7+/-8.5years). Type D was measured using the DS14 questionnaire with the two subscales 'negative affectivity' and 'social inhibition'. We assessed macrophage superoxide anion production using the WST-1 assay. All analyses were controlled for potential confounders. CAD patients with Type D showed higher superoxide anion production compared to CAD patients without Type D (F(1,38)=15.57, p<0.001). Complementary analyses using the Type D subscales 'negative affectivity' and 'social inhibition', and their interaction as continuous measures, showed that both Type D subscales (negative affectivity: (beta=0.48, p=0.002, R(2)=0.227); social inhibition: (beta=0.46, p=0.003, R(2)=0.208)) and their interaction (beta=0.36, p=0.022, R(2)=0.130) were associated with higher WST-1 reduction scores. Results remained significant when controlling for classical CVD risk factors (i.e. body mass index, mean arterial blood pressure), atherosclerosis severity (i.e. intima media thickness, presence of carotid plaques), and psychological factors (depressive symptom severity, chronic stress). CONCLUSIONS: Our results indicate higher macrophage superoxide anion production in CAD patients with Type D compared to those without Type D. This may suggest a mechanism contributing to increased morbidity and mortality in CAD patients with Type D. PMID- 26994483 TI - Testosterone reduces functional connectivity during the 'Reading the Mind in the Eyes' Test. AB - Women on average outperform men in cognitive-empathic abilities, such as the capacity to infer motives from the bodily cues of others, which is vital for effective social interaction. The steroid hormone testosterone is thought to play a role in this sexual dimorphism. Strikingly, a previous study shows that a single administration of testosterone in women impairs performance on the 'Reading the Mind in Eyes' Test (RMET), a task in which emotions have to be inferred from the eye-region of a face. This effect was mediated by the 2D:4D ratio, the ratio between the length of the index and ring finger, a proxy for fetal testosterone. Research in typical individuals, in individuals with autism spectrum conditions (ASC), and in individuals with brain lesions has established that performance on the RMET depends on the left inferior frontal gyrus (IFG). Using functional magnetic resonance imaging (fMRI), we found that a single administration of testosterone in 16 young women significantly altered connectivity of the left IFG with the anterior cingulate cortex (ACC) and the supplementary motor area (SMA) during RMET performance, independent of 2D:4D ratio. This IFG-ACC-SMA network underlies the integration and selection of sensory information, and for action preparation during cognitive empathic behavior. Our findings thus reveal a neural mechanism by which testosterone can impair emotion-recognition ability, and may link to the symptomatology of ASC, in which the same neural network is implicated. PMID- 26994484 TI - Comment: Hospital to specific skilled nursing facility linkages-More may be better. PMID- 26994485 TI - The Kampo medicine "Daikenchuto (TU-100)" prevents bacterial translocation and hepatic fibrosis in a rat model of biliary atresia. AB - BACKGROUND: Biliary atresia is the most common cause of end-stage liver disease in children. It is known that bile duct ligation contributes to liver fibrosis via bacterial translocation (BT) and toll-like receptor 4 (TLR4) signaling of hepatic stellate cells (HSCs). We have reported previously that the traditional Japanese medicine, "Dai-kenchu-to (TU-100)," a form of "Kampo medicine" prevents BT in rats exposed to the stress of fasting. The aim of this study was to clarify the effect of TU-100 on a rat model of biliary atresia using bile duct ligation. METHODS: Bile duct ligation and subsequent daily oral administration of TU-100 was performed in 6-week-old rats. The rats were killed at 3, 7, or 14 days after bile duct ligation to evaluate the liver injury, occurrence of BT, and hepatic fibrosis. As an in vitro experiment, we isolated fresh HSCs from the rats undergoing bile duct ligation. After cell attachment, TU-100 and its 3 component herbs (eg, processed ginger, ginseng radix, and Japanese pepper) were added, and the expressions of Alpha actin2 (acta2), Alpha-1 type I collagen (colIa1), and tissue inhibitor of metalloproteinase 1 (timp1) were analyzed. RESULTS: In vivo experiments demonstrated that oral administration of TU-100 decreased liver injury and atrophy of intestinal mucosa BT, hepatic fibrosis, and hepatic expression of alpha smooth muscle actin (alphaSMA) and TLR4, compared with rats that underwent bile duct ligation only. In vitro experiments showed that administration of TU-100 or the component herbs inhibited the expressions of acta2, colIa1, and timp1 in the HSCs. CONCLUSION: TU-100 prevented BT, activation of HSCs, and subsequent hepatic fibrosis. TU-100 may prevent progression of hepatic fibrosis in children with biliary atresia and improve prognosis. PMID- 26994486 TI - Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer. AB - BACKGROUND: The objective of this study was to determine the rate and pattern of nodal recurrence in patients who underwent a therapeutic, lateral neck dissection (LND) for papillary thyroid cancer (PTC) with clinically evident cervical metastases and to determine if there was any correlation between the extent of initial dissection and the rate and pattern of neck recurrence. METHODS: A total of 3,664 patients with PTC treated between 1986 and 2010 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. Tumor factors, patient demographics, extent of initial LND, and adjuvant therapy were recorded. Patterns of recurrent lateral neck metastases by level involvement were recorded and outcomes calculated using the Kaplan-Meier method. RESULTS: A total of 484 patients had an LND for cervical metastases; 364 (75%) had a comprehensive LND (CLND) and 120 (25%) had a selective neck dissection (SND). The median duration of follow-up was 63.5 months. As expected, patients with CLND had a greater number of nodes removed as well as a greater number of positive nodes (P < .001). There was no difference in overall lateral neck recurrence-free status (CLND 94.4% vs SND 89.4%, P = .158), but in the dissected neck, the ipsilateral lateral neck recurrence-free status was superior in the CLND patients (97.7% vs 89.4%, P < .001). CONCLUSION: Patients with clinically evident neck metastases from PTC managed by CLND have lesser rates of recurrence in the dissected neck compared with patients managed by SND. SND should only be done in highly selected cases with small volume disease. PMID- 26994488 TI - Differential genotoxic and epigenotoxic effects of graphene family nanomaterials (GFNs) in human bronchial epithelial cells. AB - The widespread applications of graphene family nanomaterials (GFNs) raised the considerable concern over human health and environment. The cyto-genotoxic potentiality of GFNs has attracted much more attention, albeit the potential effects on the cellular epigenome remain largely unknown. The effects of GFNs on cellular genome were evaluated with single and double stranded DNA damage and DNA repair gene expressions while the effects on epigenome was accomplished by addressing the global DNA methylation and expression of DNA methylation machineries at non-cytotoxic to moderately cytotoxic doses in in vitro system. We used five different representatives of GFNs-pristine (GNP-Prist), carboxylated (GNP-COOH) and aminated (GNP-NH2) graphene nanoplatelets as well as single layer (SLGO) and few layer (FLGO) graphene oxide. The order of single stranded DNA damage was observed as GNP-Prist >= GNP-COOH>GNP-NH2>=FLGO>SLGO at 10mg/L and marked dose dependency was found in SLGO. The GFNs possibly caused genotoxicity by affecting nucleotide excision repair and non-homologus end joining repair systems. Besides, dose dependent increase in global DNA methylation (hypermethylation) were observed in SLGO/FLGO exposure and conversely, GNPs treatment caused hypomethylation following the order as GNP-COOH>GNP-NH2 >= GNP Prist. The decrements of DNA methyltransferase (DNMT3B gene) and methyl-CpG binding domain protein (MBD1) genes were probably the cause of global hypomethylation induced by GNPs. Conversely, the de novo methylation through the up-regulation of DNMT3B and MBD1 genes gave rise to the global DNA hypermethylation in SLGO/FLGO treated cells. In general, the GFNs induced genotoxicity and alterations of global DNA methylation exhibited compounds type specificity with differential physico-chemical properties. Taken together, our study suggests that the GFNs could cause more subtle changes in gene expression programming by modulating DNA methylation status and this information would be helpful for their prospective use in biomedical field. PMID- 26994487 TI - Male breast cancer, clinical presentation, diagnosis and treatment: Twenty years of experience in our Breast Unit. AB - BACKGROUND: The male breast cancer (MBC) is a rare and represents less than 1% of all malignancies in men and only 1% of all breast cancers incident. We illustrate the experience of our team about the clinico-pathological characteristics, treatment and prognostic factors of patients treated over a period of twenty years . RESULTS: Forty-seven patients were collected 1995-2014 at the Breast Unit of the Hospital of Terni, Italy. The average age was 67 years and the median time to diagnosis from the onset of symptoms was 16 months. The main clinical complaint was sub areolar swelling in 36, 76% of cases. Most patients have come to our attention with advanced disease. The histology of about ninety percent of the tumors were invasive ductal carcinoma. Management consisted mainly of radical mastectomy; followed by adjuvant radiotherapy and hormonal therapy with or without chemotherapy. The median follow-up was 38 months. The evolution has been characterized by local recurrences; in eight cases (17% of all patients). Metastasis occurred in 15 cases (32% of all patients). The site of bone metastases was in eight cases; lung in four cases; liver in three cases; liver and skin in one case and pleura and skin in one case. CONCLUSION: The male breast cancer has many similarities to breast cancer in women, but there are distinct functions that need to be appreciated. Future research for a better understanding of the disease should provide a better account of genetic and epigenetic characteristics of these forms; but, above all, epidemiological and biological cohorts numerically more consistent. PMID- 26994489 TI - In vitro evaluation of the cyto-genotoxic potential of Ruthenium(II) SCAR complexes: a promising class of antituberculosis agents. AB - Tuberculosis is a top infectious disease killer worldwide, caused by the bacteria Mycobacterium tuberculosis. Increasing incidences of multiple drug-resistance (MDR) strains are emerging as one of the major public health threats. However, the drugs in use are still incapable of controlling the appalling upsurge of MDR. In recent years a marked number of research groups have devoted their attention toward the development of specific and cost-effective antimicrobial agents against targeted MDR-Tuberculosis. In previous studies, ruthenium(II) complexes (SCAR) have shown a promising activity against MDR-Tuberculosis although few studies have indeed considered ruthenium toxicity. Therefore, within the preclinical requirements, we have sought to determine the cyto-genotoxicity of three SCAR complexes in this present study. The treatment with the SCARs induced a concentration-dependent decrease in cell viability in CHO-K1 and HepG2 cells. Based on the clonogenic survival, SCAR 5 was found to be more cytotoxic while SCAR 6 exhibited selectivity action on tumor cells. Although SCAR 4 and 5 did not indicate any mutagenic activity as evidenced by the Ames and Cytokinesis block micronucleus cytome assays, the complex SCAR 6 was found to engender a frameshift mutation detected by Salmonella typhimurium in the presence of S9. Similarly, we observed a chromosomal damage in HepG2 cells with significant increases of micronuclei and nucleoplasmic bridges. These data indicate that SCAR 4 and 5 complexes did not show genotoxicity in our models while SCAR 6 was considered mutagenic. This study presented a comprehensive genotoxic evaluation of SCAR complexes were shown to be genotoxic in vitro. All in all, further studies are required to fully elucidate how the properties can affect human health. PMID- 26994490 TI - Vitamin D3 deficiency increases DNA damage and the oxidative burst of neutrophils in a hypertensive rat model. AB - Deficiency of vitamin D3, a lipophilic micronutrient, plays a role in the development of some chronic diseases. Vitamin D3 deficiency affects 25-50% of the human population and has been associated with increased risk for development of hypertension. DNA damage induced by reactive oxygen species (ROS) occurs more often in hypertensive than in normotensive individuals, and vitamin D3 status can influence this relationship. The aim of this study was to evaluate whether a diet supplemented with (10,000 IU/kg) or deficient in (0 IU/kg) vitamin D3, compared to a vitamin D3 control diet (1000 IU/kg), would modulate DNA damage and ROS production in spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats after 12 weeks of treatment. ROS production was assessed by measuring the oxidative burst of neutrophils. DNA damage was evaluated using the comet assay in peripheral blood and the micronucleus test in bone marrow and peripheral blood. Vitamin D3 supplementation did not induce DNA damage and did not change neutrophil ROS production in SHR and WKY rats. Vitamin D3 deficiency induced neutrophil ROS production and a high frequency of micronucleus formation in the bone marrow and peripheral blood of SHR rats only, and induced DNA damage (comet) in peripheral blood of both SHR and WKY rats. In conclusion, vitamin D3 deficiency showed a more pronounced effect on hypertensive animals. Population studies are needed to test whether this relationship also exists in humans. PMID- 26994491 TI - DNA damage and repair kinetics of the Alternaria mycotoxins alternariol, altertoxin II and stemphyltoxin III in cultured cells. AB - The Alternaria mycotoxins alternariol (AOH) and altertoxin II (ATX II) have previously been shown to elicit mutagenic and genotoxic effects in bacterial and mammalian cells, although with vastly different activities. For example, ATX II was about 50 times more mutagenic than AOH. We now report that stemphyltoxin III (STTX III) is also highly mutagenic. The more pronounced effects of the perylene quinones ATX II and STTX III at lower concentrations compared to the dibenzo alpha-pyrone AOH indicate a marked dependence of the genotoxic potential on the chemical structure and furthermore suggest that the underlying modes of action may be different. We have now further investigated the type of DNA damage induced by AOH, ATX II and STTX III, as well as the repair kinetics and their dependence on the status of nucleotide excision repair (NER). DNA double strand breaks induced by AOH due to poisoning of topoisomerase IIalpha were completely repaired in less than 2h. Under cell-free conditions, inhibition of topoisomerase IIalpha could also be measured for ATX II and STTX III at low concentrations, but the perylene quinones were catalytic inhibitors rather than topoisomerase poisons and did not induce DSBs. DNA strand breaks induced by ATX II and STTX III were more persistent and not completely repaired within 24h. A dependence of the repair rate on the NER status could only be demonstrated for STTX III, resulting in an accumulation of DNA damage in NER-deficient cells. Together with the finding that the DNA glycosylase formamidopyrimidine-DNA glycosylase (Fpg), but not T4 endonuclease V, is able to generate additional DNA strand breaks measurable by the alkaline unwinding assay, we conclude that the genotoxicity of the perylene quinones with an epoxide group is probably caused by the formation of DNA adducts which may be converted to Fpg sensitive sites. PMID- 26994492 TI - Genotoxicity and cytotoxicity of chromium, copper, manganese and lead, and their mixture in WIL2-NS human B lymphoblastoid cells is enhanced by folate depletion. AB - Heavy metal exposure or dietary deficiency is associated with increased genetic damage, cancer and age-related diseases. Folate (vitamin B9) required for DNA repair and synthesis may increase cellular susceptibility to metal induced genotoxicity. This study investigated the interactive effects of folic acid deficiency and sufficiency on genome instability and cytotoxicity induced by chromium (VI), copper (II), manganese (II), lead (IV), and their mixture (CCMP) in WIL2-NS human B lymphoblastoid cells. WIL2-NS cells were cultured in folic acid deficient (20 nM) and replete (2000 nM) RPMI 1640 medium treated with different concentrations (0.00-1000 MUM) of the metals and CCMP for 48 h. Chromosomal damage and cytotoxicity were measured using the Cytokinesis-block Micronucleus Cytome assay. CCMP, Cr, Pb, Cu and Mn induced concentration dependent, increases in cells with chromosome damage (micronuclei, nucleoplasmic bridges, nuclear buds) and necrotic cells and decreased nuclear division index. The metals exhibited different cytotoxic and genotoxic potentials (CCMP>Cr>Pb>Cu>Mn) in both folate deficient and sufficient cells, with the cytogenotoxic effects being greater in folate deficient cells. Significant interaction between the metals and folic acid suggests that folic acid deficiency exacerbated cell proliferation inhibition and genome instability induced by metals. Folate deficiency, increasing metal concentration, and their interactions explained 3-11%, 74-92% and 4-12% of the variance of DNA damage biomarkers. In conclusion, exposure to the tested metals (0.01-1000 MUM) increased chromosomal DNA damage in WIL2-NS cells and this was exacerbated by folate deficiency. PMID- 26994493 TI - Risk assessment of a cold argon plasma jet in respect to its mutagenicity. AB - Cold atmospheric pressure plasmas represent a favorable option for the treatment of heat sensitive materials and human or animal tissue. Beneficial effects have been documented in a variety of medical conditions, e.g., in the treatment of chronic wounds. It is assumed that the main mechanism of the plasma's efficacy is mediated by a stimulating dissipation of energy via radiation and/or chemical energy. Although no evidence on undesired side effects of a plasma treatment has yet been presented, skepticism toward the safety of the exposure to plasma is present. However, only little data regarding the mutagenic potential of this new treatment option is available. Accordingly, we investigated the mutagenic potential of an argon plasma jet (kinpen) using different testing systems in accordance with ISO norms and multiple cell lines: a HPRT1 mutation assay, a micronucleus formation assay, and a colony formation assay. Moderate plasma treatment up to 180 s did not increase genotoxicity in any assay or cell type investigated. We conclude that treatment with the argon plasma jet kinpen did not display a mutagenic potential under the test conditions applied and may from this perspective be regarded as safe for the use in biomedical applications. PMID- 26994494 TI - New insights into the role of the Brdt protein in the regulation of development and spermatogenesis in the mouse. AB - The bromodomain testis-specific (BRDT) protein belongs to the bromodomain extra terminal (BET) family of proteins. It serves as a transcriptional regulator of gene expression during spermatogenesis, and is an essential factor for the normal spermatogenesis process. In this study, we characterized mice of several age groups who lacked the Brdt gene. The testes of Brdt mutant mice aged 8 weeks exhibited complete spermatocyte maturation arrest with a significantly increased number of apoptotic cells. The weights of the testes and accessory glands as well as the testosterone levels of the mutant mice were significantly lower compared to the normal mice. The mutant mice had delayed puberty, with normal levels of testosterone and accessory gland weights at the age of 14 and 28 weeks. The testes of the mutant mice at older ages also exhibited round spermatids. The presence of the BRDT protein was identified in the mice pituitary gland. Microarray analysis of mice pituitaries showed that 28 genes were down-regulated while 26 genes were up-regulated in the absence of the Brdt gene. Our results suggest that in addition to its critical role in the spermatogenesis process, the BRDT protein is also responsible for scheduling male puberty by regulation of the pituitary-gonad axis. PMID- 26994495 TI - Prehospital Trauma Life Support for Companion Animals and 'Operational Canines'. PMID- 26994496 TI - Best practice recommendations for prehospital veterinary care of dogs and cats. AB - OBJECTIVE: To examine available evidence on prehospital care in human and veterinary trauma and emergency medicine and develop best practice guidelines for use by both paramedical and nonparamedical personnel in the approach to the prehospital care of dogs and cats. DESIGN: Systematic evaluation of the literature gathered via medical databases searches of Medline, CAB abstracts, and Google Scholar. SYNTHESIS: From a review and systematic evaluation of the available evidence, consensus guidelines on the approach to prehospital care of dogs and cats in 18 scenarios were developed. CONCLUSIONS: Due to the lack of current evidence in the veterinary prehospital arena, best practice guidelines were developed as an initial platform. Recommendations were based on a review of pertinent human and available veterinary literature as well as a consensus of the authors' professional opinions. It is anticipated that evidence-based additions will be made in the future. PMID- 26994502 TI - Quantifying and qualifying the use of topical anesthetics in retinopathy of prematurity examinations. AB - The American Academy of Pediatrics advocates efforts to minimize discomfort and systemic effect of retinopathy of prematurity (ROP) examinations. Although many ophthalmologists use topical anesthetics, many do not believe them necessary. We present the results of the first survey to quantify the use of topical anesthetics in ROP examinations by clinicians who screen for ROP. The results show that although use of topical anesthetic is common, it is not universal. PMID- 26994503 TI - Infantile-onset glaucoma and anterior megalophthalmos in osteogenesis imperfecta. AB - Osteogenesis imperfecta (OI) is an inherited condition in which defects in type 1 collagen cause abnormalities in many tissues and organs, including bone, teeth, heart valves, and eyes. We describe a 6-month-old boy with OI who presented with anterior megalophthalmos of the right eye and infantile-onset glaucoma of the left eye. To our knowledge, this is the first reported case of these types of congenital eye anomalies in an infant with OI. PMID- 26994504 TI - Association Of Bleeding Avoidance Strategies with age-related bleeding and In hospital mortality in patients undergoing percutaneous coronary Interventions. AB - BACKGROUND: The association of bleeding avoidance strategy (BAS) (consisting of a combination of radial access, bivalirudin [rather than heparin +/- glycoprotein GPIIb/IIIa antagonists], and/or vascular closure devices after femoral access) with bleeding and in-hospital outcomes has not been evaluated among elderly patients undergoing percutaneous coronary interventions (PCI). METHODS: We studied BAS use, bleeding and in-hospital mortality among 121,635 patients categorized by age (<50, 50-59, 60-69, 70-79, and >=80years) undergoing PCI from the BMC2 registry (1/2010-12/2013). RESULTS: The use of BAS decreased marginally with age and despite improved utilization over time, remained lower among the elderly. BAS was used in a much lower risk cohort among all age groups. Nonetheless, compared with no BAS, the use of this strategy was associated with lower bleeding (adjusted OR 0.984, 95% CI 0.980-0.985) and in-hospital mortality (adjusted OR 0.996, 95% CI 0.994-0.997) among all age-groups. Similar relative reduction in the risk of bleeding was observed among all age groups with BAS use with lowest risk (thus greatest absolute risk reduction given their highest risk for bleeding) for the oldest cohort. CONCLUSIONS: BAS use decreased with age among patients undergoing PCI despite its association with lower in-hospital mortality. Although overall utilization improved over time, it still remained lower in the elderly cohort, a group likely to benefit most from it. These data identified an opportunity to design strategies to improve BAS use particularly among high-risk elderly patients undergoing PCI so as to decrease bleeding and reduce related adverse events and costs. PMID- 26994505 TI - Total anomalous pulmonary venous return. PMID- 26994506 TI - Externalized biventricular implantable cardioverter-defibrillator. PMID- 26994507 TI - The human microbiota: novel targets for hospital-acquired infections and antibiotic resistance. AB - PURPOSE: Hospital-acquired infections are increasing in frequency due to multidrug resistant organisms (MDROs), and the spread of MDROs has eroded our ability to treat infections. Health care professionals cannot rely solely on traditional infection control measures and antimicrobial stewardship to prevent MDRO transmission. We review research on the microbiota as a target for infection control interventions. METHODS: We performed a literature review of key research findings related to the microbiota as a target for infection control interventions. These data are summarized and used to outline challenges, opportunities, and unanswered questions in the field. RESULTS: The healthy microbiota provides protective functions including colonization resistance, which refers to the microbiota's ability to prevent colonization and/or expansion of pathogens. Antibiotic use and other exposures in hospitalized patients are associated with disruptions of the microbiota that may reduce colonization resistance and select for antibiotic resistance. Novel methods to exploit protective mechanisms provided by an intact microbiota may provide the key to preventing the spread of MDROs in the health care setting. CONCLUSIONS: Research on the microbiota as a target for infection control has been limited. Epidemiologic studies will facilitate progress toward the goal of manipulating the microbiota for control of MDROs in the health care setting. PMID- 26994508 TI - Activity preferences, lifestyle modifications and re-injury fears influence longer-term quality of life in people with knee symptoms following anterior cruciate ligament reconstruction: a qualitative study. AB - QUESTIONS: How do people with knee symptoms describe their quality of life and experiences 5 to 20 years after anterior cruciate ligament reconstruction (ACLR)? What factors impact upon the quality of life of these people? DESIGN: Qualitative study. PARTICIPANTS: Seventeen people with knee symptoms 5 to 20 years after ACLR and high (n=8) or low (n=9) quality of life scores were recruited from a cross sectional study. METHODS: Semi-structured telephone interviews were conducted and transcribed. The data obtained from the interventions underwent inductive coding and thematic analysis. RESULTS: Four consistent themes emerged from the interviews as common determinants of quality of life following ACLR: physical activity preferences; lifestyle modifications; adaptation and acceptance; and fear of re-injury. All participants described the importance of maintaining a physically active lifestyle and the relationship between physical activity and quality of life. Participants who avoided sport or activity reported experiencing reduced quality of life. Participants who suppressed or overcame re-injury fears to continue sport participation described experiencing a satisfactory quality of life while taking part in sport despite knee symptoms. For some participants, resuming competitive sport resulted in subsequent knee trauma, anterior cruciate ligament re-rupture or progressive deterioration of knee function, with negative impacts on quality of life following sport cessation. Participants who enjoyed recreational exercise often adapted their lifestyle early after ACLR, while others described adapting their lifestyle at a later stage to accommodate knee impairments; this was associated with feelings of acceptance and satisfaction, irrespective of knee symptoms. CONCLUSION: Activity preferences, lifestyle modifications and fear of re-injury influenced quality of life in people with knee symptoms up to 20 years following ACLR. People with a preference for competitive sport who do not enjoy recreational exercise might be at heightened risk of poor quality of life outcomes and could benefit from support to facilitate a transition to a physically active, satisfying lifestyle. PMID- 26994509 TI - Re-Emergence of Zika Virus: A Review on Pathogenesis, Clinical Manifestations, Diagnosis, Treatment, and Prevention. AB - Zika virus (ZKV) is an arbovirus of the Flaviviridae family, which includes West Nile, dengue fever, yellow fever, and Japanese encephalitis virus. It is transmitted by the Aedes genus of mosquitoes. Before 2015, ZKV outbreaks occurred in areas of Africa, the Pacific Islands, and Southeast Asia. The current large outbreak, which began in Brazil, has also emerged throughout a large part of South/Central America, a number of islands in the Caribbean, including Puerto Rico, the Virgin Islands, and Mexico. A sudden rise in the numbers of infants reported born with microcephaly in Brazil, and the detection of the single stranded positive RNA virus in the amniotic fluid of affected newborns, has captured medical, mainstream media, and global political attention, causing considerable concern in a post-Ebola global community considerably more focused on the threat of internationally transmissible diseases. The goal of this article is to provide an overview of ZKV for clinicians, with the emphasis on pathogenesis, clinical manifestations, diagnosis, and treatment/preventive measures. PMID- 26994510 TI - Mortality in Patients with Atrial Fibrillation Randomized to Edoxaban or Warfarin: Insights from the ENGAGE AF-TIMI 48 Trial. AB - BACKGROUND: When compared with warfarin, edoxaban significantly reduced cardiovascular mortality in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial. We studied the possible reasons leading to this reduction. METHODS: ENGAGE AF-TIMI 48 was a double-blind, double-dummy comparison of warfarin with 2 regimens of once-daily edoxaban in 21,105 patients with atrial fibrillation followed for 2.8 years (median). Causes of deaths in the intention to-treat population were classified as cardiovascular (including fatal bleeding and ischemic stroke), malignancy, or noncardiovascular/nonmalignancy by an independent, blinded, clinical endpoint committee. Deaths also were adjudicated as directly due to bleeding (ie, fatal), or bleeding contributing to death, or neither. RESULTS: There were 839 total deaths (4.35%/y) in the warfarin arm, compared with 773 (3.99%/y, P = .08) with the higher-dose edoxaban regimen, and 737 (3.80%/y, P = .006) with the lower-dose edoxaban regimen. No significant differences between treatments were observed in (1) any of the 3 most common causes of cardiovascular death (sudden cardiac, heart failure, ischemic stroke), (2) fatal malignancies, (3) other noncardiovascular death. There were 124 fatal bleeds, 65 with warfarin, significantly fewer with the higher-dose (n = 35, P = .003) and lower-dose (n = 24, P < .001) edoxaban regimens. There were 101 bleeding events with warfarin that were either fatal or that contributed to death. There were significantly fewer with the higher-dose (n = 59, P = .001) and lower-dose (n = 54, P < .001) edoxaban regimens. CONCLUSIONS: Fewer total and cardiovascular deaths were observed with edoxaban as compared with warfarin in the ENGAGE AF-TIMI 48 trial, and this predominantly resulted from the significantly lower rate of major bleeding with edoxaban. Edoxaban reduces mortality both directly (less fatal bleeding) and indirectly (fewer bleeding related complications and interruptions in therapy after nonfatal bleeding). PMID- 26994512 TI - PDX1 and ISL1 differentially coordinate with epigenetic modifications to regulate insulin gene expression in varied glucose concentrations. AB - The mechanism of insulin gene transcription control in response to glucose concentration is poorly defined. The islet-restricted transcription factors PDX1 and ISL1 interact with BETA2, activating insulin gene expression. However, their contribution and hierarchical organization in insulin expression control based on glucose concentration remain unknown. We investigated PDX1 and ISL1 regulation of insulin gene expression in pancreatic beta cells cultured in normal (5 mM/L) and high (25 mM/L) glucose conditions. ISL1 interacted with BETA2 to maintain basic insulin gene transcriptional activity under normal glucose. The ISL1-recruited cofactors SET9 and JMJD3 facilitated insulin gene histone modifications under normal glucose. In high-glucose concentrations, PDX1 formed a complex with BETA2 to enhance insulin gene expression. PDX1 also recruited SET9 and JMJD3 to promote the activation of histone modulation on the insulin promoter. This is the first evidence transcription factors orchestrate epigenetic modifications to control insulin gene expression based on glucose concentration. PMID- 26994513 TI - Effect of glucocorticoids on the activity, expression and proximal promoter of type II deiodinase in rat brown adipocytes. AB - Triiodothyronine (T3) is important for thermogenesis in brown adipose tissue (BAT). Type II deiodinase (DIO2) produces T3 required for intracellular needs in BAT. Brown adipocytes in culture require T3 for the adrenergic stimulation of DIO2. Glucocorticoids induce adipocyte differentiation (lipogenesis). We investigated the regulation of DIO2 activity, Dio2 mRNA and Dio2 promoter activity by glucocorticoids in primary cultures of rat brown adipocytes using dexamethasone (DEX) and hydrocortisone (HC). DEX and HC regulated the adrenergic stimulation of DIO2 activity in a dose- and time-dependent manner, inhibiting DIO2 activity at short treatment times and large doses (1-10 MUM) and stimulating DIO2 at low HC doses (1-100 nM) and longer times (DEX). Insulin depletion reduced DIO2 activity but the response to glucocorticoids remained unchanged. DEX and HC inhibited basal DIO2 activity. DEX had no effect on DIO2 half-life, whereas HC stabilized DIO2 activity. DEX and HC inhibited the adrenergic stimulation of Dio2 mRNA expression (100-10000 nM, 14-96 h), but stabilized Dio2 mRNA, particularly DEX. DEX increased basal Dio2 mRNA levels, possibly through stabilization of Dio2 mRNA. An 807 bp construct of the murine Dio2 proximal promoter showed maximal reporter activity, with the cAMP response element (CRE) essential for transcriptional activity. DEX caused inhibition in most constructs containing the CRE element whereas HC stimulated reporter activity in the 807 bp construct. Glucocorticoids inhibited the adrenergic stimulation of Dio2 at the transcriptional level in brown adipocytes, although DIO2 activity increased with HC, possibly due to stabilization of Dio2 activity and mRNA. The CRE and cEBP elements of the Dio2 promoter seem involved in the regulation by glucocorticoids. PMID- 26994511 TI - Impact of placental insufficiency on fetal skeletal muscle growth. AB - Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal "catch-up" growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID- 26994514 TI - IGF1-R inhibition and liposomal doxorubicin: Progress in preclinical evaluation for the treatment of adrenocortical carcinoma. AB - Adrenocortical carcinoma (ACC) is a tumor with poor prognosis and limited therapeutic options. Therefore, in addition to multi-chemotherapeutic regimens IGF-1 receptor (IGF-1R) targeting approaches have been evaluated including immunoliposomal (IL) preparations utilizing an IGF-1R inhibiting antibody. In the current study, we extended our experiments by long-term treatment regimens in the classical adrenocortical NCIH295R xenograft model as well as by short-term experiments in two novel xenograft models, which all displayed different levels of IGF-1R and IGF-2 expression. Interestingly, these experiments reveal sub-group dependent differences in therapeutic outcome, reflecting clinical observations and indicate, thus, that implementation of this panel of tumor models might be helpful for clinical translation of novel therapeutic regimens in the future. PMID- 26994515 TI - Naringenin-induced migration of embrynoic trophectoderm cells is mediated via PI3K/AKT and ERK1/2 MAPK signaling cascades. AB - For successful pregnancy, a well-coordinated network of growth factors, nutrients and hormones is required for fetal-maternal interactions. Naringenin, as a weak phytoestrogen, improves diabetes, inflammation, neuronal diseases, cardiovascular diseases and cancers. However, the role of naringenin in migration mechanism(s) of peri-implantation conceptuses is unknown. Therefore, in the present study, we determined the effects of naringenin on migration of porcine trophectoderm (pTr) cells, which is a known in vitro model for research on trophectoderm cell biology and placental-fetal developmental biology, in order to assess intracellular signal transduction pathways activated by naringenin. Migration of pTr cells increased in a dose-dependent manner in response to naringenin. Also, naringenin activated the phosphorylation of AKT and ERK1/2 proteins in a dose-dependent manner and those proteins were abundant mainly in the cytoplasm of naringenin treated pTr cells. Within 30 min after treatment with 20 MUM naringenin, the abundance of phosphorylated EKR1/2, P70S6K, P90RSK and S6K proteins increased, and then returned to basal levels by 120 min whereas the abundance of AKT increased gradually to 120 min post-treatment. However, the phosphorylation of AKT, P70S6K, P90RSK and S6K was reduced in naringenin-induced pTr cells pre treated with a PI3K inhibitor (LY294002). Also, a MEK1/2 inhibitor (U0126) significantly decreased naringenin-induced phosphorylation of ERK1/2, P70S6K and S6K proteins in pTr cells. Moreover, the naringenin-stimulated migration of pTr cells was suppressed by LY294002 and U0126. Collectively, results of the present study suggest that naringenin supports migration of pTr cells through PI3K/AKT and ERK1/2 MAPK signaling pathways crucial for orchestrating conceptus-uterine interactions. PMID- 26994516 TI - Efficacy and safety of a novel oral isoxazoline, sarolaner (SimparicaTM) in the treatment of naturally occurring flea and tick infestations in dogs presented as veterinary patients in Europe. AB - Two randomised, blinded, multi-centered field studies were conducted in Europe to demonstrate the efficacy and safety of three monthly oral doses of sarolaner (SimparicaTM, Zoetis) administered at a minimum dosage of 2.0mg/kg (range 2 4mg/kg) against natural flea or tick infestation of dogs presented as veterinary patients. In the flea study, the improvement in clinical signs associated with flea allergy dermatitis (FAD) was also investigated. The palatability of the sarolaner chewable tablet formulation was evaluated in both studies. Spinosad (Comfortis((r)) Chewable Tablets, Elanco) and fipronil (Frontline((r)) Spot on, Merial) were used as positive controls in the flea and tick study, respectively. Treatments were administered on Days 0, 30 and 60. Efficacy was calculated based on the mean percent reduction of live parasite counts on post-treatment days 14, 30, 60 and 90 versus the pre-treatment count on Day 0. Non-inferiority of sarolaner to the control products was assessed at each time-point using a margin of 15% at the one-sided 0.025 significance level. Dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 285 flea- and 181 tick-infested dogs were assessed for efficacy and safety, and 137 and 48 dogs were assessed for safety only, in the flea and tick study, respectively. There were no treatment-related adverse events. Efficacy against fleas was 98.8%, 99.4%, >99.9% and >99.9% in the sarolaner-treated group and 98.9%, 93.7%, 96.8% and 95.1% in the spinosad-treated group on Days 14, 30, 60 and 90, respectively. Sarolaner was non-inferior to spinosad at all time-points and was superior on Day 30. For the 42 dogs identified as having FAD at enrolment, the clinical signs of FAD improved in all dogs and the incidence was markedly reduced by the end of the study. Efficacy against ticks was 97.4%, 97.6%, 99.8% and 100% in the sarolaner-treated group and 94.1%, 88.5%, 89.9% and 98.1% in the fipronil-treated group on Days 14, 30, 60 and 90, respectively. Sarolaner was non-inferior to fipronil at all time-points, and was superior on Days 30 and 60. Sarolaner tablets were voluntarily and fully consumed within one minute in 93% of the 1280 occasions offered. Sarolaner administered orally at monthly intervals at a minimum dosage of 2 mg/kg was safe and highly effective against natural infestations of fleas and ticks on dogs. In addition, clinical signs FAD improved in dogs treated with sarolaner, and the flavored, chewable tablets were highly palatable. PMID- 26994517 TI - Does perceived injustice correlate with pain intensity and disability in orthopaedic trauma patients? AB - INTRODUCTION: Individuals who experience musculoskeletal trauma may construe the experience as unjust and themselves as victims. Perceived injustice is a cognitive construct comprised by negative appraisals of the severity of loss as a consequence of injury, blame, injury-related loss, and unfairness. It has been associated with worse physical and psychological outcomes in the context of chronic health conditions. The purpose of this study is to explore the association of perceived injustice to pain intensity and physical function in patients with orthopaedic trauma. METHODS: A total of 124 orthopaedic trauma patients completed the Injustice Experience Questionnaire (IEQ), the PROMIS Physical Function Computer Adaptive Testing (CAT), the PROMIS Pain Intensity instruments, the short form Patient Health Questionnaire for depression (PHQ-2), the short form Pain Self-Efficacy Questionnaire (PSEQ-2), and the short form Pain Catastrophizing Scale (PCS-4) on a tablet computer. A stepwise linear regression model was used to identify the best combination of predictors explaining variance in PROMIS Physical Function and PROMIS Pain Intensity. RESULTS: The IEQ was associated with PROMIS Physical Function (r=-0.36; P<0.001) and PROMIS Pain Intensity (r=0.43; P<0.001). In multivariable analysis, however, Caucasian race (beta=5.1, SE: 2.0, P=0.013, 95% CI: 1.1-9.2), employed work status (beta=5.1, SE: 1.5, P=0.001, 95% CI: 2.1-8.2), any cause of injury other than sports, mvc, or fall (beta=7.7, SE: 2.1, P<0.001, 95% CI: 3.5-12), and higher self-efficacy (PSEQ-2; beta=0.93, SE: 0.23, P<0.001, 95% CI: 0.48-1.4) were selected as part of the best model predicting variance in PROMIS Physical Function. Only a higher degree of catastrophic thinking (PCS-4; beta=1.2, SE: 0.12, P<0.001, 95% CI: 0.99 to 1.5) was selected as important in predicting higher PROMIS Pain Intensity. CONCLUSION: Perceived injustice was associated with both physical function and pain intensity in bivariate correlations, but was not deemed as an important predictor when assessed along with other demographic and psychosocial variables in multivariable analysis. This study confirms prior research on the pivotal role of catastrophic thinking and self-efficacy in reports of pain intensity and physical function in patients with acute traumatic musculoskeletal pain. PMID- 26994518 TI - Complications associated with operative fixation of acute midshaft clavicle fractures. AB - INTRODUCTION: The aim of this study was to review the complication rate and profile associated with surgical fixation of acute midshaft clavicle fracture in a large cohort of patients treated in a level I trauma centre. PATIENTS AND METHODS: We identified all patients who underwent surgical treatment of acute midshaft clavicle fracture between 2002 and 2010. The study group consisted of 138 fractures (134 patients) and included 107 men (78%) and 31 women (22%); the median age of 35 years (interquartile range (IQR) 24-45). The most common mechanism of injury was a road traffic accident (78%). Sixty percent (n=83) had an injury severity score of >=15 indicating major trauma. The most common fracture type (75%) was simple or wedge comminuted (2B1) according to the Edinburgh classification. The median interval between the injury and operation was 3 days (IQR 1-6). Plate fixation was performed in 110 fractures (80%) and intramedullary fixation was performed in 28 fractures (20%). There were 85 men and 25 women in the plate fixation group with median age of 35 years (IQR 25-45) There were 22 men and six women in the intramedullary fixation group with median age of 31 years (IQR 24-42 years). Statistical analysis was performed using independent sample t test, Mann Whitney test, and Chi square test. Significant P value was <0.05. RESULTS: The overall incidence of complication was 14.5% (n=20). The overall nonunion rate was 6%. Postoperative wound infection occurred in 3.6% of cases. The incidence of complication associated with plate fixation was 10% (11 of 110 cases) compared to 32% associated with intramedullary fixation (nine of 28 cases; P=0.003). Thirty-five percent of complications were related to inadequate surgical technique and were potentially avoidable. Symptomatic hardware requiring removal occurred in 23% (n=31) of patients. Symptomatic metalware was more frequent after plate fixation compared to intramedullary fixation (26% vs 7%, P=0.03). CONCLUSIONS: Intramedullary fixation of midshaft clavicle fracture is associated with a higher incidence of complications. Plate fixation is associated with a higher rate of symptomatic metalware requiring removal compared to intramedullary fixation. Approximately one in three complications may be avoided by attention to adequate surgical technique. PMID- 26994519 TI - Pre-operative labs: Wasted dollars or predictors of post-operative cardiac and septic events in orthopaedic trauma patients? AB - PURPOSE: As US healthcare expenditures continue to rise, there is significant pressure to reduce the cost of inpatient medical services. Studies have estimated that over 70% of routine labs may not yield clinical benefits while adding over $300 in costs per day for every inpatient. Although orthopaedic trauma patients tend to have longer inpatient stays and hip fractures have been associated with significant morbidity, there is a dearth of data examining pre-operative labs in predicting post-operative adverse events in these populations. The purpose of this study was to assess whether pre-operative labs significantly predict post operative cardiac and septic complications in orthopaedic trauma and hip fracture patients. METHODS: Between 2006 and 2013, 56,336 (15.6%) orthopaedic trauma patients were identified and 27,441 patients (7.6%) were diagnosed with hip fractures. Pre-operative labs included sodium, BUN, creatinine, albumin, bilirubin, SGOT, alkaline phosphatase, white count, hematocrit, platelet count, prothrombin time, INR, and partial thromboplastin time. For each of these labs, patients were deemed to have normal or abnormal values. Patients were noted to have developed cardiac or septic complications if they sustained (1) myocardial infarction (MI), (2) cardiac arrest, or (3) septic shock within 30 days after surgery. Separate regressions incorporating over 40 patient characteristics including age, gender, pre-operative comorbidities, and labs were performed for orthopaedic trauma patients in order to determine whether pre-operative labs predicted adverse cardiac or septic outcomes. RESULTS: 749 (1.3%) orthopaedic trauma patients developed cardiac complications and 311 (0.6%) developed septic shock. Multivariate regression demonstrated that abnormal pre-operative platelet values were significantly predictive of post-operative cardiac arrest (OR: 11.107, p=0.036), and abnormal bilirubin levels were predictive (OR: 8.487, p=0.008) of the development of septic shock in trauma patients. In the hip fracture cohort, abnormal partial thromboplastin time was significantly associated with post-operative myocardial infarction (OR: 15.083, p=0.046), and abnormal bilirubin (OR: 58.674, p=0.002) significantly predicted the onset of septic shock. CONCLUSIONS: This is the first study to demonstrate the utility of pre-operative labs in predicting perioperative cardiac and septic adverse events in orthopaedic trauma and hip fracture patients. Particular attention should be paid to haematologic/coagulation labs (platelets, PTT) and bilirubin values. LEVEL OF EVIDENCE: Prognostic Level II. PMID- 26994520 TI - Surgical outcomes of temporary short-segment instrumentation without augmentation for thoracolumbar burst fractures. AB - BACKGROUND: Short-segment posterior spinal instrumentation for thoracolumbar burst fracture provides superior correction of kyphosis by an indirect reduction technique, but it has a high failure rate. We investigated the clinical and radiological results of temporary short-segment pedicle screw fixation without augmentation performed for thoracolumbar burst fractures with the goal of avoiding treatment failure by waiting to see if anterior reconstruction was necessary. METHODS: We studied 27 consecutive patients with thoracolumbar burst fracture who underwent short-segment posterior instrumentation using ligamentotaxis with Schanz screws and without augmentation. Implants were removed approximately 1 year after surgery. Neurological function, kyphotic deformity, canal compromise, fracture severity, and back pain were evaluated prospectively. RESULTS: After surgery, all patients with neurological deficit had improvement equivalent to at least 1 grade on the American Spinal Injury Association impairment scale and had fracture union. Kyphotic deformity was reduced significantly, and maintenance of the reduced vertebra was successful even without vertebroplasty, regardless of load-sharing classification. Therefore, no patients required additional anterior reconstruction. Postoperative correction loss occurred because of disc degeneration, especially after implant removal. Ten patients had increasing back pain, and there are some correlations between the progression of kyphosis and back pain aggravation. CONCLUSION: Temporary short segment fixation without augmentation yielded satisfactory results in reduction and maintenance of fractured vertebrae, and maintenance was independent of load sharing classification. Kyphotic change was caused by loss of disc height mostly after implant removal. Such change might have been inevitable because adjacent endplates can be injured during the original spinal trauma. Kyphotic change after implant removal may thus be a limitation of this surgical procedure. PMID- 26994521 TI - Subcellular localization of five singular WSC domain-containing proteins and their roles in Beauveria bassiana responses to stress cues and metal ions. AB - Some model fungi have three or four proteins with each vectoring a single cell Wall Stress-responsive Component (WSC) domain at N-terminus. In this study, five proteins, each vectoring only a single WSC domain in N-terminal, central or even C-terminal region, were found in Beauveria bassiana, a filamentous fungal entomopathogen, and named Wsc1A-1E due to the domain singularity. Four of them lack either transmembrane domain or C-terminal conserved signature sequence (DXXD) compared with the homologues in the model fungi. Intriguingly, all the eGFP-tagged fusion proteins of Wsc1A-1E were evidently localized to the cell wall and membrane of transgenic hyphae. Single deletions of the five wsc genes resulted in significant, but differential, increases in cellular sensitivity to cell wall perturbation, oxidation, high osmolarity, and four to six metal ions (Zn(2+) , Mg(2+) , Fe(2+) , K(+) , Ca(2+) and Mn(2+) ). Each deletion mutant also showed a delay of germination and a decrease of conidial UV-B resistance, thermotolerance or both. However, none of the deletions affected substantially the fungal growth, conidiation and virulence. Our results indicate a significance of each WSC protein for the B. bassiana adaptation to diverse habitats of host insects. PMID- 26994522 TI - Web Alert: Endophytic microbes. PMID- 26994523 TI - Hydroxyl-modified magnetite nanoparticles as novel carrier for delivery of methotrexate. AB - In this work, novel hydroxyl-modified magnetite nanocarriers are introduced as efficient host for methotrexate conjugation. The modification was based on the Micheal type addition reaction between tris(hydroxymethyl) aminomethane and acrylamidopropyl functionalized, silica-coated magnetite nanoparticle. The chemical structure characterization was carried out by FT-IR and the organic content was determined by CHN analysis. The topography was studied by SEM, TEM, AFM. DLS was performed to show particles' mean diameter. Furthermore, the magnetite properties of modified particles were evaluated by VSM and the crystallinity was proved by XRD. To illustrate the efficiency of the modified particles, the anti-cancer drug methotrexate was conjugated to hydroxyl groups through estric bond formation. The controlled release activity of established nanoparticles was evaluated in simulated cellular fluid. Later, the anti-cancer behavior of drug conjugated nanoparticles was evaluated in vitro in MCF-7 cell line which showed enhanced toxicity after 48 h. Conclusively, the modified nanoparticles have remarked as powerful carrier to be applied as an anti-cancer agent. PMID- 26994524 TI - External digital pressure to enable a deeper tulip-bundle technique for endoscopic closure of a refractory chronic gastrocutaneous fistula. PMID- 26994525 TI - Spontaneous regression of hepatocellular carcinoma. A case report. PMID- 26994526 TI - Measuring time during early embryonic development. AB - In most metazoans, embryonic development is orchestrated by a precise series of cellular behaviors. Understanding how such events are regulated to achieve a stereotypical temporal progression is a fundamental problem in developmental biology. In this review, we argue that studying the regulation of the cell cycle in early embryonic development will reveal novel principles of how embryos accurately measure time. We will discuss the strategies that have emerged from studying early development of Drosophila embryos. By comparing the development of flies to that of other metazoans, we will highlight both conserved and alternative mechanisms to generate precision during embryonic development. PMID- 26994527 TI - X inactivation and reactivation in X-linked diseases. AB - X chromosome inactivation (XCI) is the phenomenon by which mammals compensate for dosage of X-linked genes in females (XX) versus males (XY). XCI patterns can be random or show extreme skewing, and can modify the mode of inheritance of X driven phenotypes, which contributes to the variability of human pathologies. Recent findings have shown reversibility of the XCI process, which has opened new avenues in the approaches used for the treatment of X-linked diseases. PMID- 26994528 TI - Tissue morphodynamics: Translating planar polarity cues into polarized cell behaviors. AB - The ability of cells to collectively orient and align their behaviors is essential in multicellular organisms for unidirectional cilia beating, collective cell movements, oriented cell divisions, and asymmetric cell fate specification. The planar cell polarity pathway coordinates a vast and diverse array of collective cell behaviors by intersecting with downstream pathways that regulate cytoskeletal dynamics and intercellular signaling. How the planar polarity pathway translates directional cues to produce polarized cell behaviors is the focus of this review. PMID- 26994529 TI - Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking. AB - We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n=917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID- 26994531 TI - Chicken bone as swallowed foreign body. PMID- 26994530 TI - Genetic polymorphisms of interleukin-22 in patients with ulcerative colitis. AB - BACKGROUND: Ulcerative colitis (UC) is a multifactorial and polygenic disease. Interleukin-22 (IL-22) is an immunomodulatory cytokine that belongs to the IL-10 family. Currently, some IL-22 polymorphisms have been associated with inflammatory processes such as rheumatoid arthritis and psoriasis vulgaris, but there are no studies on UC. AIM: The aim of this work was to study the frequency of polymorphisms of IL-22 in Mexican patients with UC. METHODS: We studied a total of 199 Mexican patients with confirmed UC and 697 healthy controls. All individuals were born in Mexico, at least three family generations earlier. A blood sample was obtained from the UC patients and healthy controls in order to perform DNA extraction and then to determine the frequency of IL-22 polymorphisms (rs2227485, rs2272478, rs2227491). RESULTS: No statistical significance was found in the gene and genotype frequencies of three SNPs of IL-22 (rs2227485, rs2272478, rs2227491) between the UC patients and healthy controls. No association was found between those IL-22 SNPs and clinical features of UC. CONCLUSIONS: There was no association between IL-22 SNPs (rs2227485, rs2272478, rs2227491) and the development of UC in a Mexican population. PMID- 26994532 TI - Sharp thinking. PMID- 26994533 TI - The Difficult Airway Society 2015 guidelines and the sacred cows of routine airway management. PMID- 26994534 TI - Difficult Airway Society guidelines 2015: what about the anticipated difficult airway? PMID- 26994535 TI - The 2015 Difficult Airway Society guidelines: what about the anticipated difficult airway? A reply. PMID- 26994536 TI - Design quality or infection control? PMID- 26994537 TI - AAGBI recommendations for standards of monitoring during anaesthesia and recovery 2015. PMID- 26994538 TI - Potential for conduction of microshock via intravenous fluids--manufacturer's reply. PMID- 26994539 TI - Potential for conduction of microshock via intravenous fluids. PMID- 26994540 TI - Regional anaesthesia competency assessment. PMID- 26994541 TI - Regional anaesthesia assessment tools--a reply. PMID- 26994542 TI - Draw-over or push over during manual ventilation with the Tri-Service Anaesthetics Apparatus? PMID- 26994543 TI - Tranexamic acid, hip replacement and starch. PMID- 26994544 TI - Tranexamic acid, hip replacement and starch--a reply. PMID- 26994545 TI - Sensing injection pressure: the Jedi grip clarified. PMID- 26994546 TI - Fixing endotracheal tubes in patients with an absent lingual frenulum. PMID- 26994547 TI - Reversing non-depolarising muscle relaxants, nausea and residual curarisation. PMID- 26994548 TI - Correction. AB - Sukcharanjit S, Tan AS, Loo AV, Chan XL, Wang CY. The effect of a forced-air warming blanket on patients' end-tidal and transcutaneous carbon dioxide partial pressures during eye surgery under local anaesthesia: a single-blind, randomised controlled trial. Anaesthesia 2015; 70: 1390-4. In the article [1] by Sukcharanjit et al., data in the 'Systolic blood pressure; mmHg' row in Table 1 is listed incorrectly. It should be: 158.0 (14.3) in the Forced air warmer column and 160.9 (15.6) in the Heated Overblanket column. PMID- 26994549 TI - Computational analysis of the CB1 carboxyl-terminus in the receptor-G protein complex. AB - Despite the important role of the carboxyl-terminus (Ct) of the activated brain cannabinoid receptor one (CB1) in the regulation of G protein signaling, a structural understanding of interactions with G proteins is lacking. This is largely due to the highly flexible nature of the CB1 Ct that dynamically adapts its conformation to the presence of G proteins. In the present study, we explored how the CB1 Ct can interact with the G protein by building on our prior modeling of the CB1-Gi complex (Shim, Ahn, and Kendall, The Journal of Biological Chemistry 2013;288:32449-32465) to incorporate a complete CB1 Ct (Glu416(Ct) Leu472(Ct)). Based on the structural constraints from NMR studies, we employed ROSETTA to predict tertiary folds, ZDOCK to predict docking orientation, and molecular dynamics (MD) simulations to obtain two distinct plausible models of CB1 Ct in the CB1-Gi complex. The resulting models were consistent with the NMR determined helical structure (H9) in the middle region of the CB1 Ct. The CB1 Ct directly interacted with both Galpha and Gbeta and stabilized the receptor at the Gi interface. The results of site-directed mutagenesis studies of Glu416(Ct), Asp423(Ct), Asp428(Ct), and Arg444(Ct) of CB1 Ct suggested that the CB1 Ct can influence receptor-G protein coupling by stabilizing the receptor at the Gi interface. This research provided, for the first time, models of the CB1 Ct in contact with the G protein. PMID- 26994550 TI - Ensemble models of proteins and protein domains based on distance distribution restraints. AB - Conformational ensembles of intrinsically disordered peptide chains are not fully determined by experimental observations. Uncertainty due to lack of experimental restraints and due to intrinsic disorder can be distinguished if distance distributions restraints are available. Such restraints can be obtained from pulsed dipolar electron paramagnetic resonance (EPR) spectroscopy applied to pairs of spin labels. Here, we introduce a Monte Carlo approach for generating conformational ensembles that are consistent with a set of distance distribution restraints, backbone dihedral angle statistics in known protein structures, and optionally, secondary structure propensities or membrane immersion depths. The approach is tested with simulated restraints for a terminal and an internal loop and for a protein with 69 residues by using sets of sparse restraints for underlying well-defined conformations and for published ensembles of a premolten globule-like and a coil-like intrinsically disordered protein. PMID- 26994551 TI - Comprehensive analysis of 61 characteristic constituents from Siraitiae fructus using ultrahigh-pressure liquid chromatography with time-of-flight mass spectrometry. AB - A systematic method was established for the qualitative and quantitative analysis of characteristic components such as triterpenoids and flavonols in Siraitiae fructus, a famous antidiabetic traditional Chinese medicine (TCM). For qualitative analysis, 61 characteristic components were identified using the ultra-high performance liquid chromatography coupled with photo-diode array and quadrupole/time-of-flight mass spectrometry (UPLC-PDA-QTOF-MS/MS) based on a multiple product ions filtering (mPIF) strategy, of which 22 compounds were characterized for the first time from Siraitiae fructus. For quantitative detection, a relative quantitation assay using an extract ion chromatogram (EIC) of the full scan MS experiment was validated and employed to assess the quantity of the 61 identified compounds in 40 batches Siraitiae fructus samples from different sources. Additionally, the principal component analysis (PCA) indicated that 40 samples could be clustered into four groups and the cultivated variety was an important factor for sample classification. The methods used in present study might be also valuable for simultaneous investigation of multiple components from Siraitiae fructus for the purpose of holistic quality control, phytochemistry and metabolic studies. PMID- 26994552 TI - Elemental fingerprinting of Hypericum perforatum (St John's Wort) herb and preparations using ICP-OES and chemometrics. AB - St. John's wort (SJW) (Hypericum perforatum) is a herbal remedy commonly used to treat mild depression. The elemental profiles of 54 samples (i.e., dry herbs, tablets and capsules) were evaluated by monitoring 25 elements using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The major elemental constituents in the SJW samples were Ca (300-199,000MUg/g), Mg (410-3,530MUg/g), Al (4.4-900MUg/g), Fe (1.154-760MUg/g), Mn (2.4-261MUg/g), Sr (0.88-83.6MUg/g), and Zn (7-64MUg/g). For the sixteen elements that could be reliably quantified, principal component analysis (PCA) was used to investigate underlying patterns in the data. PCA models identified 7 key elements (i.e., Ba, Ca, Cd, Mg, Mo, Ni and Y), which described 85% of the variance in the dataset in the first three principal components. The PCA approach resulted in a general delineation between the three different formulations and provides a basis for monitoring product quality in this manner. PMID- 26994553 TI - Cervical myelomeningocele associated with multiple spinal anomalies. PMID- 26994554 TI - A new method for the separation and purification of the osteogenic compounds of nacre Ethanol Soluble Matrix. AB - Nacre is able to induce bone-forming cells mineralization, and gains widely interest in bone regeneration. While, the osteoinductive compounds are not yet identified. ESM (Ethanol Soluble Matrix), a nacre extract from powder of Pinctada margaritifera pearl oyster shell, has been firstly proven having the capacity to induce mineralization and to restore mineralization defect in vitro. It is suitable to treat ESM as a source of osteoinductive compounds. Herein, we develop a new method for separating and purifying nacre extracts by an ionic approach. At first, cationic ESM (ESMc) and anionic ESM (ESMa) were achieved with ion-exchange resin. Then, ESM was separated and collected on cation exchange HPLC. Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectrometry (EDS) was used to reveal the concentrated elements in ESM fractions. A coupled cell models were used to test the ESM fractions. Alizarin Red staining was performed and quantified to evaluate the mineralization level. ESMc and 2 HPLC fractions stimulated the mineralization in both cells. EDS demonstrated the abundant presence of calcium and chloride in the osteogenic fractions. To validate, pure CaCl2 was tested and proven having an osteogenic effect in both cells, but less stable than ESM. The mineralization nodules induced by ESM fractions and CaCl2 differed in both cells. In conclusion, a new method was developed for separating and purifying nacre extracts by an ionic approach. By which, the osteoinductive compounds in ESM were proven cationic, and calcium in ESM was demonstrated to play a role in inducing the cell mineralization. PMID- 26994555 TI - Distribution pattern and the risks of OPCs, PHAs and PCBs in aged refuses from landfill. AB - Persistent organic pollutants (POPs) are the urgent risk for landfill, and should be considered before the landfill reclamation and resource. In this work, the distribution pattern of selected POPs in landfill and their ecological risks were investigated and assessed. The Sigma20OCPs, Sigma16PAHs and Sigma19PCBs were around 157.4-329.2, 4103-19,190, and 79.1-340.3MUgkg(-1) in aged refuses, with the mean value of 206.6, 8645.4, and 155.1MUgkg(-1). While those in soil covers were only 6.3-75.4, 125.5-515.3 and 2.6-43.4MUgkg(-1), with the mean value of 33.7, 257.7, and 24.0MUgkg(-1), respectively. The maximum OPCs, PHAs and PCBs were in aged refuse with 13, 7, 10 disposal years. Whereas, the corresponding top content in soil covers were in 10, 13 and 16years, meaning that aged refuses were not the direct source for soil covers. Among 20 OCPs measured, alpha-HCH, delta HCH, Dieldrin, and Endrin were presented in all aged refuses, with the mean concentration of 93.6, 52.1, 3.9 and 4.7MUgkg(-1), respectively. For PAHs, PHE, FLU and PYR were the main composition, and reached to 1535, 1224, 1187MUgkg(-1). The Sigma7CarPAHs occupied around 33.3-49.9% of total Sigma16PAHs tested, and could be used as the indictor for PAHs pollutant in landfill. PCB-5 content was around 40.7-263.3MUgkg(-1) in aged refuses, and occupied around 51.5-81.8% of Sigma19PCBs measured. The HCHs and DDTs in aged refuses were below the national standard GB15618-1995, and the corresponding Sigma19PCBs concentrations met the standard of GB 13015-91, suggesting that aged refuse are accepted for the further utilization process. PMID- 26994556 TI - Determination of N-acetyl-beta-hexosaminidase in serum from hemolyzed blood. AB - BACKGROUND: Determination of lysosomal N-acetyl-beta-hexosaminidase (HEX) in serum from hemolyzed blood, creates serious analytical problems, because hemoglobin absorbs light at a similar wavelength like 4-nitrophenol, which is released from artificial substrate. OBJECTIVE: The objective of the work was to adapt a manual method to allow analysis of HEX in hemolyzed samples. METHODS: Serums without and with hemolysis were incubated with 4-nitrophenol-N acetylglucosamine as a substrate. Released 4-nitrophenol was determined colorimetrically. After the incubation of the serum from hemolyzed blood with substrate, hemoglobin was precipitated with trichloroacetic acid (TCA) before 4 nitrophenol determination. RESULTS: The mean concentration of HEX activity in non hemolyzed and hemolyzed blood of the same patients, determined with non-modified and modified methods had no significant differences, and they are: 243.12+/ 119.76 and 233.99+/-108.76pkat/mL, respectively. A coefficient of correlation between non-modified and modified methods equals the 0.98. For HEX determination with the modified method in serum from hemolyzed blood, optimal reaction time was 60min, pH of reaction mixture was 4.7, and Km was 0.11mMm. CONCLUSION: HEX determinations in the same serums from non-hemolyzed blood by the non-modified method and hemolyzed blood with the modified method, gave similar results with a 0.98 coefficient of correlation. The modified method is appropriate for HEX determination in serum from hemolyzed blood. PMID- 26994557 TI - Stability of specific IgE antibodies to common food and inhalant allergens. AB - OBJECTIVE: To determine the optimum storage temperature for serum allergen specific IgE antibodies (sIgE) to common food and inhalant allergens. METHODS: Patient sera with sIgE concentrations >=0.7kIUA/l were pooled accordingly: pool 1 peanut and hazelnut, pool 2-egg white, cow's milk and cod fish, pool 3-soy, wheat and shrimp and pool 4-dust mite Dermatophagoides farinae, dog dander, cat dander, Timothy grass pollen, and silver birch pollen. Aliquots stored frozen, refrigerated and at room temperature were tested in duplicate (Phadia ImmunoCAP(r) 250) over two weeks. The relative difference was calculated for each sIgE as a percentage of the initial value and compared to the analytical reference change value. RESULTS: Minimal effects on specimen stability were noted for all sIgE analyzed under the three storage conditions tested in this study. All changes observed in sIgE concentrations were related to the assay variability and not to sample deterioration. CONCLUSION: Serum allergen specific IgE concentrations are stable at all temperatures studied for up to 17days. PMID- 26994558 TI - Validation of cooling detection threshold as a marker of sensorimotor polyneuropathy in type 2 diabetes. AB - AIM: We aimed to validate the performance cooling detection thresholds (CDT) to detect diabetic sensorimotor polyneuropathy (DSP) in type 2 diabetes. METHODS: Two hundred and twenty participants with type 2 diabetes underwent clinical and electrophysiological examinations including 3 small fiber function tests: CDT, heart rate variability (HRV) and LDIFLARE. Clinical DSP was defined by consensus criteria whereas preclinical DSP was defined by presence of at least one electrophysiological abnormality. Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic curves. RESULTS: Participants were aged 63 +/- 11 years with mean HbA1c of 7.5 +/- 1.6%. The 139 (63%) clinical DSP cases had mean CDT values of 18.3 +/- 8.9 degrees C; the 52 (24%) preclinical DSP cases had 25.3 +/- 3.5 degrees C; and the 29 (13%) controls had 27.1 +/- 3.8 degrees C; (p-value<0.02 for all comparisons). For identification of clinical DSP cases, AUCCDT was 0.79 which exceeded AUCHRV (0.60, p=<0.0001) and AUCLDI FLARE (0.69, p=0.0003), optimal threshold <22.8 degrees C (64% sensitivity, 83% specificity). Preclinical DSP AUCCDT was 0.80, also exceeding the other 2 measures (p<0.02 for both comparisons), optimal threshold <=27.5 degrees C (83% sensitivity, 72% specificity). CONCLUSIONS: CDT had good diagnostic performance for identification of both clinical and preclinical neuropathy in type 2 diabetes. Its use as a non-invasive screening tool should be considered for research and clinical practice. PMID- 26994561 TI - The impact of peripheral arterial disease: A proposal for a new classification. AB - Clasically, intermittent claudication, an intermediate stage in peripheral arterial disease, has been considered as a benign condition when considering only the muscular pain on walking. In this paper our aim is to attract attention about the effects linked to ischemic pain and the oxidative injury resulting from episodes of ischemia/reperfusion. Throughout this process alterations in calcium homeostasis as well as uncontrolled generation of reactive oxygen species, in association with the mitochondrial dysfunction and inflammatory phenomena, could lead to accelerate atherosclerosis, with an increased cardiovascular risk stated by means of a reduced ankle-brachial index. Taking this idea into account we propose a possible new classification for the management of the peripheral arterial disease, combining the Fontaine and Rutherford classifications and thinking about the described systemic effects in order to change the traditional management of peripheral arterial disease. PMID- 26994559 TI - Enhanced Antitumor Activity of Monophosphate Ester Prodrugs of Gemcitabine: In Vitro and In Vivo Evaluation. AB - The prodrug strategy has been explored frequently for a number of marked drugs to obtain better pharmaceutical properties and efficacy and safety profiles. For gemcitabine, a nucleoside analog that has been used widely as a chemotherapeutic agent for the treatment of a variety of cancers, the protection of the amino group from extensive deamination and increase of permeability have been used for oral prodrug development. In the present study, several novel and proprietary monophosphate ester prodrugs of gemcitabine representing different "tail" structures were evaluated for their antiproliferation activities in various tumor cell lines. As compared to LY2334737, a prototype oral prodrug of gemcitabine, the monophosphate ester prodrugs exhibited superior in vitro antiproliferation activity. Among those, compound-3 emerged as a promising prodrug candidate. Data revealed that cellular concentrations of compound-3 were correlated well with its antiproliferation activity and its cellular uptake did not involve human equilibrative nucleoside transporter, suggesting a potential to treat gemcitabine resistant tumors. Compound-3 demonstrated equal or better antitumor efficacy after oral administration as compared to intraperitoneally injected gemcitabine. Taken together, compound-3 has the potential for further development as an orally active antitumor agent. PMID- 26994562 TI - Endovascular radiofrequency ablation. Effect on the vein diameter using the ClosureFast((r)) catheter. AB - INTRODUCTION: Endovascular radiofrequency with first generation catheters was not successful due to its technical difficulty and restrictions in veins with diameters larger than 12mm. However, using the new catheter there is not enough scientific evidence to affirm that the diameter represents a technical limitation. The aim of this study was to evaluate and compare pre and post operative venous trunks diameter, aiming at the reduction of size after 6 months with last generation catheters. METHODS: Retrospective observational and descriptive study on a cohort of patients with insufficiency of the great saphenous vein, small saphenous vein and anterior accessory vein operated on with last generation radiofrequency catheters. The diameters were evaluated in the pre and post-operative period with ultrasound. RESULTS: Between 2007 and 2014 a total of 365 ablations were performed in veins with an average diameter of 9+/-3.1mm showing a reduction of it after 6 months with a mean value of 5.2+/-0.8mm (P<.0001). Total occlusion was also observed in 100% of cases and complications such as deep vein thrombosis in 0.5% and heat-induced thrombosis in 1.1%. CONCLUSIONS: A significant reduction in venous diameter after endovascular treatment with the new ClosureFast((r)) catheters was checked, even in veins with diameters greater than 12mm. PMID- 26994563 TI - The First Demonstration of the Gyroid in a Polyoxometalate-Based Open Framework with High Proton Conductivity. AB - The fabrication of extended open frameworks with crystalline ordering on the atomic level by following peculiar mathematical geometry (e.g. Mobius band, Klein bottle, periodic minimal surfaces, etc.) is challenging, but extremely beneficial for discovering non-trivial structure-dependent properties. In light of this, we herein report the first polyoxometalate-based open framework (POM-OF) that definitely lies on the gyroid (G)-minimal surface, which was constructed by a rare pair of chiral POM enantiomers and zinc ions. Due to the presence of the proton carriers (i.e., water, Na(+) , [(Bu)4 N](+) , etc.) in the resultant gyroidal channels, with pore dimensions on the order of the quasi-mesoporous scale, this compound shows a high proton conductivity of 1.04*10(-2) S cm(-1) at a relative humidity of 75 % (80 degrees C), and also exhibits enormous potential in the application of electrochemical catalysis. PMID- 26994564 TI - Evaluation of patients' attitudes to their care during oral and maxillofacial surgical outpatient consultations: the importance of waiting times and quality of interaction between patient and doctor. AB - Knowing what patients think about their care is fundamental to the provision of an effective, quality service, and it can help to direct change and reduce costs. Much of the work in oral and maxillofacial departments concerns the treatment of outpatients, but as little is known about what they think about their care, we aimed to find out which aspects were associated with satisfaction. Consecutive patients (n=244) who attended the oral and maxillofacial outpatient department at Southampton University Hospital NHS Foundation Trust over a 7-day period were given a questionnaire to complete before and after their consultation. It included questions with Likert scale responses on environmental, procedural, and interactive aspects of the visit, and a 16-point scale to rank their priorities. A total of 187 patients (77%) completed the questionnaires. No association was found between expected (p=0.93) or actual (p=0.41) waiting times, and 90% of patients were satisfied with their visit. Seeing the doctor, having confidence in the treatment plan, being listened to, and the ability of the doctor to recognise their personal needs, were ranked as important. Environmental and procedural aspects were considered the least important. These findings may be of value in the development of services to improve patient-centred care. PMID- 26994565 TI - Towards an international database of benign salivary disease: RE: Management of obstructive salivary disorders by sialendoscopy: a systematic review. PMID- 26994567 TI - Proton pump inhibitors and chronic kidney disease: is it time to sound the alarm? AB - Proton pump inhibitors are widely used worldwide for the management of gastroesophageal reflux, but have been associated with the development of interstitial nephritis and acute kidney injury. A large observational study using data from the Atherosclerosis Risk in Communities cohort and the Geisinger Health System demonstrates an association between the use of proton pump inhibitors and chronic kidney disease. Although the study does not prove causality, the robustness of the findings in two cohorts suggests a need for further study and reevaluation of the safety of these agents for widespread, non-prescription use. PMID- 26994568 TI - Precision medicine comes of age in nephrology: identification of novel biomarkers and therapeutic targets for chronic kidney disease. AB - The goal of "precision medicine" is to characterize diseases based on the underlying molecular biology, in order to identify specific biomarkers and therapeutic targets that will ultimately improve clinical outcomes. The nephrology research community has developed a strong foundation for precision medicine, and recent publications demonstrate the feasibility of this approach to identify potential biomarkers and therapeutic targets in chronic kidney disease. PMID- 26994569 TI - Kidney keratins: cytoskeletal stress responders with biomarker potential. AB - Keratins are cytoskeletal filamentous proteins that support the structural integrity of epithelial cells. Deficiency of the major simple epithelial keratins K8, K18, and K19 increases susceptibility to hepatobiliary injury, but keratin function in kidney injury has not been addressed. Djudjaj et al. examined renal keratins in health and disease, in both mice and humans. Their findings lay the foundation for pursuing keratins as markers and regulators of renal tubular epithelial injury. PMID- 26994570 TI - Targeting the fatty acid transport protein CD36, a class B scavenger receptor, in the treatment of renal disease. AB - Augmentation of the CD36 pathway, which involves the uptake of several endogenous ligands including free fatty acids and oxidized low-density lipoprotein, contributes to the damage of proximal tubules and podocytes, whereas ablation of CD36 attenuates renal injury. Souza et al. demonstrate that 5A peptide can inhibit CD36 signaling, attenuate chronic kidney disease progression, and ameliorate inflammation and tubulointerstitial fibrosis by reducing the expression of inflammatory cytokines and chemokines, suggesting the therapeutic potential of 5A peptide against CD36-mediated renal injury. PMID- 26994571 TI - Promising biomarkers for superimposed pre-eclampsia in pregnant women with established hypertension and chronic kidney disease. AB - The incidence of pre-eclampsia is high in women with chronic kidney disease and hypertension and the diagnosis is particularly challenging. Bramham et al. (2016) studied various biomarkers with the primary aim of predicting superimposed pre eclampsia requiring delivery within 14 days of sampling. Their findings of the utility of a single biomarker for diagnosis in this high-risk group is a major advance that has significant implications and holds promise for the future. PMID- 26994572 TI - High-density lipoprotein cholesterol on a roller coaster: where will the ride end? AB - Bowe et al. report an association between low high-density lipoprotein cholesterol concentrations and various incident chronic kidney disease end points in a cohort of almost 2 million US veterans followed for 9 years. These impressive data should be a starting point for further investigations including genetic epidemiologic investigations as well as post hoc analyses of interventional trials that target high-density lipoprotein cholesterol and, finally, studies that focus on the functionality of high-density lipoprotein particles. PMID- 26994573 TI - Glomerular disease with idiopathic linear immunoglobulin deposition: a rose by any other name would be atypical. AB - Nasr et al. (2016) report 20 cases of "atypical anti-GBM disease," characterized by bright, linear glomerular basement membrane (GBM) immunoglobulin deposition in patients who lacked anti-GBM antibodies by conventional testing and who had a relatively benign course. Half had light chain restriction. The term "idiopathic linear immunoglobulin deposition" may be preferable until anti-GBM activity is demonstrable, since there are alternative mechanisms of linear deposition in the GBM, including physicochemical affinity for GBM components and alterations of the GBM itself. PMID- 26994574 TI - Recommendations for kidney disease guideline updating: a report by the KDIGO Methods Committee. AB - Updating rather than de novo guideline development now accounts for the majority of guideline activities for many guideline development organizations, including Kidney Disease: Improving Global Outcomes (KDIGO), an international kidney disease guideline development entity that has produced guidelines on kidney diseases since 2008. Increasingly, guideline developers are moving away from updating at fixed intervals in favor of more flexible approaches that use periodic expert assessment of guideline currency (with or without an updated systematic review) to determine the need for updating. Determining the need for guideline updating in an efficient, transparent, and timely manner is challenging, and updating of systematic reviews and guidelines is labor intensive. Ideally, guidelines should be updated dynamically when new evidence indicates a need for a substantive change in the guideline based on a priori criteria. This dynamic updating (sometimes referred to as a living guideline model) can be facilitated with the use of integrated electronic platforms that allow updating of specific recommendations. This report summarizes consensus based recommendations from a panel of guideline methodology professionals on how to keep KDIGO guidelines up to date. PMID- 26994576 TI - Activation of the transcription factor EB rescues lysosomal abnormalities in cystinotic kidney cells. AB - Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disease characterized by accumulation of cystine into lysosomes secondary to mutations in the cystine lysosomal transporter, cystinosin. The defect initially causes proximal tubular dysfunction (Fanconi syndrome) which in time progresses to end stage renal disease. Cystinotic patients treated with the cystine-depleting agent, cysteamine, have improved life expectancy, delayed progression to chronic renal failure, but persistence of Fanconi syndrome. Here, we have investigated the role of the transcription factor EB (TFEB), a master regulator of the autophagy-lysosomal pathway, in conditionally immortalized proximal tubular epithelial cells derived from the urine of a healthy volunteer or a cystinotic patient. Lack of cystinosin reduced TFEB expression and induced TFEB nuclear translocation. Stimulation of endogenous TFEB activity by genistein, or overexpression of exogenous TFEB lowered cystine levels within 24 hours in cystinotic cells. Overexpression of TFEB also stimulated delayed endocytic cargo processing within 24 hours. Rescue of other abnormalities of the lysosomal compartment was observed but required prolonged expression of TFEB. These abnormalities could not be corrected with cysteamine. Thus, these data show that the consequences of cystinosin deficiency are not restricted to cystine accumulation and support the role of TFEB as a therapeutic target for the treatment of lysosomal storage diseases, in particular of cystinosis. PMID- 26994575 TI - Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation. AB - Scavenger receptor CD36 participates in lipid metabolism and inflammatory pathways important for cardiovascular disease and chronic kidney disease (CKD). Few pharmacological agents are available to slow the progression of CKD. However, apolipoprotein A-I-mimetic peptide 5A antagonizes CD36 in vitro. To test the efficacy of 5A, and to test the role of CD36 during CKD, we compared wild-type to CD36 knockout mice and wild-type mice treated with 5A, in a progressive CKD model that resembles human disease. Knockout and 5A-treated wild-type mice were protected from CKD progression without changes in blood pressure and had reductions in cardiovascular risk surrogate markers that are associated with CKD. Treatment with 5A did not further protect CD36 knockout mice from CKD progression, implicating CD36 as its main site of action. In a separate model of kidney fibrosis, 5A-treated wild-type mice had less macrophage infiltration and interstitial fibrosis. Peptide 5A exerted anti-inflammatory effects in the kidney and decreased renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for CKD and its associated cardiovascular risk factors. Peptide 5A may be a promising new agent to slow CKD progression. PMID- 26994577 TI - The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. AB - Classic anti-glomerular basement membrane (GBM) disease presents with rapidly progressive glomerulonephritis (GN) with or without pulmonary hemorrhage. On biopsy typical disease displays bright polytypic linear GBM staining for IgG by immunofluorescence and diffuse crescentic/necrotizing GN on light microscopy. Here, we studied 20 patients with atypical anti-GBM nephritis typified by bright linear GBM staining for immunoglobulins but without a diffuse crescentic phenotype. Patients had hematuria, proteinuria, and mild renal insufficiency, without pulmonary hemorrhage. Light microscopy showed endocapillary proliferative GN in 9 patients, mesangial proliferative GN in 6, membranoproliferative GN in 3, and focal segmental glomerulosclerosis with mesangial hypercellularity in 2. Eight of the 20 showed features of microangiopathy. Crescents/necrosis were absent in 12 and were focal in 8 patients. Bright linear GBM staining for IgG was seen in 17 patients, IgM in 2, and IgA in 1 patient, which was polytypic in 10 patients and monotypic in 10 patients. No circulating alpha3NC1 antibodies were detected by commercial ELISA. The 1-year patient and renal survival rates were 93% and 85%, respectively. Thus, atypical anti-GBM nephritis is a rare variant of anti-GBM disease characterized clinically by an indolent course, no pulmonary involvement, and undetectable circulating alpha3NC1 antibodies. Further studies are needed to characterize the molecular architecture of GBM autoantigens in these patients and establish optimal therapy. PMID- 26994578 TI - A mind-breaking cause of acute kidney injury. PMID- 26994579 TI - Schistosoma mansoni and membranous nephropathy. PMID- 26994580 TI - The Case | The young philosopher with multiple sclerosis and proteinuria. PMID- 26994581 TI - Hyperosmolar sodium chloride is toxic to cultured neurons and causes reduction of glucose metabolism and ATP levels, an increase in glutamate uptake, and a reduction in cytosolic calcium. AB - Elevation of serum sodium, hypernatremia, which may occur during dehydration or treatment with sodium chloride, may cause brain dysfunction and damage, but toxic mechanisms are poorly understood. We found that exposure to excess NaCl, 10 100mmol/L, for 20h caused cell death in cultured cerebellar granule cells (neurons). Toxicity was due to Na(+), since substituting excess Na(+) with choline reduced cell death to control levels, whereas gluconate instead of excess Cl(-) did not. Prior to cell death from hyperosmolar NaCl, glucose consumption and lactate formation were reduced, and intracellular aspartate levels were elevated, consistent with reduced glycolysis or glucose uptake. Concomitantly, the level of ATP became reduced. Pyruvate, 10mmol/L, reduced NaCl-induced cell death. The extracellular levels of glutamate, taurine, and GABA were concentration-dependently reduced by excess NaCl; high-affinity glutamate uptake increased. High extracellular [Na(+)] caused reduction in intracellular free [Ca(2+)], but a similar effect was seen with mannitol, which was not neurotoxic. We suggest that inhibition of glucose metabolism with ensuing loss of ATP is a neurotoxic mechanism of hyperosmolar sodium, whereas increased uptake of extracellular neuroactive amino acids and reduced intracellular [Ca(2+)] may, if they occur in vivo, contribute to the cerebral dysfunction and delirium described in hypernatremia. PMID- 26994583 TI - Ultrasound visual feedback in articulation therapy following partial glossectomy. AB - Disordered speech is common following treatment for tongue cancer, however there is insufficient high quality evidence to guide clinical decision making about treatment. This study investigated use of ultrasound tongue imaging as a visual feedback tool to guide tongue placement during articulation therapy with two participants following partial glossectomy. A Phase I multiple baseline design across behaviors was used to investigate therapeutic effect of ultrasound visual feedback during speech rehabilitation. Percent consonants correct and speech intelligibility at sentence level were used to measure acquisition, generalization and maintenance of speech skills for treated and untreated related phonemes, while unrelated phonemes were tested to demonstrate experimental control. Swallowing and oromotor measures were also taken to monitor change. Sentence intelligibility was not a sensitive measure of speech change, but both participants demonstrated significant change in percent consonants correct for treated phonemes. One participant also demonstrated generalization to non-treated phonemes. Control phonemes along with swallow and oromotor measures remained stable throughout the study. This study establishes therapeutic benefit of ultrasound visual feedback in speech rehabilitation following partial glossectomy. LEARNING OUTCOMES: Readers will be able to explain why and how tongue cancer surgery impacts on articulation precision. Readers will also be able to explain the acquisition, generalization and maintenance effects in the study. PMID- 26994582 TI - In ovo treatment with an estrogen receptor alpha selective agonist causes precocious development of the female reproductive tract of the American alligator (Alligator mississippiensis). AB - The molecular signaling processes involved the differentiation of the Mullerian duct (MD) into the female reproductive tract, or oviduct, in non-mammalian vertebrates are not well understood. Studies in mammals and birds indicate that steroid hormones play a role in this process, as the embryonic MD has been shown to be vulnerable to exogenous estrogens and progestins and environmental endocrine disrupting contaminants. In a previous study, developmental treatment with an estrogen receptor alpha (ERalpha) agonist, 4,4',4"-(4-propyl-[1H] pyrazole-1,3,5-triyl)trisphenol (PPT), induced significant enlargement of the MD in alligator embryos incubated at a male-producing temperature, which was not observed in embryos treated with an estrogen receptor beta (ERbeta) agonist, 7 bromo-2-(4-hydroxyphenyl)-1,3-benzoxazol-5-ol (WAY 200070), or with 17beta estradiol (E2). In order to understand the role of estrogen signaling in female alligator oviduct development, we incubated eggs at a female-producing temperature and treated them with E2 and these ER selective agonists, PPT and WAY 200070, just prior to the thermosensitive window of sex determination. At stage 27, one stage prior to hatching, PPT induced significant enlargement of the MD with precocious development of secretory glands and connective tissue differentiation similar to characteristics of mature adult oviduct. PPT treatment in ovo increased mRNA expression of ERbeta, progesterone receptor, androgen receptor and insulin-like growth factor 1 in MD at stage 27, while expression of ERalpha was decreased. Neither WAY 200070 nor E2 treatment induced these effects seen in PPT-treated MD. The results of this study provide insight into the critical factors for healthy reproductive system formation in this sentinel species, although further investigation is needed to determine whether the observed phenomena are directly due to selective stimulation of ERalpha or related to some other aspect of PPT treatment. PMID- 26994584 TI - A QSPR study on the solvent-induced frequency shifts of acetone and dimethyl sulfoxide in organic solvents. AB - In this study, solvent-induced frequency shifts (SIFS) in the infrared spectrum of acetone and dimethyl sulfoxide in organic solvents were investigated by using four types of quantum-chemical reactivity descriptors. The results showed that the SIFS of acetone is mainly affected by the electron-acceptance chemical potential and the maximum nucleophilic condensed local softness of organic solvents, which represent the electron flow and the polarization between acetone and solvent molecules. On the other hand, the SIFS of dimethyl sulfoxide changes with the maximum positive charge of hydrogen atom and the inverse of apolar surface area of solvent molecules, showing that the electrostatic and hydrophilic interactions are main mechanisms between dimethyl sulfoxide and solvent molecules. The introduction of the four-element theory model-based quantitative structure-property relationship approach improved the assessing quality and provided a basis for interpreting the solute-solvent interactions. PMID- 26994586 TI - Exploring the virome of cattle with non-suppurative encephalitis of unknown etiology by metagenomics. AB - Non-suppurative encephalitis is one of the most frequent pathological diagnosis in cattle with neurological disease, but there is a gap in the knowledge on disease-associated pathogens. In order to identify viruses that are associated with non-suppurative encephalitis in cattle, we used a viral metagenomics approach on a sample set of 16 neurologically-diseased cows. We detected six virus candidates: parainfluenza virus 5 (PIV-5), bovine astrovirus CH13/NeuroS1 (BoAstV-CH13/NeuroS1), bovine polyomavirus 2 (BPyV-2 SF), ovine herpesvirus 2 (OvHV-2), bovine herpesvirus 6 (BHV-6) and a novel bovine betaretrovirus termed BoRV-CH15. In a case-control study using PCR, BoAstV-CH13 (p=0.046), BoPV-2 SF (p=0.005) and BoHV-6 (p=4.3E-05) were statistically associated with the disease. These data expand our knowledge on encephalitis-associated pathogens in cattle and point to the value of NGS in resolving complex infection scenarios in a clinical disease setting. PMID- 26994587 TI - Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques. AB - The outbreak of H7N9 low pathogenic avian influenza viruses in China has attracted attention to H7 influenza virus infection in humans. Since we have shown that the pathogenicity of H1N1 and H5N1 influenza viruses in macaques was almost the same as that in humans, we compared the pathogenicities of H7 avian influenza viruses in cynomolgus macaques via intranasal and conjunctival inoculation, which mimics natural infection in humans. H7N9 virus, as well as H7N7 highly pathogenic avian influenza virus, showed more efficient replication and higher pathogenicity in macaques than did H7N1 and H7N3 highly pathogenic avian influenza viruses. These results are different from pathogenicity in chickens as reported previously. Therefore, our results obtained in macaques help to estimate the pathogenicity of H7 avian influenza viruses in humans. PMID- 26994588 TI - Standardized education and parental awareness are lacking for testicular torsion. AB - INTRODUCTION: Testicular torsion leads to orchiectomy in 30-50% of cases, which may cause psychological upset and parental guilt over a potentially avertable outcome. Presentation delay is an important modifiable cause of orchiectomy; yet, families are not routinely educated about torsion or its urgency. The present study assessed parental knowledge regarding acute scrotal pain. MATERIALS AND METHODS: An anonymous survey was distributed to parents in Urology and ENT offices, asking about their children's gender and scrotal pain history, urgency of response to a child's acute scrotal pain, and familiarity with testicular torsion. RESULTS: Surveys of 479 urology and 59 ENT parents were analyzed. The results between the two were not statistically different. Among the urology parents, 34% had heard of testicular twisting/torsion, most commonly through friends, relatives or knowing someone with torsion (35%); only 17% were informed by pediatricians (Summary Figure). Parents presenting for a child's scrotal pain were significantly more likely to have heard of torsion (69%) than those presenting for other reasons (30%, OR 5.24, P < 0.0001). Only 13% of parents of boys had spoken with their children about torsion. Roughly three quarters of them would seek emergent medical attention - by day (75%) or night (82%) - for acute scrotal pain. However, urgency was no more likely among those who knew about torsion. DISCUSSION: This was the first study to assess parental knowledge of the emergent nature of acute scrotal pain in a non-urgent setting, and most closely approximating their level of knowledge at the time of pain onset. It also assessed parents' hypothetical responses to the scenario, which was markedly different than documented presentation times, highlighting a potential area for improvement in presentation times. Potential limitations included lack of respondent demographic data, potential sampling bias of a population with greater healthcare knowledge or involvement, and assessment of parents only. CONCLUSIONS: Parental knowledge of testicular torsion was lacking, suggesting both ineffective education in the well-child setting and inappropriately timed education during or after pain occurrence. Awareness was most commonly anecdotal or taught unreliably, as even familiar parents were no more likely to seek emergent attention. Therefore, standardized, effective parental education on testicular torsion and the need for prompt presentation is needed, as is improvement in the quality of information taught in the healthcare setting. Further assessment of knowledge among preadolescent and adolescent boys regarding testicular torsion is warranted. It is hopeful that pre-hospital delay may be minimized and greater rates of testicular salvageability may be achieved through these efforts. PMID- 26994589 TI - Anatomical measurements of the urogenital sinus in virilized female children due to congenital adrenal hyperplasia. AB - BACKGROUND: Virilized females due to congenital adrenal hyperplasia represent the most common form of female disorders of sexual development. The anomaly therein is an external virilization to resemble male genitalia and a persistent urogenital sinus. OBJECTIVES: To study the anatomical details of the virilized female cases operated upon between 2011 and 2015. This anatomical description is presented to support the current surgical strategy of partial urogenital mobilization to correct this anomaly. METHODS: Thirty cases (presenting to a single tertiary center) were prospectively studied by genitography, cysto urethroscopy, and operated upon via a single-stage feminizing genitoplasty. A single surgical team operated upon all cases. External virilization was assessed by the Prader classification. The internal anatomy was studied by measuring the length of the urethra proximal to the confluence, and the vertical depth of the vaginal-urethral confluence from the perineum. The correlation coefficients between the external virilization and the internal anatomical measurements were derived. RESULTS: The median age at surgery was 19 months (range 6-42 months). External virilization did not obviously correlate with the length of the proximal (prejunctional) urethra (r = -0.03, P = 0.5), or strongly with the depth of the vaginal-urethral confluence (r = 0.2, P = 0.2). The mean length of the proximal urethra was 22 mm (range 10-32 mm), and the mean vertical depth of the vaginal urethral confluence from the perineum was 16 mm (range 8-31 mm). DISCUSSION: Due to limitations of the radiological and endoscopic evaluation, the accurate anatomical assessment of this condition may be challenging. In order to assess or compare the anatomy of these cases, there are two important points to address: (1) the length of the urethra proximal to the urogenital sinus, as this will impact the urinary outcome; and (2) the depth (level) of vaginal entry into the urogenital sinus, as this will affect the mobilization required to exteriorize the vagina. CONCLUSION: The degree of external virilization does not totally correlate with the internal anatomy. The depth of the vaginal-urethral confluence from the perineum is an indicator of the required mobilization for the current perineal approach. In 90% of cases in this age group (1-3 years old), this depth is <=20 mm. This supports the current understanding that partial urogenital mobilization could be suitable for most cases Figure (Summary). PMID- 26994590 TI - Color-Coded Super-Resolution Small-Molecule Imaging. AB - Although the development of super-resolution microscopy dates back to 1994, its applications have been primarily focused on visualizing cellular structures and targets, including proteins, DNA and sugars. We now report on a system that allows both monitoring of the localization of exogenous small molecules in live cells at low resolution and subsequent super-resolution imaging by using stochastic optical reconstruction microscopy (STORM) on fixed cells. This represents a powerful new tool to understand the dynamics of subcellular trafficking associated with the mode and mechanism of action of exogenous small molecules. PMID- 26994591 TI - Bioengineered protein-based nanocage for drug delivery. AB - Nature, in its wonders, presents and assembles the most intricate and delicate protein structures and this remarkable phenomenon occurs in all kingdom and phyla of life. Of these proteins, cage-like multimeric proteins provide spatial control to biological processes and also compartmentalizes compounds that may be toxic or unstable and avoids their contact with the environment. Protein-based nanocages are of particular interest because of their potential applicability as drug delivery carriers and their perfect and complex symmetry and ideal physical properties, which have stimulated researchers to engineer, modify or mimic these qualities. This article reviews various existing types of protein-based nanocages that are used for therapeutic purposes, and outlines their drug-loading mechanisms and bioengineering strategies via genetic and chemical functionalization. Through a critical evaluation of recent advances in protein nanocage-based drug delivery in vitro and in vivo, an outlook for de novo and in silico nanocage design, and also protein-based nanocage preclinical and future clinical applications will be presented. PMID- 26994593 TI - Deficits in voice and multisensory processing in patients with Prader-Willi syndrome. AB - Prader-Willi syndrome (PWS) is a rare neurodevelopmental and genetic disorder that is characterized by various expression of endocrine, cognitive and behavioral problems, among which a true obsession for food and a deficit of satiety that leads to hyperphagia and severe obesity. Neuropsychological studies have reported that PWS display altered social interactions with a specific weakness in interpreting social information and in responding to them, a symptom closed to that observed in autism spectrum disorders (ASD). Based on the hypothesis that atypical multisensory integration such as face and voice interactions would contribute in PWS to social impairment we investigate the abilities of PWS to process communication signals including the human voice. Patients with PWS recruited from the national reference center for PWS performed a simple detection task of stimuli presented in an uni-o or bimodal condition, as well as a voice discrimination task. Compared to control typically developing (TD) individuals, PWS present a specific deficit in discriminating human voices from environmental sounds. Further, PWS present a much lower multisensory benefits with an absence of violation of the race model indicating that multisensory information do not converge and interact prior to the initiation of the behavioral response. All the deficits observed in PWS were stronger for the subgroup of patients suffering from Uniparental Disomy, a population known to be more sensitive to ASD. Altogether, our study suggests that the deficits in social behavior observed in PWS derive at least partly from an impairment in deciphering the social information carried by voice signals, face signals, and the combination of both. In addition, our work is in agreement with the brain imaging studies revealing an alteration in PWS of the "social brain network" including the STS region involved in processing human voices. PMID- 26994594 TI - Early memories in social anxiety: A meaningful and enduring collaboration with my Dad. AB - In this short paper in honour of my father's Festschrift, I describe a recent collaboration with him in which we joined forces to investigate the nature of autobiographical images and memories in social anxiety. I outline our work together and the unique insights that were gleaned from our interactive contributions. Then, I reflect on how this collaboration has helped to lay the foundation for subsequent work in my lab and illuminate new directions in my program of research, enhance my career as a scientist-practitioner, and ultimately, enrich both my personal and professional identities. In so doing, I aim to highlight one of the most important and enduring aspects of my father's legacy: the profound positive impact he has on the people with whom he has worked. PMID- 26994595 TI - Fine-needle aspiration diagnosis of primary hydatid disease of the thyroid; first reported case in the USA. AB - Echinococcosis or hydatid disease (HD) is a parasitic disease caused by species of the Echinococcus genus. Since the incidence of HD in the USA is very low and the primary HD of the thyroid is extremely rare even in endemic regions, the occurrence of primary thyroid HD is exceptional in the USA. Thyroid HD is rarely diagnosed by fine-needle aspiration (FNA). Our literature review revealed less than ten cases of primary HD of thyroid diagnosed by FNA worldwide. Hereby, we report the first case of a primary thyroid HD diagnosed by fine-needle aspiration in the USA. PMID- 26994592 TI - Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos. AB - The main goal of drug delivery systems is to target therapeutic cargoes to desired cells and to ensure their efficient uptake. Recently a number of studies have focused on designing bio-inspired nanocarriers, such as bacteriophages, and synthetic carriers based on the bacteriophage structure. Bacteriophages are viruses that specifically recognize their bacterial hosts. They can replicate only inside their host cell and can act as natural gene carriers. Each type of phage has a particular shape, a different capacity for loading cargo, a specific production time, and their own mechanisms of supramolecular assembly, that have enabled them to act as tunable carriers. New phage-based technologies have led to the construction of different peptide libraries, and recognition abilities provided by novel targeting ligands. Phage hybridization with non-organic compounds introduces new properties to phages and could be a suitable strategy for construction of bio-inorganic carriers. In this review we try to cover the major phage species that have been used in drug and gene delivery systems, and the biological application of phages as novel targeting ligands and targeted therapeutics. PMID- 26994596 TI - Comparison of the Osteogenic Potential of Mineral Trioxide Aggregate and Endosequence Root Repair Material in a 3-dimensional Culture System. AB - INTRODUCTION: The ability to promote osteoblast differentiation is a desirable property of root-end filling materials. Several in vitro studies compare the cytotoxicity and physical properties between mineral trioxide aggregate (MTA) and Endosequence root repair material (ERRM), but not their osteogenic potential. Three-dimensional cultures allow cells to better maintain their physiological morphology and better resemble in vivo cellular response than 2-dimensional cultures. Here we examined the osteogenic potential of MTA and ERRM by using a commercially available 3-dimensional Alvetex scaffold. METHODS: Mandibular osteoblasts were derived from 3-week-old male transgenic reporter mice where mature osteoblasts express green fluorescent protein (GFP) driven by a 2.3 kilobase type I collagen promoter (Col(I)-2.3). Mandibular osteoblasts were grown on Alvetex in direct contact with MTA, ERRM, or no material (negative control) for 14 days. Osteoblast differentiation was evaluated by expression levels of osteogenic genes by using quantitative polymerase chain reaction and by the spatial dynamics of Col(I)-2.3 GFP-positive mature osteoblasts within the Alvetex scaffolds by using 2-photon microscopy. RESULTS: ERRM significantly increased alkaline phosphatase (Alp) and bone sialoprotein (Bsp) expression compared with MTA and negative control groups. Both MTA and ERRM increased osterix (Osx) mRNA significantly compared with the negative control group. The percentage of Col(I) 2.3 GFP-positive cells over total cells within Alvetex was the highest in the ERRM group, followed by MTA and by negative controls. CONCLUSIONS: ERRM promotes osteoblast differentiation better than MTA and controls with no material in a 3 dimensional culture system. Alvetex scaffolds can be used to test endodontic materials. PMID- 26994597 TI - Apical Closure in Apexification: A Review and Case Report of Apexification Treatment of an Immature Permanent Tooth with Biodentine. AB - Materials such as calcium hydroxide paste and mineral trioxide aggregate are used in apexification treatment of immature permanent teeth, but the search for improved materials with higher characteristics of biocompatibility results in different materials. Biodentine is a tricalcium silicate cement that possesses adequate handling characteristics and acceptable mechanical and bioactivity properties. This report describes the case of a 9-year-old boy who was referred to the Department of Dental Clinic of Queretaro Autonomous University of Mexico. One month prior the patient had suffered a dental trauma of his upper left central incisor and had been treated by another dentist. The clinical diagnosis was previously initiated therapy and symptomatic apical periodontitis. The treatment was apexification with Biodentine. At follow-ups performed at 3, 6, and 18 months after treatment the tooth was asymptomatic. The cone-beam computed tomography scan at 18-month postoperative follow-up revealed continuity of periodontal ligament space, absence of periapical rarefactions, and a thin layer of calcified tissue formed apical to the Biodentine barrier. On the basis of sealing ability and biocompatibility, apexification treatment with Biodentine was applied in the present case report. The favorable clinical and radiographic outcome in this case demonstrated that Biodentine may be an efficient alternative to the conventional apexification materials. PMID- 26994598 TI - Analysis of the Root and Canal Morphologies in Maxillary First and Second Molars in a Chinese Population Using Cone-beam Computed Tomography. AB - INTRODUCTION: We analyzed and characterized the root and canal morphologies in maxillary first and second molars in a large sample of Chinese patients using reconstructed cone-beam computed tomographic (CBCT) imaging. METHODS: Maxillary first (n = 1558) and second (n = 1539) molars were collected from Chinese patients (N = 844) who had undergone in vivo CBCT imaging. The root canal number and morphology were determined according to Vertucci's classification. RESULTS: A single root was found in 0.06% of first molars, which showed type I canal systems. However, second molars with a single root (4.2%) showed widely varied canal systems. The buccal roots of first molars with 2 separate roots showed type I, II, or III canal systems, whereas those of 2-rooted second molars showed widely varied canal systems. The incidence of fused roots was 1.38% for first molars and 23.9% for second molars, whereas canal fusion within fused roots was observed in 4.5% of first molars and 10.6% of second molars. Additional canals were observed in 67.8% and 29.7% of mesiobuccal roots, 1.8% and 0.7% of distobuccal roots, and 0.7% and 0.3% of palatal roots in 1523 and 1017 first and second molars with 3 separate roots, respectively. The mesiobuccal root canal number showed bilateral symmetry between 79% of first molars and 82.3% of second molars, with a concurrence rate of 59.8% between adjacent molars. CONCLUSIONS: We reported the root and canal morphologic variations in maxillary first and second molars, which have not been reported for Chinese populations. Further studies should focus on canals in fused roots and mesiobuccal roots. PMID- 26994599 TI - Synchrotron-based Phase Contrast-enhanced Micro-Computed Tomography Reveals Delaminations and Material Tearing in Water-expandable Root Fillings Ex Vivo. AB - INTRODUCTION: This study evaluated the integrity of calcium silicate sealer-based fillings made with hygro-expandable cones (HEC) that are commercially known as CPoint or Smartpoint. METHODS: Fourteen human canines were prepared according to a standardized, conventional endodontic treatment protocol and filled with the HEC/calcium silicate sealer. Three-dimensional imaging was performed with laboratory micro-computed tomography (MUCT) at its highest resolution and was compared with synchrotron phase contrast-enhanced MUCT (PCE-CT) scans of the treatment extending 1-7 mm from the apex. Conventional destructive optical microscopy validated observations by comparison with virtual slices in the tomographic data. RESULTS: Conventional laboratory MUCT at 10-MUm resolution did not reveal the existing voids and defects within the root canal fillings. PCE-CT revealed elongated interfacial delamination localized mainly at the HEC-sealer interface forming extended through-and-through gaps along the root canal filling. CONCLUSIONS: Endodontic studies that use conventional laboratory MUCT may underestimate thin defects and delamination within root canal fillings made with HEC because of limited resolution and contrast of laboratory-based broad-spectrum low intensity x-ray sources. These limitations favor use of high-brilliance, monochromatic synchrotron-based PCE-CT to reveal the important micrometer details within large (millimeter sized) samples. PCE-CT revealed the existence of a range of significant structural defects in recently placed HEC fillings, confirmed by optical microscopy after physical sectioning. Substantial delamination spanning 20%-40% of the circumferential interface as well as other structural defects were identified within root canal fillings made of HEC and calcium silicate sealer. PMID- 26994600 TI - Spectroscopic characterization of dissolved organic matter derived from different biochars and their polycylic aromatic hydrocarbons (PAHs) binding affinity. AB - In recent years, biochar has received a great attention due to its high application in different sectors of environment. The feasibility of biochar applications is depended on its physical and chemical properties and biochar derived dissolved organic matter (DOM) characteristics. This study was conducted to investigate the spectroscopic characteristics of biochar-derived DOM and its binding capacity of hydrophobic organic chemicals (HOCs). DOM solutions were isolated from five different biochars prepared through pyrolysis and analyzed for dissolved organic carbon (DOC) contents. The optical analysis with UV-visible absorption and excitation-emission matrix (EEM) fluorescence spectroscopes and DOC water distribution coefficient (KDOC) were calculated in the presence of PAHs and DOM. The DOC contents and the estimated aromaticity (SUVA254) were different for selected biochars. The DOM derived from soybean straw biochar (SBBC) showed the highest DOC contents followed by rice straw biochar (RSBC). The SBBC and RSBC peak position in the fluorescence excitation/emission matrix at longer wavelength corresponded to the peak position of other three biochars indicating that SBBC and RSBC had relatively higher degree of humification. This was well correlated with the observed KDOC values, suggesting that the KDOC value(')s dominant factor was the degree of biochar-derived DOM humification. The results of this study indicate that the optical analysis may provide valuable information regarding the characteristics of biochar-derived DOM and its application as environmental amendments for minimization of toxic organic compounds. PMID- 26994601 TI - Defining the wheat gluten peptide fingerprint via a discovery and targeted proteomics approach. AB - Accurate, reliable and sensitive detection methods for gluten are required to support current EU regulations. The enforcement of legislative levels requires that measurement results are comparable over time and between methods. This is not a trivial task for gluten which comprises a large number of protein targets. This paper describes a strategy for defining a set of specific analytical targets for wheat gluten. A comprehensive proteomic approach was applied by fractionating wheat gluten using RP-HPLC (reversed phase high performance liquid chromatography) followed by a multi-enzymatic digestion (LysC, trypsin and chymotrypsin) with subsequent mass spectrometric analysis. This approach identified 434 peptide sequences from gluten. Peptides were grouped based on two criteria: unique to a single gluten protein sequence; contained known immunogenic and toxic sequences in the context of coeliac disease. An LC-MS/MS method based on selected reaction monitoring (SRM) was developed on a triple quadrupole mass spectrometer for the specific detection of the target peptides. The SRM based screening approach was applied to gluten containing cereals (wheat, rye, barley and oats) and non-gluten containing flours (corn, soy and rice). A unique set of wheat gluten marker peptides were identified and are proposed as wheat specific markers. SIGNIFICANCE: The measurement of gluten in processed food products in support of regulatory limits is performed routinely. Mass spectrometry is emerging as a viable alternative to ELISA based methods. Here we outline a set of peptide markers that are representative of gluten and consider the end user's needs in protecting those with coeliac disease. The approach taken has been applied to wheat but can be easily extended to include other species potentially enabling the MS quantification of different gluten containing species from the identified markers. PMID- 26994603 TI - Subacromial shoulder disorders among baggage handlers: an observational cohort study. AB - PURPOSE: To assess the influence of cumulative employment as baggage handler on the risk of incident subacromial shoulder disorders. Baggage handling is characterized by repetitive work primarily consisting of heavy lifting in awkward positions and time pressure. METHODS: This cohort study is based on the Copenhagen Airport Cohort consisting of unskilled men with employment at Copenhagen Airport and unskilled men with employment in other firms in the Greater Copenhagen area during the period 1990-2012. Only men were included. We followed the cohort in the National Patient Register and Civil Registration System. The primary exposure was cumulative years of employment as a baggage handler, and the primary outcome was diagnoses and surgical treatment of subacromial shoulder disorders. RESULTS: The cohort contained 3396 baggage handlers and 63,909 workers in the reference group. Baggage handlers with longer cumulative years of employment had higher incidence compared to baggage handlers with shorter employment; for example, baggage handlers with 10-19 years of employment had incidence rate ratio of 2.07 (95 % confidence interval, 1.27-3.38) compared to baggage handlers with less than 3 years of employment. Spline regression showed an increase in incidence within the first few years after employment whereupon the increased risk remained constant for longer employment. Baggage handlers had increased incidence in younger ages than the reference population. CONCLUSIONS: In this large cohort study, we found increased incidence of subacromial shoulder disorders for workers with longer cumulative years of employment. These results support that long-term lifting in awkward positions and time pressure influences the risk of subacromial shoulder disorders. PMID- 26994602 TI - Pharmacokinetics of Oral and Intravenous Oseltamivir Treatment of Severe Influenza B Virus Infection Requiring Organ Replacement Therapy. AB - BACKGROUND AND OBJECTIVES: Patients with severe influenza virus infection, multi organ failure and organ replacement therapy may absorb and metabolize neuraminidase inhibitors differently. Systematic pharmacokinetic/pharmacodynamic clinical trials are currently lacking in this high-risk group. Inadequate dosing increases the risk of treatment failure and drug resistance, especially in severely ill patients with elevated virus loads. This study aims to explore the impact of organ replacement therapy on oseltamivir drug concentrations. METHODS: Serial pharmacokinetic/pharmacodynamic measurements and Sieving coefficients were assessed in two patients with severe influenza B infection requiring organ replacement therapy. RESULTS: Patient #1, a 9-year-old female with severe influenza B virus infection, biventricular assist device, and continuous veno venous hemodiafiltration, received 75 mg oral oseltamivir twice-daily for 2 days, then intravenous oseltamivir with one-time renoprotective dosing (40 mg), followed by regular intravenous administration of 100 mg twice-daily. Plasma oseltamivir carboxylate concentrations were stable initially, but only regular administration of 100 mg resulted in virus load decline and clinical improvement. Patient #2, a 28-year-old female with influenza B virus infection requiring extracorporeal membrane oxygenation, received 75 mg oral oseltamivir twice-daily, resulting in erratic oseltamivir blood concentrations. In both patients, drug concentrations remained well within safety margins. CONCLUSIONS: In severe cases with multi-organ failure, administration of 100 mg intravenous oseltamivir twice daily provided reliable drug concentrations, as opposed to renoprotective and oral dosing, thereby minimizing the risk of treatment failure and drug resistance. Evidence-based pediatric dosing recommendations and effective intravenous antiviral treatment modalities are needed for intensive care patients with life-threatening influenza disease. PMID- 26994604 TI - Irrigation and Maize Cultivation Erode Plant Diversity Within Crops in Mediterranean Dry Cereal Agro-Ecosystems. AB - The intensification of agriculture has increased production at the cost of environment and biodiversity worldwide. To increase crop yield in dry cereal systems, vast farmland areas of high conservation value are being converted into irrigation, especially in Mediterranean countries. We analyze the effect of irrigation-driven changes on the farm biota by comparing species diversity, community composition, and species traits of arable plants within crop fields from two contrasting farming systems (dry and irrigated) in Spain. We sampled plant species within 80 fields of dry wheat, irrigated wheat, and maize (only cultivated under irrigation). Wheat crops held higher landscape and per field species richness, and beta diversity than maize. Within the same type of crop, irrigated wheat hosted lower plant diversity than dry wheat at both field and landscape scales. Floristic composition differed between crop types, with higher frequencies of perennials, cosmopolitan, exotic, wind-pollinated and C4 species in maize. Our results suggest that irrigation projects, that transform large areas of dry cereal agro-ecosystems into irrigated crop systems dominated by maize, erode plant diversity. An adequate planning on the type and proportion of crops used in the irrigated agro-ecosystems is needed in order to balance agriculture production and biodiversity conservation. PMID- 26994606 TI - Geographic Distribution of Healthy Resources and Adverse Pregnancy Outcomes. AB - Objective To determine the risk of gestational diabetes (GDM) and preeclampsia associated with various community resources. Methods An ecological study was performed in Los Angeles and Orange counties in California. Fast food restaurants, supermarkets, grocery stores, gyms, health clubs and green space were identified using Google (c) Maps Extractor and through the Southern California Association of Government. California Birth Certificate data was used to identify cases of GDM and preeclampsia. Unadjusted and adjusted risk ratios were calculated using negative binomial regression. Results There were 9692 cases of GDM and 6288 cases of preeclampsia corresponding to incidences of 2.5 and 1.4 % respectively. The adjusted risk of GDM was reduced in zip codes with greater concentration of grocery stores [relative risk (RR) 0.95, 95 % confidence interval (CI) 0.92-0.99] and supermarkets (RR 0.94, 95 % CI 0.90-0.98). There were no significant relationships between preeclampsia and the concentration of fast food restaurants, grocery store, supermarkets or the amount of green space. Conclusion The distribution of community resources has a significant association with the risk of developing GDM but not preeclampsia. PMID- 26994605 TI - Influence of fat intake and BMI on the association of rs1799983 NOS3 polymorphism with blood pressure levels in an Iberian population. AB - PURPOSE: There is controversy about the effect of the rs1799983 nitric oxide synthase (NOS3) genetic variant on hypertension and blood pressure (BP) levels. The aims of the current study were to examine whether rs1799983 affects BP levels and to identify potential interactions between this polymorphism and other non genetic risk factors. METHODS: A total of 705 subjects were examined for anthropometric and body composition measurements, BP, dietary habits and physical activity. Oral epithelial cells were collected for the identification of rs1799983 using Luminex(r) 100/200TM System. RESULTS: After adjusted for covariates, TT genotype showed a 2.30-fold higher predisposition of hypertension than GG genotype subjects. According to BP levels, for each risk allele diastolic blood pressure (DBP) increased in 1.99 mmHg. Significant interactions between rs1799983 and saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) were found. Moreover, an interaction with body weight status was observed. Among overweight individuals, T allele carriers showed higher DBP than GG genotype. CONCLUSION: The present study evidenced that rs1799983 NOS3 polymorphism could be associated with hypertension and DBP among Southern Europeans, being this association influenced by dietary fat (SFA and MUFA) and body mass index. PMID- 26994607 TI - WIC Participation and Breastfeeding at 3 Months Postpartum. AB - Objectives Participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has been associated with lower breastfeeding initiation and duration. This study examines breastfeeding-related factors among WIC participants and nonparticipants that might explain these previous findings. Methods Respondents to the 2007 Infant Feeding Practices Study II who were income eligible for WIC were categorized as follows: no WIC participation (No-WIC); prenatal participation and infant entry while >=60 % breastfeeding (WIC BF-high); prenatal participation and infant entry while <60 % breastfeeding (WIC BF-low). Percent breastfeeding was the number of breast milk feeds divided by the total number of liquid feeds. Using propensity scores, we matched WIC BF-high respondents to No-WIC respondents on demographic and breastfeeding factors. We used logistic regression to estimate the impact of WIC participation on breastfeeding at 3 months postpartum in the matched sample. Within-WIC differences were explored. Results Of 743 income-eligible respondents, 293 never enrolled in WIC, 230 were categorized as WIC BF-high, and 220 as WIC BF-low. Compared to matched No-WIC respondents, WIC BF-high respondents had increased odds of breastfeeding at 3 months, though this difference was not statistically significant (OR 1.92; 95 % CI 0.95-3.67; p value 0.07). WIC BF-high respondents were more similar on breastfeeding-related characteristics to No-WIC respondents than to WIC BF-low respondents. Conclusions for Practice Accounting for prenatal breastfeeding intentions and attitudes, we find no negative association between WIC participation and breastfeeding at 3 months postpartum. This is in contrast to prior studies, and highlights the importance of understanding within-WIC differences. PMID- 26994608 TI - Prenatal and Postnatal Fruit and Vegetable Intake Among US Women: Associations with WIC Participation. AB - Objective Evaluate variation in fruit and vegetable intake by Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) participation and poverty status among pregnant, and postpartum women participating in the Infant Feeding Practice Study II (IFPSII). Methods IFPSII (2005-2007) followed US women from third trimester through 1 year postpartum through mailed questionnaires measuring income, WIC participation, breastfeeding; and dietary history questionnaires (DHQ) assessing prenatal/postnatal fruit and vegetable consumption. Poverty measurements used U.S. Census Bureau Federal Poverty thresholds to calculate percent of poverty index ratio (PIR) corresponding to WIC's financial eligibility (<=185 % PIR). Comparison groups: WIC recipients; WIC eligible (<=185 % PIR), but non-recipients; and women not financially WIC eligible (>185 % PIR). IFPSII participants who completed at least one DHQ were included. Intake variation among WIC/poverty groups was assessed by Kruskal-Wallis tests and between groups by Mann-Whitney Wilcoxon tests and logistic regression. Mann-Whitney Wilcoxon tests examined postnatal intake by breastfeeding. Results Prenatal vegetable intake significantly varied by WIC/poverty groups (p = 0.04) with WIC recipients reporting significantly higher intake than women not financially WIC eligible (p = 0.02); association remained significant adjusting for confounders [odds ratio 0.66 (95 % confidence interval: 0.49-0.90)]. Prenatal fruit and postnatal consumption did not significantly differ by WIC/poverty groups. Postnatal intake was significantly higher among breastfeeding than non-breastfeeding women (fruit: p < 0.0001; vegetable: p = 0.006). Conclusions for Practice Most intakes did not significantly differ by WIC/poverty groups and thus prompts research on WIC recipient's dietary behaviors, reasons for non-participation in WIC, and the influence of the recent changes to the WIC food package. PMID- 26994609 TI - A Survey of Obstetric Healthcare Utilization in the Rural Western Indian Himalayas. AB - Objectives To determine the socio-economic factors affecting access to antepartum, intrapartum, and postpartum healthcare in the rural Western Indian Himalayas over the past 20 years. Methods Face-to-face surveys were conducted with 197 women in Chamoli District, Uttarakhand from October 2011 to May 2012. Participants who gave birth within the past 20 years were included in the final analysis (n = 158). Stratified odds ratios and analysis of variance were calculated. Results Among women who delivered in the prior 7 years, there was a nine-fold increase (95 % CI 4-20.8) in institutionalized births compared to women who delivered 8-20 years before the study. Among women who delivered 7 years prior to the study, low income increased the risk of home delivery (OR 3.07, 95 % CI 1.15-8.54). Low caste (OR 2.79, 95 % CI 1.04-7.72) and low level of education (OR 3.93 95 % CI 1.41-11.81) decreased the use of antepartum medications (vitamins and vaccines). Remote location among all participants was a risk factor for not seeking care for obstetric morbidities (OR 0.44 95 % CI 0.2-0.95). Conclusions The incidence of institutionalized delivery has increased over the past decade in rural Uttarakhand. Income, caste, education, and remote location correlated with poor access to antepartum and intrapartum healthcare. These correlations have increased in statistical significance over the past 20 years, except for location. This indicates that the Western Himalayas face similar challenges to obstetric service utilization as the north Indian plains and that several of these inequalities in healthcare access have become more pronounced in recent years. PMID- 26994610 TI - The Effects of Chewing Betel Nut with Tobacco and Pre-pregnancy Obesity on Adverse Birth Outcomes Among Palauan Women. AB - The small Pacific Island nation of Palau has alarmingly high rates of betel nut with tobacco use and obesity among the entire population including pregnant women. This study aimed to determine the effects of betel nut with tobacco use and pre-pregnancy obesity on adverse birth outcomes. This study used retrospective cohort data on 1171 Palauan women who gave birth in Belau National Hospital in Meyuns, Republic of Palau between 2007 and 2013. The exposures of interest were pre-pregnancy obesity and reported betel nut with tobacco use during pregnancy. The primary outcomes measured were preterm birth and low birth weight among full-term infants. A significantly increased risk for low birth weight among full-term infants was demonstrated among those women who chewed betel nut with tobacco during pregnancy when other known risk factors were controlled for. Additionally, pre-pregnancy obesity was associated with a significantly increased risk for preterm birth when other known risk factors were controlled for. Both betel nut with tobacco use and pre-pregnancy obesity were associated with higher risks for adverse birth outcomes. These findings should be used to drive public health efforts in Palau, as well as in other Pacific Island nations where these studies are currently lacking. PMID- 26994611 TI - Pheromonal Cues Deposited by Mated Females Convey Social Information about Egg Laying Sites in Drosophila Melanogaster. AB - Individuals can make choices based on information learned from others, a phenomenon called social learning. How observers differentiate between which individual they should or should not learn from is, however, poorly understood. Here, we showed that Drosophila melanogaster females can influence the choice of egg-laying site of other females through pheromonal marking. Mated females mark territories of high quality food by ejecting surplus male sperm containing the aggregation pheromone cis-11-vaccenyl acetate (cVA) and, in addition, deposit several sex- and species-specific cuticular hydrocarbon (CHC) pheromones. These pheromonal cues affect the choices of other females, which respond by preferentially laying eggs on the marked food. This system benefits both senders and responders, as communal egg laying increases offspring survival. Virgin females, however, do not elicit a change in the egg-laying decision of mated females, even when food has been supplemented with ejected sperm from mated females, thus indicating the necessity for additional cues. Genetic ablation of either a female's CHC pheromones or those of their mate results in loss of ability of mated females to attract other females. We conclude that mated females use a pheromonal marking system, comprising cVA acquired from male ejaculate with sex- and species-specific CHCs produced by both mates, to indicate egg-laying sites. This system ensures information reliability because mated, but not virgin, females have both the ability to generate the pheromone blend that attracts other flies to those sites and a direct interest in egg-laying site quality. PMID- 26994612 TI - The Presence Of Strange Males' Odor Induces Behavioral Responses And Elevated Levels Of Low Molecular Weight Proteins Excreted In The Urine Of Mature Water Vole Males (Arvicola amphibius L). AB - We hypothesized that low molecular weight urinary proteins play a role in male male chemical communication in the water vole, Arvicola ampibius L. We studied the effect of placing soiled litter from strange males into the cage of another sexually mature male on the intensity of its digging and scattering, urination on the litter, and alteration in the levels of low molecular weight proteins (15-25 kDa) excreted in the urine before and after 4 days of exposure as determined by chip electrophoresis. The intensity of digging and scattering was positively correlated with levels of testosterone in serum of males exposed to strange male odors (r = 0.56; P < 0.01), as well as with the concentration of low molecular weight proteins in the donor's urine (r = 0.52, P < 0.05). At the end of the experiment, the level of low molecular weight protein in excreted urine was elevated in the males exposed to the strange male's litter. These results highlight the importance of quantitative inter-individual variation of low molecular weight urinary proteins in the modulation of the physiology and behavior of conspecifics. PMID- 26994613 TI - Varying butyric acid amounts induce different stress- and cell death-related signals in nerve growth factor-treated PC12 cells: implications in neuropathic pain absence during periodontal disease progression. AB - Neuropathic pain is absent from the early stages of periodontal disease possibly due to neurite retraction. Butyric acid (BA) is a periodontopathic metabolite that activates several stress-related signals and, likewise, induce neurite retraction. Neuronal cell death is associated to neurite retraction which would suggest that BA-induced neurite retraction is ascribable to neuronal cell death. However, the underlying mechanism of BA-related cell death signaling remains unknown. In this study, we exposed NGF-treated PC12 cells to varying BA concentrations [0 (control), 0.5, 1.0, 5.0 mM] and determined selected stress related (H2O2, glutathione reductase, calcium (Ca(2+)), plasma membrane Ca(2+) ATPase (PMCA), and GADD153/CHOPS) and cell death-associated (extrinsic: FasL, TNF alpha, TWEAK, and TRAIL; intrinsic: cytochrome C (CytC), NF-kB, CASP8, CASP9, CASP10, and CASP3) signals. Similarly, we confirmed cell death execution by chromatin condensation. Our results showed that low (0.5 mM) and high (1.0 and 5.0 mM) BA levels differ in stress and cell death signaling. Moreover, at periodontal disease-level BA concentration (5 mM), we observed that only FasL amounts were affected and occurred concurrently with chromatin condensation insinuating that cells have fully committed to neurodegeneration. Thus, we believe that both stress and cell death signaling in NGF-treated PC12 cells are affected differently depending on BA concentration. In a periodontal disease scenario, we hypothesize that during the early stages, low BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurite non proliferation, whereas, during the later stages, high BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurodegeneration. More importantly, we propose that neuropathic pain absence at any stage of periodontal disease progression is ascribable to BA accumulation regardless of amount. PMID- 26994614 TI - Tensor factorization toward precision medicine. AB - Precision medicine initiatives come amid the rapid growth in quantity and variety of biomedical data, which exceeds the capacity of matrix-oriented data representations and many current analysis algorithms. Tensor factorizations extend the matrix view to multiple modalities and support dimensionality reduction methods that identify latent groups of data for meaningful summarization of both features and instances. In this opinion article, we analyze the modest literature on applying tensor factorization to various biomedical fields including genotyping and phenotyping. Based on the cited work including work of our own, we suggest that tensor applications could serve as an effective tool to enable frequent updating of medical knowledge based on the continually growing scientific and clinical evidence. We encourage extensive experimental studies to tackle challenges including design choice of factorizations, integrating temporality and algorithm scalability. PMID- 26994615 TI - Hemodynamically Significant Congenital Cardiac Lesions in Pregnancy. AB - OPINION STATEMENT: The incidence of congenital cardiac disease among reproductive aged women is increasing. Understanding the unique physiology of pregnancy and the postpartum period is critical to helping women achieve successful pregnancy outcomes. Risk assessment models estimate the cardiac, obstetric, and neonatal risks a woman may face and influence the conversations regarding pregnancy and contraception management. This review focuses on some of the most common congenital cardiac lesion encountered during pregnancy, as well as key aspects of antepartum, intrapartum, and postpartum care for these women. A multidisciplinary team, with Maternal-Fetal Medicine, Cardiology and Obstetric Anesthesiology specialists, is critical to the care of these patients. PMID- 26994616 TI - Effects of prolonged fasting on fatigue and quality of life in patients with multiple sclerosis. AB - Fasting is one of the recommended worships of several great religions in the world. During the month of Ramadan, circadian rhythm and pattern of eating changes result in physiological, biochemical and hormonal changes in the body. Many Muslims with medical conditions ask their physicians about the feasibility and safety of fasting during Ramadan. In this study, we aim to assess the effect of Ramadan fasting on the quality of life and fatigue in multiple sclerosis (MS) patients. Relapsing-remitting MS (RRMS) patients according to McDonald's criteria who had mild disability (EDSS score <=3) were included in this study. Fatigue and quality of life were were assessed using the validated Persian versions of modified fatigue impact scale (MFIS) and multiple sclerosis quality of life-54 (MSQOL-54) questionnaires, respectively. 218 patients (150 females and 68 males) were enrolled in our study. There was no statistically significant difference between the mean total score of MSIF before and after fasting (25.50 +/- 13.81 versus 26.94 +/- 16.65; p = 0.58). The mean physical health and mental health composites of quality of life increased significantly after fasting (p = 0.008 and p = 0.003 respectively). Despite the observed lack of favorable effects on fatigue, our results showed increased quality of life of MS patients once Ramadan has ended. Whether this is specifically related to Ramadan-related fasting deserves further testing in appropriately designed larger prospective clinical studies. PMID- 26994617 TI - The kinesin Eg5 inhibitor K858 induces apoptosis but also survivin-related chemoresistance in breast cancer cells. AB - Inhibitors of kinesin spindle protein Eg5 are characterized by pronounced antitumor activity. Our group has recently synthesized and screened a library of 1,3,4-thiadiazoline analogues with the pharmacophoric structure of K858, an Eg5 inhibitor. We herein report the effects of K858 on four different breast cancer cell lines: MCF7 (luminal A), BT474 (luminal B), SKBR3 (HER2 like) and MDA-MB231 (basal like). We demonstrated that K858 displayed anti-proliferative activity on every analyzed breast cancer cell line by inducing apoptosis. However, at the same time, we showed that K858 up-regulated survivin, an anti-apoptotic molecule. We then performed a negative regulation of survivin expression, with the utilization of wortmannin, an AKT inhibitor, and obtained a significant increase of K858-dependent apoptosis. These data demonstrate that K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis. PMID- 26994618 TI - Mercury Enrichment in Sediments of the Coastal Area of Northern Latium, Italy. AB - The purpose of this study was to evaluate the extent of the Hg geochemical anomaly arising in the Amiata and Tolfa complex to the coastal area of northern Latium and to examine the possible influence on this area by the Mignone River, and by the small coastal basins, which are characterized by both previous mining activities and decades of past industrial impact. The results confirm the extension of the anomaly of concentrations of Hg in the coastal area of northern Latium, with the northern sector influenced by the contributions of the Fiora and Mignone Rivers and the southern sector influenced by the contributions of minor basins. The results show high values of the Adverse Effect Index throughout the considered area and highlight the need for further investigation in order to assess the impact of human activities on the present and past values of Hg in marine sediments. PMID- 26994619 TI - The complex link of the environment on allergic rhinitis and atopic dermatitis. PMID- 26994620 TI - Mucosal-associated invariant T cells in clinical diseases. AB - Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial infection via vitamin metabolites. The discovery of MAIT cells in the past two decades and the recent discovery of MR1 ligands has opened a new field and potential area for cellular immunotherapy using these unique cells. Their evolutionary conservation in mammals underscore their biological role in the host. In the past two years, we have been involved in the generation of MR1 tetramers as a tool for identification of these cells. Many groups have studied the role of these cells in clinical diseases. OBJECTIVE: Here, we provide an up-to-date comprehensive review of clinical disease that have been studied with regards to MAIT cells. RESULTS: Original articles and review articles under the topic of MAIT cells and their relation to clinical diseases, both in human and animal models were included in the review. CONCLUSION: MAIT cells are potential candidates for future cellular immunotherapy. However, more understanding of the biological role of MAIT cells need to be elucidated first. PMID- 26994621 TI - An association and meta-analysis study of 4 SNPs from beta-2 adrenergic receptor (ADRB2) gene with risk of asthma in children. AB - BACKGROUND: Although various case-control studies have been conducted to investigate the relationship between ADRB2 gene polymorphisms and asthma risk in different population groups, the results have been conflicting and inconclusive. OBJECTIVE: We performed a case-control study to investigate the association of 4 SNPs in the ADRB2 gene with risk of asthma in children, and then conducted a meta analysis by combining the previous studies. METHODS: A total of 340 patients and 340 age-matched healthy controls were recruited. All of the subjects were genotyped using the PCR-based invader assay. The case-control study was performed to define the contribution of rs1042713, rs1042714, rs1800888, and rs1042711 to the predisposition of asthma. Additionally, we further conducted a meta-analysis of the study findings together with those of previously reported studies. RESULTS: No significant association was found between the polymorphisms rs1042713, rs1042714, rs1800888, and rs1042711 and asthma in the current case control study. The meta-analysis confirmed that there was no positive association of these SNPs with asthma in children in Asia, South America, Europe and the overall population. CONCLUSIONS: None of the four polymorphisms in ADRB2 gene were associated with a risk of asthma in a current children population. PMID- 26994622 TI - Association between environmental factors and hospital visits among allergic patients: A retrospective study. AB - OBJECTIVE: This study investigated correlations between meteorological and environmental factors (MEFs) and allergic rhinitis in childhood (ARC). METHODS: Children who received treatment for AR and meteorological data that might have influenced AR in the same time period were included in this study. Daily average maximum values of sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter (PM10) at 3 a.m. and 8 a.m. were provided by the Shanghai Environmental Bureau for statistical analysis using a generalized additive model (GAM). RESULTS: Outpatient visits for ARC were higher, with a bimodal shape, for daily average temperatures of about 11 degrees C and 21 degrees C. However, increasing humidity was associated with a downward trend in outpatient visits for ARC, suggesting that high humidity had a protective effect on AR. When levels of air pollutants such as O3, SO2, and PM10 increased by 10 MUg/m3, AR outpatient visits increased by 1.95%, 1.19% and 0.33%, respectively, suggesting that air pollution might increase the risk of AR episodes. CONCLUSIONS: MEFs were significantly correlated with the incidence of ARC. PMID- 26994623 TI - The effectiveness of oxymetazoline plus intranasal steroid in the treatment of chronic rhinitis: A randomised controlled trial. AB - BACKGROUND: The recommended drug for moderate to severe chronic rhinitis is intranasal steroids (INS). However, nasal congestion could be refractory and need additional treatments. OBJECTIVE: We sought to explore the benefit of oxymetazoline (Oxymet) plus INS on nasal congestion without inducing rhinitis medicamentosa. METHODS: We performed a 60-week, randomised, double-blind clinical trial in 50 patients, 18 years of age or greater, with chronic rhinitis who had used INS and cetirizine and still had nasal congestion. Subjects were randomised to receive 2 sprays of 0.05% Oxymet in each nostril twice daily or placebo for 4 weeks. All patients received 2 sprays of budesonide (100 MUg/spray) in each nostril twice daily and 10 mg cetirizine once daily from entry throughout the study. Nasal symptom scores, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life (Rcq) scores were measured. RESULTS: Oxymet significantly reduced nasal congestion in subjects with chronic rhinitis compared with placebo on the day of 15-28 and 29-42. In subjects with allergic rhinitis, nasal congestion scores in the Oxymet group were significantly reduced compared with those in the placebo group on days 4-7, days 8-14, days 15-28 and days 29 42. In the Oxymet group, post hoc analysis showed that subjects with allergic rhinitis significantly improved their nasal congestion scores compared to non allergic individuals (N, allergic/non-allergic = 18/7, p < 0.05). The combination of INS and Oxymet was not associated with rhinitis medicamentosa. CONCLUSIONS: The combination of INS and Oxymet provides additional benefit compared to INS monotherapy in relieving nasal congestion in subjects with chronic rhinitis and allergic rhinitis without developing rhinitis medicamentosa. PMID- 26994624 TI - A preliminary study of intranasal epinephrine administration as a potential route for anaphylaxis treatment. AB - BACKGROUND: The intranasal (IN) administration of epinephrine could be an alternative route for anaphylaxis treatment. Although IN epinephrine absorption has been demonstrated in animals, such data in humans are still lacking. OBJECTIVE: To study the pharmacokinetics of IN epinephrine absorption in humans. METHODS: Each healthy adult (n = 5) was administered IN saline, IN epinephrine at various doses (i.e., 0.3, 0.6, 1.25, 2.5 and 5 mg), and intramuscular (IM) epinephrine at 0.3 mg. Plasma epinephrine levels at baseline and various time points up to 120 minutes after administration were determined using high performance liquid chromatography with electrochemical detection. RESULTS: Significant systemic absorption of epinephrine via IN route was observed only at the dose of 5 mg, and the absorption thereof was comparable to that of IM epinephrine; the average area-under-curve (AUC) values at 0-120 minutes for IN saline, IM epinephrine, and 5 mg IN epinephrine were 0.3, 18.3, and 19.4 ng.min/mL, respectively. In addition, the peak epinephrine concentrations and the time to reach them were also not significantly different between IM and 5-mg IN epinephrine; the corresponding values (mean +/- SD) were 309 +/- 88 pg/mL and 67 +/- 43 min for IM epinephrine, and 386 +/- 152 pg/mL and 70 +/- 17 min for 5 mg IN epinephrine. CONCLUSION: This preliminary study showed that epinephrine can be significantly absorbed via the IN route in humans. However, it requires a higher IN dose (5 mg) than the usual IM dose (0.3 mg) to achieve comparable systemic epinephrine absorption. PMID- 26994625 TI - Anaphylactic reactions in adult patients in Southern Israel. AB - BACKGROUND: Southern Israel is inhabited by Jews and Bedouins. Children from these populations differ in the epidemiology of anaphylactic reactions; however, the effects of ethnicity on the epidemiology of anaphylactic reactions in adults in these populations are unknown. METHODS: Retrospective review of medical records of patients with anaphylactic reactions treated in a single institution during 2008-2012. RESULTS: A total of 192 evaluable cases of anaphylaxis were recorded; 155 (80.7%) anaphylactic reactions occurred in Jews and 37/192 (19.3%) occurred in Bedouins. A trend towards an older mean age of occurrence of anaphylaxis was recorded in Jewish patients compared with Bedouin patients: 48.1 years versus 41.2, respectively (P = 0.053). Anaphylaxis was more common in Jewish female patients than males and more common in Bedouin male patients than females. Overall, 93/155 (60.0%) females in Jewish patients were affected compared with 14/37 (37.8%) in the Bedouin population (P = 0.015). More Jewish patients had more anaphylaxis attributed to food compared with Bedouin patients: 31/155 (20%) versus 2/37 (5.4%) (P = 0.034). The mean yearly incidence of anaphylaxis was similar in Bedouin and Jewish patients: 12.1 +/- 5.3 versus 17.6 +/- 15.3, respectively (P = 0.466). However, a significant trend towards a higher incidence of anaphylactic reactions was recorded throughout the study years only in Jewish patients (r = 0.906, P = 0.034). CONCLUSIONS: Adult Jewish patients have a significantly higher probability of having anaphylactic reactions due to food compared with Bedouin patients, with females being more affected, and the incidence of anaphylactic reaction is increasing only in the Jewish population. The epidemiology of anaphylactic reactions can differ between populations residing in the same geographical area. PMID- 26994626 TI - Allergenicity of native and recombinant major allergen groups 1 and 2 of Dermatophagoides mites in mite sensitive Thai patients. AB - BACKGROUND AND OBJECTIVE: Natural allergenic extracts using for diagnosis and immunotherapy may have batch-to-batch variations and contaminations with unrefined allergens or non-allergenic components. Thus, recombinant allergen is believed to overcome these shortcomings. In this study, native and recombinant allergens of group 1 and 2 of Dermatophagoides mites were produced and their allergenicities were compared. METHODS: Native allergens were prepared by MAb affinity chromatography. All recombinant allergens were produced in E. coli expression system. IgE reactivities of these allergens were determined by IgE ELISA. RESULTS: The native and recombinant Der p 1, Der p 2, Der f 1, Der f 2 had molecular weights of approximately 25, 15, 25 and 15 kDa, respectively. IgE reactivities of nDer p 1, nDer f 1, rDer p 1 and rDer f 1 were 96.67%, 90%, 43.33% and 46.67%, respectively. Allergenicities of nDer p 2, nDer f 2, rDer p 2 and rDer f 2 were 86.67%, 96.43%, 76.67% and 89.29%, respectively. The findings indicated that recombinant group-1 products were minor allergens which revealed no correlation with their native forms. In contrast, recombinant group-2 allergens were major allergens and showed a significant correlation to their native allergens. CONCLUSION: We successfully produced native and recombinant group-1 and group-2 allergens. According to their allergenicities, recombinant Der p 2 and rDer f 2 have potential to replace native allergen in diagnostic and therapeutic extracts. Moreover, they can employ as a standard reagent to measure the amount of group 2 allergen in the environment by sandwich-ELISA and utilise this as an immunogen for MAb production. PMID- 26994627 TI - Provocation proven drug allergy in Thai children with adverse drug reactions. AB - BACKGROUND: Adverse drug reactions (ADRs) are a common healthcare problem. The drug provocation test (DPT) is a gold standard for ADR diagnosis. OBJECTIVES: To evaluate a correlation between history of ADRs, skin prick test (SPT), intradermal test (ID) and DPT in Thai children. METHODS: This was a retrospective review of 211 children under 16 years of age who had a history of ADRs and underwent DPT from January 2006 to December 2012. RESULTS: Two hundred and thirty six (236) DPTs were performed in 211 children with a history of ADRs. The median age at which DPTs were performed was 4 years. Thirty-four children (14.4%) had positive DPT. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, likelihood ratio (LR) + and LR- of SPT were 50, 85.7, 6.9, 98.8%, 5.8 and 0.9, respectively. The PPV, NPV, sensitivity, specificity, LR+ and LR- of ID were 33.3, 84.6, 20, 91.7%, 2.4 and 0.9, respectively. Different presentation of symptoms (maculopapular rashes, urticaria, angioedema and anaphylaxis) did not predict SPT, ID and DPT results. Positive human immunodeficiency virus (HIV), but not atopy, was a risk in the present scope of evaluation for drug allergy (odds ratio 11.44, 95% confidence interval 2.60-50.41). CONCLUSION: Drug allergy, denoted by positive DPT, was present in 14.4% of Thai children with a history of ADRs. Antibiotics were the most common cause of ADRs. Both SPT and ID had high NPV and specificity but did not predict DPT results. HIV positivity is a risk factor of drug allergy in Thai children. PMID- 26994628 TI - Risk factors of atopic dermatitis in Korean schoolchildren: 2010 international study of asthma and allergies in childhood. AB - BACKGROUND & OBJECTIVE: We aimed to analyse the risk factors of atopic dermatitis (AD) in Korean schoolchildren in 2010. METHODS: A nationwide, cross-sectional study was conducted in children aged 6-7 years and adolescents aged 12-13 years who were randomly selected. Information was obtained through a Korean version of the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC), and skin prick tests were performed. AD-diagnosed children were selected for risk factor analysis by using logistic regression. RESULTS: We enrolled 4,003 children (M/F = 2,021/ 1,982) in aged 6-7 years and 4,112 children (M/F = 2,029/2,083) in 12-13 years. In children aged 6-7 years, the lifetime prevalence of AD diagnosis was 35.6% (N = 1,424). On the other hand, in the 12 to 13 year age group, the lifetime prevalence of AD diagnosis was 24.2% (N = 981). In the univariate logistic regression analysis in 6-7 year-old children, possible risk factors were atopy, a parental history of allergic disease, the use of antibiotics during infancy, a history of having moved into a newly built house during infancy, the presence of visible mould in the house, and remodelling of house within 12 months. The statistical significance persisted after adjustment. However, antibiotic use during infancy and remodelling within 12 months showed no statistical significance as a risk factor for AD. In contrast, multivariate logistic regression analysis in adolescents demonstrated that female sex, atopy, a parental history of allergic diseases, the presence of visible mould in the house, and a history of having moved into a newly built house during infancy was associated with AD. There was no significant association between AD and other risk factors. CONCLUSION: In Korean schoolchildren, risk factors such as atopy, the presence of parental allergic diseases, moving into a newly built house during infancy and visible mould in the house were associated with AD. PMID- 26994629 TI - HAX-1 deficiency: Characteristics of five cases including an asymptomatic patient. AB - BACKGROUND: Mutations in the HAX-1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN), which particularly manifests with recurrent skin, lung and deep tissue infections from the first few months of life. OBJECTIVE: We retrospectively evaluated the clinical and laboratory findings of the patients diagnosed with SCN carrying HAX1 gene mutations. METHODS: A total of five patients with SCN, carrying a HAX1 gene mutation, were evaluated in terms of clinical and laboratory findings. Mutation analysis of the candidate genes (HAX1, ELANE and CSF3R) was performed. RESULTS: All of the patients lived in Turkey; four of them were of Kurdish origin and one was Turkish. Of the five patients, three were girls and two were boys, and the mean age of the patients was 8.8 years old (range 4-15 years). The mean age of diagnosis was 25.8 months (range 2 months-5 years). The infections diagnosed included recurrent gingivitis, stomatitis, and skin and soft tissue abscesses. Developmental retardation and epilepsy were present in only one patient, whereas speech retardation was present in two. All of our patients had a HAX1 mutation, and are still alive and none of them has shown malignant transformation yet. CONCLUSION: Complete blood count should be performed and absolute neutrophil count should be evaluated in patients with recurrent severe infections. In the event that neutropenia is detected, they should be investigated in terms of SCN and mutation analysis should be performed. PMID- 26994630 TI - Autophagy machinery impaired interferon signalling pathways to benefit hepatitis B virus replication. AB - BACKGROUND: Autophagy-related genes ATG4B, ATG7, and ATG12 have been identified to play a critical role in viral replication. However, these genes have yet to be identified in hepatitis B virus (HBV). OBJECTIVE: To characterise the role of ATG4B, ATG7, and ATG12 genes in HBV infection. METHODS: The mRNA expression was examined by quantitative real-time RT-PCR and Western blotting. Short hairpin RNA (shRNA) of the target gene was used to examine the function of the gene in HBV replication. Evaluation of HBV DNA level was performed by real-time PCR. RESULTS: Our findings revealed that ATG12 gene expression was significantly up-regulated (p < 0.005), whereas ATG7 gene expression was down-regulated (p < 0.0001) in HepG2.2.15 cells when compared to HepG2 cells. However, no significant difference in mRNA level of ATG4B was observed. These results were consistent with protein level findings. Moreover, we analysed the function of ATG12 in HBV replication by using ATG12 shRNA and evaluated HBV DNA level. We found that the amount of HBV was decreased in ATG12-knockdown HepG2.2.15 cells when compared to control HepG2.2.15 cells (P < 0.05). The mRNA expression of interferon-alpha (IFN-alpha), interferon-beta (IFN-beta), and interferon-inducible genes (IFI) was also investigated. Our results showed that the expression of IFN-alpha, IFN-beta, and IFI27 genes were increased in ATG12-knockdown cells but not in Mx1 gene when compared to control cells (p < 0.005, p < 0.0001 and p < 0.005, respectively). CONCLUSION: These autophagy-related genes, ATG12 may play a role in HBV replication via impairing IFN pathway. However, the biological significance of other autophagic genes such as ATG7 warrants further study. PMID- 26994631 TI - Association between flow cytometric crossmatching and graft survival in Thai cadaveric-donor kidney transplantation. AB - BACKGROUND: The flow cytometry cross-match (FCXM) technique is a sensitive method and has been reported to predict and protect graft rejection more efficiently than the conventional complement-dependent cytotoxicity cross-match (CDCXM) and the anti-human globulin-complement dependent cytotoxicity (AHG-CDC) methods. METHODS: We performed retrospective FCXM in 270 cadaveric donor kidney transplant patients with negative CDC and AHG. The correlation between FCXM with graft rejection and graft survival within 1 year to 3 years was analysed. RESULTS: There were 97 (35.9%) samples with positive FCXM. Only 7 (2.6%) of the 270 samples had evidence of antibody-mediated rejection (AMR) at the first year, which increased to 10 (3.7%) AMR samples after 3 years. Interestingly, there was a significant association between FCXM results with the graft outcome at 1 year (P = 0.046). However, when the association was analysed at 3 years after transplantation, it did not reach statistical significance. FCXM detected concordant positive results in 4 out of 8 samples. These samples had mean fluorescence intensity (MFI) of the donor-specific antibody (DSA) higher than 2,000. The DSA was identified by a single antigen bead. CONCLUSION: Although positive FCXM, particularly for HLA class I, was significantly associated with graft loss from AMR within 1 year of transplantation in this study, there were a lot of FCXM false positives, as high as 35.9%. Additional studies are required to further assess the usefulness of FCXM in Thailand. PMID- 26994632 TI - Erratum: Renin angiotensin system blockers-associated angioedema in the Thai population. PMID- 26994633 TI - Complement and Humoral Adaptive Immunity in the Human Choroid Plexus: Roles for Stromal Concretions, Basement Membranes, and Epithelium. AB - The choroid plexus (CP) provides a barrier to entry of toxic molecules from the blood into the brain and transports vital molecules into the cerebrospinal fluid. While a great deal is known about CP physiology, relatively little is known about its immunology. Here, we show immunohistochemical data that help define the role of the CP in innate and adaptive humoral immunity. The results show that complement, in the form of C1q, C3d, C9, or C9neo, is preferentially deposited in stromal concretions. In contrast, immunoglobulin (Ig) G (IgG) and IgA are more often found in CP epithelial cells, and IgM is found in either locale. C4d, IgD, and IgE are rarely, if ever, seen in the CP. In multiple sclerosis CP, basement membrane C9 or stromal IgA patterns were common but were not specific for the disease. These findings indicate that the CP may orchestrate the clearance of complement, particularly by deposition in its concretions, IgA and IgG preferentially via its epithelium, and IgM by either mechanism. PMID- 26994634 TI - Early supportive medication use and end-of-life care among Medicare beneficiaries with advanced breast cancer. AB - PURPOSE: A randomized controlled trial of cancer patients has linked early supportive care with improved hospice use and less-aggressive end-of-life care. In practice, the early use of supportive interventions and potential impact on end-of-life care are poorly understood. We sought to describe early use of medications to treat common breast cancer symptoms (pain, insomnia, anxiety, and depression) and to assess the relationship between early use of these treatments and end-of-life care. METHODS: Secondary analysis of 2006-2012 SEER-Medicare data was performed. Women included had stage IV breast cancer and died within the observation period. We used modified Poisson regression to assess the relationship between supportive medication use in the 90 days post-diagnosis and several end-of-life care measures (hospice use, in-hospital death, chemotherapy receipt within 14 days of death, ICU admission, or >1 hospitalization or emergency department/ED visit 30 days before death). RESULTS: Among the 947 women included, 68 % of women used at least one supportive medication in the 90 days following their diagnosis: 60.3 % used opioid pain medications and 28.3 % received non-opioid psychotropic medications. Early use of any supportive medications was not associated with end-of-life care. Similarly, we found no differences in end-of-life care between opioid pain medication users and non users. However, we found that non-opioid psychotropic medication users were less likely to receive chemotherapy in the last 14 days of life (aRR 0.33, 95 % CI 0.12-0.88). CONCLUSIONS: Non-opioid psychotropic use was associated with some aspects of end-of-life care. Future research should consider alternative measures of palliative and supportive care use using administrative data sources. PMID- 26994635 TI - Goal-Directed Fluid Therapy on Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients. AB - BACKGROUND: In bariatric surgery, there are no guidelines available for intraoperative fluid administration. Goal-directed fluid therapy (GDFT) is a new concept of perioperative fluid management that has been shown to improve the prognosis of patients undergoing abdominal surgery. The aim of our study is to assess the impact of the implementation of a GDFT protocol in morbidly obese patients who underwent laparoscopic sleeve gastrectomy (LSG). METHODS: A before after intervention study, in morbidly obese patients who underwent LSG, was conducted at the Obesity Unit of the General University Hospital Elche. Data from the GDFT implementation group (January 2014 to December 2015) were prospectively collected and compared with a preimplementation group (January 2012 to December 2013). RESULTS: Baseline demographic and comorbidity data between the two groups of patients were similar. The length of stay in the hospital was significantly shortened in GDFT group from 4.5 to 3.44 days (p < 0.001). Intraoperative fluid administration was significantly lower in the GDFT group (1002.4 vs 1687.2 ml in preimplementation group, p < 0.001). In the postoperative period, there was a statistically significant reduction in postoperative nausea and vomiting (PONV) after GDFT implementation (48 to 14.3 %, p < 0.001). CONCLUSIONS: Implementation of GDFT protocols can prevent intraoperative fluid overload in patients undergoing bariatric surgery. It could improve outcomes, for example decreasing PONV or even hospital stay. PMID- 26994636 TI - Perioperative Online Weight Monitoring in Bariatric Surgery with a Digital Internet-Connected Scale. AB - INTRODUCTION: Strict follow-up after bariatric surgery is an important factor in achieving and maintaining weight loss, whereas regaining weight is the most important threat in long-term follow-up. Stagnation in weight loss or weight regain can be signals of early treatment failure. The aim of this study is to assess the possibility of obtaining frequent objective weight measurements using an Internet-connected home weighing scale. METHODS: Internet-connected home weighing scales were used to perform weekly follow-up in bariatric surgery patients during the first postoperative year. For each patient, weight measurements were registered and excess body weight loss was calculated. This follow-up method was deemed successful if weight measurements were available for 80% of all weeks in the first year. RESULTS: A total of 14 patients started the protocol. Seven patients (50%) performed weekly weight measurements for at least 80% of all weeks in the first year. One-year follow-up was available for 11 patients. Excess weight loss was >50% in nine (82%) of these patients and >40% in the remaining two. CONCLUSIONS: Using an Internet-connected weighing scale at home is feasible in postsurgery bariatric patients. It can provide the treating physicians with valuable information about weight loss over time. This could possibly offer opportunities for timely interventions during follow-up in case of insufficient weight loss or weight regain. PMID- 26994637 TI - Science and Scaremongering. PMID- 26994638 TI - Thiadiazole derivatives as New Class of beta-glucuronidase inhibitors. AB - Thiadiazole derivatives 1-24 were synthesized via a single step reaction and screened for in vitro beta-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC50=2.16 +/- 0.01 58.06 +/- 1.60 MUM as compare to standard d-saccharic acid 1,4-lactone (IC50=48.4 +/- 1.25 MUM). Molecular docking study was conducted in order to establish the structure-activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques (1)H, (13)C NMR, and EIMS. PMID- 26994639 TI - Human VDAC isoforms differ in their capability to interact with minocycline and to contribute to its cytoprotective activity. AB - It has been previously demonstrated that cytoprotective activity displayed by minocycline in the case of the yeast Saccharomyces cerevisiae cells pretreated with H2O2 requires the presence of functional VDAC (YVDAC1). Thus, we decided to transform YVDAC1-depleted yeast cells (Deltapor1 cells) with plasmids expressing human VDAC isoforms (HVDAC1, HVDAC2, HVDAC3) to estimate their involvement in the minocycline cytoprotective effect. We observed that only expression of HVDAC3 in Deltapor1 cells provided minocycline-mediated cytoprotection against H2O2 although all human isoforms are functional in Deltapor1 cells. The observation appears to be important for on-going discussion concerning VDAC isoform roles in mitochondria and cell functioning. PMID- 26994640 TI - Episodic positive selection at mitochondrial genome in an introduced biological control agent. AB - Artificial introduction in classical biological control provides a unique opportunity to understand mitochondrial evolution driving adaptation to novel environments. We studied mitochondrial genomes of a world-wide introduced agent, Cryptolaemus montrouzieri. We detected positive selection in complex I genes (ND5 and ND4) against a background of widespread negative selection. We further detected significant signals in neutrality tests within 11 populations at ND5 gene, indicating a recent selective sweep/positive selection. Our results imply that these candidate mutations may contribute local adaptation of exotic biological control agents and these provide new insights into the improvement of classical biological control programs. PMID- 26994641 TI - Computer Vision Tool and Technician as First Reader of Lung Cancer Screening CT Scans. AB - OBJECTIVES: To implement a cost-effective low-dose computed tomography (LDCT) lung cancer screening program at the population level, accurate and efficient interpretation of a large volume of LDCT scans is needed. The objective of this study was to evaluate a workflow strategy to identify abnormal LDCT scans in which a technician assisted by computer vision (CV) software acts as a first reader with the aim to improve speed, consistency, and quality of scan interpretation. METHODS: Without knowledge of the diagnosis, a technician reviewed 828 randomly batched scans (136 with lung cancers, 556 with benign nodules, and 136 without nodules) from the baseline Pan-Canadian Early Detection of Lung Cancer Study that had been annotated by the CV software CIRRUS Lung Screening (Diagnostic Image Analysis Group, Nijmegen, The Netherlands). The scans were classified as either normal (no nodules >=1 mm or benign nodules) or abnormal (nodules or other abnormality). The results were compared with the diagnostic interpretation by Pan-Canadian Early Detection of Lung Cancer Study radiologists. RESULTS: The overall sensitivity and specificity of the technician in identifying an abnormal scan were 97.8% (95% confidence interval: 96.4-98.8) and 98.0% (95% confidence interval: 89.5-99.7), respectively. Of the 112 prevalent nodules that were found to be malignant in follow-up, 92.9% were correctly identified by the technician plus CV compared with 84.8% by the study radiologists. The average time taken by the technician to review a scan after CV processing was 208 +/- 120 seconds. CONCLUSIONS: Prescreening CV software and a technician as first reader is a promising strategy for improving the consistency and quality of screening interpretation of LDCT scans. PMID- 26994642 TI - Evaluation of Computer-Based Training for Health Workers in Echocardiography for RHD. AB - BACKGROUND: The implementation of screening for rheumatic heart disease at a population-scale would require a considerable increase in human resources. Training nonexpert staff in echocardiography requires appropriate methods and materials. OBJECTIVES: This pre/post study aims to measure the change in the knowledge and confidence of a group of health workers after a computer-assisted training intervention in basic echocardiography for rheumatic heart disease. METHODS: A syllabus of self-guided, computer-based modules to train nonexpert health workers in basic echocardiography for rheumatic heart disease was developed. Thirty-eight health workers from Uganda participated in the training. Using a pre/post design, identical test instruments were administered before and after the training intervention, assessing the knowledge (using multiple-choice questions) and confidence (using Likert scale questions) in clinical science and echocardiography. RESULTS: The mean total score on knowledge tests rose from 44.8% to 85.4% (mean difference: 40.6%, 95% confidence interval [CI]: 35.4% to 45.8%), with strong evidence for an increase in scores across all knowledge theme areas (p < 0.001). Increased confidence with each key aspect was reported, and there was strong evidence for an increase in the mean score for confidence scales in clinical science (difference: 7.1, 95% CI: 6.2 to 8.0; p < 0.001) and echocardiography (difference: 18.3, 95% CI: 16.6 to 20.0; p < 0.001). CONCLUSIONS: The training program was effective at increasing knowledge and confidence for basic echocardiography in nonexpert health workers. Use of computer-assisted learning may reduce the human resource requirements for training staff in echocardiography. PMID- 26994643 TI - Time Trends in Lifestyle, Risk Factor Control, and Use of Evidence-Based Medications in Patients With Coronary Heart Disease in Europe: Results From 3 EUROASPIRE Surveys, 1999-2013. AB - BACKGROUND: The EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) cross-sectional surveys describe time trends in lifestyle and risk factor control among coronary patients between 1999 and 2013 in Belgium, Czech Republic, Finland, France, Ireland, the Netherlands, Poland, Slovenia, and the United Kingdom as part of the EuroObservational Research Programme under the auspices of European Society of Cardiology. OBJECTIVES: This study sought to describe time trends in lifestyle, risk factor control, and the use of evidence-based medication in coronary patients across Europe. METHODS: The EUROASPIRE II (1999 to 2000), III (2006 to 2007), and IV (2012 to 13) surveys were conducted in the same geographical areas and selected hospitals in each country. Consecutive patients (<=70 years) after coronary artery bypass graft, percutaneous coronary intervention, or an acute coronary syndrome identified from hospital records were interviewed and examined >=6 months later with standardized methods. RESULTS: Of 12,775 identified coronary patients, 8,456 (66.2%) were interviewed. Proportion of current smokers was similar across the 3 surveys. Prevalence of obesity increased by 7%. The prevalence of raised blood pressure (>=140/90 mm Hg or >=140/80 mm Hg with diabetes) dropped by 8% from EUROASPIRE III to IV, and therapeutic control of blood pressure improved with 55% of patients below target in IV. The prevalence of low-density lipoprotein cholesterol >=2.5 mmol/l decreased by 44%. In EUROASPIRE IV, 75% were above the target low-density lipoprotein cholesterol <1.8 mmol/l. The prevalence of self reported diabetes increased by 9%. The use of evidence-based medications increased between the EUROASPIRE II and III surveys, but did not change between the III and IV surveys. CONCLUSIONS: Lifestyle habits have deteriorated over time with increases in obesity, central obesity, and diabetes and stagnating rates of persistent smoking. Although blood pressure and lipid management improved, they are still not optimally controlled and the use of evidence-based medications appears to have stalled apart from the increased use of high-intensity statins. These results underline the importance of offering coronary patients access to modern preventive cardiology programs. PMID- 26994644 TI - Broncho-biliary fistula secondary to biliary obstruction and lung abscess in a patient with pancreatic neuro-endocrine tumor. AB - We present a case report of broncho-biliary fistula that developed due to the blockage of biliary stent placed during the management of pancreatic neuroendocrine tumor (pNET); diagnosed on high clinical suspicion, percutaneous cholangiogram and contrast enhanced computed tomography (CECT); and successfully treated with percutaneous transhepatic biliary drainage (PTBD). PMID- 26994645 TI - Altered fractionation radiotherapy in head and neck squamous cell carcinoma. AB - INTRODUCTION: Fractionation plays a pivotal role in determining the effectiveness of radiation and follows the principle of 4 "R" of radiobiology. The various altered fractionation schedules used are hyper-fractionation, accelerated fractionation, and hypo fractionation. METHODS: We reviewed the landmark articles published in the peer reviewed journals to summarize the beneficial role of altered fractionation in the treatment of head and neck carcinoma. RESULTS: Hyper fractionation definitely gives very good overall survival benefit for locally advanced head and neck patient's equivalent to survival benefit to that of concurrent chemoradiotherapy. Adding concomitant chemotherapy to altered fractionation is a logical approach to improve survival in locally advanced head and neck cancer patients, but it may be at a cost of higher toxicity. Mild hypo fractionation may be beneficial in early laryngeal cancers and may help in achieving better local control. CONCLUSION: Altered fractionation is a very important treatment schema and requires the reinforcement of its use. PMID- 26994646 TI - Screening of Mechanical Complications of Dilated Pulmonary Artery Related to the Risk for Sudden Cardiac Death in Patients with Pulmonary Arterial Hypertension by Transthoracic Echocardiography. AB - BACKGROUND: In patients with pulmonary arterial hypertension (PAH), the mechanical complications of pulmonary artery (PA) enlargement are related to sudden cardiac death (SCD). The aim of this study was to investigate the prevalence of PA enlargement, the correlation of main PA (MPA) diameter with other echocardiographic parameters, and the role of transthoracic echocardiography in screening for such complications. METHODS: Among 298 patients who were followed for PAH, patients with PA enlargement (>40 mm) by transthoracic echocardiography were consecutively enrolled in a prospective manner. The presence of left main and airway compression, PA dissection, or PA thrombus was determined with cardiac computed tomography. RESULTS: Forty-six patients (15.4%; mean age, 49 +/- 14 years; 32.6% men) with dilated MPAs were enrolled. Mechanical complications were present in 16 patients (34.8%). Those with complications had more dilated MPAs compared with patients without (mean PA diameter, 55.6 +/- 12.2 vs 46.7 +/- 4.3 mm; P = .012). Other echocardiographic parameters of the right heart, such as right ventricular systolic pressure, showed no differences (P > .05 for all). The area under the receiver operating characteristic curve for MPA diameter was 0.750 (95% CI, 0.577-0.923; P = .009), with the highest sensitivity and specificity values for the presence of complications being 85.7% and 58.6%, respectively, according to an MPA diameter of 46.5 mm. CONCLUSIONS: Mechanical complications related to sudden cardiac death in patients with PAH with dilated PAs are common. The overall performance of transthoracic echocardiography as a screening tool for predicting such complications appears reasonable. Given the burden of sudden cardiac death, measurement of PA diameter should be routinely included over the course of follow-up, especially in patients with PAH. PMID- 26994647 TI - The Thrust Plate Hip Prosthesis: A Follow-Up of 15-20 Years With 102 Implants. AB - BACKGROUND: Between November 1992 and January 1999, a cohort of 102 thrust plate hip prostheses was implanted. METHODS: We now clinically and radiologically evaluate the remaining 73 prostheses with a mean follow-up of 17.2 years. RESULTS: The Harris Hip Score increased from 51.4 points preoperatively to 94.3 points at the time of this follow-up. No further changes in the radiologic findings occurred since the first follow-up, published in 2005, conducted 2-8 years after implantation. Within 15 to 20 years after primary implantation of the 102 prostheses, 6 aseptic loosenings occurred, which correspond to a cumulated survival rate of 94.7% at 17 and 91.8% at 18 years. CONCLUSION: Although the thrust plate hip prostheses is no longer marketed, the biomechanical behaviour of this unique, clinically successful prosthesis deserves attention. PMID- 26994648 TI - Preoperative Risk Factors for, and Incidence of Delayed Surgery in Elective Primary Total Knee Arthroplasty After Hospital Admission: The ACS-NSQIP. AB - BACKGROUND: Approximately 600,000 total knee arthroplasties (TKA) are performed every year in the United States and the number of procedures has increased substantially every year. These demands may further strain the government, insurers, and patients struggling with increasing healthcare spending. A delay in proceeding to surgery after hospital admission may affect the overall healthcare costs. To our knowledge, the current literature has not addressed the incidence of, and preoperative risk factors for, a surgical delay in TKA. METHODS: The ACS NSQIP 2011 database was reviewed to identify patients undergoing elective primary total knee arthroplasty (TKA) using the Current Procedural Terminology (CPT) code 27447. 14,881 cases were no delay in proceeding to surgery after hospital admission while 139 cases were delayed for TKA. Risk factors or comorbidities contributing to surgical delay in TKA were identified. A univariate analysis of all patient parameters was conducted to measure the difference between the two cohorts. Finally, a multivariate logistic regression analysis was then conducted to identify risk factors or comorbidities for surgical delay. RESULTS: There were 139 cases of surgical delay in TKA (0.93%). Congestive heart failure (P = 0.017), bleeding disorder (P <0.0001), sepsis (P <0.0001), a prior operation in the past 30 days (P <0.0001), dependent functional status (P <0.0001), ASA class 3 (P = 0.046), and hematocrit <38% (P <0.0001) were independent risk factors for a surgical delay. Postoperative medical complication (2.2% vs 0.8%, P < 0.0001) in surgical delay was significantly higher than non-delayed cohort. CONCLUSION: The optimization of preoperative modifiable risk factors appears to be one of the best strategies to reduce delayed surgery and therefore costs in TKA. PMID- 26994649 TI - The Relationship Between Hospital Payer Mix and Volume Growth in Total Joint Arthroplasty: A 12-Year Analysis. AB - BACKGROUND: Hospital reimbursement for Medicare/Medicaid/self-pay patients has not kept pace with rising expenses, and even well run efficient organizations struggle to maintain a positive margin on these cases. Therefore, hospitals rely on commercially insured patients to remain economically viable. However, hospitals located in areas with a high Medicare/Medicaid/uninsured population cannot depend on a favorable payer mix for financial sustainability. METHODS: Using the Statewide Planning and Research Cooperative System database, total joint arthroplasties (TJAs) in New York from 2000 to 2012 were identified. Hospitals were divided into quartiles by volume, with quartile 1 representing the lowest volume hospitals. TJA cases were stratified by primary payer type, and the percentage of each primary payer type was calculated and compared among quartiles. RESULTS: The highest number of hospitals performing TJAs was 207 in 2000, and the least number of hospitals was in 2012, with only 178 hospitals performing TJA. Despite the decrease in the number of hospitals, the total number of joint arthroplasties increased from 33,036 in 2000 to 62,104 in 2012. CONCLUSIONS: Our study demonstrates that higher volume hospitals tended to have a more favorable payer mix (less Medicare/Medicaid/self-pay patients). This inequity widened over the 12-year study period. This trend has ethical implications for lower socioeconomic status patients as high-volume centers tend to have superior outcomes compared with low-volume centers. In addition, the lower volume high Medicare/Medicaid/self-pay hospitals are more susceptible to the Center for Medicare and Medicaid Services quality penalties making their economic viability even more tenuous potentially leading to access of care problems for these patients. PMID- 26994650 TI - Morbid Obesity in Total Hip Arthroplasty: Redefining Outcomes for Operative Time, Length of Stay, and Readmission. AB - BACKGROUND: The incidence of obesity among patients presenting for elective total hip arthroplasty (THA) has increased in the last decade, and the relationship between obesity and the need for joint arthroplasty has been demonstrated. This study evaluates the effects of morbid obesity on outcomes after primary THA by comparing short-term outcomes in THA between a morbidly obese (body mass index [BMI] >=40) and a normal weight (BMI, 18.5 to <25) cohort at our institution between January 2003 and December 2010. METHODS: Thirty-nine patients included in the morbidly obese group were compared with 186 in the normal weight group. Operative time, length of stay, complications, readmission, and length of readmission were compared. RESULTS: Operative time was increased in the morbidly obese group at 122 minutes compared with 100 minutes (P = .002). Postoperatively, there was an increased 30-day readmission rate related to surgery of 12.8% associated with BMI >=40 compared with 2.7% (P = .005) as well as a 5.1-fold increase in surgery-related readmitted bed days-0.32 bed days per patient for normal weight compared with 1.64 bed days per patient for the morbidly obese (P = .026). CONCLUSION: Morbidly obese patients present a technical challenge and likely this, and the resultant complications are underestimated. More work needs to be performed to enable suitable allocation of resources. PMID- 26994651 TI - Utility of Serum Inflammatory and Synovial Fluid Counts in the Diagnosis of Infection in Taper Corrosion of Dual Taper Modular Stems. AB - BACKGROUND: An accurate diagnosis of periprosthetic joint infection (PJI) is critical as treatment of the infected total hip arthroplasty differs from aseptic failure. The clinical presentation of PJI may mimic symptoms of taper corrosion. Our aim was to evaluate the utility of serum inflammatory markers and synovial fluid white blood cell (WBC)/differential counts in diagnosis of PJI in failed dual taper total hip arthroplasty due to taper corrosion. METHODS: We retrospectively reviewed 62 dual taper modular stem patients who underwent revision surgery for symptomatic adverse local tissue reaction due to taper corrosion. All patients had preoperative hip synovial aspirations, serum inflammatory markers, metal ion levels, and intraoperative cultures. Using Musculoskeletal Infection Society PJI criteria, we divided the cohort into infected and noninfected groups. Receiver-operating characteristic curves were constructed to determine the relationship and optimal cutoff values for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and synovial fluid counts. RESULTS: Infection group had significantly higher mean ESR (P = .002), CRP (P = .01), synovial fluid WBC (P < .001), and neutrophil percentage (P = .02). Cobalt levels were significantly elevated in noninfection group (P = .02). Using receiver-operating characteristic curve analysis, the most ideal tests for diagnosis of PJI were synovial fluid WBC (area under the curve = 86%, optimal cutoff 730 WBC/uL) and neutrophil percentage (area under the curve = 83%, optimal cutoff 65%). ESR and CRP thresholds of 22 mm/h and 3 mg/L demonstrated 57% sensitivity and 95% specificity and 29% sensitivity and 93% specificity for detection of PJI, respectively. CONCLUSION: Our study suggests that ESR and CRP are useful in excluding PJI in dual taper modular implants with corrosion, whereas both synovial WBC count and neutrophil percentage are useful markers for diagnosing infection. PMID- 26994652 TI - N-acetylgalactosamine glycans function in cancer cell adhesion to endothelial cells: A role for truncated O-glycans in metastatic mechanisms. AB - Failure in O-glycan chain extension exposing Tn antigen (GalNAc-O-Ser/Thr) is clinically associated with cancer metastasis. This study provides evidence of a functional role for aberrant GalNAc-glycans in cancer cell capture from blood flow and/or adhesion to endothelium. Adhesion of breast cancer cells to human umbilical vein endothelial cell monolayers was modelled under sweeping flow. Adhesion of metastatic, GalNAc glycan-rich, MCF7 and ZR 75 1 cells to endothelium increased over timepoints up to 1.5 hour, after which it plateaued. Adhesion was significantly inhibited (p < 0.001) when cell surface GalNAc-glycans were masked, an effect not seen in GalNAc glycan-poor, non-metastatic BT 474 cells. Masking irrelevant galactose- and mannose-glycans had no inhibitory effect. Imaging of cells post-adhesion over a 24 hour time course using confocal and scanning electron microscopy revealed that up to 6 hours post-adhesion, motile, rounded cancer cells featuring lamellipodia-like processes crawled on an intact endothelial monolayer. From 6-12 hours post-adhesion, cancer cells became stationary, adopted a smooth, circular flattened morphology, and endothelial cells retracted from around them leaving cleared zones in which the cancer cells proceeded to form colonies through cell division. PMID- 26994653 TI - Genetic variation of the 20 STRs in Han population from Yunnan-Kweichow plateau of China. PMID- 26994654 TI - A proposal to reduce the risk of transmission of human papilloma virus via transvaginal ultrasound. AB - Three steps must be followed to prevent the transmission of infection via a contaminated transvaginal ultrasound probe: cleaning the probe after every use, high-level disinfection, and covering the probe with a single-use barrier during the examination. There may be critical flaws in at least 2 of these steps as they are currently practiced. First, 2 widely used disinfectants, glutaraldehyde and orthophthalaldehyde, have recently been found to be ineffective at neutralizing human papilloma virus type 16 and type 18. Second, commercial ultrasound probe covers have an unacceptable rate of leakage (8-81%) compared to condoms (0.9-2%). We recommend the use of a sonicated hydrogen peroxide disinfectant system rather than aldehyde-type disinfectants. We recommend that the probe be covered with a condom rather than a commercial probe cover during transvaginal ultrasound examination. Combined with probe cleaning, these 2 steps are estimated to result in an 800 million- to 250 billion-fold reduction in human papilloma virus viral load, which should translate to greatly enhanced patient safety. PMID- 26994655 TI - Is a history of preeclampsia associated with an increased risk of a small for gestational age infant in a future pregnancy? AB - BACKGROUND: A history of preeclampsia is associated with an increased risk of subsequent preeclampsia, but it is unclear whether women with prior preeclampsia are at increased risk of having a small-for-gestational-age infant in their subsequent pregnancy, even if they do not develop preeclampsia. OBJECTIVE: The objective of this study was to evaluate whether women with preeclampsia in a prior pregnancy are at increased risk of having a pregnancy complicated by a small-for-gestational-age infant, even in the absence of recurrent preeclampsia. STUDY DESIGN: This was a secondary analysis of data from 2 multicenter, randomized controlled trials evaluating the role of aspirin in preeclampsia prevention in healthy nulliparas and women at high risk of preeclampsia (ie, with chronic hypertension or a history of preeclampsia). Women who developed preeclampsia in a subsequent pregnancy and women with pregestational diabetes or with a multiple gestation were excluded. The association between a history of preeclampsia and the subsequent birth of a small-for-gestational-age infant was determined in both a univariable and multivariable analysis. RESULTS: A total of 4052 women were included in the analysis: 2972 healthy nulliparas, 499 women with a history of preeclampsia, and 581 women with chronic hypertension. The frequency of delivery of a small-for-gestational-age infant significantly differed by clinical history (5.1% vs 9.2% vs 12.1% in healthy nulliparas, women with a history of preeclampsia, and women with chronic hypertension, respectively, P < .001). Compared with healthy nulliparas, a history of preeclampsia was associated with a significantly increased odds for a small-for-gestational-age infant, even if recurrent preeclampsia did not occur (adjusted odds ratio, 1.48, 95% confidence interval, 1.02-2.17). CONCLUSION: Even in the absence of recurrent preeclampsia, women with a history of preeclampsia are at a higher risk of delivering a small-for-gestational-age infant in a subsequent pregnancy. PMID- 26994656 TI - [Gender violence: Knowledge and attitudes of nurses in Primary Care]. AB - AIM: To determine the knowledge and attitudes of nurses in Primary Care as regards gender violence and their relationship with socio-demographic factors and cases detected. DESIGN: Cross-sectional, descriptive study. LOCATION: Urban health centres. PARTICIPANTS: A total of 167 nurses working in Primary Care. MAIN MEASUREMENTS: A questionnaire was used that included questions related to knowledge, knowledge perception and attitudes to gender violence attitudes. Variables such as age, gender, marital status, work place and health area were also analysed. RESULTS: The response rate was 114 (68.26%). The percentage of correct responses in the knowledge questions was 62.2%, with a medium level of knowledge being observed. Married nurses or couples living in a stable relationship obtained a higher score (95.2%, P=.077). The low detection (29%) is associated with marital status (P=.004), low knowledge (P=0,008), low knowledge perception (P=.001), lack of training (P=.03) and non-implementation of the gender violence protocol (P=.001). Nurses with low self-perception of their knowledge implement the protocol less often (OR=0.26; 95% CI: 0.1-0.7), and they consider that the lack of training is the main problem in determining the diagnosis (OR=11.24; 95% CI: 1.5-81.1). CONCLUSIONS: The level of knowledge was adequate. Nurses have a lack of confidence in terms of their knowledge about gender violence. The detection and diagnosis attitudes are more related to self perception of levels of knowledge than their real knowledge. Marital status influences the level of knowledge. Professionals state that the lack of training is the main problem to give an efficient healthcare response. PMID- 26994657 TI - A Glimpse beyond Structures in Auxin-Dependent Transcription. AB - Auxin response factors (ARFs), transcription factors (TFs), and their Aux/IAA (IAA) repressors are central components of the auxin signalling pathway. They interact as homo- and heteromultimers. The structure of their interacting domains revealed a PB1 fold mediating electrostatic interactions through positive and negative faces. Detailed structural analysis revealed additional hydrophobic and polar determinants and started unveiling an ARF/IAA interaction code. Structural progress also shed new light on the DNA binding mode of ARFs showing how they dimerize to bind repeated DNA elements. Here, we discuss the in vitro and in vivo significance of these structural properties for the ARF family of TFs and identify some critical missing information on how specificity might be achieved in the auxin signalling pathway. PMID- 26994658 TI - The Impacts of Droughts in Tropical Forests. AB - Tropical forests exchange more carbon dioxide (CO2) with the atmosphere than any other vegetation type and, thus, form a crucial component of the global carbon cycle. However, the impacts of anthropogenic climate change on drought occurrence and intensity could weaken the tropical forest carbon sink, with resulting feedback to future climates. We urgently need a better understanding of the mechanisms and processes involved to predict future responses of tropical forest carbon sequestration to climate change. Recent progress has been made in the study of drought responses at the molecular, cellular, organ, individual, species, community, and landscape levels. Although understanding of the mechanisms is incomplete, the models used to predict drought impacts could be significantly improved by incorporating existing knowledge. PMID- 26994659 TI - The effect of noise exposure during the developmental period on the function of the auditory system. AB - Recently, there has been growing evidence that development and maturation of the auditory system depends substantially on the afferent activity supplying inputs to the developing centers. In cases when this activity is altered during early ontogeny as a consequence of, e.g., an unnatural acoustic environment or acoustic trauma, the structure and function of the auditory system may be severely affected. Pathological alterations may be found in populations of ribbon synapses of the inner hair cells, in the structure and function of neuronal circuits, or in auditory driven behavioral and psychophysical performance. Three characteristics of the developmental impairment are of key importance: first, they often persist to adulthood, permanently influencing the quality of life of the subject; second, their manifestations are different and sometimes even contradictory to the impairments induced by noise trauma in adulthood; third, they may be 'hidden' and difficult to diagnose by standard audiometric procedures used in clinical practice. This paper reviews the effects of early interventions to the auditory system, in particular, of sound exposure during ontogeny. We summarize the results of recent morphological, electrophysiological, and behavioral experiments, discuss the putative mechanisms and hypotheses, and draw possible consequences for human neonatal medicine and noise health. PMID- 26994660 TI - Auditory steady-state responses in cochlear implant users: Effect of modulation frequency and stimulation artifacts. AB - Previous studies have shown that objective measures based on stimulation with low rate pulse trains fail to predict the threshold levels of cochlear implant (CI) users for high-rate pulse trains, as used in clinical devices. Electrically evoked auditory steady-state responses (EASSRs) can be elicited by modulated high rate pulse trains, and can potentially be used to objectively determine threshold levels of CI users. The responsiveness of the auditory pathway of profoundly hearing-impaired CI users to modulation frequencies is, however, not known. In the present study we investigated the responsiveness of the auditory pathway of CI users to a monopolar 500 pulses per second (pps) pulse train modulated between 1 and 100 Hz. EASSRs to forty-three modulation frequencies, elicited at the subject's maximum comfort level, were recorded by means of electroencephalography. Stimulation artifacts were removed by a linear interpolation between a pre- and post-stimulus sample (i.e., blanking). The phase delay across modulation frequencies was used to differentiate between the neural response and a possible residual stimulation artifact after blanking. Stimulation artifacts were longer than the inter-pulse interval of the 500pps pulse train for recording electrodes ipsilateral to the CI. As a result the stimulation artifacts could not be removed by artifact removal on the bases of linear interpolation for recording electrodes ipsilateral to the CI. However, artifact-free responses could be obtained in all subjects from recording electrodes contralateral to the CI, when subject specific reference electrodes (Cz or Fpz) were used. EASSRs to modulation frequencies within the 30-50 Hz range resulted in significant responses in all subjects. Only a small number of significant responses could be obtained, during a measurement period of 5 min, that originate from the brain stem (i.e., modulation frequencies in the 80-100 Hz range). This reduced synchronized activity of brain stem responses in long-term severely-hearing impaired CI users could be an attribute of processes associated with long-term hearing impairment and/or electrical stimulation. PMID- 26994661 TI - Design, fabrication, and in vitro testing of novel three-dimensionally printed tympanic membrane grafts. AB - The tympanic membrane (TM) is an exquisite structure that captures and transmits sound from the environment to the ossicular chain of the middle ear. The creation of TM grafts by multi-material three-dimensional (3D) printing may overcome limitations of current graft materials, e.g. temporalis muscle fascia, used for surgical reconstruction of the TM. TM graft scaffolds with either 8 or 16 circumferential and radial filament arrangements were fabricated by 3D printing of polydimethylsiloxane (PDMS), flex-polyactic acid (PLA) and polycaprolactone (PCL) materials followed by uniform infilling with a fibrin-collagen composite hydrogel. Digital opto-electronic holography (DOEH) and laser Doppler vibrometry (LDV) were used to measure acoustic properties including surface motions and velocity of TM grafts in response to sound. Mechanical properties were determined using dynamic mechanical analysis (DMA). Results were compared to fresh cadaveric human TMs and cadaveric temporalis fascia. Similar to the human TM, TM grafts exhibit simple surface motion patterns at lower frequencies (400 Hz), with a limited number of displacement maxima. At higher frequencies (>1000 Hz), their displacement patterns are highly organized with multiple areas of maximal displacement separated by regions of minimal displacement. By contrast, temporalis fascia exhibited asymmetric and less regular holographic patterns. Velocity across frequency sweeps (0.2-10 kHz) measured by LDV demonstrated consistent results for 3D printed grafts, while velocity for human fascia varied greatly between specimens. TM composite grafts of different scaffold print materials and varied filament count (8 or 16) displayed minimal, but measurable differences in DOEH and LDV at tested frequencies. TM graft mechanical load increased with higher filament count and is resilient over time, which differs from temporalis fascia, which loses over 70% of its load bearing properties during mechanical testing. This study demonstrates the design, fabrication and preliminary in vitro acoustic and mechanical evaluation of 3D printed TM grafts. Data illustrate the feasibility of creating TM grafts with acoustic properties that reflect sound induced motion patterns of the human TM; furthermore, 3D printed grafts have mechanical properties that demonstrate increased resistance to deformation compared to temporalis fascia. PMID- 26994662 TI - The relative responsiveness of test instruments can be estimated using a meta analytic approach: an illustration with treatments for depression. AB - OBJECTIVES: We present a meta-analytic method that combines information on treatment effects from different instruments from a network of randomized trials to estimate instrument relative responsiveness. STUDY DESIGN AND SETTING: Five depression-test instruments [Beck Depression Inventory (BDI I/II), Patient Health Questionnaire (PHQ9), Hamilton Rating for Depression 17 and 24 items, Montgomery Asberg Depression Rating] and three generic quality of life measures [EuroQoL (EQ 5D), SF36 mental component summary (SF36 MCS), and physical component summary (SF36 PCS)] were compared. Randomized trials of treatments for depression reporting outcomes on any two or more of these instruments were identified. Information on the within-trial ratios of standardized treatment effects was pooled across the studies to estimate relative responsiveness. RESULTS: The between-instrument ratios of standardized treatment effects vary across trials, with a coefficient of variation of 13% (95% credible interval: 6%, 25%). There were important differences between the depression measures, with PHQ9 being the most responsive instrument and BDI the least. Responsiveness of the EQ-5D and SF36 PCS was poor. SF36 MCS performed similarly to depression instruments. CONCLUSION: Information on relative responsiveness of several test instruments can be pooled across networks of trials reporting at least two outcomes, allowing comparison and ranking of test instruments that may never have been compared directly. PMID- 26994663 TI - The anaphase-promoting complex works together with the SCF complex for proteolysis of the S-phase cyclin Clb6 during the transition from G1 to S phase. AB - In Saccharomyces cerevisiae, the S-phase cyclin Clb6 is expressed shortly before the G1/S transition. It has been shown that in S phase the SCF(Cdc4) ubiquitin ligase controls Clb6 proteolysis, which requires cyclin-dependent kinases activity. A Clb6-3A mutant, bearing non-phosphorylatable mutations at S6A, T39A, and S147A, was observed to be hyperstabilized in S-phase but was unstable in mitosis. In this study, we found that the APC(Cdh1) form of the Anaphase Promoting Complex (APC) was required for Clb6 proteolysis in both early and late G1. An in vitro ubiquitination assay confirmed that Clb6 is a substrate for APC(Cdh1). A KEN box and a destruction box in the Clb6N-terminus were identified. Mutations in the KEN box (mkb) and/or the destruction box (mdb) enhanced Clb6 stability in G1. Expression of Clb6mkd, bearing both mutations in the mkb and mdb, allowed cells to bypass the late G1 arrest caused by cdc4-1. This bypass phenotype was observed to depend upon CDK phosphorylation at residues S6, T39 and S147. Compared to Clb6, overexpression of Clb6ST, bearing all five mutations of S6A, T39A, S147A, mkb and mdb in combination, had a greater effect on promoting expression of Clb2 and S-phase entry, caused a greater G2 delay and a greater defect in cell division. Swe1 was also required for bud emergence when Clb6ST was overexpressed. Our observations suggest that both APC(Cdh1) and SCF(Cdc4) dependent proteolysis of Clb6 at the G1/S border are crucial for multiple cell cycle regulated events including proper expression of Clb2, the G1/S and G2/M cell cycle transitions and for proper completion of cell division at mitotic exit. PMID- 26994664 TI - Facegram - Objective quantitative analysis in facial reconstructive surgery. AB - Evaluation of effectiveness in reconstructive plastic surgery has become an increasingly important asset in comparing and choosing the most suitable medical procedure to handle facial disfigurement. Unfortunately, traditional methods to assess the results of surgical interventions are mostly qualitative and lack information about movement dynamics. Along with this, the few existing methodologies tailored to objectively quantify surgery results are not practical in the medical field due to constraints in terms of cost, complexity and poor suitability to clinical environment. These limitations enforce an urgent need for the creation of a new system to quantify facial movement and allow for an easy interpretation by medical experts. With this in mind, we present here a novel method capable of quantitatively and objectively assess complex facial movements, using a set of morphological, static and dynamic measurements. For this purpose, RGB-D cameras are used to acquire both color and depth images, and a modified block matching algorithm, combining depth and color information, was developed to track the position of anatomical landmarks of interest. The algorithms are integrated into a user-friendly graphical interface and the analysis outcomes are organized into an innovative medical tool, named facegram. This system was developed in close collaboration with plastic surgeons and the methods were validated using control subjects and patients with facial paralysis. The system was shown to provide useful and detailed quantitative information (static and dynamic) making it an appropriate solution for objective quantitative characterization of facial movement in a clinical environment. PMID- 26994665 TI - The six-year outcome of alcohol use disorders in men: A population based study from India. AB - BACKGROUND: Despite the large and growing public health problem of alcohol use disorders (AUD) in India there is a dearth of evidence about the longitudinal outcomes in AUD. The aim of this study is to describe the course and outcomes of AUD in a population based sample of men in India. METHODS: A community cohort of 1899 adult (18-49 years at baseline) men who participated in a cross-sectional survey in Goa, India between 2006 and 08, were re-interviewed face to face 6 years later (2012-14). A range of outcomes including social problems (e.g., workplace problems, domestic violence), morbidity (e.g., range of physical and mental health problems), biological parameters (e.g., mean corpuscular volume [MCV], gamma-glutamyl transpeptidase [GGT]) and mortality were measured at follow up. For the association of AUD at baseline with outcomes at follow-up, multivariable logistic regression was used to estimate odds ratios (OR). Analyses were weighted to account for baseline sampling design, age distribution, rural and urban sample sizes, number of adults aged 18-49 years in the household (at baseline), and non-response (at baseline). RESULTS: 1514 (79.7%) were seen at follow-up; a loss to follow up of 20.3%. At follow up, 3.7% of baseline non drinkers and 15.0% of baseline casual drinkers had AUD. 46.9% of baseline hazardous drinkers and 55.4% baseline harmful drinkers continued to have AUD at follow up. Of those with AUD at baseline, 21.8% had stopped drinking at follow up. Compared to being abstinent, harmful drinking at baseline was associated with several outcomes at follow-up: workplace/social problems, hypertension, death, tobacco use, suicidality, anxiety disorders, and raised GGT (p<0.002). Hazardous drinking at baseline was associated with tobacco use and raised GGT and MCV (p<0.002) at follow-up. CONCLUSION: Our findings of high persistent and new AUD in the community and the association with a range of long term adverse events are an important addition to the limited evidence about the course and outcomes of AUD in India, which have the potential for informing health policy. PMID- 26994666 TI - The forensic analysis of office paper using oxygen isotope ratio mass spectrometry. Part 1: Understanding the background population and homogeneity of paper for the comparison and discrimination of samples. AB - Isotope ratio mass spectrometry (IRMS) using carbon isotopes has previously been shown to be a robust and discriminating technique for the comparison of document papers. This study aims to examine the inter and intra sample variability for oxygen isotopes measured in standard 80gsm white document papers, to inform the comparison of document papers in forensic casework. 123 paper samples collected from Australia and New Zealand over a 24-month period were measured for their bulk oxygen isotopic abundance and were found to sit within a range of 150/00. A homogeneity study was undertaken which included examining the variability of samples at the sheet, ream and brand source levels. The results of this study were used to construct guidelines for sample comparison and as such, 95% confidence intervals were observed to be inappropriate for use given the high intra sample variability. Instead, a 1.40/00 discrimination range (0.70/00 either side of the measured value) was defined for use as a benchmark for discrimination when samples were measured in the same sequence. Utilising this value, 82% of the samples could be discriminated using a paired comparison, demonstrating a strong potential for use within forensic casework. PMID- 26994667 TI - Comment on "Mathematical modeling of unicellular microalgae and cyanobacteria metabolism for biofuel production" by Baroukh et al. [Curr Opin Biotechnol. 2015, 33:198-205]. PMID- 26994668 TI - Cloning and analysis of gene expression of interleukin-17 homolog in triangle shell pearl mussel, Hyriopsis cumingii, during pearl sac formation. AB - Successful allograft of mantle tissues in certain bivalve mollusks can form pearl sacs secreting nacre for pearl production. Little was known, however, about the immune consequences in response to the tissue transplantation. In the present study, interleukin (IL)-17, one of the key regulatory genes of alloimmunity, was cloned from the triangle-shell pearl mussel (HcIL-17) Hyriopsis cumingii by high throughput sequencing of the mantle transcriptome. The sequence of HcIL-17 contains an open reading frame of 567 bp encoding a putative protein of 188 amino acid residues. Analysis of sequence characteristics, multiple sequence alignment and phylogenetic analysis indicated HcIL-17 was a novel member in the mollusk IL 17 family. Expression of the HcIL-17 gene in donor mantle tissues and in hemocytes of recipient mussel was up-regulated dramatically within 7 days in response to the mantle tissue allograft for pearl aquaculture, suggesting remarkable proinflammatory responses during pearl sac formation in triangle-shell pearl mussels. Analysis of the time-course expression of HcIL-17 gene revealed the induction of HcIL-17 was time-dependent, reflecting the different periods of alloimmune events in triangle-shell mussels. The results of this study provide essential background information for further investigation of mollusk alloimmunity. PMID- 26994669 TI - Protective oral vaccination against infectious salmon anaemia virus in Salmo salar. AB - Infectious salmon anemia (ISA) is a systemic disease caused by an orthomyxovirus, which has a significant economic impact on the production of Atlantic salmon (Salmo salar). Currently, there are several commercial ISA vaccines available, however, those products are applied through injection, causing stress in the fish and leaving them susceptible to infectious diseases due to the injection process and associated handling. In this study, we evaluated an oral vaccine against ISA containing a recombinant viral hemagglutinin-esterase and a fusion protein as antigens. Our findings indicated that oral vaccination is able to protect Atlantic salmon against challenge with a high-virulence Chilean isolate. The oral vaccination was also correlated with the induction of IgM-specific antibodies. On the other hand, the vaccine was unable to modulate expression of the antiviral related gene Mx, showing the importance of the humoral response to the disease survival. This study provides new insights into fish protection and immune response induced by an oral vaccine against ISA, but also promises future development of preventive solutions or validation of the current existing therapies. PMID- 26994670 TI - A beta-integrin from sea cucumber Apostichopus japonicus exhibits LPS binding activity and negatively regulates coelomocyte apoptosis. AB - Integrins are a family of membrane glycoproteins, which are the major receptors for extracellular matrix and cell-cell adhesion molecules. In this study, a 1038 bp sequence representing the full-length cDNA of a novel beta-integrin subunit (designated as AjITGB) was cloned from Apostichopus japonicas by using combined transcriptome sequencing and RACE approaches. The deduced amino acid sequence of AjITGB shared a conserved tripeptide Arg-Gly-Asp (RGD) binding domain with an S diglyceridecysteine or N-Palm cysteine residue (C(31)), a transmembrane domain, and a beta-integrin cytoplasmic domain. Spatial distribution analysis showed that AjITGB was constitutively expressed in all tested tissues with dominant expression in the muscles and weak expression in the respiratory tree. The pathogen Vibrio splendidus challenge and LPS stimulation could both significantly down-regulate the mRNA expression of AjITGB. Functional investigation revealed that recombinant AjITGB displayed higher LPS binding activity but lower binding activity to PGN and MAN. More importantly, knockdown of AjITGB by specific siRNA resulted in the significant promotion of coelomocyte apoptosis in vitro. Results indicated that AjITGB may serve as an apoptosis inhibitor with LPS binding activity during host-pathogen interaction in sea cucumber. PMID- 26994671 TI - What's new in fish cytokine research? PMID- 26994672 TI - Identification of the Bcl-2 family protein gene BOK from orange-spotted grouper (Epinephelus coioides) involved in SGIV infection. AB - Apoptosis plays vital roles in many physiological process and immune response. BOK is one of the central regulators in apoptosis. In this study, a new BOK homolog (Ec-BOK) was cloned and characterized from Orange-spotted grouper, Epinephelus coioides. Ec-BOK encoded a 210 amino acid peptides which shared 97% identity to Stegastes partitus BOK protein, contained four BH domains and one transmembrane region. Ec-BOK widely expressed in all analyzed tissues with the higher expressions in kidney and spleen. Its expression level was up-regulated after SGIV infection in vitro. Further analysis revealed that overexpression of Ec-BOK inhibited viral genes transcriptions and virus replication in fish cell. Our findings suggested that Ec-BOK might play a role in the immune response against virus. PMID- 26994673 TI - Immunotoxicological effects of cadmium on Labeo rohita, with emphasis on the expression of HSP genes. AB - The present study evaluated the effects of exposure (28 days) to a sub-lethal concentration of cadmium (Cd) (0.65 mg CdCl2 L(-1)) on the immune responses and expression of immune-related and heat shock protein (HSP) genes in Labeo rohita, an important aquacultured fish species. Among the immune parameters studied, significantly lower lysozyme activity was observed in fish 28 days post-exposure (dpe) to Cd as compared to control fish. Alternative complement pathway activity was slightly higher in the Cd-exposed group at 2 dpe than in controls, and this activity declined gradually thereafter. The phagocytic activity and serum immunoglobulin M (IgM) levels were insignificantly lower in the Cd-exposed group at all assessed time points than in controls. Among serum enzymatic activities, peroxidase activity was always higher in the Cd-exposed group than in controls, but the increase was insignificant at all assessed time points. Additionally, serum glutamic-pyruvic transaminase and alkaline phosphatase activities were significantly higher in the Cd-exposed group at 14 and 28 dpe. Immune and HSP gene expression patterns were observed in kidney and liver tissues, respectively, by RT-PCR, and HSPs were further analysed by immunoblotting. Cd had an immunosuppressive effect, leading to down-regulation of TNF-alpha, IL-1beta, IL 10, and IFN-gamma. However, Cd exposure led to the up-regulation of HSP47, HSP60, HSP70, HSP78, and HSP90, indicating Cd-induced cellular stress. Taken together, the results of this study demonstrate the immunotoxic effect of Cd. Cd exposure makes Labeo rohita immunocompromised, and this could subsequently increase the disease susceptibility of Labeo rohita. PMID- 26994674 TI - Effects of relationship context on contraceptive use among young women. AB - OBJECTIVES: To understand how relationship status influences contraceptive use among young people. STUDY DESIGN: Data were collected as part of a longitudinal study on hormonal contraception among unmarried adolescent and young women who wanted to avoid pregnancy for at least one year, recruited at family planning clinics in the San Francisco Bay Area. Follow-up surveys were completed at 3, 6, and 12months. Longitudinal analysis was used to examine whether relationship characteristics, including type and length of sexual relationship are associated with current use of effective contraception. RESULTS: Among women with a partner at baseline, 78%, 70%, and 61% had the same partner at 3, 6, and 12months follow up, respectively. Women in casual relationships were less likely to use effective contraceptive methods, compared to women in consistent relationships (AOR=0.67, p<.01). Women in new relationships (0-3months) were less likely to use effective contraceptive methods (AOR=0.60, p<.001) compared to women in relationships more than one year in length. Younger women (AOR=0.76, p<.05), black women (AOR=0.67, p<.05) and Latina women (AOR=0.73, p<.05) were also significantly less likely to use effective contraception. These effects remained even after controlling for condom use. CONCLUSIONS: Relationship type and length are independently significantly associated with current effective contraceptive use among adolescent and young women. Women in casual relationships and new relationships were significantly less likely to use effective contraceptive methods. IMPLICATIONS: Family planning providers should discuss women's relationship context and association with contraceptive use in order to help women think of contraception as a long-term personal strategy. Since relationship status affects contraceptive use, providers and programs that aim to reduce unintended pregnancy can consider strategies to create a paradigm shift around contraceptive use that focuses on the woman's reproductive goals, current life stage, and life goals. PMID- 26994675 TI - A Two-Stage Protocol With Vacuum Sealing Drainage for the Treatment of Type C Pilon Fractures. AB - Management of type C pilon fractures remains controversial and challenging. The aim of the present study was to provide a 2-stage protocol with vacuum sealing drainage for the treatment of type C pilon fractures. From March 2009 to March 2012, 16 patients (mean age 42.3 years) were admitted to our department with type C pilon fractures and treated with single-stage external fixation and second stage internal fixation (anteromedial incision) combined with vacuum sealing drainage. The American Orthopaedic Foot and Ankle Society scale score averaged 86.5 for this group of patients. The range of motion was 30 degrees +/- 8.9 degrees . An excellent or good American Orthopaedic Foot and Ankle Society scale score was obtained for all patients. None of the 16 patients developed skin necrosis, nonunion, or fixation failure during the follow-up period. Moreover, the visual analog scale pain scores were 0.7 +/- 0.8, 0.9 +/- 0.7, and 1.4 +/- 1.0 during rest, active movement, and weightbearing, respectively. The postoperative radiographs showed excellent treatment effects. A 2-stage protocol, combined with vacuum sealing drainage, for the treatment of type C pilon fractures can eliminate deep infection and complex surgery and is a simple and effective treatment method. In addition, full exposure of the anteromedial incision, the avoidance of the anterior tibial muscle tendon sheath, and the avoidance of soft tissue injuries are generally recommended in this operation. PMID- 26994676 TI - A comparative evaluation of the translucency of zirconias and lithium disilicate for monolithic restorations. AB - STATEMENT OF PROBLEM: Studies comparing the translucency of zirconias and lithium disilicates are limited. PURPOSE: The purpose of this in vitro study was to measure the translucency of recently developed translucent zirconias and compare them with lithium disilicate. MATERIAL AND METHODS: Five types of zirconia, Prettau Anterior (Zirkonzahn GmbH), BruxZir (Glidewell Laboratories), Katana HT, Katana ST, and Katana UT (Kurary Noritake Dental Inc), and 1 type of lithium disilicate, e.max CAD LT (Ivoclar Vivadent AG), were assessed. Non-colored zirconia test specimens (n=5) were prepared as rectangles with dimensions of 15*10*0.5 and 15*10*1.0 mm. The shade of lithium disilicate was B1. A spectrophotometer (Evolution 300 UV-Vis) with an integrating sphere was used to evaluate the total transmittance of light as a percentage (Tt%) at a wavelength of 555 nm for comparison among groups. The Welch robust test for equality of means was used to compare group means (alpha=.025) and post hoc pairwise comparisons among groups were performed with the Dunnett T3 method. RESULTS: For the 0.5 mm thickness groups, the Tt% was 31.90 +/-0.49 for Prettau Anterior, 28.82 +/-0.22 for BruxZir, 28.49 +/-0.14 for Katana HT, 31.67 +/-0.24 for Katana ST, 33.73 +/-0.13 for Katana UT, and 40.32 +/-0.25 for e-max CAD LT. Post hoc tests indicated that all groups were significantly different from each other, except for between BruxZir and Katana HT, and between Prettau Anterior and Katana ST. Katana UT was significantly more translucent than all other zirconias, and e max CAD LT was significantly more translucent than all zirconias. For the 1.0 mm thickness groups, the Tt% was 22.58 +/-0.41 for Prettau Anterior, 20.13 +/-0.22 for BruxZir, 20.18 +/-0.39 for Katana HT, 21.86 +/-0.39 for Katana ST, 23.37 +/ 0.27 for Katana UT, and 27.05 +/-0.56 for e-max CAD LT. Post hoc tests indicated that all materials were significantly different from each other, except for between BruxZir and Katana HT, and among Prettau Anterior, Katana ST and Katana UT which were significantly more translucent than all other zirconias and less translucent than e-max CAD LT. CONCLUSION: At a thickness of 0.5 mm, Katana UT was significantly more translucent than all other zirconias, and e-max CAD LT was significantly more translucent than all zirconias. At a thickness of 1.0 mm, Prettau Anterior, Katana ST, and Katana UT were significantly more translucent than all other zirconias and less than e-max CAD LT. PMID- 26994677 TI - Are physicians able to recognition ineffective (agonal) breathing as element of cardiac arrest? PMID- 26994678 TI - Knowledge, attitude, and practices of paramedics regarding optic nerve sheath diameter ultrasonography. PMID- 26994679 TI - Tracheal ultrasonography and ultrasonographic lung sliding for confirming endotracheal tube placement: Speed and Reliability. AB - BACKGROUND: In this study we aimed to evaluate the success of ultrasonography (USG) for confirming the tube placement and timeliness by tracheal USG and ultrasonographic lung sliding in resuscitation and rapid sequence intubation. MATERIALS AND METHODS: This study was a prospective, single-center, observational study conducted in the emergency department of a tertiary care hospital. Patients were prospectively enrolled in the study. Patients who went under emergency intubation because of respiratory failure, cardiac arrest or severe trauma included in the study. Patients with severe neck trauma, neck tumors, history of neck operation or tracheotomy and under 18years old were excluded from the study. RESULTS: A total of 115 patients included in the study. The mean age was 67.2+/ 17.1 with age 16-95years old. Among 115 patients 30 were cardiac arrest patients other 85 patients were non-cardiac arrest patients intubated with rapid sequence intubation. The overall accuracy of the ultrasonography was 97.18% (95% CI, 90.19 99.66%), and the value of kappa was 0.869 (95% CI, 0.77-0.96), indicating a high degree of agreement between the ultrasonography and capnography. The ulrasonography took significantly less time than capnography in total. DISCUSSION: Ultrasonography achieved high sensitivity and specificity for confirming tube placement and results faster than end-tidal carbon dioxide. Ultrasonography is a good alternative for confirming the endotracheal tube placement. Future studies should examine the use of ultrasonography as a method for real-time assessment of endotracheal tube placement by emergency physicians with only basic ultrasonographic training. PMID- 26994680 TI - Which intravascular access method to choose during cardiopulmonary resuscitation? PMID- 26994682 TI - Variability in management of hematologic malignancy patients with venous thromboembolism and chemotherapy-induced thrombocytopenia. PMID- 26994681 TI - Early neurologic examination is not reliable for prognostication in post-cardiac arrest patients who undergo therapeutic hypothermia. AB - BACKGROUND: Recent advances in post-cardiac arrest (CA) care including therapeutic hypothermia (TH) have improved survival and favorable neurologic outcomes for survivors of CA. Survivors often present with deep coma and lack of brainstem reflexes, which are generally associated with adverse outcomes in many disease processes. Little is known regarding the role of initial emergency department (ED) neurological examination and its potential for prognostication. OBJECTIVES: The purpose of this study is to determine if components of a standardized neurologic examination are reliable prognosticators in patients recently resuscitated from CA. We hypothesize that lack of neurologic function does not reliably predict an adverse outcome and, therefore, should not be used to determine eligibility for TH. METHODS: A standardized neurologic examination was performed in the ED on a prospective, convenience cohort of post-CA patients presenting to a CA resuscitation center who would undergo a comprehensive postarrest care pathway that included TH. Data such as prior sedation or active neuromuscular blockade were documented to evaluate for the presence of possible confounders. Examination findings were then compared with hospital survival and neurologic outcome at discharge as defined by the cerebral performance category (CPC) score as documented in the institutional TH registry. RESULTS: Forty-nine subjects were enrolled, most of whom presented comatose with a Glasgow Coma Scale of 3 (n=41, 83.7%). Nineteen subjects (38.8%) had absence of all examination findings, of which 4 of 19 (21.1%) survived to hospital discharge. Of those with at least 1 positive examination finding, 13 of 30 subjects (43.3%) survived to hospital discharge. Subgroup analysis showed that 9 of the 19 patients with absence of brainstem reflexes did not have evidence of active neuromuscular blockade at the time of the examination; 2 of 9 (22.1%) survived to hospital discharge. Eight of these subjects in this group had not received any prior sedation; 1 of 8 (12.5%) survived to hospital discharge. Only 1 of the 17 subjects who survived was discharged with poor neurologic function with a CPC score=3, whereas all others who survived had good neurologic function, CPC score=1. CONCLUSION: In this cohort of patients treated in a comprehensive postarrest care pathway that included TH, absence of neurologic function on initial ED presentation was not reliable for prognostication. Given these findings, clinicians should refrain from using the initial ED neurological examination to guide the aggressiveness of care or in counseling of family members regarding anticipated outcome. PMID- 26994683 TI - Human cord blood endothelial progenitors promote post-ischemic angiogenesis in immunocompetent mouse model. AB - BACKGROUND: Human cord blood (CB) endothelial colony forming cells (ECFCs) are endowed with high vascular regenerative ability in immunodeficient mice, but their immunogenicity and susceptibility to rejection in immunocompetent models has yet to be explored. METHODS: We injected CB ECFCs in non-immuno-suppressed C57BL/6J mice after having induced the hindlimb ischemia and we investigated their contribution to the recovery from the ischemic injury. Human ECFCs (hECFCs) were administered by intramuscular injection and hindlimb blood perfusion was measured by laser Doppler analysis at 7-day intervals for 28days after treatment. Mice were sacrificed after 7 and 28days and immunohistochemistry for specific human (CD31) and mouse (von Willebrand factor) endothelial antigens was carried out. Before euthanasia, blood samples to assess cytokines and angiogenic growth factor levels were collected. RESULTS: Mice injected with hECFCs showed a prompter and greater recovery of blood flow than controls. Several endothelial cells of human origin were detected at day7 after injection and their number declined progressively. Likewise, a progressive increase of mouse-derived vascular structures were observed, paralleled by the amplified endogenous production of various soluble mediators of angiogenesis, including Vascular Endothelial Growth Factor and Fibroblast Growth Factor. CONCLUSIONS: Overall, our findings are consistent with the hypothesis that human ECFCs might expand the endogenous vascular repair potential of recipients and support their possible HLA independent unconventional use. PMID- 26994684 TI - Differential Expression of microRNAs in Urinary Extracellular Vesicles Obtained From Hypertensive Patients. PMID- 26994686 TI - A Nephrology Fellows' Communication Skills Course: An Educational Quality Improvement Report. AB - BACKGROUND: Nephrology fellows need expertise navigating challenging conversations with patients throughout the course of advanced kidney disease. However, evidence shows that nephrologists receive inadequate training in this area. This study assessed the effectiveness of an educational quality improvement intervention designed to enhance fellows' communication with patients who have advanced kidney disease. STUDY DESIGN: Quality improvement project. SETTING & PARTICIPANTS: Full-day annual workshops (2013-2014) using didactics, discussion, and practice with simulated patients. Content focused on delivering bad news, acknowledging emotion, discussing care goals in dialysis decision making when prognosis is uncertain, and addressing dialysis therapy withdrawal and end of life. Participants were first-year nephrology fellows from 2 Harvard-affiliated training programs (N=26). QUALITY IMPROVEMENT PLAN: Study assessed the effectiveness of an intervention designed to enhance fellows' communication skills. OUTCOMES: Primary outcomes were changes in self-reported patient communication skills, attitudes, and behaviors related to discussing disease progression, prognostic uncertainty, dialysis therapy withdrawal, treatments not indicated, and end of life; responding to emotion; eliciting patient goals and values; and incorporating patient goals into recommendations. MEASUREMENTS: Surveys measured prior training, pre- and postcourse perceived changes in skills and values, and reported longer term (3-month) changes in communication behaviors, using both closed- and open-ended items. RESULTS: Response rates were 100% (pre- and postsurveys) and 68% (follow-up). Participants reported improvement in all domains, with an overall mean increase of 1.1 (summed average scores: precourse, 2.8; postcourse, 3.9 [1-5 scale; 5 = "extremely well prepared"]; P<0.001), with improvement sustained at 3 months. Participants reported meaningful changes integrating into practice specific skills taught, such as "Ask-Tell-Ask" and using open-ended questions. LIMITATIONS: Self-reported data may overestimate actual changes; small sample size and the programs' affiliation with a single medical school may limit generalizability. CONCLUSIONS: A day-long course addressing nephrology fellows' communication competencies across the full course of patients' illness experience can enhance fellows' self reported skills and practices. PMID- 26994685 TI - Changes in Kidney Function After Transjugular Intrahepatic Portosystemic Shunts Versus Large-Volume Paracentesis in Cirrhosis: A Matched Cohort Analysis. AB - BACKGROUND: Patients with cirrhosis and refractory ascites have physiologic and hormonal dysregulation that contributes to decreased kidney function. Placement of a transjugular intrahepatic portosystemic shunt (TIPS) can reverse these changes and potentially improve kidney function. We sought to evaluate change in estimated glomerular filtration rate (eGFR) following TIPS placement. STUDY DESIGN: Retrospective, matched cohort analysis. SETTINGS & PARTICIPANTS: Patients who underwent first-time TIPS placement for refractory ascites in 1995 to 2014. Frequency matching was used to generate a comparator group of patients with cirrhosis and ascites treated with serial large-volume paracentesis (LVP) in a 1:1 fashion. PREDICTOR: TIPS placement compared to serial LVP. OUTCOME: Change in eGFR over 90 days' follow-up. MEASUREMENTS: Multivariable regression stratified by baseline eGFR<60 versus >=60mL/min/1.73m(2); analysis of effect modification between TIPS placement and baseline eGFR. RESULTS: 276 participants (TIPS, n=138; serial LVP, n=138) were analyzed. After 90 days, eGFRs increased significantly after TIPS placement in participants with baseline eGFRs<60mL/min/1.73m(2) compared to treatment with serial LVP (21 [95% CI, 13-29] mL/min/1.73m(2); P<0.001) and was no different in those with eGFRs>=60mL/min/1.73m(2) (1 [95% CI, 9 to 12] mL/min/1.73m(2); P=0.8). There was significant effect modification between TIPS status and baseline eGFR (P=0.001) in a model that included all participants. LIMITATIONS: Outcomes restricted by clinically recorded data; clinically important differences may still exist between the TIPS and LVP cohorts despite good statistical matching. CONCLUSIONS: TIPS placement was associated with significant improvement in kidney function. This was most prominent in participants with baseline eGFRs<60mL/min/1.73m(2). Prospective studies of TIPS use in populations with eGFRs<60mL/min/1.73m(2) are needed to evaluate these findings. PMID- 26994687 TI - Laparoscopic Renal Denervation for Uncontrolled Hypertension Due to Medication Intolerance: A Case Report. AB - Resistant hypertension is challenging to treat, and most patients with the condition fail to achieve blood pressure control, putting them at increased risk for adverse long-term outcomes. We present the case of a 59-year-old woman with resistant hypertension due to intolerance to nearly all antihypertensive medications. After failure to achieve blood pressure control over a 5-year period, with blood pressures as high as 220/110mmHg, the patient underwent surgical treatment with bilateral laparoscopic renal denervation. Immediately after the procedure, as well as at the 1-, 3-, 9-, and 12-month follow-ups, the patient's blood pressure was reduced to the range of 120-140/80-90mmHg. PMID- 26994688 TI - Emergence of triple-subtype reassortants of fatal human H5N6 avian influenza virus in Yunnan, China. PMID- 26994689 TI - When proglottids and scoleces conflict: phylogenetic relationships and a family level classification of the Lecanicephalidea (Platyhelminthes: Cestoda). AB - This study presents the first comprehensive phylogenetic analysis of the interrelationships of the morphologically diverse elasmobranch-hosted tapeworm order Lecanicephalidea, based on molecular sequence data. With almost half of current generic diversity having been erected or resurrected within the last decade, an apparent conflict between scolex morphology and proglottid anatomy has hampered the assignment of many of these genera to families. Maximum likelihood and Bayesian analyses of two nuclear markers (D1-D3 of lsrDNA and complete ssrDNA) and two mitochondrial markers (partial rrnL and partial cox1) for 61 lecanicephalidean species representing 22 of the 25 valid genera were conducted; new sequence data were generated for 43 species and 11 genera, including three undescribed genera. The monophyly of the order was confirmed in all but the analyses based on cox1 data alone. Sesquipedalapex placed among species of Anteropora and was thus synonymized with the latter genus. Based on analyses of the concatenated dataset, eight major groups emerged which are herein formally recognised at the familial level. Existing family names (i.e., Lecanicephalidae, Polypocephalidae, Tetragonocephalidae, and Cephalobothriidae) are maintained for four of the eight clades, and new families are proposed for the remaining four groups (Aberrapecidae n. fam., Eniochobothriidae n. fam., Paraberrapecidae n. fam., and Zanobatocestidae n. fam.). The four new families and the Tetragonocephalidae are monogeneric, while the Cephalobothriidae, Lecanicephalidae and Polypocephalidae comprise seven, eight and four genera, respectively. As a result of their unusual morphologies, the three genera not included here (i.e., Corrugatocephalum, Healyum and Quadcuspibothrium) are considered incertae sedis within the order until their familial affinities can be examined in more detail. All eight families are newly circumscribed based on morphological features and a key to the families is provided. Aspects of morphological evolution and host associations are discussed in a phylogenetic context for each family and for the order as a whole. Lecanicephalidean genera lacking apical structures were confirmed as the earliest diverging lineages. Proglottid anatomy was determined to be much more conserved and indicative of phylogenetic affinities than scolex morphology. Collectively, the Lecanicephalidea parasitize three of the four orders of Batoidea-their almost exclusive absence from skates (Order Rajiformes) appears to be real; only a few records from sharks exist. At the family level, the breadth of host associations is correlated with taxonomic diversity of the family. The degree to which factors such as intermediate host use or host specificity at any stage in the life-cycle shape these patterns is currently unknown. PMID- 26994690 TI - Synthesis and biological evaluation of pyrrolo[2,3-b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA. AB - A series of thirty two novel pyrrolo[2,3-b]pyridine analogues synthesized, characterized ((1)H NMR, (13)C NMR and MS) and cytotoxic evaluation of these molecules carried out over a panel of three human cancer cell lines including A549 (lung cancer), HeLa (cervical cancer) and MDA MB-231 (breast cancer), using sulforhodamine B assay method. Few molecules such as 5c, 5d, 5e, 5h, 5k, 5m, 5n, 5q, 5r, 7f, 7j, 7g and 7k exhibited maximum growth inhibitory action against the tested cancer cell lines at lower micro molar concentration. Noticeably, compounds exhibited good growth inhibition in all three cancer cell lines in the range of 0.12 MUM-9.84 MUM. Further study exposed that one of the active compound 5d could efficiently intercalate into calf thymus DNA to form 5d-DNA complex which might block DNA replication to influence their antiproliferative activity. The molecular interactions of all the synthesized analogs were also supported by molecular docking simulations. We believe that further optimization of these compounds will lead to potential anticancer agents. PMID- 26994691 TI - Synthesis and biological evaluation of novel 2,3-dihydrochromeno[3,4-d]imidazol 4(1H)-one derivatives as potent anticancer cell proliferation and migration agents. AB - In this study, a series of novel molecules containing chromeno [3,4-d] imidazol 4(1H)-one was synthesized and their biological activities were evaluated. Among them, compound 35 showed a dramatic anticancer activity against HCT116 and MCF-7, and the flow cytometry assays demonstrated that it could arrest G0/G1 cell-cycle and induce apoptosis of SW620 cells in a dose-dependent manner. Besides, it also blocked MCF-7 cancer cell migration. Moreover, it inhibited tumor growth in HCT116 subcutaneously implanted xenografted mice. Taken together, compound 35 may be a promising candidate for anti-cancer agent as well as metastatic one. PMID- 26994692 TI - Copper complexes based on chiral Schiff-base ligands: DNA/BSA binding ability, DNA cleavage activity, cytotoxicity and mechanism of apoptosis. AB - Four copper(II) complexes with chiral Schiff-base ligands, [Cu(R-L(1))2].EtOAc (1) and [Cu(S-L(1))2].EtOAc (2), [Cu(R-L(2))2].EtOAc (3) and [Cu(S-L(2))2].EtOAc (4), (R/S-HL(1) = (R/S)-(1-naththyl)-salicylaldimine, R/S-HL(2) = (R/S)-(1 naththyl)-3-methoxysalicylaldimine, EtOAc = ethyl acetate) were synthesized to serve as artificial nucleases and anticancer drugs. All complexes and R/S-HL(1) ligands were structurally characterized by X-ray crystallography. The interaction of these complexes with CT-DNA was researched via several spectroscopy methods, which indicates that complexes bind to CT-DNA by moderate intercalation binding mode. Moreover, DNA cleavage experiments revealed that the complexes exhibited remarkable DNA cleavage activities in the presence of H2O2via the generation of hydroxyl radical. Particularly, complex 4 also could nick DNA with the production of (1)O2. And all complexes exhibited excellent cytotoxicity to MDA-MB-231, A549 and Hela human cancer cells in micromole magnitude. Furthermore, complex 4 exhibited comparable cytotoxic effect to cisplatin against the proliferation of MDA-MB-231 and A549 cancer cells, as well as showed better anticancer ability to the three cancer cells than the other complexes. The results of cell cycle analysis indicated that complexes 3-4 could induce G2/M phase cell cycle arrest. Furthermore, MDA-MB-231 cells treated with 3 and 4 were subjected to apoptosis and death by generation of ROS and the activation of caspase-3. Interestingly, the chiral complexes 3 and 4 may induce cell apoptosis through extrinsic and mitochondrial intrinsic pathway, respectively. PMID- 26994693 TI - An integrated overview on pyrrolizines as potential anti-inflammatory, analgesic and antipyretic agents. AB - Despite the existence of huge number of NSAIDs, the quest for safer drugs is still in the focus of several drug discovery programs. Pyrrolizine heterocyclic system is among the privileged scaffolds utilized in this regard. At least one of these pyrrolizines, ketorolac, has reached the market. The current review represents a collective effort to highlight the reported pyrrolizines with anti inflammatory and analgesic potential and categorize them into eight different classes. Furthermore, the various synthetic approaches, structure-activity relationship as well as metabolic pathways have been discussed. Taken together, this review sets a base for researchers to design and synthesize novel pyrrolizine-based libraries for further development into safer and efficient anti inflammatory and analgesic agents. PMID- 26994694 TI - Detection of Merkel cell polyomavirus and human papillomavirus DNA in porocarcinoma. AB - BACKGROUND: Increasing evidences support the role of Merkel cell polyomavirus (MCPyV) and human papillomavirus (HPV) in non-cutaneous and cutaneous tumours. Porocarcinoma is a rare malignant neoplasm that arises from the intraepidermal ductal portion of the eccrine sweat glands. The aetiology of porocarcinoma is largely unknown and no systematic studies have been done to investigate the implication of infectious agents in the pathogenesis of this tumour. OBJECTIVES: To investigate the possible association between MCPyV and/or HPV infection and porocarcinoma. STUDY DESIGN: Forty-four formalin-fixed paraffin-embedded (FFPE) porocarcinomas (40 primary and 4 metastatic) and 10 healthy skin specimens (controls), were analysed for the presence of MCPyV and HPV DNA using molecular detection methods. RESULTS: MCPyV DNA was found in 27/40 (68%) primary porocarcinomas and in 3/10 (30%) controls (Fisher exact test: p<0.04). No significant difference in viral load was observed between tumours and healthy skin. Moreover, 2/40 primary porocarcinomas tested positive for high-risk HPV16. Cutaneous beta-HPV infection was detected in 16/40 (40%) porocarcinomas and in 6/10 (60%) controls. No particular beta-HPV types were significantly associated with tumour or with healthy skin. Two out of 4 metastatic biopsies were MCPyV DNA positive. All metastatic samples had mixed infections with cutaneous HPV types. CONCLUSIONS: This study demonstrated a significantly high prevalence of MCPyV and the presence of a broad spectrum of HPV types in porocarcinoma and provided the first available data about viral infections in this tumour. To understand the role, if any, of viral infections in the pathogenesis of porocarcinoma further studies are needed. PMID- 26994695 TI - Prevention of cervical cancer: journey to develop the first human papillomavirus virus-like particle vaccine and the next generation vaccine. AB - In 2006, the first human papillomavirus (HPV) virus-like particle (VLP) vaccine was licensed. Gardasil((r)), the quadrivalent HPV 6, 11, 16 and 18 recombinant VLP vaccine (4vHPV), developed by Merck demonstrated remarkable efficacy in prevention of important clinical pre-cursors to cervical cancer and genital warts. The vaccine was designed to protect against HPV 16 and 18 that cause ~70% of cervical cancers and HPV 6 and 11 that cause ~90% of genital warts. Initially, Gardasil((r)) was indicated in the United States for women 9-26 years of age for the prevention of HPV 16 and 18-related cervical, vulvar and vaginal cancer, HPV 6, 11, 16 and 18-related genital intraepithelial neoplasia and the prevention of HPV 6 and 11-related genital warts. Subsequently, a bivalent HPV 16 and 18 VLP vaccine, Cervarix (2vHPV) developed by GlaxoSmithKline was licensed. Since the original licensures, the indications for Gardasil((r)) have been expanded to include males and a vaccine with extended HPV coverage, Gardasil 9 (9vHPV), licensed in 2014. PMID- 26994696 TI - The effects of organic fouling on the removal of radionuclides by reverse osmosis membranes. AB - The removals of cesium (Cs) and strontium (Sr), two hazardous and abundant radionuclides in aquatic environment, were assessed with their isotopes in a synthetic water containing Suwannee River natural organic matter (SRNOM), a natural surface water (SW) and a wastewater effluent (WW) by two different types of ultra-low pressure RO membranes (M1 and M2). The rejections of Sr by the membranes M1 and M2 were higher than 97.5% and 96.0%, respectively, and the rejections of Cs exceeded 90.0% and 85.0%, respectively, in the filtration of real water. The membrane M1 exhibited a more significant flux decline in the filtration of the SRNOM solution, while more severe flux declines were observed with the membrane M2 in the filtration of SW and WW. Protein-like materials with relatively high molecular weight were the main contributors to the flux decline, and humic-acid-like compounds had little effect on the flux decline. Donnan exclusion and size exclusion by humic-acid-like compounds improved the rejections by the membrane M2 with weaker hydrophilicity, while the cake-enhanced concentration polarization reduced the rejections of Cs and Sr by the membrane M1 with stronger hydrophilicity. The ionic strength in the real water resulted in the mitigation of membrane fouling. This study provided important insights into foulant characterization and the mechanisms of organic-fouling-enhanced rejections of Cr and Sr by ultra-low pressure RO membranes. PMID- 26994697 TI - Simultaneous determination of organotin pesticides by HPLC-ICP-MS and their sorption, desorption, and transformation in freshwater sediments. AB - In order to better assess their environmental risks, the sorption and degradation of triphenyltin hydroxide, azocyclotin and fenbutatin oxide were studied in two sediments under varying laboratory conditions in this study. An analytical method for simultaneous determination of the three organotins in environmental samples was firstly developed using high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). The limit of detection and limit of quantification for standards ranged from 0.13 to 1.46 MUg/L. Fortification study showed that when spiked at 2-250 MUg/kg the mass recoveries were 73.7 119.6%. Sorption isotherm experiments indicated that the organotins could be strongly adsorbed by the sediments, and organotin sorption kinetics obeyed the pseudo second-order kinetic model. The sorption affinity was inversely related to their water solubility. All isotherms fitted with the Henry mode fairly well (r(2) > 0.96) with distribution coefficients (Kd) ranging from 746.1 to 2465.2 mL/g. The three organotins could rapidly move from the upper water layer to the lower sediment layer, and they were all of moderate degradation compounds with the degradation half lives varying from 38.3 to 84.5d in anaerobic and aerobic water-sediment systems. The degradation rate seemed to be positively related to organic matter content of sediment. Result inferred that the three organotins had the low risks to pollute groundwater when applied on dry land and could moderately degrade in water-sediment system. However, more attention should still be paid to these organotins due to the wide application on agricultural field. PMID- 26994698 TI - Overexpression of heat shock factor 1 maintains TAR DNA binding protein 43 solubility via induction of inducible heat shock protein 70 in cultured cells. AB - TAR DNA binding protein 43 (TDP-43) is a nuclear protein that has been shown to have altered homeostasis in the form of neuronal nuclear and cytoplasmic aggregates in some familial and almost all cases of sporadic amyotrophic lateral sclerosis as well as 51% of frontotemporal lobar degeneration and 57% of Alzheimer's disease cases. Heat shock proteins (HSPs), such as HSP70, recognize misfolded or aggregated proteins and refold, disaggregate, or turn them over and are upregulated by the master transcription factor heat shock factor 1 (HSF1). Here, we explore the effect of HSF1 overexpression on proteotoxic stress-related alterations in TDP-43 solubility, proteolytic processing, and cytotoxicity. HSF1 overexpression reduced TDP-43-positive puncta concomitantly with upregulating HSP70 and HSP90 protein levels. HSF1 overexpression or pharmacological activation sustained TDP-43 solubility and significantly reduced truncation of TDP-43 in response to inhibition of the proteasome with Z-Leu-Leu-Leu-al, and this was reversed by HSF1 inhibition. HSF1 activation conferred protection against toxicity associated with TDP-43 C-terminal fragments without globally increasing the activity of the ubiquitin proteasome system (UPS) while concomitantly reducing the induction of autophagy, suggesting that HSF1 protection is an early event. In support of this, inhibition of HSP70 ATPase activity further reduced TDP-43 solubility. HSF1 knockout significantly increased TDP-43 insolubility and accelerated TDP-43 fragmentation in response to proteotoxic stress. Overall, this study shows that HSF1 overexpression protects against TDP-43 pathology by upregulation of chaperones, especially HSP70, rather than enhancing autophagy or the UPS during times of proteotoxic stress. (c) 2016 Wiley Periodicals, Inc. PMID- 26994700 TI - Detection of Abeta Monomers and Oligomers: Early Diagnosis of Alzheimer's Disease. AB - Alzheimer's disease (AD), as the most common progressive neurodegenerative disorder, is pathologically characterized by deposition of extracellular plaque composed of amyloid-beta peptide (Abeta). Different assembled states of Abeta have been considered as both important biomarkers and drug targets for the diagnosis and therapy of AD. Recent studies demonstrate that small, diffusible Abeta oligomers formed by aggregation of Abeta monomers are the major toxic agents in AD. Therefore, the development of reliable assays for Abeta (both monomers and oligomers) will be important for the early differential diagnosis of dementia, predicting the progression of AD, as well as monitoring the effectiveness of novel anti-Abeta drugs for AD. In this review, we summarize the recent progress made in the development of techniques for detection of Abeta monomers and oligomers. In particular, the principles governing the design of these sensors are classified and summarized. Moreover, the advantages and disadvantages of the assays are evaluated. This review also discusses the improvements and challenges for application of these assays in the early diagnosis of AD. PMID- 26994701 TI - Department of Corrections. PMID- 26994702 TI - Is the Fate of the ACA Settled or Not? PMID- 26994703 TI - Shelter in the Storm: Health Care Systems and Climate Change. PMID- 26994704 TI - Attention 2016 Health Policy Shoppers: Read the Fine Print. PMID- 26994705 TI - Global Health Security After Ebola: Four Global Commissions. PMID- 26994706 TI - Rethinking Science and Politics. PMID- 26994707 TI - Robotic Surgery: An Example of When Newer Is Not Always Better but Clearly More Expensive. PMID- 26994708 TI - Injurious Inequalities. PMID- 26994709 TI - Knowledge of and Attitudes Toward Evidence-Based Guidelines for and Against Clinical Preventive Services: Results from a National Survey. AB - POLICY POINTS: Both the underuse and overuse of clinical preventive services relative to evidence-based guidelines are a public health concern. Informed consumers are an important foundation of many components of the Affordable Care Act, including coverage mandates for proven clinical preventive services recommended by the US Preventive Services Task Force. Across sociodemographic groups, however, knowledge of and positive attitudes toward evidence-based guidelines for preventive care are extremely low. Given the demonstrated low levels of consumers' knowledge of and trust in guidelines, coupled with their strong preference for involvement in preventive care decisions, better education and decision-making support for evidence-based preventive services are greatly needed. CONTEXT: Both the underuse and overuse of clinical preventive services are a serious public health problem. The goal of our study was to produce population-based national data that could assist in the design of communication strategies to increase knowledge of and positive attitudes toward evidence-based guidelines for clinical preventive services (including the US Preventive Services Task Force, USPSTF) and to reduce uncertainty among patients when guidelines change or are controversial. METHODS: In late 2013 we implemented an Internet based survey of a nationally representative sample of 2,529 adults via KnowledgePanel, a probability-based survey panel of approximately 60,000 adults, statistically representative of the US noninstitutionalized population. African Americans, Hispanics, and those with less than a high school education were oversampled. We then conducted descriptive statistics and multivariable logistic regression analysis to identify the prevalence of and sociodemographic characteristics associated with key knowledge and attitudinal variables. FINDINGS: While 36.4% of adults reported knowing that the Affordable Care Act requires insurance companies to cover proven preventive services without cost sharing, only 7.7% had heard of the USPSTF. Approximately 1 in 3 (32.6%) reported trusting that a government task force would make fair guidelines for preventive services, and 38.2% believed that the government uses guidelines to ration health care. Most of the respondents endorsed the notion that research/scientific evidence and expert medical opinion are important for the creation of guidelines and that clinicians should follow guidelines based on evidence. But when presented with patient vignettes in which a physician made a guideline-based recommendation against a cancer-screening test, less than 10% believed that this recommendation alone, without further dialogue and/or the patient's own research, was sufficient to make such a decision. CONCLUSIONS: Given these demonstrated low levels of knowledge and mistrust regarding guidelines, coupled with a strong preference for shared decision making, better consumer education and decision supports for evidence-based guidelines for clinical preventive services are greatly needed. PMID- 26994710 TI - Differing Strategies to Meet Information-Sharing Needs: Publicly Supported Community Health Information Exchanges Versus Health Systems' Enterprise Health Information Exchanges. AB - POLICY POINTS: Community health information exchanges have the characteristics of a public good, and they support population health initiatives at the state and national levels. However, current policy equally incentivizes health systems to create their own information exchanges covering more narrowly defined populations. Noninteroperable electronic health records and vendors' expensive custom interfaces are hindering health information exchanges. Moreover, vendors are imposing the costs of interoperability on health systems and community health information exchanges. Health systems are creating networks of targeted physicians and facilities by funding connections to their own enterprise health information exchanges. These private networks may change referral patterns and foster more integration with outpatient providers. CONTEXT: The United States has invested billions of dollars to encourage the adoption of and implement the information technologies necessary for health information exchange (HIE), enabling providers to efficiently and effectively share patient information with other providers. Health care providers now have multiple options for obtaining and sharing patient information. Community HIEs facilitate information sharing for a broad group of providers within a region. Enterprise HIEs are operated by health systems and share information among affiliated hospitals and providers. We sought to identify why hospitals and health systems choose either to participate in community HIEs or to establish enterprise HIEs. METHODS: We conducted semistructured interviews with 40 policymakers, community and enterprise HIE leaders, and health care executives from 19 different organizations. Our qualitative analysis used a general inductive and comparative approach to identify factors influencing participation in, and the success of, each approach to HIE. FINDINGS: Enterprise HIEs support health systems' strategic goals through the control of an information technology network consisting of desired trading partners. Community HIEs support obtaining patient information from the broadest set of providers, but with more dispersed benefits to all participants, the community, and patients. Although not an either/or decision, community and enterprise HIEs compete for finite organizational resources like time, skilled staff, and money. Both approaches face challenges due to vendor costs and less than-interoperable technology. CONCLUSIONS: Both community and enterprise HIEs support aggregating clinical data and following patients across settings. Although they can be complementary, community and enterprise HIEs nonetheless compete for providers' attention and organizational resources. Health policymakers might try to encourage the type of widespread information exchange pursued by community HIEs, but the business case for enterprise HIEs clearly is stronger. The sustainability of a community HIE, potentially a public good, may necessitate ongoing public funding and supportive regulation. PMID- 26994711 TI - Strategic Planning in Population Health and Public Health Practice: A Call to Action for Higher Education. AB - POLICY POINTS: Scarce resources, especially in population health and public health practice, underlie the importance of strategic planning. Public health agencies' current planning and priority setting efforts are often narrow, at times opaque, and focused on single metrics such as cost-effectiveness. As demonstrated by SMART Vaccines, a decision support software system developed by the Institute of Medicine and the National Academy of Engineering, new approaches to strategic planning allow the formal incorporation of multiple stakeholder views and multicriteria decision making that surpass even those sophisticated cost-effectiveness analyses widely recommended and used for public health planning. Institutions of higher education can and should respond by building on modern strategic planning tools as they teach their students how to improve population health and public health practice. CONTEXT: Strategic planning in population health and public health practice often uses single indicators of success or, when using multiple indicators, provides no mechanism for coherently combining the assessments. Cost-effectiveness analysis, the most complex strategic planning tool commonly applied in public health, uses only a single metric to evaluate programmatic choices, even though other factors often influence actual decisions. METHODS: Our work employed a multicriteria systems analysis approach--specifically, multiattribute utility theory--to assist in strategic planning and priority setting in a particular area of health care (vaccines), thereby moving beyond the traditional cost-effectiveness analysis approach. FINDINGS: (1) Multicriteria systems analysis provides more flexibility, transparency, and clarity in decision support for public health issues compared with cost-effectiveness analysis. (2) More sophisticated systems-level analyses will become increasingly important to public health as disease burdens increase and the resources to deal with them become scarcer. CONCLUSIONS: The teaching of strategic planning in public health must be expanded in order to fill a void in the profession's planning capabilities. Public health training should actively incorporate model building, promote the interactive use of software tools, and explore planning approaches that transcend restrictive assumptions of cost effectiveness analysis. The Strategic Multi-Attribute Ranking Tool for Vaccines (SMART Vaccines), which was recently developed by the Institute of Medicine and the National Academy of Engineering to help prioritize new vaccine development, is a working example of systems analysis as a basis for decision support. PMID- 26994712 TI - Evidence and the Politics of Deimplementation: The Rise and Decline of the "Counseling and Testing" Paradigm for HIV Prevention at the US Centers for Disease Control and Prevention. AB - POLICY POINTS: In situations of scientific uncertainty, public health interventions, such as counseling for HIV infection, sometimes must be implemented before obtaining evidence of efficacy. The history of HIV counseling and testing, which served as the cornerstone of HIV prevention efforts at the US Centers for Disease Control and Prevention (CDC) for a quarter of a century, illustrates the influence of institutional resistance on public health decision making and the challenge of de-implementing well-established programs. CONTEXT: In 1985, amid uncertainty about the accuracy of the new test for HIV, public health officials at the Centers for Disease Control and Prevention (CDC) and AIDS activists agreed that counseling should always be provided both before and after testing to ensure that patients were tested voluntarily and understood the meaning of their results. As the "exceptionalist" perspective that framed HIV in the early years began to recede, the purpose of HIV test counseling shifted over the next 30 years from emphasizing consent, to providing information, to encouraging behavioral change. With this increasing emphasis on prevention, HIV test counseling faced mounting doubts about whether it "worked." The CDC finally discontinued its preferred test counseling approach in October 2014. METHODS: Drawing on key informant interviews with current and former CDC officials, behavioral scientists, AIDS activists, and others, along with archival material, news reports, and scientific and governmental publications, we examined the origins, development, and decline of the CDC's "counseling and testing" paradigm for HIV prevention. FINDINGS: Disagreements within the CDC emerged by the 1990s over whether test counseling could be justified on the basis of efficacy and cost. Resistance to the prospect of policy change by supporters of test counseling in the CDC, gay activists for whom counseling carried important ethical and symbolic meanings, and community organizations dependent on federal funding made it difficult for the CDC to de-implement the practice. CONCLUSIONS: Analyses of changes in public health policy that emphasize the impact of research evidence produced in experimental or epidemiological inquiries may overlook key social and political factors involving resistance to deimplementation that powerfully shape the relationship between science and policy. PMID- 26994715 TI - Meta-analysis of negative-pressure wound therapy for closed surgical incisions. AB - BACKGROUND: Postoperative wound complications are common following surgical procedures. Negative-pressure wound therapy (NPWT) is well recognized for the management of open wounds and has been applied recently to closed surgical incisions. The evidence base to support this intervention is limited. The aim of this study was to assess whether NPWT reduces postoperative wound complications when applied to closed surgical incisions. METHODS: This was a systematic review and meta-analysis of randomized clinical trials of NPWT compared with standard postoperative dressings on closed surgical incisions. RESULTS: Ten studies met the inclusion criteria, reporting on 1311 incisions in 1089 patients. NPWT was associated with a significant reduction in wound infection (relative risk (RR) 0.54, 95 per cent c.i. 0.33 to 0.89) and seroma formation (RR 0.48, 0.27 to 0.84) compared with standard care. The reduction in wound dehiscence was not significant. The numbers needed to treat were three (seroma), 17 (dehiscence) and 25 (infection). Methodological heterogeneity across studies led to downgrading of the quality of evidence to moderate for infection and seroma, and low for dehiscence. CONCLUSION: Compared with standard postoperative dressings, NPWT significantly reduced the rate of wound infection and seroma when applied to closed surgical wounds. Heterogeneity between the included studies means that no general recommendations can be made yet. PMID- 26994718 TI - Snapshot Quiz 15/11. PMID- 26994716 TI - Influence of body composition profile on outcomes following colorectal cancer surgery. AB - BACKGROUND: Muscle depletion is characterized by reduced muscle mass (myopenia), and increased infiltration by intermuscular and intramuscular fat (myosteatosis). This study examined the role of particular body composition profiles as prognostic markers for patients with colorectal cancer undergoing curative resection. METHODS: Patients with colorectal cancer undergoing elective surgical resection between 2006 and 2011 were included. Lumbar skeletal muscle index (LSMI), visceral adipose tissue (VAT) surface area and mean muscle attenuation (MA) were calculated by analysis of CT images. Reduced LSMI (myopenia), increased VAT (visceral obesity) and low MA (myosteatosis) were identified using predefined sex-specific skeletal muscle index values. Univariable and multivariable Cox regression models were used to determine the role of different body composition profiles on outcomes. RESULTS: Some 805 patients were identified, with a median follow-up of 47 (i.q.r. 24.9-65.6) months. Multivariable analysis identified myopenia as an independent prognostic factor for disease-free survival (hazard ratio (HR) 1.53, 95 per cent c.i. 1.06 to 2.39; P = 0.041) and overall survival (HR 1.70, 1.25 to 2.31; P < 0.001). The presence of myosteatosis was associated with prolonged primary hospital stay (P = 0.034), and myopenic obesity was related to higher 30-day morbidity (P = 0.019) and mortality (P < 0.001) rates. CONCLUSION: Myopenia may have an independent prognostic effect on cancer survival for patients with colorectal cancer. Muscle depletion may represent a modifiable risk factor in patients with colorectal cancer and needs to be targeted as a relevant endpoint of health recommendations. PMID- 26994713 TI - Community-Academic Partnerships: A Systematic Review of the State of the Literature and Recommendations for Future Research. AB - POLICY POINTS: Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research, to provide firsthand knowledge and insight. Based on our systematic review of major literature databases, we recommend using a single term, community-academic partnership (CAP), and a conceptual definition to unite multiple research disciplines and strengthen the field. Interpersonal and operational factors that facilitate or hinder the collaborative process have been consistently identified, including "trust among partners" and "respect among partners" (facilitating interpersonal factors) and "excessive time commitment" (hindering operational factor). Once CAP processes and characteristics are better understood, the effectiveness of collaborative partner involvement can be tested. CONTEXT: Communities, funding agencies, and institutions are increasingly involving community stakeholders as partners in research. Community stakeholders can provide firsthand knowledge and insight, thereby increasing research relevance and feasibility. Despite the greater emphasis and use of community-academic partnerships (CAP) across multiple disciplines, definitions of partnerships and methodologies vary greatly, and no systematic reviews consolidating this literature have been published. The purpose of this article, then, is to facilitate the continued growth of this field by examining the characteristics of CAPs and the current state of the science, identifying the facilitating and hindering influences on the collaborative process, and developing a common term and conceptual definition for use across disciplines. METHODS: Our systematic search of 6 major literature databases generated 1,332 unique articles, 50 of which met our criteria for inclusion and provided data on 54 unique CAPs. We then analyzed studies to describe CAP characteristics and to identify the terms and methods used, as well as the common influences on the CAP process and distal outcomes. FINDINGS: CAP research spans disciplines, involves a variety of community stakeholders, and focuses on a large range of study topics. CAP research articles, however, rarely report characteristics such as membership numbers or duration. Most studies involved case studies using qualitative methods to collect data on the collaborative process. Although various terms were used to describe collaborative partnerships, few studies provided conceptual definitions. Twenty-three facilitating and hindering factors influencing the CAP collaboration process emerged from the literature. Outcomes from the CAPs most often included developing or refining tangible products. CONCLUSIONS: Based on our systematic review, we recommend using a single term, community-academic partnership, as well as a conceptual definition to unite multiple research disciplines. In addition, CAP characteristics and methods should be reported more systematically to advance the field (eg, to develop CAP evaluation tools). We have identified the most common influences that facilitate and hinder CAPs, which in turn should guide their development and sustainment. PMID- 26994720 TI - Preface: Perspectives on Creativity Development. PMID- 26994721 TI - Creativity Doesn't Develop in a Vacuum. AB - The skills, knowledge, attitudes, motivations, and personality traits that lead to creative thinking and creative behavior do not exist-and do not develop-in a vacuum. They are inextricably tied to content, to domains, in particular, and they therefore vary by domains. The more we learn about creativity, the more we discover how domain specific creativity is. This means we cannot nurture creativity, or any of the skills or attributes that contribute to creativity, without thinking about content. One cannot become physically fit by doing just one kind of exercise that trains a single set of muscles; all-around fitness requires diverse exercises that use and train many different sets of muscles. So it is with creativity. Different domains require different creativity-relevant skills, knowledge, attitudes, motivations, and personality traits. If we want to help children and adolescents become more creative, then we need to attend to the domains we use in the development of creativity. PMID- 26994722 TI - Pretend Play: Antecedent of Adult Creativity. AB - This article reviews the theoretical and empirical literature in the area of pretend play as a predictor of adult creativity. There is strong evidence that processes expressed in pretend play are associated with measures of creativity, especially with divergent thinking. There is some evidence from longitudinal studies that this association is stable over time. Converging evidence suggests that cognitive and affective processes in pretend play are involved in adult creative production. However, there is a lack of consensus in the field as to whether engaging in pretend play actually facilitates creative thinking. In addition, many other variables (opportunity, tolerance for failure, motivation, work ethic, etc.) determine whether children with creative potential are actually creative in adulthood. In spite of the many methodological challenges in conducting research in the play area, it is important to continue investigating specific processes expressed in play and their developmental trajectories. Large samples in multisite studies would be ideal in investigating the ability of specific play processes to predict these creative processes and creative productivity in adulthood. PMID- 26994723 TI - "Peaks, Slumps, and Bumps": Individual Differences in the Development of Creativity in Children and Adolescents. AB - This article reviews developmental studies of creativity in children and adolescents with a focus on "peaks" and "slumps" that have often been described in the literature. The irregularity of the development of creativity is interpreted in light of conceptual and measurement issues and with regard to the interaction between individual-level resources, task-specific demands, and environmental influences, resulting in apparent individual differences in the development of creativity. The need for longitudinal designs, multidimensional and multi-domain assessment of creative potential limiting the contribution of task-specific factors is outlined and discussed as an important direction for developmental research on creativity. PMID- 26994724 TI - The Cross-Cultural Invariance of Creative Cognition: A Case Study of Creative Writing in U.S. and Russian College Students. AB - Unlike intelligence, creativity has rarely been investigated from the standpoint of cross-cultural invariance of the structure of the instruments used to measure it. In the study reported in this article, we investigated the cross-cultural invariance of expert ratings of creative stories written by undergraduate students from the Russian Federation and the United States. Analyses of differential rater and item functioning using Many-Facet Rasch Measurement and multiple levels of invariance using confirmatory factor analyses suggested partial measurement invariance of creative ability estimates obtained using this method in two cultures. Russian and U.S. students demonstrated similar overall levels of creativity; however, U.S. students received higher emotionality ratings than Russian students did. The findings are discussed in the context of viewing creativity as at least a partially culturally invariant trait whose manifestation is moderated by culture-specific semantic knowledge and patterns of linguistic behavior. PMID- 26994725 TI - Inhibitory Control as a Core Process of Creative Problem Solving and Idea Generation from Childhood to Adulthood. AB - Developmental cognitive neuroscience studies tend to show that the prefrontal brain regions (known to be involved in inhibitory control) are activated during the generation of creative ideas. In the present article, we discuss how a dual process model of creativity-much like the ones proposed to account for decision making and reasoning-could broaden our understanding of the processes involved in creative ideas generation. When generating creative ideas, children, adolescents, and adults tend to follow "the path of least resistance" and propose solutions that are built on the most common and accessible knowledge within a specific domain, leading to fixation effect. In line with recent theory of typical cognitive development, we argue that the ability to resist the spontaneous activation of design heuristics, to privilege other types of reasoning, might be critical to generate creative ideas at all ages. In the present review, we demonstrate that inhibitory control at all ages can actually support creativity. Indeed, the ability to think of something truly new and original requires first inhibiting spontaneous solutions that come to mind quickly and unconsciously and then exploring new ideas using a generative type of reasoning. PMID- 26994726 TI - Creativity Development in Adolescence: Insight from Behavior, Brain, and Training Studies. AB - Creativity is a multifaceted construct that recruits different cognitive processes. Here, we summarize studies that show that creativity develops considerably during adolescence with different developmental trajectories for insight, verbal divergent thinking, and visuospatial divergent thinking. Next, these developmental time courses are mapped to changes in brain activity when individuals perform divergent thinking tasks. The findings point to an important role of the prefrontal cortex for generating novelty and complexity. Finally, the potentials and limitations of training creativity in adolescence are described. The findings are interpreted vis-a-vis the dynamic changes that occur during adolescence in brain development and behavioral control processes. PMID- 26994727 TI - Creative Aspirations or Pipe Dreams? Toward Understanding Creative Mortification in Children and Adolescents. AB - What experiences influence the development of creativity in children and adolescents? One experience is the mortification of creative aspirations. Creative mortification (CM) refers to the loss of one's willingness to pursue a particular creative aspiration following a negative performance outcome. The purpose of this article is to introduce an empirically testable model of CM. Specifically, the model highlights how CM can result from interpreting a negative performance outcome through the lens of internal attributions, fixed ability beliefs, and the experience of shame. The model further posits that young people's level of aspirational commitment, the feedback they receive, and their sociocultural context can moderate their interpretations and experiences of negative performance outcomes and CM. PMID- 26994728 TI - Commentary: Overview of Developmental Perspectives on Creativity and the Realization of Potential. AB - The articles in this issue of New Directions for Child and Adolescent Development nicely summarize recent findings about creativity and development. This commentary underscores some of the key ideas and puts them into a larger context (i.e., the corpus of creativity research). It pinpoints areas of agreement (e.g., the need to take both generative and convergent processes into account when examining developmental changes in creative behavior) but balances this with a discussion of concerns. These include (a) problems with the concept of Big C creativity, as it may confound the realization of creative potential, (b) lack of attention given to cultural relativity, and (c) inappropriate testing of divergent thinking. Still, the progress in the research is clear and the fulfillment of creative potentials increasingly likely. PMID- 26994729 TI - Commentary: The Development of Creativity--Ability, Motivation, and Potential. AB - A major question for research on the development of creativity is whether it is interested in creative potential (a prospective approach that uses measures early in life to predict adult creativity) or in children's creativity for its own sake. We suggest that a focus on potential for future creativity diminishes the fascinating creative world of childhood. The contributions to this issue can be organized in light of an ability * motivation framework, which offers a fruitful way for thinking about the many factors that foster and impede creativity. The contributions reflect a renewed interest in the development of creativity and highlight how this area can illuminate broader problems in creativity studies. PMID- 26994731 TI - Influence of Starvation on Respiratory Metabolism and Pyridine Nucleotide Levels in the Marine Dinoflagellate Oxyrrhis marina. AB - Respiratory oxygen consumption rate (RO2) and potential respiration (Phi) has been monitored during a food deprivation period in the heterotrophic dinoflagellate Oxyrrhis marina. Phi was determined by measuring the activity of the enzymes from the electron transport system (ETS), the major contributor to the oxygen consumption in the cells. Additionally, we have quantified for the first time the concentration of pyridine nucleotides in this organism, both in their oxidized (NAD(P)(+)) and reduced forms (NAD(P)H). These molecules are the main electron donors at the beginning of the ETS. We observed a dramatic decrease in RO2 within the first days, whereas Phi steadily, but more gradually declined during the entire experiment. This led to a decrease of the RO2 /Phi with time. The intracellular total pool of NAD and NADP concentration, in turn, dropped exponentially in a manner parallel to the RO2. This strong decrease was mainly driven by a reduction in the concentration of the oxidized forms. The present work constitutes a first step in clarifying the role of intracellular NAD and NADP concentrations and the redox status in the control of in vivo RO2 in marine organisms. PMID- 26994732 TI - Stibinidene and Bismuthinidene as Two-Electron Donors for Transition Metals (Co and Mn). AB - The reaction of stibinidene and bismuthinidene ArM [where Ar=C6 H3 -2,6 (CH=NtBu)2 ; M=Sb (1), Bi (2)] with transition metal (TM) carbonyls Co2 (CO)8 and Mn2 (CO)10 produced unprecedented ionic complexes [(ArM)2 Co(CO)3 ](+) [Co(CO)4 ](-) and [(ArM)2 Mn(CO)4 ](+) [Mn(CO)5 ](-) [where M=Sb (3, 5), Bi (4, 6)]. The pnictinidenes 1 and 2 behaved as two-electron donors in this set of compounds. Besides the M->TM bonds, the topological analysis also revealed a number of secondary interactions contributing to the stabilization of cationic parts of titled complexes. PMID- 26994733 TI - Desmoplastic nested spindle cell tumours and nested stromal epithelial tumours of the liver. AB - Desmoplastic nested spindle cell tumour of liver (DNSTL), nested stromal epithelial tumour (NSET) and calcifying nested stromal-epithelial tumour (CNSET) are recently described entities with similar morphology, immunohistochemistry and molecular genetics. These are rare entities with only three large case series described till date. These tumours commonly present in the paediatric age group. NSETs, in addition have been described to be associated with ectopic adrenocorticotropic hormone (ACTH) production and Cushingoid features. It is important to discuss this rare group of tumours with a low malignant potential as the most common radiological differential diagnosis is hepatoblastoma, which has a relatively poorer prognosis. Thus, a pathologist needs to keep this entity in mind, so as to offer a correct histological diagnosis. PMID- 26994734 TI - Planning for Ancillary Care Provision: Lessons From the Developing World. AB - As part of a study designed to assess a new strategy for increasing health research participation by members of underrepresented populations in the United States, we explored expectations about volunteering for research among people from lower income and largely minority communities in Madison, Wisconsin. Members of these communities often saw research participation as a means to access health care that might otherwise be unavailable to them. In light of persistent structural barriers to access, and the resulting health disparities, we argue that one cannot assume the existence of a "fair exchange" in which a community is likely to benefit from the results of research conducted with members of that community. We use ethical analysis and empirical research conducted in the developing world to explore how investigators in the United States might think about their obligations to provide ancillary care. PMID- 26994735 TI - A Case-Study of the Resources and Functioning of Two Research Ethics Committees in Western India. AB - Assessing the resources and functioning of research ethics committees (RECs) in low-resource settings poses many challenges. We conducted a case study of two medical college RECs (A and B) in Western India utilizing the Research Ethics Committee Quality Assurance Self-Assessment Tool (RECQASAT) as well as in-depth interviews with representative members to evaluate REC effectiveness. REC A and B obtained 62% and 67% of allowable points on the RECQASAT. These scores together with findings from the in-depth interviews suggest the need for significant improvement in REC effectiveness particularly in the areas of membership and educational training, organizational aspects, recording minutes, communicating decisions, and REC resources. Developing evidence-based best practices and strengthening infrastructure are essential to enhancing REC efficacy in low resource countries. PMID- 26994736 TI - Topological DNA Assemblies Containing Identical or Fraternal Twins. AB - DNA catenanes are assemblies made up of two or more DNA rings linked together through mechanical bonds, and they are desirable for engineering unique nanoscale devices. However, current methods of synthesizing DNA catenanes rely on the formation of strong linking duplexes between component units to enable interlocking and thus do not permit the synthesis of complex single-stranded DNA structures with freely functioning units. We have recently reported DNA sequences that can thread through a DNA circle without the formation of a linking duplex. Here we show that these unique DNA molecules can be further used to make intricate symmetric or asymmetric DNA [3]catenanes, single-stranded DNA assemblies made up of a central mother ring interlocked to two identical or fraternal twin daughter rings, which have never been reported before. These addressable freely functioning interlocked DNA rings should facilitate the design of elaborate nanoscale machines based on DNA. PMID- 26994737 TI - From lab to clinic: Extinction of cued cravings to reduce overeating. AB - Food cue reactivity is a strong motivation to eat, even in the absence of hunger. Therefore, food cue reactivity might sabotage healthy eating, induce weight gain and impede weight loss or weight maintenance. Food cue reactivity can be learned via Pavlovian appetitive conditioning: It is easily acquired but the extinction of appetitive responding seems to be more challenging. Several properties of extinction make it fragile: extinction does not erase the original learning and extinction is context-dependent. These properties threaten full extinction and increase the risk of full relapse. Extinction procedures are discussed to reduce or prevent the occurrence of rapid reacquisition, spontaneous recovery, renewal and reinstatement after extinction. A translation to food cue exposure treatment is made and suggestions are provided, such as conducting the exposure in relevant contexts, using occasional reinforcement and targeting expectancy violation instead of habituation. A new hypothesis proposed here is that the adding of inhibition training to strengthen inhibition skills that reduce instrumental responding, might be beneficial to improve food cue exposure effects. PMID- 26994738 TI - Family meals and eating practices among mothers in Santos, Brazil: A population based study. AB - This study investigates family meals among mothers and explores associations between eating with family and sociodemographic characteristics, body mass index, and eating practices. A population-based cross-sectional study, using complex cluster-sampling, was conducted in the city of Santos, Brazil with 439 mothers. Frequency of family meals was assessed by asking if mothers did or did not usually have a) breakfast, b) lunch, and c) dinner with family. Linear regression analyses were conducted for the number of meals eaten with family per day and each of the potential explanatory variables, adjusting for the mother's age. Poisson regression with robust variance was used to analyze each factor associated with eating with family as classified categorically: a) sharing meals with family, b) not eating any meals with family. Only 16.4% (n = 72) of participants did not eat any meals with family. From the 83.6% (n = 367) of mothers that had at least one family meal per day, 69.70% (n = 306) ate dinner with their families. Mothers aged >=40 years reported significantly fewer meals eaten with family compared to mothers aged 30-39 years (beta: -0.26, p = 0.04). Having family meals was 54% more prevalent among mothers with >=12 years of education (PR for no meals eaten with family: 0.54, 95% CI: 0.30; 0.96, p = 0.03), when compared to mothers with less than nine years of education. Eating no meals with family was 85% more prevalent among mothers who reported that eating was one of the biggest pleasures in their lives (PR: 1.85, 95% CI: 1.21; 2.82, p = 0.004). We suggest the need for further research investigating the effects of family meals on mothers' health through nutritional and phenomenological approaches. PMID- 26994739 TI - The Healthy Meal Index: A tool for measuring the healthfulness of meals served to children. AB - Family meals have been associated with higher diet quality and reduced risk of obesity in children. Observational studies of the family meal have been employed with increasing frequency, yet there is currently no tool available for measuring the healthfulness of food served during the meal. Here we present the development and validation of the Healthy Meal Index (HMI), a novel tool for scoring the healthfulness of foods served to children during a meal, as well as sociodemographic predictors of meal scores. Parents of 233 children, aged 4-8 years, self-recorded three home dinners. A research assistant obtained a list of foods available during the meal (meal report) via phone call on the night of each video-recorded meal. This meal report was coded into component food groups. Subsequently, meals were scored based on the availability of more healthy "Adequacy foods" and the absence of "Moderation foods", (of which reduced consumption is recommended, according to pediatric dietary guidelines). Adjusted linear regression tested the association of sociodemographic characteristics with HMI scores. A validation study was conducted in a separate sample of 133 children with detailed meal data. In adjusted models, female children had higher HMI Moderation scores (p = 0.02), but did not differ in HMI Adequacy or Total scores. Parents with more education served meals with higher HMI Adequacy (p = 0.001) and Total scores (p = 0.001), though no significant difference was seen in HMI Moderation score (p = 0.21). The validation study demonstrated that the HMI was highly correlated with servings of foods and nutrients estimated from observations conducted by research staff. The HMI is a valuable tool for measuring the quality of meals served to children. PMID- 26994740 TI - Regularity and beyond: Impaired production and comprehension of inflectional morphology in semantic dementia. AB - Studies on inflectional morphology in semantic dementia (SD) have focused on the contrast between the regular and the irregular English past-tense. These studies aimed to contrast the claims of single- and dual-mechanism theories. However, both theories can account for impaired production of irregular verbs observed in SD. According to the dual-mechanism theory, this impairment is related to word retrieval difficulties, while according to single-mechanism theory it is the consequence of semantic impairment. However, authors suggest that it is time to envision a broader role for semantic memory in the production of semantically encoded aspects of inflectional morphology. This study reports the performance of 10 French-speaking patients with SD in three tasks of inflectional morphology. Their performances were compared to those of a group of 20 age-, gender- and education-matched adults without cognitive impairment. Results show that SD patients had difficulties producing tense and person inflection in verbs and pseudo-verbs, whether regular or pseudo-regular. In a second task in which participants were directly exposed to regularity manipulations, SD patients tended to choose a more typical or predictable alternative over a correctly inflected verb. Results of the third task show that their difficulties in producing semantically encoded aspects of inflection, such as tense, are related to difficulties to understand the semantic content conveyed by inflectional morphemes. Overall, these results support the claim that semantic impairment can cause morphological deficits that do not only affect irregular verbs, but that also have impacts on the production and comprehension of semantic information conveyed by inflectional morphemes. PMID- 26994741 TI - Cross-modal comparisons of stimulus specificity and commonality in phonological processing. AB - Phonological processing is a fundamental ability which underlies language comprehension. Functional neuroanatomy of phonology constitutes a matter of ongoing debate. In the present study, subjects performed visual (rhyme detection) and auditory (identification of spoken words starting with a given consonant) tasks that were contrasted with matched nonverbal tasks. We identified regions critical for phonological processing which were either stimulus specific or supramodal. The results revealed a high degree of modality specificity in both visual and auditory networks. Moreover, we observed a modality independent region in the left middle temporal gyrus (MTG)/superior temporal sulcus (STS), between a more anterior temporal area with auditory specificity and a more posterior temporal area with visual specificity. This dissociation in functional neuroanatomy suggests that this area may be a core region for supramodal phonological processing, acting as a gateway between spatially separate, but stimulus specific, phonological processes and more general linguistic functions. PMID- 26994742 TI - Recent developments in biological water oxidation. AB - Rapid progress has been made in the last five years towards resolution of the structure of nature's water splitting catalyst - a Mn4O5Ca cofactor embedded in Photosystem II - especially in the field of X-ray crystallography. In addition, recent magnetic resonance data have allowed the structure of the cofactor to be accessed in its last metastable intermediate state, prior to O-O bond formation. This activated form of the catalyst is geometrically similar to that seen by X ray crystallography, which represents the resting state of the cofactor, but requires the coordination of an additional water molecule to the cofactor, rendering all Mn ions six coordinate. Importantly, it locates two water derived, Mn bound oxygen ligands in close proximity. It is these two oxygen ligands that likely form the product O2 molecule, as proposed earlier by quantum chemical modeling. Current views on the molecular level events that facilitate catalyst activation, that is, catalyst/substrate deprotonation, Mn oxidation and water molecule insertion are briefly described. PMID- 26994743 TI - Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review. AB - OBJECTIVE: To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. DATA SOURCE: The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. DATA SYNTHESIS: Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. CONCLUSIONS: There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required. PMID- 26994745 TI - Optical coherence tomography: A pathway from research to clinical practice. PMID- 26994744 TI - Further delineation of facioaudiosymphalangism syndrome: Description of a family with a novel NOG mutation and without hearing loss. AB - Mutations in the NOG gene give rise to a wide range of clinical phenotypes. Noggin, the protein encoded by this gene is a secreted modulator of multiple pathways involved in both bone and joint development. Proximal symphalangism is commonly observed in patients bearing mutations in this gene, however secondary symptomes are often found including typical facies with hemicylindrical nose with bulbous tip, hyperopia, reduced mobility of multiple joints, hearing loss due to stapes fixation, and recurrent pain from affected joints. With large variation of the phenotype both within and between affected families careful delineation of the genotype-phenotype correlation is needed. In this work we describe a Danish family suffering from SYNS1 due to a novel NOG gene mutation (C230Y). We provide detailed clinical description of the family members presenting rare phenotype of the shoulders shared by affected individuals but no hearing loss, further adding to the phenotypic variability of the syndrome. With these findings we broaden the understanding of NOG-related-symphalangism spectrum disorder. (c) 2016 Wiley Periodicals, Inc. PMID- 26994746 TI - How should we manage thrombosis of Viabahn stent-graft? A case report focused on catheter-directed thrombolysis. AB - PURPOSE: To report a case of a thrombosed GORE(r) VIABAHN(r) endoprosthesis stent graft in the femoral artery (SFA) and popliteal artery managed using the pulse spray technique and complicated by compartment syndrome of the lower leg of the affected limb. CASE REPORT: A 61-year-old woman with three Viabahn stent grafts relining seven bare-metal stents in her right SFA and popliteal artery visited our hospital with complaint of recurrent lifestyle-limiting claudication of right leg. Angiography and intravascular ultrasound showed complete intra-stent obstruction by thrombus from the proximal right SFA to the proximal popliteal artery. Catheter-directed thrombolysis using pulse-spray technique followed by mechanical thrombectomy was performed. Despite successful recanalization, unfortunately, compartment syndrome developed on her right leg on the following day and fasciotomy was performed. CONCLUSION: The larger thrombus burden in Viabahn stent-grafts and its unique physicochemical properties increases the risk for distal embolic complications and potential poor clinical outcomes. PMID- 26994747 TI - Contribution of optical coherence tomography imaging in management of iatrogenic coronary dissection. AB - Iatrogenic coronary dissection is a rare but potentially serious complication of coronary angiography and angioplasty. Treatment with angioplasty guided only by angiography is often difficult. Optical coherence tomography imaging seems to be an interesting technique to lead the management of iatrogenic coronary dissection. Diagnosis can be made by optical coherence tomography; it can also eliminate differential diagnosis. Furthermore, this technique can guide safely the endovascular treatment. PMID- 26994748 TI - Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARalpha in primary human hepatocytes. AB - The ligand-activated nuclear receptor pregnane X receptor (PXR, NR1I2) and the constitutive androstane receptor (CAR, NR1I3) are two master transcriptional regulators of many important drug metabolizing enzymes and transporter genes (DMET) in response to xenobiotics including many drugs. The peroxisome proliferator-activated receptor alpha (PPARalpha, NR1C1), the target of lipid lowering fibrate drugs, primarily regulates fatty acid catabolism and energy homeostasis. Recent research has shown that there are substantial overlaps in the regulated genes of these receptors. For example, both CAR and PXR also modulate the transcription of key enzymes involved in lipid and glucose metabolism and PPARalpha also functions as a direct transcriptional regulator of important DMET genes including cytochrome P450s CYP3A4 and CYP2C8. Despite their important and widespread influence on liver metabolism, comparative data are scarce, particularly at a global level and in humans. The major objective of this study was to directly compare the genome-wide transcriptional changes elucidated by the activation of these three nuclear receptors in primary human hepatocytes. Cultures from six individual donors were treated with the prototypical ligands for CAR (CITCO), PXR (rifampicin) and PPARalpha (WY14,643) or DMSO as vehicle control. Genomewide mRNA profiles determined with Affymetrix microarrays were analyzed for differentially expressed genes and metabolic functions. The results confirmed known prototype target genes and revealed strongly overlapping sets of coregulated but also distinctly regulated and novel responsive genes and pathways. The results further specify the role of PPARalpha as a regulator of drug metabolism and the role of the xenosensors PXR and CAR in lipid metabolism and energy homeostasis. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie. PMID- 26994749 TI - An Aboriginal perspective on 'Closing the Gap' from the rural front line. PMID- 26994750 TI - Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder. AB - Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media 1vid110.1093/brain/aww043_video_abstractaww043_video_abstract. PMID- 26994752 TI - Hydrologic indicators of hot spots and hot moments of mercury methylation potential along river corridors. AB - The biogeochemical cycling of metals and other contaminants in river-floodplain corridors is controlled by microbial activity responding to dynamic redox conditions. Riverine flooding thus has the potential to affect speciation of redox-sensitive metals such as mercury (Hg). Therefore, inundation history over a period of decades potentially holds information on past production of bioavailable Hg. We investigate this within a Northern California river system with a legacy of landscape-scale 19th century hydraulic gold mining. We combine hydraulic modeling, Hg measurements in sediment and biota, and first-order calculations of mercury transformation to assess the potential role of river floodplains in producing monomethylmercury (MMHg), a neurotoxin which accumulates in local and migratory food webs. We identify frequently inundated floodplain areas, as well as floodplain areas inundated for long periods. We quantify the probability of MMHg production potential (MPP) associated with hydrology in each sector of the river system as a function of the spatial patterns of overbank inundation and drainage, which affect long-term redox history of contaminated sediments. Our findings identify river floodplains as periodic, temporary, yet potentially important, loci of biogeochemical transformation in which contaminants may undergo change during limited periods of the hydrologic record. We suggest that inundation is an important driver of MPP in river corridors and that the entire flow history must be analyzed retrospectively in terms of inundation magnitude and frequency in order to accurately assess biogeochemical risks, rather than merely highlighting the largest floods or low-flow periods. MMHg bioaccumulation within the aquatic food web in this system may pose a major risk to humans and waterfowl that eat migratory salmonids, which are being encouraged to come up these rivers to spawn. There is a long-term pattern of MPP under the current flow regime that is likely to be accentuated by increasingly common large floods with extended duration. PMID- 26994751 TI - Conversion to mTOR-inhibitors with calcineurin inhibitor elimination or minimization reduces urinary polyomavirus BK load in kidney transplant recipients. AB - BACKGROUND/PURPOSE: Polyomavirus BK (BKV) reactivation causes allograft dysfunction in some kidney transplant recipients. The use of mammalian target of rapamycin (mTOR) inhibitor-based immunotherapy is associated with a lower incidence of polyomavirus-associated nephropathy compared with other immunosuppressants. This retrospective study assessed whether conversion to mTOR inhibitor-based immunotherapy directly reduced urinary BKV load. METHODS: A total of 63 kidney recipients were divided into mTOR inhibitor-conversion (21 patients) and nonconversion (42 patients) groups. Urinary BKV loads were determined before and at least 6 months after the conversion. RESULTS: The results demonstrated that urinary BKV titer was significantly reduced in the conversion group (3.94 +/ 0.43 copies (log)/mL to 2.49 +/- 0.19 copies (log)/mL) and remained unaltered in the nonconversion group (3.19 +/- 0.20 copies (log)/mL to 2.90 +/- 0.20 copies (log)/mL). In addition, the percentage of patients with reduced urinary BKV load was significantly higher in the conversion group (76.2% vs. 42.9%). The estimated glomerular filtration rate after 24 months mTOR inhibitor conversion was significantly increased compared with that in the nonconversion group. Conversion to mTOR-inhibitor-based immunotherapy was the only factor associated with an increase in estimated glomerular filtration rate. CONCLUSION: This study reveals an association of conversion to mTOR-inhibitor-based immunotherapy with the reduction of urinary BKV load. PMID- 26994753 TI - Study of a 10B+ZnS(Ag) neutron detector as an alternative to 3He-based detectors in Homeland Security. AB - The response of a scintillation neutron detector of ZnS(Ag) with 10B was calculated, using the MCNPX Monte Carlo Code. The detector consists of four panels of polymethyl methacrylate (PMMA) and five thin layers of ~0.017cm thick 10B+ZnS(Ag) in contact with the PMMA. The response was calculated for the bare detector and with different thicknesses of High Density Polyethylene, HDPE, moderator for 29 monoenergetic sources as well as 241AmBe and 252Cf neutrons sources. In these calculations the reaction rate 10B(n, alpha)7Li and the neutron fluence in the sensitive area of the detector 10B+ZnS(Ag) was estimated. Measurements were made at the Neutron Measurements Laboratory, Universidad Politecnica de Madrid, LMN-UPM, to quantify the detections in counts per second in response to a 252Cf neutron source separated 200cm. The MCNPX computations were compared with measurements to estimate the efficiency of ZnS(Ag) for detecting the alpha that is created in the 10B(n, alpha)7Li reaction. After validating new models with different geometries it will be possible to improve the detector response trying to achieve a sensitivity of 2.5cps-ng252Cf comparable with the response requirements for 3He detectors installed in the Radiation Portal Monitors, RPMs. This type of detector can be considered an alternative to the 3He detectors for detection of Special Nuclear Material, SNM. PMID- 26994754 TI - Diagnostic radiology dosimetry: Status and trends. AB - Since 1970s the expression of protection standards shifted from a dose -to a risk based approach, with dose limits established to yield risks to medical radiation workers. Worldwide interest in patient dose measurement was stimulated by the publication of Patient Dose Reduction in Diagnostic Radiology by the UK National Radiological Protection Board (NRPB). This has resulted in the development of new dosimetric measuring instruments, techniques and terminologies which present challenges to those working in the clinic al environment and those supporting them in calibration facilities. In this sense, thermoluminescent dosimetry (TLD) has been actively developed in the past last 3 decades thanks to their successful applications in diagnostic radiology. The present work analyzes current status and future trends of diagnostic radiology dosimetry using thermoluminescence phenomena. PMID- 26994755 TI - Assessment of patient dose and radiogenic risks during endoscopic retrograde cholangiopancreatography. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive technique that has been used for over 30 years in the diagnosis and management of pancreaticobiliary disorders. The objectives of this study were to evaluate the patient entrance surface air kerma doses (ESAK) and estimate the organ and effective doses during ERCP in three hospitals in Khartoum. A total of 55 patients were examined in three hospitals in Khartoum state, Sudan. Calibrated thermoluinescent dosimeters (TLD) were used to measure patients' ESAK. Organ and effective doses were estimated using National Radiological Protection Board (NRPB) software. The overall mean of ESAK for all ERCP procedures was 42.4mGy. The mean patient ESAK in Fedail (A), Soba (B) and Ibn sena (C) hospitals were 26.7mGy, 26.0mGy and 72.4mGy, respectively. The effective doses in three hospitals were 1.60, 1.56 and 2.67mSv in that order and the overall mean effective dose was 1.94mSv. Patient radiation doses vary widely among the hospitals. Patient ESAK is low compared to previous studies in the light of the current practice. Patient dose was decreased significantly in the last two decades. PMID- 26994756 TI - Driving pressure during assisted mechanical ventilation: Is it controlled by patient brain? AB - Tidal volume (VT) is the controlled variable during passive mechanical ventilation (CMV) in order to avoid ventilator-induced-lung-injury. However, recent data indicate that the driving pressure [DeltaP; VT to respiratory system compliance (Crs) ratio] is the parameter that best stratifies the risk of death. In order to study which variable (VT or DeltaP) is controlled by critically ill patients, 108 previously studied patients were assigned to receive PAV+ (a mode that estimates Crs and permits the patients to select their own breathing pattern) after CMV, were re-analyzed. When patients were switched from CMV to PAV+ they controlled DeltaP without constraining VT to narrow limits. VT was increased when the resumption of spontaneous breathing was associated with an increase in Crs. When DeltaP was high during CMV, the patients (n=12) decreased it in 58 out of 67 measurements. We conclude that critically ill patients control the driving pressure by sizing the tidal volume to individual respiratory system compliance using appropriate feedback mechanisms aimed at limiting the degree of lung stress. PMID- 26994757 TI - Inspiratory muscle performance in endurance-trained elderly males during incremental exercise. AB - The aim of this study was to compare the inspiratory muscle performance during an incremental exercise of twelve fit old endurance-trained athletes (OT) with that of fit young athletes (YT) and healthy age-matched controls (OC). The tension time index (TT0.1) was determined according to the equation TT0.1=P0.1/PImax*ti/ttot, where P0.1 is the mouth occlusion pressure, PImax the maximal inspiratory pressure and ti/ttot the duty cycle. For a given VCO2, OT group displayed P0.1, P0.1/PImax ratio, TT0.1 and effective impedance of the respiratory muscle values which were lower than OC group and higher than YT group. At maximal exercise, P0.1/PImax ratio and TT0.1 was still lower in the OT group than OC group and higher than YT group. This study showed lower inspiratory muscle performance attested by a higher (TT0.1) during exercise in the OT group than YT group, but appeared to be less marked in elderly men having performed lifelong endurance training compared with sedentary elderly subjects. PMID- 26994758 TI - The Registered Dietitian Nutritionist's Guide to Homemade Tube Feeding. PMID- 26994759 TI - Awakening Blood Pressure Rise in a Patient with Spinal Cord Injury. AB - BACKGROUND: The pathophysiological mechanism causing awakening blood pressure (BP) rise is not clear. CASE REPORT: We report the case of a 66-year-old man with a history of spinal cord injury, and who had remarkable awakening BP rise in ambulatory BP monitoring. The patient also had orthostatic hypotension and post prandial hypotension associated with an increased insulin level. This case suggests that awakening BP rise can occur without increased physical activity or positional changes, in those with autonomic nerve dysreflexia associated with a spinal cord injury. The reduction of elevated awakening BP level can be affected by eating breakfast in association with an increased insulin level. However, in ambulatory BP monitoring, the awakening BP rise was reproducible, but this patient also exhibited evening BP rise in home BP monitoring when he took a nap. CONCLUSIONS: Exaggerated awakening BP rise can occur in patients with spinal cord injury without positional change, and the recovery of BP may be modified by post prandial and orthostatic BP drop. PMID- 26994760 TI - [Interannual variation of the fungal spores of Tetouan (Northwest of Morocco) and their sporal calendar]. AB - THE AIM: The daily aeromycological monitoring of fungal spores in the city of Tetouan during the period 2009-2011, to determine their diversity, their predominance and their interannual and seasonal variation. MATERIAL AND METHODS: The spore sampling was undertaken using a Burkard volumetric spore trap. RESULTS: The outdoor environment of Tetouan showed a highest predominance of deuteromycetes, collected essentially in summer and autumn. This study illustrated a high diversity of the fungal spores, the most frequent accounting for more than 97 % of the airborne fungal flora, and are according to their abundance (Cladosporium followed by Basidiospores, Ustilago, Alternaria, Leptosphaeria, Aspergillaceae, Cunninghamella, Venturia, Uredospores, Pleospora, Arthrinium, Stemphylium, Torula, Oidium, Ascospores, Drechslera, Epicoccum, Teleutospores and Fusarium). Alternaria and Cladosporium showed a longer period of emission, and are present in the atmosphere throughout the year with the highest incidence for Alternaria in June and for Cladosporium in August. They exceeded the allergenic threshold value in the air of Tetouan during 22, 94 and 75 days in 2009, 2010 and 2011 respectively for Alternaria and during 16 days in 2009, 14 days in 2010 and 13 days in 2011 for Cladosporium. The correlation between the meteorological parameters and the fungal spores proved that the temperature (maximum, average and minimum), the relative humidity (maximum, average and minimum) and the precipitation influenced the presence of the fungal spores in the air. CONCLUSION: The exposition to airborne fungal spores varied between years depending on local climatic conditions and might cause health impacts on patients showing respiratory allergy. PMID- 26994761 TI - [Does the sampling locality influence on the antifungal activity of the flavonoids of Marrubium vulgare against Aspergillus niger and Candida albicans?]. AB - OBJECTIVE: The study was undertaken to determine the effect of the sampling locality on the antifungal activity of the flavonoids extracted from the leaves of Marrubium vulgare L. against two fungal strains; Aspergillus niger ATCC 16404 and Candida albicans ATCC 10231. MATERIALS AND METHODS: The leaves were collected from three different sampling localities belonging northwest Algeria: Tessala mount, M'sila forest and Ain Skhouna. The flavonoid extraction was carried out by using organic solvents with increasing polarity. A phytochemical screening was performed by staining test tubes. The inhibition diameters were measured by solid medium diffusion method. The minimum inhibitory concentrations were determined by dilution method on solid medium. RESULTS: The antifungal activity varied significantly (P<0.001) according to the sampling locality of the leaves, the flavonoid extract and its concentration, and the strain fungal type. The inhibition diameters varied between 8.16 and recorded 37.5mm even recording a total inhibition of fungal growth and often exceed those induced marketed antifungals (Amphotericin, Fluconazole, Terbinafine and econazole nitrate). The minimum inhibitory concentrations (MICs) obtained range between 6.25 and 100MUg/mL; experiencing strong antifungal inhibition. The phytochemical screening revealed the existence of certain flavonoids classes such as flavans and flavanols which may be responsible of this remarkable antifungal power. CONCLUSION: The sampling locality of Marrubium vulgare leaves influenced on the antifungal activity of flavonoids. These have proven very good fungistatic and worth valuing in pharmacology. PMID- 26994762 TI - Are people following hip and knee arthroplasty at greater risk of experiencing a fall and fracture? Data from the Osteoarthritis Initiative. AB - INTRODUCTION: Falls are a major challenge for older people and are a significant source of mortality and morbidity. There has been uncertainty as to whether people with total hip (THA) or knee (TKA) arthroplasty have a greater risk of falls and associated fractures. This analysis was to explore this question with a large community dataset. MATERIALS AND METHODS: Data from all people enroled onto the US Osteoarthritis Initiative programme who had undergone a THA (n = 104) or TKA (n = 165), within a 12-month period, were compared to those who had not undergone an arthroplasty (n = 4631). Data were collected on: the number of participants who reported a fall within a 12-month period; the frequency of falls in this period; and whether a fracture was sustained during this period. Odd ratios were calculated for the probability of experiencing a fall or fracture between the groups. RESULTS: There was no statistical difference in falls between people following THA (OR 0.90; 95 % CI 0.58-1.41) or TKA (OR 0.95; 0.67-1.35) compared to a non-arthroplasty cohort. Whilst there was no statistical difference in fracture risk between people following TKA compared to non-arthroplasty individuals (OR 1.25; 95 % CI 0.57-2.70), those who underwent THA had a 65 % lower chance of experiencing a fracture in the initial 12 post-operative months compared to the non-THA cohort (OR 0.35; 95 % CI 0.19-0.65; p < 0.01). CONCLUSIONS: There appears a lower chance of experiencing a fracture for people following THA compared to those who have not. PMID- 26994764 TI - Epidemiologic research topics in Germany: a keyword network analysis of 2014 DGEpi conference presentations. AB - Knowledge of epidemiologic research topics as well as trends is useful for scientific societies, researchers and funding agencies. In recent years researchers recognized the usefulness of keyword network analysis for visualizing and analyzing scientific research topics. Therefore, we applied keyword network analysis to present an overview of current epidemiologic research topics in Germany. Accepted submissions to the 9th annual congress of the German Society for Epidemiology (DGEpi) in 2014 were used as data source. Submitters had to choose one of 19 subject areas, and were ask to provide a title, structured abstract, names of authors along with their affiliations, and a list of freely selectable keywords. Keywords had been provided for 262 (82 %) submissions, 1030 keywords in total. Overall the most common keywords were: "migration" (18 times), "prevention" (15 times), followed by "children", "cohort study", "physical activity", and "secondary data analysis" (11 times each). Some keywords showed a certain concentration under one specific subject area, e.g. "migration" with 8 of 18 in social epidemiology or "breast cancer" with 4 of 7 in cancer epidemiology. While others like "physical activity" were equally distributed over multiple subject areas (cardiovascular & metabolic diseases, ageing, methods, paediatrics, prevention & health service research). This keyword network analysis demonstrated the high diversity of epidemiologic research topics with a large number of distinct keywords as presented at the annual conference of the DGEpi. PMID- 26994763 TI - Nosocomial Bloodstream Infection Due to Candida spp. in China: Species Distribution, Clinical Features, and Outcomes. AB - OBJECTIVES: To investigate the distribution of Candida spp., predictors of mortality, and effects of therapeutic measures on outcomes of nosocomial bloodstream infection (BSI) due to Candida spp. METHODS: This retrospective, population-based study enrolled adult patients with Candida nosocomial BSI from January 2010 to December 2014 in one tertiary care hospital. The demographics, comorbidities, species distribution, risk factors, and effects of antifungal treatment were assessed. RESULTS: In total, 190 episodes of Candida BSI were identified. The most prevalent species was C. albicans (38.9 %), followed by C. parapsilosis (23.2 %) and C. tropicalis (20.5 %). In vitro susceptibility testing showed that 88.9 % of Candida isolates were susceptible to fluconazole. The 30 day hospital mortality was 27.9 %, while the early mortality (within 7 days) was 16.3 %. In a multivariate regression analysis, the Acute Physiology and Chronic Health Evaluation II score [odds ratio (OR) 1.23; 95 % confidence interval (CI) 1.080-1.390; P = 0.002] and severe sepsis or septic shock (OR 15.35; 95 % CI 2.391-98.502; P = 0.004) were independently correlated with early mortality. Severe sepsis or septic shock (OR 24.75; 95 % CI 5.099-120.162; P < 0.001) was an independent risk factor for 30-day mortality, while proven catheter-related candidemia (OR 0.16; 95 % CI 0.031-0.810; P = 0.027) was a positive factor for 30 day mortality. Early central venous catheter removal and adequate antifungal treatment were closely related to decreased mortality in patients with primary candidemia. CONCLUSION: The proportion of candidemia caused by C. albicans was lower than that caused by non-albicans species. The severity of illness influenced early mortality, and the origin of the central venous catheter remarkably affected 30-day mortality. PMID- 26994765 TI - Implanting straight into cochlea risks the facial nerve: a Cartesian coordinate study. AB - PURPOSE: To describe the straight-into-cochlea line that affords the best access for an electrode array to enter via the round window, and how this line relates to the facial nerve, the incus, and mastoid size. The straight-into-cochlea line is important to minimize the cochlear trauma and maximize the likelihood of placement into the scala tympani. METHODS: High-resolution CT scans were obtained for ten craniums with the extremes of large (N = 5) and small (N = 5) mastoid pneumatization; the specimens were from a series of 41 ear normal craniums. Using FIJI, a publicly available software program, the straight-into-cochlea insertion line was determined by defining the x-y-z coordinates of the middle of the round window and a point 6.0 mm into the cochlea on its centrifugal wall. Then, from the extended straight-into-cochlea insertion line, we determined the shortest perpendicular distance to the middle of the fallopian canal, and from that "fallopian point" to the apex of the posterior process of the incus. RESULTS: We found good repeatability of measurements. We found the extended straight-into cochlea insertion lines routinely close to or in the midst of the fallopian canal (50 % <= 1.0 mm). We found the lines 4.7-7.8 mm from the apex of the posterior process of the incus. Line positions relative to "fallopian point" and incus showed no relation to mastoid pneumatization. For the distance "fallopian point" to incus, bilateral symmetry was suggested. CONCLUSIONS: Using landmarks registered in an x-y-z coordinate system, straight-into-cochlea insertion via the round window puts the facial nerve at risk. PMID- 26994766 TI - Using morbidity and income data to forecast the variation of growth and employment in the oral healthcare sector. AB - The perception of the health sector from an economic policy point of view is changing. In the past, health expenditure was mostly seen as a "cost" item, probably because many medical treatments are covered by public health insurance. However, policymakers are increasingly realizing that a growing health sector may be quite beneficial for an economy. It creates employment opportunities and it is relatively resistant to the fluctuations of the business cycle. Input-output analysis could be a useful tool to study the structural change resulting from the growth of the health sector. This paper quantifies for the first time the economic significance of the oral healthcare sector as a component of the German healthcare sector as a whole. The current data for the healthcare sector comes from Health Satellite Accounts, which while comprehensive do fail to answer important questions due to not incorporating certain sectors such as the oral healthcare sector. Therefore on the basis of the Health Satellite Account a specific Satellite Account for the oral healthcare sector is created by using billing data as well as epidemiological data, provided by several dental associations and the Institute of German Dentists. Based on this added information, gross value added data and the number of employees in the oral healthcare sector are computed. Gross value added in 2010 amounted to ?13.4 billion, with around ?4 billion being attributable to the secondary oral healthcare market; the market for solely out-of-pocket payments. In a second step the paper develops a model to forecast oral healthcare sector growth based on various explanatory variables such as demographic change, take-up behaviour, medical-technical progress, oral morbidity, aggregated supply (collective dental treatment times) as well as income levels and distribution, where the latter two are considered to be of particular importance. According to this model, by 2030 gross value added in the oral healthcare sector will amount to ?15.9 million, which corresponds to a 19.2 % increase. The secondary oral healthcare market will be the key to this increase since the model predicts a disproportionately high growth of 60.3 % bringing the total to ?6.3 million gross value added in 2030. PMID- 26994767 TI - Seed specific expression and analysis of recombinant human adenosine deaminase (hADA) in three host plant species. AB - The plant seed is a leading platform amongst plant-based storage systems for the production of recombinant proteins. In this study, we compared the activity of human adenosine deaminase (hADA) expressed in transgenic seeds of three different plant species: pea (Pisum sativum L.), Nicotiana benthamiana L. and tarwi (Lupinus mutabilis Sweet). All three species were transformed with the same expression vector containing the hADA gene driven by the seed-specific promoter LegA2 with an apoplast targeting pinII signal peptide. During the study, several independent transgenic lines were generated and screened from each plant species and only lines with a single copy of the gene of interest were used for hADA expression analysis. A stable transgenic canola line expressing the ADA protein, under the control of 35S constitutive promoter was used as both as a positive control and for comparative study with the seed specific promoter. Significant differences were detected in the expression of hADA. The highest activity of the hADA enzyme (Units/g seed) was reported in tarwi (4.26 U/g) followed by pea (3.23 U/g) and Nicotiana benthamiana (1.69 U/g). The expression of mouse ADA in canola was very low in both seed and leaf tissue compared to other host plants, confirming higher activity of seed specific promoter. Altogether, these results suggest that tarwi could be an excellent candidate for the production of valuable recombinant proteins. PMID- 26994768 TI - Transabdominal sacrocolpopexy with autologous rectus fascia graft. AB - INTRODUCTION AND HYPOTHESIS: Extrusion and infection are potential postoperative complications when using synthetic mesh for abdominal sacrocolpopexy. Long-term follow-up in the Colpopexy and Urinary Reduction Efforts (CARE) trial revealed an estimated 9.9 % risk of mesh extrusion. There are 26 reports of spondylodiscitis after sacrocolpopexy with synthetic mesh. These surgical risks may be decreased by using autologous fascia. To date, there have been no reports of extrusion or spondylodiscitis after using autologous fascia for sacrocolpopexy. METHODS: This video demonstrates transabdominal sacrocolpopexy with an autologous rectus fascia graft. A 76-year-old woman with symptomatic stage 3 prolapse also had a history of diverticulitis and sigmoid abscess requiring sigmoid colectomy with end colostomy and incidental left ureteral transection with subsequent left nephrostomy tube placement. She presented for colostomy reversal, ureteral reimplantation, and prolapse repair. Given the need for concomitant colon and ureteral reconstruction, the risk of infection was potentially higher if synthetic mesh were used. The patient therefore underwent transabdominal sacrocolpopexy with autologous rectus fascia graft. RESULTS: At 4 months' follow up the patient reported resolution of her symptoms and on examination she had no pelvic organ prolapse. CONCLUSION: Transabdominal sacrocolpopexy using autologous rectus fascia graft is a feasible option, especially in cases in which infection and synthetic mesh extrusion risks are potentially higher. PMID- 26994769 TI - Increases in M-wave latency of biceps brachii after elbow flexor eccentric contractions in women. AB - PURPOSE: Eccentric contractions (ECCs) induce muscle damage that is indicated by prolonged loss of muscle function and delayed onset muscle soreness. It is possible that ECCs affect motor nerves, and this may contribute to the prolonged decreases in force generating capability. The present study investigated the hypothesis that M-wave latency of biceps brachii would be increased after maximal elbow flexor ECCs resulting in prolonged loss of muscle strength. METHODS: Fifteen women performed exercise consisting of 60 maximal ECCs of the elbow flexors using their non-dominant arm. M-wave latency was assessed by the time taken from electrical stimulation applied to the Erb's point to the onset of M wave of the biceps brachii before, immediately after, and 1-4 days after exercise. Maximal voluntary isometric contraction (MVC) torque, range of motion (ROM) and muscle soreness using a numerical rating scale were also assessed before and after exercise. RESULTS: Prolonged decreases in MVC torque (1-4 days post-exercise: -54 to -15 %) and ROM (1-2 days: -32 to -22 %), and increased muscle soreness (peak: 4.2 out of 10) were evident after exercise (p < 0.05). The M-wave latency increased (p < 0.01) from 5.8 +/- 1.0 ms before exercise to 6.5 +/ 1.7 ms at 1 day and 7.2 +/- 1.5 ms at 2 days after exercise for the exercised arm only. No significant changes in M-wave amplitude were evident after exercise. CONCLUSION: The increased M-wave latency did not fully explain the prolonged decreases in MVC torque after eccentric exercise, but may indicate reversible motor nerve impairment. PMID- 26994770 TI - Different Zinc Sources Have Diverse Impacts on Gene Expression of Zinc Absorption Related Transporters in Intestinal Porcine Epithelial Cells. AB - This study was conducted to investigate the effects of zinc sources on gene expression of zinc-related transporters in intestinal porcine epithelial cells (IPEC-1). IPEC-1 cells were treated with zinc glycine chelate (Zn-Gly), zinc methionine (Zn-Met), and zinc sulfate (ZnSO4), respectively, for measurement of cell viability. Then, the relative expression of zinc-related transporters in IPEC-1 in response to different zinc sources (50 MUmol/L zinc) was measured. Zinc transporter SLC39A4 (ZIP4) expression was selectively silenced to assess the function of ZIP4 in inorganic and organic zinc absorption. The result showed that Zn-Gly and Zn-Met had lower cell damage compared with ZnSO4 on the same zinc levels. Different zinc sources improved the expression of metallothionein1 (MT1) and zinc transporter SLC30A1 (ZnT1) messenger RNA (mRNA) compared with the control (P < 0.05), while ZIP4 decreased (P < 0.05) in response to zinc addition. MT1 and ZnT1 mRNA expressions in Zn-Gly and Zn-Met were higher than those in ZnSO4, and ZIP4 mRNA expression in Zn-Met was the lowest among three kinds of zinc sources (P < 0.05). Expression of divalent metal transporter 1 (DMT1) mRNA in control was significantly higher (P < 0.05) than added different zinc sources groups. Silencing of ZIP4 significantly decreased MT1 mRNA expression in ZnSO4 and Zn-Gly treatments, reduced zinc absorption rate, and increased DMT1 mRNA expression in ZnSO4 compared with negative control. In summary, different zinc sources could improve zinc status on IPEC-1 cells and organic zinc had lower cell damage compared with ZnSO4. Moreover, Zn-Gly and Zn-Met are more efficient on zinc absorption according to the expression of various zinc-related transporters MT1, ZIP4, ZnT1, and DMT1. ZIP4 played a direct role in inorganic zinc uptake, and the absorption of zinc in Zn-Gly depends on ZIP4 partly, while absorption of Zn-Met is less dependent on ZIP4. PMID- 26994771 TI - Secreted expression of truncated capsid protein from porcine circovirus type 2 in Pichia pastoris. AB - OBJECTIVE: To achieve secreted expression of the truncated capsid protein from porcine circovirus type 2 (PCV2) in Pichia pastoris. RESULTS: A truncated cap gene (tcap) with a deleted N-terminal nuclear localization signal was optimized and synthesized. Effective secreted expression was achieved in P. pastoris GS115. The high-productive recombinant strain for tCap was grown in a 5 l bioreactor and the productivity of tCap in supernatant reached 250 MUg/ml. Furthermore, serum antibody test demonstrated that adjuvant-assisting tCap induced a significant increase of specific PCV2-Cap antibody over time in mice and a similar antibody level in pigs compared with a commercial Cap-based subunit vaccine. CONCLUSION: This work establishes a secreted expression strategy in P. pastoris for the production of PCV2 Cap with superior bioactivity, and this strategy might provide potential uses in developing Cap-based subunit vaccine in the future. PMID- 26994773 TI - What are the prospects for non-scheduled robotic procedures in pediatric surgery? AB - Robotic technology allows for the management of complex surgical cases with a minimally invasive approach. The aim of this study was to communicate our experience using robotic technology for non-scheduled pediatric procedures (NSP). We performed a prospective study over the last 5 years including all consecutive cases where surgery was performed with a robot. NSP procedures were defined as a time to surgery of <24 h. Preoperative time, operative time, overall completion rate, and postoperative course were analyzed. Of the 85 cases recorded, five corresponded to robot-assisted NSP with a mean weight of 10 kg (3-36 kg). The mean time before surgery was 19 h (11-24 h). Conversion rate to open procedure was 40 %. Fifteen NSP had to be performed without robotic plateform. Robotic surgery is a potentially relevant option for most pediatric thoracic or abdominal procedures performed in a non-scheduled setting and offers technical advantages. PMID- 26994772 TI - Gut microbiome diversity in acute infective and chronic inflammatory gastrointestinal diseases in North India. AB - The disease profile in the Indian population provides a unique opportunity for studying the host microbiome interaction in both infectious (amebiasis) and autoimmune diseases like inflammatory bowel disease (IBD) from a similar environment and genetic background. Analysis of fecal samples from untreated amebic liver abscess (ALA) patients, Entamoeba histolytica (Eh)-negative and positive asymptomatic individuals, and pus samples from naive ALA patients revealed a significant reduction in Lactobacillus in asymptomatic individuals (Eh +ve) and ALA patients. Two anaerobic genera, namely Bacteroides and Peptostreptococcus, were detected in naive ALA pus samples. Analysis of fecal samples from amoebic colitis patients showed a significant decline in population of Bacteroides, Clostridium coccoides and leptum subgroup, Lactobacillus, Campylobacter, and Eubacterium, whereas a significant increase in Bifidobacterium was observed. Mucosa-associated bacterial flora analysis from IBD patients and healthy controls revealed a significant difference in concentration of bacteria among predominating and subdominating genera between ulcerative colitis (UC), Crohn's disease (CD) patients, and controls. In contrast to the mucosal studies, we found a significant increase in lactobacilli population in fecal samples of active UC patients. Another study revealed a significant decrease of Clostridium coccoides and leptum clusters in fecal samples of active UC patients along with decreased concentrations of fecal SCFAs, especially of n-butyrate, iso-butyrate, and acetate. We therefore found similar perturbations in gut microbiome in both infectious and autoimmune diseases, indicating inflammation to be the major driver for changes in gut microbiome. PMID- 26994774 TI - Implementing a robotics curriculum at an academic general surgery training program: our initial experience. AB - The robotic surgical platform is being utilized by a growing number of hospitals across the country, including academic medical centers. Training programs are tasked with teaching their residents how to utilize this technology. To this end, we have developed and implemented a robotic surgical curriculum, and share our initial experience here. Our curriculum was implemented for all General Surgical residents for the academic year 2014-2015. The curriculum consisted of online training, readings, bedside training, console simulation, participating in ten cases as bedside first assistant, and operating at the console. 20 surgical residents were included. Residents were provided the curriculum and notified the department upon completion. Bedside assistance and operative console training were completed in the operating room through a mix of biliary, foregut, and colorectal cases. During the fiscal years of 2014 and 2015, there were 164 and 263 robot-assisted surgeries performed within the General Surgery Department, respectively. All 20 residents completed the online and bedside instruction portions of the curriculum. Of the 20 residents trained, 13/20 (65 %) sat at the Surgeon console during at least one case. Utilizing this curriculum, we have trained and incorporated residents into robot-assisted cases in an efficient manner. A successful curriculum must be based on didactic learning, reading, bedside training, simulation, and training in the operating room. Each program must examine their caseload and resident class to ensure proper exposure to this platform. PMID- 26994775 TI - Significance of erection hardness score as a diagnostic tool to assess erectile function recovery in Japanese men after robot-assisted radical prostatectomy. AB - The objective of this study was to characterize time-dependent recovery of erectile function in Japanese patients following robot-assisted radical prostatectomy (RARP) using the erection hardness score (EHS). This study prospectively included 170 Japanese patients with localized prostate cancer (PC) undergoing RARP without neoadjuvant hormonal therapy. The erectile function of each patient was assessed based on the International Index of Erectile Function-5 (IIEF-5) and EHS at the baseline and on every visit to an outpatient clinic after RARP. In this series, potency was defined as the ability to have an erection sufficient for intercourse, corresponding to EHS >=3, while patients with EHS >=2 were regarded as those with erectile function. Of these 170 patients, 20 and 75 underwent bilateral and unilateral nerve-sparing procedures, respectively; however, non-nerve-sparing procedures were performed in the remaining 75. A proportional increase in the IIEF-5 score according to EHS was noted at 24 months after RARP. At 6, 12 and 24 months after RARP, the recovery rates of erectile function were 11.9, 21.7 and 35.8 %, respectively, while those of potency were 3.8, 9.8 and 13.7 %, respectively. Of several factors examined, the age, preoperative IIEF-5 score and nerve-sparing procedure were identified as independent predictors of erectile function recovery. These findings suggest that favorable erectile function recovery could not be achieved in Japanese PC patients even after the introduction of RARP; therefore, it might be preferable for such a cohort to use EHS rather than IIEF-5 as an assessment tool for the postoperative recovery of erectile function. PMID- 26994776 TI - Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy. AB - To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 +/- 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 +/- 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss. PMID- 26994777 TI - Outcomes of patients with severe sepsis after the first 6 hours of resuscitation at a regional referral hospital in Uganda. AB - INTRODUCTION: The optimal resuscitation strategy for patients with severe sepsis in resource-limited settings is unknown. Therefore, we determined the association between intravenous fluids, changes in vital signs and lactate after the first 6 hours of resuscitation from severe sepsis, and in-hospital mortality at a hospital in Uganda. MATERIALS AND METHODS: We enrolled patients admitted with severe sepsis to Mbarara Regional Referral Hospital and obtained vital signs and point-of-care blood lactate concentration at admission and after 6 hours of resuscitation. We used logistic regression to determine predictors of in-hospital mortality. RESULTS: We enrolled 218 patients and had 6 hour postresuscitation data for 202 patients. The median (interquartile range) age was 35 (26-50) years, 49% of patients were female, and 57% were HIV infected. The in-hospital mortality was 32% and was associated with admission Glasgow Coma Score (adjusted odds ratio [aOR], 0.749; 95% confidence interval [CI], 0.642-0.875; P < .001), mid-upper arm circumference (aOR, 0.876; 95% CI, 0.797-0.964; P = .007), and 6-hour systolic blood pressure (aOR, 0.979; 95% CI, 0.963-0.995; P = .009) but not lactate clearance of 10% or greater (aOR, 1.2; 95% CI, 0.46-3.10; P = .73). CONCLUSIONS: In patients with severe sepsis in Uganda, obtundation and wasting were more closely associated with in-hospital mortality than lactate clearance of 10% or greater. PMID- 26994778 TI - Detecting central-venous oxygen desaturation without a central-venous catheter: Utility of the difference between invasively and noninvasively measured blood pressure. AB - OBJECTIVE: The objective was to determine whether central-venous oxygen saturation (ScvO2<70%) can be detected from the difference between invasively and noninvasively measured systolic blood pressure (BP) (ie, DeltaBP defined as arterial BP minus noninvasive BP). METHODS: This is a cross-sectional study at a single medical and surgical intensive care unit in Japan. All hypotensive patients admitted to intensive care unit were eligible. Arterial BP was measured via a radial-artery catheter, and noninvasive BP on the same side was measured via a brachial cuff. ScvO2 was measured by gas analysis of blood sampled from a central-venous chatheter (CVC). We calculate the area under the curve for DeltaBP as an indicator of ScvO2<70%. RESULTS: Usable data were obtained from the records of 111 patients. The median and interquartile range of DeltaBP and ScvO2 were 4mm Hg (-11, 6) and 67% (60.9, 73.9), respectively. The area under the curve of DeltaBP as an indicator of ScvO2<70% was 0.81 (95% confidence interval [CI], 0.73 0.89). With a cutoff DeltaBP of 0, sensitivity was 65.7% (95% CI, 53.1-76.8), specificity was 97.7% (95% CI, 88.0-99.8), and positive predictive value was 97.8 (95% CI, 88.2-99.9). CONCLUSIONS: DeltaBP can indicate whether ScvO2 is lower than 70%. When that difference is greater than 0, ScvO2 is very likely to be lower than 70%. PMID- 26994779 TI - Clinical application of the ProVent score in Korean patients requiring prolonged mechanical ventilation: A 10-year experience in a university-affiliated tertiary hospital. AB - PURPOSE: We evaluated the clinical usefulness of a prognostic scoring system ("the ProVent score") in Korean patients requiring prolonged mechanical ventilation. MATERIAL AND METHODS: We retrospectively analyzed the data of 184 patients in a medical intensive care unit of a tertiary care hospital between January 2004 and December 2013. RESULTS: The patients' median age was 65 years, and 66.8% were male. One-year mortality was 67.4%. On day 21 of mechanical ventilation, the ProVent score was 0 in 13 patients (7.1%), 1 in 39 patients (21.2%), 2 in 73 patients (39.7%), 3 in 42 patients (22.8%), and greater than or equal to 4 in 17 patients (9.2%). For patients with a ProVent score ranging from 0 to greater than or equal to 4, 1-year mortality was 46.2%, 53.8%, 68.5%, 76.2%, and 88.2%, respectively. The Kaplan-Meier curves of 1-year survival for each ProVent score showed statistically significant differences (log-rank test: P = .001). Logistic regression analysis showed that only thrombocytopenia was independently associated with 1-year mortality in our cohort (odds ratio = 4.786, P < .001). CONCLUSIONS: In our study, the ProVent score could be applied to predict 1-year mortality for patients requiring prolonged mechanical ventilation in Korea. Among variables contributing to this score, only thrombocytopenia was an independent prognostic factor for 1-year mortality. PMID- 26994781 TI - Ready and waiting: Freezing as active action preparation under threat. AB - Freezing is a defensive response characterized by rigidity and bradycardia, but it is unclear whether it is a passive versus active preparatory state. We developed a shooting task in which preparation and threat were manipulated independently: Participants were either helpless or able to respond to a possible upcoming attack, and attacks were either associated with an electric shock or not. Essentially, a purely anticipatory preparatory period was used during which no stimuli occurred. Freezing was assessed during this period. In addition to heart rate, body sway was measured, using a stabilometric force platform. The efficacy of the threat manipulation was confirmed via self-report. The ability to prepare led to decreases in heart rate and postural sway, while threat led to decreased heart rate. Further, exploratory analyses suggested that aggressive participants showed reduced initial freezing for threatening opponents, but increased postural freezing when armed. The results suggest that freezing may involve active preparation. Relations to results in passive viewing tasks are discussed. PMID- 26994780 TI - Psoas Muscle Cross-sectional Area as a Measure of Whole-body Lean Muscle Mass in Maintenance Hemodialysis Patients. AB - OBJECTIVE: We investigate whether psoas or paraspinous muscle area measured on a single L4-L5 image is a useful measure of whole lean body mass (LBM) compared to dedicated midthigh magnetic resonance imaging (MRI). DESIGN: Observational study. SETTING: Outpatient dialysis units and a research clinic. SUBJECTS: One hundred five adult participants on maintenance hemodialysis. No control group was used. INTERVENTION: Psoas muscle area, paraspinous muscle area, and midthigh muscle area (MTMA) were measured by magnetic resonance imaging. MAIN OUTCOME MEASURE: LBM was measured by dual-energy absorptiometry scan. RESULTS: In separate multivariable linear regression models, psoas, paraspinous, and MTMA were associated with increase in LBM. In separate multivariate logistic regression models, C statistics for diagnosis of sarcopenia (defined as <25th percentile of LBM) were 0.69 for paraspinous muscle area, 0.81 for psoas muscle area, and 0.89 for MTMA. With sarcopenia defined as <10th percentile of LBM, the corresponding C statistics were 0.71, 0.92, and 0.94. CONCLUSIONS: We conclude that psoas muscle area provides a good measure of whole-body muscle mass, better than paraspinous muscle area but slightly inferior to midthigh measurement. Hence, in body composition studies a single axial MR image at the L4-L5 level can be used to provide information on both fat and muscle and may eliminate the need for time consuming measurement of muscle area in the thigh. PMID- 26994782 TI - Fornix and medial temporal lobe lesions lead to comparable deficits in complex visual perception. AB - Recent research dealing with the structures of the medial temporal lobe (MTL) has shifted away from exclusively investigating memory-related processes and has repeatedly incorporated the investigation of complex visual perception. Several studies have demonstrated that higher level visual tasks can recruit structures like the hippocampus and perirhinal cortex in order to successfully perform complex visual discriminations, leading to a perceptual-mnemonic or representational view of the medial temporal lobe. The current study employed a complex visual discrimination paradigm in two patients suffering from brain lesions with differing locations and origin. Both patients, one with extensive medial temporal lobe lesions (VG) and one with a small lesion of the anterior fornix (HJK), were impaired in complex discriminations while showing otherwise mostly intact cognitive functions. The current data confirmed previous results while also extending the perceptual-mnemonic theory of the MTL to the main output structure of the hippocampus, the fornix. PMID- 26994783 TI - Implications of the calf musculature and Achilles tendon architectures for understanding the site of injury. AB - Clinically the sites of Achilles Tendon (AT) overuse conditions can be divided into the tendon mid-portion and osteotendinous attachment. PURPOSE: We propose an anatomical analysis of the triceps surae musculotendon unit that could provide a possible anatomic explanation for these 2 sites of injury. METHOD: Twelve cadavers (age 74+/-7 years) were studied. In both legs, calf muscles (lateral gastrocnemius (LG), medial gastrocnemius (MG) and soleus) were dissected and their volumes measured. Fine saw cuts were made in the sagittal plane, either side of the midline of the calcaneus. Each strip contained the distal part of the tendon and its insertion, together with the superior tuberosity of the calcaneus. Trabecular architecture was analyzed from X-rays taken with Faxitron radiography. Histological sections of the enthesis and the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated. A finite element model of tendon coupled to a rupture index was developed to investigate the AT response to mechanical load. RESULTS: Muscle volume was highest for the soleus, followed by the MG, and LG. Within the AT, the soleus fibers occupy the antero-medial parts, the MG fibers form the posterior lateral layer, yet the LG head fibers retain the antero-lateral part. The quantity of bone and the apparent trabecular thickness at the enthesis were greatest in the central part of the enthesis. Thickness of calcified fibrocartilage tissue was significantly greater in the central part than medially (P=0.04) and laterally (P=0.03). Uncalcified fibrocartilage was significantly thicker medially than laterally (P=0.02). Finally, finite element analysis showed that AT mechanical stress increased with muscle load and converged at 4.6-7.9cm of the enthesis. CONCLUSION: Our data suggest that the triceps surae musculotendon unit is composed of anatomically distinct parts that undergo non-uniform mechanical loading. There are two sites where potentially tendon mechanical stress increases, the medial/central portions of the enthesis and the tendon midportion. PMID- 26994784 TI - Femoral strain during walking predicted with muscle forces from static and dynamic optimization. AB - Mechanical strain plays an important role in skeletal health, and the ability to accurately and noninvasively quantify bone strain in vivo may be used to develop preventive measures that improve bone quality and decrease fracture risk. A non invasive estimation of bone strain requires combined musculoskeletal - finite element modeling, for which the applied muscle forces are usually obtained from static optimization (SO) methods. In this study, we compared finite element predicted femoral strains in walking using muscle forces obtained from SO to those obtained from forward dynamics (FD) simulation. The general trends in strain distributions were similar between FD and SO derived conditions and both agreed well with previously reported in vivo strain gage measurements. On the other hand, differences in peak maximum (epsilonmax) and minimum (epsilonmin) principal strain magnitudes were as high as 32% between FD (epsilonmax/epsilonmin=945/-1271MUepsilon) and SO (epsilonmax/epsilonmin=752/ 859MUepsilon). These large differences in strain magnitudes were observed during the first half of stance, where SO predicted lower gluteal muscle forces and virtually no co-contraction of the hip adductors compared to FD. The importance of these results will likely depend on the purpose/application of the modeling procedure. If the goal is to obtain a generalized strain distribution for adaptive bone remodeling algorithms, then traditional SO is likely sufficient. In cases were strain magnitudes are critical, as is the case with fracture risk assessment, bone strain estimation may benefit by including muscle activation and contractile dynamics in SO, or by using FD when practical. PMID- 26994785 TI - Simulation of effects of botulinum toxin on muscular mechanics in time course of treatment based on adverse extracellular matrix adaptations. AB - BTX effects on muscular mechanics are highly important, but their mechanism and variability in due treatment course is not well understood. Recent modeling shows that partial muscle paralysis per se causes restricted sarcomere shortening due to muscle fiber-extracellular matrix (ECM) mechanical interactions. This leads to two notable acute-BTX effects compared to pre-BTX treatment condition: (1) enhanced potential of active force production of the non-paralyzed muscle parts, and (2) decreased muscle length range of force exertion (lrange). Recent experiments also indicate increased ECM stiffness of BTX treated muscle. Hence, altered muscle fiber-ECM interactions and BTX effects are plausible in due treatment course. Using finite element modeling, the aim was to test the following hypotheses: acute-BTX treatment effects elevate with increased ECM stiffness in the long-term, and are also persistent post-BTX treatment. Model results confirm these hypotheses and show that restricted sarcomere shortening effect becomes more pronounced in the long-term and is persistent or reversed (for longer muscle lengths) post-BTX treatment. Consequently, force production capacity of activated sarcomeres gets further enhanced in the long-term. Remarkably, such enhanced capacity becomes permanent for the entire muscle post treatment. Shift of muscle optimum length to a shorter length is more pronounced in the long-term, some of which remains permanent post-treatment. Compared to Pre BTX treatment, a narrower lrange (20.3%, 27.1% and 3.4%, acute, long-term and post-BTX treatment, respectively) is a consistent finding. We conclude that ECM adaptations can affect muscular mechanics adversely both during spasticity management and post-BTX treatment. Therefore, this issue deserves major future attention. PMID- 26994786 TI - Analysis of dual-task elderly gait in fallers and non-fallers using wearable sensors. AB - Dual-task (DT) gait involves walking while simultaneously performing an attention demanding task and can be used to identify impaired gait or executive function in older adults. Advancment is needed in techniques that quantify the influence of dual tasking to improve predictive and diagnostic potential. This study investigated the viability of wearable sensor measures to identify DT gait changes in older adults and distinguish between elderly fallers and non-fallers. A convenience sample of 100 older individuals (75.5+/-6.7 years; 76 non-fallers, 24 fallers based on 6 month retrospective fall occurrence) walked 7.62m under single-task (ST) and DT conditions while wearing pressure-sensing insoles and tri axial accelerometers at the head, pelvis, and left and right shanks. Differences between ST and DT gait were identified for temporal measures, acceleration descriptive statistics, Fast Fourier Transform (FFT) quartiles, ratio of even to odd harmonics, center of pressure (CoP) stance path coefficient of variation, and deviations to expected CoP stance path. Increased posterior CoP stance path deviations, increased coefficient of variation, decreased FFT quartiles, and decreased ratio of even to odd harmonics suggested increased DT gait variability. Decreased gait velocity and decreased acceleration standard deviations (SD) at the pelvis and shanks could represent compensatory gait strategies that maintain stability. Differences in acceleration between fallers and non-fallers in head posterior SD and pelvis AP ratio of even to odd harmonics during ST, and pelvis vertical maximum Lyapunov exponent during DT gait were identified. Wearable sensor-based DT gait assessments could be used in point-of-care environments to identify gait deficits. PMID- 26994787 TI - Letter to the Editor #2: Description of the Burn Model System National Database sample. PMID- 26994788 TI - Virtual water flows in the international trade of agricultural products of China. AB - With the rapid development of the economy and population, water scarcity and poor water quality caused by water pollution have become increasingly severe in China. Virtual water trade is a useful tool to alleviate water shortage. This paper focuses on a comprehensive study of China's international virtual water flows from agricultural products trade and completes a diachronic analysis from 2001 to 2013. The results show that China was in trade surplus in relation to the virtual water trade of agricultural products. The exported virtual water amounted to 29.94billionm(3)/yr. while 155.55billionm(3)/yr. was embedded in imported products. The trend that China exported virtual water per year was on the decline while the imported was on a rising trend. Virtual water trade of China was highly concentrated. Not all of the exported products had comparative advantages in virtual water content. Imported products were excessively concentrated on water intensive agricultural products such as soya beans, cotton, and palm oil. The exported virtual water mainly flowed to the Republic of Korea, Hong Kong of China and Japan, while the imported mainly flowed from the United States of America, Brazil and Argentina. From the ethical point of view, the trade partners were classified into four types in terms of "net import" and "water abundance": mutual benefit countries, such as Australia and Canada; unilateral benefit countries, such as Mongolia and Norway; supported countries, such as Egypt and Singapore; and double pressure countries, such as India and Pakistan. Virtual water strategy refers to water resources, agricultural products and human beings. The findings are beneficial for innovating water resources management system, adjusting trade structure, ensuring food security in China, and promoting the construction of national ecological security system. PMID- 26994789 TI - High field FT-ICR mass spectrometry for molecular characterization of snow board from Moscow regions. AB - High field Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry analysis of eight snow samples from Moscow city allowed us to identify more than 2000 various elemental compositions corresponding to regional air pollutants. The hierarchical cluster analysis (HCA) of the data showed good concordance of three main groups of samples with the main wind directions. The North-West group (A1) is represented by several homologous CHOS series of aliphatic organic aerosols. They may form as a result of enhanced photochemical reactions including oxidation of hydrocarbons with sulfonations due to higher amount of SO2 emissions in the atmosphere in this region. Group A2, corresponding to the South-East part of Moscow, contains large amount of oxidized hydrocarbons of different sources that may form during oxidation in atmosphere. These hydrocarbons appear correlated to emissions from traffic, neighboring oil refinery, and power plants. Another family of compounds specific for this region involves CHNO substances formed during oxidation processes including NOx and NO3 radical since emissions of NOx are higher in this part of the city. Group A3 is rich in CHO type of compounds with high H/C and low O/C ratios, which is characteristic of oxidized hydrocarbon like organic aerosol. CHNO types of compounds in A3 group are probably nitro derivatives of condensed hydrocarbons such as PAH. This non-targeted profiling revealed site specific distribution of pollutants and gives a chance to develop new strategies in air quality control and further studies of Moscow environment. PMID- 26994790 TI - Can analysis of Platichthys flesus otoliths provide relevant data on historical metal pollution in estuaries? Experimental and in situ approaches. AB - Despite recent efforts to manage them more efficiently, estuaries are natural sinks for a wide range of metal contaminants, many of which accumulate at potentially toxic concentrations for fish populations, posing a threat to recruitment and stocks. While analysis of metal concentrations in soft tissue and water samples calls for continuous and long-term sampling operations, the use of otoliths to study metal pollution may be one way of providing a historical record of pollutant exposure. In this study, we examine the potential use of otoliths as natural tracers of metal contamination. A "cocktail" of different metals (Cd, Pb and Ni) was used to test bio-accumulation in otoliths and tissue (liver, kidney, muscle and gills) extracted from juvenile flounder (Platichthys flesus). Assessment took place under controlled conditions over a three month period, with water exposure concentrations increasing every 3weeks. The concentrations used were natural (T1), X5 (T2), X10 (T3), and null (T4). Chemical analyses were carried out using an inductively coupled plasma optical emission spectrometer ICP OES and atomic absorption spectrometer AAS for water and tissue, while otolith microchemistry analyses were performed using a femtosecond laser ablation-high resolution inductively coupled plasma mass spectrometer (fsLA-ICP-MS-HR). Significant differences between control and exposed individuals, as well as an increase in metal concentrations according to exposure level, were observed in all tissues except in muscle tissue. Significant increases in Pb were also detected in contaminated fish otoliths compared with control specimens, with the highest concentrations occurring in T3. Cartographies of Pb distribution in otoliths of both control and contaminated fish only showed high concentrations of Pb at the edge of contaminated fish otoliths, indicating an accumulation of metal during the experiment. Although the relationships between exposure level and Pb concentration in otoliths were complex, the concentrations were correlated with those in the water. Analysis of flounder specimens collected from 2007 to 2014 in the Gironde estuary (SW France) showed interannual variability in Pb concentrations, with higher values for fish otoliths from 2007 to 2010 than those from 2012 to 2014. This trend indicated a decrease in Pb in the Gironde estuary over the last decade, which is consistent with the results of other surveys on bivalves. Our study demonstrates that it is possible to use otolith microchemistry as a tool in assessing and retracing long-term metal pollution in estuarine systems. PMID- 26994791 TI - Environmental risk analysis and prioritization of pharmaceuticals in a developing world context. AB - The impact of residual pharmaceuticals on the aquatic environment has gained widespread attention over the past years. Various studies have established the occurrence of pharmaceutical compounds in different water bodies throughout the world. In view of the absence of occurrence data in a number of developing world countries, and given the limited availability of analytical resources in these countries, it is prudent to devise methodologies to prioritize pharmaceuticals for environmental monitoring purposes that are site specific. In this work, several prioritization approaches are used to rank the 88 most commonly consumed pharmaceuticals in Lebanon. A simultaneous multi-criteria decision analysis method utilizing the exposure, persistence, bioaccumulation, and toxicity (EPBT) approach is applied to a smaller subset of the original list (69 pharmaceuticals). Several base cases are investigated and sensitivity analysis is applied to one of these base case runs. The similarities and differences in the overall ranking of individual, and classes of, pharmaceuticals for the base cases and the sensitivity runs are elucidated. An environmental risk assessment (ERA), where predicted environmental concentrations (PEC) and risk quotients (RQ) are determined at different dilution factors, is performed as an alternative method of prioritization for a total of 84 pharmaceuticals. The ERA results indicate that metformin and amoxicillin have the highest PECs while 17beta-estradiol, naftidrofuryl and dimenhydrinate have the highest RQs. The two approaches, EPBT prioritization and ERA, are compared and a priority list consisting of 26 pharmaceuticals of various classes is developed. Nervous system and alimentary tract and metabolism pharmaceuticals (9/26 and 5/26 respectively) constitute more than half of the numbers on the priority list with the balance consisting of anti infective (4/26), musculo-skeletal (3/26), genito-urinary (2/26), respiratory (2/26) and cardiovascular (1/26) pharmaceuticals. This list will serve as a basis for the selection of candidate compounds to focus on for future monitoring campaigns. PMID- 26994792 TI - Exploring high charge of phosphate as new draw solute in a forward osmosis membrane distillation hybrid system for concentrating high-nutrient sludge. AB - For the first time, a high charge of phosphate was used as the draw solute in a forward osmosis-membrane distillation (FO-MD) hybrid system for concentrating high-nutrient sludge. A high water flux (12.5L/m(2)h) and a low reverse salt flux (0.84g/m(2)) were simultaneously achieved at pH9 by using 0.1M Na3PO4 as the draw solute and deionized water as the feed solution in the FO process. The specific reverse salt flux of 0.1M Na3PO4 (Js/Jw=0.07g/L) was considerably less than that of 0.1M NaCl (Js/Jw=0.37g/L) because the complexion between Na(+) and HPO4(2-) at pH9 led to the reduction of free Na(+) ions, which subsequently reduced the reverse salt diffusion substantially. Moreover, for a feed solution with an initial sludge concentration of 3500mg/L, the sludge concentration could be concentrated to 19,800 and 22,000mg/L in the pressure-retarded osmosis (PRO) and FO membrane orientations, respectively, after 15h of operation. Four types of MD membranes were selected for draw solution recovery; of these, a polytetrafluoroethylene membrane with a pore size of 0.45MUm was the most effective in achieving a high water flux (10.28L/m(2)h) and high salt rejection (approximately 100%) in a diluted Na3PO4 draw solution. PMID- 26994793 TI - Boreal forests can have a remarkable role in reducing greenhouse gas emissions locally: Land use-related and anthropogenic greenhouse gas emissions and sinks at the municipal level. AB - Ecosystem services have become an important concept in policy-making. Carbon (C) sequestration into ecosystems is a significant ecosystem service, whereas C losses can be considered as an ecosystem disservice. Municipalities are in a position to make decisions that affect local emissions and therefore are important when considering greenhouse gas (GHG) mitigation. Integrated estimations of fluxes at a regional level help local authorities to develop land use policies for minimising GHG emissions and maximising C sinks. In this study, the Finnish national GHG accounting system is modified and applied at the municipal level by combining emissions and sinks from agricultural land, forest areas, water bodies and mires (land use-related GHG emissions) with emissions from activities such as energy production and traffic (anthropogenic GHG emissions) into the LUONNIKAS calculation tool. The study area consists of 14 municipalities within the Vanajavesi catchment area located in Southern Finland. In these municipalities, croplands, peat extraction sites, water bodies and undrained mires are emission sources, whereas forests are large carbon sinks that turn the land use-related GHG budget negative, resulting in C sequestration into the ecosystem. The annual land use-related sink in the study area was 78tCO2eqkm( 2) and 2.8tCO2eq per capita. Annual anthropogenic GHG emissions from the area amounted to 250tCO2eqkm(-2) and 9.2tCO2eq per capita. Since forests are a significant carbon sink and the efficiency of this sink is heavily affected by forest management practices, forest management policy is a key contributing factor for mitigating municipal GHG emissions. PMID- 26994794 TI - Bioaccumulation and bioconcentration of carbamazepine and other pharmaceuticals in fish under field and controlled laboratory experiments. Evidences of carbamazepine metabolization by fish. AB - There is a growing interest in evaluating the presence of pharmaceutical residues and their metabolites in aquatic biota. In this study, twenty pharmaceuticals, including carbamazepine (CBZ) and two metabolites, were analyzed in homogenates of two fish species (Gambusia affinis and Jenynsia multidentata) captured in polluted areas of the Suquia River (Cordoba, Argentina). The twenty target pharmaceuticals were found in G. affinis, while only fifteen were detected in J. multidentata. We observed a noticeable difference in the accumulation pattern of both fish species, suggesting different pathways for the bioaccumulation of polar pharmaceuticals in each fish. In order to investigate uptake and tissue distribution of pharmaceuticals, a detailed study was performed under controlled laboratory conditions in J. multidentata, exposed to CBZ. CBZ and two of its metabolites (carbamazepine-10,11-epoxide - CBZ-EP and 2-hydroxycarbamazepine - 2 OH-CBZ) were monitored in five organs of fish under laboratory exposure. To our knowledge, this is the first report on the presence of CBZ and its metabolite 2 OH-CBZ in gills, intestine, liver, brain and muscle of fish, while the metabolite carbamazepine-10,11-epoxide (CBZ-EP) was detected in gills and muscle. A ratio CBZ-EP/CBZ close to 0.1 suggests that gills and muscle of J. multidentata could metabolize CBZ through the CBZ-EP pathway. Our results reinforce the need of analyzing multiple species to account for the environmental impact of pollutants, negating the simplification of a single, "representative model" during ecotoxicological biomonitoring. To our knowledge, the biotransformation of CBZ to its metabolites (CBZ-EP, 2-OH-CBZ) in fish, under controlled laboratory in vivo exposures, is reported for the first time. PMID- 26994795 TI - Occurrence, spatiotemporal distribution, and ecological risks of steroids in a large shallow Chinese lake, Lake Taihu. AB - Steroids have been frequently detected in surface waters, and might pose adverse effects on aquatic organisms. However, little information is available regarding the occurrence and spatiotemporal distribution of steroids in lake environments. In addition to pollution sources, the occurrence and spatiotemporal distribution of steroids in lake environments might be related to lake types (shallow or deep), lake hydrodynamics, and sorption-desorption processes in the water sediment systems. In this study, the occurrence, spatiotemporal distribution, and ecological risks of 36 steroids in a large shallow lake were evaluated by investigating surface water and sediment samples at 32 sites in Lake Taihu over two seasons. Twelve and 15 analytes were detected in aqueous and sedimentary phases, respectively, with total concentrations ranging from 0.86 to 116ng/L (water) and from 0.82 to 16.2ng/g (sediment, dry weight). Temporal variations of steroid concentrations in the water and sediments were statistically significant, with higher concentrations in winter. High concentrations of steroids were found in the seriously polluted bays rather than in the pelagic zone of the lake. Strong lake currents might mix pelagic waters, resulting in similar concentrations of steroids in the pelagic zone. Mass balance analysis showed that sediments in shallow lakes are in general an important sink for steroids. Steroids in the surface water and sediments of Lake Taihu might pose potential risks to aquatic organisms. Overall, our study indicated that the concentrations and spatiotemporal distribution of steroids in the large shallow lake are influenced simultaneously by pollution sources and lake hydrodynamics. CAPSULE: Steroids in the large shallow Lake Taihu showed clear temporal and spatial variations and lake sediments may be a potential sink of steroids. PMID- 26994797 TI - Abrupt state change of river water quality (turbidity): Effect of extreme rainfalls and typhoons. AB - River turbidity is of dynamic nature, and its stable state is significantly changed during the period of heavy rainfall events. The frequent occurrence of typhoons in Taiwan has caused serious problems in drinking water treatment due to extremely high turbidity. The aim of the present study is to evaluate impact of typhoons on river turbidity. The statistical methods used included analyses of paired annual mean and standard deviation, frequency distribution, and moving standard deviation, skewness, and autocorrelation; all clearly indicating significant state changes of river turbidity. Typhoon Morakot of 2009 (recorded high rainfall over 2000mm in three days, responsible for significant disaster in southern Taiwan) is assumed as a major initiated event leading to critical state change. In addition, increasing rate of turbidity in rainfall events is highly and positively correlated with rainfall intensity both for pre- and post-Morakot periods. Daily turbidity is also well correlated with daily flow rate for all the eleven events evaluated. That implies potential prediction of river turbidity by river flow rate during rainfall and typhoon events. Based on analysis of stable state changes, more effective regulations for better basin management including soil-water conservation in watershed are necessary. Furthermore, municipal and industrial water treatment plants need to prepare and ensure the adequate operation of water treatment with high raw water turbidity (e.g., >2000NTU). Finally, methodology used in the present of this study can be applied to other environmental problems with abrupt state changes. PMID- 26994796 TI - Evaluating management tradeoffs between economic fiber production and other ecosystem services in a Chinese-fir dominated forest plantation in Fujian Province. AB - Chinese fir (Cunninghamia lanceolata) is not only a valuable timber species, but also plays an important role in the provision of ecosystem services. Forest management decisions to increase the production of fiber for economic gain may have negative impacts on the long-term flow of ecosystem services from forest resources. Such tradeoffs should be taken into account to fulfill the requirements of sustainable forest management. Here we employed an established, ecosystem-based, stand-level model (FORECAST) in combination with a simplified harvest-scheduling model to evaluate the potential tradeoffs among indicators of provisional, regulating and supporting ecosystem services in a Chinese-fir dominated landscape located in Fujian Province as a case study. Indicators included: merchantable volume harvested, biomass harvested, ecosystem carbon storage, CO2 fixation, O2 released, biomass nitrogen content, pollutant absorption, and soil fertility. A series of alternative management scenarios, representing different combinations of rotation length and harvest intensity, were simulated to facilitate the analysis. Results from the analysis were summarized in the form of a decision matrix designed to provide a method for forest managers to evaluate management alternatives and tradeoffs in the context of key indicators of ecosystem services. The scenario analysis suggests that there are considerable tradeoffs in terms of ecosystem services associated with stand and landscape-level management decisions. Longer rotations and increased retention tended to favor regulating and supporting services while the opposite was true for provisional services. PMID- 26994798 TI - Impact of extreme metal contamination at the supra-individual level in a contaminated bay ecosystem. AB - Anthropogenic stressors impact the global environment and adversely affect the health of organisms and humans. This study was designed as an attempt to evaluate the ecological consequences of severe metal contamination at the supra-individual level based on a field investigation in Jinzhou Bay (JZB), North China in 2010. The chemical results showed high concentrations of metals in the sediment of JZB that were ~129 times greater than the local geochemical background. Furthermore, the measured metals exhibited considerably high toxicity potential indicated by sediment quality guidelines (SQGs). The mean SQGs quotients suggested the overall toxicity incidence was >70% in locations neighboring the Wulihe River mouth. Biomonitoring revealed 116 individuals distributed among a mere 6 species, 4 of which were polychaetes, at 33% of the sampling sites. Thus, few benthic organisms were present in the damaged community structures across the region, which was consistent with the extreme metal contamination. Moreover, the sediment quality assessment, in a weight of evidence framework, demonstrated that the sediment throughout the entire JZB was moderately to severely impaired, especially in the vicinity of the Wulihe River mouth. By synthesizing the present and previous chemical-biological monitoring campaigns, a possible cause-effect relationship between chemical stressors and benthic receptors was established. We also found that the hydrodynamics, sediment sources, and geochemical characteristics of the metals (in addition to the sources of the metals) were responsible for the geochemical distribution of metals in JZB. The significance of the overall finding is that the deleterious responses observed at the community level may possibly be linked to the extreme chemical stress in the sediment of JZB. PMID- 26994799 TI - Railway cuttings and embankments: Experimental and numerical studies of ground vibration. AB - Railway track support conditions affect ground-borne vibration generation and propagation. Therefore this paper presents a combined experimental and numerical study into high speed rail vibrations for tracks on three types of support: a cutting, an embankment and an at grade section. Firstly, an experimental campaign is undertaken where vibrations and in-situ soil properties are measured at three Belgian rail sites. A finite element model is then developed to recreate the complex ground topology at each site. A validation is performed and it is found that although the at-grade and embankment cases show a correlation with the experimental results, the cutting case is more challenging to replicate. Despite this, each site is then analysed to determine the effect of earthworks profile on ground vibrations, with both the near and far fields being investigated. It is found that different earthwork profiles generate strongly differing ground-borne vibration characteristics, with the embankment profile generating lower vibration levels in comparison to the cutting and at-grade cases. Therefore it is concluded that it is important to consider earthwork profiles when undertaking vibration assessments. PMID- 26994800 TI - Using biomarkers as fingerprint properties to identify sediment sources in a small catchment. AB - Traditional fingerprinting methods are limited in their ability to identify soil erosion sources where geologic variations are small or where different land uses span geological boundaries. In this study, a new biomarker for fingerprinting, specifically, n-alkanes, was used in a small catchment to identify sediment sources. The n-alkanes were based on land uses, could provide vegetation information, and were relatively resistant to diagenetic modifications and decomposition. This study used a composite fingerprinting method that was based on two types of fingerprint factors (27 biomarker properties and 45 geochemical properties) with 60 source samples (i.e., gully, grassland, forest, and cropland) and nine soil profiles. Genetic algorithm (GA) optimization has been deployed to find the optimal source contribution to sediments. The biomarker results demonstrated that young forest is the main sediment source in this catchment, contributing 50.5%, whereas cropland, grassland and gully contributed 25.6%, 14.4% and 9.5%, respectively; the geochemistry results were similar to the biomarkers. The forest and grassland contributions gradually increased from upstream to downstream, and the sediment contributions of cropland gradually decreased in the direction of the runoff pathway at the check dam. In a comparison of biomarker and geochemical fingerprinting data, the latter may have overestimated the forest inputs to the catchment sediment yields because of a mixed land use history (i.e., forest and grassland). The geochemical fingerprint approach limits its ability to fully discriminate sources based on land management regimes, but the biomarker (individual n-alkanes) displayed the potential to discriminate between a greater number and different types of sediment sources and to provide greater detail regarding sediment sources. PMID- 26994801 TI - What are the core ideas behind the Precautionary Principle? AB - The Precautionary Principle is both celebrated and criticized. It has become an important principle for decision making, but it is also subject to criticism. One problem that is often pointed out with the principle is that is not clear what it actually says and how to use it. I have taken on this problem by performing an analysis of some of the most influential formulations of the principle in an attempt to identify the core ideas behind it, with the purpose of producing a formulation of the principle that is clear and practically applicable. It was found that what is called the Precautionary Principle is not a principle that tells us what do to achieve extra precaution or how to handle situations when extra precaution is called for. Instead, it was found to be a list of circumstances that each justify extra precaution. An analysis of some of the most common and influential formulations of the Precautionary Principle identified four such circumstances: (1) When we deal with important values that tend to be systematically downplayed by traditional decision methods - such as human health and the environment. (2) When we suspect that the decision might lead to irreversible and severe consequences and the values at stake are also irreplaceable, (3) When timing is at least as important as being right. (4) When it is more important to avoid false negatives than false positives. This interpretation of the Precautionary Principle does not say anything about what kind of actions to take when extra precaution is called for, but it does provide a clear and practically useful list of circumstances that call for extra precaution and that is not subject to the most common objections to the Precautionary Principle. PMID- 26994802 TI - Debris-flow risk analysis in a managed torrent based on a stochastic life-cycle performance. AB - Two key factors can affect the functional ability of protection structures in mountains torrents, namely (i) infrastructure maintenance of existing infrastructures (as a majority of existing works is in the second half of their life cycle), and (ii) changes in debris-flow activity as a result of ongoing and expected future climatic changes. Here, we explore the applicability of a stochastic life-cycle performance to assess debris-flow risk in the heavily managed Wartschenbach torrent (Lienz region, Austria) and to quantify associated, expected economic losses. We do so by considering maintenance costs to restore infrastructure in the aftermath of debris-flow events as well as by assessing the probability of check dam failure (e.g., as a result of overload). Our analysis comprises two different management strategies as well as three scenarios defining future changes in debris-flow activity resulting from climatic changes. At the study site, an average debris-flow frequency of 21 events per decade was observed for the period 1950-2000; activity at the site is projected to change by +38% to 33%, according to the climate scenario used. Comparison of the different management alternatives suggests that the current mitigation strategy will allow to reduce expected damage to infrastructure and population almost fully (89%). However, to guarantee a comparable level of safety, maintenance costs is expected to increase by 57-63%, with an increase of maintenance costs by ca. 50% for each intervention. Our analysis therefore also highlights the importance of taking maintenance costs into account for risk assessments realized in managed torrent systems, as they result both from progressive and event-related deteriorations. We conclude that the stochastic life-cycle performance adopted in this study represents indeed an integrated approach to assess the long-term effects and costs of prevention structures in managed torrents. PMID- 26994803 TI - Copper in soil fractions and runoff in a vineyard catchment: Insights from copper stable isotopes. AB - Understanding the fate of copper (Cu) fungicides in vineyard soils and catchments is a prerequisite to limit the off-site impact of Cu. Using Cu stable isotopes, Cu retention in soils and runoff transport was investigated in relation to the use of Cu fungicides and the hydrological conditions in a vineyard catchment (Rouffach, Haut-Rhin, France; mean slope: 15%). The delta(65)Cu values of the bulk vineyard soil varied moderately through the depth of the soil profiles ( 0.12 to 0.240/00+/-0.080/00). The values were in the range of those of the fungicides (-0.21 to 0.110/00) and included the geogenic delta(65)Cu value of the untreated soil (0.080/00). However, delta(65)Cu values significantly differed between particle-size soil fractions (-0.37+/-0.100/00 in fine clays and 0.23+/ 0.070/00 in silt). Together with the soil mineralogy, the results suggested Cu isotope fractionation primarily associated with the clay and fine clay fractions that include both SOM and mineral phases. The vegetation did not affect the Cu isotope patterns in the vineyard soils. Cu export by runoff from the catchment accounted for 1% of the applied Cu mass from 11th May to 20(th) July 2011, covering most of the Cu use period. 84% of the exported Cu mass was Cu bound to suspended particulate matter (SPM). The runoff displayed delta(65)Cu values from 0.52 to 1.350/00 in the dissolved phase (<0.45MUm) compared to -0.34 to -0.020/00 in the SPM phase, indicating that clay and fine clay fractions were the main vectors of SPM-bound Cu in runoff. Overall, this study shows that Cu stable isotopes may allow identifying the Cu distribution in the soil fractions and their contribution to Cu export in runoff from Cu-contaminated catchments. PMID- 26994804 TI - Health effects from low-frequency noise and infrasound in the general population: Is it time to listen? A systematic review of observational studies. AB - A systematic review of observational studies was conducted to assess the association between everyday life low-frequency noise (LFN) components, including infrasound and health effects in the general population. Literature databases Pubmed, Embase and PsycInfo and additional bibliographic sources such as reference sections of key publications and journal databases were searched for peer-reviewed studies published from 2000 to 2015. Seven studies met the inclusion criteria. Most of them examined subjective annoyance as primary outcome. The adequacy of provided information in the included papers and methodological quality of studies was also addressed. Moreover, studies were screened for meta-analysis eligibility. Some associations were observed between exposure to LFN and annoyance, sleep-related problems, concentration difficulties and headache in the adult population living in the vicinity of a range of LFN sources. However, evidence, especially in relation to chronic medical conditions, was very limited. The estimated pooled prevalence of high subjective annoyance attributed to LFN was about 10%. Epidemiological research on LFN and health effects is scarce and suffers from methodological shortcomings. Low frequency noise in the everyday environment constitutes an issue that requires more research attention, particularly for people living in the vicinity of relevant sources. PMID- 26994805 TI - Transcriptional profiling induced by pesticides employed in organic agriculture in a wild population of Chironomus riparius under laboratory conditions. AB - Copper (Cu) and azadirachtin (AZA-A+B) are pesticides allowed in organic agriculture whose environmental risk and toxicity for aquatic wildlife is only partially known. Reverse Transcription Polymerase Chain Reaction was used to assess the molecular effect of acute and short-term exposure (3, 24h) of Cu (0.01, 0.05, 1, 10, 25mgl(-1)) and AZA-A+B (0.2, 0.3, 0.4, 0.5, 1mgl(-1)) on the expression of five candidate genes (hsp70, hsc70, hsp40, hsp10 and cyP450) in a non-target species, Chironomus riparius. Fourth-instar larvae were collected from a mountain stream polluted by agricultural land run-off. All genes were responsive to both pesticides but each gene had a specific response to the different experimental concentrations and exposure times. A few similarities in transcriptional profiling were observed, such as a linear concentration-dependent response of hsp70 after 24h of exposure (at >=1mgl(-1) of Cu and >=0.2mgl(-1) of AZA-A+B) and an up-regulation regardless of the concentration of hsc70 after 24h of exposure (at >=0mgl(-1) of Cu and >=0.2mgl(-1) of AZA-A+B and the up regulation of hsp70 after 3h of exposure at ~LC50 (Cu-LC50=26.1+/-2.5mgl(-1), AZA A+B-LC50=1.1+/-0.2mgl(-1)). According to the results, hsp40, hsp10 and cyP450 may be defined as pesticide-dependent (i.e., hsp40 and hsp10 seemed to responded mainly to AZA-A+B and cyP450 to Cu), while hsc70 as time-dependent regardless of the pesticide (i.e., hsc70 responded only after 24h of treatment with Cu and AZA A+B). This study gives new insights on the potential role of the C. riparius's hsps and cyP450 genes as sensitive biomarkers for freshwater monitoring. PMID- 26994806 TI - Mobility and attenuation of arsenic in sulfide-rich mining wastes from the Czech Republic. AB - The mineralogical composition of mining wastes deposited in countless dumps around the world is the key factor that controls retention and release of pollutants. Here we report a multi-method data set combining mineralogical (X-ray diffraction, electron microprobe and Raman microspectrometry) and geochemical (sequential extraction and pore water analysis) methods to resolve As mobility in two 50-years-old mining waste dumps. Originally, all of the As in the mining wastes selected for the study was present as arsenopyrite and with time it has been replaced by secondary As phases. At Jedova jama mining area, the most of As precipitated as X-ray amorphous ferric arsenate (HFA). Arsenic is also accumulated in the scorodite and Fe (hydr)oxide (with up to 3.2wt.% As2O5) that is particularly represented by hematite. Mining wastes at Dlouha Ves contain only trace amount of scorodite. Arsenic is primarily bound to Pb-jarosite and Fe (hydr)oxides (especially goethite) with up to 1.6 and 1.8wt.% As2O5, respectively. The pore water collected after rainfall events indicated high concentrations of As (~4600MUg.L(-1)) at Jedova jama, whereas aqueous As at Dlouha Ves was negligible (up to 1.5MUg.L(-1)). Highly mobile As at Jedova jama is attributed to the dissolution of HFA and simultaneous precipitation of Fe (hydr)oxides under mildly acidic conditions (pH~4.4); immobile As at Dlouha Ves is due to the efficient adsorption on the Fe (hydr)oxides and hydroxosulfates under acidic pH of ~2.8. Taken together, As mobility in the ferric arsenates containing mining wastes may significantly vary. These wastes must be kept under acidic conditions or with high aqueous Fe(III) concentrations to prevent the release of As from incongruent dissolution of ferric arsenates. PMID- 26994808 TI - Field application of selective precipitation for recovering Cu and Zn in drainage discharged from an operating mine. AB - Acid mine drainage (AMD) generated from mining activities has been recognized as a serious problem due to its increased acidity and high concentration of heavy metals. In this research, a feasibility test of the selective precipitation (SP) process was performed using AMD discharged from a currently operating mine in Korea for the purpose of minimizing the environmental impact of AMD. For the SP process, a pilot scale equipment (100L reaction tank) was used in field and among various metals, Cu and Zn were the target metals. Through the research, it was confirmed that AMD from an operating mine has two disadvantages of being applied to the SP: altering water quality and unexpected inclusion of clay debris. Despite unfavorable conditions, Cu and Zn precipitate of 80% purity with 90% precipitation rate was able to be obtained from 1.4L/min (2.0tons/day) AMD. The recovered precipitates were identified as amorphous CuS and ZnS with small amounts of impurities (Si minerals, CuFeS2, and Fe/Al hydroxide). The strategies to reduce these impurities were also discussed. Recovery rate, which is the amount of precipitate collected per unit volume of AMD, was proposed as an indicator to evaluate the working efficiency of the SP process. It was confirmed that the recovery rate was strongly dependent on flow rate and dose of coagulant. The results of this study may be helpful in reducing the potential complications which occurs when SP is applied on field. PMID- 26994807 TI - Diploid and triploid African catfish (Clarias gariepinus) differ in biomarker responses to the pesticide chlorpyrifos. AB - The impacts of environmental stressors on polyploid organisms are largely unknown. This study investigated changes in morphometric, molecular, and biochemical parameters in full-sibling diploid and triploid African catfish (Clarias gariepinus) in response to chlorpyrifos (CPF) exposures. Juvenile fish were exposed to three concentrations of CPF (mean measured MUg/L (SD): 9.71 (2.27), 15.7 (3.69), 31.21 (5.04)) under a static-renewal condition for 21days. Diploid control groups had higher hepatosomatic index (HSI), plasma testosterone (T), and brain GnRH and cyp19a2 expression levels than triploids. In CPF-exposed groups, changes in HSI, total weight and length were different between the diploid and triploid fish. In contrast, condition factor did not alter in any of the treatments, while visceral-somatic index (VSI) changed only in diploids. In diploid fish, exposure to CPF did not change brain 11beta-hsd2, ftz-f1, foxl2, GnRH or cyp19a2 mRNA levels, while reduced tph2 transcript levels compared to the control group. In contrast, 11beta-hsd2 and foxl2 expression levels were changed in triploids following CPF exposures. In diploids, plasma T levels showed a linear dose-response reduction across CPF treatments correlating with liver weight and plasma total cholesterol concentrations. In contrast, no changes in plasma cholesterol and T concentrations were observed in triploids. Plasma cortisol and 17-beta estradiol (E2) showed no response to CPF exposure in either ploidy. Results of this first comparison of biomarker responses to pesticide exposure in diploid and polyploid animals showed substantial differences between diploid and triploid C. gariepinus. PMID- 26994809 TI - Trends and variability in the levels of urinary thiocyanate, perchlorate, and nitrate by age, gender, race/ethnicity, smoking status, and exposure to environmental tobacco smoke over 2005-2012. AB - Data from National Health and Nutrition Examination Survey for 2005-2012 were used to study the trends and variability in the levels of urinary thiocyanate (u SCN), perchlorate (u-P8), and nitrate (u-NO3) by gender, race/ethnicity, active smoking, and exposure to environmental tobacco smoke (ETS) at home for those aged 12-19 and >=20years old. For those aged >=20years, adjusted levels of u-SCN, u P8, and u-NO3 (i) were lower for males than females (p<0.01), and (ii) were higher for non-Hispanic white (NHW) than non-Hispanic black (NHB) (p<0.01). Also, for those aged >=20years NHB had higher adjusted levels than Mexican American (MA) for u-SCN (p<0.01) but NHB had lower adjusted levels than MA for u-P8 (p<0.01) and u-NO3 (p<0.01). For those aged 12-19years, adjusted levels of u-SCN, u-P8, and u-NO3 did not vary by gender (p>0.05), and adjusted levels of u-P8 and u-NO3 for NHB were lower than for NHW (p<0.01) as well as higher for NHB than MA for u-SCN (p<0.01) and lower for NHB than MA (p<0.01) for u-P8 and u-NO3. Among those aged >=20years, active smoking was associated with higher adjusted levels of u-SCN (p<0.01) in a dose-response manner and active smoking was associated with lower adjusted levels of u-P8 (p<0.01) in a dose-response manner. Exposure to ETS was associated with higher adjusted levels of u-SCN (p=0.02) and lower adjusted levels of u-P8 (p<0.01) among >=20years old. Adjusted levels of u-P8 decreased over 2005-2012 among both 12-19 (p<0.01) and >=20years old (p=0.04). There was borderline increase in the adjusted levels of u-NO3 for those aged >=20years (p=0.05) over 2005-2012. PMID- 26994810 TI - Effects of long term rice straw application on the microbial communities of rapeseed rhizosphere in a paddy-upland rotation system. AB - The influence of the rice straw application on rhizosphere microbial communities in the long-term rotation system remains unclear. Two experimental sites (Jingzhou and Wuxue) with the same straw fertilization have been cultivated under the rapeseed-rice rotation mode for 7years. Eco-plate data indicated that the microbial metabolic potential at both sites was enhanced in the cores applied with rice straw. Rhizosphere microbial communities at the two fields could be well distinguished by phospholipid fatty acid data. Redundancy analysis showed that the rapeseed rhizosphere microbial communities in Jingzhou were influenced by soil moisture content, available potassium and available nitrogen, whereas those in Wuxue were influenced by soil available phosphorous, available potassium, total soil carbon and available nitrogen. Variation in soil enzyme activities could be mainly explained by available potassium in Jingzhou, and it was significantly affected by total soil carbon, available nitrogen, available potassium, available phosphorous, total soil nitrogen, moisture content and total phosphorous in Wuxue. The two rapeseed rhizosphere microbial communities are differently affected by the rice-straw application. Rhizosphere with more fungi was passively influenced by the rice-straw, while that with more Gram-negative bacteria was actively in response to the treatment. PMID- 26994811 TI - Ultraviolet filters differentially impact the expression of key endocrine and stress genes in embryos and larvae of Chironomus riparius. AB - Several organic UV filters have hormonal activity in vertebrates, as demonstrated in fishes, rodents and human cells. Despite the accumulation of filter contaminants in aquatic systems, research on their effects on the endocrine systems of freshwaters invertebrates is scarce. In this work, the effects of five frequently used UV filters were investigated in embryos and larvae of Chironomus riparius, which is a reference organism in ecotoxicology. LC50 values for larvae as well as the percentage of eclosion of eggs were determined following exposures to: octyl-p-methoxycinnamate (OMC) also known as 2-ethylhexyl-4-methoxycinnamate (EHMC); 4-methylbenzylidene camphor (4MBC); 4-hydroxybenzophenone (4HB); octocrylene (OC); and octyldimethyl-p-aminobenzoate (OD-PABA). To assess sublethal effects, expression levels of the genes coding for the ecdysone receptor (EcR) and heat shock protein HSP70 were investigated as biomarkers for endocrine and stress effects at the cellular level. Life-stage-dependent sensitivity was found. In embryos, all of the UV filters provoked a significant overexpression of EcR at 24h after exposure. OC, 4MBC and OD-PABA also triggered transcriptional activation of the hsp70 stress gene in embryos. In contrast, in larvae, only 4MBC and OMC/EHMC increased EcR and hsp70 mRNA levels and OD-PABA upregulated only the EcR gene. These results revealed that embryos are particularly sensitive to UV filters, which affect endocrine regulation during development. Most UV filters also triggered the cellular stress response, and thus exhibit proteotoxic effects. The differences observed between embryos and larvae and the higher sensitivity of embryos highlight the importance of considering different life stages when evaluating the environmental risks of pollutants, particularly when analyzing endocrine effects. PMID- 26994812 TI - Modeling electron transfer in photosystem I. AB - Nanosecond to millisecond time-resolved absorption spectroscopy has been used to study electron transfer processes in photosystem I particles from Synechocystis sp. PCC 6803 with eight different quinones incorporated into the A1 binding site, at both 298 and 77K. A detailed kinetic model was constructed and solved within the context of Marcus electron transfer theory, and it was found that all of the data could be well described only if the in situ midpoint potentials of the quinones fell in a tightly defined range. For photosystem I with phylloquinone incorporated into the A1 binding site all of the time-resolved optical data is best modeled when the in situ midpoint potential of phylloquinone on the A/B branch is -635/-690 mV, respectively. With the midpoint potential of the F(X) iron sulfur cluster set at -680 mV, this indicates that forward electron transfer from A(1)(-) to F(X) is slightly endergonic/exergonic on the A/B branch, respectively. Additionally, for forward electron transfer from A(1)(-) to F(X), on both the A and B branches the reorganization energy is close to 0.7 eV. Reorganization energies of 0.4 or 1.0 eV are not possible. For the eight different quinones incorporated, the same kinetic model was used, allowing us to establish in situ redox potentials for all of the incorporated quinones on both branches. A linear correlation was found between the in situ and in vitro midpoint potentials of the quinones on both branches. PMID- 26994813 TI - Predictive factors of bacterial meningitis in the patients seen in emergency departments. AB - OBJETIVES: To analyse and compare predictive factors of bacterial meningitis in the patients seen in the Emergency Departments (ED) due to an episode of acute meningitis (AM). METHODS: A prospective, observational study was carried out in patients aged 15 years and older seen in ED due to AM between August 2009 and November 2015. Thirty-two variables for predicting bacterial meningitis were assessed. They covered epidemiological, comorbidity, clinical and analytical factors. Multivariate logistic regression analysis was performed. RESULTS: The study included 154 patients. The diagnosis was bacterial meningitis in 53 (34.4%) patients. Four variables were significantly associated with bacterial aetiology: cerebrospinal fluid (CSF) lactate concentration >=33mg/dl (odds ratio [OR] 50.84; 95% confidence interval [CI]: 21.63-119.47, P<.001), serum procalcitonin (PCT) >=0.8ng/ml (OR 46.34; 95%CI: 19.71-108.89; P<.001), CSF glucose <60% of blood value (OR 20.82; 95%CI: 8.86-48.96; P=.001), CSF polymorphonuclears greater than 50% (OR 20.19; 95%CI: 8.31-49.09; P=.002]. The area under the curve for the model serum PCT>=0.8ng/ml plus CSF lactate >=33mg/dl was 0.992 (95%CI: 0.979-1; P<.001), and achieved 99% sensitivity and 98% specificity for predicting bacterial meningitis. CONCLUSIONS: Serum PCT with CSF lactate, CSF glucose and CSF polymorphonuclears evaluated in an initial assessment in the ED for patients with AM, achieved an excellent diagnostic usefulness for predicting bacterial meningitis. PMID- 26994814 TI - First case of imported Zika virus infection in Spain. AB - We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barre syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored. PMID- 26994815 TI - Meningococcemia in vaccinated patient under treatment with eculizumab. PMID- 26994816 TI - Oral superficial mucocele in cancer patients. PMID- 26994818 TI - In vitro inhibition of Plasmodium falciparum early and late stage gametocyte viability by extracts from eight traditionally used South African plant species. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of plant species, used traditionally to treat malaria, have been extensively investigated for their activity against Plasmodium intraerythrocytic asexual parasites in search of new antimalarial drugs. However, less effort has been directed towards examining their efficacy in blocking transmission. Here, we report the results of the in vitro screening of extracts from eight selected plant species used traditionally to treat malaria in South Africa for activity against Plasmodium falciparum NF54 early and late stage gametocytes. The species used were Khaya anthotheca, Trichilia emetica, Turraea floribunda, Leonotis leonurus, Leonotis leonurus ex Hort, Olea europaea subsp. Africana, Catha edulis and Artemisia afra. AIM OF THE STUDY: To investigate the activities of extracts from plant species traditionally used for malaria treatment against P. falciparum gametocytes. MATERIAL AND METHODS: Air-dried and ground plant leaves were extracted using acetone. Primary two point in vitro phenotypic screens against both early and late stage gametocytes were done at 10 and 20ug/ml followed by full IC50 determination of the most active extracts. Inhibition of gametocyte viability in vitro was assessed using the parasite lactate dehydrogenase (pLDH) assay. RESULTS: Of the eight crude acetone extracts from plant species screened in vitro, four had good activity with over 50-70% inhibition of early and late stage gametocytes' viability at 10 and 20ug/ml, respectively. Artemisia afra (Asteraceae), Trichilia emetica (Meliaceae) and Turraea floribunda (Meliaceae) were additionally highly active against both gametocyte stages with IC50 values of less than 10ug/ml while Leonotis leonurus ex Hort (Lamiaceae) was moderately active (IC50<20ug/ml). The activity of these three highly active plant species was significantly more pronounced on late stage gametocytes compared to early stages. CONCLUSION: This study shows the potential transmission blocking activity of extracts from selected South African medicinal plants and substantiates their traditional use in malaria control that broadly encompasses prevention, treatment and transmission blocking. Further studies are needed to isolate and identify the active principles from the crude extracts of A. afra, T. emetica and T. floribunda, as well as to examine their efficacy towards blocking parasite transmission to mosquitoes. PMID- 26994817 TI - Medicinal plant Combretum leprosum mart ameliorates motor, biochemical and molecular alterations in a Parkinson's disease model induced by MPTP. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Combretum leprosum is a popular medicinal plant distributed in north and northeastern regions of Brazil. Many different parts of this plant are used in traditional medicine to treat several inflammatory diseases. Parkinson's disease (PD) is a disorder associated with inflammatory toxic factors and the treatments available provide merely a delay of the neurodegeneration. AIM OF THE STUDY: We investigated the potential neuroprotective properties of the C. leprosum ethanolic extract (C.l.EE) in a murine model of PD using the toxin 1-methyl-4 phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP). MATERIALS AND METHODS: The mice were split into four groups: V/S (vehicle/saline), E/S (extract/saline), V/M (vehicle/MPTP) and E/M (extract/ MPTP). Mice received MPTP (30mg/kg, i.p.) or vehicle (10ml/kg, i.p.) once a day for 5 consecutive days and vehicle (10ml/kg) or C.l.EE (100mg/kg) orally by intra-gastric gavage (i.g.) during a 14-d period, starting 3 days before the first MPTP injection. All groups were assessed for behavioural impairments (amphetamine-induced locomotor activity and muscle strength), dopamine content in striatum using high performance liquid chromatography (HPLC), tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene expressions using qPCR. RESULTS: Animals were injected with d-amphetamine (2mg/kg) and the activity was recorded. Amphetamine-induced hyperlocomotion was observed in all groups; however animals treated with MPTP showed exacerbated hyperlocomotion (approximately 3 fold increase compared to control groups). By contrast, mice treated with MPTP that received C.l.EE exhibited attenuation of the hyperlocomotion and did not differ from control groups. Muscle strength test pointed that C.l.EE strongly avoided muscular deficits caused by MPTP (approximately 2 fold increase compared to V/M group). Dopamine and its metabolites were measured in the striatum. The V/M group presented a dopamine reduction of 80%. On the other hand, the E/M group exhibited an increase in dopamine and its metabolites levels (approximately 3 fold increase compared to V/M group). Tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene expressions were significantly reduced in the V/M group (60%). Conversely, C.l.EE treatment was able to increase the mRNA levels of those genes in the E/M group (approximately 2 fold for TH and DAT). CONCLUSIONS: These data show, for the first time, that C. leprosum ethanolic extract prevented motor and molecular changes induced by MPTP, and partially reverted dopamine deficit. Thus, our results demonstrate that C.l.EE has potential for the treatment and prevention of PD. PMID- 26994819 TI - Chotosan improves Abeta1-42-induced cognitive impairment and neuroinflammatory and apoptotic responses through the inhibition of TLR-4/NF-kappaB signaling in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Recently, the focus on neuroinflammation is intensified as its complex pathophysiological role has emerged in multiple central nervous system(CNS) disorders. Chotosan (CTS), known as a traditional herbal formula, is often utilized to treat relevant nervous system diseases in China. It was demonstrated effectively to alleviate cognitive deficit associated with aging, diabetes, hypoperfusion and cerebral ischemia. However, the effects of CTS on Abeta1-42-induced cognitive dysfunction remain unclear. Here, we further investigated the effects of chotosan on memory performance, neuroinflammation and apoptotic responses. MATERIALS AND METHODS: The learning and memory ability is evaluated by Morris water maze (MWM) task and Y-maze test following intrahippocampal infusion of aggregated Abeta1-42. The expression level of toll-like receptor 4 (TLR-4), NF-kappaB p65, Bcl-2 and Bax was examined by Western blot. TLR-4 level is also assessed by immunohistochemistry (IHC). Enzyme linked immunosorbent assay (ELISA) was conducted to determine the generation of inflammatory mediators. The caspase-3 activity is analyzed by commercial kits. RESULTS: The repeated treatment with CTS (750mg/kg or 375mg/kg per day) for 3 weeks significantly restored Abeta1-42-induced memory impairment in mice. Meanwhile, this treatment also remarkably reduced TLR-4 and NF-kappaB p65 expression accompanying with the diminished release of proinflammatory cytokines including TNF-alpha and IL-1beta in hippocampus. The neuronal apoptosis is also inhibited as evidenced by increase in Bcl-2/Bax ratio and decrease in pro apoptotic protein caspase-3 activity compared to that of the model mice. CONCLUSIONS: Our results show for the first time that chotosan can ameliorate Abeta1-2-induced memory dysfunction via inhibiting neuroinflammation and apoptosis at least partially mediated by TLR-4/NF-kappaB signaling pathway. PMID- 26994820 TI - Sphingosine-1-phosphate induces COX-2 expression and PGE2 production in human granulosa cells through a S1P1/3-mediated YAP signaling. AB - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that can regulate various physiological and pathological processes. The expression of S1P has been detected in human follicular fluid. In addition, two S1P receptors, S1P1 and S1P3, are expressed at a high level in human granulosa cells. Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production plays a critical role in the regulation of ovulation. However, thus far, the effect of S1P on COX-2 expression and PGE2 production in human granulosa cells remains unknown. In the present study, our results demonstrated that treatment with S1P significantly induced COX 2, but not COX-1, expression and increased PGE2 production in human granulosa cells. The stimulatory effects of S1P on COX-2 expression and PGE2 production were attenuated by treatment with specific antagonist of S1P1 or S1P3 and siRNA mediated knockdown of S1P1 or S1P3. In addition, the COX-2 expression was induced by S1P1 or S1P3 agonist treatment. Interestingly, treatment with S1P activated YAP signaling via S1P1 and S1P3. Moreover, knockdown of YAP partially attenuated S1P-induced COX-2 expression and PGE2 production. These results provide evidence that S1P induces COX-2 expression and PGE2 production in human granulosa cells through a S1P1/3-mediated YAP signaling pathway. PMID- 26994821 TI - Targeting thrombin long-term after an acute coronary syndrome: Opportunities and challenges. AB - Patients after an acute coronary syndrome (ACS) are at increased risk of recurrent thrombotic events, justifying the search for additional antithrombotic treatments. The pathophysiology of ACS involves arterial thrombus formation, in turn occurring because of a combination of platelet activation and fibrin formation, with thrombin playing a key role in both. Antiplatelet therapy, targeting the thromboxane pathway and the ADP P2Y12 receptor has been widely accepted for secondary prevention after an ACS. Now, data from recent clinical trials in such patients also encourage the pursuit of inhibiting thrombin formation or thrombin-mediated platelet activation in addition to antiplatelet therapy. This "triple pathway inhibition", including inhibition of thrombin activity or thrombin receptor(s), is currently an option in pure ACS, but already a must in the setting of ACS accompanied by atrial fibrillation (AF), where anticoagulants have been shown to be much more effective than antiplatelet agents in preventing stroke. We here discuss the challenges of managing combined thrombin activity or receptor inhibition and antiplatelet therapy in all such patients. Translating this into practice still requires further studies and patient tailoring to fully exploit its potential. PMID- 26994822 TI - Localization of angiotensin receptor type 2 in fetal bovine ovaries. AB - In the ovary, angiotensin II (ANGII) acts through the type 2 receptor (AGTR2) to induce ovulation and may play a role in follicle atresia. In this study, we determined the expression of AGTR2 mRNA and protein during follicle formation in the bovine ovary. Female fetuses at different gestational ages (60, 75, 90, 120, 150 and 210 days) were used for immunolocalization of AGTR2. At day 60, AGTR2 was localized to the cytoplasm of oogonia; from days 75 to 150, during follicle formation and development to secondary stage, AGTR2 immunostaining was weak and irregular, but from day 210 staining became evident in granulosa cells of preantral follicles and in both granulosa and theca cells of small antral follicles. These data differ from those in pigs, in which AGTR2 protein is detected in preantral follicles throughout gestation. Abundance of AGTR2 mRNA in whole ovaries did not change with fetal age. In conclusion, AGTR2 protein is expressed in ovigerous cords in fetal bovine ovaries but not in preantal follicles until the formation of antral follicles. These data suggest important species-specific differences in the expression of AGTR2 in fetal ovaries from polyovulatory and monovulatory animals. PMID- 26994823 TI - The effect of a combined strength and proprioceptive training on muscle strength and postural balance in boys with intellectual disability: An exploratory study. AB - The aim of our study was to investigate the effect of a combined strength and proprioception training (CSPT) program on muscle strength and postural balance in children with intellectual disability (ID). The maximum voluntary contraction (MVC) and postural parameters (CoPVm, CoPLX, CoPLY) of 20 children with ID were recorded before and after 8 weeks of a CSPT program. The participants were divided into two groups: an experimental group who attended a CSPT program and a control group who continued with daily activities. In the trained group, the MVC increased significantly (p<0.001) after the training period and the postural parameters decreased significantly in Double-Leg Stance (DLS) and One-Leg Stance (OLS) during the firm surface condition as well as in the DLS during the foam surface condition; in both eyes open (EO) and eyes closed (EC) conditions. A CSPT program improves postural balance in children with ID could be due to the enhancement in muscle strength and proprioceptive input integration. PMID- 26994824 TI - Evaluation of the setup margins for cone beam computed tomography-guided cranial radiosurgery: A phantom study. AB - The aim of this study is to evaluate the setup margins from the clinical target volume (CTV) to planning target volume (PTV) for cranial stereotactic radiosurgery (SRS) treatments guided by cone beam computed tomography (CBCT). We designed an end-to-end (E2E) test using a skull phantom with an embedded 6mm tungsten ball (target). A noncoplanar plan was computed (E2E plan) to irradiate the target. The CBCT-guided positioning of the skull phantom on the linac was performed. Megavoltage portal images were acquired after 15 independent deliveries of the E2E plan. The displacement 2-dimensional (2D) vector between the centers of the square field and the ball target on each portal image was used to quantify the isocenter accuracy. Geometrical margins on each patient's direction (left-right or LR, anterior-posterior or AP, superior-inferior or SI) were calculated. Dosimetric validation of the margins was performed in 5 real SRS cases: 3-dimesional (3D) isocenter deviations were mimicked, and changes in CTV dose coverage and organs-at-risk (OARs) dosage were analyzed. The CTV-PTV margins of 1.1mm in LR direction, and 0.7mm in AP and SI directions were derived from the E2E tests. The dosimetric analysis revealed that a 1-mm uniform margin was sufficient to ensure the CTV dose coverage, without compromising the OAR dose tolerances. The effect of isocenter uncertainty has been estimated to be 1mm in our CBCT-guided SRS approach. PMID- 26994825 TI - Linac-based extracranial radiosurgery with Elekta volumetric modulated arc therapy and an anatomy-based treatment planning system: Feasibility and initial experience. AB - We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. For a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36min/Gy. The mean number of monitor units was 3162, i.e., 121.6MU/Gy. Pretreatment verification (3%-3mm) showed an optimal agreement with calculated values; mean gamma value was 0.27 and 98.2% of measured points resulted with gamma < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity. PMID- 26994826 TI - Simple shielding reduces dose to the contralateral breast during prone breast cancer radiotherapy. AB - Our goal was to design a prone breast shield for the contralateral breast and study its efficacy in decreasing scatter radiation to the contralateral breast in a prone breast phantom setup receiving radiation therapy designed for breast cancer. We constructed a prone breast phantom setup consisting of (1) A thermoplastic mask with a left-sided depression created by a water balloon for a breast shape; (2) 2 plastic bags to hold water in the thermoplastic mask depression; (3) 2000mL of water to fill the thermoplastic mask depression to create a water-based false breast; (4) 1-cm thick bolus placed in the contralateral breast holder; (5) 2 lead (Pb) sheets, each 0.1-cm thick for blocking scatter radiation in the contralateral bolus-based false breast; (6) a prone breast board to hold the thermoplastic mask, water, bolus, and lead; (7) 9cm solid water on top of the breast board to simulate body; (8) a diode was used to verify dose for each treatment field of the treated water-based breast; (9) metal-oxide-semiconductor-field effect transistor (MOSFET) dosimeters to measure dose to the contralateral bolus-based breast. The phantom prone breast setup was CT simulated and treatment was designed with 95% isodose line covering the treated breast. The maximum dose was 107.1%. Megavoltage (MV) port images ensured accurate setup. Measurements were done using diodes on the treated water-based breast and MOSFET dosimeters at the medial and lateral sides of the contralateral bolus-based breast without and with the Pb shield. Five treatments were done for each of the 3 data sets and recorded individually for statistical purposes. All treatments were completed with 6MV photons at 200cGy per treatment. The dose contributions from each of the 3 data sets including 15 treatments total without and with the prone lead shield to the medial and lateral portions of contralateral bolus-based breast were averaged individually. Unshielded dose means were 37.11 and 2.94cGy, and shielded dose means were 12.68 and 1.54cGy, respectively. When comparing medial and lateral portions of the contralateral bolus-based doses without and with Pb, the shield significantly reduced dose to both sides of the contralateral breast (medial p = 2.64 * 10(-14), lateral p = 4.91 * 10(-6)). The prone 0.2-cm Pb shield significantly reduced scatter dose to the contralateral breast on the order of 2 to 3 times. Reductions may be clinically relevant for women younger than 45 years by decreasing the risk of contralateral radiation-induced breast cancer in patients receiving radiation therapy for breast cancer. This shield is simple as it would be a part of the prone breast board during treatments, but future studies are warranted for safety and efficacy clinically. PMID- 26994827 TI - Accuracy evaluation of the optical surface monitoring system on EDGE linear accelerator in a phantom study. AB - Frameless stereotactic radiosurgery (SRS) requires dedicated systems to monitor the patient position during the treatment to avoid target underdosage due to involuntary shift. The optical surface monitoring system (OSMS) is here evaluated in a phantom-based study. The new EDGE linear accelerator from Varian (Varian, Palo Alto, CA) integrates, for cranial lesions, the common cone beam computed tomography (CBCT) and kV-MV portal images to the optical surface monitoring system (OSMS), a device able to detect real-time patient's face movements in all 6 couch axes (vertical, longitudinal, lateral, rotation along the vertical axis, pitch, and roll). We have evaluated the OSMS imaging capability in checking the phantoms' position and monitoring its motion. With this aim, a home-made cranial phantom was developed to evaluate the OSMS accuracy in 4 different experiments: (1) comparison with CBCT in isocenter location, (2) capability to recognize predefined shifts up to 2 degrees or 3cm, (3) evaluation at different couch angles, (4) ability to properly reconstruct the surface when the linac gantry visually block one of the cameras. The OSMS system showed, with a phantom, to be accurate for positioning in respect to the CBCT imaging system with differences of 0.6 +/- 0.3mm for linear vector displacement, with a maximum rotational inaccuracy of 0.3 degrees . OSMS presented an accuracy of 0.3mm for displacement up to 1cm and 1 degrees , and 0.5mm for larger displacements. Different couch angles (45 degrees and 90 degrees ) induced a mean vector uncertainty < 0.4mm. Coverage of 1 camera produced an uncertainty < 0.5mm. Translations and rotations of a phantom can be accurately detect with the optical surface detector system. PMID- 26994828 TI - Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes. AB - PURPOSE: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes. MATERIALS AND METHODS: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian's Eclipse treatment planning software. Patients were treated with a median radiation dose of 45Gy (range: 37.5 to 50Gy) to the primary volume and 45Gy (range: 45 to 64.8Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient's treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient's treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%). RESULTS: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45Gy) for primary and nodal volumes on all patients (n = 10). For all patients, >=99.3% of the primary tumor volume received >= 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, >= 99.8% of the volume received >= 95% the prescribed dose and the average minimum dose was 93%. In evaluating individual IGRT sessions, we found that 6 patients had an estimated minimal nodal CTV dose less than 90% (range: 78 to 99%) of that planned. With a median follow-up of 42.5 months, 2 patients experienced systemic disease progression at an average of 19.6 months. One patient was found to have a local or regional failure with an average follow-up of 42 months. CONCLUSION: Using only 3 dimensional IGRT corrections in gynecological radiation allows excellent coverage of the primary target volume and good average nodal CTV coverage. If IGRT corrections are based on alignment to the primary tumor volume, and is only able to be corrected in 3 degrees, this can create situations in which nodal volumes may be under dosed. Utilizing multiple IGRT sessions appears to average out dose discrepancies over the course of treatment. The implication of underdosing in a single IGRT session needs further evaluation in future studies. Based on the concern of minimum dose to a nodal target volume, these findings may signal caution when using IGRT and IMRT in gynecological radiation patients. Possible techniques to overcome this situation may include averaging shifts between tumor and nodal volume, use of a treatment couch with 6 degrees of freedom, deformable registration, or adaptive planning. PMID- 26994829 TI - Mapping the distribution of serotonin transporter in the human brainstem with high-resolution PET: Validation using postmortem autoradiography data. AB - The human brainstem is a complex structure with several small nuclei and neural pathways of interest in the pathophysiology of central nervous system (CNS) disorders. In common with other monoaminergic systems, serotoninergic neurons originate from a group of nuclei located in the brainstem. The present study was designed to validate a user-independent approach for a detailed in vivo quantification of serotonin transporter (5-HTT) availability in the human brainstem using a template-based approach that consisted of three steps. First, 3T-MR images and parametric binding potential (BPND) [(11)C]MADAM images of ten healthy subjects were used to generate a PET template of 5-HTT availability. In the second step, volumes of interest (VOIs) for different brainstem nuclei were obtained using a method in which VOIs are initially delineated on MRI images using anatomical landmarks and then are finally tailored on the distribution of 5 HTT binding using a thresholding approach applied to the 5-HTT template. In the final step, the VOIs were transformed and applied individually to BPND images of 16 healthy subjects (14M/2F, 20-64years). The in vivo distribution of BPND values obtained with the template-based method were in good agreement with an individual based approach taken as gold standard. Results were also in agreement with 5-HTT quantification using in vitro binding data obtained with autoradiography (ARG) studies using [(3)H]MADAM. The proposed template-based method can be applied to PET data acquired in several CNS disorders in which serotonin neurons in the brainstem might be affected. PMID- 26994830 TI - DNA double-strand breaks and micronuclei in human blood lymphocytes after repeated whole body exposures to 7T Magnetic Resonance Imaging. AB - PURPOSE: To examine the extent of genetic damage, assessed from deoxyribonucleic acid (DNA) double-strand breaks (DSBs) and micronuclei (MN) in peripheral blood mononuclear cells obtained from individuals repeatedly exposed to 7T Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: The study protocol was approved by the local ethics committee. Informed consent was obtained from 22 healthy, non smoking, non-alcoholic male individuals, who had never undergone radio-/chemo therapy, scintigraphy, and had not undergone X-ray examination one year prior blood withdrawal. Eleven participants were repeatedly exposed to 7T and 3T MRI while working with/around scanners or frequently participating as 7T and lower field MRI research subjects (mean age 34+/-7years). The other half was never exposed to 7T or lower field MRI and served as controls (mean age 33+/-9years). The damage in lymphocytes was assessed using anti-gammaH2AX immunofluorescence staining of DNA DSBs and by quantification of MN. Isolated cells were further exposed in vitro to 7T MRI either alone or in the presence of the DNA damaging drug etoposide, to determine if there is any additional combined effect. The kinetics of DNA damage repair were examined. RESULTS: The mean base-level of gammaH2AX foci/cell and incidence of MN between repeatedly exposed and control group were not significantly different (P=0.618 and P=0.535, respectively). The additional in vitro exposure of cells to 7T MRI had no significant impact on MN frequencies and gammaH2AX foci at 1, 20 and 72h after exposure. CONCLUSION: Frequently repeated 7T MRI exposure did not result in a detectable increase in genotoxicity indices and alterations of DNA repair kinetics. PMID- 26994831 TI - Rapid and specific gray matter changes in M1 induced by balance training. AB - Training-induced changes in cortical structure can be observed non-invasively with magnetic resonance imaging (MRI). While macroscopic changes were found mainly after weeks to several months of training in humans, imaging of motor cortical networks in animals revealed rapid microstructural alterations after a few hours of training. We used MRI to test the hypothesis of immediate and specific training-induced alterations in motor cortical gray matter in humans. We found localized increases in motor cortical thickness after 1h of practice in a complex balancing task. These changes were specific to motor cortical effector representations primarily responsible for balance control in our task (lower limb and trunk) and these effects could be confirmed in a replication study. Cortical thickness changes (i) linearly increased across the training session, (ii) occurred independent of alterations in resting cerebral blood flow and (iii) were not triggered by repetitive use of the lower limbs. Our findings show that motor learning triggers rapid and specific gray matter changes in M1. PMID- 26994832 TI - Shedding light on emotional perception: Interaction of brightness and semantic content in extrastriate visual cortex. AB - The rapid extraction of affective cues from the visual environment is crucial for flexible behavior. Previous studies have reported emotion-dependent amplitude modulations of two event-related potential (ERP) components - the N1 and EPN - reflecting sensory gain control mechanisms in extrastriate visual areas. However, it is unclear whether both components are selective electrophysiological markers of attentional orienting toward emotional material or are also influenced by physical features of the visual stimuli. To address this question, electrical brain activity was recorded from seventeen male participants while viewing original and bright versions of neutral and erotic pictures. Bright neutral scenes were rated as more pleasant compared to their original counterpart, whereas erotic scenes were judged more positively when presented in their original version. Classical and mass univariate ERP analysis showed larger N1 amplitude for original relative to bright erotic pictures, with no differences for original and bright neutral scenes. Conversely, the EPN was only modulated by picture content and not by brightness, substantiating the idea that this component is a unique electrophysiological marker of attention allocation toward emotional material. Complementary topographic analysis revealed the early selective expression of a centro-parietal positivity following the presentation of original erotic scenes only, reflecting the recruitment of neural networks associated with sustained attention and facilitated memory encoding for motivationally relevant material. Overall, these results indicate that neural networks subtending the extraction of emotional information are differentially recruited depending on low-level perceptual features, which ultimately influence affective evaluations. PMID- 26994833 TI - Cooling and freezing of sperm from captive, free-living and endangered squirrel monkey species. AB - Germoplasm banking is an important tool for the preservation of genetic material from Neotropical primates in captivity, and from free living species, especially the endangered ones like Saimiri vanzolinii (Black-headed squirrel monkey), a primate with a low incidence area (870 km(2) of floodplains) in the southern part of the Mamiraua Sustainable Development Reserve, Brazil. Therefore, in the present study we aimed to develop a sperm cryopreservation protocol comparing sperm cooling in presence (T1) and absence (T2) of egg yolk, and to test freezing protocols to preserve semen from captive (Saimiri collinsi), and free-living (Saimiri vanzolinii, Saimiri cassiquiarensis and Saimiri macrodon) New World primates. Cooling preserved sperm of S. collinsi in all evaluated microscopic parameters, except for sperm motility. No differences were observed among the treatments, indicating that semen of this species can be cooled without egg yolk. Freezing did not affect sperm quality of S. collinsi, except plasma membrane integrity that was negatively affected. Generally, a good maintenance rate was observed between cooling and thawing of semen for the four species, showing the positive translational application of protocols from S. collinsi to the free living species. Developed freezing protocol proved to be useful for sperm cryopreservation of S. collinsi and in field conditions. PMID- 26994834 TI - Predictors of Recanalization of the Great Saphenous Vein in Randomized Controlled Trials 1 Year After Endovenous Thermal Ablation. AB - OBJECTIVE/BACKGROUND: The objective was to identify predictors to develop and validate a prognostic model of recanalization of the great saphenous vein (GSV) in patients treated with endovenous thermal ablation (EVTA). METHODS: The search strategy of Siribumrungwong was updated between August 2011 and August 2014 using MEDLINE, Embase, and the Cochrane register to identify randomized controlled trials (RCTs), in which patients presenting with GSV reflux were treated with radiofrequency or endovenous laser ablation. Leg level data (n = 1226) of 15/23 selected RCTs were pooled. The primary outcome was recanalization of the GSV; the secondary outcome was change in health related quality of life (HRQoL) measured by the Chronic Venous Insufficiency quality of life Questionnaire or Aberdeen Varicose Vein Questionnaire 1 year post-procedure. Candidate predictors were age, sex, body mass index, clinical class, GSV diameter, saphenofemoral junction reflux, type of device, energy, and length of treated vein. RESULTS: At 1 year, 130 GSVs were recanalized (11%). Clinical class (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.4-3.3) and diameter (OR 1.8, 95% CI 1.2-2.7) of the GSV were the strongest predictors of recanalization. Other predictors included in the final model were sex, type of device, and length of treated vein. The performance of the recanalization model was moderate, with an area under the curve above 0.717. GSV diameter, type of device, and amount of energy delivered were the only predictors of the change of HRQoL. None of the candidate predictors were included in the final HRQoL model (R(2) = .027). CONCLUSION: There are several important prognostic factors for GSV recanalization and change of HRQoL after EVTA. However, the performance of each model was unsatisfactory to allow use in clinical practice yet. PMID- 26994835 TI - Distribution and depth profiles of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and polychlorinated biphenyls in sediment collected from offshore waters of Central Vietnam. AB - Concentrations of PCBs and OCPs were measured in 35 surface sediment samples collected from offshore waters of Central Vietnam. The mean concentrations of PCBs, HCHs, and DDTs in surface sediments were 86.5, 37.0, and 44.5pgg(-1), respectively. Additionally, nine PCDDs, eleven PCDFs, and twelve dl-PCBs were also examined in 19 sediment core samples collected from five locations. Concentration of PCDDs, PCDFs, and dl-PCBs ranged from 200 to 460, 0.39 to 2.9, and 1.6 to 22pgg(-1), respectively. OCDD was detected at the highest concentration, ranged from 100 to 300pgg(-1). Generally, the concentrations of PCDD/Fs at shallower depths were higher, meanwhile the depth profiles of dl-PCBs in sediment cores were different than the depth profiles of PCDD/Fs. The results suggest that the pollution of PCBs might be from many different sources leading to the variation between depths. PMID- 26994836 TI - Use of the Atlantic nut clam (Nucula proxima) and catworm (Nephtys incisa) in a sentinel species approach for monitoring the health of Bay of Fundy estuaries. AB - Designing an effective environmental monitoring system for population responses requires knowledge of the biology of appropriate sentinel species and baseline information on the area's physical and chemical characteristics. This study collected information in Saint John Harbor, NB, Canada, for two abundant marine benthic invertebrates, the Atlantic nut clam (Nucula proxima) and the catworm (Nephtys incisa) to characterize their seasonal and spatial variability, determine the ideal sampling time and methods, and develop baseline data for future studies. We also evaluated whether contamination is impacting invertebrates by comparing sediment metal concentrations to responses of benthic infauna. Metals were generally below sediment quality guidelines except for nickel and arsenic. Clam densities were variable between sites but not seasons, whereas catworm densities were not significantly different between sites or seasons. Overall, these species show potential for environmental monitoring, although investigation at more contaminated sites is warranted to assess their sensitivity. PMID- 26994837 TI - Isolation, identification, and crude oil degradation characteristics of a high temperature, hydrocarbon-degrading strain. AB - In this work, a hydrocarbon-degrading bacterium Y-1 isolated from petroleum contaminated soil in the Dagang Oilfield was investigated for its potential effect in biodegradation of crude oil. According to the analysis of 16S rRNA sequences, strain Y-1 was identified as Bacillus licheniformis. The growth parameters such as pH, temperature, and salinity were optimised and 60.2% degradation of crude oil removal was observed in 5days. The strain Y-1 showed strong tolerance to high salinity, alkalinity, and temperature. Emplastic produced by strain Y-1 at high temperatures could be applied as biosurfactant. Gas chromatography analysis demonstrated that the strain Y-1 efficiently degraded different alkanes from crude oil, and the emplastic produced by strain Y-1 promoted the degradation rates of long-chain alkanes when the temperature increased to 55 degrees C. Therefore, strain Y-1 would play an important role in the area of crude oil contaminant bioremediation even in some extreme conditions. PMID- 26994838 TI - A Case Report and Literature Review of Spontaneous Perforation of Pyometra. AB - BACKGROUND: Pyometra is defined as an accumulation of purulent material in the uterine cavity. Spontaneous perforation is a very rare complication of pyometra. The clinical findings of perforated pyometra are similar to perforation of the gastrointestinal tract and other causes of acute abdomen. CASE REPORT: We report a rare and difficult case of peritonitis in an elderly female that was caused by a spontaneous perforation of pyometra. A 90-year-old postmenopausal woman was referred to our hospital with complaints of vomiting, fever, and abdominal pain. Computed tomography revealed a large amount of ascites, cystic mass in the uterus, and intraperitoneal and intrauterine air. Transvaginal ultrasound demonstrated a thin area around the fundus. An emergency laparotomy was performed for the suspected gastrointestinal perforation or perforation of pyometra. At laparotomy, copious purulent fluid was present in the peritoneal cavity; however, no perforation of the gastrointestinal tract was observed. We identified a perforation site over the uterine fundus and purulent material exuding from the cavity. Subsequently, hysterectomy and bilateral salpingo-oophorectomy were performed. The patient was discharged on postoperative day 13 with no complications. Histopathologic studies revealed endometritis and myometritis with no evidence of malignancy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: With diffuse peritonitis, ruptured pyometra should be considered, even in elderly female patients. This case illustrates the importance of clinical knowledge of acute gynecologic diseases. Here we also review the perforation of pyometra with no evidence of malignancy. PMID- 26994839 TI - Distinct mechanisms of the newborn innate immunity. AB - The ontogeny of immunity during early life is of high importance as it shapes the immune system for the entire course of life. The microbiome and the environment contribute to the development of immunity in newborns. As immune responses in newborns are predominantly less experienced they are increasingly susceptible to infections. Though the immune cells in newborns are in 'naive' state, they have been shown to mount adult-like responses in several circumstances. The innate immunity plays a vital role in providing protection during the neonatal period. Various stimulants have been shown to enhance the potential and functioning of the innate immune cells in newborns. They are biased against the production of pro-inflammatory cytokines and this makes them susceptible to wide variety of intracellular pathogens. The adaptive immunity requires prior antigenic experience which is very limited in newborns. This review discusses in detail the characteristics of innate immunity in newborns and the underlying developmental and functional mechanisms involved in the immune response. A better understanding of the immunological milieu in newborns could help the medical fraternity to find novel methods for prevention and treatment of infection in newborns. PMID- 26994841 TI - Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents. AB - A series of novel isosteviol derivatives bearing amino alcohol and thiourea fragments have been stereo-selectively synthesized and screened for their in vitro cytotoxic activities against three human cancer cell lines (HCT-116, HGC-27 and JEKO-1). The results demonstrated that these compounds exhibited prominent cytotoxicities. Especially, the compound Iw displayed the most potent anticancer activities against HCT-116 cell with IC50 value of 1.450 MUM. On the basis of this bioassay results, these derivatives were further investigated by the hologram quantitative structure-activity relationship (HQSAR) technique. The optimal HQSAR model with q(2) = 0.663, r(2) = 0.895, SEE = 0.179 was generated using A/B/H/Ch as fragment distinction parameters and 4-7 as fragment size. This model was employed to predict the cytotoxic activities of test set compounds, and the predicted values were in good agreement with the experimental results. The contribution maps derived from the optimal model explained the individual atomic contribution to the total activity of single molecule. PMID- 26994840 TI - Comparison of susceptibility of Chilo suppressalis and Bombyx mori to five Bacillus thuringiensis proteins. AB - Transformation of rice with genes encoding insecticidal Cry proteins from Bacillus thuringiensis (Bt) should confer high resistance to target lepidopteran pests, such as Chilo suppressalis, and low toxicity to non-target organisms, such as silkworm Bombyx mori. Five purified Cry proteins that have been used for plant transformation were tested using dietary exposure assays. The susceptibility of C. suppressalis larvae to the five insecticidal proteins in the decreasing order was: Cry1Ca>Cry1Ab>Cry1Ac>Cry2Aa>Cry1Fa. However, the toxicities of the Cry proteins to B. mori were in the order: Cry1Fa>Cry1Ca>Cry2Aa>Cry1Ab>Cry1Ac. The Cry1Ca, Cry1Ab and Cry1Ac proteins exhibited relatively high toxicity to C. suppressalis larvae, with EC50 values of 16.4, 45.8 and 89.6ng/g, respectively. The toxicities of the three Cry proteins to B. mori larvae were 8, 14, and 22times lower, with EC50 values of 138.3, 628.4 and 1939.2ng/g, respectively. The Cry1Fa and Cry2Aa proteins showed high toxicity to B. mori larvae, with EC50 values of 135.7 and 373.9ng/g, respectively, but low toxicity to C. suppressalis larvae, with EC50 values of 6092.1 and 1208.5ng/g, respectively. We thus conclude that Cry1Ab, Cry1Ac and Cry1Ca are appropriate for transforming rice to control lepidopteran rice pests. In contrast, Cry1Fa and Cry2Aa are not appropriate due to their high toxicity to silkworm larvae and low activity against the target pest. PMID- 26994842 TI - New 3'-O-aromatic acyl-5-fluoro-2'-deoxyuridine derivatives as potential anticancer agents. AB - New aromatic and aliphatic 3'-O-acyl-5-fluoro-2'-deoxyuridine derivatives were synthesized and evaluated as candidates for prodrugs against various cancer cell lines. As the most promising candidate for antimalignant therapeutics was found a dual-acting acyl derivative 7h, which apparently released not only the known anticancer nucleoside, 5-fluoro-2'-deoxyuridine (FdU), but also an additional active metabolite, acetylsalicylic acid, reinforcing thus therapeutic effect of FdU. Promising therapeutic indices showed also some aromatic dicarboxylic acids derivatives decorated with FdU esters (11 and 12). PMID- 26994843 TI - Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket. AB - On the basis of structure-based bioisosteric replacement and molecular hybridization strategy, a series of novel dual structural-conformation inhibitors targeting the "entrance channel" of HIV-1 NNRTIs binding pocket (NNIBP) were designed and synthesized. All of the new compounds were evaluated for their anti HIV activities in MT-4 cells using the MTT method. Five compounds exhibited moderate to excellent potencies inhibiting wild-type (wt) HIV-1 replication with EC50 values ranging from 31.36 MUM to 0.11 MUM. Among them, compound 15b was identified as the most potent inhibitor with EC50 values of 0.11 MUM and 2.18 MUM against wt and K103N/Y181C double mutant HIV-1 strain (RES056), respectively. In addition, preliminary structure-activity relationships (SARs) and molecular simulation studies were discussed, which may provide valuable insights for further optimization. PMID- 26994844 TI - Applying the designed multiple ligands approach to inhibit dihydrofolate reductase and thioredoxin reductase for anti-proliferative activity. AB - The development of multi-targeting drugs is currently being explored as an attractive alternative to combination therapy, especially for the treatment of complex diseases such as cancer. Dihydrofolate reductase (DHFR) and thioredoxin reductase (TrxR) are enzymes belonging to two unrelated cellular pathways that are known to contribute towards cancer cell growth and survival. In order to evaluate whether simultaneous inhibition of DHFR and TrxR by dihydrotriazines (DHFR-targeting) and chalcones (TrxR-targeting) may be beneficial, breast MCF-7 and colorectal HCT116 carcinoma cells were treated with combinations of selected dihydrotriazines and chalcones at a 1:1 M ratio. Two combinations demonstrated synergy at low-to-moderate concentrations. Based on this result, four merged dihydrotriazine-chalcone compounds were designed and synthesized. Two compounds, 11a [DHFR IC50 = 56.4 MUM, TrxR IC50 (60 min) = 12.6 MUM] and 11b [DHFR IC50 = 2.4 MUM, TrxR IC50 (60 min) = 10.1 MUM], demonstrated in vitro inhibition of DHFR and TrxR. The compounds showed growth inhibitory activity against MCF-7 and HCT116 cells, but lacked cytotoxicity. Molecular docking experiments showed 11b to possess rational binding modes to both the enzymes. In conclusion, this study has not only identified the dihydrotriazine and chalcone scaffolds as good starting points for the development of dual inhibitors of DHFR and TrxR, but also demonstrated the synthetic feasibility of producing a chemical entity that could result in simultaneous inhibition of DHFR and TrxR. Future efforts to improve the antiproliferative profiles of such compounds will look at alternative ways of integrating the two pharmacophoric scaffolds. PMID- 26994845 TI - Identification of leads for antiproliferative activity on MDA-MB-435 human breast cancer cells through pharmacophore and CYP1A1-mediated metabolism. AB - CYP1A1 is a potential target for anticancer drug development due to its overexpression in certain cancer cells and role in cancer progression. To identify new leads for CYP1A1 mediated anticancer action, we attempted ligand based pharmacophore mapping, virtual screening of databases, molecular docking, MetaSite based filtering, and molecular dynamics simulations. Initial computational and in vitro screening identified 11 compounds from which we identified two lead compounds, ZINC33468944 and ZINC32101539, showed potential antitumor activity on MDA-MB-435 cell lines (GI50 < 0.1 MUM) and CYP1A1 inhibition of 0.13 and 0.3 MUM, respectively. Furthermore, the lead compounds were evaluated for CYP1A1 mediated metabolism, showing N-hydroxylated metabolites, which have potential of DNA adduct formation and cause cancerous cell death. Analysis of molecular dynamics simulations provided important guidelines for the further modification of the lead compounds. Hence, we claim the lead molecules for further development in anticancer drug discovery. PMID- 26994846 TI - Synthesis and biological activities of indolizine derivatives as alpha-7 nAChR agonists. AB - Human alpha7 nicotinic acetylcholine receptor (nAChR) is a promising therapeutic target for the treatment of schizophrenia accompanied with cognitive impairment. Herein, we report the synthesis and agonistic activities of a series of indolizine derivatives targeting to alpha7 nAChR. The results show that all synthesized compounds have affinity to alpha7 nAChR and some give strong agonistic activity, particularly most active agonists show higher potency than control EVP-6124. The docking and structure-activity relationship studies provide insights to develop more potent novel alpha7 nAChR agonists. PMID- 26994847 TI - Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S) sulfonylamidine camptothecin derivatives. AB - In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure-activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and pi-pi stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity. PMID- 26994848 TI - Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin. AB - Systemic mastocytosis is a myeloproliferative neoplasm with varying presentation that is caused by infiltration of neoplastic mast cells into extracutaneous tissues. Cytoreductive therapy is used to control organ dysfunction in aggressive systemic mastocytosis and is sometimes needed for control of severe refractory symptoms in patients with indolent disease. However, current standard cytoreductive agents are limited by their suboptimal degree and duration of response and associated significant toxicities, highlighting the need for novel treatments for systemic mastocytosis. Recent studies have identified CD30 as a therapeutic target in systemic mastocytosis, as CD30 is expressed on a majority of neoplastic mast cells. In this case series, the clinical outcomes of 4 patients with aggressive or indolent systemic mastocytosis treated with the anti CD30 antibody-drug conjugate brentuximab vedotin are reported. Two patients showed evidence of a response to treatment with a reduction in disease burden, 1 of which has demonstrated a durable response with ongoing benefit for more than 3 years. Treatment with brentuximab vedotin was well-tolerated with side effects that were effectively managed by dose modifications. The results presented suggest that brentuximab vedotin is active in systemic mastocytosis and can induce durable responses with a manageable toxicity profile. PMID- 26994850 TI - Homoharringtonine, aclarubicin and cytarabine (HAA) regimen as the first course of induction therapy is highly effective for acute myeloid leukemia with t (8;21). AB - Homoharringtonine combined aclarubicin and cytarabine (HAA) has been demonstrated to achieve a high remission rate and provide a survival advantage in acute myeloid leukemia (AML). To investigate whether HAA is an ideal induction regimen for t(8;21)AML, we retrospectively analyzed the data of 140 patients from the last 8 years in our center. When achieving complete remission (CR), the post remission treatment was administered as a minimal residual disease-directed risk stratification treatment protocol. The RUNX1/RUNX1T1 transcript level was assessed by RT-qPCR. The last follow-up was conducted in October 2015. In total, thirty patients received an HAA regimen as the induction treatment. The CR rate after one cycle of the HAA regimen was 93.3% (28/30). One patient achieved partial remission, and one had no response. No patients died during induction treatment. The median fold decrease of the RUNX1/RUNX1T1 transcript level was 200 (1-358000), and 16.7% (5/30) patients achieved >3 log decrease after one cycle of the HAA regimen. The estimated 4-year disease-free survival and overall survival were 89.9% and 90.8%, respectively. We concluded that the HAA regimen is highly effective as the first course of induction therapy for t(8;21) AML, and this needs to be confirmed in a large population in the future. PMID- 26994849 TI - The prognostic significance of CD45 expression by clonal bone marrow plasma cells in patients with newly diagnosed multiple myeloma. AB - Evaluation of clonal plasma cells (PCs) in the bone marrow (BM) of multiple myeloma (MM) patients reveals two distinct clonal PC populations based on the presence or absence of CD45 expression. We explored the prognostic significance of CD45 expression by clonal PCs in the BM of MM patients in the era of novel agent therapy. All 156 MM patients seen at the Mayo Clinic, Rochester from 2009 to 2011 who had their BM evaluated by multiparametric flow cytometry were included. Patients whose BM had >=20% of the clonal PCs expressing CD45 were classified as CD45 positive (+) and the rest as CD45 negative (-). Of these patients, the median overall survival (OS) for patients in the CD45 (+) group (n=43, 28%) was 38 months versus not reached for the CD45 (-) group (n=113, 72%) (P=0.009). In a multivariable analysis, CD45 (+) status was an independent predictor of inferior OS among newly diagnosed patients with MM. CD45 expression may be a surrogate for a more aggressive phenotype of MM and warrants further investigation. PMID- 26994851 TI - Neighborhood Stress, Depressive Symptoms, and Asthma Morbidity in Youth. AB - OBJECTIVE: Living in a dangerous and disadvantaged neighborhood is consistently linked with poor health outcomes; however, few studies have investigated psychosocial mechanisms of this relationship. We hypothesized that a specific facet of depression-anhedonia-would partially explain the relationship between stressful neighborhoods and poor health in youth with asthma. METHOD: 156 youths provided reports on their depressive symptoms, daily asthma symptoms, and peak expiratory flow rate (PEFR). Caregivers provided reports on neighborhood characteristics. RESULTS: Youth residing in more at-risk neighborhoods experienced more symptoms of depression, greater asthma symptoms (both during the day and night), and marginally lower PEFR. Indirect effect analyses revealed that the relationship between neighborhood stress and youth asthma symptoms was partially explained by a key symptom of depression, anhedonia. CONCLUSIONS: These findings suggest that the neighborhood-health link is partially explained by symptoms of depression tapping into difficulties experiencing pleasure and motivation. PMID- 26994852 TI - Variations in Daily Sleep Quality and Type 1 Diabetes Management in Late Adolescents. AB - OBJECTIVE : To determine how between- and within-person variability in perceived sleep quality were associated with adolescent diabetes management. METHODS: A total of 236 older adolescents with type 1 diabetes reported daily for 2 weeks on sleep quality, self-regulatory failures, frequency of blood glucose (BG) checks, and BG values. Average, inconsistent, and daily deviations in sleep quality were examined. RESULTS : Hierarchical linear models indicated that poorer average and worse daily perceived sleep quality (compared with one's average) was each associated with more self-regulatory failures. Sleep quality was not associated with frequency of BG checking. Poorer average sleep quality was related to greater risk of high BG. Furthermore, inconsistent and daily deviations in sleep quality interacted to predict higher BG, with more consistent sleepers benefitting more from a night of high-quality sleep. CONCLUSIONS : Good, consistent sleep quality during late adolescence may benefit diabetes management by reducing self-regulatory failures and risk of high BG. PMID- 26994853 TI - Maternal Depressive Symptoms and Household Income in Relation to Sleep in Early Childhood. AB - OBJECTIVE : Sleep health is critical for children to adapt to evolving cognitive socioemotional contexts. Given that sleep timing in early childhood is instituted under caregiver control, the family context likely has an influential role on children's sleep. This study investigated links between maternal depressive symptoms and variability in children's sleep, and whether household income moderated this relation. METHOD : 90 children (Mage = 53 +/- 9 months) wore actigraphs to objectively measure sleep for 4-16 days. Mothers reported income and depressive symptomatology. RESULTS : Higher maternal depressive symptoms were related to greater variability in 24-hr sleep duration. Income moderated this relation. Lower income, but not maternal depressive symptoms, was linked to greater variability in sleep onset time. CONCLUSIONS : Findings demonstrate important relations between maternal depressive symptoms, income, and children's sleep. Understanding distal and proximal family characteristics that may be related to children's developing sleep schedules could help identify populations and strategies for promoting optimal sleep health. PMID- 26994854 TI - Dietary Intake and Eating-Related Cognitions Related to Sleep Among Adolescents Who Are Overweight or Obese. AB - OBJECTIVE : To examine associations of sleep duration and regularity with dietary intake and eating-related cognitions among adolescents who are overweight/obese. METHODS : Participants were 315 adolescents being evaluated through Healthy Kids, Healthy Weight. Outcomes were reported sleep duration and regularity (bedtime shift, wake-time shift, sleep duration shift). Major predictors were dietary intake (e.g., consumption of calories and sugar-sweetened beverages) and eating related cognitions (food preoccupation, eating self-efficacy). RESULTS : Findings were that staying up (i.e., bedtime shift) and sleeping in later (i.e., wake-time shift) on weekends compared with weekdays significantly relates to drinking more sugar-sweetened beverages, the latter for males. Sleeping in on weekends was related to greater food preoccupation. CONCLUSIONS : Sleep regularity was the most important variable in its relationships with dietary intake. Evaluating sleep patterns and improving them with behavioral interventions should be considered as an additional weight loss strategy to promote dietary adherence. PMID- 26994855 TI - Daily Sleep Patterns, Sleep Quality, and Sleep Hygiene Among Parent-Child Dyads of Young Children Newly Diagnosed With Juvenile Idiopathic Arthritis and Typically Developing Children. AB - OBJECTIVES: Describe daily sleep patterns, sleep quality, and sleep hygiene in 2 5-year-old children newly diagnosed with juvenile idiopathic arthritis (JIA) and their parents in comparison with typically developing (TD) children and parents. METHODS: Participants (13 JIA, 16 TD parent-child dyads) wore actigraphs for 10 days. Parents completed sleep diaries and sleep hygiene survey. RESULTS: Children with JIA had significantly less total sleep time, lower sleep efficiency (SE), and longer naps than TD children. Parents of children with JIA had significantly earlier bedtimes, more wake after sleep onset (WASO) and lower SE than TD parents. Parent-child SE and WASO were interrelated in JIA dyads. Sleep hygiene practices were inconsistent in both groups of children. CONCLUSIONS: Inadequate amounts of sleep and poor sleep quality were common in parent-child dyads. Early interventions to improve sleep duration and promote sleep hygiene practices may alleviate future sleep problems and improve parent and child well-being. PMID- 26994856 TI - How the Frailty Index May Support the Allocation of Health Care Resources: An Example From the INCUR Study. AB - BACKGROUND: The Frailty Index (FI), proposed by Rockwood and Mitniski, measures the deficits accumulation occurring with aging, and can be generated from the results of a comprehensive clinical assessment. Its construct (based on pure arithmetical assumptions) may represent a unique feature for supporting unbiased comparisons among clinical facilities/services. OBJECTIVE: To propose an example depicting how the FI may support health economic evaluations and provide insights for public health. DESIGN: Observational study. SETTING: Nine nursing homes participating in the "Incidence of pNeumonia and related ConseqUences in nursing home Residents" (INCUR) study. SUBJECTS: A sample of 345 older persons living in nursing homes. METHODS: A 30-item FI was generated from clinical data retrieved from medical charts. Health care expenditures that occurred over 12 months of follow-up for each participant were obtained from the Caisse Primaire d'Assurance Maladie. Descriptive analyses describing the relationships between the FI of residents with the annual health care expenditures according to nursing home are presented. RESULTS: Mean age of the study sample was 86.0 (SD 7.9) years. The median annual cost per patient was 27,717.75 (interquartile range, IQR 25,917.60 32,118.02) Euros. The median FI was 0.33 (IQR 0.27-0.43). Results are graphically presented to highlight clinical and economic differences across nursing homes, so as to identify potential discrepancies between clinical burden and consumed resources. CONCLUSIONS: In this article, an example on how the FI may support health economic analyses and promote an improved allocation of healthcare resources is presented. PMID- 26994857 TI - Polyethylene glycol fusion repair prevents reinnervation accuracy in rat peripheral nerve. AB - Functional recovery following a peripheral nerve injury is made easier when regenerating axons correctly reinnervate their original targets. Polyethylene glycol (PEG) has recently been used in attempts to fuse severed peripheral axons during suture-based repair, but an analysis of target selectivity following such repair has not been undertaken. The rat femoral nerve (in which muscle and cutaneous pathways comingle proximally but segregate distally into separate terminal nerve branches) is a convenient in vivo model for assessing motor neuron regeneration accuracy. The present study uses retrograde labeling of motor neurons to compare reinnervation accuracy after suture-based nerve repair with and without PEG fusion. The results show that adding PEG to the suture repair site blocked the preference of motor neurons to reinnervate correctly the distal terminal nerve branch to muscle that was seen with suture repair. Retrograde transport and diffusion studies also determined that PEG fusion allowed passage of probes across the repair site, as has previously been seen, but did not result in motor neuron labeling in the spinal cord. The results suggest that PEG fusion disrupts the beneficial trophic influence of muscle on motor neuron reinnervation accuracy normally seen after suture repair and that such fusion-based approaches may be best suited to nerve injuries in which accurate target reinnervation at the terminal nerve branch level is not a priority. (c) 2016 Wiley Periodicals, Inc. PMID- 26994858 TI - Efficient Discrimination of Single Nucleotide Polymorphisms (SNPs) Using Oligonucleotides Modified with C5-Pyrene-Functionalized DNA and Flanking Locked Nucleic Acid (LNA) Monomers. AB - Oligodeoxyribonucleotides modified with 5-[3-(1-pyrenecarboxamido)propynyl]-2' deoxyuridine monomer X and proximal LNA monomers display higher affinity for complementary DNA, more pronounced increases in fluorescence emission upon DNA binding, and improved discrimination of SNPs at non-stringent conditions, relative to the corresponding LNA-free probes across a range of sequence contexts. The results reported herein suggest that the introduction of LNA monomers influences the position of nearby fluorophores via indirect conformational restriction, a characteristic that can be utilized to develop optimized fluorophore-labeled probes for SNP-discrimination studies. PMID- 26994859 TI - Endovascular hyperacute stroke therapies - what do recent trials mean for children? PMID- 26994860 TI - Degeneration patterns of the worker spermatheca during morphogenesis in ants (Hymenoptera: Formicidae). AB - Reproductive division of labor is one of the crucial features in social insects, however, the developmental mechanisms leading to modifications in the reproductive apparatus of workers are still not very clear. Ants show a remarkable diversity in the morphological specialization of the worker's reproductive apparatus, that allows to distinguish four types, type 1: workers that have ovaries and a functional spermatheca, and that reproduce like queens, type 2: workers have ovaries and a vestigial spermatheca, type 3: workers have ovaries but no spermatheca, and type 4: workers lost both ovaries and spermatheca. We investigated morphogenesis of the worker spermatheca in 28 ant species by histological examination. In workers of type 1, the morphogenesis of the spermatheca is very similar to that in ant queens. In type 2, the spermathecal disc also differentiates, however, the development is interrupted and remains vestigial. In types 3 and 4, the absence of the spermatheca in the adult phase is caused by a degeneration after initial formation of the spermathecal disc or by a complete lack of the spermathecal discs. The timing of these interruption and degeneration events varies among species. The species exhibiting an earlier interrupting point of spermatheca formation in workers have a larger queen-worker dimorphism, that seems to be independent from ant phylogeny. PMID- 26994861 TI - Sex beyond species: the first genetically analyzed case of intergeneric fertile hybridization in pinnipeds. AB - A species, according to the biological concept, is a natural group of potentially interbreeding individuals isolated by diverse mechanisms. Hybridization is considered the production of offspring resulting from the interbreeding of two genetically distinct taxa. It has been documented in over 10% of wild animals, and at least in 34 cases for Artic marine mammals. In Otariids, intergeneric hybridization has been reported though neither confirming it through genetic analyses nor presenting evidence of fertile offspring. In this study, we report the finding of a hybrid adult female between a South American fur seal (Arctocephalus australis) and a South American sea lion (Otaria byronia), and its offspring, a male pup, in Uruguay. Further based on morphological constraints and breeding seasons, sex-biased hybridization between the two species is hypothesized. Morphological and genetic (nuclear and mitochondrial) results confirm de hybrid nature of the female-pup pair. Here we discuss a genetic dilution effect, considering other hybridization events must be occurring, and how isolation mechanisms could be circumvented. Moreover, the results obtained from stable isotope analysis suggest feeding habits may be a trait transmitted maternally, leading to consider broader issues regarding hybridization as an evolutionary innovation phenomenon. PMID- 26994862 TI - "Medication utilization...the great multiplier!". PMID- 26994863 TI - Lost in the archive. PMID- 26994865 TI - Implementation of the 2011 Reimbursement Act in Poland: Desired and undesired effects of the changes in reimbursement policy. AB - The Act of 12 May 2011 on the Reimbursement of Medicines, Foodstuffs Intended for Particular Nutritional Uses and Medical Devices constitutes a major change of the reimbursement policy in Poland. The main aims of this Act were to rationalize the reimbursement policy and to reduce spending on reimbursed drugs. The Act seems to have met these goals: reimbursement policy (including pricing of reimbursed drugs) was overhauled and the expenditure of the National Health Fund on reimbursed drugs saw a significant decrease in the year following the Act's introduction. The annual savings achieved since then (mainly due to the introduction of risk sharing schemes), have made it possible to include new drugs into the reimbursement list and improve access to innovative drugs. However, at the same time, the decrease in prices of reimbursed drugs, that the Act brought about, led to an uncontrolled outflow of some of these drugs abroad and shortages in Poland. This paper analyses the main changes introduced by the Reimbursement Act and their implications. Since the Act came into force relatively recently, its full impact on the reimbursement policy is not yet possible to assess. PMID- 26994866 TI - Stuck in the middle?: A perspective on ongoing pro-competitive reforms in Dutch mental health care. AB - Pro-competitive reforms have been implemented in many Western healthcare systems, of which the Netherlands is a prominent example. While the pro-competitive reforms in the Dutch specialized care sector have drawn considerable academic attention, mental health care is often excluded. However, in line with other segments of specialized care, pro-competitive legislation has formed the core of mental health care reforms, albeit with several notable differences. Ever since mental health services were included in the Health Insurance Act in 2008, the Dutch mental healthcare sector has been in an ongoing state of reform. Numerous major and minor adaptations have continuously altered the services covered by the basic insurance package, the actors responsible for providing and contracting care, and definitions and measurements of quality. Most notably, insurers and municipalities, which are responsible for selectively contracting those providers that offer high value-for-money, seem insensitive to quality aspects. The question whether the Dutch mental health sector has inherited the best or the worst of a competitive and non-competitive system lingers and international policy makers contemplating reforming their mental health sector should take note. PMID- 26994867 TI - Dynamic Chemistry of Disulfide Terminated Oligonucleotides in Duplexes and Double Crossover Tiles. AB - Designed nanostructures formed by self-assembly of multiple DNA strands suffer from low stability at elevated temperature and under other denaturing conditions. Here, we propose a method for covalent coupling of DNA strands in such structures by the formation of disulfide bonds; this allows disassembly of the structure under reducing conditions. The dynamic chemistry of disulfides and thiols was applied to crosslink DNA strands with terminal disulfide modifications. The formation of disulfide-linked DNA duplexes consisting of three strands is demonstrated, as well as a more-complex DNA double-crossover tile. All the strands in the fully disulfide-linked structures are covalently and geometrically interlocked, and it is demonstrated that the structures are stable under heating and in the presence of denaturants. Such a reversible system can be exploited in applications where higher DNA stability is needed only temporarily, such as delivery of cargoes to cells by DNA nanostructures. PMID- 26994868 TI - Perspectives on reticular pseudodrusen in age-related macular degeneration. AB - Drusen have been considered the clinical hallmark of age-related macular degeneration (AMD). Reticular pseudodrusen (RPD), although first described about 25 years ago, have only been recently recognized as an additional clinical phenotype of AMD with distinct characteristics on multimodal imaging and significant impact on visual function. Eyes with RPD are at greater risk of progression to advanced AMD when compared with eyes with drusen only. RPD can also occur in the absence of drusen. Unlike features external to the retinal pigment epithelium that have received most attention in AMD, evidence suggests that RPD are associated with changes internal to the RPE. Therefore, new avenues regarding the pathogenesis of AMD are highlighted by these recent observations. We summarize the current knowledge regarding the histology, imaging, and functional changes in eyes with RPD in AMD and offer concepts of future research for the AMD community to discuss. PMID- 26994869 TI - Clinical challenge: An orbital Hickam's dictum. AB - A 53-year-old man with hyperthyroidism presented with asymmetric proptosis and diplopia. Thyroid-stimulating immunoglobulin was elevated, suggesting active thyroid eye disease. Imaging of the orbits revealed enlargement of the extraocular muscles, including irregular enlargement of the left lateral rectus muscle. Biopsy of the lateral rectus muscle demonstrated infiltration of the muscle with Bcl-2 positive B lymphocytes consistent with chronic lymphocytic leukemia (CLL). Evaluation for systemic lymphoproliferative disease was negative. The patient was treated with orbital radiotherapy at specific dosages for both TED and CLL. He responded well to therapy with a reduction in proptosis and diplopia and no evidence of recurrent CLL. PMID- 26994870 TI - Orbital inflammation: Biopsy first. AB - Orbital inflammation is a response of the immune system and not a diagnosis in itself. Exposing the underlying disease introduces a labyrynthine challenge owing to the broad array of possible causes ranging from infectious, structural, autoimmune, idiopathic to neoplastic origin. In this regard, and despite its unkown etiology, idiopathic orbital inflammation (IOI) intrinsically is a genuine diagnostic entity. Where clinical and radiological findings of an orbital inflammatory mass are inconclusive, pathological examination of the tissue biopsy obtained by minimally invasive approach and local anesthesia-is advocated to work towards a diagnosis in a most timely and effective manner. A corticosteroid response can be observed in most orbital disorders with lymphocytic components, including IOI, and, accordingly, constitutes a paradoxical and weak tool to identify the diagnosis in orbital inflammation. PMID- 26994872 TI - Protection against MPP(+)-induced neurotoxicity in SH-SY5Y cells by tormentic acid via the activation of PI3-K/Akt/GSK3beta pathway. AB - The cause of Parkinson's disease (PD) could be ascribed to the progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta, and thus molecules with neuroprotective ability may have therapeutic value against PD. In the current study, the neuroprotective effects and underlying mechanisms of tormentic acid (TA), a naturally occurring triterpene extracted from medicinal plants such as Rosa rugosa and Potentilla chinensis, were evaluated in a widely used cellular PD model in which neurotoxicity was induced by MPP(+) in cultured SH-SY5Y cells. We found that TA at 1-30 MUM substantially protected against MPP(+)-induced neurotoxicity, as evidenced by the increase in cell viability, decrease in lactate dehydrogenase release and the reduction in apoptotic nuclei. Moreover, TA effectively inhibited the elevated intracellular accumulation of reactive oxygen species as well as Bax/Bcl-2 ratio caused by MPP(+). Most importantly, TA markedly reversed the inhibition of protein expression of phosphorylated Akt (Ser 473) and phosphorylated GSK3beta (Ser 9) caused by MPP(+). LY294002, the specific inhibitor of PI3-K, significantly abrogated the up regulated phosphorylated Akt and phosphorylated GSK3beta offered by TA, suggesting that the neuroprotection of TA was mainly dependent on the activation of PI3-K/Akt/GSK3beta signaling pathway. The results taken together indicate that TA may be a potential candidate for further preclinical study aimed at the prevention and treatment of PD. PMID- 26994871 TI - Intraocular foreign bodies: A review. AB - Intraocular foreign body injuries may result in a wide range of intraocular pathology and visual outcomes based on the mechanism of injury, type of foreign body, and subsequent complications. We have reviewed the literature to describe the epidemiology and mechanisms of such injuries; types of foreign bodies; imaging tools for diagnosis; current trends in management, presurgical, and surgical interventions; as well as visual prognosis and potential complications. The purpose of this review is to familiarize clinicians with the recent advances in diagnosis and management of such injuries. PMID- 26994873 TI - Role of Wnt/beta-catenin in the tolerance to focal cerebral ischemia induced by electroacupuncture pretreatment. AB - Previous studies have demonstrated that pretreatment with electroacupuncture (EA) elicits rapid tolerance to focal cerebral ischemia and that Wnt/beta-catenin plays an essential role in cell survival and proliferation. In the present study, we investigated the role of Wnt/beta-catenin in EA pretreatment-induced neuroprotection. Two hours after EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h. Neuronal survival, cell apoptosis, and the Garcia neurological deficit scores were evaluated 24 h after reperfusion. Moreover, learning and memory deficits were assessed 24 h after reperfusion using the Morris water maze test. Finally, the expression of beta-catenin and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were investigated in the presence and absence of the Wnt/beta-catenin antagonist Dickkopf-1 (Dkk-1), which was administered 30 min before MCAO. We observed that EA pretreatment significantly increased the neuronal expression of beta-catenin in the hippocampus 24 h after reperfusion. Moreover, EA pretreatment improved the neurological outcomes, decreased neuronal loss, inhibited apoptosis, and reversed learning and memory deficits following reperfusion. These beneficial effects of EA were attenuated by Dkk-1, which effectively reversed the expression of beta-catenin. Furthermore, the administration of a Wnt/beta-catenin agonist upregulated the expression of beta-catenin and the Bcl-2/Bax ratio. These results suggest that Wnt/beta-catenin plays a role in the protective effects of EA pretreatment against cerebral ischemia, thus providing evidence of a novel mechanism underlying EA-pretreatment-induced rapid tolerance to focal cerebral ischemia. PMID- 26994875 TI - Engineering EMT using 3D micro-scaffold to promote hepatic functions for drug hepatotoxicity evaluation. AB - Accompanied by decreased hepatic functions, epithelial-mesenchymal transition (EMT) was observed in two dimensional (2D) cultured hepatocytes with elongated morphology, loss of polarity and weakened cell-cell interaction, while upgrading to 3D culture has been considered as significant improvement of its 2D counterpart for hepatocyte maintenance. Here we hypothesize that 3D culture enhances hepatic functions through regulating the EMT status. Biomaterial engineered EMT was achieved by culturing HepaRG as 3D spheroids (SP-3D) or 3D stretched cells (ST-3D) in non-adherent and adherent micro-scaffold respectively. In SP-3D, constrained EMT of HepaRG, a hepatic stem cell line, as represented by increased epithelial markers and decreased mesenchymal markers, was echoed by improved hepatic functions. To investigate the relationship between EMT status and hepatic functions, time-series RNA-Seq and gene network analysis were used for comparing different cell culture models, which identified histone deacetylases (HDACs) as key mediating factors. Protein analysis confirmed that high HDAC activity was correlated with high expression of Cadherin-1 (CDH1) and hepatic function genes, which were decreased upon HDAC inhibitor treatment in SP 3D, suggesting HDACs may play positive role in regulating EMT and hepatic functions. To illustrate the application of 3D micro-scaffold culture in drug safety evaluation, hepatotoxicity and metabolism assays of two hepatotoxins (i.e. N-acetyl-p-aminophenol and Doxorubicin) were performed and SP-3D showed more biomimetic toxicity response, indicating regulation of EMT as a vital consideration in designing 3D hepatocyte culture configuration. PMID- 26994874 TI - Thailandepsin A-loaded and octreotide-functionalized unimolecular micelles for targeted neuroendocrine cancer therapy. AB - Due to the overexpression of somatostatin receptors in neuroendocrine (NE) cancers, drug nanocarriers conjugated with somatostatin analogs, such as octreotide (OCT), for targeted NE cancer therapy may offer increased therapeutic efficacies and decreased adverse effects. In this study, OCT-functionalized unimolecular micelles were prepared using individual hyperbranched polymer molecules consisting of a hyperbranched polymer core (Boltorn((r)) H40) and approximately 25 amphiphilic polylactide-poly(ethlyene glycol) (PLA-PEG) block copolymer arms (H40-PLA-PEG-OCH3/OCT). The resulting micelles, exhibiting a uniform core-shell shape and an average hydrodynamic diameter size of 66 nm, were loaded with thailandepsin-A (TDP-A), a relatively new naturally produced histone deacetylase (HDAC) inhibitor. In vitro studies using flow cytometry and confocal laser scanning microscopy (CLSM) demonstrated that OCT conjugation enhanced the cellular uptake of the unimolecular micelles. Consequently, TDP-A-loaded and OCT conjugated micelles exhibited the highest cytotoxicity and caused the highest reduction of NE tumor markers. Finally, the in vivo studies on NE cancer bearing nude mice demonstrated that TDP-A-loaded and OCT-conjugated micelles possessed superior anticancer activity in comparison with other TDP-A formulations or drug alone, while showing no detectable systemic toxicity. Thus, these TDP-A-loaded and OCT-conjugated micelles offer a promising approach for targeted NE cancer therapy. PMID- 26994876 TI - A critical review of cell culture strategies for modelling intracortical brain implant material reactions. AB - The capacity to predict in vivo responses to medical devices in humans currently relies greatly on implantation in animal models. Researchers have been striving to develop in vitro techniques that can overcome the limitations associated with in vivo approaches. This review focuses on a critical analysis of the major in vitro strategies being utilized in laboratories around the world to improve understanding of the biological performance of intracortical, brain-implanted microdevices. Of particular interest to the current review are in vitro models for studying cell responses to penetrating intracortical devices and their materials, such as electrode arrays used for brain computer interface (BCI) and deep brain stimulation electrode probes implanted through the cortex. A background on the neural interface challenge is presented, followed by discussion of relevant in vitro culture strategies and their advantages and disadvantages. Future development of 2D culture models that exhibit developmental changes capable of mimicking normal, postnatal development will form the basis for more complex accurate predictive models in the future. Although not within the scope of this review, innovations in 3D scaffold technologies and microfluidic constructs will further improve the utility of in vitro approaches. PMID- 26994877 TI - Multifunctional aptamer-based nanoparticles for targeted drug delivery to circumvent cancer resistance. AB - By its unique advantages over traditional medicine, nanomedicine has offered new strategies for cancer treatment. In particular, the development of drug delivery strategies has focused on nanoscale particles to improve bioavailability. However, many of these nanoparticles are unable to overcome tumor resistance to chemotherapeutic agents. Recently, new opportunities for drug delivery have been provided by oligonucleotides that can self-assemble into three-dimensional nanostructures. In this work, we have designed and developed functional DNA nanostructures to deliver the chemotherapy drug doxorubicin (Dox) to resistant cancer cells. These nanostructures have two components. The first component is a DNA aptamer, which forms a dimeric G-quadruplex nanostructure to target cancer cells by binding with nucleolin. The second component is double-stranded DNA (dsDNA), which is rich in -GC- base pairs that can be applied for Dox delivery. We demonstrated that Dox was able to efficiently intercalate into dsDNA and this intercalation did not affect the aptamer's three-dimensional structure. In addition, the Aptamer-dsDNA (ApS) nanoparticle showed good stability and protected the dsDNA from degradation in bovine serum. More importantly, the ApS&Dox nanoparticle efficiently reversed the resistance of human breast cancer cells to Dox. The mechanism circumventing doxorubicin resistance by ApS&Dox nanoparticles may be predominantly by cell cycle arrest in S phase, effectively increased cell uptake and decreased cell efflux of doxorubicin. Furthermore, the ApS&Dox nanoparticles could effectively inhibit tumor growth, while less cardiotoxicity was observed. Overall, this functional DNA nanostructure provides new insights into the design of nanocarriers to overcome multidrug resistance through targeted drug delivery. PMID- 26994878 TI - Index-finger pointing in generalized tonic-clonic seizures. AB - OBJECTIVE: Most patients with localization-related epilepsy (LRE) and genetic generalized epilepsy (GGE) are classified based on semiology and video-EEG, but both features occasionally fail to provide a definitive diagnosis. Several reliable lateralizing signs have been described, although hand and finger posturing has received little attention. We sought to investigate the frequency of index-finger pointing (IFP) during generalized motor convulsions as a lateralizing semiology in LRE. METHODS: We retrospectively analyzed 98 videos of generalized convulsions in 64 consecutive patients who were admitted for diagnostic video-EEG (vEEG). Demographics were recorded, and IFP ipsilateral, contralateral, and bilateral to vEEG ictal correlate was compared between LRE, GGE, and nonepileptic attacks (NEAs). The angle of IFP was measured to quantify the mean degree of IFP in "pointers" versus "nonpointers". Statistical analysis was completed using JMP 9.0. RESULTS: Index-finger pointing was more common in epileptic GTC seizures than in convulsive NEAs (83.6% vs 12.0%; p<0.001) and was more common in LRE compared with GGE (96% vs 56.6%; p<=0.001). The frequency of contralateral, ipsilateral, or bilateral IFP did not differ between LRE and GGE. The average angle at the MCP joint in "pointers" was 35.8 degrees (SD 22.0 degrees ) and in "nonpointers" 3.0 degrees (SD 7.2 degrees ). SIGNIFICANCE: This is the first study to examine hand and finger postures as a clinical sign to help classify epilepsy type. The presence of IFP was more common in patients with LRE than in patients with GGE and very rarely occurred in NEA. Index-finger pointing and other hand semiologies are potentially quantifiable localizing signs to aid in the characterization of patients with GTC seizures. PMID- 26994879 TI - Impact of periictal nurse interventions on postictal generalized EEG suppression in generalized convulsive seizures. AB - OBJECTIVES: The objective of this study was to determine the impact of periictal nurse interventions on postictal generalized EEG suppression (PGES) in generalized convulsive seizures (GCS). METHODS: We retrospectively reviewed the video-EEG recordings of patients during long-term video-EEG monitoring. We compared the duration of seizures, seizure phases (tonic, clonic, and tonic clonic phases), and the occurrence and duration of postictal generalized EEG suppression (PGES) in patients with and without periictal interventions (e.g., oxygen administration, suctioning, and repositioning). Statistical analyses were performed to determine the association between the seizure-related variables and the periictal interventions. RESULTS: A total of 109 patients with 150 GCS were included in the study. Periictal interventions were provided in 122 GCS, of which, ictal administration of oxygen was provided in 29 GCS. The duration of PGES was significantly shortened in GCS with interventions when compared with those without interventions (p=0.003). However, the ictal administration of oxygen, assessed as an independent variable, did not influence the occurrence or duration of PGES. CONCLUSION: Periictal interventions significantly shortened the duration of PGES, and may, as a consequence, reduce the risk of SUDEP. However, ictal administration of oxygen did not influence the occurrence or duration of PGES. PMID- 26994880 TI - Relevant optical properties for direct restorative materials. AB - OBJECTIVES: To evaluate relevant optical properties of esthetic direct restorative materials focusing on whitened and translucent shades. METHODS: Enamel (E), body (B), dentin (D), translucent (T) and whitened (Wh) shades for E (WhE) and B (WhB) from a restorative system (Filtek Supreme XTE, 3M ESPE) were evaluated. Samples (1 mm thick) were prepared. Spectral reflectance (R%) and color coordinates (L*, a*, b*, C* and h degrees ) were measured against black and white backgrounds, using a spectroradiometer, in a viewing booth, with CIE D65 illuminant and d/0 degrees geometry. Scattering (S) and absorption (K) coefficients and transmittance (T%) were calculated using Kubelka-Munk's equations. Translucency (TP) and opalescence (OP) parameters and whiteness index (W*) were obtained from differences of CIELAB color coordinates. R%, S, K and T% curves from all shades were compared using VAF (Variance Accounting For) coefficient with Cauchy-Schwarz inequality. Color coordinates and optical parameters were statistically analyzed using one-way ANOVA, Tukey's test with Bonferroni correction (alpha=0.0007). RESULTS: Spectral behavior of R% and S were different for T shades. In addition, T shades showed the lowest R%, S and K values, as well as the highest T%, TP an OP values. In most cases, WhB shades showed different color and optical properties (including TP and W*) than their corresponding B shades. WhE shades showed similar mean W* values and higher mean T% and TP values than E shades. SIGNIFICANCE: When using whitened or translucent composites, the final color is influenced not only by the intraoral background but also by the color and optical properties of multilayers used in the esthetic restoration. PMID- 26994881 TI - Palinacousis secondary to brain damage from methotrexate. PMID- 26994882 TI - Mucocutaneous leishmaniasis. PMID- 26994883 TI - Gene mutation-based and specific therapies in precision medicine. AB - Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide-ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses. PMID- 26994884 TI - The Prevalence of Latent Trigger Points in Lower Limb Muscles in Asymptomatic Subjects. AB - BACKGROUND: Latent trigger points (LTrPs) are prevalent in persons with musculoskeletal pain. Because they could be present in healthy persons, it is necessary to evaluate the prevalence of LTrPs in asymptomatic subjects. OBJECTIVES: To assess the prevalence of LTrPs in lower limb muscles, to evaluate the relationship between LTrP prevalence, gender, and leg dominance, and to determine intra-rater reliability for the diagnosis of LTrPs. DESIGN: Cross sectional study. SETTING: University community. PATIENTS: A total of 206 asymptomatic subjects (113 women and 93 men, aged 23.2 +/- 5.2 years). INTERVENTION: Not applicable. MAIN OUTCOMES MEASURES: The prevalence of the LTrPs located in the gastrocnemius, soleus, peroneus longus, peroneus brevis, tibialis anterior, extensor digitorum longus, flexor digitorum longus, rectus femoris, vastus medialis, and vastus lateralis was studied, using the diagnosis criteria recommended by Simons, Travell, and Simons. The pressure pain threshold was also evaluated. RESULTS: Of the 206 subjects evaluated, 166 (77.7%; 95% confidence interval [CI], 72-83.4) were found to have at least one LTrP in the lower limb muscles. The average number of LTrPs found per individual was 7.5 +/- 7.7. The prevalence in each muscle group ranged from 19.9% (95% CI, 14.4-25.4) to 37.4% (95% CI, 30.8-44), with gastrocnemius LTrPs being the most prevalent. Women had more LTrPs (9.6 +/- 7.8) than did men (4.9 +/- 6.6) (P < .01). No relationship was found between the LTrPs and leg dominance (P > .05). The most prevalent diagnosis criteria were the presence of a taut band and a tender spot (98%-100%); the local twitch response was the least prevalent diagnosis criteria (0%-3.5%). Intra-rater reliability was excellent for all the diagnosis criteria in all the muscles evaluated (kappa = 0.762-1), except for the jump sign and the referred pain in several LTrPs. CONCLUSION: LTrPs were prevalent in the lower limb muscles of asymptomatic subjects. Women have more LTrPs than do men. No differences in LTrP prevalence were found between sides. The presence of the taut band and the tender spot were the most prevalent and reliable diagnosis criteria. It is necessary to determine if the evaluation of LTrPs in the lower limb muscles of asymptomatic subjects has clinical relevance. LEVEL OF EVIDENCE: IV. PMID- 26994885 TI - Effect of Focal Muscle Vibration on Calf Muscle Spasticity: A Proof-of-Concept Study. AB - BACKGROUND: Focal vibration has been studied for its ability to reduce spasticity in patients with upper motor neuron lesions, but adequate stimulation parameters remain unclear. Focal muscle vibration with adequate parameters may facilitate gait rehabilitation in patients with lower limb spasticity. OBJECTIVE: To determine focal muscle vibration parameters that effectively inhibit the H-reflex of the gastrocnemius in healthy subjects. DESIGN: A proof-of-concept exploratory study. SETTING: University hospital laboratory. SUBJECTS: Thirteen healthy volunteers. METHODS: Focal muscle vibrations of 40, 80, and 120 Hz and amplitudes of 0.1, 0.3, and 0.5 mm were tested on the calf muscles of 10 healthy subjects, respectively. The H-reflex and M-response were recorded baseline, during vibration, and after vibration for each stimulation parameter. The mean vibratory inhibition index (VII) during vibration, the maximum amplitude of the H-reflex and M-response (Hmax and Mmax), minimal onset latency of the H-reflex, and the ratio of Hmax to Mmax (HMR) at each time point were measured. RESULTS: No significant difference was found among mean VIIs at 40, 80, and 120 Hz in the healthy subjects. However, a relatively consistent reduction of Hmax and HMR was observed at 80 Hz. Mean VIIs at 0.3 and 0.5 mm were significantly lower than that at 0.1 mm (P < .001). CONCLUSION: This study suggests that focal muscle vibration may be an adjuvant therapy during gait rehabilitation in patients with calf muscle spasticity. Focal vibration at 80 Hz and 0.3 mm amplitude applied to the gastrocnemius effectively inhibits the segmental reflex pathway. A future clinical trial on this topic is warranted. LEVEL OF EVIDENCE: II. PMID- 26994887 TI - Development of Metronidazole-Loaded Colon-Targeted Microparticulate Drug Delivery System. AB - BACKGROUND: Crohn's disease and ulcerative colitis are the main autoimmune inflammatory bowel diseases. Metronidazole is the most commonly used drug for the treatment of Crohn's disease. However, the pharmacokinetic profile of this drug indicates that the largest amount of the drug is absorbed from the upper part of the intestines and very little concentration of the drugs reaches the colon.Objectives: The aim of this investigation was to formulate metronidazole loaded microspheres for the efficient therapy of inflammatory bowel diseases.Material and Methods: Microspheres were prepared using the emulsification-solvent evaporation method. The effect of Eudragit S100 concentration and the ratio of liquid paraffin (light: heavy) on percentage yield, particle size, morphology, drug encapsulation and in vitro drug release was examined. Drug-polymer interaction was investigated using Fourier Transformed Infrared Spectroscopy (FTIR). RESULTS: The results showed that the particle had good flow properties, encapsulation efficiency (56.11 ?} 1.51-81.02 ?} 2.14%)and cumulative drug release (64.14 ?} 0.83-79.69 ?} 2.45%) in a phosphate buffer (pH 6.8) after 10 h of the dissolution study.An increased particle size was observed with an increasing polymer concentration. It was observed that the Eudragit had a positive effect on the drug encapsulation and negative effect on drug release. Aggregation of drug-polymer droplets was observed at a lower level of magnesium stearate during microsphere preparation. The results of FTIR spectroscopy revealed the absence of any drug-polymer interactions. However, slight peak shifting and suppression in peak height was observed.This might be due to the minor ionic interactions. The microspheres were discrete, spherical and free flowing. The spherical shape of the microspheres was confirmed from SEM photomicrographs. The developed microspheres showed a controlled drug release and were found to follow Higuchi's model. The release mechanism of metronidazole from the microspheres was Fickian diffusion without swelling. CONCLUSIONS: The results suggest that the developed microspheres could enhance drug entrapment, and inflect the drug release. PMID- 26994886 TI - Influence of Polymer Type on the Physical Properties and Release Profile of Papaverine Hydrochloride From Hard Gelatin Capsules. AB - BACKGROUND: The capsule is one of the most important solid dosage forms in the pharmaceutical industry. It is easier and faster to produce than a tablet, because it requires fewer excipients. Generally, capsules are easy to swallow and mask any unpleasant taste of the substances used while their release profiles can be easily modified. Papaverine hydrochloride was used as a model substance to show different release profiles using different excipients. OBJECTIVES: The main aim of the study was to analyze the impact of using different polymers on the release profile of papaverine hydrochloride from hard gelatin capsules. MATERIAL AND METHODS: Six series of hard gelatin capsules containing papaverine hydrochloride as a model drug and different excipients were made. Then, the angle of repose, flow rate, mass flow rate and volume flow rate of the powders used for capsule production were analyzed. The uniform weight and disintegration time of the capsules were studied. The dissolution study was performed in a basket apparatus, while the amount of papaverine hydrochloride released was determined spectrophotometrically at 251 nm. RESULTS: Only one formula of powder had satisfactory flow properties, while all formulas had good Hausner ratios. The best properties were from powder containing polyvinylpyrrolidone 10k. The disintegration time of capsules varied from 1:30 min to 2:00 min. As required by Polish Pharmacopoeia X, 80% of the active substance in all cases was released within 15 minutes. The capsules with polyvinylpyrrolidone 10k were characterized by the longest release. On the other hand, capsules containing microcrystalline cellulose had the fastest release profile. CONCLUSIONS: Using 10% of different polymers, without changing the other excipients, had a significant impact on the physical properties of the powders and papaverine hydrochloride release profile. The two most preferred capsule formulations contained either polyvinylpyrrolidone 10k or microcrystalline cellulose. PMID- 26994888 TI - Effect of Calcium Chloride on Release Behavior of Babul (Acacia nilotica) gum Microbeads. AB - BACKGROUND: Oral delivery of drugs is the most common method, but due to the inability of drugs to restrain and localize in the gastro-intestinal tract, oral administration of drugs in conventional dosage forms have short-term limitations. Carrier technology may provide many approaches for the delivery of drugs by coupling the drug to a carrier particle, such as Microspheres, nanoparticles and liposomes, which modulate the release and absorption characteristics of the drug. OBJECTIVES: The aim of this study was to prepare Diclofenac sodium microspheres using a natural polymer and show the effect of calcium chloride on the release behavior of microspheres. The microspheres of Diclofenac sodium were successfully developed by ionic gelation technique using natural polymer babul gum with sodium alginate. MATERIAL AND METHODS: Diclofenac Sodium was received as a gift sample from Aegis Pharmaceuticals Pvt. Ltd., Roorkee. Acacia nilotica gum was purchased from Ghaziabad and purification was done in the laboratory. All other excipients used analytical grade method. The microspheres of diclofenac sodium were prepared by Ionic gelation method using a natural polimer, i.e. Acacia nilotica. Calcium chloride (5% solution) was used as a cross-linking agent. In this research article all the data was presented as averages and standard deviations. RESULTS: Five formulations were successfully prepared, i.e. F1, F2, F3, F4 and F5. All the formulations were evaluated for micromeritic properties, particle size analysis, percentage yield, drug content, drug entrapment efficacy, percent moisture loss, swelling index and in vitro dissolution studies. The size of the microspheres varied between 14.55 +/- 0.29 to 20.18 +/- 0.15 MUm and as high as 81.51 +/- 0.14% entrapment efficiency for babul gum was obtained. CONCLUSIONS: Batch F1 and F5 was found to release the drug 91.35% and 75.48% respectively for 6 hrs. The formulations were found to be effective in providing controlled release of drug for a prolonged period of time. PMID- 26994889 TI - [The Use of Synthetic Polymers (Superdisintegrants) in Technology Tablets Containing Ethanol Dry Extract from Asparagus officinalis]. AB - BACKGROUND: Dry extracts are now frequently used in medicine as an alternative to synthetic drugs. In the case of tablet technology with dry plant extracts, the proper selection of disintegrants (superdisintegrants) is particularly important. Objectives. The aim of this study was to evaluate the usefulness of the polymers constituting superdisintegrants (Vivasol(r), Vivastar(r), Polyplasdone XL) in uncoated tablet formulation of alcoholic extracted from Asparagus officinalis. MATERIAL AND METHODS: Dry the ethanol extract of Asparagus officinalis, Vivasol(r), Vivastar(r), Vivapur(r), Kollidon VA64, Polyplasdone XL, magnesium stearate. Direct compression. Paddle method was carried out to study pharmacopoeial parameters and pharmaceutical availability. The calculation of equivalency factors: similarity [f2] and the difference [f1]. Approximation results. RESULTS: Tablets brownish-green, with a smooth and uniform surface, without stains, chipping and damage. The determined average weight of the tablets compiled with the standards. The test friability and crushing strength revealed that the most mechanically strong tablets contained Vivasol, Vivastar, Polyplasdone XL. These tablets also have a longer disintegration and dissolution time compared with tablets containing only Vivasol. These differences are also confirmed by the calculated f2 and f1. CONCLUSIONS: The addition of a mixture of Polyplasdone XL and Vivastar to Vivasol significantly increases the mechanical strength of the tablets (crushing strength, resistance to crushing). The addition of a mixture of Polyplasdone XL and Vivastar to Vivasol paradoxically increases the disintegration time of tablets (11.1 min). Single superdisintegrant breaks up the tablet more effectively than a mixture of superdisintegrants. PMID- 26994890 TI - [Metal-Organic Frameworks: A New Class of Mesoporous Materials and Potential Possibilities of Their Use in Pharmaceutical Technology]. AB - Metal-organic frameworks (MOFs) belong to the new class of mesoporous, hybrid materials composed of metal ions and organic binding ligands. Their unique features: wide range of chemical building components, which enables obtaining biocompatible materials, and high surface area and loading capacity, make them promising drug delivery vehicles for therapeutic agents. The ability to tune their structures and porosities provides better adjustment for adsorbed drug molecule. Moreover, MOFs functionalized with ligands or antibodies can be used in cancer targeted therapy. Through the incorporation of paramagnetic metal ions into the structure, MOFs are suited to serve as magnetic resonance imaging (MRI) contrast agents. Combining drug delivery ability with imaging properties of MOFs indicates their potential use as theranostic agents and makes possible monitoring drug delivery within the body after administration in the real time. The aim of the present study is to characterize a new class of compounds and to present potential possibilities of their use as excipients in pharmaceutical technology . PMID- 26994891 TI - [The Use of Polymers for Intraocular Lenses in Cataract Surgery]. AB - According to the World Health Organization, cataract remains the leading cause of the curable visual impairment worldwide. Cataract can only be cured by surgery during which the cloudy lens is replaced with an artificial intraocular lens. It is one of the most common surgeries being performed worldwide. There are age related, congenital, traumatic and metabolic types of cataract which have been distinguished. Age-related cataract is the most common one and it affects people over 60 with the greatest frequency. In reference to patients whose cornea does not fulfill the requirements for a standard refractive surgery, the number of refractive intraocular lens replacement is increasing. Manufacturers aim to enhance materials in order to minimize surgical complication while increasing the patient's eyesight. The increase in average lifespan along with patients' expectations stimulate competition among manufacturers who bring new products and solutions into to the market. There is an augmented demand for premium lenses such as toric, multifocal or accommodating. These lenses bring patients the promise of life without the need for wearing glasses. As far as the main materials used in the production of intraocular lens are concerned, there are hydrophobic, hydrophilic, acrylic and silicone lenses in use. In this paper the author discusses characteristics as well as advantages and disadvantages of the above-mentioned materials. The associated surgical complications and the new areas of development regarding the materials used in lenses manufacturing are also examined. PMID- 26994892 TI - Emergency inguinal hernia repair under local anesthesia: a 5-year experience in a teaching hospital. AB - BACKGROUND: Local anesthesia (LA) has been reported to be the best choice for elective open inguinal hernia repair because it is cost efficient, with less post operative pain and enables more rapid recovery. However, the role of LA in emergency inguinal hernia repair is still controversial. The aim of this study is to investigate the safety and effectiveness of LA in emergency inguinal hernia repair. METHODS: All patients underwent emergency inguinal hernia repair in our hospital between January 2010 and April 2014 were analyzed retrospectively in this study. Patients were divided into LA and general anesthesia (GA) group according to the general conditions of the patients decided by anesthetists and surgeons. The outcome parameters measured included time to recovery, early and late postoperative complications, total expense and recurrence. RESULTS: This study included a total of 90 patients from 2010 to 2015. 32 patients (35.6%) were performed under LA, and 58 (64.4%) were performed under GA. LA group has less cardiac complications (P = 0.044) and respiratory complications (P = 0.027), shorter ICU stay (P = 0.035) and hospital stay (P = 0.001), lower cost (P = 0.000) and faster recovery time (P = 0.000) than GA group. CONCLUSION: LA could provide effective anesthesia and patient safety in emergency inguinal hernia repair. PMID- 26994894 TI - Combined procedure of cesarean delivery and preperitoneal mesh repair for inguinal hernia: An initial experience. AB - BACKGROUND: Combined surgery for cesarean delivery and preperitoneal mesh repair for inguinal hernia has not been previously reported. OBJECTIVES: Our aim was to describe the method and to present the results of this simultaneous surgery through a single incision. METHODS: From 2012 to 2014, 15 patients underwent cesarean delivery combined with preperitoneal mesh repair for inguinal hernia. All patient characteristics and perioperative findings were recorded. RESULTS: Among 15 patients, 13 had unilateral inguinal hernias and two had bilateral hernias. The mean times spent for unilateral and bilateral hernias were 35.8 minutes (range, 30-45 minutes) and 67.5 minutes (range, 65-70 minutes), respectively. Direct and indirect hernias were present in one and 15 patients, respectively. One patient had mixed hernia. No significant complication was observed perioperatively. Hospital stay ranged from 1 day to 3 days (mean, 1.87 days), and all patients were discharged without any problem. No recurrence was found during the follow-up periods. CONCLUSION: Single anesthesia, single incisional scar, and single hospitalization are the major advantages of this simultaneous approach of cesarean delivery and preperitoneal mesh repair for inguinal hernia. Our analysis suggests that this combined procedure can be performed safely in selected cases. PMID- 26994893 TI - Recovery of Salivary Function: Contralateral Parotid-sparing Intensity-modulated Radiotherapy versus Bilateral Superficial Lobe Parotid-sparing Intensity modulated Radiotherapy. AB - AIMS: To establish whether there is a difference in recovery of salivary function with bilateral superficial lobe parotid-sparing intensity-modulated radiotherapy (BSLPS-IMRT) versus contralateral parotid-sparing IMRT (CLPS-IMRT) in patients with locally advanced head and neck squamous cell cancers. MATERIALS AND METHODS: A dosimetric analysis was carried out on data from two studies in which patients received BSLPS-IMRT (PARSPORT II) or CLPS-IMRT (PARSPORT). Acute (National Cancer Institute, Common Terminology Criteria for adverse events - NCI CTCAEv3.0) and late (Late Effects of Normal Tissue- subjective, objective, management analytical - LENTSOMA and Radiation Therapy Oncology Group) xerostomia scores were dichotomised: recovery (grade 0-1) versus no recovery (>=grade 2). Incidence of recovery of salivary function was compared between the two techniques and dose response relationships were determined by fitting dose-response curves to the data using non-linear logistic regression analysis. RESULTS: Seventy-one patients received BSLPS-IMRT and 35 received CLPS-IMRT. Patients received 65 Gy in 30 fractions to the primary site and involved nodal levels and 54 Gy in 30 fractions to elective nodal levels. There were significant differences in mean doses to contralateral parotid gland (29.4 Gy versus 24.9 Gy, P < 0.005) and superficial lobes (26.8 Gy versus 30.5 Gy, P = 0.02) for BSLPS and CLPS-IMRT, respectively. Lower risk of long-term >=grade 2 subjective xerostomia (LENTSOMA) was reported with BSLPS-IMRT (odds ratio 0.50; 95% confidence interval 0.29-0.86; P = 0.012). The percentage of patients who reported recovery of parotid saliva flow at 1 year was higher with BSLPS-IMRT compared with CLPS-IMRT techniques (67.1% versus 52.8%), but the difference was not statistically significant (P = 0.12). For the whole parotid gland, the tolerance doses, D50, were 25.6 Gy (95% confidence interval 20.6-30.5), k = 2.7 (0.9-4.5) (CLPS-IMRT) and 28.9 Gy (26.1-31.9), k = 2.4 (1.4-3.4) (BSLPS-IMRT). For the superficial lobe, D50 were similar: BSLPS IMRT 23.5 Gy (19.3-27.6), k = 1.9 (0.5-3.8); CLPS-IMRT 24.0 Gy (17.7-30.1), k = 2.1 (0.1-4.1). CONCLUSION: BSLPS-IMRT reduces the risk of developing high-grade subjective xerostomia compared with CLPS-IMRT. The D50 of the superficial lobe may be a more reliable predictor of recovery of parotid function than the whole gland mean dose. PMID- 26994896 TI - Growth impairment in children with pulmonary hypertension. PMID- 26994895 TI - The novel R347g pathogenic mutation of aromatic amino acid decarboxylase provides additional molecular insights into enzyme catalysis and deficiency. AB - We report here a clinical case of a patient with a novel mutation (Arg347->Gly) in the gene encoding aromatic amino acid decarboxylase (AADC) that is associated with AADC deficiency. The variant R347G in the purified recombinant form exhibits, similarly to the pathogenic mutation R347Q previously studied, a 475 fold drop of kcat compared to the wild-type enzyme. In attempting to unravel the reason(s) for this catalytic defect, we have carried out bioinformatics analyses of the crystal structure of AADC-carbidopa complex with the modelled catalytic loop (residues 328-339). Arg347 appears to interact with Phe103, as well as with both Leu333 and Asp345. We have then prepared and characterized the artificial F103L, R347K and D345A mutants. F103L, D345A and R347K exhibit about 13-, 97-, and 345-fold kcat decrease compared to the wild-type AADC, respectively. However, unlike F103L, the R347G, R347K and R347Q mutants as well as the D345A variant appear to be more defective in catalysis than in protein folding. Moreover, the latter mutants, unlike the wild-type protein and the F103L variant, share a peculiar binding mode of dopa methyl ester consisting of formation of a quinonoid intermediate. This finding strongly suggests that their catalytic defects are mainly due to a misplacement of the substrate at the active site. Taken together, our results highlight the importance of the Arg347-Leu333-Asp345 hydrogen-bonds network in the catalysis of AADC and reveal the molecular basis for the pathogenicity of the variants R347. Following the above results, a therapeutic treatment for patients bearing the mutation R347G is proposed. PMID- 26994897 TI - Growth in children with pulmonary arterial hypertension: a longitudinal retrospective multiregistry study. AB - BACKGROUND: To enable adequate interpretation of growth measurements in the management of children with pulmonary arterial hypertension (PAH), we assessed growth and its associated determinants in children with PAH. METHODS: We did a retrospective longitudinal study of height and body-mass index in reference to WHO growth standards by pooling data from four contemporary prospective registries of paediatric PAH representing 53 centres in 19 countries. The main outcome measures were median height for age and body-mass index for age percentiles and longitudinal deviation of height for age and body-mass index for age Z scores from WHO standards. FINDINGS: 601 children were followed up for a median of 2.9 years (IQR 1.5-4.4). Baseline median height for age percentile was 26 (IQR 4-54) and baseline median body-mass index for age percentile was 41 (IQR 12-79). Mean height for age Z score was significantly lower than the reference ( 0.81, 95% CI -0.93 to -0.69; p<0.0001), as was body-mass index for age Z score ( 0.12, -0.25 to -0.01; p=0.047). Height for age Z score was particularly decreased in young patients (aged <=5 years) with idiopathic or hereditary PAH and in all patients with PAH associated with congenital heart disease. Although Z scores increased in some patients and decreased in others, we detected no significant trend in height for age Z score (p=0.57) or body-mass index for age Z score (p=0.48) before taking account of covariates. Multivariable linear mixed effects modelling showed that age, cause of PAH, ex-prematurity, WHO functional class, trisomy 21, and time since diagnosis were associated with height for age Z score, whereas age, ethnicity, and trisomy 21 were associated with body-mass index for age Z score. A favourable WHO functional class course was independently associated with increases in height for age Z score. INTERPRETATION: PAH is associated with impaired growth, especially in younger children and those with pulmonary arterial hypertension associated with congenital heart disease. The degree of impairment is independently associated with cause of PAH and comorbidities, but also with disease severity and duration. Because a favourable clinical course was associated with catch-up growth, height for age could serve as an additional and globally available clinical parameter to monitor patients' clinical condition. FUNDING: Actelion Pharmaceuticals. PMID- 26994899 TI - Domestic violence and its associated factors among married women of a village development committee of rural Nepal. AB - BACKGROUND: Violence against women is a global public health problem occurring in multitude of contexts and domestic violence is considered to be the most pervasive one. Poor enforcement of policies, limitation of researches and expertise in this field largely accounts for persistence of this problem and nature of domestic violence and its associated factors are poorly understood. OBJECTIVES: This research aimed to estimate the magnitude of different forms of domestic violence and identify its associated factors. METHODS: Community based cross sectional study was conducted among 355 married women of reproductive age group of Kusheshwor, Sindhuli, Nepal. The questionnaire adapted from the World Health Organization Multi-Country Study was used for the face to face interviews. Occurrence of current domestic violence was used as outcome variable in logistic regression. Descriptive and multivariate analysis were performed in order to assess the magnitude of domestic violence and to identify its associated factors respectively. RESULTS: Self-reported lifetime prevalence of physical violence was 29.6% and past year prevalence was 15.2%, while corresponding figures for sexual violence were 6.8 and 2.3%, and for psychological violence were 31.0 and 18.3%. Lifetime domestic violence was 38.6% while in past 12 months, prevalence was 23.1%. Furthermore, 12.4% of women were experiencing all forms of violence concurrently. Women with controlling husband and having poor mental health were found to be at higher risk of domestic violence. CONCLUSIONS: Domestic violence is still rampant in our society with several forms of violence occurring together. In a country like Nepal, differentials power in relationship and poor mental health was found to be positively associated with violent episodes. This study highlights the infringement of women rights which can be the cause for serious public health consequences. PMID- 26994898 TI - Effects of Shock Waves on Expression of IL-6, IL-8, MCP-1, and TNF-alpha Expression by Human Periodontal Ligament Fibroblasts: An In Vitro Study. AB - BACKGROUND: Extracorporeal shock wave therapy (ESWT) can modulate cell behavior through mechanical information transduction. Human periodontal ligament fibroblasts (hPDLF) are sensible to mechanical stimulus and can express pro inflammatory molecules in response. The aim of this study was to evaluate the impacts of shock waves on interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor-alpha (TNF-alpha) expression by hPDLF. MATERIAL/METHODS: After being treated by shock waves with different parameters (100-500 times, 0.05-0.19 mJ/mm(2)), cell viability was tested using CCK-8. IL-6, IL-8, MCP-1, and TNF-alpha gene expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and IL-6 and IL-8 protein was measured by enzyme-linked immunosorbent assay (ELISA) at different time points. RESULTS: Shock waves with the parameters used in this study had no significant effects on the viability of hPDLF. A statistical inhibition of IL-6, IL-8, MCP-1, and TNF-alpha expression during the first few hours was observed (P<0.05). Expression of IL-8 was significantly elevated in the group receiving the most pulses of shock wave (500 times) after 4 h (P<0.05). At 8 h and 24 h, all treated groups demonstrated significantly enhanced IL-6 expression (P<0.05). TNF-alpha expression in the groups receiving more shock pulses (300, 500 times) or the highest energy shock treatment (0.19 mJ/mm(2)) was statistically decreased (P<0.05) at 24 h. CONCLUSIONS: Under the condition of this study, a shock wave with energy density no higher than 0.19 mJ/mm(2) and pulses no more than 500 times elicited no negative effects on cell viability of hPDLF. After a uniform initial inhibition impact on expression of inflammatory mediators, a shock wave could cause dose-related up-regulation of IL-6 and IL-8 and down-regulation of TNF-alpha. PMID- 26994900 TI - Feasibility of injectable thermoreversible gels for use in intramuscular injection of parathyroid autotransplantation. AB - Surgical transplantation of parathyroid tissue into the forearm muscle is one of the most commonly used surgical techniques. While simple, the procedure suffers from drawbacks. This study evaluated the feasibility of thermoreversible gel as an injectable carrier for parathyroid autotransplantation. Polyethyleneglycol polyalanine-co-phenylalanine (PEG-PAF) thermoreversible gel (sol form at 4 degrees C, gel form at 37 degrees C) were manufactured. Thirty-eight Sprague Dawley rats were divided into two groups (19 control, C group; 19 experimental, P group). The parathyroid glands of rats were excised. Parathyroid tissues were transplanted into the muscle pocket in sternocleidomastoid muscle in the C group. In the P group, the tissues were injected into the same muscle mixed with 0.3 ml thermoreversible gel. The serum levels of parathyroid hormone (PTH), ionized calcium, and phosphorous were measured before surgical procedure, on 7, 21, 56, and 70 days after surgery. Histology and immunohistochemistry were performed. Preoperative median PTH level of the C and the P group were 60.80 and 43.85 pg/ml, respectively (p = 0.641). Seventy days after surgery, median PTH level was 32.8 and 25.61 pg/ml, respectively. On day 70, the PTH level was restored by 54 % in the C group and 56 % in the P group compared to the preoperative value (p = 0.620). There were no significant intergroup differences in the ionized calcium/phosphorous level. Histology and immunohistochemistry revealed the successful transplantation of parathyroid tissues into the muscles in both groups. In conclusion, the PEG-PAF-based thermoreversible gel is a good candidate carrier material for intramuscular parathyroid autotransplantation. PMID- 26994901 TI - Structural and functional changes of cortical and subcortical structures following peripheral vestibular damage in humans. PMID- 26994902 TI - Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation. AB - Disseminated glioneuronal tumors of childhood are rare. We present a retrospective IRB-approved review of the clinical course and frequency of BRAF mutations in disseminated glioneuronal tumors at two institutions. Defining features of our cohort include diffuse leptomeningeal-spread, often with a discrete spinal cord nodule and oligodendroglioma-like histologic features. Patients were identified through a pathology database search of all cases with disseminated low-grade neoplasms with an oligodendroglioma-like component. De identified clinical information was collected by chart review and all imaging was reviewed. We retrieved the results of targeted genomic analyses for alterations in BRAF. Ten patients (aged 2-14 years) were identified from the Dana Farber/Boston Children's Hospital and the Royal Children's Hospital, Melbourne pathology databases. Nine patients received chemotherapy. Eight patients are alive, although three have had episodes of progressive disease. We identified genomic alterations affecting the MAPK pathway in six patients. One patient had a germline RAF1 mutation and a clinical diagnosis of cardio-facio-cutaneous syndrome. BRAF duplications were identified in four and BRAF V600E mutation was identified in one. These data support the presence of targetable genomic alterations in this disease. PMID- 26994904 TI - Gender-specific incidence of autoimmune diseases from national registers. AB - BACKGROUND: It is widely believed that autoimmune diseases affect predominantly in women, but the available evidence came from case control study with potential selection and recall bias. We aimed to examine the gender-specific incidence of autoimmune diseases by using national wide registers in Sweden. METHODS: Swedish Hospital Discharge Register and Outpatient Register were used to identify a set of autoimmune diseases between 1987 and 2010. Gender-specific incidence rate was standardized directly according to the Swedish age distribution in 2000. RESULTS: A total of 403,757 individuals were diagnosed with autoimmune diseases between 1987 and 2010 in Sweden. The overall incidence of 32 autoimmune disease was 60% higher in women than men. Female predominance was noted in 18 specific diseases, whereas the rest of them showed no difference or male predominance. The age of onset was different between men and women in 27 autoimmune diseases. CONCLUSIONS: Our study suggested that the classical view of female predominance of autoimmune diseases may be far from striking than previously believed. Further studies are needed to examine whether there is true difference between men and women. PMID- 26994903 TI - Blockade of CD47 ameliorates autoimmune inflammation in CNS by suppressing IL-1 triggered infiltration of pathogenic Th17 cells. AB - The migration of Th17 cells into central nervous system (CNS) tissue is the key pathogenic step in experimental autoimmune encephalomyelitis (EAE) model. However, the mechanism underlying the pathogenic Th17 cell migration remains elusive. Here we report that blockade of CD47 with CD47-Fc fusion protein is effective in preventing and curing EAE by impairing infiltration of Th17 cells into CNS. However, CD47 deficiency does not directly impair the migration of Th17 cells. Mechanistic studies showed that CD47 deficiency inhibited degradation of inducible nitric oxide synthase (iNOS) in proteasome of macrophages by Src activation and led to the increased nitric oxide (NO) production. Then NO suppressed inflammasome activation-induced IL-1beta production. This lower IL 1beta reduces the expression of IL-1R1 and migration-related chemokine receptors on CD47(-/-) Th17 cells, inhibiting the ability of Th17 cells to infiltrate into the CNS of CD47(-/-) mice and therefore suppressing EAE development. In vivo administration of exogenous IL-1beta indeed promoted the infiltration CD47(-/-) Th17 cells into CNS and antagonized the protective role of CD47 deficiency in EAE pathogenesis. Our results demonstrate a potential preventive and therapeutic application of CD47 blockade in controlling EAE development. PMID- 26994905 TI - Nanovesicle-targeted Kv1.3 knockdown in memory T cells suppresses CD40L expression and memory phenotype. AB - Ca(2+) signaling controls activation and effector functions of T lymphocytes. Ca(2+) levels also regulate NFAT activation and CD40 ligand (CD40L) expression in T cells. CD40L in activated memory T cells binds to its cognate receptor, CD40, on other cell types resulting in the production of antibodies and pro inflammatory mediators. The CD40L/CD40 interaction is implicated in the pathogenesis of autoimmune disorders and CD40L is widely recognized as a therapeutic target. Ca(2+) signaling in T cells is regulated by Kv1.3 channels. We have developed lipid nanoparticles that deliver Kv1.3 siRNAs (Kv1.3-NPs) selectively to CD45RO(+) memory T cells and reduce the activation-induced Ca(2+) influx. Herein we report that Kv1.3-NPs reduced NFAT activation and CD40L expression exclusively in CD45RO(+) T cells. Furthermore, Kv1.3-NPs suppressed cytokine release and induced a phenotype switch of T cells from predominantly memory to naive. These findings indicate that Kv1.3-NPs operate as targeted immune suppressive agents with promising therapeutic potentials. PMID- 26994906 TI - Acute hypoxia up-regulates HIF-1alpha and VEGF mRNA levels in Amazon hypoxia tolerant Oscar (Astronotus ocellatus). AB - Amazon fish maintain oxygen uptake through a variety of strategies considered evolutionary and adaptive responses to the low water oxygen saturation, commonly found in Amazon waters. Oscar (Astronotus ocellatus) is among the most hypoxia tolerant fish in Amazon, considering its intriguing anaerobic capacity and ability to depress oxidative metabolism. Previous studies in hypoxia-tolerant and non-tolerant fish have shown that hypoxia-inducible factor-1alpha (HIF-1alpha) gene expression is positively regulated during low oxygen exposure, affecting vascular endothelial growth factor (VEGF) transcription and fish development or tolerance in different manners. However, whether similar isoforms exists in tolerant Amazon fish and whether they are affected similarly to others physiological responses to improve hypoxia tolerance remain unknown. Here we evaluate the hepatic HIF-1alpha and VEGF mRNA levels after 3 h of acute hypoxia exposure (0.5 mgO2/l) and 3 h of post-hypoxia recovery. Additionally, hematological parameters and oxidative enzyme activities of citrate synthase (CS) and malate dehydrogenase (MDH) were analyzed in muscle and liver tissues. Overall, three sets of responses were detected: (1) as expected, hematocrit, hemoglobin concentration, red blood cells, and blood glucose increased, improving oxygen carrying capacity and glycolysis potential; (2) oxidative enzymes from liver decreased, corroborating the tendency to a widespread metabolic suppression; and (3) HIF-1alpha and VEGF increased mRNA levels in liver, revealing their role in the oxygen homeostasis through, respectively, activation of target genes and vascularization. This is the first study to investigate a hypoxia-related transcription factor in a representative Amazon hypoxia-tolerant fish and suggests that HIF-1alpha and VEGF mRNA regulation have an important role in enhancing hypoxia tolerance in extreme tolerant species. PMID- 26994908 TI - Rhodamine Based Turn-On Sensors for Ni(2+) and Cr(3+) in Organic Media: Detecting CN(-) via the Metal Displacement Approach. AB - Two novel sensors bearing rhodamine B and quinoline units have been synthesized. One of these, 1, allows sensitive and selective detection of Ni(2+) and Cr(3+) by forming non-fluorescent (1-Ni(2+)) and fluorescent (1-Cr(3+)) complexes respectively. Both metals trigger the formation of highly colored ring-open spirolactam. These form excellent probes for CN(-) which quenches the fluorescence of the 1-Cr(3+) complex by extracting the Cr(3+). Both Cr(3+) and Cu(2+) gave color changes with 2, but they are easily identified separately via the large fluorescence enhancement that occurs only with Cr(3+). PMID- 26994907 TI - Ontogeny changes and weaning effects in gene expression patterns of digestive enzymes and regulatory digestive factors in spotted rose snapper (Lutjanus guttatus) larvae. AB - The study of digestive physiology is an important issue in species that have been introduced in aquaculture like the spotted rose snapper (Lutjanus guttatus). The aims of this study were to describe the expression of digestive enzymes (trypsinogen, chymotrypsinogen, alpha-amylase, lipoprotein lipase, phospholipase A and pepsinogen) and their relation with orexigenic (neuropeptide Y, NPY) and anorexigenic (cholecystokinin, CCK) factors during the larval development and to evaluate the effect of weaning in their expression. The results showed that the transcripts of all the assayed digestive enzymes, with the exception of pepsinogen, and NPY and CCK were already present in L. guttatus from the hatching stage. The expression of all the enzymes was low during the yolk-sac stage (0-2 days after hatching, DAH), whereas after the onset of exogenous feeding at 2 DAH, their expression increased and fluctuated throughout larval development, which followed a similar pattern as in other marine fish species and reflected changes in different types of food items and the progressive maturation of the digestive system. On the other hand, weaning of L. guttatus larvae from live prey onto a microdiet between 25 and 35 DAH significantly affected the relative expression of most pancreatic digestive enzymes during the first weaning days, whereas chymotrypsinogen 2 and lipoprotein lipase remained stable during this period. At the end of co-feeding, larvae showed similar levels of gene expression regardless of the diet (live prey vs. microdiet), which indicated that larvae of L. guttatus were able to adapt their digestive capacities to the microdiet. In contrast, feeding L. guttatus larvae with live feed or microdiet did not affect the expression of CCK and NPY. The relevance of these findings with regard to current larval rearing procedures of L. guttatus is discussed. PMID- 26994910 TI - Erratum to: Pharmacokinetic evaluation of nanoparticle albumin-bound paclitaxel delivered via hepatic arterial infusion in patients with predominantly hepatic metastases. AB - In the original article, corresponding author's given name and family name are flipped. It should be "Siqing Fu" rather than "Fu Siqing". PMID- 26994909 TI - A phase II, open-label trial of bortezomib (VELCADE((r))) in combination with gemcitabine and cisplatin in patients with locally advanced or metastatic non small cell lung cancer. AB - BACKGROUND: Bortezomib is a selective reversible proteasome inhibitor with proapoptotic effects. Preclinical and phase I clinical data suggest activity of bortezomib in NSCLC, either as monotherapy or in combination with chemotherapeutic agents including gemcitabine and cisplatin. METHODS: Chemotherapy-naive patients with inoperable stage IIIB or IV NSCLC were administered bortezomib 1 mg/m(2) i.v. on days 1 and 8, and starting on day 21 (cycle 2), bortezomib (days 1 and 8) in combination with gemcitabine 1000 mg/m(2), (days 1 and 8), and cisplatin 70 mg/m(2) (day 1) in cycles of 21 days. Up to 8 cycles of combination therapy could be administered; single-agent bortezomib was continued until disease progression or unacceptable toxicity. RESULTS: Fifty-three patients [median age 66 years; 79.2 % male; 96.2 % stage IV; performance status (ECOG) 0/1 73.6/26.4 %; adenocarcinoma 45.3 %, squamous cell carcinoma 41.5 %] were enrolled. All patients were evaluable for toxicity and 43 for efficacy. Grade 3-4 hematologic toxicity consisted of neutropenia (22.6 %) and thrombocytopenia (17 %). Grade 2-4 non-hematologic adverse events were fever (9.4 %), fatigue (20.8 %), infection (18.9 %), and dyspnea (15.1 %). There was no >grade 2 neurotoxicity. Febrile neutropenia occurred in two (1.9 %) patients, and there were three possibly treatment-related deaths (5.4 %). In the intention-to treat population, the objective response rate was 17 % (95 % CI 6.9-27.1 %). No difference in response rate was observed for squamous versus other histology (18.2 vs. 16.1 %, p = 0.845). The median progression-free survival was 2.5 months, the median overall survival 10.6 months and the 1-year survival rate 38.1 %. CONCLUSION: The incorporation of bortezomib into the gemcitabine/cisplatin regimen, in the dose and schedule used in this study, could not improve the efficacy of the chemotherapy regimen and has not to be further investigated. PMID- 26994911 TI - Assessing the state of the art in biomedical relation extraction: overview of the BioCreative V chemical-disease relation (CDR) task. AB - Manually curating chemicals, diseases and their relationships is significantly important to biomedical research, but it is plagued by its high cost and the rapid growth of the biomedical literature. In recent years, there has been a growing interest in developing computational approaches for automatic chemical disease relation (CDR) extraction. Despite these attempts, the lack of a comprehensive benchmarking dataset has limited the comparison of different techniques in order to assess and advance the current state-of-the-art. To this end, we organized a challenge task through BioCreative V to automatically extract CDRs from the literature. We designed two challenge tasks: disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction. To assist system development and assessment, we created a large annotated text corpus that consisted of human annotations of chemicals, diseases and their interactions from 1500 PubMed articles. 34 teams worldwide participated in the CDR task: 16 (DNER) and 18 (CID). The best systems achieved an F-score of 86.46% for the DNER task--a result that approaches the human inter-annotator agreement (0.8875)--and an F-score of 57.03% for the CID task, the highest results ever reported for such tasks. When combining team results via machine learning, the ensemble system was able to further improve over the best team results by achieving 88.89% and 62.80% in F-score for the DNER and CID task, respectively. Additionally, another novel aspect of our evaluation is to test each participating system's ability to return real-time results: the average response time for each team's DNER and CID web service systems were 5.6 and 9.3 s, respectively. Most teams used hybrid systems for their submissions based on machining learning. Given the level of participation and results, we found our task to be successful in engaging the text-mining research community, producing a large annotated corpus and improving the results of automatic disease recognition and CDR extraction. Database URL: http://www.biocreative.org/tasks/biocreative v/track-3-cdr/. PMID- 26994912 TI - GO annotation in InterPro: why stability does not indicate accuracy in a sea of changing annotations. AB - The removal of annotation from biological databases is often perceived as an indicator of erroneous annotation. As a corollary, annotation stability is considered to be a measure of reliability. However, diverse data-driven events can affect the stability of annotations in both primary protein sequence databases and the protein family databases that are built upon the sequence databases and used to help annotate them. Here, we describe some of these events and their consequences for the InterPro database, and demonstrate that annotation removal or reassignment is not always linked to incorrect annotation by the curator. Database URL: http://www.ebi.ac.uk/interpro. PMID- 26994913 TI - Diagnosis of subclinical mastitis in Santa Ines and Morada Nova sheep in southeastern Brazil. AB - The objective of this study was to evaluate different screening limits for the California mastitis test (CMT) and the somatic cell count (SCC) in previous diagnoses of subclinical mastitis in Santa Ines and Morada Nova ewes, which were reared under the same management conditions. Additionally, cutoff points were defined for SCC in accordance with the sensitivity and specificity of the test. A total of 907 mammary halves were subjected to CMT and SCC. The disease was confirmed by means of microbiological identification. Coagulase-negative staphylococci (CNS) were the microorganisms with highest occurrence. The CMT score of 1+ provided adequate sensitivity and specificity at all periods of lactation investigated. This score showed good agreement with SCC, >400,000 cells mL(-1). Higher cell counts favored higher diagnostic specificity. They can be used when producers have financial difficulties relating to treatment or culling of sheep with subclinical mastitis. However, producers should be warned about the risk of false-negative results in the flock. PMID- 26994914 TI - Using the mini-VIDAS((r)) Easy Salmonella protocol to assess contamination in transitional and coastal waters. AB - Classical methodologies for Salmonella detection may be too long in time to assure public safety. Presently, one of the fastest assays for Salmonella detection using the mini-VIDAS((r)) system is the Easy Salmonella protocol. This assay, developed for food matrixes analysis, was here assessed for the applicability on the detection of these bacteria in transitional and saltwaters. The presence of Salmonella was detected in 4.2 % of the samples studied. In these transitional waters, the proposed protocol presented an efficiency of 79.1 %, due to a high false positive rate (20.8 %), and a false negative rate of 0 %-implying reducing analysis time, the use of enrichment broths, and making it more cost effective. Despite the multitude of samples nature, the method here described revealed to be an efficient and promising tool for transitional waters analysis. PMID- 26994915 TI - Apolipoprotein A-I and Paraoxonase-1 Are Potential Blood Biomarkers for Ischemic Stroke Diagnosis. AB - BACKGROUND: Blood biomarkers for ischemic and hemorrhagic stroke diagnosis remain elusive. Recent investigations suggested that apolipoprotein (Apo), matrix metalloproteinase (MMP), and paraoxonase-1 may be associated with stroke. We hypothesized that Apo A-I, Apo C-I, Apo C-III, MMP-3, MMP-9, and paraoxonase-1 are differentially expressed in ischemic stroke, hemorrhagic stroke, and controls. METHODS: In a single-center prospective observational study, consecutive stroke cases were enrolled if blood samples were obtainable within 12 hours of symptom onset. Age- (+/-5 years), race-, and sex-matched controls were recruited. Multiplex assays were used to measure protein levels. The Wilcoxon signed-rank test and the Mann-Whitney U-test were used to compare biomarker values between ischemic stroke patients and controls, hemorrhagic stroke patients and controls, and ischemic and hemorrhagic stroke patients. The 95% confidence intervals (CIs) for the difference of 2 medians were calculated. RESULTS: Fourteen ischemic stroke case-control pairs and 23 intracerebral hemorrhage (ICH) case-control pairs were enrolled. Median Apo A-I levels were lower in ischemic stroke cases versus controls (140 mg/dL versus 175 mg/dL, difference of 35 mg/dL, 95% CI -54 to -16) and in ischemic stroke versus ICH cases (140 mg/dL versus 180 mg/dL, difference of 40 mg/dL, 95% CI -57 to -23). Median paraoxonase-1 was lower in ischemic stroke cases than in both ICH cases and matched controls. Median Apo C-I was slightly lower in ischemic stroke cases than in ICH cases. There were no differences between groups for MMP-3, MMP-9, and Apo C-III. CONCLUSION: Apo A-I and paraoxonase-1 levels may be clinically useful for ischemic stroke diagnosis and for differentiating between ischemic and hemorrhagic strokes. PMID- 26994916 TI - Long-term prognostic outcome of cT1 gastric cancer patients who underwent laparoscopic gastrectomy after 5-year follow-up. AB - PURPOSE: We have reported that short-term and middle-term clinical outcomes including prognosis after laparoscopy-assisted gastrectomy (LAG) are excellent in cT1 gastric cancer. METHODS: In this study, long-term prognosis was finally confirmed in detail in 491 cT1 gastric cancer patients who underwent LAG between 1998 and 2010, where clinical course was completely pursued for recurrent cases. RESULTS: Among the 491 cases, follow-up examination at 5 years (60 months) after operation was done in 423 (86.2 %). Recurrent cases were seen in nine cases (1.8 %) who inevitably died despite aggressive multimodality treatments. The initial recurrent sites were the peritoneum in three, the liver in two, the bone in one, the ovary in one, the liver/bone in one, and the Virchow lymph node/bone in one. As a result, the 5-year disease-specific survival (DSS) was 98.3 %. cT1 gastric cancer was finally diagnosed as pathological stages IA to III, and the 5-year DSS was 99.7 % in pathological stage IA, 96.9 % in pathological stage IB, and 81 % in pathological stage II/III. The initial recurrent sites were the liver/bone in stage IA (M/N0), the liver in stage IB (MP/N0), the liver in stage IIA (MP/N1), the liver and the ovary in two stages IIB (T1N3), 3 peritoneum and 1 Virchow lymph node/bone in four stage III cases. Importantly, there were no initial recurrences in the regional lymph node, and all recurrences were seen within 5 years after operation. CONCLUSIONS: Although long-term prognostic outcome was extremely good in cT1 gastric cancer patients who underwent LAG, cases with recurrence inevitably died due to disease progression. PMID- 26994917 TI - German recommendations for pretransplantation donor kidney biopsies. AB - PURPOSE: This manuscript reviews the data about the histopathologic and develops recommendations to standardise and improve the biopsy procedure, the biopsy handling, the histopathological evaluation, the communication of results and the collection of data from pretransplantation kidney biopsies of deceased donors in Germany. METHODS: The recommendations are based on this literature review, on discussions at two workshops held by the German Society of Pathology and the German Organ Transplantation Foundation and on personal experiences of the authors. RESULTS: These German recommendations advocate the use of punch biopsies, paraffin embedding and detailed descriptive reporting of histopathological findings. CONCLUSIONS: These recommendations constitute only a starting point. Periodical revisions will help to simplify and optimise the recommendations with the ultimate goal to prospectively gather data for the elaboration of a computer-based algorithm that allows the exact prediction of transplantation outcome for a given match of donor and recipient. PMID- 26994918 TI - Effects of oxidative stress-induced changes in the actin cytoskeletal structure on myoblast damage under compressive stress: confocal-based cell-specific finite element analysis. AB - Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myoblasts and presented a finite element (FE) analysis of how such changes in the actin cytoskeletal structure affected a myoblast's capability to resist damage under compression. A confocal-based cell specific FE model was built to parametrically study the effects of stress fiber density, fiber cross-sectional area, fiber tensile prestrain, as well as the elastic moduli of the stress fibers, actin cortex, nucleus and cytoplasm. The results showed that a decrease in the elastic moduli of both the stress fibers and actin cortex could increase the average tensile strain on the actin cortex membrane structure and reduce the apparent cell elastic modulus. Assuming the cell would die when a certain percentage of membrane elements were strained beyond a threshold, a lower elastic modulus of actin cytoskeleton would compromise the compressive resistance of a myoblast and lead to cell death more readily. This model was used with a Weibull distribution function to successfully describe the extent of myoblasts damaged in a monolayer under compression. PMID- 26994919 TI - Wide tolerance to amino acids substitutions in the OCTN1 ergothioneine transporter. AB - BACKGROUND: Organic cation transporters transfer solutes with a positive charge across the plasma membrane. The novel organic cation transporter 1 (OCTN1) and 2 (OCTN2) transport ergothioneine and carnitine, respectively. Mutations in the SLC22A5 gene encoding OCTN2 cause primary carnitine deficiency, a recessive disorders resulting in low carnitine levels and defective fatty acid oxidation. Variations in the SLC22A4 gene encoding OCTN1 are associated with rheumatoid arthritis and Crohn disease. METHODS: Here we evaluate the functional properties of the OCTN1 transporter using chimeric transporters constructed by fusing different portion of the OCTN1 and OCTN2 cDNAs. Their relative abundance and subcellular distribution was evaluated through western blot analysis and confocal microscopy. RESULTS: Substitutions of the C-terminal portion of OCTN1 with the correspondent residues of OCTN2 generated chimeric OCTN transporters more active than wild-type OCTN1 in transporting ergothioneine. Additional single amino acid substitutions introduced in chimeric OCTN transporters further increased ergothioneine transport activity. Kinetic analysis indicated that increased transport activity was due to an increased V(max), with modest changes in K(m) toward ergothioneine. CONCLUSIONS: Our results indicate that the OCTN1 transporter is tolerant to extensive amino acid substitutions. This is in sharp contrast to the OCTN2 carnitine transporter that has been selected for high functional activity through evolution, with almost all substitutions reducing carnitine transport activity. GENERAL SIGNIFICANCE: The widespread tolerance of OCTN1 to amino acid substitutions suggests that the corresponding SLC22A4 gene may have derived from a recent duplication of the SLC22A5 gene and might not yet have a defined physiological role. PMID- 26994920 TI - Contribution of inorganic polyphosphate towards regulation of mitochondrial free calcium. AB - BACKGROUND: Calcium signaling plays a key role in the regulation of multiple processes in mammalian mitochondria, from cellular bioenergetics to the induction of stress-induced cell death. While the total concentration of calcium inside the mitochondria can increase by several orders of magnitude, the concentration of bioavailable free calcium in mitochondria is maintained within the micromolar range by the mitochondrial calcium buffering system. This calcium buffering system involves the participation of inorganic phosphate. However, the mechanisms of its function are not yet understood. Specifically, it is not clear how calcium orthophosphate interactions, which normally lead to formation of insoluble precipitates, are capable to dynamically regulate free calcium concentration. Here we test the hypothesis that inorganic polyphosphate, which is a polymerized form of orthophosphate, is capable to from soluble complexes with calcium, playing a significant role in the regulation of the mitochondrial free calcium concentration. METHODS: We used confocal fluorescence microscopy to measure the relative levels of mitochondrial free calcium in cultured hepatoma cells (HepG2) with variable levels of inorganic polyphosphate (polyP). RESULTS: The depletion of polyP leads to the significantly lower levels of mitochondrial free calcium concentration under conditions of pathological calcium overload. These results are coherent with previous observations showing that inorganic polyphosphate (polyP) can inhibit calcium-phosphate precipitation and, thus, increase the amount of free calcium. CONCLUSIONS: Inorganic polyphosphate plays an important role in the regulation of mitochondrial free calcium, leading to its significant increase. GENERAL SIGNIFICANCE: Inorganic polyphosphate is a previously unrecognized integral component of the mitochondrial calcium buffering system. PMID- 26994921 TI - Coupling between anammox and autotrophic denitrification for simultaneous removal of ammonium and sulfide by enriched marine sediments. AB - In the present study, the capacity of enrichments derived from marine sediments collected from different sites of the Mexican littoral to perform anaerobic ammonium oxidation (anammox) coupled to sulfide-dependent denitrification for simultaneous removal of ammonium and sulfide linked to nitrite reduction was evaluated. Sulfide-dependent denitrification out-competed anammox during the simultaneous oxidation of sulfide and ammonium. Significant accumulation of elemental sulfur (ca. 14-30 % of added sulfide) occurred during the coupling between the two respiratory processes, while ammonium was partly oxidized (31-47 %) due to nitrite limitation imposed in sediment incubations. Nevertheless, mass balances revealed up to 38 % more oxidation of the electron donors available (ammonium and sulfide) than that expected from stoichiometry. Recycling of nitrite, from nitrate produced through anammox, is proposed to contribute to extra oxidation of sulfide, while additional ammonium oxidation is suggested by sulfate-reducing anammox (SR-anammox). The complex interaction between nitrogenous and sulfurous compounds occurring through the concomitant presence of autotrophic denitrification, conventional anammox and SR-anammox may significantly drive the nitrogen and sulfur fluxes in marine environments. PMID- 26994922 TI - Molecularly imprinted polymer-coated hollow fiber membrane for the microextraction of triazines directly from environmental waters. AB - In this work, novel molecularly imprinted polymer-coated hollow fibers (MIP-HFs) have been prepared and evaluated for the development of a micro-solid phase extraction method for the analysis of triazines in aqueous samples using high performance liquid chromatography and UV detection. The proposed extraction method combines liquid-liquid microextraction and molecular imprinting technology. In brief, a thin film of toluene is immobilised in the pores of the obtained MIP-HF. Afterwards, the conditioned MIP-HF is immersed in the water sample. Under stirring for a certain time, the target analytes are liquid-liquid extracted from the sample to the immobilised toluene and then these diffuse to the specific binding sites of the MIP. The effect of various experimental parameters as time and stirring-rate and salting-out effect among others, were studied for the establishment of optimum rebinding conditions. Recoveries for seven triazines tested in 100mL pure water samples spiked with 15 MUg L(-1) of each triazine were within 0.8-6.9%, with a relative standard deviation (RSD)<10% (n=3). The detection limits (LODs) were within 0.05-0.1 MUg L(-1), depending upon the triazine. The proposed methodology was successfully applied to extract the triazines from spiked tap and river water samples at MUg L(-1) concentration level. The mircroextraction procedure with the developed MIP-HFs overcomes the typical low performance and lack of selective recognition of MIPs in aqueous media, allowing the determination of triazines in environmental waters at expected real concentration levels. PMID- 26994923 TI - Comprehensive two-dimensional liquid chromatographic analysis of poloxamers. AB - Poloxamers are low molar mass triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), having number of applications as non-ionic surfactants. Comprehensive one and two-dimensional liquid chromatographic (LC) analysis of these materials is proposed in this study. The separation of oligomers of both types (PEO and PPO) is demonstrated for several commercial poloxamers. This is accomplished at the critical conditions for one of the block while interaction for the other block. Reversed phase LC at CAP of PEO allowed for oligomeric separation of triblock copolymers with regard to PPO block whereas normal phase LC at CAP of PPO renders oligomeric separation with respect to PEO block. The oligomeric separation with regard to PEO and PPO are coupled online (comprehensive 2D-LC) to reveal two-dimensional contour plots by unconventional 2D IC*IC (interaction chromatography) coupling. The study provides chemical composition mapping of both PEO and PPO, equivalent to combined molar mass and chemical composition mapping for several commercial poloxamers. PMID- 26994924 TI - Tailored sensitivity reduction improves pattern recognition and information recovery with a higher tolerance to varied sample concentration for targeted urinary metabolomics. AB - Variation in total metabolite concentration among different samples has been a major challenge for urinary metabolomics. Here we investigated the potential of tailored sensitivity reduction of high abundance metabolites for improved targeted urinary metabolomics. Two levels of sensitivity reduction of the 21 predominant urinary metabolites were assessed by employing less sensitive transition or collision energy with level 1 (reduced 1) and 2 (reduced 2) exhibiting 30-90% and 2-20% of the optimal sensitivity, respectively. Five postacquisition normalization methods were compared including no normalization, probabilistic quotient normalization, and normalization to sample median, creatinine intensity, and total intensity. Normalization to total intensity with reduced 2 gave the best pattern recognition and information recovery with a higher tolerance to varied sample concentration. Pareto scaling could improve the performance of tailored sensitivity reduction (reduced 2) for targeted urinary metabolomics while data transformation and autoscaling were susceptible to varied sample concentration. Using controlled spike-in experiments, we demonstrated that tailored sensitivity reduction revealed more differentially expressed markers with higher accuracy than did the conventional optimal sensitivity. This was particularly true when the differences between the sample groups are small. This work also served as an introductory guideline for handling targeted metabolomics data using the open-source software MetaboAnalyst. PMID- 26994925 TI - Incidence and risk factors for proximal junctional kyphosis: a meta-analysis. AB - PURPOSE: To analyse the incidence and risk factors associated with proximal junctional kyphosis (PJK) following spinal fusion, we collect relative statistics from the articles on PJK and perform a meta-analysis. METHODS: An extensive search of literature was performed in PubMed, Embase, and The Cochrane Library (up to April 2015). The following risk factors were extracted: age at surgery, gender, combined anterior-posterior surgery, use of pedicle screw at top of construct, hybrid instrumentation, thoracoplasty, fusion to sacrum (S1), preoperative thoracic kyphosis angle (T5-T12) >40 degrees , bone mineral density (BMD) and preoperative to postoperative sagittal vertical axis (SVA difference) >5 cm. Data analysis was conducted with RevMan 5.3 and STATA 12.0. RESULTS: A total of 14 unique studies including 2215 patients were included in the final analyses. The pooled analysis showed that there were significant difference in age at surgery >55 years old (OR 2.19, 95 % CI 1.36-3.53, p = 0.001), fusion to S1 (OR 2.12, 95 % CI 1.57-2.87, p < 0.001), T5-T12 >40 degrees (OR 2.68, 95 % CI 1.73-4.13, p < 0.001), low BMD (OR 2.37, 95 % CI 1.45-3.87, p < 0.001) and SVA difference >5 cm (OR 2.53, 95 % CI 1.24-5.18, p = 0.01). However, there was no significant difference in gender (OR 0.98, 95 % CI 0.74-1.30, p = 0.87), combined anterior-posterior surgery (OR 1.55, 95 % CI 0.98-2.46, p = 0.06), use of pedicle screw at top of construct (OR 1.55, 95 % CI 0.67-3.59, p = 0.30), hybrid instrumentation (OR 1.31, 95 % CI 0.92-1.87, p = 0.13) and thoracoplasty (OR 1.55, 95 % CI 0.89-2.72, p = 0.13). The incidence of PJK following spinal fusion was 30 % (ranged from 17 to 62 %) based on the 14 studies. CONCLUSIONS: The results of our meta-analysis suggest that age at surgery >55 years, fusion to S1, T5-T12 >40 degrees , low BMD and SVA difference >5 cm are risk factors for PJK. However, gender, combined anterior-posterior surgery, use of pedicle screw at top of construct, hybrid instrumentation and thoracoplasty are not associated with PJK. PMID- 26994927 TI - The complete mitochondrial genome of the black surfperch, Embiotoca jacksoni: Selection and substitution rates among surfperches (Embiotocidae). AB - The complete 16,515bp nucleotide sequence of the mitochondrial genome was determined for the black surfperch, Embiotoca jacksoni (Perciformes: Embiotocidae). The black surfperch mitochondrial genome contains 13 protein coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and the non-coding control region (D-loop), the gene order of which is identical to that observed in most vertebrates. The protein-coding gene sequences of E. jacksoni mitochondrial DNA were compared with two other embiotocid surfperches with available complete mitochondrial genomes, Cymatogaster aggregata and Ditrema temminckii. Across all mitochondrial protein-coding genes in surfperches the weighted average substitution rate was 2.079% per My and average dN/dS ratios for each protein coding gene ranged from 0.016 in CytB to 0.608 in ND3. Substitution rates and dN/dS ratios were relatively high for ATP8 compared to other protein-coding genes. Although most protein-coding genes showed signals of purifying selection, we found evidence for positive selection in ND3 in E. jacksoni. PMID- 26994926 TI - Prevalence of axial symptoms after posterior cervical decompression: a meta analysis. AB - PURPOSE: To investigate the prevalence of axial symptoms (AS) in patients following posterior cervical decompression. METHODS: We searched the PubMed, Embase, and Cochrane databases for relevant studies that reported the incidence of AS after posterior cervical decompression, and manually screened reference lists for additional studies. Relevant prevalence estimates were calculated. Subgroup analysis, sensitivity analysis and publication bias assessment were also performed. RESULTS: Our meta-analysis included 44 studies, with 893 AS cases in 2984 patients. The pooled AS prevalence was 28 % (95 % CI 24-32). The prevalence of AS was higher after expansive open-door laminoplasty (39 %) than after modified open-door laminoplasty (MOLP, 23 %) and laminectomy instrumented fusion (29 %). AS prevalence was also higher in those that wore a neck collar for 2-3 months (34 %) compared with 2 weeks (21 %). The lowest AS prevalence (9 %) was found in patients who underwent MOLP with C3 laminectomy and C7 spinous processes conserved. There was an intermediate AS prevalence after MOLP with C7 spinous processes conserved (16 %), MOLP with preservation of the unilateral posterior muscular-ligament complex (19 %), MOLP with C3 laminectomy (22 %), and MOLP with plate fixation (23 %). Prevalence of AS might be higher in patients <60 years and increased in populations with a higher proportion of females. CONCLUSIONS: Posterior cervical surgery carries a high risk of postoperative AS. Postoperative AS may be reduced through preserving posterior muscles and structures, stabilizing cervical vertebrae, and reducing external cervical immobilization time. PMID- 26994928 TI - Dietary nitrate and nitrite: Benefits, risks, and evolving perceptions. AB - Consumers have an illogical relationship with nitrite (and its precursor, nitrate) in food. Despite a long history of use, nitrite was nearly banned from use in foods in the 1970s due to health concerns related to the potential for carcinogenic nitrosamine formation. Changes in meat processing methods reduced those potential risks, and nitrite continued to be used in foods. Since then, two opposing movements continue to shape how consumers view dietary nitrate and nitrite. The discovery of the profound physiological importance of nitric oxide led to the realization that dietary nitrate contributes significantly to the nitrogen reservoir for nitric oxide formation. Numerous clinical studies have also demonstrated beneficial effects from dietary nitrate consumption, especially in vascular and metabolic health. However, the latest wave of consumer sentiment against food additives, the clean-label movement, has renewed consumer fear and avoidance of preservatives, including nitrite. Education is necessary but may not be sufficient to resolve this disconnect in consumer perception. PMID- 26994929 TI - A case of schwannoma of the mesoesophagus displaced from the left to the right of the posterior mediastinum. AB - Although schwannomas are the most common neurogenic tumors found in the thorax, schwannomas of the mesoesophagus are extremely rare. We report a case of an 80 year-old man having a tumor in contact with the esophagus in the left posterior mediastinum. A preoperative follow-up computed tomography scan showed tumor displacement from the left to the right of the posterior mediastinum. The patient underwent surgery, and the tumor was diagnosed as a schwannoma of the mesoesophagus. The tumor might have been displaced from the left to the right of the posterior mediastinum because it was located in the mesoesophagus. PMID- 26994932 TI - Spatial distribution and activity of Na(+)/K(+)-ATPase in lipid bilayer membranes with phase boundaries. AB - We have reconstituted functional Na(+)/K(+)-ATPase (NKA) into giant unilamellar vesicles (GUVs) of well-defined binary and ternary lipid composition including cholesterol. The activity of the membrane system can be turned on and off by ATP. The hydrolytic activity of NKA is found to depend on membrane phase, and the water relaxation in the membrane on the presence of NKA. By collapsing and fixating the GUVs onto a solid support and using high-resolution atomic-force microscopy (AFM) imaging we determine the protein orientation and spatial distribution at the single-molecule level and find that NKA is preferentially located at lo/ld interfaces in two-phase GUVs and homogeneously distributed in single-phase GUVs. When turned active, the membrane is found to unbind from the support suggesting that the protein function leads to softening of the membrane. PMID- 26994930 TI - Pulmonary hypertension in thyroid diseases. AB - The influence of thyroid hormones on cardiovascular system is well established. Thyroid diseases can effectively enhance the alteration on cardiovascular system by influencing chronotropic and inotropic actions of the heart; altering the strength and the speed of contraction, the speed of relaxation, the duration of the potential of action, and the duration of the refractory period and atrio ventricular conduction time; modulating circulation and peripheral vascular beds. One of the more intriguing insights in the connection between thyroid diseases and cardiovascular alterations is related to the evaluation of the influence of thyroid hormones on pulmonary vascular beds. Literature reported several studies regarding the association between both hypothyroidism and hyperthyroidism and the occurrence of increased vascular pulmonary arterial pressure. Nevertheless, the pathogenetic mechanisms able to explain such relationship are not fully understood. Many doubts still persist in the comprehension of the mechanisms of pulmonary hypertension in thyroid diseases. The aim of this review was to provide possible explanation about the possible interaction between pulmonary vascular beds and thyroid function in order to evaluate the possibility of novel perspectives in the general management of patients suffering from thyroid and cardiovascular diseases. PMID- 26994933 TI - Analysis of the factors linked to a diagnosis of attention deficit hyperactivity disorder in children. AB - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder originating from multiple factors. The aim of this study is to determine the percentage of patients with ADHD out of all patients referred to our clinic for assessment, and to explore the epidemiological and clinical factors linked to this diagnosis. PATIENTS AND METHODS: retrospective analytical study of a sample of patients under 15 years old sent to the paediatric neurology clinic for suspected ADHD. DSM-IV criteria were used for diagnosis. We completed a binary logistic regression analysis to determine which risk factors were associated with the diagnosis. RESULTS: Of the 280 selected patients, 224 were male (male/female ratio 4:1); mean age (SD) was 8.4 (3.08) years. Almost half (49%) of the patients were referred by their schools and 64.9% were born in the second half of the year, but this tendency was more marked in girls than in boys. Assessment according to DSM-IV criteria resulted in diagnosis of 139 subjects (49.7%). The risk factors linked to diagnosis were male sex, parents with ADHD, associated sleep disorders, tics, and absence of neurodevelopmental delay. CONCLUSION: Only half of the children referred for suspected ADHD were diagnosed with that condition, and most were among the youngest in their classes, which suggests that suspected ADHD is overestimated. An exhaustive clinical interview investigating the family's psychological disorders and the patient's sleep disorders and tics is needed to improve the diagnostic process. PMID- 26994931 TI - Osteocalcin improves nonalcoholic fatty liver disease in mice through activation of Nrf2 and inhibition of JNK. AB - Recent studies have demonstrated a protective effect of osteocalcin against nonalcoholic fatty liver disease (NAFLD), although the specific underlying mechanisms remain unclear. Nrf2 and JNK pathways play important roles in the pathogenesis of NAFLD. The present study aimed to investigate whether osteocalcin protects against NAFLD by regulating these pathways. Male C57/BL6J mice were fed a high-fat diet for 12 weeks to induce NAFLD and were treated with recombinant decarboxylate osteocalcin (30 ng/g) or vehicle by daily intraperitoneal injection during this period. Osteocalcin treatment protected mice from diet-induced hepatic triglyceride accumulation and liver injury. Increased levels of malondialdehyde and 8-iso-prostaglandin F2alpha as well as a higher ratio of oxidized to reduced glutathione in the liver of mice fed a high-fat diet were significantly decreased due to the intervention of osteocalcin. Osteocalcin treatment not only activated Nrf2 nuclear translocation and up-regulated the expression of antioxidant enzyme genes (catalase, SOD, and GPx), but also inhibited the activation of JNK in the liver. GPRC6A, the putative receptor of osteocalcin, was found in the liver. In conclusion, these results suggest that osteocalcin improves NAFLD by activating the Nrf2 pathway to alleviate oxidative stress and inhibiting JNK pathway. PMID- 26994934 TI - What is a virus species? Radical pluralism in viral taxonomy. AB - Early attempts in the 1960s at constructing a classification scheme for viruses were phenetic and focused on structural properties of the virion. Over time, the International Committee on the Taxonomy of Viruses (ICTV) has refined its definition of a virus species to include an appeal to evolutionary history. The current ICTV definition defines a viral species in terms of monophyly. The existence of prolific horizontal genetic transfer (HGT) among various groups of viruses presents a challenge to this definition. I argue that the proper response to this mode of evolution is to allow for radical pluralism. Some viruses can be members of more than one species; others don't form species at all and should be classified using new reticulate categories. PMID- 26994935 TI - Viruses as living processes. AB - The view that life is composed of distinct entities with well-defined boundaries has been undermined in recent years by the realisation of the near omnipresence of symbiosis. What had seemed to be intrinsically stable entities have turned out to be systems stabilised only by the interactions between a complex set of underlying processes (Dupre, 2012). This has not only presented severe problems for our traditional understanding of biological individuality but has also led some to claim that we need to switch to a process ontology to be able adequately to understand biological systems. A large group of biological entities, however, has been excluded from these discussions, namely viruses. Viruses are usually portrayed as stable and distinct individuals that do not fit the more integrated and collaborative picture of nature implied by symbiosis. In this paper we will contest this view. We will first discuss recent findings in virology that show that viruses can be 'nice' and collaborate with their hosts, meaning that they form part of integrated biological systems and processes. We further offer various reasons why viruses should be seen as processes rather than things, or substances. Based on these two claims we will argue that, far from serving as a counterexample to it, viruses actually enable a deeper understanding of the fundamentally interconnected and collaborative nature of nature. We conclude with some reflections on the debate as to whether viruses should be seen as living, and argue that there are good reasons for an affirmative answer to this question. PMID- 26994936 TI - Synthesis and characterization of brain penetrant prodrug of neuroprotective D 264: Potential therapeutic application in the treatment of Parkinson's disease. AB - Parkinson's disease (PD) is one of the major debilitating neurodegenerative disorders affecting millions of people worldwide. Progressive loss of dopamine neurons resulting in development of motor dysfunction and other related non-motor symptoms is the hallmark of PD. Previously, we have reported on the neuroprotective property of a potent D3 preferring agonist D-264. In our goal to increase the bioavailability of D-264 in the brain, we have synthesized a modified cysteine based prodrug of D-264 and evaluated its potential in crossing the blood-brain barrier. Herein, we report the synthesis of a novel modified cysteine conjugated prodrug of potent neuroprotective D3 preferring agonist D-264 and systematic evaluation of the hydrolysis pattern of the prodrug to yield D-264 at different time intervals in rat plasma and brain homogenates using HPLC analysis. Furthermore, we have also performed in vivo experiments with the prodrug to evaluate its enhanced brain penetration ability. PMID- 26994937 TI - Relationship between thigh intermuscular adipose tissue accumulation and number of metabolic syndrome risk factors in middle-aged and older Japanese adults. AB - BACKGROUND: To evaluate the association between thigh intermuscular adipose tissue accumulation and number of metabolic syndrome risk factors in middle-aged and older Japanese adults. METHODS: Thigh muscle cross-sectional area, subcutaneous adipose tissue, thigh intermuscular adipose tissue, abdominal subcutaneous adipose tissue, and visceral adipose tissue were measured in 166 middle-aged and older (mean age, 69years) Japanese adults using magnetic resonance imaging. Daily physical activity was calculated using pedometers, and energy intake per day was evaluated using 3-day dietary records. Multiple linear regression analysis was used to assess the association between intermuscular adipose tissue and the number of metabolic syndrome risk factors. RESULTS: Multiple regression analysis indicated that intermuscular adipose tissue was significantly associated with the number of metabolic syndrome risk factors, after adjusting for age, sex, body mass index, daily physical activity, energy intake, thigh muscle cross-sectional area, and visceral adipose tissue (p<0.05). CONCLUSIONS: Thigh intermuscular adipose tissue accumulation was significantly associated with the number of metabolic syndrome risk factors in middle-aged and older Japanese adults, independent of age, sex, body mass index, daily physical activity, energy intake, thigh muscle cross-sectional area, and visceral adipose tissue. PMID- 26994939 TI - Post-exposure vaccination with the vaccine candidate Bacillus Calmette-Guerin DeltaureC::hly induces superior protection in a mouse model of subclinical tuberculosis. AB - The tuberculosis vaccine BCG DeltaureC::hly is the most advanced BCG replacement candidate in phase II clinical development. Here we assess the protective capacity of the construct administered to mice as homologous prime-boost vaccine prior Mycobacterium tuberculosis infection and as post-exposure vaccine. Multiple immunization did not improve the superior protection of BCG DeltaureC::hly over BCG. Animals with subclinical tuberculosis were better protected when vaccinated with BCG DeltaureC::hly as compared to BCG. Our findings suggest further consideration of BCG DeltaureC::hly as post-exposure vaccine. PMID- 26994938 TI - Calorie restriction in overweight older adults: Do benefits exceed potential risks? AB - The evidence regarding recommendations of calorie restriction as part of a comprehensive lifestyle intervention to promote weight loss in obese older adults has remained equivocal for more than a decade. The older adult population is the fastest growing segment of the US population and a greater proportion of them are entering old age obese. These older adults require treatments based on solid evidence. Therefore the purpose of this review is three-fold: 1) to provide a more current status of the knowledge regarding recommendations of calorie restriction as part of a comprehensive lifestyle intervention to promote weight loss in obese older adults, 2) to determine what benefits and/or risks calorie restriction adds to exercise interventions in obese older adults, and 3) to consider not only outcomes related to changes in body composition, bone health, cardiometabolic disease risk, markers of inflammation, and physical function, but, also patient-centered outcomes that evaluate changes in cognitive status, quality of life, out-of-pocket costs, and mortality. Seven randomized controlled trials were identified that examined calorie restriction while controlling for exercise intervention effects. Overall, the studies found that calorie restriction combined with exercise is effective for weight loss. Evidence was mixed regarding other outcomes. The risk-benefit ratio regarding calorie restriction in older adults remains uncertain. Greater long-term follow-up is necessary, and complementary effectiveness studies are needed to identify strategies currently used by obese older adults in community settings. PMID- 26994941 TI - Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles. AB - 7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT 11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38 conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38 conjugate micelles. PMID- 26994940 TI - Is transesophageal echocardiogram mandatory in patients undergoing ablation of atrial fibrillation with uninterrupted novel oral anticoagulants? Results from a prospective multicenter registry. AB - BACKGROUND: Transesophageal echocardiography (TEE) is recommended in patients undergoing atrial fibrillation (AF) ablation, but use of this strategy is variable. OBJECTIVE: To evaluate whether TEE is necessary before AF ablation in patients treated with novel oral anticoagulants (NOACs). METHODS: We performed a prospective multicenter registry of AF patients undergoing radiofrequency catheter ablation on uninterrupted NOACs (apixaban and rivaroxaban). All patients were on NOACs for at least 4 weeks before ablation. Heparin bolus was administered to all patients before transseptal catheterization to maintain a target activated clotting time above 300 seconds. A subset of 86 patients underwent brain diffuse magnetic resonance imaging (dMRI) to detect silent cerebral ischemia (SCI). RESULTS: A total of 970 patients (514 [53%] apixaban patients and 456 [47%] rivaroxaban patients) were enrolled for this study. The mean age was 69.5 +/- 9.0 years, with 824 patients (85%) having nonparoxysmal AF, and 636 patients (65.6%) were male. The average CHA2DS2-VASc score was 3.01 +/- 1.3 and CHADS2 score was >=2 in 609 patients (62.8%). Intracardiac echocardiogram ruled out left atrial appendage thrombus in all patients whose left atrial appendage was visualized (692, 71%), and detected "smoke" in 407 patients (42%). SCI at postprocedure dMRI was detected in 2.3% (2/86). One thromboembolic event (transient ischemic attack) (0.10%) with positive dMRI occurred in a patient on uninterrupted rivaroxaban with longstanding persistent AF. CONCLUSION: Our study illustrates that performing AF ablation while on uninterrupted apixaban and rivaroxaban without TEE is feasible and safe. This finding has important clinical and economic relevance. PMID- 26994942 TI - Editorial overview: Macromolecular machines and assemblies. PMID- 26994943 TI - Population genetic structure and long-distance dispersal of a recently expanding migratory bird. AB - Long-distance dispersal events and their derivable increases of genetic diversity have been highlighted as important ecological and evolutionary determinants that improve performances of range-expanding species. In the context of global environmental change, specific dispersal strategies have to be understood and foreseen if we like to prevent general biodiversity impoverishment or the spread of allochthonous diseases. We explored the genetic structure and potential population mixing on the recently range-expanding European bee-eater Merops apiaster. In addition, the species is suspected of harbouring and disseminating the most relevant disease for bees and apiculture, Nosema microsporidia. In agreement with complementary ringing recovery data and morphometric measurements, genetic results on two mitochondrial genes and 12 microsatellites showed a reasonably well-structured population partitioning along its breeding distribution. Microsatellite results indicated that not only did a few birds recently disperse long distance during their return migrations and change their natal breeding areas, but also that a group of allochthonous birds together founded a new colony. Although we did not provide evidence on the direct implication of birds in the widespread of Nosema parasites, our finding on the long-distance dispersal of bird flocks between remote breeding colonies adds concern about the role of European bee-eaters in the spread of such disease at a large, inter-continental scale. PMID- 26994945 TI - beta-Amyloid precursor protein-b is essential for Mauthner cell development in the zebrafish in a Notch-dependent manner. AB - Amyloid precursor protein (APP) is a transmembrane glycoprotein that has been the subject of intense research because of its implication in Alzheimer's disease. However, the physiological function of APP in the development and maintenance of the central nervous system remains largely unknown. We have previously shown that the APP homologue in zebrafish (Danio rerio), Appb, is required for motor neuron patterning and formation. Here we study the function of Appb during neurogenesis in the zebrafish hindbrain. Partial knockdown of Appb using antisense morpholino oligonucleotides blocked the formation of the Mauthner neurons, uni- or bilaterally, with an aberrant behavior as a consequence of this cellular change. The Appb morphants had decreased neurogenesis, increased notch signaling and notch1a expression at the expense of deltaA/D expression. The Mauthner cell development could be restored either by a general decrease in Notch signaling through gamma-secretase inhibition or by a partial knock down of Notch1a. Together, this demonstrates the importance of Appb in neurogenesis and for the first time shows the essential requirement of Appb in the formation of a specific cell type, the Mauthner cell, in the hindbrain during development. Our results suggest that Appb-regulated neurogenesis is mediated through balancing the Notch1a signaling pathway and provide new insights into the development of the Mauthner cell. PMID- 26994944 TI - As above, so below: Auxin's role in lateral organ development. AB - Organogenesis requires the coordination of many highly-regulated developmental processes, including cell fate determination, cell division and growth, and cell cell communication. For tissue- and organ-scale coordination, a network of regulators enables molecular events in individual cells to translate into multicellular changes in structure and functional capacity. One recurrent theme in plant developmental networks is a central role for plant hormones, especially auxin. Here, we focus first on describing recent advances in understanding lateral root development, one of the best-studied examples of auxin-mediated organogenesis. We then use this framework to examine the parallel process of emergence of lateral organs in the shoot-a process called phyllotaxy. This comparison reveals a high degree of conservation, highlighting auxin's pivotal role determining overall plant architecture. PMID- 26994946 TI - Gia/Mthl5 is an aorta specific GPCR required for Drosophila heart tube morphology and normal pericardial cell positioning. AB - G-protein signaling is known to be required for cell-cell contacts during the development of the Drosophila dorsal vessel. However, the identity of the G protein-coupled receptor (GPCR) that regulates this signaling pathway activity is unknown. Here we describe the identification of a novel cardiac specific GPCR, called Gia, for "GPCR in aorta". Gia is the only heart-specific GPCR identified in Drosophila to date and it is specifically expressed in cardioblasts that fuse at the dorsal midline to become the aorta. Gia is the only Drosophila gene so far identified for which expression is entirely restricted to cells of the aorta. Deletion of Gia led to a broken-hearted phenotype, characterized by pericardial cells dissociated from cardioblasts and abnormal distribution of cell junction proteins. Both phenotypes were similar to those observed in mutants of the heterotrimeric cardiac G proteins. Lack of Gia also led to defects in the alignment and fusion of cardioblasts in the aorta. Gia forms a protein complex with G-alphao47A, the alpha subunit of the heterotrimeric cardiac G proteins and interacts genetically with G-alphao47A during cardiac morphogenesis. Our study identified Gia as an essential aorta-specific GPCR that functions upstream of cardiac heterotrimeric G proteins and is required for morphological integrity of the aorta during heart tube formation. These studies lead to a redefinition of the bro phenotype, to encompass morphological integrity of the heart tube as well as cardioblast-pericardial cell spatial interactions. PMID- 26994947 TI - The impact of concomitant procedures during endovascular abdominal aortic aneurysm repair on perioperative outcomes. AB - BACKGROUND: Concomitant procedures during endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm are performed to facilitate endograft delivery, to simultaneously treat unrelated conditions, or to resolve intraoperative pitfalls. The frequency and perioperative impact of these procedures are not well described. This study aimed to assess the frequency and perioperative impact of various concomitant procedures performed at the time of EVAR. METHODS: We included all elective EVARs in the Vascular Study Group of New England between January 2003 and November 2014 and identified those with and those without concomitant procedures. Multivariable logistic regression analysis was used to establish the independent association between concomitant procedures and perioperative outcomes. RESULTS: The study included 4033 patients, with 1168 (29.0%) patients undergoing one or more additional procedures. Independent risk factors for 30-day mortality were concomitant femoral endarterectomy (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.1-11.2) and renal angioplasty or stenting (OR, 3.1; 95% CI, 1.2-8.3). Postoperative bowel ischemia was associated with hypogastric embolization (OR, 3.8; 95% CI, 1.1-13.4) and iliac angioplasty or stenting (OR, 3.5; 95% CI, 1.3-9.6). Leg ischemia was associated with unplanned graft extension (OR, 2.3; 95% CI, 1.02-5.0), other artery reconstruction (OR, 5.2; 95% CI, 1.8-15.1), thromboembolectomy (OR, 5.2; 95% CI, 1.3-20.8), and repair of arterial injury (OR, 4.6; 95% CI, 1.2-18.3). Risk factors for deterioration of renal function were iliofemoral bypass (OR, 3.9; 95% CI, 1.3-12.2), other artery reconstruction (OR, 2.7; 95% CI, 1.3-5.8), renal angioplasty or stenting (OR, 2.5; 95% CI, 1.3-4.6), and repair of arterial injury (OR, 4.5; 95% CI, 1.6-12.2). Myocardial infarction was associated with femorofemoral bypass (OR, 3.9; 95% CI, 1.7-8.7), other artery reconstruction (OR, 3.9; 95% CI, 1.6-9.2), and repair of arterial injury (OR, 6.1; 95% CI, 1.8-21.0). Wound complications were predicted by femorofemoral bypass (OR, 13.4; 95% CI, 5.8 31.1). CONCLUSIONS: Concomitant procedures during EVAR are associated with increased postoperative morbidity and mortality. The need for performing concomitant procedures should be carefully considered. The morbidity associated with intraoperative complications highlights the importance of avoidance of arterial injury and thromboembolic events where possible. PMID- 26994948 TI - Results after elective open repair of pararenal abdominal aortic aneurysms. AB - OBJECTIVE: This study presents a retrospective analysis of long-term outcomes and factors influencing early and late results of a 20-year experience with open repair of atherosclerotic pararenal abdominal aortic aneurysms (PAAAs). METHODS: Records of consecutive patients who underwent open repair of PAAA between 1990 and 2010 at a tertiary referral care center were analyzed for demographics, comorbidities, operative variables, complications, and 30-day mortality. Long term results were also assessed through a local electronic medical database and direct follow-up. Variables influencing early and late results were evaluated by univariate and multivariate logistic regression analyses, stepwise backward elimination, and Cox proportional hazard regression. RESULTS: The study included 200 patients (94% men; mean age, 69.5 years) who were monitored for a mean of 107.3 months. The aneurysm was juxtarenal in 78% of patients, suprarenal in 19.5%, and type IV thoracoabdominal in 2.5%. Mortality at 30 days was 2.5%. At least one major complication occurred in 51.5%. Postoperative acute renal failure (pARF) occurred in 11% of the patients, 3% had temporary hemodialysis, but only 0.5% required chronic hemodialysis. pARF was significantly related to preoperative renal function (P = .009), visceral ischemia >30 minutes (P = .05), and supraceliac or supramesenteric clamp site (P = .005). Respiratory complications (13.8%) were associated with an increasing stage of chronic obstructive pulmonary disease (P = .020), proximal clamp site (P = .047), and intraoperatively infused crystalloids (P = .014). Cardiac complications (12.8%) were related to previous myocardial infarction (P = .031) and proximal clamp site (P = .003). Late deaths were observed in 21.5%. Mean survival was 50 months, with Kaplan-Meier survival estimates of 78% at 5 years and 60.5% at 10 years. Variables influencing long-term survival included age (hazard ratio [HR], 2.67; P = .01), chronic obstructive pulmonary disease stage 2 (HR, 5.14; P = .01) and stage 3 (HR, 4.54; P = .03), postoperative cardiac complication (HR, 3.93; P <= .00), previous myocardial infarction (HR, 1.47; P = .02), peripheral artery disease (HR, 1.97; P = .03), and smoking (HR, 1.17; P = .02). Survival and late onset renal insufficiency were unaffected by preoperative renal function. Late renal failure was observed in 6.2% of the patients but did not predict mortality. CONCLUSIONS: Conventional surgical repair of PAAAs can be performed with acceptable short-term and long-term mortality. Although pARF is frequent, chronic hemodialysis at discharge is rare. Cardiac and respiratory complications are also common and associated with worse survival. Our data represent a potentially useful benchmark for complex endovascular repairs of this type of aneurysm. PMID- 26994950 TI - Flexible robotics with electromagnetic tracking improves safety and efficiency during in vitro endovascular navigation. AB - OBJECTIVE: One limitation of the use of robotic catheters is the lack of real time three-dimensional (3D) localization and position updating: they are still navigated based on two-dimensional (2D) X-ray fluoroscopic projection images. Our goal was to evaluate whether incorporating an electromagnetic (EM) sensor on a robotic catheter tip could improve endovascular navigation. METHODS: Six users were tasked to navigate using a robotic catheter with incorporated EM sensors in an aortic aneurysm phantom. All users cannulated two anatomic targets (left renal artery and posterior "gate") using four visualization modes: (1) standard fluoroscopy mode (control), (2) 2D fluoroscopy mode showing real-time virtual catheter orientation from EM tracking, (3) 3D model of the phantom with anteroposterior and endoluminal view, and (4) 3D model with anteroposterior and lateral view. Standard X-ray fluoroscopy was always available. Cannulation and fluoroscopy times were noted for every mode. 3D positions of the EM tip sensor were recorded at 4 Hz to establish kinematic metrics. RESULTS: The EM sensor incorporated catheter navigated as expected according to all users. The success rate for cannulation was 100%. For the posterior gate target, mean cannulation times in minutes:seconds were 8:12, 4:19, 4:29, and 3:09, respectively, for modes 1, 2, 3 and 4 (P = .013), and mean fluoroscopy times were 274, 20, 29, and 2 seconds, respectively (P = .001). 3D path lengths, spectral arc length, root mean dimensionless jerk, and number of submovements were significantly improved when EM tracking was used (P < .05), showing higher quality of catheter movement with EM navigation. CONCLUSIONS: The EM tracked robotic catheter allowed better real time 3D orientation, facilitating navigation, with a reduction in cannulation and fluoroscopy times and improvement of motion consistency and efficiency. PMID- 26994949 TI - Anesthetic type and risk of myocardial infarction after carotid endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). AB - OBJECTIVE: Carotid endarterectomy (CEA) is usually performed under general anesthesia (GA), although some advocate regional anesthesia (RA) to reduce hemodynamic instability and allow neurologic monitoring and selective shunting. RA does not reduce risk of periprocedural stroke or death, although some series show a reduction in myocardial infarction (MI). We investigated the association of anesthesia type and periprocedural MI among patients receiving GA or RA for CEA and patients undergoing carotid artery stenting (CAS) in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). METHODS: Between 2000 and 2008, 1151 patients underwent CEA (anesthetic type available for 1149 patients), and 1123 patients underwent CAS <=30 days of randomization in CREST. CEA patients were categorized by anesthetic type (GA vs RA). CREST defined protocol MI as chest pain or electrocardiogram change plus biomarker evidence of MI, and total MI was defined as protocol MI plus biomarker-positive (+)-only MI. The incidence of protocol MI and total MI in patients undergoing CEA under GA and RA were compared with those undergoing CAS. Other study end points were similarly compared. Differences in baseline characteristics and periprocedural events were evaluated among the three groups. Logistic regression, adjusting for age and symptomatic status, was used to assess group differences. RESULTS: The three groups had similar demographic risk factors, except for prevalence of symptomatic carotid stenosis, which was lowest in the CEA-RA group (P = .03). Of the 111 patients in the CEA-RA group, no protocol MIs occurred and only two biomarker+ only MIs, for an overall incidence of 1.8%, similar to the 1.7% overall incidence in patients undergoing CAS. In contrast, the combined incidence of protocol and biomarker+-only MIs in the 1038 patients in the CEA-GA group was significantly higher at 3.4% (P = .04), twice the risk of protocol MI and biomarker+-only MI compared with those undergoing CAS (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.14-3.54). Direct comparison of the MI incidence between CEA-RA and CEA-GA showed no statistical difference. Patients undergoing CEA-GA had lower odds of a periprocedural stroke (OR, 0.48; 95% CI, 0.28-0.79) and stroke or death (OR, 0.46; 95% CI, 0.27-0.76) compared with those undergoing CAS but were not significantly different from those undergoing CEA-RA. CONCLUSIONS: Patients in CREST undergoing CEA-RA had a similar risk of periprocedural MI as those undergoing CAS, whereas the risk for CEA-GA was twice that compared with patients undergoing CAS. Nevertheless, because periprocedural MI is one of the few variables favoring CAS over CEA and has been associated with decreased long-term survival, RA should be seriously considered for patients undergoing CEA. PMID- 26994951 TI - Systemic and cell-specific mechanisms of vasculopathy induced by human immunodeficiency virus and highly active antiretroviral therapy. AB - OBJECTIVE: Patients infected with human immunodeficiency virus (HIV) have higher rates of dyslipidemia, atherosclerosis, and chronic inflammation that can damage the vascular system compared with the general population. This can be attributed both to HIV itself and to highly active antiretroviral therapy (HAART) they receive. This review outlines the mechanisms by which HIV and HIV medications can cause vascular complications and identifies strategic areas of research to treat these dysfunctions. REVIEW: HIV and HAART affect the vascular system through several mechanisms that target systemic or metabolic systems and specific cells. HIV causes dyslipidemia and chronic immune activation, which can contribute to atherosclerosis. In addition, HIV damages macrophages, endothelial cells, smooth muscle cells, and platelets, and this damage also plays a role in the development of atherosclerosis. HAART, particularly protease inhibitors, interferes with cholesterol metabolism and can affect macrophages, endothelial cells, and smooth muscle cells. The metabolic changes and cell damage induced by HIV and HAART put HIV patients at increased risk for atherosclerosis, dyslipidemia, and serious cardiovascular events such as myocardial infarction and stroke. CONCLUSIONS: HIV patients have increased risk of developing potentially life-threatening cardiovascular pathology, which cannot be explained by traditional cardiovascular risk factors alone. More research is needed into therapies to target this HIV specific vasculopathy. PMID- 26994952 TI - The evidence-based surgical anatomy of the popliteal artery and the variations in its branching patterns. AB - OBJECTIVE: The goal of our study was to analyze the prevalence of branching pattern variations in the popliteal artery (PA) along with morphometrics of the PA to better address its importance in disease and vascular surgical procedures. METHODS: An extensive search for the PA and its anatomic variations was done in the major online medical databases. The anatomic data found were extracted and pooled for a meta-analysis. RESULTS: A total of 33 studies (N = 12,757 lower limbs) were included in the analysis. The most common variant was a division of the PA below the knee into the anterior tibial artery and a common trunk for the posterior tibial and peroneal arteries, with a prevalence of 92.6% (95% confidence interval [CI], 90.2-93.8). The second most common variation was a trifurcation pattern of all three branches dividing within 0.5 cm of each other, with a prevalence of 2.4% (95% CI, 1.4-3.5). Of the three studies that reported the diameter of the PA at the level of the subcondylar plane, a mean diameter of 8 mm (95% CI, 7.29-8.70) was found. CONCLUSIONS: The PA most commonly divides below the knee into the anterior tibial artery and the common trunk of the posterior tibial artery and the peroneal artery. Knowledge of the prevalence of possible variations in this anatomy as well as morphometric data is crucial in the planning and execution of any surgical intervention in the area of the knee. PMID- 26994953 TI - Low-profile versus standard-profile multibranched thoracoabdominal aortic stent grafts. AB - OBJECTIVE: This study compared midterm results using low-profile stent grafts (LPSGs; 18F) and standard-profile stent grafts (SPSGs; 22F-24F) for endovascular pararenal and thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: From July 2005 to March 2015, 134 asymptomatic patients underwent endovascular repair of a pararenal or TAAA using multibranched aortic stent grafts. In March 2011, we started using a LPSG with nitinol stents and thin-walled polyester fabric. Prospectively collected data on operative repair, complications, and outcomes were compared between the two groups. RESULTS: LPSGs were used in 37 patients (8 women [21.6%]; mean +/- standard deviation age, 72.5 +/- 8 years) and SPSGs in 97 patients (25 [26%] women; mean age, 73 +/- 8 years). Medical comorbidities, aneurysm size, and aneurysm extent were similar in the LPSG and SPSG groups. Mean follow-up time was longer in the SPSG group (3.1 +/- 2 years) than in the LPSG group (1.3 +/- 0.9 years; P < .001). Operative time, renal failure, stroke, myocardial infarction, and perioperative death were not significantly different between the two groups (P > .05). Aneurysm-related death, rupture, stent graft migration, type I or III endoleaks, aneurysm enlargement >5 mm, branch vessel occlusion, and reintervention rates were similar between the two groups (P > .05). However, the combined outcome of conduit use or access artery injury occurred at a lower rate in the LPSG group than in the SPSG group (16% vs 36%; P = .03). Women experienced significantly higher rates of conduit use and access artery injury than men after repair with SPSGs (64% vs 26%, respectively; P = .001) but similar rates after repair with the LPSG (25% vs 14%, respectively; P = .45). CONCLUSIONS: LPSGs had similar safety profile and midterm outcomes compared with the SPSGs for treatment of pararenal and TAAA. The substitution of LPSGs for SPSGs lowered the number of patients who required conduit insertion to avoid access artery injury, especially in women, thereby reducing an otherwise striking gender difference. PMID- 26994954 TI - Transperitoneal versus retroperitoneal approach for open abdominal aortic aneurysm repair in the targeted vascular National Surgical Quality Improvement Program. AB - OBJECTIVE: We sought to compare current practices in patient selection and 30-day outcomes for transperitoneal and retroperitoneal abdominal aortic aneurysm (AAA) repairs. METHODS: All patients undergoing elective transperitoneal or retroperitoneal surgical repair for AAA between January 2011 and December 2013 were identified in the Targeted Vascular National Surgical Quality Improvement Program database. Emergency cases were excluded. Baseline characteristics, anatomic details, and intraoperative and postoperative outcomes were evaluated among those with infrarenal or juxtarenal AAA only. RESULTS: We identified 1135 patients: 788 transperitoneal (69%) and 347 retroperitoneal (31%). When only infrarenal and juxtarenal AAAs were evaluated, the retroperitoneal patients were less likely to have an infrarenal clamp location (43% vs 68%) and had more renal revascularizations (15% vs 6%; P < .001), more visceral revascularizations (5.6% vs 2.4%; P = .014), and more lower extremity revascularizations (11% vs 7%; P = .021) compared with the transperitoneal approach. Postoperative mortality and return to the operating room were similar. Transperitoneal patients had a higher rate of wound dehiscence (2.4% vs 0.4%; P = .045), and retroperitoneal patients had higher incidence of pneumonia (9% vs 5%; P = .034), transfusion (77% vs 71%; P = .037), and reintubation (11% vs 7%; P = .034), and a longer median length of stay (8 vs 7 days; P = .048). After exclusion of all concomitant procedures, only transfusions remained more common in the retroperitoneal approach (78% vs 70%; P = .036). Multivariable analyses showed only higher rates of reintubation in the retroperitoneal group (odds ratio, 1.7; 95% confidence interval, 1.0-3.0; P = .047). CONCLUSIONS: The retroperitoneal approach is more commonly used for more proximal aneurysms and was associated with higher rates of pneumonia, reintubation, and transfusion, and a longer length of stay on univariate analyses. However, multivariable analysis demonstrated similar results between groups. The long-term benefits and frequency of reinterventions remain to be proven. PMID- 26994955 TI - The effect of intercostal artery reimplantation on spinal cord injury in thoracoabdominal aortic aneurysm surgery. AB - OBJECTIVE: Intercostal artery (ICA) reimplantation (ICAR) is thought to decrease spinal cord injury (SCI) in thoracic aortic aneurysm and thoracoabdominal aortic aneurysm (TAAA) surgery. Patients treated from 1989 to 2005 without ICAR were compared with those treated from 2005 to 2013 with ICAR to determine whether ICAR reduced SCI. We hypothesized that ICAR would reduce SCI, especially in the highest-risk patients. METHODS: This was a retrospective analysis using a prospectively maintained Investigational Review Board-approved database from a university tertiary referral center. The analysis included all patients (n = 805) undergoing thoracic aortic aneurysm and TAAA surgery from 1989 to 2013. The main outcome measure was any transient or permanent paraplegia or paraparesis (SCI). From 1989 to 2004, ICAR was not performed in patients, and open ICAs were ligated; from 2005 to 2013, open ICAs at T7 to L2 were reimplanted in patients with Crawford type I, II, and III TAAAs. Surgical technique was cross clamp without assisted circulation. Anesthetic management was the same from 1989 to 2013. Demographic, intraoperative, and outcome variables were assessed by univariate and multivariate analysis. Observed/expected ratios for paralysis were calculated. RESULTS: A total of 540 patients had surgery before 2005, and 265 had surgery after 2005, when ICAR was begun. There were 275 type I, II, and III TAAAs before 2005 and 164 after 2005. Aneurysm extent, acuity, SCI, mortality, renal failure, and pulmonary failure were the same in patients treated before and after 2005. Multivariate modeling of all patients showed type II TAAA (P = .0001), dissection (P = .00015), and age as a continuous variable (P = .0085) were significant for SCI. Comparing only type I, II, and III TAAAs, there was no difference in SCI between those with ICAR after 2005 and those without ICAR before 2005 (5.1% vs 8.8%; P = .152). In a subanalysis of the highest-risk patients (type II, dissection, acute), ICAR was not significant (P = .27). Observed/expected ratios ratios were 0.23 before 2005 and 0.16 after 2005 (chi2 = .796; P = .37). CONCLUSIONS: Although there was a small decrease in SCI with ICAR, reattaching ICAs did not produce a statistically significant reduction in SCI, even in the highest-risk patients. PMID- 26994956 TI - Late single-center outcome of the Talent Abdominal Stent Graft after a decade of follow-up. AB - OBJECTIVE: Lifelong yearly surveillance is advised after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms. This follow-up requires a substantial amount of health care resources. The aim of this paper was to assess the occurrence of stent graft-related complications and secondary interventions during a minimum 10-year follow-up after elective EVAR. METHODS: Patients who were treated in a high-volume endovascular center in The Netherlands with the Talent infrarenal stent graft (Medtronic Vascular, Santa Rosa, Calif) between June 1999 and February 2005 were included. Patients with previous aortic surgery or emergency interventions were excluded. Our primary outcome was clinical success up to 10 years. Secondary end points were technical success and survival. RESULTS: A total of 149 patients were included; 91.9% were male. The mean age was 70.2 +/- 7.8 years. A stent graft was implanted in 98% of patients; technical success was achieved in 89.9%. Clinical success after 30 days, 1 year, 5 years, and 10 years was 81.1%, 74.3%, 70.3%, and 65.5%, respectively. In 30 patients (20.7%), a secondary intervention was required; 80.0% of first secondary interventions occurred within the first 5 years. Six late conversions were necessary because of stent graft infection (2), migration (2), or persisting endoleak (2). The 5- and 10-year overall survival rates were 55.2% and 38.6%, respectively. CONCLUSIONS: The risk of EVAR-related complication is highest in the first 5 years. Consequently, the main focus should be on that period; further follow-up must not be neglected, as complications occur up to 10 years after treatment. PMID- 26994957 TI - The role of Model for End-Stage Liver Disease (MELD) score in predicting outcomes for lower extremity bypass. AB - OBJECTIVE: The Model for End-Stage Liver Disease (MELD) score has traditionally been used to prioritize liver transplantation. However, its use has been extended to predict overall and postoperative outcomes in patients with hepatic and renal dysfunction. Our objective was to use the MELD score to predict outcomes in patients undergoing lower extremity bypass. METHODS: Patients undergoing infrainguinal bypass were identified in the American College of Surgeons National Surgical Quality Improvement Program data sets from 2005 to 2012. The MELD score was calculated using serum bilirubin and creatinine values and the international normalized ratio. Patients were grouped into low (<9), moderate (9-14), and high (15+) MELD classifications. The associations of the MELD score on postoperative morbidity and mortality were assessed by multivariable logistic and gamma regressions and by propensity matching. RESULTS: There were 5967 patients who underwent infrainguinal bypass with the following MELD score distribution: <9, 3795 (64%); 9 to 14, 1819 (30%); and 15+, 353 (6%). Matched analysis in comparing low, moderate, and high MELD scores showed a higher risk for cardiac complications (2.8% vs 3.2% vs 5.4%; P < .001), bleeding complications (9.3% vs 11.1% vs 13.9%; P = .048), and increased postoperative length of stay (median [range], 5 [0-93] vs 6 [0-73] vs 6 [0-86]; P < .001). The MELD score had no association with early bypass failure, wound complications, or operative time. Moderate and high MELD scores were independent predictors of postoperative myocardial infarction/cardiac arrest (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.6-3.6; P < .001; and OR, 4.1; 95% CI, 2.3-7.3; P < .01), bleeding complications (OR, 1.3; 95% CI, 1.1-1.6; P < .01; and OR, 1.8; 95% CI, 1.3-2.5; P < .01), return to the operating room (OR, 1.3; 95% CI, 1.1-1.5; P < .01; and OR, 1.4; 95% CI, 1.03-1.8; P = .03), extended postoperative length of stay (means ratio, 1.2; 95% CI, 1.1-1.2; P < .01; and means ratio, 1.2; 95% CI, 1.2-1.3; P < .01), and perioperative mortality (OR, 1.6; 95% CI, 1.02-2.5; P = .04; and OR, 2.9; 95% CI, 1.6-5.4; P = .01), respectively. Propensity matching between low, moderate, and high MELD score groups confirmed an increased risk of postoperative myocardial infarction/cardiac arrest (P < .01), bleeding complications (P = .05), and extended postoperative length of stay (P < .01) with a trend toward increased mortality and return to operating room. CONCLUSIONS: An elevated MELD score places patients undergoing infrainguinal bypass at higher risk of perioperative morbidity and mortality. This provides an evidence base for risk stratification and informed consent for these patients. Alternative treatment may be considered in these patients; however, the overall morbidity and mortality rates may still be acceptable, even in high-risk patients. PMID- 26994958 TI - Validation of the Wound, Ischemia, foot Infection (WIfI) classification system in nondiabetic patients treated by endovascular means for critical limb ischemia. AB - BACKGROUND: The Society for Vascular Surgery Lower Extremity Guidelines Committee developed the Wound, Ischemia, foot Infection (WIfI) a classification system to predict the amputation risk in patients with critical limb ischemia (CLI). A number of published studies have already evaluated its prognostic value. However, most of the included patients were diabetic, and the validation was done independent of the revascularization procedure. This single-center study evaluated the prognostic value of WIfI stages in nondiabetic patients treated by endovascular means. METHODS: A retrospective analysis was performed of prospectively collected data of nondiabetic patients treated by endovascular means between January 2013 and September 2014. All patients were classified according to their wound status, ischemia index, and extent of foot infection to four classes: very low risk, low risk, moderate risk, and high risk. Comorbidities and vascular lesions for each group were analyzed. The prognostic value of WIfI was analyzed based on the amputation-free survival, overall survival rate, and freedom from amputation at 12 months. RESULTS: Data from 302 CLI patients treated in the study period were reviewed. A total of 219 patients (73%) underwent an endovascular intervention, and among them, 126 nondiabetic patients (58%) were enrolled in this study. Most patients were classified as low risk (33%), and the prevalence of very low-risk, moderate-risk, and very high risk patients was 23%, 23%, and 21%, respectively. The modified Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT III) score was statistically significantly higher in the high-risk group (5.2 +/- 2.4) than in the very low-risk, low-risk, and moderate-risk groups (4.3 +/- 2.5, 3.5 +/- 2.3, 4.5 +/- 2.2, respectively; P = .048). One major amputation (1%) was performed during the hospital stay in a high-risk patient. Mean follow-up was 14 +/- 8 months. The amputation-free survival at 12 months was 87%, 81%, 81%, and 62%, in the very low-risk, low-risk, moderate risk, and very high-risk groups, respectively (P = .106). The difference was statistically significant between the very low-risk and high-risk groups (hazard ratio, 3.4; 95% confidence interval, 1.1-10.3; P = .029). A similar trend was also observed for 1-year survival between the very low-risk and the high-risk groups (87%, 84%, 81%, 65%; P = .166). The amputation rate during the follow-up time was 0%, 2% (n = 6), 3% (n = 5), and 12% (n = 9) for the very low-risk, low-risk, moderate-risk, and very high risk groups, respectively (P = .033). CONCLUSIONS: The WIfI classification system predicted the amputation risk and survival in this highly selected group of nondiabetic CLI patients treated by endovascular means, with a statistically significant difference between very low-risk and high-risk patients already at 1 year. PMID- 26994959 TI - SPY technology as an adjunctive measure for lower extremity perfusion. AB - OBJECTIVE: Lack of a reliable outcome measure often leads to excessive or insufficient interventions for critical limb ischemia (CLI). SPY technology (Novadaq Technologies Inc, Bonita Springs, Fla), widely adapted by plastic and general surgeons, uses laser-assisted fluorescence angiography (LAFA) to assess tissue perfusion. We sought to determine the role of SPY as an alternative, perhaps more reliable outcome measure for vascular interventions. METHODS: All patients undergoing elective or urgent revascularization for claudication and CLI were prospectively recruited from June 2012 to August 2014. LAFA using SPY technology was performed before and after revascularization procedures under a standard Institutional Review Board-approved protocol. Quantitative measures of perfusion at plantar surfaces were analyzed and compared with ankle-brachial index. RESULTS: A total of 93 patients with claudication or CLI underwent LAFA before and after a revascularization procedure in the study period. The mean preoperative ankle-brachial index increased from 0.60 to 0.84 (P < .001) after a revascularization procedure. Plantar perfusion as measured by LAFA also improved significantly after intervention. Ingress, defined as the rate at which fluorescence intensity increases on the plantar surface during LAFA, increased from 7.1 to 12.4 units/s (P < .001). Peak perfusion, defined as the difference between the baseline and the peak of fluorescence intensity, increased from 97.1 and 143.9 units (P < .001). Egress, defined as the rate at which intensity diminishes after reaching peak perfusion, increased from 1.0 to 1.9 units/s (P = .035). Procedure-related digital embolization was also observed in several patients despite lack of an angiographic finding. CONCLUSIONS: This is the largest prospective study evaluating SPY technology in peripheral vascular interventions. Our study shows that SPY is a valuable tool in visualizing real time procedural outcomes and providing additionally useful information on regional tissue perfusion. Further investigation is warranted to standardize outpatient use and to determine threshold values that predict wound healing. PMID- 26994961 TI - Reproductive history and post-reproductive mortality: A sibling comparison analysis using Swedish register data. AB - A growing body of evidence suggests that reproductive history influences post reproductive mortality. A potential explanation for this association is confounding by socioeconomic status in the family of origin, as socioeconomic status is related to both fertility behaviours and to long-term health. We examine the relationship between age at first birth, completed parity, and post reproductive mortality and address the potential confounding role of family of origin. We use Swedish population register data for men and women born 1932-1960, and examine both all-cause and cause-specific mortality. The contributions of our study are the use of a sibling comparison design that minimizes residual confounding from shared family background characteristics and assessment of cause specific mortality that can shed light on the mechanisms linking reproductive history to mortality. Our results were entirely consistent with previous research on this topic, with teenage first time parents having higher mortality, and the relationship between parity and mortality following a U-shaped pattern where childless men and women and those with five or more children had the highest mortality. These results indicate that selection into specific fertility behaviours based upon socioeconomic status and experiences within the family of origin does not explain the relationship between reproductive history and post reproductive mortality. Additional analyses where we adjust for other lifecourse factors such as educational attainment, attained socioeconomic status, and post reproductive marital history do not change the results. Our results add an important new level of robustness to the findings on reproductive history and mortality by showing that the association is robust to confounding by factors shared by siblings. However it is still uncertain whether reproductive history causally influences health, or whether other confounding factors such as childhood health or risk-taking propensity could explain the association. PMID- 26994960 TI - Clinical features of JAK2V617F- or CALR-mutated essential thrombocythemia and primary myelofibrosis. PMID- 26994962 TI - Moderate malnutrition in rats induces somatic gene mutations. AB - The relationship between malnutrition and genetic damage has been widely studied in human and animal models, leading to the observation that interactions between genotoxic exposure and micronutrient status appear to affect genomic stability. A new assay has been developed that uses the phosphatidylinositol glycan class A gene (Pig-a) as a reporter for measuring in vivo gene mutation. The Pig-a assay can be employed to evaluate mutant frequencies (MFs) in peripheral blood reticulocytes (RETs) and erythrocytes (RBCs) using flow cytometry. In the present study, we assessed the effects of malnutrition on mutagenic susceptibility by exposing undernourished (UN) and well-nourished (WN) rats to N-ethyl-N nitrosourea (ENU) and measuring Pig-a MFs. Two week-old UN and WN male Han-Wistar rats were treated daily with 0, 20, or 40mg/kg ENU for 3 consecutive days. Blood was collected from the tail vein one day before ENU treatment (Day-1) and after ENU administration on Days 7, 14, 21, 28, 35, 42, 49, 56 and 63. Pig-a MFs were measured in RETs and RBCs as the RET(CD59-) and RBC(CD59-) frequencies. In the vehicle control groups, the frequencies of mutant RETs and RBCs were significantly higher in UN rats compared with WN rats at all sampling times. The ENU treatments increased RET and RBC MFs starting at Day 7. Although ENU-induced Pig-a MFs were consistently lower in UN rats than in WN rats, these differences were not significant. To understand these responses, further studies should use other mutagens and nucleated surrogate cells and examine the types of mutations induced in UN and WN rats. PMID- 26994963 TI - A review on emerging frontiers of house dust mite and cockroach allergy research. AB - Currently, mankind is afflicted with diversified health issues, allergies being a common, yet little understood malady. Allergies, the outcome of a baffled immune system encompasses myriad allergens and causes an array of health consequences, ranging from transient to recurrent and mild to fatal. Indoor allergy is a serious hypersensitivity in genetically-predisposed people, triggered by ingestion, inhalation or mere contact of allergens, of which mite and cockroaches are one of the most-represented constituents. Arduous to eliminate, these aeroallergens pose constant health challenges, mostly manifested as respiratory and dermatological inflammations, leading to further aggravations if unrestrained. Recent times have seen an unprecedented endeavour to understand the conformation of these allergens, their immune manipulative ploys and other underlying causes of pathogenesis, most importantly therapies. Yet a large section of vulnerable people is ignorant of these innocuous-looking immune irritants, prevailing around them, and continues to suffer. This review aims to expedite this field by a concise, informative account of seminal findings in the past few years, with particular emphasis on leading frontiers like genome-wide association studies (GWAS), epitope mapping, metabolomics etc. Drawbacks linked to current approaches and solutions to overcome them have been proposed. PMID- 26994965 TI - MISIS-2: A bioinformatics tool for in-depth analysis of small RNAs and representation of consensus master genome in viral quasispecies. AB - In most eukaryotes, small RNA (sRNA) molecules such as miRNAs, siRNAs and piRNAs regulate gene expression and repress transposons and viruses. AGO/PIWI family proteins sort functional sRNAs based on size, 5'-nucleotide and other sequence features. In plants and some animals, viral sRNAs are extremely diverse and cover the entire viral genome sequences, which allows for de novo reconstruction of a complete viral genome by deep sequencing and bioinformatics analysis of viral sRNAs. Previously, we have developed a tool MISIS to view and analyze sRNA maps of viruses and cellular genome regions which spawn multiple sRNAs. Here we describe a new release of MISIS, MISIS-2, which enables to determine and visualize a consensus sequence and count sRNAs of any chosen sizes and 5' terminal nucleotide identities. Furthermore we demonstrate the utility of MISIS-2 for identification of single nucleotide polymorphisms (SNPs) at each position of a reference sequence and reconstruction of a consensus master genome in evolving viral quasispecies. MISIS-2 is a Java standalone program. It is freely available along with the source code at the website http://www.fasteris.com/apps. PMID- 26994964 TI - Epitope-based recombinant diagnostic antigen to distinguish natural infection from vaccination with hepatitis A virus vaccines. AB - Hepatitis A virus (HAV) infection can stimulate the production of antibodies to structural and non-structural proteins of the virus. However, vaccination with an inactivated or attenuated HAV vaccine produces antibodies mainly against structural proteins, whereas no or very limited antibodies are produced against the non-structural proteins. Current diagnostic assays to determine exposure to HAV, such as the Abbott HAV AB test, detect antibodies only to the structural proteins and so are not able to distinguish a natural infection from vaccination with an inactivated or attenuated virus. Here, we constructed a recombinant tandem multi-epitope diagnostic antigen (designated 'H1') based on the immune dominant epitopes of the non-structural proteins of HAV to distinguish the two situations. H1 protein expressed in Escherichia coli and purified by affinity and anion exchange chromatography was applied in a double-antigen sandwich ELISA for the detection of anti-non-structural HAV proteins, which was confirmed to distinguish a natural infection from vaccination with an inactivated or attenuated HAV vaccine. PMID- 26994966 TI - Complementary assays for monitoring susceptibility of varicella-zoster virus resistance to antivirals. AB - The emergence of varicella-zoster virus (VZV) resistance to current antivirals as acyclovir (ACV) constitutes a hindrance to antiviral treatment effectiveness of VZV infections, especially in immunocompromised patients. The molecular mechanisms of VZV resistance reported so far rely on the presence of mutations within thymidine kinase (TK, ORF36) and DNA polymerase (ORF28) viral genes. The aim of this work was to develop reliable and complementary diagnostic methods to detect VZV antiviral resistance: (i) a genotypic assay based on TK and DNA polymerase genes sequencing, (ii) a plaque reduction assay to determine antiviral 50% effective concentrations, and (iii) a functional assay to evaluate in vitro phosphorylation activity of recombinant TKs. As a whole, this study included the analysis of 21 VZV clinical isolates and 62 biological samples from patients experiencing VZV infection. Genetic analysis revealed 3 and 9 new amino acid changes that have not been previously described within the highly conserved TK and DNA polymerase, respectively. Then, VZV isolates bearing newly identified mutations considered as natural polymorphisms were characterized as susceptible to ACV using plaque-reduction assay in MeWo cells. In parallel, the impact of TK changes on ACV phosphorylation activity was examined using a nonradioactive in vitro enzymatic assay. PMID- 26994967 TI - Gene-Corrected Fibroblast Therapy for Recessive Dystrophic Epidermolysis Bullosa using a Self-Inactivating COL7A1 Retroviral Vector. AB - Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack type VII collagen and therefore have severely impaired dermal-epidermal stability causing recurrent skin and mucosal blistering. There is currently no specific approved treatment for RDEB. We present preclinical data showing that intradermal injections of genetically corrected patient-derived RDEB fibroblasts using a Good Manufacturing Practices grade self-inactivating COL7A1 retroviral vector reverse the disease phenotype in a xenograft model in nude mice. We obtained 50% transduction efficiency in primary human RDEB fibroblasts with an average low copy number (range = 1-2) of integrated provirus. Transduced fibroblasts showed strong type VII collagen re-expression, improved adhesion properties, normal proliferative capabilities, and viability in vitro. We show that a single intradermal injection of 3 * 10(6) genetically corrected RDEB fibroblasts beneath RDEB skin equivalents grafted onto mice allows type VII collagen deposition, anchoring fibril formation at the dermal-epidermal junction, and improved dermal epidermal adherence 2 months after treatment, supporting functional correction in vivo. Gene-corrected fibroblasts previously showed no tumorigenicity. These data show the efficacy and safety of gene-corrected fibroblast therapy using a self inactivating vector that has now been good manufacturing grade-certified and pave the way for clinical translation to treat nonhealing wounds in RDEB patients. PMID- 26994968 TI - Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development. AB - Polycomb repressive complex 2 (PRC2) is an essential regulator of cell physiology. Although there have been numerous studies on PRC2 function in somatic tissue development and stem cell control, these have focused on the loss of a single PRC2 subunit. Recent studies, however, have shown that PRC2 subunits may function independently of the PRC2 complex. To investigate the function of PRC2 in the control of skin development, we generated and analyzed three conditional knockout mouse lines, in which the essential PRC2 subunits embryonic ectoderm development (EED), suppressor of zeste 12 homolog (Suz12), and enhancer of zeste homologs 1 and 2 (Ezh1/2) are conditionally ablated in the embryonic epidermal progenitors that give rise to the epidermis, hair follicles, and Merkel cells. Our studies showed that the observed loss-of-function phenotypes are shared between the three knockouts, indicating that in the skin epithelium, EED, Suz12, and Ezh1/2 function largely as subunits of the PRC2 complex. Interestingly, the absence of PRC2 results in dramatically different phenotypes across the different skin lineages: premature acquisition of a functional epidermal barrier, formation of ectopic Merkel cells, and defective postnatal development of hair follicles. The strikingly different roles of PRC2 in the formation of three lineages exemplify the complex outcomes that the lack of PRC2 can have in a somatic stem cell system. PMID- 26994969 TI - The Transient Role for Calcium and Vitamin D during the Developmental Hair Follicle Cycle. AB - The role for 1,25-dihydroxyvitamin D3 and/or calcium in hair follicle cycling is not clear despite their impact on keratinocyte differentiation. We found that calbindin-D9k null (knockout) pups generated from calbindin-D9k knockout females fed a vitamin D-deficient, low-calcium (0.47%) diet develop transient alopecia. The pups appear phenotypically normal until 13 days of age, after which the hair progressively sheds in a caudocephalic direction, resulting in truncal alopecia totalis by 20-23 days, with spontaneous recovery by 28 days. Histological studies showed markedly dystrophic hair follicles, loss of hair shafts with increased apoptosis, and hyperplastic epidermis during this time. Ha1 expression is lost during catagen in all mice but recovers more slowly in the knockout pups on the vitamin D-deficient, low-calcium diet. Keratin 1 expression is reduced throughout days 19-28. The expressions of involucrin, loricrin, and cathepsin L is initially increased by day 19 but subsequently falls below those of controls by day 23, as does that of desmoglein 3. Feeding the mothers a high-vitamin D/high-calcium (2%)/lactose (20%) diet lessens the phenotype, and knockout pups fostered to mothers fed a normal diet do not develop alopecia. Our results show that in calbindin-D9k knockout pups, a maternal vitamin D-deficient/low-calcium diet leads to transient noncicatricial alopecia. PMID- 26994970 TI - Paper recycling framework, the "Wheel of Fiber". AB - At present, there is no reliable method in use that unequivocally describes paper industry material flows and makes it possible to compare geographical regions with each other. A functioning paper industry Material Flow Account (MFA) that uses uniform terminology and standard definitions for terms and structures is necessary. Many of the presently used general level MFAs, which are called frameworks in this article, stress the importance of input and output flows but do not provide a uniform picture of material recycling. Paper industry is an example of a field in which recycling plays a key role. Additionally, terms related to paper industry recycling, such as collection rate, recycling rate, and utilization rate, are not defined uniformly across regions and time. Thus, reliably comparing material recycling activity between geographical regions or calculating any regional summaries is difficult or even impossible. The objective of this study is to give a partial solution to the problem of not having a reliable method in use that unequivocally describes paper industry material flows. This is done by introducing a new material flow framework for paper industry in which the flow and stage structure supports the use of uniform definitions for terms related to paper recycling. This new framework is termed the Detailed Wheel of Fiber. PMID- 26994971 TI - A Rare and Exclusive Endoperoxide Photoproduct Derived from a Thiacalix[4]arene Crown-Shaped Derivative Bearing a 9,10-Substituted Anthracene Moiety. AB - A rare and exclusive endoperoxide photoproduct was quantitatively obtained from a thiacalix[4]arene crown-shaped derivative upon irradiation at lambda=365 nm; the structure was unambiguously confirmed by (1) H/(13) C NMR spectroscopy and X-ray crystallography. The prerequisites for the formation of the endoperoxide photoproduct have also been discussed. Furthermore, the photochemical reaction rate could be greatly enhanced in the presence of the thiacalix[4]arene platform because it served as a host to capture oxygen. PMID- 26994972 TI - Facing disasters. PMID- 26994973 TI - When in doubt, aspirate. AB - Coronary embolization accounts for about 2% of ST elevation myocardial infarctions (STEMI). Thrombus aspiration may be particularly effective in these cases and may prevent the need for coronary stenting. Despite recent guidelines assigning a class III recommendation to routine thrombus aspiration, selective thrombus aspiration based on angiographic appearance may be effective. PMID- 26994974 TI - Efficacy and safety of routine thrombus aspiration in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: An updated systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Randomized clinical trials evaluating the role of thrombus aspiration (TA) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) have yielded contrasting results. Therefore, the efficacy and safety of TA in STEMI is unclear. OBJECTIVE: We sought to evaluate the efficacy and safety of TA during PPCI for STEMI compared with conventional PPCI alone. METHODS: We included study-level data from 25 randomized, controlled trials, involving 21,733 patients with STEMI and PPCI. The primary efficacy endpoint was major adverse cardiac events (MACE) according to study definitions; the primary safety endpoint was stroke. RESULTS: The mean weighted follow-up time across studies was 8.2 months. Compared with conventional PPCI, TA was associated with significant lower risk for MACE [relative risk (RR): 0.91; 95% confidence interval (CI): 0.83-1.00; P = 0.042). However, this benefit in MACE was counterbalanced by a significant increase in the risk for stroke (RR: 1.58; 95% CI: 1.11-2.25; P = 0.011). There were no differences in the risk of myocardial infarction (RR: 0.94; 95% CI: 0.78-1.12; P = 0.486), target vessel revascularization (RR: 0.93; 95% CI: 0.82-1.04; P = 0.2), and definite or probable stent thrombosis (RR: 0.84; 95% CI: 0.66-1.07; P = 0.148). TA was associated with an ostensible lower risk for all-cause mortality, which did not reach statistical significance (RR: 0.88; 95% CI: 0.78-1.00; P = 0.059). CONCLUSIONS: Compared with conventional PPCI for STEMI, adjunctive TA reduces the risk of subsequent MACE. However, the benefit in MACE is counterbalanced by an increased risk in stroke. Considering the above potential risks and benefits, TA should be considered in selected patients lesions rather than routinely. PMID- 26994975 TI - Our aspirations still disappoint. AB - Routine thrombectomy during coronary intervention for STEMI is not supported by two large prospective randomized trials. Occasional case-specific clot removal, while appealing, remains an unproven adjunct to primary stenting during STEMI therapy. While early MACE events may be lower, during follow-up, there is a higher risk of stroke in patients who undergo thrombectomy. PMID- 26994976 TI - Women in interventional cardiology: Is there a problem? AB - In the United States, women account for 4% of interventional cardiologists and perform 3% of interventional procedures. Male and female cardiology fellows share concerns that dissuade them from careers in interventional cardiology; unique issues for women include professional isolation and childbearing. Interventional fellowships should enhance female mentorship and develop friendly policies regarding maternity leave; other issues require comprehensive solutions to medical school debt, duration of training, and balancing professional goals with lifestyle. PMID- 26994977 TI - Orbital atherectomy for severely calcified lesions: More dissections in women but similar 30-day outcomes to men. AB - Calcified lesions are associated with lower rates of successful percutaneous coronary intervention (PCI), greater stent thrombosis, and increased target vessel revascularization. Women undergoing PCI are more often older than men and likely to present with severe lesion calcification. The ORBIT II study, for the first time compares the effect of the orbital atherectomy system (OAS) in men and women undergoing PCI for severely calcified lesions. Although the adjusted risk of severe dissections was higher in women, the incidence of in-hospital and 30 day outcomes was similar to men. Randomized comparisons of the OAS with rotational atherectomy and with stenting without atherectomy are needed to further elucidate sex-based differences in calcified lesion PCI. PMID- 26994978 TI - Don't you forget about me! The 80s still matter! AB - Invasive therapy had a significantly lower odds ratio of death at 28 days in elderly patients. Patients treated with a conservative approach received significantly less guideline directed medical therapy. The highest risk (those most likely to benefit) were less likely to get invasive therapy. PMID- 26994979 TI - Atherectomy for calcified coronary lesions: When and how? AB - Percutaneous coronary intervention of heavily calcified lesions can be challenging. Although the ROTAXUS trial did not demonstrate long-term clinical benefit with routine rotational atherectomy, atherectomy remains an indispensable tool to achieve acute procedural success. Until new data becomes available determining when and how to optimally use coronary atherectomy depends heavily on personal experience and clinical judgment. PMID- 26994980 TI - Can our choice of contrast media impact renal and cardiovascular outcomes? AB - Contrast media vary in their ionic status, viscosity, osmolarity--and these factors all play into clinical effects. Iso-osmolar and low-osmolar contrast media dominate clinical use today. The differences between these two agents in terms of kidney injury remain uncertain. Ionic agents have theoretical properties which may help prevent thrombus formation; however this phenomenon has not translated to differences in clinical outcomes. PMID- 26994981 TI - Back to nature: A more natural alternative to the PTFE covered stent: Twenty-two years in the making. AB - The introduction of easily deployed covered stents has made PCI safer. The homemade venous and PTFE covered stent were effective but not practical for sealing perforations. The novel pericardial covered stent graft goes back to a more natural covering and is more easily deployed. PMID- 26994982 TI - Duration of dual anti-platelet therapy following drug eluting stents: Less Is More? AB - This meta-analysis suggests that abbreviated DAPT (<6 months) could be considered in patients undergoing PCI with current generation drug eluting stents (DES). Extended DAPT strategy (>1 year) may be appropriate in those patients in whom prevention of stent and non-stent-related coronary events are likely to offset the bleeding complications. Additional randomized trials are needed to evaluate the optimum duration of DAPT in patients with the latest generation DES and current antiplatelet drugs. PMID- 26994983 TI - The "open branch" technique: A new way to prevent paraplegia after total endovascular repair of thoracoabdominal aneurysm. AB - Spinal cord ischemia (SCI) has been one of the most concerning complications after surgical and endovascular thoracoabdominal aortic aneurysm repair "Open Branch" is an innovative technique to reduce the incidence of SCI Further studies in a larger number of patients with varying pathologies are needed to confirm the advantages of this technique. PMID- 26994984 TI - Life in the left atrial appendage fast lane after FDA approval: Moving forward on new technology at last. AB - FDA approval of the WATCHMAN is expected to spur development and availability of a range of evolutionary and revolutionary technologies for left atrial appendage occlusion. The fourth generation WATCHMAN described in this article has multiple features that will potentially streamline the deployment process and have the potential to make left atrial appendage occlusion safer. The population studied was too small to compare the relatively high adverse event rate with the known outcomes associated with existing WATCHMAN technology. Going forward, in part because of improvements in technology, it is likely that late ischemic stroke will supplant pericardial effusion as a key outcome measure for ongoing assessment of WATCHMAN safety and efficacy. PMID- 26994985 TI - Is it really "paradoxical" or just the ventricle? AB - Patients with paradoxical low flow low gradient (PLFLG) aortic stenosis (AS) have favorable mid-term outcomes after transcatheter aortic valve replacement (TAVR). These outcomes were comparable to those patients with high gradient AS (HGAS). Clinicians should avoid delaying referral of patients with PLFLG AS for valve replacement for either surgical aortic valve replacement (SAVR) or TAVR. Further studies are need to understand the increased early mortality after TAVR in PLFLG AS compared to HGAS, and to determine whether improvements of TAVR procedural techniques can result in better outcomes. PMID- 26994986 TI - A 41-year-old man with fever and dark-coloured urine. PMID- 26994987 TI - One-year immunogenicity kinetics and safety of a purified chick embryo cell rabies vaccine and an inactivated Vero cell-derived Japanese encephalitis vaccine administered concomitantly according to a new, 1-week, accelerated primary series. AB - BACKGROUND: Conventional rabies pre-exposure prophylaxis (PrEP) and Japanese encephalitis (JE) primary series vaccination regimens each require up to 4 weeks to complete and, thus, may not be feasible for individuals who need these immunizations on short notice. This Phase 3b, randomized, controlled, observer blind study evaluated the immunogenicity and safety of concomitant administration of a purified chick embryo cell culture rabies vaccine and an inactivated, adsorbed JE vaccine according to an accelerated (1 week) regimen when compared with the conventional regimens (4 weeks). This report describes the kinetics of immune responses up to 1 year after vaccination. METHODS: A total of 661 healthy adults (18 to <=65 years) were randomized into the following accelerated or conventional vaccine regimens: Rabies + JE-Conventional, Rabies + JE-Accelerated, Rabies-Conventional and JE-Conventional. Immunogenicity was assessed by virus neutralization tests. Safety and tolerability were also evaluated. RESULTS: Irrespective of rabies vaccination regimen, >=97% of subjects had adequate levels of rabies virus neutralizing antibody (RVNA) concentrations (>=0.5 IU/ml) up to Day 57, with percentages of subjects with RVNA concentrations >=0.5 IU/ml at Day 366 ranging between 68% in the Rabies + JE-Accelerated group and 80% of subjects in the Rabies-Conventional group. The Rabies + JE-Accelerated group revealed high JE neutralizing antibody titers at all-time points. At Day 366, the percentage of subjects with antibody titers indicative of seroprotection (PRNT50 titers >=1:10) remained high across JE vaccine groups (86-94%). CONCLUSIONS: The accelerated PrEP rabies and JE vaccination regimens, once licensed, could represent a valid alternative in the short-term to currently recommended conventional regimens. The concomitant administration of these two vaccines does not compromise immune responses to any of the vaccine antigens particularly when aiming for short-term protection. Further evidence will clarify the need for and timing to administration of rabies vaccine booster doses in subjects primed with an accelerated PrEP regimen. (NCT01662440). PMID- 26994988 TI - Nutrition and Physical Activity Strategies for Cancer Prevention in Current National Comprehensive Cancer Control Program Plans. AB - Obesity, diet and physical inactivity are risk factors for some cancers. Grantees of the National Comprehensive Cancer Control Program (NCCCP) in US states, tribes, and territories develop plans to coordinate funding and activities for cancer prevention and control. Including information and goals related to nutrition and physical activity (NPA) is a key opportunity for primary cancer prevention, but it is currently unclear to what extent NCCCP plans address these issues. We reviewed 69 NCCCP plans and searched for terms related to NPA. Plans were coded as (1) knowledge of NPA and cancer link; (2) goals to improve NPA behaviors; and (3) strategies to increase healthy NPA activities, environments, or systems changes. NPA content was consistently included in all cancer plans examined across all years. Only 4 (6 %) outlined only the relationship between NPA and cancer without goals or strategies. Fifty-nine plans (89 %) contained goals or strategies related to NPA, with 53 (82 %) including both. However, numbers of goals, strategies, and detail provided varied widely. All programs recognized the importance of NPA in cancer prevention. Most plans included NPA goals and strategies. Increasing the presence of NPA strategies that can be modified or adapted appropriately locally could help with more widespread implementation and measurement of NPA interventions. PMID- 26994989 TI - Using Walk ScoreTM and Neighborhood Perceptions to Assess Walking Among Middle Aged and Older Adults. AB - We aimed to determine the relationship between neighborhood characteristics (walkability, cohesion/safety) and recommended activity levels among community dwelling middle-aged and older adults. Subjective and objective data on 394 individuals aged >=50 years were used to assess the likelihood of walking >=150 min/week. Environmental factors associated with a greater likelihood of any walking >=150 min/week included living in a neighborhood with high perception of cohesion/safety versus low, living in walkable areas versus car-dependent, and living in an area with a low-moderate median income versus the lowest. Middle aged and older adults were more likely to walk >=150 min/week in a walkable, perceived safe/cohesive neighborhood. Identifying neighborhood factors associated with promoting walking among this population can enable stakeholders (e.g., researchers, planners, and policy makers) to direct interventions focusing on the built environment. PMID- 26994990 TI - Agreement of infrared temporal artery thermometry with other thermometry methods in adults: systematic review. AB - AIMS AND OBJECTIVES: To critically review and synthesise the evidence on the agreement of temporal artery thermometry with invasive and noninvasive thermometry methods in hospitalised adults. BACKGROUND: Noninvasive thermometry methods aim at combining patient comfort and ease of use with satisfactory accuracy of temperature measurements. Infrared temporal artery thermometry is based on the detection of heat radiated from this artery in the forehead and temporal region. DESIGN: Systematic literature review. METHODS: A literature search was conducted in Pubmed, CINAHL, Cochrane Library, Web of Science and Embase. Data were extracted from twenty method-comparison studies published between 2002-2015. Methodological quality of selected studies was evaluated. RESULTS: Temperature measurements of temporal artery were compared with pulmonary artery, urinary bladder, oesophageal or nasopharyngeal ones in eight studies for the whole temperature range. Accuracy and precision of temporal artery thermometry exceeded recommended levels of 0.3 degrees C in three and six studies respectively. Likewise, in nine studies that compared temporal artery temperature measurements with oral and ear-based ones, satisfactory agreement and variability was reported in five and none of them respectively. With regard to fever and hypothermia, although specificity of temporal artery thermometers for detecting these disorders was satisfactory, their sensitivity was low. CONCLUSIONS: Existing evidence does not support that temporal artery thermometry can replace common invasive and noninvasive thermometry methods in adult patients. RELEVANCE TO CLINICAL PRACTICE: Health care professionals are recommended to avoid the use of infrared temporal artery temporal artery thermometry in adults, or be cautious about the accuracy and precision of its readings, until improved devices are developed. PMID- 26994991 TI - Waiting for a kidney transplant: the experience of patients with end-stage renal disease in South Korea. AB - AIMS AND OBJECTIVES: To explore the experiences of Korean patients with end-stage renal disease awaiting kidney transplantation. BACKGROUND: The need for kidney transplantation has increased worldwide, while the number of kidney donors has not increased commensurately. This mismatch is a serious issue in South Korea. Prolonged waits for transplantation may cause physical and psychosocial issues and lead to poor outcomes. Nevertheless, the experience of waiting for kidney transplantation in South Korea has never been explored in depth. DESIGN: A qualitative descriptive design was used. METHODS: The participants were eight patients diagnosed with end-stage renal disease on the waiting list for kidney transplantation in South Korea. Data were collected through individual in-depth interviews. All conversations during interviews were recorded and transcribed verbatim. Transcribed data were analysed using conventional content analysis. RESULTS: The experience of waiting for kidney transplantation consisted of six categories: (1) the light at the end of the tunnel, (2) being on call without any promise, (3) a tough tug of war between excitement and frustration, (4) doubts in the complexity, (5) A companion on the hard journey and (6) getting ready for D day. CONCLUSIONS: Kidney transplantation candidates experience psychosocial difficulties and concerns while waiting for long periods of time without any assurance of resolution. Systematic education and psychosocial support from health care professionals and family members help patients get through what they describe as a difficult journey. Comprehensive management programs for kidney transplantation candidates are needed. RELEVANCE TO CLINICAL PRACTICE: Health care professionals need to recognise the psychosocial concerns of patients awaiting kidney transplantation. Clinicians should provide patients with information and support throughout the waiting period. PMID- 26994992 TI - Abdominal wall muscle elasticity and abdomen local stiffness on healthy volunteers during various physiological activities. AB - The performance of hernia treatment could benefit from more extensive knowledge of the mechanical behavior of the abdominal wall in a healthy state. To supply this knowledge, the antero-lateral abdominal wall was characterized in vivo on 11 healthy volunteers during 4 activities: rest, pullback loading, abdominal breathing and the "Valsalva maneuver". The elasticity of the abdominal muscles (rectus abdominis, obliquus externus, obliquus internus and transversus abdominis) was assessed using ultrasound shear wave elastography. In addition, the abdomen was subjected to a low external load at three locations: on the midline (linea alba), on the rectus abdominis region and on lateral muscles region in order to evaluate the local stiffness of the abdomen, at rest and during "Valsalva maneuver". The results showed that the "Valsalva maneuver" leads to a statistically significant increase of the muscle shear modulus compared to the other activities. This study also showed that the local stiffness of the abdomen was related to the activity. At rest, a significant difference has been observed between the anterior (0.5N/mm) and the lateral abdomen locations (1N/mm). Then, during the Valsalva maneuver, the local stiffness values were similar for all locations (ranging from 1.6 to 2.2N/mm). This work focuses on the in vivo characterization of the mechanical response of the human abdominal wall and abdomen during several activities. In the future, this protocol could be helpful for investigation on herniated patients. PMID- 26994993 TI - Anemia in type 2 diabetic patients and correlation with kidney function in a tertiary care sub-Saharan African hospital: a cross-sectional study. AB - BACKGROUND: Anemia is common in diabetic patients and increases morbidity and mortality, but its burden has been less well characterized in sub-Saharan Africans. We determined the prevalence of anemia and investigated the related factors, with a particular focus on the role of declining renal function, in type 2 diabetic patients attending a tertiary health care institution in Cameroon. METHODS: Hemoglobin (Hb) levels were measured in a consecutive sample of patients with type 2 diabetes, who reported for annual review at the outpatient section of the Douala General Hospital in 2013. Patients were classified as anemic according to the World Health Organisation criteria (Hb < 12 g/dl for females and Hb < 13 g/dl for males). Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease Study Group formula. Determinants of Hb concentration and anemia were investigated using multivariable logistic regressions. RESULTS: A total of 636 patients were examined including 263 (prevalence rate 41.4 %) who had anemia. The prevalence of anemia increased significantly with deteriorating kidney function, although up to 31.9 % of patients with normal kidney function had anemia. Compared with their non-anemic counterparts, anemic diabetic patients were older, had longer duration of diabetes, lower eGFR, higher prevalence of proteinuria and diabetic retinopathy (all p < 0.05). In multivariable logistic regressions, eGFR (p = 0.001) and presence of retinopathy (p = 0.023) were the independent determinants of prevalent anemia. CONCLUSIONS: The prevalence of anemia is high in type 2 diabetic patients attending referral institutions in Cameroon, including among those without chronic kidney disease. Routine screening for anemia in all diabetic patients may aid early identification and correction as appropriate. PMID- 26994994 TI - DNA strand break dependence on Tris and arginine scavenger concentrations under ultra-soft X-ray irradiation: the contribution of secondary arginine radicals. AB - In this study, we used a bench-top cold-cathode ultra-soft X-ray (USX) generator to expose aqueous DNA plasmid solutions to low-LET radiation under various scavenging conditions. Single- and double-strand breaks were assessed using classic gel electrophoresis quantification of linear, circular and supercoiled plasmid DNA topologies. With their very low penetration range in water, USX can only interact with matter up to short distances, of the order of 50 MUm. We validated a stirring procedure which makes it possible to expose 100 uL of aqueous samples (2 mm thick). The scavenging of OH radicals by Tris buffer was studied at ambient temperature under aerobic conditions and compared to data gathered in the literature. A very good agreement was found with the rare data dealing with DNA plasmid exposed to Al Kalpha photons at low temperature (T <= 277 K), which therefore validated the experimental procedure. The yields for DNA single-strand breaks determined during this study enabled the ratio of indirect to direct effects to be determined at 96.2%, in good agreement with the value of 97.7% stemming from a study based on gamma-ray irradiation of frozen solutions of plasmid DNA. Then, arginine was used both to create a "biological-like" chemical environment around the DNA plasmids and as an OH radical scavenger, in vitro. Although arginine has a greater scavenging (protecting) power than Tris, surprisingly, it led to higher rates of strand breakage. Based on the specific binding modes of arginine to DNA, we suggest that the side effects observed are due to the presence of arginine near to, but also inside, the DNA double helix. PMID- 26994995 TI - An evaluation of novel real-time technology as a tool for measurement of radiobiological and radiation-induced bystander effects. AB - The xCELLigence real-time cell impedance system uses a non-invasive and label free method to create a cell index that is a composite measure of cell proliferation. The aim of this study was to evaluate xCELLigence against clonogenic assay (gold standard) for measuring radiobiological effects and radiation-induced bystander effects (RIBE). A radiobiological study was conducted by irradiating EMT6.5, 4T1.2 and NMUMG cell lines with different radiation doses, while a RIBE study was done using transfer of conditioned media (CM) harvested from donor to the same type of recipient cell (EMT6.5, 4T1.2, NMUMG, HACAT and SW48). CM was harvested using two protocols which differed in the dose chosen and the exposure to the recipient cells. Results showed that xCELLigence measured a radiobiological effect which correlated with the clonogenic assay. For the RIBE study, no statistically significant differences were observed between xCELLigence or clonogenic survival in control or recipient cells incubated with CM in protocol one. However, there was a significant increase in cell index slope using CM from EMT-6.5 cells irradiated at 7.5 Gy compared with the control group under the second protocol. No other evidence of RIBE was detected by either xCELLigence or clonogenic assay. In conclusion, xCELLigence methods can measure radiobiological effects and the results correlate with clonogenic assay. We observed a lack of RIBE in all tested cell lines with the clonogenic assay; however, we observed a RIBE effect in EMT6.5 cells under one particular protocol that showed RIBE is cell type dependent, is not universally observed and can be detected in different assays. PMID- 26994996 TI - Risk of lower extremity arterial disease in a cohort of workers occupationally exposed to ionizing radiation over a prolonged period. AB - In this study the incidence risk of lower extremity arterial disease (LEAD; international classification of diseases version 9 code 440.2) was assessed in a cohort of workers occupationally exposed to radiation over a prolonged period. The study cohort includes 22,377 workers of the Mayak Production Association (25% of whom are females) first employed at one of the main facilities in 1948-1982 and followed up to the end of 2008. Dose estimates used in the study are provided by Mayak Worker Dosimetry System 2008. The mean total dose from external gamma rays is 0.54 Gy for males and 0.44 Gy for females. The mean absorbed liver dose from internal alpha-radiation due to incorporated plutonium is 0.23 Gy in males and 0.44 Gy in females. Relative risks and excess relative risks per unit dose (ERR/Gy) are calculated based on maximum likelihood. A total of 943 cases of LEAD are registered in the study cohort during the follow-up of 512,801 person-years. A significant association of LEAD incidence with total dose from external gamma rays (based on a linear model) was revealed, and the ERR/Gy is 0.27 (95% confidence interval (CI) 0.11; 0.48). It turned out that a linear-exponential model provides a better fit of the data (?AIC = 9.957). Inclusion of an adjustment for internal alpha-radiation dose resulted in the reduction of the ERR/Gy to 0.19 (95% CI 0.05; 0.39), but the risk remains significant. No association of LEAD incidence with dose from internal alpha-radiation was found in the study worker cohort. It is concluded that this study provides evidence for an association of LEAD incidence with dose from external gamma-rays taking non radiation factors into account. PMID- 26994997 TI - CLE peptide signaling and nitrogen interactions in plant root development. AB - The CLAVATA signaling pathway is essential for the regulation of meristem activities in plants. This signaling pathway consists of small signaling peptides of the CLE family interacting with CLAVATA1 and leucine-rich repeat receptor-like kinases (LRR-RLKs). The peptide-receptor relationships determine the specificities of CLE-dependent signals controlling stem cell fate and differentiation that are critical for the establishment and maintenance of shoot and root apical meristems. Plants root systems are highly organized into three dimensional structures for successful anchoring and uptake of water and mineral nutrients from the soil environment. Recent studies have provided evidence that CLE peptides and CLAVATA signaling pathways play pivotal roles in the regulation of lateral root development and systemic autoregulation of nodulation (AON) integrated with nitrogen (N) signaling mechanisms. Integrations of CLE and N signaling pathways through shoot-root vascular connections suggest that N demand modulates morphological control mechanisms and optimize N uptake as well as symbiotic N fixation in roots. PMID- 26994998 TI - Methicillin-susceptible Staphylococcus aureus skin infections among military conscripts undergoing basic training in Bangkok, Thailand, in 2014. AB - BACKGROUND: Skin and soft tissue infections are common among military conscripts undergoing close-contact training activities. On June 4, 2014, an outbreak of Staphylococcus aureus skin infection was reported among military conscripts undergoing basic training in Bangkok, Thailand. An investigation was performed to verify the outbreak and recommend future prevention and control strategies. CASE PRESENTATION: The outbreak resulted in a rate of infection of 19.2% and a fatality rate of 2.5% (one death). All were Thai men aged 21.2 +/- 1.0 years. Risk factors associated with infection were multiple erythematous papules and training in certain subunits. Randomly selected isolates were evaluated by pulsed field gel electrophoresis to confirm the clonal identity. CONCLUSIONS: This report confirms that S. aureus skin infection can be fatal. Our study highlights the role of military personnel in the early detection, prompt treatment, and containment of outbreaks of skin infection, as well as other health issues among conscripts. PMID- 26994999 TI - Hesperetin Suppresses Inflammatory Responses in Lipopolysaccharide-Induced RAW 264.7 Cells via the Inhibition of NF-kappaB and Activation of Nrf2/HO-1 Pathways. AB - Hesperetin (Hesp), a common flavanone glycoside, was extracted from the fruit peel of Citrus aurantium L. (Rutaceae). Hesp has been shown to possess various biological properties, including antioxidant, neuroprotective, and anti inflammatory properties. In this study, we investigated the protective effect of Hesp on inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our results indicated that Hesp treatment dramatically suppressed secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta; reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expression; inhibited NF-kappaB (p65) phosphorylation; and blocked IkappaBalpha phosphorylation and degradation. Further studies revealed Hesp markedly enhanced the heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which were involved with inducing Nrf2 nuclear translocation and decreasing Keap1 protein expression. Together, these results indicated that the anti-inflammatory effect of Hesp may be associated with NF-kappaB inhibition and Nrf2/HO-1 activation. PMID- 26995000 TI - How does a cadaver model work for testing ultrasound diagnostic capability for rheumatic-like tendon damage? AB - To establish whether a cadaver model can serve as an effective surrogate for the detection of tendon damage characteristic of rheumatoid arthritis (RA). In addition, we evaluated intraobserver and interobserver agreement in the grading of RA-like tendon tears shown by US, as well as the concordance between the US findings and the surgically induced lesions in the cadaver model. RA-like tendon damage was surgically induced in the tibialis anterior tendon (TAT) and tibialis posterior tendon (TPT) of ten ankle/foot fresh-frozen cadaveric specimens. Of the 20 tendons examined, six were randomly assigned a surgically induced partial tear; six a complete tear; and eight left undamaged. Three rheumatologists, experts in musculoskeletal US, assessed from 1 to 5 the quality of US imaging of the cadaveric models on a Likert scale. Tendons were then categorized as having either no damage, (0); partial tear, (1); or complete tear (2). All 20 tendons were blindly and independently evaluated twice, over two rounds, by each of the three observers. Overall, technical performance was satisfactory for all items in the two rounds (all values over 2.9 in a Likert scale 1-5). Intraobserver and interobserver agreement for US grading of tendon damage was good (mean kappa values 0.62 and 0.71, respectively), with greater reliability found in the TAT than the TPT. Concordance between US findings and experimental tendon lesions was acceptable (70-100 %), again greater for the TAT than for the TPT. A cadaver model with surgically created tendon damage can be useful in evaluating US metric properties of RA tendon lesions. PMID- 26995001 TI - Diarrhea-associated hemolytic uremic syndrome with severe neurological manifestations treated with IgG depletion through immunoadsorption. AB - BACKGROUND: Diarrhea-associated hemolytic uremic syndrome (HUS) is characterized by acute kidney injury with microangiopathic hemolytic anemia and thrombocytopenia with a diarrhea prodrome, typically caused by Shiga-like toxin producing Escherichia coli. Supportive management is generally recommended. CASE REPORT: A 58-year-old female with diarrhea-associated HUS developed delayed-onset severe neurological manifestations including coma, status epilepticus, and subcortical magnetic resonance imaging signal alterations. Rescue treatment with immunoglobulin (Ig)G depletion through immunoadsorption was followed by significant improvement in neurological and renal function. The patient recovered with only minimal sequelae. CONCLUSION: Delayed-onset neurological abnormalities may occur in diarrhea-associated HUS. Novel specific treatment options include IgG depletion through immunoadsorption. Severe clinical and imaging findings do not preclude a good outcome. PMID- 26995002 TI - Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizumab treatment. AB - BACKGROUND: Eculizumab is approved for atypical hemolytic uremic syndrome (aHUS). Guidelines discuss the importance of prompt treatment. We report a post hoc analysis investigating the effect of baseline factors, including patient characteristics and time from the latest aHUS manifestation to eculizumab initiation, on change from baseline in estimated glomerular filtration rate (eGFR) and other outcomes. METHODS: Data were pooled from four phase 2, open label, single-arm, prospective clinical studies of eculizumab for patients with aHUS. Multivariate regressions identified predictors of eGFR change from baseline. The proportion of patients achieving sustained eGFR increase (defined: >=15 ml/min/1.73 m2 for >=28 days) and platelet count normalization were evaluated 1 year post-treatment. Baseline characteristics and eGFR outcomes were summarized by time to treatment from last aHUS manifestation [<=7 days (n = 21) versus >7 days (n = 76)]. RESULTS: Baseline eGFR were similar between groups. Multivariate regression analysis demonstrated time from aHUS manifestation to eculizumab treatment, age, baseline lactate dehydrogenase (LDH) and baseline hemoglobin were independently predictive of eGFR change from baseline. Mean eGFR change from baseline at 1 year was significantly higher in patients treated in <=7 days than >7 days (57 vs. 23 ml/min/1.73 m2, p = 0.0098). After 1 year, 17/21 and 36/76 patients in the <=7 and >7 day groups, respectively, achieved a sustained increase in eGFR. Mean time to platelet count normalization was similar between groups. CONCLUSIONS: Younger age, higher baseline LDH and lower baseline hemoglobin were associated with greater eGFR improvements. Early eculizumab initiation led to improved renal recovery, demonstrating the importance of rapid diagnosis and treatment of patients with aHUS. PMID- 26995004 TI - Protective Effects of 7-Hydroxycoumarin on Dyslipidemia and Cardiac Hypertrophy in Isoproterenol-Induced Myocardial Infarction in Rats. AB - This study evaluates the protective effects of 7-hydroxycoumarin (7-HC) on dyslipidemia and cardiac hypertrophy in isoproterenol (ISO) induced myocardial infarction (MI) in rats. Rats were pre- and co treated with 7-HC (16 mg/kg) daily for 8 days. ISO (100 mg/kg) was subcutaneously injected into rats on seventh and eighth days to induce MI. Increased activity/levels of serum creatine kinase-MB (CK-MB), troponin-T, plasma lipid peroxidation products, and altered levels of lipids in the serum and heart and serum lipoproteins were noted in ISO-induced rats. ISO-induced myocardial infarcted rats revealed increased hypertrophy (cardiac and left ventricular) and hepatic 3-hydroxyl 3-methylglutaryl-coenzyme-A reductase (HMG-CoA reductase) activity. Pre and cotreatment with 7-HC revealed significant protective effects on all the biochemical parameters evaluated. The in vitro study demonstrated its free radical scavenging property. Thus, 7-HC protects ISO-induced MI in rats by its free radical scavenging and antihyperlipidaemic and antihypertrophic properties. PMID- 26995003 TI - Renal resistive index by transesophageal and transparietal echo-doppler imaging for the prediction of acute kidney injury in patients undergoing major heart surgery. AB - BACKGROUND: Acute kidney injury (AKI) following major heart surgery (MHS) is associated with early decrease in renal blood flow and worsened prognosis. Doppler-derived renal resistive index (RRI), which reflects renal vascular resistance, may predict the development of AKI in patients undergoing MHS. METHODS: We studied 60 consecutive patients (mean age 69.5 years, range 30-88, 41 males) undergoing MHS. We measured RRI, both at the renal sinus and intraparenchymally, by transesophageal echo-Doppler ultrasound (TE-EDus) at anesthesia induction and at the end of surgery in all patients. Additionally, we measured RRI by external transparietal echo-Doppler ultrasound (TP-EDus) at the following time points: anesthesia induction, end of surgery, 4 and 24 h from cardiopulmonary bypass (CPB) start. We also measured serum neutrophil gelatinase associated lipocalin (NGAL) at the same time points. RESULTS: AKI [serum creatinine (sCr) increase >=0.3 mg/dl vs. baseline within 72 h] developed in 23/60 (38.3 %) patients, with two requiring dialysis. Systemic hemodynamic parameters were similar in the patients who developed AKI (AKI+) and in those who did not (AKI-). Intraparenchymal RRI at end-surgery was significantly higher in AKI+ compared to AKI- patients, both at TE-EDus and TP-EDus (TE-EDus mean difference, p = 0.004; TP-EDus mean difference, p = 0.013; difference between TE EDus and TP-EDus results, p = 0.066), although the predictive performance was limited with both methods (area under the curve [AUC] of the receiver-operator characteristics: 0.71 and 0.70 for TE-EDus and TP-EDus, respectively). Serum NGAL values were higher in AKI + than in AKI- patients (anesthesia induction, p = 0.037; end-surgery, p = 0.007; 4 h from CPB start, p = 0.093; 24 h from CPB start, p = 0.024. However, combining RRI with serum NGAL at end-surgery did not provide a clear-cut advantage in predicting AKI. CONCLUSIONS: In patients undergoing MHS, increased echo-Doppler ultrasound-derived RRI at end-surgery is significantly associated with the risk of AKI, but has limited practical utility for identifying the patients who will develop AKI. PMID- 26995005 TI - Illness perceptions are associated with mortality among 1552 colorectal cancer survivors: a study from the population-based PROFILES registry. AB - PURPOSE: Cancer survivors construct perceptions of illness as a (mal)adaptive mechanism. These perceptions motivate/drive subsequent self-management behaviors toward symptoms and treatment that influence health outcomes. Negative illness perceptions have been associated with increased mortality in other chronically ill groups. However, this association is under-researched in cancer survivors. We aimed to explore the association between illness perceptions and mortality in stage I-III progression-free colorectal cancer (CRC) survivors. METHODS: We used data from the population-based Patient Reported Outcomes Following Initial treatment and Long Term Evaluation of Survivorship (PROFILES) registry of two CRC survivorship studies conducted in 2009 and 2010. We accessed clinical data from the Netherlands Cancer Registry, and mortality data from municipal personal records database. Follow-up was until 31 December 2014. Survivors (n = 1552) completed the Brief Illness Perception Questionnaire. Cox proportional hazard models estimated the association between illness perceptions and mortality. RESULTS: Negative illness perceptions on consequences (adjusted hazard ratio (HRadj) 1.60, 95 % confidence interval (CI) 1.14-2.25) and emotion (HRadj 1.65, 95 % CI 1.18-2.31) were associated with higher mortality, after adjusting for demographic, clinical, and lifestyle factors. Smoking and inadequate physical activity were independently associated with mortality for all Brief Illness Perception Questionnaire (BIPQ) dimensions. CONCLUSIONS: Survivors' perceptions of their illness are important as these perceptions may influence health outcomes during survivorship period. Clinical practice needs to identify and address maladaptive illness perceptions to support more adaptive self-management behaviors and enhance survivorship. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors may benefit from interventions that address potentially maladaptive perceptions and encourage more adaptive self-management behaviors. PMID- 26995006 TI - Gender differences in associations between cancer-related problems and relationship dissolution among cancer survivors. AB - PURPOSE: Research suggests that a cancer diagnosis predicts marital dissolution more strongly for women survivors than men, but there is a paucity of research on potential processes underlying this vulnerability. The present cross-sectional study examined whether specific cancer-related problems were associated with the odds of relationship breakup following diagnosis and whether these relationships differed between male and female cancer survivors. METHODS: A national cross sectional quality of life study assessed self-reported cancer-related problems and relationship change among survivors who were either 2, 6, or 10 years post diagnosis (n = 6099). RESULTS: Bivariate analyses indicated that cancer-related problems (e.g., emotional distress) were greater for divorced/separated survivors compared to those with intact relationships and were greater for women versus men. Logistic regressions indicated that for both male and female survivors, lower income, younger age, and longer time since diagnosis were associated with greater odds of divorce or separation after diagnosis (ORs > 2.14, p < .01). For women only, greater emotional distress (OR = 1.14, p < 0.01) and employment and financial problems (OR = 1.23, p < 0.0001) were associated with greater odds of post-diagnosis divorce or separation. For men only, fear of cancer recurrence was associated with greater odds of divorce or separation (OR = 1.32, p < 0.001). CONCLUSION: Female and male survivors differed in the extent to which emotional or financial/employment problems attributed to the cancer diagnosis were associated with the likelihood of reporting relationship dissolution. IMPLICATIONS FOR CANCER SURVIVORS: Although directions of causality could not be ascertained, results suggest the possibility that helping male and female cancer survivors cope with specific cancer-related problems may benefit the quality and stability of their relationships with significant others following diagnosis. PMID- 26995007 TI - The impact of stage of chronic kidney disease on the outcomes of diabetics with acute myocardial infarction treated with percutaneous coronary intervention. AB - BACKGROUND: Patients with diabetes mellitus (DM) or chronic kidney disease (CKD) have a high risk of acute myocardial infarction and recurrent cardiovascular events. According to the previous studies, the combination of the two conditions may have a synergistic impact on prognosis. The aim of this study was to assess the impact of stage of CKD on the outcomes of patients with DM and ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). METHODS: Study population consisted of 946 consecutive patients with STEMI who underwent PCI from January 2009 to December 2012 and were followed up until the end of 2013. The all-cause mortality during this period was evaluated in relation to DM and severe or moderate reduction in glomerular filtration rate (GFR categories G4-5, or G3; KDIGO classification). Cox regression analysis adjusted for possible confounding factors was used in statistics. RESULTS: Out of the study population (mean age 63 years, 69.6 % males), 217 (22.9 %) patients had DM. Of them, 10.6 % were in GFR category G4-5 and 32.7 % in G3. The in-hospital mortality rates in patients with DM were 34.8 % for G4-5, 18.3 % for G3, and 4.1 % in G1-2 groups. The all-cause mortality at the end of the follow-up period for diabetics within G4-5 was 2.27 -times higher compared to mortality of diabetics in G1-2 (p = 0.047, Cox regression analysis), and there was a trend toward higher mortality for G3 versus G1-2 (HR 1.64, p = 0.12). CONCLUSION: Severe chronic kidney disease (GFR category 4-5) was significantly associated with all-cause mortality of diabetics with STEMI treated with PCI; the association with severe CKD was stronger compared to moderate CKD. PMID- 26995008 TI - Chronic kidney disease as an important risk factor for tumor recurrences, progression and overall survival in primary non-muscle-invasive bladder cancer. AB - PURPOSE: To evaluate the impact of chronic kidney disease (CKD) on oncologic outcomes among non-muscle-invasive bladder cancer (NMIBC) patients who underwent transurethral resection of bladder cancer. METHODS: We followed up the medical data of 158 newly diagnosed NMIBC patients enrolled in this study for more than 4 years. The ten putative risk factors included patient age, gender, white blood cells, neutrophil to lymphocyte ratio, tumor count, size, grade, stage, CKD (estimated glomerular filtration rate, eGFR < 60) and histological differentiation. RESULTS: Total recurrent bladder and upper urinary tract (UUT) tumors were observed in 51 patients (32 %) and 5 patients (3 %), respectively. Cancer progression to the high pT(>=pT2) stage was found in 9 patients (6 %). Cancer-specific and overall survival rates were 91 % (144/158 patients) and 78 % (123/158 patients), respectively. In univariate analysis, significant predictive determinants were tumor count, size, grade, stage, CKD and squamous differentiation for bladder tumor recurrence; CKD and squamous differentiation for UUT tumor recurrence; and tumor count, grade, stage and CKD for cancer progression. On the other hand, old age (>70 years), high grade, T1 stage, and CKD were poor prognostic factors for overall survival. In multivariate analysis, CKD was an independent risk factor for bladder/UUT tumor recurrences and the overall survival rate. CONCLUSIONS: NMIBC patients with CKD had worse prognosis and higher tumor recurrence and progression rates than other patients. These patients should be intensively monitored at upper and lower urinary tracts and be aggressively treated for comorbidities of CKD. PMID- 26995009 TI - A Novel Mutation in a Patient with Hyperparathyroidism-Jaw Tumour Syndrome. AB - Hyperparathyroidism-jaw tumour syndrome (HPT-JT) is a rare variant of familial hyperparathyroidism, characterized by primary hyperparathyroidism (PHPT) due to one or multiple parathyroid adenomas, and benign tumours of the mandible and maxilla. It has an autosomal dominant pattern of inheritance, and is associated with mutations that deactivate the cell division cycle protein 73 homolog (CDC73) gene, also known as hyperparathyroidism 2 (HRPT2), located on the long arm of chromosome 1, that encodes for the tumour suppressor protein parafibromin. In the majority of cases, PHPT is the presenting symptom, but up to 30 % of HPT-JT cases initially present with an ossifying fibroma of the maxillofacial bones. HPT-JT may result in severe hypercalcemia-related complications and an elevated risk of parathyroid carcinoma. For this reason, early identification of the disease is important. We present the case of a 23-year-old woman who was found to have jaw tumours and was later diagnosed with PHPT. Genetic analysis revealed a novel mutation in exon 1 of CDC73. This report contributes to the understanding of the genetics of this rare syndrome. It also highlights the fact that HPT-JT should be considered and CDC73 mutation analysis should be performed in cases of early onset PHPT associated with ossifying fibromas of the jaw. PMID- 26995010 TI - Zinc oxide-copper oxide nanoplates composite as coating for solid phase microextraction combined with high performance liquid chromatography-UV detection for trace analysis of chlorophenols in water and tomato juice samples. AB - In the present research, the ZnO-CuO nanoplate composite (ZCNC), solid-phase microextraction (SPME) fiber coating, was prepared and its extraction capability for certain chlorophenols (CPs) was studied through directly sampling the typical CPs mixed standard solution of 4-chlorophenol, 2,3-dichlorophenol, 2,5 dichlorophenol, and 2,4,6-trichlorophenol with high performance liquid chromatography. ZCNC thickness was in the range of 50-65 nm. The effective variables on ZCNC-SPME extraction efficiency were extraction time, salt percentage, and desorption time. Accordingly, a multivariate strategy was applied based on an experimental design by using central composite design for optimizing the significant factors affecting the extraction efficiency. The detection limit and relative standard deviation (RSD) (n = 6), that include repeatability and reproducibility as the target analytes, were in the range of 0.5-5 ng ml(-1) and 5.1-14 % of standard solutions at 50 ng ml(-1) concentration of CPs, respectively. The developed technique is believed to be successfully applicable to preconcentration and determination of target analytes in environmental water and tomato juice samples. Graphical Abstract Application of zinc oxide-copper oxide nanoplates composite for extraction of chlorophenols in water and tomato juice samples and optimizing condition by experimental design method. PMID- 26995011 TI - Evaluation of a Portable Haemoglobin Metre Performance in Children with Sickle Cell Disease and Implications for Healthcare in Resource-poor Settings. AB - BACKGROUND: Sub-Saharan Africa has the largest burden and worst outcome of sickle cell disease (SCD). This gloomy outlook has been attributed to the lack of use of simple and cost-effective measures for diagnosis and treatment of the disease. Although haematology analysers are the gold standard for accurate measurement of haemoglobin (Hb) concentration, they are often out of reach of most health facilities in resource-poor settings, thus creating a care gap. We conducted this study to examine the agreement between a point-of-care device and haematology analyser for determining the Hb concentration in children with SCD and its usefulness in resource-poor settings. METHODS: Ethylenediaminetetraacetic acid blood samples collected from participants were processed to estimate their Hb concentration using two devices (Sysmex KX21N haematology analyser and portable mission Hb device). The agreement between the two sets of measurements was assessed by the Bland and Altman method. RESULTS: The intraclass and concordance correlation coefficients were 0.854 and 0.936, respectively. Sensitivity and specificity were 84.2% and 98.6%, respectively. The positive and negative predictive values were 94.1% and 96.0%, respectively. The Bland and Altman's limit of agreement was -2.3 to 1.6 and the mean difference was -0.34 with non significant variability between the two measurements (p = 0.949). CONCLUSION: Hb concentration determined by the portable testing system is comparable with that determined by the haematology analyser. We recommend its use as a point-of care device for determining Hb concentration of SCD children in resource-poor settings where haematology analysers are not available. PMID- 26995012 TI - Assessment of Vitamin D Status and Response to Vitamin D3 in Obese and Non-Obese Iranian Children. AB - BACKGROUND: Obesity seems to be a critical issue nowadays because of its high prevalence and its adverse effects on health. There is some evidence indicating the relationship between obesity and lower serum 25-hydroxyvitamin D [25(OH)D] concentration. The aim of the present study was to examine serum 25(OH)D status of obese and non-obese Iranian children and compare their therapeutic response with identical oral vitamin D3 treatment. METHODS: In a non-randomized clinical trial, serum 25(OH)D level of 45 obese and 45 non-obese Iranian children aged 2 14 years was measured. Those with serum 25(OH)D status <30 ng/ml (73 cases) were treated with one pearl of vitamin D3 (50 000 International Units) once a week for 6 weeks. Serum vitamin D was measured once more 2 weeks after treatment. RESULTS: The frequency of hypovitaminosis D was 43/45 (95.6%) in obese and 30/45 (66.7%) in non-obese children at baseline (p < 0.001). After treatment of 73 cases (43 obese, 30 non-obese), the above percentages were decreased to 24/43 (55.8%) and 1/30 (3.3%), respectively (p < 0.001). CONCLUSION: Our study demonstrated a high frequency of vitamin D deficiency among Iranian children, particularly the obese ones. Moreover, low therapeutic response in the obese group is witnessed. PMID- 26995013 TI - In vitro and in vivo evaluations of the P-glycoprotein-mediated efflux of dibenzoylhydrazines. AB - P-glycoprotein (P-gp) is a member of the ATP-binding cassette transporter family. It actively transports a wide variety of compounds out of cells to protect humans from xenobiotics. Thus, determining whether chemicals are substrates and/or inhibitors of P-gp is important in risk assessments of pharmacokinetic interactions among chemicals because P-gp-mediated transport processes play a significant role in their absorption and disposition. We previously reported that dibenzoylhydrazines (DBHs) such as tebufenozide and methoxyfenozide (agrochemicals) stimulated P-gp ATPase activity. However, it currently remains unclear whether these derivatives are transport substrates of P-gp and inhibit transport of other chemicals by P-gp. In the present study, in order to evaluate the interactions of DBHs with other chemicals in humans, we determined whether DBHs are P-gp transport substrates using both the in vitro bidirectional transport assay and the in vivo study of rats. In the in vivo study, we investigated the influence of P-gp inhibitors on the brain to plasma ratio of methoxyfenozide in rats. We also examined the inhibitory effects of DBHs on quinidine (a P-gp substrate) transport by P-gp in order to ascertain whether these derivatives are inhibitors of P-gp. Based on the results, DBHs were concluded to be weak P-gp transport substrates and moderate P-gp inhibitors. However, the risk of DBHs caused by interaction with other chemicals including drugs was considered to be low by considering the DBHs' potential as the substrates and inhibitors of P-gp as well as their plasma concentrations as long as DBHs are properly used. PMID- 26995014 TI - A Three-Enzyme Pathway with an Optimised Geometric Arrangement to Facilitate Substrate Transfer. AB - Cascade reactions drive and regulate a variety of metabolic activities. Efficient coupling of substrate transport between enzymes is important for overall pathway activity and also controls the depletion of intermediate molecules that drive the reaction forward. Here, we assembled a three-enzyme pathway on a series of DNA nanoscaffolds to investigate the dependence of their activities on spatial arrangement. Unlike previous studies, the overall activity of the three-enzyme pathway relied less on inter-enzyme distance and more on the geometric patterns that arranged them within a relatively small range of 10-30 nm. Pathway intermediate detection demonstrated that the assembled enzyme systems quickly depleted the intermediate molecules through efficient reaction coupling. PMID- 26995015 TI - Non-melanoma skin cancer by solar UV: the neglected occupational threat. PMID- 26995016 TI - Skin cancer risk in outdoor workers: a European multicenter case-control study. AB - BACKGROUND: Exposure to ultraviolet radiation (UVR) is the most important external risk factor for skin cancer. Outdoor workers, who are exposed to high ambient UVR levels are at increased risk. OBJECTIVE: To compare outdoor with indoor workers in terms of: (i) skin cancer risk factors, and (ii) risk of developing skin cancer. METHODS: Using descriptive methods and a large multicenter European case-control study, we compared risk factor patterns between outdoor (N = 1416) and indoor workers (N = 1863). Risk of developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma and actinic keratosis (AK) were analysed by type of work using multivariate logistic regression models, for three categories of work: indoor; farming/construction; other outdoor work. RESULTS: Although skin phototype was equally distributed by type of work, significantly less outdoor than indoor workers used sunscreen in their own country (44.3% vs. 60.2%), but had more outdoor hobbies (66.2% vs. 58.2%). Outdoor workers had lower educational levels, and felt less confident in understanding medical information and filling medical forms (all P < 0.001). Outdoor workers had more signs of photodamage (78.1% vs. 65.5%) and among the skin cancer patients, 37.7% of outdoor workers vs. 28.6% of indoor workers had >=2 skin cancers diagnosed during their lifetime. Multivariate logistic regression models showed significantly increased risk of outdoor vs. indoor work for AK (ORother outdoor = 1.55, ORfarming/construction = 2.58), SCC (ORother outdoor = 1.32, ORfarming/construction = 2.77) and BCC (ORother outdoor = 1.53, ORfarming/construction = 1.83). No significant associations were found for melanoma. The risk of all types of skin cancer and AK was significantly increased for workers with >=5 years of outdoor work. CONCLUSIONS: Outdoor workers had more risk behaviour with similar constitutional skin cancer risk factors: more UV exposure (both occupational and leisure) and less sunscreen use and lower health literacy. This results in higher exposure, more photodamage and an increased risk of developing AK, BCC and SCC. PMID- 26995017 TI - The experience of a tertiary referral centre in Romania on basal cell carcinomas in outdoor workers: why to assess? AB - BACKGROUND: Published epidemiological literature indicates that outdoor workers are at significantly increased risk for developing basal cell carcinomas. OBJECTIVES: The main objective is to identify basal cell carcinoma features in patients with prolonged occupational exposure to UV radiation and compare them to basal cell carcinoma in patients with no occupational exposure to UV radiation. METHODS: Data regarding age, gender, living area, occupation, number of lesions, involved anatomic site and histologic subtype of tumor were collected from the charts of 321 patients diagnosed with basal cell carcinoma in our department between 01.01.2013-31.12.2014. We divided the patient population in which the occupation was accurately identified in two study groups: occupations with UV exposure (OW), and non-UV exposed occupations (IW) and we compared the clinical and histologic features of the lesions in the two groups. RESULTS: The most affected area in both groups was the facial "mask area". The cheek was second most affected area in exposed group whereas the scalp area was the second most affected in the non-exposed group. The nodular pattern is the most numerous in both groups (30 lesions in OW group and 15 lesions in the IW group with a mean number of lesions of 1.57+/-0.90 and 1.27+/-0.46, respectively) with the mixed type being the second most frequent type for both groups. However, for the OW group the mixed type with an aggressive component was the second most frequent one, while in the non-exposed group, the mixed type with non-aggressive components was the second most frequent, the difference being statistically significant. A multinomial logistic regression analysis was conducted to predict the presence of histopathologically aggressive lesions using gender, age, exposure and anatomical site out of which UV exposure and 3 main anatomical sites (mask zone, cheek and torso) were selected in the final analysis. The probability of the model chi-square (9.430), p = .05, supports a relationship between the dependent variable and the independent variables. CONCLUSION: Our data suggest that in Romania patients diagnosed with basal cell carcinoma, occupationally exposed to UV radiation, develop more frequently lesions on the "mask area" of the face; furthermore, prediction of the histo-pathologically aggressive lesions may be supported by the presence of occupational UV exposure and anatomical site (mask zone, cheek and torso) involved.Also, these patients may be at a higher risk to develop more aggressive histologic subtype BCCs. Although limited by a number of factors, especially the small number of subjects, these data suggest the necessity of conducting both retrospective and prospective studies on clinical and histological types of BCCs evolving in patients working outdoor along with identifying additional risk factors. PMID- 26995019 TI - Questionnaire-based evaluation of occupational and non-occupational solar radiation exposure in a sample of Italian patients treated for actinic keratosis and other non-melanoma skin cancers. AB - BACKGROUND: An adequate evaluation of the ultraviolet (UV) cumulative exposure is a major problem in epidemiological studies on chronic skin damage. Questionnaires may be applied as useful tools. OBJECTIVE: We developed an original questionnaire to evaluate individual cumulative exposure to solar radiation (SR) in patients affected by actinic keratosis (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHOD: The questionnaire, considering both working and leisure exposure, was applied to evaluate the whole life history of solar UV radiation exposure in a group of patients of the Dermatologic Clinic of UNIMORE. RESULTS: In outdoor workers (OW), the co-presence of AK/in situ SCC and invasive non melanoma skin cancers (NMSCs) was increased compared to indoor workers (IW), as was the frequency of multiple skin lesions. The prevalence of skin lesions of the face was significantly higher in OW. Work 'sometimes' or 'often' in the shades was associated with an absence of skin lesions on the shoulders and neck, while workers adopting 'sometimes' or 'often' a downward bent position were more likely to develop lesions on the top of the head. Considering leisure activities, the use of tanning beds was associated to the presence of skin lesions on the shoulders, neck and chest. Considering vacation periods, subjects spending at least 2 h outdoor in the period 11 am to 1 pm presented earlier diagnoses of skin cancers. CONCLUSION: Results of the original questionnaire developed are coherent with current knowledge and confirm the important role of UV exposure, both occupational and recreational, in the development of AK and NMSCs. Data support the hypothesis that this questionnaire can be applied as useful tool for the evaluation of cumulative UV exposure in future epidemiological studies. PMID- 26995018 TI - Farmers develop more aggressive histologic subtypes of basal cell carcinoma. Experience from a Tertiary Hospital in Northern Greece. AB - BACKGROUND: Ultraviolet radiation plays an important role in the pathogenesis of non-melanoma skin cancer. Outdoor workers, including farmers, experience higher exposure levels compared to the general population. Available literature data suggest that occupational ultraviolet exposure represents an independent risk factor for squamous cell carcinoma; whereas for basal cell carcinoma (BCC) this association still remains unclarified. OBJECTIVES: To analyse the epidemiological, clinical and histological data of patients diagnosed with BCC, and correlate them with outdoor occupation in farmers. METHODS: Individuals with histologically diagnosed BCCs, between September 2013 and September 2015, were included in the study. Their medical data, including epidemiological, clinical and histological characteristics, were recorded and analysed in conjunction with the occupation. Farmers were identified based on their specific public health insurance. RESULTS: Three hundred and forty patients, with 542 BCCs were included in the study. One hundred and twenty (35.3%) were farmers. Mean age of farmers was lower than non-farmers (66.0 +/- 9.1 years vs. 75 +/- 6.6 years, Mann-Whitney U-test, P < 0.001). Farmers had a sixfold higher probability for exhibiting photodamaged skin (OR = 6.02, 95% CI: 3.66-9.90, P < 0.001). Farmer workers were more likely to exhibit infiltrative or morpheaform BCC, but less likely to develop superficial BCC. CONCLUSION: Our results indicate a higher risk of earlier development of more aggressive histological subtypes of BCCs in farmers. Photodamage was also more common in this group. Primary and secondary prevention strategies focusing on outdoor workers, including farmers, are mandatory. PMID- 26995020 TI - An approximation of occupational lifetime UVR exposure: algorithm for retrospective assessment and current measurements. AB - BACKGROUND: Since non-melanoma skin cancer (NMSC) has been adopted as an occupational disease in Germany, in any single suspected case a retrospective estimation of the outdoor workers' occupational UVR exposure is mandatory. OBJECTIVE: The aim of this study was to introduce the recent German standard procedure as a mathematical algorithm for retrospectively estimating individual occupational UVR lifetime exposure. In addition, to present results of exemplary on-the-job UVR dosimetry measurements on outdoor workers during their various occupational activities. These dosimetry data form the basis of the mathematical model for UVR exposure estimation. METHODS: On-the-job personal dosimetry in various outdoor professions was conducted using the GENESIS-UV measurement system for individual UVA/UVB exposure assessment. The algorithm is derived from the results of these pars pro toto exemplary dosimetric measurements. For retrospective UVR lifetime estimation in suspected cases, a standardized patient interview serves as input and delivers all necessary information for using the algorithm. With defined factors, an individual adjustment is achieved. RESULTS: Inserting the data derived from the patient interview, the algorithm shows to be feasible to calculate the lifetime UVR exposure retrospectively. As an example, an assessment for a 67-year-old agricultural teacher with three distinct occupational UVR exposure episodes is calculated. CONCLUSION: The presented algorithm has proven to facilitate the anamnestic procedure to estimate the lifetime UVR dose of exposed outdoor workers. With a recently developed computer based tool, standardized interviews of suspected workers with NMSC become simple. UVR dose as well as matching of requirements for recognition as an occupational disease in an individual worker are calculated automatically. Furthermore, with ongoing on-the-job measurements, a database is created to continuously adjust the algorithm's reference values for the various UVR-exposed occupations. In addition, a job exposure matrix UVA/UVB is created as a pivotal tool for improved health and safety of outdoor workplaces and prevention of occupational actinic damage to the skin. PMID- 26995021 TI - Knowledge of outdoor workers on the effects of natural UV radiation and methods of protection against exposure. AB - The most important but influenceable risk factor in the development of skin cancer is the unprotected exposure to solar ultraviolet (UV) radiation. In order to assure adequate and effective protection against UV exposure, a level of knowledge about solar radiation and its effects is required. The objective of this study was to assess the knowledge of workers in outdoor professions on the effects of natural UV radiation and methods of protection against exposure. Forty outdoor workers were given a standardized questionnaire designed to ascertain their level of knowledge. The majority of participants knew exposure to solar radiation can be detrimental depending on exposure time. Eighty-three percentage recognized that people working regularly in an outdoor environment may be at risk due to high exposure. Long-sleeved clothing plus headgear and sunscreen containing sun-protecting substances were deemed adequate methods of protection by 83% and 85% respectively. Seventy percentage of the outdoor workers were familiar with the definition of the sun protection factor (SPF), yet only 25% correctly identified the amount of sunscreen needed to achieve the SPF as indicated on the product. A mere 8% of participants knew that symptoms of a sunburn first became apparent 3 h after sun exposure and only 18% were able to accurately gauge the amount of time they could spend in the sun before developing one. Although 30% had heard of the ultraviolet index (UVI), only 13% understood that protecting your skin using additional measures is recommended as of UVI 3. Overall, 30% of the outdoor workers thought themselves sufficiently protected against the harmful effects of the sun. While the participants of this study had a basic fundamental understanding of the effects of solar radiation and methods of protection against exposure, there remains an urgent need for further clarification across all demographic groups. PMID- 26995022 TI - CONSENSUS REPORT: Recognizing non-melanoma skin cancer, including actinic keratosis, as an occupational disease - A Call to Action. AB - 1. Non-melanoma skin cancer (NMSC) is by far the most common cancer diagnosed in westernized countries, and one of the few almost preventable cancers if detected and treated early as up to 90% of NMSC may be attributed to excessive exposure to ultraviolet radiation. 2. The incidence of NMSC is increasing: 2-3 million people are diagnosed worldwide annually, with an average yearly increase of 3-8% among white populations in Australia, Europe, the US and Canada over the last 30 years. 3. The link between solar ultraviolet (UV) radiation and certain forms of NMSC is clearly recognized. It is estimated that outdoor workers are exposed to an UV radiation dose 2-3 times higher than indoor workers, and there is a growing body of research linking UV radiation exposure in outdoor workers to NMSC: I. Occupationally UV-exposed workers are at least at a 43% higher risk of basal cell carcinoma (BCC) and almost doubled risk of squamous cell carcinoma (SCC) compared to the average population, with risk increasing with decreasing latitude. II. The risk for BCC, SCC and actinic keratosis (AK) among workers who have worked outdoors for more than 5 years is 3-fold higher than the risk among those with no years of working outdoors. 4. Primary prevention, early detection, treatment and regular follow-up of skin cancer (NMSC and melanoma) are shown to be beneficial from a health economic perspective. 5. Action is needed at international, European and national level to legislate for recognizing AK and NMSC as an occupational disease, which has the potential to improve access to compensation and drive preventative activities. 6. This report is a Call to Action for: I. The engagement of key stakeholders, including supranational institutions, national governments, trade organizations, employers, workers and patient organizations to drive change in prevention and protection of at-risk groups. II. Employers should be obliged to prevent outdoor worker's UV exposure from exceeding limit values, and to implement occupational skin cancer screening programmes among the at-risk workforce. III. Educational programmes for the outdoor workforce are needed to improve health literacy and drive behavioural change. IV. Nationally, steps to improve notifications and surveillance of skin cancers through both occupational services and public health programmes are required. V. Future research activities should focus on the precise definition of at-risk groups among outdoor workers through increased data gathering, including UV-dosimetry, and evaluation. PMID- 26995023 TI - The European Status Quo in legal recognition and patient-care services of occupational skin cancer. AB - BACKGROUND: Skin cancer is the most common malignancy in Caucasian populations worldwide and ultraviolet radiation (UVR) is known for being the number one carcinogen. As, especially in outdoor workers, UVR is an inevitable carcinogen, the prevention and management of UVR-related skin cancers in these at-risk populations represent a collective challenge for dermatologists and healthcare policymakers likewise. OBJECTIVE: To provide an overview on the current regulations on the acknowledgement and management of work-related skin cancer in 11 European countries. METHODS: Dermatologists from 11 countries networking within the EU Horizon 2020 COST Action TD1206 'StanDerm' contributed to a standardized survey regarding current national regulations, implemented for the recognition, prevention and management as well as possible compensation regulations in their individual country of residence. RESULTS: Ten of 11 participating countries in this survey reported the existence of an established programme available on certain occupational diseases; work-related skin diseases were only specifically recognized in eight countries. Seven of 11 countries recognize cutaneous squamous cell carcinoma in outdoor workers as 'occupational skin cancer'. Basal cell carcinoma (6 of 11), actinic keratosis (5 of 11), Bowen's disease (5 of 11) and malignant melanoma (5 of 11) are not as regularly approved as potentially 'work-induced'. Only a few of the countries included into this survey established a general documentation system (national registry) on occupational skin diseases. So far, representatives of only three countries of this survey referred to a specific established national programme for the prevention, management or compensation of occupational skin cancers acquired during work-related UVR exposure. CONCLUSION: This survey highlights the need for mandatory regulations on the prevention, management and potential compensation of work-related UV-induced skin cancer across Europe. Against the background of a joint European domestic market, equal standards of occupational safety across Europe should include binding regulations for the protection and management of work-related skin cancer. The design of a common regulation to meet the increasing incidence of skin cancers in outdoor workers should become part of the European agenda, ensuring equal working and living conditions in the member states. PMID- 26995024 TI - 10-Hz Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex Reduces Heroin Cue Craving in Long-Term Addicts. PMID- 26995025 TI - Effects of Echinococcus multilocularis miR-71 mimics on murine macrophage RAW264.7 cells. AB - The microRNAs (miRNAs) are a class of small regulatory non-coding RNA that contributes to the activation of host-pathogen cross-talk during infection. In helminthes, miR-71 is highly conserved and it has recently been detected in nematode exosomes, as well as in the sera and/or fluids of infected humans and mice. However, the role of miR-71 during infection remains poorly characterized. Herein, we show that Ago1 and Ago4, which encode key components of the small RNA induced silencing complex (RISC), were up-regulated in murine macrophage RAW264.7 cells transfected by Echinococcus multilocularis miR-71 (emu-miR-71) mimics. Using a miRNA PCR array, none of the 84 miRNAs involved in inflammation or autoimmunity were significantly up- or down-regulated in the transfected cells (p>0.05). Although it did not influence IL-10 production by the treated cells (p>0.05), the mimics significantly repressed the production of NO 12 h after treatment with LPS and IFN-gamma (p<0.01), identifying another potential mechanism whereby parasites can carefully regulate host levels of NO. These findings indicate that the release of parasite-derived miR-71 into hosts can affect the functions of macrophages, and possibly represents an exciting direction for studies of the interplay between parasites and hosts. PMID- 26995026 TI - Antifungal curcumin promotes chitin accumulation associated with decreased virulence of Sporothrix schenckii. AB - Curcumin, a yellow polyphenol compound, is known to possess antifungal activity for a range of pathogenic fungi. However, the fungicidal mechanism of curcumin (CUR) has not been identified. We have occasionally found that chitin redistributes to the cell wall outer layer of Sporothrix schenckii (S. schenckii) upon sublethal CUR treatment. Whether CUR can affect chitin synthesis via the protein kinase C (PKC) signaling pathway has not been investigated. This study describes a direct fungicidal activity of CUR against S. schenckii demonstrated by the results of a checkerboard microdilution assay and, for the first time, a synergistic effect of CUR with terbinafine (TRB). Furthermore, the results of real-time PCR showed that sublethal CUR upregulated the transcription of PKC, chitin synthase1 (CHS1), and chitin synthase3 (CHS3) in S. schenckii. The fluorescence staining results using wheat germ agglutinin-fluorescein isothiocyanate (WGA-FITC) and calcofluor white (CFW) consistently showed that chitin exposure and total chitin content were increased on the conidial cell wall of S. schenckii by sublethal CUR treatment. A histopathological analysis of mice infected with CUR-treated conidia showed dampened inflammation in the local lesion and a reduced fungal burden. The ELISA results showed proinflammatory cytokine secretion at an early stage from macrophages stimulated by the CUR treated conidia. The present data led to the conclusion that CUR is a potential antifungal agent and that its fungicidal mechanism may involve chitin accumulation on the cell wall of S. schenckii, which is associated with decreased virulence in infected mice. PMID- 26995027 TI - Identification of mutated driver pathways in cancer using a multi-objective optimization model. AB - New-generation high-throughput technologies, including next-generation sequencing technology, have been extensively applied to solve biological problems. As a result, large cancer genomics projects such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium are producing large amount of rich and diverse data in multiple cancer types. The identification of mutated driver genes and driver pathways from these data is a significant challenge. Genome aberrations in cancer cells can be divided into two types: random 'passenger mutation' and functional 'driver mutation'. In this paper, we introduced a Multi objective Optimization model based on a Genetic Algorithm (MOGA) to solve the maximum weight submatrix problem, which can be employed to identify driver genes and driver pathways promoting cancer proliferation. The maximum weight submatrix problem defined to find mutated driver pathways is based on two specific properties, i.e., high coverage and high exclusivity. The multi-objective optimization model can adjust the trade-off between high coverage and high exclusivity. We proposed an integrative model by combining gene expression data and mutation data to improve the performance of the MOGA algorithm in a biological context. PMID- 26995028 TI - Effects of gender on ketamine-induced conditioned placed preference and urine metabonomics. AB - OBJECTIVE: The aim of this study was to examine whether or not there was a gender difference in CPP (conditioned placed preference) induced by ketamine and to further explore the effect of sex on metabolic responses to ketamine inducing in SD rats. METHODS: We measured ketamine-induced conditioned place preference and ketamine-induced metabolic changes in urine by using (1)H nuclear magnetic resonance (NMR) coupled with principal component analysis (PCA), partial least squares (PLS) and orthogonal signal correction (OSC) analysis. RESULTS: In the CPP experiment, ketamine served as a positive reinforcing agent in both male and female rats, but, in particularly, the preference score of female rats was significantly higher than that of male rats. Compared with male rats, the metabolic trajectory fluctuation of the female rats was relatively larger. At the same time, different metabolites (1, 3-dimethyluric acid, cysteine-S-sulfate, glyceraldehydes, glycine, ribitol, acetoacetic acid, creatine, 3-methyladenine, hypotaurine, taurine, dimethylglycine and theobromine) between male and female rats were found. CONCLUSIONS: Female Sprague-Dawley rats were more sensitive to the ketamine-induced CPP than male rats. The fluctuation ranges of metabolic trajectory and metabolite contents in urine were both different between female and male rats. This would provide targeted suggestions for ketamine abuser, for example, men and women should take different drug withdrawal therapeutic methods. PMID- 26995030 TI - A static organization in a dynamic context--A qualitative study of changes in working conditions for Swedish engine officers. AB - During the last decades the shipping industry has undergone rapid technical developments and experienced hard economic conditions and increased striving for profitability. This has led to reduced staffing and changes in task performance, which has been reported to increase workload for the remaining seafarers. The working conditions on board have a number of distinct and in many ways unique characteristics, which makes the job demands and resources for seafarers unique in several ways. The purpose of this study was to assess how engine room staff perceives how these major technical and organizational changes in the shipping industry have affected job demands as well as resources. The study compiled individual interviews and focus groups interviews with engine crew members where they were asked to elaborate on the psychosocial work environment and the major changes in the working conditions on board. Engine crew describes a work situation where they feel a lack of resources. The content of the work has changed, staffing has been reduced, new tasks are being added but the organization of the crew and the design of the work place remains unaltered. PMID- 26995029 TI - Residues and dissipation kinetics of carbendazim and diethofencarb in tomato (Lycopersicon esculentum Mill.) and intake risk assessment. AB - Dissipation behaviors and residues of carbendazim and diethofencarb in combination in tomato were investigated. The half-lives were 2.1-3.4 days for carbendazim, and 1.8-3.2 days for diethofencarb at a dose of 1.5 times of the recommended dosage. The residues of carbendazim and diethofencarb were below the maximum residue limits (MRLs) in China one day after application of the combination. The ultimate residues were significantly lower than the maximum permissible intake (MPI) in China at the recommended high dose for both child and adult. The values of the maximum dietary exposure for carbendazim and diethofencarb were 0.26 and 0.27 mg per person per day, respectively. The theoretical maximum daily intake (TMDI) values for carbendazim and diethofencarb were 1.5 and 0.5 mg/day, respectively. The dietary exposure was lower than the MPI, which indicates the harvested tomato samples under the experimental conditions (open field) are safe for human consumption at the recommended high dosage of the wettable powder. PMID- 26995031 TI - A model for developing job rotation schedules that eliminate sequential high workloads and minimize between-worker variability in cumulative daily workloads: Application to automotive assembly lines. AB - The aim of study is to suggest a job rotation schedule by developing a mathematical model in order to reduce cumulative workload from the successive use of the same body region. Workload assessment using rapid entire body assessment (REBA) was performed for the model in three automotive assembly lines of chassis, trim, and finishing to identify which body part exposed to relatively high workloads at workstations. The workloads were incorporated to the model to develop a job rotation schedule. The proposed schedules prevent the exposure to high workloads successively on the same body region and minimized between-worker variance in cumulative daily workload. Whereas some of workers were successively assigned to high workload workstation under no job rotation and serial job rotation. This model would help to reduce the potential for work-related musculoskeletal disorders (WMSDs) without additional cost for engineering work, although it may need more computational time and relative complex job rotation sequences. PMID- 26995032 TI - Combining situated Cognitive Engineering with a novel testing method in a case study comparing two infusion pump interfaces. AB - We validated the usability of a new infusion pump interface designed with a situated Cognitive Engineering approach by comparing it to a reference interface using a novel testing method employing repeated measurements and process measures, in addition to traditional outcome measures. The sample consisted of 25 nurses who performed eight critical tasks three times. Performance measures consisted of number and type of errors, deviations from a pre-established normative path solution, task completion times, number of keystrokes, mental effort and preferences in use. Results showed that interaction with the new interface resulted in 18% fewer errors, 90% fewer normative path deviations, 42% lower task completion times, 40% fewer keystrokes, 39% lower mental effort and 76% more subjective preferences in use. These outcomes suggest that within the scope of this case study, combining the situated Cognitive Engineering approach with a novel testing method addresses various shortcomings of earlier testing methods. PMID- 26995033 TI - Soccer players' fitting perception of different upper boot materials. AB - The present study assessed the influence of upper boot materials on fitting perception. Twenty players tested three soccer boots only differing in the upper boot material (natural calf leather, natural kangaroo leather and synthetic leather). Players reported fitting perception and preference on specific foot areas using a perceived fitting scale. Ratings were averaged for every foot area. Repeated measures ANOVA was used to analyze the differences between boots. The kangaroo leather boots were perceived tighter and closer to the preferred fitting in general fitting, metatarsals area and instep area. The synthetic leather boots were perceived as the loosest and as the most distant boot from the preferred fitting in medial front area and instep area. In conclusion, the type of upper boot material influences the fitting perception of soccer players. The kangaroo leather was the material whose fitting was perceived closest to the players fitting preference. PMID- 26995034 TI - Ecodriving in hybrid electric vehicles--Exploring challenges for user-energy interaction. AB - Hybrid electric vehicles (HEVs) can help to reduce transport emissions; however, user behaviour has a significant effect on the energy savings actually achieved in everyday usage. The present research aimed to advance understanding of HEV drivers' ecodriving strategies, and the challenges for optimal user-energy interaction. We conducted interviews with 39 HEV drivers who achieved above average fuel efficiencies. Regression analyses showed that technical system knowledge and ecodriving motivation were both important predictors for ecodriving efficiency. Qualitative data analyses showed that drivers used a plethora of ecodriving strategies and had diverse conceptualisations of HEV energy efficiency regarding aspects such as the efficiency of actively utilizing electric energy or the efficiency of different acceleration strategies. Drivers also reported several false beliefs regarding HEV energy efficiency that could impair ecodriving efforts. Results indicate that ecodriving support systems should facilitate anticipatory driving and help users locate and maintain drivetrain states of maximum efficiency. PMID- 26995035 TI - Optimization of healthcare supply chain in context of macro-ergonomics factors by a unique mathematical programming approach. AB - This study presents an integrated approach for analyzing the impact of macro ergonomics factors in healthcare supply chain (HCSC) by data envelopment analysis (DEA). The case of this study is the supply chain (SC) of a real hospital. Thus, healthcare standards and macro-ergonomics factors are considered to be modeled by the mathematical programming approach. Over 28 subsidiary SC divisions with parallel missions and objectives are evaluated by analyzing inputs and outputs through DEA. Each division in this HCSC is considered as decision making unit (DMU). This approach can analyze the impact of macro-ergonomics factors on supply chain management (SCM) in healthcare sector. Also, this method ranks the relevant performance efficiencies of each HCSC. In this study by using proposed method, the most effective macro-ergonomics factor on HCSC is identified as "teamwork" issue. Also, this study would help managers to identify the areas of weaknesses in their SCM system and set improvement target plan for the related SCM system in healthcare industry. To the best of our knowledge, this is the first study for macro-ergonomics optimization of HCSC. PMID- 26995036 TI - Soldier-relevant body borne load impacts minimum foot clearance during obstacle negotiation. AB - Soldiers often trip and fall on duty, resulting in injury. This study examined ten male soldiers' ability to negotiate an obstacle. Participants had lead and trail foot minimum foot clearance (MFC) parameters quantified while crossing a low (305 mm) and high (457 mm) obstacle with (19.4 kg) and without (6 kg) body borne load. To minimize tripping risk, participants increased lead foot MFC (p = 0.028) and reduced lead (p = 0.044) and trail (p = 0.035) foot variability when negotiating an obstacle with body borne load. While obstacle height had no effect on MFC (p = 0.273 and p = 0.126), placing the trail foot closer to the high obstacle when crossing with body borne load, resulted in greater lead (R = 0.640, b = 0.241, p = 0.046) and trail (R = 0.636, b = 0.287, p = 0.048) MFC. Soldiers, when carrying typical military loads, may be able to minimize their risk of tripping over an obstacle by creating a safety margin via greater foot clearance with reduced variability. PMID- 26995037 TI - Exploring sub-optimal use of an electronic risk assessment tool for venous thromboembolism. AB - International guidelines and consensus groups recommend using a risk assessment tool (RAT) to assess Venous Thromboembolism (VTE) risk prior to the prescription of prophylaxis. We set out to examine how an electronic RAT was being used (i.e. if by the right clinician, at the right time, for the right purpose) and to identify factors influencing utilization of the RAT. A sample of 112 risk assessments was audited and 12 prescribers were interviewed. The RAT was used as intended in only 40 (35.7%) cases (i.e. completed by a doctor within 24 h of admission, prior to the prescription of prophylaxis). We identified several reasons for sub-optimal use of the RAT, including beliefs about the need for a RAT, poor awareness of the tool, and poor RAT design. If a user-centred approach had been adopted, it is likely that a RAT would not have been implemented or that problematic design issues would have been identified. PMID- 26995038 TI - Exposure-response relationships for work-related neck and shoulder musculoskeletal disorders--Analyses of pooled uniform data sets. AB - There is a lack of quantitative data regarding exposure-response relationships between occupational risk factors and musculoskeletal disorders in the neck and shoulders. We explored such relationships in pooled data from a series of our cross-sectional studies. We recorded the prevalence of complaints/discomfort (Nordic Questionnaire) and diagnoses (physical examination) in 33 groups (24 female and 9 male) within which the workers had similar work tasks (3141 workers, of which 817 were males). In representative sub-groups, we recorded postures and velocities of the head (N = 299) and right upper arm (inclinometry; N = 306), right wrist postures and velocities (electrogoniometry; N = 499), and muscular activity (electromyography) in the right trapezius muscle (N = 431) and forearm extensors (N = 206). We also assessed the psychosocial work environment (Job Content Questionnaire). Uni- and multivariate linear meta-regression analysis revealed several statistically significant group-wise associations. Neck disorders were associated with head inclination, upper arm elevation, muscle activity of the trapezius and forearm extensors and wrist posture and angular velocity. Right-side shoulder disorders were associated with head and upper arm velocity, activity in the trapezius and forearm extensor muscles and wrist posture and angular velocity. The psychosocial work environment (low job control, job strain and isostrain) was also associated with disorders. Women exhibited a higher prevalence of neck and shoulder complaints and tension neck syndrome than men, when adjusting for postures, velocities, muscular activity or psychosocial exposure. In conclusion, the analyses established quantitative exposure-response relationships between neck and shoulder disorders and objective measures of the physical workload on the arm. Such information can be used for risk assessment in different occupations/work tasks, to establish quantitative exposure limits, and for the evaluation of preventive measures. PMID- 26995039 TI - Categorisation of visualisation methods to support the design of Human-Computer Interaction Systems. AB - During the design of Human-Computer Interaction (HCI) systems, the creation of visual artefacts forms an important part of design. On one hand producing a visual artefact has a number of advantages: it helps designers to externalise their thought and acts as a common language between different stakeholders. On the other hand, if an inappropriate visualisation method is employed it could hinder the design process. To support the design of HCI systems, this paper reviews the categorisation of visualisation methods used in HCI. A keyword search is conducted to identify a) current HCI design methods, b) approaches of selecting these methods. The resulting design methods are filtered to create a list of just visualisation methods. These are then categorised using the approaches identified in (b). As a result 23 HCI visualisation methods are identified and categorised in 5 selection approaches (The Recipient, Primary Purpose, Visual Archetype, Interaction Type, and The Design Process). PMID- 26995040 TI - Validity of a small low-cost triaxial accelerometer with integrated logger for uncomplicated measurements of postures and movements of head, upper back and upper arms. AB - Repetitive work and work in constrained postures are risk factors for developing musculoskeletal disorders. Low-cost, user-friendly technical methods to quantify these risks are needed. The aims were to validate inclination angles and velocities of one model of the new generation of accelerometers with integrated data loggers against a previously validated one, and to compare meaurements when using a plain reference posture with that of a standardized one. All mean (n = 12 subjects) angular RMS-differences in 4 work tasks and 4 body parts were <2.5 degrees and all mean median angular velocity differences <5.0 degrees /s. The mean correlation between the inclination signal-pairs was 0.996. This model of the new generation of triaxial accelerometers proved to be comparable to the validated accelerometer using a data logger. This makes it well-suited, for both researchers and practitioners, to measure postures and movements during work. Further work is needed for validation of the plain reference posture for upper arms. PMID- 26995041 TI - Using event related potentials to identify a user's behavioural intention aroused by product form design. AB - The capacity of product form to arouse user's behavioural intention plays a decisive role in further user experience, even in purchase decision, while traditional methods rarely give a fully understanding of user experience evoked by product form, especially the feeling of anticipated use of product. Behavioural intention aroused by product form designs has not yet been investigated electrophysiologically. Hence event related potentials (ERPs) were applied to explore the process of behavioural intention when users browsed different smart phone form designs with brand and price not taken into account for mainly studying the brain activity evoked by variety of product forms. Smart phone pictures with different anticipated user experience were displayed with equiprobability randomly. Participants were asked to click the left mouse button when certain picture gave them a feeling of behavioural intention to interact with. The brain signal of each participant was recorded by Curry 7.0. The results show that pictures with an ability to arouse participants' behavioural intention for further experience can evoke enhanced N300 and LPPs (late positive potentials) in central-parietal, parietal and occipital regions. The scalp topography shows that central-parietal, parietal and occipital regions are more activated. The results indicate that the discrepancy of ERPs can reflect the neural activities of behavioural intention formed or not. Moreover, amplitude of ERPs occurred in corresponding brain areas can be used to measure user experience. The exploring of neural correlated with behavioural intention provide an accurate measurement method of user's perception and help marketers to know which product can arouse users' behavioural intention, maybe taken as an evaluating indicator of product design. PMID- 26995042 TI - Predicting stretcher carriage: Investigating variations in bilateral carry tests. AB - Carrying a casualty on a stretcher is a critical task within military and emergency service occupations. This study evaluated the impact of manipulating carry speed and the object type in bilateral carries on the ability to predict performance and reflect the physical and physiological requirements of a unilateral stretcher carry. We demonstrated that three task-related predictive tests; a jerry can carry performed at 4.5 km h(-1)or 5.0 km h(-1) and a kettle bell carry performed at 5.0 km h(-1) were strongly predictive of the physical and physiological demands of an individual participating as part of a four-person stretcher carry team. Therefore, bilateral predictive assessments have the utility for predicting the suitability of employees to effectively and safely conduct a four-person unilateral stretcher carry. PMID- 26995043 TI - Effect of an on-hip load-carrying belt on physiological and perceptual responses during bimanual anterior load carriage. AB - Manual load carriage continues to be a major contributor of musculoskeletal injury. This study investigates the physiological and subjective effects of an on hip load-carrying belt (HLCB) during bimanual anterior load carriage. Fifteen healthy male participants walked on a level ground treadmill at 4.5 km/h for 5 min carrying 5, 10 and 15 kg loads with hands and arms in front of the body, with and without using the HLCB (WD and ND). Heart rate, normalized oxygen uptake, minute ventilation and, central and peripheral ratings of perceived exertion were the dependent variables. The mean heart rate, normalized oxygen uptake, minute ventilation and peripheral rating of perceived exertion increased significantly with load under both WD and ND conditions. At a load of 15 kg, the mean heart rate, normalized oxygen uptake, minute ventilation and peripheral rating of perceived exertion were significantly lower by 6.6%, 8.0%, 11.8% and 13.9% respectively in WD condition when compared to the ND condition. There was no significant difference between WD and ND conditions with 5 or 10 kg load. It can be concluded that the HLCB could reduce a person's physiological and peripheral perceptual responses when walking on a level ground treadmill at 4.5 km/h with a load of 15 kg. Using a HLCB or similar device is therefore recommended for bimanual anterior load carriage for loads of 15 kg or probably larger. PMID- 26995044 TI - Driving without wings: The effect of different digital mirror locations on the visual behaviour, performance and opinions of drivers. AB - Drivers' awareness of the rearward road scene is critical when contemplating or executing lane-change manoeuvres, such as overtaking. Preliminary investigations have speculated on the use of rear-facing cameras to relay images to displays mounted inside the car to create 'digital mirrors'. These may overcome many of the limitations associated with traditional 'wing' and rear-view mirrors, yet will inevitably effect drivers' normal visual scanning behaviour, and may force them to consider the rearward road scene from an unfamiliar perspective that is incongruent with their mental model of the outside world. We describe a study conducted within a medium-fidelity simulator aiming to explore the visual behaviour, driving performance and opinions of drivers while using internally located digital mirrors during different overtaking manoeuvres. Using a generic UK motorway scenario, thirty-eight experienced drivers conducted overtaking manoeuvres using each of five different layouts of digital mirrors with varying degrees of 'real-world' mapping. The results showed reductions in decision time for lane changes and eyes-off road time while using the digital mirrors, when compared with baseline traditional reflective mirrors, suggesting that digital displays may enable drivers to more rapidly pick up the salient information from the rearward road scene. Subjectively, drivers preferred configurations that most closely matched existing mirror locations, where aspects of real-world mapping were largely preserved. The research highlights important human factors issues that require further investigation prior to further development/implementation of digital mirrors within vehicles. Future work should also aim to validate findings within real-world on-road environments whilst considering the effects of digital mirrors on other important visual behaviour characteristics, such as depth perception. PMID- 26995045 TI - Differences in vision performance in different scenarios and implications for design. AB - To design accessibly, designers need good, relevant population data on visual abilities. However, currently available data often focuses on clinical vision measures that are not entirely relevant to everyday product use. This paper presents data from a pilot survey of 362 participants in the UK, covering a range of vision measures of particular relevance to product design. The results from the different measures are compared, and recommendations are given for relative text sizes to use in different situations. The results indicate that text needs to be 17-18% larger for comfortable rather than perceived threshold viewing, and a further 20% larger when users are expected to wear their everyday vision setup rather than specific reading aids. PMID- 26995046 TI - What makes icons appealing? The role of processing fluency in predicting icon appeal in different task contexts. AB - Although icons appear on almost all interfaces, there is a paucity of research examining the determinants of icon appeal. The experiments reported here examined the icon characteristics determining appeal and the extent to which processing fluency - the subjective ease with which individuals process information - was used as a heuristic to guide appeal evaluations. Participants searched for, and identified, icons in displays. The initial appeal of icons was held constant while ease of processing was manipulated by systematically varying the complexity and familiarity of the icons presented and the type of task participants were asked to carry out. Processing fluency reliably influenced users' appeal ratings and appeared to be based on users' unconscious awareness of the ease with which they carried out experimental tasks. PMID- 26995047 TI - Estimation of inertial parameters of the lower trunk in pregnant Japanese women: A longitudinal comparative study and application to motion analysis. AB - We aimed to quantify the inertial parameters of the lower trunk segment in pregnant Japanese women and compare kinetic data during tasks calculated with parameters estimated in this study to data calculated with standard parameters. Eight pregnant women and seven nulliparous women participated. Twenty-four infrared reflective markers were attached to the lower trunk, and the standing position was captured by eight infrared cameras. The lower trunk was divided into parts, and inertial parameters were calculated. Pregnant women performed a movement task that involved standing from a chair, picking up plates, and walking forward after turning to the right. Kinetic analysis was performed using standard inertial parameters and the newly calculated parameters. There were more significant differences between methods in the kinetic data at the latter stages of pregnancy. The inertial parameters calculated in this study should be used to ensure the validity of biomechanical studies of pregnant Japanese women. PMID- 26995048 TI - Does drywall installers' innovative idea reduce the ergonomic exposures of ceiling installation: A field case study. AB - OBJECTIVE: The study was conducted to assess an intervention suggested by the workers to reduce the physical or ergonomic exposures of the drywall installation task. METHODS: The drywall installers were asked to brainstorm on innovative ideas that could reduce their ergonomic exposures during the drywall installation work. The workers proposed the idea of using a 'deadman' (narrow panel piece) to hold the panels to the ceiling while installing them. The researcher collected quantitative exposure data (PATH, 3DSSPP) at the baseline and intervention phases and compared the phases to find out any change in the exposure while using the 'deadman'. RESULTS: Results showed that ergonomic exposures (such as overhead arm and awkward trunk postures and heavy load handling) were reduced at the intervention phase while using the 'deadman' with an electrically operated lift. CONCLUSION: The concept of the 'deadman', which was shown to help reduce musculoskeletal exposures during ceiling installation, can be used to fabricate a permanent ergonomic tool to support the ceiling drywall panel. PMID- 26995049 TI - The Helmet Fit Index--An intelligent tool for fit assessment and design customisation. AB - Helmet safety benefits are reduced if the headgear is poorly fitted on the wearer's head. At present, there are no industry standards available to assess objectively how a specific protective helmet fits a particular person. A proper fit is typically defined as a small and uniform distance between the helmet liner and the wearer's head shape, with a broad coverage of the head area. This paper presents a novel method to investigate and compare fitting accuracy of helmets based on 3D anthropometry, reverse engineering techniques and computational analysis. The Helmet Fit Index (HFI) that provides a fit score on a scale from 0 (excessively poor fit) to 100 (perfect fit) was compared with subjective fit assessments of surveyed cyclists. Results in this study showed that quantitative (HFI) and qualitative (participants' feelings) data were related when comparing three commercially available bicycle helmets. Findings also demonstrated that females and Asian people have lower fit scores than males and Caucasians, respectively. The HFI could provide detailed understanding of helmet efficiency regarding fit and could be used during helmet design and development phases. PMID- 26995050 TI - Observer performance in estimating upper arm elevation angles under ideal viewing conditions when assisted by posture matching software. AB - Selecting a suitable body posture measurement method requires performance indices of candidate tools. Such data are lacking for observational assessments made at a high degree of resolution. The aim of this study was to determine the performance (bias and between- and within-observer variance) of novice observers estimating upper arm elevation postures assisted by posture matching software to the nearest degree from still images taken under ideal conditions. Estimates were minimally biased from true angles: the mean error across observers was less than 2 degrees . Variance between observers was minimal. Considerable variance within observers, however, underlined the risk of relying on single observations. Observers were more proficient at estimating 0 degrees and 90 degrees postures, and less proficient at 60 degrees . Thus, under ideal visual conditions observers, on average, proved proficient at high resolution posture estimates; further investigation is required to determine how non-optimal image conditions, as would be expected from occupational data, impact proficiency. PMID- 26995051 TI - Dermoscopic Findings of Jellyfish Stings Caused by Pelagia noctiluca. AB - BACKGROUND AND OBJECTIVES: Jellyfish are free-living members of the phylum Cnidaria who share a specialized stinging cell, the cnidocyte. Pelagia noctiluca is the most frequent and toxic jellyfish species found in the Balearic beaches and cnidocytes are arranged in pigmented clusters called "warts". Dermoscopy continues to expand its use much beyond the pigmentary lesions and to date, there is no data regarding dermoscopic findings in jellyfish stings. The aim of the present work was to study the dermoscopic findings of jellyfish stings in the island of Mallorca. PATIENTS AND METHODS: We retrospectively reviewed the clinical and dermoscopic images of 25 episodes of jellyfish stings caused by P. noctiluca that occurred between 2009 and 2015. RESULTS: Overall, the following dermoscopic features were found: brown dots (84%), pinkish hue (56%), pinpoint brown crusts (44%), scale-crust (40%), brown "Chinese characters pattern" (32%), "serpentine" ulceration (28%), linear purpura (20%), and whitish-yellow crusts (15%). Vessels were mainly dotted (36%) or reticular (16%). Scale-crust, serpentine ulceration and pinkish hue were significantly more frequent in lesions older than 2 days. CONCLUSIONS AND LIMITATIONS: Our study identifies 4 dermoscopic features that may represent the contact with P. noctiluca cnidocytes: brown dots, brown "Chinese characters pattern", pinpoint brown crusts and whitish yellow crusts. A peculiar finding of "serpentine ulceration" with brown dots would be very suggestive of P. noctiluca sting. We believe dermoscopy is a valuable tool in the diagnosis of jellyfish stings when a clear history of contact is lacking. Further studies are needed to validate our findings in other jellyfish species. PMID- 26995052 TI - Atorvastatin inhibits miR-143 expression: A protective mechanism against oxidative stress in cardiomyocytes. PMID- 26995053 TI - Frequency and prognostic significance of access site and non-access site bleeding and impact of choice of antithrombin therapy in patients undergoing primary percutaneous coronary intervention. The EUROMAX trial. AB - BACKGROUND: The overall impact of post percutaneous coronary intervention (PCI) bleeding on long term prognosis after acute coronary syndromes (ACS) has been established, but it may differ between access and non-access related bleeding events. The impact of antithrombin choice on bleeding may also differ according to the origin of the bleed. We sought to determine the origin of bleeding relative to the access site, its prognostic significance and the respective impact of antithrombin therapy in the EUROMAX trial. METHODS: We performed a blinded review of the case records of all TIMI major or minor bleeds in the EUROMAX trial and assigned them in one of 2 categories: access site bleeds (ASB), or rest of bleeds (ROB). Incidence of bleeding for each category was assessed according to randomization to antithrombotic treatment. RESULTS: A total of 231 out of 2198 patients suffered a TIMI major/minor bleed (10.5%) and ASB accounted for 48.5%, while ROB for 51.5% of the bleeds. Thirty day mortality was 2.5% (50/1967) for patients without a bleed, 2.7% (3/112, p=0.76 vs. no bleed) for patients with ASB, and 10.9% (13/119, p<0.0001 vs. no bleed) for ROB patients. The use of bivalirudin reduced both ASB and ROB with relative risk reductions of 34% and 46% respectively. CONCLUSIONS: In contemporary primary PCI, bleeding originates with equal frequency either at or away from the access site. Access site bleeds were not associated with an excess in 30day mortality, but the rest of the bleeds were. Bivalirudin is associated with a lower risk of bleeding irrespective of origin. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01087723. PMID- 26995060 TI - Corrigendum. PMID- 26995054 TI - ROS and intracellular ion channels. AB - Oxidative stress is a well-known driver of numerous pathological processes involving protein and lipid peroxidation and DNA damage. The resulting increase of pro-apoptotic pressure drives tissue damage in a host of conditions, including ischemic stroke and reperfusion injury, diabetes, death in acute pancreatitis and neurodegenerative diseases. Somewhat less frequently discussed, but arguably as important, is the signaling function of oxidative stress stemming from the ability of oxidative stress to modulate ion channel activity. The evidence for the modulation of the intracellular ion channels and transporters by oxidative stress is constantly emerging and such evidence suggests new regulatory and pathological circuits that can be explored towards new treatments for diseases in which oxidative stress is an issue. In this review we summarize the current knowledge on the effects of oxidative stress on the intracellular ion channels and transporters and their role in cell function. PMID- 26995055 TI - Functional role of TRP channels in modulating ER stress and Autophagy. AB - Intracellular calcium (Ca(2+)) levels play a vital role in regulating cellular fate. The coordination and interrelation among the cellular organelles, mainly the intracellular Ca(2+) stores in endoplasmic reticulum (ER), are crucial in maintaining cytosolic Ca(2+) levels and in general cellular homeostasis. Moreover, maintaining Ca(2+) homeostasis is essential for regulating diverse and sometimes opposing processes such as cell survival and cell death in disease conditions such as, neurodegeneration, cancer and aging. Ca(2+) is able to regulate opposing functions by either regulating the cellular "self-eating" phenomenon of autophagy to promote cell survival or by regulating the programmed cell death process of apoptosis. Autophagy is also important for cell survival especially after induction of ER stress and association between ER stress and autophagy may have relevance to numerous diseases. Moreover, a multitude of evidence is emerging that the functional regulation of TRP channels, their unique localization, and their interaction with other Ca(2+)-sensing elements define these diverse regulatory pathways. It is this unique function which allows individual TRP channels to contribute differently in the regulation of cell fate and, in turn, determines the precise effect of modulating Ca(2+) signaling via the particular channel. Thus, in this review we have focused on the aspects of TRP channel localization and function (Ca(2+) signaling) that affects the ER stress and autophagic process. PMID- 26995062 TI - Comparative avoidance behaviour of the earthworm Eisenia fetida towards chloride, nitrate and sulphate salts of Cd, Cu and Zn using filter paper and extruded water agar gels as exposure media. AB - We studied the avoidance behaviour of the earthworm Eisenia fetida towards Cd, Cu, and Zn, trace elements (TEs) tested as chloride, nitrate and sulphate salts. Sub adults were exposed individually using dual-cell chambers at 20+2 degrees C in the dark. Recordings were realised at different dates from 2h to 32h. We used filter paper and extruded water agar gel as exposure media to evaluate the contribution of the dermal and the digestive exposure routes on the avoidance reactions. Exposures to Cu or Cd (10mgmetal ionL(-1)) resulted in highly significant avoidance reactions through the exposure duration. Worms avoided Zn poorly and reactions towards Zn salts varied along the exposure. Worm sensitivity towards TEs differed between salts and this could result from differential toxicity or accessibility of these TE salts to earthworms. The anion in itself was not the determinant of the avoidance reactions since exposures to similar concentrations of these anions using calcium salts did not result in significant avoidance worm behaviour. Avoidance responses towards TEs were higher in the case of water agar exposures than in filter paper exposures. Thus, dermal contacts with TE solutions would elicit worm avoidance but signals from receptors located inside the digestive tract could reinforce this behaviour. The use of extruded water agar gels as the substrate allows checking the real sensitivity of earthworm species towards TEs since the TE concentrations leading to significant avoidance reactions were below those reported in the literature when using TE spiked soils. PMID- 26995056 TI - Calcium and reactive oxygen species in regulation of the mitochondrial permeability transition and of programmed cell death in yeast. AB - Mitochondria-dependent programmed cell death (PCD) in yeast shares many features with the intrinsic apoptotic pathway of mammals. With many stimuli, increased cytosolic [Ca(2+)] and ROS generation are the triggering signals that lead to mitochondrial permeabilization and release of proapoptotic factors, which initiates yeast PCD. While in mammals the permeability transition pore (PTP), a high-conductance inner membrane channel activated by increased matrix Ca(2+) and oxidative stress, is recognized as part of this signaling cascade, whether a similar process occurs in yeast is still debated. The potential role of the PTP in yeast PCD has generally been overlooked because yeast mitochondria lack the Ca(2+) uniporter, which in mammals allows rapid equilibration of cytosolic Ca(2+) with the matrix. In this short review we discuss the nature of the yeast permeability transition and reevaluate its potential role in the effector phase of yeast PCD triggered by Ca(2+) and oxidative stress. PMID- 26995061 TI - Bevacizumab and cetuximab with conventional chemotherapy reduced pancreatic tumor weight in mouse pancreatic cancer xenografts. AB - Pancreatic cancer remains the fourth leading cause of cancer-related death in the USA with a 5-year survival rate of 5 %. The effects of epidermal growth factor receptor and vascular endothelial growth factor A blockade with chemotherapy on pancreatic tumor growth were examined. Mice bearing human PANC-1 cell xenografts were divided into three groups: T-CR (gemcitabine, cisplatin, and 5 fluorouracil), T-TR (cetuximab, bevacizumab, gemcitabine, cisplatin, and 5 fluorouracil), and vehicle control (T). The therapies were administered via intraperitoneal injections every 4 days for seven cycles from 7 weeks after cancer cell implantation. Mice treated with T-TR had significant reductions in tumor weight as compared to the control group (p < 0.05). Although mice in the T CR group experienced a significant reduction in body weight gain, serum albumin, and gastrocnemius muscle mass (p < 0.05), no such reductions were observed in the T-TR group. Mice treated with T-TR had slightly increased CD11c+ DC and CD49b+ NK cell levels in the spleen (p < 0.05) and significantly lower tumor VEGF expression (p < 0.05). Tumor carcinoembryonic antigen expression was significantly reduced in both treatment groups (p < 0.05). Thus, addition of bevacizumab and cetuximab to gemcitabine, cisplatin, and fluorouracil may represent an effective treatment option for pancreatic cancer that warrants further study. PMID- 26995063 TI - Chemical composition, toxicity and non-target effects of Pinus kesiya essential oil: An eco-friendly and novel larvicide against malaria, dengue and lymphatic filariasis mosquito vectors. AB - Mosquitoes (Diptera: Culicidae) are vectors of important parasites and pathogens causing death, poverty and social disability worldwide, with special reference to tropical and subtropical countries. The overuse of synthetic insecticides to control mosquito vectors lead to resistance, adverse environmental effects and high operational costs. Therefore, the development of eco-friendly control tools is an important public health challenge. In this study, the mosquito larvicidal activity of Pinus kesiya leaf essential oil (EO) was evaluated against the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti and the lymphatic filariasis vector Culex quinquefasciatus. The chemical composition of the EO was analyzed by gas chromatography-mass spectroscopy. GC-MS revealed that the P. kesiya EO contained 18 compounds. Major constituents were alpha-pinene, beta-pinene, myrcene and germacrene D. In acute toxicity assays, the EO showed significant toxicity against early third-stage larvae of An. stephensi, Ae. aegypti and Cx. quinquefasciatus, with LC50 values of 52, 57, and 62ug/ml, respectively. Notably, the EO was safer towards several aquatic non-target organisms Anisops bouvieri, Diplonychus indicus and Gambusia affinis, with LC50 values ranging from 4135 to 8390ug/ml. Overall, this research adds basic knowledge to develop newer and safer natural larvicides from Pinaceae plants against malaria, dengue and filariasis mosquito vectors. PMID- 26995064 TI - A simple agroinfiltration method for transient gene expression in plant leaf discs. AB - In the present study, we developed a simple transient gene expression system based on Agrobacterium-mediated transformation. Vacuum infiltration was applied to leaf discs from Nicotiana benthamiana plants with Agrobacterium suspension solution under conventional vacuum conditions in a needleless plastic syringe. Model proteins, green fluorescent protein, beta-glucuronidase, mouse granulocyte macrophage colony-stimulating factor, and human fibroblast growth factor 1 were successfully expressed in leaf discs within 4 days after infiltration. In addition, the functional evaluation of viral RNA silencing suppressors, Artichoke mottled crinkle virus p19 protein, was also performed. Using this method, the contamination and diffusion of genetically modified bacterium to the environment and important transgenic plants were prevented. This method can be conducted without specialized apparatuses or large amounts of Agrobacterium suspension solutions; thus, the simultaneous evaluation of multiple vectors will be easily possible. PMID- 26995065 TI - Bitter taste receptors: Novel insights into the biochemistry and pharmacology. AB - Bitter taste receptors (T2Rs) belong to the super family of G protein-coupled receptors (GPCRs). There are 25 T2Rs expressed in humans, and these interact with a large and diverse group of bitter ligands. T2Rs are expressed in many extra oral tissues and can perform diverse physiological roles. Structure-function studies led to the identification of similarities and dissimilarities between T2Rs and Class A GPCRs including amino acid conservation and novel motifs. However, the efficacy of most of the T2R ligands is not yet elucidated and the biochemical pharmacology of T2Rs is poorly understood. Recent studies on T2Rs characterized novel ligands including blockers for these receptors that include inverse agonist and antagonists. In this review we discuss the techniques used for elucidating bitter blockers, concept of ligand bias, generic amino acid numbering, the role of cholesterol, and conserved water molecules in the biochemistry and pharmacology of T2Rs. PMID- 26995066 TI - Caretaker Quality of Life in Rett Syndrome: Disorder Features and Psychological Predictors. AB - OBJECTIVE: Rett syndrome is a severe neurodevelopmental disorder affecting approximately one in 10,000 female births. The clinical features of Rett syndrome are known to impact both patients' and caretakers' quality of life in Rett syndrome. We hypothesized that more severe clinical features would negatively impact caretaker physical quality of life but would positively impact caretaker mental quality of life. METHODS: Participants were individuals enrolled in the Rett Natural History Study with a diagnosis of classic Rett syndrome. Demographic data, clinical disease features, caretaker quality of life, and measures of family function were assessed during clinic visits. The Optum SF-36v2 Health Survey was used to assess caretaker physical and mental quality of life (higher scores indicate better quality of life). Descriptive, univariate, and multivariate analyses were used to characterize relationships between child and caretaker characteristics and caretaker quality of life. RESULTS: Caretaker physical component scores (PCS) were higher than mental component scores (MCS): 52.8 (9.7) vs 44.5 (12.1). No differences were demonstrated between the baseline and 5-year follow-up. In univariate analyses, disease severity was associated with poorer PCS (P = 0.006) and improved MCS (P = 0.003). Feeding problems were associated with poorer PCS (P = 0.007) and poorer MCS (P = 0.018). In multivariate analyses, limitations in caretaker personal time and home conflict adversely affected PCS. Feeding problems adversely impacted MCS. CONCLUSIONS: Caretaker quality of life in Rett syndrome is similar to that for caretakers in other chronic diseases. Disease characteristics significantly impact quality of life, and feeding difficulties may represent an important clinical target for improving both child and caretaker quality of life. The stability of quality-of life scores between baseline and five years adds important value. PMID- 26995067 TI - A Study of a Cohort of X-Linked Myotubular Myopathy at the Clinical, Histologic, and Genetic Levels. AB - BACKGROUND: Myotubular myopathy is a rare X-linked congenital myopathy characterized by marked neonatal hypotonia and respiratory insufficiency, facial and ocular involvement, and muscle biopsy with prominent central nuclei in the majority of muscle fibers. It is caused by mutations in MTM1, which codes for the phosphoinositides phosphatase myotubularin. In this work, we established and detailed a new cohort of six patients at the clinical, histologic, and genetic levels. PATIENTS AND METHODS: Patients were recruited after screening 3065 muscle biopsy reports from two large biopsy banks in Sao Paulo, Brazil from the years 2008 to 2013, and from referrals to a neuromuscular outpatient clinic between 2011 and 2013. We reviewed biopsy slides, evaluated patients, and Sanger sequenced MTM1 in the families. RESULTS: All patients but one had classic phenotypes with a stable course after a severe onset. Two patients died suddenly from hypovolemic shock. Muscle biopsies had been performed in five patients, all of whom showed a classic pattern with a predominance of centrally located nuclei and increased oxidative activity in the center of the fibers. Two patients showed necklace fibers, and two families had novel truncating mutations in MTM1. CONCLUSIONS: X-linked myotubular myopathy is rare in the Brazilian population. Necklace fibers might be more prevalent in this condition than previously reported. Direct Sanger sequencing of MTM1 on clinical suspicion avoids the need of a muscle biopsy. PMID- 26995068 TI - Pyridoxine-Dependent Epilepsy: An Expanding Clinical Spectrum. AB - BACKGROUND: Pyridoxine-dependent epilepsy is a rare autosomal recessive epileptic encephalopathy caused by antiquitin (ALDH7A1) deficiency. In spite of adequate seizure control, 75% of patients suffer intellectual developmental disability. Antiquitin deficiency affects lysine catabolism resulting in accumulation of alpha-aminoadipic semialdehyde/pyrroline 6' carboxylate and pipecolic acid. Beside neonatal refractory epileptic encephalopathy, numerous neurological manifestations and metabolic/biochemical findings have been reported. METHODS AND RESULTS: We present a phenotypic spectrum of antiquitin deficiency based on a literature review (2006 to 2015) of reports (n = 49) describing the clinical presentation of confirmed patients (n > 200) and a further six patient vignettes. Possible presentations include perinatal asphyxia; neonatal withdrawal syndrome; sepsis; enterocolitis; hypoglycemia; neuroimaging abnormalities (corpus callosum and cerebellar abnormalities, hemorrhage, white matter lesions); biochemical abnormalities (lactic acidosis, electrolyte disturbances, neurotransmitter abnormalities); and seizure response to pyridoxine, pyridoxal-phosphate, and folinic acid dietary interventions. DISCUSSION: The phenotypic spectrum of pyridoxine-dependent epilepsy is wide, including a myriad of neurological and systemic symptoms. Its hallmark feature is refractory seizures during the first year of life. Given its amenability to treatment with lysine-lowering strategies in addition to pyridoxine supplementation for optimal seizure control and developmental outcomes, early diagnosis of pyridoxine-dependent epilepsy is essential. All infants presenting with unexplained seizures should be screened for antiquitin deficiency by determination of alpha-aminoadipic semialdehyde/pyrroline 6' carboxylate (in urine, plasma or cerebrospinal fluid) and ALDH7A1 molecular analysis. PMID- 26995069 TI - Prevalence and Characteristics of Vaccination Triggered Seizures in Dravet Syndrome in Hong Kong: A Retrospective Study. AB - BACKGROUND: Dravet syndrome is a rare epileptic encephalopathy characterized by treatment-resistant polymorphic seizures. Seizure onset usually occurs during the first year of life, and seizures are often associated with heat-related triggering factors (e.g., fever, photosensitivity, or hot bath). It has been reported that children with Dravet syndrome often present with recurrent febrile seizures and vaccination-related seizures. METHODS: We analyzed the occurrence of vaccination-related seizures (defined as the development of a seizure within 48 hours post vaccination) in 54 patients with Dravet syndrome. Patients were divided into two groups according to whether seizures occurred within 48 hours of vaccination (i.e., vaccination-proximate group) or not (vaccination-distant group). RESULTS: There was no significant difference in the vaccination-proximate group and vaccination-distant group for the presence of SCN1A mutation. In our Dravet syndrome cohort, the vaccination-proximate group consisted of 17 (31.5%) patients with Dravet syndrome. Thus vaccination-related seizures are a common triggering factor in Dravet syndrome, reported in up to one third of our patients. CONCLUSION: Vaccination-related seizures may act as the triggering factor for the onset of seizures in children with Dravet syndrome, especially before the definitive diagnosis of Dravet syndrome can be made within the first year of life. We suggest further study of guidelines and protocols for the prevention and management of vaccination-related seizures in children with recurrent febrile seizures pending a definitive diagnosis of Dravet syndrome in the first 12 months of life. PMID- 26995071 TI - [Management of soft tissues sarcoma of the limbs by external beam radiation therapy]. AB - Soft tissue sarcomas are rare tumours. Conservative surgery followed by postoperative radiation therapy represents the gold standard in the majority of cases. Postoperative radiotherapy improves local control without affecting survival. Besides the quality of surgical excision, which remains the major prognostic factor, the importance of the irradiation volume and particularly margins used in external beam radiotherapy were also found to influence local control of the disease. In this study, we propose to conduct a literature review on the present state of our knowledge on this subject in the form of an articulated controversy: in favour or opposed to large margins in external radiotherapy. PMID- 26995070 TI - Fgf3 and Fgf16 expression patterns define spatial and temporal domains in the developing chick inner ear. AB - The inner ear is a morphologically complex sensory structure with auditory and vestibular functions. The developing otic epithelium gives rise to neurosensory and non-sensory elements of the adult membranous labyrinth. Extrinsic and intrinsic signals manage the patterning and cell specification of the developing otic epithelium by establishing lineage-restricted compartments defined in turn by differential expression of regulatory genes. FGF3 and FGF16 are excellent candidates to govern these developmental events. Using the chick inner ear, we show that Fgf3 expression is present in the borders of all developing cristae. Strong Fgf16 expression was detected in a portion of the developing vertical and horizontal pouches, whereas the cristae show weaker or undetected Fgf16 expression at different developmental stages. Concerning the rest of the vestibular sensory elements, both the utricular and saccular maculae were Fgf3 positive. Interestingly, strong Fgf16 expression delimited these Fgf16-negative sensory patches. The Fgf3-negative macula neglecta and the Fgf3-positive macula lagena were included within weakly Fgf16-expressing areas. Therefore, different FGF-mediated mechanisms might regulate the specification of the anterior (utricular and saccular) and posterior (neglecta and lagena) maculae. In the developing cochlear duct, dynamic Fgf3 and Fgf16 expression suggests their cooperation in the early specification and later cell differentiation in the hearing system. The requirement of Fgf3 and Fgf16 genes in endolymphatic apparatus development and neurogenesis are discussed. Based on these observations, FGF3 and FGF16 seem to be key signaling pathways that control the inner ear plan by defining epithelial identities within the developing otic epithelium. PMID- 26995072 TI - Risk factors for early renal dysfunction following endovascular aortic aneurysm repair and its effect on the postoperative outcome. AB - PURPOSE: Renal insufficiency is associated with increased morbidity and death after endovascular aortic aneurysm repair (EVAR). However, the effect of postoperative acute kidney dysfunction on patient outcome has not been fully determined. This study aimed to determine the risk factors of early postoperative renal function decline using chronic kidney disease (CKD) staging and its effect on the clinical outcome. METHODS: A retrospective analysis was performed on a prospectively maintained EVAR database. Pre- and postoperative CKD stages were determined for all patients according to the estimated glomerular filtration rate values. RESULTS: We identified 135 patients who were treated with elective EVAR. CKD stage decline was observed in 25 (19 %) of the patients. Freedom from aneurysm-related death was significantly lower in patients with postoperative CKD progression compared with those with unchanged CKD stage. A shaggy aorta without oral beta-blocker administration and higher preoperative serum creatinine levels (>1.4 mg/dL) were found to be independent predictors of an early postoperative CKD stage decline. CONCLUSIONS: Patients with postoperative CKD progression have an increased frequency of aneurysm-related death. The presence of a shaggy aorta, absence of oral beta-blocker administration and an increased preoperative creatinine level are independent predictors of early postoperative CKD progression. PMID- 26995073 TI - Maximal blood flow acceleration analysis in the early diastolic phase for aortocoronary artery bypass grafts: a new transit-time flow measurement predictor of graft failure following coronary artery bypass grafting. AB - PURPOSE: Maximal graft flow acceleration (max df/dt) determined using transit time flowmetry (TTFM) in the diastolic phase was assessed as a potential predictor of graft failure for aortocoronary artery (AC) bypass grafts in coronary artery bypass patients. METHODS: Max df/dt was retrospectively measured in 114 aortocoronary artery bypass grafts. TTFM data were fitted to a 9 polynomial curve, which was derived from the first-derivative curve, to measure max df/dt (9-polynomial max df/dt). Abnormal TTFM was defined as a mean flow of <15 ml/min, a pulsatility index of >5 or a diastolic filling ratio of <50 %. Postoperative assessments were routinely performed by coronary artery angiography (CAG) at 1 year after surgery. RESULTS: Using TTFM, 68 grafts were normal, 4 of which were failing on CAG, and 46 grafts were abnormal, 21 of which were failing on CAG. 9-polynomial max df/dt was significantly lower in abnormal TTFM/failing by the CAG group compared with abnormal TTFM/patent by the CAG group (1.08 +/- 0.89 vs. 2.05 +/- 1.51 ml/s(2), respectively; P < 0.01, Mann-Whitney U test, Holm adjustment). CONCLUSIONS: TTFM 9-polynomial max df/dt in the early diastolic phase may be a promising predictor of future graft failure for AC bypass grafts, particularly in abnormal TTFM grafts. PMID- 26995074 TI - [Evaluation of the efficacy of aflibercept's in the treatment of neovascular age related macular degeneration in treatment-naive and switched patients. Report of 86 cases]. AB - INTRODUCTION: AMD (age-related macular degeneration) is the leading cause of legal blindness after age 50 in developed countries. Anti-VEGF therapy by intravitreal injection has become the standard for the treatment of neovascular AMD. Ranibizumab is the most currently used, but the arrival of aflibercept on the market 1 year ago is changing clinical practices in France. METHODS: The objective of this study is to evaluate the efficacy of aflibercept in AMD. All patients with neovascular AMD undergoing IVT (intra-vitreal injection) of aflibercept were included. All patients had at baseline and on follow-up visits a measurement of best corrected visual acuity (ETDRS), a fundus examination and an OCT. For statistical analysis, we analyzed the data at 0, 3, 6 and 12 months. An induction phase was carried out for treatment-naive patients, and follow-up was performed according to the PRN method (Pro Re Nata). The total number of injections over the entire follow-up period was recorded. RESULTS: Ninety-six eyes were included, with 17 treatment-naive patients and 69 patients who had previously received ranibizumab. At 1 year, all patients had a mean improvement of 5.4 ETDRS letters (P=0.0026). The OCT data showed a rapid decline in retinal thickness, from baseline to the third month, of 143 microns on average (P=5.6*10( 15)); between the 3rd and 6th month, this was slower, with an average decrease of 4.6 microns, and between the 6th and the 12th month, the difference was significant, with an average decrease of 36 microns (P=0.003). The number of injections over one year was 5.7 on average. CONCLUSION: The efficacy of aflibercept with a PRN protocol provides interesting results, with an improvement in visual acuity and central retinal thickness in all treated groups, and with fewer injections than advocated. PMID- 26995075 TI - The effect of repeat 360-degree selective laser trabeculoplasty on intraocular pressure control in open-angle glaucoma. AB - OBJECTIVE: To evaluate the effect of repeat 360-degree selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) with short-term follow-up. METHODS: This study was based on clinical practice (25 females and 13 males) with a history of primary open-angle glaucoma (27), normotensive glaucoma (6) or pseudoexfoliative glaucoma (5). We measured the IOP at baseline before the first and second 360-degree SLT at 1 month, 6 months and 15 months. Follow-up was concluded earlier if the SLT failed (an increase in IOP over the baseline value), if a new medication was introduced or if an IOP lowering surgery was performed. RESULTS: Baseline IOP prior to SLT1 was 19.0 +/- 3.7 mmHg, which dropped to 16.0 +/- 3.7 mmHg (17.0% reduction), 16.9 +/- 3.8 mmHg (12.5% reduction) and 17.2 +/- 3.3 mmHg (8.7% reduction) at 1, 6 and 15 months respectively (P<0.01). For SLT2, baseline IOP was 18.0 +/- 4.5 mmHg, which dropped to 15.1 +/- 3.8 mmHg (15.1% reduction), 15.1 +/- 4.3 mmHg (15.6% reduction) and 16.0 +/- 3.6 mmHg (10.3% reduction) at 1, 6 and 15 months respectively (P<0.01). CONCLUSION: In a cohort of patients who underwent 360-degree SLT 4 years previously, a second SLT resulted in IOP lowering similar to the first treatment with a possibly more sustained response. PMID- 26995076 TI - [Intravitreal bevacizumab in AMD complicated by submacular hemorrhage]. AB - PURPOSE: To evaluate functional and anatomic results of intravitreal bevacizumab as monotherapy at 12 and 24 months in patients with neovascular age-related macular degeneration (AMD) complicated by large submacular hemorrhage. METHODS: Retrospective analysis of a total of 21 patients (22 eyes) with large submacular hemorrhage secondary to age-related macular degeneration between May 2008 and December 2011. Patients were treated with three monthly intravitreal bevacizumab injections (1.25mg/0.05 mL) at a four to six week interval and then PRN. Retreatment was based on the presence of hemorrhage on fundus examination or signs of activity on optical coherence tomography. Changes from baseline best corrected visual acuity (BCVA) scores, central retinal thickness, volume of hemorrhage and number of injections were analyzed. RESULTS: The mean patient age was 72 years (range, 60-89 years). All patients completed at least 12 months of follow-up, and 17 patients fulfilled 24 months. The size of hemorrhage varied from 3 to 9 disc areas with a mean duration of 12.8 days. At baseline, mean initial BCVA was 20/400 (1.3 LogMAR) and improved to 20/160 at 12 months (P<0.001) and 20/164 at 24 months (P<0.001). Mean central retinal thickness decreased significantly from 550 MUm to 255 MUm at 24 months (P<0.001). The mean number of injections was 3.87 during the first 12 months. No case of recurrent bleeding was detected during the second year. CONCLUSION: Intravitreal bevacizumab may be a beneficial approach for the management of large submacular hemorrhage secondary to AMD. PMID- 26995077 TI - [Efficacy of corneal cross-linking for the treatment of keratoconus]. AB - Keratoconus (KC) is a complex disease whose pathophysiology is only partially understood. The priority in management is to halt the progression of corneal deformation as soon as possible in the course of KC disease. Corneal cross linking (CXL) is at present the only dedicated treatment for this purpose. Its biochemical mechanism of action leads to changes in the viscoelastic properties of the cornea induced by matrix bonding and renewal of keratocytes. The effect of CXL is difficult to quantify when measured in in-vivo conditions because of a lack of consistent tools adapted for clinical practice. Nevertheless, a large amount of evidence has been collected so far confirming the positive action of CXL on corneal structural reinforcement, and numerous studies have demonstrated significant efficacy in halting progression of KC with long-term follow-up. Published studies, however, are of relatively low scientific power given the great heterogeneity of the disease and the numerous associated biases in evaluation. The purpose of this paper is to summarize the consistent evidence of efficacy of CXL and to justify its role in our therapeutic armamentarium for management of progressive KC. PMID- 26995078 TI - [External ophthalmomyiasis in Morocco: About a case in an urban area]. PMID- 26995079 TI - [Role of SD-OCT in the diagnosis and prognosis of macular hypoplasia in nystagmus patients]. AB - PURPOSE: To investigate whether spectral domain optical coherence tomography (SD OCT) is helpful for the diagnosis and prognosis of foveal hypoplasia in patients with overt nystagmus. METHODS: A retrospective cross-sectional study was conducted in 48 patients with overt nystagmus. All patients underwent a complete ophthalmic examination including best corrected visual acuity, biomicroscopic and fundus examinations. Spectral domain optical coherence tomography was performed using 3D OCT-2000 FA PLUS Topcon, Tokyo, Japan, for the diagnosis and grading of foveal hypoplasia, using the Thomas classification, and its possible correlation with visual acuity. RESULTS: Foveal hypoplasia was diagnosed in 6 patients (12.5%). The mean age of the patients was 13.2 years (10-18 years). Mean visual acuity was 1.53/10 (0.87 LogMAR). Foveal hypoplasia was associated with aniridia in 2 patients, albinism in 3 patients and keratoconus in 1 case. On SD-OCT, foveal hypoplasia was grade 4 in 4 patients and grade 3 in 2 patients. Mean visual acuity was 2.55/10 in patients with grade 3 foveal hypoplasia and 1.22/10 in patients with grade 4 foveal hypoplasia, and the difference in visual acuity between the two groups was statistically significant (P<0.001). CONCLUSION: SD OCT plays a double role in the diagnosis and prognosis of foveal hypoplasia in patients with nystagmus. PMID- 26995080 TI - Impact of dermatologic adverse events induced by targeted therapies on quality of life. AB - BACKGROUND: Investigations about the impact of dermatologic adverse events on quality of life in the context of targeted therapies are quite recent and results vary in some dimensions. This article aims to summarize the existing data and to clarify needs in terms of clinical management and future research. METHODS: A literature review was done with Pubmed, Medline, Scopus and PsycInfo databases and it combined the empirical studies published in English and in French over the past ten years. RESULTS AND CONCLUSIONS: Dermatologic adverse events globally have a low to moderate impact on quality of life, mainly in the physical and emotional domains. Reasons for inter-individual variations in adjustment and long term impact are still not well known. Making quality of life assessments systematic, making early referrals of patients to dermatology consultations and giving more attention to individual experience were identified as measures that could help prevent deterioration in quality of life. PMID- 26995081 TI - Treatment that follows guidelines closely dramatically improves overall survival of patients with anal canal and margin cancers. AB - BACKGROUND: To assess relevance of ESMO-ESSO-ESTRO treatment guidelines in a retrospective analysis of patients with anal canal or anal margin cancers. MATERIAL AND METHODS: 155 patients were separated into standard treatment group (STG), treated according to or closely the guidelines, and an altered treatment group (ATG). RESULTS: The median follow-up time was 50.7 months. In the STG, the 5- and 10-year LR-DFS rates were 75.2% and 72.7%; in the ATG, they were 66.8% and 61.2%, respectively. In the STG, the 5- and 10-year OS rates were 81.8% and 68%; in the ATG, they were 63.3% and 49.5%, respectively (p=0.037). In the multivariate analysis, favorable prognostic factors for OS included the standard treatment, age <60, tumor 50.4Gy. CONCLUSION: This study identifies the superiority of treatment according to standard guidelines compared to altered treatment. Our results corroborate the guidelines. PMID- 26995082 TI - Fever of unknown origin in cancer patients. AB - Fever of unknown origin (FUO) remains a challenging clinical problem, namely in patients with cancer. In cancer patients, FUO may be due to the cancer itself, as it is the case of hematological malignancies; digestive tumors (colon cancer, liver metastases) are significantly associated with FUO and infection can be demonstrated in some cases. Prevention with G-CSF and empirical antimicrobial therapy are essential approaches for the management of FUO in cancer patients. New diagnostic approaches, such as PET imaging, should be further evaluated in cancer patients with FUO. PMID- 26995083 TI - Translational neuropathic pain research: A clinical perspective. AB - Neuropathic pain encompasses a broad range of conditions associated with a lesion or disease of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-8%. The interest in the pathophysiology of neuropathic pain has increased over the last two decades with an exponential increase in the number of experimental studies. However, despite the hopes raised by scientific discoveries, there has been no rational development of a truly new class of drugs. This situation revealing the limitations of certain experimental models, also results of limitations in clinical research. One of the reasons for the therapeutic difficulties in these patients is probably due to the fact that treatments are used in a uniform fashion whatever the clinical picture, while these syndromes are in fact highly heterogeneous. Clinical advances have recently been made in this field, following the validation of new specific clinical tools and the standardization of quantitative sensory testing paradigms facilitating improvements in the clinical characterization of these syndromes. It has been clearly demonstrated that neuropathic pain is a consistent clinical entity, but it is multidimensional in terms of its clinical expression, with different sensory profiles, potentially reflecting specific pathophysiological mechanisms. This new conceptualization of neuropathic pain should improve the characterization of the responder profiles in clinical trials and provide valuable information for the development of new and more clinically sound translational approaches in experimental models in animals. PMID- 26995084 TI - The relationship of bone-tumor-induced spinal cord astrocyte activation and aromatase expression to mechanical hyperalgesia and cold hypersensitivity in intact female and ovariectomized mice. AB - Recently, our group established a relationship between tumor-induced spinal cord astrocyte activation and aromatase expression and the development of bone tumor nociception in male mice. As an extension of this work, we now report on the association of tumor-induced mechanical hyperalgesia and cold hypersensitivity to changes in spinal cord dorsal horn GFAP and aromatase expression in intact (INT) female mice and the effect of ovariectomy on these parameters. Implantation of fibrosarcoma cells produced robust mechanical hyperalgesia in INT animals, while ovariectomized (OVX) females had significantly less mechanical hyperalgesia. Cold hypersensitivity was apparent by post-implantation day 7 in INT and OVX females compared to their saline-injected controls and increased throughout the experiment. The decrease in mechanical hyperalgesia in OVX females was mirrored by significant decreases in spinal astrocyte activity in laminae I-II, III-IV, V VI and X and aromatase expression in laminae V-VI and X in the dorsal horn of tumor-bearing animals. Administration of the aromatase inhibitor letrozole reduced tumor-induced hyperalgesia in INT females only suggesting that the tumor induced increase in aromatase expression and its associated increase in spinal estrogen play a role in the development of bone tumor-induced hyperalgesia. Finally, intrathecal (i.t.) administration of 17beta-estradiol caused a significant increase in tumor-induced hyperalgesia in INT tumor-bearing females. Since i.t. 17beta-estradiol increases tumor pain and ovariectomy significantly decreases tumor pain, as well as spinal aromatase, estrogen may play a critical role in the spinal cord response to the changing tumor environment and the development of tumor-induced nociception. PMID- 26995085 TI - Low-cost, real-time, continuous flow PCR system for pathogen detection. AB - In this paper, we present a portable and low cost point-of-care (POC) PCR system for quantitative detection of pathogens. Our system is based on continuous flow PCR which maintains fixed temperatures zones and pushes the PCR solution between two heated areas allowing for faster heat transfer and as a result, a faster PCR. The PCR system is built around a 46.0 mm * 30.9 mm * 0.4 mm disposable thermoplastic chip. In order to make the single-use chip economically viable, it was manufactured by hot embossing and was designed to be compatible with roll-to roll embossing for large scale production. The prototype instrumentation surrounding the chip includes two heaters, thermal sensors, and an optical system. The optical system allows for pathogen detection via real time fluorescence measurements. FAM probes were used as fluorescent reporters of the amplicons generated during the PCR. To demonstrate the function of the chip, two infectious bacteria targets were selected: Chlamydia trachomatis and Escherichia coli O157:H7. For both bacteria, the limit of detection of the system was determined, PCR efficiencies were calculated, and different flow velocities were tested. We have demonstrated successful detection for these two bacterial pathogens highlighting the versatility and broad utility of our portable, low cost, and rapid PCR diagnostic device. PMID- 26995086 TI - RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis. AB - Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1alpha production. Injection of anti-IL-1alpha antibody protects against the progress of atherosclerosis in ApoE -/- mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibition of necrosis may yield novel therapeutic targets for treatment in years to come. PMID- 26995087 TI - The Parkinsonism-associated protein DJ-1/Park7 prevents glycation damage in human keratinocyte. AB - Reducing sugars and dicarbonyls form covalent adducts with proteins through a nonenzymatic process known as glycation, which inactivates proteins, is increased in diabetic patients and is associated with diabetic complications, including retinopathy, cataracts, nephropathy, neuropathy, cardiomyopathy and skin defects. We recently characterized DJ-1/Park7 as a protein deglycase that repairs proteins from glycation by glyoxal and methylglyoxal, two major glycating agents which are responsible for up to 65% of glycation events. In this study, we investigated the ability of DJ-1 to prevent protein glycation in keratinocytes. Glycation of collagen and keratinocyte proteins was tested by measuring ultraviolet absorption and fluorescence emission. Protein glycation in HaCaT keratinocytes was investigated by immunodetection with anti-advanced glycation endproduct antibodies, after DJ-1 depletion or overexpression. In vitro, DJ-1 prevented glycation of collagen and keratinocyte protein extracts. In cell culture, DJ-1 depletion by small interfering RNAs resulted in a 3-fold increase in protein glycation levels. Moreover, protein glycation levels were decreased several-fold in cells overexpressing DJ-1 after addition of the Nrf2 inducer sulforaphane or after transfection with a DJ-1 plasmid. Thus, the DJ-1 deglycase plays a major role in preventing protein glycation in eukaryotic cells and might be important for preventing skin glycation. PMID- 26995088 TI - Prolyl hydroxylase 3 overexpression accelerates the progression of atherosclerosis in ApoE-/- mice. AB - PHD3 belongs to the family of 2-oxoglutarate and iron-dependent dioxygenases and is a critical regulator of HIF-1alpha. Its expression is increased in cardiovascular diseases such as cardiomyopathy, myocardial ischemia-reperfusion injury, and congestive heart failure. However, the association between PHD3 and atherosclerosis has not been clearly elucidated. In the present study, we investigated the potential effect and mechanism of PHD3 in apolipoprotein E deficient (ApoE-/-) mice. Murine PHD3 lentivirus and shRNA -PHD3 lentivirus were constructed and injected intravenously into ApoE-/- mice fed on a high fat diet. The aortic atherosclerotic lesion area was larger with PHD3 over-expression. With increased PHD3 levels, macrophages and smooth muscle cells were enhanced. The apoptosis of atherosclerotic plaques revealed an increase when PHD3 was elevated. Furthermore, the expression of intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), monocyte chemotactic protein 1 (MCP 1), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha(TNF-alpha) were upregulated with PHD3 over-expression. In vitro, we explored the specific signaling pathway of PHD3 in HUVECs. PHD3 over-expression is associated with activation of ERK1/2 and JNK phosphorylation of MAPK signaling pathway. PHD3 inhibition decreased the apoptosis of HUVECs treated with ox-LDL (50 MUg/ml). Our study suggests that PHD3 is not only a regulator of HIF-1alpha but also an active participant in atherogenesis. PMID- 26995089 TI - An easily regenerable enzyme reactor prepared from polymerized high internal phase emulsions. AB - A large-scale high-efficient enzyme reactor based on polymerized high internal phase emulsion monolith (polyHIPE) was prepared. First, a porous cross-linked polyHIPE monolith was prepared by in-situ thermal polymerization of a high internal phase emulsion containing styrene, divinylbenzene and polyglutaraldehyde. The enzyme of TPCK-Trypsin was then immobilized on the monolithic polyHIPE. The performance of the resultant enzyme reactor was assessed according to the conversion ability of Nalpha-benzoyl-l-arginine ethyl ester to Nalpha-benzoyl-l-arginine, and the protein digestibility of bovine serum albumin (BSA) and cytochrome (Cyt-C). The results showed that the prepared enzyme reactor exhibited high enzyme immobilization efficiency and fast and easy-control protein digestibility. BSA and Cyt-C could be digested in 10 min with sequence coverage of 59% and 78%, respectively. The peptides and residual protein could be easily rinsed out from reactor and the reactor could be regenerated easily with 4 M HCl without any structure destruction. Properties of multiple interconnected chambers with good permeability, fast digestion facility and easily reproducibility indicated that the polyHIPE enzyme reactor was a good selector potentially applied in proteomics and catalysis areas. PMID- 26995090 TI - Upregulation of gene expression levels of ceramide metabolic enzymes after application of sphingomyelin-based liposomes to a three-dimensional cultured human epidermis model. AB - BACKGROUND/AIMS: We have previously reported that the application of sphingomyelin-based liposomes (SM-L) to a three-dimensional cultured skin model increase the content of ceramides NS, NP, AS and AP. However, the mechanism responsible for these increased ceramide levels was not identified. METHODS: SM-L and sphingomyelinase (SMase) were combined and incubated at 37 degrees C for 24 h. SM-L were also applied to three-dimensional cultured skin for 24 h and quantification of SMase and beta-glucocerebrosidase (beta-GCase) mRNA expression levels performed using real-time PCR. Additionally, three dimensional cultured skin was incubated with SM-L and the beta-GCase inhibitor conduritol B epoxide (CBE) and the ceramide content determined by high performance thin layer chromatography. RESULTS: We observed generation of ceramide NS after reaction of SM-L and SMase. However, the other ceramide classes were not detected. Notably, SMase and beta-GCase mRNA expression levels were significantly increased in cells of the skin model following application of SM-L. The levels of ceramides NS, NP, AS and AP were decreased by treatment with CBE. However, only ceramide NS was significantly increased by treatment with CBE and SM-L in combination. CONCLUSION: These findings indicate that application of SM-L to cultured skin upregulates the expression of SMase and beta-GCase and increases ceramide content. PMID- 26995091 TI - Decreased apoptosis repressor with caspase recruitment domain confers resistance to sunitinib in renal cell carcinoma through alternate angiogenesis pathways. AB - Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby conferring drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC. PMID- 26995092 TI - Survivin-targeted nanoparticles for pancreatic tumor imaging in mouse model. AB - We investigated the potential of targeting survivin, an inhibitor of apoptosis, in visualize pancreatic tumor in mouse model using targeted magnetic nanoparticles (MNPs) and magnetic resonance imaging (MRI). Chitosan-coated MNPS and survivin antisense oligonucleotide(ASON) were conjugated to give Sur-MNPs. Accumulations of targeted, non-targeted nanoparticles or nonsense oligonucleotide MNPs (NSON-MNPs) in the liver, spleen, kidney and tumors were determined. Targeted nanoparticles were highly accumulated in BxPC-3 cells but not in non cancer cells. In vivo MRI showed a significant T2 signal reduction in tumors of mice injected with targeted nanoparticles but slight signal change in tumors of mice injected with non-targeted nanoparticles or NSON-MNPs. Prussian blue staining demonstrated highly accumulated Sur-MNPs in tumor mass compared with normal pancreatic, kidney and liver tissues. Our data show that the MNPs functionalized with ASON lead to the targeted localization in pancreatic tumors. Survivin targeted nanoparticles could be used for detection of pancreatic tumors. PMID- 26995093 TI - Catanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin. AB - Novel catanionic lipid nanosystems (CLNs) incorporating curcumin (CCM) were developed, and improvements in pharmacokinetics and enhanced anti-lung cancer activity were observed. CCM was present in a lipid matrix surrounded by cationic, anionic and zwitterionic surfactants, forming the core-shell nanosystems. Compared with free CCM, the CCM-CLNs had much higher oral and intravenous bioavailabilities due to enhanced absorption and reduced clearance. The CCM-CLNs exhibited greater cytotoxicity in Lewis lung cancer (LLC) cells, which might have been due to increased antiproliferative, proapoptotic and anti-invasive activities and induction of cell cycle arrest. The CCM-CLNs increased the antitumor efficacy of CCM and decreased the tumor growth rate in tumor-bearing mice. This is the first report of induction of apoptosis in LLC cells by CCM through the PI3K/Akt/FoxO1/Bim signaling pathway. Catanionic lipid nanocarriers show promise for the therapeutic delivery of insoluble anti-tumor drugs. PMID- 26995094 TI - Evaluation of endocytosis of silica particles used in biodegradable implants in the brain. AB - Silica nanoparticles embedded in a biodegradable scaffold have been proposed to offer several advantages when used in laser-tissue-soldering of blood vessels in the brain. During degradation, these nanoparticles are likely to be released into the surrounding brain tissue. The aim of this study was to investigate possible cellular uptake mechanism(s) of the two silica nanoparticle types in microglial cells as well as their effect on autophagy and inflammatory cytokines. The nanoparticle uptake was analysed quantitatively using high-content analysis. Nanoparticle incubation did not modulate cytokine secretion and autophagy at any time point investigated. The nanoparticles were taken up by the microglia cells in a time- and particle-dependent manner. The maximal uptake was reached after 4hours and the nanoparticles were found in the endoplasmic reticulum and lysosomes. Macropinocytosis and phagocytosis were predominantly responsible for the uptake, whereas clathrin- and caveolin-independent endocytosis were involved to a minor extent. PMID- 26995095 TI - Promises and pitfalls for recombinant oligoclonal antibodies-based therapeutics in cancer and infectious disease. AB - Monoclonal antibodies (mAbs) have revolutionized the diagnosis and treatment of many human diseases and the application of combinations of mAbs has demonstrated improved therapeutic activity in both preclinical and clinical testing. Combinations of antibodies have several advantages such as the capacities to target multiple and mutating antigens in complex pathogens and to engage varied epitopes on multiple disease-related antigens (e.g. receptors) to overcome heterogeneity and plasticity. Oligoclonal antibodies are an emerging therapeutic format in which a novel antibody combination is developed as a single drug product. Here, we will provide historical context on the use of oligoclonal antibodies in oncology and infectious diseases and will highlight practical considerations related to their preclinical and clinical development programs. PMID- 26995096 TI - Safety and efficacy of coffee enriched with inulin and dextrin on satiety and hunger in normal volunteers. AB - OBJECTIVES: This study assessed the safety and efficacy of a new beverage on suppressing hunger and improving feelings of satiety in healthy volunteers. METHODS: In the safety study, participants (n = 269) received either 1) a control beverage-coffee alone (group C); 2) the study beverage-coffee, whey protein, inulin, and dextrin (group S); or 3) an inulin-enriched beverage (I group). The study was held over a 7-d period during which participants were required to consume 2 cups of coffee a day. RESULTS: There were no significant differences between the groups in any reported adverse effects, apart from more abdominal pain after the first cup in group I versus S (P < 0.05). CONCLUSIONS: This study showed that a coffee beverage enriched with inulin, dextrin, and whey is safe and has possible benefits with regard to feelings of hunger and satiety 2 h after ingestion. PMID- 26995097 TI - Surgical treatment of substernal goiter: An analysis of 44 cases. AB - OBJECTIVE: Substernal goiters are classified as primary or secondary intrathoracic goiters. Here, we report the diagnosis, symptoms, treatment, and postoperative complications of 44 substernal goiters (2 primary mediastinal goiter and 42 secondary mediastinal goiters). METHODS: A retrospective chart review of 351 patients undergoing thyroidectomy at the Department of Otolaryngology-Head and Neck Surgery of the Tokyo Metropolitan Tama Medical Center. Between 2009 and 2015, 44 patients underwent surgery for substernal goiter. RESULTS: The frequency of primary and secondary mediastinal goiters was 0.5% and 11.9%, respectively. The preoperative symptoms were neck mass, dyspnea, and dysphagia. Eight patients were asymptomatic. Thirty-nine patients had benign masses and 5 patients had malignant masses. Most patients were operated on for adenomatous goiters (52.2%). In ten cases beyond the aortic arch, the tumors were benign and there were eight cases of adenomatous goiter. All patients underwent a successful transcervical incision without sternotomy. Even the primary intrathoracic goiters were extracted after total thyroidectomy via the cervical approach without complications. Although one case showed unilateral recurrent nerve paralysis as a postoperative complication, phonetic function improved in 6 postoperative months. No instances of postoperative bleeding or definitive hypoparathyroidism occurred, and tracheostomy was not performed in any of the cases. CONCLUSION: The cervical approach was safely performed in almost all substernal goiters without an extracervical procedure. Selected cases of primary mediastinal goiter may be excised via the cervical approach. PMID- 26995098 TI - Steroids Improve Hemodynamics in Infants With Adrenal Insufficiency After Cardiac Surgery. AB - OBJECTIVE: To investigate whether steroid replacement therapy improved hemodynamics in infants after surgery for congenital heart disease only when they develop adrenal insufficiency. The authors retrospectively investigated adrenal function and evaluated hemodynamic responses to steroid replacement therapy in infants after surgery for congenital heart disease. DESIGN: Retrospective, cohort study. SETTING: Intensive care unit in the National Cerebral and Cardiovascular Center Hospital in Japan. PATIENTS: Thirty-two neonates and infants<3 months old who underwent cardiovascular surgery. INTERVENTIONS: The patients were divided into 2 groups based on corticotropin stimulation test results: group AI with adrenal insufficiency (baseline cortisol<15 ug/dL or incremental increase after testing of<9 ug/dL, with baseline cortisol of 15-34 ug/dL); and group N with normal adrenal function. The corticotropin stimulation test was performed by injecting 3.5 ug/kg of tetracosactide acetate. Hydrocortisone (1 mg/kg) was administered every 6 hours, and hemodynamics were compared before and after steroid administration between the groups. MEASUREMENTS AND MAIN RESULTS: Seven patients were classified into group AI, and demonstrated a mean blood pressure increase from 53+/-8 mmHg before treatment to 68+/-9 mmHg 18 hours after steroid administration (p<0.01). Urine output also increased, from 2.7+/-1.0 mL/kg/h to 4.8+/-1.9 mL/kg/h (p<0.05). In group N, neither mean blood pressure nor urine output increased after steroid administration. CONCLUSIONS: After surgery for congenital heart disease, one-fifth of infants developed adrenal insufficiency. Steroid replacement therapy improved hemodynamics only in the subgroup with adrenal insufficiency. PMID- 26995099 TI - Geographical variations in adult body size and reproductive life history traits in an invasive anuran, Discoglossus pictus. AB - Variability in life history traits positively affects the establishment and expansive potential of invasive species. In the present study, we analysed the variation of body size in seven populations - two native and five invasive - of the painted frog (Discoglossus pictus, Anura: Discoglossidae), native to North Africa and introduced in southern France and the north-east of the Iberian Peninsula. Other life history traits (age at maturity, size at maturity, longevity, median age and potential reproductive lifespan) were analysed in a native and an invasive population. We observed geographic variations in adult body size, related mainly to mean annual precipitation. Thus, populations had greater body size as mean annual precipitation increased, resulting in bigger specimens in the invasive populations. Adult body size and growth rates also varied between sexes in all studied populations, with males significantly larger than females. Age distribution varied between native (1-5 years) and invasive populations (2-4 years) and also between sexes. Our results suggest that higher precipitation promotes faster growth rates and larger adult body size that could facilitate the successful establishment of invasive populations. PMID- 26995100 TI - [BRCA1 associated protein 1 (BAP1) expression in pleural diffuse malignant mesothelioma: A comparative cytological and histological analyses on 50 patients]. AB - INTRODUCTION: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD. MATERIALS AND METHODS: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis. RESULTS: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation. DISCUSSION AND CONCLUSION: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect. PMID- 26995101 TI - [A solid variant of a serous cystadenocarcinoma of the pancreas]. AB - Cystic pancreatic neoplasms concern 1 to 2% of the pancreatic tumours. The serous ones are considered benign tumours but since 1989, several pancreatic serous cystadenocarcinomas (SCAC) cases have been reported. We report the case of a SCAC with a particular pattern. An 80-year-old female patient presented a 4-cm tumour in the neck of the pancreas associated with liver lesions evoking, on imagery exams, focal nodular hyperplasia nests. A cephalic duodenopancreatectomy and a resection of the liver lesions were carried out. The gross exam showed a tumour with a pattern mostly solid and an area made of cysts. The microscopic exam displayed two patterns: the solid one, predominant, made of mild atypical clear cells, and the cystic one. The liver lesions revealed solid pattern similar to the pancreatic tumour one. The tumoral cells were cytokeratin 7, AE1/AE3 and inhibin positives. The Periodic-acid Schiff showed cytoplasmic granulations, which were digested after diasatasis. Only the presence of metastases allows distinguishing a pancreatic serous cystadenoma from a SCAC. To date, thirty cases of pancreatic SCAC have been reported. Immunohistochemistry cannot confirm the malignancy nature of the lesion but it needs to be done in order to cross out the differential diagnosis, that is pancreatic metastatic clear cell renal carcinoma. Nevertheless, it remains a pathology with good prognosis. Only two cases have been reported but ours case a predominant solid pattern. PMID- 26995102 TI - [The colloid milium: An observation associated with trichinosis]. AB - The colloid milium has four clinical forms: adult colloid milium, juvenile colloid milium, paracolloid (or nodular colloid degeneration) and pigmented colloid milium. We report the case of an adult colloid milium in a man of 56, who presented episodes of diffuse pruritus associated with myalgia and digestive disorders, indicative of trichinosis. He also developed gradually over the past 10 years, yellowish injuries in the mandibles and neck for whom histology objectified a colloid milium. Etiology and treatment are still unknown; association with a trichinosis is probably coincidental. PMID- 26995103 TI - [About 2 cases of ectopic sebaceous glands in esophagus: Endoscopic and histological correlations from biopsies and resected specimens]. AB - Sebaceous glands are cutaneous annexes located in the dermis. Focal spots of ectopy of these glands are frequently identified in ectodermal tissues: they represent Fordyce's disease. However, only a few cases of ectopic sebaceous glands have been mentioned in non-ectodermic tissue. Fordyce spots of esophageal location are unusual, and most of them have been diagnosed from biopsy specimens. We report two cases of ectopic sebaceous glands in esophagus, the first diagnosed from a resected specimen, the second from biopsies. A literature review is carried out. PMID- 26995105 TI - The prognostic role of tissue and serum MMP-1 and TIMP-1 expression in patients with non-small cell lung cancer. AB - PURPOSE: Matrix metalloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) play an important role in tumor invasion and progression. The aim of this study was to evaluate the prognostic role of MMP-1 and TIMP-1 in non-small cell lung cancer (NSCLC). To find out a potential serum biomarker, tissue and serum levels were investigated together. PATIENTS AND METHODS: For 85 surgically resected NSCLC patients who had pre-operative serum samplings, MMP-1 and TIMP-1 expression were investigated using immunohistochemistry in tumor tissue and ELISA in serum. Tumor cells and surrounding stromal cells were assessed separately. RESULTS: Higher expression of MMP-1 in tumor cells comparing to stromal cells was related to male gender (P=0.006), ever smoker (P=0.004), and pooly differentiated tumor (P=0.043). For TIMP-1, adenocarcinoma showed higher tumor cell expression, while squamous cell carcinoma showed higher stromal expression (P=0.007). Patients with high carcinoembryonic antigen (CEA) level, the presence of vascular invasion, recurrence or death showed higher serum MMP-1 level. There was no correlation between the tissue and serum levels of MMP-1 and TIMP-1. A tumor/stroma TIMP-1 intensity ratio >=1 was strongly associated with early recurrence in multivariate analysis (hazard ratio=280.55, 95% confidence intervals; 11.12-7080.45; P=0.001). High serum MMP-1 (>=3,500pg/ml) showed a trend for short overall survival (P=0.080). When serum MMP-1 was combined with CEA level or presence of vascular invasion, its prognostic implication was statistically significant (P=0.045 and P=0.015, respectively). CONCLUSION: The tumor/stroma TIMP-1 intensity ratio in tissue is useful to predict tumor recurrence. Serum MMP-1 level showed a possibility as a prognostic biomarker. PMID- 26995104 TI - Photodynamic inactivation of Candida albicans biofilm: Influence of the radiant energy and photosensitizer charge. AB - BACKGROUND: The aim of this study is to investigate the photoinactivation of C. albicans biofilm on acrylic resin discs (the standard material for dental prosthesis) using the photosensitizers Methylene Blue and a Protoporphyrin IX. METHODS: Eighteen thermally activated Methyl Methacrylate Polymers were used for the biofilm growth of Candida albicans ATCC 10231. Two photosensitizers were tested: methylene blue (50MUM) and protoporphyrin IX (10MUM). Two custom-made LEDs emitting at 660nm and 630nm with approximately 800mW each were used for the irradiation, with duration ranging from 2 to 10min. RESULTS: This study demonstrates that MB decreased the aPDT CFUs by approximately two orders of magnitude, but the protoporphyrin was ineffective. CONCLUSION: The aPDT with MB significantly reduces (but does not sterilize) the amount of CFU after 10min of irradiation, and it is not dose-dependent. The lack of effect of the protoporphyrin is likely because the negative charges of the proteoglycans present in the extracellular matrix repel the negative charges of the PS, thus preventing its diffusion in the cells. PMID- 26995107 TI - Active commuting: an easy and effective way to improve health. PMID- 26995106 TI - Active commuting and obesity in mid-life: cross-sectional, observational evidence from UK Biobank. AB - BACKGROUND: Physical inactivity is a leading cause of obesity and premature mortality. We aimed to examine the relation between active commuting and obesity in mid-life using objectively measured anthropometric data from UK Biobank. METHODS: Cross-sectional, observational data from UK Biobank were used. These were collected from individuals aged 40-69 years who visited 22 assessment centres across the UK between 2006 and 2010. Self-reported commuting method was operationalised into seven categories, ordered to reflect typical levels of physical exertion. The outcomes assessed were BMI (based on objectively measured weight and height) and percentage body fat. Hypothesised confounders were income, area deprivation, urban or rural residence, education, alcohol intake, smoking, leisure physical activity, recreational walking, occupational physical activity, general health, and limiting illness or disability. We used sex-stratified multivariate linear-regression models. FINDINGS: Final complete case sample sizes were 72 999 men and 83 667 women for the BMI outcome and 72 139 men and 82 788 women for the percentage body fat outcome. Active commuting was significantly and independently associated with reduced BMI and percentage body fat for both sexes, with a graded pattern apparent across the seven commuting categories. In fully adjusted models, compared with their car-only counterparts, mixed public and active transport commuters had significantly lower BMI (men: beta coefficient 1.00 kg/m(2) [95% CI -1.14 to -0.87], p<0.0001; women: -0.67 kg/m(2) [-0.86 to 0.47], p<0.0001), as did cycling or cycling and walking commuters (men: -1.71 kg/m(2) [95% CI -1.86 to -1.56], p<0.0001; women: -1.65 kg/m(2) [-1.92 to -1.38], p<0.0001). Similarly, compared with car-only commuters, mixed public transport and active commuters had significantly lower percentage body fat (men: -1.32% [95% CI -1.53 to -1.12], p<0.0001; women: -1.10% [-1.40 to -0.81], p<0.0001), as did cycling or cycling and walking commuters (men: -2.75% [95% CI -3.03 to 2.48], p<0.0001; women: -3.26% [-3.80 to -2.71], p<0.0001). INTERPRETATION: This study is the first to use UK Biobank data to address the topic of active commuting and obesity and shows robust, independent associations between active commuting and healthier bodyweight and composition. These findings support the case for interventions to promote active travel as a population-level policy response for prevention of obesity in mid-life. FUNDING: UK Medical Research Council. PMID- 26995108 TI - Surgical outcomes and complications of reconstructive surgery in the female congenital adrenal hyperplasia patient: What every endocrinologist should know. AB - Surgical management of classical congenital adrenal hyperplasia (CAH) in 46, XX females has evolved significantly. Virilization of the genitalia of 46, XX females with CAH begins prenatally as a result of excess fetal androgen production. Improved understanding of anatomy and surgical outcomes has driven changes in surgical techniques as well as the timing of surgery. For endocrinologists treating these patients, it is important to understand the outcome of genitoplasty, identify patients who need further treatment and direct these patients to experienced surgeons. We performed a literature search on PubMed of publications addressing CAH and genital reconstruction published in the English language from 1990 to the present. In accordance with our institutional review board, we performed a retrospective analysis of clitoroplasty and/or vaginoplasty procedures performed by a single surgeon at our institution from 1996 to 2015. We found that genital reconstruction in 46, XX CAH patients is associated with few immediate post-operative, infectious, and urinary complications. Vaginal stenosis is a common complication of vaginal reconstruction and requires evaluation by an experienced surgeon. Clitoral pain or decreased sensation can be associated with clitoral recession and clitorectomy. Outcomes in sexual satisfaction and gender identity can also be impacted by surgical technique and success. Long term follow up and patient reported feedback are crucial to our understanding and management of this special group of patients. Improved awareness and understanding of the complications of genital surgery will allow endocrinologists to know what to ask patients and be ready to provide them with a resource with the understanding and experience to help them improve their quality of life. PMID- 26995109 TI - The potential of the mevalonate pathway for enhanced isoprenoid production. AB - The cytosol-localised mevalonic acid (MVA) pathway delivers the basic isoprene unit isopentenyl diphosphate (IPP). In higher plants, this central metabolic intermediate is also synthesised by the plastid-localised methylerythritol phosphate (MEP) pathway. Both MVA and MEP pathways conspire through exchange of intermediates and regulatory interactions. Products downstream of IPP such as phytosterols, carotenoids, vitamin E, artemisinin, tanshinone and paclitaxel demonstrate antioxidant, cholesterol-reducing, anti-ageing, anticancer, antimalarial, anti-inflammatory and antibacterial activities. Other isoprenoid precursors including isoprene, isoprenol, geraniol, farnesene and farnesol are economically valuable. An update on the MVA pathway and its interaction with the MEP pathway is presented, including the improvement in the production of phytosterols and other isoprenoid derivatives. Such attempts are for instance based on the bioengineering of microbes such as Escherichia coli and Saccharomyces cerevisiae, as well as plants. The function of relevant genes in the MVA pathway that can be utilised in metabolic engineering is reviewed and future perspectives are presented. PMID- 26995110 TI - Neo-cartilage engineered from primary chondrocytes is epigenetically similar to autologous cartilage, in contrast to using mesenchymal stem cells. AB - OBJECTIVES: To compare the epigenetic landscape of 3D cell models of human primary articular chondrocytes (hPACs) and human bone-marrow derived mesenchymal stem cells (hBMSCs) and their respective autologous articular cartilage. DESIGN: Using Illumina Infinium HumanMethylation450 BeadChip arrays, the DNA methylation landscape of the different cell sources and autologous cartilage was determined. Pathway enrichment was analyzed using DAVID. RESULTS: Principal Component Analysis (PCA) of methylation data revealed separate clustering of hBMSC samples. Between hBMSCs and autologous cartilage 86,881 cytosine-phosphate-guanine dinucleotides (CpGs) (20.2%), comprising 3,034 differentially methylated regions (DMRs; Deltabeta > 0.1; with the same direction of effect), were significantly differentially methylated. In contrast, between hPACs and autologous cartilage only 5,706 CpGs (1.33%) were differentially methylated. Of interest was the finding of the transcriptionally active, hyper-methylation of a Cartilage Intermediate Layer Protein (CILP) annotated DMR (Deltabeta = 0.16) in PAC cartilage, corresponding to a profound decrease in CILP expression after in vitro culturing of hPACs as compared to autologous cartilage. CONCLUSIONS: In vitro engineered neo-cartilage tissue from primary chondrocytes, hPACs, exhibits a DNA methylation landscape that is almost identical (99% similarity) to autologous cartilage, in contrast to neo-cartilage engineered from bone marrow-derived mesenchymal stem cells (MSCs). Although hBMSCs are widely used for cartilage engineering purposes the effects of these vast differences on cartilage regeneration and long term consequences of implantation, are not known. The use of hBMSCs or hPACs for future cartilage tissue regeneration purposes should therefore be investigated in more depth in future endeavors to better understand the consequences of the differential methylome on neo-cartilage. PMID- 26995112 TI - Economical and green biodiesel production process using river snail shells derived heterogeneous catalyst and co-solvent method. AB - River snail shells-derived CaO was used as a heterogeneous catalyst to synthesize biodiesel via transesterification of palm oil with methanol. The shell materials were calcined in air at 600-1000 degrees C for 3h. Physicochemical properties of the resulting catalysts were characterized by TGA-DTG, XRD, SEM, BET, XRF, FT-IR and TPD. CaO catalyzed transesterification mechanism of palm oil into biodiesel was verified. The effects of adding a co-solvent on kinetic of the reaction and %FAME yield were investigated. %FAME yield of 98.5%+/-1.5 was achieved under the optimal conditions of catalyst/oil ratio of 5wt.%; methanol/oil molar ratio of 12:1; reaction temperature of 65 degrees C; 10%v/v of THF in methanol and reaction time of 90min. The results ascertained that river snail shells is a novel raw material for preparation of CaO catalyst and the co-solvent method successfully decreases the reaction time and biodiesel production cost. PMID- 26995111 TI - Gait analysis methods for rodent models of arthritic disorders: reviews and recommendations. AB - Gait analysis is a useful tool to understand behavioral changes in preclinical arthritis models. While observational scoring and spatiotemporal gait parameters are the most widely performed gait analyses in rodents, commercially available systems can now provide quantitative assessments of spatiotemporal patterns. However, inconsistencies remain between testing platforms, and laboratories often select different gait pattern descriptors to report in the literature. Rodent gait can also be described through kinetic and kinematic analyses, but systems to analyze rodent kinetics and kinematics are typically custom made and often require sensitive, custom equipment. While the use of rodent gait analysis rapidly expands, it is important to remember that, while rodent gait analysis is a relatively modern behavioral assay, the study of quadrupedal gait is not new. Nearly all gait parameters are correlated, and a collection of gait parameters is needed to understand a compensatory gait pattern used by the animal. As such, a change in a single gait parameter is unlikely to tell the full biomechanical story; and to effectively use gait analysis, one must consider how multiple different parameters contribute to an altered gait pattern. The goal of this article is to review rodent gait analysis techniques and provide recommendations on how to use these technologies in rodent arthritis models, including discussions on the strengths and limitations of observational scoring, spatiotemporal, kinetic, and kinematic measures. Recognizing rodent gait analysis is an evolving tool, we also provide technical recommendations we hope will improve the utility of these analyses in the future. PMID- 26995113 TI - Towards a more automatic and rapid laboratory diagnosis of von Willebrand disease. PMID- 26995114 TI - High risk features of primary colorectal carcinomas which subsequently undergo peritonectomy. AB - OBJECTIVE: Determine what portion of colorectal cancer (CRC) patients with peritoneal metastases (PM) undergoing peritonectomy would have been identified/treated if second-look surgery protocol existed for high-risk primary tumours. BACKGROUND: The prognosis of CRC PM greatly improves following peritonectomy/HIPEC. Survival remains dependent upon stage of PM and there is some knowledge of high-risk factors for its development. Subsequently, there is interest in routine second-look laparotomy to follow-up high-risk CRC patients so to 'prevent' PM. METHODS: Patients were retrospectively selected from the St George database, all of whom had had PM recurrence after primary CRC resection thus underwent peritonectomy/HIPEC. Each patient's primary tumour pathology was obtained with incidence of high-risk stage (T4), macroscopic (peritoneal involvement, ovarian metastases, perforated primary) and microscopic (mucinous, signet ring) features noted. RESULTS: 125 patients were included. At primary diagnosis, 34.4%, 46.4% and 19.2% were of T3, T4a and T4b stage. Primary tumour macroscopic features included 41.1%, 12.6% and 23.7% with synchronous peritoneal involvement, perforated primary and ovarian metastases. Primary tumour microscopic features included 8.1%, 44.0% and 5.6% with signet ring, mucinous and both pathologies. Individually T4 status, macroscopic and microscopic features would have identified 65.6%, 56.8% and 46.5% of patients. Any high-risk factor would have identified 85.6%. CONCLUSION: Our study suggests that T4 stage, high risk macroscopic and high-risk microscopic features at time of primary diagnosis identifies the majority of CRC patients who later develop PM. This provides support for a selective second-look protocol in such patients to enable early identification and, potentially, 'prevention' of CRC PM. PMID- 26995115 TI - Therapeutic efficacy of percutaneous microwave coagulation versus liver resection for single hepatocellular carcinoma <=3 cm with Child-Pugh A cirrhosis. AB - AIMS: This study aimed to compare the therapeutic efficacy of liver resection (LR) and percutaneous microwave coagulation therapy (PMCT) for single hepatocellular carcinoma <=3 cm (HCC) in cirrhotic livers. METHODS: In this study, 190 patients with single HCC <=3 cm and Child-Pugh A cirrhosis were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 68 patients received PMCT. The therapeutic efficacy and complications were compared between the two procedures. RESULTS: There was no treatment-related hospital mortality in either group. Major complications were significantly more frequent in the LR group compared to the PMCT group (22.1% vs 5.9%, p = 0.004). The 1-, 3 , and 5-year OS rates for the LR group and PMCT group were 98.4%, 93.6%, 55.2% and 97.1%, 87.7%, 51%, respectively. There was no significant difference in OS rates between the LR group and PMCT group (p = 0.153). The 1-, 3-, and 5-year DFS rates were 96.7%, 70.5% and 43.7%, respectively, in the LR group, which were significantly higher compared to the PMCT group (92.6%, 50.5% and 26.3%, p = 0.006). Subgroup analyses revealed that HCC patients with portal hypertension (PH), OS and DFS were similar between the two groups. CONCLUSIONS: LR may provide better DFS and lower recurrence rates than PMCT for single HCC <=3 cm and Child Pugh A cirrhosis. For HCC patients with PH, PMCT may provide therapeutic effects that are similar to LR. PMID- 26995116 TI - Modified total meso-pancreatoduodenum excision with pancreaticoduodenectomy as a mesopancreatic plane surgery in borderline resectable pancreatic cancer. AB - BACKGROUND: A superior mesenteric artery (SMA)-first approach has been considered to be an efficient technique in pancreaticoduodenectomy when the SMA is a factor of borderline resectable pancreatic head cancer (BRPHC). However, this excellent procedure has limitations in terms of tumor resection with an intact coverage including the pancreatic tumor and the tumor-draining lymphovascular systems and the ability to achieve a complete regional lymphadenectomy. METHODS: A modified mesenteric plane procedure has been developed that provides improved regional lymphadenectomy and permits adjustment of the surgical approach, which is based on the direction of the tumor infiltration. RESULTS: Of 55 patients taken to surgery, 19 had peritoneal dissemination and/or liver metastasis at staging laparoscopy, and the procedure revealed tumor infiltration to the SMA and/or hepatic artery (HA) in 4 patients. Finally, 32 patients with BRPHC have undergone the procedure between April 2009 and June 2015. Twenty-four of 32 patients (75.0%) had negative resection margins, and the median number of lymph nodes harvested was 34. Lymph nodes around the SMA tested positive for metastasis in 13 patients (40.6%), and those around the HA tested positive for metastasis in 7 patients (21.9%). Complications occurred in 14 patients (43.7%), with no perioperative mortality. Overall survival rates were 65.3% at 1 year and 35.2% at 3 years. CONCLUSIONS: Short-term results with the procedure may encourage surgical management for BRPHC. PMID- 26995117 TI - Reisolation of Staphylococcus aureus from bovine milk following experimental inoculation is influenced by fat percentage and specific immunoglobulin G1 titer in milk. AB - The associations of management parameters, herd characteristics, and individual cow factors with bovine mastitis have been subject of many studies. The present study aimed to evaluate the association between milk composition parameters, including fat, protein, lactose, urea, and specific immunoglobulin levels, at the time of experimental bacterial inoculation of the mammary gland and subsequent shedding dynamics of Staphylococcus aureus. Sixty-eight cows were experimentally infected with S. aureus and closely monitored for 3 wk. Mixed model analyses were used to determine the influence of management and herd characteristics (farm and experimental group), individual cow factors (days in milk, milk yield, and quarter position), and a challenge-related parameter (inoculation dose) in combination with either the milk components fat, protein, lactose and urea, or the S. aureus-specific antibody isotype titers at the time of bacterial inoculation, on the number of S. aureus reisolated from milk after inoculation. A positive association was observed between the milk fat percentage and the number of S. aureus reisolated from quarter milk, and a negative relationship between the S. aureus-specific IgG1 titer in milk and the number of S. aureus. These findings should be considered in the development of a vaccine against S. aureus induced bovine mastitis. PMID- 26995118 TI - Short communication: Cinnamaldehyde taste preferences of weaned dairy heifers. AB - Within a dairy enterprise, one major cost is raising young calves. Optimizing the feeding programs of dairy calves is imperative for the sustainability and profitability of dairy operations. Essential oils appear to be natural alternatives to antibiotics and function similarly to ionophores. Supplemental antibiotic ionophores have been very successful in improving feed efficiency and rate of gain in calves, as well as decreasing disease incidences; however, calves may be developing resistance to ionophores and the use of antibiotics in animal feeds has been a major concern for consumers. No current research has examined the value or palatability of supplementing essential oils to dairy heifers. The purpose of this sequential elimination experiment was to evaluate the taste preferences of 6 weaned dairy heifers [approximately 3mo old; 95+/-10.8kg of body weight (BW)] provided with 0 (control), 1, 2, 3, or 4mg/kg of BW of cinnamaldehyde daily. Heifers had 2 d of adaptation to the new feeding regimen before the experiment started and were then offered the 5 experimental diets for 5 d. The most preferred diet was removed and the study continued with the 4 remaining diets. The most preferred diets were again eliminated sequentially, so that only 2 diets remained on d 13 and 14. Each diet was ranked based on the weight of feed refused at the end of each feeding segment. Overall ranking of the 5 treatments were control, 2, 1, 3, and 4mg/kg of BW of cinnamaldehyde. Results indicated that heifers preferred diets without cinnamaldehyde; however, when only cinnamaldehyde diets remained, dry matter intake was not negatively affected regardless of the concentration of cinnamaldehyde provided. PMID- 26995119 TI - Effects of dry period length and dietary energy source on milk yield, energy balance, and metabolic status of dairy cows over 2 consecutive years: Effects in the second year. AB - The objective of the current study was to evaluate the effect of dry period (DP) length on milk yield, energy balance (EB), and metabolic status in cows fed a lipogenic or glucogenic diet in the second year after implementation of DP and dietary treatments. Holstein-Friesian dairy cows (n=167) were assigned randomly to 1 of 3 DP lengths (0, 30, or 60d) and 1 of 2 early lactation diets (glucogenic or lipogenic) for 2 consecutive years. Results of the first year were reported previously. In the second year, 19 cows in the 0-d DP group were attributed to a new group (0->67d DP) because these cows had a milk yield of <4kg/d at least 30d before expected calving date and were dried off. Milk yield was recorded and EB was calculated from wk -8 to 9 relative to calving. Blood samples were taken weekly from wk -3 to 8 relative to calving. Liver samples were taken in wk -2, 2, and 4 relative to calving. At the onset of lactation, cows with a 0-d or 0->67-d DP had greater body condition score (BCS) than cows with a 60-d DP. During the first 9wk, cows with a 0- or 30-d DP produced 5.0 and 4.3kg less milk per day, respectively, but had similar EB compared with cows with a 60-d DP. Cows with a 0 or 30-d DP produced additional milk precalving, which could compensate milk yield losses in the first 9wk postcalving. Cows with a 0-d DP did not have milk yield losses or improve EB in the second year as much as in the first year. Cows with a 0-d DP had greater plasma insulin and insulin-like growth factor-I (IGF-I) and lower liver triacylglycerol concentrations than cows with other DP lengths. Cows with a 0->67-d DP had lower EB, and greater plasma free fatty acids (FFA) and beta-hydroxybutyrate (BHB) concentrations than cows with other DP lengths. Feeding a glucogenic diet increased plasma glucose, IGF-I, and insulin concentrations, and decreased plasma FFA, BHB, and urea concentrations compared with a lipogenic diet, independent of DP length. In conclusion, omitting the DP or feeding a glucogenic diet improved metabolic status in early lactation of the second year after implementation of DP length and dietary treatments, although effects of omitting the DP were less pronounced in the second year than in the first year. The less pronounced improvement of EB in the second year was related to the high BCS at the onset of lactation and reduced milk yield losses in cows with a 0-d DP. PMID- 26995120 TI - Factors influencing degree of glycosylation and phosphorylation of caseins in individual cow milk samples. AB - The aim of this study was to examine variations in posttranslational modifications (PTM) of caseins (CN) in milk from individual cows and determine how these differ between breeds, across lactation, and between variants. Furthermore, we examined the variation of casein PTM in relation to rennet coagulation properties of milk. In total, detailed protein composition of milk from 892 Danish Holstein and Jersey cows was determined by liquid chromatography/electrospray ionization-mass spectrometry. The method measured relative contents of the main milk proteins as well as several variants and PTM. The results showed that the 2 breeds had distinct milk protein composition. Milk from Danish Holstein cows was mainly characterized by higher relative contents of beta-CN, alpha-lactalbumin (alpha-LA), and beta-lactoglobulin, and a higher fraction of glycosylated kappa-CN (G kappa-CN), whereas milk from Danish Jersey cows was characterized by higher relative contents of kappa-CN, alphaS2-CN, and the less phosphorylated forms of alphaS1-CN and alphaS2-CN. Univariate linear models including days in milk and parity as class effects showed variation in the detailed protein profile across and between lactations; in particular, changes in the degree of glycosylation of kappa-CN were pronounced, but changes in alphaS1 CN 8P to total alphaS1-CN and alphaS2-CN 11P to alphaS2-CN were also observed over lactation for both breeds. The phosphorylated forms of alphaS1-CN and alphaS2-CN were, to some extent, correlated. Further, the kappa-CN BB genotype was associated with higher relative contents of both unglycosylated kappa-CN (UG kappa-CN) and G kappa-CN compared with kappa-CN AA; kappa-CN AB showed intermediate results in both breeds. The influence of protein composition on rennet coagulation properties was explored based on 4 classes for curd firming rate: noncoagulation, and poor, average, and good coagulation. The results revealed breed differences: Holstein milk, higher relative content of kappa-CN to total protein, and higher content of G kappa-CN were associated with improved milk coagulation. In contrast, relative content of alpha-LA was the main component associated with milk coagulation properties in Danish Jerseys and it was shown to affect milk coagulation properties negatively. In addition, variation in phosphorylation degrees of alphaS1-CN also played a role. This study demonstrates that although the genetic influence of glycosylation seems to be the same in both breeds, nongenetic variation differs, which is further reflected in different associations with milk coagulation properties. PMID- 26995121 TI - The effect of subclinical ketosis on activity at estrus and reproductive performance in dairy cattle. AB - Our aims were to investigate the influence of subclinical ketosis (SCK) on physical activity at estrus using a neck accelerometer device and on future reproductive performance. Two hundred three Holstein-Friesian cows were studied on 3dairy farms in Northwest England between September 2013 and March 2014. Seventeen percent (35 of 203) of the enrolled cows were affected with SCK between 7 and 21d in milk, defined as a blood beta-hydroxybutyrate concentration of 1.2 to 2.9mmol/L. Time to event analyses and multivariable regression analyses were used to assess the effect of SCK on reproductive performance and activity at estrus. The SCK cows exhibited a lower peak activity (measured as the number of standard deviations above mean activity) and shorter duration in activity clusters associated with first estrus and first insemination postpartum, compared with non-SCK cows. Peak activity and cluster duration associated with the insemination that led to a pregnancy were not different between SCK and non-SCK cows. Calving to first estrus, calving to first insemination, and calving to pregnancy intervals were prolonged in SCK cows. First insemination was 4.3 times (95% confidence interval=1.6 to 15.0) less likely to be successful in SCK cows compared with non-SCK cows. Adjusted mean number of inseminations per pregnancy was 2.8 for SCK cows and 2.0 for non-SCK cows. The current study confirms the long-lasting effects of SCK on reproductive efficiency. Furthermore, it is indicated that physical activity around estrus is reduced by SCK in early lactation, but this negative effect appears to diminish as cows progress through lactation. PMID- 26995122 TI - A comparison of individual cow versus group concentrate allocation strategies on dry matter intake, milk production, tissue changes, and fertility of Holstein Friesian cows offered a grass silage diet. AB - A diverse range of concentrate allocation strategies are adopted on dairy farms. The objectives of this study were to examine the effects on cow performance [dry matter (DM) intake (DMI), milk yield and composition, body tissue changes, and fertility] of adopting 2 contrasting concentrate allocation strategies over the first 140 d of lactation. Seventy-seven Holstein-Friesian dairy cows were allocated to 1 of 2 concentrate allocation strategies at calving, namely group or individual cow. Cows on the group strategy were offered a mixed ration comprising grass silage and concentrates in a 50:50 ratio on a DM basis. Cows on the individual cow strategy were offered a basal mixed ration comprising grass silage and concentrates (the latter included in the mix to achieve a mean intake of 6kg/cow per day), which was formulated to meet the cow's energy requirements for maintenance plus 24kg of milk/cow per day. Additional concentrates were offered via an out-of-parlor feeding system, with the amount offered adjusted weekly based on each individual cow's milk yield during the previous week. In addition, all cows received a small quantity of straw in the mixed ration part of the diet (approximately 0.3kg/cow per day), plus 0.5kg of concentrate twice daily in the milking parlor. Mean concentrate intakes over the study period were similar with each of the 2 allocation strategies (11.5 and 11.7kg of DM/cow per day for group and individual cow, respectively), although the pattern of intake with each treatment differed over time. Concentrate allocation strategy had no effect on either milk yield (39.3 and 38.0kg/d for group and individual cow, respectively), milk composition, or milk constituent yield. The milk yield response curves with each treatment were largely aligned with the concentrate DMI curves. Cows on the individual cow treatment had a greater range of concentrate DMI and milk yields than those on the group treatment. With the exception of a tendency for cows on the individual cow treatment to lose more body weight to nadir than cows on the group treatment, concentrate allocation strategy had little effect on either body weight or body condition score over the experimental period. Cows on the individual cow treatment had a higher pregnancy rate to first and second service and tended to have a higher 100-d in calf rate than cows on the group treatment. This study demonstrates that concentrate allocation strategy had little effect on overall production performance. PMID- 26995123 TI - The protein and lipid composition of the membrane of milk fat globules depends on their size. AB - In bovine milk, fat globules (MFG) have a heterogeneous size distribution with diameters ranging from 0.1 to 15 um. Although efforts have been made to explain differences in lipid composition, little is known about the protein composition of MFG membranes (MFGM) in different sizes of MFG. In this study, protein and lipid analyses were combined to study MFG formation and secretion. Two different sized MFG fractions (7.6+/-0.9 um and 3.3+/-1.2 um) were obtained by centrifugation. The protein composition of MFGM in the large and small MFG fractions was compared using mass-spectrometry-based proteomics techniques. The lipid composition and fatty acid composition of MFG was determined using HPLC evaporative light-scattering detector and gas chromatography, respectively. Two frequently studied proteins in lipid droplet biogenesis, perilipin-2 and TIP47, were increased in the large and small MFG fractions, respectively. In the large MFG fraction, besides perilipin-2, cytoplasmic vesicle proteins (heat shock proteins, 14-3-3 proteins, and Rabs), microfilaments and intermediate filament related proteins (actin and vimentin), host defense proteins (cathelicidins), and phosphatidylinositol were higher in concentration. On the other hand, cholesterol synthesis enzymes [lanosterol synthase and sterol-4-alpha-carboxylate 3 dehydrogenase (decarboxylating)], cholesterol, unsaturated fatty acids, and phosphatidylethanolamine were, besides TIP47, higher in concentration in the small MFG fraction. These results suggest that vesicle proteins, microfilaments and intermediate filaments, cholesterol, and specific phospholipids play an important role in lipid droplet growth, secretion, or both. The observations from this study clearly demonstrated the difference in protein and lipid composition between small and large MFG fractions. Studying the role of these components in more detail in future experiments may lead to a better understanding of fat globule formation and secretion. PMID- 26995124 TI - Shelf life of donkey milk subjected to different treatment and storage conditions. AB - The aim of this study was to investigate the effects of different treatment conditions on microbiological indicators of donkey milk hygiene and their evolution during shelf life at 4 and 12 degrees C from 3 to 30d, simulating a farm-scale pasteurization and packing system. Four treatment conditions were tested: no treatment (raw milk), pasteurization (65 degrees C * 30 min), high pressure processing (HPP), and pasteurization plus HPP. The microbiological quality of the raw donkey milk investigated was not optimal; our results highlight the importance of raw milk management with the need for animal hygiene management and good dairy farming practices on donkey farms to improve handling procedures. The raw milk treated with HPP alone showed visible alterations with flocks, making the milk unfit for sale. The microbiological risk posed by consumption of raw donkey milk was significantly reduced by heat treatment but farm-scale packing systems cannot guarantee an extended shelf life. In contrast, the pasteurization plus HPP treatment was the most effective method to maintain microbiological milk quality. Microflora growth had little effect on pH in donkey milk: pH values were significantly different only between raw milk and pasteurized and pasteurized plus HPP milk stored at 12 degrees C for 3d. Alkaline phosphatase activity and furosine could be used as indicators of proper pasteurization and thermal processing in donkey milk. Moreover, the presence and growth of Bacillus cereus in the case of thermal abuse hamper the wide-scale marketing of donkey milk due to the potential consequences for sensitive consumers and therefore further tests with time/temperature/high-pressure protocols associated with B. cereus are needed. Finally, our study shows that an HPP treatment of pasteurized milk after packing extends the shelf life of donkey milk and assures its microbial criteria up to 30d if properly stored at 4 degrees C until opening; therefore, combined heat treatment and storage strategies are recommended to enhance the shelf life of donkey milk. PMID- 26995125 TI - Physicochemical evaluation of sheep milk yogurts containing different levels of inulin. AB - The present study aimed to evaluate the physicochemical parameters of sheep milk yogurt smoothies (SMY) containing inulin at different levels (0, 2, 4, and 6%). Titratable acidity and pH, yogurt bacteria counts, fatty acids profile, and healthy lipid indices were evaluated during 28 d of refrigerated storage. As expected for yogurts, Streptococcus thermophilus counts decreased 1 to 3 log cycles and Lactobacillus delbrueckii ssp. bulgaricus counts decreased 1 to 2 cycles from d 1 to 28. The protective effect of inulin on bacteria survival and viability in the food matrix was not verified in the prebiotic SMY during storage, regardless of inulin level. Although lower post-acidification was observed in prebiotic SMY due to inulin addition, no changes were verified in short-chain fatty acids (SCFA) or polyunsaturated fatty acids (PUFA). In contrast, an increase in medium- and long-chain fatty acids (MCFA and LCFA) and monounsaturated fatty acids (MUFA) was observed during storage in all SMY. The most significant levels of fatty acids in SMY were oleic acid, followed by palmitic and myristic acids. A high positive correlation between conjugated linoleic acid (CLA) and oleic acid (r=0.978) was observed. The cis-9,trans-11 CLA isomer represented approximately 78% of total PUFA and 2% of total fatty acids, whereas alpha-linoleic acid comprised about 22% PUFA and 1% of total fatty acids in SMY. The fatty acid changes during storage were associated with the metabolic activity of the starter bacteria, especially for oleic acid and cis-9,trans-11 CLA isomer. Thus, the SMY represented a great source of these compounds. We observed that inulin levels did not affect fatty acids. A nonsignificant decrease in atherogenic index was observed during storage in all SMY, and a positive correlation (r=0.973) was found between atherogenic index and thrombogenic index of SMY. High correlations were observed between lauric and myristic acids and saturated fatty acids (r=0.907 and r=0.894, respectively), providing evidence of their atherogenic and thrombogenic potential. A negative correlation was observed between stearic acid and atherogenic index (r=-0.612) and between oleic acid and atherogenic index. Sheep milk yogurt could be characterized as a food with low atherogenic and thrombogenic risk because of its healthy lipid composition. Therefore, addition of inulin to SMY could be a good option to improve functionality of this food matrix for dairy companies wishing to enter the functional food market. PMID- 26995126 TI - Short communication: The effect of storage conditions over time on bovine colostral immunoglobulin G concentration, bacteria, and pH. AB - The objective of the present study was to measure the effect of storing colostrum in different conditions for varying amounts of time on IgG concentration, bacteria, and pH. In experiment 1, colostrum from 12 Holstein-Friesian cows (6 primiparous and 6 multiparous) was collected within 3h of calving, and colostrum from another 12 multiparous cows was collected within 3h of calving (6 cows) and >9h postpartum (6 cows). Aliquots were refrigerated or stored at room temperature for up to 72h, depending on treatment. In experiment 2, colostrum was collected from 6 multiparous cows within 9h of calving, and aliquots were stored for up to 72h in temperature-controlled units set at 4, 13, and 20 degrees C. All colostrum samples were analyzed for IgG concentration, total bacteria count, and pH after 0, 6, 12, 24, 36, 48, 60, and 72h of storage. Storage conditions did not affect the IgG concentration of colostrum. Bacterial growth was most rapid in the first 6h of storage, reducing thereafter, but bacteria multiplied at a significantly greater rate when stored in warmer conditions (i.e., >4 degrees C). The pH of colostrum was not significantly altered when stored at temperatures <13 degrees C, but when stored at 20 degrees C the pH significantly decreased after 24h of storage. Storing colostrum in warmer conditions significantly alters both total bacteria count and pH; consequently, colostrum should be stored at <=4 degrees C. PMID- 26995127 TI - Dairy farms testing positive for Mycobacterium avium ssp. paratuberculosis have poorer hygiene practices and are less cautious when purchasing cattle than test negative herds. AB - Mycobacterium avium ssp. paratuberculosis (MAP), the causative agent of Johne's disease, is present on most dairy farms in Alberta, causing economic losses and presenting a potential public health concern. The objective of this cross sectional study was to identify risk factors for Alberta dairy herds being MAP positive based on environmental samples (ES). Risk assessments were conducted and ES were collected on 354 Alberta dairy farms (62% of eligible producers) voluntarily participating in the Alberta Johne's Disease Initiative. In univariate logistic regression, risk factors addressing animal and pen hygiene, as well as the use of feeding equipment to remove manure and manure application on pastures, were all associated with the number of positive ES. Furthermore, based on factor analysis, risk factors were clustered and could be summarized as 4 independent factors: (1) animal, pen, and feeder contamination; (2) shared equipment and pasture contamination; (3) calf diet; and (4) cattle purchase. Using these factor scores as independent variables in multivariate logistic regression models, a 1-unit increase in animal, pen, and feeder contamination resulted in 1.31 times higher odds of having at least 1 positive ES. Furthermore, a 1-unit increase in cattle purchase also resulted in 1.31 times the odds of having at least 1 positive ES. Finally, a 100-cow increase in herd size resulted in an odds ratio of 2.1 for having at least 1 positive ES. In conclusion, cleanliness of animals, pens, and feeders, as well as cattle purchase practices, affected risk of herd infection with MAP. Therefore, improvements in those management practices should be the focus of effective tools to control MAP on dairy farms. PMID- 26995128 TI - Antibacterial and antiproliferative peptides in synbiotic yogurt-Release and stability during refrigerated storage. AB - The search for alternative therapeutics is on the rise due to the extensive increase in bacterial resistance to various conventional antibiotics and side effects of conventional cancer therapies. Bioactive peptides released from natural sources such as dairy foods by lactic acid bacteria have received attention as a potential source of biotherapeutic peptides. However, liberation of peptides in yogurt depends on proteolytic activities of the cultures used. Thus, this research was conducted to establish generation of inhibitory peptides in yogurt against pathogenic bacteria and cancer cells during storage at 4 degrees C for 28d. Water-soluble crude peptide extracts were prepared by high speed centrifugation of plain and probiotic yogurts supplemented with or without pineapple peel powder (PPP). The inhibition zones against Escherichia coli and Staphylococcus aureus by PPP-fortified probiotic yogurt at 28d of storage were, respectively, 25.89 and 11.72mm in diameter, significantly higher than that of nonsupplemented control yogurts. Antiproliferative activity against HT29 colon cancer cells was also significantly higher in probiotic yogurt with PPP than in nonsupplemented probiotic yogurt. Overall, crude water-soluble peptide extracts of the probiotic yogurt with PPP possessed stronger inhibitory activities against bacteria and cancer cells than controls, and these activities were maintained during storage. However, activities were lowered substantially during in vitro gastrointestinal digestion. These findings support the possibility of utilizing dairy-derived bioactive peptides in the development of a superior alternative to the current generation of antibacterial and anticancer agents, as well as a functional ingredient in foods, nutraceuticals, and pharmaceuticals. PMID- 26995129 TI - Effect of exchanging Onobrychis viciifolia and Lotus corniculatus for Medicago sativa on ruminal fermentation and nitrogen turnover in dairy cows. AB - The objective of the study was to determine the effect of feeding sainfoin (SF; Onobrychis viciifolia) and birdsfoot trefoil (BT; Lotus corniculatus), 2 temperate climate forage legumes that contain condensed tannins (CT), on ruminal fermentation and N turnover in dairy cows. Six ruminally cannulated multiparous dairy cows (milk yield=40kg/d; 36 d in milk) were used in a replicated 3*3 Latin square design. All animals were fed basal diets containing 20% pelleted SF (223g of CT/kg of dry matter), BT (30.3g of CT/kg of dry matter), or alfalfa (AL) and concentrate to meet their predicted nutrient requirements. Each experimental period consisted of a 21-d adaptation period in a tiestall, followed by a 7-d collection period in metabolic crates, where feces and urine were collected quantitatively. During the 7-d period, milk yield was recorded daily and milk samples were taken at each milking. Blood, ruminal fluid, and papillae were sampled on d 2 and 5. The relative abundance of selected bacterial strains in ruminal fluid and the gene expression of transporter genes in the papillae were determined with quantitative PCR. Total volatile fatty acids and the abundance of the cellulolytic bacteria Prevotella spp. and Ruminococcus flavefaciens decreased with SF compared with AL. The relative gene expression of the monocarboxylate transporter 1 was increased with BT compared with AL and SF. Total yields of milk, milk fat, and milk protein were similar among treatments. The proportion of 18:3n-3 in milk fat was greater and those of 22:5n-3 and 22:6n-3 were lower with SF than with BT. The contents of urea N in blood (2.71, 3.45, and 3.90mmol/L for SF, AL, and BT, respectively), milk (79.8, 100.1, and 110.9mg/kg for SF, AL, and BT, respectively), and urine were lower with SF than with AL and BT, and a trend toward a lower ruminal ammonia content occurred with SF compared with BT. Intake and excretion of N with milk were similar among treatments, but urine N was lower with SF than with AL. The N excretion to N intake relation showed a shift in a part of urine N (17.5, 20.8, and 19.5% for SF, AL, and BT, respectively) to fecal N (45.2, 41.3, and 38.5% for SF, AL, and BT respectively) with SF compared with AL and BT. In conclusion, SF and BT differed in their effects on fermentation and milk fatty acid profile and SF also showed potential to decrease metabolic and environmental loads. The main reason for the different efficiency was likely a higher CT content of SF compared with BT. PMID- 26995131 TI - Colostrum and milk pasteurization improve health status and decrease mortality in neonatal calves receiving appropriate colostrum ingestion. AB - The objective of the study was to evaluate if on-farm heat treatment of colostrum and bulk tank milk can improve calf health status and morbidity and mortality rates during the first 21d of life in neonatal Holstein calves receiving appropriate colostrum ingestion. A total of 587 calves were randomly assigned to 2 groups of males and females over 18mo. The nonpasteurized group (n=287, 143 males and 144 females) was fed frozen (-20 degrees C) colostrum (6-8L during the first 12h of life) that was previously reheated up to 40 degrees C. They were also fed refrigerated (4 degrees C) raw milk from the bulk tank that was also reheated up to 40 degrees C (1.8L every 12h). The pasteurized group (n=300, 150 males and 150 females) was also fed colostrum and milk, but both were pasteurized before freezing. Blood samples were drawn from all calves to obtain serum at 2 to 5d of life. Serum total protein (g/dL) was determined using a commercially available refractometer. Colostrum and milk underwent routine bacteriological analysis to determine total plate counts (cfu/mL) and total coliform counts (cfu/mL). All the calves underwent clinical examination every 24h during the first 21d of life. Every day, calves were clinically diagnosed either as being healthy or suffering from respiratory disease, neonatal calf diarrhea, or suffering other diseases. On-farm heat treatment for colostrum and milk reduced total plate counts and total coliform counts between 1 and 2 log10. Pasteurization of colostrum and milk significantly decreased the morbidity and mortality (5.2 and 2.8%) in comparison with calves receiving nonpasteurized colostrum and milk (15.0 and 6.5%), respectively, during the first 21d of life, even in animals receiving appropriate colostrum ingestion. PMID- 26995130 TI - Chromium propionate supplementation during the peripartum period interacts with starch source fed postpartum: Production responses during the immediate postpartum and carryover periods. AB - Forty-eight multiparous cows were used in a randomized complete block design experiment with a 2*2 factorial arrangement of treatments to determine the interaction between chromium propionate (CrPr) supplementation and sources of corn varying in ruminal starch fermentability on production responses during the postpartum (PP) and carryover periods. During the peripartum period (28d before expected parturition until 28d PP), diets were top-dressed (20g/d) with either CrPr (KemTRACE Chromium Propionate, Kemin Industries, Des Moines, IA; 8mg of Cr/cow per day) or control (Con; ground corn). At parturition, cows were randomly assigned to corn treatment within CrPr and Con treatments: dry corn (DC) or high moisture corn (HMC). Treatment combinations (CrPr/DC, CrPr/HMC, Con/DC, and Con/HMC) were fed from parturition until 28d PP (treatment period). Cows were fed a common diet to evaluate potential carryover effects of the treatment diets from 29 to 84d PP (carryover period). The CrPr and corn treatments interacted over time to affect yield of 3.5% fat-corrected milk (FCM) during both the treatment and carryover periods. The CrPr/HMC treatment combination tended to increase FCM compared with Con/DC and Con/HMC by 28d PP (57.4 vs. 48.6 and 48.5kg/d, respectively) and increased FCM compared with Con/DC by 42d PP (59.2 vs. 44.8kg/d). The CrPr tended to increase milk yield (55.4 vs. 51.9kg/d) regardless of corn source during the carryover period after treatment ceased. Daily and cumulative DMI were not affected by treatment during the PP period, but CrPr and corn treatments interacted over time to affect daily DMI during the carryover period; DMI was generally higher for CrPr/HMC, lower for Con/DC, and intermediate for CrPr/DC and Con/HMC from 29 to 84d PP. Supplementation of CrPr throughout the peripartum period interacted with starch source in PP diets over time to affect production responses that were sustained after treatment application ceased. PMID- 26995132 TI - Alternative haplotype construction methods for genomic evaluation. AB - Genomic evaluation methods today use single nucleotide polymorphism (SNP) as genomic markers to trace quantitative trait loci (QTL). Today most genomic prediction procedures use biallelic SNP markers. However, SNP can be combined into short, multiallelic haplotypes that can improve genomic prediction due to higher linkage disequilibrium between the haplotypes and the linked QTL. The aim of this study was to develop a method to identify the haplotypes, which can be expected to be superior in genomic evaluation, as compared with either SNP or other haplotypes of the same size. We first identified the SNP (termed as QTL SNP) from the bovine 50K SNP chip that had the largest effect on the analyzed trait. It was assumed that these SNP were not the causative mutations and they merely indicated the approximate location of the QTL. Haplotypes of 3, 4, or 5 SNP were selected from short genomic windows surrounding these markers to capture the effect of the QTL. Two methods described in this paper aim at selecting the most optimal haplotype for genomic evaluation. They assumed that if an allele has a high frequency, its allele effect can be accurately predicted. These methods were tested in a classical validation study using a dairy cattle population of 2,235 bulls with genotypes from the bovine 50K SNP chip and daughter yield deviations (DYD) on 5 dairy cattle production traits. Combining the SNP into haplotypes was beneficial with all tested haplotypes, leading to an average increase of 2% in terms of correlations between DYD and genomic breeding value estimates compared with the analysis when the same SNP were used individually. Compared with haplotypes built by merging the QTL-SNP with its flanking SNP, the haplotypes selected with the proposed criteria carried less under- and over represented alleles: the proportion of alleles with frequencies <1 or >40% decreased, on average, by 17.4 and 43.4%, respectively. The correlations between DYD and genomic breeding value estimates increased by 0.7 to 0.9 percentage points when the haplotypes were selected using any of the proposed methods compared with using the haplotypes built from the QTL-SNP and its flanking markers. We showed that the efficiency of genomic prediction could be improved at no extra costs, only by selecting the proper markers or combinations of markers for genomic prediction. One of the presented approaches was implemented in the new genomic evaluation procedure applied in dairy cattle in France in April 2015. PMID- 26995133 TI - Production, composition, and oxidative stability of milk highly enriched in polyunsaturated fatty acids from dairy cows fed alfalfa protein concentrate or supplemental vitamin E. AB - Given its elevated content of carotenoids, alfalfa protein concentrates (APC) have the potential to prevent oxidation of milk enriched in polyunsaturated fatty acids. The effects of feeding APC or supplemental vitamin E on production, composition, and oxidative stability of milk enriched in polyunsaturated fatty acids were evaluated using 6 lactating Holstein cows (224+/-18d in milk) in a replicated 3*3 Latin square (21-d periods, 14d for adaptation). Treatment diets contained (dry matter basis) (1) 9% soybean meal (control, CTL); (2) 9% soybean meal + 300 IU of vitamin E/kg (VitE treatment); or (3) 9% APC (APC treatment). Cows received a continuous abomasal infusion of 450g/d of linseed oil. As a result, milk fat content of cis-9,cis-12 18:2 increased from 1.08+/-0.13 to 3.9+/ 0.40% (mean +/- SD), whereas cis-9,cis-12,cis-15 18:3 increased from 0.40+/-0.04 to 14.27+/-1.81% during the experimental period compared with the pretrial period. Milk yield tended to be higher for APC (14.7kg/d) compared with CTL (13.4kg/d), and was greater than that for VitE (13.0kg/d). Protein yield was higher in cows fed APC (518g/d) compared with VitE (445g/d) but was not different from that in cows fed CTL (483g/d). These effects resulted in improved milk N efficiency in cows fed APC (26.1% of N intake secreted in milk) compared with CTL (23.0%) and VitE (22.9%). Feeding APC increased milk fat content of lutein (252MUg/g) compared with CTL (204MUg/g) and VitE (190MUg/g). Milk fat content of vitamin E was higher for APC (34.5MUg/g) compared with CTL (19.0MUg/g) and tended to be lower than that with VitE (44.9MUg/g). Redox potential of fresh milk from cows fed APC (152mV) was similar to that of VitE (144mV), but lower than that of CTL (189mV). Treatments had no effect on fresh milk contents of dissolved oxygen (8.1+/-1.5mg/L), and conjugated diene hydroperoxides (2.7+/-0.5mmol/L). The concentrations of volatile lipid oxidation products (propanal, hexanal, hept-cis 4-enal, 1-octen-3-one) tended to be decreased by APC relative to CTL, whereas similar values were observed for VitE, except for hexanal, which was reduced by 40% in VitE. In conclusion, feeding APC to lactating dairy cows could serve as a source of dietary protein that improves dietary N utilization efficiency, and also as a preharvest technology to increase natural antioxidant levels in milk to limit oxidation. PMID- 26995134 TI - Short communication: Altered expression of specificity protein 1 impairs milk fat synthesis in goat mammary epithelial cells. AB - Specificity protein 1 (encoded by SP1) is a novel transcription factor important for the regulation of lipid metabolism and the normal function of various hormones in model organisms. Its potential role, if any, on ruminant milk fat is unknown. Despite the lower expression of the lipolysis-related gene ATGL (by 44 and 37% respectively), both the adenoviral overexpression and the silencing of SP1 [via short interfering (si)RNA] markedly reduced cellular triacylglycerol (TAG) content (by 28 and 25%, respectively), at least in part by decreasing the expression of DGAT1 (-36% in adenovirus treatment) and DGAT2 (-81 and -87%, respectively) that are involved in TAG synthesis. Consistent with the markedly lower expression of genes related to lipid droplet formation and secretion (TIP47 by 19 and 32%, and ADFP by 25 and 25%, respectively), cellular lipid droplet content was also decreased sharply, by 9 and 8.5%, respectively, after adenoviral overexpression of SP1 or its silencing via siRNA. Overall, the results underscored a potentially important role of SP1 in maintaining milk-fat droplet synthesis in goat mammary epithelial cells. PMID- 26995135 TI - Growth and acid production of Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 in the fermentation of algal carcass. AB - Algal carcass is a low-value byproduct of algae after its conversion to biodiesel. Dried algal carcass is rich in protein, carbohydrate, and multiple amino acids, and it is typically well suited for growth and acid production of lactic acid bacteria. In this study, Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 was used to ferment different algal carcass media (ACM), including 2% ACM, 2% ACM with 1.9% glucose (ACM-G), and 2% ACM with 1.9% glucose and 2g/L amino acid mixture (ACM-GA). Concentrations of organic acids (lactic acid and acetic acid), acetyl-CoA, and ATP were analyzed by HPLC, and activities of lactate dehydrogenase (LDH), acetokinase (ACK), pyruvate kinase (PK), and phosphofructokinase (PFK) were determined by using a chemical approach. The growth of L. bulgaricus cells in ACM-GA was close to that in the control medium (de Man, Rogosa, and Sharpe). Lactic acid and acetic acid contents were greatly reduced when L. bulgaricus cells were grown in ACM compared with the control medium. Acetyl-CoA content varied with organic acid content and was increased in cells grown in different ACM compared with the control medium. The ATP content of L. bulgaricus cells in ACM was reduced compared with that of cells grown in the control medium. Activities of PFK and ACK of L. bulgaricus cells grown in ACM were higher and those of PK and LDH were lower compared with the control. Thus, ACM rich in nutrients may serve as an excellent substrate for growth by lactic acid bacteria, and addition of appropriate amounts of glucose and amino acids can improve growth and acid production. PMID- 26995136 TI - Gas production and starch degradability of corn and barley meals differing in mean particle size. AB - The objective of this study was to verify the effect of mean particle size (mPS) on both gas production and in vitro rumen starch degradability (IVSD) of corn and barley meals (Cm and Bm, respectively). Batches of the same Cm or Bm were separately processed through 2 different mills (i.e., a cutter mill or a rotor speed mill) equipped with or without different screens to achieve different mPS for each tested meal. Samples were analyzed accordingly to a completely randomized design and the main tested effect of model was mPS (n=11, from 0.46 to 3.50mm mPS for Cm or n=10, from 0.11 to 2.98mm mPS for Bm). For both in vitro assays, the rumen inocula were collected from 2 rumen-fistulated Holstein lactating dairy cows fed a total mixed ration with 16.2% crude protein, 28.5% starch, and 35.0% neutral detergent fiber on a dry matter basis. To fit gas production data, 1-pool exponential model and 1-pool or 2-pool Gompertz models were adopted. The rate of gas production decreased and lag increased by increasing mPS of both Cm and Bm, irrespective of adopted 1-pool models. When the 2-pool Gompertz model was used to fit gas production data, a shift of particles from fast to slow fermentable pools was measured by increasing mPS. In particular, the ratio between fast and slow final volumes ranged from 0.90 at 0.11mm mPS to 0.10 at 2.98mm mPS for Bm. For Cm, the ratio between fast and slow final volumes decreased quadratically by increasing mPS, with the highest value (i.e., 0.58) measured at the lowest tested mPS. Values lower than 0.10 were measured for mPS greater than 1.93mm for Cm. Concerning IVSD data, linear decreases in rate of starch degradation equal to -0.049 or -0.092h(-1) for each 1 mm increase in mPS were achieved for Cm and Bm, respectively. The 7-h IVSD decreased by 6.3 or 6.5% starch for each 1-mm increase in mPS of Cm or Bm, respectively. Present findings supported the hypothesis that different particle sizes within the same starch source represent an important factor influencing both fermentation kinetic parameters and IVSD. PMID- 26995137 TI - Short communication: Individual cow variation in urinary excretion of phosphorus. AB - Some dairy cows excrete large amounts of P through their urine; thus, it was speculated that a genetic defect related to their efficiency in uptake of P or recirculation of P could cause such an effect. This speculation was pursued in a cross sectional study on 139 cows (103 Holstein and 36 Jersey) from an experimental herd using repeated sampling of urine (301 samples) to investigate sources of variation in urinary P concentration (Pu). Urine samples were taken on 6 testing sessions spread over 2 mo. Each sample was obtained by mild manual stimulation of the rear udder escutcheon area. The samples were immediately assayed for pH, stored frozen, and assayed for inorganic P and creatinine. Concentrations of P and creatinine in urine, the ratio of Pu to creatinine, and pH were analyzed using a linear mixed model. The model included fixed effects of breed, parity number, and sampling session. Stage of lactation was fitted as Wilmink-type lactation curves. Random effects included additive polygenic ancestry, permanent animal effects, and residual. The distribution of Pu approximated normality except for a single sample with very high Pu and very low pH. This sample came from a cow diagnosed independently with ketosis. For the remaining samples, it was shown that Pu has low to moderate heritability (0.12) and is only moderately repeatable (0.21). Based on a small data set, it is tentatively concluded that individual differences between cows exist in their Pu, and individual differences presumably result from genetic differences. However, it remains unclear if cows with genetically lower or higher Pu will perform better on a low-P diet. PMID- 26995138 TI - Short communication: Telomere lengths in different tissues of dairy cows during early and late lactation. AB - Telomeres create a protective cap on the ends of chromosomes that shorten with cell division and are influenced by stressful conditions. With the onset of lactation, high-yielding dairy cows are exposed to metabolic stress. In the present study, we aimed to analyze telomere length (TL) in key metabolic organs, such as liver, subcutaneous (sc) adipose tissue (AT), and mammary gland, as well as in peripheral blood cells during early and late lactation in German Holstein cows (n=21). Animals were fed according to their requirement, and biopsies from scAT, liver, and mammary gland as well as blood cells were collected in early and late lactation. The relative quantity of telomere products (qT), which is proportional to the average TL, was determined in genomic DNA by multiplex quantitative PCR. In this study, relative qT varied widely in the investigated tissues and blood. In late lactation, slowly proliferating tissues, such as liver and scAT, had the highest qT, whereas peripheral blood cells and in the mammary gland had the lowest qT. Comparing early with late lactation, relative qT attrition was limited to blood and mammary gland. Relationships between relative qT in blood, mammary gland, scAT, and liver suggest that blood qT might serve as a surrogate marker for tissue-specific qT. Cows with high initial qT in tissues and blood in early lactation had greater qT attrition during the course of lactation than cows with lower qT. The determination of qT could be included when phenotyping dairy cattle to test for associations with performance and fitness traits. PMID- 26995139 TI - Extracellular thermostable proteolytic activity of the milk spoilage bacterium Pseudomonas fluorescens PS19 on bovine caseins. AB - We studied the thermostable proteolytic activity of Pseudomonas fluorescens PS19 isolated from raw bovine milk. The heat-treated cell-free supernatant (HT-CFS) contained a thermostable protease of approximately 45 kDa, as revealed by casein zymography. We assigned this enzyme to P. fluorescens AprX metalloprotease (UniProtKB Acc. No. C9WKP6). After concentration by ultrafiltration at 10 kDa, the HT-CFS showed 2 other thermostable proteolytic bands on zymogram, with molecular masses of approximately 15 and 25 kDa. The former resulted a fragment of the AprX protease, whereas the 25-kDa protease was not homologous to any known protein of Pseudomonas spp. Subsequently, we assessed the proteolytic activity of the HT-CFS on bovine alphaS-, beta-, and kappa-casein during in vitro incubation at 7 or 22 degrees C. By means of ultra-performance liquid chromatography-tandem mass spectrometry we identified the released peptides (n=591). Some of them resisted proteolysis during the whole incubation period at both incubation temperatures and, therefore, they could be assumed as indicators of the proteolytic action of P. fluorescens PS19 on bovine caseins. PMID- 26995140 TI - Effects of candidate gene polymorphisms on the detailed fatty acids profile determined by gas chromatography in bovine milk. AB - Association analyses between candidate genes and bovine milk fatty acids can improve our understanding of genetic variation in milk fatty acid profiles and reveal potential opportunities to tailor milk fat composition through selection strategies. In this work, we investigated the association of 51 single nucleotide polymorphisms (SNP) selected from 37 candidate genes using a functional and positional approach, with 47 fatty acids, 9 fatty acid groups, and 5 Delta(9) desaturation indices in milk samples from Brown Swiss cows. Individual milk samples were collected from 1,158 Italian Brown Swiss cows, and gas chromatography was used to obtain detailed milk fatty acid compositions. A GoldenGate assay system (Illumina, San Diego, CA) was used to perform genotype 96 selected SNP located in 54 genes across 22 chromosomes. In total, 51 polymorphic SNP in 37 candidate genes were retained for the association analysis. A Bayesian linear animal model was used to estimate the contribution of each SNP. A total of 129 tests indicated relevant additive effects between a given SNP and a single fatty acid trait; 38 SNP belonging to 30 genes were relevant for a total of 57 fatty acid traits. Most of the studied fatty acid traits (~81%) were relevantly associated with multiple SNP. Relevantly associated SNP were mainly found in genes related to fat metabolism, linked to or contained in previously identified quantitative trait loci for fat yield or content, or associated with genes previously identified in association analyses with milk fatty acid profiles in other cow breeds. The most representative candidate genes were LEP, PRL, STAT5A, CCL3, ACACA, GHR, ADRB2, LPIN1, STAT1, FABP4, and CSN2. In particular, relevant associations with SNP located on bovine chromosome 19 (BTA19) were found. Two candidate genes on BTA19 (CCL3 and ACACA) were relevantly associated with de novo short- and medium-chain fatty acids, likely explaining the high heritability values found for these fatty acids (with the exception of C6:0). Two additional genes on BTA19 (CCL2 and GH1) showed associations with saturated and branched chain fatty acids. Our findings provide basic information on genes and SNP affecting the milk fatty acid composition of dairy cows. These results may support the possibility of using genetic selection to modify milk fatty acid profiles to promote beneficial health-related effects. PMID- 26995141 TI - Screening probiotic strains for safety: Evaluation of virulence and antimicrobial susceptibility of enterococci from healthy Chinese infants. AB - The aim of this study was to evaluate the safety of enterococci isolated from Chinese infants and screen out potential probiotic candidates. One hundred eight strains were isolated from feces of 34 healthy infants, and 38 strains of Enterococcus spp. were categorized as follows: E. faecalis (22), E. faecium (10), E. hirae (3), E. durans (2), and E. casseliflavus (1). Of these, 72.7% of E. faecalis came from infants delivered by cesarean and 62.5% of E. faecium from infants delivered vaginally. For safety evaluation of strains, we determined presence of virulence genes; production of hemolysin, gelatinase, and biofilm; and antimicrobial susceptibility of enterococci. Six out of 14 virulence genes were detected with a distribution of gelE (26.3%), cylA (39.4%), esp (15.8%), efaA (63.2%), asa1 (50.0%), and ace (50.0%). In phenotype analysis, 36.8% of the strains exhibited positive hemolytic activity and 17.5% were positive for production of gelatinase. Results of antimicrobial susceptibility showed that different percentages of the strains were resistant to ciprofloxacin (5.2%), vancomycin (7.8%), rifampicin (10.5%), erythromycin (52.6%), and gentamycin (52.6%); remarkably, none of the strains were resistant to ampicillin or chloramphenicol. In total, 10 strains, including 6 E. faecium, which are free of virulence determinants and sensitive to common antimicrobial agents (e.g., ampicillin and vancomycin), were further assessed for their probiotic properties. All strains survived well in simulated gastric fluid and intestinal tract, with maximum reductions of 0.600 and 0.887 log cfu/mL, respectively. Six strains of E. faecium could resist 0.3 to 1.0% bile salt, of which E. faecium WEFA23 presented the highest growth (75.06%) at 1.0% bile salt. All strains showed bile salt hydrolase activity on glycodeoxycholic acid, but only 3 of E. faecium showed activity on taurodeoxycholic acid. These results deliver useful information on the safety of enterococci in infants in China, and provide a protocol to screen probiotics for absence of virulence and antimicrobial susceptibility of enterococci. PMID- 26995142 TI - Optimization and validation of an existing, surgical and robust dry eye rat model for the evaluation of therapeutic compounds. AB - The aim of this research was to optimize and validate an animal model for dry eye, adopting clinically relevant evaluation parameters. Dry eye was induced in female Wistar rats by surgical removal of the exorbital lacrimal gland. The clinical manifestations of dry eye were evaluated by tear volume measurements, corneal fluorescein staining, cytokine measurements in tear fluid, MMP-9 mRNA expression and CD3(+) cell infiltration in the conjunctiva. The animal model was validated by treatment with Restasis((r)) (4 weeks) and commercial dexamethasone eye drops (2 weeks). Removal of the exorbital lacrimal gland resulted in 50% decrease in tear volume and a gradual increase in corneal fluorescein staining. Elevated levels of TNF-alpha and IL-1alpha have been registered in tear fluid together with an increase in CD3(+) cells in the palpebral conjunctiva when compared to control animals. Additionally, an increase in MMP-9 mRNA expression was recorded in conjunctival tissue. Reference treatment with Restasis((r)) and dexamethasone eye drops had a positive effect on all evaluation parameters, except on tear volume. This rat dry eye model was validated extensively and judged appropriate for the evaluation of novel compounds and therapeutic preparations for dry eye disease. PMID- 26995143 TI - Inactivation of p53 in pterygium influence miR-200a expression resulting in ZEB1/ZEB2 up-regulation and EMT processing. AB - Loss of p53 function has been linked to progression of pterygium. MiR-200a is known to be controlled by p53. Here, we hypothesize that expression of miR-200a and downstream ZEB1/ZEB2 genes are regulated epithelial-mesenchymal transition (EMT) involved in the pathogenesis and recurrence of pterygium. For this study, 120 primary pterygial samples were collected. Immunohistochemistry and real-time RT-PCR were performed to determine the expression of p53, p53 down-stream EMT associated protein and miR-200a. The molecular correlation of p53, miR-200a and downstream genes were confirmed using primary pterygium cells (PECs). Expression of miR-200a in pterygium tissues was significantly lower than in conjunctiva controls (p = 0.015). Up-regulated miR-200a levels were positively correlated with and p53 protein expression (p < 0.001). The miR-200a downstream ZEB1/ZEB1 protein expression were negative correlated with miR-200a expression. Cell model studies demonstrated that miR-200a controlled the EMT of PECs through up regulated ZEB1, ZEB2 and Snail gene expression. Our study demonstrated that inactivation of p53 in pterygium may influence miR-200a, resulting in ZEB1/ZEB2 up-regulation and EMT processing of pterygium. Therefore, we suggest that expression of miR-200a play an important role in EMT processing and recurrence of pterygium. PMID- 26995145 TI - The NPC2 protein: A novel dog allergen. AB - BACKGROUND: Dogs are an important source of indoor allergens that cause rhinoconjunctivitis, urticaria, and asthma in sensitized individuals. Can f 1 is reported as a major dog allergen, but other allergens have also been identified. Identification of immunologically important allergens is important for both the diagnosis and treatment of dog allergy. OBJECTIVE: To identify and characterize the canine NPC2 protein, a novel dog allergen. METHODS: We screened commercial and laboratory-generated aqueous dog extracts by 2-dimensional polyacrylamide gel electrophoresis with IgE immunoblotting using human serum samples from 71 dog allergic individuals. A target of interest was excised from the gel and sequenced. Canine NPC2 sequence was generated, and recombinant proteins expressed in yeast and bacteria were used to determine allergenicity. An IgE enzyme-linked immunosorbent assay was used for screening 71 dog-positive and 30 dog-negative serum samples. RESULTS: A 16-kDa protein (pK = 8.5) in dog allergen extracts was recognized by specific IgE. The protein was identified by sequencing as a CE1 protein or NPC2 protein. Human IgE bound to recombinant protein was expressed in both yeast and bacteria. Ten (14%) of 71 individuals had specific IgE to NPC2 protein from bacteria, and 12 (17%) had IgE to NPC2 protein from yeast. Binding of pooled dog-allergic serum IgE to the dust mite protein Der p 2 was partially inhibited by recombinant NPC2 protein. CONCLUSION: NPC2 protein, a member of the MD-2-related lipid recognition family, is identified as a dog allergen (Can f 7), with an apparent seroprevalence of 10% to 20%. PMID- 26995144 TI - Genetic analysis of consanguineous families presenting with congenital ocular defects. AB - Anophthalmia and microphthalmia (A/M) are a group of rare developmental disorders that affect the size of the ocular globe. A/M may present as the sole clinical feature, but are also frequently found in a variety of syndromes. A/M is genetically heterogeneous and can be caused by chromosomal aberrations, copy number variations and single gene mutations. To date, A/M has been caused by mutations in at least 20 genes that show different modes of inheritance. In this study, we enrolled eight consanguineous families with A/M, including seven from Pakistan and one from India. Sanger and exome sequencing of DNA samples from these families identified three novel mutations including two mutations in the Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) gene, [c.1310_1311delAT; p.(Tyr437Trpfs*44) and c.964G > A; p.(Val322Met)] and a single missense mutation in Forkhead Box E3 (FOXE3) gene, [c.289A > G p.(Ile97Val)]. Additionally two previously reported mutations were identified in FOXE3 and in Visual System Homeobox 2 (VSX2). This is the first comprehensive study on families with A/M from the Indian subcontinent which provides further evidence for the involvement of known genes with novel and recurrent mutations. PMID- 26995146 TI - Association of adiponectin and resistin gene polymorphisms in South Indian women with polycystic ovary syndrome. AB - OBJECTIVES: To investigate whether genetic polymorphisms in the resistin and adiponectin genes cause a predisposition towards polycystic ovary syndrome (PCOS) in a South Indian women population. STUDY DESIGN: This case controlled study included samples from 484 study subjects (282 diagnosed with PCOS and 200 normal controls). The clinical and biochemical parameters of the samples assayed included BMI, LH, FSH, testosterone, fasting glucose, adiponectin and resistin levels. Three single nucleotide polymorphisms of the resistin (RETN) gene 420(C >G) (rs1862513), 299(G->A) (rs3745367), and 62(G->A) (rs3745368), and two single nucleotide polymorphisms of the adiponectin (ADPIOQ) gene 45(T->G) (rs2241766), and 276(G->T) (rs1501299), were analyzed using a PCR-RFLP method. Statistical analysis was carried out to determine the association of the genotypic and allelic variations with the syndrome and also analyze the influence of genotypic variations on adipokine levels. RESULTS: Serum levels of testosterone, LH, fasting glucose and resistin were found to be significantly increased in the PCOS patients when compared to controls, while adiponectin was found to be significantly lower (P<0.05). BMI was found to positively correlate with resistin levels and negatively correlate with adiponectin levels. A positive association was found between the RETN promoter 420 (C->G) SNP and the intron 2 299 (G->A) variant of the resistin gene, while no association was found between the ADPIOQ gene polymorphisms and PCOS. The 'GG' variant of the adiponectin 45 (T->G) variant showed a near-significant tendency towards a decreased concentration of adiponectin in PCOS patients. CONCLUSIONS: Polymorphisms of the resistin gene could be assigned to play a role in increasing the risk of PCOS. However, the adiponectin gene does not seem to play a major role in PCOS susceptibility in a South Indian population. Serum adiponectin and resistin levels were more dependent on BMI rather than the presentation of PCOS. Obesity plays a major role in aggravating the hormonal disturbances found associated with PCOS. PMID- 26995147 TI - Initial clinical experience with a misoprostol vaginal insert in comparison with a dinoprostone insert for inducing labor. AB - OBJECTIVE: Only one phase III trial has been published to date on the efficacy and safety of misoprostol vaginal inserts for inducing labor. The aim of this study was to compare misoprostol inserts with dinoprostone inserts. STUDY DESIGN: This retrospective cohort study evaluated the reduction in time to vaginal delivery and delivery within 24h, in routine clinical work, in 119 labor inductions using a 200-MUg misoprostol vaginal insert (Misodel((r)); June-October 2014) in comparison with 124 inductions using a 10-mg dinoprostone insert (Propess((r)); December 2013-April 2014). RESULTS: Vaginal delivery within 24h occurred in 77.3% (n=92) of the misoprostol cohort and 74.2% (n=92) of the dinoprostone cohort (P=0.654). Time from insert application to vaginal delivery (min) was 761.76 (+/-409.44, cohort M) versus 805.17 (+/-473.00, cohort D) (P=0.817). Cesarean delivery was performed in 10.1% (n=12) versus 10.5% (n=13) in the misoprostol and dinoprostone cohorts, respectively (P>=0.999). The modified Bishop scores were 2.0 versus 3.0 (P=0.001), mean body mass index (BMI) was 24.72 versus 23.95 (P=0.033), and fetal scalp blood testing was required in 12.6% (n=15) versus 3.2% (n=4; P=0.008). No differences were observed with regard to the rates of transfer to the neonatal unit or any type of fetal acidosis. CONCLUSIONS: The groups thus had similar results for rates of vaginal delivery within 24h, cesarean delivery and fetal outcomes. The misoprostol group had lower modified Bishop scores, higher BMIs, and a higher rate of fetal scalp blood testing. PMID- 26995148 TI - Eremophilane sesquiterpenes from Hawaiian endophytic fungus Chaetoconis sp. FT087. AB - Seven sesquiterpene derivatives, including chaetopenoids A-F and dendryphiellin A1, and 6-methyl-(2E, 4E, 6S) octadienoic acid were isolated from the culture broth of Chaetoconis sp. FT087. Their structures were determined through the analysis of HRMS and NMR spectroscopic data. The absolute configurations of chaetopenoids A-D were elucidated by comparison of their CD and optical rotation data with those in the literature. Chaetopenoids A-C and E belong to the eremophilane type of sesquiterpenoids, while chaetopenoids D and F and dendryphiellin A1 have a trinor-eremophilane skeleton. All compounds were tested against A2780 and cisplatin resistant A2780CisR cell lines, and dendryphiellin A1 was moderately active with IC50 values of 6.6 and 9.1 MUg/mL, respectively. PMID- 26995149 TI - Prenylfuranocoumarin-HMGA-flavonol glucoside conjugates and other constituents of the fruit peels of Citrus hystrix and their anticholinesterase activity. AB - Sixteen compounds including dihydroxy prenylfuranocoumarins/3-hydroxy-3 methylglutaric acid conjugates and dihydroxy prenylfuranocoumarins/3-hydroxy-3 methylglutaric acid/1-O-flavonyl-beta-d-glucopyranoside conjugates, together with other dihydroxyprenylfuranocoumarins conjugates, were isolated from the ethyl acetate extract of the fruit peels of Citrus hystrix. Some of the isolates were evaluated for their cholinesterase inhibitory activity, but only one compound possessing a 3-O-beta-d-glucopyranosyl-3,5,7,4'-tetrahydroxy-6,8,3' trimethoxyflavonol nucleus in the prenylfuranocoumarin-HMGA conjugate showed strong activity. PMID- 26995150 TI - [Slowing down the flow of facial information enhances facial scanning in children with autism spectrum disorders: A pilot eye tracking study]. AB - OBJECTIVE: Face and gaze avoidance are among the most characteristic and salient symptoms of autism spectrum disorders (ASD). Studies using eye tracking highlighted early and lifelong ASD-specific abnormalities in attention to face such as decreased attention to internal facial features. These specificities could be partly explained by disorders in the perception and integration of rapid and complex information such as that conveyed by facial movements and more broadly by biological and physical environment. Therefore, we wish to test whether slowing down facial dynamics may improve the way children with ASD attend to a face. METHODS: We used an eye tracking method to examine gaze patterns of children with ASD aged 3 to 8 (n=23) and TD controls (n=29) while viewing the face of a speaker telling a story. The story was divided into 6 sequences that were randomly displayed at 3 different speeds, i.e. a real-time speed (RT), a slow speed (S70=70% of RT speed), a very slow speed (S50=50% of RT speed). S70 and S50 were displayed thanks to software called LogiralTM, aimed at slowing down visual and auditory stimuli simultaneously and without tone distortion. The visual scene was divided into four regions of interest (ROI): eyes region; mouth region; whole face region; outside the face region. The total time, number and mean duration of visual fixations on the whole visual scene and the four ROI were measured between and within the two groups. RESULTS: Compared to TD children, children with ASD spent significantly less time attending to the visual scenes and, when they looked at the scene, they spent less time scanning the speaker's face in general and her mouth in particular, and more time looking outside facial area. Within the ASD group mean duration of fixation increased on the whole scene and particularly on the mouth area, in R50 compared to RT. Children with mild autism spent more time looking at the face than the two other groups of ASD children, and spent more time attending to the face and mouth as well as longer mean duration of visual fixation on mouth and eyes, at slow speeds (S50 and/or S70) than at RT one. CONCLUSIONS: Slowing down facial dynamics enhances looking time on face, and particularly on mouth and/or eyes, in a group of 23 children with ASD and particularly in a small subgroup with mild autism. Given the crucial role of reading the eyes for emotional processing and that of lip-reading for language processing, our present result and other converging ones could pave the way for novel socio-emotional and verbal rehabilitation methods for autistic population. Further studies should investigate whether increased attention to face and particularly eyes and mouth is correlated to emotional/social and/or verbal/language improvements. PMID- 26995151 TI - [MODen: Psychoeducationnal therapeutic group program for schizophrenic patients, based on nutritional balance and pleasure, using cognitive functions: A pilot study]. AB - INTRODUCTION: Schizophrenia causes psychological difficulties (with positive and/or negative symptoms) as well as cognitive disabilities (attention, memory, executive functions and social cognition). Moreover, 40 to 60% of patients suffer from an excess of weight or obesity (due to bad eating habits, eating disorders or medication). All these difficulties impair their autonomy and their insertion into the society. In this context, setting-up a therapeutic tool, which may have cognitive benefits seems relevant. Thus, MODen is a therapeutic educational tool whose aim is to improve cognitive functions and the symptoms by using "nutritional balance" as an aid. METHOD: In this treatment program, two therapists lead a group of 5 to 8 patients which group meets once a week during two to four hours for 16 weeks, divided in 4 cycles. The first three weeks of each cycle consists of theoretical instruction: patients talk about their eating habits, information is given about nutritional balance and preparation of meals. In the different cycles, flexibility, planning, memory and attention are trained. For instance, the work on categorisation of foods and nutritional balance allow enhancing flexibility abilities. Writing down the lists of different ingredients needed for one week's meals and preparation of meals train planning abilities. MODen also takes into account ecological issues such as the limited budget of patients to do their shopping (this budget is around 4 euros per meal in France). The budget is also linked to planning abilities and reasoning. Finally, during the last session of each cycle the group prepares a meal (from the shopping to cooking). This last session is all about sharing and social cognition abilities. By the end of the program, patients will have prepared four meals together. Also "homework" has to be done each week in order to facilitate memorisation of what has been learned during the last session and to prepare the beginning of the next session. RESULTS: In a pilot study with 8 patients with schizophrenia (DSM-IV), improvements in PANSS negative symptoms and disorganization (respectively P<0.02; P<0.02) were observed. An underlying improvement at BECS scores was also observed (P<0.08). Regarding those preliminary results as well as the ecological qualities of this program, this therapeutic tool could be relevant in the treatment of patients with schizophrenia. PMID- 26995152 TI - [Affective mentalizing in Addictive Borderline Personality: A literature review]. AB - This literature review concerns affective mentalizing in borderline addictive personality. This concept postulates the group between addictions and borderline personalities may correspond to Personality Disorders (PDs). First, we will present conceptualizations and evaluations of affective mentalizing. The latter refers to one dimension of mentalization, a process by which an individual interprets his/her mental states and those of others. Lecours and Bouchard proposed a hierarchic model: the Elaboration verbale de l'affect (EVA). They also developed an empiric methodology: the Grille de l'elaboration verbale de l'affect (GEVA). The methodological approach of Lecours fulfils the requirements made by Cho-Kain, Gunderson and Luyten, involving a narrower operationalization of the mentalization concept through the evaluation of its dimensions. Conceptualizations and evaluations enabled focus on mentalization psychopathology. Fonagy and Bateman studied this latter in the subjects with PDs, particularly in Borderline Personality Disorders (BPD). We describe mentalization failure, its etiology and consequences in the BPD. Several forms of mentalization psychopathology are identified. Its etiology is largely environmental. Fonagy and Bateman developed the optimum developmental model of mentalization and referred to it to explain etiology of mentalization failure in BPD. Consequences of mentalization failure explicate its functioning. Mentalization may be considered as essential in their comprehension and their care. Research about mentalization of PDs does not integrate addiction as one comorbidity factor. However, Allen, Fonagy and Bateman describe a bidirectional interaction between mentalization failure and addiction. We propose to examine the mentalization of Borderline Addictive Personality. This concept groups addictions and borderline personalities in just one clinical entity other than their links of co morbidities. PMID- 26995153 TI - The role of GSK-3 in treatment-resistant depression and links with the pharmacological effects of lithium and ketamine: A review of the literature. AB - BACKGROUND: Since the discovery of antidepressants, new treatments have emerged with fewer side effects but no greater efficacy. Glycogen synthase kinase 3 beta (GSK-3beta), a kinase known for its activity on glycogen synthesis, has in the last few years raised growing interest in biological psychiatry. Several efficient treatments in major depression have an inhibitory effect on this kinase, which could be targeted in new mood disorder treatments. METHODS: The aim of this review is to summarize findings concerning the intracellular pharmacologic effects of GSK-3beta inhibitors on mood. After a brief description of the intracellular transduction pathways implicated in both GSK-3beta and mood disorders, we reviewed the results demonstrating GSK-3beta involvement in the effects of lithium and ketamine. RESULTS: GSK-3beta can be inhibited through several mechanisms such as serine phosphorylation or binding in a proteic scaffold and others. Its inhibition is implicated in numerous cellular pathways of interest involved in neuronal growth and architecture, cell survival, neurogenesis or synaptic plasticity. This inhibition appears to be both efficient and sufficient in improving mood in animal models. In human beings, several levels of evidence show GSK-3beta inhibition with antidepressant use. Crucially, strong inhibition has been shown with lithium via the proteic scaffold PP2A/beta arrestin/AKT, and with the rapid antidepressant effect of ketamine via p70S6K. CONCLUSION: Our review focuses on mechanisms whereby the GSK-3beta pathway has a part in the antidepressant effect of lithium and ketamine. This article highlights the importance of translational research from cell and animal models to the clinical setting in order to develop innovative therapeutic targets. PMID- 26995154 TI - Sonographic Findings in Gouty Arthritis: Diagnostic Value and Association with Disease Duration. AB - The objective of this work was to evaluate the sonographic features of gouty arthritis and correlate findings with disease duration. The study was conducted on 100 patients in ambulatory care aged >=40 y. Inclusion criteria included mono- or oligo-arthritis with effusion of the knee or the first metatarsophalangeal (MTP) joint and no known history of gout. A complete medical history was obtained with emphasis on the known risk factors or causes of gouty arthritis. A 12-MHz Medison linear probe was used for ultrasonography (US). Synovial fluid analysis with polarizing light microscopy was performed on all patients. Ninety-eight knee joints and 33 first MTP joints were examined. Gouty arthritis was found by US in four forms: (i) floating echogenic foci in effusion fluid or Baker cysts, (ii) deposits on the cartilage surface (double contour sign), (iii) erosions and (iv) mature tophus/tophi. These were found in 78.9%, 42.3%, 39.4% and 28.2% of patients, respectively. The overall sensitivity and specificity of US in detecting gout (as defined by the clinical gold standard, i.e., detection of urate crystals by polarizing light microscopy) were 85.9% and 86.7%, respectively. Detection of echogenic foci in effusion fluid was associated with the shortest duration of symptoms (median duration 2 y) followed by double contour sign (3.5 y), erosions (4 y) and tophus (12.5 y). Sonographic findings in gout can be assigned a temporal pattern, with echogenic foci being associated with the shortest and full tophus formation with the longest disease duration. PMID- 26995155 TI - Fetal Gene Therapy for Ornithine Transcarbamylase Deficiency by Intrahepatic Plasmid DNA-Micro-Bubble Injection Combined with Hepatic Ultrasound Insonation. AB - We evaluated the therapeutic efficacy of hepatic transfection of plasmid DNA using micro-bubbles and ultrasound insonation for fetal correction of ornithine transcarbamylase (OTC) deficiency in mice. Twenty-three sparse-fur heterozygous pregnant mice (day 16 of gestation) were divided into three groups: injection of plasmid-DNA micro-bubble mixture into fetal liver with ultrasound insonation (Tr, n = 11); control group 1 (C1), injection of plasmid-DNA micro-bubble mixture into fetal liver with no insonation (n = 5); and control group 2 (C2), injection of saline-micro-bubble mixture into fetal liver with ultrasound insonation (n = 7). Levels of blood ammonia and urinary orotic acid were significantly lower in the Tr group than in the C1 and C2 groups (p < 0.05, p < 0.01, respectively), whereas OTC activity was not different between groups. Therefore, ultrasound insonation with micro-bubbles enhanced plasmid DNA transfection into fetal mouse liver, leading to one of the therapeutic methods in ammonia metabolism. This might provide more time for OTC-deficient infants until liver transplantation. PMID- 26995157 TI - Effects of yarn types and fabric types on the compliance and bursting strength of vascular grafts. AB - The use of vascular grafts to replace damaged native vessels plays a significant role in clinical cardiovascular disease treatment. Comparable mechanical properties of small-diameter vascular grafts to that of native vessels are crucial and challenging. This study examines how different fabrics and yarns influence the mechanical properties of vascular grafts and evaluate the effectiveness of vascular grafts being used as native vessels. Five wrapped yarns are made into braids, warp knits, and weft knits. These knits are incorporated with PVA via freeze-thawing in order to form vascular grafts that are evaluated with circular properties and bursting strength tests. The test results indicate that the number of freeze-thawing cycles is related to the compliance and bursting strength of vascular grafts. In addition, the combination of spandex fibers improves the compliance of both the fabrics and vascular grafts. PMID- 26995158 TI - A systematic review of the impact of the use of social networking sites on body image and disordered eating outcomes. AB - A large body of literature has demonstrated mass media effects on body image and disordered eating. More recently, research in this area has turned to 'new' forms of media, such as the Internet, and particularly Social Networking Sites (SNSs). A systematic search for peer-reviewed articles on SNS use and body image and eating disorders resulted in 20 studies meeting specific inclusion criteria. As a whole, these articles demonstrated that use of SNSs is associated with body image and disordered eating. Specific SNS activities, such as viewing and uploading photos and seeking negative feedback via status updates, were identified as particularly problematic. A small number of studies also addressed underlying processes and found that appearance-based social comparison mediated the relationship between SNS use and body image and eating concerns. Gender was not found to be a moderating factor. It was concluded that, although there is a good deal of correlational research supporting the maladaptive effect of SNS use on body image and disordered eating, more longitudinal and experimental studies are needed. PMID- 26995156 TI - Acyl CoA synthetase-1 links facilitated long chain fatty acid uptake to intracellular metabolic trafficking differently in hearts of male versus female mice. AB - RATIONALE: Acyl CoA synthetase-1 (ACSL1) is localized at intracellular membranes, notably the mitochondrial membrane. ACSL1 and female sex are suggested to indirectly facilitate lipid availability to the heart and other organs. However, such mechanisms in intact, functioning myocardium remain unexplored, and roles of ACSL1 and sex in the uptake and trafficking of fats are poorly understood. OBJECTIVE: To determine the potential for ACSL1 and sex-dependent differences in metabolic trapping and trafficking effects of long-chain fatty acids (LCFA) within cardiomyocytes of intact hearts. METHODS AND RESULTS: (13)C NMR of intact, beating mouse hearts, supplied (13)C palmitate, revealed 44% faster trans sarcolemmal uptake of LCFA in male hearts overexpressing ACSL1 (MHC-ACSL1) than in non-transgenic (NTG) males (p<0.05). Acyl CoA content was elevated by ACSL1 overexpression, 404% in males and 164% in female, relative to NTG. Despite similar ACSL1 content, NTG females displayed faster LCFA uptake kinetics compared to NTG males, which was reversed by ovariectomy. NTG female LCFA uptake rates were similar to those in ACSL1 males and ACSL1 females. ACSL1 and female sex hormones both accelerated LCFA uptake without affecting triglyceride content or turnover. ACSL1 hearts contained elevated ceramide, particularly C22 ceramide in both sexes and specifically, C24 in males. ACSL1 also induced lower content of fatty acid transporter-6 (FATP6) indicating cooperative regulation with ACSL1. Surprisingly, ACSL1 overexpression did not increase mitochondrial oxidation of exogenous palmitate, which actually dropped in female ACSL1 hearts. CONCLUSIONS: ACSL1-mediated metabolic trapping of exogenous LCFA accelerates LCFA uptake rates, albeit to a lesser extent in females, which distinctly affects LCFA trafficking to acyl intermediates but not triglyceride storage or mitochondrial oxidation and is affected by female sex hormones. PMID- 26995159 TI - Clinical Outcomes and Toxicity of Proton Radiotherapy for Breast Cancer. AB - Proton beam radiotherapy (PBT) represents a rapidly expanding modality for the treatment of several malignancies. We examined the current state of PBT for breast cancer to evaluate its role in the modern era of breast radiotherapy. Systematic searches were performed using PubMed, EMBASE, and abstracts from the American Society for Radiation Oncology, American Society of Clinical Oncology, and Particle Therapy Co-Operative Group of North America annual meetings, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Nine original investigations were analyzed. Despite the dearth of overall data, skin toxicity after PBT might be equivalent or better than that of photons. Conventionally fractionated breast/chest wall PBT produces grade 1 dermatitis rates of approximately 25% and grade 2 dermatitis in 71% to 75%. This is comparable or improved over the published rates for photons. The incidence of esophagitis was decreased if the target coverage was compromised in the medial supraclavicular volume, a finding that echoes previous results with photon radiotherapy. The rates of esophagitis were also comparable to the previous data for photons. Using PBT-based accelerated partial breast irradiation, the rates of seroma/hematoma and fat necrosis were comparable to those reported in the existing data. Radiation pneumonitis and rib fractures remain rare. PBT offers excellent potential to minimize the risk of cardiac events, keeping the mean heart dose at <= 1 Gy. However, definitive clinical experiences remain sparse. The recently begun randomized trial of protons versus photons will further aid in providing robust conclusions. PMID- 26995160 TI - Corrigendum. PMID- 26995163 TI - Erratum. PMID- 26995161 TI - Hypoglycin A Concentrations in Maple Tree Species in the Netherlands and the Occurrence of Atypical Myopathy in Horses. AB - BACKGROUND: Atypical myopathy (AM) in horses is caused by the plant toxin hypoglycin A, which in Europe typically is found in the sycamore maple tree (Acer pseudoplatanus). Owners are concerned about whether their horses are in danger if they graze near maple trees. HYPOTHESIS/OBJECTIVES: To measure hypoglycin A in the most common maple tree species in the Netherlands, and to determine whether concentration of toxin is a predictor of AM in horses. METHODS: A total of 278 samples of maple tree leaves, sprouts, and seeds were classified by species. Mean concentrations of hypoglycin A were compared for the type of sample, the season and the occurrence of AM in the pasture (non-AM versus AM). Statistical analysis was performed using generalized a linear model (SPPS22). RESULTS: Almost all Acer pseudoplatanus samples contained hypoglycin A, with concentrations differing significantly among sources (P < .001). Concentrations were significantly higher in seeds from the AM group than in seeds from the non-AM group (856 +/- 677 and 456 +/- 358 mg/kg, respectively; P = .039). In sprouts and leaves this was not the case. Acer platanoides and Acer campestre samples did not contain detectable concentrations of hypoglycin A. CONCLUSIONS AND CLINICAL IMPORTANCE: Acer platanoides and campestre seem to be safe around paddocks and pastures, whereas almost all Acer pseudoplatanus samples contained hypoglycin A. In all AM cases, Acer pseudoplatanus was found. Despite significantly higher concentration of hypoglycin A in seeds of pastures where AM has occurred, individual prediction of AM cannot be made by measuring these concentrations because of the high standard deviation. PMID- 26995164 TI - Corrigendum. PMID- 26995162 TI - Increased follistatin associated with decreased gait speed among old adults. AB - BACKGROUND: Low gait speed is associated with inflammation and muscle strength. Follistatin, a glycosylated plasma protein, is involved in inflammatory diseases, bone metabolism, muscle strength and cognition. However, research regarding the relationship between follistatin and gait speed in elderly individuals is limited. In this study, we aimed to examine the association between follistatin and gait speed in older adults. METHODS: This cross-sectional, observational study included 205 ambulatory individuals aged >= 65 years. The baseline measures included 15-foot walking time, a structured questionnaire, grip strength and biomarkers, including follistatin and myostatin levels. Multiple linear regression was used to determine the change in gait speed for each 1 pg/mL increase in serum follistatin level. An extended model approach with a quartile based analysis of serum follistatin levels was conducted. RESULTS: In the linear regression model, the beta coefficient, representing the change in gait speed for each 1 pg/mL increase in serum follistatin level, was -0.308 (P < 0.001). After additional adjustment for relevant covariates, the beta coefficient changed slightly, although the negative correlation remained (all P <= 0.001). After controlling for multiple covariates, participants in the highest serum follistatin level quartile had a significantly lower gait speed than those in the lowest quartile (all P for trend < 0.001). CONCLUSIONS: A higher follistatin level was independently associated with lower gait speed in community-dwelling elderly individuals; this suggests that serum follistatin level may be an indicator of mobility in elderly persons and may more particularly represent lower extremity function. PMID- 26995165 TI - Catheterization and Cardiovascular Interventions CIT special issue: Editor in chief editorial. PMID- 26995166 TI - Facts speak louder than words. PMID- 26995167 TI - Tangled-up and blue: releasing the regulatory chokehold on take-home naloxone. PMID- 26995168 TI - Intranasal naloxone soon to become part of evolving clinical practice around opioid overdose prevention. PMID- 26995169 TI - Radical red tape reduction by government supported nasal naloxone: the Norwegian pilot project is innovative, safe and an important contribution to further development and dissemination of take-home naloxone. PMID- 26995170 TI - Ethical issues and stakeholders matter. PMID- 26995171 TI - Ensure global access to naloxone for opioid overdose management. PMID- 26995172 TI - New approved nasal naloxone welcome, but unlicensed improvised naloxone spray kits remain a concern: proper scientific study must accompany innovation. PMID- 26995173 TI - Commentary on Roberts et al. (2016): Bupropion and varenicline are efficacious and well-tolerated cessation medications for smokers with serious mental illness. PMID- 26995174 TI - Commentary on Ogeil et al. (2016): Explaining increased alcohol-related harm and stable per capita consumption in Australia. PMID- 26995175 TI - Commentary on Imtiaz et al. (2016): The burden of disease attributable to cannabis-implications for policy. PMID- 26995178 TI - African Immigrants in Low-Wage Direct Health Care: Motivations, Job Satisfaction, and Occupational Mobility. AB - This study explores motivations, job satisfaction, and overall perceived occupational mobility for African immigrants working in low-wage direct health care occupations. The study uses qualitative semi-structured interviews with a sample of thirty African immigrant workers in the greater Pittsburgh metropolitan area. Results show that four major themes captured the motivations of interviewees for doing direct care work: passion for care work, quick money, easily obtained employment, and direct care work as a pathway to other health occupations. The majority of the interviewees were satisfied with their jobs, yet almost all of them saw their occupations as temporary or transitional employment. Most of the interviewees also saw their jobs as lacking occupational mobility. In light of the increased national demand for direct care workers, the growing numbers of immigrants in the direct care labor force, and the high turnover and low retention rates of direct care workers overall, the study suggests that more must be done to make direct care work attractive and rewarding for African immigrant workers. PMID- 26995179 TI - Predictors of Obesity Among Nigerian Immigrants in the United States. AB - Obesity is a highly prevalent cardiovascular disease risk factor globally and in African-descent populations. A cross-sectional study of obesity among a Nigerian immigrant sample population in the United States was conducted. Data was obtained through a web-based survey. Spearman's correlation and logistic regression were used to determine sociodemographic and behavioral determinants of obesity. The results showed no significant relationship between obesity and education, socioeconomic status, length of stay, and level of physical activity. However, we identified a significant association between weekly consumption of alcohol and all obesity (OR 1.78, 95 % CI 1.091, 2.919), and moderate/morbid obesity (OR 2.46, 95 % CI 1.213, 4.999), and between gender and moderate/morbid obesity-men were less likely (OR .030, 95 % CI .001, .733) to be obese. These findings provide strong evidence to inform targeted screening for excessive alcohol consumption along with other primary prevention strategies that may reduce the prevalence of obesity among the Nigerian immigrant population. PMID- 26995181 TI - Syrian Refugees, Health and Migration Legislation in Turkey. AB - This paper discusses the crucial effects of Turkish health and migration laws on Syrian refugees' access to public health services and social determinants of health. Key aspects of current Turkish laws affect the health of both refugees and Turkish citizens in many ways. The huge influx of refugees is increasing communicable disease risks, overcrowding hospitals, and more generally straining financial and health resources. Turkey's United Nations membership and its candidacy for European Union (EU) have led to increased alignment of Turkey's refugee and migration policies with international law. Major differences remain, however, and Turkey's remaining noncompliance with international refugee laws is a major force driving Syrian refugee's flight to EU countries, as refugees desperately seek the right to better health and social services. PMID- 26995180 TI - Segmentation of Mexican-Heritage Immigrants: Acculturation Typology and Language Preference in Health Information Seeking. AB - With the fast growing number of Mexican immigrants in the United States, more attention is needed to understand the relationship between acculturation and language preference in health information seeking. Latent class analysis provides one useful approach to understanding the diversity in sample of Mexican immigrants (N = 238). Based on 13 linguistic, psychological and behavioral indicators for acculturation, four discrete subgroups were characterized: (1) Less acculturated, (2) Moderately acculturated, (3) Highly acculturated, (4) Selectively bicultural. A Chi-square test revealed that three sub-groups were significantly different in language preference when seeking health information. Less acculturated and moderately acculturated groups sought health information in Spanish, whereas the highly acculturated group preferred English for health information. Selectively bicultural group preferred bilingual health information. Implications for health campaign strategies using audience segmentation are discussed. PMID- 26995182 TI - Regional Specialisation of T Cell Subsets and Apoptosis in the Human Gut Mucosa: Differences Between Ileum and Colon in Healthy Intestine and Inflammatory Bowel Diseases. AB - BACKGROUND AND AIMS: There is very limited information regarding region-specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. METHODS: T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4(+)CD25(+)FOXP3(+)], double positive [DP, CD3(+)CD4(+)CD8(+)] and double negative T cells [DN, CD3(+)CD4(-)CD8(-)], immunohistochemistry [FOXP3, caspase-3], and real-time polymerase chain reaction [PCR] [IFN-gamma, IL-17-A, and FOXP3] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases. RESULTS: Healthy colon showed higher percentages of Treg, Th17, and DN, and lower numbers of DP T cells compared with ileum [p < 0.05]. Some but not all region-specific differences were lost in inflammatory conditions. Disease-specific patterns were found: a Th1/Th17 pattern and a Th17 pattern in Crohn's disease and ulcerative colitis respectively, whereas a reduction in Th1/Th17 was found in microscopic colitis. In colonic Crohn's disease and microscopic colitis, DN T cells had a pattern inverse to that of Th1/Th17 (increase in microscopic colitis [p < 0.05] and decrease in Crohn's disease [p < 0.005]). Higher levels of lymphocyte apoptosis were found in healthy colon compared with the ileal counterparts [p = 0.001]. All forms of colonic inflammation presented a dramatic decrease in apoptosis compared with healthy colon. By contrast ileal Crohn's disease showed higher levels of cleaved-Caspase(+) CD3(+) cells. CONCLUSIONS: Immunological differences exist in healthy gastrointestinal tract. Inflammatory processes overwhelm some location-specific differences, whereas others are maintained. Care has to be taken when analysing immune response in intestinal inflammation, as location-specific differences may be relevant. PMID- 26995183 TI - Fibrotic and Vascular Remodelling of Colonic Wall in Patients with Active Ulcerative Colitis. AB - BACKGROUND AND AIMS: Intestinal fibrosis is a complication of inflammatory bowel disease [IBD]. Although fibrostenosis is a rare event in ulcerative colitis [UC], there is evidence that a fibrotic rearrangement of the colon occurs in the later stages. This is a retrospective study aimed at examining the histopathological features of the colonic wall in both short-lasting [SL] and long-lasting [LL] UC. METHODS: Surgical samples of left colon from non-stenotic SL [<= 3 years, n = 9] and LL [>= 10 years, n = 10] UC patients with active disease were compared with control colonic tissues from cancer patients without UC [n = 12] to assess: collagen and elastic fibres by histochemistry; vascular networks [CD31/CD105/nestin] by immunofluorescence; parameters of fibrosis [types I and III collagen, fibronectin, RhoA, alpha-smooth muscle actin [alpha-SMA], desmin, vimentin], and proliferation [proliferating nuclear antigen [PCNA]] by western blot and/or immunolabelling. RESULTS: Colonic tissue from both SL-UC and LL-UC showed tunica muscularis thickening and transmural activated neovessels [displaying both proliferating CD105-positive endothelial cells and activated nestin-positive pericytes], as compared with controls. In LL-UC, the increased collagen deposition was associated with an up-regulation of tissue fibrotic markers [collagen I and III, fibronectin, vimentin, RhoA], an enhancement of proliferation [PCNA] and, along with a loss of elastic fibres, a rearrangement of the tunica muscularis towards a fibrotic phenotype. CONCLUSIONS: A significant transmural fibrotic thickening occurs in colonic tissue from LL-UC, together with a cellular fibrotic switch in the tunica muscularis. A full-thickness angiogenesis is also evident in both SL- and LL-UC with active disease, as compared with controls. PMID- 26995184 TI - Efficacy and Safety of Adalimumab for Paediatric Crohn's Disease: A Systematic Review. AB - BACKGROUND AND AIM: Adalimumab is well-established therapy for adults with Crohn's disease [CD]. The aim of the study was to systematically assess the published evidence on the efficacy and safety of adalimumab for Crohn's disease in children. METHODS: MEDLINE, EMBASE, the Cochrane Library, and abstracts from the main gastroenterological meetings in the past 5 years were systematically searched up to July 2015 for randomised controlled trials and observational studies on the efficacy and safety of adalimumab for Crohn's treatment in children and adolescents. RESULTS: A total of 14 studies [1 randomised controlled trial, 13 case series], altogether including 664 patients [age: 1.9 to 21 years] were available for analysis. The studies differed with respect to patients' characteristics, including percentage of infliximab-naive patients, disease duration, site of the disease, adalimumab doses, treatment duration, and follow up period. The pooled remission rates were: 30% [n = 93/309] at 4 weeks, 54% [n = 79/145] at 3 months, 45% [n = 18/40] at 4 months, 42% [n = 146/345] at 6 months, 57% [n = 20/35] at 8 months, and 44% [n = 169/383] at 12 months. Of the total patients, 6% [n = 13/207] were classified as primary non-responders and 12% [n = 69/599] had severe adverse events reported including 2 deaths and 1 medulloblastoma. Withdrawal rate due to adverse events reported in one study was 35% [n = 64/182]. CONCLUSION: According to low-quality evidence based mainly on case series, approximately half of children with Crohn's disease on adalimumab therapy achieve remission during the first year of the therapy with reasonable safety profile. There is still a need for high-quality evidence on effectiveness and safety of adalimumab for paediatric Crohn's disease. PMID- 26995185 TI - Relationship of Body Mass Index to Clinical Outcomes after Infliximab Therapy in Patients with Crohn's Disease. AB - BACKGROUND & AIMS: There are conflicting data for the role of obesity in Crohn's disease (CD) and the effect on long-term clinical outcomes is poorly studied. Some evidence suggests obesity is associated with diminished responsiveness to biological agents, especially anti-tumour necrosis factor antibodies. METHODS: We aimed to examine the influence of body mass index (BMI) on the response to infliximab in CD in a retrospective analysis. The outcomes of interest within 12 months were: (1) Composite loss of response (CD-related flare or surgery; LOR); (2) any CD-related surgery (CDRS); and (3) CD-related intestinal resectional surgery (CDRIS). RESULTS: A total of 388 patients were included. The mean BMI was 24.2kg/m(2) [+/- standard deviation (SD) 5.1]. Of the 388 patients, 137 (35.4%) were overweight (BMI: 25-29.9kg/m(2)) or obese (BMI: >=30kg/m(2))-160 (41.6%) patients had LOR during the 12 months follow-up; 121 (31.4%) required CDRS, and 109 (28.2%) required CDRIS. Multivariate analysis showed that increasing BMI (per unit, kg/m(2) increase) reduced the risk of LOR [odds ratio (OR): 0.98], CDRS (OR: 0.95), and CDRIS (OR: 0.95). Rates for all outcomes were higher, but not significantly so, in the extreme categories (underweight and obese) and lower in the underweight categories compared with normal BMI. Exclusion of the obese category of patients strengthened this relationship. CONCLUSIONS: Body mass index at first infusion of infliximab has a non-linear relationship with outcomes at 12 months. The worst outcomes are at the extremes of weight (underweight and obese categories). Increasing BMI is associated with a modest reduction in risk of LOR, CDRS, and CDRIS within 12 months, increasing with the exclusion of the obese category. PMID- 26995186 TI - Costly rejection of wrongdoers by infants and children. AB - How unappealing are individuals who behave badly towards others? We show here that children and even infants, although motivated by material rewards, are nonetheless willing to incur costs to avoid "doing business" with a wrongdoer. When given the choice to accept a smaller offering from a do-gooder or a larger offering from a wrongdoer, children and infants chose to accept the smaller offering. It was only when the difference between the offerings was very large that their aversion to the wrongdoer was overcome by personal incentives. These findings show that a willingness to forgo self-interests when faced with wrongdoers is a fundamental aspect of human nature. PMID- 26995187 TI - Vagueness, graded membership, and conceptual spaces. AB - This paper is concerned with a version of Kamp and Partee's account of graded membership that relies on the conceptual spaces framework. Three studies are reported, one to construct a particular shape space, one to detect which shapes representable in that space are typical for certain sorts of objects, and one to elicit degrees of category membership for the various shapes from which the shape space was constructed. Taking Kamp and Partee's proposal as given, the first two studies allowed us to predict the degrees to which people would judge shapes representable in the space to be members of certain categories. These predictions were compared with the degrees that were measured in the third study. The comparison yielded a test of the account of graded membership at issue. The outcome of this test was found to support the conceptual spaces version of Kamp and Partee's account of graded membership. PMID- 26995188 TI - Hepatitis C Virus Genotype and Subtype Distribution in Patient Specimens Tested at the University of Texas Medical Branch, Galveston, Between January 2011 and November 2014. AB - Hepatitis C virus (HCV) genotype/subtype data are routinely generated in clinical laboratories to guide treatment. Genotype data can also inform genotype distribution and molecular epidemiology of HCV infections in patient populations and geographical regions that clinics/laboratories serve. The aim of this study was to determine the distribution of HCV genotypes/subtypes and their association with demographic characteristics among the patients that were routinely tested in the Molecular Diagnostics Laboratory at The University of Texas Medical Branch (UTMB) at Galveston. Among the 6573 patients tested between January 2011 and November 2014, the most frequent HCV genotype/subtype was 1a (65.3%), followed by 3a (11.5%), 1b (10.4%), and 2b (8.8%). Combined, genotype 4 and genotype 6 were found in less than 1% of this cohort. Approximately 1.3% of the patients presented multiple genotypes/subtypes. Factors independently associated with genotypes and subtypes were race/ethnicity, sex, and patient age. PMID- 26995189 TI - 21st International Chromosome Conference-Foz do Iguacu, Brazil. PMID- 26995190 TI - Diagnostic values of serum cathepsin B and D in patients with nasopharyngeal carcinoma. AB - BACKGROUND: The diagnostic and prognostic significance of increased cathepsin B (CTSB) and cathepsin D (CTSD) concentration in the serum of cancer patients were evaluated for some tumor types. High expression of CTSD and CTSB was detected in biopsy tissues from nasopharyngeal carcinoma (NPC). However, whether CTSD and CTSB serve as diagnostic and prognostic markers of NPC remains unclear. METHODS: Serum samples were collected from 40 healthy volunteers and 80 NPC patients enrolled in the study. CTSB and CTSD in the serum samples were detected using enzyme-linked immunosorbent assay (ELISA). Concomitantly, the relationship between CTSB and CTSD concentrations and clinicopathological prognosis was assessed. The sensitivity and specificity of the two components in the diagnosis of NPC were evaluated in 80 NPC patients. RESULTS: ELISA analysis showed that in the sera obtained from NPC patients, the CTSB concentration was 12.5 +/- 3.5 mg/L (median, 12.4 mg/L), and the CTSD concentration was 15.7 +/- 8.7 mg/L (median, 14.7 mg/L). CTSB and CTSD levels were significantly higher in the NPC patient population compared to the healthy control population (p = 0.001; p = 0.001, respectively). The presence of CTSB and CTSD in the serum of the patients with NPC correlated with the tumor node metastasis (TNM) scores (p = 0.001). Other parameters were not identified to be of significance. Receiver operating characteristic (ROC) analysis showed that a cut off CTSB concentration of 12.4 mg/L had 61.9% sensitivity and 63.2% specificity in the prediction of progression free survival (Area under the curve (AUC) = 0.525; 95% CI, 39.7-65.2; p = 0.704); whereas a cut off CTSD concentration of 14.7 mg/L had 66.7% sensitivity, and 58.5% specificity (AUC = 0.552; 95% CI, 42.3-68.1; p = 0.42). CONCLUSIONS: Serum CTSB and CTSD concentrations were found to have a diagnostic value in NPC. However, the CTSB and CTSD serum levels had no prognostic role for the outcome in NPC patients. PMID- 26995193 TI - Editorial. PMID- 26995191 TI - The slow phase of chlorophyll a fluorescence induction in silico: Origin of the S M fluorescence rise. AB - In higher plants, algae, and cyanobacteria, chlorophyll (Chl) a fluorescence induction (ChlFI) has a fast (under a second) increasing OJIP phase and a slow (few minutes) PS(M)T phase, where O is for origin, the minimum fluorescence, J and I for intermediate levels, P for peak, S for a semi-steady state, M for a maximum (which is sometimes missing), and T for the terminal steady-state level. We have used a photosynthesis model of Ebenhoh et al. (Philos Trans R Soc B, 2014, doi: 10.1098/rstb.2013.0223 ) in an attempt to simulate the slow PS(M)T phase and to determine the origin of the S-M rise in Chlamydomonas (C.) reinhardtii cells. Our experiments in silico show that a slow fluorescence S-M rise (as that observed, e.g., by Kodru et al. (Photosynth Res 125:219-231, 2015) can be simulated only if the photosynthetic samples are initially in a so-called "state 2," when the absorption cross section (CS) of Photosystem II (PSII) is lower than that of PSI, and Chl a fluorescence is low (see, e.g., a review by Papageorgiou and Govindjee (J Photochem Photobiol B 104:258-270, 2011). In this case, simulations show that illumination induces a state 2 (s2) to state 1 (s1) transition (qT21), and a slow S-M rise in the simulated ChlFI curve, since the fluorescence yield is known to be higher in s1, when CS of PSII is larger than that of PSI. Additionally, we have analyzed how light intensity and several photosynthetic processes influence the degree of this qT21, and thus the relative amplitude of the simulated S-M phase. A refinement of the photosynthesis model is, however, necessary in order to obtain a better fit of the simulation data with the measured ChlFI curves. PMID- 26995192 TI - Improved osteogenic vector for non-viral gene therapy. AB - Therapeutic compensation of deficient bone regeneration is a challenging task and a topic of on-going search for novel treatment strategies. One promising approach for improvement involves non-viral gene delivery using the bone morphogenetic protein-2 (BMP-2) gene to provide transient, local and sustained expression of the growth factor. However, since efficiency of non-viral gene delivery is low, this study focused on the improvement of a BMP-2 gene expression system, aiming for compensation of poor transfection efficiency. First, the native BMP-2 gene sequence was modified by codon optimisation and altered by inserting a highly truncated artificial intron (96 bp). Transfection of multiple cell lines and rat adipose-derived mesenchymal stem cells with plasmids harbouring the improved BMP 2 sequence led to a several fold increased expression rate and subsequent osteogenic differentiation. Additionally, comparing expression kinetics of elongation factor 1 alpha (EF1alpha) promoter with a state of the art CMV promoter revealed significantly higher BMP-2 expression when under the influence of the EF1alpha promoter. Results obtained by quantification of bone markers as well as osteogenic assays showed reduced sensitivity to promoter silencing effects of the EF1alpha promoter in rat adipose-derived mesenchymal stem cells. Finally, screening of several protein secretion signals using either luciferase or BMP-2 as reporter protein revealed no superior candidates for potential replacement of the native BMP-2 secretion signal. Taken together, by enhancing the exogenous BMP-2 expression system, low transfection efficiencies in therapeutic applications can be compensated, making safe non-viral systems even more suitable for tissue regeneration approaches. PMID- 26995194 TI - Electrokinetic ion transport in confined micro-nanochannel. AB - In this paper, a confined micronanochannel is presented to concentrate ions in a restricted zone. A general model exploiting the Poisson-Nernst-Plank equations coupled with the Navier-Stokes equation is employed to simulate the electrokinetic ion transport. The influences of the micronanochannel dimension and the surface charge density on the potential distribution, the ion concentration, and the fluid flow are investigated. The numerical results show that the potential drop depends mainly on the nanochannel, instead of the confined channel. Both decreasing the width and increasing the length enhance the ion enrichment performance. For a given nanochannel, ultimate value of ion concentration may be determined by the potential at the center point of the nanochannel. The study also shows that the enrichment stability can be improved by increasing the micronanochannel width, decreasing the micronanochannel length and reducing the surface charge density. PMID- 26995195 TI - Diffusioosmotic flow in rectangular microchannels. AB - The diffusioosmosis of an electrolyte solution inside a uniformly charged rectangular channel at steady locally developed conditions is the subject of this study. Utilizing a finite element based numerical procedure, we try to estimate the errors incurred by modeling the actual rectangular geometry of typical microchannels as a slit. We demonstrate that the flow pattern and direction are generally dependent upon the width-to-height ratio of the channel. Such a finding, besides showing the ineffectiveness of the slit geometry in representing a rectangular channel of small aspect ratio, informs us of another mechanism of controlling the diffusioosmotic flow. Inspections of the mean velocity reveal that, although it drastically grows by increasing the aspect ratio at smaller values of this parameter, no significant change is observed when the aspect ratio is 5 or higher. The same trend is observed when EDL is shrunk and is considered as a basis for the introduction of a slip-like velocity, similar to the concept of the Helmholtz-Smoluchowski electroosmotic velocity, which will be of high practical importance when dealing with a micronsized channel. Because of its significance, an expression is presented for this slip velocity utilizing the curve fitting of the results, assuming a typical Peclet number. PMID- 26995196 TI - Standardized genotyping of HLA STR by CE as surrogate for HLA class I and II markers and for identification of HLA identical siblings. AB - Linkage disequilibria (LD) between alleles and haplotypes of human leucocyte antigen, locus A (HLA) and STR loci located in the human major histocompatibility complex were analyzed in order to investigate whether or not HLA alleles and haplotypes are predictable by alleles or haplotypes of HLA STRs. Standardized genotyping of eight STR loci (D6S2972, D6S2906, D6S2691, D6S2678, D6S2792, D6S2789, D6S273, and DQIV) was performed by CE on 600 individuals from 150 Austrian Caucasoid families with known HLA-A,-B,-C and -DRB1 typing. From those, 576 full haplotypes of four HLA and eight STR loci were obtained. Haplotypes of two flanking STRs predicted HLA alleles and two-locus HLA haplotypes better than single STR alleles, except HLA-DRB1 alleles (92% were in LD with DQIV alleles only). A percentage of 65-86% of three and four-locus HLA haplotypes were in LD with haplotypes of three, four, and eight of their flanking STR loci including numerous clear-cut predictions (20-61%). All eight and a set of the four most informative STR loci D6S2972, D6S2678, D6S2792, and DQIV could identify all HLA identical and nonidentical siblings in 138 pairs of siblings. The results of this proof of concept study in Austrian Caucasoids show, that HLA STRs can aid the definition of HLA-A,-B,-C,-DRB1 haplotypes and the selection of sibling donors for stem cell transplantation. PMID- 26995198 TI - Understanding One's Own Emotions in Cognitively-Able Preadolescents with Autism Spectrum Disorder. AB - There are still no straightforward answers as to whether understanding one's own emotions is impaired in autism spectrum disorder (ASD). This study evaluated the perception of one's own different emotions, based on the relevant section of the Autism Diagnostic Observation Schedule Module 3 test. Forty boys, aged 8-11 years, 20 diagnosed with ASD (IQ >= 85) and 20 typically developing children were included. Description of events that elicited specific emotions in ASD was characterized by more 'odd' statements and 'no responses' and less use of content related to 'social situations', 'interpersonal' and 'self-awareness'. More 'no responses' and odd statements were associated with the severity of ASD symptoms. Clinicians should be aware of these differentiating factors during the diagnostic process of ASD. PMID- 26995199 TI - High Prevalence of Hypovitaminosis D in Postmenopausal Women with Type 2 Diabetes Mellitus. AB - The link between vitamin D and type 2 diabetes mellitus (T2DM) is intensively studied. This study aims to define the serum concentration of 25-hydroxyvitamin D (25-OH D) and to investigate the relationship between 25-OH D status, glycated hemoglobin (HbA1c) and body composition in postmenopausal women with T2DM and in non-diabetic controls. In this cross-sectional study, 75 women with T2DM and 32 control subjects were selected. Serum 25-OH D, intact parathyroid hormone (PTH), calcium, fasting glucose and HbA1c, were measured. The mean 25-OH D level was 21.4+/-11.4 ng/ml (range 4.1-50.7 ng/ml) in diabetic women and 30.3+/-9.4 ng/ml (range 10.8-54.2 ng/ml) in control group (p<0.001). The prevalence of hypovitaminosis D (<30 ng/ml) was higher in vitamin D3 non-supplemented T2DM women (89% vs. 63% controls); the difference diminished in vitamin D3 (500-1000 IU per day) supplemented subgroups (45% diabetics vs. 42% controls). In T2DM women, 25-OH D levels were not associated to HbA1c, duration of diabetes, fasting glucose and PTH levels, however, 25-OH D levels negatively associated with body mass index (p=0.011), total body fat mass (p=0.005) and total body lean mass (p=0.004). The prevalence of hypovitaminosis D is higher in non-supplemented postmenopausal women with T2DM than in non-diabetic controls (89% vs. 63%). Obesity is a risk factor for vitamin D insufficiency in T2DM postmenopausal women. Further studies evaluating relationships between fat, muscle, bone and vitamin D metabolism in T2DM patients are warranted. PMID- 26995200 TI - A Comparison of Salivary Steroid Levels during Diagnostic Tests for Adrenal Insufficiency. AB - Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD+/-4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD+/-3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 MUg, 10 MUg, and 250 MUg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 MUg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost effective alternative. This dose also largely eliminates both false negative and false positive results. PMID- 26995201 TI - Combination of Steroids and Azathioprine in the Treatment of Ormond's Disease--A Single Centre Retrospective Analysis. AB - We present a retrospective analysis of patients treated in our Department of Clinical Biochemistry, Haematology and Immunology, Na Homolce Hospital, during 1997-2013 for Ormond's disease. We analyse the clinical history, diagnostic approaches, surgical, and immunosuppressive therapies and their subsequent effect on our patients. 28 patients treated for Ormond's disease were included. Patients with established disease activity (26 patients) were given immunosuppressive treatment, using corticosteroids in combination with azathioprine. Treatment response was evaluated using clinical symptomatology, inflammatory parameters and imaging methods. In the cohort as a whole, immunosuppressive therapy was applied in 26 patients; in two patients it was not used as no inflammatory activity was found with the disease. In all 26 patients, computed tomography showed that immunosuppressive treatment resulted in partial or complete regression of inflammatory infiltrate. Out of the total number of 26 patients, two patients experienced disease exacerbation 7 and 16 months after the immunosuppressive treatment was discontinued. The longest follow-up period was 16 years; the shortest one was 21 months. Idiopathic retroperitoneal fibrosis--Ormond's disease -is a disease with serious complications. Standard treatment involves a combination of surgery and immunosuppressive treatment. The combination of corticosteroids and azathioprine represents a potentially safe and useful method of treatment. PMID- 26995202 TI - L1 Retrotransposons Are Transcriptionally Active in Hippocampus of Rat Brain. AB - LINE1 (L1) is an autonomous, non-LTR retrotransposon and the L1 family of retrotransposons constitute around 17%, 20% and 23% in the human, mouse and rat genomes respectively. Under normal physiological conditions, the retroelements remain by and large transcriptionally silent but are activated in response to biotic and abiotic stress conditions and during perturbation in cellular metabolism. They have also been shown to be transiently activated under certain developmental programs. Using RT-PCR, we show that the L1 elements are transcriptionally active in the hippocampus region of the brain of four-month-old rat under normal conditions without any apparent stress. Twenty non-redundant LINE1-specific reverse transcriptase (RTase) sequences form ORF2 region were isolated, cloned and sequenced. Full length L1 element sequences complementary to the isolated sequences were retrieved from the L1 database. In silico analysis was used to determine the presence of these retroelements proximal (up to 10 kb) to the genes transcriptionally active in the hippocampus. Many important genes were found to be in close proximity of the transcriptionally active L1 elements. Transcriptional activation of the elements possibly affects the expression of the neighbouring genes. PMID- 26995203 TI - Juxtarenal Mycotic Aneurysm as a Complication of Acute Exacerbation of Chronic Cholecystitis Treated by Resection and Replacement by a Fresh Allograft. AB - We present a case of a female patient with infectious (mycotic) juxtarenal abdominal aneurysm with atypical symptoms beginning as acute exacerbation of chronic cholecystitis. Apart from common antibiotic treatment, the patient successfully underwent resection of the diseased segment and replacement by a fresh allograft in order to reduce the risk of infection of the graft, but with the need of subsequent life-long immunosuppressive therapy. Perioperative monitoring of the spinal cord by near infrared spectroscopy was used to identify possible spinal ischemia. The choice of the fresh allograft was based on our experience supported by review of the literature. PMID- 26995204 TI - Snakebite Envenoming by Sochurek's Saw-scaled Viper Echis Carinatus Sochureki. AB - A snake breeder, 47-years-old man, was bitten by the saw-scaled viper (Echis carinatus sochureki). After admission to Toxinology Centre, within 1.5 h, laboratory evaluation showed clotting times prolonged to non-measurable values, afibrinogenaemia, significantly elevated D-dimers, haemolysis and myoglobin elevation. Currently unavailable antivenom was urgently imported and administered within 10 hours. In 24 hours, oligoanuric acute kidney injury (AKI) and mild acute respiratory distress syndrome (ARDS) developed. Despite administration of 10 vials of urgently imported Polyvalent Snake Antivenom Saudi Arabia, the venom induced consumption coagulopathy (VICC) and AKI persisted. Another ten vials of antivenom were imported from abroad. VICC slowly subsided during the antivenom treatment and disappeared after administration of total 20 vials during 5 day period. No signs of haemorrhage were present during treatment. After resolving VICC, patient was transferred to Department of Nephrology for persisting AKI and requirement for haemodialysis. AKI completely resolved after 20 days. Despite rather timed administration of appropriate antivenom, VICC and AKI developed and the quantity of 20 vials was needed to cease acute symptoms of systemic envenoming. The course illustrates low immunogenicity of the venom haemocoagulation components and thus higher requirements of the antivenom in similar cases. PMID- 26995205 TI - Terlipressin Induced Severe Hyponatremia. AB - Terlipressin is a vasopressin analogue used for its vasoconstrictor effect in the treatment of variceal bleeding. Despite its good safety profile compared to vasopressin, some adverse reactions may occur during its use - e.g. hyponatremia. We describe a case of a cirrhotic patient with active variceal bleeding treated during two separate hospitalizations with terlipressin. In both drug treatment periods, severe laboratory hyponatremia developed. After terlipressin discontinuation, mineral disbalance corrected rapidly. Positive dechallenge and rechallenge corresponding to the drug administration schedule confirms the causality between terlipressin administration and hyponatremia. Hyponatremia was preceded with substantial fluid retention in both episodes. In this case report we want to highlight the need for fluid balance monitoring immediately after first terlipressin dose, which may individually predict the patient risk for the development of hyponatremia as other risk factors have rather limited predictive value in real clinical settings. PMID- 26995206 TI - Contrast volume reduction using third generation dual source computed tomography for the evaluation of patients prior to transcatheter aortic valve implantation. AB - OBJECTIVES: Chronic renal failure is common in patients referred for transcatheter aortic valve implantation (TAVI). CT angiography is recommended and provides crucial information prior to TAVI. We evaluated the feasibility of a reduced contrast volume protocol for pre-procedural CT imaging. METHODS: Forty consecutive patients were examined with prospectively ECG-triggered high-pitch spiral acquisition using a novel third-generation dual-source CT system; 38 ml contrast agent was used. Image quality was graded on a visual scale (1-4). Contrast attenuation was measured at the level of the aortic root and at the iliac bifurcation. RESULTS: Mean patient age was 82 +/- 6 years (23 males; 58 %). Mean attenuation/average image quality was 285 +/- 60 HU/1.5 at the aortic annulus compared to 289 +/- 74 HU/1.8 at the iliac bifurcation (p = 0.77/p = 0.29). Mean estimated effective radiation dose was 2.9 +/- 0.3 mSv. A repeat acquisition was necessary in one patient due to image quality. Out of the 35 patients who underwent TAVI, 31 (89 %) patients had no or mild aortic regurgitation. Thirty-two (91 %) patients were discharged successfully. CONCLUSION: Pre-procedural CTA with a total of 38 ml contrast volume is feasible and clinically useful, using third-generation dual-source CT, allowing comprehensive imaging for procedural success. KEY POINTS: * Reduction of contrast agent volume is crucial in patients with chronic renal failure. * Novel third generation computed tomography helps to reduce contrast agent volume. * Pre procedural CT allows comprehensive imaging for procedural success before heart valve implantation. * A low-contrast CT protocol is feasible for pre-procedural TAVI planning. PMID- 26995207 TI - Sectional Localization of a Small Hepatocellular Carcinoma in the Right Hepatic Lobe by Computed Tomography: Comparison between the Conventional and Portal Vein Tracing Methods. AB - PURPOSE: To compare the accuracy of the conventional and portal vein tracing methods in the right hepatic lobe in multidetector computed tomography (MDCT). MATERIALS AND METHODS: This retrospective study included patients with hepatocellular carcinoma (HCC) lesions in the right hepatic lobe who underwent multiphasic MDCT and C-arm CT hepatic arteriography (C-arm CTHA) for chemoembolization. The accuracies of the conventional and portal vein tracing methods were evaluated using C-arm CTHA as the gold standard. RESULTS: A total of 147 patients with 205 HCC nodules were included. The C-arm CTHA could identify all the tumour-feeding arteries and consequently demonstrated that 120 lesions were located in the anterior section, 78 in the posterior section, and 7 in the border zone. The accuracy rates of conventional vs. portal vein tracing methods were 71.7 % vs. 98.3 % for the anterior section lesions, 67.9 % vs. 96.2 % for the posterior section, and 28.6 % vs. 57.1 % for the border zone. The portal vein tracing method was more accurate than the conventional method (P<0.001). CONCLUSIONS: The portal vein tracing method should be used for sectional localization of HCCs in the right lobe, because it predicts the location more accurately than the conventional method. KEY POINTS: * Portal tracing method is more accurate than conventional method for tumour localization. * The conventional method is especially inaccurate in right anteroinferior or posterosuperior quadrants. * Scissurae between right anterior and posterior section may not be vertical but tilted. PMID- 26995208 TI - MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations. AB - OBJECTIVE: To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. METHODS: Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. RESULTS: Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 * 10-3 mm2/s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. CONCLUSION: Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. KEY POINTS: * Cervical NECs show a tendency of lesion homogeneity and lymphadenopathy * Low ADC values are found in cervical NECs * MRI is an accurate imaging modality for the cervical NEC staging. PMID- 26995209 TI - Venom from the spider Araneus ventricosus is lethal to insects but inactive in vertebrates. AB - Araneus ventricosus spider venom, which was collected by electrical stimulation, is abundant in peptides and proteins with molecular weights ranging from 2 kDa to 70 kDa as determined by gel electrophoresis and mass spectrometry. Electrophysiological experiments showed that 50 MUg/mL venom could block the voltage-gated sodium channels (VGSCs) currents of the dorsal unpaired median (DUM) neurons of Periplaneta americana cockroaches. However, 500 MUg/mL venom could not block the VGSCs currents in rat dorsal root ganglion cells or the neuromuscular transmission in isolated mouse phrenic nerve-hemidiaphragm. Moreover, we also observed that injection of the venom in P. americana gave rise to obvious envenomation symptoms, with a LD50 value of 30.7 MUg/g. Enzymatic analysis indicated that the venom possessed activities of several kinds of hydrolases including hyaluronidase and proteases. These results demonstrate that A. ventricosus venom contains bioactive components targeting insects, which are the natural prey of these spiders. Furthermore, the venom was found to be not active in vertebrate. Thus, we suggest that A. ventricosus venom contains novel insect-selective compounds that might be helpful in developing new and safe insecticides. PMID- 26995210 TI - Prospective, consecutive case series of 158 snakebite patients treated at Savannakhet provincial hospital, Lao People's Democratic Republic with high incidence of anaphylactic shock to horse derived F(ab')2 antivenom. AB - Snakebites are a seriously neglected public health problem in Lao PDR. Community based cross-sectional surveys in two districts of Savannakhet province in Southern Laos revealed an incidence of up to 1105 snakebites per 100,000 persons per year. In contrast the number of snakebite patients treated in district and provincial hospitals are low. In order to improve health care for snakebite victims, antivenom was introduced to Savannakhet provincial hospital in July 2013 and medical staff has been trained in management of venomous snakebites at the same time. After the intervention the number of snakebite patients treated at the provincial hospital increased significantly from 4 patients in 2012 to 158 snakebite patients between July 2013 and November 2015. They were included into a prospective, consecutive case series. Median age was 32 years (range 1.5-70 years) and male-to-female ratio 2.2:1. Forty patients were bitten by Malayan pit vipers, 26 by green pit vipers, 24 by cobras, including 3 cases of venom ophthalmia, 5 by kraits, 8 by non-venomous species and in 55 cases the snake could not be identified. Forty-three out of 158 patients received horse derived F(ab')2 antivenom from Queen Saovabha Memorial Institute (QSMI) in Bangkok. Twenty-three patients (53%) developed early adverse reactions (EARs) within one hour after antivenom administration, including 13 patients (30%) with severe anaphylaxis. This extremely high rate of severe EARs turns the use of antivenom into a risky intervention. In contrast a retrospective chart review from Chulalongkorn University in Bangkok found only 3.5% early reactions including 1.2% severe anaphylactic reactions using the same antivenom from QSMI between 1997 and 2006. The reason for this enormous difference remains unclear. A better understanding of the aetiology and pathophysiology behind antivenom induced anaphylaxis is crucial in order to identify patients at risk and to improve safety of antivenom administration. PMID- 26995213 TI - Corrigendum: Ultrafast Structural Fluctuations of Myoglobin-Bound Thiocyanate and Selenocyanate Ions Measured with Two-Dimensional Infrared Photon Echo Spectroscopy. PMID- 26995211 TI - The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells. AB - OBJECTIVES: Microcystin-leucine arginine (MC-LR) is produced by cyanobacteria and can accumulate in lungs through blood circulation. However, the effect of MC-LR on lung remains unclear. In this study, we investigated the chronic, low-dose effect of MC-LR on mouse lung tissues and the influence of MC-LR on mouse alveolar type II epithelial cells (ATII cells). METHODS: MC-LR was orally administered to mice at 0, 1, 10, and 40 MUg/L for 6 consecutive months and mouse lungs were obtained for histopathological and immunoblot analysis. ATII cells were cultured in various concentrations of MC-LR (0, 0.5, 5, 50, 500 nmol/L) for indicated time and the cell viability and proteins change were tested. RESULTS: Our study revealed that the chronic, low-dose MC-LR exposure induced alveolar collapse and lung cell apoptosis as well as the breach of cell junction integrity. Furthermore, following treatment with MC-LR, ATII cells could uptake MC-LR, resulting in apoptosis and disruption of cell junction integrity. CONCLUSIONS: These data support the toxic potential of low-dose MC-LR in rendering chronic injury to lung tissues. PMID- 26995214 TI - High definition endoscopy with or without I-Scan increases the detection of celiac disease during routine endoscopy. AB - BACKGROUND AND AIMS: Celiac disease remains underdiagnosed at endoscopy. We aimed to assess the utility of I-Scan (virtual chromo-endoscopy) to improve sensitivity of endoscopy to detect markers of villous atrophy in this condition. METHODS: Patients from 2 UK hospitals were studied in 3 groups. Group 1: standard high definition, white light endoscopy (WLE); Group 2: WLE plus I-Scan; Group 3: non high definition control group. The presence of endoscopic markers was recorded. At least 4 duodenal biopsies were taken from all patients. Serology was performed concurrently and observations were compared with histology. RESULTS: 758 patients (62% female, mean age 52) were recruited (Group 1: 230; Group 2: 228; Group 3: 300). 135 (17.8%) new diagnoses of coeliac disease were made (21 Group 1; 24 Group 2; 89 Group 3). The sensitivity for detection of endoscopic markers of villous atrophy was significantly higher in both Group 1 (85.7%, p=0.0004) and Group 2 (75%, p=0.005) compared to non-high definition controls (41.6%). There was no significant difference between high definition only and I-Scan groups (p=0.47). In non-high definition endoscopy a missed diagnosis was associated with lesser degrees of villous atrophy (p=0.019) and low tTG titre (p=0.007). CONCLUSIONS: High definition endoscopy with or without I-Scan increases the detection of celiac disease during routine endoscopy. PMID- 26995216 TI - Is genomic selection now a mature technology? PMID- 26995217 TI - Promotion of alleles by genome editing in livestock breeding programmes. PMID- 26995215 TI - Primary Plasma Cell Leukemia: Identity Card 2016. AB - Primary plasma cell leukemia (PPCL) is an aggressive and rare variant of multiple myeloma (MM), characterized by peculiar adverse clinical and biological features. Though the poor outcome of PPCL has been slightly improved by novel treatments during the last 10 years, due to the limited number of available studies in this uncommon disease, optimal therapy remains a classic unmet clinical need. Anyway, in the real-life practice, induction with a bortezomib-based three-drug combination, including dexamethasone and, possibly, lenalidomide, or, alternatively, thalidomide, cyclophosphamide, or doxorubicin, is a reasonable first-line option. This approach may be particularly advisable for patients with adverse cytogenetics, hyperleucocytosis, and rapidly progressive disease, in whom a fast response is required, or for those with suboptimal renal function, where, however, lenalidomide should be used with caution until renal activity is restored. In younger subjects, leukemia/lymphoma-like more intensive regimens, including hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone or continue-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide, may be also combined with bortezomib +/- thalidomide. Treatment must be started immediately after a diagnosis of PPCL is made to avoid the risk of irreversible disease complications and, in such a context, the prevention of tumor lysis syndrome is mandatory. In patients eligible for autologous stem cell transplantation (AuSCT), other alkylating agents, in particular melphalan, should be initially avoided in order to allow adequate collections of CD34+ peripheral blood stem cells (PBSC). A combination of lenalidomide and dexamethasone may be a valuable alternative option to manage older or unfit patients or those with slower disease evolution or with signs of neuropathy, contraindicating the use of bortezomib. Patients not suitable for transplant procedures should continue the treatment, if a response occurs and if tolerated, considering the possibility of a prolonged maintenance therapy. AuSCT should be pursued in all eligible patients less than 65 years old who achieve a significant response after a short course of induction treatment. PBSC collection should reach a threshold of at least 5 * 10(6) CD34+ PBSC/kg using cyclophosphamide plus G-CSF and adding the mobilizing agent plerixafor, if necessary. High-dose melphalan (HDM) (200 or 140 mg/m(2), according to age and renal function) remains the preferable conditioning regimen. A second AuSCT should be always considered, even in patients achieving complete response (CR) after the first AuSCT, as the short progression-free survival (PFS) generally seen in PPCL suggests the persistence of a relevant burden of residual disease; this provides a strong rationale for the use of post-transplantation therapies in PPCL to improve depth of response, to maintain remission, and, possibly, to increase survival, though consolidation and/or maintenance strategies with novel agents, whose efficacy has been well demonstrated in MM, have not been still extensively evaluated in PPCL. The search of a suitable donor should start as soon as possible and an allogeneic stem cell transplant (AlloSCT) with a myeloablative conditioning (MAC) regimen discussed with younger patients responsive to induction therapy and with poor prognostic parameters at diagnosis. A sequence of AuSCT followed by reduced intensity conditioning (RIC) or non myeloablative (NMA) AlloSCT may be considered in selected cases. Salvage therapies for relapsed/refractory disease, especially using new drugs not employed at diagnosis, are sometimes effective in the short term, but a rapid relapse is still generally the rule; AlloSCT in relapsed and eligible patients with sensitive disease after salvage treatments is, therefore, recommended. PMID- 26995218 TI - A combined coalescence gene-dropping tool for evaluating genomic selection in complex scenarios (ms2gs). AB - We present ms2gs, a combined coalescence - gene dropping (i.e. backward-forward) simulator for complex traits. It therefore aims at combining the advantages of both approaches. It is primarily conceived for very short term, recent scenarios such as those that are of interest in animal and plant breeding. It is very flexible in terms of defining QTL architecture and SNP ascertainment bias, and it allows for easy modelling of alternative markers such as RADs. It can use real sequence or chip data or generate molecular polymorphisms via the coalescence. It can generate QTL conditional on extant molecular information, such as low-density genotyping. It models (simplistically) sequence, imputation or genotyping errors. It requires as input both genotypic data in plink or ms formats, and a pedigree that is used to perform the gene dropping. By default, it compares accuracy for BLUP, SNP ascertained data, sequence, and causal SNPs. It employs VanRaden's linear (GBLUP) and nonlinear method for incorporating molecular information. To illustrate the program, we present a small application in a half-sib population and a multiparental (MAGIC) cross. The program, manual and examples are available at https://github.com/mperezenciso/ms2gs. PMID- 26995219 TI - Comparative study on the in vitro replication and genomic variability of Argentinean field isolates of bovine herpesvirus type 4 (BoHV-4). AB - Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus, belonging to the Rhadinovirus genus, which is increasingly associated with various problems of the reproductive tract of cattle. In Argentina, analysis of BoHV-4 strains isolated from cervico-vaginal mucus of aborted cows revealed a high genetic divergence among strains, which could be classified in three different groups: Genotype 1 comprises Movar-like strains (European prototype), Genotype 2 includes DN599-like strains (American prototype) and Genotype 3 corresponds to a novel genotype group. Understanding the replication behavior in cell cultures and the molecular characteristics of this pathogen of cattle is critical for the rational design of in vitro experiments. The aim of this work was to quantitatively evaluate the replication properties of different Argentinean BoHV-4 strains and to characterize their phylogenetic relationships. Significant differences were evident among the virus titers of the different BoHV-4 isolates in vitro. The most conserved gene was the major capsid protein (ORF25). The glycoprotein B (gB), glycoprotein H (gH), and thymidine kinsase (TK) genes displayed both synonymous and non-synonymous substitutions, with the highest diversity observed for gB, which displayed amino acid substitutions in 24 out of the 178 positions examined. Strains 09/759, 12/512, and 07/568 presented a deletion encompassing amino acid position 27 to 35, whereas strains 07/435 and 09/227 had a deletion from position 28 to 35. Two strains, 07/435 and 09/227, also displayed the highest divergence compared to the other strains analyzed. This study provides information about the in vitro replication and behavior of nine field isolates of BoHV-4. These findings are relevant since available information on the in vitro growth characteristics of BoHV-4 strains is scarce. The results from this study may also be useful for establishing comparisons with other related viruses. PMID- 26995221 TI - Discovery of a novel Parvovirinae virus, porcine parvovirus 7, by metagenomic sequencing of porcine rectal swabs. AB - Parvoviruses are a diverse group of viruses containing some of the smallest known species that are capable of infecting a wide range of animals. Metagenomic sequencing of pooled rectal swabs from adult pigs identified a 4103-bp contig consisting of two major open reading frames encoding proteins of 672 and 469 amino acids (aa) in length. BLASTP analysis of the 672-aa protein found 42.4 % identity to fruit bat (Eidolon helvum) parvovirus 2 (EhPV2) and 37.9 % to turkey parvovirus (TuPV) TP1-2012/HUN NS1 proteins. The 469-aa protein had no significant similarity to known proteins. Genetic and phylogenetic analyses suggest that PPV7, EhPV2, and TuPV represent a novel genus in the family Parvoviridae. Quantitative PCR screening of 182 porcine diagnostic samples found a total of 16 positives (8.6 %). Together, these data suggest that PPV7 is a highly divergent novel parvovirus prevalent within the US swine. PMID- 26995220 TI - Merkel cell polyomavirus in Merkel cell carcinogenesis: small T antigen-mediates c-Jun phosphorylation. AB - Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer associated with the Merkel cell polyomavirus (MCPyV). The MCPyV genome, which is clonally integrated in the majority of MCCs, encodes the regulatory small T (sT) antigen. Previously, reports have established MCPyV sT antigen as a potent oncogene capable of inducing cell transformation. In the current study, we demonstrate a distinct role for c-Jun hyperactivation in MCPyV sT antigen pathogenesis. As MCPyV sT antigen's association with aggressive cancer growth has been previously established, this finding may represent a potential therapeutic target for the treatment of MCCs. PMID- 26995222 TI - Major mutation events in structural genes of peste des petits ruminants virus through serial passages in vitro. AB - Peste des petits ruminants (PPR) is an highly contagious disease of small ruminants, and caused by peste des petits ruminants virus (PPRV), a member of the genus Morbillivirus in the family Paramyxoviridae. The first outbreak of PPR in China was officially reported in July 2007, when a PPRV strain was successfully isolated from a sick goat in Tibet, followed by sequencing at a full-genome level (China/Tibet/Geg/07-30, GenBank: FJ905304.1). To date, this isolate has been virulently attenuated by more than 90 serial passages in Vero-Dog-SLAM cells at our laboratory. In this study, a total of nine strains by serial passages (namely the 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th, and 90th passages) were chosen for sequencing of six structural genes in PPRV. The sequence analysis showed that mutation rates in all viral genes were relatively low, and only a few identical mutations within certain genes were stably maintained after an earlier passage, perhaps indicating a predominance of mutants after such a passage. PMID- 26995223 TI - Tracking metastatic breast cancer: the future of biology in biosensors. AB - Circulating tumour cells associated with breast cancer (brCTCs) represent cells that have the capability to establish aggressive secondary metastatic tumours. The isolation and characterization of CTCs from blood in a single device is the future of oncology diagnosis and treatment. The methods of enrichment of CTCs have primarily utilized simple biological interactions with bimodal reporting with biased high purity and low numbers or low purity and high background. In this review, we will discuss the advances in microfluidics that has allowed the use of more complex selection criteria and biological methods to identify CTC populations. We will also discuss a potential new method of selection based on the response of the oncogenic DNA repair pathways within brCTCs. This method would allow insight into not only the oncogenic signalling at play but the chemoresistance mechanisms that could guide future therapeutic intervention at any stage of disease progression. PMID- 26995224 TI - Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience. AB - Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5 fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan-Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1-5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC. PMID- 26995225 TI - A third-person perspective on co-speech action gestures in Parkinson's disease. AB - A combination of impaired motor and cognitive function in Parkinson's disease (PD) can impact on language and communication, with patients exhibiting a particular difficulty processing action verbs. Co-speech gestures embody a link between action and language and contribute significantly to communication in healthy people. Here, we investigated how co-speech gestures depicting actions are affected in PD, in particular with respect to the visual perspective-or the viewpoint - they depict. Gestures are closely related to mental imagery and motor simulations, but people with PD may be impaired in the way they simulate actions from a first-person perspective and may compensate for this by relying more on third-person visual features. We analysed the action-depicting gestures produced by mild-moderate PD patients and age-matched controls on an action description task and examined the relationship between gesture viewpoint, action naming, and performance on an action observation task (weight judgement). Healthy controls produced the majority of their action gestures from a first-person perspective, whereas PD patients produced a greater proportion of gestures produced from a third-person perspective. We propose that this reflects a compensatory reliance on third-person visual features in the simulation of actions in PD. Performance was also impaired in action naming and weight judgement, although this was unrelated to gesture viewpoint. Our findings provide a more comprehensive understanding of how action-language impairments in PD impact on action communication, on the cognitive underpinnings of this impairment, as well as elucidating the role of action simulation in gesture production. PMID- 26995226 TI - Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach. AB - Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. PMID- 26995227 TI - Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells. AB - Aluminum (Al), a non-essential element, is ubiquitous in industrialized societies. Whereas adult intake is estimated between 3 and 12 mg/day according to dietary aluminum studies conducted in many countries, it is not known if aluminum may have a toxic effect on intestinal epithelium. The aim of this work was to evaluate the cytotoxicity and RNA expression patterns induced in HT-29 cells by aluminum. Both classical toxicological methods and a global transcriptomic approach were used. Cytotoxicity determined by MTT assay showed a time and dose dependent decrease of cell viability in aluminum treated cells compared to control cells. Cell cycle analysis by flow cytometry revealed that aluminum induced accumulation of cells in phase G0/G1, associated with a decrease in the proportion of cells in S and G2/M phases. Aluminum led to apoptosis as evidenced by nuclear morphology changes and mitochondrial membrane perturbations, and induced reactive oxygen species generation. Transcriptomic pattern argued in favor of pro-tumorigenic and pro-inflammatory effects of aluminum in intestinal epithelial cells. These results highlight several pathways by which aluminum has a disturbing impact on intestinal epithelial cells, supporting that the effects of aluminum on intestine warrants further investigation. PMID- 26995228 TI - In vivo relevant mixed urolithins and ellagic acid inhibit phenotypic and molecular colon cancer stem cell features: A new potentiality for ellagitannin metabolites against cancer. AB - Colon cancer stem cells (CSCs) offer a novel paradigm for colorectal cancer (CRC) treatment and dietary polyphenols may contribute to battle these cells. Specifically, polyphenol-derived colon metabolites have the potential to interact with and affect colon CSCs. We herein report the effects against colon CSCs of two mixtures of ellagitannin (ET) metabolites, ellagic acid (EA) and the gut microbiota-derived urolithins (Uro) at concentrations detected in the human colon tissues following the intake of ET-containing products (pomegranate, walnuts). These mixtures reduce phenotypic and molecular features in two models of colon CSCs: Caco-2 cells and primary tumour cells from a patient with CRC. The mixture containing mostly Uro-A (85% Uro-A, 10% Uro-C, 5% EA) was most effective at inhibiting the number and size of colonospheres and aldehyde dehydrogenase activity (ALDH, a marker of chemoresistance) whereas the mixture containing less Uro-A but IsoUro-A and Uro-B (30% Uro-A, 50% IsoUro-A, 10% Uro-B, 5% Uro-C, 5% EA) had some effects on the number and size of colonospheres but not on ALDH. These data support a role for polyphenols metabolites in the control of colon cancer chemoresistance and relapse and encourage the research on the effects of polyphenols against CSCs. PMID- 26995229 TI - Effects of voluntary/involuntary retirement on their own and spouses' depressive symptoms. AB - OBJECTIVES: The aim of our study was to elucidate the effect of voluntary/involuntary retirement on individuals' and spouses' depressive symptoms using the Korean Longitudinal Study of Aging (KLoSA). METHODS: This study used a sample derived from the first- to fourth-wave cohort datasets of KLoSA, which was conducted in 2006, 2008, 2010, and 2012. After applying inclusion and exclusion criteria, we analyzed a total of 6706 subjects. Information about employment status, the short-form Center for Epidemiological Studies-Depression scale, and covariates (age, property, household income, perceived health status and medical disability) were obtained. Cox proportional hazards models were used to evaluate the effects of voluntary/involuntary retirement on individuals' and spouses' depressive symptoms. RESULTS: The voluntary/involuntary retirement groups showed significantly more depressive symptoms than the working group in wave 1-4, and the same results were revealed in the spouse's retirement and job loss measures. The hazard ratios of depressive symptoms of the voluntary/involuntary retirement groups were 1.26-1.31 during the 6year follow-up period. The wives' risk of depressive symptoms was also significantly increased if their husbands voluntarily retired (HR=1.35, 95% CI=1.10-1.65). CONCLUSION: During the 6year follow-up study, Voluntary/involuntary retirement increased the risk of depressive symptoms in a Korean elderly population. Furthermore, husbands' voluntary retirement increased wives' risk of depressive symptoms. PMID- 26995230 TI - Assessment and associated features of prolonged grief disorder among Chinese bereaved individuals. AB - BACKGROUND: Most research on the assessment and characteristics of prolonged grief disorder (PGD) has been conducted in Western bereaved samples. Limited information about PGD in Chinese samples exists. This study aims to validate the Chinese version of the Inventory of Complicated grief (ICG), examine the distinctiveness of PGD symptoms from symptoms of bereavement-related depression and anxiety, and explore the prevalence of PGD in a Chinese sample. METHODS: Responses from 1358 bereaved Chinese adults were collected through an on-line survey. They completed the Chinese version of ICG and a questionnaire measuring depression and anxiety symptoms. RESULTS: The findings indicate that Chinese ICG has sound validity and high internal consistency. The ICG cut-off score for PGD "caseness"in this large Chinese sample was 48. The distinctiveness of PGD symptoms from those of depression and anxiety was supported by the results of the confirmatory factor analysis and the fact that PGD occurred in isolation in the studied sample. The prevalence of PGD was13.9%. CONCLUSION: ICG is a valid instrument for use in the Chinese context. Several key characteristics of PGD in Chinese, either different from or comparable to findings in Western samples, may stimulate further research and clinical interest in the concept by providing empirical evidence from an large and influential Eastern country. PMID- 26995231 TI - Childhood traumatic events and types of auditory verbal hallucinations in first episode schizophrenia patients. AB - OBJECTIVE: Evidence is accumulating that childhood trauma might be associated with higher severity of positive symptoms in patients with psychosis and higher incidence of psychotic experiences in non-clinical populations. However, it remains unknown whether the history of childhood trauma might be associated with particular types of auditory verbal hallucinations (AVH). METHOD: We assessed childhood trauma using the Early Trauma Inventory Self-Report - Short Form (ETISR SF) in 94 first-episode schizophrenia (FES) patients. Lifetime psychopathology was evaluated using the Operational Criteria for Psychotic Illness (OPCRIT) checklist, while symptoms on the day of assessment were examined using the Positive and Negative Syndrome Scale (PANSS). Based on ETISR-SF, patients were divided into those with and without the history of childhood trauma: FES(+) and FES(-) patients. RESULTS: FES(+) patients had significantly higher total number of AVH types and Schneiderian first-rank AVH as well as significantly higher PANSS P3 item score (hallucinatory behavior) in comparison with FES(-) patients. They experienced significantly more frequently third person AVH and abusive/accusatory/persecutory voices. These differences remained significant after controlling for education, PANSS depression factor score and chlorpromazine equivalent. Linear regression analysis revealed that the total number of AVH types was predicted by sexual abuse score after controlling for above mentioned confounders. This effect was significant only in females. CONCLUSION: Our results indicate that the history of childhood trauma, especially sexual abuse, is associated with higher number AVH in females but not in males. Third person AVH and abusive/accusatory/persecutory voices, representing Schneiderian first-rank symptoms, might be particularly related to childhood traumatic events. PMID- 26995232 TI - Validity of the Brief Dyadic Scale of Expressed Emotion in Adolescents. AB - PURPOSE: Perceived expressed emotion is a valuable predictor of clinical outcome in psychiatric and community samples, but its assessment is limited to few instruments. A recent development to briefly assess expressed emotion from the patient's perspective is the 14-item Brief Dyadic Scale of Expressed Emotion (BDSEE). Although psychometric properties of the BDSEE have been provided for adult eating disorders, validity for adolescents is still lacking. In this study, BDSEE's factorial, convergent, and divergent validity was tested in an adolescent sample with binge-eating disorder and a matched community sample. METHODS: For validation, well-established self- and mother-report questionnaires and adolescent's Five Minute Speech Sample were used. RESULTS: Confirmatory factor analysis on the German BDSEE replicated the proposed three-factor structure in adolescents. BDSEE's convergent validity with the Five Minute Speech Sample and construct-related questionnaires was shown. Divergent validity was documented with BDSEE subscales being unrelated to socio-demographic and clinical characteristics. Further, BDSEE subscales were unrelated to measures of maternal distress. CONCLUSIONS: While the results underline that the BDSEE is a valid self report measure for assessing perceived expressed emotion in adolescents with and without binge-eating disorder, the evaluation of its predictive validity is still in need. PMID- 26995233 TI - Motivational deficits in major depressive disorder: Cross-sectional and longitudinal relationships with functional impairment and subjective well-being. AB - BACKGROUND: Many individuals with major depressive disorder present with prominent motivational deficits; however, the effect of these symptoms on functional outcomes in the illness remains unclear. METHOD: Individuals with major depression who participated in the Sequenced Treatment Alternatives to Relieve Depression study were included in the present investigation (N=1563). Motivational deficits were evaluated using a derived measure from the Hamilton Depression Rating Scale, while functioning was assessed using the Work and Social Adjustment Scale. Subjective outcomes were also evaluated using the Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: After treatment with citalopram, over 70% of participants continued to experience some degree of motivational deficits. These deficits were significantly associated with greater functional impairments both globally and in each domain of functioning evaluated. These symptoms were also linked to worse subjective outcomes such as overall life satisfaction and quality of life. Change in the severity of motivational deficits over time was significantly linked with changes in outcome. Motivational deficits continued to demonstrate a significant association with outcomes, even after controlling for potentially confounding variables such as duration of depressive episode and severity of other depressive symptoms. CONCLUSIONS: Motivational deficits are significantly linked to the functional impairment present in many people with major depression, just as they are in other psychiatric illnesses such as schizophrenia. A greater understanding of the underlying mechanisms of these motivational deficits in particular, beyond other depressive symptoms, is critical to the development of strategies aimed at enhancing functional recovery and improved subjective well-being. PMID- 26995234 TI - An initial investigation of abnormal bodily phenomena in subjects at ultra high risk for psychosis: Their prevalence and clinical implications. AB - BACKGROUND: Contemporary phenomenological research has considered abnormal bodily phenomena (ABP) to be a phenotypic trait of subjects with schizophrenia in their first psychotic episode. Yet the prevalence of ABP and their clinical significance in subjects at Ultra High Risk (UHR) of psychosis remain unidentified. This study is an exploratory investigation of ABP in UHR subjects and matched healthy controls (HCs) examining their relation to clinical features and basic self-disturbances. METHODS: A sample of 26 UHR and 14 HC subjects from three prodromal and early intervention clinics in South London, West London and Cambridge was assessed with the Abnormal Bodily Phenomena questionnaire (ABPq), Comprehensive Assessment of At-Risk Mental States (CAARMS), the Positive and Negative Syndrome Scale (PANSS), the Social and Occupational Functioning Assessment Scale (SOFAS) and the Examination of Anomalous Self Experiences (EASE) checklist. RESULTS: In our sample ABP occurred in 73.1% of UHR subjects and prominent ABP (proABP) were referred in 53.8% of them. No HC subject reported ABP. The UHR group with proABP had lower CAARMS total score (t=-9.265, p=0.006). There were no differences in PANSS total score (t=-1.235, p=0.277), SOFAS score (H(2) 22.27, p=0.666) and EASE total scores (z=8.565, adjusted p=0.185) in the UHR subjects with prominent ABP versus those that did not. DISCUSSION: This initial investigation suggests that ABP could be a prevalent phenotypic feature of UHR subjects. PMID- 26995235 TI - Prevalence and symptomatic correlates of interpersonal trauma in South Korean outpatients with major depressive disorder. AB - BACKGROUND: There is growing evidence that exposure to severe interpersonal trauma (IPT) has a pivotal role in the development and manifestation of depression. However, it is not clearly understood whether patients with major depressive disorder (MDD) have specifically increased prevalence of IPT than other non-interpersonal traumatic events and whether those with IPT have unique symptom profile within depressed groups. In this study, we investigated the prevalence of past traumatic events and symptomatic features of treatment-seeking outpatients with MDD. METHODS: A consecutive sample of 111 South Korean outpatients with MDD was recruited on their first visit to a psychiatric department of a university-affiliated hospital. Participants completed the Life Events Checklist (LEC), the Symptom Checklist-90-Revised (SCL-90-R), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Dissociative Experience Scale (DES) and Impact of Event Scale-Revised (IES-R). The prevalence of past traumatic events on LEC was compared to medical outpatients. RESULTS: Compared to medical outpatients, MDD patients had significantly higher rates of IPT (physical and sexual) but not other traumatic events of non-interpersonal origin such as accidents or disaster. Compared to MDD patients without IPT (n=44, 40%), those with IPT (n=67, 60%) had higher subscale scores on hostility in SCL 90-R, as well as greater depressive and post-traumatic symptoms. However, multivariate analysis revealed that the best model to discriminate those with IPT was interaction of depressive and posttraumatic symptoms. LIMITATIONS: Limitations include sample characteristics (treatment-seeking outpatients) and possible effects of comorbid conditions, which were not investigated. CONCLUSIONS: Clinicians managing individuals with depressive disorder need to include the assessment of lifetime IPT and its impact on presenting symptoms. PMID- 26995236 TI - Comparing how co-morbid depression affects individual domains of functioning and life satisfaction in schizophrenia. AB - OBJECTIVE: Depression in schizophrenia is often associated with reduced life satisfaction. Yet, it is not clear how depression influences different functioning domains. The relative impact across objective and subjective quality of life (QOL) has also not been clearly compared. This study sought to examine the differences in individual QOL indicators between schizophrenia patients with and without co-morbid depression. This was completed separately for objective and subjective QOL. METHOD: 57 patients with schizophrenia/schizoaffective disorder were classified into groups with (DP: N=31, M=45.81, SD=10.29) and without depression (NDP: N=26, M=40.54, SD=11.00) using MADRS scores. Objective and subjective QOL was assessed using Lehman's (1988) QOL Interview using five domains: daily activities and functioning, family relations, social relations, safety and health. z-scores were created for these domains (objective and subjective) based on responses from 44 healthy controls (M=39.80, SD=13.94). RESULTS: Objectively, DP patients had significantly reduced social interaction frequency compared to HCs. Subjectively, DP patients had significantly poorer scores than HCs on all five domains, and additionally reported poorer satisfaction with daily activities and health compared with the NDP group. CONCLUSIONS: Presence of depression in schizophrenia results in reduced self reported life satisfaction across a broad spectrum of QOL domains. Objectively, depression resulted in decreased interactions with friends and peers, i.e. greater social isolation. The findings support the need to continue developing and implementing peer support groups in schizophrenia, a challenging task especially in the face of depression. More broadly, the assessment of depression in other illnesses is recommended. PMID- 26995237 TI - Social contacts and loneliness in people with psychotic and mood disorders. AB - BACKGROUND: Social relations can be measured through: a) objective indicators, i.e. the number of social contacts in a given time interval or b) subjective indicators, i.e. feelings of loneliness. Comparing subjective and objective indicators in patients with psychotic and mood disorders may help to understand whether diagnosis-specific interventions should be designed for increasing their social relations. In this study we assessed social contacts outside home, work environments and mental health services, which may be increased by these interventions. We also explored feelings of loneliness which could influence readiness of patients to participate in interventions. METHODS: 100 patients in outpatient mental health care were asked to: a) list their social contacts; b) report their feelings of loneliness on a validated five point Likert scale. Multiple logistic regression models were used to test associations of diagnostic categories with: a) having more than one social contact in the previous week; b) reporting at least moderate feelings of loneliness. RESULTS: Patients had on average 1.7 (SD=1.7) social contacts in the previous week (median=1.0); 77 patients reported at least moderate feelings of loneliness. Patients with psychotic disorders (n=30) showed a statistical trend towards having just one or no contacts in the week before the assessment (Odds ratio, OR=2.246, p=.087). Patients with mood disorders were more likely to report at least moderate feelings of loneliness (OR=2.798; p<.05). CONCLUSIONS: Patients with psychotic disorders, compared to those with mood disorders, may be less likely to report feeling lonely although they tend to have less social contacts. Strategies to enhance social relations of people with psychotic disorders may include approaches to increase patients' drive to establish new social contacts and to emotionally support them in this process. PMID- 26995238 TI - Validation of the NetSCID: an automated web-based adaptive version of the SCID. AB - The present study developed and validated a configurable, adaptive, web-based version of the Structured Clinical Interview for DSM, the NetSCID. The validation included 24 clinicians who administered the SCID and 230 participants who completed the paper SCID and/or the NetSCID. Data-entry errors, branching errors, and clinician satisfaction were quantified. Relative to the paper SCID, the NetSCID resulted in far fewer data-entry and branching errors. Clinicians 'preferred' using the NetSCID and found that the NetSCID was easier to administer. PMID- 26995239 TI - Comparative analysis of affective temperament in patients with difficult-to-treat and easy-to-treat major depression and bipolar disorder: Possible application in clinical settings. AB - BACKGROUND: Difficult-to-treat major depressive disorder (MDD-DT), which involves antidepressant refractoriness or antidepressant-related adverse psychiatric effects, is bipolar in nature; therefore, it may share common temperamental features with bipolar disorder. To examine this hypothesis, affective temperament was compared between MDD-DT, easy-to-treat major depressive disorder (MDD-ET), and bipolar disorder. METHODS: Affective temperament was measured in 320 patients (69, 56, and 195 with MDD-ET, MDD-DT, and bipolar disorder, respectively) using the self-rated questionnaire version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A), with between-group differences examined using multiple logistic regression analysis controlling for confounders. Optimal cut-off points for TEMPS-A scores to discriminate between diagnostic groups were determined using receiver-operating characteristic analysis. RESULTS: Of the five temperamental domains, the mode for cyclothymic temperament score was highest, followed by those of bipolar disorder, MDD-DT, and MDD-ET. The cyclothymic temperament score discriminated significantly between bipolar disorder and MDD-DT (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.04-1.20, p=0.0022), MDD DT and MDD-ET (OR: 1.15, 95% CI: 1.01-1.31, p=0.0334), and bipolar and major depressive disorders (OR: 1.17, 95% CI: 1.07-1.28, p=0.0003). Optimal cut-off points for the cyclothymic temperament scores to discriminate between bipolar disorder and major depressive disorder and MDD-DT and MDD-ET were 9 (sensitivity: 64.6%, specificity: 76.0%) and 6 (66.1%, 62.3%), respectively. CONCLUSIONS: MDD DT has a quantitatively stronger bipolar temperamental feature, cyclothymic temperament, relative to that of MDD-ET. Cut-off points determined in this study could be clinically helpful. Because of our study design, longitudinal changes in temperamental scores during treatment cannot be fully excluded. PMID- 26995240 TI - Eating disorders and eating pathology in young adult and adult patients with ESSENCE. AB - BACKGROUND: Little is known about the prevalence and incidence of traditional eating disorders (EDs, e.g., anorexia nervosa (AN), bulimia nervosa and binge eating disorder (BED)) in individuals with childhood onset neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). The aim of the present study was to examine the prevalence of EDs and eating pathology in young adults and adults with ADHD and/or ASD, and to investigate the relationship between EDs and associated symptoms, on the one hand, and other psychiatric disorders, intelligence, and BMI, on the other hand, in this population. METHODS: In an outpatient setting, 228 consecutively referred adults were neuropsychiatrically evaluated and assessed with regard to intelligence (WAIS-III), psychiatric comorbidities (SCID I), personality disorders (SCID-II), eating disorders (SCID-I) and eating pathology (Eating Attitudes Test (EAT)). RESULTS: For the entire sample, a total of 18 individuals (7.9%) had a current or previous eating disorder, with AN and BED being the most frequent. The male:female ratio was 1:2.5. According to EAT, 10.1% of the individuals scored within the range of severely disturbed eating behavior, and 13% moderately disturbed eating behavior. Individuals with ADHD more often affirmed eating pathology such as focusing on thoughts of calories and body dissatisfaction compared to individuals with ASD. CONCLUSIONS: Eating disorder symptomatology seems to be overrepresented in adults with neuropsychiatric disorders compared with the general population. The gender ratio for EDs in adults with neuropsychiatric disorders is not nearly as skewed as in the general population. PMID- 26995241 TI - Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history. AB - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been independently related to bipolar disorder (BD) and factors associated with suicidal risk. The aim of our study was to explore the relationship between NLR and suicide risk in euthymic BD patients. We also sought to propose a model of interaction between NLR and stress-diathesis factors, leading to suicidal risk in BD. METHODS: The study group consisted of 83 patients diagnosed with BD (36 suicide attempters; 47 suicide non-attempters), compared to the healthy control group (n=73) and matched according to age, gender, and body mass index (BMI). NLR was measured according to the complete blood count. Mood symptoms have been assessed by Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale. Early trauma and acute stress were evaluated by Early Trauma Inventory Self Report-Short Form and List of Threatening Experiences Questionnaire, respectively. Suicide risk has been assessed by Suicide Behaviors Questionnaire-Revised (SBQ-R). RESULTS: Significant correlation was found between NLR and SBQ-R score. The main effects of suicide attempts on NLR, after covarying for confounders, were observed, indicating increased NLR in BD suicide attempters compared to healthy controls. We found significant moderatory effects of family history on NLR relationship to suicidal risk, with NLR being significant positive predictor of suicidal risk only in the patients with positive family history of suicide attempts. CONCLUSIONS: The results suggest an enhancing effect of positive family history of suicide attempts on predictive effect of NLR on suicide risk. Our data support the idea that immune markers can predict suicide attempt risk in BD, but only in the subpopulation of BD patients with family history of suicide attempts. This could lead to prevention in suicide behavior in the patient population at particular risk of suicide. PMID- 26995242 TI - Further psychometric properties of the Yale-Brown Obsessive Compulsive Scale - Second Edition. AB - The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a widely used clinician rated measure for assessing obsessive-compulsive symptoms. Although numerous studies have supported its reliability and validity, improved phenomenological understanding of obsessive-compulsive disorder (OCD) suggests the need for modifications to item content, structure, and scoring. Consequently, the Yale Brown Obsessive Compulsive Scale - Second Edition (Y-BOCS-II) was developed. While the Y-BOCS-II shows initial promise, minimal data exist in examining the psychometric properties of the Y-BOCS-II English version. In response, the Y-BOCS II was administered to 61 adult patients with a principal diagnosis of obsessive compulsive disorder. The internal consistency for the scores on the Obsession Severity (alpha=.83), Compulsion Severity (alpha=.75), and Total Severity (alpha=.86) scales were acceptable to good. The inter-rater reliability for the severity scale scores was excellent (ICC=.97-99) and the test-retest reliability was acceptable (r=.64-81). Strong convergent validity was observed between the Y BOCS-II Total Severity scale and other measures of obsessive-compulsive symptom severity and related impairment. Good divergent validity was supported by non significant correlations between the Total Severity score and measures of anxiety and impulsiveness, though a moderate correlation was observed with depressive symptoms. Collectively, the Y-BOCS-II generally possesses sound psychometric properties and appears to be a viable alternative to the original Y-BOCS. PMID- 26995243 TI - Associations between negative affect and binge/purge behaviors in women with anorexia nervosa: Considering the role of negative urgency. AB - OBJECTIVE: Evidence implicates negative affect in the occurrence of binge/purge behaviors, although the extent to which theoretically relevant individual difference variables may impact this association remains unclear. Negative urgency, the dispositional tendency to engage in rash action when experiencing negative affect, is a unique facet of impulsivity that may play a key role. Moreover, it was hypothesized that women with anorexia nervosa (AN) who are higher on measures of negative urgency, relative to those lower on negative urgency, would exhibit: 1) greater binge eating and purging frequencies on high negative affect days, and 2) a greater change in negative affect prior to and following binge eating and purging episodes. METHOD: Women with AN (n=82) completed a self-report measure of negative urgency and a 2-week ecological momentary assessment protocol in which they recorded binge eating, purging, and negative affect ratings. RESULTS: Women with higher levels of negative urgency exhibited a greater frequency of binge eating and purging; however, in comparison to women low on negative urgency, they: 1) were more likely to binge eat on days corresponding with low-to-moderate negative affect (similar rates of binge eating were observed on high negative affect days), and 2) displayed substantially elevated levels of negative affect across time, and thus, smaller degrees of change in negative affect prior to and following binge eating and purging episodes. DISCUSSION: Negative urgency underlies individual differences in the daily experience of negative affect. Women with AN who are high on negative urgency may have an increased propensity for binge eating and purging via a relatively persistent and heightened state of negative emotions. PMID- 26995245 TI - At the core of eating disorders: Overvaluation, social rank, self-criticism and shame in anorexia, bulimia and binge eating disorder. AB - This study examined the similarities and differences in eating psychopathology symptoms, overvaluation of body shape, weight and eating, general psychopathology, social comparison, self-criticism and shame, between AN, BN and BED patients. Also, the mediator effect of self-criticism and social comparison on the association between overvaluation and shame, was tested. Participants were 119 patients (34 AN, 34 BN and 51 BED) diagnosed through the Eating Disorder Examination. Results indicated that BED patients are older and present higher BMI. The groups differed regarding eating disorders' symptomatology, but no significant differences were observed in overvaluation, self-criticism, shame and overall psychopathology symptoms. The path model confirmed that overvaluation has a significant indirect association with shame, which is mediated by severe self criticism and negative social comparisons. The model was fond to be invariant between the clinical groups. These findings contribute for the understanding of the common processes that feed the perpetual cycle of eating psychopathology. Thus, these data have potential implications for transdiagnostic approaches to treatment. PMID- 26995244 TI - Executive function in fibromyalgia: Comparing subjective and objective measures. AB - BACKGROUND: There is evidence to suggest the existence of an executive dysfunction in people diagnosed with fibromyalgia, although there are certain inconsistencies between studies. Here, we aim to compare executive performance between patients with fibromyalgia and a control group by using subjective and objective cognitive tests, analyzing the influence of patient mood on the results obtained, and studying associations between the two measures. METHOD: 82 patients diagnosed with fibromyalgia and 42 healthy controls, matched by age and years of education, were assessed using the Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) as a subjective measure of executive functioning. A selection of objective cognitive tests were also used to measure a series of executive functions and to identify symptoms of depression and anxiety. RESULTS: Patients with fibromyalgia perceived greater difficulties than the control group on all of the BRIEF-A scales. However, after adjustments were made for depression and anxiety the only differences that remained were those associated with the working memory scale and the Metacognition and Global Executive Composite index. In the case of the objective cognitive tests, a significantly worse overall performance was evidenced for the fibromyalgia patients. However, this also disappeared when adjustments were made for depression and anxiety. After this adjustment, fibromyalgia patients only performed significantly worse for the interference effect in the Stroop Test. Although there were no significant associations between most of the objective cognitive tests and the BRIEF-A scales, depression and anxiety exhibited strong associations with almost all of the BRIEF-A scales and with several of the objective cognitive tests. CONCLUSIONS: Patients with fibromyalgia showed executive dysfunction in subjective and objective measures, although most of this impairment was associated with mood disturbances. Exceptions to this general rule were observed in the impairment of working memory evidenced on the BRIEF-A scale and the inhibition impairment exhibited by the interference effect from the Stroop Test. The two types of measurement provide different yet complementary information. PMID- 26995246 TI - The effect of suicide attempts on suicide ideation by family members in fast developed country, Korea. AB - INTRODUCTION: Suicide is a leading cause of death globally and is one of the most exigent health problems, especially in Korea. Individuals think about suicide first before they attempt and possibly complete suicide. If attempted or completed suicide affects suicidal ideation by family members or close individuals, suicide could spread like an infectious disease. We hypothesized that a suicide attempt by a family member could affect suicidal ideation. We analyzed the association between suicidal ideation and previous suicide attempts by family members. METHODS: This study used data from the fourth and fifth Korea National Health and Nutrition Examination Survey (2007-2012). The independent variable of interest is the existence of a cohabitating family member who previously attempted suicide. The dependent variable is self-reported suicide ideation during past year. The data analysis was conducted using the chi-square test and survey logistic regression. RESULTS: Suicidal ideation was reported by 14.3% of the total study population (9.5% of males, 19.0% of females), by 23.6% (22.8% of males, 31.3% of females) of individuals with a family member who attempted suicide, and by 14.1% (9.3% of males, 19.9% of females) of individuals without a family member who attempted suicide. Individuals with a family member who attempted suicide had increased odds of suicidal ideation compared with those without a family member who attempted suicide (odds ratio=2.09, 95% CI 1.48-2.49, p<0.001). CONCLUSIONS: To prevent suicide spreading like an infectious disease, government and policy makers should give thought and consideration to individuals with a family member who attempts suicide. PMID- 26995247 TI - Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers. AB - Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]>=15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score>=8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to standard anti-anxiety treatments, and it may represent a novel transdiagnostic target for treatment intervention in this population. Anxiety and global function improved in a small trial of a brief, manualized, attachment-focused psychodynamic psychotherapy, potentially supporting the clinical relevance of attachment dysfunction in this sample. The large decrease in oxytocin levels with treatment, although not statistically significant in this very small sample, suggests the need for further study of oxytocin as a putative biomarker or mediator of SA response. These pilot data generate testable hypotheses supporting an attachment domain underlying treatment resistant anxiety, and new treatment strategies. PMID- 26995248 TI - Clinical correlates of sustained response to individual drugs used in naturalistic treatment of patients with bipolar disorder. AB - OBJECTIVE: To report use and treatment success rates of medications for bipolar disorder as a function of patients' clinical characteristics. METHOD: Outpatients with bipolar illness diagnosed by SCID were rated by research assistants on the NIMH-LCM and those who had an good response for at least 6months (much or very much improved on the CGI-BP) were considered responders (treatment "success"). Clinical characteristics associated with treatment response in the literature were examined for how often a drug was in a successful regimen when a given characteristic was either present or absent. RESULTS: Lithium was less successful in those with histories of rapid cycling, substance abuse, or (surprisingly) a positive parental history of mood disorders. Valproate was less successful in those with >=20 prior episodes. Lamotrigine (LTG) was less successful in those with a parental history of mood disorders or in BP-I compared to BP-II disorder. Antidepressants (ADs) had low success rates, especially in those with a history of anxiety disorders. Benzodiazepines had low success rates in those with child abuse, substance use, or >=20 episodes. Atypical antipsychotics were less successful in the presence of rapid cycling, >=20 prior episodes, or a greater number of poor prognosis factors. CONCLUSION: Success rates reflect medications used in combination with an average of two other drugs during naturalistic treatment and thus should be considered exploratory. However, the low long-term success rates of drugs (even when used in combination with others) that occurred in the presence of many very common clinical characteristics of bipolar illness speak to the need for the development of alternative treatment strategies. PMID- 26995249 TI - Relapses and recurrences of catatonia: 30-case analysis and literature review. AB - OBJECTIVE: Relieving catatonia helps identify the underlying etiology and its treatment. However, catatonia may reemerge after some time, but there are few data on the relapses and recurrences of catatonia. We aimed to investigate the characteristics of patients with relapses or recurrences of catatonia as well as the efficacy of the lorazepam-diazepam protocol on them. METHODS: Patients with catatonia who had more than one episode of catatonia and were treated with the lorazepam-diazepam protocol were identified. Their medical charts were reviewed, and interview was conducted. RESULTS: Thirty patients were identified. Nineteen (63.3%) were diagnosed with schizophrenia, five (16.7%) with major depressive disorder, two (6.7%) with bipolar disorder, and four (13.3%) with general medical conditions. In the 68 relapses and relapses the lorazepam-diazepam protocol was used, full response was reported in 54 (79.4%) of them. Twelve of 19 (63.2%) patients with schizophrenia were treated with clozapine. Twenty (66.7%) out of 30 patients were maintained on oral lorazepam by the time of discharge. Literature review showed similar prevalence of schizophrenia in patients with more than one episode of catatonia, and a wide variety of treatment options. CONCLUSION: The lorazepam-diazepam protocol was mostly effective in managing relapses and recurrences of catatonia. Maintenance clozapine and oral lorazepam were beneficial in a significant number of patients. PMID- 26995250 TI - Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome: Preliminary evidence of divergence between objective indices and subjective perceptions. AB - BACKGROUND: Neurocognitive difficulties are commonly reported by patients suffering from chronic fatigue syndrome (CFS). Moderate improvements from 'best practice' therapy are promising, but to date reported efficacy is based entirely on subjective measures. This is problematic, given the well-documented divergence between subjective perceptions and actual neurocognitive performance, including in this patient group. MATERIAL AND METHODS: Subjective and objective measures of neurocognitive performance were obtained from 25 patients with well-characterized CFS before and after the completion of a 12-week graded-activity program incorporating a cognitive training component. Additionally, self-reported symptoms, cardiac autonomic activity (a relevant biomarker of stress responsivity), and their relation to neurocognitive improvements were examined. RESULTS: Substantive post-intervention improvements in subjective (p=0.006) and objective (including faster responses speeds and greater accuracy, p's<0.001) neurocognitive performance were documented. Participants also demonstrated reduced autonomic reactivity to the cognitive challenge at follow-up (p's<=0.01). These improvements were accompanied by improvements in symptom ratings (p's<=0.01). However, subjective ratings of neurocognitive difficulties, and CFS related symptoms were not linked to objective performance improvements. CONCLUSIONS: These initial data provide the first evidence of objective neurocognitive performance improvements accompanied by a significant reduction in responsiveness in stress-related neural pathways consequent to cognitive behavioral/graded exercise therapy programs. These findings provide support for the effectiveness of such programs in remediating clinical status. These promising findings warrant further investigation, including replication in a larger sample utilizing more controlled study designs. PMID- 26995251 TI - Suicidal ideation, suicide attempt, and occupations among employed adults aged 18 64years in the United States. AB - OBJECTIVE: Approximately 70% of all US suicides are among working-age adults. This study was to determine whether and how 12-month suicidal ideation and suicide attempt were associated with specific occupations among currently employed adults aged 18-64 in the U.S. METHODS: Data were from 184,300 currently employed adults who participated in the 2008-2013 National Surveys on Drug Use and Health (NSDUH). NSDUH provides nationally representative data on suicidal ideation and suicide attempt. Descriptive analyses and multivariable logistic regressions were conducted. RESULTS: Among currently employed adults aged 18-64 in the U.S., 3.5% had suicidal ideation in the past 12months (3.1% had suicidal ideation only, and 0.4% had suicidal ideation and attempted suicide). Compared with adults in farming, fishing, and forestry occupations (model adjusted prevalence (MAP)=1.6%), adults in the following occupations were 3.0-3.6 times more likely to have suicidal ideation in the past year (model adjusted relative risks (MARRs)=3.0-3.6): lawyers, judges, and legal support workers (MAP=4.8%), social scientists and related workers (MAP=5.4%), and media and communication workers (MAP=5.8%). CONCLUSIONS: Among employed adults aged 18-64 in the U.S., the 12-month prevalence of suicidal ideation varies by occupations. Adults in occupations that are at elevated risk for suicidal ideation may warrant focused suicide prevention. PMID- 26995252 TI - Body focused repetitive behavior disorders: Significance of family history. AB - BACKGROUND: The significance of family history in body-focused repetitive behavior disorders (BFRBs) (i.e. trichotillomania and skin picking) has received scant research attention. We sought to understand the clinical and cognitive impact of having a first-degree relative with a BFRB or a substance use disorder (SUD). METHODS: 265 participants with BFRBs undertook clinical and neurocognitive evaluations. Those with a first-degree relative with a BFRB or an SUD were compared to those without on a number of clinical and cognitive measures. RESULTS: 77 (29.1%) participants had a first-degree family member with a BFRB and 59 (22.2%) had a first-degree family member with an SUD. In terms of clinical severity, the amount of time spent picking or pulling per day in the past week was higher among those with a first-degree relative with an SUD. There were a higher rate of ADHD and higher HAM-D scores among those with a positive family history of an SUD. There were no significant cognitive differences based on family history. CONCLUSIONS: These results indicate that among those with BFRBs, having a first-degree family member with an SUD may be associated with a unique clinical and cognitive presentation. Whether family history also is associated with differential response to treatments awaits further research. PMID- 26995253 TI - Perceptions of social dominance through facial emotion expressions in euthymic patients with bipolar I disorder. AB - The ability to accurately perceive dominance in the social hierarchy is important for successful social interactions. However, little is known about dominance perception of emotional stimuli in bipolar disorder. The aim of this study was to investigate the perception of social dominance in patients with bipolar I disorder in response to six facial emotional expressions. Participants included 35 euthymic patients and 45 healthy controls. Bipolar patients showed a lower perception of social dominance based on anger, disgust, fear, and neutral facial emotional expressions compared to healthy controls. A negative correlation was observed between motivation to pursue goals or residual manic symptoms and perceived dominance of negative facial emotions such as anger, disgust, and fear in bipolar patients. These results suggest that bipolar patients have an altered perception of social dominance that might result in poor interpersonal functioning. Training of appropriate dominance perception using various emotional stimuli may be helpful in improving social relationships for individuals with bipolar disorder. PMID- 26995254 TI - Assessing self-reported clinical high risk symptoms in community-derived adolescents: A psychometric evaluation of the Prodromal Questionnaire-Brief. AB - BACKGROUND: The reliable early identification of individuals at risk for psychosis requires well-validated screening measures. To date, there is little information about the psychometric properties of the screening measures for psychosis risk in nonclinical adolescents. The main purpose of the present study was to validate the Prodromal Questionnaire-Brief (PQ-B) in a community sample of non-clinical Spanish adolescents. We also analyzed the prevalence, factorial validity, and reliability of the PQ-B scores as well as the relationship between self-reported clinical high risk symptoms and schizotypal traits. METHOD: Four hundred and forty-nine high-school students participated in a cross-sectional survey. The PQ-B and the Oviedo Schizotypy Assessment Questionnaire (ESQUIZO-Q) were used. RESULTS: Although 85.1% of the total sample reported at least one clinical high risk symptom, only 16% of the adolescents scored above the standardized cut-off. The PQ-B revealed an essentially unidimensional structure. The internal consistency of the PQ-B total score was 0.93. Pearson correlation coefficients indicated a high degree of overlap between self-reported clinical high risk symptoms and Positive and Disorganized schizotypal traits. A Canonical correlation between the PQ-B total score and ESQUIZO-Q dimensions showed that the associated variance between both sets of variables was 45.4% (adjusted R(2)=0.45). CONCLUSIONS: The PQ-B is a brief, easy, and reliable tool for screening self-reported clinical high risk symptoms in adolescents from the general population. These results also indicated that self-reported clinical high risk symptoms and schizotypal traits are closely associated at the subclinical level. The assessment of psychosis risk symptoms and their relationship with other distal risk factors, in a close-in strategy, may enhance the early identification of individuals at heightened risk for psychosis spectrum disorders. PMID- 26995255 TI - Validation of the Behavioral Activation for Depression Scale (BADS)-Psychometric properties of the long and short form. AB - With the development of the Behavioral Activation for Depression Scale (BADS) by Kanter, et al. [1], different behavioral aspects of depression like activation, rumination or avoidance, and functional impairment can be measured. The long and the short versions of the BADS, however, show differences in the quality of psychometric properties. We wanted to validate the short and long forms of the BADS. We therefore evaluated the factor structure, the psychometric properties, and the construct validity of the long version and the subscales in a clinically depressed German sample (n=258) in study 1. In study 2, we explored the factor structure and the psychometric properties of the short version of the BADS in a subsyndromal sample with elevated depressive symptoms (n=406). In study 1, our results replicated the four factor solution of the BADS-25 original version and showed good psychometric properties. However, with regard to the BADS-9 only the French factor solution of the short BADS-9 demonstrated acceptable fit with low internal consistency of the subscale Avoidance. Thus, only the total score of the short form can be recommended. PMID- 26995256 TI - The effect of adaptive servo ventilation (ASV) on objective and subjective outcomes in Cheyne-Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF): A systematic review. AB - To summarize the current evidence for adaptive servo ventilation (ASV) in Cheyne Stokes respiration (CSR) with central sleep apnea (CSA) in heart failure (HF) and advance a research agenda and clinical considerations for ASV-treated CSR-CSA in HF. CSR-CSA in HF is associated with higher overall mortality, worse outcomes and lower quality of life (QOL) than HF without CSR-CSA. Five databases were searched using key words (n = 234). Randomized controlled trials assessed objective sleep quality, cardiac, and self-reported outcomes in adults (>=18 years) with HF (n = 10). ASV has a beneficial effect on the reduction of central sleep apnea in adult patients with CSR-CSA in HF, but it is not be superior to CPAP, bilevel PPV, or supplemental oxygen in terms of sleep quality defined by polysomnography, cardiovascular outcomes, subjective daytime sleepiness, and quality of life. ASV is not recommended for CSR-CSA in HF. It is important to continue to refer HF patients for sleep evaluation to clearly discern OSA from CSR-CSA. Symptom management research, inclusive of objective and subjective outcomes, in CSR-CSA in HF adults is needed. PMID- 26995257 TI - Passing the baton. PMID- 26995258 TI - Renal lymph: a window for renal pathophysiology? PMID- 26995259 TI - CO2 - friend or foe? PMID- 26995260 TI - Channelling frozen cells to survival after thawing: opening the door to cryo physiology. PMID- 26995261 TI - A 'passive' movement into the future of assessing endothelial dysfunction? PMID- 26995262 TI - The peripheral-central chemoreflex interaction: where do we stand and what is the next step? PMID- 26995263 TI - Autonomic and neuroendocrine dysfunction in chronic disease. PMID- 26995264 TI - Corrigendum. PMID- 26995265 TI - Emergency department 'undercrowding' is associated with decreased waiting times. AB - OBJECTIVE: To evaluate the effect of a sudden and sustained decrease in patient presentations on waiting times and other measures of workload and flow following the opening of a large, greenfields ED adjacent to our own. METHOD: A descriptive study involving all patients presenting to a private urban district hospital ED for two 60 day periods, immediately before and after the opening of the tertiary hospital ED. Changes in median waiting time, case-mix distribution, method of arrival, total admissions and total waiting time were compared pre-opening and post-opening. Non-normally distributed variables were analysed using Mann-Whitney U-tests. Categorical variables were compared using chi(2) analyses. RESULTS: Patient presentations decreased by 28% with a parallel decline in median waiting time of 15 min (from 26 to 11 min) (P < 0.001). Total waiting time was approximately 29 h less per day in the post-opening period. Patient urgency by triage category did not change significantly (P = 0.316), whereas the proportion of presentations by ambulance decreased 15.9% (P = 0.048) and admission rate increased from 29.1% to 32.6% (P = 0.002). CONCLUSIONS: Patient presentation numbers are strongly associated with and likely impact on median waiting time. Understanding that controlling demand can lead to significant benefits in patient processing, flow and overall patient perceived level of care and satisfaction is relevant to any discussion on ED overcrowding and the deleterious effects of access block. PMID- 26995267 TI - The mouse gut microbiome revisited: From complex diversity to model ecosystems. AB - Laboratory mice are the most commonly used animal model in translational medical research. In recent years, the impact of the gut microbiota (i.e. communities of microorganisms in the intestine) on host physiology and the onset of diseases, including metabolic and neuronal disorders, cancers, gastrointestinal infections and chronic inflammation, became a focal point of interest. There is abundant evidence that mouse phenotypes in disease models vary greatly between animal facilities or commercial providers, and that this variation is associated with differences in the microbiota. Hence, there is a clear discrepancy between the widespread use of mouse models in research and the patchwork knowledge on the mouse gut microbiome. In the present manuscript, we summarize data pertaining to the diversity and functions of the mouse gut microbiota, review existing work on gnotobiotic mouse models, and discuss challenges and opportunities for current and future research in the field. PMID- 26995268 TI - Chronic nitrate enrichment decreases severity and induces protection against an infectious disease. AB - Excessive fertilisation is one of the most pernicious forms of global change resulting in eutrophication. It has major implications for disease control and the conservation of biodiversity. Yet, the direct link between nutrient enrichment and disease remains largely unexplored. Here, we present the first experimental evidence that chronic nitrate enrichment decreases severity and induces protection against an infectious disease. Specifically, this study shows that nitrate concentrations ranging between 50 and 250mgNO3(-)/l reduce Gyrodactylus turnbulli infection intensity in two populations of Trinidadian guppies Poecilia reticulata, and that the highest nitrate concentration can even clean the parasites from the fish. This added to the fact that host nitrate pre exposure altered the fish epidermal structure and reduced parasite intensity, suggests that nitrate protected the host against the disease. Nitrate treatments also caused fish mortality. As we used ecologically-relevant nitrate concentrations, and guppies are top-consumers widely used for mosquito bio control in tropical and often nutrient-enriched waters, our results can have major ecological and social implications. In conclusion, this study advocates reducing nitrate level including the legislative threshold to protect the aquatic biota, even though this may control an ectoparasitic disease. PMID- 26995269 TI - Intra-urban biomonitoring: Source apportionment using tree barks to identify air pollution sources. AB - It is of great interest to evaluate if there is a relationship between possible sources and trace elements using biomonitoring techniques. In this study, tree bark samples of 171 trees were collected using a biomonitoring technique in the inner city of Sao Paulo. The trace elements (Al, Ba, Ca, Cl, Cu, Fe, K, Mg, Mn, Na, P, Rb, S, Sr and Zn) were determined by the energy dispersive X-ray fluorescence (EDXRF) spectrometry. The Principal Component Analysis (PCA) was applied to identify the plausible sources associated with tree bark measurements. The greatest source was vehicle-induced non-tailpipe emissions derived mainly from brakes and tires wear-out and road dust resuspension (characterized with Al, Ba, Cu, Fe, Mn and Zn), which was explained by 27.1% of the variance, followed by cement (14.8%), sea salt (11.6%) and biomass burning (10%), and fossil fuel combustion (9.8%). We also verified that the elements related to vehicular emission showed different concentrations at different sites of the same street, which might be helpful for a new street classification according to the emission source. The spatial distribution maps of element concentrations were obtained to evaluate the different levels of pollution in streets and avenues. Results indicated that biomonitoring techniques using tree bark can be applied to evaluate dispersion of air pollution and provide reliable data for the further epidemiological studies. PMID- 26995266 TI - Sepsis: in search of cure. AB - INTRODUCTION: Sepsis is a complex inflammatory disorder believed to originate from an infection by any types of microbes and/or their products. It is the leading cause of death in intensive care units (ICUs) throughout the globe. The mortality rates depend both on the severity of infection and the host's response to infection. METHODS: Literature survey on pathobiology of sepsis in general and failure of more than hundred clinical trials conducted so far in search of a possible cure for sepsis resulted in the preparation of this manuscript. FINDINGS: Sepsis lacks a suitable animal model that mimics human sepsis. However, based on the results obtained in animal models of sepsis, clinical trials conducted so far have been disappointing. Although involvement of multiple mediators and pathways in sepsis has been recognized, only few components are being targeted and this could be the major reason behind the failure of clinical trials. CONCLUSION: Inability to recognize a single critical mediator of sepsis may be the underlying cause for the poor therapeutic intervention of sepsis. Therefore, sepsis is still considered as a disease-in search of cure. PMID- 26995270 TI - Acute animal and human poisonings from cyanotoxin exposure - A review of the literature. AB - Cyanobacterial blooms are a potential health hazard due to the ability of some species to produce toxins that are harmful to other living organisms. This review provides a comprehensive summary of anecdotal and case reports on acute poisonings in animals and humans attributable to cyanotoxin exposure in fresh- and brackish-waters. Approximately two-thirds of reported poisonings have occurred in Europe and the United States. Dogs and livestock account for the majority of reported cases involving animal exposure to cyanotoxins, while recreational activities are responsible for approximately half of reported incidents involving human exposure. Due to data limitations it is difficult to estimate the total number of animals and humans affected by cyanotoxins, however, some general observations regarding frequency and numbers affected are made. The review demonstrates that cyanotoxins have, and will likely to continue to have, potentially serious consequences for public health and animal welfare worldwide. PMID- 26995271 TI - Effect of food and acid-reducing agents on the absorption of oral targeted therapies in solid tumors. AB - Oral targeted therapies represent an increasingly important group of drugs within modern oncology. With the shift from intravenously to orally administered drugs, drug absorption is a newly introduced factor in drug disposition. The process of absorption can have a large effect on inter- and intrasubject variability in drug exposure and thereby potentially treatment benefit or the severity of toxicities. The intake of oral targeted therapies with food and concomitant use of acid reducing agents (ARAs) can significantly affect drug absorption. The size and direction of the effect of food and ARAs on drug absorption varies among drugs as a result of different chemical characteristics. Therefore, an awareness and understanding of these effects for each drug is essential to optimize patient outcomes. PMID- 26995272 TI - Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease. AB - Inflammatory bowel diseases (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic ailments of the gastrointestinal tract, characterized by recurrent inflammation. Current therapeutic strategies are based on the mitigation of symptoms, including inflammatory remission and healing of mucosal manifestations. Extensive studies have suggested that continuous oxidative damage can lead to the inflammatory signaling cascade in IBD. Curcumin, a potent modulator of cell signaling, is popular for its antioxidant and anti-inflammatory activities, and has already been shown remarkable therapeutic results in IBD. Here, we review and discuss the effects of curcumin as a therapeutic agent in the chemoprevention of IBD. PMID- 26995273 TI - The effect of the angle of acuteness of additive manufactured models and the direction of printing on the dimensional fidelity: clinical implications. AB - The influence of the acuteness of the model angle and the direction of printing was investigated on different three-dimensional (3D) printers to understand the fidelity of 3D printing. A Polyjet printer and two fused deposition modeling printers were used in the present study. Computer-aided design (CAD) models were designed in the form of a triangular prism with a height of 15 mm and with varying angles of 60 degrees , 45 degrees , 30 degrees , 20 degrees , 10 degrees , and 5 degrees . From the CAD designs, additive manufacturing (AM) models were printed in three different directions by each of the three printers. To investigate the global fidelity of the 3D printers, the height and surface outlines of the AM model cross sections were measured. The fidelity of the AM models with increasingly acute angles was not accurately reproduced when 3D printed, and the surface outlines of the AM model cross sections were different in each direction of printing for each device. Printing technology and printing direction need to be considered if accurate reproduction of acute angles in fine AM structures in medical models is a necessity. PMID- 26995275 TI - Dental implants: A review. AB - A high number of patients have one or more missing tooth and it is estimated that one in four American subjects over the age of 74 have lost all their natural teeth. Many options exist to replace missing teeth but dental implants have become one of the most used biomaterial to replace one (or more) missing tooth over the last decades. Contemporary dental implants made with titanium have been proven safe and effective in large series of patients. This review considers the main historical facts concerned with dental implants and present the different critical factors that will ensure a good osseo-integration that will ensure a stable prosthesis anchorage. PMID- 26995276 TI - Volume matters in the systemic treatment of metastatic pancreatic cancer: a population-based study in the Netherlands. AB - PURPOSE: In pancreatic surgery, a relation between surgical volume and postoperative mortality and overall survival (OS) has been recognized, with high volume centers reporting significantly better survival rates. We aimed to explore the influence of hospital volume on administration of palliative chemotherapy and OS in the Netherlands. METHODS: Patients diagnosed between 2007 and 2011 with metastatic pancreatic cancer were identified in the Netherlands Cancer Registry. Three types of high-volume centers were defined: high-volume (1) incidence center, based on the number of patients diagnosed with metastatic pancreatic cancer, (2) treatment center based on number of patients with metastatic pancreatic cancer who started treatment with palliative chemotherapy and (3) surgical center based on the number of resections with curative intent for pancreatic cancer. Independent predictors of administration of palliative chemotherapy were evaluated by means of logistic regression analysis. The multivariable Cox proportional hazard model was used to assess the impact of being diagnosed or treated in high-volume centers on survival. RESULTS: A total of 5385 patients presented with metastatic pancreatic cancer of which 24 % received palliative chemotherapy. Being treated with chemotherapy in a high volume chemotherapy treatment center was associated with improved survival (HR 0.76, 95 % CI 0.67-0.87). Also, in all patients with metastatic pancreatic cancer, being diagnosed in a high-volume surgical center was associated with improved survival (HR 0.74, 95 % CI 0.66-0.83). CONCLUSIONS: Hospital volume of palliative chemotherapy for metastatic pancreatic cancer was associated with improved survival, demonstrating that a volume-outcome relationship, as described for pancreatic surgery, may also exist for pancreatic medical oncology. PMID- 26995277 TI - Complexity analysis of brain activity in attention-deficit/hyperactivity disorder: A multiscale entropy analysis. AB - The multiscale entropy (MSE) is a novel method for quantifying the intrinsic dynamical complexity of physiological systems over several scales. To evaluate this method as a promising way to explore the neural mechanisms in ADHD, we calculated the MSE in EEG activity during the designed task. EEG data were collected from 13 outpatient boys with a confirmed diagnosis of ADHD and 13 age- and gender-matched normal control children during their doing multi-source interference task (MSIT). We estimated the MSE by calculating the sample entropy values of delta, theta, alpha and beta frequency bands over twenty time scales using coarse-grained procedure. The results showed increased complexity of EEG data in delta and theta frequency bands and decreased complexity in alpha frequency bands in ADHD children. The findings of this study revealed aberrant neural connectivity of kids with ADHD during interference task. The results showed that MSE method may be a new index to identify and understand the neural mechanism of ADHD. PMID- 26995278 TI - The effects and risks associated to mephedrone and methylone in humans: A review of the preliminary evidences. AB - New psychoactive substances have drastically modified the world drug scene. An increasingly popular class comprises synthetic or substituted cathinones (legal highs, research chemicals, bath salts). Among the most common psychoactive constituents of bath salts are mephedrone and methylone. Recent reports on the abuse of novel synthetic cathinone derivatives call attention to the serious physical and psychological risks resulting from their consumption, thereby emphasizing the growing use of these drugs might constitute an important public health issue. In this paper, we will review the available data regarding the use and effects of mephedrone and methylone in humans in order to highlight their impact on public health. To reach this objective, a literature search was performed on two representative databases (Pubmed, Google Scholar), the Erowid Center website (a US non-profit educational organization that provides information about psychoactive plants and chemicals), and various governmental websites. The terms used for the database search were "mephedrone", "methylone", "new psychoactive substances", "synthetic cathinones", "substituted cathinones", "substance abuse", "substance use disorder", "adverse effects", "fatalities". The literature search was limited to years 2005-2015 and led to the identification of 71 potentially relevant articles. To date, the actual prevalence rates of their use remains difficult to estimate. Important health-related issues have emerged in relation to the somatic, psychiatric, and addictive consequences of their use. The potential chronic health effects of their prolonged use remain to date unknown (e.g., reproductive toxicity, genotoxicity and carcinogenic potential). Treatment for patients with prolonged exposure to synthetic cathinones should ideally include a drug management plan coupled with psychotherapy taking place in a structured program of care. PMID- 26995279 TI - The antiproliferative and proapoptotic effects of cladosporols A and B are related to their different binding mode as PPARgamma ligands. AB - Cladosporols are secondary metabolites from Cladosporium tenuissimum characterized for their ability to control cell proliferation. We previously showed that cladosporol A inhibits proliferation of human colon cancer cells through a PPARgamma-mediated modulation of gene expression. In this work, we investigated cladosporol B, an oxidate form of cladosporol A, and demonstrate that it is more efficient in inhibiting HT-29 cell proliferation due to a robust G0/G1-phase arrest and p21(waf1/cip1) overexpression. Cladosporol B acts as a PPARgamma partial agonist with lower affinity and reduced transactivation potential in transient transfections as compared to the full agonists cladosporol A and rosiglitazone. Site-specific PPARgamma mutants and surface plasmon resonance (SPR) experiments confirm these conclusions. Cladosporol B in addition displays a sustained proapoptotic activity also validated by p21(waf1/cip1) expression analysis in the presence of the selective PPARgamma inhibitor GW9662. In the DMSO/H2O system, cladosporols A and B are unstable and convert to the ring opened compounds 2A and 2B. Finally, docking experiments provide the structural basis for full and partial PPARgamma agonism of 2A and 2B, respectively. In summary, we report here, for the first time, the structural characteristics of the binding of cladosporols, two natural molecules, to PPARgamma. The binding of compound 2B is endowed with a lower transactivation potential, higher antiproliferative and proapoptotic activity than the two full agonists as compound 2A and rosiglitazone (RGZ). PMID- 26995281 TI - Track: A randomized controlled trial of a digital health obesity treatment intervention for medically vulnerable primary care patients. AB - INTRODUCTION: Obesity continues to disproportionately affect medically vulnerable populations. Digital health interventions may be effective for delivering obesity treatment in low-resource primary care settings. METHODS: Track is a 12-month randomized controlled trial of a digital health weight loss intervention in a community health center system. Participants are 351 obese men and women aged 21 to 65years with an obesity-related comorbidity. Track participants are randomized to usual primary care or to a 12-month intervention consisting of algorithm generated tailored behavior change goals, self-monitoring via mobile technologies, daily self-weighing using a network-connected scale, skills training materials, 18 counseling phone calls with a Track coach, and primary care provider counseling. Participants are followed over 12months, with study visits at baseline, 6, and 12months. Anthropometric data, blood pressure, fasting lipids, glucose and HbA1C and self-administered surveys are collected. Follow-up data will be collected from the medical record at 24months. RESULTS: Participants are 68% female and on average 50.7years old with a mean BMI of 35.9kg/m(2). Participants are mainly black (54%) or white (33%); 12.5% are Hispanic. Participants are mostly employed and low-income. Over 20% of the sample has hypertension, diabetes and hyperlipidemia. Almost 27% of participants currently smoke and almost 20% score above the clinical threshold for depression. CONCLUSIONS: Track utilizes an innovative, digital health approach to reduce obesity and chronic disease risk among medically vulnerable adults in the primary care setting. Baseline characteristics reflect a socioeconomically disadvantaged, high-risk patient population in need of evidence-based obesity treatment. PMID- 26995280 TI - Evaluation of a culturally-adapted lifestyle intervention to treat elevated cardiometabolic risk of Latino adults in primary care (Vida Sana): A randomized controlled trial. AB - Latinos bear a disproportionate burden of the dual pandemic of obesity and diabetes. However, successful interventions addressing this disparity through primary care are lacking. To address this gap, the 5-year Vida Sana (Healthy Life) study tests a culturally adapted and technology-enhanced group-based Diabetes Prevention Program intervention in a randomized controlled trial with overweight/obese Latino adults who have metabolic syndrome and/or pre-diabetes. Eligible, consenting patients (n=186) from a large community-based multispecialty group practice in Northern California will be randomly assigned to receive the culturally-adapted intervention or usual care. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework guided the planned evaluations. The primary aim is to determine the effectiveness of the intervention (the "E" in RE-AIM). We hypothesize that the intervention will lead to a greater mean reduction in weight at 24months (primary endpoint) vs. usual care. Secondary outcomes will include measures of cardiometabolic risk factors (e.g., blood pressure), psychosocial well-being (e.g., health-related quality of life), and behavior change (e.g., physical activity). The secondary aim is to evaluate the other RE-AIM dimensions using mixed methods: reach (e.g., participation rate of the target population), adoption (e.g., participating clinic and provider characteristics), implementation (e.g., intervention fidelity), and maintenance (e.g., sustainability in the practice setting). These findings have real word applicability with value to clinicians, patients, and other decision makers considering effective diabetes prevention programs for primary care that would support the millions of Latino adults who experience a disproportionate burden of diabetes. TRIAL REGISTRATION: NCT02459691. PMID- 26995283 TI - Is ultrasound-guided fine-needle aspiration cytology of adequate value in detecting breast cancer patients with three or more positive axillary lymph nodes? AB - This study evaluated the accuracy of ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC) to select early breast cancer patients with three or more tumour-positive axillary lymph nodes. Between 2004 and 2014, a total of 2130 patients with histologically proven early breast cancer were evaluated and treated in the Noordwest Clinics Alkmaar. US/FNAC was performed preoperatively in all these patients. We analysed the results of US/FNAC retrospectively. Pathological axillary node status (sentinel node biopsy and/or axillary lymph node dissection) was used as reference standard. A total of 634 (29.8 %) of 2130 patients had axillary lymph node metastases on final histology. 248 node positive patients (11.6 %) had three or more positive lymph nodes. The accuracy of US/FNAC to detect three or more positive lymph nodes was 89.8 %, sensitivity was 44.8 %, specificity was 95.7 %, PPV was 58.1 %, and NPV was 92.9 %. This study shows a more than adequate accuracy of preoperative US/FNAC to detect three or more positive lymph nodes (89.8 %). However, when US/FNAC was chosen as the only axillary staging method, 6.4 % of all patients (false negative group) would have been undertreated and 3.8 % of all patients (false positive group) would have been overtreated according to the ACOSOG Z0011 criteria. PMID- 26995282 TI - Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells. AB - Traf2- and Nck-interacting kinase (TNIK) is a member of the germinal center kinase family. TNIK was first identified as a kinase that is involved in regulating cytoskeletal organization in many types of cells, and it was recently proposed as a novel therapeutic target in several types of human cancers. Although previous studies suggest that TNIK plays a pivotal role in cancer cell survival and prognosis, its function in hematological cancer cell survival has not been investigated. Here we investigated the relationship between TNIK function and cell viability in multiple myeloma IM-9 cells using TNIK small interfering RNA (siRNA) transfection and dovitinib treatment. Treatment of IM-9 cells with TNIK siRNA and dovitinib treatment reduced cell proliferation. The ATP competing kinase assay and western blot analysis showed that dovitinib strongly inhibited both the interaction of TNIK with ATP (K i, 13 nM) and the activation of Wnt signaling effectors such as beta-catenin and TCF4. Dovitinib also induced caspase-dependent apoptosis in IM-9 cells without significant cytotoxicity in PBMCs. Our results provide new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway. PMID- 26995284 TI - Label-free DNA biosensor based on resistance change of platinum nanoparticles assemblies. AB - A novel nanoparticle based biosensor for the fast and simple detection of DNA hybridization events is presented. The sensor utilizes hybridized DNA's charge transport properties, combining them with metallic nanoparticle networks that act as nano-gapped electrodes. The DNA hybridization events can be detected by a significant reduction in the sensor's resistance due to the conductive bridging offered by hybridized DNA. By modifying the nanoparticle surface coverage, which can be controlled experimentally being a function of deposition time, and the structural properties of the electrodes, an optimized biosensor for the in situ detection of DNA hybridization events is ultimately fabricated. The fabricated biosensor exhibits a wide response range, covering four orders of magnitude, a limit of detection of 1nM and can detect a single base pair mismatch between probe and complementary DNA. PMID- 26995285 TI - Monitoring gamma-glutamyl transpeptidase activity and evaluating its inhibitors by a water-soluble near-infrared fluorescent probe. AB - The first near-infrared fluorescent probe with excellent water-solubility for gamma-glutamyl transpeptidase (GGT) has been developed by combining glutathione (GSH) as a recognition unit with a near-infrared hemicyanine fluorophore through an acrylyl linker. The probe exhibits a highly selective and sensitive fluorescent off-on response to GGT with a detection limit of 0.50U/L, and the response mechanism is based on the enzyme-catalyzed cleavage of the gamma glutamyl bond of GSH, followed by the spontaneous intramolecular cyclization and the release of the fluorophore. Notably, the probe has been used to image GGT in zebrafish and evaluate the inhibition ability of three common inhibitors of GGT both in vitro and in vivo, revealing that their inhibition efficiencies are acivicin >6-diazo-5-oxo-L-norleucine >L-serine-borate complex, and their corresponding IC50 values are 0.11+/-0.01mM, 0.34+/-0.04mM and 2.06+/-0.24mM, respectively. The proposed probe is simple, and may have great potential for screening GGT inhibitors. PMID- 26995286 TI - Real-time monitoring of macromolecular biosensing probe self-assembly and on-chip ELISA using impedimetric microsensors. AB - This paper presents a comprehensive study of the self-assembly dynamics and the biosensing efficacy of Tobacco mosaic virus-like particle (TMV VLP) sensing probes using an impedimetric microsensor platform. TMV VLPs are high surface area macromolecules with nanorod structures constructed from helical arrangements of thousands of identical coat proteins. Genetically modified TMV VLPs express both surface attachment-promoting cysteine residues and FLAG-tag antibody binding peptides on their coat protein outer surfaces, making them selective biosensing probes with self-assembly capability on sensors. The VLP self-assembly dynamics were studied by the continuous monitoring of impedance changes at 100Hz using interdigitated impedimetric microsensors. Electrical impedance spectroscopy revealed VLP saturation on impedance sensor surface with the coverage of 68% in self-assembly process. The VLP-functionalized impedance sensors responded to 12ng/ml to 1.2MUg/ml of target anti-FLAG IgG antibodies in the subsequent enzyme linked immunosorbent assays (ELISA), and yielded 18-35% total impedance increases, respectively. The detection limit of the target antibody is 9.1ng/ml using the VLP-based impedimetric microsensor. These results highlight the significant potential of genetically modified VLPs as selective nanostructured probes for autonomous sensor functionalization and enhanced biosensing. PMID- 26995287 TI - Single cell multiplexed assay for proteolytic activity using droplet microfluidics. AB - Cellular enzymes interact in a post-translationally regulated fashion to govern individual cell behaviors, yet current platform technologies are limited in their ability to measure multiple enzyme activities simultaneously in single cells. Here, we developed multi-color Forster resonance energy transfer (FRET)-based enzymatic substrates and use them in a microfluidics platform to simultaneously measure multiple specific protease activities from water-in-oil droplets that contain single cells. By integrating the microfluidic platform with a computational analytical method, Proteolytic Activity Matrix Analysis (PrAMA), we are able to infer six different protease activity signals from individual cells in a high throughput manner (~100 cells/experimental run). We characterized protease activity profiles at single cell resolution for several cancer cell lines including breast cancer cell line MDA-MB-231, lung cancer cell line PC-9, and leukemia cell line K-562 using both live-cell and in-situ cell lysis assay formats, with special focus on metalloproteinases important in metastasis. The ability to measure multiple proteases secreted from or expressed in individual cells allows us to characterize cell heterogeneity and has potential applications including systems biology, pharmacology, cancer diagnosis and stem cell biology. PMID- 26995288 TI - The use of zygomatic implants for the retention of nasal prosthesis following rhinectomy: the Morriston experience. AB - Reconstruction and rehabilitation following rhinectomy remains controversial and presents a complex problem. Although reconstruction with local and microvascular flaps is a valid option, the aesthetic results may not always be satisfactory. The aesthetic results achieved with a nasal prosthesis are excellent; however patient acceptance relies on a secure method of retention. The technique used and results obtained in a large series of patients undergoing rhinectomy and receiving zygomatic implants for the retention of a nasal prosthesis are described here. A total of 56 zygomatic implants (28 patients) were placed, providing excellent retention and durability with the loss of only one implant in 15 years. PMID- 26995289 TI - Abdominal tuberculosis in a low prevalence country. AB - OBJECTIVE: Abdominal tuberculosis is a rare disease. The clinical and radiological manifestations are non-specific and the diagnosis is difficult. Our objective was to describe the characteristics and treatment of patients presenting with abdominal tuberculosis in a low-incidence country. PATIENTS AND METHODS: We reviewed the clinical, diagnostic, treatment, and outcome features of patients presenting with abdominal tuberculosis diagnosed by bacteriological and/or histological results and managed in five French university hospitals from January 2000 to December 2009. RESULTS: We included 21 patients. The mean diagnostic delay was 13 months. Twelve patients (57%) came from a low-incidence area and only two had a known immunosuppressed condition. Eighteen patients (86%) presented with abdominal symptoms. The main organs involved were the peritoneum (n=14, 66%), the mesenteric lymph nodes (n=13, 62%), and the bowel (n=7, 33%). Sixteen patients (76%) underwent surgery, including two in an emergency setting. Seventeen patients (81%) received six months or more of anti-tuberculosis treatment. Finally, 16 patients (76%) had a positive outcome. CONCLUSION: New diagnostic procedures, and especially molecular biology, may help diagnose unusual clinical presentations of tuberculosis. Invasive procedures are frequently necessary to obtain samples but also for the treatment of digestive involvement. PMID- 26995290 TI - Significance of synaptic Zn2+ signaling in zincergic and non-zincergic synapses in the hippocampus in cognition. AB - A portion of zinc concentrates in the synaptic vesicles in the brain and is released from glutamatergic (zincergic) neuron terminals. It serves as a signaling factor (in a form of free Zn2+). Both extracellular Zn2+ signaling, which predominantly originates in Zn2+ release from zincergic neuron terminals, and intracellular Zn2+ signaling, which is often linked to extracellular Zn2+ signaling, are involved in hippocampus-dependent memory. At mossy fiber-CA3 pyramidal cell synapses and Schaffer collateral-CA1 pyramidal cell synapses, which are zincergic, extracellular Zn2+ signaling leads to intracellular Zn2+ signaling and is involved in learning and memory. At medial perforant pathway dentate granule cell synapses, which are non-zincergic, intracellular Zn2+ signaling, which originates in the internal stores containing Zn2+, is involved in learning and memory. The blockade of Zn2+ signaling with Zn2+ chelators induces memory deficit, while the optimal amount range of Zn2+ signaling is unknown. It is possible that the degree and frequency of Zn2+ signaling, which determine the increased Zn2+ levels, modulates learning and memory as well as intracellular Ca2+ signaling. To understand the precise role of synaptic Zn2+ signaling in the hippocampus, the present paper summarizes the current knowledge on Zn2+ signaling at zincergic and non-zincergic synapses in the hippocampus in cognition and involvement of zinc transporters and zinc-binding proteins in synaptic Zn2+ signaling. PMID- 26995291 TI - Evaluating College Students' Displayed Alcohol References on Facebook and Twitter. AB - PURPOSE: Current trends suggest that adolescents and young adults typically maintain a social media "portfolio" of several sites including Facebook and Twitter, but little is known regarding how an individual chooses to display risk behaviors across these different sites. The purpose of this study was to investigate college students' displayed alcohol references on both Facebook and Twitter. METHODS: Among a larger sample of college students from two universities, we identified participants who maintained both Facebook and Twitter profiles. Data collection included evaluation of 5 months of participants' Facebook and Twitter posts for alcohol references, number of social connections (i.e., friends or followers), and number of posts. Phone interviews assessed participants' frequency of Facebook and Twitter use and self-reported alcohol use. Analyses included Fisher's exact test, Wilcoxon matched pair sign test, Friedman rank-sum tests, and logistic regression. RESULTS: Of 112 eligible participants, 94 completed the study. Participants were more likely to display alcohol references on Facebook compared with those on Twitter (76% vs. 34%, p = .02). Participants reported more social connections on Facebook versus Twitter (average 801.2 friends vs. 189.4 followers, p < .001) and were more likely to report daily use of Facebook versus Twitter (94.6% vs. 50%, p < .001). Current alcohol use was predictive of both Facebook and Twitter displayed alcohol references, but mediators differed in each model. CONCLUSIONS: College students were more likely to display alcohol references on Facebook compared with those on Twitter. Understanding these patterns and predictors may inform prevention and intervention efforts directed at particular social media sites. PMID- 26995292 TI - Temporal Effects of Child and Adolescent Exposure to Neighborhood Disadvantage on Black/White Disparities in Young Adult Obesity. AB - PURPOSE: This study investigates the effects of duration and timing of exposure to neighborhood disadvantage from birth through age 17 years on obesity incidence in early adulthood and black/white disparities therein. METHODS: Individual- and household-level data from the 1970-2011 waves of the Panel Study of Income Dynamics are merged with census data on respondents' neighborhoods (n = 1,498). Marginal structural models with inverse probability of treatment and censoring weights are used to quantify the probability of being obese at least once between ages 18 and 30 years as a function of cumulative exposure to neighborhood disadvantage throughout childhood and adolescence or during each of three developmental stages therein. RESULTS: Longer term exposure to neighborhood disadvantage from ages 0-17 years is more common among blacks than among whites and is associated with significantly greater odds of being obese at least once in early adulthood. Exposure to neighborhood-level deprivation during adolescence (ages 10-17 years) appears more consequential for future (young adult) obesity than exposure that occurs earlier in childhood. CONCLUSIONS: The duration and timing of exposure to neighborhood disadvantage during childhood and adolescence are associated with obesity incidence in early adulthood for both blacks and whites. However, given inequalities in the likelihood and persistence of experiencing neighborhood disadvantage as children and youth, such adverse effects are likely to be more concentrated among black versus white young adults. PMID- 26995293 TI - Prevalence of hypercalcemia related to hypervitaminosis D in clinical practice. AB - BACKGROUND & AIMS: Recent interest in vitamin D has led to a substantial increase in the use of vitamin D supplements. Vitamin D intoxication may be a concern as hypervitaminosis D can result in irreversible calcification of soft tissues so that it is important to detect early markers of vitamin D intoxication. Our aim was to assess the simultaneous presence of biochemical markers of vitamin D toxicity (i.e. hypervitaminosis D, hypercalcemia) and determine the concentrations of 25-OH-vitamin D at which the risk of hypercalcemia, and thus toxicity, might begin. METHODS: We evaluated retrospectively a 6-year period during which 25.567 samples were assessed for 25-OH-vitamin D status by UHPLC. Hypervitaminosis D was defined at serum 25-OH-vitamin D >160 nmol/L. Serum and urine calcium, phosphorus and iPTH were also recorded, if available. Medical history revision was performed in subjects displaying simultaneously hypervitaminosis D and hypercalcemia. RESULTS: Overall, hypervitaminosis D was found in 475 samples (1.86%) of which 51 displayed hypercalcemia (11.1%). A total of 382 samples were identified as the first record of hypervitaminosis D and 39 presented hypercalcemia (10.2%), most of them at 25-OH-vitamin D levels between 161 and 375 nmol/L. Only in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l. In no case, serum calcium achieved concentrations considered as critical values (>13 mg/dl). CONCLUSION: Hypercalcemia due to vitamin D represented <4% of the total hypervitaminosis D detected and <0.1% of the tests performed. However, a highly variable response was observed and most subjects presented hypercalcemia at serum concentrations of 25-OH-vitamin D < 375 nmol/L. PMID- 26995294 TI - Expanding the Range of CRISPR/Cas9 Genome Editing in Rice. PMID- 26995295 TI - Promoting Artemisinin Biosynthesis in Artemisia annua Plants by Substrate Channeling. PMID- 26995296 TI - An INDEHISCENT-Controlled Auxin Response Specifies the Separation Layer in Early Arabidopsis Fruit. AB - Seed dispersal is an important moment in the life cycle of a plant species. In Arabidopsis thaliana, it is dependent on transcription factor INDEHISCENT (IND) mediated specification of a separation layer in the dehiscence zone found in the margin between the valves (carpel walls) and the central replum of the developing fruit. It was proposed that IND specifies the separation layer by inducing a local auxin minimum at late stages of fruit development. Here we show that morphological differences between the ind mutant and wild-type fruit already arise at early stages of fruit development, coinciding with strong IND expression in the valve margin. We show that IND-reduced PIN-FORMED3 (PIN3) auxin efflux carrier abundance leads to an increased auxin response in the valve margin during early fruit development, and that the concomitant cell divisions that form the dehiscence zone are lacking in ind mutant fruit. Moreover, IND promoter-driven ectopic expression of the AGC kinases PINOID (PID) and WAG2 induced indehiscence by expelling auxin from the valve margin at stages 14-16 of fruit development through increased PIN3 abundance. Our results show that IND, besides its role at late stages of Arabidopsis fruit development, functions at early stages to facilitate the auxin-triggered cell divisions that form the dehiscence zone. PMID- 26995297 TI - Complicated Genitourinary Tract Infections and Mimics. AB - This article provides pictorial review of complicated upper and lower genitourinary infections and their mimics. Imaging features of upper urinary tract infections including uncomplicated acute pyelonephritis, xanthogranulomatous pyelonephritis (XGPN), emphysematous pyelonephritis, perirenal abscess, and pyonephrosis are first reviewed and then followed by pictorial review of their mimics including contrast-associated nephrotoxicity, renal infarcts, malakoplakia, renal cell cancer, leukemia or lymphoma and Castleman's disease. Next, imaging features of lower urinary tract infections including cystitis, emphysematous cystitis, enterovesical, colovesical and vesicovaginal fistulas, Fournier gangrene, prostatitis, epididymitis, and orchitis are reviewed and then followed by pictorial review of their mimics including gas in the bladder and perineum related to instrumentation, radiation cystitis, bladder cancer, testicular torsion, testicular trauma, and testicular cancer and lymphoma. Recognizing imaging characteristics of complicated genitourinary infections and their mimics would allow clinicians to provide appropriate timely management. PMID- 26995299 TI - Treating cognitive impairment in depression: an unmet need. PMID- 26995298 TI - Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study. AB - BACKGROUND: Antidepressant treatment failure is a common problem worldwide. In this study, we assess whether or not an important aspect of depression, cognitive impairment, is untreated by antidepressants by studying the effect of acute antidepressant treatment on a range of cognitive domains. METHODS: In this randomised longitudinal study, which is part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial, we assessed the effects of acute antidepressant treatment in a large patient population, across clinical remission outcomes, on a range of cognitive domains: attention, response inhibition, executive function during visuospatial navigation, cognitive flexibility, verbal memory, working memory, decision speed, information processing speed, and psychomotor response speed. We enrolled patients from primary or specialty care clinics in a multicentre, international, open-label, randomised, prospective trial. Eligible patients (aged 18-65 years) were previously untreated or were willing to undergo a 1-week medication washout before the study start, and could not have had inadequate response to study medications in the past. We enrolled a large population of medication-free (ie, untreated) outpatients in a depressive episode and assessed them for cognitive function at enrolment (pre-treatment), and again after 8 weeks of treatment with one of three antidepressant drugs (escitalopram, sertraline, or venlafaxine extended-release). Patients were randomly assigned (1:1:1) to one of the three antidepressants using a blocked randomisation procedure (block size of 12). As a comparison group, we also simultaneously enrolled matched healthy participants. Healthy participants received no medication or intervention, but were assessed for change in cognitive and clinical measures during the same interval and testing protocol. Therefore, this group acts as a test-retest control for the primary outcome measure examined in this study, change in cognitive measures over 8 weeks of treatment in depressed patients. This study is registered with ClinicalTrials.gov, number NCT00693849. FINDINGS: Between Dec 8, 2008, and Sept 30, 2011, we enrolled 1008 eligible people into the study. Impairment in five domains-attention, response inhibition, verbal memory, decision speed, and information processing-showed no relative improvement with acute treatment (controlling for time or repeated testing), irrespective of antidepressant treatment group, even in patients whose depression remitted acutely according to clinical measures. Broader cognitive impairment was associated with greater illness chronicity (earlier illness onset) but not with symptom severity or previous antidepressant failures. INTERPRETATION: Depression is associated with impairments in higher-order cognitive functions and information processing, which persist independently of clinical symptom change with treatment. We recorded no difference between the three antidepressants tested, with none showing efficacy for these impairments. Although the 8-week treatment period limits interpretation to acute treatment effects, it does highlight cognitive impairment as an untargeted contributor to incomplete treatment success. FUNDING: Brain Resource Company Operations Pty Ltd and NIH. PMID- 26995300 TI - ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis. AB - The Renin Angiotensin System (RAS) is a pivotal physiological regulator of heart and kidney homeostasis, but also plays an important role in the pathophysiology of heart and kidney diseases. Recently, new components of the RAS have been discovered, including angiotensin converting enzyme 2 (ACE2), Angiotensin(Ang)-(1 7), Mas receptor, Ang-(1-9) and Alamandine. These new components of RAS are formed by the hydrolysis of Ang I and Ang II and, in general, counteract the effects of Ang II. In experimental models of heart and renal diseases, Ang-(1-7), Ang-(1-9) and Alamandine produced vasodilation, inhibition of cell growth, anti thrombotic, anti-inflammatory and anti-fibrotic effects. Recent pharmacological strategies have been proposed to potentiate the effects or to enhance the formation of Ang-(1-7) and Ang-(1-9), including ACE2 activators, Ang-(1-7) in hydroxypropyl beta-cyclodextrin, cyclized form of Ang-(1-7) and nonpeptide synthetic Mas receptor agonists. Here, we review the role and effects of ACE2, ACE2 activators, Ang-(1-7) and synthetic Mas receptor agonists in the control of inflammation and fibrosis in cardiovascular and renal diseases and as counter regulators of the ACE-Ang II-AT1 axis. We briefly comment on the therapeutic potential of the novel members of RAS, Ang-(1-9) and alamandine, and the interactions between classical RAS inhibitors and new players in heart and kidney diseases. PMID- 26995301 TI - Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: A systematic review and meta-analysis. AB - Chronic kidney disease (CKD) represents an important health problem worldwide and the search for new therapeutic approaches for retarding CKD progression is a timely issue. Recent evidence suggest that the anti-inflammatory and hemorrheologic drug Pentoxifylline (PTX), may produce favorable effects on kidney function. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to ascertain whether PTX derivatives, alone or in combination to other treatments, may be useful in slowing down disease progression in patients with diabetic or non-diabetic CKD. We found 26 studies (1518 subjects) matching our search criteria. Information on the effects of PTX on hard renal outcomes (doubling of serum creatinine or need for chronic dialysis) were lacking in all the reviewed trials. Conversely, PTX was effective in reducing proteinuria compared to control, a benefit that was more evident in patients with type-1 diabetes mellitus, higher proteinuria at baseline and early renal impairment. An improvement in renal function (eGFR/creatinine clearance) was observed particularly in patients with more advanced CKD stage and in studies with longer follow-up. Conversely, cumulative analyses did not reveal any evident reduction in urinary albumin excretion, even in diabetic patients. The use of PTX was relatively safe as most trials recorded only minor gastrointestinal adverse effects. Although these findings point at some reno-protective effects of PTX, there is no conclusive evidence proving the usefulness of this agent for improving renal outcomes in subjects with chronic kidney disease of various etiology. Future trials adequately powered and designed on hard clinical end points are needed. PMID- 26995302 TI - RAAS inhibition and the course of Alport syndrome. AB - Alport syndrome (AS) is a hereditary progressive glomerulonephritis with a high life-time risk for end-stage renal disease (ESRD). Most patients will reach ESRD before the age of 30 years, while a subset of them with milder mutations will do so at older ages, even after 50 years. Frequent extrarenal manifestations are hearing loss and ocular abnormalities. AS is a genetically heterogeneous collagen IV nephropathy, with 85% of the cases caused by mutations in the X-linked COL4A5 gene and the rest by homozygous or compound heterozygous mutations in either the COL4A3 or the COL4A4 gene on chromosome 2q36-37. There is no radical cure for the disease and attempts to use various stem cell therapies in animal models have been met with ambiguous success. However, effective treatment has been accomplished with pharmacological intervention at the renin-angiotensin aldosterone system (RAAS), first in animal models of AS and more recently in humans. Angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) have been shown to significantly delay the progression of chronic kidney disease and the onset of ESRD. Also, renin inhibitors and aldosterone blockade were used with positive results, while the combination of ACEis and ARBs was met with mixed success. An important study, the EARLY-PROTECT, aims at evaluating the efficacy of ACEis when administered very early on in children with AS. Novel therapies are also tested experimentally or are under design in animal models by several groups, including the use of amniotic fluid stem cells and synthetic chaperones. PMID- 26995303 TI - Equol increases cerebral blood flow in rats via activation of large-conductance Ca(2+)-activated K(+) channels in vascular smooth muscle cells. AB - The present study was designed to investigate the effect of equol on cerebral blood flow and the underlying molecular mechanisms. The regional cerebral blood flow in parietal lobe of rats was measured by using a laser Doppler flowmetry. Isolated cerebral basilar artery and mesenteric artery rings from rats were used for vascular reactivity measurement with a multi wire myography system. Outward K(+) current in smooth muscle cells of cerebral basilar artery, large-conductance Ca(2+)-activated K(+) (BK) channel current in BK-HEK 293 cells stably expressing both human alpha (hSlo)- and beta1-subunits, and hSlo channel current in hSlo-HEK 293 cells expressing only the alpha-subunit of BK channels were recorded with whole cell patch-clamp technique. The results showed that equol significantly increased regional cerebral blood flow in rats, and produced a concentration dependent but endothelium-independent relaxation in rat cerebral basilar arteries. Both paxilline and iberiotoxin, two selective BK channel blockers, significantly inhibited equol-induced vasodilation in cerebral arteries. Outward K(+) currents in smooth muscle cells of cerebral basilar artery were increased by equol and fully reversed by washout or blockade of BK channels with iberiotoxin. Equol remarkably enhanced human BK current in BK-HEK 293 cells, but not hSlo current in hSlo-HEK 293 cells, and the increase was completely abolished by co application of paxilline. Our findings provide the first information that equol selectively stimulates BK channel current by acting on its beta1 subunit, which may in turn contribute to the equol-mediated vasodilation and cerebral blood flow increase. PMID- 26995305 TI - Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. AB - Cyclins and cyclin-dependent protein kinases (CDKs) are important regulatory components that are required for cell cycle progression. The levels of the cell cycle CDKs are generally constant and their activities are controlled by cyclins, proteins whose levels oscillate during each cell cycle. Additional CDK family members were subsequently discovered that play significant roles in a wide range of activities including the control of gene transcription, metabolism, and neuronal function. In response to mitogenic stimuli, cells in the G1 phase of the cell cycle produce cyclins of the D type that activate CDK4/6. These activated enzymes catalyze the monophosphorylation of the retinoblastoma protein. Then CDK2 cyclin E catalyzes the hyperphosphorylation of Rb that promotes the release and activation of the E2F transcription factors, which in turn lead to the generation of several proteins required for cell cycle progression. As a result, cells pass through the G1-restriction point and are committed to complete cell division. CDK2-cyclin A, CDK1-cyclin A, and CDK1-cyclin B are required for S, G2, and M phase progression. Increased cyclin or CDK expression or decreased levels of endogenous CDK inhibitors such as INK4 or CIP/KIP have been observed in various cancers. In contrast to the mutational activation of EGFR, Kit, or B-Raf in the pathogenesis of malignancies, mutations in the CDKs that cause cancers are rare. Owing to their role in cell proliferation, CDKs represent natural targets for anticancer therapies. Abemaciclib (LY2835219), ribociclib (Lee011), and palbociclib (Ibrance((r)) or PD0332991) target CDK4/6 with IC50 values in the low nanomolar range. Palbociclib and other CDK inhibitors bind in the cleft between the small and large lobes of the CDKs and inhibit the binding of ATP. Like ATP, palbociclib forms hydrogen bonds with residues in the hinge segment of the cleft. Like the adenine base of ATP, palbociclib interacts with catalytic spine residues CS6 and CS7. CDK antagonists are in clinical trials for the treatment of a variety of malignancies. Significantly, palbociclib has been approved by the FDA for the treatment of hormone-receptor positive/human epidermal growth factor receptor-2 negative breast cancer in conjunction with letrozole as a first-line therapy and with fulvestrant as a second-line treatment. As inhibitors of the cell cycle, it is not surprising that one of their most common toxicities is myelosuppression with decreased neutrophil production. PMID- 26995304 TI - SRPK1 inhibition in prostate cancer: A novel anti-angiogenic treatment through modulation of VEGF alternative splicing. AB - Prostate cancer remains one of the leading causes of cancer death in men around the world, regardless of intense research and development of novel therapies in the last 10 years. One of the new avenues that has been tested - inhibition of angiogenesis - has been disappointing so far in clinical studies in spite of strong evidence that determinants of angiogenesis (e.g. vascular endothelial growth factor) are strongly associated with disease progression. One of the reasons for these outcomes may be our poor understanding of the biology of angiogenesis in prostate cancer (and probably other cancers as well) resulting in inhibition of both detrimental and favourable molecules. We discuss here novel targeted and more specific approaches to inhibit angiogenesis in prostate cancer as well as a completely new therapeutic modality to do this - modulation of alternative splicing - that may be applicable to other molecules/biological processes as well. PMID- 26995306 TI - Pharmacological targeting of redox regulation systems as new therapeutic approach for psychiatric disorders: A literature overview. AB - Redox dysregulation occurs following a disequilibrium between reactive oxygen species (ROS) producing and degrading systems, i.e. mitochondria, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and nitric oxide synthase (NOS) on one hand and the principal antioxidant system, the glutathione, on the other hand. Increasing recent evidence points towards a pathogenetic role of an altered redox state in the development of several mental disorders, such as anxiety, bipolar disorders, depression, psychosis, autism and post-traumaticstress disorders (PTSD). In this regard, pharmacological targeting of the redox state regulating systems in the brain has been proposed as an innovative and promising therapeutic approach for the treatment of these mental diseases. This review will summarize current knowledge obtained from both pre-clinical and clinical studies in order to descant "lights and shadows" of targeting pharmacologically both the producing and degrading reactive oxygen species (ROS) systems in psychiatric disorders. PMID- 26995307 TI - The challenges of treating epilepsy with 25 antiepileptic drugs. AB - Nowadays a substantial armamentarium of antiepileptic drugs (AEDs) is available, including drugs with different mechanisms of action, pharmacokinetics, efficacy and tolerability; therefore the choice for the right treatment is often challenging. The specific characteristic of the drug, the epileptic syndrome, seizure types and the patient's features need to be taken into consideration driving the choice through available evidence-based studies, which are often lacking for older AEDs. Besides, study conditions in registered clinical trials (RCTs) are quite different from daily clinical practice, which is more complex and various. When dealing with first diagnosed epilepsy, monotherapy is widely accepted as the gold standard option. Likewise, alternative monotherapy should be considered when the first drug treatment fails. However, the association of different AEDs in polytherapy is a common practice. The choice of AEDs used in association is often based on clinical experience or anecdotal observations or small clinical studies. Polytherapy should be as "rational" as possible and consider the mechanism of action, the pharmacokinetic characteristics and the safety of each drug. When dealing with drug resistant patients, clinicians should never give up and consider the use of AEDs acting on new targets. An attempt to come back to a monotherapy or simpler therapeutic regimen should be pursued even in patients who were previously drug resistant. This review will focus on the strategies to treat epilepsy by choosing among 25 available drugs. PMID- 26995308 TI - Learning and sleep-dependent consolidation of spatial and procedural memories are unaltered in young men under a fixed short sleep schedule. AB - OBJECTIVE: To investigate if a fixed short sleep schedule impairs one of the main functions of sleep, which is to consolidate newly learned memories. METHODS: Sixteen young men participated in two experimental conditions, each of which lasted for 3 consecutive days and nights in our laboratory: a short sleep schedule (4.25-h sleep opportunity per night) versus a normal sleep schedule (8.5h per night). In the evening after two experimental nights, participants learned locations of 15 card pairs (spatial memory task) and a procedural finger tapping sequence task. Post-sleep retrieval of both memory tasks was tested the next morning. RESULTS: The short sleep schedule, compared with the normal sleep schedule, considerably altered sleep characteristics, e.g. the proportion of time in slow-wave sleep increased across the three experimental nights. In contrast, neither learning in the evening of day 2, nor subsequent overnight memory consolidation (i.e. concerning the change in memory performance between pre-sleep learning on day 2 and post-sleep retrieval on day 3) differed between the normal and short sleep schedule conditions. CONCLUSIONS: Our findings suggest that learning in the evening and subsequent sleep-dependent consolidation of procedural and spatial memories are unaltered in young men living under a fixed short sleep schedule. Future studies are warranted to validate our findings in other groups (e.g. adolescents and older subjects) and after more prolonged chronic sleep loss paradigms. PMID- 26995309 TI - Immediate extinction promotes the return of fear. AB - Accumulating evidence indicates that immediate extinction is less effective than delayed extinction in attenuating the return of fear. This line of fear conditioning research impacts the proposed onset of psychological interventions after threatening situations. In the present study, forty healthy men were investigated in a differential fear conditioning paradigm with fear acquisition in context A, extinction in context B, followed by retrieval testing in both contexts 24h later to test fear renewal. Differently coloured lights served as conditioned stimuli (CS): two CS (CS+) were paired with an electrical stimulation that served as unconditioned stimulus, the third CS was never paired (CS-). Extinction took place immediately after fear acquisition or 24h later. One CS+ was extinguished whereas the second CS+ remained unextinguished to control for different time intervals between fear acquisition and retrieval testing. Immediate extinction led to larger skin conductance responses during fear retrieval to both the extinguished and unextinguished CS relative to the CS-, indicating a stronger return of fear compared to delayed extinction. Taken together, immediate extinction is less potent than delayed extinction and is associated with a stronger renewal effect. Thus, the time-point of psychological interventions relative to the offset of threatening situations needs to be carefully considered to prevent relapses. PMID- 26995310 TI - Differential regional responsiveness of astroglia in mild hepatic encephalopathy: An Immunohistochemical approach in bile duct ligated rat. AB - Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. However, the pathomechanisms of the disease remains obscure. Neuropathological studies have demonstrated a primary gliopathy in humans as well as in animal models of chronic and acute liver failure. Here, we have investigated in an animal model of mild HE: the bile duct ligated rat (BDL) at the cirrhotic stage (4 weeks after surgery), the expression of the key marker of mature astrocytes; the glial fibrillary acidic protein (GFAP) in different brain areas such as: Substantia nigra pars compacta (SNc), Ventral tegmental area (VTA), hippocampus, dorsal striatum and brain cortex by means of immunohistochemistry. The immunohistochemical study showed, in BDL compared to the operated controls (shams), a diminished astrocyte reactivity corresponding to a loss of GFAP expression within SNc, VTA, hippocampus and dorsal striatum (p<0.05),whereas in the brain cortex astrocytes appeared strongly immunoreactive with increased GFAP expression (p<0.05) as compared to shams. Our finding demonstrated differential astroglial responses which depend to the specificity of the area investigated and its particular neuronal neighboring environment, and could have possible outcomes on the diverse neuronal functions especially those observed during the different episodes of hepatic encephalopathy. PMID- 26995311 TI - Manganese-induced regulations in growth, yield formation, quality characters, rice aroma and enzyme involved in 2-acetyl-1-pyrroline biosynthesis in fragrant rice. AB - Micro-nutrient application is essential for normal plant growth while a little is known about manganese (Mn)-induced regulations in morpho-physiological attributes, aroma formation and enzyme involved in 2-acetyl-1-pyrroline (2-AP) biosynthesis in aromatic rice. Present study aimed to examine the influence of four levels of Mn i.e., Mn1 (100 mg MnSO4 pot(-1)), Mn2 (150 mg MnSO4 pot(-1)), Mn3 (200 mg MnSO4 pot(-1)), and Mn4 (250 mg MnSO4 pot(-1)) on the growth, yield formation, quality characters, rice aroma and enzyme involved in 2-acetyl-1 pyrroline biosynthesis in two fragrant rice cultivars i.e., Meixiangzhan and Nongxiang 18. Pots without Mn application were served as control (Ck). Each pot contained 15 kg of soil. Effects on agronomic characters, quality attributes, 2 AP contents and enzymes involved in 2-AP biosynthesis have been studied in early and late season rice. Results depicted that Mn improved rice growth, yield and related characters, and some quality attributes significantly. It further up regulated proline, pyrroline-5-carboxylic acid (P5C) (precursors of 2-AP), soluble proteins and activities of proline dehydrogenase (ProDH), Delta(1) pyrroline-5-carboxylic acid synthetase (P5CS) ornithine aminotransferase (OAT) that led to enhanced 2-AP production in rice grains. Moreover, higher Mn levels resulted in increased grain Mn contents in both rice cultivars. Along with growth and yield improvement, Mn application significantly improved rice aromatic contents. Overall, Nongxiang 18 accumulated more 2-AP contents than Meixiangzhan in both seasons under Mn application. This study further explored the importance of Mn in rice aroma formation and signifies that micro-nutrients can play significant roles in rice aroma synthesis; however, intensive studies at molecular levels are still needed to understand the exact mechanisms of Mn to improve rice aroma formation. PMID- 26995312 TI - Evidences for growth-promoting and fungicidal effects of low doses of tricyclazole in barley. AB - The effect of increasing concentrations (5-100 mg L(-1)) of tricyclazole (TCZ), an important fungicide commonly used for control of spot blotch disease, was investigated for changes in physiological and biochemical parameters in 10 and 20 days-old barley plants (Hordeum vulgare L., cv. RD-2508). A 10 mg L(-1) dose of TCZ supplemented with nutrient solution in barley plants reflected a lowered infection with a significant increase in plant growth, plant biomass, leaf chlorophyll level, altered reactive oxygen species (ROS) formation and altered activity of key antioxidant enzymes viz. superoxide dismutase (SOD, EC: 1.15.1.1), catalase (CAT, EC: 1.11.1.6), ascorbate peroxidase (APX, EC: 1.11.1.1) and guaiacol peroxidase (GPX, EC: 1.11.1.7). To our knowledge this is the first report that provides evidence for TCZ to act both as a fungicide as well as to have plant growth-promoting activity. The study suggests that this dual property of tricyclazole has a potential for integration in disease management programs in barley. Application of low doses of TCZ can fit in well with environment friendly strategies for sustainable barley crop production, more yield and minimal soil contamination. PMID- 26995313 TI - Anthocyanins and flavonols are responsible for purple color of Lablab purpureus (L.) sweet pods. AB - Lablab pods, as dietary vegetable, have high nutritional values similar to most of edible legumes. Moreover, our studies confirmed that purple lablab pods contain the natural pigments of anthocyanins and flavonols. Compared to green pods, five kinds of anthocyanins (malvidin, delphinidin and petunidin derivatives) were found in purple pods by HPLC-ESI-MS/MS and the major contents were delphinidin derivatives. Besides, nine kinds of polyphenol derivatives (quercetin, myricetin, kaempferol and apigenin derivatives) were detected by UPLC ESI-MS/MS and the major components were quercetin and myricetin derivatives. In order to discover their molecular mechanism, expression patterns of biosynthesis and regulatory gens of anthocyanins and flavonols were investigated. Experimental results showed that LpPAL, LpF3H, LpF3'H, LpDFR, LpANS and LpPAP1 expressions were significantly induced in purple pods compared to green ones. Meanwhile, transcripts of LpFLS were more abundant in purple pods than green or yellow ones, suggestind that co-pigments of anthocyanins and flavonols are accumulated in purple pods. Under continuously dark condition, no anthocyanin accumulation was detected in purple pods and transcripts of LpCHS, LpANS, LpFLS and LpPAP1 were remarkably repressed, indicating that anthocyanins and flavonols biosynthesis in purple pods was regulated in light-dependent manner. These results indicate that co-pigments of anthocyanins and flavonols contribute to purple pigmentations of pods. PMID- 26995314 TI - A combined application of biochar and phosphorus alleviates heat-induced adversities on physiological, agronomical and quality attributes of rice. AB - Present study examined the influence of high-temperature stress and different biochar and phosphorus (P) fertilization treatments on the growth, grain yield and quality of two rice cultivars (IR-64 and Huanghuazhan). Plants were subjected to high day temperature-HDT (35 degrees C +/- 2), high night temperature-HNT (32 degrees C +/- 2), and control temperature-CT (28 degrees C +/- 2) in controlled growth chambers. The different fertilization treatments were control, biochar alone, phosphorous (P) alone and biochar + P. High-temperature stress severely reduced the photosynthesis, stomatal conductance, water use efficiency, and increased the leaf water potential of both rice cultivars. Grain yield and its related attributes except for number of panicles, were reduced under high temperature. The HDT posed more negative effects on rice physiological attributes, while HNT was more destructive for grain yield. High temperature stress also hampered the grain appearance and milling quality traits in both rice cultivars. The Huanghuazhan performed better than IR-64 under high-temperature stress with better growth and higher grain yield. Different soil fertilization treatments were helpful in ameliorating the detrimental effects of high temperature. Addition of biochar alone improved some growth and yield parameters but such positive effects were lower when compared with the combined application of biochar and P. The biochar+P application recorded 7% higher grain yield (plant(-1)) of rice compared with control averaged across different temperature treatments and cultivars. The highest grain production and better grain quality in biochar+P treatments might be due to enhanced photosynthesis, water use efficiency, and grain size, which compensated the adversities of high temperature stress. PMID- 26995315 TI - Factors Associated With Participation in a University Worksite Wellness Program. AB - INTRODUCTION: Healthcare reform legislation encourages employers to implement worksite wellness activities as a way to reduce rising employer healthcare costs. Strategies for increasing program participation is of interest to employers, though few studies characterizing participation exist in the literature. The University of Michigan conducted a 5-year evaluation of its worksite wellness program, MHealthy, in 2014. MHealthy elements include Health Risk Assessment, biometric screening, a physical activity tracking program (ActiveU), wellness activities, and participation incentives. METHODS: Individual-level data were obtained for a cohort of 20,237 employees who were continuously employed by the university all 5 years. Multivariate logistic regression was used to assess the independent predictive power of characteristics associated with participation in the Health Risk Assessment, ActiveU, and incentive receipt, including employee and job characteristics, as well as baseline (2008) healthcare spending and health diagnoses obtained from claims data. Data were collected from 2008 to 2013; analyses were conducted in 2014. RESULTS: Approximately half of eligible employees were MHealthy participants. A consistent profile emerged for Health Risk Assessment and ActiveU participation and incentive receipt with female, white, non-union staff and employees who seek preventive care among the most likely to participate in MHealthy. CONCLUSIONS: This study helps characterize employees who choose to engage in worksite wellness programs. Such information could be used to better target outreach and program content and reduce structural barriers to participation. Future studies could consider additional job characteristics, such as job type and employee attitudinal variables regarding health status and wellness program effectiveness. PMID- 26995317 TI - The blood-brain barrier in systemic inflammation. AB - The blood-brain barrier (BBB) plays a key role in maintaining the specialized microenvironment of the central nervous system (CNS), and enabling communication with the systemic compartment. BBB changes occur in several CNS pathologies. Here, we review disruptive and non-disruptive BBB changes in systemic infections and other forms of systemic inflammation, and how these changes may affect CNS function in health and disease. We first describe the structure and function of the BBB, and outline the techniques used to study the BBB in vitro, and in animal and human settings. We then summarise the evidence from a range of models linking BBB changes with systemic inflammation, and the underlying mechanisms. The clinical relevance of these BBB changes during systemic inflammation are discussed in the context of clinically-apparent syndromes such as sickness behaviour, delirium, and septic encephalopathy, as well as neurological conditions such as Alzheimer's disease and multiple sclerosis. We review emerging evidence for two novel concepts: (1) a heightened sensitivity of the diseased, versus healthy, BBB to systemic inflammation, and (2) the contribution of BBB changes induced by systemic inflammation to progression of the primary disease process. PMID- 26995316 TI - Parental support buffers the association of depressive symptoms with cortisol and C-reactive protein during adolescence. AB - Social experiences can affect the relationship between depression and physical health. The current study examined how social support from parents and friends may moderate the association of depressive symptoms with hypothalamic-pituitary adrenal (HPA) axis activity and C-reactive protein among adolescents (N=316, Mage=16.40, SD=.74; 57% female) from diverse ethnic backgrounds (23.1% Asian, 29.1% European, 41.8% Latino, and 6.0% other backgrounds). Results indicated that parent support, but not friend support, moderated the link between depressive symptoms and both total daily cortisol output (a measure HPA activity) and C reactive protein (a marker of inflammation). These patterns did not differ by ethnicity. Overall, the study highlights the continued, and perhaps accumulated, importance of parents during adolescence despite increasing needs for autonomy from and exploration outside of the family unit. PMID- 26995318 TI - Genome scale metabolic reconstruction of Chlorella variabilis for exploring its metabolic potential for biofuels. AB - A compartmentalized genome scale metabolic network was reconstructed for Chlorella variabilis to offer insight into various metabolic potentials from this alga. The model, iAJ526, was reconstructed with 1455 reactions, 1236 metabolites and 526 genes. 21% of the reactions were transport reactions and about 81% of the total reactions were associated with enzymes. Along with gap filling reactions, 2 major sub-pathways were added to the model, chitosan synthesis and rhamnose metabolism. The reconstructed model had reaction participation of 4.3 metabolites per reaction and average lethality fraction of 0.21. The model was effective in capturing the growth of C. variabilis under three light conditions (white, red and red+blue light) with fair agreement. This reconstructed metabolic network will serve an important role in systems biology for further exploration of metabolism for specific target metabolites and enable improved characteristics in the strain through metabolic engineering. PMID- 26995319 TI - Microalgae as substrate in low cost terracotta-based microbial fuel cells: Novel application of the catholyte produced. AB - In this work, the by-product generated during the operation of cylindrical MFCs, made out of terracotta material, is investigated as a feasible means of degrading live microalgae for the first time. In addition to the low cost materials of this design, the reuse of the solution produced in the cathode renders the technology truly green and capable of generating bioenergy. In this study, the effect of a light/dark cycle or dark conditions only on the digestion of live microalgae with the catholyte is investigated. The results show that a combination of light/dark improves degradation and allows algae to be used as substrate in the anode. The addition of 12.5mL of a 1:1 mix of catholyte and microalgae (pre-digested over 5days under light/dark) to the anode, increases the power generation from 7MUW to 44MUW once all the organic matter in the anode had been depleted. PMID- 26995320 TI - Effects of anti-foaming agents on biohydrogen production. AB - The effects of antifoaming agents on fermentative hydrogen production using galactose in batch and continuous operations were investigated. Batch hydrogen production assays with LS-303 (dimethylpolysiloxane), LG-109 (polyalkylene), LG 126 (polyoxyethylenealkylene), and LG-299 (polyether) showed that the doses and types of antifoaming agents played a significant role in hydrogen production. During batch tests, LS-303 at 100MUL/L resulted in the maximum hydrogen production rate (HPR) and hydrogen yield (HY) of 2.5L/L-d and 1.08mol H2/mol galactoseadded, respectively. The following continuously stirred tank reactor operated at 12h HRT with LS-303 at 100MUL/L showed a stable HPR and HY of 4.9L/L d and 1.17mol H2/mol galactoseadded, respectively, which were higher than those found for the control reactor. Microbial community analysis supported the alterations in H2 generation under different operating conditions and the stimulatory impact of certain antifoaming chemicals on H2 production was demonstrated. PMID- 26995321 TI - Production of poly-3-hydroxybutyrate (P3HB) and poly(3-hydroxybutyrate-co-3 hydroxyvalerate) P(3HB-co-3HV) from synthetic wastewater using Hydrogenophaga palleronii. AB - In the present study, synthetic wastewater (SW) was used for production of poly-3 hydroxybutyrate (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co 3HV) using the bacteria Hydrogenophaga palleronii. SW at various volatile fatty acids concentrations (5-60g/l) was evaluated for the growth and biopolymer production using H. palleronii. Substrate degradation was analyzed using total organic carbon (TOC) analyzer and high pressure liquid chromatography (HPLC). H. palleronii showed highest and lowest removal of TOC at 5g/l (88+/-4%) and 60g/l (15+/-6%) respectively. Among all the concentrations evaluated, bacteria showed highest biopolymer production with 20g/l (63+/-5%), followed by 30g/l (58+/-3%) and 40g/l (56+/-2%). Lowest biopolymer production was observed at 5g/l concentration (21+/-3%). Structure, molecular weight, and thermal properties of the produced biopolymer were analyzed. These results denoted that the strain H. palleronii can be used for degradation of high concentration of volatile fatty acids persistent in wastewaters and their subsequent conversion into useable biopolymers. PMID- 26995322 TI - Recovery of phosphate from aqueous solution by magnesium oxide decorated magnetic biochar and its potential as phosphate-based fertilizer substitute. AB - The present study deals with the preparation of a novel MgO-impregnated magnetic biochar (MMSB) for phosphate recovery from aqueous solution. The MMSB was evaluated against sugarcane harvest residue biochar (SB) and magnetic biochar without Mg (MSB). The results showed that increasing Mg content in MMSB greatly improved the phosphate adsorption compared to SB and MSB, with 20% Mg-impregnated MMSB (20MMSB) recovering more than 99.5% phosphate from aqueous solution. Phosphate adsorption capacity of 20MMSB was 121.25mgP/g at pH 4 and only 37.53% of recovered phosphate was desorbed by 0.01mol/L HCl solutions. XRD and FTIR analysis showed that phosphate sorption mechanisms involved predominately with surface electrostatic attraction and precipitation with impregnated MgO and surface inner-sphere complexation with Fe oxide. The 20MMSB exhibited both maximum phosphate sorption and strong magnetic separation ability. Overall, phosphate-loaded 20MMSB significantly enhanced plant growth and could be used as a potential substitute for phosphate-based fertilizer. PMID- 26995323 TI - Exposure of dogs to spotted fever group rickettsiae in urban sites associated with human rickettsioses in Costa Rica. AB - The zoonotic transmission cycles of Rickettsia rickettsii and other spotted fever group (SFG) rickettsiae in Latin America have usually been associated with rural or sylvatic environments, although domestic dogs can be implicated in more populated settings. In this study, exposure of dogs to SFG rickettsiae in the Greater Metropolitan Area of Costa Rica was investigated. Dogs from sites associated with human cases and from dog shelters were evaluated by indirect immunofluorescence assay (IFA) using antigen of SFG rickettsiae. Rickettsia spp. were detected in ectoparasites by polymerase chain reaction (PCR). A total 18.5% (31/168) of dogs associated with human cases and 6.8% (11/161) of dogs in shelters had IgG end titers>=64 to Rickettsia spp. The odds of being seropositive were greater in dogs from areas associated with human cases when compared to shelters (OR: 3.2; 95% C.I: 1.5-5.6). Rhipicephalus sanguineus sensu lato (s. l.) was present in all sites associated with human cases. Rickettsia felis URRWXCal2 and R. felis-like RF2125 were detected in Ctenocephalides felis, and Rickettsia sp. IbR/CRC in Ixodes boliviensis. Results demonstrate that dogs from the main urban center of Costa Rica have been exposed to SFG rickettsiae, especially in areas with known human infection. Both human and animal health sectors must be aware of possible rickettsial diseases in urban areas, where dogs may also serve as sentinels for human infection. PMID- 26995325 TI - Transport of engineered nanoparticles in partially saturated sand columns. AB - The vadose zone is a critical region controlling fate and transport of contaminants in soils and, ultimately, groundwater. It is therefore important to understand the behavior of engineered nanoparticles (ENPs) in this zone, as a potential group of emerging contaminants. Soil is a significant sink for ENPs; however, only a few studies have considered the fate and transport of ENPs in partially saturated systems, representative of the vadose zone. Here, transport behavior of three commonly used ENPs--gold (Au-NPs), silver (Ag-NPs) and zinc oxide (ZnO-NPs)--is investigated in partially saturated sand columns. High mobilities of Au-NPs and Ag-NPs under different water saturation levels and concentrations were observed. The presence of CaCl2 reduces Ag-NP mobility through chemical interactions, similar to behavior reported in saturated systems. Furthermore, transformation of Ag-NPs in the environment may influence their mobility; aging of Ag-NPs following sulfidation was investigated. The silver sulfide (Ag2S-NPs) remained stable in aqueous suspension, and mobile in the partially saturated sand column. In contrast, the positively-charged ZnO-NPs were completely immobilized in the sand column. Significantly, though, addition of humic acid (HA) to the ZnO-NP suspension reverses particle surface charge and thus increases their mobility. Moreover, remobilization of entrapped ZnO-NPs by HA was demonstrated. PMID- 26995326 TI - Viral hepatitis and immigration: A challenge for the healthcare system. AB - BACKGROUND: Viral hepatitis is a significant health problem in African countries. The increase in the immigrant population from this continent represents a challenge for the Spanish healthcare system. MATERIAL AND METHODS: A descriptive study was conducted on the prevalence of the serological markers of hepatitis B (HBV), C (HCV) and D (HDV) in African immigrants treated in a specialised doctor's office. RESULTS: The study included 2518 patients (87.7% Sub-Saharan natives), with a mean age of 31.3 years. Some 78.8% of the patients had a positive infection marker for HBV, and 638 patients (25.3%) were diagnosed with active hepatitis B (HBsAg +). In 19 cases, antibodies against HDV were detected (4 cases with detection of the viral genome). Sixty-eight patients had antibodies against HCV, 26 of whom had a positive viral load. CONCLUSIONS: The high prevalence of viral hepatitis in immigrants, especially HBV infection, represents a significant change in the profile of patients treated in Spain and requires measures aimed at early diagnosis and transmission prevention. PMID- 26995324 TI - Impact of rapamycin on status epilepticus induced hippocampal pathology and weight gain. AB - Growing evidence implicates the dentate gyrus in temporal lobe epilepsy (TLE). Dentate granule cells limit the amount of excitatory signaling through the hippocampus and exhibit striking neuroplastic changes that may impair this function during epileptogenesis. Furthermore, aberrant integration of newly generated granule cells underlies the majority of dentate restructuring. Recently, attention has focused on the mammalian target of rapamycin (mTOR) signaling pathway as a potential mediator of epileptogenic change. Systemic administration of the mTOR inhibitor rapamycin has promising therapeutic potential, as it has been shown to reduce seizure frequency and seizure severity in rodent models. Here, we tested whether mTOR signaling facilitates abnormal development of granule cells during epileptogenesis. We also examined dentate inflammation and mossy cell death in the dentate hilus. To determine if mTOR activation is necessary for abnormal granule cell development, transgenic mice that harbored fluorescently-labeled adult-born granule cells were treated with rapamycin following pilocarpine-induced status epilepticus. Systemic rapamycin effectively blocked phosphorylation of S6 protein (a readout of mTOR activity) and reduced granule cell mossy fiber axon sprouting. However, the accumulation of ectopic granule cells and granule cells with aberrant basal dendrites was not significantly reduced. Mossy cell death and reactive astrocytosis were also unaffected. These data suggest that anti-epileptogenic effects of mTOR inhibition may be mediated by mechanisms other than inhibition of these common dentate pathologies. Consistent with this conclusion, rapamycin prevented pathological weight gain in epileptic mice, suggesting that rapamycin might act on central circuits or even peripheral tissues controlling weight gain in epilepsy. PMID- 26995327 TI - Magnetic Resonance and Ultrasound Image Fusion Supported Transperineal Prostate Biopsy Using the Ginsburg Protocol: Technique, Learning Points, and Biopsy Results. AB - BACKGROUND: Prostate biopsy supported by transperineal image fusion has recently been developed as a new method to the improve accuracy of prostate cancer detection. OBJECTIVE: To describe the Ginsburg protocol for transperineal prostate biopsy supported by multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) image fusion, provide learning points for its application, and report biopsy results. The article is supplemented by a Surgery in Motion video. DESIGN, SETTING, AND PARTICIPANTS: This single-centre retrospective outcome study included 534 patients from March 2012 to October 2015. A total of 107 had no previous prostate biopsy, 295 had benign TRUS-guided biopsies, and 159 were on active surveillance for low-risk cancer. SURGICAL PROCEDURE: A Likert scale reported mpMRI for suspicion of cancer from 1 (no suspicion) to 5 (cancer highly likely). Transperineal biopsies were obtained under general anaesthesia using BiopSee fusion software (Medcom, Darmstadt, Germany). All patients had systematic biopsies, two cores from each of 12 anatomic sectors. Likert 3-5 lesions were targeted with a further two cores per lesion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Any cancer and Gleason score 7-10 cancer on biopsy were noted. Descriptive statistics and positive predictive values (PPVs) and negative predictive values (NPVs) were calculated. RESULTS AND LIMITATIONS: The detection rate of Gleason score 7-10 cancer was similar across clinical groups. Likert scale 3-5 MRI lesions were reported in 378 (71%) of the patients. Cancer was detected in 249 (66%) and Gleason score 7-10 cancer was noted in 157 (42%) of these patients. PPV for detecting 7-10 cancer was 0.15 for Likert score 3, 0.43 for score 4, and 0.63 for score 5. NPV of Likert 1-2 findings was 0.87 for Gleason score 7-10 and 0.97 for Gleason score >=4+3=7 cancer. Limitations include lack of data on complications. CONCLUSIONS: Transperineal prostate biopsy supported by MRI/TRUS image fusion using the Ginsburg protocol yielded high detection rates of Gleason score 7-10 cancer. Because the NPV for excluding Gleason score 7-10 cancer was very high, prostate biopsies may not be needed for all men with elevated prostate-specific antigen values and nonsuspicious mpMRI. PATIENT SUMMARY: We present our technique to sample (biopsy) the prostate by the transperineal route (the area between the scrotum and the anus) to detect prostate cancer using a fusion of magnetic resonance and ultrasound images to guide the sampling. PMID- 26995329 TI - Reply to Stephen B. Williams and John F. Ward's Letter to the Editor re: Jan P. Radtke, Constantin Schwab, Maya B. Wolf, et al. Multiparametric Magnetic Resonance Imaging (MRI) and MRI-Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.12.052. PMID- 26995330 TI - Reply to Valerian Ciprian Lucan, Salvatore Buttice, Rosa Pappalardo, Carlo Magno's Letter to the Editor re: Mark W. Ball, Nathaniel Readal, Phillip M. Pierorazio, Mohamad E. Allaf. Splitting One Kidney into Two: Robotic Partial Kidney Transplant in a Porcine Model. Eur Urol 2016;69:968-9. PMID- 26995328 TI - Impact of Prostate-specific Antigen (PSA) Screening Trials and Revised PSA Screening Guidelines on Rates of Prostate Biopsy and Postbiopsy Complications. AB - BACKGROUND: Prostate biopsy and postbiopsy complications represent important risks of prostate-specific antigen (PSA) screening. Although landmark randomized trials and updated guidelines have challenged routine PSA screening, it is unclear whether these publications have affected rates of biopsy or postbiopsy complications. OBJECTIVE: To evaluate whether publication of the 2008 and 2012 US Preventive Services Task Force (USPSTF) recommendations, the 2009 European Randomized Study of Screening for Prostate Cancer and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or the 2013 American Urological Association (AUA) guidelines was associated with changes in rates of biopsy or postbiopsy complications, and to identify predictors of postbiopsy complications. DESIGN, SETTING, AND PARTICIPANTS: This quasiexperimental study used administrative claims of 5279315 commercially insured US men aged >=40 yr from 2005 to 2014, of whom 104584 underwent biopsy. INTERVENTIONS: Publications on PSA screening. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Interrupted time-series analysis was used to evaluate the association of publications with rates of biopsy and 30-d complications. Logistic regression was performed to identify predictors of complications. RESULTS AND LIMITATIONS: From 2005 to 2014, biopsy rates fell 33% from 64.1 to 42.8 per 100000 person-months, with immediate reductions following the 2008 USPSTF recommendations (-10.1; 95% confidence interval [CI], -17.1 to -3.0; p<0.001), 2012 USPSTF recommendations (-13.8; 95% CI, -21.0 to -6.7; p<0 .001), and 2013 AUA guidelines (-8.8; 95% CI, -16.7 to 0.92; p=0.03). Concurrently, complication rates decreased 10% from 8.7 to 7.8 per 100000 person-months, with a reduction following the 2012 USPSTF recommendations (-2.5; 95% CI, -4.5 to -0.45; p=0.02). However, the proportion of men undergoing biopsy who experienced complications increased from 14% to 18%, driven by nonsepsis infectious complications (p<0.001). Predictors of complications included prior fluoroquinolone use (odds ratio [OR]: 1.27; 95% CI, 1.22-1.32; p<0.001), anticoagulant use (OR: 1.14; 95% CI, 1.04-1.25; p=0.004), and age >=70 yr (OR: 1.25; 95% CI, 1.15-1.36; p<0.001). Limitations included the retrospective design. CONCLUSIONS: Although there has been an absolute reduction in rates of biopsy and 30-d complications, the relative morbidity of biopsy continues to increase. These observations suggest a need to reduce the morbidity of biopsy. PATIENT SUMMARY: Absolute rates of biopsy and postbiopsy complications have decreased following landmark publications about prostate-specific antigen screening; however, the relative morbidity of biopsy continues to increase. PMID- 26995331 TI - Re: Hiury S. Andrade, Homayoun Zargar, Peter A. Caputo, et al. Five-year Oncologic Outcomes After Transperitoneal Robotic Partial Nephrectomy for Renal Cell Carcinoma. Eur Urol 2016;69:1149-54. PMID- 26995332 TI - Next-generation sequencing (NGS) in the microbiological world: How to make the most of your money. AB - The Sanger sequencing method produces relatively long DNA sequences of unmatched quality and has been considered for long time as the gold standard for sequencing DNA. Many improvements of the Sanger method that culminated with fluorescent dyes coupled with automated capillary electrophoresis enabled the sequencing of the first genomes. Nevertheless, using this technology to sequence whole genomes was costly, laborious and time consuming even for genomes that are relatively small in size. A major technological advance was the introduction of next-generation sequencing (NGS) pioneered by 454 Life Sciences in the early part of the 21th century. NGS allowed scientists to sequence thousands to millions of DNA molecules in a single machine run. Since then, new NGS technologies have emerged and existing NGS platforms have been improved, enabling the production of genome sequences at an unprecedented rate as well as broadening the spectrum of NGS applications. The current affordability of generating genomic information, especially with microbial samples, has resulted in a false sense of simplicity that belies the fact that many researchers still consider these technologies a black box. In this review, our objective is to identify and discuss four steps that we consider crucial to the success of any NGS-related project. These steps are: (1) the definition of the research objectives beyond sequencing and appropriate experimental planning, (2) library preparation, (3) sequencing and (4) data analysis. The goal of this review is to give an overview of the process, from sample to analysis, and discuss how to optimize your resources to achieve the most from your NGS-based research. Regardless of the evolution and improvement of the sequencing technologies, these four steps will remain relevant. PMID- 26995333 TI - The role of time delay in adaptive cellular negative feedback systems. AB - Adaptation in cellular systems is often mediated by negative feedbacks, which usually come with certain time delays causing several characteristic response patterns including an overdamped response, damped or sustained oscillations. Here, we analyse generic two-dimensional delay differential equations with delayed negative feedback describing the dynamics of biochemical adaptive signal response networks. We derive explicit thresholds and boundaries showing how time delay determines characteristic response patterns of these networks. Applying our theoretical analyses to concrete data we show that adaptation to osmotic stress in yeast is optimal in the sense of minimizing adaptation time without causing oscillatory behaviour, i.e., a critically damped response. In addition, our framework demonstrates that a slight increase of time delay in the NF-kappaB system might induce a switch from damped to sustained oscillatory behaviour. Thus, we demonstrate how delay differential equations can be used to explicitly study the delay in biochemical negative feedback systems. Our analysis also provides insight into how time delay may tune biological signal-response patterns and control the systems behaviour. PMID- 26995334 TI - Survivin, caspase-3 and MIB-1 expression in astrocytic tumors of various grades. AB - PURPOSE: Gliomas are the most common primary brain tumors. The etiology is still unclear and the progression from low to high-grade gliomas is frequent. The molecular mechanisms are quite established, however the heterogeneity of glioblastomas force the scientist to look for the new therapeutic targets. The aim of the study was to evaluate the caspase-3 and survivin expression in correlation with MIB-1 expression in gliomas of various grade to assess the apoptosis in gliomas and to determinate new possible targets for the future therapy. MATERIAL AND METHODS: We identified 131 patients with a histopathological diagnosis of astrocytic tumors (diffuse astrocytoma, anaplastic astrocytoma and glioblastoma). The evaluation of caspase-3, survivin and MIB-1 expression was done using immunohistochemical methods. RESULTS: Caspase-3 and survivin expression was observed both in low- and high-grade astrocytomas. The differences in expression were the most evident in glioblastoma group. All primary glioblastomas (31 cases) expressed caspase-3. In secondary glioblastoma group only 17 out of 30 specimens were positive for caspase-3. Survivin expression was observed in 80.6% primary glioblastomas and in all examined secondary glioblastomas and the staining was strong and diffuse in all cases. MIB 1 expression was low in diffuse astrocytomas (DA) and ranged between 1 and 5%. In anaplastic astrocytoma group it was ranged between 5 and 10% and the highest percentage of the positive cells was observed in glioblastoma cases and ranged from 10% even to 30%. The most evident MIB-1 expression was observed in the cells surrounding the pathological blood vessels and necrosis. CONCLUSIONS: The high incidence of survivin and caspase-3 expression in diffuse and anaplastic astrocytoma cases may suggest, that the regulation between pro- and antiapoptotic proteins may play an important role in tumor growth and progression. The overexpression of survivin and MIB-1 expression in glioblastoma cases also may confirm the theory about the important role of anti-apoptotic and proliferation processes in glioblastoma progression and as such may be potential therapeutic targets. PMID- 26995336 TI - Cranial Suture Closure in Domestic Dog Breeds and Its Relationships to Skull Morphology. AB - Bulldog-type brachycephalic domestic dog breeds are characterized by a relatively short and broad skull with a dorsally rotated rostrum (airorhynchy). Not much is known about the association between a bulldog-type skull conformation and peculiar patterns of suture and synchondrosis closure in domestic dogs. In this study, we aim to explore breed-specific patterns of cranial suture and synchondrosis closure in relation to the prebasial angle (proxy for airorhynchy and thus bulldog-type skull conformation) in domestic dogs. For this purpose, we coded closure of 18 sutures and synchondroses in 26 wolves, that is, the wild ancestor of all domestic dogs, and 134 domestic dogs comprising 11 breeds. Comparisons of the relative amount of closing and closed sutures and synchondroses (closure scores) in adult individuals showed that bulldog-type breeds have significantly higher closure scores than non-bulldog-type breeds and that domestic dogs have significantly higher closure scores than the wolf. We further found that the prebasial angle is significantly positively correlated with the amount of closure of the basispheno-presphenoid synchondrosis and sutures of the nose (premaxillo-nasal and maxillo-nasal) and the palate (premaxillo-maxillary and interpalatine). Our results show that there is a correlation between patterns of suture and synchondrosis closure and skull shape in domestic dogs, although the causal relationships remain elusive. PMID- 26995335 TI - Validation of a Clinical Scoring System for Outcome Prediction in Dogs with Acute Kidney Injury Managed by Hemodialysis. AB - BACKGROUND: A scoring system for outcome prediction in dogs with acute kidney injury (AKI) recently has been developed but has not been validated. HYPOTHESIS: The scoring system previously developed for outcome prediction will accurately predict outcome in a validation cohort of dogs with AKI managed with hemodialysis. ANIMALS: One hundred fifteen client-owned dogs with AKI. METHODS: Medical records of dogs with AKI treated by hemodialysis between 2011 and 2015 were reviewed. Dogs were included only if all variables required to calculate the final predictive score were available, and the 30-day outcome was known. A predictive score for 3 models was calculated for each dog. Logistic regression was used to evaluate the association of the final predictive score with each model's outcome. Receiver operating curve (ROC) analyses were performed to determine sensitivity and specificity for each model based on previously established cut-off values. RESULTS: Higher scores for each model were associated with decreased survival probability (P < .001). Based on previously established cut-off values, 3 models (models A, B, C) were associated with sensitivities/specificities of 73/75%, 71/80%, and 75/86%, respectively, and correctly classified 74-80% of the dogs. CONCLUSIONS AND CLINICAL RELEVANCE: All models were simple to apply and allowed outcome prediction that closely corresponded with actual outcome in an independent cohort. As expected, accuracies were slightly lower compared with those from the previously reported cohort used initially to develop the models. PMID- 26995337 TI - The Digestive Tract and Derived Primordia Differentiate by Following a Precise Timeline in Human Embryos Between Carnegie Stages 11 and 13. AB - The precise mechanisms through which the digestive tract develops during the somite stage remain undefined. In this study, we examined the morphology and precise timeline of differentiation of digestive tract-derived primordia in human somite-stage embryos. We selected 37 human embryos at Carnegie Stage (CS) 11-CS13 (28-33 days after fertilization) and three-dimensionally analyzed the morphology and positioning of the digestive tract and derived primordia in all samples, using images reconstructed from histological serial sections. The digestive tract was initially formed by a narrowing of the yolk sac, and then several derived primordia such as the pharynx, lung, stomach, liver, and dorsal pancreas primordia differentiated during CS12 (21-29 somites) and CS13 (>= 30 somites). The differentiation of four pairs of pharyngeal pouches was complete in all CS13 embryos. The respiratory primordium was recognized in >= 26-somite embryos and it flattened and then branched at CS13. The trachea formed and then elongated in >= 35-somite embryos. The stomach adopted a spindle shape in all >= 34-somite embryos, and the liver bud was recognized in >= 27-somite embryos. The dorsal pancreas appeared as definitive buddings in all but three CS13 embryos, and around these buddings, the small intestine bent in >= 33-somite embryos. In >= 35 somite embryos, the small intestine rotated around the cranial-caudal axis and had begun to form a primitive intestinal loop, which led to umbilical herniation. These data indicate that the digestive tract and derived primordia differentiate by following a precise timeline and exhibit limited individual variations. PMID- 26995338 TI - Diverse phenotypic and genetic responses to short-term selection in evolving Escherichia coli populations. AB - Beneficial mutations fuel adaptation by altering phenotypes that enhance the fit of organisms to their environment. However, the phenotypic effects of mutations often depend on ecological context, making the distribution of effects across multiple environments essential to understanding the true nature of beneficial mutations. Studies that address both the genetic basis and ecological consequences of adaptive mutations remain rare. Here, we characterize the direct and pleiotropic fitness effects of a collection of 21 first-step beneficial mutants derived from naive and adapted genotypes used in a long-term experimental evolution of Escherichia coli. Whole-genome sequencing was able to identify the majority of beneficial mutations. In contrast to previous studies, we find diverse fitness effects of mutations selected in a simple environment and few cases of genetic parallelism. The pleiotropic effects of these mutations were predominantly positive but some mutants were highly antagonistic in alternative environments. Further, the fitness effects of mutations derived from the adapted genotypes were dramatically reduced in nearly all environments. These findings suggest that many beneficial variants are accessible from a single point on the fitness landscape, and the fixation of alternative beneficial mutations may have dramatic consequences for niche breadth reduction via metabolic erosion. PMID- 26995339 TI - CORRIGENDUM. PMID- 26995340 TI - Retraction: What determines sex roles in mate searching? Kokko and Wong (2007). PMID- 26995349 TI - Hidden suppression of sex ratio distortion suggests Red queen dynamics between Wolbachia and its dwarf spider host. AB - Genetic conflict theory predicts strong selection for host nuclear factors suppressing endosymbiont effects on reproduction; however, evidence of these suppressors is currently scarce. This can either be caused by a low suppressor evolution rate, or if suppressors originate frequently, by rapid spread and concurrent masking of their activity by silencing the endosymbiont effect. To explore this, we use two populations of a dwarf spider with a similar female bias, caused by a Wolbachia infection. Using inter- and intrapopulation crosses, we determine that one of these populations demonstrates a higher suppressing capability towards Wolbachia despite having a similar population sex ratio. This suggests that spider and endosymbiont are locked in so-called red queen dynamics where, despite continuous coevolution, average fitness remains the same, hence hiding the presence of the suppressor. Finding different suppressor activity in populations that even lack phenotypic differentiation (i.e. similar sex ratio) further supports the hypothesis that suppressors originate often, but are often hidden by their own mode of action by countering endosymbiont effects. PMID- 26995350 TI - Short-term exposure to air pollution and morbidity of COPD and asthma in East Asian area: A systematic review and meta-analysis. AB - BACKGROUND: The association between short-term exposure to air pollution and morbidity of COPD and asthma has been observed in many studies. However, there is a lack of systematic review of the overall risk ratios in East Asian area to provide scientific evidence for health risk assessment. METHODS: A systematic literature retrieval was conducted in December 2014. The results from eligible studies were stratified by pollutants, diseases, types of hospital utilization, and age groups of the subject. For each pollutant-outcome pair, meta-analysis was conducted to calculate the pooled risk ratios (RR) with 95% confidence intervals for every 10MUg/m(3) increase in pollutants (1mg/m(3) in CO). We also performed meta-regression to explore the source of heterogeneity and funnel plots to detect publication bias. RESULTS: Based on results from 26 studies, statistically significant pooled RRs of different pollutants and age groups ranged from 1.007 (SO2 in all ages) to 1.028 (O3 in all ages) for COPD general hospital admissions, 1.011 (SO2 in all ages) to 1.028 (O3 in all ages) for COPD emergency hospital admissions, 1.013 (PM10 in all ages) to 1.141 (CO in children) for all-type asthma hospital utilization, 1.010 (PM10 in all ages) to 1.141 (CO in children) for asthma general hospital admissions, and 1.009 (SO2 in all ages) to 1.040 (NO2 in children) for asthma emergency hospital admissions. The association between air pollution and asthma morbidity was generally stronger in children, but not significant in people aged 15-64. CONCLUSIONS: Evidence was found that short-term exposure to air pollution was associated with increasing risk of hospital utilization for COPD and asthma in the whole population, the elderly and children, but not in people aged 15-64. Children tended to be more susceptible to the effect of air pollution on asthma morbidity. PMID- 26995351 TI - A cloud model-based approach for water quality assessment. AB - Water quality assessment entails essentially a multi-criteria decision-making process accounting for qualitative and quantitative uncertainties and their transformation. Considering uncertainties of randomness and fuzziness in water quality evaluation, a cloud model-based assessment approach is proposed. The cognitive cloud model, derived from information science, can realize the transformation between qualitative concept and quantitative data, based on probability and statistics and fuzzy set theory. When applying the cloud model to practical assessment, three technical issues are considered before the development of a complete cloud model-based approach: (1) bilateral boundary formula with nonlinear boundary regression for parameter estimation, (2) hybrid entropy-analytic hierarchy process technique for calculation of weights, and (3) mean of repeated simulations for determining the degree of final certainty. The cloud model-based approach is tested by evaluating the eutrophication status of 12 typical lakes and reservoirs in China and comparing with other four methods, which are Scoring Index method, Variable Fuzzy Sets method, Hybrid Fuzzy and Optimal model, and Neural Networks method. The proposed approach yields information concerning membership for each water quality status which leads to the final status. The approach is found to be representative of other alternative methods and accurate. PMID- 26995352 TI - RNA Imaging with Dimeric Broccoli in Live Bacterial and Mammalian Cells. AB - RNA spatial dynamics play a crucial role in cell physiology, and thus the ability to monitor RNA localization in live cells can provide insight into important biological problems. This unit focuses on imaging RNAs using an RNA mimic of GFP. This approach relies on an RNA aptamer called dimeric Broccoli, which binds to and switches on the fluorescence of DFHBI, a small molecule mimicking the fluorophore in GFP. Dimeric Broccoli is tagged to heterologously expressed RNAs and, upon DFHBI binding, the fluorescent signal of dimeric Broccoli reports the transcript's localization in cells. This protocol describes the process of validating the fluorescence of dimeric Broccoli--labeled transcripts in vitro and in cells, flow cytometry analysis to determine overall fluorescence levels in cells, and fluorescence imaging in bacterial and mammalian cells. Overall, the protocol should be useful for researchers seeking to image high-abundance RNAs, such as those transcribed off the T7 promoter in bacteria or off Pol III- dependent promoters in mammalian cells. PMID- 26995353 TI - Hollow-Fiber Methodology for Pharmacokinetic/Pharmacodynamic Studies of Antimalarial Compounds. AB - Knowledge of pharmacokinetic/pharmacodynamic (PK/PD) relationships can enhance the speed and economy of drug development by enabling informed and rational decisions at every step, from lead selection to clinical dosing. For anti infective agents in particular, dynamic in vitro hollow-fiber cartridge experiments permit exquisite control of kinetic parameters and the study of their consequent impact on pharmacodynamic efficacy. Such information is of great interest for the cost-restricted but much-needed development of new antimalarial drugs, especially since the major human pathogen Plasmodium falciparum can be cultivated in vitro but is not readily available in animal models. This protocol describes the materials and procedures for determining the PK/PD relationships of antimalarial compounds. PMID- 26995354 TI - Isotope Targeted Glycoproteomics (IsoTaG) to Characterize Intact, Metabolically Labeled Glycopeptides from Complex Proteomes. AB - Protein glycosylation plays many critical roles in biological function and creates the most diversity of all post-translational modifications (PTMs). Glycan structural diversity is directly correlated with difficulty in characterizing the intact glycoproteome by mass spectrometry (MS). In this protocol, we describe a novel mass-independent chemical glycoproteomics platform for characterizing intact, metabolically labeled glycopeptides from complex proteomes, termed Isotope Targeted Glycoproteomics (IsoTaG). To use IsoTaG, cell culture samples are metabolically labeled with an azido- or alkynyl-sugar. Metabolically labeled glycoproteins are then tagged using Click chemistry and enriched with an isotopic recoding biotin probe. Intact glycopeptides are recovered by cleavage of the probe, analyzed with directed MS, and assigned by targeted mass-independent data analysis. The outlined procedure is well defined in cell culture and has been executed with over 15 cell lines. PMID- 26995355 TI - Dual-Level Security based Cyclic18 Steganographic Method and its Application for Secure Transmission of Keyframes during Wireless Capsule Endoscopy. AB - In this paper, the problem of secure transmission of sensitive contents over the public network Internet is addressed by proposing a novel data hiding method in encrypted images with dual-level security. The secret information is divided into three blocks using a specific pattern, followed by an encryption mechanism based on the three-level encryption algorithm (TLEA). The input image is scrambled using a secret key, and the encrypted sub-message blocks are then embedded in the scrambled image by cyclic18 least significant bit (LSB) substitution method, utilizing LSBs and intermediate LSB planes. Furthermore, the cover image and its planes are rotated at different angles using a secret key prior to embedding, deceiving the attacker during data extraction. The usage of message blocks division, TLEA, image scrambling, and the cyclic18 LSB method results in an advanced security system, maintaining the visual transparency of resultant images and increasing the security of embedded data. In addition, employing various secret keys for image scrambling, data encryption, and data hiding using the cyclic18 LSB method makes the data recovery comparatively more challenging for attackers. Experimental results not only validate the effectiveness of the proposed framework in terms of visual quality and security compared to other state-of-the-art methods, but also suggest its feasibility for secure transmission of diagnostically important keyframes to healthcare centers and gastroenterologists during wireless capsule endoscopy. PMID- 26995356 TI - Effect of Anesthesia Staffing Ratio on First-Case Surgical Start Time. AB - On time start of the first case of the day is an important operating room (OR) efficiency metric, in which delays can have effects throughout the day. Although previous studies have identified various causes of first case start delays, none have attempted to evaluate the effect anesthesia staffing ratios have on first case start times. We performed a single-center retrospective analysis at an academic teaching hospital. Data was collected and analyzed over a period of 4 years and on more than 8,700 cases. We examined whether staffing ratios of attending only (solo staffing ratio), attending working with 1 resident/certified registered nurse anesthetist (CRNA) (1 to 1), or attending covering 2 residents/CRNAs (1 to 2) had a significant effect on first patient in room time (FPIR) and first case on time start (FCOTS). In addition, we examined whether staffing ratios had an effect on start times in various surgical subspecialties. We performed a univariate logistic regression analysis to determine if age, anesthesia base units, American Society of Anesthesiologists Physical Status (ASA PS) classification score, and staffing ratio was associated with FPIR and FCOTS being on time. Then, we performed a multivariate logistic regression analysis to determine if staffing ratio was associated with these outcomes, utilizing age, anesthesia base units, and ASA PS class as covariates. A decreased odds for FPIR being on time were seen in general and orthopedic surgeries when staffed 1 to 1, and cardiac surgery when staffed 1 to 2, when compared to solo staffing. FCOTS showed statistically significant differences when looking at all services with solo staffing having the highest odds for FCOTS being on time. This effect was seen also when analyzing only oncologic and orthopedic surgeries. Hospitals should consider using different staffing ratios in different surgical specialties to minimize delays and maximize OR efficiency. PMID- 26995357 TI - Glucocerebrosidase and parkinsonism: lessons to learn. AB - Both homo- (causing autosomal-recessive Gaucher's disease; GD) and heterozygous mutations in the glucocerebrosidase gene (GBA) are associated with Parkinson's disease (PD), and represent the most robust known genetic susceptibility factors identified in PD. Since the accumulation of alpha-synuclein has been considered critical to the pathogenesis of PD among several possible pathways through which glucocerebrosidase (GCase) deficiency may promote the pathogenesis of PD, particular attention was given to the reciprocity with alpha-synuclein levels, lysosomal dysfunction, endoplasmatic reticulum-Golgi trafficking of GCase, dysregulation of calcium homeostasis and mitochondrial abnormalities. The proportion of PD patients that carry GBA mutations is estimated to be approximately between 5 and 10 %. Individual PD patients with or without GBA mutations cannot be discriminated on clinical or pathological grounds. However, GBA mutation carriers may have slightly earlier age at PD onset, more likely have a positive family history for PD, and more prevalent non-motor symptoms when compared to those patients who are not carriers. Establishing the concept of GBA related PD promoted a search for the pathogenic mechanisms through which GCase deficiency may influence pathogenesis of PD, suggesting that targeting the GCase lysosomal pathway might be a rational approach for the development of neuroprotective drugs in PD. PMID- 26995358 TI - Detection of intrathecal immunoglobulin G synthesis by capillary isoelectric focusing immunoassay in oligoclonal band negative multiple sclerosis. AB - Oligoclonal immunoglobulin G bands (OCBs) restricted to the cerebrospinal fluid indicate intrathecal inflammation. Using isoelectric focusing and immunoblotting, they are detected in about 95 % of patients with clinically definite multiple sclerosis (MS). To elucidate whether in the remaining 5 % OCBs are truly absent or alternatively missed due to insufficient sensitivity of the routine measurement, we employed a new, highly sensitive nanoscale method for OCB detection. Capillary isoelectric focusing followed by immunological detection served to analyze OCBs in 33 well-characterized OCB-negative and 10 OCB-positive MS patients as well as in 100 OCB-negative control patients with non-inflammatory neurological diseases and 30 OCB-positive control patients with inflammatory neurological diseases. We detected intrathecal immunoglobulin G production in 10 out of 33 MS patients (30 %), initially diagnosed as being OCB-negative, and in all 10 OCB-positive MS patients, but in only 3 out of 100 non-inflammatory neurological controls (3 %) and in 29 of 30 inflammatory neurological controls (97 %). At least about one-third of MS patients without intrathecal immunoglobulin G synthesis according to standard methods are OCB-positive. Advanced methods for OCB detection may increase the analytical sensitivity for detecting OCB in patients with MS who are OCB-negative according to current routine methods. PMID- 26995360 TI - Internuclear ophthalmoplegia plus ataxia indicates a dorsomedial tegmental lesion at the pontomesencephalic junction. AB - Internuclear ophthalmoplegia (INO) indicates a lesion involving the medial longitudinal fasciculus (MLF) that interconnects the abducens nucleus and medial rectus subnucleus of the oculomotor nuclear complex. In fact, rostral-caudal localization value of the INO is often limited except when it accompanies symptoms and signs owing to involvement of nearby structures. Ataxia is often observed in lesions involving the cerebellum or the fibers to and from it anywhere in the brainstem. Herein, we sought to determine the localizing value of INO plus ataxia in the rostrocaudal axis of the brainstem. Thirty patients with INO plus limb or truncal ataxia were subjected to analyses. For comparison, 20 patients with isolated INO without any ataxia served as the control. We determined the lesion extent in the MRIs responsible for INO plus ataxia using a probabilistic lesion mapping and subtraction analysis and analyzed the neuro otologic findings using video-oculography. In patients with INO with limb or truncal ataxia, the responsible lesions were mostly restricted to the paramedian tegmentum at the pontomesencephalic junction. In contrast, the lesions causing isolated INO without ataxia were mostly located in the caudal or mid-pontine area. The rostro-caudal distribution of the lesions was similar among the patients with only limb ataxia (n = 3), both limb and truncal ataxia (n = 10), and only truncal ataxia (n = 17). INO plus ataxia indicates a lesion involving the MLF at the pontomesencephalic junction. Damage to the brachium conjunctivum or mesencephalic locomotor region may explain the ataxia in association with INO in lesions involving this area. PMID- 26995359 TI - Expanded phenotypic spectrum of the m.8344A>G "MERRF" mutation: data from the German mitoNET registry. AB - The m.8344A>G mutation in the MTTK gene, which encodes the mitochondrial transfer RNA for lysine, is traditionally associated with myoclonic epilepsy and ragged red fibres (MERRF), a multisystemic mitochondrial disease that is characterised by myoclonus, seizures, cerebellar ataxia, and mitochondrial myopathy with ragged red fibres. We studied the clinical and paraclinical phenotype of 34 patients with the m.8344A>G mutation, mainly derived from the nationwide mitoREGISTER, the multicentric registry of the German network for mitochondrial disorders (mitoNET). Mean age at symptom onset was 24.5 years +/-10.9 (6-48 years) with adult onset in 75 % of the patients. In our cohort, the canonical features seizures, myoclonus, cerebellar ataxia and ragged-red fibres that are traditionally associated with MERRF, occurred in only 61, 59, 70, and 63 % of the patients, respectively. In contrast, other features such as hearing impairment were even more frequently present (72 %). Other common features in our cohort were migraine (52 %), psychiatric disorders (54 %), respiratory dysfunction (45 %), gastrointestinal symptoms (38 %), dysarthria (36 %), and dysphagia (35 %). Brain MRI revealed cerebral and/or cerebellar atrophy in 43 % of our patients. There was no correlation between the heteroplasmy level in blood and age at onset or clinical phenotype. Our findings further broaden the clinical spectrum of the m.8344A>G mutation, document the large clinical variability between carriers of the same mutation, even within families and indicate an overlap of the phenotype with other mitochondrial DNA-associated syndromes. PMID- 26995361 TI - Effectiveness of illness management and recovery (IMR) in the Netherlands: a randomised clinical trial. AB - BACKGROUND: Illness Management and Recovery (IMR) is intended to provide a structured psychosocial programme that helps to manage the disabling effects of severe mental illnesses such as schizophrenia and bipolar disorders. It is curriculum based and aims to improve different aspects of illness management and recovery through interventions such as goal-setting, psycho-education, coping and social skills training. Its overall aim is to improve illness outcomes and support subjective and objective recovery. To date there have been four RCTs on IMR; as these yielded mixed results, further research is needed. Our hypotheses aim to test the interrelatedness assumed in Mueser's Conceptual Framework for IMR for the many aspects of illness management, illness management outcomes and recovery. METHODS/DESIGN: This randomised multi-centre, single-blinded clinical trial is intended to compare IMR with treatment as usual for 200 outpatient clients with a severe and persistent mental illness (SMI). We will investigate whether IMR leads to better illness management, fewer symptoms and fewer relapses, and also to better subjective and objective recovery. The primary outcome measure is the score on the client version of the Illness Management and Recovery Scale. Secondary outcome measures are the clinician version of the Illness Management and Recovery scale, measures of illness management, coping, symptoms, the number of relapses, and measures of recovery. Measurement will take place before randomisation, and 12 and 18 months after randomisation. DISCUSSION: Overall, our study has the following strengths: 1.) our use of an RCT design in a country where the earlier RCTs on IMR were not conducted; 2.) the fact that participants will consist not only of people with a diagnosis of schizophrenia, but also of those with various types of SMI; 3.) our inclusion of 200 participants; and 4.) the fact that we will explore the working mechanisms described in Mueser's Conceptual Framework for IMR. Finally, 5.) because the RCT will be conducted in everyday clinical practice, we believe that the generalisability of our results will be good. TRIAL REGISTRATION: The Netherlands National Trial Register (identifier: NTR 5033 ). Date registered: 13 January 2015. PMID- 26995362 TI - A Systematic Analysis of Treatment Effects on Depressive Symptom Severity by Level of Coercion. AB - Few studies examine the effect of interpersonal, regulatory or legal coercion on the treatment of depressive symptoms. This retrospective case-control study compared the recovery rates of 574 adults whose level of coercion was scored on a 0-3 scale from fully voluntary to severe coercion when admitted to the Menninger Clinic between 2009 and 2014. The change in Patient Health Questionnaire-9 (PHQ 9) scores (measuring depression severity) from admission to discharge served as the primary outcome measure. Level of coercion was not associated with a difference in rate of improvement in PHQ-9 score. Greater improvement in PHQ-9 scores was associated with (a) older age, (b) lack of a psychotic spectrum disorder diagnosis, (c) stronger working alliance with treatment team, and (d) less difficulty with emotional regulation [lower Difficulties in Emotion Regulation Scale (DERS) scores]. DERS scores were the most impactful factor. This study suggests that licensure boards can continue to mandate treatment despite concerns that coercion may decrease treatment effectiveness. PMID- 26995363 TI - Impact of institutional culture on rates of transfusions during cardiovascular procedures: The Michigan experience. AB - BACKGROUND: Red blood cell (RBC) transfusions have been associated with morbidity and mortality in both coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). As a mechanism for identifying determinants of RBC practice, we quantified the relationship between a center's PCI and CABG transfusion rate. METHODS: We identified all patients undergoing CABG (n = 16,568) or PCI (n = 94,634) at each of 33 centers from 2010 through 2012 in the state of Michigan and compared perioperative RBC transfusion rates for CABG and PCI at each center. Crude and adjusted transfusion rates were modeled separately. We adjusted for common preprocedural risk factors (12 for CABG and 23 for PCI) and reported Pearson correlation coefficients based on the crude and risk adjusted rates. RESULTS: As expected, RBC transfusion was more common after CABG (mean 46.5%) than PCI (mean 3.3%), with wide variation across centers for both (CABG min:max 26.5:71.3, PCI min:max 1.6:6.0). However, RBC transfusion rates were significantly correlated between CABG and PCI in both crude, 0.48 (P = .005), and adjusted, 0.53 (P = .001), analyses. These findings were consistent when restricting to nonemergent cases (radj = 0.44, P = .001). CONCLUSIONS: Red blood cell transfusion rates were significantly correlated between the CABG and PCI at individual hospitals in Michigan, independent of patient case mix. Future work should explore institutional practice patterns, philosophies, and guidelines for RBC transfusions. PMID- 26995364 TI - Clinical characteristics and outcomes after unplanned intraaortic balloon counterpulsation in the Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction trial. AB - BACKGROUND: Despite advances in primary percutaneous coronary intervention (pPCI) and regional systems of care, the development of cardiogenic shock is associated with poor clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). We sought to better characterize the baseline characteristics and clinical outcomes of patients who underwent crossover to intraaortic balloon counterpulsation (IABC) in the CRISP AMI trial. METHODS: Patients with anterior STEMI were randomized to IABC before pPCI or pPCI alone. Infarct size and 6-month clinical outcomes were evaluated in patients both in the pPCI-alone group who did undergo crossover to IABC and those who did not undergo crossover to IABC. RESULTS: Among 176 patients randomized to pPCI alone, 161 patients did not later receive IABC during the index hospitalization, and 15 patients (8.5%) underwent crossover and did receive unplanned IABC. Hypotension and/or cardiogenic shock precipitated crossover to IABC in 12 patients (80%). Patients who underwent crossover to IABC demonstrated lower systolic and diastolic blood pressures on admission. At 6 months, rates of death (26.7% vs 3.1%, P = .003), readmission for severe hypotension (53.3% vs 3.7%, P < .001), resuscitated cardiac arrest, and ventricular arrhythmia were higher in the group that did crossover to IABC. Crossover to IABC was not associated with increased infarct size. CONCLUSIONS: The most significant predictor of crossover to IABC in the setting of anterior STEMI was relative hypotension at the time of hospital admission, and crossover to IABC in CRISP AMI was associated with significantly worse clinical outcomes. PMID- 26995365 TI - The LIBERTY study: Design of a prospective, observational, multicenter trial to evaluate the acute and long-term clinical and economic outcomes of real-world endovascular device interventions in treating peripheral artery disease. AB - BACKGROUND: Most peripheral artery disease (PAD) clinical device trials are supported by commercial manufacturers and designed for regulatory device approval, with extensive inclusion/exclusion criteria to support homogeneous patient populations. High-risk patients with advanced disease, including critical limb ischemia (CLI), are often excluded leading to difficulty in translating trial results into real-world clinical practice. As a result, physicians have no direct guidance regarding the use of endovascular devices. There is a need for objectively assessed studies to evaluate clinical, functional, and economic outcomes in PAD patient populations. STUDY DESIGN: LIBERTY is a prospective, observational, multicenter study sponsored by Cardiovascular Systems Inc (St Paul, MN) to evaluate procedural and long-term clinical and economic outcomes of endovascular device interventions in patients with symptomatic lower extremity PAD. Approximately 1,200 patients will be enrolled and followed up to 5 years: 500 patients in the "Claudicant Rutherford 2-3" arm, 600 in the "CLI Rutherford 4 5" arm, and 100 in the "CLI Rutherford 6" arm. The study will use 4 core laboratories for independent analysis and will evaluate the following: procedural and lesion success, rates of major adverse events, duplex ultrasound interpretations, wound status, quality of life, 6-minute walk test, and economic analysis. The LIBERTY Patient Risk Score(s) will be developed as a clinical predictor of outcomes to provide guidance for interventions in this patient population. CONCLUSION: LIBERTY will investigate real-world PAD patients treated with endovascular revascularization with rigorous study guidelines and independent oversight of outcomes. This study will provide observational, all comer patient clinical data to guide future endovascular therapy. PMID- 26995366 TI - Association of standard clinical and laboratory variables with red blood cell distribution width. AB - BACKGROUND: Red blood cell distribution width (RDW) strongly predicts clinical outcomes among patients with coronary disease and heart failure. The factors underpinning this association are unknown. METHODS: In 6,447 individuals enrolled in the Measurement to Understand the Reclassification of Disease of Cabarrus/Kannapolis (MURDOCK) Study who had undergone coronary angiography between 2001 and 2007, we used Cox proportional hazards modeling to examine the adjusted association between RDW and death, and death or myocardial infarction (MI). Multiple linear regression using the R(2) model selection method was then used to identify clinical factors associated with variation in RDW. RESULTS: Median follow-up was 4.2 (interquartile range 2.3-5.9) years, and the median RDW was 13.5% (interquartile range 12.9%-14.3%, clinical laboratory reference range 11.5%-14.5%). Red blood cell distribution width was independently associated with death (adjusted hazard ratio 1.13 per 1% increase in RDW, 95% CI 1.09-1.17), and death or MI (adjusted hazard ratio 1.12, 95% CI 1.08-1.16). Twenty-seven clinical characteristics and laboratory measures were assessed in the multivariable linear regression model; a final model containing 18 variables explained only 21% of the variation in RDW. CONCLUSIONS: Although strongly associated with death and death or MI, only one-fifth of the variation in RDW was explained by routinely assessed clinical characteristics and laboratory measures. Understanding the latent factors that explain variation in RDW may provide insight into its strong association with risk and identify novel targets to mitigate that risk. PMID- 26995367 TI - Racial/ethnic differences in atrial fibrillation symptoms, treatment patterns, and outcomes: Insights from Outcomes Registry for Better Informed Treatment for Atrial Fibrillation Registry. AB - BACKGROUND: Significant racial/ethnic differences exist in the incidence of atrial fibrillation (AF). However, less is known about racial/ethnic differences in quality of life (QoL), treatment, and outcomes associated with AF. METHODS: Using data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we compared clinical characteristics, QoL, management strategies, and long-term outcomes associated with AF among various racial/ethnic groups. RESULTS: We analyzed 9,542 participants with AF (mean age 74 +/- 11 years, 43% women, 91% white, 5% black, 4% Hispanic) from 174 centers. Compared with AF patients identified as white race, patients identified as Hispanic ethnicity and those identified as black race were younger, were more often women, and had more cardiac and noncardiac comorbidities. Black patients were more symptomatic with worse QoL and were less likely to be treated with a rhythm control strategy than other racial/ethnic groups. There were no significant racial/ethnic differences in CHA2DS2-VASc stroke or ATRIA bleeding risk scores and rates of oral anticoagulation use were similar. However, racial and ethnic minority populations treated with warfarin spent a lower median time in therapeutic range of international normalized ratio (59% blacks vs 68% whites vs 62% Hispanics, P < .0001). There was no difference in long-term outcomes associated with AF between the 3 groups at a median follow-up of 2.1 years. CONCLUSION: Relative to white and Hispanic patients, black patients with AF had more symptoms, were less likely to receive rhythm control interventions, and had lower quality of warfarin management. Despite these differences, clinical events at 2 years were similar by race and ethnicity. PMID- 26995368 TI - Initiation of beta-blocker therapy and depression after acute myocardial infarction. AB - INTRODUCTION: Although beta-blockers reduce mortality after acute myocardial infarction (AMI), early reports linking beta-blocker use with subsequent depression have potentially limited their use in vulnerable patients. We sought to provide empirical evidence to support or refute this concern by examining the association between beta-blocker initiation and change in depressive symptoms in AMI patients. METHODS: Using data from 2 US multicenter, prospective registries of AMI patients, we examined 1-, 6-, and 12-month changes in depressive symptoms after the index hospitalization among patients who were beta-blocker-naive on admission. Depressive symptoms were assessed using the validated 8-item Patient Health Questionnaire (PHQ-8), which rates depressive symptoms from 0 to 24, with higher scores indicating more depressive symptoms. A propensity-matched repeated measures linear regression model was used to compare change in depressive symptoms among patients who were and were not initiated on a beta-blocker after AMI. RESULTS: Of 3,470 AMI patients who were beta-blocker-naive on admission, 3,190 (91.9%) were initiated on a beta-blocker and 280 (8.1%) were not. Baseline PHQ-8 scores were higher in patients not initiated on a beta-blocker (mean 5.78 +/- 5.45 vs 4.88 +/- 5.11, P = .005). PHQ-8 scores were progressively lower at 1, 6, and 12 months in both the beta-blocker (mean decrease at 12 months 1.16, P < .0001) and no-beta-blocker groups (mean decrease 1.71, P < .0001). After propensity matching 201 untreated patients with 567 treated patients, initiation of beta-blocker therapy was not associated with a difference in mean change in PHQ-8 scores at 1, 6, or 12 months after AMI (absolute mean difference with beta blocker initiation at 12 months of 0.08, 95% CI -0.81 to 0.96, P = .86). CONCLUSIONS: Initiation of beta-blocker therapy after AMI was not associated with an increase in depressive symptoms. Restricting beta-blocker use because of concerns about depression appears unwarranted and may lead to undertreatment of AMI patients. PMID- 26995369 TI - High-sensitive troponin T is associated with all-cause and cardiovascular mortality in stable outpatients with type 2 diabetes (ZODIAC-37). AB - BACKGROUND: We aimed to investigate whether high-sensitive cardiac troponin T (hs cTnT) is associated with all-cause and cardiovascular mortality in stable type 2 diabetes (T2D) outpatients treated in primary care. METHODS: Cardiac troponin T was measured with a high-sensitive assay at baseline in patients with T2D participating in the observational ZODIAC study. Cox proportional hazards models were used to investigate the relationship between hs-cTnT and mortality with adjustment for selected confounders. Risk prediction capabilities of hs-cTnT were assessed with Harrell C statistics. RESULTS: Complete baseline data were available for 1,133 patients. During median follow-up of 11 (7-14) years, 513 (45%) patients died, of which 218 (42%) died of cardiovascular causes. Of the patients with undetectable hs-cTnT levels (<3 ng/L), only 23% died, compared with 58% with low detectable levels (3-14 ng/L) and 84% with raised levels (>=14 ng/L). Natural log hs-cTnT was significantly associated with all-cause mortality (hazard ratio 1.30, 95% CI 1.19-1.42) and cardiovascular mortality (hazard ratio 1.33, 95% CI 1.15-1.53), independent of potential confounders. The Harrell C statistic for the crude model of hs-cTnT was 0.72 (95% CI 0.70-0.75) for all cause mortality and 0.74 (95% CI 0.71-0.77) for cardiovascular mortality. CONCLUSIONS: Higher levels of hs-cTnT are associated with mortality in stable outpatients with T2D. The high crude Harrell C values and the excellent prognosis of patients with undetectable levels illustrate the strength of hs-cTnT as a potential marker for mortality. PMID- 26995370 TI - Association between a healthy cardiovascular risk factor profile and coronary artery calcium score: Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). AB - BACKGROUND: Our goal was to evaluate cross-sectionally the association between ideal risk factor (IRF) profile and the presence and severity of subclinical atherosclerosis measured as coronary artery calcium (CAC) in the Brazilian Longitudinal Study of Adult Health. METHODS: We included 4,077 participants with no prior history of cardiovascular disease aged 35 to 74 years who underwent CAC measurement. The 2010 Task Force of the American Heart Association cutoffs were used to define the ideal level of smoking, physical activity, diet, blood pressure, glucose/cholesterol levels, and body mass index. RESULTS: Participants were categorized according the number of IRF: 0 to 1 (n = 1,025, 25.1%), 2 (n = 1,200, 29.4%), 3 to 4 (n = 1,551, 38.1%), or 5 to 7 (n = 301, 7.4%). Compared to individuals with 0 to 1 IRF, the odds ratio of participants with 2 IRFs presenting with CAC >0 (compared to 0), >=100 (compared to <100), and >=400 (compared to <400) was 0.75 (95% CI 0.62-0.91), 0.64 (0.49-0.84), and 0.75 (0.49 1.15), respectively. Similarly, the odds ratios of CACs >0, >=100, and >=400 in individuals with 3 to 4 IRFs were 0.59 (95% CI 0.48-0.71), 0.46 (0.34-0.62), and 0.50 (0.30-0.83), respectively, and, for individuals with 5 to 7 IRFs, were 0.36 (95% CI 0.24-0.56), 0.22 (0.09-0.55), and 0.20 (0.03-1.45), respectively. CONCLUSIONS: Subjects with an IRF profile have lower CAC when compared to subjects with fewer controlled risk factors. However, even among individuals with 5 to 7 IRFs, it is possible to find a CAC higher than zero reflecting that measures of IRF do not fully account for all factors that resulted in coronary artery disease. PMID- 26995371 TI - Pooled analysis of adverse event collection from 4 acute coronary syndrome trials. AB - BACKGROUND: Adverse event collection in randomized clinical trials establishes drug safety. Although costly and regulated, it is rarely studied. METHODS: Adverse event data from 4 clinical trials (APPRAISE-2, PLATO, TRACER, TRILOGY ACS) comprising 48,118 participants with acute coronary syndromes were pooled to compare patterns and determinants of reporting. Events were classified as serious (SAE) or nonserious (AE) from hospital discharge to 1 year; study end points were excluded. RESULTS: In total, 84,901 events were reported. Of those, 12,266 (14.4%) were SAEs and 72,635 (85.6%) were AEs. Of all participants, 7,823 (16.3%) had SAEs, 18,124 (37.7%) had only AEs, and 22,171 (46.1%) had neither. Nonserious adverse events were distributed across system organ classes: general disorders (11%), infection (10%), gastrointestinal (10%), respiratory (9%), cardiovascular (8.4%), and other (35%). Serious adverse events had a higher proportion of cardiovascular causes (14.0%). Event reporting was highest after hospital discharge, decreasing rapidly during the following 3 months. In a Cox proportional hazards model, chronic obstructive pulmonary disease (hazard ratio 1.58, 95% CI 1.44-1.74), heart failure (1.55, 1.40-1.70), older age, and female sex were independent predictors of more SAEs, whereas enrollment in Eastern Europe (0.63, 0.58-0.69) or Asia (0.84, 0.75-0.94) were independent predictors of fewer SAEs. CONCLUSIONS: Half of all participants reported adverse events in the year after acute coronary syndrome; most were AEs and occurred within 3 months. The high volume of events, as well as the variation in SAE reporting by characteristics and enrollment region, indicates that efforts to refine event collection in large trials are warranted. PMID- 26995373 TI - Noninvasive cardiac output estimation by inert gas rebreathing in pediatric and congenital heart disease. AB - BACKGROUND: Inert gas rebreathing (IGR) techniques provide rapid, reliable estimates of cardiac output in adults with structurally normal hearts. Data on IGR reliability in pediatric and congenital heart disease populations are lacking. Our objective was to validate pulmonary blood flow (Qp) measurement by IGR compared with clinical reference tests, cardiovascular magnetic resonance (CMR), and indirect Fick. METHODS: Pulmonary blood flow was measured by IGR and CMR or indirect Fick in 80 patients grouped by presence and type of shunt lesion. Inert gas rebreathing precision was assessed using Bland-Altman analysis, repeatability coefficient, intraclass correlation, and coefficient of error. Agreement with the reference tests was assessed with Bland-Altman plots. For comparison, agreement between the 2 reference tests, CMR and indirect Fick, was assessed in 34 contemporary patients. RESULTS: Subjects were aged 7-78 years and had a wide range of cardiac diagnoses. Inert gas rebreathing Qp showed good repeatability (95% limits of agreement for 2 trials = +/-22%, repeatability coefficient = 1.2 L/min, intraclass correlation = 0.92, and coefficient of error = 5%). In the absence of left-to-right shunting (n = 67), IGR Qp estimates agreed with CMR and indirect Fick Qp estimates, and the reference tests agreed with each other, with mean bias <=10% (<=0.5 L/min) and 95% limits of agreement +/-33%-38%. Conversely, IGR was unreliable in patients with left-to-right shunt (n = 14), with large bias (-58%, -4.0 L/min) and wide limits of agreement (+/-76%). CONCLUSIONS: Inert gas rebreathing reliably estimates Qp in children and adults with congenital heart disease in the absence of left-to-right shunting, with agreement comparable to that seen between CMR and indirect Fick estimates. PMID- 26995372 TI - Effect of Angiotensin II Type I Receptor Blockade with Valsartan on Carotid Artery Atherosclerosis: A Double Blind Randomized Clinical Trial Comparing Valsartan and Placebo (EFFERVESCENT). AB - BACKGROUND: Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis. METHODS: Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium dependent and -independent vascular function. RESULTS: Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, 0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [ 0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function. CONCLUSIONS: In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation. PMID- 26995374 TI - Rationale for the Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects Trial (POST5). AB - BACKGROUND: Vasovagal syncope (VVS) is a common problem associated with a poor quality of life, which improves when syncope frequency is reduced. Effective pharmacological therapies for VVS are lacking. Metoprolol is a beta-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (>=40 years) VVS patients. Given the limited therapeutic options, a placebo controlled clinical trial of metoprolol for the prevention of VVS in older patients is needed. STRUCTURE OF STUDY: The POST5 is a multicenter, international, randomized, placebo-controlled study of metoprolol in the prevention of VVS in patients >=40 years old. The primary endpoint is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive metoprolol 25 to 100 mg BID or matching placebo, and followed up for 1 year. Secondary end points include syncope frequency, presyncope, quality of life, and cost analysis. Primary analysis will be intention to treat, with a secondary on treatment analysis. POWER CALCULATIONS: A sample size of 222, split equally between the groups achieves 85% power to detect a hazard rate of 0.3561 when the event rates are 50% and 30% in the placebo and metoprolol arms. Allowing for 10% dropout, we propose to enroll 248 patients. IMPLICATIONS: This study will be the first adequately powered trial to determine whether metoprolol is effective in preventing VVS in patients >=40 years. If effective, metoprolol may become the first line pharmacological therapy for these patients. PMID- 26995375 TI - Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial. AB - BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin. METHODS AND RESULTS: In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. CONCLUSIONS: The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome. PMID- 26995377 TI - The atrial fibrillation conundrum in dialysis patients. AB - The burden of atrial fibrillation (AF) and the risk of stroke are high in dialysis patients. The decision to use anticoagulation rests heavily on effective risk stratification. Because both the pathophysiology of the disease and the response to therapy differ in dialysis, data from the general population cannot be extrapolated. The effect of vitamin K antagonists (VKAs) on the risk of stroke in dialysis patients with AF has not been studied in randomized trials. The available observational data provide contradictory results, reflecting differences in the degree of residual confounding, quality of international normalized ratio control, and stroke characterization. Dialysis patients have a high baseline bleeding risk. It remains unclear to what extent VKAs affect the overall bleeding propensity, but they may significantly increase the risk of intracerebral hemorrhage. Vascular calcifications are extremely prevalent in dialysis patients and independently associated with an adverse outcome. Vitamin K antagonists inhibit the activity of key anticalcifying proteins and may thus compound the risk of vascular calcification progression in dialysis. In the absence of evidence-based guidelines for anticoagulation in dialysis patients with AF, we provide recommendations to assist clinicians in individualized risk stratification. We further propose that new oral anticoagulants may have a better benefit-risk profile in dialysis patients than VKA, provided appropriate dose reductions are made. New oral anticoagulant may yield more on-target anticoagulation, reduce the risk of intracerebral bleeding, and not interfere with vascular calcification biology. Clinical trials with new oral anticoagulant in dialysis patients are eagerly awaited, to reveal whether these assumptions can be confirmed. PMID- 26995376 TI - Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. AB - Exenatide once-weekly is an extended release formulation of exenatide, a glucagon like peptide-1 receptor agonist, which can improve glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usual care with usual care alone on major cardiovascular outcomes. EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35 countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years. Participants will be randomized (1:1) to receive exenatide once-weekly 2 mg or matching placebo by subcutaneous injections. The trial will continue until 1,360 confirmed primary composite cardiovascular end points, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, have occurred. The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary composite cardiovascular end point. EXSCEL is powered to detect a 15% relative risk reduction in the exenatide once-weekly group, with 85% power and a 2-sided 5% alpha. The primary safety hypothesis is that exenatide once-weekly is noninferior to usual care with respect to the primary cardiovascular composite end point. Noninferiority will be concluded if the upper limit of the CI is <1.30. EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broad range of cardiovascular risk. It will also provide long-term safety information on exenatide once-weekly in people with T2DM. ClinicalTrials.gov Identifier: NCT01144338. PMID- 26995378 TI - A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: The design of the GEMINI-ACS-1 phase II study. AB - Dual antiplatelet therapy (DAPT), the combination of aspirin and a P2Y12 inhibitor, given for 12 months remains the standard of care after presentation with acute coronary syndrome (ACS) because it has been shown to be associated with a significant reduction in ischemic events compared with aspirin monotherapy. The factor Xa inhibitor rivaroxaban was shown to be associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, and stroke, and resulted in a nominal reduction in cardiovascular death, when added to background DAPT in the ATLAS ACS 2-TIMI 51 trial; however, there was excessive bleeding with this "triple-therapy" approach. The combination of rivaroxaban with P2Y12 inhibition in a "dual-pathway" approach may be an effective therapeutic regimen for the treatment of ACS, given the known importance of P2Y12 inhibition after stenting and intriguing data that the combination of an anticoagulant with clopidogrel after stenting in patients with atrial fibrillation appears an attractive option to this patient population. GEMINI-ACS-1 is a prospective, randomized, double-dummy, double-blind, active controlled trial that will assess the safety of dual antithrombotic therapy (rivaroxaban [2.5 mg twice daily] + P2Y12 inhibitor) as compared with DAPT (aspirin [100 mg] + P2Y12 inhibitor) within 10 days of an ACS event in 3,000 patients. Patients will be randomized in a 1:1 ratio stratified by intended P2Y12 inhibitor use (clopidogrel 75 mg daily or ticagrelor 90 mg twice daily), with 1500 patients expected in each P2Y12 inhibitor strata. The primary end point is Thrombolysis in Myocardial Infarction clinically significant bleeding (major, minor, or requiring medical attention). The exploratory efficacy determination will be a composite of cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis. GEMINI-ACS-1 will assess the safety and feasibility of dual antithrombotic therapy with rivaroxaban and a P2Y12 inhibitor compared with conventional DAPT for the treatment for patients with recent ACS. PMID- 26995379 TI - Rationale and methodology of a collaborative learning project in congenital cardiac care. AB - BACKGROUND: Collaborative learning is a technique through which individuals or teams learn together by capitalizing on one another's knowledge, skills, resources, experience, and ideas. Clinicians providing congenital cardiac care may benefit from collaborative learning given the complexity of the patient population and team approach to patient care. RATIONALE AND DEVELOPMENT: Industrial system engineers first performed broad-based time-motion and process analyses of congenital cardiac care programs at 5 Pediatric Heart Network core centers. Rotating multidisciplinary team site visits to each center were completed to facilitate deep learning and information exchange. Through monthly conference calls and an in-person meeting, we determined that duration of mechanical ventilation following infant cardiac surgery was one key variation that could impact a number of clinical outcomes. This was underscored by one participating center's practice of early extubation in the majority of its patients. A consensus clinical practice guideline using collaborative learning was developed and implemented by multidisciplinary teams from the same 5 centers. The 1-year prospective initiative was completed in May 2015, and data analysis is under way. CONCLUSION: Collaborative learning that uses multidisciplinary team site visits and information sharing allows for rapid structured fact-finding and dissemination of expertise among institutions. System modeling and machine learning approaches objectively identify and prioritize focused areas for guideline development. The collaborative learning framework can potentially be applied to other components of congenital cardiac care and provide a complement to randomized clinical trials as a method to rapidly inform and improve the care of children with congenital heart disease. PMID- 26995380 TI - Cardiovascular outcomes after pharmacologic stress myocardial perfusion imaging. AB - BACKGROUND: While pharmacologic stress single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is used for noninvasive evaluation of patients who are unable to perform treadmill exercise, its impact on net reclassification improvement (NRI) of prognosis is unknown. METHODS: We evaluated the prognostic value of pharmacologic stress MPI for prediction of cardiovascular death or non-fatal myocardial infarction (MI) within 1 year at a single-center, university-based laboratory. We examined continuous and categorical NRI of pharmacologic SPECT-MPI for prediction of outcomes beyond clinical factors alone. RESULTS: Six thousand two hundred forty patients (median age 66 years [IQR 56 74], 3466 men) were studied and followed for 5963 person-years. SPECT-MPI variables associated with increased risk of cardiovascular death or non-fatal MI included summed stress score, stress ST-shift, and post-stress resting left ventricular ejection fraction <=50%. Compared to a clinical model which included age, sex, cardiovascular disease, risk factors, and medications, model chi(2) (210.5 vs. 281.9, P < .001) and c-statistic (0.74 vs. 0.78, P < .001) were significantly increased by addition of SPECT-MPI predictors (summed stress score, stress ST-shift and stress resting left ventricular ejection fraction). SPECT-MPI predictors increased continuous NRI by 49.4% (P < .001), reclassifying 66.5% of patients as lower risk and 32.8% as higher risk of cardiovascular death or non fatal MI. Addition of MPI predictors to clinical factors using risk categories, defined as <1%, 1% to 3%, and >3% annualized risk of cardiovascular death or non fatal MI, yielded a 15.0% improvement in NRI (95% CI 7.6%-27.6%, P < .001). CONCLUSIONS: Pharmacologic stress MPI substantially improved net reclassification of cardiovascular death or MI risk beyond that afforded by clinical factors. PMID- 26995381 TI - Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial. AB - Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients. PMID- 26995382 TI - Toward evidence-based health care delivery reform. PMID- 26995384 TI - Cardiopulmonary exercise testing in heart failure preserved ejection fraction: Time to expand the paradigm in the prognostic algorithm. PMID- 26995383 TI - Dual health care system use is associated with higher rates of hospitalization and hospital readmission among veterans with heart failure. AB - BACKGROUND: Heart failure (HF) frequently causes hospital admission and readmission. Patients receiving care from multiple providers and facilities (dual users) may risk higher health care utilization and worse health outcomes. METHODS: To determine rates of emergency department (ED) visits, hospitalizations, and hospital readmissions relative to dual use among HF patients, we analyzed a retrospective cohort of 13,977 veterans with HF hospitalized at the Veterans Affairs (VA) or non-VA facilities from 2007 to 2011; we analyzed rates of acute health care utilization using zero-inflated negative binomial regression. RESULTS: Compared to VA-only users and dual users, individuals receiving all of their ED and hospital care outside the VA tended to be older, more likely to be non-Hispanic white and married, and less likely to have high levels of service connected disability. Compared to VA-only users, dual users had significantly higher rates of ED visits for HF as a primary diagnosis (adjusted rate ratio 1.15, 95% CI 1.04-1.27), hospitalization for HF (adjusted rate ratio 1.4, 95% CI 1.26-1.56), hospital readmission after HF hospitalization (all cause) (1.46, 95% CI 1.30-1.65), and HF-specific hospital readmission after HF hospitalization (1.46, 95% CI 1.31-1.63). With the exception of hospitalization for any primary diagnosis, non-VA-only users had significantly lower rates of ED visits, hospitalization, and readmission compared to VA-only users. CONCLUSIONS: Dual use is associated with higher rates of health care utilization among patients with HF. Interventions should be devised to encourage continuity of care where possible and to improve the effectiveness and safety of dual use in instances where it is necessary or desired. PMID- 26995385 TI - Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project. AB - BACKGROUND: Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. METHODS: This was a retrospective analysis of patients with HFpEF (ejection fraction >= 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. RESULTS: We identified 173 HFpEF patients (45% women, 58% non white, age 54 +/- 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and beta blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald chi(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald chi(2) = 11.8, P = .001). VE/VCO2 slope (Wald chi(2)= 0.4, P = .54) and EOV (Wald chi(2) = 0.15, P = .70) had no significant association to the composite outcome. CONCLUSION: These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients. PMID- 26995386 TI - Prosthetic valve thrombosis: When prevention is better than treatment. PMID- 26995387 TI - Multimodality approach to diagnosis of prosthetic valve thrombosis. PMID- 26995388 TI - Patient participation in contemporary health care: promoting a versatile patient role. PMID- 26995389 TI - Distinctive pattern of expression of spermatogenic molecular markers in testes of azoospermic men with non-mosaic Klinefelter syndrome. AB - PURPOSE: Mature sperm cells can be found in testicular specimens extracted from azoospermic men with non-mosaic Klinefelter syndrome (KS). The present study evaluates the expression of various known molecular markers of spermatogenesis in a population of men with KS and assesses the ability of those markers to predict spermatogenesis. METHODS: Two groups of men with non-obstructive azoospermia who underwent testicular sperm-retrieval procedures were included in the study: 31 had non-mosaic KS (KS group) and 91 had normal karyotype (NK group). Each group was subdivided into mixed atrophy (containing some mature sperm cells) or Sertoli cell only syndrome according to testicular histology and cytology observations. Semi-quantitative histological morphometric analysis (interstitial hyperplasia and hyalinization, tubules with cells and abnormal thickness of the basement membrane) and expression of spermatogenetic markers (DAZ, RBM, BOLL, and CDY1) were evaluated and compared among those subgroups. RESULTS: Clear differences in the histological morphometry and spermatogenetic marker expression were noted between the KS and NK groups. There was a significant difference in the expression of spermatogenetic markers between the subgroups of the NK group (as expected), while no difference could be discerned between the two subgroups in the KS group. CONCLUSION: We conclude that molecular spermatogenetic markers have a pattern of expression in men with KS that is distinctively different from that of men with NK, and that it precludes and limits their use for predicting spermatogenesis in the former. It is suggested that this difference might be due to the specific highly abnormal histological morphometric parameters in KS specimens. PMID- 26995390 TI - Providing rapid feedback to residents on their teaching skills: an educational strategy for contemporary trainees. AB - OBJECTIVE: The objective of this study was to assess the attitudes of contemporary residents toward receiving rapid feedback on their teaching skills from their medical student learners. METHODS: Participants consisted of 20 residents in their second post-graduate training year. These residents facilitated 44 teaching sessions with medical students within our Resident-as Teacher program. Structured, written feedback from students was returned to the resident within 3 days following each session. Residents completed a short survey about the utility of the feedback, whether they would make a change to future teaching sessions based on the feedback, and what specifically they might change. The survey utilized a 4-point scale ("Not helpful/likely=1" to "Very helpful/likely=4"), and allowed for one free-text response. Free-text responses were hand-coded and underwent qualitative analysis to identify themes. RESULTS: There were 182 student feedback encounters resulting from 44 teaching sessions. The survey response rate was 73% (32/44). Ninety-four percent of residents rated the rapid feedback as "very helpful," and 91% would "very likely" make a change to subsequent sessions based on student feedback. Residents' proposed changes included modifications to session content and/or their personal teaching style. CONCLUSIONS: Residents found that rapid feedback received from medical student learners was highly valuable to them in their roles as teachers. A rapid feedback strategy may facilitate an optimal educational environment for contemporary trainees. PMID- 26995391 TI - Differential expression and clinical relevance of MUC1 in renal cell carcinoma metastasis. AB - PURPOSE: To determine the differential expression patterns and prognostic relevance of Mucin-1 (MUC1) expression in clear cell renal cell carcinoma (RCC) metastasis. METHODS: Tissue microarrays (TMA) from samples of 151 RCC metastases, 61 primary RCCs and corresponding benign renal tissues were immunohistochemically stained for MUC1 and semi-quantitatively evaluated by immunoreactivity scores (IRS). MUC1 differential expression in metastasis, primary RCC and normal tissue were comparatively analyzed. Patient characteristics and clinical follow-up for patients with metastatic RCC (mRCC) were recorded. Correlations of MUC1 expression with mRCC survival were determined. RESULTS: Median cytoplasmic expression was highest in benign tissue (IRS = 1.04). Primary RCC (0.50) and metastasis (0.12) showed significantly lower cytoplasmic staining intensity. Membranous expression in benign tissue was, however, significantly lower (0.21) compared with primary RCC (0.59) and metastasis (0.57). Notable differences of MUC1 cytoplasmic and membranous expression were observed between different metastasis sites. Significantly higher (P = 0.014) membranous expression was observed in pulmonary versus non-pulmonary lesions, while no significant differences of cytoplasmic MUC1 expression were observed. The prognostic relevance of MUC1 expression in metastatic RCC was limited. CONCLUSIONS: MUC1 is differentially expressed in benign renal tissue, primary RCC and RCC metastasis. Membranous MUC1 expression was significantly elevated in pulmonary metastases compared to non-pulmonary lesions, which may reflect individual biology and putative response to MUC1-based anti-cancer therapy. PMID- 26995393 TI - Visually significant cataract: a global challenge. PMID- 26995394 TI - Water drinking test: new applications. PMID- 26995392 TI - Microvascular Complications and Prevalence of Nocturia in Japanese Patients With Type 2 Diabetes Mellitus: The Dogo Study. AB - OBJECTIVE: To evaluate the association between microvascular complications and nocturia among Japanese patients with type 2 diabetes mellitus. METHODS: Study subjects were 731 Japanese patients with type 2 diabetes mellitus. A self administered questionnaire was used to collect information on the variables under study. Study subjects were considered to have nocturia if they answered "once or more" to the question: "How many times do you typically wake up to urinate from sleeping at night until waking in the morning?" Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, the absence of the Achilles reflex, or abnormal vibration perception. Diabetic nephropathy was defined as positive when the estimated glomerular filtration rate was <30 mL/min/1.73 m(2) and/or the urine albumin-to creatinine ratio was >=34 mg/mmol creatinine. Several ophthalmology specialists were responsible for evaluating diabetic retinopathy. Adjustment was made for sex, age, body mass index, duration of diabetes mellitus, current smoking, current drinking, hypertension, stroke, ischemic heart disease, and glycated hemoglobin. RESULTS: The prevalence of nocturia was 80.4%. Diabetic retinopathy was independently positively associated with nocturia (adjusted odds ratio 2.39 [95% confidence interval: 1.08-6.11]). In contrast, diabetic nephropathy or diabetic neuropathy was not associated with nocturia. CONCLUSION: In Japanese patients with type 2 diabetes mellitus, only diabetic retinopathy was independently positively associated with nocturia. PMID- 26995396 TI - Genetic diversity and population structure of Brassica oleracea germplasm in Ireland using SSR markers. AB - The most economically important Brassica oleracea species is endangered in Ireland, with no prior reported genetic characterization studies. This study assesses the genetic diversity, population structure and relationships of B. oleracea germplasm in Ireland using microsatellite (SSRs) markers. A total of 118 individuals from 25 accessions of Irish B. oleracea were genotyped. The SSR loci used revealed a total of 47 alleles. The observed heterozygosity (0.699) was higher than the expected one (0.417). Moreover, the average values of fixation indices (F) were negative, indicating excess of heterozygotes in all accessions. Polymorphic information content (PIC) values of SSR loci ranged from 0.27 to 0.66, with an average of 0.571, and classified 10 loci as informative markers (PIC>0.5) to differentiate among the accessions studied. The genetic differentiation among accessions showed that 27.1% of the total genetic variation was found among accessions, and 72.9% of the variation resided within accessions. The averages of total heterozygosity (H(T)) and intra-accession genetic diversity (H(S)) were 0.577 and 0.442, respectively. Cluster analysis of SSR data distinguished among kale and Brussels sprouts cultivars. This study provided a new insight into the exploitation of the genetically diverse spring cabbages accessions, revealing a high genetic variation, as potential resources for future breeding programs. SSR loci were effective for differentiation among the accessions studied. PMID- 26995399 TI - Fine Substituent Effects in Sandwich Complexes: A Threshold Ionization Study of Monosubstituted Chromium Bisarene Compounds. AB - Mass-analyzed threshold ionization spectra of jet-cooled [(eta(6) -PhMe)(eta(6) PhH)Cr] and [(eta(6) -Ph2 )(eta(6) -PhH)Cr] reveal with unprecedented accuracy the effects of methyl and phenyl groups on the electronic structure of bis(eta(6) -benzene)chromium. These "pure" substituent effects allow quantitative experimental determination of the ionization energy changes caused by the mutual substituent influence in bisarene systems. Two types of such influence have been revealed for the first time in bis(eta(6) -toluene)chromium. PMID- 26995397 TI - Scorpions from the Mitaraka Massif in French Guiana: Description of one new genus and species (Scorpiones: Chactidae). AB - A new genus and species, Spinochactas mitaraka gen. n., sp. n. (Chactidae) are described from the Mitaraka Massif in French Guiana, a site located near the borders of French Guiana, Brazil, and Suriname. The description of the new genus and species brings further evidence of the biogeographic pattern of distribution presented by some elements of the family Chactidae endemic to the Tepuys or to the Inselberg formations of South America. PMID- 26995400 TI - [Minimally invasive radical prostatectomy: Contribution of robotic support, functional and oncological outcomes]. AB - OBJECTIVES: Radical prostatectomy (RP) remains a standard for localized prostate cancer treatment. The objective of this study is to present this operating technique of the robot-assisted radical prostatectomy (PR-RA) and to evaluate oncological and functional results as well as on the surgical safety. METHODS: A first series of 1679 patients consecutively operated in our institution with this technique from 2005 to 2010 and with a 5-year follow-up evaluated in 2014. The oncology monitoring is ensured with a PSA test every six months during the first three years and once a year the years after if the level remains undetectable. RESULTS: The oncologic outcomes show 17.4% for pT2 stages and 36.9% for pT3 stages positive margins. The level of biological recurrence is 21.27% with an average delay of 88 months as the time needed for the recurrence to occur. At 12 months, urinary continence (0-1pad/day) returned at 94% of all patients and potency with successful penetration for all men is 61.1% and 88.8% for men with sexual activity before surgery. CONCLUSIONS: The technique PRRA seems to be a reliable technique whose functional results studied from meta-analysis seem to be superior in terms of rapidity of recovery of the continence and erection in comparison with classical surgical or laparoscopic approach. PMID- 26995401 TI - [2016 news in oncologic surgery]. PMID- 26995402 TI - Oxidative instability of hemoglobin E (beta26 Glu->Lys) is increased in the presence of free alpha subunits and reversed by alpha-hemoglobin stabilizing protein (AHSP): Relevance to HbE/beta-thalassemia. AB - When adding peroxide (H2O2), beta subunits of hemoglobin (Hb) bear the burden of oxidative changes due in part to the direct oxidation of its Cys93. The presence of unpaired alpha subunits within red cells and/or co-inheritance of another beta subunit mutant, HbE (beta26 Glu->Lys) have been implicated in the pathogenesis and severity of beta thalassemia. We have found that although both HbA and HbE autoxidize at initially comparable rates, HbE loses heme at a rate almost 2 fold higher than HbA due to unfolding of the protein. Using mass spectrometry and the spin trap, DMPO, we were able to quantify irreversible oxidization of betaCys93 to reflect oxidative instability of beta subunits. In the presence of free alpha subunits and H2O2, both HbA and HbE showed betaCys93 oxidation which increased with higher H2O2 concentrations. In the presence of Alpha-hemoglobin stabilizing protein (AHSP), which stabilizes the alpha-subunit in a redox inactive hexacoordinate conformation (thus unable to undergo the redox ferric/ferryl transition), Cys93 oxidation was substantially reduced in both proteins. These experiments establish two important features that may have relevance to the mechanistic understanding of these two inherited hemoglobinopathies, i.e. HbE/beta thalassemia: First, a persistent ferryl/ferryl radical in HbE is more damaging to its own beta subunit (i.e., betaCys93) than HbA. Secondly, in the presence of excess free alpha-subunit and under the same oxidative conditions, these events are substantially increased for HbE compared to HbA, and may therefore create an oxidative milieu affecting the already unstable HbE. PMID- 26995403 TI - Coronary CT Angiography as a Diagnostic and Prognostic Tool: Perspective from a Multicenter Randomized Controlled Trial: PROMISE. AB - The PROMISE (Prospective multicenter imaging study for evaluation of chest pain) trial compared the effectiveness of coronary CT angiography and functional testing as initial diagnostic test for patients with suspicion for stable coronary artery disease (CAD). With 10,003 patients randomized at 193 sites, the PROMISE trial provides a snapshot of real-world care for this very common presentation. Over a median follow-up of 25 months, PROMISE did not find significant differences in major clinical events (composite endpoint 164 vs. 151, HR 1.04 (0.83-1.29); p = 0.75) between the two strategies. Other major findings were the large discrepancy between estimates of pre-test likelihood and observed prevalence for obstructive CAD (>=50 %) and the proportion of noninvasive tests positive for ischemia or obstructive CAD (53 vs. 11 %; respectively) and the better efficiency of coronary computed tomography angiography (CTA) to select patients for invasive coronary angiography (ICA) who had obstructive CAD (72 vs. 48 % for coronary CTA and functional testing, respectively). Radiation exposure was higher in the CT arm compared to all functional testing but lower than for nuclear perfusion stress testing. Improvement of patient selection for diagnostic testing and risk stratification will be keys to increase efficacy and efficiency of management of patients with suspicion for stable CAD. PMID- 26995405 TI - Mechanisms of metabolism, aging and obesity. PMID- 26995404 TI - Transient Constrictive Pericarditis: Current Diagnostic and Therapeutic Strategies. AB - Transient constrictive pericarditis is increasingly recognized as a distinct sub type of constrictive pericarditis. The underlying pathophysiology typically relates to impaired pericardial distensibility, associated with acute or sub acute inflammation, rather than the fibrosis or calcification often seen in chronic pericardial constriction. Accordingly, patients may present clinically with concomitant features of pericarditis and constrictive physiology. Non invasive multimodality imaging is advocated for diagnosis of transient constrictive pericarditis. Echocardiography remains the mainstay for initial evaluation of the dynamic features of constriction. However, cardiac magnetic resonance imaging can provide complimentary functional information, with the addition of dedicated sequences to assess for active pericardial edema and inflammation. Although transient pericardial constriction can spontaneously resolve, institution of anti-inflammatory therapy may hasten resolution or even prevent progression to chronic pericardial constriction. Non-steroidal anti inflammatory agents remain the initial treatment of choice, with subsequent consideration of colchicine, steroids, and other immune-modulating agents in more refractory cases. PMID- 26995406 TI - Neuronal Nitric Oxide Synthase Negatively Regulates Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration. AB - The study aimed to investigate the role of NO and neuronal NO synthase (nNOS) in Zn-induced neurodegeneration. Animals were treated with zinc sulfate (20 mg/kg), twice a week, for 2-12 weeks along with control. In a few sets, animals were also treated with/without a NO donor, sodium nitroprusside (SNP), or S-nitroso-N acetyl penicillamine (SNAP) for 12 weeks. Moreover, human neuroblastoma (SH-SY 5Y) cells were also employed to investigate the role of nNOS in Zn-induced toxicity in in vitro in the presence/absence of nNOS inhibitor, 7-nitroindazole (7-NI). Zn caused time-dependent reduction in nitrite content and total/nNOS activity/expression. SNP/SNAP discernibly alleviated Zn-induced neurobehavioral impairments, dopaminergic neurodegeneration, tyrosine hydroxylase (TH) expression, and striatal dopamine depletion. NO donors also salvage from Zn induced increase in lipid peroxidation (LPO), mitochondrial cytochrome c release, and caspase-3 activation. While Zn elevated LPO content, it attenuated nitrite content, nNOS activity, and glutathione level along with the expression of TH and nNOS in SH-SY-5Y cells. 7-NI further augmented Zn-induced changes in the cell viability, oxidative stress, and expression of TH and nNOS. The results obtained thus demonstrate that Zn inhibits nNOS that partially contributes to an increase in oxidative stress, which subsequently leads to the nigrostriatal dopaminergic neurodegeneration. PMID- 26995408 TI - The Musical Intellect of Infantile Nystagmus. PMID- 26995407 TI - Therapeutic Hypothermia Enhances Cold-Inducible RNA-Binding Protein Expression and Inhibits Mitochondrial Apoptosis in a Rat Model of Cardiac Arrest. AB - Therapeutic hypothermia is well known for its protective effect against brain injury after cardiac arrest, but the exact mechanism remains unclear. Cold inducible RNA-binding protein (CIRP), a member of cold shock protein, enables mammalian cells to withstand decreased temperature by regulating gene translation. However, the role of CIRP in global cerebral ischemia after therapeutic hypothermia has not been clearly elucidated. In the present study, rats resuscitated from 4 min of cardiac arrest were separately treated with therapeutic hypothermia (immediately after return of spontaneous circulation (ROSC); targeted temperature at 33 degrees C) and therapeutic normothermia (targeted temperature at 36.8 degrees C) for 6 h. The hippocampus was harvested at 0 h (baseline), 6 h, 12 h, 1 day, 3 days, and 7 days after ROSC. The expression of CIRP messenger RNA (mRNA) was assessed by real-time PCR. CIRP and mitochondrial apoptosis-associated proteins were tested by Western blot. The histological changes and neurological function were respectively evaluated by hematoxylin-eosin staining and neurological deficit score (NDS). Compared with baseline, rats resuscitated from cardiac arrest showed increased expression of CIRP, Bax, Caspase 9, and Caspase 3 and decreased expression of Bcl-2 in hippocampus (P < 0.05). However, therapeutic hypothermia after ROSC alleviated the alterations of Bax, Caspase 9, Caspase 3, and Bcl-2, while further increased the hippocampal expression of CIRP mRNA and protein, when compared with the normothermia rats (P < 0.05). In addition, compared with the therapeutic normothermia rats, histopathological damage in CA1 zone and NDS were respectively decreased and increased in the hypothermia rats (P < 0.05). Our findings suggest that 32 degrees C therapeutic hypothermia exerts an important neuroprotective effects by up-regulating CIRP expression and inhibiting mitochondrial apoptosis factor production in the cardiac arrest rat model. PMID- 26995409 TI - Effect of Serial Intrasilicone Oil Bevacizumab Injections in Eyes With Recurrent Proliferative Vitreoretinopathy Retinal Detachment. PMID- 26995410 TI - Are medical breakthroughs declining - The importance of case reports? AB - Case reports are a valuable though oft-underestimated source of clinical knowledge, even wisdom. They are extremely valuable to clinicians faced with new diseases, new investigations, and new therapies, where they provide the initial information, which serves as a basis to plan a detailed comparative study to provide definitive answers. The publication of cases and images-related reports is undoubtedly a gain for all, including medical students, medical teachers, the scientific community, medical professionals, healthcare managers, and patients. PMID- 26995411 TI - Pacemaker lead Candida endocarditis: Is medical treatment possible? PMID- 26995412 TI - Complex regional pain syndrome type I following pacemaker implantation. AB - A 70-year-old woman presented with burning pain and swelling over dorsum of right hand and small joints of the fingers, associated with redness, feeling of warmth, and stiffness of the fingers, with inability to bend the fingers since 2 months. The symptoms were progressively increasing in intensity for the past 1 month. There was no history of fever or trauma to the hand. Two months before her symptoms started, she had permanent pacemaker implanted for complete heart block with syncope. She was hypertensive and was on regular medication. Her X-ray of right hand showed decreased bone density (demineralisation), suggestive of osteopenia. A diagnosis of reflex sympathetic dystrophy syndrome or complex regional pain syndrome type I induced by pacemaker insertion was made. She was treated with amitriptyline and steroids, after which her symptoms improved dramatically. PMID- 26995413 TI - CT imaging of post-myocardial infarction ventricular septal defect with a contained rupture/pseudoaneurysm. AB - This is a CT imaging study of a 63-year-old female who presented to our center with ST segment elevation MI and was found to have life threatening post-MI ventricular septal defect with associated pseudoaneurysm, which was detected on cardiac CTA. The patient refused surgical management and had a successful percutaneous VSD repair. PMID- 26995415 TI - Bioresorbable vascular scaffolds for LMCA with double vessel disease under IVUS guidance. AB - An 80-year-old male patient, presented with chest pain. ECG showed ST elevation in leads V2 to V4 and T wave inversion in leads V2-V6. Check angiogram revealed ostial LMCA 70% lesion & mid-LAD 90% lesion and LCX proximal 80% lesion. Predilatation of LMCA lesion was done with 2.0 * 12 mm NC Trek balloon and the LAD lesion with 2.0 * 12 mm and 2.5 * 08 mm (NC Trek balloons). Prestenting IVUS (Intravascular ultrasound) was done with Atlantis SR pro 40 MHz 3.6 Fr catheter. IVUS showed the LAD to have a minimal lumen area of 2.6 sq mm with 90% fibrotic plaque and a vessel size of 2.5mm and the LMCA to have a minimal lumen area of 8.8 sq mm with 70% fibrotic plaque and vessel size of 3.8mm. Mid-LAD stenting was done with 2.5 * 28 mm Absorb Stent (BVS). Predilatation of LCX lesion was done with 2.5 * 08 mm NC Trek balloon. Then stenting was performed with 3.0 * 28 mm Absorb Stent (BVS). Check angiogram showed edge dissection proximal to the BVS Stent which was covered with 3.0 * 12 mm Xience Xpedtion Stent (DES). Then LMCA Stenting was done with 3.5 * 12 mm Absorb Stent. Post dilatation was done with 4.0 * 08 mm NC Trek balloon. Post Stenting LMCA - LAD IVUS was done. LMCA and LAD Stents were well opposed without any dissection or residual stenosis. TIMI III Flow was achieved in the final results. PMID- 26995414 TI - Absent right coronary artery: A case of single coronary artery or congenital ostial atresia? AB - Atresia of the right coronary artery ostium is a rare anatomic variant of the coronary circulation. It is often difficult to differentiate from single coronary artery. Its presence unassociated with any other anomaly has never been described in an adult individual. We report this unusual anomaly and discuss its anatomical and pathophysiological significance and possible ways to differentiate from single coronary artery. PMID- 26995416 TI - Double loop technique for Percutaneous Transvenous Mitral Commissurotomy. AB - Percutaneous Transvenous Mitral Commissurotomy (PTMC) is a standard treatment for critical mitral stenosis. In certain situations such as large left atrium (LA) or low trans-septal puncture, there is technical difficulty in crossing a PTMC balloon across the mitral valve, leading to high failure rate. I hereby describe a case of PTMC successfully performed by using double loop technique to cross the mitral valve. PMID- 26995417 TI - Percutaneous tricuspid valvotomy for pacemaker lead-induced tricuspid stenosis. AB - Permanent pacemaker lead-induced tricuspid regurgitation is extremely uncommon. We report a patient with severe tricuspid stenosis detected 10 years after permanent single chamber pacemaker implantation in surgically corrected congenital heart disease. The loop at the level of the tricuspid valve may have caused endothelial injury and eventually led to stenosis. Percutaneous balloon valvotomy for such stenosis has not been reported from India. PMID- 26995418 TI - Native coarctation of aorta and large hypertensive patent ductus arteriosus: Management using a covered stent. PMID- 26995419 TI - Thrombus on pacemaker lead. AB - A 58-year-old male was admitted with history of shortness of breath and recurrent fever since two months. He had undergone permanent pacemaker implantation six years back for complete heart block. The patient was persistently having thrombocytopenia. Echocardiographic examination revealed mass (size 4.28 cm(2)) attached to pacemaker lead in right atrium. The patient was scheduled for open heart surgery for removal of right atrial mass. During surgery, pacemaker leads and pulse generator were also removed along with mass considering the possible source of infection. PMID- 26995420 TI - A new anomaly of the left anterior descending artery: Type X dual LAD. AB - Dual left anterior descending (LAD) coronary artery anomaly is traditionally classified as four types anomaly by classical coronary angiogram. Nowadays, coronary computed tomographic angiography (CCTA) allows clinicians to understand other variants of dual LAD anomaly. Up to date, 9 types of dual LAD variants detected from not only classical coronary angiogram but also CCTA imaging have been reported. In the present case, we aimed to show a novel dual LAD anomaly, which is demonstrated by CCTA during preoperative evaluation and it has not been previously reported. PMID- 26995421 TI - Recurrent chest pain after treatment of spontaneous coronary artery dissection: An enigma. AB - Spontaneous coronary artery dissection (SCAD) is a rare entity. It has been described in various settings like pregnancy, collagen vascular diseases, cocaine abuse, heavy exercise, variant angina, eosinophilic arteritis, or fibro muscular dysplasia. It is also easy to miss a dissection during angiography, as the typical radiolucent lumen seen in coronary angiography may be absent in many cases. In this report, we describe the case of a 35-year-old female who presented with acute ST elevation myocardial infarction due to spontaneous coronary dissection. She had been having episodic chest pain for one year and had been seen by two different cardiologists but was thought to have non-cardiac symptoms. Even during the index hospitalization, she underwent coronary angiography three times before coronary dissection could be identified as the cause of her symptoms. She underwent coronary artery bypass graft surgery uneventfully. However, even after myocardial revascularization, she has had multiple episodes of chest pain requiring hospitalization. However, we have not been able to find a specific cause for it and the cause of her recurrent chest pain remains an enigma. This case highlights the problems, which arise while managing a case of SCAD. More research is needed to find the exact etiology and long-term prognosis of this condition. PMID- 26995422 TI - Double ventricular rupture after acute myocardial infarction: A rare case report. AB - A previously asymptomatic 53-year-old male presented 5 days after an acute anterior wall myocardial infarction, who was fibrinolytic naive, with worsening dyspnea. Transthoracic echocardiographic evaluation revealed rupture of the interventricular septum and pseudoaneurysm of the left ventricle, confirmed by angiography. Coronary angiogram revealed multivessel disease. The patient underwent successful closure of ventricular septal rupture with repair of pseudoaneurysm and saphenous vein grafts to posterior descending branch of right coronary artery and obtuse marginal branch of left circumflex artery. Double ventricular ruptures following acute myocardial infarction are very rare with a reported incidence of 0.3% from various series in the revascularization era. They are also associated with exceedingly high mortality rates reaching up to 50%, even when intervened emergently. PMID- 26995423 TI - Anomalous twin circumflex artery in a 47-year-old Indian female. AB - Anomalous origin of circumflex coronary is not an uncommon finding. However, dual origin of circumflex artery is a rare anomaly. An extensive literature search indicates that there have been only three such prior reports. We report the first such case from the Indian subcontinent. This was diagnosed by conventional angiography and CT angiography. PMID- 26995424 TI - Successful surgical management of atherosclerotic dual right coronary artery with short-term follow-up. AB - Congenital anomalies of the coronary arteries are present in 0.2-1.4% of the general population. Dual right coronary artery is one of the rarest congenital anomalies (0.01%) of the coronary arteries. We report a patient with unstable angina with severe triple vessel disease who had diseased dual right coronary artery. He was successfully managed with surgical revascularization and followed up with computed tomography angiography. Surgical revascularization of both the coronary arteries of right side is hardly reported in literature. PMID- 26995426 TI - Perclose Closure Device breakage and embolization during deployment followed by retrieval with snare. AB - Perclose Closure Device (Abbott-Vascular) was attempted for femoral artery (FA) access site closure by an experienced operator. The device was felt to snap as it was pushed through the previously scarred skin and subcutaneous tissue. Perclose had broken into two pieces with the proximal portion outside the body and the distal portion embolizing to lie in the FA to distal aorta. The left FA was accessed through 8F sheath and 4-8mm Basket snare passed through a 6F multipurpose guiding catheter. The tip of the broken Perclose was caught with the snare and pulled out. The Perclose has a distal flexible sheath that is overmolded directly onto the proximal rigid guide. This junction of sheath and guide may be a weak point. Accidental pressure applied at this weak point in any Perclose device during deployment can cause breakage. Awareness of this rare complication is important for safety. PMID- 26995425 TI - Spontaneous subdural hematoma and antiplatelet therapy: Does efficacy of Ticagrelor come with added risk? AB - Antiplatelet therapy has established clinical benefit on cardiovascular outcome and has reduced the rates of re-infarction/in stent thrombosis following percutaneous coronary intervention in acute coronary syndromes. Major bleeding episodes can occur with antiplatelet therapy and intracranial hemorrhage (ICH) is one of the most feared complications resulting in significant morbidity and mortality. Identification of high risk groups and judicious use of antiplatelet therapy reduces the bleeding risk. Ticagrelor is a newer P2Y12 receptor antagonist with established clinical benefit. However, risks of having an ICH with these newer molecules cannot be ignored. Here, we report a case of spontaneous acute subdural hematoma developing in a patient on antiplatelet therapy with aspirin and ticagrelor. Early recognition, discontinuation of the medication and appropriate management resulted in resolution of hematoma and good clinical outcome. Authors have reviewed the antithrombotic drugs and their tendencies in causing intracranial bleeds from a neurophysicians perspective. PMID- 26995428 TI - There's something about that name: Nomenclature of anomalous coronary arteries. PMID- 26995427 TI - Dual-artery stenting of a type III single coronary artery from right aortic sinus. AB - A single coronary artery presenting with stenosis in two of the three vessels arising from a common ostium is a rare anomaly Lipton et al. proposed a classification, which was modified by Yamanaka and Hobbs. In our case, a single coronary artery was giving rise to the LAD, left circumflex (LCx), and the right coronary artery (RCA). There was 80% stenosis in the ostium of the LCx. The RCA in the mid and distal segment had stenosis of 80% and 70%, respectively. We were able to successfully stent the three stenotic segments. PMID- 26995429 TI - Percutaneous intervention of chronic total occlusion of anomalous right coronary artery originating from left sinus - Use of mother and child technique using guideliner. AB - Anomalous origin of right coronary artery (RCA) from left sinus is a rare clinical entity. Percutaneous coronary intervention of such an anomalous RCA, which is chronically occluded, is difficult and is rarely described. We describe such an intervention in a patient, who had a chronic total occlusion of anomalous RCA and discuss the technical issues associated with such interventions. PMID- 26995430 TI - The 'MAP strategy' (Maximum aspiration of atherothrombus and adjunctive glycoprotein IIb/IIIa inhibitor utilization combined with prolonged inflation of balloon/stent) for preventing no-reflow in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: A retrospective analysis of seventy-one cases. AB - 'No-reflow' phenomenon is a common occurrence in percutaneous coronary intervention (PCI). A three-component 'MAP strategy' was designed to prevent no reflow by addressing both intralesional and intraluminal thrombus in patients with ST-segment elevation myocardial infarction (STEMI). In this analysis, we observed Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 or 2 in all patients, with no incidence of no-reflow. Myocardial blush grade (MBG) 3 or 2 was observed in most (87.32%) patients. Left ventricular ejection fraction (LVEF) was improved, without any incidence of death up to 9-month follow-up. All patients safely tolerated the strategy-driven prolonged, 35-s inflation of the balloon/stent. PMID- 26995431 TI - Percutaneous coronary intervention in a rare variety of single coronary artery. AB - We present a case of 50-year-old male having unstable angina. A rare type of single coronary artery was identified during the Coronary angiogram. The left anterior descending (LAD) and left circumflex artery (LCX) had originated from the proximal segment of right coronary artery along with significant lesion in LCX. Computed tomographic (CT) coronary angiogram confirmed the origin and course following which successful percutaneous coronary intervention (PCI) was done to LCX. The incidence of this type of coronary anomaly is 0.004%. We emphasize the importance of having a CT coronary angiogram to identify the course before the intervention. The procedural risk during PCI in patients with single coronary ostium is high. Moreover, the angulation and course of the culprit artery also pose a challenge. Good coaxial guide support by using an appropriate guiding catheter is the key to success. PMID- 26995432 TI - Broken guidewire - A tale of three cases. AB - Guidewire fracture is a rare complication of percutaneous coronary intervention. Retained guide wire fragments in the coronary tree can cause thrombosis, embolic phenomena, dissection, perforation, and vessel occlusion. The management of this complication is still debated and it involves conservative management of leaving wire alone, percutaneous retrieval of fractured fragment, use of second stent to crush the wire, or open heart surgery. Here, I am reporting three cases of broken guidewire and they have been managed in three different ways. PMID- 26995433 TI - Rasmussen's aneurysm: A rare and forgotten cause of hemoptysis. AB - Hemoptysis as a sequelae of past tubercular infection of lungs is a known occurrence. Hemoptysis in such a patient can result from a number of etiologies like tubercular reactivation, bronchiectasis, aspergiloma and vascular complications like hypervascularity from bronchial arteries, arteriovenous fistula formation, pseudoaneurysms, etc. Massive hemoptysis in such a patient is usually treated by bronchial artery embolization and occasionally by surgical lobectomy. A rare source of bleeding in such a patient is from Rasmussen's aneurysm arising from the pulmonary arteries. We report a young patient of treated pulmonary tuberculosis who had recurrent hemoptysis. He was treated earlier with bronchial artery embolization. On recurrence of hemoptysis, he was reevaluated and was found to have multiple Rasmussen's aneurysms arising from the pulmonary arteries, which were successfully treated by coil embolization. PMID- 26995434 TI - Hybrid approach in a difficult case of pseudoaneurysm of right common carotid artery. AB - We present the case of a 65-year-old gentleman, who presented with a symptomatic pseudoaneurysm of the right common carotid artery. Because of high surgical risk, endovascular approach was decided upon. However, taking hardware across the lesion via the aortic arch provided us with insurmountable difficulties. Therefore, a hybrid approach was resorted to, in which an arteriotomy was done in the carotid artery followed by direct implantation of the stent. We were thus able to create a favorable trade-off between the high surgical risk of a full surgical procedure and the peri-operative benefit of an endovascular approach. PMID- 26995436 TI - How to manage a case of aymptomatic thoraco-abdominal aortic aneurysm with occluded mesenteric arteries. AB - We report a unique case of a 57-year-old male having a suprarenal thoraco abdominal aortic aneurysm which is extending till the origin of superior mesenteric artery (SMA). The origins of celiac artery and SMA were totally occluded and filled retrogradely through dense collateral vessels arising from the inferior mesenteric artery. Surprisingly, the patient was not having any symptoms related to mesenteric ischemia. We decided to use a conventional aortic aneurysm stent graft to repair it without revascularizing the occluded mesenteric arteries. After 1 month, CT aortogram was repeated which revealed a well-apposed stent graft with no endoleaks. He did not have any clinical signs and symptoms attributable to mesenteric ischemia. PMID- 26995435 TI - Emergent endovascular stent grafting for saccular arch aneurysm complicated by aorto-esophageal fistula. AB - Aneurysms of aortic arch are rare but amenable to endovascular therapy. Arch aneurysm presenting with aorto-esophageal fistula and hematemesis is a feared, but relatively rare complication. The extrapolation of the safety and rapidity of emergent endovascular repair for bleeding arch aneurysms has been infrequently reported. A bovine arch anatomy confers distinct advantages for endovascular therapy often avoiding a preceding debranching surgery. However, its endovascular treatment might be complicated by the nonhealing of fistula and potential risk for mediastinitis. Here, we report a case of a bovine aortic arch cystic aneurysm complicated by bleeding aorto-esophageal fistula, which warranted an emergent endovascular therapy. The prevertebral part of LSCA was plugged to interrupt the retrograde filling and a future endoleak. A nonhealing aorto-mediastinal fistula at follow-up was successfully treated by covered esophageal stenting. This report reiterates the importance of multidisciplinary approach with multispecialty collaboration to such complex spectrum of diseases. PMID- 26995437 TI - Catheter-directed thrombolysis in management of postpartum lower limb deep venous thrombosis - A case series. AB - Deep vein thrombosis (DVT) is a major health problem in pregnancy and postpartum period. Catheter-directed thrombolysis (CDT) is safe and effective in the management of symptomatic DVT. Value of CDT in postpartum DVT is not fully evaluated. We describe five patients presenting with acute iliofemoral DVT in their early postpartum period who were treated with mechanical thromboaspiration and CDT. The CDT was done using streptokinase infusion and unfractionated heparin. Percutaneous angioplasty was done in patients with symptomatic residual lesion following thrombolysis. Patients were discharged with oral anticoagulant and compression stockings. This approach was successful in all five cases. Percutaneous endovascular therapy using CDT, mechanical thromboaspiration, and balloon angioplasty is safe and effective in iliofemoral DVT in postpartum period. PMID- 26995439 TI - Renal denervation in a patient with Alport syndrome and rejected renal allograft. AB - Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation. PMID- 26995438 TI - Dual antiplatelet therapy and newer agents: More efficacy but lets keep the brain safe!! PMID- 26995440 TI - Transcatheter device closure of multiple defects in ruptured sinus of Valsalva aneurysm. AB - Ruptured sinus of Valsalva aneurysm (SOVA) with multiple communications, ventricular septal defect, and aortic regurgitation are still best treated surgically. We report a case of 30-year-old male with right SOVA, with two communications with right ventricle. Both communications were successfully closed using antegrade and retrograde approaches, respectively. PMID- 26995441 TI - Balloon dilatation of isolated severe tricuspid valve stenosis. AB - Tricuspid valve stenosis is mostly rheumatic in origin. It almost always occurs in association with mitral valve disease. There are only few case reports of isolated tricuspid valve stenosis. We report a case of isolated tricuspid valve stenosis, which was treated with balloon dilatation. PMID- 26995442 TI - Simultaneous transcatheter closure of ruptured sinus of Valsalva aneurysm and stent implantation for aortic coarctation. AB - Ruptured sinus of Valsalva aneurysm is a rare anomaly and an associated coarctation of aorta is even rarer. A combination of such defects is traditionally treated surgically. The surgery is necessarily staged and done through different approaches. We report successful simultaneous transcatheter treatment of both these defects performed in the same setting in an acutely ill adult male patient with a good intermediate-term follow-up. PMID- 26995443 TI - Device closure of patent ductus arteriosus in interrupted inferior vena cava. AB - INTRODUCTION: A 3-year-old child, weighing 8 kg, presented with patent ductus arteriosus (PDA) and interrupted inferior vena cava (IVC). The patient underwent successful PDA device closure via transjugular route after failing attempt at femoral venous route. CASE SUMMARY: PDA device closure was attempted via femoral venous route but could not be accomplished due to difficult curves to negotiate. Following this, PDA could be closed by device from jugular venous route with ease. DISCUSSION: Interrupted IVC poses challenges for PDA device closure and various alternative routes are described like internal jugular, transhepatic, or femoral venous - azygous route. Our case describes difficulties associated with femoral venous route and advantages of jugular venous route in such cases. CONCLUSION: Internal jugular access is a safe and feasible method of PDA device closure in cases of interrupted IVC even in smaller children. PMID- 26995444 TI - Removal of the broken part of implantable cardioverter-defibrillator's electrode causing pulmonary embolism via femoral vein. AB - A 66-year-old patient with idiopathic dilated cardiomyopathy underwent transvenous extraction of an implantable cardioverter-defibrillator. The distal part of the electrode was broken during manual traction through the left subclavian vein. In the present case, we showed a rare complication of transvenous lead extraction and its management. PMID- 26995445 TI - Medial subclavicular musculotendinous complex and insulation break: Rare cause of late pacemaker lead malfunction. AB - Insulation break in a permanent pacemaker lead is a rare long-term complication. We describe an elderly male with a VVIR pacemaker, who presented with an episode of presyncope more than 3 years after the initial implantation procedure, attributed to insulation break possibly caused by lead entrapment in components of the medial subclavicular musculotendinous complex (MSMC) and repeated compressive damage over time during ipsilateral arm movement requiring lead replacement. The differential diagnosis of a clinical presentation when pacing stimuli are present with failure to capture and the role of the MSMC in causing lead damage late after implantation are discussed. PMID- 26995446 TI - A novel use of EP catheter in extraction of trapped intracardiac devices: Two case reports. AB - The decision to retrieve chronically implanted abandoned leads and trapped intracardiac devices percutaneously has been difficult and highly controversial. We present two case reports in which electrophysiological ablation catheter was used to retrieve infected abandoned pacemaker lead and trapped permacatheter (permacath) in right ventricle. We could avert major cardiovascular surgeries in both the patients by simply modifying the traditionally used techniques for extraction of intracardiac devices. PMID- 26995447 TI - New left ventricular active fixation lead: The experience of lead extraction. AB - Left ventricular active fixation lead is fundamental for targeted pacing site. The challenge is the extraction but in our experience Attain((r)) StabilityTM was removed without any problem. As usual the lead can cause a thrombosis of the coronary vein but we performed a venoplasty in order to place again a lead in the target site and maintain the CRT response. PMID- 26995448 TI - The Missing Skull - Professor Lundborg and the mismeasure of grandma. AB - What is science? Or, more pertinently, what is good science? This question is central for all practitioners of science and one of the most important to convey to our students. For those of us working in interdisciplinary settings - my own department covers everything from humanities to political and natural science - the question becomes even more complicated when traditions from different disciplines collide. For me personally, whenever I think too highly of my own research and risk deviating into bad scientific practices, I think of my paternal grandmother, Elsa. Although long dead, she brings me back into the fold of good science - or so I hope - by urging me to take another turn at critically evaluating how I perform research and to keep my arrogance in check. PMID- 26995449 TI - Chemical transformation of CO2 during its capture by waste biomass derived biochars. AB - Biochar is a porous carbonaceous material with high alkalinity and rich minerals, making it possible for CO2 capture. In this study, biochars derived from pig manure, sewage sludge, and wheat straw were evaluated for their CO2 sorption behavior. All three biochars showed high sorption abilities for CO2, with the maximum capacities reaching 18.2-34.4 mg g(-1) at 25 degrees C. Elevating sorption temperature and moisture content promoted the transition of CO2 uptake from physical to chemical process. Mineral components such as Mg, Ca, Fe, K, etc. in biochar induced the chemical sorption of CO2 via the mineralogical reactions which occupied 17.7%-50.9% of the total sorption. FeOOH in sewage sludge biochar was transformed by sorbed CO2 into Fe(OH)2CO3, while the sorbed CO2 in pig manure biochar was precipitated as K2Ca(CO3)2 and CaMg(CO3)2, which resulted in a dominant increase of insoluble inorganic carbon in both biochars. For wheat straw biochar, sorbed CO2 induced CaCO3 transformed into soluble Ca(HCO3)2, which led to a dominant increase of soluble inorganic carbons. The results obtained from this study demonstrated that biochar as a unique carbonaceous material could distinctly be a promising sorbent for CO2 capture in which chemical sorption induced by mineralogical reactions played an important role. PMID- 26995450 TI - Drospirenone intake alters plasmatic steroid levels and cyp17a1 expression in gonads of juvenile sea bass. AB - Drospirenone (DRO) is one of the most widely used progestins in contraceptive treatments and hormone replacement therapies. The pharmacokinetics and potential toxicological effects of DRO were investigated in juvenile sea bass (Dicentrarchus labrax) exposed through the diet (0.01-10 MUg DRO/g) for up to 31 days. DRO was detected in the blood (4-27 ng/mL) of fish exposed to the highest concentration, with no significant bioaccumulation over time and no alteration of hepatic metabolizing enzymes, namely, CYP1A and CYP3A-catalysed activities and UDP-glucuronyltransferase (UGT). Pregnenolone (P5), progesterone (P4), 17alpha hydroxyprogesterone (17P4), 17alpha-hydroxypregnenolone (17P5), androstenedione (AD) and testosterone (T) were determined in plasma and gene expression of cyp17a1, cyp19a1a and cyp11beta analysed by qRT-PCR in gonads. The significant increase in plasmatic levels of 17P5, 17P4 and AD detected after 31 days exposure to 10 ng DRO/g together with the increased expression of cyp17a1 in females evidence the ability of DRO to alter steroid synthesis at low intake concentrations (7 ng DRO/day). However, the potential consequences of this steroid shift for female reproduction remain to be investigated. PMID- 26995451 TI - Arbuscular mycorrhizal wheat inoculation promotes alkane and polycyclic aromatic hydrocarbon biodegradation: Microcosm experiment on aged-contaminated soil. AB - Very few studies reported the potential of arbuscular mycorrhizal symbiosis to dissipate hydrocarbons in aged polluted soils. The present work aims to study the efficiency of arbuscular mycorrhizal colonized wheat plants in the dissipation of alkanes and polycyclic aromatic hydrocarbons (PAHs). Our results demonstrated that the inoculation of wheat with Rhizophagus irregularis allowed a better dissipation of PAHs and alkanes after 16 weeks of culture by comparison to non inoculated condition. These dissipations observed in the inoculated soil resulted from several processes: (i) a light adsorption on roots (0.5% for PAHs), (ii) a bioaccumulation in roots (5.7% for PAHs and 6.6% for alkanes), (iii) a transfer in shoots (0.4 for PAHs and 0.5% for alkanes) and mainly a biodegradation. Whereas PAHs and alkanes degradation rates were respectively estimated to 12 and 47% with non-inoculated wheat, their degradation rates reached 18 and 48% with inoculated wheat. The mycorrhizal inoculation induced an increase of Gram positive and Gram-negative bacteria by 56 and 37% compared to the non-inoculated wheat. Moreover, an increase of peroxidase activity was assessed in mycorrhizal roots. Taken together, our findings suggested that mycorrhization led to a better hydrocarbon biodegradation in the aged-contaminated soil thanks to a stimulation of telluric bacteria and hydrocarbon metabolization in mycorrhizal roots. PMID- 26995454 TI - Corrigendum. PMID- 26995452 TI - Effect of pH and soil structure on transport of sulfonamide antibiotics in agricultural soils. AB - We investigated the effect of solution pH and soil structure on transport of sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) in combination with batch sorption tests and column experiments. Sorption isotherms properly conformed to Freundlich model, and sorption potential of the antibiotics is as follows; sulfadimethoxine > sulfamethoxazole > sulfamethazine. Decreasing pH values led to increased sorption potential of the antibiotics on soil material in pH range of 4.0-8.0. This likely resulted from abundance of neutral and positive-charged sulfonamides species at low pH, which electrostatically bind to sorption sites on soil surface. Due to destruction of macropore channels, lower hydraulic conductivities of mobile zone were estimated in the disturbed soil columns than in the undisturbed soil columns, and eventually led to lower mobility of the antibiotics in disturbed column. The results suggest that knowledge of soil structure and solution condition is required to predict fate and distribution of sulfonamide antibiotics in environmental matrix. PMID- 26995453 TI - Weathering steel as a potential source for metal contamination: Metal dissolution during 3-year of field exposure in a urban coastal site. AB - Surface and building runoff can significantly contribute to the total metal loading in urban runoff waters, with potential adverse effects on the receiving ecosystems. The present paper analyses the corrosion-induced metal dissolution (Fe, Mn, Cr, Ni, Cu) from weathering steel (Cor-Ten A) with or without artificial patinas, exposed for 3 years in unsheltered conditions at a marine urban site (Rimini, Italy). The influence of environmental parameters, atmospheric pollutants and surface finish on the release of dissolved metals in rain was evaluated, also by means of multivariate analysis (two-way and three-way Principal Component Analysis). In addition, surface and cross-section investigations were performed so as to monitor the patina evolution. The contribution provided by weathering steel runoff to the dissolved Fe, Mn and Ni loading at local level is not negligible and pre-patination treatments seem to worsen the performance of weathering steel in term of metal release. Metal dissolution is strongly affected by extreme events and shows seasonal variations, with different influence of seasonal parameters on the behaviour of bare or artificially patinated steel, suggesting that climate changes could significantly influence metal release from this alloy. Therefore, it is essential to perform a long-term monitoring of the performance, the durability and the environmental impact of weathering steel. PMID- 26995455 TI - New light upon your shoulder--ICSES 2016. PMID- 26995456 TI - The American Society of Shoulder and Elbow Therapists' consensus statement on rehabilitation following arthroscopic rotator cuff repair. AB - This is a consensus statement on rehabilitation developed by the American Society of Shoulder and Elbow Therapists. The purpose of this statement is to aid clinical decision making during the rehabilitation of patients after arthroscopic rotator cuff repair. The overarching philosophy of rehabilitation is centered on the principle of the gradual application of controlled stresses to the healing rotator cuff repair with consideration of rotator cuff tear size, tissue quality, and patient variables. This statement describes a rehabilitation framework that includes a 2-week period of strict immobilization and a staged introduction of protected, passive range of motion during weeks 2-6 postoperatively, followed by restoration of active range of motion, and then progressive strengthening beginning at postoperative week 12. When appropriate, rehabilitation continues with a functional progression for return to athletic or demanding work activities. This document represents the first consensus rehabilitation statement developed by a multidisciplinary society of international rehabilitation professionals specifically for the postoperative care of patients after arthroscopic rotator cuff repair. PMID- 26995457 TI - Factors associated with operative treatment of enthesopathy of the extensor carpi radialis brevis origin. AB - BACKGROUND: This study investigated the factors associated with variation in the rate of surgery for enthesopathy of the extensor carpi radialis brevis (eECRB). METHODS: We used a large database from 3 academic hospitals including 5964 patients with the diagnosis of eECRB from 2001 to 2007. Of those, 244 patients (4%) had surgery for eECRB. We used the date of the first encounter as the date of diagnosis. We also recorded the date of the first cortisone injection and surgery for eECRB. We used Cox multivariable regression analysis to find factors associated with surgery. We considered the following explanatory factors: age, sex, race, diabetes, a diagnosis of major depression, a diagnosis of an anxiety disorder, hospital, provider (surgeon vs. nonsurgeon), corticosteroid injection, and the time from diagnosis to the first cortisone injection. RESULTS: The hazard ratio of having surgery was 12-times greater if the initial provider was an orthopedic surgeon rather a nonsurgeon and 1.7-times greater at 1 of the 2 hospitals. The rate of surgery varied substantially, ranging from 0% to 22%. Corticosteroid injection delayed the time to surgery but was ultimately associated with a higher rate of surgery. The majority (86%) of surgeries were done within 1 year of the first documented office visit. CONCLUSIONS: It seems likely that an emphasis on the preferences and values of the patient rather than the surgeon would decrease the variation in surgery rates for eECRB observed in this study. Methods for optimizing the influence of patient preferences and values on decision making (eg, decision aids) merit additional study. PMID- 26995458 TI - Major League Baseball pitch velocity and pitch type associated with risk of ulnar collateral ligament injury. AB - BACKGROUND: The number of Major League Baseball (MLB) pitchers requiring ulnar collateral ligament (UCL) reconstructions is increasing. Recent literature has attempted to correlate specific stresses placed on the throwing arm to risk for UCL injury, with limited results. METHODS: Eighty-three MLB pitchers who underwent primary UCL reconstruction were evaluated. Pitching velocity and percent of pitch type thrown (fastball, curve ball, slider, and change-up) were evaluated 2 years before and after surgery. Data were compared with control pitchers matched for age, position, size, innings pitched, and experience. RESULTS: The evaluation of pitch velocity compared with matched controls found no differences in pre-UCL reconstruction pitch velocities for fastballs (91.5 vs. 91.2 miles per hour [mph], P = .69), curveballs (78.2 vs. 77.9 mph, P = .92), sliders (83.3 vs. 83.5 mph, P = .88), or change-ups (83.9 vs. 83.8 mph, P = .96). When the percentage of pitches thrown was evaluated, UCL reconstructed pitchers pitch significantly more fastballs than controls (46.7% vs. 39.4%, P = .035). This correlated to a 2% increase in risk for UCL injury for every 1% increase in fastballs thrown. Pitching more than 48% fastballs was a significant predictor of UCL injury, because pitchers over this threshold required reconstruction (P = .006). CONCLUSION: MLB pitchers requiring UCL reconstruction do not pitch at higher velocities than matched controls, and pitch velocity does not appear to be a risk factor for UCL reconstruction. However, MLB pitchers who pitch a high percentage of fastballs may be at increased risk for UCL injury because pitching a higher percent of fastballs appears to be a risk factor for UCL reconstruction. PMID- 26995459 TI - Surgical management of congenital elbow instability: a case report. PMID- 26995460 TI - Misalignment of the clavicle after intramedullary fixation of a midshaft fracture with a titanium elastic nail results in acute neurovascular thoracic outlet syndrome. PMID- 26995461 TI - Cardiomyocyte-endothelial cell control of lipoprotein lipase. AB - In people with diabetes, inadequate pharmaceutical management predisposes the patient to heart failure, which is the leading cause of diabetes related death. One instigator for this cardiac dysfunction is change in fuel utilization by the heart. Thus, following diabetes, when cardiac glucose utilization is impaired, the heart undergoes metabolic transformation wherein it switches to using fats as an exclusive source of energy. Although this switching is geared to help the heart initially, in the long term, this has detrimental effects on cardiac function. These include the generation of noxious byproducts, which damage the cardiomyocytes, and ultimately result in increased morbidity and mortality. A key perpetrator that may be responsible for organizing this metabolic disequilibrium is lipoprotein lipase (LPL), the enzyme responsible for providing fat to the hearts. Either exaggeration or reduction in its activity following diabetes could lead to heart dysfunction. Given the disturbing news that diabetes is rampant across the globe, gaining more insight into the mechanism(s) by which cardiac LPL is regulated may assist other researchers in devising new therapeutic strategies to restore metabolic equilibrium, to help prevent or delay heart disease seen during diabetes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 26995462 TI - The role of CD36 in the regulation of myocardial lipid metabolism. AB - Since the heart has one of the highest energy requirements of all organs in the body, it requires a constant and plentiful supply of fuel to function properly. Mitochondrial oxidation of lipids provides a major source of ATP for the heart, and the cellular processes that regulate lipid uptake and utilization are important contributors to maintaining proper myocardial energetic status. Although numerous proteins are coordinately regulated in order to ensure proper fatty acid utilization in the cardiomyocyte, a key first step in this process is the entry of fatty acids into the cell. An important protein involved in the transport of fatty acids into the cardiomyocyte is the plasma membrane-associated protein known as fatty acid translocase (FAT; also known as CD36). While multiple proteins are involved in facilitating fatty acid uptake in the heart, CD36 accounts for approximately 50-70% of the total fatty acid taken up in cardiomyocytes. As such, myocardial metabolism of fatty acids may depend upon proper CD36 function. Consistent with this, changes in CD36 levels/function have been implicated in the alteration of myocardial metabolism in the pathophysiology of certain cardiovascular diseases. As such, a better understanding of the role and function of CD36 in the heart may provide important insights for the development of new treatments for specific cardiovascular diseases. Herein, we review the role of CD36 in myocardial lipid metabolism in the healthy heart and describe how CD36-mediated alterations in lipid metabolism may contribute to cardiovascular disease. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 26995464 TI - Prognostic and prescriptive predictors of improvement in a naturalistic study on inpatient and day hospital treatment of depression. AB - BACKGROUND: The study aimed to identify prognostic (associated with general outcome) and prescriptive (associated with differential outcome in two different settings) predictors of improvement in a naturalistic multi-center study on inpatient and day hospital treatment in major depressive disorder (MDD). METHODS: 250 inpatients and 250 day hospital patients of eight psychosomatic hospitals were assessed at admission, discharge and a 3-months follow-up. Primary outcome was defined as a reduction of depressive symptomatology from admission to discharge and from discharge to follow-up (QIDS-C, total score). Percent improvement scores at discharge and at follow-up were entered as dependent variables into two General Linear Models with a set of predictor variables and the respective interaction terms with treatment setting. The selection of predictor sets was guided by statistical methods of variable preselection (LASSO). RESULTS: Three variables were associated with less improvement from admission to discharge: the number of additional axis-I diagnoses, axis-II co morbidity (SCID) and lower motivation (expert assessment). Social support (F SozU) predicted symptom course between discharge and 3-month follow-up. Patients with no absent / sick days prior to admission showed a less favorable symptom course after discharge when treated as inpatients. CONCLUSIONS: Patients with co morbidity show less improvement during the active treatment phase. Motivation can be considered a prerequisite for symptom reduction, whereas social support seems to be an important factor for the maintenance of treatment gains. The lack in prescriptive predictors found may point to the fact that inpatient and day hospital treatment have comparable effects for most subgroups of patients with MDD. PMID- 26995463 TI - Roles for lipid heterogeneity in immunoreceptor signaling. AB - Immune receptors that specifically recognize foreign antigens to activate leukocytes in adaptive immune responses belong to a family of multichain cell surface proteins. All of these contain immunoreceptor tyrosine-based activation motifs in one or more subunits that initiate signaling cascades following stimulated tyrosine phosphorylation by Src-family kinases. As highlighted in this review, lipids participate in this initial activation step, as well as in more downstream signaling steps. We summarize evidence for cholesterol-dependent ordered lipids serving to regulate the store-operated Ca(2+) channel, Orai1, and we describe the sensitivity of Orai1 coupling to the ER Ca(2+) sensor, STIM1, to inhibition by polyunsaturated fatty acids. Phosphoinositides play key roles in regulating STIM1-Orai1 coupling, as well as in the stimulated Ca(2+) oscillations that are a consequence of IgE receptor signaling in mast cells. They also participate in the coupling between the plasma membrane and the actin cytoskeleton, which regulates immune receptor responses in T cells, B cells, and mast cells, both positively and negatively, depending on the cellular context. Recent studies show that other phospholipids with mostly saturated acylation also participate in coupling between receptors and the actin cytoskeleton. Lipid heterogeneity is a central feature of the intimate relationship between the plasma membrane and the actin cytoskeleton. The detailed nature of these interactions and how they are dynamically regulated to initiate and propagate receptor-mediated cell signaling are challenging questions for further investigation. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26995465 TI - Early symptom measurement of Post-Stroke Depression (PSD). AB - BACKGROUND: We reported the factor structure and psychometric properties of a new measure of early symptoms of Post-Stroke Depression (PSD). METHODS: Cross sectional survey methods were used to administer the measure to hospitalized post stroke patients (N=410) in southeast China, 7-30 days after mild to moderate stroke. Factor structure of the measure was evaluated using exploratory factor analysis (EFA) with first and second order confirmatory factor analysis (CFA). Measurement reliability of each factor and the total measure was assessed using Cronbach alpha coefficient, item-total correlation, item-subscale correlation and the composite coefficient. Discriminant validity was tested using the estimated correlation matrix and average variance extracted (AVE). RESULTS: The EFA extracted a theoretically consistent, clinically interpretable, 29-item, 6-factor model for early symptoms of PSD (dull, guilt, low, wakefulness, emotional, and nervous). A first order CFA retained the 6-factors but deleted 3 underperforming items. The results of a second-order CFA for a 6-factor, 26-item model showed acceptable model fit (chi(2)/df=2.25, CFI=0.973, TLI=0.970, RMSEA=0.055 and WRMR=1.168) with acceptable reliability and discriminant validity. LIMITATIONS: The study survey methods and purposive sampling procedures resulted in a clinically less homogenous final sample. Separate evaluation of predictive validity, criteria validity, test-retest reliability, and invariance to patient psychosocial characteristics of the measure is planned. CONCLUSIONS: Our measure detected early symptoms of PSD in primarily first-ever stroke patients, an average of 11.07 days post stroke, well within the 14 day peak benchmark. PMID- 26995466 TI - Developmental trajectories of self-injurious behavior, suicidal behavior and substance misuse and their association with adolescent borderline personality pathology. AB - OBJECTIVE: Adolescent risk-taking and self-harm behaviors are associated with affect dysregulation and impulsivity, both core features of borderline personality disorder (BPD). We hypothesized that the developmental courses of these behaviors i) tend to cluster rather than appear individually, and ii) might indicate adolescent BPD pathology. Therefore, we explored the developmental trajectories of self-injurious behavior (SIB), suicidal behavior (SB) and substance misuse (SM) in a community sample of adolescents; and we investigated the trajectories' overlap and its associations with BPD traits. METHOD: 513 adolescents, aged 15-17 years, were followed for two years as part of the Saving and Empowering Young Lives in Europe study and its subsequent follow-up. Distinct developmental trajectories were explored using general growth mixture modeling. RESULTS: Three distinct classes were identified within each of the harmful behaviors SIB, SB and SM. Both the high-risk SIB trajectory and the high-risk SB trajectory demonstrated elevated initial degree of engagement, followed by a gradual decrease. The SM high-risk trajectory had a medium initial degree of engagement, which increased over time. There was a high degree of overlap (80 90%) among the high-risk trajectories for the three behaviors (SIB, SB and SM), and this overlap was significantly associated with elevated levels of BPD pathology. LIMITATIONS: The data collection was based on participants' self report. CONCLUSION: The findings indicate a similar pattern of reduction over time between SIB and SB for the high-risk trajectories, whereas the high-risk trajectories for SM show a pattern of increase over time. The observed symptom shift is associated with borderline personality pathology in adolescents. Therefore these behaviors might represent early indicators of risk supporting potential early detection. PMID- 26995469 TI - The editorial term of Professor Henry Walton (Volumes 10-31). PMID- 26995467 TI - The effect of pain on presence and severity of depressive disorders in older persons: The role of perceived control as mediator. AB - BACKGROUND: The relation between pain and depression is reported repeatedly. It is suggested that pain by itself is not sufficient for the development of depression. We aim to study the role of perceived control as mediating factor in the relation between pain and depressive disorders at old age. METHODS: Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used, including 345 persons with DSM-IV depressive disorders (CIDI) and 125 control persons without depressive disorders, aged 60 years and over. Measures included severity of depression (Inventory of Depressive Symptomatology), presence and intensity of pain and pain-related disability (Chronic Graded Pain scale), and a general measure of perceived control over life (Pearlin Mastery Scale). In mediation analyses direct and indirect effects were estimated. RESULTS: Older persons with depressive disorders reported pain more frequently with higher intensity than controls. After controlling for confounding, the direct effect of pain intensity and the indirect effect through perceived control on depression were OR=1.10 (CI 95% .98;1.25) and OR=1.24 (1.15;1.35). For pain-related disability these were OR=1.14 (1.02;1.29) and OR=1.21 (1.13;1.29). In depressed persons there was a strong direct effect of pain intensity and disability and a smaller indirect effect through perceived control on severity of depressive symptoms. LIMITATIONS: This cross-sectional study cannot give evidence on causal direction. CONCLUSIONS: Perceived control plays an important role as mediator in the association between pain and presence of depression. In depressed persons however, the direct role of pain seems more important in the association with depression severity. PMID- 26995470 TI - Revisiting 'Assessment of clinical competence using an objective structured clinical examination (OSCE)'. PMID- 26995471 TI - Literature reviews in the health professions: It's all about the theory. PMID- 26995472 TI - Quality and literature reviews: beyond reporting standards. PMID- 26995473 TI - Tips for a great review article: crossing methodological boundaries. PMID- 26995474 TI - Context matters: groupthink and outcomes of health care teams. PMID- 26995475 TI - Fit for purpose? Selection processes should consider aptitude in terms of skills, personal characteristics and context. PMID- 26995476 TI - The dangers of assuming the generalisability of non-technical skills. PMID- 26995477 TI - Are all peer tutors and their tutoring really effective? Considering quality assurance. PMID- 26995478 TI - Being a good supervisor: it's all about the relationship. PMID- 26995479 TI - When I say ... literature reviews. PMID- 26995480 TI - Are we at risk of groupthink in our approach to teamwork interventions in health care? AB - CONTEXT: The incidence of medical error, adverse clinical events and poor quality health care is unacceptably high and there are data to suggest that poor coordination of care, or teamwork, contributes to adverse outcomes. So, can we assume that increased collaboration in multidisciplinary teams improves performance and health care outcomes for patients? METHODS: In this essay, the authors discuss some reasons why we should not presume that collective decision making leads to better decisions and collaborative care results in better health care outcomes. RESULTS: Despite an exponential increase in interventions designed to improve teamwork and interprofessional education (IPE), we are still lacking good quality data on whether these interventions improve important outcomes. There are reasons why some of the components of 'effective teamwork', such as shared mental models, team orientation and mutual trust, could impair delivery of health care. For example, prior studies have found that brainstorming results in fewer ideas rather than more, and hinders rather than helps productivity. There are several possible explanations for this effect, including 'social loafing' and cognitive overload. Similarly, attributes that improve cohesion within groups, such as team orientation and mutual trust, may increase the risk of 'groupthink' and group conformity bias, which may lead to poorer decisions. CONCLUSIONS: In reality, teamwork and IPE are not inherently good, bad or neutral; instead, as with any intervention, their effect is modified by the persons involved, the situation and the interaction between persons and situation. Thus, rather than assume better outcomes with teamwork and IPE interventions, as clinicians and educators we must demonstrate that our interventions improve the delivery of health care. PMID- 26995481 TI - The predictive value of aptitude assessment in laparoscopic surgery: a meta analysis. AB - CONTEXT: Current methods of assessing candidates for medical specialties that involve laparoscopic skills suffer from a lack of instruments to assess the ability to work in a minimally invasive surgery environment. OBJECTIVES: A meta analysis was conducted to investigate whether aptitude assessment can be used to predict variability in the acquisition and performance of laparoscopic skills. METHODS: PubMed, PsycINFO and Google Scholar were searched to November 2014 for published and unpublished studies reporting the measurement of a form of aptitude for laparoscopic skills. The quality of studies was assessed with QUADAS-2. Summary correlations were calculated using a random-effects model. RESULTS: Thirty-four studies were found to be eligible for inclusion; six of these studies used an operating room performance measurement. Laparoscopic skills correlated significantly with visual-spatial ability (r = 0.32, 95% confidence interval [CI] 0.25-0.39; p < 0.001), perceptual ability (r = 0.31, 95% CI 0.22-0.39; p < 0.001), psychomotor ability (r = 0.26, 95% CI 0.10-0.40; p = 0.003) and simulator based assessment of aptitude (r = 0.64, 95% CI 0.52-0.73; p < 0.001). Three dimensional dynamic visual-spatial ability showed a significantly higher correlation than intrinsic static visual-spatial ability (p = 0.024). CONCLUSIONS: In general, aptitude assessments are associated with laparoscopic skill level. Simulator-based assessment of aptitude appears to have the potential to represent a job sample and to enable the assessment of all forms of aptitude for laparoscopic surgery at once. A laparoscopy aptitude test can be a valuable additional tool in the assessment of candidates for medical specialties that require laparoscopic skills. PMID- 26995482 TI - Meta-analysis and review of learner performance and preference: virtual versus optical microscopy. AB - CONTEXT: Over nearly two decades, a wealth of literature describing the various capabilities, uses and adaptations of virtual microscopy (VM) has been published. Many studies have investigated the effects on and benefits to student learning of VM compared with optical microscopy (OM). OBJECTIVES: This study statistically aggregated the findings of multiple comparative studies through a meta-analysis in order to summarise and substantiate the pedagogical efficacy of teaching with VM. METHODS: Using predefined eligibility criteria, teams of paired researchers screened the titles and abstracts of VM studies retrieved from seven different databases. After two rounds of screening, numerical and thematic data were extracted from the eligible studies for analysis. A summary effect size and estimate of heterogeneity were calculated to determine the effects of VM on learner performance and the amount of variance between studies, respectively. Trends in student perceptions were also analysed and reported. RESULTS: Of the 725 records screened, 72 studies underwent full-text review. In total, 12 studies were viable for meta-analysis and additional studies were reviewed to extract themes relating to learners' perceptions of VM. The meta-analysis detected a small yet significant positive effect on learner performance (standardised mean difference 0.28, 95% confidence interval 0.09-0.47; p = 0.003), indicating that learners experience marked knowledge gains when exposed to VM over OM. Variation among studies was evident as high heterogeneity was reported. An analysis of trends in learner perceptions noted that respondents favoured VM over OM by a large margin. CONCLUSIONS: Although many individual studies have reported non significant findings in comparisons of VM and OM, the enhanced power afforded by meta-analysis revealed that the pedagogical approach of VM is modestly superior to that of OM and is preferred by learners. PMID- 26995483 TI - Non-technical skills and health care provision in low- and middle-income countries: a systematic review. AB - CONTEXT: Health care workers must possess high levels of medical knowledge, technical skills and also non-technical skills (NTS) in order to provide safe, effective and patient-centred care. Although there has been a recent proliferation of NTS assessment and training tools developed in high-income countries, little is known about NTS in low- and middle-income countries (LMICs), which face a variety of provider-level and system-level challenges. The aim of this study was to identify the NTS used by providers in LMICs that have been studied, describe how they are assessed and taught, and explain the contextual factors in LMICs that affect their use. METHODS: We conducted a systematic literature review in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines for primary research publications from January 1994 to December 2013 on evaluation or teaching of NTS used by health care workers in LMICs using MEDLINE, Embase, CIHHAL and Web of Science. Bibliographies of relevant manuscripts were also hand-searched to identify all potentially eligible manuscripts. RESULTS: We identified 21 manuscripts from 17 LMICs involving eight types of health care providers and trainees. These studies covered five NTS categories: decision making, communication, teamwork, leadership and stress management. The most commonly used methods were questionnaires, interviews and observations, and 43% (n = 9) scored > 10 points using the Medical Education Research Study Quality Instrument. Although many studies highlighted the ways in which overburdened health care systems, lack of provider empowerment and deficiencies in provider training had an impact on providers' use of these NTS, no context-specific assessment or educational tools were identified. CONCLUSION: There is growing worldwide interest in understanding and teaching critical non-technical skills to health care providers. This review highlights several studies describing a variety of important non-technical skills. However, these skills must be further characterised in order to develop context-specific tools for assessing and teaching NTS that are sensitive to the local challenges that are common across a variety of LMIC contexts. PMID- 26995484 TI - Prevalence of depression amongst medical students: a meta-analysis. AB - CONTEXT: Medical schools are known to be stressful environments for students and hence medical students have been believed to experience greater incidences of depression than others. We evaluated the global prevalence of depression amongst medical students, as well as epidemiological, psychological, educational and social factors in order to identify high-risk groups that may require targeted interventions. METHODS: A systematic search was conducted in online databases for cross-sectional studies examining prevalences of depression among medical students. Studies were included only if they had used standardised and validated questionnaires to evaluate the prevalence of depression in a group of medical students. Random-effects models were used to calculate the aggregate prevalence and pooled odds ratios (ORs). Meta-regression was carried out when heterogeneity was high. RESULTS: Findings for a total of 62 728 medical students and 1845 non medical students were pooled across 77 studies and examined. Our analyses demonstrated a global prevalence of depression amongst medical students of 28.0% (95% confidence interval [CI] 24.2-32.1%). Female, Year 1, postgraduate and Middle Eastern medical students were more likely to be depressed, but the differences were not statistically significant. By year of study, Year 1 students had the highest rates of depression at 33.5% (95% CI 25.2-43.1%); rates of depression then gradually decreased to reach 20.5% (95% CI 13.2-30.5%) at Year 5. This trend represented a significant decline (B = - 0.324, p = 0.005). There was no significant difference in prevalences of depression between medical and non medical students. The overall mean frequency of suicide ideation was 5.8% (95% CI 4.0-8.3%), but the mean proportion of depressed medical students who sought treatment was only 12.9% (95% CI 8.1-19.8%). CONCLUSIONS: Depression affects almost one-third of medical students globally but treatment rates are relatively low. The current findings suggest that medical schools and health authorities should offer early detection and prevention programmes, and interventions for depression amongst medical students before graduation. PMID- 26995485 TI - Same-level peer-assisted learning in medical clinical placements: a narrative systematic review. AB - BACKGROUND: Peer-assisted learning (PAL) is increasingly used in medical education, and the benefits of this approach have been reported. Previous reviews have focused on the benefits of peer tutoring of junior students by senior students. Forms of PAL such as discussion groups and role-playing have been neglected, as have alternative teacher-learner configurations (e.g. same-level PAL) and the effects on other stakeholders, including clinician educators and patients. This review examines the benefits of same-level PAL for students, clinician educators and patients in pre-registration clinical medical education. METHODS: Medline, PsycINFO, CINAHL and ERIC were searched in March 2014. A total of 1228 abstracts were retrieved for review; 64 full-text papers were assessed. Data were extracted from empirical studies describing a same-level PAL initiative in a clinical setting, focusing on effects beyond academic performance and student satisfaction. Qualitative thematic analysis was employed to identify types of PAL and to cluster the reported PAL effects. RESULTS: Forty-three studies were included in the review. PAL activities were categorised into role play, discussion, teaching and assessment. Only 50% of studies reported information beyond self-report and satisfaction with the PAL intervention. Benefits for students (including development of communication and professional skills) and clinician educators (developing less-used facilitation skills) were reported. Direct patient outcomes were not identified. Caveats to the use of PAL emerged, and guidelines for the use of PAL were perceived as useful. CONCLUSION: Many student-related benefits of PAL were identified. PAL contributes to the development of crucial skills required for a doctor in the workplace. Vertical integration of learning and teaching skills across the curriculum and tools such as feedback checklists may be required for successful PAL in the clinical environment. Benefits for patients and educators were poorly characterised within the included studies. Future work should evaluate the use of PAL with regards to student, clinician educator and patient outcomes. PMID- 26995487 TI - Erratum. PMID- 26995486 TI - Competencies to enable learning-focused clinical supervision: a thematic analysis of the literature. AB - CONTEXT: Clinical supervision is essential for development of health professional students and widely recognised as a significant factor influencing student learning. Although considered important, delivery is often founded on personal experience or a series of predetermined steps that offer standardised behavioural approaches. Such a view may limit the capacity to promote individualised student learning in complex clinical environments. The objective of this review was to develop a comprehensive understanding of what is considered 'good' clinical supervision, within health student education. The literature provides many perspectives, so collation and interpretation were needed to aid development and understanding for all clinicians required to perform clinical supervision within their daily practice. METHOD: A comprehensive thematic literature review was carried out, which included a variety of health disciplines and geographical environments. RESULTS: Literature addressing 'good' clinical supervision consists primarily of descriptive qualitative research comprising mostly small studies that repeated descriptions of student and supervisor opinions of 'good' supervision. Synthesis and thematic analysis of the literature resulted in four 'competency' domains perceived to inform delivery of learning-focused or 'good' clinical supervision. Domains understood to promote student learning are co dependent and include 'to partner', 'to nurture', 'to engage' and 'to facilitate meaning'. CONCLUSIONS: Clinical supervision is a complex phenomenon and establishing a comprehensive understanding across health disciplines can influence the future health workforce. The learning-focused clinical supervision domains presented here provide an alternative perspective of clinical supervision of health students. This paper is the first step in establishing a more comprehensive understanding of learning-focused clinical supervision, which may lead to development of competencies for clinical supervision. PMID- 26995488 TI - Evaluation of the immunogenicity of the 13-valent conjugated pneumococcal vaccine in rheumatoid arthritis patients treated with etanercept. AB - OBJECTIVES: To prospectively evaluate the immunogenicity of a 13-valent conjugated pneumococcal vaccine (PCV13) in rheumatoid arthritis (RA) patients undergoing etanercept therapy. METHODS: Twenty-two RA patients treated with etanercept (ETA) in combination with methotrexate (MTX) (n=15) or monotherapy (n=7) for at least one year were included. Altogether 24 osteoarthritis patients not receiving biological or MTX therapy, treating only NSAIDs or analgesics served as controls. All subjects were vaccinated with a single dose (0.5ml) of the PCV13. Pneumococcal antibody levels at baseline, 4 and 8weeks were assessed by a VaccZymeTM Anti-PCP IgG Enzyme Immunoassay Kit. Based on recommendations of the American Academy of Allergy, Asthma & Immunology, an at least two-fold increase in antibody level, as the protective antibody response (pAR) was an indicator of responsiveness (i.e., ratio of postvaccination and prevaccination antibody levels). The antibody levels and their ratios were analysed in a variety of different ways, vaccine safety parameters (fever, infections, changes in regular antirheumatic treatments) were assessed at baseline, 4 and 8weeks after vaccination. RESULTS: Four weeks after vaccination, the anti-pneumococcal antibody levels significantly increased in both groups. At week 8, antibody levels somewhat decreased in both groups, however, still remained significantly higher compared to baseline. Compared with postvaccination levels at 4 and 8weeks between two groups, the mean protective antibody levels were higher in control group (1st month P=0.016; 2nd month: P=0.039). Possible predictors of pAR were analysed by logistic regression model. In RA, increases of antibody levels at week 8 compared to baseline exerted a negative correlation with age, (Spearman's R=-0,431; P=0.045). There were no clinically significant side effects or reaction after administration of vaccine observed in any of these patients after the 2 month follow-up period, all patients medical condition were stable. CONCLUSIONS: In RA patients treated with ETA, vaccination with PCV13 is effective and safe, resulting in pAR one and two months after vaccination. Higher age at vaccination was identified as predictors of impaired pAR. The efficacy of vaccination may be more pronounced in younger RA patients. The vaccine is safe in RA patients on ETA. PMID- 26995489 TI - Becoming visible - Experiences from families participating in Family Health Conversations at residential homes for older people. AB - Having a sick family member living at a residential home for older people can be difficult for families, who as a result often suffer from feelings of forsakenness and powerlessness. In response, the purpose of this study was to illuminate family members' experiences with participating in Family Health Conversations at residential homes for older persons 6 months after concluding the conversation series. Twenty-two family members who participated in the conversations later took part in group interviews, the texts of which were analyzed according to qualitative content analysis. Findings showed that participating in Family Health Conversations mediated consolation, since within such a liberating communicative interaction, family members for the first time felt visible as persons with individual significance. Family members reported a positive experience involving both being open to each other and speaking and listening to each other in a new, structured way. As a result, families were able to discover their family members' problems and suffering, as well as to identify their family's resources and strengths. PMID- 26995490 TI - Diagnostic application of recombinant non-structural protein 3A to detect antibodies induced by foot-and-mouth disease virus infection. AB - Detection of antibodies to the non-structural proteins (NSPs) of FMD virus (FMDV) is the preferred differential diagnostic method for identification of FMD infected animals in the vaccinated population. Nevertheless, due to the observed variability in the antibody response to NSPs, the likelihood of screening or confirming the FMD infection status in animals is increased if an antibody profile to multiple NSPs is considered for diagnosis. In order to develop and evaluate an additional NSP-based diagnostic assay, in this study, the recombinant 3A protein of FMDV was expressed in Escherichia coli and used as an antigen for detection of FMD infection specific antibodies. At the fixed cut-off value of 45 percentage of positivity, the diagnostic sensitivity and specificity of 3A indirect-ELISA (I-ELISA) were found to be 95.7% and 96.3%, respectively. In FMD naturally infected cattle, about 85% of clinically infected and 75% of asymptomatic in-contact populations were found positive at 13 months post outbreak. The 3A I-ELISA was further evaluated with the bovine serum samples collected randomly from different parts of the country. Furthermore, the performance of newly developed 3A I-ELISA was compared with the extensively used in-house r3AB3 I-ELISA, and the overall concordance in test results was found to be 93.62%. The r3A I-ELISA could be useful as a screening or confirmatory assay in the sero-surveillance of FMD in India irrespective of extensive bi-annual vaccination. PMID- 26995491 TI - The shy prefer familiar congeners. AB - The shy-bold continuum is both a fundamental aspect of human behavior and a relatively stable behavioral trait for many other species. Here we assessed whether shy individuals prefer familiar congeners, taking the European sea bass, a recently domesticated fish showing similar behavioral responses to wild fish, as a model to better understand the inter-individual variability in social behavior previously observed in this species. In the wild, the link between familiarity i.e., the preference of fish for familiar congeners and boldness could be part of the mechanism underlying shoaling formation in fish. Thirty fish were individually tested in a device designed to assess the preference for a familiar vs. an unfamiliar congener on the basis of visual cues only. An open field test (OFT) with shelter was performed on the same fish 32 days later to assess the boldness of each individual. Variables of interest included the proportion of time spent in the shelter, border and center zone of the arena and variables of activity. Variables measured in OFT were collapsed into first principal component scores using Principal Components Analysis (PCA) which allowed characterizing a shy-bold continuum. Time spent near the familiar congener was negatively correlated with boldness i.e., shy individuals spent most of the time near the familiar congener. We discuss the relevance of these findings to the understanding of the behavior of European sea bass and suggest that the link between familiarity and shyness is a general aspect of both animal and human behavior. PMID- 26995492 TI - Volumetric imaging with homogenised excitation and static field at 9.4 T. AB - OBJECTIVES: To overcome the challenges of B0 and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B0 and flip-angle homogenisation was implemented on a human 9.4 T scanner. MATERIALS AND METHODS: Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B0- and B1-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B0 shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T1- and T 2 (*) -weighted images with MPRAGE and 3D EPI, respectively. RESULTS: Over six in vivo acquisitions, the B0 distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10 +/- 0.01 ppm (39 +/- 2 Hz). Utilising the kT points pulses, the normalised RMSE of the excitation was decreased from CP-mode's 30.5 +/- 0.9 to 9.2 +/- 0.7 % with all B 1 (+) voids eliminated. The SNR inhomogeneities and contrast variations in the T1- and T 2 (*) -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T1-weighted image. CONCLUSION: A 15-minute B0- and flip-angle homogenisation workflow, including the B0- and B1-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images. PMID- 26995493 TI - Laparoscopic Versus Laparotomic Surgical Staging for Early-Stage Ovarian Cancer: A Case-Control Study. AB - STUDY OBJECTIVE: To evaluate the oncologic outcomes of patients with early-stage ovarian cancer (eOC) managed by laparoscopy or laparotomy in a single high-volume gynecologic cancer center. DESIGN: Retrospective case-control study (Canadian Task Force classification II-2). SETTING: Catholic University of the Sacred Hearth, Rome, Italy. PATIENTS: Data of consecutive women with eOC undergoing comprehensive laparoscopic staging between 2007 and 2013 were matched with a cohort of patients undergoing open surgery between 2000 and 2011. Four-year survival outcomes were analyzed using the Kaplan-Meier method. MEASUREMENTS AND RESULTS: Sixty women undergoing staging via laparoscopy were compared with a cohort of 120 patients undergoing open surgery. Baseline characteristics were similar between groups. Seventy percent of patients underwent adjuvant platinum based chemotherapy without differences between the 2 groups. Operative time (p = .01), estimated blood loss (p = .032), and median hospital stay (p = .001) were higher in patients submitted to laparotomic versus laparoscopic staging. As of October 2015, median duration of follow-up was 38 months (range, 24 -48), recurrent disease was documented in 16 patients (13.3%) in the laparotomic group and in 5 patients (8.3%) in the laparoscopic group (p = .651), without differences in the pattern of recurrence presentation. Four-year progression-free survival (PFS) and overall survival (OS) rates were 89% and 92% in the laparoscopic group, respectively, and 81% and 91% in the laparotomic group, without any statistical significant difference between the groups (4-year PFS p = .651; 4-year OS p = .719). CONCLUSION: The findings of the present study suggests that in the surgical treatment of FIGO stage I ovarian cancer, laparoscopy is associated with equivalent oncologic outcome compared with a conventional abdominal approach. PMID- 26995495 TI - Molecular characterization of Sp110 gene in pigs. AB - Speckled 110 kDa (Sp110) plays an important role in infectious diseases, as revealed by studies in humans. However, little is known regarding porcine Sp110. To elucidate its potential role in porcine resistance to viral diseases, here, the complete coding sequence of porcine Sp110 gene and its 26 alternatively spliced isoforms were isolated using reverse transcription (RT)-polymerase chain reaction (PCR), and another seven splicing patterns were obtained using a minigene construct. Subcellular distribution of 11 representative isoforms was characterized in PK-15 cells transiently transfected with their respective GFP fusion constructs, and only isoforms (R and V) bearing all functional domains were localized in nucleus, indicating all the other isoforms lose normal functions of Sp110 owing to alternative splicing. Real-time quantitative PCR and competitive RT-PCR showed that both isoforms R and V had similar tissue expression profile, half-life and response to poly(I:C), a synthetic analog of viral double-stranded RNA, while the longer one (isoform R) was transcribed at a higher level. The results indicated that porcine Sp110 has a role in viral infection and that isoform R is the dominant active form. Overall the data provide potential resource for molecular breeding of pig resistant to diseases and contributes to breeding pigs resistant to viral infection. PMID- 26995494 TI - High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke. AB - Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17beta-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2 treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke. PMID- 26995496 TI - Recent progress in structure and dynamics of dual-membrane-spanning bacterial nanomachines. AB - Advances in hard-ware and soft-ware for electron cryo-microscopy and tomography have provided unprecedented structural insights into large protein complexes in bacterial membranes. Tomographic volumes of native complexes in situ, combined with other structural and functional data, reveal functionally important conformational changes. Here, we review recent progress in elucidating the structure and mechanism of dual-membrane-spanning nanomachines involved in bacterial motility, adhesion, pathogenesis and biofilm formation, including the type IV pilus assembly machinery and the type III and VI secretions systems. We highlight how these new structural data shed light on the assembly and action of such machines and discuss future directions for more detailed mechanistic understanding of these massive, fascinating complexes. PMID- 26995497 TI - Predictors of prolonged fluoroscopy time in diagnostic coronary angiography. AB - BACKGROUND: Prolonged fluoroscopy time during coronary angiography is a major concern for interventional cardiologists as well as for patients. It is unknown which factors affect the prolonged fluoroscopy time. METHODS: A total of 458 patients who underwent diagnostic coronary angiography were included. The patients who had the highest decile of fluoroscopy time were assigned to the prolonged fluoroscopy group (fluoroscopy time >=15.7min), while the other patients were assigned to the non-prolonged fluoroscopy group (fluoroscopy time <15.7min). We performed univariate and multivariate logistic regression analysis to identify the predictors of prolonged fluoroscopy time. RESULTS: Mean fluoroscopy time in 458 patients was 8.5+/-5.8min. Median and ranges of fluoroscopy time were 19.0 [15.7-47.0]min in the prolonged fluoroscopy group and 6.0 [2.0-15.3]min in the non-prolonged fluoroscopy group, respectively. The multivariate logistic regression analysis showed that significant predictors of prolonged fluoroscopy time were prior surgery of ascending aorta replacement [odds ratios (OR) 11.46, 95% confidence intervals (CI) 1.53-85.74, p=0.02] and the prevalence of moderate to severe aortic regurgitation (OR 2.83, 95% CI 1.20 6.66, p=0.02). CONCLUSIONS: The prior surgery of ascending aorta replacement and moderate to severe aortic regurgitation were significant predictors of the prolonged fluoroscopy time. PMID- 26995498 TI - The histological characteristics and virtual histology findings of the tissues obtained by a distal protection device during endovascular therapy for peripheral artery disease. AB - BACKGROUND: Distal embolization (DE) is one of the most serious complications of endovascular therapy (EVT). The purpose of the present study was to characterize the lesions that indicate a high risk of DE in patients undergoing EVT, and to investigate the pathological characteristics of the debris. METHODS: Seventy three consecutive patients with peripheral artery disease (PAD) underwent EVT with a filter device. Image analyses using grayscale intravascular ultrasound (IVUS) and virtual histology (VH) IVUS were performed and the large debris that was trapped was subjected to histological, immunohistochemical, and immunofluorescence analyses. RESULTS: Sixty-nine patients were successfully treated with a filter device (iliac artery, n=46; femoral artery, n=23). Large debris, which was defined as debris of >2mm in maximal diameter, was confirmed in 33 of 69 patients (48%) and was trapped more frequently in the iliac artery than in the femoral artery. Histological analyses were not performed in 36 of 69 patients (52%) because the debris particles were too small to investigate (<2mm in maximal diameter). The proportion of large debris was significantly higher in lesions with ulceration than in lesions without ulceration (p<0.001). The necrotic core (NC) was significantly more developed in the large debris group than in the small debris group (p<0.05). White thrombi were observed in most of the debris particles, and not only the inflammatory component, but also the stable component caused distal embolisms. Inflammatory cells, mainly CD68 positive cells that were also positive for myeloperoxidase, were observed in approximately half of the debris particles. CONCLUSIONS: Distal protection during EVT would be considered when the lesion is located in the iliac artery, is an ulcerative lesion, and when VH-IVUS determines that the lesion contains NC. The plaque in PAD patients mainly corresponds to the stable phenotype; however, it may also exhibit the characteristics of the vulnerable phenotype. PMID- 26995499 TI - A prospective study predicting the outcome of chronic low back pain and physical therapy: the role of fear-avoidance beliefs and extraspinal pain. AB - OBJECTIVE: To identify the prognostic factors for conventional physical therapy in patients with chronic low back pain (CLBP). METHODS: Prospective observational study. PARTICIPANTS: One hundred thirteen patients with CLBP selected at the Spinal Disease Outpatient Clinic. MAIN OUTCOME MEASURES: Pain intensity was scored using the Numeric Rating Scale (NRS), and function was measured using the Roland-Morris Disability Questionnaire (RMDQ). RESULTS: The Fear-Avoidance Beliefs Questionnaire work subscale results (FABQ-work; odds ratio [OR]=0.27, 95% confidence interval [CI] 0.13 to 0.56, p<0.001) and extraspinal pain (OR=0.35, 95% CI 0.17 to 0.74, p=0.006) were independently associated with a decreased response to conventional physical therapy for CLBP. CONCLUSION: We identified high FABQ-work and extraspinal pain scores as key determinants of a worse response to physical therapy among CLBP patients, supporting the need for a special rehabilitation program for this subgroup. PMID- 26995500 TI - Relapsing polychondritis and lymphocytic meningitis with varied neurological symptoms. PMID- 26995501 TI - Spontaneous anterior arch fracture of the atlas following C1 laminectomy without fusion: A report of three cases and finite element analysis. AB - BACKGROUND: Only four cases of anterior arch fracture after C1 laminectomy without fusion have been previously reported. Although atlas fractures commonly occur in response to high-energy trauma, no obvious trauma that could cause the fracture was observed in these reported cases. The purpose of this study was to elucidate the biomechanical mechanism of anterior arch fracture of the atlas following C1 laminectomy and present three cases of this fracture. METHODS: Three cases of fracture of the anterior arch of the atlas following C1 laminectomy were retrospectively reviewed. Three atlas models (an intact model, a laminectomy model, and a transverse ligament-resected model) were created from computed tomography data of each case using a three-dimensional finite element method. Axial load was applied on the superior facet to mimic four conditions (neutral, flexion, extension, lateral bending). The distribution of von Mises stress in the anterior arch and the displacement of the posterior arch were compared among the three models. RESULTS: In all three cases, the anterior arch fracture clinically occurred after C1 laminectomy despite there being no obvious inciting trauma. During the finite element analysis, increased stress was observed in all postures of the laminectomy model as compared with the intact model. The stress concentrated location observed in the finite element model was consistent with the fracture sites that were clinically observed. In terms of loading condition, much higher stress was observed in extension and lateral bending as compared with other postures. There were no significant differences in stress distribution between the laminectomy model and the transverse ligament-resected laminectomy model. CONCLUSIONS: Stress distribution concentrates in the anterior arch after C1 laminectomy, leading to fracture of the anterior arch despite no inciting trauma. There may be more frequent occult fractures observed after C1 laminectomy than has been reported. Therefore, surgeons should recognize anterior arch fracture as a possible complication of C1 laminectomy without fusion. PMID- 26995502 TI - Review of the Literature: A Rural-Urban Comparison of Social Networks of Older Adults Living With HIV. AB - Globally, aging populations and older persons living with HIV (OPLWH) are emerging socioeconomic and health care concerns. Aging adults living in rural communities have less access to and lower utilization of health care services; they rely heavily on available peer and family networks. Although social networks have been linked to positive mental and physical health outcomes, there is a lack of understanding about social networks in rural-dwelling OPLWH. The purpose of this integrative literature review was to compare emerging themes in the social network components of rural versus urban-dwelling OPLWH and network benefits and barriers. Overarching themes include: limited and/or fragile networks, social inclusion versus social isolation, social capital, and health outcomes. Results demonstrate an overall lack of rural-focused research on OPLWH and a universal lack of informal and formal networks due to isolation, lack of health care services, and omnipresent HIV stigma. PMID- 26995503 TI - Combined phacoemulsification and XEN45 surgery from a temporal approach and 2 incisions. AB - OBJECTIVE: To assess the safety and effectiveness of phacoemulsification combined with XEN45 implant surgery in patients with cataract and open-angle glaucoma, with 12-month follow-up. METHODS: A prospective study conducted on 30 eyes requiring phacoemulsification with, at least, 2 medications to control intraocular pressure (IOP). Phacoemulsification combined with XEN45 implant surgery was performed within 15minutes of administering subconjunctival mitomycin C. Surgery was performed through 2 temporal incisions, separated by 90 degrees , using the inferior to enter the XEN45 and to implant it in the superior nasal region. A record was made of the best corrected visual acuity, IOP before and 1 day, 1 month, 3 months, 6 months, 9 months, and 12 months after surgery, the number of antiglaucomatous medications, and complications. RESULTS: The best corrected visual acuity was 0.37+/-0.2 and 0.72+/-0.15 before and 12 months after surgery, respectively. The pre-operative IOP was 21.2+/-3.4mmHg, with 3.07 drugs, decreasing by 61.65% on the first day, 37.26% at 1 month, 35.05% at 3 months, 31% at 6 months, 30.6% at 9 months, and 29.34% at 12 months. The number of medications decreased by 94.57%. Complications occurred in 3 eyes, 2 of them were excluded because we could not complete the implantation (280 degrees subconjunctival haemorrhage and XEN extrusion when trying to reposition). In a third case, the bleb was encapsulated at 5 months after surgery. CONCLUSIONS: The phacoemulsification combined with XEN45 implant surgery can effectively reduce IOP and the number of drugs in mild-moderate open-angle glaucoma, as they rehabilitate the VA. The use of only 2 micro-invasive incisions makes it simple, quick and safe, with few complications at 12 months follow-up from surgery. PMID- 26995504 TI - Near infrared fluorescent nanoparticles based on hyaluronic acid: Self-assembly, optical properties, and cell interaction. AB - Fluorescent imaging agents that can specifically highlight tumor cells could have a significant impact on image-guided tumor removal. Here, fluorescent nanoparticles (NPs) derived from hyaluronic acid (HA) are investigated. HA is a ligand for the receptor CD44, which is a common biomarker present on many primary tumor cells, cancer-initiating cells, and tumor-associated fibroblasts. In addition, a family of enzymes that degrade HA, called hyaluronidases (HYALs), are also overexpressed with increased activity in many tumors. We report the design and development of a panel of targeted imaging agents using the near-infrared (NIR) dye, Cy7.5, that was directly conjugated to hydrophobically-modified HA. Two different molecular weights of HA, 10kDa and 100kDa, and three different degrees of hydrophobic moiety conjugation (0, 10, and 30mol%) were utilized to develop a panel of NPs with variable size that ranged from 50 to 400nm hydrodynamic diameter (HD) depending HA molecular weight, extent of fluorescence quenching (25-50%), kinetics of cellular uptake, and targeting to CD44+ cells. The kinetics and energy-dependence of cellular uptake in breast and prostate cancer cell lines, MDA-MB 231 and PC-3 cells, respectively, showed increased uptake with longer incubation times (at 4 and 8h compared to 1h), as well as uptake at 37 degrees C but not 4 degrees C, which indicated energy-dependent endocytosis. NP uptake studies in the presence of excess free HA showed that pre treatment of cells with excess high molecular weight (MW) free HA decreased NP uptake by up to 50%, while no such trend was observed with low MW HA. These data lay the foundation for selection of optimized HA-derived NPs for image-guided surgery. STATEMENT OF SIGNIFICANCE: Here, hyaluronic acid (HA), a well-studied biomacromolecule, is modified with a near infrared fluorophore and a hydrophobic moiety. The significance of this work, especially for imaging applications, is that the impact of HA molecular weight and the hydrophobic moiety conjugation degree on fluorescence and cell interaction can be predicted. With respect to existing literature, the eventual use of these HA-based NPs is image-guided surgery; thus, we focus on the dye, Cy7.5, for conjugation, which is more NIR than most existing HA literature. Furthermore, HA is a ligand for CD44, which is associated with cancer and tumor microenvironment cells. Systematic studies in this work highlight that HA can be tuned to maximize or minimize CD44 binding. PMID- 26995505 TI - Redox and pH dual responsive poly(amidoamine) dendrimer-poly(ethylene glycol) conjugates for intracellular delivery of doxorubicin. AB - To solve the contradiction between long circulation time and effective intracellular drug release, redox and pH-responsive drug delivery system was developed by incorporated redox-sensitive disulfide linkage between poly(amidoamine) dendrimers (PAMAM) and poly(ethylene glycol) (PEG). Doxorubicin (DOX) was loaded into the hydrophobic core of the conjugates to prepare PAMAM-SS PEG/DOX complexes (PSSP/DOX). In vitro release studies suggested that DOX release from PSSP/DOX complexes followed an redox and acid-triggered manner and increased with increasing PEGylation degree. In vitro cytotoxicity of PSSP/DOX complexes against B16 tumor cells increased with, while cellular uptake decreased with increasing PEGylation degree. Further, intracellular DOX release observation and measurement indicate that the intracellular DOX release played a critical role for the cytotoxicity of DOX-loaded PSSP conjugates. In addition, cellular entry mechanism of the PSSP/DOX study demonstrated that both clathrin- and caveolae mediated endocytosis were the primary pathways for cellular entry of PSSP/DOX. Finally, in vivo study of PSSP/DOX complexes in B16 tumor-bearing mice indicate that PSSP/DOX could significantly improve antitumor efficiency and present a good safety. The redox and pH-responsive drug delivery system has been demonstrated to be a promising candidate for solid tumor therapy. STATEMENT OF SIGNIFICANCE: In previous research, pH-sensitive diblock polymer of poly(ethylene glycol) poly(2,4,6-trimethoxybenzylidene-pentaerythritol carbonate) (PEG-PTMBPEC) was synthesized to facilitate the intracellular anticancer drug release. However, the nanoparticles based on PEG-PTMBPEC get into the tumor cells just relying on the EPR-mediated passive targeting resulting in the low drug accumulation. Therefore, cRGD peptide modified PEG-PTMBPEC polymeric micelles were developed for specific targeted delivery of doxorubicin (DOX) to neovascular cells and tumor cells simultaneously. The precise intracellular target site and effective drug concentration will contribute to enhancing the antitumor toxicity and reducing the systematic toxicity of DOX. The cRGD modified pH-sensitive micellar system is a promising vehicle for intracellular drug delivery to alphavbeta3 integrin receptor overexpressed tumor cells and neovascular cells. PMID- 26995506 TI - Deletion of Crmp4 attenuates CSPG-induced inhibition of axonal growth and induces nociceptive recovery after spinal cord injury. AB - The capacity for regeneration in the injured adult mammalian central nervous system (CNS) is largely limited by potent inhibitory barriers. Chondroitin sulfate proteoglycans (CSPGs) are major inhibitors of axonal regeneration/sprouting and accumulate at lesion sites after CNS trauma. Despite extensive research during the two decades since their discovery, the molecular mechanisms remain elusive, including intracellular phosphorylation events. Collapsin response mediator protein 4 (CRMP4) is known to directly regulate cytoskeletal dynamics and neurite extension, while phosphorylated CRMP4 loses its binding affinity for cytoskeletal proteins. We have previously found that spinal cord injury (SCI) induces CRMP4 upregulation and phosphorylation and that CRMP4 knockout (Crmp4-/-) mice show behavioral recovery of locomotor function after SCI. However, the role of CRMP4 in the recovery of other forms of physiological function such as sensation remains largely unknown. We here have demonstrated CRMP4 involvement in CSPG-induced inhibitory signaling and nociceptive recovery in Crmp4-/- mice after SCI. We cultured dorsal root ganglion (DRG) neurons on CSPG-coated dishes; Crmp4 deletion overrode CSPG-induced inhibition of axon growth in vitro. CRMP4 levels were increased in DRGs in vivo after SCI. Crmp4-/- mice exhibited axonal growth of sensory neurons and recovery of nociceptive function after spinal transection. These results support Crmp4 deletion as a therapeutic target in the treatment of SCI. PMID- 26995507 TI - tPA promotes cortical neuron survival via mTOR-dependent mechanisms. AB - Tissue plasminogen activator (tPA) is a thrombolytic agent commonly used in the treatment of ischemic stroke. While the thrombolytic effects of tPA have been well established, the impact of this blood-brain barrier (BBB) crossing drug on neurons is not known. Given the widespread use of tPA in the clinical setting and the strict therapeutic window established for effective use of the drug, we examined the molecular mechanisms mediating the impact of tPA on postnatal cortical neurons isolated from the mouse brain. Dissociated postnatal primary cortical neurons were treated with tPA and the effects on neuron survival were evaluated. Pharmacological inhibitors of several signaling pathways previously implicated in neuroprotection (mTOR, JAK/STAT, MAPK and PKA-dependent mechanisms) were used to pinpoint the mechanistic effectors of tPA on neuron survival in vitro. We report here that tPA treatment results in a time-dependent neuroprotective effect on postnatal cortical neurons that relies predominantly on Janus kinase (JAK) and mammalian target of rapamycin (mTOR) signaling mechanisms. Taken together, these data suggest that tPA promotes neuroprotection in a temporally-regulated manner and that both JAK and mTOR signaling effectors are critical mediators of this neuroprotective effect. The results suggest the possibility of targeting these defined mechanisms to potentially expand the therapeutic window for tPA. PMID- 26995508 TI - A Brief Survey of Dietary Beliefs and Behaviors of Pregnant Adolescents. AB - STUDY OBJECTIVE: To provide a brief assessment of dietary beliefs and behaviors in an understudied high-risk population of pregnant adolescents. DESIGN, SETTING, AND PARTICIPANTS: Diverse pregnant adolescents (n = 66) recruited from the Rochester Adolescent Maternity Program at the University of Rochester Medical Center in Rochester, New York completed a nutrition knowledge and beliefs survey once during pregnancy. INTERVENTIONS AND MAIN OUTCOME MEASURES: Responses were recorded by a health project coordinator who had good rapport with the teens. Study staff evaluated responses for emergent themes and thematically coded survey data. All responses were assessed relative to demographic variables using chi(2) and analysis of variance tests. RESULTS: Most (83%; 55/66) pregnant teens self identified as African American with 21% (14/66) identifying as Hispanic. Most (92%; 61/66) adolescents had medical insurance and 28% (19/66) reported participating in the Supplemental Nutrition Program for Women, Infants, and Children. The importance of proper nutrition was acknowledged but 14% (9/66) reported that diet did not matter or they were unsure of the importance of nutrition for the fetus. Money, access to food, and personal relationships were reported as constraining factors for a healthy diet. Response themes did not differ according to demographic characteristics. CONCLUSION: Overall, pregnant teens recognize the importance of dietary intake during pregnancy but this knowledge does not always translate into behaviors. Understanding the health knowledge and behaviors of pregnant adolescents might provide a foundation for future lifestyle and clinical interventions. PMID- 26995509 TI - Isolated Torsion of Accessory Fallopian Tube in a Young Adolescent. AB - BACKGROUND: Accessory fallopian tube is a rare anatomical variation, which might rarely cause gynecological complications such as infertility, ectopic pregnancy, cystic swelling, and pyosalpinx. It is usually diagnosed by surgeons during diagnostic laparoscopy for other purposes. We present a rare case of isolated accessory tube torsion in a young adolescent. CASE: A 16-year-old virgin teen presented with a 24-hour history of aggravating right lower-quadrant abdominal pain and nausea without vomiting or fever. On examination she had right lower quadrant abdominal tenderness with no peritoneal signs. On pelvic ultrasound a right corpus luteum cyst was suspected, but right adnexal torsion could not be ruled out. On laparoscopy, torsion of the right accessory tube was diagnosed. Because of its ischemic and bluish appearance it was removed. The postoperative course was uneventful. Pathology confirmed the diagnosis. SUMMARY AND CONCLUSION: Torsion of an accessory fallopian tube is rare. An English literature search showed that the current case is the third reported overall and the first in a young adolescent. Because of the rarity of this congenital variation, and the low suspicion index for its existence, the diagnosis of accessory tube is often missed. Preventive removal of such findings should be considered but weighed against its possible surgical complications. PMID- 26995510 TI - [Other therapeutic strategies]. AB - Non-selective and irreversible MAOI have become as third or fourth-line strategy for the management of treatment-resistant depression. Non-selective and irreversible MAOI requires careful monitoring of drug interactions and dietary restrictions. Nutritional supplements such as omega-3 have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. The glutamate antagonist ketamine has been found to produce beneficial effects in the management of treatment-resistant depression while administered alone. Dopamine and/or norepinephrine agonists, such as methylphenidate, modafinil or pramipexole, have been found to produce beneficial effects in the management of treatment-resistant depression when administered in combination with the ongoing antidepressant treatment. PMID- 26995511 TI - [Switching and combining strategies of antidepressant medications]. AB - Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects. PMID- 26995512 TI - A novel minimal residual disease model of neuroblastoma in mice. AB - INTRODUCTION: Patients with high-risk neuroblastoma rarely succumb to their primary tumor but rather from relapsed metastatic disease after surgery. We, therefore, sought to create an in vivo model of minimal residual disease (MRD), which clinically replicates tumor recurrence and metastasis after surgical resection. METHODS: Neuroblastoma cell lines CHLA-255, CHLA-136, and SH-SY5Y were used. After establishing orthotopic xenografts, mice were divided into control tumor group (sham operation at 14days) and tumor resection group (resection at 14days). Mice were monitored by bioluminescent imaging and sacrificed when institutional criteria for euthanasia were met. RESULTS: In the CHLA-255 and CHLA 136 cell lines, mice experienced significantly longer survival following tumor resection (p<0.007). There was no survival benefit seen in the SH-SY5Y cell line (p=0.29). Bioluminescent imaging demonstrated metastatic disease in 100% of all tumor resection mice and varying rates of metastasis in control mice (4 of 5 CHLA 255, 2 of 4 CHLA-136, and 7 of 7 SH-SY5Y). CONCLUSION: In this study, we describe a novel neuroblastoma model of MRD in mice. This MRD model serves as an innovative means to test preclinical therapies as well as elucidate mechanisms of metastatic disease in experimental neuroblastoma. PMID- 26995513 TI - Accuracy of radiographic estimation of small bowel dimensions in pediatric patients with short bowel syndrome. AB - BACKGROUND: The decision to perform autologous intestinal lengthening in patients with short bowel syndrome (SBS) depends on total bowel length and the diameter and length of dilated segments. This study evaluated the accuracy of radiologic measurements of intestinal length and diameter. METHODS: Patients who underwent an intestinal lengthening procedure with preoperative upper gastrointestinal study (UGI) were identified from 10/2012 through 1/2015. Measurements of total length and diameters and lengths of dilated segments on UGI were compared to intraoperative measurements using Spearman's rank correlation coefficients and Bland-Altman plots. RESULTS: Fourteen patients underwent 15 lengthening procedures. Median age was 3.6years. Most common causes of SBS were complicated gastroschisis (43%) and small bowel atresia (36%). Intra-operative bowel lengths prior to performing lengthening procedures ranged from 21 to 170cm. The median measurements of radiographic and operative measurements (respectively) were total bowel lengths 77cm and 69cm (r=0.93, p<0.0001), maximum diameters 7.7cm and 7cm (r=0.86, p=0.001), and lengths of dilated segments 13cm and 14cm (r=0.41, p=0.36). CONCLUSIONS: The correlation between UGI and operative measurements suggests that prediction of total bowel length and maximum diameter of dilation is accurate and can assist with operative planning. PMID- 26995514 TI - Long-term renewable human intestinal epithelial stem cells as monolayers: A potential for clinical use. AB - PURPOSE: Current culture schema for human intestinal stem cells (hISCs) frequently rely on a 3D culture system using MatrigelTM, a laminin-rich matrix derived from murine sarcoma that is not suitable for clinical use. We have developed a novel 2D culture system for the in vitro expansion of hISCs as an intestinal epithelial monolayer without the use of Matrigel. METHODS: Cadaveric duodenal samples were processed to isolate intestinal crypts from the mucosa. Crypts were cultured on a thin coat of type I collagen or laminin. Intestinal epithelial monolayers were supported with growth factors to promote self-renewal or differentiation of the hISCs. Proliferating monolayers were sub-cultured every 4-5days. RESULTS: Intestinal epithelial monolayers were capable of long-term cell renewal. Less differentiated monolayers expressed high levels of gene marker LGR5, while more differentiated monolayers had higher expressions of CDX2, MUC2, LYZ, DEF5, and CHGA. Furthermore, monolayers were capable of passaging into a 3D culture system to generate spheroids and enteroids. CONCLUSION: This 2D system is an important step to expand hISCs for further experimental studies and for clinical cell transplantation. LEVEL OF EVIDENCE: 1 Experimental. PMID- 26995515 TI - Liquid chromatography-mass spectroscopy as a tool in the rapid diagnosis of biliary atresia: a pilot study. AB - INTRODUCTION: Biliary atresia (BA) is a neonatal obstructive cholangiopathy requiring rapid intervention to prevent end-stage liver failure and death. Low bile acid levels in stool, detectable with high-performance liquid chromatography mass spectroscopy, may reflect extrahepatic biliary obstruction in cholestasis. HYPOTHESIS: Stool bile acid content can differentiate BA from non-BA forms of cholestasis. METHODS: Stool samples from four healthy and nine cholestatic patients were collected following internal review board approval. Bile acids were extracted and separated on a 4000-Q-Trap HPLC-MS system. RESULTS: Total bile acid content was highest in samples from healthy relative to cholestatic patients: 3354.01 +/- 2102.56, 1476.27 +/- 1361.07, and 34.29 +/- 10.30 MUM/mg of stool in healthy, total parenteral nutrition-associated cholestasis, and BA samples, respectively. Mean cholic acid and chenodeoxycholic acid concentrations in healthy samples (2017.5 +/- 1413.6 and 876.83 +/- 660.60 MUM/mg) were higher than in TPN cholestatic samples (93.99+/-131.55 and 232.34 +/- 293.41 MUM/mg). The most dramatic reduction in cholic acid and chenodeoxycholic acid was observed in BA samples (0.65 +/- 0.47 and 1.22 +/- 0.80 MUM/mg). CONCLUSION: Bile acid content in stool is reduced in cholestatic patients relative to healthy patients with the most dramatic reduction observed in BA-patients. PMID- 26995516 TI - A novel approach to leveraging electronic health record data to enhance pediatric surgical quality improvement bundle process compliance. AB - PURPOSE: Quality improvement (QI) bundles have been widely adopted to reduce surgical site infections (SSI). Improvement science suggests when organizations achieve high-reliability to QI processes, outcomes dramatically improve. However, measuring QI process compliance is poorly supported by electronic health record (EHR) systems. We developed a custom EHR tool to facilitate capture of process data for SSI prevention with the aim of increasing bundle compliance and reducing adverse events. METHODS: Ten SSI prevention bundle processes were linked to EHR data elements that were then aggregated into a snapshot display superimposed on weekly case-log reports. The data aggregation and user interface facilitated efficient review of all SSI bundle elements, providing an exact bundle compliance rate without random sampling or chart review. RESULTS: Nine months after implementation of our custom EHR tool, we observed centerline shifts in median SSI bundle compliance (46% to 72%). Additionally, as predicted by high reliability principles, we began to see a trend toward improvement in SSI rates (1.68 to 0.87 per 100 operations), but a discrete centerline shift was not detected. CONCLUSION: Simple informatics solutions can facilitate extraction of QI process data from the EHR without relying on adjunctive systems. Analyses of these data may drive reductions in adverse events. Pediatric surgical departments should consider leveraging the EHR to enhance bundle compliance as they implement QI strategies. PMID- 26995517 TI - Basic fibroblast growth factor eluting microspheres enhance distraction enterogenesis. AB - PURPOSE: The purpose of this study was to determine if distraction enterogenesis using self-expanding polycaprolactone (PCL) springs is a potential therapy for short bowel syndrome. Sustained release basic fibroblast growth factor (bFGF) microspheres have been shown to induce angiogenesis and intestinal regeneration in tissue engineered scaffolds. We hypothesized that the provision of bFGF-loaded microspheres would increase angiogenesis and thereby enhance the process of enterogenesis. METHODS: A 10-mm segment of rodent jejunum was isolated and an encapsulated PCL spring inserted. Blank or bFGF-loaded microspheres were delivered to the segment. After 4weeks, jejunal segments were assessed for lengthening, morphology, quantification of blood vessels, and ganglia. RESULTS: Lengthened intestinal segments receiving bFGF microspheres demonstrated significantly increased microvascular density compared to those with blank microspheres. There were also significantly more submucosal and myenteric ganglia in the segments that received bFGF microspheres. Segments achieved similar lengthening and final muscular thickness in both blank and bFGF groups, but the bFGF microsphere caused a significant increase in luminal diameter of the jejunal segment. CONCLUSION: Sustained release bFGF microspheres enhanced distraction enterogenesis through improved vascularity. The synergy of growth factors such as bFGF with distraction enterogenesis may yield improved results for the future treatment of patients with short bowel syndrome. PMID- 26995518 TI - Diagnostic imaging practices for children with suspected appendicitis evaluated at definitive care hospitals and their associated referral centers. AB - PURPOSE: The purpose of this study was to compare rates of ultrasound (US) and computed tomography (CT) for suspected appendicitis at hospitals able to provide definitive surgical care with those from their associated referral hospitals. METHODS: A retrospective cohort study of children undergoing appendectomy using the Pediatric NSQIP Appendectomy Pilot Database (1/1/2013-8/31/2014) was performed. Imaging rates at the initial hospital of presentation were compared between groups after adjusting for differences in demographic characteristics. RESULTS: We identified 4859 patients from 28 definitive care hospitals, of which 35% underwent diagnostic imaging at a referral hospital prior to transfer (range: 20.3-70.4%). The overall odds of receiving a CT scan was 10.9-times greater (95% CI: 9.4-12.5) at referring hospitals compared to definitive care hospitals, and the odds were significantly higher for referral hospitals in 96% (27/28) of the geographic regions represented. The overall odds of an initial attempt at US prior to CT was 11.1 times greater (95% CI: 9.09-14.28), and the odds of receiving any ultrasound was 6.25-times greater (95% CI: 5.26-7.14) at definitive care hospitals compared to referral hospitals. CONCLUSIONS: Children initially evaluated for suspected appendicitis at referring hospitals are much more likely to receive a diagnostic CT, and those imaged with CT are much less likely to receive an US as the initial diagnostic test. PMID- 26995519 TI - Reply to letter to the editor. PMID- 26995520 TI - Blood transfusions, increased rates of surgical NEC, and lower survival: a propensity score-matched analysis. AB - PURPOSE: We sought to investigate the association between blood transfusions (BT), rates of necrotizing enterocolitis requiring surgical intervention (SNEC), and survival. METHODS: Blood transfusions in premature infants were identified in the Kids' Inpatient Database (2003-2009). Propensity score-matched analysis compared SNEC outcomes in BT vs. non-BT groups. Multivariate analyses were performed to determine independent predictors of outcome. RESULTS: Overall, 663740 cases were identified and 4.9% received BT. Surgical necrotizing enterocolitis occurred in 493 cases in the BT group, while SNEC occurred in 1049 cases in the non-BT group. Propensity score analysis of 20991 BT and 20988 non-BT cases demonstrated higher SNEC rates with BT (odds ratio [OR], 1.21) vs non-BT. Surgical necrotizing enterocolitis with BT had lower survival rates (58%) vs non BT (67%). Surgical necrotizing enterocolitis with BT had lower length of stay and total charges vs non-BT. On multivariate analyses, SNEC mortality with BT increased for lower gestational age, males (OR, 45.7), African Americans (OR, 64.4), and infants with cardiac anomalies (OR, 50.8) or bronchopulmonary dysplasia (OR, 177). Non-BT SNEC demonstrated higher mortality with lower gestational age and infants with bronchopulmonary dysplasia (OR, 6.56) or sepsis (OR, 3.66). CONCLUSION: On propensity score-matched analysis, SNEC occurs at higher rates after BT and is associated with lower survival and lower resource utilization vs SNEC without BT. PMID- 26995521 TI - Early impact of American College of Surgeons-verification at a level-1 pediatric trauma center. AB - PURPOSE: The purpose of this study was to determine the early impact of American College of Surgeons (ACS)-level-1 verification at an established pediatric trauma center. METHODS: Following IRB approval, we conducted a retrospective review of all trauma patients treated at a level-1 state-designated pediatric trauma center, comparing 2years before (2009-2010) and 2years after ACS-verification (mid-2012-mid-2014). Statistical significance was defined as p<0.05. RESULTS: Before verification, 2105 trauma patients were admitted to our institution compared to 2248 patients admitted after ACS-verification. Overall, there were no differences in mean age or injury severity score (ISS). Hospital and pediatric intensive care unit (PICU) length of stay (LOS), ventilator days, and mortality were also unchanged. Through incorporation of clinical pathways, the number of PICU admissions decreased significantly from 17.2% to 13.7%. Morbidity in the form of hospital-acquired conditions (HACS) also decreased following verification, most notably through reduction in pneumonias. Decubitus ulcers and nosocomial infections reached their nadir by 2014. Hospital readmission rates also decreased. CONCLUSIONS: ACS-verification at a level-1 pediatric trauma center is associated with an immediate benefit to patient outcomes. Enhanced tracking and institutional policy changes resulted in fewer HACS. Further cost saving and improved outcomes because of ACS-verification may be amplified over time. PMID- 26995523 TI - Interdisciplinary approach to esophageal replacement and major airway reconstruction. AB - PURPOSE: Severe esophageal disease warranting replacement often presents with additional airway anomalies in children. Colon interposition and airway reconstruction have separately proven successful in attaining satisfactory outcomes. The aim of this study was to determine outcomes associated with an interdisciplinary approach to care of the patient with complex esophageal and airway disease. METHODS: After IRB approval, a retrospective cohort study was performed spanning 2011 through 2015. Eleven patients underwent colon interposition and airway surgery. Review of medical records was performed, extracting patient demographics, clinical and operative courses and outcomes. RESULTS: The mean age of patients was 44months (range 2-108). 91% (n=10) were transferred to our institution with primary diagnoses of caustic ingestion (45%, n=5), long gap esophageal atresia (27% n=3), tracheoesophageal fistula (18%, n=2) and necrotizing pharyngitis (9% n=1). All patients had associated airway anomalies. Pulmonology, gastroenterology and speech therapy were involved in preoperative evaluation and postoperative care of all patients. Intraoperatively, a multi-team approach was utilized. The most common postoperative complication was esophageal stricture (54%, n=6). All patients are capable of taking some to full nutrition per orum. CONCLUSION: Colonic interposition with major airway reconstruction at our institution attains satisfactory functional results through utilization of a multidisciplinary approach. PMID- 26995522 TI - Initial diagnostic management of pediatric bone tumors. AB - BACKGROUND: Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common primary pediatric bone malignancies. We sought to assess the diagnostic accuracy of initial tumor biopsies in patients with OS or ESFT at a pediatric cancer center. METHODS: All biopsies performed at initial presentation of patients with OS or ESFT at our institution from 2003 to 2012 were retrospectively reviewed. Diagnostic accuracy and incidence of complications were correlated with study variables using logistic regression analysis. RESULTS: One hundred forty-two biopsies were performed in 105 patients (median age 13.4years, range: 1.8-23.0), 104 (73.2%) OS and 38 (27.8%) ESFT. Thirty-one (21.8%) were performed on metastatic sites. Eighty-five (76.6%) of 111 primary site biopsies were open procedures, and 26 were percutaneous (23.4%). Primary site biopsies were successful in 94.1% of open and 73.1% of percutaneous procedures. Odds of obtaining a successful diagnostic specimen were 7.8 times higher with open approach (CI: 1.6-36.8). Metastatic site biopsies were successful in 66.7% of percutaneous and 100% of open and thoracoscopic procedures. CONCLUSION: Biopsy of metastatic sites was equal to primary site in obtaining diagnostic material with the added benefit of accurate staging, with few adverse events and high diagnostic yield. PMID- 26995524 TI - Space occupying lesions in the presence of congenital diaphragmatic hernia. AB - INTRODUCTION: Previous reports describe lung malformations and other chest lesions in association with congenital diaphragmatic hernia (CDH), yet little is known how these lesions affect outcomes. We sought to evaluate the incidence and outcomes of patients diagnosed with chest lesions in association with CDH. METHODS: The charts of all infants treated for CDH in a single tertiary center from January 2004 to January 2015 were reviewed. The outcomes of those with space occupying lesions (SOLs) in association with CDH were compared to those with isolated CDH. Statistical analysis was performed using Student's t-test and Mann Whitney U test for continuous variables and Fisher's exact for categorical variables. RESULTS: Of the 214 infants treated, 20 had an associated SOL (4 had>1 lesion). SOLs were confirmed by pathological examination and included: bronchopulmonary sequestration (n=10; 4.7%), ectopic liver (n=9; 4.2%), foregut duplication cyst (n=2; 1%), and other lesions (n=3; 1.4%). No statistical difference was noted in the long-term outcomes of patients with SOL in comparison to those with isolated CDH. CONCLUSION: SOLs are not uncommon in neonates with CDH. Despite theoretical concerns, there is no evidence that SOLs are associated with worse outcomes, a finding which is helpful during prenatal counseling of families. PMID- 26995525 TI - Evaluation of the Vascular Surgical Complications of Renal Transplantation. AB - BACKGROUND: Renal transplantation is the treatment of choice of end-stage renal failure. However, vascular surgical complications can compromise the functional prognosis of the transplant or even be life threatening in the short term. Since few data are available in the literature, the objective of this study was to evaluate the vascular surgical complications of renal transplantation. METHODS: In a retrospective and monocentric study, the records of all the patients receiving a kidney transplant between January 2008 and December 2014 were reviewed. The demographic data and the follow-up of the patients who presented a vascular surgical complication in relation to their transplant were collected. Minor, intermediate, or major vascular complications were defined according to the need for monitoring, reoperation, or the risk of transplant loss or a life threatening situation. Predictive factors of vascular complications were also looked for. RESULTS: Mean age was 50.9 +/- 15.0 years, and 312 kidney transplants were carried out (205 men). Fifty vascular surgical complications (16.0%) were found. Among them, 23 vascular complications (7.4%) were major, including 6 (1.9%) which required transplantectomy, after 4 arterial thromboses (1.3%), 1 early venous thrombosis (0.3%), and 1 injury of the inferior vena cava (0.3%). Twelve complications (3.8%) were minor. Surgical revision was necessary in 76% of the vascular complications (n = 38). The average follow-up of the transplanted population was 37.4 +/- 24.0 month, 268 kidney transplants (85.8%) were functional and 21 patients (6.7%) returned to dialysis. Surgical complications were more frequent when the recipient had hypertension (P = 0.02, OR = 2.5; 95% CI [1.1-6.1]), in case of right kidney transplant (P = 0.0004, OR = 3.1; 95% CI [1.6-5.8]) and when the kidney hilum consisted of at least arteries (P = 0.02, OR = 10.0; 95% CI [1.3-34]). Male gender (P = 0.03, OR = 0.5; 95% CI [0.3-0.9]) as well as the choice of the common iliac arterial (P = 0.001, OR = 0.4; 95% IC [0.2 0.7]) and venous (P = 0.002, OR = 0.3; 95% IC [0.2-0.8]) axes to carry out the vascular anastomoses appeared as protective factors. CONCLUSIONS: The vascular surgical complications of kidney transplantation, especially thromboses, can be serious and lead to transplant loss. The expertise of vascular surgeons finds its place here and makes it possible to maintain low rates of vascular complications and loss of transplants. PMID- 26995526 TI - Two novel phenanthraquinones with anti-cancer activity isolated from Bletilla striata. AB - 7-Hydroxy-2-methoxy-phenanthrene-3,4-dione and 3',7',7-trihydroxy-2,2',4' trimethoxy-[1,8'-biphenanthrene]-3,4-dione, two novel compounds and four known compounds were isolated from Bletilla striata. The structures of the compounds were established on the basis of extensive spectroscopic analysis. The two compounds exhibited antiproliferative effects using the MTT test; these effects may be due to cell cycle arrest and inducing ROS generation. PMID- 26995527 TI - Synthesis and antitumor activity of ATB-429 derivatives containing a nitric oxide releasing moiety. AB - A series of novel ATB-429 (an anti-inflammatory candidate) derivatives containing a nitric oxide (NO)-releasing moiety were designed, synthesized and evaluated for their in vitro activity against six human cancer cell lines. Our results reveal that phenylsulfonylfuroxan-based derivatives have considerable antitumor activity, and compounds 7-9 (IC50s: 0.256-3.024 MUM) against HT-29 and PANC-1, 8a,b (IC50s: 2.677-3.051 MUM) against MCF-7 and 8a (IC50: 1.270 MUM) against DU145 are more active than Vandetanib (IC50s: 1.925-4.107 MUM). PMID- 26995528 TI - Design, synthesis and structure activity relationship of potent pan-PIM kinase inhibitors derived from the pyridyl carboxamide scaffold. AB - The Pim proteins (1, 2 and 3) are serine/threonine kinases that have been found to be upregulated in many hematological malignancies and solid tumors. As a result of overlapping functions among the three isoforms, inhibition of all three Pim kinases has become an attractive strategy for cancer therapy. Herein we describe our efforts in identifying potent pan-PIM inhibitors that are derived from our previously reported pyridyl carboxamide scaffold as part of a medicinal chemistry strategy to address metabolic stability. PMID- 26995529 TI - 2-Phenylbenzofuran derivatives as butyrylcholinesterase inhibitors: Synthesis, biological activity and molecular modeling. AB - A series of 2-phenylbenzofurans compounds was designed, synthesized and evaluated as cholinesterase inhibitors. The biological assay experiments showed that most of the compounds displayed a clearly selective inhibition for butyrylcholinesterase (BChE), while a weak or no effect towards acetylcholinesterase (AChE) was detected. Among these benzofuran derivatives, compound 16 exhibited the highest BChE inhibition with an IC50 value of 30.3 MUM. This compound was found to be a mixed-type inhibitor as determined by kinetic analysis. Moreover, molecular dynamics simulations revealed that compound 16 binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE and it displayed the best interaction energy value, in agreement with our experimental data. PMID- 26995530 TI - Minimum structural requirements for cell membrane leakage-mediated anti-MRSA activity of macrocyclic bis(bibenzyl)s. AB - Macrocyclic bis(bibenzyl)-type phenolic natural products, found exclusively in bryophytes, exhibit potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Here, in order to identify the minimum essential structure for cell membrane leakage-mediated anti-MRSA activity of these compounds, we synthesized acyclic fragment structures and evaluated their anti-MRSA activity. The activities of all of the acyclic fragments tested exhibited similar characteristics to those of the macrocycles, i.e., anti-MRSA bactericidal activity, an enhancing effect on influx and efflux of ethidium bromide (EtBr: fluorescent DNA-binder) in Staphylococcus aureus cells, and bactericidal activity towards a Staphylococcus aureus strain resistant to 2 phenoxyphenol (4). The latter result suggests that they have a different mechanism of action from 4, which is a FabI inhibitor previously proposed to be the minimum active fragment of riccardin-type macrocycles. Thus, cyclic structure is not a necessary condition for cell membrane leakage-mediated anti-MRSA activity of macrocyclic bis(bibenzyl)s. PMID- 26995531 TI - Development of a potent and selective FLT3 kinase inhibitor by systematic expansion of a non-selective fragment-screening hit. AB - A non-selective inhibitor (1) of FMS-like tyrosine kinase-3 (FLT3) was identified by fragment screening and systematically modified to afford a potent and selective inhibitor 26. We confirmed that 26 inhibited the growth of FLT-3 activated human acute myeloid leukemia cell line MV4-11. Our design strategy enabled rapid development of a novel type of FLT3 inhibitor from the hit fragment in the absence of target-structural information. PMID- 26995532 TI - Management of pancreatic trauma. AB - INTRODUCTION: Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated. MATERIAL AND METHODS: Retrospective study of PT treated in the University Hospital of Grenoble over a 22-year span. The decision for initial laparotomy depended on hemodynamic status as well as on associated lesions. Main pancreatic duct lesions were always searched for. PT lesions were graded according to the AAST classification. RESULTS: Of a total of 46 PT, 34 were grades II or I. Hemodynamic instability led to immediate laparotomy in 18 patients, for whom treatment was always drainage of the pancreatic bed; morbidity was 30%. Eight patients had grade III injuries, six of whom underwent immediate operation: three underwent splenopancreatectomy without any major complications while the other three who had simple drainage required re-operation for peritonitis, with one death related to pancreatic complications. Four patients had grades IV or V PT: two pancreatoduodenectomies were performed, with no major complication, while one patient underwent duodenal reconstruction with pancreatic drainage, complicated by pancreatic and duodenal fistula requiring a hospital stay of two months. The post-trauma course was complicated for all patients with main pancreatic duct involvement. Our outcomes were similar to those found in the literature. CONCLUSION: In patients with distal PT and main pancreatic duct involvement, simple drainage is associated with high morbidity and mortality. For proximal PT, the therapeutic options of drainage versus pancreatoduodenectomy must be weighed; pancreatoduodenectomy may be unavoidable when the duodenum is injured as well. Two-stage (resection first, reconstruction later) could be an effective alternative in the emergency setting when there are other associated traumatic lesions. PMID- 26995533 TI - Comparative proteomic analysis of extracellular secreted proteins expressed by two pathogenic Acanthamoeba castellanii clinical isolates and a non-pathogenic ATCC strain. AB - Acanthamoeba keratitis (AK) is a serious ocular disease caused by pathogenic Acanthamoeba gaining entry through wounds in the corneal injury; generally, patients at risk for contracting AK wear contact lenses, usually over a long period of time. Moreover, pathogenic Acanthamoeba causes serious consequences: it makes the cornea turbid and difficult to operate on, including procedures such as enucleation of the eyeball. At present, diagnosis of this disease is not straightforward, and treatment is very demanding. We have established the comparative transcriptome and extracellular secreted proteomic database according to the non-pathogenic strain ATCC 30010 and the pathogenic strains NCKU_B and NCKU_D. We identified 44 secreted proteins successfully, 10 consensus secreted proteins and 34 strain-specific secreted proteins. These proteins may provide targets for therapy and immuno-diagnosis of Acanthamoeba infections. This study shows a suitable approach to identify secreted proteins in Acanthamoeba and provides new perspectives for the study of molecules potentially involved in the AK. PMID- 26995534 TI - Larvicidal activity of extracts from Ammi visnaga Linn. (Apiaceae) seeds against Culex quinquefasciatus Say. (Diptera: Culicidae). AB - Efficacies of the Ammi visnaga seeds extract and a majority of substances on larval Culex quinquefasciatus mortality in various development stages including pupae were studied. The effect of exposure time on larval mortality was also studied. The effect of sublethal concentrations or short exposure times on further larval development and subsequent fecundity in adults were studied as well. Lethal doses of the extract were estimated for the 2nd, 3rd and 4th instar of C. quinquefasciatus (LC50 for 18, 23 and 180 mg L(-1), respectively). The majority of furanochromenes, khellin and visnagin, were identified by analysing the extract. Khellin was significantly more effective compared to visnagin, whose LC50 was estimated at 8, 10 and 41 mg L(-1) for the 2nd, 3rd and 4th instar larvae. Khellin showed very fast efficacy on mortality for the 3rd instar larvae in a concentration of 100 mg L(-1). Fifty percent mortality was determined 30 min after application, a time which was considerably shorter compared to the extract (113 min) or visnagin (169 min). The effect of the application of lethal concentrations on C. quinquefasciatus larval mortality was studied. The least number of adults were hatched after application of the extract and khellin (41.8% and 37.9%, respectively), less than after visnagin application (46.7%) or in the control (94.2%). LC50 application caused lower fecundity in the hatched adults, lower hatchability of the eggs, and also very low natality, more than 77% lower for khellin compared to the control. A short exposure, corresponding to our estimated LT30, caused no significant acute toxicity in the larvae (until 24 h) for the extract or visnagin (4.3% and 11.5%, respectively); however, 18 min of action from khellin caused a 54.3% mortality rate of the larvae within 24 h. PMID- 26995535 TI - Differential parasitological, molecular, and serological detection of Trypanosoma cruzi I, II, and IV in blood of experimentally infected mice. AB - Trypanosoma cruzi is the etiological agent of American trypanosomiasis (Chagas' disease), which affects 6-7 million people worldwide, mainly in Latin America. It presents great genetic and biological variability that plays an important role in the clinical and epidemiological features of the disease. Our working hypothesis is that the genetic diversity of T. cruzi has an important impact on detection of the parasite using diagnostic techniques. The present study evaluated the diagnostic performance of parasitological, molecular, and serological techniques for detecting 27 strains of T. cruzi that belonged to discrete typing units (DTUs) TcI (11 strains), TcII (four strains), and TcIV (12 strains) that were obtained from different hosts in the states of Amazonas and Parana, Brazil. Blood samples were taken from experimentally infected mice and analyzed by fresh blood examination, hemoculture in Liver Infusion Tryptose (LIT) medium, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). Polymerase chain reaction presented the best detection of TcI, with 80.4% positivity. For all of the detection methods, the animals that were inoculated with TcII presented the highest positivity rates (94.1-100%). ELISA that was performed 7 months after inoculation presented a higher detection ability (95.4%) for TcIV. Intra-DTU comparisons showed that the reproducibility of the majority of the results that were obtained with the different methods was weak for TcI and good for TcII and TcIV. Our data indicate that the detection capability of different techniques varies with the DTUs of the parasites in mammalian blood. The implications of these findings with regard to the diagnosis of human T. cruzi infection are discussed. PMID- 26995536 TI - Relation between iron metabolism and antioxidants enzymes and delta-ALA-D activity in rats experimentally infected by Fasciola hepatica. AB - The aim of this study was to evaluate the iron metabolism in serum, as well as antioxidant enzymes, in addition to the Delta-Aminolevulinic Acid Dehydratase (delta-ALA-D) activity in the liver of rats experimentally infected by Fasciola hepatica. Thirty male adult rats (Wistar) specific pathogen free were divided into four groups: two uninfected group (CTRL 1 and CTRL 2) with five animals each and two infected groups (INF 1 and INF 2) with 10 animals each. Infection was performed orally with 20 metacercariae at day 1. On day 15 (CTRL 1 and INF 1 groups) and 87 PI (CTRL 2 and INF 2 groups) blood and bone marrow were collected and the animals were subsequently euthanized for liver sampling. Blood was allocated in tubes without anticoagulant for serum acquisition to measure iron, transferrin and unsaturated iron binding capacity (UIBC). delta-ALA-D, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the liver. A decrease in iron, transferrin and UIBC levels was observed in all infected animals compared to control groups (P < 0.05). Furthermore, iron accumulation was observed in bone marrow of infected mice. Infected animals showed an increase in delta-ALA-D activity at 87 post-infection (PI) (INF 2) as well as in SOD activity at days 15 (INF 1) and 87 PI (INF 2). On the other hand, CAT activity was reduced in rats infected by F. hepatica during acute and chronic phase of fasciolosis (INF 1 and INF 2 groups), when moderate (acute) and severe necrosis in the liver histopathology were observed. These results may suggest that oxidative damage to tissues along with antioxidant mechanisms might have taken part in fasciolosis pathogenesis and are also involved in iron deficiency associated to changes in delta-ALA-D activity during chronic phase of disease. PMID- 26995537 TI - Is plasticity across seasons adaptive in the annual cleistogamous plant Lamium amplexicaule? AB - BACKGROUND AND AIMS: Many angiosperms exhibit cleistogamy, the production of both cleistogamous flowers (CL), which remain closed and obligately self-pollinated, and chasmogamous flowers (CH), which are potentially open-pollinated. The CH proportion can be plastic. Plasticity is adaptive if environmental changes can be reliably assessed and responded to with an appropriate phenotype and if plastic genotypes have higher fitness in variable environments than non-plastic ones. METHODS: We studied the plastic response of four natural populations from northern and southern France of an annual cleistogamous plant, Lamium amplexicaule, to predictable seasonal variation. Plants were grown in a semi controlled environment in spring and in autumn. We assessed the variation in flower number, phenology and cleistogamy-related traits, which were all plastic with respect to season. The CH proportion was higher in spring than in autumn in all four populations. KEY RESULTS: We showed significant stabilizing selection for cleistogamy traits, with higher optimal CH proportions and more pronounced stabilizing selection in spring than in autumn. Observed CH proportions were close to the predicted optimal CH proportions in each season except in autumn for southern populations, which do not experience the autumnal growing season in nature. CONCLUSIONS: These results are consistent with adaptive plasticity across seasons of cleistogamy in L. amplexicaule.We propose that adaptive plasticity of cleistogamy could be driven by pollination environment variation, with CL flowers providing reproductive assurance when pollinators are scarce and CH flowers reducing the inbreeding depression in offspring when pollinators are abundant. PMID- 26995538 TI - Stage Grouping. PMID- 26995539 TI - Testicular Torsion-Can We Improve the Management of Acute Scrotum? PMID- 26995540 TI - Blue Light Cystoscopy Should be Used Routinely for Bladder Cancer Detection: Con. PMID- 26995541 TI - Peer Review. PMID- 26995542 TI - Blue Light Cystoscopy Should be Used Routinely for Bladder Cancer Detection: Pro. PMID- 26995544 TI - From Bench to Bedside. PMID- 26995545 TI - NGWA News. PMID- 26995546 TI - Overview of Transgenic Glioblastoma and Oligoastrocytoma CNS Models and Their Utility in Drug Discovery. AB - Many animal models have been developed to investigate the sources of central nervous system (CNS) tumor heterogeneity. Reviewed in this unit is a recently developed CNS tumor model using the piggyBac transposon system delivered by in utero electroporation, in which sources of tumor heterogeneity can be conveniently studied. Their applications for studying CNS tumors and drug discovery are also reviewed. (c) 2016 by John Wiley & Sons, Inc. PMID- 26995548 TI - Methods of Inducing Inflammatory Bowel Disease in Mice. AB - Animal models of experimentally induced inflammatory bowel disease (IBD) are useful for understanding more about the mechanistic basis of the disease, identifying new targets for therapeutic intervention, and testing novel therapeutics. This unit provides detailed protocols for five widely used mouse models of experimentally induced intestinal inflammation: chemical induction of colitis by dextran sodium sulfate (DSS), hapten-induced colitis via 2,4,6 trinitrobenzene sulfonic acid (TNBS), Helicobacter-induced colitis in mdr1a(-/-) mice, the CD4(+) CD45RB(hi) SCID transfer colitis model, and the IL-10(-/-) colitis model. (c) 2016 by John Wiley & Sons, Inc. PMID- 26995549 TI - Models of Inflammation: Carrageenan Air Pouch. AB - The subcutaneous air pouch is an in vivo model that can be used to study the components of acute and chronic inflammation, the resolution of the inflammatory response, the oxidative stress response, and potential therapeutic targets for treating inflammation. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this unit has been extensively used to identify potential anti-inflammatory drugs. PMID- 26995547 TI - Overview of Genetically Engineered Mouse Models of Distinct Breast Cancer Subtypes. AB - Advances in the screening of new therapeutic options have significantly reduced the breast cancer death rate over the last decade. Despite these advances, breast cancer remains the second leading cause of cancer death among women. This is due in part to the complexity of the disease, which is characterized by multiple subtypes that are driven by different genetic mechanisms and that likely arise from different cell types of origin. Because these differences often drive treatment options and outcomes, it is important to select relevant preclinical model systems to study new therapeutic interventions and tumor biology. Described in this unit are the characteristics and applications of validated genetically engineered mouse models (GEMMs) of basal-like, luminal, and claudin-low human subtypes of breast cancer. These different subtypes have different clinical outcomes and require different treatment strategies. These GEMMs can be considered faithful surrogates of their human disease counterparts. They represent alternative preclinical tumor models to cell line and patient-derived xenografts for preclinical drug discovery and tumor biology studies. PMID- 26995550 TI - Drug Combinations: Tests and Analysis with Isoboles. AB - Described in this unit are experimental and computational methods to detect and classify drug interactions. In most cases, this relates to two drugs or compounds with overtly similar effects, e.g., two analgesics or two anti-hypertensives. From the dose-response data of the individual drugs, it is possible to generate a curve, the isobole, which defines all dose combinations that are expected to yield a specified effect. The theory underlying the isobole involves the calculation of doses of drug A that are effectively equivalent to doses of drug B with that equivalence determining whether the isobole is linear or nonlinear. In either case, the isobole allows for a comparison with actual combination effects making it possible to determine whether the interaction is synergistic, additive, or sub-additive. Actual as well as illustrative data are employed to demonstrate experimental design and data analysis. PMID- 26995551 TI - A new light on the meiotic DSB catalytic complex. AB - Meiotic recombination is initiated by the formation of programmed DNA double strand breaks (DSBs). More than 15 years ago, Spo11 was identified as the protein responsible for meiotic DSB formation, notably because of its striking similarities with the A subunit of topoisomerase VI (TopoVI). TopoVI are enzymes that modify DNA topology by generating transient DSBs and are active as heterotetramers, composed of two A and two B subunits. A2 dimers catalyse the DNA cleavage reaction, whereas the B subunits regulate A2 conformation, DNA capture, cleavage and re-ligation. The recent identification in plants and mammals of a B like TopoVI subunit that interacts with SPO11 and is required for meiotic DSB formation makes us to reconsider our understanding of the meiotic DSB catalytic complex. We provide here an overview of the knowledge on TopoVI structure and mode of action and we compare them with their meiotic counterparts. This allows us to discuss the nature, structure and functions of the meiotic TopoVI-like complex during meiotic DSB formation. PMID- 26995552 TI - Erratum to: Predictors of Physician Recommendation for Ethically Controversial Medical Procedures: Findings from an Exploratory National Survey of American Muslim Physicians. PMID- 26995553 TI - Early cranioplasty: There is still much to be uncovered. PMID- 26995554 TI - Facile sonochemical synthesis of nanostructured NiO with different particle sizes and its electrochemical properties for supercapacitor application. AB - In this work, we demonstrate the influence of nickel oxides with divergent particle sizes as the working electrodes for supercapacitor application. The nanostructured nickel oxide (NiO) is synthesized via facile sonochemical method, followed by calcination process. The crystallinity and surface purity of prepared samples are clearly examined by X-ray diffraction and Raman analysis. NiO crystallinity is significantly increased with increasing calcination temperatures. The surface analysis confirmed that the calcination at 250 degrees C exhibited nanoclutser like NiO with average particle size of ~6nm. While increasing the calcination temperature beyond 250 degrees C, hexagonal shaped NiO is observed with enhanced particle sizes. The electrochemical performance confirmed the good redox behavior of NiO electrodes. Moreover, NiO with average particle size of ~6nm exhibited high specific capacitance of 449F/g at a scan rate of 5mV/s compared to other samples with particle sizes of ~21nm (323F/g) and ~41nm (63F/g). This is due to the good ion transfer mechanism and effective electrochemical utilization of the working electrode. PMID- 26995555 TI - Reversible structural and functional changes after intraocular pressure reduction in patients with glaucoma. AB - PURPOSE: The aim of this study was to evaluate structural and functional improvement following intraocular pressure (IOP) reduction in patients with glaucoma using Spectral Domain Optical Coherence Tomography (SD-OCT), Visual Field (VF) testing, and Visual Evoked Potentials (VEP). METHODS: A total of 76 eyes from 61 patients underwent SD-OCT, VF and VEP testing. Sixty-two eyes were put in either an acutely high (group 1, IOP > 32 mmHg) or mildly high (group 2, IOP between 22 and 31 mmHg) IOP group and underwent a pressure-lowering intervention. Fourteen eyes with stable glaucoma were controls (group 3, IOP < 22 mmHg). SD-OCT, VF and VEP testing were subsequently performed on all patients at three follow-up visits. Results from these follow-up periods were analyzed for signs of functional and structural improvement. RESULTS: Both group 1 and group 2 patients demonstrated significant decrease in the average cup to disc ratio (p < 0.05) following the intervention. Post-interventional reduction of cup volume was also significant for group 2 patients (p < 0.05). RNFL thickness changes were insignificant. Qualitative grading of VFs by two observers showed improvement in group 1 patients' VFs (p = 0.021). VEP measurements were mostly insignificant, with the exception of High Contrast Latency (LHC) deteriorating for group 2 patients in the first follow-up visit (p = 0.025). CONCLUSIONS: This study provides evidence for structural disc cupping reversal following IOP lowering interventions. These changes were not related to the amount of pressure lowering. While there was evidence of functional improvement as measured by VF testing, VEP was unable to detect any reversible changes. PMID- 26995557 TI - Robust inference from multiple test statistics via permutations: a better alternative to the single test statistics approach for randomized trials. PMID- 26995556 TI - Evaluation of nailfold videocapillaroscopy in central serous chorioretinopathy. AB - BACKGROUND: Nailfold videocapillaroscopy (NVC) is a diagnostic tool to evaluate micro-vasculature. The presence of choroidal vasculopathy is apparent in central serous chorioretinopathy (CSCR). OBJECTIVES: This study was aimed at assessing capillaroscopic nailfold findings in patients with CSCR. To the best of our knowledge, there is no study assessing NVC findings in CSCR in the literature. METHOD: Sixty-one patients with CSCR who met the inclusion criteria, and 82 age- and sex-matched healthy controls were included to the study. A videocapillaroscopy device with 200* magnification was used for capillaroscopic assessment. RESULTS: The mean age was 48.79 +/- 11.15 years in the patient group (13 female, 48 male) and 49.38 +/- 9.02 years in the control group (17 female, 65 male). The age and gender were comparable in the patient and control groups (p = 0.727 and p = 0.933, respectively). The capillary count was found to be decreased in the patient group compared to control group. No significant correlation was found between capillary count and choroidal thickness (p = 0.551; r = -0.081). In the patient group, the frequencies of major capillaroscopic findings including capillary ectasia, aneurysm, micro-hemorrhage, avascular area, tortuosity, neo formation, bizarre capillary, bushy capillary, meander capillary and extravasation were found to be increased in the patient group. However, no significant correlation was detected between capillaroscopic findings and disease type and presence of attacks. CONCLUSIONS: This is first study in which nailfold capillary assessment was performed in patients with CSCR, and we detected major capillaroscopic changes. These findings suggest that CSCR can be a systemic microvasculopathy. Further studies are needed to clarify the diagnostic and prognostic value of capillaroscopy in CSCR. PMID- 26995559 TI - Erratum to: Distilling the essence of appraisal: a mixed methods study of people with multiple sclerosis. PMID- 26995558 TI - Investigation of Neurokinin-1 Receptor Antagonism as a Novel Treatment for Chronic Bronchitis in Dogs. AB - BACKGROUND: Canine chronic bronchitis (CCB) results in cough lasting >=2 months and airway inflammation. Adverse effects include risk of secondary infection associated with lifelong corticosteroid administration and prompt investigation into alternative therapies. Neurogenic pathways mediated by tachykinins that bind neurokinin (NK) 1 receptors may induce cough and airway inflammation. Maropitant, a NK-1 receptor antagonist, has been advocated for treatment of CCB based on anecdotal improvement, but without scientific evidence. HYPOTHESIS/OBJECTIVES: Maropitant will blunt clinical signs and airway inflammation associated with CCB. ANIMALS: Client-owned dogs (n = 8) with cough >2 months, thoracic radiographic evidence of airway disease and sterile airway inflammation (>7% non-degenerate neutrophils, >7% eosinophils or both) on bronchoalveolar lavage (BAL) enrolled. METHODS: Maropitant (2 mg/kg) administered q48h for 14 days. Study endpoints included client perception of clinical signs (surveys at baseline and 14 days, and visual analogue scale [VAS] at baseline, 7, and 14 days), and BAL % neutrophils and eosinophils (baseline and 14 days). One-way repeated measures ANOVA (VAS) and Wilcoxon-signed rank-sum tests (BAL cells, cough frequency) used with P < .05 considered significant. RESULTS: Maropitant significantly decreased cough frequency (P < .001) and VAS scores (P = .005). No differences in BAL % neutrophils or % eosinophils noted with treatment (P = .279 and P = .382, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Preliminary results suggest that although maropitant may have antitussive properties leading to perceived clinical improvement, its failure to diminish airway inflammation makes it unsuitable for treatment of CCB. Future studies could evaluate maropitant as a cough suppressant for other respiratory disorders in dogs. PMID- 26995560 TI - Perceived quality of life, 6 months after detoxification: Is abstinence a modifying factor? AB - PURPOSE: Patients with a substance use disorder (SUD), admitted for detoxification, often suffer from a poor quality of life (QoL). We set out to monitor QoL, together with substance use, in a departure from the usual norm of measuring substance use alone as a treatment outcome. Literature searches revealed scant knowledge of how QoL is influenced. With this in mind, we aimed to investigate whether total abstinence, prior to follow-up, could influence QoL. METHODS: We studied a prospective cohort of 140 patients admitted for inpatient detoxification treatment at Sorlandet Hospital (Norway), from September 2008 to August 2010. QoL was measured by a generic five-item questionnaire, the QoL-5. The extremes of this scale ranged from the worst possible rating of 0.1 to 0.9, as the best. A norm for the general population was benchmarked at 0.69. Change in QoL was calculated by subtracting baseline QoL from that achieved at the 6-month follow-up interview; linear regression modeling was used to study the influence of individual QoL predictors. RESULTS: The mean QoL at baseline was 0.46, 39 % below that of the general reference population. By applying the clinical interpretation of the scale, we found a modest overall mean improvement in QoL at follow-up (0.11 points); the greatest increases were seen for patients with the lowest baseline QoL scores. Abstinence prior to follow-up correlated with improved QoL, while living alone and psychological distress were negative influences. CONCLUSIONS: For patients with a SUD, clinicians should emphasize that abstinence may help to improve their QoL. PMID- 26995561 TI - Quantifying clinical change: discrepancies between patients' and providers' perspectives. AB - PURPOSE: Interpreting the clinical significance of changes in patient-reported outcomes (PROs) is critically important. The most commonly used approach is to anchor mean changes on PRO scores against a global assessment of change. Whether the assessor of global change should be patients or their physicians is unknown. We compared patients' and physicians' assessments of change over time to examine which was more aligned with patients' changes in PRO measures. METHODS: A total of 459 chronic heart failure patients aged >30 years were enrolled from 13 US centers. Data were obtained by medical record abstraction, physical assessments, and patient interviews at a baseline clinic visit and 6 weeks later. Health status was measured with the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ), and both patients and physicians completed a validated 15 level global assessment of change, ranging from large deterioration to large improvement. RESULTS: There was substantial variation between physicians/patients' global assessment of clinical change (weighted kappa = 0.36, 95 % CI 0.28, 0.43). Overall, physician assessments were more strongly correlated with change on the KCCQ summary score than were patients' assessments (physician R = 0.37, patient R = 0.29). CONCLUSION: There was substantial variation between patients' and physicians' global assessment of 6-week change in heart failure status. Physician assessments of the importance of clinical changes were more strongly associated with changes in all domains of patient-reported health status, as assessed by the KCCQ, and may provide a more consistent method for defining the clinical importance of changes in patients' health status. PMID- 26995562 TI - The Guttman errors as a tool for response shift detection at subgroup and item levels. AB - PURPOSE: Statistical methods for identifying response shift (RS) at the individual level could be of great practical value in interpreting change in PRO data. Guttman errors (GE) may help to identify discrepancies in respondent's answers to items compared to an expected response pattern and to identify subgroups of patients that are more likely to present response shift. This study explores the benefits of using a GE-based method for RS detection at the subgroup and item levels. METHODS: The analysis was performed on the SatisQoL study. The number of GE was determined for each individual at each time of measurement (at baseline T0 and 6 months after discharge M6). Individuals showing discrepancies (with many GE) were suspected to interpret the items differently from the majority of the sample. Patients having a large number of GE at M6 only and not at T0 were assumed to present RS. Patients having a small number of GE at T0 and M6 were assumed to present no RS. The RespOnse Shift ALgorithm in Item response theory (ROSALI) was then applied on the whole sample and on both groups. RESULTS: Different types of RS (non-uniform recalibration, reprioritization) were more prevalent in the group composed of patients assumed to present RS based on GE. On the opposite, no RS was detected on patients having few GE. CONCLUSIONS: Guttman errors and item response theory models seem to be relevant tools to discriminate individuals affected by RS from the others at the item level. PMID- 26995564 TI - Describing the evolution of mobile technology usage for Latino patients and comparing findings to national mHealth estimates. AB - OBJECTIVES: Describe the change in mobile technology used by an urban Latino population between 2011 and 2014, and compare findings with national estimates. MATERIALS AND METHODS: Patients were surveyed on medical history and mobile technology use. We analyzed specific areas of mobile health capacity stratified by chronic disease, age, language preference, and educational attainment. RESULTS: Of 2144 Latino patients, the percentage that owned a cell phone and texted were in-line with Pew estimates, but app usage was not. Patients with chronic disease had reduced access to mobile devices (P < .001) and lower use of mobile phone functionalities. DISCUSSION: Prior research suggests that Latinos can access mHealth; however, we observed lower rates among Latino patients actively seeking heath care. CONCLUSION: Published national estimates do not accurately reflect the mobile technology use of Latino patients served by our public safety-net facility. The difference is greater for older, less educated patients with chronic disease. PMID- 26995565 TI - Quantitative trait loci for a neurocranium deformity, lack of operculum, in gilthead seabream (Sparus aurata L.). AB - Lack of operculum, a neurocranial deformity, is the most common external abnormality to be found among industrially produced gilthead seabream (Sparus aurata L.), and this entails significant financial losses. This study conducts, for the first time in this species, a quantitative trait loci (QTL) analysis of the lack of operculum. A total of 142 individuals from a paternal half-sibling family (six full-sibling families) were selected for QTL mapping. They had previously shown a highly significant association with the prevalence of lack of operculum in a segregation analysis. All the fish were genotyped for 106 microsatellite markers using a set of multiplex PCRs (ReMsa1-ReMsa13). A linear regression methodology was used for the QTL analysis. Four QTL were detected for this deformity, two of which (QTLOP1 and QTLOP2) were significant. They were located at LG (linkage group) nine and LG10 respectively. Both QTL showed a large effect (about 27%), and furthermore, the association between lack of operculum and sire allelic segregation observed was statistically significant in the QTLOP1 analysis. These results represent a significant step towards including marker assisted selection for this deformity in genetic breeding programmes to reduce the incidence of the deformity in the species. PMID- 26995563 TI - Quality of life of individuals born preterm: a systematic review of assessment approaches. AB - PURPOSE: To review the existing literature regarding factors associated with quality of life (QoL) of individuals who were born preterm. The review focuses on assessment approaches and information sources. METHODS: A systematic review of empirical studies published in PubMed, PsycARTICLES, PsycINFO, LILACS, and SciELO databases between 2007 and 2015. Search terms were chosen that relate preterm birth to QoL. RESULTS: Twenty-two articles were included. Of these, ten investigated QoL in children, six investigated adolescents, and six investigated adults. All studies used generic instruments to assess QoL. There was a high rate of parental report to assess QoL in studies of children. Adolescent and adult studies most often assessed QoL through self-report. Parents of children who were born preterm reported worse QoL for their children compared with parents of children born full term. Teenagers and adults who were born preterm self-reported more positive outcomes in their QoL. The main risk factors associated with worse QoL in children who were born preterm were congenital malformations, mechanical ventilation during the neonatal phase, cognitive impairments, behavioral problems, physical disabilities, low family income, and black race. CONCLUSIONS: Agreement between parents and children about QoL in preterm individuals was lower in younger age groups compared with older age groups. The differences in QoL throughout the different age groups may have arisen because of developmental changes or differences in the source of information used (i.e., parent report or self-report). We recommend that QoL assessments in children born preterm should consider both parent report and self-report. PMID- 26995566 TI - Polymorphisms in PEG10 and PPP1R9A genes are associated with porcine carcass and meat quality traits. PMID- 26995568 TI - Assessment of postpartum symphysis pubis distention with 3D ultrasonography: a novel method. AB - OBJECTIVES: Determining the accuracy of three-dimensional (3D) sonographic measurement of symphysis pubis (SP) distension in comparison to plain X-ray pelvic radiographs and assessing the interperformer reliability of this method. METHODS: Pelvic X-ray was performed on 86 women who delivered singleton babies within 36 h of delivery then each woman was examined by 3D transperineal ultrasound imaging by two sonogrographers. RESULTS: Measurements of SP with 3D transperineal ultrasonography in comparison to pelvic X-ray showed 95% limits of agreement. Interperformer reproducibility was substantial (interclass correlation coefficient 0.66-0.70) for measures of SP. CONCLUSIONS: Pubic symphysis width, superior pubic ligament length, and SP height can be reliably measured with 3D ultrasonography. PMID- 26995567 TI - Geography matters: state-level variation in children's oral health care access and oral health status. AB - OBJECTIVES: To ascertain differences across states in children's oral health care access and oral health status and the factors that contribute to those differences. STUDY DESIGN: Observational study using cross-sectional surveys. METHODS: Using the 2007 National Survey of Children's Health, we examined state variation in parents' report of children's oral health care access (absence of a preventive dental visit) and oral health status. We assessed the unadjusted prevalences of these outcomes, then adjusted with child-, family-, and neighbourhood-level variables using logistic regression; these results are presented directly and graphically. Using multilevel analysis, we then calculated the degree to which child-, family-, and community-level variables explained state variation. Finally, we quantified the influence of state-level variables on state variation. RESULTS: Unadjusted rates of no preventive dental care ranged 9.0-26.8% (mean 17.5%), with little impact of adjusting (10.3-26.7%). Almost 9% of the population had fair/poor oral health; unadjusted range 4.1-14.5%. Adjusting analyses affected fair/poor oral health more than access (5.7-10.7%). Child, family and community factors explained ~1/4 of the state variation in no preventive visit and ~1/2 of fair/poor oral health. State-level factors further contributed to explaining up to a third of residual state variation. CONCLUSION: Geography matters: where a child lives has a large impact on his or her access to oral health care and oral health status, even after adjusting for child, family, community, and state variables. As state-level variation persists, other factors and richer data are needed to clarify the variation and drive changes for more egalitarian and overall improved oral health. PMID- 26995569 TI - Proximal thoracic aortic diameters: transesophageal-echocardiography- versus computed-tomography-derived measurements. AB - PURPOSE: The purpose of the study was to compare proximal aortic measurements from electrocardiogram-gated computed tomography (CT) to transesophageal echocardiography (TEE) and to evaluate differences in cusp-cusp and cusp commissure CT measurements of sinus of Valsalva (SOV). METHODS: This retrospective study (n=25) compared aortic diameters from CT using manual double oblique multiplanar reformats (MPRs) and semiautomatic centerline method to TEE. RESULTS: CT MPR and centerline measurements were higher than TEE for sinotubular junction and ascending aorta. At SOV, cusp-cusp diameters (MPR and centerline methods) and cusp-commissure measurement (centerline method) were larger than TEE. CONCLUSIONS: Aortic measurements were larger on CT than TEE. Precise difference depended on location and measurement technique. PMID- 26995572 TI - Arterial phase CT for the detection of splenic injuries in blunt trauma: would it improve clinical outcomes? AB - OBJECTIVE: To determine if the addition of an arterial phase abdominal computed tomography (CT) improves clinical outcomes in patients with blunt splenic injuries. METHODS: Retrospective review of patients who underwent CT of the abdomen revealing splenic injuries. Clinical management in these patients was determined. RESULTS: Fifty-one of three thousand five hundred twenty-five patients had splenic injuries. Twenty-five patients underwent nonsurgical management, and 3 failed. The theoretical additional arterial phase resulted in a 62% increase in mean effective dose compared to the portal venous phase alone. CONCLUSIONS: Routine use of arterial phase CT in blunt trauma patients may not be warranted as there is minimal improvement in outcomes. PMID- 26995571 TI - Comparison of image quality, and diagnostic interpretability of a new volumetric high temporal resolution scanner versus 64-slice MDCT. AB - We evaluated the performance of a new volume computed tomographic (CT) scanner with regards to image quality and signal homogeneity. Twenty-four subjects were prospectively enrolled. Subjects had prior imaging with rate control. Quantitative analyses performed placing regions of interest in myocardium, blood pool, and aorta. Image quality and diagnostic interpretability were assessed using Likert scales. Median heart rate was 60 and 57 bpm for volume and 64-slice coronary CT angiography (P=.02). Improvement in homogeneity was demonstrated within myocardium (30% improvement), blood pool (73%), and aorta (73%). Improvement in image quality observed at per-patient/per-segment level. Pilot study confirmed improvements in signal homogeneity and diagnostic interpretability, despite imaging at higher heart rates. PMID- 26995570 TI - A history of breast cancer and older age allow risk stratification of mammographic BI-RADS 3 ratings in the diagnostic setting. AB - OBJECTIVE: The objective was to investigate whether risk stratification of mammographic Breast Imaging: Reporting and Data System (BI-RADS) 3 can be accomplished in the diagnostic setting. METHODS: We analyzed 4941 BI-RADS-3-rated patients (23 malignant outcomes) and built logistic-regression models with age, personal and family history of breast cancer, fibroglandular density, and additional mammographic findings as predictive variables. RESULTS: A personal history of breast cancer (odds ratio: 5.53) and older age (odds ratio: 12.44/10.93 for age 50-64/>64) are independent risk factors. Patients with both risk factors have a risk >2%. CONCLUSION: Biopsy may be warranted in older patients with a history of breast cancer who would be otherwise assigned BI-RADS 3. PMID- 26995573 TI - Impact of a motion correction algorithm on quality and diagnostic utility in unselected patients undergoing coronary CT angiography. AB - AIMS: The aims of the study were to investigate the diagnostic utility of motion correction reconstruction algorithm Snapshot Freeze (SSF) compared to the standard reconstruction algorithm (STD) in coronary computed tomography angiography (CCTA) images where a prescan heart-rate-lowering protocol is fully integrated. METHODS: CCTA was performed in 140 patients. Two independent blinded readers made image evaluation of the SSF and STD images. RESULTS: SSF reduced the motion artifacts (30% vs. 41%; P<.05) and improved the image quality ("excellent" images: 52% vs. 42%; P=.022), but did not influence diagnostic utility ("nondiagnostic" images: 10% vs. 14%; P=.104). CONCLUSION: The use of the SSF algorithm reduced the presence of motion artifacts and improved image quality, but did not influence the diagnostic utility. PMID- 26995574 TI - MRI findings in eastern equine encephalitis: the "parenthesis" sign. AB - Two patients with eastern equine encephalitis (EEE) presented to a tertiary referral center. Both subjects' brain magnetic resonance imaging showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities including linear areas of hyperintensity in the external and internal capsules with sparing of the lentiform nuclei. Single case reports of imaging findings in EEE exist with nonspecific patterns of abnormality. We propose that this "( ) parentheses sign" on T2 or FLAIR imaging may distinguish EEE from other processes. PMID- 26995575 TI - Successful management of four unusual cases of acute aortic thrombus induced by chemotherapy. AB - An acute aortic thrombus is an unusual finding, and this is a source of distal arterial embolism, which has a poor prognosis. Chemotherapeutics have been reported as possible rare causes of acute arterial thrombus. We report four cases of acute aortic thrombus after chemotherapy, which were effectively treated with systemic anticoagulation or endovascular management. PMID- 26995577 TI - Ectopic craniopharyngioma of the fourth ventricle in a patient with Gardner syndrome. AB - Ectopic craniopharyngioma is uncommon and a craniopharyngioma confined purely within the fourth ventricle is extremely rare. We report a craniopharyngioma of the fourth ventricle in a 20-year-old man with Gardner syndrome. Imaging characteristics of craniopharyngiomas and fourth ventricle lesions are discussed with a review of the literature regarding the pathogenesis of craniopharyngiomas and the possible association with Gardner syndrome. PMID- 26995576 TI - Pancreatic neuroendocrine tumor with aneurysms of the gastroduodenal artery: a case report. AB - Gastroduodenal artery (GDA) aneurysm is a very rare condition. It is divided into false aneurysms (pseudoaneurysms) associated with pancreatitis and true aneurysms secondary to celiac trunk stenosis. We report a 24-year-old patient who was diagnosed with pancreatic head neuroendocrine tumor and was incidentally found to have multiple GDA aneurysms in the absence of celiac artery stenosis. The aneurysms were embolized because of the presumed high risk of bleeding. The procedure was successful with no recurrence on follow-up computed tomography scan. PMID- 26995578 TI - PHACE syndrome and congenitally absent thyroid gland at MR imaging. AB - PHACE syndrome is a rare neurocutaneous disorder characterized by posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, and abnormalities of the eye. Thyroid disorders associated with PHACE syndrome have been described, although there are limited reports of this rare occurrence. We report a case of PHACE syndrome with congenital hypothyroidism in an infant, for which absent thyroid gland was diagnosed at magnetic resonance imaging. PMID- 26995579 TI - MRI findings of subchondroplasty of the knee: a two-case report. AB - Bone marrow lesions observed in magnetic resonance imaging (MRI) have been recognized as a source of knee pain. Subchondroplasty was developed to treat these lesions with a percutaneous injection of calcium phosphate bone substitute into the bone. As subchondroplasty may potentially become a more common procedure in the treatment of knee osteoarthritis, it is important for radiologists to recognize the typical MRI findings and not to confuse them with other pathology. Here we report the MRI findings for two patients following subchondroplasty. PMID- 26995580 TI - Complete gastric duplication in an adult with associated anomalies. AB - Gastric duplication is a rare congenital developmental abnormality usually encountered in children. Nearly all reported cases of this entity describe noncommunicating-type duplication cysts. We present an extremely rare case of complete gastric duplication, involving two separate gastric lumens with proximal and distal communication, incidentally discovered in an elderly male in association with various congenital anomalies not previously reported in literature, as diagnosed with computed tomographic scan and upper gastrointestinal endoscopy. PMID- 26995581 TI - Multiple unilateral tarsal coalitions in a nonsyndromic patient. AB - Tarsal coalition is relatively frequent, with an estimated prevalence of 1-2%. Coalitions are most commonly talocalcaneal or calcaneonavicular, accounting for 90% of cases. While it is well known that bilateral tarsal coalitions can occur in up to 50% of cases, the presence of multiple coalitions in the same foot is less well described. In this report, we present a case of talocalcaneal and calcaneonavicular coalitions occurring in the same foot and briefly review the relevant literature. PMID- 26995582 TI - CT findings of human Fasciola hepatica infection: case reports and review of the literature. AB - Due to increasing rates of international travel, hepatic fascioliasis is appearing in nonendemic areas, where diagnosis can be difficult. We present two confirmed cases of hepatic fascioliasis in a nonendemic region. The purposes of this report are to discuss computed tomography (CT) findings of hepatic fascioliasis and to review the literature. While travel history is most important, characteristic findings of hypoattenuating tracts extending from liver capsule into the parenchyma on contrast-enhanced CT scan strongly suggest hepatic fascioliasis. PMID- 26995583 TI - Diagnosis and management of mycotic aneurysms. AB - Mycotic aneurysm (MA) is a focal dilation of an infected arterial wall. This uncommon disease follows an aggressive, unpredictable clinical course with significant mortality and presents unique diagnostic and therapeutic challenges. This review discusses the pathogenesis and the diagnostic challenges of MA. PMID- 26995584 TI - MR anatomy and pathology of the ulnar nerve involving the cubital tunnel and Guyon's canal. AB - Ulnar neuropathy is a common and frequent reason for referral to hand surgeons. Ulnar neuropathy mostly occurs in the cubital tunnel of the elbow or Guyon's canal of the wrist, and it is important for radiologists to understand the imaging anatomy at these common sites of impingement. We will review the imaging and anatomy of the ulnar nerve at the elbow and wrist, and we will present magnetic resonance imaging examples of different causes of ulnar neuropathy, including trauma, overuse, arthritis, masses and mass-like lesions, and systemic diseases. Treatment options will also be briefly discussed. PMID- 26995588 TI - Impact of a novel teaching method based on feedback, activity, individuality and relevance on students' learning. AB - OBJECTIVE: This study examines the perceived impact of a novel clinical teaching method based on FAIR principles (feedback, activity, individuality and relevance) on students' learning on clinical placement. METHODS: This was a qualitative research study. Participants were third year and final year medical students attached to one UK vascular firm over a four-year period (N=108). Students were asked to write a reflective essay on how FAIRness approach differs from previous clinical placement, and its advantages and disadvantages. Essays were thematically analysed and globally rated (positive, negative or neutral) by two independent researchers. RESULTS: Over 90% of essays reported positive experiences of feedback, activity, individuality and relevance model. The model provided multifaceted feedback; active participation; longitudinal improvement; relevance to stage of learning and future goals; structured teaching; professional development; safe learning environment; consultant involvement in teaching. Students perceived preparation for tutorials to be time intensive for tutors/students; a lack of teaching on medical sciences and direct observation of performance; more than once weekly sessions would be beneficial; some issues with peer and public feedback, relevance to upcoming exam and large group sizes. Students described negative experiences of "standard" clinical teaching. CONCLUSIONS: Progressive teaching programmes based on the FAIRness principles, feedback, activity, individuality and relevance, could be used as a model to improve current undergraduate clinical teaching. PMID- 26995589 TI - A novel metalloproteinase virulence factor is involved in Bacillus thuringiensis pathogenesis in nematodes and insects. AB - The Gram-positive soil bacterium Bacillus thuringiensis has been developed as the leading microbial insecticide for years. The pathogenesis of B. thuringiensis requires common extracellular factors that depend on the PlcR regulon, which regulates a large number of virulence factors; however, the precise role of many of these proteins is not known. In this study, we describe the complete lifecycle of a nematicidal B. thuringiensis strain in the free living nematode Caenorhabditis elegans using in vitro and in vivo molecular techniques to follow host and bacterial effectors during the infection process. We then focus on the metalloproteinase ColB, a collagenase, which was found highly important for destruction of the intestine thereby facilitates the adaptation and colonization of B. thuringiensis in C. elegans. In vivo green fluorescent protein (GFP) reporter-gene studies showed that ColB expression is highly induced and regulated by the global activator PlcR. Finally, we demonstrated that ColB also takes part in B. thuringiensis virulence in an insect model following injection and oral infection. Indeed, addition of purified ColB accelerates the action of Cry toxin proteins in insects, too. These results give novel insights into host adaptation for B. thuringiensis and other B. cereus group bacteria and highlight the role of collagenase metalloproteases to synergize infection process. PMID- 26995593 TI - Minimizing variance in pediatric gastrostomy: does standardized perioperative feeding plan decrease cost and improve outcomes? AB - BACKGROUND: A protocol for laparoscopic gastrostomy placement was implemented which specified perioperative antibiotics, feeding regimens, and discharge criteria. Our hypothesis was that hospital cost could be decreased, whereas at the same time improving or maintaining patient outcomes. METHODS: Data were collected on consecutive patients beginning 6 months after implementation of our protocol. We recorded surgeon compliance, patient outcomes (as defined by 30-day NSQIP complication rates), and cost of initial hospitalization, which was then compare to a 6-month historical control period. RESULTS: Our control group n = 26 and protocol group n = 39. Length of stay was shorter in the protocol group (P <= .05 by nonparametric analysis). The complication rate was similar in both groups (23% control vs 15% protocol, P = .43). Initial hospital costs were not different. Surgeon compliance to protocol was 82%. CONCLUSIONS: A standard protocol is achievable for gastrostomy tube management. After implementation of our protocol, we were able to show a significant decrease in length of stay, whereas maintaining quality. PMID- 26995592 TI - Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology. AB - Acute right ventricular (RV) failure is a complex clinical syndrome that results from many causes. Research efforts have disproportionately focused on the failing left ventricle, but recently the need has been recognized to achieve a more comprehensive understanding of RV anatomy, physiology, and pathophysiology, and of management approaches. Right ventricular mechanics and function are altered in the setting of either pressure overload or volume overload. Failure may also result from a primary reduction of myocardial contractility owing to ischaemia, cardiomyopathy, or arrhythmia. Dysfunction leads to impaired RV filling and increased right atrial pressures. As dysfunction progresses to overt RV failure, the RV chamber becomes more spherical and tricuspid regurgitation is aggravated, a cascade leading to increasing venous congestion. Ventricular interdependence results in impaired left ventricular filling, a decrease in left ventricular stroke volume, and ultimately low cardiac output and cardiogenic shock. Identification and treatment of the underlying cause of RV failure, such as acute pulmonary embolism, acute respiratory distress syndrome, acute decompensation of chronic pulmonary hypertension, RV infarction, or arrhythmia, is the primary management strategy. Judicious fluid management, use of inotropes and vasopressors, assist devices, and a strategy focusing on RV protection for mechanical ventilation if required all play a role in the clinical care of these patients. Future research should aim to address the remaining areas of uncertainty which result from the complexity of RV haemodynamics and lack of conclusive evidence regarding RV-specific treatment approaches. PMID- 26995594 TI - Axillary web syndrome: an underappreciated complication of sentinel node biopsy in melanoma. AB - OBJECTIVE: Axillary web syndrome (AWS) is known to occur after axillary dissection and has been reported after axillary sentinel lymph node biopsy (ASLNB) for breast cancer. However, the incidence and outcomes of AWS after ASLNB for melanoma are unknown. METHODS: A retrospective review of prospectively collected, clinically node-negative patients undergoing ASLNB for melanoma at a single institution during a 14-year period was conducted to determine the incidence of AWS. Features pertaining to patients (age and gender), primary tumor (location, Breslow's depth), and nodes (number removed, positive node rate) were correlated with the occurrence of AWS. RESULTS: Of the 465 patients undergoing ASLNB, 21 (4.5%) developed AWS postoperatively. In comparison, the incidence of other complications in this population were infection 3%, bleeding 1.5%, wound dehiscence .8%, lymphocele 5%, and lymphedema .4%. There was no statistical difference between patients with or without AWS in terms of tumor thickness, location of primary (upper extremity vs trunk), average number of sentinel nodes removed, positive SLNB rates (10% vs 12%), patient age, or gender. All cases of AWS resolved with expectant management; none required surgical intervention. CONCLUSIONS: AWS is a notable complication of ASLNB for melanoma, with an incidence as high or higher than "standard" complications. AWS should, therefore, be included in the preoperative discussion of possible complications of ASLNB. Traditional patient, tumor, and nodal factors are not predictive of AWS. Patients should be counseled that AWS usually responds to symptomatic treatment and resolves with time. PMID- 26995595 TI - Is There a Best Initial Treatment for a New Patient With Low Grade Follicular Lymphoma. AB - The treatment landscape for newly diagnosed follicular lymphoma (FL) has dramatically changed over the past decade, first with the advent of rituximab and then with the activity of old and new drugs, like bendamustine and lenalidomide, in this disease. The efficacy and tolerability of rituximab has led to a paradigm shift for the management of patients with low volume FL for many oncologists. Despite the lack of a survival benefit seen with this approach, many now use this single agent in patients who had historically been observed. Likewise, its use as maintenance therapy following successful front-line induction therapy of patients with symptomatic FL, with either rituximab alone or specific chemoimmunotherapy regimens, has improved remission duration and widely been adopted. As newer chemoimmunotherapy regimens, like bendamustine and rituximab, have superior outcomes with improved tolerability, upfront treatment options are redefined and questions emerge: whom do maintenance strategies benefit, and what is the optimal sequencing of therapies? Finally, as newer targeted and potentially better tolerated therapies demonstrate efficacy in the relapsed setting, their use, both in combination with and in place of chemotherapy, is being explored. The promising regimen of lenalidomide with rituximab is being compared with chemoimmunotherapy in a randomized fashion. Cure remains elusive, however, in advanced stage disease and so safety and tolerability, in addition to efficacy, remain important endpoints. PMID- 26995596 TI - Visualization, measurement and modelling of the cochlea using rotating midmodiolar slice planes. AB - PURPOSE: Cross-sectional visualization of anatomical structures in DICOM viewers is usually presented in parallel slices. For visualizing the inner ear, this concept is unfavourable due to the spiral shape of the cochlea. Radial slicing through its central axis (known as midmodiolar view) is advantageous. Therefore, a custom DICOM viewer was developed, which allows the visualization of the cochlea in a midmodiolar slice plane that rotates around the central axis of the cochlea, always cutting the latter radially. METHODS: The program was written in C++ using the open-source libraries ITK, VTK, GDCM and Qt. The rotation axis is defined by placing two points in the modiolus within a conventional slice visualization of the dataset. A midmodiolar visualization is calculated based on this axis. Scrolling the mouse wheel rotates slice plane around the axis, displaying midmodiolar slices at variable angles. Measurement options are provided as well as interactive placement of marker points whose coordinates can be exported for post-processing in other programs. RESULTS: The program can be used in multiple applications including the determination of cochlear dimensions, especially its length, and post-operative positions of cochlear implant (CI) electrode carriers. Computer-aided design models of the cochlea can be generated from exported marker points. CONCLUSION: The proposed DICOM viewer directly focuses on the needs of cochlear visualization, thus making it a valuable tool in CI related research. The ease of use facilitates future clinical use, e.g. for pre-operative selection of optimal CI electrode carrier length based on the patient's cochlear length. PMID- 26995597 TI - Hand-eye calibration for rigid laparoscopes using an invariant point. AB - PURPOSE: Laparoscopic liver resection has significant advantages over open surgery due to less patient trauma and faster recovery times, yet it can be difficult due to the restricted field of view and lack of haptic feedback. Image guidance provides a potential solution but one current challenge is in accurate "hand-eye" calibration, which determines the position and orientation of the laparoscope camera relative to the tracking markers. METHODS: In this paper, we propose a simple and clinically feasible calibration method based on a single invariant point. The method requires no additional hardware, can be constructed by theatre staff during surgical setup, requires minimal image processing and can be visualised in real time. Real-time visualisation allows the surgical team to assess the calibration accuracy before use in surgery. In addition, in the laboratory, we have developed a laparoscope with an electromagnetic tracking sensor attached to the camera end and an optical tracking marker attached to the distal end. This enables a comparison of tracking performance. RESULTS: We have evaluated our method in the laboratory and compared it to two widely used methods, "Tsai's method" and "direct" calibration. The new method is of comparable accuracy to existing methods, and we show RMS projected error due to calibration of 1.95 mm for optical tracking and 0.85 mm for EM tracking, versus 4.13 and 1.00 mm respectively, using existing methods. The new method has also been shown to be workable under sterile conditions in the operating room. CONCLUSION: We have proposed a new method of hand-eye calibration, based on a single invariant point. Initial experience has shown that the method provides visual feedback, satisfactory accuracy and can be performed during surgery. We also show that an EM sensor placed near the camera would provide significantly improved image overlay accuracy. PMID- 26995598 TI - Automatic data-driven real-time segmentation and recognition of surgical workflow. AB - PURPOSE: With the intention of extending the perception and action of surgical staff inside the operating room, the medical community has expressed a growing interest towards context-aware systems. Requiring an accurate identification of the surgical workflow, such systems make use of data from a diverse set of available sensors. In this paper, we propose a fully data-driven and real-time method for segmentation and recognition of surgical phases using a combination of video data and instrument usage signals, exploiting no prior knowledge. We also introduce new validation metrics for assessment of workflow detection. METHODS: The segmentation and recognition are based on a four-stage process. Firstly, during the learning time, a Surgical Process Model is automatically constructed from data annotations to guide the following process. Secondly, data samples are described using a combination of low-level visual cues and instrument information. Then, in the third stage, these descriptions are employed to train a set of AdaBoost classifiers capable of distinguishing one surgical phase from others. Finally, AdaBoost responses are used as input to a Hidden semi-Markov Model in order to obtain a final decision. RESULTS: On the MICCAI EndoVis challenge laparoscopic dataset we achieved a precision and a recall of 91 % in classification of 7 phases. CONCLUSION: Compared to the analysis based on one data type only, a combination of visual features and instrument signals allows better segmentation, reduction of the detection delay and discovery of the correct phase order. PMID- 26995599 TI - Soft tissue deformation for surgical simulation: a position-based dynamics approach. AB - PURPOSE: To assist the rehearsal and planning of robot-assisted partial nephrectomy, a real-time simulation platform is presented that allows surgeons to visualise and interact with rapidly constructed patient-specific biomechanical models of the anatomical regions of interest. Coupled to a framework for volumetric deformation, the platform furthermore simulates intracorporeal 2D ultrasound image acquisition, using preoperative imaging as the data source. This not only facilitates the planning of optimal transducer trajectories and viewpoints, but can also act as a validation context for manually operated freehand 3D acquisitions and reconstructions. METHODS: The simulation platform was implemented within the GPU-accelerated NVIDIA FleX position-based dynamics framework. In order to validate the model and determine material properties and other simulation parameter values, a porcine kidney with embedded fiducial beads was CT-scanned and segmented. Acquisitions for the rest position and three different levels of probe-induced deformation were collected. Optimal values of the cluster stiffness coefficients were determined for a range of different particle radii, where the objective function comprised the mean distance error between real and simulated fiducial positions over the sequence of deformations. RESULTS: The mean fiducial error at each deformation stage was found to be compatible with the level of ultrasound probe calibration error typically observed in clinical practice. Furthermore, the simulation exhibited unconditional stability on account of its use of clustered shape-matching constraints. CONCLUSIONS: A novel position-based dynamics implementation of soft tissue deformation has been shown to facilitate several desirable simulation characteristics: real-time performance, unconditional stability, rapid model construction enabling patient-specific behaviour and accuracy with respect to reference CT images. PMID- 26995600 TI - Edge map analysis in chest X-rays for automatic pulmonary abnormality screening. AB - PURPOSE: Our particular motivator is the need for screening HIV+ populations in resource-constrained regions for the evidence of tuberculosis, using posteroanterior chest radiographs (CXRs). METHOD: The proposed method is motivated by the observation that abnormal CXRs tend to exhibit corrupted and/or deformed thoracic edge maps. We study histograms of thoracic edges for all possible orientations of gradients in the range [Formula: see text] at different numbers of bins and different pyramid levels, using five different regions-of interest selection. RESULTS: We have used two CXR benchmark collections made available by the U.S. National Library of Medicine and have achieved a maximum abnormality detection accuracy (ACC) of 86.36 % and area under the ROC curve (AUC) of 0.93 at 1 s per image, on average. CONCLUSION: We have presented an automatic method for screening pulmonary abnormalities using thoracic edge map in CXR images. The proposed method outperforms previously reported state-of-the-art results. PMID- 26995601 TI - Random walks with shape prior for cochlea segmentation in ex vivo MUCT. AB - PURPOSE: Cochlear implantation is a safe and effective surgical procedure to restore hearing in deaf patients. However, the level of restoration achieved may vary due to differences in anatomy, implant type and surgical access. In order to reduce the variability of the surgical outcomes, we previously proposed the use of a high-resolution model built from [Formula: see text] images and then adapted to patient-specific clinical CT scans. As the accuracy of the model is dependent on the precision of the original segmentation, it is extremely important to have accurate [Formula: see text] segmentation algorithms. METHODS: We propose a new framework for cochlea segmentation in ex vivo [Formula: see text] images using random walks where a distance-based shape prior is combined with a region term estimated by a Gaussian mixture model. The prior is also weighted by a confidence map to adjust its influence according to the strength of the image contour. Random walks is performed iteratively, and the prior mask is aligned in every iteration. RESULTS: We tested the proposed approach in ten [Formula: see text] data sets and compared it with other random walks-based segmentation techniques such as guided random walks (Eslami et al. in Med Image Anal 17(2):236-253, 2013) and constrained random walks (Li et al. in Advances in image and video technology. Springer, Berlin, pp 215-226, 2012). Our approach demonstrated higher accuracy results due to the probability density model constituted by the region term and shape prior information weighed by a confidence map. CONCLUSION: The weighted combination of the distance-based shape prior with a region term into random walks provides accurate segmentations of the cochlea. The experiments suggest that the proposed approach is robust for cochlea segmentation. PMID- 26995602 TI - Retinal slit lamp video mosaicking. AB - PURPOSE: To this day, the slit lamp remains the first tool used by an ophthalmologist to examine patient eyes. Imaging of the retina poses, however, a variety of problems, namely a shallow depth of focus, reflections from the optical system, a small field of view and non-uniform illumination. For ophthalmologists, the use of slit lamp images for documentation and analysis purposes, however, remains extremely challenging due to large image artifacts. For this reason, we propose an automatic retinal slit lamp video mosaicking, which enlarges the field of view and reduces amount of noise and reflections, thus enhancing image quality. METHODS: Our method is composed of three parts: (i) viable content segmentation, (ii) global registration and (iii) image blending. Frame content is segmented using gradient boosting with custom pixel-wise features. Speeded-up robust features are used for finding pair-wise translations between frames with robust random sample consensus estimation and graph-based simultaneous localization and mapping for global bundle adjustment. Foreground aware blending based on feathering merges video frames into comprehensive mosaics. RESULTS: Foreground is segmented successfully with an area under the curve of the receiver operating characteristic curve of 0.9557. Mosaicking results and state-of-the-art methods were compared and rated by ophthalmologists showing a strong preference for a large field of view provided by our method. CONCLUSIONS: The proposed method for global registration of retinal slit lamp images of the retina into comprehensive mosaics improves over state-of-the-art methods and is preferred qualitatively. PMID- 26995603 TI - Preclinical usability study of multiple augmented reality concepts for K-wire placement. AB - PURPOSE: In many orthopedic surgeries, there is a demand for correctly placing medical instruments (e.g., K-wire or drill) to perform bone fracture repairs. The main challenge is the mental alignment of X-ray images acquired using a C-arm, the medical instruments, and the patient, which dramatically increases in complexity during pelvic surgeries. Current solutions include the continuous acquisition of many intra-operative X-ray images from various views, which will result in high radiation exposure, long surgical durations, and significant effort and frustration for the surgical staff. This work conducts a preclinical usability study to test and evaluate mixed reality visualization techniques using intra-operative X-ray, optical, and RGBD imaging to augment the surgeon's view to assist accurate placement of tools. METHOD: We design and perform a usability study to compare the performance of surgeons and their task load using three different mixed reality systems during K-wire placements. The three systems are interventional X-ray imaging, X-ray augmentation on 2D video, and 3D surface reconstruction augmented by digitally reconstructed radiographs and live tool visualization. RESULTS: The evaluation criteria include duration, number of X-ray images acquired, placement accuracy, and the surgical task load, which are observed during 21 clinically relevant interventions performed by surgeons on phantoms. Finally, we test for statistically significant improvements and show that the mixed reality visualization leads to a significantly improved efficiency. CONCLUSION: The 3D visualization of patient, tool, and DRR shows clear advantages over the conventional X-ray imaging and provides intuitive feedback to place the medical tools correctly and efficiently. PMID- 26995604 TI - Pure Cerebellar Ataxia with Homozygous Mutations in the PNPLA6 Gene. AB - Autosomal-recessive cerebellar ataxias (ARCA) are clinically and genetically heterogeneous conditions primarily affecting the cerebellum. Mutations in the PNPLA6 gene have been identified as the cause of hereditary spastic paraplegia and complex forms of ataxia associated with retinal and endocrine manifestations in a field where the genotype-phenotype correlations are rapidly expanding. We identified two cousins from a consanguineous family belonging to a large Zoroastrian (Parsi) family residing in Mumbai, India, who presented with pure cerebellar ataxia without chorioretinal dystrophy or hypogonadotropic hypogonadism. We used a combined approach of clinical characterisation, homozygosity mapping, whole-exome and Sanger sequencing to identify the genetic defect in this family. The phenotype in the family was pure cerebellar ataxia. Homozygosity mapping revealed one large region of shared homozygosity at chromosome 19p13 between affected individuals. Within this region, whole-exome sequencing of the index case identified two novel homozygous missense variants in the PNPLA6 gene at c.3847G>A (p.V1283M) and c.3929A>T (p.D1310V) in exon 32. Both segregated perfectly with the disease in this large family, with only the two affected cousins being homozygous. We identified for the first time PNPLA6 mutations associated with pure cerebellar ataxia in a large autosomal-recessive Parsi kindred. Previous mutations in this gene have been associated with a more complex phenotype but the results here suggest an extension of the associated disease spectrum. PMID- 26995605 TI - Utilization of pyrolytic substrate by microalga Chlamydomonas reinhardtii: cell membrane property change as a response of the substrate toxicity. AB - Acetic acid derived from fast pyrolysis of lignocellulosic biomass is a promising substrate for microalgae fermentation for producing lipid-rich biomass. However, crude pyrolytic acetic acid solution contains various toxic compounds inhibiting algal growth. It was hypothesized that such an inhibition was mainly due to the cell membrane damage. In this work, the cell membrane property of algal cells was evaluated at various conditions to elucidate the mechanisms of inhibition caused by the pyrolytic substrate solution. It was found that acetic acid itself served a carbon source for boosting algal cell growth but also caused cell membrane leakage. The acetic acid concentration for highest cell density was 4 g/L. Over liming treatment of crude pyrolytic acetic acid increased the algal growth with a concurrent reduction of cell membrane leakage. Directed evolution of algal strain enhanced cell membrane integrity and thus increased its tolerance to the toxicity of the crude substrate. Statistical analysis shows that there was a significant correlation between the cell growth performance and the cell membrane integrity (leakage) but not membrane fluidity. The addition of cyto-protectants such as Pluronic F68 and Pluronic F127 enhanced the cell membrane integrity and thus, resulted in enhanced cell growth. The transmission electron microscopy (TEM) of algal cells visually confirmed the cell membrane damage as the mechanism of the pyrolytic substrate inhibition. Collectively, this work indicates that the cell membrane is one major reason for the toxicity of pyrolytic acetic acid when being used for algal culture. To better use this pyrolytic substrate, cell membrane of the microorganism needs to be strengthened through either strain improvement or addition of membrane protectant reagents. PMID- 26995606 TI - Novel probes for pH and dissolved oxygen measurements in cultivations from millilitre to benchtop scale. AB - pH value and the concentration of dissolved oxygen (DO) are key parameters to monitor and control cell growth in cultivation studies. Reliable, robust and accurate methods to measure these parameters in cultivation systems in real time guarantee high product yield and quality. This mini-review summarises the current state of the art of pH and DO sensors that are applied to bioprocesses from millilitre to benchtop scale by means of a short introduction on measuring principles and selected applications. Special emphasis is placed on single-use bioreactors, which have been increasingly employed in bioprocess development and production in recent years. Working principles, applications and the particular requirements of sensors in these cultivation systems are given. In such processes, optical sensors for pH and DO are often preferred to electrochemical probes, as they allow semi-invasive measurements and can be miniaturised to micrometre scale or lower. In addition, selected measuring principles of novel sensing technologies for pH and DO are discussed. These include solid-state sensors and miniaturised devices that are not yet commercially available, but show promising characteristics for possible use in bioprocesses in the near future. PMID- 26995607 TI - Assessment of hydrogen metabolism in commercial anaerobic digesters. AB - Degradation of biomass in the absence of exogenous electron acceptors via anaerobic digestion involves a syntrophic association of a plethora of anaerobic microorganisms. The commercial application of this process is the large-scale production of biogas from renewable feedstock as an alternative to fossil fuels. After hydrolysis of polymers, monomers are fermented to short-chain fatty acids and alcohols, which are further oxidized to acetate. Carbon dioxide, molecular hydrogen (H2), and acetate generated during the process are converted to methane by methanogenic archaea. Since many of the metabolic pathways as well as the syntrophic interactions and dependencies during anaerobic digestion involve formation, utilization, or transfer of H2, its metabolism and the methanogenic population were assessed in various samples from three commercial biogas plants. Addition of H2 significantly increased the rate of methane formation, which suggested that hydrogenotrophic methanogenesis is not a rate-limiting step during biogas formation. Methanoculleus and Methanosarcina appeared to numerically dominate the archaeal population of the three digesters, but their proportion and the Bacteria-to-Archaea ratio did not correlate with the methane productivity. Instead, hydrogenase activity in cell-free extracts from digester sludge correlated with methane productivity in a positive fashion. Since most microorganisms involved in biogas formation contain this activity, it approximates the overall anaerobic metabolic activity and may, thus, be suitable for monitoring biogas reactor performance. PMID- 26995608 TI - Complete genome sequence of nucleoside producing strain Corynebacterium stationis ATCC 6872. AB - Corynebacterium stationis ATCC 6872 has been the subject of intense study in recent years with respect to various important industrial applications, such as nucleosides production. Here, the complete genome sequence for ATCC 6872 is presented. This bacterium harbors a 2,853,666bp circular genome that comprises 2487 coding CDS. PMID- 26995609 TI - Amides in Nature and Biocatalysis. AB - Amides are widespread in biologically active compounds with a broad range of applications in biotechnology, agriculture and medicine. Therefore, as alternative to chemical synthesis the biocatalytic amide synthesis is a very interesting field of research. As usual, Nature can serve as guide in the quest for novel biocatalysts. Several mechanisms for carboxylate activation involving mainly acyl-adenylate, acyl-phosphate or acyl-enzyme intermediates have been discovered, but also completely different pathways to amides are found. In addition to ribosomes, selected enzymes of almost all main enzyme classes are able to synthesize amides. In this review we give an overview about amide synthesis in Nature, as well as biotechnological applications of these enzymes. Moreover, several examples of biocatalytic amide synthesis are given. PMID- 26995610 TI - First draft genome sequencing of indole acetic acid producing and plant growth promoting fungus Preussia sp. BSL10. AB - Preussia sp. BSL10, family Sporormiaceae, was actively producing phytohormone (indole-3-acetic acid) and extra-cellular enzymes (phosphatases and glucosidases). The fungus was also promoting the growth of arid-land tree Boswellia sacra. Looking at such prospects of this fungus, we sequenced its draft genome for the first time. The Illumina based sequence analysis reveals an approximate genome size of 31.4Mbp for Preussia sp. BSL10. Based on ab initio gene prediction, total 32,312 coding sequences were annotated consisting of 11,967 coding genes, pseudogenes, and 221 tRNA genes. Furthermore, 321 carbohydrate-active enzymes were predicted and classified into many functional families. PMID- 26995611 TI - Immobilization of dehydrogenase onto epoxy-functionalized nanoparticles for synthesis of (R)-mandelic acid. AB - Epoxy functionalized magnetic Fe3O4@SiO2 nanoparticles were successfully prepared and characterized by Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The prepared nanoparticles were used for immobilization of alcohol dehydrogenase (ADH) from Saccharomyces cerevisiae by covalent attachment. The optimal immobilization conditions were obtained as follows: enzyme/support 4.49mg/g, pH 8.0, buffer concentration 0.05M, time 12h and temperature 30 degrees C. Under these conditions, a high immobilization yield and efficiency of above 92% were obtained after the optimization. Broad pH tolerance and high thermostability were achieved by the immobilization. The immobilized ADH retained about 84% initial activity after five cycles. Kinetic parameters Vmax and Km of free and immobilized ADH were determined as 56.72MUM/min, 44.27MUM/min and 11.54mM, 31.32mM, respectively. (R)-mandelic acid synthesis with the immobilized ADH was carried out, and the yield of (R)-mandelic acid was as high as 64%. These results indicate that the ADH immobilized onto epoxy-functionalized nanoparticles is an efficient and simple way for preparation of stable ADH, and the immobilized ADH has potential applications in the production of (R)-mandelic acid. PMID- 26995613 TI - Crystal structure and dynamics of Spt16N-domain of FACT complex from Cicer arietinum. AB - The facilitates chromatin transcription (FACT) complex, a heterodimer of SSRP1 and Spt16 proteins, is an essential histone chaperone that transiently reorganizes nucleosomes during transcription, replication and repair. N-terminal domain of Spt16 subunit (Spt16N) is strictly conserved in all the known Spt16 orthologs. Genetic studies in yeast have revealed a partially redundant role of Spt16N for the FACT functionality. Here, we report the crystal structure of Spt16N from a plant origin (Spt16Nca, Cicer arietinum) and its comparisons with the known Spt16N structures from yeasts and human. The inter-domain angle in Spt16Nca is significantly different from that of the yeast and human Spt16N structures. Normal mode analysis and classical molecular dynamics simulations reveal inter-domain movement in Spt16Nca and later also shows conformational flexibility of the critical loops. Spt16Nca binds to histone H3/H4 complex, similar to its orthologs from yeast and human origins. Further, conservation of electrostatic surface potentials in Spt16N structures from evolutionary distinct domains of eukaryotes (plant, human and fungi) have provided the potential sites on Spt16N for histone interactions. The structural comparisons with M24 peptidases show that the hydrophobic pocket shielded by a flexible loop of C terminal domain of Spt16N that may be functionally important. PMID- 26995612 TI - The potentiality of cross-linked fungal chitosan to control water contamination through bioactive filtration. AB - Water contamination, with heavy metals and microbial pathogens, is among the most dangerous challenges that confront human health worldwide. Chitosan is a bioactive biopolymer that could be produced from fungal mycelia to be utilized in various applied fields. An attempt to apply fungal chitosan for heavy metals chelation and microbial pathogens inhibition, in contaminated water, was performed in current study. Chitosan was produced from the mycelia of Aspergillus niger, Cunninghamella elegans, Mucor rouxii and from shrimp shells, using unified production conditions. The FT-IR spectra of produced chitosans were closely comparable. M. rouxii chitosan had the highest deacetylation degree (91.3%) and the lowest molecular weight (33.2kDa). All chitosan types had potent antibacterial activities against Escherichia coli and Staphylococcus aureus; the most forceful type was C. elegans chitosan. Chitosan beads were cross-linked with glutaraldehyde (GLA) and ethylene-glycol-diglycidyl ether (EGDE); linked beads became insoluble in water, acidic and alkaline solutions and could effectively adsorb heavy metals ions, e.g. copper, lead and zinc, in aqueous solution. The bioactive filter, loaded with EGDE- A. niger chitosan beads, was able to reduce heavy metals' concentration with >68%, and microbial load with >81%, after 6h of continuous water flow in the experimentally designed filter. PMID- 26995614 TI - Comprehensive study on the structure of the BSA from extended-to aged form in wide (2-12) pH range. AB - In this work we studied the structure of the bovine serum albumin (BSA) and the protein-ligand interactions since researchers prefer to use them as carriers in drug delivery systems. Systematic study (between pH 2-12, in double distilled water and physiological salt solution) was carried out to determine the changes in the secondary and the tertiary structures of the BSA, the apparent molecular weight (Mw), the size (dLS) and the electrokinetic potential (zeta). At pH 7, the BSA has higher stability in the absence (zeta=-69mV, dLS=2.2nm, A2=1.4*10( 3)mlmol/g(2)) than in the presence of salt solution (zeta=-2.4mV, dLS=5.3nm, A2= 3.2*10(-4)mlmol/g(2)). The Mw strongly depends on the pH and the ionic strength (at pH 3 in the absence of salt, the Mw is 54.6kDa while in the presence of salt is 114kDa) which determines the geometry of the protein. The protein-ligand interactions were characterized by fluorescence (FL) and isothermal microcalorimetry (ITC) methods; these independent techniques provided similar thermodynamic parameters such as the binding constant (K) and the Gibbs free energy (DeltaG). PMID- 26995615 TI - Comparative study of wastewater treatment and nutrient recycle via activated sludge, microalgae and combination systems. AB - Algal-bacterial synergistic cultivation could be an optional wastewater treatment technology in temperate areas. In this study, a locally screened vigorous Chlorella strain was characterized and then it was used in a comparative study of wastewater treatment and nutrient recycle assessment via activated sludge (AS), microalgae and their combination systems. Chlorella sp. cultured with AS in light showed the best performance, in which case the removal efficiencies of COD, NH3-N and TP were 87.3%, 99.2% and 83.9%, respectively, within a short period of 1day. Algal-bacterial combination in light had the best settleability. Chlorella sp. contained biomass, could be processed to feed, fertilizer or fuel due to the improved quality (higher C/H/N) compared with sludge. PCR-DGGE analysis shows that two types of rhizobacteria, namely, Pseudomonas putida and Flavobacterium hauense were enriched in sludge when cultured with algae in light, serving as the basics for artificial consortium construction for improved wastewater treatment. PMID- 26995616 TI - Isolation of a non-fermentative bacterium, Pseudomonas aeruginosa, using intracellular carbon for denitrification and phosphorus-accumulation and relevant metabolic mechanisms. AB - A newly designed pilot-scale system was developed to enrich denitrifying phosphate-accumulating organisms (DNPAOs) for nitrogen and phosphorus nutrient removal synchronously. A strain of DNPAOs was isolated and its biochemical characteristics and metabolic mechanisms of this bacterial strain were analyzed. The results showed that compared with previously reported system, this newly designed system has higher removal rates of nutrients. Removal efficiencies of NH3-N, TN, TP, and COD in actual wastewater were 82.64%, 79.62%, 87.22%, and 90.41%, respectively. Metabolic activity of DNPAOs after anoxic stage in this study even reached 94.64%. Pseudomonas aeruginosa is a strain of non-fermentative DNPAOs with strong nitrogen and phosphorus removal abilities. Study on the metabolic mechanisms suggested that intracellular PHB of P. aeruginosa plays dual roles, supplying energy for phosphorus accumulation and serving as a major carbon source for denitrification. PMID- 26995617 TI - A new method of two-phase anaerobic digestion for fruit and vegetable waste treatment. AB - A novel method of two-phase anaerobic digestion where the acid reactor is operated at low pH 4.0 was proposed and investigated. A completely stirred tank acid reactor and an up-flow anaerobic sludge bed methane reactor were operated to examine the possibility of efficient degradation of lactate and to identify their optimal operating conditions. Lactate with an average concentration of 14.8g/L was the dominant fermentative product and Lactobacillus was the predominant microorganism in the acid reactor. The effluent from the acid reactor was efficiently degraded in the methane reactor and the average methane yield was 261.4ml/gCOD removed. Organisms of Methanosaeta were the predominant methanogen in granular sludge of methane reactor, however, after acclimation hydrogenotrophic methanogens enriched, which benefited for the conversion of lactate to acetate. The two-phase AD system exhibited a low hydraulic retention time of 3.56days and high methane yield of 348.5ml/g VS removed. PMID- 26995618 TI - Energy efficient of ethanol recovery in pervaporation membrane bioreactor with mechanical vapor compression eliminating the cold traps. AB - An energy efficient pervaporation membrane bioreactor with mechanical vapor compression was developed for ethanol recovery during the process of fermentation coupled with pervaporation. Part of the permeate vapor at the membrane downstream under the vacuum condition was condensed by running water at the first condenser and the non-condensed vapor enriched with ethanol was compressed to the atmospheric pressure and pumped into the second condenser, where the vapor was easily condensed into a liquid by air. Three runs of fermentation-pervaporation experiment have been carried out lasting for 192h, 264h and 360h respectively. Complete vapor recovery validated the novel pervaporation membrane bioreactor. The total flux of the polydimethylsiloxane (PDMS) membrane was in the range of 350gm(-2)h(-1) and 600gm(-2)h(-1). Compared with the traditional cold traps condensation, mechanical vapor compression behaved a dominant energy saving feature. PMID- 26995619 TI - Long-term operation performance and variation of substrate tolerance ability in an anammox attached film expanded bed (AAFEB) reactor. AB - An anammox attached film expanded bed (AAFEB) reactor was operated to study the long-term performance and the variation of substrate tolerance ability. The results indicated that the nitrogen loading potential (NLP) was significantly enhanced from 13.56gN.(L.d)(-)(1) to 20.95gN.(L.d)(-)(1) during the stable operation period. The inhibitory concentration of 10% (IC10) for free ammonia (FA), free nitrous acid (FNA) and SNinf (diluted substrate concentration) increased from 18mg/L, 12MUgL(-1) and 370mgNL(-)(1) to 31mg/L, 19MUgL(-1) and 670mgNL(-)(1), respectively. However, the substrate shock of 2500mgNL(-)(1) for 24h terribly weakened the treatment performance and substrate tolerance ability of the reactor. The results of batch tests indicated that the existence of lag phase made the AAFEB reactor more vulnerable to substrate variation. The SNinf was accurate to be used to monitor the reactor performance and should be maintained below 320mgNL(-)(1) to ensure the absolute stable operation. PMID- 26995620 TI - Identifying patients who benefit from restrictive annuloplasty in ischemic mitral regurgitation: An elusive yet essential quest! Toward a patient-tailored approach. PMID- 26995621 TI - 2015 The American Association for Thoracic Surgery Consensus Guidelines: Ischemic mitral valve regurgitation. PMID- 26995622 TI - A new approach: Ischemic mitral regurgitation guidelines by and for surgeons. PMID- 26995623 TI - Surgery for aortic dilatation in patients with bicuspid aortic valves: A statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. AB - Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: The "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease" (J Am Coll Cardiol. 2010;55:e27-130) and the "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease" (J Am Coll Cardiol. 2014;63:e57-185). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline. PMID- 26995624 TI - A feasibility study of total endovascular aortic arch replacement: From stent graft design to preclinical testing. AB - OBJECTIVE: This study aimed to evaluate the safety and feasibility of total endovascular repair of the aortic arch using a novel designed stent-graft system (Yanger stent-graft system; Lifetech Scientific, Shenzhen, China) in vitro and in a canine model. METHODS: The Yanger stent-graft system is composed of a main stent-graft, branched stent-graft, and a delivery system. In an in vitro aortic arch simulation test bench, the system was tested, and the success rate of stent graft releasing, anchoring, and positioning was recorded and analyzed. Meanwhile, in vivo implantation of the Yanger stent-graft system was carried out in 16 healthy adult crossbreed dogs. The feasibility of using these stent-grafts was evaluated with aortography, multislice computed tomography, and autopsy 6 months after the procedure. RESULTS: All stent-graft releasing and positioning were successful for in vitro test. In the canine model, the Yanger stent-graft system was placed successfully in the aortic arch in all 14 dogs with the exception of 2 mortalities. All dogs survived for at least 3 months with normal physiologic signs. Aortography, multislice computed tomography, and animal necropsy revealed good fixation in all cases. The ascending aorta, descending aorta, brachiocephalic trunk, and left subclavian artery were all covered without endoleak. There was no significant obstruction or stenosis in brachiocephalic branches at the 6-month follow-up. CONCLUSIONS: Total endovascular repair of aortic arch with the novel designed Yanger stent-graft system is safe and feasible in preclinical studies. With a better understanding of preclinical knowledge, patient selection criteria and first-in-human studies will be addressed. PMID- 26995625 TI - A victory for all Halstedians: Evidence supporting cardiac surgical residents training. PMID- 26995626 TI - The evidence is suspect. PMID- 26995627 TI - Frozen elephant trunk versus single-stage open repair for extensive thoracic aortic disease. PMID- 26995628 TI - Extracorporeal cardiopulmonary resuscitation for out-of-hospital refractory cardiac arrest: A word of caution. PMID- 26995629 TI - Surgeon volume and procedure selection. PMID- 26995630 TI - The effect of surgeon volume on procedure selection in non-small cell lung cancer surgeries. PMID- 26995631 TI - More than one way to skin a cat. PMID- 26995632 TI - Personalized therapy for hepatocellular carcinoma: Where are we now? AB - Following the approval of sorafenib, a large number of molecular targeted agents have been tested clinically for advanced hepatocellular carcinoma (HCC), but all have failed to demonstrate significant efficacy in clinical trials. Multiple reasons for this phenomenon have been discussed in the literature, with one reason being the lack of patient selection on the basis of molecular profile in clinical trials. The concept of drug testing in selected populations has been recently suggested by retrospective analyses of HCC clinical trials in which a particular subgroup of patients, either enriched by clinical factors or by tissue biomarkers, derived more benefits from the novel drug. In addition, recent advances in genomic medicine have enhanced the understanding of genetic and epigenetic events occurring in HCC, raising the possibility of personalizing targeted agents in accordance with the genetic make-up of the tumors. The development of 'personalized' treatment for HCC is, however, hindered by the lack of fresh biopsy of advanced HCC, the low incidence of genetic driver mutations in HCC and the tumor heterogeneity. These limitations may be overcome by sequencing cell-free DNA in plasma, frequently known as liquid biopsy, and revolution in the concept of the design of clinical trials. In this review article, we aim to: (1) give a summary of the recent sequencing results of HCC and the related implications for drug development; (2) highlight potential individual targeted agents and existing research on biomarker selection in clinical trials; and (3) discuss future directions, including the potential of liquid biopsy and umbrella clinical trials, to enhance personalized drug testing for HCC. PMID- 26995633 TI - New insights on PI3K/AKT pathway alterations and clinical outcomes in breast cancer. AB - PI3K/AKT signaling pathway plays an important role in tumorigenesis and regulates critical cellular functions including survival, proliferation and metabolism. PIK3CA mutations and AKT activation by phosphorylation (pAKT) are often detected in many cancers and especially at high frequencies in breast cancer. Mounting data suggest that PIK3CA mutations or pAKT are mostly associated with better or insignificant outcomes in estrogen receptor-positive (ER+) early stage breast cancer and tend to be with worse prognosis in ER- disease. pAKT expression has been identified to predict paclitaxel chemotherapy benefit in node-positive breast cancer. Preclinical and neoadjuvant trial data suggest that PIK3CA alterations confer resistance to HER2-targeted therapy and are associated with lower pathological complete response (pCR) rate in HER2-positive breast cancer. However, recent results from randomized clinical trials of adjuvant and metastatic settings show that patients with mutant and wildtype PIK3CA tumors derived similar benefit from anti-HER2 therapy. This article, with our new insights, aims to decipher the mixed data and discusses the influence of the potential confounding factors in the assessments. We also share our views for validation of PI3K/AKT alterations in relation to clinical outcome in the context of specific breast cancer subtypes and treatment modalities towards further advance of the precision medicine for breast cancer treatment. PMID- 26995635 TI - Reflections on the diagnostic accuracy of the Upper Limb Neurodynamic Test 1. PMID- 26995634 TI - Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high-frequency heart rate variability. AB - Resting high-frequency heart rate variability (HF-HRV) relates to cardiac vagal control and predicts individual differences in health and longevity, but its functional neural correlates are not well defined. The medial prefrontal cortex (mPFC) encompasses visceral control regions that are components of intrinsic networks of the brain, particularly the default mode network (DMN) and the salience network (SN). Might individual differences in resting HF-HRV covary with resting state neural activity in the DMN and SN, particularly within the mPFC? This question was addressed using fMRI data from an eyes-open, 5-min rest period during which echoplanar brain imaging yielded BOLD time series. Independent component analysis yielded functional connectivity estimates defining the DMN and SN. HF-HRV was measured in a rest period outside of the scanner. Midlife (52% female) adults were assessed in two studies (Study 1, N = 107; Study 2, N = 112). Neither overall DMN nor SN connectivity strength was related to HF-HRV. However, HF-HRV related to connectivity of one region within mPFC shared by the DMN and SN, namely, the perigenual anterior cingulate cortex, an area with connectivity to other regions involved in autonomic control. In sum, HF-HRV does not seem directly related to global resting state activity of intrinsic brain networks, but rather to more localized connectivity. A mPFC region was of particular interest as connectivity related to HF-HRV was shared by the DMN and SN. These findings may indicate a functional basis for the coordination of autonomic cardiac control with engagement and disengagement from the environment. PMID- 26995636 TI - Positive lists of cosmetic ingredients: Analytical methodology for regulatory and safety controls - A review. AB - Cosmetic products placed on the market and their ingredients, must be safe under reasonable conditions of use, in accordance to the current legislation. Therefore, regulated and allowed chemical substances must meet the regulatory criteria to be used as ingredients in cosmetics and personal care products, and adequate analytical methodology is needed to evaluate the degree of compliance. This article reviews the most recent methods (2005-2015) used for the extraction and the analytical determination of the ingredients included in the positive lists of the European Regulation of Cosmetic Products (EC 1223/2009): comprising colorants, preservatives and UV filters. It summarizes the analytical properties of the most relevant analytical methods along with the possibilities of fulfilment of the current regulatory issues. The cosmetic legislation is frequently being updated; consequently, the analytical methodology must be constantly revised and improved to meet safety requirements. The article highlights the most important advances in analytical methodology for cosmetics control, both in relation to the sample pretreatment and extraction and the different instrumental approaches developed to solve this challenge. Cosmetics are complex samples, and most of them require a sample pretreatment before analysis. In the last times, the research conducted covering this aspect, tended to the use of green extraction and microextraction techniques. Analytical methods were generally based on liquid chromatography with UV detection, and gas and liquid chromatographic techniques hyphenated with single or tandem mass spectrometry; but some interesting proposals based on electrophoresis have also been reported, together with some electroanalytical approaches. Regarding the number of ingredients considered for analytical control, single analyte methods have been proposed, although the most useful ones in the real life cosmetic analysis are the multianalyte approaches. PMID- 26995637 TI - Development of an analytical method for the determination of polybrominated diphenyl ethers in sewage sludge by the use of gas chromatography coupled to inductively coupled plasma mass spectrometry. AB - Polybrominated diphenyl ethers (PBDEs) are flame retardants. As a consequence of their widespread use, they have been released into the environment. PBDEs are lipophilic organic contaminants that enter wastewater treatment plants (WWTPs) from urban, agricultural and industrial discharges. Because of their low aqueous solubility and resistance to biodegradation, up to 90% of the PBDEs are accumulated in the sewage sludge during the wastewater treatment. To assess the possibilities for sludge re-use, a reliable determination of the concentrations of these PBDEs is of crucial importance. Six PBDE congeners (BDE 28, BDE 47, BDE 99, BDE 100, BDE 153 and BDE 154) are listed as priority substances under the EU Water Framework Directive. In the present work a simple analytical method with minimal sample-preparation steps was developed for a sensitive and reliable determination of the six PBDEs in sewage sludge by the use of gas chromatography coupled to inductively coupled plasma mass spectrometry (GC-ICP-MS). For this purpose an extraction procedure was optimised. Different extracting agents (methanol (MeOH), acetic acid (AcOH)/MeOH mixture (3:1) and 0.1 mol L(-1) hydrochloric acid (HCl) in MeOH) followed by the addition of a Tris-citrate buffer (co-extracting agent) and iso-octane were applied under different modes of extraction (mechanical shaking, microwave- and ultrasound-assisted extraction). Mechanical shaking or the microwave-assisted extraction of sewage sludge with 0.1 mol L(-1) HCl in MeOH and the subsequent addition of the Tris-citrate buffer and the iso-octane extracted the PBDEs from the complex sludge matrix most effectively. However, due to easier sample manipulation during the extraction step, mechanical shaking was used. The PBDEs in the organic phase were quantified with GC-ICP-MS by applying a standard addition calibration method. The spike recovery test (recoveries between 95 and 104%) and comparative analyses with the species-specific isotope-dilution (ID) GC-ICP-MS confirmed the accuracy of the developed analytical procedure. The procedure is sensitive (limits of detection (LODs) for PBDEs congeners between 0.2 and 0.3 ng g(-1)), repeatable and reproducible (RSDs 2.2-5.7%) and was applied for the determination of PBDEs in sewage sludge samples collected three times at the municipal WWTP over a period of 16 years. PMID- 26995638 TI - Characterization of surfactant complex mixtures using Raman spectroscopy and signal extraction methods: Application to laundry detergent deformulation. AB - This paper presents the analysis of surfactants in complex mixtures using Raman spectroscopy combined with signal extraction (SE) methods. Surfactants are the most important component in laundry detergents. Both their identification and quantification are required for quality control and regulation purposes. Several synthetic mixtures of four surfactants contained in an Ecolabel laundry detergent were prepared and analyzed by Raman spectroscopy. SE methods, Independent Component Analysis and Multivariate Curve Resolution, were then applied to spectral data for surfactant identification and quantification. The influence of several pre-processing treatments (normalization, baseline correction, scatter correction and smoothing) on SE performances were evaluated by experimental design. By using optimal pre-processing strategy, SE methods allowed satisfactorily both identifying and quantifying the four surfactants. When applied to the pre-processed Raman spectrum of the Ecolabel laundry detergent sample, SE models remained robust enough to predict the surfactant concentrations with sufficient precision for deformulation purpose. Comparatively, a supervised modeling technique (PLS regression) was very efficient to quantify the four surfactants in synthetic mixtures but appeared less effective than SE methods when applied to the Raman spectrum of the detergent sample. PLS seemed too sensitive to the other components contained in the laundry detergent while SE methods were more robust. The results obtained demonstrated the interest of SE methods in the context of deformulation. PMID- 26995639 TI - Mercury determination in urine samples by gold nanostructured screen-printed carbon electrodes after vortex-assisted ionic liquid dispersive liquid-liquid microextraction. AB - A novel approach is presented to determine mercury in urine samples, employing vortex-assisted ionic liquid dispersive liquid-liquid microextraction and microvolume back-extraction to prepare samples, and screen-printed electrodes modified with gold nanoparticles for voltammetric analysis. Mercury was extracted directly from non-digested urine samples in a water-immiscible ionic liquid, being back-extracted into an acidic aqueous solution. Subsequently, it was determined using gold nanoparticle-modified screen-printed electrodes. Under optimized microextraction conditions, standard addition calibration was applied to urine samples containing 5, 10 and 15 MUg L(-1) of mercury. Standard addition calibration curves using standards between 0 and 20 MUg L(-1) gave a high level of linearity with correlation coefficients ranging from 0.990 to 0.999 (N = 5). The limit of detection was empirical and statistically evaluated, obtaining values that ranged from 0.5 to 1.5 MUg L(-1), and from 1.1 to 1.3 MUg L(-1), respectively, which are significantly lower than the threshold level established by the World Health Organization for normal mercury content in urine (i.e., 10-20 MUg L(-1)). A certified reference material (REC-8848/Level II) was analyzed to assess method accuracy finding 87% and 3 MUg L(-1) as the recovery (trueness) and standard deviation values, respectively. Finally, the method was used to analyze spiked urine samples, obtaining good agreement between spiked and found concentrations (recovery ranged from 97 to 100%). PMID- 26995640 TI - Matrix removal in state of the art sample preparation methods for serum by charged aerosol detection and metabolomics-based LC-MS. AB - Investigations into sample preparation procedures usually focus on analyte recovery with no information provided about the fate of other components of the sample (matrix). For many analyses, however, and particularly those using liquid chromatography-mass spectrometry (LC-MS), quantitative measurements are greatly influenced by sample matrix. Using the example of the drug amitriptyline and three of its metabolites in serum, we performed a comprehensive investigation of nine commonly used sample clean-up procedures in terms of their suitability for preparing serum samples. We were monitoring the undesired matrix compounds using a combination of charged aerosol detection (CAD), LC-CAD, and a metabolomics based LC-MS/MS approach. In this way, we compared analyte recovery of protein precipitation-, liquid-liquid-, solid-phase- and hybrid solid-phase extraction methods. Although all methods provided acceptable recoveries, the highest recovery was obtained by protein precipitation with acetonitrile/formic acid (amitriptyline 113%, nortriptyline 92%, 10-hydroxyamitriptyline 89%, and amitriptyline N-oxide 96%). The quantification of matrix removal by LC-CAD showed that the solid phase extraction method (SPE) provided the lowest remaining matrix load (48-123 MUg mL(-1)), which is a 10-40 fold better matrix clean-up than the precipitation- or hybrid solid phase extraction methods. The metabolomics profiles of eleven compound classes, comprising 70 matrix compounds showed the trends of compound class removal for each sample preparation strategy. The collective data set of analyte recovery, matrix removal and matrix compound profile was used to assess the effectiveness of each sample preparation method. The best performance in matrix clean-up and practical handling of small sample volumes was showed by the SPE techniques, particularly HLB SPE. CAD proved to be an effective tool for revealing the considerable differences between the sample preparation methods. This detector can be used to follow matrix compound elution during chromatographic separations, and the facile monitoring of matrix signal can assist in avoiding unfavourable matrix effects on analyte quantification. PMID- 26995641 TI - Characterizing nonconstant instrumental variance in emerging miniaturized analytical techniques. AB - Measurement variance is a crucial aspect of quantitative chemical analysis. Variance directly affects important analytical figures of merit, including detection limit, quantitation limit, and confidence intervals. Most reported analyses for emerging analytical techniques implicitly assume constant variance (homoskedasticity) by using unweighted regression calibrations. Despite the assumption of constant variance, it is known that most instruments exhibit heteroskedasticity, where variance changes with signal intensity. Ignoring nonconstant variance results in suboptimal calibrations, invalid uncertainty estimates, and incorrect detection limits. Three techniques where homoskedasticity is often assumed were covered in this work to evaluate if heteroskedasticity had a significant quantitative impact-naked-eye, distance based detection using paper-based analytical devices (PADs), cathodic stripping voltammetry (CSV) with disposable carbon-ink electrode devices, and microchip electrophoresis (MCE) with conductivity detection. Despite these techniques representing a wide range of chemistries and precision, heteroskedastic behavior was confirmed for each. The general variance forms were analyzed, and recommendations for accounting for nonconstant variance discussed. Monte Carlo simulations of instrument responses were performed to quantify the benefits of weighted regression, and the sensitivity to uncertainty in the variance function was tested. Results show that heteroskedasticity should be considered during development of new techniques; even moderate uncertainty (30%) in the variance function still results in weighted regression outperforming unweighted regressions. We recommend utilizing the power model of variance because it is easy to apply, requires little additional experimentation, and produces higher precision results and more reliable uncertainty estimates than assuming homoskedasticity. PMID- 26995643 TI - Au nanoparticles grafted on Fe3O4 as effective SERS substrates for label-free detection of the 16 EPA priority polycyclic aromatic hydrocarbons. AB - Several methods and materials have been explored for the sensitive and practicable detection of polycyclic aromatic hydrocarbons (PAHs). However, it is still a challenge to develop simple and cost-effective sensing techniques for PAHs. Herein we report the synthesis and construction of Fe3O4@Au SERS substrate. This magnetic substrate was composed by Fe3O4 microspheres and Au NPs. The size, morphology, and surface composition of Fe3O4@Au were characterized by multiple complimentary techniques including scanning electron microscopy, X-ray photoelectron spectroscopy, and X-ray powder diffraction. The spatial distributions of electro-magnetic field enhancement around Fe3O4@Au was calculated using finite difference time domain (FDTD) simulations. As a result of its remarkable sensitivity, the Fe3O4@Au-based SERS assay has been applied to detect the 16 EPA priority PAHs. The LODs achieved by our method (100-5 nM, 16.6 1.01 MUg L(-1)) make it promising for the rapid screening of highly contaminated cases. As a proof-of-concept study, the substrate was applied in SERS sensing of PAHs in river matrix. The 16 PAHs could be differentiated based upon their characteristic SERS peaks. Most importantly, the detection was successfully conducted using a portable Raman spectrometer, which could be used for on-site monitoring of PAHs. PMID- 26995642 TI - Colorimetric detection of urea, urease, and urease inhibitor based on the peroxidase-like activity of gold nanoparticles. AB - Herein, we reported for the first time that gold nanoparticles-catalyzed 3,3',5,5'-tetramethylbenzidine-H2O2 system can serve as an ultrasensitive colorimetric pH indicator. Gold nanoparticles acted as a catalyst and imitated the function of horseradish peroxidase. The absorbance at 450 nm of the yellow color product in the catalytic reaction exhibited a linear fashion over the pH range of 6.40-6.60. On the basis of this property, we constructed a novel sensing platform for the determination of urea, urease, and urease inhibitor. The limit of detection for urea and urease was 5 MUM and 1.8 U/L, respectively. The half maximal inhibition value IC50 of acetohydroxamic acid was found to be 0.05 mM. Urea in human urine and urease in soil were detected with satisfied results. PMID- 26995644 TI - Limits of rapid log P determination methods for highly lipophilic and flexible compounds. AB - Lipophilicity is of crucial importance in many fields including pharmaceutical, environmental, cosmetic and food industries. Whereas different experimental strategies have been developed for rapid lipophilicity determination of new chemical entities, log P determination of highly lipophilic compounds is always challenging. In this study, three published chromatographic methods have been compared on a series of phenylalkanoic acids including the pro-perfume HaloscentD (HD-C12). Different log P values were obtained depending on the chromatographic method used for log P estimation. Molecular modelling suggested that log P variations may be due to the chromatographic conditions applied (isocratic or gradient mode, ratio methanol/water in the mobile phase), responsible of specific conformations of the molecule in solution. Thus, for flexible compounds, published methods have to be used with caution and considered as a good tool to estimate a log P range, depending on the molecular conformational state. PMID- 26995645 TI - Fast and sensitive supercritical fluid chromatography - tandem mass spectrometry multi-class screening method for the determination of doping agents in urine. AB - This study shows the possibility offered by modern ultra-high performance supercritical fluid chromatography combined with tandem mass spectrometry in doping control analysis. A high throughput screening method was developed for 100 substances belonging to the challenging classes of anabolic agents, hormones and metabolic modulators, synthetic cannabinoids and glucocorticoids, which should be detected at low concentrations in urine. To selectively extract these doping agents from urine, a supported liquid extraction procedure was implemented in a 48-well plate format. At the tested concentration levels ranging from 0.5 to 5 ng/mL, the recoveries were better than 70% for 48-68% of the compounds and higher than 50% for 83-87% of the tested substances. Due to the numerous interferences related to isomers of steroids and ions produced by the loss of water in the electrospray source, the choice of SFC separation conditions was very challenging. After careful optimization, a Diol stationary phase was employed. The total analysis time for the screening assay was only 8 min, and interferences as well as susceptibility to matrix effect (ME) were minimized. With the developed method, about 70% of the compounds had relative ME within the range +/ 20%, at a concentration of 1 and 5 ng/mL. Finally, limits of detection achieved with the above-described strategy including 5-fold preconcentration were below 0.1 ng/mL for the majority of the tested compounds. Therefore, LODs were systematically better than the minimum required performance levels established by the World anti-doping agency, except for very few metabolites. PMID- 26995646 TI - A novel aldo-keto reductase from Jatropha curcas L. (JcAKR) plays a crucial role in the detoxification of methylglyoxal, a potent electrophile. AB - Abiotic stress leads to the generation of reactive oxygen species (ROS) which further results in the production of reactive carbonyls (RCs) including methylglyoxal (MG). MG, an alpha, beta-dicarbonyl aldehyde, is highly toxic to plants and the mechanism behind its detoxification is not well understood. Aldo keto reductases (AKRs) play a role in detoxification of reactive aldehydes and ketones. In the present study, we cloned and characterised a putative AKR from Jatropha curcas (JcAKR). Phylogenetically, it forms a small clade with AKRs of Glycine max and Rauwolfia serpentina. JcAKR was heterologously expressed in Escherichia coli BL-21(DE3) cells and the identity of the purified protein was confirmed through MALDI-TOF analysis. The recombinant protein had high enzyme activity and catalytic efficiency in assays containing MG as the substrate. Protein modelling and docking studies revealed MG was efficiently bound to JcAKR. Under progressive drought and salinity stress, the enzyme and transcript levels of JcAKR were higher in leaves compared to roots. Further, the bacterial and yeast cells expressing JcAKR showed more tolerance towards PEG (5%), NaCl (200mM) and MG (5mM) treatments compared to controls. In conclusion, our results project JcAKR as a possible and potential target in crop improvement for abiotic stress tolerance. PMID- 26995647 TI - A developmental perspective on the neural bases of human empathy. AB - While empathy has been widely studied in philosophical and psychological literatures, recent advances in social neuroscience have shed light on the neural correlates of this complex interpersonal phenomenon. In this review, we provide an overview of brain imaging studies that have investigated the neural substrates of human empathy. Based on existing models of the functional architecture of empathy, we review evidence of the neural underpinnings of each main component, as well as their development from infancy. Although early precursors of affective sharing and self-other distinction appear to be present from birth, recent findings also suggest that even higher-order components of empathy such as perspective-taking and emotion regulation demonstrate signs of development during infancy. This merging of developmental and social neuroscience literature thus supports the view that ontogenic development of empathy is rooted in early infancy, well before the emergence of verbal abilities. With age, the refinement of top-down mechanisms may foster more appropriate empathic responses, thus promoting greater altruistic motivation and prosocial behaviors. PMID- 26995648 TI - Characterization and automatic screening of reactive and abnormal neoplastic B lymphoid cells from peripheral blood. AB - INTRODUCTION: The objective was to advance in the automatic, image-based, characterization and recognition of a heterogeneous set of lymphoid cells from peripheral blood, including normal, reactive, and five groups of abnormal lymphocytes: hairy cells, mantle cells, follicular lymphoma, chronic lymphocytic leukemia, and prolymphocytes. METHODS: A number of 4389 images from 105 patients were selected by pathologists, based on morphologic visual appearance, from patients whose diagnosis was confirmed by all the remaining complementary tests. Besides geometry, new color and texture features were extracted using six alternative color spaces to obtain rich information to characterize the cell groups. The recognition system was designed using support vector machines trained with the whole image set. RESULTS: In the experimental tests, individual sets of images from 21 new patients were analyzed by the trained recognition system and compared with the true diagnosis. An overall recognition accuracy of 97.67% was achieved when the cell screening was performed into three groups: normal lymphocytes, abnormal lymphoid cells, and reactive lymphocytes. The accuracy of the whole experimental study was 91.23% when considering the further discrimination of the abnormal lymphoid cells into the specific five groups. CONCLUSION: The excellent automatic screening of the three groups of normal, reactive, and abnormal lymphocytes is useful as it discriminates between malignancy and not malignancy. The discrimination of the five groups of abnormal lymphoid cells is encouraging toward the idea that the system could be an automated image-based screening method to identify blood involvement by a variety of B lymphomas. PMID- 26995649 TI - The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants. AB - AIMS/HYPOTHESIS: The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. METHODS: HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. RESULTS: Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants. CONCLUSIONS/INTERPRETATION: Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue. PMID- 26995650 TI - PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes. AB - AIMS/HYPOTHESIS: The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP) mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury. METHODS: Male Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption. RESULTS: Ep 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. CONCLUSIONS/INTERPRETATION: Taken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease. PMID- 26995651 TI - The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy. AB - Adverse neonatal outcomes continue to be high for mothers with type 1 and type 2 diabetes, and are far from eliminated in mothers with gestational diabetes mellitus. This is often despite seemingly satisfactory glycaemic control in the latter half of pregnancy. Here we argue that this could be a consequence of the early establishment of fetal hyperinsulinaemia, a driver that exaggerates the fetal glucose steal. Essentially, fetal hyperinsulinaemia, through its effect on lowering fetal glycaemia, will increase the glucose concentration gradient across the placenta and consequently the glucose flux to the fetus. While the steepness of this gradient and glucose flux will be greatest at times when maternal hyperglycaemia and fetal hyperinsulinaemia coexist, fetal hyperinsulinaemia will favour a persistently high glucose flux even at times when maternal blood glucose is normal. The obvious implication is that glycaemic control needs to be optimised very early in pregnancy to prevent the establishment of fetal hyperinsulinaemia, further supporting the need for pre-pregnancy planning and early establishment of maternal glycaemic control. An exaggerated glucose steal by a hyperinsulinaemic fetus could also attenuate maternal glucose levels during an OGTT, providing an explanation for why some mothers with fetuses with all the characteristics of diabetic fetopathy have 'normal' glucose tolerance. PMID- 26995652 TI - KLF8 knockdown triggered growth inhibition and induced cell phase arrest in human pancreatic cancer cells. AB - BACKGROUND: The transcription factor Kruppel-like factor 8 (KLF8) plays an important role in tumor development and growth, but its role in pancreatic cancer (PC) is not clear. METHODS: KLF8 expression in human PC cell lines and tumor tissues was measured by quantitative real-time polymerase chain reaction and Western blot analyses. The effects of lentivirus mediated knockdown of KLF8 on proliferation and growth in Panc-1 pancreatic cancer cells were examined. RESULTS: KLF8 was overexpressed in 5 pancreatic cancer cell lines and in samples from patients with PC. In Panc-1 cells, KLF8 knockdown inhibited cell proliferation, tumorigenicity, and induced G2/M phase arrest. KLF8 knockdown suppressed PC tumor growth in nude mice model. Western blot analysis showed that KLF8 knockdown in Panc-1 cells down-regulated the expression of CDK1/CDC2, cyclin B1, and cyclin D1 and up-regulated the expression of p21, and p27. CONCLUSIONS: Overexpression of KLF8 may contribute to the progression of pancreatic cancer, and downregulation of KLF8 expression by lentivirus-delivered shRNA is a novel therapeutic approach for PC. PMID- 26995653 TI - Impacts of common variants in ALDH2 on coronary artery disease patients. AB - Genome-wide association studies (GWAS) have identified Aldehyde dehydrogenase 2 (ALDH2) as a susceptibility locus for coronary artery disease (CAD) previously. However, the impacts of common variants in this gene on CAD and its outcomes have not been extensively studied. This study explored the association between the Tagging SNPs in ALDH2 and CAD as well as its main outcomes. Six common variants in ALDH2 were selected as tagging SNPs and two cohorts containing 7296 individuals were genotyped to investigate the impacts of ALDH2 on CAD and its main outcomes. The results show that the variant rs671 in ALDH2 is associated with an increased risk of CAD in southern Chinese (OR=1.26, 95%CI: 1.07-1.48, p=0.004), while not in northern Chinese (OR=1.00, 95%CI: 0.86-1.50, p=0.94). Meanwhile, we find that rs671 genotypes may not influence the outcomes of CAD (HR=1.11, 95%CI: 0.892-1.38, p=0.346). Additionally, we also tested the effect of rs671 genotype on CAD severity, while no significant association was found between them. In the subgroup analysis, the results revealed that rs671 were significantly associated with CAD (OR=1.24, 95%CI: 1.11-1.38, p<0.001) in non alcoholic subjects. Overall, our findings indicate that the associations between rs671 in ALDH2 and CAD are regional disparity, and rs671 genotypes may not influence the main outcomes of CAD. PMID- 26995655 TI - The Out of Africa hypothesis and the ancestry of recent humans: Cherchez la femme (et l'homme). AB - The Out of Africa hypothesis (OOAH) has been a mainstay in the discussion of human evolution since its presentation in the 1980's. However, recent advances in palaeontology and molecular genetics have made it possible to examine the hypothesis in a manner that was inconceivable at the time of its proposal. The palaeontological progress relates to early Homo finds in the Caucasus, Denisova finds in the Altai Mountains and Neanderthal finds in a wide range of localities from the Altai Mountains, the Caucasus, the Levant, Asia Minor, southern and Central Europe and the Iberian Peninsula. The Eurasian location of these finds and recognition of the principle of Last common ancestor (LCA) lend no support to OOAH. The same conclusion is drawn from genomic findings, which (a) have revealed the presence of Denisovan and Neanderthal nuclear DNA, primarily in the genomes of recent Eurasians and (b) have shown genomic introgression from early modern humans into Neanderthals in the Altai Mountains. Similarly, archaeological finds in Sulawesi and the discovery of ~100,000years old human teeth in southern China constitute strong independent challenges to OOAH. The genomic and palaeogenomic results and the new palaeontological and archaeological discoveries suggest (a) that the ancestors of modern humans had their origin in a Eurasian (largely Asian) biogeographic region which may also have extended into NE Africa, and (b) that the founders of basal African lineages became separated, geographically and genetically, in the westernmost part of this region and spread from there to different parts of the African continent. PMID- 26995654 TI - Transcriptome analysis of phycocyanin inhibitory effects on SKOV-3 cell proliferation. AB - Phycocyanin (PC) from Spirulina platensis has inhibitory effects on tumor cell growth. In this research, the transcriptome study was designed to investigate the underlying molecular mechanisms of PC inhibition on human ovarian cancer cell SKOV-3 proliferation. The PC IC50 was 216.6MUM and 163.8MUM for 24h and 48h exposure, respectively, as determined by CCK-8 assay. The morphological changes of SKOV-3 cells after PC exposure were recorded using HE staining. Cells arrested in G2/M stages as determined by flow cytometry. The transcriptome analysis showed that 2031 genes (with > three-fold differences) were differentially expressed between the untreated and the PC-treated cells, including 1065 up-regulated and 966 down-regulated genes. Gene ontology and KEGG pathway analysis identified 18 classical pathways that were remarkably enriched, such as neurotrophin signaling pathway, VEGF signaling pathway and P53 signaling pathway. qPCR results further showed that PTPN12, S100A2, RPL26, and LAMA3 increased while HNRNPA1P10 decreased in PC-treated cells. Molecules and genes in those pathways may be potential targets to develop treatments for ovarian cancer. PMID- 26995656 TI - The Generation of an Organic Inverted Chemical Garden. AB - A chemical garden based on iron salt that grows in organic solvents and ions is demonstrated for the first time. This prototype chemical garden develops in an inverted orientation, thus providing evidence that downward growth is feasible. PMID- 26995657 TI - Semen residual viral load and reproductive outcomes in HIV-infected men undergoing ICSI after extended semen preparation. AB - The aim of this study was to evaluate the residual presence of the human immunodeficiency virus (HIV) following a triple gradient extended semen wash from ejaculates of serodiscordant couples, and analyse their reproductive outcomes after intracytoplasmic sperm injection (ICSI). For this purpose, a retrospective analysis of our database was performed in serodiscordant couples, with HIV infected men and non-infected women, using fresh or frozen sperm with ICSI in oocytes from either the patients or donors from January 2006 to September 2013. Overall, the rate of positive HIV test after semen washing was 1.86%. The positive beta human chorionic gonadotrophin, clinical and ongoing pregnancy rates in patients with their own oocytes were 47.1%, 37.5% and 30.8%, respectively, and 58.6%, 50.8% and 39.1%, respectively, in oocyte donation cycles. To summarize, the described method of sperm washing based on triple gradient sperm selection coupled with extensive centrifugations is a highly reliable technique for HIV removal, as it provides lower than reported post-wash positive tests while maintaining high pregnancy rates in assisted reproduction cycles. Despite extensive personnel training and effectiveness of the washing protocol, post-wash HIV test on semen is recommended to identify residual positive samples. PMID- 26995658 TI - Corona cell RNA sequencing from individual oocytes revealed transcripts and pathways linked to euploid oocyte competence and live birth. AB - Corona cells surround the oocyte and maintain a close relationship through transzonal processes and gap junctions, and may be used to assess oocyte competence. In this study, the corona cell transcriptome of individual cumulus oocyte complexes (COCs) was investigated. Isolated corona cells were collected from COCs that developed into euploid blastocysts and were transferred in a subsequent frozen embryo transfer. Ten corona cell samples underwent RNA sequencing to generate unique gene expression profiles. Live birth was compared with negative implantation after the transfer of a euploid blastocyst using bioinformatics and statistical analysis. Individual corona cell samples produced a mean of 21.2 million sequence reads, and 307 differentially expressed transcrpits (P < 0.05; fold change >= 2). Enriched pathway analysis showed Wnt signalling, mitogen-activated protein kinases signalling, focal adhesion and tricarboxylic acid cycle to be affected by implantation outcome. The Wnt/beta catenin signalling pathway, including genes APC, AXIN and GSK3B, were independently validated by real-time quantitative reverse transcription. Individual, corona cell transcriptome was successfully generated using RNA sequencing. Key genes and signalling pathways were identified in association with implantation outcome after the transfer of a euploid blastocyst in a frozen embryo transfer. These data could provide novel biomarkers for the non-invasive assessment of embryo viability. PMID- 26995659 TI - Cytokine-induced STAT1 activation is increased in patients with primary Sjogren's syndrome. AB - Limited data are available regarding the intracellular responses to different cytokines in primary Sjogren's syndrome (pSS). We studied the signal transducer and activator of transcription (STAT) activation profile in response to cytokine stimulations in peripheral blood mononuclear cells (PBMCs) from pSS patients by multicolor flow cytometry. The expression of the suppressors of cytokine signaling (SOCS), and interferon (IFN)-gamma target genes in PBMCs was studied using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The induction of STAT1 phosphorylation in response to stimulation with IFN-alpha, IFN gamma or interleukin (IL)-6 was significantly increased in B cells and monocytes from pSS patients. Accordingly, the STAT1-mediated gene responses were significantly enhanced in PBMCs from pSS patients. Finally, the expression of SOCS1 and SOCS3 mRNA was increased in pSS patients. The results indicate increased sensitivity of immune cells from pSS patients to STAT1-activating signals, and may partly explain the IFN signature observed in pSS. PMID- 26995660 TI - The utility of two dimensional electrophoresis in diagnosis of mucopolysaccharidosis disorders. AB - BACKGROUND: Mucopolysaccharidoses are a group of inherited lysosomal storage disorders consisting of 7 distinct clinical types and numerous subtypes. These are the result of deficiency of certain lysosomal degradative enzymes which are required to breakdown Glycosaminoglycans. The clinical features observed among Mucopolysaccharidoses subtypes show overlapping signs and symptoms with other lysosomal storage disorders and rheumatologic disorders. This makes clinical diagnosis a challenge. With the advent of new therapies, appropriate medical management is possible and hence establishing timely diagnosis has become crucial. METHODS: In this retrospective data analysis, 2 different diagnostic approaches were discussed. The first diagnostic approach involves screening by Glycosaminoglycans' quantification and two-dimensional cellulose acetate electrophoresis and confirmation by enzyme analysis. The second diagnostic approach involves direct enzyme analysis on basis of the clinical suspicion. RESULTS: This first approach seems to be appropriate for the diagnosis of almost all types of Mucopolysaccharidoses. The second approach is found to be more pertinent for type III Mucopolysaccharidosis. CONCLUSIONS: Our retrospective data analysis suggests that urinary Glycosaminoglycans screening followed by enzyme analysis confirmation seems to be rapid and cost effective approach for diagnosing these disorders. PMID- 26995661 TI - Urinary sediment mRNA level of extracellular matrix molecules in adult nephrotic syndrome. AB - BACKGROUND: Glomerular and tubulointerstitial fibrosis play important roles in the progression of chronic kidney disease. We determine whether urinary mRNA levels of extracellular matrix proteins reflect the degree of kidney fibrosis and predict renal function decline in adult nephrotic patients. METHODS: We studied 56 adult nephrotic patients and 20 controls. Urinary mRNA levels of collagen I A1 chain (COL1A1), collagen IV A3 chain (COL4A3), and fibronectin were measured. RESULTS: Urinary sediment mRNA levels of COL1A1 and fibronectin were significantly higher in nephrotic patients as compared to the control, irrespective to the pathological diagnosis. Urinary COL1A1 mRNA level correlates with proteinuria, glomerular and interstitial fibrosis, and inversely with estimated glomerular filtration rate (GFR); urinary fibronectin mRNA level significantly correlates with glomerular and interstitial fibrosis, and inversely with estimated GFR. After 42.4 +/- 12.6 months follow-up, the rate of GFR decline inversely correlates with urinary mRNA level of COL1A1 (r = -0.273, p = 0.044). Multivariate analysis confirmed that urinary COL1A1 mRNA level is an independent predictor of serum creatinine doubling or progressing to end stage renal disease; for each 10-fold increase in urinary COL1A1 mRNA level, there is 15.1% excess in risk (95% confidence interval, 1.9% to 30.4%, p=0.022). CONCLUSIONS: Urinary COL1A1 mRNA level is elevated in nephrotic patients irrespective to the pathological diagnosis, and it correlates with proteinuria, histological scarring, and inversely with renal function. Furthermore, urinary COL1A1 mRNA level predicts renal function loss during follow-up. Our results suggest that urinary COL1A1 mRNA level may be used for risk stratification of adult nephrotic syndrome. PMID- 26995662 TI - The importance of comorbidity and illness severity scores in cardiac arrest research. PMID- 26995663 TI - The optic nerve sheath diameter as a useful tool for early prediction of outcome after cardiac arrest: A prospective pilot study. AB - INTRODUCTION: Optic nerve sheath diameter (ONSD) measurement could detect increased intracranial pressure, and might predict outcome in post-cardiac arrest (CA) patients. We assessed the ability of bedside ONSD ultrasonographic measurement performed within day 1 after CA occurrence to predict in-hospital survival in patients treated with therapeutic hypothermia (TH). METHODS: In two French ICUs, a prospective study included all consecutive patients with CA without traumatic or neurological etiology, successfully resuscitated and TH treated. ONSD measurements were performed on day 1, 2, and 3 (ONSD1, 2, 3 respectively) after return of spontaneous circulation. All records were registered according to Utstein style. RESULTS: ONSD1, 2, 3 were assessed in 36, 21, and 14 patients respectively. 19/36 patients (53%) were discharged alive from hospital, including 14/36 (39%) with favorable neurological outcome (Cerebral Performance Category [CPC] score 1-2). Survivors and non-survivors were similar regarding age, sex, cardiovascular risk factors, location and etiology of CA, simplified acute physiology score II, occurrence of post-CA shock, and clinical parameters collected during ONSD measurements. Median ONSD1 was significantly larger in non-survivors versus survivors (7.2mm [interquartile: 6.8-7.4] versus 6.5mm [interquartile: 6.0-6.8]; p=0.008). After adjustment on predictive factors, ONSD1 was significantly associated with in-hospital mortality (OR 6.3; 95%CI [1.05-40] per mm of ONSD1 above 5.5mm; p=0.03), and CPC score (OR for 1 point increase in CPC score: 3.2; 95%CI [1.2-9.4] per mm of ONSD1 above 5.5mm; p=0.03). ONSD1 was significantly correlated with brain edema assessed by the cerebrum gray matter attenuation to white matter attenuation ratio, measured by the brain computed tomography scan performed on admission in 20 patients (Spearman rho= 0.5, p=0.04). CONCLUSIONS: ONSD seems a promising tool to early assess outcome in post-CA patients treated with TH. PMID- 26995664 TI - Intraosseous access-Of no value in neonatal resuscitation? PMID- 26995666 TI - Caution when comparing different defibrillation waveforms and energies: Jerry Nolan, M.D., Editor-in-Chief, Resuscitation. PMID- 26995665 TI - Reply to: "Caution when comparing different defibrillation waveforms and energies". PMID- 26995667 TI - The association between neighborhood effects and out-of-hospital cardiac arrest outcomes. AB - BACKGROUND: To date, 72% of variability in survival following out-of-hospital cardiac arrest (OHCA) is explained by the Utstein variables. Whether neighborhood factors further influence a return of spontaneous circulation or survival after OHCA is poorly understood. METHODS: We completed a retrospective cohort study of all paramedic-treated OHCA within the City of Toronto's 531 census tracts between 2006 and 2014. Neighborhood variables included the Ontario Marginalization Index a measure of poverty, ethnicity and instability - crime rate and the density of family physicians. Hierarchical logistic regression analysis explored the association between a patient's census tract (neighborhood) characteristics and survival to hospital discharge and a prehospital return of spontaneous circulation (ROSC). Receiver operator characteristics curves measured how the Utstein variables and neighborhood factors discriminate OHCA outcomes. RESULTS: There were 23,067 OHCA during the study period, with 10,097 cases excluded due to obvious death, 896 from an obvious etiology and 2589 cases for other reasons, leaving 9485 patients for analysis. Of the neighborhood variables, only census tracts with a moderate ethnic concentration had an increased likelihood of survival-to-hospital discharge. The Utstein variables accounted for 89.2% of survival and 39.8% of prehospital ROSC. Adding all neighborhood factors to the Utstein model increased discrimination for survival to discharge to 89.8% (p=0.005) and of a prehospital ROSC to 40.8% (p=0.006). CONCLUSIONS: Residential neighborhood factors marginally improve discrimination for outcomes after an OHCA, beyond the Utstein variables. Further research should explore the influence of other currently unmeasured neighborhood factors on OHCA outcomes. PMID- 26995668 TI - Reply to: "Intraosseous access-of no value in neonatal resuscitation?". PMID- 26995669 TI - Traffic-related exposures, constrained restoration, and health in the residential context. AB - Traffic-related exposures may undermine the restorative character of the home, and this may in turn undermine health and residential satisfaction. We addressed this possibility with data for adults residing in a large valley near Innsbruck, Austria (N=572). We joined objective measures of traffic-related sound and air pollutants with reports from door-to-door surveys concerning perceived disturbance from traffic-related exposures, restorative qualities of the living environment, self-perceived health and residential satisfaction. We analyzed these data with successive tests of nested structural equation models, with and without the restorative quality variables. The results suggest that the negative impact of traffic-related exposures on self-perceived health and satisfaction with the living environment involves the constraint of restorative qualities of the living environment, over and above the share traditionally attributed to such exposures viewed as stressors. We discuss theoretical and practical implications of the distinction between environmental stressors and constraints on restoration. PMID- 26995670 TI - Correlation of different spectral lights with biomass accumulation and production of antioxidant secondary metabolites in callus cultures of medicinally important Prunella vulgaris L. AB - Light is one of the key elicitors that directly fluctuates plant developmental processes and biosynthesis of secondary metabolites. In this study, the effects of various spectral lights on biomass accumulation and production of antioxidant secondary metabolites in callus cultures of Prunella vulgaris were investigated. Among different spectral lights, green light induced the maximum callogenic response (95%). Enhanced fresh biomass accumulation was observed in log phases on day-35, when callus cultures were exposed to yellow and violet lights. Yellow light induced maximum biomass accumulation (3.67g/100ml) from leaf explants as compared to control (1.27g/100ml). In contrast, violet lights enhanced biomass accumulation (3.49g/100ml) from petiole explant. Maximum total phenolics content (TPC; 23.9mg/g-DW) and total flavonoids content (TFC; 1.65mg/g-DW) were observed when cultures were grown under blue lights. In contrast, green and yellow lights enhanced total phenolics production (TPP; 112.52g/100ml) and total flavonoids production (TFP; 9.64g/100ml) as compared to control. The calli grown under green, red and blue lights enhanced DPPH-free radical scavenging activity (DFRSA; 91.3%, 93.1% and 93%) than control (56.44%) respectively. The DFRSA was correlated either with TPC and TFC or TPP and TFP. Furthermore, yellow lights enhanced superoxide dismutase (SOD), peroxidase (POD) and protease activities, however, the content of total protein (CTP) was higher in control cultures (186MUg BSAE/mg FW) as compared to spectral lights. These results suggest that the exposure of callus cultures to various spectral lights have shown a key role in biomass accumulation and production of antioxidant secondary metabolites. PMID- 26995672 TI - Inhibitory effects of rosemary (Rosemarinus officinalis L.) essential oil on pathogenicity of irradiated and non-irradiated Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is considered one of the most important opportunistic pathogens, which is responsible for nosocomial infections. The complex pathophysiology of infections associated with P. aeruginosa is due to its ability to grow in a biofilm mass and to produce a large number of virulence factors. This study aimed to investigate the antipseudomonal efficacy of rosemary essential oil (REO) against 25 clinical isolates control and gamma irradiated (at 24.4Gy). Susceptibility testing towards 15 standard antibiotics and REO was carried out using disc diffusion method. The potency of REO on motility, biofilm and pyocyanin production was evaluated. Total protein profile was estimated by SDS polyacrylamide gel electroporesis. REO has showed a broad spectrum of antimicrobial activity compared to the standard antibiotics. According to their high sensitivity to REO, six isolates were chosen for MIC90 with minimum inhibitory concentration (MIC90) values ranged from 5 to 25MUl/ml. REO exerted marked effects on irradiated and non-irradiated tested isolates. The results displayed high significant reduction in biofilm and pyocyanin production. Significant reduction in cell-surface hydrophobicity was observed for some isolates. As for motility, REO altered twitching, swarming and swimming ability of the tested isolates. The ultra structure of bacterial cell results in ruptures of the bacterial cell, leakage of the cytoplasmic components and consequently cell death. Total protein analysis of control, irradiated and irradiated with treatment of REO revealed some changes in protein profile as a result of treatment. CONCLUSION: This study may hasten the application of REO in the treatment and prevention of pseudomonas resistant isolates in nosocomial infections. PMID- 26995671 TI - Direct measurement of singlet oxygen by using a photomultiplier tube-based detection system. AB - The effective dosimetry for photodynamic therapy (PDT) can be specified by direct measurement of singlet oxygen ((1)O2) production. The purpose of this study was to investigate the feasibility of a newly developed photomultiplier tube (PMT) based singlet oxygen detection (SOD) system. The lowest and highest (1)O2 concentrations detectable by the PMT-SOD system were 15nM and 10MUM, respectively. Dose-dependent quenching, by NaN3, of the fluorogenic reaction was observed, which was negatively correlated with the (1)O2 level measured by the PMT-SOD system. The lifetime of (1)O2, as measured by the PMT-SOD system, was found to be lengthened when H2O was replaced with deuterium oxide. (1)O2 photon counts were significantly and dose-dependently correlated with intracellular fluorescence intensity after photosensitizer treatments. In vitro cell viability test and in vivo xenografted-tumor mass shrinkage showed a positive association between PDT-induced cytotoxicity and (1)O2 production concomitantly measured by the PMT-SOD system. It was concluded that the PMT-SOD system is capable of measuring (1)O2 production directly and accurately, demonstrating that this system can be useful in the determination of dosimetry for PDT. PMID- 26995673 TI - Socioeconomic status at birth and risk for first episode psychosis in rural Ireland: Eliminating the features of urbanicity in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). AB - BACKGROUND: There is a paucity of research on the relationship between social environment at birth and risk for psychosis in rural settings. This study examined the relationship between individual- and neighbourhood-level socioeconomic indicators proximal to the time of birth and risk for a first psychotic episode in a rural context using a prospective dataset of unusual epidemiological completeness. METHODS: A matched case-control design was used. 186 cases were identified from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS) and 679 age- and sex-matched controls from the same rural setting were identified and analysed for relationships with individual and neighbourhood-level socioeconomic indicators at the level of Electoral Divisions. RESULTS: While neither the distribution nor the ordinal scale of parental social class differed between cases and controls, logistic regression revealed both parental social class III and increasing level of rurality to be associated (p<=0.05) with reduced risk for affective psychosis. There was a prominent relationship (p<0.001) between lower parental social class and older age at first presentation [mean age at first presentation for all psychoses: social class I, 22.8; social class VI, 44.3]. CONCLUSIONS: These findings indicate modest effects of individual- and neighbourhood-level socioeconomic indicators and risk for psychosis by place at birth within a rural environment. Thus, these factors are not confined to large urban settings and apply across the urban-rural continuum. The substantive finding in relation to age at first presentation may indicate that a gradient of socioeconomic position is influential on delay in presentation to mental health services. PMID- 26995675 TI - Computed tomography: What and how does it measure? AB - The current study provides a comprehensive review about the use and the clinical applications of computed tomography (CT) associated with the in vivo evaluation of the human body composition. The high-resolution CT images allow the accurate separation of the various body compartments at the tissue/organ level including adipose tissue, skeletal muscle, bones and organs. The further ability of the imaging modality to distinguish the cortical from the trabecular bone and the visceral from the susbcutaneous fat is of great value in clinical studies. CT may also give important information about the components of the subcutaneous adipose tissue and the muscle or liver fat infiltration. The efficient determination of the skeletal muscle attenuation and bone mineral density, that related with metabolic disorders, is feasible with the aid of CT data. The area and volume of each human body compartment may be estimated with high accuracy and reproducibility from CT scans. These estimations may be carried out using the methods of manual planimetry, semi-automatic segmentation of the tissue of interest, stereological point-counting approach and geometrical models based either on linear or area measurements. The advantages and disadvantages of the aforementioned methods for the quantification of the human body composition are presented and discussed. PMID- 26995674 TI - Putamen-related regional and network functional deficits in first-episode schizophrenia with auditory verbal hallucinations. AB - OBJECTIVE: Auditory verbal hallucinations (AVHs) are one of the cardinal symptoms of schizophrenia (SZ). Cerebral dysfunction may represent pathophysiological underpinnings behind AVHs in SZ. However, regional and network functional deficits for AVHs in SZ remain to be identified. METHODS: Seventeen medication naive first-episode SZ patients with AVHs, 15 without AVHs, and 19 healthy controls (HCs) were studied using resting-state functional magnetic resonance imaging. We compared the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) among these subjects. Areas with both ALFF and ReHo alterations were used as seeds in functional connectivity (FC) analysis. Then we performed correlation analysis between image measures and symptoms and receiver operating characteristic analysis. RESULTS: One-way analysis of variance showed significant differences of ALFF and ReHo in the bilateral putamen, thereby being used as seeds. SZ patients with AVHs showed decreased ALFF in the left putamen, increased ReHo in the right dorsolateral prefrontal cortex (DLPFC), and increased right putamen-seeded FC with the left DLPFC and Broca's area relative to those without AVHs. Furthermore, the increased strength of the connectivity between the right putamen and left Broca's area correlated with the severity of SZ symptoms. Both patient groups demonstrated hypoconnectivity within frontal/parietal/temporal cortico-striatal-cerebellar networks compared with HCs. CONCLUSION: AVHs in SZ may be caused by abnormal regional function in the putamen and prefrontal cortex, as well as hyperconnectivity between them. The putamen related regional and network functional deficits may reflect imbalance in neuromodulation of AVHs in SZ. Furthermore, dysconnectivity within cortico striatal-cerebellar networks might subserve the pathogenesis of SZ. PMID- 26995676 TI - Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats. AB - Alpha-linolenic acid (C18:3 n-3, ALA) is an essential fatty acid and the metabolic precursor of long-chain polyunsaturated fatty acids (LCPUFA) from the n 3 family with relevant physiological and metabolic roles: eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA). Western diet lacks of suitable intake of n-3 LCPUFA and there are recommendations to increase the dietary supply of such nutrients. Seed oils rich in ALA such as those from rosa mosqueta (Rosa rubiginosa), sacha inchi (Plukenetia volubis) and chia (Salvia hispanica) may constitute an alternative that merits research. This study evaluated hepatic and epididymal accretion and biosynthesis of n-3 LCPUFA, the activity and expression of Delta-5 and Delta-6 desaturase enzymes, the expression and DNA-binding activity of PPAR-alpha and SREBP-1c, oxidative stress parameters and the activity of antioxidative enzymes in rats fed sunflower oil (SFO, 1% ALA) as control group, canola oil (CO, 10% ALA), rosa mosqueta oil (RMO, 33% ALA), sacha inchi oil (SIO, 49% ALA) and chia oil (ChO, 64% ALA) as single lipid source. A larger supply of ALA increased the accretion of n-3 LCPUFA, the activity and expression of desaturases, the antioxidative status, the expression and DNA-binding of PPAR-alpha, the oxidation of fatty acids and the activity of antioxidant enzymes, whereas the expression and DNA-binding activity of SREBP-1c transcription factor and the biosynthetic activity of fatty acids declined. Results showed that oils rich in ALA such as SIO and ChO may trigger metabolic responses in rats such as those produced by n-3 PUFA. PMID- 26995677 TI - Prostaglandin D2 is a novel repressor of IFNgamma induced indoleamine-2,3 dioxygenase via the DP1 receptor and cAMP pathway. AB - Expression of elevated levels of Indoleamine 2,3-dioxygenase (IDO) is well established as a mechanism of cancer induced immunosuppression. Pharmacological inhibition of IDO activity is thus a promising alternative in the treatment of cancer. Previously we demonstrated that cyclooxygenase derived metabolites of arachidonic acid inhibited the interferon-gamma mediated induction of IDO in both THP-1 cells and human monocytes. Here we identified that of the five primary prostanoids produced by COX-1/COX-2, only PGD2 displayed significant repressor activity. PGD2 inhibited IDO activity with an IC50 of 7.2uM in THP-1 cells and 5.2uM in monocytes. PGD2 caused a significant decrease in both IDO mRNA and protein. Using receptor specific agonists, PGD2 was found to act via the DP1 receptor, while the CRTH2 receptor was not involved. A DP1 antagonist significantly reduced the activity of PGD2, while CRTH2 agonists were ineffective. PGD2 increased intracellular cAMP levels and exogenous N(6)-cAMP was also found to be highly inhibitory. The effects of PGD2 via cAMP were blocked by Rp-cAMP indicating involvement of PKA. PGD2 also stimulated CREB phosphorylation, a PKA dependent transcription factor. This is the first report demonstrating that PGD2, a prostanoid typically associated with allergy, can inhibit IDO activity via the DP1/cAMP/PKA/CREB pathway. Our findings suggest that PGD2 and its derivatives may form the basis of novel repressors of IFNgamma-mediated IDO expression. PMID- 26995678 TI - Delivering Prevention Interventions to People Living with HIV in Clinical Care Settings: Results of a Cluster Randomized Trial in Kenya, Namibia, and Tanzania. AB - We conducted a group randomized trial to assess the feasibility and effectiveness of a multi-component, clinic-based HIV prevention intervention for HIV-positive patients attending clinical care in Namibia, Kenya, and Tanzania. Eighteen HIV care and treatment clinics (six per country) were randomly assigned to intervention or control arms. Approximately 200 sexually active clients from each clinic were enrolled and interviewed at baseline and 6- and 12-months post intervention. Mixed model logistic regression with random effects for clinic and participant was used to assess the effectiveness of the intervention. Of 3522 HIV positive patients enrolled, 3034 (86 %) completed a 12-month follow-up interview. Intervention participants were significantly more likely to report receiving provider-delivered messages on disclosure, partner testing, family planning, alcohol reduction, and consistent condom use compared to participants in comparison clinics. Participants in intervention clinics were less likely to report unprotected sex in the past 2 weeks (OR = 0.56, 95 % CI 0.32, 0.99) compared to participants in comparison clinics. In Tanzania, a higher percentage of participants in intervention clinics (17 %) reported using a highly effective method of contraception compared to participants in comparison clinics (10 %, OR = 2.25, 95 % CI 1.24, 4.10). This effect was not observed in Kenya or Namibia. HIV prevention services are feasible to implement as part of routine care and are associated with a self-reported decrease in unprotected sex. Further operational research is needed to identify strategies to address common operational challenges including staff turnover and large patient volumes. PMID- 26995679 TI - Substance Use Patterns of HIV-Infected Russian Women with and Without Hepatitis C Virus Co-infection. AB - Individuals with HIV and hepatitis C virus (HCV) co-infection may experience substance use related health complications. This study characterized substance use patterns between HIV/HCV co-infected and HIV mono-infected Russian women. HIV infected women (N = 247; M age = 30.0) in St. Petersburg, Russia, completed a survey assessing substance use, problematic substance use, and the co-occurrence of substance use and sexual behaviors. Covariate adjusted logistic and linear regression analyses indicated that HIV/HCV co-infected participants (57.1 %) reported more lifetime drug use (e.g., heroin: AOR: 13.2, 95 % CI 4.9, 35.3, p < .001), problem drinking (beta = 1.2, p = .05), substance use problems (beta = 1.3, p = .009), and increased likelihood of past injection drug use (AOR: 26.4, 95 % CI 8.5, 81.9, p < .001) relative to HIV mono-infected individuals. HIV/HCV co-infection was prevalent and associated with increased substance use and problematic drug use. Findings highlight the need for ongoing substance use and HIV/HCV risk behavior assessment and treatment among HIV/HCV co-infected Russian women. PMID- 26995680 TI - Should I stay or should I go? Fitness costs and benefits of prolonged parent offspring and sibling-sibling associations in an Arctic-nesting goose population. AB - Theory predicts persistence of long-term family relationships in vertebrates will occur until perceived fitness costs exceed benefits to either parents or offspring. We examined whether increased breeding probability and survival were associated with prolonged parent-offspring and sibling-sibling relationships in a long-lived Arctic migrant herbivore, the Greenland white-fronted goose (Anser albifrons flavirostris). Although offspring associated with parents for 1-13 years, 79 % of these associations lasted two or less years. Only 65 (9.9 %) of the 656 marked offspring bred once in their lifetime, and just 16 (2.4 %) bred twice or more. The probability of birds with siblings breeding successfully in a subsequent year was credibly greater than that of independent birds at ages 5, 6, and 7. Survival of offspring with parents was credibly greater than that of independent/nonbreeder birds at all possible ages (i.e., ages 2-7+). A cost benefit matrix model utilizing breeding and survival probabilities showed that staying with family groups was favored over leaving until age 3, after which there were no credible differences between staying and leaving strategies until the oldest ages, when leaving family groups was favored. Thus, most birds in this study either departed family groups early (e.g., at age 2, when the "stay" strategy was favored) or as predicted by our cost-benefit model (i.e., at age 3). Although extended family associations are a feature of this population, we contend that the survival benefits are not sufficient enough to yield clear fitness benefits, and associations only persist because parents and offspring mutually benefit from their persistence. PMID- 26995681 TI - Special issue: Radioactive contamination in forest ecosystems: From Chernobyl to Fukushima. PMID- 26995682 TI - Formaldehyde as a carbon and electron shuttle between autotroph and heterotroph populations in acidic hydrothermal vents of Norris Geyser Basin, Yellowstone National Park. AB - The Norris Geyser Basin in Yellowstone National Park contains a large number of hydrothermal systems, which host microbial populations supported by primary productivity associated with a suite of chemolithotrophic metabolisms. We demonstrate that Metallosphaera yellowstonensis MK1, a facultative autotrophic archaeon isolated from a hyperthermal acidic hydrous ferric oxide (HFO) spring in Norris Geyser Basin, excretes formaldehyde during autotrophic growth. To determine the fate of formaldehyde in this low organic carbon environment, we incubated native microbial mat (containing M. yellowstonensis) from a HFO spring with (13)C-formaldehyde. Isotopic analysis of incubation-derived CO2 and biomass showed that formaldehyde was both oxidized and assimilated by members of the community. Autotrophy, formaldehyde oxidation, and formaldehyde assimilation displayed different sensitivities to chemical inhibitors, suggesting that distinct sub-populations in the mat selectively perform these functions. Our results demonstrate that electrons originally resulting from iron oxidation can energetically fuel autotrophic carbon fixation and associated formaldehyde excretion, and that formaldehyde is both oxidized and assimilated by different organisms within the native microbial community. Thus, formaldehyde can effectively act as a carbon and electron shuttle connecting the autotrophic, iron oxidizing members with associated heterotrophic members in the HFO community. PMID- 26995683 TI - Microbial community structure analysis of a benzoate-degrading halophilic archaeal enrichment. AB - A benzoate-degrading archaeal enrichment was developed using sediment samples from Rozel Point at Great Salt Lake, UT. The enrichment degraded benzoate as the sole carbon source at salinity ranging from 2.0 to 5.0 M NaCl with highest rate of degradation observed at 4.0 M. The enrichment was also tested for its ability to grow on other aromatic compounds such as 4-hydroxybenzoic acid (4-HBA), gentisic acid, protocatechuic acid (PCA), catechol, benzene and toluene as the sole sources of carbon and energy. Of these, the culture only utilized 4-HBA as the carbon source. To determine the initial steps in benzoate degradation pathway, a survey of ring-oxidizing and ring-cleaving genes was performed using degenerate PCR primers. Results showed the presence of 4-hydroxybenzoate 3 monooxygenase (4-HBMO) and protocatechuate 3, 4-dioxygenase (3,4-PCA) genes suggesting that the archaeal enrichment might degrade benzoate to 4-HBA that is further converted to PCA by 4-HBMO and, thus, formed PCA would undergo ring cleavage by 3,4-PCA to form intermediates that enter the Krebs cycle. Small subunit rRNA gene-based diversity survey revealed that the enrichment consisted entirely of class Halobacteria members belonging to the genera Halopenitus, Halosarcina, Natronomonas, Halosimplex, Halorubrum, Salinarchaeum and Haloterrigena. Of these, Halopenitus was the dominant group accounting for almost 91 % of the total sequences suggesting their potential role in degrading oxygenated aromatic compounds at extreme salinity. PMID- 26995684 TI - What Can Influence Iranian Suicide Attempters to Go Through the Process of Non Fatal Suicide Act Once Again? A Preliminary Report. AB - The thrust of this study was to examine some of the psycho-social risk factors for the recurrence of non-fatal suicide attempt in a sample of 1121 inmates admitted between April 2012 to June 2013 at the toxicology emergency ward, Noor Medical Centre, Isfahan, Iran. Out of the total participants, 240 of them reported history of suicide attempt and assumed the status of case group. The remaining 881 patients were admitted first their attempt and constituted the control group. Cases were compared to the controls with respect to select demographic features (i.e. age, sex, education, occupation, marital status, type of residence, and locale), current suicide attempt method, family history of suicide and drug abuse, history of psychiatric disorder, physical ailment and physical disability, substance abuse and alcohol use, psychiatric diagnosis, and recent life hassles (i.e. interpersonal, occupational, financial, medical, and home affairs). We used a structured interview schedule to interview the participants. Psychiatric diagnosis was based on the DSM-IV criteria. Data were computer analyzed using SPSS.21 and administering statistical analysis including Chi Square, t-student, and logistic regression. Demographic risk factors for recurrence of suicide attempts at the univariate level included occupational status [Crud odds Ratio (COR) = 0.53] and type of residence (COR = 1.40). Medical and psychiatric risk factors at the univariate level included substance abuse (COR = 1.97), physical ailment (COR = 1.76), alcohol use (COR = 1.84), psychiatric disorder (COR = 3.69), and history of suicide in the family of origin (COR = 1.86). Recent life hassles risk factors at the univariate level included financial constraints (COR = 1.46) and medical emergencies (COR = 3.48). A multivariate logistic regression model identified five variables (i.e. substance abuse, alcohol use, psychiatric illness, suicide in family, and medical emergencies) that were statistically associated with an increased risk for recurrence of nonfatal suicide attempt. The model predicted chances of repeating suicide attempt correctly 79 % of the time. These observations indicate that people who report to the toxicology emergency ward for nonfatal suicide not only need immediate relief but also careful psychiatric and social assessments which subsequently may lead to psychiatric admission and comprehensive community interventions. PMID- 26995685 TI - [Outcome of triplet pregnancies managed for twin-to-twin transfusion syndrome: A single center experience]. AB - OBJECTIVES: Study the outcomes of triplet pregnancies (GGG) complicated with twin to-twin transfusion syndrome (TTTS) treated with laser fetoscopy. METHODS: Retrospective study of interventions, outcomes and perinatal follow-up of GGG treated for TTS. RESULTS: Between 2002 and 2013, 25 GGG complicated by TTTS were seen in our center, 20 dichorionic and 5 monochorionic. The mean gestational age (GA) at diagnosis of TTTS was 19.7 GW (+/-2.4) with 2, 4, 16 and 1 pregnancies at Quintero's stage I, II, III and V, respectively. They had a fetoscopy at an average GA of 19 GW and 6 days. There were 3 (13.0%) late miscarriages. The average GA at delivery was of 29.6 GW overall (26.3 GW and 31.1 GW in monochorionic and dichorionic pregnancies respectively). The overall fetal survival rate was 57.97% (40% and 66.7% in the group of monochorionic dichorionic pregnancies, respectively). However, neonatal mortality (<28 days) is 17.5%. CONCLUSION: GGG operated by fetoscopy for TTTS have a survival rate of three, at least 2 and at least 1 fetus of 21.7%, 69.6% and 82.6% respectively. The overall fetal survival rate is 59.97%. There is a tendency for better survival rates in dichorionic GGG compared to monochorionic GGG (P=0.079). PMID- 26995686 TI - A novel Xq22.1 deletion in a male with multiple congenital abnormalities and respiratory failure. AB - Here we report the first male case of a novel Xq22.1 deletion. An 8-week-old boy with multiple congenital abnormalities and respiratory failure was referred to the Mayo Clinic Cytogenetics laboratory for testing. Chromosomal microarray analysis identified a novel 1.1 Mb deletion at Xq22.1. A similar deletion has only been described once in the literature in a female patient and her mother; both have intellectual disability and dysmorphic facial features. In addition, the mother had a son who died at 15 days due to breathing failure. Recently, a mouse model revealed that a 0.35 Mb sub-region, containing 4 genes, is sufficient to cause majority of the Xq22.1 deletion phenotypes. The deleted intervals in our male patient and the female patients contain 15 common genes, including the four described in the 0.35 Mb sub-region. Male mice with deletion of the 0.35 Mb sub region died perinatally from respiratory failure due to pulmonary hypoplasia, consistent with the breathing problem and potential neonatal fatality in male patients. The phenotypes of the mouse models and the patients are strikingly similar; therefore, the deletion of these five genes (ARMCX5, ARMCX5-GPRASP2, GPRASP1, GPRASP2, and BHLHB9) is likely responsible for the novel Xq22.1 deletion syndrome. PMID- 26995687 TI - How fisheries management can benefit from genomics? AB - Fisheries genomics is an emerging field that advocates the application of genomic tools to address questions in fisheries management. Genomic approaches bring a new paradigm for fisheries management by making it possible to integrate adaptive diversity to understand fundamental aspects of fisheries resources. Hence, this review is focused on the relevance of genomic approaches to solve fisheries specific questions. Particularly the detection of adaptive diversity (outlier loci) provides unprecedented opportunity to understand bio-complexity, increased power to trace processed sample origin to allow enforcement and the potential to understand the genetic basis of micro-evolutionary effects of fisheries-induced evolution and climate change. The understanding of adaptive diversity patterns will be the cornerstone of the future links between fisheries and genomics. These studies will help stakeholders anticipate the potential effects of fishing or climate change on the resilience of fisheries stocks; consequently, in the near future, fisheries sciences might integrate evolutionary principles with fisheries management. PMID- 26995688 TI - Randomized trial comparing a side-port needle and standard needle for EUS-guided histology of pancreatic lesions. AB - BACKGROUND AND AIMS: A side-port needle has been developed to improve diagnostic accuracy by obtaining more cellular material during EUS-guided FNA (EUS-FNA). We compared the accuracy rate of histology and the quality of histologic specimens from 22-gauge (G) side-port and standard needles for EUS-FNA of a solid pancreatic mass in a multicenter, prospective, randomized control trial. METHODS: Between January 2013 and September 2013, 160 consecutive patients with a suspected solid pancreatic mass at 5 tertiary referral centers were enrolled. Patients were randomized to the 22G side-port needle or 22G standard needle group. The primary endpoint was the diagnostic accuracy of histology. Secondary endpoints were the quality of the histologic specimen (quantity of tissue, degree of GI contamination, and amount of blood). RESULTS: An analysis of 154 patients (side-port, 76, vs standard, 78) was performed. Six patients were excluded because of no pancreatic mass on EUS. There was no significant difference in the rate of diagnostic accuracy of histology (side-port, 87% [66/76], vs standard, 82% [64/78]; P = .51). Samples that enabled histologic interpretation were obtained in 64% (47/73) and 43% (33/77) of patients from the side-port and standard groups, respectively (P = .009). No significant difference was seen in the degree of GI contamination and amount of blood between groups. CONCLUSIONS: There was no significant difference in the accuracy rate of histology between needle types. The side-port needle was superior to the standard needle in terms of obtaining samples that enabled histologic interpretation. PMID- 26995689 TI - Histologic intestinal metaplasia and endoscopic atrophy are predictors of gastric cancer development after Helicobacter pylori eradication. AB - BACKGROUND AND AIMS: Helicobacter pylori eradication therapy is effective at reducing the incidence of gastric cancer; however, gastric cancer still develops after eradication. We conducted a cohort study to elucidate the risk factors for gastric cancer development after successful H pylori eradication therapy. METHODS: From June 1998 to December 2012 we assessed histologic and endoscopic findings of gastritis and performed H pylori eradication therapy in 748 patients without a history of gastric cancer. Patients were classified according to the distribution of intestinal metaplasia (IM) as follows: no IM (IM group A), IM in the antrum only (IM group B), and IM in the corpus (IM group C). We assessed atrophy endoscopically according to the Kimura-Takemoto classification system. Gastric cancer incidence was assessed. RESULTS: A total of 573 patients underwent follow-up endoscopy; the mean duration of follow-up was 6.2 +/- 4.8 years. Gastric cancer developed in 21 (20 intestinal type). The cumulative 5-year incidences of gastric cancer were 3.2% overall; 1.5%, 5.3%, and 9.8% in IM groups A, B, and C; and 0.7%, 1.9%, and 10% in the none/mild, moderate, and severe endoscopic atrophy groups, respectively. Compared with IM group A, the hazard ratio for IM group B was 3.6 (95% confidence interval [CI], 1.2-11), and that for IM group C was 3.7 (95% CI, 1.1-12). Compared with the none/mild endoscopic atrophy group, the hazard ratio for severe atrophy was 9.3 (95% CI, 1.7-174). CONCLUSIONS: Patients with histologic IM or severe endoscopic atrophy were at increased risk of gastric cancer development after H pylori eradication. PMID- 26995691 TI - Canadian Physical Activity Clinical Practice Guidelines: Running on Empty? PMID- 26995690 TI - Digital, single-operator cholangiopancreatoscopy in the diagnosis and management of pancreatobiliary disorders: a multicenter clinical experience (with video). AB - BACKGROUND AND AIMS: Digital cholangioscopes provide higher-resolution imaging of the pancreatobiliary tract compared with fiberoptic instruments. The role of a new, digital, single-operator cholangiopancreatoscopy (SOC) system for diagnosis and treatment of pancreatobiliary disorders in clinical practice is not known. METHODS: We performed a multicenter, observational study of 105 consecutive patients with suspected pancreatobiliary disorders. The main outcome measures were (1) sensitivity and specificity of SOC visual appearance and biopsies in the diagnosis of indeterminate biliary strictures and (2) achieving complete duct clearance in patients with biliary or pancreatic duct stones. RESULTS: A total of 98 cholangioscopy and 7 pancreatoscopy procedures were performed in 105 patients. Superior views of the ductal lumen and mucosa were obtained in all 44 patients with indeterminate biliary strictures. Among the 44 patients who underwent SOC guided biopsies, the specimen was adequate for histologic evaluation in 43 patients (97.7%). The sensitivity and specificity of SOC visual impression for diagnosis of malignancy was 90% (95% confidence interval [CI], 69.9%-97.2%) and 95.8% (95% CI, 79.8%-99.3%), respectively. The sensitivity and specificity of SOC guided biopsies for diagnosis of malignancy was 85% (95% CI, 64.0%-94.8%) and 100% (95% CI, 86.2%-100%). In patients with biliary or pancreatic duct stones (N = 36), complete duct clearance with stone removal in 1 session was accomplished in 86.1% of patients (31/36). Three patients (2.9%) experienced SOC-related adverse events that included cholangitis in 2 patients and postprocedure pancreatitis in 1 patient. CONCLUSIONS: SOC has become an integral part of the ERCP armamentarium and has high accuracy in the evaluation of indeterminate biliary strictures. Complete stone clearance was achieved in all but 1 patient with challenging biliary or pancreatic duct stones. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01815619.). PMID- 26995692 TI - Reflections on Physical Activity and Health: What Should We Recommend? AB - The health benefits of regular physical activity are irrefutable; virtually everyone can benefit from being active. The evidence is overwhelming with risk reductions of at least 20%-30% for more than 25 chronic medical conditions and premature mortality. Even higher risk reductions (ie, >= 50%) are observed when objective measures of physical fitness are taken. International physical activity guidelines generally recommend 150 minutes per week of moderate- to vigorous intensity physical activity. A critical review of the literature indicates that half of this volume of physical activity might lead to marked health benefits. There is compelling evidence to support health promotion strategies that emphasize that health benefits can be accrued at a lower volume and/or intensity of physical activity. Public health policies are needed that reduce the barriers to physical activity participation such that everyone can reap the benefits of physical activity. It is also important to highlight that sedentary time (particularly sitting time) carries independent health risks. The simple message of "move more and sit less" likely is more understandable by contemporary society and is formed on the basis of a strong body of evidence. For practitioners who work directly with clients, it is recommended that an individualized prescription (dosage) that takes into consideration the unique characteristics and needs of the client is provided. Physical activity or exercise promotion should not be done in isolation; it should be part of an integrated approach to enhance healthy lifestyle behaviours. PMID- 26995693 TI - Allogeneic Stem Cell Transplantation for Patients with T315I BCR-ABL Mutated Chronic Myeloid Leukemia. AB - Allogeneic stem cell transplantation (SCT) is currently the only curative treatment option for chronic myeloid leukemia (CML) patients with BCR-ABL T315I mutations. We report the outcome of SCT in 22 patients with T315I(+) CML, most (n = 16) from haploidentical family donors (HID-SCT). At the time the mutation was detected, 8 patients were in the chronic phase (CP), 7 in the accelerated phase (AP), and 7 in the blast phase (BP). At the time of SCT 7 were in the CP, 8 in the AP or returning to the CP post-AP (AP/AP-CPn), and 7 in the BP or returning to CP post-BP (BP/BP-CPn). The cumulative incidence of grades III to IV acute graft-versus-host disease was 9.1%. Chronic graft-versus-host disease was observed in 60.0% of patients, including 25.0% who suffered from severe disease. Four patients died of transplant-related complications at a median interval from SCT of 16.3 months. The estimated 2-year leukemia-free survival rate was 80.0%, 72.9%, and 0% in CP, AP/AP-CPn and BP/BP-CPn groups at the time of SCT, respectively. After a median follow-up of 17.3 months from SCT, 14 patients are alive, including 13 in complete molecular response and 1 with an extramedullary relapse. In conclusion, HID-SCT is a potentially curative treatment for T315I + CML patients. For patients in CP/AP, immediate SCT might result in promising survival. The outcome of patients in BP with T315I(+) mutation remains very poor. PMID- 26995694 TI - Association of Socioeconomic Status with Outcomes of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma. AB - Autologous hematopoietic cell transplantation (AHCT) is standard therapy for eligible patients with multiple myeloma. Health care disparities can influence transplantation outcomes. However, the association of socioeconomic status (SES), a major indicator of health care disparities, with outcomes in patients with myeloma after AHCT has not been previously described. We analyzed 346 consecutive AHCT recipients with myeloma who underwent transplantation between 2003 and 2013 in this retrospective cohort study. Zip code of residence at the time of AHCT was obtained to assess annual household income based on 2010 US census data (median, $49,054; range, $16,546 to $127,313). SES groups were divided into < $45,000 (low; n = 120), $45,000 to $60,000 (middle; n = 116), and > $60,000 (high; n = 110). The low-income cohort had smallest portion of Caucasians (69% versus 89% versus 91%); otherwise, patient, disease, and transplantation characteristics were comparable among cohorts or different without significant patterns found. Median follow-up was 49 months. There was no difference among SES groups in overall survival, progression-free survival, nonrelapse mortality, or relapse in univariate and multivariable analysis. Similarly, SES was not associated with survival in a subset analysis of 303 patients who had survived for 1 year after transplantation. PMID- 26995695 TI - Targeting Leishmania major parasite with peptides derived from a combinatorial phage display library. AB - Cutaneous leishmaniasis (CL) is a global problem caused by intracellular protozoan pathogens of the genus Leishmania for which there are no suitable vaccine or chemotherapy options. Thus, de novo identification of small molecules binding to the Leishmania parasites by direct screening is a promising and appropriate alternative strategy for the development of new drugs. In this study, we used a random linear hexapeptide library fused to the gene III protein of M13 filamentous bacteriophage to select binding peptides to metacyclic promastigotes from a highly virulent strain of Leishmania major (Zymodeme MON-25; MHOM/TN/94/GLC94). After four rounds of stringent selection and amplification, polyclonal and monoclonal phage-peptides directed against L. major metacyclic promastigotes were assessed by ELISA, and the optimal phage-peptides were grown individually and characterized for binding to L. major by monoclonal phage ELISA. The DNA of 42 phage-peptides clones was amplified by PCR, sequenced, and their amino acid sequences deduced. Six different peptide sequences were obtained with frequencies of occurrence ranging from 2.3% to 85.7%. The biological effect of the peptides was assessed in vitro on human monocytes infected with L. major metacyclic promastigotes, and in vivo on susceptible parasite-infected BALB/c mice. The development of cutaneous lesions in the right hind footpads of infected mice after 13 weeks post-infection showed a protection rate of 81.94% with the injected peptide P2. Moreover, Western blots revealed that the P2 peptide interacted with the major surface protease gp63, a protein of 63kDa molecular weight. Moreover, bioinformatics were used to predict the interaction between peptides and the major surface molecule of the L. major. The molecular docking showed that the P2 peptide has the minimum interaction energy and maximum shape complimentarity with the L. major gp63 active site. Our study demonstrated that the P2 peptide occurs at high frequency during the screening procedure, best inhibits L. major growth kinetics in vitro, and reduces cutaneous lesions in BALB/c mice, thus showing great promise in the development of new therapeutic molecules. PMID- 26995696 TI - Haemoproteus erythrogravidus n. sp. (Haemosporida, Haemoproteidae): Description and molecular characterization of a widespread blood parasite of birds in South America. AB - The great diversity of birds and ecosystems in the Andean mountains has been understudied in terms of their parasite species. We describe a new Haemoproteus parasite, H. (Parahaemoproteus) erythrogravidus infecting Zonotrichia capensis (Rufous-Collared Sparrow) in South America. The description of this blood parasite species is supported by morphological and molecular data based on a fragment of cytochrome b gene (cyt b) and complete mitochondrial genome sequences. The new species is closely related to H. (Parahaemoproteus) coatneyi, and it can be readily distinguished from the latter parasite due to morphology of its blood stages, particularly 1) the formation of a marked protrusion on envelope of infected erythrocytes by the majority of developing gametocytes, a feature which is unique for this Haemoproteus species and 2) the extremely attenuated width of the growing dumbbell-shaped macro- and microgametocytes. Additionally, Haemoproteus erythrogravidus is shown to be a monophyletic taxon that diverges from Haemoproteus coatneyi at the molecular level. We provide the complete mitochondrial DNA genome for both H. coatneyi and H. erythrogravidus. Molecular and morphological evidences indicate that H. erythrogravidus is present in Ecuador and Colombia, and genetic lineages with 100% of identity for the cyt b gene were reported in Chile, Peru, and Venezuela. Our study also indicates that H. erythrogravidus and H. coatneyi are sympatric sister taxa sharing Z. capensis as a host species across its distribution, which could be the result of sympatric speciation or complex biogeographic processes. Further studies on the distribution and evolutionary history of Z. capensis and its parasites H. erythrogravidus and H. coatneyi insight for our better understanding of the factors and dynamics driving parasite speciation. PMID- 26995698 TI - Executive Function in Patients with Congenital Heart Disease: Only the Tip of the Iceberg? PMID- 26995697 TI - Targeting Fat: Mechanisms of Protein Localization to Lipid Droplets. AB - How proteins specifically localize to the phospholipid monolayer surface of lipid droplets (LDs) is being unraveled. We review here the major known pathways of protein targeting to LDs and suggest a classification framework based on the localization origin for the protein. Class I proteins often have a membrane embedded, hydrophobic 'hairpin' motif, and access LDs from the endoplasmic reticulum (ER) either during LD formation or after formation via ER-LD membrane bridges. Class II proteins access the LD surface from the cytosol and bind through amphipathic helices or other hydrophobic domains. Other proteins require lipid modifications or protein-protein interactions to bind to LDs. We summarize knowledge for targeting and removal of the different classes, and highlight areas needing investigation. PMID- 26995701 TI - Thyroxine-Based Screening for Congenital Hypothyroidism in Neonates with Down Syndrome. AB - OBJECTIVE: To ascertain whether thyroxine (T4)-based screening programs for congenital hypothyroidism (initial measurement of total T4 [tT4] followed by thyroid stimulating hormone [TSH] measurement in patients with tT4 <10th percentile) identifies congenital hypothyroidism in all neonates with Down syndrome. STUDY DESIGN: Retrospective cohort study of 159 neonates with Down syndrome, born during the period 1998-2007 were included. Screening test results were compared with those of the general population. All primary care physicians of these infants were contacted and infants' thyroid status verified. RESULTS: tT4 concentrations in children with Down syndrome were significantly lower, and TSH higher than those in the general population; tT4 concentrations did not correlate with screening TSH concentrations. Twenty children with Down syndrome were treated with L-thyroxin within the first month of life although only 10 babies had been identified by the routine screening test. CONCLUSIONS: T4-based screening does not identify many cases of congenital hypothyroidism in neonates with Down syndrome. We recommend that neonates with Down syndrome be screened by simultaneous measurements of both tT4 and TSH. PMID- 26995700 TI - Birth Size, Early Life Weight Gain, and Midchildhood Cardiometabolic Health. AB - OBJECTIVE: To examine associations of birth size and weight gain during 4 early life age intervals with midchildhood adiposity and metabolic profile and to evaluate for an interaction between birth size and early-life weight gain. STUDY DESIGN: Using data from 963 participants of Project Viva, a US prebirth cohort, we used multivariable linear regression to examine relations of birth size (tertiles of birthweight-for-gestational-age z-score) and weight gain (body mass index z-score [BMIZ] change) during 4 age intervals (birth-6 months, 6 months-1 year, 1-2 years, 2-3 years) with body composition and metabolic biomarkers during midchildhood (6.6-10.7 years). RESULTS: After accounting for confounders and previous growth, greater BMIZ change during all 4 age intervals corresponded with higher midchildhood adiposity, with larger effect sizes for later (1-2 years and 2-3 years) vs earlier (birth-6 months and 6 months-1 year) time frames. We observed effect modification by birth size for the birth-6 months and 6 months-1 year intervals. Greater birth-6 months BMIZ change was associated with higher overall adiposity (0.40 [95% CI 0.29, 0.51] kg dual x-ray absorptiometry total fat mass per z-score) among children in the highest birth size tertile. Similar associations were observed for central adiposity. Each increment in 6 months-1 year BMIZ change corresponded with 0.55 (0.05, 1.05) units higher homeostatic model assessment of insulin resistance and 2.68 (0.96, 4.40) ng/mL higher leptin among the smallest infants. CONCLUSIONS: BMIZ gain after 1 year is associated with greater midchildhood adiposity regardless of birth size, whereas the long term influence of weight gain during the first postnatal year may depend on size at birth. Future studies are warranted to validate findings and examine relations with conventional birth size cut-offs. PMID- 26995699 TI - Intercenter Cost Variation for Perinatal Hypoxic-Ischemic Encephalopathy in the Era of Therapeutic Hypothermia. AB - OBJECTIVE: To quantify intercenter cost variation for perinatal hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia across children's hospitals. STUDY DESIGN: Prospectively collected data from the Children's Hospitals Neonatal Database and Pediatric Health Information Systems were linked to evaluate intercenter cost variation in total hospitalization costs after adjusting for HIE severity, mortality, length of stay, use of extracorporeal support or nitric oxide, and ventilator days. Secondarily, costs for intensive care unit bed, electroencephalography (EEG), and laboratory and neuroimaging testing were also evaluated. Costs were contextualized by frequency of favorable (survival with normal magnetic resonance imaging) and adverse (death or need for gastric tube feedings at discharge) outcomes to identify centers with relative low costs and favorable outcomes. RESULTS: Of the 822 infants with HIE treated with therapeutic hypothermia at 19 regional neonatal intensive care units, 704 (86%) survived to discharge. The median cost/case for survivors was $58 552 (IQR $32 476-$130 203) and nonsurvivors $29 760 (IQR $16 897-$61 399). Adjusting for illness severity and select interventions, intercenter differences explained 29% of the variation in total hospitalization costs. The widest cost variability across centers was EEG use, although low cost and favorable outcome centers ranked higher with regards to EEG costs. CONCLUSIONS: There is marked intercenter cost variation associated with treating HIE across regional children's hospitals. Our investigation may help establish references for cost and enhance quality improvement and resource utilization projects related to HIE. PMID- 26995702 TI - A Comparison of Prenatal and Postnatal Models to Predict Outcomes at the Border of Viability. AB - OBJECTIVE: To compare the accuracy of a prenatal outcomes calculator developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) with a postnatal neonatal intensive care unit (NICU) prediction model for mechanically ventilated infants. STUDY DESIGN: Over a 3-year period, we identified 89 ventilated infants born in our NICU between 23 and 25 weeks gestation. We retrospectively determined the predicted morbidity and mortality for each infant using the prenatal NICHD Neonatal Research Network: Extremely Preterm Birth Outcome Data website calculator. For our postnatal prediction model, we assessed 2 factors while each infant was on mechanical ventilation: daily intuitions about whether the infant would die before NICU discharge and abnormal head ultrasound. We compared the prenatal and postnatal models for predicting outcomes at 2 years adjusted age. RESULTS: Of the 89 infants, 54 (61%) died or had neurologic developmental impairment (NDI) and 35 (39%) survived without NDI. The NICHD Neonatal Research Network: Extremely Preterm Birth Outcome Data website calculator predicted that 61 (69%) would either die or have NDI and that 28 (31%) would survive without NDI. Positive clinicians' intuitions about survival combined with normal head ultrasound scan results during a trial of therapy in the NICU predicted a 30% greater chance for survival without NDI than the prenatal tool. CONCLUSIONS: When infants at the border of viability are born and cared for in the NICU, they move from predictions for population-based outcomes into predictions based on individual trajectories and outcomes. A clinical trial of therapy provides additional prognostic information that can guide parental decisions made near the time of birth. PMID- 26995703 TI - Strong Additional Effect of a Second Varicella Vaccine Dose in Children in Germany, 2009-2014. AB - OBJECTIVES: Vaccine effectiveness (VE) of 1 and 2 varicella vaccine doses in children aged 1-4 years in Germany was evaluated to determine the additional effect of a second dose recommended at least 4 weeks after the first dose and before the second birthday. STUDY DESIGN: To estimate the VE, the proportion of cases vaccinated was compared with the proportion of the population vaccinated using nationwide sentinel surveillance data from 2009-2014 and health insurance claims data covering the period January 2009-March 2014, respectively. A general linear model was used to estimate the OR of vaccination in the cases and the population and the corresponding CIs to observe the stability of the VE estimates over time, and to assess the incremental effectiveness of a second dose. RESULTS: The overall VE after 1 dose was 86.6% (95% CI: 85.2-87.9), ranging between 94.6% (95% CI: 87.9-97.6) in the first quarter of 2011 and 50.3% (95% CI: 7.3-73.4) in the third quarter of 2013. The overall VE after 2 doses was 97.3% (95% CI: 97.0 97.6), ranging between 99.5% (95% CI: 97.8-99.9) in the second quarter of 2009 and 91.3% (95% CI: 85.7-94.8) in the third quarter of 2013. The incremental VE of 2 doses was 84.6% (95% CI: 81.7-86.9). CONCLUSIONS: The substantially higher VE of 2 varicella vaccine doses compared with 1 dose in young children and the strong additional effect of the second dose support the public health relevance of a 2-dose schedule and the success of the early second vaccine dose. PMID- 26995705 TI - AHS Members' Choice Award for the Best Headache Article. PMID- 26995704 TI - The effect of intrathecal baclofen treatment on activities of daily life in children and young adults with cerebral palsy and progressive neurological disorders. AB - INTRODUCTION: Intrathecal baclofen (ITB) treatment is applied in patients with spastic cerebral palsy (SCP), dystonic cerebral palsy (DCP) and progressive neurological disease (PND). Our aim was to investigate whether ITB treatment has a different effect on activities of daily life (ADL) in these groups. METHOD: A retrospective and cross-sectional survey was conducted using a questionnaire to assess the qualitative effect of ITB (Likert scale) on different domains of functioning (mobility, personal care, communication, comfort) and satisfaction with the results. Groups were compared using non-parametric statistics. RESULTS: Questionnaires were completed for 68 patients (39 SCP, 13 DCP, 16 PND). Satisfaction scores were relatively high in all groups (7-8) and the positive effect on personal care and communication was similar in all groups. The PND group had the shortest follow-up and scored significantly less favourably for the effect on mobility and comfort. DISCUSSION: This is the first study to show that ITB treatment has similar effects on personal care and communication in stable and progressive neurological disease. The decrease in mobility in the PND group is likely due to the progressive nature of the disease. The different effect on comfort between groups is mainly due to the smaller effect on startles in the PND group. PMID- 26995706 TI - Ergot Use and Overuse: A Pharmacoepidemiology Retrospective Cohort Study. AB - OBJECTIVE: The objective of this study was to estimate and to characterize the actual patterns of ergot use and overuse in France using a drug reimbursement database. METHODS: We included all people covered by the French General Health Insurance System (GHIS) from the Provence-Alpes-Cote-d'Azur (PACA) and Corsica administrative areas who had at least one prescription of ergot between May 2010 and December 2011. All prescriptions of ergots, migraine prophylactic treatment, and psychotropic medications were extracted from the GHIS database. We defined occasional ergot users (<3 months of prescription) and regular ergot users (>3 months of prescription). Among regular ergot users, we identified overusers and nonoverusers. RESULTS: We included 4358 patients who had at least one prescription of ergots (oral ergotamine tartrate, dihydroergotamine mesilate nasal spray, intravenous dihydroergotamine mesilate). Among ergot overusers, a large majority of patients had ergotamine tartrate overuse. The proportion of ergotamine tartrate overusers is maximum after 55 years. Compared with regular users, overusers use more frequently a prophylactic treatment (93/165 [56.4%] versus 398/1057, OR = 2.15, P < .001), antidepressants (72/165 [43.6%] versus 326/1057 [30.8%] OR = 1.79, P < .001), benzodiazepines (111/165 [67.3%] versus 613/1057 [58.0%], OR = 1.50, P < .001), weak opioids (95/165 [57.6%] versus 463/1057 [43.8], OR = 1.77, P < .001) and strong opioids (13/165 [7.9%] versus 24/1057 [2.3%], OR = 3.86, P < .001). The coexistence of ergot consumption and triptan overuse, and the possibility of both triptan and ergot overuse was described; triptan overusers were more described in ergotamine overusers than in nonoverusers. CONCLUSIONS: This work outlines a high prevalence of ergotamine tartrate overuse (11.1%). As ergotamine tartrate users are mostly aged more than 55 years, an evaluation of ergotamine cardiovascular risk profile is necessary in the elderly population. PMID- 26995707 TI - Migraine, Chronic Vasculopathies, and Spreading Depolarization. PMID- 26995708 TI - Erratum. PMID- 26995710 TI - Listen to the patient: challenges in the evaluation of the risk of suicidal behaviour. PMID- 26995711 TI - Cycle time influences the development of muscle fatigue at low to moderate levels of intermittent muscle contraction. AB - Localized muscle fatigue (LMF) during a repetitive task can be influenced by several aspects such as the level and duration of exertions. Among these aspects, though, the influence of cycle time remains unclear. Here, the effect of cycle time on LMF and performance was examined for a simple biomechanical system during repetitive static efforts. Participants performed 1-h trials of intermittent isometric index finger abduction with a duty cycle of 50% in all combinations of two cycle times (30 and 60s) and two exertion levels (15% and 25% of maximum voluntary capacity). Measures of discomfort, performance (force fluctuations), and muscle capacity (voluntary strength and low-frequency twitch responses) were obtained, all of which demonstrated a beneficial effect of the 30s cycle time. Specifically, the shorter cycle time led to lower rates of increase in perceived discomfort, lower rates of increase in force fluctuations, lower rates of decrease in voluntary capacity, and smaller changes in twitch responses. These benefits, reflecting less LMF development in the shorter cycle time, were quite consistent between genders and the two levels of effort. Results of this study can be used to modify current models predicting work-rest allowance and/or LMF, helping to enhance performance and reduce the risk of adverse musculoskeletal outcomes. PMID- 26995712 TI - Rare disease relations through common genes and protein interactions. AB - ODCs (Orphan Disease Connections), available at http://csbg.cnb.csic.es/odcs, is a novel resource to explore potential molecular relations between rare diseases. These molecular relations have been established through the integration of disease susceptibility genes and human protein-protein interactions. The database currently contains 54,941 relations between 3032 diseases. PMID- 26995709 TI - Bilateral symmetry in vision and influence of ocular surgical procedures on binocular vision: A topical review. AB - We analyze the role of bilateral symmetry in enhancing binocular visual ability in human eyes, and further explore how efficiently bilateral symmetry is preserved in different ocular surgical procedures. The inclusion criterion for this review was strict relevance to the clinical questions under research. Enantiomorphism has been reported in lower order aberrations, higher order aberrations and cone directionality. When contrast differs in the two eyes, binocular acuity is better than monocular acuity of the eye that receives higher contrast. Anisometropia has an uncommon occurrence in large populations. Anisometropia seen in infancy and childhood is transitory and of little consequence for the visual acuity. Binocular summation of contrast signals declines with age, independent of inter-ocular differences. The symmetric associations between the right and left eye could be explained by the symmetry in pupil offset and visual axis which is always nasal in both eyes. Binocular summation mitigates poor visual performance under low luminance conditions and strong inter-ocular disparity detrimentally affects binocular summation. Considerable symmetry of response exists in fellow eyes of patients undergoing myopic PRK and LASIK, however the method to determine whether or not symmetry is maintained consist of comparing individual terms in a variety of ad hoc ways both before and after the refractive surgery, ignoring the fact that retinal image quality for any individual is based on the sum of all terms. The analysis of bilateral symmetry should be related to the patients' binocular vision status. The role of aberrations in monocular and binocular vision needs further investigation. PMID- 26995713 TI - Morphological and molecular detection of canine dirofilarial species of veterinary and medical importance in Morogoro municipality, Tanzania. AB - A descriptive cross-sectional survey of Dirofilaria infections in dogs was carried out from January to March 2015 in Morogoro municipality, Tanzania. One hundred and fifty two blood samples were collected from healthy dogs aged more than 6 months living in different areas of Morogoro, and analyzed by modified Knott's technique for circulating microfilariae. Microfilaraemic samples were further analyzed by Polymerase chain reaction (PCR) and PCR products were sequenced for molecular identification. Microfilariae were detected by microscopy in 9 samples (5.92%), of which 6 tested positive by PCR. The 5.8S-internal transcribed spacer 2 (ITS2)-28S ribosomal DNA (rDNA) sequences generated were 97% identical to Dirofilaria immitis and 86% to 90% identical to D. repens, confirming the presence of D. immitis in Tanzania and showing the presence of D. repens, not previously observed. PMID- 26995714 TI - Injectable fipronil for cattle: Plasma disposition and efficacy against Rhipicephalus microplus. AB - Fipronil is a phenylpyrazole class insecticide. It is widely used as an insecticide in agriculture and in the control of ectoparasites in veterinary medicine. The application of fipronil in an injectable form (subcutaneously) becomes an innovation, since there is no commercially available preparation containing fipronil herein. The present study aimed at fipronil usage, applied subcutaneously in cattle, to control Rhipicephalus microplus. The assessing criteria used in the research have been the construction of the plasma concentration curve and efficacy studies. A method using High Performance Liquid Chromatograph with ultraviolet detection was developed for determination of fipronil in bovine plasma samples, providing a fast and simple process with good reproducibility and low limit of quantification. The validation of the analytical method showed linearity, selectivity, precision, accuracy, sensitivity and stability, thus proving it as suitable for routine analysis. This method showed to be an important investigative tool in the analysis of fipronil plasma concentration in cattle. Fipronil administered via subcutaneous in bovine reached the systemic circulation (Cmax=378.06+/-137.44 ng/mL), was quickly absorbed (t(max)=10+/-0.87 h), and its elimination occurred slowly (t(1/2)=12 days), while maintaining quantifiable blood plasma levels (23.79+/-12.16 ng/mL) for up to 21 days after the treatment with a 1 mg/kg dosage. The in vivo efficacy tests proved that fipronil applied subcutaneously in a single dose of 1 mg/kg in cattle exhibited a mean efficacy of 82.41% against R. microplus. The potential of subcutaneous injection as an alternative treatment route in cattle encourage the development of an injectable formulation of fipronil. PMID- 26995715 TI - Molecular identification of Sarcocystis spp. in foxes (Vulpes vulpes) and raccoon dogs (Nyctereutes procyonoides) from Germany. AB - More than 200 Sarcocystis spp. have been named and most of them appear to be involved in a particular predator-prey cycle. Among canids, the European fox (Vulpes vulpes) and the raccoon dog (Nyctereutes procyonoides) are widely distributed in Europe and probably play an important role as definitive hosts in the epidemiology of Sarcocystis spp. infections. A total of 50 small intestines from foxes and 38 from raccoon dogs were sampled in the Federal State of Brandenburg, Germany. Mucosal scrapings were collected and analyzed by sugar flotation and when oocysts or sporocysts were detected, an overnight sedimentation was performed and DNA extracted with a commercial kit. A PCR was conducted using primers targeting a fragment of the 18S rRNA gene (with a size of approximately 850 bp) and the amplicons were purified and sequenced. Samples with an inconclusive sequencing were cloned into plasmids and >= 3 plasmids from each amplicon were sequenced. Sarcocystis spp. oocysts/sporocysts were detected in 38% (19/50) of fox and 52.6% (20/38) of raccoon dog samples. Sequencing analysis of amplicons from oocyst DNA revealed mixed infections in 9 fox and 5 raccoon dog samples. In the fox samples, the most often identified Sarcocystis spp. were S. tenella or S. capracanis (10.0%); S. miescheriana (8.0%) and S. gracilis (8.0%) followed by Sarcocystis spp., which use birds as intermediate hosts (6.0%), and S. capreolicanis (4.0%). In the raccoon dog samples, sequences with a >=99% identity with the following species were detected: S. miescheriana (18.4%), S. gracilis (13.1%), Sarcocystis spp. using birds as IH (10.5%), S. tenella or S.capracanis (2.6%) and S. capreolicanis (2.6%). The estimated prevalence of Sarcocystis spp. infections determined using mucosal scrapings was higher than in related studies performed by analyzing faecal samples. The methodology of 18S rRNA gene amplification, cloning and sequencing is suitable to identify mixed infections with Sarcocystis spp. and to gather information on potential definitive hosts of these parasite species. PMID- 26995716 TI - Ribosomal DNA analysis of tsetse and non-tsetse transmitted Ethiopian Trypanosoma vivax strains in view of improved molecular diagnosis. AB - Animal trypanosomosis caused by Trypanosoma vivax (T. vivax) is a devastating disease causing serious economic losses. Most molecular diagnostics for T. vivax infection target the ribosomal DNA locus (rDNA) but are challenged by the heterogeneity among T. vivax strains. In this study, we investigated the rDNA heterogeneity of Ethiopian T. vivax strains in relation to their presence in tsetse-infested and tsetse-free areas and its effect on molecular diagnosis. We sequenced the rDNA loci of six Ethiopian (three from tsetse-infested and three from tsetse-free areas) and one Nigerian T. vivax strain. We analysed the obtained sequences in silico for primer-mismatches of some commonly used diagnostic PCR assays and for GC content. With these data, we selected some rDNA diagnostic PCR assays for evaluation of their diagnostic accuracy. Furthermore we constructed two phylogenetic networks based on sequences within the smaller subunit (SSU) of 18S and within the 5.8S and internal transcribed spacer 2 (ITS2) to assess the relatedness of Ethiopian T. vivax strains to strains from other African countries and from South America. In silico analysis of the rDNA sequence showed important mismatches of some published diagnostic PCR primers and high GC content of T. vivax rDNA. The evaluation of selected diagnostic PCR assays with specimens from cattle under natural T. vivax challenge showed that this high GC content interferes with the diagnostic accuracy of PCR, especially in cases of mixed infections with T. congolense. Adding betain to the PCR reaction mixture can enhance the amplification of T. vivax rDNA but decreases the sensitivity for T. congolense and Trypanozoon. The networks illustrated that Ethiopian T. vivax strains are considerably heterogeneous and two strains (one from tsetse-infested and one from tsetse-free area) are more related to the West African and South American strains than to the East African strains. The rDNA locus sequence of six Ethiopian T. vivax strains showed important differences and higher GC content compared to other animal trypanosomes but could not be related to their origin from tsetse-infested or tsetse-free area. The high GC content of T. vivax DNA renders accurate diagnosis of all pathogenic animal trypanosomes with one single PCR problematic. PMID- 26995717 TI - Bio-guided identification of proteins for the diagnosis of cysticercosis in swine. AB - Neurocysticercosis (NCC) is one of the most prevalent parasitic infection of the brain and the most common cause of seizures in adults in tropical countries. Cysticercosis is caused by larvae of Taenia solium, a human tapeworm. Pig or humans are infected by ingestion of eggs in food contaminated by human feces. Diagnosis and treatment of pigs is a pillar of the control of the disease in a country. However current diagnostic tests are based on ELISA and/or Western blot using native antigens needing laboratory facilities not available in rural areas. Development of a pen side diagnostic test for swines, makes sense. Immunochromatographic test should be adapted for this purpose. To design it we started a bio-guided identification of new proteins in cysticercus fluid. Proteins were analyzed using ion exchange chromatography and 2D separation and were selected by Western blot analysis using sera from infected/non infected pigs. Spots from the Coomassie-stained gel corresponding to these proteins were then analyzed by mass spectroscopy and proteins were identified using a bank of Expressed Sequence Tags (EST) of T. solium. Eighteen new proteins of interest were identified and nine were selected for further development. PMID- 26995718 TI - Molecular identification of Lutzomyia migonei (Diptera: Psychodidae) as a potential vector for Leishmania infantum (Kinetoplastida: Trypanosomatidae). AB - Visceral leishmaniasis (VL) in Brazil is caused by the protozoan Leishmania infantum. This parasite is transmitted by the bite of a female sand fly. The most important sand fly species in VL transmission is Lutzomyia longipalpis. In Fortaleza, the capital of Ceara State, Brazil, the simultaneous occurrence of Lutzomyia migonei and L. longipalpis was detected in localities where VL transmission is observed. The purpose of this study was to determine conclusively if L. migonei can be found naturally infected with L. infantum in key focus in Fortaleza. Using a CDC traps we performed phlebotomine capture during one year. External morphological features and qPCR targeting species-specific gene sequences of Lutzomyia species were used to identify the female phlebotomine sand flies. The molecular identification of the Leishmania species was performed using qPCR targeting species-specific gene sequences of L. infantum and Leishmania braziliensis. The males L. migonei abundance was higher in the rainy season. Humidity and rainfall positively correlated with males L. migonei abundance, while temperature showed a negative correlation. The correlation between the density of L. migonei female with rainfall, relative air humidity, and temperature were not statistically significant. According to the molecular data produced by qPCR amplifications, three positive sand flies were identified as L. longipalpis, and one was identified as L. migonei. The infection rate was 0.35% and 0.18%, respectively. The parasite load was 32,492+/-2572 L. infantum in L. migonei while the L. longipalpis had parasite loads between 2,444,964.6+/-116,000 and 6,287,130+/-124,277. Our findings confirm L. migonei as a potential vector of VL in Fortaleza at a molecular level. PMID- 26995719 TI - Vaccination against canine leishmaniosis increases the phagocytic activity, nitric oxide production and expression of cell activation/migration molecules in neutrophils and monocytes. AB - Visceral leishmaniasis (VL) is transmitted by phlebotomine sandfly vectors and domestic dogs serve as a reservoir. The elimination of seropositive dogs has been a recommended strategy for managing the disease in Brazil. A protective canine vaccine would be an important tool for controlling the disease, reducing the parasites available to sandfly vectors and, consequently, reducing the number of human VL cases. Leishmune((r)) is an anti-canine Leishmaniosis (VL Canine) vaccine produced by Zoetis (Pfizer, Brazil) that was commercially available in Brazil until 2014. The main goal of the present study was to investigate the protective immunological events induced by vaccination with Leishmune((r)) in the time frame of one year. Healthy, non-vaccinated dogs and dogs of 1, 6 and 10 months post-vaccination were evaluated. Results showed that Leishmune((r)) induced an increase in phagocytic activity of neutrophils and monocytes and also increased NO production. Immunological events were correlated with functional responses, as high levels of IgG and an increase of the receptor Fcgamma were detected. Vaccination induced an increased expression of TLR (2, 4, 5, 9), integrin (CD29, CD49f), activation (MHCII) and co-stimulatory (CD80, CD81) molecules by neutrophils and monocytes. Vaccination led to decrease of IL-4 and an increase of IL-8 production by monocytes and higher IFN-gamma and IL-17 production by T-cells. The results suggested that Leishmune((r)) was able to induce a long-lasting change in immune response, mediated by supportive immunological events that may be participating in protective immunity against CL. PMID- 26995720 TI - Molecular identification of Anisakis and Hysterothylacium larvae in commercial cephalopods from the Spanish Mediterranean coast. AB - This study aims to investigate the occurrence of nematode larvae in commercial cephalopods in the Western Mediterranean Sea. A total of 202 animals comprising 123 broadtail shortfin squid (Illex coindetii), 34 European squid (Loligo vulgaris) and 45 common octopus (Octopus vulgaris) were examined using enzymatic digestion. A total of 31 larvae were isolated (prevalence: 14.6%) and identified using molecular analyses which included PCR and sequencing of the ITS (ITS1-5.8S rDNA-ITS2) region. Phylogenetic tree inferred from ITS sequences yielded supported relationships for Anisakis (P: 12.2%) and Hysterothylacium species (P: 4.1%). All parasites were found parasitizing I. coindetii and, as expected, A. pegreffii presented the highest prevalence (11.4%). A. physeteris was also found with a lower prevalence (1.6%) but confirming the role of the broadtail shortfin squid as paratenic host and, its potential host for anisakidosis transmission. A hybrid larva between Anisakis simplex and A. pegreffi was also identified. All Anisakis larvae were found within the visceral cavity; in contrast most of the Hysterothylacium larvae were isolated from the mantle. A significant correlation was found between total nematode prevalence and depth, explained by the presence of larger broadtail shortfin squids inhabiting deeper depths. Therefore, the results obtained in the present study improve the knowledge of the occurrence of Anisakis and Hysterothylacium species in the I. coindetii from the Spanish Mediterranean Sea highlighting the importance of considering I. coindetii as a potential hazard for humans if it is consumed raw or not well cooked and the need of further research in other cephalopods. PMID- 26995721 TI - Comparison of three methods for the detection of Angiostrongylus vasorum in the final host. AB - Angiostrongylosis is potentially fatal parasitic nematode infection affecting dogs which can be difficult to diagnose. In recent years several microscopical, serological and molecular detection methods have been developed, however there are few studies that have compared the relative performance of these methods. Screening necropsy material from an opportunistic sample of 140 foxes (82 of which were considered to be infected with Angiostrongylus vasorum), indicated sensitivities of 84.1% for dissection and visual examination of plucks, 69.5% for nested PCR of an 18S rRNA fragment and 76.8% for a canine A. vasorum antigen detection test (IDEXX Angio Detect) of tissue fluid samples respectively. Agreement between the tests ranged from 45.6 to 79.7%. A novel nested PCR-RFLP for the detection and identification of canid lungworm spp. is described. PMID- 26995722 TI - Computer modelling of anthelmintic resistance and worm control outcomes for refugia-based nematode control strategies in Merino ewes in Western Australia. AB - This study utilised computer simulation modelling (Risk Management Model for Nematodes) to investigate the impact of different parasite refugia scenarios on the development of anthelmintic resistance and worm control effectiveness. The simulations were conducted for adult ewe flocks in a Mediterranean climatic region over a 20 year time period. Factors explored in the simulation exercise were environment (different weather conditions), drug efficacy, the percentage of the flock left untreated, the timing of anthelmintic treatments, the initial worm egg count, and the number of drenches per annum. The model was run with variable proportions of the flock untreated (0, 10, 20, 30, 40 and 50%), with ewes selected at random so that reductions in the mean worm burden or egg count were proportional to the treated section of the flock. Treatments to ewes were given either in summer (December; low refugia potential, hence highly selective) or autumn (March; less selective due to a greater refugia potential), and the use of different anthelmintics was simulated to indicate the difference between active ingredients of different efficacy. Each model scenario was run for two environments, specifically a lower rainfall area (more selective) and a higher rainfall area (less selective) within a Mediterranean climatic zone, characterised by hot, dry summers and cool, wet winters. Univariate general linear models with least square difference post-hoc tests were used to examine differences between means of factors. The results confirmed that leaving a proportion of sheep in a flock untreated was effective in delaying the development of anthelmintic resistance, with as low as 10% of a flock untreated sufficient to significantly delay resistance, although this strategy was associated with a small reduction in worm control. Administering anthelmintics in autumn rather than summer was also effective in delaying the development of anthelmintic resistance in the lower rainfall environment where all sheep were treated, although the effect of treatment timing on worm control effectiveness varied between the environments and the proportion of ewes left untreated. The use of anthelmintics with higher efficacy delayed the development of resistance, but the initial worm egg count or number of annual treatments had no effect on either the time to resistance development or worm control effectiveness. In conclusion, the modelling study suggests that leaving a small proportion of ewes untreated, or changing the time of treatment, can delay the onset of anthelmintic resistance in a highly selective environment. PMID- 26995723 TI - Severe seizures in pigs naturally infected with Taenia solium in Tanzania. AB - Neurocysticercosis (NCC) caused by Taenia solium is a serious neurological disease. In humans neurological symptoms have been thoroughly studied and documented, however, there is limited information on clinical signs in pigs infected with T. solium cysticerci. Among the scientific community, it is in fact believed that pigs with NCC rarely show neurological signs. The aim of this study was to describe clinical manifestations associated with NCC in pigs and correlate the manifestations to the number and distribution of cysticerci in brains of naturally infected pigs in Tanzania. Sixteen infected and 15 non-infected control pigs were observed for 14 days during daylight hours, and subsequently videotaped for another 14 consecutive days using close circuit television cameras. All occurrences of abnormal behaviour (trembling, twitching, mouth and ear paralysis, ataxia, dribbling, salivating, eye blinking, walking in circles) were recorded. At the end of the recording period, pigs were slaughtered and their brains dissected, cysticerci counted and locations noted. During the recording period, two infected pigs were observed having seizures. Some of the observed autonomic signs during a seizure were chewing motions with foamy salivation and ear stiffening. Motor signs included tonic muscle contractions followed by a sudden diminution in all muscle function leading to collapse of the animal. Stereotypic walking in circles was observed on several occasions. At dissection, both pigs had a high number of brain cysticerci (241 and 247 cysticerci). The two pigs with seizures were also older (36 months) compared to the others (18.3 months, +/- 8.2 standard deviation). Results of this study have shown that pigs with NCC can develop clinical signs and suffer from seizures like humans with symptomatic NCC. Results of this study could potentially open up a new experimental pathway to explore the aetiology of neurological symptoms in humans with NCC associated epilepsy. PMID- 26995724 TI - Population dynamics and evaluation of the partial selective treatment of crossbreed steers naturally infested with Rhipicephalus (Boophilus) microplus in a herd from the state of Minas Gerais in Brazil. AB - The present study aimed to evaluate the population dynamics of Rhipicephalus (Boophilus) microplus over a period of 13 months on a rural property located in the state of Minas Gerais in southeastern Brazil. Animals were treated for ticks indoors by whole body spraying when R. (B.) microplus had an average count equal or more than 30 ticks. The study also evaluated the possibility of a partial selective treatment for bovines to control R. (B.) microplus in which only a percentage of the population would be treated (specifically those bovines with tick counts of >=20. Moreover, we examined the percentage of the population of R. (B.) microplus present on experimental bovines that did not come into contact with the chemical compounds used in the partial selective treatment. We concluded that in this particular region of Brazil, the crossbreed steers support up to five R. (B.) microplus generations per year and that the number of generations was primarily affected by the pluviometric precipitation. We sprayed the bovines with chemicals seven times during the course of the study. The results of the partial selective treatment method revealed that during the rainy and the dry periods, 42.1% to 60.0% and 61.9% to 79.2% of the animals, respectively, fulfilled the criteria to receive a chemical treatment to reduce the number of cattle ticks. In consideration of the need to slow the development of tick resistance with the chemical compounds used in the spraying treatment, the results showed that the percentage of animals that did not require treatment is not relevant. This was evidenced by the result that bovines that presented tick counts of >=20 during the dry and rainy periods represented 91.5% and 90.6% of the total recorded R. (B.) microplus populations, respectively. Only 8.7% of the tick population remained free from exposure to acaricides during the 13 months of the study, which is an important point when considering the adoption of the partial selective treatment method. Future studies with larger herds must be conducted on these topics; however, our results suggest that the partial selective treatment method most likely will not slow the development of resistance in this R. (B.) microplus population against the chemical compound used in this study. PMID- 26995726 TI - Retrospective study on the distribution of Dirofilaria immitis in dogs in Hungary. AB - Europe has experienced the spreading of vector-borne helminths including heartworms (Dirofilaria immitis) from the Mediterranean countries towards the northern ones in the past decades. Recently, the establishment of D. immitis was confirmed in Hungary on the basis of period prevalence studies involving dogs, red foxes (Vulpes vulpes) and golden jackals (Canis aureus). The aim of our retrospective study was to describe the spatial distribution of the parasite and the time course of spreading of D. immitis in Hungary. Necropsy records of 2622 dogs received at our laboratories from 2001 to 2015 were reviewed for heartworm infections. The locality of origin of animals was recorded in a geographic information system database and compared to the results of the period prevalence study involving wild canids. Autochthonous heartworm infection was detected in 27 dogs. The time course analysis indicates that the parasite established in Hungary in 2007. As temperature is one of the most important determinants of the distribution of D. immitis, the climate of the Great Hungarian Plain is the most suitable region for the establishment of D. immitis in Hungary. Our studies revealed that the Great Hungarian Plain became a D. immitis endemic region for 2015. Nevertheless, sporadic cases in wild canids and dogs also occur in other regions of the country. PMID- 26995725 TI - Larval development assays reveal the presence of sub-populations showing high- and low-level resistance in a monepantel (Zolvix(r))-resistant isolate of Haemonchus contortus. AB - Resistance to the amino-acetonitrile derivative monepantel has been reported in several species of gastrointestinal nematodes over recent years. We were interested in the use of in vitro assays with free-living worm life-stages to detect resistance to this drug. We therefore used larval development and larval migration assays to examine dose response relationships for the drug against two susceptible and one resistant isolate of Haemonchus contortus. The resistant isolate was established by laboratory propagation of the survivors of a field treatment with Zolvix((r)) that had originally resulted in a drug efficacy of over 99%. Drug efficacy against this field-derived laboratory-propagated resistant isolate in vivo was approximately 15%. The larval development assay proved able to discriminate between the susceptible and resistant isolates, with larvae of the resistant isolate showing an ability to develop at higher drug concentrations than the two susceptible isolates. The resistant isolate showed the presence of two distinct subpopulations, separated by a plateau in the dose response curve. Sub-population 1 (approximately 40% of the total population) showed a low level of resistance with an IC50 increased approximately 7-fold compared to the baseline susceptible isolate, while sub-population 2 (the remaining 60% of the total population) showed an IC50 increased over 1000-fold compared to the baseline susceptible isolate. This level of resistance is unusually high for any gastrointestinal nematode species in drug dose-response in vitro assays. In contrast, the migration assay could not discriminate between the three isolates, with migration not reduced to zero at any of the drug concentrations tested. This study demonstrates that a larval development assay is able to detect resistance to monepantel in H. contortus, and that resistance can exist in two distinct forms. This suggests that at least two separate monepantel resistance mechanisms are acting within the worm isolate studied here, with one or more mechanisms conferring a much higher level of resistance than the other(s). PMID- 26995727 TI - Phenotypic assessment of the ovicidal activity of monepantel and monepantel sulfone on gastro-intestinal nematode eggs. AB - The in vitro ovicidal activity of the amino acetonitrile derivative, monepantel (MPTL) and its active metabolite monepantel sulfone (MPTL-SO2) were assessed against a number of commercially important nematode species of ruminants, namely Teladorsagia circumcincta, Haemonchus contortus and Trichostrongylus axei. An egg hatch test (EHT) was used to make the assessment of both drug sensitive and drug resistant isolates. Both MPTL and MPTL-SO2 showed moderate ovicidal activity in vitro against all of the species examined, although species specific differences as measured by inhibitory concentration were observed. Analysis of the drug sensitive isolates showed H. contortus to be the most sensitive to both MPTL and MPTL-SO2 (ED50 1.7 and 2.7 MUg/ml respectively) followed by T. circumcincta (ED50 2.1 and 2.7 MUg/ml respectively) followed by T. axei (ED50 68.7 and 60.1 MUg/ml respectively). Overall the EHT results would suggest no "global" in vitro discriminatory dose for detection of MPTL resistance is likely to be achievable, using the egg hatch test, due to large inherent variability observed between species. The test identified a dose dependent increase in MPTL and MPTL-SO2 sensitivity in two MPTL resistant T. circumcincta isolates and therefore offers to be a promising tool for the phenotypic characterisation of MPTL sensitivity, allowing exploration into the mechanisms involved in selection and development of MPTL resistance. PMID- 26995728 TI - The 'Toolbox' of strategies for managing Haemonchus contortus in goats: What's in and what's out. AB - A dynamic and innovative approach to managing the blood-consuming nematode Haemonchus contortus in goats is critical to crack dependence on veterinary anthelmintics. H. contortus management strategies have been the subject of intense research for decades, and must be selected to create a tailored, individualized program for goat farms. Through the selection and combination of strategies from the Toolbox, an effective management program for H. contortus can be designed according to the unique conditions of each particular farm. This Toolbox investigates strategies including vaccines, bioactive forages, pasture/grazing management, behavioural management, natural immunity, FAMACHA, Refugia and strategic drenching, mineral/vitamin supplementation, copper Oxide Wire Particles (COWPs), breeding and selection/selecting resistant and resilient individuals, biological control and anthelmintic drugs. Barbervax((r)), the ground-breaking Haemonchus vaccine developed and currently commercially available on a pilot scale for sheep, is prime for trialling in goats and would be an invaluable inclusion to this Toolbox. The specialised behaviours of goats, specifically their preferences to browse a variety of plants and accompanying physiological adaptations to the consumption of secondary compounds contained in browse, have long been unappreciated and thus overlooked as a valuable, sustainable strategy for Haemonchus management. These strategies are discussed in this review as to their value for inclusion into the 'Toolbox' currently, and the future implications of ongoing research for goat producers. Combining and manipulating strategies such as browsing behaviour, pasture management, bioactive forages and identifying and treating individual animals for haemonchosis, in addition to continuous evaluation of strategy effectiveness, is conducted using a model farm scenario. Selecting strategies from the Toolbox, with regard to their current availability, feasibility, economical cost and potential ease of implementation depending on the systems of production and their complementary nature, is the future of managing H. contortus in farmed goats internationally and maintaining the remaining efficacy of veterinary anthelmintics. PMID- 26995729 TI - Puberty marks major changes in the hippocampal and cortical c-Fos activation pattern induced by NMDA receptor antagonists. AB - Non-selective and subunit (GluN2B)-specific N-methyl-d-aspartate receptor (NMDAR) antagonists represent promising alternative antidepressant drugs with fast onset of the therapeutic action. The neuronal activation pattern induced by NMDAR antagonists is well characterized by c-Fos expression analysis only in the adult rodent brain. In contrast, there is little information available regarding their effects during postnatal development. Here we performed a systematic c-Fos brain mapping of the non-selective NMDAR antagonist MK-801 and the GluN2B-specific antagonist Ro 25-6981 from postnatal day 16 (P16) to P40. We found significant regional differences with gender-specificity in the activation pattern compared to the adult. Surprisingly, in the hippocampus, MK-801 triggered at pre-pubertal stages (especially at P24) very strong c-Fos expression, followed by low levels after P30, the approximate time point of puberty onset in mice. The cortical distribution of MK-801-triggered c-Fos expression before puberty differed also substantially from the adult brain, showing high levels only in deep cortical layers at pre-pubertal stages. In comparison, the cortical activation induced by Ro 25-6981 diminished from high pre-pubertal levels and was in comparison with that triggered by MK-801 low in the hippocampus. These results reveal highly dynamic changes in the c-Fos activation pattern induced by NMDAR antagonists during puberty. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. PMID- 26995730 TI - Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. AB - The kynurenine pathway (KP) of tryptophan metabolism has emerged in recent years as a key regulator of the production of both neuroprotective (e.g. kynurenic and picolinic acid, and the essential cofactor NAD+) and neurotoxic metabolites (e.g. quinolinic acid, 3-hydroxykynurenine). The balance between the production of the two types of metabolites is controlled by key rate-limiting enzymes such as indoleamine-2,3-dioxygenase (IDO-1), and in turn, molecular signals such as interferon-gamma (IFN-gamma), which activate the KP metabolism of tryptophan by this enzyme, as opposed to alternative pathways for serotonin and melatonin production. Dysregulated KP metabolism has been strongly associated with neurological diseases in recent years, and is the subject of increasing efforts to understand how the metabolites are causative of disease pathology. Concurrent with these endeavours are drug development initiatives to use inhibitors to block certain enzymes in the pathway, resulting in reduced levels of neurotoxic metabolites (e.g. quinolinic acid, an excitotoxin and N-Methyl-d-Aspartate (NMDA) receptor agonist), while in turn enhancing the bioavailability of the neuroprotective metabolites such as kynurenic acid. Neurodegenerative diseases often have a substantial autoimmune or inflammatory component; hence a greater understanding of how KP metabolites influence the inflammatory cascade is required. Additionally, challenges exist in diseases like multiple sclerosis (MS) and motor neurone disease (MND), which do not have reliable biomarkers. Clinical diagnosis can often be prolonged in order to exclude other diseases, and often diagnosis occurs at an advanced state of disease pathology, which does not allow a lengthy time for patient assessment and intervention therapies. This review considers the current evidence for involvement of the KP in several neurological diseases, in biomarkers of disease and also the parallels that exist in KP metabolism with what is known in other diseases such as HIV, Alzheimer's disease/dementia, infection, immune privilege and cardiovascular disease. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. PMID- 26995731 TI - Nitrate-Mediated Microbially Enhanced Oil Recovery (N-MEOR) from model upflow bioreactors. AB - Microbially Enhanced Oil Recovery (MEOR) can enhance oil production with less energy input and less costs than other technologies. The present study used different aqueous electron donors (acetate, glucose, molasses) and an aqueous electron acceptor (nitrate) to stimulate growth of heterotrophic nitrate reducing bacteria (hNRB) to improve production of oil. Initial flooding of columns containing heavy oil (viscosity of 3400cP at 20 degrees C) with CSBK (Coleville synthetic brine medium) produced 0.5 pore volume (PV) of oil. Bioreactors were then inoculated with hNRB with 5.8g/L of molasses and 0, 10, 20, 40, 60 or 80mM nitrate, as well as with 17mM glucose or 57mM acetate and 80mM nitrate. During incubations no oil was produced in the bioreactors that received 5.8g/L of molasses and 0, 10, 20, 40 or 60mM nitrate. However, the bioreactors injected with 5.8g/L of molasses, 17mM glucose or 57mM acetate and 80mM nitrate produced 13.9, 11.3+/-3.1 and 17.8+/-6.6% of residual oil, respectively. The significant production of oil from these bioreactors may be caused by N2-CO2 gas production. Following continued injection with CSBK without nitrate, subsequent elution of significant residual oil (5-30%) was observed. These results also indicate possible involvement of fermentation products (organic acids, alcohols) to enhance heavy oil recovery. PMID- 26995732 TI - Material grain size characterization method based on energy attenuation coefficient spectrum and support vector regression. AB - A grain size characterization method based on energy attenuation coefficient spectrum and support vector regression (SVR) is proposed. First, the spectra of the first and second back-wall echoes are cut into several frequency bands to calculate the energy attenuation coefficient spectrum. Second, the frequency band that is sensitive to grain size variation is determined. Finally, a statistical model between the energy attenuation coefficient in the sensitive frequency band and average grain size is established through SVR. Experimental verification is conducted on austenitic stainless steel. The average relative error of the predicted grain size is 5.65%, which is better than that of conventional methods. PMID- 26995733 TI - Analysis of two-phase sampling data with semiparametric additive hazards models. AB - Under the case-cohort design introduced by Prentice (Biometrica 73:1-11, 1986), the covariate histories are ascertained only for the subjects who experience the event of interest (i.e., the cases) during the follow-up period and for a relatively small random sample from the original cohort (i.e., the subcohort). The case-cohort design has been widely used in clinical and epidemiological studies to assess the effects of covariates on failure times. Most statistical methods developed for the case-cohort design use the proportional hazards model, and few methods allow for time-varying regression coefficients. In addition, most methods disregard data from subjects outside of the subcohort, which can result in inefficient inference. Addressing these issues, this paper proposes an estimation procedure for the semiparametric additive hazards model with case cohort/two-phase sampling data, allowing the covariates of interest to be missing for cases as well as for non-cases. A more flexible form of the additive model is considered that allows the effects of some covariates to be time varying while specifying the effects of others to be constant. An augmented inverse probability weighted estimation procedure is proposed. The proposed method allows utilizing the auxiliary information that correlates with the phase-two covariates to improve efficiency. The asymptotic properties of the proposed estimators are established. An extensive simulation study shows that the augmented inverse probability weighted estimation is more efficient than the widely adopted inverse probability weighted complete-case estimation method. The method is applied to analyze data from a preventive HIV vaccine efficacy trial. PMID- 26995734 TI - Partitioned log-rank tests for the overall homogeneity of hazard rate functions. AB - In survival analysis, it is routine to test equality of two survival curves, which is often conducted by using the log-rank test. Although it is optimal under the proportional hazards assumption, the log-rank test is known to have little power when the survival or hazard functions cross. To test the overall homogeneity of hazard rate functions, we propose a group of partitioned log-rank tests. By partitioning the time axis and taking the supremum of the sum of two partitioned log-rank statistics over different partitioning points, the proposed test gains enormous power for cases with crossing hazards. On the other hand, when the hazards are indeed proportional, our test still maintains high power close to that of the optimal log-rank test. Extensive simulation studies are conducted to compare the proposed test with existing methods, and three real data examples are used to illustrate the commonality of crossing hazards and the advantages of the partitioned log-rank tests. PMID- 26995736 TI - Surgical treatment of traumatic eventration with polyester button and polypropylene mesh to strengthen the suture technique in equine. AB - BACKGROUND: Defects in the abdominal wall of horses have high relapse rate. This is mainly in lateral eventrations and hernias caused by trauma from kicks of other horses or installation structures. The eventration region normally becomes swollen and there may be complications due to intestinal loop incarceration. The surgical treatment, consisting of reconstruction of the abdominal wall, frequently require biological or synthetic materials for the reinforcement of the suture line and tension support. Therefore, several studies have reported new materials for the repair of the abdominal wall, with the aim of improving the integration among adjacent tissues and reducing risks and complications such as rejection and infection. This report describes for the first time the use of a regular polypropylene mesh reinforced with polyester buttons for the herniorrhaphy. CASE PRESENTATION: A male, three-year-old, Appaloosa with 500 Kg presented to our hospital with a 10 days history of an increased volume on the left ventro-lateral region of the abdomen. During the physical examination, a deventration following traumatic rupture of the abdominal wall was diagnosed via ultrasonography. Then, the equine was anesthetized and moved to surgery for correction of the eventration which was performed according to conventional technique described in literature. Two days later, an eventration relapse was observed and confirmed via ultrasonography. After that, a second surgical intervention was performed using polyester buttons and polypropylene mesh. After the second surgical procedure, no complications related to eventration were observed either intra or postoperatively. After that, a recheck was performed thirty days later where satisfactory wound healing and total recovery were observed. CONCLUSION: The use of polypropylene mesh reinforced with polyester buttons is an effective technique for the repair of traumatic eventration in horses. This technique provides effective reinforcement against the abdominal tension and was a good option for reconstruction of lacerated muscles in cases of equine post-traumatic eventration, including relapsing cases. PMID- 26995739 TI - The morphogenesis of words ... it happens in science too! PMID- 26995738 TI - There's More Than Catastrophizing in Chronic Pain: Low Frustration Tolerance and Self-Downing Also Predict Mental Health in Chronic Pain Patients. AB - Among the potential range of irrational beliefs that could be used as predictors of physical and mental health, catastrophizing is the process that has received most attention in chronic pain research. Other irrational processes such as demandingness, low frustration tolerance, and self-downing have rarely been studied. The goal of this study was to explore whether this wider range of beliefs is associated with health in chronic pain patients beyond catastrophizing. A total of 492 chronic pain patients completed a measure of irrational beliefs, a measure of physical and mental health, and a numerical rating scale designed to assess pain intensity and interference. Irrational processes were more strongly associated with mental than with physical health. Low frustration tolerance and self-downing were found to be significantly related to mental health even after controlling for the effect of catastrophizing. Processes other than catastrophizing appear to have potentially important relationships with the mental health of people with chronic pain. These results may offer new intervention targets for practitioners. PMID- 26995737 TI - Perivascular adipose tissue: An unique fat compartment relevant for the cardiometabolic syndrome. AB - Type 2 diabetes and its major risk factor, obesity, are an increasing worldwide health problem. The exact mechanisms that link obesity with insulin resistance, type 2 diabetes, hypertension, cardiovascular complications and renal diseases, are still not clarified sufficiently. Adipose tissue in general is an active endocrine and paracrine organ that may influence the development of these disorders. Excessive body fat in general obesity may also cause quantitative and functional alterations of specific adipose tissue compartments. Beside visceral and subcutaneous fat depots which exert systemic effects by the release of adipokines, cytokines and hormones, there are also locally acting fat depots such as peri- and epicardial fat, perivascular fat, and renal sinus fat. Perivascular adipose tissue is in close contact with the adventitia of large, medium and small diameter arteries, possesses unique features differing from other fat depots and may act also independently of general obesity. An increasing number of studies are dealing with the "good" or "bad" characteristics and functions of normally sized and dramatically increased perivascular fat mass in lean or heavily obese individuals. This review describes the origin of perivascular adipose tissue, its different locations, the dual role of a physiological and unphysiological fat mass and its impact on diabetes, cardiovascular and renal diseases. Clinical studies, new imaging methods, as well as basic research in cell culture experiments in the last decade helped to elucidate the various aspects of the unique fat compartment. PMID- 26995740 TI - MCL1 is a key regulator of steroidogenesis in mouse Leydig cells. AB - Myeloid cell leukemia-1 (MCL1), an anti-apoptotic member of the BCL2 family, is expressed abundantly in the testis. Previous characterization revealed that MCL1 is expressed exclusively in the Leydig cells in the mouse testis, yet what it does in these cells remains unknown. We therefore analyzed testosterone biosynthesis in isolated primary Leydig cells and the MA-10 cell line, in which MCL1 was knocked down using an siRNA strategy. The mRNA abundance of the steroidogenic genes Star, Cyp11a1, Cyp17a1, Hsd3b1, Srd5a, and the luteinizing hormone/choriogonadotropin receptor Lhcgr were significantly reduced following MCL1 knockdown. Of the two enzymes required for testosterone biosynthesis, STAR and P450 SCC (encoded by Cyp11a1) enzyme abundance was also reduced following Mcl1 siRNA treatment, possibly leading to the reduced production of sex steroid precursors, and testosterone in these knockdown cells. Despite its classification as an anti-apoptosis protein, Mcl1 siRNA treatment did not affect cell survival. Collectively, our findings indicate that MCL1 plays a pivotal role in Leydig-cell steroidogenesis, and might provide novel insights into metabolic regulation in this cell. Mol. Reprod. Dev. 83: 226-235, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26995741 TI - Genetic Evidence of a Population Bottleneck and Inbreeding in the Endangered New Zealand Sea Lion, Phocarctos hookeri. AB - The New Zealand sea lion (NZSL) is of high conservation concern due to its limited distribution and its declining population size. Historically, it occupied most of coastal New Zealand, but is now restricted to a few coastal sites in southern mainland New Zealand and the sub-Antarctic Islands. NZSLs have experienced a recent reduction in population size due to sealing in the 1900s, which is expected to have resulted in increased inbreeding and a loss of genetic variation, potentially reducing the evolutionary capacity of the species and negatively impacting on its long-term prospects for survival. We used 17 microsatellite loci, previously shown to have cross-species applications in pinnipeds, to determine locus- and population-specific statistics for 1205 NZSLs from 7 consecutive breeding seasons. We show that the NZSL population has a moderate level of genetic diversity in comparison to other pinnipeds. We provide genetic evidence for a population reduction, likely caused by historical sealing, and a measure of allele sharing/parental relatedness (internal relatedness) that is suggestive of increased inbreeding in pups that died during recent epizootic episodes. We hypothesize that population bottlenecks and nonrandom mating have impacted on the population genetic architecture of NZSLs, affecting its population recovery. PMID- 26995742 TI - Candidate Gene Analysis Suggests Untapped Genetic Complexity in Melanin-Based Pigmentation in Birds. AB - Studies on melanin-based color variation in a context of natural selection have provided a wealth of information on the link between phenotypic and genetic variation. Here, we evaluated associations between melanic plumage patterns and genetic polymorphism in the Reunion grey white-eye (Zosterops borbonicus), a species in which mutations on MC1R do not seem to play any role in explaining melanic variation. This species exhibits 5 plumage color variants that can be grouped into 3 color forms which occupy discrete geographic regions in the lowlands of Reunion, and a fourth high-elevation form which comprises 2 color morphs (grey and brown) and represents a true color polymorphism. We conducted a comprehensive survey of sequence variation in 96 individuals at a series of 7 candidate genes other than MC1R that have been previously shown to influence melanin-based color patterns in vertebrates, including genes that have rarely been studied in a wild bird species before: POMC, Agouti, TYR, TYRP1, DCT, Corin, and SLC24A5 Of these 7 genes, 2 (Corin and TYRP1) displayed an interesting shift in allele frequencies between lowland and highland forms and a departure from mutation-drift equilibrium consistent with balancing selection in the polymorphic highland form only. Sequence variation at Agouti, a gene frequently involved in melanin-based pigmentation patterning, was not associated with color forms or morphs. Thus, we suggest that functionally important changes in loci other than those classically studied are involved in the color polymorphism exhibited by the Reunion grey white-eye and possibly many other nonmodel species. PMID- 26995744 TI - Operative management of high-grade dysplastic L5 spondylolisthesis with the use of external transpedicular fixation: advantages and drawbacks. AB - PURPOSE: The aim of our study was to analyze clinical and radiographic outcomes of operative management of L5 high-grade dysplastic spondylolisthesis with the apparatus for external transpedicular fixation (AETF), and to compare the results of its use for reduction and spondylodesis. METHODS: There were 13 patients with L5 dysplastic spondylolisthesis of grade 4 (Meyerding grading) and having a mean age of 25.0 +/- 3.6 years. The management included two stages: gradual reduction with the AETF, followed by either isolated anterior spondylodesis with the same AETF (group 1, n = 8), or by spondylodesis using a combined method (internal transpedicular instrumentation and posterior lumbar interbody fusion [PLIF]) (group 2, n = 5). Clinical evaluation included pain (VAS scale) and functional status (Oswestry questionnaire [ODI]). Reduction and fusion completeness were assessed radiographically after treatment and at a mean follow-up of 2.1 +/- 0.4 years. RESULTS: Initial slippage was reduced by 51.6 % with AETF and was of grade 1 or 2. Reduction made up 31.1 % at follow-ups (grade 2 or 3). Pain decreased by 57.6 % (p < 0.01). The functional status improved. ODI decreased by 37.7 % (p < 0.01) after treatment and by 41.7 % (p < 0.01) at follow-ups. Fusion at the level of the involved segment was poor in group 1. All the cases fused in group 2. CONCLUSIONS: The use of AETF for L5 high-grade dysplastic spondylolisthesis provides gradual controlled reduction of the slipped vertebra, decompression of cauda equine roots, and recovery of the local sagittal spinal column balance. It creates conditions for achieving stability of lumbosacral segments with combined spondylodesis (internal transpedicular instrumentation and PLIF). AETF is not suitable for spondylodesis due to a high rate of pseudarthrosis. PMID- 26995743 TI - Effects of hypoxia and reoxygenation on the antioxidant defense system of the locomotor muscle of the crab Neohelice granulata (Decapoda, Varunidae). AB - Crustaceans often occur in areas with variations in oxygen and experience situations known as hypoxia and reoxygenation. Consequences of such situations are increased levels of reactive oxygen species. To avoid oxidative damage intertidal crabs appear to possess an efficient antioxidant defense system (ADS). However, to date, studies have not addressed the strategies that are adopted by the crabs when exposed to hypoxia/reoxygenation cycles. Towards this end we evaluated the ADS and the role of melatonin as an antioxidant in the locomotor muscle of the crab Neohelice granulata under conditions of severe hypoxia and reoxygenation. Total antioxidant capacity against peroxyl radicals and the enzymes superoxide dismutase, catalase, glutathione peroxidase (GPx), and glutathione-S-transferase as well as the key enzyme of glutathione synthesis, glutamate cysteine ligase (GCL), were evaluated. Furthermore, GSH, GSH/GSSG index as well as hemolymph and cellular melatonin levels were evaluated. During hypoxia, increased GPx and GCL activity and decreased GSH and mitochondrial melatonin levels were observed, but during reoxygenation catalase activity increased and cytosolic melatonin levels decreased. It appears that the ADS in the locomotor muscle of N. granulata exert a modulating effect when being confronted with hypoxia and reoxygenation to avoid oxidative stress. During hypoxia, the ADS appear to target GPX activity as well as GSH and mitochondrial melatonin. During reoxygenation, however, evidence suggests that catalase and cytosolic melatonin are involved in the recovery of the locomotor muscle from oxidative damage and the suppression of further damage. PMID- 26995746 TI - [Two-year experience with cell salvage in total hip arthroplasty]. AB - BACKGROUND AND OBJECTIVE: The aim of this study was to determine the efficacy of the cell salvage system in total hip arthroplasty surgeries and whether the cell salvage system can reduce the allogeneic blood transfusion requirement in total hip arthroplasty patients. METHODS: We reviewed retrospectively the medical records of patients who underwent hip arthroplasty surgeries between 2010 and 2012 in a university hospital. A total of 181 arthroplasty patients were enrolled in our study. RESULTS: In the cell salvage group, the mean perioperative rate of allogeneic blood transfusion was significantly lower (92.53+/-111.88mL) than that in the control group (170.14+/-116.79mL; p<0.001). When the mean postoperative transfusion rates were compared, the cell salvage group had lower values (125.37+/-193.33mL) than the control group (152.22+/-208.37mL), although the difference was not statistically significant. The number of patients receiving allogeneic blood transfusion in the CS group (n=29; 43.2%) was also significantly lower than control group (n=56; 73.6%; p<0.05). In the logistic regression analysis, perioperative amount of transfusion, odds ratio (OR) -4.257 (95% CI 0.502 to 0.184) and operation time, OR: 2.720 (95% CI 0.001-0.004) were independent risk factors for the usage of cell salvage system. CONCLUSION: Cell salvage is an effective strategy for reducing the need for allogeneic blood transfusion in the perioperative setting; it provides support to patient blood management interventions. Thus, we recommend the cell salvage system for use in total hip arthroplasty surgeries to reduce the need for allogeneic blood transfusion, if possible. PMID- 26995745 TI - Emerging Therapies in Antiphospholipid Syndrome. AB - Antiphospholipid syndrome (APS) is a hypercoagulable state characterized by arterial and venous thromboses and pregnancy morbidity in the presence of antiphospholipid antibodies. Although warfarin remains the main therapeutic choice in APS, there is still concern about its efficacy, safety, and patient compliance. Patients with refractory APS to conventional therapy as well as patients with non-classical manifestations of APS may have alternative treatment approaches. APS pathogenesis has been further elucidated over the past years identifying new molecules as potential new treatment targets. This review summarizes available data from in vitro and animal models and clinical studies on the role of new potential treatment approaches including new oral anticoagulants and immunoregulatory agents: direct thrombin or factor Xa inhibitors, hydroxychloroquine, statins, B cell inhibition, complement inhibition, peptide therapy, nuclear factor kappaB and p38 mitogen-activated kinase inhibitors, defibrotide, abciximab, mTOR inhibitor, and other potential targets. Large multicenter prospective studies of well-characterized APS patients are needed to assess the efficacy and safety profile of these potential treatment alternatives. PMID- 26995747 TI - Neural correlates of 12-h abstinence-induced craving in young adult smokers: a resting-state study. AB - Studying the neural correlates of craving to smoke in young adulthood is of great importance to improve treatment outcomes in nicotine dependence. Previous nicotine dependence studies mainly focused on the neural substrates of craving elicited by smoking-related cues. More explicit attention to abstinence-induced craving during resting state in nicotine dependence has the potential to yield valuable information about craving, and characterizing this kind of craving is critical for developing effective interventions. Twenty-five young male smokers were enrolled in the present study. A within-subject experiment design was carried out to compare regional homogeneity (ReHo) between 12-h smoking abstinence and smoking satiety conditions during resting state in young adult smokers. Then, the ReHo changes associated with smoking abstinence (compared with satiety) were further examined for correlations with abstinence-induced changes in subjective craving. We found young adult smokers in abstinence state (compared with satiety) had higher ReHo in brain regions in fronto-striatal circuits including bilateral caudate, anterior cingulate cortex (ACC) and bilateral dorsal lateral prefrontal cortex (DLPFC), as well as brain regions in default mode network (DMN) including posterior cingulate cortex (PCC)/precuneus and angular gyrus. Additionally, we found the ReHo changes of the ACC and the bilateral caudate were positively correlated with the changes in craving induced by abstinence (i.e., abstinence minus satiety) in young adult smokers. The present findings improve the understanding of the effects of acute smoking abstinence on spontaneous brain activity and may contribute new insights into the neural mechanism of abstinence-induced craving in nicotine dependence. PMID- 26995750 TI - Are you a budding academic writer? AB - Academic writing can seem a daunting prospect although with the right support and information it can be more achievable than you think. In this first set of editorial comments of 2016, editors from all sections of the Health Information and Libraries Journal outline the origins of the individual section of the journal which they oversee and highlight some of the things you might want to consider when thinking of submitting your writing for publication. PMID- 26995751 TI - Can Twitter improve your health? An analysis of alcohol consumption guidelines on Twitter. AB - This article is the first in the feature to highlight the social network site Twitter as a tool for health information and it reports on a study by Emma Hughes, who completed an MSc in information and library studies at Aberystwyth University in 2014. Emma's research investigated the quality of health information available on Twitter, in particular the information available on UK alcohol consumption guidelines. Her research suggests that users searching for this information would need certain literacy skills to interpret it correctly. However, there is no doubt that Twitter is an increasingly popular resource for information dissemination and health professionals, and organisations should be encouraged to use it frequently as a tool for sharing information. AM. PMID- 26995752 TI - Global publication trends in the Health Information and Libraries Journal, 2014 2015. AB - In an age when health science librarians are encouraged to engage in research, it is worth considering how international the published literature is. This article analyses the authorship of articles in Health Information & Libraries Journal over a 1-year period, to determine the country of the authors who were published. JM. PMID- 26995749 TI - beta1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats. AB - Bisoprolol, an antagonist of beta1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts. PMID- 26995753 TI - Online learning: the brave new world of massive open online courses and the role of the health librarian. AB - In a wired, virtual and information rich society, MOOCs (Massive Open Online Courses) are leading us into a brave new world in which their key role is to support lifelong networked learning. This feature looks at the broad role of MOOCs and considers them within the context of health, and health librarianship. In particular, it provides examples of where health librarians have developed MOOCs and what opportunities there are in the future for health librarians to collaborate in the development and delivery of health MOOCs. H.S. PMID- 26995754 TI - [Medical homes and poles including pharmacists: An inventory]. AB - INTRODUCTION: The current restructuring of primary healthcare aims toward the creation of coordinated practices, which involves new roles for pharmacists. The objectives of this study were to identify all the French multidisciplinary medical homes and poles (MMHs and MMPs) with pharmacists currently active, and to describe how they are organized and operate. METHODS: This study focused on metropolitan MMHs and MMPs, active during the second semester of 2013, which include one or several pharmacists. These centers were identified through information provided by French regional health authorities (Agences regionales de sante, ARS) and the French medical homes medical poles federation (Federation francaise des maisons et poles de sante). Data were collected via an electronic questionnaire. RESULTS: Pharmacists were active in 60 centers in total, namely 35 MMHs and 25 MMPs. These were mostly set up as societes interprofessionnelles de soins ambulatoires (SISA, a type of company), with the help of government funding, typically from the ARS, in buildings owned by local government agencies. Pharmacists were systematically invited to attend interprofessional meetings held in the MMHs and MMPs, and multimodal treatment protocols were often in place. Pharmacists had no access to shared clerical services in MMHs, and rarely in MMPs, and their access to medical records was inconsistent in the two types of structures. CONCLUSION: Pharmacists are currently active in nearly one in four MMHs and MMPs but are still only partially integrated therein. PMID- 26995756 TI - Hypoglycaemia: costs, insulins and prevention. PMID- 26995757 TI - Driving and insulin-treated diabetes: are we aware of changes in the Third European Driving Licence Directive? PMID- 26995755 TI - Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis. AB - Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs have been reported to be involved in development of bone lesions in MM. However, the circulating microRNA as diagnostic and prognostic biomarkers for bone lesions has not been elucidated yet. In this study, we identified differentially expressed miRNAs that are potentially involved in myeloma-related bone disease in serum of MM patients. MiR-214 and miR-135b was shown to be increased in serum of MM patients with bone lesions. Serum level of miR-214 and miR-135b was highly correlated with the severity of lytic bone lesions and demonstrated as a diagnostic tool for identifying bone diseases based on results of a receiver operating characteristic analysis (ROC). In addition, patients with high levels of serum miR-214 had a dismal survival with significantly shortened progression free survival (PFS) and overall survival (OS). Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Taken together, our findings revealed the significance of circulating miR-214 and miR-135b levels in detection of bone disease and in prediction of prognosis of patients with multiple myeloma, suggesting its potential clinical applications. The result of this study also set the foundation for searching more circulating miRNA as biomarker for tumor bone lesions. PMID- 26995758 TI - Elucidation of the physicochemical properties and potency of siRNA-loaded small sized lipid nanoparticles for siRNA delivery. AB - Because nanoparticles with diameters less than 50nm penetrate stromal-rich tumor tissues more efficiently, the synthesis of small-sized nanoparticles encapsulating short interfering RNA (siRNA) is important in terms of realizing novel siRNA medicine for the treatment of various cancers. Lipid nanoparticles (LNPs) are the leading systems for the delivery of siRNA in vivo. Limit size LNPs were successfully synthesized using a microfluidic mixing technique. However, the physicochemical properties and potential for in vivo siRNA delivery of the limit size LNPs have not been examined in detail. In the present study, we prepared LNPs with different diameters from 32 to 67nm using a microfluidic mixing devise and examined the physicochemical properties of the particles and the potential for their use in delivering siRNA in vitro and in vivo to liver. Reducing the size of the LNPs causes poor-packing and an increased surface area, which result in their instability in serum. Moreover, it was revealed that the ability of endosomal escape (cytosolic siRNA release) of the smaller LNPs is subject to inhibition by serum compared to that of larger counterparts. Taken together, an increase in packing and avoiding the adsorption of serum components are key strategies for the development of next-generation highly potent and small-sized LNPs. PMID- 26995759 TI - How successful is nuclear targeting by nanocarriers? AB - The nucleus is ultimately the final target for many therapeutics treating various disorders including cancers, heart dysfunction and brain disorders. Owing to their specialized cell uptake and trafficking mechanisms, nanoparticles (NPs) allow drug targeting where degradation sensitive therapeutics could be delivered to their target tissues and cell in active form and sufficient concentration. However, it has recently become increasingly obvious that cytosolic internalization of a drug molecule does not entail its interaction with its subcellular target and hence careful nanoparticle design and optimization is required to enable nuclear targeting. This review, discusses the barriers to NP nuclear delivery; crossing the cell membrane, endo/lysosomal escape, cytoplasmic trafficking and finally nuclear entry focusing on how NP synthesis and modification could allow for bypassing each of the aforementioned barriers and successfully reaching the nucleus. Examples of nuclear targeted NPs are also discussed, stressing on the critical aspects of nuclear targeting and pointing out how the disease state might change the normal NP path and how such change could be exploited to increase efficiency of nuclear targeting. Finally, the criteria set for the evaluation of nanocarriers for nuclear delivery are discussed highlighting that quantitative rather than qualitative evaluation is required to evaluate how successful nanocarriers for nuclear delivery are, particularly with regards to the amount of drug delivered and released in the nucleus. PMID- 26995760 TI - A novel method for imaging sites of paracellular passage of macromolecules in epithelial sheets. AB - Understanding the dynamics of intestinal barrier function is key to elucidating oral delivery routes of therapeutics as well as to understanding various diseases that involve the mucosal immune system. Passage of macromolecules across barrier forming epithelia is classically analyzed by means of various tracer flux measurements. This approach averages over contributions from many cells and lacks labeling of passage-sites. Thus, abundance and nature of involved cells have remained unidentified. We present a novel method that allowed for optical analysis of passage of various macromolecules on large-scale and single-cell level. To achieve tracking of passage loci in epithelia at submicrometer resolution we used biotinylated and fluorescent macromolecules that bind to basolateral membranes pre-labeled with cell-adherent avidin. We applied this method to epithelial cell lines and isolated mucosae in order to 3-dimensionally determine barrier leak properties over time. Tracer passage was found in all epithelia examined. However, it was infrequent, strikingly inhomogeneous, depended on culture duration and tightness of the monolayer. Stimulating passage with barrier-perturbing agents increased the number of leaks exposition time dependently in cell lines and explanted mucosae. After stepwise opening of the paracellular passage pathway, integrated tracer-signal measured by our assay strictly correlated to simultaneously performed standard fluxes. Thus, our assay allows for the study of transepithelial macromolecule passage in various physiological and pathological conditions. PMID- 26995761 TI - Effects of a block in cysteine catabolism on energy balance and fat metabolism in mice. AB - To gain further insights into the effects of elevated cysteine levels on energy metabolism and the possible mechanisms underlying these effects, we conducted studies in cysteine dioxygenase (Cdo1)-null mice. Cysteine dioxygenase (CDO) catalyzes the first step of the major pathway for cysteine catabolism. When CDO is absent, tissue and plasma cysteine levels are elevated, resulting in enhanced flux of cysteine through desulfhydration reactions. When Cdo1-null mice were fed a high-fat diet, they gained more weight than their wild-type controls, regardless of whether the diet was supplemented with taurine. Cdo1-null mice had markedly lower leptin levels, higher feed intakes, and markedly higher abundance of hepatic stearoyl-CoA desaturase 1 (SCD1) compared to wild-type control mice, and these differences were not affected by the fat or taurine content of the diet. Thus, reported associations of elevated cysteine levels with greater weight gain and with elevated hepatic Scd1 expression are also seen in the Cdo1-null mouse model. Hepatic accumulation of acylcarnitines suggests impaired mitochondrial beta-oxidation of fatty acids in Cdo1-null mice. The strong associations of elevated cysteine levels with excess H2 S production and impairments in energy metabolism suggest that H2 S signaling could be involved. PMID- 26995762 TI - From yeast to human: exploring the comparative biology of methionine restriction in extending eukaryotic life span. AB - Methionine restriction is a widely reported intervention for increasing life span in several model organisms. Low circulating levels of methionine are evident in the long-lived naked mole-rat, suggesting that it naturally presents with a life extending phenotype akin to that observed in methionine-restricted animals. Similarly, long-lived dwarf mice also appear to have altered methionine metabolism. The mechanisms underlying methionine-restriction effects on life-span extension, however, remain unknown, as do their potential connections with caloric restriction, another well-established intervention for prolonging life span. Paradoxically, methionine is enriched in proteins expressed in mitochondria and may itself serve an important role in the detoxification of reactive oxygen species and may thereby contribute to delayed aging. Collectively, we highlight the evidence that modulation of the methionine metabolic network can extend life span-from yeast to humans-and explore the evidence that sulfur amino acids and the concomitant transsulfuration pathway play a privileged role in this regard. However, systematic studies in single organisms (particularly those that exhibit extreme longevity) are still required to distinguish the fundamental principles concerning the role of methionine and other amino acids in regulating life span. PMID- 26995764 TI - Corrigendum for Ann. N. Y. Acad. Sci. 1362: 200-214. PMID- 26995765 TI - Corrigendum for Ann. N. Y. Acad. Sci. 1337: 53-61. PMID- 26995766 TI - Tetramethoxy-Aminorhodamine (TMARh): A Bichromophore, an Improved Fluorophore, and a pH Switch. AB - Rhodamine is one of the most widely used fluorescent dyes. Here, a new synthetic pathway to the popular dyes is reported and the effect of adding four methoxy groups to the molecular structure is investigated. Tetramethoxy-aminorhodamine (TMARh) is found to show superior pH switching compared to the rhodamine without the four methoxy groups, owing to changed properties of the dark "off" state and increased fluorescence intensity in the protonated "on" state. PMID- 26995767 TI - Lipopolysaccharide and beta-1, 3-glucan binding protein (LGBP) stimulates prophenoloxidase activating system in Chinese mitten crab (Eriocheir sinensis). AB - Melanization mediated by prophenoloxidase (proPO) activating system play an essential role in killing invading microorganisms in invertebrates. Lipopolysaccharide and beta-1, 3-glucan binding protein (LGBP) as a pattern recognition protein have been demonstrated to active the proPO cascade in insect and shrimp. In this study, we investigated the role of LGBP in prophenoloxidase cascade-induced melanization in Chinese mitten crab (Eriocheir sinensis). By RT PCR analysis, EsLGBP was detected in all tested tissues, and showed highest expression in hemocytes, gill, intestine and brain. The expression of EsLGBP was up-regulated in the hemocytes following injections of LPS and beta-1, 3-glucan. The recombinant EsLGBP protein (rEsLGBP) was produced via prokaryotic expression system and affinity chromatography. By western blotting, rEsLGBP was discovered to exhibit the ability to bind to all tested microorganisms, including Gram negative bacteria, Gram-positive bacteria and yeast (Pichia pastoris). Meanwhile we found rEsLGBP has a high binding activity towards microbial immune elicitors such as LPS and beta-1, 3-glucan whereas no binding activity is detected with peptidoglycan. Moreover, the effects of RNAi-mediated blockade of EsLGBP were investigated on bacterial counts in the hemolymph and cumulative mortality rate of crabs infected with Vibrio parahaemolyticus in vivo. Further experiments demonstrate that rEsLGBP can trigger the whole hemolymph dependent melanization and stimulate to proPO cascade in vitro. Taken together, these results provide experimental evidence for role of LGBP in innate immunity, especially in the activation of prophenoloxidase activating system. PMID- 26995769 TI - Transcriptomic responses in the fish intestine. AB - The intestine, being a multifunctional organ central to both nutrient uptake, pathogen recognition and regulating the intestinal microbiome, has been subjected to intense research. This review will focus on the recent studies carried out using high-throughput gene expression approaches, such as microarray and RNA sequencing (RNA-seq). These techniques have advanced greatly in recent years, mainly as a result of the massive changes in sequencing methodologies. At the time of writing, there is a transition between relatively well characterised microarray platforms and the developing RNA-seq, with the prediction that within a few years as costs decrease and computation power increase, RNA-seq related approaches will supersede the microarrays. Comparisons between the approaches are made and specific examples of how the techniques have been used to examine intestinal responses to pathogens, dietary manipulations and osmoregulatory challenges are given. PMID- 26995771 TI - Telling the patients about diagnosis and outcome of schizophrenia: what, when and how? PMID- 26995770 TI - Extended pelvic lymphadenectomy in patients with clinically localised prostate cancer: A prospective observational study. AB - OBJECTIVE: To determine the frequency of lymph node involvement in patients with clinically localised prostate adenocarcinoma who had radical prostatectomy and extended pelvic lymphadenectomy. MATERIAL AND METHODS: A prospective observational study was conducted on 137 patients with clinically localised prostate cancer of low, intermediate or high risk according to the D'Amico classification. All participants underwent radical prostatectomy plus extended pelvic lymphadenectomy in 3 reference centres in Bogota, Colombia, between 2013 and 2014. The following variables were assessed: age, prostate specific antigen levels, Gleason score of the biopsy, probability of lymph node involvement calculated with Partin tables and the histopathology result of the surgical specimen, with the definitive Gleason pattern and the total number of resected and involved lymph nodes per tumour, according to the territory of the dissection. RESULTS: A total of 2,876 lymph nodes were extracted (an average of 20.99 lymph nodes per patient). There was lymph node involvement in 14 (10.22%) patients. The high-risk and intermediate-risk group presented lymph node metastases in 28.57% and 5.25%, respectively. There was no lymph node involvement in the low-risk group. Of the patients at risk of lymph node involvement (>=2% according to the Partin tables), 19.40% had lymph node metastases. CONCLUSION: Lymph node involvement in our population is similar to that reported in the worldwide literature. Extended pelvic lymphadenectomy increased the probability of detecting lymph node metastases in our community. PMID- 26995772 TI - Oxidative stress and the evolutionary origins of preeclampsia. AB - In this speculative paper, I consider the relationship between oxidative stress and the evolution of placentation in eutherian mammals. I argue that epitheliochorial placentation, in which fetal tissues remain separated from maternal blood throughout gestation, has evolved as a protective mechanism against oxidative stress arising from pregnancy, particularly in species with unusually long gestation periods and unusually large placentas. Human beings comprise an unusual species that has the life history characteristics of an epitheliochorial species, but exhibits hemochorial placentation, in which fetal tissues come into direct contact with maternal blood. I argue that the risk of preeclampsia has arisen as a consequence of the failure of human beings to evolve epitheliochorial placentation. PMID- 26995773 TI - Emulsion characteristics, chemical and textural properties of meat systems produced with double emulsions as beef fat replacers. AB - In recent years, double emulsions are stated to have a promising potential in low fat food production, however, there are very few studies on their possible applications in meat matrices. We aimed to investigate the quality of beef emulsion systems in which beef fat was totally replaced by double emulsions (W1/O/W2) prepared with olive oil and sodium caseinate (SC) by two-step emulsification procedure. Incorporation of W1/O/W2 emulsion resulted in reduced lipid, increased protein content, and modified fatty acid composition. W1/O/W2 emulsion treatments had lower jelly and fat separation, higher water-holding capacity and higher emulsion stability than control samples with beef fat. Increased concentrations of W1/O/W2 emulsions resulted in significant changes in texture parameters. TBA values were lower in W1/O/W2 emulsion treatments than control treatment after 60days of storage. In conclusion, our study confirms that double emulsions had promising impacts on modifying fatty acid composition and developing both technologically and oxidatively stable beef emulsion systems. PMID- 26995768 TI - B cells and their role in the teleost gut. AB - Mucosal surfaces are the main route of entry for pathogens in all living organisms. In the case of teleost fish, mucosal surfaces cover the vast majority of the animal. As these surfaces are in constant contact with the environment, fish are perpetually exposed to a vast number of pathogens. Despite the potential prevalence and variety of pathogens, mucosal surfaces are primarily populated by commensal non-pathogenic bacteria. Indeed, a fine balance between these two populations of microorganisms is crucial for animal survival. This equilibrium, controlled by the mucosal immune system, maintains homeostasis at mucosal tissues. Teleost fish possess a diffuse mucosa-associated immune system in the intestine, with B cells being one of the main responders. Immunoglobulins produced by these lymphocytes are a critical line of defense against pathogens and also prevent the entrance of commensal bacteria into the epithelium. In this review we will summarize recent literature regarding the role of B-lymphocytes and immunoglobulins in gut immunity in teleost fish, with specific focus on immunoglobulin isotypes and the microorganisms, pathogenic and non-pathogenic that interact with the immune system. PMID- 26995775 TI - Effect of genotype and age on some carcass and meat quality traits of beef carcasses subjected to the South African classification system. AB - Genotype and age effects on pH24, L*, a*, b*, tenderness (WBSF), cooking (CL %), and thawing loss (TL %) of beef carcasses subjected to the South African classification system were determined. Carcass traits (bruising, subcutaneous fat (SF), and conformation) were also measured. Meat quality measurements were taken on the longissimus thoracis et lumborum (n=175) of A, AB, B, and C carcasses from Angus, Bonsmara, Fleckvieh, Non-descript, and Simmental genotypes. No bruises were evident in all carcasses. All carcasses scored medium conformation (class 3) while in SF classification, class 2 had the greatest frequency (66.3%). Genotypic effects (P<0.05) were observed for a*, hue angle (HA), pH24, TL%, CL%, and WBSF between steers with six, seven, and eight incisors. Notable differences (P<0.05) were observed for tenderness where Angus and Simmental had least tender meat while Non-descript and Fleckvieh had the tenderest meat within the C-age class. Meat quality varied within animals of the same age-class across genotypes. PMID- 26995774 TI - Bio-preservative effect of the essential oil of the endemic Mentha piperita used alone and in combination with BacTN635 in stored minced beef meat. AB - The major compounds in Mentha piperita essential oil (EOMP) were menthol (33.59%) and iso-menthone (33%). The biopreservative effect of EOMP used alone at 0.25 or 0.5% and in combination with the semi-purified bacteriocin BacTN635 at 500 or 1000AU/g, on minced beef meat was evaluated by microbiological, physicochemical and sensory analyses during storage at 4 degrees C for 21days. EOMP used alone limited the microbial deterioration of minced meat (P<0.05). Furthermore, the combination between EOMP and BacTN635 led to a decrease in TBARS values and slowed down the accumulation of MetMb. This combination was more efficient (P<0.05) against microflora proliferation and enhanced the sensory acceptability extending thus the shelf life of meat beef by approximately 7days. On the basis of these results, physicochemical and sensorial parameters could be used for constructing regression models to predict overall acceptability. Overall, the strongest preservative effect was achieved by using the combination of EOMP at 0.5% with BacTN535 at 1000AU/g. PMID- 26995776 TI - The effect of open kinetic chain knee extensor resistance training at different training loads on anterior knee laxity in the uninjured. AB - BACKGROUND: The commonly used open kinetic chain knee extensor (OKCKE) exercise loads the sagittal restraints to knee anterior tibial translation. OBJECTIVE: To investigate the effect of different loads of OKCKE resistance training on anterior knee laxity (AKL) in the uninjured knee. STUDY DESIGN: non-clinical trial. METHODS: Randomization into one of three supervised training groups occurred with training 3 times per week for 12 weeks. Subjects in the LOW and HIGH groups performed OKCKE resistance training at loads of 2 sets of 20 repetition maximum (RM) and 20 sets of 2RM, respectively. Subjects in the isokinetic training group (ISOK) performed isokinetic OKCKE resistance training using 2 sets of 20 maximal efforts. AKL was measured using the KT2000 arthrometer with concurrent measurement of lateral hamstrings muscle activity at baseline, 6 weeks and 12 weeks. RESULTS: Twenty six subjects participated (LOW n = 9, HIGH n = 10, ISOK n = 7). The main finding from this study is that a 12-week OKCKE resistance training programme at loads of 20 sets of 2RM, leads to an increase in manual maximal AKL. CONCLUSIONS: OKCKE resistance training at high loads (20 sets of 2RM) increases AKL while low load OKCKE resistance training (2 sets of 20RM) and isokinetic OKCKE resistance training at 2 sets of 20RM does not. PMID- 26995777 TI - The effects of caudal mobilisation with movement (MWM) and caudal self mobilisation with movement (SMWM) in relation to restricted internal rotation in the hip: A randomised control pilot study. AB - BACKGROUND: A loss of internal rotation (IR) of the hip is associated with hip pathology. Improving IR may improve hip range of motion (ROM) or prevent hip pathology. OBJECTIVES: The purpose of this study was to compare the immediate effects of caudal mobilisation with movement (MWM) and caudal self-mobilisation with movement (SMWM) on young healthy male subjects with reduced IR of the hip. DESIGN: A randomised controlled trial was performed. Twenty-Two subjects were randomised into a MWM group (n = 6), SMWM group (n = 8) or a control group (n = 8). METHOD: The primary outcome measures included the functional internal rotation test (FIRT) for the hip and the passive seated internal rotation test (SIRT) for the hip. Outcomes were captured at baseline and immediately after one treatment of MWMs, SMWMs or control. RESULTS: A two-way analysis of variance (ANOVA), group * time interaction was conducted. The ANOVA revealed the only significant improvement was in the MWM group for the FIRT (p = 0.01), over the control group. Subjects with reduced IR of the hip who receive a single session of MWMs exhibited significantly improved functional IR of their hip than the control group. CONCLUSIONS: From the data presented, it can be suggested that caudal MWMs of the hip appear to have a positive effect on functional IR of healthy young hips. This may be due to addressing the positional fault theory or the arthrogenic muscular inhibition theory. SMWMs may be effective in augmenting treatments for patients waiting for hip operations. PMID- 26995778 TI - The immediate effect of lumbopelvic manipulation on EMG of vasti and gluteus medius in athletes with patellofemoral pain syndrome: A randomized controlled trial. AB - OBJECTIVE: To evaluate the immediate effect of lubmopelvic manipulation on EMG activity of vastus medialis, vastus lateralis and gluteus medius as well as pain and functional performance of athletes with patellofemoral pain syndrome. DESIGN: Randomized placebo-controlled trial. METHODS: Twenty eight athletes with patellofemoral pain syndrome were randomly assigned to two groups. One group received a lubmopelvic manipulation at the side of the involved knee while the other group received a sham manipulation. EMG activity of the vasti and gluteus medius were recorded before and after manipulation while performing a rocking on heel task. The functional abilities were evaluated using two tests: step-down and single-leg hop. Additionally, the pain intensity during the functional tests was assessed using a visual analog scale. RESULTS: The onset and amplitude of EMG activity from vastus medialis and gluteus medius were, respectively, earlier and higher in the manipulation group compared to the sham group. There were no significant differences, however, between two groups in EMG onset of vastus lateralis. While the scores of one-leg hop test were similar for both groups, significant improvement was observed in step-down test and pain intensity in the manipulation group compared to the sham group. CONCLUSIONS: Lubmopelvic manipulation might improve patellofemoral pain and functional level in athletes with patellofemoral pain syndrome. These effects could be due to the changes observed in EMG activity of gluteus medius and vasti muscles. Therefore, the lubmopelvic manipulation might be considered in the rehabilitation protocol of the athletes with patellofemoral pain syndrome. PMID- 26995779 TI - Endoscopic and Histological Findings Are Predicted by Fecal Calprotectin in Acute Intestinal Graft-Versus-Host-Disease. AB - BACKGROUND: Gastrointestinal graft-versus-host-disease (GI-GVHD) is a major cause of nonrelapse mortality after hematopoietic stem cell transplantation (HSCT) necessitating endoscopic examinations and biopsies for diagnosis. Fecal calprotectin (CPT) has been widely used in gastrointestinal inflammation, but comprehensive data in GI-GVHD are lacking. AIMS: We aimed to identify an association of CPT with endoscopic findings, mucosal damage and symptoms for diagnosing and monitoring acute GI-GVHD. METHODS: Symptoms were prospectively evaluated in 110 consecutive HSCT recipients by standardized questionnaires and Bristol Stool Scale (BSS). CPT was assayed by ELISA. Symptom assessment and CPT were performed weekly and with onset of first symptoms. GVHD was diagnosed according to the Glucksberg criteria and by endoscopic biopsies. Patients with GI GVHD received standard high-dose corticosteroid therapy and follow-up CPT, and symptom evaluation was performed after 28 days. Patients not responding to steroid treatment were re-evaluated by colonoscopy. RESULTS: GI-GVHD was diagnosed in 40 patients. Twelve patients with GI symptoms and CMV colitis and 24 patients with isolated skin GVHD were included as control subjects. CPT was significantly higher in GI-GVHD compared to skin GVHD and CMV colitis. Endoscopic findings, histological grading, abdominal cramps, diarrhea, urgency and BSS correlated with CPT. At follow-up, CPT correlated with abdominal cramps, diarrhea, urgency and BSS. In steroid refractory patients, CPT level was still significantly associated with severity of mucosal damage. CONCLUSION: CPT predicts endoscopic and histological findings in GI-GVHD and correlates with lower GI symptoms. It enables to discriminate GVHD from CMV colitis and to monitor therapeutic success. PMID- 26995780 TI - Insulin Resistance as a Novel Risk Factor for Post-ERCP Pancreatitis: A Pilot Study. AB - BACKGROUND AND AIMS: The relationship between insulin resistance and post-ERCP pancreatitis (PEP) is not known. We aimed to determine the relation between pre ERCP insulin resistance and risk of PEP, and to evaluate the relationship of insulin resistance with well-established risk factors for PEP. METHODS: Consecutive patients who underwent ERCP with the diagnosis of choledocolithiasis between January and December 2013 were enrolled in this prospective study. Pre procedural insulin resistance state and other risk factors were evaluated according to PEP development. RESULTS: Pancreatitis developed in 16 (11.3 %) of 141 ERCP procedure. Homeostasis model assessment of insulin resistance (HOMA-IR) levels was found statistically significantly higher in patients who developed PEP than the ones who did not (3.37 +/- 0.8 vs. 2.38 +/- 1.4, p < 0.001). Common bile duct (CBD) diameter of the patients developing PEP was found significantly lower than the non-PEP group (10.1 +/- 4 vs. 13.4 +/- 4.5 mm, p = 0.01). Mean procedure time was 33.5 min in PEP group and 27.9 min in non-PEP group (p = 0.006). HOMA-IR (OR 2.39), procedure time (OR 1.15), and CBD diameter (OR 0.82) were independent predictors of PEP development. CONCLUSIONS: The presence of insulin resistance is an important risk factor for PEP, and these data can be used as a considerable clue to predict the risk of PEP before ERCP and to decrease related morbidity. PMID- 26995781 TI - Swarming motility is modulated by expression of the putative xenosiderophore transporter SppR-SppABCD in Pseudomonas aeruginosa PA14. AB - In the present study, we characterised the putative peptide ABC transporter SppABCD, which is co-transcribed with the TonB-dependent receptor SppR in Pseudomonas aeruginosa PA14. However, our data show that this transporter complex is not involved in the uptake of peptides. The fact that the TonB-dependent receptor SppR is regulated by an iron starvation ECF sigma factor suggested that this transporter is probably involved in the uptake of xenosiderophores. Therefore, we screened culture supernatants of 23 siderophore-producing bacteria for their ability to induce the expression of the SppR-regulating ECF sigma factor. However, none of them had an effect on the expression of this ECF sigma factor. Since the spp operon is not expressed under standard laboratory conditions, we overexpressed it from plasmids in PA14, which led to an impairment of its swarming motility on semisolid agar. Since we excluded the possibility that the uptake of a culture medium component was responsible for the observed phenotype, we hypothesize that the Spp transport system is involved in the uptake of a compound from the periplasmic space or a compound secreted by P. aeruginosa. Furthermore, we found that rhamnolipid synthesis was decreased while biofilm and exopolysaccharide synthesis was slightly increased upon overexpression of the spp operon. Moreover, we observed an impact of spp overexpression on regulation of genes involved in siderophore and phenazine biosynthesis. PMID- 26995782 TI - Study of heat-stress levels in naturally ventilated sheep barns during heat waves: development and assessment of regression models. AB - It is well documented that heat-stress burdens sheep welfare and productivity. Peak heat-stress levels are observed when high temperatures prevail, i.e. during heat waves; however, continuous measurements inside livestock buildings are not usually available for long periods so as to study the variation of summer heat stress levels for several years, especially during extreme hot weather. Alpha methodology to develop a long time series of summer temperature and relative humidity inside naturally ventilated sheep barns is proposed. The accuracy and the transferability of the developed linear regression models were verified. Temperature Humidity Index (THI) was used to assess sheep's potential heat stress. Tauhe variation of THI inside a barn during heat wave and non-heat wave days was examined, and the results were comparatively assessed. The analysis showed that sheep were exposed to moderate, severe, and extreme severe heat stress in 10, 21 and 66 % of hours, respectively, during heat wave days, while the corresponding values during non-heat wave days were 14, 33 and 43 %, respectively. The heat load on sheep was much higher during heat wave events than during non-heat wave periods. Additionally, based on the averaged diurnal variation of THI, it was concluded that extreme severe heat-stress conditions were prevailing between 1000 and 2400 hours local time during heat wave days. Cool off night periods were never and extremely rarely detected during heat wave and non-heat wave days, respectively. PMID- 26995784 TI - Supersize my brain: A cross-sectional voxel-based morphometry study on the association between self-reported dietary restraint and regional grey matter volumes. AB - Restrained eaters do not eat less than their unrestrained counterparts. Proposed underlying mechanisms are that restrained eaters are more reward sensitive and that they have worse inhibitory control. Although fMRI studies assessed these mechanisms, it is unknown how brain anatomy relates to dietary restraint. Voxel based morphometry was performed on anatomical scans from 155 normal-weight females to investigate how regional grey matter volume correlates with restraint. A positive correlation was found in several areas, including the parahippocampal gyrus, hippocampus, striatum and the amygdala (bilaterally, p<0.05, corrected). A negative correlation was found in several areas, including the inferior frontal gyrus, superior frontal gyrus, supplementary motor area, middle cingulate cortex and precentral gyrus (p<0.05, corrected). That higher restraint relates to higher grey matter volume in reward-related areas and lower grey matter volume in regions involved in inhibition, provides a neuroanatomical underpinning of theories relating restraint to increased reward sensitivity and reduced inhibitory capacity. PMID- 26995785 TI - Effects of emotional intensity under perceptual load: An event-related potentials (ERPs) study. AB - Effects of emotional intensity and valence on visual event-related potentials (ERPs) are still poorly understood, in particular in the context of limited attentional resources. In the present EEG study, we investigated the effect of emotional intensity of different emotional facial expressions on P1, N170, early posterior negativity (EPN) and late positive potential (LPP) while varying the amount of available attentional resources. A new stimulus set comprising 90 full color pictures of neutral, happy (low, high intensity), and angry (low, high intensity) expressions was developed. These facial expressions were presented centrally, superimposed by two horizontal bars, and participants engaged in a focal bars task. Availability of attentional resources was varied in two conditions by manipulating the difficulty of the focal bars task (low vs. high perceptual load). Our findings demonstrate intensity and valence effects of task irrelevant facial expressions on early (N170) and intermediate processing stages (EPN). In addition, task-related effects of perceptual load evolved at intermediate processing stages and were full blown in the time window of LPP. In line with limited resource accounts, valence effects on N170 and EPN were reduced under high perceptual load. Interestingly, apart from this valence by load interaction no further interactions between stimulus and task-driven factors were obtained: Effects of emotional intensity were not modulated by the perceptual load of the focal bars task, indicating that emotional intensity was processed even though attentional resources were heavily restricted. PMID- 26995783 TI - Structural Insight for Roles of DR5 Death Domain Mutations on Oligomerization of DR5 Death Domain-FADD Complex in the Death-Inducing Signaling Complex Formation: A Computational Study. AB - Death receptor 5 (DR5)-induced apoptosis that prioritizes the death of tumor cells has been proposed as one of the promising cancer therapies. In this process, oligomerized DR5 death domain (DD) binding to Fas-associated death domain (FADD) leads to FADD activating caspase-8, which marks the formation of the death-inducing signaling complex (DISC) that initiates apoptosis. DR5 DD mutations found in cancer cells have been suggested to play an important pathological role, the mechanism through which those mutants prevent the DR5 activated DISC formation is not clear yet. This study sought to provide structural and molecular insight for the roles of four selected DR5 DD mutations (E355K, E367K, K415N, and L363F) in the oligomerization of DR5 DD-FADD complex during the DISC formation. Results from the molecular dynamics simulations show that the simulated mutants induce conformational, dynamical motions and interactions changes in the DR5 DD-FADD tetramer complex, including changes in a protein's backbone flexibility, less exposure of FADD DED's caspase-8 binding site, reduced H-bonding and hydrophobic contacts at the DR5 DD-FADD DD binding, altered distribution of the electrostatic potentials and correlated motions of residues, and reduced binding affinity of DR5 DD binding to FADD. This study provides structural and molecular insight for the influence of DR5 DD mutations on oligomerization of DR5 DD-FADD complex, which is expected to foster understanding of the DR5 DD mutants' resistance mechanism against DR5-activated DISC formation. PMID- 26995786 TI - Components of inhibition in autogenous- and reactive-type obsessive-compulsive disorder: Dissociation of interference control. AB - Obsessive-compulsive disorder (OCD) is characterized by unwanted, intrusive thoughts (obsessions) and/or repetitive, ritualistic behaviors (compulsions). Findings related to the two components of inhibition, namely interference control and behavioral inhibition, among OCD patients have been inconsistent. It might be that this inconsistency is due to the heterogeneity among OCD cases representing multiple subtypes of OCD, such as autogenous obsessions and reactive obsessions types (AOs vs. ROs). AOs and ROs are distinguished by the category of their most disturbing obsessions. The purpose of this study was to systematically examine whether inhibition functions differ between AO and RO patients. We assessed interference control and behavioral inhibition with the emotional Stroop task (EST) and stop-signal task (SST), respectively, in 42 AOs, 55 ROs and 62 healthy controls (HCs) and event-related potentials (ERPs) were recorded in a random subset of these subjects (25 AOs, 25 ROs, and 31HCs). Results showed that in the EST, AOs exhibited longer reaction times (RTs) for color-naming positive-, negative-, and neutral-valence word stimulus than both ROs and HCs, and demonstrated larger P2 and less negative N450 amplitudes than HCs and larger P3 amplitudes than ROs and HCs. In the SST, both AOs and ROs showed lengthened stop signal reaction time (SSRT) and reduced Stop-P3 amplitudes in successful inhibition (SI) trials compared to the HC group. These present findings suggest that behavioral inhibition impairment may reflect a common pathology in both the autogenous- and reactive-type OCD patients, whereas interference inhibition impairment appears to be specific to patients with autogenous obsessions. These findings strengthened the insight into the clinical heterogeneity and pathophysiology of OCD. PMID- 26995787 TI - Lies that feel honest: Dissociating between incentive and deviance processing when evaluating dishonesty. AB - This study investigated neural responses to evaluations of lies made by others. Participants learned about other individuals who were instructed to privately roll a die twice and report the outcome of the first roll to determine their pay (with higher rolls leading to higher pay). Participants evaluated three types of outcomes: honest reports, justifiable lies (reporting the second outcome instead of the first), or unjustifiable lies (reporting a different outcome than both die rolls). Evaluating lies relative to honest reports was associated with increased activation in the anterior cingulate cortex (ACC), insula and lateral prefrontal cortex. Moreover, justifiable lies were associated with even stronger activity in the dorsal ACC and dorsolateral prefrontal cortex compared to unjustifiable lies. These activities were more pronounced for justifiable lies where the deviance from the real outcome was larger. Together, these findings have implications for understanding how humans judge misconduct behavior of others. PMID- 26995789 TI - A malignant cellular network in gliomas: potential clinical implications. AB - The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly in astrocytomas, extends our understanding of how these tumors progress in the brain and how they resist therapies. In this article, we will focus on ideas on how to target these membrane protrusions, for which we have suggested the term "tumor microtubes" (TMs), and the malignant multicellular network they form. First, we discuss TM-specific features and their differential biological functions known so far. Second, the connection between 1p/19q codeletion and the inability to form functional TMs via certain neurodevelopmental pathways is presented; this could provide an explanation for the distinct clinical features of oligodendrogliomas. Third, the role of TMs for primary and potentially also adaptive resistance to cytotoxic therapies is highlighted. Fourth, avenues for therapeutic approaches to inhibit TM formation and/or function are discussed, with a focus on disruption (or exploitation) of network functionality. Finally, we propose ideas on how to use TMs as a biomarker in glioma patients. An increasing understanding of TMs in clinical and preclinical settings will show us whether they really are a long-sought-after Achilles' heel of treatment-resistant gliomas. PMID- 26995792 TI - Is the E-Liquid Industry Regulating Itself? A Look at E-Liquid Internet Vendors in the United States. AB - INTRODUCTION: The objective of this study was to assess whether the nascent, but rapidly growing e-liquid industry prohibits Internet sales to minors and employs safety measures to prevent accidental poisonings. METHODS: A stratified simple random sample (n = 120) was selected from the target population (N = 1107) of US online vendors of e-liquid in July 2015. The vendors were stratified and subsequently oversampled by trade association membership and vendor popularity. Three minors aged 16 to 17, who were supervised by adult research staff, attempted to purchase e-liquid from the 120 online vendors using debit cards issued in their names. Measures included vendors' use of age verification, warning labels on e-liquid bottles, and child-resistant packaging. RESULTS: Statistically significant differences were observed by vendor popularity, but not by membership in a trade association. The differences by vendor popularity, however, occurred for measures that were limited to an age warning and list of ingredients. The most striking finding was the scant vendors (n = 4) who successfully prevented the sale of e-liquid to the minors. In contrast, 87.5% and 53.9% of the bottles contained child-resistant packaging and a health warning label, respectively. CONCLUSIONS: Irrespective of trade association membership or vendor popularity, online vendors of e-liquids are not taking the proper precautions in preventing sales to minors. The FDA's upcoming deeming rules on e cigarette products should include explicit requirements for offline and online e liquid vendors, particularly the use of effective age verification, warning labels, and child-resistant packaging. IMPLICATIONS: This study demonstrates that, in the absence of any current FDA regulation of e-liquid products, self regulation among vendors is not effective in preventing product acquisition by minors. Lax oversight of the e-liquid industry may draw consumers to bypass current tobacco control restrictions implemented in face-to-face sales settings. As a consequence, there may be an increase in online sales to minors. Further regulation of the industry may increase the already prevalent use of child resistant packaging, leading to fewer cases of accidental nicotine poisoning. PMID- 26995790 TI - Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel. AB - BACKGROUND: We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. METHODS: The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. RESULTS: Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. CONCLUSIONS: Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. PMID- 26995793 TI - Trends and Factors Related to Smokeless Tobacco Use in the United States. AB - BACKGROUND: While declines in smoking prevalence in the United States have been well documented, trends in smokeless tobacco (SLT) use are less clear. This study updates previous analyses of US SLT use prevalence to better understand trends and factors related to SLT use. METHODS: We used the Tobacco Use Supplement of the Current Population Survey (TUS-CPS) to examine trends and factors related to SLT use using joinpoint and logistic regression models. SLT consumption from 1985 to 2011 was obtained from the 2011 Federal Trade Commission Smokeless Tobacco Report. Sensitivity analyses were conducted for assessing the impact of varying frequency definitions of SLT use. RESULTS: Decreasing trends in smoking and SLT prevalence overall were observed from 1992 to 2003 independently of use definition. SLT prevalence in the total adult population significantly decreased at an annual percent change (APC) of 4.5% per year from 1992 to 2003, but has been approximately constant ever since. Similar patterns were also found in adult males (APC = -4.4%) and young males (APC = -9.5%). SLT per capita consumption decreased significantly from 1991 to 1999 (APC = -2.2%), but has since decreased at only 0.35% per year (1999-2011). SLT use was found to be associated with former smoker status, younger age, white race, living in rural areas, residence in the South, lower education and unemployment, adjusting for other factors. CONCLUSIONS: Declines in SLT use were found in the United States, suggesting tobacco control has had positive impacts, but these have slowed since 2003. Targeting tobacco control policies to at-risk demographic groups is needed to further reduce SLT use in the United States. IMPLICATIONS: This study confirms that the declines in SLT use prevalence stopped in 2003 across different demographic groups, consistent with trends in SLT consumption. In addition, the longer period of analysis in comparison with earlier studies allows for quantitative characterization of SLT use trends using joinpoint regression. The study also shows the impact of different SLT use definitions in determining tobacco product use prevalence and trends. PMID- 26995794 TI - Smoking Topography Characteristics of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls. AB - INTRODUCTION: Reducing the nicotine content of cigarettes to a minimally addictive level has been proposed as a regulatory strategy for reducing tobacco dependence. However, smokers with schizophrenia (SS) may be prone to changing their smoking topography in efforts to compensate for the reduction in nicotine content. The aims of this study were to compare smoking topography characteristics of usual-brand and very low nicotine content (VLNC) cigarettes in SS and control smokers without psychiatric illness (CS), and to determine whether nicotine replacement reversed any changes in topography produced by VLNC cigarettes. METHODS: Using a within-subjects, counter-balanced design, SS (n = 27) and CS (n = 23) smoked usual brand cigarettes, VLNC cigarettes while wearing placebo patches (VLNC + PLA), or VLNC cigarettes while wearing transdermal nicotine patches totaling 42mg (VLNC + NIC) during 5-hour ad libitum smoking sessions. Cigarettes were smoked through topography measurement devices. RESULTS: Across conditions, SS smoked more puffs per session and per cigarette, had higher cigarette volumes, and had shorter inter-puff intervals than CS (Ps < .01). During VLNC cigarette sessions, puff duration increased and time between puffs decreased, but participants smoked fewer puffs, resulting in a net decrease in cigarette and total session volume (Ps < .001). There were no significant interactions between group and condition. CONCLUSIONS: These findings indicate that acute use of VLNC cigarettes does not increase intensity of smoking in SS, and support the feasibility of a nicotine reduction policy. IMPLICATIONS: Reducing the nicotine in cigarettes to a minimally addictive level has been proposed as a means of reducing tobacco dependence. However, smokers, particularly those with schizophrenia (SS) may alter their puffing in an attempt to extract more nicotine from VLNC cigarettes. This study compared smoking topography of usual brand versus VLNC cigarettes, combined with placebo or transdermal nicotine patches, in SS and controls. Although some changes in topography were indicative of compensatory smoking, total puffs and total cigarette volume were reduced with VLNC cigarettes, indicating that acute VLNC cigarette use does not increase smoking in SS. PMID- 26995795 TI - Spring Breaks and Cigarette Tax Noncompliance: Evidence From a New York City College Sample. AB - OBJECTIVE: Estimate cigarette tax noncompliance (tax avoidance and evasion) before and after mid-semester recesses in a New York City college campus, where the majority of students are residents of nearby lower-tax states, using data derived from garbology, an archaeological method that reconstructs patterns of human behavior from discarded materials. DESIGN: We systematically divided the college campus into four geographic areas and established a total of 12 transects (survey lines) and five quadrats (survey spheres) in those areas to encompass 74 outdoor trash cans. Weekly collections of discarded cigarette packs (n = 174) in the four areas during Spring 2012 and 2013 were conducted to quantify the percentage of cigarette packs that were tax noncompliant. RESULTS: Overall, we find that 72.4% of the cigarette packs collected in Spring 2012 and 2013 did not bear the required joint New York City and New York State tax stamp. Additionally, we find that cigarette tax avoidance significantly increased after recesses (mid March and early April) in Spring 2012 and subsequently declined. We also find that packs with a Virginia tax stamp became more prevalent as time elapsed after each recess. CONCLUSION: College students practice tax avoidance, drawing on legal purchases from their own home states as the primary source of cheap cigarettes. As stocks decline, some students shift to tax evasion by illegally purchasing cigarettes in New York City that have been bootlegged from low tax states (eg, Virginia). IMPLICATIONS: Our study adds to the growing literature on cigarette tax noncompliance (ie, tax avoidance and evasion). First, we provide evidence that college students in our New York City sample avoid the payment of taxes in high tax states by purchasing low taxed cigarettes in their home state. Second, we find that once those sources are depleted, students find access to the black market nearby campus. This black market functions through cigarette tax evasion: the resale of cigarettes purchased in low tax states. Our study suggests that institutions of higher education operating in states with high cigarette taxes and a student body that resides in lower tax states should increase cessation services prior to breaks to discourage bulk purchases of cheap cigarettes. PMID- 26995797 TI - Mathematical Validation and Credibility of Diagnostic Blocks for Spinal Pain. AB - BACKGROUND: Diagnostic blocks are used in different ways for the diagnosis of spinal pain, but their validity has not been fully evaluated. METHODS: Four clinical protocols were analyzed mathematically to determine the probability of correct responses arising by chance. The complement of this probability was adopted as a measure of the credibility of correct responses. RESULTS: The credibility of responses varied from 50% to 95%, and was determined less by the agents used but more by what information was given to patients and if the agents were fully randomized for each block. CONCLUSIONS: Randomized, comparative local anesthetic blocks offer a credibility of 75%, but randomized, placebo-controlled blocks provide a credibility of 95%, and are thereby suitable as a criterion standard for diagnostic blocks. PMID- 26995796 TI - Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral Relaxing Imagery Differs Between Smokers and Nonsmokers. AB - INTRODUCTION: Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. METHODS: The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. RESULTS: During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. CONCLUSIONS: These findings provide data-driven insights into smoking related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. IMPLICATIONS: This study uses a data driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention, reward-related, emotional, and motivational processes. For smokers, these differences in connectivity may impact appetite, stress, and relaxation, and may interfere with smoking cessation. PMID- 26995798 TI - Using a New Measurement to Evaluate Pain Relief Among Cancer Inpatients with Clinically Significant Pain Based on a Nursing Information System: A Three-Year Hospital-Based Study. AB - OBJECTIVE: Developing a new measurement index is the first step in evaluating pain relief outcomes. Although the percentage difference in pain intensity (%PID) is the most popular indicator, this indicator does not take into account the goal of pain relief. Therefore, the aims of this study were to develop a pain relief index (PRI) for outcome evaluation and to examine the index using demographic characteristics of cancer inpatients with clinically significant pain. DESIGN: Retrospective cohort study. SETTING: A national hospital. SUBJECTS: All cancer inpatients. METHODS: Pain intensity was assessed using a numerical rating scale, a faces pain scale or the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Tool. Using a nursing information system, a pain score database containing data from 2011 through 2013 was analyzed. RESULTS: Cancer patients representing 93,812 hospitalizations were considered in this study. We focused on cancer patients for whom the worst pain intensity (WPI) was >= 4 points. PRI values of -62.02% to -72.55% were observed in the WPI >= 7 and 4 <= WPI <= 6 groups. Significant (P < 0.05) effects on PRI values were observed among patients who were > 65 years old, those who were admitted to the medicine or gynecology and those who had a hospital stay > 30 days. CONCLUSION: This hospital-based study demonstrated that the PRI is an effective and valid measure for evaluating outcome data using an electronic nursing information system. We will further define the meaningful range of percentage difference in PRI from various perspectives. PMID- 26995799 TI - SoluMatrix(r) Diclofenac: Sustained Opioid-Sparing Effects in a Phase 3 Study in Patients with Postoperative Pain. AB - OBJECTIVES: To evaluate opioid rescue medication usage and the opioid-sparing effect of low-dose SoluMatrix(r) diclofenac developed using SoluMatrix Fine Particle TechnologyTM in a phase 3 study in patients experiencing pain following bunionectomy surgery. DESIGN: Multicenter, randomized, double-blind, parallel group study (NCT01462435). SETTING: Four clinical research centers in the United States. SUBJECTS: Four hundred twenty-eight patients aged 18 to 65 years who experienced moderate-to-severe pain following bunionectomy surgery. METHODS: Patients were randomized to receive low-dose SoluMatrix diclofenac 35 mg or 18 mg capsules three times daily (35-mg group or 18-mg group), celecoxib 400 mg loading dose followed by 200-mg capsules twice daily (celecoxib 200-mg group), or placebo capsules postsurgery. Patients were permitted to receive opioid-containing rescue medication as needed. RESULTS: Significantly fewer patients who received SoluMatrix diclofenac 35 mg or 18 mg or celecoxib required rescue medication during 0-24 h and >24-48 h postsurgery compared with placebo. Patients in the SoluMatrix diclofenac 35 mg or 18 mg groups or in the celecoxib group used fewer mean rescue medication tablets over 0-24 h and >24-48 h compared with placebo treated patients. Patients in the SoluMatrix diclofenac 35 mg and 18 mg groups and in the celecoxib group also required rescue medication at later times and at slower rates compared with placebo-treated patients. No serious adverse effects occurred in patients receiving SoluMatrix diclofenac. CONCLUSIONS: SoluMatrix diclofenac at two dosage strengths demonstrated an opioid-sparing effect postoperatively in this phase 3 study. SUMMARY: The opioid-sparing effect following low-dose SoluMatrix diclofenac (35 mg or 18 mg three times daily) administration was evaluated in patients experiencing pain following bunionectomy. Significantly fewer patients receiving SoluMatrix diclofenac or celecoxib (400 mg loading, 200 mg twice daily) required rescue medication during 0-24 h and >24-48 h following bunionectomy compared with placebo. No serious adverse events were reported among patients who received SoluMatrix diclofenac. SoluMatrix diclofenac may reduce opioid usage in the postoperative setting in patients with acute pain. PMID- 26995801 TI - "Piriformis Syndrome": Is It Only Piriformis? PMID- 26995800 TI - The Impact of Prescription Drug Monitoring Programs and Prescribing Guidelines on Emergency Department Opioid Prescribing: A Multi-Center Survey. AB - Objective: Emergency department (ED) providers are high volume but low quantity prescribers of opioid analgesics (OA). Few studies have examined differences in opioid prescribing decisions specifically among ED providers. The aim of this study was to describe OA prescribing decisions of ED providers at geographically diverse centers, including utilization of prescribing guidelines and prescription drug monitoring programs (PDMP). Methods: This was a multi-center cross-sectional Web-based survey of ED providers who prescribe OA. Respondents were asked about their OA prescribing decisions, their use of PDMPs, and their use of prescribing guidelines. Data was analyzed using descriptive statistics and chi-square tests of association were used to assess the relationship between providers' opioid prescribing decisions and independent covariates. Results: The total survey population was 957 individuals and 515 responded to the survey for an overall response rate of 54%. The frequency respondents prescribed different types of pain medication was variable between centers. of respondents were registered to access a PDMP, and were not aware whether their state had a PDMP. Forty percent (172/426) of respondents used OA prescribing guidelines, while 24% (103/426) did not, and 35% (151/426) were unaware of prescribing guidelines. No significant differences in OA prescribing decisions were found between groups either by use of PDMP or by guideline adherence. Conclusions: In this multi-center survey study of ED clinicians, OA prescribing varied between centers The utilization of prescribing guidelines and PDMPs was not associated with differences in OA prescribing decisions. PMID- 26995802 TI - Global and Situational Relationship Satisfaction Moderate the Effect of Threat on Pain in Couples. AB - OBJECTIVE: The aim of this study was to test the hypothesis that greater global and situational relationship satisfaction would reduce the negative impact of threatening information on acute pain. DESIGN: An experimental design was used to manipulate threat and elicit acute pain via a cold pressor task. SETTING: The study was completed in a research laboratory at a large urban university in the Midwestern USA. SUBJECTS: Participants were 134 couples, in which at least one individual was an undergraduate student. METHODS: After administration of a global relationship satisfaction measure, couples were randomly assigned to either receive high or low threatening information about the painful task. Following the threat manipulation, couples discussed the upcoming task and rated their satisfaction with the interaction (i.e., situational relationship satisfaction). The designated pain participant then completed the painful task alone. RESULTS: The threat manipulation altered couples' perceived threat of pain. Situational relationship satisfaction moderated the effect of threat on pain trajectories such that situational relationship satisfaction predicted less pain intensity at an earlier point in the task for the low threat condition than the high threat condition. Greater global relationship satisfaction predicted greater likelihood of task completion among those in the low threat condition, whereas it was unrelated to task completion in the high threat condition. Greater global relationship satisfaction also predicted lower pain intensity throughout the task. CONCLUSIONS: These findings demonstrate that the interpersonal context is independently related to acute pain and may also alter the effect of threatening information on acute pain. PMID- 26995803 TI - Kantso et al (J Infect Dis 2015; 212:1093-9). PMID- 26995804 TI - Zoonotic influenza viruses: antigenic and genetic characteristics and development of candidate vaccine viruses for pandemic preparedness. PMID- 26995805 TI - [Observations of movements of lymphy vessels in patients with lymphedema of the limbs]. AB - The authors report own observations on the spontaneous active movements of lymph vessels in man. Two cases of lymphedema of the lower limb are presented in which these movements of lymph vessels were observed during lymphography and after surgical exposure during the operation of a lympho-venous anastomosis. PMID- 26995806 TI - The combination of non-selective NSAID 400 mg and paracetamol 1000 mg is more effective than each drug alone for treatment of acute pain. A systematic review. AB - The aim was to evaluate the evidence on outcomes of the combination of non selective NSAID/ paracetamol compared to either drug alone, to relieve acute pain following oral surgery in adult patients. A systematic review of available literature was performed. The first step comprised searches in three electronic databases. Original studies written in English were searched. As a second step, the reference lists of included publications were searched for additional publications. Abstracts were retrieved if the title contained information on postoperative pain, NSAID, and paracetamol in combination with oral surgery. Two reviewers selected publications on the basis of predetermined inclusion criteria. Data were extracted using one protocol and the quality of each study was assessed using another protocol. The initial search in PubMed resulted in 138 abstracts and in the Cochrane library a further four. The search in the Web of Science resulted in no additional abstract. Five RCTs fulfilled the inclusion criteria. Pain relief from the combination of non-selective NSAID with paracetamol was significantly better than with paracetamol alone as well as with NSAID alone. Nausea, vomiting, headache, and dizziness were among the most common adverse events in all treatment groups. Most of the adverse events were of mild to moderate severity. Two studies reported no significant differences in adverse events between the treatment groups. According to one study the adverse events were significantly lower for the combination ibuprofen 400 mg/paracetamol 1000 mg compared to ibuprofen 400 mg alone. The need for rescue drugs in the different groups varied between the studies. Since the studies reported a significantly better postoperative pain relief with the combination of non-selective NSAIDs/paracetamol compared to each drug alone, this combination might be considered the treatment of choice, as long as side effects of NSAIDs are observed. PMID- 26995807 TI - The adoption of nickel-titanium rotary instrumentation increases root-filling quality amongst a group of Swedish general dental practitioners. AB - The aim of the present study was testing the hypothesis that the adoption of nickel-titanium rotary instrumentation (NTRI) will improve the technical quality of root-fillings. The investigation was carried out within a mandatory continuing education program (CEP) for general dental practitioners (GDPs). The study was conducted amongst GDPs employed by the Public Dental Health Service in the County of Stockholm. Identical questionnaires were distributed before the CEP (Pre-Q) and 9 to 12 months after the course (Post-Q). The CEP consisted of two parts: lectures and hands-on training. From each GDP, radiographs of two cases completed before the course and two cases treated 9-12 months after the course were randomly selected. Primarily molars were selected for evaluation. The radiographs were individually evaluated by two endodontists. Teeth treated before and after training were presented in random order. Adoption rate of NTRI increased from 35% to 75%. Cases from 124 GDPs were included in the final analysis. The rate of good quality root-fillings increased from 27% to 49% (p<.001). A significantly increased radiographic quality was found between GDPs adopting NTRI and those who did not. The GDPs produced root-fillings of very poor quality before as well as after the training period. However, the rate decreased from 29% to 12% amongst adopters and from 46% to 28% amongst non-adopters. Dentists considering canal preparation and root-filling as "easy" produced more frequently good quality root fillings than the others (p<0.05). In conclusion, the results of the present study were in favour of the idea that a shift to NTRI increases the technical quality of root-fillings produced by GDPs. However, adopters still produce root fillings of very poor quality. This important issue needs to be addressed in future studies. PMID- 26995808 TI - Titanium- and zirconia-based implant-supported fixed dental prostheses. A randomized, prospective clinical pilot study. AB - The aim of this study was to compare porcelain-veneered implant-supported FDPs based on zirconium dioxide and titanium respectively. Sixteen patients received 18 implant-supported partial fixed dental prostheses (FDPs); 8 titanium-based and 10 zirconia-based. The FDPs were randomized between the two material groups. Follow-up of the patients was performed at 3 months and thereafter once a year. An assessment protocol based on the California Dental Association (CDA) quality assessment system was used. Results: All patients were seen at follow-up. The mean time of clinical service at follow-up was 15,2 months (range 12-24 months). All restorations were in place and all patients were satisfied with the treatment. No technical complications were noted in either group. Minor biological complications, in the form of plaque and/or mucositis, not affecting the survival of the restorations were noted for six of the titanium-based restorations and two of the zirconia-based restorations. The difference between the two material groups was not statistically significant. The outcomes of both materials were comparable. Short term data from this study suggests that porcelain-veneered implant-supported partial FDPs based on zirconia and titanium are satisfactory and equal treatment options. This conclusion is however preliminary as it is based on a small number of patients and short-term follow up. Long-term follow-up of larger groups of patients is needed before more definite conclusions can be made. PMID- 26995809 TI - Positioning errors in panoramic images in general dentistry in Sormland County, Sweden. AB - The purpose of this study was to evaluate the frequency and severity of positioning errors in panoramic radiography in general dentistry. A total of 1904 digital panoramic radiographs, taken by the Public Dental Service in the county of Sormland, Sweden, were analysed retrospectively. The study population consisted of all patients who underwent a panoramic examination during the year 2011. One experienced oral radiologist evaluated all radiographs for 10 common errors. Of the 1904 radiographs examined, 79 per cent had errors. The number of errors varied between 1-4 errors per image. No errors were found in 404 images (21%). Fifty-five images (3%) had severe errors, which made it impossible to make correct diagnostics. The most common error was the tongue not being in contact with the hard palate during exposure. However, this did not greatly affect the diagnostic usefulness of the image due to the ability to enhance the image.The patient's head was tilted too far upwards in 23 per cent of the images and the patient's head was rotated during exposure in 15 per cent. The least common error was due to patient movement during exposure (1%). Panoramic radiographs taken in general dental clinics in a Swedish county show several errors. Proper positioning of the patient is necessary to achieve panoramic images with good image quality. Some of the errors could be adjusted with the digital technique used.This allowed assessment of the images, which reduces radiation dose by avoiding retakes. PMID- 26995810 TI - A long-term controlled follow-up study of objective treatment need on young adults treated with functional appliances. AB - The aims of this study were to 1) evaluate the objective success rate of Class II malocclusion treatment with functional appliances five years after completion of treatment and 2) to compare the remaining objective treatment need with an untreated control group. Records of all listed patients between 18-20 years (n=1054) treated in a general practice were reviewed for the purpose of finding treatments with removable functional appliances. Among all subjects (n=61) who previously had been treated, 58 accepted to participate in the study.The test group was matched with an orthodontically untreated group with no history of objective treatment need. Clinical examination was performed and study casts and photos were taken from both groups.The objective treatment need was evaluated through clinical examination and study cast analysis with weighted Peer Assessment Rating index (wPAR). Twenty patients, (34.5%) (mean wPAR 13.8), succeeded with the functional appliance treatment.The wPAR score (mean 15.0) of the entire test group was significantly higher than the one of the control group (mean 7.3).The group that was treated exclusively with functional appliances had a mean wPAR score of 17.4. Eighteen patients (31.0%) who received retreatment with fixed appliances had a slightly higher mean wPAR (8.6) than the control group. Treatments with functional appliances in a general practice showed a high failure rate and a remaining treatment need. It is the treating dentist's responsibility to motivate the patient to cooperate to the treatment, because as it previously has been shown the treatment with functional appliances is a well functioning treatment alternative with the cooperation of the patient being sufficient. It is also of importance, already before starting treatment, to estimate the child's cooperation ability and to avoid treatment with removable appliances if the child or parents are reluctant about such a treatment. PMID- 26995811 TI - An explorative analysis of the recruitment of patients to a randomised controlled trial in adolescents with dental anxiety. AB - Randomised controlled trials (RCTs) are considered to provide the most reliable evidence on the efficacy of interventions. The aim of this study was to describe the recruitment process of an RCT study set up to evaluate a Cognitive Behavioural Therapy (CBT) intervention programme for adolescent patients with dental anxiety (DA). The participants were recruited from a consecutive sample of adolescent patients (12-19 yrs old) referred for DA to a specialised pediatric dentistry clinic. Age, gender, and reason for referral were recorded for the possible eligible patients as part of the drop-out analysis of the recruitment process. Participants were then randomized to the intervention (CBT integrated with dental treatment) or control (adapted dental treatment) condition. In the recruitment process, 138 possible eligible patients met inclusion criteria, of these 55 were enrolled, 44 declined participation and 39 patients were excluded.The patients enrolled in the RCT did not differ from the non participants with regard to age, gender or cause of referral. As a result of difficulties in the recruitment process, the study period was extended. The considerable proportion of non-participants as evident from the recruitment process may pose a threat to the external validity of the clinical trial. From a clinical perspective, the reasons for the lack of motivation to participate in behavioural interventions and the failure to appear warrant further investigation. PMID- 26995812 TI - [Many faces of phosphate]. PMID- 26995814 TI - [For the health of the people of Quebec]. PMID- 26995813 TI - [In memory of Dr. Janos Andras Szilard]. PMID- 26995815 TI - [Claude Morency from Mont Blanc to the North Pole]. PMID- 26995816 TI - [Men are late to consult]. PMID- 26995817 TI - [Taking action in the workplace]. PMID- 26995818 TI - [Fentanyl as street drug]. PMID- 26995819 TI - [Diane Arla. A nurse clinician helping vulnerable children]. PMID- 26995820 TI - [Adolescent suicidal crisis. The security plan]. PMID- 26995821 TI - [From CSSS to CISSS]. PMID- 26995822 TI - [Prevention of osteoporotic fractures]. PMID- 26995824 TI - [Caring for immigrant mothers]. PMID- 26995823 TI - [Integrating nurse practitioners in primary care]. PMID- 26995825 TI - [The law and end of life care. Role and responsibility of the nurse]. PMID- 26995826 TI - Embracing Change. PMID- 26995827 TI - The Oral-Psychiatric Link. PMID- 26995829 TI - LSKI2I Oral Prosthetics. PMID- 26995828 TI - FOCUS ON: Regenerative Dentistry. PMID- 26995830 TI - Steal Away. PMID- 26995831 TI - A Q&A With Kevin McKay of DDS Refining. PMID- 26995832 TI - Is Graphene Oxide in Your Future? PMID- 26995833 TI - "Guilty!" Maybe not; Bite-Mark analysis as a Crime-Fighting tool Scrutinized, Deemed Inconclusive. PMID- 26995834 TI - Genetic Cause of Disturbed Dental Development Discovered. PMID- 26995835 TI - Nanofiber Dental Composite Receives FDA Clearance. PMID- 26995836 TI - Promising Gel for Regrowing Enamel. PMID- 26995837 TI - Single-Visit Dentistry Is Here... Are You Ready? PMID- 26995838 TI - CBCT Use in Endodontic Diagnosis. AB - Endodontic diagnosis and treatment planning has taken a giant leap forward due to introduction of CBCT in dentistry. While conventional 2-D radiographs remain the most cost-effective and routine method to evaluate a patient's dentition, their diagnostic potential is limited. The 3-D manipulation of images that CBCT offers provides better insight into diagnostic dilemmas and complicate treatment decisions. Despite the advantages of CBCT imaging, it should be used complimentary to 2-D radiography, not as a replacement. The principle of ALARA (in which patients should be exposed to radiation "as low as reasonably achievable"), still applies to this technology. CBCT should not be used routinely in the absence of clinical signs or symptoms that necessitate a more in-depth view of a tooth and surrounding structures. In other words, if a conventional 2-D radiograph will suffice, then a CBCT pretreatment scan is not necessary. However, if more information is needed to make an accurate diagnosis, a 3-D CBCT image is justified and highly beneficial as shown through several case examples share in this article. PMID- 26995839 TI - Use of Lasers to Treat Failing Dental Implants. PMID- 26995840 TI - Implant Fixture and Abutment Considerations. PMID- 26995841 TI - Removable Prosthetics: Bad Attachments or Bad Design? PMID- 26995842 TI - Simplifying Implant Overdentures: Contemporary Overdenture Abutment and Attachment Systems. PMID- 26995843 TI - A New Restorative Material for Pediatric Dentistry. PMID- 26995844 TI - Creating the "Perfect" Class V Composite: The Matrix Is Key. PMID- 26995845 TI - Interdisciplinary Treatment Planning "What Would You Do If She Were Your Daughter?". PMID- 26995846 TI - Choosing a Durable and Minimally Invasive Alternative: Posterior Partial-Coverage Lithium Disilicate Restorations. PMID- 26995847 TI - Conservatively Recreating a Smile. PMID- 26995849 TI - Oral Health and the Connected Body Symposium--Part 2. PMID- 26995848 TI - A New Approach for Treating Peri-Implantitis: Reversibility of Osseointegration. PMID- 26995850 TI - Relationship between Severity of Aseptic Meningitis and Cerebrospinal Fluid Cytokine Levels. AB - BACKGROUND: Pediatricians sometimes see patients with severe aseptic meningitis and prolonged fever or severe headache, or both. This condition generally has a good prognosis and is usually treated with supportive therapy. However, there is neither guideline nor consensus for the treatment of patients with severe aseptic meningitis. Here, we investigated the relationship between disease severity and biomarkers. METHODS: The subjects were 32 children aged 0 to 14 years, 23 of whom had aseptic meningitis and 9 of whom were meningitis-free controls. Aseptic meningitis was retrospectively categorized into two subgroups, namely mumps meningitis (MM) and viral meningitis excluding that caused by mumps (EM). We defined a novel aseptic meningitis severity score (AMSS) from the signs and symptoms of aseptic meningitis and thus evaluated disease severity. We analyzed the profiles of cytokines in the patients' cerebrospinal fluid (CSF). RESULTS: The AMSS in MM was significantly higher than that in EM. IL-4, IL-6, IL-8, IL-10, and G-CSF levels in MM and EM CSF were higher than those in control CSF. IFN gamma levels were higher in MM than in controls (p<0.01). IL-10 and IFN-gamma levels in MM were higher than those in EM. CONCLUSIONS: MM was more severe than EM. One likely reason is the higher CSF cytokine levels in MM. IFN-gamma may be a potentially strong biomarker of MM severity. Our findings would help further understanding PMID- 26995851 TI - High Prevalence of Non-psychotic Delusions in Children with High-functioning Pervasive Develonmental Disorder. AB - BACKGROUND: Non-psychotic delusions are reported to be associated with depression and anxiety. When these delusions occur in high-functioning pervasive developmental disorder (HFPDD) children, they are often misdiagnosed as schizophrenia and have consequently been studied less. This study has three goals: to investigate the prevalence of non-psychotic delusions in HFPDD children, to test the hypothesis that HFPDD children are more likely to have non psychotic delusions than non-HFPDD children, and to test the hypothesis that non psychotic delusions are associated with depression and anxiety. METHODS: This is a cross-sectional and case-control study. The participants were 45 HFPDD children (cases) and 51 children without HFPDD (controls). Semi-structured interviews were conducted to assess the presence of non-psychotic delusions. We used the Child Behavior Checklist (CBCL) to assess levels of anxiety and depression. RESULTS: Of the cases, 62.2% had non-psychotic delusions, which was significantly higher than controls (25.5%, p<0.001, OR: 4.81, 95% CI: 2.01-11.51). Cases tended to score higher for internalizing problems (including anxiety and depression) on the CBCL than controls (69.8+/-9.4 vs 65.9+/-10.4, t= 1.9, p=0.062). Cases with non psychotic delusions scored significantly higher for internalizing problems in CBCL than children without non-psychotic delusions (72.2+/-7.7 vs 65.7+/-10.7, t=2.4, p= 0.022). CONCLUSIONS: More than half of the HFPDD children were suffering from non-psychotic delusions, and these delusions were associated with anxiety and depression. Therefore, accurate diagnoses of non-psychotic delusions should be conducted for appropriate treatments to be prescribed. PMID- 26995852 TI - Effect of Intratracheal Administration of Adipose-derived Stromal Cells on Bleomycin-induced Lung Injury in a Rat Model. AB - BACKGROUND: Mesenchymal stromal cells (MSCs) have been intensively investigated in regenerative medicine. Among the different types of MSCs, adipose tissue derived stromal cells (ASCs) can be obtained with relatively less invasive techniques. Since ASC administration is a candidate strategy for the treatment of refractory diseases including pulmonary fibrosis, we investigated whether intratracheal injection of ASCs had therapeutic potential against bleomycin (BLM) induced lung injury in rats. METHODS: BLM was intratracheally administered to rats, and 1 week later ASCs were harvested. Two weeks after BLM treatment, ASCs or phosphate-buffered saline (PBS) were injected autologously into the rats via the trachea A semi-quantitative histological evaluation was conducted to assess the injured lungs, followed by cell tracing at 3 or 6 weeks after BLM instillation. RESULTS: ASC administration did not affect the severity of lung damage on the third week after BLM exposure, but prevented further aggravation of the lung injury, as apparent on the sixth week. A fluorescent cell tracer revealed that the majority of ASCs did not appear to have penetrated inside the lung region injured by BLM on the third week after BLM instillation, but some of these cells sprouted deep into the thick distorted architecture of the injured lung on the sixth week after the BLM instillation. CONCLUSIONS: The results of the present study suggest that ASCs may play a role in the prevention of ongoing aggravation of lung injury in the long term. PMID- 26995853 TI - Aggression in Teachers is Related to Role Conflict and Role Ambiguity as Occupational Stress. AB - BACKGROUND: Aggression in the workplace is increasingly recognized as a serious problem, but there are few studies about worker aggression toward outsiders in the workplace. We investigated the association between aggression and occupational stress among teachers. METHODS: This was a cross-sectional study of 1583 teachers, principals, and vice-principals. Aggression was measured using the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ). The survey respondents were classified into tertiles according to the BAQ score. The high BAQ group was defined as the upper tertile for the BAQ total score (BAQ total score 625). Occupational stress was measured using the Japanese version of the Generic Job Stress Questionnaire. Comparisons among the groups were performed using multiple logistic regression analysis. RESULTS: Of the 1583 respondents, 488 were included in the high BAQ group. After adjusting for demographic and occupational variables, high role conflict and role ambiguity were significantly associated with belonging to the high BAQ group. In subscales of the BAQ, high role conflict and role ambiguity related to high levels of hostility, and physical aggression. CONCLUSIONS: Occupational stress such as role conflict and role ambiguity was associated with aggression among teachers. It is necessary to reduce problems which relates to role conflict and role ambiguity for preventing teachers' aggression. PMID- 26995854 TI - The Macroscopic Appearance of Computed Tomography-guided Needle Biopsy Specimens Correlates with Tumor Metastasis in Non-small Cell Lung Cancer. AB - BACKGROUND: Computed tomography (CT)-guided needle biopsy is a well-established and dependable procedure for the diagnosis of pulmonary lesions. Some tissue biopsy samples have loose cohesion and disintegrate into tiny pieces before formalin fixation. The purpose of this study was to assess the association between the fresh macroscopic appearance of samples obtained using CT-guided needle biopsy and the clinicopathological features of non-small cell lung cancer (NSCLC). METHODS: A total of 111 patients who underwent CT-guided lung needle biopsy at Osaka City University Hospital between May 2009 and May 2013 were enrolled. Macroscopic appearance was categorized as either loose or tight cohesion. Samples were evaluated using Azan staining to detect collagen fibers. The staining intensity was multiplied by the percentage of positive cells, and the specimen was categorized as having either low (<100) or high expression ( >=100). Univariate and multivariate logistic regression models were used to evaluate significant covariates for tumor metastasis. RESULTS: In the cohort of 111 patients, the diagnostic rates in loose and tight cohesions were 82.6% and 87.5%, respectively (p=0.509). In 60 patients diagnosed with NSCLC, Azan staining of collagen fibers was positive in 93.5% of the samples with tight cohesion and 28.6% of the samples with loose cohesion (p<0.001). In the multivariate logistic regression models, distant metastasis was significantly associated with loose cohesion (p=0.026). CONCLUSIONS: These results suggest that the macroscopic appearance of CT-guided biopsy samples correlates with tumor metastasis in NSCLC. PMID- 26995856 TI - Empowerment over charity: How surgeons turned Armenia's tragedy into opportunity. PMID- 26995855 TI - Aneurysm of Pancreatic Artery in Association with Celiac Axis Stenosis: Report of a Case and Review of the Literatures. AB - A 63-year-old Japanese woman with a history of pemphigus was referred to us for abnormal findings of dynamic abdominal CT where three aneurysms of splenic artery and pancreaticoduodenal artery, celiac axis compression, and gall stone. Superior mesenteric artery supplied hepatic arterial flow via pancreaticoduodenal artery. Avoiding transarterial embolization to prompt arterial ischemia of liver/pancreas head/duodenum, she laparotomically underwent cholecystectomy, splenectomy, transection of median arcurate ligament, and ligation of splenic and inferior pancreaticoduodenal artery all at once. Postoperative course was uneventful except drainage of abdominal abscess, and she remained well without aneurysm recurring 40 months post. Important point of treatment for pancreaticoduodenal artery aneurysm associated with celiac artery occlusion/stenosis is both preventive solutions for rupture of aneurysm and hepatic/duodenal/pancreatic arterial ischemia. Remaining main arterial supply for the liver via pancreaticoduodenal artery from superior mesenteric artery would prompt recurrent aneurysm of pancreaticoduodenal artery. When a clinician encounters a case of pancreatic aneurysm associated with celiac axis occlusion, the case should be treated using with multimodality such as interventional radiology, and vascular surgery. PMID- 26995857 TI - Leading without a title. PMID- 26995858 TI - The view from the Chair of the YFA. PMID- 26995859 TI - The view from the Chair of the RAS-ACS. PMID- 26995861 TI - Dissemination and implementation: Translating cancer guidelines and clinical trial outcomes into everyday practice. PMID- 26995860 TI - Preparing for MACRA implementation. PMID- 26995862 TI - SRGS and the COT trauma education programs: Keeping surgeons current on the provision of optimal patient care. PMID- 26995863 TI - Credentialing and privileging: Five tips for ASCs. PMID- 26995864 TI - NTDB data point: 2015 Pediatric Report: Pediatric regional trauma. PMID- 26995866 TI - Time to change the general surgery MOC exam. PMID- 26995867 TI - Service members injured in combat should not have to seek volunteer care. PMID- 26995865 TI - Apps incorporating clinical photography offer the potential to improve care. PMID- 26995868 TI - ACS and AGS release geriatric perioperative recommendations. PMID- 26995870 TI - [Results of Training for Personnel Involved in Blood-Transfusion Testing Outside of Regular Work Hours at Saga University Hospital]. AB - Laboratory testing prior to blood transfusion outside of regular hours in many hospitals and clinics is frequently conducted by technicians without sufficient experience in such testing work. To obtain consistent test results regardless of the degree of laboratory experience with blood transfusion testing, the number of facilities introducing automated equipment for testing prior to blood transfusion is increasing. Our hospital's blood transfusion department introduced fully automated test equipment in October of 2010 for use when blood transfusions are conducted outside of regular hours. However, excessive dependence on automated testing can lead to an inability to do manual blood typing or cross-match testing when necessitated by breakdowns in the automated test equipment, in the case of abnormal specimen reactions, or other such case. In addition, even outside of normal working hours there are more than a few instances in which transfusion must take place based on urgent communications from clinical staff, with the need for prompt and flexible timing of blood transfusion test and delivery of blood products. To address this situation, in 2010 we began training after-hours laboratory personnel in blood transfusion testing to provide practice using test tubes manually and to achieve greater understanding of blood transfusion test work (especially in cases of critical blood loss). Results of the training and difficulties in its implementation for such after-hours laboratory personnel at our hospital are presented and discussed in this paper. [Original] PMID- 26995869 TI - [Verification and Validation on Single Nucleotide Polymorphism Analysis of Alcohol Metabolism-Related Genes ADH1B and ALDH2, Using Dried-Saliva Samples]. AB - We have developed a new method for unprocessed biological specimens as templates directly into the TaqMan assay. Saliva was needed to be put on a water-soluble paper and dried, because foreign substances, such as a filter paper, hinder fluorescence detection through the assay. Genotyping of alcohol metabolism related genes ADH1B (rs1229984) and ALDH2 (rs671) polymorphisms was, subsequently, performed by TaqMan PCR assay using dried saliva in the present investigation. The optimized technique was tested on 114 samples of alcoholic patients. The PCR-RFLP methods with purified DNA from blood samples were employed for validation of the assay. Upon validation, complete concordance was observed between the two independent results. These results highlight the ability of TaqMan PCR assays using dried saliva on water-soluble paper in genotyping of ADH1B and ALDH2 genes. Our results showed a rapid, simple, reliable, and cost effective method for SNP genotyping of mutations in ADH1B and ALDH2 genes. This will be very useful for large-scale association studies in various fields. [Original]. PMID- 26995871 TI - [A New Method of Analyzing the Closing Volume (CV) Curve: "N2 First Derivative Wave Method"]. AB - Evaluation of the lung function involves the measurement of many factors. The closing volume (CV) curve is clinically important as an index of uneven alveolar ventilation and airway closure. Although conventional methods for CV measurement are usually based on the pattern of the exhaled nitrogen (N2) concentration curve with respect to the lung volume, it is often difficult to measure the steep pattern of patients with chronic obstructive pulmonary disease (COPD). In this paper, we proposed a new method called the "N2 first derivative (fdN) wave method" for measuring CV. The N2 concentration of the CV curve was transformed to a derivative with respect to the lung volume, which revealed the existence of cardiogenic oscillations. Discrimination between phases III and IV was straightforward based on the difference in the slope or in the amplitude of oscillations of the fdN wave. Our new method was able to distinguish phase IV from phase III using the difference in amplitude of the oscillation of the fdN wave even in the presence of COPD with steep patterns of the CV curve. Close relationships were seen among normal subjects including COPD patients in both the slope of the alveolar plateau (DeltaN2) and the CV values measured with the conventional and new methods. In conclusion, the new method we propose in this paper was able to provide measurements of CV for all subjects including those with COPD. [Original] PMID- 26995872 TI - [Abnormal Serum Total Protein Measurement by Lipoprotein-X in an Infant with Biliary Atresia]. AB - Lipoprotein-X (LP-X) in cholestatic jaundice causes abnormal reaction in assays for low-density lipoprotein-cholesterol, but the effects on other test items are unknown. Here, we report an infant with biliary atresia showing abnormal reaction in total serum protein assay using the biuret method, and lipoprotein-X (LP-X) was then detected. In this 11-month-old female infant, jaundice was observed at 2 months old, and a diagnosis of biliary atresia was made. On biochemical tests at 12 months old, the total serum protein concentrations detected by the biuret method were very high, and the response curve and linearity of dilution were abnormal. LP-X was detected by agar electrophoresis. In addition and recovery experiments with normal serum fractionation of the patient's LP-X-rich lipoprotein fraction prepared by ultracentrifugation, normal gamma-globulin fractionation showed an abnormal reaction by the biuret method. In infants with biliary atresia, we showed that the total serum protein assay by the biuret method was influenced by LP-X-rich lipoprotein, which may be caused by abnormal reaction of LP-X and gamma-globulin. [Case Report]. PMID- 26995873 TI - [Nine-Year Experience after ISO 15189 Acquisition, How Successful was It? Focusing on the Results of Interviews and Questionnaires]. AB - Our laboratory, for the purpose of Quality Management System (QMS) improvement, acquired ISO 15189:2003 accreditation 9 years ago and completed the renewal to ISO 15189:2012 last year. In this study, we reviewed the efficacy of ISO 15189 based on an analysis of laboratory director's and managers' opinions. We could realize QMS improvement through the proactive implementation of preventive and corrective actions, and also the continuous implementation of education and delivery by means of reviewing the interview records of ISO 15189:2012 renewal with the laboratory director. All answers to the questionnaire obtained from managers with regard to the advantages of ISO 15189 acquisition agreed with the purpose of ISO 15189. From these results, we concluded that ISO 15189 acquisition was successful for QMS improvement. [Review]. PMID- 26995874 TI - [Mission of Medical Technologists in Emergency Medicine]. AB - A clinical laboratory test is an auxiliary way to facilitate an accurate diagnosis and medical care; therefore, the essence of such clinical tests would not change at all even if laboratory technology and systems are improved. On the top of that, clinical tests have an important responsibility in medical treatment. Especially, a clinical test in emergency medicine or a life threatening situation is more important to save lives. The responsibility and importance of clinical laboratory tests in patient care are increasing due to the high capability for not only diagnosis but also making critical medical decisions and judging the level of seriousness, emergency, and efficacy of the medical treatment prescribed. Recently, medical treatment became advanced and complicated, meaning that emergency laboratory tests should be prioritized based on the seriousness and critical condition of patients. We, medical technologists, need to work more aggressively and understand the situation. In this report, I would like to share an opportunity with you to comprehend where we are today with rapid improvements in emergency medicine and the latest systems, and to reconsider how we (medical technologists) are responsible for contributing to better patient care. [Review]. PMID- 26995875 TI - [Measures to Ensure Ongoing Medical Laboratory Support of the Emergency Department]. AB - Following the accreditation of this hospital as an Emergency and Critical Care Center and the subsequent establishment of an emergency intensive care unit in April 2013, walk-in patients of the Emergency Department now total over 60,000 annually, with 10,000 arriving by ambulance. Out-of-hours medical laboratory services in this hospital commenced in 1972, providing services including blood analysis and blood product provision. Since the establishment of the Emergency and Critical Care Center, an increase in the number of severe cases has also led to an increase in blood transfusions, requiring a specialized response from the Medical Laboratory. We describe measures taken by the Medical Laboratory to continue ongoing laboratory support of the Emergency Department. [Review]. PMID- 26995876 TI - [The First Step Aiming at the Prevention of Hypertension and Atherosclerosis. Identification of Individuals at High Risk of Hypertension]. AB - Hypertension is an established risk factor of cardiovascular morbidity and mortality. Although antihypertensive treatment reduces the risk of cardiovascular disease, it is impossible to identify all hypertensive subjects among the general population and to manage them in medical facilities considering the huge number of people with hypertension. Furthermore, more than half of cardiovascular events occur in individuals with mild hypertension or in those with a lower blood pressure. In this context, primary prevention of hypertension is an important public health problem. We investigated predictive values of several possible risk factors of hypertension in a general normotensive population. Normotensive subjects who visited our hospital for a physical checkup were enrolled and followed up for 4-5 years, with the endpoint being the development of hypertension. Each factor of metabolic syndrome was closely associated with the future onset of hypertension in subjects without hypertension, and the risk of hypertension markedly increased with overlapping metabolic disorders in individuals. Similarly, serum uric acid, the glomerular filtration rate, urinary albumin (even within the normal range), and brachial-ankle pulse wave velocity were independent risk factors of hypertension. These factors were also independent determinants of a future increase in the systolic blood pressure. An intensive targeted strategy focused on identified individuals at highest risk of developing hypertension is an attractive approach for the primary prevention of hypertension. [Review]. PMID- 26995877 TI - [Companion Diagnostics for Solid Tumors]. AB - Companion diagnostics (CoDx) will likely continue to rapidly increase in number and application to disease areas including solid tumors, for example EGFR for gefitinib and ALK fusion gene for crizotinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; HER2 for trastuzumab in breast cancer. CoDx are an indispensable part of personalized medicine and pharmacogenomics. In CoDx development, there are still many challenges, such as the business model promoting cooperation between diagnostics and pharmaceutical companies, and also the regulations related to CoDx. The FDA notice on the development of CoDx in 2011 recommended the co-development of a new drug and CoDx as the best practice, and the Ministry of Health, Labour and Welfare in Japan also issued a statement in 2013. In addition, the recent discovery of many novel variants in the DNA sequence, advances in sequencing and genomic technology, and improved analytic methods have enabled the impact of germline and somatic mutations to be determined using multiplex diagnosis. The complex challenges to develop CoDx necessitate a close collaboration among academic institutions, regulatory authorities, and pharmaceutical companies. [Review]. PMID- 26995879 TI - [Companion Diagnostics for Selecting Antiretroviral Drugs against HIV-1]. AB - Currently, the treatment of human immunodeficiency virus involves combination therapy, as antiretroviral therapy(ART). The treatment has improved steadily since the advent of potent combination therapy in 1996. New drugs that offer new mechanisms of action, improvements in potency and activity even against multidrug resistant viruses, dosing convenience, and tolerability have been approved. Among ART with useful drugs, there are two important examinations before starting the treatment using the two kinds of drug. CCR5 co-receptor antagonists, maraviroc, prevent HIV entry into target cells by binding to CCR5 receptors. Genotypic assays have been developed that can determine or predict the co-receptor tropism(i.e., CCR5, CXCR4, or both) of the patient's dominant virus population. The assay for HIV-1 co-receptor usage should be performed whenever the use of a CCR5 antagonist is being considered. One of the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), abacavir, is an important agent to develop recommended regimens for antiretroviral therapy. Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir-containing products, ZIAGEN, Epzicom, and Triumeq. Patients who carry the HLA-B*5701 allele are at high-risk of a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, performing a screening test for the HLA-B*5701 allele is recommended. [Review]. PMID- 26995878 TI - [Companion Diagnostics for Thrombotic Disease]. AB - In recent years, thrombotic disease, including myocardial infarction and ischemic stroke, has rapidly increased in Japan. To treat and prevent thromboembolism, warfarin has been commonly prescribed for a long period as an oral anticoagulant. However, it is difficult to define an appropriate warfarin dose because of large inter-individual variability in dose requirements and the narrow therapeutic range. Recent pharmacogenomic (PGx) studies have shown that several single nucleotide polymorphisms (SNPs) in CYP2C9 (warfarin metabolic enzyme) and VKORC1 (warfarin target enzyme) are responsible for an individual's warfarin sensitivity. In order to realize personalized warfarin treatment, algorithms to estimate the required warfarin dose based on PGx are under consideration, including the cost-effectiveness. Recently, novel oral anticoagulants (NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban) have become available as well as alternatives to warfarin treatment for the prevention of ischemic stroke in non valvular atrial fibrillation. Although NOACs are prescribed at a fixed-dose without frequent monitoring of blood coagulability, it has been reported that there is inter-individual variability in the blood concentration of dabigatran caused by gene polymorphisms. Further studies are needed to perform more effective and safer anticoagulant therapy using NOACs. Progress in PGx studies and the realization of personalized anticoagulant therapy are expected in the future. [Review]. PMID- 26995880 TI - [Optimal Treatment for Rheumatoid Arthritis with Companion Diagnostics]. AB - The medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introduction of biologics in addition to methotrexate, an anchor drug, has made it possible to not only suppress pain and inflammation (clinical remission), but also inhibit joint destruction (structural remission), leading to cure from the disease. Since the condition and pathology are heterogeneous among individual patients, optimal treatment for each patient based on the use of companion diagnostics is desired (precision medicine). ACPA is important to diagnose RA, but also to assess the prognosis. ACPA is also a part of companion diagnostics for preclinical RA because it has been found to be positive before the onset. Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics, have been reported as companion diagnostics for optimal treatment of RA. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of ACPA, and then secondary stimuli to joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. It is possible to cure RA, achieving complete remission, by early aggressive treatment and returning to the pre-clinical state with environmental improvement. [Review] PMID- 26995881 TI - Insulin Resistance and beta-cell Function Calculated by Homeostasis Model Assessment in Lean, Overweight, and Obese Women with Polycystic Ovary Syndrome. AB - OBJECTIVE: To evaluate the homeostasis model assessment (HOMA) measurement of insulin resistance (IR) and pancreatic beta-cell function (%beta) and compare those values between groups of healthy-weight, over-weight, and obese women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Retrospective cohort study of women aged 24-48 with PCOS, diagnosed according to 2004 Rotterdam criteria. Participants were grouped by BMI. Quantitative variables were compared by one-way ANOVA and the Tukey method. Analysis for power to detect a difference between means was conducted. Pearson correlation was used to test differences in frequency distribution. RESULTS: By BMI category, 29 participants were of healthy weight, 11 were overweight, and 11 were obese. HOMA-IR was significantly higher in obese women as compared to overweight and healthy-weight patients (2.88 +/- 2.09, 1.13 +/- 0.73, 0.84 +/- 0.49, respectively; p <0.0001). Moreover, HOMA %beta was significantly increased in obese women as compared to overweight and healthy-weight patients (186.89 +/- 131.62, 106.83 +/- 46.77, 86.60 +/- 40.91, respectively; p<0.0001). Adequate statistical power was not present to distinguish a difference between overweight and normal-weight participants. A positive linear correlation was found between log HOMA-IR and BMI, and between log HOMA-%beta and BMI. CONCLUSION: Obese PCOS patients have a higher risk of elevated insulin resistance and beta-cell function than do those with BMI <30. PMID- 26995882 TI - High Peak Estradiol/Mature Oocyte Ratio Predicts Lower Clinical Pregnancy, Ongoing Pregnancy, and Live Birth Rates in GnRH Antagonist Intracytoplasmic Sperm Injection Cycles. AB - OBJECTIVE: To define the relationship between peak estradiol (E2)/mature oocyte ratio and pregnancy outcomes in gonadotropin-releasing hormone (GnRH) antagonist intracytoplasmic sperm injection (ICSI) cycles. STUDY DESIGN: Retrospective cohort study in the setting of an academic reproductive medicine practice. Records from 162 fresh, autologous, GnRH antagonist ICSI cycles performed between 2009 and 2012 .were analyzed. The main outcome measures were rates of clinical pregnancy (CPR), ongoing pregnancy (OPR), and live birth (LBR). RESULTS: For the primary analysis, 4 groups were created based on peak E2/mature oocyte ratio (group 1: <200, group 2: 200-300, group 3: 300-400, and group 4: >400 pg/mL/oocyte). After adjusting for age, basal FSH, and the number of mature oocytes, a significantly lower OPR was seen in group 4 as compared to group I (OR 0.15, 95% CI 0.03-0.86; p=0.032) and group 3 (OR 0.17, 95% CI 0.03-0.98; p=0.048), respectively. The adjusted LBR was also significantly lower in group 4 as compared to group 1 (OR 0.15, 95% CI 0.03-0.83; p=0.030). In a secondary analysis, 3 ranges of peak E2/ mature oocyte ratio (<200, 200-400, and >400 pg/ mL/oocyte) were compared between low, normal, and high responders (<6, 6-15, and >15 mature oocytes, respectively). Clinical pregnancy rate, OPR, and LBR were all lower in normal responders when the E2/oocyte ratio exceeded 400 pg/mL/oocyte as compared to <200 pg/mL/oocyte and 200-300 pg/mL/oocyte (CPR 1% vs. 16% and 32%, respectively, p=0.017; OPR 0 vs. 15% and 27%, respectively, p=0.011; and LBR 0 vs. 13% and 26%, respectively, p=0.018). CONCLUSION: Very elevated peak E2/mature oocyte ratio is associated with a lower CPR, OPR, and LBR in fresh, autologous, GnRH antagonist ICSI cycles. PMID- 26995883 TI - Intraoperative Ureteral Kinking During Uterosacral Ligament Suspension: Effect of Training Level on Occurrence. AB - OBJECTIVE: To determine the rate of ureteral kinking during uterosacral ligament suspension (USLS) procedures at a tertiary referral center and to describe the effect of surgical training level on this occurrence. The secondary aim is to determine the mean additional anesthesia time associated with management of this complication. STUDY DESIGN: This retrospective cohort study included all USLS procedures at our tertiary referral center from June 2011 to December 2013. Cases of USLS with ureteral kinking were compared to uncomplicated cases to determine the impact of surgeon training level on this occurrence. RESULTS: A total of 161 USLS procedures were performed during the study period; 10 had ureteral kinking (6.2%). Level of surgeon training significantly impacted ureteral kinking, with higher rates of kinking occurring among surgeons in earlier training. The occurrence of ureteral kinking during USLS significantly increased the procedure. time by a mean of 86 minutes when the surgery included vaginal hysterectomy and anterior/ posterior colporrhaphy (266.5+/-34.6 min vs. 180.1 +/-43.0 min, respectively; p=0.0078). CONCLUSION: Ureteral kinking occurred in 6.2% of USLS procedures at a tertiary referral center and is associated with a learning curve with statistically significant higher kinking rates among less experienced surgeons. Novel teaching methods should be considered to reduce the learning curve for this procedure. PMID- 26995884 TI - Diversity of Physician Faculty in Obstetrics and Gynecology. AB - OBJECTIVE: To investigate physician faculty diversity in obstetrics and gynecology (ob-gyn) and how it compares with other clinical departments and medical student demographics. STUDY DESIGN: Data from the Association of American Medical College's Faculty Roster were extracted to differentiate full-time physician faculty by gender and by underrepresentation in medicine (Black, Hispanic, Native American/ Alaskans, and Pacific Islanders). Whole population data were updated on a rolling basis from the earliest year of reliable data (1973) to the most recent year (2012). RESULTS: The total number of full-time ob gyn faculty increased from 922 in 1973 to 4,208 in 2012. The increase in proportion of faculty who were women (from 9.9% to 52.7%) contributed to the growth of underrepresented faculty (from 7.7% to 13.3%) during this period. Percentages of ob-gyn faculty who were women and underrepresented in 2012 were higher than in other core clinical departments and similar to those of current medical student matriculants. CONCLUSION: Expansion of physician faculty in ob gyn over the past 40 years has led to greater diversity than exists in many other departments and is more reflective of medical student demographics. PMID- 26995885 TI - Thyroid Disorders in Young Females with Polycystic Ovary Syndrome and Correlation of Thyroid Volume with Certain Hormonal Parameters. AB - OBJECTIVE: To investigate the prevalance of hypothyroidism, thyroid autoimmunity, and ultrasonographic features in polycystic ovary syndrome (PCOS) patients and compare them with a control group, and to detect correlation of thyroid volume [TV] with luteinizing hormone (LH), insulin-like growth factor binding protein-3 (IGFBP-3), and IGF-1 in patients with PCOS. STUDY DESIGN: Seventy PCOS patients' and 84 age-matched controls were enrolled. The patient and control groups were compared according to hormonal parameters, anthropometric measures, TV, echogenicity on ultrasonogram, and autoimmunity. We also investigated the correlation between TV and homeostasis model assessment (HOMA), serum LH, IGF-1 and IGFBP-3 levels in the PCOS group. RESULTS: Body mass index (BMI), Ferriman Gallwey score, fasting insulin level, DHEAS, total and free testosterone, LH, TV, and IGFBP-3 levels were significantly higher in PCOS patients as compared to control group. TV was similar in patients with or without insulin resistance diagnosed with HOMA-estimated insulin resistance (IR). There was no difference in prevalence of hypothyroidism or ultrasonographic features in the groups. We have detected a positive and significant correlation between TV and BMI. We have found that there was no meaningful correlation between the TV and serum IGF-1 levels, whereas TV was positively correlated with serum LH. CONCLUSION: We could not find any correlation between TV and IGF-1, but the most likely etiology of the increased TV in PCOS appears to be related to elevated LH levels in those patients. PMID- 26995886 TI - ACOG Scientific Integrity Deficiency in Recommendation for the Practice of Cosmetic-Plastic Gynecology Misleads Other Gynecological Societies, Inhibits Clinical Education and Research, and Jeopardizes Women's Health. AB - OBJECTIVE: To analyze scientific integrity (scientific quality, objectivity, credibility, and appropriate transparency) of recommendations of gynecologic societies for female genital cosmetic surgery (FGCS) and their references, which were used to support these recommendations. STUDY DESIGN: The scientific integrity of recommendations for FGCS published by gynecologic societies has never been subjected to scientific scrutiny. Electronic and manual searches for FGCS literature published in the English language were conducted and analyzed for the period of the recommendations. A methodological scientific review of recommendations of gynecologic societies for FGCS was performed. The scientific quality, objectivity, credibility, and appropriate transparency within recommendations of gynecologic societies for FGCS were evaluated. RESULTS: Overt prejudice and residual bias were found in the recommendations of gynecologic societies relating to FGCS. Scientific imprecise interpretations and omissions of references called current recommendations into questions. CONCLUSION: Recommendations issued by gynecologic societies relating to FGCS did not meet the scientific integrity norms for scientific quality, objectivity, credibility, and appropriate transparency. PMID- 26995887 TI - Expression of Heme Oxygenase-1 and Leukemia Inhibitory Factor in Maternal Plasma and Placental Tissue in a Lipopolysaccharide-Induced Late Pregnancy Preterm Birth Mouse Model. AB - OBJECTIVE: To investigate the expression of heme oxygenase-1 (HO-1) and leukemia inhibitory factor (LIF) in maternal plasma and placental tissue in intrauterine infection-induced preterm birth. STUDY DESIGN: Using a mouse model of intrauterine infection in preterm birth, we used magnetic beads to extract normal pregnant mouse spleen Treg cells, injecting them into lipopolysaccharide (LPS) treated pregnant mice. The subjects were divided into 4 groups: control group, LPS group, LPS+PBS group, and LPS+Treg group. RT-PCR and Western blot were used to evaluate HO-1, LIF mRNA, and protein levels in the placenta. ELISA was used to detect these parameters in the peripheral blood of pregnant mice. RESULTS: The expression of HO-1 and LIF in the placenta of the LPS group was significantly decreased when compared to that of the control group (p<0.05). Serum HO-1 and LIF levels were higher than in the control group (p<0.05). In the Treg cell-treated group placental tissue HO-1 and LIF expression were significantly higher than in the LPS group (p<0.05), and serum HO-1 and LIF expression were significantly lower than in the LPS group (p<0.05). CONCLUSION: HO-1 and LIF participate with Treg cells in the maternal-fetal interface, producing a unique immune microenvironment. PMID- 26995888 TI - Role of Genistein in Preeclampsia: A Case-Control Study. AB - OBJECTIVE: To examine the association between genistein intake (estimated from a food frequency questionnaire [FFQ) and incidence of preeclampsia. STUDY DESIGN: The study was conducted at University Malaya Medical Center, Kuala Lumpur, and involved 32 women with preeclampsia and 32 healthy pregnant women (matched by parity and gestational age). A validated FFQ was used to collect information regarding dietary intake of genistein during their pregnancy. The association between preeclampsia and the level of genistein intake was evaluated by categorizing the participants into 3 groups according to tertiles of estimated genistein intake. RESULTS: The odds ratio estimates showed a four-fold increase in the risk of developing preeclampsia for tertile 1 (lowest intake) as compared with tertile 3 (highest intake) (crude OR, 4.38; 95% CI 1.21-15.81). CONCLUSION: Lower levels of genistein intake were associated with an increased risk of developing preeclampsia. These findings suggest a possible beneficial role of genistein in the prevention of preeclampsia. PMID- 26995889 TI - Fibroids During Pregnancy: Effects on Pregnancy and Neonatal Outcomes. AB - OBJECTIVE: To determine the effects of fibroids on pregnancy and neonatal parameters. STUDY DESIGN: A total of 12,855 consecutive pregnant women admitted to a tertiary care university hospital between January 2002 and December 2009 were retrospectively reviewed. Of those, 267 patients with fibroids and 267 age- and parity-matched controls were included. The Clavien-Dindo classification was used to grade postoperative complications. RESULTS: Mean gestational age at delivery (p<0.001) and mean neonatal birthweight (p=0.034) were significantly different between the 2 groups. We recorded a higher rate of pain-related hospitalization in the large fibroid group (38.2% and 7.8%, p <0.001). Myomectomy was performed in 124 of 267 patients during cesarean section (C/S). The myomectomy group was associated with lower postoperative hemoglobin levels (p=0.01) and higher need for transfusion (p=0.009). When postpartum hemoglobin levels of the control group and fibroid group without myomectomy were compared, hemoglobin levels were higher in favor of the control group (p = 0.009). CONCLUSION: Beyond lower gestational age and mean birthweight, perinatal complications did not increase with fibroids during pregnancy. Performing myomectomy increases the need for transfusion (Grade 2) without an increase in the risk of hysterectomy (Grade 3) and other life-threatening complications (Grade 4-5). Leaving fibroids in situ during C/S did not prevent a fall in post partum hemoglobin levels. PMID- 26995890 TI - Primary Ovarian Ectopic Pregnancy: Still a Medical Challenge. AB - OBJECTIVE: To investigate the clinical presentation of women with primary ovarian pregnancy diagnosed in recent years and to compare it to tubal pregnancy. STUDY DESIGN: Seven women treated for primary ovarian pregnancy from 2002-2013 were retrospectively identified and compared to 42 women with tubal pregnancies (involving either tubal rupture or tubal abortion) operated on during the same period. In the ovarian pregnancy group the pathology examination confirmed primary ovarian pregnancy according to the Spiegelberg criteria. RESULTS: Seven women underwent surgery for primary ovarian pregnancy during the study period. Five women presented with hemodynamic shock. A ruptured ovarian pregnancy was identified in all cases. Wedge resection was performed by laparotomy in 1 case and by laparoscopy in 6 cases. The mean estimated blood loss was significantly higher in those women with ovarian versus tubal pregnancy (1057.1 +/- 472.1 mL vs. 250.2 +/- 241.5 mL, respectively, p<0.001). Moreover, a statistically significant difference was found when we compared postoperative hospitalization days (2 +/- 0.6 vs. 1.3 +/- 0.7, respectively; p=0.01) in the ovarian pregnancy group as compared with the tubal pregnancy group. CONCLUSION: Primary ovarian ectopic pregnancy is still a major challenge for early diagnosis and treatment; it is associated with rupture and massive intraabdominal bleeding. PMID- 26995891 TI - Changes in Insurance Status in CHOICE Project Participants. AB - OBJECTIVE: To evaluate changes in insurance status of the Contraceptive CHOICE Project (CHOICE) participants between enrollment and long-term (5-year) follow up. STUDY DESIGN: A random sample of 463 CHOICE participants who received an intrauterine device between January 2008 and June 2009 were contacted for a follow-up telephone survey (median follow-up time, 69.6 months). This sub-study compares the insurance statuses at enrollment and at follow-up using a related samples McNemar test. RESULTS: This analysis includes the 311 women who consented to participate in the follow-up survey and provided insurance status information. These women had a mean age of 34 years, 51% were white, and 19% had a household income below 100% of the federal poverty level. We noted a statistically significant change in insurance status over this time period (41% uninsured at time of enrollment, 24% uninsured at time of follow-up; p<0.001). Multinomial analysis showed that a change to full-time employment was associated with gaining insurance (RR= 1.97, 95% CI 1.12-3.47). CONCLUSION: Women in this study were more likely to gain insurance than lose insurance between enrollment in CHOICE and at the time of follow-up. Since insurance status is associated with positive health outcomes, this improvement in insurance status is promising. PMID- 26995892 TI - Retained Products of Conception Associated with Intravasation of Hysterosalpingogram Contrast and Hysteroscopic Distention Media: A Case Report. AB - BACKGROUND: Hysteroscopic resection of retained products of conception has not been previously described to increase the risk for volume overload at the time of hysteroscopy. CASE: A 35-year-old woman with a history of recurrent pregnancy loss was evaluated by a hysterosalpingogram that identified retained products of conception with adjacent contrast intravasation. She underwent a hysteroscopic resection of the uterine septum and products of conception. During the 15 minute operating time she developed a fluid deficit of 2,300 cc of 3% sorbitol with resulting hyponatremia despite normal pressure and flow settings on the fluid management equipment. CONCLUSION: When a hysterosalpingogram demonstrates likely retained products of conception with an accompanying intravasation of contrast media, the provider should consider this finding a potential risk factor for excess intravasation of hysteroscopic distention media and take additional precautions to avoid volume overload. PMID- 26995893 TI - Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report. AB - BACKGROUND: Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. CASE: An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. CONCLUSION: Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure. PMID- 26995894 TI - Effect of Growth Hormone on Endometrial Thickness and Fertility Outcome in the Treatment of Women with Panhypopituitarism: A Case Report. AB - BACKGROUND: The role of growth hormone (GH) in female reproduction has become a topic of increasing interest over the last decade. The replacement of GH for ovulation induction in women with hypopituitarism remains controversial. The role of GH in the human endometrium is still largely unknown. To the best of our knowledge, this study represents the first case report showing evidence that GH might play a role not only for ovulation induction, but also for the development of endometrial thickness in women with hypopituitarism. CASE: A 32-year-old hypophysectomized. woman, known for primary infertility, experienced multiple IVF/embryo transfer failures with inadequate endometrial development. The use of GH replacement therapy followed by conventional controlled ovarian hyperstimulation enabled endometrial development and better ovarian response to gonadotropins, leading to a successful ongoing pregnancy. CONCLUSION: The substitution with GH resulted in fewer days of ovarian stimulation, an acceptable endometrium, and a twin pregnancy delivered at 38 weeks' gestation. PMID- 26995895 TI - Adult Respiratory Distress Disorder Due to Legionnaires Disease in Pregnancy: A Case Report. AB - BACKGROUND: Pneumonia caused by the atypical pathogen Legionella pneumophila during pregnancy is a rare occurrence that carries substantial maternal and fetal risk. CASE: A 36-year-old woman, G3P2002, presented at 33(2/7) weeks' gestation with 6 days of worsening cough, fever, and shortness of breath. She was admitted to the intensive care unit and suffered acute respiratory failure requiring mechanical ventilation. Aggressive diagnostic efforts showed sero- positivity for Legionella IgM. The patient recovered following antibiotic therapy and cesarean delivery. CONCLUSION: Successful treatment of Legionnaires disease requires a high degree of clinical suspicion and prompt empirical treatment when severe community-acquired pneumonia is encountered. In severe cases that are refractory to antimicrobial treatment, cesarean delivery may help resolve compromised maternal respiratory status. PMID- 26995896 TI - Colouterine Fistula Masquerading as a Complex Adnexal Mass: A Case Report. AB - BACKGROUND: Colouterine fistula is one of the rarest complications of diverticulitis, with 23 cases reported in the world literature to our knowledge. Because of its infrequent presentation, there are no standardized diagnostic modalities for this disease, but almost all patients will require surgical treatment. CASE: An afebrile, 66-year-old woman with known diverticulitis presented with vaginal bleeding and discharge of 1 day's duration. Based on imaging she was believed to have a complex adnexal mass. However, it was proven intraoperatively to be a colouterine fistula. CONCLUSION: Although extremely uncommon, the diagnosis of a colouterine fistula can be made with pelvic examination, diagnostic imaging, or surgical exploration. The surgical treatment of colouterine fistulae varies on the acuity of the patient's diverticular disease and the surgeon's suspicion of malignancy. PMID- 26995897 TI - [Seasonal release characteristics of Ca, Mg and Mn of foliar litter of six tree species in subtropical evergreen broadleaved forest]. AB - Seasonal release dynamics of Ca, Mg and Mn during decomposition of foliar litter of Pinus massoniana, Cryptomeria fortunei, Cunninghamia lanceolata, Cinnamomum camphora, Toona ciliate, and Quercus acutissima were investigated in subtropical evergreen broad-leaved forest employing the method of litterbag. After one-year decomposition, the release rates of Ca, Mg and Mn in foliar litter of the studied tree species ranged from -13.8% to 92.3%, from 4.0% to 64.8%, and from 41.6% to 81.1%, respectively. Ca dynamics in foliar litter of P. massoniana, C. camphora exhibited the pattern of accumulating early and releasing later, while that of the other four tree species showed direct release. Similarly, the dynamics of Mg released from foliar litter of C. camphora showed the pattern of accumulating early and then releasing, while that of the other five tree species exhibited continuous release. Meanwhile, the dynamics of Mn released from foliar litter of C. fortunei and T. ciliate exhibited early accumulation, and subsequent release, while that of the other four tree species showed continuous release. The releases of Ca, Mg and Mn in foliar litter were greatly influenced by seasonal rainfall, and varied with tree species. Furthermore, the rates and amounts of Ca, Mg and Mn released from foliar litter were higher in rainy season than in dry season. In conclusion, the initial nutrient concentrations and precipitation were two key factors influencing the release dynamics of Ca, Mg and Mn during decomposition of foliar litter in the subtropical evergreen broad-leaved forest. PMID- 26995898 TI - [Decomposition and nutrient release of root with different diameters of three subalpine dominant trees in western area of Sichuan Province, China]. AB - In this study, a buried bag experiment was used to investigate mass loss and C, N and P release patterns of fine (<=2 mm), medium (2-5 mm) and coarse (>= 5 mm) roots of 3 subalpine dominant trees, i. e., Betula albosinensis, Abies faxoniana and Picea asperata in the growing and non-growing seasons. In general, the remaining mass of B. albosinensis was lower than that of A. faxoniana and P. asperata. In addition, root remaining mass increased with the increase of root diameter for the same species. The mass losing rate in the non-growing season was 52.1%-64.4% of a year. The C release of B. albosinensis was the highest, but that of A. faxoniana was the lowest. Also, C release decreased with the increase of root diameter. N of A. faxoniana and P. asperata were enriched in the non-growing season but released in the growing season. However, the opposite pattern was found for B. albosinensis. During the non-growing season, the amount of N enrichment increased with the increase of root diameter. The P release of 3 species was characterized as the enrichment-release pattern. P enrichment of A. faxoniana was significantly greater than that of P. asperata and B. albosinensis. Nevertheless, no significant difference was observed between diameter sizes. In conclusion, diameter size had significant effect on root decomposition in the subalpine forests of western Sichuan, and the diameter effect was dependent on tree species and season. PMID- 26995899 TI - [Spatial distribution pattern of main populations and gap makers in Picea koraiensis and Abies nephrolepis forest of Xiaoxing' an Mountains, Northeast China]. AB - Species composition and diameter class structure were investigated in 1.5 hm2 (100 m x 150 n) permanent plot in Picea koraiensis and Abies nephrolepis forest of Xiaoxing' an Mountains. The spatial distribution pattern and spatial association of main populations and gap makers were analyzed by using point pattern analysis. The results showed that there were a total of 13 species with diameters at breast height greater than 2 cm in tree layer, and great differences were observed in the densities of main populations. The importance values of A. nephrolepis, P. koraiensis, Betula platyphylla and Acer ukurunduense were ranked in the first 4 in the plot. The diameter class structure of their populations presented an inverse 'J' curve. The spatial distribution patterns for A. nephrolepis and P. koraiensis were similar, which changed from aggregated, random to uniform distribution with the spatial scale. For B. platyphylla, the distribution was aggregated at <=40 m scale, and random at >40 m scale, whereas A. ukurunduense presented an aggregated distribution pattern at the whole research scale. Except that the negative correlation between B. platyphylla and A. ukurunduense existed at the whole research scale, positive correlation between the other populations at small scale and negative correlation at large scale were observed. Only A. nephrolepis and B. platyphylla had significant positive correlation, and generally no significant correlation existed between other populations. Spatial distribution pattern of gap makers was characterized as aggregated distribution at small and middle scales, and random distribution with increasing scale. Spatial point pattern of gap makers formed by uprooting exhibited unimodal type distribution, and random, aggregated, and uniform distribution also occurred. Spatial point pattern of gap makers formed by breaking overall presented a little fluctuation, random and aggregated distributions alternatively appeared at small scale, and random distribution happened at large scale. Their spatial correlation analysis indicated that significant positive correlation existed at <=32 m scale, and non-significant negative correlation at >32 m scale. PMID- 26995900 TI - [Dynamic changes in soil respiration components and their regulating factors in the Moso bamboo plantation in subtropical China]. AB - Dynamic changes (from April 2013 to March 2014) in soil respiration components were investigated by Li-8100 in the Moso bamboo plantation in Lin' an City, Zhejiang Province. Results showed that the average annual values for the soil total respiration rate, heterotrophic respiration rate, and autotrophic respiration rate in the Moso bamboo plantation were 2.93, 1.92 and 1.01 imol CO2 . m-2 . s-1, respectively. The soil respiration rate and its components exhibited strongly a seasonal dynamic pattern. The maximum appeared in July 2013, and the minimum appeared in January 2014. The annual cumulative CO2 emissions through soil respiration, heterotrophic respiration, and autotrophic respiration were 37.25, 24.61 and 12.64 t CO2 . hm-2 . a-1, respectively. The soil respiration and its components showed a close relation with soil temperature of 5 cm depth, and the corresponding Q10, values at 5 cm depth were 2.05, 1.95 and 2.34, respectively. Both the soil respiration and heterotrophic respiration were correlated to soil water soluble organic C (WSOC) content, but no significant relationship between autotrophic respiration and WSOC was observed. There were no significant relationships between soil respiration components and soil moisture content or microbial biomass C. The seasonal changes in soil respiration components in the Moso bamboo plantation were predominantly controlled by the soil temperature, and the soil WSOC content was an important environmental factor controlling total soil respiration and soil heterotrophic respiration. PMID- 26995901 TI - [Effects of conversion of natural broad-leaved forest to Chinese fir plantation on soil respiration in subtropical China]. AB - Soil CO2 effluxes in natural broad-leaved forest and the conversed Chinese fir plantation in Linglong Mountains Scenic of Zhejiang Province were evaluated by using static closed chamber and gas chromatography method. The results showed that soil CO2 efflux showed consistent seasonal dynamics in natural broad-leaved forest and Chinese fir plantation, with the maximums observed in summer and autumn, the minimums in winter and spring. Soil CO2 effluxes were 20.0-111.3 and 4.1-118.6 mg C . m-2 . h-1 in natural broad-leaved forest and Chinese fir plantation, respectively. The cumulative soil CO2 emission of natural broad leaved forest (16.46 t CO2 . hm-2 . a-1) was significantly higher than that of Chinese fir plantation (11.99 t CO2 . hm-2 . a-1). Soil moisture did not affect soil CO2 efflux. There was a significant relationship between soil CO2 efflux and soil temperature at 5 cm depth. There was no significant relationship between soil CO2 efflux of natural broad-leaved forest and water soluble organic carbon content, while water soluble organic carbon content affected significantly soil CO2 efflux in Chinese fir plantation. Converting the natural broad-leaved forest to Chinese fir plantation reduced soil CO2 efflux significantly but improved the sensitivity of soil respiration to environmental factors. PMID- 26995902 TI - [Spatial distribution pattern and allometric growth of three common species on moving sand dunes in Horqin Sandy Land, China]. AB - Research on fine scale pattern and characteristics of allometric growth could contribute to better understanding plants' adaptation in moving sandy dunes. The abundance, height and biomass of 3 species Agriophilum aquarrosum, Corispermum candelabrum and Setaria viridis in twenty-eight 1 m x 1 m quadrats of Horqin Sandy Land were identified, mapped and described. The nearest neighbor method and O-ring O(r) function analysis were applied to analyze the spatial patterns. The results showed that the individual spatial pattern was mainly aggregated in 1 m x 1 m quadrat at community level but mainly random at population level. At 0-50 cm individual distance scale, both intraspecific and interspecific relationship were facilitation and aggregated distribution occurred at some scales and varied with increasing plant abundance in 1 m x 1 m quadrat. In 0-40 cm, the aggregated distribution of S. viridis and A. aquarrosum increased obviously; in 10-20 cm, both intraspecific and interspecific aggregation increased; in 10-30 cm, the occurrence possibility of positive correlations between S. viridis and A. aquarrosum, S. viridis and C. candelabrum all increased; in 40-50 cm, the possibility of positive correlations between A. squarrosum and S. viridis, A. squarrosum and C. candelabrum all increased. Research on the three species components indicated that the growth rate of above-ground was faster than that of underground. S. viridis had the highest ratio of under-ground biomass to above ground biomass but its nutritional organs' biomass ratio was medium. C. candelabrum allocated more biomass to propagative organs and stem, but A. squarrosum allocated more biomass to nutritional organs. Based on the spatial distribution and allometric characteristics, the three common species in moving sand dunes preferred r strategy in their life history. PMID- 26995903 TI - [Effects of intensive management on abundance and composition of soil N2-fixing bacteria in Phyllostachys heterocycla stands]. AB - Denaturing gradient-gel electrophoresis and real-time quantitative PCR (qPCR) were employed to determine the effects of intensive management on soil N2-fixing bacteria in a moso bamboo (Phyllostachys heterocycla) plantation. Soil samples were collected from the moso bamboo stands receiving 0 (CK), 10, 15, 20, and 25 years of intensive management. It was found that intensive management caused a strong decrease in soil pH but a general increase in soil available nutrients. The structure of the N2-fixing bacterial communities in the soils having received 10 and 25 years of intensive management were quite similar to that from the CK; however, those from 15 and 20 years of intensification differed from the CK. With increasing time of intensive management, the abundance and diversity of the nifH gene at first decreased and then increased, with the minimum values being observed after 15 years of intensive management, indicating the eventual resiliency of N2-fixing bacteria to disturbance induced by intensive management. Redundancy analysis indicated that soil available potassium, available nitrogen, nitrite nitrogen, and ammonium nitrogen were more closely related to the changes of N2-fixing bacterial community structure compared with the other soil indices measured. In conclusion, the soil N2-fixing bacterial community was negatively affected by intensive management in the short term, but could recover in the long term. PMID- 26995904 TI - [Simulation of the branch biomass for Chinese fir plantation using the linear mixed effects model]. AB - Based on data obtained from 572 branches of 45 Chinese fir trees in Jiangle Forest Farm, Fujian Province, southeast China, prediction models for branch, foliage biomass and total branch and foliage biomass of individual tree were developed by linear mixed effects (LME) method, and tested by independent samples. The results showed that the LME models provided better performance than the multiple linear regression models for the branch, foliage and total biomass prediction of Chinese fir plantation. The LME models with different combinations of the random effects parameters had different fitting precisions. The LME models including variance structures could effectively remove the heteroscedasticity in the data and improved the precision. The LME model with the exponential function as the variance structure had better fitting precisions for the total biomass and foliage biomass models, and that with the constant plus power function as the variance structure had better performance for the branch biomass model. Model validation confirmed that the LME models with the random effects and heteroscedasticity structure could significantly improve the precision of prediction, compared to the multiple linear regression models. PMID- 26995905 TI - [Effect of air temperature and rainfall on wetland ecosystem CO2 exchange in China]. AB - Wetland can be a potential efficient sink to reduce global warming due to its higher primary productivity and lower carbon decomposition rate. While there has been a series progress on the influence mechanism of ecosystem CO2 exchange over China' s wetlands, a systematic metaanalysis of data still needs to be improved. We compiled data of ecosystem CO2 exchange of 21 typical wetland vegetation types in China from 29 papers and carried out an integrated analysis of air temperature and precipitation effects on net ecosystem CO2 exchange (NEE), ecosystem respiration (Reco), gross primary productivity (GPP), the response of NEE to PAR, and the response of Reco to temperature. The results showed that there were significant responses (P<0.05) of NEE (R2 = 50%, R2=57%), GPP (R2 = 60%, R2 = 50%) Reco (R2 = 44%, R2=50%) with increasing air temperature and enhanced precipitation on the annual scale. On the growing season scale, air temperature accounted for 50% of the spatial variation of NEE, 36% of GPP and 19% of Reco, respectively. Both NEE (R2 = 33%) and GPP (R2 =25%) were correlated positively with precipitation (P<0.05). However, the relationship between Reco and precipitation was not significant (P>0.05). Across different Chinese wetlands, both precipitation and temperature had no significant effect on apparent quantum yield (alpha) or ecosystem respiration in the daytime (Reco,day, P>0.05). The maximum photosynthesis rate (Amax) was remarkably correlated with precipitation (P <0.01), but not with air temperature. Besides, there was no significant correlation between basal respiration (Rref) and precipitation (P>0.05). Precipitation was negatively correlated with temperature sensitivity of Reco (Q10, P<0.05). Furthermore, temperature accounted for 35% and 46% of the variations in temperature sensitivity of Reco (Q10) and basal respiration (Rref P<0.05), respectively. PMID- 26995906 TI - [Simulation and validation of diffuse radiation in Qianyanzhou area, Jiangxi, China]. AB - Accurate estimation of diffuse radiation is of great significance for evaluating its effect on terrestrial ecosystem carbon exchange. Based on the observed diffuse radiation data in the meteorological observation field in mid-subtropical Qianyanzhou, Jiangxi, China from March 1, 2012 to February 28, 2013, the simulated results of five widely used diffuse radiation decomposition models (Reindl-1, Reindl-2, Reindl-3, Boland, BRL) were validated. The results indicated that, on the 30 min scale, all of the five models could well simulate the diffuse radiation of this area overall. But the effect of models decreased significantly with the rising of clearness index (kt). Especially when kt>0.75, each model was.unable to simulate diffuse radiation in the region. Regarding the simulation of seasonal change of diffuse radiation, the five models could simulate diffuse radiation well in most months. Relative deviation between simulated and observed values of yearly diffuse radiation of five models had a maximum of 7.1% (BRL), a minimum of 0.04% (Reindl-1), and an average of 3.6%. The simulated values of the five models appeared to be overestimated in the summer when radiation was strongest, temperature was highest, and precipitation was relatively low. For example, in July, the diffuse radiation was overestimated by 14.5%-28.2%, 21.2% on average. This was primarily due to the. method of estimating diffuse radiation under the condition of high kt. The uncertainty requires further evaluation in the model application. Considering the results of validation, simulation precision and the accessibility of input variables, the order of the simulation performance of five models was BRL>Reindl-3>Reindl-2>Reindl-1 >Boland. PMID- 26995907 TI - [Differences and sources of CO2 concentration, carbon and oxygen stable isotope composition between inside and outside of a green space system and influencing factors in an urban area]. AB - The off-axis integrated cavity output spectroscopy technique was used to measure air CO2 concentration, stable carbon (delta13C) and oxygen (delta18C) isotope ratios on the Fourth Ring Road (FRR) and in the green space system of Beijing Institute of Landscape Architecture (BILA) in summer and winter seasons. The variations of CO2 concentration, delta13C value, delta18C value and the differences of them between the FRR and the BILA, which were correlated with traffic volume and meteorological factors, were analyzed at half-hour timescale. The results showed that traffic volume on the FRR was large both in summer and winter with obvious morning and evening rush hours, and more than 150 thousands vehicles were observed everyday during the observation periods. Diurnal variation of the CO2 concentration showed a two-peak curve both on the FRR and in the green space system of the BILA. In contrast, diurnal variation of delta13C value was a two-trough curve while diurnal variation of delta18O value was a single-trough curve. The differences of CO2 concentration, delta13C value and delta18O value between the FRR and the green space system of BILA in summer were greater than those in winter. The carbon isotope partitioning results showed that in summer vehicle exhaust contributed 64.9% to total atmospheric CO2 of the FRR during measurement time, while heterotrophic respiration contributed 56.3% to total atmospheric CO2 of the green space system in BILA. However, in winter atmospheric CO2 from both the FRR and green space system mostly came from vehicle exhaust. Stepwise regression analysis indicated that differences of CO2 concentration between the FRR and green space system were significantly related to vehicle volume and solar radiation at half-hour timescale, while solar radiation and relative humidity were the main meteorological factors causing delta13 and delta18O differences between the FRR and green space system. Plants in the green space system strongly assimilated CO2 from fossil fuel burning by photosynthesis to maintain carbon and oxygen balance of urban area in the growing season, which played an important role in improving urban ecological environment. PMID- 26995908 TI - [Compensation effects of regulated deficit irrigation and tillering interference to winter wheat]. AB - Pot experiments were carried out to explore the approach of optimizing crop group performance through restriction of individual growth redundancy and increasing crop yield potential. Two winter wheat varieties of 'Xiaoyan-22' (with moderate tillering ability) and 'Zhengmai-7698' (with strong tillering ability) were chosen to investigate the effects of two irrigation schedules (full irrigation and regulated deficit irrigation) and three kinds of tillering interference (only retaining the main stem and the biggest tiller at jointing stage; removing all nonbearing tillers at heading stage; and without any interference as the control treatment). Thus, we simulated the compensation effects of different water supplies and unpredictable disturbances on the physiology, growth, yield, and water use efficiency of winter wheat. The results showed that there existed growth redundancy for both varieties. Compared with 'Xiaoyan-22', 'Zhengmai-7698' had relatively higher tillering number but weak panicle traits. Regulated deficit irrigation and removing all nonbearing tillers at heading stage could reduce growth redundancy, weaken competitive ability, change source-sink relations, and optimize resources allocation. However, excessive elimination of redundancy (e.g. only retaining the main stem and the biggest tiller at jointing stage) could destroy the inherent root-shoot balance and functional structure of plant and lead to inadequate compensation. In contrast to the control treatment (full irrigation and without any disturbance), the combination of regulated deficit irrigation and removing all nonbearing tillers at heading stage could help crops sufficiently exploit and utilize their own regulation potentials at spatial and temporal scales and finally realize compensation growth. The combination above could increase the water use efficiency by 20.4% - 25.4% without remarkable impact on grain yield, and hence, could be suitable for wheat growth redundancy reduction. PMID- 26995909 TI - [Root morphological characteristics of barley genotype with high phosphorus efficiency under phosphorus stress]. AB - A pot experiment was carried out to test the effects of phosphorus (P) supply levels (25, 50, and 75 mg P2O5 . kg-1) with two P genotype (efficient DH110+ and DH147, inefficient DH49) barleys on root morphology and the relationships between root morphology and P uptake. The results showed that barley biomass and P uptake were significantly reduced by low P stress. Efficient genotype barley biomass and P uptake were 1.24-1.70 and 1.18-1.83 times as much as those of inefficient genotype barley respectively. The total root length, total root surface area, average root diameter, adventitious root length and root surface area, lateral root length and root surface area of P efficient genotype barley were significantly reduced with decreasing the P supply level in soil. The total root length, total root surface area, specific root length, lateral root length and surface area of P efficient genotype barley were 1.46-2.06, 1.12-1.51, 1.35-1.72, 1.69-2.42; and 1.40-1.78 times as much as that of those of P inefficient genotype barley, respectively, while the average root diameter was 70.6% - 90.2% of P inefficient genotype barley. Principal component analysis showed that the average root diameter, specific root surface area and specific root length could be used to distinguish two P genotype barleys. Partial least squares regression analysis showed that the total root length, total root surface area made great contributions to P uptake of barley in soil. The contribution of the adventitious root length and surface area on P uptake of barley decreased significantly and the average root diameter, specific root length, lateral root length and root surface area increased with the decreasing P supply level in soil. P efficient genotype barley adapted to low P stress through maintaining the lateral root growth, increasing the specific root length and root fineness. PMID- 26995910 TI - [An early warning method of cucumber downy mildew in solar greenhouse based on canopy temperature and humidity modeling]. AB - The greenhouse environmental parameters can be used to establish greenhouse nirco climate model, which can combine with disease model for early warning, with aim of ecological controlling diseases to reduce pesticide usage, and protecting greenhouse ecological environment to ensure the agricultural product quality safety. Greenhouse canopy leaf temperature and air relative humidity, models were established using energy balance and moisture balance principle inside the greenhouse. The leaf temperature model considered radiation heat transfer between the greenhouse crops, wall, soil and cover, plus the heat exchange caused by indoor net radiation and crop transpiration. Furthermore, the water dynamic balance in the greenhouse including leaf transpiration, soil evaporation, cover and leaf water vapor condensation, was considered to develop a relative humidity model. The primary infection and latent period warning models for cucumber downy mildew (Pseudoperonospora cubensis) were validated using the results of the leaf temperature and relative humidity model, and then the estimated disease occurrence date of cucumber downy mildew was compared with actual disease occurrence date of field observation. Finally, the results were verified by the measured temperature and humidity data of September and October, 2014. The results showed that the root mean square deviations (RMSDs) of the measured and estimated leaf temperature were 0.016 and 0.024 degrees C, and the RMSDs of the measured and estimated air relative humidity were 0.15% and 0.13%, respectively. Combining the result of estimated temperature and humidity models, a cucumber disease early warning system was established to forecast the date of disease occurrence, which met with the real date. Thus, this work could provide the micro environment data for the early warning system of cucumber diseases in solar greenhouses. PMID- 26995911 TI - [Safe wintering and economic and ecological benefit of winter rapeseed in dry and cold areas of northern China]. AB - The purpose of this study was to realize the security of safe wintering of winter rapeseed in dry and cold regions of northern China. Experiments were conducted with 18 winter rapeseed (Brassica campestris) varieties at 57 sites from 2008 to 2013 to statistically analyze the wintering rate variation of different varieties in dry and cold regions of northern China. The results showed that, the wintering rate varied from 70% to 90% during the study period in different regions, which had no significant difference between different years and varieties, and had high stability and remarkable economic benefit. With Tianshui as a starting point of winter rapeseed planting, the wintering-safe regions included all Gansu Province , the south of Lasa and Linzhi of Xizang, the east of Minhe of Qinghai, up to Urumqi and Baicheng, and the south of Aletai, Tacheng, the east of Kashi of Xinjiang, it also included the regions along Yellow River eastward to Ningxia, the south of Linhe of Inner Mongolia, the north of Shaanxi, the vicinage of Qixian in Shanxi, Daming in Hebei, Tianjin, Beijing, the north of Weifang of Shandong, the south of Huludao of Liaoning and Yanbian of Jilin. Longyou 6, Longyou 7, Longyou 8 and Longyou 9 were the wintering-safe B. rapa varieties. PMID- 26995912 TI - [Evaluation of zinc deficiency tolerance in different kinds of apple rootstocks]. AB - The objective of this study was to screen and evaluate the zinc deficiency tolerance among eight apple rootstocks, i.e., Malus baccata, M. rockii, M. xiaojinensis, M. sikkimensis, M. sieversii, M. robusta, M. hupehensis and Malus 'Flame'. The experiment took these 8 kinds of root-stocks as the research materials to observe and analyze the index of the rootstock's height, dry biomass, root architecture and zinc concentration, and with help of the fuzzy membership function to work out a comprehensive evaluation on their zinc deficiency tolerance. The result showed that several obvious zinc deficiency symptoms were observed in three kinds of rootstocks (M. rockii, M. sikkimensis and M. sieversii), such as dwarfed plant and newborn small leaves, while such symptoms were not obvious in M. xiaojinensis and M. 'Flame'. The plant biomass, height and zinc accumulation of aerial part greatly decreased under zinc deficiency stress, while smaller reduction was observed in M. xiaojinensis than in other rootstocks. M. xiaojinensis and M. baccata had higher zinc concentrations in leaves than others. According to the fuzzy membership function and cluster analysis, the resistance of the eight apple rootstocks to zinc deficiency was ranked: M. xiaojinensis was the highest one; M. 'Flame' was the second; M. baccata, M. sikkimensis, M. robusta and M. hupehensis were rather weaker; M. rockii and M. sieversii demonstrated the highest sensitivity to zinc deficiency. PMID- 26995913 TI - [Effects of sodium naphthalene acetate on growth and physiological characteristics of tomato seedlings under suboptimal temperature and light condition]. AB - Taking tomato 'Zhongza 105' as test material, the influences of sodium naphthalene acetate (SNA) on growth and physiological characteristics of tomato seedlings under suboptimal temperature and light condition were investigated. The results showed that the dry mass, vigorous seedling index, root activity, total nitrogen content, net photosynthesis rate (Pn) of tomato seedlings were significantly decreased by suboptimum temperature and light treatment. In addition, the catalase activity and zeatin riboside (ZR) concentration were also reduced. However, the superoxide dismutase, peroxidase activity and the content of abscisic acid (ABA) were increased. Compared with treatment of the same volume distilled water on tomato seedlings under suboptimum temperature and light condition, the dry mass of whole plant and vigorous seedling index of tomato seedlings were significantly increased by 16.4% and 22.9%, as the total N contents in roots and leaves and Pn were also increased by 8.5%, 28.5%and 37.0%, respectively, with the treatment of root application of 10 mg . L-1 SNA. Besides protective enzyme activity and the root activity were improved, the indole acetic acid (IAA) and ZR concentration of tomato were raised, and ABA concentration was reduced. The results indicated that root application of certain concentration of SNA could promote the growth of tomato seedlings by increasing the tomato root activity, protective enzymes activity, Pn and regulating endogenous hormone concentration under suboptimum temperature and light condition. PMID- 26995914 TI - [Soil dryness characteristics of alfalfa cropland and optimal growth years of alfalfa on the Loess Plateau of central Gansu, China]. AB - This paper investigated soil moisture in alfalfa (Medicago sativa) cropland with different growth years (1, 3, 8, 12 and 14 years) and discussed the optimum growth years of alfalfa on the Loess Plateau of central Gansu. The results showed that the soil moisture along 0-300 cm soil profile of alfalfa croplands with different growth years was obviously lower than that of the local soil stable moisture. The soil water contents in croplands with alfalfa that had grown for 12 and 14 years were only 9.2% and 7.1% of local soil stable moisture, respectively, which were even lower than the lower limit of alfalfa growth. The average soil dryness indexes along 0-300 cm soil profile in 1, 3, 8, 12 and 14 years alfalfa croplands were 125.4%, 30.5%, 18.4%, -34.2% and -83.3% respectively. The results indicated that soil dryness occurred to varying degrees with different growth years except croplands with alfalfa grown for 1 year. With the increase of growth years of alfalfa, the soil dryness intensity increased and the soil dryness rate decreased. According to the soil moisture and alfalfa productivity results in this study, it could be concluded that the optimum growth years of alfalfa are 8 10 years in semiarid areas of the Loess Plateau. PMID- 26995915 TI - [Effect of long-term fertilization on microbial community functional diversity in black soil]. AB - In order to study the effects of long-term different fertilization on microbial community functional diversity in arable black. soil, we examined microbial metabolic activities in two soil la- yers (0-20 cm, 20-40 cm) under four treatments (CK, NPK, M, MNPK) from a 35-year continuous fertilization field at the Ministry of Agriculture Key Field Observation Station of Harbin Black Soil Ecology Environment using Biolog-ECO method. The results showed that: in the 0-20 cm soil layer, combined application of organic and inorganic fertilizer(MNPK) increased the rate of soil microbial carbon source utilization and community metabolism richness, diversity and dominance; In the 20-40 cm layer, these indices of the MNPK treatment was lower than that of the NPK treat- ment; while NPK treatment decreased soil microbial community metabolism evenness in both layers. Six groups of carbon sources used by soil microbes of all the treatments were different between the two soil layers, and the difference was significant among all treatments in each soil layer (P < 0.05) , while the variations among treatments were different in the two soil layers. Canonical correspondence analysis (CCA) showed that soil microbial community metabolic function of all the treatments was different between the two soil layers, and there was difference among all treatments in each soil layer, while the influences of soil nutrients on soil microbial community metabolic function of all treatments were similar in each soil layer. It was concluded that long-term different fertilization affected soil microbial community functional diversity in both tillage soil layer and down soil layers, and chemical fertilization alone had a larger influence on the microbial community functional diversity in the 20-40 cm layer. PMID- 26995916 TI - [Effects of different application rates of calcium cyanamide on soil microbial biomass and enzyme activity in cucumber continuous cropping]. AB - A 2-year field experiment was conducted to study the effects of CaCN2 combined with cucumber straw retention on soil microbial biomass carbon (SMBC) , soil microbial biomass nitrogen (SMBN) and soil enzyme activities under cucumber continuous cropping system. Four treatments were used in this study as follows: CK (null CaCN2), CaCN2-90 (1350 kg CaCN2 . hm-2) CaCN2-60 (900 kg CaCN2 . hm-2), CaCN2-30 (450 kg CaCN2 . hm-2). The results indicated that, compared with the other treatments, CaCN2-90 treatment significantly decreased SMBC in 0-10 cm soil layer at seedling stage, but increased SMBC in 0-20 cm soil layer after early fruit stage. Compared with CK, CaCN2 increased SMBC in 0-20 cm soil layer at late fruit stage, and increased SMBN in 0-10 cm soil layer at mid- and late-fruit stages, however there was no significant trend among CaCN2 treatments in the first year (2012), while in the second year (2013) SMBN increased with the increasing CaCN2 amount after mid-fruit stage. CaCN2 increased straw decaying and nutrients releasing, and also increased soil organic matter. Furthermore, the CaCN2-90 could accelerate straw decomposition. Compared with CK, CaCN2 effectively increased soil urease, catalase and polyphenol oxidase activity. The soil urease activity increased while the polyphenol oxidase activity decreased with the increase of CaCN2, and CaCN2-60 could significantly improve catalase activity. Soil organic matter, urease activity and catalase activity had significant positive correlations with SMBC and SMBN. However, polyphenol oxidase activity was negatively correlated to SMBC and SMBN. Our findings indicated that CaCN2 application at 900 kg . hm-2 combined with cucumber straw retention could effectively improve soil environment, alleviating the soil obstacles under the cucumber continuous cropping system. PMID- 26995917 TI - [Microbial anaerobic dechlorination of polychlorinated biphenyls in paddy soil slurry]. AB - We studied the dechlorination process of Aroclor1260, a high-chlorinated polychlorinated biphenyls (PCBs) mixture in an anaerobic paddy soil slurry, and further analyzed the related microbial community structures. The Aroclor1260 was reduced up to 55.5% in the natural paddy soil slurry in 128 days, and the reduction percentage dropped to 46.9% after incoculating the paddy soil slurry with a PCBs-dechlorination enrichment culture. The dechlorination mainly occurred in congeners of pentachlorobiphenyl, hexachlorobiphenyl, and specially, the heptachlorobiphenyl, with pentachlorobiphenyl accumulated as dechlorination intermediate. Hydrogen gas produced from fermentation of organic matters was maintained at a lower partial pressure due to its consumption during the dechlorination process, so that the methanogens was suppressed as well. The microbial community structure was significantly different between natural and inoculated paddy soils. Introducing the PCBs-dechlorination enrichment culture changed the local microbial community by the competition between the exogenetic dchlorinators and the indigenous bacteria, overall decreasing the dechlorination activity. PMID- 26995919 TI - [Temporal and spatial distribution of rice drought in Southwest China]. AB - Considering the characteristics of rice production and climate conditions in Southwest China, an agricultural drought monitoring model based on wetness index anomaly rate (Mp) by calculating the variation of deviation from average values of relative humid index was established, and was used to analyze the spatial temporal distribution characteristics of the rice drought during the growth season in Southwest China in the past 50 years (1961-2010). The applicability of the Mp model in Southwest China was verified by using this model to monitor the rice drought. The result showed there was a decreasing trend in the frequency of rice drought in term of the decadal variability. The areas with high drought risk mainly concentrated in northwestern and mid-eastern Yunnan Province, eastern Sichuan Basin, northeastern Chongqing City, and southeastern Guizhou Province. The drought frequency was highest at the stage from transplanting to tasseling, followed by the stage from grain filling to maturity, and was lowest at the stage from tasseling to grain filling. Mp was suitable for monitoring the rice drought in Southwest China, and could be used as a reference for the rice planting areas without irrigation data. PMID- 26995918 TI - [Comparison of potential yield and resource utilization efficiency of main food crops in three provinces of Northeast China under climate change]. AB - Based on the daily data of 65 meteorological stations from 1961 to 2010 and the crop phenology data in the potential cultivation zones of thermophilic and chimonophilous crops in Northeast China, the crop potential yields were calculated through step-by-step correction method. The spatio-temporal distribution of the crop potential yields at different levels was analyzed. And then we quantified the limitations of temperature and precipitation on the crop potential yields and compared the differences in the climatic resource utilization efficiency. The results showed that the thermal potential yields of six crops (including maize, rice, spring wheat, sorghum, millet and soybean) during the period 1961-2010 deceased from west to east. The climatic potential yields of the five crops (spring wheat not included) were higher in the south than in the north. The potential yield loss rate due to temperature limitations of the six crops presented a spatial distribution pattern and was higher in the east than in the west. Among the six main crops, the yield potential loss rate due to temperature limitation of the soybean was the highest (51%), and those of the other crops fluctuated within the range of 33%-41%. The potential yield loss rate due to water limitation had an obvious regional difference, and was high in Songnen Plain and Changbai Mountains. The potential yield loss rate of spring wheat was the highest (50%), and those of the other four rainfed crops fluctuated within the range of 8%-10%. The solar energy utilization efficiency of the six main crops ranged from 0.9% to 2.7%, in the order of maize> sorghum>rice>millet>spring wheat>soybean. The precipitation utilization efficiency of the maize, sorghum, spring wheat, millet and soybean under rainfed conditions ranged from 8 to 35 kg . hm-2 . mm-1, in the order of maize>sorghum>spring wheat>millet>soybean. In those areas with lower efficiency of solar energy utilization and precipitation utilization, such as Changbai Mountains and the south of Lesser Khingan Mountains, measures could be taken to increase the efficiency of resource utilization such as rational close-planting, selection of droughtresistant varieties, proper and timely fertilization, farming for soil water storage, optimization of crop layout and so on. PMID- 26995920 TI - [Improvement of root parameters in land surface model (LSM )and its effect on the simulated results]. AB - In order to improve root parameterization in land surface model, the sub-model for root in CERES-Maize was coupled in the SSiB2 after calibrating of maize parameters in SSiB2. The effects of two improved root parameterization schemes on simulated results of land surface flux were analyzed. Results indicated that simulation accuracy of land surface flux was enhanced when the root module provided root depth only with the SSiB2 model (scheme I). Correlation coefficients between observed and simulated values of latent flux and sensible flux increased during the whole growing season, and RMSE of linear fitting decreased. Simulation accuracy of CO2 flux was also enhanced from 121 days after sowing to mature period. On the other hand, simulation accuracy of the flux was enhanced when the root module provided root depth and root length density simultaneously for the SSiB2 model (scheme II). Compared with the scheme I, the scheme II was more comprehensive, while its simulation accuracy of land surface flux decreased. The improved root parameterization in the SSiB2 model was better than the original one, which made simulated accuracy of land-atmospheric flux improved. The scheme II overestimated root relative growth in the surface layer soil, so its simulated accuracy was lower than that of the scheme I. PMID- 26995921 TI - [Freezing resistance and injury indices for different cultivars of winter-spring wheat in Huang-Huai-Hai Plain. I . Comparison of freezing resistance for different cultivars of winter-spring wheat during mid-winter period]. AB - The relationships between mortality rate and low temperature for different cultivars of winter-spring wheat during mid-winter period were identified through two-year outdoor potting experiments and indoor manually controlled freezing experiments. We defined the lethally critical temperature and the density of antifreeze capability when the mortality rate reached 10%, 20% and 50% for different cultivars of winter-spring wheat during mid-winter period. The strong winterness wheat (Yanda 1817 and Jing 411) showed the best freezing resistance and the 50%-lethal temperatures (LT50) of these two cultivars were -21.5 degrees C and -21.2 degrees C, respectively. The freezing resistance of winterness wheat and weak-winternes wheat were worse than that of strong-winterness wheat. The LT50 of winterness wheat cultivars Nongda 211 and Nongda 5363 were -21.1 degrees C and -20.3 degrees C, while that of weak-winterness wheat cultivars Zheng 366 and Ping' an 8 were -18.5 degrees C and -18.4 degrees C , respectively. Springness wheat (Zheng 9023 and Yanzhan 4110) showed the worst freezing resistance, and the LT50 were -15.4 degrees C and -14.7 degrees C, respectively. When temperature declined to freezing injury occurred, mortality rate increment for weak-winterness wheat was the highest for each 1 degrees C decrease. The mortality rates of weak-winterness wheat cultivars Zheng 366 and Ping' an 8 increased by 16.8% and 25.8%, and that of winterness wheat cultivars Nongda 211 and Nongda 5363 increased by 14.7% and 18.9%. The mortality rate of strong-winterness wheat cultivars Yanda 1817 and Jing 411 increased by 15.4% and 13.1%, and that of springiness wheat cultivas Zheng 9023 and Yanzhan 4110 increased by 13.8% and 15.1%. Comparatively, if temperature decreased continuously after the occurrence of freezing injury, the weak-winterness wheat would suffer greater risk. PMID- 26995922 TI - [Assessment of landscape ecological security and optimization of landscape pattern based on spatial principal component analysis and resistance model in arid inland area: A case study of Ganzhou District, Zhangye City, Northwest China]. AB - Starting from ecological environment of inland river in arid area, the distribution of ecological security pattern of Ganzhou District was obtained by using the theory of landscape ecology, spatial principal component analysis (SPCA) and GIS techniques. Ten factors such as altitude, slope, soil erosion, vegetation coverage, and distance from road, were selected as the constraint conditions. According to the minimum cumulative resistance (MCR) model of landscape, the ecological corridor and nodes were established to optimize the structure and function of ecological function network. The results showed that the comprehensive ecological security situation of the research area was on the average. Area of moderate level of security was 1318.7 km2, being the largest and accounting for 36.7% of the research area. The area of low level of security was mainly located in the northern part and accounted for 19.9% of the study area. With points, lines and surfaces being interlaced, a regional ecological network was constructed, which was consisted of six ecological corridor, 14 ecological nodes, a large ecological source region and a plurality of small area source region, and could effectively improve ecological security level of the study area. PMID- 26995923 TI - [Ecosystem services valuation of Qinghai Lake]. AB - Qinghai Lake is the largest inland and salt water lake in China, and provides important ecosystem services to beneficiaries. Economic valuation of wetland ecosystem services from Qinghai Lake can reveal the direct contribution of lake ecosystems to beneficiaries using economic data, which can advance the incorporation of wetland protection of Qinghai Lake into economic tradeoffs and decision analyses. In this paper, we established a final ecosystem services valuation system based on the underlying ecological mechanisms and regional socio economic conditions. We then evaluated the eco-economic value provided by the wetlands at Qinghai Lake to beneficiaries in 2012 using the market value method, replacement cost method, zonal travel cost method, and contingent valuation method. According to the valuation result, the total economic values of the final ecosystem services provided by the wetlands at Qinghai Lake were estimated to be 6749.08 x 10(8) yuan RMB in 2012, among which the value of water storage service and climate regulation service were 4797.57 x 10(8) and 1929.34 x 10(8) yuan RMB, accounting for 71.1% and 28.6% of the total value, respectively. The economic value of the 8 final ecosystem services was ranked from greatest to lowest as: water storage service > climate regulation service > recreation and tourism service > non-use value > oxygen release service > raw material production service > carbon sequestration service > food production service. The evaluation result of this paper reflects the substantial value that the wetlands of Qinghai Lake provide to beneficiaries using monetary values, which has the potential to help increase wetland protection awareness among the public and decision-makers, and inform managers about ways to create ecological compensation incentives. The final ecosystem service evaluation system presented in this paper will offer guidance on separating intermediate services and final services, and establishing monitoring programs for dynamic ecosystem services valuation with the aim of helping improve management outcomes. PMID- 26995924 TI - [Relationships between characteristics of ground bryophyte communities and environmental factors in urban area of Chongqing, China]. AB - The present study focused on bryophyte species composition, species diversity and the relationship between bryophyte communities and environmental factors in urban area of Chongqing City, by using biodiversity indices and the canonical correspondence analysis (CCA), based on the data of 44 plots. The results revealed that 86 species belonging to 43 genera and 25 families were found in saxicolous bryophyte communities, while 46 species belonging to 28 genera and 22 families were found in terricolous ones. The diversity indices of both saxicolous and terricolous bryophyte communities from campuses were higher than those of parks, natural scenic resorts, Jinyunshan National Nature Reserve. TWINSPAN classified saxicolous and terricolous bryophyte communities into three and two groups, respectively. CCA results showed canopy density was the major environmental factor of saxicolous bryophyte communities influencing bryophyte distribution in parks and campuses, whereas altitude, relative humidity and human disturbance were the major environmental factors in natural scenic resorts and nature reserve. Soil pH, canopy density and human disturbance were the major environmental factors in terricolous bryophyte communities in parks and campuses, whereas altitude, relative humidity and water content of the soil were the major environmental factors in those of natural scenic resorts and nature reserve. PMID- 26995925 TI - [hnprovement on the growth and nutrient absorption of Iris hexagona by exogenous salicylic acid under Cd stress]. AB - The effects of exogenous salicylic acid (SA) pretreatment on the biomass, water content, photosynthesis, root vigor, Cd accumulation, nutrient absorption and antioxidant enzyme activity of Iris hexagona under Cd stress were studied by using Hoagland solution culture. The results showed that SA pretreatment promoted dry mass, root vigor and net photosynthetic rate of Cd-stressed I. hexagona seedlings. Compared with only Cd treatment, the Cd accumulation of Cd-treated plants with SA pretreatment remained unaffected, however,. SA pretreatment increased contents of N, P, S, and decreased K content. Activities of antioxidant enzymes of Cd-treated seedling root were increased under SA pretreatment. In conclusion, the improvement on growth of I. hexagona by SA pretreatment under Cd stress was attributed to improving Cd tolerance rather than reducing Cd uptake. The regulation of mineral element accumulation and the increase of antioxidant enzyme activities could be explained for Cd resistance improvement induced by salicylic acid. PMID- 26995926 TI - [Population difference of polypores in northwest and southeast of China]. AB - Polypores are an important group of wood-rotting fungi and play a key role in decomposing wood in the forest ecosystem. Based on field investigations and laboratory analysis, fungal flora and diversity composition of polypores in Tianshan Moutains, Qilian Mountains, Baotianman Nature Reserve and Wuyi Mountains were analyzed. In total, 72 polypore species were found in Tianshan Mountains, 99 in Qilian Mountains, 124 in Baotianman Nature Reserve and 156 in Wuyi Mountains. There were fourteen common species in the four zones. The biogeography could be divided into 4 groups at genera level of the four zones, the important elements were North temperate element and cosmopolitan element, and floristic analysis showed a distinct north temperate character. The proportion of white rot polypores in the four zones increased from northwest to southeast of China, while the proportion of brown rot polypores decreased. Polypores preferentially grew on angiosperm trees compared to gymnosperm trees. Among the four zones, polypores in Baotianman had the highest proportion of species living on angiosperm trees. Rare and threatened species in Tianshan Mountains and Qilian Mountains were mainly found on conifer trees, while in the other two zones, most rare and threatened species were found on broadleaf trees. Generally, the distinctions of these four areas were mainly affected by the forest type. PMID- 26995927 TI - [Inhibition of Bacillus pumilus AR03 on Alternaria alternata and Erysiphe cichoracearum on tobacco]. AB - This study aimed to evaluate the efficiency of Bacillus pumilus AR03 against Altenaria alternata and Erysiphe cichoracearum. The antagonistic activities were studied in the way of co-culture on plate, inhibition of pathogen conidia germination on concave slides and LB agar medium. In the investigation, the water suspension of living cells of strain AR03, at 3 x 10(8) cfu . mL-1 had a remarkable inhibition effect on hyphae growth and conidia germination of A. alternata and caused hyphae deformation, shorter and swollen nodes, winding hyphae accumulation, abnormal tubes with tips expanded or deformed. Conidia did not germinate and the tissues of compartment became swollen or formed a round spherical bubble. In addition, the inhibition rate of conidia germination of E. cichoracearum was 91. 3% and 69. 3%, respectively when treated with strain AR03 at 1 x 10(7) cfu . mL-1 and 1.5 x 10(6) cfu . mL-1. Conidia treated by living cells of AR03 became swollen, deformed, the protoplasm of conidia shrinked, disintegrated gradually and separated from the conidia wall. And some conidia were hollow because the protoplasm leaked out from inside. Greenhouse results revealed that the effects of living cells of AR03 with different concentrations were significantly different. Bacterial suspension of AR03 at 3 x 10(8) cfu . mL 1 was strongly antagonistic to E. cichoracearum with the control efficiencies 7 days and 15 days after treatment of two spays being 83.8% and 90.3%, respectively, while the control efficiencies of AR03 at 3 x 10(6) cfu . mL-1 were 70.0% and 73.3%, respectively. Strain AR03 had a long persistence against powdery mildew more than 30 days. PMID- 26995928 TI - [Evaluation of ivermectin's reproductive toxicity to male Carassius auratus]. AB - As a new type of antiparasitic drugs, ivermectin (IVM) has been widely applied in agriculture, stock raising and aquaculture in China because of its broad spectrum and high efficiency. In order to evaluate the IVM' s reproductive toxicity to male Crucian carp (Carassius auratus), IVM was orally given to the experimental fish with different dosages and the gonadosomatic index (GSI), sexual hormone contents (including testosterone and estradiol) in serum and testis, gamma aminobutyric acid content in serum and brain tissues, ultra-structure of spermatozoa and gonadal tissue in fish were determined in this study. The experimental fish were classified into A, B, C and D groups corresponding to the different dosages of IVM (0, 0.3, 0.9 and 1.5 mg . kg-1, respectively once a day for 3 days continuously). Several indices in fish were detected after 8 days self purification. The results indicated that GSI gradually decreased with the increase of drug dosage, and GSI in groups C and D was significantly lower than that in group A. The contents of testosterone, estradiol and y-aminobutyric acid exhibited a trend of first increasing and then decreasing and reached the peak at group B. Sperm longevity gradually decreased and the motion time also decreased in II, III and IV level sperms with the increasing dosage of IVM, which appeared to be especially obvious in group C and D. No obvious differences were found in the ultra-structure of spermatozoa and gonadal tissues. In conclusion, this study suggested that IVM had no obvious reproductive toxicity to male Crucian carp at the normal therapeutic dosage but could cause serious potential reproductive toxicity to fish at a high concentration. PMID- 26995929 TI - [Vermicomposting of different organic materials and three-dimensional excitation emission matrix fluorescence spectroscopic characterization of their dissolved organic matter]. AB - In this experiment, different proportions of the cattle manure, tea-leaf, herb and mushroom residues, were used as food for earthworm (Eisenia fetida) to study the growth of the earth-worm. Then the characteristics and transformation of nutrient content and three-dimensional excitation emission matrix fluorescence (3DEEM) of dissolved organic matter (DOM) during vermistabilization were investigated by means of chemical and spectroscopic methods. The result showed that the mixture of different ratios of cattle manure with herb residue, and cattle manure with tea-leaf were conducive to the growth of earthworm, while the materials compounded with mushroom residue inhibited the growth of earthworm. With the increasing time of verimcomposting, the pH in vermicompost tended to be circumneutral and weakly acidic, and there were increases in electrical conductivity, and the contents of total nitrogen, total phosphorus, available nitrogen, and available phosphorus, while the total potassium and available potassium increased first and then decreased, and the organic matter content decreased. 3DEEM and fluorescence regional integration results indicated that, the fluorescence of protein-like fluorescence peaks declined significantly, while the intensity of humic-like fluorescence peak increased significantly in DOM. Vermicomposting process might change the compositions of DOM with elevated concentrations of humic acid and fulvic acid in the organics. In all, this study suggested the suitability of 3DEEM for monitoring the organics transformation and assessing the maturity in the vermicomposting. PMID- 26995930 TI - [Exogenous Sr2+ sedimentation on otolith of chum salmon embryos]. AB - To explore the exogenous Sr2+ sedimentation on otolith of chum salmon embryos, chum salmon embryos were exposed to culture water contained Sr2+ at Sr2+ concentration of 50, 100, 200 or 400 mg . L-1 for 48 h to imitate Sr2+ sedimentation. After a culturing period of 12 d and 100 d, the otoliths of the chum salmon were taken to detect exogenous Sr2+ sedimentation with electro-probe microanalyzer (EPMA). The results showed that obvious deep red strontium signatures were produced in the otolith of chum salmon at different concentrations of Sr2+. The mean and extreme values of peak strontium area were not stable for the same Sr2+ dose, but the lowest of all the peak values was 35.1 times as much as that of control. Overall, the strontium value increased with the increase of Sr2+concentration. The strontium peak had no signs of abating after a culture period of 100 d. The results also showed that strontium was gradually deposited in the otolith, and had obvious hysteresis to immersion. Strontium sedimentation could also return to a normal level after the peak. These characteristics accorded exactly with the requirement of discharge tag technology, which indicated that exogenous Sr2+ was suitable in the marking of salmon otolith. PMID- 26995931 TI - [Niche and interspecific association of nekton in the south coastal waters of Cangnan, Zhe-jiang, China]. AB - In this paper, the interaction between the species Population were analyzed based on the data of major nekton species in the south coastal waters of Cangnan in spring and autumn 2014. A series of methods including niche breadth, niche overlap, chi2 - test and association coefficient (AC) based on a 2x2 contingency table were used. The results showed that the major nekton species in the south coastal waters of Cangnan were classified into three groups, i.e. wide niche breadth species, moderate niche breadth species and narrow niche breadth species based on the niche breadth values. The wide niche breadth species of nekton were Harpodon nehereus, Portunus trituberculatus, mantis shrimp and other 2 species. The moderate niche breadth species of nekton were Collichthys lucidus, Parapenaeopsis hardwickii, Parapenaeopsis tenella and other 5 species. While the species with narrow niche breadths were Charybdis japonica, Amblychaeturichthys hexanema, Palaemon gravieri and other 7 species. There were great differences in the niche overlap values among the major nekton populations, with the maximum value of 0.93 and the minimum of 0, which indicated that resource utilization competition in some nekton might exist. The results of variance ratio analysis for major nekton in the south coastal waters of Cangnan showed that they were significantly positively correlated. chi2 - test results showed that there were significantly interspecific association for 78 species pairs (chi2>=3.841), among which more association coefficients (AC) of species pairs are positive. PMID- 26995932 TI - [Effects of high temperature on Bt protein content and nitrogen metabolic physiology in boll wall of Bt cotton]. AB - Bt cotton cultivar Sikang 1 (a conventional cultivar) and Sikang 3 (a hybrid cultivar) from China, and 99B (a conventional cultivar) and Daiza 1 (a hybrid cultivar) from USA were selected as experimental materials, the ball wall Bt protein content and nitrogen metabolic physiology were investigated under different high temperature levels at peak boll stage. The results showed that the Bt protein content of boll wall decreased with the increasing temperature. Compared with the control (32 degrees C, the boll wall Bt protein content decreased significantly when the temperature was above 38 degrees C for the conventional cultivars and above 40 degrees C for the hybrid cultivars. The Bt protein contents of cultivar Sikang 1 and 99B decreased by 53.0% and 69.5% respectively with the temperature at 38 degrees C, and that of cultivar Sikang 3 and Daiza 1 decreased by 64.8% and 54.1% respectively with the temperature at 40 degrees C. Greater reductions in the boll wall soluble protein contents and GPT activities, larger increments for the boll wall free amino acid contents and proteinsase activities were also observed when the boll wall Bt protein content was significantly reduced. Therefore, high temperature resulted in the reduction of Bt protein synthesis and increase of the insecticidal protein degradation in the boll wall significantly, which caused the reductions in boll wall Bt protein content and insect resistance. PMID- 26995933 TI - [Research progress on water footprint in agricultural products]. AB - Water is one of the important resources in human activities. Scientifically and rationally evaluating the effects of human activities on water resources is important for sustainable water resource management. The innovative concepts of water footprint (WF) distinguished the human water consumption into green water, blue water and grey water which extended the evaluation methods in sustainable utilization of water resources. Concepts of WF based on virtual water (VW) and based on life cycle assessment (LCA) both combined water quality and water quantity are now the focuses in agricultural water management researches. Theory of WF based on VW includes the calculation of green, blue and grey WF as well as the evaluation of the sustainability of water environment. Theory of WF based on LCA reflects the overall impact of consumptive and degradative water use on the environment. The purpose of this article was to elaborate the research progresses in theoretical calculation methods and environmental sustainability assessment of the two water footprint theories and then to analyze the differentiation of these two methodologies in describing the consumptive water use in agriculture and its effects on environment. Finally, some future research aspects on water footprint were provided. PMID- 26995934 TI - [Novel transmission element of antibiotic resistance genes ISCR and its ecological risk]. AB - Antibiotic resistance genes (ARGs) as emerging environmental pollutants have become the focus of attention of many disciplines. The transmission and dissemination of ARGs in various environmental media has great hazards to environment and poses serious threat to human health. ISCR (insertion sequence common regions) elements are newly discovered resistance genes transmission elements. Because of the special genetic structure, ISCR elements can move any adjacent DNA sequences by rolling-circle replication and homologous recombination, and have become the efficient transmission elements of ARGs among different DNA molecules or bacterial species. Around the world, 27 members of the ISCR family have been discovered up to now. A lot of circumstantial evidence has indicated that ISCR elements may be associated with the mobility and transmission of kinds of ARGs, especially multiple drug resistance genes (MDR). In this review, we described some aspects of ISCR elements, including the horizontal transfer of ARGs, structural characteristics of ISCRs, classification of ISCRs and their related ARGs, research methods of these elements, possible ecological risk of ISCRs and proposal of research directions, hoping to provide help for further related research in the future. PMID- 26995935 TI - [Mechanisms of Cr (VI) toxicity to fish in aquatic environment: A review]. AB - With increasing consumption and applications of chromium in metallurgy, electroplating, tanning process and stainless steel industry, chromium contamination has become a global environmental problem. In general, Cr(VI) has higher permeability across the cell membrane than Cr(III) and hence is considered more toxic than Cr(III). Oxidative stress could be induced following reactive oxygen species (ROS) normally produced in fish under Cr(VI) exposure due to its variable valences. Furthermore, the intermediates of Cr, e.g. Cr(V) and Cr(IV) , produced by cellular reduction processes can bind with DNA and result in mutagenic effects. These combined effects will threaten the growth, development and population structure of different fish species. In this paper, we reviewed published results on the toxic effects of Cr(VI) in fish at levels of molecules, tissues, organs and individuals. The mechanisms of toxicity and detoxification of Cr(VI) in various aspects were discussed. In addition, we also put forward perspectives on the toxicity of chromium in aquatic organisms. PMID- 26995936 TI - [Biosynthesis and endocrine regulation of sex pheromones in moth]. AB - The crucial importance of sex pheromones in driving mating behaviors in moths has been well demonstrated in the process of sexual communication between individuals that produce and recognize species specific pheromones. Sex-pheromone molecules from different moth species are chemically characteristic, showing different terminal functional groups, various carbon chain lengths, different position and configuration of double bond system. This review summarized information on the biosynthetic pathways and enzymes involved in producing pheromone molecules in different moths. Then we listed the components and their ratios in the sex pheromones of 15 moth species belonging to different subfamilies in Noctuidae. We also discussed the various viewpoints regarding how sex pheromones with specific ratios are produced. In the discussion we attempted to classify the pheromone molecules based on their producers, characteristics of their functional groups and carbon chain lengths. In particular, composition and ratio variations of pheromones in closely related species or within a species were compared, and the possible molecular mechanisms for these variations and their evolutionary significance were discussed. Finally, we reviewed the endocrine regulation and signal transduction pathways, in which the pheromone biosynthesis activating neuropeptide (PBAN) is involved. Comparing the biosynthetic pathways of sex pheromones among different species, this article aimed to reveal the common principles in pheromone biosynthesis among moth species and the characteristic features associated with the evolutionary course of individual species. Subsequently, some future research directions were proposed. PMID- 26995937 TI - Insulin-like growth factor-1 isoforms in human ovary. Preliminary report on the expression of the IGF-1 gene in PCOS patients and healthy controls. AB - Insulin-like growth factor 1 (IGF-1), produced and secreted locally may affect the mechanisms of folliculogenesis and cause ovarian dysfunction, characteristic of PCOS. The expression of the IGF-1 gene gives rise to three different isoforms of the original molecule. Until now, the role of IGF-1 isoforms has been documented in the repair processes of damaged muscle fibers, cardomyocytes, hepatocytes, and neurons. The literature offers no reports on the presence and role of IGF-1 isoforms in the ovary OBJECTIVES: The aim of the study was to assess the IGF-1A, B and C isoforms at the level of IGF-1 gene transcription in the ovaries of PCOS women and healthy controls. MATERIAL AND METHODS: Serum samples and ovarian tissues from PCOS women, treated and non-treated with metformin (PCOS M(+); n = 12 and PCOS M(-), n = 37, respectively), and controls (n = 21) were obtained. The expression of mRNA species of IGF-1 in the ovaries was determined by quantitative RT-PCR. RESULTS: The presence of transcripts of three types of IGF-1 isoforms was observed in healthy controls and PCOS patients, regardless of metformin treatment. Total expression of all isoforms was higher in the M(-)(Me-26640) group as compared to the M(+)(Me- 13470) group, as well as controls (Me-17030)-(not significant, p = 0.061). Similar results for IGF-1A were obtained in all groups. The relative expression of IGF-1A was lower in the M( )(86.02%) group and differed statistically from controls (91.38%) (p = 0.011). CONCLUSIONS: We detected the presence of mRNA for three IGF-1 isoforms in human ovary. To the best of our knowledge, this has been the first report on the presence of mRNA for three IGF-1 isoforms in human ovary. We found differences in the relative expression of IGF-1A isoforms between the investigated groups. PMID- 26995938 TI - [Rectovaginal endometriosis--analysis of 160 cases]. AB - OBJECTIVES: The aim of the study was a retrospective analysis of the medical records of patients who underwent surgery due to deep infiltrating rectovaginal endometriosis (mainly with the use of the 'shaving' technique). MATERIAL AND METHODS: We analysed 160 cases of patients who underwent surgery due to the deep infiltrating rectovaginal endometriosis in our ward between 2003-2014. Depending on lesion localization, disease severity and clinical characteristics, three possible ways of operation were proposed: laparoscopic, vaginal or a combined vagino-laparoscopic approach. RESULTS: A total of 120 patients underwent laparoscopic removal of the endometrial lesions, whereas 17 were operated vaginally and 23 with the use of the combined approach. Nodule resection was successfully performed in all cases. The combined vagino-laparoscopic operations were characterized by the longest operating time. The rate of perioperative complications was low in the group of patients who underwent laparoscopic or combined operations. The necessity of bowel wall suturing occurred in 15 cases. This procedure was performed in order to strengthen the bowel wall (in cases when no perforation occurred) or due to bowel resection during surgery. Unexpected bowel perforation occurred in only 5 cases. Conclusions: Vaginal, laparoscopic and the combined vagino-laparoscopic surgeries can be safely performed in cases of deep rectovaginal endometriosis. PMID- 26995939 TI - [Recurrent ovarian cancer--qualification and results of surgical treatment]. AB - INTRODUCTION: Complete tumor cytoreduction seems to be beneficial for platinum sensitive women with recurrent ovarian cancer (ROC). Selection of patients who might have a chance for complete debulking constitutes a real challenge. Several predictive models defining a chance for complete cytoreduction and help in patient selection for surgery have been developed. OBJECTIVES: The aim of the study was to evaluate the effectiveness of selected models in one clinical center and the impact of complete resection on treatment outcome. MATERIAL AND METHODS: A total of 17 patients with ROC, diagnosed at least 6 months after first-line chemotherapy were recruited for the study. The inclusion criteria were based on the AGO-score (DESKTOP I trial). The group were retrospectively analyzed based on the predictive model International Collaborative Cohort Score (Tian- score). The end point was the percentage of complete cytoreduction. Also, postoperative complications and progression-free survival (PFS) were evaluated. RESULTS: Out of 17 patients who meet the criteria of the the AGO-score, complete debulking was achieved in 13 (76.47%) cases. Comparing the results of the Tian-score, 12 (100%) patients who were considered to be at 'low-risk of surgical failure' were debulked optimally In addition, complete debulking was achieved in 1 patient from the high-risk group. In all optimally operated patients, the number of changes detected during pre-operative imaging was <= 3. In 11 patients after complete cytoreduction there was another relapse. The median of PFS was 16 months. CONCLUSIONS: The applied predictive models have proven to be effective in selecting patients who will benefit from surgical treatment of ROC. PMID- 26995940 TI - Polymorphisms of collagen 1A1 (COL1A1) gene and their relation to bone mineral density in postmenopausal women. AB - OBJECTIVES: The goal of this study was to evaluate the frequency of Sp1 +1245G>T (rs 1800012) and -199 7G>T (rs 1107946) COL1A1 gene polymorphisms in postmenopausal women with osteoporosis and osteopenia as well as assessing their relations with the clinical parameters and parameters of bone turnover. STUDY DESIGN: The study included 538 (236 postmenopausal and 302 healthy reproductive) Polish women. The postmenopausal group included women with osteoporosis (n = 90), osteopenia (n = 90), as well as healthy individuals (n = 56). All women of reproductive age were healthy BMD was marked in the L2-L4 lumbar region of the spine using dual energy X-ray absorptiometry (DXA). Genomic DNA was isolated from peripheral blood, the genotype frequency of investigated polymorphisms was determined by PCR-RFLP technique. RESULTS: The frequency of Sp1 +1245G>T and 1997G>T polymorphisms of COL1A1 gene showed no statistically significant differences between group with osteoporosis, osteopenia and correct T-score and women of reproductive age. In postmenopausal women it was found that osteopenia and osteoporosis were correlated with age, birth weight, age of last menses occurrence, height, body weight and BMI value. Clinical parameters in all groups of women did not show any statistically significant correlation with frequency of Sp1 +1245G>T and -1997G>T COL1A1 polymorphisms. CONCLUSIONS: An evaluation of Sp1 +1245G>T (rs1800012) and -1997G>T(rs 1107946) COL1A1 polymorphisms showed any influence of these genetic variants on osteoporosis development in Polish postmenopausal women. The presented correlation between osteoporosis and age, birth weight, age of last menses occurrence, height, body weight and BMI value confirms the important role of environmental factors in disease etiology. PMID- 26995941 TI - [Correlation between ultrasonographic measurement of fetal thigh soft-tissue thickness and selected fetal ultrasonographic and maternal anthropometric parameters]. AB - AIM: The aim of the study was to assess a correlation between ultrasonographic measurement of fetal thigh soft-tissue thickness (FTSTT) and selected fetal ultrasonographic and maternal anthropometric parameters. MATERIAL AND METHODS: A total of 140 women with a singleton term pregnancy were included in the study Anthropometric maternal and fetal measurements were assessed. Fetal weight was estimated with the Hadlock formula using head circumference (HC), abdomen circumference (AC), biparietal diameter (BPD), and femoral length (FL). FTSTT was measured using the method of Scioscia M. et al. Then, statistical analysis of the correlation between FTSTT and maternal anthropometric and fetal ultrasonographic parameters was performed. RESULTS: A statistically significant correlation was found between ultrasonographically estimated fetal weight and BPD, HC, AC, FL and FTSTT, as well as between FTSTT and neonatal birthweight and length, and maternal pre-pregnancy and pre-delivery weight. This correlation was not found between FTSTT and maternal BMI and weight gain during pregnancy A statistically significant correlation was detected between FTSTT and neonatal birthweight of newborns born between 38 and 40 weeks of gestation but no such correlation was found at 37 and 41 weeks of gestation. In addition, no statistically significant difference was observed in the measurement of FTSTT between physiological pregnancies and those complicated by diabetes. FTSTT measurements in fetuses with macrosomia (real and determined on the basis of ultrasound examination) were not statistically different from those of fetuses without macrosomia. CONCLUSIONS: FTSTT measurement may be helpful in estimating fetal weight, but it is not useful in the diagnosis of fetal macrosomia. PMID- 26995942 TI - Does prior knowledge of maternal age affect judgment of operators measuring nuchal translucency? AB - OBJECTIVES: To test the hypothesis that, in real life standard clinical practice, knowledge of maternal age (MA) by operators measuring nuchal translucency (NT) for screening of aneuploidy may influence their judgment, resulting in a tendency to over-measurement in older women. MATERIAL AND METHODS: We retrospectively analyzed the correlation between MA and NT MoMs in data from a group of operators from several clinical practices, with different levels of experience. RESULTS: We assessed 66,918 measurements by 41 operators. There was no association between NT and MA in all the measurements analyzed together In 3 experienced operators (N > 1900), there was a significant association between the variables, although all were negative and its effect size was very small (0.004, 0.006 and 0.01). However one of the less experienced operators (N = 47) had a statistically significant (p = 0.0002) and strong (R2 = 0.2634) association. We tested the hypothesis that this bias could occur in less experienced operators but time/experience would correct it. We did the same analyses for each set of 50 tests, sorted by date, for each operator up to the 7th set. No significant progression was identified in association with increase in experience. CONCLUSIONS: Our data does not support the hypothesis that operators might be biased towards over-measuring NT in older women. PMID- 26995943 TI - Significance of C-reactive protein in predicting fetal inflammatory response syndrome. AB - OBJECTIVES: The aim of the study was to identify and evaluate a possible correlation between C-reactive protein (CRP) concentration in maternal blood and the risk of developing fetal inflammatory syndrome (FIRS). MATERIAL AND METHODS: The study included 158 infants born at 22-34 weeks of gestation and their mothers. Umbilical cord blood cytokines were evaluated in immunoassay tests and maternal blood was tested for CRP concentration. RESULTS: The period of gestation was significantly shorter in the FIRS group as compared to the control group (29.5 +/- 3.1 vs. 32.2 +/- 2.4 weeks, p < 0.001). Gestational age was <= 30 weeks for 53.8% of the newborns in the FIRS group and 15.8% of the newborns in the control group (p < 0.001). Maternal CRP before, during and after labor was significantly higher in the FIRS group as compared to the control group (p < 0.001). Our study investigated the correlation between CRP in maternal blood and IL-6 concentration during the entire perinatal period (p < 0.001). CONCLUSION: CRP concentration in the FIRS group was significantly higher than in controls before, during, and after labor. Thus, it seems safe to conclude that changing concentration of inflammatory factors in maternal blood are closely related to FIRS. Elevated CRP in maternal blood might signify a progressing intrauterine infection and herald the development of FIRS. PMID- 26995944 TI - Assisted reproductive medicine in Poland --Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG) 2012 report. AB - OBJECTIVES: The aim of this report is to present data concerning results and complications related to infertility treatment using assisted reproductive technology (ART) and insemination (IUI) in Poland in 2012. MATERIAL AND METHODS: The report was prepared by the Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG), based on individual data provided by fertility clinics. Reporting was voluntary data were not subject to external verification. The report presents the availability and the structure of infertility treatment services, the number of procedures performed, their effectiveness and the most common complications. RESULTS: In 2014, 34 Polish fertility clinics provided information to the report, presenting data from 2012. The total number of reported treatment cycles using ART was 17,116 (incl. 10,714 fresh IVF/ICSI) and 14,727 IUI. The clinical pregnancy rate per cycle was on average 33.7% for fresh IVF/ICSI and 13.3% for IUI. The prevalence of multiple births was 15.7% and 6.2%, in case of IVF/ICSI and IUI methods respectively The most frequent complication in the course of treatment using ART was ovarian hyperstimulation syndrome (OHSS)--severe OHSS constituted 0.68% of all stimulated cycles. CONCLUSIONS: The SPiN PTG report shows the average effectiveness and safety of ART and was the only proof of responsibility and due diligence of fertility centres in Poland. However, due to the lack of a central register of fertility clinics, facultative participation in the report as well as incomplete information on pregnancy and delivery rate, the collected data do not reflect the full spectrum of Polish reproductive medicine. PMID- 26995945 TI - [Folate metabolism--epigenetic role of choline and vitamin B12 during pregnancy]. AB - Adequate choline intake during pregnancy is essential for proper fetal development. Nowadays studies suggest that even in high income countries regular pregnant women diet does not provide the satisfactory amount of choline. Choline demand during pregnancy is high and it seems to exceed present choline intake recommendations. Moreover lactation period also demands choline supplementation because of its high concentration in female milk. Numerous studies on animal model proved correlation between choline supplementation during pregnancy and proper fetal cognitive function development. Despite increased synthesis in maternal liver during pregnancy choline demand is much higher than common dietary uptake. Nowadays studies as to the nutritional recommendations during pregnancy concern also vitamin B12 supplementation. Vitamin B12 deficiency may be an important risk factor of neural tube defects development. Presented article contains a review of data on proper choline and vitamin B12 uptake during pregnancy and lactation and potential results of choline and vitamin B12 poor maternal status. PMID- 26995946 TI - [Is the PAP smear era coming to an end?]. AB - After the discovery of the role human papilloma virus (HPV) plays in the development of cervical cancer we are witnesses to a change in the conception and interpretation of cervical cancer prevention processes. Primary prevention gained a new tool in the form of HPV vaccines. Secondary prevention, i.e. detection of cervical intraepithelial neoplasia (GIN), acquired a new diagnostic method--the HPV test. Studies were initiated in order to determine the usefulness of HPV tests in cervical cancer prevention and screening. They revealed that the DNA HPV test used in screening has higher sensitivity in CIN detection than PAP smear and that HPV-negative patients are better and longer protected against developing cervical cancer in comparison to women with normal PAP smear results. HPV tests also possess a predictive value, which detects women more susceptible to developing cervical cancer in the future. PAP smear does not have a predictive value. Instead, it only detects a presence or an absence of neoplasia at that particular time. These results clearly indicate that the era of classic PAP smear is indeed coming to an end, replaced by a new primary CIN screening tool--HPV test. The entire cervical cancer screening system must therefore be redefined and reorganized. PMID- 26995947 TI - [Placenta percreta--a severe obstetric complication despite correct diagnosis--a case report]. AB - This paper presents a case of a pregnant woman with a history of two cesarean sections. The patient was admitted to the hospital because of vaginal bleeding. The ultrasound revealed a placenta covering the internal os. The placenta was characterized by heterogeneous echogenicity with visible irregular hypoechogenic areas and blurred border between the placenta and the cervix. Rich vascularity was observed on the border of the placenta, urethra and the urinary bladder. Cystoscopy showed severe congestion around the urethra. On the back wall of the bladder a slightly increased vascularity was seen, which did not allow to confirm or exclude placental ingrowth in the urinary bladder. At 38 weeks, the patient was scheduled for an elective cesarean section. A classic perpendicular incision and leaving the placenta in the uterine cavity were proposed. After opening the abdomen, a strong vascularization in the region of lower part of the uterus and the urinary bladder was seen. Uterine incision in the fundus and the posterior wall was performed. A female fetus (weight: 2950g, Apgar: 10,10) was born. Then, the umbilical cord was ligated with non-absorbable suture and inserted back into the uterus. However, due to the presence of abundant and persistent vaginal bleeding during the next few minutes, conversion to obstetric hysterectomy was required. During relaparotomy fragments of the placenta appeared on the right side after sliding the urinary bladder. The bladder and the left ureter were damaged during surgery. The urinary bladder was sewn after removal of the uterus. Next, the urologist anastomosed end-to-end the left ureter on the pigtail catheter In the third hour of operation, cardiac arrest was caused by ventricular fibrillation. Immediate resuscitation with defibrillation allowed to restore normal function of the cardiovascular system. Total blood loss during the operation was 3000-4000 ml. During surgery 10 units of packed RBCs, 7 units of fresh frozen plasma, and 4 units of cryoprecipitate were transfused. The patient received antibiotics and anticoagulation therapy. Polyuria was diagnosed in the following days of puerperium, accompanied by electrolyte disturbances in serum and urine. The patient was treated with vasopressin and the electrolyte disturbances were corrected. On day 10 postpartum, the urinary catheter was removed, and clear significant improvement and stabilization of renal function and patient health were obtained. The patient was discharged from the hospital on day 19 of the puerperium. In summary it is clear that the steadily increasing rate of cesarean deliveries may result in the future in an increased number of abnormal placentation cases. Abnormal placentation is one of the most important risk factors of severe obstetric complications, including perinatal massive hemorrhage, which can lead to abnormal organ perfusion with cardiac arrest. Therefore, prenatal diagnosis and identification of abnormal placentation are vital in order to plan adequately the date, place, and mode of delivery as well as to ensure the availability of highly qualified specialists in the field of obstetrics and anesthesia, and organize sufficient amount of blood products and blood substitutes. PMID- 26995948 TI - Urgent embolization of hemorrhagic choriocarcinoma liver metastases--case report and review of the literature. AB - We present a rare case of 23-year-old patient with metastatic choriocarcinoma that presented life threatening abdominal bleeding from liver metastases shortly after initiation of treatment with chemotherapy and was treated by emergency embolization of the hepatic vessels. Although the bleeding was controlled, the patient succumbed to the disease on the 15th day after admission. Conclusions: Incontrollable hemorrhagic complications are the most common cause of death in choriocarcinoma metastatic patients. Angioembolization is an effective way of ceasing the bleeding and a potentially life saving measure. PMID- 26995949 TI - [Recommendations of the Polish Gynecological Society expert panel on the use of Detramax in pregnancy]. PMID- 26995950 TI - [Cell-free fetal DNA testing in prenatal genetic screening. Polish Gynaecological Society and Polish Human Genetics Society guidelines]. PMID- 26995951 TI - [REGULATION OF EXTRARENAL ERYTHROPOIETIN PRODUCTION]. AB - The review describes the induction of erythropoietin gene expression in liver, reproouctive and hemopoietic systems during hypoxia or a state of proliferation. PMID- 26995952 TI - [CHANGES IN THE QUALITATIVE AND QUANTITATIVE COMPOSITION OF GUT MICROBIOTA IN RATS DURING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS]. AB - In this study, on the model of multiple sclerosis - experimental allergic encephalomyelitis (EAE), the dynamics of changes in the qualitative and quantitative composition of the intestinal microbiota in rats with symptoms of the disease and asymptomatic course were compared. It was found that the composition of the intestinal microbiota in rats with the clinical symptoms of EAE is shifted towards gram-negative opportunistic microorganisms of the genus Citrobacter, Prote- us, Klebsiella and enteropathogenic Escherichia coli. It has been shown that rats without clinical signs of EAE have higher levels of Faecalibacteriumprausnitzii. The significance of the complex changes in the composition of the intestinal microbiota, indicating long-lasting dysbiosis in rats during the development of EAE is discussing. PMID- 26995953 TI - [THE STUDY OF THE TEMPORAL PROPERTIES OF THE AUDITORY SENSORY TRACE FOR A SHORT DURATION STIMULI USING THE MISMATCH NEGATIVITY]. AB - The present article accesses the dependence of mismatch negativity of the human auditory event related potentials on the length of interstimulus interval. We employed passive oddball paradigm as a presentation method and simple tones were used as stimuli. This study was based on the assumption, that storage time of the memory trace, which is used for generation of mismatch negativity, is dependent on the length of the stimulus itself. As a result, the mismatch negativity was registered for short durations 11 ms stimuli. In such stimuli differences of amplitude of mismatch negativity depending on the length of interstimulus interval were also shown. Yet no such differences were found for stimuli of 20 ms and 30 ms. This result allows us to assume that storage time of memory trace of stimulus is directly proportional to the length of the stimulus itself when short interstimulus intervals are used. However, the increase of stimulus length over certain threshold does not show any changes in the properties of mismatch negativity. PMID- 26995954 TI - [THE EFFECT OF NEUROPEPTIDE Y ON SPIKE ACTIVITY OF NEURONS IN THE SUPRACHIASMATIC NUCLEUS OF RAT IN VITRO]. AB - In the experiments on sagittal hypothalamic slices of male Wistar rats, the effect of 10 nM neuropeptide Y on the electrical activity of the suprachiasmatic nucleus neurons and spike information coding parameters were studied. Applications of neuropeptide Y induced a reduction of action potential frequency in 35 of 81 tested neurons, in 8 cells an increase in the parameter was observed; the remaining 38 neurons did not change their spike activity level. The decrease in spike frequency generation by neurons of the suprachiasmatic nucleus accompanied by an increase in both entropy of interspike interval distribution and mutual information between adjacent interspike intervals. These suggest an increased irregularity of the later as well as an increased patterning of spike information induced by neuropeptide Y. The obtained data indicate the ability of neuropeptide Y to modulate a level of activity and influence a spike code in a relatively numerous population of neurons in circadian oscillator of the suprachiasmatic nucleus. PMID- 26995955 TI - [CROSS-TALK BETWEEN 5-HT1A AND 5-HT7 RECEPTORS: ROLE IN THE AUTOREGULATION OF THE BRAIN SEROTONIN SYSTEM AND IN MECHANISM OF ANTIDEPRESSANTS ACTION]. AB - Recent studies considerably extended our knowledge of the mechanisms and physiological role of the interaction between different receptors in the brain. Current review summarizes data on the formation of receptor complexes and the role of such complexes in the autoregulation of the brain serotonin system, behavioral abnormalities and mechanism of antidepressants action. Particular attention is paid to 5-HT1A and 5-HT7 receptor heterodimers. The results described in the present review indicate that: i) dimerization and formation of mobile receptor complexes is a common feature for the members of G-protein coupled receptor superfamily; ii) 5-HT7 receptor appears to be a modulator for 5 HT1A receptor - the key autoregulator of the brain serotonin system; iii) 5 HT1A/5-HT7 receptor complexes formation is one of the mechanisms for inactivation and desensitization of the 5-HTIA receptors in the brain; iv) differences in the 5-HT7 receptor and 5-HTIA/5-HT7 heterodimers density define different sensitivity of pre- and postsynaptic 5-HTlA receptors to chronic treatment with selective serotonin reuptake inhibitors. PMID- 26995956 TI - [ELECTRIC STIMULATION OF VAGUS NERVE MODULATES A PROPAGATION OF OXYGEN EPILEPSY IN RABBITS]. AB - The activation of autonomic afferents (achieved through the vagus nerve (VN) electrical stimulation) on CNS O2 toxicity and cardiovascular function was investigated. In conscious rabbits at 5 ATA 02, prodromal signs of CNS O2 toxicity and convulsion latency were determined with and without vagus nerve (VN) stimulation. EEG, ECG and respiration were also recorded. In rabbits at 5 ATA, sympathetic overdrive and specific patterns on the EEG (synchronization of slow waves), ECG (tachycardia) and respiration (respiratory minute volume increase) preceded motor convulsions. Vagus nerve stimulation increased parasympathetic component of autonomic drive and significantly delayed prodromal signs of oxygen toxicity and convulsion latency. Autonomic afferent input to the brain is a novel target for preventing CNS toxicity in HBO2. PMID- 26995957 TI - [THE INDICATORS OF GROWTH AND MYOGENESIS IN THE GLYCOLYTIC AND OXIDATIVE MUSCLES OF THE RAT AFTER INDIRECT ELECTROSTIMULATION]. AB - A comparative analysis of the signaling pathways activity and gene expression in the red (RG) and white (WG) parts of the gastrocnemius muscle of rat after a series of short (1 s) tetanic contractions induced by motor nerve stimulation at a frequency of 100 Hz and with an amplitude that provides activation of all motor units of the muscle. WG compared to RG demonstrated a marked increase in the phosphorylation level of ERK1/2, although the increase in the phosphorylation of AMPK was not different in two muscles 2 h after the stimulation. Along with that, content of MyoD and myogenin mRNA in WG increased much higher than in RG, whereas the effect of stimulation on IGF-1, MaFbx and MuRF genes expression was weak and comparable in WG and RG. There was an increase of myostatin mRNA in RG. Thus, glycolytic muscle fibers of WG exhibit more pronounced regulatory shifts of hypertrophic character than oxidative muscle fibers of RG. PMID- 26995958 TI - [SIGNALING PATHWAYS REGULATING PROTEIN SYNTHESIS IN RAT SOLEUS MUSCLE DURING EARLY STAGES OF HINDLIMB UNLOADING]. AB - The impact of mechanical unloading (hindlimb suspension for 1-, 3- and 7 days) on the protein synthesis intensity and as well as intracellular signaling pathways controlling mRNA translation was investigated. The content of the key signaling molecules of the various anabolic signaling pathways was determined by Western blotting. The rate of protein synthesis was assessed using in vivo SUnSET technique. Hindlimb suspension (HS) within 24 hours resulted in a significant (p < 0.05) decrease in p-4E-BP 1 content and increase in p-p70s6k content in soleus muscle. Follo- wing three days of HS the content of p-AKT and p-90RSK1 was decreased (p <0.05). After 7 days of HS phosphorylation level of AKT and GSK 3beta was significantly reduced (p < 0.05) compared to the control group. We also observed a significant decrease in the amount of 28S rRNA in soleus following 3 and 7 days of HS. The rate of protein synthesis after 3 and 7 days of HS was decreased (p < 0.05) in comparison with the basal level. Our data suggest that the decrease in the protein synthesis rate in rat soleus during early stages of simulated microgravity could be associated with the impaired ribosome biogenesis as well as reduced activity of the mTORC1-independent signaling pathways. PMID- 26995959 TI - [THE INFLUENCE OF SEROTONIN TRANSPORTER AND MONOAMINE OXIDASE A GENES POLYMORPHISM ON PSYCHO-EMOTION AND KARYOLOGICAL STABILITY OF ATHLETES]. AB - The influence of polymorphism of the serotonin transporter and monoamine oxidase A genes, associated with man's aggressiveness on the psycho-emotional state and karyological status of single combat athletes. It was revealed that the carriers of less active ("short"), monoamine oxidase A gene variant have a high motivation to succeed and less rigidity and frustrated, compared to the carriers of more active ("long") version of the gene. Heterozygote carriers of less active ("short") variant of the serotonin transporter gene 5-HTTL had more physical aggression, guilt and were less frustrated compared with carriers of two long alleles. It has been revealed the association of studied genes with the karyological status of athletes. So fighters who are carriers of the short and long alleles of the serotonin transporter gene had more cells with nuclear abnormalities in the buccal epithelium than single combat athletes which both alleles were long. PMID- 26995960 TI - [SKIERS URINARY CATECHOLAMINES EXCRETION AT REST AND BY COMPETITIVE LOADS LENGTH VARIETY]. AB - While night sleeps urinary noradrenaline excretion of skilled skiers less than their untrained peers, but the difference in excretion of adrenaline is not revealed. By increasing the distance and time to overcome it during skiing catecholamine excretion is increased both - totally and per minute. Most urinary catecholamines detected at a distance of 50 km in low sliding: increased excretion of adrenaline - 84 times, and noradrenaline -95 times. These results shows that high qualificated skier's functional reserve of the sympathoadrenal system, is mobilize at long competitions for ten times higher than in rest. PMID- 26995961 TI - [NEGATIVE REGULATORS OF TUMOR SUPPRESSOR P53 IN THE CONTEXT OF ANTICANCER THERAPY]. AB - P53 protein is considered to be the major tumor suppressor in human cells. Cancer cells do not survive if the p53-mediated signaling pathways function properly. However, about half of all malignancies still express wild type p53. One of the explanations to this is that p53 is suppressed by overexpression of p53-specific E3-ubiquitin ligases: Mdm2, MdmX, Pirh2 and Cop1. Pharmacological inhibition of protein-protein interactions between p53 and these negative regulators is a promising therapeutic approach to treat cancers retaining wild type p53. To date, a series of chemical inhibitors of p53 interactions with Mdm2 and MdmX E3 ubiquitin ligases have been discovered and characterized. Several of them are in the early stages of clinical trials. Despite this fact, their clinical efficacy may be hampered by a number of reasons, including tumor-specific expression of multiple isoforms of the target E3-ligases, which become inert to treatment with small molecules. This and other biochemical mechanisms of possible resistance of tumor cells with wild type p53 to small molecules against its negative regulators will be discussed in this review. PMID- 26995962 TI - [ROLE OF CONTACTINS IN NEUROGENESIS IN HUMAN AND ANIMALS]. AB - Development of central and peripheral nervous system is one of the most complicated processes of embryogenesis. Dendritogenesis is an important component of this process because properties of dendritic branching define input and output signals received by neuron. Moreover, communications between neurons require transition of signal from dendrite of one neuron to axon of another, and this process of signal transduction underlies mechanisms of synaptic plasticity and memory formation. The neural cell adhesion molecules of the immunoglobulin superfamily involved in the control of dendritogenesis. In current review we focus our attention on 6 members of this adhesion molecules family: contactins 1 6. The contactins are proteins that control key events of neurogenesis: adhesion and migration of neuronal cells, orientation of growth of neurites and axons myelination. Functions of contactins are actively studied using model animals that express contactins in central and peripheral nervous system with almost similar to human pattern. Mutations of contactin-encoding genes result in abnormalities of neurogenesis process and development of multiple neurological disorders. Review is devoted to the role of contactin proteins in neurogenesis and nervous system disorders. PMID- 26995963 TI - [ALPHA-ACTININS AND SIGNAL TRANSDUCTION PATHWAYS]. AB - Involvement of actin cytoskeleton proteins in signal transduction from cell surface to the nucleus, including regulation of transcription factors activity, has now been supported by a lot of experimental data. Here-with, cytoskeletal proteins may have different functions than ones they execute in the cytoplasm. Particularly, alpha-actinin 4 stabilizing actin microfilaments in the cytoplasm can translocate to the nucleus and change the activity of several transcription factors. Despite the lack of nuclear import signal and DNA binding domain, alpha actinin 4 can bind to promoter sequences, and co-activate NF-kappaB-dependent transcription. Selective regulation of NF-kappaB gene targets may indicate involvement of alpha-actinin 4 in determining the specificity of cell response to NF-kappaB activation in cells of different types. PMID- 26995964 TI - [THE EFFECT OF PLAKOPHILIN-2 GENE MUTATIONS ON ACTIVITY OF THE CANONICAL Wnt SIGNALING PATHWAY]. AB - Plakophilin-2 is a desmosomal protein encoded by PKP2 gene. Desmosomal proteins are usually considered as structural proteins with the main function of maintaining intercellular interactions. Genetic studies revealed that mutations in desmosomal genes could lead to arrhythmogenic right ventricular cardiomyopathy, heart disease characterized by substitution of cardiomyocytes by adipose and fibrotic tissue predominantly in right ventricle. Wnt signaling pathway is one of the signal transduction pathways which could be involved in the formation of the pathology. The purpose of this study was to investigate Wnt activity changes caused by PKP2 mutations during adipogenic and cardiomyogenic differentiation. We used multipotent mesenchymal stromal cells and iPS cells generated from patient carrying PKP2 gene mutation. We show that Wnt activity is lower in the cells with mutant PKP2. This data indicate a possible signaling role of plakophilin-2 by regulating Wnt activity. PMID- 26995965 TI - [TUMOR SUPPRESSOR p63 REGULATES EXPRESSION OF UBIQUITIN LIGASE Pirh2]. AB - Transcription factor p63 is a member of the p53 protein family. Due to the high degree of structural similarity p53, p63, and p73 are known to have overlapping functions relating to cell cycle regulation, apoptosis and tumor transformation. Furthermore, p63 plays crucial role in epidermal tissue development and differentiation. Pirh2 (product of RCHY1 gene) is an E3 ubiquitin ligase modifying all three members of the p53 family resulting in their subsequent proteasomal degradation. Our results demonstrate that p63, similar to p53, is able to regulate expression levels of Pirh2. Importantly, Pirh2 expression is activated only by transcriptionally active isoform of p63--TAp63, but not the N terminally truncated DeltaNp63. PMID- 26995966 TI - [INDUCTION OF DECIDUAL DIFFERENTIATION OF ENDOMETRIAL MESENCHYMAL STEM CELLS]. AB - In this study, we compared the ability of human mesenchymal stem cells derived from menstrual blood (eMSCs) and mesenchymal stem cells (MSCs) from other tissues to differentiate into decidual cells in vitro. It was demonstrated that during differentiation secretion of decidualization markers (prolactin and insulin-like growth factor binding protein-1) increases in eMSCs from adipose tissue (MSC-AD). Thus, the ability of eMSCs to differentiate into decidual cells is much higher than MSC-BM or MSC-AD. It makes eMSCs promising for application in cellular therapy of infertility associated with decidualzation insufficiency. PMID- 26995967 TI - [STEM CELLS PLAY NO CONSIDERABLE ROLE IN CARDIOMYOCYTE REPOPULATION OF ADULT HUMAN HEART]. AB - There are two viewpoints concerning cardiac regeneration. One assumes that the myocardium of an adult human heart has a weak regenerative capacity. According to another, myocardium can renew at a high rate due to the presence of resident stem cells. This study was aimed to test the role of stem cells in myocardium repopulation in adult humans of different age by examining the distribution of cardiomyocytes as to their size and ploidy. Cytofluorimetry and interferometry were used to determine the dry weight, volume and ploidy of myocytes isolated from the left ventricle of the normal heart of 12 men aged 20-30 years (n = 7) and 40-50 years (n = 5). Dry weight of cardiomyocytes made up 6906 +/- 182 pg (10(-12) g) aged 20-30 years and 9126 +/- 263 pg in men aged 40-50 years. There were no cells with an intermediate volume between amplifying and mature myocytes. The number of candiomyocytes in the left ventricle made up (3.18 +/- 0.05) x 10(9) cells in the age group 20-30 years and (2.06 +/- 0.6) x 10(9) cells in the age group 40-50 years. Most of the myocyte population was represented by mononucleate cells with tetraploid nuclei (41.3%). Proportion of myocytes of different ploidy classes did not change in the interval from 20 to 50 years. Our results strongly suggest that stem cells of the heart are not involved in the regeneration of human myocardium during aging. The function of the aging heart is mostly compensated by the hypertrophy of the remaining myocytes. PMID- 26995968 TI - [THE STUDY OF THE ORIGIN OF HUMAN GLIOMA BASED ON CELL LINES AND TUMOR SPECIMENS]. AB - The present study is dedicated to the search of human glioma "cells of origin". Specimens of the tumor tissue have been analyzed via the RT-PCR method to potentially reveal the expression of molecular markers characteristic of various cells of nerve tissue (NeuN, MOG, MBP, NG2, Olig2, Vimentin, GFAP, AldhlL1), as well as markers of stem (Oct4, c-Kit) and cancerous stem (CD133) cells. We have shown that the expression profiles of these markers for different types of gliomas intersect, which does not allow to determine the type of "cells of origin". So, in order to study the origin of glioma using cell lines derived from primary cultures, we need a more sophisticated culture conditions, rather than the commonly used serum-based media. PMID- 26995969 TI - [PAIRWISE CROSS-SPECIES TRANSCRIPTOME ANALYSIS OF POLYPLOIDY-ASSOCIATED EXPRESSION CHANGES OF DEVELOPMENTAL GENE MODULES]. AB - Design and development of highly sensitive method bioinformatics are important for investigation of casual relationships between epigenetic changes and gene activity. Cell polyploidy may trigger such changes. However, maintaining the balance of gene dosage, polyploidy may provide only a rather weak effect on their expression. Currently, there is no comprehensive and concordant data in regard to ploidy-associated transcriptomic changes. To find out how polypoidy affects gene activity, we have developed an integrative bioinformatic method of pairwise cross species transcriptome analysis of mammalian tissues with various polyploidy degrees. The main benefit of this approach is its ability to separate species- and tissue-specific noises of evolutionary conserved effects. We demonstrat the application of the method for the analysis of gene modules and protein interactions networks coordinating programs of development, differentiation and pluripotency. The analysis was performed with transcriptomes of polyploid and diploid organs (human and mouse heart and liver). Our data indicate that ploidy induced genes enrich Gene Ontology (GO) biological processes and KEGG pathways related to development, morphogenesis and stem cells biology (including Hippo, Pi3K, WNT, Hedgehog and TGF-beta pathways) with higher degree than ploidy inhibited genes. Thas, our data are the first to show that polyploidy may induce and coordinate developmental modules. PMID- 26995970 TI - [DUAL PROAPOPTOTIC AND PRONECROTIC EFFECT OF HYDROGEN PEROXIDE ON HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS]. AB - The ratio of early apoptosis and late apoptosis (necrosis) in the cultured human umbilical vein endothelial cells was estimated after exposure to hydrogen peroxide (H2O2) in vitro trying to keep them close to the physiological conditions (high cell density, high serum content, H2O2 concentration not over 500 MUM). Cell viability was assessed using flow cytometry and simultaneous staining with fluorescent dyes PO-PRO-1 to detect early apoptotic cells, and DRAQ7 to detect late apoptotic and necrotic cells. The data obtained suggest that the primary mechanism of cytotoxic response is apoptosis. The critical concentration of H2O2 causing the death of the cell population in a dense monolayer is 250 MUM. Lower concentrations of H2O2 (up to 200 MUM) cause death of individual cells; however, viability of endothelial cell population is retained, and response to calcium activating agonists does not change compared with control cells. PMID- 26995971 TI - [PROTEOMIC ANALYSIS OF ADAPTIVE MECHANISMS TO SALINITY STRESS IN MARINE GASTROPODS LITTORINA SAXATILIS]. AB - Salinity is one of the most important abiotic environmental factors affecting marine animals. If salinity deviate from optimum, adaptive mechanisms switch on to maintain organism's physiological activity. In this study, the reaction of the snails Littorina saxatilis from natural habitats and in response to experimental salinity decreasing was analyzed on proteomic level. The isolation of all snails inside their shells and gradually declining mortality was observed under acute experimental salinity decrease (down to 10 per hundred). Proteomic changes were evaluated in the surviving experimental mollusks compared to control individual using differential 2D gel-electrophoresis (DIGE) and subsequent LC-MS/MS identification of proteins. Approximately 10% of analyzed proteins underwent up- or down regulation during the experiment. Proteins of folding, antioxidant response, intercellular matrix, cell adhesion, cell signaling and metabolic enzymes were identified among them. Proteome changes observed in experimental hypoosmotic stress partially reproduced in the proteomes of mollusks that live in conditions of natural freshening (estuaries). Possible mechanisms involved in the adaptation process of L. saxatilis individuals to hypo-osmotic stress are discussed. PMID- 26995972 TI - [Laparoscopic surgery for rectal cancer: a literature review and own experience]. AB - The main treatment option for rectal cancer is surgery, which "gold standard" is the total mesorectumectomy. There are presented literature review and the results of own research devoted to comparative analysis of outcomes of laparoscopic and open total mesorectumectomy. Current data and own experience show the oncological adequacy and safety of laparoscopic approach however the controversy of some results reveal the necessity of further investigation. PMID- 26995973 TI - [Role of T- and B-cell immunity in the pathogenesis of cancer]. AB - Adaptive immunity plays a crucial role in the system of anti-tumor defense of the organism. The theory of immune surveillance defines the presence of permanent monitoring of the organism for the detection of malignant transformed cells and their elimination or suppression of the growth. However in some cases tumor cells overcome immune surveillance that leads to the development of cancer. PMID- 26995974 TI - [Predicting of the effectiveness of radiotherapy and chemoradiotherapy for cancer patients]. AB - Studies carried out on samples of tumor and non-tumor tissue indicate that markers of radiosensitivity for predicting individual patient response to the planned radiation therapy may be the indicators of apoptosis and molecular profiles read from the DNA of patients. At present there is developed a technology for rapid and economical determining of indicators for the reasonable use of radiation therapy in the radiological practice in patients with breast cancer, bladder cancer and malignant glioblastomas by means of an evaluation of radiosensitivity of the DNA of blood. PMID- 26995976 TI - [Endoglin (CD105)--a target for visualization and anti-angiogenic therapy for malignant tumors]. AB - Drugs currently used for anti-angiogenic therapy which are based on monoclonal antibodies to VEGF and its receptors are of limited efficiency. Endoglin (CD105) is a protein receptor of TGF-beta superfamily involved in ligand binding and signal transduction regulating VEGF-independent mechanisms of angiogenesis. CD105 is highly expressed on membranes of endothelial cells of vessels in growing tumors. It plays a crucial role in determination the state of activation or quiescence of endotheliocytes. CD105 is present also on membranes of tumor stromal cells (macrophages, fibroblasts, pericytes). High density of CD105 positive microvessels in tumors corresponds with its aggressivness, spreading to regional lymph nodes and poor prognosis. In patients with progressing tumors soluble form of endoglin in peripheral blood may be detected. Monoclonal antibodies to CD105 and their derivatives are regarded as a basis for creation of new generation of anti-angiogenic reagents for visualization of tumor vessels, for direct effect on endothelium or for targeted drugs delivery to growing tumors. PMID- 26995975 TI - [Molecular biology of familial cases of human melanoma]. AB - Skin melanoma is an etiologically heterogeneous disease, the development of which is related to a complex interaction of environmental factors and individual genetic characteristics. This article provides current molecular-genetic aspects of familial cases of melanoma and polymorphism of genes directly related to the risk of developing this hereditary disease. The studies of hereditary cancer cases add our knowledge of mechanisms oncotransformation, genetic changes in signaling pathways, which are responsible for invasiveness, metastasis and drug resistance of melanoma cells of the skin. PMID- 26995977 TI - [Diagnosis and treatment for Paget's breast cancer: state of the art]. AB - Breast cancer is the most common cancer in women. According to WHO experts in the world each year there are revealed from 800,000 up to 1 million new cases of breast cancer. In the structure of malignant tumors morbidity among female population, in Russia in 2012 breast cancer ranked the first place (20.7%) and remained the leading malignant pathology in women. Paget's breast cancer is a rare form of breast cancer that occurs in the mouth of the excretory ducts of the nipple, which characterized by lesion of the nipple and large ducts, often with the formation of tumor in the breast. This rare abnormality occurs in 0.5-5% of all cases of breast cancer. PMID- 26995978 TI - [Automated identification, interpretation and classification of focal changes in the lungs on the images obtained at computed tomography for lung cancer screening]. AB - This review article analyzes data of literature devoted to the description, interpretation and classification of focal (nodal) changes in the lungs detected by computed tomography of the chest cavity. There are discussed possible criteria for determining the most likely of their character--primary and metastatic tumor processes, inflammation, scarring, and autoimmune changes, tuberculosis and others. Identification of the most characteristic, reliable and statistically significant evidences of a variety of pathological processes in the lungs including the use of modern computer-aided detection and diagnosis of sites will optimize the diagnostic measures and ensure processing of a large volume of medical data in a short time. PMID- 26995980 TI - [Comparative clinical analysis of histological systems of adrenocortical tumors diagnosis]. AB - Differential diagnosis of adrenocortical cancer (ACC) and cortical adenoma presents certain difficulties since there is no specific histological criterion allowing to distinguish tumors of the adrenal cortex with malignant clinical course. Currently there are offered several systems, and the most widely spread have the index Weiss (IW) and the modified index Weiss (MIW). The accuracy of one or another of the proposed systems remains a matter of debate. There was analyzed own experience on the use of IW and MIW in the diagnosis of 91 cases of the ACC and 13 cases of cortex adenomas of the size at least 5 cm. For the diagnosis of large adenomas sensitivity IW was 77%, MIW--100%. For the diagnosis of metastatic and non-metastatic ACC--100% and 97%, 100% and 86%, respectively (p > 0.05). In multivariate analysis of life expectancy of patients the definition of IW and MIW had a prognostic significance. MIW was less subjective, more simple and convenient to be used and it showed a great informative value at the reclassification of certain "adenomas" into ACC. However to use it on their own, without IW, was impractical as MIW had wider gray area and did not reach the threshold value in some cases of ACC. For the diagnosis of tumors of the adrenal cortex IW remains a standard; when a value was equal of 2 or in cases of doubt it was necessary to calculate MIW as well. PMID- 26995979 TI - [Cancer mortality in the Altai Republic]. AB - Cancer mortality rate in the Altai Republic is the lowest among the territories of the Siberian Federal District. Cancer mortality rate in females is 1.9 times lower than that in males. From 2003 to 2012 cancer mortality rate ranged within the confidence interval. Men most often die from tumors localized in the respiratory and digestive systems and women--from tumors of the reproductive and digestive systems. Age-standardized incidence rates are significantly higher in urban males and females than in rural population (p < 0.05). Mortality from lung, liver and kidney cancers is higher for urban than for rural males. For urban females, mortality from breast, stomach and rectum cancers is higher than for rural females. Rural women die of esophageal cancer more often than urban women. Risk to die of cancer in 2012 was 23.6% (33.9% for males and 18.9% for females) being higher in urban than in rural population. PMID- 26995981 TI - [Melphalan pharmacokinetics during isolated limb regional perfusion in patients with skin melanoma and soft tissue sarcoma]. AB - The study of pharmacokinetics of melphalan in the perfusate and blood plasma during isolated limb regional perfusion (ILRP) was carried out in patients with melanoma (n=21) and soft tissue sarcoma (n = 24). Melphalan was administered as 10 mg/l for a lower extremity and 13 mg/l for a upper extremity. Quantification of melphalan in perfusate and blood samples was performed by means of liquid chromatography/tandem mass spectrometry. 30 samples of the perfusate and 27 venous blood samples were analyzed. During the first 5 minutes of ILRP concentration of melphalan in the perfusate decreased to 13.2% of the initial value, and by the end of perfusion (60 minutes) it was 3.3%. The amount of melphalan in the blood plasma of the patients by the end of ILRP wasn't higher than 1.6% from the administered dose. That demonstrates minor systemic absorption of the drug during ILRP. Moreover melphalan concentration in the blood plasma during the perfusion was in average 0.015-0.223 mg/l which is significantly lower compared to the blood plasma concentrations after intravenous administration of melphalan. Thus ILRP procedure provided 97% of the melphalan dose accumulation in the soft tissues of a limb and in tumor tissues. Also pharmacokinetic advantage of melphalan over systemic administration of the drug was shown. PMID- 26995982 TI - [Comparative analysis of immediate results of surgery for colon cancer using laparoscopic and robot-assisted surgical interventions]. AB - In recent decades there has been achieved significant progress in treatment for colorectal cancer. Minimally invasive surgery (including robot-assisted) is rapidly gaining widespread acceptance in treatment of this form of cancer. Today robotic surgery is a revolutionary technology that opens a new stage in the development of surgery of the 21st century. Currently in the world there have been performed more than 2 million surgical interventions of the colon using a robotic surgical complex Da Vinci. To date it was accumulated a large number of single-center studies comparing laparoscopic and robot-assisted interventions in cancer of various parts of the colon for short-term and long-term treatment outcomes, which showed their effectiveness and safety. Modern colorectal surgery could not be imagined without the latest technology, the use of which directly affects the quality of life of patients after surgery. PMID- 26995983 TI - [Association of the Arg399Gln polymorphisms of the XRCC1 gene with breast cancer risk in Kyrgiz women]. AB - There were examined 219 women of Kyrgyz nationality (mean age 51 +/- 9.7 years). 117 female with breast cancer (BC) and 102 apparently health controls. The diagnosis of breast cancer was confirmed histologically. DNA was prepared from whole blood samples. XRCC1 genotypes Arg399Gln were examined using polymerase chain reaction-restriction enzyme polymorphism (PCR-RFLP). The frequency of the variant 399Gln allele and heterozygous genotype Arg399Gln of the Arg399Gln polymorphism of the XRCC1 gene were significantly higher among women with breast cancer compared with control subjects (p < 0.05). The Arg399Gln polymorphism of the XRCC1 gene is associated with breast cancer risk in a Kyrgyz women when using additive model (chi2 = 4,901; p = 0.0268) general model (chi2 = 13,86; p = 0.0010) and dominant model of inheritance (chi2 = 11.18; p = 0.0008). Women having the 399Gln allele had 1,57 fold (95% CI 1.7-2.30; p = 0.002) higher risk of developing BC compared with subjects carrying neither of these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2.77 fold (95% CI 1.6-4, p = 0.002) higher risk of BC. Thus, the heterozygous genotype Arg399Gln and 399Gln allele of XRCClgene are associated with an increased risk of breast cancer in Kyrgyz females. PMID- 26995984 TI - [Differential expression beta2 and beta4 isoforms of retinoic acid receptor gene RARbeta as possible prognostic factor in multiple myeloma]. AB - In this study, for the first time the expression of beta2 and beta4 isoforms of RARbeta gene was investigated in group of 19 patients with the newly diagnosed multiple myeloma. The expression of both RARbeta2 and RARbeta4 isoforms was detected in all patients, but it was different and had opposite tendency. We showed that RARbeta4 expression level positively correlated with VEGF-A and VEGFR1 expression levels. It was found that higher levels of RARbeta4/VEGF A/VEGFR1 co-expression were defined of patients with statistically significant increase of plasma cell level and paraprotein concentration. The median overall survival was lower in patients with RARbeta4, over-expression, while the maximal median overall survival was observed of patients with RARbeta2 down-regulation and nearly absolute RARbeta4inactivation. PMID- 26995985 TI - [Diagnosis and treatment strategy of malignant pleural effusions in outpatient conditions]. AB - According to results of the study, which included 52 patients with malignant pleural effusion of unknown etiology, it could be concluded that the method of choice in differential diagnosis of pleural effusion is the immunocytochemistry as the most informative method (efficacy 94,2%). Based on own experience of treatment of 137 patients with recurrent malignant pleural effusions, we can say that the first stage of treatment of pleural effusions is carrying out pleurodesis in outpatient conditions. The choice of pleurodesis method, first of all, depends on the aggressiveness of tumor pleurisy: in a case of daily exudation till 300 ml we choose talc pleurodesis, from 300 to 700--bleomycin pleurodesis, more than 700--combined (talc and bleomycin pleurodesis). The overall efficiency of produced pleurodesis is 64.5%. PMID- 26995986 TI - [The results of combined treatment of patients with locally advanced laryngeal cancer using preoperative chemoradiotherapy]. AB - The combined treatment with preoperative chemoradiotherapy (CRT) was performed in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) was carried out according to the scheme "1 + 1 Gy" (interval 4-5 hours) 5 times a week till 30-40 Gy. RT was accompanied by simultaneous polychemotherapy: vincristine (1.4 mg/m2 per day), cisplatin (20 mg/m2--2-4 days) bleomicetin (10 mg/ m2--5, 6 days), cyclophosphamide (200 mg/m2--7, 8 days). Surgical treatment was carried out in 2.5-3 weeks after CRT. CRT allowed conducting organ-saving surgery on the larynx in 11 (52%) of 21 patients with T3 of primary tumor. All other patients underwent laryngectomy at a different volume. Five-year disease-free survival for the whole group in total (T3-4) was 88%. Relapses of regional metastases (MTS) occurred in 7 of 9 patients including in 4 of 5 patients after lymphadenectomy. The overall survival of patients with T3N02 was 71%, with T4N0-3--20%. Thus we have developed a method of treatment allowing to achieve high local relapse-free survival in patients with locally advanced laryngeal cancer. However organ-saving effectiveness of preoperative CRT and its effect on regional MTS remain low, which requires further research in this direction. PMID- 26995987 TI - [Immediate results of isolated chemoperfusion of the lung with melphalan and cisplatin in combination with metastasectomy in treatment for resectable metastatic lung lesions]. AB - For treatment of metastatic lung lesions there was used the method of isolated chemoperfusion in combination with metastasectomy. The study included 74 patients (mean age 43 +/- 13.4 years). There were performed 99 normothermic isolated chemoperfusions of the lung: with melphalan (39) and cisplatin (60). During surgery there were no lethality outcomes. In the immediate postoperative period it was recorded 1 (1.4%) death developed in 3 days after surgery. The cause of this death was postperfusion lung edema accompanied by increase of signs of respiratory insufficiency. There were following complications after isolated chemoperfusions of the lung: anemia--23 (23.1%), nausea--13 (13.1%), vomiting--5 (5.1%), atrial fibrillation--10 (10.1%), pneumonia-2 (2.0%), pulmonary infarction -2 (2.0%), chylothorax--1 (1.0%), pneumothorax--29 (29.3%), emphysema of soft tissues of the chest wall 73 (73.7% ). Thus isolated chemoperfusion of the lung with melphalan or cisplatin is a procedure reproducible and relatively safe. PMID- 26995988 TI - [Complex treatment of breast cancer patients with brain metastases]. AB - Brain metastases in breast cancer develop for 24-32 months after the detection of the primary tumor. The study included patients with brain metastases who were divided into three groups: the first group--with early chemoradiotherapy (CRT) without induction chemotherapy (IC) by capecitabine; the second group--with delayed CRT with 4 or 8 courses of IC by capecitabine; the third group (a historical control) who received only whole brain radiation therapy. The median time to progression of intracranial metastases was 15.3, 12 and 5 months, respectively. The median time to the intracranial progression significantly less in the third group (5 months) compared with the first (15.3 months) (p = 0.0007) and the second (12 months) (p = 0.027) groups. The overall survival rate was 22.1, 15.1 and 6.8 months in three groups, respectively. PMID- 26995989 TI - [Assessment of applicability of archived cytological lung cancer specimens for molecular genetic analysis]. AB - Molecular genetic analysis of lung tumors is often essential for the proper choice of therapy. EGFR mutation is a well-known marker of sensitivity to gefitinib, erlotinib and afatinib; ALK-translocations make tumor sensitive to several ALK inhibitors; low intratumoral expression of DNA repair genes (ERCC1, BRCA1, etc.) may increase the therapeutic index of platinum-based drugs. Usually these markers are evaluated using formalin-fixed paraffin-embedded tumor tissues. The goal of this work was to assess utility of archived cytological lung cancer specimens as an alternative source of material for molecular genetic testing. We analyzed paired histological and cytological lung adenocarcinoma specimens. Comparison of results within the pairs showed that cytological material can be used instead of histological material for qualitative analyses (detection of EGFR mutations or ALK-translocations); however, gene expression measurements, obtained by quantitative real-time PCR, may differ significantly in histological and cytological samples from the same patient. PMID- 26995990 TI - [Quality of life and socio-medical consequences in adolescent and young adult survivors following treatment for Hodgkin's lymphoma]. AB - Between 1997 and 2008, 97 adolescents and young adults with a median age 18.9 years (range, 15.0-33.6) with all stages Hodgkin's lymphoma (HL) were treated by a pediatric protocol DAL-HD-90m. The 12-year event-free survival and overall survival was 73.4 +/- 4.8% and 81.5 +/- 4.7% respec- tively. The frequency of secondary malignancies was 2.1%. In the study of quality of life (QOL), 47 patients were included with duration of complete remission at least 5 years who had no relapses and other adverse events. The median age of the patients at the time of testing was 28.0 years (range, 23.2- 41.0). Reference values of age adjusted 85 healthy volunteers were used for comparison. The QOL was measured through the questionnaire EORTC QLQ-C30. In total, the QOL of survivors was comparable to that of our control and reference values of EORTC. The only factor that influenced the QOL of long-term survivors was the presence or absence of their children. Among patients who did not have their own children was increased activity of the fatigue (+14.4 points; p = 0.035), insomnia (+25; p = 0.003) and anorexia (+16.7; p = 0.009). The deficit on the overall QOL score was -14.6 points (p = 0.005). PMID- 26995991 TI - [Surgery for cardio-esophageal cancer]. AB - The experience of surgery of 369 patients with cardio-esophageal cancer treated in the Kazan Republic Clinical Oncology Center is presented. The patients are divided into 3 groups respective of the type of adenocarcinoma (classification by J.R. Siewert). Thus, the first group consists of 45 (12.1%) patients, the second- 172 (46.6%) and the third--152 (41.3%) patients. Each group is divided into subgroups according to the performed operation: transhiatal esophagoplasty with esophagogastroanastomosis on the neck, transthoracal esophagoplasty (operations by Lewis and Gerlock) with intrapleural esophadogastroanastomosis and gastrectomies with high resection of esophagus. High productivity of the differentiated approach to surgical treatment of cardio-esophageal cancer depending on the type of adenocarcinoma is shown. Such approach allows the surgical treatment to be more radical, to reduce quantity of the early and remote complications and to raise the survival. So, it is revealed that performance of transhiatal and transthoracal esophagoplasty is possible in cases of type I adenocarcinoma. Gastrectomies in cases of type II adenocarcimoma are of poor prognosis. PMID- 26995992 TI - [Evaluation of survival of prostate cancer patients after transurethral resection of the prostate]. AB - The study included 164 prostate cancer patients with a history of acute or chronic urinary retention. Conservative therapy or transurethral resection of the prostate were carried out to all patients as treatment for urinary retention. There was studied an influence of transurethral resection of the prostate on the survival of patients with prostate cancer and development of radiation complications following radiotherapy. Overall survival of prostate cancer patients who underwent transurethral resection of the prostate was significantly higher than in patients who had only conservative therapy as a treatment of dysuria. The frequency of radiation complications was lower in patients who had transurethral resection of the prostate prior radiation therapy. PMID- 26995993 TI - [Evaluation of diagnostic effectiveness of the method of diffusion-weighted MR images in diagnosis of pathology of the uterine body]. AB - The purpose of this study was to evaluate diagnostic efficiency of methods of diffusion-weighted imaging (DWI) in the diagnosis of diseases of the body the uterus at the high and ultra high field MRI (1,5T1, 3,OT1). In total we examined 150 patients. In 72 patients (48%) there were histologically verified malignant changes; of these 70 patients (46.7%) had endome- trial cancer (EC), 2 (1.3%)- uterine sarcoma. 40 EC patients (57.2%) had of Stage I, 15 patients (21.4%)- Stage II, 11 patients (15.7%)--Stage III, and 4 patients (5.8%) of--stage IV. 48 patients (32%) had benign processes of the endometrium (uterine fibroids--27 patients, endometrial hyperplasia--12 patients, endometrial polyps--9 patients). The control group consisted of 30 (20%) healthy patients. All patients underwent MRI examination of the pelvic organs into high and ultra-high MRI (1,5T1, 3,0T1). All patients were required performance of SP DWI (diffusion-weighted images) in 2 projections (Ax and Sag) with different diffusion factors (50-500-1100). MRI data using DWI were compared with surgical material. To our opinion modern MRI techniques allow to reliably determine the size of the pathological process, its location, the extent of the parameters for endometrial cancer, as well as the degree of involvement in the pathological process of the bladder and rectum, to assess the condition of the pelvic lymph nodes. MRI, supplemented DWI, allowed differentiating benign and malignant lesions of the uterus. MRI data corresponded to a post mortem conclusion in the case, specificity 86%, sensitivity of 92% and a diagnostic accuracy of 91%, which significantly improved the diagnostic accuracy of a standard MRI. Thus the method DWI MRI using modern software improves the differential diagnosis of diseases of the body uterus, can reliably assess the extent of the pathological process, to fully assess the invasion of parametrial tissue, provide a comprehensive assessment of the status of the lymph nodes. PMID- 26995994 TI - [Colorectal cancer screening based on quantitative determining of fecal hemoglobin and transferrin]. AB - To reduce mortality rate from cancer there has been developed a program of colorectal cancer screening. It was conducted a pilot implementation of the methodology of colorectal cancer screening based on quantitative immunochemical determination of fecal hemoglobin and transferrin with colonoscopy. The study included 10307 men and women aged 50 years and older without symptoms of the disease who received containers for a 2-day collection of stool samples. There were returned 9455 sets with samples (91.8%). Of these an excess hemoglobin level and/or transferrin above the threshold was in 1354 (14.3%). 1164 patients (86% of positive) underwent colonoscopy. Colon diseases were found in 662 patients including polyps in 237. The efficiency of a 2-day test to detect polyps was significantly higher compared to a 1-day. Colorectal cancer was revealed in 23 people--2.4 per 1000 patients. 87% of patients had cancer of stages I and II, 13% -in stage III. The results of the introduction of screening program confirm the possibility of its use in practical public health. PMID- 26995996 TI - [Spontaneous cytotoxicity treated with anti-tumor drugs of splenocytes of rats on a model of hepatoma cell monolayer cultures]. AB - A purpose of this research is the study of spontaneous cytotoxic activity of effector cells (EC) of the innate immunity of animals against target cells (TC) of cultured hepatoma. There are established differences in the cytotoxic potential of freshly non-activated mouse and rat splenocytes: TC exhibit resistance to splenocytes of mice C3HA and are exposed to active dose-dependent killing under the influence of splenocytes outbred rats. There were revealed two mechanisms of killing of clip-target by splenocytes of rats--secretory variant (Zajdel hepatoma) and the path of classical apoptosis (hepatomas HTC, MH-22a and BWTG3). Single intraperitoneal administration of anticancer drugs cyclophosphamide (CP) and 5-fluorouracil (5-FU) to animals inhibits secretory pathway, whereas the activity of the apoptotic mechanism is enhanced after administration of CF to animals and is unchanged under the action of 5-FU. PMID- 26995995 TI - [Possibilities of transanal endoscopic microsurgery: the experience of 202 operations]. AB - Transanal endoscopic microsurgery (TEM/TEO) is a standard treatment for rectal adenomas but can also be used for selected malignant tumors. Rectal adenomas, selected adenocarcinomas and carcinoids were chosen for operations. Preoperative work-up included: digital rectal examination, rectoscopy with biopsy, colonoscopy, EUS, pelvic CT (MRI). Two hundred and two patients [mean age of 62.4 +/- 10.3 (33-86)] had TEO. The mean size +/- SD of tumors was 3.2 +/- 1.4 cm (0.6 8.0). Mean distance from anal verge and dental line was 7.1 +/- 2.4 cm (2.5-14.0) and 4.6 +/- 2.6 cm (0.5-12.0), respectively. Preoperative biopsy revealed: adenoma--156/202 (77.2%), adenocarcinoma--39/202 (19.3%) and carcinoid--7/202 (3.5%). The median operating time was 40 (20-180) min. Tumor-free margins were obtained in 200/202 (99%) operative specimens, 2/202 (1.0%) cases tumors were fragmented. Morbidity was 7/202 (3.5%). Pathological investigation revealed: adenoma in 109/202 (54.0%) cases, adenocarcinoma stage Tis, T1, T2 and T3 in 86/202 (42.5%), carcinoid in 5/202 (2.5%), neurilemoma in 1/202 (0.5%), neurofibroma in 1/202 (0.5%). One hundred and two patients had follow-up (95%). Median follow-up at 20 (1-41) months; 3/192 patients with adenocarcinoma, 1/192 patient with adenoma and 1/192 patient with carcinoid had local recurrence. Thus, transanal endoscopic microsurgery for rectal adenomas and selected malignant tumors is associated with low morbidity and low recurrents rates. PMID- 26995997 TI - [New method of plastic in surgery for skin melanoma localized near body's midline]. AB - With a wide excision of skin melanoma localized in areas of the sternum, the sacrum or on the back near body's midline there is often occurred a problem of closing appeared defect. Local tissues are insufficient and performing of free plastic is undesirable because of the unfavorable conditions of the free flap engraftment due to the peculiarities of transplant bed and difficulties of immobilization and fixation of the flap. For exactly such surgical situations we have developed a method of reliable replacement of appeared defects by two adjacent symmetrical rotary flaps. PMID- 26995998 TI - [Combination of pegfilgrastim and plerixafor as an effective regimen of hematopoietic stem cells mobilization in cancer patients: own experience]. AB - The method of high-dose chemotherapy is limited quantity and quality of hematopoietic material used in transplantation. In this article on own material (56 apheresis procedures) there was performed a comparative analysis of the efficacy of several mobilization regimens. In 35 patients (63%) apheresis was initiated with using DHAP ([D]examethasone; [H]igh-dose [A] ra-C; [P]latinol) + G CSF (group No 1); in 9 patients (16%) apheresis was initiated with regimen of HDCyc ([H]igh [D] ose [Cyc]lophosphamide) + G-CSF (group No 2); in 12 patients (21%) apheresis was performed using a combination of plerixafor and pegfilgrastim (group No 3). It was shown that all three of the proposed regimens were found to be as effective. In all groups, patients failed to receive an enough amount of CD34 + cells. At the same time using new mobilizing agent plerixafor in combination with prolonged action G-CSF pegfilgrastim showed some advantages: low toxicity of this combination, which does not needs to additional blood components, antibacterial and antifungal agents, and the possibility of its use in the outpatient setting. PMID- 26996000 TI - [Early detection of cancer--genetics or immunology?]. AB - The earliest (in preclinical stages) detection of malignant tumor process is a key factor in successful treatment of cancer. What methods and approaches are most suitable for this purpose? The paper presents current understanding of the biological basis of the process of malignancy and analyzes the comparative opportunities and prospects for early detection of cancer using molecular genetics and immunochemical approaches. PMID- 26995999 TI - [Molecular-biological subtypes of breast cancer in the Republic of Uzbekistan]. AB - An interest to the heterogeneity of breast cancer (BC) is not being quenched. At the present stage of clinical oncology treatment of breast cancer is based not only on the "classic" data as stage of disease, grade, histology but molecular biological characteristics studied in different populations. In the Republic of Uzbekistan these characteristics of breast cancer are published in fragments, which was the purpose of carrying out a large-scale study to obtain reliable comprehensive data on the issue. PMID- 26996001 TI - [75h birthday of D. G. Zaridze]. PMID- 26996002 TI - [Memory of R.I. Wagner]. PMID- 26996003 TI - Chemical Constituents and LC-profile of Fresh Formosan Lonicera japonica Flower Buds. AB - One new secoiridoid glucoside, ethylsecologanin dimethyl acetal (1), along with 15 known compounds, comprising six iridoid glucosides (2-7), six flavonoids (8 13), two sterol glucosides (14 and 15), and chlorogenic acid (16) were isolated from the flower buds of Formosan Lonicera japonica. The structures of these isolates were determined on the basis of mass and spectroscopic analyzes. In addition, the chemical profiles of fresh Formosan honeysuckle buds and the dried Chinese one were compared by HPLC with a PDA detector. The calibration curve of the active component, chlorogenic acid, was also provided. As a result of the constituent similarity, Formosan L.japonica can be an alternative to the Chinese honeysuckles. PMID- 26996004 TI - Isolation and Characterization of Sclerienone C from Scleria striatinux. AB - Herein, we report the isolation and characterization of sclerienone C, a novel sesquiterpene isolated from the methylene chloride/methanol (1:1) extract of Scleria striatinux that we have deduced to have structure 1. This medicinal spice of Cameroon has been shown to display antimicrobial and antiplasmodial activities. The isolation and purification involved a combination of methods including silica gel column chromatography, Sephadex LH-20, and semi-prep HPLC separations. Structure elucidation was carried-out by means of spectroscopic analysis and comparison with previously isolated sesquiterpene derivatives from the plant. PMID- 26996005 TI - Cytotoxic and Pro-apoptotic Activities of Sesquiterpene Lactones from Inula britannica. AB - In this study, five known sesquiterpene lactones (STL) with an alpha-methylene gamma-lactone motif, including two eudesmanolides, 1beta-hydroxyalantolactone (1) and ivangustin (2), and three 1,10-seco-eudesmanolides, 1-O-acetylbritannilactone (3), 1,6-O,O-diacetylbritannilactone (4), and 6alpha-O-(2- methylbutyryl)britannilactone (5) were isolated from the flower heads of the medicinal plant Inula britannica. Their structures were characterized by spectroscopic methods. X-ray data of 2 is reported for the first time. Among them, eudesmanolides 1 and 2 exhibited remarkable cytotoxicity against HEp2, SGC 7901 and HCT116 human cancer cell lines, comparable with etoposide (Vp-16) used as reference drug. Furthermore, treatment of HEp2 cells with 1 induced apoptosis associated with cleaved procaspase-3 and PARP. The biological assays carried out with normal cells (CHO) revealed that all sesquiterpenes were weakly selective against the cancer cell lines tested. PMID- 26996006 TI - Influence of Merosesquiterpenoids from Marine Sponges on Seedling Root Growth of Agricultural Plants. AB - The impact of the merosesquiterpenoids avarol (1), avarone (2), 18 methylaminoavarone (3), melemeleone A (4), isospongiaquinone (5), ilimaquinone (6), and smenoquinone (7), isolated from marine sponges of the Dictyoceratida order, was studied on the root growth of seedlings of buckwheat (Fagopyrumesculentum Moench), wheat (Triticumaestivum L.), soy (Glycine max (L.) Merr.), and barley (Hordeumvulgare L.). Compounds 2and 6 were effective for the root growth of wheat seedlings, compound 3 stimulated the root growth of seedlings of buckwheat and soy, compound 4 affected the roots of barley seedlings, and compound 5 stimulated the root growth of seedlings of buckwheat and barley. Compounds 1 and 7 showed no activity on the root growth of the seedlings of any of the studied plants. The stimulatory effect depends on the chemical structure of the compounds and the type of crop plant. PMID- 26996007 TI - A New Cytotoxic Clerodane Diterpene from Casearia graveolens Twigs. AB - The first phytochemical investigation of Casearia graveolens twigs led to the isolation and identification of a new clerodane diterpene, caseariagraveolin (1), together with six known compounds (2-7). Their structures were elucidated by intensive analysis of their spectroscopic data. Compound 1 showed strong cytotoxicity against oral cavity and breast cancer cell lines with IC50 values of 2.48 and 6.63 uM, respectively. PMID- 26996009 TI - Trocheliolide B, a New Cembranoidal Diterpene from the Octocoral Sarcophyton trocheliophorum. AB - A new cembranoidal diterpene, trocheliolide B (1), was isolated from the octocoral Sarcophyton trocheliophorum. The structure of 1 was elucidated on the basis of spectroscopic methods. PMID- 26996008 TI - Influence of Tanshinone IIA on the Apoptosis of Human Esophageal Ec-109 Cells. AB - The induced-apoptosis effect and mechanism of human esophageal cancer Ec-109 cells via tanshinone IIA was investigated. The Ec-109 cells were cultured in vitro with different concentrations of tanshinone IIA (2 ug/mL, 4 ug/mL, or 8 ug/mL) for 12, 24, 36, and 48 hours. MTT assay was used to evaluate the proliferative inhibition rate of tanshinone IIA on esophageal Ec-109 cells. After 24 hours of culturing in vitro, a control group was assigned. The apoptosis rate was detected by the AO/EB and annexin V-FITC/propidium iodide assay, and the protein levels of Caspase-4 and CHOP were determined by the Western blot technique. MTT data showed that tanshinone IIA could significantly inhibit the proliferation of Ec-109 cells with a dose- and time-dependent mode. Compared with the control group, tanshinone IIA could apparently induce apoptosis of Ec-109 cells, and the level of Caspase-4 and CHOP (p < 0.01) obviously increased. Tanshinone IIA can significantly induce the apoptosis of Ec-109 cells, which may take effect by the stress pathway of the endoplasmic reticulum. PMID- 26996010 TI - Synthesis of a Novel 1,2,4-Oxadiazole Diterpene from the Oxime of the Methyl Ester of 1beta,13-Epoxydihydroquinopimaric Acid. AB - Oximation of the dihydroquinopimaric acid O-cyanoethylderivative (2) via the amidoxime 3, and cyclization with trifluoroacetic anhydride resulted in a new 1,2,4-oxadiazole diterpenoid (4). PMID- 26996011 TI - Phytochemical and Biological Investigations of Conradina canescens. AB - Conradina canescens (Lamiaceae) is an endemic evergreen shrub native to Florida, Mississippi and Alabama, with no phytochemical or biological studies registered in the literature. Thus, a phytochemical study and a toxicity analysis of the chloroform extract obtained from the leaves of C. canescens were performed for the first time. In our preliminary screening, the crude extract and its fractions were subjected to cytotoxicity, antimicrobial and antileishmanial bioassays. The crude extract showed substantial cytotoxic, antimicrobial and antileishmanial activities. A total of six compounds, namely ursolic acid (62.4%), betulin (8.4%), beta-amyrin (4.6%), myrtenic acid (2.9%), n-tetracosane (1.4%), and oleanolic acid (1.1%), were isolated. The structures of the isolated compounds were established by spectroscopic studies using NMR and IR spectroscopy. PMID- 26996012 TI - A New Taraxastane-type Triterpenoid from Cleistocalyx operculatus. AB - Ten known compounds including a chalcone, a long-chain alcohol, two flavonols, and six triterpenoids/steroids together with a new taraxastane-type triterpenoid, named cleistocalyxin, were isolated from the leaves of Cleistocalyx operculatus. The structure of cleistocalyxin was determined on the basis of IR, MS and NMR spectroscopic methods. PMID- 26996013 TI - Anti-allergic Inflammatory Triterpenoids Isolated from the Spikes of Prunella vulgaris. AB - Twelve known triterpenoids (1-12) and two steroids (13 and 14) have been isolated from the spike of the plant Prunella vulgaris. Among them, 2alpha,3alpha,23 trihydroxyursa-12,20(30)-dien-28-oic acid (10) was isolated for the first time from this plant. All isolates were evaluated for their inhibitory effect on the gene expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL 6), and release of histamine in human mast cells. beta-Amyrin (5), 10, and euscaphic acid (12) showed suppression of histamine release with percentage inhibitions of 46.7, 57.9, and 54.2%, respectively. In addition, 5 and 10 showed strong inhibition of TNF-alpha and IL-6 in the test for pro-inflammatory cytokines. Our results suggest that compounds 5 and 10 largely contribute to the anti-allergic inflammatory effect of P. vulgaris. PMID- 26996014 TI - Inhibition of Alpha-Glucosidase by Synthetic Derivatives of Lupane, Oleanane, Ursane and Dammarane Triterpenoids. AB - A variety of new and earlier synthesized lupane, oleanane, ursane and dammarane triterpenoids have been investigated for their inhibitory activity against alpha glucosidase. 2,3-Indole-21 beta-acetyl-20beta,28-epoxy-18alpha,19betaH-ursane and 3-oxo-3A-homo-3a-aza-20(S)-hydroxydammar-24(25)-ene were synthesized for the first time. The compounds 3, 4, 8-11 and 14 demonstrated strong in vitro inhibitory activity towards alpha-glucosidase with IC50 values of 37.5-115.1 uM. 3-Deoxy-3a-homo-3a-aza-28-cinnamoyloxy-20(29)-lupene, with an IC50 of 6.67 uM was 60-fold more active than the market drug acarbose. PMID- 26996015 TI - Cycloartane-Type Saponins from Astragalus tmoleus var. tmoleus. AB - Five known cycloartane-type glycosides were isolated from the roots of A. tmoleus Boiss. var. tmoleus. The identification of these compounds was mainly achieved by 1D and 2D NMR spectroscopic techniques and FABMS. The results of our studies confirm that triterpene saponins with the cycloartane-type skeleton might be chemotaxonomically significant for the genus Astragalus. PMID- 26996016 TI - Profiling and Metabolism of Sterols in the Weaver Ant Genus Oecophylla. AB - Sterols are essential to insects because they are vital for many biochemical processes, nevertheless insects cannot synthesize sterols but have to acquire them through their diet. Studies of sterols in ants are sparse and here the sterols of the weaver ant genus Oecophylla are identified for the first time. The sterol profile and the dietary sterols provided to a laboratory Oecophylla longinoda colony were analyzed. Most sterols originated from the diet, except one, which was probably formed via dealkylation in the ants and two sterols of fungal origin, which likely originate from hitherto unidentified endosymbionts responsible for supplying these two compounds. The sterol profile of a wild Oecophylla smaragdina colony was also investigated. Remarkable qualitative similarities were established between the two species despite the differences in diet, species, and origin. This may reflect a common sterol need/aversion in the weaver ants. Additionally, each individual caste of both species displayed unique sterol profiles. PMID- 26996017 TI - Steroidal Glucosides from the Rhizomes of Tacca chantrieri and Their Inhibitory Activities of NO Production in BV2 Cells. AB - Two new steroidal glucosides, chantriolides D and E (1 and 2), along with four known compounds, chantriolide A (3), chantriolide B (4), chantriolide C (5), and (25S)-spirost-5-en-3-ol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-[alpha-L rhamnopyranosyl-(1-->3)]-beta-D-glucopyranoside (6) were isolated from the rhizomes of Tacca chantrieri. Their structures were determined by 1D and 2D NMR spectroscopic and HR-ESI-MS data, as well as by comparison with reported data. Compounds 1 and 2 were found to show strong inhibitory NO effect in BV2 cells, with IC50 values of 12.45 and 59.03 uM, respectively. PMID- 26996018 TI - Antimicrobial Metabolites from a Marine-Derived Actinomycete in Vietnam's East Sea. AB - Two new compounds, a quinoline alkaloid (1) and a 1,4-dioxane derivative (2), were isolated from culture broth of the marine-derived actinomycete Micromonospora sp. (strain G019) by bioassay-guided fractionation. This actinomycete strain was isolated from sediment, collected at Cat Ba Peninsula, Vietnam. The taxonomic identification was achieved by analysis of 16S rRNA gene sequences. On the basis of morphological and phylogenetic evidence, strain G019 was assigned to the genus Micromonospora. The structures of 1 and 2 were established by spectroscopic data analysis, including one- and two-dimensional NMR, and MS. Compound 1 was found to have antibacterial activity against Escherichia coli (MIC: 48 ug/mL), Salmonella enterica (MIC: 96 ug/mL) and Enterococcus faecalis (MIC: 128 ug/mL), while compound 2 showed inhibitory activity against Enterococcusfaecalis (MIC: 32 ug/mL) and Candida albicans (MIC: 64 ug/mL). PMID- 26996019 TI - Aspidosperma-type Alkaloids from Melodinus suaveolens. AB - Three new aspidosperma-type alkaloids, 3-oxo-11-hydroxytabersonine (2), 1 1 hydroxytabersonine N-oxide (3) and 11-methoxytabersonine N-oxide (4), along with three known ones were isolated from the twigs and leaves of Melodinus suaveolens. The structures of the new compounds were elucidated by using spectroscopic methods, and circular dichroism experiments. The known compounds were identified by comparing their spectroscopic data with those reported in the literature. PMID- 26996020 TI - Molecular Docking and Binding Mode Analysis of Plant Alkaloids as in vitro and in silico Inhibitors of Trypanothione Reductase from Trypanosoma cruzi. AB - Trypanothione reductase (TryR) is a key enzyme in the metabolism of Trypanosoma cruzi, the parasite responsible for Chagas disease. The available repertoire of TryR inhibitors relies heavily on synthetic substrates of limited structural diversity, and less on plant-derived natural products. In this study, a molecular docking procedure using a Lamarckian Genetic Algorithm was implemented to examine the protein-ligand binding interactions of strong in vitro inhibitors for which no X-ray data is available. In addition, a small, skeletally diverse, set of natural alkaloids was assessed computationally against T. cruzi TryR in search of new scaffolds for lead development. The preferential binding mode (low number of clusters, high cluster population), together with the deduced binding interactions were used to discriminate among the virtual inhibitors. This study confirms the prior in vitro data and proposes quebrachamine, cephalotaxine, cryptolepine, (22S,25S)-tomatidine, (22R,25S)-solanidine, and (22R,25R) solasodine as new alkaloid scaffold leads in the search for more potent and selective TryR inhibitors. PMID- 26996021 TI - Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways. AB - Cordycepin, a major compound separated from Cordyceps sinensis, is known as a potential novel candidate for cancer therapy. Breast cancer, the most typical cancer diagnosed among women, remains a global health problem. In this study, the anti-breast cancer property of cordycepin and its underlying mechanisms was investigated. The direct effects of cordycepin on breast cancer cells both in in vitro and in vivo experiments were evaluated. Cordycepin exerted cytotoxicity in MCF-7 and MDA-MB-231 cells confirmed by reduced cell viability, inhibition of cell proliferation, enhanced lactate dehydrogenase release and reactive oxygen species accumulation, induced mitochondrial dysfunction and nuclear apoptosis in human breast cancer cells. Cordycepin increased the activation of pro-apoptotic proteins, including caspase-8, caspase-9, caspase-3 and Bax, and suppressed the expression of the anti-apoptotic protein, B-cell lymphoma 2 (Bcl-2). The inhibition on MCF-7-xenografted tumor growth in nude mice further confirmed cordycepin's anti-breast cancer effect. These aforementioned results reveal that cordycepin induces apoptosis in human breast cancer cells via caspase-dependent pathways. The data shed light on the possibility of cordycepin being a safe agent for breast cancer treatment. PMID- 26996022 TI - Absolute Stereochemistry of the beta-Hydroxy Acid Unit in Hantupeptins and Trungapeptins. AB - The beta-hydroxy/amino acid unit is a common structural feature of many bioactive marine cyanobacterial depsipeptides. In this study, the absolute stereochemistry of the beta-hydroxy acid moieties in hantupeptins and trungapeptins were determined through their synthesis and HPLC analysis of the Mosher ester derivatives. Synthesis of two3-hydroxy-2-methyloctanoic acid (Hmoa) stereoisomers, (2S,3R)-Hmoa and (2S,3S)-Hmoa, were achieved using diastereoselective asymmetric method and the retention times of all four Hmoa isomers were established indirectly by RPLC-MS analysis of their Mosher ester derivative standards. Based on the retention times of the standards, the absolute configuration of the Hmoa unit in hantupeptin C (3) and trungapeptin C (6) was assigned as (2R,3S)- and (2S,3R)-Hmoa, respectively. The use of the Mosher's reagents, coupled with HPLC analysis, provided a viable alternative to the absolute stereochemical determination of beta-hydroxy acid units in depsipeptides. PMID- 26996023 TI - Electron Ionization Mass Spectrometry-based Metabolomics Studies of Sophoraflavescens can Identify the Geographical Origin of Root Samples. AB - An electron ionization mass spectrometry (EI-MS)-based metabolomic approach was applied to Sophora flavescens to identify the geographical origin of each sample. The score plot from principal component analysis using the EI-MS data showed that Japanese S. flavescens samples tended to cluster away from Chinese S. flavescens samples. Statistical techniques showed that ions arising from kurarinol and kushenol H, which we previously identified as marker molecules for Japanese S. flavescens, were characteristic of Japanese S. flavescens. Therefore, metabolomics based on EI-MS data is a valuable tool for confirming the geographical origins of S. flavescens samples. The results suggest that EI-MS based metabolomics is suitable for the quality control of traditional medicines containing many components. PMID- 26996024 TI - Qualitative and Quantitative Analysis of Flower Pigments in Chocolate Cosmos, Cosmos atrosanguineus, and its Hybrids. AB - Two major anthocyanins, cyanidin 3-O-glucoside and 3-O-rutinoside, were isolated from the black flowers of Cosmos atrosanguineus cultivar 'Choco Mocha', together with three minor anthocyanins, cyanidin 3-O-malonylglucoside, pelargonidin 3-O glucoside and 3-O-rutinoside. A chalcone, butein 4'-O-glucoside and three minor flavanones were isolated from the red flowers of C. atrosanguineis x C. sulphureus cultivar 'Rouge Rouge'. The anthocyanins and chalcone accumulation of cultivar 'Choco Mocha' and its hybrid cultivars 'Brown Rouge', 'Forte Rouge', 'Rouge Rouge' and 'Noel Rouge' was surveyed by quantitative HPLC. Total anthocyanins of black flower cultivars 'Choco Mocha' and 'Brown Rouge' were 3-4 folds higher than that of the red flower cultivar 'Noel Rouge'. On the other hand, total chalcone of 'Noel Rouge' was 10-77-folds higher compared with those of other cultivars, 'Brown Rouge', 'Forte Rouge' and 'Rouge Rouge'. It was shown that the flower color variations from red to black of Chocolate Cosmos and its hybrids are due to the difference in the relative amounts of anthocyanins and chalcone. PMID- 26996025 TI - A New Geranylated Chalcone from Andrographis lobelioides. AB - A new O-geranylated chalcone, 2'-hydroxy-2-methoxy-4'-O-[(E)-3,7-dimethyl-2,6 octadienyl] chalcone (1), together with three known flavones, 5-hydroxy-7,2' dimethoxyflavone (2), skullcapflavone I (3) and echioidin (4), were isolated from the leaves of Andrographis lobelioides. The structure of 1 and the known compounds (2-4) were achieved by extensive 1D and 2D NMR spectral and chemical studies. PMID- 26996026 TI - Pterocarpans from Derris laxiflora. AB - Six compounds were isolated from Derris laxiflora Benth., including two new pterocarpans, 7,6'-dihydroxy-3'-methoxypterocarpan (1) and derrispisatin (2), as well as four known ones, lespedezol D, (3), secundiflorol 1 (4), 6a hydroxymaackiain (5) and pisatin (6). The structures of these compounds were determined by analysis of their spectroscopic data. PMID- 26996027 TI - Acetophenones Isolated from Acronychia pedunculata and their Anti-proliferative Activities. AB - Study of the chemical constituents of Acronychia pedunculata (L.) Miq. (Rutaceae) stems collected in Taiwan led to the isolation and identification of eight known and three new acetophenones, named acrophenone A (1), B (2), and C (3). Of them, acrovestone (5), acropyrone (6) and acrovestenol (7), which are dimer compounds, strikingly inhibited the proliferation of human leukemia cell lines. PMID- 26996028 TI - Xanthones from Garcinia propinqua Roots. AB - Phytochemical investigation of Garcinia propinqua roots led to the isolation and identification of a new xanthone, doitunggarcinone D (1), together with 15 known compounds (2-16). Their structures were elucidated by intensive analysis of spectroscopic data. Compounds 3, 6, 7, 14, 15 and 16 exhibited strong antibacterial activity against Bacillus subtilis TISTR 088 with MIC values in the range of 1-4 ug/mL. Compounds 3, 7, 10 and 14 also showed good antibacterial activity against B. cereus TISTR 688 with MIC values ranging from 4-8 ug/mL. PMID- 26996029 TI - A New Antibacterial Tetrahydronaphthalene Lignanamide, Foveolatamide, from the Stems of Ficusfoveolata. AB - An antibacterial assay-guided isolation of the crude ethyl acetate extract from Ficus foveolata stems afforded four compounds, including a tetrahydronaphthalene lignanamide, foveolatamide (1), together with two known lignanamides, flavifloramide B (2) and N-trans-grossamide (3), and a known phenolic amide, N trans-feruloyltyramine (4). The structures of these compounds were established on the basis of NMR spectroscopic and MS techniques. Among the isolated compounds, only 1 showed satisfactory antibacterial activities against Streptococcus pyogenes, with an MIC and MBC value of 45 uM. This is the first report of these four compounds from the stems of F. foveolata. PMID- 26996031 TI - Polyphenols and Volatile Compounds in Commercial Chokeberry (Aronia melanocarpa) Products. AB - Aronia melanocarpa (Michx.) Elliott commercial products (dried fruit, juice and compote) were analyzed for their polyphenol content by chromatographic and spectrophotometric analyses in order to ascertain the fate of this group of compounds when fresh fruit is processed and sold in different forms on the market. Different classes of polyphenols were investigated: hydroxycinnamic derivatives ranged from 0.65 mg/g to 4.30 mg/g, flavonoids from 0.36 mg/g to 1.12 mg/g, and anthocyanins from 0.65 to 7.08 mg/g sample. 4-O-Caffeoyl-quinic acid was tentatively identified for the first time in Aronia. In order to characterize better chokeberry juice, a GC profile of aroma compounds was obtained. The aroma juice compounds belong mainly to the chemical classes of alcohols (48.9%) and ketones (30.28%). The most abundant compound is 3-penthen-2-one (23.6%). PMID- 26996032 TI - Volatile Components of the Stressed Liverwort Conocephalum conicum. AB - The Type-II Japanese Conocephalum conicum, which is known to have (+)-bornyl acetate as a marker compound, was put in the stressed condition to start biosynthesis of a phenyl propanoid, trans-methyl cinnamate. Analysis of the HS SPME GC/MS of stressed C. conicum showed trans-methyl cinnamate as a major component. This phenomenon results in some confusion from the chemotype perspective since trans-methyl cinnamate is only present in type-III Japanese C. conicum. PMID- 26996030 TI - Antifungal and Cytotoxic Assessment of Lapachol Derivatives Produced by Fungal Biotransformation. AB - In the screening for biological active compounds, the biotransformation processes catalyzed by filamentous fungi are useful because they can provide information about the possible appearance of toxic metabolites after oral administration and also generate new leads. In this paper, biotransformation of lapachol (1) by three fungal strains, Mucor circinelloides NRRL3631, Botrytis cinerea UCA992 and Botrytis cinerea 2100, has been investigated for the first time. Lapachol (1) was biotransformed into avicequinone-A (2) by M circinelloides, 3'-hydroxylapachol (3) by B. cinerea, and into dehydro-alpha-lapachone (4) by both fungi. All these compounds were evaluated for their cytotoxic activities. The metabolite 2 displayed non-selective cytotoxicity against tumor and normal cell lines, 3 did not show cytotoxicity against the same cells, while 4 showed higher cytotoxicity against cancer cell lines than lapachol (1). The transformation of 1 into harmless and reactive metabolites evidences the importance of the evaluation of drug metabolism in the drug discovery process. Antifungal potential of lapachol (1) and its metabolites 2 and 4 against B. cinerea has also been evaluated. Dehydro-alpha-lapachone (4) has been shown to be less toxic to fungal growth than lapachol (1), which indicates a detoxification mechanism of the phytopathogen. PMID- 26996033 TI - Chemical Composition of the Essential Oil of Bupleurum fontanesii (Apiaceae) Growing Wild in Sicily and its Activity on Microorganisms Affecting Historical Art Crafts. AB - Hydrodistillation of the flowers (BpFI) of and fruits (BpFr) of Bupleurumfontanesii Guss. ex Caruel gave two oils that were analyzed by GC and GC MS. The main components were alpha-elemol (16.7%), caryophyllene oxide (16.4%) and heptacosane (15.9%) in BpFl, and spathulenol (16.8%), caryophylladienol I (13.2%) and alpha-elemol (12.8%) in BpFr. A good antimicrobial activity against several microorganisms, including Bacillus subtilis, Staphylococcus aureus, Fusarium oxysporum and Aspergillus niger, all infesting historical art craft, was also determined. PMID- 26996034 TI - Chemical Composition and Antimicrobial Activity of the Essential Oil from Aerial Parts of Algerian Pulicaria mauritanica. AB - One oil sample isolated from aerial parts of Pulicaria mauritanica Coss. from Western Algeria has been analyzed by GC(RI), GC-MS and 13C NMR. In total, 21 components, accounting for 97.0% of the oil, were identified. Then, 36 oil samples coming from plants harvested at two flowering periods in three locations were analyzed by GC(RI) and 13C NMR. Although all the oil samples exhibited similar composition, dominated by carvotanacetone (89.2-96.1%), the yield of essential oil varied drastically from sample to sample (0.35-1.44%), depending on the location of harvest. The essential oil displayed moderate antimicrobial effect against bacteria, yeast and filamentous fungi (MIC = 2-4 uL/mL). PMID- 26996036 TI - In vivo Cytotoxicity Studies of Amaryllidaceae Alkaloids. AB - The plant family Amaryllidaceae is recognizable for its esthetic floral characteristics, its widespread usage in traditional medicine as well as its unique alkaloid principles. Few alkaloid-producing families rival the Amaryllidaceae in terms of the diversity of its structures as well as their wide applicability on the biological landscape. In particular, cytotoxic effects have come to be a dominant theme in the biological properties of Amaryllidacea alkaloids. To this extent, a significant number of structures have been subjected to in vitro studies in numerous cell lines from which several targets have been identified as promising chemotherapeutics. By contrast, in vivo models of study involving these alkaloids have been carried out to a lesser extent and should prove crucial in the continued development of a clinical target such as pancratistatin. This survey examines the cytotoxic effects of Amaryllidaceae alkaloids in vivo and contrasts these against the corresponding in vitro effects. PMID- 26996035 TI - Origanum vulgare and Thymbra capitata Essential Oils from Spain: Determination of Aromatic Profile and Bioactivities. AB - Oregano (Thymbra capitata and Origanum vulgare) essential oils (EOs), cultivated and extracted in the South-East of Spain, were analysed by GC/MS to determine their composition. (E)-beta-Caryophyllene (0.5-4.9%), thymol (0.2-5.8%), p-cymene (3.8-8.2%), gamma-terpinene (2.1-10.7%) and carvacrol (58.7-77.4%) were determined as the main molecules. This characterisation was completed with enantioselective gas chromatography, where (-)-(E)-beta-caryophyllene, (+)-a- pinene and (+)-beta-pinene were determined as the main enantiomers. Antioxidant activity was evaluated positively by several methods, accounting for activity against free radicals and reducing power. Important inhibitory activity on lipoxygenase (LOX) and acetylcholinesterase (AChE) was observed supporting potential anti-inflammatory, anti-Alzheimer and insecticidal activities, mainly due to carvacrol. These properties support the potential use of oregano EOs as natural cosmetic and natural pharmaceutical ingredients. PMID- 26996037 TI - [Not Available]. PMID- 26996038 TI - [REASONS FOR NON-VACCINATION AGAINST INFLUENZA IN HEALTH WORKERS]. AB - INTRODUCTION: Health workers are a risk group for acquisition and transmission of influenza. Therefore each year the vaccine is indicated for them. However vaccination coverage against seaso nable influenza virus in our country is often low. OBJECTVES: To determine why the professionals of health centers have low rates of vaccination against influenza. knowing the reasons for to have intention to be vaccinated and analyze knowledge about influenza and vaccination. MATERIAL AND METHODS: A descriptive study carried out in Hospital Center of Vigo between 2014-2015. Data were collected by a self-administered questionnaire aimed at health professionals. Variables recorded were age, sex, profession, workplace, work experience, previous influenza vaccines, intention to be vaccinated, reasons for non-vaccination and knowledge about the disease and influenza vaccine. Statistical analysis was performed with the PSPP program and the associations between variables were evaluated using Chi-square test. RESULTS: 375 questionnaires were obtained. Only 18 % of workers were vaccinated last season. The reasons for not having intention to be vaccinated were: believe that it is not necessary (28 %), it is not effective (27 %) and risk of side effects (26 %). The main reason to have intention to be vaccinated was self-protection in 71 %. Working in a health center means risk of getting the flu for 66 % of survey respondents, though 68 % of them think unimportant the vaccination in health professionals. Statistical significance between sexand vaccination lastseason was found (p = 0.023). CONCLUSIONS: It is necessary to increase knowledge about influenza and vaccination by developing specific training to improve vaccination coverage among health care workers. PMID- 26996039 TI - [Psychometric properties of an instrument to evaluate the nurse attitude towards good practice guides]. AB - The Guides of Good Practices (GGP) are necessary tools in the universal healthcare and in the clinical management, providing the user/patient with a major quality in the assistance, in order to optimize and reinforce an individualized attention into action, taking into account the best scientific evidence. The literature provides different references to the development of the GGP, but there is little knowledge about the attitude of professionals towards them, since most of the studies that exist are qualitative. Therefore, the aim of this work is to construct and validate a Likert scale which could assess the attitude of the nurse towards GGP. The methodology used was quantitative, descriptive, cross, opinion, anonymous and also it could validate a scale via the following measurements: content validation by experts, correlation between items, external reliability, internal consistency, stability and exploratory factor analysis. The result was a scale consisting of 20 items that refer to the attitude toward the GGP, with a percentage of agreement among experts over 75 % on all the items, and a significant Pearson correlation between the pre-test and post-test in all variables, but for three. The internal consistency measured by Cronbach's alpha was 0.878. These results are acceptable in terms of the psychometric characteristics of the instrument, with easy and fast administration and simple in their interpretation, allowing quantifying and generating knowledge about the attitudes of nurses towards GGP. PMID- 26996040 TI - [INMERSION IN HOT WATER: A NATURAL HELPER IN LABOUR]. AB - INTRODUCTION: The pain during the birth process is the result of a pile of physiological, psychological and socio-cultural stimulus. In our society, epidural analgesia is the most common technique used in obstetrics to relieve this pain, despite not being harmless. However, there are other complementary techniques based on methods that have demonstrated analgesic effects and they benefit of lacking adverse effects either on the mother or on the fetus. Among these methods is the immersion in warm water (WI). The aim of this review is to show the usefulness, advantages and disadvantages of WI, to make it an accessible resource for pregnant women and those who are responsible for their care. METHODS: Literature review about Water Immersion during the first and second stage of labor. RESULTS: The WI as a method to relieve discomfort and pain during labor was popularized by the obstetrician Michel Odent in 7980s. The Spanish Society of Gynecology and Obstetrics, among other associations, highly recommend its use during the cervical dilation period. It is benificial for the mother blood circulation, psychologically and for body mechanics; however, this use in the second stage of labor seems to be more controversial. CONCLUSIONS: WI is an analgesic non-invasive, accessible and affordable. Its use is associated with lower rates of intervention by professionals and provide a more focused attention on the needs of pregnant women. PMID- 26996041 TI - [GUIDE TO DEVELOPING A RESEARCH PROJECT. PART ONE]. AB - This work aims to develop a practical guide to writing a research project. PMID- 26996042 TI - [NURSING CARE PROTOCOL ON MANAGEMENT OF RADIODERMITIS]. AB - INTRODUCTION: Cases of radiation recall may be experienced by radiotherapy patients, which are named as radiodermitis. To gradate it the RTOG (Radiation Therapy Oncology Group) scale is the most used. Due to the complexity on the management of radiotherapy, a protocol based on the evidence is stablished to prevent and treat it. MATERIAL AND METHODS: Bibliographic revision of main data bases from last six years. RESULTS: 14 different studies which have the criteria for their inclusion are selected. These studies will gather, with different levels of evidence, several prevention and treatment methods and products for radiodermitis. DISCUSSION: To prevent it from happening, it is a must to clean and dry the skin appropriately. Urea, hyaluronic acid and Tex-OE based creams have shown their effectiveness on grades 0-1. Regarding treatment, the use of medium-high corticoids, the barrier creams, silver sulfadiazine, hyaluronic acid and no sting barrier film can reduce the gravity of the wounds. The use of the healing in humid environments is also recommended on the treatment of radiodermitis. Some products like hydrocolloids, silver dressings and hydrogel also improve the scarring. CONCLUSION: Managing radiodermitis is a complex matter. Therefore the action protocol based on evidence is the ideal tool to improve the efficiency and effectiveness of the cares, giving an increase on the tolerance to treatment and a reduction on the public health cost and a higher quality of life fo rpatients. PMID- 26996043 TI - [EVALUATION OF THE EFFECTIVENESS OF AN OIL EXTRACT OF ROSEHIP IN THE PREVENTION OF EPITHELITIS DUE TO RADIOTHERAPY IN PATIENTS WITH HEAD AND NECK CANCER]. AB - INTRODUCTION: Epithelitis is a frequent side effect in radiotherapy treatments (RT). OBJECTIVE: To evaluate the effectiveness of Rosehip Oil (ARM, Repavar(r)) in the prevention of epithelitis in patients with head and neck cancer (HNC) treated with intensity modulated radiotherapy (IMRT). MATERIAL AND METHODS: An interventionist, prospective, exploratory, controlled and open clinical study. Between May and October 2013, 28 patients were included in the study. After signing the informed consent form, the patients were provided with ARM to apply this twice daily from the beginning of the treatment. All of them had a prescribed dose of IMRT >= 60 Gy. They were evaluated weekly by nurses on the ward. A photographic monitoring of the skin with a registered grade of epithelitis and with signs of pain or other was carried out. The control group was formed of 34 consecutive patients with HNC treated with IMRT months prior to the study, whose skin treatment had been different products. RESULTS: Both groups were comparable (age, sex, region and RT dose). In the study group (ARM), the number of treatments per patient (p = 0.3) and the natural days for treatment per patient (p = 0.38) were less; also, the number of patients who required treatments and who suffered from radiodermitis of III-IV grade, were less. It is probable that the limited specimen size may have influenced in the statistics. CONCLUSIONS: The effectiveness of ARM in the prevention of severe epithelitis in patients with HNC treated with RT is, at least, as effective (or more effective) as other and more common skin treatments. A randomized study would be required to confirm these findinas. PMID- 26996044 TI - [COMPREHENSIVE GERIATRIC ASSESSMENT SCALES]. AB - The process of comprehensive geriatric assessment is one of the key elements of geriatric care management aimed at the population. it includes evaluating the clinical, functional, mental and social aspects of aging result and/or pathological processes that appear at this stage of the life cycle. For their achievement, as well as other tools, professionals have a large number of validated rating scales specifically designed in the assessment of the different areas or fields. Its use can be very useful, especially for the objectification of evaluation results. The future of research in this area goes through deepening the adequacy of the scales to the characteristics and needs of older people in each care level or place of care. PMID- 26996048 TI - Parinaud's oculoglandular syndrome: A case report. AB - CLINICAL CASE: A 33-year old woman presents with unilateral granulomatous conjunctivitis, ipsilateral regional lymphadenopathy and fever. A Bartonella henselae infection is demonstrated by indirect immunofluorescence, and a diagnosis of a Parinaud's oculoglandular syndrome is established. Outcome after treatment with oral doxycycline is satisfactory. DISCUSSION: Parinaud's oculoglandular syndrome is the most frequent ocular manifestation of a Bartonella henselae infection. PMID- 26996049 TI - Iris alterations after DSAEK. AB - OBJECTIVE: To evaluate a series of case that developed iris changes after performing Descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS: Retrospective study of eyes that developed iris abnormalities, such as pupil ovalisation, iris atrophy, iridocorneal synechiae, mydriatic pupil, and pigmentary changes after performing DSAEK in a tertiary hospital. RESULTS: In a series of the first 32 DSAEK procedures performed, new single or mixed iris alterations were observed in 12 eyes (37.5%). Iris-corneal synechiae were observed in 7 eyes, corectopias in 9 eyes, iris atrophy in 3 cases, and one case developed an areflexic mydriatic pupil. Long-term pigment dispersion at the edge of the lenticule was observed in 12 eyes. The alterations occurred after three months from the surgery. In the evaluation of the associated factors, malignant glaucoma had occurred in 1 case, 2 eyes had required a second surgery, one case by re-DSAEK, and the other one by removing the intraocular lens due to lens opacification. Two cases had a shallow anterior chamber. No relationship was found between the thickness of the peripheral lenticule and the presence of synechiae. CONCLUSION: Iris changes regarding DSAEK are possible. A discussion is presented on the relationship between increased intraocular pressure due to air in anterior chamber and its relationship with ischaemia and secondary alterations in the iris. PMID- 26996050 TI - The impact of sharing: The use of shared medical appointments to allow providers to increase treatment access for substance use and related disorders. PMID- 26996051 TI - I see how you feel: Recipients obtain additional information from speakers' gestures about pain. AB - OBJECTIVE: Despite the need for effective pain communication, pain is difficult to verbalise. Co-speech gestures frequently add information about pain that is not contained in the accompanying speech. We explored whether recipients can obtain additional information from gestures about the pain that is being described. METHODS: Participants (n=135) viewed clips of pain descriptions under one of four conditions: 1) Speech Only; 2) Speech and Gesture; 3) Speech, Gesture and Face; and 4) Speech, Gesture and Face plus Instruction (short presentation explaining the pain information that gestures can depict). Participants provided free-text descriptions of the pain that had been described. Responses were scored for the amount of information obtained from the original clips. FINDINGS: Participants in the Instruction condition obtained the most information, while those in the Speech Only condition obtained the least (all comparisons p<0.001). CONCLUSIONS: Gestures produced during pain descriptions provide additional information about pain that recipients are able to pick up without detriment to their uptake of spoken information. PRACTICE IMPLICATIONS: Healthcare professionals may benefit from instruction in gestures to enhance uptake of information about patients' pain experiences. PMID- 26996053 TI - The nature of evidence. PMID- 26996052 TI - Increasing referral rate for screening colonoscopy through patient education and activation at a primary care clinic in New York City. AB - OBJECTIVE: Colorectal cancer could be prevented through regular screening. Individuals age 50 and older are recommended to get screened via colonoscopy. Because physician referral is a major predictor of colonoscopy completion, two low-cost, evidence-based interventions were tested to increase referrals by activating patients to self-advocate. METHODS: This study compared the impact of a pre-visit educational handout that prompts patients to discuss colonoscopy with their physician with the handout plus brief counseling through exit interviews and chart reviews. The main outcome was physician referral. RESULTS: Medical charts were reviewed for eligibility: 130 control patients (Arm 1), 45 patients who received the educational handout and health counseling (Arm 2), and 50 patients who received only the handout (Arm 3). Colonoscopy referral rates increased from 24.6% in Arm 1 to 44.4% and 52.0% in Arms 2 and 3, respectively (p=0.001). The proportion of exit interview participants who discussed colonoscopy with their doctor increased from 68.8% in Arm 1 to 76.5% and 88.9% in Arms 2 and 3, respectively. CONCLUSIONS: Results indicate that both interventions are effective at increasing colonoscopy referrals. PRACTICAL IMPLICATIONS: Results suggest that an educational handout alone is sufficient in prompting patient-initiated discussions about colonoscopy. PMID- 26996054 TI - Measuring spinal surgical success: the proportion achieving acceptable symptoms: Keep it simple but not simplistic. AB - Commentary On: Fekete TF, Haschtmann D, Kleinstuck FS, Porchet F, Jeszenszky D, Mannion AF. What level of pain are patients happy to live with after surgery for lumbar degenerative disorders? Spine J 2016:16:S12-18 (in this issue). PMID- 26996055 TI - A non-systematic review of publications that have influenced my practice. PMID- 26996056 TI - Surgeons who have influenced my surgical career. PMID- 26996057 TI - Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging. AB - We demonstrate a simple dual-mode multiplexed array-in-well immunoassay for simultaneous classification and detection of serum IgG and IgM antibodies against influenza A and human adenoviruses based on the color and position of the upconversion luminescence on the array. Biotinylated influenza A/H1N1 and A/H5N1 as well as adenovirus serotype 2 and 5 hexon antigens along with positive and negative controls were printed in an array format onto the bottom of streptavidin coated microtiter wells. The anti-influenza A and antiadenovirus antibodies present in the sample were captured to the array and detected with antihuman antibody-coated upconverting nanophosphors (UCNPs). The green emitting UCNPs (NaYF4:Yb(3+),Er(3+)) coated with antihuman IgG and blue emitting UCNPs (NaYF4:Yb(3+),Tm(3+)) coated with antihuman IgM were used to detect human IgG and IgM antibodies, respectively. The emission of the bound UCNPs was imaged free of autofluorescence with anti-Stokes photoluminescence microwell imager. No spectral cross-talk was observed between green and blue emitting UCNPs. Also the cross reactivities between UCNP-conjugates and immobilized human IgG and IgM antibodies were negligible. Position of the signal on the array defined the antigen specificity and the antibody class was defined by the color of the upconversion luminescence. This technology could be used for differentiation between acute infection from past infection and immunity. Additionally, the class of the antibody response can be used for the differentiation between primary and secondary infections, hence, facilitating epidemiological seroprevalence studies. PMID- 26996058 TI - Dietary fat intakes in Irish adults in 2011: how much has changed in 10 years? AB - Imbalances in dietary fat intakes are linked to several chronic diseases. This study describes dietary intakes and food sources of fat and fatty acids in 1051 Irish adults (aged 18-90 years), using data from the 2011 national food consumption survey, the National Adult Nutrition Survey. It also compares current intakes for 18-64-year-olds with those reported in the last such survey in 2001, the North/South Ireland Food Consumption Survey. Dietary fat intakes were estimated using data from 4-d semi-weighed (2011) and 7-d estimated (2001) food diaries. In 2011, intakes for 18-64-year-olds were as follows: total fat, 34.1 (sd 6.1) % total energy (%TE); SFA, 13.3 (sd 3.3) %TE; MUFA, 12.5 (sd 2.6) %TE; PUFA, 6.1 (sd 2.2) %TE; and trans-fat, 0.511 (sd 0.282) %TE. Apart from MUFA, intakes decreased (P65 years had the highest intakes of SFA; however, intakes were typically higher than UK-recommended values for all groups. In contrast, intakes of long-chain n-3 fatty acids were lowest in younger age groups. Intakes of trans-fat were well within UK-recommended levels. Although there have been some improvements in the profile of intakes since 2001, imbalances persist in the quantity and quality of dietary fat consumed by Irish adults, most notably for total and SFA and for younger age groups for long-chain n-3 fatty acids. PMID- 26996059 TI - Success of Targeted Strategies to Reduce Methicillin-Susceptible Staphylococcus aureus Infections in the Neonatal Intensive Care Unit. PMID- 26996060 TI - Lack of Comprehensive Outbreak Detection in Hospitals. AB - Timely identification of outbreaks of hospital-associated infections is needed to implement control measures and minimize impact. Survey results from 33 hospitals indicated that most hospitals lacked a formal cluster definition and all targeted a very limited group of prespecified pathogens. Standardized, statistically based outbreak detection could greatly improve current practice. PMID- 26996061 TI - Influenza Vaccination Requirements for Healthcare Personnel in U.S. Hospitals: Results of a National Survey. PMID- 26996062 TI - Heat-Induced Soluble Protein Aggregates from Mixed Pea Globulins and beta Lactoglobulin. AB - The present work investigates the formation of protein aggregates (85 degrees C, 60 min incubation) upon heat treatment of beta-lactoglobulin (betalg)-pea globulins (Glob) mixtures at pH 7.2 and 5 mM NaCl from laboratory-prepared protein isolates. Various betalg/Glob weight ratios were applied, for a total protein concentration of 2 wt % in admixture. Different analytical methods were used to determine the aggregation behavior of "mixed" aggregates, that is, surface hydrophobicity and also sulfhydryl content, protein interactions by means of SDS-PAGE electrophoresis, and molecule size distribution by DLS and gel filtration. The production of "mixed" thermal aggregates would involve both the formation of new disulfide bonds and noncovalent interactions between the denatured betalg and Glob subunits. The majority of "mixed" soluble aggregates displayed higher molecular weight and smaller diameter than those for Glob heated in isolation. The development of pea-whey protein "mixed" aggregates may help to design new ingredients for the control of innovative food textures. PMID- 26996063 TI - Mitochondrial cytopathies. AB - Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Most of mitochondrial proteins are encoded by the nuclear DNA (nDNA) whereas a very small fraction is encoded by the mitochondrial DNA (mtDNA). Mutations in mtDNA or mitochondria-related nDNA genes can result in mitochondrial dysfunction which leads to a wide range of cellular perturbations including aberrant calcium homeostasis, excessive reactive oxygen species production, dysregulated apoptosis, and insufficient energy generation to meet the needs of various organs, particularly those with high energy demand. Impaired mitochondrial function in various tissues and organs results in the multi-organ manifestations of mitochondrial diseases including epilepsy, intellectual disability, skeletal and cardiac myopathies, hepatopathies, endocrinopathies, and nephropathies. Defects in nDNA genes can be inherited in an autosomal or X-linked manners, whereas, mtDNA is maternally inherited. Mitochondrial diseases can result from mutations of nDNA genes encoding subunits of the electron transport chain complexes or their assembly factors, proteins associated with the mitochondrial import or networking, mitochondrial translation factors, or proteins involved in mtDNA maintenance. MtDNA defects can be either point mutations or rearrangements. The diagnosis of mitochondrial disorders can be challenging in many cases and is based on clinical recognition, biochemical screening, histopathological studies, functional studies, and molecular genetic testing. Currently, there are no satisfactory therapies available for mitochondrial disorders that significantly alter the course of the disease. Therapeutic options include symptomatic treatment, cofactor supplementation, and exercise. PMID- 26996064 TI - Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals. AB - Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination. PMID- 26996065 TI - Preventive effect of chrysin on experimental autoimmune uveitis triggered by injection of human IRBP peptide 1-20 in mice. AB - Uveitis is a common cause of blindness worldwide. Experimental autoimmune uveitis (EAU) is an animal model of noninfectious uveitis. Chrysin (5,7-dihydroxyflavone) is a member of the flavonoid family and has anti-inflammatory effects. We immunized C57BL/6J mice with human interphotoreceptor retinoid-binding protein peptide 1-20 to induce EAU. Chrysin was administered intragastrically at 25 mg/kg daily to the chrysin-treated mice from 3 days before immunization to 21 days after immunization. Vehicle was administered to the mice in the control group according to the same protocol. Lower clinical and histopathological scores, increased integrity of the blood-retinal barrier (BRB) and higher expression of tight junction proteins were observed in the chrysin-treated mice. Chrysin significantly decreased the proportions of Th1, Th17 and CD4+CD3+CD62L+ Th0 cells, and increased the proportion of Treg cells. Both macrophage infiltration and the expression of inducible nitric oxide synthase in the retina were efficiently inhibited by chrysin treatment. In chrysin-treated mice, the expression of interferon-gamma, interleukin (IL)-17A, IL-6, IL-1beta and tumor necrosis factor-alpha was reduced in the retina, whereas higher levels of transforming growth factor-beta were detected. Furthermore, NF-kappaBp65 was downregulated after chrysin treatment. In conclusion, as an anti-inflammatory molecule, chrysin exerts a preventive effect on EAU by modulating the balance among helper T-cell subsets and suppressing ocular inflammation, thereby maintaining the integrity of the BRB. PMID- 26996066 TI - MCP-1-induced ERK/GSK-3beta/Snail signaling facilitates the epithelial mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells. AB - Monocyte chemoattractant protein-1 (MCP-1) is a chemotactic cytokine that can bind to its receptor cysteine-cysteine chemokine receptor 2 (CCR2) and plays an important role in breast cancer cell metastasis. However, the molecular mechanisms underlying MCP-1-induced alterations in cellular functions during tumor progression are poorly understood. Here, we showed that MCP-1 stimulated the epithelial-mesenchymal transition (EMT) and induced the tumorigenesis of breast cancer cells by downregulating E-cadherin, upregulating vimentin and fibronectin, activating matrix metallopeptidase-2 (MMP-2), and promoting migration and invasion. Moreover, MCP-1 treatment reduced glycogen synthase kinase-3beta (GSK-3beta) activity via the MEK/ERK-mediated phosphorylation of serine-9 in MCF-7 cells. The inhibition of MEK/ERK by U0126 attenuated the MCP-1 induced phosphorylation of GSK-3beta and decreased the expression of Snail, an EMT-related transcription factor, leading to the inhibition of MCF-7 cell migration and invasion. Inactivation of GSK-3beta by LiCl (lithium chloride) treatment notably increased MMP-2 activity, vascular endothelial growth factor expression and EMT of MCF-7 cells. These findings revealed that MCP-1-induced EMT and migration are mediated by the ERK/GSK-3beta/Snail pathway, and identified a potential novel target for therapeutic intervention in breast cancer. PMID- 26996067 TI - Impaired T-cell differentiation in diabetic foot ulceration. AB - Foot ulceration is one of the most debilitating complications associated with diabetes, but its cause remains poorly understood. Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing. However, few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes. In this study, we analysed the T-cell receptor (TCR) repertoire diversity in TCR alphabeta+ T cells. We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers. Our results showed that diabetic individuals, especially those with foot ulcers, have a significantly lower naive T-cell number and a poorer TCR-Vbeta repertoire diversity. We also showed that the reduced TCR Vbeta repertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells, the major source of tumour necrosis factor alpha production, which was even more pronounced in patients with acute foot ulceration. Moreover, the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients. In conclusion, effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers. This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care. PMID- 26996068 TI - miR-146a negatively regulates NK cell functions via STAT1 signaling. AB - It is known that natural killer (NK) cell function is downregulated in chronic hepatitis B (CHB)-infected patients and in hepatic carcinoma (HCC) patients, but the mechanisms underlying this functional downregulation are largely unclear. In this study, microRNA (miR)-146a expression increased in NK cells from CHB and HCC patients compared with NK cells from healthy donors, and miR-146a levels were negatively correlated to NK cell functions. Overexpression of miR-146a reduced NK cell-mediated cytotoxicity and the production of interferon (IFN)-gamma and tumor necrosis factor-alpha, which were reversed upon inhibition of miR-146a. In NK cells, miR-146a expression was induced by interleukin (IL)-10 and transforming growth factor-beta, but reduced after treatment with interleukin-12, IFN-alpha and IFN-beta. We further revealed that miR-146a regulated NK cell functions by targeting STAT1. Taken together, upregulated miR-146a expression, at least partially, attributes to NK cell dysfunction in CHB and HCC patients. Therefore, miR-146a may become a therapeutic target with great potential to ameliorate NK cell functions in liver disease. PMID- 26996070 TI - Arthritis-induced alveolar bone loss is associated with changes in the composition of oral microbiota. AB - Rheumatoid arthritis (RA) and periodontitis (PD) are chronic inflammatory disorders that cause bone loss. PD tends to be more prevalent and severe in RA patients. Previous experimental studies demonstrated that RA triggers alveolar bone loss similarly to PD. The aim of this study was to investigate if arthritis induced alveolar bone loss is associated with modification in the oral microbiota. Checkerboard DNA-DNA hybridization was employed to analyze forty oral bacterial species in 3 groups of C57BL/6 mice: control (n = 12; without any challenge); Y4 (n = 8; received oral inoculation of Aggregatibacter Actinomycetemcomitans strain FDC Y4) and AIA group (n = 12; chronic antigen induced arthritis). The results showed that AIA and Y4 group exhibited similar patterns of bone loss. The AIA group exhibited higher counts of most bacterial species analyzed with predominance of Gram-negative species similarly to infection-induced PD. Prevotella nigrescens and Treponema denticola were detected only in the Y4 group whereas Campylobacter showae, Streptococcus mitis and Streptococcus oralis were only found in the AIA group. Counts of Parvimonas micra, Selenomonas Noxia and Veillonella parvula were greater in the AIA group whereas Actinomyces viscosus and Neisseira mucosa were in large proportion in Y4 group. In conclusion, AIA is associated with changes in the composition of the oral microbiota, which might account for the alveolar bone loss observed in AIA mice. PMID- 26996071 TI - Excess VO2 during ramp exercise is positively correlated to intercostal muscles deoxyhemoglobin levels above the gas exchange threshold in young trained cyclists. AB - We assessed respiratory muscles oxygenation responses during a ramp exercise to exhaustion and further explored their relationship with the non-linear increase of VO2 (VO2 excess) observed above the gas-exchange threshold. Ten male cyclists completed a ramp exercise to exhaustion on an electromagnetically braked cycle ergometer with a rate of increment of 30Wmin(-1) with continuous monitoring of expired gases (breath-by-breath) and oxygenation status of intercostal muscles. Maximal inspiratory and expiratory pressure measurements were taken at rest and at exhaustion. The VO2 excess represents the difference between VO2max observed and VO2max expected using linear equation between the VO2 and the intensity before gas-exchange threshold. The deoxyhemoglobin remained unchanged until 60% of maximal aerobic power (MAP) and thereafter increased significantly by 37+/-18% and 40+/-22% at 80% and 100% of MAP, respectively. Additionally, the amplitude of deoxyhemoglobin increase between 60 and 100% of MAP positively correlated with the VO2 excess (r=0.69, p<0.05). Compared to exercise start, the oxygen tissue saturation index decreased from 80% of MAP (-4.8+/-3.2%, p<0.05) onwards. At exhaustion, maximal inspiratory and expiratory pressures declined by 7.8+/-16% and 12.6+/-10% (both p<0.05), respectively. In summary, our results suggest a significant contribution of respiratory muscles to the VO2 excess phenomenon. PMID- 26996072 TI - Numerical study on the effect of uncinectomy on airflow modification and ventilation characteristics of the maxillary sinus. AB - In this study, we examined the effect of uncinectomy on the alteration in local airflows and on the resulting effect on gas exchange in the maxillary sinus, by using computational fluid dynamics in two nasal cavity models: one with a preserved uncinate process, and the other with the uncinate process removed virtually. Uncinectomy distinctively changed the local flow topology by triggering the formation of counter-rotating vortices in the ostiomeatal complex, except for the instants with relatively low airflow rate when the respiration phase changed, ultimately leading to a change in the velocity field inside the ostium and maxillary sinus. Despite a significant increase in the maximum air velocity through the maxillary ostium, ventilation was found to increase only slightly when the uncinate process was removed. Furthermore, the degree of maxillary sinus ventilation by inhaled air was comparable to that by exhaled air. This was true to both models and was independent of the presence of the uncinate process. PMID- 26996069 TI - Adaptive immunity in the liver. AB - The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver. PMID- 26996077 TI - Reprogramming: Your contacts reveal your past. PMID- 26996078 TI - Genetic testing: Clinical sequencing right on target. PMID- 26996076 TI - Translating RNA sequencing into clinical diagnostics: opportunities and challenges. AB - With the emergence of RNA sequencing (RNA-seq) technologies, RNA-based biomolecules hold expanded promise for their diagnostic, prognostic and therapeutic applicability in various diseases, including cancers and infectious diseases. Detection of gene fusions and differential expression of known disease causing transcripts by RNA-seq represent some of the most immediate opportunities. However, it is the diversity of RNA species detected through RNA seq that holds new promise for the multi-faceted clinical applicability of RNA based measures, including the potential of extracellular RNAs as non-invasive diagnostic indicators of disease. Ongoing efforts towards the establishment of benchmark standards, assay optimization for clinical conditions and demonstration of assay reproducibility are required to expand the clinical utility of RNA-seq. PMID- 26996079 TI - A novel sibling-based design to quantify genetic and shared environmental effects: application to drug abuse, alcohol use disorder and criminal behavior. AB - BACKGROUND: Twin studies have been criticized for upwardly biased estimates that might contribute to the missing heritability problem. METHOD: We identified, from the general Swedish population born 1960-1990, informative sibships containing a proband, one reared-together full- or half-sibling and a full-, step- or half sibling with varying degrees of childhood cohabitation with the proband. Estimates of genetic, shared and individual specific environment for drug abuse (DA), alcohol use disorder (AUD) and criminal behavior (CB), assessed from medical, legal or pharmacy registries, were obtained using Mplus. RESULTS: Aggregate estimates of additive genetic effects for DA, AUD and CB obtained separately in males and females varied from 0.46 to 0.73 and agreed with those obtained from monozygotic and dizygotic twins from the same population. Of 54 heritability estimates from individual classes of informative sibling trios (3 syndromes * 9 classes of trios * 2 sexes), heritability estimates from the siblings were lower, tied and higher than those from obtained from twins in 26, one and 27 comparisons, respectively. By contrast, of 54 shared environmental estimates, 33 were lower than those found in twins, one tied and 20 were higher. CONCLUSIONS: With adequate information, human populations can provide many methods for estimating genetic and shared environmental effects. For the three externalizing syndromes examined, concerns that heritability estimates from twin studies are upwardly biased or were not generalizable to more typical kinds of siblings were not supported. Overestimation of heritability from twin studies is not a likely explanation for the missing heritability problem. PMID- 26996080 TI - Design, Synthesis, and Biological Evaluation of 6-(2-Amino-substituted phenyl)-4 (substituted phenyl)-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Anticonvulsant Agents. AB - As per structural requirement essential for anticonvulsant activity, a series of new 6-(2-amino-substituted phenyl)-4-(substituted phenyl)-1,2,4-triazine-3,5 dione derivatives were designed and synthesized. All the synthesized title derivatives were assessed for in vivo anticonvulsant screening by the two most employed standard animal seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizures, along with minimal motor impairment screening by rotarod test. Among all the synthesized compounds, the compound 4r showed excellent anticonvulsant activity with neither signs of neurotoxicity in the minimal motor impairment test nor signs of hepatotoxicity in the serum enzyme activity assay. The in silico studies of these title compounds were carried out for estimation of a pharmacophore pattern and the prediction of pharmacokinetic properties. To know the exact mechanism of our title compounds, a molecular docking study was carried out on the homology model of sodium ion (Na(+) ) channel and GABAA receptors. The results of the docking study as well as the in vitro study on both the receptors showed that our target compounds best act through the GABAA receptor rather than the Na(+) channel receptors. Additionally, GABA enzyme estimation was performed for further confirmation of the mechanism involved in its anticonvulsant activity. Conclusively, the compound 4r presents a novel scaffold in the search for safer and efficient anticonvulsants having neuroprotective as well as GABAergic effects. PMID- 26996081 TI - Involvement of Ca(2+)-Dependent Hyperpolarization in Sleep Duration in Mammals. AB - The detailed molecular mechanisms underlying the regulation of sleep duration in mammals are still elusive. To address this challenge, we constructed a simple computational model, which recapitulates the electrophysiological characteristics of the slow-wave sleep and awake states. Comprehensive bifurcation analysis predicted that a Ca(2+)-dependent hyperpolarization pathway may play a role in slow-wave sleep and hence in the regulation of sleep duration. To experimentally validate the prediction, we generate and analyze 21 KO mice. Here we found that impaired Ca(2+)-dependent K(+) channels (Kcnn2 and Kcnn3), voltage-gated Ca(2+) channels (Cacna1g and Cacna1h), or Ca(2+)/calmodulin-dependent kinases (Camk2a and Camk2b) decrease sleep duration, while impaired plasma membrane Ca(2+) ATPase (Atp2b3) increases sleep duration. Pharmacological intervention and whole-brain imaging validated that impaired NMDA receptors reduce sleep duration and directly increase the excitability of cells. Based on these results, we propose a hypothesis that a Ca(2+)-dependent hyperpolarization pathway underlies the regulation of sleep duration in mammals. PMID- 26996082 TI - Unmasking Latent Inhibitory Connections in Human Cortex to Reveal Dormant Cortical Memories. AB - Balance of cortical excitation and inhibition (EI) is thought to be disrupted in several neuropsychiatric conditions, yet it is not clear how it is maintained in the healthy human brain. When EI balance is disturbed during learning and memory in animal models, it can be restabilized via formation of inhibitory replicas of newly formed excitatory connections. Here we assess evidence for such selective inhibitory rebalancing in humans. Using fMRI repetition suppression we measure newly formed cortical associations in the human brain. We show that expression of these associations reduces over time despite persistence in behavior, consistent with inhibitory rebalancing. To test this, we modulated excitation/inhibition balance with transcranial direct current stimulation (tDCS). Using ultra-high field (7T) MRI and spectroscopy, we show that reducing GABA allows cortical associations to be re-expressed. This suggests that in humans associative memories are stored in balanced excitatory-inhibitory ensembles that lie dormant unless latent inhibitory connections are unmasked. PMID- 26996083 TI - Segregated Glycine-Glutamate Co-transmission from vGluT3 Amacrine Cells to Contrast-Suppressed and Contrast-Enhanced Retinal Circuits. AB - Since the introduction of Dale's principle of "one neuron releases one transmitter at all its synapses," a growing number of exceptions to this principle have been identified. While the concept of neurotransmitter co-release by a single neuron is now well accepted, the specific synaptic circuitry and functional advantage of co-neurotransmission remain poorly understood in general. Here we report Ca(2+)-dependent co-release of a new combination of inhibitory and excitatory neurotransmitters, namely, glycine and glutamate, by the vGluT3 expressing amacrine cell (GAC) in the mouse retina. GACs selectively make glycinergic synapses with uniformity detectors (UDs) and provide a major inhibitory drive that underlies the suppressed-by-contrast trigger feature of UDs. Meanwhile, GACs release glutamate to excite OFF alpha ganglion cells and a few other nonlinear, contrast-sensitive ganglion cells. This coordinated inhibition and excitation of two separate neuronal circuits by a single interneuron suggests a unique advantage in differential detection of visual field uniformity and contrast. PMID- 26996085 TI - The role of phosphorus, magnesium and potassium availability in soil fungal exploration of mineral nutrient sources in Norway spruce forests. AB - We investigated fungal growth and community composition in buried meshbags, amended with apatite, biotite or hornblende, in Norway spruce (Picea abies) forests of varying nutrient status. Norway spruce needles and soil collected from forests overlying serpentinite had low levels of potassium and phosphorus, those from granite had low levels of magnesium, whereas those from amphibolite had comparably high levels of these nutrients. We assayed the fungal colonization of meshbags by measuring ergosterol content and fungal community with 454 sequencing of the internal transcribed spacer region. In addition, we measured fine root density. Fungal biomass was increased by apatite amendment across all plots and particularly on the K- and P-deficient serpentinite plots, whereas hornblende and biotite had no effect on fungal biomass on any plots. Fungal community (total fungal and ectomycorrhizal) composition was affected strongly by sampling location and soil depth, whereas mineral amendments had no effect on community composition. Fine root biomass was significantly correlated with fungal biomass. Ectomycorrhizal communities may respond to increased host-tree phosphorus demand by increased colonization of phosphorus-containing minerals, but this does not appear to translate to a shift in ectomycorrhizal community composition. This growth response to nutrient demand does not appear to exist for potassium or magnesium limitation. PMID- 26996086 TI - Rigid sigmoidoscopy: no contamination of the sigmoidoscopist's face with faecal flora in a small study. PMID- 26996084 TI - Gamma and Beta Bursts Underlie Working Memory. AB - Working memory is thought to result from sustained neuron spiking. However, computational models suggest complex dynamics with discrete oscillatory bursts. We analyzed local field potential (LFP) and spiking from the prefrontal cortex (PFC) of monkeys performing a working memory task. There were brief bursts of narrow-band gamma oscillations (45-100 Hz), varied in time and frequency, accompanying encoding and re-activation of sensory information. They appeared at a minority of recording sites associated with spiking reflecting the to-be remembered items. Beta oscillations (20-35 Hz) also occurred in brief, variable bursts but reflected a default state interrupted by encoding and decoding. Only activity of neurons reflecting encoding/decoding correlated with changes in gamma burst rate. Thus, gamma bursts could gate access to, and prevent sensory interference with, working memory. This supports the hypothesis that working memory is manifested by discrete oscillatory dynamics and spiking, not sustained activity. PMID- 26996087 TI - Malnutrition and healthcare-acquired infections: the need for policy change in an evolving healthcare landscape. PMID- 26996088 TI - Qualitative study of views and experiences of performance management for healthcare-associated infections. AB - BACKGROUND: Centrally led performance management regimes using standard setting, monitoring, and incentives have become a prominent feature of infection prevention and control (IPC) in health systems. AIM: To characterize views and experiences of regulation and performance management relating to IPC in English hospitals. METHODS: Two qualitative datasets containing 139 interviews with healthcare workers and managers were analysed. Data directly relevant to performance management and IPC were extracted. Data analysis was based on the constant comparative method. FINDINGS: Participants reported that performance management regimes had mobilized action around specific infections. The benefits of establishing organizational structures of accountability were seen in empirical evidence of decreasing infection rates. Performance management was not, however, experienced as wholly benign, and setting targets in one area was seen to involve risks of 'tunnel vision' and the marginalization of other potentially important issues. Financial sanctions were viewed especially negatively; performance management was associated with risks of creating a culture of fearfulness, suppressing learning and disrupting inter-professional relationships. CONCLUSION: Centrally led performance management may have some important roles in IPC, but identifying where it is appropriate and determining its limits is critical. Persisting with harsh regimes may affect relationships and increase resistance to continued improvement efforts, but leaving all improvement to local teams may also be a flawed strategy. PMID- 26996089 TI - Systematic review of outbreaks of Pneumocystis jirovecii pneumonia: evidence that P. jirovecii is a transmissible organism and the implications for healthcare infection control. AB - BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Several nosocomial outbreaks of PCP have been reported in human-immunodeficiency-virus-negative, immunocompromised patients. The primary route of P. jirovecii transmission has yet to be proven; however, these outbreaks of infection suggest either interhuman transmission or a common environmental source. AIM: To identify and evaluate all published clusters and outbreaks of PCP. The main objective was to compare the epidemiology of the outbreaks, with a particular focus on the evidence for different modes of transmission. METHODS: PubMed and EMBASE were searched to identify all English-language articles describing PCP outbreaks or clusters between 1980 and March 2015. Data were extracted on the outbreak setting, features of the outbreak, application of molecular typing, results of epidemiological assessment and environmental sampling. FINDINGS: Thirty outbreaks described in 29 articles were identified. Twenty-five (83%) of these outbreaks were described in patients who had undergone solid organ transplantation, primarily renal transplantation. All studies described a defined cohort of patients who shared some nosocomial facilities, including both inpatient and outpatient areas. Genotyping was undertaken in 16 (47%) studies. Cases with an identical genotype were demonstrated in all these studies. CONCLUSIONS: The findings of this review raise a number of concerns regarding the public health and infection control implications of infection with PCP. The evidence presented for nosocomial acquisition and possible person-to-person transmission of infection suggests the need for formal infection control policies. PMID- 26996090 TI - Nano-TiO2-based photocatalytic disinfection of environmental surfaces contaminated by meticillin-resistant Staphylococcus aureus. AB - BACKGROUND: Traditional cleaning and disinfection methods are inefficient for complete decontamination of hospital surfaces from meticillin-resistant Staphylococcus aureus (MRSA). Additional methods, such as nano-TiO2-based photocatalytic disinfection (PCD), could be helpful. AIM: To evaluate anti-MRSA activity of PCD on polyvinyl chloride (PVC) surfaces in natural-like conditions. METHODS: Two identical PVC surfaces were used, and nano-TiO2 was incorporated into one of them. The surfaces were contaminated with MRSA isolated from hospitalized patients using a mist sprayer to simulate the mode of environmental contamination caused by a carrier. MRSA cell density was assessed before contamination until 180min after contamination using Rodac plates. The differences between test and control surfaces in terms of MRSA density and log MRSA density reduction were assessed using parametric and non-parametric statistical tests. Five strains were tested, and each strain was tested five times. FINDINGS: The highest median MRSA densities [46.3 and 43.1 colony-forming units (cfu)/cm(2) for control and test surfaces, respectively] were detected 45min after contamination. Median MRSA densities 180min after contamination were 10.1 and 0.7cfu/cm(2) for control and test surfaces, respectively (P<0.01). Log MRSA density reduction attributable to PCD was 1.16logcfu/cm(2), corresponding to 93% reduction of the baseline MRSA contamination. CONCLUSIONS: The disinfectant activity remained stable throughout the 25 testing occasions, despite between test cleaning and disinfection. The anti-MRSA activity of PCD was compatible with the benchmark for surface hygiene in hospitals (<1cfu/cm(2)), but required 3h of exposure to photocatalysis. Thus, PCD could be considered for non-clinical surfaces. However, for clinical surfaces, PCD should be regarded as supplemental to conventional decontamination procedures, rather than an alternative. PMID- 26996091 TI - Role of parents in the promotion of hand hygiene in the paediatric setting: a systematic literature review. AB - BACKGROUND: When a child is hospitalized, parents have to share their role to protect the child with the hospital, and establish a partnership with healthcare workers to deliver safe care to the child, including undertaking good hand hygiene practices. AIM: To review the scientific evidence about the participation of parents in the promotion of hand hygiene in paediatric settings. METHODS: A systematic search of MEDLINE, EMBASE and SciELO databases was undertaken using the following terms: ('hand hygiene'[MeSH] OR 'hand hygiene' OR 'hand disinfection'[MeSH] OR hand disinf* OR hand wash* OR handwash* OR hand antisep*) AND (parent OR caregiver OR mother OR father OR family OR families OR relatives). The Integrated Quality Criteria for Review of Multiple Study Designs tool was used for quality assessment. FINDINGS: The literature search yielded 1645 articles, and 11 studies met the inclusion criteria for the final analysis. Most studies were observational, and were based on questionnaires or interviews. Most parents had little knowledge about the indications to perform hand hygiene, but recognized hand hygiene as a relevant tool for the prevention of healthcare associated infections. Their willingness to remind healthcare workers about a failed opportunity to perform hand hygiene was variable and, overall, rather low. Parents felt more comfortable about reminding healthcare workers about hand hygiene if they had previously been invited to do so. CONCLUSIONS: Literature on the subject is scarce. The promotion of hand hygiene by parents should be further explored by research as a potential intervention for enhancing patient safety in paediatric settings. PMID- 26996092 TI - Combined infection training: a perspective from Ireland. PMID- 26996093 TI - Inpatient rehabilitation improves functional capacity, peripheral muscle strength and quality of life in patients with community-acquired pneumonia: a randomised trial. AB - QUESTION: Among people who are hospitalised for community-acquired pneumonia, does an inpatient exercise-based rehabilitation program improve functional outcomes, symptoms, quality of life and length of hospital stay more than a respiratory physiotherapy regimen? DESIGN: Randomised trial with concealed allocation, intention-to-treat analysis and blinding of some outcomes. PARTICIPANTS: Forty-nine adults hospitalised for community-acquired pneumonia. INTERVENTION: The experimental group (n=32) underwent a physical training program that included warm-up, stretching, peripheral muscle strength training and walking at a controlled speed for 15 minutes. The control group (n=17) underwent a respiratory physiotherapy regimen that included percussion, vibrocompression, respiratory exercises and free walking. The intervention regimens lasted 8 days. OUTCOME MEASURES: The primary outcome was the Glittre Activities of Daily Living test, which assesses the time taken to complete a series of functional tasks (eg, rising from a chair, walking, stairs, lifting and bending). Secondary outcomes were distance walked in the incremental shuttle walk test, peripheral muscle strength, quality of life, dyspnoea, lung function, C-reactive protein and length of hospital stay. Measures were taken 1 day before and 1 day after the intervention period. RESULTS: There was greater improvement in the experimental group than in the control group on the Glittre Activities of Daily Living test (mean between-group difference 39 seconds, 95% CI 20 to 59) and the incremental shuttle walk test (mean between-group difference 130 m, 95% CI 77 to 182). There were also significantly greater improvements in quality of life, dyspnoea and peripheral muscle strength in the experimental group than in the control group. There were no between-group differences in lung function, C-reactive protein or length of hospital stay. CONCLUSION: The improvement in functional outcomes after an inpatient rehabilitation program was greater than the improvement after standard respiratory physiotherapy. The exercise training program led to greater benefits in functional capacity, peripheral muscle strength, dyspnoea and quality of life. REGISTRATION: ClinicalTrials.gov, NCT02103400. PMID- 26996094 TI - A supervised exercise program may not add any benefit over advice for patients recovering from ankle fracture. PMID- 26996095 TI - The TIDieR checklist will benefit the physiotherapy profession. PMID- 26996098 TI - Moderate-intensity exercise reduces fatigue and improves mobility in cancer survivors: a systematic review and meta-regression. AB - QUESTION: Is there a dose-response effect of exercise on inflammation, fatigue and activity in cancer survivors? DESIGN: Systematic review with meta-regression analysis of randomised trials. PARTICIPANTS: Adults diagnosed with cancer, regardless of specific diagnosis or treatment. INTERVENTION: Exercise interventions including aerobic and/or resistance as a key component. OUTCOME MEASURES: The primary outcome measures were markers of inflammation (including C reactive protein and interleukins) and various measures of fatigue. The secondary outcomes were: measures of activity, as defined by the World Health Organization's International Classification of Functioning, Disability and Health, including activities of daily living and measures of functional mobility (eg, 6-minute walk test, timed sit-to-stand and stair-climb tests). Risk of bias was evaluated using the PEDro scale, and overall quality of evidence was assessed using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Forty-two trials involving 3816 participants were included. There was very low-quality to moderate-quality evidence that exercise results in significant reductions in fatigue (SMD 0.32, 95% CI 0.13 to 0.52) and increased walking endurance (SMD 0.77, 95% CI 0.26 to 1.28). A significant negative association was found between aerobic exercise intensity and fatigue reduction. A peak effect was found for moderate-intensity aerobic exercise for improving walking endurance. No dose-response relationship was found between exercise and markers of inflammation or exercise duration and outcomes. Rates of adherence were typically high and few adverse events were reported. CONCLUSIONS: Exercise is safe, reduces fatigue and increases endurance in cancer survivors. The results support the recommendation of prescribing moderate-intensity aerobic exercise to reduce fatigue and improve activity in people with cancer. REVIEW REGISTRATION: PROSPERO CRD42015019164. PMID- 26996096 TI - Implementation of a guideline-based clinical pathway of care to improve health outcomes following whiplash injury (Whiplash ImPaCT): protocol of a randomised, controlled trial. AB - INTRODUCTION: Whiplash-associated disorders (WAD) are a huge worldwide health and economic burden. The propensity towards developing into chronic, disabling conditions drives the rise in health and economic costs associated with treatment, productivity loss and compulsory third party insurance claims. Current treatments fail to address the well-documented heterogeneity of WAD and often result in poor outcomes. A novel approach is to evaluate whether the care provided according to the estimated risk of poor prognosis improves health outcomes while remaining cost-effective. RESEARCH QUESTIONS: (1) Does a guideline based clinical pathway of care improve health outcomes after whiplash injury compared to usual care? (2) Does risk of recovery have a differential effect on health outcomes for the clinical pathway of care? (3) Is the clinical pathway of care intervention cost-effective? (4) What are the variations in professional practice between usual care and the clinical pathway of care? DESIGN: Multi centre, randomised, controlled trial conducted over two Australian states: Queensland and New South Wales. PARTICIPANTS AND SETTING: 236 people with WAD (grade I-III, within 6 weeks of injury) and their primary healthcare providers. INTERVENTION: A clinical pathway of care, with care matched to the predicted risk of poor recovery. Participants at low risk of ongoing pain and disability (hence, predicted to fully recover) will receive up to three sessions of guideline-based advice and exercise with their primary healthcare provider. Participants at medium/high risk of developing ongoing pain and disability will be referred to a specialist (defined as a practitioner with expertise in whiplash) who will conduct a more in-depth physical and psychological assessment. As a result, the specialist will liaise with the original primary healthcare provider and determine one of three further pathways of care. CONTROL: Usual care provided by the primary healthcare provider that is based on clinical judgment. MEASUREMENTS: Primary (global rating of change and neck-related disability) and secondary (self efficacy, pain intensity, general health and disability and psychological health) outcomes will be collected using validated scales. Direct (eg, professional care, transportation costs, time spent for care, co-payments) and indirect (eg, lost economic productivity) costs will be obtained through an electronic cost diary. Health and cost outcomes will be assessed at baseline, 3, 6 and 12 months after randomisation. Professional practice outcomes will be evaluated through questionnaires completed by healthcare providers and their patients at 3 months. PROCEDURE: Potential participants (patients) will be identified through emergency departments, primary health clinics and advertisements. Eligible participants will complete baseline assessments and will be categorised into low or medium/high risk of poor recovery using a clinical prediction rule. After this assessment, participants will be randomly allocated to either a control group (n=118) or intervention group (n=118), stratified by risk subgroup and treatment site. The participants' nominated primary healthcare providers will be informed of their involvement in the trial. Consent will be obtained from the primary healthcare providers to participate and to obtain information about professional practice. Participants in the intervention group will additionally have access to an interactive website that provides information about whiplash and recovery relative to their risk category. ANALYSIS: Analysis will be conducted on an intention-to-treat basis. Outcomes will be analysed independently through cross sectional analyses using generalised linear models methods, with an appropriate link function, to test for an intervention effect, adjusted for the baseline values. The risk category will be tested for its association with treatment effect by adding risk group to the regression equation. Cost-effectiveness will be calculated using utility weights and the resulting measure will be cost per quality-adjusted life year (QALY) saved. Professional practice outcomes will be analysed using descriptive statistics. DISCUSSION: This research is significant as it will be the first study to address the heterogeneity of whiplash by implementing a clinical pathway of care that matches evidence-based interventions to projected risk of poor recovery. The results of this trial have the potential to change clinical practice for WAD, thereby maximising treatment effects, improving patient outcomes, reducing costs and maintaining the compulsory third party system. PMID- 26996099 TI - Exhaled gases online measurements for esophageal cancer patients and healthy people by proton transfer reaction mass spectrometry. AB - BACKGROUND: Esophageal cancer is a prevalent malignancy. There is a considerable demand for developing a fast and noninvasive method to screen out the suspect esophageal cancer patients who may undergo further clinical diagnosis. METHODS: The exhaled breathes from 29 esophageal cancer patients and 57 healthy people were directly measured using our home-made proton transfer reaction mass spectrometer (PTR-MS). Mann-Whitney U test and stepwise discriminant analysis were applied to identify the ions in the breath mass spectral data which can distinguish cancer cohort from healthy group. Receiver operating characteristics (ROC) analysis was also performed. RESULTS: Seven kinds of ions in the breath mass spectrum, viz., m/z 136, m/z 34, m/z 63, m/z 27, m/z 95, m/z 107 and m/z 45, have been found to distinguish between the esophageal cancer patients and healthy people with a sensitivity of 86.2% and a specificity of 89.5%, respectively. Compared with that from the healthy people, the breath mass spectra from esophageal cancer patients show that the mediant intensities of five kinds of ions were decrease and the rest two kinds of ions were increase. ROC analysis gave the area under the curve (AUC) of 0.943. CONCLUSIONS: This pilot study shows that the ionic characteristics of exhaled VOCs detected by PTR-MS may be used to differentiate between the esophageal cancer patients and the healthy people. Although the breath tests for more patients are needed to confirm such results, the present work indicates that the PTR-MS may be a promising method in the esophageal cancer screening. PMID- 26996100 TI - Maintenance hormonal and chemotherapy treatment in metastatic breast cancer: a systematic review. AB - Endocrine treatment is the first-line therapy in hormone-sensitive metastatic breast cancer while chemotherapy is the first option in tumors refractory to endocrine therapy and in hormone-negative disease. Optimal duration, efficacy and safety of a maintenance endocrine therapy or chemotherapy after an induction treatment are still a matter of debate. We performed a literature review to identify studies regarding maintenance hormonal and chemotherapy treatments in metastatic breast cancer. We analyzed data relating to efficacy (improvement of progression-free survival and overall survival) and safety (symptoms relief and quality of life [QoL]). Maintenance endocrine therapy could prolong progression free survival with a better control of symptoms and improving QoL. Maintenance chemotherapy prolong the response to a previous treatment, worsening the QoL, except for metronomic capecitabine. PMID- 26996102 TI - Support for the revocation of general safety test regulations in biologics license applications. AB - The United States Food and Drug Administration recently removed the requirement for a General Safety Test (GST) for biologics in the Code of Federal Regulations (21 CFR 610.11). The GST, as well as abnormal toxicity (European Pharmacopeia) and innocuity tests (World Health Organization), were designed to test for extraneous toxic contaminants on each product lot intended for human use. Tests require one-week observations for general health and weight following injection of specified volumes of product batches into guinea pigs and mice. At the volumes specified, dose-related toxicity may result when the product is pharmacologically active in rodents. With vaccines, required doses may be > 3 logs higher than intended human dose on a weight-adjusted basis and if an immune modulatory adjuvant is included, systemic immune hyperactivation may cause toxicity. Herein, using the CpG/alum adjuvant combination we evaluated the different test protocols and showed their unsuitability for this adjuvant combination. PMID- 26996101 TI - Muller glia reactivity follows retinal injury despite the absence of the glial fibrillary acidic protein gene in Xenopus. AB - Intermediate filament proteins are structural components of the cellular cytoskeleton with cell-type specific expression and function. Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein and is up regulated in glia of the nervous system in response to injury and during neurodegenerative diseases. In the retina, GFAP levels are dramatically increased in Muller glia and are thought to play a role in the extensive structural changes resulting in Muller cell hypertrophy and glial scar formation. In spite of similar changes to the morphology of Xenopus Muller cells following injury, we found that Xenopus lack a gfap gene. Other type III intermediate filament proteins were, however, significantly induced following rod photoreceptor ablation and retinal ganglion cell axotomy. The recently available X. tropicalis and X. laevis genomes indicate a small deletion most likely resulted in the loss of the gfap gene during anuran evolution. Lastly, a survey of representative species from all three extant amphibian orders including the Anura (frogs, toads), Caudata (salamanders, newts), and Gymnophiona (caecilians) suggests that deletion of the gfap locus occurred in the ancestor of all Anura after its divergence from the Caudata ancestor around 290 million years ago. Our results demonstrate that extensive changes in Muller cell morphology following retinal injury do not require GFAP in Xenopus, and other type III intermediate filament proteins may be involved in the gliotic response. PMID- 26996103 TI - A wearable biochemical sensor for monitoring alcohol consumption lifestyle through Ethyl glucuronide (EtG) detection in human sweat. AB - We demonstrate for the first time a wearable biochemical sensor for monitoring alcohol consumption through the detection and quantification of a metabolite of ethanol, ethyl glucuronide (EtG). We designed and fabricated two co-planar sensors with gold and zinc oxide as sensing electrodes. We also designed a LED based reporting for the presence of EtG in the human sweat samples. The sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for EtG were immobilized on the electrodes using thiol based chemistry. Detection of EtG from human sweat was achieved through chemiresistive sensing mechanism. In this method, an AC voltage was applied across the two coplanar electrodes and the impedance across the sensor electrodes was measured and calibrated for physiologically relevant doses of EtG in human sweat. EtG detection over a dose concentration of 0.001-100 MUg/L was demonstrated on both glass and polyimide substrates. Detection sensitivity was lower at 1 MUg/L with gold electrodes as compared to ZnO, which had detection sensitivity of 0.001 MUg/L. Based on the detection range the wearable sensor has the ability to detect alcohol consumption of up to 11 standard drinks in the US over a period of 4 to 9 hours. PMID- 26996104 TI - The conifer biomarkers dehydroabietic and abietic acids are widespread in Cyanobacteria. AB - Terpenes, a large family of natural products with important applications, are commonly associated with plants and fungi. The diterpenoids dehydroabietic and abietic acids are defense metabolites abundant in resin, and are used as biomarkers for conifer plants. We report here for the first time that the two diterpenoid acids are produced by members of several genera of cyanobacteria. Dehydroabietic acid was isolated from two cyanobacterial strains and its identity was confirmed spectroscopically. One or both of the diterpenoids were detected in the cells of phylogenetically diverse cyanobacteria belonging to four cyanobacterial 'botanical orders', from marine, estuarine and inland environments. Dehydroabietic acid was additionally found in culture supernatants. We investigated the natural role of the two resin acids in cyanobacteria using ecologically-relevant bioassays and found that the compounds inhibited the growth of a small coccoid cyanobacterium. The unexpected discovery of dehydroabietic and abietic acids in a wide range of cyanobacteria has implications for their use as plant biomarkers. PMID- 26996105 TI - Causes of death in childhood-onset Type 1 diabetes: long-term follow-up. AB - AIMS: To assess the causes of death and cause-specific standardized mortality ratios in two nationwide, population-based cohorts diagnosed with Type 1 diabetes during the periods 1973-1982 and 1989-2012, and to evaluate changes in causes of death during the follow-up period. METHODS: People with Type 1 diabetes who were aged < 15 years at diagnosis were identified in the Norwegian Childhood Diabetes Registry and followed from diagnosis until death, emigration or September 2013 (n = 7871). We assessed causes of death by linking data to the nationwide Cause of Death Registry and through a review committee that evaluated medical records, autopsy reports and death certificates. RESULTS: During a mean (range) follow-up of 16.8 (0-40.7) years, 241 individuals (3.1%) died, representing 132 143 person years. The leading cause of death before the age of 30 years was acute complications (41/119, 34.5%). After the age of 30 years cardiovascular disease was predominant (41/122, 33.6%), although death attributable to acute complications was still important in this age group (22/122, 18.0%). A total of 5% of deaths were caused by 'dead-in-bed' syndrome. The standardized mortality ratio was elevated for cardiovascular disease [11.9 (95% CI 8.6-16.4)] and violent death [1.7 (95% CI 1.3-2.1)] in both sexes combined, but was elevated for suicide only in women [2.5 (95% CI 1.2-5.3)]. The risk of death from acute complications was approximately half in women compared with men [hazard ratio 0.43 (95% CI 0.25-0.76)], and did not change with more recent year of diagnosis [hazard ratio 1.02 (0.98-1.05)]. CONCLUSIONS: There was no change in mortality attributable to acute complications during the study period. To reduce premature mortality in people with childhood-onset diabetes focus should be on prevention of acute complications. Male gender implied increased risk. PMID- 26996106 TI - Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis. AB - Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis. PMID- 26996107 TI - Effect of Vitamin A Supplementation on fatigue and depression in Multiple Sclerosis patients: A Double-Blind Placebo-Controlled Clinical Trial. AB - Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms. PMID- 26996108 TI - Increase in mRNA Level of Orexin1 and 2 Receptors Following Induction of Experimental Autoimmune Encephalomyelitis in Mice. AB - Orexin A and B are hypothalamic peptides with a wide variety of effects such as anti-inflammation and neuroprotection. Impaired function of orexin system has been reported in some neurodegenerative diseases like Parkinson, Huntington and Alzheimer. In this study, the mRNA expression levels of some hypothalamic peptides were investigated in C57BL/6 female mice with experimental autoimmune encephalomyelitis (EAE). Animals were randomly divided into two control and EAE groups. EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG) with complete Ferund's adjuvant and pertussis toxin. Twenty-first days following immunization, mice were decapitated to remove the brains. Then, the expression profiles of prepro-orexin, orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) in hypothalamic region were assessed using real-time PCR method. In this study, we found a considerable increase in the mRNA expression of OX1R and OX2R following EAE induction in C57BL/6 mice. Elevation levels of OX1R and OX2R following EAE induction suggest that alteration in orexinergic system may involve in pathogenesis of multiple sclerosis. PMID- 26996109 TI - Analysis of Killer Cell Immunoglobulin-like Receptor Genes and Their HLA Ligands in Iranian Patients with Ankylosing Spondylitis. AB - Ankylosing Spondylitis (AS) is a chronic rheumatic disease which mainly involves the axial skeleton. It seems that non-HLA genes, as well as HLA-B27 gene, are linked to the etiology of the disease. Recently, it has been documented that KIRs and their HLA ligands are contributed to the Ankylosing Spondylitis. The aim of this study was to evaluate the KIR genes and their HLA ligands in Iranian AS patients and healthy individuals. The present study includes 200 AS patient samples and 200 healthy control samples. KIR genotyping was performed using the polymerase chain reaction sequence-specific primer (PCR-SSP) method to type the presence or absence of the 16 KIR genes, 6 known specific HLA class I ligands and also, two pseudogenes. Two KIR genes (KIR-2DL3 and KIR2DL5), and among the HLA ligands, two HLA ligands (HLA-C2Lys80 and HLA-B27) genes were significantly different between case and control groups. In addition, we found some interesting KIR/HLA compound genotypes, which were associated with AS susceptibility. Our results suggest that the AS patients present more activating and less inhibitory KIR genes with combination of their HLA ligands than healthy controls. Once the balance of signal transduction between activating and inhibitory receptors is disturbed, the ability of NK cells to identify and lyse the targets in immune responses will be compromised. Accordingly, imbalance of activating and inhibitory KIR genes by up-regulating the activation and losing the inhibition of KIRs signaling or combination of both might be one of the important factors which underlying the pathogenesis of AS. PMID- 26996110 TI - Expression Levels of Proinflammatory Cytokines and NLRP3 Inflammasome in an Experimental Model of Oxazolone-induced Colitis. AB - IL-1beta and IL-17A are two cytokines with strong proinflammatory activities and are now known to be involved in a number of chronic inflammatory disorders. High mobility group box 1 (HMGB1) is a nuclear protein regulating the expression of these proinflammatory cytokines. The NLRP3 inflammasome promotes the maturation of the IL-1beta and its activation has been shown as a critical mechanism in the pathogenesis of inflammatory bowel disease (IBD). However, underlying mechanisms to modulate their production in IBD are still unclear. The aim of this study was to investigate the expression levels of mRNA for the NLRP3 inflammasome, HMGB1 and proinflammatory cytokines, IL-1beta, IL-17A in the inflamed colon of rats with experimental oxazolone-induced colitis. Experiments were carried out on male wistar rats. IL-1beta, IL-17A, HMGB1 and NLRP3 inflammasome mRNA expression were analyzed by real-time reverse transcriptase-polymerase chain reaction. Our results indicated that the expression levels of IL-1beta, IL-17A, NLRP3 and HMGB1 were elevated in the inflamed colon of rats with oxazolone-induced colitis. PMID- 26996111 TI - Association between TNFAIP3 Gene Polymorphisms and Risk of Allergic Rhinitis in a Chinese Han Population. AB - Tumor necrosis factor alpha-inducible protein 3 (TNFAIP3) gene polymorphisms have been reported to be associated with the susceptibility to several immune-related diseases. Here we investigated the effect of TNFAIP3 gene polymorphisms on the risk of allergic rhinitis (AR) in a Chinese Han population. The case-control study included 540 AR patients and 524 healthy controls. Genotyping for TNFAIP3 polymorphisms (rs5029928, rs9494885, rs10499194, rs610604, and rs7753873) were performed using restriction fragment length polymorphism analysis and DNA sequencing. Allele and genotype frequencies were compared between patients and controls. The rs9494885 TC genotype (corrected p (p=0.0032); odds ratio (OR)=2.06, 95% confidence intervals (CI): 1.40-3.04) and C allele (p=0.0056; OR=1.94, 95% CI: 1.35-2.76) were more frequent in AR patients compared with controls. The frequencies of the rs9494885 TT genotype (p=0.0029; OR=0.49, 95% CI: 0.33-0.72) and T allele (p= 0.0056; OR=0.52, 95% CI: 0.36-0.74) were lower in AR patients than that in controls. A higher frequency of the rs7753873 AC genotype (p=0.0023; OR=1.96, 95 %CI: 1.38-2.77) and C allele (p=0.0012; OR=1.74, 95% CI: 1.26-2.40) and a lower frequency of the rs7753873 AA genotype (p=0.0040; OR=0.53, 95% CI: 0.38-0.75) and A allele (p=0.0012; OR=0.58, 95% CI: 0.42-0.80) were observed in AR patients. TNFAIP3 gene polymorphisms (rs9494885 and rs7753873) are associated with the susceptibility to AR in the Chinese Han population. PMID- 26996112 TI - Peanut allergy in Mexican children: what is the effect of age at first consumption? AB - Studies suggest that children who start solid foods early are at risk for developing food allergies. Herein, we evaluated the effects of the introduction of peanuts to the diets of children on emerging peanut allergies. Children with allergic rhinitis and asthma were enrolled in the present study and evaluated in four stages. In the first stage, a clinical history was completed for all participants. In the second stage, skin tests were conducted to detect the sensitization to peanuts. In the third stage, the parents were interviewed about the peanut-eating habits of their children. In the fourth stage, children with a convincing history of allergy or a positive peanut skin test result were subjected to an open oral food challenge (OOFC). Three hundred children in four groups were included, 58.2% of the subjects were male, and the mean age was 7.3+/ 3.9 years. The median age of first exposure to peanuts in patients with peanut allergies was greater than that in children without peanut allergies (2 years versus 1 year; p=0.009). The multivariate analysis, including only those children subjected to the OOFC, revealed that the consumption of peanuts after the age of >=2 years is a risk factor for developing a peanut allergy (odds ratio=8.0, 95% confidence interval 1.3-50.0, p=0.026). The results of the present study showed that the late introduction of peanuts to children increases the risk of developing a peanut allergy. PMID- 26996113 TI - Association of TAP1 and TAP2 Gene Polymorphisms with Susceptibility to Pulmonary Tuberculosis. AB - TAP1 and TAP2 genes encode heterodimeric molecule involved in endogenous antigen processing. The present study was undertaken to find out the possible association between TAP1 and TAP2 polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Polymorphisms of TAP1 (rs1057141, rs1135216) and TAP2 (rs2228396, rs241447, rs67511411, rs141555015) were determined in 173 PTB patients and 164 healthy subjects. Our findings showed that rs1135216 AG, GG and AG+GG genotypes increased the risk of PTB in comparison with AA (OR=2.36, 95%CI=1.47-3.79, p<0.001; OR=19.13, 95%CI=2.47-148.2, p<0.001 and OR=2.77, 95%CI=1.74-4.39, p<0.001, respectively). The rs1135216 G allele was associated with increased risk of PTB (OR=2.65, 95%CI=1.784-3.969, p<0.001). TAP2 rs241447 AG and AG+GG genotypes decreased the risk of PTB (OR=0.41, 95%CI=0.26-0.65, p<0.001; OR=0.54, 95%CI=0.35-0.85, respectively). No significant association was found between TAP1 (rs1057141), TAP2 (rs2228396, rs67511411, rs141555015) variants and PTB. In conclusion, our findings proposed that TAP gene polymorphisms might be associated with PTB susceptibility among patients in Zahedan, southeast Iran. PMID- 26996115 TI - Quantitative Evaluation of BAFF, HMGB1, TLR 4 AND TLR 7 Expression in Patients with Relapsing Remitting Multiple Sclerosis. AB - Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by a complex immune response. Because of the complex nature of MS pathogenesis, a panel of biomarkers derived from different platforms will be required to reflect disease-related alterations. Monitoring and evaluation of molecules associated with the pathogenesis of the disease would provide useful information on disease progression and therapeutic assessment. In view of this, we evaluated the mRNA expression levels of B-cell activating factor (BAFF), high mobility group box 1 (HMGB-1), Toll like receptor (TLR) 4 and TLR7 in MS. These molecules are implicated in the pathogenesis of MS; however, they havereceived little attention. PBMCs were isolated from whole blood of 84 Relapsing Remitting Multiple Sclerosis patients and 70 healthy controls. Relative quantitative RT-PCR was applied to quantify the transcriptional levels of the immune markers. The mRNA expression levels of TLR7 were significantly elevated in RRMS patients than healthy controls. Whereas, TLR4 expression was found to be significantly lower in the patients than control group. We found no difference analyzing the mRNA levels of BAFF and HMGB1. Our data highlights the immune marker correlates in RRMS patients. However, further in-depth studies are warranted to check for their reliability of biomarkers in autoimmune diseases such as MS. PMID- 26996114 TI - Mannose-binding Lectin Deficiency in Patients with a History of Recurrent Infections. AB - Mannose-binding lectin (MBL) is a protein of innate immune system that is involved in opsonization and complement activation. MBL deficiency is associated with predisposition to infectious diseases; however subnormal levels are also seen in healthy subjects. The aim of this study was to investigate the prevalence and clinical manifestation of MBL deficiency in patients with increased susceptibility to infection. We studied the MBL serum concentration of 104 patients with a history of recurrent and/or severe infections referred to Immunology, Asthma and Allergy Research Institute (IAARI) in order to evaluate the primary immunodeficiency (PID). The distribution of MBL deficiency in these patients and 593 healthy subjects of previous study were analyzed. The frequency of individuals with MBL deficiency was significantly higher in patients with recurrent and/or severe infections (13.5% [14/104]) compared with healthy subjects (4.7% [28/593]; p=0.001; OR 3.1, 95% CI 1.5-6.1). However, in 10.9% (7/64) of patients with recurrent infections without any immunodeficiency background, the MBL deficiency was detected. On the whole, our findings indicate an association between MBL deficiency and increased susceptibility to infections. PMID- 26996116 TI - Adverse Reaction to Omalizumab in Patients with Chronic Urticaria: Flare Up or Ineffectiveness? AB - Omalizumab is a recombinant humanized anti-Ig E monoclonal antibody used as the third line treatment of chronic spontaneous urticaria (CSU). We report four patients with severe antihistamine-resistant CSU, who developed angioedema, anaphylaxis and/or flare up of urticaria at different times following omalizumab therapy. PMID- 26996117 TI - Gene Expression Profiling of Toll-Like Receptor 4 and 5 in Peripheral Blood Mononuclear Cells in Rheumatic Disorders: Ankylosing Spondylitis and Rheumatoid Arthritis. AB - No Abstract. PMID- 26996118 TI - Reply to Kamtchum-Tatuene and Fogang. PMID- 26996119 TI - Electroencephalographic changes following a trigeminal nerve stimulation (TNS) protocol: Assessing a novel depression treatment. PMID- 26996120 TI - Pt/WO3/FTO memristive devices with recoverable pseudo-electroforming for time delay switches in neuromorphic computing. AB - A recoverable pseudo-electroforming process was discovered in Pt/WO3/FTO devices. Unlike conventional electroforming, which is usually destructive, pseudo electroforming can be recovered when the electrical stimulation is removed. Furthermore, the time-dependent recovery process can be tuned by diverse voltage pulses applied in pseudo-electroforming; therefore, the device can be used as a time-delay switch in memristor-based neuromorphic networks. This "volatile" electroforming process can be attributed to the high oxygen vacancy concentration in the fluorine-doped tin oxide (FTO) bottom electrode, which acts as a non blocking electrode in the resistive switching. PMID- 26996121 TI - Optical micromanipulation of nanoparticles and cells inside living zebrafish. AB - Regulation of biological processes is often based on physical interactions between cells and their microenvironment. To unravel how and where interactions occur, micromanipulation methods can be used that offer high-precision control over the duration, position and magnitude of interactions. However, lacking an in vivo system, micromanipulation has generally been done with cells in vitro, which may not reflect the complex in vivo situation inside multicellular organisms. Here using optical tweezers we demonstrate micromanipulation throughout the transparent zebrafish embryo. We show that different cells, as well as injected nanoparticles and bacteria can be trapped and that adhesion properties and membrane deformation of endothelium and macrophages can be analysed. This non invasive micromanipulation inside a whole-organism gives direct insights into cell interactions that are not accessible using existing approaches. Potential applications include screening of nanoparticle-cell interactions for cancer therapy or tissue invasion studies in cancer and infection biology. PMID- 26996122 TI - Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer. AB - The underglycosylated mucin 1 tumor antigen (uMUC1) is a biomarker that forecasts the progression of adenocarcinomas. In this study, we evaluated the utility of a dual-modality molecular imaging approach based on targeting uMUC1 for monitoring chemotherapeutic response in a transgenic murine model of pancreatic cancer (KCM triple transgenic mice). An uMUC1-specific contrast agent (MN-EPPT) was synthesized for use with magnetic resonance imaging (MRI) and fluorescence optical imaging. It consisted of dextran-coated iron oxide nanoparticles conjugated to the near infrared fluorescent dye Cy5.5 and to a uMUC1-specific peptide (EPPT). KCM triple transgenic mice were given gemcitabine as chemotherapy while control animals received saline injections following the same schedule. Changes in uMUC1 levels following chemotherapy were monitored using T2-weighted MRI and optical imaging before and 24 hr after injection of the MN-EPPT. uMUC1 expression in tumors from both groups was evaluated by histology and qRT-PCR. We observed that the average delta-T2 in the gemcitabine-treated group was significantly reduced compared to the control group indicating lower accumulation of MN-EPPT, and correspondingly, a lower level of uMUC1 expression. In vivo optical imaging confirmed the MRI findings. Fluorescence microscopy of pancreatic tumor sections showed a lower level of uMUC1 expression in the gemcitabine treated group compared to the control, which was confirmed by qRT-PCR. Our data proved that changes in uMUC1 expression after gemcitabine chemotherapy could be evaluated using MN-EPPT-enhanced in vivo MR and optical imaging. These results suggest that the uMUC1-targeted imaging approach could provide a useful tool for the predictive assessment of therapeutic response. PMID- 26996123 TI - Ticket to ride: export of proteins to the Plasmodium falciparum-infected erythrocyte. AB - The malaria parasite Plasmodium falciparum exports numerous proteins to its chosen host cell, the mature human erythrocyte. Many of these proteins are important for parasite survival. To reach the host cell, parasites must cross multiple membrane barriers and then furthermore be targeted to their correct sub cellular localisation. This novel transport pathway has received much research attention in the past decades, especially as many of the mechanisms are expected to be parasite-specific and thus potential targets for drug development. In this article we summarize some of the most recent advances in this field, and highlight areas in which further research is needed. PMID- 26996124 TI - Self-assembly of a 5-fluorouracil-dipeptide hydrogel. AB - The self-assembly of 5-fluorouracil dilysine conjugates into self-supporting hydrogels, comprised of entangled nanofibers or rigid nanotubes with diameters of 10 and 16 nm, respectively, is reported. The rate of release of 5-Fu from the conjugates was highly dependent on concentration in solution, whereas, release from the fully formed hydrogels was significantly slower. The 5-Fu conjugate also exhibited promising in vitro cytotoxicity against human tumor cell lines A549, H460 and H23. PMID- 26996125 TI - Differential expression patterns of MafB and c-Maf in macrophages in vivo and in vitro. AB - The large Maf transcription factors c-Maf and MafB are expressed in macrophage lineage hematopoietic cells, but the expression patterns of MafB and c-Maf in macrophage subtypes and tissue-resident macrophages have not been fully analyzed. First, we analyzed MafB and c-Maf protein expression in tissue-resident macrophages. Mouse lymph nodes, spleens, lungs, and kidneys were subjected to immunohistochemistry using anti-MafB and anti-c-Maf. Both MafB and c-Maf signals were observed in lymph node macrophages. In the splenic macrophages the MafB signal was detected by anti-MafB, but the c-Maf signal was not detected. No expression of c-Maf or MafB was detected in macrophages in the lung and kidney. Flow cytometry analysis revealed a similar pattern of GFP expression in Mafb/GFP knock-in heterozygous mice. To analyze these different expression patterns in greater detail, we examined the expression of MafB and c-Maf by quantitative RT PCR in different cytokine- or LPS-induced macrophages in vitro. MafB expression was induced by IL-10 or IL-4 with IL-13 and was reduced by LPS or GM-CSF. By contrast, c-Maf expression was induced by IL-10 and reduced by IL-4 with IL-13 or GM-CSF. These results indicate that MafB and c-Maf have different expression patterns in macrophages, suggesting differences in function. PMID- 26996126 TI - Cisplatin-induced apoptosis in non-small-cell lung cancer cells is dependent on Bax- and Bak-induction pathway and synergistically activated by BH3-mimetic ABT 263 in p53 wild-type and mutant cells. AB - Cisplatin is a highly effective anticancer drug for treatment of various tumors including non-small-cell lung cancer (NSCLC), and is especially useful in cases nonresponsive to molecular-targeted drugs. Accumulating evidence has shown that cisplatin activates the p53-dependent apoptotic pathway, but it also induces apoptosis in p53-mutated cancer cells. Here we demonstrated that DNA-damage inducible proapoptotic BH3 (Bcl-2 homology region 3)-only Bcl-2 family members, Noxa, Puma, Bim and Bid, are not involved in cisplatin-induced apoptosis in human NSCLC cell lines. In contrast, the expression of proapoptotic multidomain Bcl-2 family members, Bak and Bax, was induced by cisplatin in p53-dependent and independent manners, respectively. Moreover, in wild-type p53-expressing cells, cisplatin mainly used the Bak-dependent apoptotic pathway, but this apoptotic pathway shifted to the Bax-dependent pathway by loss-of-function of p53. Furthermore, both Bak- and Bax-induced apoptosis was enhanced by the antiapoptotic Bcl-2 family member, Bcl-XL knockdown, but not by Mcl-1 knockdown. From this result, we tested the effect of ABT-263 (Navitoclax), the specific inhibitor of Bcl-2 and Bcl-XL, but not Mcl-1, and found that ABT-263 synergistically enhanced cisplatin-induced apoptosis in NSCLC cells in the presence or absence of p53. These results indicate a novel regulatory system in cisplatin-induced NSCLC cell apoptosis, and a candidate efficient combination chemotherapy method against lung cancers. PMID- 26996128 TI - On the linkage between the ubiquitin-proteasome system and the mitochondria. AB - Several metabolic pathways critical for cellular homeostasis occur in the mitochondria. Because of the evolution of mitochondria and their physical separation, these pathways have traditionally been thought to be free from regulation by the ubiquitin-proteasome system. This perception has recently been challenged by evidence for the presence of ubiquitin system components in the mitochondria. Furthermore, it has been shown that certain mitochondrial proteins are conjugated by ubiquitin, and some of them are degraded by the proteasome. Of particular interest is the finding that some of these proteins are localized to the inner membrane and matrix, which rules out that their targeting is mediated by the cytosolic ubiquitin system. However, the extent of the involvement of the ubiquitin system in mitochondrial regulation is not known. The present study addresses this surprising finding, employing several independent approaches. First, we identified reported ubiquitin conjugates in human and yeast mitochondria and found that a large fraction of the mitochondrial proteome (62% in human) is ubiquitinated, with most proteins localized to the inner membrane and matrix. Next, we searched the literature and found that numerous ubiquitin system components localize to the mitochondria and/or contain mitochondrial targeting sequences. Finally, we identified reported protein-protein interactions between ubiquitin system components and mitochondrial proteins. These unexpected findings suggest that mitochondrial regulation by the ubiquitin system is fundamental and may have broad biomedical implications. PMID- 26996127 TI - Autophagy mediated TiAl6V4 particle-induced peri-implant osteolysis by promoting expression of TNF-alpha. AB - Peri-prosthetic osteolysis and the consequent aseptic loosening constitute the most common reason for total joint arthroplasty failure and surgical revision. Although numerous studies suggest that pro-inflammatory cytokines induced by wear particles is involved in the pathological process of aseptic loosening, the underlying mechanism linking wear particles to pro-inflammatory cytokines remains to be illustrated. In the present study, we investigated the effect of autophagy on TNF-alpha secretion induced by TiAl6V4 particles (TiPs) in macrophages and in a calvarial resorption animal model. Our study demonstrated that TiPs activated autophage in macrophages and particle-induced osteolysis animal models as well as periprosthetic membranes of patients with aseptic loosening. The autophagy inhibitor 3-MA (3-methyladenine) could dramatically reduce TiPs-induced TNF-alpha expression both in macrophages and in membranes from animal models. Furthermore, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Collectively, these results suggest that autophagy plays a key role in TiPs-induced osteolysis by promoting TNF-alpha expression and that blocking autophagy may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis. PMID- 26996129 TI - MiR-21a-5p suppresses bisphenol A-induced pre-adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK. AB - Childhood obesity is a metabolic disease characterized by accumulation of excessive fat. Bisphenol A (BPA), a potential obesogen compound, possesses an estrogen mimetic activity and endocrine disruption effect. MicroRNA-21a-5p (miR 21a-5p) is reported to regulate the adipogenic differentiation. Our study showed that miR-21a-5p overexpression significantly decreased the red lipid droplets and triglyceride level in BPA-induced 3T3-L1 cells. BPA induced the mRNA and protein expression levels of PPARgamma, C/EBPalpha and adiponectin, and the induction was inhibited by miR-21a-5p mimics transfection. MiR-21a-5p mimics inhibited the GR activity, GR phosphorylation (S220, S21a-5p2, and S234), and the activation of p38/MAPK pathway, which are elevated by BPA treatment in 3T3-L1 cells. MiR-21a-5p overexpression inhibited the protein level of MKK3, but not in the mRNA level. Luciferase activity assay showed that miR-21a-5p directly targeted map2k3 3'-UTR. MKK3 overexpression attenuated the effect of miR-21a-5p mimics transfection on 3T3-L1 differentiation. We also assessed the body weight, fat mass and the content of serum lipid in rats subcutaneous injected with BPA and miR-21a-5p mimics. MiR-21a-5p overexpression attenuated BPA-induced obesity in vivo. These findings suggested that miR-21a-5p inhibited BPA induced adipocyte differentiation by targeting map2k3 through MKK3/p38/MAPK in 3T3-L1 cells, providing a potential therapeutic strategy for BPA induced obesity. PMID- 26996130 TI - Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells. AB - Several recent studies have suggested that cancer stem cells (CSCs) are involved in resistance to gefitinib in non-small cell lung cancer (NSCLC). Oct4, a member of the POU-domain transcription factor family, has been shown to be involved in CSC properties of various cancers. We previously reported that Oct4 and the putative lung CSC marker CD133 were highly expressed in gefitinib-resistant persisters (GRPs) in NSCLC cells, and GRPs exhibited characteristic features of the CSCs phenotype. The aim of this study was to elucidate the role of Oct4 in the resistance to gefitinib in NSCLC cells with an activating epidermal growth factor receptor (EGFR) mutation. NSCLC cell lines, PC9, which express the EGFR exon 19 deletion mutation, were transplanted into NOG mice, and were treated with gefitinib in vivo. After 14-17 days of gefitinib treatment, the tumors still remained; these tumors were referred to as gefitinib-resistant tumors (GRTs). PC9 GRTs showed higher expression of Oct4 and CD133. To investigate the role of Oct4 in the maintenance of gefitinib-resistant lung CSCs, we introduced the Oct4 gene into PC9 and HCC827 cells carrying an activating EGFR mutation by lentiviral infection. Transfection of Oct4 significantly increased CD133-positive GRPs and the number of sphere formation, reflecting the self-renewal activity, of PC9 and HCC827 cells under the high concentration of gefitinib in vitro. Furthermore, Oct4-overexpressing PC9 cells (PC9-Oct4) significantly formed tumors at 1 * 10 cells/injection in NOG mice as compared to control cells. In addition, PC9-Oct4 tumors were more resistant to gefitinib treatment as compared to control cells in vivo. Finally, immunohistochemical analysis revealed that Oct4 was highly expressed in tumor specimens of EGFR-mutant NSCLC patients with acquired resistance to gefitinib. Collectively, these findings suggest that Oct4 plays a pivotal role in the maintenance of lung CSCs resistant to gefitinib in EGFR mutation-positive NSCLC. PMID- 26996131 TI - Functional characterisation of ADIPOQ variants using individuals recruited by genotype. AB - Four non-coding GWAS variants in or near the ADIPOQ gene (rs17300539, rs17366653, rs3821799 and rs56354395) together explain 4% of the variation in circulating adiponectin. The functional basis for this is unknown. We tested the effect of these variants on ADIPOQ transcription, splicing and stability respectively in adipose tissue samples from participants recruited by rs17366653 genotype. Transcripts carrying rs17300539 demonstrated a 17% increase in expression (p = 0.001). Variant rs17366653 was associated with disruption of ADIPOQ splicing leading to a 7 fold increase in levels of a non-functional transcript (p = 0.002). Transcripts carrying rs56354395 demonstrated a 59% decrease in expression (p = <0.0001). No effects of rs3821799 genotype on expression was observed. Association between variation in the ADIPOQ gene and serum adiponectin may arise from effects on mRNA transcription, splicing or stability. These studies illustrate the utility of recruit-by-genotype studies in relevant human tissues in functional interpretation of GWAS signals. PMID- 26996132 TI - Deferoxamine-mediated up-regulation of HIF-1alpha prevents dopaminergic neuronal death via the activation of MAPK family proteins in MPTP-treated mice. AB - Accumulating evidence suggests that an abnormal accumulation of iron in the substantia nigra (SN) is one of the defining characteristics of Parkinson's disease (PD). Accordingly, the potential neuroprotection of Fe chelators is widely acknowledged for the treatment of PD. Although desferrioxamine (DFO), an iron chelator widely used in clinical settings, has been reported to improve motor deficits and dopaminergic neuronal survival in animal models of PD, DFO has poor penetration to cross the blood-brain barrier and elicits side effects. We evaluated whether an intranasal administration of DFO improves the 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of dopaminergic neurons in the nigrostriatal axis and investigated the molecular mechanisms of intranasal DFO treatment in preventing MPTP-induced neurodegeneration. Treatment with DFO efficiently alleviated behavioral deficits, increased the survival of tyrosine hydroxylase (TH)-positive neurons, and decreased the action of astrocytes in the SN and striatum in an MPTP-induced PD mouse model. Interestingly, we found that DFO up-regulated the expression of HIF-1alpha protein, TH, vascular endothelial growth factor (VEGF), and growth associated protein 43 (GAP43) and down-regulated the expression of alpha-synuclein, divalent metal transporter with iron-responsive element (DMT1+IRE), and transferrin receptor (TFR). This was accompanied by a decrease in iron-positive cells in the SN and striatum of the DFO-treated group. We further revealed that DFO treatment significantly inhibited the MPTP-induced phosphorylation of the c-Jun N-terminal kinase (JNK) and differentially enhanced the phosphorylation of extracellular regulated protein kinases (ERK) and mitogen-activated protein kinase (MAPK)/P38 kinase. Additionally, the effects of DFO on increasing the Bcl-2/Bax ratio were further validated in vitro and in vivo. In SH-SY5Y cells, the DFO-mediated up regulation of HIF-1alpha occurred via the activation of the ERK and P38MAPK signaling pathway. Collectively, the present data suggest that intranasal DFO treatment is effective in reversing MPTP-induced brain abnormalities and that HIF 1-pathway activation is a potential therapy target for the attenuation of neurodegeneration. PMID- 26996134 TI - Hippocampal hyperexcitability in fetal alcohol spectrum disorder: Pathological sharp waves and excitatory/inhibitory synaptic imbalance. AB - Prenatal alcohol exposure (PAE) can lead to long-lasting neurological alterations that may predispose individuals to seizures and neurobehavioral dysfunction. To date, there exists limited information regarding the underlying pathophysiological mechanisms. The hippocampal CA3 region generates excitatory population activity, called sharp waves (SPWs), that provide an ideal model to study perturbations in neuronal excitability at the network and cellular levels. In the present study, we utilized a mouse model of PAE and used dual extracellular and whole-cell patch-clamp recordings from CA3 hippocampal pyramidal cells to evaluate the effect of 1st trimester-equivalent ethanol exposure (10% v/v) on SPW activity and excitatory/inhibitory balance. We observed that PAE significantly altered in vitro SPW waveforms, with an increased duration and amplitude, when compared to controls. In addition, PAE slices exhibited reduced pharmacological inhibition by the GABA-A receptor antagonist bicuculline (BMI) on SPW activity, and increased population spike paired-pulse ratios, all indicative of network disinhibition within the PAE hippocampus. Evaluation of PAE CA3 pyramidal cell activity associated with SPWs, revealed increased action potential cell firing, which was accompanied by an imbalance of excitatory/inhibitory synaptic drive, shifted in favor of excitation. Moreover, we observed intrinsic changes in CA3 pyramidal activity in PAE animals, including increased burst firing and instantaneous firing rate. This is the first study to provide evidence for hippocampal dysfunction in the ability to maintain network homeostasis and underlying cellular hyperexcitability in a model of PAE. These circuit and cellular level alterations may contribute to the increased propensity for seizures and neurobehavioral dysfunction observed in patients with a history of PAE. PMID- 26996133 TI - Models of axon regeneration in Drosophila. AB - Maintaining neuronal connectivity in the face of injury and disease is a major challenge for the nervous system. The great length of axons makes them particularly vulnerable to insult with dire consequences for neuronal function. In the peripheral nervous system there is a program of axonal regeneration that can reestablish connectivity. In the mammalian central nervous system, however, injured axons have little or no capacity to regenerate. The molecular mechanisms that promote axon regeneration have begun to be identified and many of the implicated pathways are evolutionarily conserved. Here we discuss Drosophila models of axonal regrowth, describe insights derived from these studies, and highlight future directions in the use of the fly for dissecting the mechanisms of axonal regeneration. PMID- 26996135 TI - Evaluation of the use of fluoroscopy guided needle biopsies for diagnosing cases of suspected pathological fractures. AB - AIM: Establishing an early and accurate diagnosis in cases of suspected pathological fractures is crucial to initiate optimal treatment without delay. The use of percutaneous biopsy has become popular over the past few years. However, there is a paucity of information regarding the efficacy and safety of percutaneous biopsy procedures guided by fluoroscopy. METHODS: A total of 137 percutaneous C-arm fluoroscopy-guided core needle biopsy (CNB) procedures were performed in 135 patients with suspected pathological fractures. The sensitivity, specificity, accuracy, and overall prognostic value of these procedures were evaluated. Complications, if any, were documented for all cases. RESULTS: The overall sensitivity, specificity, and accuracy were 82.0%, 100%, and 83.2%, respectively. The positive and negative predictive value was 100% and 28.1%, respectively. There were 23 "false negative" cases in our study, of which 15 were benign lesions and eight were malignant tumors. No "false-positives" were found. Major procedure-related complications occurred in three patients (2.2%). These complications, however, did not alter the prognosis of these patients. CONCLUSION: Percutaneous C-arm fluoroscopy-guided biopsy procedures are both effective and safe for diagnosis of suspected pathological fractures in the appendicular skeleton. PMID- 26996136 TI - A neutralization charge detection method for detecting ions under ambient and liquid-phase conditions. AB - The neutralization charge detection method detects induction signals produced from the neutralization of electric charges of ions at metal surfaces. The signals are intense and can propagate through phase boundaries for detection. The detection method can detect ions under ambient and liquid-phase conditions with high sensitivity and fast response time. PMID- 26996138 TI - Organometallic molecular wires as versatile modules for energy-level alignment of the metal-molecule-metal junction. AB - The organometallic Ru molecular wires 1-3 Ru(PR3)4(C[triple bond, length as m dash]CC5H5N)2 [(PR3)4 = (dppe)2 (1), [P(OMe3)]4 (2), and (dmpe)2 (3)] show significantly higher conductance compared to their organic counterpart, 1,4 dipyridyl butadiyne (4). CV and UV-Vis measurements and DFT calculations suggest that the high-lying HOMOs of the Ru wires are the key factor for the high conductance. PMID- 26996137 TI - Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers. AB - Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as "duro-repulsive" cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei. PMID- 26996140 TI - Haploidentical hematopoietic stem cell transplantation for paediatric high-risk T cell acute lymphoblastic leukaemia. AB - Paediatric HR T-cell ALL demonstrates dismal prognosis with chemotherapy, and poor outcomes could be improved with allo-SCT. HID-SCT is an almost immediately available choice; however, few studies have focused on the outcomes of HID-SCT for paediatric HR T-ALL. Forty-eight consecutive HR T-ALL children who underwent HID-SCT were included. Survival outcomes and factors predictive of outcomes were retrospectively analysed. Of the 48 patients, 35 were in CR1, 10 in CR2, and three in relapse. The cumulative incidence of grade 3/4 aGVHD was 10.4% and that of extensive cGVHD was 28.4%. The CIR at three yr was 30.8% and that of NRM at three yr was 14.7%. At a median follow-up of 20.0 (range 2.5-124.2) months, the three-yr LFS was 54.4%. Children who received transplants during CR1 had a better LFS (65.7% vs. 26.0%, p = 0.008) and a lower relapse rate (19.8% vs. 56.7%, p = 0.014) compared to those during non-CR1. HID-SCT is feasible for HR T-ALL children, and survival outcomes are better when performed in CR1 compared to non CR1. Prospective clinical trials would be needed to confirm that. PMID- 26996139 TI - Zika virus: History, emergence, biology, and prospects for control. AB - Zika virus (ZIKV), a previously obscure flavivirus closely related to dengue, West Nile, Japanese encephalitis and yellow fever viruses, has emerged explosively since 2007 to cause a series of epidemics in Micronesia, the South Pacific, and most recently the Americas. After its putative evolution in sub Saharan Africa, ZIKV spread in the distant past to Asia and has probably emerged on multiple occasions into urban transmission cycles involving Aedes (Stegomyia) spp. mosquitoes and human amplification hosts, accompanied by a relatively mild dengue-like illness. The unprecedented numbers of people infected during recent outbreaks in the South Pacific and the Americas may have resulted in enough ZIKV infections to notice relatively rare congenital microcephaly and Guillain-Barre syndromes. Another hypothesis is that phenotypic changes in Asian lineage ZIKV strains led to these disease outcomes. Here, we review potential strategies to control the ongoing outbreak through vector-centric approaches as well as the prospects for the development of vaccines and therapeutics. PMID- 26996141 TI - CrossTalk proposal: Intramyocellular ceramide accumulation does modulate insulin resistance. PMID- 26996142 TI - Fixation patterns, not clinical diagnosis, predict body size over-estimation in eating disordered women and healthy controls. AB - OBJECTIVE: A core feature of anorexia nervosa (AN) is an over-estimation of body size. Women with AN have a different pattern of eye-movements when judging bodies, but it is unclear whether this is specific to their diagnosis or whether it is found in anyone over-estimating body size. METHOD: To address this question, we compared the eye movement patterns from three participant groups while they carried out a body size estimation task: (i) 20 women with recovering/recovered anorexia (rAN) who had concerns about body shape and weight and who over-estimated body size, (ii) 20 healthy controls who had normative levels of concern about body shape and who estimated body size accurately (iii) 20 healthy controls who had normative levels of concern about body shape but who did over-estimate body size. RESULTS: Comparisons between the three groups showed that: (i) accurate body size estimators tended to look more in the waist region, and this was independent of clinical diagnosis; (ii) there is a pattern of looking at images of bodies, particularly viewing the upper parts of the torso and face, which is specific to participants with rAN but which is independent of accuracy in body size estimation. DISCUSSION: Since the over-estimating controls did not share the same body image concerns that women with rAN report, their over estimation cannot be explained by attitudinal concerns about body shape and weight. These results suggest that a distributed fixation pattern is associated with over-estimation of body size and should be addressed in treatment programs. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:507-518). PMID- 26996143 TI - The influence of birth season on mortality in the United States. AB - OBJECTIVES: Birth season is related to a variety of later outcomes. Among them, mortality is of great interest because it represents lifetime health outcomes. We examined the relationship between birth season and mortality in the US. METHODS: We merged the US National Health Interview Survey (NHIS) and NHIS public-use linked mortality files and analyzed 17,082 men and 19,075 women who were followed for 20 years from 1986 to 2006. We used the Cox proportional hazards model to relate birth quarter to mortality, controlling for birth year fixed effects. RESULTS: After controlling for years of schooling and birth year fixed effects, we found that, relative to men born in the first quarter, men born in the fourth quarter were 11% less likely to die. For women, the benefit was the largest for women born in the third quarter who were 14% less likely to die than women born in the first quarter. In the relationship between birth season and mortality, cardiovascular diseases played a noticeable role for men and malignant neoplasms for women. CONCLUSIONS: These results were consistent with those for some developed countries, but not entirely with those for contemporary developing countries and developed countries of the past. Simple mechanisms based on the perinatal environment cannot account for the inconsistent results. We suggest that family background may play some, but not an exhaustive, role in the relationship between birth season and mortality. Am. J. Hum. Biol. 28:662-670, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26996144 TI - Direct costs of interferon-based and interferon-free direct-acting antiviral regimens for the treatment of chronic hepatitis C infection. AB - Given the increasing budget impact of Hepatitis C virus (HCV) treatment, robust real-world cost data are essential for healthcare decision-makers to evaluate and understand the costs and benefits of these treatments. To determine the direct cost of treating HCV infection in a hospital-based ambulatory care setting in Ireland based on available data from the Irish national hepatitis C treatment registry. A microcosting study of the direct costs of patients with hepatitis C treated with interferon-based and interferon-free direct-acting antiviral regimens was conducted. Attendance at the outpatient clinic for clinical assessment, the quantity of resources used per patient, the medication prescribed and the identification and timing of staff involvement was measured and combined to establish a mean cost of treatment per patient and a cost per sustained virological response (SVR). One hundred and sixty-eight patients were included in the analysis; 119 treated with interferon-based direct-acting antiviral regimens and 47 treated with interferon-free regimens. The mean costs of treatment with the interferon-based regimens per patient were ?38 286 (95% CI ?35 305-?41 061). The cost per SVR was ?62 457. The mean cost of treatment with interferon-free regimens per patient was ?55 734 (95% CI ?50 906-?60 880). The cost per SVR was ?81 873. Real-world cost data provide valuable information to enhance reimbursement decisions. While the direct costs associated with hepatitis C treatment in Ireland are substantial, it is reasonable to expect that the mean cost of treatment and the cost per SVR will reduce as patients with less advanced disease are treated with interferon-free therapies. PMID- 26996146 TI - Global profiling of the gene expression and alternative splicing events during hypoxia-regulated chondrogenic differentiation in human cartilage endplate derived stem cells. AB - The intervertebral disc (IVD) degeneration is initiated by cartilage endplate (CEP) degeneration and is characterised by reduced chondrification. Cartilage endplate-derived stem cells (CESCs) with chondrogenic differentiation abilities are responsible for the restoration of cartilage. CEP remains in an avascular and hypoxic microenvironment. In this study, we observed that the physiological hypoxia greatly promotes the chondrogenic differentiation of CESCs. This tissue specificity of the differentiation fate of CESCs in response to the hypoxic microenvironment was physiologically significant for the CEP to maintain the chondrification status. To investigate the mechanisms underlying the hypoxia regulated chondrogenic differentiation of CESCs, we adopted a high-throughput scanning technology to detect the global profiling of gene expression and alternative splicing (AS) event changes during chondrogenic differentiation under hypoxia in CESCs compared to those induced under normoxia. An Affymetrix Human Transcriptome Array 2.0 was used to identify the differentially expressed genes (DEGs) and alternatively spliced genes (ASGs). After RT-PCR validation, GO and KEGG pathway analyses of both the DEGs and ASGs were performed. The enrichment of the GO functional terms and signalling pathways provided referential direction of the mechanism to study the gene expression and AS in the hypoxia-regulated chondrogenesis promotion, which could be helpful in understanding this physiological phenomenon, and it could also be instrumental in finding targets for CEP degeneration therapy. PMID- 26996145 TI - A two-component system regulates gene expression of the type IX secretion component proteins via an ECF sigma factor. AB - The periodontopathogen Porphyromonas gingivalis secretes potent pathogenic proteases, gingipains, via the type IX secretion system (T9SS). This system comprises at least 11 components; however, the regulatory mechanism of their expression has not yet been elucidated. Here, we found that the PorY (PGN_2001) PorX (PGN_1019)-SigP (PGN_0274) cascade is involved in the regulation of T9SS. Surface plasmon resonance (SPR) analysis revealed a direct interaction between a recombinant PorY (rPorY) and a recombinant PorX (rPorX). rPorY autophosphorylated and transferred a phosphoryl group to rPorX in the presence of Mn(2+). These results demonstrate that PorX and PorY act as a response regulator and a histidine kinase, respectively, of a two component system (TCS), although they are separately encoded on the chromosome. T9SS component-encoding genes were down regulated in a mutant deficient in a putative extracytoplasmic function (ECF) sigma factor, PGN_0274 (SigP), similar to the porX mutant. Electrophoretic gel shift assays showed that rSigP bound to the putative promoter regions of T9SS component-encoding genes. The SigP protein was lacking in the porX mutant. Co immunoprecipitation and SPR analysis revealed the direct interaction between SigP and PorX. Together, these results indicate that the PorXY TCS regulates T9SS mediated protein secretion via the SigP ECF sigma factor. PMID- 26996147 TI - A Solar Cell That Is Triggered by Sun and Rain. AB - All-weather solar cells are promising in solving the energy crisis. A flexible solar cell is presented that is triggered by combining an electron-enriched graphene electrode with a dye-sensitized solar cell. The new solar cell can be excited by incident light on sunny days and raindrops on rainy days, yielding an optimal solar-to-electric conversion efficiency of 6.53 % under AM 1.5 irradiation and current over microamps as well as a voltage of hundreds of microvolts by simulated raindrops. The formation of pi-electron|cation electrical double-layer pseudocapacitors at graphene/raindrop interface is contributable to current and voltage outputs at switchable charging-discharging process. The new concept can guide the design of advanced all-weather solar cells. PMID- 26996148 TI - Hypertrichotic Becker's nevi treated with combination 1,550 nm non-ablative fractional photothermolysis and laser hair removal. AB - BACKGROUND: The removal of Becker's nevi poses a significant challenge due to limited available therapeutic options and increased risk of adverse effects, including scarring and dyspigmentation. Herein, we present the use of the non ablative fractional photothermolysis in combination with laser hair removal for the treatment of hypertrichotic Becker's nevi. METHOD: Retrospective analysis of three patients with Becker's nevi revealed that two patients with hypertrichotic Becker's nevi had greater than 75% clearance with combination therapy, and one patient with atrichotic Becker's nevus had a similar result with monotherapy non ablative fractional photothermolysis. CONCLUSION: This report demonstrates the utility and safety of combination non-ablative fractional resurfacing and laser hair removal for the treatment of hypertrichotic Becker's nevi, and monotherapy non-ablative fractional photothermolysis for atrichotic Becker's nevi. Further comparative studies are necessary to determine optimal laser parameters, treatment schedules, and response duration. PMID- 26996150 TI - Response to correspondence to Hale et al. atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria. PMID- 26996149 TI - Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia. AB - Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs. PMID- 26996151 TI - Bio-based extraction and stabilization of anthocyanins. AB - This work reports a novel method of recovering anthocyanin compounds from highly pigmented grapes via a fermentation based approach. It was hypothesized that batch growth of Zymomonas mobilis on simple medium would produce both ethanol and enzymes/biomass-acting materials, the combination of which will provide a superior extraction when compared to simple alcohol extraction. To examine this hypothesis, Z. mobilis was fermented in a batch consisting of mashed Vitis vinifera and glucose, and the recovered anthocyanin pool was compared to that recovered via extraction with ethanol. Data indicated higher amounts of anthocyanins were recovered when compared to simple solvent addition. Additionally, the percent polymeric form of the anthocyanins could be manipulated by the level of aeration maintained in the fermentation. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:601-605, 2016. PMID- 26996152 TI - Cobalt allergy: suitable test concentration, and concomitant reactivity to nickel and chromium. AB - BACKGROUND: Cobalt allergy is frequent, but knowledge about exposure is limited. The patch test concentration and relevance of positive reactions are sometimes questioned. OBJECTIVES: To assess the suitability of cobalt 1% versus 0.5% for patch testing, and to analyse the co-occurrence of allergy to cobalt, chromium, and nickel. MATERIALS AND METHODS: Consecutive dermatitis patients (n = 656) were patch tested with cobalt chloride 0.5% and 1%, potassium dichromate 0.5%, and nickel sulfate 5%, all in petrolatum. Reactions were assessed on day (D)3, and on D6 or D7, and the reactivity and development of reactions were analysed. RESULTS: Allergy to any metal was shown in 31% of patients, allergy to cobalt in 14%, allergy to chromium in 7%, and allergy to nickel in 20%. A significant proportion (37%) of cobalt allergy cases were missed by cobalt 0.5% versus 1%, whereas the reactivity profiles were similar. Cobalt allergy was solitary, without concomitant allergy to chromium or nickel, in 50% of patients. CONCLUSIONS: Cobalt chloride 1% pet. is more suitable for patch testing than 0.5%. Solitary cobalt allergy is as frequent as concomitant allergy to cobalt and nickel or chromium. Sources of skin exposure to metals need to be identified for prevention of contact allergy. This is, owing to large knowledge gaps, particularly demanding for cobalt. PMID- 26996153 TI - Defining a breeding objective for Nile tilapia that takes into account the diversity of smallholder production systems. AB - In general, livestock and fish farming systems in developing countries tend to be highly diverse in terms of agro-ecological conditions and market orientation. There are no studies that have investigated if and how this diversity translates to varying preferences for breeding objective traits. This is particularly important for breeding programmes that are organized on a national level (e.g. government-supported nucleus breeding programmes). The aim of this study was to investigate whether Nile tilapia farmers with diverse production systems and economic constraints have different preferences for breeding objective traits. The second objective was to derive a consensus breeding goal, using weighted goal programming that could be used for a national breeding programme for Nile tilapia. A survey was conducted among 100 smallholder Nile tilapia farmers in Kenya to obtain preference values for traits of economic importance, by using multiple pairwise comparisons. Individual and group preference values were estimated using analytical hierarchy process. Low-income farmers preferred harvest weight, while medium- and high-income farmers preferred growth rate and survival. Grouping farmers according to market objective (fingerling production or fattening) showed that fingerling producers preferred growth rate and survival, while fattening farmers preferred harvest weight, height and thickness. Weighted goal programming was used to obtain consensus preference values, and these were used to derive desired gains for a breeding goal of a national breeding programme that takes into account the diversity of smallholder production systems. PMID- 26996154 TI - On the mechanism of high product selectivity for HCOOH using Pb in CO2 electroreduction. AB - While achieving high product selectivity is one of the major challenges of the CO2 electroreduction technology in general, Pb is one of the few examples with high selectivity that produces formic acid almost exclusively (versus H2, CO, or other byproducts). In this work, we study the mechanism of CO2 electroreduction reactions using Pb to understand the origin of high formic acid selectivity. In particular, we first assess the proton-assisted mechanism proposed in the literature using density functional calculations and find that it cannot fully explain the previous selectivity experiments for the Pb electrode. We then suggest an alternative proton-coupled-electron-transfer mechanism consistent with existing observations, and further validate a new mechanism by experimentally measuring and comparing the onset potentials for CO2 reduction vs. H2 production. We find that the origin of a high selectivity of the Pb catalyst for HCOOH production over CO and H2 lies in the strong O-affinitive and weak C-, H affinitive characteristics of Pb, leading to the involvement of the *OCHO species as a key intermediate to produce HCOOH exclusively and preventing unwanted H2 production at the same time. PMID- 26996155 TI - Multifunctional pDNA-Conjugated Polycationic Au Nanorod-Coated Fe3 O4 Hierarchical Nanocomposites for Trimodal Imaging and Combined Photothermal/Gene Therapy. AB - It is very desirable to design multifunctional nanocomposites for theranostic applications via flexible strategies. The synthesis of one new multifunctional polycationic Au nanorod (NR)-coated Fe3 O4 nanosphere (NS) hierarchical nanocomposite (Au@pDM/Fe3 O4 ) based on the ternary assemblies of negatively charged Fe3 O4 cores (Fe3 O4 -PDA), polycation-modified Au nanorods (Au NR-pDM), and polycations is proposed. For such nanocomposites, the combined near-infrared absorbance properties of Fe3 O4 -PDA and Au NR-pDM are applied to photoacoustic imaging and photothermal therapy. Besides, Fe3 O4 and Au NR components allow the nanocomposites to serve as MRI and CT contrast agents. The prepared positively charged Au@pDM/Fe3 O4 also can complex plasmid DNA into pDNA/Au@pDM/Fe3 O4 and efficiently mediated gene therapy. The multifunctional applications of pDNA/Au@pDM/Fe3 O4 nanocomposites in trimodal imaging and combined photothermal/gene therapy are demonstrated using a xenografted rat glioma nude mouse model. The present study demonstrates that the proper assembly of different inorganic nanoparticles and polycations is an effective strategy to construct new multifunctional theranostic systems. PMID- 26996157 TI - Metal nanoparticles triggered persistent negative photoconductivity in silk protein hydrogels. AB - Silk protein is a natural biopolymer with intriguing properties, which are attractive for next generation bio-integrated electronic and photonic devices. Here, we demonstrate the negative photoconductive response of Bombyx mori silk protein fibroin hydrogels, triggered by Au nanoparticles. The room temperature electrical conductivity of Au-silk hydrogels is found to be enhanced with the incorporation of Au nanoparticles over the control sample, due to the increased charge transporting networks within the hydrogel. Au-silk lateral photoconductor devices show a unique negative photoconductive response under an illumination of 325 nm, with excitation energy higher than the characteristic metal plasmon resonance band. The enhanced photoconductance yield in the hydrogels over the silk protein is attributed to the photo-oxidation of amino groups in the beta pleated sheets of the silk around the Au nanoparticles followed by the breaking of charge transport networks. The Au-silk nanocomposite does not show any photoresponse under visible illumination because of the localization of excited charges in Au nanoparticles. The negative photoconductive response of hybrid Au silk under UV illumination may pave the way towards the utilization of silk for future bio-photonic devices using metal nanoparticle platforms. PMID- 26996156 TI - Gestational weight gain, prepregnancy body mass index and offspring attention deficit hyperactivity disorder symptoms and behaviour at age 10. AB - OBJECTIVE: To assess offspring attention-deficit hyperactivity disorder (ADHD) symptoms and emotional/behavioural impairments at age 10 years in relation to maternal gestational weight gain (GWG) and prepregnancy body mass index (BMI). DESIGN AND SETTING: Longitudinal birth cohort from Magee-Womens Hospital, Pittsburgh, Pennsylvania (enrolled 1983-86). POPULATION: Mother-infant dyads (n = 511) were followed through pregnancy to 10 years. METHODS: Self-reported total GWG was converted to gestational-age-standardised z-scores. Multivariable linear and negative binomial regressions were used to estimate effects of GWG and BMI on outcomes. MAIN OUTCOME MEASURES: Child ADHD symptoms were assessed with the Conners' Continuous Performance Test. Child behaviour was assessed by parent and teacher ratings on the Child Behaviour Checklist (CBCL) and Teacher Report Form, respectively. RESULTS: The mean (SD) total GWG (kg) was 14.5 (5.9), and 10% of women had a pregravid BMI >=30 kg/m2 . Prepregnancy obesity (BMI of 30 kg/m2 ) was associated with increased offspring problem behaviours including internalising behaviours (adjusted beta 3.3 points, 95% CI 1.7-4.9), externalising behaviours (adjusted beta 2.9 points, 95% CI 1.4-4.6), and attention problems (adjusted beta 2.3 points, 95% CI 1.1-3.4) on the CBCL, compared with normal weight mothers (BMI of 22 kg/m2 ). There were nonsignificant trends towards increased offspring impulsivity with low GWG among lean mothers (adjusted incidence rate ratio 1.2, 95% CI 0.9-1.5) and high GWG among overweight mothers (adjusted incidence rate ratio 1.7, 95% CI 0.9-2.8), but additional outcomes did not differ by GWG z-score. Results were not meaningfully different after excluding high-substance users. CONCLUSIONS: In a low-income and high-risk sample, we observed a small increase in child behaviour problems among children of obese mothers, which could have an impact on child behaviour in the population. TWEETABLE ABSTRACT: Maternal obesity is associated with a small increase in child behaviour problems. PMID- 26996158 TI - Ubiquitin-like modifier FAT10 attenuates RIG-I mediated antiviral signaling by segregating activated RIG-I from its signaling platform. AB - RIG-I is a key cytosolic RNA sensor that mediates innate immune defense against RNA virus. Aberrant RIG-I activity leads to severe pathological states such as autosomal dominant multi-system disorder, inflammatory myophathies and dermatomyositis. Therefore, identification of regulators that ensure efficient defense without harmful immune-pathology is particularly critical to deal with RIG-I-associated diseases. Here, we presented the inflammatory inducible FAT10 as a novel negative regulator of RIG-I-mediated inflammatory response. In various cell lines, FAT10 protein is undetectable unless it is induced by pro inflammatory cytokines. FAT10 non-covalently associated with the 2CARD domain of RIG-I, and inhibited viral RNA-induced IRF3 and NF-kB activation through modulating the RIG-I protein solubility. We further demonstrated that FAT10 was recruited to RIG-I-TRIM25 to form an inhibitory complex where FAT10 was stabilized by E3 ligase TRIM25. As the result, FAT10 inhibited the antiviral stress granules formation contains RIG-I and sequestered the active RIG-I away from the mitochondria. Our study presented a novel mechanism to dampen RIG-I activity. Highly accumulated FAT10 is observed in various cancers with pro inflammatory environment, therefore, our finding which uncovered the suppressive effect of the accumulated FAT10 during virus-mediated inflammatory response may also provide molecular clue to understand the carcinogenesis related with infection and inflammation. PMID- 26996159 TI - Classification of Gemcitabine resistant Cholangiocarcinoma cell lines using synchrotron FTIR microspectroscopy. AB - Cholangiocarcinoma (CCA), a cancer of bile duct epithelium, is a major health problem in Thailand especially in the northeast. Overall treatment outcomes have not shown much improvement because the disease is usually detected at an advanced stage and often shows chemotherapeutic resistance. High-throughput Fourier Transform Infrared (FTIR) microspectroscopy can be used for cell classification and has the potential to diagnose cancer and possibly predict chemo-response. This study was aimed to differentiate gemcitabine-sensitive and gemcitabine resistant induction in two CCA cell lines (KKU-M139 and KKU-M214) and xenograft tissues using synchrotron-FTIR microspectroscopy. Partial Least Squares Discriminant Analysis (PLS-DA) could discriminate between chemo-sensitive and chemo-resistant cells in the FTIR fingerprint spectral region (1800-1000 cm-1 ) with more than 90% sensitivity and specificity. The chemo-resistant and chemo sensitive phenotypes were different in protein (amide I, amide II), lipids (carbonyl group and CH3 deformation) and phosphodiester from nucleic acids. Additionally, spectra from xenograft tissues showed similar results to the cell line study with marked differences between chemo-resistant and chemo-sensitive CCA tissues, and PLS-DA could discriminate the chemotherapeutic response with 98% sensitivity and specificity. This is the first study to demonstrate the use of FTIR microspectroscopy to assess chemo-response both in vitro and in vivo. PMID- 26996160 TI - Recent molecular and therapeutic advances in B-cell non-Hodgkin lymphoma in children. AB - Paediatric B-cell non-Hodgkin lymphoma (B-NHL) compromises a heterogeneous group of histological entities of which Burkitt lymphoma is the most common. In resource-rich countries, the expected cure rate is in excess of 85% with application of risk-adapted short intensive chemotherapy. In recent years, large paediatric cooperative group trials have sought to improve upon outcomes by decreasing the intensity of cytotoxic treatment as well as introducing targeted therapies, such as rituximab. These efforts have resulted in excellent outcomes, however there remains a group of high-risk patients for whom novel treatment approaches are needed. In this review, we will summarize the recent paediatric clinical trials in B-NHL as well as compare treatment approaches across the major cooperative groups. We will also highlight our current understanding of the molecular biology of paediatric B-NHL with a focus on how this may help guide future rational targeted therapy. PMID- 26996163 TI - NLRP3 Is Involved in Ischemia/Reperfusion Injury. AB - Inflammation plays a pivotal role in the ischemia/reperfusion (I/R) injury. Inflammatory response is initiated by the detection of pathogen-associated molecular patterns and/or damage-associated molecular patterns via extracellular and intracellular pattern recognition receptors. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing protein 3 (NLRP3) is a component of pattern recognition receptors and serves a vital role in inflammatory response by forming an intracellular multi-protein complex known as NLRP3 inflammasome. There is increasing evidence that NLRP3 inflammasome acts as guardians against host-derived danger materials. The inappropriate activation of NLRP3 contributes to the progression of I/R injury such as myocardial, cerebral, renal, hepatic and retinal I/R injuries. In this review, we summarize the role of NLRP3 in inflammatory response and discuss the relationship between NLRP3 and I/R injury. We also provide insights into new treatment strategies for targeting NLRP3 inflammasome, as well as the upstream and downstream components of NLRP3 in alleviating I/R injury. PMID- 26996161 TI - In vivo dynamics of active edema and lethal factors during anthrax. AB - Lethal and edema toxins are critical virulence factors of Bacillus anthracis. However, little is known about their in vivo dynamics of production during anthrax. In this study, we unraveled for the first time the in vivo kinetics of production of the toxin components EF (edema factor) and LF (lethal factor) during cutaneous infection with a wild-type toxinogenic encapsulated strain in immuno-competent mice. We stratified the asynchronous infection process into defined stages through bioluminescence imaging (BLI), while exploiting sensitive quantitative methods by measuring the enzymatic activity of LF and EF. LF was produced in high amounts, while EF amounts steadily increased during the infectious process. This led to high LF/EF ratios throughout the infection, with variations between 50 to a few thousands. In the bloodstream, the early detection of active LF and EF despite the absence of bacteria suggests that they may exert long distance effects. Infection with a strain deficient in the protective antigen toxin component enabled to address its role in the diffusion of LF and EF within the host. Our data provide a picture of the in vivo complexity of the infectious process. PMID- 26996162 TI - Anaesthetic management of acute airway obstruction. AB - The acutely obstructed airway is a medical emergency that can potentially result in serious morbidity and mortality. Apart from the latest advancements in anaesthetic techniques, equipment and drugs, publications relevant to our topic, including the United Kingdom's 4th National Audit Project on major airway complications in 2011 and the updated American Society of Anesthesiologists' difficult airway algorithm of 2013, have recently been published. The former contained many reports of adverse events associated with the management of acute airway obstruction. By analysing the data and concepts from these two publications, this review article provides an update on management techniques for the acutely obstructed airway. We discuss the principles and factors relevant to the decision-making process in formulating a logical management plan. PMID- 26996164 TI - Brain: The Potential Diagnostic and Therapeutic Target for Glaucoma. AB - Glaucoma is a form of multifactorial ocular neurodegeneration with immensely complex etiology, pathogenesis and pathology. Though the mainstream therapeutic management of glaucoma is lowering of intraocular pressure, there is, as of now, no cure for the disease. New evidences ardently suggest brain involvement in all aspects of this malady. This consequently advocates the opinion that brain should be the spotlight of glaucoma research and may form the impending and promising target for glaucoma diagnosis and treatment. The present analysis endeavors at understanding glaucoma vis-a-vis brain structural and/or functional derangement and central nervous system (CNS) degeneration. Commencing with the premise of developing some understanding about the brain-nature of ocular structures; we discuss the nature of the cellular and molecular moieties involved in glaucoma and Alzheimer's disease. Substantial deal of literature implies that glaucoma may well be a disease of the brain, nevertheless, manifesting as progressive loss of vision. If that is the case, then targeting brain will be far more imperative in glaucoma therapeutics than any other remedial regimen currently being endorsed. PMID- 26996165 TI - Neurobiology of Bipolar Disorder: Abnormalities on Cognitive and Cortical Functioning and Biomarker Levels. AB - Bipolar disorder (BD) affects 1 to 1.5% of the world population and consists of at least one manic episode (or hypomanic) associated with depressive episodes, interspersed with periods of euthymic mood. Recurrent crises lead to significant disability in BD patients, and correlates negatively to social and occupational adjustment. Such disability can be explained by a series of events, such as cortical and altered metabolic activity, impairments in cognitive functions, and in core anatomical structures involved in mood modulation. Therefore, our review aims to provide information on the current research related to the pathophysiology of BD. We will review the cognitive and brain functioning, and biomarkers of BD. The current literature shows that cognitive deficits are commonly observed in all phases in BD patients, independent of a remissive state. These deficits are assigned to functional, structural and metabolic changes, particularly in the pre-frontal cortex region, hippocampus and amygdala, along with the connections between them, as well as decreased baseline brain-derived neurotrophic factor levels or imbalance between pro- and anti-inflammatory cytokines, implying a lower physical ability to reestablish from a stressful stimulus. BD patients effectively present a differentiated pattern of cortical, neuroanatomical and functional responses. It is suggested that physiological processes occur differently in bipolar subjects compared to healthy individuals, affecting behavior and brain function in such patients. Future directions are yet necessary to establish the best way to neutralize or reverse these events. PMID- 26996166 TI - Synthesis of Novel 8-alkylamino-5, 6-dihydro-4H-benzo[f] [1,2,4]triazolo [4,3 a]azepines as Anticonvulsant Agents. AB - A series of new 8-alkylamino-5, 6-dihydro-4H-benzo[f][1,2,4]triazolo [4,3 a]azepine derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, subcutaneous pentylenetetrazol (scPTZ) test, and their neurotoxicity was evaluated by the rotarod neurotoxicity test. The results of these tests showed that 8-heptylamino-5,6- dihydro-4H benzo[f][1,2,4] triazolo[4,3-a]azepine (7g) was the most promising compound, with median effective dose (ED50) of 19.0 mg/kg, and protective index (PI) value of 14.8 in the MES test, which is much higher than the PI value of the prototype antiepileptic drug carbamazepine (PI = 8.1), phenytoin (PI = 6.9), phenobarbital (PI = 3.2), and sodium valproate (PI = 1.6). The possible structure-activity relationship was discussed. PMID- 26996167 TI - Vertical and Horizontal Convergences of Targeting Pathways in Combination Therapy with Baicalin and Jasminoidin for Cerebral Ischemia. AB - Baicalin (BA) and jasminoidin (JA) exert an additive effect in the treatment of cerebral ischemia, but the underlying molecular mechanism is still unclear. One hundred mice with focal cerebral ischemia/re-perfusion injury were divided into 5 groups: BA, JA, combination therapy (BJ), sham and vehicle. The differentially expressed genes identified by microarray consisting of 374 cDNAs were uploaded into GeneGo MetaCore software for pathway analyses. Networks were constructed to visualize the interactions of the differentially expressed genes. Among the top ten pathways and processes, we found 5, 3, 2 overlapping pathways and 6, 4, 6 overlapping processes between the BA and JA, BA and BJ, JA and BJ groups, respectively; of which 1 pathway and 3 processes were shared by all the three groups. Six representative pathways and 3 processes were activated only in BJ, such as Gamma-secretase proteolytic targets,etc. These BJ representative targeting pathways showed both vertical (e.g. Cytoplasmic/mitochondrial transport of proapoptotic Bid Bmf and Bim) and horizontal (e.g. Endothelin-1/EDNRA signaling) convergences with those of the BA and JA groups based on the upstream and downstream relationship of cerebral ischemia network, which may help to reveal their additive mechanism in the treatment of cerebral ischemia. Network comparison identified important transcription factors that regulated some of the other BJ related genes, such as cMyb and NF-AT. Such a systemic approach based on multiple pathways and networks may provide a robust path to understand the complex pharmacological variations of combination therapies. PMID- 26996168 TI - Preliminary Pharmacological Screening of Some Thiosemicarbazide, s-triazole, and Thiadiazole Derivatives. AB - Two thiosemicarbazide derivatives 1 and 2, three 2-amino-1,3,4-thiadiazole derivatives 3-5, and three N1- substituted-4-methyl-1,2,4-triazole-5-thione derivatives 6-8 were synthesized and evaluated for their central nervous system effects using rodent behavioral models. With the exception of 6, all compounds were devoid of neurotoxicity and they did not affect the body temperature of mice. New lead structures 1-4 with potential analgesic activity were identified. PMID- 26996169 TI - In Silico Analysis of Green Tea Polyphenols as Inhibitors of AChE and BChE Enzymes in Alzheimer's Disease Treatment. AB - Alzheimer's disease (AD) is the most frequent cause of dementia, especially in the elderly. AD is the most common progressive neurodegenerative disorder, which involves the loss of structure and function of cholinergic neurons. Moreover, if these neuronal changes cannot be compensated, this may ultimately lead to neurodegenerative processes. Therefore, most of the drug therapies are based on the cholinergic hypothesis, which suggests that AD begins as a deficiency in the production of the neurotransmitter acetylcholine. In this context, many inhibitors play an important role in AD treatment among which acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have more potential in the treatment process of AD. In this study, we selected tea polyphenols of green tea which are reported as AChE and BChE inhibitors used in the treatment of AD. The molecular docking results revealed that polyphenols exhibit interactions and inhibit by binding with AChE and BChE. The amount of energy to bind with AChE and BChE needed by Epigallocatechin-3-gallate was lowest at about -14.45 and 13.30 kcal/mol, respectively. All compounds showed binding energy values ranging between -14.45 to -9.75 kcal/mol for both types of enzymes. The present docking study suggests that tea polyphenols inhibit AChE as well as BChE and enhance the cholinergic neurotransmission by prolonging the time. However, AChE molecules remain in the synaptic cleft. In consideration to these findings, cholinesterase inhibitors are suggested as the standard drugs for the treatment of AD. PMID- 26996170 TI - Decreased Expression of Sox-1 in Cerebellum of Rat with Generalized Seizures Induced by Kindling Model. AB - The single feature of all malformations in cortical development is the clinical association with epilepsy. It has been proven that Sox-1 expression is essential during neurodevelopment and it is reported that Sox-1 knockout mice present spontaneous generalized seizures. Particularly in cerebellum, Sox-1 plays a key role in the Bergmann's glia (BG) function, which allows the correct function of the Purkinje cells (PC). The targets of PC are the dentate and interpositus nuclei, which form the main cerebellar efferents involved in the physiopathology of epilepsy. Here we present the Sox-1 expression in cerebellum of rats during electric amygdala-kindling. We obtained seizures and once they had 3, 15 and 45 electric stimuli, the animals were sacrificed; the cerebellum was processed for inmunohistochemistry and Western blot analysis was performed to determine Sox-1 expression. Liquid chromatography was performed to examine gammaaminobutyric acid (GABA) and glutamate concentration. According to the literature, a progressive increase was observed in the electrographic and behavioral parameters. We found that Sox-1 expression in 15 and 45-stimuli groups had a statistically significant decrease as compared with controls, while the 3-stimuli group was similar to the control group. The concentration of glutamate was increased in rats with 45 stimuli. We can conclude that Sox-1 expression decreases as the number of seizures increases, and this is probably due to an altered glutamate regulation by a dysfunctional BG. In this way, we can suggest this mechanism as a one possible explanation of how the cerebellum participates in the pathophysiology of epilepsy. PMID- 26996171 TI - Establishment of Cell-Based Neuroglobin Promoter Reporter Assay for Neuroprotective Compounds Screening. AB - Neuroglobin (Ngb) has been demonstrated to be neuroprotective against stroke and neurodegenerative diseases, thus upregulating Ngb might be a novel approach for neuroprotection. In this study we aimed to establish cell-based Ngb reporter systems for screening neuroprotective compounds targeting Ngb upregulation. We developed both mouse and human stable Ngb reporter systems containing a luciferase reporter gene directed by mouse and human Ngb promoter, respectively. To validate these reporter systems, we used them to screen a pool of natural plant compounds. RT-PCR was used to verify the Ngb-upregulating effects of selected compounds, and neurotoxicity assay was used to test their neuroprotection effects in primary cultured neurons. We identified polydatin, genistein, daidzein, biochanin A and formononetin that can upregulate both mouse and human Ngb promoter activity. RT-PCR confirmed that polydatin, genistein and formononetin significantly increased Ngb mRNA expression in primary neurons. Furthermore, formononetin significantly decreased oxygen-glucose deprivation (OGD)-induced neurotoxicity. Moreover, inhibition of cAMP response element binding protein (CREB) showed that CREB is required for formononetin-induced Ngb upregulation. These results suggest that these Ngb reporter systems are suitable for neuroprotective compound screening, which will be used to screen larger compound libraries for more potent neuroprotectants. This preliminary study will facilitate the development of Ngb-targeted therapeutics for stroke and neurodegenerative diseases. PMID- 26996172 TI - Neuroinflammation and Immunity: A New Pharmacological Target in Depression. AB - Major depressive disorder (MDD) is a debilitating illness that affects a significant percentage of the world population. This disorder is associated with diminished productivity and reduced quality of life; unfortunately the underlying pathophysiological mechanisms are not fully clarified. Recently, several studies have suggested that psychiatric disorders could be considered as inflammatory disorders; nevertheless. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors There is strong evidence that depression involves alterations in multiple aspects of immunity that may contribute to the development or exacerbation of a number of medical disorders and also may play a role in the pathophysiology of depressive symptoms. This review highlights the role of neuroinflammation and immunity in the pathophysiology of psychiatric disorders such as MDD. PMID- 26996173 TI - Global Expression Studies of Schizophrenic Brain: A Meta-Analysis Study Linking Neurological Immune System with Psychological Disorders. AB - Schizophrenia, a psychological disorder with enormous societal impact, is a result of abnormalities in gene expression and dysregulation of the immune response in the brain. Few studies have been conducted to understand its etiology, however, the exact molecular mechanism largely remains unknown, though some poorly understood theories abound. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis. We retrieved genome-wide mRNA expression data and clinico-pathological information from five independent studies of schizophrenic patients from Gene Expression Omnibus database. We continued further with three studies having common platform. Our result showed a total of 527 differentially expressed genes of which 314 are up regulated and 213 are down regulated. After adjusting the sources of variation, we carried out pathway and gene ontology analysis, and observed alteration of 14-3-3-mediated signaling, gamma-aminobutyric acid receptor signaling, role of nuclear factor of activated T-cells in regulation of the immune response, G beta gamma signaling, dopamine- and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 feedback in cAMP signaling, complement system, axonal guidance signaling, dendritic cell maturation, cAMP response element-binding protein signaling in neurons and interleukin-1 signaling pathways and networks. Conclusively, our global gene expression pathway and gene set enrichment analysis studies suggest disruption of many common pathways and processes, which links schizophrenia to immune and central nervous system. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis. PMID- 26996174 TI - Neuro-Inflammatory Mechanisms in Developmental Disorders Associated with Intellectual Disability and Autism Spectrum Disorder: A Neuro- Immune Perspective. AB - Intellectual disability (ID) and autism are present in several neurodevelopmental disorders and are often associated in genetic syndromes, such as Fragile X and Rett syndromes. While most evidence indicates that a genetic component plays an important role in the aetiology of both autism and ID, a number of studies suggest that immunological dysfunctions may participate in the pathophysiology of these disorders. Brain-specific autoantibodies have been detected in the sera of many autistic children and autoimmune disorders are increased in families of children with autism. Furthermore, cytokine imbalance has been reported in children with autism. These results may reflect an inappropriate immune response to environmental factors, such as infectious or toxic exposure. The role of microglia as sensors of pre- and post-natal environmental stimuli and its involvement in the regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis has recently emerged. An abnormal immune response during critical windows of development and consequent abnormal production of neuro-inflammatory mediators may have an impact on the function and structure of brain and can play a role in the pathogenesis of non syndromic autism. Recent evidence suggests an involvement of neuro-inflammation also in syndromic forms of autism and ID. Immune dysregulation has been found in children with Fragile X syndrome and an intrinsic microglia dysfunction has been recently reported in Rett syndrome. The present review summarizes the current literature suggesting that neuro-inflammatory mechanisms may contribute to the pathogenesis of different ID- and autism-associated disorders, thus representing common pathophysiological pathways and potential therapeutic targets. PMID- 26996175 TI - A Link Between Nerve Growth Factor Metabolic Deregulation and Amyloid-beta-Driven Inflammation in Down Syndrome. AB - In Alzheimer's disease and Down syndrome, cholinergic neurons of the basal forebrain progressively degenerate. This neurotransmitter system is the main source of acetylcholine to the cortex and hippocampus. In the mature and fully differentiated central nervous system, the phenotype of forebrain cholinergic neurons and their nerve terminals in cortex and hippocampus depend on the continuous endogenous supply of nerve growth factor (NGF). It has been recently demonstrated that NGF is secreted from cortical neurons in an activity-dependent manner as a precursor molecule, proNGF. Individuals with Alzheimer's disease and Down syndrome exhibit proNGF accumulation in cortex, yet cholinergic neurons become atrophic in both diseases, despite the apparent abundance of the NGF precursor. This review illustrates the recent evidence that NGF metabolism is affected both in Alzheimer's disease and in Down syndrome brains and also discusses a role for amyloid-beta peptides and central nervous system inflammation in unleashing such deficits. It further considers the potential of the NGF metabolic pathway as a new pharmacological target to slow down the neurodegenerative process both in Alzheimer's disease and in individuals with Down syndrome. PMID- 26996176 TI - Disease-Induced Neuroinflammation and Depression. AB - Progression of major depression, a multifactorial disorder with a neuroinflammatory signature, seems to be associated with the disruption of body allostasis. High rates of comorbidity between depression and specific medical disorders, such as, stroke, chronic pain conditions, diabetes mellitus, and human immunodeficiency virus (HIV) infection, have been extensively reported. In this review, we discuss how these medical disorders may predispose an individual to develop depression by examining the impact of these disorders on some hallmarks of neuroinflammation known to be impaired in depressed patients: altered permeability of the blood brain barrier, immune cells infiltration, activated microglia, increased cytokines production, and the role of inflammasomes. In all four pathologies, blood brain barrier integrity was altered, allowing the infiltration of peripheral factors, known to activate resident microglia. Evidence indicated morphological changes in the glial population, increased levels of circulating pro-inflammatory cytokines or increased production of these mediators within the brain, all fundamental in neuroinflammation, for the four medical disorders considered. Moreover, activity of the kynurenine pathway appeared to be enhanced. With respect to the inflammasome NLRP3, a new target whose role in neuroinflammation is emerging as being important, accumulating data suggest its involvement in the pathogenesis of brain injury following stroke, chronic pain conditions, diabetes mellitus or in HIV associated immune impairment. Finally, data gathered over the last 10 years, indicate and confirm that depression, stroke, chronic pain, diabetes, and HIV infection share a combination of underlying molecular, cellular and network mechanisms leading to a general increase in the neuroinflammatory burden for the individual. PMID- 26996177 TI - Endoplasmic Reticulum Stress and Bipolar Disorder - Almost Forgotten Therapeutic Drug Targets in the Unfolded Protein Response Pathway Revisited. AB - Bipolar Disorder (BD) is characterized by recurring mood swings, which are not completely understood yet. So far, it is an accepted theory that multiple factors contribute to pathogenesis of BD according to the vulnerability-stressmodel. This model combines on the one hand biological predisposing vulnerability, and on the other hand several chronic and acute stressful negative events as underlying mechanisms of BD. Recently, ER (Endoplasmic Reticulum) stress reached the spotlight of BD research again. The expression of the chaperone BiP (syn. GRP78/glucose-regulated protein, 78kDa), which is highly expressed in the Endoplasmic Reticulum (ER), is upregulated by different kinds of mood stabilizers. These results implied that the ER, an organelle which is prone towards different kinds of cellular stress, might be involved in the pathophysiology of BD. This hypothesis was further strengthened by hypothesis driven genetic association studies, which showed significant association of BiP promotor polymorphisms with BD. Also other ER-stress associated genes like XBP1 (X-box binding protein 1) or GRP94 (glucose-regulated protein, 94kDa, synonym for heat shock protein HSP90B1) were recently linked to BD in hypothesis driven gene association studies. In addition to the proteins mentioned before, our review focuses on further UPR (Unfolded Protein Response) related proteins associated with BD and raises the hypothesis that ER-stress may represent a common interface between BD and obesity which is overrepresented in BD patients. Finally, members of the UPR pathway are discussed as putative targets for mood stabilizers. PMID- 26996178 TI - Alzheimer's Disease and Autistic Spectrum Disorder: Is there any Association? AB - Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders respectively, with devastating effects not only on the individual but also the society. Collectively, a number of factors contribute to the expression of ASD and AD. It is of utmost curiosity that these disorders express at different stages of life and there is an involvement of certain susceptible genes. This genetic basis makes the background of common associations like memory deficits, cognition changes, demyelination, oxidative stress and inflammation, an integral part of both disorders. Modern technology resulting in genetically modified crops and increase in gadgets emitting electromagnetic frequencies have resulted in enhanced risks for neurological dysfunctions and disorders like ASD and AD. Subsequent advances in the psychological, pharmacological, biochemical and nutritional aspects of the disorders have resulted in the development of newer therapeutic approaches. The common clinical features like language impairment, executive functions, and motor problems have been discussed along with the patho-physiological changes, role of DNA methylation, myelin development, and heavy metals in the expression of these disorders. Psychopharmacological and nutritional approaches towards the reduction and management of risk factors have gained attention from the researchers in recent years. Current major therapies either target the inflammatory pathways or reduce cellular oxidative stress. This contribution focuses on the commonalities of the two disorders. PMID- 26996179 TI - Mood Stabilizers, Oxidative Stress and Antioxidative Defense in Euthymia of Bipolar Disorder. AB - BACKGROUND: Hitherto literature indicates that mood stabilizers exert variable effects on oxidative and antioxidative systems, which are involved in the pathogenesis of Bipolar Disorder. Herein we primarily sought to characterize markers of peripheral oxidative stress during euthymia in adults with Bipolar Disorder under current intake of different mood stabilizers (lithium, anticonvulsants and atypical antipsychotics/AAPs). METHODS: Peripheral oxidative stress parameters (TBARS/Thiobarbituric acid-reactive-substances, MDA/ malondialdehyde and carbonyl proteins) and antioxidative markers (SOD/Cu/Zn superoxide dismutase, GST/glutathione Stransferase and TAC/total antioxidative capacity) were measured in serum of 115 euthymic bipolar individuals (50 females, 65 males; HAMD<11 and YMRS<8). Differences in (anti)oxidative markers between bipolar participants treated with different mood stabilizing medication were tested with MANCOVAS and ANCOVAS with SPSS.21. RESULTS: Bipolar individuals taking lithium had significantly lower oxidative parameters than test persons without lithium (multivariate effect for MDA and TBARS: F(2/182)= 3.956, p= 0.021; univariate effect for MDA: F(2/182)= 7.880, p= 0.006, Partial eta2= 0.041). Subjects with AAPs had significantly higher MDA and TBARS levels compared to participants without AAPs (multivariate effect F(2/182)= 3.122, p= 0.046, Partial eta2= 0.033). Patients taking anticonvulsants had significantly lower GST levels than patients without antiepileptic medication (F(1/165)= 4.501, p= 0.035, Partial eta2= 0.027). CONCLUSION: Lithium taking participants had the lowest MDA and TBARS levels, while AAP taking test persons had high oxidative stress markers. The observed effects on oxidative markers may provide a mechanistic basis for understanding lithium's neuroprotective effects. PMID- 26996180 TI - [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Indications for Treatment]. AB - The landscape of treatment for HCV infection has evolved substantially with the advent of highly effective direct-acting antiviral agents (DAA). The Korean Association for the Study of the Liver updated guideline for managemnt of hepatitis C in accordance with the introduction of DAA into practice in late 2015. Due to high effectiveness and few side effects of DAA, indications for treatment has been widened to include patients who had been contraindicated for the combination treatment of peginterferon-alpha and ribavirin, i.e. decompensated cirrhosis and pre- and post-liver transplant setting. As succeesul treatment of HCV can reduce complications of cirrhosis, development of hepatocelluar carcinoma and liver-related mortality, and improve extrahepatic manifestions, all HCV-infected patients with no contraindication should be considered for treatment. Considering the risk for morbidity and mortality and benefit of treatment, patients with advanced fibrosis >=F3 including compensated and decompensated cirrhosis, those in the pre- and post-tranplasnt setting, and those with severe extrahepatic manifestations including HCV-related mixed cryoglobulinemia and glomerulonephritis should be given priority for treatment. PMID- 26996181 TI - [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Chronic Hepatitis C Genotype 1]. AB - The introduction of direct-acting antiviral agents (DAAs) has markedly improved the sustained virological response (SVR) rates in patients with chronic hepatitis C. Currently, four classes of DAAs targeting three HCV proteins (NS3, NS5A, and NS5B) have been approved for treatment in many countries. Since drugs show advantages and disadvantages, use of a combination of two or more DAAs with different targets or addition of ribavirin in a difficult-to-treat patient shows an SVR rate of ~90% after 12 weeks of treatment or expanded treatment for 24 weeks. Various types of DAA are awaiting approval which will improve the treatment of chronic hepatitis C virus genotype 1 infection. However, high costs, drug resistance and interactions between various drugs remain to be overcome. With further advances in the development of antiviral agents, it could be expected that in the near future, there will be DAAs that are affordable and cost effective, require shorter treatment duration, effective in a broad range of patients, and have less side effects and drug-drug interactions. PMID- 26996183 TI - [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Patients with Decompensated Cirrhosis]. AB - HCV-related decompensated liver cirrhosis is a life-threatening illness with an average 5-year survival rate of 50%. Because these patients have higher risk of morbidity and mortality including development of hepatocellular carcinoma, the benefits of eradicating the virus may be greater than in those with less-advanced disease. Recently, direct-acting antiviral agents (DAAs) are replacing interferon based regimens that have serious adverse events and low tolerability in the treatment of HCV infection. Many clinical trials using combination of several DAAs with or without ribavirin are now actively on-going in HCV-related decompensated cirrhosis, and encouraging data are beginning to appear. In this review, recent advances in the treatment of HCV-related decompensated cirrhosis are introduced with special focus on new DAAs. PMID- 26996182 TI - [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Chronic Hepatitis C Genotype 2 and 3]. AB - Ever since direct-acting antiviral agents (DAA) have been approved and released into the world, numerous studies on the efficacy, adverse effects and drug-drug interactions of interferon-free DAA combination therapy have been studied and published. With all oral DAA therapy showing sustained virological response rate of 80-90% with minimal adverse events, HCV eradication has now become a realistic goal. DAA combination treatments were approved and adapted to practice in Korea in 2015, and Korean Association for the Study of the Liver (KASL) has revised the guideline based on the systematic approach that reflects evidence-based medicine and expert opinions. In this article, new recommendations for treatment of chronic HCV genotype 2 and 3 infected patients will be introduced base on KASL practice guidelines for management of hepatitis C that has been updated in 2015. PMID- 26996185 TI - [Successful Management of Periampullary Diverticular Bleeding with Hemoclipping Using Side-viewing Endoscope during Endoscopic Retrograde Cholangiopancreatography]. AB - Periampullary diverticulum is commonly found during endoscopy and can occur at any age although its prevalence increases with age. Periampullary diverticular bleeding is a rare and difficult to diagnose during clinical practice because of its unique appearance and location. This often can lead to massive bleeding and interfere with adequate bleeding control. Endoscopic management on duodenal diverticular bleeding is limited compared to colonic diverticular bleeding due to lack of experience. Herein, we report a case of active bleeding from a periampullary diverticulum during bile duct stone extraction diagnosed by side viewing endoscope and successfully controlled using hemoclips without any complications. PMID- 26996184 TI - Perigastric Abscess as a Complication of Endoscopic Submucosal Dissection for Early Gastric Cancer: First Case Report. AB - Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a widely accepted and well established procedure because of its curative potential and low invasiveness compared with surgery. Perforation is a potential major complication during ESD, and non-surgical treatments such as endoscopic closure with clips are sufficient in most cases. Here, we report a case of perigastric abscess that occurred as a complication of ESD for EGC. The patient improved with administration of antibiotics without surgical intervention. PMID- 26996186 TI - Common Bile Duct Obstruction Due to a Large Stone at the Duodenal Stump. AB - Enterolith is a rare complication of Billroth II gastrectomy. Most enterolith cases have been reported in association with diverticula, tuberculosis, and Crohn's disease. We report the case of a huge enterolith that developed in the duodenal stump following common bile duct obstruction and cholangitis, necessitating surgery. The enterolith was clearly visible on the abdominal computed tomography. It was removed through a duodenotomy. The surgery was successful without any significant complications. PMID- 26996187 TI - Pseudomyxoma Peritonei in a Patient with History of Breast Cancer. AB - Pseudomyxoma peritonei is a very rare condition, and even rarer in patients with history of cancer. A 70-year old woman with a history of breast cancer was admitted with abdominal pain and distention. Abdominal computed tomography revealed ascites collection, diffuse engorgement and infiltration of the mesenteric vessel, suggesting peritonitis or peritoneal carcinomatosis. Diagnostic paracentesis was attempted several times, but a sufficient specimen could not be collected due to the thick and gelatinous nature of the ascites. Therefore, the patient underwent diagnostic laparoscopy for tissue biopsy of the peritoneum, which indicated pseudomyxoma peritonei. However, the origin of the pseudomyxoma peritonei could not be identified intraoperatively due to adhesions and large amount of mucoceles. Systemic chemotherapy was performed using Fluorouracil, producing some symptomatic relief. After discharge, abdominal pain and distention gradually worsened, so at 18 months after initial diagnosis the patient received palliative surgery based on massive mucinous ascites and palpable mass at the omentum. The patient expired after surgery due to massive bleeding. PMID- 26996192 TI - Data mining spontaneous adverse drug event reports for safety signals in Singapore - a comparison of three different disproportionality measures. AB - OBJECTIVES: Quantitative data mining methods can be used to identify potential signals of unexpected relationships between drug and adverse event (AE). This study aims to compare and explore the use of three data mining methods in our small spontaneous AE database. METHODS: We consider reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Gamma Poisson Shrinker (GPS) assuming two different sets of criteria: (1) ROR-1.96SE>1, IC-1.96SD>0, EB05>1 (2) ROR-1.96SE>2, IC-1.96SD>1, EB05 >2. Count of drug-AE pairs >=3 was considered for ROR and GPS. RESULTS: The Health Sciences Authority, Singapore received 151,180 AE reports between 1993 and 2013. ROR, BCPNN and GPS identified 2,835, 2,311 and 2,374 significant drug-AE pairs using Criterion 1, and 1,899, 1,101 and 1,358 respectively using Criterion 2. The performance of the three methods with respect to specificity, positive predictive value and negative predictive value were similar, although ROR yielded a higher sensitivity and larger area under the receiver operating characteristic curve. ROR and GPS picked up some potential signals which BCPNN missed. CONCLUSIONS: The defined threshold used for ROR (Criterion 1) is a useful screening tool for our small database. It may be used in conjunction with GPS to avoid missed signals. PMID- 26996193 TI - Histamine and Histaminergic Receptors in Colorectal Cancer: From Basic Science to Evidence-based Medicine. AB - BACKGROUND: Histamine is an imidazolic compound performing a crucial function in the pathogenesis of inflammation. Several studies have also emphasized its pro carcinogenic effect in colorectal cancer (CRC). OBJECT: In fact, increased histamine levels have been observed in CRC and a decreased catabolism of this molecule is typical of colorectal adenomas. Additional data have demonstrated that CRC is characterized by an altered balance of histamine receptors (HRs); in fact, HR1 and HR4 are down-regulated in CRC, while HR2 is overexpressed. METHOD: Based on this evidence, we reviewed several studies investigating the role of HR2 antagonists (HR2A), such as cimetidine in CRC. RESULTS: From a clinical point of view, HR2A may prolong the survival rates of patients with CRC, and a recent meta analysis seems to confirm this finding. From a biological perspective, it has been demonstrated that HR2A could have a beneficial effect on CRC for many reasons: i) promotion of peri-tumoral lymphocyte growth and improvement of immune response against the tumor, ii) suppression of adhesion molecules which might favor metastasis, iii) anti-angiogenetic activity (reduction of VEGF), iv) increased production of some cytokines which may counteract tumor growth, such as tumor necrosis factor (TNF) alpha, interleukin (IL)-10 and IL-15. On the contrary, HR1 antagonists did not demonstrate any beneficial effect on CRC. Therefore, it is presumable that histamine could be a relevant player in the development of CRC, but its effect might be mediated by an imperfect homeostasis of its receptors. CONCLUSION: In this scenario, HR2A could inhibit carcinogenesis whereas HR2 might act as a pro-carcinogenetic, while HR1 and HR4, being suppressed in CRC, may antagonize neoplastic development. PMID- 26996194 TI - Synthesis and Characterization of AICAR and DOX Conjugated Multifunctional Nanoparticles as a Platform for Synergistic Inhibition of Cancer Cell Growth. AB - The success of cancer treatment depends on the response to chemotherapeutic agents. However, malignancies often acquire resistance to drugs if they are used frequently. Combination therapy involving both a chemotherapeutic agent and molecularly targeted therapy may have the ability to retain and enhance therapeutic efficacy. Here, we addressed this issue by examining the efficacy of a novel therapeutic strategy that combines AICAR and DOX within a multifunctional platform. In this context, we reported the bottom-up synthesis of Fe3O4@SiO2(FITC)-FA/AICAR/DOX multifunctional nanoparticles aiming to neutralize survivin (BIRC5) to potentiate the efficacy of DOX against chemoresistance. The structure of nanoparticles was characterized by dynamic light scattering (DLS), zeta-potential measurement, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and electron microscopy (SEM and STEM with EDX) techniques. Cellular uptake and cytotoxicity experiments demonstrated preferentially targeted delivery of nanoparticles and an efficient reduction of cancer cell viability in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat, and MIA PaCa-2). These results indicate that the multifunctional nanoparticle system possesses high inhibitory drug association and sustained cytotoxic effect with good biocompatibility. This novel approach which combines AICAR and DOX within a single platform might be promising as an antitumor treatment for cancer. PMID- 26996188 TI - Differentiation of murine models of "negative ERG" by single and repetitive light stimuli. AB - PURPOSE: Marked attenuation of the single-flash electroretinographic (ERG) b-wave in the presence of a normal-amplitude or less-attenuated a-wave is commonly referred to as the "negative ERG." The purpose of this study was to investigate whether the disparate origins of the negative ERG in three murine models can be discriminated using flickering stimuli. METHODS: Three models were selected: (1) the Nyx (nob) mouse model of complete congenital stationary night blindness, (2) the oxygen-induced retinopathy (OIR) rat model of retinopathy of prematurity (ROP), and (3) the Rs1 knockout (KO) mouse model of X-linked juvenile retinoschisis. Directly after a dark-adapted, single-flash ERG luminance series, a flicker ERG frequency series (0.5-30 Hz) was performed at a fixed luminance of 0.5 log cd s/m(2). This series includes frequency ranges that are dominated by activity in (A) the rod pathways (below 5 Hz), (B) the cone ON-pathway (5-15 Hz), and (C) the cone OFF-pathway (above 15 Hz). RESULTS: All three models produced markedly attenuated single-flash ERG b-waves. In the Nyx (nob) mouse, which features postsynaptic deficits in the ON-pathways, the a-wave was normal and flicker responses were attenuated in ranges A and B, but not C. The ROP rat is characterized by inner-retinal ischemia which putatively affects both ON- and OFF bipolar cell activity; flicker responses were reduced in all ranges (A-C). Notably, the choroid supplies the photoreceptors and is thought to be relatively intact in OIR, an idea supported by the nearly normal a-wave. Finally, in the Rs1 KO mouse, which has documented abnormality of the photoreceptor-bipolar synapse affecting both ON- and OFF-pathways, the flicker responses were attenuated in all ranges (A-C). The a-wave was also attenuated, likely as a consequence to schisms in the photoreceptor layer. CONCLUSION: Consideration of both single-flash and flickering ERG responses can discriminate the functional pathology of the negative ERG in these animal models of human disease. PMID- 26996195 TI - The Dark-Purple Tea Cultivar 'Ziyan' Accumulates a Large Amount of Delphinidin Related Anthocyanins. AB - Recently, we developed a novel tea cultivar 'Ziyan' with distinct purple leaves. There was a significant correlation between leaf color and anthocyanin pigment content in the leaves. A distinct allocation of metabolic flow for B-ring trihydroxylated anthocyanins and catechins in 'Ziyan' was observed. Delphinidin, cyanidin, and pelargonidin (88.15 mg/100 g FW in total) but no other anthocyanin pigments were detected in 'Ziyan', and delphinidin (70.76 mg/100 g FW) was particularly predominant. An analysis of the catechin content in 'Ziyan' and eight other cultivars indicated that 'Ziyan' exhibits a preference for synthesizing B-ring trihydroxylated catechins (with a proportion of 74%). The full-length cDNA sequences of flavonoid pathway genes were isolated by RNA-Seq coupled with conventional TA cloning, and their expression patterns were characterized. Purple-leaved cultivars had lower amounts of total catechins, polyphenols, and water extract than ordinary non-anthocyanin cultivars but similar levels of caffeine. Because dark-purple-leaved Camellia species are rare in nature, this study provides new insights into the interplay between the accumulations of anthocyanins and other bioactive components in tea leaves. PMID- 26996196 TI - Neural correlates of improved executive function following erythropoietin treatment in mood disorders. AB - BACKGROUND: Cognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance. METHOD: Patients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task. RESULTS: EPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28-0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ?0.08). CONCLUSIONS: The present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT00916552. PMID- 26996197 TI - Changes in whole-blood PUFA and their predictors during recovery from severe acute malnutrition. AB - Children with severe acute malnutrition (SAM) with complications require in patient management including therapeutic feeding. Little attention has been given to the effects of these feeds on the essential fatty acid status of children with SAM. The objective of this study was to describe changes in the PUFA composition in whole blood in children with SAM during treatment and to determine predictors of change. This prospective study took place in a paediatric nutrition rehabilitation unit in Kampala, Uganda, and assessed whole-blood fatty acid composition of children with SAM at admission, transition, discharge and follow up (8 and 16 weeks). ANCOVA was used to identify predictors of change in whole blood PUFA. The study included 120 children with SAM and twenty-nine healthy control children of similar age and sex. Among the SAM children, 38 % were female and 64 % had oedema. Whole-blood n-6 PUFA proportions increased from admission to follow-up, except for arachidonic acid, which decreased by 0.79 (95 % CI 0.46, 1.12) fatty acid percentage (FA%) from admission to transition and 0.10 (95 % CI 0.23, 0.44) FA% at discharge. n-3 Long-chain (LC) PUFA decreased by 0.21 (95 % CI 0.03, 0.40) FA% at discharge and 0.22 (95 % CI 0.01, 0.42) FA% at 8 weeks of follow-up. This decrease was greater in children from families with recent fish intake and those with nasogastric tube feeding. Current therapeutic feeds do not correct whole-blood levels of LCPUFA, particularly n-3 LCPUFA, in children with SAM. Increased attention is needed to the contents of n-3 LCPUFA in therapeutic feeds. PMID- 26996198 TI - The lifestyle of memory CD8(+) T cells. PMID- 26996200 TI - Maintenance of memory T cells in the bone marrow: survival or homeostatic proliferation? PMID- 26996201 TI - Open-source image reconstruction of super-resolution structured illumination microscopy data in ImageJ. AB - Super-resolved structured illumination microscopy (SR-SIM) is an important tool for fluorescence microscopy. SR-SIM microscopes perform multiple image acquisitions with varying illumination patterns, and reconstruct them to a super resolved image. In its most frequent, linear implementation, SR-SIM doubles the spatial resolution. The reconstruction is performed numerically on the acquired wide-field image data, and thus relies on a software implementation of specific SR-SIM image reconstruction algorithms. We present fairSIM, an easy-to-use plugin that provides SR-SIM reconstructions for a wide range of SR-SIM platforms directly within ImageJ. For research groups developing their own implementations of super-resolution structured illumination microscopy, fairSIM takes away the hurdle of generating yet another implementation of the reconstruction algorithm. For users of commercial microscopes, it offers an additional, in-depth analysis option for their data independent of specific operating systems. As a modular, open-source solution, fairSIM can easily be adapted, automated and extended as the field of SR-SIM progresses. PMID- 26996199 TI - Human RAG mutations: biochemistry and clinical implications. AB - The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate the V(D)J recombination process, which ultimately enables the generation of T cells and B cells with a diversified repertoire of antigen-specific receptors. Mutations of the RAG genes in humans are associated with a broad spectrum of clinical phenotypes, ranging from severe combined immunodeficiency to autoimmunity. Recently, novel insights into the phenotypic diversity of this disease have been provided by resolving the crystal structure of the RAG complex, by developing novel assays to test recombination activity of the mutant RAG proteins and by characterizing the molecular and cellular basis of immune dysregulation in patients with RAG deficiency. PMID- 26996202 TI - Room-temperature local ferromagnetism and its nanoscale expansion in the ferromagnetic semiconductor Ge(1-x)Fex. AB - We investigate the local electronic structure and magnetic properties of the group-IV-based ferromagnetic semiconductor, Ge(1-x)Fex (GeFe), using soft X-ray magnetic circular dichroism. Our results show that the doped Fe 3d electrons are strongly hybridized with the Ge 4p states, and have a large orbital magnetic moment relative to the spin magnetic moment; i.e., morb/mspin ~ 0.1. We find that nanoscale local ferromagnetic regions, which are formed through ferromagnetic exchange interactions in the high-Fe-content regions of the GeFe films, exist even at room temperature, well above the Curie temperature of 20-100 K. We observe the intriguing nanoscale expansion of the local ferromagnetic regions with decreasing temperature, followed by a transition of the entire film into a ferromagnetic state at the Curie temperature. PMID- 26996203 TI - Characterization of the Plasmodium Interspersed Repeats (PIR) proteins of Plasmodium chabaudi indicates functional diversity. AB - Plasmodium multigene families play a central role in the pathogenesis of malaria. The Plasmodium interspersed repeat (pir) genes comprise the largest multigene family in many Plasmodium spp. However their function(s) remains unknown. Using the rodent model of malaria, Plasmodium chabaudi, we show that individual CIR proteins have differential localizations within infected red cell (iRBC), suggesting different functional roles in a blood-stage infection. Some CIRs appear to be located on the surface of iRBC and merozoites and are therefore well placed to interact with host molecules. In line with this hypothesis, we show for the first time that a subset of recombinant CIRs bind mouse RBCs suggesting a role for CIR in rosette formation and/or invasion. Together, our results unravel differences in subcellular localization and ability to bind mouse erythrocytes between the members of the cir family, which strongly suggest different functional roles in a blood-stage infection. PMID- 26996204 TI - Autonomous pump against concentration gradient. AB - Using non-equilibrium molecular dynamics and Monte Carlo methods, we have studied the molecular transport in asymmetric nanochannels. The efficiency of the molecular pump depends on the angle and apertures of the asymmetric channel, the environmental temperature and average concentration of the particles. The pumping effect can be explained as the competition between the molecular force field and the thermal disturbance. Our results provide a green approach for pumping fluid particles against the concentration gradient through asymmetric nanoscale thin films without any external forces. It indicates that pumping vacuum can be a spontaneous process. PMID- 26996205 TI - Excessive daytime sleepiness and antipathogen drug consumption in the elderly: a test of the immune theory of sleep. AB - The evolutionary reasons for sleep remain controversial. The immune theory of sleep suggests that sleep is essential to the immune system, allowing organisms to allocate more energy to their immunity. This hypothesis was tested by exploring the links between excessive daytime sleepiness (EDS) and vulnerability to infectious diseases in a large (n = 9294) cohort of elderly individuals, with information on socio-demographics, daily habits, and medical characteristics. At the two-year and four-year follow-ups, we obtained individual data from the national healthcare insurance about all medications prescribed to the participants between 2001 and 2003 (n = 2865). We found an independent positive association between EDS and the consumption of some anti-pathogen drugs. This relationship was mostly explained by fungal and parasitic infections rather than by viral and bacterial ones. These results, although based on correlations, are consistent with the idea that EDS as a proxy of altered sleep quality/quantity may affect the efficiency of the immune system, and hence vulnerability to infections. PMID- 26996206 TI - The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes. AB - To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance. PMID- 26996207 TI - Quantification of HER2 heterogeneity in breast cancer-implications for identification of sub-dominant clones for personalised treatment. AB - Breast cancer is a heterogeneous disease, at both an inter- and intra-tumoural level. Appreciating heterogeneity through the application of biomarkers and molecular signatures adds complexity to tumour taxonomy but is key to personalising diagnosis, treatment and prognosis. The extent to which heterogeneity exists, and its interpretation remains a challenge to pathologists. Using HER2 as an exemplar, we have developed a simple reproducible heterogeneity index. Cell-to-cell HER2 heterogeneity was extensive in a proportion of both reported 'amplified' and 'non-amplified' cases. The highest levels of heterogeneity objectively identified occurred in borderline categories and higher ratio non-amplified cases. A case with particularly striking heterogeneity was analysed further with an array of biomarkers in order to assign a molecular diagnosis. Broad biological complexity was evident. In essence, interpretation, depending on the area of tumour sampled, could have been one of three distinct phenotypes, each of which would infer different therapeutic interventions. Therefore, we recommend that heterogeneity is assessed and taken into account when determining treatment options. PMID- 26996209 TI - Gastroschisis with gastric perforation and jejunal stenosis. A rare association of anomalies. AB - AIM: Gastroschisis with prenatal gastric perforation and intestinal stenosis is a rare and serious anomaly. although there are several case reports, no case series exists to suggest the prognosis for these infants. MATERIAL AND METHODS: In this report a case of gastroschisis with gastric perforation and jejunal stenosis in male newborn is presented with literature review. The stomach, small bowel and the part of the colon were herniated through the abdominal wall defect. A large perforation site at the anterior wall of fundus and a thin fibrous strip that causing stenosis of jejunum was found. RESULTS: Gastrorraphy was performed. Stenosis of jejunum was resected and t-t anastomosis was performed, followed by primary fascial closure. DISCUSSION: The prenatal sonographic finding of bowel or gastric perforation are variable. Antenatal bowel dilatation and in particular intraabdominal bowel dilatation is prognostically useful for detection of patients with worse outcome. The absence of bowel dilatation cannot fully exclude complex patients. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure are not associated with prolonged time for full enteral feeding and length of hospital stay. CONCLUSIONS: We have presented the first detailed report of surgical intervention and outcomes in case of gastroschisis with prenatal gastric perforation and congenital jejunal stenosis. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure is recommended here. More research should be focused to predict complex gastroschisis and to improve prenatal diagnosis and postnatal management, without a significant increase in morbidity and mortality. KEY WORDS: Gastroschisis, Gastric perforation, Stenosis of jejunum. PMID- 26996210 TI - Research Advances in Molecular Mechanisms of the Invasion and Metastasis of Lung Cancer. AB - The basic way of invasion and metastasis of lung cancer is that the tumor cells shed in the extracellular matrix, invade the basement membrane and the surrounding tissue, infiltrate into blood flow, and then survive and transport via the blood flow. After having been extravasated, migrated and arrested in the distant site, they finally form a metastatic lesion. Some basic mechanisms are required in these steps, such as tumor stem cells, diffusion and activity of tumor cells, escaping from apoptosis, angiogenesis and lymphangiogenesis, infiltration into blood flow, circulation and exudation, and distant metastasis proliferation. A better understanding of the mechanisms of the invasion and metastasis of lung cancer will facilitate the prevention and treatment of lung cancer. PMID- 26996208 TI - Deletion of Galectin-3 Enhances Xenobiotic Induced Murine Primary Biliary Cholangitis by Facilitating Apoptosis of BECs and Release of Autoantigens. AB - Galectin-3 (Gal-3) is a carbohydrate binding lectin, with multiple roles in inflammatory diseases and autoimmunity including its antiapoptotic effect on epithelial cells. In particular, increased expression of Gal-3 in epithelial cells is protective from apoptosis. Based on the thesis that apoptosis of biliary epithelial cells (BECs) is critical to the pathogenesis of Primary Biliary Cholangitis (PBC), we have analyzed the role of Gal-3 in the murine model of autoimmune cholangitis. We took advantage of Gal-3 knockout mice and immunized them with a mimotope of the major mitochondrial autoantigen of PBC, 2-octynoic acid (2-OA) coupled to BSA (2OA-BSA) and evaluated the natural history of subsequent disease, compared to control wild-type mice, by measuring levels of antibodies to PDC-E2, immunohistology of liver, and expression of Gal-3. We report herein that deletion of Gal-3 significantly exacerbates autoimmune cholangitis in these mice. This is manifested by increased periportal infiltrations, bile duct damage, granulomas and fibrosis. Interestingly, the BECs of Gal-3 knockout mice had a higher response to apoptotic stimuli and there were more pro-inflammatory lymphocytes and dendritic cells (DCs) in the livers of Gal 3 knockout mice. In conclusion, Gal-3 plays a protective role in the pathways that lead to the inflammatory destruction of biliary epithelial cells. PMID- 26996211 TI - Pathological Changes of von Economo Neuron and Fork Neuron in Neuropsychiatric Diseases. AB - von Economo neuron (VEN) is a bipolar neuron characterized by a large spindle shaped soma. VEN is generally distributed in the layer V of anterior insular lobe and anterior cingulate cortex. Fork neuron is another featured bipolar neuron. In recent years,many studies have illustrated that VEN and fork neurons are correlated with complicated cognition such as self-consciousness and social emotion. Studies in the development and morpholigies of these two neurons as well as their pathological changes in various neurological and psychiatric disorders have found that the abnormal number and functions of VEN can cause corresponding dysfunctions in social recognition and emotions both during the neuro developmental stages of childhood and during the nerve degeneration in old age stage. Therefore, more attentions should be paid on the research of VEN and fork neurons in neuropsychiatric diseases. PMID- 26996215 TI - Perovskite Solar Cells Based on Low-Temperature Processed Indium Oxide Electron Selective Layers. AB - Indium oxide (In2O3) as a promising n-type semiconductor material has been widely employed in optoelectronic applications. In this work, we applied low-temperature solution-processed In2O3 nanocrystalline film as an electron selective layer (ESL) in perovskite solar cells (PSCs) for the first time. By taking advantages of good optical and electrical properties of In2O3 such as high mobility, wide band gap, and high transmittance, we obtained In2O3-based PSCs with a good efficiency exceeding 13% after optimizing the concentration of the precursor solution and the annealing temperature. Furthermore, to enhance the performance of the In2O3-based PSCs, a phenyl-C61-butyric acid methyl ester (PCBM) layer was introduced to modify the surface of the In2O3 film. The PCBM film could fill up the pinholes or cracks along In2O3 grain boundaries to passivate the defects and make the ESL extremely compact and uniform, which is conducive to suppressing the charge recombination. As a result, the efficiency of the In2O3-based PSC was improved to 14.83% accompanied with V(OC), J(SC), and FF being 1.08 V, 20.06 mA cm(-2), and 0.685, respectively. PMID- 26996216 TI - Ministry of Health Clinical Practice Guidelines: Prevention, Diagnosis and Management of Tuberculosis. AB - The Ministry of Health (MOH) has developed the clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis to provide doctors and patients in Singapore with evidence-based treatment for tuberculosis. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis, for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guideline /cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines. PMID- 26996218 TI - Heating Two Types of Enriched Margarine: Complementary Analysis of Phytosteryl/Phytostanyl Fatty Acid Esters and Phytosterol/Phytostanol Oxidation Products. AB - Two phytosteryl and/or phytostanyl fatty acid ester-enriched margarines were subjected to common heating procedures. UHPLC-APCI-MS analysis resulted for the first time in comprehensive quantitative data on the decreases of individual phytosteryl/-stanyl fatty acid esters upon heating of enriched foods. These data were complemented by determining the concurrently formed phytosterol/-stanol oxidation products (POPs) via online LC-GC. Microwave-heating led to the least decreases of esters of approximately 5% in both margarines. Oven-heating of the margarine in a casserole caused the greatest decreases, with 68 and 86% esters remaining, respectively; the impact on individual esters was more pronounced with increasing degree of unsaturation of the esterified fatty acids. In the phytosteryl/-stanyl ester-enriched margarine, approximately 20% of the ester losses could be explained by the formation of POPs; in the phytostanyl ester enriched margarine, the POPs accounted for <1% of the observed ester decreases. PMID- 26996219 TI - Predicting Colonoscopy Time: A Quality Improvement Initiative. AB - BACKGROUND/AIMS: There is lack of consensus on the optimal time allotted for colonoscopy, which increases patient wait times. Our aim was to identify and quantify the individual pre-procedural factors that determine the total procedure time (TPT) of colonoscopy. METHODS: This retrospective study involved 4,494 subjects, undergoing outpatient colonoscopy. Effects of age, sex, body mass index, abdominal surgery history, procedure indication (screening, surveillance, or diagnostic), procedure session (morning or afternoon), and endoscopist's experience (fellow or attending) on TPT were evaluated using multiple regression analysis. A p<0.05 was considered significant. RESULTS: A total of 1,239 subjects satisfied the inclusion/exclusion criteria. Women, older individuals, and those with a history of abdominal surgery were found to have a shorter TPT (p>0.05) as did afternoon session colonoscopies (p=0.004). Less experienced endoscopists had longer TPTs (p>0.05). Screening (p=0.01) and surveillance (p=0.008) colonoscopies had a longer TPT than diagnostic procedures. Overall, the F-value of the regression model was 0.0009. CONCLUSIONS: The indication for colonoscopy and the time of day have statistically significant associations with TPT. These results will help in streamlining workflow, reduce wait time, and improve patient satisfaction. PMID- 26996220 TI - Feedback Survey of the Effect, Burden, and Cost of the National Endoscopic Quality Assessment Program during the Past 5 Years in Korea. AB - BACKGROUND/AIMS: In Korea, the nationwide gastric cancer screening program recommends biennial screening for individuals aged 40 years or older by way of either an upper gastrointestinal series or endoscopy. The national endoscopic quality assessment (QA) program began recommending endoscopy in medical institutions in 2009. We aimed to assess the effect, burden, and cost of the QA program from the viewpoint of medical institutions. METHODS: We surveyed the staff of institutional endoscopic units via e-mail. RESULTS: Staff members from 67 institutions replied. Most doctors were endoscopic specialists. They responded as to whether the QA program raised awareness for endoscopic quality (93%) or improved endoscopic practice (40%). The percentages of responders who reported improvements in the diagnosis of gastric cancer, the qualifications of endoscopists, the quality of facilities and equipment, endoscopic procedure, and endoscopic reprocessing were 69%, 60%, 66%, 82%, and 75%, respectively. Regarding reprocessing, many staff members reported that they had bought new automated endoscopic preprocessors (3%), used more disinfectants (34%), washed endoscopes longer (28%), reduced the number of endoscopies performed to adhere to reprocessing guidelines (9%), and created their own quality education programs (59%). Many responders said they felt that QA was associated with some degree of burden (48%), especially financial burden caused by purchasing new equipment. Reasonable quality standards (45%) and incentives (38%) were considered important to the success of the QA program. CONCLUSIONS: Endoscopic quality has improved after 5 years of the mandatory endoscopic QA program. PMID- 26996221 TI - The long-term risk of recognized and unrecognized myocardial infarction for depression in older men. AB - BACKGROUND: The association between myocardial infarction (MI) and depression is well described. Yet, the underlying mechanisms are unclear and the contribution of psychological factors is uncertain. We aimed to determine the risk of recognized (RMI) and unrecognized (UMI) myocardial infections on depression, as both have a similar impact on cardiovascular health but differ in psychological epiphenomena. METHOD: Participants of the Rotterdam Study, 1823 men aged ?55 years, were followed for the occurrence of depression. RMI and UMI were ascertained using electrocardiography and medical history at baseline. We determined the strength of the association of RMI and UMI with mortality, and we studied the relationship of RMI and UMI with depressive symptoms and the occurrence of major depression. RESULTS: The risk of mortality was similar in men with RMI [adjusted hazard ratio (aHR) 1.71, 95% confidence interval (CI) 1.45 2.03] and UMI (aHR 1.58, 95% CI 1.27-1.97). Men with RMI had on average [unstandardized regression coefficient (B) 1.14, 95% CI 0.07-2.21] higher scores for depressive symptoms. By contrast, we found no clear association between UMI and depressive symptoms (B 0.55, 95% CI -0.51 to 1.62) in men. Analysis including occurrence of major depression as the outcome were consistent with the pattern of association. CONCLUSION: The discrepant association of RMI and UMI with mortality compared to depression suggests that the psychological burden of having experienced an MI contributes to the long-term risk of depression. PMID- 26996223 TI - Fetal Intra-Peritoneal Transfusion for the Management of Very Early Spontaneous Twin Anemia-Polycythemia Sequence in an Obese Patient With a Whole Anterior Placenta. AB - Twin anemia-polycythemia sequence (TAPS) is a rare condition in monochorionic twin pregnancies. Small intertwin placental vascular communications allow transfusion, which results in a hemoglobin difference in the twins in the absence of oligohydramnios or polyhydramnios. We report here a case of TAPS diagnosed at 17 weeks' gestation in an obese patient (BMI 42) with a whole anterior placenta. The only possible treatment at this stage of pregnancy was intra-uterine transfusion (IUT), which was repeated weekly until photocoagulation of placental anastomoses was feasible. Fetoscopic laser surgery is the only curative treatment, but is challenging in TAPS because of the absence of polyhydramnios and the presence of minuscule anastomoses. An anterior placenta and high BMI can make the procedure even more challenging. This case report demonstrates that very early and rapidly progressing TAPS with technically complicated conditions (elevated BMI and anterior placenta) can be successfully managed with IUT until laser procedure is achievable. PMID- 26996224 TI - Finnish Twin Research in the 1930s: Contributions of Arvo Lehtovaara and His Mentor, Eino Kaila. AB - We offer a brief sketch of an overlooked early twin researcher, Arvo Johannes Lehtovaara (1905-1985), Professor of Psychology at the University of Jyvaskyla, 1939-1952, and the University of Helsinki, 1952-1970, with background notes on his mentor, Eino Kaila. PMID- 26996228 TI - Increased intake of fruits and vegetables in overweight subjects: effects on body weight, body composition, metabolic risk factors and dietary intake. AB - A diet rich in fruits and vegetables has been associated with several health benefits. However, the effects on body weight (BW) and metabolic markers are not fully known. The present study investigated the effects of increased intake of fruits and vegetables in overweight and obese men and women on dietary habits, anthropometry and metabolic control. In a 16-week controlled intervention, thirty four men and thirty-four women aged 35-65 years (BMI>27 kg/m2) were randomised to an intervention (IN) or a reference (RG) group. All participants received general dietary advice, and subjects in the IN group received fruits and vegetables for free, of which >=500 g had to be eaten daily. BW, waist circumference (WC), sagittal abdominal diameter (SAD), plasma insulin, blood glucose, glycated Hb (HbA1c), serum lipids, blood pressure, plasminogen activator inhibitor-1 activity, urinary isoprostane (iso-8-PGF 2alpha) and serum carotenoids were measured. Diet was assessed using 3-d weighed food records. In all, thirty subjects in the IN group and thirty-two in the RG group completed the intervention. Intake of fruits and vegetables doubled in the IN group, whereas intake of fruits increased in the RG group. Serum alpha- and beta-carotene concentrations and intakes of folate and vitamin C increased significantly in the IN group. Energy intake, BW, WC and SAD decreased significantly in both groups. Supine systolic blood pressure decreased significantly in the IN group, with no between-group differences. No significant changes were observed for other metabolic markers. Provision of fruits and vegetables led to substantially increased intakes, with subsequent favourable changes in anthropometry and insulin levels, which tended to be more pronounced in the IN group. The observed improvements may, in combination with improved nutritional markers, have health benefits in the long term. PMID- 26996229 TI - Impulsivity is predicted by the thinness of the insular cortex in rats. PMID- 26996230 TI - Bacterial physiology: (p)ppGpp target ribosome assembly. PMID- 26996231 TI - Induced Cell-Based Transplantation to Therapeutically Target Spinal Cord Disorders. PMID- 26996222 TI - Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project. AB - We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI. PMID- 26996232 TI - Metaboloepigenetics: the Emerging Network in Stem Cell Homeostasis Regulation. AB - Epigenetics harbours all regulatory information that, beyond nucleotide sequences, allows cells to "make decisions" throughout their lifetime in response to the external environment. The information can be transitory or relatively stable, and is even transmittable either to daughter cells or to the next generations through the germ line. Recent discoveries shed light on numerous connections between metabolites and epigenetic chromatin-modifying enzymes, providing a link between the metabolic state of the cell and epigenetics, and ultimately between metabolism, gene expression and cell fate. In this review, we discuss the possible connections between metabolism and epigenetic regulation of stem cell differentiation and self-renewal. Moreover, we describe pertinent literature that could explain how altered metabolic state and nutrition can contribute to disease development through epigenetic modifications. A special section is dedicated to the emerging link between the circadian clock, metabolic transcriptional regulation by epigenetic mechanisms and their implication in stem cell homeostasis. PMID- 26996233 TI - Morphologic changes within the cerebellar cortex in the unilateral 6 hydroxydopamine lesioned rat model for Parkinson disease. AB - Parkinson's disease (PD) is a common neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra. Most investigations have focused on the cerebral regions such as the basal ganglia, thalamus, or the substantia nigra, but whether there is pathologic impairment within the cerebellum has rarely been assessed. Synapsin and neurofilament as the inner markers of neurons and synapses reflect the functional state by their distribution or expression. Significant morphologic changes at the cellular level have been demonstrated directly or indirectly in multiple neurodegenerative diseases. The purpose of this study was to determine whether the behavioral abnormalities that accompany PD are associated with the cerebellum using an in vivo 6-hydroxydopamine lesioned rat model. Forty-two rats were divided into three groups, the Parkinsonian group (N=22), sham group (N=10) and control group (N=10). The dopaminergic lesion was determined by immunohistochemical analysis for tyrosine hydroxylase-immunopositive cells. Immunohistochemical studies showed that the density of synapsin I in the granular layer of the cerebellum on both sides of the Parkinsonian -model was not statistically significantly different compared to the control and sham groups. However, expression of neurofilament H in the cortex within bilateral paramedian lobule (PML) and Crus 2 of the ansiform lobule (C2AL) in cerebellum posterior lobe of Parkinsonian rats was decreased compared with controls (P<0.05), especially in the loss of Purkinje cells and the presence of morphologic abnormalities in the cell nucleus. The study suggested that loss of neurons and synapses may take place in the cerebellar cortex of Parkinson's disease, and might play an important role in the pathologic mechanism of PD. PMID- 26996234 TI - Nonlinear optomechanical measurement of mechanical motion. AB - Precision measurement of nonlinear observables is an important goal in all facets of quantum optics. This allows measurement-based non-classical state preparation, which has been applied to great success in various physical systems, and provides a route for quantum information processing with otherwise linear interactions. In cavity optomechanics much progress has been made using linear interactions and measurement, but observation of nonlinear mechanical degrees-of-freedom remains outstanding. Here we report the observation of displacement-squared thermal motion of a micro-mechanical resonator by exploiting the intrinsic nonlinearity of the radiation-pressure interaction. Using this measurement we generate bimodal mechanical states of motion with separations and feature sizes well below 100 pm. Future improvements to this approach will allow the preparation of quantum superposition states, which can be used to experimentally explore collapse models of the wavefunction and the potential for mechanical-resonator-based quantum information and metrology applications. PMID- 26996235 TI - Histone Deacetylase 8: Characterization of Physiological Divalent Metal Catalysis. AB - Histone deacetylases (HDACs) are responsible for the removal of acetyl groups from histones, resulting in gene silencing. Overexpression of HDACs is associated with cancer, and their inhibitors are of particular interest as chemotherapeutics. However, HDACs remain a target of mechanistic debate. HDAC class 8 is the most studied HDAC, and of particular importance due to its human oncological relevance. HDAC8 has traditionally been considered to be a Zn dependent enzyme. However, recent experimental assays have challenged this assumption and shown that HDAC8 is catalytically active with a variety of different metals, and that it may be a Fe-dependent enzyme in vivo. We studied two opposing mechanisms utilizing a series of divalent metal ions in physiological abundance (Zn(2+), Fe(2+), Co(2+), Mn(2+), Ni(2+), and Mg(2+)). Extensive sampling of the entire protein with different bound metals was done with the mixed quantum-classical QM/DMD method. Density functional theory (DFT) on an unusually large cluster model was used to describe the active site and reaction mechanism. We have found that the reaction profile of HDAC8 is similar among all metals tested, and follows one of the previously published mechanisms, but the rate-determining step is different from the one previously claimed. We further provide a scheme for estimating the metal binding affinities to the protein. We use the quantum theory of atoms in molecules (QTAIM) to understand the different binding affinities for each metal in HDAC8 as well as the ability of each metal to bind and properly orient the substrate for deacetylation. The combination of this data with the catalytic rate constants is required to reproduce the experimentally observed trend in metal-depending performance. We predict Co(2+) and Zn(2+) to be the most active metals in HDAC8, followed by Fe(2+), and Mn(2+) and Mg(2+) to be the least active. PMID- 26996236 TI - The miR-20-Rest-Wnt signaling axis regulates neural progenitor cell differentiation. AB - Increasing evidence suggests that three dimensional (3-D) cell cultures are an improvement over traditional two dimensional (2-D) cell cultures. Current researches have extensively focused on the study of utilizing biomaterial-based 3 D culture systems to study and direct stem-cell fate both in vitro and in vivo. Here in our study, we screened the differential expression patterns of miRNAs between 2-D cultured and 3-D cultured NPCs using microarray analysis. Among these differentially expressed miRNAs, miR-20 was found to increase during differentiation of NPCs. Specifically, the facilitative effect on neural differentiation of miR-20 is mediated, at least in part by directly target the Rest gene, which is essential for preventing neural differentiation and maintaining NPCs self-renewal. Furthermore, the expression of miR-20 was decreased when the WNT pathway was inhibited by knock down of beta-catenin or by exogenous Dkk protein, whereas it increased when the WNT pathway was activated by exogenous Wnt3a protein. Overall, miR-20, Rest and Wnt signaling are suggested to be involved in a regulatory circuit that can modulate the neural differention of NPCs. This novel regulatory circuit provides additional insight into how microRNAs interact with signaling molecules during neural differentiation of NPCs, allowing for fine-tuning of intricate cellular processes. PMID- 26996238 TI - [Training of medical students for pelvic examination: Benefits of teaching on anatomic models]. AB - OBJECTIVES: To evaluate the benefits of training sessions for pelvic examination using anatomic models. MATERIAL AND METHODS: The medical students (MS) registered in their 5th year of medical studies at Angers University Hospital had to complete two anonymous questionnaires; one at the beginning of the workshop and one at the end. Every procedure which included pelvic exam (PE), vaginal sample (VS), smear test (ST), insertion of a speculum and insertion of intra-uterine device (IUD) was evaluated. RESULTS: Seventy-one MS answered both questionnaires. They were very satisfied or satisfied with the outcomes of the workshop in 91 % of the cases. At the beginning of the workshop, 28 %, 52 %, 30 %, 25 % and 3 % reported a low level of difficulty to carry out, respectively, a PE, VS, ST, insertion of a speculum, insertion of an IUD. At the end of the session, there were respectively 55 %, 83 %, 76 %, 66 % and 16 % of MS to report a low level of difficulty of these same procedures. For all of these procedures, there were a significant (P<0.05) number of MS who estimated the procedure's level of difficulty as being low at the end of the session. CONCLUSION: The level of technical difficulty of all procedures was significantly decreased at the end of the workshop. PMID- 26996237 TI - Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis. AB - Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti Wolbachia consortium (A.WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25-40 mg/Kg regimen is bioequivalent to a clinically effective 100-200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis. PMID- 26996239 TI - [Episiotomy in France in 2010: Variations according to obstetrical context and place of birth]. AB - OBJECTIVES: To analyze episiotomy rates according to the characteristics of women and maternity units and to study the variability of rates between units and regions. MATERIALS AND METHODS: Our study included all vaginal deliveries in the National Perinatal Survey 2010 (n=11,322). We estimated the adjusted relative risk of episiotomy (aRR) according to women and maternity units characteristics, and we studied the variance between regions and hospitals using multilevel Poisson regressions, stratified on parity. RESULTS: In 2010, 44.7% of primiparous; 14.2% in multiparous had an episiotomy. The main associated factors were Asian origin (primiparae: aRR=1.32 [1.16-1.51]; multiparae: aRR=2.30 [1.67 3.16]), breech presentation (primiparae: aRR=2.14 [1.87-2.21]; multiparae: aRR=3.32 [2.52-4.38]) and operative vaginal delivery (primiparae: aRR=2.04 [1.89 2.11]; multiparae: aRR=3.19 [2.74-3.72]). Rates varied dramatically between regions (primiparae: 17 to 64%; multiparae: 3 to 21%). The variance was significant between regions and between maternity units after controlling for women and units characteristics. CONCLUSION: It would be useful to study the attitudes and views of obstetricians and midwives about the protection of the perineum to better understand these differences in practice. PMID- 26996241 TI - Synthesis and Anti-HIV-1 Evaluation of Some Novel MC-1220 Analogs as Non Nucleoside Reverse Transcriptase Inhibitors. AB - Some novel MC-1220 analogs were synthesized by condensation of 4,6-dichloro-N methylpyrimidin-2-amine derivatives (1a,b and 15) and/or 4-chloro-6-methoxy-N,N,5 trimethylpyrimidin-2-amine (2a) with the sodium salt of 2,6 difluorophenylacetonitrile followed by treatment with aqueous sodium hydroxide in methanol, alkylation, reduction, halogenation, and/or acidic hydrolysis. All synthesized compounds were evaluated for their activity against HIV-1. The most active compound in this study was compound 7, which showed activity against HIV-1 comparable to that of MC-1220. The only difference in structure between compound 7 and MC-1220 is a fluoro atom instead of a CH3 group. PMID- 26996240 TI - Acid-sensing ion channel 1a contributes to hippocampal LTP inducibility through multiple mechanisms. AB - The exact roles of acid-sensing ion channels (ASICs) in synaptic plasticity remain elusive. Here, we address the contribution of ASIC1a to five forms of synaptic plasticity in the mouse hippocampus using an in vitro multi-electrode array recording system. We found that genetic deletion or pharmacological blockade of ASIC1a greatly reduced, but did not fully abolish, the probability of long-term potentiation (LTP) induction by either single or repeated high frequency stimulation or theta burst stimulation in the CA1 region. However, these treatments did not affect hippocampal long-term depression induced by low frequency electrical stimulation or (RS)-3,5-dihydroxyphenylglycine. We also show that ASIC1a exerts its action in hippocampal LTP through multiple mechanisms that include but are not limited to augmentation of NMDA receptor function. Taken together, these results reveal new insights into the role of ASIC1a in hippocampal synaptic plasticity and the underlying mechanisms. This unbiased study also demonstrates a novel and objective way to assay synaptic plasticity mechanisms in the brain. PMID- 26996243 TI - Short-term postoperative distress associated with open vs. transoral robotic surgery (TORS) in patients with T1-T2 carcinomas of the tongue base and supraglottis. AB - BACKGROUND: This study compared the adverse effects of open surgery (OS) including lateral pharyngotomy and supraglottic laryngectomy vs. transoral robotic surgery (TORS) in the treatment of stage T1 and T2 carcinomas of the tongue base and supraglottis. METHODS: A retrospective study involving a 49 (13 female and 36 male) patients with untreated T1 or T2 carcinomas. Twenty two were operated on using TORS and 27 underwent conventional OS. The indicators for comparison were: total blood loss during surgery, post-operative pain measured with the Visual Analog Scale (VAS); global, emotional and physical post operational states assessed with the standardized M.D. Anderson Dysphagia Inventory (MDADI) and psychosocial distress (PD) questionnaire. Apart from blood loss, subjective symptoms were evaluated 1 and 6 weeks and 6 months after surgery. The differences in indicators between groups were analyzed using Fisher's Least Significant Difference (LSD) test at the 5% significance level. RESULTS: Mean general OS and TORS associated blood loss were 405 and 29 ml, respectively. The mean MDADI score in TORS vs. OS patients one week, six weeks and six months postoperatively was 60.01 vs. 44.93, 91.01 vs. 62.19 and 94.18 vs. 93.56. The mean VAS score in the TORS vs. OS group at the same time intervals were 5.09 vs. 5.56, 2.09 vs. 3.11 and 1.27 vs. 1.33. All differences between TORS and OS were statistically significant with the exception of 6 month values for particular scores. The mean PD score in TORS vs. OS patients in one week, six weeks and 6 months was 26.82 vs. 25.11, 39.95 vs. 29.22 and 44.73 vs. 44.52. Only the six week distinctions were significant. The both methods were comparable in terms of the risk of locoregional tumour recurrence. CONCLUSIONS: The study confirmed the assumption of the TORS as a minimally invasive procedure significantly reducing the intraoperative blood loss, pain, swallowing and psychosocial distress as late as 6 weeks postoperatively in patients with early staged carcinomas of the tongue base and supraglottis. PMID- 26996242 TI - Proteomic approaches to the study of renal mitochondria. AB - BACKGROUND AND AIMS: Dysfunction of kidney mitochondria plays a critical role in the pathogenesis of a number of renal diseases. Proteomics represents an untargeted attempt to reveal the remodeling of mitochondrial proteins during disease. Combination of separation methods and mass spectrometry allows identification and quantitative analysis of mitochondrial proteins including protein complexes. The aim of this review is to summarize the methods and applications of proteomics to renal mitochondria. METHODS: Using keywords "mitochondria", "kidney", "proteomics", scientific databases (PubMed and Web of knowledge) were searched from 2000 to August 2015 for articles describing methods and applications of proteomics to analysis of mitochondrial proteins in kidney. Included were publications on mitochondrial proteins in kidneys of humans and animal model in health and disease. RESULTS AND CONCLUSION: Proteomics of renal mitochondria has been/is mostly used in diabetes, hypertension, acidosis, nephrotoxicity and renal cancer. Integration of proteomics with other methods for examining protein activity is promising for insight into the role of renal mitochondria in pathological states. Several challenges were identified: selection of appropriate model organism, sensitivity of analytical methods and analysis of mitochondrial proteome in different renal zones/biopsies in the course of various kidney disorders. PMID- 26996244 TI - Impact of the representation of stomatal conductance on model projections of heatwave intensity. AB - Stomatal conductance links plant water use and carbon uptake, and is a critical process for the land surface component of climate models. However, stomatal conductance schemes commonly assume that all vegetation with the same photosynthetic pathway use identical plant water use strategies whereas observations indicate otherwise. Here, we implement a new stomatal scheme derived from optimal stomatal theory and constrained by a recent global synthesis of stomatal conductance measurements from 314 species, across 56 field sites. Using this new stomatal scheme, within a global climate model, subtantially increases the intensity of future heatwaves across Northern Eurasia. This indicates that our climate model has previously been under-predicting heatwave intensity. Our results have widespread implications for other climate models, many of which do not account for differences in stomatal water-use across different plant functional types, and hence, are also likely under projecting heatwave intensity in the future. PMID- 26996245 TI - Whole genome duplication in coast redwood (Sequoia sempervirens) and its implications for explaining the rarity of polyploidy in conifers. AB - Polyploidy is common and an important evolutionary factor in most land plant lineages, but it is rare in gymnosperms. Coast redwood (Sequoia sempervirens) is one of just two polyploid conifer species and the only hexaploid. Evidence from fossil guard cell size suggests that polyploidy in Sequoia dates to the Eocene. Numerous hypotheses about the mechanism of polyploidy and parental genome donors have been proposed, based primarily on morphological and cytological data, but it remains unclear how Sequoia became polyploid and why this lineage overcame an apparent gymnosperm barrier to whole-genome duplication (WGD). We sequenced transcriptomes and used phylogenetic inference, Bayesian concordance analysis and paralog age distributions to resolve relationships among gene copies in hexaploid coast redwood and close relatives. Our data show that hexaploidy in coast redwood is best explained by autopolyploidy or, if there was allopolyploidy, it happened within the Californian redwood clade. We found that duplicate genes have more similar sequences than expected, given the age of the inferred polyploidization. Conflict between molecular and fossil estimates of WGD can be explained if diploidization occurred very slowly following polyploidization. We extrapolate from this to suggest that the rarity of polyploidy in gymnosperms may be due to slow diploidization in this clade. PMID- 26996246 TI - Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study. AB - PURPOSE: Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up titration of the nifedipine gastrointestinal therapeutic system (GITS) with up titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. METHODS: This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. FINDINGS: Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. IMPLICATIONS: Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122. PMID- 26996251 TI - Palpitations in a 75-year-old woman. PMID- 26996250 TI - Reply letter to: HIPEC and nephrotoxicity: A cisplatin induced effect? PMID- 26996252 TI - Sub-micrometer Novolac-Derived Carbon Beads for High Performance Supercapacitors and Redox Electrolyte Energy Storage. AB - Carbon beads with sub-micrometer diameter were produced with a self-emulsifying novolac-ethanol-water system. A physical activation with CO2 was carried out to create a high microporosity with a specific surface area varying from 771 (DFT) to 2237 m(2)/g (DFT) and a total pore volume from 0.28 to 1.71 cm(3)/g. The carbon particles conserve their spherical shape after the thermal treatments. The controllable porosity of the carbon spheres is attractive for the application in electrochemical double layer capacitors. The electrochemical characterization was carried out in aqueous 1 M Na2SO4 (127 F/g) and organic 1 M tetraethylammonium tetrafluoroborate in propylene carbonate (123 F/g). Furthermore, an aqueous redox electrolyte (6 M KI) was tested with the highly porous carbon and a specific energy of 33 W.h/kg (equivalent to 493 F/g) was obtained. In addition to a high specific capacitance, the carbon beads also provide an excellent rate performance at high current and potential in all tested electrolytes, which leads to a high specific power (>11 kW/kg) with an electrode thickness of ca. 200 MUm. PMID- 26996253 TI - Doppler effect induced spin relaxation boom. AB - We study an electron spin qubit confined in a moving quantum dot (QD), with our attention on both spin relaxation, and the product of spin relaxation, the emitted phonons. We find that Doppler effect leads to several interesting phenomena. In particular, spin relaxation rate peaks when the QD motion is in the transonic regime, which we term a spin relaxation boom in analogy to the classical sonic boom. This peak indicates that a moving spin qubit may have even lower relaxation rate than a static qubit, pointing at the possibility of coherence-preserving transport for a spin qubit. We also find that the emitted phonons become strongly directional and narrow in their frequency range as the qubit reaches the supersonic regime, similar to Cherenkov radiation. In other words, fast moving excited spin qubits can act as a source of non-classical phonons. Compared to classical Cherenkov radiation, we show that quantum dot confinement produces a small but important correction on the Cherenkov angle. Taking together, these results have important implications to both spin-based quantum information processing and coherent phonon dynamics in semiconductor nanostructures. PMID- 26996254 TI - Higher-order Multivariable Polynomial Regression to Estimate Human Affective States. AB - From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects' affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain's motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states. PMID- 26996256 TI - Conditional Control of CRISPR/Cas9 Function. AB - The recently discovered CRISPR/Cas9 endonuclease system, comprised of a guide RNA for the recognition of a DNA target and the Cas9 nuclease protein for binding and processing the target, has been extensively studied and has been widely applied in genome editing, synthetic biology, and transcriptional modulation in cells and animals. Toward more precise genomic modification and further expansion of the CRISPR/Cas9 system as a spatiotemporally controlled gene regulatory system, several approaches of conditional activation of Cas9 function using small molecules and light have recently been developed. These methods have led to improvements in the genome editing specificity of the CRISPR/Cas9 system and enabled its activation with temporal and spatial precision. PMID- 26996257 TI - Comparison of retinal nerve fiber layer and macular thickness for discriminating primary open-angle glaucoma and normal-tension glaucoma using optical coherence tomography. AB - PURPOSE: The aim of this study was to evaluate the discrimination capabilities of macular and peripapillary retinal nerve fiber layer (pRNFL) thickness parameters as measured using spectral domain optical coherence tomography (SD-OCT) between primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). METHODS: A total of 90 subjects were enrolled: 30 healthy subjects, 30 subjects with POAG and 30 subjects with NTG, consecutively. Retinal nerve fiber layer thickness, macular thickness and volume measurements were obtained with circular and radial SD-OCT scans. All parameters were compared between groups using an analysis of variance test. Areas under receiver-operating characteristic (AROC) curves with sensitivities at specificities greater than or equal to 90 per cent were generated to compare discrimination capabilities of various parameters between POAG and NTG. RESULTS: Macular thickness and volume measurements were the highest in normal subjects, followed by NTG and POAG (p < 0.05). Average retinal nerve fiber layer thickness had perfect discrimination for normal-POAG (AROC: 1.000; sensitivity: 100 per cent) and near perfect discrimination for normal-NTG (AROC: 0.979; sensitivity: 93 per cent) as well as NTG-POAG pairs (AROC: 0.900; sensitivity: 60 per cent). Inferior outer macular thickness (IOMT) and total volume were the best macular thickness and volume parameters having similar AROCs and sensitivities between normal and POAG (IOMT, AROC: 0.987; sensitivity: 92 per cent and total volume, AROC: 0.997; sensitivity: 97 per cent), normal and NTG (IOMT, AROC: 0.862, sensitivity: 47 per cent and total volume, AROC: 0.898, sensitivity: 67 per cent) and also between NTG and POAG (IOMT, AROC: 0.910, sensitivity: 53 per cent and total volume, AROC: 0.922, sensitivity: 77 per cent). In each comparison group, there was no statistically significant difference in AROCs between average retinal nerve fiber layer and inferior outer macular thickness, as well as total volume. CONCLUSIONS: The macular parameters offer comparable performance to pRNFL parameters for the discrimination of NTG and POAG. Average retinal nerve fiber layer thickness, total macular volume and inferior outer macular thickness were the best SD-OCT parameters with superior discriminating capabilities. PMID- 26996258 TI - Production of nanotubes in delignified porous cellulosic materials after hydrolysis with cellulase. AB - In this study, tubular cellulose (TC), a porous cellulosic material produced by delignification of sawdust, was treated with a Trichoderma reesei cellulase in order to increase the proportion of nano-tubes. The effect of enzyme concentration and treatment duration on surface characteristics was studied and the samples were analyzed with BET, SEM and XRD. Also, a composite material of gelatinized starch and TC underwent enzymatic treatment in combination with amylase (320U) and cellulase (320U) enzymes. For TC, the optimum enzyme concentration (640U) led to significant increase of TC specific surface area and pore volume along with the reduction of pore diameter. It was also shown that the enzymatic treatment did not result to a significant change of cellulose crystallinity index. The produced nano-tubular cellulose shows potential for application to drug and chemical preservative delivery systems. PMID- 26996255 TI - Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease. AB - During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Abeta), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood-brain barrier function - conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Abeta deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease. PMID- 26996259 TI - Detoxification of acidic biorefinery waste liquor for production of high value amino acid. AB - The current study evaluates the detoxification of acid pretreatment liquor (APL) using adsorbent (ADS 400 & ADS 800) or ion-exchange (A-27MP & A-72MP) resins and its potential for amino acid production. The APL is generated as a by-product from the pretreatment of lignocellulosic biomass and is rich monomeric sugars as well as sugar degradation products (fermentation inhibitors) such as furfural and hydroxymethyl furfural (HMF). Of the four resins compared, ADS 800 removed approximately 85% and 60% of furfural and HMF, respectively. ADS 800 could be reused for up to six cycles after regeneration without losing its adsorption properties. The study was further extended by assessing the fermentability of detoxified APL for l-lysine production using wild and mutant strains of Corynebacterium glutamicum. The detoxified APL was superior to APL for l-lysine production. PMID- 26996260 TI - Breathable waveguides for combined light and CO2 delivery to microalgae. AB - Suboptimal light and chemical distribution (CO2, O2) in photobioreactors hinder phototrophic microalgal productivity and prevent economically scalable production of biofuels and bioproducts. Current strategies that improve illumination in reactors negatively impact chemical distribution, and vice versa. In this work, an integrated illumination and aeration approach is demonstrated using a gas permeable planar waveguide that enables combined light and chemical distribution. An optically transparent cellulose acetate butyrate (CAB) slab is used to supply both light and CO2 at various source concentrations to cyanobacteria. The breathable waveguide architecture is capable of cultivating microalgae with over double the growth as achieved with impermeable waveguides. PMID- 26996261 TI - Opportunity for high value-added chemicals from food supply chain wastes. AB - With approximately 1.3 billion tonnes of food wasted per annum, food supply chain wastes (FSCWs) may be viewed as the contemporary Periodic Table of biobased feedstock chemicals (platform molecules) and functional materials. Herein, the global drivers and case for food waste valorisation within the context of global sustainability, sustainable development goals and the bioeconomy are discussed. The emerging potential of high value added chemicals from certain tropical FSCW is considered as these are grown in three major geographical areas: Brazil, India and China, and likely to increase in volume. FSCW in the context of biorefineries is discussed and two case studies are reported, namely: waste potato, and; orange peel waste. Interestingly, both waste feedstocks, like many others, produce proteins and with the global demand for vegetable proteins on the rise then proteins from FSCW may become a dominant area. PMID- 26996262 TI - Utilization of municipal solid and liquid wastes for bioenergy and bioproducts production. AB - Municipal wastes, be it solid or liquid, are rising due to the global population growth and rapid urbanization and industrialization. Conventional management practice involving recycling, combustion, and treatment/disposal is deemed unsustainable. Solutions must be sought to not only increase the capacity but also improve the sustainability of waste management. Research has demonstrated that the non-recyclable waste materials and bio-solids can be converted into useable heat, electricity, or fuel and chemical through a variety of processes, including gasification, pyrolysis, anaerobic digestion, and landfill gas in addition to combustion, and wastewater streams have the potential to support algae growth and provide other energy recovery options. The present review is intended to assess and analyze the current state of knowledge in the municipal solid wastes and wastewater treatment and utilization technologies and recommend practical solution options and future research and development needs. PMID- 26996263 TI - Waste biorefineries using filamentous ascomycetes fungi: Present status and future prospects. AB - Filamentous ascomycetes fungi have had important roles in natural cycles, and are already used industrially for e.g. supplying of citric, gluconic and itaconic acids as well as many enzymes. Faster human activities result in higher consumption of our resources and producing more wastes. Therefore, these fungi can be explored to use their capabilities to convert back wastes to resources. The present paper reviews the capabilities of these fungi in growing on various residuals, producing lignocellulose-degrading enzymes and production of organic acids, ethanol, pigments, etc. Particular attention has been on Aspergillus, Fusarium, Neurospora and Monascus genera. Since various species are used for production of human food, their biomass can be considered for feed applications and so biomass compositional characteristics as well as aspects related to culture in bioreactor are also provided. The review has been further complemented with future research avenues. PMID- 26996264 TI - Increased matriptase zymogen activation by UV irradiation protects keratinocyte from cell death. AB - BACKGROUND: Overexposure to ultraviolet (UV) derived from solar light causes skin damage by causing DNA lesions and the generation of reactive oxygen species (ROS) in keratinocytes and other epidermal cells. The type 2 transmembrane serine protease matriptase has characteristics that allow keratinocytes to respond to/recover from, environmental insults to the skin. This response may depend on its roles in epidermal proliferation and early differentiation, and its rapid activation in response to changes in the cellular chemical milieu, including increased oxidative stress. OBJECTIVE: We investigate the regulation of matriptase activation and its role in the response of the skin to exposure to different parts of the UV spectrum including UVA UVB, and UVR. METHODS: The activation state and distribution of matriptase in ex vivo UV exposed human skin specimens and sun damaged skin samples were analyzed by immunohistochemistry. HaCaT immortalized human keratinocytes were also used to investigate the mechanism of matriptase zymogen activation induced by UV irradiation. Levels of cytosolic ROS were determined by H2DCF assay. Activated matriptase, PARP and caspase 3 cleavage was analyzed by Western blotting, and the apoptotic ratio was measured by Hoechst 33258 staining. RESULTS: UVB exposure rapidly increased matriptase zymogen activation in the basal keratinocytes of skin samples. Activated matriptase was also detected at much higher levels in both the basal and spinous layer keratinocytes in sun damaged skin with actinic elastosis. UVB and solar light-induced matriptase zymogen activation likely results from UV induced ROS generation, given that UVR, UVA, and UVB irradiation induced HaCaT human keratinocytes to activate matriptase in a dose- and time-dependent manner, and that this was suppressed by the ROS scavenger N-tert-butyl-alpha phenylnitrone and reducing agent dithiothreitol. Matriptase deficient HaCaT keratinocytes were more susceptible to UV-induced apoptosis than control cells, suggesting a protective role for matriptase in UV exposed keratinocytes. CONCLUSION: UV irradiation/ROS induced matriptase proteolysis may have short term protective effects and contribute to the recovery from acute epidermal damage and/or pathology of skin with chronic sun damage. PMID- 26996265 TI - A Processive Arabidopsis Formin Modulates Actin Filament Dynamics in Association with Profilin. AB - Formins are conserved regulators of actin cytoskeletal organization and dynamics that have been implicated to be important for cell division and cell polarity. The mechanism by which diverse formins regulate actin dynamics in plants is still not well understood. Using in vitro single-molecule imaging technology, we directly observed that the FH1-FH2 domain of an Arabidopsis thaliana formin, AtFH14, processively attaches to the barbed end of actin filaments as a dimer and slows their elongation rate by 90%. The attachment persistence of FH1-FH2 is concentration dependent. Furthermore, by use of the triple-color total internal reflection fluorescence microscopy, we found that ABP29, a barbed-end capping protein, competes with FH1-FH2 at the filament barbed end, where its binding is mutually exclusive with AtFH14. In the presence of different plant profilin isoforms, FH1-FH2 enhances filament elongation rates from about 10 to 42 times. Filaments buckle when FH1-FH2 is anchored specifically to cover slides, further indicating that AtFH14 moves processively on the elongating barbed end. At high concentration, AtFH14 bundles actin filaments randomly into antiparallel or parallel spindle-like structures; however, the FH1-FH2-mediated bundles become thinner and longer in the presence of plant profilins. This is the direct demonstration of a processive formin from plants. Our results also illuminate the molecular mechanism of AtFH14 in regulating actin dynamics via association with profilin. PMID- 26996266 TI - Credentialing of Australian and New Zealand infection control professionals: An exploratory study. AB - BACKGROUND: Despite evidence from overseas that certification and credentialing of infection control professionals (ICPs) is important to patient outcomes, there are no standardized requirements for the education and preparation of ICPs in Australia. A credentialing process (now managed by the Australasian College of Infection Prevention and Control) has been in existence since 2000; however, no evaluation has occurred. METHODS: A cross-sectional study design was used to identify the perceived barriers to credentialing and the characteristics of credentialed ICPs. RESULTS: There were 300 responses received; 45 (15%) of participants were credentialed. Noncredentialed ICPs identified barriers to credentialing as no employer requirement and no associated remuneration. Generally credentialed ICPs were more likely to hold higher degrees and have more infection control experience than their noncredentialed colleagues. CONCLUSIONS: The credentialing process itself may assist in supporting ICP development by providing an opportunity for reflection and feedback from peer review. Further, the process may assist ICPs in being flexible and adaptable to the challenging and ever-changing environment that is infection control. PMID- 26996267 TI - Risk factors for methicillin-resistant Staphylococcus aureus carriage among residents in 7 nursing homes in Shanghai, China. AB - BACKGROUND: Nursing home residents are a population at risk for methicillin resistant Staphylococcus aureus (MRSA) carriage, but few data about MRSA in this setting in Shanghai are available. The aim of this study is to determine the prevalence and risk factors for MRSA carriage in nursing home residents in Shanghai, China. METHODS: Four hundred forty-three residents from 7 nursing homes in Shanghai, China, participated in this study; nasal and axillary swabs were obtained from these residents. Laboratory identification for S aureus and antimicrobial susceptibility testing were performed when isolated. Data, including individual resident characteristics and nursing home characteristics, were collected and analyzed. RESULTS: Of the 443 participating residents, 99 (22.3%) and 45 (10.2%) residents were colonized by S aureus and MRSA, respectively. Previous hospitalization (odds ratio [OR], 2.564; 95% confidence interval [CI], 1.214-5.415; P = .014), presence of an invasive device (OR, 3.455; 95% CI, 1.678-7.113; P = .001), chloramphenicol therapy (OR, 7.672; 95% CI, 1.807 32.580; P = .006), and macrolides therapy (OR, 2.796; 95% CI, 1.056-7.403; P = .038) were independent risk factors for MRSA colonization. Low expenditure per month and less good sanitary condition also increased the risk for MRSA colonization. CONCLUSIONS: Our study suggests that nursing homes are significant reservoirs for MRSA. Implementation of infection control strategies must be given high priority in nursing homes to fight the high prevalence of MRSA, and increased convenience and feasibility should also be realized with these control strategies for MRSA colonization. PMID- 26996268 TI - Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations. AB - INTRODUCTION: Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. METHODS: In subjects with G551D at least 12years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial. RESULTS: Mean overall sweat chloride value (all patients, all tests, n=1062) was 100.8mmol/L (SD 12.7mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9mmol/L (95% CI 7.4-10.6) and within-subject SD was 8.1mmol/L (95% CI 7.5-8.7). Limits of repeatability for repeat measurements were 19.7 to +21.6mmol/L using values from one arm, and -13.3 to 11.8mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. CONCLUSION: Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter. PMID- 26996269 TI - Extensive cultivation of soil and water samples yields various pathogens in patients with cystic fibrosis but not Burkholderia multivorans. AB - BACKGROUND: While the epidemiology of Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) patients suggests that Burkholderia multivorans is acquired from environmental sources, this species has rarely been isolated from soil and water samples. METHODS: Multiple isolation strategies were applied to water and soil samples that were previously shown to be B. multivorans PCR positive. These included direct plating and liquid enrichment procedures and the use of selective media, acclimatizing recovery and co-cultivation with CF sputum. MALDI-TOF mass spectrometry and sequence analysis of 16S rRNA and housekeeping genes were used to identify all isolates. RESULTS: None of the approaches yielded B. multivorans isolates. Other Burkholderia species, several Gram-negative non fermenting bacteria (including Cupriavidus, Inquilinus, Pandoraea, Pseudomonas and Stenotrophomonas) and rapidly growing mycobacteria (including Mycobacterium chelonae) were all isolated from water and soil samples. CONCLUSIONS: The use of Bcc isolation media yielded a surprisingly wide array of rare but often clinically relevant CF pathogens, confirming that soil and water are reservoirs of these infectious agents. PMID- 26996270 TI - Disease disclosure in individuals with cystic fibrosis: Association with psychosocial and health outcomes. AB - BACKGROUND: This study aimed to quantify cystic fibrosis (CF) disclosure and examine associations between disclosure and psychosocial and health outcomes. METHODS: Participants completed measures assessing disease disclosure and psychosocial outcomes. Data from chart reviews and pharmacy records were obtained. RESULTS: Participants (N=128; ages 16-63) were more likely to disclose to romantic partners (97%) and close friends (94%) than to casual friends (79%), bosses (71%), or co-workers (53%). Participants reported more comfort discussing CF with and doing treatments in front of romantic partners and close friends than other groups. Disclosure was associated with higher social support, social functioning, and medication adherence self-efficacy. Lower lung-function was associated with disclosure to bosses and co-workers. CONCLUSIONS: Clinicians should consider discussing disclosure with patients, as limited disclosure may have a negative impact on psychosocial outcomes. PMID- 26996272 TI - Blood eosinophils and treatment response in hospitalized exacerbations of chronic obstructive pulmonary disease: A case-control study. AB - BACKGROUND: In outpatients with chronic obstructive pulmonary disease (COPD), blood eosinophilia is considered as a biomarker of response to systemic corticosteroid therapy. However, little is known on whether blood eosinophilia is also predictive of positive clinical outcome in severe acute exacerbations of COPD requiring hospitalization. We hypothesized that blood eosinophil-positive severe acute exacerbations of COPD differ from eosinophil-negative ones in terms of response to therapy and clinical outcomes. METHODS: To test our experimental hypothesis, we retrospectively analyzed medical records of patients with COPD admitted to our ward because of severe exacerbation, over a two-year period of observation. After evaluation of inclusion and exclusion criteria, 132 patients were selected and divided in cases (blood eosinophilia >=2% at admission; n = 20) and controls (blood eosinophilia <2% at admission; n = 112). RESULTS: Cases had a shorter hospital stay than controls (geometric mean = 8.9 +/- 1.5 versus 11.3 +/- 1.5 days; p = 0.028). In addition, cases had a significantly lower consumption of systemic corticosteroids (geometric mean = 19.2 +/- 4.0 versus 35.7 +/- 2.5 mg per day of hospitalization; p = 0.012). CONCLUSIONS: In severe acute exacerbations of COPD requiring hospitalization, blood eosinophilia identifies a subgroup of subjects characterized by a prompt response to treatment with shorter hospital stay. PMID- 26996273 TI - Is balloon kyphoplasty safe and effective for cancer-related vertebral compression fractures with posterior vertebral body wall defects? AB - BACKGROUND AND OBJECTIVES: Balloon kyphoplasty (BKP) is a percutaneous treatment for cancer-related vertebral compression fractures (VCF). Posterior vertebral body wall (PVBW) involvement is considered a contraindication for BKP. This study assesses whether BKP is safe and effective for cancer-related VCFs involving the PVBW. METHODS: This study analyzed data on 158 patients with 228 cancer-related VCFs who underwent BKP. One hundred and twelve patients had VCFs with PVBW defects, and 46 had VCFs with no PVBW defect. Outcomes were assessed preoperatively and at 3 months. RESULTS: In the PVBW defect group, mean pain score decreased from 7.5 to 3.6 (P < 0.001), EQ5D increased from 0.39 to 0.48 and Oswestry Disability Index (ODI) decreased from 50 to 42. Cement leaks occurred in 31%. In the PVBW intact group, mean pain decreased from 7.3 to 3.3 (P < 0.001), EQ5D increased from 0.35 to 0.48 (P < 0.001), and ODI decreased from 53 to 50. Cement leaks occurred in 20%. No significant difference was observed in functional improvements between groups. Radiographically kyphotic angle and anterior and middle vertebral body heights were significantly worse in the PVBW defect group (P < 0.05). CONCLUSIONS: BKP can alleviate pain and improve QoL and function in patients with cancer-related VCFs with PVBW defects with no appreciable increase in risk. J. Surg. Oncol. 2016;113:835-842. (c) 2016 Wiley Periodicals, Inc. PMID- 26996275 TI - Effects of sheltering on physiology, immune function, behavior, and the welfare of dogs. AB - Approximately 4 million dogs live in animal shelters each year. However, understanding and measuring the welfare of these kenneled dogs presents a challenge. One way to determine welfare is by assessing how stay at the shelter influences physiology, immune function, and behavior of the dogs. Prior research, from all of these domains, has not resulted in clear conclusions on how the animal shelter influences the well-being of dogs. One robust finding is that, when placed into a kennel environment, dogs experience a spike in cortisol levels followed by a decrease to original at-home levels. Current evidence cannot differentiate between several proposed hypotheses that may be responsible for this pattern. In addition, very few studies have assessed the effects of kenneling on immune function of dogs, and of these, no consistent findings have emerged. However, this line of inquiry can have a large impact as infectious diseases are rampant in animal shelters. The ability of behavioral measures to inform us about the welfare of dogs is discussed by reviewing published and new data on the effects of kenneling on dog behavior. Prior research has suffered from a lack of consistent operational definitions when defining abnormal behavior in dogs, resulting in difficult to interpret results. Research on the well-being of individual dogs, rather than on group averages, may be a fruitful next step in determining and improving the welfare of dogs housed in shelters. PMID- 26996274 TI - Worry processes in patients with persecutory delusions. AB - OBJECTIVES: Worry may be common in patients with paranoia and a contributory causal factor in the occurrence of the delusions. A number of psychological mechanisms have been linked to the occurrence of worry in emotional disorders but these are yet to be investigated in psychosis. The primary aim of the study was to test the links between five main worry mechanisms - perseverative thinking, catastrophizing, stop rules, metacognitive beliefs, and intolerance of uncertainty - and the cognitive style of worry in patients with persecutory delusions. METHOD: One hundred and fifty patients with persecutory delusions completed assessments of paranoia, worry, and worry mechanisms. RESULTS: Worry in patients with psychosis was associated with the following: a perseverative thinking style, an 'as many as can' stop rule, a range of metacognitive beliefs (cognitive confidence, worry as uncontrollable and the need to control thoughts), and intolerance of uncertainty. Higher levels of worry were associated with higher levels of paranoia. There was also evidence that intolerance of uncertainty and the metacognitive belief concerning the need to control thoughts were independently associated with paranoia. CONCLUSIONS: Worry in patients with persecutory delusions may well be understood by similar underlying mechanisms as worry in emotional disorders. This supports the use of interventions targeting worry, suitably modified, for patients with psychosis. PRACTITIONER POINTS: Worry is a significant concern for patients with paranoia Worry in paranoia is likely to be caused by similar mechanisms as worry in emotional disorders The results support the recent trial findings that standard techniques for treating worry in anxiety, suitably modified, are applicable for patients with paranoia LIMITATIONS: The findings are limited by the self-report nature of measures and by the study design which precludes any assumptions about the direction of causality between the psychological mechanisms and worry. PMID- 26996276 TI - How good is this food? A study on dogs' emotional responses to a potentially pleasant event using infrared thermography. AB - Understanding how animals express positive emotions is becoming an interesting and promising area of research in the study of animal emotions and affective experiences. In the present study, we used infrared thermography in combination with behavioral measures, heart rate (HR) and heart rate variability (HRV), to investigate dogs' emotional responses to a potentially pleasant event: receiving palatable food from the owner. Nineteen adult pet dogs, 8 females and 11 males, were tested and their eye temperature, HR, HRV and behavior were recorded during a 30-minutestestconsisting of three 10-minute consecutive phases: Baseline (Phase 1), positive stimulation through the administration of palatable treats (Feeding, Phase 2) and Post-feeding condition following the positive stimulation (Phase 3). Dogs' eye temperature and mean HR significantly increased during the positive stimulation phase compared with both Baseline and Post-feeding phases. During the positive stimulation with food (Phase 2), dogs engaged in behaviors indicating a positive emotional state and a high arousal, being focused on food treats and increasing tail wagging. However, there was no evidence of an increase in HRV during Phase 2 compared to the Phase 1, with SDNN significantly increasing only in Phase 3, after the positive stimulation occurred. Overall results point out that IRT may be a useful tool in assessing emotional states in dogs in terms of arousal but fails to discriminate emotional valence, whose interpretation cannot disregard behavioral indexes. PMID- 26996277 TI - Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer. AB - Regulated intramembrane proteolysis (RIP) has been shown to be an important mechanism for oncogenic activation of EpCAM through nuclear translocation of the intracellular domain EpICD. Recently, we identified two different membranous EpCAM variants namely EpCAM(MF) (full-length) and EpCAM(MT) (truncated) to be expressed in the majority of human epithelial tumors. The aim of our study was to evaluate the potential role of these two protein variants as additional prognostic biomarkers in colorectal cancer. In most studies only one antibody targeting the extracellular domain of EpCAM (EpEX) has been used, whereas in the present study additionally an antibody which detects the intracellular domain (EpICD) was applied to discriminate between different EpCAM variants. Using immunohistochemistry, we analyzed the expression of EpCAM(MF) and EpCAM(MT) variants in 640 patients with colorectal cancer and determined their correlations with other prognostic factors and clinical outcome. A statistically significant association was observed for EpCAM(MT) with advanced tumor stage (p < 0.001), histological grade (p = 0.01), vascular (p < 0.001) and marginal (p = 0.002) invasion. Survival analysis demonstrated reduced overall survival (p < 0.004) in patients with tumors expressing the EpCAM(MT) phenotype when compared to patients with tumors expressing the EpCAM(MF) variant. In conclusion, this study for the first time indicates that expression of EpCAM(MT) is associated with a more aggressive phenotype and predicts poor survival in patients with colorectal cancer. PMID- 26996278 TI - Pancreas volume and fat fraction in children with Type 1 diabetes. AB - AIMS: People with Type 1 diabetes have smaller pancreases than healthy individuals. Several diseases causing pancreatic atrophy are associated with pancreatic steatosis, but pancreatic fat in Type 1 diabetes has not been measured. This cross-sectional study aimed to compare pancreas size and fat fraction in children with Type 1 diabetes and controls. METHODS: The volume and fat fraction of the pancreases of 22 children with Type 1 diabetes and 29 controls were determined using magnetic resonance imaging. RESULTS: Pancreas volume was 27% smaller in children with diabetes (median 34.9 cm(3) ) than in controls (47.8 cm(3) ; P < 0.001). Pancreas volume correlated positively with age in controls (P = 0.033), but not in children with diabetes (P = 0.649). Pancreas volume did not correlate with diabetes duration, but it did correlate positively with units of insulin/kg body weight/day (P = 0.048). A linear model of pancreas volume as influenced by age, body surface area and insulin units/kg body weight/day found that insulin dosage correlated with pancreas volume after controlling for both age and body surface area (P = 0.009). Pancreatic fat fraction was not significantly different between the two groups (1.34% vs. 1.57%; P = 0.891). CONCLUSIONS: Our findings do not indicate that pancreatic atrophy in Type 1 diabetes is associated with an increased pancreatic fat fraction, unlike some other diseases featuring reduced pancreatic volume. We speculate that our results may support the hypotheses that much of pancreatic atrophy in Type 1 diabetes occurs before the clinical onset of the disease and that exogenous insulin administration decelerates pancreatic atrophy after diabetes onset. PMID- 26996279 TI - Incremental cost of implementing residual insecticide treatment with delthametrine on top of intensive routine Aedes aegypti control. AB - OBJECTIVE: Information on the cost of implementing residual insecticide treatment (RIT) for Aedes control is scarce. We evaluated the incremental cost on top of intensive conventional routine activities of the Aedes control programme (ACP) in the city of Santiago de Cuba, Cuba. METHODS: We conducted the cost analysis study in 2011-2012, from the perspective of the ACP. Data sources were bookkeeping records, activity registers of the Provincial ACP Centre and the accounts of an RIT implementation study in 21 clusters of on average four house blocks comprising 5180 premises. RESULTS: The annual cost of the routine ACP activities was 19.66 US$ per household. RIT applications in rounds at 4-month intervals covering, on average, 97.2% and using 8.5 g of delthametrine annually per household, cost 3.06 US$ per household per year. Delthametrine comprised 66.5% of this cost; the additional cost for deploying RIT comprised 15.6% of the total ACP routine cost and 27% of the cost related to routine adult stage Aedes control. CONCLUSIONS: The incremental cost of implementing RIT is high. It should be weighed against the incremental effect on the burden caused by the array of pathogens transmitted by Aedes. The cost could be reduced if the insecticide became cheaper, by limiting the number of yearly applications or by targeting transmission hot spots. PMID- 26996280 TI - Molecularly proven mosaicism in phenotypically normal parent of a girl with Freeman-Sheldon Syndrome caused by a pathogenic MYH3 mutation. AB - We report a case of a female child who has classical Freeman-Sheldon syndrome (FSS) associated with a previously reported recurrent pathogenic heterozygous missense mutation, c.2015G > A, p. (Arg672His), in MYH3 where the phenotypically normal mother is a molecularly confirmed mosaic. To the best of our knowledge, this is the first report in the medical literature of molecularly confirmed parental mosaicism for a MYH3 mutation causing FSS. Since proven somatic mosaicism after having an affected child is consistent with gonadal mosaicism, a significantly increased recurrence risk is advised. Parental testing is thus essential for accurate risk assessment for future pregnancies and the use of new technologies with next generation sequencing (NGS) may improve the detection rate of mosaicism. (c) 2016 Wiley Periodicals, Inc. PMID- 26996281 TI - Development of Diubiquitin-Based FRET Probes To Quantify Ubiquitin Linkage Specificity of Deubiquitinating Enzymes. AB - Deubiquitinating enzymes (DUBs) are proteases that fulfill crucial roles in the ubiquitin (Ub) system, by deconjugation of Ub from its targets and disassembly of polyUb chains. The specificity of a DUB towards one of the polyUb chain linkages largely determines the ultimate signaling function. We present a novel set of diubiquitin FRET probes, comprising all seven isopeptide linkages, for the absolute quantification of chain cleavage specificity of DUBs by means of Michaelis-Menten kinetics. Each probe is equipped with a FRET pair consisting of Rhodamine110 and tetramethylrhodamine to allow the fully synthetic preparation of the probes by SPPS and NCL. Our synthetic strategy includes the introduction of N,N'-Boc-protected 5-carboxyrhodamine as a convenient building block in peptide chemistry. We demonstrate the value of our probes by quantifying the linkage specificities of a panel of nine DUBs in a high-throughput manner. PMID- 26996283 TI - Social integration and substance use: assessing the effects of an early intervention programme for youth. AB - AIM: Appropriate social integration has been shown to be a protective factor against substance use among adolescents and associated negative consequences. Promoting social integration through early intervention with adolescents using substances is thus necessary and is the aim of the Identification, Assessment and Follow-up of Adolescents with Substance Use (in French, Depistage - evaluation - parrainage d'adolescents consommateurs de substances (DEPART) programme. The present study aimed to describe this programme and its participants from 2009 to 2013 as well as to assess its effects on social integration. METHODS: Data from 398 adolescents using substances who attended the DEPART programme were analysed. RESULTS: The results showed that almost 80% of the adolescents admitted to the DEPART programme were boys, with a large proportion using cannabis. Globally, social integration did not increase from admission to discharge from the programme, but a shift was observed for school and professional integration. Additionally, after the intervention, we observed that social integration was more important in younger patients. CONCLUSIONS: This study showed that adolescents with problematic substance use mostly consumed soft drugs and that those who were integrated into the DEPART programme at a younger age were more likely to be socially integrated at the end of the programme. PMID- 26996282 TI - A review of perioperative anaphylaxis at a Singapore tertiary hospital. AB - INTRODUCTION: Perioperative anaphylaxis is an anaesthetic emergency, but its incidence is not well described in the local literature. This retrospective study aims to look at a group of patients who had perioperative anaphylaxis in our institution. METHODS: We conducted a retrospective review of electronic databases and clinical case sheets, and identified 34 patients who had possible perioperative anaphylaxis during anaesthesia in our institution between 1 January 2007 and 30 April 2012. RESULTS: After reviewing clinical and biochemical data, we found that 16 out of 151,876 patients who underwent surgery had confirmed perioperative anaphylaxis, an incidence of 1:10,000. Neuromuscular blockers were identified as the most common causative agent for perioperative anaphylaxis. The offending agent could not be identified in seven patients. CONCLUSION: To the best of our knowledge, this is the first study in Southeast Asia on the incidence of perioperative anaphylaxis. Having a preoperative history of allergy did not seem to predispose patients to the subsequent development of perioperative anaphylaxis. PMID- 26996284 TI - A light-activated amnion wrap strengthens colonic anastomosis and reduces peri anastomotic adhesions. AB - BACKGROUND AND OBJECTIVE: Colonic anastomotic failure is a dreaded complication, and multiple surgical techniques have failed to eliminate it. Photochemical tissue bonding (PTB) is a method of sealing tissue surfaces by light-activated crosslinking. We evaluated if a human amniotic membrane (HAM), sealed over the anastomotic line by PTB, increases the anastomotic strength. STUDY DESIGN: Sprague-Dawley rats underwent midline laparotomy followed by surgical transection of the left colon. Animals were randomized to colonic anastomosis by one of the following methods (20 per group): single-layer continuous circumferential suture repair (SR); SR with a HAM wrap attached by suture (SR+ HAM-S); SR with HAM bonded photochemically over the anastomotic site using 532 nm light (SR+ HAM PTB); approximation of the bowel ends with only three sutures and sealing with HAM-PTB (3+ HAM-PTB). A control group underwent laparotomy alone with no colon resection (NR). Sub-groups (n = 10) were sacrificed at days 3 and 7 post operatively and adhesions were evaluated. A 6 cm section of colon was then removed and strength of anastomosis evaluated by burst pressure (BP) measurement. RESULTS: A fourfold increase in BP was observed in the SR+ HAM-PTB group compared to suture repair alone (94 +/- 3 vs. 25 +/- 8 mm Hg, P < 0.0001) at day 3. At day 7 the burst pressures were 165 +/- 40 and 145 +/- 31 mm Hg (P = 1), respectively. A significant decrease in peri-anastomotic adhesions was observed in the SR+ HAM PTB group compared to the SR group at both time points (P < 0.001). CONCLUSION: Sealing sutured colonic anastomotic lines with HAM-PTB increases the early strength of the repair and reduces peri-anastomotic adhesions. Lasers Surg. Med. 48:530-537, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26996286 TI - Reporting real-life experience with drugs in lymphoma patients. PMID- 26996285 TI - Obesity and trauma mortality: Sizing up the risks in motor vehicle crashes. AB - BACKGROUND: Protective effects of safety devices in obese motorists in motor vehicle collisions (MVC) remain unclear. Aim of our study is to assess the association between morbid obesity and mortality in MVC, and to determine the efficacy of protective devices. We hypothesised that patients with morbid obesity will be at greater risk of death after MVC. METHODS: A retrospective analysis of MVC patients (age >=16 y.o.) was performed using the National Trauma Data Bank from 2007 to 2010. Patients with recorded comorbidity of morbid obesity (BMI>=40) were identified. Patients dead on arrival, with isolated traumatic brain injury, or incomplete data were excluded. The primary outcome was in-hospital mortality. Multivariate logistic regression was performed. RESULTS: Our sample of 214,306 MVC occupants included 10,260 (4.8%) morbidly obese patients. Mortality risk was greatest among occupants with morbid obesity (ORcrude 1.74 [1.54-1.98]). After adjusting for patient demographics, safety device and physiological severity, odds of death was 1.52 [1.33-1.74] times greater in motorists with morbid obesity. Motorists with morbid obesity were at greater risk of death if no restraint (OR 1.84 [1.47-2.31]), seatbelt only (OR 1.48 [1.17-1.86]), or both seatbelt and airbag were present (OR 1.49 [1.13-1.97]). No significant differences in the odds of death exist between drivers with morbid obesity and non-morbidly obese drivers with only airbag deployment (OR 0.99 [0.65-1.51]). CONCLUSIONS: Motorists with morbid obesity are at greater risk of MVC. Regardless of safety device use, occupants with morbid obesity remained at greater risk of death. Further research examining the effectiveness of vehicle restraints in drivers with morbid obesity is warranted. PMID- 26996287 TI - Characterization of the Migration of Hop Volatiles into Different Crown Cork Liner Polymers and Can Coatings. AB - Absorption of hop volatiles by crown cork liner polymers and can coatings was investigated in beer during storage. All hop volatiles measured were prone to migrate into the closures, and the absorption kinetics was demonstrated to fit Fick's second law of diffusion well for a plane sheet. The extent and rate of diffusion were significantly dissimilar and were greatly dependent upon the nature of the volatile. Diffusion coefficients ranged from 1.32 * 10(-5) cm(2)/day (limonene) to 0.26 * 10(-5) cm(2)/day (alpha-humulene). The maximum amounts absorbed into the material at equilibrium were in the following order: limonene > alpha-humulene > trans-caryophyllene > myrcene ? linalool > alpha terpineol > geraniol. With the application of low-density polyethylene (LDPE) liners with oxygen-scavenging functionality, oxygen-barrier liners made up from high-density polyethylene (HDPE) or liner polymers from a different manufacturer had no significant effect on the composition of hop volatiles in beers after prolonged storage of 55 days; however, significantly higher amounts of myrcene and limonene were found in the oxygen-barrier-type crown cork, while all other closures behaved similarly. Can coatings were demonstrated to absorb hop volatiles in a similar pattern as crown corks but to a lesser extent. Consequently, significantly higher percentages of myrcene were found in the beers. PMID- 26996288 TI - Relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents - a report from the United Kingdom's Children's Cancer and Leukaemia Study Group. AB - There is a paucity of data on the treatment outcome in children with relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma (nLPHL). This retrospective report evaluates the treatment outcome in a national cohort of children with relapsed or poorly responsive nLPHL. A total of 37 patients, 22 with relapsed and 15 with poorly responding disease, are the subjects of this report. Of the 22 patients with relapsed nLPHL, 11 had relapsed after primary excision biopsy, 10 after chemotherapy and 1 after chemotherapy and involved field radiotherapy. The majority had localized disease at relapse. The median time to relapse was 8 months after chemotherapy and 11 months after excision biopsy. Seven of the 15 patients with poorly responding nLPHL had variant histology. Three patients with initial poor response did not receive any further treatment and have had no disease progression. Transformation to diffuse large B cell lymphoma, in addition to evolution from typical to variant nLPHL occurred in one patient each. Thirty-four patients have been successfully re-treated with second chemotherapy or radiotherapy. Multiple relapses were uncommon but treatable. Relapse or poorly responsive nLPHL is fully salvageable with either additional chemotherapy and or radiotherapy. PMID- 26996289 TI - ERCP development in the largest developing country: a national survey from China in 2013. AB - BACKGROUND AND AIMS: The ERCP volume in developed countries has decreased recently, whereas the ERCP trend is unknown in developing countries. This study aimed to evaluate the ERCP development in China between 2006 and 2012. METHODS: All hospitals performing ERCP in mainland China in 2012 participated in an online survey. Data on ERCP infrastructure, volume, indication, and adverse events were collected and compared with those in a previous national survey and in developed countries. RESULTS: From 2006 to 2012 the number of hospitals performing ERCP in China increased from 470 to 1156. The total ERCP volume increased from 63,787 to 195,643, of which >95% were therapeutic. The ERCP rate in China (14.4 per 100,000 inhabitants) in 2012 was still much lower than that in developed countries. There was significant imbalance between different regions (1.3-99.1 per 100,000 inhabitants). The median ERCP volume per hospital decreased from 80 (interquartile range [IQR], 31-150) in 2006 to 52 (IQR, 20-146) in 2012. The median volume of the 686 hospitals that started ERCP after 2006 was 31.5 (IQR, 11 82). The post-ERCP adverse event rate in 2012 was comparable between hospitals in terms of volume (>=500 or <500 per year: 5.8% vs 5.6%) and practice durations (starting ERCP before or after 2006: 5.5% vs 5.6%). CONCLUSIONS: ERCP has developed considerably in China in recent years. Despite low annual volume, the hospitals starting ERCP after 2006 have acceptable adverse event rates and will be promising and important sources of ERCP development in China. PMID- 26996290 TI - Incidence and impact of scheduled endoscopic surveillance on recurrence after curative endoscopic resection for early gastric cancer. AB - BACKGROUND AND AIMS: The aim of this study was to identify the incidence of recurrent lesions after endoscopic submucosal dissection (ESD) and to determine whether scheduled endoscopic surveillance might control their development and treatment. METHODS: We reviewed the clinical data of patients who underwent gastric ESD between March 2007 and April 2014. RESULTS: A total of 1347 patients who underwent curative ESD for early gastric cancer that met the expanded indication for ESD were analyzed. Of these, recurrence at the previous ESD site occurred in 39 patients, whereas recurrence in the stomach at a site other than the ESD site occurred in 102 patients. Older age, intestinal metaplasia, flat or depressed lesions, and ESD criteria were associated with recurrence in the stomach in places other than the ESD site. The annual incidence was .84% for recurrence at the previous ESD site and 2.48% for recurrence in the stomach at other than the ESD site. In cases of local recurrence and metachronous lesions, there was a significant difference between the short- and long-surveillance interval group (<=12 months vs >12 months) in the proportions of recurrent adenocarcinoma (31.9% vs 60.9%, P = .021), additional gastrectomy (7.1% vs 46.2%, P = .033), and size (8.92 +/- 4.17 mm vs 18.08 +/- 10.47 mm, P = .010). CONCLUSIONS: Scheduled endoscopy surveillance is necessary for detecting recurrent lesions. In addition, scheduled endoscopy surveillance might help to detect recurrent lesions at a stage early enough for a curative resection. PMID- 26996291 TI - Two-year effects and cost-effectiveness of pelvic floor muscle training in mild pelvic organ prolapse: a randomised controlled trial in primary care. AB - OBJECTIVE: To compare effects and cost-effectiveness of pelvic floor muscle training (PFMT) and watchful waiting in women with pelvic organ prolapse. DESIGN: Randomised controlled trial. SETTING: Dutch general practice. POPULATION: Women (>=55 years) with symptomatic mild prolapse, identified by screening. METHODS: Linear multilevel analysis. MAIN OUTCOME MEASURES: Primary outcome was change of pelvic floor symptoms (Pelvic-Floor-Distress-Inventory-20 [PFDI-20]) during 24 months. Secondary outcomes were condition-specific and general quality of life, costs, sexual functioning, prolapse stage, pelvic floor muscle function and women's perceived improvement of symptoms. RESULTS: PFMT (n = 145) resulted in a 12.2-point (95% CI 7.2-17.2, P < 0.001) greater improvement in PFDI-20 score during 24 months compared with watchful waiting (n = 142). Participants randomised to PFMT more often reported improved symptoms (43% versus 14% for watchful waiting). Direct medical costs per person were ?330 for PFMT and ?91 for watchful waiting but costs for absorbent pads were lower in the PFMT group (?40 versus ?77). Other secondary outcomes did not differ between groups. Post-hoc subgroup analysis demonstrated that PFMT was more effective in women experiencing higher pelvic floor symptom distress at baseline. CONCLUSION: PFMT resulted in greater pelvic floor symptom improvement compared with watchful waiting. The difference was statistically significant, but below the presumed level of clinical relevance (15 points). PFMT more often led to women's perceived improvement of symptoms, lower absorbent pads costs, and was more effective in women experiencing higher pelvic floor symptom distress. Therefore, PFMT could be advised in women with bothersome symptoms of mild prolapse. TWEETABLE ABSTRACT: Pelvic floor muscle training can be effective in women with bothersome symptoms of mild prolapse. PMID- 26996293 TI - Selective cytotoxicity and modulation of apoptotic signature of breast cancer cells by Pithecellobium dulce leaf extracts. AB - We report the potent and selective cytotoxicity of the crude aqueous leaf extract from the medicinal plant, Pithecellobium dulce toward the human breast cancer cells (MCF-7), but not the normal cells (MCF-10A). The cytotoxicity was found to be dose and time dependent, as 300 ug/mL of the extract decreased the cell viability to 50% (IC50 ) in 48 h. The induction of apoptosis in the breast cancer cells after treatment was confirmed by significant percentage (24.7%), of early apoptotic cells (AnnexinV (+) Propidium Iodide(_) ) in treated cells as compared to control cells (3.5%). We observed a significant upregulation in the mRNA expression of various pro-apoptotic gene such as Bax (21.1 folds), p21(14.4 folds), p53 (11.7 folds), TNF (10.2 folds) and fas (6.3 folds) after treatment as compared to untreated cells. On the other hand, the relative mRNA expression of anti-apoptotic genes such as Bcl-2, NF-KB and Cdk was reduced. The selective upregulation of pro-apoptotic gene and down regulation of specific anti-apoptotic genes could be the inducing factor for apoptotic cell death in MCF-7 cells after treatment with the herbal extract. We believe that our findings provide a foundation for further studies on this formulation as a potential therapeutic candidate for breast cancer. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:756-766, 2016. PMID- 26996292 TI - Four-dimensional live imaging of hemodynamics in mammalian embryonic heart with Doppler optical coherence tomography. AB - Hemodynamic analysis of the mouse embryonic heart is essential for understanding the functional aspects of early cardiogenesis and advancing the research in congenital heart defects. However, high-resolution imaging of cardiac hemodynamics in mammalian models remains challenging, primarily due to the dynamic nature and deep location of the embryonic heart. Here we report four dimensional micro-scale imaging of blood flow in the early mouse embryonic heart, enabling time-resolved measurement and analysis of flow velocity throughout the heart tube. Our method uses Doppler optical coherence tomography in live mouse embryo culture, and employs a post-processing synchronization approach to reconstruct three-dimensional data over time at a 100 Hz volume rate. Experiments were performed on live mouse embryos at embryonic day 9.0. Our results show blood flow dynamics inside the beating heart, with the capability for quantitative flow velocity assessment in the primitive atrium, atrioventricular and bulboventricular regions, and bulbus cordis. Combined cardiodynamic and hemodynamic analysis indicates this functional imaging method can be utilized to further investigate the mechanical relationship between blood flow dynamics and cardiac wall movement, bringing new possibilities to study biomechanics in early mammalian cardiogenesis. Four-dimensional live hemodynamic imaging of the mouse embryonic heart at embryonic day 9.0 using Doppler optical coherence tomography, showing directional blood flows in the sinus venosus, primitive atrium, atrioventricular region and vitelline vein. PMID- 26996294 TI - Poly(l-Lactic Acid)/Gelatin Fibrous Scaffold Loaded with Simvastatin/Beta Cyclodextrin-Modified Hydroxyapatite Inclusion Complex for Bone Tissue Regeneration. AB - Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l-lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and beta-cyclodextrin (betaCD) grafted nano-hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between betaCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining betaCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp-(betaCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering. PMID- 26996295 TI - Recent Advances in Inorganic Heterogeneous Electrocatalysts for Reduction of Carbon Dioxide. AB - In view of the climate changes caused by the continuously rising levels of atmospheric CO2 , advanced technologies associated with CO2 conversion are highly desirable. In recent decades, electrochemical reduction of CO2 has been extensively studied since it can reduce CO2 to value-added chemicals and fuels. Considering the sluggish reaction kinetics of the CO2 molecule, efficient and robust electrocatalysts are required to promote this conversion reaction. Here, recent progress and opportunities in inorganic heterogeneous electrocatalysts for CO2 reduction are discussed, from the viewpoint of both experimental and computational aspects. Based on elemental composition, the inorganic catalysts presented here are classified into four groups: metals, transition-metal oxides, transition-metal chalcogenides, and carbon-based materials. However, despite encouraging accomplishments made in this area, substantial advances in CO2 electrolysis are still needed to meet the criteria for practical applications. Therefore, in the last part, several promising strategies, including surface engineering, chemical modification, nanostructured catalysts, and composite materials, are proposed to facilitate the future development of CO2 electroreduction. PMID- 26996296 TI - (64)Cu-ATSM therapy targets regions with activated DNA repair and enrichment of CD133(+) cells in an HT-29 tumor model: Sensitization with a nucleic acid antimetabolite. AB - (64)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) is a potential theranostic agent targeting the over-reduced state under hypoxia within tumors. Recent clinical Cu-ATSM positron emission tomography studies have revealed a correlation between uptake and poor prognosis; however, the reason is unclear. Here, using a human colon carcinoma HT-29 model, we demonstrated that the intratumoral (64)Cu-ATSM high-uptake regions exhibited malignant characteristics, such as upregulated DNA repair and elevated %CD133(+) cancer stem-like cells. Based on this evidence, we developed a strategy to enhance the efficacy of (64)Cu ATSM internal radiotherapy (IRT) by inhibiting DNA repair with a nucleic acid (NA) antimetabolite. The results of the analyses showed upregulation of pathways related to DNA repair along with NA incorporation (bromodeoxyuridine uptake) and elevation of %CD133(+) cells in (64)Cu-ATSM high-uptake regions. In an in vivo(64)Cu-ATSM treatment study, co-administration of an NA antimetabolite and (64)Cu-ATSM synergistically inhibited tumor growth, with little toxicity, and effectively reduced %CD133(+) cells. (64)Cu-ATSM therapy targeted malignant tumor regions with activated DNA repair and high concentrations of CD133(+) cells in the HT-29 model. NA antimetabolite co-administration can be an effective approach to enhance the therapeutic effect of (64)Cu-ATSM IRT. PMID- 26996297 TI - AhR ligand Aminoflavone inhibits alpha6-integrin expression and breast cancer sphere-initiating capacity. AB - Traditional chemotherapies debulk tumors but fail to produce long-term clinical remissions due to their inability to eradicate tumor-initiating cells (TICs). This necessitates therapy with activity against the TIC niche. Alphalpha6 integrin (alpha6-integrin) promotes TIC growth. In contrast, aryl hydrocarbon receptor (AhR) signaling activation impedes the formation of mammospheres (clusters of cells enriched for TICs). We investigated the ability of AhR agonist Aminoflavone (AF) and AF pro-drug (AFP464) to disrupt mammospheres derived from breast cancer cells and a M05 mammary mouse model of breast cancer respectively. We further examined the capacity of AF and AFP464 to exhibit anticancer activity and modulate the expression of 'stemness' genes including alpha6-integrin using immunofluorescence, flow cytometry and qRT-PCR analysis. AF disrupted mammospheres and prevented secondary mammosphere formation. In contrast, AF did not disrupt mammospheres derived from AhR ligand-unresponsive MCF-7 cells. AFP464 treatment suppressed M05 tumor growth and disrupted corresponding mammospheres. AF and AFP464 reduced the expression and percentage of cells that stained for 'stemness' markers including alpha6-integrin in vitro and in vivo respectively. These data suggest AFP464 thwarts bulk breast tumor and TIC growth via AhR agonist-mediated alpha6-integrin inhibition. PMID- 26996298 TI - Leptin contributes to long-term stabilization of HIF-1alpha in cancer cells subjected to oxygen limiting conditions. AB - Leptin, a cytokine produced by the adipose tissue in response to food intake, is a key player in the regulation of energy balance and body weight control. Physiological action of leptin in modulating the metabolic adaptation of different peripheral tissues supports the hypothesis that it could also exert a direct effect on cancer cells. In vitro, treatment with leptin up-regulated HIF 1alpha and stimulated adhesion and invasion of prostate cancer cells cultured in hypoxia. Leptin action was effective in both low and high glycolytic cancer cell lines, and determined the up-regulation of lactate exporter MCT4 and its associated protein CD147. HIF-1alpha stabilization was oligomycin-independent and was associated with an important modulation of mitochondrial homeostasis. In fact, leptin treatment produced mitochondrial biogenesis, stabilization of mitochondrial membrane potential and increased uncoupled respiration through the up-regulation of UCP2. Furthermore, leptin counteracted the downmodulation of SIRT1 induced by hypoxia, and persistent high levels of SIRT1 were directly involved in HIF-1alpha stabilization. Leptin can sustain cancer progression in hypoxic environment and when mitochondrial respiration is impaired. Leptin signaling axis, including the new proposed intermediate SIRT1, could represent a new diagnostic and therapeutic target in prostate cancer. PMID- 26996299 TI - An integrin beta4-EGFR unit promotes hepatocellular carcinoma lung metastases by enhancing anchorage independence through activation of FAK-AKT pathway. AB - Anoikis, a form of programmed cell death, occurs when the cells are detached from the appropriate extracellular matrix. Anoikis resistance or anchorage independence is necessary for distant metastases of cancer. The mechanisms by which hepatocellular carcinoma (HCC) cells become resistant to anoikis are not fully understood. Integrin beta4 (ITGB4, also known as CD104) is associated with progression of many human cancers. In this study, we demonstrate that ITGB4 is over-expressed in HCC tissues and aggressive HCC cell lines. To explore the role of ITGB4 in HCC, we inhibited its expression using small interfering RNA in two HCC cell lines: HCCLM3 and HLF. We show that knockdown of ITGB4 significantly enhanced susceptibility to anoikis through inhibition of AKT/PKB signaling. Moreover, ITGB4 interacts with epidermal growth factor receptor (EGFR) in a ligand independent manner. Inactivation of EGFR inhibits the anchorage independence and AKT pathway promoted by ITGB4. Further investigation proved that the ITGB4-EGFR unit triggers the focal adhesion kinase (FAK) to activate the AKT signaling pathway. Finally, we demonstrate that over-expression of ITGB4 is positively associated with tumor growth and lung metastases of HCC in vivo. Collectively, we demonstrate for the first time that ITGB4 is overexpressed in HCC tissues and promotes metastases of HCC by conferring anchorage independence through EGFR-dependent FAK-AKT activation. PMID- 26996300 TI - RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1alpha mRNA is translated. AB - YTH domain containing 2 (YTHDC2) is a member of the DExD/H-box family of ATP dependent RNA helicases. We previously found that YTHDC2 expression is up regulated in several human cancer cells. In this study, we demonstrate novel roles for YTHDC2 in metastasis of colon tumor cells via translation-dependent pathway. Knockdown of YTHDC2 attenuated protein expression of metastasis-related genes, such as hypoxia-inducible factor-1alpha (HIF-1alpha), and inhibited metastasis of colon tumor cells in vitro and in vivo. To confirm that YTHDC2 promotes translation initiation by unwinding the 5'-untranslated region (5'UTR) of mRNA, we constructed a firefly luciferase reporter containing the 5'UTR of the HIF-1alpha mRNA and showed reduction in luciferase activity in YTHDC2-silenced cells. Furthermore, we examined expression levels of YTHDC2 by immunohistochemical staining in human colon cancer tissues from 72 patients and found a significantly positive correlation between YTHDC2 expression and the tumor stage, including metastasis. In conclusion, these results suggest that the RNA helicase YTHDC2 contributes to colon tumor metastasis by promoting translation of HIF-1alpha and that YTHDC2 is potentially a diagnostic marker and target gene for treating colon cancer patients. PMID- 26996301 TI - Mesenchymal stem cells generate pericytes to promote tumor recurrence via vasculogenesis after stereotactic body radiation therapy. AB - BACKGROUND: Stereotactic body radiation therapy (SBRT) is postulated to enhance the recruitment of mesenchymal stem cells (MSCs) into the tumor microenvironment, which promote tumor recurrence. The aim of this study is to determine the molecular mechanisms behind SBRT stimulating MSC migration and differentiation. METHODS: In vitro, mediated factors and migrated MSCs (post-SBRT) were generated. In vivo, bone-marrow derived MSCs were identified and harvested from green fluorescent protein (GFP)-expressing transgenic male mice and transplanted into sub-lethally irradiated recipient female mice to establish a model of bone marrow transplantation. Lewis lung carcinoma and malignant melanoma-bearing recipient mice were treated with SBRT, 14 Gy/1 fraction. The migration and differentiation potential of MSCs were characterized. RESULTS: SBRT increased the release of stromal cell derived factor-1alpha (SDF-1alpha) and platelet-derived growth factor-B (PDGF-B) by tumor cells; these ligands bound to chemokine (C-X-C motif) receptor 4 (CXCR4) and platelet-derived growth factor receptor-beta (PDGFR-beta), respectively, on circulating bone marrow-derived MSCs, resulting in engraftment of the MSCs into the tumor parenchyma. The newly-homed MSCs differentiated into pericytes, which induced the tumor vasculogenesis, and promoted tumor regrowth. Targeted therapies, AMD3100 and imatinib abrogated MSC homing, vasculogenesis, and tumor regrowth. CONCLUSION: Bone-marrow derived MSCs migrate to the tumor parenchyma and differentiate into pericytes, inducing tumor vasculogenesis after SBRT, and promoting tumor recurrence. MSC migration and maturation may be abrogated with AMD3100 and imatinib. This novel treatment strategy warrants clinical investigation. PMID- 26996302 TI - New potential peptide therapeutics perturbing CK1delta/alpha-tubulin interaction. AB - Members of the CK1 family are highly conserved serine/threonine specific kinases being expressed in all eukaryotes. They are involved in many cellular processes and therefore tightly regulated. A central mechanism to modulate CK1 activity is via interaction with cellular proteins. CK1delta interacts with alpha-/beta tubulin and is involved in the regulation of microtubule dynamics. Therefore, it is important to identify the structural elements responsible for the interaction between these proteins. Using a peptide library covering the human CK1delta amino acid sequence in SPR and ELISA analyses, we identified peptide 39 (P39), encompassing aa361-aa375 of CK1delta, as a prominent binding partner of alpha tubulin. P39 decreases alpha-tubulin phosphorylation by CK1delta and reduces the thermodynamic stability of alpha-tubulin in fluorescence thermal shift assays. Furthermore, P39 induces an inhibition of mitotic progression and a disruption of cells entering mitosis in CV-1 cells. Taken together our data provide valuable information regarding the interaction of CK1delta and alpha-tubulin and a novel approach for the development of pharmacological tools to inhibit proliferation of cancer cells. PMID- 26996303 TI - [What do internists do? Innovative answers to new requirements]. PMID- 26996304 TI - Carbachol dimers as homobivalent modulators of muscarinic receptors. AB - A series of homodimers of the well-known cholinergic agonist carbachol have been synthesized, showing the two agonist units symmetrically connected through a methylene chain of variable length. The new compounds have been tested on the five cloned muscarinic receptors (hM1-5) expressed in CHO cells by means of equilibrium binding studies, showing an increase in affinity by rising the number of methylene units up to 7 and 9. Functional experiments on guinea-pig ileum and assessment of ERK1/2 phosphorylation on hM1, hM2 and hM3 on CHO cells have shown that the new compounds are endowed with muscarinic antagonistic properties. Kinetic binding studies have revealed that some of the tested compounds are able to slow the rate of dissociation of NMS, suggesting a bitopic behavior. Docking simulations, performed on the hM1 and hM2 receptors, give a sound rationalization of the experimental data revealing how these compounds are able to interact with both orthosteric and allosteric binding sites depending on the length of their connecting chain. PMID- 26996305 TI - Anti-NMDAR antibodies in new-onset psychosis. Positive results in an HIV-infected patient. AB - The role of neuronal surface autoantibodies (NSAs) in non-encephalitic psychosis is of recent and controversial interest. Most of the studies relating NSAs with psychosis are retrospective and only focused on the N-methyl-d-aspartate glutamate receptor (NMDAR). Our goal was to evaluate the prevalence of IgG antibodies against the NMDAR NR1 subunit (NMDAR-Abs) along with five additional NSAs in 61 first psychotic episode patients and 47 matched controls. We found two patients positive for NMDAR-Abs (3.3%). One of them was eventually considered to have been misdiagnosed and reclassified as encephalitis. The other met the criteria for bipolar I disorder, presented no neurological symptoms and had a comorbid HIV infection of vertical transmission. This is the first reported case of an HIV-infected patient with psychosis associated with NSAs. This study shows that patients presenting with clinically incomplete forms of anti-NMDAR encephalitis, with predominant or isolated psychiatric symptoms, can remain undetected if no ancillary tests are performed. To improve patient diagnosis and treatment of individuals with a first psychotic episode, more detailed neurological examinations might be needed. Further studies are required to better clarify the role of NSAs in the neuropsychiatric effects of HIV infection. PMID- 26996306 TI - A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing. AB - Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses. PMID- 26996307 TI - Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity. AB - Guanylate binding proteins (GBPs) are an interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) with well-established activity against intracellular bacteria and parasites. Here we show that GBP5 potently restricts HIV-1 and other retroviruses. GBP5 is expressed in the primary target cells of HIV-1, where it impairs viral infectivity by interfering with the processing and virion incorporation of the viral envelope glycoprotein (Env). GBP5 levels in macrophages determine and inversely correlate with infectious HIV-1 yield over several orders of magnitude, which may explain the high donor variability in macrophage susceptibility to HIV. Antiviral activity requires Golgi localization of GBP5, but not its GTPase activity. Start codon mutations in the accessory vpu gene from macrophage-tropic HIV-1 strains conferred partial resistance to GBP5 inhibition by increasing Env expression. Our results identify GBP5 as an antiviral effector of the IFN response and may explain the increased frequency of defective vpu genes in primary HIV-1 strains. PMID- 26996308 TI - Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2. AB - Activating mutations in protein kinases drive many cancers. While how recurring point mutations affect kinase activity has been described, the effect of in-frame deletions is not well understood. We show that oncogenic deletions within the beta3-alphaC loop of HER2 and BRAF are analogous to the recurrent EGFR exon 19 deletions. We identify pancreatic carcinomas with BRAF deletions mutually exclusive with KRAS mutations. Crystal structures of BRAF deletions reveal the truncated loop restrains alphaC in an active "in" conformation, imparting resistance to inhibitors like vemurafenib that bind the alphaC "out" conformation. Characterization of loop length explains the prevalence of five amino acid deletions in BRAF, EGFR, and HER2 and highlights the importance of this region for kinase activity and inhibitor efficacy. PMID- 26996310 TI - Consumers' willingness to pay for nutritional claims fighting the obesity epidemic: the case of reduced-fat and low salt cheese in Spain. AB - OBJECTIVES: The aim of this study was to investigate consumers' willingness to pay (WTP) for cheeses bearing reduced-fat and low salt claims in Spain. STUDY DESIGN: An experiment with 219 cheese consumers was conducted in the period March May 2015. We used different versions of cheese bearing reduced-fat and low salt claims. METHODS: A choice experiment was used to estimate WTP for reduced-fat and/or low salt cheeses. Participants faced eight choice sets, each consisting of two packages of cheese with different combinations of two claims. Individuals chose one of the two packages of cheese in each choice set, or decided not to choose either. Moreover, to consider possible heterogeneity in WTP across consumers, a random parameters logit model (RPL), a Chi-squared test, and analysis of variance tests were used. RESULTS: Spanish cheese consumers were willing to pay a positive premium for packages of cheese with reduced-fat claims (?0.538/100 g), and for cheese with reduced-fat and low salt claims (?1.15/100 g). Conversely, consumers valued low-salt content claims negatively. They preferred to pay ?0.38/100 g for a conventional cheese rather than one low in salt content. As there was heterogeneity in consumers' WTP, two different consumer segments were identified. Segment 1 consisted of normal weight and younger consumers with higher incomes and levels of education, who valued low salt cheese more negatively than those individuals in Segment 2, predominantly comprising overweight and older consumers with low income and educational level. This means that individuals in Segment 1 would pay more for conventional cheese (?1/100 g) than those in Segment 2 (?0.50/100 g). However, no difference between the two segments was found in WTP for reduced-fat cheese. CONCLUSIONS: The findings suggest that consumers are willing to pay a price premium for a package of cheese with a reduced-fat claim or cheese with reduced-fat and low salt claims appearing together; however, they are not willing to pay for a package of cheese with only a low salt claim. In comparison with overweight people, normal weight consumers would prefer to pay more for conventional cheese than low salt cheese. Finally, the results of this study contribute to insights in the promotion of healthier food choices among consumers. In this regard, outreach activities promoted by food companies could drive consumers to increase their knowledge of the benefits of eating reduced-fat and low salt food products in relation to their health status. PMID- 26996312 TI - Unambiguous characterization of anisotropic foldamer packing in a foldecture with an elongated hexagonal plate shape. AB - Herein we correlate secondary structure perturbation with changes in the solid state molecular architectures of an elongated hexagonal plate-shaped foldecture derived from the self-assembly of rigid 12-helical beta-peptide foldamers to which a flexible C-terminus alpha-leucine moiety has been appended. This study provides the first complete characterization of the directional molecular packing patterns of individual foldamer components within a foldecture, from which a 3D molecular-level picture of the entire foldecture was unambiguously constructed. PMID- 26996311 TI - A comparison of secondary prevention practice in poststroke and coronary heart disease patients. AB - OBJECTIVES: It is evident that patients with atherosclerotic vascular disease (AVD) benefit from appropriate secondary prevention. In clinical reality, the secondary prevention in AVD patients other than those with coronary heart disease (CHD) is often overlooked. Therefore, we compared the adherence to secondary prevention principles between poststroke and CHD patients. STUDY DESIGN: Descriptive (cross-sectional) study with prospective mortality follow-up. METHODS: We examined 1729 chronic patients with AVD (mean age 65.9 (+/-SD 9.6) years), 964 with CHD, and 765 poststroke (pooled data of Czech samples of EUROASPIRE III, IV, and the ESH stroke survey). The interview was performed 6-36 months after the coronary event/revascularization or the first ischemic stroke, while the mortality follow-up 5 years after this interview. RESULTS: Poststroke patients had a significantly higher risk of persistent smoking, blood pressure >=140/90 mmHg and LDL >=2.5 mmol/L than CHD patients [odds ratios adjusted for age, gender and survey were 1.63 (95% CI: 1.13-2.33), 1.38 (95% CI: 1.13-1.69) and 2.26 (95% CI: 1.84-2.78), respectively]. In contrast, poststroke patients showed a lower risk of inappropriate glucose control and hypertriglyceridemia [0.66 (95%CI: 0.54-0.82) and 0.74 (95%CI: 0.61-0.91), respectively]. The prescription rates of antiplatelets/anticoagulants, antihypertensives and statins were also significantly lower in poststroke than in CHD patients (89.4 vs 93.7, 85.9 vs 97.5, and 57.7 vs 89.8, respectively). Mortality analysis was performed in a subsample of 815 subjects interviewed in 2006/07. The 5-year all-cause mortality rates were 25.8% and 13.3% in poststroke and coronary patients, respectively (P = 0.0023); the hazard ratio for stroke adjusted for major risk factors was 1.85 (95% CI: 1.31-2.63). CONCLUSIONS: Compared to CHD patients, poststroke patients are strongly handicapped in terms of poor adherence to secondary prevention target, prescription of basic pharmacotherapies and mortality risk. PMID- 26996313 TI - Whole genome sequencing provides insights into the genetic determinants of invasiveness in Salmonella Dublin. AB - Salmonella enterica subsp. enterica serovar Dublin (S. Dublin) is one of the non typhoidal Salmonella (NTS); however, a relatively high proportion of human infections are associated with invasive disease. We applied whole genome sequencing to representative invasive and non-invasive clinical isolates of S. Dublin to determine the genomic variations among them and to investigate the underlying genetic determinants associated with invasiveness in S. Dublin. Although no particular genomic variation was found to differentiate in invasive and non-invasive isolates four virulence factors were detected within the genome of all isolates including two different type VI secretion systems (T6SS) encoded on two Salmonella pathogenicity islands (SPI), including SPI-6 (T6SSSPI-6) and SPI-19 (T6SSSPI-19), an intact lambdoid prophage (Gifsy-2-like prophage) that contributes significantly to the virulence and pathogenesis of Salmonella serotypes in addition to a virulence plasmid. These four virulence factors may all contribute to the potential of S. Dublin to cause invasive disease in humans. PMID- 26996309 TI - Spontaneous Hepatocellular Carcinoma after the Combined Deletion of Akt Isoforms. AB - Akt is frequently hyperactivated in human cancers and is targeted for cancer therapy. However, the physiological consequences of systemic Akt isoform inhibition were not fully explored. We showed that while combined Akt1 and Akt3 deletion in adult mice is tolerated, combined Akt1 and Akt2 deletion induced rapid mortality. Akt2(-/-) mice survived hepatic Akt1 deletion but all developed spontaneous hepatocellular carcinoma (HCC), which is associated with FoxO dependent liver injury and inflammation. The gene expression signature of HCC bearing livers is similar to aggressive human HCC. Consistently, neither Akt1(-/ ) nor Akt2(-/-) mice are resistant to diethylnitrosamine-induced hepatocarcinogenesis, and Akt2(-/-) mice display a high incidence of lung metastasis. Thus, in contrast to other cancers, hepatic Akt inhibition induces liver injury that could promote HCC. PMID- 26996314 TI - Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats. AB - Although it is widely accepted that nicotine plays a key role in tobacco dependence, nicotine alone cannot account for all of the pharmacological effects associated with cigarette smoke found in preclinical models. Thus, the present study aimed to determine the differential effects of the interoceptive cues of nicotine alone versus those of cigarette smoke condensate (CSC) in nicotine trained rats. First, the rats were trained to discriminate nicotine (0.4mg/kg, subcutaneous [s.c.]) from saline in a two-lever drug discrimination paradigm. Then, to clarify the different neuropharmacological mechanisms underlying the discriminative-stimulus effects in the nicotine and CSC in nicotine-trained rats, either the alpha4beta2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-beta-erythroidine (DHbetaE; 0.3-1.0mg/kg, s.c.) or the alpha7 nAChR antagonist methyllycaconitine citrate (MLA; 5-10mg/kg, intraperitoneal [i.p.]) was administered prior to the injection of either nicotine or CSC. Separate set of experiments was performed to compare the duration of action of the discriminative-stimulus effects of CSC and nicotine. CSC exhibited a dose dependent nicotine generalization, and interestingly, 1.0mg/kg of DHbetaE antagonized the discriminative effects of nicotine (0.4mg/kg) but not CSC (0.4mg/kg nicotine content). However, pretreatment with MLA had no effect. In the time-course study, CSC had a relatively longer half-life in terms of the discriminative-stimulus effects compared with nicotine alone. Taken together, the present findings indicate that CSC has a distinct influence on interoceptive effects relative to nicotine alone and that these differential effects might be mediated, at least in part, by the alpha4beta2, but not the alpha7, nAChR. PMID- 26996315 TI - Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia. AB - A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further. PMID- 26996316 TI - Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property. AB - Swertisin, a C-glucosylflavone isolated from Swertia japonica, has been known to have anti-inflammatory or antidiabetic activities. Until yet, however, its cognitive function is not investigated. In the present study, we endeavored to elucidate the effects of swertisin on cholinergic blockade-induced memory impairment. Swertisin (5 or 10mg/kg, p.o.) significantly ameliorated scopolamine induced cognitive impairment in the several behavioral tasks. Also, single administration of swertisin (10mg/kg, p.o.) in normal naive mice enhanced the latency time in the passive avoidance task. In addition, the ameliorating effect of swertisin on scopolamine-induced memory impairment was significantly antagonized by a sub-effective dose of N6-cyclopentyladenosine (CPA, 0.1mg/kg, i.p). The adenosine A1 receptor antagonistic property of swertisin was confirmed by receptor binding assay. Furthermore, the administration of swertisin significantly increased the phosphorylation levels of hippocampal or cortical protein kinase A (PKA, 5 or 10mg/kg) and CREB (10mg/kg), and co-administration of CPA (0.1mg/kg, i.p) blocked the increased phosphorylated levels of PKA and CREB in the both cortex and hippocampus. Taken together, these results indicate that the memory-ameliorating effects of swertisin may be, in part, mediated through the adenosinergic neurotransmitter system, and that swertisin may be useful for the treatment of cognitive dysfunction observed in several diseases such as Alzheimer's disease. PMID- 26996318 TI - Facile synthesis of enantioenriched phenol-sulfoxides and their aluminum complexes. AB - Chiral phenolic p-tolylsulfoxides and t-butylsulfoxides were prepared by several short synthetic routes starting from readily available starting materials. The key synthetic step was the reaction of lithiated arenes with menthyl sulfinates or enantioselective oxidation of a t-butyl sulfide. Well-defined neutral ligand AlMe2 complexes were obtained by stoichiometric treatment with AlMe3. PMID- 26996317 TI - Active temporal multiplexing of indistinguishable heralded single photons. AB - It is a fundamental challenge in quantum optics to deterministically generate indistinguishable single photons through non-deterministic nonlinear optical processes, due to the intrinsic coupling of single- and multi-photon-generation probabilities in these processes. Actively multiplexing photons generated in many temporal modes can decouple these probabilities, but key issues are to minimize resource requirements to allow scalability, and to ensure indistinguishability of the generated photons. Here we demonstrate the multiplexing of photons from four temporal modes solely using fibre-integrated optics and off-the-shelf electronic components. We show a 100% enhancement to the single-photon output probability without introducing additional multi-photon noise. Photon indistinguishability is confirmed by a fourfold Hong-Ou-Mandel quantum interference with a 91 +/- 16% visibility after subtracting multi-photon noise due to high pump power. Our demonstration paves the way for scalable multiplexing of many non-deterministic photon sources to a single near-deterministic source, which will be of benefit to future quantum photonic technologies. PMID- 26996319 TI - Synergy of metal and nonmetal dopants for visible-light photocatalysis: a case study of Sn and N co-doped TiO2. AB - This paper mainly focuses on the synergistic effect of Sn and N dopants to enhance the photocatalytic performance of anatase TiO2 under visible light or simulated solar light irradiation. The Sn and N co-doped TiO2 (SNT-x) photocatalysts were successfully prepared by the facile sol-gel method and the post-nitridation route in the temperature range of 400-550 degrees C. All the as prepared samples were characterized in detail by X-ray diffraction, UV-vis diffuse reflectance spectroscopy, transmission electron microscopy, X-ray photoelectron and electron spin resonance spectroscopy and photoelectrochemical measurements. The characterization results reveal that the co-incorporation of Sn and N atoms remarkably modifies the electronic structure of TiO2, which gives rise to a prominent separation of photogenerated charge carriers and more efficient interfacial charge-transfer reactions in a photocatalytic process. The enhanced photocatalytic activity is attributed to the intensified active oxygen species including hydroxyl radicals (OH) and superoxide anion radicals (O2(-)) for degradation of organic pollutants. And the result of photocatalytic hydrogen production further confirms the existence of the synergistic effect in the SNT-x samples, because they exhibit higher photocatalytic activity than the sum of N/TiO2 and Sn/TiO2. This work provides a paradigm to consolidate the understanding of the synergistic effect of metal and non-metal co-doped TiO2 in domains of photocatalysis and photoelectrochemistry. PMID- 26996320 TI - First feed affects the expressions of microRNA and their targets in Atlantic cod CORRIGENDUM. PMID- 26996321 TI - Proximity-enabled bioreactivity to generate covalent peptide inhibitors of p53 Mdm4. AB - Although small molecule covalent inhibitors have been widely explored, macromolecular covalent inhibitors are more difficult to design and implement. Here we present a strategy to enable a peptide to bind to its target protein covalently via proximity-enabled bioreactivity, improving its activity of inhibiting the p53-Mdm4 interaction by 10-fold. PMID- 26996324 TI - Structural transformation during Li/Na insertion and theoretical cyclic voltammetry of the delta-NH4V4O10 electrode: a first-principles study. AB - A double layer delta-NH4V4O10, due to its high energy storage capacity and excellent rate capability, is a very promising cathode material for Li-ion and Na ion batteries for large-scale renewable energy storage in transportation and smart grids. While it possesses better stability, and higher ionic and electronic conductivity than the most widely explored V2O5, the mechanisms of its cyclability are yet to be understood. Here, we present a theoretical cyclic voltammetry as a tool based on first-principles calculations, and uncover structural transformations that occur during Li(+)/Na(+) insertion (x) into (Lix/Nax)NH4V4O10. Structural distortions associated with single-phase and multi phase structural changes during the insertion of Li(+)/Na(+), identified through the analysis of voltage profile and theoretical cyclic voltammetry are in agreement with the reported experimental electrochemical measurements on delta NH4V4O10. We obtain an insight into its electronic structure with a lower band gap that is responsible for the high rate capability of (Lix/Nax) delta-NH4V4O10. The scheme of theoretical cyclic voltammetry presented here will be useful for addressing issues of cyclability and energy rate in other electrode materials. PMID- 26996323 TI - Gradient Permittivity Meta-Structure model for Wide-field Super-resolution imaging with a sub-45 nm resolution. AB - A gradient permittivity meta-structure (GPMS) model and its application in super resolution imaging were proposed and discussed in this work. The proposed GPMS consists of alternate metallic and dielectric films with a gradient permittivity which can support surface plasmons (SPs) standing wave interference patterns with a super resolution. By employing the rigorous numerical FDTD simulation method, the GPMS was carefully simulated to find that the period of the SPs interference pattern is only 84 nm for a 532 nm incident light. Furthermore, the potential application of the GPMS for wide-field super-resolution imaging was also discussed and the simulation results show that an imaging resolution of sub-45 nm can be achieved based on the plasmonic structure illumination microscopic method, which means a 5.3-fold improvement on resolution has been achieved in comparison with conventional epifluorescence microscopy. Moreover, besides the super resolution imaging application, the proposed GPMS model can also be applied for nanolithography and other areas where super resolution patterns are needed. PMID- 26996322 TI - Ciliary IFT80 balances canonical versus non-canonical hedgehog signalling for osteoblast differentiation. AB - Intraflagellar transport proteins (IFT) are required for hedgehog (Hh) signalling transduction that is essential for bone development, however, how IFT proteins regulate Hh signalling in osteoblasts (OBs) remains unclear. Here we show that deletion of ciliary IFT80 in OB precursor cells (OPC) in mice results in growth retardation and markedly decreased bone mass with impaired OB differentiation. Loss of IFT80 blocks canonical Hh-Gli signalling via disrupting Smo ciliary localization, but elevates non-canonical Hh-Galphai-RhoA-stress fibre signalling by increasing Smo and Galphai binding. Inhibition of RhoA and ROCK activity partially restores osteogenic differentiation of IFT80-deficient OPCs by inhibiting non-canonical Hh-RhoA-Cofilin/MLC2 signalling. Cytochalasin D, an actin destabilizer, dramatically restores OB differentiation of IFT80-deficient OPCs by disrupting actin stress fibres and promoting cilia formation and Hh-Gli signalling. These findings reveal that IFT80 is required for OB differentiation by balancing between canonical Hh-Gli and non-canonical Hh-Galphai-RhoA pathways and highlight IFT80 as a therapeutic target for craniofacial and skeletal abnormalities. PMID- 26996326 TI - Operationally simple hydrotrifluoromethylation of alkenes with sodium triflinate enabled by Ir photoredox catalysis. AB - We report herein a single component Ir photoredox catalyst which is capable of catalyzing the hydrotrifluoromethylation of terminal alkenes and Michael acceptors with sodium triflinate (Langlois reagent) in methanol under irradiation at room temperature. Various synthetically useful functional groups, including ester, amide, ether, aldehyde, sulfone, ketone and aryl boronate, are well tolerated in this reaction. PMID- 26996327 TI - PbTiO3(001) Capped with ZnO(1120): An ab Initio Study of Effect of Substrate Polarization on Interface Composition and CO2 Dissociation. AB - Catalytic conversion of CO2 into useful chemicals is an attractive alternative to expensive physical carbon sequestration methods. However, this approach is challenging because current chemical conversion methods employ high temperatures or pressures, thereby increasing cost and potentially leading to net carbon positive processes. In this paper, we examine the interface properties of ZnO(1120)/PbTiO3 and its surface interaction with CO2, CO and O. We show that the stoichiometry of the stable interface is dependent on the substrate polarization and can be controlled by changing the growth conditions. Using a model reaction, we demonstrate that a dynamically tuned catalysis scheme could enable significantly lower-energy approaches for CO2 conversion. PMID- 26996325 TI - In vivo imaging of prostate cancer using an anti-PSMA scFv fragment as a probe. AB - We aimed to evaluate a fluorescent-labeled single chain variable fragment (scFv) of the anti-PSMA antibody as a specific probe for the detection of prostate cancer by in vivo fluorescence imaging. An orthotopic model of prostate cancer was generated by injecting LNCaP cells into the prostate lobe. ScFvD2B, a high affinity anti-PSMA antibody fragment, was labeled using a near-infrared fluorophore to generate a specific imaging probe (X770-scFvD2B). PSMA-unrelated scFv-X770 was used as a control. Probes were injected intravenously into mice with prostate tumors and fluorescence was monitored in vivo by fluorescence molecular tomography (FMT). In vitro assays showed that X770-scFvD2B specifically bound to PSMA and was internalized in PSMA-expressing LNCaP cells. After intravenous injection, X770-scFvD2B was detected in vivo by FMT in the prostate region. On excised prostates the scFv probe co-localized with the cancer cells and was found in PSMA-expressing cells. The PSMA-unrelated scFv used as a control did not label the prostate cancer cells. Our data demonstrate that scFvD2B is a high affinity contrast agent for in vivo detection of PSMA-expressing cells in the prostate. NIR-labeled scFvD2B could thus be further developed as a clinical probe for imaging-guided targeted biopsies. PMID- 26996328 TI - Hypertension: Regulation of salt appetite and blood pressure. PMID- 26996330 TI - Cystic kidney disease: mTORC1-PC-1 crosstalk in TSC. PMID- 26996329 TI - Mineral metabolism: The perils of a falling PTH due to high dialysate calcium. PMID- 26996331 TI - Advanced colorectal neoplasia: Response to Parra del Riego. PMID- 26996332 TI - Azithromycin for the Treatment of Ciclosporin-Induced Gingival Hyperplasia. PMID- 26996333 TI - Reflectance Confocal Microscopy for Inflammatory Skin Diseases. AB - In vivo reflectance confocal microscopy (RCM) is a relatively novel non-invasive tool for microscopic evaluation of the skin used prevalently for diagnosis and management of skin tumour. Its axial resolution, its non-invasive and easy clinical application represents the goals for a large diffusion of this technique. During the last 15 years, RCM has been demonstrated to be able to increase the sensibility and sensitivity of dermoscopy in the diagnosis of skin tumours integrating in real time clinic, dermoscopic and microscopic information useful for the definition of malignancy. Despite to date, no large comparative studies on inflammatory skin diseases has been published in the literature, several papers already showed that RCM has a potential for the evaluation of the descriptive features of the most common inflammatory skin diseases as psoriasis, lupus erythematosus, contact dermatitis and others. The aim of the application of this technique in non-neoplastic skin diseases has been prevalently focused on the possibility of clinical diagnosis confirmation, as well as therapeutic management. Moreover, the use of RCM as driver for an optimised skin biopsy has been also followed in order to reduce the number of unsuccessful histopathological examination. In this review article we describe the confocal features of the major groups of inflammatory skin disorders focusing on psoriasiform dermatitis, interface dermatitis and spongiotic dermatitis. PMID- 26996334 TI - Initial Evaluation of Patients with Pigmented Skin Lesions. PMID- 26996335 TI - Down-regulation of tumor endothelial marker 8 suppresses cell proliferation mediated by ERK1/2 activity. AB - Tumor endothelial marker 8 (TEM8) was recently suggested as a putative anti-tumor target in several types of human cancer based on its selective overexpression in tumor versus normal endothelial cells. The objective of this study was to detect the potential functions of TEM8 in osteosarcoma. Overall, TEM8 was mainly located in cytoplasm and was up-regulated in osteosarcoma compared to benign bone lesions and adjacent non tumor tissue (ANT). High TEM8 expression group had a significant lower overall survival rate than that in the low TEM8 expression group. TEM8 knock-down by siRNA or shRNA results in significant reduction of osteosarcoma cell growth and proliferation both in vitro and in vivo. Ablation of TEM8 led to increasing of p21 and p27 and suppression of cyclin D1 mediated by Erk1/2 activity. These findings suggest that down-regulation of TEM8 play an important role in the inhibition of tumorigenesis and development of osteosarcoma. PMID- 26996336 TI - Differential response of patient-derived primary glioblastoma cells to environmental stiffness. AB - The ability of cancer cells to sense external mechanical forces has emerged as a significant factor in the promotion of cancer invasion. Currently there are conflicting reports in the literature with regard to whether glioblastoma (GBM) brain cancer cell migration and invasion is rigidity-sensitive. In order to address this question we have compared the rigidity-response of primary patient derived GBM lines. Cells were plated on polyacrylamide gels of defined rigidity that reflect the diversity of the brain tissue mechanical environment, and cell morphology and migration were analysed by time-lapse microscopy. Invasiveness was assessed in multicellular spheroids embedded in 3D matrigel cultures. Our data reveal a range of rigidity-dependent responses between the patient-derived cell lines, from reduced migration on the most compliant tissue stiffness to those that are insensitive to substrate rigidity and are equally migratory irrespective of the underlying substrate stiffness. Notably, the rigidity-insensitive GBM cells show the greatest invasive capacity in soft 3D matrigel cultures. Collectively our data confirm both rigidity-dependent and independent behaviour in primary GBM patient-derived cells. PMID- 26996338 TI - Plasticity in plant functional traits is shaped by variability in neighbourhood species composition. AB - Plant functional traits can vary widely as a result of phenotypic plasticity to abiotic conditions. Trait variation may also reflect responses to the identity of neighbours, although not all species are equally responsive to their biotic surroundings. We hypothesized that responses to neighbours are shaped by spatial community patterns and resulting variability in neighbour composition. More precisely, we tested the theoretical prediction that plasticity is most likely to evolve if alternative environments (in this case, different neighbour species) are common and encountered at similar frequencies. We estimated the frequencies of encountering different neighbour species in the field for 27 grassland species and measured the aboveground morphological responses of each species to conspecific vs heterospecific neighbours in a common garden. Responses to neighbour identity were dependent on how frequently the experimental neighbours were encountered by the focal species in their home community, with the greatest plasticity observed in species that encountered both neighbours (conspecific and heterospecific) with high and even frequency. Biotic interactions with neighbouring species can impose selection on plasticity in functional traits, which may feed back through trait divergence and niche differentiation to influence species coexistence and community structure. PMID- 26996337 TI - A Novel IgM-capture enzyme-linked immunosorbent assay using recombinant Vag8 fusion protein for the accurate and early diagnosis of Bordetella pertussis infection. AB - An ELISA that measures anti-PT IgG antibody has been used widely for the serodiagnosis of pertussis; however, the IgG-based ELISA is inadequate for patients during the acute phase of the disease because of the slow response of anti-PT IgG antibodies. To solve this problem, we developed a novel IgM-capture ELISA that measures serum anti-Bordetella pertussis Vag8 IgM levels for the accurate and early diagnosis of pertussis. First, we confirmed that Vag8 was highly expressed in all B. pertussis isolates tested (n = 30), but little or none in other Bordetella species, and that DTaP vaccines did not induce anti-Vag8 IgG antibodies in mice (i.e. the antibody level could be unaffected by the vaccination). To determine the immune response to Vag8 in B. pertussis infection, anti-Vag8 IgM levels were compared between 38 patients (acute phase of pertussis) and 29 healthy individuals using the anti-Vag8 IgM-capture ELISA. The results revealed that the anti-Vag8 IgM levels were significantly higher in the patients compared with the healthy individuals (P < 0.001). ROC analysis also showed that the anti-Vag8 IgM-capture ELISA has higher diagnostic accuracy (AUC, 0.92) than a commercial anti-PT IgG ELISA kit. Moreover, it was shown that anti-Vag8 IgM antibodies were induced earlier than anti-PT IgG antibodies on sequential patients' sera. These data indicate that our novel anti-Vag8 IgM-capture ELISA is a potentially useful tool for making the accurate and early diagnosis of B. pertussis infection. PMID- 26996339 TI - Fellow Eye Comparisons for 7-Year Outcomes in Ranibizumab-Treated AMD Subjects from ANCHOR, MARINA, and HORIZON (SEVEN-UP Study). AB - PURPOSE: To compare study and fellow eyes in subjects with age-related macular degeneration (AMD) for 7-year outcomes arising from contrasting treatment histories and disease statuses. DESIGN: Multicenter cohort study, predetermined secondary analysis. PARTICIPANTS: A total of 65 participants from the ranibizumab treatment arms of the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR), Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab In the Treatment of Neovascular AMD (MARINA), and Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (HORIZON) trials, recruited for an update evaluation from 14 study sites. METHODS: Seven-year visual outcomes and retinal imaging data were compared with the ANCHOR, MARINA, and HORIZON databases. Under the ANCHOR and MARINA protocols, study eyes had received monthly ranibizumab injections for the initial 2 years, during which fellow eyes were prohibited from anti-vascular endothelial growth factor (VEGF) treatments. MAIN OUTCOME MEASURES: Percentage of subjects with study eye vision better than fellow eye, vision change from baseline to year 7, and mean area of macular atrophy (MA) were predetermined secondary end points. RESULTS: Fellow eyes with exudative AMD had received a mean 7.3 total injections of anti-VEGF agents in the mean 3.4 years off-study. For the 35% of subjects with exudative AMD in both eyes at baseline, within-patient comparisons at year 7 showed better vision in the study eye in 82%, with better mean final vision in study eyes (54.7 vs. 27.3 letters in fellow eyes, P < 0.001). Also in this subgroup, study eyes, which had received 2 years of high-frequency ranibizumab, had less severe MA than the respective fellow eye at year 7 in 88% of patients (mean area +/- standard deviation 2.8+/-2.2 mm(2) vs. 5.8+/-2.5 mm(2) in the fellow eyes, P = 0.0013). Final fellow eye vision outcome was significantly correlated with MA severity (coefficient -6.95, P < 0.001), and patients' inter eye vision difference corresponded to the degree of MA asymmetry. CONCLUSIONS: Exudative fellow eyes remained at risk for further vision decline in later years under management with low-frequency anti-VEGF therapy. In patients with bilateral exudative AMD at baseline, final vision at year 7 was significantly better in study eyes than in fellow eyes, and MA was less severe. Macular atrophy area correlated with final visual outcomes, determined inter-eye vision differences, and was not attributable to high-frequency ranibizumab therapy. PMID- 26996341 TI - Manifestations of Complement-Mediated and Immune Complex-Mediated Membranoproliferative Glomerulonephritis: A Comparative Consecutive Series. AB - PURPOSE: Membranoproliferative glomerulonephritis (MPGN) recently was reclassified to reflect the underlying cause as a complement-mediated and immune complex-mediated disease. This classification is based on renal biopsy immunofluorescence examination, making the former electron-microscopy classification obsolete. In this report, we describe related eye findings in patients with MPGN based on the new classification. DESIGN: Retrospective case series. PARTICIPANTS: All Mayo Clinic Rochester patients with pathology-confirmed complement- and immune complex-mediated MPGN who had available ophthalmology records from 1997 through 2014 were included in this study. METHODS: The medical and pathologic records of patients with MPGN and eye examination results were reviewed from years 1997 through 2014. MAIN OUTCOME MEASURES: The number of patients and the number of eyes with MPGN-related pathologic features were examined. Visual acuity also was considered. RESULTS: There were 23 patients with complement-mediated MPGN and available eye examination results. Of these, 9 patients (39%) and 17 eyes (37%) had retinal pathologic features that likely were related to the same underlying pathophysiologic process as their renal disease. Five patients (22%) and 6 eyes (13%) had significant vision loss. There were 23 patients with immune complex-mediated MPGN and available eye examination results. Only 2 (9%) of these patients (4 eyes) had retinal pathologic features that potentially could be related to the same underlying pathophysiologic process as their renal disease, and neither had vision loss. CONCLUSIONS: Retinal abnormalities are more prominent among patients with complement-mediated MPGN when compared with patients with immune complex-mediated MPGN. It is critical for ophthalmologists to recognize the updated MPGN classification system, and all patients with complement-mediated MPGN require screening eye examinations. PMID- 26996342 TI - An efficient SCNT technology for the establishment of personalized and public human pluripotent stem cell banks. AB - Although three different research groups have reported successful derivations of human somatic cell nuclear transfer-derived embryonic stem cell (SCNT-ESC) lines using fetal, neonatal and adult fibroblasts, the extremely poor development of cloned embryos has hindered its potential applications in regenerative medicine. Recently, however, our group discovered that the severe methylation of lysine 9 in Histone H3 in a human somatic cell genome was a major SCNT reprogramming barrier, and the overexpression of KDM4A, a H3K9me3 demethylase, significantly improved the blastocyst formation of SCNT embryos. In particular, by applying this new approach, we were able to produce multiple SCNT-ES cell lines using oocytes obtained from donors whose eggs previously failed to develop to the blastocyst stage. Moreover, the success rate was closer to 25%, which is comparable to that of IVF embryos, so that our new human SCNT method seems to be a practical approach to establishing a pluripotent stem cell bank for the general public as well as for individual patients. [BMB Reports 2016; 49(4): 197-198]. PMID- 26996340 TI - Previous Intravitreal Therapy Is Associated with Increased Risk of Posterior Capsule Rupture during Cataract Surgery. AB - PURPOSE: To investigate if previous intravitreal therapy is a predictor of posterior capsule rupture (PCR) during cataract surgery. DESIGN: Multicenter, national electronic medical record (EMR) database study with univariate and multivariate regression modeling. PARTICIPANTS: A total of 65 836 eyes of 44 635 patients undergoing cataract surgery. METHODS: Anonymized data were extracted for eyes undergoing cataract surgery from 20 hospitals using the same EMR for cases performed between 2004 and 2014. Variables included as possible risk indicators for PCR were age, sex, number of previous intravitreal injections, indication for intravitreal therapy, grade of healthcare professional administering intravitreal therapy, advanced cataract, and cataract surgeon grade. MAIN OUTCOME MEASURES: Presence or absence of posterior capsular rupture during cataract surgery. RESULTS: Data were available on 65 836 cataract operations, of which 1935 had undergone previous intravitreal therapy (2.9%). In univariate regression analyses, patient age, advanced cataract, junior cataract surgeon grade, and number of previous intravitreal injections were significant predictors of PCR. By considering the number of previous intravitreal injections as a continuous variable, the odds ratio for PCR per intravitreal injection was 1.04 (P = 0.016) after adjusting for age, advanced cataract, and cataract surgeon grade. Repeat analysis considering intravitreal injections as a categoric variable showed 10 or more previous injections were associated with a 2.59 times higher likelihood of PCR (P = 0.003) after again adjusting for other significant independent predictors. CONCLUSIONS: Previous intravitreal therapy is associated with a higher likelihood of PCR during cataract surgery. This study provides data to help inform surgeons and patients about the risk of complications when undergoing cataract surgery after multiple prior intravitreal injections. Further investigation is required to determine the cause behind the increased PCR risk. PMID- 26996343 TI - MiR-146 and miR-125 in the regulation of innate immunity and inflammation. AB - Innate immune responses are primary, relatively limited, and specific responses to numerous pathogens and toxic molecules. Protein expression involved in these innate responses must be tightly regulated at both transcriptional level and post transcriptional level to avoid the development of excessive inflammation that can be potentially harmful to the host. MicroRNAs are small noncoding RNAs (~22 nucleotides [nts]) that participate in the regulation of numerous physiological responses by targeting specific messenger RNAs to suppress their translation. Recent work has shown that several negative regulators of transcription including microRNAs play important roles in inhibiting the exacerbation of inflammatory responses and in the maintenance of immunological homeostasis. This emerging research area will provide new insights on how microRNAs regulate innate immune signaling. It might show that dysregulation of microRNA synthesis is associated with the pathogenesis of inflammatory and infectious diseases. In this review, we focused on miR-146 and miR-125 and described the roles these miRNAs in modulating innate immune signaling. These microRNAs can control inflammatory responses and the outcomes of pathogenic infections. [BMB Reports 2016; 49(6): 311-318]. PMID- 26996344 TI - Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death. AB - Loss of pancreatic beta-cells by oxidative stress or cytokines is associated with diabetes mellitus (DM). DJ-1 is known to as a multifunctional protein, which plays an important role in cell survival. We prepared cell permeable wild type (WT) and mutant type (M26I) Tat-DJ-1 proteins to investigate the effects of DJ-1 against combined cytokines (IL-1beta, IFN-gamma and TNF-alpha)-induced RINm5F cell death. Both Tat-DJ-1 proteins were transduced into RINm5F cells. WT Tat-DJ-1 proteins significantly protected against cell death from cytokines by reducing intracellular toxicities. Also, WT Tat-DJ-1 proteins markedly regulated cytokines induced pro- and anti-apoptosis proteins. However, M26I Tat-DJ-1 protein showed relatively low protective effects, as compared to WT Tat-DJ-1 protein. Our experiments demonstrated that WT Tat-DJ-1 protein protects against cytokine induced RINm5F cell death by suppressing intracellular toxicities and regulating apoptosisrelated protein expression. Thus, WT Tat-DJ-1 protein could potentially serve as a therapeutic agent for DM and cytokine related diseases. [BMB Reports 2016; 49(5): 297-302]. PMID- 26996346 TI - Allograft and Autograft Transphyseal Anterior Cruciate Ligament Reconstruction in Skeletally Immature Patients: Outcomes and Complications. AB - PURPOSE: The purpose of the study was to evaluate outcomes, graft failure rates, and complications after transphyseal soft-tissue allograft and autograft anterior cruciate ligament (ACL) reconstruction (ACLR) in patients with open growth plates. METHODS: Twenty-nine skeletally immature athletes (30 knees) with a mean age of 13.9 years (range, 9 to 16 years) underwent transphyseal ACLR (22 with quadrupled hamstring autograft and 8 with tibialis anterior allograft). Of the patients, 5 were Tanner stage I, 17 were Tanner stage II, and 7 were Tanner stage III. Outcomes included KT-1000 (MEDmetric, San Diego, CA) measurements and International Knee Documentation Committee (IKDC), Cincinnati, and Lysholm scoring. Radiographs were evaluated for asymmetrical physeal closure, growth arrest lines, and knee alignment. RESULTS: The mean outcomes scores, excluding the 5 graft failures, were 91.8 points for the IKDC score, 93.0 points for the Cincinnati score, and 91.5 points for the Lysholm score at a mean of 4 years' follow-up (range, 24 to 84 months). The 95% confidence intervals for the differences were -27.7 to -18.0 for the IKDC score, -26.4 to -12.1 for the Cincinnati score, and -20.1 to -6.4 for the Lysholm score. One hundred percent of patients ultimately returned to their prior level of sports, but only 76% maintained that level at most recent follow-up. The mean KT-1000 side-to-side difference at most recent follow-up was 0.4 mm (SD, 1.3 mm; range, -2 to 3 mm) (n = 25). Evaluation at a minimum of 2 years postoperatively showed 4 patients with Harris growth arrest lines and 1 genu valgum deformity that spontaneously corrected at latest follow-up. For the remaining 29 knees, there was a mean side to-side difference of 1.3 degrees (range, 0 degrees to 4 degrees ) in the radiographic tibiofemoral angle and 0.2 cm (range, 0 to 1 cm) for clinical leg length measurements. Sports-related graft failure occurred at a mean of 24 months after ACLR in 16.7% of patients (37.5% with allografts [3 of 8] v 9% with autografts [2 of 22], P = .10). In 5 patients (16.7%), a contralateral ACL injury was sustained. CONCLUSIONS: Transphyseal ACLR in patients with open growth plates resulted in a high rate of return to sports with a low rate of growth arrest and deformity at a mean of 4 years' follow-up. Harris growth arrest lines and a case of genu valgum deformity that spontaneously corrected, however, were observed. Graft failure rates and contralateral ACL tears were not insignificant in this young patient population. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26996345 TI - Glycogen synthase kinase 3beta in Toll-like receptor signaling. AB - Toll-like receptors (TLRs) play a critical role in the innate immune response against pathogens. Each TLR recognizes specific pathogen-associated molecular patterns, after which they activate the adaptor protein MyD88 or TRIF-assembled signaling complex to produce immune mediators, including inflammatory cytokines and type I IFNs. Although the activation of TLR is important for host defense, its uncontrolled activation can damage the host. During the past decade, numerous studies have demonstrated that GSK3beta is a key regulator of inflammatory cytokine production in MyD88-mediated TLR signaling via TLR2 and TLR4. Recently, GSK3beta has also been implicated in the TRIF-dependent signaling pathway via TLR3. In this review, we describe current advances on the regulatory role of GSK3beta in immune responses associated with various TLRs. A better understanding of the role of GSK3beta in TLR signaling might lead to more effective anti inflammatory interventions. [BMB Reports 2016; 49(6): 305-310]. PMID- 26996348 TI - Clinical significance of serum vascular endothelial growth factor in young male asthma patients. AB - BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. However, little is known about the potential use of serum levels of VEGF as a biomarker for asthma. We investigated the differences in VEGF levels among normal controls, stable asthma patients, and those with exacerbation of acute asthma. All subjects were young males. METHODS: We measured VEGF levels in each patient group, and examined any serial changes in those with acute exacerbation. RESULTS: VEGF levels were significantly higher in stable asthmatic patients and even more so in acute asthmatic patients, compared to healthy controls. However, there was no correlation between VEGF levels and forced expiratory volume in 1 second in patients with stable asthma. In addition, there were no correlations between VEGF levels and asthma control test scores. In patients with acute exacerbation, VEGF levels significantly increased during the acute period; their levels decreased gradually at 7 and 14 days after treatment. CONCLUSIONS: Compared to normal control patients, the serum levels of VEGF were elevated in stable asthma patients and even more elevated in patients with acute exacerbation. However, the role of VEGF as a biomarker in stable asthma is limited. In patients with acute exacerbation, VEGF levels were associated with clinical improvements. PMID- 26996352 TI - Large-Scale Synthesis of Metal-Ion-Doped Manganese Dioxide for Enhanced Electrochemical Performance. AB - One-dimensional (1D) MnO2 was widely applied in areas of enzyme biosensors, industrial sieves, and energy storage materials owing to its excellent thermal, optical, magnetic, and chemical features. However, its practical application into energy storage devices is often hindered by the bad electronic conductivity (from 10(-5) to 10(-6) S cm(-1)). As is widely known, doping with hetero elements is an efficient way to enhance the electronic conductivity of metal oxides. Herein, a novel and simple molten-salt method is developed to achieve a large-scale preparation of 1D MnO2 nanowires. Such an approach also realizes the easy tuning of electrical properties through doping with different transition metal ions. On the basis of first-principle calculation as well as four-probe measurement, we determined that the conductivity of the doped MnO2 nanowires can be promoted efficiently by utilizing such protocol. Meanwhile, a possible doping route is discussed in detail. As a result, a superior electrochemical performance can be observed in such metal ions (M(+))-doped nanowires. Such high-quality M(+)-doped MnO2 nanowires can satisfy a broad range of application needs beyond the electrochemical capacitors. PMID- 26996347 TI - Glomerular filtration rate affects interpretation of pulmonary function test in a Korean general population: results from the Korea National Health and Nutrition Examination Survey 2010 to 2012. AB - BACKGROUND/AIMS: The pulmonary abnormalities (principally restrictive abnormalities) are characteristic of renal transplant recipients or those with end-stage renal disease. Our aim was to explore whether the prevalence of spirometric abnormalities was influenced by the estimated glomerular filtration rates (GFRs) in a Korean general population. METHODS: We used data obtained during the 2010 to 2012 Korean National Health and Nutrition Examination Survey, a national cross-sectional survey. We analyzed data from subjects for whom spirometric assays and estimated GFRs were of acceptable quality. RESULTS: A total of 8,809 subjects (3,868 male and 4,941 female) was included. In both males and females with GFR values < 60 mL/min/1.73 m2, the linear trends toward the presence of obstructive and restrictive patterns were significant. However, the percent predicted forced vital capacity (FVC) decreased with a decline in the estimated GFR, but only in males (p for trend < 0.0031). Multivariate linear regression analysis showed a decline in the estimated GFR was independently associated with falls in the percent predicted FVC and the forced expiratory volume in 1 second/FVC ratio in both males and females. However, the percent predicted FVC was independently predictive only in males (p = 0.002). CONCLUSIONS: Impaired pulmonary function was associated with a decline in the estimated GFR. The percent predicted FVC decrease paralleled the decline in estimated GFR in male only. Careful interpretation of pulmonary function test data is required in patients with decreased GFRs or impaired renal function, especially males. PMID- 26996353 TI - Range wide molecular data and niche modeling revealed the Pleistocene history of a global invader (Halyomorpha halys). AB - Invasive species' Pleistocene history contains much information on its present population structure, dispersability and adaptability. In this study, the Pleistocene history of a global invasive pest (Brown Marmorated Stink Bug BMSB, Halyomorpha halys) was unveiled using the coupled approach of phylogeography and ecological niche modelling. Rangewide molecular data suggests that the Taiwan and other native populations had diverged in mid-Pleistocene. In mainland China, the native BMSB did not experience population contraction and divergence during last glacial, but persisted in interconnected populations. Combined Bayesian Skyline Plot (BSP) and niche modelling revealed a rapid expansion occurred during the transition of Last Inter Glacial (LIG) to Last Glacial Maximum (LGM). High genetic diversity and multi-reticular haplotypes network exist in the original sources populations of BMSB invasion in northern China. They were speculated to be colonized from the central China, with many derived haplotypes evolved to adapt the novel environment. The ENM future prediction suggest that BMSB may expand northward to higher latitudes in the US and Europe, because of its high invasive ability, together with the available suitable climate space there. PMID- 26996354 TI - An unexpected advantage of insectivorism: insect moulting hormones ingested by song birds affect their ticks. AB - Ecdysteroids are important hormones that regulate moulting in arthropods. Three host ixodid ticks normally moult to the next stage after finishing their blood meal, in the off-host environment. Presumably, three-host ticks that feed on the blood of insectivorous vertebrate hosts can be exposed to high levels of exogenous ecdysteroids causing them to initiate apolysis (the first step of moulting) on the vertebrate host. The aim of the present study was to investigate whether ticks undergo apolysis on insectivorous song birds, and if this phenomenon is associated with the seasonal variation in the availability of moths and with the presence of naturally acquired ecdysteroids in avian blood. During a triannual survey, 3330 hard tick larvae and nymphs were collected from 1164 insectivorous song birds of 46 species. A noteworthy proportion of ticks, 20.5%, showed apolysis. The occurrence of apolytic ticks on birds was correlated with the known seasonality of lepidopteran caterpillars. In addition, 18 blood samples of tick-infested birds were analysed with liquid chromatography - tandem mass spectrometry. Eight samples contained ecdysteroids or their derivatives, frequently in high concentrations, and the presence of these was associated with tick apolysis. In conclusion, naturally acquired ecdysteroids may reach high levels in the blood of insectivorous passerine birds, and will affect ticks (feeding on such blood) by shortening their parasitism. PMID- 26996355 TI - Antifungal activity of a Saharan strain of Actinomadura sp. ACD1 against toxigenic fungi and other pathogenic microorganisms. AB - A new strain of actinobacteria, designated ACD1, was isolated from a Saharan soil sample in the Hoggar region (Algeria). Morphological study led to this strain being classified as a member of the Actinomadura genus. Phylogenetic analysis based on the 16S rRNA gene showed that the strain is closely related to Actinomadura sediminis DSM 45500(T) (98.5% sequence similarity). Furthermore, strain ACD1 presented a strong activity against mycotoxigenic and phytopathogenic fungi, including Aspergillus and Fusarium strains, and other pathogenic microorganisms. The kinetics of antimicrobial activity were investigated on ISP 2, Bennett and TSB media. Four solvents (n-hexane, dichloromethane, ethyl acetate and n-butanol) were used for the extraction of the produced antibiotic. The highest antimicrobial activity was obtained using the butanolic extract from the ISP-2 medium after seven days of fermentation culture. The active antibiotic was purified by reverse-phase HPLC using a C18 column. The UV-visible and mass spectra were determined. The minimum inhibitory concentrations (MIC) of this antibiotic were determined against pathogenic microorganisms. PMID- 26996357 TI - Essential public health functions for countries of the Eastern Mediterranean Region: what are they and what benefits do they offer? PMID- 26996356 TI - Characterization of the Intermediate in and Identification of the Repair Mechanism of (6-4) Photolesions by Photolyases. AB - Quantum mechanics/molecular mechanics calculations are employed to assign previously recorded experimental spectroscopic signatures of the intermediates occurring during the photo-induced repair of (6-4) photolesions by photolyases to specific molecular structures. Based on this close comparison of experiment and theory it is demonstrated that the acting repair mechanism involves proton transfer from the protonated His365 to the N3' nitrogen of the lesion, which proceeds simultaneously with intramolecular OH transfer along an oxetane-like transition state. PMID- 26996358 TI - Examining health care spending trends over a decade: the Palestinian case. AB - An analysis was made of recent health care spending patterns in the occupied Palestinian territory, in order to inform future health policy-making and planning. Data were obtained from the national health accounts for the period 2000-2011. The current level of resource allocation to the health care sector is higher than in many developed countries and is not sustainable. The private sector represents the largest source of health financing (61%) and the burden falls disproportionally on individual households, who account for 63% of private health care expenditure. Key recommendations include: building capacity in the government sector to reduce the outsourcing of health services; modifying inequitable financing mechanisms to reduce the burden on households; and allocating more resources for health promotion and disease prevention programmes. Reorientation of the health system is also needed in terms of reducing the share of spending on inpatient services in favour of more day surgery, outpatient and home-based services. PMID- 26996359 TI - Estimating attributable fraction of lung cancer linked to smoking in Morocco. AB - The objective of this research was to estimate the attributable fraction (AF) of lung cancer linked to smoking in Morocco. The estimation was based on the SAMMEC (Adult Smoking-Attributable Mortality, Morbidity and Economic Costs) method based on the Levin formula to calculate AF linked to tobacco. Data about frequencies, association measures and relative risks were taken from available sources. The AF of lung cancer linked to smoking was about 87%, and around 3049 cases of this cancer in men could be avoided if tobacco use could be prevented. About a 10% reduction in smoking prevalence would result in a reduction of 346 lung cancer cases. Our study provides additional important elements for further advocacy to policy-makers to implement a tobacco control strategy based on a prevention policy in line with the epidemiological situation which could avoid a huge burden on the country. PMID- 26996360 TI - Molecular detection of Leishmania spp. isolated from cutaneous lesions of patients referred to Herat regional hospital, Afghanistan. AB - Cutaneous leishmaniasis is one of the main public health problems in Afghanistan, particularly in Herat. To identify Leishmania spp., molecular techniques were applied to samples from 64 cutaneous leishmaniasis patients referred to Herat regional hospital during 2013. Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis of the ribosomal RNA gene internal transcribed spacer-1 (ITS1) was used. Most of the patients demonstrated dry type single lesions on the head. The results of direct microscopy detection using Giemsastained skin scrapings were compared with that of ITS PCR-RFLP for the diagnosis of cutaneous leishmaniasis. Light microscopy examination showed 37/64 positive cases (58%). PCR revealed 50 positive cases (78%), from which ITS PCR RFLP identified 48 cases (96%) as L. tropica and 2 cases (4%) as L. major. Cutaneous leishmaniasis in Herat appears to be endemic and of the clinically dry type, caused mainly by L. tropica and occasionally by L. major. PMID- 26996361 TI - Impact of a Baby-Friendly hospital on breastfeeding indicators in Shaqlawa district in Erbil governorate, Kurdistan region of Iraq. AB - This study aimed to assess the impact of the Baby-Friendly Hospital Initiative on WHO-defined breastfeeding indicators in Shaqlawa district in Kurdistan region of Iraq. A household survey was carried out on a purposive non-probability sample of 200 mothers with a child aged < 30 months. Mothers were interviewed using a structured form to determine demographic data and feeding practices of the most recent child. The rate of early initiation of breastfeeding was 38.1%, exclusive breastfeeding was 15.4% and continued breastfeeding was 61.0% and 39.5% at 1 and 2 years of age respectively. A significant relationship was found between delivery at the Baby- Friendly accredited hospital and early initiation of breastfeeding but not with exclusive or continued breastfeeding. While continued breastfeeding at 1 year and 2 year was good, early initiation and exclusive breastfeeding indicators were not at an acceptable level, which indicates an ineffective role for the Baby-Friendly Hospital Initiative. PMID- 26996362 TI - Validation of the General Self-Efficacy Scale among Qatari young women. AB - The General Self-Efficacy Scale (GSES) is a measure of people's beliefs about their capacity to cope with life's demands. Self-efficacy may be particularly relevant in transitional stages such as in late adolescence, when young people make decisions that will impact their adult lives. In the present study, we aimed to validate an Arabic version of GSES among 355 Qatari young women aged 18+ years and finishing their final year of high school. We conducted exploratory and confirmatory factor analyses to assess the scale dimensionality. The final model fit was adequate (root mean square error of approximation = 0.07, comparative fit index = 1.00, Tucker-Lewis index = 0.99), confirming a unidimensional self efficacy measure. The Qatari Standard Arabic GSES is a reliable tool for measuring general self-efficacy among young Qatari women. PMID- 26996363 TI - Development and validation of a new tool to measure Iranian pregnant women's empowerment. AB - Empowering pregnant women improves their health and reduces maternal mortality, but there is a lack of suitable tools to measure women's empowerment in some cultures. This study aimed to design and validate a questionnaire for measuring the dimensions of empowerment among Iranian pregnant women. After a literature review, and face and content validity testing, a 38-item questionnaire was developed and tested on a sample of 161 pregnant women. Factor analysis grouped the items into 3 subscales: educational empowerment (e.g. prenatal training), autonomy (e.g. financial independency and mental ability) and sociopolitical empowerment (e.g. involvement in social and political activities). Criterion validity testing showed a strong positive correlation of the total scale and subscales scores with the Kameda and the Spritzer empowerment scales. Cronbach alpha was 0.92 for total empowerment. A total of 32 items remained in the Self Structured Pregnancy Empowerment Questionnaire, which is a valid new tool to measure the dimensions of pregnant women's empowerment. PMID- 26996364 TI - Burnout among physicians and nursing staff working in the emergency hospital of Tanta University, Egypt. AB - Little is known about professional burnout among health-care workers in Egypt. The current study aimed to reveal the extent of burnout among physicians and nursing staff working in the emergency hospital of Tanta University and to identify some of its determinants. A cross-sectional study was carried out on all physicians (n = 266) and a systematic random sample of nurses (n = 284). Burnout was assessed using the Maslach Burnout Inventory and its subscales. Most of the participants (66.0%)had a moderate level of burnout and 24.9% of them had high burnout. Multivariate analysis of variables affecting burnout showed that age, sex, frequency of exposure to work-related violence, years of experience, work burden, supervision and work activities were significant predictors of burnout among the respondents. The authors recommend health education interventions during pre-employment training programmes for prevention of burnout syndrome and periodic screening for early detection and management of burnout. PMID- 26996365 TI - Youth in crisis in the Middle East and North Africa: a systematic literature review and focused landscape analysis. AB - Recent political and demographic factors have exposed the vulnerability of the youth in the Middle East and North Africa (MENA) region. This study aimed to elucidate the current needs, activities, stakeholders and solutions related to at risk youth and young adults in the MENA region. A systematic literature review was conducted of the peer-reviewed and grey literature. This was complemented by an in-region landscape analysis involving key-informant interviews and focus group discussions. After extensive screening of 1160 unique articles, 275 articles were considered relevant to this study. Of these 275, 145 (52.7%) were related to health (64.8% of these related to mental health), 101 (36.7%) to livelihood, 87 (31.6%) to violence prevention and 68 (24.7%) to education. Important themes and challenges identified in the literature and discussions included the MENA region's growing youth bulge; youth unemployment; critical gender gaps; and the impact of conflict on livelihoods, education and health, especially mental health. PMID- 26996366 TI - Nanosized Drug Delivery Systems for Direct Nose to Brain Targeting: A Review. AB - BACKGROUND: Drug targeting to brain has always been problematic due to Blood Brain Barrier (BBB), which, does not allow most of the drugs to pass through it as they are hydrophilic and macromolecular drugs. So, in order to bypass the BBB, alternative modes of administration were searched and nasal to brain delivery route was tried by many workers. Such studies yielded patented nano-formulations with the ability to cross blood brain barrier. METHODS: Nanoparticles being smaller in size and large surface area help in increasing the rate of drug permeation to the brain. In this review work, emphasis has been laid on discussion on various works done in the field of nasal delivery of drugs to brain over the last decade. RESULTS: The works that are discussed in this paper show better drug targeting of brain when given through nasal route as nanoparticles. Experiments performed in animal models have clearly exhibited that nano-sized formulations are able to facilitate the delivery of drugs to brain through nose in comparison to tantamount drug solutions. CONCLUSION: However, it is not yet confirmed whether the drug is freed from the formulation in the nasal cavity and then absorbed or the nanoparticles themselves are absorbed and then the drug is released in the CNS. Furthermore, the toxicity studies were not carried out extensively in suitably designed model, which should be considered before going for further studies and application. PMID- 26996367 TI - Pharmacological Effect of Berberine Chloride in Propyl Thiouracil Induced Thyroidal Dysfunction - A Time Bound Study in Female Rats. AB - BACKGROUND: The present study is aimed at bringing out the information on the effect of berberine chloride in hyper and hypo thyroidal model with two dose levels. OBJECTIVE: The research article also reviewed details of various existing patents associated with comprehensive compilation regarding the therapeutic application of berberine and related forms. METHOD: Sixty female wistar rats weighing between 150-250 gm were divided in to 10 groups. The animals were grouped in to solvent control; hypothyroid; hyperthyroid; prophylactic with two different doses of berberine chloride (50 and 100 mg/kg); treatment groups similar to that of the prophylactic and therapeutic group. To substantiate the dose dependent effect of berberine chloride in 6-n-propyL-2-thiouracil (PTU) induced hypothyroidism, lipid profile, thyroid profile, enzymes profiles and blood profiles, in addition to histopathological studies were also carried out. There was no any significant difference in the lipid profile among solvent control, treatment and prophylactic groups. However, there was a significant difference (***p<0.001) in serum triglycerides, LDL and VLDL of hypothyroid group when compound to that of the rest. RESULTS: As far as thyroid profile is concerned, T3 level of berberine chloride (50 mg/kg) treated groups (prophylactic+ treatment) showed a significant rise compared to hypothyroid group. TSH level in prophylactic groups was far higher than the rest of the groups (3.002+/-0.0192, 1.051+/-0.0008 against the solvent control, 0.308+/ 0.008). SGOT, SGPT levels were significantly higher with the therapeutic group than that of the normal and hypo-thyroidal group. Blood profile of berberine chloride (100 mg/kg) treated therapeutic group was comparable to that of the solvent control than all other groups. The probable mechanism underlying may be that inactivation of type I 5.-iodothyronine deiodinase (5.DI) enzyme by NF-kB pathway. CONCLUSION: From the findings of the current study it can be concluded that berberine chloride possesses both thyroid stimulating and suppressing activities depending on its dose, especially berberine chloride 50 mg/kg supports thyroid stimulating property. PMID- 26996368 TI - Cerebral Metastases in Patients with Left Atrial Myxoma. AB - We describe two cases of cardiac myxomas with cerebral metastases and review the literature on this subject. doi: 10.1111/jocs.12727 (J Card Surg 2016;31:289 293). PMID- 26996369 TI - A Lipid Base Formulation for Intramuscular Administration of a Novel Sulfur Donor for Cyanide Antagonism. AB - This study represents a new formulation of the novel Cyanide (CN) antidote, Dimethyl trisulfide (DMTS), for intramuscular administration. This is a naturally occurring organosulfur molecule with the capability of reacting with CN more efficiently than the present sulfur donor type CN therapy of Thiosulfate (TS). Two types of micelles (PEG2000-DSPE and PEG2000-DSPE/TPGS) were prepared and tested for their ability to encapsulate the liquid, highly lipophilic and volatile drug, DMTS. The micellar encapsulation for DMTS does not only eliminate the possible muscle necrosis at the injection sites, but the rate of evaporation within the micelles is suppressed, that can provide a level of stability for the formulation. The method of micelle preparation was optimized and it was demonstrated that the PEG2000-DSPE preparation can dissolve up to 2.0 mg/ml of the antidote candidate. Keeping the injection volume minimized this could provide a maximum DMTS dose of 12.5 mg/kg. However, even this low dose of DMTS showed a remarkable in vivo therapeutic efficacy (2 X LD50 protection) in a mice model when injected intramuscularly. These in vitro and in vivo findings proved the efficacy of DMTS in combating CN intoxication, and the presented work gives valuable insight to micelle preparation and sets the bases for a more advanced future formulation of DMTS. PMID- 26996371 TI - Piperidine derivatives as nonprostanoid IP receptor agonists. AB - The discovery of a new class of nonprostanoid prostaglandin I2 receptor (IP receptor) agonists is reported. Among them, the unique piperidine derivative 31b (2-((1-(2-(N-(4-tolyl)benzamido)ethyl)piperidin-4-yl)oxy)acetic acid) was a good IP receptor agonist and was 50-fold more selective for the human IP receptor than for other human prostanoid receptors. This compound showed good pharmacokinetic properties in dog. PMID- 26996370 TI - Synthesis, Characterization, and Atenolol Delivery Application of Functionalized Mesoporous Hydroxyapatite Nanoparticles Prepared by Microwave-Assisted Co precipitation Method. AB - BACKGROUND: Atenolol has been used to treat angina and hypertension, either alone or with other antihypertensives. Despite its usefulness, it shows some side effects such as diarrhea and nausea in some patients. A method for slow release of atenolol in intestine is helpful to prevent such side effects. METHODS: A facile co-precipitation microwave-assisted method was used to fabricate mesoporous hydroxyapatite nanoparticles (mHAp). It was then functionalized to have SO3H groups. The synthesized material was used for storage/slow release study of atenolol. RESULTS: Atenolol loaded mHAp shows immediate release of atenolol in pH 8, whileafter functionalizing shows up to ca. 30% release at the beginning. In pH 1, 50% of drug was released after 10 h from AT@mHAp and after 18h the drug was almost completely released.The drug release profiles of functionalized HAp at pH value 1 and 8reveals the complete release of atenolol in intestine pH, while no complete release is observed in stomach environment. CONCLUSION: The aims of this work were synthesis and characterization of mesoporous HAp through the microwave-assisted co-precipitation method and elucidate the underlying drug release capability of mesoporous HAp nanoparticles. The SO3H group was incorporated into the mesoporous HAp and then used as drug delivery carriers using atenolol as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). Increasing pH value to 8 causes increase in the drug release. PMID- 26996372 TI - Identification of new quinic acid derivatives as histone deacetylase inhibitors by fluorescence-based cellular assay. AB - A fluorescence-based cellular assay system was established to identify potential epigenetic modulator ligands. This assay method is to detect the de-repression of an EGFP reporter in cancer cells by the treatment of HDAC (histone deacetylase) or DNMT (DNA methyltransferase) inhibitor. Using this system, we conducted a preliminary screening of in-house natural product library containing extracts and pure compounds, and identified several active compounds. Among them, novel quinic acid derivatives were recognized as excellent HDAC inhibitors by both enzymatic and cell-based HDAC assays. PMID- 26996373 TI - Synthesis of azepino[4,5-b]indol-4-ones via MCR/free radical cyclization and in vitro-in silico studies as 5-Ht6R ligands. AB - A series of nine new 3-acetamide-azepino[4,5-b]indol-4-ones were synthesized in two steps: (i) multicomponent reaction (Ugi-4CR/SN2) and (ii) free radical mediated cyclization. These compounds, along with their tetrazole-based analogs, were studied in vitro to assess their binding with the 5-hydroxytryptamine type 6 receptor (5-Ht6R). The 3-acetamide-azepino[4,5-b]indol-4-ones displayed moderate affinity, whereas the 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones affinity values are lower. However, one of the 3-acetamide-azepino[4,5-b]indol-4-ones exhibited a hit value of Ki (211.2nM) to the 5-Ht6R. Minimal-energy structures of one cis-amide and its tetrazole-based analog (calculated by means of the Density Functional Theory) were analyzed to assess some interesting bioisosterism aspects. Interactions and binding energies between all products and the 5-Ht6R were calculated through in silico molecular couplings. Finally, a QSAR model was proposed using the results of the in vitro assays. PMID- 26996374 TI - Discovery of a series of 8-(2,3-dihydro-1,4-benzoxazin-4-ylmethyl)-2-morpholino-4 oxo-chromene-6-carboxamides as PI3Kbeta/delta inhibitors for the treatment of PTEN-deficient tumours. AB - We report the discovery and optimisation of a series of 8-(2,3-dihydro-1,4 benzoxazin-4-ylmethyl)-2-morpholino-4-oxo-chromene-6-carboxamides, leading to compound 16 as a potent and selective PI3Kbeta/delta inhibitor: PI3Kbeta cell IC50 0.012 MUM (in PTEN null MDA-MB-468 cell) and PI3Kdelta cell IC50 0.047 MUM (in Jeko-1 B-cell), with good pharmacokinetics and physical properties. In vivo, 16 showed profound pharmacodynamic modulation of AKT phosphorylation in a mouse PTEN-deficient PC3 prostate tumour xenograft after a single oral dose and gave excellent tumour growth inhibition in the same model after chronic oral dosing. Compound 16 was selected as a preclinical candidate for the treatment of PTEN deficient tumours. PMID- 26996375 TI - Deficiency of prolyl oligopeptidase in mice disturbs synaptic plasticity and reduces anxiety-like behaviour, body weight, and brain volume. AB - Prolyl oligopeptidase (PREP) has been implicated in neurodegeneration and neuroinflammation and has been considered a drug target to enhance memory in dementia. However, the true physiological role of PREP is not yet understood. In this paper, we report the phenotyping of a mouse line where the PREP gene has been knocked out. This work indicates that the lack of PREP in mice causes reduced anxiety but also hyperactivity. The cortical volumes of PREP knockout mice were smaller than those of wild type littermates. Additionally, we found increased expression of diazepam binding inhibitor protein in the cortex and of the somatostatin receptor-2 in the hippocampus of PREP knockout mice. Furthermore, immunohistochemistry and tail suspension test revealed lack of response of PREP knockout mice to lipopolysaccharide insult. Further analysis revealed significantly increased levels of polysialylated-neural cell adhesion molecule in PREP deficient mice. These findings might be explained as possible alteration in brain plasticity caused by PREP deficiency, which in turn affect behaviour and brain development. PMID- 26996376 TI - Synergy between tobramycin and trivalent chromium ion in electrochemical control of Pseudomonas aeruginosa. AB - We recently demonstrated that the effectiveness of tobramycin (Tob), an aminoglycoside, against antibiotic-tolerant persister cells of Pseudomonas aeruginosa can be enhanced by electrochemical factors generated from direct currents (DC). Supplementation of Ni(II), Cr(III) and Fe(II) during carbon mediated DC treatment revealed that these metal cations promote killing of persister cells in the presence of tobramycin, which led to our hypothesis that specific interactions between Tob and some metal ions contribute to the synergistic killing of persister cells. In this study, the interactions between selected metal cations and Tob were investigated using (1)H-(13)C HSQC NMR. Increase in the concentration of Cr(III) (in the form of [CrCl2(H2O)4](+)) in solutions containing Tob was found to shift the HSQC NMR peaks of Tob to new positions, suggesting the formation of a Cr(III)-Tob complex. Crystal field effects and electrochemical properties of the complex were further studied using UV-visible spectroscopy and cyclic voltammetry, which led to the finding that the Cr(III)-Tob complex has increased affinity with negatively charged nucleic acids. These findings are helpful for understanding the mechanism of electrochemical control of bacterial cells and for developing more effective antimicrobial therapies based on aminoglycosides and electrochemical species released from various metallic biomaterials. STATEMENT OF SIGNIFICANCE: Medical device associated infections present a major challenge to healthcare and the quality of life of affected individuals. This problem is further exacerbated by the emergence of multidrug resistant pathogens. Thus, alternative methods for microbial control are urgently needed. Recently, we reported synergy between tobramycin and low-level electrochemical currents generated using stainless steel electrodes in killing bacterial persister cells, a dormant population with high level intrinsic tolerance to antibiotics. In this article, we describe how electrically-induced interaction between aminoglycosides and certain metal cations enhance the potency of tobramycin in bacterial killing. The findings will help design new methods for controlling infections through electrochemical disruption of cellular function and associated drug resistance. PMID- 26996377 TI - Thermally triggered injectable hydrogel, which induces mesenchymal stem cell differentiation to nucleus pulposus cells: Potential for regeneration of the intervertebral disc. AB - There is an urgent need for new therapeutic options for low back pain, which target degeneration of the intervertebral disc (IVD). Here, we investigated a pNIPAM hydrogel system, which is liquid at 39 degrees C ex vivo, where following injection into the IVD, body temperature triggers gelation. The combined effects of hypoxia (5% O2) and the structural environment of the hydrogel delivery system on the differentiation of human mesenchymal stem cells (hMSCs), towards an NP cell phenotype was investigated. hMSCs were incorporated into the liquid hydrogel, the mixture solidified and cultured for up to 6weeks under 21% O2 or 5% O2 where viability was maintained. Immunohistochemistry revealed significant increases in NP matrix components: aggrecan; collagen type II and chondroitin sulphate after culture for 1week in 5% O2, accompanied by increased matrix staining for proteoglycans and collagen, observed histologically. NP markers HIF1alpha, PAX1 and FOXF1 were also significantly increased where hMSC were incorporated into hydrogels with accelerated expression observed when cultured in 5% O2. hMSCs cultured under hypoxic conditions, which mimic the native disc microenvironment, accelerate differentiation of hMSCs within the hydrogel system, towards the NP phenotype without the need for chondrogenic inducing medium or additional growth factors, thus simplifying the treatment strategy for the repair of IVD degeneration. PMID- 26996378 TI - Ileal endometriosis and Crohn's disease: an unusual association causing acute bowel obstruction. AB - AIM: Endometriosis is a commun health disorder in women, which is defined as the presence of bowel endometrial-like tissue outside the uterus. Bowel endometriosis occurs in approximately10% pf all cases, with ileal localization as a very rare clinical intestinal occlusion:acute intestinal obstruction is possible presentation of this disease. We report a case of a patient with known history of Crohn's treated with ileal resection for acute intestinal occlusion;histology showed the coexistence of IBD and endometriosis in the intestinal wall. CASE REPORT: A 35 years old female patient, with previous diagnosis of Crohn's disease confirmed by endoscopic biopsies, was admitted to our Institutions because oc acute intestinal obstruction. She previously suffered of dysmenorrhea and pelvic pain during menstration. A contrast enhanced CT abdominal scan was performed with evidence of diffuse small bowel fluid distension and thickening of terminal iileum wall, compatible with ilea stenosis in acute Crohn disease. RESULTS: The patient underwent laparoscopic resection of distal ileus. Definitive histological examination showed ileal wall with multiple endometriosis foci and chronic follicular flogosis. CONCLUSION: The case that we have described shows a rare co existence of the two clinical entitle (Crohn's disease and ileal deep endometriosis), histologically demonstrated, with acute presentation as intestinal obstruction, susseflully treated with laparoscopic ileal resection KEY WORDS Bowel obstruction, Crohn's disease, Endometriosis. PMID- 26996380 TI - Is blood donation an opportunity for hypertension awareness? AB - OBJECTIVES: To assess the blood pressure (BP) of donors, the rate of hypertensive range readings amongst donors not previously identified as hypertensive and determine the value of an informational sheet about hypertension given at the time of donation. AIM: To determine the value of screening for high BP during blood donation as a public health activity. BACKGROUND: Blood donation centres measure donor BPs before accepting donations and thus provide a unique opportunity for hypertension screening and education. MATERIALS/METHODS: An anonymous survey was completed by blood donors over 2 weeks. The survey contained 22 questions regarding demographics, BP knowledge and monitoring. Participants then received a hypertension information sheet and assessed its utility with three additional questions. RESULTS: Out of 839 survey responses received, 688 respondents reported their BP in the following categories, normotensive range: 46.9%, pre-hypertensive range: 41.7% and hypertensive range: 11.3%. Notably, of donors with hypertensive range readings, 45% reported no known history of hypertension. After reading the hypertension pamphlet, 63.9% of donors found it valuable, while 38.9% did not. Furthermore, 67% of donors said they were likely to use the information they learned, while 23% of donors said they were unlikely to do so. CONCLUSIONS: An opportunity exists for increasing hypertension awareness during blood donation. Additionally, our findings indicate that an educational pamphlet at the time of donation is valuable to donors. Overall, these findings suggest that increasing hypertension awareness as part of a blood donation screening is not only needed but also useful as a public health measure. PMID- 26996379 TI - Glutathione biosynthesis is upregulated at the initiation of MYCN-driven neuroblastoma tumorigenesis. AB - The MYCN gene is amplified and overexpressed in a large proportion of high stage neuroblastoma patients and has been identified as a key driver of tumorigenesis. However, the mechanism by which MYCN promotes tumor initiation is poorly understood. Here we conducted metabolic profiling of pre-malignant sympathetic ganglia and tumors derived from the TH-MYCN mouse model of neuroblastoma, compared to non-malignant ganglia from wildtype littermates. We found that metabolites involved in the biosynthesis of glutathione, the most abundant cellular antioxidant, were the most significantly upregulated metabolic pathway at tumor initiation, and progressively increased to meet the demands of tumorigenesis. A corresponding increase in the expression of genes involved in ribosomal biogenesis suggested that MYCN-driven transactivation of the protein biosynthetic machinery generated the necessary substrates to drive glutathione biosynthesis. Pre-malignant sympathetic ganglia from TH-MYCN mice had higher antioxidant capacity and required glutathione upregulation for cell survival, when compared to wildtype ganglia. Moreover, in vivo administration of inhibitors of glutathione biosynthesis significantly delayed tumorigenesis when administered prophylactically and potentiated the anticancer activity of cytotoxic chemotherapy against established tumors. Together these results identify enhanced glutathione biosynthesis as a selective metabolic adaptation required for initiation of MYCN-driven neuroblastoma, and suggest that glutathione-targeted agents may be used as a potential preventative strategy, or as an adjuvant to existing chemotherapies in established disease. PMID- 26996382 TI - A cell-free framework for rapid biosynthetic pathway prototyping and enzyme discovery. AB - Speeding up design-build-test (DBT) cycles is a fundamental challenge facing biochemical engineering. To address this challenge, we report a new cell-free protein synthesis driven metabolic engineering (CFPS-ME) framework for rapid biosynthetic pathway prototyping. In our framework, cell-free cocktails for synthesizing target small molecules are assembled in a mix-and-match fashion from crude cell lysates either containing selectively enriched pathway enzymes from heterologous overexpression or directly producing pathway enzymes in lysates by CFPS. As a model, we apply our approach to n-butanol biosynthesis showing that Escherichia coli lysates support a highly active 17-step CoA-dependent n-butanol pathway in vitro. The elevated degree of flexibility in the cell-free environment allows us to manipulate physiochemical conditions, access enzymatic nodes, discover new enzymes, and prototype enzyme sets with linear DNA templates to study pathway performance. We anticipate that CFPS-ME will facilitate efforts to define, manipulate, and understand metabolic pathways for accelerated DBT cycles without the need to reengineer organisms. PMID- 26996381 TI - Engineering Escherichia coli for the synthesis of short- and medium-chain alpha,beta-unsaturated carboxylic acids. AB - Concerns over sustained availability of fossil resources along with environmental impact of their use have stimulated the development of alternative methods for fuel and chemical production from renewable resources. In this work, we present a new approach to produce alpha,beta-unsaturated carboxylic acids (alpha,beta-UCAs) using an engineered reversal of the beta-oxidation (r-BOX) cycle. To increase the availability of both acyl-CoAs and enoyl-CoAs for alpha,beta-UCA production, we use an engineered Escherichia coli strain devoid of mixed-acid fermentation pathways and known thioesterases. Core genes for r-BOX such as thiolase, hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and enoyl-CoA reductase were chromosomally overexpressed under the control of a cumate inducible phage promoter. Native E. coli thioesterase YdiI was used as the cycle-terminating enzyme, as it was found to have not only the ability to convert trans-enoyl-CoAs to the corresponding alpha,beta-UCAs, but also a very low catalytic efficiency on acetyl-CoA, the primer and extender unit for the r-BOX pathway. Coupling of r-BOX with YdiI led to crotonic acid production at titers reaching 1.5g/L in flask cultures and 3.2g/L in a controlled bioreactor. The engineered r-BOX pathway was also used to achieve for the first time the production of 2-hexenoic acid, 2 octenoic acid, and 2-decenoic acid at a final titer of 0.2g/L. The superior nature of the engineered pathway was further validated through the use of in silico metabolic flux analysis, which showed the ability of r-BOX to support growth-coupled production of alpha,beta-UCAs with a higher ATP efficiency than the widely used fatty acid biosynthesis pathway. Taken together, our findings suggest that r-BOX could be an ideal platform to implement the biological production of alpha,beta-UCAs. PMID- 26996383 TI - The association between non-alcoholic steatohepatitis and intrahepatic cholangiocarcinoma: A hospital based case-control study. AB - BACKGROUND: This study aimed to investigate the association between non-alcoholic steatohepatitis (NASH) and intrahepatic cholangiocarcinoma (ICC). METHODS: This was a case control study of patients who underwent surgical resection either for ICC or for a metastatic liver tumor (the control group). We assessed their clinical characteristics, pathological findings, and the prevalence of known ICC risk factors. For patients without known risk factors, we compared other factors including the prevalence of NASH. RESULTS: In the patients without known risk factors, 15 of 34 patients in the ICC group and 13 of 69 patients in the control group were diagnosed with NASH. Univariate analysis showed significantly higher values in the ICC group for age (P = 0.0478), prevalence of obesity (P = 0.0365) and NASH (P = 0.0078), and serum levels of albumin (P = 0.0051), and gamma glutamyl transpeptidase (gamma-GTP) (P = 0.0006) compared with the control group. Multivariate analysis showed that age and serum levels of gamma-GTP and NASH were independent risk factors for ICC. In patients with NASH, the proportion of patients with hepatic fibrosis was significantly higher in the ICC group than in the control group (P = 0.0014). CONCLUSION: NASH is a possible risk factor for ICC development. J. Surg. Oncol. 2016;113:779-783. (c) 2016 Wiley Periodicals, Inc. PMID- 26996384 TI - Application of a standardised protocol for hepatic venous pressure gradient measurement improves quality of readings and facilitates reduction of variceal bleeding in cirrhotics. AB - INTRODUCTION: Hepatic venous pressure gradient (HVPG) measurement is recommended for prognostic and therapeutic indications in centres with adequate resources and expertise. Our study aimed to evaluate the quality of HVPG measurements at our centre before and after introduction of a standardised protocol, and the clinical relevance of the HVPG to variceal bleeding in cirrhotics. METHODS: HVPG measurements performed at Singapore General Hospital from 2005-2013 were retrospectively reviewed. Criteria for quality HVPG readings were triplicate readings, absence of negative pressure values and variability of <= 2 mmHg. The rate of variceal bleeding was compared in cirrhotics who achieved a HVPG response to pharmacotherapy (reduction of the HVPG to < 12 mmHg or by >= 20% of baseline) and those who did not. RESULTS: 126 HVPG measurements were performed in 105 patients (mean age 54.7 +/- 11.4 years; 55.2% men). 80% had liver cirrhosis and 20% had non-cirrhotic portal hypertension (NCPH). The mean overall HVPG was 13.5 +/- 7.2 mmHg, with a significant difference between the cirrhosis and NCPH groups (p < 0.001). The proportion of quality readings significantly improved after the protocol was introduced. HVPG response was achieved in 28 (33.3%, n = 84) cirrhotics. Nine had variceal bleeding over a median follow-up of 29 months. The rate of variceal bleeding was significantly lower in HVPG responders compared to nonresponders (p = 0.025). CONCLUSION: The quality of HVPG measurements in our centre improved after the introduction of a standardised protocol. A HVPG response can prognosticate the risk of variceal bleeding in cirrhotics. PMID- 26996385 TI - Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple negative breast cancer. AB - Background In tumors carrying BRCA mutations, DNA damage caused by standard cytotoxic chemotherapy can be potentiated by poly [ADP-ribose] polymerase (PARP) inhibitors, leading to increased cell death through synthetic lethality. Individuals carrying mutations in BRCA have an increased incidence of triple negative breast cancer (TNBC). In order to assess the role of PARP inhibition in the treatment of TNBC, we conducted a randomized phase II trial of the combination of veliparib, a small molecule PARP inhibitor, with the cytotoxic agent cyclophosphamide versus cyclophosphamide alone in patients with refractory TNBC. Methods Adult patients with TNBC were randomized to receive oral cyclophosphamide 50 mg once daily with or without oral veliparib at 60 mg daily in 21-day cycles. Patients on the cyclophosphamide arm could crossover to the combination arm at disease progression. Results Forty-five patients were enrolled; 18 received cyclophosphamide alone and 21 received the combination as their initial treatment regimen. Lymphopenia was the most common grade 3/4 toxicity noted in both arms. One patient in the cyclophosphamide alone arm, and 2 in the combination arm had objective responses. Response rates and median progression free survival did not significantly differ between both treatment arms. Conclusion The addition of veliparib to cyclophosphamide, at the dose and schedule evaluated, did not improve the response rate over cyclophosphamide treatment alone in patients with heavily pre-treated triple-negative breast cancer. PMID- 26996386 TI - Meta-Analysis of Gene Expression Patterns in Animal Models of Prenatal Alcohol Exposure Suggests Role for Protein Synthesis Inhibition and Chromatin Remodeling. AB - BACKGROUND: Prenatal alcohol exposure (PAE) can result in an array of morphological, behavioral, and neurobiological deficits that can range in their severity. Despite extensive research in the field and a significant progress made, especially in understanding the range of possible malformations and neurobehavioral abnormalities, the molecular mechanisms of alcohol responses in development are still not well understood. There have been multiple transcriptomic studies looking at the changes in gene expression after PAE in animal models; however, there is a limited apparent consensus among the reported findings. In an effort to address this issue, we performed a comprehensive re analysis and meta-analysis of all suitable, publically available expression data sets. METHODS: We assembled 10 microarray data sets of gene expression after PAE in mouse and rat models consisting of samples from a total of 63 ethanol (EtOH) exposed and 80 control animals. We re-analyzed each data set for differential expression and then used the results to perform meta-analyses considering all data sets together or grouping them by time or duration of exposure (pre- and postnatal, acute and chronic, respectively). We performed network and Gene Ontology enrichment analysis to further characterize the identified signatures. RESULTS: For each subanalysis, we identified signatures of differential expressed genes that show support from multiple studies. Overall, the changes in gene expression were more extensive after acute EtOH treatment during prenatal development than in other models. Considering the analysis of all the data together, we identified a robust core signature of 104 genes down-regulated after PAE, with no up-regulated genes. Functional analysis reveals over representation of genes involved in protein synthesis, mRNA splicing, and chromatin organization. CONCLUSIONS: Our meta-analysis shows that existing studies, despite superficial dissimilarity in findings, share features that allow us to identify a common core signature set of transcriptome changes in PAE. This is an important step to identifying the biological processes that underlie the etiology of fetal alcohol spectrum disorders. PMID- 26996388 TI - Monsters, dreams and madness: Commentary on 'The arms of the chimeras'. AB - Considering Freudian and Post-Freudian approaches to the intersubjective Beatrice Ithier puts the work of Michel de M'Uzan and Thomas Ogden in comparison. To this comparison I add a consideration of the work of Christopher Bollas. The highly creative clinical approaches these three theorists take is shown to be informed by their elaborations of the Freudian notion of unconscious communication and by new approaches to the issue of identity. Attention is paid to differentiating traumatic from fanciful chimeras; and to the experience of the analyst undergoing the sorts of transformations requisite to entering this psychic space marked by fluid exchanges of being and becoming, wherein analyst becomes patient, new subjects are created through shared dreams, and through which monsters appear. PMID- 26996387 TI - On-line visual control of grasping movements. AB - Even though it is recognized that vision plays an important role in grasping movements, it is not yet fully understood how the visual feedback of the hand contributes to the on-line control. Visual feedback could be used to shape the posture of the hand and fingers, to adjust the trajectory of the moving hand, or a combination of both. Here, we used a dynamic perturbation method that altered the position of the visual feedback relative to the actual position of the thumb and index finger to virtually increase or decrease the visually sensed grip aperture. Subjects grasped objects in a virtual 3D environment with haptic feedback and with visual feedback provided by small virtual spheres anchored to the their unseen fingertips. We found that the effects of the visually perturbed grip aperture arose preeminently late in the movement when the hand was in the object's proximity. The on-line visual feedback assisted both the scaling of the grip aperture to properly conform it to the object's dimension and the transport of the hand to correctly position the digits on the object's surface. However, the extent of these compensatory adjustments was contingent on the viewing geometry. The visual control of the actual grip aperture was mainly observed when the final grasp axis orientation was approximately perpendicular to the viewing direction. On the contrary, when the final grasp axis was aligned with the viewing direction, the visual control was predominantly concerned with the guidance of the digit toward the visible final contact point. PMID- 26996389 TI - Role of testosterone in regulating induction of TNF-alpha in rat spleen via ERK signaling pathway. AB - Spleen is a pivotal organ for regulating immune homeostasis. It has been shown that testosterone diminishes secretion of various inflammatory molecules under multiple conditions. However, the mechanisms of action of endogenous testosterone affecting immune responses in the spleen remain unknown. The aim of the present study was to evaluate the immune functions of the spleen in response to testosterone withdrawal after orchidectomy, and the impact of splenocytes on the bacterial endotoxin lipopolysaccharide (LPS)-induced secretion of inflammatory molecules. Male rats were divided into 3 groups, i.e. intact, orchidectomized (Orch) and orchidectomized plus replacement of testosterone propionate (TP) (Orch+TP). The Orch and Orch+TP rats underwent bilateral orchidectomy one week before TP replacement (2mg/kg body weight) or sesame oil in intact rats as controls for seven days. Orch resulted in a significant increase of spleen weight and basal secretion of nitric oxide (NO) from splenocytes. Additionally, LPS up regulated cell proliferation and the secretion of tumor necrosis factor-alpha (TNF-alpha) in splenocytes of Orch rats. Orch further up-regulated phosphorylation of extracellular signal-regulated kinases. Interestingly, the plasma corticosterone concentration in the Orch group was higher than that in the intact and Orch+TP groups. Deficiency of testosterone-elevated TNF-alpha and NO secretion in response to LPS were confirmed in the rat splenocytes. Testosterone also significantly attenuated LPS-elicited release of TNF-alpha and NO in a dose dependent manner. However, testosterone did not suppress splenic blastogenesis at doses in the 10(-10)-10(-7)M concentration range. In this context, testosterone might have a protective role against inflammatory responses in the spleen. The present study provides evidence to indicate that testosterone might modulate the immune system. PMID- 26996391 TI - One-hour post-load plasma glucose level during the OGTT predicts mortality: observations from the Israel Study of Glucose Intolerance, Obesity and Hypertension. AB - AIMS: The relationship between 1- and 2-h glucose levels following an oral glucose tolerance test (OGTT) and long-term mortality was evaluated. METHODS: Over a 33-year period, 2138 individuals were followed for all-cause mortality. Fasting and post-OGTT glucose parameters categorized the cohort according to baseline glycaemic status. Four categories were established according to 1- and 2 h glucose levels (in mmol/l): group A = 1 h <= 8.8 and 2 h < 7.8; group B = 1 h > 8.6 and 2 h < 7.8; group C = 1 h <= 8.6 and 2 h = 7.8-11.1 (impaired glucose tolerance); group D = 1 h > 8.6 and 2 h = 7.8-11.1 (impaired glucose tolerance). Individuals with diabetes at baseline were excluded from the cohort. RESULTS: By August 2013, 51% of the study cohort had died. The worst prognosis occurred in group D (73.8% mortality), followed by groups C (67.5%), B and A (57.9% and 41.6%, respectively). When the 2-h glucose value is 'normal' (< 7.8 mmol/l), the 1-h glucose value > 8.6 mmol/l is an important predictor of mortality (28% increased risk) compared with group A, controlling for sex, age, smoking, BMI, systolic and diastolic blood pressures. A gradual increased hazard for mortality was seen by study group (hazard ratio = 1.28, 1.60 and 1.76, for groups B, C and D, respectively; group A = reference). CONCLUSIONS: A 1-h glucose value > 8.6 mmol/l predicts mortality even when the 2-h level is < 7.8 mmol/l. However, when the 2-h level is in the impaired glucose tolerance range, the hazard for mortality rises significantly independent of the 1-h value. Individuals at risk for developing diabetes could be identified earlier using the 1-h threshold value of 8.6 mmol/l, which could avert progression to diabetes and increased mortality.?. PMID- 26996390 TI - Effects of acrolein on the production of corticosterone in male rats. AB - Acrolein, an alpha, beta-unsaturated aldehyde, exists in a wide range of sources. Acrolein can be not only generated from all types of smoke but also produced endogenously from the metabolism by lipid peroxidation. The cellular influence of acrolein is due to its electrophilic character via binding to and depleting cellular nucleophiles. Although the toxicity of acrolein has been extensively studied, there is relatively little information about its impact on hormone release. This study aimed at the effect of acrolein on hypothalamic-pituitary adrenal (H-P-A) axis. In an in vivo study, male rats were administrated with acrolein for 1 or 3days. The plasma corticosterone in response to a single injection of adrenocorticotropic hormone (ACTH) increased slowly in acrolein pretreated rats than in control rats. Further investigating the steroidogenic pathway, the protein expressions of steroidogenic acute regulatory protein (StAR) and the upper receptor-melanocortin 2 receptor (MC2R) were attenuated in acrolein treated groups. Another experiment using trilostane showed less activity of P450scc in zona fasciculata-reticularis (ZFR) cells in acrolein-treated groups. In addition to the suppressed ability of corticosterone production in ZFR cells, acrolein even had extended influence at higher concentrations. The lower ACTH was observed in the plasma from acrolein-pretreated rats. In an in vitro study, ZFR cells were incubated with acrolein and the results showed that corticosterone concentrations in media were decreased in a dose-dependent manner. Acrolein also desensitized the response of the ZFR cells to ACTH. These results suggested that acrolein decreased the releasing ability of corticosterone via an inhibition on the response of ZFR cells to ACTH and the reduction of protein expressions of StAR and MC2R as well as the activity of P450scc in rat ZFR cells. The present evidences showed that the H-P-A axis was affected by the administration of acrolein. PMID- 26996392 TI - Prediction and validation of association between microRNAs and diseases by multipath methods. AB - BACKGROUND: Deciphering the genetic basis of human diseases is an important goal in biomedical research. There is increasing evidence suggesting that microRNAs play critical roles in many key biological processes. So the identification of microRNAs associated with disease is very important for understanding the pathogenesis of diseases. METHODS: Two multipath methods are introduced to predict the associations between microRNAs and diseases based on microRNA-disease heterogeneous network. The first method, HeteSim_MultiPath (HSMP), uses the HeteSim measure to calculate the similarity between objects and combines the HeteSim scores of different paths with a constant that dampens the contributions of longer paths. The second one, HeteSim_SVM (HSSVM), uses the HeteSim measure and the machine learning method used to combine HeteSim scores instead of a constant. RESULTS: We use the leave-one-out cross-validation to evaluate our novel methods, and find that our methods are better than other methods. We achieve an area under the ROC curve of 0.981 and 0.984 respectively. We also check the top-10 most similarity of microRNAs-diseases associations and find that our predictions are reasonable and credible. CONCLUSIONS: The encouraging results suggest that multipath methods can provide help in identifying novel microRNA disease associations, and guide biological experiments for scientific research. This article is part of a Special Issue entitled "System Genetics". Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. PMID- 26996393 TI - DDAH1 plays dual roles in PM2.5 induced cell death in A549 cells. AB - BACKGROUND: Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an enzyme that can degrade asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor. Emerging evidence suggests that alterations in the ADMA DDAH1 pathway are involved in environmental pollution induced airway inflammation. However, the role of DDAH1 in protection against cytotoxicity of ambient airborne particulate matter is unclear. METHODS: We examined the influence of DDAH1 expression on oxidative stress and cell apoptosis in human type II alveolar epithelial A549 cells exposed to PM2.5 (particulate matter with an aerodynamic diameter less than 2.5MUM). RESULTS: We found that PM2.5 exposure for 48h significantly decreased DDAH1 expression. However, knockdown of DDAH1 prior to PM2.5 exposure actually attenuated the cytotoxicity of PM2.5. Cytoprotection in DDAH1 deficient cells was due to increased reactive oxygen species, activation of PI3K-AKT and mitogen-activated protein kinase (MAPK) pathways, subsequent activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and this caused a subsequent reduction in PM2.5 induced oxidative stress relative to control. DDAH1 depletion also repressed the induction of inducible NOS (iNOS) in PM2.5-exposed cells and knockdown of iNOS protected cells against PM2.5 induced cell death. Interestingly, overexpression of DDAH1 also exerted a protective effect against the cytotoxicity of PM2.5 and this was associated with a reduction in oxidative stress and upregulation of the anti-apoptotic protein Bcl-2. CONCLUSIONS: Our data indicate that DDAH1 plays dual roles in protection against cytotoxicity of PM2.5 exposure, apparently by limiting PM2.5 induced oxidative stress. GENERAL SIGNIFICANCE: Our findings reveal new insights into the role(s) of the DDAH1/ADMA in pulmonary protection against airborne pollutants. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. PMID- 26996394 TI - Analysis of major elements in pigmented melanocytic chicken skin using laser induced breakdown spectroscopy. AB - The concentration difference of major elements in melanocytic skin with respect to pigmentation level is analysed by laser-induced breakdown spectroscopy (LIBS) to investigate the applicability of LIBS as an in situ feedback tool for selective and complete laser removal of melanocytic skin tissue like nevus. The skin of black silkie chicken which had a characteristic darkly pigmented perifollicular skin surrounded by lightly pigmented extrafollicular skin was used as the sample. The results showed higher LIBS signal intensities of Ca2+ and Mg2+ but lower intensities of Na+ , Cl- and K+ in the perifollicular skin than in the extrafollicular skin, which demonstrated the feasibility to use LIBS as a reliable method to distinguish skin tissues with difference in pigmentation level. Plasma emission of biochemical elements generated with a laser irradiation on melanocytic skin lesion. PMID- 26996395 TI - Peripheral blood late mixed chimerism in leucocyte subpopulations following allogeneic stem cell transplantation for childhood malignancies: does it matter? AB - The impact of persistent mixed chimerism (MC) after haematopoietic stem cell transplantation (HSCT) remains unclarified. We investigated the incidence of MC in peripheral blood beyond day +50 after HSCT and its impact on rejection, chronic graft-versus-host disease (c-GvHD) and relapse in 161 children receiving allogeneic HSCT for haematological malignancies. The 1-year incidence of late MC was 26%. Spontaneous conversion to complete donor chimerism (CC) occurred in 43% of patients as compared to 62% after donor lymphocyte infusions. No graft rejection occurred. The 1-year incidence of c-GvHD was 20 +/- 7% for MC, and 18 +/- 4% for CC patients (P = 0.734). The 3-year cumulative incidence of relapse (CIR) according to chimerism status at days +50 and +100 was 22 +/- 4% for CC patients vs. 22 +/- 8% for MC patients (day +50; P = 0.935) and 21 +/- 4% vs. 20 +/- 7% (day +100; P = 0.907). Three-year CIRs in patients with persistent MC and patients with CC/limited MC were comparable (8 +/- 7% vs. 19 +/- 4%; P = 0.960). HSCT for acute leukaemia or myelodysplastic syndrome as secondary malignancies (hazard ratio (HR) 4.7; P = 0.008), for AML (HR 3.0; P = 0.02) and from mismatched donors (HR 3.1; P = 0.03) were independent factors associated with relapse. Our data suggest that late MC neither protects from c-GvHD nor does it reliably predict impending disease relapse. PMID- 26996396 TI - Evaluating facility-based antiretroviral therapy programme effectiveness: a pilot study comparing viral load suppression and retention rates. AB - OBJECTIVES: Increased demand for antiretroviral therapy (ART) services combined with plateaued levels of development assistance for HIV/AIDS requires that national ART programmes monitor programme effectiveness. In this pilot study, we compared commonly utilised performance metrics of 12- and 24-month retention with rates of viral load (VL) suppression at 15 health facilities in Uganda. METHODS: Retrospective chart review from which 12- and 24-month retention rates were estimated, and parallel HIV RNA VL testing on consecutive adult patients who presented to clinics and had been on ART for a minimum of six months. Rates of VL suppression were then calculated at each facility and compared to retention rates to assess the correlation between performance metrics. Multilevel logistic regression models predicting VL suppression and 12- and 24-month retention were constructed to estimate facility effects. RESULTS: We collected VL samples from 2961 patients and found that 88% had a VL <=1000 copies/ml. Facility rates of VL suppression varied between 77% and 96%. When controlling for patient mix, a significant variation in facility performance persisted. Retention rates at 12 and 24 months were 91% and 79%, respectively, with a comparable facility-level variation. However, neither 12-month (rho = 0.16) nor 24-month (rho = -0.19) retention rates were correlated with facility rates of VL suppression. CONCLUSIONS: Retaining patients in care and suppressing VL are both critical outcomes. Given the lack of correlation noted in this study, the utilisation of VL monitoring may be necessary to truly assess the effectiveness of health facilities delivering ART services. PMID- 26996397 TI - Preparation and characterization of chitosan-Polyethylene glycol polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles as carrier system: Drug loading and in vitro drug release study. AB - In the present research work, the anticancer drug "curcumin" is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe3 O4 ) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Curcumin drug loaded Fe3 O4 -CS, Fe3 O4 -CS- PEG and Fe3 O4 -CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183 - 390 nm with a zeta potential value of 26 mV-41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behaviour of curcumin drug-loaded Fe3 O4 -CS, Fe3 O4 -CS-PEG, and Fe3 O4 -CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium (4.5 and 7.4) and temperature (37 degrees C and 45 degrees C), and it was proved that the drug release depends upon the pH medium and temperature in addition to the nature of matrix. PMID- 26996399 TI - Emergency response in a global health crisis: epidemiology, ethics, and Ebola application. AB - PURPOSE: The link between ethics and epidemiology can go unnoticed in contemporary gatherings of professional epidemiologists or trainees at conferences and workshops, as well as in teaching. Our goal is to provide readers with information about the activities of the College and to provide a broad perspective on a recent major issue in epidemiology. METHODS: The Ethics Committee of the American College of Epidemiology (ACE) presented a plenary session at the 2015 Annual Meeting in Atlanta, GA, on the complexities of ethics and epidemiology in the context of the 2014-2015 Ebola virus disease outbreak and response in West Africa. This article presents a summary and further discussion of that plenary session. RESULTS: Three main topic areas were presented: clinical trials and ethics in public health emergencies, public health practice, and collaborative work. A number of key ethical concepts were highlighted and discussed in relation to Ebola and the ACE Ethics Guidelines. CONCLUSIONS: The Ebola virus disease outbreak is an example of a public health humanitarian crisis from which we hope to better understand the role of professional epidemiologists in public health practice and research and recognize ethical challenges epidemiologists faced. PMID- 26996398 TI - A Highly Sensitive Diketopyrrolopyrrole-Based Ambipolar Transistor for Selective Detection and Discrimination of Xylene Isomers. AB - An ambipolar poly(diketopyrrolopyrrole-terthiophene)-based field-effect transistor (FET) sensitively detects xylene isomers at low ppm levels with multiple sensing features. Combined with pattern-recognition algorithms, a sole ambipolar FET sensor, rather than arrays of sensors, can discriminate highly similar xylene structural isomers from one another. PMID- 26996400 TI - Longitudinal development in the preterm thalamus and posterior white matter: MRI correlations between diffusion weighted imaging and T2 relaxometry. AB - Infants born prematurely are at increased risk of adverse neurodevelopmental outcome. The measurement of white matter tissue composition and structure can help predict functional performance. Specifically, measurements of myelination and indicators of myelination status in the preterm brain could be predictive of later neurological outcome. Quantitative imaging of myelin could thus serve to develop biomarkers for prognosis or therapeutic intervention; however, accurate estimation of myelin content is difficult. This work combines diffusion MRI and multi-component T2 relaxation measurements in a group of 37 infants born very preterm and scanned between 27 and 58 weeks equivalent gestational age. Seven infants have longitudinal data at two time points that we analyze in detail. Our aim is to show that measurement of the myelin water fraction is achievable using widely available pulse sequences and state-of-the-art algorithmic modeling of the MR imaging procedure and that a multi-component fitting routine to multi-shell diffusion weighted data can show differences in neurite density and local spatial arrangement in grey and white matter. Inference on the myelin water fraction allows us to demonstrate that the change in diffusion properties of the preterm thalamus is not solely due to myelination (that increase in myelin content accounts for about a third of the observed changes) whilst the decrease in the posterior white matter T2 has no significant component that is due to myelin water content. This work applies multi-modal advanced quantitative neuroimaging to investigate changing tissue properties in the longitudinal setting. Hum Brain Mapp 37:2479-2492, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26996401 TI - A microscopy study of hyphal growth of Penicillium rubens on gypsum under dynamic humidity conditions. AB - To remediate indoor fungal growth, understanding the moisture relations of common indoor fungi is crucial. Indoor moisture conditions are commonly quantified by the relative humidity (RH). RH is a major determinant of the availability of water in porous indoor surfaces that fungi grow on. The influence of steady-state RH on growth is well understood. Typically, however, the indoor RH constantly changes so that fungi have to endure frequent periods of alternating low and high RH. Knowledge of how common indoor fungi survive and are affected by the low-RH periods is limited. In particular, the specific effects of a drop in RH on the growth of the mycelium remain unclear. In this work, video microscopy was used to monitor hyphal growth of Penicillium rubens on gypsum substrates under controlled dynamic humidity conditions. The effect of a single period of low RH (RH = 50 90%) interrupting favourable conditions (RH = 97%) was tested. It was found that hyphal tips ceased to extend when exposed to any tested decrease in RH. However, new hyphal growth always emerges, seemingly from the old mycelium, suggesting that this indoor fungus does not rely only on conidia to survive the humidity patterns considered. These findings are a fundamental step in unravelling the effect of RH on indoor fungal growth. PMID- 26996402 TI - Program Director Survey: Attitudes Regarding Child Neurology Training and Testing. AB - BACKGROUND: As a result of major clinical and scientific advances and changes in clinical practice, the role of adult neurology training for Child Neurology and Neurodevelopmental Disability (NDD) certification has become controversial. The most recently approved requirements for board eligibility for child neurology and neurodevelopmental disability residents still include 12 months in adult neurology rotations. The objective of this study was to assess United States child neurology and neurodevelopmental disability residency program directors' opinions regarding optimal residency training. METHODS: The authors developed an 18-item questionnaire and contacted all 80 child neurology and neurodevelopmental disability program directors via e-mail, using SurveyMonkey. RESULTS: A total of 44 program directors responded (55%), representing programs that train 78 categorical and 94 total resident positions, approximately 70% of those filled in the match. Respondents identified multiple areas where child neurology residents need more training, including genetics and neuromuscular disease. A substantial majority (73%) believed child neurology and neurodevelopmental disability residents need less than 12 adult neurology training months; however, most (75%) also believed adult hospital service and man-power needs (55%) and finances (34%) would pose barriers to reducing adult neurology. Most (70%) believed reductions in adult neurology training should be program flexible. A majority believed the written initial certification examination should be modified with more child neurology and fewer basic neuroscience questions. Nearly all (91%) felt the views of child neurology and neurodevelopmental disability program directors are under represented within the Accreditation Council for Graduate Medical Education Residency Review Committee. CONCLUSIONS: The requirement for 12 adult neurology months for Child Neurology and Neurodevelopmental Disability certification is not consistent with the views of the majority of program directors, who favor more training in subspecialized fields of child neurology. PMID- 26996403 TI - Aspects of Attention in Rett Syndrome. AB - BACKGROUND: We sought to examine fundamental aspects of attention in children with Rett syndrome, a severely disabling neurodevelopmental disorder caused by spontaneous mutations in the X-linked MECP2 gene. To gauge their attention, we used eye tracking, which bypasses the profound impairments in expressive language and hand use in Rett syndrome. We report two aspects of attention-shifting and sustaining-basic abilities known to drive cognitive growth. METHODS: Two groups were compared: those with Rett syndrome (N = 20; 3-15 years) and a typically developing comparison group (N = 14; 3-16 years), using a task in which an attractive central stimulus was followed, after a short gap, by a dynamic target presented to one side. Time to shift to the target location (reactive and anticipatory saccades) and time fixating the target were assessed. RESULTS: Children with Rett syndrome were consistently slower to shift (largely because of fewer anticipations); their reactive saccades were also slower than those of typically developing children, but not significantly so. The Rett syndrome group spent considerable time looking at the target (over 75% of available time), although significantly less so than the typically developing group. CONCLUSIONS: These findings indicate that children with Rett syndrome could maintain attention on a stimulus and orient relatively quickly to the appearance of a target in the visual field. However, they had difficulty in anticipating predictable events, a difficulty in endogenous attention that is likely to have deleterious implications for executive functioning. PMID- 26996404 TI - Long-Term Neurocognitive, Psychosocial, and Magnetic Resonance Imaging Outcomes in Pediatric-Onset Acute Disseminated Encephalomyelitis. AB - BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder that is usually self-limited. Recent studies have suggested ongoing neurological deficits and neurocognitive impairment in these patients. Little information on the correlation of clinical and neuroimaging markers in ADEM is available. We examined potential clinical factors (e.g., age of onset, acute symptom duration, magnetic resonance imaging [MRI] lesions) and their relation to neurocognitive and psychosocial outcomes. METHODS: This is a retrospective chart review of consecutive pediatric patients diagnosed with ADEM between 2006 and 2012. Patients were evaluated with standard neurological assessment, MRI of the brain, and neuropsychological evaluation. RESULTS: Twenty-three patients with ADEM with average age at neuropsychological assessment of 10.1 years (+/-3.50) were included. Five (22.7%) patients were impaired on three or more neurocognitive measures. Psychosocial problems were reported in 20%-40% of patients. Earlier age of onset was correlated with poorer sustained attention and psychosocial problems, whereas acute symptom duration and Expanded Disability Status Scale were not. MRI outcomes were correlated with psychosocial outcomes but not neuropsychological findings. CONCLUSIONS: Our findings suggest lingering cognitive and psychosocial deficits in children with a history of ADEM. Clinical features and MRI findings correlated more strongly with psychosocial outcomes than cognitive functioning. Further studies are needed to confirm relationships and other possible contributing factors to lingering deficits. PMID- 26996405 TI - Oral Dimethyl Fumarate in Children With Multiple Sclerosis: A Dual-Center Study. AB - BACKGROUND: First-line injectable therapies for multiple sclerosis in children may be ineffective or not well-tolerated. There is therefore an urgent need to explore oral medications for pediatric multiple sclerosis. We review our dual center experience with oral dimethyl fumarate. METHODS: This study was a retrospective review of children 18 years of age or less with multiple sclerosis treated with dimethyl fumarate at Yale University and the University of Colorado. Clinical, demographic, and magnetic resonance imaging parameters were analyzed. RESULTS: We identified 13 children treated with oral dimethyl fumarate for a median of 15.0 months (range, 1 to 25). Dimethyl fumarate was utilized as first line therapy in five children (38%). Ten children (77%) tolerated dose escalation to the usual adult dose of 240 mg twice daily. Nine children had >=12 months of follow-up on treatment. Eight of nine (89%) displayed stabilized or reduced relapse rates and disability scores on treatment. Nine children underwent brain magnetic resonance imaging performed after 12 or more months of therapy. New T2 lesions were observed in three children (33%), one of whom had been nonadherent to treatment. Common side effects included facial flushing (8/13, 62%), gastrointestinal discomfort (7/13, 54%), rash (3/13, 23%), and malaise (2/13, 15%). Three children (23%) discontinued treatment because of side effects. No patients displayed laboratory abnormalities including lymphopenia or abnormal liver transaminases. There were no reported infections. CONCLUSIONS: Oral dimethyl fumarate appears to be safe and generally well tolerated in children with multiple sclerosis. Formal clinical trials to evaluate efficacy are ongoing. PMID- 26996407 TI - Environmental treasures: co-isolation of the first marine Chlamydiae and its protozoan host. PMID- 26996406 TI - Factors Associated with Amputation after Popliteal Vascular Injuries. AB - BACKGROUND: Popliteal artery trauma has the highest rate of limb loss of all peripheral vascular injuries. The objectives of this study were to evaluate outcomes after popliteal vascular injury and to identify predictors of amputation. METHODS: Retrospective data over a 14-year period were collected for patients with popliteal artery with or without vein injuries. Patient demographics, mechanism of injury, Injury Severity Score (ISS), Mangled Extremity Severity Score (MESS), and physiologic parameters were extracted. Time to operative intervention, operative time, type of vascular repair, need for concomitant orthopedic procedures, and outcomes including amputation rate, and in hospital mortality were recorded. RESULTS: Fifty-one patients were found to have popliteal artery injuries, with a median age of 25 (range 10-70 years). The median ISS was 9, and the mean extremity Abbreviated Injury Severity score was 3. The mechanism of injury was blunt for 43% and penetrating for 57%. Fasciotomies were performed in 74% of patients and 64% of patients underwent combined orthopedic and vascular procedures. Overall, 66% of these patients had their vascular procedure performed first. Ten patients required amputation: 1 immediate and 9 after attempted limb salvage (20%). We found that those patients requiring amputation had a higher incidence of blunt trauma (80% vs. 35%, P = 0.014) and higher MESS score (7.1 vs. 4.7, P = 0.02). There was no difference in the incidence of amputation for those who underwent orthopedic fixation before vascular repair (P = 0.68). CONCLUSIONS: Popliteal vascular injuries continue to be associated with a high risk of amputation. Those patients undergoing attempted limb salvage should be revascularized expediently, but selected patients may undergo orthopedic stabilization before vascular repair without increased risk of limb loss. PMID- 26996408 TI - Entanglements of instruments and media in investigating organic life. AB - The question what constitutes organic life might be answered variously. This special issue explores how the rendering of life throughout the history of biology has been shaped by various instruments and media. While acknowledging the significance of the theoretical and social scenes of inquiry in which specific tools and techniques develop, and which delimit epistemic possibilities for making sense of life, the issue draws attention to material practices and instrumental mediations in experimental studies of life. Although it might seem self-evident that biology takes as its object of inquiry living organisms, it is productive to regard its subject matter as organic media rather than discrete organisms. The papers gathered in this issue show the rich potential for the critical study of how organic life has been constituted through the tools used to mediate its study. PMID- 26996409 TI - To be or not to be alive: How recent discoveries challenge the traditional definitions of viruses and life. AB - Three major discoveries have recently profoundly modified our perception of the viral world: molecular ecologists have shown that viral particles are more abundant than cells in natural environments; structural biologists have shown that some viruses from the three domains of life, Bacteria, Eukarya and Archaea, are evolutionarily related, and microbiologists have discovered giant viruses that rival with cells in terms of size and gene content. I discuss here the scientific and philosophical impact of these discoveries on the debates over the definition, nature (living or not), and origin of viruses. I suggest that viruses have often been considered non-living, because they are traditionally assimilated to their virions. However, the term virus describes a biological process and should integrate all aspects of the viral reproduction cycle. It is especially important to focus on the intracellular part of this cycle, the virocell, when viral information is actively expressed and reproduced, allowing the emergence of new viral genes. The virocell concept theoretically removes roadblocks that prevent defining viruses as living organisms. However, defining a "living organism" remains challenging, as indicated by the case of organelles that evolved from intracellular bacteria. To bypass this problem, I suggest considering that all biological entities that actively participate in the process of life are living. PMID- 26996410 TI - Embryos, microscopes, and society. AB - Embryos have different meanings for different people and in different contexts. Seen under the microscope, the biological embryo starts out as one cell and then becomes a bunch of cells. Gradually these divide and differentiate to make up the embryo, which in humans becomes a fetus at eight weeks, and then eventually a baby. At least, that happens in those cases that carry through normally and successfully. Yet a popular public perception imagines the embryo as already a little person in the very earliest stages of development, as if it were predictably to become an adult. In actuality, cells can combine, pull apart, and recombine in a variety of ways and still produce embryos, whereas most embryos never develop into adults at all. Biological embryos and popular imaginations of embryos diverge. This paper looks at some of the historical reasons for and social implications of that divergence. PMID- 26996411 TI - What roles for viruses in origin of life scenarios? AB - Important roles in origin of life (OL) scenarios have been and still are attributed to viruses. Yet the strict dependence of viruses on cells for their multiplication has been widely acknowledged since the first decades of the 20th century. How could viruses play critical roles in the OL if life relies on cellular organization and if viruses are defined as parasites of cells? In other words, how could viruses play a role in the emergence of cellular life if the existence of cells is a prerequisite for the existence of viruses? This paper investigates this issue and describes past and current OL scenarios conferring viruses with important roles, thereby completing the work of historian of science and physician Scott Podolsky who identified three major roles of viruses in past OL scenarios. Some objections raised by present OL scenarios conferring viruses with an important role are discussed. I argue that disagreements concerning the roles of viruses in OL scenarios stem from the different concepts of life and of virus scientists defend. Investigating the roles of viruses in OL scenarios not only helps identifying different ways to define life in the context of OL theorizing. It also offers the opportunity to better understand how viruses could be conceptualized. The relevance of the replication-first versus metabolism-first dichotomy in OL theorizing is briefly discussed. PMID- 26996413 TI - Abnormality of low frequency cerebral hemodynamics oscillations in TBI population. AB - Functional Near Infrared Spectroscopy (fNIRS) can non-invasively capture dynamic cognitive activation and underlying physiological processes by measuring changes in oxy- and deoxy-hemoglobin levels, correlated to brain activation. It is a portable, inexpensive and user-friendly device which is easily adapted to the outpatient setting for the assessment of cognitive functions after Traumatic Brain Injury (TBI). Low frequency oscillations in hemodynamic signal, attributed in the literature to cerebral autoregulation, were assessed using recently introduced metrics, Oxygenation Variability (OV Index), obtained from oxy/deoxy hemoglobin variations in response to mental tasks for a group of healthy control (HC, n=14) and TBI (n=29). Participants responded to an action complexity judgment task (evaluating the complexity of daily life activities by classifying the number of steps as "few" or "many") with a varying degree of cognitive load to produce brain activation. During the task, we measured blood variations with fNIRS and analyzed OV Index changes. Mean OV indices, corresponding to high complexity tasks, are higher than that of low complexity tasks in the HC group, revealing strong parametric effect (0.039+/-0.017 for low, 0.057+/-0.036 for high, p-value=0.069). However, no significant difference has been recorded for the OV indexes for two different loads in the TBI group (0.055+/-0.033 for low, 0.054+/-0.035 for high, p=0.9). OV index metrics proves to be sensitive to chronic TBI and can potentially be used to separate subpopulations TBI vs. HC. Noticeable differences in OV index spatial distributions between subpopulations have been observed. PMID- 26996414 TI - Recombinant FIP-gat, a Fungal Immunomodulatory Protein from Ganoderma atrum, Induces Growth Inhibition and Cell Death in Breast Cancer Cells. AB - FIP-gat, an immunomodulatory protein isolated from Ganoderma atrum, is a new member of the FIP family. Little is known, however, about its expressional properties and antitumor activities. It was availably expressed in Escherichia coli with a total yield of 29.75 mg/L. The migration of recombinant FIP-gat (rFIP gat) on SDS-PAGE corresponded to the predicted molecular mass, and the band was correctly detected by a specific antibody. To characterize the direct effects of rFIP-gat on MDA-MB-231 breast cancer cells, MDA-MB-231 cells were treated with different concentrations of rFIP-gat in vitro; the results showed that this protein could reduce cell viability dose-dependently with a median inhibitory concentration (IC50) of 9.96 MUg/mL and agglutinate the MDA-MB-231 cells at a concentration as low as 5 MUg/mL. Furthermore, FIP-gat at a concentration of 10 MUg/mL can induce significant growth inhibition and cell death in MDA-MB-231 cells. Notably, FIP-gat treatment triggers significant cell cycle arrest at the G1/S transition and pronounced increase in apoptotic cell population. Molecular assays based on microarray and real-time PCR further revealed the potential mechanisms encompassing growth arrest, apoptosis, and autophagy underlying the phenotypic effects. PMID- 26996415 TI - Birthplace as the midwife's work place: How does place of birth impact on midwives? AB - BACKGROUND: In, many high and middle-income countries, childbearing women have a variety of birthplaces available to them including home, birth centres and traditional labour wards. There is good evidence indicating that birthplace impacts on outcomes for women but less is known about the impact on midwives. AIM: To explore the way that birthplace impacts on midwives in Australia and the United Kingdom. METHOD: A qualitative descriptive study was undertaken. Data were gathered through focus groups conducted with midwives in Australia and in the United Kingdom who worked in publicly-funded maternity services and who provided labour and birth care in at least two different settings. FINDINGS: Five themes surfaced relating to midwifery and place including: 1. practising with the same principles; 2. creating ambience: controlling the environment; 3. workplace culture: being watched 4. Workplace culture: "busy work" versus "being with"; and 5. midwives' response to place. DISCUSSION: While midwives demonstrate a capacity to be versatile in relation to the physicality of birthplaces, workplace culture presents a challenge to their capacity to "be with" women. CONCLUSION: Given the excellent outcomes of midwifery led care, we should focus on how we can facilitate the work of midwives in all settings. This study suggests that the culture of the birthplace rather than the physicality is the highest priority. PMID- 26996416 TI - Periodontal medicine: work in progress! PMID- 26996412 TI - Prion-like domains as epigenetic regulators, scaffolds for subcellular organization, and drivers of neurodegenerative disease. AB - Key challenges faced by all cells include how to spatiotemporally organize complex biochemistry and how to respond to environmental fluctuations. The budding yeast Saccharomyces cerevisiae harnesses alternative protein folding mediated by yeast prion domains (PrDs) for rapid evolution of new traits in response to environmental stress. Increasingly, it is appreciated that low complexity domains similar in amino acid composition to yeast PrDs (prion-like domains; PrLDs) found in metazoa have a prominent role in subcellular cytoplasmic organization, especially in relation to RNA homeostasis. In this review, we highlight recent advances in our understanding of the role of prions in enabling rapid adaptation to environmental stress in yeast. We also present the complete list of human proteins with PrLDs and discuss the prevalence of the PrLD in nucleic-acid binding proteins that are often connected to neurodegenerative disease, including: ataxin 1, ataxin 2, FUS, TDP-43, TAF15, EWSR1, hnRNPA1, and hnRNPA2. Recent paradigm-shifting advances establish that PrLDs undergo phase transitions to liquid states, which contribute to the structure and biophysics of diverse membraneless organelles. This structural functionality of PrLDs, however, simultaneously increases their propensity for deleterious protein-misfolding events that drive neurodegenerative disease. We suggest that even these PrLD misfolding events are not irreversible and can be mitigated by natural or engineered protein disaggregases, which could have important therapeutic applications. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease. PMID- 26996417 TI - The efficacy and safety of cold-induced lipolysis in the treatment of pseudogynecomastia. AB - BACKGROUND: The treatment options for pseudogynecomastia have been limited. Cold induced lipolysis provides a noninvasive, localized subcutaneous adipocyte destruction by inducing adipocyte apoptosis. OBJECTIVE: This study has been designed to evaluate the efficacy of cold-induced lipolysis as a treatment modality for pseudogynecomastia. METHODS: In this 28-week prospective trial, a total of 12 male pseudogynecomastia patients (Korean) were treated twice with cold-induced lipolysis. Efficacy was determined by chest circumference, ultrasonographic measurement of fat thickness, Simon's Gynecomastia class (SGC), photographic assessment, and the patient's satisfaction (baseline, weeks 4, 8, 16, and 28). Using a questionnaire, safety was evaluated at each visit. RESULTS: For 10 subjects that completed the trial, chest circumference and fat thickness significantly improved by week 8. This same improvement was gradually noticed through week 28. The patients SGC scores continuously decreased after two sessions. Photographic assessment showed an improvement until week 28. The result of the patient's satisfaction score was also meaningful. While there were no adverse events observed, transient pain and bruising at the treatment site were noticed. LIMITATIONS: We recruited a limited number of participants. Also, we could not exclude there might be other individual factors in association with the patients pseudogynecomastia. CONCLUSION: Cold-induced lipolysis is a safe, effective therapeutic option in the treatment of pseudogynecomastia. Lasers Surg. Med. 48:584-589, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26996418 TI - The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis. AB - Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis. PMID- 26996419 TI - Dual-Energy X-Ray Absorptiometry: Beyond Bone Mineral Density Determination. AB - Significant improvements in dual-energy X-ray absorptiometry (DXA) concerning quality, image resolution and image acquisition time have allowed the development of various functions. DXA can evaluate bone quality by indirect analysis of micro and macro-architecture of the bone, which and improve the prediction of fracture risk. DXA can also detect existing fractures, such as vertebral fractures or atypical femur fractures, without additional radiologic imaging and radiation exposure. Moreover, it can assess the metabolic status by the measurement of body composition parameters like muscle mass and visceral fat. Although more studies are required to validate and clinically use these parameters, it is clear that DXA is not just for bone mineral densitometry. PMID- 26996420 TI - In Vivo Rodent Models of Skeletal Muscle Adaptation to Decreased Use. AB - Skeletal muscle possesses plasticity and adaptability to external and internal physiological changes. Due to these characteristics, skeletal muscle shows dramatic changes depending on its response to stimuli such as physical activity, nutritional changes, disease status, and environmental changes. Modulation of the rate of protein synthesis/degradation plays an important role in atrophic responses. The purpose of this review is to describe different features of skeletal muscle adaptation with various models of deceased use. In this review, four models were addressed: immobilization, spinal cord transection, hindlimb unloading, and aging. Immobilization is a form of decreased use in which skeletal muscle shows electrical activity, tension development, and motion. These results differ by muscle group. Spinal cord transection was selected to simulate spinal cord injury. Similar to the immobilization model, dramatic atrophy occurs in addition to fiber type conversion in this model. Despite the fact that electromyography shows unremarkable changes in muscle after hindlimb unloading, decreased muscle mass and contractile force are observed. Lastly, aging significantly decreases the numbers of muscle fibers and motor units. Skeletal muscle responses to decreased use include decreased strength, decreased fiber numbers, and fiber type transformation. These four models demonstrated different changes in the skeletal muscle. This review elucidates the different skeletal muscle adaptations in these four decreased use animal models and encourages further studies. PMID- 26996421 TI - How to Establish Clinical Prediction Models. AB - A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice. PMID- 26996424 TI - Differentiated Thyroid Cancer in Asians. PMID- 26996422 TI - In Vivo Models for Incretin Research: From the Intestine to the Whole Body. AB - Incretin hormones are produced by enteroendocrine cells (EECs) in the intestine in response to ingested nutrient stimuli. The incretin effect is defined as the difference in the insulin secretory response between the oral glucose tolerance test and an isoglycemic intravenous glucose infusion study. The pathophysiology of the decreased incretin effect has been studied as decreased incretin sensitivity and/or beta-cell dysfunction per se. Interestingly, robust increases in endogenous incretin secretion have been observed in many types of metabolic/bariatric surgery. Therefore, metabolic/bariatric surgery has been extensively studied for incretin physiology, not only the hormones themselves but also alterations in EECs distribution and genetic expression levels of gut hormones. These efforts have given us an enormous understanding of incretin biology from synthesis to in vivo behavior. Further innovative studies are needed to determine the mechanisms and targets of incretin hormones. PMID- 26996425 TI - Comparison of Fixed versus Calculated Activity of Radioiodine for the Treatment of Graves Disease in Adults. AB - BACKGROUND: Radioactive iodine as a treatment modality has been shown in several studies to be a safe and effective therapy for Graves disease. However, there is still no uniformity regarding optimal dosing method. The aim of this study is to compare the efficacy of calculated and fixed dosing of radioiodine for the treatment of Graves disease. METHODS: A hundred twenty-two patients diagnosed with Graves disease were randomized to receive either fixed or calculated dose of radioiodine. Those randomized to fixed activity received either low fixed activity at 9.9 mCi for thyroid gland size <40 g or high fixed activity at 14.9 mCi for thyroid gland size 40 to 80 g, and those grouped to calculated activity received 160 MUCi/g of thyroid tissue adjusted for 24 hours radioiodine uptake. Thyroid function tests (free thyroxine [T4] and thyroid stimulating hormone [TSH]) were monitored at 10, 16, and 24 weeks after radioactive iodine therapy. The primary outcome, treatment failure was defined as persistently elevated free T4 and low TSH. RESULTS: Of the 122 patients randomized, 56 in the fixed dose group and 56 in the calculated dose group completed the follow-up. At the end of 6 months, the percentage of treatment failure was 37.50% in the calculated dose group versus 19.64% in the fixed dose group with a relative risk of 0.53 (95% confidence interval, 0.28 to 0.98) favoring the fixed dose group. CONCLUSION: Fixed dose radioiodine has a significantly lower incidence of persistent hyperthyroidism at 6 months post-radioactive therapy. PMID- 26996423 TI - Mechanisms of Vascular Calcification: The Pivotal Role of Pyruvate Dehydrogenase Kinase 4. AB - Vascular calcification, abnormal mineralization of the vessel wall, is frequently associated with aging, atherosclerosis, diabetes mellitus, and chronic kidney disease. Vascular calcification is a key risk factor for many adverse clinical outcomes, including ischemic cardiac events and subsequent cardiovascular mortality. Vascular calcification was long considered to be a passive degenerative process, but it is now recognized as an active and highly regulated process similar to bone formation. However, despite numerous studies on the pathogenesis of vascular calcification, the mechanisms driving this process remain poorly understood. Pyruvate dehydrogenase kinases (PDKs) play an important role in the regulation of cellular metabolism and mitochondrial function. Recent studies show that PDK4 is an attractive therapeutic target for the treatment of various metabolic diseases. In this review, we summarize our current knowledge regarding the mechanisms of vascular calcification and describe the role of PDK4 in the osteogenic differentiation of vascular smooth muscle cells and development of vascular calcification. Further studies aimed at understanding the molecular mechanisms of vascular calcification will be critical for the development of novel therapeutic strategies. PMID- 26996426 TI - Effects of experimentally sustained elevated testosterone on incubation behaviour and reproductive success in female great tits (Parus major). AB - In many seasonally breeding birds, female and male testosterone (T) levels peak at the start of the breeding season, coinciding with pair bonding and nesting activities. Shortly after the onset of egg laying, T levels slowly decline to baseline levels in both sexes, but more rapidly so in females. During this period, T in males may still function to facilitate territorial behaviour, mate guarding and extra pair copulations, either via short lasting peaks or elevated basal levels of the hormone. In some species, however, males become insensitive to increased T after the onset of egg laying. It has been postulated that in these species bi-parental care is essential for offspring survival, as T is known to inhibit paternal care. However, only very few studies have analysed this for females. As females are heavily involved in parental care, they too might become insensitive to T after egg laying. Alternatively, because territorial defence, mate guarding and extra pair copulations are expected to be less important for females than for males, they may not have had the need to evolve a mechanism to become insensitive to T during the period of maternal care, because their natural T levels are never elevated during this part of the breeding season anyway. We tested these alternative hypotheses in female great tits (Parus major). Male great tits have previously been shown to be insensitive to T after egg laying with regard to nestling feeding behaviour (but not song rate). When females had started nest building, we experimentally elevated their T levels up to the nestling feeding phase, and measured incubation behaviour (only females incubate) and reproductive success. T did not significantly affect nest building or egg laying behaviour, although egg laying tended to be delayed in T females. Females with experimentally enhanced T maintained lower temperature during incubation but did not spend less time incubating. This might explain the reduced hatching success of their eggs, smaller brood size and lower number of fledglings we found in this study. As in this species T-dependent behaviour by females during the phase of parental care is not needed, the results support the hypothesis that in this species the need for selection in favour of T-insensitivity did not occur. PMID- 26996427 TI - A comparison of two methods for the assessment of stress axis activity in wild fish in relation to wastewater effluent exposure. AB - Riverine fish are particularly vulnerable to chemical exposure - rivers receive chemicals of anthropogenic origin from a variety of sources, one of the most significant being the chemically complex effluents discharged by wastewater treatment works (WWTWs). The extent to which non-reproductive components of the endocrine system in fish may be vulnerable to interference by contaminants associated with WWTW effluent is not well understood, but a significant body of evidence does suggest that contaminants present in the aquatic environment may interfere with the normal function of the neuroendocrine stress axis in fish. Field investigations of stress axis function in free-living populations of fish by measurement of hormone concentrations in blood can be confounded by the remoteness of sampling locations and the size of target species. Two methods for assessing stress axis reactivity in situations where blood samples are unavailable were compared in three-spined sticklebacks in relation to their exposure to WWTWs effluent. Sticklebacks were sampled in two successive years at fifteen sites in north-west England impacted by WWTW effluent and the response of each fish to the combined stressor of capture and a brief period of confinement was evaluated using both whole-body immunoreactive cortisol concentrations (WBIC) and the rate of release of cortisol to water (CRTW). A positive relationship between the magnitude of stress-induced CRTW in sticklebacks of both sexes and WWTW effluent concentration at site of capture was observed in both years. However, the relationship between stress-induced WBIC and WWTW effluent concentration was not consistent. These results suggest that components of WWTW effluent can modulate the magnitude of the neuroendocrine stress response in sticklebacks, and by inference in other fish species, but they raise questions about the measurement and interpretation of stress axis responses in fish via endpoints other than blood hormone concentrations. Possible factors underlying the disparity between the CRTW and WBIC results are discussed. PMID- 26996428 TI - Vascular endothelial growth factor and angiopoietins during hen ovarian follicle development. AB - Growth and maturation of ovarian follicles in the hen (Gallus gallus) requires a network of blood vessels that increases in complexity during development. The present studies investigate expression of vascular endothelial growth factor A (VEGF), angiopoietin1 (ANGPT1) and ANGPT2 mRNAs together with their associated receptors (VEGFR and TIE2, respectively) during maturation. Elevated expression of VEGF and its receptors is associated with healthy, compared to atretic, follicles. Levels of VEGF significantly increase, while antagonistic ANGPT2 decrease, in granulosa cells (GC) at follicle selection. By comparison, levels of VEGF, VEGFR1, VEGFR2, ANGPT1, ANGPT2 and TIE2 within the theca layer do not change (P>0.05) relative to developmental stages surrounding follicle selection (6-8mm versus 9-12mm follicles). Prior to selection, treatment with transforming growth factor beta1 (TGFbeta1) significantly increases levels of VEGF in undifferentiated GC from prehierarchal (6-8mm) follicles and actively differentiating GC from selected (9-12 and F4) follicles. Moreover, subsequent to selection follicle stimulating hormone (FSH) increases VEGF expression in GC from 9 to 12mm follicles, and eventually luteinizing hormone (LH) promotes VEGF expression in GC from more mature preovulatory follicles. It is concluded that prior to follicle selection VEGF expression is regulated by autocrine and paracrine actions of TGFbeta1 (but not FSH), and that a comparatively limited extent of vasculature is sufficient to maintain prehierarchal follicles in a viable and undifferentiated state. At follicle selection, FSH- and subsequently LH-induced VEGF production within the GC layer enhance angiogenesis within the theca layer, which facilitates the rapid growth of preovulatory follicles via enhanced incorporation of yellow yolk. PMID- 26996429 TI - Intraocular Inflammation Following Intravitreal Injection of Anti-VEGF Medications for Neovascular Age-Related Macular Degeneration. PMID- 26996430 TI - Affinity-based thermoresponsive precipitation of proteins modified with polymer binding peptides. AB - A 12-mer peptide with an affinity for the meso diad sequence of poly(N isopropylacrylamide) (PNIPAM) was identified through affinity-based peptide screening. A model protein (i.e., human serum albumin (HSA)) chemically modified with the peptide was successfully precipitated with PNIPAM above the lower critical solution temperature (LCST) of PNIPAM. PMID- 26996432 TI - Atherosclerotic renal artery stenosis in the post-CORAL era part 2: new directions in Transcatheter Nephron Salvage following flawed revascularization trials. AB - Unlike endovascular therapeutic studies for atherosclerosis in many other vascular beds, major trials regarding endovascular renovascular revascularization have resulted in a stagnating equipoise. However, every major trial completed for this topic thus far has suffered from major methodological flaws that limit the validity and external generalizability of their results. Furthermore, certain patient populations who are known to benefit from renovascular revascularization may never be studied because they cannot be ethically withheld from life-saving treatment. Forthcoming percutaneous techniques may one day complement angioplasty and stenting in a burgeoning era of cellular modulation and endovascular-directed renal regeneration. PMID- 26996433 TI - Burden of community-onset bloodstream infections, Western Interior, British Columbia, Canada. AB - Although community-onset bloodstream infection (BSI) is recognized as a major cause of morbidity and mortality, its epidemiology has not been well defined in non-selected populations. We conducted population-based surveillance in the Interior Health West region of British Columbia, Canada in order to determine the burden associated with community-onset BSI. A total of 1088 episodes were identified for an overall annual incidence of 117.8/100 000 of which 639 (58.7%) were healthcare-associated (HA) and 449 (41.3%) were community-associated (CA) BSIs for incidences of 69.2 and 48.6/100 000, respectively. The incidence of community-onset BSI varied by age and gender and elderly males were at the highest risk. Overall 964 (88.6%) episodes resulted in hospital admission for a median length of stay of 8 days; the total days of acute hospitalization associated with community-onset BSI was 13 530 days or 1465 days/100 000 population per year. The in-hospital mortality rate was 10.6% (102/964) and this was higher for HA-BSI (72/569, 12.7%) compared to CA-BSI (30/395, 7.6%, P = 0.014) episodes. Community-onset BSI, especially HA-BSI, is associated with a major burden of illness. PMID- 26996431 TI - Phosphorylation of eIF2alpha on Threonine 169 is not required for Trypanosoma brucei cell cycle arrest during differentiation. AB - The trypanosome life cycle consists of a series of developmental forms each adapted to an environment in the relevant insect and/or mammalian host. The differentiation process from the mammalian bloodstream form to the insect-midgut procyclic form in Trypanosoma brucei occurs in two steps in vivo. First proliferating 'slender' bloodstream forms differentiate to non-dividing 'stumpy' forms arrested in G1. Second, in response to environmental cues, stumpy bloodstream forms re-enter the cell cycle and start to proliferate as procyclic forms after a lag during which both cell morphology and gene expression are modified. Nearly all arrested cells have lower rates of protein synthesis when compared to the proliferating equivalent. In eukaryotes, one mechanism used to regulate the overall rate of protein synthesis involves phosphorylation of the alpha subunit of initiation factor eIF2 (eIF2alpha). The effect of eIF2alpha phosphorylation is to prevent the action of eIF2B, the guanine nucleotide exchange factor that activates eIF2 for the next rounds of initiation. To investigate the role of the phosphorylation of eIF2alpha in the life cycle of T. brucei, a cell line was made with a single eIF2alpha gene that contained the phosphorylation site, threonine 169, mutated to alanine. These cells were capable of differentiating from proliferating bloodstream form cells into arrested stumpy forms in mice and into procyclic forms in vitro and in tsetse flies. These results indicate that translation attenuation mediated by the phosphorylation of eIF2alpha on threonine 169 is not necessary for the cell cycle arrest associated with these differentiation processes. PMID- 26996434 TI - Multicomponent access to indolo[3,3a-c]isoquinolin-3,6-diones: formal synthesis of (+/-)-plicamine. AB - The complete tetracyclic core structure of plicamine, a novel Amaryllidaceae-type alkaloid, was expeditously prepared by a Ugi four-component condensation reaction, followed by a one-pot sequential phenolic oxidation and intramolecular coupling process. The employment of this strategy resulted in a rapid, formal synthesis of (+/-)-plicamine. PMID- 26996435 TI - Extracurricular activities of medical school applicants. AB - PURPOSE: The purpose of this study was to investigate medical school applicants' involvements in extracurricular activities including medical volunteering/community services, nonmedical community services, club activities, leadership role, and research. METHODS: Extracurricular characteristics were compared for 448 applicants (223 males and 225 females) who applied to Kangwon Medical School in 2013 to 2014. Frequency analysis, chi-square test, and simple correlation were conducted with the collected data. RESULTS: The 448 applicants participated in medical volunteer/community services (15.3%), nonmedical community services (39.8%), club activities (22.9%), club officials (10%), and research (13.4%). On average, applicants from foreign universities participated in 0.9 medical volunteer/community service, 0.8 nonmedical community service, 1.7 club activities, and 0.6 research work. On the other hand, applicants from domestic universities reported 0.2 medical volunteer/community service, 1.0 nonmedical community service, 0.7 club activity, and 0.3 research. CONCLUSION: Involvement in extracurricular activities was extensive for medical school applicants. Participation in extracurricular activities differed between applicants from foreign and domestic universities. Females consistently reported greater participation in extracurricular activities than males. The data can be helpful for admission committees to recruit well-rounded applicants and compare between applicants with similar academic backgrounds. PMID- 26996436 TI - A pilot study on the evaluation of medical student documentation: assessment of SOAP notes. AB - PURPOSE: The purpose of this study was evaluation of the current status of medical students' documentation of patient medical records. METHODS: We checked the completeness, appropriateness, and accuracy of 95 Subjective-Objective Assessment-Plan (SOAP) notes documented by third-year medical students who participated in clinical skill tests on December 1, 2014. Students were required to complete the SOAP note within 15 minutes of an standard patient (SP)-encounter with a SP complaining rhinorrhea and warring about meningitis. RESULTS: Of the 95 SOAP notes reviewed, 36.8% were not signed. Only 27.4% documented the patient's symptoms under the Objective component, although all students completed the Subjective notes appropriately. A possible diagnosis was assessed by 94.7% students. Plans were described in 94.7% of the SOAP notes. Over half the students planned workups (56.7%) for diagnosis and treatment (52.6%). Accurate documentation of the symptoms, physical findings, diagnoses, and plans were provided in 78.9%, 9.5%, 62.1%, and 38.0% notes, respectively. CONCLUSION: Our results showed that third-year medical students' SOAP notes were not complete, appropriate, or accurate. The most significant problems with completeness were the omission of students' signatures, and inappropriate documentation of the physical examinations conducted. An education and assessment program for complete and accurate medical recording has to be developed. PMID- 26996438 TI - Rechargeable dual-metal-ion batteries for advanced energy storage. AB - Energy storage devices are more important today than any time before in human history due to the increasing demand for clean and sustainable energy. Rechargeable batteries are emerging as the most efficient energy storage technology for a wide range of portable devices, grids and electronic vehicles. Future generations of batteries are required to have high gravimetric and volumetric energy, high power density, low price, long cycle life, high safety and low self-discharge properties. However, it is quite challenging to achieve the above properties simultaneously in state-of-the-art single metal ion batteries (e.g. Li-ion batteries, Na-ion batteries and Mg-ion batteries). In this contribution, hybrid-ion batteries in which various metal ions simultaneously engage to store energy are shown to provide a new perspective towards advanced energy storage: by connecting the respective advantages of different metal ion batteries they have recently attracted widespread attention due to their novel performances. The properties of hybrid-ion batteries are not simply the superposition of the performances of single ion batteries. To enable a distinct description, we only focus on dual-metal-ion batteries in this article, for which the design and the benefits are briefly discussed. We enumerate some new results about dual-metal-ion batteries and demonstrate the mechanism for improving performance based on knowledge from the literature and experiments. Although the search for hybrid-ion batteries is still at an early age, we believe that this strategy would be an excellent choice for breaking the inherent disadvantages of single ion batteries in the near future. PMID- 26996439 TI - Overview of Flaxseed Patent Applications for the Reduction of Cholesterol Levels. AB - BACKGROUND: Flaxseed is becoming an increasingly widely used food ingredient. The rising interest of the food industry in this nutraceutical is primarily because of functional nutrients, such as alpha-linolenic acid and lignans, which have health benefits due to their lipid-lowering properties. OBJECTIVE: The objective of this study was to provide an overview of the patenting of flaxseed products with cholesterol-lowering effects. METHOD: Patent applications filed by country of origin were retrieved from the Derwent Innovations Index(r)database. RESULTS: A total of 307 patent documents were identified, of which 184 claim the use of flaxseed or parts of the flax plant in the product formulation, for their lipid lowering effect when consumed by humans. A few of the patent applications contain claims for new products based on flaxseed in isolation, including the preparation of foods designed to inhibit the production of cholesterol. Most of the claims were for flaxseed in the form of oil and in association with other lipid-lowering compounds, mainly for the food industry, in the form of dietary supplements or baked products designed to raise their high-density lipoprotein content, and for treating heart problems. China and the United States are the leading countries of flax-related applications. CONCLUSION: These results may have important implications for the production of functional food products that meet specific societal demands. PMID- 26996440 TI - Morphodynamics of submarine channel inception revealed by new experimental approach. AB - Submarine channels are ubiquitous on the seafloor and their inception and evolution is a result of dynamic interaction between turbidity currents and the evolving seafloor. However, the morphodynamic links between channel inception and flow dynamics have not yet been monitored in experiments and only in one instance on the modern seafloor. Previous experimental flows did not show channel inception, because flow conditions were not appropriately scaled to sustain suspended sediment transport. Here we introduce and apply new scaling constraints for similarity between natural and experimental turbidity currents. The scaled currents initiate a leveed channel from an initially featureless slope. Channelization commences with deposition of levees in some slope segments and erosion of a conduit in other segments. Channel relief and flow confinement increase progressively during subsequent flows. This morphodynamic evolution determines the architecture of submarine channel deposits in the stratigraphic record and efficiency of sediment bypass to the basin floor. PMID- 26996437 TI - Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis. AB - Excessive activation of blood coagulation and neutrophil accumulation have been described in several human cancers. However, whether hypercoagulation and neutrophilia are linked and involved in cancer development is currently unknown. Here we show that spontaneous intestinal tumorigenesis correlates with the accumulation of low-density neutrophils with a pro-tumorigenic N2 phenotype and unprompted neutrophil extracellular traps (NET) formation. We find that increased circulating lipopolysaccharide induces upregulation of complement C3a receptor on neutrophils and activation of the complement cascade. This leads to NETosis, induction of coagulation and N2 polarization, which prompts tumorigenesis, showing a novel link between coagulation, neutrophilia and complement activation. Finally, in a cohort of patients with small but not large intestinal cancer, we find a correlation between neutrophilia and hypercoagulation. This study provides a mechanistic explanation for the tumour-promoting effects of hypercoagulation, which could be used as a new biomarker or as a therapeutic target. PMID- 26996441 TI - Influences of population density on polyandry and patterns of sperm usage in the marine gastropod Rapana venosa. AB - Polyandry is a common mating strategy in animals, with potential for sexual selection to continue post-copulation through sperm competition and/or cryptic female choice. Few studies have investigated the influences of population density on polyandry and sperm usage, and paternity distribution in successive broods of marine invertebrates. The marine gastropod Rapana venosa is ideal for investigating how population density influences the frequency of polyandry and elucidating patterns of sperm usage. Two different population density (12 ind/m(3) and 36 ind/m(3)) treatments with two replications were set to observe reproductive behaviors. Five microsatellite markers were used to identify the frequency of multiple paternity and determine paternal contributions to progeny arrays in 120 egg masses. All of the mean mating frequency, mean number of sires and mean egg-laying frequency were higher at high population density treatment relative to low population density treatment, indicating population density is an important factor affecting polyandry. The last sperm donors achieved high proportions of paternity in 74.77% of egg masses, which supported the "last male sperm precedence" hypothesis. In addition, high variance in reproductive success among R. venosa males were detected, which might have an important influence on effective population size. PMID- 26996444 TI - Na2M2(SO4)3 (M = Fe, Mn, Co and Ni): towards high-voltage sodium battery applications. AB - Sodium-ion-based batteries have evolved as excellent alternatives to their lithium-ion-based counterparts due to the abundance, uniform geographical distribution and low price of Na resources. In the pursuit of sodium chemistry, recently the alluaudite framework Na2M2(SO4)3 has been unveiled as a high-voltage sodium insertion system. In this context, the framework of density functional theory has been applied to systematically investigate the crystal structure evolution, density of states and charge transfer with sodium ions insertion, and the corresponding average redox potential, for Na2M2(SO4)3 (M = Fe, Mn, Co and Ni). It is shown that full removal of sodium atoms from the Fe-based device is not a favorable process due to the 8% volume shrinkage. The imaginary frequencies obtained in the phonon dispersion also reflect this instability and the possible phase transition. This high volume change has not been observed in the cases of the Co- and Ni-based compounds. This is because the redox reaction assumes a different mechanism for each of the compounds investigated. For the polyanion with Fe, the removal of sodium ions induces a charge reorganization at the Fe centers. For the Mn case, the redox process induces a charge reorganization of the Mn centers with a small participation of the oxygen atoms. The Co and Ni compounds present a distinct trend with the redox reaction occurring with a strong participation of the oxygen sublattice, resulting in a very small volume change upon desodiation. Moreover, the average deintercalation potential for each of the compounds has been computed. The implications of our findings have been discussed both from the scientific perspective and in terms of technological aspects. PMID- 26996443 TI - Reversible and Dynamic Fluorescence Imaging of Cellular Redox Self-Regulation Using Fast-Responsive Near-Infrared Ge-Pyronines. AB - Cellular self-regulation of reactive oxygen species (ROS) stress via glutathione (GSH) antioxidant repair plays a crucial role in maintaining redox balance, which affects various physiological and pathological pathways. In this work, we developed a simple yet effective strategy for reversible, dynamic, and real-time fluorescence imaging of ROS stress and GSH repair, based on novel Ge-pyronine dyes (GePs). Unlike the current O-pyronine (OP) dye, the fluorescence of GePs can be quenched in GSH reduction and then greatly restored by ROS (e.g., ClO(-), ONOO(-), and HO(*)) oxidation because of their unique affinity toward thiols. The "on-off" and "off-on" fluorescence switch can complete in 10 and 20 s, respectively, and exhibit excellent reversibility in vitro and in cells. GePs also show excitation in the long wavelength from the deep-red to near-infrared (NIR) (621-662 nm) region, high fluorescence quantum yield (Phi(fl) = 0.32-0.44) in aqueous media, and excellent cell permeability. Our results demonstrated that GePs can be used for real-time monitoring of the reversible and dynamic interconversion between ROS oxidation and GSH reduction in living cells. GePs might be a useful tool for investigating various redox-related physiological and pathological pathways. PMID- 26996442 TI - Bisoprolol pharmacokinetics and body composition in patients with chronic heart failure: a longitudinal study. AB - PURPOSE: We investigated bisoprolol pharmacokinetics, including longitudinal changes and importance of patient characteristics in chronic heart failure. METHODS: Forty-six patients with chronic heart failure (57 % male, NYHA class I/II/III = 2/36/8) were followed for an average of 8 +/- 2 months. At baseline and follow-up, plasma bisoprolol concentrations were determined and body composition was measured using dual-energy X-ray absorptiometry. A bisoprolol pharmacokinetic model was built with non-linear mixed-effects modeling to analyze the association with various parameters of body composition. RESULTS: Mean bisoprolol clearance (10.2 L/h) was 30 % lower than in healthy individuals and correlated with MDRD4-estimated renal function. The mean volume of distribution (230 L) was similar to healthy population and was associated with total body mass and skeletal muscle index (SMI). During follow-up, we observed minor changes in the absorption rate constant (2.83 vs. 2.27 h(-1), P = 0.030) and volume of distribution (227 vs. 250 L, P = 0.004), which are not clinically relevant. CONCLUSIONS: In patients with chronic heart failure, bisoprolol clearance was associated with estimated renal function; thus, in moderately and severely decreased renal function, patients may need to have their dose adjusted. Patients with low body weight or low SMI have greater fluctuations and higher maximal plasma concentrations of bisoprolol because of the lower volume of distribution. Longitudinal changes of bisoprolol pharmacokinetics were not associated with changes in body composition. PMID- 26996445 TI - Geometry, Electronic Structure, and Pseudo Jahn-Teller Effect in Tetrasilacyclobutadiene Analogues. AB - We revealed the origin of the structural features of a series of tetrasilacyclobutadiene analogues based on a detailed study of their electronic structure and the pseudo Jahn-Teller effect (PJTE). Starting with the D4h symmetry of the Si4R4 system with a square four-membered silicon ring as a reference geometry, and employing ab initio calculations of energy profiles along lower-symmetry nuclear displacements in the ground and several excited states, we show that the ground-state boat-like and chair-like equilibrium configurations are produced by the PJT interaction with appropriate excited sates. For Si4F4 a full two-mode b1g-b2g adiabatic potential energy surface is calculated showing explicitly the way of transformation from the unstable D4h geometry to the two equilibrium C2h configurations via the D2h saddle point. The PJTE origin of these structural features is confirmed also by estimates of the vibronic coupling parameters. For Si4R4 with large substituents the origin of their structure is revealed by analyzing the PJT interaction between the frontier molecular orbitals. The preferred chair-like structures of Si4R4 analogues with amido substituents, and heavier germanium-containing systems Ge4R4 (potential precursors for semiconducting materials) are predicted. PMID- 26996447 TI - Heavily doped Au25-xAgx(SC6H11)18(-) nanoclusters: silver goes from the core to the surface. AB - We report a method for heavy doping of the Au25(SR)18 nanocluster (where R = C6H11) with silver through the Ag(I)-thiolate complex induced size/structure transformation of Au23(SR)16(-) into Au25-xAgx(SR)18(-). X-ray crystallographic analysis revealed that Ag dopants are distributed not only in the icosahedral core but also in the surface staple motifs; the latter was not achieved in earlier studies of alloy Au25-xAgx nanoclusters. PMID- 26996446 TI - ROS-generating TiO2 nanoparticles for non-invasive sonodynamic therapy of cancer. AB - The non-invasive photodynamic therapy has been limited to treat superficial tumours, primarily ascribed to poor tissue penetration of light as the energy source. Herein, we designed a long-circulating hydrophilized titanium dioxide nanoparticle (HTiO2 NP) that can be activated by ultrasound to generate reactive oxygen species (ROS). When administered systemically to mice, HTiO2 NPs effectively suppressed the growth of superficial tumours after ultrasound treatments. In tumour tissue, the levels of proinflammatory cytokines were elevated several fold and intense vascular damage was observed. Notably, ultrasound treatments with HTiO2 NPs also suppressed the growth of deeply located liver tumours at least 15-fold, compared to animals without ultrasound treatments. This study provides the first demonstration of the feasibility of using HTiO2 NPs as sensitizers for sonodynamic therapy in vivo. PMID- 26996448 TI - Antifibrotic Actions of Serelaxin - New Roles for an Old Player. AB - Fibrosis represents a failed wound healing response to tissue injury. It is characterized by the accumulation of excess connective tissue and is a significant cause of organ failure, morbidity, and mortality. Fibrotic disorders accompany a wide spectrum of conditions including both systemic and organ specific diseases, for which there is currently no effective cure. Serelaxin, the recombinant form of the major stored and circulating form of human relaxin, has emerged as a pleiotropic drug with rapidly occurring antifibrotic actions. This review discusses the effectiveness of serelaxin as an antifibrotic, and how it augments the actions of several other therapeutics leading to its potential use not only as a monotherapy but also as an adjunct therapy with other antifibrotic agents. PMID- 26996449 TI - Can We 'Read' the Eye-Movement Patterns of Readers? Unraveling the Relationship Between Reading Profiles and Processing Strategies. AB - In an eye-tracking experiment we examined the risky reading hypothesis, in which long saccades and many regressions are considered to be indicative of a proactive reading style (Rayner et al. in Psychol Aging 21(3):448, 2006; Psychol Aging 24(3):755, 2009). We did so by presenting short texts-that confirmed or disconfirmed verb-based implicit causality expectations-to two types of readers: proactive readers (long saccades, many regressions) and conservative readers (short saccades, few regressions). Whereas proactive readers used implicit causality information to predict upcoming referents, and slowed down immediately when they encountered a pronoun that was inconsistent with these verb-based expectations, the conservative readers slowed down much later in the sentence. These findings were consistent with the predictions of the risky reading hypothesis and as such presented novel evidence for the general idea that the eye movement profile of readers reveals valuable information about their processing strategy. PMID- 26996450 TI - Preoperative physiotherapy and short-term functional outcomes of primary total knee arthroplasty. AB - INTRODUCTION: Physiotherapy is an important part of rehabilitation following arthroplasty, but the impact of preoperative physiotherapy on functional outcomes is still being studied. This randomised controlled trial evaluated the effect of preoperative physiotherapy on the short-term functional outcomes of primary total knee arthroplasty (TKA). METHODS: 50 patients with primary knee osteoarthritis who underwent unilateral primary TKA were randomised into two groups: the physiotherapy group (n = 24), whose patients performed physical exercises for six weeks immediately prior to surgery, and the nonphysiotherapy group (n = 26). All patients went through a similar physiotherapy regime in the postoperative rehabilitation period. Functional outcome assessment using the algofunctional Knee Injury and Osteoarthritis Outcome Score (KOOS) scale and range of motion (ROM) evaluation was performed preoperatively, and postoperatively at six weeks and three months. RESULTS: Both groups showed a significant difference in all algofunctional KOOS subscales (p < 0.001). The mean score difference at six weeks and three months was not significant in the sports and recreational activities subscale for both groups (p > 0.05). Significant differences were observed in the time-versus-treatment analysis between groups for the symptoms (p = 0.003) and activities of daily living (p = 0.025) subscales. No significant difference in ROM was found when comparing preoperative measurements and those at three months following surgery, as well as in time-versus-treatment analysis (p = 0.928). CONCLUSION: Six-week preoperative physiotherapy showed no significant impact on short-term functional outcomes (KOOS subscales) and ROM of the knee following primary TKA. PMID- 26996451 TI - Low-threshold optical bistability of graphene-wrapped dielectric composite. AB - We theoretically study the effective third-order nonlinear response and optical bistability of the 3D graphene based composite consisting of graphene wrapped dielectric nanoparticles embedded in dielectric host at terahertz frequencies. Taking into account the nonlinear conductivity of graphene, we derive the analytical expressions for the effective third-order nonlinear coefficient chie3 in weakly nonlinear limit. Moreover, for strong applied fields, the criterion for achieving optical bistability in such a graphene coated sphere, as well as the switching thresholds of optical bistability are discussed. We find that both chie3 and optical bistability are strongly dependent on the Fermi energy of graphene and it is possible to achieve very low switching thresholds under the normal graphene dissipation. We further propose a scheme to study the transmittance of this nonlinear composite slab. These results reveal novel regime of the optical bistability of the transmittance of light. We show that this kind of graphene-wrapped composite, which has tunable and low threshold optical bistability, can be the best candidate for unique nonlinear optical materials. PMID- 26996452 TI - Rare high-impact disease variants: properties and identifications. AB - Although many genome-wide association studies have been performed, the identification of disease polymorphisms remains important. It is now suspected that many rare disease variants induce the association signal of common variants in linkage disequilibrium (LD). Based on recent development of genetic models, the current study provides explanations of the existence of rare variants with high impacts and common variants with low impacts. Disease variants are neither necessary nor sufficient due to gene-gene or gene-environment interactions. A new method was developed based on theoretical aspects to identify both rare and common disease variants by their genotypes. Common disease variants were identified with relatively small odds ratios and relatively small sample sizes, except for specific situations in which the disease variants were in strong LD with a variant with a higher frequency. Rare disease variants with small impacts were difficult to identify without increasing sample sizes; however, the method was reasonably accurate for rare disease variants with high impacts. For rare variants, dominant variants generally showed better Type II error rates than recessive variants; however, the trend was reversed for common variants. Type II error rates increased in gene regions containing more than two disease variants because the more common variant, rather than both disease variants, was usually identified. The proposed method would be useful for identifying common disease variants with small impacts and rare disease variants with large impacts when disease variants have the same effects on disease presentation. PMID- 26996453 TI - [Can preoperative prostate MRI before radical prostatectomy predict extracapsular extension and the side of the index lesion?]. AB - AIM: To evaluate the role of preoperative multi-parametric magnetic resonance imaging (MP-MRI) in patients undergoing radical prostatectomy. Specifically, the accuracy of MP-MRI in detecting extracapsular extension (ECE) and individuating the side of the index lesion have been explored. METHODS: Thirty-five consecutive patients undergoing radical prostatectomy have been retrospectively analyzed. The MRI exam incorporated T2-weighted imaging, diffusion-weighted imaging and dynamic contrast enhancement in all patients. chi(2) test was performed to assess an association between an MP-MRI suggestive of ECE and pathologic ECE; similar tests were performed to study the association between the MRI-detected side of the index lesion and its true localization on final pathology. Univariate logistic regression models were constructed to evaluate possible predictors of ECE, including MP-MRI suspected ECE. RESULTS: Seventeen percent (6/35) of men presented ECE on final pathology. MP-MRI was predictive of pathologic ECE with a negative predictive value and specificity of 93% and 90%, respectively. Global accuracy of MP-MRI in predicting ECE was 86%. MRI-detected ECE was significantly predictive of pathologic ECE on logistic regression (OR: 17.3, 95% CI: 2.2-138.2, P=0.007). Moreover, MRI significantly predicted the side of the index lesion (P=0.012). CONCLUSIONS: In this single center cohort, preoperative MP-MRI was significantly predictive of ECE and side of the index lesion. Further studies are necessary to individuate patients who can benefit from preoperative MP-MRI. LEVEL OF EVIDENCE: 5. PMID- 26996454 TI - Management of anti-Colton(a) alloimmunisation in pregnancy: a case report. PMID- 26996455 TI - The Interaction of Ethanol Ingestion and Social Interaction with an Intoxicated Peer on the Odor-Mediated Response to the Drug in Adolescent Rats. AB - BACKGROUND: Using a social transmission of food preference paradigm in rats, we previously demonstrated that ethanol (EtOH) exposure during adolescence, as either an observer (interaction with an intoxicated conspecific) or demonstrator (intragastric infusion with EtOH), altered the reflexive odor-mediated responses to the drug. The 2 modes of exposure were equivalent in the magnitude of their effects. Human adolescents, however, are likely to experience the drug in a social setting as both an EtOH observer and demonstrator. That is, both interacting with an intoxicated peer and experiencing EtOH's postingestive consequences in conjunction with hematogenic olfaction. Therefore, we tested whether combined adolescent exposure as both an observer and demonstrator differed from either form of individual experience. METHODS: Beginning on postnatal day (P) 29, naive rats received EtOH or water exposures in a social interaction paradigm as either an observer, a demonstrator, or combined experience (where each animal in the interaction was, itself, an observer and demonstrator). Exposures occurred 4 times, once every 48 hours. On P37, the reflexive behavioral response to EtOH odor was tested, using whole-body plethysmography. RESULTS: The odor-mediated responses of adolescent EtOH observers, demonstrators, and combined exposure animals all significantly differed from controls. Compared to controls, however, the magnitude of the behavioral effect was greatest in the combined exposure animals. Moreover, combined exposure as both an EtOH observer and demonstrator significantly differed from either form of individual EtOH experience. CONCLUSIONS: EtOH's component chemosensory qualities are known to be central contributors to its acceptance and increases in the acceptability of EtOH's odor, resulting from a social transmission experience, are predictive of enhanced EtOH avidity in adolescence. Our findings demonstrate that combined exposure as an observer and demonstrator, within a socially relevant framework, may represent a higher risk scenario for increased EtOH avidity in adolescence (and by extension adult persistence) as compared to the individual effects of direct ingestion or social experience with the drug. PMID- 26996456 TI - CpG methylation patterns of human mitochondrial DNA. AB - The epigenetic modification of mitochondrial DNA (mtDNA) is still in controversy. To clarify this point, we applied the gold standard method for DNA methylation, bisulfite pyrosequencing, to examine human mtDNA methylation status. Before bisulfite conversion, BamHI was used to digest DNA to open the loop of mtDNA. The results demonstrated that the linear mtDNA had significantly higher bisulfite conversion efficiency compared with circular mtDNA. Furthermore, the methylation values obtained from linear mtDNA were significantly lower than that of circular mtDNA, which was verified by SEQUENOM MassARRAY. The above impacts of circular structure were also observed in lung DNA samples but not in saliva DNA samples. Mitochondrial genome methylation of blood samples and saliva samples from 14 unrelated individuals was detected. The detected regions covered 83 CpG sites across mtDNA including D-loop, 12 S rRNA, 16 S rRNA, ND1, COXI, ND3, ND4, ND5, CYTB. We found that the average methylation levels of nine regions were all less than 2% for both sample types. In conclusion, our findings firstly show that the circular structure of mtDNA affects bisulfite conversion efficiency, which leads to overestimation of mtDNA methylation values. CpG methylation in human mtDNA is a very rare event at most DNA regions. PMID- 26996457 TI - Absence of hepatitis delta infection in a large rural HIV cohort in Tanzania. AB - OBJECTIVES: The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in Sub-Saharan Africa are ill-defined. The prevalence of HDV infection was determined in HIV/hepatitis B virus (HBV) co-infected individuals in rural Tanzania. METHODS: All HBV-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) were screened for anti-HDV antibodies. For positive samples, a second serological test and nucleic acid amplification were performed. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and -positive patients. RESULTS: Among 222 HIV/HBV co infected patients on ART, 219 (98.6%) had a stored serum sample available and were included in the study. Median age was 37 years, 55% were female, 46% had World Health Organization stage III/IV HIV disease, and the median CD4 count was 179 cells/MUl. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. CONCLUSIONS: No confirmed case of HDV infection was found among over 200 HIV/HBV co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test. PMID- 26996459 TI - Hepatitis C virus in Arabian Gulf countries: Implications and priorities. PMID- 26996460 TI - Epidemiology of hepatitis C virus in the Arabian Gulf countries: Systematic review and meta-analysis of prevalence. AB - OBJECTIVE: The aims of this study were to perform a systematic review and synthesize epidemiological data on hepatitis C virus (HCV) in the Arabian Gulf countries, and to assess the country-specific prevalence among nationals and expatriate populations. METHODS: A systematic review of HCV antibody prevalence and incidence in the Arabian Gulf countries was conducted, based on the items outlined in the PRISMA statement. Meta-analyses were performed incorporating inverse variance weighting and using a random-effects model to pool summary estimates of HCV prevalence among general population groups, for nationals and the entire resident population. RESULTS: A total of 557 prevalence measures and one incidence measure were identified for the Arabian Gulf countries. HCV prevalence among nationals was 0.24% (95% confidence interval (CI) 0.02-0.63) in the United Arab Emirates (UAE), 0.44% (95% CI 0.29-0.62) in Kuwait, 0.51% (95% CI 0.43-0.59) in Qatar, and 1.65% (95% CI 1.40-1.91) in Saudi Arabia. No data were available for Bahrain or Oman. Among the entire resident populations, HCV prevalence was 0.30% (95% CI 0.23-0.38) in Bahrain, 0.41% (95% CI 0.35-0.46) in Oman, 1.06% (95% CI 0.51-1.81) in Qatar, 1.45% (95% CI 0.75-2.34) in Kuwait, 1.63% (95% CI 1.42-1.84) in Saudi Arabia, and 1.64% (95% CI 0.96-2.49) in UAE. A higher prevalence was observed among expatriate populations such as Egyptians. Among the high-risk populations, HCV prevalence was as high as 78.6% in the multi transfused and 74.6% in people who inject drugs. CONCLUSIONS: National-level HCV prevalence in the Arabian Gulf region is comparable to global levels. A higher prevalence is found in specific expatriate populations, reflecting the prevalence in their countries of origin. Most exposures appear to occur in high-risk groups and these are often linked to medical care. PMID- 26996458 TI - Surveillance of antimicrobial resistance in Lebanese hospitals: retrospective nationwide compiled data. AB - Antimicrobial resistance is closely linked to antimicrobial use and is a growing concern worldwide. Antimicrobial resistance increases healthcare costs substantially in many countries, including Lebanon. National data from Lebanon have, in the most part, been limited to a few academic hospitals. The Lebanese Society of Infectious Diseases conducted a retrospective study to better describe the antimicrobial susceptibility patterns of bacterial isolates in Lebanon. Data were based on records retrieved from the bacteriology laboratories of 16 different Lebanese hospitals between January 2011 and December 2013. The susceptibility results of a total 20684 Gram-positive and 55594 Gram-negative bacteria were analyzed. The prevalence rate of methicillin-resistant Staphylococcus aureus was 27.6% and of vancomycin-resistant Enterococcus spp was 1%. Streptococcus pneumoniae had susceptibilities of 46% to oxacillin, 63% to erythromycin, and 98% to levofloxacin. Streptococcus pyogenes had susceptibilities of 94% to erythromycin and 95% to clindamycin. The mean ampicillin susceptibility of Haemophilus influenzae, Salmonella spp, and Shigella spp isolates was 79%, 81.3%, and 62.2%, respectively. The extended-spectrum beta lactamase production rate for Escherichia coli was 32.3% and for Klebsiella spp was 29.2%. Acinetobacter spp showed high resistance to most antimicrobials, with low resistance to colistin (17.1%). Pseudomonas spp susceptibilities to piperacillin-tazobactam and imipenem were lower than 80% (79.7% and 72.8%, respectively). This study provides population-specific data that are valuable in guiding antimicrobial use in Lebanon and neighbouring countries and will help in the establishment of a surveillance system for antimicrobial resistance following the implementation of a nationwide standardization of laboratory methods and data entry. PMID- 26996461 TI - Association of ecological factors with Rift Valley fever occurrence and mapping of risk zones in Kenya. AB - OBJECTIVE: Rift Valley fever (RVF) is a mosquito-borne infection with great impact on animal and human health. The objectives of this study were to identify ecological factors that explain the risk of RVF outbreaks in eastern and central Kenya and to produce a spatially explicit risk map. METHODS: The sensitivity of seven selected ecological variables to RVF occurrence was assessed by generalized linear modelling (GLM). Vegetation seasonality variables (from normalized difference vegetation index (NDVI) data) and 'evapotranspiration' (ET) (metrics) were obtained from 0.25-1km MODIS satellite data observations; 'livestock density' (N/km(2)), 'elevation' (m), and 'soil ratio' (fraction of all significant soil types within a certain county as a function of the total area of that county) were used as covariates. RESULTS: 'Livestock density', 'small vegetation integral', and the second principal component of ET were the most significant determinants of RVF occurrence in Kenya (all p <= 0.01), with high RVF risk areas identified in the counties of Tana River, Garissa, Isiolo, and Lamu. CONCLUSIONS: Wet soil fluxes measured with ET and vegetation seasonality variables could be used to map RVF risk zones on a sub-regional scale. Future outbreaks could be better managed if relevant RVF variables are integrated into early warning systems. PMID- 26996462 TI - Proteomics for exploiting diversity of lupin seed storage proteins and their use as nutraceuticals for health and welfare. AB - Lupins have a variety of both traditional and modern uses. In the last decade, reports assessing the benefits of lupin seed proteins have proliferated and, nowadays, the pharmaceutical industry is interested in lupin proteins for human health. Modern genomics and proteomics have hugely contributed to describing the diversity of lupin storage genes and, above all, proteins. Most of these studies have been centered on few edible lupin species. However, Lupinus genus comprises hundreds of species spread throughout the Old and New Worlds, and these resources have been scarcely explored and exploited. We present here a detailed review of the literature on the potential of lupin seed proteins as nutraceuticals, and the use of -omic tools to analyze seed storage polypeptides in main edible lupins and their diversity at the Lupinus inter- and intra-species level. In this sense, proteomics, more than any other, has been a key approach. Proteomics has shown that lupin seed protein diversity, where post-translational modifications yield a large number of peptide variants with a potential concern in bioactivity, goes far beyond gene diversity. The future extended use of second and third generation proteomics should definitely help to go deeper into coverage and characterization of lupin seed proteome. BIOLOGICAL SIGNIFICANCE: Some important topics concerning storage proteins from lupin seeds are presented and analyzed in an integrated way in this review. Proteomic approaches have been essential in characterizing lupin seed protein diversity, which goes far beyond gene diversity since the protein level adds to the latter differential proteolytic cleavage of conglutin pro proteins and a diverse array of glycosylation forms and sites. Proteomics has also proved helpful for screening and studying Lupinus germplasm with the future aim of exploiting and improving food production, quality, and nutritional values. PMID- 26996463 TI - Comparison of proteomic and metabolomic profiles of two contrasting ecotypes of sweetpotato (Ipomoea batata L.). AB - Sweetpotato has long been acknowledged as a significant contributor of global caloric needs, which continues to be of remarkable economic value. It is an important staple and emergency food in many countries and its annual world production hovers to about 130 million tons. The tubers act as sink and compete for the available photoassimilates eventually leading to the acquisition of nutrients and phytochemicals. Differential display of genes or gene-products, and metabolites causes differences in nutritive value of closely related ecotypes. To better understand the molecular basis for differential nutrient availability and phytochemicals, and exploit the natural genetic variation(s), we aimed at developing proteometabolic profiles of two contrasting ecotypes of sweetpotato. Proteomic analyses led to the identification of 1541 and 1201 proteins in orange fleshed and white fleshed sweetpotato ecotypes, respectively, presumably associated with binding, followed by catalytic, transferase, hydrolase, kinase and transporter activities. Furthermore, metabolome profiling revealed 148 and 126 metabolites in cv. OFSP and WFSP, respectively. This study would provide a basis for future comparative proteometabolomic efforts for sweetpotato, in particular and tuber crops in general. The results would expand our understanding of the proteome as well as metabolome and give new insights into how ecotype specific traits are developed. BIOLOGICAL SIGNIFICANCE: Sweetpotato, the potato of the tropics, is the seventh most important crop worldwide in terms of production for food and additional industrial resources. Over 95% of the global sweet potato is produced in developing countries where it is considered as emergency food. It is also a vegetable, a snack food and confectionery item in most countries. It greatly contributes as a phytochemical source of nutrition and can produce more edible energy per hectare per day than wheat or rice. The adaptability to a wide range of agroecological conditions with least growth requirements makes it a preferred tuber crop of high commercial significance. Despite its nutritional merits, it has always remained outside the realm of large scale functional genomics. Therefore, this study was aimed at constructing the proteomics and metabolomics shared resource for sweetpotato. These data are particularly significant, at least partially due to the fact that the currently available information about sweet potato is under-represented. PMID- 26996464 TI - Bovine lactoferrin regulates cell survival, apoptosis and inflammation in intestinal epithelial cells and preterm pig intestine. AB - Bovine lactoferrin (bLF) may modulate neonatal intestinal inflammation. Previous studies in intestinal epithelial cells (IECs) indicated that moderate bLF doses enhance proliferation whereas high doses trigger inflammation. To further elucidate cellular mechanisms, we profiled the porcine IEC proteome after stimulation with bLF at 0, 0.1, 1 and 10g/L by LC-MS-based proteomics. Key pathways were analyzed in the intestine of formula-fed preterm pigs with and without supplementation of 10g/L bLF. Levels of 123 IEC proteins were altered by bLF. Low bLF doses (0.1-1g/L) up-regulated 11 proteins associated with glycolysis, energy metabolism and protein synthesis, indicating support of cell survival. In contrast, a high bLF dose (10g/L) up-regulated three apoptosis inducing proteins, down-regulated five anti-apoptotic and proliferation-inducing proteins and 15 proteins related to energy and amino acid metabolism, and altered three proteins enhancing the hypoxia inducible factor-1 (HIF-1) pathway. In the preterm pig intestine, bLF at 10g/L decreased villus height/crypt depth ratio and up-regulated the Bax/Bcl-2 ratio and HIF-1alpha, indicating elevated intestinal apoptosis and inflammation. In conclusion, bLF dose-dependently affects IECs via metabolic, apoptotic and inflammatory pathways. It is important to select an appropriate dose when feeding neonates with bLF to avoid detrimental effects exerted by excessive doses. BIOLOGICAL SIGNIFICANCE: The present work elucidates dose-dependent effects of bLF on the proteomic changes of IECs in vitro supplemented with data from a preterm pig study confirming detrimental effects of enteral feeding with the highest dose of bLF (10g/L). The study contributes to further understanding on mechanisms that bLF, as an important milk protein, can regulate the homeostasis of the immature intestine. Results from this study urge neonatologists to carefully consider the dose of bLF to supplement into infant formula used for preterm neonates. PMID- 26996465 TI - Aetiology and prevalence of post-colonoscopy colorrectal cancer. AB - BACKGROUND: Colonoscopy is the gold standard for the detection and prevention of colorectal cancer (CRC). However, some individuals are diagnosed with CRC soon after a previous colonoscopy. AIMS: To evaluate the rate of new onset or missed CRC after a previous colonoscopy and to study potential risk factors. METHODS: Patients in our endoscopy database diagnosed with CRC from March 2004 to September 2011 were identified, selecting those with a colonoscopy performed within the previous 5years. Medical records included age, gender, comorbidities and colonoscopy indication. Tumour characteristics studied were localization, size, histological grade and TNM stage and possible cause. These patients were compared with those diagnosed with CRC at their first endoscopy (sporadic CRC control group). RESULTS: A total of 712 patients with CRC were included; 24 patients (3.6%) had undergone colonoscopy within the previous 5 years (50% male, 50% female, mean age 72). Post-colonoscopy CRCs were attributed to: 1 (4.2%) incomplete colonoscopy, 4 (16.6%) incomplete polyp removal, 1 (4.2%) failed biopsy, 8 (33.3%) 'missed lesions' and 10 (41.7%) new onset CRC. Post-colonoscopy CRCs were smaller in size than sporadic CRCs (3.2cm vs. 4.5cm, P<.001) and were mainly located in the proximal colon (63% vs. 35%, P=.006); no difference in histological grade was found (P=.125), although there was a tendency towards a lower TNM stage (P=.053). CONCLUSIONS: There is a minor risk of CRC development after a previous colonoscopy (3.6%). Most of these (58.4%) are due to preventable factors. Post-colonoscopy CRCs were smaller and mainly right-sided, with a tendency towards an earlier TNM stage. PMID- 26996466 TI - Advances for improved diagnosis of microscopic colitis in patients with chronic diarrhoea. AB - Microscopic colitis is a generic term that includes 2 main forms, collagenous colitis and lymphocytic colitis, and describes a form of inflammatory bowel disease with a chronic and relapsing course. The incidence of microscopic colitis is between 2 and 8 times higher in women than in men, although age, more than sex, increases the risk of collagenous colitis (odds ratio [OR] 8.3 for age >=65 vs. <65 and OR 2.8 for women). The main symptom is chronic non-bloody watery diarrhoea. Other common symptoms include abdominal pain (50%-70%), with the result that many patients with microscopic colitis meet criteria for irritable bowel syndrome. Colonoscopy with multiple colonic biopsies is currently recommended, as histological changes are the main characteristic feature. The colonic mucosa is macroscopically normal, although certain minimal endoscopic abnormalities have been described. PMID- 26996467 TI - Development of a simple and rapid diagnosis method for swine edema disease to specifically detect Stx2e protein by immunochromatographic test. AB - Edema disease in piglets is caused by Shiga toxin 2e (Stx2e)-producing Escherichia coli. However, there is currently no available Stx2e-specific immunochromatographic test strip to differentiate Stx2e from other types of Shiga toxin 2. In the present study, to develop an Stx2e-specific immunochromatographic test strip, we isolated nine different monoclonal antibody-producing hybridoma clones from Stx2e toxoid-immunized mice and confirmed that six antibodies were A subunit-specific whereas three antibodies were B subunit-specific. Only one A subunit-specific monoclonal antibody (45B2) was cross-reactive with prototype Stx2 (Stx2a) at the same sensitivity, but the remaining eight monoclonal antibodies were not. In immunochromatographic tests using the highly sensitive antibodies, test strips using some combinations of gold colloid-conjugated monoclonal antibody with the B subunit-specific monoclonal antibody on the membrane detected Stx2e, but not other types of Shiga toxin 2. These test strips had the ability to detect Stx2e in the culture supernatant of clinically isolated Stx2e gene-positive strains, but not in those of Stx2e gene-negative strains. These results indicate that our test strip is practical for the specific detection of Stx2e to diagnose swine edema disease. PMID- 26996468 TI - Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD. METHODS: A hospital based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. RESULTS: A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. CONCLUSION: Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD. PMID- 26996469 TI - Very Long-term Outcomes and Predictors of Percutaneous Coronary Intervention with Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Patients with Unprotected Left Main Coronary Artery Disease. AB - BACKGROUND: There are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events. METHODS: All consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups. RESULTS: Nine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3-8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group. CONCLUSIONS: During a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group. PMID- 26996470 TI - Menopausal Symptoms and Sleep Quality During Menopausal Transition and Postmenopause. AB - BACKGROUND: Menopausal symptoms and sleep difficulty were physiological processes that were affected by genetic and other factors. This study was to investigate the prevalence of menopausal symptoms and sleep quality in menopausal transition (MT) and postmenopause (PM) women in Taiyuan, Shanxi. METHODS: A community-based survey of women's menopausal symptoms and sleep quality was conducted between July 2012 and May 2013 at six municipal districts of Taiyuan, Shanxi. A sample of 2429 women aged 40-59 years was divided into four groups: early MT, late MT, early PM, and late PM. Sleep quality in the past 2 weeks before the interview was recorded. The data were analyzed using SPSS 16.0. RESULTS: The prevalence of menopausal symptoms was 49.8%. Mild, moderate, and severe symptoms were observed in 28.9%, 18.5%, and 2.5% of participants, respectively. The highest prevalence of menopausal symptoms occurred in the early postmenopausal stage; the subsequences were the late postmenopausal stage and the early MT stage. Interestingly, among the 13 items of modified Kupperman index, the five most common symptoms were fatigue, arthralgia and myalgia, decreased libido, insomnia, and nervousness. Meanwhile, 55% perimenopausal women had poor sleep. CONCLUSIONS: Menopausal symptoms are common but mild among women in Taiyuan, Shanxi during MT and PM. In these stages, the prevalence of poor sleep is high. PMID- 26996471 TI - Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus. METHODS: This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level. RESULTS: In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 +/- 5.40 years and 9.59 +/- 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37-4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47-38.03), dyslipidemia (OR 2.65, CI 1.54-4.56), diastolic blood pressure (OR 1.02, CI 1.00-1.04), and body mass index (OR 0.95, CI 0.92-0.99) are independent factors for early-onset T2DM. CONCLUSIONS: We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus. PMID- 26996472 TI - Comparison of the Reference Intervals Used for the Evaluation of Maternal Thyroid Function During Pregnancy Using Sequential and Nonsequential Methods. AB - BACKGROUND: Maternal thyroid dysfunction is common during pregnancy, and physiological changes during pregnancy can lead to the overdiagnosis of hyperthyroidism and misdiagnosis of hypothyroidism with nongestation-specific reference intervals. Our aim was to compare sequential with nonsequential methods for the evaluation of thyroid function in pregnant women. METHODS: We tested pregnant women who underwent their trimester prenatal screening at our hospital from February 2011 to September 2012 for serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) using the Abbott and Roche kits. There were 447 and 200 patients enrolled in the nonsequential and sequential groups, respectively. The central 95% range between the 2.5th and the 97.5th percentiles was used as the reference interval for the thyroid function parameter. RESULTS: The nonsequential group exhibited a significantly larger degree of dispersion in the TSH reference interval during the 2nd and 3rd trimesters as measured using both the Abbott and Roche kits (all P < 0.05). The TSH reference intervals were significantly larger in the nonsequential group than in the sequential group during the 3rd trimester as measured with both the Abbott (4.95 vs. 3.77 mU/L, P < 0.001) and Roche kits (6.62 vs. 5.01 mU/L, P = 0.004). The nonsequential group had a significantly larger FT4 reference interval as measured with the Abbott kit during all trimesters (12.64 vs. 5.82 pmol/L; 7.96 vs. 4.77 pmol/L; 8.10 vs. 4.77 pmol/L, respectively, all P < 0.05), whereas a significantly larger FT4 reference interval was only observed during the 2nd trimester with the Roche kit (7.76 vs. 5.52 pmol/L, P = 0.002). CONCLUSIONS: It was more reasonable to establish reference intervals for the evaluation of maternal thyroid function using the sequential method during each trimester of pregnancy. Moreover, the exclusion of pregnancy-related complications should be considered in the inclusion criteria for thyroid function tests. PMID- 26996473 TI - Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. METHODS: We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. RESULTS: The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P = 0.004). The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (>=4.5) were observed exclusively in the ALS patients. CONCLUSIONS: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders. PMID- 26996474 TI - Significance of Vestibular Testing on Distinguishing the Nerve of Origin for Vestibular Schwannoma and Predicting the Preservation of Hearing. AB - BACKGROUND: Determining the nerve of origin for vestibular schwannoma (VS), as a method for predicting hearing prognosis, has not been systematically considered. The vestibular test can be used to investigate the function of the superior vestibular nerve (SVN) and the inferior vestibular nerve (IVN). This study aimed to preoperatively distinguish the nerve of origin for VS patients using the vestibular test, and determine if this correlated with hearing preservation. METHODS: A total of 106 patients with unilateral VS were enrolled in this study prospectively. Each patient received a caloric test, vestibular-evoked myogenic potential (VEMP) test, and cochlear nerve function test (hearing) before the operation and 1 week, 3, and 6 months, postoperatively. All patients underwent surgical removal of the VS using the suboccipital approach. During the operation, the nerve of tumor origin (SVN or IVN) was identified by the surgeon. Tumor size was measured by preoperative magnetic resonance imaging. RESULTS: The nerve of tumor origin could not be unequivocally identified in 38 patients (38/106, 35.80%). These patients were not subsequently evaluated. In 26 patients (nine females, seventeen males), tumors arose from the SVN and in 42 patients (18 females, 24 males), tumors arose from the IVN. Comparing with the nerve of origins (SVN and IVN) of tumors, the results of the caloric tests and VEMP tests were significantly different in tumors originating from the SVN and the IVN in our study. Hearing was preserved in 16 of 26 patients (61.54%) with SVN originating tumors, whereas hearing was preserved in only seven of 42 patients (16.67%) with IVN-originating tumors. CONCLUSIONS: Our data suggest that caloric and VEMP tests might help to identify whether VS tumors originate from the SVN or IVN. These tests could also be used to evaluate the residual function of the nerves after surgery. Using this information, we might better predict the preservation of hearing for patients. PMID- 26996475 TI - Short- and Long-term Outcomes in Patients with Connective Tissue Diseases Undergoing Percutaneous Coronary Intervention. AB - BACKGROUND: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in patients with connective tissue diseases (CTDs). Risk factors and clinical characteristics in these patients are not equivalent to those in traditional CAD patients. The objective of this study was to report short- and long-term clinical outcomes in a consecutive series of patients with CTD who underwent percutaneous coronary intervention (PCI) with stent implantation. METHODS: The study group comprised 106 consecutive patients with CTD who underwent PCI in Beijing Friendship Hospital between January 2009 and June 2012. Medical records were analyzed retrospectively including clinical basic material, coronary angiogram data, and the incidence of major adverse cardiac events (MACEs) during the short- and long-term (median 3 years) follow-up. RESULTS: Ninety-two of the patients (86.8%) had one or more traditional CAD risk factors. Multivessel disease was present in more than 2/3 of patients (73.6%). The left anterior descending coronary artery was the most commonly affected vessel (65.1%). Five bare-metal stents and 202 drug-eluting stents were implanted. After a median follow-up period of 36 months, thirteen patients (12.3%) died from cardiac causes, the rate of stent thrombosis was 9.4%, and the rate of target vessel revascularization (TVR) was 14.2%. Multivariate analysis revealed that hypertension (hazard ratio [HR] = 3.07, 95% confidence interval [CI]: 1.30-7.24, P = 0.041), anterior myocardial infarction (HR = 2.77, 95% CI: 1.06-7.03, P = 0.04), longer duration of steroid treatment (HR = 3.60, 95% CI: 1.43-9.08, P = 0.032), and C-reactive protein level >10 mg/L (HR = 3.98, 95% CI: 1.19-12.56, P = 0.036) were independent predictors of MACEs. CONCLUSIONS: Patients with CTD and CAD may have severe coronary lesions. PCI in these patients tends to result in an increased rate of stent thrombosis and TVR during long-term follow-up, which may be influenced by traditional and nontraditional risk factors. PMID- 26996476 TI - Increased Local Spontaneous Neural Activity in the Left Precuneus Specific to Auditory Verbal Hallucinations of Schizophrenia. AB - BACKGROUND: Auditory verbal hallucinations (AVHs) of schizophrenia have been associated with structural and functional alterations of some brain regions. However, the brain regional homogeneity (ReHo) alterations specific to AVHs of schizophrenia remain unclear. In the current study, we aimed to investigate ReHo alterations specific to schizophrenic AVHs. METHODS: Thirty-five schizophrenic patients with AVH, 41 schizophrenic patients without AVHs, and fifty healthy subjects underwent resting-state functional magnetic resonance imaging. ReHo differences across the three groups were tested using a voxel-wise analysis. RESULTS: Compared with the healthy control group, the two schizophrenia groups showed significantly increased ReHo in the right caudate and inferior temporal gyrus and decreased ReHo in the bilateral postcentral gyrus and thalamus and the right inferior occipital gyrus (false discovery rate corrected, P < 0.05). More importantly, the AVH group exhibited significantly increased ReHo in the left precuneus compared with the non-AVH group. However, using correlation analysis, we did not find any correlation between the auditory hallucination rating scale score and the ReHo of brain regions. CONCLUSIONS: Our results suggest that increased ReHo in the left precuneus may be a pathological feature exclusive to schizophrenic AVHs. PMID- 26996477 TI - Patient Trust in Physicians: Empirical Evidence from Shanghai, China. AB - BACKGROUND: Patient trust in physicians, which can be considered a collective good, is necessary for an effective health care system. However, there is a widespread concern that patient trust in physicians is declining under various threats to the physician-patient relationship worldwide. This article aimed to assess patient trust in physicians through a quantitative study in Shanghai, China, and to provide appropriate suggestions for improving the trust in China. METHODS: The data from a survey conducted in Zhongshan Hospital and Shanghai Tenth People's Hospital, which are two tertiary public hospitals in Shanghai, were used in this study. Patient trust in physicians was the dependent variable. Furthermore, a 10-item scale was used to precisely describe the dependent variable. The demographic characteristics were independent variables of trust in physicians. Binomial logistic regression was employed to analyze the factors associated with the dependent variable, which was divided into two categories on the basis of the responses (1: Strongly agree or agree and 0: Strongly disagree, disagree, or neutral). RESULTS: This study found that 67% of patients trusted or strongly trusted physicians. The mean score of patient trust in physicians was 35.4 from a total score of 50. Furthermore, patient trust in physicians was significantly correlated with the age, education level, annual income, and health insurance coverage of the patients. CONCLUSIONS: Patient trust in physicians in Shanghai, China is higher than previously reported. Furthermore, the most crucial reason for patient distrust in physicians is the information asymmetry between patients and physicians, which is a natural property of the physician-patient relationship, rather than the so-called for-profit characteristic of physicians or patients' excessive expectations. PMID- 26996478 TI - Effect of Inhaled Budesonide on Interleukin-4 and Interleukin-6 in Exhaled Breath Condensate of Asthmatic Patients. AB - BACKGROUND: Studies of interleukin (IL)-4 and IL-6 in the exhaled breath condensate (EBC) of asthmatic patients are limited. This study was to determine the effect of inhaled corticosteroid (ICS) treatment on IL-4 and IL-6 in the EBC of asthmatic patients. METHODS: In a prospective, open-label study, budesonide 200 MUg twice daily by dry powder inhaler was administered to 23 adult patients with uncontrolled asthma (mean age 42.7 years) for 12 weeks. Changes in asthma scores, lung function parameters (forced expiratory volume in 1 s [FEV1], peak expiratory flow [PEF], forced expiratory flow at 50% of forced vital capacity [FEF50], forced expiratory flow at 75% of forced vital capacity, maximum mid expiratory flow rate) and the concentrations of IL-4 and IL-6 in EBC were measured. RESULTS: Both asthma scores and lung function parameters were significantly improved by ICS treatment. The mean IL-4 concentration in the EBC was decreased gradually, from 1.92 +/- 0.56 pmol/L before treatment to 1.60 +/- 0.36 pmol/L after 8 weeks of treatment (P < 0.05) and 1.54 +/- 0.81 pmol/L after 12 weeks of treatment (P < 0.01). However, the IL-6 concentration was not significantly decreased. The change in the IL-4 concentration was correlated with improvements in mean FEV1, PEF and FEF50 values (correlation coefficients -0.468, -0.478, and -0.426, respectively). CONCLUSIONS: The concentration of IL-4 in the EBC of asthmatic patients decreased gradually with ICS treatment. Measurement of IL-4 in EBC could be useful to monitor airway inflammation in asthmatics. PMID- 26996479 TI - Effect of Resveratrol on Preventing Steroid-induced Osteonecrosis in a Rabbit Model. AB - BACKGROUND: Prevention of osteonecrosis (ON) has seldom been addressed. The purpose of this study was to evaluate the effect of resveratrol on preventing steroid-induced ON in rabbits. METHODS: Seventy-two rabbits were divided into four groups: (1) NEC (ON) group: thirty rabbits were treated with lipopolysaccharide (LPS) once, then with methylprednisolone (MPS) daily for 3 days; (2) PRE (prevention) group: thirty rabbits were given one dose of LPS, then MPS daily for 3 days, and resveratrol on day 0 and daily for 2 weeks; (3) RES (resveratrol) group: six rabbits were given resveratrol for 2 weeks but without LPS/MPS; (4) CON (control) group: six rabbits were given alcohol for 2 weeks but without LPS/MPS. Levels of plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), thrombomodulin (TM), vascular endothelial growth factor (VEGF), maximum enhancement (ME) by magnetic resonance imaging, and ON incidence were evaluated. RESULTS: The PRE group had a lower ON incidence than the NEC group, but with no significant differences at 2 weeks and 12 weeks. The RES and CON groups did not develop ON. TM and VEGF were significantly higher in the NEC group compared with the PRE group at weeks 1, 2, and 4 (TM: 1 week, P = 0.029; 2 weeks, P = 0.005; and 4 weeks, P = 0.047; VEGF: 1 week, P = 0.039; 2 weeks, P = 0.021; 4 weeks, P = 0.014), but the difference disappeared at 12 weeks. The levels of t-PA and PAI-1 were not significantly different between the NEC and PRE groups. The TM, t-PA, PAI-1, and VEGF concentrations in the RES and CON groups did not change over time. Compared to the baseline, ME in the NEC group decreased significantly (P = 0.025) at week 1, increased significantly (P = 0.021) at week 2, and was decreased at week 12. The variance was insignificant in the PRE group. CONCLUSIONS: Resveratrol may improve blood supply to bone in a rabbit model of ON of the femoral head via anti inflammatory effects to protect the vascular endothelium and reduce thrombosis. PMID- 26996480 TI - Could Intrathymic Injection of Myelin Basic Protein Suppress Inflammatory Response After Co-culture of T Lymphocytes and BV-2 Microglia Cells? AB - BACKGROUND: The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV 2 microglia cells. METHODS: Totally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 MUl MBP (1 mg/ml); Group B: intrathymic injection of 100 MUl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro inflammatory factors of BV-2 microglia cells (interleukin [IL]-1beta, tumor necrosis factor-alpha [TNF-alpha], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis. RESULTS: The levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 +/ 0.71%, 30.71 +/- 1.14%, 13.50 +/- 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3rd to 7th day, with an upward trend from the 7th to 14th day (10.00 +/- 0.23%, 5.28 +/- 0.69%, 14.67 +/- 2.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The ratio of CD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P < 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45: 83.39 +/- 2.56%, 82.74 +/- 2.09%, 87.56 +/- 2.11%; CD54: 3.80 +/- 0.24%, 0.94 +/- 0.40%, 3.41 +/- 0.33% at postoperative days 3, 7, and 14, respectively, P < 0.05). The expressions of TNF-alpha, IL-1beta, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P < 0.05). No significant difference was found between Groups B and C. CONCLUSIONS: Intrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response. PMID- 26996481 TI - Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia: Focus on Glycogen Synthase Kinase-3beta and beta-catenin. AB - BACKGROUND: Cognitive impairment is a severe complication caused by obstructive sleep apnea (OSA). The mechanisms of causation are still unclear. The Wnt/beta catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wnt/beta-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological component of OSA. METHODS: We divided 32 4 week-old male C57/BL mice into four groups of eight each: a CIH + normal saline (NS) group, CIH + LiCl group, sham CIH + NS group, and a sham CIH + LiCl group. The spatial learning performance of each group was assessed by using the Morris water maze (MWM). Protein expressions of glycogen synthase kinase-3beta (GSK 3beta) and beta-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. RESULTS: Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-3beta activity increased, and expression of beta-catenin decreased significantly in the hippocampus of the CIH exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCl decreased the activity of GSK-3beta and increased the expression of beta-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. CONCLUSIONS: Wnt/beta-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive impairment via Wnt/beta catenin signaling pathway. PMID- 26996482 TI - Effects of Saikokaryukotsuboreito on Spermatogenesis and Fertility in Aging Male Mice. AB - BACKGROUND: Aspermia caused by exogenous testosterone limit its usage in late onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice. METHODS: Thirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed. RESULTS: In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 +/- 12.31 ng/g vs. 74.10 +/- 11.45 ng/g, P = 0.027; sperm number: [14.94 +/- 4.63] * 106 cells/ml vs. [8.79 +/- 4.38] * 106 cells/ml, P = 0.002; sperm motility: 43.16 +/- 9.93% vs. 33.51 +/- 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 +/- 11.01 ng/ml vs. 49.30 +/- 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 +/- 0.09 vs. 0.84 +/- 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 +/- 8.67, P = 0.005; sperm number: [4.34 +/- 2.45] * 106 cells/ml, P = 0.018; sperm motility: 19.53 +/- 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 +/- 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 +/- 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 +/- 0.09, P < 0.001), and fertility was also suppressed (P < 0.05, respectively). CONCLUSION: SKRBT had no adverse effect on fertility potential in aging male mice. PMID- 26996485 TI - Flexible Subclavian Artery Closure for an Inadvertent Injury to the Internal Mammary Artery During Internal Jugular Vein Catheterization. PMID- 26996483 TI - Single Nucleotide Polymorphism rs10919543 in FCGR2A/FCGR3A Region Confers Susceptibility to Takayasu Arteritis in Chinese Population. AB - BACKGROUND: Takayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. METHODS: Four single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. RESULTS: Among the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 - 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] *109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] *109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed. CONCLUSIONS: Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA. PMID- 26996484 TI - Targeted Genes Sequencing Identified a Novel 15 bp Deletion on GJA8 in a Chinese Family with Autosomal Dominant Congenital Cataracts. AB - BACKGROUND: Congenital cataract (CC) is the leading cause of visual impairment or blindness in children worldwide. Because of highly genetic and clinical heterogeneity, a molecular diagnosis of the lens disease remains a challenge. METHODS: In this study, we tested a three-generation Chinese family with autosomal dominant CCs by targeted sequencing of 45 CC genes on next generation sequencing and evaluated the pathogenicity of the detected mutation by protein structure, pedigree validation, and molecular dynamics (MD) simulation. RESULTS: A novel 15 bp deletion on GJA8 (c.426_440delGCTGGAGGGGACCCT or p. 143_147delLEGTL) was detected in the family. The deletion, concerned with an in frame deletion of 5 amino acid residues in a highly evolutionarily conserved region within the cytoplasmic loop domain of the gap junction channel protein connexin 50 (Cx50), was in full cosegregation with the cataract phenotypes in the family but not found in 1100 control exomes. MD simulation revealed that the introduction of the deletion destabilized the Cx50 gap junction channel, indicating the deletion as a dominant-negative mutation. CONCLUSIONS: The above results support the pathogenic role of the 15 bp deletion on GJA8 in the Chinese family and demonstrate targeted genes sequencing as a resolution to molecular diagnosis of CCs. PMID- 26996486 TI - Remission of Refractory Membranous Nephropathy by Low-dose Rituximab: A Case Report. PMID- 26996487 TI - Clinical Features and Neuroimaging Findings in Patients with Cerebral Fat Embolism. PMID- 26996488 TI - Tramadol Pill Alone May Cause Serotonin Syndrome. PMID- 26996489 TI - Partial Remission of Hepatic Metastatic Lesion but Complicated with Secondary and Refractory Fever Lead by Nivolumab in a Patient with Lung Adenocarcinoma Presenting Gefitinib Acquired Resistance. PMID- 26996490 TI - Diffuse Type Tenosynovial Giant Cell Tumor of the Ankle. PMID- 26996491 TI - Aggregation-induced emission of diarylamino-pi-carborane triads: effects of charge transfer and pi-conjugation. AB - Carborane-based donor-pi-acceptor triads (D-pi-A-pi-D) bearing triarylamine moieties were synthesised. All the monomeric triads showed a blue-green emission in a dilute solution, which was assigned as an intramolecular charge-transfer (CT) emission. The intramolecular CT emission showed large Stokes shifts at a higher solvent polarity. The intramolecular CT emission further shifted to a longer wavelength with the increase in pi-conjugation. Interestingly, a strong red emission was observed in highly concentrated solutions or in the solid state, which was assigned as an aggregation-induced emission (AIE). Moreover, the AIE strongly depended on solvent polarity. A large Stokes shift in AIE was attributed to the strong CT character. The changes in the dipole moment for the AIE state and monomer emission were evaluated using the Lippert-Mataga relationship. The density functional theory calculations showed that the change in electron distribution between the aryl amino group (highest occupied molecular orbital, HOMO) and the carborane moiety (lowest unoccupied molecular orbital, LUMO) indicates the intramolecular CT character, and the emission colour changes were attributed to the HOMO-LUMO energy gap controlled by the pi-extension of the phenylene linker. The electrochemical properties such as oxidation and reduction potentials were consistent with theoretical calculation results. The emission properties were affected by two main factors: solvent polarity and solubility. PMID- 26996492 TI - Bleeding risk assessment and comorbidities in elderly patients with acute coronary syndromes. PMID- 26996493 TI - Special Issue on "Toxins: New targets and new functions". PMID- 26996494 TI - Bradykinin in Hemipepsis ustulata: A novel method for safely milking wasps. AB - Wasp venom characterization is of interest across multiple disciplines such as medicinal chemistry and evolutionary biology. A simple method is described herein to milk wasp venom without undue risks to the researcher. The wasps were immobilized by cooling for safe handling, restrained, and their venom was collected on parafilm. Bradykinin from Hemipepsis ustulata was identified by LC MS/MS during method verification. PMID- 26996495 TI - Biochemical and functional studies of ColTx-I, a new myotoxic phospholipase A2 isolated from Crotalus oreganus lutosus (Great Basin rattlesnake) snake venom. AB - Commonly, phospholipases A2 (PLA2s) play key roles in the pathogenesis of the local tissue damage characteristic of crotaline and viperine snake envenomations. Crotalus oreganus lutosus snake venom has not been extensively studied; therefore, the characterization of its components represents a valuable biotechnological tool for studying pathophysiological processes of envenoming and for gaining a deeper understanding of its biological effects. In this study, for the first time, a basic PLA2 myotoxin, ColTx-I, was purified from C. o. lutosus through two chromatographic steps. ColTx-I is monomeric with calculated molecular mass weight (Mw) of 14,145 Da and a primary structure closely related to basic PLA2s from viperid venoms. The pure enzyme has a specific activity of 15.87 +/- 0.65 nmol/min/mg at optimal conditions (pH 8.0 and 37 degrees C). ColTx-I activity was found to be dependent on Ca(2+), as its substitution by other ionic species as well as the addition of chelating agents significantly reduced its phospholipase activity. In vivo, ColTx-I triggered dose-dependent inflammatory responses, measured using the paw edema model, with an increase in IL-6 levels, systemic and local myotoxicity, characterized by elevated plasma creatine kinase activity. ColTx-I induced a complex series of degenerative events associated with edema, inflammatory infiltrate and skeletal muscle necrosis. These biochemical and functional results suggest that ColTx-I, a myotoxic and inflammatory mediator, plays a relevant role in C. o. lutosus envenomation. Thus, detailed studies on its mechanism of action, such as evaluating the synergism between ColTx-I and other venom components may reveal targets for the development of more specific and effective therapies. PMID- 26996500 TI - Beneficial effect of antidepressants against rotenone induced Parkinsonism like symptoms in rats. AB - Parkinson's disease is a second most common age-related neurodegenerative disorder characterized by the loss of DA neurons of SNpc region of the midbrain. Neurotransmitter dysfunction is involved in the pathogenesis of PD. Antidepressants like venlafaxine and sertraline expected to improve Parkinsonism like symptoms by modulating the levels of various neurotransmitters. The neuroprotective role of antidepressants is well explored in various CNS disorders. Therefore, this study was designed to explore and compare the mechanistic role of different antidepressants (venlafaxine and sertraline) against rotenone induced Parkinsonism like symptoms in rats. Rats were administrated with rotenone (1.5mg/kg/day; s.c.) daily for a period of 28 days. Venlafaxine (10 and 20mg/kg; p.o.), sertraline (10 and 20mg/kg; p.o.) and Levodopa combination with Carbidopa (10mg/kg; p.o.) were administered daily starting from 7th day one hour prior to rotenone administration. Behavioral parameters (body weight, rotarod, grip strength, narrow beam walk and open field) were assessed on weekly basis. On 28th day, animals were sacrificed and striatum were isolated for biochemical (LPO, GSH and nitrite), neuroinflammatory (TNF alpha, IL-1beta and IL-6), neurochemical (DA, NE, 5-HT, GABA, Glutamate, DOPAC, HVA and 5-HIAA) and mitochondrial complex-I estimation. Rotenone administration significantly reduced body weight, motor coordination, oxidative defense, increased pro-inflammatory mediators and decreased level of catecholamines. Pre treatment with venlafaxine and sertraline significantly attenuated the alteration in behavioral, oxidative stress, neuroinflammatory, mitochondrial and catecholamines level in striatum. The study provides a hope that these drugs could be used as adjuvant therapy in the management and treatment of PD. PMID- 26996496 TI - Optimal extent of lymphadenectomy for gastric adenocarcinoma: A 7-institution study of the U.S. gastric cancer collaborative. AB - BACKGROUND AND OBJECTIVES: The optimal extent of lymphadenectomy in the treatment of gastric adenocarcinoma is debated. We compared gastrectomy outcomes following limited (D1) or extended (D2) lymphadenectomy. METHODS: Using the multi institutional US Gastric Cancer Collaborative database, we reviewed the morbidity, mortality, recurrence, and overall survival (OS) of patients receiving D1 or D2 lymphadenectomies. RESULTS: Between 2000 and 2012, 266 and 461 patients received a D1 and D2 lymphadenectomy, respectively. ASA class, mean number of comorbidities, grade, and stage were similar between groups. While major morbidity was similar (P = 0.85), mortality was worse for those receiving a D1 lymphadenectomy (4.9% vs. 1.3%, P = 0.004). D2 lymphadenectomy was associated with improved median OS in stage I (4.7 years for D1 vs. not reached for D2, P = 0.003), stage II (3.6 years for D1 vs. 6.3 for D2, P = 0.42), and stage III patients (1.3 years for D1 vs. 2.1 for D2, P = 0.01). After adjusting for predictors of OS, D2 lymphadenectomy remained a significant predictor of improved survival (HR 1.5, 95%CI 1.1-2.0, P = 0.008). CONCLUSIONS: D2 lymphadenectomy can be performed without increased risk of morbidity and mortality. Additionally, D2 lymphadenectomy is associated with improved survival especially in early stages, and should be considered for gastric adenocarcinoma patients. J. Surg. Oncol. 2016;113:750-755. (c) 2016 Wiley Periodicals, Inc. PMID- 26996501 TI - Neural Correlates of Decision Thresholds in the Human Subthalamic Nucleus. AB - If humans are faced with difficult choices when making decisions, the ability to slow down responses becomes critical in order to avoid suboptimal choices. Current models of decision making assume that the subthalamic nucleus (STN) mediates this function by elevating decision thresholds, thereby requiring more evidence to be accumulated before responding [1-9]. However, direct electrophysiological evidence for the exact role of STN during adjustment of decision thresholds is lacking. Here, we show that trial-by-trial variations in STN low-frequency oscillatory activity predict adjustments of decision thresholds before subjects make a response. The relationship between STN activity and decision thresholds critically depends on the subjects' level of cautiousness. While increased oscillatory activity of the STN predicts elevated decision thresholds during high levels of cautiousness, it predicts decreased decision thresholds during low levels of cautiousness. This context-dependent relationship may be mediated by increased influence of the medial prefrontal cortex (mPFC)-STN pathway on decision thresholds during high cautiousness. Subjects who exhibit a stronger increase in phase alignment of low-frequency oscillatory activity in mPFC and STN before making a response have higher decision thresholds and commit fewer erroneous responses. Together, our results demonstrate that STN low frequency oscillatory activity and corresponding mPFC-STN coupling are involved in determining how much evidence subjects accumulate before making a decision. This finding might explain why deep-brain stimulation of the STN can impair subjects' ability to slow down responses and can induce impulsive suboptimal decisions. PMID- 26996502 TI - The INDETERMINATE DOMAIN Protein BROAD LEAF1 Limits Barley Leaf Width by Restricting Lateral Proliferation. AB - Variation in the size, shape, and positioning of leaves as the major photosynthetic organs strongly impacts crop yield, and optimizing these aspects is a central aim of cereal breeding [1, 2]. Leaf growth in grasses is driven by cell proliferation and cell expansion in a basal growth zone [3]. Although several factors influencing final leaf size and shape have been identified from rice and maize [4-14], what limits grass leaf growth in the longitudinal or transverse directions during leaf development remains poorly understood. To identify factors involved in this process, we characterized the barley mutant broad leaf1 (blf1). Mutants form wider but slightly shorter leaves due to changes in the numbers of longitudinal cell files and of cells along the leaf length. These differences arise during primordia outgrowth because of more cell divisions in the width direction increasing the number of cell files. Positional cloning, analysis of independent alleles, and transgenic complementation confirm that BLF1 encodes a presumed transcriptional regulator of the INDETERMINATE DOMAIN family. In contrast to loss-of-function mutants, moderate overexpression of BLF1 decreases leaf width below wild-type levels. A functional BLF1-vYFP fusion protein expressed from the endogenous promoter shows a dynamic expression pattern in the shoot apical meristem and young leaf primordia. Thus, we propose that the BLF1 gene regulates barley leaf size by restricting cell proliferation in the leaf-width direction. Given the agronomic importance of canopy traits in cereals, identifying functionally different BLF1 alleles promises to allow for the generation of optimized cereal ideotypes. PMID- 26996503 TI - High Resilience of Seed Dispersal Webs Highlighted by the Experimental Removal of the Dominant Disperser. AB - The pressing need to conserve and restore habitats in the face of ongoing species loss [1, 2] requires a better understanding of what happens to communities when species are lost or reinstated [3, 4]. Theoretical models show that communities are relatively insensitive to species loss [5, 6]; however, they disagree with field manipulations showing a cascade of extinctions [7, 8] and have seldom been tested under field conditions (e.g., [9]). We experimentally removed the most abundant seed-dispersing ant species from seed dispersal networks in a Mediterranean landscape, replicating the experiment in three types of habitat, and then compared these communities to un-manipulated control communities. Removal did not result in large-scale changes in network structure. It revealed extensive structural plasticity of the remaining community, which rearranged itself through rewiring, while maintaining its functionality. The remaining ant species widened their diet breadth in a way that maintained seed dispersal, despite the identity of many interactions changing. The species interaction strength decreased; thus, the importance of each ant species for seed dispersal became more homogeneous, thereby reducing the dependence of seed species on one dominant ant species. Compared to the experimental results, a simulation model that included rewiring considerably overestimated the effect of species loss on network robustness. If community-level species loss models are to be of practical use in ecology or conservation, they need to include behavioral and population responses, and they need to be routinely tested under field conditions; doing this would be to the advantage of both empiricists and theoreticians. PMID- 26996504 TI - Crossmodal Association of Visual and Haptic Material Properties of Objects in the Monkey Ventral Visual Cortex. AB - Just by looking at an object, we can recognize its non-visual properties, such as hardness. The visual recognition of non-visual object properties is generally accurate [1], and influences actions toward the object [2]. Recent studies suggest that, in the primate brain, this may involve the ventral visual cortex, which represents objects in a way that reflects not only visual but also non visual object properties, such as haptic roughness, hardness, and weight [3-7]. This new insight raises a fundamental question: how does the visual cortex come to represent non-visual properties--knowledge that cannot be acquired directly through vision? Here we addressed this unresolved question using fMRI in macaque monkeys. Specifically, we explored whether and how simple visuo-haptic experience -just seeing and touching objects made of various materials--can shape representational content in the visual cortex. We measured brain activity evoked by viewing images of objects before and after the monkeys acquired the visuo haptic experience and decoded the representational space from the activity patterns [8]. We show that simple long-term visuo-haptic experience greatly impacts representation in the posterior inferior temporal cortex, the higher ventral visual cortex. After the experience, but not before, the activity pattern in this region well reflected the haptic material properties of the experienced objects. Our results suggest that neural representation of non-visual object properties in the visual cortex emerges through long-term crossmodal exposure to objects. This highlights the importance of unsupervised learning of crossmodal associations through everyday experience [9-12] for shaping representation in the visual cortex. PMID- 26996505 TI - The Hippo Pathway Regulates Neuroblasts and Brain Size in Drosophila melanogaster. AB - A key question in developmental neurobiology is how neural stem cells regulate their proliferative potential and cellular diversity and thus specify the overall size of the brain. Drosophila melanogaster neural stem cells (neuroblasts) are known to regulate their ability to self-renew by asymmetric cell division and produce different types of neurons and glia through sequential expression of temporal transcription factors [1]. Here, we show that the conserved Hippo pathway, a key regulator of epithelial organ size [2-4], restricts neuroblast proliferative potential and neuronal cell number to regulate brain size. The inhibition of Hippo pathway activity via depletion of the core kinases Tao-1, Hippo, or Warts regulates several key characteristics of neuroblasts during postembryonic neurogenesis. The Hippo pathway is required to maintain timely entry and exit from neurogenesis by regulating both neuroblast reactivation from quiescence and the time at which neuroblasts undergo terminal differentiation. Further, it restricts neuroblast cell-cycle speed, specifies cell size, and alters the proportion of neuron types generated during postembryonic neurogenesis. Collectively, deregulation of Hippo signaling in neuroblasts causes a substantial increase in overall brain size. We show that these effects are mediated via the key downstream transcription co-activator Yorkie and that, indeed, Yorkie overexpression in neuroblasts is sufficient to cause brain overgrowth. These studies reveal a novel mechanism that controls stem cell proliferative potential during postembryonic neurogenesis to regulate brain size. PMID- 26996506 TI - Fungal Biomineralization of Manganese as a Novel Source of Electrochemical Materials. AB - Electrical energy storage systems such as rechargeable lithium-ion batteries (LiBs) and supercapacitors have shown great promise as sustainable energy storage systems [1-4]. However, LiBs have high specific energy density (energy stored per unit mass) and act as slow, steady suppliers for large energy demands. In contrast, supercapacitors possess high specific power (energy transferred per unit mass per unit time) and can charge and discharge quickly for low energy demands. In LiBs, graphite is the most common anode material, although high electrolyte sensitivity and low charge capacity can limit performance. Efforts have been made to improve LiB or supercapacitor performance using alternative electrode materials such as carbon nanotubes and manganese oxides (MnxOy) [3, 5 14]. Microorganisms play significant roles in metal and mineral biotransformations [15-22]. Fungi possess various biomineralization properties, as well as a filamentous mycelium, which may provide mechanical support for mineral deposition. Although some research has been carried out on the application of biological materials as carbon precursors [8, 9, 23], biomineralizing fungal systems have not been investigated. In this research, novel electrochemical materials have been synthesized using a fungal Mn biomineralization process based on urease-mediated Mn carbonate bioprecipitation [24]. The carbonized fungal biomass-mineral composite (MycMnOx/C) showed a high specific capacitance (>350 F g(-1)) in a supercapacitor and excellent cycling stability (>90% capacity was retained after 200 cycles) in LiBs. This is the first demonstration of the synthesis of electrode materials using a fungal biomineralization process, thus providing a novel strategy for the preparation of sustainable electrochemical materials. PMID- 26996508 TI - Individual Identifiability Predicts Population Identifiability in Forensic Microsatellite Markers. AB - Highly polymorphic genetic markers with significant potential for distinguishing individual identity are used as a standard tool in forensic testing [1, 2]. At the same time, population-genetic studies have suggested that genetically diverse markers with high individual identifiability also confer information about genetic ancestry [3-6]. The dual influence of polymorphism levels on ancestry inference and forensic desirability suggests that forensically useful marker sets with high levels of individual identifiability might also possess substantial ancestry information. We study a standard forensic marker set-the 13 CODIS loci used in the United States and elsewhere [2, 7-9]-together with 779 additional microsatellites [10], using direct population structure inference to test whether markers with substantial individual identifiability also produce considerable information about ancestry. Despite having been selected for individual identification and not for ancestry inference [11], the CODIS markers generate nontrivial model-based clustering patterns similar to those of other sets of 13 tetranucleotide microsatellites. Although the CODIS markers have relatively low values of the F(ST) divergence statistic, their high heterozygosities produce greater ancestry inference potential than is possessed by less heterozygous marker sets. More generally, we observe that marker sets with greater individual identifiability also tend toward greater population identifiability. We conclude that population identifiability regularly follows as a byproduct of the use of highly polymorphic forensic markers. Our findings have implications for the design of new forensic marker sets and for evaluations of the extent to which individual characteristics beyond identification might be predicted from current and future forensic data. PMID- 26996507 TI - A Neural Basis for Control of Cichlid Female Reproductive Behavior by Prostaglandin F2alpha. AB - In most species, females time reproduction to coincide with fertility. Thus, identifying factors that signal fertility to the brain can provide access to neural circuits that control sexual behaviors. In vertebrates, levels of key signaling molecules rise at the time of fertility to prime the brain for reproductive behavior [1-11], but how and where they regulate neural circuits is not known [12, 13]. Specifically, 17alpha,20beta-dihydroxyprogesterone (DHP) and prostaglandin F2alpha (PGF2alpha) levels rise in teleost fish around the time of ovulation [10, 14, 15]. In an African cichlid fish, Astatotilapia burtoni, fertile females select a mate and perform a stereotyped spawning routine, offering quantifiable behavioral outputs of neural circuits. We show that, within minutes, PGF2alpha injection activates a naturalistic pattern of sexual behavior in female A. burtoni. We also identify cells in the brain that transduce the prostaglandin signal to mate and show that the gonadal steroid DHP modulates mRNA levels of the putative receptor for PGF2alpha (Ptgfr). We use CRISPR/Cas9 to generate the first targeted gene mutation in A. burtoni and show that Ptgfr is necessary for the initiation of sexual behavior, uncoupling sexual behavior from reproductive status. Our findings are consistent with a model in which PGF2alpha communicates fertility status via Ptgfr to circuits in the brain that drive female sexual behavior. Our targeted genome modification in a cichlid fish shows that dissection of gene function can reveal basic control mechanisms for behaviors in this large family of species with diverse and fascinating social systems [16, 17]. PMID- 26996511 TI - Orbitofrontal cortex reflects changes in response-outcome contingencies during probabilistic reversal learning. AB - In a continuously changing environment, in which behavioral outcomes are rarely certain, animals must be able to learn to integrate feedback from their choices over time and adapt to changing reward contingencies to maintain flexible behavior. The orbitofrontal region of prefrontal cortex (OFC) has been widely implicated as playing a role in the ability to flexibly control behavior. We used a probabilistic reversal learning task to measure rats' behavioral flexibility and its neural basis in the activity of single neurons in OFC. In this task, one lever, designated as 'correct', was rewarded at a high probability (80%) and a second, spatially distinct lever, designated as 'incorrect', was rewarded at a low probability (20%). Once rats reached a learning criterion for reliably selecting the correct lever, reward contingencies of the two levers were switched, and daily sessions were conducted until rats reliably selected the new correct lever. All rats performed the initial Acquisition and subsequent Reversal successfully, with more sessions needed to learn the Reversal. OFC neurons were recorded during five behavioral sessions spanning Acquisition and Reversal learning. The dominant pattern of neural responding in OFC, identified by principal component analysis of the population of neurons recorded, was modulated by reward outcome across behavioral sessions. Generally, activity was higher following rewarded choices than unrewarded. However, there was a correlation between reduced responses to reward following incorrect choices and the establishment of the preference for the correct lever. These results show how signaling by individual OFC neurons may participate in the flexible adaptation of behavior under changing reward contingencies. PMID- 26996509 TI - Extracellular matrix hyaluronan signals via its CD44 receptor in the increased responsiveness to mechanical stimulation. AB - We propose that the extracellular matrix (ECM) signals CD44, a hyaluronan receptor, to increase the responsiveness to mechanical stimulation in the rat hind paw. We report that intradermal injection of hyaluronidase induces mechanical hyperalgesia, that is inhibited by co-administration of a CD44 receptor antagonist, A5G27. The intradermal injection of low (LMWH) but not high (HMWH) molecular weight hyaluronan also induces mechanical hyperalgesia, an effect that was attenuated by pretreatment with HMWH or A5G27. Pretreatment with HMWH also attenuated the hyperalgesia induced by hyaluronidase. Similarly, intradermal injection of A6, a CD44 receptor agonist, produced hyperalgesia that was inhibited by HMWH and A5G27. Inhibitors of protein kinase A (PKA) and Src, but not protein kinase C (PKC), significantly attenuated the hyperalgesia induced by both A6 and LMWH. Finally, to determine if CD44 receptor signaling is involved in a preclinical model of inflammatory pain, we evaluated the effect of A5G27 and HMWH on the mechanical hyperalgesia associated with the inflammation induced by carrageenan. Both A5G27 and HMWH attenuated carrageenan-induced mechanical hyperalgesia. Thus, while LMWH acts at its cognate receptor, CD44, to induce mechanical hyperalgesia, HMWH acts at the same receptor as an antagonist. That the local administration of HMWH or A5G27 inhibits carrageenan-induced hyperalgesia supports the suggestion that carrageenan produces changes in the ECM that contributes to inflammatory pain. These studies define a clinically relevant role for signaling by the hyaluronan receptor, CD44, in increased responsiveness to mechanical stimulation. PMID- 26996512 TI - Partner Selection for People with Intellectual Disabilities. AB - BACKGROUND: The aim of this research was to understand the characteristics that adults with intellectual disabilities look for in a partner. There have been numerous studies that have explored partner selection for people without intellectual disabilities, but no research that specifically identified the traits valued in a partner by people with intellectual disabilities. METHOD: In depth interviews were conducted with eleven participants across two UK sites. All participants were adults with an intellectual disability who had been in a relationship with a partner for over a year. The narratives were analysed utilizing hermeneutic phenomenology, guided by the theory of Van Manen (1990). RESULTS: The findings highlighted that, regardless of age, participant's relationships typically developed within a segregated environment for people with intellectual disabilities over the past 10 years. People with intellectual disabilities expressed a wish to be loved, to be treated kindly and to have companionship. However, they did not place high value on attributes such as financial security, social status or intelligence. CONCLUSIONS: The research demonstrated how poorly integrated people with intellectual disabilities are within mainstream society. Desired characteristics and expectations for participant's relationships were rooted in a shared history and culture, which was shaped by their intellectual disability and support needs. PMID- 26996513 TI - Antibacterial and antifungal potential of Ga-bioactive glass and Ga-bioactive glass/polymeric hydrogel composites. AB - A bioactive glass series (0.42SiO2 -0.10Na2 O-0.08CaO-(0.40 - x)ZnO-(x)Ga2 O3 ) was synthesized, and it is efficacy against the Gram (-ve) bacteria Escherichia coli (E. coli), the Gram (+ve) bacteria Staphylococcus aureus (S. aureus), and the fungus Candida albicans (C. albicans), were characterized through liquid broth analysis. The glass series was also seeded in CMC-Dex hydrogels at three different loadings (0.05, 0.10, and 0.25 m2 ), and the antibacterial and antifungal efficacies of the resulting composites were characterized using both liquid broth and agar diffusion analysis. Liquid broth analysis was conducted using liquid extracts, which for glass samples were obtained after incubation for up to 30 days in both ultrapure water and phosphate buffered saline (PBS), while glass-hydrogel extracts were obtained solely in PBS. Glass extracts (water) decreased C. albicans viability, while those obtained in PBS decreased the viability of both E. coli and C. albicans. Glass-hydrogel extracts exhibited slight inhibition of E. coli and C. albicans. However, none of the liquid extracts decreased S. aureus viability. Glass-hydrogel composites produced inhibition zones in all three microbial cultures, with the greatest efficacy against C. albicans. The results of this study suggest these materials have potential as bone void-filling materials which display antifungal, and possibly, antibacterial properties. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1102-1113, 2017. PMID- 26996510 TI - Neonatal binge alcohol exposure increases microglial activation in the developing rat hippocampus. AB - Aberrant activation of the developing immune system can have long-term negative consequences on cognition and behavior. Teratogens, such as alcohol, activate microglia, the brain's resident immune cells, which could contribute to the lifelong deficits in learning and memory observed in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. The current study investigates the microglial response of the brain 24 h following neonatal alcohol exposure (postnatal days (PDs) 4-9, 5.25 g/kg/day). On PD10, microglial cell counts and area of cell territory were assessed using unbiased stereology in the hippocampal subfields CA1, CA3 and dentate gyrus (DG), and hippocampal expression of pro- and anti-inflammatory genes was analyzed. A significant decrease in microglial cell counts in CA1 and DG was found in alcohol-exposed and sham intubated (SI) animals compared to undisturbed suckle controls (SCs), suggesting overlapping effects of alcohol exposure and intubation alone on the neuroimmune response. Cell territory was decreased in alcohol-exposed animals in CA1, CA3, and DG compared to controls, suggesting the microglia have shifted to a more activated state following alcohol treatment. Furthermore, both alcohol-exposed and SI animals had increased levels of pro-inflammatory cytokines IL-1beta, TNF alpha, CD11b, and CCL4; in addition, CCL4 was significantly increased in alcohol exposed animals compared to SI as well. Alcohol-exposed animals also showed increased levels of anti-inflammatory cytokine TGF-beta compared to both SI and SCs. In summary, the number and activation of microglia in the neonatal hippocampus are both affected in a rat model of FASD, along with increased gene expression of pro- and anti-inflammatory cytokines. This study shows that alcohol exposure during development induces a neuroimmune response, potentially contributing to long-term alcohol-related changes to cognition, behavior and immune function. PMID- 26996515 TI - Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature. AB - BACKGROUND: The most feared bleeding complication in fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an intracranial hemorrhage (ICH). However, FNAIT may also lead to other severe bleeding problems. The aim was to analyze this spectrum and evaluate the occurrence of severe hemorrhages other than ICH in fetuses or neonates with FNAIT. STUDY DESIGN AND METHODS: A retrospective chart analysis of cases of FNAIT presenting with severe bleeding complications other than ICH at our institution from 1990 to 2015 was conducted. Additionally, a review of the literature was performed to identify case reports and case series on FNAIT presenting with extracranial hemorrhage. RESULTS: Of 25 fetuses or neonates with severe bleeding due to FNAIT, three had isolated severe internal organ hemorrhage other than ICH, two pulmonary hemorrhages and one gastrointestinal hemorrhage. Two of these three neonates died due to this bleeding. Eighteen cases of extracranial bleeding complications as a first presentation of FNAIT were found in the literature, including ocular, gastrointestinal, spinal cord, pulmonary, renal, subgaleal, and genitourinary hemorrhages. CONCLUSION: Bleeding complications other than ICH may be more extensive, and the presentation of FNAIT may have a greater spectrum than previously described. A high index of suspicion on the possible diagnosis of FNAIT with any bleeding complication in a fetus or neonate may enable adequate diagnostics, adequate treatment, and appropriate follow-up in future pregnancies, as is especially relevant for FNAIT. PMID- 26996514 TI - Magnetic Resonance Imaging Revealed Splenic Targeting of Canine Parvovirus Capsid Protein VP2. AB - Canine parvovirus (CPV) is a highly contagious infectious virus, whose infectious mechanism remains unclear because of acute gastroenteritis and the lack of an efficient tool to visualize the virus in real time during virology research. In this study, we developed an iron oxide nanoparticle supported by graphene quantum dots (GQD), namely, FeGQD. In this composite material, GQD acts as a stabilizer; thus, vacancies are retained on the surface for further physical adsorption of the CPV VP2 protein. The FeGQD@VP2 nanocomposite product showed largely enhanced colloidal stability in comparison with bare FeGQD, as well as negligible toxicity both in vitro and in vivo. The composite displayed high uptake into transferrin receptor (TfR) positive cells, which are distinguishable from FeGQD or TfR negative cells. In addition, the composite developed a significant accumulation in spleen rather than in liver, where bare FeGQD or most iron oxide nanoparticles gather. As these evident targeting abilities of FeGQD@VP2 strongly suggested, the biological activity of CPV VP2 was retained in our study, and its biological functions might correspond to CPV when the rare splenic targeting ability is considered. This approach can be applied to numerous other biomedical studies that require a simple yet efficient approach to track proteins in vivo while retaining biological function and may facilitate virus-related research. PMID- 26996516 TI - Evidence of the phenotypic expression of a lethal recessive allele under inbreeding in a wild population of conservation concern. AB - Deleterious recessive alleles that are masked in outbred populations are predicted to be expressed in small, inbred populations, reducing both individual fitness and population viability. However, there are few definitive examples of phenotypic expression of lethal recessive alleles under inbreeding conditions in wild populations. Studies that demonstrate the action of such alleles, and infer their distribution and dynamics, are required to understand their potential impact on population viability and inform management responses. The Scottish population of red-billed choughs (Pyrrhocorax pyrrhocorax), which currently totals <60 breeding pairs and is of major conservation concern, has recently been affected by lethal blindness in nestlings. We used family data to show that the pattern of occurrence of blindness within and across affected families that produced blind nestlings was exactly 0.25, matching that expected given a single locus autosomal lethal recessive allele. Furthermore, the observed distribution of blind nestlings within affected families did not differ from that expected given Mendelian inheritance of such an allele. Relatedness estimates showed that individuals from affected families were not more closely related to each other than they were to individuals from unaffected families that did not produce blind nestlings. Blind individuals tended to be less heterozygous than non-blind individuals, as expected if blindness was caused by the expression of a recessive allele under inbreeding. However, there was no difference in the variance in heterozygosity estimates, suggesting that some blind individuals were relatively outbred. These results suggest carriers of the blindness allele may be widely distributed across contemporary families rather than restricted to a single family lineage, implying that the allele has persisted across multiple generations. Blindness occurred at low frequency (affecting 1.6% of observed nestlings since 1981). However, affected families had larger initial brood sizes than unaffected families. Such high fecundity of carriers of a lethal recessive allele might reflect overdominance, potentially reducing purging and increasing allele persistence probability. We thereby demonstrate the phenotypic expression of a lethal recessive allele in a wild population of conservation concern, and provide a general framework for inferring allele distribution and persistence and informing management responses. PMID- 26996517 TI - Arsenic-Containing Phosphatidylcholines: A New Group of Arsenolipids Discovered in Herring Caviar. AB - A new group of arsenolipids based on cell-membrane phosphatidylcholines has been discovered in herring caviar (fish roe). A combination of HPLC with elemental and molecular mass spectrometry was used to identify five arsenic-containing phosphatidylcholines; the same technique applied to salmon caviar identified an arsenic-containing phosphatidylethanolamine. The arsenic group in these membrane lipids might impart particular properties to the molecules not displayed by their non-arsenic analogues. Additionally, the new compounds have human health implications according to recent results showing high cytotoxicity for some arsenolipids. PMID- 26996519 TI - Sex-specific incidence rates and risk factors of insulin resistance and beta-cell dysfunction: a decade follow-up in a Middle Eastern population. AB - AIMS: To examine the incidence of and risk factors for insulin resistance and beta-cell dysfunction in a representative Iranian population over a median follow up of 9.2 years. METHODS: In total, 3662 people (1528 men) without known diabetes with a baseline homeostasis model assessment of insulin resistance (HOMA-IR) level < 75th percentile and, when beta-cell dysfunction was the outcome of interest, 3664 people (1530 men) with a homeostasis model assessment of beta-cell function (HOMA-beta) level >= 25th percentile were included in the study (HOMA-IR < 2.20 and HOMA-beta >= 64.3 among men, and HOMA-IR < 2.39 and HOMA-beta >= 81.7 among women). RESULTS: The incidence rates of insulin resistance and beta-cell dysfunction were 56.3 and 33.6/1000 person-years among men and 48.6 and 50.3/1000 person-years among women, respectively. Applying multivariable Cox regression in both sexes, fasting insulin, triglyceride/HDL cholesterol ratio and lower education were positive predictors of insulin resistance, whereas age was a negative predictor. Moreover, fasting plasma glucose, waist-to-height ratio, wrist circumference and lower hip circumference were significantly associated with incident insulin resistance only among women (all P < 0.05). Considering beta-cell dysfunction in both sexes, age and fasting plasma glucose increased the risk, whereas 2-h post-challenge plasma glucose was a positive predictor only among men, and waist-to-height ratio and triglyceride/HDL cholesterol ratio were negative predictors only among women (all P < 0.05). CONCLUSIONS: Modifiable risk factors are related to the incidence of insulin resistance and beta-cell dysfunction, which can be prevented with proper strategies although the difference between men and women should be taken into account. PMID- 26996518 TI - Concise review: programming human pluripotent stem cells into blood. AB - Blood disorders are treated with cell therapies including haematopoietic stem cell (HSC) transplantation as well as platelet and red blood cell transfusions. However the source of cells is entirely dependent on donors, procedures are susceptible to transfusion-transmitted infections and serious complications can arise in recipients due to immunological incompatibility. These problems could be alleviated if it was possible to produce haematopoietic cells in vitro from an autologous and renewable cell source. The production of haematopoietic cells in the laboratory from human induced pluripotent stem cells (iPSCs) may provide a route to realize this goal but it has proven challenging to generate long-term reconstituting HSCs. To date, the optimization of differentiation protocols has mostly relied on the manipulation of extrinsic signals to mimic the in vivo environment. We review studies that have taken an alternative approach to modulate intrinsic signals by enforced expression of transcription factors. Single and combinations of multiple transcription factors have been used in a variety of contexts to enhance the production of haematopoietic cells from human pluripotent stem cells. This programming approach, together with the recent advances in the production and use of synthetic transcription factors, holds great promise for the production of fully functional HSCs in the future. PMID- 26996520 TI - Tuberculosis in Rhinoceros: An Underrecognized Threat? AB - Historical evidence of tuberculosis (TB) affecting primarily captive rhinoceroses dates back almost two centuries. Although the causative Mycobacterium tuberculosis complex (MTC) species has not been determined in many cases, especially for those that occurred before bacterial culture techniques were available, the spectrum of documented reports illustrates the importance of TB as cause of morbidity and mortality in different rhinoceros species across continents. In more recent years, sporadic suspected or confirmed cases of TB caused by Mycobacterium bovis (M. bovis) have been reported in semi-free or free ranging rhinoceroses in South Africa. However, the true risk TB may pose to the health and conservation of rhinoceros populations in the country's large conservation areas where M. bovis is endemic, which is unknown. Underlying the current knowledge gap is the lack of diagnostic tools available to detect infection in living animals. As documented in other wildlife species, TB could establish itself in a rhinoceros population but remain unrecognized for decades with detrimental implications for wildlife conservation at large and should such animals be moved to uninfected areas or facilities. This paper reviews the current state of knowledge regarding TB in rhinoceros including critical gaps that need to be addressed to effectively assess the threat that this disease may present to rhinoceros. PMID- 26996521 TI - Cryogenic processes and fire activity in a high Atlantic mountain area in NW Iberia (Picos de Europa) during the Mid-Late Holocene. AB - Mid-Late Holocene environmental changes in the Cantabrian Mountains are a consequence of both climate variability and human activity. A 182cm-long sedimentary sequence was collected from Belbin depression, Western Massif of Picos de Europa (Cantabrian Mountains, NW Spain), in order to reconstruct Holocene environmental dynamics and the factors triggering landscape changes in the area. Using multi-proxy analysis of the uppermost 60cm of the sediments (texture, organic matter content, quartz grains microstructures, charcoal deposition) together with three 14C AMS dates, a sequence of alternating warmer and colder phases has been inferred for the last ca. 6.7kycalBP. Warm stages are defined by low to moderate chemical weathering of the quartz grain particles with relative increases of the C/N ratio, while colder phases show a moderate to intense physical weathering of the quartz grains and lower C/N ratios. Warmer temperatures were recorded in Belbin area between: 6.7-5, 3.7-3, 2.6-1.1, 0.87 0.51 and since 0.01kycalBP. A colder regime occurred between 5-3.7, 3-2.6, 1.1 0.87 and 0.51 to 0.01kycalBP. The increasing organic matter content during the Late Holocene may be associated with increasing temperatures. The charcoal particles do not show a higher or lower concentration during prevailing colder or warmer conditions, and therefore may be linked to human-induced fire management of the landscape. The most intense period with fire activity occurred between 3.5 and 3kycalBP during the Bronze Age. PMID- 26996523 TI - Productivity in a dominant herbaceous species is largely unrelated to soil macronutrient stocks. AB - To predict ecosystem responses to anthropogenic change it is important to understand how and where plant productivity is limited by macronutrient availability. Nitrogen (N) is required in large quantities for plant growth, and is readily lost through leaching or gas fluxes, but reactive nitrogen can be obtained through dinitrogen fixation, and phosphorus (P) is often considered a more fundamental long-term constraint to growth and carbon sequestration in terrestrial ecosystems. Phosphorus limitation may be becoming more prevalent due to widespread pollution by atmospheric N. Assessments of the effects of macronutrient availability on productivity in natural ecosystems are however scarce. We measured standing biomass of bracken Pteridium aquilinum as a proxy for productivity across sites with similar climate but varied geology. Total above-ground biomass varied from 404 to 1947gm-2, yet despite 12-fold to 281-fold variation in soil macronutrient stocks these were remarkably poor at explaining variation in productivity. Soil total nitrogen, organic phosphorus, calcium, magnesium and zinc had no relationship with productivity, whether expressed as concentrations, stocks or element/C ratios, and nor did foliar N/P. Soil potassium (K) and molybdenum stocks both showed weak relationships with productivity. The stock of K in bracken biomass was considerably greater as a proportion of soil stock than for other nutrient elements, suggesting that this nutrient element can be important in determining productivity. Moisture availability, as indicated by environmental trait scores for plant species present, explained considerably more of the variation in productivity than did K stock, with less production in wetter sites. Soil N/C ratio and organic P stock were relatively unimportant in determining productivity across these bracken sites. It is possible that more-direct measures of N and P availability would explain variation in productivity, but the study shows the importance of considering other essential elements and other environmental factors when predicting productivity. PMID- 26996524 TI - Comparative study between chemostat and batch reactors to quantify membrane permeability changes on bacteria exposed to silver nanoparticles. AB - Continuous and batch reactors were used to assess the effect of the exposure of casein-coated silver nanoparticles (AgNPs) on Escherichia coli (E. coli). Additionally, E. coli membrane extracts, membrane permeability and Langmuir film balance assays were used to determine integrity and changes in lipid composition in response to AgNPs exposure. Results showed that batch conditions were not appropriate for the tests due to the production of exopolymeric substances (EPS) during the growth phase. After 5h of contact between AgNPs and the used growth media containing EPS, the nanoparticles increased in size from 86nm to 282nm reducing the stability and thus limiting cell-nanoparticle interactions. AgNPs reduced E. coli growth by 20% at 1mg/L, in terms of Optical Density 670 (OD670), while no effect was detected at 15mg/L. At 50mg/L of AgNPs was not possible to perform the test due to aggregation and sedimentation of the nanoparticles. Membrane extract assays showed that at 1mg/L AgNPs had a greater change in area ( 4.4cm(2)) on bacteria compared to 15mg/L (-4.0cm(2)). This area increment suggested that membrane disruption caused by AgNPs had a stabilizing/rigidifying effect where the cells responded by shifting their lipid composition to more unsaturated lipids to counteract membrane rigidification. In chemostats, the constant inflow of fresh media and aeration resulted in less AgNPs aggregation, thus increased the AgNPs-bacteria interactions, in comparison to batch conditions. AgNPs at 1mg/L, 15mg/L, and 50mg/L inhibited the growth (OD670 reduction) by 0%, 11% and 16.3%, respectively. Membrane extracts exposed to 1mg/L, 15mg/L, and 50mg/L of AgNPs required greater changes in area by -0.5cm(2), 2.7cm(2) and 3.6cm(2), respectively, indicating that the bacterial membranes were disrupted and bacteria responded by synthesizing lipids that stabilize or strengthen membranes. This study showed that the chemostat is more appropriate for the testing of nanotoxicological effects when testing bacteria at growing conditions. PMID- 26996525 TI - Multiscale Graphene Topographies Programmed by Sequential Mechanical Deformation. AB - Multigenerational graphene oxide architectures can be programmed by specific sequences of mechanical deformations. Each new deformation results in a progressively larger set of features decorated by smaller preexisting patterns, indicating a structural "memory." It is shown that these multiscale architectures are superhydrophobic and display excellent functionality as electrochemical electrodes. PMID- 26996522 TI - Mercury risk to avian piscivores across western United States and Canada. AB - The widespread distribution of mercury (Hg) threatens wildlife health, particularly piscivorous birds. Western North America is a diverse region that provides critical habitat to many piscivorous bird species, and also has a well documented history of mercury contamination from legacy mining and atmospheric deposition. The diversity of landscapes in the west limits the distribution of avian piscivore species, complicating broad comparisons across the region. Mercury risk to avian piscivores was evaluated across the western United States and Canada using a suite of avian piscivore species representing a variety of foraging strategies that together occur broadly across the region. Prey fish Hg concentrations were size-adjusted to the preferred size class of the diet for each avian piscivore (Bald Eagle=36cm, Osprey=30cm, Common and Yellow-billed Loon=15cm, Western and Clark's Grebe=6cm, and Belted Kingfisher=5cm) across each species breeding range. Using a combination of field and lab-based studies on Hg effect in a variety of species, wet weight blood estimates were grouped into five relative risk categories including: background (<0.5MUg/g), low (0.5-1MUg/g), moderate (1-2MUg/g), high (2-3MUg/g), and extra high (>3MUg/g). These risk categories were used to estimate potential mercury risk to avian piscivores across the west at a 1degree-by-1degree grid cell resolution. Avian piscivores foraging on larger-sized fish generally were at a higher relative risk to Hg. Habitats with a relatively high risk included wetland complexes (e.g., prairie pothole in Saskatchewan), river deltas (e.g., San Francisco Bay, Puget Sound, Columbia River), and arid lands (Great Basin and central Arizona). These results indicate that more intensive avian piscivore sampling is needed across Western North America to generate a more robust assessment of exposure risk. PMID- 26996526 TI - Evaluation of the Right Ventricular Function in Prediabetes: A 2-D Speckle Tracking Echocardiographic Study. AB - Pre-diabetes is a common condition associated with cardiovascular changes. The aim of our study was to evaluate the right ventricular (RV) function as assessed by 2-D speckle tracking echocardiography in pre-diabetic patients. This study recruited 94 patients (33 normal patients, 31 pre-diabetic patients and 30 diabetic patients). The absolute amount of the global peak systolic strain, the systolic strain rate and the early diastolic strain rate of the RV free wall (RVFW) was higher in the control group than in the pre-diabetic and diabetic groups. These indices were not different between the pre-diabetic and diabetic groups. The global late diastolic strain rate of RVFW was the same between the three groups. Also, pre-diabetes and diabetes were the independent predictors of the RVFW global peak systolic strain, systolic strain rate and diastolic strain rate. Our study demonstrated that the RV systolic and diastolic functions were impaired in the pre-diabetic and diabetic patients without obstructive coronary artery disease. Also, pre-diabetes and diabetes were independent predictors of systolic and diastolic functions of the RV. PMID- 26996527 TI - Photocatalytic Reduction of Carbon Dioxide to CO and HCO2H Using fac Mn(CN)(bpy)(CO)3. AB - Studies are reported regarding the use of Mn(CN)(bpy)(CO)3 (1) as a catalyst for CO2 reduction employing [Ru(dmb)3](2+) as a photosensitizer in mixtures of dry N,N-dimethylformamide-triethanolamine (N,N-DMF-TEOA) or acetonitrile-TEOA (MeCN TEOA) with 1-benzyl-1,4-dihydronicotinamide as a sacrificial reductant. Irradiation with 470 nm light for up to 15 h yields both CO and HCO2H with maximum turnover numbers (TONs) as high as 21 and 127, respectively, with product preference dependent on the solvent. Further data suggests that upon single electron reduction this catalyst avoids the formation of a Mn-Mn dimer and instead undergoes a disproportionation reaction, which requires 2 equiv of [Mn(CN)(bpy)(CO)3](*-) to generate 1 equiv each of the active catalyst [Mn(bpy)(CO)3](-) and the starting compound 1. Additional characterization by cyclic voltammetry (CV) and infrared spectroelectrochemistry (IR-SEC) indicates that the stability of the singly reduced [Mn(CN)(bpy)(CO)3](*-) differs slightly in the N,N-DMF-TEOA solvent system compared to the MeCN-TEOA system. This contributes to the observed selectivities for HCO2H vs CO production. PMID- 26996529 TI - MicroRNA 152 regulates hepatic glycogenesis by targeting PTEN. AB - Hepatic insulin resistance, defined as a diminished ability of hepatocytes to respond to the action of insulin, plays an important role in the development of type 2 diabetes and metabolic syndrome. Aberrant expression of mmu-miR-152-3p (miR-152) is related to the pathogenesis of tumors such as hepatitis B virus related hepatocellular carcinoma. However, the role of miR-152 in hepatic insulin resistance remains unknown. In the present study, we identified the potential role of miR-152 in regulating hepatic glycogenesis. The expression of miR-152 and the level of glycogen were significantly downregulated in the liver of db/db mice and mice fed a high fat diet. In vivo and in vitro results suggest that inhibition of miR-152 expression induced impaired glycogenesis in hepatocytes. Interestingly, miR-152 expression, glycogen synthesis and protein kinase B/glycogen synthase kinase (AKT/GSK) pathway activation were significantly decreased in the liver of mice injected with 16 MUg.mL(-1) interleukin 6 (IL-6) by pumps for 7 days and in NCTC 1469 cells treated with 10 ng.mL(-1) IL-6 for 24 h. Moreover, hepatic overexpression of miR-152 rescued IL-6-induced impaired glycogenesis. Finally, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-152 to mediate hepatic glycogen synthesis. Our findings provide mechanistic insight into the effects of miR-152 on the regulation of the AKT/GSK pathway and the synthesis of glycogen in hepatocytes. Downregulated miR 152 induced impaired hepatic glycogenesis by targeting PTEN. PTEN participated in miR-152-mediated glycogenesis in hepatocytes via regulation of the AKT/GSK pathway. PMID- 26996530 TI - Amelioration of Ischemic Brain Injury in Rats With Human Umbilical Cord Blood Stem Cells: Mechanisms of Action. AB - Despite the high prevalence and devastating outcome, there remain a few options for treatment of ischemic stroke. Currently available treatments are limited by a short time window for treatment and marginal efficacy when used. We have tested a human umbilical cord blood-derived stem cell line that has been shown to result in a significant reduction in stroke infarct volume as well as improved functional recovery following stroke in the rat. In the present study we address the mechanism of action and compared the therapeutic efficacy of high- versus low passage nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs). Using the middle cerebral arterial occlusion (MCAo) model of stroke in Sprague-Dawley rats, we administered nh-UCBSC by intravenous (IV) injection 2 days following stroke induction. These human cells were injected into rats without any immune suppression, and no adverse reactions were detected. Both behavioral and histological analyses have shown that the administration of these cells reduces the infarct volume by 50% as well as improves the functional outcome of these rats following stroke for both high- and low-passaged nh-UCBSCs. Flow cytometry analysis of immune cells present in the brains of normal rats, rats with ischemic brain injury, and ischemic animals with nh-UCBSC treatment confirmed infiltration of macrophages and T cells consequent to ischemia and reduction to normal levels with nh-UCBSC treatment. Flow cytometry also revealed a restoration of normal levels of microglia in the brain following treatment. These data suggest that nh UCBSCs may act by inhibiting immune cell migration into the brain from the periphery and possibly by inhibition of immune cell activation within the brain. nh-UCBSCs exhibit great potential for treatment of stroke, including the fact that they are associated with an increased therapeutic time window, no known ill effects, and that they can be expanded to high numbers for, and stored for, treatment. PMID- 26996528 TI - Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration. AB - Human pluripotent stem cells (hPSCs), including both embryonic and induced pluripotent stem cells, possess the unique ability to readily differentiate into any cell type of the body, including cells of the retina. Although previous studies have demonstrated the ability to differentiate hPSCs to a retinal lineage, the ability to derive retinal ganglion cells (RGCs) from hPSCs has been complicated by the lack of specific markers with which to identify these cells from a pluripotent source. In the current study, the definitive identification of hPSC-derived RGCs was accomplished by their directed, stepwise differentiation through an enriched retinal progenitor intermediary, with resultant RGCs expressing a full complement of associated features and proper functional characteristics. These results served as the basis for the establishment of induced pluripotent stem cells (iPSCs) from a patient with a genetically inherited form of glaucoma, which results in damage and loss of RGCs. Patient derived RGCs specifically exhibited a dramatic increase in apoptosis, similar to the targeted loss of RGCs in glaucoma, which was significantly rescued by the addition of candidate neuroprotective factors. Thus, the current study serves to establish a method by which to definitively acquire and identify RGCs from hPSCs and demonstrates the ability of hPSCs to serve as an effective in vitro model of disease progression. Moreover, iPSC-derived RGCs can be utilized for future drug screening approaches to identify targets for the treatment of glaucoma and other optic neuropathies. Stem Cells 2016;34:1553-1562. PMID- 26996532 TI - Trauma research in the Baltic countries: from political oppression to recovery. AB - The aim of this paper is to provide an overview of traumatic stress studies from the three Baltic countries-Lithuania, Latvia, and Estonia-and reveal how specific social context contributes to the topics relevant in traumatic stress field in the region. Traumatic stress studies in the Baltic countries are closely related to the complicated history of the region. It was only since the restoration of independence of the Baltic States in the 1990s when traumatic stress studies could emerge. The start of the psychotraumatology in the Baltic States was inspired by the interest of the psychological effects of political violence. Four major topics in traumatic stress literature from the Baltic countries were identified in this article: political violence studies, epidemiology of trauma and posttraumatic stress disorder (PTSD), disaster studies, and developmental aspects of trauma. Traumatic events prevalence was reported between 70 and 75%, and PTSD prevalence range 2-7% in the Baltic countries. The interest in psychotraumatology in the Baltic countries is rising. PMID- 26996531 TI - Social attachments and traumatic stress. AB - The extent to which we engage with our social world has been central to our survival as a species and, accordingly, is relevant to how we cope with trauma and adversity. This review summarises current knowledge about the importance of social connections from an evolutionary perspective, as well as integrating this with a discussion of prevailing attachment theories. Experimental research supporting the potential benefit of attachments for managing adversity are presented, along with a review of how these benefits are moderated by individual differences in attachment style. The potential impact of trauma on attachment systems, and the manner in which this can compound trauma stress is discussed. Finally, a broader overview of social network analysis is introduced and it is proposed that a more sociocentric framework of trauma response would promote a fuller understanding of how social processes moderate trauma response. PMID- 26996533 TI - Broadening perspectives on trauma and recovery: a socio-interpersonal view of PTSD. AB - Posttraumatic stress disorder (PTSD) is one of the very few mental disorders that requires by definition an environmental context-a traumatic event or events-as a precondition for diagnosis. Both trauma sequelae and recovery always occur in the context of social-interpersonal contexts, for example, in interaction with a partner, family, the community, and the society. The present paper elaborates and extends the social-interpersonal framework model of PTSD. This was developed to complement other intrapersonally focused models of PTSD, which emphasize alterations in an individual's memory, cognitions, or neurobiology. Four primary reasons for broadening the perspective from the individual to the interpersonal societal contexts are discussed. The three layers of the model (social affects, close relationships, and culture and society) are outlined. We further discuss additional insights and benefits of the social-interpersonal perspective for the growing field of research regarding resilience after traumatic experiences. The paper closes with an outlook on therapy approaches and interventions considering this broader social-interpersonal perspective on PTSD. PMID- 26996534 TI - Trauma treatment across Europe: where do we stand now from a perspective of seven countries. AB - There is a lack of knowledge about the state of affairs of the trauma treatments in Europe. To start to fill in this gap, key persons from seven European countries-Georgia, Germany, Lithuania, the Netherlands, Poland, Switzerland, and Turkey-accepted the invitation to give their expert opinion on the state of affairs in their country at an invited panel discussion at the XIV 2015 ESTSS Conference in Vilnius, Lithuania. Brief reports from the seven countries reveal significant diversities among different European countries in terms of awareness of health problems related to trauma, the availability of trauma treatments, and treatment approaches. Political and economic differences across the European countries contribute to the diversities in the developments of trauma treatments. European national psychotrauma societies are active in establishing training curricula and dissemination of trauma-focused treatments. Despite the growing acknowledgment of trauma and dissemination of trauma-focused treatments, there is a lack of Europe-wide policies to ensure availability of trauma treatment in Europe for trauma survivors. The need for more detailed analysis of trauma treatment in all European countries and development of European-level trauma informed health care policies is outlined. PMID- 26996535 TI - Investigating biological traces of traumatic stress in changing societies: challenges and directions from the ESTSS Task Force on Neurobiology. AB - Traumatic stress can have severe consequences for both mental and physical health. Furthermore, both psychological and biological traces of trauma increase as a function of accumulating traumatic experiences. Neurobiological research may aid in limiting the impact of traumatic stress, by leading to advances in preventive and treatment interventions. To promote the possibility for clinical implementation of novel research findings, this brief review describes timely conceptual and methodological challenges and directions in neurobiological trauma research on behalf of the Task Force "Neurobiology of Traumatic Stress" of the European Society for Traumatic Stress Studies (ESTSS). The most important conceptual challenges are the heterogeneity of disorders and existence of subtypes across diagnostic categories: differential latent profiles and trajectories regarding symptom expression and neural correlates are being unraveled; however, similar latent classes' approaches for treatment response and neurobiological data remain scarce thus far. The key to improving the efficacy of currently available preventive interventions and treatments for trauma-related disorders lies in a better understanding and characterization of individual differences in response to trauma and interventions. This could lead to personalized treatment strategies for trauma-related disorders, based on objective information indicating whether individuals are expected to benefit from them. The most important methodological challenge identified here is the need for large consortia and meta-analyses or, rather, mega-analyses on existent data as a first step. In addition, large multicenter studies, combining novel methods for repeated sampling with more advanced statistical modeling techniques, such as machine learning, should aim to translate identified disease mechanisms into molecular blood-based biomarker combinations to predict disorder vulnerability and treatment responses. PMID- 26996536 TI - Prevention and public health approaches to trauma and traumatic stress: a rationale and a call to action. AB - BACKGROUND: The field of trauma and traumatic stress is dominated by studies on treatments for those who experience adversity from traumatic experiences. While this is important, we should not neglect the opportunity to consider trauma in a public health perspective. Such a perspective will help to develop prevention approaches as well as extend the reach of early interventions and treatments. The purpose of this paper is to provide an introduction to a public health approach to trauma and traumatic stress and identify key opportunities for trauma professionals and our professional societies (such as the International Society for Traumatic Stress Studies [ISTSS] and the European Society for Traumatic Stress Studies [ESTSS]) to increase our societal impact by adopting such an approach. METHOD: This paper reviews and summarizes key findings related to the public health impact of trauma. The special case of children is explored, and a case example of the Norwegian terrorist attacks in 2011 illustrates the potential for improving our response to community level traumatic events. We also discuss how professional organizations such as ESTSS and ISTSS, as well as individual trauma professionals, can and should play an important role in promoting a public health approach. RESULTS: Trauma is pervasive throughout the world and has negative impacts at the personal, family, community, and societal levels. A public health perspective may help to develop prevention approaches at all of these levels, as well as extend the reach of early interventions and treatments. CONCLUSIONS: Professional organizations such as ESTSS and ISTSS can and should play an important role in promoting a public health approach. They should promote the inclusion of trauma in the global public health agenda and include public health in their activities. PMID- 26996537 TI - Production of a single cyclic type of fructooligosaccharide structure by inulin degrading Paenibacillus sp. LX16 newly isolated from Jerusalem artichoke root. AB - A novel inulin-degrading bacterium was isolated from a soil sample collected on Jerusalem artichoke roots. It is a Gram-positive, aerobic, motile and central endospore-forming straight rod, and exhibits phenotypic properties being consistent with its classification in the genus Paenibacillus. The predominant cellular fatty acids were anteiso-C15:0, C16:0 and anteiso-C17:0. This strain represents a novel species of the genus Paenibacillus on the basis of phenotypic data together with phylogenetic analysis, and it is here designated as LX16 and deposited in China centre for type collection, China (= CCTCC 2015256). Strain LX16 could produce a cyclofructooligosaccharide fructanotransferase catalysing the formation of one type of fructooligosaccharide (FOS) from inulin. The FOS was identified as a cyclofructooligosaccharide with a degree of polymerization of 6. Such homology in inulin degradation products may be beneficial for the functional FOS production. PMID- 26996538 TI - Optical fiber sensor based on surface plasmon resonance for rapid detection of avian influenza virus subtype H6: Initial studies. AB - A side-polished fiber optic surface plasmon resonance (SPR) sensor was fabricated to expose the core surface and then deposited with a 40 nm thin gold film for the near surface sensing of effective refractive index changes with surface concentration or thickness of captured avian influenza virus subtype H6. The detection surface of the SPR optical fiber sensor was prepared through the plasma modification method for binding a self-assembled monolayer of isopropanol chemically on the gold surface of the optical fiber. Subsequently, N-(3 dimethylaminopropyl)-N'-ethylcarbodiimide/N-hydroxysuccinimide was activated to enable EB2-B3 monoclonal antibodies to capture A/chicken/Taiwan/2838V/00 (H6N1) through a flow injection system. The detection limit of the fabricated optical fiber sensor for A/chicken/Taiwan/2838V/00 was 5.14 * 10(5) EID50/0.1 mL, and the response time was 10 min on average. Moreover, the fiber optic sensor has the advantages of a compact size and low cost, thus rendering it suitable for online and remote sensing. The results indicated that the optical fiber sensor can be used for epidemiological surveillance and diagnosing of avian influenza subtype H6 rapidly. PMID- 26996539 TI - Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure. AB - The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP-coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO3 . Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg-1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO3 up to 1 mg kg-1 body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO3 treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO3 treated rats. However, the comparisons between AgNPs and AgNO3 treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609-618, 2017. PMID- 26996540 TI - The number of Purkinje neurons and their topology in the cerebellar vermis of normal and reln haplodeficient mouse. AB - The Reeler heterozygous mice (reln(+/-)) are haplodeficient in the gene (reln) encoding for the reelin glycoprotein (RELN) and display reductions in brain/peripheral RELN similar to autistic or schizophrenic patients. Cytoarchitectonic alterations of the reln(+/-) brain may be subtle, and are difficult to demonstrate by current histological approaches. We analyzed the number and topological organization of the Purkinje neurons (PNs) in five vermal lobules - central (II-III), culmen (IV-V), tuber (VIIb), uvula (IX), and nodulus (X) - that process different types of afferent functional inputs in reln(+/+) and reln(+/-) adult mice (P60) of both sexes (n=24). Animals were crossed with L7GFP mice so that the GFP-tagged PNs could be directly identified in cryosections. Digital images from these sections were processed with different open source software for quantitative topological and statistical analyses. Diversity indices calculated were: maximum caliper, density, area of soma, dispersion along the XZ axis, and dispersion along the YZ axis. We demonstrate: i. reduction in density of PNs in reln(+/-) males (14.37%) and reln(+/-) females (17.73%) compared to reln(+/+) males; ii. that reln(+/-) males have larger PNs than other genotypes, and females (irrespective of the reln genetic background) have smaller PNs than reln(+/+) males; iii. PNs are more chaotically arranged along the YZ axis in reln(+/-) males than in reln(+/+) males and, except in central lobulus, reln(+/-) females. Therefore, image processing and statistics reveal previously unforeseen gender and genotype-related structural differences in cerebellum that may be clues for the definition of novel biomarkers in human psychiatric disorders. PMID- 26996541 TI - Best teaching practices in anatomy education: A critical review. AB - In this report we review the range of teaching resources and strategies used in anatomy education with the aim of coming up with suggestions about the best teaching practices in this area. There is much debate about suitable methods of delivering anatomical knowledge. Competent clinicians, particularly surgeons, need a deep understanding of anatomy for safe clinical procedures. However, because students have had very limited exposure to anatomy during clinical training, there is a concern that medical students are ill-prepared in anatomy when entering clerkships and residency programs. Therefore, developing effective modalities for teaching anatomy is essential to safe medical practice. Cadaver based instruction has survived as the main instructional tool for hundreds of years, however, there are differing views on whether full cadaver dissection is still appropriate for a modern undergraduate training. The limitations on curricular time, trained anatomy faculty and resources for gross anatomy courses in integrated or/and system-based curricula, have led many medical schools to abandon costly and time-consuming dissection-based instruction in favour of alternative methods of instruction including prosection, medical imaging, living anatomy and multimedia resources. To date, no single teaching tool has been found to meet curriculum requirements. The best way to teach modern anatomy is by combining multiple pedagogical resources to complement one another, students appear to learn more effectively when multimodal and system-based approaches are integrated. Our review suggests that certain professions would have more benefit from certain educational methods or strategies than others. Full body dissection would be best reserved for medical students, especially those with surgical career intentions, while teaching based on prosections and plastination is more suitable for dental, pharmacy and allied health science students. There is a need to direct future research towards evaluation of the suitability of the new teaching methodologies in new curricula and student perceptions of integrated and multimodal teaching paradigms, and the ability of these to satisfy learning outcomes. PMID- 26996542 TI - Performance and safety of an integrated bihormonal artificial pancreas for fully automated glucose control at home. AB - AIMS: To assess the performance and safety of an integrated bihormonal artificial pancreas system consisting of one wearable device and two wireless glucose sensor transmitters during short-term daily use at home. METHODS: Adult patients with type 1 diabetes using an insulin pump were invited to enrol in this randomized crossover study. Treatment with the artificial pancreas started with a day and night in the clinical research centre, followed by 3 days at home. The control period consisted of 4 days of insulin pump therapy at home with blinded continuous glucose monitoring for data collection. Days 2-4 were predefined as the analysis period, with median glucose as the primary outcome. RESULTS: A total of 10 patients completed the study. The median [interquartile range (IQR)] glucose level was similar for the two treatments [7.3 (7.0-7.6) mmol/l for the artificial pancreas vs. 7.7 (7.0-9.0) mmol/l for the control; p = 0.123]. The median (IQR) percentage of time spent in euglycaemia (3.9-10 mmol/l) was longer during use of the artificial pancreas [84.7 (82.2-87.8)% for the artificial pancreas vs. 68.5 (57.9-83.6)% for the control; p = 0.007]. Time in hypoglycaemia was 1.3 (0.2-3.2)% for the artificial pancreas and 2.4 (0.4-10.3)% for the control treatment (p = 0.139). Separate analysis of daytime and night-time showed that the improvements were mainly achieved during the night. CONCLUSIONS: The results of this pilot study suggest that our integrated artificial pancreas provides better glucose control than insulin pump therapy in patients with type 1 diabetes at home and that the treatment is safe. PMID- 26996543 TI - Mangiferin induces apoptosis in multiple myeloma cell lines by suppressing the activation of nuclear factor kappa B-inducing kinase. AB - Mangiferin is a naturally occurring glucosyl xanthone, which induces apoptosis in various cancer cells. However, the molecular mechanism underlying mangiferin induced apoptosis has not been clarified thus far. Therefore, we examined the molecular mechanism underlying mangiferin-induced apoptosis in multiple myeloma (MM) cell lines. We found that mangiferin decreased the viability of MM cell lines in a concentration-dependent manner. We also observed an increased number of apoptotic cells, caspase-3 activation, and a decrease in the mitochondrial membrane potential. In addition, mangiferin inhibited the nuclear translocation of nuclear factor kappa B (NF-kappaB) and expression of phosphorylated inhibitor kappa B (IkappaB) and increased the expression of IkappaB protein, whereas no changes were observed in the phosphorylation levels of extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase 1/2 (JNK1/2), and mammalian target of rapamycin (mTOR). The molecular mechanism responsible for mangiferin-induced inhibition of nuclear translocation of NF-kappaB was a decrease in the expression of phosphorylated NF-kappaB-inducing kinase (NIK). Moreover, mangiferin decreased the expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, and Bcl-xL proteins. Knockdown of NIK expression showed results similar to those observed with mangiferin treatment. Our results suggest that mangiferin induces apoptosis through the inhibition of nuclear translocation of NF-kappaB by suppressing NIK activation in MM cell lines. Our results provide a new insight into the molecular mechanism of mangiferin-induced apoptosis. Importantly, since the number of reported NIK inhibitors is limited, mangiferin, which targets NIK, may be a potential anticancer agent for the treatment of MM. PMID- 26996544 TI - Synthetic catecholamine triggers beta1-adrenergic receptor activation and stimulates cardiotoxicity via oxidative stress mediated apoptotic cell death in rats: Abrogating action of thymol. AB - Nowadays, there are considerable interests in the studies which are more connected with the impact of natural antioxidants against the free radical mediated damage in biological systems. Cardiotoxicity is one of the lethal manifestations of cardiovascular diseases (CVDs) which have been associated with the incidence of apoptotic cell death due to oxidative stress. We evaluated the impact of thymol, a dietary monoterpene phenol on isoproterenol (ISO), a synthetic catecholamine and a beta1-adrenergic receptor agonist in rats. Thymol (7.5 mg/kg body weight) was pre and co-treated into male albino Wistar rats daily for a period of 7 days. Induction of cardiotoxicity was done by the subcutaneous administration of ISO (100 mg/kg body weight) into rats on 6th and 7th day. Cardiotoxicity in rats was confirmed by the increased levels/activity of serum troponin-T and creatine kinase in the serum alongwith decreased activity of creatine kinase in the heart. ISO induced cardiotoxic rats also showed a significant increase in the concentrations of lipid peroxidation products and a significant decrease in the activities/levels of antioxidants in the myocardium whereas Reverse Transcription Polymerase Chain Reaction study revealed an increased expression of caspase-8, caspase-9 and Fas genes along with a decreased expression of Bcl-xL gene in the myocardium. Thymol pre and co-treated ISO induced cardiotoxic rats showed considerable protective effects on all the biochemical parameters studied. Histopathological and in vitro findings are found in line with our biochemical findings. Thus, the present study revealed that thymol counters ISO induced cardiotoxicity by inhibiting oxidative stress and apoptotic cell death in rats by virtue of its potent antioxidant property. PMID- 26996546 TI - Comparison of performances of femtosecond laser and microkeratome for thin-flap laser in situ keratomileusis. AB - OBJECTIVE: To compare the clinical outcomes of femtosecond laser (FS) and microkeratome (MK) for thin-flap in situ keratomileusis (LASIK). MATERIALS AND METHODS: Data from patients with moderate to high myopia (spherical equivalent, > 4 diopters [D]) who underwent thin-flap LASIK using FS (199 eyes/110 patients) and MK (157 eyes/86 patients) were analyzed in this retrospective study. Preoperative and postoperative data were recorded from day 1 and months 1 and 3, postoperatively. Visual and refractive outcomes were compared for efficacy, safety, predictability, stability, and the efficacy and safety indices. RESULTS: Three months postoperatively, more eyes in the FS group had an uncorrected distance visual acuity (UCVA) of 20/40 or better compared to MK group (relative risk [RR] 1.01, 95% confidence interval [CI], 0.97-1.05, P = 0.58); significantly more eyes in FS group had an UCVA of 20/20 or better (RR, 1.26, 95%CI, 1.08-1.48, P = 0.003). Intraoperative bleeding occurred in 5% and 36.7%, respectively, of FS and MK groups. There were no significant differences in the refractive predictability within spherical equivalents of 0.5 D (FS, 72%; MK, 63%) and 1.0 D (FS, 90%; MK, 86%). Both groups showed good stability 3 months, postoperatively. The efficacy index in FS group was 113.4%; that in MK group was 102.5% at 3 months postoperatively (P < 0.05). The safety indices for FS and MK groups at 3 months postoperatively were 116.4% and 108.2%, respectively (P < 0.05). CONCLUSIONS: Both methods of thin-flap created LASIK were effective, safe, predicable, and stable. FS group had significant improvements in efficacy and safety, confirmed by the efficacy and safety indices, compared to MK group. Lasers Surg. Med. 48:596-601, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26996545 TI - Lactobacillus reuteri Strains Convert Starch and Maltodextrins into Homoexopolysaccharides Using an Extracellular and Cell-Associated 4,6-alpha Glucanotransferase. AB - Exopolysaccharides (EPS) of lactic acid bacteria (LAB) are of interest for food applications. LAB are well-known to produce alpha-glucan from sucrose by extracellular glucansucrases. Various Lactobacillus reuteri strains also possess 4,6-alpha-glucanotransferase (4,6-alpha-GTase) enzymes. Purified 4,6-alpha-GTases (e.g., GtfB) were shown to act on starches (hydrolysates), cleaving alpha1->4 linkages and synthesizing alpha1->6 linkages, yielding isomalto /maltopolysaccharides (IMMP). Here we report that also L. reuteri cells with these extracellular, cell-associated 4,6-alpha-GTases synthesize EPS (alpha glucan) from starches (hydrolysates). NMR, SEC, and enzymatic hydrolysis of EPS synthesized by L. reuteri 121 cells showed that these have similar linkage specificities but generally are much bigger in size than IMMP produced by the GtfB enzyme. Various IMMP-like EPS are efficiently used as growth substrates by probiotic Bifidobacterium strains that possess amylopullulanase activity. IMMP like EPS thus have potential prebiotic activity and may contribute to the application of probiotic L. reuteri strains grown on maltodextrins or starches as synbiotics. PMID- 26996547 TI - EFP Delphi study on the trends in Periodontology and Periodontics in Europe for the year 2025. AB - AIM: The aim was to assess the potential trends in Periodontology and Periodontics in Europe that might be anticipated by the year 2025, using the Delphi method. MATERIAL AND METHODS: The expert opinion of 120 experts was sought through the use of an open-ended questionnaire, developed by an advisory group, containing 40 questions concerning the various trends in periodontology. RESULTS: The experts (113 responders) expect a stabilization of the prevalence of periodontitis, both for the chronic as well as the aggressive cases, but an increase in implant-related diseases up to the year 2025. Concurrently, the importance of implants is seen to be increasing. They foresee an increased demand for postgraduate periodontology and implantology training. This is mirrored in an increase in publications for implant dentistry and increase in demand and need for training. Concerning the patients, better-informed individuals seeking more routine check-ups are expected. CONCLUSION: A continued need for specialized periodontists, but also well trained dental practitioners is foreseen for next decade in Europe. Apart from periodontology they will be increasingly exposed to and trained in implant dentistry. PMID- 26996548 TI - Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions. AB - Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 * 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol. PMID- 26996549 TI - A Great Teacher of Neurosurgery in Korea: Hun Jae Lee (1921-1983). PMID- 26996550 TI - Update on Early Nutrition and Food Allergy in Children. AB - With growing evidence of an increase in the prevalence, food allergy has been emerged as a new public health problem. As treatment and management of food allergy remain challenging, more attention has been paid to the importance of prevention of food allergy. Although the exact mechanism of recent epidemic is not fully understood, it is suggested that nutritional exposure in early life may play an important role in food allergy development. The underlying hypothesis is that nutritional status or food exposure in the critical period of fetal development can affect the programming of immune system and modify the risk of immunologic reactions to foods in postnatal life. We review accumulating epidemiological studies to examine an association between nutritional exposure during pregnancy or early infancy and food allergy development in children. We also discuss recent advances in the studies of the genetic and epigenetic regulation of food allergy and evaluate the role of early nutrition in food allergy development to provide a new perspective on the prevention of food allergy. PMID- 26996551 TI - Apolipoproteins as Differentiating and Predictive Markers for Assessing Clinical Outcomes in Patients with Small Cell Lung Cancer. AB - PURPOSE: The present study aimed to investigate the value of apolipoproteins, including ApoA-1, ApoC-III, and ApoE, in patients with small cell lung cancer (SCLC) as potential biomarkers for diagnosis, prognosis, and cancer progression. MATERIALS AND METHODS: Lung samples were collected from 89 patients with SCLC. Nineteen lung samples from non-small cell lung cancer (NSCLC) patients and 12 normal lung tissues were used as controls. Expression profiles of ApoA-1, ApoC III, and ApoE in different samples were examined using immunohistochemical methods, and the expression levels were correlated with cancer types, treatment, and outcomes using chi-square and Mann-Whitney tests. RESULTS: Expression of ApoA 1 and ApoC-III in SCLC was significantly different, compared with that in NSCLC and normal lung tissues, and was correlated with recurrence of SCLC. Patients undergoing neoadjuvant chemotherapy before surgery showed significantly reduced expression of ApoA-1 and increased expression of ApoC-III and ApoE. Nevertheless, the expression levels of ApoA-1, ApoC-III, and ApoE were not correlated with SCLC staging. CONCLUSION: ApoA-1 and ApoC-III may be used as differentiating and predictive markers for SCLC. ApoA-1, ApoC-III, and ApoE may be used to monitor the efficacy of chemotherapy. PMID- 26996552 TI - Isoprenaline Induces Periostin Expression in Gastric Cancer. AB - PURPOSE: Periostin mediates critical steps in gastric cancer and is involved in various signaling pathways. However, the roles of periostin in promoting gastric cancer metastasis are not clear. The aim of this study was to investigate the relevance between periostin expression and gastric cancer progression and the role of stress-related hormones in the regulation of cancer development and progression. MATERIALS AND METHODS: Normal, cancerous and metastatic gastric tissues were collected from patients diagnosed with advanced gastric cancer. The in vivo expression of periostin was evaluated by in situ hybridization and immunofluorescent staining. Meanwhile, human gastric adenocarcinoma cell lines MKN-45 and BGC-803 were used to detect the in vitro expression of periostin by using quantitative real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Periostin is expressed in the stroma of the primary gastric tumors and metastases, but not in normal gastric tissue. In addition, we observed that periostin is located mainly in pericryptal fibroblasts, but not in the tumor cells, and strongly correlated to the expression of alpha-smooth muscle actin (SMA). Furthermore, the distribution patterns of periostin were broader as the clinical staging of tumors progressed. We also identified a role of stress related signaling in promoting cancer development and progression, and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. CONCLUSION: These findings suggest that the distribution pattern of periostin was broader as the clinical staging of the tumor progressed and found that isoprenaline upregulated expression levels of periostin in gastric cancer cells. PMID- 26996553 TI - Visually Estimated MRI Targeted Prostate Biopsy Could Improve the Detection of Significant Prostate Cancer in Patients with a PSA Level <10 ng/mL. AB - PURPOSE: To compare prostate cancer detection rates between 12 cores transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and visually estimated multiparametric magnetic resonance imaging (mp-MRI)-targeted prostate biopsy (MRI visual-Bx) for patients with prostate specific antigen (PSA) level less than 10 ng/mL. MATERIALS AND METHODS: In total, 76 patients with PSA levels below 10 ng/mL underwent 3.0 Tesla mp-MRI and TRUS-Bx prospectively in 2014. In patients with abnormal lesions on mp-MRI, we performed additional MRI-visual-Bx. We compared pathologic results, including the rate of clinically significant prostate cancer cores (cancer length greater than 5 mm and/or any Gleason grade greater than 3 in the biopsy core). RESULTS: The mean PSA was 6.43 ng/mL. In total, 48 of 76 (63.2%) patients had abnormal lesions on mp-MRI, and 116 targeted biopsy cores, an average of 2.42 per patient, were taken. The overall detection rates of prostate cancer using TRUS-Bx and MRI-visual-Bx were 26/76 (34.2%) and 23/48 (47.9%), respectively. In comparing the pathologic results of TRUS-Bx and MRI-visual-Bx cores, the positive rates were 8.4% (77 of 912 cores) and 46.6% (54 of 116 cores), respectively (p<0.001). Mean cancer core lengths and mean cancer core percentages were 3.2 mm and 24.5%, respectively, in TRUS-Bx and 6.3 mm and 45.4% in MRI-visual-Bx (p<0.001). In addition, Gleason score >=7 was noted more frequently using MRI-visual-Bx (p=0.028). The detection rate of clinically significant prostate cancer was 27/77 (35.1%) and 40/54 (74.1%) for TRUS-Bx and MRI-visual-Bx, respectively (p<0.001). CONCLUSION: MRI-visual-Bx showed better performance in the detection of clinically significant prostate cancer, compared to TRUS-Bx among patients with a PSA level less than 10 ng/mL. PMID- 26996555 TI - Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer. AB - PURPOSE: To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. MATERIALS AND METHODS: We included 223 patients who received staging laparotomy and were diagnosed with stage IIC-IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. RESULTS: The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). CONCLUSION: Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS. PMID- 26996554 TI - Symptom Interval and Patient Delay Affect Survival Outcomes in Adolescent Cancer Patients. AB - PURPOSE: Unique features of adolescent cancer patients include cancer types, developmental stages, and psychosocial issues. In this study, we evaluated the relationship between diagnostic delay and survival to improve adolescent cancer care. MATERIALS AND METHODS: A total of 592 patients aged 0-18 years with eight common cancers were grouped according to age (adolescents, >=10 years; children, <10 years). We retrospectively reviewed their symptom intervals (SIs, between first symptom/sign of disease and diagnosis), patient delay (PD, between first symptom/sign of disease and first contact with a physician), patient delay proportion (PDP), and overall survival (OS). RESULTS: Mean SI was significantly longer in adolescents than in children (66.4 days vs. 28.4 days; p<0.001), and OS rates were higher in patients with longer SIs (p=0.001). In children with long SIs, OS did not differ according to PDP (p=0.753). In adolescents with long SIs, OS was worse when PDP was >=0.6 (67.2%) than <0.6 (95.5%, p=0.007). In a multivariate analysis, adolescents in the long SI/PDP >=0.6 group tended to have a higher hazard ratio (HR, 6.483; p=0.069) than those in the long SI/PDP <0.6 group (HR=1, reference). CONCLUSION: Adolescents with a long SI/PDP >=0.6 had lower survival rates than those with a short SI/all PDP or a long SI/PDP <0.6. They should be encouraged to seek prompt medical assistance by a physician or oncologist to lessen PDs. PMID- 26996558 TI - Serial Morphological Changes of Side-Branch Ostium after Paclitaxel-Coated Balloon Treatment of De Novo Coronary Lesions of Main Vessels. AB - PURPOSE: The effects on the side-branch (SB) ostium, following paclitaxel-coated balloon (PCB) treatment of de novo coronary lesions of main vessels have not been previously investigated. This study was aimed at evaluating the serial morphological changes of the SB ostium after PCB treatment of de novo coronary lesions of main vessels using optical coherence tomography (OCT). MATERIALS AND METHODS: This prospective, single-center observational study enrolled patients with de novo lesions, which were traversed by at least one SB (>=1.5 mm) and were treated with PCB. The SB ostium was evaluated with serial angiographic and OCT assessments pre- and post-procedure, and at 9-months follow-up. RESULTS: Sixteen main vessel lesions were successfully treated with PCB, and 26 SBs were included for analysis. Mean SB ostial lumen area increased at 9-months follow-up (0.92+/ 0.68 mm2 pre-procedure, 1.03+/-0.77 mm2 post-procedure and 1.42+/-1.18 mm2 at 9 months). The SB ostial lumen area gain was 0.02+/-0.24 mm2 between pre- and post procedure, 0.37+/-0.64 mm2 between post-procedure and 9-months, and 0.60+/-0.93 mm2 between pre-procedure and 9-months. The ostial lumen area increased by 3.9% [interquartile range (IQR) of -33.3 to 10.4%] between pre- and post-procedure, 52.1% (IQR of -0.7 to 77.3%) between post-procedure and 9-months and 76.1% (IQR of 18.2 to 86.6%) between pre-procedure and 9-months. CONCLUSION: PCB treatment of de novo coronary lesions of main vessels resulted in an increase in the SB ostial lumen area at 9-months. PMID- 26996557 TI - Lymphangiogenesis in Breast Cancer Correlates with Matrix Stiffness on Shear-Wave Elastography. AB - PURPOSE: To correlate tumor stiffness and lymphangiogenesis in breast cancer and to find its clinical implications. MATERIALS AND METHODS: A total of 140 breast cancer patients were evaluated. Tumor stiffness was quantitatively measured by shear-wave elastography in preoperative ultrasound examination, calculated as mean elasticity value (kPa). Slides of resected breast cancer specimens were reviewed for most fibrotic area associated with tumor. D2-40 immunohistochemical staining was applied for fibrotic areas to detect the lymphatic spaces. Microlymphatic density, tumor stiffness, and clinicopathologic data were analyzed. RESULTS: Higher elasticity value was associated with invasive size of tumor, microlymphatic density, histologic grade 3, absence of extensive intraductal component, presence of axillary lymph node metastasis, and Ki-67 labeling index (LI) in univariate regression analysis, and associated with Ki-67 LI and axillary lymph node metastasis in multivariate regression analysis. Microlymphatic density was associated histologic grade 3, mean elasticity value, and Ki-67 LI in univariate regression analysis. In multivariate regression analysis, microlymphatic density was correlated with mean elasticity value. CONCLUSION: In breast cancer, tumor stiffness correlates with lymphangiogenesis and poor prognostic factors. PMID- 26996556 TI - Tolfenamic Acid Inhibits the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma: Involvement of p38-Mediated Down-Regulation of Slug. AB - PURPOSE: Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to exhibit antitumor effects in various cancers apart from nasopharyngeal cancer (NPC). NPC exhibits high invasiveness, as well as metastatic potential, and patients continue to suffer from residual, recurrent, or metastatic disease even after chemoradiation therapy. Therefore, new treatment strategies are needed for NPC. In this study, we investigated the efficacy and molecular mechanisms of TA in NPC treatment. MATERIALS AND METHODS: TA-induced cell death was detected by cell viability assay in the NPC cell lines, HNE1 and HONE1. Wound healing assay, invasion assay, and Western blot analysis were used to evaluate the antitumor effects of TA in NPC cell lines. RESULTS: Treatment with TA suppressed the migration and invasion of HNE1 and HONE1 cells. Hepatocyte growth factor enhanced the proliferation, migration, and invasion abilities of NPC cells. This enhancement was successfully inhibited by TA treatment. Treatment with TA increased phosphorylation of p38, and the inhibition of p38 with SB203580 reversed the cytotoxic, anti-invasive, and anti-migratory effects of TA treatment in NPC cell lines. Moreover, inhibition of p38 also reversed the decrease in expression of Slug that was induced by TA treatment. CONCLUSION: In conclusion, the activation of p38 plays a role in mediating TA-induced cytotoxicity and inhibition of invasion and migration via down-regulation of Slug. PMID- 26996559 TI - Association between the Red Cell Distribution Width and Vasospastic Angina in Korean Patients. AB - PURPOSE: The association between the red cell distribution width (RDW) and vasospastic angina (VSA) has not been elucidated. We investigated the association of the RDW with the incidence and angiographic subtypes of VSA in Korean patients. MATERIALS AND METHODS: A total of 460 patients who underwent intracoronary ergonovine provocation tests were consecutively enrolled and classified into two groups: the VSA group (n=147, 32.0%) and non-VSA group (n=313, 68.0%). The subjects were classified into 3 subgroups (tertiles) according to the baseline level of RDW assessed before the angiographic provocation test. RESULTS: The VSA group had a higher RDW than the non-VSA group (12.9+/-0.8% vs. 12.5+/-0.7%, p=0.013). The high RDW level demonstrated an independent association with the high incidence of VSA [second tertile: hazard ratio (HR) 1.96 (1.13-2.83), third tertile: HR 2.33 (1.22-3.47), all p<0.001]. Moreover, the highest RDW tertile level had a significant association with the prevalence of the mixed-type coronary spasm [HR 1.29 (1.03-1.59), p=0.037]. CONCLUSION: The high level of RDW was significantly associated with the prevalence of VSA and the high-risk angiographic subtype of coronary spasm, suggesting that a proactive clinical investigation for VSA could be valuable in Korean patients with an elevated RDW. PMID- 26996560 TI - Comparison of Outcomes after Device Closure and Medication Alone in Patients with Patent Foramen Ovale and Cryptogenic Stroke in Korean Population. AB - PURPOSE: To compare the effectiveness of device closure and medical therapy in prevention of recurrent embolic event in the Korean population with cryptogenic stroke and patent foramen ovale (PFO). MATERIALS AND METHODS: Consecutive 164 patients (men: 126 patients, mean age: 48.1 years, closure group: 72 patients, medical group: 92 patients) were enrolled. The primary end point was a composite of death, stroke, transient ischemic attack (TIA), or peripheral embolism. RESULTS: Baseline characteristics were similar in the two groups, except age, which was higher in the medical group (45.3+/-9.8 vs. 50.2+/-6.1, p<0.0001), and risk of paradoxical embolism score, which was higher in the closure group (6.2+/ 1.6 vs. 5.7+/-1.3, p=0.026). On echocardiography, large right-to-left shunt (81.9% vs. 63.0%, p=0.009) and shunt at rest/septal hypermobility (61.1% vs. 23.9%, p<0.0001) were more common in the closure group. The device was successfully implanted in 71 (98.6%) patients. The primary end point occurred in 2 patients (2 TIA, 2.8%) in the closure group and in 2 (1 death, 1 stroke, 2.2%) in the medical group. Event-free survival rate did not differ between the two groups. CONCLUSION: Compared to medical therapy, device closure of PFO in patients with cryptogenic stroke did not show difference in reduction of recurrent embolic events in the real world's setting. However, considering high risk of echocardiographic findings in the closure group, further investigation of the role of PFO closure in the Asian population is needed. PMID- 26996561 TI - Outcomes before and after the Implementation of a Critical Pathway for Patients with Acute Aortic Disease. AB - PURPOSE: Acute aortic diseases, such as aortic dissection and aortic aneurysm, can be life-threatening vascular conditions. In this study, we compared outcomes before and after the implementation of a critical pathway (CP) for patients with acute aortic disease at the emergency department (ED). MATERIALS AND METHODS: This was a retrospective observational cohort study. The CP was composed of two phases: PRE-AORTA for early diagnosis and AORTA for prompt treatment. We compared patients who were diagnosed with acute aortic disease between pre-period (January 2010 to December 2011) and post-period (July 2012 to June 2014). RESULTS: Ninety four and 104 patients were diagnosed with acute aortic disease in the pre- and post-periods, respectively. After the implementation of the CP, 38.7% of acute aortic disease cases were diagnosed via PRE-AORTA. The door-to-CT time was reduced more in PRE-AORTA-activated patients [71.0 (61.0, 115.0) min vs. 113.0 (56.0, 170.5) min; p=0.026]. During the post-period, more patients received emergency intervention than during the pre-period (22.3% vs. 36.5%; p=0.029). Time until emergency intervention was reduced in patients, who visited the ED directly, from 378.0 (302.0, 489.0) min in the pre-period to 200.0 (170.0, 299.0) min in the post-period (p=0.001). The number of patients who died in the ED declined from 11 to 4 from the pre-period to the post-period. Hospital mortality decreased from 26.6% to 14.4% in the post-period (p=0.033). CONCLUSION: After the implementation of a CP for patients with acute aortic disease, more patients received emergency intervention within a shorter time, resulting in improved hospital mortality. PMID- 26996562 TI - Development and Comparison of Warfarin Dosing Algorithms in Stroke Patients. AB - PURPOSE: The genes for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) have been identified as important genetic determinants of warfarin dosing and have been studied. We developed warfarin algorithm for Korean patients with stroke and compared the accuracy of warfarin dose prediction algorithms based on the pharmacogenetics. MATERIALS AND METHODS: A total of 101 patients on stable maintenance dose of warfarin were enrolled. Warfarin dosing algorithm was developed using multiple linear regression analysis. The performance of all the algorithms was characterized with coefficient of determination, determined by linear regression, and the mean of percent deviation was used to predict doses from the actual dose. In addition, we compared the performance of the algorithms using percentage of predicted dose falling within +/-20% of clinically observed doses and dividing the patients into a low-dose group (<=3 mg/day), an intermediate-dose group (3-7 mg/day), and high dose group (>=7 mg/day). RESULTS: A new developed algorithms including the variables of age, body weight, and CYP2C9 and VKORC1 genotype. Our algorithm accounted for 51% of variation in the warfarin stable dose, and performed best in predicting dose within 20% of actual dose and intermediate-dose group. CONCLUSION: Our warfarin dosing algorithm may be useful for Korean patients with stroke. Further studies to elucidate clinical utility of genotype-guided dosing and find the additional genetic association are necessary. PMID- 26996563 TI - The Resistance Mechanism and Clonal Distribution of Tigecycline-Nonsusceptible Klebsiella pneumoniae Isolates in Korea. AB - PURPOSE: Tigecycline is one of the drugs used to treat multi-drug resistant Klebsiella pneumoniae (K. pneumoniae) infections, including complicated skin and soft tissue infections, complicated intra-abdominal infection, and community acquired pneumonia in the Republic of Korea. However, since its commercial release, K. pneumoniae resistance against tigecycline has been reported, and there is a serious concern about the spread of tigecycline resistant bacteria. MATERIALS AND METHODS: In this study, we collected and analyzed 342 isolates from 23 hospitals in the Republic of Korea to determine the mechanisms of tigecycline susceptibility and their clonal types. The hospitals include several from each province in the Republic of Korea, except Jeju, an island province, and nonsusceptibility among the isolates was tested by the disk diffusion method. In our lab, susceptibility was checked again using the broth dilution method, and clonal types were determined using the multilocus sequence typing protocol. Real time PCR was performed to measure the ramR mutation in the isolates nonsusceptible to tigecycline, which would suggest an increased expression of the AcrAB multidrug pump. RESULTS: Fifty-six K. pneumoniae isolates were found to be nonsusceptible, 16% of the 342 collected. Twenty-seven and nine isolates of the tigecycline nonsusceptible isolates had mutations in the ramR and rpsJ genes, respectively; while 18 nonsusceptible isolates harbored the tetA gene. Comparison of isolates with and without ramR mutation showed a significant statistical difference (p<0.05) for expression of AcrAB. Moreover, the most common clonal types, as observed in our study, appear to be ST11 and ST789. CONCLUSION: Several dominate clonal types infer tigecycline resistance to K. pneumoniae, including ST11, ST768, ST15, ST23, ST48, and ST307. There does not seem to be a transferrable medium, such as plasmid, for the resistance yet, although mutation of the ramR gene may be a common event, accounting for 48% of the nonsusceptibility in this study. PMID- 26996564 TI - Activation of NF-kappaB and AP-1 Mediates Hyperproliferation by Inducing beta Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells. AB - PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as beta-catenin and c-myc. Even though transcription factors NF-kappaB and AP-1 are activated in H. pylori-infected cells, whether NF-kappaB or AP-1 regulates the expression of beta-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori induced activation of NF-kappaB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IkappaBalpha (MAD3) and c-Jun (TAM67) or treated with a specific NF-kappaB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR 11302 to suppress activation of NF-kappaB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-kappaB and AP-1, cell proliferation, and expression of oncogenes (beta-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-kappaB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR 11302 inhibited cell proliferation and expression of oncogenes in H. pylori infected cells. CONCLUSION: H. pylori-induced activation of NF-kappaB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells. PMID- 26996565 TI - Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B. AB - PURPOSE: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T cell cytotoxic proteins in patients with AHA or AHB to identify liver injury associated cytokines. MATERIALS AND METHODS: Forty-six patients with AHA, 16 patients with AHB, and 14 healthy adults were enrolled in the study. Serum levels of 17 cytokines and T-cell cytotoxic proteins were measured by enzyme-linked immunosorbent assays or cytometric bead arrays and analyzed for correlation with serum alanine aminotransferase (ALT) levels. RESULTS: Interleukin (IL)-18, IL-8, CXCL9, and CXCL10 were significantly elevated in both AHA and AHB. IL-6, IL-22, granzyme B, and soluble Fas ligand (sFasL) were elevated in AHA but not in AHB. In both AHA and AHB, the serum level of CXCL10 significantly correlated with the peak ALT level. Additionally, the serum level of granzyme B in AHA and the serum level of sFasL in AHB correlated with the peak ALT level. CONCLUSION: We identified cytokines and T-cell cytotoxic proteins associated with liver injury in AHA and AHB. These findings deepen the existing understanding of immunological mechanisms responsible for liver injury in acute viral hepatitis. PMID- 26996566 TI - Waist-to-Height Ratio as an Index for Cardiometabolic Risk in Adolescents: Results from the 1998-2008 KNHANES. AB - PURPOSE: To describe the relationship between the waist-to-height ratio (WHtR) and cardiometabolic risk factors (CMRFs) and to evaluate the validity of WHtR in identifying adolescents with metabolic syndrome. MATERIALS AND METHODS: We analyzed data from a pooled population of 4068 adolescents aged 10-19 years from the Korean National Health and Nutrition Examination Surveys conducted between 1998 and 2008. Overweight individuals were defined by body mass index (BMI) >=85th percentile. Those with at least 2 CMRFs among hypertension, hyperglycemia, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol (HDL-C) were classified as having multiple CMRFs. RESULTS: WHtR was significantly related to systolic blood pressure, HDL-C, and triglycerides in both non-overweight and overweight adolescents (all p<0.01). Among overweight adolescents, the area under the curve (AUC) for WHtR in identifying multiple CMRFs was significantly greater than that for BMI (p=0.014). Metabolic syndrome was more common in overweight adolescents with a WHtR of >=0.5 than in those with a WHtR of <0.5 (p<0.001). In non-overweight adolescents, the prevalences of multiple CMRFs (p=0.001) and metabolic syndrome (p<0.001) were higher in those with a WHtR of >=0.5 than in those with a WHtR of <0.5. Among those without central obesity, the prevalence of multiple CMRFs was higher in those with a WHtR of >=0.5 than in those with a WHtR of <0.5 (p=0.021). CONCLUSION: WHtR is a simple and valid index for identifying adolescents with increased cardiometabolic risk and is related to CMRFs even in non-overweight adolescents. In adolescents already screened via BMI and waist circumference (WC), WHtR seems to be of additional help in discriminating those at higher cardiometabolic risk. PMID- 26996567 TI - Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy. AB - PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway. PMID- 26996568 TI - Visceral Fat Mass Has Stronger Associations with Diabetes and Prediabetes than Other Anthropometric Obesity Indicators among Korean Adults. AB - PURPOSE: This study determined which obesity measurement correlates the best with diabetes and prediabetes. MATERIALS AND METHODS: This cross-sectional study enrolled 1603 subjects (611 men, 992 women; age 30-64 years) at the Cardiovascular and Metabolic Diseases Etiology Research Center. Body mass index, waist circumference, waist-height ratio, waist-hip ratio, waist-thigh ratio, and visceral fat were used as measures of obesity. Visceral fat was acquired using dual-energy X-ray absorptiometry (DXA). The prevalences of diabetes and prediabetes were defined using the criteria in the American Diabetes Association 2015 guidelines. RESULTS: After adjusting for age and other potential confounding factors, participants with a visceral fat mass in the upper 10th percentile had a higher odds ratio (OR) for diabetes and prediabetes than the upper 10th percentile of other adiposity indices [men, OR=15.9, 95% confidence interval (CI)=6.4-39.2; women, OR=6.9, 95% CI=3.5-13.7]. Visceral fat mass also had the highest area under the curve with diabetes and prediabetes in both men (0.69, 95% CI=0.64-0.73) and women (0.70, 95% CI=0.67-0.74) compared to other anthropometric measurements of obesity. CONCLUSION: Visceral fat mass measured using DXA is an indicator of diabetes or prediabetes, due to its ability to differentiate between abdominal visceral and subcutaneous fat. PMID- 26996569 TI - Soy Protein Supplementation Reduces Clinical Indices in Type 2 Diabetes and Metabolic Syndrome. AB - PURPOSE: Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. RESULTS: The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessment for insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, 0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, 0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (>=6 mo) significantly reduced FPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. CONCLUSION: Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma. PMID- 26996570 TI - High-Sensitivity C-Reactive Protein Can Reflect Small Airway Obstruction in Childhood Asthma. AB - PURPOSE: High-sensitivity assays enabled the identification of C-reactive protein (hs-CRP) at levels that were previously undetectable. We aimed to determine if hs CRP could reflect airway inflammation in children, by comparing hs-CRP with spirometry and impulse oscillometry (IOS) parameters and symptomatic severities. MATERIALS AND METHODS: A total of 276 asthmatic children who visited Severance Children's Hospital from 2012-2014 were enrolled. Serum hs-CRP and pulmonary function tests were performed on the same day. Patients were divided into hs-CRP positive and negative groups (cut-off value, 3.0 mg/L). RESULTS: Of the 276 asthmatic children [median age 7.5 (5.9/10.1) years, 171 boys (62%)], 39 were hs CRP positive and 237 were negative. Regarding spirometry parameters, we observed significant differences in maximum mid-expiratory flow, % predicted (FEF25-75) (p=0.010) between hs-CRP positive and negative groups, and a negative correlation between FEF25-75 and hs-CRP. There were significant differences in the reactance area (AX) (p=0.046), difference between resistance at 5 Hz and 20 Hz (R5-R20) (p=0.027), resistance at 5 Hz, % predicted (R5) (p=0.027), and reactance at 5 Hz, % predicted (X5) (p=0.041) between hs-CRP positive and negative groups. There were significant positive correlations between hs-CRP and R5 (r=0.163, p=0.008), and X5 (r=0.164, p=0.007). Spirometry and IOS parameters had more relevance in patients with higher blood neutrophil levels in comparison to hs-CRP. CONCLUSION: Hs-CRP showed significant correlation with FEF25-75, R5, and X5. It can reflect small airway obstruction in childhood asthma, and it is more prominent in neutrophil dominant inflammation. PMID- 26996572 TI - A Six-Year Study on the Changes in Airborne Pollen Counts and Skin Positivity Rates in Korea: 2008-2013. AB - PURPOSE: The occurrence of pollen allergy is subject to exposure to pollen, which shows regional and temporal variations. We evaluated the changes in pollen counts and skin positivity rates for 6 years, and explored the correlation between their annual rates of change. MATERIALS AND METHODS: We assessed the number of pollen grains collected in Seoul, and retrospectively reviewed the results of 4442 skin prick tests conducted at the Severance Hospital Allergy-Asthma Clinic from January 1, 2008 to December 31, 2013. RESULTS: For 6 years, the mean monthly total pollen count showed two peaks, one in May and the other in September. Pollen count for grasses also showed the same trend. The pollen counts for trees, grasses, and weeds changed annually, but the changes were not significant. The annual skin positivity rates in response to pollen from grasses and weeds increased significantly over the 6 years. Among trees, the skin positivity rates in response to pollen from walnut, popular, elm, and alder significantly increased over the 6 years. Further, there was a significant correlation between the annual rate of change in pollen count and the rate of change in skin positivity rate for oak and hop Japanese. CONCLUSION: The pollen counts and skin positivity rates should be monitored, as they have changed annually. Oak and hop Japanese, which showed a significant correlation with the annual rate of change in pollen count and the rate of change in skin positivity rate over the 6 years may be considered the major allergens in Korea. PMID- 26996571 TI - Near-Road Exposure and Impact of Air Pollution on Allergic Diseases in Elementary School Children: A Cross-Sectional Study. AB - PURPOSE: The study aims to classify schools based on traffic pollutants and their complex sources, to assess the environment, to determine the state of allergic diseases among students using the International Study of Asthma and Allergies in children (ISAAC) questionnaire, and to assess their connection to air pollutants. MATERIALS AND METHODS: A total of seven schools were divided into three categories according to the characteristics of their surrounding environments: three schools in traffic-related zones, two schools in complex source zones I (urban), and two schools in complex source zones II (industrial complex). ISAAC questionnaires were administered and the 4404 completed questionnaires were analyzed. RESULTS: The frequency of asthma treatment during the past 12 months showed a significant increase (p<0.05) with exposure to NO2 [1.67, 95% confidence intervals (CIs) 1.03-2.71] in the complex source zones. The frequency of allergic rhinitis treatment during the past 12 months increased significantly with exposure to Black Carbon (1.60, 95% CIs 1.36-1.90) (p<0.001), SO2 (1.09, 95% CIs 1.01-1.17) (p<0.05), NO2 (1.18, 95% CIs 1.07-1.30) (p<0.01) for all subjects. CONCLUSION: In terms of supporting children's health, care, and prevention related to major spaces for children, such as school zones, spaces used in coming to and leaving school, playgrounds, and classrooms are essential to ensuring not only the safety of children from traffic accidents but also their protection from local traffic pollutants and various hazardous environmental factors. PMID- 26996573 TI - Association between the Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Alexithymia in Patients with Obsessive-Compulsive Disorder. AB - PURPOSE: Alexithymia, defined as a deficit in the ability to recognize and describe one's own feelings, may be related to the development and maintenance of obsessive-compulsive symptoms. The aim of this study was to evaluate the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and alexithymia in patients with obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: We recruited 244 patients with OCD (169 males, 75 females). Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20), and genotyping of the COMT Val158Met polymorphism was evaluated. RESULTS: Patients with the COMT Val/Val genotype had significantly higher total and "difficulty identifying feelings" (DIF) subdimension scores than those with the Val/Met or Met/Met genotypes. Patients with the COMT Val/Val genotype had significantly higher "difficulty describing feelings" (DDF) subdimension scores than those with the COMT Val/Met genotype. However, there were no differences in the scores for the "externally oriented thinking" (EOT) subdimension among the three genotypes. CONCLUSION: These results indicate that the high-activity Val allele of the COMT Val158Met polymorphism is associated with increased alexithymic traits in patients with OCD. The present finding suggests that alexithymia is an endophenotype of OCD that is mediated by the COMT Val158Met polymorphism. PMID- 26996574 TI - The Applicability of Trauma and Injury Severity Score for a Blunt Trauma Population in Korea and a Proposal of New Models Using Score Predictors. AB - PURPOSE: The purpose of this study was to verify the utility of existing Trauma and Injury Severity Score (TRISS) coefficients and to propose a new prediction model with a new set of TRISS coefficients or predictors. MATERIALS AND METHODS: Of the blunt adult trauma patients who were admitted to our hospital in 2014, those eligible for Korea Trauma Data Bank entry were selected to collect the TRISS predictors. The study data were input into the TRISS formula to obtain "probability of survival" values, which were examined for consistency with actual patient survival status. For TRISS coefficients, Major Trauma Outcome Study derived values revised in 1995 and National Trauma Data Bank-derived and National Sample Project-derived coefficients revised in 2009 were used. Additionally, using a logistic regression method, a new set of coefficients was derived from our medical center's database. Areas under the receiver operating characteristic (ROC) curve (AUC) for each prediction ability were obtained, and a pairwise comparison of ROC curves was performed. RESULTS: In the statistical analysis, the AUCs (0.879-0.899) for predicting outcomes were lower than those of other countries. However, by adjusting the TRISS score using a continuous variable rather than a code for age, we were able to achieve higher AUCs [0.913 (95% confidence interval, 0.899 to 0.926)]. CONCLUSION: These results support further studies that will allow a more accurate prediction of prognosis for trauma patients. Furthermore, Korean TRISS coefficients or a new prediction model suited for Korea needs to be developed using a sufficiently sized sample. PMID- 26996575 TI - The Relationship between HIF-2alpha and VEGF with Radiographic Severity in the Primary Osteoarthritic Knee. AB - PURPOSE: The aim of this study was to determine the relationship of hypoxia inducible factor-2 (HIF-2alpha) and vascular endothelial growth factor (VEGF) with radiographic severity in primary osteoarthritis (OA) of the knee. Expression of these two factors in cartilage samples from OA knee joints was examined at mRNA and protein levels. MATERIALS AND METHODS: Knee joints were examined using plain radiographs, and OA severity was assessed using the Kellgren and Lawrence (KL) grading system. Specimens were collected from 29 patients (31 knees) who underwent total knee replacement because of severe medial OA of the knee (KL grades 3 and 4), 16 patients who underwent knee arthroscopy (KL grade 2), and 5 patients with traumatic knees (KL grade 0). HIF-2alpha and VEGF expression was quantified by real-time polymerase chain reaction and western blotting. RESULTS: Cartilage degeneration correlated with the radiographic severity grade. OA severity, determined using the Mankin scale, correlated positively with the KL grade (r=0.8790, p<0.01), and HIF-2alpha and VEGF levels with the radiographic severity of knee OA (r=0.7001, p<0.05; r=0.6647, p<0.05). CONCLUSION: In OA cartilage, HIF-2alpha and VEGF mRNA and protein levels were significantly and positively correlated. The expression of both factors correlated positively with the KL grade. HIF-2alpha and VEGF, therefore, may serve as biochemical markers as well as potential therapeutic targets in knee OA. PMID- 26996576 TI - Point-Connecting Measurements of the Hallux Valgus Deformity: A New Measurement and Its Clinical Application. AB - PURPOSE: The aim of this study was to investigate new point-connecting measurements for the hallux valgus angle (HVA) and the first intermetatarsal angle (IMA), which can reflect the degree of subluxation of the first metatarsophalangeal joint (MTPJ). Also, this study attempted to compare the validity of midline measurements and the new point-connecting measurements for the determination of HVA and IMA values. MATERIALS AND METHODS: Sixty feet of hallux valgus patients who underwent surgery between 2007 and 2011 were classified in terms of the severity of HVA, congruency of the first MTPJ, and type of chevron metatarsal osteotomy. On weight-bearing dorsal-plantar radiographs, HVA and IMA values were measured and compared preoperatively and postoperatively using both the conventional and new methods. RESULTS: Compared with midline measurements, point-connecting measurements showed higher inter- and intra-observer reliability for preoperative HVA/IMA and similar or higher inter- and intra-observer reliability for postoperative HVA/IMA. Patients who underwent distal chevron metatarsal osteotomy (DCMO) had higher intraclass correlation coefficient for inter- and intra-observer reliability for pre- and post-operative HVA and IMA measured by the point-connecting method compared with the midline method. All differences in the preoperative HVAs and IMAs determined by both the midline method and point-connecting methods were significant between the deviated group and subluxated groups (p=0.001). CONCLUSION: The point-connecting method for measuring HVA and IMA in the subluxated first MTPJ may better reflect the severity of a HV deformity with higher reliability than the midline method, and is more useful in patients with DCMO than in patients with proximal chevron metatarsal osteotomy. PMID- 26996577 TI - Efficacy of Anti-NaV1.7 Antibody on the Sensory Nervous System in a Rat Model of Lumbar Intervertebral Disc Injury. AB - PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. RESULTS: The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). CONCLUSION: NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration. PMID- 26996578 TI - The Role of Steroid Sulfatase as a Prognostic Factor in Patients with Endometrial Cancer. AB - PURPOSE: The aim of the study was to determine steroid sulfatase (STS) expression in endometrial cancer patients and its correlation with disease prognosis. MATERIALS AND METHODS: We conducted a retrospective study in 59 patients who underwent surgery with histologically confirmed endometrial cancer from January 2000 to December 2011 at Hanyang University Hospital. Immuno-histochemical staining of STS was performed using rabbit polyclonal anti-STS antibody. RESULTS: Sixteen of the 59 patients (27.1%) were positive for STS expression. Disease free survival (DFS) was 129.83+/-8.67 [95% confidence interval (CI): 112.84-146.82] months in the STS positive group (group A) and 111.06+/-7.17 (95% CI: 97.01 125.10) months in the STS negative group (group B) (p=0.92). Overall survival (OS) was 129.01+/-9.38 (95% CI: 110.63-147.38) months and 111.16+/-7.10 (95% CI: 97.24-125.07) months for the groups A and B, respectively (p=0.45). Univariate analysis revealed that FIGO stage and adjuvant therapy are significantly associated with DFS and OS. However, in multivariate analysis, FIGO stage and adjuvant therapy did not show any statistical significance with DFS and OS. STS was also not significantly associated with DFS and OS in univariate and multivariate analysis. CONCLUSION: STS expression was not significantly associated with DFS and OS, despite positive STS expression in 27% of endometrial cancer patients. Therefore, the role of STS as a prognostic factor in patients with endometrial cancer remains unclear and requires further research. PMID- 26996579 TI - STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9. AB - PURPOSE: Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanisms associated with these events in the immortalized human trophoblast cell line HTR8/SVneo. MATERIALS AND METHODS: We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasion activity were further determined via Western blot and gelatin zymography. RESULTS: OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increased invasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extent by STAT3 inhibition. CONCLUSION: Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activation of STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells. PMID- 26996580 TI - Change in Pulmonary Function after Incentive Spirometer Exercise in Children with Spastic Cerebral Palsy: A Randomized Controlled Study. AB - PURPOSE: The aim of this study was to investigate the effect of incentive spirometer exercise (ISE) on pulmonary function and maximal phonation time (MPT) in children with spastic cerebral palsy (CP). MATERIALS AND METHODS: Fifty children with CP were randomly assigned to two groups: the experimental group and the control group. Both groups underwent comprehensive rehabilitation therapy. The experimental group underwent additional ISE. The forced vital capacity (FVC), forced expiratory volume at one second (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF), and MPT were assessed as outcome measures before and after 4 weeks of training. RESULTS: There were significant improvements in FVC, FEV1, PEF, and MPT in the experimental group, but not in the control group. In addition, the improvements in FVC, FEV1, and MPT were significantly greater in the experimental group than in the control group. CONCLUSION: The results of this randomized controlled study support the use of ISE for enhancing pulmonary function and breath control for speech production in children with CP. PMID- 26996582 TI - Potential Relationship between Season of Birth and Clinical Characteristics in Major Depressive Disorder in Koreans: Results from the CRESCEND Study. AB - We aimed to examine the potential relationship between season of birth (SOB) and clinical characteristics in Korean patients with unipolar non-psychotic major depressive disorder (MDD). Using data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, 891 MDD patients were divided into two groups, those born in spring/summer (n=457) and those born in autumn/winter (n=434). Measurement tools comprising the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Scale for Suicidal Ideation, Clinical Global Impression of severity, Social and Occupation Functional Assessment Scale, WHO Quality of Life assessment instrument abbreviated version, Alcohol Use Disorder Identification Test, and Temperament and Character Inventory were used to evaluate depression, anxiety, overall symptoms, suicidal ideation, global severity, social function, quality of life, drinking, and temperament and character, respectively. Using independent t-tests for continuous variables and chi2 tests for discrete variables, the clinical characteristics of the two groups were compared. MDD patients born in spring/summer were on average younger at onset of first depressive episode (t=2.084, p=0.038), had greater loss of concentration (chi2=4.589, p=0.032), and were more self-directed (t=2.256, p=0.025) than those born in autumn/winter. Clinically, there was a trend for the MDD patients born in spring/summer to display the contradictory characteristics of more severe clinical course and less illness burden; this may have been partly due to a paradoxical effect of the 5-HT system. PMID- 26996581 TI - Risk Factors of Acoustic Neuroma: Systematic Review and Meta-Analysis. AB - PURPOSE: Many epidemiological studies have investigated environmental risk factors for the development of acoustic neuroma. However, these results are controversial. We conducted a meta-analysis of case-control studies to identify any potential relationship between history of noise exposure, smoking, allergic diseases, and risk of acoustic neuroma. MATERIALS AND METHODS: We searched PubMed to identify relevant articles. Two researchers evaluated the eligibility and extracted the data independently. RESULTS: Eleven case-control studies were included in our meta-analysis. Acoustic neuroma was found to be associated with leisure noise exposure [odds ratio (OR)=1.33, 95% confidence interval (CI): 1.05 1.68], but not with occupational noise exposure and ever noise exposure (OR=1.20, 95% CI: 0.84-1.72 and OR=1.15, 95% CI: 0.80-1.65). The OR of acoustic neuroma for ever (versus never) smoking was 0.53 (95% CI: 0.30-0.94), while the subgroup analysis indicated ORs of 0.95 (95% CI: 0.81-1.10) and 0.49 (95% CI: 0.41-0.59) for ex-smoker and current smoker respectively. The ORs for asthma, eczema, and seasonal rhinitis were 0.98 (95% CI: 0.80-1.18), 0.91 (95% CI: 0.76-1.09), and 1.52 (95% CI: 0.90-2.54), respectively. CONCLUSION: Our meta-analysis is suggestive of an elevated risk of acoustic neuroma among individuals who were ever exposed to leisure noise, but not to occupational noise. Our study also indicated a lower acoustic neuroma risk among ever and current cigarette smokers than never smokers, while there was no significant relationship for ex-smokers. No significant associations were found between acoustic neuroma and history of any allergic diseases, such as asthma, eczema, and seasonal rhinitis. PMID- 26996583 TI - Simple Purification of Adeno-Associated Virus-DJ for Liver-Specific Gene Expression. AB - Recombinant gene expression using adeno-associated viruses (AAVs) has become a valuable tool in animal studies, as they mediate safe expression of transduced genes for several months. The liver is a major organ of metabolism, and liver specific expression of a gene can be an invaluable tool for metabolic studies. AAV-DJ is a recombinant AAV generated by the gene shuffling of various AAV serotypes and shares characteristics of AAV2 and AAV8. AAV-DJ contains a heparin binding domain in its capsid, which suggests that a heparin column could be used for the purification of the AAV. Given that AAV-DJ has been only recently available, relatively little is known about the optimal preparation/purification and application of AAV-DJ. Here, we present a simple large-scale preparation method that can generate 3*1013 viral particles for in vivo experiments and demonstrate liver-specific gene expression via systemic injection in mice. PMID- 26996584 TI - Graves' Patient with Thymic Expression of Thyrotropin Receptors and Dynamic Changes in Thymic Hyperplasia Proportional to Graves' Disease Activity. AB - Thymic hyperplasia is frequently observed in Graves' disease. However, detectable massive enlargement of the thymus is rare, and the mechanism of its formation has remained elusive. This case showed dynamic changes in thymic hyperplasia on serial computed tomography images consistent with changes in serum thyrotropin receptor (TSH-R) antibodies and thyroid hormone levels. Furthermore, the patient's thymic tissues underwent immunohistochemical staining for TSH-R, which demonstrated the presence of thymic TSH-R. The correlation between serum TSH-R antibody levels and thymic hyperplasia sizes and the presence of TSH-R in her thymus suggest that TSH-R antibodies could have a pathogenic role in thymic hyperplasia. PMID- 26996585 TI - Platypnea-Orthodeoxia Syndrome Two Decades after Definitive Surgical Repair of Pulmonary Atresia with Intact Ventricular Septum. AB - A 20-year-old female had undergone definitive surgical repair for pulmonary atresia with intact ventricular septum soon after birth. She was referred to our institution with the chief complaint of clubbing fingers. A thorough examination revealed platypnea-orthodeoxia syndrome due to an interatrial right-to-left shunt through a secundum atrial septal defect. Percutaneous closure with an Amplatzer Septal Occluder resulted in resolution of the syndrome. PMID- 26996586 TI - Levosulpiride-Associated Hemichorea. PMID- 26996587 TI - Erratum to "Risk Factors for Osteoarthritis and Contributing Factors to Current Arthritic Pain in South Korean Older Adults" by Lee KM, et al. (Yonsei Med J 2015;56:124-31.). PMID- 26996588 TI - Erratum to "Relationships between Isometric Muscle Strength, Gait Parameters, and Gross Motor Function Measure in Patients with Cerebral Palsy" by Shin HI, et al. (Yonsei Med J 2016;57:217-24.). PMID- 26996589 TI - Comparative results of gastric banding in adolescents and young adults. AB - BACKGROUND/PURPOSE: Obesity has become a major public health priority. Because of disappointing results obtained with dietary and medical programs, bariatric surgery has been offered to adolescents, although this practice remains controversial. Our aim was to evaluate laparoscopic adjustable gastric banding (LAGB) in adolescents at 2-year follow-up. MATERIAL AND METHODS: This prospective study, from 2008 to 2013, compared results between adolescent patients and young adult controls. The LAGB technique and the follow-up program were similar. Weight loss and comorbid disease were analyzed. RESULTS: Thirty-six adolescents (mean age at surgery=16.7+/-1.3years) were operated on and compared to 53 young adults (mean age at surgery=21.7+/-1.9years). The mean weight and BMI at surgery were 124.4+/-20.7 and 43.9+/-5.5kg/m(2), respectively. Among the adolescents, none were diabetic or hypertensive. The mean glycated hemoglobin was 5.6+/-1.2%. In four cases (11%) dyslipidemia was observed. There was no significant difference between the two groups in terms of initial preoperative weight or BMI. The absolute BMI values at 6, 12 and 24months after surgery were comparable between adolescents and young adults: 38.7 vs 39.8, 36.0 vs 37.6 and 33.5 vs 36.1kg/m(2), respectively. The excess weight loss was higher in adolescents at 12 and 24months: 48.6 vs 37.6% (p=0.03); and 62.3 vs 45.5% (p=0.02). During this period, insulin resistance and dyslipidemia decreased similarly in both groups. CONCLUSION: Provided there is careful selection of patients and a supportive multidisciplinary team, satisfying results can be obtained after LAGB in adolescents, comparable to those obtained in young adults at 2-year follow-up. PMID- 26996590 TI - Decreased expression of monocarboxylate transporter 1 and 4 in the branching airway epithelium of nitrofen-induced congenital diaphragmatic hernia. AB - BACKGROUND/PURPOSE: Monocarboxylate transporters (MCTs) are crucial for the maintenance of intracellular pH homeostasis in developing fetal lungs. MCT1/4 is strongly expressed by epithelial airway cells throughout lung branching morphogenesis. Functional inhibition of MCT1/4 in fetal rat lung explants has been shown to result in airway defects similar to pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). We hypothesized that pulmonary expression of MCT1/4 is decreased during lung branching morphogenesis in the nitrofen model of CDH-associated PH. METHODS: Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D15, D18, and D21, and divided into control and nitrofen-exposed group. Pulmonary gene expression levels of MCT1/4 were analyzed by qRT-PCR. Immunofluorescence staining for MCT1/4 was combined with E-cadherin in order to evaluate protein expression in branching airway tissue. RESULTS: Relative mRNA levels of MCT1/4 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Confocal laser scanning microscopy confirmed markedly decreased immunofluorescence of MCT1/4 in distal bronchial and primitive alveolar epithelium of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. CONCLUSION: Decreased expression of MCT1/4 in distal airway epithelium may disrupt lung branching morphogenesis and thus contribute to the development of PH in the nitrofen-induced CDH model. PMID- 26996591 TI - Wound classification in pediatric surgical procedures: Measured and found wanting. AB - PURPOSE: Surgical wound classification has emerged as a measure of surgical quality of care, but scant data exist in the era of minimally invasive procedures, especially in children. The aim of this study is to examine the surgical site infection (SSI) rate by wound classification during common pediatric surgical procedures. METHODS: A retrospective analysis of the 2013 Pediatric-National Surgical Quality Improvement Program (Peds-NSQIP) dataset was conducted. Patients undergoing pyloromyotomy, cholecystectomy, ostomy reversal, and appendectomy were included. Wound classification, SSI rate, reoperation, and readmission were analyzed. RESULTS: A total of 10,424 records were included. Pyloromyotomy, a clean case, had a 0.7% SSI rate, while ostomy reversal, a clean contaminated case, had an SSI in 6.9% of cases. Appendectomy for nonperforated acute appendicitis and laparoscopic cholecystectomy for cholecystitis, both contaminated cases, had SSI rates of 2.1% and <1%, respectively. Appendectomy for perforated appendicitis, a dirty procedure, had a 9.1% SSI rate, below the expected >40% for dirty cases. Reoperations and readmission rates ranged from <1% to 9% and increased with case complexity. CONCLUSION: Current wound classifications systems do not reflect surgical risk in children and remain questionable tools for benchmarking surgical care in children. Role of readmissions and reoperations as quality of care indices needs further investigation. PMID- 26996592 TI - Early transition to oral antibiotics for treatment of perforated appendicitis in pediatric patients: Confirmation of the safety and efficacy of a growing national trend. AB - PURPOSE: We performed a quality improvement initiative to monitor the change in protocol from purely intravenous therapy for perforated appendicitis to oral antibiotics at discharge once patients could tolerate eating. METHODS: Standardized prospective data were gathered on all children with perforated appendicitis treated under the new oral protocol from January 1 to December 31, 2014. Retrospective data through chart review were gathered on all children treated for perforated appendicitis during 2013. We compared demographics, clinical parameters, and hospital charges. RESULTS: Comparing 115 patients in 2013 and 144 in 2014, demographics and clinical characteristics were similar. In 2014, 95% of patients were discharged on oral therapy. Compared to the intravenous group, the enteric group had statistically lower rates of repeat ultrasound imaging (49.6% vs 35.1%) and PICC placement (98.3% vs 9.1%) and similar rates of intraabdominal abscess (20.9% vs 16.0%) and antibiotic change (26.1% vs 22.2%). In 2014, 55% of patients were discharged by postoperative day 5, compared to 33% in 2013. Total antibiotic days and readmission rate were similar, while hospital charges decreased by half. CONCLUSION: Our results reaffirm that transition to oral antibiotics is safe, effective, and cost efficient in treatment of perforated appendicitis in the child. PMID- 26996594 TI - Long-term results for Stage IIIB cervical cancer patients receiving external beam radiotherapy combined with either HDR (252)Cf or HDR (60)Co intracavitary brachytherapy. AB - PURPOSE: The aim of this work was to compare the long-term curative effects and complications of patients diagnosed with cervical cancer International Federation of Gynecology and Obstetrics IIIB (n = 430) as treated with Californium-252 ((252)Cf) or cobalt-60 ((60)Co) intracavitary brachytherapy (ICBT) combined with external beam radiotherapy (EBRT). METHODS AND MATERIALS: Cervical cancer cases with a history of treatment with (252)Cf or (60)Co ICBT combined with EBRT were selected from the Lithuanian National Cancer Institute database. Complications and second primary malignancies were compared in both patients groups. Estimates of the 5-, 10-, and 15-year overall survival and disease-free survival rates were computed with the Kaplan-Meier method and a Cox proportional hazards model applied using STATA software. RESULTS: At 5, 10, and 15 years, the overall survival rates were 46.9%, 39.3%, and 34.6% for the (252)Cf group and 35.4%, 26.9%, and 22.5% for the (60)Co group (p = 0.004), respectively. The disease-free survival rates were 42.1%, 35.0%, and 31.0% for the (252)Cf group and 32.0%, 25.1%, and 21.4% for the (60)Co group (p = 0.009), respectively. Histopathologic type of adenocarcinoma increased the risk of death for the (252)Cf group (hazard ratio 3.62). Histopathologic tumor type (hazard ratio 7.48) and recurrence (hazard ratio 2.83) were factors that statistically and significantly influenced the patient prognosis for the (60)Co group. CONCLUSIONS: Applying (252)Cf ICBT with EBRT was effective for International Federation of Gynecology and Obstetrics IIIB cervical cancer patients. Moreover, long-term followup data demonstrated higher survival rates in patients treated with (252)Cf ICBT than (60)Co ICBT. Complications in patients treated with neutron ICBT were not more frequent or severe than those treated with (60)Co ICBT. PMID- 26996595 TI - Pulsed-dose-rate vs. high-dose-rate intracavitary radiotherapy for locally advanced carcinoma of cervix: A prospective randomized study. AB - PURPOSE: To compare late radiation toxicities in patients with carcinoma of cervix treated with pulsed-dose-rate (PDR) vs. high-dose-rate (HDR) intracavitary radiotherapy (ICRT). METHODS AND MATERIALS: Between July 2010 to April 2012, 37 patients with Stage IIB-IIIB (International Federation of Gynecology and Obstetrics 2009) squamous cell carcinoma of cervix were randomized to receive either HDR (7 Gy each in three fractions, repeated weekly) or PDR (70 cGy hourly pulses for 39 hours, total 27 Gy) ICRT after external beam radiotherapy. Late rectal and bladder toxicities were assessed using Radiation Therapy Oncology Group criteria, and vaginal toxicity was graded as per common terminology criteria for adverse events. Overall survival and disease-free survival were estimated using Kaplan-Meier method. RESULTS: Nineteen patients received HDR and 18 received PDR ICRT with median followup 34 and 29 months, respectively. In HDR vs. PDR arm, late rectal toxicities grade >=2 (16.7% vs. 21.1%, p = 1.000), grade >=3 (10.5% vs. 0%, p = 0.486), late bladder toxicities grade >=2 (10.5% vs. 0%, p = 0.486), and late vaginal toxicities grade >=2 (15.8% vs. 5.6%, p = 0.604) were not statistically different. For HDR and PDR ICRT groups, 4-year disease-free survival was 67.1% vs. 71.8% (p = 0.195) and overall survival was 77% vs. 75% (p = 0.322), respectively. CONCLUSION: In this small group of patients, there were fewer events in form of late radiation toxicities in PDR arm, although statistically not significant. Further studies are required to define role of PDR compared to HDR ICRT in cervical carcinoma. PMID- 26996593 TI - Towards vast libraries of scaffold-diverse, conformationally constrained oligomers. AB - There is great interest in the development of probe molecules and drug leads that would bind tightly and selectively to protein surfaces that are difficult to target with traditional molecules, such as those involved in protein-protein interactions. The currently available evidence suggests that this will require molecules that are larger and have quite different chemical properties than typical Lipinski-compliant molecules that target enzyme active sites. We describe here efforts to develop vast libraries of conformationally constrained oligomers as a potentially rich source of these molecules. PMID- 26996596 TI - A pepducin designed to modulate P2Y2R function interacts with FPR2 in human neutrophils and transfers ATP to an NADPH-oxidase-activating ligand through a receptor cross-talk mechanism. AB - Several G-protein-coupled receptors (GPCRs) can be activated or inhibited in a specific manner by membrane-permeable pepducins, which are short palmitoylated peptides with amino acid sequences identical to an intracellular domain of the receptor to be targeted. Unlike the endogenous P2Y2R agonist ATP, the P2Y2PalIC2 pepducin, which has an amino acid sequence corresponding to the second intracellular loop of the human ATP receptor (P2Y2R), activated the superoxide anion-generating NADPH-oxidase in neutrophils. In addition to having a direct effect on neutrophils, the P2Y2R pepducin converted naive neutrophils to a primed state, which secondarily responded to ATP by producing superoxide. A pepducin with a peptide identical to the third intracellular loop of P2Y2R (P2Y2PalIC3) exhibited the same basic functions as P2Y2PalIC2, whereas one with a peptide that was identical to the first intracellular loop (P2Y2PalIC1) lacked these functions. The responses induced in neutrophils by the P2Y2R pepducins were not inhibited by the P2Y2R antagonist AR-C118925, and the receptor desensitization profile suggested the involvement of FPR2 rather than P2Y2R. Accordingly, antagonists/inhibitors of FPR2 attenuated the activities of the P2Y2R pepducins, which also selectively activated FPR2-overexpressing cells. In summary, we show that pepducins supposed to target P2Y2R activate human neutrophils through FPR2. We also show that the P2Y2PalIC2 pepducin can convert ATP from a non-activating agent to a potent neutrophil NADPH-oxidase activator. The molecular basis of this phenomenon involves cross-talk between the receptor/ligand pairs of P2Y2R/ATP and FPR2/P2Y2-pepducin. PMID- 26996597 TI - Divergent lncRNAs Regulate Gene Expression and Lineage Differentiation in Pluripotent Cells. AB - Divergent lncRNAs that are transcribed in the opposite direction to nearby protein-coding genes comprise a significant proportion (~20%) of total lncRNAs in mammalian genomes. Through genome-wide analysis, we found that the distribution of this lncRNA class strongly correlates with essential developmental regulatory genes. In pluripotent cells, divergent lncRNAs regulate the transcription of nearby genes. As an example, the divergent lncRNA Evx1as promotes transcription of its neighbor gene, EVX1, and regulates mesendodermal differentiation. At a single-cell level, early broad expression of Evx1as is followed by a rapid, high level transcription of EVX1, supporting the idea that Evx1as plays an upstream role to facilitate EVX1 transcription. Mechanistically, Evx1as RNA binds to regulatory sites on chromatin, promotes an active chromatin state, and interacts with Mediator. Based on our analyses, we propose that the biological function of thousands of uncharacterized lncRNAs of this class may be inferred from the role of their neighboring adjacent genes. PMID- 26996598 TI - CD82/KAI1 Maintains the Dormancy of Long-Term Hematopoietic Stem Cells through Interaction with DARC-Expressing Macrophages. AB - Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we examine the role of CD82/KAI1 in niche-mediated LT-HSC maintenance. We found that CD82/KAI1 is expressed predominantly on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs). In Cd82(-/-) mice, LT-HSCs were selectively lost as they exited from quiescence and differentiated. Mechanistically, CD82-based TGF-beta1/Smad3 signaling leads to induction of CDK inhibitors and cell-cycle inhibition. The CD82 binding partner DARC/CD234 is expressed on macrophages and stabilizes CD82 on LT-HSCs, promoting their quiescence. When DARC(+) BM macrophages were ablated, the level of surface CD82 on LT-HSCs decreased, leading to cell-cycle entry, proliferation, and differentiation. A similar interaction appears to be relevant for human HSPCs. Thus, CD82 is a functional surface marker of LT-HSCs that maintains quiescence through interaction with DARC-expressing macrophages in the BM stem cell niche. PMID- 26996602 TI - Evaluation of the transfection efficacies of quaternary ammonium salts prepared from sophorolipids. AB - Five quaternary ammonium amphiphilic compounds were synthesized from sophorolipid 1. These compounds were formulated in aqueous media and some of them (5 and 6) produced well-defined supramolecular aggregates which were characterized by DLS and zeta measurements. Their capacity to transfect four different eukaryotic cell lines in vitro was assessed. To evaluate the influence of the carbohydrate head group from the sophorolipids on the transfection efficacies, their deglycosylated analogues were also synthesized and tested for gene delivery. For all the compounds, the use of DOPE as a helper lipid in a 1 : 1 molar ratio with the ammonium-based lipids was required to obtain homogeneous formulations. The transfection results indicate that quaternary ammonium-based sophorolipids proved to be more efficient pDNA carriers than their deglycosylated counterparts. Moreover, the presence of the carbohydrate head group clearly contributed to the good biocompatibility of these cationic lipids. These cationic sophorolipid derivatives thus offer good potential for the development of new vectors for gene delivery based on renewable resources. PMID- 26996599 TI - MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency. AB - The interconversion between naive and primed pluripotent states is accompanied by drastic epigenetic rearrangements. However, it is unclear whether intrinsic epigenetic events can drive reprogramming to naive pluripotency or if distinct chromatin states are instead simply a reflection of discrete pluripotent states. Here, we show that blocking histone H3K4 methyltransferase MLL1 activity with the small-molecule inhibitor MM-401 reprograms mouse epiblast stem cells (EpiSCs) to naive pluripotency. This reversion is highly efficient and synchronized, with more than 50% of treated EpiSCs exhibiting features of naive embryonic stem cells (ESCs) within 3 days. Reverted ESCs reactivate the silenced X chromosome and contribute to embryos following blastocyst injection, generating germline competent chimeras. Importantly, blocking MLL1 leads to global redistribution of H3K4me1 at enhancers and represses lineage determinant factors and EpiSC markers, which indirectly regulate ESC transcription circuitry. These findings show that discrete perturbation of H3K4 methylation is sufficient to drive reprogramming to naive pluripotency. PMID- 26996600 TI - Nonepileptic seizures: an updated review. AB - Psychogenic nonepileptic seizures (PNES) are a functional neurological disorder/conversion disorder subtype, which are neurobehavioral conditions at the interface of neurology and psychiatry. Significant advancements over the past decade have been made in the diagnosis, management, and neurobiological understanding of PNES. This article reviews published PNES research focusing on semiologic features that distinguish PNES from epileptic seizures, consensus diagnostic criteria, the intersection of PNES and other comorbidities, neurobiological studies, evidence-based treatment interventions, and outcome studies. Epidemiology and healthcare utilization studies highlight a continued unmet medical need in the comprehensive care of PNES. Consensus guidelines for diagnostic certainty are based on clinical history, semiology of witnessed typical event(s), and EEG findings. While certain semiologic features may aid in the diagnosis of PNES, the gold standard remains capturing a typical event on video electroencephalography (EEG) showing the absence of epileptiform activity with history and semiology consistent with PNES. Medical-neurologic and psychiatric comorbidities are prevalent in PNES; these should be assessed in diagnostic evaluations and integrated into treatment interventions and prognostic considerations. Several studies, including a pilot, multicenter, randomized clinical trial, have now demonstrated that a cognitive behavioral therapy informed psychotherapy is an efficacious treatment for PNES, and additional efforts are necessary to evaluate the utility of pharmacologic and other psychotherapy treatments. Neuroimaging studies, while requiring replication, suggest that PNES may occur in the context of alterations within and across sensorimotor, emotion regulation/processing, cognitive control, and multimodal integration brain systems. Future research could investigate similarities and differences between PNES and other somatic symptom disorders. PMID- 26996603 TI - Collaboration between primitive cell membranes and soluble catalysts. AB - One widely held model of early life suggests primitive cells consisted of simple RNA-based catalysts within lipid compartments. One possible selective advantage conferred by an encapsulated catalyst is stabilization of the compartment, resulting from catalyst-promoted synthesis of key membrane components. Here we show model protocell vesicles containing an encapsulated enzyme that promotes the synthesis of simple fatty acid derivatives become stabilized to Mg(2+), which is required for ribozyme activity and RNA synthesis. Thus, protocells capable of such catalytic transformations would have enjoyed a selective advantage over other protocells in high Mg(2+) environments. The synthetic transformation requires both the catalyst and vesicles that solubilize the water-insoluble precursor lipid. We suggest that similar modified lipids could have played a key role in early life, and that primitive lipid membranes and encapsulated catalysts, such as ribozymes, may have acted in conjunction with each other, enabling otherwise-impossible chemical transformations within primordial cells. PMID- 26996604 TI - Connectivity matters - ultrafast isomerization dynamics of bisazobenzene photoswitches. AB - We have investigated the ultrafast dynamics of o-, m- and p-bisazobenzenes, which represent elementary building blocks for photoswitchable multiazobenzene nanostructures. The connectivity pattern within bisazobenzenes and the ensuing complex interactions between the individual azobenzene units determines the ultrafast dynamics of these compounds and their photochemical properties. While retaining a relatively high E -> Z isomerization quantum yield, o-bisazobenzene exhibits a very high thermal relaxation rate (half-life of 1.6 ms). Our theoretical calculations reveal that the geometry allows intramolecular excitonic interaction between the azobenzene units, which is reflected in the femtosecond transient absorption data via the simultaneous bleaching of the two excitonic bands. In contrast, the properties of m-bisazobenzene are very similar to the monomeric azobenzene, with the two units acting nearly independently from each other. The highest degree of pi conjugation extending over the two azobenzene units was observed for p-bisazobenzene, which results in strong planarity of the molecule, reduced excited state lifetime and relatively low isomerization quantum yield. Multiphotochromic systems bridge the gap between molecular photoswitches and macroscopic function and thus, understanding the properties of bisazobenzenes opens the way to the design and development of new structures with extensive and versatile applications. PMID- 26996601 TI - Limbic Activity Modulation Guided by Functional Magnetic Resonance Imaging Inspired Electroencephalography Improves Implicit Emotion Regulation. AB - The amygdala has a pivotal role in processing traumatic stress; hence, gaining control over its activity could facilitate adaptive mechanism and recovery. To date, amygdala volitional regulation could be obtained only via real-time functional magnetic resonance imaging (fMRI), a highly inaccessible procedure. The current article presents high-impact neurobehavioral implications of a novel imaging approach that enables bedside monitoring of amygdala activity using fMRI inspired electroencephalography (EEG), hereafter termed amygdala-electrical fingerprint (amyg-EFP). Simultaneous EEG/fMRI indicated that the amyg-EFP reliably predicts amygdala-blood oxygen level-dependent activity. Implementing the amyg-EFP in neurofeedback demonstrated that learned downregulation of the amyg-EFP facilitated volitional downregulation of amygdala-blood oxygen level dependent activity via real-time fMRI and manifested as reduced amygdala reactivity to visual stimuli. Behavioral evidence further emphasized the therapeutic potential of this approach by showing improved implicit emotion regulation following amyg-EFP neurofeedback. Additional EFP models denoting different brain regions could provide a library of localized activity for low cost and highly accessible brain-based diagnosis and treatment. PMID- 26996605 TI - Exciton localization in solution-processed organolead trihalide perovskites. AB - Organolead trihalide perovskites have attracted great attention due to the stunning advances in both photovoltaic and light-emitting devices. However, the photophysical properties, especially the recombination dynamics of photogenerated carriers, of this class of materials are controversial. Here we report that under an excitation level close to the working regime of solar cells, the recombination of photogenerated carriers in solution-processed methylammonium-lead-halide films is dominated by excitons weakly localized in band tail states. This scenario is evidenced by experiments of spectral-dependent luminescence decay, excitation density-dependent luminescence and frequency-dependent terahertz photoconductivity. The exciton localization effect is found to be general for several solution-processed hybrid perovskite films prepared by different methods. Our results provide insights into the charge transport and recombination mechanism in perovskite films and help to unravel their potential for high performance optoelectronic devices. PMID- 26996607 TI - How we manage variceal hemorrhage in cirrhotic patients. Key practical messages from the British Guidelines. AB - Variceal bleeding is a serious complication of portal hypertension with high morbidity and mortality. Advances in our understanding of screening and risk stratification along with evidence-based management strategies for acute variceal bleeding as well as primary and secondary prevention have improved overall outcomes in patients with portal hypertension. The guidelines recently published by the British Society of Gastroenterology (BSG) and Baveno 6 consensus have aimed to enhance the standard of care in the management of varices and their complications. This concise review focuses on the key practical messages for screening and management of varices and variceal bleeding in light of these guidelines. The review also takes into account important evidence published since the BSG guidelines and Baveno 6 consensus. PMID- 26996606 TI - Lighting Up Clostridium Difficile: Reporting Gene Expression Using Fluorescent Lov Domains. AB - The uses of fluorescent reporters derived from green fluorescent protein have proved invaluable for the visualisation of biological processes in bacteria grown under aerobic conditions. However, their requirement for oxygen has limited their application in obligate anaerobes such as Clostridium difficile. Fluorescent proteins derived from Light, Oxygen or Voltage sensing (LOV) domains have been shown to bridge this limitation, but their utility as translational fusions to monitor protein expression and localisation in a strict anaerobic bacterium has not been reported. Here we demonstrate the utility of phiLOV in three species of Clostridium and its application as a marker of real-time protein translation and dynamics through genetic fusion with the cell division protein, FtsZ. Time lapse microscopy of dividing cells suggests that Z ring assembly arises through the extension of the FtsZ arc starting from one point on the circumference. Furthermore, through incorporation of phiLOV into the flagella subunit, FliC, we show the potential of bacterial LOV-based fusion proteins to be successfully exported to the extracellular environment. PMID- 26996608 TI - Thermally Driven Photonic Actuator Based on Silica Opal Photonic Crystal with Liquid Crystal Elastomer. AB - We have developed a novel thermoresponsive photonic actuator based on three dimensional SiO2 opal photonic crystals (PCs) together with liquid crystal elastomers (LCEs). In the process of fabrication of such a photonic actuator, the LCE precursor is infiltrated into the SiO2 opal PC followed by UV light-induced photopolymerization, thereby forming the SiO2 opal PC/LCE composite film with a bilayer structure. We find that this bilayer composite film simultaneously exhibits actuation behavior as well as the photonic band gap (PBG) response to external temperature variation. When the SiO2 opal PC/LCE composite film is heated, it exhibits a considerable bending deformation, and its PBG shifts to a shorter wavelength at the same time. In addition, this actuation is quite fast, reversible, and highly repeatable. The thermoresponsive behavior of the SiO2 opal PC/LCE composite films mainly derives from the thermal-driven change of nematic order of the LCE layer which leads to the asymmetric shrinkage/expansion of the bilayer structure. These results will be of interest in designing optical actuator systems for environment-temperature detection. PMID- 26996609 TI - A study of the impact of co-adsorbents on DSSC electron transfer processes: anti pi-stacking vs. shield effect. AB - In this study we report a detailed exploration of the use of two different co adsorbents - namely bis-methoxyphenylphosphinic acid (BMPP) and chenodeoxycholic acid (CDCA) - known to increase photoconversion efficiency (PCE) of DSSCs sensitized with N719. We have explored the variation of their abilities with the [co-ads]/[D] ratio of the sensitization bath in order to lower the intermolecular deactivations (anti-pi-stacking effect) and recombinations between photo-injected electrons and the oxidized mediator (shield effect). EIS-lambda technique has been used for this purpose, allowing the two effects considered here to be accurately quantified. DSSC containing BMPP allowed to improve the cell PCE by 60% with a ratio [co-ads]/[D] = 1, exhibiting a strong shield effect, while the maximum PCE obtained with CDCA was slightly over 7% (corresponding to 30% improvement) with a ratio [co-ads]/[D] = 10 and exhibiting a strong anti-pi stacking effect. PMID- 26996611 TI - Photoswitching of an intramolecular chiral stack in a helical tetrathiazole. AB - On-off photoswitching of circularly polarized luminescence was achieved using a pyrene-bearing helical tetrathiazole, in which two pyrene fluorophores stack in a chiral fashion (folded state). The pyrene-excimer based CPL was reversibly controlled by a geometrical change of the tetrathiazole upon photoisomerization. PMID- 26996610 TI - A p-i-n junction diode based on locally doped carbon nanotube network. AB - A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~10(4)), large forward current (~12.2 MUA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 MUm. PMID- 26996612 TI - Identification of genes for controlling swine adipose deposition by integrating transcriptome, whole-genome resequencing, and quantitative trait loci data. AB - Backfat thickness is strongly associated with meat quality, fattening efficiency, reproductive performance, and immunity in pigs. Fat storage and fatty acid synthesis mainly occur in adipose tissue. Therefore, we used a high-throughput massively parallel sequencing approach to identify transcriptomes in adipose tissue, and whole-genome differences from three full-sibling pairs of pigs with opposite (high and low) backfat thickness phenotypes. We obtained an average of 38.69 million reads for six samples, 78.68% of which were annotated in the reference genome. Eighty-nine overlapping differentially expressed genes were identified among the three pair comparisons. Whole-genome resequencing also detected multiple genetic variations between the pools of DNA from the two groups. Compared with the animal quantitative trait loci (QTL) database, 20 differentially expressed genes were matched to the QTLs associated with fatness in pigs. Our technique of integrating transcriptome, whole-genome resequencing, and QTL database information provided a rich source of important differentially expressed genes and variations. Associate analysis between selected SNPs and backfat thickness revealed that two SNPs and one haplotype of ME1 significantly affected fat deposition in pigs. Moreover, genetic analysis confirmed that variations in the differentially expressed genes may affect fat deposition. PMID- 26996613 TI - Metabolic Burden: Cornerstones in Synthetic Biology and Metabolic Engineering Applications. AB - Engineering cell metabolism for bioproduction not only consumes building blocks and energy molecules (e.g., ATP) but also triggers energetic inefficiency inside the cell. The metabolic burdens on microbial workhorses lead to undesirable physiological changes, placing hidden constraints on host productivity. We discuss cell physiological responses to metabolic burdens, as well as strategies to identify and resolve the carbon and energy burden problems, including metabolic balancing, enhancing respiration, dynamic regulatory systems, chromosomal engineering, decoupling cell growth with production phases, and co utilization of nutrient resources. To design robust strains with high chances of success in industrial settings, novel genome-scale models (GSMs), (13)C-metabolic flux analysis (MFA), and machine-learning approaches are needed for weighting, standardizing, and predicting metabolic costs. PMID- 26996614 TI - Protein Formulations for Emulsions and Solid-in-Oil Dispersions. AB - Needs from medical and cosmetic areas have led to the design of novel nanosized emulsions and solid-in-oil dispersions of proteins. Here, we describe the production of those emulsions and dispersions using high-energy methodologies such as high-pressure homogenization or ultrasound. Recent work has resulted in new mechanistic insights related to the formation of protein emulsions and dispersions. The production method and composition of these formulations can determine major parameters such as size, stability, and functionality, and therefore their final application. Aqueous nanoemulsions of proteins can be used for drug delivery, while solid-in-oil dispersions are often used in transdermal applications. PMID- 26996615 TI - Characterizing Protein-Protein Interactions Using Mass Spectrometry: Challenges and Opportunities. AB - During the past decades, mass spectrometry (MS)-based proteomics has become an important technology to identify protein-protein interactions (PPIs). The application of a quantitative filter in protein enrichments from crude lysates to discriminate bona fide interactors from background proteins has proved to be particularly powerful. Recently, many different approaches to identify PPIs have been developed, including proximity-ligation technology and global interactome profiling based on the co-behavior of protein complexes in biochemical purification or perturbation experiments. Furthermore, methodologies have been introduced that provide information regarding the stoichiometry and topology of detected PPIs. We review these novel methodologies and emphasize the need to miniaturize workflows to analyze protein interactions in biological and pathological contexts where sample amounts are limited. PMID- 26996616 TI - Fluparoxan: A Comprehensive Review of its Discovery, Adrenergic and CNS Activity and Treatment of Cognitive Dysfunction in Central Neurodegenerative Diseases. AB - BACKGROUND: The design, medicinal chemistry, pharmacokinetics and development of the highly selective alpha2-adrenoceptor antagonist fluparoxan are reviewed. METHOD: The drug's activity and selectivity in vitro, its efficacy in animals and its excellent oral pharmacokinetics and central alpha2-adrenoceptor antagonist activity in man, are evaluated as well as its ability to increase extracellular levels of noradrenaline, dopamine and acetylcholine in vivo. CONCLUSION: Furthermore, its potential for the treatment of central neurodegenerative diseases is highlighted, in particular its improvement of cognitive dysfunction in schizophrenia and in models of Alzheimer's disease. PMID- 26996617 TI - Review on EGFR Inhibitors: Critical Updates. AB - Epidermal Growth Factor Receptor (EGFR) is a transmembrane glycoprotein that constitutes one of the four members of ErbB family of tyrosine kinase receptors. Activation of EGFR leads to autophosphorylation of receptor tyrosine kinase that initiates a cascade of downstream signaling pathways involved in regulating cellular proliferation, differentiation, and survival. EGFR is abnormally activated by various mechanisms like receptor overexpression, mutation, ligand dependent receptor dimerization, ligand-independent activation and is associated with the development of variety of human cancers. EGFR inhibition is one of the key targets for cancer chemotherapy. Approval of tyrosine kinase inhibitors such as erlotinib, gefitinib, and lapatinib for the treatment of non-small cell lung cancer led to tremendous development of novel EGFR inhibitors in the last decade. Diverse class of chemical compounds from the synthetic origin has been extensively studied. This review highlights the various classes of synthetically derived molecules which have been reported in the last few years as potential EGFR and EGFR/ErbB-2 dual inhibitors. A brief synthetic methodology to access these compounds has been highlighted along with the SAR. We strongly believe that this review will provide a platform to the synthetic chemists and biologists to design and synthesize new and potent compounds that inhibit EGFR and ErbB-2. PMID- 26996618 TI - G4 Aptamers: Trends in Structural Design. AB - Many potent DNA aptamers are known to contain a G-quadruplex (G4) core. Structures and applications of the majority of such aptamers have been reviewed previously. The present review focuses on the design and optimization of G4 aptamers. General features of bioactive G4s are analyzed, and the main strategies for construction of aptamers with desired properties and topologies, including modular assembly, control of an aptamer folding and some others, are outlined. Chemical modification as a method for post-SELEX G4 aptamer optimization is also discussed, and the effects of loop and core modifications are compared. Particular attention is paid to the emerging trends, such as the development of genomic G4- inspired aptamers and the combinatorial approaches which aim to find a balance between rational design and selection. PMID- 26996619 TI - The Chemistry of Galanthamine. Classical Synthetic Methods and Comprehensive Study on its Analogues. AB - Galanthamine as an Amaryllidaceae alkaloid has an important role in the treatment of Alzheimer's disease. Some efforts were made to elaborate the total synthesis, and hundreds of its derivatives were prepared to find a more effective molecule with advantageous properties. Moreover, almost every part of the tetracycle was changed; in members of the rings, in the nature and position of the heteroatoms, and ring-opened analogues were also synthesized. In this review the basic synthetic works and the most important derivatives and analogues are overviewed. PMID- 26996620 TI - Titanium Dioxide Nanoparticles: a Risk for Human Health? AB - Titanium dioxide (TiO2) is a natural oxide of the element titanium with low toxicity, and negligible biological effects. The classification as bio-inert material has given the possibility to normal-sized (>100 nm) titanium dioxide particles (TiO2-NPs) to be extensively used in food products and as ingredients in a wide range of pharmaceutical products and cosmetics, such as sunscreens and toothpastes. Therefore, human exposure may occur through ingestion and dermal penetration, or through inhalation route, during both the manufacturing process and use. In spite of the extensively use of TiO2-NPs, the biological effects and the cellular response mechanisms are still not completely elucidated and thus a deep understanding of the toxicological profile of this compound is required. The main mechanism underlining the toxicity potentially triggered by TiO2-NPs seems to involve the reactive oxygen species (ROS) production, resulting in oxidative stress, inflammation, genotoxicity, metabolic change and potentially carcinogenesis. The extent and type of cell damage strongly depend on chemical and physical characteristics of TiO2-NPs, including size, crystal structure and photo-activation. In this mini-review, we would like to discuss the latest findings on the adverse effects and on potential human health risks induced by TiO2-NPs exposure. PMID- 26996621 TI - Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain. AB - In complementary medicine, aromatherapy uses essential oils to improve agitation and aggression observed in dementia, mood, depression, anxiety and chronic pain. Preclinical research studies have reported that the essential oil obtained from bergamot (BEO) fruit (Citrus bergamia, Risso) modifies normal and pathological synaptic plasticity implicated, for instance, in nociceptive and neuropathic pain. Interestingly, recent results indicated that BEO modulates sensitive perception of pain in different models of nociceptive, inflammatory and neuropathic pain modulating endogenous systems. Thus, local administration of BEO inhibited the nociceptive behavioral effect induced by intraplantar injection of capsaicin or formalin in mice. Similar effects were observed with linalool and linalyl acetate, major volatile components of the phytocomplex, Pharmacological studies showed that the latter effects are reversed by local or systemic pretreatment with the opioid antagonist naloxone hydrochloride alike with naloxone methiodide, high affinity peripheral MU-opioid receptor antagonist. These results and the synergistic effect observed following systemic or intrathecal injection of an inactive dose of morphine with BEO or linalool indicated an activation of peripheral opioid system. Recently, in neuropathic pain models systemic or local administration of BEO or linalool induced antiallodynic effects. In particular, in partial sciatic nerve ligation (PSNL) model, intraplantar injection of the phytocomplex or linalool in the ipsilateral hindpaw, but not in the contralateral, reduced PSNL-induced extracellularsignal- regulated kinase (ERK) activation and mechanical allodynia. In neuropathic pain high doses of morphine are needed to reduce pain. Interestingly, combination of inactive doses of BEO or linalool with a low dose of morphine induced antiallodynic effects in mice. Peripheral cannabinoid and opioid systems appear to be involved in the antinociception produced by intraplantar injection of beta caryophyllene, present in different essential oils including BEO. The data gathered so far indicate that the essential oil of bergamot is endowed with antinociceptive and antiallodynic effects and contribute to form the rational basis for rigorous testing of its efficacy in complementary medicine. PMID- 26996622 TI - Mesoporous Silica Nanoparticles in Cancer Therapy: Relevance of the Targeting Function. AB - In the last years, the oncologic research is focusing on the optimization of the clinical approach to the tumor disease, through the development of new therapeutic strategies combining currently used antineoplastic drugs to targeted delivery systems. In fact, due to the drugs poor selectivity for cancer cells, an highly aggressive style of dosing is necessary to eradicate tumors, causing severe toxicity to normal cells. Therefore, localized drug delivery would, ideally, improve the therapeutic efficacy, minimizing side effects. Mesoporous silica nanoparticles (MSNs) have been proposed as a promising class of versatile drug/DNA delivery vehicles, as well as efficient tools for fluorescent cell tracking. To date, the major limitation is that MSNs enter the cells regardless of a target-specific functionalization. Therefore, this review is aimed to give a brief up to date overview on mesoporous silica based-drug delivery vehicles, specifically applied to tumor therapy, giving particular emphasis to the importance of a targeting function grafted on the carrier surface, so to avoid an indiscriminate uptake by cells. PMID- 26996623 TI - Resveratrol and Its Analogs As Antitumoral Agents For Breast Cancer Treatment. AB - Resveratrol (3,5,4'-tri-hydroxystilbene) (RSV), a naturally occurring phytoalexin, readily available in the diet, has gained interest as a non-toxic agent capable of displaying cancer-preventing and anti-cancer properties. Several studies, using both in vitro and in vivo models, have illustrated RSV capacity to modulate a multitude of signaling pathways associated with cellular growth and division, apoptosis, angiogenesis, invasion and metastasis. However, its clinical application is limited because of a low oral bioavailability with high adsorption but rapid metabolism and low tissue concentrations. Several chemical modifications to the backbone structure have been made for the purpose of improving pharmacokinetic parameters. One promising strategy involves the introduction of methoxylic or hydroxylic groups on the phenylic rings of RSV. Moreover, by replacing the alkene linker between the two aromatic rings with a heterocyclic system rigid analogs such as 2,3- thiazolidin-4-ones and 3-chloro azetidin-2-ones that displayed higher cytotoxic activity and hence higher ability to inhibit in vitro breast cancer cell growth have been synthesized. In vitro studies have demonstrated, for some of these compounds, a greater bioaccessibility than RSV and more selective inhibitory effects on breast cancer cell growth. Further investigations, particularly in vivo, are required as next step to implicate these analogs as pharmacologic agents for a possible clinical anticancer application. PMID- 26996624 TI - Phosphorylation Processes Controlling Aromatase Activity in Br east Cancer: An Update. AB - Local estrogen production from aromatase-mediated conversion of androgens is an important mechanism of autocrine growth stimulation in hormone-dependent breast cancers. The control mechanism of aromatase enzymatic activity in recent years has been demonstrated to be more complex than previously identified. Indeed, it is well known that aromatase expression is regulated at the transcriptional level through the alternative use of tissue-specific promoters, whereas it has become clear that the activity of this enzyme is also controlled by post-transcriptional modifications, such as phosphorylation processes. This paper presents a selective review of the novel findings in this area showing phosphorylation/dephosphorylation of aromatase as a switch to rapidly modulate its enzymatic activity. Particularly, we describe studies conducted in our laboratories, focusing on the role of estrogens in modulating aromatase activity in estrogen-dependent breast cancer cells. Two separate mechanisms are described. First, 17beta-estradiol (E2), through c-Src kinase, is able to enhance tyrosine phosphorylation levels of aromatase protein and increases its enzymatic activity and estrogen biosynthesis. Secondly, E2, through the activation of PI3K/Akt pathway, impairs the ability of the tyrosine phosphatase PTP1B to dephosphorylate aromatase, resulting in a consequent enhanced phosphorylation and activity of the aromatase protein itself. These new controls of aromatase function provide insights into the mechanisms through which local estrogen production can be altered in breast cancer tissues. They also offer a vast array of possibilities for identifying different cell signalings that should be targeted in novel therapeutic strategies for breast cancer treatment. PMID- 26996625 TI - Caspase-1-independent Maturation of IL-1beta in Ischemic Brain Injury: is there a Role for Gelatinases? AB - Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain. Interleukin (IL)-1beta is a pro-inflammatory cytokine that plays a pivotal role in the detrimental inflammatory processes that participate to cerebral ischemic damage. After injury, it is produced by distinct cells of the neurovascular unit as an inactive precursor, pro-IL-1beta. Although previous studies have suggested that caspase-1 is the main enzyme implicated in the cleavage of pro-IL-1beta into the biologically active cytokine, recent work has demonstrated that, under ischemia-reperfusion conditions, other mechanisms may be involved in cytokine maturation. Indeed, we have shown that in rats subjected to transient middle cerebral artery occlusion (MCAo), elevation of IL-1beta levels is paralleled by an elevation of gelatinolytic, but not caspase-1 activity in the injured hemisphere and pharmacological inhibition of gelatinases, i.e. matrix metalloproteases (MMP)-2 and MMP-9 prevents cytokine maturation. These findings further support the hypothesis that, under ischemia-reperfusion injury, cerebral elevation of IL-1beta occurs via mechanisms other than caspase-1, likely involving gelatinases. PMID- 26996626 TI - Improved functionality of fermented milk is mediated by the synbiotic interaction between Cudrania tricuspidata leaf extract and Lactobacillus gasseri strains. AB - This study was designed to investigate the cooperative effect of selected Lactobacillus gasseri strains and Cudrania tricuspidata (CT) leaf extract in enhancing the health-promoting activities of fermented milk. Addition of CT increased total bacterial counts and proteolysis during fermentation of milk with L. gasseri strains. Antioxidant capacities were determined by measuring the ABTS, DPPH, and peroxyl radical scavenging activities and ferric reducing power. The antioxidant capacity of CT-supplemented milk was greater than that of milk without supplementation; moreover, the antioxidant activity of CT-supplemented milk was synergistically improved by fermentation with L. gasseri strains. In particular, CT-supplemented milk fermented by L. gasseri 505 showed the highest antioxidant activity. The phenolic compounds in CT, such as neo-chlorogenic, chlorogenic, and caffeic acid, were metabolized during fermentation with L. gasseri strains, and 3,4-dihydroxy-hydrocinnamic acid was produced as a fermentation metabolite. Moreover, the liberation of bioactive peptides of fermented milk was increased by the proteolytic activity of L. gasseri strains. In particular, six peptides, which were mainly derived from beta-casein, were newly identified in this study. These findings suggest that L. gasseri strains metabolize the phenolic acids in the CT and the bioactive peptides released through this interaction improve the antioxidant activity of the fermented milk. PMID- 26996627 TI - SpiE interacts with Corynebacterium glutamicum WhcE and is involved in heat and oxidative stress responses. AB - The gene whcE in Corynebacterium glutamicum positively responds to oxidative and heat stress. To search for proteins that interact with WhcE, we employed a two hybrid system with WhcE as the bait. Sequencing analysis of the isolated clones revealed peptide sequences, one of which showed high sequence identity to a hydrophobe/amphiphile efflux-1 family transporter encoded by NCgl1497. The interaction of the NCgl1497-encoded protein with WhcE in vivo was verified using reporter gene expression by real-time quantitative PCR (RT-qPCR). The WhcE protein strongly interacted with the NCgl1497-encoded protein in the presence of oxidative and heat stress. Furthermore, purified WhcE and NCgl1497-encoded proteins interacted in vitro, especially in the presence of the oxidant diamide, and the protein-protein interaction was disrupted in the presence of the reductant dithiothreitol. In addition, the transcription of NCgl1497 was activated approximately twofold in diamide- or heat-treated cells. To elucidate the function of the NCgl497 gene, an NCgl1497-deleted mutant strain was constructed. The mutant showed decreased viability in the presence of diamide and heat stress. The mutant strain also exhibited reduced transcription of the thioredoxin reductase gene, which is known to be regulated by whcE. Based on the results, NCgl1497 was named spiE (stress protein interacting with WhcE). Collectively, our data suggest that spiE is involved in the whcE-mediated oxidative stress response pathway of C. glutamicum. PMID- 26996629 TI - Effect of Glycine on Adipocyte Hypertrophy in a Metabolic Syndrome Rat Model. AB - Glycine (Gly) lowers hypercholesterolemia, hypertriglyceridemia and hypertension but its role in preventing adipocyte hypertrophy and modulating enzymatic activity of adipocytes has not been studied. Here we evaluate the effect of 1% Gly in the diet on adipocyte hypertrophy and the modulation of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) in a metabolic syndrome (MS) rat model with intra-abdominal obesity. 32 Wistar rats were divided into 3 groups: control (C), MS, MS plus Gly (MS+Gly), and MS+Gly plus strychnine (MS+Gly+S). MS was induced by administering 30% sucrose in the drinking water for 16 weeks. In the MS+Gly and MS+Gly+S groups, the sucrose solution plus 1% Gly and 1 % Gly plus strychnine 10 MUM were given during the last 4 weeks of the sucrose treatment. After 16 weeks of treatment, rats were sacrificed and the adipose tissue dissected. Gly in MS rats decreased body weight, intra-abdominal adipose tissue, adipocyte hypertrophy, blood pressure, triglycerides, insulin, HOMA-IR index, leptin, total fatty acids, non-esterified fatty acids and LPL activity. It increased fatty acids of the phospholipids, perilipin A expression and it decreased HSL expression, without changing LPL expression. The Gly receptor subunit-beta was identified in adipocytes. In conclusion, Gly treatment regulates the activity of enzymes involved in the lipid metabolism of the adipocytes through the Gly receptor and it decreases the effects of the high sucrose diet. PMID- 26996628 TI - Characterization of bifunctional L-glutathione synthetases from Actinobacillus pleuropneumoniae and Actinobacillus succinogenes for efficient glutathione biosynthesis. AB - Glutathione (GSH), an important bioactive substance, is widely applied in pharmaceutical and food industries. In this work, two bifunctional L-glutathione synthetases (GshF) from Actinobacillus pleuropneumoniae (GshFAp) and Actinobacillus succinogenes (GshFAs) were successfully expressed in Escherichia coli BL-21(DE3). Similar to the GshF from Streptococcus thermophilus (GshFSt), GshFAp and GshFAs can be applied for high titer GSH production because they are less sensitive to end-product inhibition (Ki values 33 and 43 mM, respectively). The active catalytic forms of GshFAs and GshFAp are dimers, consistent with those of GshFPm (GshF from Pasteurella multocida) and GshFSa (GshF from Streptococcus agalactiae), but are different from GshFSt (GshF from S. thermophilus) which is an active monomer. The analysis of the protein sequences and three dimensional structures of GshFs suggested that the binding sites of GshFs for substrates, L cysteine, L-glutamate, gamma-glutamylcysteine, adenosine-triphosphate, and glycine are highly conserved with only very few differences. With sufficient supply of the precursors, the recombinant strains BL-21(DE3)/pET28a-gshFas and BL 21(DE3)/pET28a-gshFap were able to produce 36.6 and 34.1 mM GSH, with the molar yield of 0.92 and 0.85 mol/mol, respectively, based on the added L-cysteine. The results showed that GshFAp and GshFAs are potentially good candidates for industrial GSH production. PMID- 26996630 TI - Interface instability modes in freezing colloidal suspensions: revealed from onset of planar instability. AB - Freezing colloidal suspensions widely exists in nature and industry. Interface instability has attracted much attention for the understandings of the pattern formation in freezing colloidal suspensions. However, the interface instability modes, the origin of the ice banding or ice lamellae, are still unclear. In-situ experimental observation of the onset of interface instability remains absent up to now. Here, by directly imaging the initial transient stage of planar interface instability in directional freezing colloidal suspensions, we proposed three interface instability modes, Mullins-Sekerka instability, global split instability and local split instability. The intrinsic mechanism of the instability modes comes from the competition of the solute boundary layer and the particle boundary layer, which only can be revealed from the initial transient stage of planar instability in directional freezing. PMID- 26996631 TI - How I do it: modified Todd's meatoplasty. AB - BACKGROUND: Chronic otorrhoea after canal wall down mastoidectomy can be a clinical challenge. Basic principles for canal wall down surgery include establishing a large meatus. Several meatoplasty techniques have been reported. This paper describes this new indication for Todd's meatoplasty with surgical improvements. STUDY DESIGN: Retrospective review. SETTING: Academic tertiary referral centre. METHODS: Modifications of transposition postauricular flap meatoplasty are reported. This technique was applied in a series of patients with chronic otorrhoea after a canal wall down mastoidectomy. RESULTS: In general, a dry radical cavity was successfully created within six weeks and follow-up visits at the out-patient clinic were reduced. Only minor complications occurred, which are all reported. CONCLUSION: The postauricular flap meatoplasty is a valuable tool in the management of chronic otorrhoea after an open cavity approach for cholesteatoma. PMID- 26996632 TI - Behavioural effects of basal ganglia rho-kinase inhibition in the unilateral 6 hydroxydopamine rat model of Parkinson's disease. AB - Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects more than six million people in the world. While current available pharmacological therapies for PD in the early stages of the disease usually improve motor symptoms, they cause side effects, such as fluctuations and dyskinesias in the later stages. In this later stage, high frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option which is most successful to treat drug resistant advanced PD. It has previously been demonstrated that activation of Rho/Rho-kinase pathway is involved in the dopaminergic cell degeneration which is one of the main characteristics of PD pathology. In addition, the involvement of this pathway has been suggested in diverse cellular events in the central nervous system; such as epilepsy, anxiety related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However, up to date, to our knowledge there are no previous reports showing the beneficial effects of the potent Rho-kinase inhibitor Y-27632 in the 6-hydroxydopamine (6-OHDA) rat model of PD. Therefore, in the present study, we investigated the behavioural effects of basal ganglia Y-27632 microinjections in this PD model. Our results indicated that basal ganglia Y 27632 microinjections significantly decreased the number of contralateral rotations-induced by apomorphine, significantly increased line crossings in the open-field test, contralateral forelimb use in the limb-use asymmetry test and contralateral tape playing time in the somatosensory asymmetry test, which may suggest that Y-27632 could be a potentially active antiparkinsonian agent. PMID- 26996633 TI - Factors associated with inter-institutional variations in sepsis rates of very low-birth-weight infants in 34 Malaysian neonatal intensive care units. AB - INTRODUCTION: This study aimed to determine whether patient loads, infant status on admission and treatment interventions were significantly associated with inter institutional variations in sepsis rates in very-low-birth-weight (VLBW) infants in the Malaysian National Neonatal Registry (MNNR). METHODS: This was a retrospective study of 3,880 VLBW (<= 1,500 g) infants admitted to 34 neonatal intensive care units (NICUs) in the MNNR. Sepsis was diagnosed in symptomatic infants with positive blood culture. RESULTS: Sepsis developed in 623 (16.1%) infants; 61 (9.8%) had early-onset sepsis (EOS) and 562 (90.2%) had late-onset sepsis (LOS). The median EOS rate of all NICUs was 1.0% (interquartile range [IQR] 0%, 2.0%). Compared with NICUs reporting no EOS (n = 14), NICUs reporting EOS (n = 20) had significantly higher patient loads (total live births, admissions, VLBW infants, outborns); more mothers with a history of abortions, and antenatal steroids and intrapartum antibiotic use; more infants requiring resuscitation procedures at birth; higher rates of surfactant therapy, pneumonia and insertion of central venous catheters. The median LOS rate of all NICUs was 14.5% (IQR 7.8%, 19.2%). Compared with NICUs with LOS rates below the first quartile (n = 8), those above the third quartile (n = 8) used less intrapartum antibiotics, and had significantly bigger and more mature infants, more outborns, as well as a higher number of sick infants requiring ventilator support and total parenteral nutrition. CONCLUSION: Patient loads, resuscitation at birth, status of infants on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis. PMID- 26996634 TI - Evaluation of the effect of double reporting on test accuracy in screening and diagnostic imaging studies: A review of the evidence. AB - Diagnostic error in radiology is not uncommon, with rates of clinically significant error reported to be as high as 20%. Radiological errors are often multifactorial, however, perceptual factors are thought to be mainly responsible. One way of reducing perceptual error is that of double reporting, which refers to the interpretation of radiological investigations by two observers, with strategies of arbitration and consensus available to settle discordant reports. Independent double reporting, where observers have no knowledge of each other's reports, is generally considered to be the most effective form. The impact of double reporting on diagnostic efficacy has been primarily explored in screening mammography, where it has consistently been shown to improve sensitivity, cancer detection rate and depending on local policy, have a positive influence on recall rates. Subsequently, the adoption of double reporting is reported as standard practice in many national and regional breast cancer-screening programmes. To a lesser extent, the impact of double reporting has also been investigated for neuroradiology, thoracic and gastrointestinal imaging, with small-scale studies in these fields showing promising results. With the widespread implementation of digitisation and the ease of access to images, the efficacy and cost effectiveness of double reporting for other common radiological investigations requires attention. The review will evaluate the evidence regarding the effect of double interpretation of diagnostic imaging studies on test accuracy. PMID- 26996635 TI - Use of non-irradiated blood components in Campath (alemtuzumab)-treated renal transplant patients. AB - BACKGROUND: The prevention of transfusion-associated graft-versus-host disease (TA-GvHD) through the irradiation of components is key as there is no effective treatment. Universal leucodepletion reduces but may not eliminate TA-GvHD; therefore, irradiation is still recommended. In 2010, Campath (alemtuzumab) was added as an indication for irradiation but was not implemented everywhere. OBJECTIVES: To identify any cases of TA-GvHD in our Campath-conditioned renal transplant patients, who were transfused with non-irradiated components. METHODS: Retrospective study of Campath-conditioned renal transplant patients transfused with non-irradiated components. In those transfused up to 9 months following Campath who survived to 1-year follow-up, TA-GvHD was excluded. For patients not followed-up for a full year, we reviewed medical records for features of TA-GvHD. For patients transfused after 9 months following Campath, survival of at least 3 months following last transfusion excluded TA-GvHD. RESULTS: Six hundred and forty-seven Campath-conditioned renal transplant patients were transfused; 616 were transfused within 9 months following Campath; 601 were alive at 1 year, excluding TA-GvHD. Twelve died and three were not followed-up for a full year, but a review of medical records excluded TA-GvHD. The 31 patients transfused 9 months or longer following Campath were all alive 6 months following the last transfusion, excluding TA-GvHD. CONCLUSIONS: Despite receiving non-irradiated components, none of the 647 Campath-conditioned renal transplant patients developed TA-GvHD. Further reviews to replicate our data could enable change to guidance, at least in UK where components are leucodepleted, as an unnecessary requirement for irradiated components has both clinical delay and cost implications. PMID- 26996636 TI - Fundamental developments in infrared spectroscopic imaging for biomedical applications. AB - Infrared chemical imaging is a rapidly emerging field with new advances in instrumentation, data acquisition and data analysis. These developments have had significant impact in biomedical applications and numerous studies have now shown that this technology offers great promise for the improved diagnosis of the diseased state. Relying on purely biochemical signatures rather than contrast from exogenous dyes and stains, infrared chemical imaging has the potential to revolutionise histopathology for improved disease diagnosis. In this review we discuss the recent advances in infrared spectroscopic imaging specifically related to spectral histopathology (SHP) and consider the current state of the field. Finally we consider the practical application of SHP for disease diagnosis and consider potential barriers to clinical translation highlighting current directions and the future outlook. PMID- 26996639 TI - Looking to the future: Framing the implementation of interprofessional education and practice with scenario planning. AB - BACKGROUND: Adapting to interprofessional education and practice requires a change of perspective for many health professionals. We aimed to explore the potential of scenario planning to bridge the understanding gap and framing strategic planning for interprofessional education (IPE) and practice (IPP), as well as to implement innovative techniques and technology for large-group scenario planning. METHODS: A full-day scenario planning workshop incorporating innovative methodology was designed and offered to participants. The 71 participants included academics from nine universities, as well as service providers, government, students and consumer organisations. The outcomes were evaluated by statistical and thematic analysis of a mixed method survey questionnaire. RESULTS: The scenario planning method resulted in a positive response as a means of collaboratively exploring current knowledge and broadening entrenched attitudes. It was perceived to be an effective instrument for framing strategy for the implementation of IPE/IPP, with 81 percent of respondents to a post-workshop survey indicating they would consider using scenario planning in their own organisations. DISCUSSION: The scenario planning method can be used by tertiary academic institutions as a strategy in developing, implementing and embedding IPE, and for the enculturation of IPP in practice settings. PMID- 26996640 TI - Laying the groundwork for Tobacco Cessation Education in Medical Colleges in Indonesia. AB - BACKGROUND: This paper describes a pioneering effort to introduce smoking cessation into Indonesia's medical school curriculum, and the first ever attempt to fully integrate tobacco control in all four years of medical school anywhere in Southeast Asia. The development, pretesting, and piloting of an innovative modular tobacco curriculum are discussed as well as the challenges that face implementation. METHODS: In-depth interviews were conducted with medical school administrators and faculty in four medical colleges to determine interest in and willingness to fully integrate tobacco cessation into the college curriculum. A tobacco focused curriculum review, student focus groups, and a survey of medical students (n = 579) assessed current exposure to information about tobacco and interest in learning cessation skills. A modular tobacco curriculum was developed and was pretested, modified, piloted, and evaluated. Qualitative research was conducted to identify potential challenges to future curriculum implementation. RESULTS: Fifteen modules were successfully developed focusing on the relationship between tobacco and specific organ systems, diseases related to smoking, the impact of tobacco on medication effectiveness, and information on how to explain to patients about effects of tobacco on their health condition. Lecturers and students positively evaluated the curriculum as increasing their competency to support cessation during illness as a teachable moment. Systemic challenges to implementing the curriculum were identified including shifts in pedagogy, decentralized curriculum decision-making, and frequent lecturer turnover. DISCUSSION: A fully integrated tobacco curriculum for medical schools was piloted and is now freely available online. An important lesson learned in Indonesia was that a tobacco curriculum must be flexible enough to be adjusted when shifts in medical education take place. The curriculum is a resource for medical colleges and expert committees in Southeast Asia deliberating how best to address lifestyle factors undermining population health. PMID- 26996641 TI - Facebook as a learning environment for teaching medical emergencies in dental practice. AB - BACKGROUND: Social media can be part of the formal education of health professsionals and in their lifelong learning activities. The effectiveness of Facebook, an online social medium, application for educational purposes was evaluated in this study. It was used to serve as a teaching medium of a course in medical emergencies in dental practice (MEDP). METHODS: Syrian dental students were invited to join a Facebook group "Medical emergencies in dental practice" during the second semester of the academic year 2013-2014. The group privacy settings were changed from an open group to a closed group after the registration period. Administrators of the group published 61 posts during the course period, which extended for one month. Students' progress in learning was evaluated using self-assessment questionnaires administered to the students before and after the course. These questionnaires also queried their opinions regarding the use of Facebook as an educational modality. Qualitative statistics, Wilcoxon signed ranks and Mann-Whitney U-tests were used to analyze the data. RESULTS: Out of 388 students registered in this course, 184 completed it. Two-third of students agreed that Facebook was useful in education. Their impressions of this course were 17.4% as excellent, 52.2% as very good. P values of the self-assessment questions of Wilcoxon signed ranks test were <0.001, indicating self-assessed improvement in MEDP skills. DISCUSSION: Facebook as a social medium provides a unique learning environment. It allows students to discuss topics more openly in a flexible setting with less rigid time and place constraints. In the light of this study it was found that Facebook may be useful in teaching medical emergencies in dental practice in its theoretical aspect. PMID- 26996642 TI - The promise of home visitation by community health workers in rural Kenya: A protective effect that reduces neonatal illness. AB - BACKGROUND: Nearly three million neonates die each year, largely from preventable illnesses in developing countries. Sub-Saharan Africa has disproportionately high neonatal mortality. Community health worker (CHW) programs are a promising intervention to reduce mortality rates. This research evaluates a CHW newborn home visitation program in rural Kenya by assessing the frequency of health service utilization and overnight hospitalization. METHODS: This quasi experimental study encompassed two consecutive years and compared the rate of medical service utilization for neonatal illness in an intervention group with that of a control group using a household survey. Severity of neonatal illness was assessed by need for overnight hospitalization. Household, maternal, and child characteristics were collected. RESULTS: A total of 489 surveys were completed and showed that 35% of not-visited families reported taking their infant to a healthcare facility, compared with 21% of CHW-visited families (P < 0.01). Rates of overnight hospitalization were 6% for not-visited infants and 1% for visited infants (P < 0.01). Few significant differences were found in household, maternal, and child characteristics. DISCUSSION: This study found that a CHW newborn home visitation program in rural Kenya significantly decreased rates of health service utilization and overnight hospitalization, but did not have the power to detect an effect on neonatal mortality. PMID- 26996643 TI - Effectiveness of an online Problem-Based learning curriculum for training family medical doctors in Brazil. AB - BACKGROUND: Problem-based learning (PBL) and distance education (DE) have been combined as educational approaches in higher education. This combination has been called distributed PBL. In health professions education it has been called online PBL (OPBL). However, more research on the effectiveness of OPBL is needed. The present study aims at evaluating the effectiveness of an OPBL curriculum for training family medical doctors in Brazil. METHODS: We used a pretest-posttest control group design in this study. Thirty family physician participants were non randomly assigned to the experimental group and the same number to the control group. Three instruments for collecting data were used: A multiple choice question knowledge test, an Objective Structural Clinical Examination (OSCE) for assessing the ability to apply the Mini Mental State Exam (MMSE) and a test based on clinical cases for assessing the ability to make an adequate differential diagnosis of dementia. Multivariate Analysis of Variance (MANOVA) and univariate tests were conducted to see if the difference between the two groups was significant. The effect size was measured by Cohen's d. RESULTS: A total of 50 participants completed the study. The results show significant effects of the course on participants' knowledge and diagnostic skills. DISCUSSION: The results may indicate that innovative pedagogical approaches such as PBL can be effective in an online environment in a low-resources context, with the advantages of DE approach. PMID- 26996644 TI - An Enhancement-focused framework for developing high quality single best answer multiple choice questions. AB - BACKGROUND: The primary goal of any assessment of students is to provide valid and reliable evaluations of students' knowledge and skills as well as provision of accurate feedback to students about their performance. Contrary to best practice guidelines for development of multiple choice questions (MCQs), however, items used within medical schools are often flawed. This disappoints students and discourages examiners from using in-house MCQ databases. Vetting and reviewing items can improve the quality of MCQs. In this paper, we describe our approach to standardize the format used for MCQ assessment and provide recommendations for quality enhancement of high-stakes assessment. METHODS: A collaborative enhancement-focused vetting and review approach to development of high quality single best answer MCQs has been described. RESULTS: Implementation of a collaborative strategy to blueprint, vet, review and standard set MCQ items for high stakes examinations can effectively contribute to assessment quality assurance. Similarly, shared responsibility for post examination analyses of items may reveal the psychometric properties of items in need of improvement and contribute to closure of the assessment outcomes feedback loop. DISCUSSION: Devolving responsibility for implementation of assessment processes as an integral part of educational practices and values can maximize reliability and standards of assessment processes. We contend that while logistics and time constraints are of concern to busy faculty members, judicious utilization of resources to develop well-written MCQ items are well worth the effort to produce reliable and valid examinee scores. An enhancement-focused approach can be institutionally rewarding and lead to improved quality of high stakes assessments. PMID- 26996645 TI - A suicide awareness and intervention program for health professional students. AB - BACKGROUND: Many emergency service professionals and health professionals play important roles in the assessment and management of suicide risk but often receive inadequate mental health training in this area. A 'Suicide Awareness and Intervention Program' (SAIP) was developed for first year medical, paramedical and pharmacy students at the University of Tasmania, Australia. The program aimed to increase students' knowledge and awareness about suicide-related issues, develop interpersonal skills around suicide screening and increase awareness of available support services. METHODS: A 5-hour experiential SAIP was embedded within the curriculum. A pre and post evaluation of knowledge, skills and attitudes was conducted, with an open-ended follow-up survey regarding use of what was learned in the program. RESULTS: Pre and post SAIP surveys showed significant improvement inknowledge and practical skills. Feedback from students and the counselling service indicated enduring impact of the program. DISCUSSION: Participation in the SAIP increased knowledge, skills and attitudes related to the assessment and management of individuals at risk for suicide, and the application of this ability to students' personal and professional lives. PMID- 26996646 TI - Teaching internal medicine in the community. AB - BACKGROUND: Teaching Internal Medicine is mainly hospital-based. Chronic diseases are treated mostly in community-based ambulatory care. This study describes our experience during the first year of teaching Internal Medicine in the community, with a focus on chronic disease management. METHODS: This was an observational study describing the content of clinical exposure and the feedback from students after a two-week clerkship in community health centers. RESULTS: Over a period of three months, 54 students spent two weeks in health centers singly or in pairs. The disciplines covered were: Endocrinology, Gastroenterology, Pulmonology, Rheumatology and Geriatrics. In their feedback, the students most frequently noted knowledge acquired in the management of diabetes, infectious diseases and cardiology. The teaching content was determined by the case-mix of patients. The spectrum of conditions was wide. Students who were used to more structured hospital-based study found it difficult to cope with this mode of learning by discovery. DISCUSSION: Future research should concentrate on the transition between the different modes of learning as students move from the hospital to the community setting. PMID- 26996647 TI - Comparison of quality of life between medical students and young general populations. AB - BACKGROUND: During the course of their education, medical students learn to attend to the quality of life of their patients. However, their own quality of life can begin to decrease early in medical school. The purpose of this study was to compare the quality of life of medical students to that of others their age, taking into account the medical school phase and gender. METHODS: We used the short version of the World Health Organization Quality of Life Instrument to assess psychological well-being, physical health, social relationships and environmental conditions. The quality of life among 206 medical students was compared to that of 199 young people from a normative population using independent sample t- tests. In addition, the effects of medical school phase and gender on quality of life domains were also assessed by two-way between-groups analysis of variance. RESULTS: Medical students showed worse psychological well being and social relationships than young people in the normative sample. About one-half of the students revealed a low quality of life in the psychological and social domains and one-quarter showed a low quality of life in the physical health and environment domains. Medical school phase did not influence quality of life, however, gender had a large effect, where female students showed worse physical and psychological well-being than male students. DISCUSSION: Poor psychological well-being and social relationships can have implications that exceed the doctor's personal well-being. Future doctors with a low quality of life may translate into their poorer performance, impairing patient care. PMID- 26996648 TI - Public hearing on the first naturopathy curriculum in Thailand. PMID- 26996649 TI - Yoga: A good way for dentists to relieve stress. PMID- 26996650 TI - Enhancing learning in anatomy lectures. PMID- 26996651 TI - Subspecialization in psychiatry: Does it fit with India's need? PMID- 26996652 TI - A completely controlled sphere-to-bilayer micellar transition: the molecular mechanism and application on the growth of nanosheets. AB - The combination of a simple modification of the sample addition method to generate a sort of continuously accumulated external stimulation with only minute increments in amplitude and the introduction of probe molecules (herein aniline) within the micelle allow the direct continuous in situ spectroscopic monitoring of possible micellar transitions. In this way, a sphere-to-ellipsoid and further an ellipsoid-to-bilayer micellar transition of sodium dodecyl sulfate (SDS) induced by camphor sulfuric acid (CSA) is observed to experience four stages in the time sequence: (i) the accumulated protons released from CSA in the hydration layer of the micelle stimulate the rearrangement of SDS micelles; (ii) the micelles transform into ellipsoidal shapes as evidenced by the characteristic chemical shift anisotropy and the corresponding molecular dynamic properties from probe molecules; (iii) further protonation of aniline induces the micelle to turn into lamellar structures; (iv) aniline is freed from the micelle while leaving the SDS bilayers undistorted. Moreover, polyaniline nanosheets incorporating SDS bilayers in sandwich structures, which can display excellent capacitive behavior at relatively high current densities for the fabricated supercapacitors, are prepared from the aniline oriented by the bending energy of the SDS bilayers. PMID- 26996653 TI - Anti-Mur as the most likely cause of mild hemolytic disease of the newborn. AB - BACKGROUND: Although rare in the United States, anti-Mur is relatively common in Southeast Asia and has been reported to have clinical significance in Chinese and Taiwanese populations. STUDY DESIGN AND METHODS: The infant was full term and the second child of a Chinese mother and Vietnamese father, presenting with jaundice. He was clinically diagnosed with immune-mediated hemolytic anemia. RESULTS: The direct antiglobulin test indicated that the infant's red blood cells were coated only with anti-IgG. Anti-Mur was identified in the maternal serum and the neonate's plasma. The father was found to be positive for the Mur antigen. The cause of the infant's hemolytic anemia was determined to be most likely anti-Mur. CONCLUSION: Since anti-Mur is implicated in causing hemolytic disease of the newborn, it is important to recognize this antibody more commonly found in Asian patients in the United States as the Mur+ phenotype has a higher prevalence in this population. PMID- 26996655 TI - Prediction of methane emission from lactating dairy cows using milk fatty acids and mid-infrared spectroscopy. AB - Enteric methane (CH4 ) production is among the main targets of greenhouse gas mitigation practices for the dairy industry. A simple, robust and inexpensive measurement technique applicable on a large scale to estimate CH4 emission from dairy cattle would therefore be valuable. Milk fatty acids (MFA) are related to CH4 production because of the common biochemical pathway between CH4 and fatty acids in the rumen. A summary of studies that investigated the predictive power of MFA composition for CH4 emission indicated good potential, with predictive power ranging between 47% and 95%. Until recently, gas chromatography (GC) was the principal method used to determine the MFA profile, but GC is unsuitable for routine analysis. This has led to the application of mid-infrared (MIR) spectroscopy. The major advantages of using MIR spectroscopy to predict CH4 emission include its simplicity and potential practical application at large scale. Disadvantages include the inability to predict important MFA for CH4 prediction, and the moderate predictive power for CH4 emission. It may not be sufficient to predict CH4 emission based on MIR alone. Integration with other factors, like feed intake, nutrient composition of the feed, parity, and lactation stage may improve the prediction of CH4 emission using MIR spectra. (c) 2016 Society of Chemical Industry. PMID- 26996654 TI - Ecological and evolutionary significance of novel protist lineages. AB - Environmental molecular surveys targeting protist diversity have unveiled novel and uncultured lineages in a variety of ecosystems, ranging from completely new high-rank lineages, to new taxa moderately related to previously described organisms. The ecological roles of some of these novel taxa have been studied, showing that in certain habitats they may be responsible for critical environmental processes. Moreover, from an evolutionary perspective they still need to be included in a more accurate and wider understanding of the eukaryotic tree of life. These seminal discoveries promoted the development and use of a wide range of more in-depth culture-independent approaches to access this diversity, from metabarcoding and metagenomics to single cell genomics and FISH. Nonetheless, culturing using classical or innovative approaches is also essential to better characterize this new diversity. Ecologists and evolutionary biologists now face the challenge of apprehending the significance of this new diversity within the eukaryotic tree of life. PMID- 26996656 TI - Diagnostic performance of HbA1c for diabetes in Arab vs. European populations: a systematic review and meta-analysis. AB - AIM: To examine differences in the performance of HbA1c for diagnosing diabetes in Arabs compared with Europeans. METHODS: The PubMed, Embase and Cochrane library databases were searched for records published between 1998 and 2015. Estimates of sensitivity, specificity and log diagnostic odds ratios for an HbA1c cut-point of 48 mmol/mol (6.5%) were compared between Arabs and Europeans, using a bivariate linear mixed-model approach. For studies reporting multiple cut points, population-specific summary receiver operating characteristic (SROC) curves were constructed. In addition, sensitivity, specificity and Youden Index were estimated for strata defined by HbA1c cut-point and population type. Database searches yielded 1912 unique records; 618 full-text articles were reviewed. Fourteen studies met the inclusion criteria; hand-searching yielded three additional eligible studies. Three Arab (N = 2880) and 16 European populations (N = 49 127) were included in the analysis. RESULTS: Summary sensitivity and specificity for a HbA1c cut-point of 48 mmol/mol (6.5%) in both populations were 42% (33-51%), and 97% (95-98%). There was no difference in area under SROC curves between Arab and European populations (0.844 vs. 0.847; P = 0.867), suggesting no difference in HbA1c diagnostic accuracy between populations. Multiple cut-point summary estimates stratified by population suggest that Arabs have lower sensitivity and higher specificity at a HbA1c cut point of 44 mmol/mol (6.2%) compared with European populations. Estimates also suggest similar test performance at cut-points of 44 mmol/mol (6.2%) and 48 mmol/mol (6.5%) for Arabs. CONCLUSIONS: Given the low sensitivity of HbA1c in the high-risk Arab American population, we recommend a combination of glucose-based and HbA1c testing to ensure an accurate and timely diagnosis of diabetes. PMID- 26996657 TI - Combination of simvastatin, calcium silicate/gypsum, and gelatin and bone regeneration in rabbit calvarial defects. AB - The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration. PMID- 26996658 TI - 23327Enhanced photoelectric conversion efficiency of dye-sensitized solar cells by the incorporation of flower-like Bi2S3:Eu3+ sub-microspheres. AB - In this paper, TiO2-Bi2S3 and TiO2-Bi2S3:Eu(3+) composite photoanodes were successfully designed, which can not only fully absorb visible light but also transfer the electron from Bi2S3 to TiO2 conduction band due to the narrow band gap and high conduction band of Bi2S3. Compared to pure TiO2 cell, the photoelectric conversion efficiencies of TiO2-Bi2S3 and TiO2-Bi2S3:Eu(3+) composite cells were increased significantly. In addition, the efficiency of TiO2 Bi2S3:Eu(3+) composite cells were higher than that of TiO2-Bi2S3 cell which could be attributed to the larger BET surface area of Bi2S3:Eu(3+). The electron transport and interfacial recombination kinetics were investigated by the electrochemical impedance spectroscopy and intensity-modulated photocurrent/photovoltage spectroscopy. The results indicated that the interfacial resistance of the TiO2-dye|I3(-)/I(-) electrolyte interface of TiO2 Bi2S3:Eu(3+) composite cell was much bigger than that of pure TiO2 cell. In addition, the TiO2-Bi2S3:Eu(3+) cell has longer electron recombination time and longer electron transport time than pure TiO2 cell. The charge collection efficiency of TiO2-Bi2S3:Eu(3+) composite cell was higher than that of pure TiO2 cell. PMID- 26996659 TI - The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. AB - It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report. PATIENT SUMMARY: Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential. PMID- 26996660 TI - Pathology and Genetics: Tumours of the Urinary System and Male Genital System: Clinical Implications of the 4th Edition of the WHO Classification and Beyond. PMID- 26996662 TI - Rajavithi-ovarian cancer predictive score (R-OPS): A new scoring system for predicting ovarian malignancy in women presenting with a pelvic mass. AB - OBJECTIVE: To develop a new scoring system based on menopausal status, ultrasound (US) findings, serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to predict ovarian cancer (OC) in women presenting with a pelvic or adnexal mass. METHODS: Consecutive female patients aged over 18years with pelvic or adnexal masses investigated preoperatively by pelvic US, serum CA125 and HE4 who underwent elective surgery were enrolled. The "Rajavithi-Ovarian Cancer Predictive Score (R-OPS)" was developed using data from 2012 and validated using data from 2013 to 2014. The diagnosis of OC was based on pathological findings. Data were analyzed by logistic regression and area under the receiver operating characteristic curve (ROC-AUC). RESULTS: Based on a development set of 260 women including 74 with OC, menopausal status (M), serum CA125 and HE4, and US findings of solid lesions (U) were identified as significant predictors of OC. R OPS=M*U*(CA125*HE4)(1/2) revealed good calibration (goodness-of-fit test, p=0.972) and discrimination (ROC-AUC=92.8%). Performance validation in 266 women, 82 with OC, showed good discrimination with ROC-AUC of 94.9%. Performance in the validation sample with a cutoff value of R-OPS>330 revealed sensitivity, specificity, and positive and negative predictive values of 93.9%, 79.9%, 67.5%, and 96.7%, respectively. CONCLUSIONS: The new R-OPS scoring system showed good discrimination between non-cancerous lesions and OC. However, a prospective study in a different setting is required to confirm these preliminary data. PMID- 26996661 TI - Late Relapses in Stage I Testicular Cancer Patients on Surveillance. AB - BACKGROUND: Comprehensive data on late relapse (LR) and very LR (VLR) in patients with clinical stage I (CS-1) testicular cancer followed on surveillance are missing. These data are essential for planning optimal follow-up. OBJECTIVE: Assess incidence and outcome of LR (>2 yr) and VLR (>5 yr) in a large cohort of CS-1 surveillance patients, and examine differences in the clinical characteristics of patients with early relapse (ER), LR, and VLR. DESIGN, SETTING, AND PARTICIPANTS: CS-1 surveillance patients diagnosed between 1984 and 2007 were identified from the retrospective Danish Testicular Cancer (DaTeCa) database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We estimated survival and relapse probabilities and compared the results using log-rank tests and Cox regression analyses. We compared differences in patient characteristics by using chi(2), Fisher exact, and Mann-Whitney tests. RESULTS AND LIMITATIONS: Our study included 3366 (2000 seminoma and 1366 nonseminoma) patients. Median follow-up was 15 yr. Five-year conditional risk of LR was 5.0% and 2.1% for seminoma and nonseminoma patients, respectively. There were no significant differences in disease-specific or overall survival when comparing the LR(VLR) and ER patients by log-rank, but Cox regression adjusted for age showed a significant effect of time to relapse on survival for seminoma patients. Apart from significantly more ER nonseminoma patients with elevated human chorionic gonadotropin at relapse, there were no significant differences in patient characteristics at orchiectomy or relapse. Limitations include retrospective design and exclusion of patients who had been offered adjuvant therapy. CONCLUSIONS: The risk of VLR is minimal, and the patients carry a good prognosis. Patient characteristics of CS-1 surveillance patients with LR(VLR) do not differ significantly from patients with ER. PATIENT SUMMARY: We compared stage I testicular cancer surveillance patients with early relapse (ER) versus late relapse (LR; >2 yr). LR patients as a group did no worse than ER patients, although increased time to relapse was negatively associated with survival for seminoma patients. PMID- 26996663 TI - Collagen-rich stroma in aggressive colon tumors induces mesenchymal gene expression and tumor cell invasion. AB - Gene expression-based classification systems have identified an aggressive colon cancer subtype with mesenchymal features, possibly reflecting epithelial-to mesenchymal transition (EMT) of tumor cells. However, stromal fibroblasts contribute extensively to the mesenchymal phenotype of aggressive colon tumors, challenging the notion of tumor EMT. To separately study the neoplastic and stromal compartments of colon tumors, we have generated a stroma gene filter (SGF). Comparative analysis of stromahigh and stromalow tumors shows that the neoplastic cells in stromahigh tumors express specific EMT drivers (ZEB2, TWIST1, TWIST2) and that 98% of differentially expressed genes are strongly correlated with them. Analysis of differential gene expression between mesenchymal and epithelial cancer cell lines revealed that hepatocyte nuclear factor 4alpha (HNF4alpha), a transcriptional activator of intestinal (epithelial) differentiation, and its target genes are highly expressed in epithelial cancer cell lines. However, mesenchymal-type cancer cell lines expressed only part of the mesenchymal genes expressed by tumor-derived neoplastic cells, suggesting that external cues were lacking. We found that collagen-I dominates the extracellular matrix in aggressive colon cancer. Mimicking the tumor microenvironment by replacing laminin-rich Matrigel with collagen-I was sufficient to induce tumor-specific mesenchymal gene expression, suppression of HNF4alpha and its target genes, and collective tumor cell invasion of patient derived colon tumor organoids. The data connect collagen-rich stroma to mesenchymal gene expression in neoplastic cells and to collective tumor cell invasion. Targeting the tumor-collagen interface may therefore be explored as a novel strategy in the treatment of aggressive colon cancer. PMID- 26996664 TI - A platform for interrogating cancer-associated p53 alleles. AB - p53 is the most frequently mutated gene in human cancer. Compelling evidence argues that full transformation involves loss of growth suppression encoded by wild-type p53 together with poorly understood oncogenic activity encoded by missense mutations. Furthermore, distinguishing disease alleles from natural polymorphisms is an important clinical challenge. To interrogate the genetic activity of human p53 variants, we leveraged the Drosophila model as an in vivo platform. We engineered strains that replace the fly p53 gene with human alleles, producing a collection of stocks that are, in effect, 'humanized' for p53 variants. Like the fly counterpart, human p53 transcriptionally activated a biosensor and induced apoptosis after DNA damage. However, all humanized strains representing common alleles found in cancer patients failed to complement in these assays. Surprisingly, stimulus-dependent activation of hp53 occurred without stabilization, demonstrating that these two processes can be uncoupled. Like its fly counterpart, hp53 formed prominent nuclear foci in germline cells but cancer-associated p53 variants did not. Moreover, these same mutant alleles disrupted hp53 foci and inhibited biosensor activity, suggesting that these properties are functionally linked. Together these findings establish a functional platform for interrogating human p53 alleles and suggest that simple phenotypes could be used to stratify disease variants. PMID- 26996665 TI - The Delta133p53 isoform and its mouse analogue Delta122p53 promote invasion and metastasis involving pro-inflammatory molecules interleukin-6 and CCL2. AB - A number of naturally occurring isoforms of the tumour suppressor protein p53 have been discovered, which appear to have differing roles in tumour prevention or promotion. We are investigating the tumour-promoting activities of the Delta133p53 isoform using our mouse model of Delta133p53 (Delta122p53). Here, we report that tumours from Delta122p53 homozygous mice show evidence of invasion and metastasis and that Delta122p53 promotes migration though a 3-dimensional collagen matrix. We also show that Delta122p53 and Delta133p53 promote cell migration in scratch wound and Transwell assays, similar to the 'gain-of function' phenotypes seen with mutant p53. Using the well-defined B16 mouse melanoma metastatic model, we show that Delta122p53 leads to faster generation of lung metastases. The increased migratory phenotypes are dependent on secreted factors, including the cytokine interleukin-6 and the chemokine CCL2. We propose that Delta122p53 (and Delta133p53) acts in a similar manner to 'gain-of-function' mutant p53 proteins to promote migration, invasion and metastasis, which may contribute to poor survival in patients with Delta133p53-expressing tumours. PMID- 26996666 TI - Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE. AB - Cancer invasion is a hallmark of metastasis. The mesenchymal mode of cancer cell invasion is mediated by elongated membrane protrusions driven by the assembly of branched F-actin networks. How deregulation of actin regulators promotes cancer cell invasion is still enigmatic. We report that increased expression and membrane localization of the actin regulator Lamellipodin correlate with reduced metastasis-free survival and poor prognosis in breast cancer patients. In agreement, we find that Lamellipodin depletion reduced lung metastasis in an orthotopic mouse breast cancer model. Invasive 3D cancer cell migration as well as invadopodia formation and matrix degradation was impaired upon Lamellipodin depletion. Mechanistically, we show that Lamellipodin promotes invasive 3D cancer cell migration via both actin-elongating Ena/VASP proteins and the Scar/WAVE complex, which stimulates actin branching. In contrast, Lamellipodin interaction with Scar/WAVE but not with Ena/VASP is required for random 2D cell migration. We identified a phosphorylation-dependent mechanism that regulates selective recruitment of these effectors to Lamellipodin: Abl-mediated Lamellipodin phosphorylation promotes its association with both Scar/WAVE and Ena/VASP, whereas Src-dependent phosphorylation enhances binding to Scar/WAVE but not to Ena/VASP. Through these selective, regulated interactions Lamellipodin mediates directional sensing of epidermal growth factor (EGF) gradients and invasive 3D migration of breast cancer cells. Our findings imply that increased Lamellipodin levels enhance Ena/VASP and Scar/WAVE activities at the plasma membrane to promote 3D invasion and metastasis. PMID- 26996668 TI - The presence of C/EBPalpha and its degradation are both required for TRIB2 mediated leukaemia. AB - C/EBPalpha (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPalpha p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML transformation is not known and the molecular mechanism involved remains elusive. Using mouse genetics, our data reveal that in the complete absence of C/EBPalpha, TRIB2 was unable to induce AML. Only in the presence of C/EBPalpha p42 and p30, were TRIB2 and p30 able to cooperate to decrease the latency of disease. We demonstrate that the molecular mechanism involved in the degradation of C/EBPalpha p42 requires site-specific direct interaction between TRIB2 and C/EBPalpha p42 for the K48-specific ubiquitin-dependent proteasomal degradation of C/EBPalpha p42. This interaction and ubiquitination is dependent on a critical C terminal lysine residue on C/EBPalpha. We show effective targeting of this pathway pharmacologically using proteasome inhibitors in TRIB2-positive AML cells. Together, our data show that excess p30 cooperated with TRIB2 only in the presence of p42 to accelerate AML, and the direct interaction and degradation of C/EBPalpha p42 is required for TRIB2-mediated AML. PMID- 26996667 TI - BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways. AB - Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole-genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB. PMID- 26996669 TI - Mutant p53 inhibits miRNA biogenesis by interfering with the microprocessor complex. AB - Downregulation of microRNAs (miRNAs) is commonly observed in cancers and promotes tumorigenesis suggesting that miRNAs may function as tumor suppressors. However, the mechanism through which miRNAs are regulated in cancer, and the connection between oncogenes and miRNA biogenesis remain poorly understood. The TP53 tumor suppressor gene is mutated in half of human cancers resulting in an oncogene with gain-of-function activities. Here we demonstrate that mutant p53 (mutp53) oncoproteins modulate the biogenesis of a subset of miRNAs in cancer cells inhibiting their post-transcriptional maturation. Interestingly, among these miRNAs several are also downregulated in human tumors. By confocal, co immunoprecipitation and RNA-chromatin immunoprecipitation experiments, we show that endogenous mutp53 binds and sequesters RNA helicases p72/82 from the microprocessor complex, interfering with Drosha-pri-miRNAs association. In agreement with this, the overexpression of p72 leads to an increase of mature miRNAs levels. Moreover, functional experiments demonstrate the oncosuppressive role of mutp53-dependent miRNAs (miR-517a, -519a, -218, -105). Our study highlights a previously undescribed mechanism by which mutp53 interferes with Drosha-p72/82 association leading, at least in part, to miRNA deregulation observed in cancer. PMID- 26996672 TI - High education and increased parity are associated with breast-feeding initiation and duration among Australian women. AB - OBJECTIVE: Breast-feeding is associated with positive maternal and infant health and development outcomes. To assist identifying women less likely to meet infant nutritional guidelines, we investigated the role of socio-economic position and parity on initiation of and sustaining breast-feeding for at least 6 months. DESIGN: Prospective cohort study. SETTING: Australia. SUBJECTS: Parous women from the Australian Longitudinal Study on Women's Health (born 1973-78), with self reported reproductive and breast-feeding history (N 4777). RESULTS: While 89 % of women (83 % of infants) had ever breast-fed, only 60 % of infants were breast-fed for at least 6 months. Multiparous women were more likely to breast-feed their first child (~90 % v. ~71 % of primiparous women), and women who breast-fed their first child were more likely to breast-feed subsequent children. Women with a low education (adjusted OR (95 % CI): 2.09 (1.67, 2.62)) or a very low-educated parent (1.47 (1.16, 1.88)) had increased odds of not initiating breast-feeding with their first or subsequent children. While fewer women initiated breast feeding with their youngest child, this was most pronounced among high-educated women. While ~60 % of women breast-fed their first, second and third child for at least 6 months, low-educated women (first child, adjusted OR (95 % CI): 2.19 (1.79, 2.68)) and women with a very low (1.82 (1.49, 2.22)) or low-educated parent (1.69 (1.33, 2.14)) had increased odds of not breast-feeding for at least 6 months. CONCLUSIONS: A greater understanding of barriers to initiating and sustaining breast-feeding, some of which are socio-economic-specific, may assist in reducing inequalities in infant breast-feeding. PMID- 26996673 TI - Tobacco and Alcohol Use in People With Mild/Moderate Intellectual Disabilities: Giving Voice to Their Health Promotion Needs. AB - BACKGROUND: Concerns have been raised about the use/misuse of tobacco and alcohol by people with mild/moderate intellectual disabilities. Aiming to address an identified gap in the current evidence base, this study sought to gain an understanding of the tobacco- and alcohol-related health promotion needs of this client group. METHODS: Informed by the principles of social cognitive theory, data were collected using focus group and telephone interviews. Participants were 16 people with intellectual disabilities, two family carers and 15 health and social care professionals. Data were analysed using the Framework approach. FINDINGS: Four themes were described: being like others; social and emotional influences; understandings, misunderstandings and learning from experience; and choices and challenges. Reasons for smoking and drinking alcohol echoed those of the general population; however, health promotion needs were more complex (e.g. linked to problems with consequential thinking; low levels of self-efficacy). CONCLUSION: This article provides insight into the tobacco- and alcohol-related health promotion needs of people with intellectual disabilities. There is a need for integrated service provision that addresses both personal and environmental influences on behaviour. PMID- 26996671 TI - Akt regulates progesterone receptor B-dependent transcription and angiogenesis in endometrial cancer cells. AB - Progestins have long been used clinically for the treatment of endometrial cancers; however, the response rates to progestin therapy vary and the molecular mechanisms behind progestin insensitivity are poorly understood. We hypothesized that in PTEN-mutated endometrial cancers, hyperactive Akt signaling downregulates progesterone receptor B (PRB) transcriptional activity, leading to overall impaired progestin responses. We report that inhibition of Akt with the Akt inhibitor, MK-2206 (MK), in conjunction with progestin (R5020) treatment, is sufficient to upregulate a subset of PRB target genes in Ishikawa cells stably expressing PRB (PRB-Ishikawa). Through gene ontology analysis of Akt-regulated PRB target genes, angiogenesis was found to be the principle process regulated by Akt-PRB. To further interrogate the mechanism by which Akt modulates PRB transcriptional activity, ChIP-Mass spectrometry was performed to identify potential cofactors that differentially interact with PRB in the presence of R5020 and MK+R5020. 14-3-3sigma was identified as a protein enriched in the MK+R5020 data set, and it was demonstrated that 14-3-3sigma is required for the upregulation in PRB target gene expression following inhibition of Akt. To determine the ramifications of MK+R5020 treatment on angiogenesis, in vitro assays were performed and combinatorial MK+R5020 treatment significantly decreased endothelial cell invasion and tube formation more than MK or R5020 treatment alone. Furthermore, we found that combinatorial MK-2206+progesterone treatments decreased angiogenesis and proliferation in the Pten(d/d) conditional mouse model of endometrial cancer. Taken together, these findings suggest that a combinatorial therapeutic approach utilizing Akt inhibitors with progestins may improve the efficacy of progestin therapy for the treatment of endometrial cancer. PMID- 26996675 TI - Intraoperative Adductor Canal Block for Augmentation of Periarticular Injection in Total Knee Arthroplasty: A Cadaveric Study. AB - BACKGROUND: Function is often sacrificed for pain control after total knee arthroplasty. Motor-sparing blocks, including adductor canal block (ACB) and periarticular injection (PAI), have gained interest to address this compromise. Our study evaluates the anatomic feasibility, accuracy, and safety of intraoperative ACB as an adjunct to PAI by analyzing 3 different injection orientations and needle configurations. METHODS: Eleven cadaveric knees underwent a standard medial parapatellar arthrotomy. Blunt dissection through the suprapatellar recess was performed. Using a 10-mL syringe, various colors of dyed liquid gelatin were injected toward the proximal and distal adductor canal (AC) using 3 needle configurations. Medial dissection of the knee for each specimen was performed. The position of each needle and location of injected dye was identified and described relative to the AC. RESULTS: Accuracy of each injection orientation and/or needle configuration was different: 86% for a blunt needle in the distal AC, 57% for blunt needle in the proximal AC, and 14% for a spinal needle in the proximal AC. Puncture of the femoral artery was observed with the spinal needle 43% of the time and had the closest average proximity to the femoral artery with a distance of 5.9 mm. There were no vascular punctures using blunt needles, and the average distance from the femoral artery with proximal and distal orientation was 10.2 mm and 15.4 mm, respectively. CONCLUSION: Intraoperative ACB augmentation of PAI appears to be anatomically feasible and safe. There was decreased accuracy and increased risk of vascular puncture using a 3.5-inch spinal needle. A blunt 1.5-inch needle directed toward the distal AC had the highest accuracy while minimizing vascular injury. PMID- 26996676 TI - Risk Factors for Adolescent Drinking: An Introduction. PMID- 26996670 TI - Preclinical and clinical evaluation of MET functions in cancer cells and in the tumor stroma. AB - A lot of attention has been dedicated to investigate the role of the tyrosine kinase receptor MET in tumors. The acquired notion that cancer cells from different histological origin strictly rely on the engagement of this specific oncogene for their growth and survival has certainly justified the development and the use of MET-targeted therapies in the clinic. However, the function and involvement of this pathway in the stroma (that often constitutes >50% of the global cellularity of the tumor) may offer the opportunity to conceive new patient stratification criteria, rational drug design and guided trials of new combination treatments. In this review, we will summarize and discuss the role of MET in cancer cells but especially in different stromal compartments, in light of the results showed by past and recent preclinical and clinical trials with anti MET drugs. PMID- 26996674 TI - Controllable positive exchange bias via redox-driven oxygen migration. AB - Ionic transport in metal/oxide heterostructures offers a highly effective means to tailor material properties via modification of the interfacial characteristics. However, direct observation of ionic motion under buried interfaces and demonstration of its correlation with physical properties has been challenging. Using the strong oxygen affinity of gadolinium, we design a model system of GdxFe1-x/NiCoO bilayer films, where the oxygen migration is observed and manifested in a controlled positive exchange bias over a relatively small cooling field range. The exchange bias characteristics are shown to be the result of an interfacial layer of elemental nickel and cobalt, a few nanometres in thickness, whose moments are larger than expected from uncompensated NiCoO moments. This interface layer is attributed to a redox-driven oxygen migration from NiCoO to the gadolinium, during growth or soon after. These results demonstrate an effective path to tailoring the interfacial characteristics and interlayer exchange coupling in metal/oxide heterostructures. PMID- 26996677 TI - ZnCo2 O4 Quantum Dots Anchored on Nitrogen-Doped Carbon Nanotubes as Reversible Oxygen Reduction/Evolution Electrocatalysts. AB - ZnCo2 O4 quantum dots anchored on nitrogen-doped carbon nanotubes (N-CNT) retain the high catalytic activity of ZnCo2 O4 to oxidize water while enabling an efficient oxygen reduction performance thereby combining these desirable features. These advantages realize a bifunctional catalytic activity for ZnCo2 O4 /N-CNT that can be used in rechargeable zinc-air batteries. PMID- 26996721 TI - Surgical outcome of cats treated for aqueous humor misdirection syndrome: a case series. AB - OBJECTIVE: To evaluate the clinical outcome of cats treated surgically for aqueous humor misdirection syndrome. METHODS: A retrospective analysis of cats treated surgically between January 1, 2006, and January 1, 2013, for aqueous humor misdirection syndrome was performed. Signalment, medical therapy, eyes affected, intraocular pressures prior to and after surgery, surgical procedures performed, postoperative complications, and visual status were evaluated. RESULTS: Seven cats (nine eyes) fit the inclusion criteria. Six of seven cats were female, and five of seven cats were diagnosed with bilateral aqueous humor misdirection syndrome. Three surgical approaches were evaluated as follows: (i) phacoemulsification and posterior capsulotomy, (ii) phacoemulsification, posterior capsulotomy and anterior vitrectomy, and (iii) phacoemulsification, posterior capsulotomy, anterior vitrectomy, and endocyclophotocoagulation. The mean age at diagnosis was 12.9 years. Seven of nine eyes had controlled intraocular pressure (<=25 mmHg) during the first 6 months postoperatively. All cats were visual with controlled intraocular inflammation at 1 year postoperatively; however, one eye had an elevated intraocular pressure. All cats were continued on topical antiglaucoma and anti-inflammatory medications following surgery with the mean number of drops per day decreasing from 3.9 drops/day prior to surgery to 2.2 drops/day postoperatively. CONCLUSIONS: Surgical management for feline aqueous humor misdirection syndrome may be a viable option to maintain a visual and normotensive status in cats that no longer have successful control of intraocular pressure with medical therapy. PMID- 26996722 TI - Correlation between the increased release of catecholamines evoked by local anesthetics and their analgesic and adverse effects: Role of K(+) channel inhibition. AB - Because local anesthetics are known to inhibit both sodium and potassium channels, and anesthetic properties have been attributed to the former effect, we compared their effects with those of tetrodotoxin (TTX), a selective Na(+) channel inhibitor with anesthetic activity, and 4-aminopyridine (4-AP), a selective potassium channel blocker with convulsive activity, on transmitter release during rest and in response to field (axonal) stimulation using the microvolume perfusion method and isolated prefrontal cortex and spinal cord slice preparations loaded with the radioactive transmitters [(3)H]dopamine ([(3)H]DA) and [(3)H]noradrenaline ([(3)H]NA). It is also known that local anesthetics may exert analgesic effect and, rarely, some adverse effects on the central nervous system (CNS). Neurochemical evidence demonstrated that local anesthetics administered at concentrations ranging from 0.5 to 5mM, which might have been intentionally or accidentally achieved in clinical practice (e.g., during spinal and epidural anesthesia or peripheral nerve block), led to presynaptic failures during neurochemical transmission, including inhibited transmitter release associated with axonal firing and markedly enhanced extraneuronal concentrations of transmitters due to increased resting, [Ca(2+)]o-independent release. Tetrodotoxin, a toxin with selective Na(+) channel-blocking properties, inhibited the stimulation-evoked release but failed to affect the resting release. In contrast, the potassium channel inhibitor 4-AP enhanced both the resting- and action potential-evoked transmitter releases. It is concluded that effects of local anesthetics on resting catecholamine release in the spinal cord may contribute to their action during neuropathic pain relief and spinal analgesia as well as to their side effects in the CNS. PMID- 26996723 TI - Inflammatory Markers in Obese Adolescents with Type 2 Diabetes and Their Relationship to Hepatokines and Adipokines. AB - OBJECTIVES: To analyze inflammatory markers, adipokines, and hepatokines in obese adolescents with and without type 2 diabetes mellitus (T2DM). STUDY DESIGN: We studied high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF) alpha, interleukin-1beta, and interferon-gamma, the hepatokines (fetuin-A and fibroblast growth factor [FGF]-21), and the adipokines (adiponectin and leptin) in a cross-sectional study of 74 predominately Caucasian adolescents with T2DM aged 12-18 years and in 74 body mass index (BMI)-, age-, and sex-matched controls. RESULTS: Adolescents with T2DM had significantly higher concentrations of hsCRP, TNF-alpha, and interleukin-1beta compared with obese controls without T2DM. Interferon-gamma was not detectable in obese adolescents with or without T2DM. In multiple linear regression analysis, hsCRP was significantly associated with FGF-21 and BMI, but not with hemoglobin A1c, adiponectin, leptin, fetuin-A, sex, or age. TNF-alpha was significantly related negatively to leptin, positively to BMI, but not to hemoglobin A1c, adiponectin, fetuin-A, FGF-21 sex, or age in multiple linear regression analysis. CONCLUSIONS: Increased inflammatory markers are associated with T2DM in adolescents. Because hsCRP was related to FGF-21 and TNF-alpha was associated with leptin, these findings suggest a link between increased levels of these adipokines and hepatokines and chronic inflammation. Future longitudinal studies in humans are necessary to confirm these hypotheses. PMID- 26996724 TI - Genetics of Hypoplastic Left Heart Syndrome. PMID- 26996725 TI - Cytomegalovirus Meningitis in an Infant with Severe Combined Immunodeficiency. AB - A 35-day-old female with severe combined immunodeficiency developed cytomegalovirus (CMV) meningitis before undergoing hematopoietic stem cell transplantation. Strategies for timely diagnosis of neonates with congenital or acquired CMV infection and prevention of CMV acquisition in the era of universal newborn severe combined immunodeficiency screening are needed. PMID- 26996726 TI - Obesity in early adulthood predicts knee pain and walking difficulties among men: A life course study. AB - BACKGROUND: Few studies have addressed the role of obesity in young adulthood in knee problems later in life. We assessed the associations of overweight/obesity with knee pain and functional limitations of the knee across the life course. METHODS: Military health records from 1967 to 2000 (baseline) were searched for 18- to 50-year-old Finnish men (n = 1913) who participated in the Health 2000 Study (follow-up). Visits to health care were followed during service. Height and weight were measured at baseline and follow-up and waist circumference at follow up. Weight was inquired at follow-up for ages of 20, 30, 40 and 50 years, if applicable. Life course body mass index (BMI) was calculated. One-month knee pain and functional limitations (walking difficulties and limping) due to knee problems were enquired with interview at follow-up. Cox regression model, logistic regression and trajectory analysis were applied. RESULTS: Body mass index at the age of 20 increased the risk of unilateral knee pain by 38% and functional limitations by 27% for one standard deviation increment of BMI, respectively. One-unit increment of Z-score of life course BMI increased knee pain by 32%. Development of severe obesity during the follow-up increased the risk of knee pain by 80% and functional limitations by 93%. The effect of obesity on functional limitations was partly mediated by traumatic knee problems during military service. CONCLUSIONS: Reducing overweight already in adolescence and avoiding further weight gain during life course may prevent knee pain and associated disability. WHAT DOES THIS STUDY ADD?: BMI at the age of 20 increases the likelihood of knee pain and functional limitations of the knee later in life. Development of severe obesity in adulthood increases the risk of knee pain by 80% and functional limitations by more than 90%. Both general and abdominal obesity are associated with knee pain, associations being stronger for general obesity. PMID- 26996727 TI - Preoperative serum alpha-fetoprotein and prognosis after hepatectomy for hepatocellular carcinoma. AB - BACKGROUND: While the majority of studies report that a raised serum alpha fetoprotein (AFP) level before operation is associated with a high risk of recurrence and death in patients who undergo hepatectomy for hepatocellular carcinoma (HCC), results are conflicting. The aim of this study was to assess the prognostic value of AFP. METHODS: Serum AFP levels were measured in patients with hepatitis-associated HCC who underwent hepatectomy between 1995 and 2012. Kaplan Meier and multivariable analyses were performed to identify risk factors for overall and disease-free survival. Univariable and multivariable Cox proportional hazards regression was used to evaluate the predictive value of AFP. Receiver operating characteristic (ROC) curves were generated to identify the AFP level that had the highest accuracy in discriminating between survivors and non survivors. RESULTS: Some 376 patients with hepatitis B virus (HBV)-associated HCC were included in the study. The overall survival rate was 58.8 per cent in patients with an AFP level of 400 ng/ml or less compared with 40.4 per cent for those with a level exceeding 400 ng/ml (P = 0.001). AFP concentration above 400 ng/ml was an independent risk factor for shorter disease-free and overall survival after surgery. ROC analysis indicated that the optimal cut-off values for AFP varied for different subtypes of HCC. The sensitivity and specificity were lower with areas under the ROC curve of less than 0.600. An AFP level greater than 400 ng/ml was not sensitive enough to predict the prognosis in patients with an HCC diameter smaller than 3 cm. CONCLUSION: A serum AFP level above 400 ng/ml predicts poor overall and recurrence-free survival after hepatectomy in patients with HBV-associated HCC. AFP is not a strong prognostic marker given its poor discriminatory power, with low sensitivity and specificity. PMID- 26996728 TI - Cellular response of the blood-brain barrier to injury: Potential biomarkers and therapeutic targets for brain regeneration. AB - Endothelial cells are the main component of the blood-brain barrier (BBB), a vital structure for maintaining brain homeostasis that is seriously disrupted in various neurological pathologies. Therefore, vascular-targeted therapies may bring advantages for the prevention and treatment of brain disorders. In this sense, novel methods to identify and evaluate endothelial damage have been developed and include the detection of circulating endothelial cells, endothelial progenitor cells, endothelial microparticles and exosomes. These cells and cellular structures have been documented in numerous diseases, and increasingly in neurodegenerative disorders, which have led many to assume that they can either be possible biomarkers or tools of repair. Therefore, the purpose of this review is to discuss available data on BBB endothelial damage occurring in two pathologies of the central nervous system, Alzheimer's disease and stroke, which exemplify conditions where chronic and acute vascular damage occur, respectively. The ultimate goal is to identify useful biomarkers and/or therapeutic tools in the healthy and diseased brain that can be used for the treatment of neurodegenerative diseases where BBB permeability and integrity are impaired. PMID- 26996729 TI - Traveling in Other People's Shoes. PMID- 26996730 TI - Reflections on Caring: An Introduction. PMID- 26996731 TI - Genome-wide identification and developmental expression profiling of long noncoding RNAs during Drosophila metamorphosis. AB - An increasing number of long noncoding RNAs (lncRNAs) have been discovered with the recent advances in RNA-sequencing technologies. lncRNAs play key roles across diverse biological processes, and are involved in developmental regulation. However, knowledge about how the genome-wide expression of lncRNAs is developmentally regulated is still limited. We here performed a whole-genome identification of lncRNAs followed by a global expression profiling of these lncRNAs during development in Drosophila melanogaster. We combined bioinformatic prediction of lncRNAs with stringent filtering of protein-coding transcripts and experimental validation to define a high-confidence set of Drosophila lncRNAs. We identified 1,077 lncRNAs in the given transcriptomes that contain 43,967 transcripts; among these, 646 lncRNAs are novel. In vivo expression profiling of these lncRNAs in 27 developmental processes revealed that the expression of lncRNAs is highly temporally restricted relative to that of protein-coding genes. Remarkably, 21% and 42% lncRNAs were significantly upregulated at late embryonic and larval stage, the critical time for developmental transition. The results highlight the developmental specificity of lncRNA expression, and reflect the regulatory significance of a large subclass of lncRNAs for the onset of metamorphosis. The systematic annotation and expression analysis of lncRNAs during Drosophila development form the foundation for future functional exploration. PMID- 26996732 TI - Social Media in Academic Neurosurgery. PMID- 26996733 TI - On the Shoulders of Giants, with a Smartphone: Periscope in Neurosurgery. PMID- 26996734 TI - Concomitant Intracranial Chronic Subdural Hematoma and Spinal Subdural Hematoma: A Case Report and Literature Review. AB - BACKGROUND: Concomitant intracranial chronic subdural hematoma (CSDH) and spinal subdural hematoma (SDH) are rare, and the etiology has yet to be elucidated. However, migration of the hematoma intracranially to a spinal site or coincidence of both intracranial and spinal CSDHs have been proposed as etiologies. We report a case of concomitant intracranial CSDH and spinal SDH in which spinal hematoma might have migrated from the cranial lesion. CASE DESCRIPTION: A previously healthy 58-year-old man with previous trauma to the occiput and lumbar spine suffered from headache, lumbago, and left hemiparesis. Head computed tomography revealed right-sided intracranial CSDH, and he underwent single burr-hole craniotomy. Although clinical symptoms tended to improve, left lower-limb weakness and lumbago remained. Spinal magnetic resonance imaging (MRI) 3 days after craniotomy revealed SDH extending from T1-S1. Because conservative therapy had not improved clinical symptoms, hematoma evacuation was performed via a left L5 hemilaminectomy 1 week after craniotomy. The patient showed complete recovery immediately postoperatively. CONCLUSIONS: We reviewed the cases of 22 patients with concomitant intracranial CSDH and spinal SDH to discuss the features, etiology, and treatment strategy. Although surgical intervention was mainly selected for intracranial CSDH, conservative observation was mainly selected for spinal SDH. Outcomes were good in all patients. We created a new classification of spinal SDH shape using sagittal MRI. This classification indicates that cases with both ventral and dorsal SDH tend to require surgical intervention. This classification may help in deciding treatment strategies. PMID- 26996735 TI - Cerebral Infarction and Subarachnoid Hemorrhage Caused by Central Nervous System Aspergillus Infection. AB - BACKGROUND: The mortality rate of central nervous system (CNS) Aspergillus infection is >90%. Most cases with ruptured aneurysmal formation resulting from CNS aspergilloma invasion into the arterial wall are difficult to treat with surgical therapy, antifungal drugs, or steroid administration. There is no established therapy for ruptured Aspergillus aneurysms. Both a standardized examination for the diagnosis of CNS aspergillosis and effective treatment of ruptured Aspergillus aneurysms are needed. CASE DESCRIPTION: A 56-year-old man developed prolonged fever and headache. Magnetic resonance imaging showed a mass lesion around the brainstem. No laboratory data were suspicious for inflammatory diseases or autoimmune diseases. Considering the invasiveness of a surgical approach, we initiated steroid pulse therapy to confirm whether the mass would shrink before biopsy or resection for definitive pathologic diagnosis. Cerebral infarction and subarachnoid hemorrhage occurred almost concurrently just after steroid therapy. We first performed decompression surgery to treat the elevated intracranial hypertension. The specimen taken from the mass lesion at the time of surgery showed CNS Aspergillus fungal forms. Endovascular treatment of the ruptured aneurysm was performed, and medical therapy with an antifungal drug was started. After the Aspergillus infection was well controlled, the patient was discharged. Glasgow Outcome Scale score at discharge was 3. CONCLUSIONS: Although most patients with ruptured Aspergillus aneurysm have poor outcomes as reported in the literature, this patient's clinical course and outcome were good. Early recognition of CNS aspergillosis and timely surgical intervention to control the vascular event can improve the prognosis for these patients. PMID- 26996736 TI - In support of community-based emergency contraception. PMID- 26996737 TI - Postpartum contraception: An exploratory study of lactation consultants' knowledge and practices. AB - OBJECTIVE: Lactation consultants interact with women during the postpartum period; however, they may not have comprehensive education on postpartum contraception and the impact on breastfeeding. The aims of this study were to assess lactation consultants' knowledge and practices about postpartum contraception and assess whether lactation consultants are interested in more education on postpartum contraception. STUDY DESIGN: We distributed a 30-question survey to self-identified lactation consultants and recruited participants via email, social media and at the 2015 California Breastfeeding Summit. RESULTS: We surveyed a total of 194 lactation consultants. Seventy-seven percent (137/177) stated they offer advice about postpartum contraception and its impact on breastfeeding. The majority of lactation consultants felt the theoretical or proven risks outweighed the benefits or there was an unacceptable health risk for the progestin-only pill 76.3% (100/131), progestin injection 90.1% (118/131) and progestin implant 93.1% (122/131) if used within 21days of delivery. Although 68.7% (92/134) reported prior education on postpartum contraception, 82.1% (110/134) reported wanting more education on this topic, specifically in the form of a webinar 61.9% (83/134). Only 29.9% (40/134) reported knowledge of the United States Centers for Disease Control and Prevention 2011 Medical Eligibility Criteria for Contraceptive Use (USMEC) guidance for postpartum contraception. CONCLUSION: There is a disconnect between the USMEC guidance and lactation consultants' knowledge regarding the safety of immediate postpartum contraception. IMPLICATIONS: This study explores lactation consultants' knowledge and practices about postpartum contraception, demonstrating that more evidence based education is needed on this topic. PMID- 26996739 TI - Spatial and Temporal Epidemiology of Nephropathia Epidemica Incidence and Hantavirus Seroprevalence in Rodent Hosts: Identification of the Main Environmental Factors in Europe. AB - In Europe, the increasing number of nephropathia epidemica (NE) infections in humans, caused by Puumala virus carried by bank voles (Myodes glareolus), has triggered studies of environmental factors driving these infections. NE infections have been shown to occur in specific geographical areas characterized by environmental factors that influence the distribution and dynamics of host populations and virus persistence in the soil. Here, we review the influence of environmental conditions (including climate factors, food availability and habitat conditions) with respect to incidence in humans and seroprevalence in rodents, considering both direct and indirect transmission pathways. For each type of environmental factor, results and discrepancies between studies are presented and examined in the light of biological hypotheses. Overall, food availability and temperature appear to be the main drivers of host seroprevalence and NE incidence, but data quality and statistical approaches varied greatly among studies. We highlight the issues that now need to be addressed and suggest improvements for study design in regard to the current knowledge on hantavirus epidemiology. PMID- 26996738 TI - Calculating the fetal fraction for noninvasive prenatal testing based on genome wide nucleosome profiles. AB - OBJECTIVE: While large fetal copy number aberrations can generally be detected through sequencing of DNA in maternal blood, the reliability of tests depends on the fraction of DNA that originates from the fetus. Existing methods to determine this fetal fraction require additional work or are limited to male fetuses. We aimed to create a sex-independent approach without additional work. METHODS: DNA fragments used for noninvasive prenatal testing are cut only by natural processes; thus, influences on cutting by the packaging of DNA in nucleosomes will be preserved in sequencing. As cuts are expected to be made preferentially in linker regions, the shorter fetal fragments should be enriched for reads starting in nucleosome covered positions. RESULTS: We generated genome-wide nucleosome profiles based on single end sequencing of cell-free DNA. We found a difference between DNA digestion of fetal cell-free DNA and maternal cell-free DNA and used this to calculate the fraction of fetal DNA in maternal plasma for both male and female fetuses. CONCLUSION: Our method facilitates cost-effective noninvasive prenatal testing, as the fetal DNA fraction can be estimated without the need for expensive paired-end sequencing or additional tests. The methodology is implemented as a tool, which we called SANEFALCON (Single reAds Nucleosome basEd FetAL fraCtiON). It is available for academic and non-profit purposes under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License. github.com/rstraver/sanefalcon. (c) 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. PMID- 26996740 TI - Antagonistic interactions between an invasive alien and a native coccinellid species may promote coexistence. AB - Despite the capacity of invasive alien species to alter ecosystems, the mechanisms underlying their impact remain only partly understood. Invasive alien predators, for example, can significantly disrupt recipient communities by consuming prey species or acting as an intraguild predator (IGP). Behavioural interactions are key components of interspecific competition between predators, yet these are often overlooked invasion processes. Here, we show how behavioural, non-lethal IGP interactions might facilitate the establishment success of an invading alien species. We experimentally assessed changes in feeding behaviour (prey preference and consumption rate) of native UK coccinellid species (Adalia bipunctata and Coccinella septempunctata), whose populations are, respectively, declining and stable, when exposed to the invasive intraguild predator, Harmonia axyridis. Using a population dynamics model parameterized with these experimental data, we predicted how intraguild predation, accommodating interspecific behavioural interactions, might impact the abundance of the native and invasive alien species over time. When competing for the same aphid resource, the feeding rate of A. bipunctata significantly increased compared to the feeding in isolation, while the feeding rate of H. axyridis significantly decreased. This suggests that despite significant declines in the UK, A. bipunctata is a superior competitor to the intraguild predator H. axyridis. In contrast, the behaviour of non-declining C. septempunctata was unaltered by the presence of H. axyridis. Our experimental data show the differential behavioural plasticity of competing native and invasive alien predators, but do not explain A. bipunctata declines observed in the UK. Using behavioural plasticity as a parameter in a population dynamic model for A. bipunctata and H. axyridis, coexistence is predicted between the native and invasive alien following an initial period of decline in the native species. We demonstrate how empirical and theoretical techniques can be combined to understand better the processes and consequences of alien species invasions for native biodiversity. PMID- 26996741 TI - Implications of the BIA-102474-101 study for review of first-into-human clinical trials. AB - Over the past 10 years, thousands of first-into-human (FIH) clinical trials have been performed in Europe, with few severe adverse events (SAEs). Each has received detailed prior safety review at both the local clinical research facility and at national drug regulatory authority level. The recent fatal SAE in the BIA-102474-101 clinical trial shows the limitations of this process. Although criticized for not sequentially dosing subjects both within and between cohorts - as recommended by the European Medicines Agency for high-risk compounds after the TeGenero clinical trial disaster in 2006 - BIA-102474-101 was not considered to be high risk. Indeed, compounds with similar mechanisms of action had previously been taken through phase I and II trials without incident, and higher doses had been safely given for longer durations to nonhuman primates. If the available data are comprehensive and accurate, and further investigation does not reveal unreported warning signs, this study has serious implications for ongoing and future review of FIH clinical trials. All preclinical study documents and clinical data collected during the BIA-102474-101 trial should be made available urgently so that lessons can be learnt. In the meantime, reviewers and clinical researchers should always ask for information on drug and target interactions and full reports of preclinical toxicity studies, and plan sequential dosing with longer delays between patients and cohorts, particularly if late SAEs might be anticipated. The use of individual patient pharmacokinetic and dynamic data should guide sequential dosing. A process for systematic risk assessment, like that currently used in the Netherlands, should be applied routinely to all trials with novel compounds. PMID- 26996742 TI - [Generalists or specialists: An ongoing debate]. PMID- 26996743 TI - Smoking in male patients with schizophrenia in China: A meta-analysis. AB - BACKGROUND: The aim of this study was to examine the prevalence of current smoking in male patients with schizophrenia in China. METHOD: A systematic literature search was conducted from database inception until June 20, 2015 without language restrictions in PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and WanFang Database. Studies fulfilling the following criteria were included: (a) data available in male schizophrenia patients and (b) data available on current smoking status. Statistical analyses were performed with the Comprehensive Meta-Analysis program. RESULTS: A total of 23 studies met eligibility criteria for the meta-analysis. The pooled prevalence of current smoking was 59.1% (95% Confidence interval [CI]: 53.3-64.7%). Current smoking was significantly more frequent in inpatients than in outpatients (61.3% vs. 48.2%, Q=7.5, P=0.006), and higher in chronic compared to first-episode patients (74.5% vs. 45.1%, Q=32.3, P=0.0001). Furthermore, using a median split, patients aged 38.2 years or older smoked more often than those aged below 38.2 years (65.8% vs. 52.3%, Q=6.4, P=0.01). There were no significant associations between prevalence of current smoking and definitions of smoking, study publication year, sample size and illness duration. CONCLUSIONS: The pooled prevalence of current smoking of male patients with schizophrenia in China is lower compared to Western and other Asian countries. Possible relationships between lower prevalence of current smoking and psychopathology in patients with schizophrenia require further investigation. PMID- 26996744 TI - Long-term outcomes after adolescent in-patient treatment due to alcohol intoxication: A control group study. AB - BACKGROUND: The long-term psychosocial development of adolescents admitted to in patient treatment with alcohol intoxication (AIA) is largely unknown. METHODS: We invited all 1603 AIAs and 641 age- and sex-matched controls, who had been hospitalized in one of five pediatric departments between 2000 and 2007, to participate in a telephone interview. 277 cases of AIA and 116 controls (mean age 24.2 years (SD 2.2); 46% female) could be studied 5-13 years (mean 8.3, SD 2.3) after the event. The control group consisted of subjects who were admitted due to conditions other than alcohol intoxication. Blood alcohol concentration on admission was systematically measured in the AIA but, owing to the retrospective study design, not in the control group. Subtle alcohol intoxication could therefore not be entirely ruled out in the control group. Long-term outcome measures included current DSM-5 alcohol use disorders (AUD), drinking patterns, illicit substance use, regular smoking, general life satisfaction, use of mental health treatment, and delinquency. RESULTS: AIA had a significantly elevated risk to engage in problematic habitual alcohol use, to exhibit delinquent behaviors, and to use illicit substances in young adulthood compared to the control group. Severe AUD also occurred considerably more often in the AIA than the control group. CONCLUSIONS: In the majority of AIAs, further development until their mid twenties appears to be unremarkable. However, their risk to develop severe AUD and other problematic outcomes is significantly increased. This finding calls for a diagnostic instrument distinguishing between high- and low-risk AIAs already in the emergency room. PMID- 26996745 TI - Naloxone without the needle - systematic review of candidate routes for non injectable naloxone for opioid overdose reversal. AB - INTRODUCTION: Deaths from opioid overdose can be prevented through administration of the antagonist naloxone, which has been licensed for injection since the 1970s. To support wider availability of naloxone in community settings, novel non injectable naloxone formulations are being developed, suitable for emergency use by non-medical personnel. OBJECTIVES: 1) Identify candidate routes of injection free naloxone administration potentially suitable for emergency overdose reversal; 2) consider pathways for developing and evaluating novel naloxone formulations. METHODS: A three-stage analysis of candidate routes of administration was conducted: 1) assessment of all 112 routes of administration identified by FDA against exclusion criteria. 2) Scrutiny of empirical data for identified candidate routes, searching PubMed and WHO International Clinical Trials Registry Platform using search terms "naloxone AND [route of administration]". 3) Examination of routes for feasibility and against the inclusion criteria. RESULTS: Only three routes of administration met inclusion criteria: nasal, sublingual and buccal. Products are currently in development and being studied. Pharmacokinetic data exist only for nasal naloxone, for which product development is more advanced, and one concentrated nasal spray was granted licence in the US in 2015. However, buccal naloxone may also be viable and may have different characteristics. CONCLUSION: After 40 years of injection based naloxone treatment, non-injectable routes are finally being developed. Nasal naloxone has recently been approved and will soon be field-tested, buccal naloxone holds promise, and it is unclear what sublingual naloxone will contribute. Development and approval of reliable non-injectable formulations will facilitate wider naloxone provision across the community internationally. PMID- 26996747 TI - Laser-induced microstructuring of two-dimensional layered inorganic-organic perovskites. AB - Non-contact bi-directional micropatterning of two-dimensional (2D) layered inorganic-organic (IO) perovskite [(R-NH3)2PbI4, R = organic moiety] thin films by direct laser writing (DLW) has been reported. These 2D materials are in the form of natural multiple quantum well (MQW) structures and show excitonic luminescence at room temperature because of quantum and dielectric confinement effects. Systematic optical and structural analyses of these laser processed hybrid systems provide an insight into laser-matter interaction and a pathway to develop technology to define complex 2D material based devices with new functionalities. These laser-matter interaction studies reveal several concurrent processes: single photon absorption, material ablation, melting and agglomeration of nanostructures and chemical/physical modifications. This study also provides an insight into chemical and optical changes in laser processed 2D perovskites which subsequently can be recovered by chemical processing. Apart from controllable feature sizes, the prolonged laser exposure results in material agglomeration in the form of nano-pillars at the laser track boundaries. Low-cost micro/nano-scaffolding of IO perovskites may have several important advantages in scalable optoelectronic devices, the realisation of luminescent photonic architectures (photonic crystals and waveguides), and light harvesting elements for IO LEDs and solar cells. PMID- 26996746 TI - Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes. AB - Obesity and diabetes are major public health problems, and are linked to the development of heart failure. Emerging data highlight the importance of alterations in cardiac energy metabolism as a major contributor to cardiac dysfunction related to obesity and diabetes. Increased rates of fatty acid oxidation and decreased rates of glucose utilization are two prominent changes in cardiac energy metabolism that occur in obesity and diabetes. This metabolic profile is probably both a cause and consequence of a prominent cardiac insulin resistance, which is accompanied by a decrease in both cardiac function and efficiency, and by the accumulation of potentially toxic lipid metabolites in the heart that can further exaggerate insulin resistance and cardiac dysfunction. The high cardiac fatty acid oxidation rates seen in obesity and diabetes are attributable to several factors, including: 1) increased fatty acid supply and uptake into the cardiomyocyte, 2) increased transcription of fatty acid metabolic enzymes, 3) decreased allosteric control of mitochondrial fatty acid uptake and fatty acid oxidation, and 4) increased post-translational acetylation control of various fatty acid oxidative enzymes. Emerging evidence suggests that therapeutic approaches aimed at switching the balance of cardiac energy substrate preference from fatty acid oxidation to glucose use can prevent cardiac dysfunction associated with obesity and diabetes. Modulating acetylation control of fatty acid oxidative enzymes is also a potentially attractive strategy, although presently this is limited to precursors of nicotinamide adenine or nonspecific activators of deacetylation such as resveratrol. This review will focus on the metabolic alterations in the heart that occur in obesity and diabetes, as well as on the molecular mechanisms controlling these metabolic changes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 26996749 TI - Conformational Compatibility Is Essential for Heterologous Aggregation of alpha Synuclein. AB - Under aggregation-prone conditions, soluble amyloidogenic protein monomers can self-assemble into fibrils or they can fibrillize on preformed fibrillar seeds (seeded aggregation). Seeded aggregations are known to propagate the morphology of the seeds in the event of cross-seeding. However, not all proteins are known to cross-seed aggregation. Cross-seeding has been proposed to be restricted either because of differences in the protein sequences or because of conformations between the seeds and the soluble monomers. Here, we examine cross seeding efficiency between three alpha-synuclein sequences, wild-type, A30P, and A53T, each varying in only one or two amino acids but forming morphologically distinct fibrils. Results from bulk Thioflavin-T measurements, monomer incorporation quantification, single fibril fluorescence microscopy, and atomic force microscopy show that under the given solution conditions conformity between the conformation of seeds and monomers is essential for seed elongation. Moreover, elongation characteristics of the seeds are defined by the type of seed. PMID- 26996748 TI - Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise. AB - Apoptosis within cancer cells is controlled by the BCL-2 family of proteins, making them powerful arbiters of cell fate in response to stress induced by neoplastic transformation as well as exposure to anti-cancer therapies. Many cancers evade pro-apoptotic stress signals by up-regulating anti-apoptotic proteins such as BCL-2, BCL-XL or MCL-1 to maintain their survival. However, this may come at a cost, as these cancers may also become dependent on these anti apoptotic proteins for survival. The development and deployment of BCL-2 family inhibitors (drugs that mimic the activity of pro-apoptotic BH3-only proteins or 'BH3 mimetics') is based on this paradigm, and the first potent and specific molecules are now being evaluated in clinical trials. We review the recent successes in this field, the challenges currently being faced, and the promising future ahead. PMID- 26996750 TI - Does Prior Antiplatelet Treatment Increase the Risk of Hemorrhagic Transformation and Unfavorable Outcome on Day 90 after Intravenous Thrombolysis in Acute Ischemic Stroke Patients? AB - BACKGROUND: The effect of prior antiplatelet (AP) therapy on the risk of hemorrhagic transformation (HT), and on functional outcomes of acute ischemic stroke (AIS) after intravenous thrombolysis (IVT), is not known. We performed a retrospective analysis to determine whether history of AP therapy is associated with post-thrombolysis HT and poor prognosis in AIS patients. METHODS: Data pertaining to 145 patients with AIS, who underwent IVT between October 2008 and January 2015, were analyzed. The patients were divided into 2 groups based on whether or not they had received prior AP therapy. Neurological outcomes at 24 hours and 3 months after IVT therapy were assessed. Intergroup difference in cost of treatment was also evaluated. A multivariate logistic regression model was used to identify independent predictors of post-thrombolysis HT. RESULTS: Among 145 patients, 23 (15.8%) had received prior AP therapy. On multivariate analyses, older age (odds ratio [OR]: 1.084; confidence interval [CI], 1.028-1.144) and prior AP therapy (OR: 3.318; CI, 1.172-9.398) were found to be independent predictors of HT. CONCLUSION: In this study, prior AP therapy was independently associated with post-thrombolysis HT in AIS. PMID- 26996752 TI - Analysis of defect luminescence in Ga-doped ZnO nanoparticles. AB - We applied cathodoluminescence (CL) spectroscopy to evaluate the defect-induced luminescence within ZnO and Ga-doped ZnO (GZO) nanoparticles. The observed emissions from defect sites present in the GZO lattice exhibited a strong dependence on both dopant content and synthesis methods. The strong and broad defect-induced emissions and inhomogeneous population of intrinsic defects in nano-sized ZnO particles could effectively be suppressed by Ga doping, although large dopant amounts caused the generation of negatively-charged defects, VZn and Oi, with a subsequent increase of the luminescence. Upon deconvolution of the retrieved CL spectra into individual sub-bands, the physical origin of all the sub-bands could be clarified, and related to sample composition and synthesis protocol. This study lays the foundation of quantitative CL evaluation of defects to assess the quality of GZO optoelectronic devices. PMID- 26996751 TI - Erdheim-Chester Disease: An Unusual Cause of Intracranial Vasculitis and Progressive Leukoencephalopathy. AB - Erdheim-Chester disease (ECD) is a non-Langerhans histiocytosis affecting multiple organs. Stroke as symptom onset of ECD with intracranial vasculitis is unusual. We report the case of a 64-year-old man who presented with an acute ischemic stroke associated with a moderate leukoencephalopathy and intracranial arteries stenosis. Four years later, he developed movement disorders with dysarthria and cognitive impairment. Neuroradiological findings demonstrated a rapidly progressive and diffuse leukoencephalopathy associated with brain atrophy and infiltration of the intracranial vertebral artery wall. Brain postmortem evaluation confirmed the diagnosis of ECD. This diagnosis should be evoked in patients with cryptogenic stroke, progressive leukoencephalopathy, and infiltration of the arterial wall. PMID- 26996753 TI - Li(V0.5Ti0.5)S2 as a 1 V lithium intercalation electrode. AB - Graphite, the dominant anode in rechargeable lithium batteries, operates at ~ 0.1 V versus Li(+)/Li and can result in lithium plating on the graphite surface, raising safety concerns. Titanates, for example, Li4Ti5O12, intercalate lithium at ~ 1.6 V versus Li(+)/Li, avoiding problematic lithium plating at the expense of reduced cell voltage. There is interest in 1 V anodes, as this voltage is sufficiently high to avoid lithium plating while not significantly reducing cell potential. The sulfides, LiVS2 and LiTiS2, have been investigated as possible 1 V intercalation electrodes but suffer from capacity fading, large 1st cycle irreversible capacity or polarization. Here we report that the 50/50 solid solution, Li1+x(V0.5Ti0.5)S2, delivers a reversible capacity to store charge of 220 mAhg(-1) (at 0.9 V), 99% of theoretical, at a rate of C/2, retaining 205 mAhg(-1) at C-rate (92% of theoretical). Rate capability is excellent with 200 mAhg(-1) at 3C. C-rate is discharge in 1 h. Polarization is low, 100 mV at C/2. To the best of our knowledge, the properties/performances of Li(V0.5Ti0.5)S2 exceed all previous 1 V electrodes. PMID- 26996754 TI - Characteristics of rumen in Naemi lamb: Morphological changes in response to altered feeding regimen. AB - This study sought to chart the ontogenesis of rumen in Naemi lambs through histomorphometeric evaluation subjected to alfalfa hay in total mixed rations (TMR). A total of 40 growing healthy Naemi male lambs (28.85+/-1.09kg), at weaning (90+/-3days) was randomly distributed into four groups. One group was fed on TMR (control) only, while others were supplemented with restricted amount of alfalfa hay at the rate of 100g per day (T1), 200g once per two days (T2) and 300g once per three days (T3) in addition to ad libitum TMR. The results indicated that body weight and dry matter intake increased significantly in treated groups. Significantly higher (P<0.05) pH was recorded in all the treated groups after 8h of feeding. Similarly, the brightness (L*), redness (a*) and yellowness ((b*) of rumen was significantly higher (P<0.05) in treated groups. The papillary length, width and surface area of rumen were significantly (P<0.05) high in alfalfa supplemented groups. Iron (Fe) concentration in rumen tissue decreased significantly (P<0.05) in treated groups. We concluded that a dietary plan based on ad libitum TMR with the addition of alfalfa at the rate of aforementioned protocol not only enhanced feed intake and growth rate of the growing Naemi lambs but also improved the structural characteristics of the rumen. PMID- 26996755 TI - Simulation of early calcific aortic valve disease in a 3D platform: A role for myofibroblast differentiation. AB - PURPOSE: Calcific aortic valve disease (CAVD) is the most prevalent valve disease in the Western world. Recent difficulty in translating experimental results on statins to beneficial clinical effects warrants the need for understanding the role of valvular interstitial cells (VICs) in CAVD. In two-dimensional culture conditions, VICs undergo spontaneous activation similar to pathological differentiation, which intrinsically limits the use of in vitro models to study CAVD. Here, we hypothesized that a three-dimensional (3D) culture system based on naturally derived extracellular matrix polymers, mimicking the microenvironment of native valve tissue, could serve as a physiologically relevant platform to study the osteogenic differentiation of VICs. PRINCIPAL RESULTS: Aortic VICs loaded into 3D hydrogel constructs maintained a quiescent phenotype, similar to healthy human valves. In contrast, osteogenic environment induced an initial myofibroblast differentiation (hallmarked by increased alpha smooth muscle actin [alpha-SMA] expression), followed by an osteoblastic differentiation, characterized by elevated Runx2 expression, and subsequent calcific nodule formation recapitulating CAVD conditions. Silencing of alpha-SMA under osteogenic conditions diminished VIC osteoblast-like differentiation and calcification, indicating that a VIC myofibroblast-like phenotype may precede osteogenic differentiation in CAVD. MAJOR CONCLUSIONS: Using a 3D hydrogel model, we simulated events that occur during early CAVD in vivo and provided a platform to investigate mechanisms of CAVD. Differentiation of valvular interstitial cells to myofibroblasts was a key mechanistic step in the process of early mineralization. This novel approach can provide important insight into valve pathobiology and serve as a promising tool for drug screening. PMID- 26996758 TI - Influence of enamel matrix derivative on healing of root surfaces after bonding treatment and intentional replantation of vertically fractured roots. AB - BACKGROUND/AIM: The objectives of this study were to histopathologically evaluate cementum regeneration on root surfaces when an enamel matrix derivative (EMD) was used to bond a vertically fractured root and to evaluate the effectiveness of EMD in inhibiting root resorption. MATERIAL AND METHODS: A total of 40 roots from 24 maxillary premolars in beagles were used. The root was vertically fractured using a chisel and mallet. Super-Bond was then used to bond the fractured root. In the experimental group, the root surface was treated with ethylenediaminetetraacetic acid and an EMD. The control group received no treatment. The root was then replanted in its original location. Histopathological observation and measurement using image-analyzing software were carried out after 8 weeks. RESULTS: In the experimental group, shallow resorption cavities developed on the root planed surfaces with new acellular cementum appearing over them. In the control group, no new cementum was seen on the planed surfaces, and there was connective tissue joining the roots. In some of the samples, resorption and multinucleated giant cells were seen. The experimental group showed a significantly larger volume of cementum formation (P < 0.001), and the volume of root resorption was significantly smaller (P = 0.004). CONCLUSION: When bonding and replanting tooth roots after a vertical fracture, the application of EMD was effective in regenerating cementum on root surfaces from which periodontal ligament had been lost in the area around the fracture line and in reducing the incidence of root resorption. PMID- 26996757 TI - Mast cells promote proliferation and migration and inhibit differentiation of mesenchymal stem cells through PDGF. AB - BACKGROUND: Mast cells (MCs) dynamically participate in wound healing after myocardial infarction (MI) by releasing cytokines. Indeed, MC-deficient mice undergo rapid left ventricular dilation post-MI. Mesenchymal stem cells (MSCs) are recruited to the injured region following an MI and have potential for cardiac repair. In the current study, we evaluate the effect of MCs on MSC proliferation and myogenic differentiation. METHODS AND RESULTS: MCs were cultured from mouse bone marrow and MC granulate (MCG) was extracted from MCs via freeze-thaw cycles followed by filtration. alpha-SMA (smooth muscle actin) expression was examined as an indicator of myogenic differentiation. MSC/MC co culture resulted in decreased MSC differentiation indicated by alpha-SMA suppression in MSCs. MCG also suppressed alpha-SMA expression and increased MSC migration and proliferation in a dose-dependent manner. Removal of MCG rescued alpha-SMA expression and MSC differentiation. Platelet derived growth factor (PDGF) receptor blockade using AG1296 also rescued MSC differentiation even after MCG treatment. Real-time PCR and Western blot showed that MCG exerted its effects on MSCs via downregulation of miR-145 and miR-143, downregulation of myocardin, upregulation of Klf4, and increased Erk and Elk1 phosphorylation. CONCLUSIONS: MCs promote MSC proliferation and migration by suppressing their myogenic differentiation. MCs accomplish this via activation of the PDGF pathway, downregulation of miR-145/143, and modulation of the myocardin-Klf4 axis. These data suggest a potential role for MSC/MC interaction in the infarcted heart where MCs may inhibit MSCs from differentiation and promote their proliferation whereby increased cardiac MSC accumulation promotes eventual cardiac regeneration after MCs cease activity. PMID- 26996759 TI - Validation of the World Health Organization Disability Assessment Schedule (WHO DAS II) in Greek and its added value to the Short Form 36 (SF-36) in a sample of people with or without disabilities. AB - BACKGROUND: There is controversy and ongoing interest on the measurement of functionality in the personal and social level. OBJECTIVES: (1) to validate the Greek version of the World Health Organization Disability Assessment Schedule (WHO DAS II) and (2) to determine its added value to the physical and psychological health subscales of the Short Form 36 (SF-36). METHODS: In a cross sectional design, data were collected between December 2014 and March 2015 by using three questionnaires (WHO DAS II, SF-36, PSS-14) in a sample of people with disabilities (n = 101) and without disabilities (n = 109) in Athens, Greece. WHO DAS II internal consistency, construct and criterion-related validity were assessed by Cronbach alpha, exploratory factor analysis and correlations; its added value by multivariable linear regression. RESULTS: Cronbach Alpha's were satisfactory for the WHO DAS II, PSS-14 and SF-36 (0.85, 0.88 and 0.96 respectively). Exploratory factor analysis confirmed the existence of one or two factors in people with or without disabilities, respectively. WHO DAS II score showed significant negative correlation with the physical and mental health scale of SF-36 score, especially strong for physical health while was positively related to PSS-14 score. In multivariate analysis mental health appraisal was related to perceived stress in both groups. CONCLUSIONS: This study support the validity of the Greek version of WHO DAS II and warranted its use in assessment and follow up of people with disabilities, contributing to the development of suitable policies to cover their needs and providing comparable data with other surveys using the same instrument. PMID- 26996756 TI - Myocyte-fibroblast communication in cardiac fibrosis and arrhythmias: Mechanisms and model systems. AB - Development of cardiac fibrosis and arrhythmias is controlled by the activity of and communication between cardiomyocytes and fibroblasts in the heart. Myocyte fibroblast interactions occur via both direct and indirect means including paracrine mediators, extracellular matrix interactions, electrical modulators, mechanical junctions, and membrane nanotubes. In the diseased heart, cardiomyocyte and fibroblast ratios and activity, and thus myocyte-fibroblast interactions, change and are thought to contribute to the course of disease including development of fibrosis and arrhythmogenic activity. Fibroblasts have a developing role in modulating cardiomyocyte electrical and hypertrophic activity, however gaps in knowledge regarding these interactions still exist. Research in this field has necessitated the development of unique approaches to isolate and control myocyte-fibroblast interactions. Numerous methods for 2D and 3D co culture systems have been developed, while a growing part of this field is in the use of better tools for in vivo systems including cardiomyocyte and fibroblast specific Cre mouse lines for cell type specific genetic ablation. This review will focus on (i) mechanisms of myocyte-fibroblast communication and their effects on disease features such as cardiac fibrosis and arrhythmias as well as (ii) methods being used and currently developed in this field. PMID- 26996760 TI - Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke. AB - BACKGROUND: Stroke is one of the leading causes of disability worldwide. Functional impairment, resulting in poor performance in activities of daily living (ADLs) among stroke survivors is common. Current rehabilitation approaches have limited effectiveness in improving ADL performance, function, muscle strength and cognitive abilities (including spatial neglect) after stroke, but a possible adjunct to stroke rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve ADL performance, arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke. OBJECTIVES: To assess the effects of tDCS on ADLs, arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library; 2015, Issue 2), MEDLINE (1948 to February 2015), EMBASE (1980 to February 2015), CINAHL (1982 to February 2015), AMED (1985 to February 2015), Science Citation Index (1899 to February 2015) and four additional databases. In an effort to identify further published, unpublished and ongoing trials, we searched trials registers and reference lists, handsearched conference proceedings and contacted authors and equipment manufacturers. SELECTION CRITERIA: This is the update of an existing review. In the previous version of this review we focused on the effects of tDCS on ADLs and function. In this update, we broadened our inclusion criteria to compare any kind of active tDCS for improving ADLs, function, muscle strength and cognitive abilities (including spatial neglect) versus any kind of placebo or control intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and risk of bias (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. MAIN RESULTS: We included 32 studies involving a total of 748 participants aged above 18 with acute, postacute or chronic ischaemic or haemorrhagic stroke. We also identified 55 ongoing studies. The risk of bias did not differ substantially for different comparisons and outcomes.We found nine studies with 396 participants examining the effects of tDCS versus sham tDCS (or any other passive intervention) on our primary outcome measure, ADLs after stroke. We found evidence of effect regarding ADL performance at the end of the intervention period (standardised mean difference (SMD) 0.24, 95% confidence interval (CI) 0.03 to 0.44; inverse variance method with random-effects model; moderate quality evidence). Six studies with 269 participants assessed the effects of tDCS on ADLs at the end of follow-up, and found improved ADL performance (SMD 0.31, 95% CI 0.01 to 0.62; inverse variance method with random-effects model; moderate quality evidence). However, the results did not persist in a sensitivity analysis including only trials of good methodological quality.One of our secondary outcome measures was upper extremity function: 12 trials with a total of 431 participants measured upper extremity function at the end of the intervention period, revealing no evidence of an effect in favour of tDCS (SMD 0.01, 95% CI -0.48 to 0.50 for studies presenting absolute values (low quality evidence) and SMD 0.32, 95% CI 0.51 to 1.15 (low quality evidence) for studies presenting change values; inverse variance method with random-effects model). Regarding the effects of tDCS on upper extremity function at the end of follow-up, we identified four studies with a total of 187 participants (absolute values) that showed no evidence of an effect (SMD 0.01, 95% CI -0.48 to 0.50; inverse variance method with random effects model; low quality evidence). Ten studies with 313 participants reported outcome data for muscle strength at the end of the intervention period, but in the corresponding meta-analysis there was no evidence of an effect. Three studies with 156 participants reported outcome data on muscle strength at follow-up, but there was no evidence of an effect.In six of 23 studies (26%), dropouts, adverse events or deaths that occurred during the intervention period were reported, and the proportions of dropouts and adverse events were comparable between groups (risk difference (RD) 0.01, 95% CI -0.02 to 0.03; Mantel-Haenszel method with random-effects model; low quality evidence; analysis based only on studies that reported either on dropouts, or on adverse events, or on both). However, this effect may be underestimated due to reporting bias. AUTHORS' CONCLUSIONS: At the moment, evidence of very low to moderate quality is available on the effectiveness of tDCS (anodal/cathodal/dual) versus control (sham/any other intervention) for improving ADL performance after stroke. However, there are many ongoing randomised trials that could change the quality of evidence in the future. Future studies should particularly engage those who may benefit most from tDCS after stroke and in the effects of tDCS on upper and lower limb function, muscle strength and cognitive abilities (including spatial neglect). Dropouts and adverse events should be routinely monitored and presented as secondary outcomes. They should also address methodological issues by adhering to the Consolidated Standards of Reporting Trials (CONSORT) statement. PMID- 26996761 TI - Serum Bilirubin and Their Association With C-Reactive Protein in Patients With Migraine. AB - BACKGROUND: Increased levels of C-reactive protein (CRP) have been considered as a marker in assessing neurogenic inflammation of migraine patients. An inverse relationship between serum bilirubin and CRP has been observed in various diseases. Therefore, we analyzed serum bilirubin levels in migraine patients, and investigated the relationship between serum bilirubin and CRP in migraineurs. METHODS: A total of 86 newly diagnosed migraine patients were consecutively recruited to this study. RESULTS: Significantly lower median serum total bilirubin, conjugated bilirubin (CB) and unconjugated bilirubin were found in patients with migraine than healthy controls, and the levels of CRP were significantly higher in migraine patients than healthy controls. A negative correlation between CRP and CB was observed in patients with migraine (r = 0.255, P = 0.018). In a multiple linear regression model, the concentrations of CRP remained negatively correlated with CB. CONCLUSIONS: Our study demonstrates that serum bilirubin concentrations are decreased in migraineurs, and CB levels were found to be positively correlated with CRP in migraine patents. However, larger cross-sectional and prospective studies are needed to establish whether serum bilirubin may be a useful biomarker for assessing neurogenic inflammation in migraine patients and eventually guiding the therapy. PMID- 26996762 TI - Discriminative power of Campylobacter phenotypic and genotypic typing methods. AB - The aim of this study was to compare different typing methods, individually and combined, for use in the monitoring of Campylobacter in food. Campylobacter jejuni (n=94) and Campylobacter coli (n=52) isolated from different broiler meat carcasses were characterized using multilocus sequence typing (MLST), flagellin gene A restriction fragment length polymorphism typing (flaA-RFLP), antimicrobial resistance profiling (AMRp), the presence/absence of 5 putative virulence genes; and, exclusively for C. jejuni, the determination of lipooligosaccharide (LOS) class. Discriminatory power was calculated by the Simpson's index of diversity (SID) and the congruence was measured by the adjusted Rand index and adjusted Wallace coefficient. MLST was individually the most discriminative typing method for both C. jejuni (SID=0.981) and C. coli (SID=0.957). The most discriminative combination with a SID of 0.992 for both C. jejuni and C. coli was obtained by combining MLST with flaA-RFLP. The combination of MLST with flaA-RFLP is an easy and feasible typing method for short-term monitoring of Campylobacter in broiler meat carcass. PMID- 26996764 TI - Polar alicyclic rings: synthesis and structure of all cis-1,2,3,4 tetrafluorocyclopentane. AB - The all-cis isomer of 1,2,3,4-tetrafluorocyclopentane is prepared and characterised by NMR and X-ray crystallography and the experimental structure compared with theory. The structure has a similarly high polarity to all-cis tetrafluorocyclohexanes despite the increased conformational flexibility of a cyclopentane. PMID- 26996763 TI - Ancient DNA reveals selection acting on genes associated with hypoxia response in pre-Columbian Peruvian Highlanders in the last 8500 years. AB - Archaeological evidence shows that humans began living in the high altitude Andes approximately 12,000 years ago. Andean highlanders are known to have developed the most complex societies of pre-Columbian South America despite challenges to their health and reproductive success resulting from chronic exposure to hypoxia. While the physiological adaptations to this environmental stressor are well studied in contemporary Andean highlanders, the molecular evolutionary processes associated with such adaptations remain unclear. We aim to better understand how humans managed to demographically establish in this harsh environment by addressing a central question: did exposure to hypoxia drive adaptation via natural selection within Andean populations or did an existing phenotype- characterized by reduced susceptibility to hypoxic stress--enable human settlement of the Andes? We genotyped three variable loci within the NOS3 and EGLN1 genes previously associated with adaptation to high altitude in 150 ancient human DNA samples from Peruvian high altitude and coastal low altitude sites in a time frame between ~8500-560 BP. We compare the data of 109 successful samples to forward simulations of genetic drift with natural selection and find that selection, rather than drift, explains the gradual frequency changes observed in the highland populations for two of the three SNPs. PMID- 26996765 TI - Functional Redundancy-Induced Stability of Gut Microbiota Subjected to Disturbance. AB - The microbiota should be considered as just another component of the human epigenetic landscape. Thus, health is also a reflection of the diversity and composition of gut microbiota and its metabolic status. In defining host health, it remains unclear whether diversity is paramount, or whether greater weight is held by gut microbiota composition or mono- or multiple-functional capacity of the different taxa and the mechanisms involved. A network-biology approach may shed light on the key gut players acting to protect against, or promote, disorders or diseases. This could be achieved by integrating data on total and active species, proteins and molecules, and their association with host response. In this review, we discuss the utilization of top-down and bottom-up approaches, following a functional hierarchy perspective. PMID- 26996766 TI - Oscillospira: a Central, Enigmatic Component of the Human Gut Microbiota. AB - Oscillospira is an enigmatic bacterial genus that has never been cultured, but is constantly detected by 16S rRNA gene surveys of the human microbiome. Here we summarize recent evidence that Oscillospira is positively associated with leanness and health, speculate about its physiology, and argue its potential importance for human health. PMID- 26996767 TI - Health Care Utilization and Expenditures Associated With Remote Monitoring in Patients With Implantable Cardiac Devices. AB - Several randomized trials and decision analysis models have found that remote monitoring may reduce health care utilization and expenditures in patients with cardiac implantable electronic devices (CIEDs), compared with in-office monitoring. However, little is known about the generalizability of these findings to unselected populations in clinical practice. To compare health care utilization and expenditures associated with remote monitoring and in-office monitoring in patients with CIEDs, we used Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases. We selected patients newly implanted with an implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy defibrillator (CRT-D), or permanent pacemaker (PPM), in 2009, who had continuous health plan enrollment 2 years after implantation. Generalized linear models and propensity score matching were used to adjust for confounders and estimate differences in health care utilization and expenditures in patients with remote or in-office monitoring. We identified 1,127; 427; and 1,295 pairs of patients with a similar propensity for receiving an ICD, CRT-D, or PPM, respectively. Remotely monitored patients with ICDs experienced fewer emergency department visits resulting in discharge (p = 0.050). Remote monitoring was associated with lower health care expenditures in office visits among patients with PPMs (p = 0.025) and CRT-Ds (p = 0.006) and lower total inpatient and outpatient expenditures in patients with ICDs (p <0.0001). In conclusion, remote monitoring of patients with CIEDs may be associated with reductions in health care utilization and expenditures compared with exclusive in-office care. PMID- 26996768 TI - Aortic Regurgitation in Patients Undergoing Transcatheter Aortic Valve Replacement With the Self-Expanding CoreValve Versus the Balloon-Expandable SAPIEN XT Valve. AB - The incidence of aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) in a self-expanding and a balloon-expandable system is controversial. This study aimed to examine the incidence and severity of post TAVR AR with the CoreValve (CV) versus the Edwards XT Valve (XT). Baseline, procedural, and postprocedural inhospital outcomes were compared. The primary end point was the incidence of post-TAVR AR of any severity, assessed with a transthoracic echocardiogram, in the CV versus XT groups. A multivariate logistic regression analysis was completed to evaluate for correlates of the primary end point. The secondary end points included the change in severity of AR at 30-day and 1-year follow-up. A total of 223 consecutive patients (53% men, mean age 82 years) who had transfemoral TAVR with either a CV (n = 119) or XT (n = 104) were evaluated. The rates of post-TAVR AR in the groups were similar, and there was no evidence of more-than-moderate AR in either group. There were significant differences in the rates of intraprocedural balloon postdilation with the CV (17.1%) versus XT valve (5.8%; p = 0.009) and in the rates of intraprocedural implantation of a second valve-in-valve prosthesis with the CV (9.9%) versus XT valve (2.2%; p = 0.036). There were no significant differences in inhospital safety outcomes between the 2 groups. In conclusion, the incidence of post-TAVR AR is similar between the CV and the XT valve when performed by experienced operators using optimal intraprocedural strategies, as deemed appropriate, to mitigate the severity of AR. PMID- 26996770 TI - Controlling embedment and surface chemistry of nanoclusters in metal-organic frameworks. AB - A combined theoretical and experimental approach demonstrates that nanocluster embedment into the pores of metal-organic frameworks (MOF) may be influenced by the chemical functionalisation of the MOF. Furthermore, this results in the surface functionalisation of the embedded nanoclusters, highlighting the potential of MOF scaffolds for the design and synthesis of novel functional materials. PMID- 26996769 TI - Prognostic Utility of Calcium Scoring as an Adjunct to Stress Myocardial Perfusion Scintigraphy in End-Stage Renal Disease. AB - Coronary artery calcium score (CACS) is a strong predictor of adverse cardiovascular events in the general population. Recent data confirm the prognostic utility of single-photon emission computed tomographic (SPECT) imaging in end-stage renal disease, but whether performing CACS as part of hybrid imaging improves risk prediction in this population is unclear. Consecutive patients (n = 284) were identified after referral to a university hospital for cardiovascular risk stratification in assessment for renal transplantation. Participants underwent technetium-99m SPECT imaging after exercise or standard adenosine stress in those unable to achieve 85% maximal heart rate; multislice CACS was also performed (Siemens Symbia T16, Siemens, Erlangen, Germany). Subjects with known coronary artery disease (n = 88) and those who underwent early revascularization (n = 2) were excluded. The primary outcome was a composite of death or first myocardial infarction. An abnormal SPECT perfusion result was seen in 22% (43 of 194) of subjects, whereas 45% (87 of 194) had at least moderate CACS (>100 U). The frequency of abnormal perfusion (summed stress score >=4) increased with increasing CACS severity (p = 0.049). There were a total of 15 events (8 deaths, and 7 myocardial infarctions) after a median duration of 18 months (maximum follow-up 3.4 years). Univariate analysis showed diabetes mellitus (Hazard ratio [HR] 3.30, 95% CI 1.14 to 9.54; p = 0.028), abnormal perfusion on SPECT (HR 5.32, 95% CI 1.84 to 15.35; p = 0.002), and moderate-to severe CACS (HR 3.55, 95% CI 1.11 to 11.35; p = 0.032) were all associated with the primary outcome. In a multivariate model, abnormal perfusion on SPECT (HR 4.18, 95% CI 1.43 to 12.27; p = 0.009), but not moderate-to-severe CACS (HR 2.50, 95% CI 0.76 to 8.20; p = 0.130), independently predicted all-cause death or myocardial infarction. The prognostic value of CACS was not incremental to clinical and SPECT perfusion data (global chi-square change = 2.52, p = 0.112). In conclusion, a perfusion defect on SPECT is an independent predictor of adverse outcome in potential renal transplant candidates regardless of the CACS. The use of CACS as an adjunct to SPECT perfusion data does not provide incremental prognostic utility for the prediction of mortality and nonfatal myocardial infarction in end-stage renal disease. PMID- 26996772 TI - Heterogeneous Rhodium-Catalyzed Aerobic Oxidative Dehydrogenative Cross-Coupling: Nonsymmetrical Biaryl Amines. AB - The first heterogeneously catalyzed oxidative dehydrogenative cross-coupling of aryl amines is reported herein. 2-Naphthylamine analogues were reacted with various electron-rich arenes using a heterogeneous Rh/C catalyst under mild aerobic conditions, thus affording nonsymmetrical biaryl amines in excellent yields with high selectivities. This reaction provides a mild, operationally simple, and efficient approach for the synthesis of biaryls which are important to pharmaceutical and materials chemistry. PMID- 26996771 TI - Radiological and Biological Assessment of Immediately Restored Anterior Maxillary Implants Combined with GBR and Free Connective Tissue Graft. AB - OBJECTIVES: Radiologic and biologic assessment of immediately restored Implants combined with guided bone regeneration (GBR) and free connective tissue graft. METHODS: 1-4 year retrospective study involving 34 patients treated with maxillary immediately restored anterior single-implants. Soft tissue dimensions, radiographic bone loss, and biological and prosthetic complications were assessed. RESULTS: During the mean follow up period of 29 months the study group presented a mean mesial bone loss of 1.10 +/- 0.39 mm (range: 0.5-2.4 mm), and mean distal bone loss of 1.19 +/- 0.41 mm (range: 0.4-2.1 mm). Mean periimplant probing depth of 3.49 mm (SD +/- 1.06) and 2.35 (SD +/- 0.52) for the contralateral tooth (highly significant p < 0.001). Bleeding on probing was present in 29.4% of the examined implant supported crown sites and 10.4% of the contralateral teeth (p < 0.001). CONCLUSIONS: Anterior maxillary single-tooth replacement, using GBR and connective tissue graft according to the concept of immediate implant placement, and non-functional restoration is an accepted treatment modality achieving favorable peri-implant soft tissue condition. PMID- 26996773 TI - Pectin as an Extraordinary Natural Kinetic Hydrate Inhibitor. AB - Pectin as a novel natural kinetic hydrate inhibitor, expected to be eco-friendly and sufficiently biodegradable, was studied in this paper. The novel crystal growth inhibition (CGI) and standard induction time methods were used to evaluate its effect as hydrate inhibitor. It could successfully inhibit methane hydrate formation at subcooling temperature up to 12.5 degrees C and dramatically slowed the hydrate crystal growth. The dosage of pectin decreased by 66% and effective time extended 10 times than typical kinetic inhibitor. Besides, its maximum growth rate was no more than 2.0%/h, which was far less than 5.5%/h of growth rate for PVCap at the same dosage. The most prominent feature was that it totally inhibited methane hydrate crystal rapid growth when hydrate crystalline occurred. Moreover, in terms of typical natural inhibitors, the inhibition activity of pectin increased 10.0-fold in induction time and 2.5-fold in subcooling temperature. The extraordinary inhibition activity is closely related to its hydrogen bonding interaction with water molecules and the hydrophilic structure. Finally, the biodegradability and economical efficiency of pectin were also taken into consideration. The results showed the biodegradability improved 75.0% and the cost reduced by more than 73.3% compared to typical commercial kinetic inhibitors. PMID- 26996774 TI - Unexpected Stealing From the Heart. AB - BACKGROUND: Coronary subclavian steal syndrome (CSSS) is defined as retrograde flow in the internal mammary artery graft, after coronary artery bypass surgery, resulting in anterior wall myocardial ischemia. If undiagnosed, it may lead to significant infarction. Its incidence has been under-reported. CASE REPORT: A 74 year-old woman presented with sudden onset of typical angina, which was associated with dyspnea, nausea, and vomiting. Her medical history was significant for coronary artery disease, with prior coronary artery bypass surgery (CABG), chronic obstructive pulmonary disease (COPD), hypertension, diabetes type 2, dyslipidemia, hypothyroidism, and depression. Physical examination demonstrated a weak left radial pulse, and a differential blood pressure reading in her arms. She developed massive hematochezia that resulted in electrocardiogram changes: ST segment depression in the inferior and lateral leads with isolated ST segment elevation of aVR. Cardiac catheterization demonstrated retrograde flow through the left internal mammary artery (LIMA), resulting in CSSS. CONCLUSIONS: This case highlights the diagnostic challenge of CSSS as the underlying etiology for ischemia in a patient with remote coronary artery bypass surgery (CABG). It underscores the importance of thorough physical examination in patients who are at high risk for coronary atherosclerosis and remote complications after CABG. It also highlights optimal strategies for management of CSSS with percutaneous transluminal angioplasty. PMID- 26996775 TI - Up-front neck dissection followed by definitive (chemo)-radiotherapy in head and neck squamous cell carcinoma: Rationale, complications, toxicity rates, and oncological outcomes - A systematic review. AB - BACKGROUND AND PURPOSE: Lymph node metastases of head and neck cancer are considered one of the most negative prognostic factors. While outcomes and feasibility of chemo-radiotherapy ((C)RT) with or without adjuvant planned neck dissection (ND) in organ-preservation treatment strategy have been addressed, the role of ND before (C)RT, called up-front neck dissection (UFND), is not clearly established. This review provides a critical appraisal of UFND. MATERIAL AND METHODS: Articles were identified with a systematic approach. Outcomes included post-UFND delay of (C)RT, surgical complications, radiation toxicity and oncologic outcome. RESULTS: Fifteen studies met inclusion criteria, totaling 607 patients undergoing UFND. Part of the data suggest advantages toward less surgical complications compared with salvage ND, decreased serious acute radiation toxicity and better oncological outcomes when compared with (C)RT alone. The overall heterogeneity of the analyzed data does not allow a meta analysis that provides high-quality evidence in favor or against UFND. CONCLUSIONS: Due to lack of well-designed randomized trials, it is difficult to assess the role of UFND in organ-preserving (C)RT setting of head and neck cancer. PMID- 26996776 TI - Hair dye use, regular exercise, and the risk and prognosis of prostate cancer: multicenter case-control and case-only studies. AB - BACKGROUND: This study investigated the effects that hair dye use and regular exercise exert on the risk and prognosis of prostate cancer. METHODS: We studied 296 cases of histologically confirmed prostate cancer and 296 age- (in 2-y bands), ethnicity-, and hospital-matched controls in Taiwan between August 2000 and December 2008. To determine the rate of prostate cancer survival, another 608 incident prostate cancer cases occurring between August 2000 and December 2007 were investigated. Information on hair dye use and regular exercise was obtained using a standardized questionnaire. RESULTS: The use of hair dyes was associated with a significant 2.15-fold odds of developing prostate cancer (adjusted odds ratio = 2.15, 95% confidence interval [CI] = 1.32-3.57), but was not associated with prostate cancer survival, compared with no use. The significant risks were more prominent in users aged < 60 years who had used hair dyes for > 10 years, > 6 times per year, and started using hair dyes before 1980. By contrast, regular exercise significantly reduced the number of prostate-cancer-specific death (adjusted hazard ratio = 0.37, 95% CI = 0.16-0.83); the protective effect of exercise was more prominent among cancer patients who exercised daily (>= 7 times/week). However, exercise could not prevent the development of prostate cancer. CONCLUSIONS: Hair dye use increased the risk of prostate cancer, whereas regular exercise reduced the number of prostate-cancer-specific deaths. PMID- 26996777 TI - Diagnostic potential of PET/CT using a 68Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience. AB - PURPOSE: To evaluate the diagnostic potential of whole-body PET/CT using a 68Ga labelled PSMA ligand in renal cell carcinoma (RCC). METHODS: Six patients with histopathologically proven RCC underwent 68Ga-PSMA PET/CT. Each PET/CT scan was evaluated in relation to lesion count, location and dignity. SUVmax was measured in primary tumours and PET-positive metastases. Tumour-to-background SUVmax ratios (TBRSUVmax) were calculated for primary RCCs in relation to the surrounding normal renal parenchyma. Metastasis-to-background SUVmax ratios (MBRSUVmax) were calculated for PET-positive metastases in relation to gluteal muscle. RESULTS: Five primary RCCs and 16 metastases were evaluated. The mean SUVmax of the primary RCCs was 9.9 +/- 9.2 (range 1.7 - 27.2). Due to high uptake in the surrounding renal parenchyma, the mean TBRSUVmax of the primary RCCs was only 0.2 +/- 0.3 (range 0.02 - 0.7). Eight metastases showed focal 68Ga-PSMA uptake (SUVmax 9.9 +/- 8.3, range 3.4 - 25.6). The mean MBRSUVmax of these PET positive metastases was 11.7 +/- 0.2 (range 4.4 - 28.1). All PET-negative metastases were subcentimetre lung metastases. CONCLUSION: 68Ga-PSMA PET/CT appears to be a promising method for detecting RCC metastases. However, no additional diagnostic value in assessing the primary tumour was found. PMID- 26996779 TI - PET/CT comparing (68)Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma. AB - PURPOSE: Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). (68)Ga-DOTA(0)-Tyr(3) octreotate ((68)Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of (68)Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. METHODS: This prospective study included 22 patients (15 men, 7 women; aged 50.0 +/- 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent (68)Ga-DOTATATE, (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional (18)F fluorodihydroxyphenylalanine ((18)F-FDOPA) PET/CT scan and only 11 patients underwent an additional (18)F-fluorodopamine ((18)F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. RESULTS: (68)Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). (18)F-FDG PET/CT, (18)F FDOPA PET/CT, (18)F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %); p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively. CONCLUSION: The results of this study demonstrate the superiority of (68)Ga DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. PMID- 26996781 TI - Generalized energy failure criterion. AB - Discovering a generalized criterion that can predict the mechanical failure of various different structural materials is one of ultimate goals for scientists in both material and mechanics communities. Since the first study on the failure criterion of materials by Galileo, about three centuries have passed. Now we eventually find the "generalized energy criterion", as presented here, which appears to be one universal law for various different kinds of materials. The validity of the energy criterion for quantitatively predicting the failure is experimentally confirmed using a metallic glass. The generalized energy criterion reveals the competition and interaction between shear and cleavage, the two fundamental inherent failure mechanisms, and thus provides new physical insights into the failure prediction of materials and structural components. PMID- 26996778 TI - Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm. AB - PURPOSE: The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [(18)F]THK5317 (also known as (S)-[(18)F]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition. METHODS: Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [(18)F]THK5317, [(11)C] Pittsburgh compound B ([(11)C]PIB), and [(18)F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [(11)C]PIB-positive (n = 11) and MCI [(11)C]PIB-negative (n = 2) groups. RESULTS: Test-retest variability for [(18)F]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [(11)C]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [(18)F]THK5317 retention than healthy controls (p = 0.002 and p = 0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [(18)F]THK5317 retention and [(18)F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [(18)F]THK5317 and [(11)C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [(11)C]PIB but high [(18)F]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients. CONCLUSIONS: The tau-specific PET tracer [(18)F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition. PMID- 26996780 TI - Adherence to health regimens among frequent attenders of Finnish healthcare. AB - OBJECTIVES: The aim of the study was to describe adherence to health regimens and the factors associated with it among adult frequent attenders (FAs). DESIGN: This was a cross-sectional study. The study sample consisted of 462 healthcare FAs in 7 municipal health centres in northern Finland. An FA is a person who has had 8 or more outpatient visits to a GP (in a health centre) or 4 or more outpatient visits to a university hospital during 1 year. The main outcome was self-reported adherence to health regimens. RESULTS: Of the FAs, 82% adhered well to their health regimens. Carrying out self-care, medical care and feeling responsible for self-care were the most significant predictors to good adherence in all models. No significant differences in adherence were found in male and female subjects, age groups or educational levels. Support from healthcare providers and support from relatives were not significant predictors of good adherence. CONCLUSION: FAs in Finland adhere well to health regimens and exceptionally well to medication. Variables that predict the best adherence of FAs to health regimens are carrying out self-care, receiving medical care and feeling responsible for self-care. PMID- 26996783 TI - Editorial: Pulmonary Delivery of Systemic Drugs- from Aerosol Generation to Efficacious Delivery. PMID- 26996782 TI - TGF-beta receptor type II costameric localization in cardiomyocytes and host cell TGF-beta response is disrupted by Trypanosoma cruzi infection. AB - Transforming growth factor beta (TGF-beta) cytokine is involved in Chagas disease establishment and progression. Since Trypanosoma cruzi can modulate host cell receptors, we analysed the TGF-beta receptor type II (TbetaRII) expression and distribution during T. cruzi - cardiomyocyte interaction. TbetaRII immunofluorescent staining revealed a striated organization in cardiomyocytes, which was co-localized with vinculin costameres and enhanced (38%) after TGF-beta treatment. Cytochalasin D induced a decrease of 45.3% in the ratio of cardiomyocytes presenting TbetaRII striations, demonstrating an association of TbetaRII with the cytoskeleton. Western blot analysis showed that cytochalasin D significantly inhibited Smad 2 phosphorylation and fibronectin stimulation after TGF-beta treatment in cardiomyocytes. Trypanosoma cruzi infection elicited a decrease of 79.8% in the frequency of cardiomyocytes presenting TbetaRII striations, but did not interfere significantly in its expression. In addition, T. cruzi-infected cardiomyocytes present a lower response to exogenous TGF-beta, showing no enhancement of TbetaRII striations and a reduction of phosphorylated Smad 2, with no significant difference in TbetaRII expression when compared to uninfected cells. Together, these results suggest that the co-localization of TbetaRII with costameres is important in activating the TGF-beta signalling cascade, and that T. cruzi-derived cytoskeleton disorganization could result in altered or low TGF-beta response in infected cardiomyocytes. PMID- 26996786 TI - Instant Blood-Mediated Inflammatory Reaction in Hepatocyte Transplantation: Current Status and Future Perspectives. AB - Hepatocyte transplantation (HT) is emerging as a promising alternative to orthotopic liver transplantation (OLT) in patients with certain liver-based metabolic disease and acute liver failure. Hepatocytes are generally infused into the portal venous system, from which they migrate into the liver cell plates of the native organ. One of the major hurdles to the sustained success of this therapy is early cell loss, with up to 70% of hepatocytes lost immediately following infusion. This is largely thought to be due to the instant blood mediated inflammatory reaction (IBMIR), resulting in the activation of complement and coagulation pathways. Transplanted hepatocytes produce and release tissue factor (TF), which activates the coagulation pathway, leading to the formation of thrombin and fibrin clots. Thrombin can further activate a number of complement proteins, leading to the activation of the membrane attack complex (MAC) and subsequent hepatocyte cell death. Inflammatory cells including granulocytes, monocytes, Kupffer cells, and natural killer (NK) cells have been shown to cluster around transplanted hepatocytes, leading to their rapid clearance shortly after transplantation. Current research aims to improve cell engraftment and prevent early cell loss. This has been proven successful in vitro using pharmacological interventions such as melagatran, low-molecular-weight dextran sulphate, and N-acetylcysteine (NAC). Effective inhibition of IBMIR would significantly improve hepatocyte engraftment, proliferation, and function, providing successful treatment for patients with liver-based metabolic diseases. PMID- 26996784 TI - Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates. AB - INTRODUCTION: This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS: A total of 64 male Sprague Dawley(r) rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS: Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION: Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications. PMID- 26996785 TI - Distribution pattern of bovine viral diarrhoea virus type 1 genome in lymphoid tissues of experimentally infected sheep. AB - In this study, cellular localization and the distribution pattern of BVDV genome in lymphoid tissues during the course of experimental acute BVDV-1 infection of sheep was investigated. Tonsils, mesenteric lymph nodes (MLN) and spleen were collected on 3, 6, 9, 12 and 15 days post infection (dpi) from twenty 4-month-old lambs, experimentally inoculated intra-nasally with 5 * 10(5) TCID50 of a non cytopathic (ncp) BVDV-1 isolate, Ind-17555. Tissues collected from ten mock infected lambs served as controls. In situ hybridization (ISH) was carried out in paraformaldehyde fixed paraffin embedded tissue sections using digoxigenin labelled riboprobe targeting 5'-UTR of BVDV-1. BVDV genome was detected at all the intervals from 3 dpi to 15 dpi in the lymphoid tissues with variations between the intervals and also amongst the infected sheep. During the early phase of acute infection, presence of viral genome was more in tonsils than MLN and spleen, whereas the distribution was higher in MLN during later stages. BVDV-1 genome positive cells included lymphocytes, macrophages, plasma cells, reticular cells and sometimes crypt epithelial cells. Genome distribution was frequently observed in the lymphoid follicles of tonsils, MLN and spleen, besides the crypt epithelium in tonsils, paracortex and medullary sinus and cords of MLN. Most abundant and widespread distribution of BVDV-1 genome was observed on 6 dpi while there was a reduction in number and intensity of positive signals by 15 dpi in most of the infected animals. This is the first attempt made to study the localisation of BVDV-1 in lymphoid tissues of acutely infected sheep by in situ hybridization. The results show that the kinetics of BVDV-1 distribution in lymphoid tissues of experimentally infected non-pregnant sheep follows almost a similar pattern to that demonstrated in BVDV infected cattle. PMID- 26996787 TI - Increased Serum Level of Growth Differentiation Factor 15 (GDF-15) is Associated with Coronary Artery Disease. AB - AIM: There is evidence suggesting that inflammatory responses play a critical role in the development of coronary artery disease (CAD). Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine. It increases during inflammatory processes and is associated with cardiometabolic risk. However, the relation between GDF-15 and CAD remains largely unknown. Herein, we aimed to evaluate serum GDF-15 levels and predictive values in patients with CAD. METHODS: Serum levels of GDF-15 in 105 patients with CAD and 96 healthy controls were measured by the enzyme-linked immunosorbent assay. Gensini scores were used to assess severity of CAD. The correlations between the serum GDF-15 levels and Gensini scores were examined using Spearman's correlation. Receivers operating characteristic (ROC) curve analysis was performed to determine the predictive values of GDF-15 levels. RESULTS: We found that serum GDF-15 levels were significantly increased in CAD group compared with healthy controls group (P < 0.001). Additionally, a positive correlation was observed between GDF-15 and the Gensini score (r = 0.85, P < 0.001). Moreover, the area under the ROC curve assay yielded a satisfactory result of 0.96 (95% confidence interval 0.94-0.98; P < 0.001), and the serum GDF-15 level had a 80.0% sensitivity and 91.7% specificity for predicting CAD. CONCLUSIONS: These data suggested that increased GDF-15 levels were positively associated with CAD, and GDF-15 might be a useful adjunct in discriminating CAD. PMID- 26996788 TI - Short interspersed nuclear elements (SINEs) are abundant in Solanaceae and have a family-specific impact on gene structure and genome organization. AB - Short interspersed nuclear elements (SINEs) are highly abundant non-autonomous retrotransposons that are widespread in plants. They are short in size, non coding, show high sequence diversity, and are therefore mostly not or not correctly annotated in plant genome sequences. Hence, comparative studies on genomic SINE populations are rare. To explore the structural organization and impact of SINEs, we comparatively investigated the genome sequences of the Solanaceae species potato (Solanum tuberosum), tomato (Solanum lycopersicum), wild tomato (Solanum pennellii), and two pepper cultivars (Capsicum annuum). Based on 8.5 Gbp sequence data, we annotated 82 983 SINE copies belonging to 10 families and subfamilies on a base pair level. Solanaceae SINEs are dispersed over all chromosomes with enrichments in distal regions. Depending on the genome assemblies and gene predictions, 30% of all SINE copies are associated with genes, particularly frequent in introns and untranslated regions (UTRs). The close association with genes is family specific. More than 10% of all genes annotated in the Solanaceae species investigated contain at least one SINE insertion, and we found genes harbouring up to 16 SINE copies. We demonstrate the involvement of SINEs in gene and genome evolution including the donation of splice sites, start and stop codons and exons to genes, enlargement of introns and UTRs, generation of tandem-like duplications and transduction of adjacent sequence regions. PMID- 26996789 TI - [Postoperative radiotherapy for non-small cell lung cancer: Efficacy, target volume, dose]. AB - The rate of local failure of stage IIIA-N2 non-small cell lung cancer is 20 to 40%, even if they are managed with surgery and adjuvant chemotherapy. Postoperative radiotherapy improves local control, but its benefit on global survival remains to be demonstrated. Considered for many years as an adjuvant treatment option for pN2 cancers, it continues nevertheless to be deemed too toxic. What is the current status of postoperative radiotherapy? The Lung Adjuvant Radiotherapy Trial (Lung ART) phase III trial should give us a definitive, objective response on global survival, but inclusion of patients is difficult. The results are consequently delayed. The aim of this review is to show all the results about efficacy and tolerance of postoperative radiotherapy and to define the target volume and dose to prescribe. PMID- 26996790 TI - [Pediatric medulloblastoma: Retrospective series of 52 patients]. AB - PURPOSE: Retrospective analysis of the results of 52 children irradiated for a medulloblastoma. PATIENTS AND METHODS: Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy. RESULTS: After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis. CONCLUSION: These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols. PMID- 26996792 TI - Preparing the health workforce in Ethiopia: A Cross-sectional study of competence of anesthesia graduating students. AB - BACKGROUND: Efforts to address shortages of health workers in low-resource settings have focused on rapidly increasing the number of higher education programs for health workers. This study examines selected competencies achieved by graduating Bachelor of Science and nurse anesthetist students in Ethiopia, a country facing a critical shortage of anesthesia professionals. METHODS: The study, conducted in June and July 2013, assessed skills and knowledge of 122 students graduating from anesthetist training programs at six public universities and colleges in Ethiopia; these students comprise 80% of graduates from these institutions in the 2013 academic year. Data was collected from direct observations of student performance, using an objective structured clinical examination approach, and from structured interviews regarding the adequacy of the learning environment. RESULTS: Student performance varied, with mean percentage scores highest for spinal anesthesia (80%), neonatal resuscitation (74%), endotracheal intubation (73%), and laryngeal mask airway insertion check (71%). Average scores were lowest for routine anesthesia machine check (37%) and preoperative screening assessment (48%). Male graduates outscored female graduates (63.2% versus 56.9%, P = 0.014), and university graduates outscored regional health science college graduates (64.5% versus 55.5%, P = 0.023). Multivariate linear regression found that competence was associated with being male and attending a university training program. Less than 10% of the students believed that skills labs had adequate staff and resources, and only 57.4% had performed at least 200 endotracheal intubations at clinical practicum sites, as required by national standards. DISCUSSION: Ethiopia has successfully expanded higher education for anesthetists, but a focus on quality of training and assessment of learners is required to ensure that graduates have mastered basic skills and are able to offer safe services. PMID- 26996794 TI - Psychometric properties of the dundee ready educational environment measure in a sample of Ghanaian Medical Students. AB - BACKGROUND: The Dundee Ready Educational Environment Measure (DREEM) has been widely accepted and recognized for the assessment of the educational environment in a variety of health professions education programs. Concerns regarding the psychometric properties of the DREEM have been raised. This study evaluated the psychometric properties of the DREEM in a sample of Ghanaian medical students following a problem-based learning curriculum. METHODS: A sample of 234 second to fourth year medical students of the University for Development Studies, School of Medicine and Health Sciences were invited to complete the DREEM questionnaire. Psychometric measures employed included Cronbach's alpha analysis, confirmatory factor analysis and principal component analysis with varimax rotation. RESULTS: The internal consistency for the overall DREEM was 0.92. Apart from two subscales that had Cronbach's alpha values < 0.70, the remainder had values ranging from 0.73 - 0.78. Confirmatory factor analysis did not support the original five factor structure of the DREEM. Large significant correlation coefficients were found between the five factors raising concerns about the independency of the individual subscales. Exploratory factor analysis suggested various factor solutions ranging from 4 to 14 factors. The four factor structure was interpretable and was maintained. All of the four factors achieved eigenvalues > 1, and in total they accounted for 37.6% of the variance. Alpha values for the subscales of the new four factor structure ranged from 0.618 - 0.915. DISCUSSION: The overall internal consistency of the DREEM was found to be excellent. The internal consistency of the individual subscales was variable, as two subscales had alpha values < 0.70 and the remainder exceeding 0.70. The original five factor structure of the DREEM was not supported. Exploratory factor analysis suggested a four factor solution as a possible alternative to the five factor structure of the DREEM. PMID- 26996793 TI - Learning professional ethics: Student experiences in a health mentor program. AB - BACKGROUND: The use of patient centred approaches to healthcare education is evolving, yet the effectiveness of these approaches in relation to professional ethics education is not well understood. The aim of this study was to explore the experiences and learning of health profession students engaged in an ethics module as part of a Health Mentor Program at the University of Toronto. METHODS: Students were assigned to interprofessional groups representing seven professional programs and matched with a health mentor. The health mentors, individuals living with chronic health conditions, shared their experiences of the healthcare system through 90 minute semi-structured interviews with the students. Following the interviews, students completed self-reflective papers and engaged in facilitated asynchronous online discussions. Thematic analysis of reflections and discussions was used to uncover pertaining to student experiences and learning regarding professional ethics. RESULTS: Five major themes emerged from the data: (1) Patient autonomy and expertise in care; (2) ethical complexity and its inevitable reality in the clinical practice setting; (3) patient advocacy as an essential component of day-to-day practice; (4) qualities of remarkable clinicians that informed personal ideals for future practice; (5) patients' perspectives on clinician error and how they enabled suggestions for improving future practice. DISCUSSION: The findings of a study in one university context suggest that engagement with the health mentor narratives facilitated students' critical reflection related to their understanding of the principles of healthcare ethics. PMID- 26996795 TI - Intersecting gender, evaluations, and examinations: Averting gender bias in an obstetrics and gynecology clerkship in the United States. AB - BACKGROUND: The purpose of this study was to determine whether gender bias was present in the final third-year medical student obstetrics/gynecology clerkship performance evaluation completed by faculty and resident physicians. METHODS: This was a retrospective cohort study of third-year medical students over the course of ten years (2004 - 2014) at a private medical school in the northern US state of Wisconsin. Each student's performance during their required 6-week obstetrics/gynecology clerkship was assessed by a combination of the student's scores on a clinical performance evaluation and on a standardized national subject examination. The clinical performance evaluations are comprised of 10 domains, each using a 9-point Likert scale and completed by faculty and resident physicians. All clerkships at our institution use the same evaluation form, which was designed and validated by the medical education statistics department. Final obstetrics/gynecology clerkship average clinical evaluation scores (Scale 1-9) and obstetrics/gynecology standardized national subject examination scores (Percentile 1-99) were compared to see if a gender based difference between subject examination and performance evaluation scores existed. RESULTS: 1,976 student records were analyzed. Mean standardized national subject exam scores were significantly higher for females [74.4 (8.1)] than males [72.9 (8.2)] (Possible range 1-99) with Cohen's d = 0.2 (P = 0.001). The average female score on the clinical evaluation was mean (SD) = 7.4 (0.9), compared to an average clinical evaluation score of 7.2 (1.0) for males (P = 0.001) (range 1-9). Performance on the standardized national subject exam was significantly correlated (r = 0.3, P = 0.001) with clinical evaluation scores, and when split by gender the strength of the correlation remained. DISCUSSION: Medical student performance on the standardized national subject exam correlated with clinical evaluations independent of gender. Women had higher scores on both the subject examination and the clinical performance evaluations. There was no evidence of gender bias in the students' clinical evaluation scores. PMID- 26996796 TI - EpiAssist: Service-learning in public health education. AB - BACKGROUND: Although public health degree programs typically require practica and other field experiences, service-learning courses, with a focus on civic engagement and the application of classroom learning in real world settings, can go beyond these requirements and provide benefits to students and community-based practice partners. The goal of this paper is to assess potential benefits of service-learning programs for both graduate-level public health students and state and local public health agency partners. METHODS: EpiAssist is a new service-learning program developed at the School of Public Health of the Texas A and M University Health Science Center, USA, in January 2015. EpiAssist was integrated into a new course, Methods in Field Epidemiology. The integration of service-learning was guided by a partnership with the Texas A and M Center for Teaching Excellence. RESULTS: State, regional, and local public health partners requested EpiAssist via email or telephone. A listserv was used to recruit student volunteers to meet requests. 54 of 86 registered EpiAssist students (63%) participated in at least one of ten service-learning and three training activities between January and June, 2015. Service-learning activities included questionnaire development, in-person and telephone data collection, and data analysis. Training topics for students included the Epi InfoTM software, community assessment and communicable disease reporting. Students and partner organizations provided generally positive assessments of this service learning program through an online evaluation. DISCUSSION: Service-learning provides students with enhanced classroom learning through applied public health experience in state, regional and local health departments. These experiences provide both needed surge capacity to public health departments and valuable hands-on field experience to students. PMID- 26996798 TI - India's foreign medical graduates: an opportunity to correct India's physician shortage. AB - BACKGROUND: India's current estimated doctor-population ratio of 1:1700 against targeted ratio of 1: 1000 shows a clear shortage. A mismatch in number of medical aspirants and available seats, intense competition and unaffordable costs of medical education prompt many Indian students to pursue training opportunities abroad. Many later return to India, and these foreign medical graduates (FMGs) must pass a qualification test which is a required to practice medicine in India. This review undertakes a situational analysis of FMGs in India and suggests a roadmap to better utilize this resource pool of physicians. METHODS: A thorough literature search was carried out using Google Scholar, PubMed and websites of the Central Board of Secondary Education and Medical Council of India. Foreign Medical Graduate Examination (FMGE) data was obtained from India's National Board of Examinations. RESULTS: From 2002 to 2014, growth was seen in the number of FMGs who took the FMGE, with more having trained in China than any other country. However, typically only 25% of FMGs pass the FMGE. In 2013, 9,700 FMGs were unable to pass the FMGE to enter practice in India. At least 7,500 FMG physicians are unable to become licensed each year for failure to pass the FMGE, including those who retake and again fail the exam. DISCUSSION: There are possible solutions. Additional training and hands-on apprenticeships can be introduced to help FMGs build their skills to then be able to pass the FMGE. FMGs can now learn by participating as observers in the established programs. Opportunities also exist for FMGs to work outside of clinical care, including in research, hospital administration and public health. As of now, FMGs are an untapped resource and lost opportunity to a country with shortages of physicians. PMID- 26996797 TI - Evaluation of a training DVD on pneumococcal conjugate vaccine for Kenyan EPI healthcare workers. AB - BACKGROUND: The Kenyan Ministry of Public Health and Sanitation was the first in Africa to introduce the new 10-valent Pneumococcal Conjugate Vaccine, PCV-10, in 2011. For successful implementation and to avoid adverse events following immunisation, specific training on handling and storage of the PCV-10 vaccine was required. Therefore, a training DVD was recorded in English and partly in Kiswahili to be used in combination with in-classroom training. Since the Kenyan Immunisation Programme was the first to use a DVD for training healthcare workers, an evaluation was done to obtain feedback on content, format and use, and propose suggestions to improve quality and uptake of the DVD. METHODS: Feedback was obtained from nurses and vaccinology course participants through the completion of a questionnaire. Nurses also participated in focus group discussions and trainers in key informant interviews. RESULTS: Twelve trainers, 72 nurses and 26 international vaccinology course participants provided feedback, with some notable differences between the three study groups. The survey results confirmed the acceptability of the content and format, and the feasibility of using the DVD in combination with in-classroom teaching. To improve the quality and adoption of the DVD, key suggestions were: Inclusion of all EPI vaccines and other important health issues; broad geographic distribution of the DVD; and bilingual English/Kiswahili use of languages or subtitles. DISCUSSION: The Kenyan DVD is appreciated by a heterogeneous and international audience rendering the DVD suitable for other Anglophone African countries. Differences between feedback from nurses and vaccinology course participants can be explained by the practical approach of the DVD and the higher education and service level of the latter. A drawback is the use of DVD players and televisions due to lack of electricity, but it is a matter of time before all rural health facilities in Africa will have access to electricity and modern technology. PMID- 26996799 TI - Medical education resources initiative for teens program in baltimore: A model pipeline program built on four pillars. AB - BACKGROUND: Less than 6% of U.S. medical school applicants are African-American. The lack of diversity among physicians, by race as well as other measures, confers a negative impact on the American healthcare system because underrepresented minority (URM) physicians are more likely to practice in underserved communities and deliver more equitable, culturally competent care. METHODS: MERIT (Medical Education Resources Initiative for Teens) is a nonprofit organization based in Baltimore, Maryland, USA. MERIT prepares URM high school students for health careers by providing a holistic support system for seven consecutive years. The program model, which utilizes weekly Saturday sessions, summer internships, and longitudinal mentoring, is built on four foundational pillars: (1) Ignite the Fire, (2) Illuminate the Path, (3) Create the Toolkit, and (4) Sustain the Desire. RESULTS: Since 2011, MERIT has supported 51 students in the Baltimore City Public School System. For the past two years, 100% (n = 14) of MERIT seniors enrolled in universities, compared to only 20.2% of Baltimore City students overall. While it is too early to know whether MERIT alumni will realize their goals of becoming healthcare professionals, they are currently excelling in universities and over 75% (n = 17) are still planning to pursue graduate degrees in health-related fields. DISCUSSION: After piloting an effective program model, MERIT now has three key priorities moving forward: (1) Creating a sustainable and thriving organization, (2) increasing the number of scholars the program supports in Baltimore, and (3) expanding MERIT to other cities. PMID- 26996800 TI - Addressing outpatient continuity for ambulatory training: A novel tool for longitudinal primary care sign out. AB - BACKGROUND: We created a tool to improve communication among health professional trainees in the ambulatory setting. The tool was devised to both inform practice partner teams about high-risk patients and assign patient follow-up issues to team members. Team members were internal medicine residents and nurse practitioner fellows in the VA Connecticut Healthcare System Center of Excellence in Primary Care Education (CoEPCE), an interprofessional training model in primary care. METHODS: We used a combination of Likert scale response questions and open ended questions to evaluate trainee attitudes before and after the implementation of the tool, as well as solicited feedback to improve the tool. RESULTS: After using the primary care sign out tool, trainees expressed greater confidence that they could identify high-risk patients that had been cared for by other trainees and that important patient care issues would be followed up by others when they were not in clinic. In terms of areas for improvement, respondents wanted to have the sign out tool posted online. DISCUSSION: Our sign out tool offers a strategy that others can use to improve communication and knowledge of shared patients within teams comprised of interprofessional trainees. PMID- 26996801 TI - Getting undergraduate medical students involved in research. PMID- 26996802 TI - Candy lectures: Can Incentive improve the quality of student preparation in clinical lectures? PMID- 26996803 TI - Learning styles and learning approaches - Are they different? PMID- 26996804 TI - Use of the geographic information system in health assessment: An Experience in Medical Undergraduate Teaching in India. PMID- 26996805 TI - Patients' perceptions of participation in educational home visits. PMID- 26996806 TI - Integrated profiling methods for identifying the targets of bioactive compounds: MorphoBase and ChemProteoBase. AB - Covering: up to the end of 2015.Many useful compounds from natural products have been discovered through phenotype-based screening. However, the target identification process for compounds is laborious and time-consuming. With the development of new equipment and methodologies for biological analyses, a variety of profiling methods that utilize large sets of experimental data have been established. Here, we highlight the utility of our identification approaches, MorphoBase and ChemProteoBase. PMID- 26996807 TI - Spatial structure of states of self stress in jammed systems. AB - States of self stress, organizations of internal forces in many-body systems that are in equilibrium with an absence of external forces, can be thought of as the constitutive building blocks of the elastic response of a material. In overconstrained disordered packings they have a natural mathematical correspondence with the zero-energy vibrational modes in underconstrained systems. While substantial attention in the literature has been paid to diverging length scales associated with zero- and finite-energy vibrational modes in jammed systems, less is known about the spatial structure of the states of self stress. In this work we define a natural way in which a unique state of self stress can be associated with each bond in a disordered spring network derived from a jammed packing, and then investigate the spatial structure of these bond-localized states of self stress. This allows for an understanding of how the elastic properties of a system would change upon changing the strength or even existence of any bond in the system. PMID- 26996808 TI - New KEL*01M and KEL*02M alleles: structural modeling to assess the impact of amino acid changes. AB - BACKGROUND: The KELL antigens are carried by the well-folded and highly polymorphic glycoprotein KELL, belonging to the M13 family of metalloproteases. Anti-KEL, particularly anti-KEL1, are clinically significant. We retrospectively investigated genomic DNA from samples with uncertain KEL1 or KEL2 phenotype and identified six novel Kmod alleles. We then considered a model of the protein three-dimensional (3D) structure to assess the impacts of the amino acid changes. STUDY DESIGN AND METHODS: The 19 exons of the KEL gene were polymerase chain reaction amplified and sequenced. Modeling was performed using the experimental 3D structure of human endothelin-converting enzyme-1 in the presence of the metabolite phosphoramidon. RESULTS: We identified four novel KEL*01M alleles with amino acid substitutions p.Arg447Trp, p.Gly641Arg, p.Ala645Val, and p.Gly703Arg found buried within helices of the ectodomain catalytic lobe. We also revealed one new KEL*02M allele with p.Gly263Glu in contact with solvent (water) located within the second lobe of the ectodomain. One sample with c.575G>C transversion (p.Arg192Pro) on a KEL*02 background showed a weakened reactivity for KEL1. According to our 3D modeling, these amino acid substitutions may have a profound impact on the protein structure. CONCLUSION: This study is especially interesting with regard to the description of four new KEL*01M alleles. Indeed, to date only two KEL*01M alleles have been described and our data suggest a nonnegligible incidence of KEL1 variants. Serologic KEL2-negative results as well as any ambiguity implying either KEL1 or KEL2 in donors should always be confirmed by means of genotyping analysis and discrepancies between these methods require sequencing of KEL gene. PMID- 26996809 TI - Crosstalk between microbiota, pathogens and the innate immune responses. AB - Research in the last decade has convincingly demonstrated that the microbiota is crucial in order to prime and orchestrate innate and adaptive immune responses of their host and influence barrier function as well as multiple developmental and metabolic parameters of the host. Reciprocally, host reactions and immune responses instruct the composition of the microbiota. This review summarizes recent evidence from experimental and human studies which supports these arms of mutual relationship and crosstalk between host and resident microbiota, with a focus on innate immune responses in the gut, the role of cell death pathways and antimicrobial peptides. We also provide some recent examples on how dysbiosis and pathogens can act in concert to promote intestinal infection, inflammatory pathologies and cancer. The future perspectives of these combined research efforts include the discovery of protective species within the microbiota and specific traits and factors of microbes that weaken or enforce host intestinal homeostasis. PMID- 26996810 TI - Global analysis of the impact of linezolid onto virulence factor production in S. aureus USA300. AB - The translation inhibitor linezolid is an antibiotic of last resort against Gram positive pathogens including methicillin resistant strains of the nosocomial pathogen Staphylococcus aureus. Linezolid is reported to inhibit production of extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to linezolid in general and the inhibition of virulence factor synthesis in particular a holistic study was performed. Linezolid was added to exponentially growing S. aureus cells and the linezolid stress response was analyzed with transcriptomics and quantitative proteomics methods. In addition, scanning and transmission electron microscopy experiments as well as fluorescence microscopy analyses of the cellular DNA and membrane were performed. As previously observed in studies on other translation inhibitors, S. aureus adapts its protein biosynthesis machinery to the reduced translation efficiency. For example the synthesis of ribosomal proteins was induced. Also unexpected results like a decline in the amount of extracellular and membrane proteins were obtained. In addition, cell shape and size changed after linezolid stress and cell division was diminished. Finally, the chromosome was condensed after linezolid stress and lost contact to the membrane. These morphological changes cannot be explained by established theories. A new hypothesis is discussed, which suggests that the reduced amount of membrane and extracellular proteins and observed defects in cell division are due to the disintegration of transertion complexes by linezolid. PMID- 26996811 TI - Four-week exercise program does not change rotator cuff muscle activation and scapular kinematics in healthy subjects. AB - Rotator cuff and scapular muscle strengthening exercises are an essential part of shoulder rehabilitation and sports training. Although the effect of exercise training on pain and function have been widely investigated, few studies have focused on the changes in shoulder kinematics and muscle activity after exercise training. Therefore, the purpose of the present study was to investigate the effect of rotator cuff and scapular strengthening exercises on shoulder kinematics and the activation of rotator cuff and scapular muscles in healthy subjects. Thirty-six healthy subjects were recruited and randomly assigned into either a training or control group. Subjects in the training group were trained with rotator cuff and scapular strengthening exercises for 4 weeks. Scapular kinematics and shoulder muscle activity during arm elevation were measured before and after exercise training. After the 4-week training protocol, there was an increase in strength and a decrease in upper trapezius activation in the training group, which is consistent with previous studies. However, no difference was found in scapular kinematics and activation of rotator cuff muscles between the control and training groups after the training protocol. Although the exercise protocol resulted in strength gains for the rotator cuff, these gains did not transfer to an increase in muscle activation during motion. These results demonstrate the difficulty in changing activation patterns of the rotator cuff muscles. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2079-2088, 2016. PMID- 26996813 TI - Fermentation of rapeseed meal, sunflower meal and faba beans in combination with wheat bran increases solubility of protein and phosphorus. AB - BACKGROUND: To increase self-supply of protein and phosphorus (P) in European pig and poultry diets and reduce nitrogen (N) and P excretion, attention is directed to approaches increasing protein and P digestibility of rapeseed, sunflower and faba beans. Wheat bran is rich in enzymes degrading and solubilizing protein and phytate. Herein, solubilization of protein, N and P was investigated when increasing ratios of wheat bran were fermented with rapeseed meal (RSM), sunflower meal (SFM), faba beans (FB) or a combination of these (RSM/SFM/FB). RESULTS: Protein, N and P solubility was greater, for all mixtures, the more wheat bran was included and the longer the mixtures were fermented. The increase in N (FB > RSM/SFM/FB > SFM > RSM) and protein solubility (RSM/SFM/FB > RSM > SFM > FB) was greatest from day 0 to day 3 and thereafter limited, whereas P solubility increased during the whole period (5 days; FB > RSM/SFM/FB > SFM > RSM). In general, FB showed the highest solubility and highest increase in N and P solubility, while RSM showed the highest protein solubility and RSM/SFM/FB the highest increase in protein solubility. CONCLUSION: Fermentation of RSM, SFM, FB and RSM/SFM/FB without or with wheat bran uncovers a potential for increased protein and P digestibility and thereby reduced N and P excretion from pigs and poultry. (c) 2016 Society of Chemical Industry. PMID- 26996814 TI - Diagnostic value of haemoglobin A1c in post-partum screening of women with gestational diabetes mellitus. AB - AIMS: The aim of this study was to evaluate whether women with gestational diabetes mellitus could be screened using HbA1c for glucose metabolism status at 6-12 weeks post-partum. METHODS: We enrolled 699 pregnant women diagnosed with gestational diabetes mellitus from October 2005 to December 2013. A 75-g oral glucose tolerance test (OGTT) and HbA1c measurement were performed at 6-12 weeks after delivery. RESULTS: The prevalence of overt diabetes and pre-diabetes were 5.2% (n = 36) and 49.1% (n = 343), respectively, when using the 75-g OGTT as the gold standard. HbA1c alone identified 2.9% (n = 20) as having overt diabetes and 32.2% (n = 225) as having pre-diabetes. When American Diabetes Association cut offs were applied, the sensitivity and specificity for HbA1c to diagnose overt diabetes were 19.4% and 98.0%, respectively. Pre-diabetes, according to the HbA1c criterion, had 41.2% sensitivity and 72.2% specificity. The misclassifications identified 97 positive differences, 233 negative differences and 369 ties (P < 0.05). The area under the receiver operating characteristic curves for detecting diabetes and pre-diabetes were 0.615 [95% confidence interval (95% CI), 0.515 to 0.716] and 0.588 (95% CI, 0.545 to 0.630), respectively. CONCLUSIONS: HbA1c may not be sensitive enough for an accurate diagnosis, but it is highly specific for diagnosing overt diabetes at 6-12 weeks post-partum in women with previous gestational diabetes mellitus. PMID- 26996812 TI - Human Papillomavirus and Head and Neck Cancer: Psychosocial Impact in Patients and Knowledge of the Link - A Systematic Review. AB - Head and neck cancer (HNC) currently affects approximately 11 200 people in the UK, with an increasing proportion known to be caused by the human papillomavirus (HPV). We undertook a systematic review of studies measuring the psychosocial impact of HPV-related HNC and also studies measuring knowledge about the link between HPV and HNC among different populations. Searches were conducted on MEDLINE, Embase, PsycINFO, CINAHL Plus and Web of Science, with reference and forward citation searches also carried out on included studies. Studies were selected if they (i) were original peer-reviewed research (qualitative or quantitative), (ii) mentioned HPV and HNC, (iii) measured an aspect of the psychosocial impact of the diagnosis of HPV-related HNC as the dependent variable and/or (iv) measured knowledge of the association between HPV and HNC. In total, 51 papers met the inclusion criteria; 10 measuring psychosocial aspects and 41 measuring knowledge of the link between HPV and HNC. Quality of life in those with HPV-positive HNC was found to be higher, lower or equivalent to those with HPV-negative HNC. Longitudinal studies found quality of life in patients was at its lowest 2-3 months after diagnosis and some studies found quality of life almost returned to baseline levels after 12 months. Knowledge of the link between HPV and HNC was measured among different populations, with the lowest knowledge in the general population and highest in medical and dental professionals. Due to the limited studies carried out with patients measuring the psychosocial impact of a diagnosis of HPV-positive HNC, future work is needed with the partners of HPV-positive HNC patients and health professionals caring for these patients. The limited knowledge of the association between HPV and HNC among the general population also indicates the need for research to explore the information that these populations are receiving. PMID- 26996815 TI - Fabrication, characterization, and biological assessment of multilayer laminin gamma2 DNA coatings on titanium surfaces. AB - The purpose of this work was to fabricate a multilayer laminin gamma2 DNA coating on a titanium surface and evaluate its biological properties. A multilayer laminin gamma2 DNA coating was fabricated on titanium using a layer-by-layer assembly technique. The rate of coating degradation was evaluated by detecting the amount of cDNA remaining. Surface analysis using X-ray photoelectron spectroscopy, atomic force microscopy, and surface contact angle measurements revealed the multilayer structure to consist of cationic lipid and confirmed that a laminin gamma2 DNA layer could be fabricated on titanium via the layer-by-layer assembly process. The transfection efficiency was highest for five layers in the multilayer structure. HEK293 cells cultured on the multilayer films displayed significantly higher adhesion activity than the control group. The expression of laminin gamma2 and the co-localization of integrin beta4 and plectin were more obvious in HN4 cells cultured on the multilayer laminin gamma2 DNA coating, while weak immunoreactivities were observed in the control group. We concluded that the DNA-loaded multilayer provided a surface with good biocompatibility and that the multilayer laminin gamma2 DNA coating might be effective in improving cell adhesion and the formation of hemidesmosomes on titanium surfaces. PMID- 26996817 TI - Social behavior, hormones and adult neurogenesis. AB - A variety of experiences have been shown to affect the production of neurons in the adult hippocampus. These effects may be mediated by experience-driven hormonal changes, which, in turn, interact with factors such as sex, age and life history to alter brain plasticity. Although the effects of physical experience and stress have been extensively characterized, various types of social experience across the lifespan trigger profound neuroendocrine changes in parallel with changes in adult neurogenesis. This review article focuses on the influence of specific social experiences on adult neurogenesis in the dentate gyrus and the potential role of hormones in these effects. PMID- 26996816 TI - Au-NiCo2O4 supported on three-dimensional hierarchical porous graphene-like material for highly effective oxygen evolution reaction. AB - A three-dimensional hierarchical porous graphene-like (3D HPG) material was synthesized by a one-step ion-exchange/activation combination method using a cheap metal ion exchanged resin as carbon precursor. The 3D HPG material as support for Au-NiCo2O4 gives good activity and stability for oxygen evolution reaction (OER). The 3D HPG material is induced into NiCo2O4 as conductive support to increase the specific area and improve the poor conductivity of NiCo2O4. The activity of and stability of NiCo2O4 significantly are enhanced by a small amount of Au for OER. Au is a highly electronegative metal and acts as an electron adsorbate, which is believed to facilitate to generate and stabilize Co(4+) and Ni(3+) cations as the active centres for the OER. PMID- 26996818 TI - Endocrine and social regulation of adult neurogenesis in songbirds. AB - The identification of pronounced seasonal changes in the volume of avian song control nuclei stimulated the discovery of adult neurogenesis in songbirds as well as renewed studies in mammals including humans. Neurogenesis in songbirds is modulated by testosterone and other factors such as photoperiod, singing activity and social environment. Adult neurogenesis has been widely studied by labeling, with tritiated thymidine or its analog BrdU, cells duplicating their DNA in anticipation of their last mitotic division and following their fate as new neurons. New methods based on endogenous markers of cell cycling or of various stages of neuronal life have allowed for additional progress. In particular immunocytochemical visualization of the microtubule-associated protein doublecortin has provided an integrated view of neuronal replacement in the song control nucleus HVC. Multiple questions remain however concerning the specific steps in the neuronal life cycle that are modulated by various factors and the underlying cellular mechanisms. PMID- 26996819 TI - Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documents. AB - OBJECTIVE: To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. DESIGN: A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. SETTING: For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. PARTICIPANTS: Individuals contributing ADR information to product information documents. MAIN OUTCOMES MEASURES: All ADRs reported in product information sections 5 and 6 (USA), and 4.4 and 4.8 (Europe). RESULTS: Twelve brand drugs--24 paired documents--were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65-425) and 114 (range: 56-265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. CONCLUSIONS: Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to comprehensible and reliable ADR information. PMID- 26996820 TI - Perlecan expression influences the keratin 15-positive cell population fate in the epidermis of aging skin. AB - The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal-epidermal junction, a cell surface-associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well-differentiated multi-layered epithelium. Perlecan down-regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self-renewal capacity of basal keratinocytes. PMID- 26996822 TI - Development and validation of a photographic food atlas for portion size assessment in the southern plains of Nepal. AB - OBJECTIVE: To develop and validate a photographic food atlas of common foods for dietary assessment in southern Nepal. DESIGN: We created a life-sized photographic atlas of forty locally prepared foods. Between March and June 2014, data collectors weighed portion sizes that respondents consumed during one mealtime and then a different data collector revisited the household the next day to record respondents' estimations of their previous day's intakes using the atlas. Validity was assessed by percentage error, Cohen's weighted kappa (kappa w) and Bland-Altman limits of agreement. SETTING: Dhanusha and Mahottari districts in southern Nepal. SUBJECTS: A random sample of ninety-five adults in forty-eight rural households with a pregnant woman. RESULTS: Overall, respondents underestimated their intakes (mean error =-4.5 %). Rice and dal (spiced lentil soup) intakes were underestimated (-14.1 % and -34.5 %, respectively), but vegetable curry intake was overestimated (+20.8 %). Rice and vegetable curry portion size images were significantly reliably selected (Cohen's kappa w (se): rice=0.391 (0.105); vegetable curry=0.430 (0.139)), whereas dal images were not. Energy intake over one mealtime was under-reported by an average of 569 kJ (136 kcal; 4.5 % error) using recall compared with the weighing method. CONCLUSIONS: The photographic atlas is a useful tool for field estimation of dietary intake. Average errors were low, and there was 'modest' agreement between weighed and recalled portion size image selection of rice and vegetable curry food items. Error in energy estimation was low but with wide limits of agreement, suggesting that there is scope for future work to reduce error further. PMID- 26996823 TI - KO(t)Bu-Initiated Aryl C-H Iodination: A Powerful Tool for the Synthesis of High Electron Affinity Compounds. AB - An efficient iodination reaction of electron-deficient heterocycles is described. The reaction utilizes KO(t)Bu as an initiator and likely proceeds by a radical anion propagation mechanism. This new methodology is particularly effective for functionalization of building blocks for electron transport materials. Its utility is demonstrated with the synthesis of a new perylenediimide-thiazole non fullerene acceptor capable of delivering a power conversion efficiency of 4.5% in a bulk-heterojunction organic solar cell. PMID- 26996821 TI - Geospatial and age-related patterns of Taenia solium taeniasis in the rural health zone of Kimpese, Democratic Republic of Congo. AB - BACKGROUND: Taenia solium infections are mostly endemic in less developed countries where poor hygiene conditions and free-range pig management favor their transmission. Knowledge on patterns of infections in both human and pig is crucial to design effective control strategies. The aim of this study was to assess the prevalence, risk factors and spatial distribution of taeniasis in a rural area of the Democratic Republic of Congo (DRC), in the prospect of upcoming control activities. METHODS: A cross-sectional study was conducted in 24 villages of the health zone of Kimpese, Bas Congo Province. Individual and household characteristics, including geographical coordinates were recorded. Stool samples were collected from willing participants and analyzed using the copro-antigen enzyme-linked immunosorbent assay (copro-Ag ELISA) for the detection of taeniasis. Blood samples were collected from pigs and analyzed using the B158/B60 monoclonal antibody-based antigen ELISA (sero-Ag ELISA) to detect porcine cysticercosis. Logistic regression and multilevel analysis were applied to identify risk factors. Global clustering and spatial correlation of taeniasis and porcine cysticercosis were assessed using K functions. Local clusters of both infections were identified using the Kulldorff's scan statistic. RESULTS: A total of 4751 participants above 5 years of age (median: 23 years; IQR: 11-41) were included. The overall proportion of taeniasis positivity was 23.4% (95% CI: 22.2 24.6), ranging from 1 to 60% between villages, with a significant between household variance of 2.43 (SE=0.29, p<0.05). Taeniasis was significantly associated with age (p<0.05) and the highest positivity was found in the 5-10 years age group (27.0% (95% CI: 24.4-29.7)). Overall, 45.6% (95% CI: 40.2-51) of sampled pigs were sero-positive. The K functions revealed a significant overall clustering of human and pig infections but no spatial dependence between them. Two significant clusters of taeniasis (p<0.001; n=276 and n=9) and one cluster of porcine cysticercosis (p<0.001; n=24) were found. CONCLUSION: This study confirms high endemicity and geographical dispersal of taeniasis in the study area. The role of age in taeniasis patterns and significant spatial clusters of both taeniasis and porcine cysticercosis were evidenced, though no spatial correlation was found between human and pig infections. Urgent control activities are needed for this endemic area. PMID- 26996825 TI - Contrasting the effects of proton irradiation on dendritic complexity of subiculum neurons in wild type and MCAT mice. AB - Growing evidence suggests that radiation-induced oxidative stress directly affects a wide range of biological changes with an overall negative impact on CNS function. In the past we have demonstrated that transgenic mice over-expressing human catalase targeted to the mitochondria (MCAT) exhibit a range of neuroprotective phenotypes following irradiation that include improved neurogenesis, dendritic complexity, and cognition. To determine the extent of the neuroprotective phenotype afforded by MCAT expression in different hippocampal regions, we analyzed subiculum neurons for changes in neuronal structure and synaptic integrity after exposure to low dose (0.5 Gy) 150 MeV proton irradiation. One month following irradiation of WT and MCAT mice, a range of morphometric parameters were quantified along Golgi-Cox impregnated neurons. Compared with WT mice, subiculum neurons from MCAT mice exhibited increased trends (albeit not statistically significant) toward increased dendritic complexity in both control and irradiated cohorts. However, Sholl analysis of MCAT mice revealed significantly increased arborization of the distal dendritic tree, indicating a protective effect on secondary and tertiary branching. Interestingly, radiation-induced increases in postsynaptic density protein (PSD 95) puncta were not as pronounced in MCAT compared with WT mice, and were significantly lower after the 0.5 Gy dose. As past data has linked radiation exposure to reduced dendritic complexity, elevated PSD-95 and impaired cognition, reductions in mitochondrial oxidative stress have proven useful in ameliorating many of these radiation-induced sequelae. Data presented here shows similar trends, and again points to the potential benefits of reducing oxidative stress in the brain to attenuate radiation injury. Environ. Mol. Mutagen. 57:364-371, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26996824 TI - miR-34 activity is modulated through 5'-end phosphorylation in response to DNA damage. AB - MicroRNA (miRNA) expression is tightly regulated by several mechanisms, including transcription and cleavage of the miRNA precursor RNAs, to generate a mature miRNA, which is thought to be directly correlated with activity. MiR-34 is a tumour-suppressor miRNA important in cell survival, that is transcriptionally upregulated by p53 in response to DNA damage. Here, we show for the first time that there is a pool of mature miR-34 in cells that lacks a 5'-phosphate and is inactive. Following exposure to a DNA-damaging stimulus, the inactive pool of miR 34 is rapidly activated through 5'-end phosphorylation in an ATM- and Clp1 dependent manner, enabling loading into Ago2. Importantly, this mechanism of miR 34 activation occurs faster than, and independently of, de novo p53-mediated transcription and processing. Our study reveals a novel mechanism of rapid miRNA activation in response to environmental stimuli occurring at the mature miRNA level. PMID- 26996826 TI - Neighborhood Contextual Factors, Alcohol Use, and Alcohol Problems in the United States: Evidence From a Nationally Representative Study of Young Adults. AB - BACKGROUND: There is considerable variation in alcohol use and problems across the United States, suggesting that systematic regional differences might contribute to alcohol involvement. Several neighborhood contextual factors may be important aspects of this "alcohol environment." METHODS: Participants were 15,197 young adults (age 18 to 26) from Wave III of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative U.S. survey. Measures of past-year alcohol use and problems were obtained via structured in home interviews. Tract-level neighborhood contextual factors (density of on- and off-premises alcohol outlets, neighborhood disadvantage, rural vs. urban residence) were derived from census indicators and geocoded state-level alcohol outlet licenses. Multivariate logistic regression, ordered logistic regression, or negative binomial regression models, including age, sex, race, and household income as covariates, were fit to examine the relation of the neighborhood contextual factors with alcohol use and problems. RESULTS: The most consistent finding across 4 of the 5 measures of alcohol involvement was their association with neighborhood advantage; the active ingredient underlying this effect was primarily the proportion of educated residents in the neighborhood. The densities of alcohol outlets were associated with any alcohol use-they were not associated with binge drinking or alcohol problems, nor could they explain any of the neighborhood advantage effects. The influence of alcohol outlet densities on alcohol involvement did not differ for those above or below the legal age to purchase alcohol. Living in a rural versus an urban neighborhood was associated with a different alcohol use pattern characterized by a lower likelihood of any drinking, but among those who drank, consuming more alcohol per occasion. CONCLUSIONS: Living in a more advantaged and educated urban neighborhood with greater densities of bars and restaurants is associated with greater alcohol involvement among 18- to 26-year-olds in the United States. PMID- 26996828 TI - Deletion of a unique loop in the mycobacterial F-ATP synthase gamma subunit sheds light on its inhibitory role in ATP hydrolysis-driven H(+) pumping. AB - The F1 FO -ATP synthase is one of the enzymes that is essential to meet the energy requirement of both the proliferating aerobic and hypoxic dormant stages of the life cycle of mycobacteria. Most F-ATP synthases consume ATP in the alpha3 :beta3 headpiece to drive the gamma subunit, which couples ATP cleavage with proton pumping in the c ring of FO via the bottom of the gamma subunit. ATPase driven H(+) pumping is latent in mycobacteria. The presence of a unique 14 amino acid residue loop of the mycobacterial gamma subunit has been described and aligned in close vicinity to the c-ring loop Priya R et al. (2013) J Bioenerg Biomembr 45, 121-129 Here, we used inverted membrane vesicles (IMVs) of fast growing Mycobacterium smegmatis and a variety of covalent and non-covalent inhibitors to characterize the ATP hydrolysis activity of the F-ATP synthase inside IMVs. These vesicles formed a platform to investigate the function of the unique mycobaterial gamma loop by deleting the respective loop-encoding sequence (gamma166-179 ) in the genome of M. smegmatis. ATP hydrolysis-driven H(+) pumping was observed in IMVs containing the Deltagamma166-179 mutant protein but not for IMVs containing the wild-type F-ATP synthase. In addition, when compared to the wild-type enzyme, IMVs containing the Deltagamma166-179 mutant protein showed increased ATP cleavage and lower levels of ATP synthesis, demonstrating that the loop affects ATPase activity, ATPase-driven H(+) pumping and ATP synthesis. These results further indicate that the loop may affect coupling of ATP hydrolysis and synthesis in a different mode. PMID- 26996827 TI - Neocortical gamma oscillations in idiopathic generalized epilepsy. AB - OBJECTIVE: Absence seizures in patients with idiopathic generalized epilepsy (IGE) may in part be explained by a decrease in phasic GABAA (type-A gamma aminobutyric acid) receptor function, but the mechanisms are only partly understood. Here we studied the relation between ictal and interictal spike-wave discharges (SWDs) and electroencephalography (EEG) gamma oscillatory activity (30 60 Hz) in patients with IGE. METHODS: EEG recordings were obtained of 14 children with IGE (mean age, 8.5 +/- 5 years) and 14 age- and sex-matched controls. Time frequency analysis of each seizure and seizure-free control epochs was performed and cross-coherences of neocortical gamma oscillations were calculated to describe interictal and ictal characteristics of generalized seizures. RESULTS: SWDs were characterized with an abrupt increase of oscillatory activity of 3-4 and 13-60 Hz, peaking at 3-4 and 30-60 Hz, and with a simultaneous decrease in the 8-12 Hz frequency band. The rise in EEG gamma oscillations was short-lasting and decreased before activity declined at lower frequency ranges. Compared to control patients, patients with epilepsy also showed higher interictal values of mean coherence of gamma activity, but this interictal increase was not significant after post hoc analysis. SIGNIFICANCE: Our data support the hypothesis that gamma oscillatory activity increase concomitantly with rises in activity of lower EEG frequencies during absence seizures and that the activity starts to cease earlier than lower EEG frequencies. The data did not support a change in gamma activity preceding the 3-4 Hz SWDs. SWDs are hypothetically generated by the synchronous interaction between the thalamus and the cortex, whereas the production of gamma activity is the result of activity in local inhibitory networks. Thus, the modification of SWD by gamma activity may be understood in terms of the cellular and synaptic mechanisms involved. PMID- 26996829 TI - Impact of human T-cell leukemia virus type 1 on living donor liver transplantation: a multi-center study in Japan. AB - BACKGROUND: The natural history of human T-cell leukemia virus type 1 (HTLV-1), which causes adult T-cell leukemia (ATL) or HTLV-1 associated myelopathy, after liver transplantation is unclear. METHODS: We conducted a nationwide survey to investigate the impact of HTLV-1 status on living donor liver transplantation (LDLT) in Japan. We analyzed the cases of 82 HTLV-1-positive recipients and six HTLV-1-negative-before-LDLT recipients who received a hepatic graft from HTLV-1 positive donors. RESULTS: Adult T-cell leukemia developed in five recipients who ultimately died. Of these five, two received grafts from HTLV-1-positive donors and three from HTLV-1-negative donors. The 1-, 3-, and 5-year ATL development rates were 4.5%, 6.5%, and 9.2%, respectively. Fulminant hepatic failure as a pre transplant diagnosis was identified as an independent risk factor for ATL development (P = 0.001). The 1-, 3-, and 5-year survival rates for HTLV-1 positive recipients who received grafts from HTLV-1-negative donors were 79.9%, 66.1%, and 66.1%, and from HTLV-1-positive donors were 83.3%, 83.3%, and 60.8%, respectively. The 1-year survival rate for HTLV-1-negative recipients who received grafts from HTLV-1-positive donors was 33.3%. CONCLUSIONS: Fulminant hepatic failure is an independent risk factor for ATL development in HTLV-1 positive recipients. Grafts from HTLV-1-positive living donors can be transplanted into selected patients. PMID- 26996831 TI - Diagnostic Role of B-Type Natriuretic Peptide in Clinical Myocardial Injury Related to Neonatal Asphyxia. PMID- 26996830 TI - Oligosynaptic inhibition of group I afferents between the brachioradialis and flexor carpi radialis in humans. AB - Spinal reflex arcs mediated by low threshold afferents between the brachioradialis (BR) and flexor carpi radialis (FCR) were studied in eleven healthy human subjects using a post-stimulus time-histogram method. Electrical conditioning stimuli (ES) to the radial nerve branch innervating BR with the intensity below the motor threshold (MT) induced an early and significant trough (inhibition) in 32/85 FCR motor units (MUs) in 9/9 subjects. Such inhibition was never provoked by cutaneous stimulation. The central synaptic delay (CSD) of the inhibition was approximately 1.1ms longer than that of the homonymous FCR facilitation. ES to the median nerve branch innervating FCR with the intensity below MT induced an inhibition in 27/71 BR-MUs in 10/10 subjects. CSD of the inhibition was about 1.1ms longer than that of the homonymous BR facilitation. These findings suggest that inhibition between BR and FCR exists in humans. Group I afferents seem to mediate the inhibition through an oligo(di or tri)-synaptic path. PMID- 26996832 TI - Rhamnose synthase activity is required for pathogenicity of the vascular wilt fungus Verticillium dahliae. AB - The initial interaction of a pathogenic fungus with its host is complex and involves numerous metabolic pathways and regulatory proteins. Considerable attention has been devoted to proteins that play a crucial role in these interactions, with an emphasis on so-called effector molecules that are secreted by the invading microbe to establish the symbiosis. However, the contribution of other types of molecules, such as glycans, is less well appreciated. Here, we present a random genetic screen that enabled us to identify 58 novel candidate genes that are involved in the pathogenic potential of the fungal pathogen Verticillium dahliae, which causes vascular wilt diseases in over 200 dicotyledonous plant species, including economically important crops. One of the candidate genes that was identified concerns a putative biosynthetic gene involved in nucleotide sugar precursor formation, as it encodes a putative nucleotide-rhamnose synthase/epimerase-reductase (NRS/ER). This enzyme has homology to bacterial enzymes involved in the biosynthesis of the nucleotide sugar deoxy-thymidine diphosphate (dTDP)-rhamnose, a precursor of L-rhamnose, which has been shown to be required for virulence in several human pathogenic bacteria. Rhamnose is known to be a minor cell wall glycan in fungi and has therefore not been suspected as a crucial molecule in fungal-host interactions. Nevertheless, our study shows that deletion of the VdNRS/ER gene from the V. dahliae genome results in complete loss of pathogenicity on tomato and Nicotiana benthamiana plants, whereas vegetative growth and sporulation are not affected. We demonstrate that VdNRS/ER is a functional enzyme in the biosynthesis of uridine diphosphate (UDP)-rhamnose, and further analysis has revealed that VdNRS/ER deletion strains are impaired in the colonization of tomato roots. Collectively, our results demonstrate that rhamnose, although only a minor cell wall component, is essential for the pathogenicity of V. dahliae. PMID- 26996834 TI - Editorial: AMPK: New Frontiers in Human Diseases. PMID- 26996876 TI - Attitudes, knowledge and practices concerning delirium: a survey among intensive care unit professionals. AB - BACKGROUND: Delirium is a common form of vital organ dysfunction in intensive care unit (ICU) patients and is associated with poor outcomes. Adherence to guideline recommendations pertaining to delirium is still suboptimal. AIMS: We performed a survey aimed at identifying barriers for implementation that should be addressed in a tailored implementation intervention targeted at improved ICU delirium guideline adherence. DESIGN: The survey was conducted among ICU professionals. METHODS: An online survey was conducted among 360 ICU health care professionals (nurses, physicians and delirium consultants) from six ICUs in the southwest of the Netherlands as part of a multicentre prospective implementation project [response rate: 64% of 565 invited; 283 (79%) were nurses]. RESULTS: Although the majority (83%) of respondents considered delirium a common and major problem in the ICU, we identified several barriers for implementation of a delirium guideline. The most important barriers were knowledge deficit, low delirium screening rate, lack of trust in the reliability of delirium screening tools, belief that delirium is not preventable, low familiarity with delirium guidelines, low satisfaction with physician-described delirium management, poor collaboration between nurses and physicians, reluctance to change delirium care practices, lack of time, disbelief that patients would receive optimal care when adhering to the guideline and the perception that the delirium guideline is cumbersome or inconvenient in daily practice. CONCLUSION: Although ICU professionals consider delirium a serious problem, several important barriers to adhere to guidelines on delirium management are still present today. RELEVANCE TO CLINICAL PRACTICE: Identification of implementation barriers for adherence to guidelines pertaining to delirium is feasible with a survey. Results of this study may help to design-targeted implementation strategies for ICU delirium management. PMID- 26996877 TI - Sensorimotor dysfunction after limb fracture - An exploratory study. AB - BACKGROUND: Chronic pain is often associated with sensorimotor dysfunction but little is known about the early impact of limb fracture on sensory and motor performance. This exploratory study sought to assess these changes in patients with recent wrist and ankle fractures. A secondary aim was to determine the incidence of Complex Regional Pain Syndrome (CRPS) and its clinical features. METHODS: Fifty-three patients at a UK fracture centre underwent Quantitative Sensory Testing (QST), Motor Imagery (MI) and Body Perception Disturbance (BPD) assessments <=5 weeks post-fracture (Time 1). Subjective evaluation of recovery and clinical examination for CRPS was conducted 5 weeks later (Time 2, 50 patients). Patient-reported outcomes of pain, psychological distress and limb function were collected at Times 1 and 2, and 6 months after T1 (Time 3, 36 patients, postal questionnaire). RESULTS: Quantitative sensory testing at Time 1 demonstrated cold and pressure-pain hyperalgesia in the fractured limb compared to the non-fractured side (p < 0.05). Imagined movements were reported as significantly more difficult to perform on the fractured side (p < 0.001). There was evidence of BPD in the fractured limb, similar to that found in CRPS. The incidence of CRPS was 9.4%; however, individual signs and symptoms of the condition were commonly present (70% reported >= one symptom). Only 33% of patients reported to being 'back to normal' 6 months after fracture with 34% reporting ongoing pain. CONCLUSIONS: Limb fracture is associated with changes in pain perceptions, motor planning, and disruption to body perception. Signs and symptoms of CRPS, ongoing pain and delayed recovery post-fracture are common. WHAT DOES THIS STUDY ADD?: In the immediate post-fracture period: Body perception disturbance is reported in the fractured limb. Imagined movements of the fractured limb are less vivid and associated with pain This study contributes to the incidence literature on CRPS. PMID- 26996833 TI - The Balancing Act of Ribonucleotides in DNA. AB - The abundance of ribonucleotides in DNA remained undetected until recently because they are efficiently removed by the ribonucleotide excision repair (RER) pathway, a process similar to Okazaki fragment (OF) processing after incision by Ribonuclease H2 (RNase H2). All DNA polymerases incorporate ribonucleotides during DNA synthesis. How many, when, and why they are incorporated has been the focus of intense work during recent years by many labs. In this review, we discuss recent advances in ribonucleotide incorporation by eukaryotic DNA polymerases that suggest an evolutionarily conserved role for ribonucleotides in DNA. We also review the data that indicate that removal of ribonucleotides has an important role in maintaining genome stability. PMID- 26996878 TI - Periodic forces trigger knot untying during translocation of knotted proteins. AB - Proteins need to be unfolded when translocated through the pores in mitochondrial and other cellular membranes. Knotted proteins, however, might get stuck during this process, jamming the pore, since the diameter of the pore is smaller than the size of maximally tightened knot. The jamming probability dramatically increases as the magnitude of the driving force exceeds a critical value, Fc. In this numerical study, we show that for deep knots Fc lies below the force range over which molecular import motors operate, which suggest that in these cases the knots will tighten and block the pores. Next, we show how such topological traps might be prevented by using a pulling protocol of a repetitive, on-off character. Such a repetitive pulling is biologically relevant, since the mitochondrial import motor, like other molecular motors transforms chemical energy into directed motions via nucleotide-hydrolysis-mediated conformational changes, which are cyclic in character. PMID- 26996879 TI - Monotropein isolated from the roots of Morinda officinalis increases osteoblastic bone formation and prevents bone loss in ovariectomized mice. AB - Monotropein is a natural iridoid glycoside enriched in Morinda officinalis and has been used for medicinal purposes in China. In the present study, we systematically examined its effects on ovariectomy (OVX)-induced osteoporosis in mice and osteoblastic MC3T3-E1 cells for the first time. Eight-week-old female C57/BL6 mice were used to evaluate the osteoprotective effect of monotropein. Results showed that administration of monotropein (40 or 80 mg/kg/day) for four weeks exerted good bone protective effects as evidenced by the increase of bone mineral content (BMC), bone mineral density (BMD), bone volume fraction (BVF) and improvement of bone microstructure. Monotropein also enhanced the parameters of biomechanical properties, including maximum load, maximum stress and elastic modulus of femur in OVX mice. In addition, monotropein treatment decreased the serum levels of interleukin 1 (IL-1), interleukin 6 (IL-6) and soluble receptor activator of NF-kappaB ligand (sRANKL) in OVX mice. In this study, we also assessed the effects of monotropein on the proliferation and differentiation of osteoblastic MC3T3-E1 cells in vitro. After incubation for 48h, the cell proliferation was increased at the concentration of 10 MUM, 25 MUM, 50 MUM and 100 MUM. ALP activities were significantly increased after treatment with monotropein for 72h. Quantitative analyses with alizarin red staining showed significantly increased mineralization of MC3T3-E1 cells after treatment with monotropein for 28 days. Based on these results, monotropein may serve as a new candidate or a leading compound for antiosteoporosis. PMID- 26996880 TI - Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats. AB - Aminoglycosides are very effective antibiotics for the treatment of severe infections, but they rank among the most frequent causes of drug-induced nephrotoxicity. Thus, prevention of aminoglycoside nephrotoxicity is an unmet therapeutic objective. Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been reported to protect the kidney against toxic and ischemic acute kidney injury (AKI). We have assessed the effect of rat CT-1 in the severity of gentamicin (G)-induced AKI. Groups of male Wistar rats received the following for 6 consecutive days: i) isotonic saline solution (group CONT), ii) G, 150mg/kg/day, i.p. (group G), iii) CT-1, 100MUg/kg/day i.v. (group CT-1), or iv) G and CT-1 at the doses described above. The G group showed a manifest AKI characterized by low creatinine clearance, high plasma creatinine and urea levels, increased urinary excretion of proteins, glucose and AKI markers such as N-acetyl-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 and T-gelsolin, increased kidney levels of CD-68, iNOS, IL 1beta and TNF-alpha, and markedly higher histological renal damage and leukocyte infiltration than the CONT and CT-1 groups. Administration of CT-1 together with G reduced almost all of the above-described manifestations of G-induced AKI. The results of this study have potential clinical application, as CT-1 is near to being used as a drug for organ protection. PMID- 26996881 TI - A strategy for sequence control in vinyl polymers via iterative controlled radical cyclization. AB - There is a growing interest in sequence-controlled polymers toward advanced functional materials. However, control of side-chain order for vinyl polymers has been lacking feasibility in the field of polymer synthesis because of the inherent feature of chain-growth propagation. Here we show a general and versatile strategy to control sequence in vinyl polymers through iterative radical cyclization with orthogonally cleavable and renewable bonds. The proposed methodology employs a repetitive and iterative intramolecular cyclization via a radical intermediate in a one-time template with a radical-generating site at one end and an alkene end at the other, each of which is connected to a linker via independently cleavable and renewable bonds. The unique design specifically allowed control of radical addition reaction although inherent chain-growth intermediate (radical species) was used, as well as the iterative cycle and functionalization for resultant side chains, to lead to sequence-controlled vinyl polymers (or oligomers). PMID- 26996882 TI - Colorectal Cancer Screening Quality Measures: Beyond Colonoscopy. PMID- 26996883 TI - The controlled synthesis of polyglucose in one-dimensional coordination nanochannels. AB - We demonstrate a feasible method for the preparation of polyglucose (PGlc) with controlled structures, where the polymerization of glucose monomers was performed using one-dimensional nanochannels of [La(1,3,5-benzenetrisbenzoate)(H2O)]n (1). Cationic ring-opening polymerization of 1,6-anhydro-beta-D-glucose (levoglucosan) using 1 gave a quasi-linear PGlc, which contrasts highly with the results obtained from conventional polymerizations in bulk and solution. The regulated structure of PGlc prepared using the PCP led to a remarkable improvement in the processability and thermal stability of PGlc, which is useful in applications as a bioplastic. PMID- 26996884 TI - Porous MoO2 Nanosheets as Non-noble Bifunctional Electrocatalysts for Overall Water Splitting. AB - A porous MoO2 nanosheet as an active and stable bifunctional electrocatalyst for overall water splitting, is presented. It needs a cell voltage of only about 1.53 V to achieve a current density of 10 mA cm(-2) and maintains its activity for at least 24 h in a two-electrode configuration. PMID- 26996886 TI - Corrigendum. PMID- 26996885 TI - Barcelona conference on epigenetics and cancer 2015: Coding and non-coding functions of the genome. AB - The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled "Coding and Non-Coding functions of the Genome" took place October 29-30, 2015 in Barcelona. The 2015 BCEC was the third edition of a series of annual conferences jointly organized by 5 leading research centers in Barcelona together with B-Debate, an initiative of BioCat. Luciano Di Croce from the Center for Genomic Regulation and Marcus Buschbeck from the Josep Carreras Leukemia Research Institute put together the scientific program with a particular focus on the role of non-coding RNAs in enhancer regulation, epigenetic control by Polycomb complexes, histone variants, and nuclear organization. In one and a half days, 22 talks and 56 posters were presented to an audience of 215 participants. PMID- 26996887 TI - Cryopreservation method affects DNA fragmentation in trophectoderm and the speed of re-expansion in bovine blastocysts. AB - This study investigated re-expansion dynamics during culture of bovine blastocysts cryopreserved either by slow-freezing or vitrification. Also, the extent and localization of membrane damage and DNA fragmentation in re-expanded embryos were studied. Frozen-thawed embryos showed a significantly lower re expansion rate during 24 h of post-thawing culture compared to vitrified embryos. Vitrified embryos reached the maximum level of re-expansion rate by 12 h of culture whereas frozen embryos showed a gradual increase in re-expansion rate by 24 h of culture. When assayed by Hoechst/propidium iodide staining there was no difference in the numbers and ratio of membrane damaged cells between re-expanded frozen and vitrified embryos; however, the extent of membrane damage in blastomeres was significantly higher in both groups compared with non cryopreserved embryos (control). TUNEL assay combined with differential ICM and TE staining revealed a significantly higher number and ratio of TE cells showing DNA-fragmentation in frozen-thawed re-expanded blastocysts compared to vitrified ones; however, vitrification also resulted in an increased extent of DNA fragmentation in TE cells compared with control blastocysts. In frozen-thawed blastocysts increased extent of DNA fragmentation was associated with reduced numbers and proportion of TE cells compared with vitrified and control embryos. The number and ratio of ICM cells and the extent of DNA fragmentation in ICM did not differ among control, frozen and vitrified groups. In conclusion, compared with vitrified embryos, blastocysts preserved by slow-freezing showed a delayed timing of re-expansion which was associated with an increased frequency of DNA fragmentation in TE cells. PMID- 26996888 TI - Author Reply. PMID- 26996889 TI - Editorial Comment. PMID- 26996890 TI - The combined effects of noncontingent reinforcement and punishment on the reduction of rumination. AB - The current study extends the literature on the assessment and treatment of rumination through the evaluation of a combined reinforcement- and punishment based intervention. The study included a single participant with a history of rumination maintained by automatic reinforcement, as identified via a functional analysis. Both noncontingent reinforcement (NCR) with preferred edible items and punishment, in the form of a facial screen, were implemented separately to evaluate their independent effects on the occurrence of rumination. The final treatment package included both NCR and punishment procedures. Implementation of the combined treatment resulted in a 96.5% reduction in rumination relative to baseline. Procedural modifications and integrity errors also were evaluated. PMID- 26996891 TI - Bingel-Hirsch reaction mechanisms on TiSc2N@Ih-C80: the role of endohedral titanium nitride. AB - Recently, two unconventional singly bonded monoadducts of mixed-metal nitride clusterfullerene TiSc2N@Ih-C80 have been synthesized. Herein, the site selectivity and kinetic processes of Bingel-Hirsch reactions are explored by density functional theory calculations. Because of the rotation of the inner TiSc2N unit, two different types of singly bonded monoadducts (named 666 and 566 adducts) are clarified. Meanwhile, the two functionalized sites are situated above the Ti-Sc edge of the inner cluster in singly bonded adducts. Addition on the triple-fused-hexagon site (6-6-6 site) is found to be kinetically preferred, which can be attributed to the more positive charge of the carbon in the 6-6-6 site. In addition, we investigated the formation process of two conventional cycloadducts. A preference for the addition on the bridged hexagon-hexagon bond is concluded in theory, furthermore, one Sc atom instead of the Ti atom is pointing to the functionalized bond for the lowest-energy orientational product. PMID- 26996893 TI - Rational syntheses of helical pi-conjugated oligopyrrins with a bipyrrole linkage: geometry control of bis-copper(II) coordination. AB - A rational and effective approach for synthesizing linear pi-conjugated hexa-, hepta- and octapyrrins through the regioselective oxidative coupling of monoacylated tripyrrane and bilane is described. Depending upon the numbers of pyrrolic units, the geometry and properties of bis-copper(II) complexes could be systematically modulated. PMID- 26996892 TI - Hxt13, Hxt15, Hxt16 and Hxt17 from Saccharomyces cerevisiae represent a novel type of polyol transporters. AB - The genome of S. cerevisae encodes at least twenty hexose transporter-like proteins. Despite extensive research, the functions of Hxt8-Hxt17 have remained poorly defined. Here, we show that Hxt13, Hxt15, Hxt16 and Hxt17 transport two major hexitols in nature, mannitol and sorbitol, with moderate affinities, by a facilitative mechanism. Moreover, Hxt11 and Hxt15 are capable of transporting xylitol, a five-carbon polyol derived from xylose, the most abundant pentose in lignocellulosic biomass. Hxt11, Hxt13, Hxt15, Hxt16 and Hxt17 are phylogenetically and functionally distinct from known polyol transporters. Based on docking of polyols to homology models of transporters, we propose the architecture of their active site. In addition, we determined the kinetic parameters of mannitol and sorbitol dehydrogenases encoded in the yeast genome, showing that they discriminate between mannitol and sorbitol to a much higher degree than the transporters. PMID- 26996895 TI - [Management of secondary lymphedema in patients with cancer]. AB - Due to the increased number of cancer patients and the progress in cancer treatment, there are more cases with cancer-related lymphedema. Lymphedema treatment became part of oncological patients' care. Basic therapy for lymphedema is the complex decongestive therapy, which should be embedded into the patient's comprehensive medical care and should always be determined individually. Results of therapy are influenced by the experience of the doctor and the physiotherapist in lymphedema care, patient's complience, tumor behavior and the accompanying diseases. Lymphedema is a chronic disease, requires lifelong follow-up and treatment. For prevention and better care, it would be important to inform patients about lymphedema risk and appropriate life-style (e.g. weight control) preoperatively and during oncological follow-up. Early diagnosis is important. Lymphedema treatment should be integrated into palliative programmes. If therapy is started in time, complications may be avoided, healthcare costs may be reduced and better quality of life may be achieved. PMID- 26996894 TI - [Asymmetric dimethylarginine: predictor of cardiovascular diseases?]. AB - Cardiovascular diseases are the most common diseases worldwide. They are responsible for one third of global deaths and they are the leading cause of disability, too. The usage of different levels of prevention in combination with effective risk assessment improved these statistical data. Risk assessment based on classic risk factors has recently been supported with several new markers, such as asymmetric dimethylarginine, which is an endogenous competitive inhibitor of nitric oxide synthase. Elevated levels of asymmetric dimethylarginine have been reported in obese, smoker, hypercholesterolemic, hypertensive and diabetic patients. According to previous studies, asymmetric dimethylarginine is a suitable indicator of endothelial dysfunction, which is held to be the preceding condition before atherosclerosis. Several researches found positive correlation between higher levels of asymmetric dimethylarginine and coronary artery disease onset, or progression of existing coronary disease. According to a study involving 3000 patients, asymmetric dimethylarginine is an independent risk factor of cardiovascular mortality in patients with coronary artery disease. This article summarizes the role of asymmetric dimethylarginine in prediction of cardiovascular diseases, and underlines its importance in cardiovascular prevention. PMID- 26996896 TI - [Brugada phenocopy]. AB - Brugada phenocopies are clinical entities that are different from the true Brugada syndrome which is a channelopathy. Brugada phenocopy has reversible underlying conditions and, if underlying conditions resolve, the ECG pattern disappears. In this paper the author reviews and illustrates the known Brugada phenocopies. The most important etiologic categories of Brugada phenocopy include metabolic abnormalities (most commonly hyperkalemia), myocardial infarction, pulmonary embolism (massive), right ventricular mechanical compression, and others. The most important clinical issue is the different treatment of the Brugada syndrome and phenocopies in order to prevent cardiac death. In Brugada syndrome the implantable cardioverter defibrillator is the only effective treatment, while in Brugada phenocopies early, etiology-specific treatment can prevent cardiac death. PMID- 26996897 TI - [Treatment of recurrent glioblastoma with single-agent bevacizumab]. AB - INTRODUCTION: The prognosis of patients with recurrent glioblastoma is poor, as the median survival does not exceed 6 months. AIM: The aim of this study was to evaluate the efficacy of bevacizumab monotherapy in patients with recurrent glioblastoma multiforme. METHOD: From April, 2012 to June, 2015, 40 patients with recurrent glioblastoma multiforme were treated with bevacizumab in a dose of 10 mg/kg every 2 weeks. RESULTS: The average progression-free survival was 6.4 months (2-22 months), and the 6-month progression-free survival was 42.5%. The six-month overall survival was 82.5%, which corresponds to those published in the literature. CONCLUSIONS: Bevacizumab monotherapy improves progression-free survival in patients with recurrent glioblastoma multiforme. PMID- 26996898 TI - [Improvement of the reliability of the cause of death diagnoses by co-operation of public health authorities and the Central Statistical Office in Hungary]. AB - INTRODUCTION: The diagnosis of cause of death is based on the sequence of diagnoses declared by the physician who completes the death certificate that is processed by Central Statistical Office in Hungary. The validity control of the data requires the active involvement of the public health authority. AIM: The authors analyzed the death certificates from Tolna county in order to elaborate and evaluate methods for cause of death data validity control. METHOD: Diagnoses of cause of death declared by the physician, corrected by the social statistical review in the Central Statistical Office, and revised by public health authority were compared to evaluate the quality of cause of death data. RESULTS: It was found that 5-10% of the cause of death diagnoses declared by physicians required some modification, resulting more than 1% change in county specific mortality statistics of the main International Classification of Diseases groups. Physicians who reported inaccurate cause of death data were identified. 10 indicators were defined to monitor the process elaborated in the project. CONCLUSIONS: Co-operation between the Central Statistical Office and public health authorities to improve the quality of cause of death data should be continued because evaluation of public health interventions needs more and more reliable and detailed cause of death statistics. PMID- 26996899 TI - [Equally or equitably? Author roles and co-author shares in scientific publication]. AB - In the last decades the share of co-authored and, particularly, multi-authored papers has increased immensely. The paper deals with the causes and consequences of this phenomenon, specifically with those connected with scientometric analyses. Possibilities for fractional count of publications and citations, as well as problems of interpreting h-index and self-citation in case of multi authored papers are focused upon. PMID- 26996901 TI - Non-invasive expandable prosthesis in musculoskeletal oncology paediatric patients for the distal and proximal femur. First results. AB - PURPOSE: The non-invasive expandable prosthesis for skeletally immature patients is used after limb salvage surgery following tumor resection. The aim of the study was to assess the effectiveness of this treatment. METHODS: Seven paediatric patients with femoral tumors had resection and limb salvage with an uncemented non-invasive growing prosthesis. Mean age at the time of surgery was 9.8 (range 8-12) years. There were six distal femur osteosarcomas and one proximal femur Ewing sarcoma. Six total knee prosthesis were implanted at the time of primary tumor resection and one bipolar hip prosthesis was a revision from a failed osteoarticular hip allograft. Functional outcomes and emotional acceptance were assessed using the MSTS score. RESULTS: The mean follow-up was 65.3 months (range 29-91) months. Two patients died of pulmonary metastasis and there was no local recurrence. The mean femoral resection was 18 cm (range 17-19) on the knee, and 24 cm on the hip. Mean total expansion was 36.4 mm (range 12.3 63.5). The mean MSTS score after rehabilitation was 26.3 (range 21-29). There was one lengthening device failure, one late infection and one patient who required iliofemoral bypass grafting surgery for a pelvic metastasis. No local recurrence occurred. CONCLUSIONS: The non-invasive expandable prosthesis reduces the final limb-length discrepancy in growing patients with an acceptable function and appears to have an advantage as compared to invasive expandable prostheses which require multiple surgical procedures, but the complications rate is still high. PMID- 26996902 TI - Expression of C-X-C chemokine receptor type 7 in otorhinolaryngologic neoplasms. AB - INTRODUCTION: C-X-C chemokine receptor type 7 (CXCR7) has recently been characterised as a novel receptor for the C-X-C motif chemokine 12 (CXCL12)/stromal cell-derived factor 1-alpha. CXCR7 has been thought to play an important role in the pathogenesis of chronic rhinosinusitis, angiogenesis and tumour metastasis. The present study aimed to examine the expression of CXCR7 in tissue samples of laryngeal cancer and maxillary sinus carcinoma to determine its role in the development of otorhinolaryngologic neoplasms. METHODS: Samples of otorhinolaryngologic neoplasms were obtained from 17 patients with either nasal polyps (n = 7), laryngeal cancer (n = 5) or maxillary sinus carcinoma (n = 5), and who underwent surgical resection at West China Hospital of Sichuan University. Total RNA was isolated and CXCR7 mRNA expression was examined and quantified by relative real-time reverse transcription polymerase chain reaction. A one-way analysis of variance was performed using SPSS Statistics version 11.0 (SPSS Inc, Chicago, IL, USA) to compare the CXCR7 mRNA levels among the three groups of patients. RESULTS: All samples tested positive for CXCR7 mRNA. The quantitative results showed that the CXCR7 mRNA levels were highest in laryngeal cancer and lowest in maxillary sinus carcinoma neoplasms, although there was no significant difference among the three samples. CONCLUSION: CXCL12 and its receptor CXCR7 may contribute to eosinophilic inflammation in patients with chronic sinusitis and nasal polyps. Our results also suggest that CXCR7 may play a role in the progression, metastasis and angiogenesis of otorhinolaryngologic tumours. PMID- 26996903 TI - Antioxidant enzymes status and reproductive health of adult male workers exposed to brick kiln pollutants in Pakistan. AB - The present study was designed to study the effect of brick kilns emissions on the reproductive health and biochemical status of brick kiln workers and people living in the area near brick kilns. Body mass index (BMI) was significantly reduced in brick makers, carriers, and bakers compared to the control. Red blood cells count and hematocrit (%) were significantly high in brick bakers while MCH was significantly reduced in brick makers and brick bakers. Heavy metals (lead, cadmium, and chromium) concentration in whole blood of the brick kiln workers were significantly higher as compared to the control. Antioxidant enzymes (CAT, SOD, POD, GSH, and GR) were significantly reduced in brick kiln workers as compared to the control while TBARS level were significantly high in brick bakers as compared to the control. Plasma leutinizing hormone (LH) was significantly high in brick bakers while testosterone concentrations were significantly reduced in brick makers, carriers, and bakers. The present study shows that brick kiln workers and people living in the brick kiln vicinity are exposed to heavy metals and other pollutants that is a serious threat to their health. Alternate technology is needed to be developed and brick kilns should be replaced. PMID- 26996905 TI - Geochemistry and environmental threats of soils surrounding an abandoned mercury mine. AB - The closure of mercury mining areas is generally associated with a release of Hg and other metals into the environment due to the abandonment of mining wastes. Because of their potential toxic properties, the mobilization of particulate and soluble metal species is of major concern. In the present study, the environmental risks posed by soils surrounding an abandoned mercury mining area in Valle del Azogue (Almeria, Spain) are assessed through the determination of physical-chemical parameters, the quantification of metal concentrations, and the application of aquatic and terrestrial ecotoxicity bioassays. Chemical analysis of soil samples revealed concentrations of Hg, As, Ba, Pb, Sb, and Zn above international intervention values. Results from terrestrial tests showed detrimental effects in all studied organisms (Eisenia foetida, Folsomia candida, and different plant species) and revealed the avoidance response of earthworms as the most sensitive endpoint. Surprisingly, the most toxic samples were not the ones with higher metal contents but the ones presenting higher electrical conductivity. Aquatic ecotoxicity tests with Vibrio fischeri, Raphidocelis subcapitata, Daphnia magna, and Danio rerio were in accordance with terrestrial tests, confirming the need to couple environmental chemistry with ecotoxicological tools for the proper assessment of metal-contaminated sites. In view of the results, a remediative intervention of the studied area is recommended. PMID- 26996907 TI - Analysis of sulfonamides in soil, sediment, and sludge based on dynamic microwave assisted micellar extraction. AB - A green and high-throughput analytical method was described for the simultaneous determination of ten sulfonamides (SAs) from soil, sediment, and sludge in northeast China. None of potentially hazardous organic solvents was used in the whole sample preparation procedure, and the total preparation time of 15 samples was about 18 min. The limits of detection for the SAs were in the range of 0.42 0.68 ng g(-1). The intra-day and inter-day precisions, expressed by the relative standard deviation, were below 7 %. Under the optimum conditions, the recoveries of ten SAs were between 69.7 and 102.7 %. The proposed method was successfully applied to analyze the SAs residues in agricultural soils, river sediments, and sewage sludge. SAs were found at the levels of 1.40-2.31 ng g(-1) and 3.77-29.29 ng g(-1) in the sediments and sludge, respectively. The aging effect of spiked soil samples on the SAs recoveries was examined, and the results demonstrate that eight SAs could persist in five soils for 3 months. Compared with the traditional method, the proposed method could reduce the consumption of the organic solvent, shorten the sample preparation time, and increase the sample throughput. PMID- 26996904 TI - Cadmium stress in rice: toxic effects, tolerance mechanisms, and management: a critical review. AB - Cadmium (Cd) is one of the main pollutants in paddy fields, and its accumulation in rice (Oryza sativa L.) and subsequent transfer to food chain is a global environmental issue. This paper reviews the toxic effects, tolerance mechanisms, and management of Cd in a rice paddy. Cadmium toxicity decreases seed germination, growth, mineral nutrients, photosynthesis, and grain yield. It also causes oxidative stress and genotoxicity in rice. Plant response to Cd toxicity varies with cultivars, growth condition, and duration of Cd exposure. Under Cd stress, stimulation of antioxidant defense system, osmoregulation, ion homeostasis, and over production of signaling molecules are important tolerance mechanisms in rice. Several strategies have been proposed for the management of Cd-contaminated paddy soils. One such approach is the exogenous application of hormones, osmolytes, and signaling molecules. Moreover, Cd uptake and toxicity in rice can be decreased by proper application of essential nutrients such as nitrogen, zinc, iron, and selenium in Cd-contaminated soils. In addition, several inorganic (liming and silicon) and organic (compost and biochar) amendments have been applied in the soils to reduce Cd stress in rice. Selection of low Cd accumulating rice cultivars, crop rotation, water management, and exogenous application of microbes could be a reasonable approach to alleviate Cd toxicity in rice. To draw a sound conclusion, long-term field trials are still required, including risks and benefit analysis for various management strategies. PMID- 26996908 TI - The effect of anaerobic-aerobic and feast-famine cultivation pattern on bacterial diversity during poly-beta-hydroxybutyrate production from domestic sewage sludge. AB - The main objective of this work was to investigate the influence of different oxygen supply patterns on poly-beta-hydroxybutyrate (PHB) yield and bacterial community diversity. The anaerobic-aerobic (A/O) sequencing batch reactors (SBR1) and feast-famine (F/F) SBR2 were used to cultivate activated sludge to produce PHB. The mixed microbial communities were collected and analyzed after 3 months cultivation. The PHB maximum yield was 64 wt% in SBR1 and 53 wt% in SBR2. Pyrosequencing analysis 16S rRNA gene of two microbial communities indicated there were nine and four bacterial phyla in SBR1 and SBR2, respectively. Specifically, Proteobacteria (36.4 % of the total bacterial community), Actinobacteria (19.7 %), Acidobacteria (14.1 %), Firmicutes (4.4 %), Bacteroidetes (1.7 %), Cyanobacteria/Chloroplast (1.5 %), TM7 (0.8 %), Gemmatimonadetes (0.2 %), and Nitrospirae (0.1 %) were present in SBR1. Proteobacteria (94.2 %), Bacteroidetes (2.9 %), Firmicutes (1.9 %), and Actinobacteria (0.7 %) were present in SBR2. Our results indicated the SBR1 fermentation system was more stable than that of SBR2 for PHB accumulation. PMID- 26996909 TI - Adsorption of Cd(II) by two variable-charge soils in the presence of pectin. AB - Batch experiments were conducted to investigate cadmium(II) (Cd(II)) adsorption by two variable-charge soils (an Oxisol and an Ultisol) as influenced by the presence of pectin. When pectin dosage was less than 30 g kg(-1), the increase in Cd(II) adsorption with the increasing dose of pectin was greater than that when the pectin dosage was >30 g kg(-1). Although both Langmuir and Freundlich equations fitted the adsorption isotherms of Cd(II) and electrostatic adsorption data of Cd(II) by the two soils well, the Langmuir equation showed a better fit. The increase in the maximum total adsorption of Cd(II) induced by pectin was almost equal in both the soils, whereas the increase in the maximum electrostatic adsorption of Cd(II) was greater in the Oxisol than in the Ultisol because the former contained greater amounts of free Fe/Al oxides than the latter, which, in turn, led to a greater increase in the negative charge on the Oxisol. Therefore, the presence of pectin induced the increase in Cd(II) adsorption by the variable charge soils mainly through the electrostatic mechanism. Pectin increased the adsorption of Cd(II) by the variable-charge soils and thus decreased the activity and mobility of Cd(II) in these soils. PMID- 26996906 TI - Application of liquid chromatography-tandem mass spectrometry in quantitative bioanalyses of organic molecules in aquatic environment and organisms. AB - Analytical methods using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of metabolites or contaminants (or both) in various tissues of aquatic organisms and in the aquatic environment have received increasing attention in the last few years. This review discusses the findings relevant to such procedures published between 2005 and 2015. The aim is to evaluate the advantages, restrictions, and performances of the procedures from sample preparation to mass spectrometry measurement. To support these discussions, a general knowledge on LC-MS/MS is also provided. PMID- 26996910 TI - Effects of extraction methods and factors on leaching of metals from recycled concrete aggregates. AB - Leaching of metals (calcium (Ca), chromium (Cr), copper, (Cu), iron (Fe), and zinc (Zn)) of recycled concrete aggregates (RCAs) were investigated with four different leachate extraction methods (batch water leach tests (WLTs), toxicity leaching procedure test (TCLP), synthetic precipitation leaching procedure test (SPLP), and pH-dependent leach tests). WLTs were also used to perform a parametric study to evaluate factors including (i) effects of reaction time, (ii) atmosphere, (iii) liquid-to-solid (L/S) ratio, and (iv) particle size of RCA. The results from WLTs showed that reaction time and exposure to atmosphere had impact on leaching behavior of metals. An increase in L/S ratio decreased the effluent pH and all metal concentrations. Particle size of the RCA had impact on some metals but not all. Comparison of the leached concentrations of metals from select RCA samples with WLT method to leached concentrations from TCLP and SPLP methods revealed significant differences. For the same RCA samples, the highest metal concentrations were obtained with TCLP method, followed by WLT and SPLP methods. However, in all tests, the concentrations of all four (Cr, Cu, Fe, and Zn) metals were below the regulatory limits determined by EPA MCLs in all tests with few exceptions. pH-dependent batch water leach tests revealed that leaching pattern for Ca is more cationic whereas for other metals showed more amphoteric. The results obtained from the pH-dependent tests were evaluated with geochemical modeling (MINTEQA2) to estimate the governing leaching mechanisms for different metals. The results indicated that the releases of the elements were solubility controlled except Cr. PMID- 26996911 TI - Investigating the removal of some pharmaceutical compounds in hospital wastewater treatment plants operating in Saudi Arabia. AB - The concentrations of 12 pharmaceutical compounds (atenolol, erythromycin, cyclophosphamide, paracetamol, bezafibrate, carbamazepine, ciprofloxacin, caffeine, clarithromycin, lidocaine, sulfamethoxazole and N-acetylsulfamethoxazol (NACS)) were investigated in the influents and effluents of two hospital wastewater treatment plants (HWWTPs) in Saudi Arabia. The majority of the target analytes were detected in the influent samples apart from bezafibrate, cyclophosphamide, and erythromycin. Caffeine and paracetamol were detected in the influent at particularly high concentrations up to 75 and 12 ug/L, respectively. High removal efficiencies of the pharmaceutical compounds were observed in both HWWTPs, with greater than 90 % removal on average. Paracetamol, sulfamethoxazole, NACS, ciprofloxacin, and caffeine were eliminated by between >95 and >99 % on average. Atenolol, carbamazepine, and clarithromycin were eliminated by >86 % on average. Of particular interest were the high removal efficiencies of carbamazepine and antibiotics that were achieved by the HWWTPs; these compounds have been reported to be relatively recalcitrant to biological treatment and are generally only partially removed. Elevated temperatures and high levels of sunlight were considered to be the main factors that enhanced the removal of these compounds. PMID- 26996912 TI - Benchmarking the scientific output of industrial wastewater research in Arab world by utilizing bibliometric techniques. AB - Rapid population growth, worsening of the climate, and severity of freshwater scarcity are global challenges. In Arab world countries, where water resources are becoming increasingly scarce, the recycling of industrial wastewater could improve the efficiency of freshwater use. The benchmarking of scientific output of industrial wastewater research in the Arab world is an initiative that could support in shaping up and improving future research activities. This study assesses the scientific output of industrial wastewater research in the Arab world. A total of 2032 documents related to industrial wastewater were retrieved from 152 journals indexed in the Scopus databases; this represents 3.6 % of the global research output. The h-index of the retrieved documents was 70. The total number of citations, at the time of data analysis, was 34,296 with an average citation of 16.88 per document. Egypt, with a total publications of 655 (32.2 %), was ranked the first among the Arab countries followed by Saudi Arabia 300 (14.7 %) and Tunisia 297 (14.6 %). Egypt also had the highest h-index, assumed with Saudi Arabia, the first place in collaboration with other countries. Seven hundred fifteen (35.2 %) documents with 66 countries in Arab/non-Arab country collaborations were identified. Arab researchers collaborated mostly with researchers from France 239 (11.7 %), followed by the USA 127 (6.2 %). The top active journal was Desalination 126 (6.2 %), and the most productive institution was the National Research Center, Egypt 169 (8.3 %), followed by the King Abdul Aziz University, Saudi Arabia 75 (3.7 %). Environmental Science was the most prevalent field of interest 930 (45.8 %). Despite the promising indicators, there is a need to close the gap in research between the Arab world and the other nations. Optimizing the investments and developing regional experiences are key factors to promote the scientific research. PMID- 26996913 TI - Albendazole in environment: faecal concentrations in lambs and impact on lower development stages of helminths and seed germination. AB - Albendazole (ABZ), widely used benzimidazole anthelmintic, administered to animals enters via excrements into environment and may impact non-target organisms. Moreover, exposure of lower development stages of helminths to anthelmintics may also encourage the development of drug-resistant strains of helminths. In present project, the kinetics of ABZ (10 mg kg(-1) p.o.) and its metabolite (ABZ.SO, ABZSO2) elimination in faeces from treated Texel lambs were studied using UHPLC/MS/MS with the aim to find out their concentrations achievable in the environment. Consequently, the effect of these compounds on lower development stages of Barber's pole worm (Haemonchus contortus) and on germination of white mustard (Sinapis alba) seeds was evaluated. The results showed that ABZ concentrations in faeces excreted in 4-60 h after treatment were above the concentrations lethal for H. contortus eggs. Moreover, pre-incubation with sub-lethal doses of ABZ and ABZ.SO did not increase the resistance of H. contortus eggs and larvae to anthelmintics. On the other hand, concentrations of ABZ and ABZ.SO in faeces are so high that might have negative influence on non target soil invertebrates. As neither ABZ nor its metabolites affect the germination of mustard seeds, phytoremediation could be considered as potential tool for detoxification of ABZ in the environment. PMID- 26996914 TI - Physiological and transcriptional responses of Nitrosomonas europaea to TiO2 and ZnO nanoparticles and their mixtures. AB - The short-term combined effects of two most extensively used nanoparticles (NPs) TiO2 NPs (n-TiO2) and ZnO NPs (n-ZnO) versus their individual cytotoxicities on a model ammonia-oxidizing bacterium, Nitrosomonas europaea, were investigated at both physiological and transcriptional levels. n-ZnO exerted more serious impairment effects on cell morphology, cell density, membrane integrity, and ammonia monooxygenase activity than n-TiO2. However, the co-existing n-TiO2 displayed a dose-dependent mitigation effect on n-ZnO cytotoxicity. Consistently, the n-TiO2 and n-ZnO mixture-impacted global transcriptional expression profile, obtained with the whole-genome microarray technique, was more comparable to the n TiO2-impacted one than that impacted by n-ZnO. The expressions of numerous genes associated with heavy metal scavenging, DNA repair, and oxidative stress response were less up-regulated under the binary impacts of NP mixture than n-ZnO. Moreover, only n-ZnO alone stimulated the up-regulations of heavy metal resistance genes, which further implied the capacity of co-existing n-TiO2 to alleviate n-ZnO cytotoxicity. In addition, the damage of cell membrane structures and the suppression of cell membrane biogenesis-related gene expressions under the influence of either individual NPs or their combinations strongly suggested that the interruption of cell membranes and the associated metabolic activities would probably be one of NPs' critical cytotoxicity mechanisms. PMID- 26996915 TI - 4-Nitrophenol induces activation of Nrf2 antioxidant pathway and apoptosis of the germ cells in rat testes. AB - The potential of 4-nitrophenol (PNP) to affect testicular function of rats was assessed by intratesticular injection (IT). The protective effects of phytosterin (PS) on PNP-induced injury were assessed. Rats were sacrificed on days 1, 3, and 7 after IT of PNP (0.1 M, 50 MUl). PNP induced hemorrhage in intertubular areas and denudation of germinal epithelium. The expression of caspase-3 and sperm abnormalities were significantly increased (P < 0.05). The concentrations of testosterone in serum were significantly increased (P < 0.05) on the 1st and 3rd day. PNP induced oxidative stress in testes, which manifested increased SOD, CAT, GSH-Px activities, and increases in MDA, GSH, H2O2 concentrations (P < 0.05). The Nrf2 antioxidant pathway was activated as indicated by increased expression of Nrf2, HO-1, and GCLC mRNA (P < 0.05). Moreover, supplementation with PS resulted in an amelioration of PNP-induced oxidative damage. These results suggest that PNP induced activation of Nrf2 antioxidant pathway and apoptosis of the germ cells. PMID- 26996916 TI - Keystone indices probabilistic species sensitivity distribution in the case of the derivation of water quality criteria for copper in Tai Lake. AB - An alternative method for species sensitivity distribution (SSD) that considers the interaction between species and the community importance is illustrated in this article. First, a food web based on the relationship between predator and prey was constructed, and the keystone indices of species were obtained based on the food web. Then, the probability density distribution of the sensitivity for each species was derived from all of the available endpoints of each species. Finally, the species sensitivity distribution for ecosystem was constructed by sampling a specific number of values from the probability density distribution of the sensitivity for each species. Data of copper toxicity to the aquatic organisms in Tai Lake were selected to derived site-specific water quality criteria (WQC). Ninety-seven endpoints of acute toxicity for 47 species and 188 endpoints of chronic toxicity for 29 species were included, and the acute and chronic WQC developed by keystone indices probabilistic species sensitivity distribution (K-PSSD) were 4.982 MUg/L and 0.965 MUg/L, respectively. Results showed that the aquatic organisms of Tai Lake might be underprotected. Compared with the SSD, the K-PSSD coped with the interactions between species, the community importance, and the intraspecies and interspecies variation more effectively and was better at depicting the tendency and information of raw data. The K-PSSD was especially applicable to site-specific WQC and provided an alternative or supplement to the SSD. PMID- 26996917 TI - Catalytic gasification of biomass (Miscanthus) enhanced by CO2 sorption. AB - The main objective of this work concerns the coupling of biomass gasification reaction and CO2 sorption. The study shows the feasibility to promote biomass steam gasification in a dense fluidized bed reactor with CO2 sorption to enhance tar removal and hydrogen production. It also proves the efficiency of CaO Ca12Al14O33/olivine bi-functional materials to reduce heavy tar production. Experiments have been carried out in a fluidized bed gasifier using steam as the fluidizing medium to improve hydrogen production. Bed materials consisting of CaO based oxide for CO2 sorption (CaO-Ca12Al14O33) deposited on olivine for tar reduction were synthesized, their structural and textural properties were characterized by Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), and temperature-programmed reduction (TPR) methods, and the determination of their sorption capacity and stability analyzed by thermogravimetric analysis (TGA). It appears that this CaO-Ca12Al14O33/olivine sorbent/catalyst presents a good CO2 sorption stability (for seven cycles of carbonation/decarbonation). Compared to olivine and Fe/olivine in a fixed bed reactor for steam reforming of toluene chosen as tar model compound, it shows a better hydrogen production rate and a lower CO2 selectivity due to its sorption on the CaO phase. In the biomass steam gasification, the use of CaO-Ca12Al14O33/olivine as bed material at 700 degrees C leads to a higher H2 production than olivine at 800 degrees C thanks to CO2 sorption. Similar tar concentration and lighter tar production (analyzed by HPLC/UV) are observed. At 700 degrees C, sorbent addition allows to halve tar content and to eliminate the heaviest tars. PMID- 26996918 TI - Sustainable treatment of different high-strength cheese whey wastewaters: an innovative approach for atmospheric CO2 mitigation and fertilizer production. AB - Raw cheese whey wastewater (CWW) has been treated by means of FeCl3 coagulation flocculation, NaOH precipitation, and Ca(OH)2 precipitation. Three different types of CWW were considered: without cheese whey recovery (CWW0), 60 % cheese whey recovery (CWW60), and 80 % cheese whey recovery (CWW80). Cheese whey recovery significantly influenced the characteristics of the wastewater to be treated: organic matter, solids, turbidity, conductivity, sodium, chloride, calcium, nitrogen, potassium, and phosphorus. Initial organic load was reduced to values in the interval of 60-70 %. Application of FeCl3, NaOH, or Ca(OH)2 involved additional chemical oxygen demand (COD) depletions regardless of the CWW used. Under optimum conditions, the combination of 80 % cheese whey recovery and lime application led to 90 % reduction in COD. Turbidity (99.8%), total suspended solids (TSS) (98-99 %), oils and fats (82-96 %), phosphorus (98-99 %), potassium (96-97 %), and total coliforms (100 %) were also reduced. Sludge generated in the latter process showed excellent settling properties. This solid after filtration and natural evaporation can be used as fertilizer with limitations due to its saline nature. In an innovative, low-cost, and environmentally friendly technology, supernatant coming from the Ca(OH)2 addition was naturally neutralized in 4-6 days by atmospheric CO2 absorption without reagent addition. Consequently, a final aerobic biodegradation step can be applied for effluent polishing. This technology also allows for some atmospheric CO2 mitigation. Time requirement for the natural carbonation depends on the effluent characteristics. A precipitate rich in organic matter and nutrients and depletions of solids, sodium, phosphorus, magnesium, Kjeldahl, and ammoniacal nitrogen were also achieved during the natural carbonation. PMID- 26996920 TI - Ruthenium(II)-Catalyzed Decarboxylative C-H Activation: Versatile Routes to meta Alkenylated Arenes. AB - Ruthenium(II) bis(carboxylate)s proved highly effective for two decarboxylative C H alkenylation strategies. The decarboxylation proceeded efficiently at rather low temperatures. The unique versatility of the decarboxylative ruthenium(II) catalysis is reflected in the oxidative olefinations with alkenes as well as the redox-neutral hydroarylations of alkynes. PMID- 26996919 TI - Nutrients, heavy metals and phthalate acid esters in solar greenhouse soils in Round-Bohai Bay-Region, China: impacts of cultivation year and biogeography. AB - Solar greenhouse is a common facility type used for horticultural crop production in China. However, most solar greenhouse fields have been degraded due to continuous cropping and excessive fertilizer use. Therefore, we investigated solar greenhouse soils covering a wide range of cultivation years and environmental conditions in Round-Bohai Bay-Region to test the effects of cultivation year and biogeography on nutrients, heavy metals, and phthalate acid esters (PAEs). In general, soil pH decreased while soil electrical conductivity (EC), organic matter (OM), total nitrogen (TN), NO3 (-)-N, NH4 (+)-N, mineral nitrogen (MN), Olsen-P, and NH4OAc-K contents increased as time of cultivation increased. However, this trend was influenced by sampling sites. Among sampling sites, Jiangsu showed a relatively low soil pH and high Olsen-P content, while Hebei showed a relatively high soil EC value, NO3 (-)-N, NH4 (+)-N, MN, and NH4OAc-K contents. Liaoning was characterized by relatively high soil OM and TN contents. The nutrient level indexes in evaluation of soil quality on Olsen-P and NH4OAc-K exceeded the standard seriously. The maximum values of the heavy metals Cd, Cu, and Zn were 4.87, 2.78, and 1.15 times higher than the threshold values, respectively. There was a rising trend on the heavy metal contents with the increasing cultivation years, and this trend was significantly influenced by sampling sites. Both Cu and Zn had relative high heavy metal indexes in evaluation of soil pollution. The PAEs were not detected in almost all sampling soils. Overall, the excessive fertilizer application was an important cause of nutrient accumulation and heavy metal pollution, resulting in soil degradation in solar greenhouses. PMID- 26996921 TI - Acyclic forms of aldohexoses and ketohexoses in aqueous and DMSO solutions: conformational features studied using molecular dynamics simulations. AB - The molecular properties of aldohexoses and ketohexoses are usually studied in the context of their cyclic, furanose or pyranose structures which is due to the abundance of related tautomeric forms in aqueous solution. We studied the conformational features of a complete series of D-aldohexoses (D-allose, D altrose, D-glucose, D-mannose, D-gulose, d-idose, D-galactose and D-talose) and D ketohexoses (D-psicose, D-fructose, D-sorbose and D-tagatose) as well as of L psicose by using microsecond-timescale molecular dynamics in explicit water and DMSO with the use of enhanced sampling methods. In each of the studied cases the preferred conformation corresponded to an extended chain structure; the less populated conformers included the quasi-cyclic structures, close to furanose rings and common for both aldo- and ketohexoses. The orientational preferences of the aldehyde or ketone groups are correlated with the relative populations of anomers characteristic of cyclic aldo- and ketohexoses, respectively, thus indicating that basic features of anomeric equilibria are preserved even if hexose molecules are not in their cyclic forms. No analogous relationship is observed in the case of other structural characteristics, such as the preferences of acyclic molecules to form either the furanose-or pyranose-like structures or maintaining the chair-like geometry of pseudo-pyranose rings. PMID- 26996923 TI - Use of AFIS for linking scenes of crime. AB - Forensic intelligence can provide critical information in criminal investigations - the linkage of crime scenes. The Automatic Fingerprint Identification System (AFIS) is an example of a technological improvement that has advanced the entire forensic identification field to strive for new goals and achievements. In one example using AFIS, a series of burglaries into private apartments enabled a fingerprint examiner to search latent prints from different burglary scenes against an unsolved latent print database. Latent finger and palm prints coming from the same source were associated with over than 20 cases. Then, by forensic intelligence and profile analysis the offender's behavior could be anticipated. He was caught, identified, and arrested. It is recommended to perform an AFIS search of LT/UL prints against current crimes automatically as part of laboratory protocol and not by an examiner's discretion. This approach may link different crime scenes. PMID- 26996922 TI - Skeletal light-scattering accelerates bleaching response in reef-building corals. AB - BACKGROUND: At the forefront of ecosystems adversely affected by climate change, coral reefs are sensitive to anomalously high temperatures which disassociate (bleaching) photosynthetic symbionts (Symbiodinium) from coral hosts and cause increasingly frequent and severe mass mortality events. Susceptibility to bleaching and mortality is variable among corals, and is determined by unknown proportions of environmental history and the synergy of Symbiodinium- and coral specific properties. Symbiodinium live within host tissues overlaying the coral skeleton, which increases light availability through multiple light-scattering, forming one of the most efficient biological collectors of solar radiation. Light transport in the upper ~200 MUm layer of corals skeletons (measured as 'microscopic' reduced-scattering coefficient, MU'(S,m)), has been identified as a determinant of excess light increase during bleaching and is therefore a potential determinant of the differential rate and severity of bleaching response among coral species. RESULTS: Here we experimentally demonstrate (in ten coral species) that, under thermal stress alone or combined thermal and light stress, low-MU'(S,m) corals bleach at higher rate and severity than high-MU'(S,m) corals and the Symbiodinium associated with low-MU'(S,m) corals experience twice the decrease in photochemical efficiency. We further modelled the light absorbed by Symbiodinium due to skeletal-scattering and show that the estimated skeleton dependent light absorbed by Symbiodinium (per unit of photosynthetic pigment) and the temporal rate of increase in absorbed light during bleaching are several fold higher in low-MU'(S,m) corals. CONCLUSIONS: While symbionts associated with low [Formula: see text] corals receive less total light from the skeleton, they experience a higher rate of light increase once bleaching is initiated and absorbing bodies are lost; further precipitating the bleaching response. Because microscopic skeletal light-scattering is a robust predictor of light-dependent bleaching among the corals assessed here, this work establishes MU'(S,m) as one of the key determinants of differential bleaching response. PMID- 26996925 TI - M-matrix based robust stability and stabilization for uncertain discrete-time switched TS fuzzy systems with time-varying delays. AB - This paper provides novel sufficient conditions on robust asymptotic stability and stabilization for a class of uncertain discrete-time switched fuzzy with time varying delays. The attention is focused on developing new algebraic criteria to break with classical criteria in terms of Linear Matrix Inequalities (LMIs). Firstly, based on the M-matrix proprieties and through l1,infinity induced norms notion, new delay-dependent sufficient conditions are derived to ensure the asymptotic stability and stabilization for a class of uncertain discrete-time switched fuzzy systems with time-varying delay. Secondly, these results are extended for a class of uncertain discrete-time switched fuzzy systems with time delays, modeled by difference equations. Finally, two numerical examples and practical example (a robot arm) are provided to demonstrate the advantage and the effectiveness of our results. PMID- 26996924 TI - Invited review: Activation of G proteins by GTP and the mechanism of Galpha catalyzed GTP hydrolysis. AB - This review addresses the regulatory consequences of the binding of GTP to the alpha subunits (Galpha) of heterotrimeric G proteins, the reaction mechanism of GTP hydrolysis catalyzed by Galpha and the means by which GTPase activating proteins (GAPs) stimulate the GTPase activity of Galpha. The high energy of GTP binding is used to restrain and stabilize the conformation of the Galpha switch segments, particularly switch II, to afford stable complementary to the surfaces of Galpha effectors, while excluding interaction with Gbetagamma, the regulatory binding partner of GDP-bound Galpha. Upon GTP hydrolysis, the energy of these conformational restraints is dissipated and the two switch segments, particularly switch II, become flexible and are able to adopt a conformation suitable for tight binding to Gbetagamma. Catalytic site pre-organization presents a significant activation energy barrier to Galpha GTPase activity. The glutamine residue near the N-terminus of switch II (Glncat ) must adopt a conformation in which it orients and stabilizes the gamma phosphate and the water nucleophile for an in-line attack. The transition state is probably loose with dissociative character; phosphoryl transfer may be concerted. The catalytic arginine in switch I (Argcat ), together with amide hydrogen bonds from the phosphate binding loop, stabilize charge at the beta-gamma bridge oxygen of the leaving group. GAPs that harbor "regulator of protein signaling" (RGS) domains, or structurally unrelated domains within G protein effectors that function as GAPs, accelerate catalysis by stabilizing the pre-transition state for Galpha-catalyzed GTP hydrolysis, primarily by restraining Argcat and Glncat to their catalytic conformations. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 449-462, 2016. PMID- 26996926 TI - PKCbeta Inhibitors Attenuate Amphetamine-Stimulated Dopamine Efflux. AB - Amphetamine abuse afflicts over 13 million people, and there is currently no universally accepted treatment for amphetamine addiction. Amphetamine serves as a substrate for the dopamine transporter and reverses the transporter to cause an increase in extracellular dopamine. Activation of the beta subunit of protein kinase C (PKCbeta) enhances extracellular dopamine in the presence of amphetamine by facilitating the reverse transport of dopamine and internalizing the D2 autoreceptor. We previously demonstrated that PKCbeta inhibitors block amphetamine-stimulated dopamine efflux in synaptosomes from rat striatum in vitro. In this study, we utilized in vivo microdialysis in live, behaving rats to assess the effect of the PKCbeta inhibitors, enzastaurin and ruboxistaurin, on amphetamine-stimulated locomotion and increases in monoamines and their metabolites. A 30 min perfusion of the nucleus accumbens core with 1 MUM enzastaurin or 1 MUM ruboxistaurin reduced efflux of dopamine and its metabolite 3-methoxytyramine induced by amphetamine by approximately 50%. The inhibitors also significantly reduced amphetamine-stimulated extracellular levels of norepinephrine. The stimulation of locomotor behavior by amphetamine, measured simultaneously with the analytes, was comparably reduced by the PKCbeta inhibitors. Using a stable isotope label retrodialysis procedure, we determined that ruboxistaurin had no effect on basal levels of dopamine, norepinephrine, glutamate, or GABA. In addition, normal uptake function through the dopamine transporter was unaltered by the PKCbeta inhibitors, as measured in rat synaptosomes. Our results support the utility of using PKCbeta inhibitors to reduce the effects of amphetamine. PMID- 26996927 TI - The novel anti-CD19 chimeric antigen receptors with humanized scFv (single-chain variable fragment) trigger leukemia cell killing. AB - The molecular design of CARs (Chimeric Antigen Receptors), especially the scFv, has been a major part to use of CAR-T cells for targeted adoptive immunotherapy. To address this issue, we chose a vector backbone encoding a second-generation CAR based on efficacy of a murine scFv-based CAR. Next, we generated a panel of humanized scFvs and tested in vitro for their ability to direct CAR-T cells to specifically lyse, proliferate, and secrete cytokines in response to antigen bearing targets. Furthermore, in a xenograft model of lymphoma, human T cells expressing humanized scFvs exhibited the same anti-tumor efficacy as those expressing murine scFv and prolonged survival compared with cells expressing control CAR. Therefore, we uncovered CARs expressing humanized scFv domain that contribute the similar enhanced antileukemic efficacy and survival in tumor bearing mice. These results provide the basis for the future clinical studies of CAR-T cells transduced with humanized scFv directed to CD19. PMID- 26996928 TI - Analysis of the Abuse and Diversion of the Buprenorphine Transdermal Delivery System. AB - Prescription opioid abuse and diversion are major causes of morbidity and mortality in the United States. The buprenorphine transdermal delivery system (BTDS) is indicated for the treatment of moderate to severe chronic pain and provides a continuous dose of 5, 7.5, 10, 15, or 20 MUg/h buprenorphine for 7 days. Quarterly rates of abuse and diversion of BTDS were compared with 4 comparator groups: 1) other buprenorphine products, 2) fentanyl patches, 3) extended-release (ER) opioid tablets/capsules, and 4) ER tramadol. Data were obtained from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Treatment Programs Combined (Opioid Treatment and Survey of Key Informants' Patients Programs), and College Survey Programs. Rates were calculated using case counts per population and mentions per prescriptions filled. Poisson regression analysis was used to compare mean rates over time across drug groups after allowing for drug group specific dispersion parameters. Population adjusted abuse rates were low for BTDS in all of the RADARS System programs compared with the other comparator groups. Findings were similar for the prescription adjusted rates, with BTDS reported at the lowest rates in all programs. Route of abuse differed slightly for BTDS and the comparator groups depending on the program. BTDS was abused and diverted at low rates compared with the other opioid groups in 5 programs of the RADARS System using either population-based rates or prescription dispensed rates. PERSPECTIVE: Data from the RADARS System show the BTDS is abused and diverted at low rates compared with other opioid groups including other forms of buprenorphine, fentanyl patches, ER opioid formulations, and ER tramadol. PMID- 26996929 TI - Outcome, incidence and risk factors for stroke after pediatric heart transplantation: An analysis of the International Society for Heart and Lung Transplantation Registry. AB - BACKGROUND: In the registry of the International Society for Heart and Lung Transplantation (ISHLT), cerebrovascular accidents are the fifth most common cause for mortality after pediatric heart transplantation (PHTx), but details are lacking in the literature. The purpose of this analysis of the ISHLT registry was to determine the prevalence, risk factors and outcomes of stroke after PHTx. METHODS: Data from the ISHLT registry (1998 to 2010) were used to identify all patients whose primary transplantation was performed at <18 years of age. Of the 10,441 transplants reviewed, 9,837 primary transplants and 604 retransplants were analyzed. RESULTS: Three hundred thirty-three (3%) patients had a stroke after PHTx; 54% were male, median age at PHTx was 6 years (0 to 17 years), and 44% had a diagnosis of congenital heart disease (CHD). Freedom from stroke was 99% at 1 month, 97% at 5 years, 95% at 10 years and 91% at 20 years post-PHTx. After a stroke, survival at 1 month, 1 year and 5 years was 83%, 69% and 55%, respectively. Multivariable independent risk factors for stroke included a primary diagnosis of congenital heart disease [hazard ratio (HR) 1.4 (1.1 to 1.7), p = 0.01], previous stroke [HR 4.5 (3.2 to 6.2), p < 0.001], history of aborted sudden death [HR 1.5 (1.1 to 2), p = 0.01], ventricular assist device [HR 1.5 (1.1 to 2.2), p = 0.03] or extracorporeal membrane oxygenation [HR 1.7 (1.2 to 2.2), p = 0.01], post-operative dialysis [HR 3.3 (2.3 to 4.7), p < 0.001], infection requiring antibiotics before discharge [HR 1.9 (1.4 to 2.5), p < 0.001], pacemaker implantation [HR 1.6 (1 to 2.5), p = 0.04] or drug-treated hypertension [HR 1.4 (1.1 to 1.8), p = 0.003] during follow-up. CONCLUSIONS: Stroke after pediatric heart transplantation is associated with increased mortality. Congenital heart disease and mechanical support both portend greater risk, in addition to markers of increased pre- and post-transplant medical acuity. PMID- 26996931 TI - Nintedanib in restrictive chronic lung allograft dysfunction after lung transplantation. PMID- 26996930 TI - B cells in transplantation. AB - B cell responses underlie the most vexing immunological barriers to organ transplantation. Much has been learned about the molecular mechanisms of B cell responses to antigen and new therapeutic agents that specifically target B cells or suppress their functions are available. Yet, despite recent advances, there remains an incomplete understanding about how B cell functions determine the fate of organ transplants and how, whether or when potent new therapeutics should optimally be used. This gap in understanding reflects in part the realization that besides producing antibodies, B cells can also regulate cellular immunity, contribute to the genesis of tolerance and induce accommodation. Whether non specific depletion of B cells, their progeny or suppression of their functions would undermine these non-cognate functions and whether graft outcome would suffer as a result is unknown. These questions were discussed at a symposium on "B cells in transplantation" at the 2015 ISHLT annual meeting. Those discussions are summarized here and a new perspective is offered. PMID- 26996932 TI - A 5-year perspective on a removable overdenture appliance for a patient with osteonecrosis of the jaw, a mandibular resection, and rampant caries. AB - A 78-year-old man with a history osteonecrosis of the jaw and 2 subsequent surgeries to repair a fractured mandible had a condition that contraindicates most dentoalveolar procedures to restore his failing dentition. A Snap-On-Smile overdenture restored his opportunity for natural speech, occlusal function, and esthetics. PMID- 26996933 TI - Correction of cheek biting in a dentate patient. AB - Postsurgical injury by teeth to oral mucosa (reconstructed by a flap) can lead to ulceration and subsequent infection at the reconstructed site. A prompt intervention by fabricating a specially designed prosthesis to deflect the reconstruction flap away from the occluding teeth has been described for the treatment of cheek biting in the present clinical report. PMID- 26996934 TI - Effects of artificial aging conditions on yttria-stabilized zirconia implant abutments. AB - STATEMENT OF PROBLEM: Most ceramic abutments are fabricated from yttria stabilized tetragonal zirconia (Y-TZP). However, Y-TZP undergoes hydrothermal degradation, a process that is not well understood. PURPOSE: The purpose of this in vitro study was to assess the effects of artificial aging conditions on the fracture load, phase stability, and surface microstructure of a Y-TZP abutment. MATERIAL AND METHODS: Thirty-two prefabricated Y-TZP abutments were screwed and tightened down to external hexagon implants and divided into 4 groups (n = 8): C, control; MC, mechanical cycling (1*10(6) cycles; 10 Hz); AUT, autoclaving (134 degrees C; 5 hours; 0.2 MPa); and TC, thermal cycling (10(4) cycles; 5 degrees /55 degrees C). A single-load-to-fracture test was performed at a crosshead speed of 0.5 mm/min to assess the assembly's resistance to fracture (ISO Norm 14801). X ray diffraction (XRD) analysis was applied to observe and quantify the tetragonal monoclinic (t-m) phase transformation. Representative abutments were examined with high-resolution scanning electron microscopy (SEM) to observe the surface characteristics of the abutments. Load-to-fracture test results (N) were compared by ANOVA and Tukey test (alpha=.05). RESULTS: XRD measurements revealed the monoclinic phase in some abutments after each aging condition. All the aging conditions reduced the fracture load significantly (P<.001). Mechanical cycling reduced the fracture load more than autoclaving (P=.034). No differences were found in the process of surface degradation among the groups; however, the SEM detected grinding-induced surface flaws and microcracks. CONCLUSIONS: The resistance to fracture and the phase stability of Y-TZP implant abutments were susceptible to hydrothermal and mechanical conditions. The surface microstructure of Y-TZP abutments did not change after aging conditions. PMID- 26996935 TI - Entropic forces drive contraction of cytoskeletal networks. AB - The cytoskeleton is a network of interconnected protein filaments, which provide a three-dimensional scaffold for cells. Remodeling of the cytoskeleton is important for key cellular processes, such as cell motility, division, or morphogenesis. This remodeling is traditionally considered to be driven exclusively by processes consuming chemical energy, such as the dynamics of the filaments or the action of molecular motors. Here, we review two mechanisms of cytoskeletal network remodeling that are independent of the consumption of chemical energy. In both cases directed motion of overlapping filaments is driven by entropic forces, which arise from harnessing thermal energy present in solution. Entropic forces are induced either by macromolecular crowding agents or by diffusible crosslinkers confined to the regions where filaments overlap. Both mechanisms increase filament overlap length and lead to the contraction of filament networks. These force-generating mechanisms, together with the chemical energy-dependent mechanisms, need to be considered for the comprehensive quantitative picture of the remodeling of cytoskeletal networks in cells. PMID- 26996936 TI - Historical Records of Mercury Stable Isotopes in Sediments of Tibetan Lakes. AB - The Tibetan Plateau (TP), known as the "Third Pole", is a critical zone for atmospheric mercury (Hg) deposition. Increasing anthropogenic activities in the globe leads to environmental changes, which may affect the loading, transport and deposition of Hg in the environment. However, the deposition history and geochemical cycling of Hg in the TP is still uncertain. Our records of Hg and Hg isotopes in sediment profiles of the two largest lakes in the TP, Lake Qinghai and Nam Co, show increased Hg influx since last century, with the maximum Hg influx enrichment ratios of 5.4 and 3.5 in Lake Qinghai and Nam Co, respectively. Shifts in negative delta (202)Hg in Lake Qinghai (-4.55 to -3.150/00) and Nam Co (-5.04 to -2.160/00) indicate increased atmospheric Hg deposition through rainfall, vegetation and runoff of soils. Mass independent fractionation of both even-Hg (? (200)Hg: +0.05 to +0.100/00) and odd-Hg (? (199)Hg: +0.12 to +0.310/00) isotopes were observed. Positive Delta (200)Hg suggest high proportion of precipitation-derived Hg in the TP, whereas the positive Delta (199)Hg results from Hg(II) photo-reduction. Both lakes show increasing Delta (199)Hg since the 1900 s, and we conclude that with the decrease of ice duration, Hg(II) photo reduction may have been accelerated in these TP lakes. PMID- 26996937 TI - A unique hetero-hexadecameric architecture displayed by the Escherichia coli O157 PaaA2-ParE2 antitoxin-toxin complex. AB - Many bacterial pathogens modulate their metabolic activity, virulence and pathogenicity through so-called "toxin-antitoxin" (TA) modules. The genome of the human pathogen Escherichia coli O157 contains two three-component TA modules related to the known parDE module. Here, we show that the toxin EcParE2 maps in a branch of the RelE/ParE toxin superfamily that is distinct from the branches that contain verified gyrase and ribosome inhibitors. The structure of EcParE2 closely resembles that of Caulobacter crescentus ParE but shows a distinct pattern of conserved surface residues, in agreement with its apparent inability to interact with GyrA. The antitoxin EcPaaA2 is characterized by two alpha-helices (H1 and H2) that serve as molecular recognition elements to wrap itself around EcParE2. Both EcPaaA2 H1 and H2 are required to sustain a high-affinity interaction with EcParE2 and for the inhibition of EcParE2-mediated killing in vivo. Furthermore, evidence demonstrates that EcPaaA2 H2, but not H1, determines specificity for EcParE2. The initially formed EcPaaA2-EcParE2 heterodimer then assembles into a hetero-hexadecamer, which is stable in solution and is formed in a highly cooperative manner. Together these findings provide novel data on quaternary structure, TA interactions and activity of a hitherto poorly characterized family of TA modules. PMID- 26996938 TI - Molecular Mechanisms Regulating Stem Cells Fate. PMID- 26996940 TI - Regulation of Microtubule Assembly by Tau and not by Pin1. AB - The molecular mechanism by which the microtubule-associated protein (MAP) tau regulates the formation of microtubules (MTs) is poorly understood. The activity of tau is controlled via phosphorylation at specific Ser/Thr sites. Of those phosphorylation sites, 17 precede a proline, making them potential recognition sites for the peptidyl-prolyl isomerase Pin1. Pin1 binding and catalysis of phosphorylated tau at the AT180 epitope, which was implicated in Alzheimer's disease, has been reported to be crucial for restoring tau's ability to promote MT polymerization in vitro and in vivo [1]. Surprisingly, we discover that Pin1 does not promote phosphorylated tau-induced MT formation in vitro, refuting the commonly accepted model in which Pin1 binding and catalysis on the A180 epitope restores the function of the Alzheimer's associated phosphorylated tau in tubulin assembly [1, 2]. Using turbidity assays, time-resolved small angle X-ray scattering (SAXS), and time-resolved negative stain electron microscopy (EM), we investigate the mechanism of tau-mediated MT assembly and the role of the Thr231 and Ser235 phosphorylation on this process. We discover novel GTP-tubulin ring shaped species, which are detectable in the earliest stage of tau-induced polymerization and may play a crucial role in the early nucleation phase of MT assembly. Finally, by NMR and SAXS experiments, we show that the tau molecules must be located on the surface of MTs and tubulin rings during the polymerization reaction. The interaction between tau and tubulin is multipartite, with a high affinity interaction of the four tubulin-binding repeats, and a weaker interaction with the proline-rich sequence and the termini of tau. PMID- 26996941 TI - Molecular Mechanism of Pin1-Tau Recognition and Catalysis. AB - Human peptidyl-prolyl isomerase (PPIase) Pin1 plays key roles in developmental processes, cell proliferation, and neuronal function. Extensive phosphorylation of the microtubule binding protein tau has been implicated in neurodegeneration and Alzheimer's disease. For the past 15years, these two players have been the focus of an enormous research effort to unravel the biological relevance of their interplay in health and disease, resulting in a series of proposed molecular mechanism of how Pin1 catalysis of tau results in biological phenotypes. Our results presented here refute these mechanisms of Pin1 action. Using NMR, isothermal calorimetry (ITC), and small angle x-ray scattering (SAXS), we dissect binding and catalysis on multiple phosphorylated tau with particular emphasis toward the Alzheimer's associated AT180 tau epitope containing phosphorylated THR231 and SER235. We find that phosphorylated (p-) SER235-PRO, but not pTHR231 PRO, is exclusively catalyzed by full-length Pin1 and isolated PPIase domain. Importantly, site-specific measurements of Pin1-catalysis of CDK2/CycA phosphorylated full-length tau reveal a number of sites that are catalyzed simultaneously with different efficiencies. Furthermore, we show that the turnover efficiency at pSER235 by Pin1 is independent of both the WW domain and phosphorylation on THR231. Our mechanistic results on site-specific binding and catalysis together with the lack of an increase of dephosphorylation rates by PP2A counter a series of previously published models for the role of Pin1 catalysis of tau in Alzheimer's disease. Together, our data reemphasize the complicated scenario between binding and catalysis of multiple phosphorylated tau by Pin1 and the need for directly linking biological phenotypes and residue specific turnover in Pin1 substrates. PMID- 26996942 TI - Current Approaches in Computational Drug Resistance Prediction in HIV. AB - BACKGROUND: Today a broad range of antiretroviral drug regimens are applicable for the successful suppression of virus replication in human immunodeficiency virus (HIV) infected people. However, there still remains an obstacle in therapy: the high mutation rate of the HI virus under drug pressure leads to resistant variants causing failure of permanent and effective treatment. Therefore, resistance testing is therefore inevitable to administer appropriate antiviral drugs to infected patients. METHODS: By means of current high-throughput sequencing technologies, computational models have recently constituted important assistance in drug resistance prediction and can guide the choice of medical treatment. Several machine learning algorithms, e.g. support-vector machines, random forests, as well as statistical methods have been already applied to genotypic data and structural information to predict drug resistance. RESULTS: In this review, we provide an overview of existing approaches in computational drug resistance prediction in HIV. We further highlight the challenges and limitations of current methods, e.g. time complexity and prediction of non-B subtypes. CONCLUSION: Moreover, we give a perspective on multi-label and multi-instance classification techniques that potentially tackle the problem of cross resistances among drugs. PMID- 26996943 TI - Assessment of the Accuracy of Whole Blood/Serum Rapid Point-of-Care HIV Three Dot Test for Oral Fluid Specimens. AB - BACKGROUND: Saliva rapid point of care HIV tests have proven advantages over blood-based HIV tests in terms of quality, rapidity and convenience. AIM: To assess the sensitivity, specificity and reproducibility of saliva samples using the serum/ whole blood rapid test and to compare it with serum specimens. MATERIAL & METHODS: 52 seropositive and 52 seronegative patients were included in the study. Stimulated and unstimulated saliva samples were collected and tested using the serum/ whole blood signal HIV THREE DOT rapid test (span diagnostics). RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of the test was found to be 100% for saliva samples. CONCLUSION: Saliva samples can be used as a substitute to serum/whole blood for HIV testing. It can be done using the serum/whole blood kits which are cheaper and readily available thus broadening the reach of testing programs in resource limited settings. PMID- 26996939 TI - TIRF microscopy analysis of human Cof1, Cof2, and ADF effects on actin filament severing and turnover. AB - Dynamic remodeling and turnover of cellular actin networks requires actin filament severing by actin-depolymerizing factor (ADF)/Cofilin proteins. Mammals express three different ADF/Cofilins (Cof1, Cof2, and ADF), and genetic studies suggest that in vivo they perform both overlapping and unique functions. To gain mechanistic insights into their different roles, we directly compared their G actin and F-actin binding affinities, and quantified the actin filament severing activities of human Cof1, Cof2, and ADF using in vitro total internal reflection fluorescence microscopy. All three ADF/Cofilins had similar affinities for G actin and F-actin. However, Cof2 and ADF severed filaments much more efficiently than Cof1 at both lower and higher concentrations and using either muscle or platelet actin. Furthermore, Cof2 and ADF were more effective than Cof1 in promoting "enhanced disassembly" when combined with actin disassembly co-factors Coronin-1B and actin-interacting protein 1 (AIP1), and these differences were observed on both preformed and actively growing filaments. To probe the mechanism underlying these differences, we used multi-wavelength total internal reflection fluorescence microscopy to directly observe Cy3-Cof1 and Cy3-Cof2 interacting with actin filaments in real time during severing. Cof1 and Cof2 each bound to filaments with similar kinetics, yet Cof2 induced severing much more rapidly than Cof1, decreasing the time interval between initial binding on a filament and severing at the same location. These differences in ADF/Cofilin activities and mechanisms may be used in cells to tune filament turnover rates, which can vary widely for different actin structures. PMID- 26996944 TI - Determinants of sport-specific postural control strategy and balance performance of amateur rugby players. AB - OBJECTIVES: Postural control strategy and balance performance of rugby players are important yet under-examined issues. This study aimed to examine the differences in balance strategy and balance performance between amateur rugby players and non-players, and to explore training- and injury-related factors that may affect rugby players' balance outcomes. DESIGN: Cross-sectional and exploratory study. METHODS: Forty-five amateur rugby players and 41 healthy active individuals participated in the study. Balance performance and balance strategies were assessed using the sensory organization test (SOT) of the Smart Equitest computerized dynamic posturography machine. Rugby training history and injury history were solicited from the participants. RESULTS: The SOT strategy scores were 1.99-54.90% lower in the rugby group than in the control group (p<0.05), and the equilibrium scores were 1.06-14.29% lower in the rugby group than in the control group (p<0.05). After accounting for age, sex and body mass index, only length of rugby training (in years) was independently associated with the SOT condition 6 strategy score, explaining 15.7% of its variance (p=0.006). There was no association between SOT condition 6 strategy/equilibrium scores and injury history among the rugby players (p>0.05). CONCLUSIONS: Amateur rugby players demonstrated inferior balance strategy and balance performance compared to their non-training counterparts. Their suboptimal balance strategy was associated with insufficient training experience but not with history of injury. PMID- 26996945 TI - Sonographic evaluation of the effect of long-term exercise on Achilles tendon stiffness using shear wave elastography. AB - OBJECTIVES: This study aimed to assess the feasibility of using quantitative shear wave elastography (SWE) to assess the stiffness (Young's modulus) of Achilles tendon and to investigate the effect of long-term weight-bearing exercise on the stiffness of human Achilles tendon by comparing the frequent and infrequent exercise groups. DESIGN: Case-control study. METHODS: A total of 36 healthy subjects aged 19-25 were recruited. Subjects were categorized into frequent and infrequent exercise groups dependent on their level of lower limb weight bearing exercise. B-mode and shear-wave ultrasound examination of Achilles tendon were performed. Measurements of the Achilles tendon stiffness were conducted with the foot position standardized by an ankle fixer. To evaluate inter and intra-operator reliability of Young's modulus measurements, each subject was scanned by three operators and each operator scanned the subject three times. RESULTS: The intra-operator reliability of Young's modulus measurements ranged between 0.803 and 0.845. The inter-operator measurement reliability was 0.585. Result showed that Achilles tendon on non-dominant ankle in frequent-exercisers (median: 320.1kPa) was significantly stiffer than that in infrequent-exercisers (median: 296kPa) (p<0.05), whereas there was no significant difference in Achilles tendon stiffness on dominant ankle between the two groups (p>0.05). CONCLUSIONS: Shear wave elastography is feasible for assessing the Achilles tendon's stiffness in vivo. The stiffness of Achilles tendon of frequent exercisers was significantly higher than that of infrequent-exercisers on non dominant ankle but not on dominant ankle. With the use of an ankle fixer, there was high repeatability and moderate reproducibility in SWE measurement of Achilles tendon stiffness. PMID- 26996946 TI - Musculoskeletal screening as a predictor of seasonal injury in elite Olympic class sailors. AB - OBJECTIVES: To investigate seasonal injury incidence and musculoskeletal screening as a predictor of injury in elite Olympic class sailors. DESIGN: Prospective cohort study. METHODS: A 12-month analysis of injury surveillance data was performed for elite Australian sailors (age=16-30 years, N=22). Pre season musculoskeletal screening (incorporating mobility, stability and neural tests) and seasonal injury data were analysed for predictive relationships, and associations between potential predictor variables and injury status. RESULTS: Injuries requiring medical attention occurred at a rate of 3.6 injuries/athlete, while injuries resulting in disability occurred at a rate of 0.6 injuries/athlete, with the lumbar spine the main site of injury (23% and 33%, respectively). Wrist and hand injury resulted in the highest number of days of disability (110 days), followed by injury to the lumbar spine (87 days). Across the season 75% of injuries to the lumbar spine occurred in the latter half of the season. The only screening measure predictive of injured/uninjured status was better left-sided single-leg decline-squat performance (OR=0.29; 95% CI=0.09 0.88; p=0.03), while increasing age was significantly (p=0.03) associated with thoracic (OR=1.48; 95% CI=1.03-2.12) and lumbar spine (OR=1.46; 95% CI=1.04-2.04) injury. CONCLUSIONS: Though clinically useful, current screening protocols do not adequately assess the risk of seasonal injury in elite Olympic class sailors, and should be revised. Due to the increased risk of spinal injury and potential lost/modified participation in older Olympic class sailors, injury prevention activities should be individualised and age appropriate. PMID- 26996947 TI - Patterns of time use among regional and rural adolescent girls: Associations with correlates of physical activity and health-related quality of life. AB - OBJECTIVES: To describe patterns of time use among regional and rural adolescent girls and compare identified clusters with respect to correlates of physical activity (PA) and health-related quality of life (HRQoL). DESIGN: Cross-sectional PA and lifestyle survey. METHODS: Data were from Year 7-9 adolescent girls (aged 12-15 years) from 16 schools involved in a cluster-randomised trial in regional and rural Victoria, Australia (n=494). Time use data were collected using 24-h Previous Day Physical Activity Recall (PDPAR-24) questionnaire, collapsed into 17 categories of time use. Differences between time use clusters with regard to demographics, correlates of PA and HRQoL measured using PedsQL 4.0 Generic Core Scales, were investigated. RESULTS: Two time use clusters were identified and were associated with correlates of PA and HRQoL. Girls who spent significantly more time in teams sports, non-team sports, school classes, watching TV and sleeping had higher levels of positively aligned PA correlates (e.g. self efficacy, perceived sports competence) and HRQoL than girls characterised with high levels of computer use and video gaming. CONCLUSIONS: These findings highlight how different activity patterns of regional and rural girls affect HRQoL and can inform future intervention strategies to improve PA levels and HRQoL. Clusters characterised by low levels of PA and high computer use and video gaming require targeted interventions to address barriers to their participation. PMID- 26996950 TI - Designing molecular structure to achieve ductile fracture behavior in a stiff and strong 2D polymer, "graphylene". AB - As the simplest two-dimensional (2D) polymer, graphene has immensely high intrinsic strength and elastic stiffness but has limited toughness due to brittle fracture. We use atomistic simulations to explore a new class of graphene/polyethylene hybrid 2D polymer, "graphylene", that exhibits ductile fracture mechanisms and has a higher fracture toughness and flaw tolerance than graphene. A specific configuration of this 2D polymer hybrid, denoted "GrE-2" for the two-carbon-long ethylene chains connecting benzene rings in the inherent framework, is prioritized for study. MD simulations of crack propagation show that the energy release rate to propagate a crack in GrE-2 is twice that of graphene. We also demonstrate that GrE-2 exhibits delocalized failure and other energy-dissipating fracture mechanisms such as crack branching and bridging. These results demonstrate that 2D polymers can be uniquely tailored to achieve a balance of fracture toughness with mechanical stiffness and strength. PMID- 26996948 TI - Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia. AB - Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 various proteins to the cell surface. At least 27 genes are involved in biosynthesis and transport of GPI-anchored proteins (GPI-APs). To date, mutations in 13 of these genes are known to cause inherited GPI deficiencies (IGDs), and all are inherited as recessive traits. IGDs mainly manifest as intellectual disability, epilepsy, coarse facial features, and multiple organ anomalies. These symptoms are caused by the decreased surface expression of GPI-APs or by structural abnormalities of GPI. Here, we present five affected individuals (from two consanguineous families from Egypt and Pakistan and one non-consanguineous family from Japan) who show intellectual disability, hypotonia, and early-onset seizures. We identified pathogenic variants in PIGG, a gene in the GPI pathway. In the consanguineous families, homozygous variants c.928C>T (p.Gln310(*)) and c.2261+1G>C were found, whereas the Japanese individual was compound heterozygous for c.2005C>T (p.Arg669Cys) and a 2.4 Mb deletion involving PIGG. PIGG is the enzyme that modifies the second mannose with ethanolamine phosphate, which is removed soon after GPI is attached to the protein. Physiological significance of this transient modification has been unclear. Using B lymphoblasts from affected individuals of the Egyptian and Japanese families, we revealed that PIGG activity was almost completely abolished; however, the GPI-APs had normal surface levels and normal structure, indicating that the pathogenesis of PIGG deficiency is not yet fully understood. The discovery of pathogenic variants in PIGG expands the spectrum of IGDs and further enhances our understanding of this etiopathogenic class of intellectual disability. PMID- 26996951 TI - Accurate prediction of black rot epidemics in vineyards using a weather-driven disease model. AB - BACKGROUND: Grapevine black rot caused by Guignardia bidwellii is a serious threat in vineyards, especially in areas with cool and humid springs. A mechanistic, weather-driven model was recently developed for the detailed prediction of black rot epidemics. The aim of this work was to evaluate the model by comparison with observed disease development in leaves and clusters in a vineyard in north Italy from 2013 to 2015. RESULTS: The model accurately predicted disease onset. The probability of predicting new infections that did not occur (i.e. unjustified alarms) was <=0.180, while the probability of missing actual infections was 0.175 for leaves and 0.263 for clusters. In 78% of these false negative predictions, the difference between expected and actual disease onset was +/-2 days; therefore, only one infection period was actually missed by the model. The model slightly overestimated disease severity (mainly on leaves) when the observed disease severity was >0.6. CONCLUSION: The model was highly accurate and robust in predicting the infection periods and dynamics of black rot epidemics. The model can be used for scheduling fungicide sprays in vineyards. (c) 2016 Society of Chemical Industry. PMID- 26996949 TI - GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy. AB - The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.Ala150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIEbeta). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIEalpha and TFIIEbeta) as well as decreased phosphorylation of TFIIEalpha in cells from both children. Interestingly, decreased phosphorylation of TFIIEalpha was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP. PMID- 26996952 TI - Moisture effects on the electrochemical reaction and resistance switching at Ag/molybdenum oxide interfaces. AB - An important potential application of solid state electrochemical reactions is in redox-based resistive switching memory devices. Based on the fundamental switching mechanisms, the memory has been classified into two modes, electrochemical metallization memory (ECM) and valence change memory (VCM). In this work, we have investigated a solid state electrochemical cell with a simple Ag/MoO3-x/fluorine-doped tin oxide (FTO) sandwich structure, which shows a normal ECM switching mode after an electroforming process. While in the lower voltage sweep range, the switching behavior changes to VCM-like mode with the opposite switching polarity to the ECM mode. By current-voltage measurements under different ambient atmospheres and X-ray photoemission spectroscopy analysis, electrochemical anodic passivation of the Ag electrode and valence change of molybdenum ions during resistance switching have been demonstrated. The crucial role of moisture adsorption in the switching mode transition has been clarified based on the Pourbaix diagram for the Ag-H2O system for the first time. These results provide a fundamental insight into the resistance switching mechanism model in solid state electrochemical cells. PMID- 26996953 TI - Mean squared displacement from fluorescence correlation spectroscopy. AB - Under certain conditions, the mean squared displacement (MSD) can be retrieved from fluorescence correlation spectroscopy (FCS) measurements. However, in the general case this procedure is not valid, and the apparent MSD obtained from FCS data may substantially differ from the true one. In this work we discuss under which conditions this procedure can be applied. Furthermore, we use computer simulations to obtain the MSD and the apparent MSD for the diffusion of a single polymer chain under various approximations. Based on the simulation results we discuss the reliability of the apparent MSD obtained from FCS, showing that it systematically deviates from the true MSD. We also propose a general procedure to verify the reliability of the apparent MSD by measurements at various focal spot sizes. PMID- 26996955 TI - Spa therapy and knee osteoarthritis: A systematic review. AB - BACKGROUND: Osteoarthritis (OA) is a public health problem that will probably increase in the future with the aging of the population. Crenobalneotherapy is commonly used to treat OA, but evidence from previous reviews was not sufficient. This systematic review aimed to identify the best evidence for the clinical effect of crenobalneotherapy for knee OA. METHODS: We systematically searched MEDLINE via PubMed, PEDRO and the Cochrane Central Register of Controlled Trials for articles published up to September 2015. Articles were included if trials were comparative, if one or more of the subgroups had knee OA with separate data, and if spa therapy or any hydrotherapy techniques involving mineral water or mineral mud was compared to any other intervention or no treatment. Statistical validity, external validity and quality of side effects assessment were evaluated by personal checklists. Risk of bias was assessed by the CLEAR NTP. RESULTS: Treatments (hot mineral water baths, mud therapy, hot showers, and sometimes massage and supervised water exercises) delivered in spa centers across Europe and the Middle East seem to improve symptoms in knee OA. They may be effective for pain and function. There are conflicting results about the effect on quality of life and drug consumption. CONCLUSIONS: Improvements with spa therapy for knee OA appear to be clinically relevant until 3 to 6 months and sometimes 9 months. PMID- 26996954 TI - Effect of Alzheimer's Disease Risk Variant rs3824968 at SORL1 on Regional Gray Matter Volume and Age-Related Interaction in Adult Lifespan. AB - Sortilin receptor 1 (SORL1) is involved in cellular trafficking of amyloid precursor protein and plays an essential role in amyloid-beta peptide generation in Alzheimer disease (AD). The major A allele in a SORL1 single nucleotide polymorphism (SNP), rs3824968, is associated with an increased AD risk. However, the role of SORL1 rs3824968 in the normal ageing process has rarely been examined in relation to brain structural morphology. This study investigated the association between SORL1 rs3824968 and grey matter (GM) volume in a nondemented Chinese population of 318 adults within a wide age range (21-92 years). Through voxel-based morphometry, we found that participants carrying SORL1 allele A exhibited significantly smaller GM volumes in the right posterior cingulate, left middle occipital, medial frontal, and superior temporal gyri. Considerable interaction between age and SORL1 suggested a detrimental and accelerated ageing effect of allele A on putamen. These findings provide evidence that SORL1 rs3824968 modulates regional GM volume and is associated with brain trajectory during the adult lifespan. PMID- 26996956 TI - Assessment tools for personalizing training intensity during cardiac rehabilitation: Literature review and practical proposals. AB - Exercise training, associated with therapeutic education, is the main axis of cardiac rehabilitation (CR) programs. The aim of this study was to review the literature for descriptions of the various assessments of exercise tolerance used to prescribe exercise intensity during CR. A secondary objective was to attempt to formulate a rational practice with these assessments in CR programs. PMID- 26996957 TI - Association of miR-34a-3p/5p, miR-141-3p/5p, and miR-24 in Decidual Natural Killer Cells with Unexplained Recurrent Spontaneous Abortion. AB - BACKGROUND: The specific causes of recurrent spontaneous abortion (RSA) remain unknown in 37-79% of affected women. The aim of this study was to explore the expression levels of 6 miRNAs in natural killer (NK) cells from the decidua of patients with unexplained RSA (URSA) and to predict the target genes of 3 miRNAs. MATERIAL/METHODS: Two groups were examined: URSA (n=20) and controls (n=20). Flow cytometry analysis was used to identify NK cells isolated from the decidua. Transcriptional levels of miRNA were monitored using quantitative real-time reverse transcription-polymerase chain reaction. Prediction and analysis of mRNA targets of differentially expressed miRNAs were performed using bioinformatics methods. RESULTS: Five miRNAs [miR-34a (+281%, P<0.001), miR-155 (+396%, P<0.001), miR-141 (+142%, P<0.01), miR-125a (+279%, P<0.001), and miR-125b (+185%, P<0.001)] were up-regulated, while miR-24 was down-regulated (-64%, P<0.01) in the URSA group, compared to the control group. This study identified potential miRNA targets: miR-34a-3p/5p, 585/1718 (targets of miR-34a-3p/targets of miR-34a-5p), miR-141-3p/5p, 2270/629 (targets of miR-141-3p/targets of miR-141 5p), and miR-24, 2320 target genes. A total of 140 pathways related to target genes were identified including PI3K-Akt, focal adhesion, MAPK, Wnt, regulation of the actin cytoskeleton, T cell receptor, TGF-beta, and estrogen signaling pathways. CONCLUSIONS: This study suggests that miR-34a-3p/5p, miR-141-3p/5p, and miR-24 in decidual NK cells could be associated with URSA. These findings might contribute to the panel of diagnostic and prognostic biomarkers with clinical utility, and facilitate the development of new strategies for targeted therapy against URSA. PMID- 26996958 TI - Determination of anti-tuberculosis drug concentration and distribution from sustained release microspheres in the vertebrae of a spinal tuberculosis rabbit model. AB - There have been several sustained-release materials containing anti-tuberculosis drug to enhance concentration in foci of spinal tuberculosis but what map by which composite drug delivery system is released is not known. Isoniazid (INH) lactic-co-glycolic acid (PLGA) and INH hydroxyapatite (HA) microspheres were prepared, respectively. The rabbits were modeled by tuberculosis strains and sustained-release microspheres were incubated in the foci. INH concentrations in the HA group were higher than those of INH and PLGA groups at L3, L4, and L5 vertebra 2 days after the drugs were embedded (p < 0.05). INH concentrations in the HA group were higher than those of INH and PLGA groups in L3 vertebra 4 days after the drugs were embedded (p < 0.05). INH concentrations in the PLGA group were higher than those of INH and HA groups in L5 vertebra; INH concentrations of the HA group were higher than those of INH and PLGA groups in L4 vertebra 6 days after the drugs were embedded (p < 0.05). These microspheres can enhance INH concentration in the foci. Furthermore, HA microspheres elicit osteogenic effects. HA is better than PLGA in terms of infiltration, but PLGA is better than HA in terms of distribution. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:200-208, 2017. PMID- 26996960 TI - Ring Separation Highlights the Protein-Folding Mechanism Used by the Phage EL Encoded Chaperonin. AB - Chaperonins are ubiquitous, ATP-dependent protein-folding molecular machines that are essential for all forms of life. Bacteriophage phiEL encodes its own chaperonin to presumably fold exceedingly large viral proteins via profoundly different nucleotide-binding conformations. Our structural investigations indicate that ATP likely binds to both rings simultaneously and that a misfolded substrate acts as the trigger for ATP hydrolysis. More importantly, the phiEL complex dissociates into two single rings resulting from an evolutionarily altered residue in the highly conserved ATP-binding pocket. Conformational changes also more than double the volume of the single-ring internal chamber such that larger viral proteins are accommodated. This is illustrated by the fact that phiEL is capable of folding beta-galactosidase, a 116-kDa protein. Collectively, the architecture and protein-folding mechanism of the phiEL chaperonin are significantly different from those observed in group I and II chaperonins. PMID- 26996961 TI - Non-Linear and Flexible Regions of the Human Notch1 Extracellular Domain Revealed by High-Resolution Structural Studies. AB - The Notch receptor is a key component of a core metazoan signaling pathway activated by Delta/Serrate/Lag-2 ligands expressed on an adjacent cell. This results in a short-range signal with profound effects on cell-fate determination, cell proliferation, and cell death. Key to understanding receptor function is structural knowledge of the large extracellular portion of Notch which contains multiple repeats of epidermal growth factor (EGF)-like domains. Here we investigate the EGF4-13 region of human Notch1 (hN1) using a multidisciplinary approach. Ca(2+)-binding measurements, X-ray crystallography, {(1)H}-(15)N heteronuclear nuclear Overhauser effects, and residual dipolar couplings support a non-linear organization for the EGF4-13 region with a rigid, bent conformation for EGF4-7 and a single flexible linkage between EGF9 and EGF10. These data allow us to construct an informed model for EGF10-13 which, in conjunction with comparative binding studies, demonstrates that EGF10 has an important role in determining Notch receptor sensitivity to Dll-4. PMID- 26996962 TI - A Non-Stem-Loop CRISPR RNA Is Processed by Dual Binding Cas6. AB - A subclass of recently discovered CRISPR repeat RNA in bacteria contains minimally recognizable structural features that facilitate an unknown mechanism of recognition and processing by the Cas6 family of endoribonucleases. Cocrystal structures of Cas6 from Methanococcus maripaludis (MmCas6b) bound with its repeat RNA revealed a dual site binding structure and a cleavage site conformation poised for phosphodiester bond breakage. Two non-interacting MmCas6b bind to two separate AAYAA motifs within the same repeat, one distal and one adjacent to the cleavage site. This bound structure potentially competes with a stable but non productive RNA structure. At the cleavage site, MmCas6b supplies a base pair mimic to stabilize a short 2 base pair stem immediately upstream of the scissile phosphate. Complementary biochemical analyses support the dual-AAYAA binding model and a critical role of the protein-RNA base pair mimic. Our results reveal a previously unknown method of processing non-stem-loop CRISPR RNA by Cas6. PMID- 26996959 TI - Acoustic Injectors for Drop-On-Demand Serial Femtosecond Crystallography. AB - X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallization conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. We report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). Additional samples were screened to demonstrate that these methods can be applied to rare samples. PMID- 26996963 TI - New Structural Insights into the Genome and Minor Capsid Proteins of BK Polyomavirus using Cryo-Electron Microscopy. AB - BK polyomavirus is the causative agent of several diseases in transplant patients and the immunosuppressed. In order to better understand the structure and life cycle of BK, we produced infectious virions and VP1-only virus-like particles in cell culture, and determined their three-dimensional structures using cryo electron microscopy (EM) and single-particle image processing. The resulting 7.6 A resolution structure of BK and 9.1-A resolution of the virus-like particles are the highest-resolution cryo-EM structures of any polyomavirus. These structures confirm that the architecture of the major structural protein components of these human polyomaviruses are similar to previous structures from other hosts, but give new insight into the location and role of the enigmatic minor structural proteins, VP2 and VP3. We also observe two shells of electron density, which we attribute to a structurally ordered part of the viral genome, and discrete contacts between this density and both VP1 and the minor capsid proteins. PMID- 26996965 TI - 'From past to future' - deciphering the molecular basis of Alzheimer's disease through the pages of the Journal of Neurochemistry. AB - The Journal of Neurochemistry has made significant contributions to unraveling the molecular basis for Alzheimer's disease during its 60-year history. To mark its 60th anniversary, this review describes the association between the journal and Alzheimer's disease research - from the early years when Alzheimer's disease was a minor topic in the journal through to the molecular era in the mid-1980s. This coincided with a number of the highly cited Alzheimer's disease studies which described fundamental aspects of the neurochemistry of Alzheimer's disease and encompassed the themes of oxidative stress and post-translational modifications, cholinergic system, tau, purification of Abeta, defining the Abeta toxic species, mechanism of amyloid precursor protein processing, and the development of diagnostics and therapeutics. The Journal of Neurochemistry has made significant contributions toward unraveling the molecular, cellular and pathological basis of Alzheimer's disease through its 60 years. This article is part of the 60th Anniversary special issue. PMID- 26996964 TI - Computationally Designed Bispecific Antibodies using Negative State Repertoires. AB - A challenge in the structure-based design of specificity is modeling the negative states, i.e., the complexes that you do not want to form. This is a difficult problem because mutations predicted to destabilize the negative state might be accommodated by small conformational rearrangements. To overcome this challenge, we employ an iterative strategy that cycles between sequence design and protein docking in order to build up an ensemble of alternative negative state conformations for use in specificity prediction. We have applied our technique to the design of heterodimeric CH3 interfaces in the Fc region of antibodies. Combining computationally and rationally designed mutations produced unique designs with heterodimer purities greater than 90%. Asymmetric Fc crystallization was able to resolve the interface mutations; the heterodimer structures confirmed that the interfaces formed as designed. With these CH3 mutations, and those made at the heavy-/light-chain interface, we demonstrate one-step synthesis of four fully IgG-bispecific antibodies. PMID- 26996966 TI - Antimicrobial properties of two novel peptides derived from Theobroma cacao osmotin. AB - The osmotin proteins of several plants display antifungal activity, which can play an important role in plant defense against diseases. Thus, this protein can be useful as a source for biotechnological strategies aiming to combat fungal diseases. In this work, we analyzed the antifungal activity of a cacao osmotin like protein (TcOsm1) and of two osmotin-derived synthetic peptides with antimicrobial features, differing by five amino acids residues at the N-terminus. Antimicrobial tests showed that TcOsm1 expressed in Escherichia coli inhibits the growth of Moniliophthora perniciosa mycelium and Pichia pastoris X-33 in vitro. The TcOsm1-derived peptides, named Osm-pepA (H-RRLDRGGVWNLNVNPGTTGARVWARTK-NH2), located at R23-K49, and Osm-pepB (H-GGVWNLNVNPGTTGARVWARTK-NH2), located at G28 K49, inhibited growth of yeasts (Saccharomyces cerevisiae S288C and Pichia pastoris X-33) and spore germination of the phytopathogenic fungi Fusarium f. sp. glycines and Colletotrichum gossypi. Osm-pepA was more efficient than Osm-pepB for S. cerevisiae (MIC=40MUM and MIC=127MUM, respectively), as well as for P. pastoris (MIC=20MUM and MIC=127MUM, respectively). Furthermore, the peptides presented a biphasic performance, promoting S. cerevisiae growth in doses around 5MUM and inhibiting it at higher doses. The structural model for these peptides showed that the five amino acids residues, RRLDR at Osm-pepA N-terminus, significantly affect the tertiary structure, indicating that this structure is important for the peptide antimicrobial potency. This is the first report of development of antimicrobial peptides from T. cacao. Taken together, the results indicate that the cacao osmotin and its derived peptides, herein studied, are good candidates for developing biotechnological tools aiming to control phytopathogenic fungi. PMID- 26996967 TI - Time course of hepatic gene expression and plasma vitellogenin protein concentrations in estrone-exposed juvenile rainbow trout (Oncorhynchus mykiss). AB - Estrone (E1), a natural estrogen hormone found in sewage effluents and surface waters, has known endocrine disrupting effects in fish, thus, it is a contaminant of emerging concern. Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to an environmentally-relevant concentration of E1 (24ng/L E1 [0.1nM]) for 7d and then placed in clean water for a 9d recovery period. RNA sequencing showed transcripts from numerous affected biological processes (e.g. immune, metabolic, apoptosis, clotting, and endocrine) were altered by E1 after 4d of treatment. The time course of E1-inducible responses relating to vitellogenesis was examined daily during the two phases of exposure. Hepatic gene expression alterations evaluated by quantitative polymerase chain reaction (QPCR) were found during the treatment period for vitellogenin (VTG), vitelline envelope proteins (VEPs) alpha, beta and gamma, and estrogen receptor alpha1 (ERalpha1) transcripts. ERalpha1 was the only transcript induced each day during the treatment phase, thus it was a good indicator of E1 exposure. Gradual increases occurred in VEPbeta and VEPgamma transcripts, peaking at d7. VTG transcript was only elevated at d4, making it less sensitive than VEPs to this low-level E1 treatment. Inductions of ERalpha1, VEPalpha, VEPbeta and VEPgamma transcripts ceased 1d into the recovery phase. Plasma VTG protein concentrations were not immediately elevated but peaked 7d into the recovery phase. Thus, elevated vitellogenesis related gene expression and protein production occurred slowly but steadily at this concentration of E1, confirming the sequence of events for transcripts and VTG protein responses to xenoestrogen exposure. PMID- 26996969 TI - Diagnostic criteria for congenital biliary dilatation 2015. AB - BACKGROUND: The Diagnostic Criteria for Pancreaticobiliary Maljunction 2013 were published by the Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) in 2014. The committee of JSGPM for diagnostic criteria for pancreaticobiliary maljunction has established the standard diameter of the bile duct, and a definition of dilatation of the bile duct was proposed in 2014. METHODS: The committee of JSGPM prepared the diagnostic criteria for congenital biliary dilatation in 2014, and a final revised version was approved in 2015. RESULTS: Congenital biliary dilatation is defined as a congenital malformation involving both local dilatation of the extrahepatic bile duct, including the common bile duct, and pancreaticobiliary maljunction. However, cases associated with intrahepatic bile duct dilatation can also be included. Various kinds of pathological conditions can occur on hepatobiliary systems and pancreas by bile duct dilatation and pancreaticobiliary maljunction. For a diagnosis of congenital biliary dilatation, both abnormal dilatation of the bile duct and pancreaticobiliary maljunction must be evident by either imaging test or anatomical examination. Acquired or secondary dilatation of the bile duct by obstruction due to biliary stones or malignancy should be strictly excluded. CONCLUSION: Diagnostic criteria for congenital biliary dilatation 2015 were established from Japan representing a world first. PMID- 26996970 TI - Analytical gradients for excitation energies from frozen-density embedding. AB - The formulation of analytical excitation-energy gradients from time-dependent density functional theory within the frozen-density embedding framework is presented. In addition to a comprehensive mathematical derivation, we discuss details of the numerical implementation in the Slater-function based Amsterdam Density Functional (ADF) program. Particular emphasis is put on the consistency in the use of approximations for the evaluation of second- and third-order non additive kinetic-energy and exchange-correlation functional derivatives appearing in the final expression for the excitation-energy gradient. We test the implementation for different chemical systems in which molecular excited-state potential-energy curves are affected by another subsystem. It is demonstrated that the analytical implementation for the evaluation of excitation-energy gradients yields results in close agreement with data from numerical differentiation. In addition, we show that our analytical results are numerically more stable and thus preferable over the numerical ones. PMID- 26996968 TI - HIV-1 cellular and tissue replication patterns in infected humanized mice. AB - Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study HIV-1 biology, virology, immunology, pathogenesis and therapeutic development has served as a robust alternative to more-well developed animal models for HIV/AIDS. A critical component in reflecting such human pathobiology rests in defining the tissue and cellular sites for HIV-1 infection. To this end, we examined the tissue sites for viral infection in bone marrow, blood, spleens, liver, gut, brain, kidney and lungs of human CD34+ hematopoietic stem cell engrafted virus-infected NOD.Cg Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Cells were analyzed by flow cytometry and sorted from species mixtures defined as CD34+ lineage negative progenitor cells, CD14+CD16+ monocyte-macrophages and central, stem cell and effector memory T cells. The cell distribution and viral life cycle were found dependent on the tissue compartment and time of infection. Cell subsets contained HIV-1 total and integrated DNA as well as multi-spliced and unspliced RNA in divergent proportions. The data support the idea that humanized mice can provide a means to examine the multifaceted sites of HIV-1 replication including, but not limited to progenitor cells and monocyte-macrophages previously possible only in macaques and human. PMID- 26996972 TI - Comparison of CT and MRI findings for cervical spine clearance in obtunded patients without high impact trauma. PMID- 26996971 TI - Functional C-TERMINALLY ENCODED PEPTIDE (CEP) plant hormone domains evolved de novo in the plant parasite Rotylenchulus reniformis. AB - Sedentary plant-parasitic nematodes (PPNs) induce and maintain an intimate relationship with their host, stimulating cells adjacent to root vascular tissue to re-differentiate into unique and metabolically active 'feeding sites'. The interaction between PPNs and their host is mediated by nematode effectors. We describe the discovery of a large and diverse family of effector genes, encoding C-TERMINALLY ENCODED PEPTIDE (CEP) plant hormone mimics (RrCEPs), in the syncytia forming plant parasite Rotylenchulus reniformis. The particular attributes of RrCEPs distinguish them from all other CEPs, regardless of origin. Together with the distant phylogenetic relationship of R. reniformis to the only other CEP encoding nematode genus identified to date (Meloidogyne), this suggests that CEPs probably evolved de novo in R. reniformis. We have characterized the first member of this large gene family (RrCEP1), demonstrating its significant up-regulation during the plant-nematode interaction and expression in the effector-producing pharyngeal gland cell. All internal CEP domains of multi-domain RrCEPs are followed by di-basic residues, suggesting a mechanism for cleavage. A synthetic peptide corresponding to RrCEP1 domain 1 is biologically active and capable of up regulating plant nitrate transporter (AtNRT2.1) expression, whilst simultaneously reducing primary root elongation. When a non-CEP-containing, syncytia-forming PPN species (Heterodera schachtii) infects Arabidopsis in a CEP-rich environment, a smaller feeding site is produced. We hypothesize that CEPs of R. reniformis represent a two-fold adaptation to sustained biotrophy in this species: (i) increasing host nitrate uptake, whilst (ii) limiting the size of the syncytial feeding site produced. PMID- 26996973 TI - [Bone in skin]. PMID- 26996974 TI - [Not Available]. PMID- 26996976 TI - [Editorial]. PMID- 26996978 TI - Learning from 7 Years of Experience with Sorafenib in Advanced HCC: Sorafenib Better than Sorafenib? PMID- 26996977 TI - Clinics in diagnostic imaging (166). Nonketotic hyperglycaemic chorea hemiballismus. AB - A 68-year-old woman with poorly controlled diabetes mellitus presented to the emergency department with choreoathetoid movements affecting the upper and lower left limbs. Computed tomography of the brain did not show any intracranial abnormalities. However, subsequent magnetic resonance (MR) imaging of the brain revealed an increased T1 signal in the right basal ganglia, raising the suspicion of nonketotic hyperglycaemic chorea-hemiballismus. Management consisted of adjusting her insulin dose to achieve good glycaemic control. The patient subsequently recovered and was discharged after eight days. There are many causes of basal ganglia T1 hyperintensity, including hyperglycaemia in patients with poorly controlled diabetes mellitus. This case emphasises the importance of MR imaging in the early diagnosis of hyperglycaemia as a cause of chorea hemiballismus, to enable early treatment and a better clinical outcome. PMID- 26996975 TI - Long non-coding RNA regulation of gene expression during differentiation. AB - Transcriptome analysis of mammalian genomes has revealed widespread transcription, much of which does not encode protein. Long non-coding RNAs (lncRNAs) are a subset of the non-coding transcriptome that are emerging as critical regulators of various cellular processes. Differentiation of stem and progenitor cells requires a careful execution of specific genetic programs, and recent studies have revealed that lncRNA expression contributes to specification of cell identity. LncRNAs participate in regulating differentiation at multiple levels of gene expression through various mechanisms of action. In this review, functional roles of lncRNAs in regulating cellular differentiation of blood, muscle, skin, cardiomyocytes, adipocytes, and neurons are discussed. PMID- 26996979 TI - Ungulate malaria parasites. AB - Haemosporida parasites of even-toed ungulates are diverse and globally distributed, but since their discovery in 1913 their characterization has relied exclusively on microscopy-based descriptions. In order to bring molecular approaches to bear on the identity and evolutionary relationships of ungulate malaria parasites, we conducted Plasmodium cytb-specific nested PCR surveys using blood from water buffalo in Vietnam and Thailand, and goats in Zambia. We found that Plasmodium is readily detectable from water buffalo in these countries, indicating that buffalo Plasmodium is distributed in a wider region than India, which is the only area in which buffalo Plasmodium has been reported. Two types (I and II) of Plasmodium sequences were identified from water buffalo and a third type (III) was isolated from goat. Morphology of the parasite was confirmed in Giemsa-reagent stained blood smears for the Type I sample. Complete mitochondrial DNA sequences were isolated and used to infer a phylogeny in which ungulate malaria parasites form a monophyletic clade within the Haemosporida, and branch prior to the clade containing bird, lizard and other mammalian Plasmodium. Thus it is likely that host switching of Plasmodium from birds to mammals occurred multiple times, with a switch to ungulates independently from other mammalian Plasmodium. PMID- 26996981 TI - Sepsis 2016 Agra, India. Agra, India. 5-6 February 2016. PMID- 26996980 TI - Sweet potato NAC transcription factor, IbNAC1, upregulates sporamin gene expression by binding the SWRE motif against mechanical wounding and herbivore attack. AB - Sporamin is a tuberous storage protein with trypsin inhibitory activity in sweet potato (Ipomoea batatas Lam.), which accounts for 85% of the soluble protein in tubers. It is constitutively expressed in tuberous roots but is expressed in leaves only after wounding. Thus far, its wound-inducible signal transduction mechanisms remain unclear. In the present work, a 53-bp DNA region, sporamin wound-response cis-element (SWRE), was identified in the sporamin promoter and was determined to be responsible for the wounding response. Using yeast one hybrid screening, a NAC domain protein, IbNAC1, that specifically bound to the 5' TACAATATC-3' sequence in SWRE was isolated from a cDNA library from wounded leaves. IbNAC1 was constitutively expressed in root tissues and was induced earlier than sporamin following the wounding of leaves. Transgenic sweet potato plants overexpressing IbNAC1 had greatly increased sporamin expression, increased trypsin inhibitory activity, and elevated resistance against Spodoptera litura. We further demonstrated that IbNAC1 has multiple biological functions in the jasmonic acid (JA) response, including the inhibition of root formation, accumulation of anthocyanin, regulation of aging processes, reduction of abiotic tolerance, and overproduction of reactive oxygen species (ROS). Thus, IbNAC1 is a core transcription factor that reprograms the transcriptional response to wounding via the JA-mediated pathway in sweet potato. PMID- 26996982 TI - Reasons why patients referred to diabetes education programmes choose not to attend: a systematic review. AB - AIMS: To identify the reasons why those offered a place on diabetes education programmes declined the opportunity. BACKGROUND: It is well established that diabetes education is critical to optimum diabetes care; it improves metabolic control, prevents complications, improves quality of life and empowers people to make informed choices to manage their condition. Despite the significant clinical and personal rewards offered by diabetes education, programmes are underused, with a significant proportion of patients choosing not to attend. METHODS: A systematic search of the following databases was conducted for the period from 2005-2015: Medline; EMBASE; Scopus; CINAHL; and PsycINFO. Studies that met the inclusion criteria focusing on patient-reported reasons for non-attendance at structured diabetes education were selected. RESULTS: A total of 12 studies spanning quantitative and qualitative methodologies were included. The selected studies were published in Europe, USA, Pakistan, Canada and India, with a total sample size of 2260 people. Two broad categories of non-attender were identified: 1) those who could not attend for logistical, medical or financial reasons (e.g. timing, costs or existing comorbidities) and 2) those who would not attend because they perceived no benefit from doing so, felt they had sufficient knowledge already or had emotional and cultural reasons (e.g. no perceived problem, denial or negative feelings towards education). Diabetes education was declined for many reasons, and the range of expressed reasons was more diverse and complex than anticipated. CONCLUSION: New and innovative methods of delivering diabetes education are required which address the needs of people with diabetes whilst maintaining quality and efficiency. PMID- 26996983 TI - HIV/HCV Co-infection: Overcoming Barriers to Treatment. AB - A critical step in the eradication of hepatitis C virus (HCV) infection is access to effective therapy. With the advent of interferon-free regimens, HCV providers and patients gained hope that the success seen in clinical trials could be translated to the real world. However, the exorbitant cost of the new direct acting antivirals limits access to these medications to the general HCV population, especially underserved patients with public insurance. We used a descriptive qualitative approach to detail the measures necessary and challenges faced by an inner-city nursing team in Washington, DC to obtain the new direct acting antivirals. Significant time and dedication on the part of providers and staff was required to assist patients with the process of obtaining direct-acting antivirals. PMID- 26996984 TI - Brief Exposure to Cognitive Behavioral Therapy Reduces Side-Effect Symptoms in Patients on Antiretroviral Therapy. AB - No study has tested the effectiveness of individualized cognitive behavioral therapy (CBT) interventions to reduce persistent nausea, pain, anxiety, and fatigue in patients on continuous antiretroviral therapy (ART). Our objective was to determine if CBT could reduce nausea, pain, anxiety, and fatigue in patients with HIV on ART. Men ages 40 to 56 years on ART (n = 18) at a suburban HIV clinic were randomly assigned to a control group or the CBT intervention. Usual adherence education and side-effect management were provided to both groups. Symptoms, health perception, medication adherence, and side-effect-reducing medication use were measured at four time points over 3 months. Participants in the intervention group rated usual fatigue and worst fatigue at 60 days, and nausea duration at 90 days significantly lower than controls (p < .05). Brief CBT training may reduce fatigue and nausea in patients with HIV undergoing ART. PMID- 26996985 TI - The greater risk of preterm birth in triplets is mirrored by a more rapid cervical shortening along gestation. AB - BACKGROUND: The risk of preterm birth increases with plurality. However, data are limited about the role of cervical length in triplet pregnancies and how the greater predisposition for preterm birth in triplet pregnancies, compared with twin pregnancies, is reflected by cervical length. Specifically, it is unclear whether the greater predisposition of triplet pregnancies for preterm birth is reflected by a more rapid cervical shortening during gestation compared with twin pregnancies (and therefore a shorter cervical length at any given gestational age), by a greater risk for preterm birth per given cervical length at any given gestational age, or both. OBJECTIVE: The purpose of the study was to compare the rate of cervical shortening during gestation and the correlation between cervical length and gestational age at birth in asymptomatic women with triplet vs twin pregnancies. STUDY DESIGN: This was a retrospective study of women with triplet or twin pregnancies who were who were observed in a tertiary center who underwent serial sonographic measurement of cervical length from 16-32 weeks gestation. Change in cervical length during gestation and relationship of cervical length with gestational age at birth were compared between the triplets and twins groups. RESULTS: A total of 431 measurements of cervical length from 86 women with triplets was analyzed and compared with 2826 measurements of cervical length from 441 women with twins. The rate of cervical shortening among triplet pregnancies was higher than among twin pregnancies starting from 18 weeks of gestation (slope of regression line, -1.297 vs -0.907; P < .001). Similarly, the proportion of women with cervical length of <25 mm or 15 mm was higher among triplet pregnancies than among twin pregnancies (34.0% vs 21.0% [P < .001] and 16.7% vs 8.4% [P = .001]), respectively. For any given cervical length measured after 22 weeks of gestation, the associated gestational length at birth in triplet pregnancies was lower by 2.7 weeks on average compared with twin pregnancies (P < .001). CONCLUSION: The higher rate of preterm birth in triplet pregnancies, compared with twin pregnancies, is reflected by both a more rapid cervical shortening during gestation and a lower gestational age at birth per any given cervical length. PMID- 26996986 TI - Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naive women. AB - BACKGROUND: The incidence of opioid-related death in women has increased 5-fold over the past decade. For many women, their initial opioid exposure will occur in the setting of routine medical care. Approximately 1 in 3 deliveries in the United States is by cesarean, and opioids are commonly prescribed for postsurgical pain management. OBJECTIVE: The objective of this study was to determine the risk that opioid-naive women prescribed opioids after cesarean delivery will subsequently become consistent prescription opioid users in the year following delivery and to identify predictors for this behavior. STUDY DESIGN: We identified women in a database of commercial insurance beneficiaries who underwent cesarean delivery and who were opioid naive in the year prior to delivery. To identify persistent users of opioids, we used trajectory models, which group together patients with similar patterns of medication filling during follow-up, based on patterns of opioid dispensing in the year following cesarean delivery. We then constructed a multivariable logistic regression model to identify independent risk factors for membership in the persistent user group. RESULTS: A total of 285 of 80,127 (0.36%, 95% confidence interval, 0.32-0.40), opioid-naive women became persistent opioid users (identified using trajectory models based on monthly patterns of opioid dispensing) following cesarean delivery. Demographics and baseline comorbidity predicted such use with moderate discrimination (c statistic = 0.73). Significant predictors included a history of cocaine abuse (risk, 7.41%; adjusted odds ratio, 6.11, 95% confidence interval, 1.03-36.31) and other illicit substance abuse (2.36%; adjusted odds ratio, 2.78, 95% confidence interval, 1.12-6.91), tobacco use (1.45%; adjusted odds ratio, 3.04, 95% confidence interval, 2.03-4.55), back pain (0.69%; adjusted odds ratio, 1.74, 95% confidence interval, 1.33-2.29), migraines (0.91%; adjusted odds ratio, 2.14, 95% confidence interval, 1.58-2.90), antidepressant use (1.34%; adjusted odds ratio, 3.19, 95% confidence interval, 2.41-4.23), and benzodiazepine use (1.99%; adjusted odds ratio, 3.72, 95% confidence interval, 2.64-5.26) in the year prior to the cesarean delivery. CONCLUSION: A very small proportion of opioid-naive women (approximately 1 in 300) become persistent prescription opioid users following cesarean delivery. Preexisting psychiatric comorbidity, certain pain conditions, and substance use/abuse conditions identifiable at the time of initial opioid prescribing were predictors of persistent use. PMID- 26996987 TI - Detoxification from opiate drugs during pregnancy. AB - BACKGROUND: The current recommendation regarding the management of a pregnant patient with opioid dependence is not to perform detoxification during pregnancy because of a potential risk for preterm labor, fetal distress, or fetal demise. OBJECTIVE: The objective of the study was to evaluate the safety of full opiate detoxification during pregnancy in a large number of patients through 4 different methods and analyze the rate of newborn treatment of neonatal abstinence syndrome for each method. STUDY DESIGN: This was a retrospective analysis of data collected prospectively during ongoing prenatal care of opiate-addicted pregnant women. Data were analyzed for pregnancy complications including fetal demise and preterm labor of opiate-addicted pregnant women who underwent detoxification during pregnancy through 4 different methods: acute detoxification of incarcerated patients; inpatient detoxification with intense outpatient follow-up management; inpatient detoxification without intense outpatient follow-up management; and slow outpatient buprenorphine detoxification. The rates of newborns treated for neonatal abstinence syndrome were also assessed for each group. RESULTS: Over 5.5 years, 301 opiate-addicted pregnant patients were fully detoxified during pregnancy with no adverse fetal outcomes related to detoxification identified. There were 94 patients who delivered newborns treated for neonatal abstinence syndrome (31%). There was an 18.5% rate of neonatal abstinence syndrome in the 108 acutely detoxified while incarcerated, a 17.4% rate of neonatal abstinence syndrome in the 23 who had inpatient detoxification with intense outpatient follow-up management, a 17.2% rate of neonatal abstinence syndrome in the 93 who went through slow outpatient buprenorphine detoxification, but a 70.1% rate of neonatal abstinence syndrome in the 77 who had inpatient detoxification without intense outpatient follow-up management. CONCLUSION: With these data and other published studies, more than 600 patients have been reported to detoxify from opiates during pregnancy with no report of fetal harm related to the process. These data highly suggest that detoxification of opiate-addicted pregnant patients is not harmful. The rate of neonatal abstinence syndrome is high but primarily when no continued long-term follow-up occurs. Once a patient is drug free, intense behavioral health follow-up is needed for continued success. PMID- 26996988 TI - Obesity increases the risk of failure of noninvasive prenatal screening regardless of gestational age. AB - BACKGROUND: Noninvasive prenatal screening has become an increasingly prevalent choice for women who desire aneuploidy screening. Although the test characteristics are impressive, some women are at increased risk for noninvasive prenatal screen failure. The risk of test failure increases with maternal weight; thus, obese women may be at elevated risk for failure. This risk of failure may be mitigated by the addition of a paternal cheek swab and screening at a later gestational age. OBJECTIVE: The purpose of this study was to evaluate the association among obesity, gestational age, and paternal cheek swab in the prevention of screening failure. STUDY DESIGN: A retrospective cohort study was performed for women who were >=35 years old at delivery who underwent screening at NorthShore University HealthSystem, Evanston, IL. Maternal weight, body mass index, gestational age, and a paternal cheek swab were evaluated in univariate and multivariable logistic regression analyses to assess the association with failed screening. RESULTS: Five hundred sixty-five women met inclusion criteria for our study. The mean body mass index was 25.9 +/- 5.1 kg/m(2); 111 women (20%) were obese (body mass index, >=30 kg/m(2)). Forty-four women (7.8%) had a failed screen. Obese women had a failure rate of 24.3% compared with 3.8% in nonobese women (P < .01). Gestational age was not associated with failure rate (mean +/- standard deviation, 13 +/- 3 weeks for both screen failure and nonfailure; P = .76). The addition of a paternal cheek swab reduced the failure rate from 10.2% in women with no swab to 3.8% in women with a swab (P < .01). In multivariable analysis, obesity and lack of a paternal cheek swab were independent predictors of screen failure (odds ratio, 9.75; 95% confidence interval, 4.85-19.61; P < .01; and odds ratio, 3.61; 95% confidence interval, 1.56-8.33; P < .01, respectively). CONCLUSION: The addition of a paternal cheek swab significantly improved noninvasive prenatal screen success rates in obese women. However, delaying testing to a later gestational age did not. PMID- 26996989 TI - Intravenous drug use is associated with alloimmunization in pregnancy. AB - BACKGROUND: Anecdotal evidence has suggested an association of intravenous drug abuse with alloimmunization; however, published data are limited to case reports. OBJECTIVE: The purpose of this study was to determine whether women with a history of intravenous drug abuse have an increased risk of alloimmunization. STUDY DESIGN: A retrospective cohort study was performed with the use of data from a single-center blood bank and perinatal database from 2008-2014. Blood bank data were used to identify women with alloimmunization, which was defined as a positive antibody screen in pregnancy not due to naturally occurring antibodies, agglutinins, autoantibodies, or Rh immunoglobulin administration. Intravenous drug abuse was ascertained from a comprehensive database that has captured all drug abuse in pregnancy since 2008. For women who contributed >1 pregnancy to the database, only the most recent pregnancy was included. The rates of alloimmunization among women with a history of intravenous drug abuse and general obstetric populations were calculated and compared. The distribution of alloantibody types, proportion of Rh-group alloantibodies, and patient Rh status were assessed for intravenous and non-intravenous drug abuse-associated alloimmunization. Characteristics and outcomes between intravenous and non intravenous drug abuse-associated alloimmunization were assessed for women with clinically significant alloantibodies. RESULTS: Alloimmunization was more common in women with a history of intravenous drug abuse (11/305 women; 3.6%) compared to women without a history of intravenous drug abuse (288/16,022 women; 1.8%; relative risk, 2.00; 95% confidence interval, 1.11-3.62). Needle-sharing was present in 7 and suspected in 4 women with an intravenous drug abuse history. Among women with a history of intravenous drug abuse, none had a history of transfusion or traditional risk factor for alloimmunization. The distribution of alloantibodies was different between intravenous drug abuse- and non-intravenous drug abuse-associated alloimmunization. Rh group alloantibodies and Rh-negative status were more common in women with a history of intravenous drug abuse. Among Rh-negative women with a history of intravenous drug abuse, 50% of RhD alloimmunization cases occurred in nulliparous women. The rate of multiple alloantibodies was not different between intravenous drug abuse- and non intravenous drug abuse-associated alloimmunization. CONCLUSION: Maternal history of intravenous drug abuse is associated with an increased risk of alloimmunization. Approximately 1 in 30 intravenous drug abuse women may be diagnosed with an alloantibody in pregnancy. Given the current US opioid epidemic, increased vigilance in screening is required. Needle-sharing represents a possible mechanism for intravenous drug abuse-associated alloimmunization; however, limited obstetric care, failure to obtain Rh immunoglobulin, or failure to identify early pregnancy loss cannot be excluded. PMID- 26996990 TI - Metabolic phenotyping for monitoring ovarian cancer patients. AB - Epithelial ovarian cancer (EOC) is the most deadly of the gynecological cancers. New approaches and better tools for monitoring treatment efficacy and disease progression of EOC are required. In this study, metabolomics using rapid resolution liquid chromatography mass spectrometry was applied to a systematic investigation of metabolic changes in response to advanced EOC, surgery and recurrence. The results revealed considerable metabolic differences between groups. Moreover, 37, 30, and 26 metabolites were identified as potential biomarkers for primary, surgical and recurrent EOC, respectively. Primary EOC was characterized by abnormal lipid metabolism and energy disorders. Oxidative stress and surgical efficacy were clear in the post-operative EOC patients. Recurrent EOC patients showed increased amino acid and lipid metabolism compared with primary EOC patients. After cytoreductive surgery, eight metabolites (e.g. l kynurenine, retinol, hydroxyphenyllactic acid, 2-octenoic acid) corrected towards levels of the control group, and four (e.g. hydroxyphenyllactic acid, 2-octenoic acid) went back again to primary EOC levels after disease relapse. In conclusion, this study delineated metabolic changes in response to advanced EOC, surgery and recurrence, and identified biomarkers that could facilitate both understanding and monitoring of EOC development and progression. PMID- 26996991 TI - The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity. AB - miR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models (pentylenetetrazole- and pilocarpine-induced seizures), while miR-124 inhibitor led to shortened onset latency in pilocarpine-induced seizure rat models. Moreover, the result of local field potentials (LFPs) records further demonstrated miR-124 may have anti-epilepsy function. Inhibition of neuronal firing by miR-124 was associated with the suppression of mEPSC, AMPAR- and NMDAR mediated currents, which were accompanied by decreased surface expression of NMDAR. In addition, miR-124 injection resulted in decreased activity and expression of cAMP-response element-binding protein1 (CREB1). a key regulator in epileptogenesis. A dual-luciferase reporter assay was used to confirm that miR 124 targeted directly the 3'UTR of CREB1 gene and repressed the CREB1 expression in HEK293T cells. Immunoprecipitation studies confirmed that the CREB1 antibody effectively precipitated CREB1 and NMDAR1 but not GLUR1 from rat brain hippocampus. These results revealed a previously unknown function of miR-124 in neuronal excitability and provided a new insight into molecular mechanisms underlying epilepsy. PMID- 26996994 TI - Oxazines: A New Class of Second-Order Nonlinear Optical Switches. AB - A combined experimental-theoretical investigation has revealed that oxazine-based compounds are multiaddressable, multistate, and multifunctional molecular switches exhibiting contrasts of both linear and second-order nonlinear optical properties. The switching properties are particularly large when the substituent is a donor group. In this study, the cleavage of the C-O bond at the junction of the indole and oxazine cycles (of the closed a forms) is acido-triggered, leading to an open form (b(+)) characterized by larger first hyperpolarizabilities (betaHRS) and smaller excitation energies than in the closed form. These results are confirmed and interpreted utilizing ab initio calculations that have been carried out on a broad set of compounds to unravel the role of the substituent. With respect to acceptor groups, oxazines bearing donor groups are characterized not only by larger betaHRS and betaHRS contrast ratios but also by smaller excitation energies, larger opening-induced charge transfer, and reduction of the bond length alternation, as well as smaller Gibbs energies of the opening reaction. Compared to protonated open forms (b(+)), calculations on the zwitterionic open forms (b) have pointed out similarities in the long-wavelength UV/vis absorption spectra, whereas their betaHRS values might differ strongly as a function of the substituent. Indeed, the open forms present two NLOphores, the indoleninium-substituent entity and the nitrophenol (present in the protonated open form, b(+)) or nitrophenolate (present in the zwitterionic open form, b) moiety. Then, nitrophenolate displays a larger first hyperpolarizability than nitrophenol and the beta tensor of the two entities might reinforce or cancel each other. PMID- 26996993 TI - Construction and expression of an anti-VEGFR2 Nanobody-Fc fusionbody in NS0 host cell. AB - Angiogenesis is the formation of new blood vessels which is involved in migration, growth and differentiation of endothelial cells. This process regularly occurs during growth and development in children however, in adults is usually part of a disease process such as cancer. The vascular endothelial growth factor (VEGF) is a vital player in the vascular development and angiogenesis in physiological and pathological processes. Camelid's immune system has unique antibodies which are composed of only a heavy chain homodimer and the variable domain (VHH, Nanobody). Nanobodies are small, around 15 kDa and stable. In this study, we engineered and constructed a new Nanobody-Fc fusion protein (fusionbody) composed of an anti-VEGFR2 Nanobody and an Fc fragment of human IgG1 antibody. The recombinant vector was transfected into NS0 host cells. Stable producer clones were developed and the recombinant fusionbody was expressed and purified. Functional assay showed the anti-VEGFR2 fusionbody could bind to VEGFR2 on cell surface via VHH part and could mediate killing the targeted cells through direct cell death and complement-dependent cytotoxicity (CDC). PMID- 26996995 TI - The transcription factor Pf-POU3F4 regulates expression of the matrix protein genes Aspein and Prismalin-14 in pearl oyster (Pinctada fucata). AB - Matrix proteins play key roles in shell formation in the pearl oyster, but little is known about how these proteins are regulated. Here, two POU domain family members, Pf-POU2F1 and Pf-POU3F4, were cloned and characterized. Functional domain analysis revealed that both them have conserved POUS and POUH domains; these domains are important for transcription factor function. The tissue distributions of Pf-POU2F1 and Pf-POU3F4 mRNAs in pearl oyster revealed different expression patterns, and the expression of Pf-POU3F4 mRNA was relatively high in the mantle. The promoters of the matrix protein genes Aspein and Prismalin-14 were cloned using genome-walking PCR. Relatively high transcriptional activities of these promoters were detected in HEK-293T cells. In transient co-transfection assays, Pf-POU3F4 greatly up-regulated the promoter activities of the Aspein and Prismalin-14 genes in a dose-dependent manner. Structural integrity of Pf-POU3F4 was essential for its activation function. One region of the Aspein gene promoter, -181 to -77 bp, and two binding sites in the Prismalin-14 gene promoter, -359 to -337 bp and -100 to -73 bp, were required for activation of Pf POU3F4. An electrophoresis mobility shift assay demonstrated that Pf-POU3F4 directly bound these sites. Pf-POU3F4 knockdown led to a decrease in Aspein and Prismalin-14 gene expression. Furthermore, expression levels for the Pf-POU3F4 gene were similar to those of the Aspein and Prismalin-14 genes during five development stages. Taken together, these results suggest that the transcription factor Pf-POU3F4 regulates expression of the matrix protein genes Aspein and Prismalin-14 in pearl oyster. DATABASE: The nucleotide sequence data of Pf-POU2F1 is available in the GenBank databases under the accession number KM588196. The nucleotide sequence data of Pf-POU3F4 is available in the GenBank databases under the accession number KM519606. The nucleotide sequence data of Aspein gene promoter is available in the GenBank databases under the accession number KM519607. The nucleotide sequence data of Prismalin-14 gene promoter is available in the GenBank databases under the accession number KM519601. PMID- 26996996 TI - Visible-light-driven photocatalytic water oxidation catalysed by iron-based metal organic frameworks. AB - An iron-based metal-organic framework, MIL-101(Fe), promotes photocatalytic water oxidation to produce oxygen from aqueous silver nitrate solution under visible light irradiation. The finely dispersed iron-oxo clusters embedded as nodes of the porous framework would contribute importantly to the efficient promotion of the reaction as compared to bulk hematite (alpha-Fe2O3). PMID- 26996999 TI - Two-Dimensional Hollow TiO2 Nanoplates with Enhanced Photocatalytic Activity. AB - Two-dimensional anatase TiO2 hollow nanoplates were firstly synthesized through a facile synthesis route by using alpha-Fe2 O3 nanoplates as removable templates. Two-dimensional hollow TiO2 nanoplates with different ratios of anatase and rutile phases were obtained by adjusting the calcining temperature. The average diameters were around 600 nm, and the shell thickness was approximately 30 nm. The photocatalytic performance of TiO2 was investigated by decomposing rhodamine B under simulated sunlight. Among the TiO2 samples, the anatase TiO2 hollow nanoplates manifested a significant enhancement in the photocatalytic performances. The excellent catalytic performance can be attributed to the unique structure of the two-dimensional anatase TiO2 hollow nanoplates, including a large surface area and increased dye-photocatalyst contact areas as well as more active sites for photodegradation. PMID- 26996997 TI - Neuronal antibodies in pediatric epilepsy: Clinical features and long-term outcomes of a historical cohort not treated with immunotherapy. AB - OBJECTIVE: In autoimmune encephalitis the etiologic role of neuronal cell-surface antibodies is clear; patients diagnosed and treated early have better outcomes. Neuronal antibodies have also been described in patients with pediatric epilepsy without encephalitis. The aim was to assess whether antibody presence had any effect on long-term outcomes in these patients. METHODS: Patients (n = 178) were recruited between 1988 and 1992 as part of the prospective Dutch Study of Epilepsy in Childhood; none received immunotherapy. Healthy age-matched bone marrow donors served as controls (n = 112). All sera were tested for serum N methyl-d-aspartate receptor (NMDAR), alpha amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid receptor, leucine rich glioma inactivated 1, contactin associated protein like 2 (CASPR2), contactin-2, glutamic acid decarboxylase, and voltage gated potassium channel (VGKC)-complex antibodies by standard techniques. No cerebrospinal fluid (CSF) samples were available. Results were correlated with clinical data collected over 15 years. RESULTS: Seventeen patients (9.5%) were positive for VGKC complex (n = 3), NMDAR (n = 7), CASPR2 (n = 4), and contactin-2 (n = 3), compared to three (3/112; 2.6%) healthy controls (VGKC complex [n = 1], NMDAR [n = 2]; p = 0.03; Fisher's exact test). Titers were relatively low (<=1:100 for cell-surface antibodies), but 8 (47%) of the 17 positive samples bound to the surface of live hippocampal neurons consistent with a potential pathogenic antibody. Preexisting cognitive impairment was more frequent in antibody-positive patients (9/17 vs. 33/161; p = 0.01). Fourteen antibody positive patients were treated with standard antiepileptic drugs (AEDs); three (17%) became intractable but this was not different from the 16 (10%) of 161 antibody-negative patients. In 96 patients with available follow-up samples at 6 and/or 12 months, 6 of 7 positive antibodies had disappeared and, conversely, antibodies had appeared for the first time in a further 7 patients. SIGNIFICANCE: Neuronal antibodies were found at low levels in 9.5% of patients with new-onset pediatric epilepsy but did not necessarily persist over time, and the development of antibodies de novo in later samples suggests they could be due to a secondary response to neuronal damage or inflammation. Moreover, as the response to standard AEDs and the long-term outcome did not differ from those of antibody negative pediatric patients, these findings suggest that routine neuronal antibody testing is unlikely to be helpful in pediatric epilepsy. However, the higher incidence of preexisting cognitive problems in the antibody-positive group, the CASPR2 and contactin-2 antibodies in 7 of 17 patients, and the binding of 8 of 17 of serum samples to live hippocampal neurons suggest that neuronal antibodies, even if secondary, could contribute to the comorbidities of pediatric epilepsy. PMID- 26996998 TI - Assisted or Protected Mealtimes? Exploring the impact of hospital mealtime practices on meal intake. AB - AIMS: To evaluate the impact of mealtime practices (meal time preparation, assistance and interruptions) on meal intake of inpatients in acute hospital wards. BACKGROUND: It is common for patients to eat poorly while in hospital, related to patient and illness factors and possibly mealtime practices. Few studies have quantified the impact of mealtime practices on the meal intake of hospital patients. DESIGN: Cross-sectional study. METHODS: Structured observations were conducted at 601 meals across four wards (oncology, medical and orthopaedic and vascular surgical) during 2013. Each ward was observed by two dietitians and/or nurses for two breakfasts, lunches and dinners over 2 weeks. Data were collected on patient positioning, mealtime assistance, interruptions and meal intake (visual estimate of plate waste). Associations between mealtime practices and 'good' intake (prospectively defined as >=75% of meal) were identified using chi-squared tests. RESULTS: Sitting up for the meal was associated with good intake, compared with lying in bed. Timely mealtime assistance (within 10 minutes) was associated with good intake, compared with delayed or no assistance. Mealtime interruptions had no impact on intake. Forty percent of patients (n = 241) ate half or less of their meal, with 10% (n = 61) eating none of the meal provided. CONCLUSION: Timely mealtime assistance and positioning for the meal may be important factors that facilitate intake among hospital patients, while mealtime interruptions appeared to have no impact on intake. To improve intake of older inpatients, mealtime programmes should focus on 'assisted mealtimes' rather than only Protected Mealtimes. PMID- 26996992 TI - Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America. AB - INTRODUCTION: Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. METHODS: HIV positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. RESULTS: The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/uL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). CONCLUSIONS: HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation. PMID- 26997001 TI - To the editor Re: HIV care: A missed opportunity for immunization. PMID- 26997000 TI - Fatty Liver, Insulin Resistance, and Obesity: Relationships With Increase in Coronary Artery Calcium Over Time. AB - BACKGROUND: Nonalcoholic fatty liver disease, insulin resistance (IR), and obesity frequently coexist with type 2 diabetes mellitus (DM), but it is uncertain whether these risk factors for vascular disease contribute to a change in atherosclerosis over time, independently of DM status. HYPOTHESIS: We hypothesized that the combination of fatty liver, IR, and obesity would be associated with an increase in coronary artery calcium (CAC) score over time, independently of DM status, other cardiovascular risk factors, and medications. METHODS: Data were analyzed from a South Korean occupational cohort of 2175 people. The outcome was increase in cardiac computed tomography CAC score between baseline and follow-up. Insulin resistance was defined by homeostatic model assessment of insulin resistance (HOMA-IR) >=75th percentile and fatty liver by ultrasound. RESULTS: In 592 (27.2%) participants, CAC score increased from baseline (mean +/- SD; mean age at baseline, 44.8 +/- 5.5 years); and in 1583 subjects, CAC did not change or improved during follow-up (mean age, 41.6 +/- 5.6 years). Diabetes mellitus, HOMA-IR, fatty liver, and obesity prevalence were all higher (all P < 0.001) in participants whose CAC score increased from baseline. Adjusting for DM and potential confounders, the combination of IR, obesity, and fatty liver was independently associated with increase in CAC score over time (hazard ratio: 2.46, 95% confidence interval: 1.50-4.03). CONCLUSIONS: The combination of fatty liver, IR, and obesity is associated with progression of atherosclerosis over time independently of DM, cardiovascular risk factors, and all medications for cardiovascular disease and DM. PMID- 26997002 TI - Field randomized trial to evaluate the efficacy of the Leish-Tec(r) vaccine against canine visceral leishmaniasis in an endemic area of Brazil. AB - BACKGROUND: A canine vaccine remains a promising approach for effective control of visceral leishmaniasis (VL), given its complex epidemiology in areas where zoonotic VL is prevalent. Leish-Tec((r)) is a recombinant vaccine, based on the Leishmania A2 antigen, against canine VL (CVL). It is, since 2014, the single commercial vaccine licensed in Brazil. Here, Leish-Tec((r)) efficacy was estimated through a randomized field trial (RFT), in a highly VL endemic area. METHODS: The RFT was conducted from 2008 to 2010 in an endemic area of southeastern Brazil, presenting a CVL seroprevalence of 41.9%. Eight hundred forty-seven seronegative dogs were randomly selected to receive Leish-Tec((r)) (n=429) or placebo (n=418). Animals were followed up by clinical, serological, and parasitological exams for 18 months. The CVL incidence in both groups was compared through proportion analysis. RESULTS: A significant reduction in the number of cases of CVL was observed in the vaccine group, as compared with the placebo group, whether efficacy was estimated according to parasitological results (71.4%; 95% CI: 34.9-87.3%; p=0.001; risk ratio=0.287), by adding results of xenodiagnosis and parasitological exams (58.1%; 95% CI: 26.0-76.3%; p=0.002; risk ratio=0.419). Among the animals that converted to a positive anti-A2 serology, efficacy reached 80.8% (95% CI: 37.6-94.1%, p=0.001; risk ratio=0.192). Xenodiagnosis has detected a reduction of 46.6% (p=0.05) in transmission to sand flies from vaccinated animals presenting anti-A2 positive serology. CONCLUSION: The Leish-Tec((r)) vaccine proved significantly effective for prophylaxis of CVL, after natural challenge assured by transmission of Leishmania parasites, in a highly endemic area. Noteworthy, this report has unveiled the complexity of performing a RFT for anti-CVL vaccines in Brazil, which may be helpful for designing of future studies. PMID- 26997003 TI - Using AGREE II to Evaluate the Quality of Traditional Medicine Clinical Practice Guidelines in China. AB - OBJECTIVE: To evaluate/assess the quality of the Clinical Practice Guidelines (CPGs) of traditional medicine in China. METHODS: We systematically searched the literature databases WanFang Data, VIP, CNKI and CBM for studies published between 1978 and 2012 to identify and select CPGs of traditional medicine. We used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to evaluate these guidelines. RESULTS: A total of 75 guidelines were included, of which 46 guidelines (62%) were on Traditional Chinese Medicine, 19 (25%) on Chinese Integrated Medicine, and 10 (13%) on Uyghur Medicine. Most traditional medicine CPGs published in domestic journals scored <20% (range: 0 63%). Eleven (14%) CPGs were developed following the methodology of evidence based medicine. In each domain of AGREE II, traditional Medicine CPGs performed clearly better than international CPGs. The same trend was seen in guidelines of Modern Medicine. CONCLUSIONS: An increasing amount of CPGs are being published, but their quality is low. Referring to the key points of international guidelines development, supervision through AGREE II, cooperating with international groups and exploring the strategy of guideline development could improve the quality of CPGs on traditional medicine. This article is protected by copyright. All rights reserved. PMID- 26997004 TI - Unravelling the health impact of climate change. PMID- 26997005 TI - Gamma glutamyl transferase: A novel cardiovascular outfit for an old liver test. PMID- 26997006 TI - Importance of reporting sequence & serological data from mumps outbreaks in unvaccinated populations. PMID- 26997008 TI - Scope of translational research focusing rural areas. PMID- 26997007 TI - Postural & striatal deformities in Parkinson's disease: Are these rare? AB - Parkinson's disease (PD) is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS) and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD. PMID- 26997009 TI - Sickle cell disease in India: A perspective. PMID- 26997010 TI - Putting tobacco harm reduction in perspective: is it a viable alternative? PMID- 26997012 TI - Cross-neutralization between three mumps viruses & mapping of haemagglutinin neuraminidase (HN) epitopes. AB - BACKGROUND & OBJECTIVES: The reports from the countries where mumps vaccine is given as routine immunization suggest differences in mumps virus neutralizing antibody titres when tested with vaccine and wild type viruses. Such reports are unavailable from countries like India where mumps vaccine is not included in routine immunization. We, therefore, undertook this study to understand the cross neutralization activity of Indian mumps viruses. METHODS: By using commercial mumps IgG enzyme immunoassay (EIA) and a rapid focus reduction neutralization test (FRNT), a panel of serum samples was tested. The panel consisted of 14 acute and 14 convalescent serum samples collected during a mumps outbreak and 18 archived serum samples. Two wild types (genotypes C and G) and Leningrad-Zagreb vaccine strain (genotype N) were used for the challenge experiments and FRNT titres were determined and further compared. The HN protein sequence of three mumps viruses was analyzed for the presence of key epitopes. RESULTS: All serum samples effectively neutralized mumps virus wild types and a vaccine strain. However, significantly lower FRNT titres were noted to wild types than to vaccine strain (P<0.05). The comparison between EIA and FRNT results revealed 95.6 per cent agreement. No amino acid changes were seen in the epitopes in the Indian wild type strains. All potential N-linked glycosylation sites were observed in Indian strains. INTERPRETATION & CONCLUSIONS: Good cross-neutralization activity was observed for three mumps virus strains, however, higher level of FRNT titres was detected for mumps virus vaccine strain compared to Indian wild type isolates. PMID- 26997011 TI - Role of gamma-glutamyl transferase levels in prediction of high cardiovascular risk among patients with non-alcoholic fatty liver disease. AB - BACKGROUND & OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an important cause of elevated liver functions. There is evidence showing an association between NAFLD and subclinical atherosclerosis independent of traditional risk factors. We undertook this retrospective study to determine the association of Framingham cardiovascular risk scoring system with liver function tests and inflammatory markers and to find the role of liver function tests in determination of CVD risk among non-obese and non-diabetic subjects with non alcoholic fatty liver disease. METHODS: A total of 2058 patients were included in the study. Framingham cardiovascular risk scoring was done of all patients according to the age, gender, systolic blood pressure, serum total cholesterol and HDL cholesterol levels, smoking and antihypertensive medication history. Liver function test, lipid profile, insulin, uric acid, ferritin levels, etc. were determined. RESULTS: According to the ultrasonography findings, patients were grouped as without any fatty infiltration of the liver (control group) (n=982), mild (n= 473), moderate (n=363) and severe fatty liver disease (n= 240) groups. In severe fatty liver disease group, the mean Framingham cardiovascular risk score was significantly higher than that of other groups. t0 here was a positive correlation between GGT, uric acid and ferritin levels with Framingham cardiovascular score. In multivariate analysis, high GGT levels were positively associated with high-risk disease presence (OR: 3.02, 95% CI: 2.62-3.42) compared to low GGT levels independent of the age and sex. INTERPRETATION & CONCLUSIONS: Cardiovascular disease risk increases with the presence and stage of fatty liver disease. Our findings showed a positive correlation between elevated GGT levels and Framingham cardiovascular risk scoring system among non-diabetic, non-obese adults which could be important in clinical practice. Though in normal limits, elevated GGT levels among patients with fatty liver disease should be regarded as a sign of increased cardiovascular disease risk. Larger studies are warranted to elucidate the role of GGT in prediction of cardiovascular risk. PMID- 26997013 TI - Novel ATRX gene damaging missense mutation c.6740A>C segregates with profound to severe intellectual deficiency without alpha thalassaemia. AB - BACKGROUND & OBJECTIVES: ATRX is a recessive X-linked intellectual deficiency (X LID) gene causing predominately alpha-thalassaemia with a wide and clinically heterogeneous spectrum of intellectual deficiency syndromes. Although alpha thalassaemia is commonly present, some patients do not express this sign despite the ATRX gene being altered. Most pathological mutations have been localized in two different major domains, the helicase and the plant homeo-domain (PHD)-like domain. In this study we examined a family of three males having an X-linked mental deficiency and developmental delay, and tried to establish a genetic diagnosis while discussing and comparing the phenotype of our patients to those reported in the literature. METHODS: Three related males with intellectual deficiency underwent clinical investigations. We performed a karyotype analysis, CGH-array, linkage study, and X-exome sequencing in the index case to identify the genetic origin of this disorder. The X-inactivation study was carried out in the mother and Sanger sequencing was achieved in all family members to confirm the mutation. RESULTS: a0 novel ATRX gene missense mutation (p.His2247Pro) was identified in a family of two uncles and their nephew manifesting intellectual deficiency and specific facial features without alpha-thalassaemia. The mutation was confirmed by Sanger sequencing. It segregated with the pathological phenotype. The mother and her two daughters were found to be heterozygous. INTERPRETATION & CONCLUSIONS: The novel mutation c.6740A>C was identified within the ATRX gene helicase domain and confirmed by Sanger sequencing in the three affected males as well as in the mother and her two daughters. This mutation was predicted to be damaging and deleterious. The novel mutation segregated with the phenotype without alpha-thalassaemia and with non-skewed X chromosome. PMID- 26997014 TI - Comparison of nested-multiplex, Taqman & SYBR Green real-time PCR in diagnosis of amoebic liver abscess in a tertiary health care institute in India. AB - BACKGROUND & OBJECTIVES: Amoebiasis is a common parasitic infection caused by Entamoeba histolytica and amoebic liver abscess (ALA) is the most common extraintestinal manifestation of amoebiasis. The aim of this study was to standardise real-time PCR assays (Taqman and SYBR Green) to detect E. histolytica from liver abscess pus and stool samples and compare its results with nested multiplex PCR. METHODS: Liver abscess pus specimens were subjected to DNA extraction. The extracted DNA samples were subjected to amplification by nested multiplex PCR, Taqman (18S rRNA) and SYBR Green real-time PCR (16S-like rRNA assays to detect E. histolytica/E. dispar/E. moshkovskii). The amplification products were further confirmed by DNA sequence analysis. Receiver operator characteristic (ROC) curve analysis was done for nested-multiplex and SYBR Green real-time PCR and the area under the curve was calculated for evaluating the accuracy of the tests to dignose ALA. RESULTS: In all, 17, 19 and 25 liver abscess samples were positive for E. histolytica by nested-multiplex PCR, SYBR Green and Taqman real-time PCR assays, respectively. Significant differences in detection of E. histolytica were noted in the real-time PCR assays evaluated ( P<0.0001). The nested-multiplex PCR, SYBR Green real-time PCR and Taqman real time PCR evaluated showed a positivity rate of 34, 38 and 50 per cent, respectively. Based on ROC curve analysis (considering Taqman real-time PCR as the gold standard), it was observed that SYBR Green real-time PCR was better than conventional nested-multiplex PCR for the diagnosis of ALA. INTERPRETATION & CONCLUSIONS: Taqman real-time PCR targeting the 18S rRNA had the highest positivity rate evaluated in this study. Both nested multiplex and SYBR Green real-time PCR assays utilized were evaluated to give accurate results. Real-time PCR assays can be used as the gold standard in rapid and reliable diagnosis, and appropriate management of amoebiasis, replacing the conventional molecular methods. PMID- 26997015 TI - Preparation & in vitro evaluation of 90Y-DOTA-rituximab. AB - BACKGROUND & OBJECTIVES: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. METHODS: Rituximab was conjugated with p-SCN-Bn DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. RESULTS: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37 degrees C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 +/- 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 +/- 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. INTERPRETATION & CONCLUSIONS: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the radiolabelled conjugate suggesting the potential uitability of the formulation as a radiopharmaceutical for therapy of NHL. PMID- 26997016 TI - Evaluation of activity of hypothalamo-pituitary-gonadal axis in postmenopausal women suffering from severe acute illness. AB - BACKGROUND & OBJECTIVES: Postmenopausal women constitute an ideal model for studying the extent of hypothalamo-pituitary gonadal (HPG) axis suppression in critical illness as the gonadotropins are normally high and non-cyclical in them. The objective was to assess the impact of acute severe illness in postmenopausal women on the HPG axis and the activities of the hypothalamo-pituitary-adrenal (HPA), the hypothalamo- pituitary-thyroid (HPT) axes; and levels of serum prolactin, by comparison between critically ill postmenopausal women and otherwise healthy postmenopausal women. METHODS: Thirty five consecutive postmenopausal women older than 60 yr admitted to medical intensive care with a s0 implified a0 cute p0 hysiology s0 core II (SAPS II) more than 30 were included. On day five of their in-hospital stay, blood samples were collected for oestradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol, androstenedione, prolactin and thyroid profile. Thirty five apparently healthy postmenopausal women were selected as controls. RESULTS: Levels of LH, FSH, thyrotropin, free thyroxin (fT 4 ) and free tri-iodothyronine (fT 3 ) were lower while oestradiol, cortisol and dehydroepiandrosterone were higher among patients in comparison to healthy controls. Prolactin levels were similar in patients and controls. Among sick patients both FSH and fT 4 showed a negative correlation ( P<0.05) with the SAPS II score. INTERPRETATION & CONCLUSIONS: In critically ill postmenopausal women, paradoxically elevated oestrogen levels despite gonadotropin suppression suggests a non-ovarian origin. Prolactin remained unaltered in patients despite their illness, possibly reflecting atrophy of lactotrophs in menopause. PMID- 26997017 TI - Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for rapid diagnosis of neonatal sepsis. AB - BACKGROUND & OBJECTIVES: The difficulties in diagnosis of neonatal sepsis are due to varied clinical presentation, low sensitivity of blood culture which is considered the gold standard and empirical antibiotic usage affecting the outcome of results. Though polymerase chain reaction (PCR) based detection of bacterial 16S rRNA gene has been reported earlier, this does not provide identification of the causative agent. In this study, we used restriction fragment length polymorphism (RFLP) of amplified 16S rRNA gene to identify the organisms involved in neonatal sepsis and compared the findings with blood culture. METHODS: Blood samples from 97 neonates were evaluated for diagnosis of neonatal sepsis using BacT/Alert (automated blood culture) and PCR-RFLP. RESULTS: Bacterial DNA was detected by 16S rRNA gene PCR in 55 cases, while BacT/Alert culture was positive in 34 cases. Staphylococcus aureus was the most common organism detected with both methods. Klebsiella spp. was isolated from four samples by culture but was detected by PCR-RFLP in five cases while Acinetobacter spp. was isolated from one case but detected in eight cases by PCR-RFLP. The sensitivity of PCR was found to be 82.3 per cent with a negative predictive value of 85.7 per cent. Eighty of the 97 neonates had prior exposure to antibiotics. INTERPRETATION & CONCLUSIONS: The results of our study demonstrate that PCR-RFLP having a rapid turnaround time may be useful for the early diagnosis of culture negative neonatal sepsis. PMID- 26997018 TI - Prevalence of human papillomavirus infection & cervical abnormalities in HIV positive women in eastern India. AB - BACKGROUND & OBJECTIVES: India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. METHODS: We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. RESULTS: Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age <= 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 <= 350/ul [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 <= 350/ul [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. INTERPRETATION & CONCLUSIONS: Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women. PMID- 26997019 TI - Phage therapy of staphylococcal chronic osteomyelitis in experimental animal model. AB - BACKGROUND & OBJECTIVES: Methicillin resistant Staphylococcus aureus (MRSA) are the commonest cause of osteomyelitis. The aim of this study was to evaluate the role of an alternative therapy i.e. application of S. aureus specific bacteriophages in cases of osteomyelitis caused by MRSA in animal model. METHODS: Twenty two rabbits were included in this study. The first two rabbits were used to test the safety of phage cocktail while the remaining 20 rabbits were divided into three groups; group A (n=4) to assess the establishment of osteomyelitis; group B (n=4) osteomyelitis developed but therapy started only after six weeks; and group C (n=12) osteomyelitis developed and therapy started after three weeks. Groups B and C rabbits were treated with four doses of cocktail of seven virulent bacteriophages at the interval of 48 h. Comparison between three groups was made on the basis of observation of clinical, radiological, microbiological, and histopathological examinations. RESULTS: Experimental group rabbits recovered from the illness in the subsequent two weeks of the therapy. Appetite and activity of the rabbits improved, local oedema, erythema and induration subsided. There were minimal changes associated with osteomyelitis in X-ray and histopathology also showed no signs of infection with new bone formation. Control B group rabbits also recovered well from the infection. INTERPRETATION & CONCLUSIONS: The present study shows a potential of phage therapy to treat difficult infections caused by multidrug resistant bacteria. PMID- 26997020 TI - Profile of female patients seeking in-patient treatment for prescription opioid abuse from a tertiary care drug dependence treatment centre from India. AB - BACKGROUND & OBJECTIVES: There has been a limited focus on prescription drug abuse among women in the country. Choice of psychoactive substance, reasons for initiation and co-occurring disorders have been found to be different among men and women. The current study was aimed at studying the profile of female patients seeking in-patient treatment for prescription drug use over a period of five years at a tertiary care drug dependence treatment centre in India. METHODS: Case records of all female patients admitted with substance use disorder at a national level drug dependence treatment centre in north India across five years (between January 2008 and December 2012) were reviewed retrospectively to study their socio-demographic and clinical profile. The information was gathered using a semi structured proforma and detailed case records. Abstinence, relapse and retention rates were calculated. RESULTS: Over the five years, 31 female patients were admitted with prescription drug abuse. Of them, 12 (39%) used prescription opioids and 11 (36%) used prescription opioid along with benzodiazepines. Commonest prescription opioid was pentazocine used by 87 per cent of the women. Twenty two (71%) women were introduced to opioid by medical practitioners and commonest reason for introduction was pain (among 48%). Common co-occurring psychiatric diagnoses were depressive disorder (26%), cluster B traits/disorder (19%) and somatoform disorder (13%). Eight women did not complete treatment and left against medical advice. Thirteen women were advised maintenance treatment, and 70 per cent of them were retained for at least six months. INTERPRETATION & CONCLUSIONS: Our findings revealed a link between mental illness, pain and non medical use of prescription opioids among women. Majority of these women received opioids as a legitimate prescription form physician. Therefore, these legitimate prescribers should be trained for pain management to facilitate proper treatment of pain and to prevent the subsequent misuse of these medicines. Female patients with frequent pain complaints should be assessed for psychopathology while prescribing opioids. PMID- 26997021 TI - Substance abuse amongst the medical graduate students in a developing country. AB - BACKGROUND & OBJECTIVES: Substance abuse is found worldwide including among students. We carried out this study to estimate the prevalence of substance abuse among medical student studying in a medical college in north India. METHODS: Using a validated questionnaire a cross-sectional survey was conducted among 230 undergraduate and postgraduate medical students in a private medical college. RESULTS: The prevalence of substance abuse was 20.43 per cent (47/230) among medical students. An increase in substance abuse was observed in the latter years of medical education. A total of 43 of 47 (91.7%) students using these substances were aware of the ill effects. The most common reasons for substance use were relief from psychological stress (34/47, 72.4%) and occasional celebration (34/47, 72.4%). Of the 47 substance users, 28 (59.6%) made past attempts to quit the substance abuse. INTERPRETATION & CONCLUSIONS: Nearly one-fifth of medical students abuse at least one substance despite knowing the ill effects with the main predisposing factor being the psychological stress. PMID- 26997022 TI - Bayesian model, ecological factors & transmission of leprosy in an endemic area of South India. PMID- 26997023 TI - Drug resistance in Enterococcus species in a tertiary level hospital in Assam, India. PMID- 26997024 TI - Is the improved function of streptozotocin treated pancreas truly due to transdifferentiation/fusion of transplanted MSCs? PMID- 26997025 TI - Authors' response. PMID- 26997026 TI - Paediatric hypertension in Iraq. PMID- 26997027 TI - Authors' response. PMID- 26997028 TI - Bilateral acute ophthalmic artery occlusion in a case of giant cell arteritis. PMID- 26997029 TI - Disseminated nocardiosis in a patient with sarcoidosis. PMID- 26997030 TI - Erratum. PMID- 26997031 TI - Effectiveness of red blood cell exchange, partial manual exchange, and simple transfusion concurrently with iron chelation therapy in reducing iron overload in chronically transfused sickle cell anemia patients. AB - BACKGROUND: Chronic transfusion therapy (CTT) is indicated for stroke prevention in children with sickle cell anemia (SCA) and is complicated by iron overload and alloimmunization. CTT is performed by simple transfusion (ST), partial manual exchange (PME), or erythrocytapheresis (RCE). Although small case series have demonstrated RCE in combination with iron chelation therapy stabilizes and/or decreases ferritin, there are no reports comparing the effect of ST, PME, and RCE on liver iron concentration (LIC). CTT modality effect on serum ferritin and LIC were compared in SCA patients on iron chelation, with hemoglobin (Hb)S goal of 30%. STUDY DESIGN AND METHODS: Medical records of SCA patients on CTT and deferasirox (>=25 mg/kg/day) were retrospectively reviewed. Mean HbS%, change in ferritin and LIC, and alloimmunization rate were determined for each CTT group. RESULTS: Twenty-eight patients were included; six crossed over (one from ST to PME, one from ST to PME then to RCE, three from ST to RCE, and one from PME to RCE) to include 36 transfusion modality intervals. Median pretransfusion HbS% levels were 32.7% (ST), 36.2% (PME), and 34.7% (RCE; p = 0.732). Median ferritin changes were +15 (-17 to +45), +38 (+24 to +105), and -91 (-141 to -48) ng/mL/month (p = 0.003), and median LIC changes (available in 22 patient transfusion modality intervals) were +1.3 (-1.6 to +4.3), +2.3 (-6.5 to +8.9), and -5.7 (-10.7 to -0.5) mg/g/year (p = 0.024) in ST, PME, and RCE, respectively. There was no significant difference in alloimmunization rate between ST/PME and RCE groups. CONCLUSION: We recommend RCE plus chelation as an effective method for reducing iron overload, while maintaining HbS at 30% to 35%. PMID- 26997032 TI - Unfolded Maps for Quantitative Analysis of Cortical Lesion Location and Extent after Traumatic Brain Injury. AB - We aimed to generate two-dimensional (2D) unfolded cortical maps from magnetic resonance (MR) images to delineate the location of traumatic brain injury (TBI) induced cortical damage in functionally diverse cytoarchitectonic areas of the cerebral cortex, and to predict the severity of functional impairment after TBI based on the lesion location and extent. Lateral fluid-percussion injury was induced in adult rats and T2 maps were acquired with magnetic resonance imaging (MRI) at 3 days post-TBI. Somatomotor deficits were assessed based on the composite neuroscore and beam balance test, and spatial learning was assessed in the Morris water maze. Animals were perfused for histology at 13 days post injury. A 2D template was generated by unfolding the cerebral cortex from 26 sections of the rat brain atlas, covering the lesion extent. Next, 2D unfolded maps were generated from T2 maps and thionin-stained histological sections from the same animals. Unfolding of the T2 maps revealed the lesion core in the auditory, somatosensory, and visual cortices. The unfolded histological lesion at 13 days post-injury was 12% greater than the MRI lesion at 3 days post-TBI, as the lesion area increased laterally and caudally; the larger the MRI lesion area, the larger the histological lesion area. Further, the larger the MRI lesion area in the barrel field of the primary somatosensory cortex (S1BF), upper lip of the primary somatosensory cortex (S1ULp), secondary somatosensory division (S2), and ectorhinal (Ect) and perirhinal (PRh) cortices, the more impaired the performance in the beam balance and Morris water maze tests. Subsequent receiver operating characteristic analysis indicated that severity of the MRI lesion in S1ULp and S2 was a sensitive and specific predictor of poor performance in the beam balance test. Moreover, MRI lesions in the S1ULp, S2, S1BF, and Ect and PRh cortices predicted poor performance in the Morris water maze test. Our findings indicate that 2D-unfolded cortical maps generated from MR images delineate the distribution of cortical lesions in functionally different cytoarchitectonic regions, which can be used to predict the TBI-induced functional impairment. PMID- 26997033 TI - Spinosin, a C-glycoside flavonoid, enhances cognitive performance and adult hippocampal neurogenesis in mice. AB - Adult neurogenesis has received much attention due to its potential role in neurological or psychiatric disorders such as Alzheimer's disease. In the present study, we examined whether spinosin, a C-glycoside flavonoid from the seeds of Zizyphus jujuba var. spinosa, affects cognitive performance and adult hippocampal neurogenesis in normal naive mice. The subchronic administration of spinosin (5mg/kg) for 14days significantly increased the latency time in the passive avoidance task. Doublecortin and 5-bromo-2-deoxyuridine immunostaining revealed that the subchronic administration of spinosin (5mg/kg) significantly increased the proliferation and survival of neuronal cells and the number of immature neurons in the hippocampal dentate gyrus region. In addition, we observed an increase in the percentage of BrdU-incorporated cells co-localized with NeuN, a mature neuronal marker, which indicated that spinosin stimulates the differentiation of newly generated cells into mature neurons. Also, the subchronic treatment with spinosin (5mg/kg) increased the expression levels of phosphorylated extracellular-regulated kinase (ERK), phosphorylated cAMP response element-binding protein (CREB) and mature brain-derived neurotrophic factor (mBDNF) in the hippocampus. These findings demonstrate that spinosin has the potential for therapeutic use in treating the cognitive dysfunction observed in neurological or psychiatric disorders by up-regulating adult hippocampal neurogenesis or activating of the ERK-CREB-BDNF signaling pathway. PMID- 26997035 TI - Mite choice generates sex- and size-biased infection in Drosophila hydei. AB - Heterogeneities in parasite infection among conspecific hosts often manifest as sex- or size-biased infections, which are typically attributed to differential host susceptibility and exposure. Since parasite fitness is often tied to host quality, host preference by parasites is likely to be under strong selection. We test the hypothesis that host preference is sufficient to generate variability in infection rate among conspecifics. Specifically, we ask whether the mite Macrocheles muscaedomesticae is able to discriminate between Drosophila hydei hosts of different sex and size, while explicitly accounting for the potential confounding effects of these two factors. Our results indicate a preference for female hosts, but this preference appears to be driven by size and not sex per se. When differences in body size were controlled for, the sex-biased infection disappeared, while mites presented with the choice of two female flies of disparate sizes were more likely to select the larger host. Across the distribution of fly body weight in this study, mites preferentially attached to flies of intermediate size. This study provides evidence that mite choice for certain host types can play an important role in parasite transmission, even in the absence of differential susceptibility or exposure among hosts. PMID- 26997036 TI - MoS2 nanoflowers as high performance saturable absorbers for an all-fiber passively Q-switched erbium-doped fiber laser. AB - Strong saturable absorption was observed in MoS2 nanoflowers, which were synthesized by a facile solvothermal method. A MoS2 nanoflower-based saturable absorber with a high modulation depth of 51.8% and a large saturable intensity of 275.5 GW cm(-2) was introduced to the application of passively Q-switched fiber laser generation. Stable passively Q-switched fiber laser pulses at 1.56 MUm with a low threshold power of 16.10 mW, high signal-to-noise ratio of 52.5 dB and short pulse duration of 1.9 MUs were obtained. More importantly, a high output power of 3.10 mW related to a large pulse energy of about 51.84 nJ can be attained at a very low pump power. The efficiency of the laser reaches 4.71%, which is larger than that of the prepared layered MoS2 and recently reported MoS2 based passively Q-switching operations. Such results imply that the MoS2 nanoflowers are an excellent candidate for a saturable absorber in passively Q switched fiber lasers at a low pump intensity. PMID- 26997034 TI - Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention. AB - Intestinal function is primarily controlled by an intrinsic nervous system of the bowel called the enteric nervous system (ENS). The cells of the ENS are neural crest derivatives that migrate into and through the bowel during early stages of organogenesis before differentiating into a wide variety of neurons and glia. Although genetic factors critically underlie ENS development, it is now clear that many non-genetic factors may influence the number of enteric neurons, types of enteric neurons, and ratio of neurons to glia. These non-genetic influences include dietary nutrients and medicines that may impact ENS structure and function before or after birth. This review summarizes current data about gene environment interactions that affect ENS development and suggests that these factors may contribute to human intestinal motility disorders like Hirschsprung disease or irritable bowel syndrome. PMID- 26997037 TI - Anticonvulsant Efficacy in Sturge-Weber Syndrome. AB - OBJECTIVE: We analyzed individuals with epilepsy due to Sturge-Weber syndrome to determine which anticonvulsants provided optimal seizure control and which resulted in the fewest side effects. METHODS: One-hundred-eight records from a single center were retrospectively analyzed for Sturge-Weber syndrome brain involvement, epilepsy, Sturge-Weber syndrome neuroscores, and currently used anticonvulsants. RESULTS: Of the fourteen anticonvulsants that had been employed, the most often used agents were oxcarbazepine or carbamazepine, and levetiracetam. Individuals whose seizures at the most recent visit were fully controlled (seizure-free) for 6 months or longer were more likely to have ever tried, or currently used, oxcarbazepine or carbamazepine than those with uncontrolled seizures. Thirty-nine of 69 individuals (56.5%) were seizure-free with oxcarbazepine or carbamazepine history versus 11 of 35 individuals (31.4%) who had not taken these agents (P < 0.05); 38 of 62 patients (61.3%) were seizure free while currently taking these anticonvulsants versus 12 of 42 (28.6%) not taking them (P < 0.01). Patients with seizure control for 6 months or longer were less likely to have ever tried, or to currently be taking, levetiracetam than those without control. Sixteen of 56 individuals (28.6%) were seizure-free with levetiracetam history versus 34 of 48 (70.8%) without it (P < 0.001); 14 of 43 individuals (32.6%) were seizure-free and currently taking levetiracetam versus 36 of 61 (59.0%) not taking it (P < 0.01). When topiramate was added as second line medication, five of nine patients (55.6%) experienced decreased seizure severity, and worsening of glaucoma was not reported. CONCLUSIONS: Carbamazepine and oxcarbazepine were associated with better seizure control than levetiracetam in this Sturge-Weber syndrome cohort and so may be preferred as the initial therapy. When used as adjunctive therapy, topiramate was effective in this limited analysis without a clear increased incidence of glaucoma. PMID- 26997038 TI - Eye-Mouth Associated Movement in the Human Newborn and Very Young Infant. AB - BACKGROUND: The aim of this study is to demonstrate that goal-directed eye-mouth associated movement exists in the newborn and very young infant. METHODS: The participants were 17 healthy term newborns or very young infants whose ages at the time of the first examination ranged from 1 to 24 days. The examiner held the tip of an index finger 20 to 30 cm in front of a participant's mouth, then suddenly moved it directly toward the mouth. Thirteen of the participants were also examined with the examiner's palm as the visual stimulus. The response was judged to be positive if clear mouth opening was elicited as the fingertip or palm was approaching the mouth. RESULTS: In the examinations using a fingertip, the frequency of a positive response as to the total number of examinations in the different age groups within the first two months of life ranged between 43.9% and 48.8%, and precipitously decreased to 6.3% at two months of age. A positive response was not elicited from age three months. On the other hand, in the examinations using a palm, the frequency of a positive response was 5.0% in the newborns, and 6.7% in the infants aged between seven days and one month. A positive response was never obtained from two months of age. CONCLUSION: This study demonstrated that visually guided mouth opening toward an approaching target exists in the human newborn. The eye-mouth associated movement may be controlled through rudimentary but functional visuomotor circuits in the brain interconnecting different cortices. PMID- 26997082 TI - Sustainability of protocolized handover of pediatric cardiac surgery patients to the intensive care unit. AB - BACKGROUND: Transfer of patient care among clinicians (handovers) is a common source of medical errors. While the immediate efficacy of these initiatives is well documented, sustainability of practice changes that results in better processes of care is largely understudied. AIMS: The objective of the current investigation was to evaluate the sustainability of a protocolized handover process in pediatric patients from the operating room after cardiac surgery to the intensive care unit. METHODS: This was a prospective study with direct observation assessment of handover performance conducted in the cardiac ICU (CICU) of a free-standing, tertiary care children's hospital in the United States. Patient transitions from the operating room to the CICU, including the verbal handoff, were directly observed by a single independent observer in all phases of the study. A checklist of key elements identified errors classified as: (1) technical, (2) information omissions, and (3) realized errors. Total number of errors was compared across the different times of the study (preintervention, postintervention, and the current sustainability phase). RESULTS: A total of 119 handovers were studied: 41 preintervention, 38 postintervention, and 40 in the current sustainability phase. The median [Interquartile range (IQR)] number of technical errors was significantly reduced in the sustainability phase compared to the preintervention and postintervention phase, 2 (1-3), 6 (5-7), and 2.5 (2 4), respectively P = 0.0001. Similarly, the median (IQR) number of verbal information omissions was also significantly reduced in the sustainability phase compared to the preintervention and postintervention phases, 1 (1-1), 4 (3-5) and 2 (1-3), respectively. CONCLUSIONS: We demonstrate sustainability of an improved handover process using a checklist in children being transferred to the intensive care unit after cardiac surgery. Standardized handover processes can be a sustainable strategy to improve patient safety after pediatric cardiac surgery. PMID- 26997083 TI - Introduction. PMID- 26997085 TI - Novel Image Guidance Techniques for Portal Vein Targeting During Transjugular Intrahepatic Portosystemic Shunt Creation. AB - The most challenging part of transjugular intrahepatic portosystemic shunt creation is arguably the transvenous access from the hepatic vein to the portal vein. As experience and technology have evolved, the image guidance aspect of this critical step in the procedure has become more robust. Improved means to target the portal vein include both direct and indirect methods of portal vein opacification, cross-sectional imaging for both targeting and access, and novel use of transabdominal and intravascular ultrasound guidance. These techniques are described herein. PMID- 26997084 TI - The Transjugular Intrahepatic Portosystemic Shunt: Technique and Instruments. AB - Although transjugular intrahepatic portosystemic shunt (TIPS) was first described in 1971, it took 15 more years for technology, in the form of expandable metallic stents, to be developed to make TIPS a viable, widespread clinical procedure. Currently, expanded polytetrafluoroethylene-covered stent grafts that exhibit significantly greater long-term patency are used for TIPS creation by most interventionalists. TIPS creation requires specific interventional skills, tools, and devices for success. In the hands of skillful, experienced interventional radiologists, TIPS creation is performed safely and successfully in greater than 95% of cases. PMID- 26997086 TI - Transjugular Intrahepatic Portosystemic Shunt Creation With Embolization or Obliteration for Variceal Bleeding. AB - Variceal hemorrhage is a life-threatening sequela of liver cirrhosis that requires a careful and comprehensive approach to management. Transjugular intrahepatic portosystemic shunt creation with or without variceal embolization or obliteration represents a minimally invasive image-guided intervention used for the management of varices. This review focuses on the role of transjugular intrahepatic portosystemic shunt and embolization or obliteration in the setting of variceal hemorrhage, with an emphasis on the useful aspects of patient evaluation and selection, practical approaches to procedure planning and valuable elements of interventional technique, and clinical outcomes as they pertain to portal venous decompression and variceal embolotherapy. PMID- 26997087 TI - Evolving Indications for Tips. AB - Transjugular intrahepatic portosystemic shunt creation is a well-established therapy for refractory variceal bleeding and refractory ascites in patients who do not tolerate repeated large volume paracentesis. Experience and technical improvements including covered stents have led to improved TIPS outcomes that have encouraged an expanded application. Evidence for other less frequent indications continues to accumulate, including the indications of primary prophylaxis in patients with high-risk acute variceal bleeding, gastric and ectopic variceal bleeding, primary treatment of medically refractory ascites, recurrent refractory ascites following liver transplantation, hepatic hydrothorax, hepatorenal syndrome, Budd-Chiari syndrome, and portal vein thrombosis. Treatment of patients with high-risk acute variceal bleeding with early TIPS and using transjugular intrahepatic portosystemic shunts as a primary therapy rather than large volume paracentesis for refractory ascites would likely be the 2 circumstances that permit expansion in the frequency of TIPS procedures. The remaining populations discussed above are relatively rare. PMID- 26997088 TI - Thrombolysis and Transjugular Intrahepatic Portosystemic Shunt Creation for Acute and Subacute Portal Vein Thrombosis. AB - Catheter-based interventional therapy offers a safe and effective option for treatment of symptomatic portomesenteric venous thrombosis refractory to medical therapy. Various techniques and approaches have been described for thrombolysis and thrombectomy and re-establishing the portal venous flow for select populations. Early diagnosis and prompt treatment based on clinical presentation, imaging, and underlying anatomy are necessary to prevent long-term complications. This article describes various catheter-based approaches for treatment of acute and subacute portal vein thrombosis. PMID- 26997090 TI - Complications During Transjugular Intrahepatic Portosystemic Shunt Creation. AB - Transjugular intrahepatic portosystemic shunt (TIPS) creation is a widely adopted treatment for complications of portal hypertension, including variceal hemorrhage and refractory ascites. The creation of a TIPS requires establishing a pathway from the portal vein to a hepatic vein or inferior vena cava through hepatic parenchyma, using a stent or stent graft to sustain patency of this pathway. Because it is a technically challenging procedure and patients may be critically ill with severe comorbidities, the risk of procedural complications and mortality is substantial. This article discusses known complications of the TIPS procedure and ways to minimize their occurrence. PMID- 26997089 TI - Portal Vein Recanalization and Transjugular Intrahepatic Portosystemic Shunt Creation for Chronic Portal Vein Thrombosis: Technical Considerations. AB - Portal vein thrombosis (PVT) is common in cirrhotic patients and presents a challenge at the time of transplant. Owing to the increased posttransplant morbidity and mortality associated with complete PVT, the presence of PVT is a relative contraindication to liver transplantation at many centers. Our group began performing portal vein (PV) recanalization and transjugular intrahepatic portostystemic shunt placement (PVR-TIPS) several years ago to optimize the transplant candidacy of patients with PVT. The procedure has evolved to include transsplenic access to assist with recanalization, which is now our preferred method due to its technical success without significant added morbidity. Here, we describe in detail our approach to PVR-TIPS with a focus on the transsplenic method. The procedure was attempted in 61 patients and was technically successful in 60 patients (98%). After transitioning to transsplenic access to assist with recanalization, the technical success rate has improved to 100%. The recanalized portal vein and TIPS have maintained patency during follow-up, or to the time of transplant, in 55 patients (92%) with a mean follow-up of 16.7 months. In total, 23 patients (38%) have undergone transplant, all of whom received a physiologic anastomosis (end-to-end anastomosis in 22 of 23 patients, 96%). PVR-TIPS placement should be considered as an option for patients with chronic PVT in need of transplantation. Transsplenic access makes the procedure technically straightforward and should be considered as the primary method for recanalization. PMID- 26997091 TI - Techniques for Transjugular Intrahepatic Portosystemic Shunt Reduction and Occlusion. AB - Transjugular intrahepatic portosystemic shunts (TIPS) effectively lower portal pressure and are commonly used to manage selected patients with variceal bleeding. Unfortunately, significant consequences are not infrequently encountered as a result of this diversion of portal venous flow. These consequences include disabling hepatic encephalopathy as well as hepatic decompensation. To manage these complications, therapeutic options include TIPS reduction and TIPS occlusion. TIPS reduction is the favored technique because of the potential for venous thrombosis and recurrent variceal hemorrhage after acute TIPS occlusion. Techniques and indications for TIPS reduction and TIPS occlusion are reviewed. PMID- 26997092 TI - Post-Transjugular Intrahepatic Portosystemic Shunt Follow-Up and Management in the VIATORR Era. AB - The transjugular intrahepatic portosystemic shunt (TIPS) is a non-selective portosystemic shunt created using endovascular techniques. The first TIPS was performed in Germany in 1988. The VIATORR self-expandable PTFE covered stent graft (WL Gore, Flagstaff AZ) was approved by the FDA for a TIPS application in December of 2004. This stent-graft offers excellent shunt patency rates and it is possible that it has a beneficial effect on patient survival. Patient surveillance and post-procedural management have changed after the introduction of this stent-graft. This article presents the current management strategies that are followed at our Institution for patients who have undergone a TIPS procedure with a VIATORR stent graft including imaging follow-up, management of encephalopathy, medical management and nutritional aspects. PMID- 26997093 TI - Optogenetic dissection of ictal propagation in the hippocampal-entorhinal cortex structures. AB - Temporal lobe epilepsy (TLE) is one of the most common drug-resistant forms of epilepsy in adults and usually originates in the hippocampal formations. However, both the network mechanisms that support the seizure spread and the exact directions of ictal propagation remain largely unknown. Here we report the dissection of ictal propagation in the hippocampal-entorhinal cortex (HP-EC) structures using optogenetic methods in multiple brain regions of a kainic acid induced model of TLE in VGAT-ChR2 transgenic mice. We perform highly temporally precise cross-area analyses of epileptic neuronal networks and find a feed forward propagation pathway of ictal discharges from the dentate gyrus/hilus (DGH) to the medial entorhinal cortex, instead of a re-entrant loop. We also demonstrate that activating DGH GABAergic interneurons can significantly inhibit the spread of ictal seizures and largely rescue behavioural deficits in kainate exposed animals. These findings may shed light on future therapeutic treatments of TLE. PMID- 26997094 TI - Direct measurement of the tryptophan-mediated photocleavage kinetics of a protein disulfide bond. AB - Disulfide cleavage is one of the major causes underlying ultraviolet (UV) light induced protein damage. While previous studies have provided strong evidence to support the notion that this process is mediated by photo-induced electron transfer from the excited state of an aromatic residue (e.g., tryptophan) to the disulfide bond, many mechanistic details are still lacking. For example, we do not know how quickly this process occurs in a protein environment. Herein, we design an experiment, which uses the unfolding kinetics of a protein as an observable, to directly assess the kinetics and mechanism of photo-induced disulfide cleavage. Our results show that this disulfide bond cleavage event takes place in ~2 MUs via a mechanism involving electron transfer from the triplet state of a tryptophan (Trp) residue to the disulfide bond. Furthermore, we find that one of the photoproducts of this reaction, a Trp-SR adduct, is formed locally, thus preventing the protein from re-cross-linking. Taken together, these findings suggest that a Trp-disulfide pair could be used as a photo-trigger to initiate protein folding dynamics and control the biological activities of disulfide-containing peptides. PMID- 26997096 TI - Prolonged Electron Lifetime in Ordered TiO2 Mesophyll Cell-Like Microspheres for Efficient Photocatalytic Water Reduction and Oxidation. AB - Mesoporous integrated TiO2 spheres composed of numerous orderly arranged nanocrystals with a reduced lattice-lattice interface connection, display an almost four times longer electron lifetime (350 ps) than the randomly aggregated nanoparticles (80 ps), and hence enhance the corresponding photocatalytic H2 and O2 generation. PMID- 26997095 TI - A compound synonymous mutation c.474G>A with p.Arg578X mutation in SPINK5 causes splicing disorder and mild phenotype in Netherton syndrome. PMID- 26997097 TI - Integration of antimicrobial pectin-based edible coating and active modified atmosphere packaging to preserve the quality and microbial safety of fresh-cut persimmon (Diospyros kaki Thunb. cv. Rojo Brillante). AB - BACKGROUND: The greatest hurdle to the commercial marketing of fresh-cut fruits is related to their higher susceptibility to enzymatic browning, tissue softening, and microbial growth. The aim of this study was to test the efficacy of a pectin-based edible coating and low oxygen modified atmosphere packaging (MAP) to control enzymatic browning and reduce microbial growth of fresh-cut 'Rojo Brillante' persimmon. The survival of Escherichia coli, Salmonella enteritidis and Listeria monocytogenes artificially inoculated on fresh-cut fruit was also assessed. The pectin coating was amended with 500 IU mL-1 nisin (NI) as antimicrobial agent and 10 g kg-1 citric acid and 10 g kg-1 calcium chloride as anti-browning and firming agents, respectively. Persimmon slices were dipped in the coating or in water (control) and packed under 5 kPa O2 (MAP) or in ambient atmosphere for up to 9 days at 5 degrees C. Microbial growth, package gas composition, colour, firmness, polyphenol oxidase activity, visual quality and overall sensory flavour of persimmon slices were measured during storage. RESULTS: Coating application combined with active MAP significantly reduced the CO2 emission and O2 consumption in the package. The coating was effective in reducing browning and also inhibited the growth of mesophilic aerobic bacteria. Coating also reduced the populations of E. coli, S. enteritidis and L. monocytogenes. CONCLUSION: The combination of the pectin-based edible coating and active MAP proved to be the most effective treatment to maintain the sensory and microbiological quality of persimmon slices for more than 9 days of storage. (c) 2016 Society of Chemical Industry. PMID- 26997098 TI - A multiplex PCR assay for the detection and quantification of Sclerotinia sclerotiorum and Botrytis cinerea. AB - Traditional culture methods for identifying the plant fungal pathogens Sclerotinia sclerotiorum (Lib.) de Bary and Botrytis cinerea Pers.:Fr. are slow and laborious. The goal of this study was to develop a multiplex real-time PCR (qPCR) assay to detect and quantify DNA from S. sclerotiorum and B. cinerea. A primer set (SsIGS_5) for S. sclerotiorum was designed that targeted the intergenic spacer (IGS) regions of the ribosomal DNA. Addition of a probe to the assay increased its specificity: when the primer/probe set was tested against 21 fungal species (35 strains), amplification was detected from all S. sclerotiorum strains and no other species. For qPCR, the SsIGS_5 primer and probe set exhibited a linear range from 7.0 ng to 0.07 pg target DNA (R(2) = 0.99). SsIGS_5 was then multiplexed with a previously published primer/probe set for B. cinerea to develop a high-throughput method for the detection and quantification of DNA from both pathogens. When multiplexed, the sensitivity and specificity of both assays were not different from individual qPCR reactions. The multiplex assay is currently being used to detect and quantify S. sclerotiorum and B. cinerea DNA from aerosol samples collected in commercial seed alfalfa fields. SIGNIFICANCE AND IMPACT OF THE STUDY: A primer and probe set for the quantification of Sclerotinia sclerotiorum DNA in a PCR assay was developed. The probe-based nature of this assay signifies an improvement over previous assays for this species by allowing multiplex reactions while maintaining high sensitivity. The primer/probe set was used in a multiplex real-time PCR assay for the quantification of S. sclerotiorum and Botrytis cinerea DNA, enabling rapid analysis of environmental samples. In crops susceptible to both pathogens, this multiplex assay can be used to quickly quantify the presence of each pathogen. PMID- 26997099 TI - Phenotypical and biochemical characterisation of resistance for parasitic weed (Orobanche foetida Poir.) in radiation-mutagenised mutants of chickpea. AB - BACKGROUND: Some radiation-mutagenised chickpea mutants potentially resistant to the broomrape, Orobanche foetida Poir., were selected through field trials. The objectives of this work were to confirm resistance under artificial infestation, in pots and mini-rhizotron systems, and to determine the developmental stages of broomrape affected by resistance and the relevant resistance mechanisms induced by radiation mutagenesis. RESULTS: Among 30 mutants tested for resistance to O. foetida, five shared strong resistance in both pot experiments and mini-rhizotron systems. Resistance was not complete, but the few individuals that escaped resistance displayed high disorders of shoot development. Results demonstrated a 2-3-fold decrease in stimulatory activity of root exudates towards broomrape seed germination in resistant mutants in comparison with non-irradiated control plants and susceptible mutants. Resistance was associated with an induction of broomrape necrosis early during infection. When infested, most of the resistant mutants shared enhanced levels of soluble phenolic contents, phenylalanine ammonia lyase activity, guaiacol peroxidase activity and polyphenol oxidase activity, in addition to glutathione and notably ascorbate peroxidase gene expression in roots. CONCLUSION: Results confirmed enhanced resistance in chickpea radiation mutagenised mutants, and demonstrated that resistance is based on alteration of root exudation, presumed cell-wall reinforcement and change in root oxidative status in response to infection. (c) 2016 Society of Chemical Industry. PMID- 26997100 TI - Management of stage IIIA (N2) non-small cell lung cancer: A transatlantic perspective. PMID- 26997101 TI - The internal mammary artery perforator flap and its subtypes in the reconstruction of median sternotomy wounds. AB - OBJECTIVE: To determine the feasibility of using the internal mammary artery perforator (IMAP) flap for superficial and deep sternal wound breakdowns. METHODS: This was a retrospective case review of 9 patients with sternal wound dehiscence over an 18-month period between 2013 and 2015. Seven of the 9 patients received a single IMAP flap to cover full-length sternal wounds, including 4 with a fasciocutaneous flap and 3 with a musculocutaneous flap. RESULTS: All of the patients were male, with a mean age of 68 years. The mean number of perforators was 1.3, with a mean perforator diameter of 1.5 mm. In all cases, the torsion angle was 80 degrees, with a translational pedicle movement of 1 to 2 cm. There were no instances of total flap failure and only 2 cases of partial flap necrosis, which were managed conservatively. One flap, performed when both internal mammary arteries had been harvested previously, showed complete survival. CONCLUSIONS: The IMAP flap has an advantage in its the ability to reconstruct the entire length of a sternotomy wound from the suprasternal notch to the xiphisternum with relatively minimal dissection and morbidity compared with more conventional flaps such as pectoralis major, rectus, and omental flaps. Nevertheless, caveats for its use remain, such as in patients with vasopressor therapy and the resulting subclavicular scar, which is unaesthetic in women. Overall, the IMAP flap is an attractive reconstructive tool specifically in stable male patients with noninfected sternotomy wound dehiscence with a defect width of up to 7 cm. In this patient subset, it is the ideal first-line reconstructive tool. PMID- 26997102 TI - If the shoe fits, choose it: Tailored strategy for postcoarctation complications. PMID- 26997103 TI - The necessity of self-promotion: A key component to early practice building. PMID- 26997105 TI - Take the long way home: Behaviour of a neotropical frog, Allobates femoralis, in a detour task. AB - Detour behaviour, an individual's ability to reach its goal by taking an indirect route, has been used to test spatial cognitive abilities across a variety of taxa. Although many amphibians show a strong homing ability, there is currently little evidence of amphibian spatial cognitive flexibility. We tested whether a territorial frog, Allobates femoralis, can flexibly adjust its homing path when faced with an obstacle. We displaced male frogs from their calling sites into the centre of circular arenas and recorded their escape routes. In the first experiment we provided an arena with equally high walls. In the second experiment we doubled the height of the homeward facing wall. Finally, we provided a tube as a shortcut through the high wall. In the equal-height arena, most frogs chose to escape via the quadrant facing their former calling site. However, when challenged with different heights, nearly all frogs chose the low wall, directing their movements away from the calling site. In the "escape tunnel" experiment most frogs still chose the low wall. Our results show that displaced A. femoralis males can flexibly adjust their homing path and avoid (presumably energetically costly) obstacles, providing experimental evidence of spatial cognitive flexibility in an amphibian. PMID- 26997104 TI - Neural Univariate Activity and Multivariate Pattern in the Posterior Superior Temporal Sulcus Differentially Encode Facial Expression and Identity. AB - Faces contain a variety of information such as one's identity and expression. One prevailing model suggests a functional division of labor in processing faces that different aspects of facial information are processed in anatomically separated and functionally encapsulated brain regions. Here, we demonstrate that facial identity and expression can be processed in the same region, yet with different neural coding strategies. To this end, we employed functional magnetic resonance imaging to examine two types of coding schemes, namely univariate activity and multivariate pattern, in the posterior superior temporal cortex (pSTS) - a face selective region that is traditionally viewed as being specialized for processing facial expression. With the individual difference approach, we found that participants with higher overall face selectivity in the right pSTS were better at differentiating facial expressions measured outside of the scanner. In contrast, individuals whose spatial pattern for faces in the right pSTS was less similar to that for objects were more accurate in identifying previously presented faces. The double dissociation of behavioral relevance between overall neural activity and spatial neural pattern suggests that the functional-division of-labor model on face processing is over-simplified, and that coding strategies shall be incorporated in a revised model. PMID- 26997107 TI - Loss of CD38 Expression in Relapsed Refractory Multiple Myeloma. PMID- 26997106 TI - Rapamycin increases grip strength and attenuates age-related decline in maximal running distance in old low capacity runner rats. AB - Rapamycin is known to extend lifespan. We conducted a randomized placebo controlled study of enteric rapamycin-treatment to evaluate its effect on physical function in old low capacity runner (LCR) rats, a rat model selected from diverse genetic background for low intrinsic aerobic exercise capacity without genomic manipulation and characterized by increased complex disease risks and aging phenotypes. The study was performed in 12 male and 16 female LCR rats aged 16-22 months at baseline. The treatment group was fed with rapamycin containing diet pellets at approximately 2.24mg/kg body weight per day and the placebo group with the same diet without rapamycin for six months. Observation was extended for additional 2 months. Physical function measurements include grip strength measured as maximum tensile force using a rat grip strength meter and maximum running distance (MRD) using rat physical treadmill test. The results showed that rapamycin improved grip strength by 13% (p=.036) and 60% (p=.001) from its baseline in female and male rats, respectively. Rapamycin attenuated MRD decline by 66% (p=.001) and 46% (p=.319) in females and males, respectively. These findings provide initial evidence for beneficial effect of rapamycin on physical functioning in an aging rat model of high disease risks with significant implication in humans. PMID- 26997108 TI - miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells. AB - BACKGROUND: In the moderate and end stages of intervertebral disc (IVD) degeneration, endochondral ossifications are found in the IVD. PURPOSE: The aim of this study was to investigate whether endochondral ossification in the late stages of disc degeneration is due to the differentiation of resident progenitor cell in the annulus fibrosus (AF) and the potential signaling pathways in vitro. STUDY DESIGN: This is an in vitro study of AF cell osteogenic differentiation and possible mechanisms METHODS: Normal annulus fibrosus (NAF) and degenerated annulus fibrosus (DAF) cells were isolated from tissue removed surgically from juvenile patients with idiopathic scoliosis and adult patients with degenerative scoliosis. Osteogenic differentiation was investigated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and histology. The effects of miR-221 on osteogenesis were measured by overexpression of miR-221 with lentivirus. BMP2 and phospho-Smad proteins were detected by Western blotting. RESULTS: Both NAF and DAF cells underwent osteogenic differentiation, which was confirmed by detecting mineralization of the cell cultures and by an increase in the expression mRNAs for BMP2, runx2, alkaline phosphatase (ALP), and osteocalcin. DAF cells exhibited increased osteogenic differentiation potential over the NAF cells. By contrast to the elevated phospho-Smads, the basal level of miR-221 significantly decreased in DAF cells compared with that in NAF cells. Cultures of both cell types in osteogenic medium showed a decrease in miR-221 expression, and overexpression of miR-221 markedly decreased the level of BMP2, phospho-Smads, and the expression of osteogenic genes in DAF cells. The osteogenic potential of DAF cells diminished by the overexpression of miR-221. CONCLUSION: Compared with NAF cells, AF cells from degenerated discs have a greater tendency for osteogenic differentiation, which involves the BMP-Smad pathways and can be regulated by miR-221. These observations may be developed into a therapeutic to prevent the endochondral ossification. PMID- 26997109 TI - Extensive bone remodeling from a solitary fibrous tumor of the cervical spine. PMID- 26997111 TI - Multiple myeloma presenting with acute bony spinal cord compression and mechanical instability successfully managed nonoperatively. AB - BACKGROUND CONTEXT: Multiple myeloma (MM) with spinal involvement may present with spinal cord or cauda equina compression, with or without neurological impairment. This occurs when a soft-tissue myelomatous mass extends into the epidural space (Barron et al., 1959 [1]). The mainstay of management for such lesions in patients with normal neurology is chemotherapy and radiotherapy or radiotherapy alone, but those with neurological compromise require surgical decompression with adjuvant therapy (Patchell et al., 2005 [2]). Infrequently, patients with MM present with spinal cord compression and neurological impairment due to bony encroachment from vertebral translation and kyphosis where significant lytic bone disease has rendered the spine mechanically unstable. The standard management for these patients is surgical decompression and internal fixation. PURPOSE: This study aimed to report a high-risk myeloma patient with a mechanically unstable spine, acute spinal cord compression, and neurologic deficit that was treated successfully using nonoperative means. STUDY DESIGN: Case report. METHODS: A 37-year-old male patient with MM was referred to our tertiary referral spinal unit with acute bony spinal cord compression and neurological impairment. Computer tomography revealed lytic lesions of T2 and T3 and anterolisthesis of T1 on T2 producing mechanical instability and magnetic resonance imaging confirmed extension of disease into the epidural space and cord compression. This was successfully managed with nonoperative treatment using a brace. RESULTS: Management in a brace restored clinical and radiological stability and normal neurological function. CONCLUSION: Certain high-risk myeloma patients with a mechanically unstable spine, acute spinal cord compression and neurologic deficit can be treated effectively in an appropriate brace when managed by a tertiary referral spinal unit. PMID- 26997110 TI - Reliability of the revised Scoliosis Research Society-22 and Oswestry Disability Index (ODI) questionnaires in adult spinal deformity when administered by telephone. AB - BACKGROUND CONTEXT: The non-response rates are as high as 20% to 50% after 5 years of follow-up in adult spinal deformity (ASD) surgery. Minimizing loss to follow-up is essential to protect the quality of data in long-term studies. Phone and internet administration of outcomes instruments has grown in popularity and has been found to not only provide a convenient way of collecting data, but also show improved response rates. PURPOSE: The study aimed to examine the reliability of the revised Scoliosis Research Society-22 (SRS-22r) and the Oswestry Disability Index (ODI) questionnaires in ASD patients when administered by telephone. STUDY DESIGN/SETTING: This is a single-center, randomized crossover phone validation of ASD patients. PATIENT SAMPLE: The study included ASD patients presenting to a tertiary spine care center. OUTCOME MEASURES: The outcome measures were ODI and SRS-22r. METHODS: Forty-nine patients (mean age: 55.7 years) with ASD were randomized in a 1:1 ratio to either phone completion of the SRS-22r and ODI followed by in-office completion, or to in-office completion followed by phone completion. An interval of 2 to 4 weeks was placed between administrations of each version. A paired t test was used to assess the difference between the written and phone versions, and intraclass correlation coefficients were used to assess homogeneity. Finally, goodness-of-fit testing was used to assess version preference. RESULTS: There was no significant difference between the phone and in-office versions of the SRS-22r (p=.174) or the ODI (p=.320). The intraclass correlation coefficients of the SRS-22r and ODI were 0.91 and 0.86, respectively. Completion over the phone was the most popular option (57% preferred phone, 29% preferred in-office, and 14% had no preference). CONCLUSIONS: Phone administration of the SRS-22r and ODI to ASD patients provides a convenient and reliable tool for reducing loss of follow-up data. PMID- 26997112 TI - Ventral cervicothoracic epidural hematoma during anticoagulant therapy and rapid spontaneous resolution. PMID- 26997113 TI - Erratum to: "Discussion of "Combining Health Data Uses to Ignite Health System Learning'". PMID- 26997115 TI - Bidirectional Interaction of Alanine with Sulfuric Acid in the Presence of Water and the Atmospheric Implication. AB - Amino acids are recognized as important components of atmospheric aerosols, which impact on the Earth's climate directly and indirectly. However, much remains unknown about the initial events of nucleation. In this work, the interaction of alanine [NH2CH(CH3)COOH or Ala], one of the most abundant amino acids in the atmosphere, with sulfuric acid (SA) and water (W) has been investigated at the M06-2X/6-311++G(3df, 3pd) level of theory. We have studied thermodynamics of the hydrated (Ala)(SA) core system with up to four water molecules. We found that Ala, with one amino group and one carboxyl group, can interact with H2SO4 and H2O in two directions and that it has a high cluster stabilizing effect similar to that of ammonia, which is one of the key nucleation precursor. The corresponding Gibbs free energies of the (Ala)(SA)(W)n (n = 0-4) clusters formation at 298.15 K predicted that Ala can contribute to the stabilization of small binary clusters. Our results showed that the hydrate distribution is temperature-dependent and that a higher humidity and temperature can contribute to the formation of hydrated clusters. PMID- 26997114 TI - Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation. AB - Accumulation of methylglyoxal (MG) contributes to glucotoxicity and mediates beta cell apoptosis. The molecular mechanism by which GLP-1 protects MG-induced beta cell apoptosis remains unclear. Metformin is a first-line drug for treating type 2 diabetes associated with AMPK activation. However, whether metformin prevents MG-induced beta cell apoptosis is controversial. Here, we explored the signaling pathway involved in the anti-apoptotic effect of GLP-1, and investigated whether metformin had an anti-apoptotic effect on beta cells. MG treatment induced apoptosis of beta cells, impaired mitochondrial function, and prolonged activation of AMP-dependent protein kinase (AMPK). The MG-induced pro-apoptotic effects were abolished by an AMPK inhibitor. Pretreatment of GLP-1 reversed MG induced apoptosis, and mitochondrial dysfunction, and suppressed prolonged AMPK activation. Pretreatment of GLP-1 reversed AMPK activator 5-aminoimidazole-4 carboxamide riboside (AICAR)-induced apoptosis, and suppressed prolonged AMPK activation. However, metformin neither leads to beta cell apoptosis nor ameliorates MG-induced beta cell apoptosis. In parallel, GLP-1 also prevents MG induced beta cell apoptosis through PKA and PI3K-dependent pathway. In conclusion, these data indicates GLP-1 but not metformin protects MG-induced beta cell apoptosis through improving mitochondrial function, and alleviating the prolonged AMPK activation. Whether adding GLP-1 to metformin provides better beta cell survival and delays disease progression remains to be validated. PMID- 26997116 TI - Autism as a Disorder of Altered Global Functional and Structural Connectivity. PMID- 26997117 TI - The Genetics-Driven Revival in Neuropsychiatric Drug Development. PMID- 26997118 TI - Oxytocin Effects on Brain Functioning in Humans. PMID- 26997119 TI - Toward a Multimodal, Multiscale Understanding of White Matter Abnormalities in Autism Spectrum Disorder. PMID- 26997120 TI - Migration of a clip to the common bile duct after laparoscopic cholecystectomy. PMID- 26997121 TI - Circular mucosal anopexy: Experience and technical considerations. AB - INTRODUCTION: Circular mucosal anopexy (CMA) achieves a more comfortable postoperative period than resective techniques. But complications and recurrences are not infrequent. This study aims to evaluate of the efficacy of CMA in the treatment of hemorrhoids and rectal mucosal prolapse (RMP). METHOD: From 1999 to 2011, 613 patients underwent surgery for either hemorrhoids or RMP in our hospital. CMA was performed in 327 patients. Gender distribution was 196 male and 131 female. Hemorrhoidal grades were distributed as follows: 28 patients had RMP, 46 2nd grade, 146 3rd grade and 107 4th grade. Major ambulatory surgery (MAS) was performed in 79.9%. Recurrence of hemorrhoids was studied and groups of recurrence and no-recurrence were compared. Postoperative pain was evaluated by Visual Analogical Scale (VAS) as well as early complications. RESULTS: A total of 31 patients needed reoperation (5 RMP, 2 with 2nd grade, 17 with 3rd grade,/with 4th grade). No statistically significant differences were found between the non recurrent group and the recurrent group with regards to gender, surgical time or hemorrhoidal grade, but there were differences related to age. In the VAS, 81.3% of patients expressed a postoperative pain <= 2 at the first week. Five patients needed reoperation for early postoperative bleeding. Six patients needed admission for postoperative pain. CONCLUSIONS: Recurrence rate is higher in CMA than in resective techniques. CMA is a useful technique for the treatment of hemorrhoids in MAS. Pain and the rate of complications are both low. PMID- 26997122 TI - A Photonic Crystal Laser from Solution Based Organo-Lead Iodide Perovskite Thin Films. AB - Perovskite semiconductors are actively investigated for high performance solar cells. Their large optical absorption coefficient and facile solution-based, low temperature synthesis of thin films make perovskites also a candidate for light emitting devices across the visible and near-infrared. Specific to their potential as optical gain medium for lasers, early work has demonstrated amplified spontaneous emission and lasing at attractively low thresholds of photoexcitation. Here, we take an important step toward practically usable perovskite lasers where a solution-processed thin film is embedded within a two dimensional photonic crystal resonator. We demonstrate high degree of temporally and spatially coherent lasing whereby well-defined directional emission is achieved near 788 nm wavelength at optical pumping energy density threshold of 68.5 +/- 3.0 MUJ/cm(2). The measured power conversion efficiency and differential quantum efficiency of the perovskite photonic crystal laser are 13.8 +/- 0.8% and 35.8 +/- 5.4%, respectively. Importantly, our approach enables scalability of the thin film lasers to a two-dimensional multielement pixelated array of microlasers which we demonstrate as a proof-of-concept for possible projection display applications. PMID- 26997123 TI - Use of outcome measurement by paediatric AHPs in Northern Ireland. AB - BACKGROUND: Professional standards advocate routine use of outcome measurement (OM) in the practice of allied health professionals (AHPs). Historically, OM has focused on impairment and its immediate constraints on activity, while current policy encourages the development and addition of impact-based OM. There appears to be an assumption at this stage of AHP development that the use of OM is well embedded into practice. However, there is no evidence to support this assumption, which leads to the current investigation into the overall readiness of paediatric AHPs-speech and language therapists (SLTs), occupational therapists (OTs) and physiotherapists (PTs)-to use OM. AIMS: To investigate the readiness of paediatric AHPs in the use of OM and to consider what influences this use. METHODS & PROCEDURES: A total of 133 paediatric AHPs working in the National Health Service (NHS) in Northern Ireland completed the Clinician Readiness for Measuring Outcomes Scale (CReMOS). CReMOS's 26 statements are rated on a six point Likert scale identifying readiness to use OM based on the Transtheoretical Model of Change. OUTCOMES & RESULTS: While about 75% of clinicians were using OM, 25% require support to roll this out in their practice. This pattern was similar across the professions, and while the majority perceived the value of OM, several factors influenced their use. CONCLUSIONS & IMPLICATIONS: Clinicians would benefit from protected time and support from experts/role models to promote and facilitate best practice in the use of OM. Furthermore, funding for AHP services based on measurable outcomes for service users would facilitate their use in practice. Further research teasing out the different types of OM and the supports and barriers to their use would be very valuable. PMID- 26997124 TI - Quasi-extinction risk and population targets for the Eastern, migratory population of monarch butterflies (Danaus plexippus). AB - The Eastern, migratory population of monarch butterflies (Danaus plexippus), an iconic North American insect, has declined by ~80% over the last decade. The monarch's multi-generational migration between overwintering grounds in central Mexico and the summer breeding grounds in the northern U.S. and southern Canada is celebrated in all three countries and creates shared management responsibilities across North America. Here we present a novel Bayesian multivariate auto-regressive state-space model to assess quasi-extinction risk and aid in the establishment of a target population size for monarch conservation planning. We find that, given a range of plausible quasi-extinction thresholds, the population has a substantial probability of quasi-extinction, from 11-57% over 20 years, although uncertainty in these estimates is large. Exceptionally high population stochasticity, declining numbers, and a small current population size act in concert to drive this risk. An approximately 5-fold increase of the monarch population size (relative to the winter of 2014-15) is necessary to halve the current risk of quasi-extinction across all thresholds considered. Conserving the monarch migration thus requires active management to reverse population declines, and the establishment of an ambitious target population size goal to buffer against future environmentally driven variability. PMID- 26997125 TI - Directional coalescence growth of ultralong Au93Pt7 alloy nanowires and their superior electrocatalytic performance in ethanol oxidation. AB - Ultralong (~25-30 MUm) surface-Pt-rich Au93Pt7 alloy nanowires (ANWs) were achieved by a directional coalescence between spherical nanoparticles. Also, the ANWs exhibit superior electrocatalytic activity and long-term durability towards ethanol oxidation, ~12 times in the mass activity better than the state-of-the art commercial Pt/C catalyst. PMID- 26997126 TI - Corrigendum: An interactive web-based application for Comprehensive Analysis of RNAi-screen Data. PMID- 26997127 TI - Aluminium and the human breast. AB - The human population is exposed to aluminium (Al) from diet, antacids and vaccine adjuvants, but frequent application of Al-based salts to the underarm as antiperspirant adds a high additional exposure directly to the local area of the human breast. Coincidentally the upper outer quadrant of the breast is where there is also a disproportionately high incidence of breast cysts and breast cancer. Al has been measured in human breast tissues/fluids at higher levels than in blood, and experimental evidence suggests that at physiologically relevant concentrations, Al can adversely impact on human breast epithelial cell biology. Gross cystic breast disease is the most common benign disorder of the breast and evidence is presented that Al may be a causative factor in formation of breast cysts. Evidence is also reviewed that Al can enable the development of multiple hallmarks associated with cancer in breast cells, in particular that it can cause genomic instability and inappropriate proliferation in human breast epithelial cells, and can increase migration and invasion of human breast cancer cells. In addition, Al is a metalloestrogen and oestrogen is a risk factor for breast cancer known to influence multiple hallmarks. The microenvironment is established as another determinant of breast cancer development and Al has been shown to cause adverse alterations to the breast microenvironment. If current usage patterns of Al-based antiperspirant salts contribute to causation of breast cysts and breast cancer, then reduction in exposure would offer a strategy for prevention, and regulatory review is now justified. PMID- 26997128 TI - Startle and blink reflex in high functioning autism. AB - An important clinical feature of autism is the presence of atypical responses to sensory stimuli. In this study, we investigated if high functioning autistic patients had abnormalities in the blink reflex and the startle reaction to auditory or somatosensory stimuli. Fourteen patients aged between 7 and 16 years were included in the study. We found a longer latency of the blink reflex, an increased duration and amplitude of the auditory startle reaction and a lower presence rate of the somatosensorial startle reaction in autistic patients. To better define the sensorial characteristics of the disease could improve the therapeutic management of children with autism spectrum disorder. PMID- 26997130 TI - Strong Exchange Coupling in a Trimetallic Radical-Bridged Cobalt(II) Hexaazatrinaphthylene Complex. AB - Reducing hexaazatrinaphthylene (HAN) with potassium in the presence of 18-c-6 produces [{K(18-c-6)}HAN], which contains the S=1/2 radical [HAN](.-) . The [HAN](.-) radical can be transferred to the cobalt(II) amide [Co{N(SiMe3 )2 }2 ], forming [K(18-c-6)][(HAN){Co(N'')2 }3 ]; magnetic measurements on this compound reveal an S=4 spin system with strong cobalt-ligand antiferromagnetic exchange and J~-290 cm(-1) (-2 J formalism). In contrast, the Co(II) centres in the unreduced analogue [(HAN){Co(N'')2 }3 ] are weakly coupled (J~-4.4 cm(-1) ). The finding that [HAN](.-) can be synthesized as a stable salt and transferred to cobalt introduces potential new routes to magnetic materials based on strongly coupled, triangular HAN building blocks. PMID- 26997129 TI - Cancer stem cell molecular reprogramming of the Warburg effect in glioblastomas: a new target gleaned from an old concept. AB - Prior targeted treatment for glioblastoma multiforme (GBM) with anti-angiogenic agents, such as bevacizumab, has been met with limited success potentially owing to GBM tumor's ability to develop a hypoxia-induced escape mechanism--a glycolytic switch from oxidative phosphorylation to glycolysis, an old concept known as the Warburg effect. New studies points to a subpopulation of cells as a source for treatment-resistance, cancer stem cells (CSCs). Taken together, the induction of the Warburg effect leads to the promotion of CSC self-renewal and undifferentiation. In response to hypoxia, hypoxia-inducible transcription factor is upregulated and is the central driver in setting off the cascade of events in CSC metabolic reprogramming. Hypoxia-inducible transcription factor upregulates GLUT1 to increase glucose uptake into the cell, upregulates HK2 and PK during glycolysis, upregulates LDHA in the termination of glycolysis, and downregulates PDH to redirect energy production toward glycolysis. This review aims to unite these old and new concepts simultaneously and examine potential enzyme targets driven by hypoxia in the glycolytic phenotype of CSCs to reverse the metabolic shift induced by the Warburg effect. PMID- 26997131 TI - Stabilisation of infected peri-articular nonunions with an antibiotic impregnated cement coated locking plate: Technique and indications. PMID- 26997133 TI - ORIF with percutaneous cross pinning via the posterior approach for paediatric widely displaced supracondylar femoral fractures. AB - BACKGROUND: Supracondylar femoral fractures are considered uncommon in children; however, they are frequently associated with complications. To date, the optimal surgical approach for these fractures remains unclear. OBJECTIVE: The aim of the present study was to determine the outcomes of open reduction with percutaneous cross pinning via the posterior approach for paediatric widely displaced, pulseless supracondylar femoral fractures refractory to closed reduction. METHODS: Between March 2007 and March 2014, 18 patients (11 boys and seven girls; average age, 6.6 years; range, 3.5-8.5 years) with widely displaced, pulseless supracondylar femoral fractures underwent ORIF with crossed percutaneous Kirschner wires via the posterior approach. The K-wires and plaster or brace were removed and knee rehabilitation exercises initiated at 4-6 weeks after surgery, and the children resumed walking at 8-10 weeks. We evaluated surgical outcomes and post-operative knee function using the Knee Society Score (KSS) scale at 6 and 12 months after surgery. RESULTS: Anatomical reduction was achieved in all patients. The average follow-up duration was 37 months (range, 11-60 months). The average fracture healing duration was 4.6 weeks (range, was 4-5 weeks). No patient exhibited a valgus deformity of more than 5 degrees , nonunion, neurovascular injury and knee infection. On comparison with the contralateral limb, eight patients exhibited a ipsilateral limb length discrepancy of 1.0-2.0cm after a year. At 2 years, however, none of the patients (n=15) exhibited a discrepancy of more than 1cm. All patients showed normal function and imaging findings during the follow-up. The peak mean KSS was 95.11 at 6 months after surgery, which remained more or less constant at 12 months (95.23; n=17). CONCLUSIONS: Our results suggest that ORIF with percutaneous cross pinning via the posterior approach ensures anatomical reduction and excellent function and is a safe, straightforward and effective procedure for paediatric widely displaced, pulseless supracondylar femoral fractures. LEVEL OF EVIDENCE: Level III. PMID- 26997132 TI - Heterotopic Ossification following acetabular fixation: Incidence and risk factors: 10-year experience of a tertiary centre. AB - BACKGROUND: Heterotopic Ossification (HO) is a well-recognized complication following acetabular fracture fixation and its presence is prognostic for suboptimal clinical outcome. There are many controversies pertaining to its aetiology, including surgical approach, associated injuries and the use of HO prophylaxis. Long term data from high volume centres is necessary to address these issues. AIM: To determine the incidence of HO post open reduction and internal fixation (ORIF) of acetabular fractures and to examine the associated risk and prognostic factors. METHOD: We studied a cohort of 369 consecutive acetabular fractures that underwent ORIF at our institution over a 10 year period. Data was analyzed using univariate and multivariate logistic regression. RESULTS: The existence of HO was evident in 65 patients (17.62%), of these 39 (60.0%) were Class I, 16 (24.6%) were Class II, 8 (12.3%) were Class III, and 2 (3.1%) were Class IV according to Brooker Classification. We found a significant association between admission to an Intensive Care Unit (ICU) (P-value=0.039), chest injury (P-value=0.013), multiple fractures (P-value=0.005), and the time lapse between injury and operation (P-value=0.025), and some statistical significance with surgical approach, ipsilateral fractures, open fractures, tibial and patellar fractures. Age over 30 years as the only prognostic factor for severe HO. Prophylaxis with Indomethacin did not appear to confer any benefit in our patient group. CONCLUSION: The risk factors for developing HO following acetabular fracture fixation are multifactorial and include admission to ICU, associated chest injuries, multiple fractures and delay between injury and surgery. Surgical approach, ipsilateral fractures and tibia and patellar fractures may also play a role. Age over thirty years was the only prognostic factor for developing severe HO. PMID- 26997134 TI - Reliability of tristimulus colourimetry in the assessment of cutaneous bruise colour. AB - BACKGROUND: Bruising is one of the most common types of injury clinicians observe among victims of violence and other trauma patients. However, research has shown commonly used qualitative description of cutaneous bruise colour via the naked eye is subjective and unreliable. No published work has formally evaluated the reliability of tristimulus colourimetry as an alternative for assessing bruise colour, despite its clinical and research applications in accurately assessing skin colour. The purpose of this study was to systematically evaluate the test retest and inter-observer reliability of tristimulus colourimetry in the assessment of cutaneous bruise colour. METHODS: Two researchers obtained repeated tristimulus colourimetry measures of cutaneous bruises with participants of diverse skin colour. Measures were obtained using the Minolta CR-400 Chomameter. Commission Internationale d'Eclairage (CIE) L*a*b* colour space was used. Data was analysed using intraclass correlation coefficients (ICC), Cronbach's alpha, and minimal detectable change (MDC) on all three L*a*b* values. RESULTS: The colorimeter demonstrated excellent test-retest or intra-rater reliability (L* ICC=0.999; a* ICC=0.973; b* ICC=0.892) and inter-rater reliability (L* ICC=0.997; a* ICC=0.976; b* ICC=0.982). CONCLUSIONS: With consistent placement, the tristimulus colourimetry is reliable for the objective assessment and documentation of cutaneous bruise colour for purposes of clinical practice and research. Recommendations for use in practice/research are provided. PMID- 26997135 TI - Incorporating the concept of leadership in pharmacy curriculums of developing nations. PMID- 26997136 TI - How to best manage time interaction with patients? Community pharmacist workload and service provision analysis. AB - BACKGROUND: Primary health care disease management models are rooted in multidisciplinary participation; however, implementation of services is lagging behind desires and predictions. Barriers like workload and lack of demand have been described. The aim of this research is to observe the workload and work patterns of Portuguese community pharmacists, and relate it with the demand of pharmaceutical services. METHOD: A time-and-motion observational study was performed to describe community pharmacists' workload in a sample of four pharmacies in the metropolitan Lisbon area. A reference list of activities to be observed was developed by reviewing other studies of community pharmacy work. This study took place during a weekday's 8-h shift, focusing on pharmacists' activities. Data to be collected included the type and duration of the activity, who performed it and where. To estimate the demand of pharmaceutical care services, "thematic-patient scenarios" were developed. These scenarios were based on the defined daily dose and package size of the most consumed medicines in Portugal, combined with data obtained from the four pharmacies' information systems on the day the observational study took place. RESULTS: Between 67.0% and 81.8% of the registered activities were pharmacist-patient interactions. These interactions summed 158.44 min, with a mean duration of 3.98 min per interaction. On average, participant pharmacies' professionals handled 4.2 prescriptions and 0.9 over-the-counter (OTC) consultations per hour. About one third of the day was spent performing administrative and non-differentiated tasks. About 54.92 min were registered as free time, 50% of which were "micro pauses" with 1 min or less. The most dispensed therapeutic subgroup was antihypertensive drugs, while the dispensation of antidiabetics was characterized by a high number of packages sold per interaction. From the developed scenarios, one can estimate that a chronic patient may visit the pharmacy 4-9 times per year, depending on the condition presented. CONCLUSION: Workload results are very similar to findings from studies in other countries, which may be an indication of uniformity of community pharmacy practice across countries. The amount of time a pharmacist has at the counter to interact with a patient during a year renders disease management or therapeutic management non-viable. Also, the perception of "lack of time," many times reported as a barrier for service provision, must be called into question, since substantial available time was found. However, to turn this available time into usable time, redesign of work processes and new role definition are necessary. Both better management and new communication channels should be developed to address this gap and increase patient follow-up services. PMID- 26997137 TI - Detection of Bartonella spp. in Ixodes ricinus ticks and Bartonella seroprevalence in human populations. AB - Ticks are vectors for many bacterial, protozoan and viral pathogens and are potential vectors for Bartonella species. Hunters and foresters, therefore, may be regarded as high-risk groups for Bartonella infections. The aims of this study were (i) to identify Bartonella species in questing Ixodes ricinus ticks collected in all provinces of Austria, and (ii) to determine the prevalence of antibodies to Bartonella species in hunters and blood donors in eastern Austria. A total of 515 larval, nymphal and adult I. ricinus, collected throughout Austria in 2005, were selected from the tick library at the Institute for Hygiene and Applied Immunology of the Medical University of Vienna and screened in a specific real-time PCR that targeted a region of the ssrA gene of Bartonella species. The overall Bartonella infection rate was 2.1% (11/515) and the highest rate, 7.5% (4/53), was found in ticks from Vienna. This finding was confirmed by screening a further 60 I. ricinus collected from Vienna in 2013: of these, 6.7% (4/60) were positive for Bartonella spp. The rate of infection was always higher in adult ticks. Sequence analysis in the Bartonella-positive ticks identified several species, including B. henselae, B. doshiae and B. grahamii. To our knowledge this is the first time that these species have been identified in I. ricinus in Austria. Prevalence of IgG antibodies against B. henselae and B. quintana was determined in serum samples from hunters (100) and blood donors (100): in hunters 23% were positive for B. quintana and in 2 samples (2%), antibodies to both B. quintana and B. henselae were detected; in blood donors 22% were positive for B. quintana, 1% for B. henselae and 5% for both. These results indicate that exposure to ticks does not constitutes a relevant risk for Bartonella infection. PMID- 26997138 TI - No change in mRNA expression of immune-related genes in peripheral blood mononuclear cells challenged with Theileria annulata in Murrah buffalo (Bubalus bubalis). AB - Water buffaloes (Bubalus bubalis) act as carrier to Theileria annulata and show less clinical sign of tropical theileriosis as compared to indigenous and exotic cattle. Differential expression of immune-related genes such as major histocompatibility complex, class II, DQ alpha 1 (MHC-DQalpha), signal-regulatory protein alpha (SIRPA), prion protein (PRNP), Toll-like receptor 10 (TLR10), c musculoaponeurotic fibrosarcoma oncogene homolog (cMAF) and V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) genes influence host resistance to this disease in exotic, crossbred and indigenous cattle. In the present study we examined the differential mRNA expression of the abovesaid immune-related genes in response to T. annulata infection in buffaloes. Peripheral blood mononuclear cells (PBMCs) harvested from blood samples of buffaloes were challenged with ground-up tick supernatant carrying T. annulata sporozoites in vitro. After 48h of in vitro challenge qPCR was employed to measure the relative mRNA expression of MHC-DQalpha, SIRPA, PRNP, TLR10, cMAF and MAFB genes in infected and control PBMCs. In the current study, the selected genes showed no change in mRNA expression after T.annulata infection which indicates that they have little role in providing host resistance to theileriosis in buffaloes. PMID- 26997139 TI - Comparison of Assurance GDS((r)) MPX ID for Top STEC with Reference Culture Methods for the Detection of E. coli Top 6 STEC; Direct Confirmation of Top 6 STEC from Isolation Plates and Determination of Equivalence of PickPen((r)) and FSIS OctoMACSTM Concentration Protocols. AB - Assurance GDS((r)) MPX ID for Top Shiga toxin-producing Escherichia coli (STEC; MPX ID) was validated according to the AOAC INTERNATIONAL Methods Committee Guidelines for Validation of Microbiological Methods for Foods and Environmental Surfaces as (1) a secondary screening method for specific detection of the Top 6 STEC serogroups (O26, O45, O103, O111, O121, and O145) in raw beef trim, raw ground beef, raw spinach, and on stainless steel; and (2) as a confirmatory method for the identification of pure culture isolates as Top 6 STEC. MPX ID is used in conjunction with the upfront BCS Assurance GDS MPX Top 7 STEC assay. This Performance Tested Method(SM) validation has two main parts: Method Developer studies and the Independent Laboratory study. A total of 180 samples and controls were analyzed. Results showed that MPX ID had no statistically significant differences with the reference culture methods for the detection of Top 6 STEC in the food matrixes (raw beef trim, raw ground beef, and raw spinach) and environmental sponges (stainless steel) studied. Inclusivity/exclusivity studies were also conducted. One hundred percent inclusivity among the 50 Top 6 STEC serovars tested and 100% exclusivity for the 30 non-Top 6 STEC organisms tested were demonstrated. For validation of MPX ID as a confirmatory method for isolated colonies, all inclusivity and exclusivity organisms were streaked for isolation onto five STEC plating media: modified rainbow agar, Levine's eosin-methylene blue (L-EMB) agar, rainbow agar with novobiocin and cefixime, and enterohemolysin agar with selective agents as well as trypticase soy agar with yeast extract. These isolated colonies were suspended and analyzed by Assurance GDS MPX Top 7 STEC and MPX ID. MPX ID was able to correctly confirm all inclusivity organisms from all plate types, except two STEC isolates from L-EMB agar plates only in the Independent Laboratory study. All exclusivity organisms were correctly determined by MPX ID as non-Top 6 STEC from the STEC plating media. An additional but separate part of these studies was a comparison of immunomagnetic separation (IMS) efficiency using the Assurance GDS procedure with a PickPen((r)) device and the U.S. Department of Agriculture procedure using the OctoMACSTM Separator device for plating onto chromogenic agar. Results demonstrated the equivalence of the two IMS procedures for plate confirmation of Top 7 STEC. PMID- 26997140 TI - Significant Broadband Photocurrent Enhancement by Au-CZTS Core-Shell Nanostructured Photocathodes. AB - Copper zinc tin sulfide (CZTS) is a promising material for harvesting solar energy due to its abundance and non-toxicity. However, its poor performance hinders their wide application. In this paper gold (Au) nanoparticles are successfully incorporated into CZTS to form Au@CZTS core-shell nanostructures. The photocathode of Au@CZTS nanostructures exhibits enhanced optical absorption characteristics and improved incident photon-to-current efficiency (IPCE) performance. It is demonstrated that using this photocathode there is a significant increase of the power conversion efficiency (PCE) of a photoelectrochemical solar cell of 100% compared to using a CZTS without Au core. More importantly, the PCE of Au@CZTS photocathode improved by 15.8% compared to standard platinum (Pt) counter electrode. The increased efficiency is attributed to plasmon resonance energy transfer (PRET) between the Au nanoparticle core and the CZTS shell at wavelengths shorter than the localized surface plasmon resonance (LSPR) peak of the Au and the semiconductor bandgap. PMID- 26997141 TI - Genomic profiling of male breast cancer. PMID- 26997142 TI - Reduced intensity transplantation in follicular lymphoma. PMID- 26997143 TI - Multitarget pharmacological inhibition for renal cell carcinoma. PMID- 26997145 TI - The challenges for scientific publishing, 60 years on. AB - The most obvious difference in science publishing between 'then' and 'now' is the dramatic change in the communication of data and in their interpretation. The democratization of science via the Internet has brought not only benefits but also challenges to publishing including fraudulent behavior and plagiarism, data and statistics reporting standards, authorship confirmation and other issues which affect authors, readers, and publishers in different ways. The wide accessibility of data on a global scale permits acquisition and meta-analysis to mine for novel synergies, and has created a highly commercialized environment. As we illustrate here, identifying unacceptable practices leads to changes in the standards for data reporting. In the past decades, science publishing underwent dramatic changes in the communication of data and in their interpretation, in the increasing pressure and commercialization, and the democratization of science on a global scale via the Internet. This article reviews the benefits and challenges to publishing including fraudulent behavior and plagiarism, data and statistics reporting standards, authorship confirmation and other issues, with the aim to provide readers with practical examples and hands-on guidelines. As we illustrate here, identifying unacceptable practices leads to changes in the standards for data reporting. This article is part of the 60th Anniversary special issue. PMID- 26997144 TI - Risk assessment of human health from exposure to the discharged ballast water after full-scale electrolysis treatment. AB - The presence of disinfection by-products (DBPs) releasing from ballast water management systems (BWMS) can cause a possible adverse effects on humans. The objectives of this study were to compute the Derived No Effect Levels (DNELs) for different exposure scenarios and to compare these levels with the exposure levels from the measured DBPs in treated ballast water. The risk assessment showed that when using animal toxicity data, all the DNELs values were approximately 10(3) 10(12) times higher than the exposure levels of occupational and general public exposure scenarios, indicating the level of risk was low (risk characterization ratios (RCRs) < 1). However, when using human data, the RCRs were higher than 1 for dichlorobromomethane and trichloromethane, indicating that the risk of adverse effects on human were significant. This implies that there are apparent discrepancies between risk characterization from animal and human data, which may affect the overall results. We therefore recommend that when appropriate, human data should be used in risk assessment as much as possible, although human data are very limited. Moreover, more appropriate assessment factors can be considered to be employed in estimating the DNELs for human when the animal data is selected as the dose descriptors. PMID- 26997146 TI - Fertility preservation in BRCA mutation carriers. AB - According to enhanced long-term survival rates of these patients, interest in fertility preservation for young women facing gonadotoxic therapies is increasing. Women who carry a mutation in the BRCA1 or BRCA2 gene have a specifically increased lifetime risk of developing breast and tubo-ovarian cancer. Moreover, they are at high risk of undergoing premature infertility due to the medical interventions that are often performed in order to reduce cancer risk or treat an already existing malignancy. Fertility issues are relevant for healthy BRCA mutation carriers, whose family-planning decisions are often influenced by the need of prophylactic bilateral salpingo-oophorectomy at young age. In BRCA mutation carriers who have a breast cancer at young age, the oncostatic treatment is associated with a significant ovarian toxicity linked to chemotherapy as well as to the long lasting hormonotherapy and to the need of delaying pregnancy for several years. Prompt counselling about different fertility preservation options should be offered to all young girls and women at high risk of ovarian insufficiency and infertility. Validated techniques to preserve fertility include oocyte and embryo cryopreservation, while experimental techniques include ovarian suppression with GnRH-analogs during chemotherapy and ovarian tissue cryopreservation. The choice of the best strategy depends on age, type of chemotherapy, partner status, cancer type, time available for fertility preservation intervention and the risk of ovarian metastasis. All available options should be offered and can be performed alone or in combination. A crucial point is to avoid a significant delay to cancer treatment. PMID- 26997147 TI - Genetic analysis of a novel splice-site mutation in TMC8 reveals the in vivo importance of the transmembrane channel-like domain of TMC8. PMID- 26997148 TI - Craniofacial disorders associated with airway obstruction in the neonate. AB - In infants with craniofacial disorders, upper airway obstruction is one of the primary causes for morbidity and mortality in the neonatal period. Infants with craniofacial disorders, including Pierre Robin sequence, are at high risk for obstructive sleep apnea syndrome. Because of the complexity of their care, these neonates are usually followed by a multidisciplinary team to ensure timely evaluation and optimal treatment. In addition to history and physical examination, clinical evaluation may include genetic testing, imaging, endoscopy, and polysomnography. There are various treatment options, both surgical and non surgical, that may be used depending on clinical assessment, underlying condition, and severity of disease. Recent advances have led to better assessment and treatment of these patients, but many questions remain. This review outlines the available literature pertaining to the evaluation and management of upper airway obstruction in the neonate with craniofacial conditions, with a particular focus on Pierre Robin sequence. PMID- 26997150 TI - The Co-regulatory Role of 5-Lipoxygenase and Cyclooxygenase-2 in the Carcinogenesis and their Promotion by Cigarette Smoking in Colons. AB - The arachidonic acid metabolizing enzymes, cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX), are both highly expressed during the carcinogenesis in colons. Cigarette smoking promotes these carcinogenic processes at the early stage during adenoma formation. In this article, the involvement of COX-2 and 5 LOX, alongside with the dual COX/5-LOX inhibitors in colorectal cancer development is introduced. The co-regulation of 5-LOX and COX-2 in colon cancer growth and its relationship with cigarette smoke and hyaluronic acid-CD44v6 is also described. It is envisaged that dual inhibition of 5-LOX/COX could be the most promising therapeutic option for the treatment of colorectal cancer in humans. PMID- 26997149 TI - Probiotic supplementation does not improve eradication rate of Helicobacter pylori infection compared to placebo based on standard therapy: a meta-analysis. AB - This meta-analysis included eligible randomized controlled trials (RCTs) with the aim of determining whether probiotic supplementation can improve H. pylori eradication rates. PUBMED, EBSCO, Web of Science, and Ovid databases were searched. We included RCTs that investigated the effect of combining probiotics, with or without a placebo, with standard therapy. A total of 21 RCTs that reported standard therapy plus probiotics were included. Compared to the placebo group, the probiotics group was 1.21(OR 1.21, 95% CI: 0.86, 1.69) and 1.28 (OR 1.28, 95% CI: 0.88, 1.86) times more likely to achieve eradication of H. pylori infection in intent-to-treat (ITT) analysis and per protocol (PP) analysis, respectively. Probiotics with triple therapy plus a 14-day course of treatment did not improve the eradication of H. pylori infection (OR 1.44, 95% CI: 0.87, 2.39) compared to the placebo. Moreover, the placebo plus standard therapy did not improve eradication rates compared to standard therapy alone (P = 0.816). However, probiotics did improve the adverse effects of diarrhea and nausea. These pooled data suggest that the use of probiotics plus standard therapy does not improve the eradication rate of H. pylori infection compared to the placebo. PMID- 26997151 TI - Computer Aided Drug Design Approaches for Identification of Novel Autotaxin (ATX) Inhibitors. AB - Autotaxin (ATX) has become an attractive target with a huge pharmacological and pharmacochemical interest in LPA-related diseases and to date many small organic molecules have been explored as potential ATX inhibitors. As a useful aid in the various efforts of identifying novel effective ATX inhibitors, in silico methods can serve as an important and valuable tool. Especially, Virtual Screening (VS) has recently received increased attention due to the large datasets made available, the development of advanced VS techniques and the encouraging fact that VS has contributed to the discovery of several compounds that have either reached the market or entered clinical trials. Different techniques and workflows have been reported in literature with the goal to prioritize possible potent hits. In this review article several deployed virtual screening strategies for the identification of novel potent ATX inhibitors are described. PMID- 26997152 TI - Imaging Agents in Targeting Tumor Hypoxia. AB - Tissue hypoxia may occur in many diseases, specifically during the occurrence and growth of malignant solid-tumors. Targeting hypoxia is one of the most significant characteristics of tumors in diagnosis, monitoring, and treatment. This review summarizes the current oxygen-sensitive imaging agents used to target tumor hypoxia, including positron-emission computed tomography/single photon emission computed tomography radionuclide labeled tracers, magnetic resonance imaging contrast agents for hypoxia detection, and hypoxia-sensitive optical imaging probes. Researchers have utilized nanotechnology as a useful toolkit to improve the effects of oxygen-sensitive imaging agents. We emphasize the progress and influence of nanotechnology in these materials and technologies. This review demonstrates that hypoxia imaging agents have promising prospects, and may provide helpful information for tumor diagnosis and prognosis. PMID- 26997153 TI - Anti-Psoriasis Agents from Natural Plant Sources. AB - Psoriasis is a chronic inflammatory immune-mediated skin disease. It affects most races, does not have any sexual predilections and can manifest at any age of life. Psoriasis is more frequent in certain racial groups and geographical areas. For these reasons, both genetic and environmental factors could be considered. In this review, we discuss promising natural compounds, their molecular targets and mechanisms, which may help the further design of new anti-psoriasis agents. Literature documents the widespread use of herbal remedies worldwide, and the presence of some phytochemicals supports the efficacy of some botanical treatments. The research on natural products has greatly contributed to the progress in the treatment of skin diseases such as psoriasis and many of these compounds are now being used. Understanding the mechanism of these molecules will contribute to the development of more specific preventive strategies for the treatment of psoriasis. PMID- 26997155 TI - Models of visual categorization. AB - Visual categorization refers to our ability to organize objects and visual scenes into discrete categories. It is an essential skill as it allows us to distinguish friend from foe or edible versus poisonous food. Understanding how the visual system categorizes objects and scenes is a challenge because it requires bridging the gap between different levels of understanding-from the level of neural circuits and neural networks to the level of information processing and, ultimately, behavior. Computational models have become powerful tools for integrating knowledge across these levels of analysis. We review recent progress in our understanding of the computational mechanisms underlying visual categorization and discuss some of the remaining challenges. PMID- 26997156 TI - Investigations on HONO formation from photolysis of adsorbed HNO3 on quartz glass surfaces. AB - During the last few decades, nitrous acid (HONO) has attracted significant attention as a major source of the OH radical, the detergent of the atmosphere. However, the different daytime sources identified in the laboratory are still the subject of controversial discussion. In the present study, one of these postulated HONO sources, the heterogeneous photolysis of nitric acid (HNO3), was studied on quartz glass surfaces in a photo flow-reactor under atmospherically relevant conditions. In contrast to other investigations, a very low HNO3 photolysis frequency for HONO formation of J(HNO3-> HONO) = 2.4 * 10(-7) s(-1) (0 degrees SZA, 50% r.h.) was determined. If these results can be translated to atmospheric surfaces, HNO3 photolysis cannot explain the significant HONO levels in the daytime atmosphere. In addition, it is demonstrated that even the small measured yields of HONO did not result from the direct photolysis of HNO3 but rather from the consecutive heterogeneous conversion of the primary photolysis product NO2 on the humid surfaces. The secondary NO2 conversion was not photo enhanced on pure quartz glass surfaces in good agreement with former studies. A photolysis frequency for the primary reaction product NO2 of J(HNO3-> NO2) = 1.1 * 10(-6) s(-1) has been calculated (0 degrees SZA, 50% r.h.), which indicates that renoxification by photolysis of adsorbed HNO3 on non-reactive surfaces is also a minor process in the atmosphere. PMID- 26997154 TI - Why Antidiabetic Vanadium Complexes are Not in the Pipeline of "Big Pharma" Drug Research? A Critical Review. AB - Public academic research sites, private institutions as well as small companies have made substantial contributions to the ongoing development of antidiabetic vanadium compounds. But why is this endeavor not echoed by the globally operating pharmaceutical companies, also known as "Big Pharma"? Intriguingly, today's clinical practice is in great need to improve or replace insulin treatment against Diabetes Mellitus (DM). Insulin is the mainstay therapeutically and economically. So, why do those companies develop potential antidiabetic drug candidates without vanadium (vanadium- free)? We gathered information about physicochemical and pharmacological properties of known vanadium-containing antidiabetic compounds from the specialized literature, and converted the data into explanations (arguments, the "pros and cons") about the underpinnings of antidiabetic vanadium. Some discoveries were embedded in chronological order while seminal reviews of the last decade about the Medicinal chemistry of vanadium and its history were also listed for further understanding. In particular, the concepts of so-called "noncomplexed or free" vanadium species (i.e. inorganic oxido-coordinated species) and "biogenic speciation" of antidiabetic vanadium complexes were found critical and subsequently documented in more details to answer the question. PMID- 26997157 TI - Knockdown of a laccase in Populus deltoides confers altered cell wall chemistry and increased sugar release. AB - Plant laccases are thought to function in the oxidation of monolignols which leads to higher order lignin formation. Only a hand-full of laccases in plants have been functionally evaluated, and as such little is known about the breadth of their impact on cell wall chemistry or structure. Here, we describe a previously uncharacterized laccase from Populus, encoded by locus Potri.008G064000, whose reduced expression resulted in transgenic Populus trees with changes in syringyl/guaiacyl ratios as well as altered sugar release phenotypes. These phenotypes are consistent with plant biomass exhibiting reduced recalcitrance. Interestingly, the transgene effect on recalcitrance is dependent on a mild pretreatment prior to chemical extraction of sugars. Metabolite profiling suggests the transgene modulates phenolics that are associated with the cell wall structure. We propose that this particular laccase has a range of functions related to oxidation of phenolics and conjugation of flavonoids that interact with lignin in the cell wall. PMID- 26997158 TI - Phase unwrapping with graph cuts optimization and dual decomposition acceleration for 3D high-resolution MRI data. AB - PURPOSE: Existence of low SNR regions and rapid-phase variations pose challenges to spatial phase unwrapping algorithms. Global optimization-based phase unwrapping methods are widely used, but are significantly slower than greedy methods. In this paper, dual decomposition acceleration is introduced to speed up a three-dimensional graph cut-based phase unwrapping algorithm. METHODS: The phase unwrapping problem is formulated as a global discrete energy minimization problem, whereas the technique of dual decomposition is used to increase the computational efficiency by splitting the full problem into overlapping subproblems and enforcing the congruence of overlapping variables. Using three dimensional (3D) multiecho gradient echo images from an agarose phantom and five brain hemorrhage patients, we compared this proposed method with an unaccelerated graph cut-based method. RESULTS: Experimental results show up to 18-fold acceleration in computation time. CONCLUSIONS: Dual decomposition significantly improves the computational efficiency of 3D graph cut-based phase unwrapping algorithms. Magn Reson Med 77:1353-1358, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26997159 TI - [Comprehensive geriatric assessment (CGA) in elderly with cancer: For whom?]. AB - Scientific societies recommend the implementation of a comprehensive geriatric assessment (CGA) in cancer patients aged 70 and older. The EGA is an interdisciplinary multidimensional diagnostic process seeking to assess the frail older person in order to develop a coordinated plan of treatment and long-term follow-up. Identification of comorbidities and age-induced physiological changes that may increase the risk of anticancer treatment toxicities is essential to better assess the risk-benefit ratio in elderly cancer patients. The systematic implementation of a CGA for each patient is difficult to perform in daily practice. Therefore, it is recommended to screen vulnerable patients who will benefit from a complete CGA. Our work presents the vulnerability screening tools validated by at least two independent studies in a cancer elderly population setting. Among seven screening tools, the G8 and the VES13 are the most effective, and have been validated specifically in older population with cancer. The G8 is recommended by scientific societies and the French National Cancer Institute (INCa) because of its easy implementation in daily clinical practice, its high sensitivity and fair specificity. Although studies are underway to improve its performance, the G8 is currently the simplest tool to routinely identify older cancer patients who should have a complete assessment in geriatric oncology. PMID- 26997160 TI - [Headaches of unusual cause]. PMID- 26997161 TI - Studies on influence of polymer modifiers for fluorescent nanocrystals' cytotoxicity. AB - The presented studies aimed at investigation of the effect of CdSeS/ZnS quantum dots (QDs) stabilized with hyperbranched polyglycidol and its carboxylated derivative on adenocarcinomic human alveolar basal epithelial cells (A549). The first stage of studies concerned the modification of quantum dots with both types of the tested polymers with the use of pyridine as an intermediate agent. Subsequently, cytotoxic effect of the prepared nanoparticles was examined after various incubation time using MTT test (cell metabolic activity assay). Our studies revealed that CdSeS/ZnS with a diameter of 6nm, which were stabilized with hyperbranched polymers do not penetrate into cells, even after prolonged incubation time. Moreover, the cytotoxic effect of the tested QDs was observed over a range of tested concentrations (5-90MUM of Cd(2+)). It was confirmed that tested nanoparticles had significant influence on cell culture viability. The examined cytotoxic effect of the tested quantum dots was dependent on the type of polymer applied and the experiments indicated, that the one bearing carboxylic moieties is more toxic to A549 cells. PMID- 26997162 TI - Evaluation of nanoencapsulated verteporfin's cytotoxicity using a microfluidic system. AB - A new-generation of nanoencapsulated photosensitizers could be a good solution to perform effective photodynamic therapy (PDT). In this paper, we present physicochemical characterization and cellular investigation of newly prepared long-sustained release oil-core polyelectrolyte nanocarriers loaded with verteporfin (nano VP) in relation to free VP. For this purpose, a macroscale multiwell plates and multifunctional microfluidic system (for three types of cell cultures: monoculture, coculture and mixed culture) were used. A physical analysis of nano VP showed its high stability, monodispersity with unimodal shape and highly positive charge, what made them good candidates for cancer treatment. Biological properties (cellular internalization and uptake as well as cytotoxicity) of nano and free VP were evaluated using both carcinoma (A549) and normal (MRC-5) human lung cells. It was investigated that verteporfin was accumulated in cancer cells preferentially. Low cytotoxicity of the tested photosensitizer was observed in both macro, and microscale. However, in experiments performed in the microsystem, nano VP allowed the reduction of cytotoxic effect, especially in relation to the normal cells. It could result from the specific environment of cell growth in the microsystem which can quite closely mimic the in vivo conditions. Our results suggest that the presented microsystem could be a very useful microtool for testing of new generation of photosensitizers in various configurations of cell cultures, which are difficult to perform in the macroscale. Moreover, the prepared nano VP could be successfully used for further research i.e. evaluation of PDT procedures. PMID- 26997164 TI - Hypoxia enhances angiogenesis in an adipose-derived stromal cell/endothelial cell co-culture 3D gel model. AB - OBJECTIVES: This study aimed to investigate the influence of hypoxia on angiogenesis in a 3D gel, with co-culturing adipose-derived stromal cells (ASCs) and endothelial cells (ECs). MATERIALS AND METHODS: ASCs from green fluorescent protein-labeled mice and ECs from red fluorescent protein-labeled mice were co cultured in 3D collagen gels at 1:1 ratio, in normal and hypoxic oxygen conditions, and morphology of angiogenesis was observed using confocal laser scanning microscopy. To discover changes in growth factors between monoculture ASCs and ECs, transwell co-cultures of ASCs and ECs were applied. Semi quantitative PCR was performed to explore mRNA expression of growth factors. RESULTS: Enhanced angiogenesis was observed in 3D gels implanted with 1:1 mixture of ASCs and ECs after 7 days hypoxia. Genes including VEGFA/B, EGF-1, HIF-1a, IGF 1, PDGF, TGF-beta1 and BMP-2/4 in ECs, both monoculture and co-culture, were significantly enhanced after being cultured under hypoxia. In comparison, genes VEGFA/B, EGF-1, HIF-1a, TGF-beta1 and BMP-2 in ASCs increased. In all, factors VEGFA/B, EGF-1, HIF-1a, TGF-beta1 and BMP-2 increased in both ASCs and ECs after being cultured in hypoxia no matter whether as monoculture or co-culture. CONCLUSIONS: Co-culture of ASCs and ECs at 1:1 ratio in a 3D gel under hypoxia promoted angiogenesis. Those growth factors which were increased in both ASCs and ECs, indicate that VEGFA/B, EGF-1, HIF-1a, TGF-beta1 and BMP-2 might be responsible for enhancement in angiogenesis triggered by hypoxia. PMID- 26997163 TI - Robust Room-Temperature Quantum Spin Hall Effect in Methyl-functionalized InBi honeycomb film. AB - Two-dimensional (2D) group-III-V honeycomb films have attracted significant interest for their potential application in fields of quantum computing and nanoelectronics. Searching for 2D III-V films with high structural stability and large-gap are crucial for the realizations of dissipationless transport edge states using quantum spin Hall (QSH) effect. Based on first-principles calculations, we predict that the methyl-functionalized InBi monolayer (InBiCH3) has no dynamic instability, and hosts QSH state with a band gap as large as 0.29 eV, exhibiting an interesting electronic behavior viable for room-temperature applications. The topological characteristic is confirmed by s-pxy band inversion, topological invariant Z2 number, and the time-reversal symmetry protected helical edge states. Noticeably, the QSH states are tunable and robust against the mechanical strain, electric field and different levels of methyl coverages. We also find that InBiCH3 supported on h-BN substrate maintains a nontrivial QSH state, which harbors the edge states lying within the band gap of substrate. These findings demonstrate that the methyl-functionalized III-V films may be a good QSH platform for device design and fabrication in spintronics. PMID- 26997165 TI - Statins, regulatory T cells and diabetes. PMID- 26997166 TI - Children's Cognitive Functioning in Disasters and Terrorism. AB - A growing literature has begun to address the cognitions that influence children's disaster reactions as well as the effects of disasters on children's cognitions. These cognitions must be viewed in the context of developmental and cultural considerations as well as disaster-related factors such as exposure and secondary stressors. This review examines the extant literature on children's cognitions related to disasters and terrorism including threat appraisal, beliefs, attention and concentration, memory, academic achievement, and executive functioning. The review highlights areas where research is lacking such as the effect of disasters on children's attention, concentration, content of disaster memories, and executive functioning. It also notes findings that may advance post disaster screening and intervention. PMID- 26997168 TI - Soft tissue myoepithelial cell carcinoma. PMID- 26997167 TI - Essential medicines containing ethanol elevate blood acetaldehyde concentrations in neonates. AB - Neonates administered ethanol-containing medicines are potentially at risk of dose-dependent injury through exposure to ethanol and its metabolite, acetaldehyde. Here, we determine blood ethanol and acetaldehyde concentrations in 49 preterm infants (median birth weight = 1190 g) dosed with iron or furosemide, medicines that contain different amounts of ethanol, and in 11 control group infants (median birth weight = 1920 g) who were not on any medications. Median ethanol concentrations in neonates administered iron or furosemide were 0.33 (range = 0-4.92) mg/L, 0.39 (range = 0-72.77) mg/L and in control group infants were 0.15 (range = 0.03-5.4) mg/L. Median acetaldehyde concentrations in neonates administered iron or furosemide were 0.16 (range = 0-8.89) mg/L, 0.21 (range = 0 2.43) mg/L and in control group infants were 0.01 (range = 0-0.14) mg/L. There was no discernible relationship between blood ethanol or acetaldehyde concentrations and time after medication dose. CONCLUSION: Although infants dosed with iron or furosemide had low blood ethanol concentrations, blood acetaldehyde concentrations were consistent with moderate alcohol exposure. The data suggest the need to account for the effects of acetaldehyde in the benefit-risk analysis of administering ethanol-containing medicines to neonates. WHAT IS KNOWN: * Neonates are commonly treated with ethanol-containing medicines, such as iron and furosemide. * However, there is no data on whether this leads to appreciable increases in blood concentrations of ethanol or its metabolite, acetaldehyde. What is New: * In this study, we find low blood ethanol concentrations in neonates administered iron and/or furosemide but markedly elevated blood acetaldehyde concentrations in some infants receiving these medicines. * Our data suggest that ethanol in drugs may cause elevation of blood acetaldehyde, a potentially toxic metabolite. PMID- 26997169 TI - Lipoprotein composition in patients with type 1 diabetes mellitus: Impact of lipases and adipokines. AB - OBJECTIVE: High cardiovascular mortality in patients with type 1 diabetes (T1DM) is widely recognized. Paradoxically, these patients have been shown to have elevated HDL-C and reduced apoB-containing lipoproteins. The purpose of this investigation was to further characterize the lipoprotein composition in T1DM and to assess the role that lipases and adipokines may play in these differences. METHODS: T1DM patients (89) attending the Diabetes Clinic at the University of Miami and 42 healthy controls were recruited. Clinical characteristics, lipoprotein composition (by ultracentrifugation and HPLC), leptin, and adiponectin were measured in the full cohort, while a subgroup had LPL and hepatic lipase measured. RESULTS: Subjects were predominately Caucasian and Hispanic. HgbA1c's were above goal while their mean duration of diabetes was >20 years. LPL was 2-fold elevated in diabetic women versus controls (+107%{p=0.001}) with no difference in men. Hepatic lipase was reduced 50% {p<0.001} in women but increased 50% {p=0.079} in men. Leptin was similar to controls in women but reduced in men (-60%{p<0.001}). Adiponectin was elevated in both genders (men: +55%{p=0.018}; women: +46%{p=0.007}). LDL-C was reduced in both diabetic men ( 33%{p<0.001}) and women (-24%{p<0.001}) while HDL-C trended higher only in men (+13%{p=0.064}). Both total apoB (men: -31%{p<0.001}; women: -17%{p=0.016}) and triglycerides (men: -49%{p<0.001}; women: -31%{p=0.011}) were reduced in both genders while total apoA-I was increased in both (men: +31%{p<0.001}; women: +19%{p=0.008}). Both men and women had increases in LpA-I (+66%{p<0.001}; +40%{p=0.001}) which accounted for essentially the entire increase in HDL mass. VLDL lipids (men: -53->70%; women: -31->57%) were lower as was apoB (particle number) in men (-51{p<0.001}) with a similar trend in women (-35%{p=0.066}). Cholesterol esters in the particle core were depleted in both genders relative to both apoB (men: -41%; women: -37%) and triglycerides (men: -38%; women: -34%) (all{p<0.009}). There were similar differences in IDL. HDL-L lipids (except triglycerides) (men: +45->74%; women: +49->77%{p<0.006}), apoA-1 (men: +162%; women: +117%{p<0.001}), and apoA-II (men: +64%{p=0.008}; women: +55%{p=0.014}) were higher in T1DM patients. These differences produced dramatic increases in LpA-I (men: +221%; women +139%{p<0.001}) and total HDL-L mass (men: +85%; women: +78%{p<0.001}). ApoM (men: +190%; women: +149%{p<0.001}) was also dramatically increased. Conversely, HDL-D lipids were lower in both genders (-20%->50%) while apoA-I was not different in either. ApoA-II was lower only in the diabetic women (-25%{p=0.015}). LPL activity correlated primarily with IDL(-), LDL(-), HDL-L(+), and HDL-D(-) only in the women. HL correlated weakly with VLDL(+), LDL(+), HDL-L( ), and HDL-D(+) in women but had much stronger correlations with VLDL(-), IDL(-), and HDL-L(+). Adiponectin correlated with VLDL(-), IDL(-), LDL(-), HDL-L(+), and HDL-D(-) in women but only HDL-L(+) and HDL-D(-) in men. Leptin correlated with very few parameters in women but did correlate weakly with several HDL-L(-) and HDL-M(-) parameters. CONCLUSION: Lipoprotein composition and adipokine concentrations in both genders as well as lipase activities in the women would be expected to reduce the atherosclerotic risk in these patients with T1DM. These data suggest that there are functional lipoprotein abnormalities responsible for their CV risk that are not reflected in their plasma concentrations. PMID- 26997170 TI - Maximum BMI and microvascular complications in a cohort of Japanese patients with type 2 diabetes: the Japan Diabetes Complications Study. AB - AIMS: The aim of this study was to examine the associations between possible indices of obesity based on information on weight history and the incidence of microvascular complications. METHODS: A cohort of individuals with type 2 diabetes from 59 institutes in Japan was followed for 8years. Patients were classified into three categories according to weight at entrance and past maximum weight: normal (BMI at baseline <25kg/m(2) and maximum BMI <25kg/m(2)), past obesity (BMI at baseline <25kg/m(2) and maximum BMI >=25kg/m(2)), and current obesity (BMI at baseline >=25kg/m(2)) groups. The outcomes were diabetic retinopathy and overt nephropathy. RESULTS: BMI at maximum and baseline of the 1809 patients was 26.5+/-3.5 and 23.1+/-3.0kg/m(2) (p<0.01), respectively (23.0+/ 1.6 and 20.6+/-1.9kg/m(2) for normal, 27.4+/-2.0 and 22.8+/-1.4kg/m(2) for past obesity, and 30.1+/-2.9 and 27.0+/-1.8kg/m(2) for current obesity). The hazard ratios of past and current obesity compared to normal were 1.92 (95% CI, 1.08 3.41; p=0.03) and 2.21 (1.16-4.22; p=0.02), respectively, for overt nephropathy and 1.38 (1.05-1.83; p=0.02) and 1.64 (1.18-2.28; p<0.01), respectively, for diabetic retinopathy after adjustment for confounders. CONCLUSIONS: Past obesity as well as current obesity were associated with increased risks of microvascular complications. Further identification of high-risk populations may be possible by classifying normal weight patients by past obesity. PMID- 26997171 TI - Simple equations for complex physiology: can we use VCO2 for calculating energy expenditure? PMID- 26997172 TI - Effect of oral polyamine supplementation pre-weaning on piglet growth and intestinal characteristics. AB - A high proportion of piglets fail to adapt to the changing composition of their diet at weaning, resulting in weight loss and increased susceptibility to pathogens. Polyamines are present in sow milk and promote neonatal maturation of the gut. We hypothesised that oral spermine and spermidine supplementation before weaning would increase piglet growth and promote gastrointestinal development at weaning. In Experiment One, one pair of liveweight (LW)-matched piglets per litter from first and third lactation sows received 2 ml of a 0 (Control) or 463 nmol/ml spermine solution at 14, 16, 18, 20 and 22 days of age (n=6 piglets/treatment per parity). Villus height and crypt depth in the duodenum and jejunum were measured at weaning (day 23 postpartum). In Experiment Two, piglets suckling 18 first and 18 third lactation sows were used. Within each litter, piglets received 2 ml of either water (Control), 463 nmol/ml spermine solution or 2013 nmol/ml spermidine solution at 14, 16, 18, 22 and 24 days of age (n=54 piglets/treatment per sow parity). Piglets were weighed individually at 14, 18, 24 (weaning) and 61 days of age. In Experiment One, oral spermine supplementation resulted in a 41% increase in villus height, a 21% decrease in crypt depth and 79% decrease in the villus height : crypt depth ratio compared with control piglets (P<0.01). In Experiment Two, spermine and spermidine-supplemented piglets suckling first lactation sows grew faster (P<0.05) between days 14 and 18 postpartum than control piglets: 0.230+/-0.011 and 0.227+/-0.012 v. 0.183+/-0.012 kg/day, respectively. Spermine supplementation tended (P<0.1) to increase piglet LW gain from weaning to day 37 post-weaning compared with control piglets (0.373+/-0.009 v. 0.341+/-0.010 kg/day). In conclusion, spermine supplementation increased villus height at weaning, and appears to have the potential to improve the pre- and post-weaning growth of conventionally weaned piglets. PMID- 26997173 TI - Special Issue: "Polyphenols and health". PMID- 26997175 TI - The Importance of Methodological Meta-Analyses and a Call to Assess Current and Former Drinking Patterns: A Commentary on Stockwell et al. (2016). PMID- 26997174 TI - Do "Moderate" Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta Analysis of Alcohol Consumption and All-Cause Mortality. AB - OBJECTIVE: Previous meta-analyses of cohort studies indicate a J-shaped relationship between alcohol consumption and allcause mortality, with reduced risk for low-volume drinkers. However, low-volume drinkers may appear healthy only because the "abstainers" with whom they are compared are biased toward ill health. The purpose of this study was to determine whether misclassifying former and occasional drinkers as abstainers and other potentially confounding study characteristics underlie observed positive health outcomes for lowvolume drinkers in prospective studies of all-cause mortality. METHOD: A systematic review and meta-regression analysis of studies investigating alcohol use and mortality risk after controlling for quality-related study characteristics was conducted in a population of 3,998,626 individuals, among whom 367,103 deaths were recorded. RESULTS: Without adjustment, meta-analysis of all 87 included studies replicated the classic J-shaped curve, with low-volume drinkers (1.3-24.9 g ethanol per day) having reduced mortality risk (RR = 0.86, 95% CI [0.83, 0.90]). Occasional drinkers (<1.3 g per day) had similar mortality risk (RR = 0.84, 95% CI [0.79, 0.89]), and former drinkers had elevated risk (RR = 1.22, 95% CI [1.14, 1.31]). After adjustment for abstainer biases and quality-related study characteristics, no significant reduction in mortality risk was observed for low-volume drinkers (RR = 0.97, 95% CI [0.88, 1.07]). Analyses of higher-quality bias-free studies also failed to find reduced mortality risk for low-volume alcohol drinkers. Risk estimates for occasional drinkers were similar to those for low- and medium volume drinkers. CONCLUSIONS: Estimates of mortality risk from alcohol are significantly altered by study design and characteristics. Meta-analyses adjusting for these factors find that low-volume alcohol consumption has no net mortality benefit compared with lifetime abstention or occasional drinking. These findings have implications for public policy, the formulation of low-risk drinking guidelines, and future research on alcohol and health. PMID- 26997176 TI - Why Do Alcohol's Assumed Benefits Have Any Role in Policymaking? PMID- 26997177 TI - All-Cause Mortality Risks for "Moderate Drinkers": What Are the Implications for Burden-of-Disease Studies and Low Risk-Drinking Guidelines? PMID- 26997179 TI - Stress Reactivity as a Prospective Predictor of Risky Substance Use During Adolescence. AB - OBJECTIVE: Youth who report risky substance use and who have a familial history of substance use disorders (SUDs) are at increased risk for developing SUDs themselves later in life. Physiological stress reactivity may be a potential biological mechanism underlying this increased risk. In the current study, we examined (a) whether physiological stress reactivity to a psychosocial stressor was prospectively related to risky substance use later in adolescence and (b) whether this relation was moderated by a familial history of SUDs. METHOD: Youth from the general population (n = 220) and the children of a parent/parents with an SUD (CPSUDs; n = 60) participated in a psychosocial stress procedure at Time 1. Cortisol and heart rate reactivity were measured during the procedure. Four years later, on average, risky substance use was self-reported (Time 2). RESULTS: Logistic regression analyses showed that youth who had lower cortisol reactivity at Time 1 were more likely to report risky substance use at Time 2. Heart rate reactivity was not related to risky substance use at Time 2, and the relation between stress reactivity and risky substance use was not more pronounced in CPSUDs compared with youth from the general population. These analyses were controlled for alcohol use at Time 1. CONCLUSIONS: The present findings suggest hyporeactivity of the hypothalamic-pituitary-adrenal axis in youth who are more likely to engage in risky substance use later in adolescence. These individuals may be inherently hypoaroused, which leads them to seek out substances in order to achieve a more normalized level of arousal. PMID- 26997180 TI - DISC1 as a Possible Genetic Contribution to Opioid Dependence in a Polish Sample. AB - OBJECTIVE: Disrupted-in-schizophrenia 1 (DISC1) has been linked to vulnerability to a variety of psychiatric disorders and neuropsychiatric phenotypes. However, DISC1 has not been frequently examined as a potential risk factor for substance dependence. An association between opioid dependence and DISC1 rs2738888 polymorphism has been recently reported. In addition, opioid dependence was associated with rs6419156 located close to the protein phosphatase 3 catalytic subunit alpha isoform (PPP3CA) gene. The aim of the present study was to examine the associations between opioid dependence with rs2738888 and rs6419156 in an independent sample. METHOD: The selected polymorphisms were genotyped in a sample of 392 individuals (69.9% male) diagnosed as alcohol- and/or opioid-dependent. A control group (n = 257; 67.7% male) was derived from the Polish National Health Survey (N = 14,350). RESULTS: The frequency of rs2738888 C allele was higher in controls than in opioid-dependent cases (OR = 0.65, p = .045). Phenotypic oriented analyses performed within opioid-dependent individuals revealed the association between lifetime suicide attempt and rs2738888. The C allele of rs2738888 had a protective effect on lifetime suicide attempt in opioid-dependent patients (OR = 0.25, p = .003). Rs6419156 was not associated with substance dependence in the examined sample. CONCLUSIONS: The DISC1 may play an important role in vulnerability to opioid dependence. In addition, DISC1 may also be a genetic risk factor for suicide attempt in opioid-dependent individuals. PMID- 26997182 TI - Early Trajectories of Alcohol and Other Substance Use Among Youth From Rural Communities Within the Cherokee Nation. AB - OBJECTIVE: This research examines gender and racial/ethnic differences in substance use trajectories during early adolescence among American Indian and non Native adolescents. METHOD: Substance use trajectories were evaluated among 684 adolescents (50% female, 51% American Indian) across five assessments over 9th and 10th grades. Youth were drawn from six rural towns within the Cherokee Nation, a nonreservation tribal jurisdiction that includes a high proportion of American Indians embedded within a predominantly White population. Past-month substance use was based on self-report and was dichotomized into "used" versus "did not use," with the exception of alcohol, which was trichotomized into "none," "1 or 2 days," or "3-30 days." RESULTS: Using growth mixture modeling with full-information maximum-likelihood estimation, we determined that between two and three different trajectory classes best described the data for each substance. Males had a higher probability compared with females of following a trajectory of chewing tobacco use (20% vs. 6%, respectively) and using multiple substances (24% vs. 19%, respectively). Females had a higher probability compared with males of following a trajectory of prescription drug misuse (11% vs. 6%, respectively). Individuals who followed trajectories of alcohol use or heavy drinking were also more likely to follow trajectories of other substance use. CONCLUSIONS: Identifying gender and racial/ethnic differences in patterns of substance use at this stage of development will inform gender-sensitive and ethnically sensitive prevention programs targeting specific substance use. These results will be particularly informative given the lack of evidence regarding trajectories of substance initiation within largely American Indian populations. PMID- 26997183 TI - Assessing the Impact of Twenty Underage Drinking Laws. AB - OBJECTIVE: Over the last two decades, many states have adopted several of the 20 laws that aim to control youth access to and possession of alcohol and prevent underage drinking in the United States. However, many of these laws have not been evaluated since their adoption. The objective of this study was to determine which minimum legal drinking age 21 (MLDA-21) laws currently have an effect on underage drinking-and-driving fatal crashes. METHOD: We updated the effective dates of the 20 MLDA-21 laws examined in this study and used scores of each law's strengths and weaknesses. Our structural equation model included the 20 MLDA-21 laws, impaired driving laws, seat belt safety laws, economic strength, driving exposure, beer consumption, and fatal crash ratios of drinking-to-nondrinking drivers under age 21. RESULTS: Nine MLDA-21 laws were associated with significant decreases in fatal crash ratios of underage drinking drivers: possession of alcohol (-7.7%), purchase of alcohol (-4.2%), use alcohol and lose your license ( 7.9%), zero tolerance .02 blood alcohol concentration limit for underage drivers (-2.9%), age of bartender >=21 (-4.1%), state responsible beverage service program (-3.8%), fake identification support provisions for retailers (-11.9%), dram shop liability (-2.5%), and social host civil liability (-1.7%). Two laws were associated with significant increases in the fatal crash ratios of underage drinking drivers: prohibition of furnishing alcohol to minors (+7.2%) and registration of beer kegs (+9.6%). CONCLUSIONS: The nine effective MLDA-21 laws are estimated to be currently saving approximately 1,135 lives annually, yet only five states have enacted all nine laws. If all states adopted these nine effective MLDA-21 laws, it is estimated that an additional 210 lives could be saved every year. PMID- 26997181 TI - CHRNA5/A3/B4 Variant rs3743078 and Nicotine-Related Phenotypes: Indirect Effects Through Nicotine Craving. AB - OBJECTIVE: Nicotine craving is considered an important element in the persistence of cigarette smoking, but little is known about the role of craving in the widely recognized association between variants mapped to the neuronal nicotinic acetylcholine receptor (CHRN) genes on chromosome 15 and nicotine phenotypes. METHOD: The associations between CHRNA5-CHRNA3-CHRNB4 variants and cigarettes per day (CPD), the Fagerstrom Test for Nicotine Dependence (FTND), and craving were analyzed in data from 662 lifetime smokers from an Israeli adult Jewish household sample. Indirect effects of genotype on nicotine phenotypes through craving were formally tested using regression and bootstrapping procedures. RESULTS: At CHRNA3, allele G of rs3743078 was associated with increased craving, CPD, and FTND scores: Participants with one or two copies of the G allele had, on average, higher scores on the craving scale (p = .0025), more cigarettes smoked (p = .0057), and higher scores on the FTND (p =.0024). With craving in the model, variant rs3743078 showed a significant indirect effect through craving on CPD (p = .0026) and on FTND score (p = .0024). A sizeable proportion of the total rs3743078 effect on CPD (56.4%) and FTND (65.2%) was indirect through craving. CONCLUSIONS: These results suggest that nicotine craving may play a central role in nicotine use disorders and may have utility as a therapeutic target. PMID- 26997184 TI - Effects of Economic Disruptions on Alcohol Use and Problems: Why Do African Americans Fare Worse? AB - OBJECTIVE: This study tested a model of the effects of recession-related job loss on alcohol use disorder (AUD) and examined why African Americans who lost their jobs during the 2008-2009 recession were at increased risk for AUD relative to Whites. We hypothesized that (a) job loss would be positively associated with psychological distress (i.e., higher levels of depressive symptoms) and increased drunkenness, and (b) low levels of family social support and experiences of racial stigma would exacerbate the effects of job loss on distress, especially among African Americans and Hispanics. METHOD: Data were drawn from the 2010 U.S. National Alcohol Survey (NAS), a cross-sectional survey of the U.S. general population. Using data from the 2010 NAS (telephone survey of 1,111 African American, 964 Hispanic, and 3,133 White adults), we conducted simultaneous path modeling in Mplus to test mediation and moderation hypotheses. Our key outcome was AUD as measured by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: Recession-related job loss was significantly associated with AUD through its effects on increased drunkenness, and the associations were positive for Whites, stronger for African Americans than Whites, and nonexistent for Hispanics. Job loss was associated with distress in the overall sample, and distress was positively associated with drunkenness among African Americans only, suggesting that distress is another pathway by which job loss affects AUD among African Americans. Higher levels of family social support mitigated the effects of job loss on psychological distress, and this relationship did not differ by race/ethnicity. CONCLUSIONS: During economic downturns, increased stress and heavy drinking are important pathways through which recession-related job loss can lead to greater AUD among African Americans relative to Whites. PMID- 26997185 TI - Monthly Estimates of Alcohol Drinking During Pregnancy: United States, 2002-2011. AB - OBJECTIVE: Taking a step beyond prior alcohol research on pregnancy trimesters, we produced pregnancy month-specific drinking estimates for women in the United States in order to shed light on time variations of alcohol drinking during pregnancy, as might be determined by alcohol dependence. We posited that (a) pregnancy might prompt cessation of drinking soon after pregnancy status is discovered, a finding obscured in trimester-specific estimates, and (b) a possible alcohol-dependence effect on drinking persistence among pregnant women might be observed via the monthly approach. METHOD: Data are from the 2002-2011 National Surveys on Drug Use and Health (Restricted-Data Analysis System [R DAS]), with large nationally representative samples of U.S. civilians, including 12- to 44-year-old females stratified by pregnancy status and month of pregnancy, and with assessment of recent alcohol dependence as well as heavy episodic drinking (HED). RESULTS: Pregnancy's possibly protective constraints on drinking can be seen as early as Month 2. We observed considerable variability of drinking prevalence (%) before Trimester 1 ended, with no appreciable variation across Months 4-9. A possible alcohol-dependence effect on drinking persistence is seen when the contrast is made in relation to expected values for pregnant women without alcohol dependence. CONCLUSIONS: We detected a possibly ameliorative pregnancy effect on alcohol use and HED, with variation in drinking prevalence across the months of the first trimester. Alcohol dependence might be affecting drinking persistence among pregnant women, but this effect cannot account for the drinking persistence observed here. PMID- 26997186 TI - Other- and Self-Directed Forms of Violence and Their Relationship With Number of Substance Use Disorder Criteria Among Youth Ages 12-17: Results From the National Survey on Drug Use and Health. AB - OBJECTIVE: The purpose of this study was to examine the associations between the number of substance use disorder (SUD) criteria as listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and other- and self directed forms of violence among youth ages 12-17 in the general population. METHOD: Data were obtained from the National Survey on Drug Use and Health pooled across survey years 2008-2013, with a combined sample of 108,560 respondents ages 12-17. Violence categories defined by suicide attempt (self-directed) and attacking someone with the intent for serious injury (other-directed) were categorized as follows: none, self-directed only, other-directed only, and combined self-/other-directed. Multinomial logistic regression estimated odds ratios of the increased number of criteria for alcohol, marijuana, and other illicit drug use, and nicotine dependence for each violence category, by controlling for sociodemographics and criminal justice involvement. RESULTS: The multivariable model indicates that increased number of SUD criteria confers significantly higher odds for each violence category versus no violence. For combined violence versus self-directed violence, male gender, non-Hispanic Black and mixed race (with non-Hispanic White as referent), nicotine dependence, increased number of alcohol use disorder criteria, and other drug use disorder criteria have significantly higher odds, whereas Native Hawaiian/Pacific Islander and age have significantly lower odds. For combined violence versus other directed violence, non-Hispanic mixed race and the increased number of other drug use disorder criteria have significantly higher odds, whereas male gender, non Hispanic Black and Native Hawaiian/Pacific Islander, and Hispanic have significantly lower odds. CONCLUSIONS: The identification of the combined self /other-directed violence in the general population provides additional support for clinical studies that established associations between self- and other directed violent behaviors. Prevention and treatment programs need to address both instances of violence and suicidality. PMID- 26997187 TI - Bidirectional Associations Between Cannabis Use and Depressive Symptoms From Adolescence Through Early Adulthood Among At-Risk Young Men. AB - OBJECTIVE: Previous studies have established a relationship between cannabis use and affective problems among adolescents and young adults; however, the direction of these associations remains a topic of debate. The present study sought to examine bidirectional associations between cannabis use and depressive symptoms, specifically testing the validity of two competing hypotheses: the cannabis effect hypothesis, which suggests that cannabis use contributes to the onset of later depressive symptoms; and the self-medication hypothesis, which posits that individuals increase their use of a substance to alleviate distressing psychological symptoms. METHOD: Participants in this study were 264 low socioeconomic-status males assessed at ages 17, 20, and 22. Cross-lag panel models were fit to test bidirectional associations between cannabis use frequency and depressive symptoms across the transition from adolescence to early adulthood. In addition, analyses were conducted within two high-risk subsamples to examine whether associations between cannabis use frequency (ranging from never used to daily use) and depressive symptoms differed among regular cannabis users (used cannabis more than once per week) or subjects reporting at least mild levels of depressive symptoms. RESULTS: Cannabis use and depressive symptoms were concurrently correlated. Cannabis use predicted increases in later depressive symptoms, but only among the mild-depression subsample. Depressive symptoms predicted only slight increases in later cannabis use, among the subsample of regular cannabis users. CONCLUSIONS: Temporal patterns of cannabis use and depressive symptoms provide evidence for the cannabis effect but limited evidence for the self-medication hypothesis. Adolescents higher in depressive symptoms may be vulnerable to the adverse psychological effects of using cannabis. Results are discussed in terms of implications for basic research, prevention, and intervention. PMID- 26997188 TI - Marijuana Use Predicts Cognitive Performance on Tasks of Executive Function. AB - OBJECTIVE: Despite growing evidence that chronic marijuana use is associated with cognitive impairment, particularly when use is initiated at an early age, national trends demonstrate significant decreases in the perceived risk of marijuana corresponding with increased use, especially among youth. The current study assessed the impact of marijuana use on executive function and whether patterns of marijuana use, including earlier age at onset, higher frequency, and increased magnitude of use, predict impairment. METHOD: Forty-four chronic, heavy marijuana smokers (37 male, 7 female) and 32 healthy, nonsmoking control participants (20 male, 12 female) recruited from the Greater Boston area completed two assessments of executive function: the Stroop Color Word Test and Wisconsin Card Sorting Test (WCST). RESULTS: Marijuana smokers had poorer executive function relative to control participants, a between-group difference that was primarily driven by individuals with early onset of marijuana use (before age 16; n = 21); significance remained even when controlling for frequency and magnitude of use. Further, earlier age at marijuana onset and increased marijuana use predicted poorer neurocognitive performance, and perseverative errors on the WCST significantly predicted marijuana group membership. CONCLUSIONS: These findings underscore the impact of early onset of marijuana use on executive function impairment independent of increased frequency and magnitude of use. In addition, poorer performance on the WCST may serve as a neuropsychological marker for heavy marijuana users. These results highlight the need for additional research to identify predictors associated with early marijuana use, as exposure to marijuana during a period of developmental vulnerability may result in negative cognitive consequences. PMID- 26997189 TI - Risk Factors for Driving After and During Marijuana Use. AB - OBJECTIVE: Use of marijuana before or while driving significantly contributes to driving impairment and elevated risk of motor vehicle accidents; however, this risk behavior is common among users. Little is known about the etiology of driving while under the influence of marijuana. METHOD: Guided by social learning theory, this study examined marijuana outcome expectancies and other driving related cognitions as predictors of the frequency of driving after smoking marijuana (DASM) and smoking marijuana while driving (SMWD). A community sample of 151 (64% male) non-treatment-seeking frequent marijuana users completed questionnaires on variables of interest. RESULTS: Perceived driving-related peer norms (i.e., perception that fewer friends disapprove of DASM and SMWD and of riding with a driver under the influence of marijuana) were associated with lower frequency of both DASM and SMWD. Perceived dangerousness of DASM was also associated with decreased frequency of DASM. CONCLUSIONS: Our findings suggest a range of potentially important targets for interventions intended to reduce the likelihood and frequency of driving while under the influence of marijuana. PMID- 26997190 TI - Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers. AB - OBJECTIVE: This study examined the acquisition of conditioning between novel stimuli and single doses of alcohol in social drinkers. Environmental stimuli present during the consumption of alcohol or other drugs come to elicit conditioned responses that subsequently increase drug seeking. However, relatively few studies have examined the process of acquisition of these conditioned drug responses in human subjects. METHOD: We used a procedure previously developed to study acquisition of conditioned responses to a methamphetamine-associated cue. In the present study we applied the paradigm to alcohol, pairing de novo neutral cues with alcohol in social drinkers (N = 36). We obtained measures of self-report, behavioral preference, emotional reactivity (assessed using facial electromyography), and attention to specific cues paired with administration of 0.6 g/kg 95% absolute alcohol or placebo. RESULTS: After conditioning, participants showed an increase in attention toward the alcohol paired cue, and this increase was associated with ratings of liking the alcohol containing beverage during the conditioning sessions. In contrast to our previous findings with methamphetamine, the alcohol-paired cue did not elicit changes in emotional reactivity (measured by facial electromyography) or behavioral preference. CONCLUSIONS: This study extends our previous findings with a stimulant drug to alcohol and highlights possible similarities and differences in conditioning with different classes of drugs. Conditioning with alcohol was less robust than with methamphetamine, but in both cases the conditioning that did occur was related to positive subjective drug response. PMID- 26997191 TI - A Parenting Program to Promote an Alcohol-Free Childhood: Influence on Parents' Readiness to Prevent Child Sipping. AB - OBJECTIVE: This study reports effects of a parenting program to increase parents' readiness to socialize their children against early alcohol use. METHOD: A two group randomized controlled trial was conducted with a nonprobability sample of 816 mothers. Participants were recruited from school districts located primarily in North Carolina and completed telephone interviews at baseline and 6 and 18 months after delivery of a parenting program to the treatment group mothers. Mothers reported on psychological indicators of readiness to prevent child alcohol use (e.g., attitude toward child sipping) and on parenting behaviors with potential to prevent such use (e.g., setting rules about child sipping). Multivariate analysis of variance models tested program effects on composite sets of psychological and behavioral outcomes; step-down analysis identified the individual outcomes driving overall program effects. Moderation of program effects by mother's alcohol use, established beliefs about the consequences of child sipping, educational attainment, and race/ethnicity was tested. RESULTS: The program had significant overall effects on each composite set of psychological and behavioral outcomes. Effects on psychological outcomes were moderated by mother's alcohol use, beliefs about the consequences of child sipping, and educational attainment; effects on the behavioral outcomes were moderated by mother's race/ethnicity. CONCLUSIONS: The parenting program had favorable, sustained effects on targeted outcomes intended to increase parental readiness to socialize children against early alcohol use. Mothers expected to be least receptive to the program-those who, at baseline, believed that allowing children to sip alcohol can have beneficial consequences-were most changed by it. PMID- 26997193 TI - Khat Dependence, Use Patterns, and Health Consequences in Australia: An Exploratory Study. AB - OBJECTIVE: The identification of khat dependence and the association between khat dependence, use patterns, and related health problems have not been quantitatively described in Australia. The current study aimed to describe khat dependence, use patterns, and khatrelated health problems in Australian migrant communities. METHOD: A 48-item questionnaire was administered to a convenience sample of 52 participants from African migrant communities who self-reported using khat in four Australian state capital cities between April 1 and June 1, 2012. Associations between Severity of Dependence Scale for khat use (SDS-khat) screening status, use patterns, and khat-related psychological and physical health problems were assessed using multivariate loglinked Poisson regression controlling for potential sociodemographic confounders. RESULTS: Overall, 44.2% (n = 23) of the study participants screened positive on the SDS-khat, indicating probable khat dependence. Screening positive for khat dependence was associated with increased risk for khat use frequency in the last 30 days (adjusted prevalence risk ratio [APRR] = 2.26, 95% CI [1.23, 4.15], p = .009), experiencing three or more psychological health problems (APRR = 1.87, 95% CI [1.04, 3.36], p = .037), and experiencing two or more physical health problems (APRR = 1.92, 95% CI [1.13, 3.27], p = .016) after using khat. CONCLUSIONS: Screening positive on the SDS-khat is associated with increased recent khat use frequency and elevated physical and psychological health problems, providing preliminary evidence that probable khat use dependence may be associated with an increased risk of harm in Australia. Furthermore, these preliminary results support the potential utility of the SDS-khat to healthcare providers to identify those at risk for khatrelated harms. Further investigation into the relationship between khat dependence, use patterns, and related health outcomes is warranted. PMID- 26997192 TI - Evaluation of Alcohol-Related Personalized Normative Feedback With and Without an Injunctive Message. AB - OBJECTIVE: Personalized normative feedback (PNF) has been used extensively to reduce alcohol consumption, particularly among heavy drinkers. However, the majority of PNF studies have used only descriptive norms (real or perceived pervasiveness of a given behavior). The purpose of the current study was to explore the efficacy of PNF both with and without an injunctive message indicating approval or disapproval based on the participants' standing relative to other students' drinking levels. This randomized trial evaluated two brief web based alcohol intervention conditions (descriptive-norms-feedback-only condition versus a descriptive-plus-injunctive-message condition relative to an assessment only control condition). METHOD: Participants included 176 students who had reported at least one heavy drinking episode in the past month. Participants completed baseline and follow-up assessments of perceived norms and drinking. Follow-up assessments were completed at 2 weeks post-intervention by 165 (94%) participants. RESULTS: Analyses were conducted using zero-inflated negative binomial regression models. As expected, the descriptive-norms-only condition was effective in reducing drinking among heavier baseline drinkers at follow-up relative to the control condition. However, contrary to expectations, the descriptive-plus-injunctive-message condition did not predict less drinking at follow-up. CONCLUSIONS: This study was unique in using an injunctive message as an adjunct to descriptive-norms feedback within the context of drinking. Findings highlight the need for additional research into the role of defensiveness, which may serve as an impediment to using injunctive norms/messages in interventions for problematic substance use and other potentially stigmatizing behaviors. PMID- 26997194 TI - Young Adults' Exposure to Alcohol- and Marijuana-Related Content on Twitter. AB - OBJECTIVE: Twitter is among the most popular social media platforms used by young adults, yet it has been underutilized in substance use research compared with older platforms (e.g., MySpace and Facebook). We took a first step toward studying the associations between exposure to pro-alcohol- and marijuana-related content among young adults via Twitter and current heavy episodic drinking and current marijuana use, respectively. METHOD: We conducted an online survey of 587 (254 men, 333 women) Twitter users between ages 18 and 25 years in February 2014 using an online survey system that has been previously used in research on health behaviors and attitudes. RESULTS: Current heavy episodic drinking was significantly associated with higher levels of exposure to pro-alcohol content. Similarly, current marijuana use was significantly associated with higher levels of exposure to pro-marijuana content. CONCLUSIONS: Our findings suggest that in depth research regarding young adults' exposure to pro-alcohol- and marijuana related content via Twitter may provide a foundation for developing effective prevention messages on this social media platform to counter the pro-alcohol and marijuana messages. PMID- 26997196 TI - The Weakest Link: Supermarket Self-Checkout Lanes and Alcohol Sales to Minors. PMID- 26997195 TI - The Reasons for Heavy Drinking Questionnaire: Factor Structure and Validity in Alcohol-Dependent Adults Involved in Clinical Trials. AB - OBJECTIVE: People consume alcohol at problematic levels for many reasons. These different motivational pathways may have different biological underpinnings. Valid, brief measures that discriminate individuals' reasons for drinking could facilitate inquiry into whether varied drinking motivations account for differential response to pharmacotherapies for alcohol use disorders. The current study evaluated the factor structure and predictive validity of a brief measure of alcohol use motivations developed for use in randomized clinical trials, the Reasons for Heavy Drinking Questionnaire (RHDQ). METHOD: The RHDQ was administered before treatment to 265 participants (70% male) with alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, in three pharmacotherapy randomized clinical trials. Principal components analysis was used in half the sample to determine the RHDQ factor structure. This structure was verified with confirmatory factor analysis in the second half of the sample. The factors derived from this analysis were evaluated with respect to alcohol dependence severity indices. RESULTS: A two factor solution was identified. Factors were interpreted as Reinforcement and Normalizing. Reinforcement scores were weakly to moderately associated with severity, whereas normalizing scores were moderately to strongly associated with severity. In all cases in which significant associations between RHDQ scores and severity indices were observed, the relationship was significantly stronger for normalizing than for reinforcing. CONCLUSIONS: The RHDQ is a promising brief assessment of motivations for heavy alcohol use, particularly in the context of randomized clinical trials. Additional research should address factor structure stability in non-treatment-seeking individuals and the RHDQ's utility in detecting and accounting for changes in drinking behavior, including in response to intervention. PMID- 26997197 TI - 3D-printed guiding templates for improved osteosarcoma resection. AB - Osteosarcoma resection is challenging due to the variable location of tumors and their proximity with surrounding tissues. It also carries a high risk of postoperative complications. To overcome the challenge in precise osteosarcoma resection, computer-aided design (CAD) was used to design patient-specific guiding templates for osteosarcoma resection on the basis of the computer tomography (CT) scan and magnetic resonance imaging (MRI) of the osteosarcoma of human patients. Then 3D printing technique was used to fabricate the guiding templates. The guiding templates were used to guide the osteosarcoma surgery, leading to more precise resection of the tumorous bone and the implantation of the bone implants, less blood loss, shorter operation time and reduced radiation exposure during the operation. Follow-up studies show that the patients recovered well to reach a mean Musculoskeletal Tumor Society score of 27.125. PMID- 26997198 TI - Kinetic Study of Hydrogen Evolution Reaction over Strained MoS2 with Sulfur Vacancies Using Scanning Electrochemical Microscopy. AB - Molybdenum disulfide (MoS2), with its active edge sites, is a proposed alternative to platinum for catalyzing the hydrogen evolution reaction (HER). Recently, the inert basal plane of MoS2 was successfully activated and optimized with excellent intrinsic HER activity by creating and further straining sulfur (S) vacancies. Nevertheless, little is known about the HER kinetics of those S vacancies and the additional effects from elastic tensile strain. Herein, scanning electrochemical microscopy was used to determine the HER kinetic data for both unstrained S vacancies (formal potential Ev0 = -0.53 VAg/AgCl, electron transfer coefficient alphav = 0.4, electron-transfer rate constant kv0 = 2.3 * 10(-4) cm/s) and strained S vacancies (Esv0= -0.53 VAg/AgCl, alphasv = 0.4, ksv0 = 1.0 * 10(-3) cm/s) on the basal plane of MoS2 monolayers, and the strained S vacancy has an electron-transfer rate 4 times higher than that of the unstrained S vacancy. This study provides a general platform for measuring the kinetics of two-dimensional material-based catalysts. PMID- 26997199 TI - Characterization and functional analysis of a tandem-repeat galectin-9 in large yellow croaker Larimichthys crocea. AB - Galectins are a family of endogenous lectins with beta-galactosides affinity, playing significant roles in the innate immunity of vertebrates and invertebrates. In this report, a new galectin-9 cDNA was identified and characterized in large yellow croaker Larimichthys crocea (designated as LcGal 9). The complete cDNA sequence of LcGal-9 was 1795 bp, with an open reading frame (ORF) of 1032 bp encoding 343 amino acids. The putative LcGal-9 protein contained two carbohydrate recognition domains (CRDs) connected by a linker peptide, with each carrying two conserved beta-galactoside binding motifs H-NPR and WG-EE-, and it possessed neither a signal peptide nor a transmembrane domain. LcGal-9 protein shared 43-74% identity with galectin-9 sequences from other species. The qRT-PCR analysis revealed that LcGal-9 mRNA was constitutively expressed in all tissues examined, predominately expressed in liver, spleen, gill, kidney, head-kidney and intestine. Western blot analysis showed that LcGal-9 protein was highly expressed in liver, spleen, intestine, kidney, head-kidney, skin, gill, and heart, but not detected in muscle and plasma. LcGal-9 mRNA transcripts were induced by poly I:C in the liver (from 6 h to 48 h), spleen (at 12 h) and head-kidney (at 12 h and 24 h). In contrast, Vibrio parahaemolyticus caused a significant down-regulation in these three tissues, except for in spleen of 48 h and head-kidney of 3 h. Post infection with Cryptocaryon irritans, the transcripts were dramatically up regulated in gill, skin, spleen and head-kidney during initial infection period, while significant down-regulation afterward was also observed both in spleen and head-kidney. The recombinant LcGal-9 (named as rLcGal-9) purified from Escherichia coli BL21 (DE3) demonstrated hemagglutination against human, rabbit and L. crocea in a Ca(2+)-independent manner, which was inhibited by alpha Lactose and LPS. The results of bacterial agglutination assays showed that rLcGal 9 was able to agglutinate Gram-negative bacteria V. alginolyticus and Aeromonas hydrophila in a Ca(2+)-independent manner. By immunohistochemistry assay, significant increases of LcGal-9 protein appeared in the spleen stimulated with poly I:C (for 12 h) and V. parahaemolyticus (for 48 h) compared with the control. Based on the collective data, LcGal-9 might play an important role in innate immune responses, especially defense against Gram-negative bacteria in L. crocea. PMID- 26997200 TI - Understanding the interaction between Betanodavirus and its host for the development of prophylactic measures for viral encephalopathy and retinopathy. AB - Over the last three decades, the causative agent of viral encephalopathy and retinopathy (VER) disease has become a serious problem of marine finfish aquaculture, and more recently the disease has also been associated with farmed freshwater fish. The virus has been classified as a Betanodavirus within the family Nodaviridae, and the fact that Betanodaviruses are known to affect more than 120 different farmed and wild fish and invertebrate species, highlights the risk that Betanodaviruses pose to global aquaculture production. Betanodaviruses have been clustered into four genotypes, based on the RNA sequence of the T4 variable region of their capsid protein, and are named after the fish species from which they were first derived i.e. Striped Jack nervous necrosis virus (SJNNV), Tiger puffer nervous necrosis virus (TPNNV), Barfin flounder nervous necrosis virus (BFNNV) and Red-spotted grouper nervous necrosis virus (RGNNV), while an additional genotype turbot betanodavirus strain (TNV) has also been proposed. However, these genotypes tend to be associated with a particular water temperature range rather than being species-specific. Larvae and juvenile fish are especially susceptible to VER, with up to 100% mortality resulting in these age groups during disease episodes, with vertical transmission of the virus increasing the disease problem in smaller fish. A number of vaccine preparations have been tested in the laboratory and in the field e.g. inactivated virus, recombinant proteins, virus-like particles and DNA based vaccines, and their efficacy, based on relative percentage survival, has ranged from medium to high levels of protection to little or no protection. Ultimately a combination of effective prophylactic measures, including vaccination, is needed to control VER, and should also target larvae and broodstock stages of production to help the industry deal with the problem of vertical transmission. As yet there are no commercial vaccines for VER and the aquaculture industry eagerly awaits such a product. In this review we provide an overview on the current state of knowledge of the disease, the pathogen, and interactions between betanodavirus and its host, to provide a greater understanding of the multiple factors involved in the disease process. Such knowledge is needed to develop effective methods for controlling VER in the field, to protect the various aquaculture species farmed globally from the different Betanodavirus genotypes to which they are susceptible. PMID- 26997201 TI - Molecular cloning, structure and expressional profiles of two novel single-exon genes (PoCCR6A and PoCCR6B) in the Japanese flounder (Paralichthys olivaceus). AB - CCR6 is an important binding receptor of CCL20 and beta-defensins, and has multiple functions in the innate and acquired immune responses. In this study, we cloned the PoCCR6A and PoCCR6B genes of the Japanese flounder and studied the gene structure and expression patterns of these two genes in bacterial infection. The full-length PoCCR6A cDNA is 1415 bp and the open reading frame (ORF) is 1113 bp, encoding a 370-amino-acid peptide. The full-length PoCCR6B cDNA is 2193 bp and the ORF is 1029 bp, encoding a 363-amino-acid peptide. The structures of PoCCR6A and PoCCR6B indicate that they are single-exon genes. The predicted proteins encoded by PoCCR6A and PoCCR6B have the typical G-protein-coupled receptor (GPCR) family signature of seven transmembrane domains and several conserved structural features. A tissue distribution analysis showed that PoCCR6A is predominately expressed in the intestine, gill, and blood, and PoCCR6B in the gill, spleen, and liver. The expression patterns of the two chemokine receptors were analyzed during bacterial infection. In spleen and kidney, the expression of PoCCR6A was significantly upregulated at 24 h after infection, whereas the expression of PoCCR6B was steady at these time points. While in intestine, both of them were upregulated at 6 h-12 h after infection, and in gill the expression levels of them were upregulated at 24 h. The patterns of expression suggested that PoCCR6A and PoCCR6B play an important role in the immune response of the Japanese flounder, especially in the mucosal tissues. PMID- 26997202 TI - Host-derived probiotics Enterococcus casseliflavus improves resistance against Streptococcus iniae infection in rainbow trout (Oncorhynchus mykiss) via immunomodulation. AB - The present study evaluated the benefits of dietary administration of host derived candidate probiotics Enterococcus casseliflavus in juvenile rainbow trout Oncorhynchus mykiss. Experimental diets were prepared by incorporating the microorganisms in the basal feed at 3 inclusion levels (i.e. 10(7) CFU g(-1) of feed [T1], 10(8) CFU g(-1) of feed [T2], 10(9) CFU g(-1) of feed [T3]). The probiotic feeds were administered for 8 weeks, with a group fed with the basal diet serving as control. The effects on growth performance, gut health, innate immunity and disease resistance were evaluated. Results showed that growth performance parameters were significantly improved in T2 and T3 groups. Activities of digestive enzymes such as trypsin and lipase were significantly higher in these two groups as well. Gut micro-ecology was influenced by probiotic feeding as shown by the significant increase in intestinal lactic acid bacteria and total viable aerobic counts in T2 and T3. Humoral immunity was impacted by dietary probiotics as total serum protein and albumin were significantly elevated in T3. The levels of serum IgM significantly increased in all probiotic fed groups at week 8; with the T3 group registering the highest increment. Respiratory burst activity of blood leukocytes were significantly improved in T2 and T3. Hematological profiling further revealed that neutrophil counts significantly increased in all probiotic fed groups. Challenge test showed that probiotic feeding significantly improved host resistance to Streptococcus iniae infection, specifically in T2 and T3 where a considerable modulation of immune responses was observed. Taken together, this study demonstrated E. casseliflavus as a potential probiotics for rainbow trout with the capability of improving growth performance and enhancing disease resistance by immunomodulation. PMID- 26997203 TI - The confounding complexity of innate immune receptors within and between teleost species. AB - Teleost genomes encode multiple multigene families of immunoglobulin domain containing innate immune receptors (IIIRs) with unknown function and no clear mammalian orthologs. However, the genomic organization of IIIR gene clusters and the structure and signaling motifs of the proteins they encode are similar to those of mammalian innate immune receptor families such as the killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LILRs), Fc receptors, triggering receptors expressed on myeloid cells (TREMs) and CD300s. Teleost IIIRs include novel immune-type receptors (NITRs); diverse immunoglobulin domain containing proteins (DICPs); polymeric immunoglobulin receptor-like proteins (PIGRLs); novel immunoglobulin-like transcripts (NILTs) and leukocyte immune-type receptors (LITRs). The accumulation of genomic sequence data has revealed that IIIR gene clusters in zebrafish display haplotypic and gene content variation. This intraspecific genetic variation, as well as significant interspecific variation, frequently confounds the identification of definitive orthologous IIIR sequences between teleost species. Nevertheless, by defining which teleost lineages encode (and do not encode) different IIIR families, predictions can be made about the presence (or absence) of specific IIIR families in each teleost lineage. It is anticipated that further investigations into available genomic resources and the sequencing of a variety of multiple teleost genomes will identify additional IIIR families and permit the modeling of the evolutionary origins of IIIRs. PMID- 26997204 TI - A prospective, multicentre study on the use of epidermal grafts to optimise outpatient wound management. AB - Current wound management through the use of a split-thickness skin graft often requires hospital admission, a period of immobility, attentive donor site wound care and pain management. This study evaluates the feasibility of using a novel epidermal graft-harvesting device (CelluTome) that allows pain-free epidermal skin grafting in the outpatient clinic setting. A prospective series of 35 patients was performed in 2 centres, involving 10 acute and 25 chronic wounds. All patients were subjected to epidermal grafting in the outpatient specialist clinic, without the use of anaesthesia, and allowed to return home after the procedure. Completely healed wounds were noted in 22 patients (62.9%). The overall mean time for 50% and 100% reduction in wound size was 3.31 +/- 2.33 and 5.91 +/- 3.48 weeks, respectively. There was no significant difference in healing times between the acute and chronic wounds (50% reduction in wound size; acute 2.20 +/- 0.91 weeks versus chronic 3.73 +/- 2.63 weeks, P = 0.171. Hundred percent reduction in wound size; acute 4.80 +/- 1.61 weeks versus chronic 6.83 +/ 4.47 weeks, P = 0.183). The mean time for donor site healing was 5.49 +/- 1.48 days. The mean pain score during graft harvest was 1.42 +/- 0.95, and the donor site Vancouver Scar Scale was 0 for all cases at 6 weeks. This automated device offers autologous skin harvesting in the outpatient setting with minimal or no pain and a scar free donor site, equally benefiting both the acute and chronic wounds. It has the potential to save NHS resources by eliminating the need for theatre space and a hospital bed while at the same time benefiting patient care. PMID- 26997206 TI - Occipital Neuralgia Diagnosis and Treatment: The Role of Ultrasound. AB - BACKGROUND: Occipital neuralgia is a form of neuropathic type of pain in the distribution of the greater, lesser, or third occipital nerves. Patients with intractable occipital neuralgia do not respond well to conservative treatment modalities. This group of patients represents a significant therapeutic challenge and may require interventional or invasive therapeutic approaches. PURPOSE: Occipital neuralgia frequently occurs as a result of nerve entrapment or irritation by a tight muscle or vascular structure, or nerve trauma during whiplash injury. Although the entrapment theory is most commonly accepted, it lacks strong clinical evidence to support it. Accordingly, the available interventional approaches have been targeting the accessible part of the occipital nerve rather than the entrapped part. CONCLUSION: Bedside sonography is an excellent imaging modality for soft tissue structures. Ultrasound not only allows distinguishing normal from abnormal entrapped occipital nerves, it can identify the level and the cause of entrapment as well. Ultrasound guidance allows precise occipital nerve blocks and interventions at the level of the "specific" entrapment location rather than into the site of "presumed" entrapment. PMID- 26997205 TI - Metal-free C(sp(3))-H functionalization: oxidative carbo-oxygenation of alpha diazo carbonyls via radical dediazotization. AB - A novel three-component carbo-oxygenation of alpha-diazo carbonyls for flexible synthesis of unprecedented alpha-aminooxy-beta-amino ketones has been established through metal-free C(sp(3))-H functionalization from readily accessible N,N dimethylanilines and N-hydroxyphthalimide. The reaction pathway involves an in situ-generated phthalimide N-oxyl radical-triggered dediazotization/radical coupling sequence, leading to C-O and C-C bond formation. PMID- 26997209 TI - Sex Differences in the Association Between Regular Physical Activity and Incident Atrial Fibrillation: A Meta-analysis of 13 Prospective Studies. AB - Several studies investigated the role of physical activity in atrial fibrillation (AF), but the results remain controversial. We aimed to estimate the association between physical activity and incident AF, as well as to determine whether a sex difference existed. We systematically retrieved relevant studies from Cochrane Library, PubMed, and ScienceDirect through December 1, 2015. Data were abstracted from eligible studies and effect estimates pooled using a random-effects model. Thirteen prospective studies fulfilled inclusion criteria. For primary analysis, neither total physical activity exposure (relative risk [RR]: 0.98, 95% confidence interval [CI]: 0.90-1.06, P = 0.62) nor intensive physical activity (RR: 1.07, 95% CI: 0.93-1.25, P = 0.41) was associated with a significant increased risk of AF. In the country-stratified analysis, the pooled results were not significantly changed. However, in the sex-stratified analysis, total physical activity exposure was associated with an increased risk of AF in men (RR: 1.18, 95% CI: 1.02-1.37), especially at age <50 years (RR: 1.58, 95% CI: 1.28-1.95), with a significantly reduced risk of AF in women (RR: 0.92, 95% CI: 0.87-0.97). Additionally, male individuals with intensive physical activity had a slightly higher (although statistically nonsignificant) risk of developing AF (RR: 1.12, 95% CI: 0.99-1.28), but there was a significantly reduced risk of incident AF in women (RR: 0.92, 95% CI: 0.86-0.98). Published literature supports a sex difference in the association between physical activity and incident AF. Increasing physical activity is probably associated with an increased risk of AF in men and a decreased risk in women. PMID- 26997208 TI - A Water-Soluble Tetraazaperopyrene Dye as Strong G-Quadruplex DNA Binder. AB - The interactions of the water-soluble tetraazaperopyrene dye 1 with ct-DNA, duplex-[(dAdT)12 ?(dAdT)12 ], duplex-[(dGdC)12 ?(dGdC)12 ] as well as with two G quadruplex-forming sequences, namely the human telomeric 22AG and the promotor sequence c-myc, were investigated by means of UV/visible and fluorescence spectroscopy, isothermal titration calorimetry (ITC) and molecular docking studies. Dye 1 exhibits a high affinity for G-quadruplex structures over duplex DNA structures. Furthermore, the ligand shows promising G-quadruplex discrimination, with an affinity towards c-myc of 2*10(7) m(-1) (i.e., Kd =50 nm), which is higher than for 22AG (4*10(6) m(-1) ). The ITC data reveal that compound 1 interacts with c-myc in a stoichiometric ratio of 1:1 but also indicate the presence of two identical lower affinity secondary binding sites per quadruplex. In 22AG, there are two high affinity binding sites per quadruplex, that is, one on each side, with a further four weaker binding sites. For both quadruplex structures, the high affinity interactions between compound 1 and the quadruplex-forming nucleic acid structures are weakly endothermic. Molecular docking studies suggest an end-stacking binding mode for compound 1 interacting with quadruplex structures, and a higher affinity for the parallel conformation of c-myc than for the mixed-hybrid conformation of 22AG. In addition, docking studies also suggest that the reduced affinity for duplex DNA structures is due to the non-viability of an intercalative binding mode. PMID- 26997207 TI - Prefrontal infralimbic cortex mediates competition between excitation and inhibition of body movements during pavlovian fear conditioning. AB - The infralimbic subregion of the prefrontal cortex (IL) is broadly involved in behavioral flexibility, risk assessment, and outcome reinforcement. In aversive conditioning tasks, the IL has been implicated in fear extinction and in mediating transitions between Pavlovian and instrumental responses. Here we examine the role of the IL in mediating transitions between two competing Pavlovian fear responses, conditioned motor inhibition (CMI) and conditioned motor excitation (CME). Rats were trained to fear an auditory conditioned stimulus (CS) by pairing it with periorbital shock to one eyelid (the unconditioned stimulus [US]). Trained animals exhibited CMI responses (movement suppression) to the CS when they had not recently encountered the US (>24 hr), but, after recent encounters with the US (<5 min), the CS evoked CME responses (turning in circles away from anticipated shock). Animals then received bilateral infusions of muscimol or picrotoxin to inactivate or hyperactivate the IL, respectively. Neither drug reliably affected CMI responses, but there was a bidirectional effect on CME responses; inactivation of the IL attenuated CME responses, whereas hyperactivation potentiated CME responses. These results provide evidence that activation of the IL may promote behavioral strategies that involve mobilizing the body and suppress strategies that involve immobilizing the body. (c) 2016 Wiley Periodicals, Inc. PMID- 26997211 TI - Application of the Surgical Apgar Score to Microvascular Head and Neck Reconstruction. AB - PURPOSE: The surgical Apgar score (SAS) is a recently devised risk-stratifying metric that relies on 3 intraoperative parameters to predict postoperative complications in surgical patients. The purpose of this study was to validate the SAS externally in a cohort of patients undergoing microvascular head and neck reconstruction with fibular free flaps. MATERIALS AND METHODS: A retrospective cohort study of patients undergoing head and neck microvascular reconstruction with fibular free flaps was completed. The primary predictor variable was the calculated SAS. The primary outcome variable was the presence of medical and surgical complications occurring within 30 days of surgery. Basic demographic information, comorbidity indices, and perioperative parameters were abstracted as covariates. Medical and surgical complications were categorized as minor or major depending on severity level. Univariable and multivariable logistic regression models were used to evaluate associations with 30-day postoperative complications. RESULTS: In 154 patients, the partial flap failure rate was 3% and there were no complete flap failures. There were 110 patients (71%) who developed at least 1 30-day postoperative complication and 51 (33%) who developed a major complication. The median SAS was 7. The SAS was not significantly associated with the presence of any 30-day postoperative complication (odds ratio [OR] = 1.02; 95% confidence interval [CI], 0.74-1.42; P = .89) or the presence of any major postoperative complication (OR = 0.08; 95% CI, 0.59-1.09; P = .16) in a univariable setting. The SAS did not achieve statistical significance after multivariable adjustment. CONCLUSION: Despite validation in numerous other surgical specialties, the SAS might not be useful as a metric for risk stratification among patients undergoing major head and neck reconstruction with fibular free flaps. PMID- 26997210 TI - Improvement of cardiac dysfunction by bilateral surgical renal denervation in animals with diabetes induced by high fructose and high fat diet. AB - AIMS: Insulin resistance (IR) and sympathetic over-activation play a critical role in diabetic cardiomyopathy (DCM). Percutaneous renal sympathetic denervation (RDN) was tested to treat refractory hypertension. However, the benefits of RDN for DCM and IR still remain unknown. The present study aimed to investigate the effect and associated mechanisms of bilateral surgical RDN (bsRDN) on cardiac function and glucose metabolism in animals with diabetes. METHODS: Thirty-two male New Zealand white rabbits were randomly assigned to Chow (n=8, normal diet) and TEST (n=24, high-fructose fat diet [HFD]) groups. At 48 weeks after HFD feeding, animals in the TEST group were randomized to the Sham, HFD, and RDN subgroups and were fed a HFD for an additional 8 weeks. Repeated measurements of cardiac function, IR, apoptosis/autophagy, and histopathological assessment were performed at 48 and 56 weeks. RESULTS: HFD feeding for 56 weeks induced IR and diastolic cardiac dysfunction with hypertrophy in septum but well preserved eject fraction in the animals. Impaired IR further deteriorated over the time in the RDN group, featured by a more profound reduction in GLUT4 mRNA and its translocation to the plasma membrane. Successful denervation was associated with improvement of cardiac function via preventing myocardial fibrosis and over expression of procollagen III, mammalian target of rapamycin, and cardiac apoptosis. Cardiac autophagy, assessed by either electron microscopy or Western blot, was enhanced by bsRDN. CONCLUSIONS: Renal sympathetic denervation led to a significant improvement of HFD-induced cardiac dysfunction by shifting the cardiac apoptosis to autophagy, but worsening IR. Further study is required to identify the clinical benefits of RDN. PMID- 26997212 TI - The use of GRADE approach in systematic reviews of animal studies. AB - OBJECTIVE: The application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) in systematic review (SR) of animal studies can promote the translation from bench to bedside. We aim to explore the use of GRADE in SRs of animal studies. METHODS: We used a theoretical analysis method to explore the use of GRADE in SR of animal studies and applied in an SR of animal studies. Meanwhile, we presented and discussed our results in two international conferences. RESULTS: Five downgrade factors were considered as follows in SRs of animal studies: (1) Risk of bias: the SYRCLE tool can be used for assessing the risk of bias of animal studies. (2) Indirectness: we can assess indirectness in SRs of animal studies from the PICO. (3) Inconsistency: similarity of point estimates, extent of overlap of confidence intervals (CIs), and statistical heterogeneity are also suitable to evaluate inconsistency of evidence from animal studies. (4) Imprecision: optimal information size and 95% CIs are also suitable for SRs of animal studies, like those of clinical trials. (5) Publication bias: we need to consider publication bias comprehensively through the qualitative and quantitative methods. CONCLUSIONS: The methods about the use of GRADE in SR of animal studies are explicit. However, the principle about GRADE in developing the policy based on the evidence from animal studies when there is an emergency of public health. PMID- 26997213 TI - Growth parameters early in the course of pediatric inflammatory bowel disease. PMID- 26997214 TI - Treatment of nonalcoholic fatty liver disease: Where do we stand? an overview. AB - Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, the prevalence of which had progressively increased over the past 10 years where other liver diseases remained at the same prevalence rates or are expected to decrease as in the case of hepatitis C virus (HCV). The treatment of NAFLD is of prime concern to health care professionals and patients due to the significant mortality and morbidity it implies; the problem is further escalated by the fact that standard of care medications targeting NAFLD remain experimental and without evidence base. Treatment nowadays is focused on lifestyle modification and managing the comorbid associated diseases, with a possible role for some hepatic protective agents. This review presents all the medications that had been proposed and used for the treatment of NAFLD with or without scientific rationale and includes agents for weight loss, insulin sensitizers, drugs that reduce blood lipids, glucagon-mimetics, drugs that may reduce fibrosis, angiotensin receptor blockers, and medicines believed to reduce endoplasmic reticular stress such as vitamin E, ursodeoxycholic acid, and S-adenosyl methionine. A quick review of the newer agents that proved to be promising such as obeticholic acid and GFT505 and the medicines that are still in the pipeline is also presented. PMID- 26997216 TI - Correlation of HVPG level with ctp score, MELD Score, ascites, size of varices, and etiology in cirrhotic patients. AB - BACKGROUND/AIM: This study intends to determine the correlation of a patient's hepatic venous pressure gradient (HVPG) measurement with six factors: Child Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD) score, presence of ascites, size of varices, presence of variceal bleeding, and an etiology of cirrhosis. The study also aims to identify the predictors of higher HVPG measurements that can indirectly affect the prognosis of cirrhotic patients. PATIENTS AND METHODS: Thirty patients diagnosed with cirrhosis were enrolled prospectively and each patient's HVPG level was measured by the transjugular catheterization of the right or middle hepatic vein. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were measured using a 7F balloon catheter. The HVPG level was calculated as the difference between the WHVP and FHVP measurements. RESULTS: The mean HVPG level was higher in alcoholic than in nonalcoholic cirrhosis (19.5 +/- 7.3 vs 15.2 +/- 4.5 mm Hg, P = 0.13). The mean HVPG was also higher in bleeders compared with nonbleeders (18.5 +/- 5.3 vs 10.7 +/- 3.1 mmHg, P = 0.001). Patients with varices had a higher mean HVPG level than those without varices (17.4 +/- 5.8 vs 11.7 +/- 3.9 mmHg, P = 0.04). The difference among the three categories of varices (small, large, and no varices) was statistically significant (P = 0.03). In addition, the mean HVPG level was higher in patients with ascites than in those without ascites (18.7 +/- 4.7 vs 11 +/- 5.3 mmHg, P = 0.002), and it was significantly higher in patients in CTP class C (21.8 +/- 5.5 mmHg) as compared with those in CTP class B (16.9 +/ 2.9 mmHg) and CTP class A (10.5 +/- 4.1 mmHg; P <= 0.001). CONCLUSION: HVPG levels were significantly higher in patients in CTP class C as compared with those in CTP classes A and B, thereby indicating that an HVPG measurement correlates with severity of liver disease. A high HVPG level signifies more severe liver disease and can predict the major complications of cirrhosis. PMID- 26997215 TI - Impact of pediatric inflammatory bowel disease on linear growth: Data from a national cohort study in Saudi Arabia. AB - BACKGROUND/AIM: Linear growth impairment (LGI) is one of the most important features peculiar to children with inflammatory bowel disease (IBD). The aim of this report is to define the impact of IBD on the linear growth of children in the Kingdom of Saudi Arabia (KSA). SETTING AND DESIGN: Multicenter retrospective study. PATIENTS AND METHODS: Data from a cohort of newly- diagnosed children with IBD from 2003 to 2012 were analyzed retrospectively. The diagnosis of IBD was confirmed in accordance with the published criteria. Length/height for age was measured at diagnosis. The World Health Organization (WHO) reference was used and LGI was defined by length/height for age <-2 standard deviation. Chi-square test was used to test the significance of estimates and a P < 0.05 was considered significant. RESULTS: There were 374 children from 0.33 to 16 years of age, including 119 ulcerative colitis (UC) (32%), and 255 Crohn's disease (CD) (68%) patients. The prevalence of LGI was 26%, 28%, and 21% in IBD, CD, and UC, respectively. In children below 10 years, LGI was significantly more common in CD (P = 0.010), while in UC children, it was more common in older children (P = 0.011). CONCLUSION: This study demonstrates a prevalence of LGI consistent with that reported in the literature, but higher in CD children with early onset (<10 years) and in older children with UC, underscoring the importance of monitoring growth in children with IBD in the Saudi population. Prospective studies are needed to define the impact of IBD on growth velocity, puberty, and final adult stature. PMID- 26997217 TI - The evaluation of left ventricular functions with tissue doppler echocardiography in adults with celiac disease. AB - BACKGROUND/AIM: The aim of this study was to investigate the effects of celiac disease on cardiac functions using tissue Doppler echocardiography (TDE). PATIENTS AND METHODS: The study included 30 patients with celiac disease (CD) and 30 healthy volunteers. Echocardiographic examinations were assessed by conventional echocardiography and tissue Doppler imaging. The peak systolic velocity (S'm), early diastolic myocardial peak velocity (E'm), late diastolic myocardial peak velocity (A'm), E'm/A'm ratio, myocardial precontraction time (PCT'm), myocardial contraction time (CT'm), and myocardial isovolumetric relaxation time (IVRT'm), E to E'm ratio were measured. RESULTS: In pulsed wave Doppler echocardiography, mitral late diastolic flow (A) velocity and E to E'm ratio were significantly higher (P = 0.02 and P = 0,017), E/A ratio was significantly lower (P = 0.008) and IVRT was significantly prolonged (P = 0.014) in patients with CD. In TDE, S'm, E'm, and E'm/A'm ratio were significantly lower, IVRT'm was longer (P = 0.009) from septal mitral annulus and S'm, E'm, E'm/A'm ratio were significantly lower, PCT'm, PCT/ET ratio, IVRT'm were longer, and MPI was higher from lateral mitral annulus in celiac group than controls. CONCLUSION: Our study confirms that patients with CD have impaired diastolic function. More importantly, we also demonstrated an impairment of myocardial systolic function in patients with CD by TDE. We recommend using TDE in addition to conventional echocardiography parameters for the cardiovascular risk assessment of patients with CD. PMID- 26997218 TI - Randomized controlled trial of cholestyramine and hydrotalcite to eliminate bile for capsule endoscopy. AB - BACKGROUND/AIMS: Bile is the main cause of poor bowel preparation for capsule endoscopy (CE). We aimed to determine whether cholestyramine and hydrotalcite can eliminate bile in the bowel. PATIENTS AND METHODS: Patients undergoing CE were randomized into two groups. Group A patients (n = 75) received 250 mL 20% mannitol and 1 L 0.9% saline orally at 20:00 hours on the day before and at 05:00 hours on the day of CE and 20 mL simethicone 30 min before CE. Group B patients (n = 73) were treated identically, except for taking oral cholestyramine and hydrotalcite, starting 3 days before CE. Greenish luminal contents were assessed by four tissue color bar segments using Color Area Statistics software. Bowel cleanliness was evaluated by visualized area percentage assessment of cleansing (AAC) score. RESULT: Bowel cleanliness (82.7% [62/75] vs 46.6% [34/73]; chi2 = 14.596, P = 0.000). and detected greenish luminal contents (20.0% [15/75] vs 8.2% [6/73]; chi2 = 4.217, P = 0.040) were significantly greater in Group A than in Group B. Greenish luminal contents in the two groups differed significantly in the captured small-bowel (t = -13.74, P = 0.000) segments and proximal small bowel (t = -0.7365, P = 0.000) segments, but not for the distal small-bowel (t = 0.552, P = 0.581) segments. CONCLUSIONS: Cholestyramine and hydrotalcite were ineffective in eliminating bile and improving small-bowel preparation. PMID- 26997219 TI - Adherence and treatment satisfaction in liver transplant recipients. AB - BACKGROUND/AIMS: Liver transplantation (LT) is a life-saving intervention for patients with liver failure. LT recipients' adherence to their therapeutic regimen is an essential element for graft survival. According to WHO, the impact of medication non-adherence in solid organ transplantation has shown to cost $15 100 million annually. The aim of the present study was to identify the factors that best predict medication adherence and to explore the relationship between treatment satisfaction and medication adherence in liver transplant recipients. PATIENTS AND METHODS: Adult liver transplant patients at King Abdulaziz Medical City were included in the study. Patients completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4) in addition to several socio-demographic and transplant related data. RESULTS: A total of 154 patients were included in the study and of these 59.7% were adherent. Older age was a significant predictor of adherence (P < 0.05). The mean treatment satisfaction score was 91.9 +/- 12.7 in Effectiveness, 80.0 +/- 25.9 in Side Effects, 83.5 +/- 15.7 in Convenience, and 94.6 +/- 8.6 in Global Satisfaction. Further analysis indicated that patients in the adherent group had reported significantly higher satisfaction scores than those in the non-adherent group (P < 0.05) in all treatment satisfaction domains: Effectiveness (94.4 +/- 10.4 vs. 88.6 +/- 14.8), Side Effects (83.9 +/- 22.0 vs. 74.2 +/- 30.1), Convenience (87.0 +/- 13.9 vs. 77.2 +/- 16.1), and Global Satisfaction (96.9 +/- 6.6 vs. 91.2 +/- 8.6). CONCLUSION: Older patients and those who were more satisfied with their treatment tend to have better adherence to the prescribed medications. Therefore, increasing patients' satisfaction with their treatment should be an integral element of future care plans designed to improve treatment outcomes in liver transplant recipients. PMID- 26997220 TI - Surface gene variants of hepatitis B Virus in Saudi Patients. AB - BACKGROUND/AIMS: Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. Surface (S) protein is the major HBV antigen that mediates virus attachment and entry and determines the virus subtype. Mutations in S gene, particularly in the "a" determinant, can influence virus detection by ELISA and may generate escape mutants. Since no records have documented the S gene mutations in HBV strains circulating in Saudi Arabia, the current study was designed to study sequence variation of S gene in strains circulating in Saudi Arabia and its correlation with clinical and risk factors. PATIENTS AND METHODS: A total of 123 HBV-infected patients were recruited for this study. Clinical and biochemical parameters, serological markers, and viral load were determined in all patients. The entire S gene sequence of samples with viral load exceeding 2000 IU/mL was retrieved and exploited in sequence and phylogenetic analysis. RESULTS: A total of 48 mutations (21 unique) were recorded in viral strains in Saudi Arabia, among which 24 (11 unique) changed their respective amino acids. Two amino acid changes were recorded in "a" determinant, including F130L and S135F with no evidence of the vaccine escape mutant G145R in any of the samples. No specific relationship was recognized between the mutation/amino acid change record of HBsAg in strains in Saudi Arabia and clinical or laboratory data. Phylogenetic analysis categorized HBV viral strains in Saudi Arabia as members of subgenotypes D1 and D3. CONCLUSION: The present report is the first that describes mutation analysis of HBsAg in strains in Saudi Arabia on both nucleotide and amino acid levels. Different substitutions, particularly in major hydrophilic region, may have a potential influence on disease diagnosis, vaccination strategy, and antiviral chemotherapy. PMID- 26997221 TI - Association of global DNA hypomethylation with clinicopathological variables in colonic tumors of Iraqi patients. AB - BACKGROUND/AIM: Colorectal cancer (CRC) ranks sixth among the most common 10 cancers in Iraq. It is a foremost public health dilemma and there is improved interest in understanding the fundamental principles of its molecular biology. DNA methylation in cancer has become the issue of passionate investigation. As compared with normal cells, the malignant cells show major disruptions in their DNA methylation patterns. We aimed to assess the association of global DNA hypomethylation in colonic adenomas and carcinomas of Iraqi patients, measured by immunohistochemistry of 5-methylcytosin, with different clinicopathological variables. PATIENTS AND METHODS: Thirty tissue paraffin blocks from patients with colorectal adenomas, 30 tissue paraffin blocks from patients with colorectal adenocarcinomas, and 30 samples of apparently normal colonic tissue taken from autopsy cases as a control group were included in the present study. From each block, two sections of 5 MUm thickness were taken, one section was stained with Hematoxylin and Eosin for revision of histopathological diagnosis and one section was immunohistochemically stained for 5-methylcytosine (5mC) and digitally analyzed by AperioImageScope software. RESULTS: The mean digital value of 5mC immunohistochemical expression was sequentially decreased during neoplastic progression from normal colonic tissue into adenoma and then to carcinoma. The mean digital value of 5mC expression was significantly lower in large size adenomas (>=1 cm), and those with severe dysplasia. Concerning carcinoma cases, 5mC expression was significantly lower in stage C2. CONCLUSIONS: The immunohistochemical evaluation of 5mC yields refined information on colorectal tumor biology in adenoma and carcinoma. Global DNA hypomethylation reflected by low immunohistochemical expression of 5-mC is associated with advanced colorectal adenomatous polyps suggesting that it is an early event in colorectal carcinogenesis. Also this hypomethylation can reflect bad prognosis of patients with colorectal cancer by its correlation to higher tumor stage. PMID- 26997222 TI - Utility of rectoscopy in the assessment of response to neoadjuvant treatment for locally advanced rectal cancer. AB - BACKGROUND/AIMS: The management of locally advanced rectal cancer has changed substantially over the last few decades with neoadjuvant chemoradiotherapy. The aim of the present study is to compare the results between neoadjuvant post treatment rectoscopy and the anatomopathological findings of the surgical specimen. PATIENTS AND METHODS: We conducted a prospective study of 67 patients with locally advanced adenocarcinoma of the rectum (stages II and III). Two groups were established: One with complete clinical response (cCR) and one without (non-cCR), based on the findings at rectoscopy. Assessment of tumor regression grade in the surgical specimen was determined using Mandard's tumor regression scale. RESULTS: Seventeen patients showed a cCR. Thirty-five biopsies were negative and 32 were positive for malignancy. All the cCR patients had a negative biopsy (P < 0.0001). All 32 positive biopsies revealed the presence of adenocarcinoma, and of the 35 negative biopsies, 18 had no malignancy and 17 were diagnosed with adenocarcinoma (P < 0.0001). Sixteen of the 17 cCR patients showed a complete pathological response and one patient showed the presence of adenocarcinoma. Of the 50 non-cCR patients 48 revealed the presence of adenocarcinoma and two had absence of malignancy. According to the Mandard classification, 16 of the 17 cCR patients were grade I and 1 grade II; 2 non-cCR patients were grade I, 7 grade II, 13 grade III, 19 grade IV, and 9 grade V. CONCLUSIONS: Endoscopic and histological findings could be determinants in the assessment of response to neoadjuvant treatment. PMID- 26997223 TI - Anatomical predilection of intestinal metaplasia based on 78,335 endoscopic cases. AB - BACKGROUND/AIMS: Gastric intestinal metaplasia (IM) is an important risk factor for intestinal-type gastric carcinoma, and successful treatment critically depends on its timely detection. In order to guide appropriate endoscopic surveillance, objective knowledge on the anatomical predilection of intestinal metaplasia development is urgently needed. MATERIALS AND METHODS: A total of 78,335 cases who underwent gastroduodenoscopy from 2008 to 2013 in Jiangsu and Anhui provinces in China, were studied. Demographic and clinical characteristics, as well as biopsy location and histological results, were analyzed. RESULTS: This study revealed that intestinal metaplasia incidence was 28.5% in angulus, 20.24% in lesser curvature of the antrum, and 25.48% in corpus; and all these were significantly higher than those observed in other sites (P < 0.01). Histological grading of intestinal metaplasia in the lesser curvature of the antrum and angulus was generally worse than the grading observed in the greater curvature of the antrum. For Helicobacter pylori-positive patients, acute inflammation was more severe in the lesser curvature of the antrum compared with the greater curvature. In the H. Pylori-negative group, both acute and chronic inflammations were more severe in the lesser curvature of the antrum. CONCLUSIONS: The angulus, lesser curvature in the antrum, and corpus are most prone to the development of intestinal metaplasia. Inflammation is most severe in the lesser curvature of the antrum, which corresponds to a higher predilection to develop intestinal metaplasia at this site. The lesser curvature of the antrum and corpus require the most attention during endoscopic biopsy surveillance. PMID- 26997224 TI - Study of biofilm formation in C57Bl/6J mice by clinical isolates of Helicobacter pylori. AB - BACKGROUND/AIM: Despite the significant number of studies on H. pylori pathogenesis, not much data has been published concerning its ability to form biofilm in the host stomach. This study aims to evaluate the potential of clinical isolates of H. pylori to form biofilm in C57BL/6J mice model. MATERIALS AND METHODS: Two strains of H. pylori were selected from a collection of clinical isolates; one (19B), an efficient biofilm producer and the other (4B), with weak biofilm-forming ability. Mice infected through gastric avages were examined after one and two weeks. Colonization was determined by CFU and urease activity; the anti-H. pylori IgA was measured by ELISA, and chronic infections were evaluated by histopathology. Bacterial communities within mucosal sections were studied by immunofluorescence and scanning electron microscopy (SEM). RESULTS: Successful infection was obtained by both test strains. Strain 19B with higher ability to form biofilm in vitro also showed a higher colonization rate in the mice stomach one week after infection. Difference (P < 0.05) in IgA titers was observed between the infected mice and the controls as well as between 19B and 4B infected mice, two weeks after the last challenge. Immunofluorescence and SEM results showed tightly colonizing H. pylori in stomach mucosal sections and in squamous and glandular epithelium. CONCLUSION: H. pylori is able to form biofilm in the mouse stomach and induce IgA production, reflecting the same potential as in humans. Firm attachment of coccoid form bacteria to host cells suggests the importance of this state in biofilm formation by H. pylori. Occurrence of biofilm in squamous and glandular epithelium of the mouse stomach proposes that H. pylori can all parts of the upper gastrointestinal tract. PMID- 26997226 TI - Discriminating complement-mediated acute transfusion reaction for type O+ red blood cells transfused into a B+ recipient with the complement hemolysis using human erythrocytes (CHUHE) assay. AB - BACKGROUND: A patient with B+ sickle cell disease received 3 units of red blood cells (RBCs) from two O+ donors and developed fever and hypotension after the first unit, consistent with an acute transfusion reaction (ATR). Anti-B titers in plasma from each O+ donor were markedly elevated and nondiscriminatory. In order to evaluate the potential for the transfused units to produce complement-mediated hemolysis of B+ RBCs, hemolytic complement testing was performed. STUDY DESIGN AND METHODS: Plasma from each donor was diluted in veronal buffer and incubated with B+ RBCs, and free hemoglobin was measured by spectrophotometer in the complement hemolysis using human erythrocytes (CHUHE) assay. Peptide inhibitor of complement C1 (PIC1) was used to confirm antibody-initiated complement pathway activation. RESULTS: A 96-fold difference (p = 0.014) in hemolysis was measured between plasma samples from the two O+ donors using the CHUHE assay. The extremely high degree of hemolysis produced by the one plasma was inhibited by PIC1 in a dose-dependent manner. CONCLUSION: These results indicate that hemolytic complement testing with the CHUHE assay can be used to assess the risk of antibody-initiated, complement-mediated hemolysis from a transfusion beyond what can be achieved with antibody titers alone. PMID- 26997227 TI - Measuring research success. AB - Defining successful research can be complex. For novice researchers, success may involve completing research projects and publishing in peer-reviewed journals, but for experienced researchers more complex measures of success come into play. Each researcher's reputation, future grant funding and career prospects depend on the success of each project, and the quality of the researcher's track record. PMID- 26997225 TI - Staphylococcal Nuclease and Tudor Domain Containing 1 (SND1 Protein) Promotes Hepatocarcinogenesis by Inhibiting Monoglyceride Lipase (MGLL). AB - Staphylococcal nuclease and tudor domain containing 1 (SND1) is overexpressed in multiple cancers, including hepatocellular carcinoma (HCC), and functions as an oncogene. This study was carried out to identify novel SND1-interacting proteins to better understand its molecular mechanism of action. SND1-interacting proteins were identified by a modified yeast two-hybrid assay. Protein-protein interaction was confirmed by co-immunoprecipitation analysis. Monoglyceride lipase (MGLL) expression was analyzed by quantitative RT-PCR, Western blot, and immunohistochemistry. MGLL-overexpressing clones were analyzed for cell proliferation and cell cycle analysis and in vivo tumorigenesis in nude mice. MGLL was identified as an SND1-interacting protein. Interaction of SND1 with MGLL resulted in ubiquitination and proteosomal degradation of MGLL. MGLL expression was detected in normal human hepatocytes and mouse liver, although it was undetected in human HCC cell lines. An inverse correlation between SND1 and MGLL levels was identified in a human HCC tissue microarray as well as in the TCGA database. Forced overexpression of MGLL in human HCC cells resulted in marked inhibition in cell proliferation with a significant delay in cell cycle progression and a marked decrease in tumor growth in nude mouse xenograft assays. MGLL overexpression inhibited Akt activation that is independent of enzymatic activity of MGLL and overexpression of a constitutively active Akt rescued cells from inhibition of proliferation and restored normal cell cycle progression. This study unravels a novel mechanism of SND1 function and identifies MGLL as a unique tumor suppressor for HCC. MGLL might function as a homeostatic regulator of Akt restraining its activation. PMID- 26997228 TI - Solving the context-process problem. PMID- 26997229 TI - Mixed-methods study to develop a patient complexity assessment instrument for district nurses. AB - BACKGROUND: There is increasing reference to complex patient needs in health care. However, little is known about how to measure patient complexity or the relationship between it and district nursing activity. AIM: To illustrate the use of group concept mapping (GCM) to conceptualise and develop items for a patient complexity assessment instrument to be used by district nurses. DISCUSSION: The first phase of this research used GCM conceptualisation and consensus methodology to identify items for a community-based patient complexity instrument. GCM helped to provide a conceptual understanding of community-based patient complexity through focused exploration of the term. RESULTS: indicated that a number of environmental, sociological, psychological, behavioural, physical and organisational factors needed to be included. This, in turn, showed that an existing taxonomy did not contain the relevant items. Consequently, amendments were made and a new instrument developed. CONCLUSION: GCM is a suitable consensus method for use in nursing theory and developing instruments. It proved successful in achieving consensus with no loss of participants' views. IMPLICATIONS FOR PRACTICE: GCM is a suitable method for nurses to use in research or practice development activities as it is based on a facilitative and engagement-led approach. PMID- 26997231 TI - Setting a research question, aim and objective. AB - AIM: To describe the development of a research question, aim and objective. BACKGROUND: The first steps of any study are developing the research question, aim and objective. Subsequent steps develop from these and they govern the researchers' choice of population, setting, data to be collected and time period for the study. Clear, succinctly posed research questions, aims and objectives are essential if studies are to be successful. DISCUSSION: Researchers developing their research questions, aims and objectives generally experience difficulties. They are often overwhelmed trying to convert what they see as a relevant issue from practice into research. This necessitates engaging with the relevant published literature and knowledgeable people. CONCLUSION: This paper identifies the issues to be considered when developing a research question, aim and objective. Understanding these considerations will enable researchers to effectively present their research question, aim and objective. IMPLICATIONS FOR PRACTICE: To conduct successful studies, researchers should develop clear research questions, aims and objectives. PMID- 26997230 TI - Validation of the professional practice environment scale in nurse educators in hospitals. AB - AIM: To report an assessment of the psychometric properties of the Professional Practice Environment (PPE) scale in a sample of Australian nurse educators in acute care hospitals. BACKGROUND: Although nurse educators are important in an enabling work environment, there has been no reported exploration of their satisfaction with work in acute care hospitals. DISCUSSION: The factor structure and internal consistency of the PPE scale were consistent with Erickson's eight factor model of the items, indicating the appropriateness of the scale as an assessment tool to measure the PPE of nurse educators. CONCLUSION: The PPE scale is useful for monitoring the work environment of nurse educators in clinical practice and the environmental effects influencing their recruitment, retention and job satisfaction. IMPLICATIONS FOR PRACTICE: This work may inform the development of integrated professional practice environments where the professional practice and workplace satisfaction of nurse educators are optimised, influencing safe, quality patient care. PMID- 26997232 TI - Protocol for a block randomised controlled trial of an intervention to improve heart failure care. AB - AIM: To describe the design of a randomised controlled trial conducted to evaluate a culturally tailored, nurse-led educational intervention. BACKGROUND: Self-care strategies are critical to improving health outcomes in heart failure. The family unit is crucial in collectivist cultures, but little is known about involving the family in the self-care of patients with heart failure. DISCUSSION: Involving the family in the self-care of heart failure is a novel approach. To the authors' knowledge, no one has evaluated it using a randomised controlled trial. CONCLUSION: A valid comparison of outcomes between the control group and the intervention group involved in the study was provided in this trial. The chosen design, randomised controlled trial, enabled the assessment of the intervention. IMPLICATIONS FOR PRACTICE: The application of a family self-care intervention in a collectivist culture was shown to improve clinical and quality outcomes of patients with heart failure. Considering the individual and the community needs is vital in improving these outcomes. PMID- 26997233 TI - Involving mental health service users in suicide-related research: a qualitative inquiry model. AB - AIM: To describe the research model developed and successfully deployed as part of a multi-method qualitative study investigating suicidal service-users' experiences of mental health nursing care. BACKGROUND: Quality mental health care is essential to limiting the occurrence and burden of suicide, however there is a lack of relevant research informing practice in this context. Research utilising first-person accounts of suicidality is of particular importance to expanding the existing evidence base. However, conducting ethical research to support this imperative is challenging. DISCUSSION: The model discussed here illustrates specific and more generally applicable principles for qualitative research regarding sensitive topics and involving potentially vulnerable service-users. CONCLUSION: Researching into mental health service users with first-person experience of suicidality requires stakeholder and institutional support, researcher competency, and participant recruitment, consent, confidentiality, support and protection. IMPLICATIONS: Research with service users into their experiences of sensitive issues such as suicidality can result in rich and valuable data, and may also provide positive experiences of collaboration and inclusivity. If challenges are not met, objectification and marginalisation of service-users may be reinforced, and limitations in the evidence base and service provision may be perpetuated. PMID- 26997234 TI - Lessons learned from recruiting nursing homes to a quantitative cross-sectional pilot study. AB - BACKGROUND: A growing older adult population is leading to increased admission rates to long-term care facilities such as nursing homes and residential care homes. Assisted healthcare services should be flexible, integrated, and responsive to older adults' needs. However, there is a limited body of empirical evidence because of the recruitment challenges in these settings. AIM: To describe the barriers and challenges faced in recruiting to a recent pilot study, consider previously implemented and proposed recruitment strategies, and propose a new multi-method approach to maximising recruitment of care homes. DISCUSSION: The proposed multi-method approach harnesses key recruitment strategies previously highlighted as effective in navigating the many challenges and barriers that are likely to be encountered, such as mistrust, scepticism and concerns about disruption to routines. This includes making strategic use of existing personal and professional connections within the research team, engaging with care homes that have previously engaged with the research process, forming relationships of trust, and employing a range of incentives. CONCLUSION: Implementing carefully planned recruitment strategies is likely to improve relationships between nursing homes and researchers. As a consequence, recruitment can be augmented which can enable the production of rigorous evidence required for achieving effective nursing practice and patient wellbeing. IMPLICATIONS FOR PRACTICE: Boosting recruitment rates is crucial in helping to build new and less biased research evidence and for informing and underpinning all forms of evidence-based practice. The lessons learned from our pilot and the review of the literature highlight these issues and better enable investigators to access research settings that commonly possess many complex recruitment barriers and challenges. PMID- 26997238 TI - Control of microbiological corrosion on carbon steel with sodium hypochlorite and biopolymer. AB - In the present work, the interaction of a mixture of a biocide, sodium hypochlorite (NaClO), and a biopolymer, xanthan, with carbon steel coupons exposed to seawater in a turbulent flow regime was studied. The cell concentrations, corrosion rates, biomasses, and exopolysaccharides (EPSs) produced on the coupon surfaces with the various treatments were quantified. The corrosion products were evaluated using X-ray diffraction (XRD), and the surfaces of steels were analysed by scanning electron microscopy (SEM). The results indicated that xanthan and the hypochlorite-xanthan mixture reduced the corrosion rate of steel. PMID- 26997239 TI - A study on the adsorption of methylene blue onto gum ghatti/TiO2 nanoparticles based hydrogel nanocomposite. AB - The objective of this work was to study the isotherm and kinetic models for the adsorption of methylene blue (MB) onto a TiO2 nanoparticle (TiO2NP)-containing hydrogel nanocomposite (HNC) of polyacrylamide-grafted gum ghatti (PAAm-g-Gg). The grafting of PAAm onto Gg was conducted using N,N'-methylene-bis-acrylamide (MBA) as a crosslinker, and different weight percentages of TiO2NPs were incorporated into the hydrogel matrix during the grafting reaction. The graft co polymerization and the formation of the HNC were confirmed using FTIR, XRD, BET, SEM, TEM and EDS analyses. The adsorption of MB was studied in batch mode and it was found to be highly dependent on solution pH, ionic strength temperature and adsorbent loading. The MB-adsorption process followed the pseudo-second-order rate model and Langmuir adsorption isotherm with a maximum adsorption capacity of 1305.5mgg(-1). Thermodynamic studies revealed that the adsorption of MB onto the HNC surface was spontaneous, endothermic and through a process of physisorption. The results also showed that the HNC was much more effective for the adsorption of cationic dyes than anionic dyes, and it retained its original adsorption capacity for five successive cycles of adsorption-desorption. In conclusion, the hydrogel nanocomposite showed huge potential for remediating industrial wastewater polluted by toxic cationic dyes. PMID- 26997240 TI - Oropharyngeal Crowding Closely Relates to Aggravation of OSA. AB - BACKGROUND: Obesity is known to be an important risk factor for OSA; however, OSA can also be seen in nonobese patients with a small maxilla and/or mandible as well as in all obese patients with such features. Thus, we hypothesized that regional factors, oropharyngeal crowding associated with fat deposition, and maxillomandibular enclosure size closely related to the severity of OSA. METHODS: A total of 703 male Japanese subjects were enrolled; theywere classified into obese (BMI >= 30 kg/m(2); n = 158) and nonobese (BMI < 30 kg/m(2); n = 545) groups. Using lateral cephalometric analysis, we measured the tongue size (TG), lower face cage (LFC), and TG/LFC ratio (ie, oropharyngeal crowding) to evaluate the state of upper airway crowding. The correlations between these cephalometric measurements and BMI, age, and the apnea-hypopnea index (AHI) were evaluated. RESULTS: In obese subjects, the TG/LFC ratio, BMI, and TG positively correlated with AHI, whereas, in nonobese subjects, age, BMI, and TG/LFC significantly correlated with AHI. Subsequent stepwise multiple linear regression analysis revealed that the variables associated with AHI differed between obese and nonobese OSA subjects, although BMI and TG/LFC were significantly associated with AHI in both groups. In particular, the contribution of TG/LFC to AHI was larger than that of BMI in the obese group. CONCLUSIONS: Oropharyngeal crowding is a local anatomic factor that independently relates to the severity of OSA in both obese and nonobese patients; the more crowded the upper airway, the more severe the OSA. PMID- 26997242 TI - High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis. AB - OBJECTIVE: Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis. METHODS: Sera from the Oslo University Hospital SSc cohort (n = 298) and healthy control subjects (n = 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53 ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff. RESULTS: High serum CCL18 was identified in 35% (105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3% and 4.7%; P = .016), as did the annual progression rate of lung fibrosis (0.9% [SD, 2.9] and 0.2% [SD, 1.9]). Highest rates of annual FVC decline > 10% (21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10% (OR, 1.1; 95% CI, 1.01-1.11) and FVC < 70% at follow-up (OR, 3.1; 95% CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85% and 74%, compared with 97% and 89%, respectively; P = .001). CONCLUSIONS: The results from this prospective cohort reinforce the notion that high CCL18 may serve as a marker for early identification of progressive ILD in SSc. PMID- 26997241 TI - Early Mobilization and Rehabilitation of Patients Who Are Critically Ill. AB - Neuromuscular disorders are increasingly recognized as a cause of both short- and long-term physical morbidity in survivors of critical illness. This recognition has given rise to research aimed at better understanding the risk factors and mechanisms associated with neuromuscular dysfunction and physical impairment associated with critical illness, as well as possible interventions to prevent or treat these issues. Among potential risk factors, bed rest is an important modifiable risk factor. Early mobilization and rehabilitation of patients who are critically ill may help prevent or mitigate the sequelae of bed rest and improve patient outcomes. Research studies and quality improvement projects have demonstrated that early mobilization and rehabilitation are safe and feasible in patients who are critically ill, with potential benefits including improved physical functioning and decreased duration of mechanical ventilation, intensive care, and hospital stay. Despite these findings, early mobilization and rehabilitation are still uncommon in routine clinical practice, with many perceived barriers. This review summarizes potential risk factors for neuromuscular dysfunction and physical impairment associated with critical illness, highlights the potential role of early mobilization and rehabilitation in improving patient outcomes, and discusses some of the commonly perceived barriers to early mobilization and strategies for overcoming them. PMID- 26997245 TI - Flexible Hall sensors based on graphene. AB - The excellent electronic and mechanical properties of graphene provide a perfect basis for high performance flexible electronic and sensor devices. Here, we present the fabrication and characterization of flexible graphene based Hall sensors. The Hall sensors are fabricated on 50 MUm thick flexible Kapton foil using large scale graphene grown by chemical vapor deposition technique on copper foil. Voltage and current normalized sensitivities of up to 0.096 V VT(-1) and 79 V AT(-1) were measured, respectively. These values are comparable to the sensitivity of rigid silicon based Hall sensors and are the highest values reported so far for any flexible Hall sensor devices. The sensitivity of the Hall sensor shows no degradation after being bent to a minimum radius of 4 mm, which corresponds to a tensile strain of 0.6%, and after 1000 bending cycles to a radius of 5 mm. PMID- 26997244 TI - Kinds versus continua: a review of psychometric approaches to uncover the structure of psychiatric constructs. AB - The question of whether psychopathology constructs are discrete kinds or continuous dimensions represents an important issue in clinical psychology and psychiatry. The present paper reviews psychometric modelling approaches that can be used to investigate this question through the application of statistical models. The relation between constructs and indicator variables in models with categorical and continuous latent variables is discussed, as are techniques specifically designed to address the distinction between latent categories as opposed to continua (taxometrics). In addition, we examine latent variable models that allow latent structures to have both continuous and categorical characteristics, such as factor mixture models and grade-of-membership models. Finally, we discuss recent alternative approaches based on network analysis and dynamical systems theory, which entail that the structure of constructs may be continuous for some individuals but categorical for others. Our evaluation of the psychometric literature shows that the kinds-continua distinction is considerably more subtle than is often presupposed in research; in particular, the hypotheses of kinds and continua are not mutually exclusive or exhaustive. We discuss opportunities to go beyond current research on the issue by using dynamical systems models, intra-individual time series and experimental manipulations. PMID- 26997243 TI - Effect of Continuous Positive Airway Pressure on Cardiovascular Biomarkers: The Sleep Apnea Stress Randomized Controlled Trial. AB - BACKGROUND: Although existing research highlights the relationship of OSA and cardiovascular disease, the effect of OSA treatment on cardiovascular biomarkers remains unclear. We evaluated the effect of OSA treatment on oxidative stress/inflammation measures. METHODS: We conducted a parallel, randomized controlled trial in moderate to severe OSA (apnea-hypopnea index >= 15) patients to examine effects of 2-month CPAP vs sham-CPAP on the primary outcome of oxidative stress/inflammation (F2-isoprostanes: ng/mg) and myeloperoxidase: pmol/L) and secondary oxidative stress measures. Exploratory secondary analyses included vascular and systemic inflammation markers. Linear models adjusted for baseline values examined effect of CPAP on biomarker change (least squares means, 95% CI) including secondary stratified analyses examining CPAP adherence and degree of hypoxia. RESULTS: Of 153 participants, 76 were randomized to CPAP and 77 to sham-CPAP. In an intent-to-treat analyses, no significant change was observed in the sham and CPAP groups respectively: F2-isoprostanes (-0.02 [-0.12 to 0.10] vs -0.08 [-0.18 to 0.03]) or myeloperoxidase (-3.33 [-17.02 to 10.37] vs -5.15 [-18.65 to 8.35]), nor other oxidative markers; findings that persisted in analyses stratified by adherence and hypoxia. Exploratory analyses revealed percentage reduction of soluble IL-6 receptor (ng/mL) levels (-0.04 [-0.08 to 0.01] vs 0.02 [-0.02 to 0.06], P = .019) and augmentation index (%) (-6.49 [-9.32 to -3.65] vs 0.44 [-2.22 to 3.10], P < .001) with CPAP compared with sham, respectively. CONCLUSIONS: In moderate to severe OSA, 2-month CPAP vs sham did not reduce oxidative stress despite consideration of a broad range of measures, positive airway pressure adherence, and hypoxia burden. These findings suggest that nonoxidative stress pathways primarily modulate OSA-related cardiovascular consequences. TRIAL REGISTRATION: ClinicalTrials.govNCT00607893. PMID- 26997246 TI - How do neuroanatomical changes in individuals with chronic pain result in the constant perception of pain? AB - Since the advent of anatomical brain imaging analysis techniques, numerous reports have shown altered regional brain anatomy in individuals with various chronic pain conditions. While early reports of increased regional brain volumes in taxi drivers and pianists were simply interpreted as responses to excessive use, the mechanisms responsible for anatomical changes associated with chronic pain are not so straightforward. The main aim of this paper is to explore the potential underlying cellular changes responsible for change in gross brain anatomy in individuals with chronic pain, in particular pain following nervous system damage. Determining the basis of these changes may provide a platform for development of targeted, personalized and ultimately more effective treatment regimens. PMID- 26997250 TI - Understanding the tautomerism in azacalixphyrins. AB - Understanding the chemical nature and spectroscopic signatures of a new class of organic molecules remains a strong challenge. Azacalixphyrin, the first member of a family of strongly aromatic macrocycles absorbing in the near infrared domain, can exist in several tautomeric forms. Here, we use DFT calculations and NMR measurements to propose the first in-depth investigation of proton exchanges occurring in two forms of azacalixphyrins (non-protonated and protonated). Our results reveal, on the one hand, a very effective solvent-assisted tautomerism in the non-protonated form whereas the intramolecular proton transfer is less probable, and, on the other hand, the presence of a mixture of almost isoenergetic tautomers differing in both their aromaticity and absorption profiles. This clearly indicates that smartly-designed chemical substitutions could alter the relative weights of the different tautomers, and consequently tune the optical signatures of these new macrocycles in a versatile and efficient way. For the protonated form, rotations of the NH2 groups take place rather than the chemical exchange. PMID- 26997248 TI - Factors associated with the use of elective single-embryo transfer and pregnancy outcomes in the United States, 2004-2012. AB - OBJECTIVE: To evaluate factors associated with elective single-embryo transfer (eSET) utilization and its effect on assisted reproductive technology outcomes in the United States. DESIGN: Historical cohort. SETTING: Not applicable. PATIENT(S): Fresh IVF cycles of women aged 18-37 years using autologous oocytes with either one (SET) or two (double-embryo transfer [DET]) embryos transferred and reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2004 and 2012. Cycles were categorized into four groups with ([+]) or without ([-]) supernumerary embryos cryopreserved. The SET group with embryos cryopreserved was designated as eSET. INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): The likelihood of eSET utilization, live birth, and singleton non-low birth weight term live birth, modeled using logistic regression. Presented as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULT(S): The study included 263,375 cycles (21,917 SET[ ]cryopreservation, 20,996 SET[+]cryopreservation, 103,371 DET[-]cryopreservation, and 117,091 DET[+]cryopreservation). The utilization of eSET (SET[+]cryopreservation) increased from 1.8% in 2004 to 14.9% in 2012 (aOR 7.66, 95% CI 6.87-8.53) and was more likely with assisted reproductive technology insurance coverage (aOR 1.60, 95% CI 1.54-1.66), Asian race (aOR 1.26, 95% CI 1.20-1.33), uterine factor diagnosis (aOR 1.48, 95% CI 1.37-1.59), retrieval of >=16 oocytes (aOR 2.85, 95% CI 2.55-3.19), and the transfer of day 5-6 embryos (aOR 4.23, 95% CI 4.06-4.40); eSET was less likely in women aged 35-37 years (aOR 0.76, 95% CI 0.73-0.80). Compared with DET cycles, the likelihood of the ideal outcome, term non-low birth weight singleton live birth, was increased 45%-52% with eSET. CONCLUSION(S): Expanding insurance coverage for IVF would facilitate the broader use of eSET and may reduce the morbidity and healthcare costs associated with multiple pregnancies. PMID- 26997247 TI - Cajal bodies are linked to genome conformation. AB - The mechanisms underlying nuclear body (NB) formation and their contribution to genome function are unknown. Here we examined the non-random positioning of Cajal bodies (CBs), major NBs involved in spliceosomal snRNP assembly and their role in genome organization. CBs are predominantly located at the periphery of chromosome territories at a multi-chromosome interface. Genome-wide chromosome conformation capture analysis (4C-seq) using CB-interacting loci revealed that CB-associated regions are enriched with highly expressed histone genes and U small nuclear or nucleolar RNA (sn/snoRNA) loci that form intra- and inter-chromosomal clusters. In particular, we observed a number of CB-dependent gene-positioning events on chromosome 1. RNAi-mediated disassembly of CBs disrupts the CB-targeting gene clusters and suppresses the expression of U sn/snoRNA and histone genes. This loss of spliceosomal snRNP production results in increased splicing noise, even in CB-distal regions. Therefore, we conclude that CBs contribute to genome organization with global effects on gene expression and RNA splicing fidelity. PMID- 26997249 TI - Increasing serum 25-hydroxyvitamin D is associated with reduced odds of long menstrual cycles in a cross-sectional study of African American women. AB - OBJECTIVE: To examine the association between serum 25-hydroxyvitamin D [25(OH)D] and menstrual cycle length and regularity. DESIGN: Community-based, cross sectional study of serum 25(OH)D (adjusted for seasonal differences in timing of blood draw) and menstrual cycle length. Women aged 23-34 years reported their gynecologic history. Menstrual cycles were described with four independent categories (normal, short, long, irregular). We used polytomous logistic regression to estimate the association between a doubling of seasonally adjusted 25(OH)D and the odds of each cycle category. SETTING: Not applicable. PATIENT(S): A total of 1,102 African American women. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Self-reported menstrual cycle length over the previous 12 months, excluding women who were using cycle-regulating medications over the entire year. Women who reported that their cycles were "too irregular to estimate" were classified as having irregular cycles. A typical cycle length of <27 days was considered "short," >34 days was "long," and 27-34 days was "normal." RESULT(S): The median 25(OH)D level was 14.7 ng/mL (interquartile range, 10.9-19.6 ng/mL). A doubling of 25(OH)D was associated with half the odds of having long menstrual cycles: adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.32-0.89. 25-Hydroxyvitamin D was not associated with the occurrence of short (aOR 1.03, 95% CI 0.82-1.29) or irregular (aOR 1.46, 95% CI 0.88-2.41) menstrual cycles. Results were robust to several sensitivity analyses. CONCLUSION(S): These findings suggest that vitamin D status may influence the menstrual cycle and play a role in ovarian function. Further investigation of 25(OH)D and ovarian hormones, and prospective studies of 25(OH)D and cycle length, are needed. PMID- 26997251 TI - Harnessing the Versatility of Continuous-Flow Processes: Selective and Efficient Reactions. AB - There is a great need for effective transformations and a broad range of novel chemical entities. Continuous-flow (CF) approaches are of considerable current interest: highly efficient and selective reactions can be performed in CF reactors. The reaction setup of CF reactors offers a wide variety of possible points where versatility can be introduced. This article presents a number of selective and highly efficient gas-liquid-solid and liquid-solid reactions involving a range of reagents and immobilized catalysts. Enantioselective transformations through catalytic hydrogenation and organocatalytic reactions are included, and isotopically labelled compounds and pharmaceutically relevant 1,2,3 triazoles are synthesized in CF reactors. Importantly, the catalyst bed can be changed to a solid-phase peptide synthesis resin, with which peptide synthesis can be performed with the utilization of only 1.5 equivalents of the amino acid. PMID- 26997252 TI - Colorimetric Detection of Escherichia coli Based on the Enzyme-Induced Metallization of Gold Nanorods. AB - A novel enzyme-induced metallization colorimetric assay is developed to monitor and measure beta-galactosidase (beta-gal) activity, and is further employed for colorimetric bacteriophage (phage)-enabled detection of Escherichia coli (E. coli). This assay relies on enzymatic reaction-induced silver deposition on the surface of gold nanorods (AuNRs). In the presence of beta-gal, the substrate p aminophenyl beta-d-galactopyranoside is hydrolyzed to produce p-aminophenol (PAP). Reduction of silver ions by PAP generates a silver shell on the surface of AuNRs, resulting in the blue shift of the longitudinal localized surface plasmon resonance peak and multicolor changes of the detection solution from light green to orange-red. Under optimized conditions, the detection limit for beta-gal is 128 pM, which is lower than the conventional colorimetric assay. Additionally, the assay has a broader dynamic range for beta-gal detection. The specificity of this assay for the detection of beta-gal is demonstrated against several protein competitors. Additionally, this technique is successfully applied to detect E. coli bacteria cells in combination with bacteriophage infection. Due to the simplicity and short incubation time of this enzyme-induced metallization colorimetric method, the assay is well suited for the detection of bacteria in low-resource settings. PMID- 26997253 TI - Prevalence of CTX-M resistance marker and integrons among Escherichia coli and Klebsiella pneumoniae isolates of clinical origin. AB - Bacterial pathogens producing CTX-M beta-lactamases are emerging around the world as a source of resistance to oxyimino cephalosporins such as cefotaxime. In this study, we have investigated the prevalence of blaCTX-M genes among clinical isolates of Escherichia coli and Klebsiella pneumoniae. Of the double-disk synergy test-positive E. coli (n = 94) and Kl. pneumoniae (n = 73) strains isolated during the study period, 41 (44.08%) E. coli and 32 (43.24%) Kl. pneumoniae isolates were found to be positive for blaCTX-M genes. Twenty-two integrons (13 for E. coli and 9 for Kl. pneumoniae) were detected whose sizes ranged from 600 bp to 1.5 kb. All these integrons were found to be of Class1 type and were invariably PCR positive for int1 and sul1 genes. Marker transfer experiments demonstrated plasmid-mediated transfer of cefotaxime and ceftazidime resistance markers. In addition, analysis of the enterobacterial repetitive intergenic consensus (ERIC)-PCR typing of the blaCTX-M -carrying isolates showed that they were genetically diverse and heterogeneous suggesting that multiple subtypes of the species were involved in infection. SIGNIFICANCE AND IMPACT OF THE STUDY: A high frequency of blaCTX-M -resistant marker has been found in Escherichia coli and Klebsiella pneumoniae isolates of clinical origin. Analysis of the ERIC-PCR typing of the blaCTX-M -carrying isolates showed that they were genetically diverse and heterogeneous suggesting that multiple subtypes of the species were involved in infection. PMID- 26997254 TI - Spatial-temporal variation, possible source and ecological risk of PCBs in sediments from Songhua River, China: Effects of PCB elimination policy and reverse management framework. AB - The spatial variation, possible sources and ecological risk of polychlorinated biphenyls (PCBs) in the sediment from the Songhua River, China were investigated and evaluated in this paper. The total concentration of PCBs ranged from 0.59 to 12.38ng/gdw, with a mean value of 3.82ng/gdw. The seven indicators of PCB concentrations are significantly correlated with the total PCB concentrations (R=0.950, p=0.000). The temporal trend of PCBs in sediments showed that the total PCBs in the Songhua River have decreased since 2008. Point source pollution, discharge of historical usage and industrial sewage, and emissions of unintentionally produced PCBs were the predominant sources in sediment. A risk assessment indicated that most of the sampling sites in the sediment were at low potential ecological risk. The apparent decrease of PCBs in the sediment appeared after the China National Coordination Group for Implementation of the Stockholm Convention was established. A conceptual reverse management framework for PCBs and other organic pollutants was established in this study. PMID- 26997255 TI - FTIR spectroscopy supported by statistical techniques for the structural characterization of plastic debris in the marine environment: Application to monitoring studies. AB - We inserted 190 FTIR spectra of plastic samples in a digital database and submitted it to Independent Component Analysis (ICA) to extract the "pure" plastic polymers present. These identified plastics were polypropylene (PP), high density polyethylene (HDPE), low density polyethylene (LDPE), high density polyethylene terephthalate (HDPET), low density polyethylene terephthalate (LDPET), polystyrene (PS), Nylon (NL), polyethylene oxide (OPE), and Teflon (TEF) and they were used to establish the similarity with unknown plastics using the correlation coefficient (r), and the crosscorrelation function (CC). For samples with r<0.8 we determined the Mahalanobis Distance (MD) as additional tool of identification. For instance, for the four plastic fragments found in the Carretta carretta, one plastic sample was assigned to OPE due to its r=0.87; for all the other three plastic samples, due to the r values ranging between 0.83 and0.70, the support of MD suggested LDPET and OPE as co-polymer constituents. PMID- 26997256 TI - Limited impact of fibromodulin deficiency on the development of experimental skin fibrosis. AB - Excessive production of collagen is the hallmark of fatal diseases of fibrosis such as systemic sclerosis. Overexpression of the proteoglycan fibromodulin (FMOD) has been associated with improved wound healing and scarless repair. In this study, we have investigated the consequences of FMOD deficiency on the development of experimental skin fibrosis. Using immunohistochemistry, we identified FMOD in both human and murine fibrotic skin. In the bleomycin model of skin fibrosis, FMOD(-/-) mice developed skin fibrosis to a similar degree compared to FMOD(+/+) mice. Analysis of skin ultrastructure using transmission electron microscopy revealed a significant reduction in collagen fibril diameter in FMOD(-/-) but not FMOD(+/+) mice following fibrosis. We conclude that the impact of FMOD deficiency on the development of experimental skin fibrosis is limited. PMID- 26997258 TI - Effects of pulsed light treatments and pectin edible coatings on the quality of fresh-cut apples: a hurdle technology approach. AB - BACKGROUND: Pulsed light (PL) treatments stand as an alternative for the shelf life extension of fresh-cut products. The antimicrobial effects of PL are well known; however, its influence on quality attributes needs to be assessed. This study was aimed at evaluating the application of PL treatments in combination with pectin-based edible coatings enriched with dietary fiber for the preservation of fresh-cut apples. RESULTS: Dipping of fresh-cut apples in ascorbic acid/calcium chloride solution prior to pectin coating and PL treatments was effective to minimize browning and softening of apple surfaces. Incorporation of fiber in the pectin coating did not cause any change in microbial loads and sensory acceptability of apple cubes. Pectin-coated PL-treated apple pieces exhibited significantly higher antioxidant activity values than fresh and PL control samples. At the end of storage, the combination of both treatments resulted in an almost 2 log CFU g-1 reduction of microbial counts. Sensory attribute scores did not fall below the rejection limit throughout 14 days, although the presence of off-odors limited the acceptability of the pectin-coated samples. CONCLUSION: The results demonstrate that PL treatments applied to pectin coated fresh-cut apples may be used to maintain quality attributes, thus conferring prebiotic potential and extending the shelf-life of the product. (c) 2016 Society of Chemical Industry. PMID- 26997257 TI - Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia. AB - Therapeutic hypothermia (HT) is standard care for moderate and severe neonatal hypoxic-ischaemic encephalopathy (HIE), the leading cause of permanent brain injury in term newborns. However, the optimal temperature for HT is still unknown, and few preclinical studies have compared multiple HT treatment temperatures. Additionally, HT may not benefit infants with severe encephalopathy. In a neonatal rat model of unilateral hypoxia-ischaemia (HI), the effect of five different HT temperatures was investigated after either moderate or severe injury. At postnatal-day seven, rat pups underwent moderate or severe HI followed by 5 h at normothermia (37 degrees C), or one of five HT temperatures: 33.5 degrees C, 32 degrees C, 30 degrees C, 26 degrees C, and 18 degrees C. One week after treatment, neuropathological analysis of hemispheric and hippocampal area loss, and CA1 hippocampal pyramidal neuron count, was performed. After moderate injury, a significant reduction in hemispheric and hippocampal loss on the injured side, and preservation of CA1 pyramidal neurons, was seen in the 33.5 degrees C, 32 degrees C, and 30 degrees C groups. Cooling below 33.5 degrees C did not provide additional neuroprotection. Regardless of treatment temperature, HT was not neuroprotective in the severe HI model. Based on these findings, and previous experience translating preclinical studies into clinical application, we propose that milder cooling should be considered for future clinical trials. PMID- 26997259 TI - The IL6R gene polymorphisms are associated with sIL-6R, IgE and lung function in Chinese patients with asthma. AB - BACKGROUND: sIL-6R is involved in a variety of inflammatory diseases. The present study analyzed the potential associations between two IL6R gene polymorphisms (rs2228145 and rs12083537) and asthma in a Han Chinese population. METHODS: A cohort of 394 patients and 395 healthy controls were genotyped to detect the two polymorphisms using SNaPshot. In 66 asthma patients and 49 controls, peripheral eosinophil and serum immunoglobulin E (IgE) levels were determined using a routine blood test, and sIL-6R levels were measured by ELISA. RESULTS: No statistically significant differences were detected between the patients and controls in the distribution of the two independent IL6R polymorphisms (p>0.05). However, rs2228145 C and rs12083537 G were significantly associated with decreased lung function in patients with asthma; the rs2228145 A-C variant was also associated with increased sIL-6R and IgE levels. In addition, sIL-6R levels were positively associated with IgE and inversely associated with lung function in patients with asthma. CONCLUSIONS: Our results provide evidence that rs2228145 C and rs12083537 G are associated with poor lung function in patients with asthma. Furthermore, the rs2228145 A-C variant is associated with levels of sIL 6R and IgE. PMID- 26997261 TI - Activity cycles and foraging behaviors of free-ranging sidewinder rattlesnakes (Crotalus cerastes): the ontogeny of hunting in a precocial vertebrate. AB - Predators often employ a complex series of behaviors to overcome antipredator defenses and effectively capture prey. Although hunting behaviors can improve with age and experience, many precocial species are necessarily effective predators from birth. Additionally, many predators experience innate ontogenetic shifts in predatory strategies as they grow, allowing them to adapt to prey more appropriate for their increased size and energetic needs. Understanding how the relative roles of innate age-specific adaptation and learning have evolved requires information on how predation behavior develops in situ, in free-ranging predators. However, most of the research on the ontogeny of predation behavior is based on laboratory studies of captive animals, largely due to the difficulty of following newborn individuals in nature. Here, we take advantage of the unique tracks left by juveniles of a precocial viperid, the sidewinder rattlesnake (Crotalus cerastes), which we used to follow free-ranging snakes in the field. We recorded details of their ambush hunting behavior, and compared the behaviors of these juveniles to adult snakes that we monitored in the field via radio telemetry. Although juvenile and adult behaviors were similar in most respects, we did find that adults chose more effective ambush sites, which may be due to their increased experience. We also found that juveniles (but typically not adults) perform periodic tail undulations while in ambush, and that juveniles displayed slightly different activity cycles. Both of these latter differences are likely the result of age-specific adaptations for juveniles' greater reliance on lizards versus small mammals as prey. We also compared the general predatory behavior of sidewinders to that of other species in the genus Crotalus. These findings will provide important baseline field information for more detailed empirical research on the ontogeny of predation behavior in precocial vertebrates. PMID- 26997260 TI - PELP1: Structure, biological function and clinical significance. AB - Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors. Notably, the PELP1 protein has a histone-binding domain, recognizes histone modifications and interacts with several chromatin-modifying complexes. PELP1 serves as a substrate of multitude of kinases, and phosphorylation regulates its functions in various complexes. Further, PELP1 plays essential roles in several pathways including hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response. PELP1 expression is upregulated in several cancers, its deregulation contributes to therapy resistance, and it is a prognostic biomarker for breast cancer survival. Recent evidence suggests that PELP1 represents a novel therapeutic target for many hormonal cancers. In this review, we summarized the emerging biological properties and functions of PELP1. PMID- 26997262 TI - Audit of anesthetic trainees' 'hands-on' operating room experience in an Australian tertiary children's hospital. AB - BACKGROUND: There are no internationally accepted guidelines about what constitutes adequate clinical exposure during pediatric anesthetic training. In Australia, no data have been published on the level of experience obtained by anesthetic trainees in pediatric anesthesia. There is, however, a new ANZCA (Australian and New Zealand College of Anaesthetists) curriculum that quantifies new training requirements. AIM: To quantify our trainees' exposure to clinical work in order to assess compliance with new curriculum and to provide other institutions with a benchmark for pediatric anesthetic training. METHODS: We performed a prospective audit to estimate and quantify our anesthetic registrars' exposure to pediatric anesthesia during their 6-month rotation at our institution, a tertiary pediatric hospital in Perth, Western Australia. RESULTS: Our data suggest that trainees at our institution will achieve the new ANZCA training standards comfortably, in terms of the required volume and breadth of exposure. Experience, however, of some advanced pediatric anesthetic procedures appears limited. CONCLUSIONS: Experience gained at our hospital easily meets the new College requirements. Experience of fiber-optic intubation and regional blocks would appear insufficient to develop sufficient skills or confidence. The study provides other institutions with information to benchmark against their own trainee experience. PMID- 26997263 TI - Erratum: Individualized strategies to target specific mechanisms of disease in malignant melanoma patients displaying unique mutational signatures. PMID- 26997264 TI - Reply. PMID- 26997265 TI - Structural Model of the Extracellular Assembly of the TCR-CD3 Complex. AB - Antigen recognition of peptide-major histocompatibility complexes (pMHCs) by T cells, a key step in initiating adaptive immune responses, is performed by the T cell receptor (TCR) bound to CD3 heterodimers. However, the biophysical basis of the transmission of TCR-CD3 extracellular interaction into a productive intracellular signaling sequence remains incomplete. Here we used nuclear magnetic resonance (NMR) spectroscopy combined with mutational analysis and computational docking to derive a structural model of the extracellular TCR-CD3 assembly. In the inactivated state, CD3gammaepsilon interacts with the helix 3 and helix 4-F strand regions of the TCR Cbeta subunit, whereas CD3deltaepsilon interacts with the F and C strand regions of the TCR Calpha subunit in this model, placing the CD3 subunits on opposing sides of the TCR. This work identifies the molecular contacts between the TCR and CD3 subunits, identifying a physical basis for transmitting an activating signal through the complex. PMID- 26997266 TI - CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling. AB - Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub) is assembled by the linear ubiquitin assembly complex (LUBAC), and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation. PMID- 26997267 TI - Chemokine Signaling Enhances CD36 Responsiveness toward Oxidized Low-Density Lipoproteins and Accelerates Foam Cell Formation. AB - Excessive uptake of oxidized low-density lipoproteins (oxLDL) by macrophages is a fundamental characteristic of atherosclerosis. However, signals regulating the engagement of these ligands remain elusive. Using single-molecule imaging, we discovered a mechanism whereby chemokine signaling enhanced binding of oxLDL to the scavenger receptor, CD36. By activating the Rap1-GTPase, chemokines promoted integrin-mediated adhesion of macrophages to the substratum. As a result, cells exhibited pronounced remodeling of the cortical actin cytoskeleton that increased CD36 clustering. Remarkably, CD36 clusters formed predominantly within actin-poor regions of the cortex, and these regions were primed to engage oxLDL. In accordance with enhanced ligand engagement, prolonged exposure of macrophages to chemokines amplified the accumulation of esterified cholesterol, thereby accentuating the foam cell phenotype. These findings imply that the activation of integrins by chemokine signaling exerts feedforward control over receptor clustering and effectively alters the threshold for cells to engage ligands. PMID- 26997268 TI - Assembly of an Evolutionarily Conserved Alternative Proteasome Isoform in Human Cells. AB - Targeted intracellular protein degradation in eukaryotes is largely mediated by the proteasome. Here, we report the formation of an alternative proteasome isoform in human cells, previously found only in budding yeast, that bears an altered subunit arrangement in the outer ring of the proteasome core particle. These proteasomes result from incorporation of an additional alpha4 (PSMA7) subunit in the position normally occupied by alpha3 (PSMA4). Assembly of "alpha4 alpha4" proteasomes depends on the relative cellular levels of alpha4 and alpha3 and on the proteasome assembly chaperone PAC3. The oncogenic tyrosine kinases ABL and ARG and the tumor suppressor BRCA1 regulate cellular alpha4 levels and formation of alpha4-alpha4 proteasomes. Cells primed to assemble alpha4-alpha4 proteasomes exhibit enhanced resistance to toxic metal ions. Taken together, our results establish the existence of an alternative mammalian proteasome isoform and suggest a potential role in enabling cells to adapt to environmental stresses. PMID- 26997269 TI - Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET. AB - Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs). Forster resonance energy transfer (FRET)-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC), and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R) on PKA's catalytic subunit. We discover that this mutation not only differentially affects PKAcat's binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET. PMID- 26997270 TI - Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus. AB - Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam(+)UEA1(-)Ly 51(+)PLET1(+)MHC class II(hi), which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c) TECs and medullary (m) TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1(+)Ly-51(+) TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients. PMID- 26997271 TI - Phosphorylation of CPAP by Aurora-A Maintains Spindle Pole Integrity during Mitosis. AB - CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM) dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. Interestingly, the dispersal of the PCM was effectively rescued by ectopic expression of wild-type CPAP or a phospho-mimic CPAP-S467D mutant, but not a non-phosphorylated CPAP-S467A mutant. Finally, we found that CPAP-S467D has a low affinity for microtubule binding but a high affinity for PCM proteins. Together, our results support a model wherein CPAP is required for proper mitotic progression, and phosphorylation of CPAP by Aurora-A is essential for maintaining spindle pole integrity. PMID- 26997272 TI - Mitotic History Reveals Distinct Stem Cell Populations and Their Contributions to Hematopoiesis. AB - Homeostasis of short-lived blood cells is dependent on rapid proliferation of immature precursors. Using a conditional histone 2B-mCherry-labeling mouse model, we characterize hematopoietic stem cell (HSC) and progenitor proliferation dynamics in steady state and following several types of induced stress. HSC proliferation following HSC transplantation into lethally irradiated mice is fundamentally different not only from native hematopoiesis but also from other stress contexts. Whereas transplantation promoted sustained, long-term proliferation of HSCs, both cytokine-induced mobilization and acute depletion of selected blood cell lineages elicited very limited recruitment of HSCs to the proliferative pool. By coupling mCherry-based analysis of proliferation history with multiplex gene expression analyses on single cells, we have found that HSCs can be stratified into four distinct subtypes. These subtypes have distinct molecular signatures and differ significantly in their reconstitution potentials, showcasing the power of tracking proliferation history when resolving functional heterogeneity of HSCs. PMID- 26997273 TI - Merlin/NF2-Lin28B-let-7 Is a Tumor-Suppressive Pathway that Is Cell-Density Dependent and Hippo Independent. AB - Contact inhibition of proliferation is critical for tissue organization, and its dysregulation contributes to tumorigenesis. Merlin/NF2 is a tumor suppressor that governs contact inhibition. Although Merlin/NF2 inhibits YAP1 and TAZ, which are paralogous Hippo pathway transcriptional co-activators and oncoproteins, it is not fully understood how Merlin/NF2-mediated signal transduction triggered by cell-cell contact exerts tumor suppression. Here, we identify Lin28B, an inhibitor of let-7 microRNAs (miRNAs), as an important downstream target of Merlin/NF2. Functional studies revealed that, at low cell density, Merlin/NF2 is phosphorylated and does not bind to Lin28B, allowing Lin28B to enter the nucleus, bind to pri-let-7 miRNAs, and inhibit their maturation in a YAP1/TAZ-independent manner. This inhibition of pri-let-7 maturation then promotes cell growth. However, cell-cell contact triggers Merlin/NF2 dephosphorylation, which sequesters Lin28B in the cytoplasm and permits pri-let-7 maturation. Our results reveal that Merlin/NF2-mediated signaling drives a tumor-suppressive pathway that is cell-density dependent and Hippo independent. PMID- 26997274 TI - NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia. AB - Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Surprisingly, RA stimulation in these cells results in enhanced chromatin association of the nucleosome remodeler BRG1. Inhibition of NPM or TOP2B abrogated BRG1 recruitment. Furthermore, NPM inhibition and targeting BRG1 restored differentiation when combined with RA. Here, we demonstrate a role for NPM and BRG1 in obstructing RA differentiation and implicate chromatin remodeling in mediating therapeutic resistance in malignancies. NPM mutations are the most common genetic change in patients with acute leukemia (AML); therefore, our model may be applicable to other more common leukemias driven by NPM. PMID- 26997275 TI - Antioxidant Defense by Thioredoxin Can Occur Independently of Canonical Thiol Disulfide Oxidoreductase Enzymatic Activity. AB - The thiol-disulfide oxidoreductase CXXC catalytic domain of thioredoxin contributes to antioxidant defense in phylogenetically diverse organisms. We find that although the oxidoreductase activity of thioredoxin-1 protects Salmonella enterica serovar Typhimurium from hydrogen peroxide in vitro, it does not appear to contribute to Salmonella's antioxidant defenses in vivo. Nonetheless, thioredoxin-1 defends Salmonella from oxidative stress resulting from NADPH phagocyte oxidase macrophage expression during the innate immune response in mice. Thioredoxin-1 binds to the flexible linker, which connects the receiver and effector domains of SsrB, thereby keeping this response regulator in the soluble fraction. Thioredoxin-1, independently of thiol-disulfide exchange, activates intracellular SPI2 gene transcription required for Salmonella resistance to both reactive species generated by NADPH phagocyte oxidase and oxygen-independent lysosomal host defenses. These findings suggest that the horizontally acquired virulence determinant SsrB is regulated post-translationally by ancestrally present thioredoxin. PMID- 26997276 TI - Evasion of Cell Senescence Leads to Medulloblastoma Progression. AB - How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1(+/-) mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH) is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutations are always subsequent to Ptch1 LOH. Introduction of a p53 mutation prevents senescence, accelerates tumor formation, and increases medulloblastoma incidence. Altogether, our results show that evasion of senescence associated with Ptch1 LOH allows progression to advanced tumors. PMID- 26997277 TI - alpha/beta-Hydrolase Domain 6 Deletion Induces Adipose Browning and Prevents Obesity and Type 2 Diabetes. AB - Suppression of alpha/beta-domain hydrolase-6 (ABHD6), a monoacylglycerol (MAG) hydrolase, promotes glucose-stimulated insulin secretion by pancreatic beta cells. We report here that high-fat-diet-fed ABHD6-KO mice show modestly reduced food intake, decreased body weight gain and glycemia, improved glucose tolerance and insulin sensitivity, and enhanced locomotor activity. ABHD6-KO mice also show increased energy expenditure, cold-induced thermogenesis, brown adipose UCP1 expression, fatty acid oxidation, and white adipose browning. Adipose browning and cold-induced thermogenesis are replicated by the ABHD6 inhibitor WWL70 and by antisense oligonucleotides targeting ABHD6. Our evidence suggests that one mechanism by which the lipolysis derived 1-MAG signals intrinsic and cell autonomous adipose browning is via PPARalpha and PPARgamma activation, and that ABHD6 regulates adipose browning by controlling signal competent 1-MAG levels. Thus, ABHD6 regulates energy homeostasis, brown adipose function, and white adipose browning and is a potential therapeutic target for obesity and type 2 diabetes. PMID- 26997278 TI - Alternative Splicing of G9a Regulates Neuronal Differentiation. AB - Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10) through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10(+) isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation. PMID- 26997279 TI - Metagenomic Sequencing with Strain-Level Resolution Implicates Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Preterm Infants. AB - Necrotizing enterocolitis (NEC) afflicts approximately 10% of extremely preterm infants with high fatality. Inappropriate bacterial colonization with Enterobacteriaceae is implicated, but no specific pathogen has been identified. We identify uropathogenic E. coli (UPEC) colonization as a significant risk factor for the development of NEC and subsequent mortality. We describe a large scale deep shotgun metagenomic sequence analysis of the early intestinal microbiome of 144 preterm and 22 term infants. Using a pan-genomic approach to functionally subtype the E. coli, we identify genes associated with NEC and mortality that indicate colonization by UPEC. Metagenomic multilocus sequence typing analysis further defined NEC-associated strains as sequence types often associated with urinary tract infections, including ST69, ST73, ST95, ST127, ST131, and ST144. Although other factors associated with prematurity may also contribute, this report suggests a link between UPEC and NEC and indicates that further attention to these sequence types as potential causal agents is needed. PMID- 26997281 TI - Rapid Elevation in CMPF May Act As a Tipping Point in Diabetes Development. AB - Prediabetes, a state of mild glucose intolerance, can persist for years before a sudden decline in beta cell function and rapid deterioration to overt diabetes. The mechanism underlying this tipping point of beta cell dysfunction remains unknown. Here, the furan fatty acid metabolite CMPF was evaluated in a prospective cohort. Those who developed overt diabetes had a significant increase in CMPF over time, whereas prediabetics maintained chronically elevated levels, even up to 5 years before diagnosis. To evaluate the effect of increasing CMPF on diabetes progression, we used obese, insulin-resistant models of prediabetes. CMPF accelerated diabetes development by inducing metabolic remodeling, resulting in preferential utilization of fatty acids over glucose. This was associated with diminished glucose-stimulated insulin secretion, increased ROS formation, and accumulation of proinsulin, all characteristics of human diabetes. Thus, an increase in CMPF may represent the tipping point in diabetes development by accelerating beta cell dysfunction. PMID- 26997282 TI - Genome-wide RNAi Screen Identifies Cohesin Genes as Modifiers of Renewal and Differentiation in Human HSCs. AB - To gain insights into the regulatory mechanisms of hematopoietic stem cells (HSCs), we employed a genome-wide RNAi screen in human cord-blood derived cells and identified candidate genes whose knockdown maintained the HSC phenotype during culture. A striking finding was the identification of members of the cohesin complex (STAG2, RAD21, STAG1, and SMC3) among the top 20 genes from the screen. Upon individual validation of these cohesin genes, we found that their knockdown led to an immediate expansion of cells with an HSC phenotype in vitro. A similar expansion was observed in vivo following transplantation to immunodeficient mice. Transcriptome analysis of cohesin-deficient CD34(+) cells showed an upregulation of HSC-specific genes, demonstrating an immediate shift toward a more stem-cell-like gene expression signature upon cohesin deficiency. Our findings implicate cohesin as a major regulator of HSCs and illustrate the power of global RNAi screens to identify modifiers of cell fate. PMID- 26997280 TI - Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit. AB - Kappa opioid receptors (KORs) are involved in a variety of aversive behavioral states, including anxiety. To date, a circuit-based mechanism for KOR-driven anxiety has not been described. Here, we show that activation of KORs inhibits glutamate release from basolateral amygdala (BLA) inputs to the bed nucleus of the stria terminalis (BNST) and occludes the anxiolytic phenotype seen with optogenetic activation of BLA-BNST projections. In addition, deletion of KORs from amygdala neurons results in an anxiolytic phenotype. Furthermore, we identify a frequency-dependent, optically evoked local dynorphin-induced heterosynaptic plasticity of glutamate inputs in the BNST. We also find that there is cell type specificity to the KOR modulation of the BLA-BNST input with greater KOR-mediated inhibition of BLA dynorphin-expressing neurons. Collectively, these results provide support for a model in which local dynorphin release can inhibit an anxiolytic pathway, providing a discrete therapeutic target for the treatment of anxiety disorders. PMID- 26997285 TI - Host-Guest Inclusion Complexation of alpha-Cyclodextrin and Triiodide Examined Using UV-Vis Spectrophotometry. AB - The historically relevant host-guest complexation of alpha-cyclodextrin (alpha CD) and triiodide (I3(-)) in aqueous solution was examined using a systematic UV vis spectrophotometric approach. This particular system is experimentally challenging because of the coupled equilibria, namely, I2 + I(-) ? I3(-) and alpha-CD + I3(-) ? alpha-CD.I3(-). We therefore developed a unique experimental approach that allowed us to determine the concentration of all iodine species. This enabled us to unequivocally demonstrate that the large increase in the UV absorbance with added alpha-cyclodextrin is due to an increase in the overall triiodide concentration as alpha-CD essentially converts iodine to triiodide according to the coupled equilibria. Herein we report (a) the complexation stoichiometry is 1:1 (i.e., the host-guest complex is alpha-CD.I3(-)), (b) the binding constant is KH-G = (1.35 +/- 0.05) * 10(5) M(-1) at room temperature, and PMID- 26997283 TI - Distinct Roles of the Prefrontal and Posterior Parietal Cortices in Response Inhibition. AB - The dorsolateral prefrontal cortex and posterior parietal cortex have been implicated in the planning of movements and inhibition of inappropriate responses, though their precise roles in these functions are not known. To address this question, we trained monkeys to perform memory-guided saccade and anti-saccade tasks and compared neural responses in the same animals. A population of neurons with no motor responses was also activated by a stimulus appearing out of the receptive field and could therefore mediate vector inversion. These neurons were found almost exclusively in the prefrontal cortex. Prefrontal cortical activity better predicted the level of performance in the task. Representation of the saccade goal also peaked in the prefrontal cortex at a time that was predictive of reaction time. These results suggest that the prefrontal cortex is the primary site of vector inversion in the cerebral cortex and explain the importance of this area in response inhibition. PMID- 26997284 TI - Associations between nitric oxide synthase 3 gene polymorphisms and preeclampsia risk: a meta-analysis. AB - Previous studies have examined the role of three NOS3 gene polymorphisms [G894T, T-786C, and the variable number of tandem repeats 4b/a (VNTR 4b/a)] in the susceptibility to preeclampsia with inconclusive findings. We therefore conducted an updated meta-analysis by including more studies. The most appropriate genetic model was chosen for each polymorphism by using a well-established method. Pooled results indicated that, compared with the GT+GG genotype, the TT genotype of G894T was associated with an increased risk of preeclampsia (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.21-1.77, P < 0.001; I(2) = 40.2%). The CC genotype of T-786C was also associated with a higher risk of preeclampsia (OR = 1.30; 95% CI = 1.07-1.58, P = 0.034; I(2) = 46.9%) than the CT + TT genotype. No association was found for VNTR 4b/a. Stratified analysis indicated that the increased risk was evident for high-quality studies both for G894T and T-786C, and for studies conducted among Caucasians and Africans for T-786C. However, the increased risk for T-786C among Africans needs further confirmation due to the high probability of false-positive reports. Our results suggested that G894T and T-786C polymorphisms, but not VNTR 4b/a, were associated with an increased risk of preeclampsia. PMID- 26997286 TI - Opportunities for the practice of health promotion: the assets model and NICE guidelines. PMID- 26997287 TI - Cardiovascular health education intervention in the Prison of Soria. AB - OBJECTIVE: To promote awareness of healthy lifestyles, to help decrease the risk factors that cause cardiovascular disease, obesity, diabetes, hypertension and hyperlipidemia, through Health Education (HE). MATERIAL AND METHODS: Between November and December 2014 in the prison of Soria, HE intervention in cardiovascular diseases was performed. Participation was offered to 160 inmates at the Prison. The intervention consisted of individual interviews with anthropometric assessment and review of medical records and three group sessions with theoretical and practical content of these diseases, as well as dietary recommendations, Mediterranean diet and exercise. Knowledge gained from surveys conducted for that purpose was evaluated. RESULTS: A total of 33 (21%) of 160. Average age 38.2 (35.2 to 41.3). PREVALENCE: Normal weight (BMI 18 to 24.9) 18 (54.5%), overweight BMI (25.0 to 29.9) 11 (33.3%), obesity (IBMI from 30) 4 (12. 1%). Cardiovascular risk (CVR) as ICC (waist hip ratio) 10 (30%) high risk, REGICOR 4 (12.1%) moderate risk. Relative risk of comorbidity in 2 (6.0%) had a slightly increased risk, 4 (12.1%) had increased risk. CONCLUSIONS: HE interventions are necessary and effective in modifying lifestyles. The calculation of CVT should serve to implement preventive measures to reduce the factors of cardiovascular risk. PMID- 26997288 TI - Mental disorder prevalence and associated risk factors in three prisons of Spain. AB - AIMS: To determine the lifetime and monthly prevalence of people with mental disorders and its association with sociodemographic factors and criminal risk in three Spanish prisons (Ocana, Madrid I, II and VI). METHOD: Cross-sectional epidemiological study of a sample of 184 inmates. Socio-demographic and criminal data were collected by an ad hoc interview. Mental disorders were assessed with the clinical version of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders Axis I Disorders (SCID-I). RESULTS: Life prevalence of mental disorders was 90.2%. The most common mental disorders and substance abuse or dependence was 72.3%, followed by mood disorder (38.5%) and psychotic disorders (34.2%). Moreover, the prevalence of any mental disorder in the last month was 52.2%. The main psychotic disorder (20.7%) was followed by substance abuse or dependence (18.5%), and mood disorder state (13%). A socio demographic profile as a risk for each disorder was found. DISCUSSION: The prevalence of people with mental disorders is very high in Spanish prisons, and is associated with a distinct demographic profile. It is essential to continue researching this reality, translating the results into therapeutic and preventive action adapted to the status of inmates to reduce social inequalities in this high priority public health situation. PMID- 26997289 TI - Intellectual disability and the prison setting. AB - INTRODUCTION: The prevalence of intellectual disability (ID) in the prison setting has scarcely been studied. Although some approximations or estimates regarding people with intellectual disabilities have been performed in Spain, there is little in the way of reliable data. OBJECTIVES: 1) To determine the prevalence of ID in a sample population in the residential modules of a Spanish prison, 2) Obtain data on the prevalence of ID in prison psychiatric units and hospitals. METHODS: 1) A TONI II test was performed on a sub-sample (n = 398) of a prevalence study in Spanish prisons to identify inmates with intellectual disabilities. 2) We reviewed the reports of the psychiatric department of Parc Sanitari Sant Joan de Deu to establish the diagnosis at discharge of patients with a primary diagnosis of intellectual disability 3) Data from the Directorate General of Prisons on the prevalence of ID in Prison Psychiatric Hospitals was reviewed. RESULTS: The data obtained from the TONI II test found 3.77% of the study population has an IQ below 70, and 7.54 % has a borderline IQ rate. Assessment of penitentiary psychiatric hospitalization data showed these figures to be higher. CONCLUSIONS: The data from a Spanish prison population showed that ID levels were higher than those in the community, especially amongst prisoners requiring specialized psychiatric care. What is also evident is that adequate resources are required in prisons and in the community to provide better care for people with intellectual disabilities who are in the pathway of the criminal justice system. PMID- 26997290 TI - Residency training in Fontcalent Prison Psychiatric Hospital. PMID- 26997292 TI - Reply. Residency training in Fontcalent Prison Psychiatric Hospital. PMID- 26997291 TI - Reply. Residency training in Fontcalent Prison Psychiatric Hospital. PMID- 26997293 TI - Borderline personality disorder and foreign body ingestion. PMID- 26997294 TI - [A woman with a pure seminoma and a contralateral intratubular germinal neoplasm. A case report]. AB - BACKGROUND: Androgen insensitivity syndrome is an X-linked disorder, and is characterised by a female phenotype in a chromosomally male individual. It usually occurs in puberty with primary amenorrhoea or as an inguinal tumour in a female infant. In recent years, it is often also diagnosed in fertility clinics in adulthood. OBJECTIVE: The case is presented of a pure seminoma in a woman with the reference diagnosis of inguinal hernia. CLINICAL CASE: A 53 year old woman, who was operated on in 2014 due to a nodule in left groin. Androgen insensitivity syndrome was corroborated, and histopathology reported it as a right testicular seminoma. DISCUSSION: The importance of early diagnosis is discussed, highlighting the consequences of misdiagnosis, and question whether these patients have been adequately treated in the past. The risk of malignant transformation of an undescended testicle increases with age, thus gonadectomy should be performed after puberty, and in some cases hormone replacement therapy. PMID- 26997295 TI - The burden of illness in patients with hyponatraemia in Sweden: a population based registry study. AB - BACKGROUND: Hyponatraemia (HN; serum sodium level < 135 mmol/l) is the most common electrolyte disturbance seen in clinical practice, and is associated with varying spectrum of symptoms. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common aetiology in hospitalised patients, and can be caused by several different underlying conditions. AIMS: The objectives of this study were to retrospectively examine the baseline characteristics, clinical outcomes and hospital resource utilisation of patients with HN and/or SIADH in Sweden over a 10-year period from 2001 to 2011. Additional analysis was performed on subpopulations of patients with hip fracture, pneumonia and small cell lung cancer (SCLC) to see if trends in outcomes were consistent across a broad range of aetiologies commonly associated with the condition. METHODS: Patient information was taken from the Swedish National Patient Registry, the Swedish Cancer Registry, the Swedish Cause of Death Register and the Swedish Prescribed Drug Register. A total of 34,537 patients (4.38%) were identified with HN and/or SIADH, with the incidence and prevalence rising over the 10-year study period. RESULTS: Of the 34,537 patients identified, 841 had hip fracture, 2635 had pneumonia and 106 had SCLC. Compared with matched control patients, those with HN and/or SIADH had a longer length of hospital stay, a higher re-admission rate and a shorter time to re-admission. CONCLUSIONS: This study showed that HN and/or SIADH negatively impact patient outcomes and healthcare resources related to hospital stay irrespective of the underlying cause. The impact of HN is not confined to the initial hospitalisation, as re-admission rates are also affected. PMID- 26997296 TI - 3D-Encapsulated iridium-complexed nanophosphors for highly efficient host-free organic light-emitting diodes. AB - Iridium-complexed nanosize phosphors 3D-encapsulated with nine 3,6-di-tert-butyl N-propyl-carbazole groups were constructed as host-dopant integrated systems, which achieved a high photoluminescence quantum yield beyond 70% from neat evaporated films, and an electroluminescence external quantum efficiency up to ~8.5% and near-zero roll-offs at 1000 cd m(-2) from its dual-layer host-free light-emitting diodes. PMID- 26997297 TI - Detection of intra-brain cytoplasmic 1 (BC1) long noncoding RNA using graphene oxide-fluorescence beacon detector. AB - Detection of cellular expression of long noncoding RNAs (lncRNAs) was elusive due to the ambiguity of exposure of their reactive sequences associated with their secondary/tertiary structures and dynamic binding of proteins around lncRNAs. Herein, we developed graphene-based detection techniques exploiting the quenching capability of graphene oxide (GO) flakes for fluorescent dye (FAM)-labeled single stranded siRNAs and consequent un-quenching by their detachment from GO by matching lncRNAs. A brain cytoplasmic 1 (BC1) lncRNA expression was significantly decreased by a siRNA, siBC1-1. GO quenched the FAM-labeled siBC1-1 peptide nucleic acid (PNA) probe, and this quenching was recovered by BC1. While FAM siBC1-1-PNA-GO complex transfected spontaneously mouse or human neural stem cells, fluorescence was recovered only in mouse cells having high BC1 expression. Fluorescent dye-labeled single-stranded RNA-GO probe could detect the reactive exposed nucleic acid sequence of a cytoplasmic lncRNA expressing in the cytoplasm, which strategy can be used as a detection method of lncRNA expression. PMID- 26997300 TI - Tabetic arthropathy of the knee: MRI aspects. PMID- 26997298 TI - The Psychoactive Designer Drug and Bath Salt Constituent MDPV Causes Widespread Disruption of Brain Functional Connectivity. AB - The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex. Male rats were imaged following administration of a single dose of MDPV (0.3, 1.0, or 3.0 mg/kg) or saline. Resting state brain blood oxygenation level-dependent (BOLD) images were acquired at 4.7 T. To determine the role of dopamine transmission in MDPV-induced changes in functional connectivity, a group of rats received the dopamine D1/D2 receptor antagonist cis flupenthixol (0.5 mg/kg) 30 min before MDPV. MDPV dose-dependently reduced functional connectivity. Detailed analysis of its effects revealed that connectivity between frontal cortical and striatal areas was reduced. This included connectivity between the prelimbic prefrontal cortex and other areas of the frontal cortex and the insular cortex with hypothalamic, ventral, and dorsal striatal areas. Although the reduced connectivity appeared widespread, connectivity between these regions and somatosensory cortex was not as severely affected. Dopamine receptor blockade did not prevent the MDPV-induced decrease in functional connectivity. The results provide a novel signature of MDPV's in vivo mechanism of action. Reduced brain functional connectivity has been reported in patients suffering from psychosis and has been linked to cognitive dysfunction, audiovisual hallucinations, and negative affective states akin to those reported for MDPV-induced intoxication. The present results suggest that disruption of functional connectivity networks involving frontal cortical and striatal regions could contribute to the adverse effects of MDPV. PMID- 26997299 TI - Novel Primate Model of Serotonin Transporter Genetic Polymorphisms Associated with Gene Expression, Anxiety and Sensitivity to Antidepressants. AB - Genetic polymorphisms in the repeat upstream region of the serotonin transporter gene (SLC6A4) are associated with individual differences in stress reactivity, vulnerability to affective disorders, and response to pharmacotherapy. However, the molecular, neurodevelopmental and psychopharmacological mechanisms underlying the link between SLC6A4 polymorphisms and the emotionally vulnerable phenotype are not fully understood. Thus, using the marmoset monkey Callithrix jacchus we characterize here a new neurobiological model to help to address these questions. We first sequenced the marmoset SLC6A4 promoter and identified a double nucleotide polymorphism (-2053AC/CT) and two single-nucleotide polymorphisms ( 2022C/T and -1592G/C) within the repeat upstream region. We showed their association with gene expression using in vivo quantitative PCR and with affective behavior using a primate test of anxiety (human intruder test). The low expressing haplotype (AC/C/G) was linked with high anxiety while the high expressing one (CT/T/C) was associated with an active coping strategy in response to threat. Pharmacological challenge with an acute dose of the selective serotonin reuptake inhibitor, citalopram, revealed a genotype-dependent behavioral response. While individuals homozygous for the high anxiety-related haplotype AC/C/G exhibited a dose-dependent, anxiogenic response, individuals homozygous for the low anxiety-related haplotype CT/T/C showed an opposing, dose dependent anxiolytic effect. These findings provide a novel genetic and behavioral primate model to study the molecular, neurodevelopmental, and psychopharmacological mechanisms that underlie genetic variation-associated complex behaviors, with specific implications for the understanding of normal and abnormal serotonin actions and the development of personalized pharmacological treatments for psychiatric disorders. PMID- 26997301 TI - Periodontal disease in patients with rheumatoid arthritis in Sub-Saharan Africa: A case-control study. PMID- 26997302 TI - Myeloma bone and extra-medullary disease: Role of PET/CT and other whole-body imaging techniques. AB - Multiple myeloma (MM) is the second most common hematological malignancy. Although it can affect different organs, the bone compartment stands out both in terms of prevalence and clinical impact. Despite the striking advances in MM therapy, bone disease can remarkably affect the patient's quality of life. The occurrence and extension of bone marrow and extra-medullary involvement should be carefully assessed to confirm the diagnosis, to locate and whenever possible prevent dreadful complications such as pathological fractures and spinal cord compression, and to establish suitable therapeutic measures. Many imaging techniques have been proposed for the detection of MM skeletal involvement. With the development of more sophisticated imaging tools, it is time to use the right technique at the right time. Based on the review of the literature and our own experience, this article discusses advantages and disadvantages of the different imaging methods in the work-up of MM patients, with particular emphasis on the role that PET/CT can play. It is emphasized that whole body low-dose computed tomography should be the preferred imaging technique at baseline. However, bone marrow infiltration and extra-medullary manifestations are better detected by whole body magnetic resonance imaging. Positron emission tomography/computed tomography, on the other hand, combines the benefits of the two mentioned imaging procedures and is particularly useful not only for the detection of osteolytic lesions unrevealed by conventional X-ray, but also in the assessment of prognosis and therapeutic response. PMID- 26997303 TI - The impact of preoperative corticosteroids on the systemic inflammatory response and postoperative complications following surgery for gastrointestinal cancer: A systematic review and meta-analysis. AB - BACKGROUND: This meta-analysis examined the impact of preoperative corticosteroids on interleukin 6 (IL-6), C-reactive protein (CRP), and complications following surgery for gastrointestinal cancer. METHODS: A systematic review was performed using appropriate keywords. Random-effects meta analysis was performed. RESULTS: 11 RCTs with 474 patients, were included. Corticosteroids were significantly associated with lower IL-6 on postoperative day 1 (mean difference -148pg/mL, 95% CI -205 to -92, p<0.001), 2 (-33pg/mL, 95% CI -58 to -8, p=0.01), and 3 (-31pg/mL, 95% CI -52 to -11, p=0.002), lower CRP on day 3 (-45mg/L, 95% CI -68 to -21, p<0.001), and 7 (-14mg/L, 95% CI -27 to -1, p=0.04), and fewer postoperative infective complications (OR 0.47, 95% CI 0.26 0.83, p=0.01). CONCLUSION: Corticosteroids were associated with reduction in the postoperative systemic inflammatory response and complications following surgery for gastrointestinal cancer. PMID- 26997304 TI - Dual-energy computed tomography: a promising novel preoperative localization study for treatment of primary hyperparathyroidism. AB - BACKGROUND: The objective of this study was to evaluate dual-energy computed tomography (DE-CT) for preoperative parathyroid tumor (PT) localization in individuals undergoing parathyroidectomy for treatment of primary hyperparathyroidism (PHP). METHODS: DE-CT was evaluated by retrospective review of the clinical and biochemical characteristics, imaging, operative findings, and outcomes for PHP cases undergoing an initial operation at a single center. RESULTS: The accuracy of each preoperative imaging test, based on operative findings and pathological confirmation of removal of a PT from the localized site was: 58% for ultrasound, 75% Tc-99m sestamibi noncontrast single photon emission noncontrast CT, and 75% for DE-CT. DE-CT was able to correctly localize a PT in a 3rd of cases that were nonlocalized. All study patients had normalization of serum calcium and parathyroid hormone levels postoperatively. CONCLUSIONS: DE-CT shows promise for the preoperative PT localization, especially in nonlocalized PHP cases, and warrants further investigation. PMID- 26997305 TI - Call to care: the impact of 24-hour postdischarge telephone follow-up in the treatment of surgical day care patients. AB - BACKGROUND: Patient satisfaction and effective management of postoperative complaints are important factors in determining the success of outpatient surgery programs. METHODS: In September 2013, a 24-hour postdischarge telephone follow-up (TFU) call was initiated by surgical day care nurses at the Royal Jubilee Hospital in Victoria, BC. The study group was contacted to evaluate the effectiveness of the TFU in identifying and addressing postoperative complaints and determining the level of satisfaction with discharge instructions and care. RESULTS: A total of 854 patients were contacted. Overall, 313 (36.7%) received TFU and 541 (63.3%) did not; these served as our control group. Independent sample t-tests revealed that patients who received TFU had significantly fewer postoperative complaints compared with the controls (.19 vs .28, respectively). CONCLUSIONS: Day surgery patients receiving TFU reported fewer postoperative concerns. Results of this study suggest that a TFU call results in increased patient satisfaction with discharge care and is an appropriate tool to address patients' postoperative complaints and improve patient-reported outcomes. PMID- 26997306 TI - Chiral Phosphoric Acid Catalyzed Asymmetric Ugi Reaction by Dynamic Kinetic Resolution of the Primary Multicomponent Adduct. AB - Reaction of isonitriles with 3-(arylamino)isobenzofuran-1(3H)-ones in the presence of a catalytic amount of an octahydro (R)-binol-derived chiral phosphoric acid afforded 3-oxo-2-arylisoindoline-1-carboxamides in high yields with good to high enantioselectivities. An enantioselective Ugi four-center three component reaction of 2-formylbenzoic acids, anilines, and isonitriles was subsequently developed for the synthesis of the same heterocycle. Mechanistic studies indicate that the enantioselectivity results from the dynamic kinetic resolution of the primary Ugi adduct, rather than from the C-C bond-forming process. The resulting heterocycle products are of significant medicinal importance. PMID- 26997307 TI - Personalized medicine in neuro-oncology. PMID- 26997308 TI - Comparison between the traditional non-guided and a novel ultrasound-guided technique for office fitting of intrauterine contraceptive devices. AB - OBJECTIVE: To investigate a novel method for in-office fitting of intrauterine contraceptive devices (IUCDs) by comparing it to the traditional non-guided technique. METHODS: A prospective cohort study comparing the application of intrauterine contraceptives was conducted between January 1, 2013 and January 31, 2015 at a university contraception clinic, in Alexandria, Egypt. Patients aged 20 45years who were parous, had previously undergone vaginal or abdominal deliveries, and were requesting device insertion were included. Patients were randomly assigned to have devices fitted using the non-guided approach, with vaginal ultrasonography to plan and confirm device placement, or by the abdominal ultrasonography-guided technique. The primary outcomes were successful IUCD insertion and ideal device position 1week after insertion. Participants, counselors, and data analysts were masked to treatment assignments. RESULTS: Analyses included 40 patients in each treatment arm. Successful fitting was achieved in 32 (80%) patients in the non-guided arm and 39 (98%) patients in the ultrasonography-guided arm (P=0.04). Ideal placement was achieved in 38 (95%) patients in the ultrasonography-guided arm compared with 27 (68%) patients in the non-guided arm (P=0.02). CONCLUSION: Ultrasonography-guided IUCD insertion demonstrated improved success and fitting accuracy in comparison with a traditional, non-guided approach. ANZCTR trial ID: ACTRN12615000526572. PMID- 26997309 TI - Systemic Nonurological Symptoms in Patients with Overactive Bladder. AB - PURPOSE: We compare the systemic (nonurological) symptoms between patients with overactive bladder and subjects without overactive bladder. We also compare the urinary symptoms, quality of life and psychosocial measures between the 2 subgroups of patients with overactive bladder with a high vs low systemic symptom burden. MATERIALS AND METHODS: Patients diagnosed with overactive bladder (51) and age matched individuals without overactive bladder (30) were administered the polysymptomatic, polysyndromic questionnaire to assess the numbers and distribution of systemic symptoms across multiple organ systems. Validated instruments were administered to evaluate urinary symptoms (ICIQ-UI, ICIQ-OAB, OAB-q, USS), quality of life (UDI-6, IIQ-7, OAB-q) and psychosocial difficulties (depression, anxiety, stress, sexual trauma, sleep, fatigue). Patients with overactive bladder were divided into 2 subgroups (with and without widespread systemic symptoms) and their responses were compared. RESULTS: Patients with overactive bladder reported significantly more systemic (nonurological) symptoms compared to controls (mean +/- SD 17.5 +/- 12.3 vs 6.4 +/- 7.9 symptoms, p <0.001). Differences were observed across multiple organ systems (neurologic, cardiopulmonary, gastrointestinal, sexual, musculoskeletal and gynecologic, p <0.05). About a third of patients with overactive bladder (31.4%) reported widespread systemic symptoms across multiple organ systems (mean 32.0 symptoms). The presence of widespread systemic symptoms among patients with overactive bladder was correlated with worse incontinence/overactive bladder symptoms (ICIQ UI, OAB-q), poorer quality of life (UDI-6, IIQ-7, OAB-q) and more psychosocial difficulties (depression, anxiety, fatigue and higher stress, p <0.05). CONCLUSIONS: The increased presence of nonurological symptoms in overactive bladder suggests an underlying systemic etiology and pathogenetic mechanisms that may contribute to overactive bladder. This study highlights the importance of understanding systemic factors in urological conditions otherwise thought to be organ specific. PMID- 26997310 TI - Long-Term Quality of Life and Functional Outcomes among Primary and Secondary Artificial Urinary Sphincter Implantations in Men with Stress Urinary Incontinence. AB - PURPOSE: There remains a paucity of data regarding subjective and functional outcomes after artificial urinary sphincter implantation. Therefore, we evaluated long-term differences in quality of life after primary and secondary artificial urinary sphincter surgery. MATERIALS AND METHODS: Men were invited to participate in a mail-in survey assessing artificial urinary sphincter status, patient satisfaction and urinary control. Patients with primary (467) and secondary (122) artificial urinary sphincter devices without an event were included in the study. Differences between the cohorts including quality of life (10-point scale, maximum 100) and functional outcomes were evaluated. RESULTS: Overall 229 (49%) patients with primary and 49 (40%) with secondary artificial urinary sphincters completed the survey at a median of 8.3 years. Patients with primary and secondary artificial urinary sphincter devices reported similar artificial urinary sphincter quality of life (score 74 vs 74). There were no significant differences in urinary continence outcomes including use of 1 pad or less daily (56% vs 55%), frequency of leakage 1 time or more per day (81% vs 71%) or degree of minimal leakage related bother (64% vs 55%). At less than 5 vs 10 or more years there was a significant reduction in artificial urinary sphincter quality of life (86 vs 73, p=0.007). Urinary continence also declined with time, including perceived urinary control (85% vs 53%, p=0.004), minimal leakage related bother (76% vs 59%, p=0.05) and use of 1 pad or less daily (67% vs 55%, p=0.07). On univariate analysis no clinical variables, including secondary revision, were associated with satisfaction or continence outcomes. CONCLUSIONS: We noted a high level of artificial urinary sphincter quality of life, acceptable urinary control and no difference in functional outcomes between men undergoing primary or secondary artificial urinary sphincter surgery. However, the time related decline in satisfaction and continence highlights the need for patient counseling regarding long-term artificial urinary sphincter functional outcomes. PMID- 26997311 TI - Characteristics of Anteriorly Located Prostate Cancer and the Usefulness of Multiparametric Magnetic Resonance Imaging for Diagnosis. AB - PURPOSE: We analyzed the pathological and oncologic characteristics of anteriorly located prostate cancer and assessed the usefulness of magnetic resonance imaging to detect anterior prostate cancer. MATERIALS AND METHODS: We analyzed the records of 728 consecutive patients treated with radical prostatectomy. Patients were categorized with anterior or prostate cancer or tumors involving the anterior and posterior prostate according to the dominant tumor location on whole mount section. RESULTS: The anterior and posterior prostate cancer groups and the group with cancer at both locations represented 31.0%, 46.7% and 22.3% of the total number of patients, respectively. Anterior prostate cancer was less commonly palpable (p <0.001) and needed more frequent repeat biopsy (p = 0.012) than posterior prostate cancer. Moreover, the anterior group had fewer positive cores than the posterior group (p <0.001) despite comparable tumor volumes. Gleason score upgrading was more frequently observed in anterior than in posterior prostate cancer (p = 0.003). However, final pathological features did not significantly differ. Only the seminal vesicle involvement rate was lower in anterior than in posterior prostate cancer (p <0.001). Estimated 5-year biochemical recurrence-free survival in patients with anterior prostate cancer was 87.5%, significantly higher than in patients with posterior prostate cancer (77.4%, p = 0.001) and patients with anterior plus posterior involvement (74.4%, p <0.001). Multivariate analysis revealed that anterior location was an independent prognostic factor for biochemical recurrence (HR 0.403) along with other well-known prognostic factors. To detect anterior prostate tumors the sensitivity and specificity of magnetic resonance imaging were 78.1% and 58.2%, respectively. CONCLUSIONS: Anterior prostate cancer had pathological features and favorable oncologic outcomes comparable to those of posterior prostate cancer but also more frequent Gleason score upgrading. Magnetic resonance imaging had moderate diagnostic performance for detecting lesions in the anterior prostate. PMID- 26997313 TI - Outcomes of Shock Wave Lithotripsy and Ureteroscopy for Treatment of Pediatric Urolithiasis. AB - PURPOSE: Shock wave lithotripsy has been commonly used to treat children with renal and ureteral calculi but recently ureteroscopy has been used more frequently. We examined postoperative outcomes from these 2 modalities in children. MATERIALS AND METHODS: We reviewed linked inpatient, ambulatory surgery and emergency department data from 2007 to 2010 for 5 states to identify pediatric admissions for renal/ureteral calculi treated with shock wave lithotripsy or ureteroscopy. Unplanned readmissions, additional procedures and emergency room visits were extracted. Multivariate logistic regression using generalized estimating equations to adjust for hospital level clustering was performed. RESULTS: We identified 2,281 admissions (1,087 for shock wave lithotripsy and 1,194 for ureteroscopy). Ages of patients undergoing ureteroscopy and those undergoing shock wave lithotripsy were similar (median 17.0 years for both cohorts, p = 0.001) but patients were more likely to be female (63.4% vs 54.7%, p <0.0001), to be privately insured (69.8% vs 62.2%, p <0.0005) and to have a ureteral stone (81.0% vs 34.8%, p <0.0001). Patients undergoing ureteroscopy demonstrated a lower rate of additional stone related procedures within 12 months (13.6% vs 18.8%, p <0.0007) but a higher rate of readmissions (10.8% vs 6.3%, p <0.0002) and emergency room visits (7.9% vs 4.9%, p <0.0036) within 30 days postoperatively. On multivariable analysis patients undergoing ureteroscopy were nearly twice as likely to visit an emergency room within 30 days of the procedure (OR 1.97, p <0.001) and to be readmitted to inpatient services (OR 1.71, p <0.01). CONCLUSIONS: Ureteroscopy is now used more commonly than shock wave lithotripsy for initial pediatric stone intervention. Although repeat treatment rates did not differ between procedures, ureteroscopy patients were more likely to be seen at an emergency room or hospitalized within 30 days of the initial procedure. PMID- 26997314 TI - Outcomes of Autologous Fascia Pubovaginal Sling for Patients with Transvaginal Mesh Related Complications Requiring Mesh Removal. AB - PURPOSE: We reviewed the outcomes of the autologous fascial pubovaginal sling as a salvage procedure for recurrent stress incontinence after intervention for polypropylene mesh erosion/exposure and/or bladder outlet obstruction in patients treated with prior transvaginal synthetic mesh for stress urinary incontinence. MATERIALS AND METHODS: In a review of surgical databases at 2 institutions between January 2007 and June 2013 we identified 46 patients who underwent autologous fascial pubovaginal sling following removal of transvaginal synthetic mesh in simultaneous or staged fashion. This cohort of patients was evaluated for outcomes, including subjective and objective success, change in quality of life and complications between those who underwent staged vs concomitant synthetic mesh removal with autologous fascial pubovaginal sling placement. RESULTS: All 46 patients had received at least 1 prior mesh sling for incontinence and 8 (17%) had received prior transvaginal polypropylene mesh for pelvic organ prolapse repair. A total of 30 patients underwent concomitant mesh incision with or without partial excision and autologous sling placement while 16 underwent staged autologous sling placement. Mean followup was 16 months. Of the patients 22% required a mean of 1.8 subsequent interventions an average of 6.5 months after autologous sling placement with no difference in median quality of life at final followup. At last followup 42 of 46 patients (91%) and 35 of 46 (76%) had achieved objective and subjective success, respectively. There was no difference in subjective success between patients treated with a staged vs a concomitant approach (69% vs 80%, p = 0.48). CONCLUSIONS: Autologous fascial pubovaginal sling placement after synthetic mesh removal can be performed successfully in patients with stress urinary incontinence as a single or staged procedure. PMID- 26997316 TI - A method for detailed analysis of the structure of mast cell secretory granules by negative contrast imaging. AB - Secretory granules (SGs) in mast cells contain various molecules that elicit allergy symptoms and are generally considered therapeutic targets. However, the biogenesis, maintenance, regulation, and recycling of these granules remain controversial, mainly due to the lack of suitable live-cell imaging methods. In this study, we applied negative contrast imaging with soluble green fluorescent protein (GFP) expressed in the cytoplasm as a method to validate structural information of mast cell SGs. We evaluated the accuracy of the method in detail, and we demonstrated that it can be used for quantitative analysis. Using this technique, secretory granules, the nucleus, mitochondria, and the cell body were visualized in individual RBL-2H3 mast cells without any influence. When combined with conventional multicolor fluorescence imaging, visualization of SG-associated proteins and SG-SG fusion was achieved. Moreover, 3D images were constructed based on this method, and detailed information on the number, size, and shape of individual SGs was obtained. We found that cell volume was correlated with SG number. In summary, the technique provides valuable and unique data, and will therefore advance SG research. PMID- 26997315 TI - Chronic Prostatitis Induces Bladder Hypersensitivity and Sensitizes Bladder Afferents in the Mouse. AB - PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome causes symptoms that include the frequent and urgent need to urinate, pain or burning during urination and pain radiating to the back, abdomen and/or colorectum. These bladder symptoms suggest that chronic prostatitis/chronic pelvic pain syndrome is associated with sensitization of adjacent organs, termed cross-organ sensitization. The objective of this study was to determine the extent of 1) changes in immunomodulatory mediators in the prostate and bladder after inflammation of the prostate and 2) bladder function and bladder afferent sensitization. MATERIALS AND METHODS: Prostate and bladder histology, immunohistochemistry and expression of immunomodulatory targets were examined weekly after zymosan or vehicle was injected in the dorsal lobe of the mouse prostate. Cystometry, bladder and bladder afferent sensitivity were also assessed weekly. RESULTS: Prostate inflammation induced significant up-regulation in proinflammatory and anti inflammatory cytokines TNF-alpha (tumor necrosis factor-alpha) and IL-10 (interleukin-10), growth factor NGF (nerve growth factor), and T-lymphocyte markers FoxP3, CD4 and CD8 in the prostate and the bladder. Notably, prostatitis significantly increased urinary voiding frequency, induced hypersensitivity to bladder distension and sensitized bladder afferents. We also examined sensory (afferent) co-innervation by injecting retrograde tracers DiI and Fast Blue in the bladder wall and the prostate, respectively. This showed that a significant proportion (approximately 17%) of dorsal root ganglion afferent somata contained tracers from the bladder and the prostate. CONCLUSIONS: These observations support an afferent contribution to chronic prostatitis/chronic pelvic pain syndrome and cross-organ sensitization from prostate to bladder. PMID- 26997317 TI - An evaluation of a body image intervention in adolescent girls delivered in single-sex versus co-educational classroom settings. AB - Body dissatisfaction is now recognized as having considerable negative impact on social, psychological, and physical health, particularly in adolescent girls. Consequently, we have developed a six-session co-educational body image intervention (Happy Being Me Co-educational) designed to reduce body dissatisfaction and its risk factors in Grade 7 girls. In addition to evaluating the program's efficacy, we aimed to identify whether girls would benefit equally when it was delivered as a universal intervention to a whole class including both boys and girls (co-educational delivery), or delivered as a selective intervention to girls only (single-sex delivery). Participants were 200 Grade 7 girls from five schools in Melbourne, Australia. Schools were randomly allocated to receive the intervention in single-sex classes (n=74), co-educational classes (n=73), or participate as a no-intervention control (n=53). Girls completed self report assessments of body dissatisfaction, psychological (internalization of the thin ideal, appearance comparison, and self-esteem) and peer environment (weight related teasing and appearance conversations) risk factors for body dissatisfaction, and dietary restraint, at baseline, post-intervention, and at 6 month follow-up. Significant improvements in body dissatisfaction and psychological risk factors were observed in the intervention group at post intervention and these were maintained at follow-up for psychological risk factors. Importantly, no significant differences between universal and selective delivery were observed, suggesting that the intervention is appropriate for dissemination in both modes. PMID- 26997318 TI - Optimization of Pyrogallol Autoxidation Conditions and Its Application in Evaluation of Superoxide Anion Radical Scavenging Capacity for Four Antioxidants. AB - In this study, some factors influencing pyrogallol autoxidation, including EDTA, temperature, and solvent, were systematically investigated to improve its feasibility in the evaluation of antioxidants for the first time. Subsequently, the improved pyrogallol autoxidation conditions were used to assess the superoxide anion scavenging activity (SASA) of four commonly used antioxidants, namely, ascorbic acid, rutin, catechin, and gallic acid, by both the reaction rate method and the terminated method. The results indicate that pyrogallol autoxidation could be successfully used to determine the antioxidant capacity of ascorbic acid and rutin, which correspondingly suggests the feasibility of its use to measure the superoxide anion radical scavenging activity of polysaccharides and flavonols, because these compounds have a similar basic structural unit as ascorbic acid and rutin, respectively. Unexpectedly, however, pyrogallol autoxidation cannot be used to evaluate the SASA of catechin and gallic acid, although their good antioxidant capacity was confirmed by the 1,1 diphenyl-2-picrylhydrazyl assay. Together, these results suggest the importance of noting the conditions used for pyrogallol autoxidation when assessing the SASA of targeted compounds. PMID- 26997319 TI - MAO and aggression. PMID- 26997320 TI - Rebuttal from Max C. Petersen and Michael J. Jurczak. PMID- 26997321 TI - Application of extensively targeted next-generation sequencing for the diagnosis of primary immunodeficiencies. PMID- 26997322 TI - Interpreting daily heart rate variability changes in collegiate female soccer players. AB - BACKGROUND: Heart rate variability (HRV) is an objective physiological marker that may be useful for monitoring training status in athletes. However, research aiming to interpret daily HRV changes in female athletes is limited. The objectives of this study were: 1) to assess daily HRV (i.e., log-transformed root mean square of successive R-R interval differences, lnRMSSD) trends both as a team and intra-individually in response to varying training load (TL); and 2) to determine relationships between lnRMSSD fluctuation (coefficient of variation, lnRMSSDcv) and psychometric and fitness parameters in collegiate female soccer players (N.=10). METHODS: Ultra-short, Smartphone-derived lnRMSSD and psychometrics were evaluated daily throughout 2 consecutive weeks of high and low TL. After the training period, fitness parameters were assessed. RESULTS: When compared to baseline, reductions in lnRMSSD ranged from unclear to very likely moderate during the high TL week (effect size +/-90% confidence limits [ES+/-90% CL] =-0.21+/-0.74 to -0.64+/-0.78, respectively) while lnRMSSD reductions were unclear during the low TL week (ES+/-90% CL=-0.03+/-0.73 to -0.35+/-0.75, respectively). A large difference in TL between weeks was observed (ES+/-90% CL=1.37+/-0.80). Higher lnRMSSDcv was associated with greater perceived fatigue and lower fitness (r [upper and lower 90% CL]=-0.55 [-0.84, -0.003] large, -0.65 [-0.89, -0.15] large). CONCLUSIONS: Athletes with lower fitness or higher perceived fatigue demonstrated greater reductions in lnRMSSD throughout training. This information can be useful when interpreting individual lnRMSSD responses throughout training for managing player fatigue. PMID- 26997323 TI - Is orienteering associated with allergic rhinitis in adolescents? AB - BACKGROUND: Allergic rhinitis (AR) is a disease that reduces athletic performance. Environmental allergen exposure is higher in outdoor sports (such as orienteering) than indoor sports. The main purpose of this study was to investigate the AR frequency in orienteers comparing with indoor athletes. METHODS: Sixty adolescent athletes (33 orienteers, 27 basketball players) enrolled this prospective study. AR diagnosis was made by both history (ISAAC questionnaire) and physical examination. Nasal endoscopy was performed to observe objective findings (concha hypertrophy, mucosal paleness, serosity, septum deviation, adenoid hypertrophy). Epidermal prick test, pulmonary function test, total IgE and serum eosinophil levels were also assessed. RESULTS: AR was diagnosed in 21 (35%) athletes. 14 (42.4%) were orienteers and 7 (25.9%) were basketball players (P=0.144). Endoscopic findings and skin test positivity were also seen at higher percentages in orienteers with no significance. Training age (sport duration), total IgE levels and skin test positivity were significantly higher in rhinitic orieenters than non-rhinitic orieenters (P=0.046, P=0.0001, and P=0.004, respectively). CONCLUSIONS: Although adolescent orieenters had some higher allergic parameters than indoor athletes, they were not found more susceptible to AR. It seems that the frequency of AR increases with longer training age in orieentering sport. This study is the first report about AR in adolescent orienteers. Future researchs should more focus on comparing allergic conditions between outdoor and indoor sports. PMID- 26997324 TI - Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response. AB - BACKGROUND: Cellular T-helper (Th)17 infiltrates dominate skin inflammation in filaggrin-deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss-of-function mutations in the filaggrin gene (FLG) for increased peripheral Th17 cells is unclear. OBJECTIVES: To study whether mutations in FLG influence the frequency of peripheral Th17 cells. METHODS: We studied blood samples from six adults with mutations in FLG and five controls without mutations for frequencies of cytokine-producing CD4(+) T cells. We evaluated ft/ft mice and wild-type (WT) control mice for interleukin (IL)-17-producing CD4(+) T cells in naive mice and following 2,4-dinitrofluorobenzene (DNFB) challenge. In addition, the T-cell receptor (TCR) Vbeta-chain repertoire was analysed by flow cytometry. RESULTS: Human studies showed increased frequency of peripheral Th17 cells in FLG mutation carriers when compared with WT individuals. Mouse studies showed increased frequency of peripheral Th17 cells in adult ft/ft mice but not in 2 week-old ft/ft mice. Moreover, altered TCR Vbeta-chain repertoire was found in ft/ft mice when compared with WT mice. An increased frequency of CD4(+) Vbeta10(+) T cells producing IL-17 was found in the spleen of adult ft/ft mice when compared with WT mice. Finally, DNFB challenge induced an increased number of Th17 cells in ft/ft mice compared with WT mice. CONCLUSIONS: Deficiency of filaggrin appeared to be a driver of increased peripheral levels of Th17 cells. This increase must be acquired as peripheral Th17 cells were found in adult ft/ft mice but not in 2-week-old ft/ft mice indicating involvement of exogenous factors. PMID- 26997325 TI - Anatomical study of the dorsal cutaneous branch of the ulnar nerve (DCBUN) and its clinical relevance in TFCC repair. AB - The aim of this study was to define a detailed description of the dorsal cutaneous branch of the ulnar nerve (DCBUN) in particular in relevance to triangular fibrocartilage complex (TFCC) repairs. In 20 formalin-embalmed arms, the DCBUN was dissected, and the course in each arm was mapped and categorized. Furthermore, the point of origin of the DCBUN, that is, from the ulnar nerve in association with the ulnar styloid process, was defined. Finally, the distance between the ulnar styloid process and the branching of the radial-ulnar communicating branch (RUCB) and the first branch of DCBUN was measured. The distance between the origin of the DCBUN in relation to the ulnar styloid process ranges from 55 to 111 mm (mean 87 mm; STD 14 mm). The distance between the ulnar styloid process and the RUCB ranges from 1 to 54 mm (mean 19 mm; STD 12 mm). Finally, the distance between the ulnar styloid process and the lateral distal branch shows a range of -6 to 28 mm (mean 10 mm; STD 9 mm). In general, three dorsal digital nerves (medial, intermediate, and lateral branch), run at the dorsal ulnar aspect of the hand. The RUCB is often less abundant and shows a large amount of variation. No complete safe zone could be identified; the course of the DCBUN suggests a longitudinal incision for the 6R portal. In fact, a more dorsal incision also prevents damage to the main branches of the DCBUN. PMID- 26997326 TI - Analysis of the microcirculation after soft tissue reconstruction of the outer ear with burns in patients with severe burn injuries. AB - Reconstruction of soft tissue defects of the ear with burns remains one of the most difficult tasks for the reconstructive surgeon. Although numerous reconstructive options are available, the results are often unpredictable and worse than expected. Besides full and split skin grafting, local random pattern flaps and pedicled flaps are frequently utilized to cover soft tissue defects of the outer auricle. Because of the difficulty and unpredictable nature of outer ear reconstruction after burn injury, a case-control study was conducted to determine the best reconstructive approach. The microcirculatory properties of different types of soft tissue reconstruction of the outer ear with burns in six severely burned Caucasian patients (three men and three women; mean age, 46 years (range, 22-70)) were compared to those in the healthy tissue of the outer ear using the O2C device (Oxygen to See; LEA Medizintechnik, Giebetaen, Germany). The results of this study revealed that the investigated microcirculation parameters such as the median values of blood flow (control group: 126 AU), relative amount of hemoglobin (control group: 59.5 AU), and tissue oxygen saturation (control group: 73%) are most similar to those of normal ear tissue when pedicled flaps based on the superficial temporal artery were used. These findings suggest that this type of reconstruction is superior for soft tissue reconstruction of the outer ear with burns in contrast to random pattern flaps and full skin grafts regarding the microcirculatory aspects. These findings may improve the knowledge on soft tissue viability and facilitate the exceptional and delicate process of planning the reconstruction of the auricle with burns. PMID- 26997327 TI - C.P.R. for the "Re:" Letter to the Editor? PMID- 26997328 TI - Inhibition of Glycogen Synthase Kinase-3beta (GSK-3beta) as potent therapeutic strategy to ameliorates L-dopa-induced dyskinesia in 6-OHDA parkinsonian rats. AB - Levodopa (L-dopa) is the dominating therapy drug for exogenous dopaminergic substitution and can alleviate most of the manifestations of Parkinson's disease (PD), but long-term therapy is associated with the emergence of L-dopa-induced dyskinesia (LID). Evidence points towards an involvement of Glycogen Synthase Kinase-3beta (GSK-3beta) in development of LID. In the present study, we found that animals rendered dyskinetic by L-dopa treatment, administration of TDZD8 (2mg/kg) obviously prevented the severity of AIM score, as well as improvement in motor function (P < 0.05). Moreover, the TDZD8-induced reduction in dyskinetic behavior correlated with a reduction in molecular correlates of LID. TDZD8 reduced the phosphorylation levels of tau, DARPP32, ERK and PKA protein, which represent molecular markers of LID, as well as reduced L-dopa-induced FosB mRNA and PPEB mRNA levels in the lesioned striatum. In addition, we found that TDZD8 antidyskinetic properties were overcome by D1 receptor, as pretreatment with SKF38393 (5 mg/kg, 10 mg/kg, respectively), a D1 receptor agonist, blocked TDZD8 antidyskinetic actions. This study supported the hypothesis that GSK-3beta played an important role in the development and expression of LID. Inhibition of GSK 3beta with TDZD8 reduced the development of ALO AIM score and associated molecular changes in 6-OHDA-lesioned rats. PMID- 26997329 TI - Tooth enamel properties and morphology after microabrasion: an in situ study. AB - AIM: This study evaluated the effect of saliva on enamel after microabrasion with different microabrasive compounds under in situ conditions. METHODS: Enamel/dentin blocks (16 mm2 ) from bovine incisors were divided into nine groups (n = 19): one control group (no treatment), four groups treated with microabrasion using 35% phosphoric acid (H3 PO4 ) + pumice, and the last four groups treated with microabrasion using 6.6% hydrochloric acid (HCl) + silica. The treated groups were subdivided according to the in situ regimen: without salivary exposure, 1 h, 24 h, or 7 days of saliva exposure. Surface microhardness (SMH) and cross-sectional microhardness (CSMH) were tested. Scanning electron microscopy (SEM) was used to evaluate enamel morphology. Microhardness data were tested by analysis of variance, and Tukey's and Dunnett's tests (alpha = 0.05). RESULTS: The SMH analysis revealed that all the microabrasion-treated groups presented significantly-reduced SMH values when compared to the control group (P < 0.05). Treatment with HCl + silica was more prone to the effect of saliva than H3 PO4 + pumice, even for CSMH analysis, once the superficial layers reached the same microhardness of that of the control group (P > 0.05). These results were confirmed by SEM, which demonstrated the mineral recovery effect over time. CONCLUSION: Saliva was effective in promoting the rehardening of enamel after microabrasion, mainly for the surfaces treated with HCl + silica. PMID- 26997330 TI - Direct and quasi-direct band gap silicon allotropes with remarkable stability. AB - In our present work, five previously proposed sp(3) carbon crystals were suggested as silicon allotropes and their stabilities, electronic and optical properties were investigated using the first-principles method. We find that these allotropes with direct or quasi-direct band gaps in a range of 1.2-1.6 eV are very suitable for applications in thin-film solar cells. They display strong adsorption coefficients in the visible range of sunlight in comparison with diamond silicon. These five silicon allotropes are confirmed to possess positive dynamical stability and remarkable themodynamical stability close to that of diamond silicon. In particular, the direct band gap M585-silicon possessing energy higher than diamond silicon only 25 meV per atom is expected to be experimentally produced for thin-film solar cells. PMID- 26997331 TI - Metabolic engineering of folate and its precursors in Mexican common bean (Phaseolus vulgaris L.). AB - Folate (vitamin B9) deficiency causes several health problems globally. However, folate biofortification of major staple crops is one alternative that can be used to improve vitamin intakes in populations at risk. We increased the folate levels in common bean by engineering the pteridine branch required for their biosynthesis. GTP cyclohydrolase I from Arabidopsis (AtGchI) was stably introduced into three common bean Pinto cultivars by particle bombardment. Seed specific overexpression of AtGCHI caused significant increases of up to 150-fold in biosynthetic pteridines in the transformed lines. The pteridine boost enhanced folate levels in raw desiccated seeds by up to threefold (325 MUg in a 100 g portion), which would represent 81% of the adult recommended daily allowance. Unexpectedly, the engineering also triggered a general increase in PABA levels, the other folate precursor. This was not observed in previous engineering studies and was probably caused by a feedforward mechanism that remains to be elucidated. Results from this work also show that common bean grains accumulate considerable amounts of oxidized pteridines that might represent products of folate degradation in desiccating seeds. Our study uncovers a probable different regulation of folate homoeostasis in these legume grains than that observed in other engineering works. Legumes are good sources of folates, and this work shows that they can be engineered to accumulate even greater amounts of folate that, when consumed, can improve folate status. Biofortification of common bean with folates and other micronutrients represents a promising strategy to improve the nutritional status of populations around the world. PMID- 26997332 TI - Distributing coil elements in three dimensions enhances parallel transmission multiband RF performance: A simulation study in the human brain at 7 Tesla. AB - PURPOSE: We explore the advantages of using a double-ring radiofrequency (RF) array and slice orientation to design parallel transmission (pTx) multiband (MB) pulses for simultaneous multislice (SMS) imaging with whole-brain coverage at 7 Tesla (T). METHODS: A double-ring head array with 16 elements split evenly in two rings stacked in the z-direction was modeled and compared with two single-ring arrays consisting of 8 or 16 elements. The array performance was evaluated by designing band-specific pTx MB pulses with local specific absorption rate (SAR) control. The impact of slice orientations was also investigated. RESULTS: The double-ring array consistently and significantly outperformed the other two single-ring arrays, with peak local SAR reduced by up to 40% at a fixed excitation error of 0.024. For all three arrays, exciting sagittal or coronal slices yielded better RF performance than exciting axial or oblique slices. CONCLUSIONS: A double-ring RF array can be used to drastically improve SAR versus excitation fidelity tradeoff for pTx MB pulse design for brain imaging at 7 T; therefore, it is preferable against single-ring RF array designs when pursuing various biomedical applications of pTx SMS imaging. In comparing the stripline arrays, coronal and sagittal slices are more advantageous than axial and oblique slices for pTx MB pulses. Magn Reson Med 75:2464-2472, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26997333 TI - Polycyclic aromatic hydrocarbons at fire stations: firefighters' exposure monitoring and biomonitoring, and assessment of the contribution to total internal dose. AB - This work characterizes levels of eighteen polycyclic aromatic hydrocarbons (PAHs) in the breathing air zone of firefighters during their regular work shift at eight Portuguese fire stations, and the firefighters' total internal dose by six urinary monohydroxyl metabolites (OH-PAHs). Total PAHs (SigmaPAHs) concentrations varied widely (46.4-428ng/m3), mainly due to site specificity (urban/rural) and characteristics (age and layout) of buildings. Airborne PAHs with 2-3 rings were the most abundant (63.9-95.7% SigmaPAHs). Similarly, urinary 1-hydroxynaphthalene and 1-hydroxyacenaphthene were the predominant metabolites (66-96% SigmaOH-PAHs). Naphthalene contributed the most to carcinogenic SigmaPAHs (39.4-78.1%) in majority of firehouses; benzo[a]pyrene, the marker of carcinogenic PAHs, accounted with 1.5-10%. Statistically positive significant correlations (r>=0.733, p<=0.025) were observed between SigmaPAHs and urinary SigmaOH-PAHs for firefighters of four fire stations suggesting that, at these sites, indoor air was their major exposure source of PAHs. Firefighter's personal exposure to PAHs at Portuguese fire stations were well below the existent occupational exposure limits. Also, the quantified concentrations of post-shift urinary 1-hydroxypyrene in all firefighters were clearly lower than the benchmark level (0.5MUmol/mol) recommended by the American Conference of Governmental Industrial Hygienists. PMID- 26997335 TI - Getting to know the person behind the illness - the significance of interacting with patients hospitalised in forensic psychiatric settings. AB - AIMS AND OBJECTIVES: To describe what nurses want to accomplish in relationships with patients who are hospitalised in forensic psychiatric settings. BACKGROUND: Relationships between staff and patients in forensic psychiatric settings should be grounded in trust and confidence, and the patients need opportunities for emotional reconciliation. However, relationships can be challenging for nurses, who sometimes distance themselves from patients' expressions of suffering. The role of forensic mental health nurses is nebulous, as are the prescriptives and the implementation of nursing practices. DESIGN: Qualitative descriptive design. METHODS: In-depth interviews with five nurses who all work in forensic psychiatric settings. RESULTS: We present a descriptive analysis of what nurses want to accomplish in relationships with patients who are hospitalised in forensic psychiatric settings. The results are presented in two main categories: (1) getting to know the person behind the illness and (2) making a difference. CONCLUSION: Care in forensic psychiatry needs to shift towards a more long-term view of the role of nursing, focusing less on the traditional and stereotypical identity of the productive nurse and more on the care given when nurses slow down and take the time to see the patients as individuals. Establishing trusting relationships with patients in forensic psychiatric settings is viewed as a less oppressive way to control patients and guide them in directions that are preferable for the nurses and for the society. RELEVANCE TO CLINICAL PRACTICE: Nurses may use simple strategies in their daily practice such as sitting on the sofa with patients to establish trust. We stress that nurses should abandon policing roles and custodial activities in favour of guiding principles that promote individual recovery, treatment and health-promoting care. PMID- 26997334 TI - Application of the new ESPEN definition of malnutrition in geriatric diabetic patients during hospitalization: A multicentric study. AB - BACKGROUND & AIMS: The European Society for Clinical Nutrition and Metabolism (ESPEN) recently provided new diagnosis criteria of malnutrition and called to confirm those criteria in specific populations. The aims of our study were 1) to determine the prevalence of malnutrition according to the new ESPEN definition in elder hospitalized diabetic patients, and 2) to evaluate whether this new diagnosis of malnutrition predicted clinical outcomes in these patients. METHODS: 1014 hospitalized diabetic patients (>=65 years) from 35 hospitals in Spain were screened for being at risk of malnutrition using the short version of the Mini Nutritional Assessment. Subsequently, at risk individuals were considered malnourished if they met at least one of the two options: 1) body mass index (BMI) < 18.5 kg/m2, or 2) unintentional weight loss >5% of their body weight with reduced BMI (<20 kg/m2 in subjects younger than 70 years or <22 kg/m2 in subjects older than 70 years). RESULTS: The new ESPEN definition, with MNA-SF as initial screening, identified 68 malnourished geriatric individuals with diabetes (6.73% of the cohort). Additionally, malnutrition lengthened the hospital stay, increased 2.7 times the odds of dying in hospital, and decreased to one third the odds of being discharged home. CONCLUSIONS: Our study confirms that the new ESPEN definition for the diagnosis of malnutrition is a reliable tool that is capable of predicting clinical outcomes in a large population of elder hospitalized individuals with diabetes. PMID- 26997336 TI - Single-cell RNA-seq reveals activation of unique gene groups as a consequence of stem cell-parenchymal cell fusion. AB - Fusion of donor mesenchymal stem cells with parenchymal cells of the recipient can occur in the brain, liver, intestine and heart following transplantation. The therapeutic benefit or detriment of resultant hybrids is unknown. Here we sought a global view of phenotypic diversification of mesenchymal stem cell cardiomyocyte hybrids and associated time course. Using single-cell RNA-seq, we found hybrids consistently increase ribosome components and decrease genes associated with the cell cycle suggesting an increase in protein production and decrease in proliferation to accommodate the fused state. But in the case of most other gene groups, hybrids were individually distinct. In fact, though hybrids can express a transcriptome similar to individual fusion partners, approximately one-third acquired distinct expression profiles in a single day. Some hybrids underwent reprogramming, expressing pluripotency and cardiac precursor genes latent in parental cells and associated with developmental and morphogenic gene groups. Other hybrids expressed genes associated with ontologic cancer sets and two hybrids of separate experimental replicates clustered with breast cancer cells, expressing critical oncogenes and lacking tumor suppressor genes. Rapid transcriptional diversification of this type garners consideration in the context of cellular transplantation to damaged tissues, those with viral infection or other microenvironmental conditions that might promote fusion. PMID- 26997337 TI - The effect of health transformation policies on the resident physicians' perception of the medical profession in Turkey. AB - Although the new changes in the health system in Turkey has resulted in positive implications with respect to the groups that use the healthcare services, it has been singled out for criticism by the professional associations because of its erosive consequences particularly for the medical profession as a whole. The purpose of this study is to explain how the health transformation policies and practices influenced the working conditions and perceptions of the resident physicians in Turkey with regard to the medical profession. A qualitative research design was employed, and the data was collected through document analysis and focus group interview. The common findings highlight that the new practices have had an aggravated effect on the working conditions of the resident physicians, which has resulted in several contentious issues. These include the increased workload, insufficient training and development, economic and social conditions and a heightened number of violent acts against physicians. Negatively, these influence the motivation of the physicians and their perception of the medical profession. This finding suggests that the medical profession is able to be studied as an appropriate case for the phenomenon of deprofessionalization. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26997338 TI - Cosmetics Europe compilation of historical serious eye damage/eye irritation in vivo data analysed by drivers of classification to support the selection of chemicals for development and evaluation of alternative methods/strategies: the Draize eye test Reference Database (DRD). AB - A thorough understanding of which of the effects assessed in the in vivo Draize eye test are responsible for driving UN GHS/EU CLP classification is critical for an adequate selection of chemicals to be used in the development and/or evaluation of alternative methods/strategies and for properly assessing their predictive capacity and limitations. For this reason, Cosmetics Europe has compiled a database of Draize data (Draize eye test Reference Database, DRD) from external lists that were created to support past validation activities. This database contains 681 independent in vivo studies on 634 individual chemicals representing a wide range of chemical classes. A description of all the ocular effects observed in vivo, i.e. degree of severity and persistence of corneal opacity (CO), iritis, and/or conjunctiva effects, was added for each individual study in the database, and the studies were categorised according to their UN GHS/EU CLP classification and the main effect driving the classification. An evaluation of the various in vivo drivers of classification compiled in the database was performed to establish which of these are most important from a regulatory point of view. These analyses established that the most important drivers for Cat 1 Classification are (1) CO mean >= 3 (days 1-3) (severity) and (2) CO persistence on day 21 in the absence of severity, and those for Cat 2 classification are (3) CO mean >= 1 and (4) conjunctival redness mean >= 2. Moreover, it is shown that all classifiable effects (including persistence and CO = 4) should be present in >=60 % of the animals to drive a classification. As a consequence, our analyses suggest the need for a critical revision of the UN GHS/EU CLP decision criteria for the Cat 1 classification of chemicals. Finally, a number of key criteria are identified that should be taken into consideration when selecting reference chemicals for the development, evaluation and/or validation of alternative methods and/or strategies for serious eye damage/eye irritation testing. Most important, the DRD is an invaluable tool for any future activity involving the selection of reference chemicals. PMID- 26997339 TI - Genetic variability, phylogenetic evaluation and first global report of Theileria luwenshuni, T. buffeli, and T. ovis in sheepdogs in Iran. AB - Theileriosis, caused by tick-borne hematozoan organisms, is a protozoan disease of domestic and wild mammals. The most phylo-molecular explorations of genus Theileria have been globally focused on the livestock and here are few investigations about canine Theileriosis. Twenty three and 52 blood samples were collected from sheepdogs and their owners, respectively, at different geographical foci of Mazandaran province (East, Central, and West regions), Northern Iran. To primary identify, the taken blood samples were fixed, stained, and surveyed by microscopic observation. DNA samples were extracted and amplified by polymerase chain reaction of 18s rRNA gene. The amplicons were directly sequenced to explore Theileria spp., and their heterogeneity traits. Sequencing and phylogenetic analyses revealed definitely the presence of Theileria luwenshuni, Theileria ovis, and Theileria buffeli (13 %) in sheepdog isolates, while no infection was found in dog owners. Consensus positions of T. luwenshuni showed two amino acid substitutions (haplotype diversity; 0.9) in codons 53 and 64 compared to wild type with identity 99.5 % and divergence 0.5-1.1, also one codon substitution (Hd; 0.875) found in T. buffeli with identity 97.6-99.5 % and divergence 0.5-2.5. No novel haplotype was identified in T. ovis isolate. The current results strengthen our understanding about genetic variability, molecular taxonomic status, and epidemiology of canine theileriosis among sheepdogs and their owners in Iran where there is no similar study. As well, it will facilitate the implementation of measures to control theileriosis in the region. Based on our knowledge, the current study presents the first report of T. luwenshuni, T. buffeli, and T. ovis infections in sheepdogs worldwide. PMID- 26997340 TI - Fine structure of uterus and non-functioning paruterine organ in Orthoskrjabinia junlanae (Cestoda, Cyclophyllidea). AB - Some cyclophyllidean cestodes provide protection for their eggs in the external environment by providing them with additional protective layers around the egg membranes. In attempting to examine such adaptations, the microanatomy and fine structure of the uterus of pregravid and gravid proglottids of the cyclophyllidean cestode Orthoskrjabinia junlanae, a parasite of mammals that inhabit a terrestrial but moist environment, were studied. In the initial stages of uterine development, developing embryos locate freely in the lumen of a saccate uterus that later partitions into chambers. Each chamber that forms encloses several embryos. The chambers are surrounded by muscle cells that synthesize extracellular matrix actively. The paruterine organs consist of stacks of flattened long outgrowths of muscular cells, interspersed with small lipid droplets. In the gravid proglottids, the size of paruterine organ increases and consists of flattened basal and small rounded apical parts separated by constrictions. The fine structure of the organ wall remains the same: sparse nuclei and stacks of flattened cytoplasmic outgrowths but internal invaginations or lumen in the paruterine organ are absent. Completely developed eggs remain localized in the uterus. Based on the comparative morpho-functional analysis of uterine and paruterine organs and uterine capsules in cestodes, we conclude that these non-functioning paruterine organ in O. junlanae is an example of an atavism. We postulate that the life cycle of the parasite, which infects mammals living in wet habitats, where threats of desiccation of parasite ova is reduced, has favoured a reversion to a more ancestral form of uterine development. PMID- 26997342 TI - Sensitivity and efficiency of selected coproscopical methods-sedimentation, combined zinc sulfate sedimentation-flotation, and McMaster method. AB - Coproscopical methods used in veterinary-parasitological diagnostics were validated according to their sensitivity (Se) and egg recovery rate [efficiency (Ef)]. Validation of the combined sedimentation-flotation method and the modified McMaster method was performed by using feces spiked with eggs of Ancylostoma caninum, Uncinaria stenocephala, Cooperia oncophora, cyathostomins, Ascaris suum, Toxascaris leonina, Toxocara canis, Trichuris vulpis, Moniezia expansa, and Anoplocephala perfoliata. For validation of the sedimentation method, Fasciola hepatica eggs were used. With the combined sedimentation-flotation method using ZnSO4 as flotation medium [specific gravity (SG) 1.30], 5 g fecal samples of all tested parasite species (concentration levels 1, 5, 10, 20, 40, 60, and 80 epg) were reproducibly detected "positive" (100 % Se) as of 80 epg. The Ef of the combined sedimentation-flotation method, defined as percentage of rediscovered eggs, revealed clear differences between parasites and showed the highest value for cyathostomins and the lowest for U. stenocephala and T. leonina eggs. The average Ef for all parasite species at 80 epg was 1.50 %. With the McMaster method (concentration levels 1, 30, 50, 80, 100, 500, and 1000 epg), all tested parasite species were detected reliably positive as of 500 epg with a mean Ef of 46.4 %. When evaluating the sedimentation method (concentration levels 1, 5, 10, 15, 20, 25, and 30 epg), F. hepatica eggs were reproducibly found in 5 g fecal samples as of 20 epg with 20.0 % Ef. The result that the combined zinc sulfate sedimentation-flotation method (SG 1.30) as flotation medium provides diagnostic certainty only as of 80 epg has to be considered at preventing zoonoses. If pet owners wish to prevent any zoonotic infection ("zero tolerance"), a monthly anthelminthic treatment should be advised instead of monthly fecal examinations. PMID- 26997341 TI - De novo RNA-Seq and functional annotation of Sarcoptes scabiei canis. AB - The transcriptomic data of Sarcoptes is still lacking in the public database due to the difficulty in extracting high-quality RNA from tiny mites with thick chitin. In this study, total RNA was extracted from live Sarcoptes mites for quality assessment, RNA-Seq, functional annotation, and coding region (CD) prediction and verification. The results showed that the sample JMQ-lngm was qualified for cDNA library construction. Firstly, Agilent 2100 detection showed that the RNA baseline was smooth and the 18S peak was single. Second, the Illumina platform generated 65.78M clean reads and 20,826 unigenes with 35.43M were assembled, occupying 62.98 % of the 56.26M genome. In total, 15,034 unigenes were annotated in seven functional databases. Finally, 13,122 CDs were detected in the 20,826 unigenes, of which 70 complete CDs were matched with Sarcoptes manually in non-redundant nucleotide (NT). Three CDs with indels >=10 bp were verified. Those results indicated that peritrophin sequences of JMQ-lngm missed 35 bp during the assembly; the pressure-sensitive sodium channel sequences of all the six Sarcoptes scabiei canis isolates were confirmed to be 90 bp shorter than that of a Sarcoptes scabiei hominis isolate; three introns remained in PH chlorine ion channel gating sequences of JMQ-lngm. Moreover, the allergen gene prediction for JMQ-lngm indicated that 61 unigenes were matched with 19 allergen genes of Dermatophagoides, of which Der 1, Der 3, Der 8, and Der 10 had been confirmed in NT. In conclusion, this study successfully completed the RNA-Seq and functional annotation of S. s. canis for the first time, which provides molecular data for future studies on the identification and pathogenic genes of Sarcoptidae. PMID- 26997343 TI - Dengue virus infection in a French traveller to the hilly region of Nepal in 2015: a case report. AB - BACKGROUND: Dengue viral infections are known to pose a significant risk during travel to tropical regions, but it is surprising to find dengue transmission in the hilly region of Nepal, which is over 1800mtr above sea level. CASE PRESENTATION: A 43-year-old Caucasian female traveler from France presented with fever and abdominal pain following a diarrheal illness while visiting the central hilly region of Nepal. Over the course of 9 days, she developed fever, body aches, and joint pain, with hemorrhagic manifestation. She was hospitalized in India and treated with supportive care, with daily monitoring of her platelets. An assessment by enzyme-linked immunosorbent assay showed that she was positive for dengue non-structural protein 1. Upon her return to France, dengue virus was confirmed by reverse transcriptase-polymerase chain reaction. CONCLUSION: The district where this dengue case was reported is in the hilly region of Nepal, neighboring the capital city Kathmandu. To the best of our knowledge, there has previously been no dengue cases reported from the district. This study is important because it aims to establish a potential region of dengue virus circulation not only in the tropics, but also in the subtropics as well, which in Nepal may exceed elevations of 1800mtr. This recent case report has raised alarm among concerned health personnel, researchers, and organizations that this infectious disease is now on the way to becoming established in a temperate climate. PMID- 26997344 TI - Dietary High Fluorine Alters Intestinal Microbiota in Broiler Chickens. AB - This study investigated the effects of dietary high fluorine on ileal and cecal microbiota in broiler chickens. Two hundred eighty 1-day-old broiler chickens were randomly assigned to four groups and raised for 42 days. The control group was fed a corn-soybean basal diet (fluorine 22.6 mg/kg). The other three groups were fed the same basal diet, but supplemented with 400, 800, and 1200 mg/kg fluorine (high fluorine groups I, II, and III), administered in the form of sodium fluoride. The microbiota of ileal and cecal digesta was assessed with plate counts and polymerase chain reaction-based denaturing gradient gel electrophoresis (PCR-DGGE). It was found that, compared with those in the control group, the counts of Lactobacillus spp. and Bifidobacterium spp. were markedly decreased (P < 0.01 or P < 0.05), whereas the counts of Escherichia coli and Enterococcus spp. were significantly increased (P < 0.01 or P < 0.05) in the high fluorine groups II and III. PCR-DGGE analysis showed that the number of DGGE bands, similarity, and Shannon index of ileal and cecal bacteria were markedly reduced in the high fluorine groups II and III from 21 to 42 days. Sequencing analysis revealed that the composition of the intestinal microbiota was altered in the high fluorine groups. In conclusion, dietary fluorine in the range of 800 1200 mg/kg obviously altered the bacterial counts, and the diversity and composition of intestinal microbiota in broiler chickens, a finding which implies that dietary high fluorine can disrupt the natural balance and structure of the intestinal microbiota. PMID- 26997345 TI - Validation of a Reading Assessment for Persons With Homonymous Hemianopia or Quadrantanopia. AB - OBJECTIVE: To preliminarily validate the Visual Skills for Reading Test (VSRT) for assessing reading performance in persons with homonymous hemianopia (HH) or quadrantanopia. DESIGN: Retrospective chart review. SETTING: University-based outpatient low vision rehabilitation center. PARTICIPANTS: Persons (N=38) with HH or quadrantanopia who completed the VSRT. INTERVENTIONS: Validation procedures included testing for equivalence of the 3 test versions, estimation of internal consistency reliability, and known-group comparison using VSRT results from previous studies of adults with normal vision and central field loss. MAIN OUTCOME MEASURES: Corrected reading rate, reading accuracy rate, type and number of reading errors, and completion time were recorded and evaluated. RESULTS: Cronbach alpha for the VSRT across all participants was .80, which indicated good internal consistency. A known-group comparison showed that persons with a visual field deficit read significantly slower than did normally sighted adults (t580=10.13; P<.0001). Persons with quadrantanopia read significantly faster than did persons with HH (t36=2.25; P=.03) or those with central field loss (t48=3.17; P=.0027). These findings confirmed that the VSRT correctly discriminated between groups in terms of reading performance. CONCLUSIONS: Preliminary validation results indicate that the VSRT demonstrates adequate evidence of reliability and validity to evaluate reading performance in adults with HH or quadrantanopia. PMID- 26997346 TI - A social paradigm in psychiatry - themes and perspectives. AB - AIMS: Psychiatry as science is underpinned by paradigms. Considering whether a social paradigm may help to advance the current state of psychiatry, the review provides a reference to the rich, but fragmented past of related initiatives in the history of psychiatry and a personal view of themes, challenges and perspectives of using a social paradigm in psychiatry. METHODS: Major themes are the evidence on social determinants of mental health; the value-based importance of integrating people with mental disorders in society; options to overcome the social isolation and improve the networks of psychiatric patients; utilising a systemic approach for interventions in families and communities; and understanding group and one-to-one treatments in psychiatry primarily as social interactions. Whilst all these themes open up perspectives for future action and/or research, there are also conceptual challenges through the limitations of the current construct of mental disorders and the dominating terminology. RESULTS: Initiatives for using a social paradigm in psychiatry may refer to important achievements in the past, but need to go beyond this and consider on going societal changes. CONCLUSION: Innovation may benefit from close collaboration with social sciences and humanities. PMID- 26997347 TI - Surfactant-Assisted Nanocrystalline Zinc Coordination Polymers: Controlled Particle Sizes and Synergistic Effects in Catalysis. AB - Different morphologies and particle sizes of two crystalline zinc-based coordination polymers (CPs), [Zn(pytz)H2 O]n (1; H2 pytz=2,6 bis(tetrazole)pyridine) and [Zn2 (pytz)2 4 H2 O] (2), from the bulk scale to the nanoscale, could be obtained under solvothermal conditions with different surfactants (polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) 2000) as templates. PVP and PEG 2000 could act as capping and structure-directing agents, respectively, to influence the growth of crystalline particles and control their sizes. CP 1 exhibits a two-dimensional framework with window-like units and 2 shows a bimetallic structure. Nanocrystalline 1 and 2 were used as heterogeneous catalysts to study how adjacent catalytic active sites synergistically effected their catalytic reactivities in the direct catalytic conversion of aromatic dinitriles into oxazolines. The results showed that 1 produced bis-oxazolines as the sole products, whereas 2 gave the mono-oxazolines as the major products under the same reaction conditions. PMID- 26997348 TI - HEPES is not suitable for fluorescence detection of HClO: a novel probe for HClO in absolute PBS. AB - HEPES is not suitable for fluorescence detection of HClO because it can be oxidized by HClO. A novel probe for HClO, which can selectively and sensitively detect HClO in absolute PBS, was developed on the basis of an oxidation reaction with an azo moiety. Furthermore, it works well in live mouse imaging. PMID- 26997350 TI - First Introduction of NiSe2 to Anode Material for Sodium-Ion Batteries: A Hybrid of Graphene-Wrapped NiSe2/C Porous Nanofiber. AB - The first-ever study of nickel selenide materials as efficient anode materials for Na-ion rechargeable batteries is conducted using the electrospinning process. NiSe2-reduced graphene oxide (rGO)-C composite nanofibers are successfully prepared via electrospinning and a subsequent selenization process. The electrospun nanofibers giving rise to these porous-structured composite nanofibers with optimum amount of amorphous C are obtained from the polystyrene to polyacrylonitrile ratio of 1/4. These composite nanofibers also consist of uniformly distributed single-crystalline NiSe2 nanocrystals that have a mean size of 27 nm. In contrast, the densely structured bare NiSe2 nanofibers formed via selenization of the pure NiO nanofibers consist of large crystallites. The initial discharge capacities of the NiSe2-rGO-C composite and bare NiSe2 nanofibers at a current density of 200 mA g(-1) are 717 and 755 mA h g(-1), respectively. However, the respective 100(th)-cycle discharge capacities of the former and latter are 468 and 35 mA h g(-1). Electrochemical impedance spectroscopy measurements reveal the structural stability of the composite nanofibers during repeated Na-ion insertion and extraction processes. The excellent Na-ion storage properties of these nanofibers are attributed to this structural stability. PMID- 26997351 TI - Impact of State Public Health Spending on Disease Incidence in the United States from 1980 to 2009. AB - OBJECTIVE: To understand the relationship between state-level spending by public health departments and the incidence of three vaccine preventable diseases (VPDs): mumps, pertussis, and rubella in the United States from 1980 to 2009. DATA SOURCES: This study uses state-level public health spending data from The Census Bureau and annual mumps, pertussis, and rubella incidence counts from the University of Pittsburgh's project Tycho. STUDY DESIGN: Ordinary least squares (OLS), fixed effects, and random effects regression models were tested, with results indicating that a fixed effects model would be most appropriate model for this analysis. PRINCIPAL FINDINGS: Model output suggests a statistically significant, negative relationship between public health spending and mumps and rubella incidence. Lagging outcome variables indicate that public health spending actually has the greatest impact on VPD incidence in subsequent years, rather than the year in which the spending occurred. Results were robust to models with lagged spending variables, national time trends, and state time trends, as well as models with and without Medicaid and hospital spending. CONCLUSION: Our analysis indicates that there is evidence of a significant, negative relationship between a state's public health spending and the incidence of two VPDs, mumps and rubella, in the United States. PMID- 26997352 TI - Evolutionary patterns of shape and functional diversification in the skull and jaw musculature of triggerfishes (Teleostei: Balistidae). AB - The robust skull and highly subdivided adductor mandibulae muscles of triggerfishes provide an excellent system within which to analyze the evolutionary processes underlying phenotypic diversification. We surveyed the anatomical diversity of balistid jaws using Procrustes-based geometric morphometric analyses and a phylomorphospace approach to quantifying morphological transformation through evolution. We hypothesized that metrics of interspecific cranial shape would reveal patterns of phylogenetic diversification that are congruent with functional and ecological transformation. Morphological landmarks outlining skull and adductor mandibulae muscle shape were collected from 27 triggerfish species. Procrustes-transformed skull shape configurations revealed significant phylogenetic and size-influenced structure. Phylomorphospace plots of cranial shape diversity reveal groupings of shape between different species of triggerfish that are mostly consistent with phylogenetic relatedness. Repeated instances of convergence upon similar cranial shape by genetically disparate taxa are likely due to the functional demands of shared specialized dietary habits. This study shows that the diversification of triggerfish skulls occurs via modifications of cranial silhouette and the positioning of subdivided jaw adductor muscles. Using the morphometric data collected here as input to a biomechanical model of triggerfish jaw function, we find that subdivided jaw adductors, in conjunction with a unique cranial skeleton, have direct biomechanical consequences that are not always congruent with phylomorphospace patterns in the triggerfish lineage. The integration of geometric morphometrics with biomechanical modeling in a phylogenetic context provides novel insight into the evolutionary patterns and ecological role of muscle subdivisions in triggerfishes. J. Morphol. 277:737-752, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26997349 TI - Structural basis for germline antibody recognition of HIV-1 immunogens. AB - Efforts to elicit broadly neutralizing antibodies (bNAbs) against HIV-1 require understanding germline bNAb recognition of HIV-1 envelope glycoprotein (Env). The VRC01-class bNAb family derived from the VH1-2*02 germline allele arose in multiple HIV-1-infected donors, yet targets the CD4-binding site on Env with common interactions. Modified forms of the 426c Env that activate germline reverted B cell receptors are candidate immunogens for eliciting VRC01-class bNAbs. We present structures of germline-reverted VRC01-class bNAbs alone and complexed with 426c-based gp120 immunogens. Germline bNAb-426c gp120 complexes showed preservation of VRC01-class signature residues and gp120 contacts, but detectably different binding modes compared to mature bNAb-gp120 complexes. Unlike typical antibody-antigen interactions, VRC01-class germline antibodies exhibited preformed antigen-binding conformations for recognizing immunogens. Affinity maturation introduced substitutions increasing induced-fit recognition and electropositivity, potentially to accommodate negatively-charged complex-type N-glycans on gp120. These results provide general principles relevant to the unusual evolution of VRC01-class bNAbs and guidelines for structure-based immunogen design. PMID- 26997353 TI - Sensitivity to censored-at-random assumption in the analysis of time-to-event endpoints. AB - Over the past years, significant progress has been made in developing statistically rigorous methods to implement clinically interpretable sensitivity analyses for assumptions about the missingness mechanism in clinical trials for continuous and (to a lesser extent) for binary or categorical endpoints. Studies with time-to-event outcomes have received much less attention. However, such studies can be similarly challenged with respect to the robustness and integrity of primary analysis conclusions when a substantial number of subjects withdraw from treatment prematurely prior to experiencing an event of interest. We discuss how the methods that are widely used for primary analyses of time-to-event outcomes could be extended in a clinically meaningful and interpretable way to stress-test the assumption of ignorable censoring. We focus on a 'tipping point' approach, the objective of which is to postulate sensitivity parameters with a clear clinical interpretation and to identify a setting of these parameters unfavorable enough towards the experimental treatment to nullify a conclusion that was favorable to that treatment. Robustness of primary analysis results can then be assessed based on clinical plausibility of the scenario represented by the tipping point. We study several approaches for conducting such analyses based on multiple imputation using parametric, semi-parametric, and non-parametric imputation models and evaluate their operating characteristics via simulation. We argue that these methods are valuable tools for sensitivity analyses of time-to event data and conclude that the method based on piecewise exponential imputation model of survival has some advantages over other methods studied here. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26997355 TI - Infant feeding: beyond the nutritional aspects. AB - OBJECTIVE: To draw attention to the importance of interaction between caregiver and child during feeding and the influence of parenting style on dietary habit formation. SOURCE OF DATA: A search was performed in the PubMed and Scopus databases for articles addressing responsive feeding; the articles considered most relevant by the authors were selected. SYNTHESIS OF DATA: The way children are fed is decisive for the formation of their eating habits, especially the strategies that parents/caregivers use to stimulate feeding. In this context, responsive feeding has been emphasized, with the key principles: feed the infant directly and assist older children when they already eat on their own; feed them slowly and patiently, and encourage children to eat but do not force them; if the child refuses many types of foods, experiment with different food combinations, tastes, textures, and methods of encouragement; minimize distractions during meals; and make the meals an opportunity for learning and love, talking to the child during feeding and maintaining eye contact. It is the caregiver's responsibility to be sensitive to the child's signs and alleviate tensions during feeding, and make feeding time pleasurable; whereas it is the child's role to clearly express signs of hunger and satiety and be receptive to the caregiver. CONCLUSION: Responsive feeding is very important in dietary habit formation and should be encouraged by health professionals in their advice to families. PMID- 26997354 TI - Behavioral and neural correlates of emotional development: typically developing infants and infants of depressed and/or anxious mothers. AB - OBJECTIVES: To describe the main findings of studies of behavioral and neural correlates regarding the development of facial emotion processing during the first year of life in typically developing infants and infants of depressed and/or anxious mothers. SOURCES: Comprehensive, non-systematic review of the literature on studies about individual differences in facial emotion processing by newborns and infants over the first year of life. SUMMARY OF THE FINDINGS: Maternal stress related to depression and anxiety has been associated to atypical emotional processing and attentional behaviors in the offspring. Recent neurophysiological studies using electroencephalogram and event-related potentials have begun to shed light on the possible mechanisms underlying such behaviors. CONCLUSIONS: Infants of depressed and/or anxious mothers have increased risk for several adverse outcomes across the lifespan. Further neurobehavioral investigations and the promotion of clinical and developmental research integration might eventually contribute to refining screening tools, improving treatment, and enabling primary prevention interventions for children at risk. PMID- 26997356 TI - Fidgety movements - tiny in appearance, but huge in impact. AB - OBJECTIVES: To describe fidgety movements (FMs), i.e., the spontaneous movement pattern that typically occurs at 3-5 months after term age, and discuss its clinical relevance. SOURCES: A comprehensive literature search was performed using the following databases: MEDLINE/PubMed, CINAHL, The Cochrane Library, Science Direct, PsycINFO, and EMBASE. The search strategy included the MeSH terms and search strings ('fidgety movement*') OR [('general movement*') AND ('three month*') OR ('3 month*')], as well as studies published on the General Movements Trust website (www.general-movements-trust.info). SUMMARY OF THE DATA: Virtually all infants develop normally if FMs are present and normal, even if their brain ultrasound findings and/or clinical histories indicate a disposition to later neurological deficits. Conversely, almost all infants who never develop FMs have a high risk for neurological deficits such as cerebral palsy, and for genetic disorders with a late onset. If FMs are normal but concurrent postural patterns are not age-adequate or the overall movement character is monotonous, cognitive and/or language skills at school age will be suboptimal. Abnormal FMs are unspecific and have a low predictive power, but occur exceedingly in infants later diagnosed with autism. CONCLUSIONS: Abnormal, absent, or sporadic FMs indicate an increased risk for later neurological dysfunction, whereas normal FMs are highly predictive of normal development, especially if they co-occur with other smooth and fluent movements. Early recognition of neurological signs facilitates early intervention. It is important to re-assure parents of infants with clinical risk factors that the neurological outcome will be adequate if FMs develop normally. PMID- 26997357 TI - Non-Fullerene Polymer Solar Cells Based on Alkylthio and Fluorine Substituted 2D Conjugated Polymers Reach 9.5% Efficiency. AB - Non-fullerene polymer solar cells (PSCs) with solution-processable n-type organic semiconductor (n-OS) as acceptor have seen rapid progress recently owing to the synthesis of new low bandgap n-OS, such as ITIC. To further increase power conversion efficiency (PCE) of the devices, it is of a great challenge to develop suitable polymer donor material that matches well with the low bandgap n-OS acceptors thus providing complementary absorption and nanoscaled blend morphology, as well as suppressed recombination and minimized energy loss. To address this challenge, we synthesized three medium bandgap 2D-conjugated bithienyl-benzodithiophene-alt-fluorobenzotriazole copolymers J52, J60, and J61 for the application as donor in the PSCs with low bandgap n-OS ITIC as acceptor. The three polymers were designed with branched alkyl (J52), branched alkylthio (J60), and linear alkylthio (J61) substituent on the thiophene conjugated side chain of the benzodithiophene (BDT) units for studying effect of the substituents on the photovoltaic performance of the polymers. The alkylthio side chain, red shifted absorption down-shifted the highest occupied molecular orbital (HOMO) level and improved crystallinity of the 2D conjugated polymers. With linear alkylthio side chain, the tailored polymer J61 exhibits an enhanced JSC of 17.43 mA/cm(2), a high VOC of 0.89 V, and a PCE of 9.53% in the best non-fullerene PSCs with the polymer as donor and ITIC as acceptor. To the best of our knowledge, the PCE of 9.53% is one of the highest values reported in literature to date for the non-fullerene PSCs. The results indicate that J61 is a promising medium bandgap polymer donor in non-fullerene PSCs. PMID- 26997358 TI - Low oxygen tension favored expansion and hematopoietic reconstitution of CD34(+) CD38(-) cells expanded from human cord blood-derived CD34(+) Cells. AB - Oxygen tension is an important factor that regulates hematopoietic stem cells (HSCs) in both in vivo hematopoietic microenvironment and ex vivo culture system. Although the effect of oxygen tension on ex vivo expansion of HSCs was extensively studied, there were no clear descriptions on physiological function and gene expression analysis of HSCs under different oxygen tensions. In this study, the effects of oxygen tension on ex vivo expansion characteristics of human umbilical cord blood (UCB)-derived CD34(+) cells are evaluated. Moreover, the physiological function of expanded CD34(+) cells was assessed by secondary expansion ability ex vivo and hematopoietic reconstitution ability in vivo. Also, genetic profiling was applied to analyze the expression of genes related to cell function. It was found that low oxygen tension favored expansion of CD34(+) CD38( ) cells. Additionally, CD34(+) cells expanded under low oxygen tension showed better secondary expansion ability and reconstitution ability than those under atmospheric oxygen concentration. Finally, the genetic profiling of CD34(+) CD38( ) cells cultured under low oxygen tension was more akin to freshly isolated cells. These results collectively demonstrate that low oxygen tension was able to better maintain both self-renewal and hematopoietic reconstitution potential and may lay an experimental basis for clinical transplantation of HSCs. PMID- 26997359 TI - Effects of High Salt Intake on Blood Pressure and Cardiovascular Disease: The Role of COX Inhibitors. AB - Sodium has a bidirectional effect on blood pressure (BP) and cardiovascular disease (CVD). High sodium intake increases both BP and CVD, whereas low sodium intake decreases them. The significance of this association has been debated for years, mostly due to the inconsistency of data, but recently it has been revived due to new evidence about the harmful effects of sodium. Recent studies have indicated that high sodium intake was associated with an increase in BP and CVD, which in 2010 was estimated to have accounted for 1.65 million deaths worldwide. Based on this evidence, the American Heart Association has issued a Science Advisory statement regarding the significance of high sodium intake in relation to the incidence of hypertension and CVD. In addition to high sodium intake, experimental studies have shown that the coadministration of nonsteroidal anti inflammatory drugs further aggravates the harmful effects of high sodium intake. The interrelationship of high sodium intake and nonsteroidal anti-inflammatory drugs will be discussed in this commentary. PMID- 26997361 TI - Indigenous Australians with non-small cell lung cancer or cervical cancer receive suboptimal treatment. AB - BACKGROUND: Lung cancer and cervical cancer are higher in incidence for Indigenous Australians and survival is worse compared with non-Indigenous Australians. Here we aim to determine if being Indigenous and/or other factors are associated with patients receiving "suboptimal treatment" compared to "optimal treatment" according to clinical guidelines for two cancer types. METHODS: Data were collected from hospital medical records for Indigenous adults diagnosed with cervical cancer and non-small cell lung cancer (NSCLC) and a frequency-matched comparison group of non-Indigenous patients in the Queensland Cancer Registry between January 1998 and December 2004. The two cancer types were analyzed separately. RESULTS: A total of 105 women with cervical cancer were included in the study, 56 of whom were Indigenous. Indigenous women had higher odds of not receiving optimal treatment according to clinical guidelines (unadjusted OR 7.1; 95% CI, 1.5-33.3), even after adjusting for stage (OR 5.7; 95% CI, 1.2-27.3). Of 225 patients with NSCLC, 198 patients (56% Indigenous) had sufficient information available to be analyzed. The odds of receiving suboptimal treatment were significantly higher for Indigenous compared to non-Indigenous NSCLC patients (unadjusted OR 1.9; 95% CI, 1.0-3.6) and remained significant after adjusting for stage, comorbidity and age (adjusted OR 2.1; 95% CI, 1.1 4.1). CONCLUSIONS: The monitoring of treatment patterns and appraisal against guidelines can provide valuable evidence of inequity in cancer treatment. We found that Indigenous people with lung cancer or cervical cancer received suboptimal treatment, reinforcing the need for urgent action to reduce the impact of these two cancer types on Indigenous people. PMID- 26997360 TI - On the relationship between cellular and hemodynamic properties of the human brain cortex throughout adult lifespan. AB - Establishing baseline MRI biomarkers for normal brain aging is significant and valuable for separating normal changes in the brain structure and function from different neurological diseases. In this paper for the first time we have simultaneously measured a variety of tissue specific contributions defining R2* relaxation of the gradient recalled echo (GRE) MRI signal in human brains of healthy adults (ages 22 to 74years) and related these measurements to tissue structural and functional properties. This was accomplished by separating tissue (R2t(*)) and extravascular BOLD contributions to the total tissue specific GRE MRI signal decay (R2(*)) using an advanced version of previously developed Gradient Echo Plural Contrast Imaging (GEPCI) approach and the acquisition and post-processing methods that allowed the minimization of artifacts related to macroscopic magnetic field inhomogeneities, and physiological fluctuations. Our data (20 healthy subjects) show that in most cortical regions R2t(*) increases with age while tissue hemodynamic parameters, i.e. relative oxygen extraction fraction (OEFrel), deoxygenated cerebral blood volume (dCBV) and tissue concentration of deoxyhemoglobin (Cdeoxy) remain practically constant. We also found the important correlations characterizing the relationships between brain structural and hemodynamic properties in different brain regions. Specifically, thicker cortical regions have lower R2t(*) and these regions have lower OEF. The comparison between GEPCI-derived tissue specific structural and functional metrics and literature information suggests that (a) regions in a brain characterized by higher R2t(*) contain higher concentration of neurons with less developed cellular processes (dendrites, spines, etc.), (b) regions in a brain characterized by lower R2t(*) represent regions with lower concentration of neurons but more developed cellular processes, and (c) the age-related increases in the cortical R2t(*) mostly reflect the age-related increases in the cellular packing density. The baseline GEPCI-based biomarkers obtain herein could serve to help distinguish age-related changes in brain cellular and hemodynamic properties from changes which occur due to the neurodegenerative diseases. PMID- 26997362 TI - Shape-Dependent Interactions of Palladium Nanocrystals with Hydrogen. AB - Elucidation of the nature of hydrogen interactions with palladium nanoparticles is expected to play an important role in the development of new catalysts and hydrogen-storage nanomaterials. A facile scaled-up synthesis of uniformly sized single-crystalline palladium nanoparticles with various shapes, including regular nanocubes, nanocubes with protruded edges, rhombic dodecahedra, and branched nanoparticles, all stabilized with a mesoporous silica shell is developed. Interaction of hydrogen with these nanoparticles is studied by using temperature programmed desorption technique and by performing density functional theory modeling. It is found that due to favorable arrangement of Pd atoms on their surface, rhombic dodecahedral palladium nanoparticles enclosed by {110} planes release a larger volume of hydrogen and have a lower desorption energy than palladium nanocubes and branched nanoparticles. These results underline the important role of {110} surfaces in palladium nanoparticles in their interaction with hydrogen. This work provides insight into the mechanism of catalysis of hydrogenation/dehydrogenation reactions by palladium nanoparticles with different shapes. PMID- 26997363 TI - Understanding taxanes in prostate cancer; importance of intratumoral drug accumulation. AB - BACKGROUND: Resistance to docetaxel is common in metastatic castration-resistant prostate cancer (mCRPC) and may be caused by sub-therapeutic intratumoral drug concentrations. Cabazitaxel demonstrated survival benefit in docetaxel-pretreated and docetaxel-refractory patients. In this study, we investigated whether the superior antitumor activity of cabazitaxel in mCRPC is explained by higher intratumoral cabazitaxel levels. Since recent studies suggest a reduced efficacy of docetaxel following treatment with novel androgen receptor (AR)-targeted agents, we also investigated taxane efficacy in an enzalutamide-resistant tumor model. METHODS: Intratumoral concentrations of docetaxel and cabazitaxel were correlated with antitumor activity in docetaxel-naive, docetaxel-resistant, and enzalutamide-resistant patient-derived xenografts (PDXs) of prostate cancer. RESULTS: Intratumoral drug levels were negatively related to intrinsic and acquired resistance to docetaxel. Also, the observed stronger antitumor activity of cabazitaxel was associated with increased cumulative exposure and higher intratumoral of cabazitaxel concentrations in all PDXs. CONCLUSIONS: The superior antitumor activity of cabazitaxel in docetaxel- and enzalutamide-resistant tumors can be partly attributed to higher intratumoral drug concentrations. Especially for patients who are intrinsically resistant to docetaxel resulting from suboptimal intratumoral docetaxel concentrations, cabazitaxel may be the preferred chemotherapeutic agent. Prostate 76:927-936, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26997364 TI - Rewarded visual items capture attention only in heterogeneous contexts. AB - Reward is known to affect visual search performance. Rewarding targets can increase search performance, whereas rewarding distractors can decrease search performance. We used subcomponents of the N2pc in the event-related EEG, the NT (target negativity) and ND /PD (distractor negativity/positivity), in a visual search task to disentangle target and distractor processing related to reward. The visual search task comprised homogeneous and heterogeneous contexts in which a target and a colored distractor were embedded. After each correct trial, participants were given a monetary reward that depended on the color of the distractor. We found longer response times for displays with high-reward distractors compared to displays with low-reward distractors, indicating reward induced interference, however, only for heterogeneous contexts. The NT component, indicative of attention deployment to the target, showed that target selection was impaired by high-reward distractors, regardless of the context homogeneity. Processing of distractors was not affected by reward in homogeneous contexts. In heterogeneous contexts, however, high-reward distractors were more likely to capture attention (ND ) and required more effort to be suppressed (PD ) than low reward distractors. In sum the results showed that, despite the fact that target selection is impaired by high-reward distractors in both homogeneous and heterogeneous background contexts, high-reward distractors capture attention only in scenarios that foster attentional capture. PMID- 26997365 TI - Understanding cochleate formation: insights into structural development. AB - Understanding the structure and the self-assembly process of cochleates has become increasingly necessary considering the advances of this drug delivery system towards the pharmaceutical industry. It is well known that the addition of cations like calcium to a dispersion of anionic lipids such as phosphatidylserines results in stable, multilamellar cochleates through a spontaneous assembly. In the current investigation we have studied the intermediate structures generated during this self-assembly of cochleates. To achieve this, we have varied the process temperature for altering the rate of cochleate formation. Our findings from electron microscopy studies showed the formation of ribbonlike structures, which with proceeding interaction associate to form lipid stacks, networks and eventually cochleates. We also observed that the variation in lipid acyl chains did not make a remarkable difference to the type of structure evolved during the formation of cochleates. More generally, our observations provide a new insight into the self-assembly process of cochleates based on which we have proposed a pathway for cochleate formation from phosphatidylserine and calcium. This knowledge could be employed in using cochleates for a variety of possible biomedical applications in the future. PMID- 26997366 TI - Modulation of human monocyte/macrophage activity by tocilizumab, abatacept and etanercept: An in vitro study. AB - Tocilizumab, etanercept and abatacept are biological drugs used in the therapy of Rheumatoid Arthritis (RA). Their mechanism of action is well documented but their direct effects on human monocytes/macrophages have not been fully investigated. The objective of this study was to evaluate in vitro the influence of these drugs on monocytes/macrophages from healthy volunteers. Human monocytes were isolated from healthy anonymous volunteers and cultured as such or differentiated to monocyte-derived macrophages (MDMs). The effect of tocilizumab, etanercept and abatacept (at concentrations similar to those in plasma of patients) on superoxide anion production, matrix metalloproteinase-9 (MMP-9) gene expression and activity, Peroxisome Proliferator-Activated Receptor (PPAR)gamma expression and cell phenotype was evaluated. Exposure of monocytes/macrophages to tocilizumab, etanercept or abatacept resulted in a significant decrease of the PMA-induced superoxide anion production. Interestingly, the expression of PPARgamma was significantly increased only by tocilizumab, while etanercept was the only one able to significantly reduce MMP-9 gene expression and inhibit the LPS-induced MMP-9 activity in monocytes. When etanercept and abatacept were added to the differentiating medium, both significantly reduced the amount of CD206(+)MDM. This study demonstrates that etanercept, abatacept and tocilizumab affect differently human monocytes/macrophages. In particular, the IL-6 antagonist tocilizumab seems to be more effective in inducing an anti inflammatory phenotype of monocytes/macrophages compared to etanercept and abatacept, also in light of the up-regulation of PPARgamma whose anti inflammatory effects are well recognised. PMID- 26997367 TI - Targeting the 19S proteasomal subunit, Rpt4, for the treatment of colon cancer. AB - Deregulation of the ubiquitin-proteasome pathway has been frequently observed in a number of malignancies. Using quantitative Western blotting of normal and matched tumour tissue, we here identified a significant increase in the 19S proteasome subunit Rpt4 in response to chemoradiation in locally advanced rectal cancer patients with unfavourable outcome. We therefore explored the potential of Rpt4 reduction as a therapeutic strategy in colorectal cancer (CRC). Utilizing siRNA to down regulate Rpt4 expression, we show that silencing of Rpt4 reduced proteasomal activity and induced endoplasmic reticulum stress. Gene silencing of Rpt4 also inhibited cell proliferation, reduced clonogenic survival and induced apoptosis in HCT-116 colon cancer cells. We next developed a cell penetrating peptide-based nanoparticle delivery system to achieve in vivo gene silencing of Rpt4. Administration of Rpt4 siRNA nanoparticles reduced tumour growth and improved survival in a HCT-116 colon cancer xenograft tumour model in vivo. Collectively, our data suggest that inhibition of Rpt4 represents a novel strategy for the treatment of CRC. PMID- 26997368 TI - Schisantherin A suppresses interleukin-1beta-induced inflammation in human chondrocytes via inhibition of NF-kappaB and MAPKs activation. AB - Osteoarthritis is a degenerative joint disease that is characterized by the inflammation of synovium. Schisantherin A (SchA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been shown to have anti inflammatory activity. The aim of this study was to investigate the anti inflammatory effects of SchA on interleukin-1beta (IL-1beta)-stimulated human osteoarthritis chondrocytes. Human osteoarthritis chondrocytes were pretreated with SchA 1h before IL-1beta treatment. The effects of SchA on NO, PGE2, iNOS, COX-2, and TNF-alpha production were detected in this study. The production of MMP-1, MMP3, MMP13 were measured by ELISA. The expression of NF-kappaB and MAPKs were detected by western blotting. Our results showed that SchA inhibited IL 1beta-induced NO, PGE2, and TNF-alpha production in a dose-dependent manner. Moreover, IL-1beta-induced MMP1, MMP3, and MMP13 expression were significantly inhibited by treatment of SchA. In addition, SchA significantly inhibited IL 1beta-induced NF-kappaB and MAPKs activation. Taken together, these results suggest that SchA exhibits anti-inflammatory effects against IL-1beta-stimulated chondrocytes by blocking NF-kappaB and MAPKs signaling pathways. PMID- 26997369 TI - Evidence for neural contribution to islet effects of DPP-4 inhibition in mice. AB - It has been suggested that neural mechanisms may contribute to effects of the incretin hormones, and, therefore, also to the effects of dipeptidyl peptidase (DPP-4) inhibition. We therefore examined whether muscarinic mechanisms are involved in the stimulation of insulin secretion by DPP-4 inhibition. Fasted, anesthetized mice were given intraperitoneal saline or the muscarinic antagonist atropine (5mg/kg) before duodenal glucose (75mg/mouse), with or without the DPP-4 inhibitor NVPDPP728 (0.095mg/mouse), or before intravenous glucose (0.35g/kg) with or without co-administration with GLP-1 or glucose-dependent insulinotropic polypeptide (GIP) (both 3nmol/kg). Furthermore, isolated islets were incubated (1h) in 2.8 and 11.1mM glucose, with or without GIP or GLP-1 (both 100nM), in the presence or absence of atropine (100uM). Duodenal glucose increased circulating insulin and this effect was potentiated by DPP-4 inhibition. The increase in insulin achieved by DPP-4 inhibition was reduced by atropine by approximately 35%. Duodenal glucose also elicited an increase in circulating intact GLP-1 and GIP and this was augmented by DPP-4 inhibition, but these effects were not affected by atropine. Atropine did also not affect the augmentation by GLP-1 and GIP on glucose-stimulated insulin secretion from isolated islets. Based on these findings, we suggest that muscarinic mechanisms contribute to the stimulation of insulin secretion by DPP-4 inhibition through neural effects induced by GLP-1 and GIP whereas neural effects do not affect the levels of GLP-1 or GIP or the islet effects of the two incretin hormones. PMID- 26997370 TI - Pinacidil-postconditioning is equivalent to ischemic postconditioning in defeating cardiac ischemia-reperfusion injury in rat. AB - Ischemic postconditioning (IPO) had been reported as a promising method against myocardial ischemia-reperfusion (I/R) injury, but IPO was later proved with poor clinical benefit. In this study, we compared the protective effects of pinacidil postconditioning (PPO) and IPO against myocardial I/R injury. Langendorff rat hearts were randomly assigned to one of the following groups (n=8 each): Control group, I/R group (40min ischemia and 60min reperfusion), IPO group (6 successive cycles of 10s reperfusion per 10s occlusion before fully reperfusion), PPO group (perfused with 50MUM pinacidil for 5min before reperfusion). Heart performance, infarct size and mitochondrial respiratory function were evaluated, and target genes/proteins of well-known Nuclear Factor-E2 Related Factor 2 (Nrf2) were assessed. Both IPO and PPO preserved heart function and myocardial ultrastructure at the end of reperfusion (all P<0.05 vs. I/R). The expression of Nrf2, NADH quinone oxidoreductase-1 (NQO1), heme oxygenase 1 (HO-1) and superoxide dismutase 1 (SOD1) were similarly increased after IPO and PPO treatment (all P<0.05 vs. I/R). PPO exerted solid effect in defeating cardiac ischemia-reperfusion injury in rat. PMID- 26997372 TI - Molecular characterization of a c-type lysozyme from the desert locust, Schistocerca gregaria (Orthoptera: Acrididae). AB - Lysozymes are bacteriolytic peptides that are implicated in the insect nonspecific innate immune responses. In this study, a full-length cDNA encoding a c-type lysozyme from Schistocerca gregaria (SgLys) has been cloned and characterized from the fat body of immune-challenged 5(th) instar. The deduced mature lysozyme is 119 amino acid residues in length, has a calculated molecular mass of 13.4 kDa and an isoelectric point (Ip) of 9.2. SgLys showed high identities with other insect lysozymes, ranging from 41.5% to 93.3% by BLASTp search in NCBI. Eukaryotic in vitro expression of the SgLys ORF (rSgLys) with an apparent molecular mass of ~16 kDa under SDS-PAGE is close to the calculated molecular weight of the full-length protein. rSgLys displayed growth inhibitory activity against Gram-negative and Gram-positive bacteria. 3D structure modeling of SgLys, based on comparison with that of silkworm lysozyme, and sequence comparison with the helix-loop-helix (alpha-hairpin) structure of hen egg white lysozyme (HEWL) were employed to interpret the antibacterial potencies. Phylogenetic alignments indicate that SgLys aligns well with insect c-type lysozymes that expressed principally in fat body and hemocytes and whose role has been defined as immune-related. Western blot analysis showed that SgLys expression was highest at 6-12 h post-bacterial challenge and subsequently decreased with time. Transcriptional profiles of SgLys were determined by semi quantitative RT-PCR analysis. SgLys transcript was upregulated at the highest level in fat body, hemocytes, salivary gland, thoracic muscles, and epidermal tissue. It was expressed in all developmental stages from egg to adult. These data indicate that SgLys is a predominant acute-phase protein that is expressed and upregulated upon immune challenge. PMID- 26997373 TI - Averting the legacy of kidney disease - Focus on childhood. AB - World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID- 26997371 TI - Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. AB - DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 * 10(-6)). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability. PMID- 26997374 TI - Pregnancy after renal transplantation: Effects on mother, child, and renal graft function. AB - The aim of this study was to report our experience of pregnancy in renal transplant (RT) patients and its medium and long-term effects on the renal graft as well as the maternal fetal complications. We studied 21 pregnancies in 12 RT patients with mean age of 29.9 +/- 5.3 years. The mean duration of RT to 1 st pregnancy was 42 (21-68.5) months and the median follow-up period was 112.5 (138 165) months. The pregnancy was planned in 28.6% of the cases. At the time of the diagnosis of the pregnancy, all the patients were maintained on corticosteroids and cyclosporine, 14.3% of the patients were on mycophenolate mofetil, and 71.4% of the patients were on azathioprine. The high blood pressure was present before the pregnancy in 33.3% of the patients. During pregnancy, proteinuria appeared in 20% of the cases, urinary tract infection in 33.3%, and preeclampsia in 5%. Anemia was present in all the patients during pregnancy. The doses of cyclosporine were increased during pregnancy. The mean term of delivery was 37 +/ 2 weeks. Premature delivery was observed in 19% of the cases, fetal death in utero in 10%, and abortion in 15%. The number of living children was 16, with a mean birth weight of 3014 +/- 515 g; the weight was lower than 2500 g in three (15%) cases. In the long-term follow-up, we noticed two cases of acute rejection related to patients' noncompliance, and four cases of chronic allograft nephropathy, without a switch to dialysis. We conclude that pregnancy in RT patients requires multidisciplinary care because of the increased risks of maternal and fetal complications. Each pregnancy needs to be planned; all parameters have to be studied and evaluated in order to allow for optimization of outcome and minimization of complications. PMID- 26997375 TI - Serum magnesium level and vascular stiffness in children with chronic kidney disease on regular hemodialysis. AB - Chronic kidney disease (CKD) patients have a high prevalence of vascular calcifications, and cardiovascular disease is the leading cause of death in this population. Magnesium (Mg) depletion may be the missing link between multiple cardiovascular risk factors and the development of atherosclerosis. In this study, we aimed to assess the relationship between serum Mg levels and vascular stiffness in children with CKD on regular hemodialysis (HD). The study included 25 children with CKD on regular HD in our center; the study included also 25 healthy children age-and sex-matched as a control group. Serum Mg levels were measured, and Doppler ultrasound assessment of the intima-media thickness (IMT) and the peak systolic velocities (PSVs) of the main arteries including the (aorta, carotid, and femoral) arteries were recorded in the study patients. There were significantly lower serum Mg levels in children on regular HD than in the controls (1.7 +/- 0.43 mg/dL vs. 2.31 +/- 0.12 mg/dL, respectively, P = 0.001). There was a significant increase in the aorta and carotid IMT in the study group than in the controls (0.45 +/- 0.07 mm vs. 0.40 +/- 0.09 mm; 0.98 +/- 0.57 mm vs. 0.55 +/- 0.1 mm, P = 0.034 and 0.001, respectively), whereas there were no significant differences regarding the PSV of the carotid, aorta, and femoral arteries between the study patients and the controls (P >0.05). A negative correlation was found between serum Mg level with aortic IMT (AIMT) (r = -0.682; P = 0.000). In addition, a significant negative correlation was found between the AIMT with systolic and diastolic blood pressure (r = 0.447, P = 0.025, 0.472, P = 0.017), respectively. We conclude that lower serum Mg levels were associated with vascular calcification in chronic HD children. Confirmation of our results warrants further study. PMID- 26997377 TI - Influence of nutritional education on hemodialysis patients' knowledge and quality of life. AB - To determine the effects of educational instructions on hemodialysis patients' knowledge and quality of life (QOL), we studied 99 patients randomly assigned to control and experimental groups after participation in a pretest exam. The two groups were not significantly different in terms of demographic composition. The instrument used in this study was a questionnaire regarding patients' knowledge and the standard questionnaire to assess QOL for end-stage renal disease (ESRD) patients. Then, intervention (nutritional education) was conducted in the experimental group lasting for 12 weeks. After 16 weeks, a post test regarding subjects' knowledge on dietary instructions and their QOL were as conducted. There was no significant difference in QOL score and knowledge score before and after intervention in the control group, but there was a significant difference in the experimental group. In addition, after the intervention, the difference in knowledge and QOL score persisted between the two groups. The results of this study supported the positive effects of educational program on patients' knowledge and QOL among ESRD patients. It is recommended that dietary instruction be included in all educational programs to improve ESRD patients' QOL. PMID- 26997376 TI - Blood pressure measurement in hemodialysis: The importance of the measurement technique. AB - Systemic arterial hypertension contributes to the high cardiovascular morbidity in hemodialysis (HD) patients, but the accuracy of blood pressure (BP) measurement in this population has not been well studied. To evaluate the agreement between BP measurement using the routine measurement technique (usual method) and the technique recommended by the VII Joint (standard method). This cross-sectional study enrolled 124 patients in a single center who had undergone dialysis for more than three months and were 18 years of age or older. The BP was verified at the start of dialysis by the nursing team (usual method) and by the researchers (standard method). The agreement between the systolic and diastolic BP (SBP and DBP) measurements was tested by the Bland-Altman analysis. A difference in BP measurement higher than +/-5 mm Hg was considered clinically significant. The studied group had a mean age of 53.2 years. The average difference between routine and standard BP measurement was -6 mm Hg for SBP (limits of agreement: -40.1-28 mm Hg; P <0.001) and -5.6 mm Hg for DBP (limits of agreement: -33.1-21.8 mm Hg; P <0.001). A clinically significant difference in BP measured by both methods was observed in 69.4% of the patients for SBP and in 61.3% for DBP. The disagreement between the results of different BP measurement methods in HD patients was significant and the BP was underestimated using the usual BP method. BP measurement standardization should be encouraged to avoid errors in diagnosis and therapy. PMID- 26997378 TI - Effect of Vitamin B12 supplementation on serum homocysteine in patients undergoing hemodialysis: A randomized controlled trial. AB - Clinical studies have shown that hyper-homocysteinemia is a potent independent risk factor for cardiovascular diseases, and many different methods have been investigated for lowering it in hemodialysis (HD) patients. Our study investigated the effect of Vitamin B 12 supplementation on serum homocysteine levels in these patients. This randomized trial was conducted on 140 HD patients. They were randomly distributed by lottery method into two groups: intervention and control. In the intervention group, 100 MUg/mL of Vitamin B 12 was intravenously injected two times a week, for eight weeks. No intervention was performed in the control group. Serum levels of homocysteine, hemoglobin (Hb), and hematocrit (Hct) were measured at the beginning and again after eight weeks (2 months) of treatment. About 91% of the patients had hyperhomocysteinemia (serum homocysteine >15 MUmol/L). The median baseline levels of serum homocysteine in the intervention and control groups were 31.9 and 26.9 MUmol/L, respectively (P = 0.1). After eight weeks, the median homocysteine level reduced significantly in the Vitamin B 12 group to 22.2 versus 28.4 MUmol/L in control group (P = 0.006). The mean Hb and Hct also changed significantly during our study (12.3 vs. 11.4 g/dL; P = 0.003 and 37.9 vs. 35.3%; P = 0.02, respectively). Our results demonstrated the existence of a statistical negative relationship between Vitamin B 12 and serum levels of homocysteine. Detailed investigations with larger sample sizes and longer-term use of Vitamin B 12 are recommended. PMID- 26997380 TI - A comparison of the quality of life of the patients undergoing hemodialysis versus peritoneal dialysis and its correlation to the quality of dialysis. AB - Over the years, there has been a steady increase in the number of patients requiring dialysis. However, no consensus exists between choosing either hemodialysis (HD) or peritoneal dialysis (PD) as the preferred method of dialysis for patients. In this study, we have compared the quality of life of the patients undergoing either HD or PD. This cross-sectional study was performed in the dialysis center of the Noor and Saint Ali Asghar University Hospital in Isfahan, Iran in 2012. Forty-six patients who underwent PD (28 males and 18 females) and 46 similar patients undergoing HD (26 males and 20 females) were compared. A standardized Persian version of the short form-36 (SF-36) tool was used to assess the quality of life and to assess the quality of dialysis weekly Kt/V in patients undergoing PD and single random Kt/V sampling in HD patients were assessed. Patients undergoing PD reported higher scores in physical functioning. The lowest scores in both groups were reported in mental health section. In physical functioning section, physical role functioning section and overall score of the SF-36 tool, PD patients reported significantly higher scores compared to the HD patients (P <0.05). There was no significant difference between the qualities of the dialysis in the two patient groups. Aspects of quality of life such as physical functioning, physical role functioning, bodily pain, general health perceptions, and overall score were significantly different between the two groups. If these results are substantiated by subsequent longitudinal studies, then the choice of dialysis could be better guided in patients by the quality of life issues. PMID- 26997379 TI - The relationship between total mass and blood supply of parathyroid glands and their secretion of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism. AB - Characteristics of parathyroid glands usually determined by ultrasonography such as its total weight or volume might be a good indicator for the induction or suppression of parathyroid hormone (PTH) secretion from these glands. In the present study, we investigated the relationship between the volume and blood supply grade of the parathyroid glands, and its PTH secretion. Study subjects included 52 consecutive patients with the secondary hyperparathyroidism undergoing maintenance hemodialysis therapy referred to dialysis wards of the Imam Khomeini and Amiralam University Hospitals in Tehran. Serum intact PTH (i PTH) was measured by an ELISA assay. The parathyroid glands characteristics were identified by ultrasonography that was performed simultaneously with blood collection. Parathyroid blood flows were evaluated by power-Doppler color imaging. There was no significant correlation between the total mass of the glands and serum concentration of i-PTH. No significant correlations were also observed between both total central and peripheral parathyroid glands blood flow and serum i-PTH level. Dialysis duration and serum alkaline phosphatase were significantly correlated in a positive manner with i-PTH level. Furthermore, serum level of i-PTH was not correlated with the total signals of glands blood flow in a multivariable linear regression analysis. Serum secreted i-PTH level might not be predictable by a total mass of parathyroid glands as well as their blood supply. PMID- 26997381 TI - A modified peritoneal dialysis catheter with a new technique: Farewell to catheter migration. AB - To evaluate the efficacy our new, three-cuff peritoneal dialysis (PD) catheter, with the low-entry technique and to study its impact on catheter survival and mechanical and infectious complications, we prospectively used it in 36 incident PD patients and compared the results with those of conventional double-cuff PD Tenckhoff catheters with the classic approach used in 37 patients. The study was carried out at our university hospital over a period of 18 months. At the end of the study, significantly higher survival rate was observed with the use of new catheter compared with the conventional two-cuff Tenckhoff catheter, 91.7% and 73%, respectively, (P <0.01); the difference in catheter survival was due to a lower incidence (P < 0.01) of catheter-tip migration and a lower incidence (P <0.01) of peritonitis. Dialysis fill and drain times were significantly shorter and Kt/V was better with our new catheter. In conclusion, the study suggests superiority of our new catheter and our new technique over the conventional one in terms of catheter survival. This is due to less incidences of catheter tip migration in addition to lower peritonitis rates. Dialysis adequacy was better because of shortened fill and drain time. PMID- 26997382 TI - Multinational observational study on clinical practices and therapeutic management of mineral and bone disorders in patients with chronic kidney disease stages 4, 5, and 5D: The OCEANOS study. AB - Our aim is to assess the current clinical practices in monitoring and treatment patterns of chronic kidney disease (CKD)-mineral bone disorder and the degree to which these practices met the kidney disease improving global outcome (KDIGO) guidelines. This was an international, multi-center, cross-sectional, observational study in adult patients diagnosed with CKD Stages 4, 5, and 5D. Patients were enrolled from Middle East, South Asia, Eurasia, and Africa; patients with estimated glomerular filtration rate >=30 mL/min/1.73 m(2) or with any medical/surgical conditions precluding their participation were excluded. Frequency of measurements, levels of serum calcium (Ca), phosphorus and parathormone (parathyroid hormone [PTH], and presence vascular/valvular calcification were recorded. Of the 2250 patients enrolled, data on 2247 patients were evaluated. Overall, only a small percentage of patients met all three target KDIGO ranges of serum Ca, phosphorus, and PTH (13.7% [95% confidence interval: 12.0; 15.4], with a higher proportion among CKD Stage 5D patients (14.8%) than CKD Stage 4 and 5 (5.6%) patients. Majority (84.3%) of the patients received treatment with phosphorous binders, of whom 85.5% received Ca-based phosphate binders. Overall, 57.0% of patients received Vitamin D treatment with a similar frequency among patients with CKD Stages 4, 5, and 5D. Over half (65.7%) of the patients were screened for vascular/valvular calcification; of these, 58.8% had >=1 calcification. Diabetes status, P, PTH, and low density lipoprotein cholesterol had significant impact on the prescription pattern of phosphorous binders. The current practices for the management of bone and mineral metabolism in CKD patients in the study region fall far short of meeting the KDIGO target range. PMID- 26997383 TI - Prognostic significance of C1q deposition in serial biopsies for predicating the long-term outcome in patients with proliferative lupus nephritis. AB - Lupus nephritis (LN) is characterized by a highly variable clinical course. It has been reported that histopathologic lesions are risk factors for the progression of LN. The aim of this study is to investigate the relationship among the co-deposition of C1q, clinicopathological features, and renal outcomes in patients with LN. The clinical and histological parameters were studied in patients with International Society of Nephrology/Renal Pathology Society Class III or IV LN, who underwent two kidney biopsies. The patients were divided into two groups based on the glomerular C1q deposits: C1q-positive and C1q-negative. The impact of C1q status and longterm renal outcome on the doubling of serum creatinine and the rate of remission in the two groups were further investigated. Fifty-three patients had pure proliferative nephritis and 37.7% of these had a co deposition of C1q. Doubling of serum creatinine was observed in 25% of patients with C1q-positive and 24.2% of patients with C1q-negative deposits. There was no difference between the two groups in terms of achieving complete or partial remission. The renal survival in the two groups was similar (P = 0.75). Upon repeat biopsy, the persistence of C1q positivity was associated with a poor outcome (P = 0.007). C1q deposition in the glomerulus in the baseline biopsy was not associated with a poor renal outcome or severe pathologic features in patients with proliferative LN. However, the persistence of C1q positivity in repeat kidney biopsy is associated with a poor renal outcome. PMID- 26997384 TI - Utility of saliva as a sample to assess renal function and estimated glomerular filtration rate. AB - Diagnosis of renal diseases by assessing renal parameters in saliva. Biochemical investigations using serum form important component of monitoring patients with renal disease. Utility of saliva, in diagnosis and monitoring of patients with renal disease and for calculation of estimated glomerular filtration rate (eGFR), was studied. Sixty patients with renal disease and sixty ageand sex-matched healthy controls were studied. Urea, creatinine, sodium, potassium, uric acid, calcium, and phosphorus were measured in both serum and saliva. eGFR was calculated using salivary creatinine. Data were expressed as mean +/- standard deviation. Comparison and correlation between groups were assessed by Student's t test and Pearson correlation, respectively. Bland-Altman plot, mountain plot, and intra-class correlation coefficient were used to test agreement. A P <0.05 was considered statistically significant. Statistical analysis was done using Microsoft excel spreadsheets, Medcalc Version 10.0, and SPSS version 11.5. Salivary levels of urea, creatinine, uric acid, sodium, potassium, and phosphorus were higher in patients compared to controls. Potassium and phosphorus levels were higher (P = 0.001) and creatinine, sodium, calcium, and uric acid levels were lower (P = 0.001) in saliva compared to serum in both patients and controls. Positive correlation was observed between serum and salivary urea and creatinine (P < 0.0001). eGFR values calculated from salivary creatinine showed good agreement with those calculated form serum creatinine. Salivary urea (>6 mmol/L) and creatinine (>14.6 MUmol/L) and eGFR calculated from salivary creatinine can be used to identify patients with renal disease. PMID- 26997385 TI - Accuracy of GFR estimation formula in determination of glomerular filtration rate in kidney donors: Comparison with 24 h urine creatinine clearance. AB - To determine the accuracy of estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD), Cockcroft-Gault (CG), and chronic kidney disease epidemiology (CKD-EPI) formulas in potential kidney donors compared with 24-h urine creatinine clearance, we studied 207 potential live kidney donors in our center. There were 126 (60.9%) males and 81 (39.1%) females. Male:female ratio was 1.6:1. The age of the donors ranged from 18-58 years, with mean age of 35.30 +/- 9.23 years and most of the individuals were below 40 years of age. The body mass index (BMI) was calculated and venous blood samples were obtained for the measurement of serum creatinine and every study participant was instructed to collect 24-h urine. GFR was calculated based on 24-h urine creatinine clearance and the formulas. The accuracy of GFR estimation formula was taken as positive if the GFR calculated by the formulas and urine creatinine clearance fell between 90-120 mL/min/1.73 m(2). The accuracy of the MDRD formula was 48.8% and the CG formula was 41.5% whereas the accuracy of the CKD-EPI formula was 78.2%. The accuracy of the eGFR using the MDRD formula was significantly higher in males than females (57.9% vs. 33.3% P = 0.001), while there was no statistically significant difference in the eGFR between them in case of the use of the CG and the CKD-EPI formulas. BMI and obesity had no effect on the accuracy of eGFR by the use of the different formulas. The performance of GFR estimation formulas was sub optimal and these either underestimated and/or over-estimated the GFR in healthy subjects. CKD-EPI is closer to 24 -h urinary creatinine clearance in the calculation of eGFR. However, none of the eGFR formulas can be used in renal transplant donors because of their low accuracy, and 24-h urine creatinine clearance should be used for evaluation of the GFR in this population. PMID- 26997386 TI - Restless legs syndrome in hemodialysis patients. AB - Restless legs syndrome (RLS) is a neurological disorder characterized by uncomfortable sensation of paresthesia in legs that subsequently causes involuntary and continuous movement of the lower limbs, especially at rest. Its prevalence in hemodialysis is more than that in the general population. Different risk factors have been suggested for RLS. We studied the prevalence and risk factors of RLS in 137 hemodialysis patients followed up at our center. The patients completed at least three months on dialysis and fulfilled four criteria for the diagnosis of RLS. We compared the patients with and without RLS, and the odds ratios (ORs) were estimated by the logistic regression models. The prevalence of RLS was 36.5% in the study patients. Among the variables, diabetes was the only predicting factor for the development of RLS. The diabetic patients may be afflicted with RLS 2.25 times more than the non-diabetics. Women developed severe RLS 5.23 times more than men. Neurodegeneration, decrease in dopamine level, higher total oxidant status, and neuropathy in diabetic patients may explain the RLS symptoms. PMID- 26997387 TI - The effect of depression and anxiety on the performance status of end-stage renal disease patients undergoing hemodialysis. AB - Individuals who are diagnosed with end-stage renal disease (ESRD) undergo major changes in lifestyle. The present cross-sectional study was conducted to identify the relationship between patients who undergo hemodialysis (HD) and their performance status, and how it is influenced by the presence of the level of depression and anxiety. A total of 50 patients were recruited from HD centers in and around Chennai. The patients were screened using the General Health Questionnaire to screen for co-morbid psychiatric conditions. The patients were assessed for depression and anxiety, and their performance status was assessed using Beck's Depression Inventory, Beck's Anxiety Inventory, and Karnofsky Performance Status. The study findings indicate that there is a positive correlation between anxiety and depression in ESRD patients. The findings also indicated that depression and anxiety are positively correlated with the performance status of ESRD patients. The duration on, as well as the frequency of dialysis, also correlated with the performance status of ESRD patients. It can be concluded that anxiety and depression are prevalent among ESRD patients and that they interfere with the performance status; additionally, duration on dialysis also interferes with performance status. Addressing depression and anxiety can help in enhancing the patient's performance status. PMID- 26997388 TI - Outcome of patients with multiple myeloma and renal failure on novel regimens. AB - Renal involvement occurs in 20-40% of newly diagnosed multiple myeloma (MM) patients, and diagnosis of myeloma is frequently made after investigation for unexplained renal disease. This is a retrospective study between 2006 and 2013 in which 57 consecutive patients seen at the Nephrology Unit with diagnosis of MM were enrolled. MM was diagnosed for the first time because of renal dysfunction and/or proteinuria in these patients. The mean age of the patients (65% male) was 58.3 +/- 12.7 years. The median baseline serum creatinine was 3.5 mg/dL (1.4 14.5). Anemia (hemoglobin <12 g/dL) was noted in 88% and hypercalcemia (calcium >10.5 mg/dL) in 35% of patients. Early hemodialysis was started in 28 patients (49%). Thalidomide plus dexamethasone (16% on bortezomib) were the main therapeutic regimens. Three patients (5%) underwent autologous stem cell transplantation. Twenty-six patients (45.6%) died during a median follow-up of 25 months (1-90). The mean age of patients who died was significantly higher than the age in patients who were alive (62.2 +/- 12.7 vs. 55.2 +/- 11.9 years, respectively; P = 0.037). Early hemodialysis had no significant effect on mortality rate. The one-, three and five year patient survival was 71%, 54%, and 41%, respectively. The median overall survival of patients was 50 months. Prolonged patient survival can be expected in myeloma patients with renal failure or on dialysis by applying novel therapeutic agents. PMID- 26997389 TI - Five years renal transplantation data: Single-center experience from Iraq. AB - Renal transplantation is the treatment of choice for patients with end-stage renal disease. In Iraq, renal transplantation started in 1973 and has continued until now with live donor transplantation, since deceased donor transplant program is not approved as yet. Long-term transplant data are still scarce. The aim of our study is to present data on transplantation and medical follow-up at one year and, survival analysis at one, three and five years. A total of 250 renal transplantations were performed at the Nephrology and Renal Transplantation Center, Baghdad between January 2009 and January 2014. It is a living donor, blood group compatible donor program. All patients received triple immunosuppression (calcineurine inhibitor, mycophenolate mofetil or mycophenolic acid, and steroid). The Kaplan-Meier method was used to determine the survival rate. There were 92 live related donors, 143 unrelated donors, and 15 spouse donors. The mean age was 34.07 +/- 12.2 years. The one-year graft survival for related and unrelated donor transplants was 98.9% and 91.8%, respectively. Graft survival was lower (82.9%) in recipients with acute rejection episodes. The patient survival at one-year was 94%. The three-year graft and patient survival was 91% and 90%, respectively, and five-year survival for grafts and patients was 87.1% and 88%, respectively. The outcome of the renal transplantation in Iraq is improving. Long-term patient follow-up needs more meticulous attention. The development of renal transplant registry is critical for future planning. Moreover, renal transplantation practice in Iraq needs more social, religious, and governmental support. PMID- 26997390 TI - Prevalence and determinants of microalbuminurea among type 2 diabetes mellitus patients, Baghdad, Iraq, 2013. AB - Microalbuminuria (MAU) is an early marker of diabetic nephropathy (DN), which accounts for a significant reduction in life expectancy of diabetic patients. The progression of DN from the appearance of clinical proteinuria to end stage renal failure is usually irreversible. Increased levels of urinary albumin secretion may represent a more generalized vascular damage. This is the first study conducted in Iraq to determine the prevalence and potential risk factors of MAU among Type 2 diabetes mellitus (T2DM) patients. A cross-sectional study was conducted on a systematic random sample of 224 eligible T2DM patients aged 25-64 years attending a DM clinic in Baghdad. A questionnaire was developed to gather basic and clinical data, besides anthropometric measurements, and laboratory assessment of lipid profile, HbA1c, serum creatinine, albumin, and microalbumin/creatinin in urine. MAU was defined as albumin/creatinine ratio 30 300 mg/g on two occasions. Only 36 cases (16.1%) had MAU. A statistical significant association found between MAU and educational level (P = 0.009), family history of hypertension (P = 0.024) and DN (P = 0.013), history of hypertension (P = 0.001), duration of angiotensin-converting-enzyme inhibitor drug intake in hypertensive patients (P = 0.001), body mass index (BMI) (P = 0.014), and waist to hip ratio (P = 0.006). Logistic regression analyses revealed two independent risk factors influencing MAU: diastolic blood pressure [odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.007-1.118] and BMI (OR = 1.17, 95% CI: 1.037-1.220). The prevalence of MAU is not low among DM patients. Mandatory screening of all DM patients and amelioration of the assigned significant risk factors are recommended. PMID- 26997391 TI - Graft function and nutritional parameters in stable postrenal transplant patients. AB - Bioelectrical impedance analysis (BIA) is a method for the assessment of nutritional status. We studied the effect of graft function on nutritional status in postrenal 45 transplant patients with borderline to good allograft function using BIA. The patients had a mean serum creatinine of 1.42 +/- 0.42 mg% and mean glomerular filtration rate (GFR) of 45.1 +/- 14.1 mL/min. Based on BIA-derived GFR, the patients were divided into two groups; group 1: borderline graft function GFR <40 mL/min and a mean of 27.34 +/- 9.1 mL/min and group 2: good graft function GFR >=40 mL/min and a mean of 51.60 +/- 9.16 mL/min. The patient data were compared with 30 healthy individuals. There was a significant difference between healthy controls and the posttransplant patients. There were significant differences between the study groups in body weight (P <0.01), serum creatinine (P <0.005), body mass index (BMI) (P <0.000), fat free mass (FFM) (P <0.003), fat mass (FM) (P <0.003), body cell mass (P <0.000), and dry weight (P <0.001). Group 1 had significantly lower body weight, BMI, FFM, FM, and dry weight, indicating poorer nutritional status compared with those in group 2. Based on phase angle, there were significant differences between group A (phase angle <4.0) and group B (phase angle >4.0) in extracellular water (P <0.015), intracellular water (P <0.002), plasma fluid (P <0.016), interstitial fluid (P <0.016), and body cell mass (P <0.024). Subjective global assessment (SGA) scores showed that transplant patients had normal nutritional status, but when compared with healthy individuals as assessed by BIA, there were significant differences in FM, FFM, and body cell mass. In conclusion, BIA was more sensitive to evaluate nutritional depletion than SGA in transplant patients with borderline. PMID- 26997392 TI - Identification of high-risk population and prevalence of kidney damage among asymptomatic central government employees in Delhi, India. AB - Chronic kidney disease (CKD) has attained epidemic proportions in India due to increased incidence of diabetes and hypertension (HTN). It was surmised that identification of only high-risk groups (HRGs) through a questionnaire would be sufficient to identify cases of kidney damage (KD). The study attempted to device a questionnaire to classify the subjects in to HRG and low-risk group (LRG) and assess the extent of early KD. The central government employees were classified into HRG and LRG based on "SCreening for Occult REnal Disease (SCORED)" and "EXTENDED" questionnaire formulated after addition of 10 more parameters apart from diabetes and HTN. Urine examination by dipstick, quantitative microalbumin, serum creatinine, and estimated glomerular filtration rate were assessed to determine KD. The data were analyzed for risk-group classification. Sensitivity was calculated based on the number of KD cases in the HRG. Of the 1104 employees screened, 58% and 42% were classified in HRG and LRG, respectively. There were 306 KD cases of whom, 65% were in the HRG. The sensitivity of the EXTENDED questionnaire to detect CKD was much higher (60%) compared to the SCORED questionnaire (25%). The prevalence of KD according to stage was: stage-1, 13.4%; stage-2, 9.9%; and late stages (3, 4, and 5), 4.5%. Microalbuminuria and dipstick positive proteinuria showed statistically higher proportion in the HRG (25% and 4.1%) than in the LRG (19% and 1%, respectively) (P <0.05). Although the EXTENDED questionnaire was more sensitive in detecting KD, only screening the high-risk population will leave behind 35% of KD cases. There is, therefore, a need for mass screening at regular intervals. PMID- 26997393 TI - Pattern of renal diseases in children: A developing country experience. AB - Spectrum of renal disease varies in different ethnic population, geographical location, and by environmental factors. The purpose of this study was to find out the clinical spectrum and occurrence of different pediatric renal diseases at a teaching hospital in the Eastern part of Nepal. All cases of renal diseases from one month to 15 years of age, attending the pediatric renal outpatient department and/or were admitted to the wards during the period of February 2012 to January 2013, were included in the study. Detailed clinical and laboratory evaluations were performed on all patients. Diseases were categorized as per standard definitions and managed with hospital protocols. Renal diseases accounted to be 206 cases (6.9%) of total annual pediatric admissions, of which (58%) were male and (42%) female. Acute glomerulonephritis (AGN) was the most common disorder (37.7%) followed by nephrotic syndrome (26.1%), urinary tract infection (21.3%), acute kidney injury (AKI) (17.9%), obstructive uropathy (1.9%), chronic kidney disease (CKD) (1.2%), and others. In AGN group, the most common cause was post infectious glomerulonephritis (PIGN) (32.9%) followed by lupus nephritis (4%) and Henoch-Schonlein purpura nephritis (0.8%). Urine culture was positive in (9.22%) and the most common organism was Escherichia coli (57.9%). The causes of AKI were urosepsis, septicemia, and AGN (18.9%) each, followed by dehydration (13.5%). Mortality was found in 5% of cases and the etiologies were AKI in (72.7%), PIGN (18.1%), and CKD (9%). Renal diseases are a significant problem among children and are one of the common causes of hospital admission. These patients need comprehensive services for early identification and management. PMID- 26997395 TI - Early recurrence of proliferative glomerulonephritis with monoclonal immunoglobulin deposits in a renal allograft. AB - Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMIDs) is a clinico-pathologic entity, the recurrence of which in the renal allograft has only recently been described. A 55-year-old male presented with rapid deterioration of renal function. Light microscopy showed membranoproliferative glomerulonephritis with kappa light chain restriction and only one sub-class of IgG. He subsequently underwent renal transplant. Two months later, he developed acute graft dysfunction. Renal biopsy showed a recurrence of the disease. Work up for multiple myeloma was positive. Membranoproliferative pattern of injury in the posttransplant setting has a wide range of differential diagnosis, PGNMID being one of them. PMID- 26997394 TI - Occurrence of double primary malignancies in an African renal transplant recipient. AB - A 63-year-old African male with end stage renal disease who received a renal transplantation from his daughter after successful treatment of hepatitis C virus, type 1 genotype developed metastatic Kaposi's sarcoma and subsequently adenocarcinoma of the prostate. He was successfully treated with chemotherapy and reduction of immunosuppression and switch over to rapamycin. PMID- 26997396 TI - Successful management of chylous ascites: A report of two cases. AB - Chylous ascites consists of the accumulation of chyle in the peritoneal cavity. Diagnosis is established by cytochemical analysis of the fluid revealing fat globules and high triglyceride content. The majority of cases are caused by pathology that interferes with abdominal retroperitoneal lymphatic drainage. We present two cases of postoperative chylous ascites, one following a bilateral nephrectomy, the other following orthotopic heart transplantation. Treatment is typically conservative with the aim to alleviate abdominal distension and reduce the flow of lymph into the mesenteric lymph nodes. Postsurgical chylous ascites has high cure rate with conservative therapy alone. Therapeutic paracentesis, diuretics, salt restriction, a high-protein, low-fat, mediumchain triglyceride diet, and parenteral nutrition are considered in chronic cases. The effects of longterm paracentesis on patients remains to be seen. In patients requiring renal replacement therapy, removal of chyle during peritoneal dialysis is often attempted. PMID- 26997397 TI - Cerebral venous thrombosis and secondary polycythemia in a case of nephrotic syndrome. AB - Cerebral venous thrombosis (CVT) and polycythemia are considered as rare and life threatening complications of nephrotic syndrome. We report an unusual combination of both these complications in a case of nephrotic syndrome due to minimal change disease that was treated successfully. There was prompt and complete remission of nephrotic syndrome with steroid therapy, concurrent with complete resolution of polycythemia and CVT. PMID- 26997398 TI - Asymptomatic pontine and extra-pontine lesions in a patient with end-stage renal disease. AB - Osmotic demyelination syndrome leading to central pontine/extra-pontine myelinolysis (CPM/EPM) occurs mainly in patients with history of alcohol abuse, malnourishment, following liver transplantation and less commonly, in association with other systemic diseases. Asymptomatic CPM/EPM is rare. Patients with end stage renal disease (ESRD) who develop CPM/EPM are usually symptomatic with florid neurologic manifestations. Herein, we present a patient with ESRD on maintenance hemodialysis who was incidentally detected to have pontine and extra pontine lesions suggestive of myelinolysis without any neurologic signs or symptoms. PMID- 26997399 TI - An unusual case of hematuria in a young female: renal artery embolism, mitral stenosis, and sinus rhythm. AB - Renal artery embolism (RAE) is an uncommon entity that is most often secondary to a cardiac source. Most reported cases have been in patients with underlying atrial fibrillation (AF), and occurrence of RAE, especially in patients with valvular heart disease, and sinus rhythm is very rare. We describe an unusual case of a young female who presented with sudden onset right flank pain, vomiting, anorexia, and hematuria, and was found to have thrombotic occlusion of the distal right renal artery. Although she denied any previous cardiac history, detailed cardiovascular examination revealed the presence of severe rheumatic mitral stenosis without any evidence of AF or left atrial clot. She was initially managed conservatively using low molecular weight heparin followed by oral anticoagulation with resolution of symptoms. A successful balloon mitral valvotomy was performed six weeks later. The patient is asymptomatic at her last follow-up of six months with preserved renal function. In symptomatic patients, clinicians need to consider the possibility of RAE even in patients of valvular heart disease with underlying sinus rhythm. Appropriate management of the underlying cardiac condition is imperative since embolism may be recurrent leading to compromise of renal function, if left untreated. PMID- 26997400 TI - Takayasu arteritis associated with severe renovascular hypertension. AB - Takayasu arteritis (TA) is an inflammatory process frequently associated with stenosis and obliteration of the aorta and its primary branches. We report a 16 year-old girl in whom TA manifested mainly with a sudden decrease in visual acuity and severe arterial hypertension in both legs. Bilateral radial pulses were absent. Ultrasound showed renal size asymmetry and raised the possibility of renal artery stenosis. The diagnosis of TA was confirmed by computed tomography angiography, which showed a thickened abdominal aortic wall and narrowing of its lumen. In addition, occlusions of left renal artery and of both left and right subclavian arteries were observed. Hypertension was hardly under control by a combination of three antihypertensive drugs. The outcome was favorable with corticosteroids alone with regression of the clinical signs, disappearance of inflammation, and control of hypertension. PMID- 26997401 TI - Quadriparesis due to Gitelman's syndrome diagnosed with thiazide diuretic test response. AB - Gitelman's syndrome is characterized by hypocalciuria, severe hypomagnesemia, and prominent muscular involvements such as fatigue, weakness, cramps, and tetany. It is due to mutations in the thiazide sensitive NaCl co-transporter in the distal convoluted tubule. The administration of thiazide diuretics may induce a subnormal increase of urinary Cl(-) excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less than normal Cl(-) is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Thus, we report a case of Gitelman's syndrome presenting with quadriparesis diagnosed by using thiazide clearance test. PMID- 26997402 TI - Posterior reversible encephalopathy syndrome in a hypertensive patient with renal failure. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinical and neuroimaging entity characterized by headache, visual field deficits, changes in mentation and seizures, and by typical neuro-imaging features such as areas of sub-cortical edema, occasionally cortical, involving predominantly the occipital and parietal lobes of both hemispheres. Hypertension, uremia, immunosuppressive drugs neurotoxicity, preeclampsia or eclampsia, renal disease, and sepsis are the most common etiologies of PRES. Less common, it has been described in the setting of autoimmune disease. We report a case of PRES which was associated with hypertensive crisis in a patient with renal failure. Antihypertensive therapy and hemodialysis resulted in complete recovery. PMID- 26997403 TI - Acute renal artery spasm during live kidney transplant surgery due to iatrogenic cause. PMID- 26997405 TI - Recurrent acute kidney injury in a young female: A rare presentation of ureteral endometriosis. PMID- 26997404 TI - WT1 mutations in steroid-resistant idiopathic nephrotic syndrome. PMID- 26997406 TI - Hypertension and diabetes remain the main causes of chronic renal failure in Fars Province, Iran 2013. PMID- 26997407 TI - The need to automate urinary creatinine ratios adjusted for the predicted daily creatinine excretion. PMID- 26997409 TI - Main group transformations. PMID- 26997413 TI - [Aggressions towards healthcare workers in Spain: Status a after the recent modification of the Spanish Penal Code]. PMID- 26997414 TI - Effect of different production techniques on bioactive compounds and antioxidant capacity of einkorn (Triticum monococcum L.) and durum (Triticum turgidum subsp. durum) bulgur. AB - BACKGROUND: The influence of cooking (traditional, microwave, autoclave) and drying techniques (microwave and hot air) on bioactive compounds in the production of einkorn and durum bulgur were investigated. Total phenolic content (TPC), total yellow pigment (TYP), total antioxidant capacity (DPPH* , ABTS*+ , FRAP), soluble free (SF), soluble conjugated (SC) and insoluble bound (IB) phenolic acid contents of the samples were determined. RESULTS: For both wheats, a significant amount of antioxidant capacity was preserved after bulgur production. TPC was found to be higher in einkorn but it was exposed to greater loss during bulgur production than durum. The amount of TYP was found to be two fold higher in einkorn than in durum. Ferulic acid was recorded as the most phenolic acid, and chlorogenic was the least phenolic acid in both wheats. The maximum loss during bulgur production was determined in the SC fraction for einkorn and in the SF fraction for durum. CONCLUSION: In respect of the results of the analysis, microwave cooking + hot air drying treatment could be favourable for bulgur production for both wheats. (c) 2016 Society of Chemical Industry. PMID- 26997416 TI - The geriatric management of frailty as paradigm of "The end of the disease era". AB - The sustainability of healthcare systems worldwide is threatened by the absolute and relative increase in the number of older persons. The traditional models of care (largely based on a disease-centered approach) are inadequate for a clinical world dominated by older individuals with multiple (chronic) comorbidities and mutually interacting syndromes. There is the need to shift the center of the medical intervention from the disease to the biological age of the individual. Thus, multiple medical specialties have started looking with some interest at concepts of geriatric medicine in order to better face the increased complexity (due to age-related conditions) of their average patient. In this scenario, special interest has been given to frailty, a condition characterized by the reduction of the individual's homeostatic reserves and increased vulnerability to stressors. Frailty may indeed represent the fulcrum to lever for reshaping the healthcare systems in order to make them more responsive to new clinical needs. However, the dissemination of the frailty concept across medical specialties requires a parallel and careful consideration around the currently undervalued role of geriatricians in our daily practice. PMID- 26997415 TI - Potential of mean force between like-charged nanoparticles: Many-body effect. AB - Ion-mediated interaction is important for the properties of polyelectrolytes such as colloids and nucleic acids. The effective pair interactions between two polyelectrolytes have been investigated extensively, but the many-body effect for multiple polyelectrolytes still remains elusive. In this work, the many-body effect in potential of mean force (PMF) between like-charged nanoparticles in various salt solutions has been comprehensively examined by Monte Carlo simulation and the nonlinear Poisson-Boltzmann theory. Our calculations show that, at high 1:1 salt, the PMF is weakly repulsive and appears additive, while at low 1:1 salt, the additive assumption overestimates the repulsive many-body PMF. At low 2:2 salt, the pair PMF appears weakly repulsive while the many-body PMF can become attractive. In contrast, at high 2:2 salt, the pair PMF is apparently attractive while the many-body effect can cause a weaker attractive PMF than that from the additive assumption. Our microscopic analyses suggest that the elusive many-body effect is attributed to ion-binding which is sensitive to ion concentration, ion valence, number of nanoparticles and charges on nanoparticles. PMID- 26997417 TI - Role of Barbed Sutures in Repairing Uterine Wall Defects in Laparoscopic Myomectomy: A Systemic Review and Meta-Analysis. AB - As an innovative technology barbed sutures have demonstrated clinical and surgical benefits in several specialties. The purpose of this study was to systemically review the available evidence on the application of barbed sutures in repairing the uterine wall defects in laparoscopic myomectomy and to compare with conventional suture in clinical safety and efficacy. Medline, Embase, and Cochrane Database of Systematic Reviews were used for a systematic electronic search of published literature. Studies were selected that evaluate barbed sutures in surgical treatment for patients with benign myomas eligible for laparoscopic myomectomy in comparison with conventional sutures. Depending on the heterogeneity, either a fixed-effects model or random-effects model was used in this meta-analysis. Continuous variable data were showed as standard mean difference (SMD) and weighted mean difference with 95% confidence interval (CI). A total of 7 studies (n = 484) met inclusion criteria. Compared with conventional sutures, barbed sutures demonstrated significant reductions in suturing time (SMD, -1.26; 95% CI, -1.85 to -.67; p < .001), operating time (SMD, -.64; 95% CI, -.83 to -.44; p < .001), intraoperative blood loss (SMD, -.43; 95% CI, -.79 to .06; p = .021), and postoperative hemoglobin drop (SMD, -.56; 95% CI, -1.01 to .11; p = .014). The result was numerically lower in the barbed suture group for hospital length of study, although there was no significant difference. This meta analysis demonstrates clear clinical advantages of time savings and blood loss reduction by using barbed sutures in close uterine wall defects in laparoscopic myomectomy compared with conventional sutures. Those benefits may reduce the surgical difficulty in laparoscopic myomectomy procedures. PMID- 26997408 TI - Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies. AB - BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 * 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 * 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings. PMID- 26997418 TI - Is CO2 Pneumoperitoneum Desufflation Triggering Factor of Postsurgical Oxidative Stress? PMID- 26997419 TI - Preemptive Local Anesthetic in Gynecologic Laparoscopy and Postoperative Movement Evoked Pain: A Randomized Trial. AB - STUDY OBJECTIVE: To evaluate whether preemptive local anesthetics injected into the trocar areas reduce postoperative movement-evoked pain within an enhanced recovery program (ERP) in laparoscopic gynecologic surgery. DESIGN: A randomized and double-blinded trial with parallel assignments (Canadian Task Force Classification I). SETTING: The study was conducted in the gynecologic department at the University Hospital of Stavanger, Stavanger, Norway. PATIENTS: Twenty-four women eligible for elective laparoscopic surgery for a benign indication within an ERP were included. INTERVENTIONS: The women were randomized to preemptive local injections of either 0.5% bupivacaine (intervention group) or 0.9% saline (control group) at each trocar site. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure of the study was movement-evoked pain 5 hours after surgery. The secondary outcome measures were pain at rest 2 and 5 hours after surgery and the use of rescue analgesics during the postoperative period. Pain was measured on a numeric rating scale of 0 to 10. Data were treated to a per-protocol analysis, and a p < .05 was considered significant. RESULTS: Twenty-three women completed the trial. The median score for movement-evoked pain 5 hours after surgery was significantly lower in the intervention group (1 vs. 3, p = .044). There was no difference in pain at rest after 2 and 5 hours and no difference in the requirement for rescue analgesics. CONCLUSION: Preemptive local anesthetics in the trocar areas are shown to be beneficial in laparoscopic gynecologic surgery within an enhanced recovery program. Movement-evoked pain is far more intense than pain at rest. PMID- 26997420 TI - Reply to "Is CO2 Pneumoperitoneum Desufflation Triggering Factor of Postsurgical Oxidative Stress?". PMID- 26997421 TI - Pinus sylvestris as a missing source of nitrous oxide and methane in boreal forest. AB - Boreal forests comprise 73% of the world's coniferous forests. Based on forest floor measurements, they have been considered a significant natural sink of methane (CH4) and a natural source of nitrous oxide (N2O), both of which are important greenhouse gases. However, the role of trees, especially conifers, in ecosystem N2O and CH4 exchange is only poorly understood. We show for the first time that mature Scots pine (Pinus sylvestris L.) trees consistently emit N2O and CH4 from both stems and shoots. The shoot fluxes of N2O and CH4 exceeded the stem flux rates by 16 and 41 times, respectively. Moreover, higher stem N2O and CH4 fluxes were observed from wet than from dry areas of the forest. The N2O release from boreal pine forests may thus be underestimated and the uptake of CH4 may be overestimated when ecosystem flux calculations are based solely on forest floor measurements. The contribution of pine trees to the N2O and CH4 exchange of the boreal pine forest seems to increase considerably under high soil water content, thus highlighting the urgent need to include tree-emissions in greenhouse gas emission inventories. PMID- 26997422 TI - Factors associated with radiologic progression of non-cystic fibrosis bronchiectasis during long-term follow-up. AB - BACKGROUND AND OBJECTIVE: Non-cystic fibrosis (CF) bronchiectasis is a chronic airway inflammatory disease, exhibiting a diverse array of clinical courses. The purpose of this study was to determine the factors that predict radiologic progression of non-CF bronchiectasis during a long-term follow-up. METHODS: We reviewed the electronic medical records that included pulmonary function test data from non-CF bronchiectasis patients, who were older than 18 years of age with a follow-up of computerized tomography for more than 5 years. The original Bhalla score was used to determine the radiologic severity of non-CF bronchiectasis. RESULTS: A total of 155 patients (mean age, 59.6 years; male, 45.2%) were included for the final analysis. The mean follow up time was 7.11 +/- 1.42 (5-10) years. The baseline Bhalla score was 9.52 +/- 3.14 (4-19), and the change of Bhalla score was 0.55 +/- 1.14 (-2 to 5). The Bhalla score was increased in 56 patients (36.1%) but not in 99 patients (63.9%). The Bhalla score change was significantly associated with the age at diagnosis (p = 0.037), body mass index (BMI, p = 0.012), chronic infection of Pseudomonas aeruginosa (p = 0.005) or isolation of nontuberculous mycobacterium (p = 0.042) in respiratory specimens. In a multivariate analysis, BMI and isolation of P. aeruginosa were significantly related with the Bhalla score change. CONCLUSION: The radiologic progression of non-CF bronchiectasis was associated with lower BMI and isolation of P. aeruginosa in respiratory specimens. PMID- 26997423 TI - Microencapsulation of rifampicin for the prevention of endophthalmitis: In vitro release studies and antibacterial assessment. AB - Rifampicin encapsulated microparticles were designed for intraocular injection after cataract surgery to prevent postoperative endophthalmitis. Microparticles were formulated by emulsification diffusion method using poly(lactic acid-co glycolic acid) (PLGA) as polymer in order to propose a new form of rifampicin that overcome its limitations in intraocular delivery. Depending on processing formulation, different types of microparticles were prepared, characterized and evaluated by in vitro release studies. Two types of microparticles were selected to get a burst release of rifampicin, to reach minimal inhibitory concentrations to inhibit 90% of Staphylococcus epidermidis mainly involved in postoperative endophthalmitis, combined with a sustained release to maintain rifampicin concentration over 24h. The antibacterial activity and antiadhesive property on intraocular lenses were evaluated on S. epidermidis. Microparticles, with a rapid rifampicin release profile, showed an effect towards bacteria development similar to free rifampicin over 48h. However, slow-release profile microparticles exhibited a similar antibacterial effect during the first 24h, and were able to destroy all the S epidermidis in the medium after 30h. The association of the two formulations allowed obtaining interesting antibacterial profile. Moreover, rifampicin-loaded microparticles have shown a very efficient anti-adherent effect of S. epidermidis on intraocular lenses at 24h. These results propose rifampicin microparticles as suitable for antibioprophylaxis of the postoperative endophthalmitis. PMID- 26997424 TI - A novel platform designed by Au core/inorganic shell structure conjugated onto MTX/LDH for chemo-photothermal therapy. AB - A novel platform making up of methotrexate intercalated layered double hydroxide (MTX/LDH) hybrid doped with gold nanoparticles (NPs) may have great potential both in chemo-photothermal therapy and the simultaneous drug delivery. In this paper, a promising platform of Au@PDDA-MTX/LDH was developed for anti-tumor drug delivery and synergistic therapy. Firstly, Au NPs were coated using Layer-by Layer (LbL) technology by alternate deposition of poly (diallyldimethylammonium chloride) (PDDA) and MTX molecules, and then the resulting core-shell structures (named as Au@PDDA-MTX) were directly conjugated onto the surface of MTX/LDH hybrid by electrostatic attraction to afford Au@PDDA-MTX/LDH NPs. Here MTX was used as both the agent for surface modification and the anti-tumor drug for chemotherapy. The platform of Au@PDDA-MTX/LDH NPs not only had a high drug loading capacity, but also showed excellent colloidal stability and interesting pH-responsive release profile. In vitro drug release studies demonstrated that MTX released from Au@PDDA-MTX/LDH was relatively slow under normal physiological pH, but it was enhanced significantly at a weak acidic pH value. Furthermore, the combined treatment of cancer cells by using Au@PDDA-MTX/LDH for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy. PMID- 26997425 TI - Development and potential application of an oral ColoPulse infliximab tablet with colon specific release: A feasibility study. AB - The monoclonal antibody infliximab is one of the cornerstones in the treatment of Crohn's disease. Local delivery of infliximab would be an alternative to overcome the inherent disadvantages of intravenous therapy. For this purpose 5mg infliximab tablets were developed. To stabilize the antibody during production and storage it was incorporated in a sugar glass containing the oligosaccharide inulin. To obtain colon-specific release a ColoPulse coating was applied. The tablets were stored for 16 months under different conditions based on ICH climatic zone I. PMID- 26997426 TI - AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution. AB - Alternating current electrospinning (ACES) capable to reach multiple times higher specific productivities than widely used direct current electrospinning (DCES) was investigated and compared with DCES to prepare drug-loaded formulations based on one of the most widespread polymeric matrix used for commercialized pharmaceutical solid dispersions, hydroxypropylmethylcellulose 2910 (HPMC). In order to improve the insufficient spinnability of HPMC (both with ACES and DCES) polyethylene oxide (PEO) as secondary polymer with intense ACES activity was introduced into the electrospinning solution. Different grades of this polymer used at as low concentrations in the fibers as 0.1% or less enabled the production of high quality HPMC-based fibrous mats without altering its physicochemical properties remarkably. Increasing concentrations of higher molecular weight PEOs led to the thickening of fibers from submicronic diameters to several microns of thickness. ACES fibers loaded with the poorly water-soluble model drug spironolactone were several times thinner than drug-loaded fibers prepared with DCES in spite of the higher feeding rates applied. The amorphous HPMC-based fibers with large surface area enhanced the dissolution of spironolactone significantly, the presence of small amounts of PEO did not affect the dissolution rate. The presented results confirm the diverse applicability of ACES, a novel technique to prepare fibrous drug delivery systems. PMID- 26997427 TI - Suppression of melanin synthesis by Americanin A in melan-a cells via regulation of microphthalmia-associated transcription factor. PMID- 26997428 TI - Ultrasonographic evaluation of Achilles tendon in children with flatfoot: A case control morphometric study. AB - PURPOSE: The purpose of this study was to investigate whether any relationships exist between the presence of flatfoot and ultrasonographic morphometric findings of Achilles tendon in children. MATERIALS AND METHODS: The study included 30 pediatric patients with a mean age of 11.96+/-2.44 (SD) years (range: 9-16 years) with flexible flatfoot and 29 healthy pediatric controls who were matched for age and served as a control group. Demographic data of both groups such as age, height and weight, and anthropometric measurements including leg length and, length and cross-sectional area of the Achilles tendon on ultrasonography were tabulated. Relationships between the cross-sectional area of Achilles tendon and flatfoot and the other parameters were searched for using backward multiple regression analysis. RESULTS: No associations between flatfoot and length and cross-sectional area of the Achilles tendon, age, height, leg and foot length were found. A negative correlation was found between the cross-sectional area of Achilles tendon and presence of flatfoot (Beta=-4.93, P=0.01) and age (Beta= 1.96, P=0.04). A positive correlation was found between the cross-sectional area of Achilles tendon and shoe size (Beta=2.13, P=0.007). CONCLUSIONS: Flatfoot, shoe size, age and weight must be kept in mind as a clue for a thinner Achilles tendon morphometry which can be a risk factor in lower limb pathologies. PMID- 26997429 TI - Do delays in radiology lead to breaches in the 4-hour rule? AB - AIM: To assess trends in medical imaging requests before and after the 4-hour rule commenced and to assess the imaging time component of emergency department (ED) length of stay (LOS). MATERIALS AND METHODS: Retrospective analysis of ED patients and imaging requests 1 year prior to and 3 years after implementation of the 4-hour rule (April to December for 2011-2014) was performed at a single adult tertiary referral Level 1 trauma hospital with Level 6 ED. Logistic regression was used to evaluate trends in the number of ED patient presentations, patient triage categories, and imaging requests for these patients. The imaging component of the total ED LOS was compared for patients who met the 4-hour target and patients who did not. RESULTS: Compared to 2011 (before the 4-hour rule), ED presentations increased 4.74% in 2012, 12.7% in 2013, 21.28% in 2014 (p<0.01). Total imaging requests increased 23.05% in 2012, 48.04% in 2013, 60.77% in 2014 (p<0.01). For patients breaching the 4-hour rule, the mean time before radiology request was 2.4-2.8 hours; mean time from imaging request to completion was 1.2 1.3 hours; mean time from imaging completion to discharge from ED was the longest component of ED LOS (4.9-5.9 hours). CONCLUSIONS: There has been a significant increase in imaging requests, with a trend towards more CT and less radiography requests. Imaging requests for patients who breached the 4-hour target were made on average 2.4-2.8 hours after triage and average time after imaging in itself, exceeded 4 hours. Imaging is not likely a causative factor for patients breaching the 4-hour target. PMID- 26997430 TI - Multi-technique imaging of bone metastases: spotlight on PET-CT. AB - There is growing evidence that molecular imaging of bone metastases with positron emission tomography (PET) can improve diagnosis and treatment response assessment over current conventional standard imaging methods, although cost-effectiveness has not been assessed. In most cancer types, 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG)-PET is an accurate method for detecting bone metastases. For example, in breast cancer, combined (18)F-FDG-PET and computed tomography (CT) is more sensitive at detecting bone metastases than (99m)technetium (Tc)-labelled diphosphonate planar bone scintigraphy (BS) and there is increasing evidence to support the use of serial (18)F-FDG-PET for the assessment of osseous response to treatment. Preliminary data suggest improved diagnostic accuracy of (18)F-FDG-PET CT in a number of other malignancies including lung, thyroid, head and neck, gastro-oesophageal cancers, and osteosarcoma. As a bone-specific tracer, there is accumulating evidence to support the use of sodium (18)F-fluoride ((18)F-NaF) PET CT in the diagnosis of skeletal metastases in breast and prostate cancer, although relatively little data are available to support its use for assessment of treatment response. In prostate cancer, (11)C-choline and (18)F-choline PET-CT have better specificities than (18)F-NaF-PET-CT, but equivalent sensitivities in the detection of bone metastases. We review the current literature for staging and response assessment of bone metastases in different cancers. PMID- 26997431 TI - Charge-Convertible Carbon Dots for Imaging-Guided Drug Delivery with Enhanced in Vivo Cancer Therapeutic Efficiency. AB - Carbon dots (CDs) are remarkable nanocarriers due to their promising optical and biocompatible capabilities. However, their practical applicability in cancer therapeutics is limited by their insensitive surface properties to complicated tumor microenvironment in vivo. Herein, a tumor extracellular microenvironment responsive drug nanocarrier based on cisplatin(IV) prodrug-loaded charge convertible CDs (CDs-Pt(IV)@PEG-(PAH/DMMA)) was developed for imaging-guided drug delivery. An anionic polymer with dimethylmaleic acid (PEG-(PAH/DMMA)) on the fabricated CDs-Pt(IV)@PEG-(PAH/DMMA) could undergo intriguing charge conversion to a cationic polymer in mildly acidic tumor extracellular microenvironment (pH ~ 6.8), leading to strong electrostatic repulsion and release of positive CDs Pt(IV). Importantly, positively charged nanocarrier displays high affinity to negatively charged cancer cell membrane, which results in enhanced internalization and effective activation of cisplatin(IV) prodrug in the reductive cytosol. The in vitro experimental results confirmed that this promising charge-convertible nanocarrier possesses better therapeutic efficiency under tumor extracellular microenvironment than normal physiological condition and noncharge-convertible nanocarrier. The in vivo experiments further demonstrated high tumor-inhibition efficacy and low side effects of the charge convertible CDs, proving its capability as a smart drug nanocarrier with enhanced therapeutic effects. The present work provides a strategy to promote potential clinical application of CDs in the cancer treatment. PMID- 26997432 TI - Chaperone protein L-isoaspartate (D-aspartyl) O-methyltransferase as a novel predictor of poor prognosis in lung adenocarcinoma. AB - Endoplasmic reticulum stress and chaperone dysfunction have recently been associated with poor prognoses in various cancers. The newly discovered chaperone protein L-isoaspartyl (D-aspartyl) O-methyltransferase (PIMT) regulates the viability of cancer cells in various cancers, although no clinical information regarding the relationship between lung cancer and PIMT expression has been reported. In this study, we aimed to elucidate the relationship between PIMT expression and the prognosis of lung adenocarcinoma. Paraffin-embedded lung tissues obtained from 208 patients with surgically resected lung adenocarcinoma were subjected to immunohistochemical analyses using primary antibodies against PIMT. Kaplan-Meier curves, log-rank tests, and the Cox proportional hazards model were used to analyze the association between PIMT expression and patient survival. Strong PIMT expression was detected in 106 (50.9%) patients, being particularly observed in patients with advanced stages of lung adenocarcinoma. Strong PIMT expression was associated with that of 78-kDa glucose-regulated protein, a marker of endoplasmic reticulum stress. Patients with strong PIMT expression had a shorter survival time (Kaplan-Meier analysis, P<.001). Multivariate Cox hazard regression analysis demonstrated that strong PIMT expression was an independent predictor of poor prognosis of lung adenocarcinoma, including those with stage I disease (hazard ratios, 6.45 and 6.81, respectively; 95% confidence intervals, 2.46-16.9 and 1.79-25.8, respectively; P<.001 and P=.005, respectively). Collectively, strong PIMT expression was a predictive marker of poor prognosis for surgically resected lung adenocarcinoma, and this finding might help clinicians determine the need for postoperative adjuvant chemotherapy in patients with stage I lung adenocarcinoma. PMID- 26997433 TI - Microvascular injury in persistent gastric ulcers after yttrium-90 microsphere radioembolization for liver malignancies. AB - Yttrium-90 microsphere radioembolization ((90)Y MRE) is a therapy for liver malignancies by permanently implanting (90)Y-containing microspheres into tumors via hepatic artery. The etiology of persistent gastric ulcerations in patients presenting months after treatment remains unclear. Three patients who presented with gastric ulceration 4 to 13 months after (90)Y MRE were examined by esophagogastroduodenoscopy and biopsies. Pathological examinations showed multiple (90)Y microspheres scattered within the lamina propria and submucosa. Most of the microspheres were distributed in a linear fashion, consistent with an intravascular location; however, the vascular lumen and endothelial cells were not present. The microspheres were surrounded by fibrotic tissue infiltrated by chronic inflammatory cells and rare neutrophils. Epithelial granulation without pititis and miniaturized glands with intervening fibrosis were noted, compatible with chronic ischemic changes. These findings suggest that the persistent gastric ulceration is a result of localized ischemic injury in response to (90)Y MRE induced vascular damage. PMID- 26997434 TI - Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance. AB - The glycosyltransferases chondroitin sulfate synthase 1 (CHSY1) and exostoses like 3 (EXTL3) specifically function in biosynthesis of the glycans chondroitin sulfate and heparan sulfate, respectively. Although these glycans play important roles in pathogenesis of various tumors, their significance in soft tissue sarcoma remains unknown. Here, we asked whether CHSY1 or EXTL3 expression correlates with malignant potential of soft tissue sarcomas with myxoid substance. To do so, we examined 40 samples representing specific types, including 12 cases of myxoid liposarcoma, 14 of myxofibrosarcoma, 12 of malignant peripheral nerve sheath tumor, and 2 of low-grade fibromyxoid sarcoma. We performed immunohistochemistry with anti-CHSY1 and anti-EXTL3 antibodies and compared enzyme expression levels with tumor histologic grade as assessed by the Federation Nationale des Centres de Lutte Contre le Cancer classification and with patient 5-year survival rate. CHSY1 and EXTL3 were expressed in 72.5% and 32.5% of all tumors, respectively. Notably, CHSY1 was strongly expressed in myxofibrosarcoma and malignant peripheral nerve sheath tumor compared with other tumors and significantly associated with higher- rather than lower-grade tumors (P < .01). High expression of CHSY1 was also significantly associated with poorer patient outcomes (P = .031) and higher stages assessed by American Joint Committee on Cancer staging system (P = .004). By contrast, EXTL3 expression was not correlated with histologic grade or patient prognosis. We conclude that CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance. PMID- 26997435 TI - Immunohistochemical molecular analysis indicates hepatocellular carcinoma subgroups that reflect tumor aggressiveness. AB - Histopathologic parameters and molecular markers are widely accepted as useful predictors of tumor aggressiveness in hepatocellular carcinoma (HCC). However, few studies have analyzed immunohistochemical profiles comprehensively in one series, a fact that has resulted in fragmentation of information that could be applied in clinical practice. We conducted immunohistochemical expression analysis of biliary/stem cell markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule, and CD133), Wnt/beta-catenin signaling-related molecules (beta-catenin and glutamine synthetase), p53, and cell proliferation markers (Ki-67 and mitosis) in 162 HCCs surgically resected from 142 patients and analyzed the results with respect to clinicopathological features. Immunohistochemical analysis broadly identified 3 groups: the biliary/stem cell marker-positive group, the Wnt/beta-catenin signaling-related marker-positive group, and the biliary/stem cell marker-negative and Wnt/beta-catenin signaling related marker-negative group. p53 was frequently positive in the biliary/stem cell marker-positive group, but it was rarely positive in the Wnt/beta-catenin signaling-related marker-positive group. The biliary/stem cell marker-positive group exhibited poor tumor differentiation, increased frequency of portal vein invasion and/or intrahepatic metastasis, and highly proliferative activity. In contrast, the biliary/stem cell marker-negative and Wnt/beta-catenin signaling related marker-negative group exhibited better tumor differentiation, a decreased frequency of portal vein invasion and/or intrahepatic metastasis, and less proliferative activity. The Wnt/beta-catenin signaling-related marker-positive group showed neither tendency. The biliary/stem cell marker-positive group had the shortest time to recurrence among the 3 groups. Immunohistochemical profiling of HCC reflects tumor aggressiveness and suggests the potential efficacy of immunohistochemistry-based subclassification of HCC. PMID- 26997436 TI - Bronchial involvement in advanced stage lymphangioleiomyomatosis: histopathologic and molecular analyses. AB - Lymphangioleiomyomatosis (LAM), a rare progressive disease that almost exclusively affects women, is characterized by pulmonary cysts and neoplastic proliferation of smooth muscle-like cells (LAM cells). Airflow obstruction is a physiologic consequence that is commonly observed in LAM and has been attributed to narrowing of peripheral airways. However, histopathologic examinations of the entire airway have been precluded by the limited availability of such specimens. Here, we used explanted lung tissues from 30 LAM patients for a thorough histologic analysis with a special emphasis on the bronchi. We found bronchial involvement by LAM cells and lymphatics in all patients examined. Furthermore, a moderate to severe degree of chronic inflammation (73%), goblet cell hyperplasia (97%), squamous cell metaplasia (83%) of the epithelium, and thickening of basal lamina (93%) were identified in the bronchi. Because LAM cells are transformed by the functional loss of the TSC genes leading to a hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, we confirmed the expression of phospho-p70S6K, phospho-S6, phospho-4E-BP1, and vascular endothelial growth factor (VEGF)-D in LAM cells from all of the patients examined. In contrast, no protein expression of hypoxia-inducible factor 1alpha, a downstream molecule indicative of mTORC1 activation and leading to VEGF production, was detected in any patient. Our study indicates that late-stage LAM patients commonly have bronchi involved by the proliferation of both LAM cells and lymphatics and that chronic inflammation complicated their disease. Furthermore, the up-regulation of hypoxia-inducible factor 1alpha, a common event in mTORC1-driven tumor cells, does not occur in LAM cells and plays no role in VEGF-D expression in LAM cells. PMID- 26997437 TI - May Sonic Hedgehog proteins be markers for malignancy in uterine smooth muscle tumors? AB - Several studies have demonstrated that the Sonic Hedgehog signaling pathway (SHH) plays an important role in tumorigenesis and cellular differentiation. We analyzed the protein expression of SHH pathway components and evaluated whether their profile could be useful for the diagnosis, prognosis, or prediction of the risk of malignancy for uterine smooth muscle tumors (USMTs). A total of 176 samples (20 myometrium, 119 variants of leiomyoma, and 37 leiomyosarcoma) were evaluated for the protein expression of the SHH signaling components, HHIP1 (SHH inhibitor), and BMP4 (SHH target) by immunohistochemistry. Western blot analysis was performed to verify the specificity of the antibodies. We grouped leiomyoma samples into conventional leiomyomas and unusual leiomyomas that comprise atypical, cellular, mitotically active leiomyomas and uterine smooth muscle tumors of uncertain malignant potential. Immunohistochemical analysis showed that SMO, SUFU, GLI1, GLI3, and BMP4 expression gradually increased depending on to the histologic tissue type. The protein expression of SMO, SUFU, and GLI1 was increased in unusual leiomyoma and leiomyosarcoma samples compared to normal myometrium. The inhibitor HHIP1 showed higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLI1, and GLI3 was detected in these samples. Strong expression of SHH was associated with poorer overall survival. Our data suggest that the expression of SHH proteins can be useful for evaluating the potential risk of malignancy for USMTs. Moreover, GLI1 and SMO may serve as future therapeutic targets for women with USMTs. PMID- 26997439 TI - MAGE-A expression, immune microenvironment, and prognosis in upper urinary tract carcinoma. AB - The melanoma-associated antigen A (MAGE-A) family comprises cancer-testis antigens that represent promising prognostic biomarkers and immunotherapy targets in several cancer types. The aim of this study was to investigate the significance of MAGE-A expression in upper urinary tract urothelial carcinoma in relation to clinicopathological features, lymphocytic infiltration, and clinical outcome. We immunohistochemically examined the expression of MAGE-A in 171 patients with upper urinary tract urothelial carcinoma. High (>= 50% positive) and low MAGE-A expression levels were observed in 33 (19%) and 49 (29%) cases, respectively. MAGE-A was negative in 89 cases (52%). MAGE-A expression was positively correlated with high histologic grade; concomitant carcinoma in situ; higher Ki-67 proliferation index; and infiltration of CD3-, CD8-, and CD45RO positive T lymphocytes, but not with CD20-positive B lymphocytes. High MAGE-A expression was significantly associated with shorter metastasis-free survival after nephroureterectomy (log-rank P = .019; multivariate hazard ratio, 1.98; 95% confidence interval, 1.00-3.92). MAGE-A expression in metastatic lymph nodes was highly correlated with its expression in primary lesions. MAGE-A expression was retained in chemotherapy-resistant metachronous metastatic lesions of urothelial carcinoma. MAGE-A may be a promising prognostic biomarker and potential immunotherapeutic target for patients with upper urinary tract urothelial carcinoma. PMID- 26997438 TI - Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma. AB - Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P = .0026 and P = .0026) and nonkeratinizing histology (P = .0002 and P = .0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P = .0667) and worse overall survival (P < .0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P < .0001 and P < .0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy. PMID- 26997440 TI - A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification. AB - In contrast to long bone osteosarcoma, mandibular osteosarcoma is highly heterogeneous and morphologically overlaps with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction and sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type 2) overexpression, GNAS (guanine nucleotide binding protein/alpha subunit) mutations, and amplification of MDM2 and/or RASAL1 (RAS protein activator like 1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including 2 with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other 3 contained a coamplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcomas are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement for closer follow-up and more aggressive management. PMID- 26997442 TI - Low incidence of KRAS, BRAF, and PIK3CA mutations in adenocarcinomas of the ampulla of Vater and their prognostic value. AB - Ampullary adenocarcinomas (A-ACs) are rare malignancies with considerable importance because of their high curable resection rate and improved survival rate among periampullary cancers. The RAS-RAF-MAPK pathway is involved in the development of A-ACs and is a potential therapeutic target. However, molecular profiles of A-ACs and their prognostic impact are poorly understood. Peptide nucleic acid-mediated polymerase chain reaction clamping and Mutyper were used to detect KRAS, BRAF, and PIK3CA mutations in 62 paraffinized samples of A-ACs. Of 62 A-ACs, 30.6% had KRAS mutations, but no BRAF mutations and low frequency (1.6%) of PIK3CA mutation were detected. KRAS mutation was correlated with poor tumor differentiation and was a predictor of shorter recurrence-free survival period in overall A-ACs, whereas the prognosis according to the histologic subtypes was not affected by KRAS mutation. Lymph node metastasis was an independent prognostic factor of poor overall survival. Intestinal- and pancreatobiliary-type A-ACs had similar prognosis. Intestinal- and pancreatobiliary-type A-ACs had different prognostic factors; tumor differentiation and lymph node metastasis strongly predicted overall survival and recurrence-free survival in pancreatobiliary-type tumors, respectively, whereas no independent prognostic factors were demonstrated for intestinal-type tumors. Low incidence of KRAS mutations and their strong prognostic value in A-ACs may suggest the potential of survival benefit depending on the epidermal growth factor receptor-targeted therapy. Much lower frequencies of BRAF and PIK3CA mutations may suggest that they do not play a major role in the tumorigenesis of A-ACs. Different therapeutic protocols should be considered for treating pancreatobiliary- and intestinal-type A-ACs. PMID- 26997441 TI - BRAF inhibitor therapy-associated melanocytic lesions lack the BRAF V600E mutation and show increased levels of cyclin D1 expression. AB - Newly appearing or changing melanocytic lesions (MLs) are a recently reported toxicity of BRAF inhibitor (BRAFi) therapy. Morphologically, MLs associated with BRAFi therapy (BRAFi-MLs) may demonstrate alarming features of melanoma with an epithelioid cell phenotype with notable cytologic atypia. We sought to characterize the clinicopathological and molecular features of BRAFi-MLs. A retrospective review over a 4-year period revealed 20 patients in which 44 MLs (including 11 control nevi) were characterized by histopathology, review of clinical medical records, and immunohistochemical (IHC) studies (with anti-BRAF V600E, anti-BAP1, anti-cyclin D1, and anti-p16); the percentage of IHC+ cells was scored. Of the 20 patients, 3 (15%) whose BRAFi-MLs were biopsied had a second primary cutaneous melanoma. Of the 44 BRAFi-MLs tested, 37 (100%) of 37 MLs available for BRAF V600E testing lacked expression in contrast to 1 (9%) of 11 control nevi (lesions not associated with targeted therapy). A significantly higher level of cyclin D1 expression (>50% IHC+ cells) was more commonly seen in BRAFi-MLs (44%) than in control nevi (9%). No difference in p16 expression in melanocytes was seen between the 2 groups. BRAF mutation status distinctly differs between BRAFi-MLs from melanomas and nevi biopsied in patients who do not receive BRAFi therapy. Morphologically, BRAFi-MLs demonstrate a greater degree of atypia than do control nevi. Furthermore, BRAFi-MLs with coexisting cutaneous keratinocyte toxicity developed during fewer days of targeted therapy. Paradoxical activation of the MAPK pathway in BRAF(WT) melanocytes may account for ~15% to 21% of patients developing a second new primary melanoma within a year of starting BRAFi therapy; thus, close clinical surveillance is warranted. PMID- 26997443 TI - CYP24A1 is a potential biomarker for the progression and prognosis of human colorectal cancer. AB - Our study aims to fully evaluate clinicopathological and prognostic values of CYP24A1 in colorectal cancer (CRC) patients. Tissue microarrays of formalin-fixed and paraffin-embedded tumor samples and matched adjacent nontumor colorectal tissues from 99 CRC patients were studied for CYP24A1 protein expression by immunohistochemistry. Messenger RNA expression of CYP24A1 was further evaluated by quantitative real-time polymerase chain reaction in 12 pairs of fresh frozen CRC samples. CYP24A1 expression was significantly higher in CRC tissues compared to corresponding noncancerous tissues. The expression of CYP24A1 protein in CRC was correlated with the depth of tumor invasion (P = .000), lymph node metastasis (P = .030), venous permeation (P = .016), and overall survival (P = .008). A Kaplan-Meier analysis of the CRC patients with high CYP24A1 expression showed significantly reduced overall survival and disease-free survival compared to the patients with low expression (P = 0.026 and .009). A prognostic significance of CYP24A1 was also found in the subgroup of venous permeation condition classification. A multivariate Cox regression analysis showed that CYP24A1 expression was an independent prognostic factor for CRC recurrence (P = .032). In conclusion, CYP24A1 expression is closely associated with CRC progression, and it might be a novel prognostic biomarker for CRC. PMID- 26997444 TI - Dyspoietic changes associated with hepatosplenic T-cell lymphoma are not a manifestation of a myelodysplastic syndrome: analysis of 25 patients. AB - Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell lymphoma commonly associated with cytopenias. The pathogenesis of cytopenias in patients with HSTCL is not well defined, although the presence of dyspoietic hematopoietic cells and the common association with trisomy 8 raise the possibility of an associated myelodysplastic syndrome (MDS). In 25 bone marrow specimens involved by HSTCL, we systematically assessed for morphologic features of dyspoiesis and correlated the findings with peripheral cytopenia(s), cytogenetic findings, and detection of chromosome 8 by fluorescence in situ hybridization. The median patient age was 33 years. One patient had a history of MDS diagnosed 1 year prior to the diagnosis of HSTCL. Thirteen (54%) patients had anemia less than 100 g/L, 10 (53%) of 19 had neutropenia less than 1.8 * 10(9)/L, and 15 (60%) had thrombocytopenia less than 100 * 10(9)/L. Dyspoietic features were identified in 1 to 3 hematopoietic cell lineages in 20 (80%) of 25 patients. Cytogenetic analysis identified trisomy 8 in 7 cases. Patients with trisomy 8 had a lower platelet count, but trisomy 8 was not associated with cytopenias, dyspoietic features, or cytogenetic abnormalities. Combined morphologic and fluorescence in situ hybridization analysis showed that trisomy 8 was restricted to the lymphoma cells, except in the 1 patient with a history of MDS. In conclusion, dyspoietic changes are common in the bone marrow of patients with HSTCL. These changes are not associated with cytopenias or chromosomal abnormalities, suggesting that dyspoiesis in patients with HSTCL is not a manifestation of a MDS. PMID- 26997446 TI - Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis on histopathology. AB - Sprue-like enteropathy associated with the angiotensin II receptor blocker (ARB) olmesartan was first described in 2012, and a number of cases have since been reported. This syndrome is characterized by severe diarrhea and sprue-like histopathologic findings in the intestine, often with increased subepithelial collagen. The incidence of this adverse drug reaction is not entirely clear, although it is thought to be rare. It is also not well established if other ARBs cause such a syndrome, although case reports suggest they can. The histopathologic features of olmesartan-related injury have only been described in a limited number of cases, and there are no guidelines regarding the histopathologic distinction of olmesartan-associated enteropathy from other causes of sprue (eg, celiac disease, tropical sprue). Herein, we review the histopathologic changes and clinical observations described in recent reports of olmesartan-associated sprue-like enteropathy comprising case series and isolated reports, other relevant literature, and our experience at a referral center specializing in small intestinal disorders. We will review recent literature suggesting other ARBs can be associated with a similar phenotype. Lastly, we will discuss the histopathologic differential diagnosis and provide clues to distinguish this entity from other entities which can cause sprue-like histopathology. PMID- 26997445 TI - miR-31 and miR-17-5p levels change during transformation of follicular lymphoma. AB - The 30% of patients whose indolent follicular lymphoma transforms to aggressive diffuse large B-cell lymphoma (DLBCL) have poor survival. Reliable predictors of follicular B-cell lymphoma transformation to DLBCL are lacking, and diagnosis of those that will progress is challenging. MicroRNA, which regulates gene expression, has critical functions in the growth and progression of many cancers and contributes to the pathogenesis of lymphoma. Using 5 paired samples from patients who presented with follicular lymphoma and progressed to DLBCL, we identified specific microRNA differentially expressed between the two. Specifically, miR-17-5p levels were low in follicular lymphoma and increased as the disease transformed. In contrast, miR-31 expression was high in follicular lymphoma and decreased as the lymphoma progressed. These results were confirmed in additional unpaired cases of low-grade follicular lymphoma (n = 13) and high grade follicular lymphoma grade 3 or DLBCL (n = 17). Loss of miR-31 expression in DLBCL was not due to deletion of the locus. Changes in miR-17-5p and miR-31 were not correlated with immunophenotype, genetics, or status of the MYC oncogene. However, increased miR-17-5p expression did significantly correlate with increased expression of p53 protein, which is indicative of mutant TP53. Two pro proliferative genes, E2F2 and PI3KC2A, were identified as direct messenger RNA targets of miR-31, suggesting that these may contribute to follicular lymphoma transformation. Our results indicate that changes in miR-31 and miR-17-5p reflect the transformation of follicular lymphoma to an aggressive large B-cell lymphoma and may, along with their targets, be viable markers for this process. PMID- 26997448 TI - Reporting the greatest linear extent of ductal carcinoma in situ on needle core biopsy. AB - Ductal carcinoma in situ (DCIS) of the breast is staged as pTis regardless of size; however, extent of DCIS correlates with local recurrence rates and likelihood of close or positive margins. As a result, DCIS extent influences patient management and is an important element in the College of American Pathologists tumor summary checklist for excision specimens. There are no recommendations regarding routine reporting of DCIS extent on needle core biopsy material, and to our knowledge, no systematic studies have evaluated the impact of reporting this in biopsy material. Consecutive cases of DCIS performed or reviewed at our institution were identified by pathology report search over a 7 year period. The greatest linear extent of DCIS on core biopsy was compared with the estimated extent in the excision. Of 241 total cases, there were 157 (65%) cases in which the DCIS extent on biopsy was smaller, 13 (5%) cases in which the sizes were equal, and 70 (29%) cases in which the biopsy size was greater, including 30 (12%) with no residual tumor on excision. Mean extent was greater on excision than on core biopsy (16.0 versus 5.7 mm; P < .0001); however, the opposite was seen when only small tumors (<= 10 mm final size) were considered (4.5 versus. 3.6 mm; P = .0161). There was strong linear correlation (r = 0.9761; P < .0001) between the size change (excision size minus biopsy size) and final pathologic size. For accurate tumor summary checklist completion, DCIS extent should be reported for needle biopsy material, particularly in the setting of small tumors. PMID- 26997447 TI - Expression of liver fatty acid binding protein in hepatocellular carcinoma. AB - Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the possibility that LFABP down regulation may be associated with hepatocellular carcinogenesis. Our aim was to evaluate hepatocellular carcinomas arising in various backgrounds and with varying degrees of differentiation for loss of LFABP staining. Twenty total cases of hepatocellular carcinoma were examined. Thirteen cases arose in a background of cirrhosis due to hepatitis C (n = 8) or steatohepatitis (n = 5); 7 cases arose in a noncirrhotic background, with 2 cases arising within HNF1A-inactivated variant HCA and 2 cases arising within inflammatory variant HCA. Complete loss of expression of LFABP was seen in 6 of 20 cases, including 2 cases of hepatocellular carcinoma arising within HNF1A-inactivated variant HCA. Thus, loss of staining for LFABP appears to be common in hepatocellular carcinoma and may be seen in well-differentiated hepatocellular carcinoma. Therefore, LFABP loss should not be interpreted as evidence for hepatocellular adenoma over carcinoma, when other features support a diagnosis of hepatocellular carcinoma. The findings raise consideration for a role of HNF1A inactivation in hepatocellular carcinogenesis, particularly in less differentiated tumors. PMID- 26997449 TI - Frameshift mutation of WISP3 gene and its regional heterogeneity in gastric and colorectal cancers. AB - WISP3 is involved in many cancer-related processes including epithelial mesenchymal transition, cell death, invasion, and metastasis and is considered a tumor suppressor. The aim of our study was to find whether WISP3 gene was mutated and expressionally altered in gastric (GC) and colorectal cancers (CRCs). WISP3 gene possesses a mononucleotide repeat in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 156 CRCs, and found that GCs (8.8%) and CRCs (10.5%) with MSI-H, but not those with microsatellite stable/low MSI, harbored a frameshift mutation. We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the WISP3 mutation exhibited regional ITH in 25% of the CRCs. In immunohistochemistry, loss of WISP3 expression was identified in 24% of GCs and 21% of CRCs. The loss of expression was more common in those with WISP3 mutation than with wild-type WISP3 and those with MSI-H than with microsatellite stable/low MSI. Our data indicate that WISP3 harbored not only frameshift mutation but also mutational ITH and loss of expression, which together might play a role in tumorigenesis of GC and CRC with MSI-H by inhibiting tumor suppressor functions of WISP3. Our data also suggest that mutation analysis in multiregions is needed for a proper evaluation of mutation status in GC and CRC with MSI-H. PMID- 26997450 TI - Aberrant expression of Sonic hedgehog signaling in Peutz-Jeghers syndrome. AB - The SHH signaling pathway is critical for gastrointestinal development and organic patterning, and dysregulation of SHH pathway molecules has been detected in multiple gastrointestinal neoplasms. This study investigated the role of the SHH signaling pathway in PJS. Expression of SHH, PTCH, and GLI1 was examined by real-time PCR and immunohistochemistry in 20 normal tissues and 75 colorectal lesions (25 PJPs, 25 adenomas, and 25 adenocarcinomas). Expression of SHH, PTCH, and GLI1 mRNA was higher in PJPs than in normal tissue (P < .05) and gradually increased along the PJP-adenoma-adenocarcinoma sequence (P < .05). Immunostaining indicated that SHH expression was present in 60% of PJPs, 72% of adenomas, and 84% of carcinomas, whereas 68% of PJPs, 72% of adenomas, and 88% of carcinomas exhibited cytoplasmic expression of PTCH. Moreover, high GLI1 expression was detected in 56% of PJPs, 64% of adenomas, and 80% of carcinomas; and high nuclear expression of GLI1 was observed in 8 adenomas with atypia and 15 carcinomas. Increased SHH, PTCH, and GLI1 protein correlated positively with tumor grade (P = .012, P = .003, and P = .007, respectively), tumor depth (P = .024, P = .007, and P = .01), and lymph node metastasis (P = .05, P = .015, and P = .005). This study identified aberrant expression of SHH pathway molecules in PJS, and the findings may supply a novel mechanism for the development of PJ polyps. PMID- 26997451 TI - MAP3K3 overexpression is associated with poor survival in ovarian carcinoma. AB - Mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is ubiquitously expressed in numerous tissues and is activated by various extracellular stimuli to regulate processes, such as cell proliferation and differentiation. Recent studies have identified potentially pathologic conditions of MAP3K3 as an oncogene that promotes tumor progression and metastasis in a number of malignancies. However, the clinical significance of MAP3K3 expression in ovarian carcinoma (OC) remains unclear. In this study, the correlation between MAP3K3 expression and OC prognosis was assessed by immunohistochemistry. MAP3K3 overexpression was observed in 59.1% (55/93) of OCs and was significantly associated with histological type and grade, chemotherapy response, and challenge model (P < .05, respectively). MAP3K3 overexpression was also used as an independent prognostic marker for decreased disease-free survival and overall survival. In OC cell lines, MAP3K3 expression was evaluated by Western blot analysis, quantitative real-time polymerase chain reaction, and immunofluorescence. High MAP3K3 expression is significantly detected in SKOV3, C13*, and A2780 cells. All these findings suggested that MAP3K3 overexpression is an independent poor prognostic indicator of OC and can be a clinically effective biomarker of OC. PMID- 26997452 TI - p16 expression predicts neoadjuvant tumor necrosis in osteosarcomas: reappraisal with a larger series using whole sections. AB - The presence of greater than or equal to 90% necrosis after neoadjuvant chemotherapy is a favorable prognostic factor in osteosarcomas. A recent study using tissue microarrays of 40 conventional osteosarcomas showed that p16 expression independently predicted the necrotic response to neoadjuvant chemotherapy. In this study, we investigated this finding using whole sections in a larger group of osteosarcomas. Cases of 83 patients who had pretreatment biopsies and received neoadjuvant chemotherapy and surgical resection were collected from 3 reference hospital archives. Age, sex, tumor size, tumor subtype, location, and percentage of tumor necrosis were recorded; 4-MUm sections from pretreatment biopsies were stained for p16. More than 30% strong nuclear staining was regarded as positive. The median age was 17 years (5-68 years), and male/female ratio was 2.3. The mean tumor diameter was 9.9 cm (2-30 cm). Tumors were most commonly of the osteoblastic type (60%) and located at the femur (47%). p16 positivity was seen in 66% of the patients. The median pathologic necrosis was 65%, and 39% of the patients responded favorably (>=%90 necrosis) to neoadjuvant therapy. In univariate analysis, p16 expression significantly correlated with greater than or equal to 90% response (P = .022). On multivariate analysis, p16 expression (odds ratio [OR], 7.71; P = .008), female sex (OR, 8.62; P = .006), and smaller tumor size (OR, 0.86; P = .023) were independent predictors of favorable response to neoadjuvant chemotherapy. We confirmed the finding that p16 expression predicts postchemotherapy necrotic response in conventional osteosarcomas. PMID- 26997453 TI - Giant cell interstitial pneumonia in patients without hard metal exposure: analysis of 3 cases and review of the literature. AB - Giant cell interstitial pneumonia is a rare lung disease and is considered pathognomonic for hard metal lung disease, although some cases with no apparent hard metal (tungsten carbide cobalt) exposure have been reported. We aimed to explore the association between giant cell interstitial pneumonia and hard metal exposure. Surgical pathology files from 2001 to 2004 were searched for explanted lungs with the histopathologic diagnosis of giant cell interstitial pneumonia, and we reviewed the associated clinical histories. Mass spectrometry, energy dispersive x-ray analysis, and human leukocyte antigen typing data were evaluated. Of the 455 lung transplants, 3 met the histologic criteria for giant cell interstitial pneumonia. Patient 1 was a 36-year-old firefighter, patient 2 was a 58-year-old welder, and patient 3 was a 45-year-old environmental inspector. None reported exposure to hard metal or cobalt dust. Patients 1 and 2 received double lung transplants; patient 3 received a left single-lung transplant. Histologically, giant cell interstitial pneumonia presented as chronic interstitial pneumonia with fibrosis, alveolar macrophage accumulation, and multinucleated giant cells of both alveolar macrophage and type 2 cell origin. Energy-dispersive x-ray analysis revealed no cobalt or tungsten particles in samples from the explanted lungs. None of the samples had detectable tungsten levels, and only patient 2 had elevated cobalt levels. The lack of appropriate inhalation history and negative analytical findings in the tissue from 2 of the 3 patients suggests that giant cell interstitial pneumonia is not limited to individuals with hard metal exposure, and other environmental factors may elicit the same histologic reaction. PMID- 26997454 TI - Early signet ring cell carcinoma arising from colonic adenoma: the molecular profiling supports the adenoma-carcinoma sequence. AB - Among colorectal cancers, the prevalence of signet ring cell carcinoma (SRCC) is lower than 1%; to date, only 6 cases of early SRCCs arising in colonic adenoma have been reported. In spite of the well-established understanding of the phenotypic and genetic changes occurring in conventional colonic carcinogenesis, the molecular landscape of colon SRCC is still far to be elucidated. We describe the histologic and immunohistochemical phenotype and the molecular profile of a case of intramucosal SRCC developed within a 4.5-cm large sigmoid adenoma. The DNA sequencing of the 2 microdissected neoplastic components (adenomatous and SRCC) showed the same G12V KRAS mutation. Interestingly, although the adenomatous epithelium showed unequivocal p53 overexpression, no signet ring cancer cells featured p53 nuclear immunostain. This molecular pattern supports the unique histogenesis of the 2 coexisting neoplastic oncotypes, also suggesting that the signet ring cell component is derived from the molecular de-differentiation (p53 loss) of the preexisting adenomatous lesion. PMID- 26997455 TI - Clinicopathological analysis of allogeneic hematopoietic stem cell transplantation-related membranous glomerulonephritis. AB - Allogeneic hematopoietic stem cell transplantation (HSCT)-related membranous glomerulonephritis (MGN) is poorly understood. A total of 830 patients who underwent HSCT at Toranomon Hospital from 2000 to 2012 were evaluated retrospectively, including 621 patients receiving umbilical cord blood transplantation (UCBT) and 208 patients receiving unrelated bone marrow transplantation. MGN was diagnosed in 5 patients after UCBT (versus none after bone marrow transplantation) and occurred concomitantly with chronic graft-versus host disease after cessation of immunosuppression. Light microscopy did not show any definite spikes or bubbling of the glomerular basement membrane (GBM) in all 5 patients. In 1 patient (case 5), endocapillary proliferative lesions with fibrin-like deposits were noted in addition to MGN findings. Immunofluorescence demonstrated granular deposits of immunoglobulin G (IgG; IgG1 and IgG4) along the GBM with negativity for C3, C4, and C1q in 4 patients (cases 1-4), whereas case 5 showed positivity for IgG (IgG1, IgG2, IgG3, and IgG4) as well as for C3, C4, and C1q. Electron microscopy revealed electron-dense deposits in the subepithelial space of the GBM in cases 1-4. In case 5, electron-dense deposits were present in the mesangium and the subendothelial space of the GBM, as well as in the subepithelial space. After treatment with immunosuppressants (prednisolone and/or cyclosporin) or angiotensin-converting enzyme inhibitors, complete remission with disappearance of proteinuria was achieved 12.2 months in all 5 patients, but nephrotic-range proteinuria relapsed in 2 patients during follow-up. Serum anti PLA2R autoantibody was negative in 3 patients. HSCT-related MGN only occurred after UCBT. We believe that there were 2 morphologic patterns: early MGN and membranoproliferative pattern glomerulonephritis. PMID- 26997456 TI - Adipose derived pericytes rescue fractures from a failure of healing--non-union. AB - Atrophic non-union is attributed to biological failure of the fracture repair process. It occurs in up to 10% of fractures, results in significant morbidity to patients, and treatment often requires complex reconstructive procedures. We tested the ability of human bone derived marrow mesenchymal stem cells (MSC), and human adipose derived pericytes (the native ancestor of the MSC) delivered percutaneously to the fracture gap to prevent the formation of atrophic non-union in a rat model. At eight weeks, 80% of animals in the cell treatment groups showed evidence of bone healing compared to only 14% of those in the control group. Radiographic parameters showed significant improvement over the eight-week period in the cell treatment groups, and histology confirmed bone bridges at the fracture gap in the both treatment groups. The quality of bone produced and its biomechanical properties were significantly enhanced in both treatment groups. The results from this study demonstrate that MSC and pericytes have significant bone regeneration potential in an atrophic non-union model. These cells may have a role in the prevention of atrophic non-union and could enable a paradigm shift in the treatment of fractures at high risk of failing to heal and developing non union. PMID- 26997457 TI - Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells. AB - Salinomycin is a promising anti-cancer agent which selectively targets cancer stem cells. To improve its potency and selectivity, an analog library of salinomycin was generated by site-specific modification and CuAAc derivatization. Through a cytotoxicity analysis of the library, a fluorinated analog with high potency, selectivity, and (19)F MRI sensitivity was discovered as a novel theranostic agent. PMID- 26997459 TI - Redefining cancer and cure. PMID- 26997458 TI - Efficacy and safety of ursodeoxycholic acid composite on fatigued patients with elevated liver function and/or fatty liver: a multi-centre, randomised, double blinded, placebo-controlled trial. AB - AIM: The aim of this study was to assess the effects of ursodeoxycholic acid composite (URSA-S) on fatigue in patients with elevated liver function tests and/or fatty liver disease. METHODS: In this multi-centre randomised double blinded placebo-controlled trial, 168 adults who were diagnosed with fatigue based on our criteria and had elevated liver function tests (but not > 5 times the normal level) and/or fatty liver on ultrasonography, were randomised to either the placebo or URSA-S administration group. The rate of improvement of checklist individual strength (CIS) using a cut-off of 76 points at the end of the study (8 weeks), the change in fatigue scale [CIS score and visual analogue scale (VAS)] were evaluated. The adverse effects of URSA-S were also recorded. RESULTS: The rate of CIS improvement at the end-point was 79.76% and 45.68% in the therapy and placebo groups, respectively (p < 0.05). The fatigue recovery rate of the CIS score and VAS were higher in the therapy (-25.44 +/- 18.57, 27.84 +/- 2.70) than in the placebo group (-16.59 +/- 17.29, -19.46 +/- 2.81) (p < 0.05). The difference in fatigue recovery rate between the therapy and placebo groups was significant after 8 weeks. When analysed separately in patients with abnormal liver function tests and fatty liver disease, the fatigue recovery rate of the CIS score and VAS at 8 weeks was higher in the therapy than in the placebo group (p < 0.05). The frequency of adverse events in the therapy group was not significantly higher than that in the placebo group. CONCLUSION: URSA-S is effective for alleviating fatigue in patients with liver dysfunction and/or fatty liver. The adverse effects of URSA-S are not significant. This study is registered at https://clinicaltrials.gov/ct2/show/NCT02415777. PMID- 26997460 TI - Health policy: Strategies to optimize expedited investigational new drug safety reports. PMID- 26997461 TI - [Benign struma ovarii: Report of 7 cases and review of the literature]. AB - OBJECTIVE: Struma ovarii is a monodermal teratoma composed of thyroid tissue, representing 0.85 to 1.3% of ovarian tumors. The objective of the present study is to report a continuous series of struma ovarii, with a comprehensive analysis of the literature. METHODS: A retrospective study in the gynecological surgery department of Hopital Femme-Mere-Enfant (Hospices Civils de Lyon, Lyon, France) assessed a continuous series of struma ovarii from the Lyon East Pathology Center database. Clinical and biological, imaging and pathological aspects were analyzed and the various forms of treatment described. RESULTS: We identified 7 patients with struma ovarii from March 2008 to April 2015. Mean patient age was 49.7 years (28-70years). Three patients had a history of thyroid disease. CA-125 was elevated (51IU/mL) in only 1 patient. MRI and ultrasound imaging did not enable diagnosis of struma ovarii, which depended on pathologic examination. Conservative surgery for cystectomy or oophorectomy was performed for patients wishing to become pregnant (71%); nonconservative hysterectomy was performed in postmenopausal women (29%). CONCLUSIONS: Struma ovarii is a rare, often asymptomatic condition in which diagnosis is difficult. Few series are described in the literature. Here we propose a management model for struma ovarii. Revision surgery and adjuvant therapy is indicated in case of malignant struma ovarii. PMID- 26997462 TI - [The practice of episiotomy in France 10 years after the recommendations of CNGOF: What inventory?]. AB - Since its creation, the practice of episiotomy has evolved, being influenced by several factors. Various stances on its use were stated, until the eventual reduction of this practice, as suggested by numerous practical guides. In 2005, the National College of Obstetricians and Gynecologists in France published its French Guidelines for Clinical practice in this area. Today, it seems appropriate to focus on the evolution of the use of episiotomy, ten years after the publication of these recommendations. The authors propose a literature review, browsing through all the available epidemiological data in France related to episiotomy, recording all national statistics and some local trends, as there are regional specificities. This review allows to follow the overall evolution of the practice of episiotomy in France between 1981 and 2014, and to identify territorial disparities. Finally, in the specific context of the practice of episiotomy in French gynecological and obstetrics field, the authors conclude it by considering the possible evolution of this surgical practice, as well as, the Clinical Practice Recommendations related to it. PMID- 26997463 TI - [Sentinel node detection using optonuclear probe (gamma and fluorescence) after green indocyanine and radio-isotope injections]. AB - OBJECTIVE: Assess the biopsy's feasibility of the sentinel lymph node biopsy (SLNB) using optonuclear probe after of indocyanine green (ICG) and radio-isotope (RI) injections. METHODS: Twenty-one patients with a localized breast cancer and unsuspicious axillary nodes underwent a SLNB after both injections of ICG and radio-isotope. RESULTS: One or more SLN were identified on the 21 patients (identification rate of 100%). The median number SLN was 2 (1-3). Twenty SLN were both radio-actives and fluorescents (54.1%), 11 fluorescent only (29.7%) and 6 were only radio-actives (16.2%). Seven patients had a metastatic SLN (8 SLN overall). Among them, only one had a micrometastasic SLN, 5 others had a macrometastatic SLN and one patient had two macrometastatic SLNs. Among the 8 metastatic SLN, 5 were both fluorescent and radioactive, 2 were only fluorescent and 1 was only radioactive. CONCLUSION: Detection SLN using optonuclear probe after indocyanine green and radio-isotope injections is effective and could be, after validation by randomized trial, a reliable alternative to the blue dye injection for teams who consider that combined detection as the reference. PMID- 26997465 TI - Editorial: Cytokines in inflammation, aging, cancer and obesity. PMID- 26997464 TI - [Assisted reproductive techniques in single women: Which proposals for which demands?]. AB - The French bio-ethic law concerning ART is more restricted than in other countries. Techniques can only be applied in heterosexual couples presenting a documented infertility. Nevertheless, concerns about fertility planning are numerous in young women, leading to a growing demand of reproductive medicine consultations. Two situations can be distinguished: firstly, single patients wishing sperm donation and, secondly, single patients who wish to preserve their fertility for future parenting project. This latter situation can be discussed in the French legislative context while the other will require soliciting the neighboring European teams. PMID- 26997466 TI - [1+1+1] Cyclotrimerization for the Synthesis of Cyclopropanes. AB - The synthesis of small rings by functionalization of C(sp(3) )-H bonds remains a great challenge. We report for the first time a copper-catalyzed [1+1+1] cyclotrimerization of acetophenone derivatives under mild reaction conditions. The reaction has a broad scope for the stereoselective synthesis of cyclopropanes by trimerization of acetophenone. The developed transformation is based on an extraordinary copper-catalyzed cascade process that allows saturated carbocycles to be obtained for the first time by cyclotrimerization through functionalization of C(sp(3) )-H bonds. The cascade of sixfold C(sp(3) )-H bond functionalization allows the synthesis of cyclopropanes in a highly stereoselective approach. PMID- 26997467 TI - Dramatic change in skin color after bilateral adrenalectomy in Cushing's disease. PMID- 26997468 TI - Low vitamin D3 and high anti-Mullerian hormone serum levels in the polycystic ovary syndrome (PCOS): Is there a link? AB - OBJECTIVES: Low vitamin D serum level has been reported in women with polycystic ovary syndrome (PCOS) compared to controls. A few in vitro studies showed that the bioactive form of vitamin D is able to modulate the expression of the anti Mullerian hormone (AMH) gene. However, in vivo studies failed to demonstrate clearly whether low vitamin D3 serum level is involved in the AMH excess of PCOS. This prospective study evaluates serum vitamin D3 and AMH levels in women with PCOS and in controls, before and after vitamin D supplementation. MATERIALS AND METHODS: Among vitamin D deficient patients, 23 patients with PCOS were compared to 27 women with normal ovarian reserve (NOR). The vitamin D deficient patients received a vitamin D supplementation according to the depth of their insufficiency. For the 23 patients with PCOS and the 27 controls, serum AMH assay and serum calciotropic hormone assays [25-hydroxyvitamin D (25[OH]D), 1,25 dihydroxyvitamin D (1,25[OH]2D) and parathyroid hormone (PTH)] were performed before and after supplementation. RESULTS: Serum 25(OH)D levels before treatment were statistically lower in PCOS women than in NOR patients (P<0.05), even after adjustment for BMI, age and AMH level, but not after adjustment for waist circumference measurement. No difference in the serum AMH levels before and after treatment was observed neither in PCOS patients nor in NOR patients. In both groups, 25(OH)D serum levels were not related to serum AMH levels, serum 1,25(OH)2D and serum PTH levels, before and after treatment. CONCLUSION: We found no evidence that serum calciotropic hormones are linked to circulating AMH levels, particularly in PCOS. PMID- 26997470 TI - Homozygous familial hypercholesterolemia: phenotype rules! PMID- 26997469 TI - Beware of manipulations on the genome: epigenetic destabilization through (foreign) DNA insertions. PMID- 26997473 TI - Flux 2 Editorial. PMID- 26997472 TI - beta-1,3-Glucan reverses aflatoxin B1-mediated suppression of immune responses in mice. AB - Aflatoxin B1 (AFB1) is immunotoxic to animals and is a suspected immunosuppressant in humans. beta-1,3-Glucan (BG) consists of glucose polymers and has a variety of stimulatory effects on the immune system. In this study, we investigated the role of BG on the expression of phenotypic markers and cytokine secretion in mice exposed to AFB1. We treated animals with BG (150mg/kg, p.o., once daily) for 7days beginning at the onset of AFB1 exposure. Exposure of animals to AFB1 alone (1250MUg/kg, p.o, once daily) for 7days resulted in a decrease in the percentages of lymphocyte subsets (CD4(+), GITR(+), CD8(+), TCR beta(+), CD3(+), Foxp3(+), CD4(+)Foxp3(+), and CD127(+)) as compared to an normal control (NC). However, both BG alone and BG given in conjunction with exposure to AFB1 significantly increased the percentages of these lymphocyte subsets in blood. We also observed that mice exposed to AFB1 showed reduced IL-2, TNF-alpha, IL-17, and IFN-gamma production in the spleen and serum. In contrast, oral administration of BG alone and in conjunction with AFB1 exposure augmented the levels of these cytokines. Moreover, this finding was confirmed through RT-PCR and western blot analysis of mRNA and protein expression in the spleen. Altogether, it can be concluded from these studies that BG enhances the responses of lymphocyte subsets, including cytokine production, even when given following exposure to AFB1 immunotoxin. These data demonstrate that BG carries out its immunomodulating activity by regulating cytokine production. Our findings also provide a direction for development of specific immunomodulating therapy. PMID- 26997471 TI - Impact of restrictive versus obstructive pulmonary function patterns on mortality in patients undergoing transcatheter aortic valve implantation. AB - BACKGROUND: Pulmonary function tests to estimate force vital capacity (FVC) and forced expiratory volume in the first second (FEV1) have increasingly been used in patients evaluated for transcatheter aortic valve implantation (TAVI). The impact of obstructive versus restrictive lung disease on mortality remains unclear. The authors sought to identify differences in survival in patients with 2 distinct pulmonary function patterns (obstruction vs. restriction). METHODS: The authors retrospectively analyzed all patients with abnormal FEV1 (lower than 80% of predicted) detected on the pulmonary function tests prior to TAVI from May 2011 to November 2014. Patients were divided into a group with obstructive pattern (FEV1/FVC<70% of predicted) and a group with restrictive pattern (FEV1/FVC>70% of predicted). Cox proportional hazards regression was used to explore the impact of FEV1 on mortality. RESULTS: A total of 94 patients were included in this analysis. Forty-one percent (n=38) had obstructive pattern, and 59% (n=56) had restrictive pattern. FEV1 values were similar between both groups (43+/-19 vs. 42+/-26, p=0.89). Both groups had similar rates of in-hospital, 30 day, and 1-year mortality. FEV1 was not a correlate for 1-year mortality. Patients with pulmonary obstructive and restrictive patters had similar rates of mortality. Moreover, FEV1 value is not a correlate for 1-year mortality. CONCLUSION: In the current era, the pattern on pulmonary function tests and FEV1 values should not influence the decision on whom to offer a transcatheter option for their severe valvular disease. PMID- 26997474 TI - Rapid bacterial antibiotic susceptibility test based on simple surface-enhanced Raman spectroscopic biomarkers. AB - Rapid bacterial antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) measurement are important to help reduce the widespread misuse of antibiotics and alleviate the growing drug-resistance problem. We discovered that, when a susceptible strain of Staphylococcus aureus or Escherichia coli is exposed to an antibiotic, the intensity of specific biomarkers in its surface-enhanced Raman scattering (SERS) spectra drops evidently in two hours. The discovery has been exploited for rapid AST and MIC determination of methicillin-susceptible S. aureus and wild-type E. coli as well as clinical isolates. The results obtained by this SERS-AST method were consistent with that by the standard incubation-based method, indicating its high potential to supplement or replace existing time-consuming methods and help mitigate the challenge of drug resistance in clinical microbiology. PMID- 26997475 TI - Early fetal reduction of dichorionic triplets to dichorionic twin or singleton pregnancies: a retrospective study. AB - A retrospective study conducted in an academic reproductive medicine centre evaluated the feasibility and safety of early fetal reduction in dichorionic triplets to dichorionic twin or singleton pregnancies. Thirty-three dichorionic triplets that underwent early transvaginal fetal reduction mechanically between 2002 and 2013 were included, of which 21 patients underwent fetal reduction to dichorionic twins (Group A) and 12 patients underwent fetal reduction to a singleton pregnancy (Group B). A further 84 patients with trichorionic triplets reduced to twins were included as the control group (Group C). The main outcome measures were live birth and preterm labour rates. Both early and late spontaneous abortion rates, were similar in group A compared with groups B and C. Gestational age at delivery was significantly lower in group C versus group A (P = 0.02). The preterm labour rate in group A, which was comparable with that in group C, was greater than in group B, but not significantly. Neonatal birth weight, low birth weight rate and neonatal body height were similar among groups. Small for gestational age rates were comparable. Live birth rates were similar among the groups. Early transvaginal fetal reduction for dichorionic triplets to dichorionic twins may be feasible and safe. PMID- 26997476 TI - Assisted reproductive techniques in Latin America: the Latin American Registry, 2013. AB - Multinational data on assisted reproduction techniques undertaken in 2013 were collected from 158 institutions in 15 Latin American countries. Individualized cycle-based data included 57,456 initiated cycles. Treatments included autologous IVF and intracytoplasmic sperm injection (ICSI), frozen embryo transfers, oocyte donations. In autologous reproduction, 29.22% of women were younger than 35 years, 40.1% were 35-39 years and 30.6% were 40 years or older. Overall delivery rate per oocyte retrieval was 20.6% for ICSI and 25.4% for IVF. Multiple births included 20.7% for twins and 1.1% for triplets and over. In oocyte donations, twins reached 30% and triplets 1.4%. In singletons, pre-term births were 7.5%: 36.58% in twins and 65.52% in triplets. The relative risk for prematurity was 4.9 (95% CI 4.5 to 5.3) in twins and 8.7 (95% CI 7.6 to 10.0) in triplets and above. Perinatal mortality was 29.4 per 1000 in singletons, 39.9 per 1000 in twins and 71.6 per 1000 in high order multiples. Elective single embryo transfer represented only 2% of cycles, with delivery rate of 39.1% in women aged 34 years or less. Given the effect of multiple births and prematurity, it is mandatory to reduce the number of embryos transferred in the region. PMID- 26997477 TI - Outcome after hydrogen sulphide intoxication. AB - AIM: Hydrogen sulphide (H2S) intoxication in man is frequently associated with a fatal outcome. In small animal models hydrogen sulphide has demonstrated profound protection against hypoxia. No reports that focus on a potential protective effect in humans have been published. METHODS: The frequency and outcome of a large cohort of hydrogen sulphide intoxications is described. RESULTS: From 1980 until 2013, 35 accidents totalling 56 victims occurred of whom at least 24 (43%) survived. Of the 8 patients with documented cardiopulmonary resuscitation on the scene, 6 (75%) survived. In some of these cases with good outcome the exposure time to very high hydrogen sulphide levels before extraction and resuscitation was more than 45min. CONCLUSION: Manure related hydrogen sulphide intoxication is associated with a high mortality, although in some cases, recovery appears to be far more favourable than the initial presentation would suggest. Possibly protection from hypoxic injury due to induction of a suspended animation-like state by hydrogen sulphide may be responsible. PMID- 26997478 TI - Rebuttal from Scott A. Summers and Bret H. Goodpaster. PMID- 26997479 TI - Validated Stability-Indicating RP-HPLC Method for Simultaneous Determination of Clorsulon and Ivermectin Employing Plackett-Burman Experimental Design for Robustness Testing. AB - A sensitive and highly selective stability-indicating gradient HPLC method was developed and validated for simultaneous determination of clorsulon (CLO) and ivermectin (IVM) in the presence of their degradation products. The drugs were subjected to different stress conditions, including acid and alkaline hydrolysis, oxidative, thermal, and photolytic forced degradation. The robustness of the proposed method was assessed using the Plackett-Burman experimental design, the factors affecting system performance were defined, and nonsignificant intervals for the significant factors were determined. The separation was carried out on a ZORBAX SB phenyl analytical column (250 * 4.6 mm id, 5 MUm particle size), with gradient elution utilizing 10 mM sodium dihydrogen phosphate and acetonitrile as mobile phase. UV detection was performed for CLO and IVM at 254 nm over a concentration range of 4-140 and 5-50 MUg/mL, respectively, with mean percentage recoveries of 99.90 +/- 1.30 and 98.59 +/- 1.16%, respectively. The proposed method was successfully applied to a pharmaceutical dosage form containing the investigated drugs. The results were statistically compared with the official HPLC methods, and no significant differences were found. PMID- 26997480 TI - Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma. AB - PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2. Innately resistant tumors display a transcriptional signature (referred to as the IPRES, or innate anti-PD-1 resistance), indicating concurrent up-expression of genes involved in the regulation of mesenchymal transition, cell adhesion, extracellular matrix remodeling, angiogenesis, and wound healing. Notably, mitogen-activated protein kinase (MAPK)-targeted therapy (MAPK inhibitor) induces similar signatures in melanoma, suggesting that a non-genomic form of MAPK inhibitor resistance mediates cross-resistance to anti-PD-1 therapy. Validation of the IPRES in other independent tumor cohorts defines a transcriptomic subset across distinct types of advanced cancer. These findings suggest that attenuating the biological processes that underlie IPRES may improve anti-PD-1 response in melanoma and other cancer types. PMID- 26997482 TI - Programmable RNA Tracking in Live Cells with CRISPR/Cas9. AB - RNA-programmed genome editing using CRISPR/Cas9 from Streptococcus pyogenes has enabled rapid and accessible alteration of specific genomic loci in many organisms. A flexible means to target RNA would allow alteration and imaging of endogenous RNA transcripts analogous to CRISPR/Cas-based genomic tools, but most RNA targeting methods rely on incorporation of exogenous tags. Here, we demonstrate that nuclease-inactive S. pyogenes CRISPR/Cas9 can bind RNA in a nucleic-acid-programmed manner and allow endogenous RNA tracking in living cells. We show that nuclear-localized RNA-targeting Cas9 (RCas9) is exported to the cytoplasm only in the presence of sgRNAs targeting mRNA and observe accumulation of ACTB, CCNA2, and TFRC mRNAs in RNA granules that correlate with fluorescence in situ hybridization. We also demonstrate time-resolved measurements of ACTB mRNA trafficking to stress granules. Our results establish RCas9 as a means to track RNA in living cells in a programmable manner without genetically encoded tags. PMID- 26997481 TI - Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake. AB - Homeostatic mechanisms stabilize neural circuit function by keeping firing rates within a set-point range, but whether this process is gated by brain state is unknown. Here, we monitored firing rate homeostasis in individual visual cortical neurons in freely behaving rats as they cycled between sleep and wake states. When neuronal firing rates were perturbed by visual deprivation, they gradually returned to a precise, cell-autonomous set point during periods of active wake, with lengthening of the wake period enhancing firing rate rebound. Unexpectedly, this resetting of neuronal firing was suppressed during sleep. This raises the possibility that memory consolidation or other sleep-dependent processes are vulnerable to interference from homeostatic plasticity mechanisms. PAPERCLIP. PMID- 26997483 TI - The Effect of Sustained Inflammation on Hepatic Mevalonate Pathway Results in Hyperglycemia. AB - Control of plasma glucose level is essential to organismal survival. Sustained inflammation has been implicated in control of glucose homeostasis in cases of infection, obesity, and type 2 diabetes; however, the precise role of inflammation in these complex disease states remains poorly understood. Here, we find that sustained inflammation results in elevated plasma glucose due to increased hepatic glucose production. We find that sustained inflammation suppresses CYP7A1, leading to accumulation of intermediate metabolites at the branch point of the mevalonate pathway. This results in prenylation of RHOC, which is concomitantly induced by inflammatory cytokines. Subsequent activation of RHO-associated protein kinase results in elevated plasma glucose. These findings uncover an unexpected mechanism by which sustained inflammation alters glucose homeostasis. PMID- 26997484 TI - Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating. AB - Mutations in the Kv3.3 potassium channel (KCNC3) cause cerebellar neurodegeneration and impair auditory processing. The cytoplasmic C terminus of Kv3.3 contains a proline-rich domain conserved in proteins that activate actin nucleation through Arp2/3. We found that Kv3.3 recruits Arp2/3 to the plasma membrane, resulting in formation of a relatively stable cortical actin filament network resistant to cytochalasin D that inhibits fast barbed end actin assembly. These Kv3.3-associated actin structures are required to prevent very rapid N-type channel inactivation during short depolarizations of the plasma membrane. The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3. A human Kv3.3 mutation within a conserved proline-rich domain produces channels that bind Hax-1 but are impaired in recruiting Arp2/3 to the plasma membrane, resulting in growth cones with deficient actin veils in stem cell-derived neurons. PMID- 26997486 TI - In vivo reflectance confocal microscopy characterization of silver deposits in localized cutaneous argyria. AB - Localized cutaneous argyria is a rare condition secondary to skin deposition of silver following exposure to substances containing this metal. The clinical appearance and dermoscopy findings require deep melanocytic lesions and particularly melanoma metastasis to be ruled out. Silver deposits are usually confirmed by scanning electron microscopy and/or energy-dispersive X-ray spectroscopy. Herein we describe the in vivo reflectance confocal microscopy (RCM) features observed in one case of localized cutaneous argyria. These features include the presence of a hyperrefractile network in the papillary dermis and a periadnexal dotted bright pattern. In vivo RCM might be a useful tool for an early diagnosis of this uncommon entity. PMID- 26997488 TI - Stability and self-passivation of copper vanadate photoanodes under chemical, electrochemical, and photoelectrochemical operation. AB - Deployment of solar fuels technology requires photoanodes with long term stability, which can be accomplished using light absorbers that self-passivate under operational conditions. Several copper vanadates have been recently reported as promising photoanode materials, and their stability and self passivation is demonstrated through a combination of Pourbaix calculations and combinatorial experimentation. PMID- 26997485 TI - Root Endophyte Colletotrichum tofieldiae Confers Plant Fitness Benefits that Are Phosphate Status Dependent. AB - A staggering diversity of endophytic fungi associate with healthy plants in nature, but it is usually unclear whether these represent stochastic encounters or provide host fitness benefits. Although most characterized species of the fungal genus Colletotrichum are destructive pathogens, we show here that C. tofieldiae (Ct) is an endemic endophyte in natural Arabidopsis thaliana populations in central Spain. Colonization by Ct initiates in roots but can also spread systemically into shoots. Ct transfers the macronutrient phosphorus to shoots, promotes plant growth, and increases fertility only under phosphorus deficient conditions, a nutrient status that might have facilitated the transition from pathogenic to beneficial lifestyles. The host's phosphate starvation response (PSR) system controls Ct root colonization and is needed for plant growth promotion (PGP). PGP also requires PEN2-dependent indole glucosinolate metabolism, a component of innate immune responses, indicating a functional link between innate immunity and the PSR system during beneficial interactions with Ct. PMID- 26997487 TI - The perceived effects of electronic cigarettes on health by adult users: A state of the science systematic literature review. AB - BACKGROUND AND PURPOSE: There is a lack of research on perceived health effects of electronic cigarettes by adult users. Because more people are choosing electronic cigarettes (e-cigarettes) in addition to, or instead of traditional cigarettes, it is important for the nurse practitioner (NP) to understand why. METHODS: A comprehensive literature search was conducted using four scholarly databases. The search strategy utilized remained consistent. Qualitative, quantitative, observational studies and meta-analyses were considered for review. Of the 52 articles preliminarily retrieved, 9 met inclusion criteria and were analyzed. CONCLUSIONS: The majority of e-cigarette users perceive they are less harmful to health than traditional cigarettes. One reason for use is smoking cessation. Current guidelines recommend against promoting e-cigarette use. More research is needed on the long-term health effects of e-cigarettes as well as regulatory statements to guide future healthcare practice. IMPLICATIONS FOR PRACTICE: As prevalence of e-cigarette use increases, it is important for NPs to understand the perceived effects on health by adults who use them and, specifically, how these perceptions motivate use. Armed with this information, the NP can communicate with patients about e-cigarettes, confidently recommend against their use, and begin discussions about reliable smoking cessation tools and resources that will help patients achieve their goals. PMID- 26997489 TI - The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica). AB - Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO S-genes of phylogenetic clade V up-regulated upon PM inoculation, such as MdMLO11 and 19 (clade V) and MdMLO18 (clade VII). We report the knock-down through RNA interference of MdMLO11 and 19, as well as the complementation of resistance with MdMLO18 in the Arabidopsis thaliana triple mlo mutant Atmlo2/6/12. The knock-down of MdMLO19 reduced PM disease severity by 75%, whereas the knock-down of MdMLO11, alone or in combination with MdMLO19, did not result in any reduction or additional reduction of susceptibility compared with MdMLO19 alone. The test in A. thaliana excluded a role for MdMLO18 in PM susceptibility. Cell wall appositions (papillae) were present in both PM-resistant and PM-susceptible plants, but were larger in resistant lines. No obvious negative phenotype was observed in plants with mlo genes knocked down. Apparently, MdMLO19 plays the pivotal role in apple PM susceptibility and its knock-down induces a very significant level of resistance. PMID- 26997490 TI - A Novel Index Combining Diastolic and Systolic Tissue Doppler Parameters for Prediction of Atrial Fibrillation Recurrence. AB - OBJECTIVE: Identification of patients at risk for atrial fibrillation (AF) recurrence with using simple and objective parameters may be helpful in tailoring the treatment. In this study, we investigated whether E/(Ea*Sa) and Ea/(Aa*Sa) could be a predictor of AF recurrence after cardioversion. (E = early diastolic transmitral velocity, Ea = early diastolic mitral annular velocity, Aa = late diastolic mitral annular velocity, Sa = systolic mitral annular velocity). METHODS: In total, 127 patients with persistent AF were evaluated for this study and 73 patients were included according to the study criteria. Sinus rhythm (SR) was achieved for 70 patients after electrical direct-current cardioversion. E, Sa, Ea, and Aa were determined at mitral medial and lateral site and average values obtained. E/(Ea*Sa) and Ea/(Aa*Sa) were calculated (medial, lateral, average). Heart rate and rhythm were followed with an electrocardiography (ECG) monitor and 12-lead ECG at first week and first month. RESULTS: At one month, 53 patients (75.7%) were in SR, whereas 17 patients (24.3%) reverted to AF. According to precardioversion E/(Ea*Sa) lateral, E/(Ea*Sa) medial, E/(Ea*Sa) average (P <= 0.01 for all the indices), 24-hour echocardiographic evaluation E/(Ea*Sa) lateral, E/(Ea*Sa) medial, E/(Ea*Sa) average, Ea/(Aa*Sa) lateral, Ea/(Aa*Sa) medial, and Ea/(Aa*Sa) average (P <= 0.01 for all the indices), indices were significantly higher in the AF recurrence group than in the SR group. Furthermore, the ROC analysis showed that all the E/(Ea*Sa) and Ea/(Aa*Sa) parameters predict the AF recurrence. The AUC values range from 70% to 81% (P <= 0.01 for all the parameters). In subgroup analysis of the patients, precardioversion mitral medial E/Ea ratio was between 8 and 15, and the ROC analysis showed that the novel indices predict the AF recurrence. The AUC values range from 72% to 86% (P <= 0.02 for all the parameters). CONCLUSIONS: We found that E/(Ea*Sa) and Ea/(Aa*Sa) indices are novel predictors of AF recurrence. PMID- 26997491 TI - Up regulation of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is associated with intestinal epithelial cells apoptosis in TNBS-induced experimental colitis. AB - Glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which exists mainly in the liver, is a D-2-hydroxy-acid dehydrogenase that plays a critical role in the formation of primary hyperoxaluria type 2 (PH2). Here, we investigated GRHPR expression and its potential role in both human Crohn's disease (CD) and experimental colitis. Murine experimental colitis models were established by administration of trinitrobenzenesulphonic acid (TNBS). As shown by Western blot, significant up-regulation of GRHPR was found in TNBS-treated mice as compared with normal controls. Immunohistochemistry (IHC) also showed increased GRHPR expression, and the molecule was located in intestinal epithelial cells (IECs). This phenomenon also occurred in patients with Crohn's disease. Besides, in an in vitro study, human IEC line HT-29 cells cultured with tumor necrosis factor alpha (TNF-alpha) were used to evaluate the changes in expression of GRHPR. Moreover, overexpression of GRHPR was accompanied by active caspase-3 and cleaved poly ADP ribose polymerase (PARP) accumulation. Furthermore, knock-down GRHPR could inhibit the accumulation of active caspase-3 and cleaved PARP as shown by Western blot in TNF-alpha treated HT-29 cells. Flow cytometry assay indicated that interference of GRHPR led to increasing apoptosis of IECs. These data suggested that GRHPR might exert its pro-apoptosis function in IECs. Thus, GRHPR might play an important role in regulating IECs apoptosis, and might be a potential therapeutic target for CD. PMID- 26997492 TI - The expression of osteopontin and vascular endothelial growth factor in correlation with angiogenesis in monoclonal gammopathy of undetermined significance and multiple myeloma. AB - Several studies have shown a gradual increase in the extent of bone marrow angiogenesis in various stages of proliferative plasma cell disorders, from monoclonal gammopathy of undetermined significance (MGUS) to active multiple myeloma (MM). The main aim of this study was to evaluate tumor angiogenesis parameters in detail and to correlate them with the expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in the bone marrow of patients with MGUS and MM. In addition, we wanted to determine their prognostic significance in active MM. Ninety-five patients were enrolled in the study: 14 diagnosed with MGUS, 13 with asymptomatic myeloma (AMM) and 68 with active MM. Computer assisted image analysis was used to determine the angiogenesis parameters, the quantity of microvessels per 1mm(2) (MVD), the area occupied by microvessels per 1mm(2) and the percentage of microvessel area in total section area (TVA). Double immunohistochemical methods CD138+VEGF and CD138+OPN were used to evaluate expression of these proteins in plasma cells, and OPN was also analyzed for its interstitial expression (iOPN). A significant positive correlation was determined between VEGF and iOPN with angiogenic parameters in the MGUS stage of the disease. In advanced stages of the disease, a significant negative correlation was recorded between OPN and iOPN with parameters of angiogenesis. Overall survival was significantly shorter for patients with negative iOPN (p=0.002) and higher angiogenic parameters, MVD (p=0.009), TVA (p=0.008) and area of microvessels per 1mm(2) (p=0.02). Positive VEGF expression in our model predicted a better three-year survival of patients with active MM (OR: 5.25, p=0.03; HR: 0.44, p=0.04). The results of our study suggested a possible key role of VEGF and OPN in the induction of angiogenesis in early-stage disease. PMID- 26997493 TI - Diagnosis of acute coronary occlusion in patients with non-STEMI by point-of-care echocardiography with speckle tracking. PMID- 26997494 TI - Warm-up Brugada phenocopy associated with takotsubo cardiomyopathy. PMID- 26997495 TI - Which measures of cigarette dependence are predictors of smoking cessation during pregnancy? Analysis of data from a randomized controlled trial. AB - AIMS: To examine the ability of different common measures of cigarette dependence to predict smoking cessation during pregnancy. DESIGN: Secondary analysis of data from a parallel-group randomized controlled trial of physical activity for smoking cessation. The outcomes were biochemically validated smoking abstinence at 4 weeks post-quit and end-of-pregnancy. SETTING: Women identified as smokers in antenatal clinics in 13 hospital trusts predominantly in southern England, who were recruited to a smoking cessation trial. PARTICIPANTS: Of 789 pregnant smokers recruited, 784 were included in the analysis. MEASUREMENTS: Using random effect logistic regression models, we analysed the effects of baseline measures of cigarette dependence, including numbers of cigarettes smoked daily, Fagerstrom Test of Cigarette Dependence (FTCD) score, the two FTCD subscales of Heaviness of Smoking Index (HSI) and non-Heaviness of Smoking Index (non-HSI), expired carbon monoxide (CO) level and urges to smoke (strength and frequency) on smoking cessation. Associations were adjusted for significant socio-demographic/health behaviour predictors and trial variables, and area under the receiver operating characteristic (ROC) curve was used to determine the predictive ability of the model for each measure of dependence. FINDINGS: All the dependence variables predicted abstinence at 4 weeks and end-of-pregnancy. At 4 weeks, the adjusted odds ratio (OR) (95% confidence interval) for a unit standard deviation increase in FTCD was 0.59 (0.47-0.74), expired CO = 0.54 (0.41-0.71), number of cigarettes smoked per day 0.65 (0.51-0.84) and frequency of urges to smoke 0.79 (0.63-0.98); at end-of-pregnancy they were: 0.60 (0.45-0.81), 0.55 (0.37-0.80), 0.70 (0.49 0.98) and 0.69 (0.51-0.94), respectively. HSI and non-HSI exhibited similar results to the full FTCD. CONCLUSIONS: Four common measures of dependence, including number of cigarettes smoked per day, scores for Fagerstrom Test of Cigarette Dependence and frequency of urges and level of expired CO, all predicted smoking abstinence in the short term during pregnancy and at end-of pregnancy with very similar predictive validity. PMID- 26997496 TI - Exposure to sucrose during periods of withdrawal does not reduce cocaine-seeking behavior in rats. AB - Concomitant access to drugs of abuse and alternative rewards such as sucrose has been shown to decrease addiction-related behaviors in animals. Here we investigated whether access to sucrose during abstinence in contexts that are temporally and physically distinct from drug-related contexts could reduce subsequent drug seeking. In addition, we investigated whether a history of cocaine self-administration would alter the rewarding effects of sucrose. Rats self-administered cocaine for ten sessions, while yoked-saline rats received only saline injections, and then we subjected them to a 30-day withdrawal period during which they had access to water and sucrose continuously or intermittently according to a schedule that induces binge-drinking behavior. At the end of the withdrawal period, rats were tested for cocaine seeking behavior during a single 6 h session. We found that exposure to cocaine increased sucrose consumption only when rats had intermittent access to sucrose, but exposure to sucrose did not alter drug seeking regardless of the schedule of access. These results suggest that exposure to cocaine cross-sensitizes to the rewarding effects of sucrose, but exposure to sucrose during abstinence, temporally and physically distinct from drug-related environments, does not to reduce drug seeking. PMID- 26997497 TI - Clinical outcomes and prevalence of cancer in patients with possible groove pancreatitis. AB - BACKGROUND AND AIM: Data on non-surgical treatment of groove pancreatitis (GP) and the risk of cancer are lacking. We aimed to determine the prevalence and predictors of cancer in patients in whom the diagnosis GP was considered, and to evaluate symptom improvement after treatment. STUDY: Patients referred with possible GP (2001-2014) were retrospectively included. An experienced radiologist reassessed imaging. GP patients received questionnaires evaluating their symptoms. RESULTS: From the 38 possible GP patients, 10 had cancer (26%) and 28 GP (74%). Compared with cancer patients, GP patients more frequently had cysts (2/10 vs. 18/28, P = 0.03), less often jaundice (6/10 vs 3/27, P < 0.01), an abrupt caliber change of the CBD (5/10 vs. 2/28, P < 0.01) or suspicious cytology (5/9 vs 2/20, P = 0.02). Of the 28 GP patients, 14 patients were treated conservatively of whom 12 reported symptom improvement after a median follow-up of 45 months (range 7-127 months). All 6 patients treated endoscopically and 7/8 patients treated surgically reported symptom improvement. Surgery, performed because of treatment failure (3/8) or inability to exclude malignancy (5/8), caused mortality in 1/8 patients. CONCLUSIONS: Suspicion of pancreatic cancer should be high in patients presenting with possible GP. Conservative, endoscopic and surgical treatment can all lead to symptom improvement, suggesting a 'step-up approach' to GP once cancer is excluded. PMID- 26997498 TI - Dietary pattern and breast cancer risk in Japanese women: the Japan Public Health Center-based Prospective Study (JPHC Study). AB - Evidence that diet is associated with breast cancer risk is inconsistent. Most of the studies have focused on risks associated with specific foods and nutrients, rather than overall diet. In this study, we aimed to evaluate the association between dietary patterns and breast cancer risk in Japanese women. A total of 49 552 Japanese women were followed-up from 1995 to 1998 (5-year follow-up survey) until the end of 2012 for an average of 14.6 years. During 725 534 person-years of follow-up, 718 cases of breast cancer were identified. We identified three dietary patterns (prudent, westernised and traditional Japanese). The westernised dietary pattern was associated with a 32 % increase in breast cancer risk (hazard ratios (HR) 1.32; 95 % CI 1.03, 1.70; P trend=0.04). In particular, subjects with extreme intake of the westernised diet (quintile (Q) Q5_5th) had an 83 % increase in risk of breast cancer in contrast to those in the lowest Q1 (HR 1.83; 95 % CI 1.25, 2.68; P trend=0.01). In analyses stratified by menopausal status, postmenopausal subjects in the highest quintile of the westernised dietary pattern had a 29 % increased risk of breast cancer (HR 1.29; 95 % CI 0.99, 1.76; P trend=0.04). With regard to hormone receptor status, the westernised dietary pattern was associated with an increased risk of oestrogen receptor positive/progesterone receptor-positivetumours (HR 2.49; 95 % CI 1.40, 4.43; P trend<0.01). The other dietary patterns were not associated with the risk of breast cancer in Japanese women. A westernised dietary pattern is associated with an increased risk of breast cancer in Japanese women. PMID- 26997499 TI - DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress. AB - During apoptosis mitochondria undergo cristae remodeling and fragmentation, but how the latter relates to outer membrane permeabilization and downstream caspase activation is unclear. Here we show that the mitochondrial fission protein Dynamin Related Protein (Drp) 1 participates in cytochrome c release by selected intrinsic death stimuli. While Bax, Bak double deficient (DKO) and Apaf1(-/-) mouse embryonic fibroblasts (MEFs) were less susceptible to apoptosis by Bcl-2 family member BID, H(2)O(2), staurosporine and thapsigargin, Drp1(-/-) MEFs were protected only from BID and H(2)O(2). Resistance to cell death of Drp1(-/-) and DKO MEFs correlated with blunted cytochrome c release, whereas mitochondrial fragmentation occurred in all cell lines in response to all tested stimuli, indicating that other mechanisms accounted for the reduced cytochrome c release. Indeed, cristae remodeling was reduced in Drp1(-/-) cells, potentially explaining their resistance to apoptosis. Our results indicate that caspase-independent mitochondrial fission and Drp1-dependent cristae remodeling amplify apoptosis. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID- 26997500 TI - Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan? AB - Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the aging process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artifacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect aging and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan. In this review, I discuss the latest literature focused on the role of mitochondrial ROS in aging, and how these new discoveries are helping to better understand the role of mitochondria in health and disease. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID- 26997502 TI - Nanoparticle Capping Agent Controlled Electron-Transfer Dynamics in Ionic Liquids. AB - Herein, we report a change in the mechanism of the oxidation of silver nanoparticles (Ag NPs) with the molecular weight of a poly(ethylene) glycol (PEG) capping agent. Characterisation of the modified nanoparticles is undertaken using dynamic light scattering and UV/Vis spectroscopy. Electrochemical analyses reveal that the oxidation of 6000 molecular weight (MW) PEG is consistent with a polymer gated mechanism, whilst for 2000 MW PEG the polymer does not hinder the oxidation. The 10,000 MW PEG Ag NPs are rendered almost electrochemically inactive. This study demonstrates the ability to alter and better understand the electron-transfer mechanism in a room temperature ionic liquid (RTIL) by systematically altering the capping agent. PMID- 26997503 TI - Total synthesis of protosappanin A and its derivatives via palladium catalyzed ortho C-H activation/C-C cyclization under microwave irradiation. AB - A total synthesis method for protosappanin A, which is a complex natural product with many biological activities, was developed with 6 linear steps. Dibenzo[b,d]oxepinones as the key intermediates of the synthetic route were prepared by a palladium-catalyzed ortho C-H activation/C-C cyclization under microwave irradiation. 25 derivatives of protosappanin A were obtained. PMID- 26997501 TI - Retrograde signaling: Organelles go networking. AB - The term retrograde signaling refers to the fact that chloroplasts and mitochondria utilize specific signaling molecules to convey information on their developmental and physiological states to the nucleus and modulate the expression of nuclear genes accordingly. Signals emanating from plastids have been associated with two main networks: 'Biogenic control' is active during early stages of chloroplast development, while 'operational' control functions in response to environmental fluctuations. Early work focused on the former and its major players, the GUN proteins. However, our view of retrograde signaling has since been extended and revised. Elements of several 'operational' signaling circuits have come to light, including metabolites, signaling cascades in the cytosol and transcription factors. Here, we review recent advances in the identification and characterization of retrograde signaling components. We place particular emphasis on the strategies employed to define signaling components, spanning the entire spectrum of genetic screens, metabolite profiling and bioinformatics. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID- 26997504 TI - [Scientific communications at the 20th "Journees de neurologie de langue francaise"]. PMID- 26997505 TI - Therapeutic Modulation of Glutamate Receptors in Major Depressive Disorder. AB - Current pharmacotherapies for major depressive disorder (MDD) have a distinct lag of onset that can prolong distress and impairment for patients, and realworld effectiveness trials further suggest that antidepressant efficacy is limited in many patients. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms, e.g., receptor/reuptake agonists or antagonists with varying affinities for serotonin, norepinephrine, or dopamine. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, as well as in the development of novel therapeutics for this disorder. Since the rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000, other NMDA receptor antagonists have been studied in MDD. These have been associated with relatively modest antidepressant effects compared to ketamine, but some have shown more favorable characteristics with increased potential in clinical practice (for instance, oral administration, decreased dissociative and/or psychotomimetic effects, and reduced abuse/diversion liability). This article reviews the clinical evidence supporting the use of glutamate receptor modulators with direct affinity for cognate receptors: 1) non-competitive NMDA receptor antagonists (ketamine, memantine, dextromethorphan, AZD6765); 2) subunit (NR2B)-specific NMDA receptor antagonists (CP- 101,606/traxoprodil, MK-0657); 3) NMDA receptor glycine-site partial agonists (D-cycloserine, GLYX- 13); and 4) metabotropic glutamate receptor (mGluR) modulators (AZD2066, RO4917523/basimglurant). Several other theoretical glutamate receptor targets with preclinical antidepressant-like efficacy, but that have yet to be studied clinically, are also briefly discussed; these include alpha-amino-3-hydroxyl-5-methyl-4- isoxazoleproprionic acid (AMPA) agonists, mGluR2/3 negative allosteric modulators, and mGluR7 agonists. PMID- 26997508 TI - A dizygotic twin pregnancy in a MODY 3-affected woman. AB - BACKGROUND: MODY diabetes includes rare familiar forms due to genetic mutations resulting in beta-cell dysfunction. MODY 3 is due to mutations in the gene transcription factor HNF-1alpha, with diabetes diagnosis in adolescence or early adult life. Few data are available about MODY 3 in pregnancy. CASE REPORT: A 36 year-old Italian woman came to our unit at the 5th week of pregnancy. She was diagnosed with diabetes at 18 years, with negative autoimmunity and a strong familiarity for diabetes. She was treated with gliclazide and metformin. She had a previous pregnancy in which she was treated with insulin, giving birth at 38 weeks to a 3.210 kg baby girl, who showed neonatal hypoglycemia. We switched her to insulin treatment according to guidelines. We asked for genetic molecular testing, resulting in a HNF-1alpha gene mutation. A US examination at 7 weeks revealed a twin, bicorial, biamniotic pregnancy. At 37 weeks of gestation, she gave birth to two normal-weight baby girls; only one showed neonatal hypoglycemia and a genetic test revealed that she was affected by HNF-1alpha gene mutation. Subsequently, entire family of the woman was tested, showing that the father, the sister and the first daughter had the same HNF-1alpha mutation. DISCUSSION: A MODY 3 foetus needs a near-normal maternal glycemic control, because the exposure to intrauterine hyperglycemia can lead to an earlier age of diabetes onset. Neonatal hypoglycemia is generally observed in MODY 1 infants, but it is possible to hypothesize that some HNF-1alpha mutations could lead to a functionally impaired protein that might dysregulate HNF-4alpha expression determining hypoglycemia. PMID- 26997507 TI - The Development of Rapastinel (Formerly GLYX-13); A Rapid Acting and Long Lasting Antidepressant. AB - BACKGROUND: Rapastinel (GLYX-13) is a NMDA receptor modulator with glycine-site partial agonist properties. It is a robust cognitive enhancer and shows rapid and long-lasting antidepressant properties in both animal models and in humans. METHODS: Rapastinel was derived from a monoclonal antibody, B6B21, is a tetrapeptide (threonine-proline-proline-threonine-amide) obtained from amino acid sequence information obtained from sequencing one of the hypervariable regions of the light chain of B6B21. The in-vivo and in-vitro pharmacology of rapastinel was examined. RESULTS: Rapastinel was found to be a robust cognitive enhancer in a variety of learning and memory paradigms and shows marked antidepressant-like properties in multiple models including the forced swim (Porsolt), learned helplessness and chronic unpredictable stress. Rapastinel's rapid-acting antidepressant properties appear to be mediated by its ability to activate NMDA receptors leading to enhancement in synaptic plasticity processes associated with learning and memory. This is further substantiated by the increase in mature dendritic spines found 24 hrs after rapastinel treatment in both the rat dentate gyrus and layer five of the medial prefrontal cortex. Moreover, ex vivo LTP studies showed that the effects of rapastinel persisted at least two weeks post dosing. CONCLUSION: These data suggest that rapastinel has significant effects on metaplasticity processes that may help explain the long lasting antidepressant effects of rapastinel seen in the human clinical trial results. PMID- 26997506 TI - Autophagy in Diabetic Retinopathy. AB - Autophagy is an important homeostatic cellular process encompassing a number of consecutive steps indispensable for degrading and recycling cytoplasmic materials. Basically autophagy is an adaptive response that under stressful conditions guarantees the physiological turnover of senescent and impaired organelles and, thus, controls cell fate by various cross-talk signals. Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and accounts for 5% of all blindness. Although, various metabolic disorders have been linked with the onset of DR, due to the complex character of this multi-factorial disease, a connection between any particular defect and DR becomes speculative. Diabetes increases inflammation, advanced glycation end products (AGEs) and oxidative stress in the retina and its capillary cells. Particularly, a great number of evidences suggest a mutual connection between oxidative stress and other major metabolic abnormalities implicated in the development of DR. In addition, the intricate networks between autophagy and apoptosis establish the degree of cellular apoptosis and the progression of DR. Growing data underline the crucial role of reactive oxygen species (ROS) in the activation of autophagy. Depending on their delicate balance both redox signaling and autophagy, being detrimental or beneficial, retain opposing effects. The molecular mechanisms of autophagy are very complex and involve many signaling pathways cooperating at various steps. This review summarizes recent advances of the possible molecular mechanisms in autophagic process that are involved in pathophysiology of DR. In depth analysis on the molecular mechanisms leading to autophagy in the retinal pigment epithelial (RPE) will be helpful to plan new therapies aimed at preventing or improving the progression of DR. PMID- 26997509 TI - Potential role of Hsp90 in rat islet function under the condition of high glucose. AB - AIMS: The preservation of pancreatic beta-cell function is a key point in the treatment of type 2 diabetes mellitus. There is substantial evidence demonstrating that heat-shock protein 90 (Hsp90) is needed for the stabilization and correct folding of client proteins and plays important roles in various biological processes. Here, we revealed the important role of Hsp90 in beta-cell function. METHODS: Islets from male Sprague-Dawley rats were isolated to be used for further RT-PCR, Western blot, and insulin secretion test ex vivo in response to different stimuli. RESULTS: Our results revealed that Hsp90 expression was significantly decreased in isolated rat islets exposed to high glucose, which was involved in glucokinase activation and glucose metabolism, not calcium signaling. Two kinds of Hsp90 inhibitors 17-DMAG and CCT018159 markedly enhanced glucose stimulated insulin secretion from rat islets, along with increased expressions of genes closely related to beta-cell function. CONCLUSIONS: These data indicate that Hsp90 may be involved in high glucose-induced islet function adaptation. PMID- 26997510 TI - The incidence rate and prevalence of pediatric type 1 diabetes mellitus (age 0 18) in the Italian region Friuli Venezia Giulia: population-based estimates through the analysis of health administrative databases. AB - AIMS: The main objective of this study was to estimate the incidence rate and prevalence of pediatric type 1 diabetes mellitus (T1DM; population 0-18 years of age) in the northeastern Italian region Friuli Venezia Giulia and to characterize the subjects affected by the disease. METHODS: This was a retrospective population-based study conducted through the individual-level linkage of several health administrative databases of the Friuli Venezia Giulia region. The incidence rate and prevalence were calculated in the population 0-18 years of age. Using the Mid-p exact method, 95 % confidence intervals for rates were calculated. RESULTS: The incidence rate of pediatric T1DM in the years 2010-2013 was 15.8 new cases/100,000 person-years, peaking in the age class 10-14 years. The rate has increased substantially as compared with the previous regional estimate that dated back to 1993. We observed a seasonal pattern both in the date of birth of the incident cases and in the date of onset of the disease. In the region in 2013, there were 294 prevalent cases (15.1/10,000 inhabitants). Most of them had at least one glycated hemoglobin test in the year. More than 15 % had co existing autoimmune comorbidities. CONCLUSIONS: The incidence rate of pediatric T1DM in Friuli Venezia Giulia has increased in the last years, and the disease is a relevant public health issue in the region. PMID- 26997511 TI - Prior knowledge of blood glucose meter download improves the accuracy of verbal self-reported blood glucose in teenagers with type I diabetes at ski camp. AB - AIMS: Despite advances in diabetes management, self-monitoring of blood glucose (SMBG) remains fundamental. A number of studies, principally in adults, have confirmed that logbook entries and verbal SMBG reports are prone to common errors. In the context of an adolescent diabetes camp, the accuracy of verbally reported SMBG is crucial for guiding safe therapeutic management, and negating the risk of exercise-induced hypoglycemia. We aimed to assess whether awareness of a planned meter download at the completion of a diabetes camp would improve the overall accuracy of verbally reported SMBG. METHODS: Adolescents with type one diabetes (n = 26) attended a 3-day ski camp in 2014. Verbally reported SMBG values were recorded by camp supervisors at multiple time points throughout the camp. The intervention involved ensuring that all participants (at camp commencement) were aware of a planned meter download and SMBG review at camp conclusion. These data were then compared with historical camp data from 2012, collected using identical methodology, in which participants (n = 20) were unaware of the planned meter download. For analysis, blood glucose (BGL) data were classified as: matching, phantom (verbal SMBG value with no corresponding meter download value), and over- or underestimate (verbally reported value >/< meter downloaded value). RESULTS: Dual data regarding verbal SMBG and meter downloads were obtained on 550 instances of BGL testing during the 2014 camp (the intervention group). This was compared to dual data for 396 historical tests from the 2012 control group. For the intervention group, the overall error rate was 4.7 %, over 34 % of participants. There was a statistically significant improvement in accuracy compared to historical nonintervention data, in which there was an error rate of 14.1 % over 70 % of participants (p < 0.001). There was also a decrease in phantom readings to 2 %, from 8.6 % in 2012 (p < 0.001). CONCLUSIONS: This study demonstrates an improvement in accuracy and reliability of verbally reported SMBG, following a simple intervention of ensuring participants were aware of a meter download at the completion of camp. This intervention could be easily incorporated into adolescent diabetes camp safety protocols and may provide an easy, low-cost way of improving verbally reported SMBG accuracy and therefore safety on camp. PMID- 26997512 TI - A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients. AB - AIMS: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. METHODS: Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. RESULTS: A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23-3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83-1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03-1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54-1.42); P = 0.583), or with PDR for either type of DM. CONCLUSIONS: Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM. PMID- 26997515 TI - Sparse Data Necessitate Explicit Treatment of Beta-Diversity: A Reply to Bush et al. PMID- 26997514 TI - Cost Variation in Diabetes Care across Dutch Care Groups? AB - OBJECTIVE: The introduction of bundled payment for diabetes care in the Netherlands led to the origination of care groups. This study explored to what extent variation in health care costs per patient can be attributed to the performance of care groups. Furthermore, the commonly applied simple mean aggregation was compared with the more advanced generalized linear mixed model (GLMM) to benchmark health care costs per patient between care groups. DATA SOURCE: Dutch 2009 nationwide insurance claims data of diabetes type 2 patients (104,544 patients, 50 care groups). STUDY DESIGN: Both a simple mean aggregation and a GLMM approach was applied to rank care groups, using two different health care costs variables: total treatment health care costs and diabetes-specific specialist care costs per diabetes patient. PRINCIPAL FINDINGS: Care groups varied slightly in the first and mainly in the second indicator. Care group variation was not explained by composition. Although the ranking methods were correlated, some care groups' rank positions differed, with consequences on the top-10 and the low-10 positions. CONCLUSIONS: Differences between care groups exist when an appropriate indicator and a sophisticated aggregation technique is used. Currently applied benchmarking may have unfair consequences for some care groups. PMID- 26997513 TI - Various Cell Populations Within the Mononuclear Fraction of Bone Marrow Contribute to the Beneficial Effects of Autologous Bone Marrow Cell Therapy in a Rodent Stroke Model. AB - Cell-based therapies including bone-marrow derived mononuclear cells (MNCs) are now widely being studied because of their pleotropic effects and promising results to improve recovery after stroke in animal models. Unlike other types of cell therapies, MNCs is a mixture of lymphoid, myeloid, erythroid, and stem cell populations. Which cell population(s) accounts for the beneficial effects of MNCs in stroke recovery is unclear. In this paper, we employed a mouse stroke model with middle cerebral artery occlusion (MCAo), and used positively and negatively sorted autologous MNCs by MACs to determine which fractions of the MNCs contribute to their beneficial effects. We evaluated the benefits of neurofunctional recovery produced by individual cell lineages within MNCs in a long-term observation study up to 28 days after stroke. Mortality and modulation of inflammation were also compared among different sub-populations. We further studied the impact of neurotoxicity posed by activated microglia in the presence of different cell lineages within MNCs. We concluded that myeloid cell lineage and stem cell/progenitors appeared to be important components within MNCs that contribute to improved outcomes after stroke. PMID- 26997516 TI - Musculoskeletal anatomy of the Eurasian lynx, Lynx lynx (Carnivora: Felidae) forelimb: Adaptations to capture large prey? AB - Mammalian carnivores adhere to two different feeding strategies relative to their body masses. Large carnivores prey on animals that are the same size or larger than themselves, whereas small carnivores prey on smaller vertebrates and invertebrates. The Eurasian lynx (Lynx lynx) falls in between these two categories. Lynx descend from larger forms that were probably large prey specialists, but during the Pleistocene became predators of small prey. The modern Eurasian lynx may be an evolutionary reversal toward specializing in large prey again. We hypothesized that the musculoskeletal anatomy of lynx should show traits for catching large prey. To test our hypothesis, we dissected the forelimb muscles of six Eurasian lynx individuals and compared our findings to results published for other felids. We measured the bones and compared their dimensions to the published material. Our material displayed a well-developed pectoral girdle musculature with some uniquely extensive muscle attachments. The upper arm musculature resembled that of the pantherine felids and probably the extinct sabertooths, and also the muscles responsible for supination and pronation were similar to those in large cats. The muscles controlling the pollex were well developed. However, skeletal indices were similar to those of small prey predators. Our findings show that lynx possess the topographic pattern of muscle origin and insertion like in large felids. J. Morphol. 277:753-765, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26997517 TI - Estimands: discussion points from the PSI estimands and sensitivity expert group. AB - ICH E9 Statistical Principles for Clinical Trials was issued in 1998. In October 2014, an addendum to ICH E9 was proposed relating to estimands and sensitivity analyses. In preparation for the release of the addendum, Statisticians in the Pharmaceutical Industry held a 1-day expert group meeting in February 2015. Topics debated included definition, development, implementation, education and communication challenges associated with estimands and sensitivity analyses. The topic of estimands is an important and relatively new one in clinical development. A clear message from the meeting was that estimands bridge the gap between study objectives and statistical methods. When defining estimands, an iterative process linking trial objectives, estimands, trial design, statistical and sensitivity analysis needs to be established. Each objective should have at least one distinct estimand, supported by sensitivity analyses. Because clinical trials are multi-faceted and expensive, it is unrealistic to restrict a study to a single objective and associated estimand. The actual set of estimands and sensitivity analyses for a study will depend on the study objectives, the disease setting and the needs of the various stakeholders. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26997518 TI - Systemic adjuvant therapy for renal cell carcinoma: Any hope for future clinical trials? AB - The role of adjuvant therapy for renal cell carcinoma (RCC) after surgical resection has been evaluated in numerous randomized and nonrandomized studies using systemic therapies with distinct mechanisms of action. However, adjuvant therapy has not demonstrated definitive benefit to date and guidelines currently do not support its use. Continued advancement in the understanding of the molecular pathogenesis in RCC is critical, which would lead to identification of new therapeutic targets, as well as novel prognostic and predictive biomarkers, in hopes of improving outcomes in this lethal disease. Herein we summarize the results of randomized studies of the adjuvant treatments of RCC, in hopes to direct future effort in the development of treatment of this disease. PMID- 26997520 TI - A study on the association between hyperlipidemia and hypothyroidism and the response to TKIs in metastatic renal cell carcinoma. AB - AIM: Vascular endothelial growth facto receptor-tyrosine kinase inhibitors (VEGFR TKIs) are widely used for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the association between the response to VEGFR-TKIs and hyperlipidemia and hypothyroidism. METHODS: Clinical data on 155 patients with mRCC treated with VEGFR-TKIs at the Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were retrospectively analyzed. All patients received first-line TKI therapy. Survival analysis was performed with a significance level of 0.05 using a Kaplan-Meier curve. The chi(2) test was used for the intergroup comparison. The Cox regression model was used for the analysis of multiple factors affecting survival. RESULTS: The median survival for the whole group (n = 155) was 36.2 months. A total of 57 patients (36.8 percent) developed hypothyroidism and 85 patients (54.9 percent) experienced hyperlipidemia. The response rate (RR) and median progression-free survival (mPFS) for patients with normal thyroid function were 32.7 percent and 9.1 months, respectively, 54.5 percent and 13.7 months with grade I hypothyroidism, 70.8 percent and 23.8 months with grade II hypothyroidism (P values of 0.001 and 0.017, respectively). The RR and mPFS for patients with normal blood lipids were 23.9 percent and 8.0 months, respectively, 54.0 percent and 12.9 months with grade I hyperlipidemia, 60.7 percent and 14.0 months with grade II hyperlipidemia, and 100.0 percent and 22.2 months with grade III hyperlipidemia. Significant differences in the RR and mPFS were seen between groups (the P values were 0.000 and 0.005, respectively). CONCLUSION: Hypothyroidism or hyperlipidemia may be effective predictive factors for response to treatment with VEGFR-TKIs in mRCC patients. Large-sample studies are warranted to further prove these results. PMID- 26997521 TI - Synthesis of MoS2 @C Nanotubes Via the Kirkendall Effect with Enhanced Electrochemical Performance for Lithium Ion and Sodium Ion Batteries. AB - A MoS2 @C nanotube composite is prepared through a facile hydrothermal method, in which the MoS2 nanotube and amorphous carbon are generated synchronically. When evaluated as an anode material for lithium ion batteries (LIB), the MoS2 @C nanotube manifests an enhanced capacity of 1327 mA h g(-1) at 0.1 C with high initial Coulombic efficiency (ICE) of 92% and with capacity retention of 1058.4 mA h g(-1) (90% initial capacity retention) after 300 cycles at a rate of 0.5 C. A superior rate capacity of 850 mA h g(-1) at 5 C is also obtained. As for sodium ion batteries, a specific capacity of 480 mA h g(-1) at 0.5 C is achieved after 200 cycles. The synchronically formed carbon and stable hollow structure lead to the long cycle stability, high ICE, and superior rate capability. The good electrochemical behavior of MoS2 @C nanotube composite suggests its potential application in high-energy LIB. PMID- 26997519 TI - Targeting Protein-Protein Interactions in the HIF System. AB - Animals respond to chronic hypoxia by increasing the levels of a transcription factor known as the hypoxia-inducible factor (HIF). HIF upregulates multiple genes, the products of which work to ameliorate the effects of limited oxygen at cellular and systemic levels. Hypoxia sensing by the HIF system involves hydroxylase-catalysed post-translational modifications of the HIF alpha-subunits, which 1) signal for degradation of HIF-alpha and 2) limit binding of HIF to transcriptional coactivator proteins. Because the hypoxic response is relevant to multiple disease states, therapeutic manipulation of the HIF-mediated response has considerable medicinal potential. In addition to modulation of catalysis by the HIF hydroxylases, the HIF system manifests other possibilities for therapeutic intervention involving protein-protein and protein-nucleic acid interactions. Recent advances in our understanding of the structural biology and biochemistry of the HIF system are facilitating medicinal chemistry efforts. Herein we give an overview of the HIF system, focusing on structural knowledge of protein-protein interactions and how this might be used to modulate the hypoxic response for therapeutic benefit. PMID- 26997522 TI - Species phylogeny and diversification process of Northeast Asian Pungitius revealed by AFLP and mtDNA markers. AB - Pungitius is a highly diversified genus of sticklebacks (Gasterosteidae) occurring widely in northern parts of the Northern Hemisphere. Several ecologically and genetically divergent types that are largely isolated reproductively but occasionally hybridize in sympatry have been discovered in Northeast Asia, although the taxonomy and evolutionary relationships among them remain unclear. We used amplified fragment length polymorphism (AFLP) and mitochondrial DNA (mtDNA) markers to infer phylogenies among individuals collected from sympatric and allopatric populations, including the type localities of the described species. Phylogenetic analyses based on 2683 polymorphic AFLP loci confirmed seven species, each of which (except for one entirely allopatric species P. platygaster) was clearly differentiated from one or two other sympatric species and constituted a highly supported monophyletic clade with conspecific allopatric populations. The phylogeny showed that two lineages arose early; one gave rise to two species (circumpolar species P. pungitius and Paratethys species P. platygaster) and the other to five species endemic to Northeast Asia (P. sinensis, P. tymensis, P. polyakovi, P. kaibarae, and P. bussei). The brackish-water, freshwater, and Omono types previously discovered in Japan were reidentified as P. pungitius, P. sinensis, and P. kaibarae, respectively. A marked incongruence was noted between the phylogenies of AFLP and mtDNA markers, suggesting the occasional occurrence of hybridization and mtDNA introgression among distinct species. Our results highlight that the marginal seas of Northeast Asia played a key role as barriers to or facilitators of gene flow in the evolution of species diversity of Pungitius concentrated in this region. PMID- 26997523 TI - Phylogenetics and biogeography of the endemic Madagascan millipede assassin bugs (Hemiptera: Reduviidae: Ectrichodiinae). AB - For at least the past 80my, Madagascar, a major biodiversity hotspot, has been isolated from all other landmasses. This long-term isolation, along with geologic and climatic factors within Madagascar and throughout the Indian Ocean, has undoubtedly influenced the evolution of the island's biota. However, few systematic analyses incorporating modern divergence dating and biogeographic analyses have focused on Madagascan insects. The diverse Madagascan millipede assassin bugs (Heteroptera: Reduviidae: Ectrichodiinae) offer an opportunity to contribute to a limited body of insect-related research that explores Madagascar's historical biogeography. A molecular dataset (COI mtDNA and 18S, 28S D2 and D3-D5 rDNAs) for 56 taxa (39 ingroup) and a combined morphological (145 characters) and molecular dataset for 110 taxa (93 ingroup) are analyzed with maximum likelihood (ML) and parsimony approaches. Based on the molecular ML phylogeny, divergence times were estimated using fossil and secondary calibrations and biogeographic analyses performed using DIVA, DEC, and DEC+j models to determine the role and patterns of vicariance and dispersal in the origin of Madagascan Ectrichodiinae. Results indicate that Ectrichodiinae in Madagascar do not form a monophyletic group, different clades are closely related to Afrotropical and Oriental lineages, and have colonized the island via transoceanic dispersal at least twice from the Oriental region and once from the Afrotropical region in the last ~68my. Additionally, the DEC+j and DIVA models infer a single out-of-Madagascar dispersal event to the Afrotropical region. Oceanic and geologic factors that may have facilitated dispersal between these three regions are discussed. Results of the combined analyses are used to explore character support for Madagascan taxa and inform taxonomic diagnoses. Our results are congruent with the small but growing body of biogeographic research supporting Cenozoic transoceanic dispersal for Madagascan invertebrates to and from Oriental and Afrotropical regions. PMID- 26997524 TI - Liver Copper Estimation: Does Liver Biopsy Size Really Matter? PMID- 26997526 TI - Influence of molecular architecture on the entanglement network: topological analysis of linear, long- and short-chain branched polyethylene melts via Monte Carlo simulations. AB - We present detailed results on the effect of chain branching on the topological properties of entangled polymer melts via an advanced connectivity-altering Monte Carlo (MC) algorithm. Eleven representative model linear, short-chain branched (SCB), and long-chain branched (LCB) polyethylene (PE) melts were employed, based on the total chain length and/or the longest linear chain dimension. Directly analyzing the entanglement [or the primitive path (PP)] network of the system via the Z-code, we quantified several important topological measures: (a) the PP contour length Lpp, (b) the number of entanglements Zes per chain, (c) the end-to end length of an entanglement strand des, (d) the number of carbon atoms per entanglement strand Nes, and (e) the probability distribution for each of these quantities. The results show that the SCB polymer melts have significantly more compact overall chain conformations compared to the linear polymers, exhibiting, relative to the corresponding linear analogues, (a) ~20% smaller values of (the statistical average of Lpp), (b) ~30% smaller values of , (c) ~20% larger values of , and (d) ~50% larger values of . In contrast, despite the intrinsically smaller overall chain dimensions than those of the linear analogues, the LCB (H-shaped and A3AA3 multiarm) PE melts exhibit relatively (a) 7-8% larger values of , (b) 6-11% larger values of for the H-shaped melt and ~2% smaller values of for the A3AA3 multiarm, (c) 2-5% smaller values of , and (d) 7-11% smaller values of . Several interesting features were also found in the results of the probability distribution functions P for each topological measure. PMID- 26997527 TI - Analysis of migration rate and chemotaxis of human adipose-derived mesenchymal stem cells in response to LPS and LTA in vitro. AB - Mesenchymal stem cells (MSC) are able to stimulate the regeneration of injured tissue. Since bacterial infections are common complications in wound healing, bacterial pathogens and their components come into direct contact with MSC. The interaction with bacterial structures influences the proliferation, differentiation and migratory activity of the MSC, which might be of relevance during regeneration. Studies on MSC migration in response to bacterial components have shown different results depending on the cell type. Here, we analyzed the migration rate and chemotaxis of human adipose-derived MSC (adMSC) in response to the basic cell-wall components lipopolysaccharide (LPS) of Gram-negative bacteria and lipoteichoic acid (LTA) of Gram-positive bacteria in vitro. To this end, we used transwell and scratch assays, as well as a specific chemotaxis assay combined with live-cell imaging. We found no significant influence of LPS or LTA on the migration rate of adMSC in transwell or scratch assays. Furthermore, in the u-slide chemotaxis assay, the stimulation with LPS did not exert any chemotactic effect on adMSC. PMID- 26997525 TI - One-year developmental stability and covariance among oddball, novelty, go/no-go, and flanker event-related potentials in adolescence: A monozygotic twin study. AB - ERP measures may index genetic risk for psychopathology before disorder onset in adolescence, but little is known about their developmental rank-order stability during this period of significant brain maturation. We studied ERP stability in 48 pairs of identical twins (age 14-16 years) tested 1 year apart. Trial-averaged voltage waveforms were extracted from electroencephalographic recordings from oddball/novelty, go/no-go, and flanker tasks, and 16 amplitude measures were examined. Members of twin pairs were highly similar, whether based on ERP amplitude measures (intraclass correlation [ICC] median = .64, range = .44-.86) or three factor scores (all ICCs >= .69) derived from them. Stability was high overall, with 69% of the 16 individual measures generating stability coefficients exceeding .70 and all factor scores showing stability above .75. Measures from 10 difference waveforms calculated from paired conditions within tasks were also examined, and were associated with lower twin similarity (ICC median = .52, .38 .64) and developmental stability (only 30% exceeding .70). In a supplemental analysis, we found significant developmental stability for error-related negativity (range = .45-.55) and positivity (.56-.70) measures when average waveforms were based on one or more trials, and that these values were equivalent to those derived from averages using the current field recommendation, which requires six or more trials. Overall, we conclude that the studied brain measures are largely stable over 1 year of mid- to late adolescence, likely reflecting familial etiologic influences on brain functions pertaining to cognitive control and salience recognition. PMID- 26997528 TI - The development of human mast cells. An historical reappraisal. AB - The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34(+)/CD117(+)/CD13(+)multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation. Stem cell factor (SCF) is a major chemotactic factor for MCs and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of MCs. Because MC maturation is influenced by local microenvironmental factors, different MC phenotypes can develop in different tissues and organs. PMID- 26997529 TI - Volume measurements and fluorescent staining indicate an increase in permeability for organic cation transporter substrates during apoptosis. AB - Extensive membrane blebbing is one of the earliest observable changes in HeLa cells stimulated with apoptosis inducers. Blebbing caused by actinomycin D or camptothecin, but not by anti-Fas antibody, is accompanied by an almost 10% volume increase as measured by transmission-through-dye microscopy. When the experiment is carried out in DMEM medium, the swelling appears to result from activation of amiloride-sensitive channels. Low-sodium choline-, but not N methyl(-)D-glucamine-based, medium, also supports swelling during the blebbing phase of apoptosis; this indicates that the membrane becomes permeable to choline as well. Because choline can enter the cells through organic cation transporters (OCT), we tested three fluorescent dyes (2-[4-(dimethylamino)styryl]-1 methylpyridinium iodide, rhodamine 123 and ethidium bromide) that have been reported to utilize OCT for cell entry. Intact HeLa cells are poorly permeable for these fluorophores, and initially they accumulate on the plasma membranes. Blebbing results in an enhanced penetration of these dyes into the cell interior, as was demonstrated both by direct observation and by FRET. The increased membrane permeability is specific for OCT substrates; the other tested cationic dyes apparently cross the membrane by other routes and exhibit a markedly different behavior. Our results reveal a previously unknown feature of apoptosis and the utility of cationic dyes for studying membrane transport. PMID- 26997530 TI - A new Growing Neural Gas for clustering data streams. AB - Clustering data streams is becoming the most efficient way to cluster a massive dataset. This task requires a process capable of partitioning observations continuously with restrictions of memory and time. In this paper we present a new algorithm, called G-Stream, for clustering data streams by making one pass over the data. G-Stream is based on growing neural gas, that allows us to discover clusters of arbitrary shapes without any assumptions on the number of clusters. By using a reservoir, and applying a fading function, the quality of clustering is improved. The performance of the proposed algorithm is evaluated on public datasets. PMID- 26997532 TI - Allotransplantation of macroencapsulated parathyroid cells as a treatment of severe postsurgical hypoparathyroidism: case report. AB - Persistent hypoparathyroidism, a condition associated with major inconvenience and potential morbidity, is more difficult to treat than other hypofunctional endocrine disorders. Therapeutic alternative in severe postsurgical hypoparathyroidism is allotransplantation of macroencapsulated parathyroid cells. With this technique, it is possible to implant cells or tissues of parathyroid origin to replace them in such patients without immunosuppression. At the present time, durable results have only been reported in parathyroid allotransplantation when immunosuppression to prevent rejection is administered. We report an allotransplant of parathyroid cells in a patient with continuous endovenous requirement of calcium to survive. Macrocapsule containing ~(20 to 30)x106 parathyroid cells was constructed with a polyvinylidine difluoride and implanted into the deep femoral artery. The functional activity of the graft, traced for 3 months, allowed to exclude the parenteral administration of calcium and to compensate symptoms of the disease. SIMILAR CASES PUBLISHED: There have been no more than 3 previous clinical reports of similar parathyroid cell allotransplantation without immunosuppression. PMID- 26997531 TI - Investigation of KIF6 Trp719Arg gene polymorphism in a case-control study of coronary artery disease and non-fatal myocardial infarction in the Eastern Province of Saudi Arabia. AB - BACKGROUND: Kinesin-like protein 6 (KIF6), a member of the kinesin superfamily, is involved in intracellular transport. A few prospective studies have shown the KIF6 variant Trp719Arg (rs20455) to be associated with coronary artery disease (CAD) in Caucasian populations. However, recent genome-wide association studies on CAD have not proven these associations. OBJECTIVES: Since the role of KIF6 719Arg allele in other ethnic populations is largely unknown, we sought to determine whether the KIF6 719Arg allele is associated with CAD in an ethnic Middle Eastern population. DESIGN: Case-control study. SETTING: CAD patients and control subjects from King Fahd Hospital of the University, Al-Khobar, Saudi Arabia. PATIENTS AND METHODS: The study population included angiographically defined CAD patients (n=1002) and controls (n=984) with a normal electrocardiogram. MAIN OUTCOME MEASURE(S): Association of KIF6 Trp719Arg mutation with CAD. RESULTS: The KIF6 Trp719Arg polymorphism was not associated with CAD (OR 0.976, 95% CI 0.861-1.105; P=.704). In addition, KIF6 Trp719Arg polymorphism showed a lack of association even in stratified myocardial infarction patients (n=802) (OR 1.006, 95% CI 0.881-1.148; P=.929) in comparison to controls. CONCLUSIONS: The absence of Trp719Arg polymorphism association with CAD and CAD in stratified myocardial infarction cases indicates that the polymorphism is not associated with an increased risk among CAD patients from the Eastern Province of Saudi Arabia. LIMITATIONS: Unavailability of data on statin usage among the patient population. PMID- 26997533 TI - Retroperitoneal paraganglioma presenting as right-sided varicocele: case report. AB - Varicocele, the most important identifiable pathological cause of male infertility, is rarely observed on the right side. In isolated cases of right sided varicocele, the presence of retroperitoneal masses compressing the inferior vena cava should be considered by further investigation. The retroperitoneal masses that are detected tend to grow rapidly due to their location and may be very large at the time of diagnosis. Soft tissue sarcomas are the most common cause of retroperitoneal masses, while paragangliomas are rare causes. Retroperitoneal paragangliomas should be diagnosed via detection of symptoms caused by hormonal activity, observation of the compression effect of the mass, or incidentally during imaging studies. SIMILAR CASES PUBLISHED: This study presents the first case of retroperitoneal paraganglioma in a 41-year old man as isolated right-sided varicocele that has been described in the published reports. PMID- 26997534 TI - Effect of antibiotics on extracellular protein level in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa PAO1 organisms harbouring different plasmids were cultured in broths containing appropriate antibiotic(s). Extracellular proteins were more abundant in the presence of tetracycline or kanamycin than in the presence of other antibiotics. Zymography revealed that alkaline protease (AprA) production was interfered by these antibiotics. Extracellular proteins were not observed at the same level when AprA-deficient EG03 strains were cultured in the presence of different antibiotics. The extracellular protein levels were dependent on the antibiotics and plasmid derivative groups. Levels of extracellular protein were not significantly different between PAO1 (pBBR1MCS-5) and EG03 (pAprcomp-MCS5), and profiles of the extracellular proteome were comparable. In contrast, the level of EG03 (pBBR1MCS-MCS5) extracellular protein was higher than those observed in the other two strains. These results suggested that although AprA partially contributes to the alteration of extracellular protein level, the effect is limited. PMID- 26997536 TI - Porous cubes constructed by cobalt oxide nanocrystals with graphene sheet coatings for enhanced lithium storage properties. AB - In this manuscript, graphene-encapsulated porous cobalt oxide cubes (Co3O4@G) are fabricated through a facile precipitation reaction with subsequent calcination and a self-assembly process. The synthesized porous Co3O4 cubes anchored in the conductive graphene network can realize superior electrical conductivity, withstand volume variation upon prolonged cycling and shorten the diffusion path of lithium ions. When evaluated as anode materials, the Co3O4@G electrode shows excellent electrochemical properties in terms of both stable cycling performance and good rate capabilities. For example, a reversible discharge capacity of 980 mA h g(-1) is delivered after 80 cycles at a current density of 200 mA g(-1). Introducing a conductive graphene network to modify other metal oxides with poor electric conductivity and large volume excursions is of great interest in the development of lithium ion battery technologies. PMID- 26997535 TI - Deficits in executive functions among youths with autism spectrum disorders: an age-stratified analysis. AB - BACKGROUND: Impaired executive function (EF) is suggested to be one of the core features in individuals with autism spectrum disorders (ASD); however, little is known about whether the extent of worse EF in ASD than typically developing (TD) controls is age-dependent. We used age-stratified analysis to reveal this issue. METHOD: We assessed 111 youths with ASD (aged 12.5 +/- 2.8 years, male 94.6%) and 114 age-, and sex-matched TD controls with Digit Span and four EF tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Span (SSP), Spatial Working Memory (SWM), Stockings of Cambridge (SOC), and Intradimensional/Extradimensional Shift Test (I/ED). RESULTS: Compared to TD controls, youths with ASD performed poorer on the Digit Span, SWM, SOC, and I/ED tasks. The performance of all the tasks improved with age for both groups. Age stratified analyses were conducted due to significant age * group interactions in visuospatial planning (SOC) and set-shifting (I/ED) and showed that poorer performance on these two tasks in ASD than TD controls was found only in the child (aged 8-12 years) rather than the adolescent (aged 13-18 years) group. By contrast, youths with ASD had impaired working memory, regardless of age. The increased magnitude of group difference in visuospatial planning (SOC) with increased task demands differed between the two age groups but no age moderating effect on spatial working memory. CONCLUSIONS: Our findings support deficits in visuospatial working memory and planning in youths with ASD; however, worse performance in set-shifting may only be demonstrated in children with ASD. PMID- 26997537 TI - Clinical Dimensions of Bloating in Functional Gastrointestinal Disorders. AB - BACKGROUND/AIMS: Bloating is common bothersome symptoms and most studies conducted in the Western countries found that bloating was frequently associated with lower gastrointestinal (GI) symptoms but many patients complaint bloating as upper GI symptoms in the clinical setting. This study was conducted to assess the prevalence of bloating, and to identify symptom grouping and finally document the impact of bloating in the diagnosis of functional GI disorders. METHODS: Participants in a comprehensive health-screening cohort were enrolled. They were asked about demographic, medical, and social history and upper and lower GI symptoms by using a validated questionnaire. Factor analysis with principal component analysis method with varimax rotation was used. RESULTS: Among the total of 1050 subjects (mean age, 44.6 +/- 10.2 years; females, 46.4%), significant bloating symptoms were found in 282 (26.9%); the prevalence of functional bloating was 6.9%. Factor analysis revealed a 5-component structure with upper GI symptoms, constipation, diarrhea-predominant irritable bowel syndrome (IBS), constipation-predominant IBS, and fecal incontinence. Abdominal bloating loaded on both the upper GI symptoms (0.51 of loadings) and constipation (0.40). On logistic regression analysis, bloating was more predictable for IBS (OR, 7.5; P < 0.001) than functional dyspepsia (FD; OR, 3.7; P = 0.002). Bloating was more frequently combined with IBS according to their severity, but this association was not detected in patients with FD. CONCLUSIONS: Abdominal bloating is common symptom in about a quarter of patients and appears as upper as well as lower GI symptoms. However, abdominal bloating is more predictable for IBS, especially constipation-predominant IBS, than FD. PMID- 26997539 TI - Epidemiology and natural history of non-alcoholic fatty liver disease. AB - Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD) that leads to progressive liver disease and presents a growing challenge to public health. Because of the increased prevalence of metabolic syndrome and obesity, NAFLD and NASH have expanded to a substantial extent. In NASH patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH is mandatory. Although there is currently no validated test of serum biomarkers available to diagnose NASH, and histologic evaluation with a liver biopsy remains the gold standard, screening for fibrosis is recommended in patients with suspicion of NASH. Clinical prediction models and serum biomarkers for advanced fibrosis have relatively good negative predictive value and can be useful for screening. Also, transient elastography is increasingly available to estimate fibrosis in NASH. Therefore, due to the lack of a reliable and accepted non-invasive diagnostic modality, screening for NASH in the general population is not currently recommended. Better understanding of the natural history of NASH is needed to evaluate the utility and cost-effectiveness of screening. PMID- 26997540 TI - Non-alcoholic fatty liver disease and liver transplantation. AB - Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk. PMID- 26997538 TI - Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease. AB - The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. In this review, we highlight the lipids and carbohydrates that provoke hepatocyte injury and the mechanisms involved in lipotoxicity and glucotoxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment. Through upregulation of proteins involved in various pathways including PKR-like ER kinase (PERK), CCAAT/enhancer-binding homologous protein (CHOP), c-Jun NH2-terminal kinase-1 (JNK), Bcl-2 interacting mediator (BIM), p53 upregulated modulator of apoptosis (PUMA), and eventually caspases, hepatocytes in lipotoxic states ultimately undergo apoptosis. The protective role of certain lipids and possible targets for pharmacological therapy are explored. Finally, we discuss the role of high fructose and glucose diets in contributing to organelle impairment and poor glucose transport mechanisms, which perpetuate hyperglycemia and hyperlipidemia by shunting of excess carbohydrates into lipogenesis. PMID- 26997541 TI - Chromium(VI) bioremediation by probiotics. AB - Chromium is a common mineral in the earth's crust and can be released into the environment from anthropogenic sources. Intake of hexavalent chromium (Cr(VI)) through drinking water and food causes toxic effects, leading to serious diseases, and is a commonly reported environmental problem. Microorganisms can mitigate or prevent the toxic effects caused by heavy metals in addition to having effective resistance mechanisms to prevent cell damage and bind to these metals, sequestering them from the cell surface and removing them from the body. Species of Lactobacillus, Streptococcus, Bacillus and Bifidobacterium present in the human mouth and gut and in fermented foods have the ability to bind and detoxify some of these substances. This review address the primary topics related to Cr(VI) poisoning in animals and humans and the use of probiotics as a way to mitigate or prevent the toxic effects caused by Cr(VI). Further advances in the genetic knowledge of such microorganisms may lead to discoveries which will clarify the most active microorganisms that act as bioprotectants in bodies exposed to Cr(VI) and are an affordable option for people and animals intoxicated by the oral route. (c) 2016 Society of Chemical Industry. PMID- 26997543 TI - Drug harms and drug policies in Sub-Saharan Africa: Implementation science and HIV epidemics. PMID- 26997542 TI - Modeling the structure and operation of drug supply chains: The case of cocaine and heroin in Italy and Slovenia. AB - Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible biases in how respondents describe their drug dealing activities. PMID- 26997544 TI - Needs-based public health service provision ensures equity. PMID- 26997545 TI - In situ Fabrication of alpha-Bi2O3/(BiO)2CO3 Nanoplate Heterojunctions with Tunable Optical Property and Photocatalytic Activity. AB - Exploring the full potential use of heterojunction photocatalysts containing bismuth has attracted considerable interest in recent years. Fabrication of well defined heterojunction photocatalysts with precise modulation of their chemical composition is crucial for tuning their optical properties and photocatalytic activity. In this study, we fabricated nanoplate alpha-Bi2O3/(BiO)2CO3 heterojunctions through in situ thermal treatment of (BiO)2CO3 nanoplates synthesized using a facile hydrothermal process. Characterization results showed that the as-prepared Bi2O3/(BiO)2CO3 heterojunctions possessed distinct crystal interface and exhibited pronounced structural and optical modulation, resulting in significant improvement of their photocatalytic activity for NO removal under simulated solar light irradiation compared with pristine (BiO)2CO3. Electron spin resonance spectroscopy showed that ?OH radicals were the major reactive species involved in NO degradation, which is consistent with the theoretical analysis. The heterojunction formation can not only broaden the light absorption range but also improve the charge separation of photo-induced electron-hole pairs. This study is an important advancement in the development of semiconductor heterojunctions towards achieving functional photocatalysts. PMID- 26997546 TI - Prostaglandin E2 inhibits collagen synthesis in dermal fibroblasts and prevents hypertrophic scar formation in vivo. AB - Hypertrophic scarring is a common dermal fibroproliferative disorder characterized by excessive collagen deposition. Prostaglandin E2 (PGE2 ), an important inflammatory product synthesized via the arachidonic acid cascade, has been shown to act as a fibroblast modulator and to possess antifibroblastic activity. However, the mechanism underlying the antifibrotic effect of PGE2 remains unclear. In this study, we explored the effects of PGE2 on TGF-beta1 treated dermal fibroblasts in terms of collagen production and to determine the regulatory pathways involved, as well as understand the antiscarring function of PGE2 in vivo. We found that PGE2 inhibited TGF-beta1-induced collagen synthesis by regulating the balance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP). It did so by upregulating cAMP through the E prostanoid (EP)2 receptor. We determined that inhibition of the TGF-beta1/Smad pathway by PGE2 is associated with its ability to inhibit collagen synthesis. An in vivo study further confirmed that PGE2 inhibits hypertrophic scar formation by decreasing collagen production. Our results demonstrate that the novel anti scarring function of PGE2 is achieved by balancing MMPs/TIMP expression and decreasing collagen production. PMID- 26997547 TI - Understanding hematopoiesis from a single-cell standpoint. AB - The cellular diversity of the hematopoietic system has been extensively studied, and a plethora of cell surface markers have been used to discriminate and prospectively purify different blood cell types. However, even within phenotypically identical fractions of hematopoietic stem and progenitor cells or lineage-restricted progenitors, significant functional heterogeneity is observed when single cells are analyzed. To address these challenges, researchers are now using techniques to follow single cells and their progeny to improve our understanding of the underlying functional heterogeneity. On November 19, 2015, Dr. David Kent and Dr. Leila Perie, two emerging young group leaders, presented their recent efforts to dissect the functional properties of individual cells with a webinar series organized by the International Society for Experimental Hematology. Here, we provide a summary of the presented methods for cell labeling and clonal tracking and discuss how these different techniques have been employed to study hematopoiesis. PMID- 26997549 TI - Palaeomagnetism of the Upper Miocene- Lower Pliocene lavas from the East Carpathians: contribution to the paleosecular variation of geomagnetic field. AB - Investigations of the paleosecular variation of the geomagnetic field on geological timescales depend on globally distributed data sets from lava flows. We report new paleomagnetic results from lava flows of the East Carpathian Mountains (23.6 degrees E, 46.4 degrees N) erupted between 4 and 6 Ma. The average virtual geomagnetic pole position (76 sites) includes the North Geographic Pole and the dispersion of virtual geomagnetic poles is in general agreement with the data of the Time Averaged geomagnetic Field Initiative. Based on this study and previous results from the East Carpathians obtained from 0.04-4 Ma old lava flows, we show that high value of dispersion are characteristic only for 1.5-2.8 Ma old lava flows. High values of dispersion during the Matuyama chron are also reported around 50 degrees N, in the global paleosecular variation data set. More data are needed at a global level to determine if these high dispersions reflect the behaviour of the geomagnetic field or an artefact of inadequate number of sites. This study of the East Carpathians volcanic rocks brings new data from southeastern Europe and which can contribute to the databases for time averaged field and paleosecular variation from lavas in the last 6 Ma. PMID- 26997548 TI - Discovery of a new Wolbachia supergroup in cave spider species and the lateral transfer of phage WO among distant hosts. AB - Wolbachia are widespread intracellular bacteria infecting the major classes of arthropods and some filarial nematodes. In arthropods, Wolbachia have evolved various intriguing reproductive manipulations, including cytoplasmic incompatibility, parthenogenesis, feminization, and male killing. Sixteen supergroups of Wolbachia have been identified, named A-Q (except G). Though Wolbachia present great diversity in arthropods, spiders, especially cave spiders, are still a poorly surveyed group of Wolbachia hosts. Here, we report a novel Wolbachia supergroup from nine Telema cave spiders (Araneae: Telemidae) based on five molecular markers (16S rRNA, ftsZ, gltA, groEL, and coxA). In addition, phage WO, which was previously reported only in Wolbachia supergroups A, B, and F, infects this new Wolbachia supergroup. We detected a 100% infection rate for phage WO and Wolbachia in Telema species. The phylogenetic trees of phage WO and Wolbachia are not congruent, which suggests that horizontal transfer of phage WO has occurred in these secluded species. Additionally, these data indicate Telema-Wolbachia-phage WO may be a good model for exploring the horizontal transfer history of WO among different host species. PMID- 26997550 TI - Preparing Future Registered Dietitian Nutritionists for Working with Populations with Food Insecurity: A New Food Insecurity/Food Banking Supervised Practice Concentration Piloted with Dietetic Interns. PMID- 26997551 TI - Immunostimulant activities of the aqueous methanolic extract of Leptadenia pyrotechnica, a plant from Cholistan desert. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Leptadenia pyrotechnica (Forssk.) Decne (Asclepiadaceae) is a well-renowned medicinal shrub, used by herbal practitioners for various ailments including allergic rhinitis, productive cough, abortion, diabetes, stomach disorders, fever, kidney disorders, stones and cancer AIM OF THE STUDY: On the basis of folkloric uses, L. pyrotechnica was selected from the wide medicinal flora of the Cholistan desert of Pakistan, for the exploration of immunomodulatory potential. MATERIALS AND METHODS: Aqueous methanolic (30:70) extract of aerial parts of L. pyrotechnica (Lp. Cr) was prepared by 3 days thrice maceration and subsequent evaporation under reduced pressure. In-vivo experiments were performed in Wistar albino rats including neutrophil adhesion test, haemagglutinating antibody (HA) titre, delayed-type hypersensitivity response, phagocytic activity and cyclophosphamide-induced myelosuppression. RESULTS: Lp. Cr produced a significant increase in phagocytic index in dose-dependent fashion (3.56, 4.18 and 5.42 at 30, 100 and 300mg/kg, respectively) as well as an augmented response in the delayed-type hypersensitivity reaction and HA titre induced by sheep erythrocytes. Lp. Cr also showed improved adhesion of neutrophils with nylon pellets (15.28, 27.85 and 38.42% at the doses of 30, 100 and 300mg/kg) and prevented myelosuppression in cyclophosphamide-treated rats as evidenced from the hematological parameters. The results of treatment were compared with normal and standard control groups throughout the study and the effects by Lp. Cr (300mg/kg) were found to be comparable with Levamisole. CONCLUSIONS: The results indicated that L. pyrotechnica possesses immunostimulatory activity and justify its traditional use for the control and management of diseases in which the immune system needs to be stimulated like infectious diseases. PMID- 26997552 TI - Increased involvement of Panax notoginseng in the mechanism of decreased hepatotoxicity induced by Tripterygium wilfordii in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The key problem with toxic Chinese herbs in clinical applications is how to find the most effective method to reduce toxicity. This study focuses on discussing the mechanism of decreased hepatotoxicity by the usage compatibility of two commonly used traditional Chinese drugs that are used clinically: Tripterygium wilfordii Hook. f. (TW) and Panax notoginseng (Burkill) F.H. Chen (PN). Additionally, based on the results from using metabonomics technology, the usage compatibility with these two herbs that was originated from clinical experience is the first to clarify the rationality of the drug combination. MATERIALS AND METHODS: Through a fast and effective HPLC method, plasma concentration-time profiles and triptolide distribution characteristics in liver, heart, spleen, lung and kidney tissues were simultaneously determined in rats after oral administration of the aqueous extract of TW and TW-PN. The reduced hepatotoxicity data of the usage compatibility with TW and PN were also investigated, and then a UHPLC-QTOF/MS method was developed and validated for the explanation of the reduced hepatotoxicity mechanism. RESULTS: It was indicated that nine endogenous metabolites might be potential biomarkers for hepatotoxicity induced by TW. In addition, the plasma concentration-time profiles and the distribution characteristics of TP in rats were changed after oral administration of the aqueous extract of TW-PN, and simultaneously, the hepatotoxicity was obviously decreased. CONCLUSIONS: The results indicated that usage compatibility with TW and PN was reasonable in clinical use. To the best of our knowledge, this is the first report to describe the mechanism of reducing hepatotoxicity with the combined use of TW and PN from clinical experience. PMID- 26997553 TI - Ethnobotanical approaches of traditional medicine studies in Southwest China: A literature review. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The ethnopharmacology of Southwest China is extremely interesting because of the region's high level of cultural and medicinal plant diversity. Little work has been done to document the traditional medicinal practices in this area. This review aims to provide an overview of the current knowledge of how medicinal plants in this area are utilized, and conserved, in order to better understand the medicinal flora, identify research gaps, and suggest directions for further research. MATERIAL AND METHODS: A literature review was conducted that included peer reviewed journals, website, books, theses and scientific reports from 1979 to 2014. The distribution and characteristics of medicinal plant knowledge in each province, methods applied in research, and the fluctuations of literature in 5 year intervals were analyzed. The distribution research on different plant groups including fungi, ferns, mosses, and vascular plants were also analyzed. RESULTS AND DISCUSSION: A total of 436 publications from 1979 to 2014 were selected for analysis. References were classified into three stages: discovery stage, utilization stage and conservation stage. Detailed results about the focus of the references, the methods applied, the development and relationship among all folk medicine in Southwest China, Daodi ethnomedicinal resources, Pharmacological studies and Toxicology studies were discussed. While, compared to the rich medicinal flora, the complex demographics and cultural diversity, a large gap still exist to fully understand and document the medicinal flora. CONCLUSIONS: Based on the review results, most research efforts in Southwest China focused on the first step: discovery of traditional usage, geographical distribution, and taxonomy of medicinal species. Only a small percentage of traditional uses or treatments have been tested by modern ethnobotanical approaches. Further research needs to put more emphasis on identifying adulterations, evaluating of Daodi medicine, and elucidating effective compounds from traditional drugs, using molecular and phytochemical approaches. Knowledge on ethnic and cultural aspects of medicinal plant species, to develop effective conservation and sustainable use protocols is lacking. PMID- 26997554 TI - Healthcare and happiness in the Kingdom of Bhutan. PMID- 26997555 TI - Aflatoxin B1 impairs mitochondrial functions, activates ROS generation, induces apoptosis and involves Nrf2 signal pathway in primary broiler hepatocytes. AB - Aflatoxin B1 (AFB1) is known as a mycotoxin that causes various health problems in animals, but the precise mechanism of AFB1 on mitochondrial functions and apoptosis in primary broiler hepatocytes (PBHs) is not clear. The objective of this study was to investigate the effects of AFB1 on the mitochondrial functions, reactive oxygen species (ROS) generation, apoptosis and nuclear factor erythroid 2-like factor 2 (Nrf2)-related signal pathway in PBHs. Here, the mitochondrial membrane potential (MMP), ROS generation, antioxidative genes and apoptosis in PBHs induced by AFB1 were investigated. The results showed that AFB1 evoked mitochondrial ROS generation, decreased MMP and induced apoptosis in PBHs. AFB1 increased the percentage of apoptotic cells, and expression of caspase-9 and caspase-3, upregulated messenger RNA (mRNA) expression of Nrf2 and downregulated mRNA expressions of NAD(P)H: quinine oxidoreductase 1, superoxide dismutase and Heme oxygenase 1 in PBHs. The expression of Bax was also observed in cytoplasm. These findings suggested AFB1 results in a significant impairment of mitochondrial functions, activates ROS generation, induces apoptosis, and is involved in Nrf2 signal pathway through mitochondria ROS-dependent signal pathways in PBHs. PMID- 26997556 TI - TCR-engineered T cells to treat tumors: Seeing but not touching? AB - Adoptive transfer of T cells gene-engineered with T cell receptors (TCRs) has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to accurately select TCRs that demonstrate antigen-selective responses that are restricted to tumor cells and, at the same time, include strategies that restore or enhance the entry, migration and local accumulation of T cells in tumor tissues. Here, we present the current standing of TCR-engineered T cell therapy, discuss and propose procedures to select TCRs as well as strategies to sensitize the tumor to T cell trafficking, and provide a rationale for combination therapies with TCR-engineered T cells. PMID- 26997558 TI - Does paracetamol still have a future in osteoarthritis? PMID- 26997557 TI - RETRACTED: Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. AB - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of osteoarthritis pain management. We aimed to assess the effectiveness of different preparations and doses of NSAIDs on osteoarthritis pain in a network meta analysis. METHODS: For this network meta-analysis, we considered randomised trials comparing any of the following interventions: NSAIDs, paracetamol, or placebo, for the treatment of osteoarthritis pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the reference lists of relevant articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at least 100 patients per group. The prespecified primary and secondary outcomes were pain and physical function, and were extracted in duplicate for up to seven timepoints after the start of treatment. We used an extension of multivariable Bayesian random effects models for mixed multiple treatment comparisons with a random effect at the level of trials. For the primary analysis, a random walk of first order was used to account for multiple follow-up outcome data within a trial. Preparations that used different total daily dose were considered separately in the analysis. To assess a potential dose-response relation, we used preparation-specific covariates assuming linearity on log relative dose. FINDINGS: We identified 8973 manuscripts from our search, of which 74 randomised trials with a total of 58,556 patients were included in this analysis. 23 nodes concerning seven different NSAIDs or paracetamol with specific daily dose of administration or placebo were considered. All preparations, irrespective of dose, improved point estimates of pain symptoms when compared with placebo. For six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90 mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the difference to placebo is at or below a prespecified minimum clinically important effect for pain reduction (effect size [ES] -0.37) was at least 95%. Among maximally approved daily doses, diclofenac 150 mg/day (ES -0.57, 95% credibility interval [CrI] -0.69 to -0.46) and etoricoxib 60 mg/day (ES -0.58, 0.73 to -0.43) had the highest probability to be the best intervention, both with 100% probability to reach the minimum clinically important difference. Treatment effects increased as drug dose increased, but corresponding tests for a linear dose effect were significant only for celecoxib (p=0.030), diclofenac (p=0.031), and naproxen (p=0.026). We found no evidence that treatment effects varied over the duration of treatment. Model fit was good, and between-trial heterogeneity and inconsistency were low in all analyses. All trials were deemed to have a low risk of bias for blinding of patients. Effect estimates did not change in sensitivity analyses with two additional statistical models and accounting for methodological quality criteria in meta-regression analysis. INTERPRETATION: On the basis of the available data, we see no role for single-agent paracetamol for the treatment of patients with osteoarthritis irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the most effective NSAID available at present, in terms of improving both pain and function. Nevertheless, in view of the safety profile of these drugs, physicians need to consider our results together with all known safety information when selecting the preparation and dose for individual patients. FUNDING: Swiss National Science Foundation (grant number 405340-104762) and Arco Foundation, Switzerland. PMID- 26997559 TI - In situ monitoring of vapour-induced assembly of pharmaceutical cocrystals using a benchtop powder X-ray diffractometer. AB - We describe a simple setup for in situ continuous monitoring of vapour-induced transformations of organic solids using a benchtop powder X-ray diffractometer. Proof-of-principle application of this setup to model pharmaceutical cocrystals reveals complex reactivity, transformations of reaction intermediates within minutes, and a simple route to the rarely observed monoclinic form of the pharmaceutical cocrystal of carbamazepine and saccharin. PMID- 26997560 TI - Modelling the role of CtfA/B in reverse shift continuous culture experiments of Clostridium acetobutylicum. AB - In continuous phosphate-limited conditions, under pH control from high pH (pH ? 5.2) to low pH (pH ? 5.2), the metabolism of the Gram-positive bacterium Clostridium acetobutylicum,switches from acid to solvent production. Three main enzymes are responsible for the shift, acetoacetate decarboxylase (Adc), alcohol dehydrogenase (AdhE1/2) and a CoA-transferase (CtfA/B), which are produced in increased quantities during solventogenesis. A two-population model, Millat et al. (2013) and fitted to such 'forward'-shift data, can explain this, as well as observed changes in optical density immediately following the shift: an acidogenic subpopulation is washed out and a solventogenic subpopulation grows in its place, each with distinct physiologies and proteomes. We fit this model to a 'reverse'-shift experiment, where the pH is increased from solventogenic to acidogenic conditions. We find corresponding changes in reaction rates, with AdhE1 and Adc production falling, as in the 'forward' experiments; however, for CtfA/B, the best fit surprisingly arises from the same level of production in both conditions. We propose experiments that would test whether this is a model artefact or accurately reflects cultures shifted in this reverse direction, and, if true, may suggest that over-expressing CtfA/B in both solventogenic and acidogenic conditions could improve the efficiency of fermentation. PMID- 26997561 TI - Zeolitic imidazolate framework-methacrylate composite monolith characterization by inverse gas chromatography. AB - Thermodynamic characterization of butyl methacrylate-co-ethylene dimethacrylate neat monolith and zeolitic imidazolate framework-8 incorporated with butyl methacrylate-co-ethylene dimethacrylate composite monolith were studied using inverse gas chromatography at infinite dilution under 1MPa column pressure and various column temperatures. The free energy of adsorption (DeltaGA), enthalpy of adsorption (DeltaHA) and entropy of adsorption (DeltaSA) were determined using a series of n-alkanes. The dispersive component of surface energy (gammaS(D)) was estimated by Dorris-Gray and Schultz et al. METHODS: The composite monolith showed a more energetic surface than the neat monolith. The acidic, KA, and basic, KD, parameters for both materials were estimated using a group of polar probes. A basic character was concluded with more basic behavior for the neat monolith. Flory-Huggins parameter, chi, was taken as a measure of miscibility between the probes with the low molecular weight and the high molecular weight monolith. Inverse gas chromatography provides a better understanding of the role of incorporated zeolitic imidazolate framework (ZIF-8) into the polymer matrix in its monolithic form. PMID- 26997562 TI - Influence of fibrous encapsulation on electro-chemical properties of TiN electrodes. AB - The aim of this study was to investigate how the electrochemical properties of porous titanium nitride stimulation electrode are affected by fibrous encapsulation in vivo. Electrochemical impedance spectroscopy (EIS), cyclic voltammetry and voltage transient (VT) measurements were performed in vivo and in phosphate buffered saline, where the encapsulation process is absent. EIS was used as a non-invasive measurement to follow the inflammation, healing and encapsulation process. EIS showed that the healing and encapsulation process lasted 3-4 weeks. The VTs increased during the first 3-4 weeks, after which they stabilized. The charge storage capacity (CSC) decreased most during the first 3-4 weeks. The increasing VTs and decreasing CSC during the first 3-4 weeks after implantation of the in vivo electrodes seem related to healing and fibrous encapsulation. It is suggested that the charge injection pathway during the encapsulation process changes, which implies that charge injection limits are underestimated with conventional methods. PMID- 26997563 TI - Non-invasive estimation of static and pulsatile intracranial pressure from transcranial acoustic signals. AB - The aim of the present study was to examine whether a method for estimation of non-invasive ICP (nICP) from transcranial acoustic (TCA) signals mixed with head generated sounds estimate the static and pulsatile invasive ICP (iICP). For that purpose, simultaneous iICP and mixed TCA signals were obtained from patients undergoing continuous iICP monitoring as part of clinical management. The ear probe placed in the right outer ear channel sent a TCA signal with fixed frequency (621 Hz) that was picked up by the left ear probe along with acoustic signals generated by the intracranial compartment. Based on a mathematical model of the association between mixed TCA and iICP, the static and pulsatile nICP values were determined. Total 39 patients were included in the study; the total number of observations for prediction of static and pulsatile iICP were 5789 and 6791, respectively. The results demonstrated a good agreement between iICP/nICP observations, with mean difference of 0.39 mmHg and 0.53 mmHg for static and pulsatile ICP, respectively. In summary, in this cohort of patients, mixed TCA signals estimated the static and pulsatile iICP with rather good accuracy. Further studies are required to validate whether mixed TCA signals may become useful for measurement of nICP. PMID- 26997564 TI - Dermis mechanical behaviour after different cell removal treatments. AB - Human acellular dermal matrices (HADMs) are used in reconstructive surgery as scaffolds promoting autologous tissue regeneration. Critical to the HADM ability to remodel and integrate into the host tissue is the removal of cells while maintaining an intact extracellular architecture. The objective of this work is to develop a methodology to analyse the mechanical properties of HADMs after decellularization to identify its ideal form of treatment and its duration. Two different decellularization techniques were used as a benchmark: the first is a well-established technique (incubation in NaOH for 1-7 weeks), and the second is an innovative technique developed by this research group (incubation in DMEM (Dulbecco's modified Eagle medium) for 1-7 weeks). After decellularization, the specimens underwent uniaxial tensile tests, and experimental data were represented with stress strain curves, calculating both engineering and true values. Mechanical tests have led to the identification of the optimal method (NaOH or DMEM) and duration for the decellularization treatment; differences between engineering and true values can reach 84%, but the engineering values remain useful to make comparisons, providing reliable indications with a simpler experimental set up and data processing. PMID- 26997565 TI - Corrigendum: Localised excitation of a single photon source by a nanowaveguide. PMID- 26997566 TI - Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients. AB - AIM: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. METHODS: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L T4, 25 and 50 mcg/d for patients with TSH<=10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. RESULTS: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11 dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11 dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. CONCLUSION: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels. PMID- 26997569 TI - A cheek tumour. PMID- 26997567 TI - Advances in development of fluorescent probes for detecting amyloid-beta aggregates. AB - With accumulating evidence suggesting that amyloid-beta (Abeta) deposition is a good diagnostic biomarker for Alzheimer's disease (AD), the discovery of active Abeta probes has become an active area of research. Among the existing imaging methods, optical imaging targeting Abeta aggregates (fibrils or oligomers), especially using near-infrared (NIR) fluorescent probes, is increasingly recognized as a promising approach for the early diagnosis of AD due to its real time detection, low cost, lack of radioactive exposure and high-resolution. In the past decade, a variety of fluorescent probes have been developed and tested for efficiency in vitro, and several probes have shown efficacy in AD transgenic mice. This review classifies these representative probes based on their chemical structures and functional modes (dominant solvent-dependent mode and a novel solvent-independent mode). Moreover, the pharmaceutical characteristics of these representative probes are summarized and discussed. This review provides important perspectives for the future development of novel NIR Abeta diagnostic probes. PMID- 26997571 TI - Rhabdoid Glioblastoma: Touch Imprint Cytology Clearly Demonstrates Globular Cytoplasmic Inclusions. PMID- 26997568 TI - Carbocisteine attenuates TNF-alpha-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-kappaB and ERK1/2 MAPK signaling pathways. AB - AIM: We previously proven that carbocisteine, a conventional mucolytic drug, remarkably reduced the rate of acute exacerbations and improved the quality of life in the patients with chronic obstructive pulmonary disease. In this study we investigated the mechanisms underlying the anti-inflammatory effects of carbocisteine in human alveolar epithelial cells in vitro. METHODS: Human lung adenocarcinoma cell line A549 was treated with TNF-alpha (10 ng/mL). Carbocisteine was administered either 24 h prior to or after TNF-alpha exposure. The cytokine release and expression were measured using ELISA and qRT-PCR. Activation of NF-kappaB was analyzed with Western blotting, immunofluorescence assay and luciferase reporter gene assay. The expression of ERK1/2 MAPK signaling proteins was assessed with Western blotting. RESULTS: Carbocisteine (10, 100, 1000 MUmol/L), administered either before or after TNF-alpha exposure, dose dependently suppressed TNF-alpha-induced inflammation in A549 cells, as evidenced by diminished release of IL-6 and IL-8, and diminished mRNA expression of IL-6, IL-8, TNF-alpha, MCP-1 and MIP-1beta. Furthermore, pretreatment with carbocisteine significantly decreased TNF-alpha-induced phosphorylation of NF kappaB p65 and ERK1/2 MAPK, and inhibited the nuclear translocation of p65 subunit in A549 cells. In an NF-kappaB luciferase reporter system, pretreatment with carbocisteine dose-dependently inhibited TNF-alpha-induced transcriptional activity of NF-kappaB. CONCLUSION: Carbocisteine effectively suppresses TNF-alpha induced inflammation in A549 cells via suppressing NF-kappaB and ERK1/2 MAPK signaling pathways. PMID- 26997570 TI - Butterfly-cartilage tympanoplasty in children: A 28-case series and literature review. AB - OBJECTIVE: This study presents results for a pediatric series of tympanoplasty using the butterfly-cartilage technique, with comparison to literature reports. METHODS: A retrospective study included patients aged between 2 and 12 years receiving tympanoplasty performed by a single senior surgeon in our department between 2003 and 2012, for whom pre- and postoperative tympanum imaging was complete. Results were analyzed at a minimum 10 months' follow-up in terms of graft healing and auditory data, with pre- and postoperative audiograms and calculation of mean hearing loss. RESULTS: Twenty-eight tympanoplasties were performed in 27 children: 16 males, 11 females; in 1 case, perforation was bilateral. Perforation location was inferior or antero-inferior in 14 cases (50%), antero-superior in 9 (32.1%) and anterior in 5 (17.9%). Perforation size on otoscopy ranged from 11.1% to 36.4% of tympanum area (mean, 26.3%). Mean follow-up was 25 months. Closure of the perforation was achieved in 87.7% of cases. Mean hearing loss was 20.2dB (range, 10-31.25dB) preoperatively and 14dB (range, 5-31.25dB) postoperatively. DISCUSSION: We analyze our results and compare them with the international literature to refine indications for this technique of tympanic repair. CONCLUSION: Tympanoplasty using the butterfly cartilage technique was reliable and easy to perform. It should be included in the therapeutic armamentarium for moderate non-marginal tympanic perforation. In the present series, the technique was reserved to perforations involving less than 40% of tympanum area. PMID- 26997572 TI - A Redox-Active Binder for Electrochemical Capacitor Electrodes. AB - A promising strategy for increasing the performance of supercapacitors is proposed. Until now, a popular strategy for increasing the specific capacity of the electrode consists of grafting redox molecules onto a high surface area carbon structure to add a faradaic contribution to the charge storage. Unfortunately, the grafting of molecules to the carbon surface leads to a dramatic decrease of the electrochemical performances of the composite material. Herein, we used the organic binder as an active material in the charge/discharge process. Redox molecules were attached onto its polymeric skeleton to obtain a redox binder with the dual functionalities of both the binder and the active material. In this way, the electrochemical performance was improved without detrimentally affecting the properties of the porous carbon. Results showed that the use of a redox binder is promising for enhancing both energy and power densities. PMID- 26997573 TI - Unusual coexisting thyroglossal duct cyst and second branchial cleft fistula in an adult. PMID- 26997574 TI - Feeding methods for children with cleft lip and/or palate: a systematic review. AB - INTRODUCTION: Feeding difficulties in children with cleft lip and palate (CLP) are frequent and appear at birth due to impairment of sucking and swallowing functions. The use of appropriate feeding methods for the different types of cleft and the period of the child's life is of utmost importance for their full development. OBJECTIVE: Review studies comparing feeding methods for children with CLP, pre- and postoperatively. METHODS: The search covered the period between January 1990 and August 2015 in the PubMed, LILACS, SciELO, and Google Scholar databases using the terms: cleft lip or cleft palate and feeding methods or breastfeeding or swallowing disorders and their synonyms. This systematic review was recorded in PROSPERO under number CRD42014015011. Publications that compared feeding methods and published in Portuguese, English, and Spanish were included in the review. Studies with associated syndromes, orthopedic methods, or comparing surgical techniques were not included. RESULTS: The three reviewed studies on the period prior to surgical repair showed better feeding performance with three different methods: squeezable bottle, syringe, and paladai bottle. Only one study addressed the postoperative period of cleft lip and/or palate repair, with positive results for the feeding method with suction. Likewise, the post-lip repair studies showed better results with suction methods. After palatoplasty, two studies showed better performance with alternative feeding routes, one study with suction method, and one study that compared methods with no suction showed better results with spoon. CONCLUSION: The studies show that prior to surgical repair, the use of alternative methods can be beneficial. In the postoperative period following lip repair, methods with suction are more beneficial. However, in the postoperative period of palatoplasty, there are divergences of opinion regarding the most appropriate feeding methods. PMID- 26997575 TI - The relationship between senile hearing loss and vestibular activity. AB - INTRODUCTION: A considerable high number of SNHL patients also suffer from dizziness and related vestibular symptoms. OBJECTIVE: To evaluate the association of vestibular dysfunction and sensorineural hearing loss (SNHL) in adult patients. METHODS: Prospective, double-blinded, controlled studies composed by 63 adult patients without any vestibular symptoms or diagnosed vestibular diseases. Audiological status was measured with pure tone audiometry and the vestibular system was tested with vestibular evoked myogenic potential (VEMP). Patients were divided into two groups: a study group (patients with SNHL) and a control group (patients without SNHL). VEMP results of the groups were calculated and compared. RESULTS: Mean P1 (23.54) and N1 (30.70) latencies were prolonged in the study group (p<0.001) and the amplitudes of the study group were significantly reduced (p<0.001). Both parameters of the VEMP test were abnormal in the study group when compared to the control group. CONCLUSIONS: These findings suggest that age related SNHL may be accompanied by vestibular weakness without any possible predisposing factors for vestibulopathy. PMID- 26997576 TI - Effect of Uncontrolled Diabetes on Outcomes After Cystectomy in Patients With Bladder Cancer: A Population-Based Study. AB - BACKGROUND: We evaluated the complications, mortality, hospital length of stay (LOS), and cost for patients with diabetes undergoing radical cystectomy (RC). MATERIALS AND METHODS: Data were extracted from the National (Nationwide) Inpatient Sample for 2001 to 2012 using the "International Classification of Diseases, Ninth Revision, Clinical Modification" codes for patients with uncontrolled diabetes (UD) (patients with diabetes receiving treatment that did not keep the blood glucose at acceptable levels) and controlled diabetes (CD) (patients with diabetes not otherwise stated as uncontrolled) who had undergone RC. chi2 and Wilcoxon rank sum tests and multivariable regression analysis were used for statistics. The LOS and cost are presented as the median and interquartile range. RESULTS: In the present study, 989 patients had UD, 15,693 CD, and 73,603 had no diabetes (ND). Postoperative complications were significantly more common in the UD group (73%) than in the CD (51%) and ND (52%) groups (P < .0001). On multivariable analysis, the UD group were more likely than the CD group to have any complication (odds ratio [OR], 2.3; 95% confidence interval [CI], 2.0-2.7), including renal (OR, 2.1; 95% CI, 1.8-2.4) and infectious (OR, 2.7; 95% CI, 2.3-3.1) complications. Patients with UD were also 4.3 times (95% CI, 3.1-5.8) more likely to die after surgery than were patients with CD. The ND group was slightly more likely than the CD group to experience any complication (OR, 1.13; 95% CI, 1.09-1.17) and death (OR, 1.6; 95% CI, 1.4 1.8). The LOS and cost for UD patients were greater than for CD patients. On multivariable analysis, UD patients had a 30% increase in LOS and 23% increase in cost (P < .0001). CONCLUSION: The findings from the present study have demonstrated an increase in post-RC complications rates, hospital mortality, and hospital resource usage for patients with UD undergoing RC. UD might be a modifiable preoperative risk factor for post-RC morbidity and mortality. Further studies are needed to validate this association. PMID- 26997577 TI - Management of Stage IIIA (N2) Non-Small Cell Lung Cancer: A Transatlantic Perspective. PMID- 26997578 TI - Global risk of Zika virus depends critically on vector status of Aedes albopictus. PMID- 26997579 TI - APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy. AB - AIM: APF530, extended-release granisetron, provides sustained release for >=5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline recommended three-drug regimen. METHODS: HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). RESULTS: A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. CONCLUSION: APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494. PMID- 26997580 TI - Phosphodiesterase-4 inhibition as a therapeutic strategy for metabolic disorders. AB - Phosphodiesterase-4 (PDE4) hydrolyses cyclic adenosine monophosphate (cAMP), a crucial secondary messenger for cellular adaptation to diverse external stimuli. The activity of PDE4 is tightly controlled by post-translational regulation, structure-based auto-regulation and locus specific 'compartmentalization' of PDE4 with its interactive proteins (signalsomes). Through these mechanisms, PDE4 regulates cAMP levels and shapes the cAMP signalling, directing signals from the diverse external stimuli to distinct microenvironments exquisitely. Derangement of the PDE4-cAMP signalling represents a pathophysiologically relevant pathway in metabolic disorders as demonstrated through a critical role in the processes including inflammation, disordered glucose and lipid metabolism, hepatic steatosis, abnormal lipolysis, suppressed thermogenic function and deranged neuroendocrine functions. A limited number of PDE4 inhibitors are currently undergoing clinical evaluation for treating disorders such as type 2 diabetes and non-alcoholic steatohepatitis. The discovery of novel PDE4 allosteric inhibitors and signalsome-based strategies targeting individual PDE4 variants may allow PDE4 isoform selective inhibition, which may offer safer strategies for chronic treatment of metabolic disorders. PMID- 26997581 TI - CrossTalk opposing view: Intramyocellular ceramide accumulation does not modulate insulin resistance. PMID- 26997582 TI - Treatment outcomes and validation of the stopping rule for response to peginterferon in chronic hepatitis B: A Thai nationwide cohort study. AB - BACKGROUND AND AIMS: Peginterferon has demonstrated effectiveness in clinical trials in patients with chronic hepatitis B (CHB). However, its efficacy in real life settings remains unclear. We investigated the efficacy of peginterferon for CHB and validated the performance of previously identified response predictors in clinical practice. METHODS: We analyzed prospectively collected data from a Thai nationwide cohort of CHB patients treated with peginterferon alfa-2a (180 ug/week, 48 weeks). RESULTS: Among a total of 233 patients, mostly with genotype B or C, sustained response was observed in 23% of 135 hepatitis B e antigen (HBeAg)-positive patients (HBeAg seroconversion with hepatitis B virus [HBV] DNA < 2000 IU/mL) and 42% of 98 HBeAg-negative patients (HBV DNA < 2000 IU/mL with aminotransferase normalization) at 24 weeks after treatment. Age, sex, presence of cirrhosis, genotype, and pretreatment levels of aminotransferase, HBV DNA, and hepatitis B surface antigen (HBsAg) were not identified as significant predictors of sustained response. In HBeAg-positive patients, HBsAg > 20 000 IU/mL at week 12 provided a good stopping rule, with a negative predictive value of 96%. In HBeAg-negative patients, the performance of 12-week stopping rules of no decline in HBsAg with a < 2log10 decline in HBV DNA and a < 10% log10 decline in HBsAg showed modest negative predictive values of 80% and 66%, respectively, for achieving sustained response. CONCLUSION: Outcomes in CHB patients treated with peginterferon in a clinical setting are similar to those demonstrated in clinical trials. Application of the early stopping rule based on HBsAg quantification may allow individualization of therapy, particularly in HBeAg-positive patients. PMID- 26997583 TI - Association between prediabetes and risk of chronic kidney disease: a systematic review and meta-analysis. AB - AIMS: To assess the effect of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) on the incidence of chronic kidney disease. METHODS: PubMed and EMBASE were searched (for studies published up to March 2015). Effects estimated from cohort studies reporting the relationship of prediabetes to incident chronic kidney disease [kidney damage (microalbuminuria, albuminuria or proteinuria) and/or decreased glomerular filtration rate] were pooled using a random-effects model meta-analysis. RESULTS: Nine cohort studies with a total of 185 452, mainly Asian and white, participants were followed for a total of 835 146 person-years. In eight cohort studies defining impaired fasting glucose as fasting glucose 6.1-6.9 mmol/l, the summary relative risk of chronic kidney disease after adjustment for established risk factors was 1.11 (95% CI 1.02 1.21). When a study defining impaired fasting glucose as fasting glucose 5.6-6.9 mmol/dl was added, the overall relative risk of chronic kidney disease was 1.12 (95% CI 1.02-1.21). Exclusion of the only study with information on impaired glucose tolerance did not change the relative risk (1.12; 95% CI 1.02-1.21). There was no evidence of publication bias (P value for Egger test = 0.12). CONCLUSION: Prediabetes is modestly associated with an increase in chronic kidney disease risk, but this remains to be robustly confirmed. Chronic kidney disease screening among people with prediabetes, and aggressive management of prediabetes in those with chronic kidney disease may be warranted. PMID- 26997584 TI - On the nature of bonding in binary Be2O2 and Si2O2 clusters: rhombic four-center four-electron pi and sigma bonds. AB - The structural and electronic properties and chemical bonding of binary Be2O2 and Si2O2 clusters have been studied using quantum chemical calculations at the B3LYP level. For the Be2O2 cluster, the potential energy surface is probed by unbiased structural searches and the global-minimum structure was established using the B3LYP calculations, complemented by PBE0 and single-point CCSD(T) calculations for top isomers. The perfectly planar D2h Be2O2 ((1)Ag) global minimum is well defined, being at least 3.64 eV lower in energy than alternative structures at the CCSD(T)//B3LYP/aug-cc-pVTZ level. Chemical bonding analyses show that D2h Be2O2 and Si2O2 clusters possess the rhombic four-center four-electron (4c-4e) pi bond, that is, the o-bond, a conception derived from electron-deficient boron oxide clusters lately. Furthermore, the Be2O2 and Si2O2 clusters also exhibit rhombic 4c-4e sigma bonds, both for the radial and tangential sigma frameworks (sigmar and sigmat). The sigmat framework is classified as an o-bond only formally, due to the secondary contribution from the Be/Si s component. The three fold (pi, sigmar, and sigmat) o-bonds in Be2O2 and Si2O2 are considered to resemble the three-fold aromaticity in all-metal Al4(2-) dianions. A 4c-4e o-bond makes use of four O 2p electrons, which would otherwise be two lone-pairs, for a delocalized and completely bonding orbital, as well as a residual nonbonding orbital. Three-fold o-bonds thus greatly stabilize the binary Be2O2 and Si2O2 clusters. We anticipate that the bonding concept should be applicable to additional molecular systems, including those with larger heterocyclic rings. PMID- 26997585 TI - Impact of the Fukushima accident on tritium, radiocarbon and radiocesium levels in seawater of the western North Pacific Ocean: A comparison with pre-Fukushima situation. AB - Tritium, radiocarbon and radiocesium concentrations in water column samples in coastal waters offshore Fukushima and in the western North Pacific Ocean collected in 2011-2012 during the Ka'imikai-o-Kanaloa (KoK) cruise are compared with other published results. The highest levels in surface seawater were observed for 134Cs and 137Cs in seawater samples collected offshore Fukushima (up to 1.1 Bq L-1), which represent an increase by about three orders of magnitude when compared with the pre-Fukushima concentration. Tritium levels were much lower (up to 0.15 Bq L-1), representing an increase by about a factor of 6. The impact on the radiocarbon distribution was measurable, but the observed levels were only by about 9% above the global fallout background. The 137Cs (and similarly 134Cs) inventory in the water column of the investigated western North Pacific region was (2.7 +/- 0.4) PBq, while for 3H it was only (0.3 +/- 0.2) PBq. Direct releases of highly contaminated water from the damaged Fukushima NPP, as well as dry and wet depositions of these radionuclides over the western North Pacific considerably changed their distribution patterns in seawater. Presently we can distinguish Fukushima labeled waters from global fallout background thanks to short-lived 134Cs. However, in the long-term perspective when 134Cs will decay, new distribution patterns of 3H, 14C and 137Cs in the Pacific Ocean should be established for future oceanographic and climate change studies in the Pacific Ocean. PMID- 26997586 TI - The N-terminus of VDAC: Structure, mutational analysis, and a potential role in regulating barrel shape. AB - A novel feature of the voltage-dependent anion channel (VDAC, mitochondrial porin), is the barrel, comprising an odd number of beta-strands and closed by parallel strands. Recent research has focused on the N-terminal segment, which in the available structures, resides in the lumen and is not part of the barrel. In this review, the structural data obtained from vertebrate VDAC are integrated with those from VDAC in artificial bilayers, emphasizing the array of native and tagged versions of VDAC used. The data are discussed with respect to a recent gating model (Zachariae et al. (2012) Structure 20:1-10), in which the N-terminus acts not as a gate on a stable barrel, but rather stabilizes the barrel, preventing its shift into a partially collapsed, low-conductance, closed state. Additionally, the role of the N-terminus in VDAC oligomerization, apoptosis through interactions with hexokinase and its interaction with ATP are discussed briefly. PMID- 26997587 TI - Conversion Reactions of Solids: From a Surprising Three-Step Mechanism towards Directed Product Formation. AB - Directed conversion reactions from binary to multinary compounds are discovered from the reaction of Bi2 S3 and Bi2 Se3 with NiCl2 ?6 H2 O in polyol media under basic conditions. Control of the synthesis conditions allows the preparation of NiBiSe and superconducting Ni3 Bi2 S2 and Ni3 Bi2 Se2 . The formation of Ni3 Bi2 S2 from Bi2 S3 is found from an unexpected three-step reaction path with Bi and NiBi as intermediates. In the more complex Ni/Bi/Se system, the mechanism found can be used to selectively direct the reaction between the competing ternaries and to suppress side-product formation. Contrary to solid-state reactions (500 900 degrees C) control of product formation is reached at reaction temperatures and times between 166-300 degrees C and 0.5-10 h, respectively. The formation of different phases is discussed from results of DFT calculations. PMID- 26997588 TI - Synergistic action of thermoresponsive and hygroresponsive elements elicits rapid and directional response of a bilayer actuator. AB - A bilayer actuator composed of thermoresponsive and thermo/hygroresponsive elements is developed, which undergoes fast, directional and autonomous curling with a speed of up to 0.7 m s(-1) and recovers its shape by hydration. In situ tensile testing of the thermal response of individual layers provided insights into the mechanism of actuation of thermo/hygromorphic bilayers. PMID- 26997589 TI - Functional Genomic Strategies for Elucidating Human-Virus Interactions: Will CRISPR Knockout RNAi and Haploid Cells? AB - Over the last several years a wealth of transformative human-virus interaction discoveries have been produced using loss-of-function functional genomics. These insights have greatly expanded our understanding of how human pathogenic viruses exploit our cells to replicate. Two technologies have been at the forefront of this genetic revolution, RNA interference (RNAi) and random retroviral insertional mutagenesis using haploid cell lines (haploid cell screening), with the former technology largely predominating. Now the cutting edge gene editing of the CRISPR/Cas9 system has also been harnessed for large-scale functional genomics and is poised to possibly displace these earlier methods. Here we compare and contrast these three screening approaches for elucidating host-virus interactions, outline their key strengths and weaknesses including a comparison of an arrayed multiple orthologous RNAi reagent screen to a pooled CRISPR/Cas9 human rhinovirus 14-human cell interaction screen, and recount some notable insights made possible by each. We conclude with a brief perspective on what might lie ahead for the fast evolving field of human-virus functional genomics. PMID- 26997590 TI - Alphaherpesvirus Latency: A Dynamic State of Transcription and Reactivation. AB - Alphaherpesviruses infect a variety of species from sea turtles to man and can cause significant disease in mammals including humans and livestock. These viruses are characterized by a lytic and latent state in nerve ganglia, with the ability to establish a lifelong latent infection that is interrupted by periodic reactivation. Previously, it was accepted that latency was a dominant state and that only during relatively infrequent reactivation episodes did latent genomes within ganglia become transcriptionally active. Here, we review recent data, focusing mainly on Herpes Simplex Virus type 1 which indicate that the latent state is more dynamic than recently appreciated. PMID- 26997591 TI - Nuclear Egress of Herpesviruses: The Prototypic Vesicular Nucleocytoplasmic Transport. AB - Herpesvirus particles mature in two different cellular compartments. While capsid assembly and packaging of the genomic linear double-stranded DNA occur in the nucleus, virion formation takes place in the cytoplasm by the addition of numerous tegument proteins as well as acquisition of the viral envelope by budding into cellular vesicles derived from the trans-Golgi network containing virally encoded glycoproteins. To gain access to the final maturation compartment, herpesvirus nucleocapsids have to cross a formidable barrier, the nuclear envelope (NE). Since the ca. 120 nm diameter capsids are unable to traverse via nuclear pores, herpesviruses employ a vesicular transport through both leaflets of the NE. This process involves proteins which support local dissolution of the nuclear lamina to allow access of capsids to the inner nuclear membrane (INM), drive vesicle formation from the INM and mediate inclusion of the capsid as well as scission of the capsid-containing vesicle (also designated as "primary virion"). Fusion of the vesicle membrane (i.e., the "primary envelope") with the outer nuclear membrane subsequently results in release of the nucleocapsid into the cytoplasm for continuing virion morphogenesis. While this process has long been thought to be unique for herpesviruses, a similar pathway for nuclear egress of macromolecular complexes has recently been observed in Drosophila. Thus, herpesviruses may have coopted a hitherto unrecognized cellular mechanism of vesicle-mediated nucleocytoplasmic transport. This could have far reaching consequences for our understanding of cellular functions as again unraveled by the study of viruses. PMID- 26997592 TI - Structure and Associated Biological Functions of Viroids. AB - Mature viroids consist of a noncoding, covalently closed circular RNA that is able to autonomously infect respective host plants. Thus, they must utilize proteins of the host for most biological functions such as replication, processing, transport, and pathogenesis. Therefore, viroids can be regarded as minimal parasites of the host machinery. They have to present to the host machinery the appropriate signals based on either their sequence or their structure. Here, we summarize such sequence and structural features critical for the biological functions of viroids. PMID- 26997593 TI - Hassan Farsam (1932-2016). PMID- 26997594 TI - Study of Silymarin and Vitamin E Protective Effects on Silver Nanoparticle Toxicity on Mice Liver Primary Cell Culture. AB - Nanotechnology is a most promising field for generating new applications in medicine, although, only few nano products are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nano-silver has biological properties which are significant for consumer products, food technology, textiles, and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products. The use of nano-silver is becoming more and more widespread in medicine and related applications, and due to its increasing exposure, toxicological and environmental issues need to be raised. Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and they induced intracellular oxidative stress. AgNP reduced ATP content of the cell and caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. Silymarin was known as a hepatoprotective agent that is used in the treatment of hepatic diseases including viral hepatitis, alcoholic liver diseases, Amanita mushroom poisoning, liver cirrhosis, toxic and drug-induced liver diseases. It promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation, and protects against glutathione depletion. Vitamin E is a well-known antioxidant and has hepatoprotective effect in liver diseases. In this study, we investigated the cytotoxic effects of Ag NPs on primary liver cells of mice. Cell viability (cytotoxicity) was examined with MTT assay after primary liver cells of mice exposure to AgNPs at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration- dependent decrease of cell viability (IC50 value = 121.7 ppm or ug/ml). Then the hepatoprotective effect of silymarin and vitamin E were experimented on silver nanoparticle toxicity on mice liver primary cell culture. The results showed that silymarin at 600 ug/ml and vitamin E at 2500 umol/l have protective effects on silver nanoparticle toxicity on mice liver primary cell culture. Viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles at 121.7 ppm and co-treatment of silymarin, and vitamin E is more than viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles and silymarin or silver nanoparticles and vitamin E. PMID- 26997595 TI - The Effect of Otic Melanocyte Destruction on Auditory and Vestibular Function: a Study on Vitiligo Patients. AB - The hallmark of vitiligo is the disappearance of melanocytes from the skin. As a result, of melanocytes presence in the auditory and vestibular apparatus, the involvement of these systems in vitiligo which targets the melanocytes of the whole body is possible; suggesting that vitiligo is a systemic disease rather than a purely cutaneous problem. A total of 21 patients with vitiligo were enrolled in this study. A group of 20 healthy subjects served as a control group. Pure tone audiometry (PTA), auditory brainstem responses (ABR) and vestibular evoked myogenic potentials (VEMP) were carried out in all participants. High frequency sensory neural hearing loss was seen in 8 (38.09%) patients. ABR analysis revealed 10 (47.61%) had an abnormal increase in latency of wave III, and 6 (28.57%) had an abnormal prolongation of IPL I-III, however, regarding our VEMP findings, there were no recorded responses on left ear of 1 (4.76%) patient and latency of p13 was prolonged in 5(23.80%) patients. There was no correlation between ages, duration of disease, and any of the recorded parameters (P>0.05). In the present survey, we highlighted the auditory and vestibular involvement in vitiligo patients. PMID- 26997596 TI - Estimating the Relationship between Economic Growth and Health Expenditures in ECO Countries Using Panel Cointegration Approach. AB - Increasing knowledge of people about health leads to raising the share of health expenditures in government budget continuously; although governors do not like this rise because of budget limitations. This study aimed to find the association between health expenditures and economic growth in ECO countries. We added health capital in Solow model and used the panel cointegration approach to show the importance of health expenditures in economic growth. For estimating the model, first we used Pesaran cross-sectional dependency test, after that we used Pesaran CADF unit root test, and then we used Westerlund panel cointegration test to show if there is a long-term association between variables or not. After that, we used chaw test, Breusch-Pagan test and Hausman test to find the form of the model. Finally, we used OLS estimator for panel data. Findings showed that there is a positive, strong association between health expenditures and economic growth in ECO countries. If governments increase investing in health, the total production of the country will be increased, so health expenditures are considered as an investing good. The effects of health expenditures in developing countries must be higher than those in developed countries. Such studies can help policy makers to make long-term decisions. PMID- 26997597 TI - Detection of Metallo-beta-Lactamase Producing Pseudomonas aeruginosa Isolated from Public and Private Hospitals in Baghdad, Iraq. AB - Metallo-beta-lactamase (MBL) producing Pseudomonas aeruginosa has been reported to be an important nosocomial infection. Its intrinsic and acquired resistance to various antimicrobial agents and its ability to develop multidrug resistance imposes a serious therapeutic problem. Different clinical samples were collected from public and private hospitals in Baghdad city, Iraq. Bacterial identification was done using conventional cultural, biochemical tests, and VITEk 2 system. Minimum inhibitory concentration (MIC) testing was performed using VITEK 2 automated system. Each P. aeruginosa isolates showed resistance to Carbapenems (Imipenem and Meropenem) were subjected to Imipenem-EDTA combined disc synergy test (CDST) to investigate the production of MBL (confirmative test). The presence of bla-genes encoded IMP, VIM, and SPM-1 was detected by conventional PCR technique. A total of 75 P. aeruginosa isolates were isolated, 16 (21.3%) were able to grow on MacConkey agar supplemented with Meropenem 4mg/L (MMAC). The MIC of different antibiotics showed that 6 (37.5 %) isolates were Carbapenem resistant, MIC >=16 ug/ml while 4 (25%) isolates appear to be MBL producer using CDST test. PCR assay revealed that 3 (50%), 1 (16.6%) of the carbapenem resistant isolates harbored blaIMP, blaSPM-1 genes, respectively. blaVIM gene was not detected in this study. The prevalence of multi-drug resistant P. aeruginosa isolates especially Carbapenem resistant bacteria was increased in Baghdad province. The blaIMP was the predominant among the MBLs genes in P. aeruginosa in this study. PMID- 26997598 TI - Estimating postoperative survival of gastric cancer patients and factors affecting it in Iran: Based on a TNM-7 Staging System. AB - Recently, reports have shown that gastric cancer has high abundance in Iran and is at the second level in men, and fourth in total. This study aimed to determine the 5-year survival of gastric cancer patients and to investigate factors affecting the performance, based on TNM-7 staging system. In this study, we investigated 760 patients with gastric cancer since the beginning of 1993 to the end of 2006 in the Iran Cancer Institute who underwent surgery. Survival of these patients was determined after surgery, and the effects of demographic characteristics such as age (during operation), sex, and information on diseases such as cancer site, pathologic type, stage of disease progress (Stage), metastasis and sites of metastases were evaluated. The 5 -year survival probability of patients was 28 %, and median survival time was 25.69 months. Univariate tests showed that sex, cancer site, and pathologic type have no significant effects on patient's survival. But the probability of 5-year survival significantly decreases with increasing age, and as it is expected, those with metastases were significantly less likely to have 5-year survival, and disease stage was significantly effective on patients' life (P<0.001). Simultaneous evaluation of different variables' effects on the probability of survival using the multiple Cox proportional hazards models showed that age and stage disease variables were effective on the survival of patients. The 5-year survival of patients with gastric cancer is low in Iran, although it is improved compared to the past. It seems that one of the main reasons for low survival rate of these patients is a late referral of patients for diagnosis and treatment. Most patients refer in the final stages of the disease, at this stage most patients are affected by lymph nodes metastases, liver and as the result, their treatment will be more difficult. PMID- 26997599 TI - Dermatoglyphic's in Congenital Cardiac Disease. AB - Various dermatoglyphic parameters like finger print pattern, atd angle, absolute ridge count & ab, bc ,cd, and ad ridge counts were observed in 150 cases of congenital cardiac disease, comprising of 72 cases of Ventricular Septal Defects (VSD), 60 cases of Atrial Septal Defects (ASD), 9 cases of Coarctation of Aorta (COA) & 9 cases of Tetralogy of Fallot's (TOF). Same dermatoglyphic parameters were also studied in 300 controls and statistical comparison of cases and controls was done. In our study it was observed that the congenital cardiac disease cases exhibited preponderance of whorls (55.8%) with decrease in loop pattern (36.2%) as compared to those of controls and the difference was highly significant (P<0.001). The difference in the mean total finger ridge count (TFRC) of the controls and of the cases of Congenital Cardiac Diseases (CCD) was found to be highly significant (P<0.001), while the mean atd angle in the cases of Congenital Cardiac Disease (CCD) was widen up and was statistically significant too. The mean ab, the mean bc ridge, the mean cd ridge and the mean ad ridge counts were also higher in the various type of CCD as compared to that controls and on statistical comparison, the difference was found to be highly significant. PMID- 26997600 TI - Multivariate Analysis of Factors Influencing Length of Hospital Stay after Coronary Artery Bypass Surgery in Tehran, Iran. AB - Length of hospital stay (LOS) is a key indicator for hospital management. Reducing hospital stay is a priority for all health systems. We aimed to determine the length of hospital stay following Coronary Artery Bypass Surgery (CABG) based on its clinical and non-clinical factors. A cross-sectional study of 649 consecutive patients who underwent coronary artery bypass graft surgery was conducted in Imam Khomeini and Shariati university hospitals, Tehran, Iran. Data was analyzed by using non-parametric univariate tests and multiple linier regression models. Thirty seven independent variables including pre-operative, intra-operative and post-operative variables were analyzed. Finally, an appropriate model was constructed based on the associated factors. The results showed that 70.3% of the patients were male, and the mean age of the patients was 59.3 +/- 10.4 years. The Mean (+/-SD) and median of the LOS were 11.7 +/- 7.1 and 9 days, respectively. Of 37 investigated variables, 24 qualitative and quantitative variables were significantly associated with length of stay (p<0.05). Multiple linear regression analysis showed that independent variables including age, medical insurance type, body mass index, and prior myocardial infarction; admission day, admission season, Cross-clamp time, pump usage, admission type, the number of laboratory tests and the number of specialty consultation had more effect on the hospital stay. We concluded that some significant factors influencing hospital stay after CABG were predictable and modifiable by hospital managers and decision makers to manage hospital beds. PMID- 26997601 TI - The Relation between Diverse Phenotypes of PCOS with Clinical Manifestations, Anthropometric Indices and Metabolic Characteristics. AB - Critical issue regarding to variation of findings based on different phenotypes led investigators to define whether they are distinct features or overlapping ones. Therefore, we aimed to investigate the association between diverse phenotypes of PCOS (Poly Cystic Ovary Syndrome) with clinical manifestations, anthropometric indices, and metabolic characteristics. This was a descriptive cross-sectional study conducted in 15-39 years old women with PCOS referred to infertility clinics in the north part of Iran, Rasht during 2010-2011. Data were gathered through an interview by a form consisted of demographic characteristics, laboratory findings, ovarian volume and anthropometric indices. A total of 214 patients consisted of 161 PCOS (cases) and 53 normal women (controls) participated in this study. The most prevalent phenotype in PCOS population was IM/PCO/HA (54%), followed by IM/HA (28%) and IM/PCO (13%). PCO/HA was present only in 6 PCOS patients (5%). PCOS patients were significantly younger than controls (P=0.07). Results showed that increased ovarian volume were higher in PCOS group in comparison with controls and IM/PCO/HA, and IM/PCO had respectively the largest ovarian volumes. Also, a significant relation was observed based on Cholesterol, 17OHP, LH, TG, 2hpp, and LH/FSH between patients with PCOS and control groups. There were significant differences in demographic, anthropometric, hormonal and ultrasound findings between PCOS and controls. Therefore, it seems that classification of the characteristics of each phenotype could offer an appropriate guide for screening risks of PCOS and may facilitate performing most favorable treatment for these complications. PMID- 26997602 TI - Benefits of Pharmacist's Participation on Hospitalist Team. AB - This study was performed to assess the incidence of medication errors and irrational use of human albumin in two wards of our hospital and also aimed to evaluate the ability of pharmaceutical care center and pharmacists in improving patient care. Albumin administration was evaluated for patients who received albumin during the study period, in gastroenterology and general surgery wards. The indications for Albumin administration were evaluated on the basis of reliable guidelines. The prescribing errors were simultaneously evaluated by reviewing patients' medical records. Prescribing errors were defined as selecting improper drug (based on indications, contraindications, known allergies, drug class duplications and drug-drug interactions), dose, dosage form, and route of administration. It was found that 465 containers of human albumin solution 20 % were used for 54 patients treated in gastroenterology and general surgery wards of our hospital. A total of 306 (65.81%) vials of the albumin administrations were in concordance with the reliable protocol. The cost of irrational use of this drug (159 vials) for patients is equivalent to $ 8215. From 609 reviewed cases, 81 prescribing errors were detected in 64 patients. This study showed that the pharmacists were effective in identifying irrational drug use and medication errors. PMID- 26997603 TI - Vitamin D Deficiency among Female Nurses of Children's Medical Center Hospital and Its Related Factors. AB - Vitamin D deficiency is one of the most preventable challenges worldwide. The aim of this study was to determine the prevalence of vitamin D deficiency among female nurses working at Children's Medical Center Hospital in Tehran, Iran, due to the risk factor of being a notably long period indoors and the fact that their health status may have consequences on the process of patients' treatment. A total of 114 female nurses who were at least 20 years old entered the study voluntarily, and a questionnaire was applied to collect information on lifestyle and other factors associated with vitamin D deficiency. A sample of blood was taken to measure 25-hydroxyvitamin D (25-OHD) and cut off value to indicate deficiency was considered below 10 ng/ml, and the amounts of 10-29 ng/ml were declared insufficient. The mean of 25-OHD was 11.7+/-9.3 ng/ml. A total of 79 subjects (69.3%) had a deficient level of vitamin D, 28 subjects (24.6%) had an insufficient level and only 7 subjects (6.1%) had sufficient level of vitamin D. The deficiency was more noticeable in the age group of 26-35 years old. Prevalence of vitamin D deficiency had a significant correlation with younger subjects (P<0.001). There was no significant association among other factors such as body mass index (BMI), health status complications, regular exercise, and duration of sun exposure. High prevalence of vitamin D deficiency in the study population leads to emphasise the need to screen health care workers for vitamin D levels. PMID- 26997604 TI - Simultaneous External Iliac Artery and Vein Rupture Following Percutaneous Balloon Angioplasty. AB - A 73-year-old woman who had undergone coronary artery bypass grafting for coronary artery stenosis six years ago, presented with right lower extremity claudication. Angiography revealed right external artery stenosis. Elective external iliac PTCA was performed complicated with simultaneous external iliac artery and vein rupture that was an exceedingly rare event. Retroperitoneal laparotomy with repair of ruptures took done, but the patient died with post operative multi-organ failure. PMID- 26997605 TI - A Woman with Normotensive Primary Hyperaldosteronism. AB - Normotensive hyperaldosteronism is a rare disorder. It is usually diagnosed with hypokalemia or an adrenal mass. Our patient was a 27-year-old female presented with weakness. She had normal blood pressure, hypokalemia, high plasma aldosterone level and suppressed plasma renin activity. After the saline load, test aldosterone didn't show suppression. Adrenal computed tomography revealed a left adrenal mass. The patient was treated with spironolactone and potassium supplement. Surgical adrenalectomy was done. Final pathologic diagnosis was benign adrenocortical adenoma without capsular invasion. In postoperative course serum, potassium was normal. PMID- 26997607 TI - [Topical cyclosporine in ophthalmology: Pharmacology and clinical indications]. AB - Cyclosporine A (CsA) is a cyclic undecapeptide, which is an immunosuppressive drug in the calcineurin inhibitor class. CsA was initially used as a systemic immunosuppressant to minimize rejection of solid organ transplants. In ophthalmology, topically applied CsA was first used to inhibit corneal allograft rejection in the 1980s and later in various inflammatory ocular surface disorders (OSD). Currently, topical ophthalmic CsA is available as a licensed commercial emulsion or is prepared by hospital pharmacies with concentration ranging from 0.05 to 2%. Many of its pharmacological effects on the ocular surface are direct consequences of its ability to inhibit T ciclosporine activation and apoptosis. Topical CsA differs from topical steroids in its favourable local and systemic tolerability at the concentrations used. Most clinical studies have evaluated topical CsA in moderate to severe dry eye disease (DED) and demonstrated its efficacy for improvement of signs and symptoms, thus providing the sole indication for market approval and treatment protocols. For the other indications - corneal graft rejection, blepharitis, allergic or viral keratitis, and ocular surface disease due to graft versus host disease or post-operative DED - evidence based medicine remains unclear due to the lack of major randomized controlled trials. Despite the lack of standardized protocols or market approval for these conditions, numerous studies suggest clinical efficacy. PMID- 26997606 TI - Functional annotation of the T-cell immunoglobulin mucin family in birds. AB - T-cell immunoglobulin and mucin (TIM) family molecules are cell membrane proteins, preferentially expressed on various immune cells and implicated in recognition and clearance of apoptotic cells. Little is known of their function outside human and mouse, and nothing outside mammals. We identified only two TIM genes (chTIM) in the chicken genome, putative orthologues of mammalian TIM1 and TIM4, and cloned the respective cDNAs. Like mammalian TIM1, chTIM1 expression was restricted to lymphoid tissues and immune cells. The gene chTIM4 encodes at least five splice variants with distinct expression profiles that also varied between strains of chicken. Expression of chTIM4 was detected in myeloid antigen presenting cells, and in gammadelta T cells, whereas mammalian TIM4 is not expressed in T cells. Like the mammalian proteins, chTIM1 and chTIM4 fusion proteins bind to phosphatidylserine, and are thereby implicated in recognition of apoptotic cells. The chTIM4-immunoglobulin fusion protein also had co-stimulatory activity on chicken T cells, suggesting a function in antigen presentation. PMID- 26997608 TI - The postnatal ontogeny of the sexually dimorphic vocal apparatus in goitred gazelles (Gazella subgutturosa). AB - This study quantitatively documents the progressive development of sexual dimorphism of the vocal organs along the ontogeny of the goitred gazelle (Gazella subgutturosa). The major, male-specific secondary sexual features, of vocal anatomy in goitred gazelle are an enlarged larynx and a marked laryngeal descent. These features appear to have evolved by sexual selection and may serve as a model for similar events in male humans. Sexual dimorphism of larynx size and larynx position in adult goitred gazelles is more pronounced than in humans, whereas the vocal anatomy of neonate goitred gazelles does not differ between sexes. This study examines the vocal anatomy of 19 (11 male, 8 female) goitred gazelle specimens across three age-classes, that is, neonates, subadults and mature adults. The postnatal ontogenetic development of the vocal organs up to their respective end states takes considerably longer in males than in females. Both sexes share the same features of vocal morphology but differences emerge in the course of ontogeny, ultimately resulting in the pronounced sexual dimorphism of the vocal apparatus in adults. The main differences comprise larynx size, vocal fold length, vocal tract length, and mobility of the larynx. The resilience of the thyrohyoid ligament and the pharynx, including the soft palate, and the length changes during contraction and relaxation of the extrinsic laryngeal muscles play a decisive role in the mobility of the larynx in both sexes but to substantially different degrees in adult females and males. Goitred gazelles are born with an undescended larynx and, therefore, larynx descent has to develop in the course of ontogeny. This might result from a trade-off between natural selection and sexual selection requiring a temporal separation of different laryngeal functions at birth and shortly after from those later in life. J. Morphol. 277:826-844, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26997609 TI - The management of pregnancy and delivery in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. AB - 3-hydroxy-3-methylglutaric (HMG)-CoA lyase is required for ketogenesis and leucine degradation. Patients with HMG-CoA lyase deficiency typically present with hypoketotic hypoglycemia and metabolic acidosis, which can be fatal if untreated. The patient is a 28-year-old female with HMG-CoA lyase deficiency who presented at 4 weeks gestation for prenatal care. Protein intake as well as carnitine supplementation were gradually increased to support maternal and fetal demands up to 65 g per day for protein and 80 mg/kg/day for carnitine. Fetal growth was appropriate. At 36 5/7 weeks, she presented with spontaneous rupture of membranes. Twice maintenance 10% glucose-containing intravenous fluids were initiated. During labor, vomiting and metabolic acidosis developed. Delivery was by cesarean. Preeclampsia developed postpartum. The patient recovered well and was discharged home on postpartum day 5. Stress of pregnancy and labor and delivery can lead to metabolic decompensation in HMG-CoA lyase deficiency. Patients should be monitored closely by a biochemical geneticist, dietitian, and high-risk obstetrician at a tertiary care center during their pregnancy. Fasting should be avoided. Intravenous 10% glucose-containing fluids should be provided to prevent catabolism and metabolic decompensation during labor and delivery. (c) 2016 Wiley Periodicals, Inc. PMID- 26997610 TI - Development of a direct blood-based PCR system to detect BLV provirus using CoCoMo primers. AB - Bovine leukemia virus (BLV), the etiologic agent of enzootic bovine leucosis, has caused pandemic outbreaks worldwide. Because transcription of the BLV is quickly blocked after infection, detecting integrated provirus at host genome is an important method of identifying whether an animal is infected. The aim of the present study was to develop a novel direct blood-based PCR system to detect the BLV provirus with high specificity and at low cost. The assay was based on the BLV-CoCoMo degenerate primers, which amplify all known BLV strains. Cattle blood samples (n = 182) were collected from the same BLV-positive farm and subjected to BLV-CoCoMo-direct-PCR to detect the BLV provirus. The proviral load was then estimated. This novel PCR method showed 100 % specificity. The BLV-CoCoMo-direct PCR can be used in a variety of laboratory situations because it does not require expensive equipment/reagents, DNA purification, or a second round of PCR. Therefore, the method is extremely cost-effective and the risk of a false positive result due to DNA contamination is very low. PMID- 26997611 TI - Functional characteristics of the natural polymorphisms of HIV-1 gp41 in HIV-1 isolates from enfuvirtide-naive Korean patients. AB - HIV-1 gp41 plays a key role in viral entry. The insertion of Thr at position 4 and Met/Val/Phe substitutions at position 7 are frequently observed in the fusion peptide (FP) motif of gp41 without major enfuvirtide resistance associated with mutation in heptad repeats 1/2 (HR1/2) of HIV-1 isolates from Korean patients. Here, the influence of these mutations on their biological function was evaluated by employing HIV-1 variants with mutant FPs as shown previously and with recombinant HIV-1 using the env genes of 20 HIV-1 isolates from Korean patients. In an infectivity assay, all FP mutants showed lower infectivity than the wild type NL4-3. In particular, the substitutions at position 7 led to much greater reductions in infectivity than the insertions at position 4. Nevertheless, the replication kinetics of most mutants were similar to those of the wild type, except that the FP mutants with an Ile insertion at position 4 and a Phe substitution at position 7 showed reduced replication. Moreover, most point mutants showed lower IC50 values for enfuvirtide than the wild type, whereas the L7M substitution resulted in a slightly increased IC50 value. The infectivity using the HIV-1 env recombinant viruses decreased in 14 cases but increased slightly in six cases compared with the wild type. Most recombinants were more susceptible to enfuvirtide than the wild type, except for three recombinants that showed slight resistance. Our findings may help to explain the potential mechanisms corresponding to the natural polymorphism of gp41 and to predict the efficiency of enfuvirtide in treatment of HIV-1-infected patients in Korea. PMID- 26997612 TI - Amino acid substitutions occurring during adaptation of an emergent H5N6 avian influenza virus to mammals. AB - Avian influenza viruses (AIVs) are known to cross species barriers, and emergent highly pathogenic H5N6 AIVs pose a serious threat to human health and the poultry industry. Here, we serially passaged an H5N6 virus 10 times in BALB/c mice. The pathogenicity of the wild-type 6D2 (WT-6D2) and mammal-adapted 6D2 strain (MA 6D2) were compared. The viral titer in multiple organs and the death rate for MA 6D2 were significantly higher than for WT-6D2. We provide evidence that the mutations HA A150V, NA R143K and G147E, PB2 E627K, and PA A343T may be important for adaptation of H5N6 AIVs to mammals. PMID- 26997613 TI - In vitro antiviral effect of germacrone on feline calicivirus. AB - Feline calicivirus (FCV) often causes respiratory tract and oral disease in cats and is a highly contagious virus. Widespread vaccination does not prevent the spread of FCV. Furthermore, the low fidelity of the RNA-dependent RNA polymerase of FCV leads to the emergence of new variants, some of which show increased virulence. Currently, few effective anti-FCV drugs are available. Here, we found that germacrone, one of the main constituents of volatile oil from rhizoma curcuma, was able to effectively reduce the growth of FCV strain F9 in vitro. This compound exhibited a strong anti-FCV effect mainly in the early phase of the viral life cycle. The antiviral effect depended on the concentration of the drug. In addition, germacrone treatment had a significant inhibitory effect against two other reference strains, 2280 and Bolin, and resulted in a significant reduction in the replication of strains WZ-1 and HRB-SS, which were recently isolated in China. This is the first report of antiviral effects of germacrone against a calicivirus, and extensive in vivo research is needed to evaluate this drug as an antiviral therapeutic agent for FCV. PMID- 26997614 TI - Genetic diversity of bovine papillomavirus types, including two putative new types, in teat warts from dairy cattle herds. AB - Teat papillomatosis affects dairy cows worldwide. Milking can become difficult due to teat warts, and maintaining affected cows in the herds may diminish economic profit in the dairy industry. Currently, 13 bovine papillomavirus (BPV) types have been fully characterized, and numerous putative BPV types have been identified through partial L1 gene PCR. In order to identify the viral types present in warts on the udders of dairy cows, 40 teat lesions from 24 cows from 13 cattle farms in three States of Brazil were evaluated by PV L1 gene PCR. The warts that were evaluated contained sequences from BPVs 6-10, the putative BPV types BAPV9 and BAPV4, and two unreported putative papillomavirus (PV) types, named BPV/BR-UEL6 and BPV/BR-UEL7. In addition, mixed infections and coinfections were identified, since more than one lesion was observed on the udders of 13 cows. Phylogenetic analysis showed that BPV/BR-UEL6 is closely related to BPVs belonging to the genus Xipapillomavirus, while BPV/BR-UEL7 clustered with the previously reported strains Cervus timorensis and Pudu puda PVs, which represent a putative new PV type, and it was only distantly related to xi-, epsilon-, delta and dyoxi-PVs. These results provide information that will assist in the understanding of the association of BPVs 6, 7, 8, 9, and 10, as well as putative BPV types BAPV4 and BAPV9, with mammary papillomatosis. This is the first characterization of putative novel PV types BPV/BR-UEL6 and BPV/BR-UEL7 in teat warts of dairy cows, highlighting the high genetic diversity of BPVs associated with teat papillomatosis. PMID- 26997615 TI - Numerical analysis of corneal curvature dynamics based on Corvis tonometer images. AB - The paper presents numerical analysis of corneal curvature distribution, based on Corvis ST images. It was shown that a new approach to analysis of corneal curvature from tonometer images enables a better description and understanding of processes during fast corneal deformation. Ten healthy volunteers participated in nine repeated measurements on one eye. 90 sequences of images were processed with software written in Matlab, with the use of the Image Processing Toolbox. Time spatial distribution of the local curvature distribution of the corneal profile was obtained for each and every measurement. Some new curvature parameters were proposed and analyzed. A high repeatability for individual subjects was obtained for the proposed parameters. For four of these new parameters, the ICC coefficients were higher than 0.85. The ICC value for the calculated curvature of the cornea before deformation reaches 0.989. Such high repeatability of the proposed new parameters can be useful in examination and differentiation of corneas due to their geometrical and biomechanical properties. PMID- 26997617 TI - HIV and renal cell carcinoma: Experience in an Australian statewide HIV center. AB - AIM: To report on the presentation, management and outcomes of renal cell carcinoma (RCC) among people with human immunodeficiency virus (HIV). METHODS: We retrospectively reviewed patients with HIV and RCC in a statewide HIV referral center in Australia. Patients' medical records were reviewed to collect data on the HIV parameters at the time of RCC diagnosis, as well as presentation, management and outcomes of RCC. RESULTS: Seven patients with HIV and RCC were included in the current study. The median age at RCC diagnosis was 56 years (range: 44-62 years). At RCC diagnosis, six patients were on combination antiretroviral therapy (ART), and five had virological suppression. Three patients were symptomatic at presentation, while the rest were diagnosed incidentally. Two patients had metastatic RCC at diagnosis. All five patients with clinically localized RCC had radical/partial nephrectomies, of which two patients with pT3a disease developed recurrence (pulmonary and bone) at 5 and 30 months postnephrectomies. One patient with metastatic RCC was treated with vascular endothelial growth factor (VEGF) inhibitors while continuing on ART. Four patients died of RCC at a median of 9 months (range: 4-16 months) following diagnosis of metastatic disease. Three patients were alive at a median follow-up of 16 months (range: 10-80 months). CONCLUSION: Our experience suggests that patients with HIV should be offered all treatment options in the same manner as the general population, taking into account their prognosis from HIV. Curative surgery should be considered for localized RCC. Potential drug interactions between ART drugs and targeted therapies for metastatic RCC need to be considered. PMID- 26997616 TI - Comparison of caries diagnostic modalities: A clinical study in 40 subjects. AB - BACKGROUND AND OBJECTIVES: Few studies have been published that evaluate the usefulness of different caries- diagnostic modalities in general dental practice. The goal of this study was to compare the results of screening for coronal dental caries in a general dental practice using clinical observations, radiographs, laser fluorescence (DIAGNOdentTM) (LF), and optical coherence tomography (OCT). Diagnostic agreement between OCT and LF versus standard clinical techniques for detecting caries was determined in 40 subjects. STUDY DESIGNS/MATERIALS AND METHODS: Forty patients with >1 coronal carious lesion as determined by prescreening using clinical examination and radiographs were enrolled in this study. Subjects with gross caries were excluded. Subsequently each patient underwent a full detailed dental examination by an experienced clinician, using visual examination and radiographs according to standard clinical practice. The coronal surfaces of a total of 932 teeth were examined and charted. Teeth were then photographed, rediagnosed using the LF system, and imaged using OCT. Two blinded pre-standardized examiners reviewed radiographic and OCT images and assigned caries status. RESULTS: Based on manufacturer's cutoff values, sensitivity and specificity for coronal caries using LF technique (i) on unaltered tooth surfaces were 73.7% and 94.1%, respectively and (ii) in previously restored or sealed teeth, they were 19.2% and 95.8%, respectively. LF technique was unable to assess tissue health underneath sealants and restorations. Clinician agreement (kappa [k]) regarding caries diagnosis using OCT imaging was overall 0.834 (SE = 0.034). Sensitivity and specificity for caries using OCT technique (i) on unaltered tooth surfaces approximated 74.1% and 95.7%, respectively and, (ii) in previously restored or sealed teeth, they approximated 76.0% and 95.6%, respectively. Although OCT was able to detect lesions beneath many resin restorations and sealants, results varied considerably between materials. OCT imaging was unable to detect caries when caries was >2 mm below the tooth surface. CONCLUSION: These findings support the usefulness of LF for primary caries detection, and the clinical utility of OCT for early caries detection and monitoring under dental resin restorations and sealants. Lasers Surg. Med. 48:924-928, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26997618 TI - High-Performance Water Electrolysis System with Double Nanostructured Superaerophobic Electrodes. AB - Catalysts screening and structural optimization are both essential for pursuing a high-efficient water electrolysis system (WES) with reduced energy supply. This study demonstrates an advanced WES with double superaerophobic electrodes, which are achieved by constructing a nanostructured NiMo alloy and NiFe layered double hydroxide (NiFe-LDH) films for hydrogen evolution and oxygen evolution reactions, respectively. The superaerophobic property gives rise to significantly reduced adhesion forces to gas bubbles and thereby accelerates the hydrogen and oxygen bubble releasing behaviors. Benefited from these metrics and the high intrinsic activities of catalysts, this WES affords an early onset potential (~1.5 V) for water splitting and ultrafast catalytic current density increase (~0.83 mA mV(-1) ), resulting in ~2.69 times higher performance compared to the commercial Pt/C and IrO2 /C catalysts based counterpart under 1.9 V. Moreover, enhanced performance at high temperature as well as prominent stability further demonstrate the practical application of this WES. PMID- 26997619 TI - Reply. PMID- 26997621 TI - Ion specific effects on the stability of layered double hydroxide colloids. AB - Positively charged layered double hydroxide particles composed of Mg(2+) and Al(3+) layer-forming cations and NO3(-) charge compensating anions (MgAl-NO3-LDH) were synthesized and the colloidal stability of their aqueous suspensions was investigated in the presence of inorganic anions of different charges. The formation of the layered structure was confirmed by X-ray diffraction, while the charging and aggregation properties were explored by electrophoresis and light scattering. The monovalent anions adsorb on the oppositely charged surface to a different extent according to their hydration state leading to the Cl(-) > NO3(-) > SCN(-) > HCO3(-) order in surface charge densities. The ions on the right side of the series induce the aggregation of MgAl-NO3-LDH particles at lower concentrations, whereas in the presence of the left ones, the suspensions are stable even at higher salt levels. The adsorption of multivalent anions gave rise to charge neutralization and charge reversal at appropriate concentrations. For some di, tri and tetravalent ions, charge reversal resulted in restabilization of the suspensions in the intermediate salt concentration regime. Stable samples were also observed at low salt levels. Particle aggregation was fast near the charge neutralization point and at high concentrations. These results, which evidence the colloidal stability of MgAl-NO3-LDH in the presence of various anions, are of prime fundamental interest. These are also critical for applications to develop stable suspensions of primary particles for water purification processes, with the aim of the removal of similar anions by ion exchange. PMID- 26997620 TI - Autoantibodies Specifically Against beta1 Adrenergic Receptors and Adverse Clinical Outcome in Patients With Chronic Systolic Heart Failure in the beta Blocker Era: The Importance of Immunoglobulin G3 Subclass. AB - OBJECTIVE: To elucidate the prevalence and role of beta1 adrenergic receptor autoantibodies (beta1AR-AAb) belonging to the immunoglobulin (Ig)G3 subclass in patients with heart failure (HF) treated with beta-adrenergic blockers. BACKGROUND: Several cardiac AAbs have been reported to be present in sera from patients with dilated cardiomyopathy and other etiologies. Among AAbs, those recognizing beta1AR-AAbs show agonist-like effects, have detrimental effects on cardiomyocytes, and may induce persistent myocardial damage. METHODS: We quantify total IgG and IgG3 subclass beta1AR-AAb in subjects with chronic stable HF with long-term follow-up. RESULTS: In our study cohort of 121 subjects, non-IgG3 beta1AR-AAb and IgG3-beta1AR-AAb were found to be positive in 20 (17%) and 26 patients (21%), respectively. The positive rate of IgG3-beta1AR-AAb was significantly higher for those with nonischemic compared with ischemic HF etiology (27% vs 8%, P = .01), but the positive rate for non-IgG3-beta1AR-AAb was similar between the 2 groups (18% vs 16%, respectively, P = NS). There were no significant differences in clinical and echocardiographic measures among total beta1AR-AAb negative, non-IgG3-beta1AR-AAb positive, and IgG3-beta1AR-AAb positive groups at baseline. During 2.2 +/- 1.2 years of follow-up, we observed similar rates of the composite endpoint of all-cause mortality, cardiac transplantation, or hospitalization resulting from HF between total IgG-beta1AR AAb negative and positive patients. However, the composite endpoint events were significantly more common in the patients without than in those with IgG3-beta1AR AAb (P = .048, log-rank test). CONCLUSIONS: Presence of IgG3-beta1AR-AAb, not total IgG, was associated with paradoxically more favorable outcomes in our cohort of patients with chronic systolic HF largely treated by beta-blockers. PMID- 26997622 TI - Combined pharmacological activation of AMPK and PPARdelta potentiates the effects of exercise in trained mice. AB - The combined activation of the cellular energy sensor AMP-activated protein kinase (AMPK) and the nuclear transcription factor peroxisome proliferator activated receptor delta (PPARdelta) has been demonstrated to improve endurance and muscle function by mimicking the effects of exercise training. However, their combined pharmacological activation with exercise training has not been explored. Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARdelta agonist GW0742 for 4 weeks. AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138-179% and 355% increase in running time, respectively). Despite the lack of change in basal whole-body metabolism, a significant shift to fat as the main energy source with a decline in carbohydrate utilization was observed upon indirect calorimetry analysis at the period near exhaustion. Increased energy substrates before exercise, and elevated muscle nonesterified fatty acids (NEFA) and elevated muscle glycogen at exhaustion were observed together with increased PDK4 mRNA expression. Citrate synthase activity was elevated in AICAR-treated groups, while PGC-1alpha protein level tended to be increased in GW0742-treated groups. At exhaustion, Pgc1a was robustly upregulated together with Pdk4, Cd36, and Lpl in the muscle. A robust upregulation of Pgc1a and a downregulation in Chrebp were observed in the liver. Our data show that combined pharmacological activation of AMPK and PPARdelta potentiates endurance in trained mice by transcriptional changes in muscle and liver, increased available energy substrates, delayed hypoglycemia through glycogen sparing accompanied by increased NEFA availability, and improved substrate shift from carbohydrate to fat. PMID- 26997623 TI - Effect of increased protein intake on renal acid load and renal hemodynamic responses. AB - Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P <= 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P <= 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function. PMID- 26997624 TI - Growth hormone (GH)-transgenic insulin-like growth factor 1 (IGF1)-deficient mice allow dissociation of excess GH and IGF1 effects on glomerular and tubular growth. AB - Growth hormone (GH)-transgenic mice with permanently elevated systemic levels of GH and insulin-like growth factor 1 (IGF1) reproducibly develop renal and glomerular hypertrophy and subsequent progressive glomerulosclerosis, finally leading to terminal renal failure. To dissociate IGF1-dependent and -independent effects of GH excess on renal growth and lesion development in vivo, the kidneys of 75 days old IGF1-deficient (I(-/-)) and of IGF1-deficient GH-transgenic mice (I(-/-)/G), as well as of GH-transgenic (G) and nontransgenic wild-type control mice (I(+/+)) were examined by quantitative stereological and functional analyses. Both G and I(-/-)/G mice developed glomerular hypertrophy, hyperplasia of glomerular mesangial and endothelial cells, podocyte hypertrophy and foot process effacement, albuminuria, and glomerulosclerosis. However, I(-/-)/G mice exhibited less severe glomerular alterations, as compared to G mice. Compared to I(+/+) mice, G mice exhibited renal hypertrophy with a significant increase in the number without a change in the size of proximal tubular epithelial (PTE) cells. In contrast, I(-/-)/G mice did not display significant PTE cell hyperplasia, as compared to I(-/-) mice. These findings indicate that GH excess stimulates glomerular growth and induces lesions progressing to glomerulosclerosis in the absence of IGF1. In contrast, IGF1 represents an important mediator of GH-dependent proximal tubular growth in GH-transgenic mice. PMID- 26997625 TI - Early diabetic kidney maintains the corticomedullary urea and sodium gradient. AB - Early diabetic nephropathy is largely undetectable before substantial functional changes have occurred. In the present study, we investigated the distribution of electrolytes and urea in the early diabetic kidney in order to explore whether pathophysiological and metabolic changes appear concomitantly with a decreased sodium and urea gradient. By using hyperpolarized (13)C urea it was possible to measure the essential intrarenal electrolyte gradients and the acute changes following furosemide treatment. No differences in either intrarenal urea or sodium gradients were observed in early diabetes compared to healthy controls. These results indicate that the early metabolic and hypertrophic changes occurring in the diabetic kidney prelude the later functional alterations in diabetic kidney function, thus driving the increased metabolic demand commonly occurring in the diabetic kidney. PMID- 26997626 TI - The cardiovascular response to passive movement is joint dependent. AB - The cardiovascular responses to passive limb movement (PLM) at the knee are well established, however, responses to PLM at other joints involving smaller muscle volume are unknown. To compare the cardiovascular responses to passive movement at other joints, 10 participants underwent a PLM protocol in which the wrist, elbow, ankle, and knee joints were passively extended and flexed at 1 Hz for 1 min. Heart rate (HR), mean arterial blood pressure (MAP), and arterial blood flow to that limb segment (BF) were measured and vascular conductance (VC) was calculated for a 30-sec baseline period and for 3-sec intervals throughout PLM protocols. PLM of the knee and elbow resulted in significant increases in BF and VC from baseline values with peak values 180% (P < 0.001) greater than baseline. PLM of the elbow resulted in significant increases in BF and VC from baseline values with peak values 109% and 115% (P < 0.001) greater than baseline, respectively. No changes in BF and VC were observed in the ankle and wrist. Furthermore, the greater increase in blood flow per limb segment volume in the thigh and upper arm (62.8 +/- 36.5 and 55.5 +/- 30.3 mL min(-1) L(-1), respectively) compared to the forearm and lower leg (23.6 +/- 16.7 and 19.1 +/- 10.3 mL min(-1) L(-1), respectively) indicates the limb volume is not solely responsible for the differences in the hyperemic responses. These data indicate that the use of PLM to assess vascular function or as a rehabilitation modality to maintain vascular health may be most appropriate for the muscles that span the elbow and knee. PMID- 26997627 TI - Role of prolyl hydroxylase domain proteins in the regulation of insulin secretion. AB - Type 2 diabetes is associated with impaired nutrient-regulated anaplerosis and insulin secretion in pancreatic beta-cells. One key anaplerotic substrate that may be involved in regulating insulin release is alpha-ketoglutarate (alphaKG). Since prolyl hydroxylase domain proteins (PHDs) can metabolize cytosolic alphaKG, we sought to explore the role of this enzyme in the regulation of beta-cell function. The oxygen-sensing PHDs regulate the stability of hypoxia-inducible factor 1alpha (HIF1alpha) as well as other proline-containing proteins by catalyzing the hydroxylation of proline residues. This reaction is dependent on sufficient levels of oxygen, iron, and alphaKG. In the present study, we utilized both pharmacological and genetic approaches to assess the impact of inhibiting PHD activity on beta-cell function. We demonstrate that ethyl-3,4 dihydroxybenzoate (EDHB), a PHD inhibitor, significantly blunted glucose stimulated insulin secretion (GSIS) from 832/13 clonal cells, rat, and human islets. EDHB reduced glucose utilization, ATP/ADP ratio, and key TCA cycle intermediates such as pyruvate, citrate, fumarate, and malate. siRNA-mediated knockdown of PHD1 and PHD3 inhibited GSIS, whereas siRNA-mediated knockdown of PHD2 had no effect on GSIS. Taken together, the current results demonstrate an important role for PHDs as mediators of islet insulin secretion. PMID- 26997628 TI - Aberrant nonfibrotic parenchyma in idiopathic pulmonary fibrosis is correlated with decreased beta-catenin inhibition and increased Wnt5a/b interaction. AB - Idiopathic pulmonary fibrosis (IPF), an insidious disease with grave prognosis, is characterized by heterogeneous fibrosis with densely fibrotic areas surrounded by nonfibrotic normal-looking tissue, believed to reflect a temporal development. The etiology is incompletely elucidated, but aberrant wound healing is believed to be involved. Embryonic signaling pathways, including Wnt signaling, are reactivated in wound healing, and we therefore aimed to investigate Wnt signaling, and hypothesized that Wnt signaling would correspond to degree of fibrosis. Material from 10 patients with IPF were included (four diagnostic biopsies and six donated lungs) and compared to healthy controls (n = 7). We investigated markers of Wnt signaling (beta-catenin, Wnt3a, ICAT, Wnt5a/b, DAAM1 and NLK) histologically in lung parenchyma with variable degree of fibrosis. Our results suggest that Wnt signaling is significantly altered (P < 0.05) already in normal-looking parenchyma. The expression of Wnt3a and ICAT decreased (both P < 0.01) in IPF compared to healthy lungs, whereas beta-catenin, Wnt5a/b, DAAM1 and NLK increased (P < 0.05 for all). ICAT is further decreased in dense fibrosis compared to normal-looking parenchyma in IPF (P < 0.001). On the basis of our results, we conclude that from a Wnt perspective, there is no normal parenchyma in IPF, and Wnt signaling corresponds to degree of fibrosis. In addition, beta catenin and Wnt5a appears coupled, and decreased inhibition of beta-catenin may be involved. We suggest that the interaction between beta-catenin, ICAT, and Wnt5a/b may represent an important research area and potential target for therapeutic intervention. PMID- 26997629 TI - An ectopic renin-secreting adrenal corticoadenoma in a child with malignant hypertension. AB - A previously healthy 7-year-old male presented with hypertensive emergency, hypokalemia, and elevated plasma renin activity and aldosterone levels. There was no evidence of virilization or cushingoid features. MRI of the abdomen revealed a large (5 * 5 * 3 cm) peripherally enhancing, heterogeneous mass arising from the left adrenal gland. The patient was treated for a suspected pheochromocytoma. However, his blood pressure was not responsive to alpha-blockade. Blood pressure was controlled with a calcium channel blocker and an angiotensin-converting enzyme (ACE) inhibitor. A complete surgical resection of the mass was performed. Postoperatively, his blood pressure normalized and he did not require antihypertensives. On pathological examination, the tumor tissue stained negative for chromogranin and positive for renin. The final diagnosis was renin-secreting adrenal corticoadenoma, an extremely rare adrenal tumor not previously reported in a pediatric patient. Malignant hypertension due to a renin-secreting tumor may need to be distinguished from a pheochromocytoma if alpha-adrenergic blockade is ineffective. PMID- 26997630 TI - The Na+/H+ exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension. AB - Increased muscularity of small pulmonary vessels, involving enhanced proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a key component of the vascular remodeling underlying the development of pulmonary hypertension (PH). Stimuli such as growth factors and hypoxia induce PASMC alkalinization, proliferation, and migration through upregulation of the Na(+)/H(+) exchanger (NHE), inhibition of which prevents the development of hypoxia-induced vascular remodeling and PH. We wanted to explore whether NHE was also necessary for pathologic PASMC proliferation and migration in a model of pulmonary arterial hypertension (PAH), a severe form of PH not associated with persistent hypoxia. PASMCs were isolated from rats exposed to SU5416-hypoxia (SuHx) followed by return to normoxia and from vehicle controls. We measured resting intracellular pH (pHi) and NHE activity using the pH-sensitive fluorescent dye BCECF-AM. PASMC proliferation and migration were assessed using BrdU incorporation and transwell filters, respectively. NHE activity was increased in SuHx PASMCs, although resting pHi was unchanged. SuHx PASMCs also exhibited increased proliferation and migration relative to controls, which was attenuated in the setting of pharmacologic inhibition of NHE. Our findings suggest that increased NHE activity contributes to pathologic PASMC function in the SuHx model of PAH, although this effect does not appear to be mediated by global changes in pHi homeostasis. PMID- 26997631 TI - Myocardial dysfunction occurs prior to changes in ventricular geometry in mice with chronic kidney disease (CKD). AB - Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD), but the underlying mechanisms contributing to this complex phenotype are incompletely understood. Myocardial deformation analyses (ventricular strain) of patients with mild CKD have recently been reported to predict adverse clinical outcome. We aimed to determine if early myocardial dysfunction in a mouse model of CKD could be detected using ventricular strain analyses. CKD was induced in 5-week-old male 129X1/SvJ mice through partial nephrectomy (5/6Nx) with age-matched mice undergoing bilateral sham surgeries serving as controls. Serial transthoracic echocardiography was performed over 16 weeks following induction of CKD. Invasive hemodynamic measurements were performed at 8 weeks. Gene expression and histology was performed on hearts at 8 and 16 weeks. CKD mice developed decreased longitudinal strain (-25 +/- 4.2% vs. -29 +/- 2.3%; P = 0.01) and diastolic dysfunction (E/A ratio 1.2 +/- 0.15 vs. 1.9 +/- 0.18; P < 0.001) compared to controls as early as 2 weeks following 5/6Nx. In contrast, ventricular hypertrophy was not apparent until 4 weeks. Hearts from CKD mice developed progressive fibrosis at 8 and 16 weeks with gene signatures suggestive of evolving heart failure with elevated expression of natriuretic peptides. Uremic cardiomyopathy in this model is characterized by early myocardial dysfunction which preceded observable changes in ventricular geometry. The model ultimately resulted in myocardial fibrosis and increased expression of natriuretic peptides suggestive of progressive heart failure. PMID- 26997633 TI - Effect of tidal volume and positive end-expiratory pressure on expiratory time constants in experimental lung injury. AB - We utilized a multicompartment model to describe the effects of changes in tidal volume (VT) and positive end-expiratory pressure (PEEP) on lung emptying during passive deflation before and after experimental lung injury. Expiratory time constants (tauE) were determined by partitioning the expiratory flow-volume (VEV) curve into multiple discrete segments and individually calculating tauE for each segment. Under all conditions of PEEP and VT, tauE increased throughout expiration both before and after injury. Segmented tauE values increased throughout expiration with a slope that was different than zero (P < 0. 01). On average, tauE increased by 45.08 msec per segment. When an interaction between injury status and tauE segment was included in the model, it was significant (P < 0.05), indicating that later segments had higher tauE values post injury than early tauE segments. Higher PEEP and VT values were associated with higher tauE values. No evidence was found for an interaction between injury status and VT, or PEEP. The current experiment confirms previous observations that tauE values are smaller in subjects with injured lungs when compared to controls. We are the first to demonstrate changes in the pattern of tauE before and after injury when examined with a multiple compartment model. Finally, increases in PEEP or VT increased tauE throughout expiration, but did not appear to have effects that differed between the uninjured and injured state. PMID- 26997634 TI - Biological effect of LOXL1 coding variants associated with pseudoexfoliation syndrome. AB - Pseudoexfoliation (PEX) syndrome is a systemic disease involving the extracellular matrix. It increases the risk of glaucoma, an irreversible cause of blindness, and susceptibility to heart disease, stroke and hearing loss. Single nucleotide polymorphisms (SNPs) in the LOXL1 (Lysyl oxidase-like 1) gene are the major known genetic risk factor for PEX syndrome. Two coding SNPs, rs1048861 (G > T; Arg141Leu) and rs3825942 (G > A; Gly153Asp), in the LOXL1 gene are strongly associated with the disease risk in multiple populations worldwide. In the present study, we investigated functional effects of these SNPs on the LOXL1 protein. We show through molecular modelling that positions 141 and 153 are likely surface residues and hence possible recognition sites for protein-protein interactions; the Arg141Leu and Gly153Asp substitutions cause charge changes that would lead to local differences in protein electrostatic potential and in turn the potential to modify protein-protein interactions. In RFL-6 rat fetal lung fibroblast cells ectopically expressing the LOXL1 protein variants related to PEX (Arg141_Gly153, Arg141_Asp153 or Leu141_Gly153), immunoprecipitation of the secreted variants showed differences in their processing by endogenous proteins, possibly Bone morphogenetic protein-1 (BMP-1) that cleaves and leads to enzymatic activation of LOXL1. Immunofluorescence labelling of the ectopically expressed protein variants in RFL-6 cells showed no significant difference in their extracellular accumulation tendency. In conclusion, this is the first report of a biological effect of the coding SNPs in the LOXL1 gene associated with PEX syndrome, on the LOXL1 protein. The findings indicate that the disease associated coding variants themselves may be involved in the manifestation of PEX syndrome. PMID- 26997632 TI - Immunomodulatory roles of CTRP3 in endotoxemia and metabolic stress. AB - C1q/TNF-related protein 3 (CTRP3) is a secreted hormone that modulates hepatic glucose and lipid metabolism. Its circulating levels are reduced in human and rodent models of obesity, a metabolic state accompanied by chronic low-grade inflammation. Recent studies have demonstrated an anti-inflammatory role for recombinant CTRP3 in attenuating LPS-induced systemic inflammation, and its deficiency markedly exacerbates inflammation in a mouse model of rheumatoid arthritis. We used genetic mouse models to explore the immunomodulatory function of CTRP3 in response to acute (LPS challenge) and chronic (high-fat diet) inflammatory stimuli. In a sublethal dose of LPS challenge, neither CTRP3 deficiency nor its overexpression in transgenic mice had an impact on IL-1beta, IL-6, TNF-alpha, or MIP-2 induction at the serum protein or mRNA levels, contrary to previous findings based on recombinant CTRP3 administration. In a metabolic context, we measured 71 serum cytokine levels in wild-type and CTRP3 transgenic mice fed a high-fat diet or a matched control low-fat diet. On a low-fat diet, CTRP3 transgenic mice had elevated circulating levels of multiple chemokines (CCL11, CXCL9, CXCL10, CCL17, CX3CL1, CCL22 and sCD30). However, when obesity was induced with a high-fat diet, CTRP3 transgenic mice had lower circulating levels of IL-5, TNF-alpha, sVEGF2, and sVEGFR3, and a higher level of soluble gp130. Contingent upon the metabolic state, CTRP3 overexpression altered chemokine levels in lean mice, and attenuated systemic inflammation in the setting of obesity and insulin resistance. These results highlight a context-dependent immunomodulatory role for CTRP3. PMID- 26997635 TI - Outbreak of Kyasanur Forest disease (monkey fever) in Sindhudurg, Maharashtra State, India, 2016. PMID- 26997636 TI - Epidemiology of nontuberculous mycobacteria isolations among central North Carolina residents, 2006-2010. AB - BACKGROUND: Nontuberculous mycobacteria (NTM) are environmental mycobacteria associated with a range of infections. Reports of NTM epidemiology have primarily focused on pulmonary infections and isolations, however extrapulmonary infections of the skin, soft tissues and sterile sites are less frequently described. METHODS: We comprehensively reviewed laboratory reports of NTM isolation from North Carolina residents of three counties during 2006-2010. We describe age, gender, and race of patients, and anatomic site of isolation for NTM species. RESULTS: Among 1033 patients, overall NTM isolation prevalence was 15.9/100,000 persons (13.7/100,000 excluding Mycobacterium gordonae). Prevalence was similar between genders and increased significantly with age. Extrapulmonary isolations among middle-aged black males and pulmonary isolations among elderly white females were most frequently detected. Most isolations from pulmonary sites and blood cultures were Mycobacterium avium complex; rapidly growing NTM (e.g. Mycobacterium chelonae, Mycobacterium fortuitum) were most often isolated from paranasal sinuses, wounds and skin. CONCLUSIONS: We provide the first characterization of NTM isolation prevalence in the Southeastern United States (U.S.). Variation in isolation prevalence among counties and races likely represent differences in detection, demographics and risk factors. Further characterization of NTM epidemiology is increasingly important as percentages of immunocompromised individuals and the elderly increase in the U.S. PMID- 26997637 TI - TRAIL and IP-10 as biomarkers of viral infections in the emergency department. PMID- 26997638 TI - A comment about "Profession at the crossroads: A dialog concerning the preparation of nursing scholars and leaders". PMID- 26997639 TI - Structuring Au nanoparticles on two-dimensional MoS2 nanosheets for electrochemical glucose biosensors. AB - Two-dimensional (2D) bioelectronics is an emerging field of research which fuses the advantages of 2D nanomaterials with those of nanobiotechnology. Due to the various physical and chemical properties present in layered counterparts of 2D materials, including high charge density, large surface area, remarkable electron mobility, ready electron transport, sizeable band gaps and ease of hybridisation, they are set to become a versatile tool to fabricate sensitive and selective novel biodevices, which might offer an unique advantages to tackle key energy, medical and environmental issues. Current 2D bioelectronics research is focused on the design of simple-to-use and cheaper biodevices, while improving their selectivity, sensitivity and stability. However, current designs generally suffer from a lack of efficiency, relatively low sensitivity, slow electron transfer kinetics, high background charging current and low current density arising from poor mass transport. Here, we report a nanoparticle-structured MoS2 nanosheet as an ideal semiconductor interface, which is able to form a homogenous layer on the electrode surface for the assembly of gold nanoparticles. This not only enhances electrocatalytic reactions, but also provides excellent electrochemical properties such as high faradic-to-capacitive current ratios, high current density and electron mobility, and faster mass transport, due to the dominance of radial diffusion. The MoS2/Au NPs/GOx bioelectrode exhibits a linear response to glucose from 0.25 to 13.2mM, with a detection limit of 0.042uM (S/N=3) and sensitivity of 13.80uA/uM/cm2. PMID- 26997640 TI - Ulcerative colitis endoscopic index of severity is associated with long-term prognosis in ulcerative colitis patients treated with infliximab. AB - BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is characterized by periods of remission and episodes of relapse. Mucosal healing is an emerging therapeutic target in UC and various scoring systems have been used. The UC endoscopic index of severity (UCEIS) is the only validated endoscopic index at present, with minimum interobserver variation. Correlation of UCEIS scores after treatment and clinical outcomes of UC has not been examined. In the present study, we aimed to evaluate the usefulness of UCEIS after treatment with infliximab. METHODS: The medical records of 82 UC patients, treated with infliximab at Keio University Hospital between October 2010 and July 2013, were reviewed retrospectively. Endoscopic findings were evaluated based on the UCEIS. RESULTS: Mean pre-therapeutic UCEIS score was 5.1. Pre-therapeutic UCEIS scores were not associated with short-term outcomes. Forty-five patients underwent colonoscopy at 3-12 months after starting treatment; mean post therapeutic UCEIS score was 2.4, with a score of 0-1 in 16 (35.6%) patients, 2-4 in 19 (42.2%) patients, and 5-8 in 10 (22.2%) patients. Importantly, a post therapeutic UCEIS score of 0 or 1 after treatment was associated with a favorable long-term outcome. CONCLUSION: UCEIS score is a useful instrument for evaluating endoscopic improvement in UC patients treated with infliximab, and mucosal healing may be defined with a UCEIS score of 0 or 1. PMID- 26997641 TI - Anti-peptidyl-arginine deaminase 3 (PAD3) antibodies as a promising marker to measure joint damage in patients with rheumatoid arthritis. AB - BACKGROUND: Recently, antibodies directed against peptidyl arginine deiminase 3 and 4 (anti-PAD3/PAD4 antibodies), calcium-dependent enzymes that catalyze the conversion from arginine to citrulline, have been described. Furthermore, antibodies that cross-react between PAD3 and PAD4 cause increased PAD4 activity and consequently correlate with joint damage. This study analyzes the correlation of anti-PAD3 antibodies with joint damage. METHODS: To validate the novel chemiluminescent immunoassay (CIA) for the detection of anti-PAD3 antibodies, 20 samples were tested by CIA and by immunoprecipitation (IP). Next, 39 RA patients with available joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS) were tested for anti-CCP (using different methods) and anti-PAD3 antibodies by CIA. RESULTS: Excellent correlation was observed between the CIA and IP for the detection of anti-PAD3 antibodies (rho=0.85, p<0.0001). The median JES of our 39 patients was 14.1 with a standard deviation of 11.5. Anti-PAD3 antibody levels (rho=0.39, 95% CI=0.1-0.6; p=0.0149) were correlated with JES. No correlation was found with TSS and JSNS. In this cohort, ACPA measured using different anti-CCP assays did not correlate with the JES. CONCLUSION: In our cohort, anti-PAD3 antibodies correlate with joint erosion score. Therefore, anti-PAD3 antibodies might represent promising markers to predict joint damage in RA patients. PMID- 26997642 TI - Classification of patients with non-alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers. AB - AIM: Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). We investigated the association among serum type IV collagen level, liver histology, and other fibrosis markers in NAFLD progression. METHODS: We evaluated 184 patients diagnosed with NAFLD following biopsy, including 89 males and 95 females with an average age of 52.6 and 62.6 years, respectively. Non-alcoholic fatty liver disease was classified as NAFL or NASH using Matteoni's classification, and the grade and stage of NASH were assessed using Brunt's classification. Serum type IV collagen was measured by a rapid and sensitive latex particle-enhanced turbidimetric immunoassay. RESULTS: Forty-two patients with NAFL and 142 patients with NASH were included in this study. Compared with patients with NAFL, patients with NASH showed more significant liver function disorder and increased expression of fibrosis markers including type IV collagen, collagen 7S, Mac2 binding protein (M2BP), and hyaluronic acid (HA). Expression of type IV collagen and collagen 7S, but not M2BP and HA, was more significantly elevated in patients with stage 1 NASH than in patients with NAFL, indicating that type IV collagen and collagen 7S may be better discriminators of NASH and NAFL than M2BP and HA at an early stage of fibrosis. When patients were stratified by NAFLD activity score, type IV collagen and collagen 7S were significantly elevated as NAFLD activity score progressed, whereas M2BP and HA expression were not significantly elevated. CONCLUSION: Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely. PMID- 26997643 TI - Issues in driving impairment. PMID- 26997644 TI - Estradiol Facilitates Functional Integration of iPSC-Derived Dopaminergic Neurons into Striatal Neuronal Circuits via Activation of Integrin alpha5beta1. AB - For cell transplantation therapy for Parkinson's disease (PD) to be realized, the grafted neurons should be integrated into the host neuronal circuit to restore the lost neuronal function. Here, using wheat-germ agglutinin-based transsynaptic tracing, we show that integrin alpha5 is selectively expressed in striatal neurons that are innervated by midbrain dopaminergic (DA) neurons. In addition, we found that integrin alpha5beta1 was activated by the administration of estradiol-2-benzoate (E2B) in striatal neurons of adult female rats. Importantly, we observed that the systemic administration of E2B into hemi-parkinsonian rat models facilitates the functional integration of grafted DA neurons derived from human induced pluripotent stem cells into the host striatal neuronal circuit via the activation of integrin alpha5beta1. Finally, methamphetamine-induced abnormal rotation was recovered earlier in E2B-administered rats than in rats that received other regimens. Our results suggest that the simultaneous administration of E2B with stem cell-derived DA progenitors can enhance the efficacy of cell transplantation therapy for PD. PMID- 26997646 TI - Zscan4 Is Activated after Telomere Shortening in Mouse Embryonic Stem Cells. AB - ZSCAN4 is a DNA-binding protein that functions for telomere elongation and genomic stability. In vivo, it is specifically expressed at the two-cell stage during mouse development. In vitro, it is transiently expressed in mouse embryonic stem cells (ESCs), only in 5% of the population at one time. Here we attempted to elucidate when, under what circumstances, Zscan4 is activated in ESCs. Using live cell imaging, we monitored the activity of Zscan4 together with the pluripotency marker Rex1. The lengths of the cell cycles in ESCs were diverse. Longer cell cycles were accompanied by shorter telomeres and higher activation of Zscan4. Since activation of Zscan4 is involved in telomere elongation, we speculate that the extended cell cycles accompanied by Zscan4 activation reflect the time for telomere recovery. Rex1 and Zscan4 did not show any correlation. Taken together, we propose that Zscan4 is activated to recover shortened telomeres during extended cell cycles, irrespective of the pluripotent status. PMID- 26997645 TI - An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development. AB - EWS-FLI1, a multi-functional fusion oncogene, is exclusively detected in Ewing sarcomas. However, previous studies reported that rare varieties of osteosarcomas also harbor EWS-ETS family fusion. Here, using the doxycycline-inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also show that sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited an impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrate that EWS-FLI1 contributed to secondary sarcoma development from the sarcoma iPSCs after osteogenic differentiation. These findings demonstrate that modulating cellular differentiation is a fundamental principle of EWS-FLI1-induced osteosarcoma development. This in vitro cancer model using sarcoma iPSCs should provide a unique platform for dissecting relationships between the cancer genome and cellular differentiation. PMID- 26997648 TI - Chemical composition and in vitro evaluation of antioxidant, antimicrobial, cytotoxicity and anti-acetylcholinesterase properties of Tunisian Origanum majorana L. essential oil. AB - This study investigated the chemical composition and evaluated the antioxidant, antimicrobial, cytotoxic and anti-acetylcholinesterase properties of Tunisian Origanum majorana essential oil. The findings showed that the oil exhibited high activity, particularly in terms of reducing power and beta-Carotene bleaching, inducing higher IC50 values than BHT. The oil showed an important antimicrobial activity against 25 bacterial and fungal strains. In fact, the IZ, MIC and MBC values recorded for the bacterial strains were in the range of 8 +/- 0-18.33 +/- 0.57 mm, 0.097-3.125 and 0.39-6.25 mg/mL, respectively. The IZ, MIC and MFC values of the fungal strains varied between 11+/-0-28 +/- 0 mm, 0.058-0.468 mg/mL and 0.234-1.875 mg/mL, respectively. A low cytotoxic effect was observed against cancer (Hep-2 and HT29) and continuous cell lineage (Vero), with CC50 values ranging from 13.73 to 85.63 mg/mL. The oil was also evaluated for anti acetylcholinesterase effects, which showed that it exhibited significant activity with IC50 values reaching 150.33 +/- 2.02 MUg/mL. PMID- 26997649 TI - Persistent Mycobacterium bovis-BCG is resistant to glutathione induced reductive stress killing. AB - This study focuses on the redox stress response in mycobacteria elicited by a host-derived, thiol-based detoxification molecule, glutathione (GSH). Although the growth and viability of Mycobacterium bovis-BCG (BCG) was hampered by exposure to 8 mM GSH, oxygen depleted, persistent BCG (NRP BCG) resisted GSH mediated killing. Fast growing mycobacteria also resisted GSH-mediated killing. To determine the mechanisms behind these observations, we evaluated the levels of intracellular ATP in both BCG and NRP BCG exposed to 8 mM GSH. Intracellular ATP levels increased from 0.13 to 2.3 MUM in BCG upon exposure to GSH. The levels of ATP remained low and unchanged when NRP BCG was exposed to GSH. Using both HPLC and a cell-based thiol detection assay, it was determined that GSH stimulates the production of mycothiol (MSH) by BCG approximately 5.7 fold. The levels of MSH did not change upon exposure of NRP BCG to GSH. MSH is an alternative, thiol based detoxification molecule employed by mycobacteria. Changes in the cytoplasmic concentrations of this molecule are suggestive of redox imbalances. Together, GSH and MSH may introduce excess reducing equivalents into the mycobacterial cytoplasm; leading to reductive stress. The modulation of NAD(+) levels through alterations in ATP metabolism can enhance the cells ability to bind excess reducing equivalents and serve as a mechanism to restore the cellular redox balance when cells experience reductive stress. These data suggest that killing of BCG by GSH may result from reductive stress that cannot be controlled. NRP BCG appears to be resistant to GSH-induced reductive stress. PMID- 26997647 TI - Establishment of In Vitro FUS-Associated Familial Amyotrophic Lateral Sclerosis Model Using Human Induced Pluripotent Stem Cells. AB - Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disorder. Although its neuropathology is well understood, the cellular and molecular mechanisms are yet to be elucidated due to limitations in the currently available human genetic data. In this study, we generated induced pluripotent stem cells (iPSC) from two familial ALS (FALS) patients with a missense mutation in the fused-in sarcoma (FUS) gene carrying the heterozygous FUS H517D mutation, and isogenic iPSCs with the homozygous FUS H517D mutation by genome editing technology. These cell-derived motor neurons mimicked several neurodegenerative phenotypes including mis-localization of FUS into cytosolic and stress granules under stress conditions, and cellular vulnerability. Moreover, exon array analysis using motor neuron precursor cells (MPCs) combined with CLIP-seq datasets revealed aberrant gene expression and/or splicing pattern in FALS MPCs. These results suggest that iPSC-derived motor neurons are a useful tool for analyzing the pathogenesis of human motor neuron disorders. PMID- 26997651 TI - Effects of extracerebral dopamine on salsolinol- or thyrotropin-releasing hormone induced prolactin (PRL) secretion in goats. AB - The aim of the present study was to clarify the effect of extracerebral dopamine (DA) on salsolinol (SAL)-induced prolactin (PRL) secretion in goats. An intravenous injection of SAL or thyrotropin-releasing hormone (TRH) was given to female goats before and after treatment with an extracerebral DA receptor antagonist, domperidone (DOM), and the PRL-releasing response to SAL was compared with that to TRH. DOM alone increased plasma PRL concentrations and the PRL releasing response to DOM alone was greater than that to either SAL alone or TRH alone. The PRL-releasing response to DOM plus SAL was similar to that to DOM alone, and no additive effect of DOM and SAL on the secretion of PRL was observed. In contrast, the PRL-releasing response to DOM plus TRH was greater than that to either TRH alone or DOM alone and DOM synergistically increased TRH induced PRL secretion. The present results demonstrate that the mechanism involved in PRL secretion by SAL differs from that by TRH, and suggest that the extracerebral DA might be associated in part with the modulation of SAL-induced PRL secretion in goats. PMID- 26997650 TI - First report of novel genetic array aacA4-blaIMP-25-oxa30-catB3 and identification of novel metallo-beta-lactamase gene blaIMP25: A Retrospective Study of antibiotic resistance surveillance on Psuedomonas aeruginosa in Guangzhou of South China, 2003-2007. AB - Carbapenem, imipenem and meropenem have been broadly prescribed contributing to the global occurrence and prevalence of carbapenem resistance in Psuedomonas aeruginosa, and the associated resistance genotypes remains clinically significant. A retrospective surveillance had been conducted on 499 P. aeruginosa isolates in South China during 2003-2007, including antimicrobial resistance and characterization of MBLs on carbapenem-resistant strains. One hundred and sixty four out of 499 strains were carbapenem-resistant, with 11, 4 and 5 strains positive for blaIMP-9, blaIMP-25 and blaVIM-2, respectively. Sixteen out of 20 isolates were positive for intI1 and contained identical flanking regions (as indicated in KM384735), and all tested isolates containing the qacE?1-sul1 of the typical 3'-conserved region. A novel blaIMP-25 metallo-beta-lactamase and a genetic array of aacA4-blaIMP-25-oxa30-catB3 have been discovered from this retrospective surveillance on antimicrobial resistance of P. aeruginosa. PMID- 26997652 TI - Changes in the Small Intestine of a Cat Associated with Barium Sulphate Following Contrast Radiography. AB - A 7-year-old neutered male domestic short-haired cat that had undergone contrast radiography of the bowel with barium sulphate after acute episodes of vomiting 2 months previously, was presented with chronic vomiting, anorexia and weight loss. Abdominal radiography and ultrasonography revealed residual contrast enhancement and an obstruction of the small intestine. A contracted and stenosed ileum and distal jejunum were identified by exploratory laparotomy and surgically resected; subsequently, the clinical signs resolved. Histopathological examination of the ileum revealed mucosal ulceration with severe submucosal granulation tissue formation associated with scattered foreign crystalline material. Energy dispersive X-ray spectroscopy revealed that the crystals contained barium sulphate. This is the first report in animals of the rare complication of barium sulphate incorporation into the gastrointestinal mucosa after contrast radiography. PMID- 26997653 TI - P4 functionalization by hydrides: direct synthesis of P-H bonds. AB - A direct method for white phosphorus functionalization by hydride sources is presented. Excess BH4(-) in n-butylamine produces HP4(-) as the major P containing species. Reaction with LiBEt3H forms the borane-stabilized phosphanide Li(PH2)(BEt3)2, which may be used to synthesize various phosphines. Triethylborane may be replaced by BH3, resulting in the formation of LiPH2(BH3)2. PMID- 26997654 TI - Motor dual-tasking deficits predict falls in Parkinson's disease: A prospective study. AB - INTRODUCTION: Falls severely affect lives of Parkinson's disease (PD) patients. Cognitive impairment including dual-tasking deficits contribute to fall risk in PD. However, types of dual-tasking deficits preceding falls in PD are still unclear. METHODS: Walking velocities during box-checking and subtracting serial 7s were assessed twice a year in 40 PD patients over 2.8 +/- 1.0 years. Fourteen patients reported a fall within this period (4 excluded fallers already reported falls at baseline). Their dual-task costs (DTC; mean +/- standard deviation) 4.2 +/- 2.2 months before the first fall were compared with 22 patients never reporting falls. ROC analyses and logistic regressions accounting for DTC, UPDRS III and disease duration were used for faller classification and prediction. RESULTS: Only walking/box-checking predicted fallers. Fallers showed higher DTC for walking while box-checking, p = 0.029, but not for box-checking while walking, p = 0.178 (combined motor DTC, p = 0.022), than non-fallers. Combined motor DTC classified fallers and non-fallers (area under curve: 0.75; 95% confidence interval, CI: 0.60-0.91) with 71.4% sensitivity (95%CI: 41.9%-91.6%) and 77.3% specificity (54.6%-92.2%), and significantly predicted future fallers (p = 0.023). Here, 20.4%-points higher combined motor DTC (i.e. the mean difference between fallers and non-fallers) was associated with a 2.6 (1.1-6.0) times higher odds to be a future faller. CONCLUSION: Motor dual-tasking is a potentially valuable predictor of falls in PD, suggesting that avoiding dual task situations as well as specific motor dual-task training might help to prevent falls in PD. These findings and their therapeutic relevance need to be further validated in PD patients without fall history, in early PD stages, and with various motor-motor dual-task challenges. PMID- 26997655 TI - Safety and efficacy of valproic acid treatment in SCA3/MJD patients. AB - BACKGROUND: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is one of 10 known polyglutamine (polyQ) diseases. In Drosophila and rat models of polyQ diseases, histone deacetylation (HDAC) inhibitors improved locomotor function and survival time by increasing histone acetylation levels and modulating gene expression. Valproic acid (VPA) is a pan-HDAC inhibitor used clinically to treat bipolar and seizure disorders. We evaluated the clinical safety and efficacy of VPA treatment for SCA3/MJD patients. METHODS: First, a randomized, open-label, dose-escalation method was used to evaluate tolerance to single-dose VPA administration in 12 SCA3/MJD patients. Patients were randomly assigned to three groups of four subjects, each with an oral dosage of 400 mg, 600 mg, or 800 mg (twice daily (bid) for one day). VPA was well-tolerated for one dose by all patient groups. Second, a randomized, double-blind, placebo controlled, dose-controlled study evaluated the safety and efficacy of multi-dose VPA (oral administration, twice daily (bid) for 12 weeks) in 36 SCA3/MJD patients. Patients received either low-dose VPA (800 mg/day), high-dose VPA (1200 mg/day), or placebo (n = 12 subjects per group). Symptoms were evaluated using the Scale for Assessment and Rating of Ataxia (SARA). RESULTS: Multi-dose VPA treatment improved SARA measures of locomotor function. Major adverse effects included dizziness and loss of appetite. CONCLUSIONS: VPA is a potentially beneficial agent for the treatment of SCA3/MJD. These results also provide insight into possible future therapeutics for polyQ diseases. PMID- 26997656 TI - Micrographia, much beyond the writer's hand. AB - INTRODUCTION: This review on micrographia aims to draw the clinician's attention to non-Parkinsonian etiologies, provide clues to differential diagnosis, and summarize current knowledge on the phenomenology, etiology, and mechanisms underlying micrographia. METHODS: A systematic review of the existing literature was performed. RESULTS: Micrographia, namely small sized handwriting has long been attributed to Parkinson's disease. However, it has often been observed as part of the clinical picture of additional neurodegenerative disorders, sometimes antedating the motor signs, or following focal basal ganglia lesions without any accompanying parkinsonism, suggesting that bradykinesia and rigidity are not sine qua-non for the development of this phenomenon. Therefore, micrographia in a patient with no signs of parkinsonism may prompt the clinician to perform imaging in order to exclude a focal basal ganglia lesion. Dopaminergic etiology in this and other cases is doubtful, since levodopa ameliorates letter stroke size only partially, and only in some patients. Parkinsonian handwriting is often characterized by lack of fluency, slowness, and less frequently by micrographia. Deviations from kinematic laws of motion that govern normal movement, including the lack of movement smoothness and inability to scale movement amplitude to the desired size, may reflect impairments in motion planning, possible loss of automaticity and reduced movement vigor. CONCLUSIONS: The etiology, neuroanatomy, mechanisms and models of micrographia are discussed. Dysfunction of the basal ganglia circuitry induced by neurodegeneration or disruption by focal damage give rise to micrographia. PMID- 26997657 TI - High-Yield Excited Triplet States in Pentacene Self-Assembled Monolayers on Gold Nanoparticles through Singlet Exciton Fission. AB - One of the major drawbacks of organic-dye-modified self-assembled monolayers on metal nanoparticles when employed for efficient use of light energy is the fact that singlet excited states on dye molecules can be easily deactivated by means of energy transfer to the metal surface. In this study, a series of 6,13 bis(triisopropylsilylethynyl)pentacene-alkanethiolate monolayer protected gold nanoparticles with different particle sizes and alkane chain lengths were successfully synthesized and were employed for the efficient generation of excited triplet states of the pentacene derivatives by singlet fission. Time resolved transient absorption measurements revealed the formation of excited triplet states in high yield (172+/-26 %) by suppressing energy transfer to the gold surface. PMID- 26997658 TI - Phase and amplitude of spontaneous retinal vein pulsations: An extended constant inflow and variable outflow model. AB - The constant inflow and variable outflow (CIVO) theory correctly predicts that spontaneous pulsation of the retinal veins will be visible close to the point where the vein exits the eye at the lamina cribrosa but will decrease rapidly in amplitude and become too small to see only a short distance upstream. However, the phase of vein oscillation relative to the oscillation of the intraocular pressure (IOP) predicted by CIVO has been unclear and controversial. We show that the CIVO model is indeterminate in predicting such phase relations. We propose a simple extension of the CIVO model that retains its basic equations but applies them to a larger domain that includes not only the intraocular (pre-laminar) portion of the vein but also the retrobulbar (post-laminar) portion of the vein behind the eye. We show that this extended CIVO model makes definite predictions about the phase of vein oscillation relative to the oscillation of IOP. This phase relationship is determined by the relative amplitude and phase of pulsations of the IOP and of the cerebrospinal fluid pressure (CSFP). If IOP and CSFP oscillate in phase, then the pre-laminar vein oscillates in phase with IOP when the amplitude of CSFP exceeds the amplitude of IOP but oscillates in counter phase with IOP when the amplitude of IOP exceeds that of CSFP. These relationships are modified when there is a phase difference between the oscillations of IOP and CSFP. When CSFP leads IOP, the phase of vein oscillation is advanced if the amplitude of CSFP exceeds that of IOP and is delayed if the amplitude of IOP exceeds that of CSFP. The result in each case is that maximum vein size occurs during the rising phase of IOP (ocular systole). We conclude that the driving force of vein oscillation is the difference between the oscillations of IOP and CSFP. The phase of this difference determines the phase relationships above. We show that additional delays in the phase of venous pulsation relative to that of IOP are induced by constriction of the vein within the lamina cribrosa and by recording the vein pulsations upstream from the lamina cribrosa. The amplitude of vein oscillation is proportional to the amplitude of the driving force and to the venous capacitance. Loss of spontaneous retinal vein pulsation with increase in mean CSFP is determined primarily by reduced venous capacitance. Increased amplitude of pulsation may occur when IOP is increased. It is the result of increased venous capacitance and possibly increased driving force of the pulsation. However, in chronic glaucoma the increase in capacitance may be counteracted by venous outflow obstruction, and the increase in driving force may be counteracted by reduced ocular blood flow. As a result retinal vein oscillation may be reduced in amplitude. PMID- 26997659 TI - Detecting small attractors of large Boolean networks by function-reduction-based strategy. AB - Boolean networks (BNs) are widely used to model gene regulatory networks and to design therapeutic intervention strategies to affect the long-term behaviour of systems. A central aim of Boolean-network analysis is to find attractors that correspond to various cellular states, such as cell types or the stage of cell differentiation. This problem is NP-hard and various algorithms have been used to tackle it with considerable success. The idea is that a singleton attractor corresponds to n consistent subsequences in the truth table. To find these subsequences, the authors gradually reduce the entire truth table of Boolean functions by extending a partial gene activity profile (GAP). Not only does this process delete inconsistent subsequences in truth tables, it also directly determines values for some nodes not extended, which means it can abandon the partial GAPs that cannot lead to an attractor as early as possible. The results of simulation show that the proposed algorithm can detect small attractors with length p = 4 in BNs of up to 200 nodes with average indegree K = 2. PMID- 26997660 TI - Transient response characteristics in a biomolecular integral controller. AB - The cellular behaviour of perfect adaptation is achieved through the use of an integral control element in the underlying biomolecular circuit. It is generally unclear how integral action affects the important aspect of transient response in these biomolecular systems, especially in light of the fact that it typically deteriorates the transient response in engineering contexts. To address this issue, the authors investigated the transient response in a computational model of a simple biomolecular integral control system involved in bacterial signalling. They find that the transient response can actually speed up as the integral gain parameter increases. On further analysis, they find that the underlying dynamics are composed of slow and fast modes and the speed-up of the transient response is because of the speed-up of the slow-mode dynamics. Finally, they note how an increase in the integral gain parameter also leads to a decrease in the amplitude of the transient response, consistent with the overall improvement in the transient response. These results should be useful in understanding the overall effect of integral action on system dynamics, particularly for biomolecular systems. PMID- 26997661 TI - Graph theory and stability analysis of protein complex interaction networks. AB - Protein complexes play an essential role in many biological processes. Complexes can interact with other complexes to form protein complex interaction network (PCIN) that involves in important cellular processes. There are relatively few studies on examining the interaction topology among protein complexes; and little is known about the stability of PCIN under perturbations. We employed graph theoretical approach to reveal hidden properties and features of four species PCINs. Two main issues are addressed, (i) the global and local network topological properties, and (ii) the stability of the networks under 12 types of perturbations. According to the topological parameter classification, we identified some critical protein complexes and validated that the topological analysis approach could provide meaningful biological interpretations of the protein complex systems. Through the Kolmogorov-Smimov test, we showed that local topological parameters are good indicators to characterise the structure of PCINs. We further demonstrated the effectiveness of the current approach by performing the scalability and data normalization tests. To measure the robustness of PCINs, we proposed to consider eight topological-based perturbations, which are specifically applicable in scenarios of targeted, sustained attacks. We found that the degree-based, betweenness-based and brokering-coefficient-based perturbations have the largest effect on network stability. PMID- 26997663 TI - Complex sources of variance in female dominance rank in a nepotistic society. AB - Many mammalian societies are structured by dominance hierarchies, and an individual's position within this hierarchy can influence reproduction, behaviour, physiology and health. In nepotistic hierarchies, which are common in cercopithecine primates and also seen in spotted hyaenas, Crocuta crocuta, adult daughters are expected to rank immediately below their mother, and in reverse age order (a phenomenon known as 'youngest ascendancy'). This pattern is well described, but few studies have systematically examined the frequency or causes of departures from the expected pattern. Using a longitudinal data set from a natural population of yellow baboons, Papio cynocephalus, we measured the influence of maternal kin, paternal kin and group size on female rank positions at two life history milestones, menarche and first live birth. At menarche, most females (73%) ranked adjacent to their family members (i.e. the female held an ordinal rank in consecutive order with other members of her maternal family); however, only 33% of females showed youngest ascendancy within their matriline at menarche. By the time they experienced their first live birth, many females had improved their dominance rank: 78% ranked adjacent to their family members and 49% showed youngest ascendancy within their matriline. The presence of mothers and maternal sisters exerted a powerful influence on rank outcomes. However, the presence of fathers, brothers and paternal siblings did not produce a clear effect on female dominance rank in our analyses, perhaps because females in our data set co-resided with variable numbers and types of paternal and male relatives. Our results also raise the possibility that female body size or competitive ability may influence dominance rank, even in this classically nepotistic species. In total, our analyses reveal that the predictors of dominance rank in nepotistic rank systems are much more complex than previously thought. PMID- 26997662 TI - Constrained inference of protein interaction networks for invadopodium formation in cancer. AB - Integrating prior molecular network knowledge into interpretation of new experimental data is routine practice in biology research. However, a dilemma for deciphering interactome using Bayes' rule is the demotion of novel interactions with low prior probabilities. Here the authors present constrained generalised logical network (CGLN) inference to predict novel interactions in dynamic networks, respecting previously known interactions and observed temporal coherence. It encodes prior interactions as probabilistic logic rules called local constraints, and forms global constraints using observed dynamic patterns. CGLN finds constraint-satisfying trajectories by solving a k-stops problem in the state space of dynamic networks and then reconstructs candidate networks. They benchmarked CGLN on randomly generated networks, and CGLN outperformed its alternatives when 50% or more interactions in a network are given as local constraints. CGLN is then applied to infer dynamic protein interaction networks regulating invadopodium formation in motile cancer cells. CGLN predicted 134 novel protein interactions for their involvement in invadopodium formation. The most frequently predicted interactions centre around focal adhesion kinase and tyrosine kinase substrate TKS4, and 14 interactions are supported by the literature in molecular contexts related to invadopodium formation. As an alternative to the Bayesian paradigm, the CGLN method offers constrained network inference without requiring prior probabilities and thus can promote novel interactions, consistent with the discovery process of scientific facts that are not yet in common beliefs. PMID- 26997664 TI - MOST HOMEOMORPHISMS WITH A FIXED POINT HAVE A CANTOR SET OF FIXED POINTS. AB - We show that, for any n ? 2, most orientation preserving homeomorphisms of the sphere S2n have a Cantor set of fixed points. In other words, the set of such homeomorphisms that do not have a Cantor set of fixed points is of the first Baire category within the set of all homeomorphisms. Similarly, most orientation reversing homeomorphisms of the sphere S2n+1 have a Cantor set of fixed points for any n ? 0. More generally, suppose that M is a compact manifold of dimension > 1 and ? 4 and H is an open set of homeomorphisms h : M -> M such that all elements of H have at least one fixed point. Then we show that most elements of H have a Cantor set of fixed points. PMID- 26997665 TI - Hints of a rotating spiral structure in the innermost regions around IRC +10216. AB - The Atacama Large Millimeter/submillimeter Array (ALMA) is allowing us to study the innermost regions of the circumstellar envelopes of evolved stars with un precedented precision and sensitivity. Key processes in the ejection of matter and dust from these objects occur in their inner zones. In this work, we present sub-arcsecond interferometric maps of transitions of metal-bearing molecules towards the prototypical C-rich evolved star IRC +10216. While Al-bearing molecules seem to be present as a roughly spherical shell, the molecular emission from the salts NaCl and KCl presents an elongation in the inner regions, with a central minimum. In order to accurately analyze the emission from the NaCl rotational lines, we present new calculations of the collisional rates for this molecule based on new spectroscopic constants. The most plausible interpretation for the spatial distribution of the salts is a spiral with a NaCl mass of 0.08M?. Alternatively, a torus of gas and dust would result in similar structures as those observed. From the torus scenario we derive a mass of ~ 1.1 * 10-4M?. In both cases, the spiral and the torus, the NaCl structure presents an inner minimum of 27 AU. In the case of the torus, the outer radius is 73 AU. The kinematics of both the spiral and the torus suggests that they are slowly expanding and rotating. Alternative explanations for the presence of the elongation are explored. The presence of these features only in KCl and NaCl might be a result of their comparatively high dipole moment with respect to the Al-bearing species. PMID- 26997667 TI - On Matrix-Valued Monge-Kantorovich Optimal Mass Transport. AB - We present a particular formulation of optimal transport for matrix-valued density functions. Our aim is to devise a geometry which is suitable for comparing power spectral densities of multivariable time series. More specifically, the value of a power spectral density at a given frequency, which in the matricial case encodes power as well as directionality, is thought of as a proxy for a "matrix-valued mass density." Optimal transport aims at establishing a natural metric in the space of such matrix-valued densities which takes into account differences between power across frequencies as well as misalignment of the corresponding principle axes. Thus, our transportation cost includes a cost of transference of power between frequencies together with a cost of rotating the principle directions of matrix densities. The two endpoint matrix-valued densities can be thought of as marginals of a joint matrix-valued density on a tensor product space. This joint density, very much as in the classical Monge Kantorovich setting, can be thought to specify the transportation plan. Contrary to the classical setting, the optimal transport plan for matrices is no longer supported on a thin zero-measure set. PMID- 26997668 TI - Resonance Energy of an Arene Hydrocarbon from Heat of Combustion Measurements. AB - A simple experimental method for determination of the resonance energy by measuring the energies of combustion for two isomeric compounds, aromatic 1-tert butyl-3,5-dimethylbenzene and nonaromatic trans,trans,cis-1,5,9-cyclododecatriene is proposed. Both compounds not only have the same molecular formula, but also contain the same number of sp2 and sp3 carbon atoms. After converting the obtained values into the gas phase heats of combustion and subtracting one value from another, the resulting mean resonance energy of 184 kJ/mol was obtained. The proposed method can be offered as an experiment for an undergraduate physical chemistry lab curriculum. PMID- 26997666 TI - Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG (S1-Level, AWMF Registry No. 015/050, December 2013). AB - Purpose: Official guideline coordinated and published by the German Society of Gynecology and Obstetrics (DGGG). Aim of the guideline was to standardize the diagnosis and treatment of patients with recurrent miscarriage (RM). Recommendations were proposed, based on the current national and international literature and the experience of the involved physicians. Consistent definitions, objective assessments and standardized therapy were applied. Methods: Members of the different involved societies developed a consensus in an informal process based on the current literature. The consensus was subsequently approved by the heads of the scientific societies. Recommendations: Recommendations for the diagnosis and treatment of patients with RM were compiled which took the importance of established risk factors such as chromosomal, anatomical, endocrine, hemostatic, psychological, infectious and immunological disorders into consideration. PMID- 26997669 TI - The root cause of the Supreme Court's decision legalizing homosexual "marriage". PMID- 26997670 TI - A hopeful response to Dr. van den Aardweg. PMID- 26997671 TI - In reply to Ms. Hosie. PMID- 26997672 TI - Response to Annmarie Hosie. PMID- 26997673 TI - Spiritual accompaniment for persons with same-sex attraction. PMID- 26997674 TI - Growing up with gay parents: What is the big deal? PMID- 26997675 TI - Transsexual attractions and sexual reassignment surgery: Risks and potential risks. AB - Transsexual issues and sexual reassignment surgery (SRS) are receiving a great deal of attention and support in the media, schools, and government. Given the early age at which youth seek treatment for transsexual attractions (TSA) and gender dysphoria and given the serious risks associated with such treatment, it is essential that family and youth be advised about these risks and alternative treatment options. Physicians and mental-health professionals have a professional responsibility to know and communicate the serious risks, in particular risk of suicide, that are associated with SRS; the spontaneous resolution of TSA in youth; the psychological conflicts that have been identified in such patients and in their parents; the successful treatment of conflicts associated TSA and the regrets of those who have been through SRS. SRS and gender theory are also viewed from the faith perspective of Pope Francis and Pope Emeritus Benedict XVI. Lay summary: Transsexuals and sex-change operations are receiving a great deal of attention. Young people may seek treatment for transsexual attractions at an early age even though these attractions may go away on their own. Psychological conflicts have been identified in these patients and their parents and may be successfully treated. There are serious risks associated with sex change. They include the risk of depressive illness and suicide. Physicians and mental-health professionals should know these risks and the regrets of those who have been through sex-change operations. These patients and their families also should be informed of other treatment options. PMID- 26997676 TI - Professional care for unwanted same-sex attraction: What does the research say? AB - In recent years, national and international medical and mental-health associations typically have emphasized the potential harmfulness of professional care for unwanted same-sex attraction (SSA or homosexuality) and behavior. State legislatures in the US and legislative bodies in other countries either have passed or are considering passing laws which would penalize professionals who provide professional care for unwanted SSA-to minors and/or adults-including the loss of the license to practice. This paper was written as a response to the present situation in the UK. The paper reviews the universal ethics of all medical and mental-health professionals to avoid harm and do good (non maleficence/non-malfeasance and beneficence); discusses the documented potential for harm when using every mental-health treatment for every presenting problem; clarifies steps taken by the Alliance for Therapeutic Choice and Scientific Integrity (Alliance), its clinical and research divisions, the National Association for Research and Therapy of Homosexuality Institute (NARTH Institute) and its international division, the International Federation for Therapeutic Choice (IFTC), to promote ethical professional care for unwanted SSA; clarifies the injustice and presumed ideological biases of the medical and mental-health associations' warning about the potential for harm for psychotherapy only for unwanted SSA and not all psychotherapy approaches; and documents that the research purporting to show this harmfulness, in the research authors own words, does not do so. Recommendations to promote scientific integrity in the conduct and reporting of relevant research are offered. Lay Summary: There has been a lot of controversy about the potential harmfulness of professional care for unwanted same-sex attraction and behavior (SSA or homosexuality). This paper reviews the ethics of all medical and mental health professionals to avoid harm and do good; discusses the known potential for harm when using any mental health treatment for any problem; clarifies steps taken to promote ethical professional care for unwanted SSA; notes the injustice and possible biases of those who warn about the potential for harm of psychotherapy for unwanted SSA; and documents that the research said to show this harmfulness, in the research authors own words, does not do so. PMID- 26997677 TI - Homosexuality and scientific evidence: On suspect anecdotes, antiquated data, and broad generalizations. AB - The American Psychiatric Association and the American Psychological Association have suggested for many years now that there is significant empirical evidence supporting the claim that homosexuality is a normal variant of human sexual orientation as opposed to a mental disorder. This paper summarizes and analyzes that purported scientific evidence and explains that much (if not all) of the evidence is irrelevant and does not support the homosexuality-is-not-a-mental disorder claim. As a result of their deficiencies and arbitrariness, the credibility those two groups that are typically deemed authoritative and trustworthy is called into question. Lay summary: At one time, homosexuality was considered to be mentally disordered. Since the 1970s, however, major medical associations in the U.S. have labeled homosexuality as a normal counterpart of heterosexuality. Those medical associations have proposed that their homosexuality-is-normal claim is based on "scientific evidence." This article critically reviews that "scientific evidence" and finds that much of their literature does not support the claim that homosexuality is normal. This article suggests that instead of supporting their claim with scientific evidence, those major medical associations arbitrarily label homosexuality as normal. PMID- 26997678 TI - A response to the Academy of Science of South Africa's Diversity in Human Sexuality Report. PMID- 26997679 TI - The abundance of 28Si32S, 29Si32S, 28Si34S, and 30Si32S in the inner layers of the envelope of IRC+10216. AB - We present high spectral resolution mid-IR observations of SiS towards the C-rich AGB star IRC+10216 carried out with the Texas Echelon-cross-Echelle Spectrograph mounted on the NASA Infrared Telescope Facility. We have identified 204 ro vibrational lines of 28Si32S, 26 of 29Si32S, 20 of 28Si34S, and 15 of 30Si32S in the frequency range 720 - 790 cm-1. These lines belong to bands v = 1 - 0, 2 - 1, 3 - 2, 4-3, and 5-4, and involve rotational levels with Jlow ? 90. About 30 per cent of these lines are unblended or weakly blended and can be partially or entirely fitted with a code developed to model the mid-IR emission of a spherically symmetric circumstellar envelope composed of expanding gas and dust. The observed lines trace the envelope at distances to the star ? 35R?(? 0".7). The fits are compatible with an expansion velocity of 1+2.5(r/R? -1) km s-1 between 1 and 5R?, 11 km s-1 between 5 and 20R?, and 14.5 km s-1 outwards. The derived abundance profile of 28Si32S with respect to H2 is 4.9 * 10-6 between the stellar photosphere and 5R?, decreasing linearly down to 1.6 * 10-6 at 20R? and to 1.3 * 10-6 at 50R?. 28Si32S seems to be rotationally under LTE in the region of the envelope probed with our observations and vibrationally out of LTE in most of it. There is a red-shifted emission excess in the 28Si32S lines of band v = 1 0 that cannot be found in the lines of bands v = 2 - 1, 3 - 2, 4 - 3, and 5 - 4. This excess could be explained by an enhancement of the vibrational temperature around 20R? behind the star. The derived isotopic ratios 28Si/29Si, and 32S/34S are 17 and 14, compatible with previous estimates. PMID- 26997681 TI - DNA based association and description of the larval stage of Drusus melanchaetes McLachlan, 1876 (Trichoptera: Limnephilidae: Drusinae) with notes on ecology and zoogeography. AB - At three alpine locations in Switzerland adults of Drusus melanchaetes and unknown Drusinae larvae which could not be identified with existing keys were sampled. Based on DNA association with adults, we identified the unknown larvae as D. melanchaetes. To further support the association of specimens a phylogeny was estimated with the putative closest relatives of D. melanchaetes - D. monticola and D. nigrescens - and five other species of Drusus (D. chrysotus, destitutus, discolor, muelleri and romanicus). A highly supported monophyletic clade groups unknown larvae and D. melanchaetes specimens from the central Alps and Austria (Vorarlberg), confirming the association. Based on morphology, larvae of Drusus melanchaetes key out together with D. destitutus in existing keys. D. melanchaetes is separated from the latter species by the shape of the lateral head profile which is almost straight and shows a small step at the height of the antenna, whereas in D. destitutus the lateral head profile is evenly rounded. In addition, in frontal view, the shape of the lateral head outline is straight in D. melanchaetes and rounded in D. destititus. There are also differences in the shape of the pronotum and in the number of the posterodorsal setae at the eighth abdominal dorsum. PMID- 26997680 TI - The Role of Sexual Orientation in School-Based Victimization: A Meta-Analysis. AB - School-based victimization is associated with poorer developmental, academic, and health outcomes. This meta-analytic review compared the mean levels of school based victimization experienced by sexual minority youth to those of heterosexual youth, and examined moderators of this difference. Results from 18 independent studies (N = 56,752 participants) suggest that sexual minority youth experience moderately higher levels of school-based victimization compared to heterosexual youth (d = .33). This effect varied by two study characteristics: the average effect size increased over time and was larger in studies that had a greater proportion of male participants. Results highlight the need for future research on school-based victimization to include measures of sexual orientation and for interventions to include a component that addresses sexual orientation. PMID- 26997682 TI - The Hidden Work of Exiting Homelessness: Challenges of Housing Service Use and Strategies of Service Recipients. AB - This study explored the experiences of parents attempting to re-attain housing after a shelter stay. Eighty parents participated in semistructured face-to-face interviews approximately six months after being recruited from shelters in four states across the U.S. Qualitative analyses identified common challenges of service use, strategies of service recipients, and characteristics of positive and negative service experiences. Challenges of service use included "catch-22s" resulting from incongruity between service policies/procedures and participants' contexts and/or requirements of other services, confusion and uncertainty resulting from absent or insufficient communication about services, and long waitlists. Participants demonstrated persistence and determination, networked with service providers, and activated formal resources. Positive service experiences were tailored to families' needs and marked by clear and consistent communication between providers and with service recipients. Findings suggest effective health communication tactics should be applied to housing services. Providers should collaborate to ensure service attainment does not impede other pathways to stability. PMID- 26997683 TI - Understanding the Attainment of Stable Housing: A Seven-Year Longitudinal Analysis of Homeless Adolescents. AB - Stable housing provides a solid foundation for youth development, making it an essential topic of study among young homeless people. Although gains have been made in research with adolescents and young adults experiencing homelessness, few longitudinal studies of this population exist, clouding the long-term housing outcome picture. The current study examined the course and risk factors for homelessness in a sample of 243 homeless adolescents followed over a seven-year period. The vast majority of youth returned to stable housing quickly; however, early experiences of homelessness, even at this young age, were observed to have a substantial negative impact on future housing. Participants from poorer neighborhoods and those identifying as ethnic minorities also took longer to achieve stable housing. The data suggest that family reunification interventions may serve this population well. Preparing youth for returning home may prevent subsequent homeless episodes, while also improving their overall functioning. PMID- 26997684 TI - Bayesian T-optimal discriminating designs. AB - The problem of constructing Bayesian optimal discriminating designs for a class of regression models with respect to the T-optimality criterion introduced by Atkinson and Fedorov (1975a) is considered. It is demonstrated that the discretization of the integral with respect to the prior distribution leads to locally T-optimal discriminating design problems with a large number of model comparisons. Current methodology for the numerical construction of discrimination designs can only deal with a few comparisons, but the discretization of the Bayesian prior easily yields to discrimination design problems for more than 100 competing models. A new efficient method is developed to deal with problems of this type. It combines some features of the classical exchange type algorithm with the gradient methods. Convergence is proved and it is demonstrated that the new method can find Bayesian optimal discriminating designs in situations where all currently available procedures fail. PMID- 26997685 TI - The Home-Based Occupational Therapy Intervention in the Alzheimer's Disease Multiple Intervention Trial (ADMIT). AB - There is no way to prevent functional declines related to Alzheimer's Disease (AD). The use of occupational therapy (OT) has been shown to be successful in managing some aspects of AD. We added home-based OT to evidence-based best practice for AD with the aim of delaying functional decline in people with AD. OT was delivered in the home to a caregiver dyad including the person with AD and her/his caregiver. This paper describes the OT intervention for the AD Multiple Intervention Trial, a parallel randomized controlled trial. We include baseline data on the 180 caregiver dyads. PMID- 26997687 TI - The larva and life cycle of Annitella apfelbecki Klapalek, 1899, including a redescription of Melampophylax nepos McLachlan, 1880 (Trichoptera: Limnephilidae). AB - The hitherto unknown larva of Annitella apfelbecki (Klapalek, 1899) is described and discussed in the context of contemporary Limnephilidae keys. In addition, its life cycle is discussed, and zoogeographical and ecological notes are included. Finally, we provide some additional information on the morphologically very similar larva of Melampophylax nepos (McLachlan, 1880). PMID- 26997686 TI - Self-Regulatory Strategies in Daily Life: Selection, Optimization, and Compensation and Everyday Memory Problems. AB - The effective use of self-regulatory strategies, such as selection, optimization, and compensation (SOC) requires resources. However, it is theorized that SOC use is most advantageous for those experiencing losses and diminishing resources. The present study explored this seeming paradox within the context of limitations or constraints due to aging, low cognitive resources, and daily stress in relation to everyday memory problems. We examined whether SOC usage varied by age and level of constraints, and if the relationship between resources and memory problems was mitigated by SOC usage. A daily diary paradigm was used to explore day-to-day fluctuations in these relationships. Participants (n=145, ages 22 to 94) completed a baseline interview and a daily diary for seven consecutive days. Multilevel models examined between- and within-person relationships between daily SOC use, daily stressors, cognitive resources, and everyday memory problems. Middle-aged adults had the highest SOC usage, although older adults also showed high SOC use if they had high cognitive resources. More SOC strategies were used on high stress compared to low stress days. Moreover, the relationship between daily stress and memory problems was buffered by daily SOC use, such that on high stress days, those who used more SOC strategies reported fewer memory problems than participants who used fewer SOC strategies. The paradox of resources and SOC use can be qualified by the type of resource-limitation. Deficits in global resources were not tied to SOC usage or benefits. Conversely, under daily constraints tied to stress, the use of SOC increased and led to fewer memory problems. PMID- 26997688 TI - What childhood characteristics predict psychological resilience to economic shocks in adulthood? AB - This paper investigates whether people's psychological resilience to one of the most important economic shocks - job loss - can be predicted using early childhood characteristics. Using a longitudinal data that tracked almost 3000 children into adulthood, we showed that the negative effect of unemployment on mental well-being and life satisfaction is significantly larger for workers who, as adolescents, had a relatively poor father-child relationship. Maternal unemployment, on the other hand, is a good predictor of how individuals react psychologically to future unemployment. Although the results should be viewed as illustrative and more research is needed, the current article provides new longitudinal evidence that psychological resilience to job loss may be determined early on in the life cycle. PMID- 26997689 TI - The Individualized Quality Control Plan - Coming Soon to Clinical Microbiology Laboratories Everywhere! AB - As of January 1, 2016, microbiology laboratories can choose to adopt a new quality control option, the Individualized Quality Control Plan (IQCP), under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). This voluntary approach increases flexibility for meeting regulatory requirements and provides laboratories the opportunity to customize QC for their testing in their unique environments and by their testing personnel. IQCP is an all-inclusive approach to quality based on risk management to address potential errors in the total testing process. It includes three main steps, (1) performing a risk assessment, (2) developing a QC plan, and (3) monitoring the plan through quality assessment. Resources are available from the Centers for Medicare & Medicaid Services, Centers for Disease Control and Prevention, American Society for Microbiology, Clinical and Laboratory Standards Institute, and accrediting organizations, such as the College of American Pathologists and Joint Commission, to assist microbiology laboratories implementing IQCP. PMID- 26997690 TI - At the margins: Agriculture, subsidies and the shifting fate of North America's Native Grassland. AB - We examined patterns of shifting cropland cultivation in the US Great Plains from the dust bowl to the beginning of the 21st century, by comparing land-cover data from 400 sample sites across the region from the 1930s, 1950s, 1970s and, 1990s and 2000s. We argue that understanding the use of marginal land for cultivation in the Great Plains since the Great Depression requires understanding the interacting dynamics of demography, technology, and policy. The small area land cover data are nested within 50 target counties across the region. We draw on these dynamics, and their interactions with a range of policy programs aimed at reducing environmental impacts of agriculture, to tell the story of how and when marginal lands have been brought into use. In a multi-level panel design, macro- and micro-level covariates were used to predict levels of encroachment on marginal soils. We conclude that land retirement programs (like the Conservation Reserve Program) have had a generally stabilizing effect on the micro-level patterns of land use in recent decades, but that increased levels of encroachment on marginal soils and native grassland remain a problem in areas with higher or increasing population densities. PMID- 26997691 TI - Cytotoxic and Antitumour Studies of Acetoacetanilide N(4) methyl(phenyl)thiosemicarbazone and its Transition Metal Complexes. AB - Cytotoxic activities of acetoacetanilide N(4)-methyl(phenyl)thiosemicarbazone (L2H) and its seven different metal complexes were studied. Of these, IC50 value of the copper complex was found to be 46 MUg/ml. Antitumour studies of this copper complex was carried out using Daltons Lymphoma Ascites cell-induced solid tumour model and Ehrlich's Ascites Carcinoma cell-induced ascites tumour model. Administration of the copper complex at different concentrations (10, 5 and 1 mg/kg b. wt) inhibited the solid tumour development in mice and increased the mean survival rate and the life span of Ascites tumour bearing mice in a concentration dependent manner. PMID- 26997692 TI - Flavonoids, Antioxidant Activity and Aroma Compounds Analysis from Different Kinds of Tartary Buckwheat Tea. AB - The rutin, quercetin concentrations, antioxidant activity, and aroma compounds in different commercial tartary buckwheat tea were analyzed in our study. Results revealed that the materials and the processing protocol affected the chemical composition and activity of tartary buckwheat tea. Rutin and quercetin concentrations, antioxidant activity were significantly different in various kinds of tartary buckwheat tea, where the whole bran tea and the whole plant tea had the lower rutin, but higher quercetin concentrations and higher antioxidant activity. The whole embryo tea had the converse results. There was strong correlation between quercetin concentration and antioxidant activity (r>0.98, P<0.05). Meanwhile, Twenty eight different aroma compounds in tartary buckwheat tea were identified by gas chromatography-mass spectrometry. Those compounds were mainly composed of pyrazine, aldehydes, fatty acids and ketones. The main type of aroma compounds in different tartary buckwheat tea were similar, but their relative contents were different. The implications to the quality control of buckwheat tea were extensively discussed. PMID- 26997693 TI - In vitro Screening for Antioxidant, Antimicrobial, and Antidiabetic Properties of Some Korean Native Plants on Mt. Halla, Jeju Island. AB - In this study, Prunus padus, Lonicera caerulea, Berberis amurensis, and Ribes maximowiczianum, which are mainly distributed on Mt. Halla, Jeju Island, have been investigated for their antioxidant, antimicrobial, and antidiabetic activities. The methanol extracts of R. maximowiczianum leaves and P. padus branches exhibited significant and dose-dependent antioxidant activity including electron-donation ability and reducing power. To analyze the antimicrobial activity, each extract was tested by a serial two-fold dilution method against five selected gram-positive bacteria and four gram-negative bacteria, and this suggested that P. padus branches possessed the maximum antimicrobial activity against most of the gram-positive bacteria tested. In addition, the methanol extracts of P. padus branches exhibited the highest alpha-glucosidase inhibitory activity with an IC50 value of 1.0+/-0.1 MUg/ml, indicating that P. padus is a promising source as a herbal medicine. PMID- 26997694 TI - Fabrication and Characterization of Sertaconazole Nitrate Microsponge as a Topical Drug Delivery System. AB - Present study was taken up to develop a topical formulation that releases the drug in controlled manner, reduce the side effects associated with topical drug delivery and improve product efficacy with aid of microsponges. Microsponges loaded with sertaconazole nitrate were prepared by using quasi emulsion solvent diffusion with five different proportions of the polymer (Eudragit RS 100). The developed microsponges were analyzed for particle size, production yield, entrapment efficiency and drug content. Scanning electron microscopic images of microsponges revealed that they are spherical in shape and contain pores. Pore structure analysis was done by using mercury intrusion porosimetry technique, which confirmed the porous nature of microsponges. Microsponges were then incorporated in to a 1% corbopol gel and evaluated for pH, drug content, texture profile analysis and in vitro drug release. The batch F IV was found to be optimal as it shown 69.38% controlled drug release in 8 h that followed Higuchi model. PMID- 26997695 TI - Prenatal Exposure to Silver Nanoparticles Causes Depression Like Responses in Mice. AB - Despite increasing studies on silver nanoparticles, their mechanism of action is not so clear, especially their probable toxicity on reproduction procedure, developmental process and offspring behavior. Therefore in the present study the effect of silver nanoparticles exposure during gestational period on offspring's depression behavior was assessed. Thirty virgin female mice were divided into three groups (n=10 for each group) including: one control and two experimental groups, which received an equal volume (0.2 ml) of suspension containing 0, 0.2 and 2 mg/kg of silver nanoparticles, respectively. After mating, the suspension was injected and repeated every 3 days till accouchement. Depression behaviors were assessed by tail suspension test and forced swimming test, in 45-day-old male and female progenies (6 groups, n=10). In males, both dose of silver nanoparticles (0.2 and 2 mg/kg) decreased mobility and increased immobility time in forced swimming test (P<0.05), but in female no effects were observed in mobility and immobility time. In tail suspension test, 2 mg/kg of silver nanoparticles lead to decrease of mobility time (P<0.05) and increase of immobility time (P<0.05) in female offspring but in males no significant effect was observed on mobility and immobility time. We may concluded that the prenatal exposure to silver nanoparticles probably cause gender-specific depression like behaviors in offspring, possibly through neurotoxic effect during neuronal development. PMID- 26997696 TI - Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital. AB - Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy. PMID- 26997697 TI - Comparison of Calcium Phosphate and Zinc Oxide Nanoparticles as Dermal Penetration Enhancers for Albumin. AB - Dermal drug delivery is highly preferred by patients due to its several advantages. Protein therapeutics have attracted huge attention recently. Since dermal delivery of proteins encounter problems, in this investigation, zinc oxide nanoparticles and calcium phosphate nanoparticles were compared as enhancers for dermal permeation of albumin. Albumin was applied simultaneously with zinc oxide nanoparticles or calcium phosphate nanoparticles on pieces of mouse skin. Skin permeation of albumin over time was determined using a diffusion cell. Skin distribution of the nanoparticles and albumin over time was determined by optical and fluorescence microscopy. Zinc oxide nanoparticles and calcium phosphate nanoparticles acted as enhancers for skin permeation of albumin. Cumulative permeated albumin in presence of zinc oxide nanoparticles after 0, 0.5, 1, 1.5 and 2 h, were 0+/-0, 11.7+/-3.3, 21.1+/-3.5, 40.2+/-3.6 and 40.2+/-3.6 mg, respectively and in presence of calcium phosphate nanoparticles were 0+/-0, 20.9+/-7.4, 33.8+/-5.5, 33.8+/-3.7 and 33.8+/-3.7 mg, respectively. After 0.5 h, little amount of albumin was permeated in presence of every kind of the nanoparticles. After 0.5 or 1 h, the permeated albumin in presence of calcium phosphate nanoparticles was more than that in presence of zinc oxide nanoparticles and after 1.5 h the permeated albumin in presence of zinc oxide nanoparticles was more than that in presence of calcium phosphate nanoparticles. Images of skin distribution of the two nanoparticles over time, were somewhat different and distribution of albumin correlated with the distribution of the nanoparticles alone. The profiles of albumin permeation (in presence of each of the nanoparticles) versus time was delayed and linear for both nanoparticles while the slope for calcium phosphate nanoparticles was higher than zinc oxide nanoparticles. The enhancer effect of zinc oxide nanoparticles was stronger while the enhancer effect of calcium phosphate nanoparticles was quicker. Maximum cumulative (total) permeated albumin in presence of zinc oxide nanoparticles was obtained at time of 1.5 h, which was 40.2+/-3.6 mg, while in presence of calcium phosphate nanoparticles, it was obtained at 1 h, which was 33.8+/-5.5 mg. Skin distribution of the nanoparticles and albumin confirmed the above profiles. PMID- 26997698 TI - Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets. AB - Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID- 26997700 TI - Quality by Design Approach for Simultaneous Estimation of Doxycycline Hyclate and Curcumin by RP-HPLC Method. AB - A simple, rapid, reliable, robust and optimized reversed phase high performance liquid chromatographic method for simultaneous estimation of doxycycline hyclate and curcumin was successfully developed and validated as per International Conference on Harmonization guidelines. The objective was achieved in terms of well separated peaks within 10 min on a Waters Sunfire C8 column with dimensions of 250*4.6 mm, particle size 5.0 MUm using mobile phase consisting of 30 volumes of potassium dihydrogen phosphate buffer (50 mM) adjusted to pH 6.5+/-0.1 with triethylamine and 70 volumes of methanol at flow rate of 0.85 ml/min. The column effluents were monitored at 400 nm maintained at ambient column temperature (28(o)). The developed method was found linear over the concentration range of 200-700 MUg/ml for doxycycline hyclate and 8-28 MUg/ml for curcumin, the detection and quantitation limit was found to be 26.063 and 78.97 MUg/ml for doxycycline hyclate; 0.795 and 2.13 MUg/ml for curcumin, respectively. The developed method was optimized using Minitab software version 16 to meet the current quality by design requirements. The method validation was done for linearity, range, detection and quantitation limit, accuracy, precision, specificity, system suitability testing, and robustness. PMID- 26997699 TI - Quality Assessment of Psoralea fructus by HPLC Fingerprint Coupled with Multi components Analysis. AB - Psoralea Fructus, the dried and ripe fruit of Psoralea corylifolia L., have been used as traditional medicine. There is substantial evidence that multiple constituents are responsible for the beneficial effects of this medicine. To effectively control the quality of this herbal medicine, HPLC fingerprint analysis was performed on a SinoChrom ODS-BP column with mobile phase of a gradient prepared from H2O and CH3CN, which the conditions used for gradient elution were: 0-10 min, 5-45% CH3CN; 10-45 min, 45-70% CH3CN; 45-50 min, 70-100% CH3CN; 50-60 min, 100-100% CH3CN, and the flow rate was 1.0 ml/min. It was obtained on the basis of the chromatographic data from 28 batches of samples, which contained 26 common peaks and 13 peaks were identified by the electrospray ionization-mass spectrometry as psoralen, isopsoralen, isobavachin, neobavaisoflavone, bavachin, corylin, broussochalcone B, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone and backuchiol. The contents of these 13 compounds were also simultaneously examined. By using principal component analysis, 28 batches of samples collected from 6 producing locations with different collecting time were evaluated and differentiated. In summary, the data as described in this study offer valuable information for quality control and proper use of Psoralea Fructus. PMID- 26997701 TI - Physicochemical and Antioxidant Assays of Methanol and Hydromethanol Extract of Ariel Parts of Indigofera tinctoria Linn. AB - Free radicals or reactive oxygen indices give rise to oxidative injury, which is a fundamental mechanism underlying a number of disease like diabetes, cancer, neurodegenerative disorders. Deleterious effects of reactive oxygen species can be nullified by using different natural antioxidants derived from plants Indigofera tinctoria is such plant. This study was planned in order to trace and determine the antioxidant capability of Indigofera tinctoria. All the reagents and chemicals used in this study were obtained from reliable firms. The plant extracts were subjected to phytochemical screening, quantitative assays and antioxidant profiling. The results suggested that plant extracts contained all pharmacologically important phytoconstituents in appreciable amounts and having excellent antioxidant capabilities. PMID- 26997702 TI - Effect of Structural Changes in Proteins Derived from GATA4 Nonsynonymous Single Nucleotide Polymorphisms in Congenital Heart Disease. AB - Congenital heart disease is the most common type of birth defect. The single nucleotide polymorphism in GATA4 is associated with various congenital heart disease phenotypes. In the present study, we analysed the nonsynonymous single nucleotide polymorphism of GATA4, which are involved in congenital heart disease by predicting the changes in protein structures. Total of 49 nonsynonymous single nucleotide polymorphisms of GATA4 was screened from congenital heart disease patients of Mysore and also globally reported nonsynonymous single nucleotide polymorphisms. To understand the role of nonsynonymous single nucleotide polymorphisms, we mutated the sequence and translated into amino acids. Further the mutated protein secondary structure is predicted and tertiary structure is predicted using homology modeling. The quantitative evaluation of protein structure quality was verified with Volume Area Dihedral Angle Reporter server. Results revealed the secondary, tertiary structural changes along with changes in free energy of folding, volume and accessible surface area. Thus, the structural changes in the mutated proteins impaired the normal function of GATA4. PMID- 26997703 TI - Development of Validated Bioanalytical HPLC-UV Method for Simultaneous Estimation of Amlodipine and Atorvastatin in Rat Plasma. AB - A simple, economical and robust analytical high-performance liquid chromatography ultraviolet method was developed and validated for simultaneous chromatographic elution of two cardiovascular drugs viz. amlodipine and atorvastatin in biological fluid for the first time. Only two liquid chromatography-mass spectrometry/mass spectrometry methods are available in literature for quantitation of selected pair of analytes. The bioanalytical method was developed in rat plasma by using Thermo beta-basic C18 (100*4.6 mm, 5 MUm) and mobile phase was composed of dibasic phosphate buffer (pH 3.0):acetonitrile in the ratio of 55:45 at a flow rate of 1 ml/min with ultraviolet detection monitored at 240 nm. The selected chromatographic conditions were found to effectively separate amlodipine (5.1 min) and atorvastatin (12.1 min). The parametric statistics,i.e. correlation coefficient of 0.999, was assessed for both the drugs having linearity over the tested concentration range (0.05 to 10.0 MUg/ml) in rat plasma using an unweighted calibration curve. The mean recovery (%) was more than 92.8% for both the drugs using protein precipitation method. The accuracy of samples for six replicate measurements at lower limit of quantitation level was within limit. The method was validated and was successfully applied to the nonclinical pharmacokinetic study of combination tablets containing amlodipine and atorvastatin in six Sprague Dawley rats. PMID- 26997704 TI - Analytical Quality by Design Approach in RP-HPLC Method Development for the Assay of Etofenamate in Dosage Forms. AB - By considering the current regulatory requirement for an analytical method development, a reversed phase high performance liquid chromatographic method for routine analysis of etofenamate in dosage form has been optimized using analytical quality by design approach. Unlike routine approach, the present study was initiated with understanding of quality target product profile, analytical target profile and risk assessment for method variables that affect the method response. A liquid chromatography system equipped with a C18 column (250*4.6 mm, 5 MU), a binary pump and photodiode array detector were used in this work. The experiments were conducted based on plan by central composite design, which could save time, reagents and other resources. Sigma Tech software was used to plan and analyses the experimental observations and obtain quadratic process model. The process model was used for predictive solution for retention time. The predicted data from contour diagram for retention time were verified actually and it satisfied with actual experimental data. The optimized method was achieved at 1.2 ml/min flow rate of using mobile phase composition of methanol and 0.2% triethylamine in water at 85:15, % v/v, pH adjusted to 6.5. The method was validated and verified for targeted method performances, robustness and system suitability during method transfer. PMID- 26997705 TI - Screening and Toxicity Analysis of Catechin Isomers Against FemA Protein. AB - Fem proteins are the essential structural proteins of various gram-positive bacteria. These are of three different types namely FemX (FmhB), FemA and FemB. Only two Fem protein crystallographic structures are available till date, one for FemA in Staphylococcus aureus and another for FemX in Weissella viridescensis. In this study, computational methods are used to evaluate interaction of FemA protein with catechin and epicatechin analogues. The interaction of FemA protein with catechin and epicatechin analogues are confirmed by binding energy and scores given by Autodock Vina and UCSF Dock docking softwares, which is followed by Lipinski filters and toxicity studies using online Lipinski server of SCFBIO and OSIRIS. Catechin gallate has been found as the best ligand for FemA protein in all aspects and it has outperformed all catechin and epicatechin isomers. PMID- 26997706 TI - Formulation of Thermosensitive in situ Otic Gel for Topical Management of Otitis Media. AB - Antibiotics and antiinflammatory agents are the primary and main therapeutic categories in the treatment of otitis media. One of the simpler and feasible approaches of minimizing the problem of repeated use and subsequent resistance is development of sustained release formulation. Therefore, the present investigation aimed to develop a sustained release in situ gel formulation containing combination of broad spectrum antibiotic and antiinflammatory agents for the management of otits media. The prolonged release is achieved by phase transition of Poloxamer 407 (in situ) from sol to gel at a physiological temperature in combination with viscosity imparting agent Natrasol 250 and Klucel HF. The formulation P3N3 (19% w/v Poloxamer 407, 1.5% w/v Natrasol 250) and P3K3 (19% w/v Poloxamer 407, 1.5% w/v Klucel HF) showed mucoadhesive strength 37.17+/ 0.32*10(3) and 38.12+/-0.13*10(3) dyne/cm(2), respectively, and gel strength 2.1 and 2 cm, respectively. Both these formulations indicated good drug content and viscosity besides a good gelling ability. The in vitro diffusion has demonstrated prolongation of release of both the drugs over a period of 8 h. PMID- 26997708 TI - Antioxidant Studies on Ethanol Extracts from Two Selected Genera of Indian Lamiaceae. AB - The present work is targeted to evaluate antioxidant activity of ethanol extracts from the leaves of Plectranthus mollis and Salvia officinalis belonging to family Lamiaceae using nitric oxide scavenging, hydrogen peroxide scavenging, ferric reducing antioxidant power assay and lipid peroxidation methods. The results of the study indicate that the leaf extracts of both the plants possess in vitro antioxidant activity. The higher amount of flavanoids and phenolic compounds may correspond to their greater antioxidant activity. PMID- 26997707 TI - Antipsychotic Trials in Schizophrenia from India: A Systematic Review and Meta analysis. AB - Ethnic and regional variations have been found in the pharmacological treatment response. Though many efficacy studies have been conducted in India for antipsychotic treatment modalities of schizophrenia, there is a lack meta analytic data of the existing literature from India. This study aimed to conduct a systematic review and meta-analysis of the antipsychotic treatment trials of schizophrenia in the Indian context. All controlled trials from India evaluating the clinical efficacy of antipsychotics in patients with schizophrenia were evaluated and 28 trials were included in the metanalysis. Effect sizes were computed using Cohen's 'd' and risk of bias was evaluated. Meta analysis revealed superiority of first generation antipsychotics over placebo (mean effect size of 1.387, confidence interval of 1.127 to 1.648). Second generation antipsychotics were marginally better than first generation antipsychotics (effect size 0.106, confidence intervals 0.009 to 0.204). There was improvement in the methodology of the trials over time (Kendall tau=0.289, P=0.049), though no statistically significant increase in trial duration and sample size was noted. There is lack of data on long term efficacy of antipsychotic in schizophrenia from India. First generation antipsychotics have demonstrated benefits over placebo in patients with schizophrenia in the Indian context, though marginally lesser than second generation ones. PMID- 26997709 TI - Simultaneous Estimation of Aloe Emodin and Emodin from Rheum emodi, Cassia alata and Aloes by HPTLC. AB - A simple, precise, specific, accurate high performance thin layer chromatography method was developed for simultaneous estimation of aloe emodin and emodin from medicinal plants like Rheum emodi (Rhubarb), Barbados aloes (dried juice of Aloe barbadensis leaf) and Cassia alata (Candle bush). Thin layer chromatographic aluminum plates pre-coated with silica gel 60 F254 was used as the stationary phase for chromatographic separation of the drugs. Toluene:ethyl acetate:formic acid (10:2:1 v/v/v) was selected as mobile phase and analysis was carried out in absorbance mode at iso-absorptive wavelength of 263 nm. This method shows good resolution for both drugs with retention factor 0.37+/-0.03 and 0.55+/-0.03 for aloe emodin and emodin, respectively. The regression analysis data indicated good linear relationship for the calibration plots for aloe emodin and emodin in the range of 300 - 800 ng/spot and 150 - 400 ng/spot and regression coefficient was 0.9993 and 0.9994, respectively. Validation of the method was performed according to International Conference on Harmonisation guidelines for following parameters: Accuracy, precision, limit of detection, linearity, limit of quantification, robustness and specificity. In conclusion, the developed method was found to be rapid, simple, reliable and specific for the identification and quantitation of these anthraquinones in medicinal plants and marketed formulations. PMID- 26997710 TI - In vitro Antibacterial Activity of Aqueous and Ethanol Extracts of Aristolochia indica and Toddalia asiatica Against Multidrug-Resistant Bacteria. AB - Bacteria have developed multidrug resistance against available antimicrobial agents. Infectious diseases caused by these multidrug-resistant bacteria are major causes of morbidity and mortality in human beings. Synthetic drugs are expensive and inadequate for the treatment of diseases, causing side effects and ineffective against multidrug-resistant bacteria. The medicinal plants are promising to have effective antimicrobial property due to presence of phytochemical compounds like alkaloids, flavanoids, tannins and phenolic compounds. The present study aimed to find the antimicrobial activity of medicinal plants against multidrug-resistant bacteria. Multidrug-resistant bacteria were identified by Kirby-Bauer disc diffusion method. Production of beta lactamases (extended spectrum beta-lactamases, metallo beta-lactamase and AmpC beta-lactamase) were identified by combination disc method. Antibacterial activity of aqueous and ethanol extract of Aristolochia indica and Toddalia asiatica were detected by agar well diffusion assay and minimum inhibitory concentration. All bacteria used in this study showed antibiotic resistance to >=3 antibiotics. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Vibrio cholerae were found to be positive for beta lactamase production. Ethanol extract of Aristolochia indica showed more significant antibacterial activity against multidrug-resistant bacteria than Toddalia asiatica. Ethanol extracts of Aristolochia indica and Toddalia asiatica showed minimum inhibitory concentration values of 50-100 MUg/ml and 100-200 MUg/ml, respectively against multidrug-resistant bacteria. From this study, it was concluded that Aristolochia indica has more potential to treat multidrug resistant bacteria than Toddalia asiatica. PMID- 26997711 TI - In vitro Cytotoxicity of Methanol Extract from Aerial Parts of Aralia cachemirica and Purified Continentalic Acid. AB - The present study was designed to evaluate the in vitro cytotoxic effect of methanol extract of aerial parts including stems, leaves and twigs of Aralia cachemirica and purified continentalic acid isolated from this extract against a panel of human cancer cell lines of varied tissues. Percentage of growth inhibition was evaluated by sulphorhodamine B assay. Purified continentalic acid showed moderate cytotoxicity against all the cell lines used. In contrast, the extract exhibited significant concentration dependant cytotoxicity against A-549 (lung), THP-1 (leukemia) and MCF-7 (breast) cell lines. This work highlights cytotoxic potential of this extract, which can further be explored for different constituents for their possible use autonomously or in combined manner in cancer therapy. The detailed analysis of their cytotoxicity has been presented in this paper. PMID- 26997712 TI - Forced Degradation Studies of Aloe Emodin and Emodin by HPTLC. AB - Anthraquinones are natural phenolic compounds, which are reported to act as anti aging, anti-inflammatory, antioxidant, anti-cancer, laxative and antitumor agents. They are abudant in plants like candle bush, aloes, cascara bark and rhubarb. The present work was to observe the effect of different forced degradation conditions by high-performance thin layer chromatography on potential markers i.e. aloe emodin and emodin. Both aloe emodin and emodin were subjected to various forced degradation studies such as oxidation, acid and alkaline hydrolysis, photolysis, hydrolytic and thermal degradation. Aloe emodin, was more susceptible to acid hydrolysis and degradation was found to a lesser extent under thermal degradation whereas significant degradation was observed under acid hydrolysis, lesser extent was observed under alkali hydrolysis for emodin. Forced degradation studies on aloe emodin and emodin gives information about its storage and intrinsic stability conditions considering the advanced pharmaceutical aspects of formulation. PMID- 26997713 TI - Consumer reporting of medicine side effects: A dream fulfilled? PMID- 26997714 TI - Metformin - For the dermatologist. AB - Metformin though primarily an antidiabetic drug, has found to play an important role in a number of cutaneous disorders. Because of its role in improving hyperinsulinemia, it has proven beneficial in hormonal acne, hidradenitis suppurativa (HS) and acanthosis nigricans. Its antiandrogenic properties further serve as an add-on to the conventional management of hirsutism associated with polycystic ovarian syndrome. Very recently, systemic usage of metformin for psoriasis and cutaneous malignancies has shown promising results. Interestingly, metformin has also been topically used in hyperpigmentary disorders with pertinent levels of improvement and happens to be the most recent addition to the list of dermatologic indications. Though an oral hypoglycemic agent to begin with, metformin today has proven to be a boon for dermatologists. PMID- 26997715 TI - The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats. AB - OBJECTIVE: Since temporal lobe epilepsy (TLE) is associated with learning and memory impairment, we investigated the beneficial effect of Vitamin E on the impaired learning and memory in the intrahippocampal kainate model of TLE in rats. MATERIALS AND METHODS: Rats were divided into sham, Vitamin E-treated sham, kainate, and Vitamin E-treated kainate. Intrahippocampal kainate was used for induction of epilepsy. Vitamin E was injected intraperitoneal (i.p.) at a dose of 200 mg/kg/day started 1 week before surgery until 1 h presurgery. Initial and step-through latencies in the passive avoidance test and alternation behavior percentage in Y-maze were finally determined in addition to measurement of some oxidative stress markers. RESULTS: Kainate injection caused a higher severity and rate of seizures and deteriorated learning and memory performance in passive avoidance paradigm and spontaneous alternation as an index of spatial recognition memory in Y-maze task. Intrahippocampal kainate also led to the elevation of malondialdehyde (MDA) and nitrite and reduced activity of superoxide dismutase (SOD). Vitamin E pretreatment significantly attenuated severity and incidence rate of seizures, significantly improved retrieval and recall in passive avoidance, did not ameliorate spatial memory deficit in Y-maze, and lowered MDA and enhanced SOD activity. CONCLUSION: Vitamin E improves passive avoidance learning and memory and part of its beneficial effect is due to its potential to mitigate hippocampal oxidative stress. PMID- 26997716 TI - The effect of learning styles and study behavior on success of preclinical students in pharmacology. AB - OBJECTIVES: To evaluate the effect of learning styles and study behaviors on preclinical medical students' pharmacology exam scores in a non-Western setting. MATERIALS AND METHODS: Grasha-Reichmann Student Learning Study Scale and a modified Study Behavior Inventory were used to assess learning styles and study behaviors of preclinical medical students (n = 87). Logistic regression models were used to evaluate the independent effect of gender, age, learning style, and study behavior on pharmacology success. RESULTS: Collaborative (40%) and competitive (27%) dominant learning styles were frequent in the cohort. The most common study behavior subcategories were study reading (40%) and general study habits (38%). Adequate listening and note-taking skills were associated with pharmacology success, whereas students with adequate writing skills had lower exam scores. These effects were independent of gender. CONCLUSIONS: Preclinical medical students' study behaviors are independent predictive factors for short term pharmacology success. PMID- 26997717 TI - Pill burden does not influence compliance with oral medication in recipients of renal transplant. AB - OBJECTIVES: Insights about the predictors of noncompliance are key to develop compliance enhancing strategy in a given therapeutic situation. Renal transplantation is a critical surgical procedure that imposes a large medication burden on patients. There is a suspicion that the large pill burden may lead to noncompliance. Our objective was to ascertain the influence of pill burden on medication compliance in renal transplant patients in the Indian sociocultural context. METHODS: A longitudinal observational study was conducted in two Tertiary Care Hospitals in Kolkata running renal transplant program - one each from the government and private sectors. Totally 120 literate adult transplant recipients were recruited through purposive sampling and followed up at 3 months intervals for 1 year. Data were collected through interview and review of prescriptions and medical records. RESULTS: Data of 110 subjects were analyzed. The pill burden was high - ranging from 10-21 (median 14) at first visit shortly after discharge to 7-22 (median 11) at last visit at 12 months in the government sector; corresponding figures in the private sector were 14-32 (median 21) and 10 28 (median 17). Pill burden increased with age. Only 60.91% of the patients were fully compliant until 1 year after transplantation. The rate of immunosuppressant noncompliance was 27.78% in government sector and 25.00% in private sector. There was no significant association between median pill burden and medication compliance. Satisfaction with caregiver support was associated with better immunosuppressant compliance. CONCLUSIONS: Noncompliance in renal transplant recipients is likely to be multifactorial. Contrary to popular belief, pill burden was not a major determinant of noncompliant behavior. PMID- 26997718 TI - Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: An in vitro study. AB - INTRODUCTION: The objective was to compare antiplatelet effect of lycopene with aspirin and to study effect of combination of the two on platelet aggregation in vitro, using platelets from healthy volunteers. MATERIALS AND METHODS: Platelets were harvested; platelet count of platelet-rich plasma adjusted to 2.5 Chi 10(5)/MUL. Aspirin (140 MUmol/L) and lycopene (4, 6, 8, 10, and 12 MUmol/L) were studied in vitro against adenosine-5'- diphosphate (ADP) (2.5 MUM/L) and collagen. RESULTS: All the concentrations of lycopene (4-12 MUmol/L) exhibited reduction in maximum platelet aggregation induced by aggregating agents ADP and collagen (P < 0.01 vs. vehicle) and were comparable with aspirin. Lycopene at concentration 10 MUmol/L showed maximum platelet inhibition (47.05% +/- 19.56%) against ADP, whereas lycopene at concentration 8 MUmol/L showed maximum platelet inhibition (54.26% +/- 30.71%) against collagen. Four MUmol/L of lycopene combined with 140 MUmol/L and 70 MUmol/L aspirin showed greater inhibition of platelets as compared to aspirin 140 MUmol/L alone, against both ADP and collagen. CONCLUSION: The study favorably compares lycopene and aspirin with respect to their antiplatelet activities against ADP and collagen. Lycopene can be considered as a potential target for modifying the thrombotic and pro inflammatory events associated with platelet activation. PMID- 26997719 TI - The effect of metamizole on ischemia/reperfusion injury in the rat ovary: An analysis of biochemistry, molecular gene expression, and histopathology. AB - OBJECTIVES: In this study, we investigated the effect of metamizole on ischemia/reperfusion (I/R) injury an analysis of biochemistry, molecular gene expression, and histopathology in the rat ovary of female albino Wistar rats. MATERIALS AND METHODS: Animals were divided into four groups; control group with induced ischemia-reperfusion (IRC), ischemia-reperfusion +100 mg/kg metamizole sodium (MS) (IRM-100), ischemia-reperfusion +200 mg/kg MS (IRM-200), and healthy group applied sham operation (SG). RESULTS: Myeloperoxidase (MPO) activity and gene expression increased significantly in IRC and IRM-100 group rat ovarian tissue compared with the SG group (P < 0.0001). However, MPO activity and gene expression in IRM-200 group ovarian tissue decreased significantly compared with the IRC and IRM-100 groups (P < 0.0001). Histopathologically, pronounced congestion, dilated vessels, hemorrhage, edema, degenerative cells, and neutrophil migration and adhesion to the endothelium were observed in the IRC and IRM-100 group ovarian tissues. A small number of congested dilated vessels, mild congestion, and edema were observed in the IRM-200 group, but no neutrophil migration and adhesion to the endothelium or degenerative cells. CONCLUSIONS: At 200 mg/kg dose metamizole prevented ovarian injury induced with I/R. This data show that metamizole can be used in the ovarian I/R injury treatment. PMID- 26997721 TI - Evaluation of cytochrome P4502E1 polymorphisms in healthy adult Western Indians and patients with antituberculous drug-induced hepatotoxicity. AB - OBJECTIVES: Cytochrome P4502E1 (CYP2E1) is involved in the metabolism of isoniazid and the mediation of its hepatotoxicity. It exhibits genetic polymorphism in humans. This study evaluated the polymorphism of CYP2E1 in adult healthy Western Indians and patients on antituberculous drugs by phenotyping and genotyping. METHODS: A 500 mg single dose of chlorzoxazone (CZX) was administered to 136 healthy adult Western Indian participants. Venous blood samples 2 h postdose were analyzed for the levels of CZX and 6-hydroxy CZX, and the metabolic ratio (MR) was calculated to determine the extent of rapid and poor metabolizers using probit plot analysis. Patients on antituberculous drugs who had raised the liver enzymes or clinical symptoms of hepatotoxicity were also recruited. Genotyping for CYP2E1 * 5B allele was performed by polymerase chain reaction - rapid fragment length polymorphism technique. RESULTS: A total of 139 healthy participants were enrolled, of which the final analysis consisted of data from 136 participants for genotyping and 137 for phenotyping. Only 1 participant had reported mild drowsiness 2 h postdose, and no other adverse events were observed. The median (range) MR of population was 0.2 (0.1-4.0), and no polymorphisms were detected using phenotype data. A total of 134/136 (98.5%) had c1/c1 genotype and 1/136 each (0.75%) had c1/c2 and c2/c2 genotypes, respectively. Of the 2/136 participants harboring c2 allele, one had MR of 0.1 (c1/c2) and another had 0.5 (c2/c2). A total of 25 cases of antituberculous drug-induced hepatotoxicity and 50 control patients were recruited, of which finally 22 cases and 49 controls were available for evaluation. All the cases had c1/c1 genotype while 42/49 (85.7%) controls had c1/c1, 6/49 (12.2%) had c1/c2, and 1/49 (2.1%) had c2/c2 genotype and the crude odds ratio was 7.9 (0.4, 145.6). CONCLUSIONS: A background prevalence of CYP2E1*B polymorphism and their activity in Western Indian population was observed. The study suggests no association between the CYP2E1 genotyping with antituberculous drug-induced hepatotoxicity. PMID- 26997722 TI - Examining the anti-candidal activity of 10 selected Indian herbs and investigating the effect of Lawsonia inermis extract on germ tube formation, protease, phospholipase, and aspartate dehydrogenase enzyme activity in Candida albicans. AB - OBJECTIVE: The objective of the study is to identify potential anti-candidal agents from natural resources and elucidate the effect of Lawsonia inermis extract on major virulent factors of Candida albicans. MATERIALS AND METHODS: Plants, the most abundant and readily available resource of diverse bioactives, were chosen for the anti-candidal screening study. Ten different plants that were proven to have antimicrobial activity but not explored much for anti-candidal activity were chosen for this study. Ethyl acetate extract of these plant leaves were tested for the anti-candidal activity. Extracts with good anti-candidal activity were further screened for its effect in C. albicans germ tube formation and enzyme (protease, phospholipase, and aspartate dehydrogenase) activity. RESULTS: Among 10 plants screened, L. inermis extract showed complete inhibition of C. albicans. On further evaluation, this extract completely inhibited C. albicans germ tube formation in serum until the end of incubation period (3 h). This extract also exhibited dose-dependent inhibitory activity against two major virulent enzymes of C. albicans, proteases (27-33%) and phospholipases (44.5%). In addition to it, this extract completely inhibited both the isoforms of constitutive candidal enzyme aspartate dehydrogenase, thereby affecting amino acid biosynthesis. CONCLUSION: Thus, this study confirms the anti-candidal potential of L. inermis and hence can be considered further for development of anti-candidal drug. PMID- 26997720 TI - Competence of medical students in communicating drug therapy: Value of role-play demonstrations. AB - OBJECTIVES: This study used role-play demonstrations to train medical students to communicate drug therapy and evaluated the perceptions on this instructional approach. MATERIALS AND METHODS: The second-year medical students who attended a prescription writing session (n = 133), participated in this study. Prescription communication was introduced by using role-play demonstrations. Participant's perceptions were explored by a self-administered questionnaire and focus group discussion. The academic achievement of attendees and nonattendees was compared with an objective structured performance evaluation (OSPE) station that tested students' competence in this skill. RESULTS: Most attendees responded to the questionnaire (81.2%). Almost all respondents expressed their desire to have similar demonstrations in other units. A large proportion of participants reported that role-play demonstrations helped them develop their communication skills, in general, confidence to communicate drug-related information in a prescription, and the ability to explain the aim of drug therapy to patients. Most trainees thought also that they developed skills to communicate instructions on drug use including drug dose, frequency of administration, duration of therapy, adverse drug reactions, and warnings. During the focus group interviews, students thought that role-play was useful but would be more beneficial if conducted frequently in small group as part of the curriculum implementation. The majority of students also reported improved competence in writing a complete prescription. Analysis of attendees and nonattendees grades in the OSPE showed that the former scored higher than the latter group (P = 0.016). CONCLUSIONS: Role-play demonstrations were well accepted by medical students and led to the development of their competence in communicating drug therapy to patients. PMID- 26997723 TI - Effect of Orexin A antagonist (SB-334867) infusion into the nucleus accumbens on consummatory behavior and alcohol preference in Wistar rats. AB - OBJECTIVE: Nucleus accumbens (NAcc) has a role in addiction and ingestive behavior. In order to assess orexinergic system involved in this, we infused Orexin A antagonist and assessed the effect on food intake fluid intake and alcohol preference in Wistar rats. MATERIALS AND METHODS: Inbred Wistar rats (n = 54) were divided into control and experimental groups (low dose and high dose). Using stereotaxic method, guide cannula was set in place bilaterally to reach NAcc. Low dose (3 ng) and high dose (6 ng) of Orexin A antagonist (SB-334867) was infused, and the food consumption, water intake and alcohol intake, and two bottle free choice preference test for alcohol were carried out in the experimental group. The control group received saline infusion and rest of the methods followed were same. The measurements were carried out immediately after the infusion, at 1 h, 2 h, 4 h, and for the whole day and represented in the figure and tables. RESULTS: A decrease in water intake observed immediately after the infusion in 1(st) h (P < 0.05) and 2(nd) h (P < 0.01), which was more in high dose group compared to low dose and controls. Alcohol intake was also following the same pattern. In two bottle free choice, rats did not show any specific preference to alcohol. CONCLUSION: There was dose dependent reduction in intake of food and fluids in treated rats. This suggested a possible role for orexinergic system in ingestive behavior. However, Orexin A may not have a role in modulation of alcohol addiction by the rewarding center NAcc. PMID- 26997724 TI - Effect of pioglitazone on the abrogated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart. AB - OBJECTIVES: The signaling pathways upstream of glycogen synthase kinase-3beta (GSK-3beta) get reduced during ischemic preconditioning (IPC) in hyperlipidemic rat heart. Pioglitazone, an insulin sensitizer, exerts cardioprotection through GSK-3beta. The objective of the study is to investigate the role of pioglitazone on the attenuated cardioprotective effect of IPC in hyperlipidemic rat heart. MATERIALS AND METHODS: The rats were administered high-fat diet for 8 weeks to induce experimental hyperlipidemia (HL). After mounting on a Langendorff apparatus, isolated perfused hearts were given four cycles of IPC; each consists of 5 min of both ischemia and reperfusion followed by 30 min of ischemia and 120 min of reperfusion. Insulin (50 mU/ml) was perfused alone and in combination with pioglitazone (2 MUM), while in other groups, this combination was repeated with wortmannin (100 nM), a selective PI3K inhibitor and rapamycin (1 nM), a selective mammalian target of rapamycin (mTOR) inhibitor, separately, and in combination. Myocardial injury was assessed by measuring infarct size and the levels of creatinine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) in the coronary effluent. RESULTS: IPC significantly decreased the infarct size and levels of LDH and CK-MB in normal but not in HL rat heart. Perfusion of insulin along with pioglitazone significantly reduced the infarct size and release of CK MB and LDH in IPC-treated HL rat hearts. Perfusion of wortmannin or rapamycin alone significantly and in combination almost completely abolished the pioglitazone-induced restored cardioprotection (P < 0.05). CONCLUSION: Cardioprotective effect of IPC gets lost in hyperlipidemic rat heart. The results suggest that perfusion of pioglitazone restored the cardioprotective effect of IPC in hyperlipidemic rat heart, an effect that may be via PI3K and mTOR. PMID- 26997725 TI - Cytotoxic potential of few Indian fruit peels through 3-(4,5-dimethylthiazol-yl) 2,5-diphenyltetrazolium bromide assay on HepG2 cells. AB - OBJECTIVE: To investigate in vitro anticancer activity of a few Indian fruit peels through 3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against HepG2 cells. MATERIALS AND METHODS: Hydroalcoholic extracts were prepared of five fruit peels, i.e., banana, lemon, guava, orange, and papaya by maceration and thereafter subjected for MTT assay to evaluate anticancer potential on HepG2 cells. Plant extract showed best activity was further fractionated with petroleum ether, chloroform, and ethyl acetate successively and screened again. Phytochemical analysis was then carried out to find out responsible components for the observed activity. RESULTS: Out of the 40 samples from five fruit peel extracts with rich folklore usage, papaya extract showed maximum activity with least inhibitory concentration50 (IC50) value of 18.5 MUg/ml. Further analysis after fractionation of the papaya peel extract, aqueous fraction showed the maximum inhibitory activity with least IC50 value of 17.3 MUg/ml. Phytochemical analysis of the aqueous fraction of papaya peel extract revealed the presence of flavonoids and glycosides. Total flavonoid content found to be 72.25 mg/g. CONCLUSION: Papaya fruit extract demonstrated the best activity against MTT assay which may be due to the presence of flavonoids. PMID- 26997726 TI - Evaluation of hepatoprotective activity of the commerson's anchovy (Stolephorus commersonnii). AB - OBJECTIVE: In the present study, we have chosen a fish Stolephorus commersonnii which is abundant in whitebait catches along Kerala coast. This fish is reported to contain higher content of essential amino acids, monounsaturated fatty acids, polyunsaturated fatty acids and minerals. The medicinal values of this species have not been reported and remain unexplored. Hence, there is a necessity to explore their uses and to conduct the pharmacological studies to ascertain their therapeutic properties. Based on literature search, no study has been carried out to scientifically validate the fish S. commersonnii possesses hepatoprotective property. Hence, this study was carried out to investigate the hepatoprotective effect of the S. commersonnii. MATERIALS AND METHODS: The fish was purchased from the fish market, Ernakulam, Kerala, India. The fish were kept on ice until processed in the lab. Fish is washed and cleaned properly. The tissue is homogenized and extracted with chloroform: methanol solvent system. The extract is transferred to a dark glass container and stored in a freezer. The preliminary analysis of fish extract was carried out by simple qualitative methods. The hepatoprotective activity of Stolephorus commersonnii (SC) extract at 300 mg/kg is carried out in isoniazid induced hepatotoxic model. The albino rats of either sex were used for these studies. RESULTS: The results of hepatoprotective study revealed that the SC extract showed a liver protective action against isoniazid induced toxicity. CONCLUSION: The present study suggests that the extract of S. commersonnii fish has therapeutic potential in the management of drug induced liver toxicity. PMID- 26997727 TI - Morphine blocks the Mesobuthus tamulus venom-induced augmentation of phenyldiguanide reflex and pulmonary edema in anesthetized rats. AB - OBJECTIVE: Pulmonary edema, a manifestation of scorpion envenomation syndrome, is attributed to cardiogenic or noncardiogenic factors. Morphine is a drug used for cardiogenic pulmonary edema and its effect on Mesobuthus tamulus (MBT) venom induced changes is not known. Therefore, we hypothesized that morphine blocks the MBT venom-induced augmentation of phenyldiguanide (PDG) reflex and pulmonary edema. MATERIALS AND METHODS: Experiments were performed on anesthetized adult female rats. Trachea and jugular vein were cannulated, and the electrocardiographic potentials were recorded by connecting needle electrodes in limb lead II configuration. PDG (10 ?g/kg, IV, bolus injection) responses were elicited by bolus injection initially, after saline/morphine (1 mg/kg) and after injecting MBT venom (100 MUg/kg). The time-response area of the PDG-induced bradycardiac response after treatment was calculated as % of the initial PDG response area. At the end of experiments, lungs were excised for determination of pulmonary water content. RESULTS: PDG produced bradycardiac response that lasted for >60 s. MBT venom augmented the PDG reflex response by 2.5 times. In morphine pretreated group, augmentation of bradycardiac response induced by MBT venom was absent. MBT venom increased the pulmonary water content, and the increase was absent in morphine pretreated animals. CONCLUSION: The results reveal that morphine prevents the MBT venom-induced augmentation of PDG reflex response and pulmonary edema. Thus, morphine can be useful in scorpion envenomation syndrome associated with pulmonary edema. PMID- 26997728 TI - Antiurolithiatic effect of lithocare against ethylene glycol-induced urolithiasis in Wistar rats. AB - AIM: This study is aimed to investigate the protective effect of Lithocare (LC) (a polyherbal formulation) against ethylene glycol (EG) induced urolithiasis in Wistar rats. MATERIALS AND METHODS: The protective effect of LC (400 and 800 mg/kg) was evaluated using EG-induced urolithiasis in rats. RESULTS: Administration of EG in drinking water resulted in hyperoxaluria, hypocalcemia as well as an increased renal excretion of phosphate. Supplementation with LC significantly reduced the urinary calcium, oxalate, and phosphate excretion dose dependently. There was a significant reduction in the levels of calcium, oxalate as well as a number of calcium oxalate crystals deposits in the kidney tissue of rats administered with LC in EG-treated rats. There was a significant reduction in creatinine, urea, uric acid, and blood urea nitrogen when LC was administered in EG-treated rats. CONCLUSIONS: From this study, it was concluded that the supplementation of LC protected EG-induced urolithiasis as it reduced the growth of urinary stones. The mechanism underlying this effect might be due to its antioxidant, diuretic, and reduction in stone-forming constituents. PMID- 26997730 TI - Pure red cell aplasia due to azathioprine therapy for Crohn's disease. AB - Various mechanisms contribute to anemia in inflammatory bowel diseases (IBD), drug-related causes being less frequent. The hematological and other adverse events of azathioprine (AZA) therapy are well documented, but drug-associated pure red cell aplasia (PRCA) is an uncommon event. We hereby describe two cases of AZA-associated PRCA in patients with Crohn's disease. The diagnosis was supported by pathological reports, and prompt hematological recovery was seen with discontinuation of the offending drug. This report highlights the need to consider this rare entity in IBD patients in appropriate settings and for adopting adequate precautionary measures. PMID- 26997729 TI - Azithromycin induced bullous fixed drug eruption. AB - Fixed drug eruption (FDE) is a common type of drug eruption seen in skin clinics. It is characterized by solitary or multiple, round to oval erythematous patches with dusky red centers, some of which may progress to bulla formation. Bullous FDE may be caused by a number of drugs. We hereby describe a case of azithromycin induced bullous FDE; to the best of our knowledge, this is the first such case being reported. PMID- 26997731 TI - Pedal edema associated with atypical antipsychotics. AB - This study describes a patient diagnosed as a case of bipolar affective disorder complaining of bothersome incidence of pedal edema 1 month after the initiation of atypical antipsychotic regimen with risperidone and quetiapine. All hematological and biochemical profiles were found to be normal. On discontinuation of risperidone, the condition remained unresolved even after 2 weeks, and the edema progressed reaching her calves. On tapering the dose of quetiapine, she started showing gradual improvement in edematous condition. Quetiapine was slowly discontinued. No further recurrence of edema occurred, and hence, no further medication changes were implemented. Pedal edema was found to be resolved within weeks of dechallenge of the regimen. Naranjo adverse drug reaction probability scale gave a score of 7 which denotes "probable" adverse drug reaction with quetiapine. PMID- 26997732 TI - Linezolid and Rasagiline - A culprit for serotonin syndrome. AB - A 65-year-old female patient was admitted to the hospital for cellulitis. She had a history of diabetes mellitus and parkinsonism on levodopa/carbidopa, rasagiline, ropinirole, trihexyphenidyl, amantadine, metformin, and glipizide. We present here a case of rare incidence of serotonin syndrome associated with linezolid and rasagiline. PMID- 26997733 TI - Serotonin syndrome presenting as pulmonary edema. AB - Serotonin syndrome (SS) is a potentially life-threatening condition resulting from excessive central and peripheral serotonergic activity. Clinically, it is a triad of mental-status changes, neuromuscular abnormalities, and autonomic disturbances. It can be caused by intentional self-poisoning, overdose, or inadvertent drug interactions. We report the case of a 58-year-old male with type 2 diabetes mellitus and obsessive compulsive disorder who developed pulmonary edema as a possible complication of SS. SS was caused by a combination of three specific serotonin re-uptake inhibitors (fluoxetine, fluvoxamine, and sertraline), linezolid, and fentanyl. The hospital course was further complicated by difficult weaning from the ventilator. SS was identified and successfully treated with cyproheptadine and lorazepam. The case highlights the importance of effective consultation-liaison and prompt recognition of SS as the presentation may be complex in the presence of co-morbid medical illness. PMID- 26997734 TI - Comparative evaluation of 2 g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections. PMID- 26997735 TI - Author Reply. PMID- 26997737 TI - Cytotoxic activity of a glaucoside from Eugenia jambolana against MCF-7 cells. PMID- 26997736 TI - Thymoquinone protects the heart against isoproterenol-induced myocardial ischemia in mice: A histopathological study. PMID- 26997738 TI - Data-driven desirability function to measure patients' disease progression in a longitudinal study. AB - Multiple outcomes are increasingly used to assess chronic disease progression. We discuss and show how desirability functions can be used to assess a patient overall response to a treatment using multiple outcome measures and each of them may contribute unequally to the final assessment. Because judgments on disease progression and the relative contribution of each outcome can be subjective, we propose a data-driven approach to minimize the biases by using desirability functions with estimated shapes and weights based on a given gold standard. Our method provides each patient with a meaningful overall progression score that facilitates comparison and clinical interpretation. We also extend the methodology in a novel way to monitor patients' disease progression when there are multiple time points and illustrate our method using a longitudinal data set from a randomized two-arm clinical trial for scleroderma patients. PMID- 26997739 TI - Electrographic Response of the Heart to Myocardial Ischemia. AB - Electrocardiographic (ECG) ST segment shifts are often used as markers for detecting myocardial ischemia. Literature suggests that the progression of ischemia, occurs from the endocardium and spreads towards the epicardium, eventually becoming transmural. Our study with animal models has found the progression of ischemia, characterized by ST elevations to be more complex and heterogeneous in its distribution. We used in situ canine preparations, wherein the animals were subjected to demand ischemia by reducing coronary flow and raising the heart rate through atrial pacing. At reduced flow, increasing the heart rate caused pockets of ST elevations to appear variously distributed in the sub-epicardial, midmyocardial and endocardial regions. Further reduction in coronary flow with simultaneous raising of the heart rate, increased the extent and magnitude of ST elevated regions, that in certain cases became transmural. PMID- 26997740 TI - Influence of stains on lesion contrast in the pits and fissures of tooth occlusal surfaces from 800-1600-nm. AB - For over one hundred years, x-rays have served as a cornerstone of dentistry. Dental radiographic imaging technologies have constantly improved, however, detecting occlusal lesions remains as one of the greatest challenges due to the low sensitivity of radiographs and the overlap of enamel. Once detected, occlusal lesions have penetrated far into the dentin, necessitating invasive restorative treatment. The adoption of near-infrared (NIR) systems in dentistry introduces the potential for early detection of occlusal lesions. Commercially available NIR systems for intra-oral applications currently operate near 800-nm; however, extrinsic stains may interfere with the detection of demineralization of the underlying enamel surface. Higher wavelengths such as 1300-nm render stains nearly transparent and enhances the contrast of sound enamel to demineralized enamel. This novel finding promotes minimally invasive dentistry and allows oral health professionals the ability to detect, image, track, and monitor early lesions without repeated exposure to ionizing radiation nor invasive treatment. PMID- 26997741 TI - Selective removal of dental composite with a diode-pumped Er:YAG laser. AB - Selective removal of dental composite with high precision is best accomplished using lasers operating at high pulse repetition rates focused to a small spot size. Conventional flash-lamp pumped Er:YAG lasers are poorly suited for this purpose, but new diode-pumped Er:YAG lasers have become available operating at high pulse repetition rates. The purpose of this study was to compare the ablation rates and selectivity of enamel and composite for a 30 W diode-pumped Er:YAG laser operating with a pulse duration of 30-50-MUs and evaluate it's suitability for the selective removal of composite from tooth surfaces. The depth of ablation and changes in surface morphology were assessed using digital microscopy. The fluence range of 30-50 J/cm2 appeared optimal for the removal of composite, and damage to sound enamel was limited to less than 100-MUm after the removal of composite as thick as 700-800-MUm. Future studies will focus on the use of methods of feedback to further increase selectivity. PMID- 26997742 TI - Selective removal of esthetic composite restorations with spectral guided laser ablation. AB - Dental composites are used for a wide range of applications such as fillings for cavities, adhesives for orthodontic brackets, and closure of gaps (diastemas) between teeth by esthetic bonding. Anterior restorations are used to replace missing, diseased and unsightly tooth structure for both appearance and function. When these restorations must be replaced, they are difficult to remove mechanically without causing excessive removal or damage to enamel because dental composites are color matched to teeth. Previous studies have shown that CO2 lasers have high ablation selectivity and are well suited for removal of composite on occlusal surfaces while minimizing healthy tissue loss. A spectral feedback guidance system may be used to discriminate between dental composite and dental hard tissue for selective ablation of composite material. The removal of composite restorations filling diastemas is more challenging due to the esthetic concern for anterior teeth. The objective of this study is to determine if composite spanning a diastema between anterior teeth can be removed by spectral guided laser ablation at clinically relevant rates with minimal damage to peripheral healthy tissue and with higher selectivity than a high speed dental hand-piece. PMID- 26997743 TI - Assessment of simulated lesions on primary teeth with near-infrared imaging. AB - Previous studies have demonstrated that the structural changes on enamel due to demineralization and remineralization can be exploited through optical imaging methods such as QLF, thermal and NIR imaging. The purpose of this study is to investigate whether PS-OCT and NIR reflectance imaging can be utilized to assess lesion structure in artificial enamel lesions on the smooth surfaces of primary teeth exposed to fluoride. The smooth coronal surfaces of primary teeth (n=25) were divided into 4 windows: sound, demineralization, demineralization with remineralization and APF with demineralization. Windows were treated with either acidulated phosphate fluoride (APF) for 1 minute, a demineralization solution for 4 days, and/or an acidic remineralization solution for 12 days. The samples were imaged using PS-OCT, QLF and NIR reflectance at 1400-1700 nm wavelengths. This study demonstrated that both PS-OCT and NIR reflectance imaging were suitable for assessing lesion structure in the smooth surfaces of primary dentition. PMID- 26997744 TI - Contribution of BRCA1 and BRCA2 Germline Mutations to Early Algerian Breast Cancer. AB - Breast cancer is the most common female malignancy and the leading cancer mortality cause among Algerian women. Germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast cancer have not been clearly identified within the Algerian population. It is necessary to study the BRCA1/2 genes involvement in the Algerian breast cancer occurrence. We performed this study to define germline mutations in BRCA1/2 and their implication in breast cancer among young women from eastern Algeria diagnosed or treated with primary invasive breast cancer at the age of 40 or less who were referred to Anti-Cancer Center of Setif, Algeria. Case series were unselected for family history. Eight distinct pathogenic mutations were identified in eight unrelated families. Three deleterious mutations and one large genomic rearrangement involving deletion of exon 2 were found in BRCA1 gene. In addition, four mutations within the BRCA2 gene and one large genomic rearrangement were identified. Novel mutation was found among Algerian population. Moreover, five variants of uncertain clinical significance and favor polymorphisms were identified. Our data suggest that BRCA1/2 mutations are responsible for a significant proportion of breast cancer in Algerian young women. PMID- 26997745 TI - Is Sex Like Driving? HIV Prevention and Risk Compensation. AB - Risk compensation has been called the "Achilles' heel" of HIV prevention policies (Cassell et al 2006). This paper examines the behavioral response to male circumcision, a major HIV prevention policy currently being implemented throughout much of Sub-Saharan Africa. Contrary to the presumption of risk compensation, we find that the response due to the perceived reduction in HIV transmission appears to have been a reduction in risky sexual behavior. We suggest a mechanism for this finding: circumcision may reduce fatalism about acquiring HIV/AIDS and increase the salience of the tradeoff between engaging in additional risky behavior and avoiding acquiring HIV. We also find what appears to be a competing effect that does not operate through the circumcision recipient's belief about the reduction in the risk of acquiring HIV. PMID- 26997746 TI - A Smooth Bootstrap Procedure towards Deriving Confidence Intervals for the Relative Risk. AB - Given a pair of sample estimators of two independent proportions, bootstrap methods are a common strategy towards deriving the associated confidence interval for the relative risk. We develop a new smooth bootstrap procedure, which generates pseudo-samples from a continuous quantile function. Under a variety of settings, our simulation studies show that our method possesses a better or equal performance in comparison with asymptotic theory based and existing bootstrap methods, particularly for heavily unbalanced data in terms of coverage probability and power. We illustrate our procedure as applied to several published data sets. PMID- 26997748 TI - Factors shaping the HIV-competence of two primary schools in rural Zimbabwe. AB - We present multi-method case studies of two Zimbabwean primary schools - one rural and one small-town. The rural school scored higher than the small-town school on measures of child well-being and school attendance by HIV-affected children. The small-town school had superior facilities, more teachers with higher morale, more specialist HIV/AIDS activities, and an explicit religious ethos. The relatively impoverished rural school was located in a more cohesive community with a more critically conscious, dynamic and networking headmaster. The current emphasis on HIV/AIDS-related teacher training and specialist school based activities should be supplemented with greater attention to impacts of school leadership and the nature of the school-community interface on the HIV competence of schools. PMID- 26997749 TI - Optimal Sampling-Based Motion Planning under Differential Constraints: the Drift Case with Linear Affine Dynamics. AB - In this paper we provide a thorough, rigorous theoretical framework to assess optimality guarantees of sampling-based algorithms for drift control systems: systems that, loosely speaking, can not stop instantaneously due to momentum. We exploit this framework to design and analyze a sampling-based algorithm (the Differential Fast Marching Tree algorithm) that is asymptotically optimal, that is, it is guaranteed to converge, as the number of samples increases, to an optimal solution. In addition, our approach allows us to provide concrete bounds on the rate of this convergence. The focus of this paper is on mixed time/control energy cost functions and on linear affine dynamical systems, which encompass a range of models of interest to applications (e.g., double-integrators) and represent a necessary step to design, via successive linearization, sampling based and provably-correct algorithms for non-linear drift control systems. Our analysis relies on an original perturbation analysis for two-point boundary value problems, which could be of independent interest. PMID- 26997750 TI - Empirical Dynamic Model Identification for Blood-Glucose Dynamics in Response to Physical Activity. AB - In this paper, the dynamic response of blood glucose concentration in response to physical activity of people with Type 1 Diabetes Mellitus (T1DM) is captured by subspace identification methods. Activity (input) and subcutaneous blood glucose measurements (output) are employed to construct a personalized prediction model through semi-definite programming. The model is calibrated and subsequently validated with non-overlapping data sets from 15 T1DM subjects. This preliminary clinical evaluation reveals the underlying linear dynamics between blood glucose concentration and physical activity. These types of models can enhance our capabilities of achieving tighter blood glucose control and early detection of hypoglycemia for people with T1DM. PMID- 26997751 TI - Mechanism of Hg(II) Immobilization in Sediments by Sulfate-Cement Amendment. AB - Reactive amendments such as Portland and super-sulfate cements offer a promising technology for immobilizing metalloid contaminants such as mercury (Hg) in soils and sediments through sequestration in less bioavailable solid forms. Tidal marsh sediments were reacted with dissolved Hg(II) in synthetic seawater and fresh water solutions, treated with Portland cement and FeSO4 amendment, and aged for up to 90 days. Reacted solids were analyzed with bulk sequential extraction methods and characterized by powder X-ray diffraction (XRD), electron microscopy, and synchrotron X-ray absorption spectroscopy at the Hg LIII- and S K-edge. In amended sediments, XRD, SEM and sulfur K-edge XANES indicated formation of gypsum in seawater experiments or ettringite-type (Ca6Al2(SO4)3(OH)12.26H2O) phases in fresh water experiments, depending on the final solution pH (seawater ~8.5; freshwater ~10.5). Analysis of Hg EXAFS spectra showed Cl and Hg ligands in the first- and second-coordination shells at distances characteristic of a polynuclear chloromercury(II) salt, perhaps as a nanoparticulate phase, in both seawater and fresh water experiments. In addition to the chloromercury species, a smaller fraction (~20-25%) of Hg was bonded to O atoms in fresh water sample spectra, suggesting the presence of a minor sorbed Hg fraction. In the absence of amendment treatment, Hg sorption and resistance to extraction can be accounted for by relatively strong binding by reduced S species present in the marsh sediment detected by S XANES. Thermodynamic calculations predict stable aqueous Hg-Cl species at seawater final pH, but higher final pH in fresh water favors aqueous Hg-hydroxide species. The difference in Hg coordination between aqueous and solid phases suggests that the initial Hg-Cl coordination was stabilized in the cement hydration products and did not re-equilibrate with the bulk solution with aging. Collectively, results suggest physical encapsulation of Hg as a polynuclear chloromercury(II) salt as the primary immobilization mechanism. PMID- 26997752 TI - Materials that harness and modulate the immune system. AB - Recently, biomaterial scientists have married materials engineering and immunobiology to conceptualize new immunomodulatory materials. This special class of biomaterials can modulate and harness the innate properties of immune functionality for enhanced therapeutic efficacy. Generally, two fundamental strategies are followed in the design of immunomodulatory biomaterials: (1) immuno-evasive (immuno-mimetic, immuno-suppressing, or immuno-inert) biomaterials and (2) immuno-activating or immuno-enhancing biomaterials. This article highlights the development and application of a number of immunomodulatory materials, categorized by these two general approaches. PMID- 26997753 TI - Personality trait change across late childhood to young adulthood: Evidence for nonlinearity and sex differences in change. AB - We explored patterns of self-reported personality trait change across late childhood through young adulthood in a sample assessed up to 4 times on the lower order facets of Positive Emotionality (PEM), Negative Emotionality (NEM), and Constraint (CON). Multilevel modeling analyses were used to describe both group- and individual-level change trajectories across this time span. There was evidence for nonlinear age-related change in most traits, and substantial individual differences in change for all traits. Gender differences were detected in the change trajectories for several facets of NEM and CON. Findings add to the literature on personality development by demonstrating robust nonlinear change in several traits across late childhood to young adulthood, as well as deviations from normative patterns of maturation at the earliest ages. PMID- 26997754 TI - Drinking and Dating: Examining the Link between Relationship Satisfaction, Hazardous Drinking, and Readiness-to-Change in College Dating Relationships. AB - The present study examined the influence of relationship satisfaction on readiness-to-change alcohol use and the influence of hazardous drinking on readiness-to-change relationship issues in college student dating relationships. A sample of 219 college students in a current dating relationship (aged 18-25) completed self-report measures of dating relationship satisfaction, alcohol use, readiness-to-change alcohol use, and readiness-to-change relationship issues via an online survey from August to December 2011. Participants were grouped on the basis of their scores on measures of alcohol use (hazardous drinkers vs. nonhazardous drinkers) and relationship satisfaction (high vs. low). Results indicated that alcohol use was negatively correlated with relationship satisfaction. Furthermore, hazardous drinkers with high relationship satisfaction indicated more readiness-to-change alcohol use than hazardous drinkers with low relationship satisfaction. Alcohol problems were not related to readiness-to change relationship issues. These findings indicate that highly satisfied dating relationships during college may positively influence readiness-to-change heavy drinking habits among college students. PMID- 26997756 TI - Determinants of Noncompliance to Clinic Appointments and Medications among Nigerian Children with Epilepsy: Experience in a Tertiary Health Facility in Enugu, Nigeria. AB - Purpose. To determine the frequency and determinants of noncompliance to clinic appointment and medication among Nigerian children with epilepsy. Method. This is a cross-sectional survey of noncompliance to clinic appointments and medication among 113 consecutive children with epilepsy attending the Paediatric Neurology Clinic of University of Nigeria Teaching Hospital, Enugu, southeastern Nigeria. Results. Noncompliance to clinic appointment and medication was 23% and 15.3%, respectively. The major reasons given were lack of finance, clashing with school time, and forgetting to take the drugs. Children whose mothers were less educated and unemployed were more likely to miss clinic appointments. Noncompliance to medication was associated with poor seizure control. Children that were on phenobarbitone were more likely to be noncompliant with medication than those on sodium valproate and/or carbamazepine. Conclusion. Missed clinic appointment and medication noncompliance are common among Nigerian children with epilepsy and financial constraint is the most common reason. PMID- 26997755 TI - Cognitive Attributes, Attention, and Self-Efficacy of Adequate and Inadequate Responders in a Fourth Grade Reading Intervention. AB - We examined cognitive attributes, attention, and self-efficacy of fourth grade struggling readers who were identified as adequate responders (n = 27), inadequate responders with comprehension only deficits (n = 46), and inadequate responders with comprehension and word reading deficits (n = 52) after receiving a multicomponent reading intervention. We also included typical readers (n = 40). These four groups were compared on measures of nonverbal reasoning, working memory, verbal knowledge, listening comprehension, phonological awareness, and rapid naming as well as on teacher ratings of attention problems and self reported self-efficacy. The two inadequate responder groups demonstrated difficulties primarily with verbal knowledge and listening comprehension compared to typical readers and adequate responders. Phonological awareness and rapid naming differentiated the two inadequate responder groups. In addition, both inadequate responder groups showed more attention problems and low self-efficacy compared to typical readers. PMID- 26997757 TI - Early Parental Positive Behavior Support and Childhood Adjustment: Addressing Enduring Questions with New Methods. AB - A large literature provides strong empirical support for the influence of parenting on child outcomes. The current study addresses enduring research questions testing the importance of early parenting behavior to children's adjustment. Specifically, we developed and tested a novel multi-method observational measure of parental positive behavior support at age 2. Next, we tested whether early parental positive behavior support was related to child adjustment at school age, within a multi-agent and multi-method measurement approach and design. Observational and parent-reported data from mother-child dyads (N = 731; 49 percent female) were collected from a high-risk sample at age 2. Follow-up data were collected via teacher report and child assessment at age 7.5. The results supported combining three different observational methods to assess positive behavior support at age 2 within a latent factor. Further, parents' observed positive behavior support at age 2 predicted multiple types of teacher-reported and child-assessed problem behavior and competencies at 7.5 years old. Results supported the validity and predictive capability of a multi method observational measure of parenting and the importance of a continued focus on the early years within preventive interventions. PMID- 26997758 TI - CD97/ADGRE5 Inhibits LPS Induced NF-kappaB Activation through PPAR-gamma Upregulation in Macrophages. AB - CD97/ADGRE5 protein is predominantly expressed on leukocytes and belongs to the EGF-TM7 receptors family. It mediates granulocytes accumulation in the inflammatory tissues and is involved in firm adhesion of PMNC on activated endothelial cells. There have not been any studies exploring the role of CD97 in LPS induced NF-kappaB activation in macrophages. Therefore, we first measured the CD97 expression in LPS treated human primary macrophages and subsequently analyzed the levels of inflammatory factor TNF-alpha and transcription factor NF kappaB in these macrophages that have been manipulated with either CD97 knockdown or overexpression. We found that a reported anti-inflammatory transcription factor, PPAR-gamma, was involved in the CD97 mediated NF-kappaB suppression. Furthermore, by immunofluorescence staining, we established that CD97 overexpression not only inhibited LPS induced p65 expression in the nucleus but also promoted the PPAR-gamma expression. Moreover, using CD97 knockout THP-1 cells, we further demonstrated that CD97 promoted PPAR-gamma expression and decreased LPS induced NF-kappaB activation. In conclusion, CD97 plays a negative role in LPS induced NF-kappaB activation and TNF-alpha secretion, partly through PPAR-gamma upregulation. PMID- 26997759 TI - miR-146a Attenuates Inflammatory Pathways Mediated by TLR4/NF-kappaB and TNFalpha to Protect Primary Human Retinal Microvascular Endothelial Cells Grown in High Glucose. AB - Pathological mechanisms underlying diabetic retinopathy are still not completely understood. Increased understanding of potential cellular pathways responsive to hyperglycemia is essential to develop novel therapeutic strategies for diabetic retinopathy. A growing body of evidence shows that microRNA (miRNA) play important roles in pathological mechanisms involved in diabetic retinopathy, as well as possessing potential as novel therapeutic targets. The hypothesis of this study was that miR-146a plays a key role in attenuating hyperglycemia-induced inflammatory pathways through reduced TLR4/NF-kappaB and TNFalpha signaling in primary human retinal microvascular endothelial cells (REC). We cultured human REC in normal (5 mM) glucose or transferred to high glucose medium (25 mM) for 3 days. Transfection was performed on REC with miRNA mimic (hsa-miR-146a-5p). Our results demonstrate that miR-146a expression was decreased in human REC cultured in high glucose. Overexpression of miR-146a using mimics reduced the levels of TLR4/NF-kappaB and TNFalpha in REC cultured in high glucose. Both MyD88-dependent and -independent signaling were decreased by miR-146a overexpression in REC in high glucose conditions. The results suggest that miR-146a is a potential therapeutic target for reducing inflammation in REC through inhibition of TLR4/NF kappaB and TNFalpha. Our study will contribute to understanding of diabetic retinal pathology, as well as providing important clues to develop therapeutics for clinical applications. PMID- 26997760 TI - Role of Transforming Growth Factor-beta1 and Smads Signaling Pathway in Intrauterine Adhesion. AB - The aim of the study was to evaluate the role of Smad3, Smad7, and TGF-beta1 in intrauterine adhesion (IUA) patients and experimental rabbit models. 60 IUA patients, 30 control participants, and 18 female rabbits were enrolled in this study. We found that the plasma concentrations and protein expressions of TGF beta1 were significantly increased in patients and experimental rabbits compared to those in controls (P < 0.05). Furthermore, the mRNA and protein expression levels of Smad3 were significantly elevated, while Smad7 level was markedly decreased in the patients and experimental rabbits compared with controls (P < 0.05). This altered ratio recommended that IUA was positively correlated to the mRNA and protein expression levels of Smad3, Smad7, and TGF-beta1 in blood and uterine tissue. Moreover, we used the specific inhibitor of Smad3 (SIS3) in experimental rabbit. SIS3 obviously reduced the mRNA and protein expression of smad3 and TGF-beta1, while it increased Smad7 expression in the treatment groups as compared with IUA rabbits (P < 0.05). Our study suggested that TGF beta1/Smad3/smad7 is a major pathway which plays an important role in the regulation of the IUA and specific inhibitor of Smad3 (SIS3) may provide a new therapeutic strategy for IUA. PMID- 26997762 TI - Flashbulb Memories. AB - We review and analyze the key theories, debates, findings, and omissions of the existing literature on flashbulb memories (FBMs), including what factors affect their formation, retention, and degree of confidence. We argue that FBMs do not require special memory mechanisms and are best characterized as involving both forgetting and mnemonic distortions, despite a high level of confidence. Factual memories for FBM-inducing events generally follow a similar pattern. Although no necessary and sufficient factors straightforwardly account for FBM retention, media attention particularly shapes memory for the events themselves. FBMs are best characterized in term of repetitions, even of mnemonic distortions, whereas event memories evidence corrections. The bearing of this literature on social identity and traumatic memories is also discussed. PMID- 26997763 TI - Initial Treatment: Prostaglandin Analog or Selective Laser Trabeculoplasty. AB - Prostaglandin analogs (PGA) have been the initial treatment of choice in many patients with glaucoma. However, there is an increasing awareness that non adherence and disruption of the ocular surface may limit PGA utility and tolerability respectively in some patients. In an eye with an open iridocorneal angle, these issues can potentially be addressed with the use of laser trabeculoplasty (LT). This therapy can achieve long-term intraocular pressure reduction following 1 to 2 treatment sessions without the ongoing need to apply medication (and preservatives) to the ocular surface. Whether PGAs or LT should be used in a given individual will also be influenced by other important factors including efficacy, response rate, tolerability, complications, cost and accessibility. This review examines these issues in relation to the initiation of primary therapy. How to cite this article: Clement CI. Initial Treatment: Prostaglandin Analog of Selective Laser Trabeculoplasty. J Current Glau Prac 2012;6(3):99-103. PMID- 26997764 TI - Controversy: Is Benzalkonium Chloride Necessary in Antiglaucoma Drops? AB - Medical therapy is the first-line option in glaucoma management, with benzalkonium chloride (BAC) being the most frequently used preservative in antiglaucoma medications. Its use is however, known to be associated with deleterious effects on the ocular surface. This review is an attempt to critically evaluate whether BAC really is indispensable for better bioavailability of antiglaucoma drugs and consequently, better IOP control. How to cite this article: Louati Y, Shaarawy T. Controversy: Is Benzalkonium Chloride Necessary in Antiglaucoma Drops? J Current Glau Prac 2012;6(3):104-107. PMID- 26997761 TI - Parallel Aspects of the Microenvironment in Cancer and Autoimmune Disease. AB - Cancer and autoimmune diseases are fundamentally different pathological conditions. In cancer, the immune response is suppressed and unable to eradicate the transformed self-cells, while in autoimmune diseases it is hyperactivated against a self-antigen, leading to tissue injury. Yet, mechanistically, similarities in the triggering of the immune responses can be observed. In this review, we highlight some parallel aspects of the microenvironment in cancer and autoimmune diseases, especially hypoxia, and the role of macrophages, neutrophils, and their interaction. Macrophages, owing to their plastic mode of activation, can generate a pro- or antitumoral microenvironment. Similarly, in autoimmune diseases, macrophages tip the Th1/Th2 balance via various effector cytokines. The contribution of neutrophils, an additional plastic innate immune cell population, to the microenvironment and disease progression is recently gaining more prominence in both cancer and autoimmune diseases, as they can secrete cytokines, chemokines, and reactive oxygen species (ROS), as well as acquire an enhanced ability to produce neutrophil extracellular traps (NETs) that are now considered important initiators of autoimmune diseases. Understanding the contribution of macrophages and neutrophils to the cancerous or autoimmune microenvironment, as well as the role their interaction and cooperation play, may help identify new targets and improve therapeutic strategies. PMID- 26997765 TI - Knowledge, Attitudes and Self-care Practices associated with Glaucoma among Hospital Personnel in a Tertiary Care Center in North India. AB - PURPOSE: To determine the level of correct knowledge about glaucoma and attitudes toward blindness prevention and treatment and how these factors influence self care practices among hospital personnel. METHODS: In this tertiary hospital based, cross-sectional study, a random sample of 119 staff members including 23 physicians (nonophthalmologists) and 96 nursing staff were administered a self designed knowledge, attitudes, practice (KAP) questionnaire about glaucoma. RESULTS: All 119 personnel [34 (28.57%) males; 85 (71.42%) females] were aware of glaucoma. Most physicians (80.76%) and nurses (65.26%) understood that glaucoma was associated with a high intraocular pressure and had an effect on the optic nerve. Twenty-four percent of physicians and nurses did not know that it is important for family members of glaucoma patients to be more concerned about getting the disease. As regards 'treatment priority' between cataract, glaucoma and diabetic retinopathy; 76.91% physicians and 60% nurses placed glaucoma first. Out of total blindness, stroke or paralysis, cancer, schizophrenia and heart disease, blindness prevention was first priority for 9 (34.60%) physicians and 15 (15.78%) nurses. A recent visit to an eye practitioner (p = 0.012) was a significant predictor of knowledge of glaucoma as a blinding disease. CONCLUSION: Educating hospital workers on the symptoms of glaucoma and visual impairment can be an important step toward preventive ophthalmic care. How to cite this article: Ichhpujani P, Bhartiya S, Kataria M, Topiwala P. Knowledge, Attitudes and Self care Practices associated with Glaucoma among Hospital Personnel in a Tertiary Care Center in North India. J Current Glau Prac 2012;6(3):108-112. PMID- 26997766 TI - Imaging of the Lamina Cribrosa using Swept-Source Optical Coherence Tomography. AB - The lamina cribrosa (LC) is the presumed site of axonal injury in glaucoma. Its deformation has been suggested to contribute to optic neuropathy by impeding axoplasmic flow within the optic nerve fibers, leading to apoptosis of retinal ganglion cells. To visualize the LC in vivo, optical coherence tomography (OCT) has been applied. Spectral domain (SD)-OCT, used in conjunction with recently introduced enhanced depth imaging (EDI)-OCT, has improved visualization of deeper ocular layers, but in many individuals it is still limited by inadequate resolution, poor image contrast and insufficient depth penetrance. The posterior laminar surface especially is not viewed clearly using these methods. New generation high-penetration (HP)-OCTs, also known as swept-source (SS)-OCT, are capable to evaluate the choroid in vivo to a remarkable level of detail. SS-OCTs use a longer wavelength (1,050 nm instead of 840 nm) compared to the conventional techniques. We review current knowledge of the LC, findings from trials that use SD-OCT and EDI-OCT, and our experience with a prototype SS-OCT to visualize the LC in its entirety. Key Points What is known? * The LC is the presumed site of axonal injury in glaucoma * Compared to spectral domain-OCT, enhanced depth imaging-OCT improves imaging of the LC * Even so, currently used SD-OCT techniques are restricted by poor wavelength penetrance of the deeper ocular layers What our findings add? * SS-OCT may be a superior imaging modality for deep ocular structures * Prior studies used SS-OCT to evaluate choroidal thickness in both healthy and 'normal tension glaucoma' eyes * SS-OCT enables good evaluation of three-dimension (3D) lamina cribrosa morphology. How to cite this article: Nuyen B, Mansouri K, Weinreb RN. Imaging of the Lamina Cribrosa using Swept-Source Optical Coherence Tomography. J Current Glau Prac 2012;6(3): 113-119. PMID- 26997767 TI - The Need to maintain Intraocular Pressure over 24 Hours. AB - Glaucoma patients who appear to be stable based on daytime in-clinic intraocular pressure (IOP) measurements may not be fully controlled over each 24-hour period. Given that there is sufficient evidence that IOP fluctuation may impact progression, the aim of management of glaucoma thus, is to achieve a target IOP with minimal diurnal fluctuation. How to cite this article: Bhartiya S, Ichhpujani P. The Need to Maintain Intraocular Pressure over 24 Hours. J Current Glau Prac 2012;6(3):120-123. PMID- 26997768 TI - Tonometry and Care of Tonometers. AB - Intraocular pressure (IOP) remains the only modifiable risk factor in the management of glaucoma. Hence, IOP and its appropriate measurement deserve our ongoing interest. Over the years, not only has our understanding of glaucoma changed but also has changed our approach to the measurement of the IOP. This review is an attempt to elucidate the commonly techniques of tonometry, and critically evaluate each of them, in current glaucoma practice. How to cite this article: Maheshwari R, Choudhari NS, Singh MD. Tonometry and Care of Tonometers. J Current Glau Prac 2012;6(3):124-130. PMID- 26997769 TI - Revision Trabeculectomy: Pearls and Pitfalls. AB - Revision trabeculectomy is used to describe any surgical intervention subsequent to an existing trabeculectomy. Mostly, it is used to describe resurgery for failure of trabeculectomy, as defined by inadequate pressure control. Revision may also be performed for unsafe, uncomfortable or leaking blebs. Mostly bleb failure occurs within the subconjunctival space, although the flap and ostium may be involved or causative. Clear surgical principles, meticulous surgical technique and scrupulous postoperative care are key to successful revision surgery. This review is an attempt to elucidate the technique of bleb revision for bleb failure. How to cite this article: Coote M, Crowston J. Revision Trabeculectomy: Pearls and Pitfalls. J Current Glau Prac 2012;6(3):131-138. PMID- 26997771 TI - Editorial. PMID- 26997770 TI - Tube Exposure Repair. AB - All across the world, glaucomatologists are adopting broader use of glaucoma drainage implants even as a primary surgical modality. To avoid tube exposure, which may predispose the eye to endophthalmitis, the implanted tube must be covered by a patch graft. However, these patch grafts also carry a high rate of progressive thinning and erosion, which is believed to result from the lack of cellular infiltration from the surrounding host conjunctival stroma and poor integration of these patch grafts to the host tissue. An ideal patch graft should offer good tensile strength, be suitable for tectonic support, and have biological activities to promote cellular infiltration by the surrounding host conjunctival stroma, thus reducing progressive allogeneic patch graft thinning/erosion. This review talks about various materials and modalities used for an exposed tube repair. How to cite this article: Oana S, Vila J. Tube Exposure Repair. J Current Glau Prac 2012;6(3):139-142. PMID- 26997772 TI - Preimplantation Flow Testing of Ahmed Glaucoma Valve and the Early Postoperative Clinical Outcome. AB - PURPOSE: The Ahmed glaucoma valve (AGV) implant is designed to prevent early postoperative hypotony. There is evidence of variation in hypotony rates in clinical trials which may be due to surgical technique variation, entry site leakage or valve defects from 'over priming'. We describe a simple preimplantation gravity driven test to assess valve function after priming that may reduce hypotony rates. MATERIALS AND METHODS: Retrospective case note review. An in vivo flow test of AGVs, based on the gravity driven test was introduced prior to implantation. The onset and offset of flow through the valve was measured by altering the height of a bottle of balanced saline solution. We rejected the AGV, if there was fluid still flowing at 10 cm (7 mm Hg) or if there was no flow at 17 cm of water (12 mm Hg). The AGV implantation surgery was without mitomycin C, with a 25G needle entry tract, a corneal or scleral patch graft tube cover and without intracameral viscoelastic. RESULTS: Twenty Ahmed valves were implanted in 16 patients between July 2008 and October 2009. Test failure resulted in four AGV being rejected. The mean preoperative pressure was 29 mm Hg (range, 10-57 mm Hg) and the intraocular pressure (IOP) at 7 days postoperatively was 15 mm Hg (range, 3-52 mm Hg). Hypotony, defined as an IOP of less than 5 mm Hg on two consecutive assessments, was present in two eyes (10%). CONCLUSION: In vivo flow testing is an important safety check for the AGV. There are also other mechanisms after implantation that can cause an unexpected high or low IOP. How to cite this article: Jones E, Alaghband P, Cheng J, Beltran-Agullo L, Lim KS. Preimplantation Flow Testing of Ahmed Glaucoma Valve and the Early Postoperative Clinical Outcome. J Current Glau Prac 2013;7(1):1-5. PMID- 26997773 TI - Presenting Visual Acuity and Ocular Comorbidity in Patients with Primary Open Angle Glaucoma in a Private Tertiary Eye Center in Nigeria. AB - PURPOSE: To determine the presenting visual acuity (VA) of patients with primary open angle glaucoma (POAG) and the relationship to ocular comorbidity. MATERIALS AND METHODS: A retrospective case note audit was undertaken in Eye Foundation Hospital, Calabar, between 1st January 2010 and 31st June 2011. The case notes of all newly presenting patients diagnosed with POAG were retrieved and data were extracted for analysis. Inclusion criteria for glaucoma was defined. RESULTS: Out of a total of 320 new patients, 88 patients were diagnosed with POAG, with a prevalence of 27.5% (95% CI: 22.7-32.7). The mean age for males is 57.1 +/- 8.8 while that of females is 52.6 +/- 11.2 and the total mean of 55.8 +/- 9.7. Of the 88 patients, there were 84 self referrals [95.5% (95% CI: 88.8-98.7)], of these, 45, 53.6% (95% CI: 42.4-64.5) were for second opinion. There was no statistical significance between the gender, education and occupation and the level of VA seen on presentation. The best corrected visual acuity (BCVA ) in the right and left eye respectively, was significantly (p < 0.0001) related to the cup disk ratio. Ocular comorbid conditions were seen in 19 (22%) patients in the study. The presenting BCVA was significantly related to the presence of ocular comorbidity in the best eye. Comorbidity was not strongly related to the age of the patients. CONCLUSION: The course of glaucomatous progression is highly variable, identifying factors that not only predict progression but influence the VA and ocular health of the eye can help to guide clinical practice and patient treatment and monitoring. How to cite this article: Duke R, Akinye A, Ameh S. Presenting Visual Acuity and Ocular Comorbidity in Patients with Primary Open Angle Glaucoma in a Private Tertiary Eye Center in Nigeria. J Current Glau Prac 2013;7(1):6-10. PMID- 26997774 TI - A Comfort Survey of Timolol Hemihydrate 0.5% Solution Once or Twice Daily vs Timolol Maleate in Sorbate. AB - OBJECTIVE: To evaluate by survey the comfort upon instillation of timolol hemihydrate compared to timolol maleate with potassium sorbate. DESIGN: A prospective, multicenter, observational, non-interventional study. PARTICIPANTS: One hundred and three patients of open-angle glaucoma or ocular hypertension who were >=21 years old and were currently prescribed timolol hemihydrate (once or twice daily) or timolol maleate with potassium sorbate once daily as monotherapy or as a part of two-drug therapy. MATERIALS AND METHODS: Study was performed at seven clinical sites in the United States. Patients were surveyed on comfort upon instillation of timolol hemihydrate compared to timolol maleate with potassium sorbate. RESULTS: A difference between timolol hemihydrate and timolol maleate with potassium sorbate for questions 1 (burning/stinging on instillation, p < 0.001) and 4 (tearing on instillation, p = 0.024) was noted. There were no differences between treatment groups for any other question (p > 0.05). CONCLUSION: This survey suggests that timolol hemihydrate is associated with less stinging/burning and tearing than timolol maleate with potassium sorbate. How to cite this article: Stewart WC, Oehler JC, Choplin NT, Markoff JI, Moster MR, Ichhpujani P, Nelson LA. A Comfort Survey of Timolol Hemihydrate 0.5% Solution Once or Twice Daily vs Timolol Maleate in Sorbate. J Current Glau Prac 2013;7(1):11-16. PMID- 26997775 TI - IOP Maintenance in SLT-treated Eyes following Subsequent Phacoemulsification and IOL. AB - To assess whether the intraocular pressure (IOP) in selective laser trabeculoplasty (SLT)-treated eyes is maintained following subsequent phacoemulsification and lens implant (phaco + IOL). Retrospective single center review of 45 eyes of 35 patients who had open angle glaucoma (OAG), successfully treated by SLT by the same surgeon (EA), and then had routine phaco + IOL by same surgeon (EA). The main outcome measures were baseline (SLT-treated) IOP and IOP at 3, 6 and 12 months following subsequent routine phaco + Intraocular lens (IOL). Secondary outcome measures were visual acuity pre- and post (phaco + IOL) and any complications. The study found that IOP reduction with SLT is not significantly affected by subsequent phaco + IOL in patients with OAG. How to cite this article: Ansari E. IOP Maintenance in SLT-treated Eyes following Subsequent Phacoemulsification and IOL. J Current Glau Prac 2013;7(1):17-18. PMID- 26997776 TI - Intraocular Pressure rise after Anti-VEGF Treatment: Prevalence, Possible Mechanisms and Correlations. AB - Intraocular pressure (IOP) rise after anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD) can be either short-term or long-term and may require medical intervention. Short-term IOP spikes are a fairly common and well recognized complication of anti-VEGF injections. Long-term IOP rise is less well-understood and disputed as a complication by some authors. We try to review current literature on the subject and especially studies focused on the prevalence of this complication, speculate on possible mechanisms of IOP rise and discuss correlations of long-term IOP rise with the nature of the injected agent, average number of injections, previous glaucoma history and other factors. How to cite this article: Kampougeris G, Spyropoulos D, Mitropoulou A. Intraocular Pressure rise after Anti-VEGF Treatment: Prevalence, Possible Mechanisms and Correlations. J Current Glau Prac 2013;7(1):19-24. PMID- 26997778 TI - Laser Treatment to avoid Trabeculectomy and to recover the Aqueous Outflow after Iris Incarceration in a Patient with NPDS. AB - The advantages of the nonpenetrating deep sclerectomy (NPDS) compared with the trabeculectomy are based on faster recovery and lower incidence of complications. The incarceration of the iris at the trabeculo-Descemet's membrane is one complication of NPDS and leads frequently to the reoperation of the patient. We report one case operated of NPDS with iris incarceration post-Nd:YAG goniopuncture in which we also documented spontaneous returning of the prolapsed iris during gonioscopy 3 hours after the onset of symptoms. With an argon laser iridoplasty, the iris returned completely to its position and a wide Nd:YAG laser iridotomy prevented recurrences. After this episode, the patient have always had intraocular pressure measures lower than 15 mm Hg. How to cite this article: Perez AV, Arenas JL, La Camara Hermoso JD. Laser Treatment to avoid Trabeculectomy and to recover the Aqueous Outflow after Iris Incarceration in a Patient with NPDS. J Current Glau Prac 2013;7(1):36-37. PMID- 26997779 TI - Editorial. PMID- 26997777 TI - Molecular Diagnostics and Genetic Counseling in Primary Congenital Glaucoma. AB - Primary congenital glaucoma (PCG) is a childhood irreversible blinding disorder with onset at birth or in the first year of life. It is characterized by the classical traid of symptoms viz. epiphora (excessive tearing), photophobia (hypersensitivity to light) and blepharospasm (inflammation of eyelids). The only anatomical defect seen in PCG is trabecular meshwork dysgenesis. PCG shows autosomal recessive mode of inheritance with considerable number of sporadic cases. The etiology of this disease has not been fully understood but some genes like CYP1B1, MYOC, FOXC1, LTBP2 have been implicated. Various chromosomal aberrations and mutations in mitochondrial genome have also been reported. Molecular biology has developed novel techniques in order to do genetic and biochemical characterization of many genetic disorders including PCG. Techniques like polymerase chain reaction, single strand conformational polymorphism and sequencing are already in use for diagnosis of PCG and other techniques like protein truncation testing and functional genomics are beginning to find their way into molecular workout of this disorder. In the light of its genetic etiology, it is important to develop methods for genetic counseling for the patients and their families so as to bring down its incidence. In this review, we ought to develop a genetic insight into PCG with possible use of molecular biology and functional genomics in understanding the disease etiology, pathogenesis, pathology and mechanism of inheritance. We will also discuss the possibilities and use of genetic counseling in this disease. How to cite this article: Faiq M, Mohanty K, Dada R, Dada T. Molecular Diagnostics and Genetic Counseling in Primary Congenital Glaucoma. J Current Glau Prac 2013;7(1):25-35. PMID- 26997780 TI - Pattern Electroretinography Changes in Patients with Established or Suspected Primary Open Angle Glaucoma. AB - PURPOSE: To assess pattern electroretinogram (PERG) changes in patients with established or suspected primary open angle glaucoma (POAG). MATERIALS AND METHODS: Transient PERG using LV Prasad eye electrodes were performed in 76 normal, 32 glaucomatous and 22 glaucoma suspect eyes. The P50 amplitude, N95 amplitude and P50 latency were analyzed. The results were further analyzed with receiver operating characteristic (ROC) curves and discriminant function analysis (DFA). RESULTS: The P50 and N95 amplitude of the POAG and glaucoma suspect groups were significantly reduced. There was significant shortening in the P50 latency in the POAG and glaucoma suspect groups. DFA using the P50 amplitude, N95 amplitude and P50 latency waveform parameters showed a sensitivity and specificity of 76.67 and 88.57% respectively. CONCLUSION: Pattern ERG demonstrated significant changes in POAG patients and suspects. ROC curves for the three wave parameters demonstrated that N95 amplitude was the better indicator for diagnosis of POAG when used individually. How to cite this article: Ganekal S, Dorairaj S, Jhanji V. Pattern Electroretinography Changes in Patients with Established or Suspected Primary Open Angle Glaucoma. J Current Glau Prac 2013;7(2):39-42. PMID- 26997781 TI - Manual Small Incision Cataract Surgery in Phacomorphic Glaucoma: Surgical Technique and Outcome in North-eastern India. AB - BACKGROUND: North-eastern region of India continue to suffer from limited resources, added upon by Mongoloid racial similarity and poor cataract surgery rate has contributed to the increase incidence of advanced cataract like phacomorphic glaucoma. OBJECTIVE: To evaluate the visual prognosis and related complications of phacomorphic glaucoma cases by manual small incision cataract surgeries in North-eastern region of India. MATERIALS AND METHODS: This retrospective case series study includes 65 phacomorphic glaucoma cases diagnosed between June 2009 to December 2011 in Jawaharlal Nehru Institute of Medical Sciences, Manipur. Preoperative routine evaluation includes slit-lamp biomicroscopy, measurement of IOP, gonioscopy of fellow eye, axial length measurement, AC depth and lens thickness by A-scan. Manual small incision cataract surgery with intraocular lens implantation was performed in all the 65 eyes. Complete ophthalmic examination was done at each follow-up visit. RESULTS: The mean preoperative IOP was 35.14 (+/-6.35) mm Hg and IOP at the 3rd month follow-up was 18.65 (+/-1.3) mm Hg with a statistically significant lowering of IOP (p < 0.0001) at the last follow-up. Intraoperative complications were minimal. Corneal edema, fibrinous exudates in AC was seen in few cases. Postoperative best corrected visual acuity was 6/6-6/12 in 46 eyes, 6/18-6/36 in 12 eyes, 6/60-3/60 in 4 eyes and less than 3/60 in three eyes. Antiglaucoma medication was discontinued immediately after each surgery. CONCLUSION: Manual small incision cataract surgery being inexpensive play a key role in management of poor outreach program marker like phacomorphic glaucoma in effectively controlling the IOP and achieving good visual acuity with minimal complications. How to cite this article: Rajkumari V, Kaminibabu KS, Bhabanisana RD, Victor R. Manual Small Incision Cataract Surgery in Phacomorphic Glaucoma: Surgical Technique and Outcome in North-eastern India. J Current Glau Prac 2013; 7(2):43 48. PMID- 26997782 TI - Current Concepts in the Biochemical Mechanisms of Glaucomatous Neurodegeneration. AB - Glaucoma is now regarded as a neurodegenerative disorder. A number of theories including the mechanical and vascular models have been used to explain the pathogenesis of glaucoma. However, there is now increasing evidence of biochemical molecules which may play a part in it's causation. These biochemical mechanisms include the role of excitatory aminoacids, caspases, protein kinases, oxygen free radicals, nitric oxide, TNF-alpha, neurotrophins and metalloproteins. This paper reviews these new developments which form the biochemical basis of glaucomatous neural degeneration. How to cite this article: Ahmad SS, Ghani SA, Rajagopal TH. Current Concepts in the Biochemical Mechanisms of Glaucomatous Neurodegeneration. J Current Glau Prac 2013;7(2):49-53. PMID- 26997783 TI - Premium IOLs in Glaucoma. AB - Advanced technology or premium intraocular lenses have been developed to meet the patient expectations of perfect distance and near vision without the need for spectacles. Careful patient selection is critical when implanting these implants. This brief review focusses mainly on multifocal and toric IOLs and their application and limitations in patients with glaucoma. How to cite this article: Ichhpujani P, Bhartiya S, Sharma A. Premium IOLs in Glaucoma. J Current Glau Prac 2013;7(2): 54-57. PMID- 26997786 TI - Imaging of Ocular Angle Structures with Fourier Domain Optical Coherence Tomography. AB - BACKGROUND: Imaging of the Schlemm's Canal is complicated by the small physiological size and the location several hundred microns beneath the sclera. Noninvasive imaging of Schlemm's canal and Trabecular Meshwork (TM) in vivo with Fourier Domain Optical Coherence Tomography (FD OCT) can provide clinicians with a powerful tool to visualize ocular angular structures crucial for glaucoma management. PURPOSE: To investigate the appearance of Schlemm's canal and TM on FD OCT images. METHODS: FD OCT images of the Schlemm's canal and TM were obtained with three different wavelengths using prototype FD OCT systems in a normal volunteer. FD OCT images using the 1310 nm wavelength prototype were obtained in three representative cases of glaucoma surgery performed on angle structures. RESULTS: The longer imaging depth and deeper tissue penetration of the 1310 nm system provided the clearest image of the TM and Schlemm's canal in the normal patient. In case 1, images pre- and post-trabectome surgery clearly showed the location and appearance of TM. In case 2, images post-canaloplasty surgery showed the location and appearance of Schlemm's canal. In case 3, images pre- and post trabeculotomy surgery further confirms the appearance and location of the Schlemm's canal and TM. CONCLUSION: Operating wavelength of the FD OCT system and exact location of the scan across different meridians minimally affects the appearance of the ocular anatomy. The postoperative images of three angle glaucoma surgeries confirmed the location of Schlemm's canal and TM. How to cite this article: Asrani S, Young M, Xu J, Sarunic MV. Imaging of Ocular Angle Structures with Fourier Domain Optical Coherence Tomography. J Current Glau Prac 2013;7(2):85-87. PMID- 26997784 TI - Selective Laser Trabeculoplasty: A Clinical Review. AB - Selective laser trabeculoplasty (SLT) is a safe and effective treatment modality for lowering the intraocular pressure in patients with glaucoma. It achieves its results by selective absorption of energy in the trabecular pigmented cells, sparing adjacent cells and tissues from thermal damage, with minimal morphological tissue alteration following treatment. On the basis of the peer reviewed medical literature, SLT is efficacious in lowering IOP, as initial treatment or when medical therapy is insufficient in all types of open-angle glaucoma in all races. SLT achieves intraocular pressure reduction similar to that of argon laser trabeculoplasty but without the tissue destruction and side effects. Observed side effects following SLT were almost uniformly transient and minor. We review highlights of recently published studies on the mechanisms and clinical outcome of SLT in order to address frequently raised issues pertinent to SLT in the clinical practice. KEY MESSAGES: Selective laser trabeculoplasty is a safe and effective treatment modality for lowering the intraocular pressure in patients with glaucoma. How to cite this article: Alon S. Selective Laser Trabeculoplasty: A Clinical Review. J Current Glau Prac 2013; 7(2):58-65. PMID- 26997787 TI - Evaluation of the Van Herick Technique for Screening for Occludable Angles in an African Population. AB - The current gold standard for screening for angle closure and adopting universal approaches to prophylaxis is the assessment of the anterior chamber (AC) angle by gonioscopy, a technique that has substantial interobserver variability and relies on subjective assessment. Slit-lamp estimation of the peripheral anterior chamber depth (ACD) by the Van Herick technique is a noncontact approach for estimating angle width and various authors have commented on its sensitivity and specificity as a screening tool for identifying narrow angles as well as angle closure.This case series draws attention to the fact that as many as 28 out of 36 (77.78%) seemingly open angles on Van Herick test were found to be potentially occludable angles on gonioscopy. Therefore, it may be concluded that gonioscopy is essential even in patients with deep peripheral ACs, before an occludable angle can be ruled out. How to cite this article: Bhartiya S, Shaarawy T. Evaluation of the Van Herick Technique for Screening for Occludable Angles in an African Population. J Current Glau Prac 2013;7(2):88-90. PMID- 26997788 TI - An Overlap Syndrome of Pigment Dispersion and Pigmentary Glaucoma accompanied by Marfan Syndrome: Case Report with Literature Review. AB - 'Overlap syndrome' describes the situation in which two or more 'independent' conditions are present, either one of which could cause a particular finding. This current presentation reports a case with bilateral pigment dispersion syndrome (PDS), advanced pigmentary glaucoma (PG), and the Marfan syndrome, with bilateral subluxation of the lenses, and large short-term and long-term fluctuations of intraocular pressure. It is interesting to consider whether the associated advanced glaucomatous nerve damage could be a manifestation of just the PDS, just the Marfan syndrome, or rather a combination of these two overlapping independent conditions. How to cite this article: Chakravarti T, George S. An Overlap Syndrome of Pigment Dispersion and Pigmentary Glaucoma accompanied by Marfan Syndrome: Case Report with Literature Review. J Current Glau Prac 2013;7(2):91-95. PMID- 26997789 TI - Editorial. PMID- 26997785 TI - Genetic, Biochemical and Clinical Insights into Primary Congenital Glaucoma. AB - Glaucoma is an irreversible form of optic neuropathy in which the optic nerve suffers damage in a characteristic manner with optic nerve cupping and retinal ganglion cell death. Primary congenital glaucoma (PCG) is an idiopathic irreversible childhood blinding disorder which manifests at birth or within the first year of life. PCG presents with a classical triad of symptoms (viz epiphora, photophobia and blepharospasm) though there are many additional symptoms, including large eye ball and hazy cornea. The only anatomical anomaly found in PCG is trabecular meshwork (TM) dysgenesis. PCG is an inheritable disease with established genetic etiology. It transmits through autosomal recessive mode. A number of cases are sporadic also. Mutations in many genes have been found to be causative in PCG and many are yet to be found. Mutations in cytochrome P4501B1 (CYP1B1) gene have been found to be the predominant cause of PCG. Other genes that have been implicated in PCG etiology are myocilin, Forkhead related transcription factor C1 (FOXC1) and latent transforming growth factor beta-binding protein 2 (LTBP2). Mutations in these genes have been reported from many parts of the world. In addition to this, mitochondrial genome mutations are also thought to be involved in its pathogenesis. There appears to be some mechanism involving more than one genetic factor. In this review, we will discuss the various clinical, biochemical and genetic aspects of PCG. We emphasize that etiology of PCG does not lie in a single gene or genetic factor. Research needs to be oriented into a direction where gene-gene interactions, ocular embryology, ophthalmic metabolism and systemic oxidative status need to be studied in order to understand this disorder. We also accentuate the need for ophthalmic genetic facilities in all ophthalmology setups. How to cite this article: Faiq M, Sharma R, Dada R, Mohanty K, Saluja D, Dada T. Genetic, Biochemical and Clinical Insights into Primary Congenital Glaucoma. J Current Glau Prac 2013;7(2):66-84. PMID- 26997790 TI - Cataract Surgery in the Glaucoma Patient: Beyond Intraocular Pressure. AB - How to cite this article: Singh K. Cataract Surgery in the Glaucoma Patient: Beyond Intraocular Pressure. J Current Glau Prac 2013;7(3):97-98. PMID- 26997791 TI - Cataract Surgery in Eyes with Previous Glaucoma Surgery: Pearls and Pitfalls. AB - The problem of cataract management in the patients of glaucoma who have undergone fltering surgery is a challenging proposition for any surgeon, as the surgery can lead to several complications in the already compromised eye. As glaucoma requires lifelong management, the development of cataract is a significant concern because its treatment may lead to loss of intraocular pressure (IOP) control. This review aims to highlight the intra- and postoperative measures that may increase the chances of bleb survival following cataract surgery. How to cite this article: Dada T, Bhartiya S, Baig NB. Cataract Surgery in Eyes with Previous Glaucoma Surgery: Pearls and Pitfalls. J Current Glau Prac 2013;7(3):99-105. PMID- 26997792 TI - Evaluation of the Optic Nerve Head in Glaucoma. AB - Glaucoma is an optic neuropathy leading to changes in the intrapaillary and parapaillary regions of the optic disk. Despite technological advances, clinical identification of optic nerve head characteristics remains the first step in diagnosis. Careful examination of the disk parameters including size, shape, neuroretinal rim shape and pallor; size of the optic cup in relation to the area of the disk; configuration and depth of the optic cup; ratios of cup-to-disk diameter and cup-to-disk area; presence and location of splinter-shaped hemorrhages; occurrence, size, configuration, and location of parapapillary chorioretinal atrophy; and visibility of the retinal nerve fiber layer (RNFL) is important to differentiate between the glaucomatous and nonglaucomatous optic neuropathy. How to cite this article: Gandhi M, Dubey S. Evaluation of the Optic Nerve Head in Glaucoma. J Current Glau Prac 2013;7(3):106-114. PMID- 26997793 TI - Pediatric Uveitic Glaucoma. AB - The pediatric glaucomas present some of the greatest clinical challenges. Uveitic glaucoma is a pathology whose causes and treatment are still a great enigma to all glaucoma specialists. We describe the spectrum of pediatric uveitic glaucoma along with its risk factors and the outcome of treatment in this subgroup. Our paper aims to review the existing literature on the subject and throw light on how to manage these cases. How to cite this article: Kaur S, Kaushik S, Pandav SS. Pediatric Uveitic Glaucoma. J Current Glau Prac 2013;7(3): 115-117. PMID- 26997794 TI - Pseudoexfoliation Syndrome. AB - Pseudoexfoliation (PXF) syndrome is a well-recognized clinical entity of considerable clinical significance. It is associated with poor mydriasis, cataracts with weak zonular support, secondary glaucoma and possibly with biochemical abnormalities, such as elevated homocysteine and systemic diseases involving the cardiovascular and central nervous system. There have also been some recent studies identifying mutations in genes which are associated with PXF. How to cite this article: Ariga M, Nivean M, Utkarsha P. Pseudoexfoliation Syndrome. J Current Glau Prac 2013;7(3): 118-120. PMID- 26997795 TI - Surgical Decisions in Primary Open Angle Glaucoma with Low or Normal Tension. AB - Glaucoma, given its insidious nature, is often coined 'the sneak thief of sight'. Following this trail of thought, primary open angle glaucoma with low or normal tension (POAGLNT) could be coined 'the king of thieves'. The lack of a compelling red fag of high intraocular pressure (IOP), together with the diurnal fuctuation of the deceptively low baseline IOP, POAGLNT poses a therapeutic challenge in terms of judging when to intervene, and how. In this review article, we will outline the considerations before undergoing surgery: risk stratification, defining goal in terms of target pressure and IOP modulation. We will also review the strengths, weaknesses and pearls of available options. How to cite this article: Shum JW, Leung DY. Surgical Decisions in Primary Open Angle Glaucoma with Low or Normal Tension. J Current Glau Prac 2013;7(3):121-127. PMID- 26997796 TI - How to Choose a Mentor? AB - Mentorship programs have been found to be of great use in all career fields, especially medicine. Given that the practice of medicine is best learnt by a hands-on training, a mentorship program can prove invaluable for the young clinician scientist. A structured super-speciality training program can help in both, acquisition of clinical and research skills, as well as career growth. How to cite this article: Bhartiya S, Ichhpujani P. How to Choose a Mentor? J Current Glau Prac 2013;7(3):128-129. PMID- 26997797 TI - Results of a New Technique for Implantation of Nonrestrictive Glaucoma Devices. AB - OBJECTIVE: To describe and present results of an original technique for nonvalved glaucoma implants. PATIENTS AND METHODS: Thirty-five eyes of 34 patients with aggressive and/or advanced glaucomas of different causes were included. A Baerveldt implant was used in all cases, using an absorbable ligature that had been titrated to allow fow from day 1, but avoiding hypotony. Intraocular pressure (IOP) during the first 8 weeks, final IOP, visual acuity and complications were analyzed. RESULTS: Mean preoperative IOP was 42.8 mm Hg (range: 24-64 mm Hg). IOP was 14.4, 17.2, 18.6, 19 and 16.4 mm Hg during the 1, 2, 4, 6 and 8 postoperative weeks. Mean final IOP was 13.8 +/- 4.25 mm Hg, a 67.8% reduction, after a mean follow-up time of 13 months (range: 8-29 months). Twenty-nine eyes (82.9%) had complete success, two had qualifed success (5.7%) and four were failures (11.4%). Choroidal detachments and transient tube obstructions were the most frequent complications. CONCLUSION: Titrated ligature of Baerveldt tubes was effective for controlling IOP during both the early and late postoperative phases in eyes with severe glaucomas. How to cite this article: Arismendi GEO, del Pilar Pena Valderrama C, Albis-Donado O. RESULTS of a New Technique for Implantation of Nonrestrictive Glaucoma Devices. J Current Glau Prac 2013;7(3):130-135. PMID- 26997798 TI - Editorial. PMID- 26997800 TI - Comparison of Treated Mean Intraocular Pressure in Stable Glaucoma with Different Severity in Vietnam. AB - PURPOSE: To compare stable glaucoma with different severity in a Vietnamese population in regard to mean intraocular pressure (IOP) and number of medications used. MATERIALS AND METHODS: A total of 116 eyes from 68 patients with medically treated glaucoma were prospectively enrolled at a single center and subjected to automated perimetry every 3 months for at least 9 months. Glaucoma progression was identifed according to early manifest glaucoma trial criterion using glaucoma progression analysis software. Eyes in which no progression was identifed were staged for glaucoma severity using field criteria (mild MD >= 6 dB, moderate MD 6 to -12 dB, advanced MD >= 12 dB, end-stage central island only). Groups were compared in terms of mean IOP and number of medications used. Statistical analysis was performed using SPSS v16.0. RESULTS: A total of 109 eyes displayed no evidence of pro gres-sion during the study period. Pretreatment mean IOP for mild, moderate, severe and end-stage glaucoma was 28.2 +/- 1.4, 28.8 +/- 1.6, 29.1 +/- 1.8, and 28.6 +/- 0.8 mm Hg. The mean IOP of all 109 eyes during follow up was 16.8 +/- 1.4 mm Hg (95% conf dence interval = 15.4 +/- 18.2 mm Hg). Mild, moderate, advan ced, and end-stage glaucoma had mean IOP of 17.5 +/- 1.2, 16.9 +/ 1.3, 15.8 +/- 0.9 and 15.5 +/- 1.1 mm Hg. The mean IOP of mild stage was significantly higher than advanced and end-stage (t-test, p < 0.001). Also, the mean IOP of moderate glaucoma was significantly higher than advanced and end stage glaucoma (t-test, p < 0.05). Number of medications had no signi ficant difference among these glaucoma stages (chi-square test, p > 0.05). CONCLUSION: Reached IOP lowering contributes to glaucoma stabilization especially in late stages. To maintain stable glaucoma, there was no difference in medical procedure of glaucoma stages. How to cite this article: Thanh NTH. Comparison of Treated Mean Intraocular Pressure in Stable Glaucoma with Different Severity in Vietnam. J Current Glau Prac 2014;8(1):7-9. PMID- 26997799 TI - Anterior Segment Optical Coherence Tomography Changes to the Anterior Chamber Angle in the Short-term following Laser Peripheral Iridoplasty. AB - PURPOSE: To evaluate, by anterior segment optical coherence tomography (AS-OCT), the changes in the anterior chamber angle during the short-term postoperative period after diode laser peripheral iridoplasty (LPI). METHODS: Retrospective, observational study of consecutive primary angle closure suspect, primary angle closure, or primary angle closure glaucoma patients who underwent LPI. These patients had persistent iridotrabecular contact despite the presence of a patent peripheral iridotomy. The AS-OCT images of the temporal and nasal anterior chamber angles in dark conditions before and after LPI were ana lyzed. The main outcome measures were changed in AS-OCT parameters such as trabecular-iris angle (TIA), angle opening distance (AOD), trabecular-iris space area (TISA), trabecular-iris contact length (TICL), iris thickness (IT), and maximum iris bow height (MIBH). Secondary outcome para meters included intraocular pressure (IOP) and postlaser complications. RESULTS: Images of 14 eyes of 14 patients were assessed. The mean time from LPI to the follow-up AS-OCT scan was 6 +/- 3 weeks. The IT did not alter significantly after LPI, but there were significant increases in the TIA, AOD and TISA, as well as a significant decrease in TICL and MIBH. There were no significant postlaser complications. There was a small decrease in mean IOP from 17.1 +/- 4.0 mm Hg to 14.8 +/- 4.6 mm Hg (p = 0.014). CONCLUSION: Based on AS-OCT imaging, LPI resulted in significant angle widening and iris profile fattening during the short-term postoperative period in eyes with persistent angle closure despite the presence of a patent peripheral iridotomy. How to cite this article: Leong JCY, O'Connor J, Ang GS, Wells AP. Anterior Segment Optical Coherence Tomography Changes to the Anterior Chamber Angle in the Short-term following Laser Peripheral Iridoplasty. J Current Glau Prac 2014;8(1):1-6. PMID- 26997801 TI - Macular Thickness Variability in Primary Open Angle Glaucoma Patients using Optical Coherence Tomography. AB - AIM: To compare the difference of retinal macular thickness and macular volume using optical coherence tomography (OCT) in primary open angle glaucoma (POAG) patients with the normal subjects. MATERIALS AND METHODS: This observational case control study included primary open angle glaucoma (POAG) patients (n = 124 eyes) and healthy subjects in the control group (n = 124 eyes). All subjects underwent detailed history, general and systemic exami -nation. Complete ocular examination included best corrected visual acuity (BCVA), slit lamp examination, intraocular pressure (IOP), central corneal thickness, gonioscopy, dilated fundus biomicroscopy. Field analysis was done by white on white Humphrey Field Analyzer (Carl Zeiss). Optical coherence tomography imaging of macular area was performed using Stratus OCT (OCT 3, Version 4, Carl Zeiss Inc, Dublin, California, USA). In both these groups, parameters analyzed were macular thickness, inner macular thicknesses (IMT), outer macular thicknesses (OMT), central macular thick ness (CMT) and total macular volume (TMV). RESULTS: The POAG group had significantly decreased values of TMV, OMT and IMT, compared to control group, while there was no difference in CMT, presumably due to absence of ganglion cells in the central part. Thus, macular thickness and volume parameters may be used for making the diagnosis of glaucoma especially in patients with abnormalities of disc. CONCLUSION: Macular thickness parameters correlated well with the diagnosis of glaucoma. How to cite this article: Sharma A, Agarwal P, Sathyan P, Saini VK. Macular Thickness Variability in Primary Open Angle Glaucoma Patients using Optical Coherence Tomography. J Current Glau Prac 2014;8(1):10-14. PMID- 26997802 TI - Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid induced Glaucoma. AB - PURPOSE: To evaluate the effect of 0.125% verapamil and 0.5% diltiazem eye drops on intraocular pressure (IOP) in steroid-induced glaucoma in rabbit eyes. METHODS: A total of 18 rabbits with steroid-induced glaucoma were divided into three groups (A, B and C; n = 6 each). Right eyes in groups A, B and C received 0.5% diltiazem, 0.125% verapamil and 0.5% timolol eye drops twice daily for 12 days, respectively; whereas, left eyes received distilled water. IOP was measured with Tono-pen XL at baseline, day 4, day 8, and day 12 of treatment. RESULTS: Both 0.5% diltiazem and 0.125% verapamil eye drops significantly reduced IOP compared to control eyes (p < 0.05). Reduction of IOP by 0.5% diltiazem, 0.125% verapamil eye drops were comparable to 0.5% timolol. No surface toxicity or systemic side effects were noted during the study period. CONCLUSION: Calcium channel blockers, verapamil, and diltia-zem significantly reduced IOP in rabbiteyes. This group of drugs may have a potential role in treatment of glaucoma How to cite this article: Ganekal S, Dorairaj S, Jhanji V, Kudlu K. Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid induced Glaucoma. J Current Glau Prac 2014;8(1):15-19. PMID- 26997803 TI - Early Postoperative Results and Complications of using the EX-PRESS Shunt in uncontrolled Uveitic Glaucoma: A Case Series of Preliminary Results. AB - PURPOSE: The purpose of this case series is to describe the efficacy of the EX PRESS shunt in uveitic glaucoma. METHODS: This prospective case series sequentially recruited uveitic glaucoma subjects with intraocular pressure (IOP) > 21 mm Hg despite maximal topical antiglaucoma medications from July 2012 to July 2013 in Hong Kong. All subjects received a trabeculectomy with mitomycin C (MMC) and EX-PRESS shunt implantation. The primary outcome measures included preope-rative IOP and postoperative IOP on day 1, 1 week, 1 month, and every 3 months thereafter. The secondary outcome measures included postoperative complications and follow-up procedures, pre- and postoperative Snellen best corrected visual acuity and cup-disc ratio, as well as the number of antiglaucoma medication required. RESULTS: In a case series of five subjects with uncontrolled uveitic glaucoma, two had inactive anterior uveitis, and three had active panuveitis. The mean preoperative IOP was 35.4 +/- 12.6 mm Hg on 3.8 +/- 0.5 antiglaucoma eye drops. The mean day 1, 1 week and 1 month IOP's were 6.6 +/- 3.7 mm Hg, 7.2 +/- 3.2 mm Hg, and 12.6 +/- 8.2 mm Hg, respectively. One case required subconjunctival MMC injections postoperatively; two required conjunctival resuture for leakage; and two had early postoperative hypotony that resolved after oral prednisolone. At 6 months, the mean IOP was 13.2 +/- 4.6 mm Hg. Four out of five subjects had IOP < 21 mm Hg without medication, and all had IOP < 21 mm Hg with antiglaucoma medication. CONCLUSION: The EX-PRESS shunt demonstrates good IOP control with a propensity for hypotony in the early postoperative period in this small uveitic glaucoma series. How to cite this article: Lee JWY, Chan JCH, Qing L, Lai JSM. Early Postoperative RESULTS and Complications of using the EXPRESS Shunt in uncontrolled Uveitic Glaucoma: A Case Series of Preliminary RESULTS. J Current Glau Prac 2014;8(1):20-24. PMID- 26997804 TI - Management of Secondary Angle Closure Glaucoma. AB - Secondary angle closure glaucomas are a distinct entity from primary angle closure glaucoma (PACG). Unlike PACG, secondary angle closure glaucoma's have an identifable contributory factor/s for angle closure and obstruction of aqueous fow which is usually unrelieved by iridotomy. The treatment of each type of secondary angle closure glaucoma is varied, so identification of the primary cause aids in its effective management. How to cite this article: Annadurai P, Vijaya L. Management of Secondary Angle Closure Glaucoma. J Current Glau Prac 2014;8(1):25-32. PMID- 26997805 TI - Optic Disk Pit and Iridociliary Cyst Precipitating Angle Closure Glaucoma. AB - Primary angle closure glaucoma is usually a bilateral disease, though it may be asymmetrical. However, it is unusual to see advanced glaucoma in one eye and no disk damage in the other. We present a case of unilateral angle closure glaucoma complicated by an optic disk pit and iridociliary cysts. How to cite this article: Kaushik S, Ichhpujani P, Kaur S, Pandav SS. Optic Disk Pit and Iridociliary Cyst Precipitating Angle Closure Glaucoma. J Current Glau Prac 2014;8(1): 33-35. PMID- 26997806 TI - Editorial. PMID- 26997809 TI - Complementary and Alternate Management of Glaucoma: The Verdict so Far. AB - Complementary and alternative medicine deserves scientific scrutiny as patients with glaucoma often lose vision despite adequate medical or surgical treatment. Most glaucomatologists abstain from recommending alternative medicine as there is little evidence to support most of the recommendations for complementary and alternate management (CAM) use in glaucoma. Megavitamin supplementation has not been shown to have a long-term beneficial effect on glaucoma. In a glaucomatous eye, a very modest benefit of IOP-lowering may be offset by the temporary elevation in IOP that accompanies exercise. There is little evidence to support the use of special diets, acupuncture, relaxation techniques, or therapeutic touch for the treatment of glaucoma. Marijuana can have a profound lowering of IOP, but the low response rate, short half-life, and significant toxicity are strong indicators that it is not an appropriate therapeutic agent. Future research must be carried out to document the effect of CAM not only on IOP, but also on perimetric tests or other objective parameters, such as ocular blood fow and nerve fiber layer thickness. How to cite this article: Bhartiya S, Ichhpujani P. Complementary and Alternate Management of Glaucoma: The Verdict so Far. J Curr Glaucoma Pract 2014;8(2):54-57. PMID- 26997807 TI - Wound Healing Modulation in Glaucoma Filtration Surgery-Conventional Practices and New Perspectives: The Role of Antifibrotic Agents (Part I). AB - Glaucoma filtration surgery is regularly performed for the treatment of glaucoma and trabeculectomy is often regarded as the 'gold standard' glaucoma operation. The biggest risk of failure of the operation is bleb scarring. The advent of anti fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5FU) has vastly prolonged the longevity of the bleb, but concerns remain regarding the potential increase in postoperative complications. More selective therapeutic targets have therefore been explored. One of these is vascular endothelial growth factor (VEGF) inhibition. Vascular endothelial growth factor inhi bition has a role not only in sub conjunctival angiogenesis inhi bition but also it has direct anti fibrotic properties. Newer phar macological compounds and materials have also been developed in recent years in attempt to modulate the wound healing in different ways after glaucoma surgery. These include physical barriers to scarring and vehicles for sustained release of pharmacological agents, and early promising results have been demonstrated. This two-part review will provide a discussion of the application of anti-fibrotic agents in glaucoma filtration surgery and evaluate the newer agents that have been developed. How to cite this article: Fan Gaskin JC, Nguyen DQ, Ang GS, O'Connor J, Crowston JG. Wound Healing Modulation in Glaucoma Filtration Surgery-Conventional Practices and New Pers pectives: The Role of Antifibrotic Agents (Part I). J Curr Glaucoma Pract 2014;8(2):37-45. PMID- 26997808 TI - Wound Healing Modulation in Glaucoma Filtration Surgery- Conventional Practices and New Perspectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II). AB - Glaucoma filtration surgery is regularly performed for the treatment of glaucoma and trabeculectomy is often regarded as the 'gold standard' glaucoma operation. The biggest risk of failure of the operation is bleb scarring. The advent of antifibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5FU) has vastly prolonged the longevity of the bleb, but concerns remain regarding the potential increase in postoperative complications. More selective therapeutic targets have therefore been explored. One of these is vascular endothelial growth factor (VEGF) inhibition. VEGF inhibition has a role not only in subconjunctival angiogenesis inhibition but also it has direct anti-fibrotic properties. Newer pharmacological compounds and materials have also been developed in recent years in attempt to modulate the wound healing in different ways after glaucoma surgery. These include physical barriers to scarring and vehicles for sustained release of pharmacological agents, and early promising results have been demonstrated. This two-part review will provide a discussion of the application of anti-fibrotic agents in glaucoma filtration surgery and evaluate the newer agents that have been developed. How to cite this article: Fan Gaskin JC, Nguyen DQ, Ang GS, O'Connor J, Crowston JG. Wound Healing Modulation in Glau coma Filtration Surgery-Conventional Practices and New Pers pectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II). J Curr Glaucoma Pract 2014;8(2):46-53. PMID- 26997810 TI - Traumatic Glaucoma in Children. AB - Young patients are more prone to ocular trauma but most of the published studies describe complicated cataract as a result of trauma with its treatment modality. As a result, little is known about the different causes, common presenting signs and symptoms, visual outcomes, and most frequent management modalities of traumatic glaucoma in children. This review aims to study the demographical profile, presentation, management and outcome of traumatic glaucoma in children as well as the various factors associated with advanced glaucomatous changes. How to cite this article: Kaur S, Kaushik S, Pandav SS. Traumatic Glaucoma in Children. J Curr Glaucoma Pract 2014; 8(2):58-62. PMID- 26997811 TI - Bulbar Conjunctival and Tenon's Layer Thickness Measurement using Optical Coherence Tomography. AB - PURPOSE: Observations made during glaucoma filtering surgery (trabeculectomy) suggest variability in the thickness of the bulbar conjunctiva and Tenon's layers between individuals. We propose that this could infuence the final bleb morphology and function. We designed a pilot study to assess this using optical coherence tomography (OCT) to measure bulbar conjunctival and Tenon's layer thickness. MATERIALS AND METHODS: A total of 67 eyes of 48 individuals were scanned using an optovue Mode RT100 version 2.0 OCT machine. Cross-line CAM-L scans were taken and the com bined bulbar conjunctival and Tenon's layer thickness was measured 3 mm above the superior limbus. Conjunctival and Tenon's layers appeared as a hyper-refective section as opposed to the hypo refective underlying sclera. Measurements were taken using the inbuilt review software. RESULTS: The age ranged from 23 to 91 years. There were 20 mal e s and 28 females. The mean conjunctival and Tenon's layer thick ness was 393 +/- 67 microns (mean +/- SD) ranging from 194 to 573 microns. CONCLUSION: Optical coherence tomography conjunctival and Tenon's layer thickness measurements appear to vary significantly between individuals. We postulate that this could infuence the final bleb morphology and may predict the risk of bleb encapsulation and failure or thin avascular blebs. Further assessment could establish cut-offs on which patients should receive intraoperative antimetabolites and/or Tenon's layer excision. How to cite this article: Howlett J, Vahdani K, Rossiter J. Bulbar Conjunctival and Tenon's Layer Thickness Measurement using Optical Coherence Tomography. J Curr Glaucoma Pract 2014;8(2):63-66. PMID- 26997814 TI - Role of Laser Iridoplasty in the Management of Angle Closure Mechanisms other than Pupillary Block. AB - PURPOSE: To investigate the treatment outcomes of argon laser peripheral iridoplasty (ALPI) in angle closure mechanisms other than pupillary block. METHODS: We conducted a comprehensive chart review to evaluate consecutive patients who underwent ALPI due to unsuccessful laser iridotomy (whenever the angles remained occludable) between July 2009 and April-2012. An occludable angle was defined as the posterior trabecular meshwork not visible for <=180 degrees without indentation on dark room gonioscopy. Eyes with previous incisional surgery or more than 90 degrees of peripheral anterior synechiae were excluded. Main data collected were age, presence of glaucoma, pre- and postlaser intraocular pressure (IOP), angle-status, and underlying angle closure mechanism. Main outcomes were post ALPI angle widening on gonioscopy and magnitude of IOP reduction. RESULTS: A total of 41 eyes (27 patients) with persistent occlu-dable angles were initially included in the analysis, comprising approximately 14% of the 196 patients (321 eyes) that had under gone laser iridotomy during the predefined period. Among these cases, most common angle closure mechanisms were plateauiris (56%) and lens-induced component (34%). Patients with plateau iris were mostly women and younger than those with lens-induced component (p <= 0.03). A total of 35 eyes (23 patients) underwent ALPI (63% had glaucoma). Mean IOP was significantly reduced from 18. 2 +/- 4.7 to 14.6 +/- 3.8 (p < 0.01), with no significant difference between patients with plateau iris and lens-induced components (p = 0.22). Over 91% of these eyes showed nonoccludable angles following ALPI (follow-up of 11.8 +/- 3.3 months). CONCLUSION: In this series of middle-aged patients with occlu-dable angles, despite a patent iridotomy, ALPI was a useful procedure independent of the underlying mechanism, leading to angle widening and moderate IOP reduction in most cases. How to cite this article: Prado VG, Dorairaj S, Biteli LG, Sousa AKS, Moreno PAM, Lopes FS, Prata TS. Role of Laser Iridoplasty in the Management of Angle Closure Mechanisms other than Pupillary Block. J Curr Glaucoma Pract 2014;8(2):82-84. PMID- 26997815 TI - Editorial. PMID- 26997812 TI - Intraocular Pressure Control after Trabeculectomy, Phacotrabeculectomy and Phacoemulsification in a Hispanic Population. AB - PURPOSE: To compare the efficacy of different surgical strategies for intraocular pressure (IOP) control in Hispanic glaucoma patients with and without visually significant cataracts. DESIGN: Comparative retrospective consecutive case series. METHODS: The charts of 153 consecutive patients with primary open angle glaucoma who underwent either trabeculectomy alone (n = 51), phacotrabeculectomy (n = 51), or phacoemulsification alone (n = 51) were reviewed to compare IOP control, the number of glaucoma medications required postoperatively, and the inci dence of surgical complications. RESULTS: Preoperative IOP was 17.5 +/- 5.2 mm Hg in the trabe-culectomy group, 15.4 +/- 4.5 mm Hg in the phacotrabeculectomy group and 13.9 +/- 2.9 mm Hg in the phacoemulsification group (p < 0.001 for all comparisons). Mean IOP reduction from baseline was 4.2 +/- 6.9 (24.6%) for the trabeculectomy group, 2.9 +/- 5.0 (20.8%) for the phacotrabeculectomy group, and 0.9 +/- 3.4 (6.5%) for the phacoemulsification group (p = 0.009). The number of IOP-lowering medications required postoperatively decreased significantly in all three groups (p = 0.001). The rate of early and late postoperative complications was similar between the trabeculectomy and phacotrabeculectomy groups and less for the phacoemulsification group. CONCLUSION: Trabeculectomy and phacotrabeculectomy are both viable surgical options for managing open angle glau coma. Both resulted in similar rates of success, IOP reduction, decrease in use of IOP-lowering medications and post operative complication rates. Phacoemulsification alone had a lower success rate and greater need for postoperative IOP-lowering medications compared to trabeculectomy alone or phacotrabeculectomy. Phacoemulsification alone may be a reasonable option for patients with visually significant cataract and lower baseline IOP. How to cite this article: Jung JL, Isida-Llerandi CG, Lazcano-Gomez G, SooHoo JR, Kahook MY. Intraocular Pressure Control after Trabeculectomy, Phacotrabeculectomy and Phaco emulsification in a Hispanic Population. J Curr Glaucoma Pract 2014;8(2):67-74. PMID- 26997813 TI - Evaluation of Central Macular Thickness and Retinal Nerve Fiber Layer Thickness using Spectral Domain Optical Coherence Tomography in a Tertiary Care Hospital. AB - PURPOSE: To evaluate the normative data of macular thickness and retinal nerve fiber layer thickness (RNFL) among normal subjects using spectral domain optical coherence tomography (OCT). MATERIALS AND METHODS: Normal subjects presenting to a tertiary medical hospital were included in the study. All patient underwent clinical examination followed by study of macular thickness and RN FL thick ness by spectral domain Topc on OCT. The data was collected and analyzed for variations in gender and age. The data was also compared with available literature. RESULTS: Total numbers of patients enrolled in the study were 154 (308 eyes). Numbers of males were 79 (158 eyes) and numbers of females were 75 (150 eyes). The mean age among males was 42.67 +/- 12.15 years and mean age among females was 42.88 +/- 11.73 years. Overall the mean mac ular thickness (central 1 mm zone) with SD - OCT was 241.75 +/- 17.3 microns. The mean macular volume was 7.6 cu. mm +/- 0.33. On analysis of the RNFL thickness, we observed that the RNFL was thickest in the inferior quadrant (138.58) followed by superior (122.30) nasal (116.32) and temporal quadrant (73.04). Gender-wise comparison of the data revealed no statistically significant difference for age, macular thickness parameters, volume and RFNL values except outer temporal thickness among males and females. No age-related difference was noted in the above parameters. On comparison with available norma tive data from India and elsewhere, we found significant variations with different machines. CONCLUSION: The study is the first to provide normative data using SD-OCT from central India. The data from spectral domain OCT correlated well with the values obtained from similar studies with SD - OCT. Values obtained from time domain OCT machines are different and are not comparable. How to cite this article: Agarwal P, Saini VK, Gupta S, Sharma A. Evaluation of Central Macular Thickness and Retinal Nerve Fiber Layer Thickness using Spectral Domain Optical Coherence Tomography in a Tertiary Care Hospital. J Curr Glaucoma Pract 2014;8(2):75-81. PMID- 26997816 TI - Letter to the Editor. PMID- 26997817 TI - Surgical Outcome of Ahmed Valve Implantation in Mexican Patients with Neovascular Glaucoma. AB - PURPOSE: To describe clinical results of Ahmed glaucoma valve implantation in Mexican patients with neovascular glaucoma (NVG). MATERIALS AND METHODS: We reviewed records of 60 eyes of 60 patients with NVG who underwent Ahmed valve implantation, with a follow-up period of 1 year. We identified successful and failed cases and compared baseline and follow-up characteristics to identify possible differences between both groups. RESULTS: We classified 36 eyes (60%) as successful and 24 (40%) as failed cases. We found a significant difference in success rate in patients who had a hypertensive phase at any time during the follow-up period (OR = 5.15, CI = 1.49-20.15, p = 0.004). Patients in the success group showed a statistically significant decrease in the number of glaucoma medications 1 year after surgery (p <0.0001). We found a statistically significant difference in success rate in patients who had preoperative best corrected visual acuity (BCVA) better than logmar 0.70 (odds ratio 4.31, CI = 1.1 19.3, p = 0.03086). CONCLUSION: A hypertensive postoperative phase and a preoperative BCVA worse or equal to 20/100 seem to be risk factors for Ahmed valve surgical failure in patients with NVG. How to cite this article: Hernandez Oteyza A, Lazcano-Gomez G, Jimenez-Roman J, Hernandez-Garciadiego C. Surgical Outcome of Ahmed Valve Implantation in Mexican Patients with Neovascular Glaucoma. J Curr Glaucoma Pract 2014;8(3):86-90. PMID- 26997818 TI - Anterior Segment Optical Coherence Tomography Imaging of Filtering Blebs after Deep Sclerectomy with Esnoper-Clip Implant: One-year Follow-up. AB - PURPOSE: To describe the technique of deep sclerectomy with the new Esnoper Clip(r) implant, the clinical outcome and the anatomic characteristics of filtering blebs, using anterior segment optical coherence tomography (AS-OCT). METHODS: A prospective case-series study was conducted in five eyes (5 patients) with open angle glaucoma. The fornix-based deep sclerectomy with Esnoper-Clip(r) implant was done by the same surgeon. In one case, mitomycin C was used during surgery. All participants underwent a complete ophthalmic examination and AS-OCT (Visante(r)) preoperatively, then at each follow-up visit, at 1 day, 1 week, 1 month, 6 months and 1 year postoperatively. Scans were obtained through sagittal and transversal plans to the implant. RESULTS: Intraocular pressure (IOP) was significantly reduced (p < 0.05) from a mean preoperative value of 23.4 +/- 8.6 mm Hg (n = 3.8 glaucoma medications) to a postoperative value of 6.0 +/- 2.5 (n = 0), 10.6 +/- 5.4 (n = 0), 13 +/- 1.6 (n = 0.4), 12.4 +/- 2.1 (n = 0.2) and 14.4 +/- 1.5 (n = 0.2) at 1 day, 1 week, 1 month, 6 months and 1 year respectively. AS OCT allowed the visualization of the two plates of the implant (scleral and suprasciliary), the trabeculodescemetic membrane and the hyporeflective spaces in the bleb wall thickness and in suprascleral and suprachoroidal localizations. An immediate postoperative hypotony and an anteriorization of the implant associated to trabeculodescemetic membrane rupture, were detected, although without significant clinical repercussions. CONCLUSION: Our first five deep sclerectomy with Esnoper-Clip implantation analysis suggest an effective and well-tolerated method to reduce IOP. AS-OCT is a noninvasive imaging technique that allows the anatomic analysis of the drainage mechanisms after glaucoma surgery. How to cite this article: Vieira L, Noronha M, Lemos V, Reina M, Gomes T. Anterior Segment Optical Coherence Tomography Imaging of Filtering Blebs after Deep Sclerectomy with Esnoper-Clip Implant: One-year Follow-up. J Curr Glaucoma Pract 2014;8(3):91 95. PMID- 26997819 TI - The Early Postoperative Complications of Two Different Tube Ligation Methods in Baerveldt Implant Surgery. AB - OBJECTIVE: To investigate the early postoperative complications in two different tube ligation methods during the first 3 months in Baerveldt implant surgery. PARTICIPANTS: This study involved 157 eyes from 144 patients who underwent Baerveldt Implant Surgery at the Japanese Red Cross Medical Center, Tokyo, Japan. METHODS: Pre- and postoperative intraocular pressure (IOP), combined surgery, postoperative time-point of tube ligation release, and postoperative complications in two different tube ligation methods [absorbable ligation method using 8-0 polyglactin suture (group A) and nonabsorbable ligation method using 7 0 nylon suture (group B)] were retrospectively reviewed. RESULTS: After excluding eyes that had undergone combined trabeculectomy (26 eyes) and vitrectomy (2 eyes), eyes with previous tube surgery (22 eyes), and eyes that had undergone the stent method (1 eye), 30 of 28 patients in group A and 71 eyes of 71 patients in group B were found to fit the criteria of this study. The rate of successful surgical outcome was 80% in group A and 74.6% in group B (p = 0.705). During the 3 months postoperative, high IOP tended to occur more often in group B (67.6%) than in group A (46.7%) (p = 0.073), and ciliochoroidal detachment tended to occur more often in group A (10.0%) than group B (2.8%) (p = 0.154). CONCLUSION: The results of this study show that both ligation methods are effective, however, the selection of tube ligation method should be done in accordance with the different method-specific risks to which may occur. How to cite this article: Kawamorita S, Hamanaka T, Sakurai T. The Early Postoperative Complications of Two Different Tube Ligation METHODS in Baerveldt Implant Surgery. J Curr Glaucoma Pract 2014;8(3):96-100. PMID- 26997820 TI - Utility of Ganglion Cell Complex Analysis in Early Diagnosis and Monitoring of Glaucoma using a Different Spectral Domain Optical Coherence Tomography. AB - PURPOSE: To determine the importance of ganglion cell complex (GCC) analysis as a parameter for early diagnosis of glaucoma and for following glaucoma progression and to compare glaucoma progression with conventional visual field analysis using a different type of spectral-domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: Two hundred eyes including 68 normal eyes, 70 eyes with pre-perimetric glaucoma and 62 eyes with perimetric glaucoma were analyzed in this prospective study undertaken during Jan 2013 to Dec 2013 in a tertiary ophthalmology institute. Automated visual field examination was done to group the subjects in above three categories. The thicknesses of the GCC and retinal nerve fiber layer (pRNFL) were measured using Topcon model 2000 version 7.1 SD-OCT images and compared. The statistical analysis was carried out by z-test. RESULTS: The average GCC was thickest in the normal group and the thickness decreased as the severity of glaucoma increased. The mean macular GCC at the start and end of the study in pre-perimetric (94.86 +/- 8.31, 90.74 +/- 8.46) and perimetric (82.48 +/- 13.21, 79.80 +/- 12.88) eyes was lower than those in normals (102.70 +/- 7.19, 101.82 +/- 7.42). CONCLUSION: Majority of the studies done on GCC analysis have used the Cirrus OCT (Zeiss). Our study has used the Topcon model 2000 version 7.1 to show that irrespective of the machine used, GCC analysis definitely plays an important role. To detect pre-perimetric glaucoma and may show progression earlier than pRNFL in pre-perimetric glaucoma. How to cite this article: Bhagat PR, Deshpande KV, Natu B. Utility of Ganglion Cell Complex Analysis in Early Diagnosis and Monitoring of Glaucoma using a Different Spectral Domain Optical Coherence Tomography. J Curr Glaucoma Pract 2014;8(3):101-106. PMID- 26997821 TI - Screening First Degree Relatives of Persons with Primary Open Angle Glaucoma in India. AB - PURPOSE: To report the results of screening first degree relatives of persons identified with primary open angle glaucoma in a tertiary eye hospital glaucoma services. DESIGN: A cross-sectional study of first degree relatives of persons with primary open angle glaucoma. MATERIALS AND METHODS: First degree relatives of patients identified with primary open angle glaucoma were invited to participate in a screening evaluation in the base hospital to detect glaucoma. All participating individuals had comprehensive eye examination including vision screening, refraction, slit-lamp biomicroscopy, applanation tonometry, gonioscopy, frequency doubling peri-metry and dilated fundus examination. Persons with definite and suspected glaucoma were subject to full threshold automated perimetry. RESULTS: A 514 first degree relatives of 346 persons with primary open angle glaucoma, of 4972 individuals who were invited to participate attended the screening examination (Response Rate 7%). Fifty-five percent of those who attended were males and mean age of participants was 56.8 years. Sixty-eight relatives (13.3% of those screened) were detected to have definite glaucoma. Sixty percent of those detected with definite glaucoma were siblings. Fifteen percent of siblings, 4% of off-springs and 20% of parents who attended the screening examination had definite open angle glaucoma. CONCLUSION: Prevalence of open angle glaucoma amongst first degree relatives of persons with glaucoma is higher than in the general population as reported in previous studies. Significant barriers, however, exist in the uptake of eye care services among relatives of persons known to have primary open angle glaucoma. How to cite this article: Rajendrababu S, Gupta N, Vijayakumar B, Kumaragurupari R, Krishnadas SR. Screening First Degree Relatives of Persons with Primary Open Angle Glaucoma in India. J Curr Glaucoma Pract 2014;8(3):107-112. PMID- 26997823 TI - Editorial. PMID- 26997822 TI - Bilateral Acute Angle-closure after Intraocular Surgery. AB - We report the case of a 75-year-old woman who developed an acute bilateral angle closure associated with choroidal effusion a day after an uneventful cataract surgery. The same patient had undergone a similarly uneventful cataract surgery two weeks before, under the same protocol, with no postoperative complication in the other eye. Medical treatment, including the use of oral sulfamide-related drugs (acetazolamide), topical beta-blockers and steroids led to a gradual decrease in intraocular pressure (IOP) and choroidal effusion. Despite initial reports suggesting a link between sulfamide-exposure and these rare forms of angle-closure, our report would suggest a more complex pathophysiology behind this intriguing phenomenon. How to cite this article: Hoskens K, Pinto LA, Vandewalle E, Verdonk N, Stalmans I. Bilateral Acute Angle-closure after Intraocular Surgery. J Curr Glaucoma Pract 2014;8(3):113-114. PMID- 26997824 TI - Magnetic Resonance Imaging Study on Blebs Morphology of Ahmed Valves. AB - PURPOSE: To determine the morphometric parameters of filtration blebs of a valved aqueous humor drainage device. MATERIALS AND METHODS: Orbital magnetic resonances imaging (MRI) was taken after implantation of an Ahmed valve (FP7 model). Outcomes of the analysis were intraocular pressure (IOP) and the bleb's morphometric analysis (volume, height, major and minor axis). Associations between IOP and the imaging-related study variables were explored by Spearman's correlation test. RESULTS: Eleven patients underwent orbital MRI examination. Recordings were taken after a mean of 2.7 months (1-6 months) after surgery. IOP was significantly lower than its preoperative values (17.6 +/- 6.4 mm Hg vs 36.1 +/- 6.4 mm Hg, p < 0.01). Mean bleb volume was 856.9 +/- 261 mm(3) and its height, major and minor axis were 5.77 +/- 1.9, 14.8 +/- 2.9 and 8.14 +/- 3.6 mm, respectively. A positive correlation was detected between IOP and mean height (r = 0.77, p = 0.048) and major axis (r = 0.83, p = 0.03). Interestingly, the overall bleb volume was related to IOP levels immediately prior to surgery (r = 0.75, p < 0.01). Additionally, the posterior part of the plate was found to be displaced from the scleral surface in five cases (45%). CONCLUSION: Ahmed valve's bleb morphology seems to correlate with both the pre- and postoperative IOP, which might suggest a clinical benefit of administering aqueous suppressants pre- as well as postoperatively. The plate of the device may show a significant dislocation from its initial surgical implantation site. How to cite this article: Ferreira J, Fernandes F, Patricio M, Bras A, Rios C, Stalmans I, Pinto LA. Magnetic Resonance Imaging Study on Blebs Morphology of Ahmed Valves. J Curr Glaucoma Pract 2015;9(1):1-5. PMID- 26997825 TI - Achieving Target Pressures with Combined Surgery: Primary Patchless Ahmed Valve Combined with Phacoemulsification vs Primary Phacotrabeculectomy. AB - PURPOSE: To evaluate the ability of phacoemulsification combined with either primary trabeculectomy (PT) or primary Ahmed glaucoma valve implantation (PAVI) to achieve target intraocular pressures (TIOP) in adults with primary open angle glaucoma. MATERIALS AND METHODS: Chart review of 214 adult patients operated between January 2002 and June 2008 with a minimum follow-up of 6 months. Group 1 comprised 181 eyes of 166 patients undergoing PT while group 2 included 50 eyes of 49 patients in combination with primary AVI. Target lOPs were pre-determined for each patient and success was defined as an IOP at or lower than target with or without medications. An IOP above target, loss of light perception or need for additional procedures to lower IOP were considered a failure. RESULTS: Mean preoperative IOP was 17.2 mm Hg in group 1 and 17.3 in group 2. Mean postoperative IOPs were 10.2 and 9.2 on day 1, 12.2 and 11.6 at year 1, and 10.7 in both groups at year 5. Survival rates in groups 1 and 2 were 96.7 vs 96% at 6 months, 89 vs 96% at 12 months, 83.5 vs 96% at 24 months and 79.4 vs 89.1% at 36, 48 and 72 months. Transient bleb leaks were more frequent in group 1 (26 eyes, 14.4 vs 0%, p = 0.001) and transient choroidal detachments were more frequent in group 2 (7 eyes, 3.9 vs 6 eyes, 12%, p = 0.038). CONCLUSION: Midterm results for achieving target pressures using combined phacoemulsification with either PT or PAVI are comparable. The profile of complications is different for the two procedures. How to cite this article: Albis-Donado O, Sanchez-Noguera CC, Cardenas-Gomez L, Castaneda-Diez R, Thomas R, Gil-Carrasco F. Achieving Target Pressures with Combined Surgery: Primary Patchless Ahmed Valve Combined with Phacoemulsification vs Primary Phacotrabeculectomy. J Curr Glaucoma Pract 2015;9(1):6-11. PMID- 26997826 TI - Does Chronic Hypotony following Trabeculectomy Represent Treatment Failure? AB - PURPOSE: To measure the rate of complications from chronic hypotony following trabeculectomy and clarify the definition of postoperative hypotony. MATERIALS AND METHODS: In this retrospective case-control study, the rate of complications was compared between 34 eyes with chronic hypotony and 34 eyes without hypotony. Chronic hypotony was defined as those eyes with an intraocular pressure (IOP) of less than 6 mm Hg on two consecutive clinic visits at least 3 months after trabeculectomy. Cases were identified from a database of two glaucoma surgeons between 2010 and 2013. Outcomes measured included visual acuity, presence of choroidal effusion, hypotensive maculopathy and cataract development/progression. Factors associated with the development of hypotony were considered using analysis of variance (ANOVA) multivariate regression. RESULTS: Maculopathy was seen in 23.5% of hypotony eyes but not in controls (p < 0.01). No significant difference in the rate of choroidal effusion or cataract was documented between groups. Control eyes were more likely to remain complication free (58.8 vs 32.4%, p < 0.03). Spontaneous recovery from hypotony occurred in 32.4% of hypotony eyes. CONCLUSION: Sight threatening complications occur more frequently in eyes with chronic hypotony following glaucoma surgery. However, not all eyes with chronic hypotony develop sight threatening complications. A definition of hypotony that combines IOP criteria with the presence of structural and/or functional changes is recommended. How to cite this article: Yun S, Chua B, I Clement C. Does Chronic Hypotony following Trabeculectomy Represent Treatment Failure? J Curr Glaucoma Pract 2015;9(1):12-15. PMID- 26997827 TI - Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients. AB - PURPOSE: Glaucomatous neuropathy can be a consequence of insufficient blood supply, increase in intraocular pressure (IOP), or other risk factors that diminish the ocular blood flow. To determine the ocular perfusion pressure (OPP) in normal and systemic hypertensive patients. MATERIALS AND METHODS: One hundred and twenty-one patients were enrolled in this prospective and comparative study and underwent a complete ophthalmologic examination including slit lamp examination, Goldmann applanation tonometry, stereoscopic fundus examination, and pulsatile ocular blood flow (POBF) measurements. The OPP was calculated as being the medium systemic arterial pressure (MAP) less the IOP. Only right eye values were considered for calculations using Student's t-test. RESULTS: The mean age of the patients was 57.5 years (36-78), and 68.5% were women. There was a statistically significant difference in the OPP of the normal and systemic hypertensive patients (p < 0.05). The difference in the OPP between these groups varied between 8.84 and 17.9 mm Hg. CONCLUSION: The results of this study suggest that although the systemic hypertensive patients have a higher OPP in comparison to normal patients, this increase does not mean that they also have a higher OBF (as measured by POBF tonograph). This may be caused by chronic changes in the vascular network and in the blood hemodynamics in patients with systemic hypertension. How to cite this article: Kanadani FN, Figueiredo CR, Miranda RM, Cunha PLT, Kanadani TCM, Dorairaj S. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients. J Curr Glaucoma Pract 2015;9(1):16-19. PMID- 26997828 TI - Diurnal Intraocular Pressure Fluctuation in Eyes with Angle-closure. AB - PURPOSE: To investigate diurnal intraocular pressure (IOP) fluctuation in eyes with angle-closure. MATERIALS AND METHODS: Seventy-seven eyes of 77 newly diagnosed patients with angle closure [33 subjects with primary angle-closure suspects (PACS), 23 subjects with primary angle-closure (PAC), and 21 subjects with primary angle-closure glau-coma (PACG)] were enrolled after laser peripheral iridotomy for this prospective, cross-sectional study. Goldmann applanation tonometry (GAT) was performed at 08:00, 12:00, 16:00, 20:00, and 04:00 hours. Mean diurnal IOP, peak IOP, trough IOP, and IOP fluctuation (peak-trough) were compared between groups. RESULTS: The mean age of the enrolled subjects was 56.8 +/- 5.4 years, with 30 males and 47 females. Intraocular pressure fluctuation was significantly higher in the PACG (7.4 +/- 2.8 mm Hg) and PAC (5.5 +/- 2.3 mm Hg) groups compared with PACS subjects (4.4 +/- 1.5 mm Hg). The highest IOP was recorded at 04:00 hours in all but two patients. Two PACS, 10 PAC and 8 PACG patients, with normal office hour IOP had IOP peaks > 21 mm Hg at night. Twenty five percent patients (20/77) had abnormal IOP despite good office hour readings. CONCLUSION: Primary angle-closure glaucoma and PAC eyes showed diurnal IOP fluctuations greater than 5 mm Hg in most subjects, with peak IOP recorded at 04:00 hours. Peak IOP was higher than office hour IOP recordings in subjects with angle-closure. A diurnal variation curve is recommended in these subjects, especially in cases with controlled IOP during office hours. How to cite this article: Bhartiya S, Ichhpujani P. Diurnal Intraocular Pressure Fluctuation in Eyes with Angle-closure. J Curr Glaucoma Pract 2015;9(1):20-23. PMID- 26997829 TI - Biodegradable Collagen Implants in Trabeculectomy. AB - Subconjunctival and subscleral fibrosis are the major causes of failure of filtering surgery. Antiproliferative agents have been successfully used to improve the long-term success of this surgery. Recent advancement in the field of glaucoma surgery has been the use of bioengineered, biodegradable, porous collagen-glycosaminoglycan matrix implant in the subconjunctival and/or subscleral space to modify the wound-healing process and reduce scar formation, hence improving the surgical success without the need for anti-fibrotic agents. Biodegradable, collagen implants have shown favorable results when used with deep sclerectomy. There have been variable results regarding the success of trabeculectomy when combined with these implants. These implants also decrease the dose of mitomycin C required with trabeculectomy and hence, decrease the side effect associated with these drugs. The use of the biodegradable implants in glaucoma surgery is still evolving and further studies are needed to find the appropriate surgical technique, the ideal size and site of placement and determine their long-term impact on trabeculectomy outcomes and complications. How to cite this article: Ichhpujani P, Dada T, Bhartiya S. Biodegradable Collagen Implants in Trabeculectomy. J Curr Glaucoma Pract 2015;9(1):24-27. PMID- 26997831 TI - Editorial. PMID- 26997830 TI - Surgical Management of Iatrogenic Pigment Dispersion Glaucoma. AB - INTRODUCTION: Iatrogenic pigment dispersion syndrome generally originates from a repetitive, mechanical trauma to the pigmented posterior epithelium of the iris. This trauma can arise after intraocular surgery, most commonly due to an abnormal contact between the intraocular lens (IOL) and the iris. Whether surgical removal of this primary insult can lead to a successful intraocular pressure (IOP) control remains unclear. METHODS: Case-series. Patients with IOP elevation and clinical signs of pigment dispersion were screened for a diagnosis of iatrogenic IOL-related pigment dispersion. RESULTS: Three patients in which the IOL or the IOL-bag complex caused a pigment dispersion through a repetitive iris chafing were selected. In two cases, replacement of a sulcus-based single-piece IOL (patient 1) or a sub-luxated in-the-bag IOL (patient 2) by an anterior-chamber (AC) iris-fixed IOL led to a sustained decrease in IOP. In the third case, extensive iris atrophy and poor anatomical AC parameters for IOL implantation precluded further surgical intervention. CONCLUSION: IOL-exchange appears to be a useful tool in the management of iatrogenic pigment dispersion glaucoma due to inappropriate IOL implantation. This cause-oriented approach seems to be effective in controlling IOP, but should be offered only if safety criteria are met. How to cite this article: Van Mierlo C, Abegao Pinto L, Stalmans I. Surgical Management of Iatrogenic Pigment Dispersion Glaucoma. J Curr Glaucoma Pract 2015;9(1):28-32. PMID- 26997832 TI - How 'Drug Aware' are our Glaucoma Patients? AB - BACKGROUND: Poor knowledge, attitude and self-care practices (KAP) as regards medication compliance is a major concern in the management of glaucoma. This study aims to evaluate the knowledge, attitude regarding eyedrop instillation and self-care practices pertaining to eyedrops in diagnosed glaucoma patients. METHODS: In this cross-sectional, open-ended questionnaire-based study, 101 consecutive glaucoma patients on medication were recruited from an urban tertiary care hospital of North India. A self-designed 10-point KAP questionnaire that addressed patient-, medication-, environment- and physicians related factors was used. For each desirable answer, the participant gives a score of 1 was given and for each undesirable answer a score of '0' was given for each question. The total scores for each domain were calculated separately along with the total score. The association between the individual domain scores, the total score and various sociodemographic parameters were compared using unpaired t-test. Analysis of variance (ANOVA) test was used to compare the means, where the exposure variable had more than two categories. RESULTS: Out of 101 participants, 98% knew the reason why they were instilling the medicine. Only 61.4% subjects knew that the eyedrops should be stored in cool and dry place. Nearly 30% participants believed that two eyedrops could be instilled back to back. Half of the participants (55.4%) did not consider missing a dose of medicine to be significant. Majority (89.1%) of the participants asked the doctor about the drug dosage and timings and 71.3% of them did not use the eyedrops beyond 40 days after opening the vial. 37.6% participants believed that the medicine could be discontinued without asking the doctor, once the symptoms are relieved. Eighty percent patients checked the vial for correct drug name and expiry date before buying. 57.4% of the participants washed their hands before instilling the eyedrops. Only 23.8% patients asked their doctor for alternate medication name, in case they do not get the primary medication. There were no statistically significant differences in the mean domain and total scores between males and females and between urban and rural patients. There were no statistically significant differences in knowledge (p = 0.059) and attitude (p = 0.809) scores in people with different educational qualification. But education had a statistically significant relation with the practice scores (p = 0.004) and total scores (p = 0.047). CONCLUSION(S): There exists marked variation in the reported practices, even in the very basic prerequisites of instilling eye-drops like washing of hands, checking the expiry date before the usage of eyedrops. The findings in our study suggest a need to better educate our patients by providing them detailed information about eyedrop and its administration. This would help to reduce patients' frustration, improve compliance and increase the efficacy of anti-glaucoma therapy. How to cite this article: Mohindroo C, Ichhpujani P, Kumar S. How 'Drug Aware' are our Glaucoma Patients? J Curr Glaucoma Pract 2015;9(2):33-37. PMID- 26997833 TI - Strategies to Improve Glaucoma Compliance Based on Cross-Sectional Response-Based Data in a Tertiary Healthcare Center: The Glauco-Jung Study. AB - PURPOSE: To elucidate compliance rates among glaucoma patients in a tertiary healthcare center, reasons for noncompliance and response-based-solutions to improve compl iance in the same cohort. MATERIALS AND METHODS: In the Glauco-Jung study, a cross-sectional descriptive epidemiological one, information was obtained from 500 patients from 1st January, 2014 to 30th June, 2014. Patients were intercepted at entry point where they get their intraocular pressure (IOP) checked, wherein they were asked to fill an exhaustive questionnaire. At the same setting, they were also asked to demonstrate how they (or their relatives or helpers) instill eyedrops, following which any irregularities were brought to notice and corrected. Finally, they were also asked any suggestions to improve compliance to medications. Noncompliance rates were determined based on the number of patients who did not instill anti-glaucoma medications as per prescribed dosage or frequency schedule. Noncompliance rates were then evaluated by the Chi-square test for any association with distributions based on various parameters. RESULTS: In case of a positive association, correlation coefficient was further calculated to know the strength of this association. No association was observed in distributions based on diet, associated co-morbidities, daily dosage frequency and side-effects experienced by patients. Positive association was noted in distributions based on age, sex, duration of treatment, social structure and number of medications (p < 0.05); but correlation coefficients were very weak (c < 0.3). Cost of medications not only had positive association but also had a very strong correlation coefficient (c = 0.9188), proving that cost of medications had a modest bearing on compliance rates. CONCLUSION: The Glauco-Jung study concluded that besides availability of medications at reasonable cost, simplification of treatment regimen and interactive health education appear to be the most important factors for improving compliance so that patients do not feel guilty or inadequate because they have problems while administering their eyedrops. How to cite this article: Gupta VS, Sethi H, Naik M. Strategies to Improve Glaucoma Compliance Based on Cross-Sectional Response-Based Data in a Tertiary Healthcare Center: The Glauco-Jung Study. J Curr Glaucoma Pract 2015;9(2):38-46. PMID- 26997834 TI - Videographic Assessment of Glaucoma Drop Instillation. AB - PURPOSE: To assess the effect of patient education on videotaped topical instillation of artificial tear drops on subsequent topical instillation. MATERIALS AND METHODS: Forty-five patients, who had been using glaucoma drops for at least 6 months and with a best-corrected visual acuity of 20/100 or better, were studied. The patients were asked to instill an artificial tear drop using their accustomed technique while being video recorded. The patients viewed the recordings, and the errors in their drop instillation method were pointed out. This was followed by an educational session on proper drop instillation technique. After 30 minutes, patients were videotaped instilling drops to ascertain the effect of the educational session. The variables compared were: number of drops instilled, number of drops reaching the ocular surface, and the number of times the tip of the medication bottle touched the eye or ocular adnexa. RESULTS: Before the instruction session, patients squeezed an average of 1.5 +/- 0.9 drops from the bottle, and the average number of drops reaching the conjunctival fornix was 0.9 +/- 0.7. The tip of the bottle touched the ocular adnexa in 29/45 (64.4%) patients. After the education session, the patients squeezed an average of 1.2 +/- 0.5 drops and an average of 1.2 +/- 0.4 drops reached the conjunctival fornix. The tip of the bottle touched the ocular adnexa in 13/45 (28.9%) patients. With proper instructions, the percentage of patients that instilled just one drop on the eye increased from 66 to 82%. CONCLUSION: A single educational session on the proper use of topical drops improves the successful instillation of eye drops. However, it was not determined whether the patients will retain the improved instillation technique for long-term or if the intervention results in only a short-term improvement. How to cite this article: Lazcano-Gomez G, Castillejos A, Kahook M, Jimenez-Roman J, Gonzalez-Salinas R. Video-graphic Assessment of Glaucoma Drop Instillation. J Curr Glaucoma Pract 2015;9(2):47-50. PMID- 26997836 TI - New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case. AB - We present the case of successful repair of an exposed glaucoma drainage tube by cornea graft fixation with tissue adhesive, and without subsequent coverage by adjacent conjunctiva or donor tissues. Patient with history of keratoglobus with thin cornea and sclera, and phthisical contralateral eye, underwent three unsuccessful corneal grafts followed by Boston type 1 keratoprosthesis in the right eye. Ahmed drainage device with sclera patch graft was implanted to control the intraocular pressure. Two years later the tube eroded through sclera graft and conjunctiva. Repair was performed by covering the tube with a corneal patch graft secured by tissue adhesive after the conjunctiva in this area was dissected away. The cornea graft was left uncovered due to fragility of adjacent conjunctiva. The healing of ocular and graft surfaces was complete prior to the 1 month follow-up. Conjunctival epithelium covered the corneal patch graft. At 12 months follow-up, the graft and the tube remained stable. Our report suggests that corneal patch graft fixation to the sclera by means of tissue adhesive, without closing the conjunctiva, can be considered as an effective alternative surgical approach for managing exposed glaucoma drainage tube, accompanied by adjacent conjunctiva tissue deficiency. How to cite this article: Berezina TL, Fechtner RD, Cohen A, Kim EE, Chu DS. New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case. J Curr Glaucoma Pract 2015;9(2):62-64. PMID- 26997837 TI - Editorial. PMID- 26997838 TI - Suitability of the Visual Field Index according to Glaucoma Severity. AB - PURPOSE: To investigate the suitability of the visual field index (VFI) in different degrees of disease severity in glaucoma patients. METHODS: In this cross-sectional study, we consecutively enrolled patients with primary open-angle glaucoma and glaucoma suspects (ocular hypertension). All eyes required a reliable standard automated perimetry (SAP) test to be included. Subjects were categorized into five groups based on glaucoma severity using SAP's mean deviation (MD). To evaluate the correlation among VFI, MD and pattern standard deviation (PSD), a linear regression model was built. To evaluate the nature of the correlation (i.e. linear vs nonlinear), results were plotted in a scatterplot graph. RESULTS: One hundred and twenty-two eyes of 81 patients (mean age, 59.8 +/ 14.5 years) were included. A strong, positive association was found between MD and VFI values (R(2) = 0.98, p < 0.001), showing a 3.2% reduction in the VFI for each dB loss in the MD index. It was noticed that 15% of eyes with mild glaucoma (average MD of -3.1 dB) had VFI > 99%. Considering only the eyes with mild and moderate damage in the regression, we found a weaker (nonlinear) correlation than the one we found using all eyes (R(2) = 0.85, p < 0.001). There was also a significant, nonlinear correlation between VFI and PSD (R(2) = 0.85, p < 0.001). Although higher PSD values were found with increasing visual field damage, this initial trend was reversed when VFI became smaller than 50%, approximately. CONCLUSION: Visual field index had a strong correlation with MD; however, this correlation was weaker in mild disease, as some patients with early disease had very high VFI values (ceiling effect). Therefore, initial deterioration in visual field status (as assessed by MD values) in patients with early disease may not be detectable using the VFI alone. How to cite this article: Sousa MCC, Biteli LG, Dorairaj S, Maslin JS, Leite M, Prata TS. Suitability of the Visual Field Index according to Glaucoma Severity. J Curr Glaucoma Pract 2015;9(3):65-68. PMID- 26997835 TI - Surgery on the Trabecular Meshwork: Histopathological Evidence. AB - Juxtacanalicular (JXT) trabecular meshwork and endothelial lining of Schlemm's canal have been cited as the loci of aqueous outflow resistance, both in a normal as well as a glaucomatous eye. In this review, we attempt to understand the currently available surgical modalities in light of the available histopathological evidence, regarding localization of outflow resistance. How to cite this article: Bhartiya S, Ichhpujani P, Shaarawy T. Surgery on the Trabecular Meshwork: Histopathological Evidence. J Curr Glaucoma Pract 2015;9(2):51-61. PMID- 26997839 TI - Pigment Dispersion Syndrome Progression to Pigmentary Glaucoma in a Latin American Population. AB - OBJECTIVE: To determine the progression of pigment dispersion syndrome (PDS) into pigmentary glaucoma (PG) in a population at the Central Military Hospital in Bogota, Colombia. MATERIALS AND METHODS: A retrospective study was conducted, based on a review of medical records of patients with PDS evaluated in the Glaucoma Clinic. Data were collected in a database in excel and subsequently analyzed with the software Statistical Package for the Social Sciences (SPSS), performing Chi-square test analysis and Spearman's rho test. RESULTS: Forty-eight eyes of 24 patients were included. Forty-two percent were women and 58% were men. Pigmentation of the trabecular meshwork was the most frequent clinical sign (100%), followed by Krukenberg's spindle (91.7%), the least frequent were the iris concavity and iris heterochromia (4.2%), the average of the spherical equivalent was of - 1.33 (SD 2.07). The rate of conversion of PDS to PG was 37.5%, after an average follow-up of 50.7 months. Having an intraocular pressure (IOP) greater than 21 mm Hg was statistically the only significant risk factor for conversion. CONCLUSION: We found several differences in frequency and clinical signs in these patients in contrast to previous data, probably due to different racial characteristics. The rate of progression is similar to previous reports despite of heterogeneity of these. Having IOP > 21 mm Hg was the only risk factor associated with progression in this sample. How to cite this article: Gomez Goyeneche HF, Hernandez-Mendieta DP, Rodriguez DA, Sepulveda AI, Toledo JD. Pigment Dispersion Syndrome Progression to Pigmentary Glaucoma in a Latin American Population. J Curr Glaucoma Pract 2015;9(3):69-72. PMID- 26997840 TI - Utility of Operative Glaucoma Tube Shunt Viscoelastic Bolus Flush. AB - OBJECTIVE: To assess the utility of viscoelastic injection to induce bleb expansion and decrease intraocular pressure (IOP) in eyes with encapsulated glaucoma tube shunt blebs. DESIGN: Case series. SUBJECTS AND PARTICIPANTS: Forty three glaucomatous eyes, including 13 eyes with congenital, 13 uveitic, 5 neovascular, 5 open angle, 4 narrow angle and 3 traumatic glaucomas. Methods, interventions or testing: All patients underwent viscoelastic flush procedure. A pre-bent 27 or 30-gauge cannula was passed through a 25-gauge paracentesis, advanced over the iris across the anterior chamber, and insinuated into the tube shunt lumen. Once the cannula was firmly lodged in position, 0.45 to 0.85 ml of viscoelastic was injected to hyperinflate the bleb. MAIN OUTCOME MEASURES: Paired t-tests were performed comparing preoperative IOP and number of medications used preoperatively vs levels measured at 1, 6, 12, 18 and 24 months. RESULTS: Intraocular pressure was reduced from a mean preoperative level of 26.0 +/- 1.2 (sem) mm Hg to 15.8 +/- 1.0 at 1 month, remaining stable thereafter at each 6 month interval with 15.1 +/- 1.1 mm Hg at 24 months (p < 0.0001). Medication use did not vary significantly from baseline. Pressure remained < 21 mm Hg after 2 years in 85% of eyes cannulated within 1 year of primary tube shunt implantation (n = 23), and in 62% of eyes cannulated more than 1 year after tube shunt placement (n = 20). CONCLUSION: Tube shunt expansion with bolus viscoelastic flush successfully restored encapsulated bleb function, providing a substantial (~10 mm Hg) IOP decrease into the mid-normal pressure range. This persisted in the majority of treated eyes for the entire study period. How to cite this article: Groth SL, Greider KL, Sponsel WE. Utility of Operative Glaucoma Tube Shunt Viscoelastic Bolus Flush. J Curr Glaucoma Pract 2015;9(3):73-76. PMID- 26997841 TI - CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma. AB - CYP1B1 is a dioxin-inducible enzyme belonging to the cytochrome P450 superfamily. It has been observed to be important in a variety of developmental processes including in utero development of ocular structures. Owing to its role in the developmental biology of eye, its dysfunction can lead to ocular developmental defects. This has been found to be true and CYP1B1 mutations have been observed in a majority of primary congenital glaucoma (PCG) patients from all over the globe. Primary congenital glaucoma is an irreversibly blinding childhood disorder (onset at birth or early infancy) typified by anomalous development of trabecular meshwork (TM). How CYP1B1 causes PCG is not known; however, some basic investigations have been reported. Understanding the CYP1B1 mediated etiopathomechanism of PCG is very important to identify targets for therapy and preventive management. In this perspective, we will make an effort to reconstruct the pathomechanism of PCG in the light of already reported information about the disease and the CYP1B1 gene. How to cite this article: Faiq MA, Dada R, Qadri R, Dada T. CYP1 B1-mediated Pathobiology of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):77-80. PMID- 26997842 TI - Diabetes Mellitus as a Risk Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature Review. AB - Glaucoma is a multifactorial condition under serious influence of many risk factors. The role of diabetes mellitus (DM) in glaucoma etiology or progression remains inconclusive. Although, the diabetic patients have different healing mechanism comparing to the general population and it has a possible-negative role on surgical outcomes. This review article attempts to analyze the association of both diseases, glaucoma and DM, before and after the surgery. The epidemiological studies, based mainly in population prevalence analyzes, have shown opposite outcomes in time and even in the most recent articles also the association remains inconclusive. On the contrary, the experimental models based on animal induced chronic hyperglycemia have shown an important association of both diseases, explained by common neurodegenerative mechanisms. Diabetic patients have a different wound healing process in the eye viz-a-viz other organs. The healing process is more and it results in lower surgical survival time, higher intraocular pressure (IOP) levels and, therefore, these patients usually need more medication to lower the IOP. Both randomized and nonrandomized retrospective and experimental molecular studies have shown the association between DM and glaucoma. Further studies are needed to get better explanations about outcomes on more recent surgical procedures and with the exponential use of antifibrotics. How to cite this article: Costa L, Cunha JP, Amado D, Pinto LA, Ferreira J. Diabetes Mellitus as a Risk Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature Review. J Curr Glaucoma Pract 2015;9(3):81-85. PMID- 26997845 TI - Elevated Intraocular Pressure after Descemet Stripping Automated Endothelial Keratoplasty in Patients with a Trabeculectomy: A Case Series. AB - We report a case series of three patients with previous trabeculectomies who developed elevated intraocular pressure (IOP) in the immediate postoperative period after routine Descemet stripping automated endothelial keratoplasty (DSAEK). All patients had functioning trabeculectomies preoperatively, and developed elevated IOP between 41 and 69 mm Hg within 24 hours following DSAEK surgery. The IOP was successfully controlled in all patients with topical IOP lowering medications and oral acetazolamide, with the addition of ocular massage and release of aqueous for two patients. Thereafter, all patients maintained well controlled IOPs. Patients with trabeculectomies should be followed-up closely immediately after DSAEK to monitor for raised IOP. The mechanism for this pressure rise is uncertain, but may involve air in the trabeculectomy sclerostomy or bleb resulting in blockage of aqueous flow. How to cite this article: Sheales MPH, Chan E, Ang GS, Kong YXG. Elevated Intraocular Pressure after Descemet Stripping Automated Endothelial Keratoplasty in Patients with a Trabeculectomy: A Case Series. J Curr Glaucoma Pract 2015;9(3):100-103. PMID- 26997846 TI - Editorial. PMID- 26997844 TI - Review on the Management of Primary Congenital Glaucoma. AB - Despite being documented in medical history from over 2400 years ago, primary congenital glaucoma (PCG), being a disease with low incidence rate, remains a challenge to ophthalmologists. The article provides a broad overview on the pathophysiology and diagnostic approach to PCG with major emphasis on the treatment options of PCG. While reviewing on the well-established treatment options, namely goniotomy, trabeculo-tomy and combined trabeculotomy trabeculectomy, emphasis has also been made to recent updates on secondary treatments: trabeculectomy, antimetabolites, glaucoma-drainage devices and cyclodestructive procedures. It is, however, important to note that the rarity of PCG places limitations on study design, most studies are, thus, retrospective, nonrandomized and have different definitions of surgical success. Ophthalmologists need to interpret the results with critical thinking and formulate individual treatment plans for each patient. How to cite this article: Yu Chan JY, Choy BNK, Alex LK Ng, Shum JWH. Review on the Management of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):92-99. PMID- 26997843 TI - The Results of the Use of Ahmed Valve in Refractory Glaucoma Surgery. AB - The treatment of refractory glaucoma (RG) is challenging. The commonly adopted strategy in RG treatment is a glaucoma drainage device (GDD) implantation, which despite its radical nature may not always provide the desired intraocular pressure (IOP) levels for a long term. This review is based on the scientific literature on Ahmed glaucoma valve (AGV) implantation for refractory glaucoma. The technique of AGV implantation is described and data for both the types, FP7 and FP8 performance are presented. The outcome with adjunct antimetabolite and anti-VEGF drugs are also highlighted. An insight is given about experimental and histological examinations of the filtering bleb encapsulation. The article also describes various complications and measures to prevent them. How to cite this article: Bikbov MM, Khusnitdinov II. The Results of the Use of Ahmed Valve in Refractory Glaucoma Surgery. J Curr Glaucoma Pract 2015;9(3):86-91. PMID- 26997848 TI - BAYESIAN SPATIAL-TEMPORAL MODELING OF ECOLOGICAL ZERO-INFLATED COUNT DATA. AB - A Bayesian hierarchical model is developed for count data with spatial and temporal correlations as well as excessive zeros, uneven sampling intensities, and inference on missing spots. Our contribution is to develop a model on zero inflated count data that provides flexibility in modeling spatial patterns in a dynamic manner and also improves the computational efficiency via dimension reduction. The proposed methodology is of particular importance for studying species presence and abundance in the field of ecological sciences. The proposed model is employed in the analysis of the survey data by the Northeast Fisheries Sciences Center (NEFSC) for estimation and prediction of the Atlantic cod in the Gulf of Maine - Georges Bank region. Model comparisons based on the deviance information criterion and the log predictive score show the improvement by the proposed spatial-temporal model. PMID- 26997847 TI - Bacteriological Profile and Antimicrobial Susceptibility Pattern of Blood Culture Isolates among Septicemia Suspected Children in Selected Hospitals Addis Ababa, Ethiopia. AB - BACKGROUND: Blood stream infections are major cause of morbidity and mortality in children in developing countries. The emerging of causative agents and resistance to various antimicrobial agents are increased from time to time. The main aim of this study was to determine the bacterial agents and antimicrobial susceptibility patterns among children suspected of having septicemia. METHODS: A cross sectional study involved about 201 pediatric patients (<= 12 years) was conducted from October 2011 to February 2012 at pediatric units of TikurAnbessa Specialized Hospital and Yekatit 12 Hospital. Standard procedure was followed for blood sample collection, isolate identifications and antimicrobial susceptibility testing. RESULTS: Among 201 study subjects 110 (54.7%) were males. Majority 147 (73.1%) of them were neonates (<= 28 days). The mean length of hospital stay before sampling was 4.29 days. Out of the 201 tested blood samples, blood cultures were positive in 56 (27.9%).Gram negative and Gram positive bacteria constituted 29(51.8%) and 26(46.4%), respectively. The most frequent pathogen found was Staphylococcus aureus 13 (23.2%), followed by Serratia marcescens 12(21.4%), CoNS 11(19.6%), klebsiella spp 9(16%) and Salmonella spp 3(5.4%). Majority of bacterial isolates showed high resistance to Ampicillin, Penicillin, Co-trimoxazole, Gentamicin and Tetracycline which commonly used in the study area. CONCLUSION: Majority of the isolates were multidrug resistant. These higher percentages of multi-drug resistant emerged isolates urge us to take infection prevention measures and to conduct other large studies for appropriate empiric antibiotic choice. PMID- 26997849 TI - Differences Between People Who Use Only Facebook And Those Who Use Facebook Plus Twitter. AB - Facebook (FB) and Twitter are popular social networking sites. This study examined differences between those who use both sites versus only FB, to test the hypothesis that mono-users differ in their personality characteristics from users active in both websites. Participants were 205 undergraduate students; 96 only used FB, 109 used FB and Twitter. Participants who used both sites reported significantly lower loneliness, higher number of FB friends, and lower number of minutes spent online, as compared to those who only used FB. Loneliness was positively associated with FB use only in those who used FB alone, but was negatively associated with and negatively predicted both FB and Twitter use in those who used both websites. Findings suggest that more intense use of online interactions is more frequently found in mono-users (people using only Facebook) as compared to those using both websites, and it is predicted by increased feelings of loneliness. The current study findings provide additional insights on what personality factors may make some people prone to excessive use of social networking sites. PMID- 26997850 TI - Do Adults Show an Effect of Delayed First Language Acquisition When Calculating Scalar Implicatures? AB - Language acquisition involves learning not only grammatical rules and a lexicon, but also what someone is intending to convey with their utterance: the semantic/pragmatic component of language. In this paper we separate the contributions of linguistic development and cognitive maturity to the acquisition of the semantic/pragmatic component of language by comparing deaf adults who had either early or late first exposure to their first language (ASL). We focus on the particular type of meaning at the semantic/pragmatic interface called scalar implicature, for which preschool-age children typically differ from adults. Children's behavior has been attributed to either their not knowing appropriate linguistic alternatives to consider or to cognitive developmental differences between children and adults. Unlike children, deaf adults with late language exposure are cognitively mature, although they never fully acquire some complex linguistic structures, and thus serve as a test for the role of language in such interpretations. Our results indicate an overall high performance by late learners, especially when implicatures are not based on conventionalized items. However, compared to early language learners, late language learners compute fewer implicatures when conventionalized linguistic alternatives are involved (e.g. ). We conclude that (i) in general, Gricean pragmatic reasoning does not seem to be impacted by delayed first language acquisition and can account for multiple quantity implicatures, but (ii) the creation of a scale based on lexical items can lead to ease in alternative creation that may be advantageously learned early in life, and that this may be one of several factors contributing to differences between adults and children on scalar implicature tasks. PMID- 26997851 TI - Polysubstance Use among Minority Adolescent Males Incarcerated for Serious Offenses. AB - BACKGROUND: Adolescent juvenile offenders are at high risk for problems associated with drug use, including polysubstance use (i.e., use of a variety of drugs). The combination of juvenile offending and polysubstance use presents a significant public and child health concern. OBJECTIVE: This study explored polysubstance use among a sample of youth incarcerated for serious offenses. We examined several risk factors for substance use and delinquency (i.e., early and frequent substance use, prior history of arrests, school expulsion, Black ethnicity), as well as the association between aggression and polysubstance use. METHODS: Data were collected via questionnaires from 373 serious male juvenile offenders upon intake into a secure locked facility. Youth were on average 16 years old, and minority youth were overrepresented (28.1% Black, 53.1% Latino). Poisson regressions were used to assess the associations between the risk factors, aggression, and polysubstance use. RESULTS: Consistent with the literature, Black youth reported less polysubstance use and later age of drug use onset than White and Latino youth. Findings suggest that Latino juvenile offenders and those with an early and problematic pattern of substance use are at heightened risk for polysubstance use. Aggression was not significantly related to polysubstance use, over and above the risk factors. CONCLUSIONS: Given that Latino youth experience low rates of treatment for substance use, the development of culturally-sensitive interventions for these youth is needed. Interventions should also be multifaceted to address the multitude of risk factors associated with polysubstance use among juvenile offenders. PMID- 26997853 TI - ITC and NMR Analysis of the Encapsulation of Fatty Acids within a Water-Soluble Cavitand and its Dimeric Capsule. AB - We report here NMR and ITC studies of the binding of ionizable guests (carboxylate acids) to a deep-cavity cavitand. These studies reveal that the shortest guests favored 1:1 complex formation, but the longer the alkyl chain the more the 2:1 host-guest capsule is favored. For intermediate-sized guests, the equilibrium between these two states is controlled by pH; at low values the capsule containing the carboxylic acid guest is favored, whereas as the pH is raised deprotonation of the guest favors the 1:1 complex. Interestingly, for one host-guest pair the energy required to de-cap the 2:1 capsular complex and form the 1:1 complex is sufficient to shift the pKa of the guest by ~ 3-4 orders of magnitude (4.1-5.4 kcal mol-1). The two largest guests examined form stable 2:1 capsules, with in both cases the guest adopting a relatively high energy J-shaped motif. Furthermore, these 2:1 complexes are sufficiently stable that at high pH guest deprotonation occurs without de-capping of the capsule. PMID- 26997852 TI - The Longitudinal Effects of Chronic Mediated Exposure to Political Violence on Ideological Beliefs About Political Conflicts Among Youths. AB - This study examines the effects of chronic (i.e., repeated and cumulative) mediated exposure to political violence on ideological beliefs regarding political conflict. It centers on these effects on young viewers, from preadolescents to adolescents. Ideological beliefs refers here to support of war, perception of threat to one's nation, and normative beliefs concerning aggression toward the out-group. A longitudinal study was conducted on a sample of Israeli and Palestinian youths who experience the Israeli-Palestinian conflict firsthand (N = 1,207). Two alternative hypotheses were tested: that chronic exposure via the media increases support for war and aggression and elevates feeling of threat, or that chronic exposure via the media strengthens preexisting beliefs. Results demonstrated that higher levels of exposure were longitudinally related to stronger support for war. Regarding normative beliefs about aggression and threat to one's nation, mediated exposure reinforced initial beliefs, rendering the youths more extreme in their attitudes. These results mostly support the conceptualization of the relation between media violence and behaviors as "reciprocally determined" or "reinforcing spirals." The results are also discussed in light of the differences found between the effect of exposure to political violence firsthand and exposure via the media. PMID- 26997854 TI - Seesaw Discipline: The Interactive Effect of Harsh and Lax Discipline on Youth Psychological Adjustment. AB - Although extant research documents the negative consequences of harsh and lax discipline for youth, little empirical attention has been devoted to understanding the impact when parents utilize both strategies. As such, the current study was designed to explore the interaction of harsh and lax discipline on youth internalizing and externalizing symptoms in three developmental periods (early childhood, middle childhood, and adolescence). Participants were 615 parents (55 % female) and one of their 3-to-17 year old children (45 % female). Parents provided reports of their harsh and lax parenting tactics as well as offspring internalizing and externalizing symptoms. Multiple linear regression analyses were utilized to examine the relations between the interaction of harsh and lax parenting on youth symptoms. The interaction between harsh and lax discipline was significantly related to youth internalizing, but not externalizing, problems in the both the young and middle childhood samples and marginally significant in the adolescence sample: Seesaw discipline - a novel construct indicative of high levels of both harsh and lax discipline - was associated with the highest levels of youth internalizing problems. Parents who engage in seesaw parenting have children and adolescents who are more likely to evidence internalizing symptoms. Such findings may inform prevention and intervention efforts that target dysfunctional discipline. PMID- 26997855 TI - Perspectives on Engagement Barriers and Alternative Delivery Formats from Non Completers of Community-Run Parenting Programs. PMID- 26997856 TI - Does Self-compassion Protect Adolescents from Stress? PMID- 26997857 TI - A Longitudinal Study of Truant Youths' Involvement in Sexual Risk Behavior. PMID- 26997858 TI - Development of a model to determine oxygen consumption when crawling. AB - During a mine disaster or emergency, underground air can quickly become contaminated. In these circumstances, all underground mine workers are taught to don breathable air supply units at the first sign of an emergency. However, no contemporary oxygen consumption data is available for the purposes of designing breathing air supply equipment specifically for mine escape. Further, it would be useful to quantify the oxygen requirements of breathing air supply users for various escape scenarios. To address this need, 14 participants crawled a distance of 305 m each while their breath-by-breath oxygen consumption measurements were taken. Using these data, linear regression models were developed to determine peak and average oxygen consumption rates as well as total oxygen consumption. These models can be used by manufacturers of breathing air supply equipment to aid in the design of devices that would be capable of producing sufficient on-demand oxygen to allow miners to perform self-escape. PMID- 26997859 TI - Acceptance and Commitment Therapy with Older Adults: Rationale and Considerations. AB - Older adults are the fastest growing segment of the population. With these changing demographics, mental health professionals will be seeing more older clients. Additionally, older adults are an underserved population in that most older adults in need of mental health services do not receive treatment. Thus, it is essential that treatments for mental and behavioral health problems are empirically supported with older adults and that mental health professionals are aware of the special needs of older adult populations. Acceptance and Commitment Therapy (ACT) is an emerging approach to the treatment of distress. The purpose of this article is to provide a rationale for using ACT with older adults based on gerontological theory and research. We also review research on ACT-related processes in later life. We present a case example of an older man with depression and anxiety whom we treated with ACT. Finally, we describe treatment recommendations and important adaptations that need to be considered when using ACT with older adults and discuss important areas for future research. PMID- 26997860 TI - Tuning of shortening speed in coleoid cephalopod muscle: no evidence for tissue specific muscle myosin heavy chain isoforms. AB - The contractile protein myosin II is ubiquitous in muscle. It is widely accepted that animals express tissue-specific myosin isoforms that differ in amino acid sequence and ATPase activity in order to tune muscle contractile velocities. Recent studies, however, suggested that the squid Doryteuthis pealeii might be an exception; members of this species do not express muscle-specific myosin isoforms, but instead alter sarcomeric ultrastructure to adjust contractile velocities. We investigated whether this alternative mechanism of tuning muscle contractile velocity is found in other coleoid cephalopods. We analyzed myosin heavy chain transcript sequences and expression profiles from muscular tissues of a cuttlefish, Sepia officinalis, and an octopus, Octopus bimaculoides, in order to determine if these cephalopods express tissue-specific myosin heavy chain isoforms. We identified transcripts of four and six different myosin heavy chain isoforms in S. officinalis and O. bimaculoides muscular tissues, respectively. Transcripts of all isoforms were expressed in all muscular tissues studied, and thus S. officinalis and O. bimaculoides do not appear to express tissue-specific muscle myosin isoforms. We also examined the sarcomeric ultrastructure in the transverse muscle fibers of the arms of O. bimaculoides and the arms and tentacles of S. officinalis using transmission electron microscopy and found that the fast contracting fibers of the prey capture tentacles of S. officinalis have shorter thick filaments than those found in the slower transverse muscle fibers of the arms of both species. It thus appears that coleoid cephalopods, including the cuttlefish and octopus, may use ultrastructural modifications rather than tissue-specific myosin isoforms to adjust contractile velocities. PMID- 26997861 TI - The Relation of Knowledge-Text Integration Processes and Reading Comprehension in 7th- to 12th-Grade Students. AB - The integration of knowledge during reading was tested in 1,109 secondary school students. Reading times for the second sentence in a pair (Jane's headache went away) were compared in conditions where the first sentence was either causally or temporally related to the first sentence (Jane took an aspirin vs. Jane looked for an aspirin). Mixed-effects explanatory item response models revealed that at higher comprehension levels, sentences were read more quickly in the causal condition. There were no condition-related reading time differences at lower comprehension levels. This interaction held with comprehension- and inference related factors (working memory, word and world knowledge, and word reading efficiency) in the models. Less skilled comprehenders have difficulty in knowledge-text integration processes that facilitate sentence processing during reading. PMID- 26997862 TI - Towards a Theory of Variation in the Organization of the Word Reading System. AB - The strategy underlying most computational models of word reading is to specify the organization of the reading system-its architecture and the processes and representations it employs-and to demonstrate that this organization would give rise to the behavior observed in word reading tasks. This approach fails to adequately address the variation in reading behavior observed across and within linguistic communities. Only computational models that incorporate learning can fully account for variation in organization. However, even extant learning models (e.g., the triangle model) must be extended if they are to fully account for variation in organization. The challenges associated with extending theories in this way are discussed. PMID- 26997863 TI - Promoting a Sustainable Academic-Correctional Health Partnership: Lessons for Systemic Action Research. AB - In the United States, the phenomenon of mass incarceration has created a public health crisis. One strategy for addressing this crisis involves developing a correctional agency - academic institution partnership tasked with augmenting the quality and quantity of evidence-based healthcare delivered in state prisons and attracting a greater number of health professionals to the field of correctional health research. Using a Connecticut correctional agency - academic institution partnership as a case example, the present paper examines some of the key challenges encountered over the course of a 3-year capacity-building initiative. Particular attention is given to agency and institution characteristics both at the structural level and in terms of divergent stakeholder perspectives. The authors find that future partnership development work in this area will likely benefit from close attention to predictable sources of temporal variation in agency capability to advance project-related aims. PMID- 26997864 TI - Assessing Combinational Drug Efficacy in Cancer Cells by Using Image-based Dynamic Response Analysis. AB - The landscape of translational research has been shifting toward drug combination therapies. Pairing of drugs allows for more types of drug interaction with cells. In order to accurately and comprehensively assess combinational drug efficacy, analytical methods capable of recognizing these alternative reactions will be required to prioritize those drug candidates having better chances of delivering appreciable therapeutic benefits. Traditional efficacy measures are primarily based on the "extent" of drug inhibition, which is the percentage of cells being killed after drug exposure. Here, we introduce a second dimension of evaluation criterion, speed of killing, based on a live cell imaging assay. This dynamic response trajectory approach takes advantage of both "extent" and "speed" information and uncovers synergisms that would otherwise be missed, while also generating hypotheses regarding important mechanistic modes of drug action. PMID- 26997866 TI - Development and Validation of Stability-Indicating RP-HPLC Method for Simultaneous Determination of Metformin HCl and Glimepiride in Fixed-Dose Combination. AB - A simple reversed-phase high-performance liquid chromatography method was developed and validated for simultaneous determination of Metformin hydrochloride (MET) and Glimepiride (GLM) in combination and estimation of their principal degradation products. The separation was achieved using JASCO Finepak SIL (250 mm * 4.6 mm i.d. 5 MUm) at ambient temperature. The optimized mobile phase composed of an aqueous phase (20 mM phosphate buffer, adjusted to pH 3.0) and an organic phase (methanol:acetonitrile; 62.5:37.5) in the ratio of 80:20. The flow rate was 1 mL/minute, and the analytes were detected at 230 nm. The developed method was validated for accuracy, precision, specificity, linearity, and sensitivity. The chromatographic analysis time was approximately six minutes with the complete resolution of MET (Rt = 2.75 minutes) and GLM (Rt = 5.87 minutes). The method exhibited good linearity over the range of 5-30 MUg/mL for MET and 1-10 MUg/mL for GLM. The drugs in combination were subjected to various stress degradation studies as per the International Conference Harmonization (ICH) guidelines. Results obtained from the stress degradation studies revealed that the developed method is applicable for stability studies. PMID- 26997865 TI - Urine Proteome Biomarkers in Kidney Diseases. I. Limits, Perspectives, and First Focus on Normal Urine. AB - Urine proteome is a potential source of information in renal diseases, and it is considered a natural area of investigation for biomarkers. Technology developments have markedly increased the power analysis on urinary proteins, and it is time to confront methodologies and results of major studies on the topics. This is a first part of a series of reviews that will focus on the urine proteome as a site for detecting biomarkers of renal diseases; the theme of the first review concerns methodological aspects applied to normal urine. Main issues are techniques for urine pretreatment, separation of exosomes, use of combinatorial peptide ligand libraries, mass spectrometry approaches, and analysis of data sets. Available studies show important differences, suggesting a major confounding effect of the technologies utilized for analysis. The objective is to obtain consensus about which approaches should be utilized for studying urine proteome in renal diseases. PMID- 26997867 TI - Modeling Intercellular Communication as a Survival Strategy of Cancer Cells: An In Silico Approach on a Flexible Bioinformatics Framework. AB - Intercellular communication is very important for cell development and allows a group of cells to survive as a population. Cancer cells have a similar behavior, presenting the same mechanisms and characteristics of tissue formation. In this article, we model and simulate the formation of different communication channels that allow an interaction between two cells. This is a first step in order to simulate in the future processes that occur in healthy tissue when normal cells surround a cancer cell and to interrupt the communication, thus preventing the spread of malignancy into these cells. The purpose of this study is to propose key molecules, which can be targeted to allow us to break the communication between cancer cells and surrounding normal cells. The simulation is carried out using a flexible bioinformatics platform that we developed, which is itself based on the metaphor chemistry-based model. PMID- 26997869 TI - Integrating Estimates of the Social and Individual Costs of Caregiving into Dementia Treatment Trials. AB - A variety of new treatments for dementia are awaiting or undergoing randomized clinical trails. These trials focus on outcomes such as changes in cognitive function, physical function, or amyloid plaques. What is quite important and is too often missing from these trials are estimates of the impact of these treatments on the social and individual costs of providing care for those facing dementia. Until outcomes such as family caregiver time and caregiver burden are included in trails of dementia treatments, the picture of how well these treatments work will be distressingly incomplete. PMID- 26997868 TI - Autophagy and Apoptotic Crosstalk: Mechanism of Therapeutic Resistance in HER2 Positive Breast Cancer. AB - While breast cancer patients benefit from the use of HER2 inhibitors, many fail therapy and become resistant to treatment, indicating a critical need to prevent treatment failure. A number of studies have emerged that highlight the catabolic process of autophagy in breast cancer as a mechanism of resistance to chemotherapy and targeted inhibitors. Furthermore, recent research has begun to dissect how autophagy signaling crosstalks with apoptotic signaling. Thus, a possible strategy in fighting resistance is to couple targeting of apoptotic and autophagy signaling pathways. In this review, we discuss how cellular response by autophagy circumvents cell death to promote resistance of breast cancers to HER2 inhibitors, as well as the potential avenues of therapeutic intervention. PMID- 26997870 TI - Anti-Infective Metabolites of a Newly Isolated Bacillus thuringiensis KL1 Associated with Kalmegh (Andrographis paniculata Nees.), a Traditional Medicinal Herb. AB - This study was conducted to isolate endophytic bacteria possessing anti-infective property from Kalmegh (Andrographis paniculata Nees.), a well-known medicinal plant. A total of 23 strains were isolated from this plant among which the strain KL1, isolated from surface-sterilized leaf of this medicinal herb, showed broad spectrum antagonism against an array of Gram-positive and -negative bacterial pathogens. Ethyl acetate extract of KL1-fermented media yielded a greenish amorphous substance retaining anti-infective property. Solvent-extracted crude material was separated by thin-layer chromatography, and the active ingredient was located by autobiogram analysis. The purified anti-infective compound was found as anthracene derivative as analyzed by ultraviolet and Fourier transform infrared spectroscopy. The strain was identified as Bacillus thuringiensis KL1 from cultural, physiochemical, and molecular aspects. The above results indicate the pharmaceutical potential of the candidate isolate. PMID- 26997871 TI - A Review of Impact of Tobacco Use on Patients with Co-occurring Psychiatric Disorders. AB - Consumption of tobacco has been a worldwide problem over the past few decades due to the highly prevalent tobacco-attributable complications. Tobacco use has also been found to be more prevalent in patients with psychiatric disorders. Therefore, we conducted this review about the impact of tobacco use on co occurring psychiatric disorders. Various facets of this interaction between tobacco use among those with co-occurring psychiatric disorders have been explored. It has been found that people with psychiatric disorders have a higher chance of currently smoking tobacco and lesser chance of cessation. Tobacco use and mental disorders continue to share a complex relationship that has been further evolving after the change in the pattern of tobacco use and also the advent of newer modalities of treatment. However, at the same time, it is believed that cessation of smoking may lead to improvement in the symptoms of mental illness. PMID- 26997875 TI - Impact of the Residual SYNTAX Score on Outcomes of Revascularization in Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Disease. AB - Primary percutaneous coronary intervention (P-PCI) has become the preferred reperfusion strategy in ST-elevation myocardial infarction (STEMI) when performed by an experienced team in a timely manner. However, no consensus exists regarding the management of multivessel coronary disease detected at the time of P-PCI. AIM: The aim of this study was to evaluate the use of the residual SYNTAX score (rSS) following a complete vs. culprit-only revascularization strategy in patients with STEMI and multivessel disease (MVD) to quantify the extent and complexity of residual coronary stenoses and their impact on adverse ischemic outcomes. METHODS: Between October 1, 2012, and November 30, 2013, we enrolled 120 consecutive STEMI patients with angiographic patterns of multivessel coronary artery disease (CAD) who had a clinical indication to undergo PCI. The patients were subdivided into those who underwent culprit-only PCI (60 patients) and those who underwent staged-multivessel PCI during the index admission or who were staged within 30 days of the index admission (60 patients). Both the groups were well matched with regard to clinical statuses and lesion characteristics. Clinical outcomes at one year were collected, and the baseline SYNTAX score and rSS were calculated. RESULTS: The mean total stent length (31.07 +/- 12.7 mm vs. 76.3 +/- 14.1 mm) and the number of stents implanted per patient (1.34 +/- 0.6 vs. 2.47 +/- 0.72) were higher in the staged-PCI group. The rSS was higher in the culprit-only PCI group (9.7 +/- 5.7 vs. 1.3 +/- 1.99). The angiographic and clinical results after a mean follow-up of 343 +/- 75 days demonstrated no significant difference in the occurrence of in-hospital Major Adverse Cardiac and Cerebrovascular Events (MACCE) between both the groups (6.7% vs. 5%, P = 1.000). However, patients treated with staged PCI with an rSS <=8 had significant reductions in one-year MACCE (10.7% vs. 30.5%, P = 0.020*), death/Myocardial infarction (MI)/Cerebrovascular accident (CVA) (5% vs. 13.8%, P = 0.016*), and repeat revascularization (4.8% vs. 25%, P = 0.001*). We found that culprit-only, higher GRACE risk scores at discharge and an rSS >8 were independent predictors of MACCE at one year. CONCLUSIONS: Staged PCI that achieves reasonable complete revascularization (rSS <=8) improves mid-term survival and reduces the incidence of repeat PCI in patients with STEMI and MVD. Nonetheless, large-scale randomized trials are required to establish the optimal revascularization strategy for these high-risk patients. PMID- 26997873 TI - Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel. AB - Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-beta are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response. PMID- 26997874 TI - Role of Biomarkers in the Development of PARP Inhibitors. AB - Defects in DNA repair lead to genomic instability and play a critical role in cancer development. Understanding the process by which DNA damage repair is altered or bypassed in cancer may identify novel therapeutic targets and lead to improved patient outcomes. Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) has an important role in DNA repair, and novel therapeutics targeting PARP1 have been developed to treat cancers with defective DNA repair pathways. Despite treatment successes with PARP inhibitors (PARPi), intrinsic and acquired resistances have been observed. Preclinical studies and clinical trials in cancer suggest that combination therapy using PARPi and platinating agents is more effective than monotherapy in circumventing drug resistance mechanisms. Additionally, identification of biomarkers in response to PARPi will lead to improved patient selection for targeted cancer treatment. Recent technological advances have provided the necessary tools to examine many potential avenues to develop such biomarkers. This review examines the mechanistic rationale of PARP inhibition and potential biomarkers in their development for personalized therapy. PMID- 26997876 TI - CETP Inhibition: Past Failures and Future Hopes. AB - The atheroprotective role of high-density lipoprotein cholesterol (HDL-C) in cardiovascular disease has been unequivocally established, and epidemiological data have clearly demonstrated a strong inverse relationship between HDL-C levels and the risk of cardiovascular events, which is independent of the low-density lipoprotein cholesterol (LDL-C) levels. Thus, it would be logical to hypothesize that raising HDL-C might potentially lead to a reduction of cardiovascular risk. Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from HDL to very low-density lipoprotein and LDL. Therefore, CETP inhibition raises HDL-C levels and decreases LDL-C levels. The first trials with CETP inhibitors failed to show a reduction in cardiovascular events. However, newer CETP inhibitors with more favorable effects on lipids are presently being tested in clinical trials with the hope that their use may lead to a reduction in cardiovascular risk. This review aims to provide the current evidence regarding CETP inhibition, as well as the clinical and scientific data pertaining to the new CETP inhibitors in development. PMID- 26997877 TI - A CD2AP Mutation Associated with Focal Segmental Glomerulosclerosis in Young Adulthood. AB - Mutations in CD2-associated protein (CD2AP) have been identified in patients with focal segmental glomerulosclerosis (FSGS); however, reports of CD2AP mutations remain scarce. We performed Sanger sequencing in a patient with steroid-resistant FSGS and identified a heterozygous CD2AP mutation (p.T374A, c.1120 A > G). Our patient displayed mild cognitive decline, a phenotypic characteristic not previously associated with CD2AP-associated FSGS. His proteinuria was remarkably reduced by treatment with cyclosporine A. Our findings expand the genetic spectrum of CD2AP-associated disorders and broaden the associated phenotype with the co-occurrence of cognitive decline. Our case shows that cyclosporin A is a treatment option for CD2AP-associated nephropathy. PMID- 26997872 TI - Novel Molecular Markers for Breast Cancer. AB - The use of molecular biomarkers assures that breast cancer (BC) patients receive optimal treatment. Established biomarkers, such as estrogen receptor, progesterone receptor, HER2, and Ki67, have been playing significant roles in the subcategorization of BC to predict the prognosis and decide the specific therapy to each patient. Antihormonal therapy using 4-hydroxytamoxifen or aromatase inhibitors have been employed in patients whose tumor cells express hormone receptors, while monoclonal antibody to HER2 has been administered to HER2 positive BCs. Although new therapeutic agents have been developed in the past few decades, many patients still die of the disease due to relapse; thus, novel molecular markers that predict therapeutic failure and those that can be targets for specific therapy are expected. We have chosen four of such molecules by reviewing recent publications, which are cyclin E, B-Myb, Twist, and DMP1beta. The oncogenicity of these molecules has been demonstrated in vivo and/or in vitro through studies using transgenic mice or siRNAs, and their expressions have been shown to be associated with shortened overall or disease-free survival of BC patients. The former three molecules have been shown to accelerate epithelial mesenchymal transition that is often associated with cancer stem cell-ness and metastasis; all these four can be novel therapeutic targets as well. Thus, large prospective studies employing immunohistochemistry will be needed to establish the predictive values of these molecules in patients with BC. PMID- 26997878 TI - Tubulointerstitial Nephritis and Uveitis Syndrome: Are Drugs Offenders or Bystanders? AB - A 16-year-old female patient was admitted to our hospital due to progressive renal dysfunction with an increased serum creatinine (sCr) level of 1.7 mg/dL. Her clinical course without any ocular manifestations and results of drug induced, lymphocyte-stimulating tests, in addition to a renal histological assessment, initially encouraged us to ascribe the patient's renal abnormalities to drug-induced acute interstitial nephritis (AIN). Four months later, she started to complain about reduced visual acuity when she was found to have anterior bilateral uveitis despite the recovered renal function with almost constant sCr levels around 0.7 mg/dL. Thus, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was finally made. Our case illustrates the difficulties in distinguishing late-onset uveitis TINU syndrome from drug-induced AIN at the time of the renal biopsy, thereby suggesting the importance of a longitudinal follow-up to overcome the potential underdiagnosis of the disease. Several diagnostic conundrums that emerged in this case are also discussed. PMID- 26997879 TI - Genetic Susceptibility to Interstitial Lung Disease Associated with Systemic Sclerosis. AB - Systemic sclerosis (SSc) is a connective tissue disease that is characterized by tissue fibrosis, microvasculopathy, and autoimmunity. Interstitial lung disease (ILD) is a common complication of SSc and is one of the frequent causes of mortality in SSc. Although the exact etiology of SSc remains unknown, clinical and experimental investigations have suggested that genetic and environmental factors are relevant to the pathogenesis of SSc and SSc-ILD. More than 30 genes have been identified as susceptibility loci for SSc, most of which are involved in immune regulation and inflammation. It is thought that the key pathogenesis of SSc-ILD is caused by the release of profibrotic mediators such as transforming growth factor beta1 and connective tissue growth factor from lung cells induced by a persistent damage. This review presents the genetic susceptibility to SSc ILD, including human leukocyte antigen and non-human leukocyte antigen genes, especially focusing on connective tissue growth factor. PMID- 26997880 TI - Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia. AB - Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID- 26997881 TI - Effect of Infant Formula Containing a Low Dose of the Probiotic Bifidobacterium lactis CNCM I-3446 on Immune and Gut Functions in C-Section Delivered Babies: A Pilot Study. AB - BACKGROUND: In the absence of breast-feeding and its immunomodulatory factors, supplementation of starter infant formula (IF) with probiotics is currently used to support immune functions and gut development. AIM: To assess whether immune related beneficial effects of regular dose (10(7) CFU/g of powder) of the probiotic Bifidobacterium lactis CNCM I-3446 (hereafter named B. lactis) in starter IF supplementation can be maintained with starter IF containing a low dose (10(4) CFU/g of powder) of B. lactis. METHOD: This trial was designed as a pilot, prospective, double-blind, randomized, single-center clinical trial of two parallel groups (n = 77 infants/group) of C-section delivered infants receiving a starter IF containing either low dose or regular dose of the probiotic B. lactis from birth to six months of age. In addition, a reference group of infants breast fed for a minimum of four months (n = 44 infants), also born by C-section, were included. All groups were then provided follow-up formula without B. lactis up to 12 months of age. Occurrence of diarrhea, immune and gut maturation, responses to vaccinations, and growth were assessed from birth to 12 months. The effect of low dose B. lactis formula was compared to regular-dose B. lactis formula, considered as reference for IF with probiotics, and both were further compared to breast feeding as a physiological reference. RESULTS: Data showed that feeding low-dose B. lactis IF provides similar effects as feeding regular-dose B. lactis IF or breast milk. No consistent statistical differences regarding early life protection against gastrointestinal infections, immune and gut maturation, microbiota establishment, and growth were observed between randomized formula-fed groups as well as with the breast-fed reference group. CONCLUSION: This pilot study suggests that supplementing C-section born neonates with low-dose B. lactis containing starter formula may impact immune as well as gut maturation similarly to regular-dose B. lactis, close to the breast-feeding reference. PMID- 26997882 TI - Larval morphology and phylogenetic position of Drusus balcanicus, Drusus botosaneanui, Drusus serbicus and Drusus tenellus (Trichoptera: Limnephilidae: Drusinae). AB - In a recent 3-gene phylogeny of the Trichoptera subfamily Drusinae Banks, 1916 molecular data clearly correlated with the morphology and feeding ecology of larvae. The largest of three main groups, the Drusinae grazer clade, exhibits an unusual larval feeding ecology for Limnephilidae, and is the most diverse group. In this paper we describe four previously unknown Drusinae larvae from this clade: Drusus balcanicus Kumanski, 1973 (micro-endemic to Eastern Balkans); Drusus botosaneanui Kumanski, 1968 (Dinaric Western Balkans, Hellenic and Eastern Balkan, Asia Minor), Drusus serbicus Marinkovic-Gospodnetic, 1971a (micro-endemic to Dinaric Western Balkans); and Drusus tenellus (Klapalek, 1898) (Carpathians, Dinaric Eastern Balkans). Characteristically, the larvae of these species develop toothless mandibles typical for the Drusinae grazer clade. Larvae and adults were unambiguously associated by a phylogenetic approach based on two mitochondrial (mtCOI, mtLSU= 16S rDNA) and two nuclear genes (nuWG, nuCAD). In addition, information on the morphology of the larvae is given and the diagnostic features necessary for identification are illustrated. PMID- 26997883 TI - Spinel-rock salt transformation in LiCoMnO4-delta. AB - The transformation on heating LiCoMnO4, with a spinel structure, to LiCoMnO3, with a cation-disordered rock salt structure, accompanied by loss of 25% of the oxygen, has been followed using a combination of diffraction, microscopy and spectroscopy techniques. The transformation does not proceed by a topotactic mechanism, even though the spinel and rock salt phases have a similar, cubic close-packed oxygen sublattice. Instead, the transformation passes through two stages involving, first, precipitation of Li2MnO3, leaving behind a Li-deficient, Co-rich non-stoichiometric spinel and, second, rehomogenization of the two-phase assemblage, accompanied by additional oxygen loss, to give the homogeneous rock salt final product; a combination of electron energy loss spectroscopy and X-ray absorption near edge structure analyses showed oxidation states of Co2+ and Mn3+ in LiCoMnO3. Subsolidus phase diagram determination of the Li2O-CoO x -MnO y system has established the compositional extent of spinel solid solutions at approximately 500 degrees C. PMID- 26997884 TI - Designing of self-deploying origami structures using geometrically misaligned crease patterns. AB - Usually, origami-based morphing structures are designed on the premise of 'rigid folding', i.e. the facets and fold lines of origami can be replaced with rigid panels and ideal hinges, respectively. From a structural mechanics viewpoint, some rigid-foldable origami models are overconstrained and have negative degrees of freedom (d.f.). In these cases, the singularity in crease patterns guarantees their rigid foldability. This study presents a new method for designing self deploying origami using the geometrically misaligned creases. In this method, some facets are replaced by 'holes' such that the systems become a 1-d.f. mechanism. These perforated origami models can be folded and unfolded similar to rigid-foldable (without misalignment) models because of their d.f. focusing on the removed facets, the holes will deform according to the motion of the frame of the remaining parts. In the proposed method, these holes are filled with elastic parts and store elastic energy for self-deployment. First, a new extended rigid folding simulation technique is proposed to estimate the deformation of the holes. Next, the proposed method is applied on arbitrary-size quadrilateral mesh origami. Finally, by using the finite-element method, the authors conduct numerical simulations and confirm the deployment capabilities of the models. PMID- 26997885 TI - Geometric methods for optimal sensor design. AB - The Kalman-Bucy filter is the optimal estimator of the state of a linear dynamical system from sensor measurements. Because its performance is limited by the sensors to which it is paired, it is natural to seek optimal sensors. The resulting optimization problem is however non-convex. Therefore, many ad hoc methods have been used over the years to design sensors in fields ranging from engineering to biology to economics. We show in this paper how to obtain optimal sensors for the Kalman filter. Precisely, we provide a structural equation that characterizes optimal sensors. We furthermore provide a gradient algorithm and prove its convergence to the optimal sensor. This optimal sensor yields the lowest possible estimation error for measurements with a fixed signal-to-noise ratio. The results of the paper are proved by reducing the optimal sensor problem to an optimization problem on a Grassmannian manifold and proving that the function to be minimized is a Morse function with a unique minimum. The results presented here also apply to the dual problem of optimal actuator design. PMID- 26997886 TI - Dynamics of non-stationary processes that follow the maximum of the Renyi entropy principle. AB - We propose dynamics equations which describe the behaviour of non-stationary processes that follow the maximum Renyi entropy principle. The equations are derived on the basis of the speed-gradient principle originated in the control theory. The maximum of the Renyi entropy principle is analysed for discrete and continuous cases, and both a discrete random variable and probability density function (PDF) are used. We consider mass conservation and energy conservation constraints and demonstrate the uniqueness of the limit distribution and asymptotic convergence of the PDF for both cases. The coincidence of the limit distribution of the proposed equations with the Renyi distribution is examined. PMID- 26997887 TI - Formation of wave packets in the Ostrovsky equation for both normal and anomalous dispersion. AB - It is well known that the Ostrovsky equation with normal dispersion does not support steady solitary waves. An initial Korteweg-de Vries solitary wave decays adiabatically through the radiation of long waves and is eventually replaced by an envelope solitary wave whose carrier wave and envelope move with different velocities (phase and group velocities correspondingly). Here, we examine the same initial condition for the Ostrovsky equation with anomalous dispersion, when the wave frequency increases with wavenumber in the limit of very short waves. The essential difference is that now there exists a steady solitary wave solution (Ostrovsky soliton), which in the small-amplitude limit can be described asymptotically through the solitary wave solution of a nonlinear Schrodinger equation, based at that wavenumber where the phase and group velocities coincide. Long-time numerical simulations show that the emergence of this steady envelope solitary wave is a very robust feature. The initial Korteweg-de Vries solitary wave transforms rapidly to this envelope solitary wave in a seemingly non adiabatic manner. The amplitude of the Ostrovsky soliton strongly correlates with the initial Korteweg-de Vries solitary wave. PMID- 26997888 TI - One hundred years of complex dynamics. AB - Holomorphic dynamics has been a key area of study for 100 years. In this survey, we focus on the dynamics of rational functions. PMID- 26997889 TI - The birth of E8 out of the spinors of the icosahedron. AB - E8 is prominent in mathematics and theoretical physics, and is generally viewed as an exceptional symmetry in an eight-dimensional (8D) space very different from the space we inhabit; for instance, the Lie group E8 features heavily in 10D superstring theory. Contrary to that point of view, here we show that the E8 root system can in fact be constructed from the icosahedron alone and can thus be viewed purely in terms of 3D geometry. The 240 roots of E8 arise in the 8D Clifford algebra of 3D space as a double cover of the 120 elements of the icosahedral group, generated by the root system H3. As a by-product, by restricting to even products of root vectors (spinors) in the 4D even subalgebra of the Clifford algebra, one can show that each 3D root system induces a root system in 4D, which turn out to also be exactly the exceptional 4D root systems. The spinorial point of view explains their existence as well as their unusual automorphism groups. This spinorial approach thus in fact allows one to construct all exceptional root systems within the geometry of three dimensions, which opens up a novel interpretation of these phenomena in terms of spinorial geometry. PMID- 26997890 TI - Asymmetric collapse by dissolution or melting in a uniform flow. AB - An advection-diffusion-limited dissolution model of an object being eroded by a two-dimensional potential flow is presented. By taking advantage of the conformal invariance of the model, a numerical method is introduced that tracks the evolution of the object boundary in terms of a time-dependent Laurent series. Simulations of a variety of dissolving objects are shown, which shrink and collapse to a single point in finite time. The simulations reveal a surprising exact relationship, whereby the collapse point is the root of a non-analytic function given in terms of the flow velocity and the Laurent series coefficients describing the initial shape. This result is subsequently derived using residue calculus. The structure of the non-analytic function is examined for three different test cases, and a practical approach to determine the collapse point using a generalized Newton-Raphson root-finding algorithm is outlined. These examples also illustrate the possibility that the model breaks down in finite time prior to complete collapse, due to a topological singularity, as the dissolving boundary overlaps itself rather than breaking up into multiple domains (analogous to droplet pinch-off in fluid mechanics). The model raises fundamental mathematical questions about broken symmetries in finite-time singularities of both continuous and stochastic dynamical systems. PMID- 26997891 TI - Beam finite-element model of a molecular motor for the simulation of active fibre networks. AB - Molecular motors are proteins that excessively increase the efficiency of subcellular transport processes. They allow for cell division, nutrient transport and even macroscopic muscle movement. In order to understand the effect of motors in large biopolymer networks, e.g. the cytoskeleton, we require a suitable model of a molecular motor. In this contribution, we present such a model based on a geometrically exact beam finite-element formulation. We discuss the numerical model of a non-processive motor such as myosin II, which interacts with actin filaments. Based on experimental data and inspired by the theoretical understanding offered by the power-stroke model and the swinging-cross-bridge model, we parametrize our numerical model in order to achieve the effect that a physiological motor has on its cargo. To this end, we introduce the mechanical and mathematical foundations of the model, then discuss its calibration, prove its usefulness by conducting finite-element simulations of actin-myosin motility assays and assess the influence of motors on the rheology of semi-flexible biopolymer networks. PMID- 26997892 TI - Bright solitons in non-equilibrium coherent quantum matter. AB - We theoretically demonstrate a mechanism for bright soliton generation in spinor non-equilibrium Bose-Einstein condensates made of atoms or quasi-particles such as polaritons in semiconductor microcavities. We give analytical expressions for bright (half) solitons as minimizing functions of a generalized non-conservative Lagrangian elucidating the unique features of inter and intra-competition in non equilibrium systems. The analytical results are supported by a detailed numerical analysis that further shows the rich soliton dynamics inferred by their instability and mutual cross-interactions. PMID- 26997893 TI - Deformation of a micro-torque swimmer. AB - The membrane tension of some kinds of ciliates has been suggested to regulate upward and downward swimming velocities under gravity. Despite its biological importance, deformation and membrane tension of a ciliate have not been clarified fully. In this study, we numerically investigated the deformation of a ciliate swimming freely in a fluid otherwise at rest. The cell body was modelled as a capsule with a hyperelastic membrane enclosing a Newtonian fluid. Thrust forces due to the ciliary beat were modelled as torques distributed above the cell body. The effects of membrane elasticity, the aspect ratio of the cell's reference shape, and the density difference between the cell and the surrounding fluid were investigated. The results showed that the cell deformed like a heart shape, when the capillary number was sufficiently large. Under the influence of gravity, the membrane tension at the anterior end decreased in the upward swimming while it increased in the downward swimming. Moreover, gravity-induced deformation caused the cells to move gravitationally downwards or upwards, which resulted in a positive or negative geotaxis-like behaviour with a physical origin. These results are important in understanding the physiology of a ciliate's biological responses to mechanical stimuli. PMID- 26997894 TI - Origami tubes with reconfigurable polygonal cross-sections. AB - Thin sheets can be assembled into origami tubes to create a variety of deployable, reconfigurable and mechanistically unique three-dimensional structures. We introduce and explore origami tubes with polygonal, translational symmetric cross-sections that can reconfigure into numerous geometries. The tubular structures satisfy the mathematical definitions for flat and rigid foldability, meaning that they can fully unfold from a flattened state with deformations occurring only at the fold lines. The tubes do not need to be straight and can be constructed to follow a non-linear curved line when deployed. The cross-section and kinematics of the tubular structures can be reprogrammed by changing the direction of folding at some folds. We discuss the variety of tubular structures that can be conceived and we show limitations that govern the geometric design. We quantify the global stiffness of the origami tubes through eigenvalue and structural analyses and highlight the mechanical characteristics of these systems. The two-scale nature of this work indicates that, from a local viewpoint, the cross-sections of the polygonal tubes are reconfigurable while, from a global viewpoint, deployable tubes of desired shapes are achieved. This class of tubes has potential applications ranging from pipes and micro-robotics to deployable architecture in buildings. PMID- 26997895 TI - Critical assessment of hydrogen effects on the slip transmission across grain boundaries in alpha -Fe. AB - Grain boundaries (GBs) play a fundamental role in the strengthening mechanism of crystalline structures by acting as an impediment to dislocation motion. However, the presence of an aggressive environment such as hydrogen increases the susceptibility to intergranular fracture. Further, there is a lack of systematic investigations exploring the role of hydrogen on the dislocation-grain-boundary (DGB) interactions. Thus, in this work, the effect of hydrogen on the interactions between a screw dislocation and <111> tilt GBs in alpha-Fe were examined. Our simulations reveal that the outcome of the DGB interaction strongly depends on the underlying GB dislocation network. Further, there exists a strong correlation between the GB energy and the energy barrier for slip transmission. In other words, GBs with lower interfacial energy demonstrate a higher barrier for slip transmission. The introduction of hydrogen along the GB causes the energy barrier for slip transmission to increase consistently for all of the GBs examined. The energy balance for a crack initiation in the presence of hydrogen was examined with the help of our observations and previous findings. It was found that the presence of hydrogen increases the strain energy stored within the GB which could lead to a transgranular-to-intergranular fracture mode transition. PMID- 26997896 TI - Performances and robustness of quantum teleportation with identical particles. AB - When quantum teleportation is performed with truly identical massive particles, indistinguishability allows us to teleport addressable degrees of freedom which do not identify particles, but, for example, orthogonal modes. The key resource of the protocol is a state of entangled modes, but the conservation of the total number of particles does not allow for perfect deterministic teleportation unless the number of particles in the resource state goes to infinity. Here, we study the convergence of teleportation performances in the above limit and provide sufficient conditions for asymptotic perfect teleportation. We also apply these conditions to the case of resource states affected by noise. PMID- 26997898 TI - A curve shortening flow rule for closed embedded plane curves with a prescribed rate of change in enclosed area. AB - Motivated by a problem from fluid mechanics, we consider a generalization of the standard curve shortening flow problem for a closed embedded plane curve such that the area enclosed by the curve is forced to decrease at a prescribed rate. Using formal asymptotic and numerical techniques, we derive possible extinction shapes as the curve contracts to a point, dependent on the rate of decreasing area; we find there is a wider class of extinction shapes than for standard curve shortening, for which initially simple closed curves are always asymptotically circular. We also provide numerical evidence that self-intersection is possible for non-convex initial conditions, distinguishing between pinch-off and coalescence of the curve interior. PMID- 26997897 TI - Are some people suffering as a result of increasing mass exposure of the public to ultrasound in air? AB - New measurements indicate that the public are being exposed, without their knowledge, to airborne ultrasound. Existing guidelines are insufficient for such exposures; the vast majority refers to occupational exposure only (where workers are aware of the exposure, can be monitored and can wear protection). Existing guidelines are based on an insufficient evidence base, most of which was collected over 40 years ago by researchers who themselves considered it insufficient to finalize guidelines, but which produced preliminary guidelines. This warning of inadequacy was lost as nations and organizations issued 'new' guidelines based on these early guidelines, and through such repetition generated a false impression of consensus. The evidence base is so slim that few reports have progressed far along the sequence from anecdote to case study, to formal scientific controlled trials and epidemiological studies. Early studies reported hearing threshold shifts, nausea, headache, fatigue, migraine and tinnitus, but there is insufficient research on human subjects, and insufficient measurement of fields, to assess what health risk current occupational and public exposures might produce. Furthermore, the assumptions underpinning audiology and physical measurements at high frequencies must be questioned: simple extrapolation of approaches used at lower frequencies does not address current unknowns. Recommendations are provided. PMID- 26997899 TI - Quantum asymmetry between time and space. AB - An asymmetry exists between time and space in the sense that physical systems inevitably evolve over time, whereas there is no corresponding ubiquitous translation over space. The asymmetry, which is presumed to be elemental, is represented by equations of motion and conservation laws that operate differently over time and space. If, however, the asymmetry was found to be due to deeper causes, this conventional view of time evolution would need reworking. Here we show, using a sum-over-paths formalism, that a violation of time reversal (T) symmetry might be such a cause. If T symmetry is obeyed, then the formalism treats time and space symmetrically such that states of matter are localized both in space and in time. In this case, equations of motion and conservation laws are undefined or inapplicable. However, if T symmetry is violated, then the same sum over paths formalism yields states that are localized in space and distributed without bound over time, creating an asymmetry between time and space. Moreover, the states satisfy an equation of motion (the Schrodinger equation) and conservation laws apply. This suggests that the time-space asymmetry is not elemental as currently presumed, and that T violation may have a deep connection with time evolution. PMID- 26997900 TI - Fragmentation as an aggregation process: the role of defects. AB - A cohesive object will eventually break into fragment when experiencing a strong deformation, during an impact for instance. Using necklaces of cohesive magnetized spheres suddenly expanded, we have shown that the fragmentation of this one-dimensional material results from an inverse aggregation cascade (Vledouts et al. 2015 Proc. R. Soc. A 471, 20150678. (doi:10.1098/rspa.2015.0678)). Here, we explore a variant of this process by changing the force law between the attracting spheres, using hydrogel beads linked by capillary bridges. We also investigate the role of (weak) defects in the cohesion strength and the consequences of a distribution of forces between the beads. It is found that fragment do form by a cascade of aggregations, which is interrupted earlier when the force disorder is stronger. PMID- 26997901 TI - Deformation compatibility in a single crystalline Ni superalloy. AB - Deformation in materials is often complex and requires rigorous understanding to predict engineering component lifetime. Experimental understanding of deformation requires utilization of advanced characterization techniques, such as high spatial resolution digital image correlation (HR-DIC) and high angular resolution electron backscatter diffraction (HR-EBSD), combined with clear interpretation of their results to understand how a material has deformed. In this study, we use HR DIC and HR-EBSD to explore the mechanical behaviour of a single-crystal nickel alloy and to highlight opportunities to understand the complete deformations state in materials. Coupling of HR-DIC and HR-EBSD enables us to precisely focus on the extent which we can access the deformation gradient, F , in its entirety and uncouple contributions from elastic deformation gradients, slip and rigid body rotations. Our results show a clear demonstration of the capabilities of these techniques, found within our experimental toolbox, to underpin fundamental mechanistic studies of deformation in polycrystalline materials and the role of microstructure. PMID- 26997902 TI - Neutron reflectometry on highly absorbing films and its application to 10B4C based neutron detectors. AB - Neutron reflectometry is a powerful tool used for studies of surfaces and interfaces. The absorption in the typical studied materials is neglected and this technique is limited only to the reflectivity measurement. For strongly absorbing nuclei, the absorption can be directly measured by using the neutron-induced fluorescence technique which exploits the prompt particle emission of absorbing isotopes. This technique is emerging from soft matter and biology where highly absorbing nuclei, in very small quantities, are used as a label for buried layers. Nowadays, the importance of absorbing layers is rapidly increasing, partially because of their application in neutron detection; a field that has become more active also due to the 3He-shortage. We extend the neutron-induced fluorescence technique to the study of layers of highly absorbing materials, in particular 10B4C. The theory of neutron reflectometry is a commonly studied topic; however, when a strong absorption is present the subtle relationship between the reflection and the absorption of neutrons is not widely known. The theory for a general stack of absorbing layers has been developed and compared to measurements. We also report on the requirements that a 10B4C layer must fulfil in order to be employed as a converter in neutron detection. PMID- 26997903 TI - On firework blasts and qualitative parameter dependency. AB - In this paper, a mathematical model is developed to qualitatively simulate the progressive time-evolution of a blast from a simple firework. Estimates are made for the blast radius that one can expect for a given amount of detonation energy and pyrotechnic display material. The model balances the released energy from the initial blast pulse with the subsequent kinetic energy and then computes the trajectory of the material under the influence of the drag from the surrounding air, gravity and possible buoyancy. Under certain simplifying assumptions, the model can be solved for analytically. The solution serves as a guide to identifying key parameters that control the evolving blast envelope. Three dimensional examples are given. PMID- 26997904 TI - Dynamic growth of slip surfaces in catastrophic landslides. AB - This work considers a landslide caused by the shear band that emerges along the potential slip (rupture) surface. The material above the band slides downwards, causing the band to grow along the slope. This growth may first be stable (progressive), but eventually becomes dynamic (catastrophic). The landslide body acquires a finite velocity before it separates from the substrata. The corresponding initial-boundary value problem for a dynamic shear band is formulated within the framework of Palmer & Rice's (Proc. R. Soc. Lond. A332, 527 548. (doi:10.1098/rspa.1973.0040)) approach, which is generalized to the dynamic case. We obtain the exact, closed-form solution for the band velocity and slip rate. This solution assesses when the slope fails owing to a limiting condition near the propagating tip of the shear band. Our results are applicable to both submarine and subaerial landslides of this type. It appears that neglecting dynamic (inertia) effects can lead to a significant underestimation of the slide size, and that the volumes of catastrophic slides can exceed the volumes of progressive slides by nearly a factor of 2. As examples, we consider the Gaviota and Humboldt slides offshore of California, and discuss landslides in normally consolidated sediments and sensitive clays. In particular, it is conceivable that Humboldt slide is unfinished and may still displace a large volume of sediments, which could generate a considerable tsunami. We show that in the case of submarine slides, the effect of water resistance on the shear band dynamics may frequently be limited during the slope failure stage. For a varying slope angle, we formulate a condition of slide cessation. PMID- 26997905 TI - Consent Under Pressure: The Puzzle of Third Party Coercion. PMID- 26997906 TI - A maximum Likelihood Approach to Analyzing Incomplete Longitudinal Data in Mammary Tumor Development Experiments with Mice. AB - Longitudinal mammary tumor development studies using mice as experimental units are affected by i) missing data towards the end of the study by natural death or euthanasia, and ii) the presence of censored data caused by the detection limits of instrumental sensitivity. To accommodate these characteristics, we investigate a test to carry out K-group comparisons based on maximum likelihood methodology. We derive a relevant likelihood ratio test based on general distributions, investigate its properties of based on theoretical propositions, and evaluate the performance of the test via a simulation study. We apply the results to data extracted from a study designed to investigate the development of breast cancer in mice. PMID- 26997907 TI - EVALUATION OF THE EXTRACELLULAR MATRIX OF INJURED SUPRASPINATUS IN RATS. AB - OBJECTIVE: To evaluate the evolution of injuries of the supraspinatus muscle by immunohistochemistry (IHC) and anatomopathological analysis in animal model (Wistar rats). METHODS: Twenty-five Wistar rats were submitted to complete injury of the supraspinatus tendon, then subsequently sacrificed in groups of five animals at the following periods: immediately after the injury, 24h after the injury, 48h after, 30 days after and three months after the injury. All groups underwent histological and IHC analysis. RESULTS: Regarding vascular proliferation and inflammatory infiltrate, we found a statistically significant difference between groups 1(control group) and 2 (24h after injury). IHC analysis showed that expression of vascular endothelial growth factor (VEGF) showed a statistically significant difference between groups 1 and 2, and collagen type 1 (Col-1) evaluation presented a statistically significant difference between groups 1 and 4. CONCLUSION: We observed changes in the extracellular matrix components compatible with remodeling and healing. Remodeling is more intense 24h after injury. However, VEGF and Col-1 are substantially increased at 24h and 30 days after the injury, respectively. Level of Evidence I, Experimental Study. PMID- 26997908 TI - STUDIES OF MOLECULAR CHANGES IN INTERVERTEBRAL DISC DEGENERATION IN ANIMAL MODEL. AB - OBJECTIVE: To evaluate the structural and molecular changes in the extracellular matrix (ECM) during the process of intervertebral disc degeneration, using animal model. METHODS: Wistar rats underwent intervertebral disc degeneration through 20 gauge needle puncture, and 360 degrees rotation applied for 30 sec, representing the degenerated group, while control group was not submitted to this procedure. Histological parameters and expression of extracellular matrix molecules were evaluated in the 15(th) and 28(th) days after degenerative induction. RESULTS: Fifteen days after the induction of intervertebral disc degeneration, significant changes were observed, such as reduction in the expression metalloprotease-9 (MMP9) and interleukins (IL-6 and IL-10). There was a significant increase in the expression of vascular endothelial growth factor (VEGF) and caspase-3. However, different alterations in the ECM were observed at 28 days, the level of collagen I, metalloprotease-2 (MMP2) and caspase-3 were enhanced. Furthermore, expression of heparanase isoforms (HPSE1 and HPSE2) mRNA were increased in the degenerative intervertebral disc. CONCLUSION: The different profiles of ECM molecules observed during the intervertebral disc degeneration suggest that molecular processes such as ECM remodeling, neovascularization, apoptosis and inflammation occur. Experimental Study. PMID- 26997909 TI - KNEE ARTHROPLASTY REVISION WITH A CONSTRAINED IMPLANT USING HINGE AND ROTATING TIBIAL BASIS. AB - OBJECTIVE: To evaluate the results of total knee arthoplasty revisions performed in high complexity cases, with large bone defects or serious ligament deficiencies using a constrained implant hinge associated to a rotating tibial basis. METHODS: We evaluated 11 patients in which we used the constrained implant hinge associated to rotating tibial basis, with minimum follow-up of two years. The indications for the procedure included instability, septic loosening, late postoperative infection without loosening and periprosthetic fracture. We evaluated the knee range of movement and functional outcomes by the Knee Society Score (KSS) e Knee Injury and Osteoarthritis Outcome Score (KOOS), besides the presence of complications. RESULTS: All patients achieved 5(o) to 85(o) minimum range of motion at 1 year postoperatively and, in the present evaluation, KSS ranged from 67 to 95. Three patients had no complications until the last evaluation and two patients required implant revision. CONCLUSION: Despite the complications rate observed, the functional result were acceptable for most patients, and it proved being a viable alternative, especially for patients with low functional demand. Level of Evidence IV, Case Series. PMID- 26997911 TI - ARTHROSCOPIC TREATMENT OF OSTEOCHONDRAL LESIONS OF THE TALUS. AB - OBJECTIVE: To assess pain and function of the ankle in patients with injuries up to 1.5 cm diameter by the American Orthopaedic Foot and Ankle Society (AOFAS) score after arthroscopic treatment. METHODS: The AOFAS scale was applied before and after arthroscopy, as well as the degree of subjective satisfaction of ambulatory patients. Patients with type I osteochondral injuries, acute trauma, using plaster, presenting lesions in other joints of the lower limbs and cognitive impairment that would prevent the application of the satisfaction questionnaire were excluded from the study. Statistical analysis was performed using unpaired t test with Welch correction, Mann Whitney test, and ANOVA, with Kruskal Wallis test and Dun test, considering p value lower than 0.05. RESULTS: There was an increased AOFAS scores after arthroscopic treatment in 52 (94.5%) patients. The mean values of AOFAS score in 55 patients was 77.32 +/- 6.67 points preoperative and 93.10+/- 8.24 points postoperative, with a mean variation of 15.8 points, p<0.001. Patients with stage II, III and IV injuries showed an increased AOFAS scores after arthroscopic treatment, p<0.001. No difference was found between medial and lateral injuries, p >0.05. CONCLUSION: Patients with stage II, III or IV osteochondral injuries of the talus of up to 1.5 cm diameter, whether medial or lateral, showed a significant improvement after arthroscopic treatment. Level of Evidence III, Retrospective Study. PMID- 26997910 TI - DOES RECTUS FEMORIS TRANSFER INCREASE KNEE FLEXION DURING STANCE PHASE IN CEREBRAL PALSY? AB - OBJECTIVE: To evaluate whether distal rectus femoris transfer (DRFT) is related to postoperative increase of knee flexion during the stance phase in cerebral palsy (CP). METHODS: The inclusion criteria were Gross Motor Function Classification System (GMFCS) levels I-III, kinematic criteria for stiff-knee gait at baseline, and individuals who underwent orthopaedic surgery and had gait analyses performed before and after intervention. The patients included were divided into the following two groups: NO-DRFT (133 patients), which included patients who underwent orthopaedic surgery without DRFT, and DRFT (83 patients), which included patients who underwent orthopaedic surgery that included DRFT. The primary outcome was to evaluate in each group if minimum knee flexion in stance phase (FMJFA) changed after treatment. RESULTS: The mean FMJFA increased from 13.19 degrees to 16.74 degrees (p=0.003) and from 10.60 degrees to 14.80 degrees (p=0.001) in Groups NO-DRFT and DRFT, respectively. The post-operative FMJFA was similar between groups NO-DRFT and DRFT (p=0.534). The increase of FMJFA during the second exam (from 13.01 degrees to 22.51 degrees ) was higher among the GMFCS III patients in the DRFT group (p<0.001). CONCLUSION: In this study, DRFT did not generate additional increase of knee flexion during stance phase when compared to the control group. Level of Evidence III, Retrospective Comparative Study. PMID- 26997912 TI - COMPARATIVE STUDY OF MICROANASTOMOSIS WITH DISTINCT 10-0 NYLON SUTURES IN RATS. AB - OBJECTIVE: The aim of this study is to compare micro-sutures commonly used in our midst. METHODS: In this double-blind study, 30 Wistar rats were operated randomly divided into three groups matched according to the suture used (Nylon 10-0, 75micron, brands Microsuture((r)), Polysuture((r)) and Ethicon((r))). We analyzed the number of surgical nodes required, bleeding, surgical time and histological evaluation. RESULTS: There was no significant difference between the amount of stitches of arterial suture per anastomosis. Surgical time was longer in Microsuture((r)) group as compared to Polysuture((r)) (p <= 0.05). Bleeding in Microsuture((r)) group was higher when compared to the others (p <0.01). In the histological analysis, the Microsuture((r)) group showed a greater tendency to develop fibrosis and aneurysm in surgical site than the others (p <0.01 and p<=0,05, respectively). Similarly, the Ethicon((r)) group showed less tendency to myointimal proliferation than the rest. (p = 0.025). CONCLUSION: The results confirm the relevance of the choice of surgical thread as an independent determining factor for the success of the procedure, besides serving as a rational subsidy for a better cost-benefit analysis. Level of Evidence I, Experimental Study, Controlled Animal Study. PMID- 26997913 TI - EFFECT OF SECOND TOE-TO-HAND TRANSFER ON THE PLANTAR PRESSURE DISTRIBUTION OF THE DONOR FOOT. AB - OBJECTIVE: To investigate the effect of second toe-to-hand transfer on the plantar pressure distribution of the donor foot. METHODS: Twelve normal fresh frozen cadaveric foot specimens were subjected to an axial load of 600 N. An F Scan plantar pressure analysis system was used to measure the forefoot plantar pressure. The testing was performed under the conditions of intact second toe, second toe removal with the second metatarsal head reserved, and second toe removal in combination with the distal one-third of the second metatarsal, respectively. RESULTS: The peak pressure of the second metatarsal head was greater than other four forefoot plantar regions. There was no statistically significant change in the forefoot plantar pressure distribution after the second toe was removed (p > 0.05). When the second toe and the distal one-third of the second metatarsal were removed, the forefoot plantar pressure distribution changed significantly (p < 0.05). CONCLUSIONS: An intact second metatarsal is essential for the normal distribution of plantar pressure. Removal of the second toe with the second metatarsal head reserved had little influence on the plantar pressure distribution of the donor foot. Removal of the second toe and distal one third of the second metatarsal resulted in abnormal plantar pressure distribution. Level of Evidence II, Experimental Study. PMID- 26997914 TI - CLINICAL OUTCOME AFTER INFECTED TOTAL KNEE AND TOTAL HIP ARTHROPLASTY. AB - OBJECTIVE: Infection after total hip (THA) and knee arthroplasty (TKA) is a serious complication which typically leads to a long lasting and intensive surgical and medicamentous treatment. The aim of this study was to identify factors that influence outcome after revision surgery caused by prosthetic infection. METHODS: We retrospectively analyzed 64 patients who had revision surgery between 1989 and 2009 due to periprosthetic infection. We examined a total of 69 joints (TKA: 36%, THA: 64%), follow-up 5.1 years (0.5-21 years) after the initial surgical intervention. The mean patient age at time of surgery was 67 years old (43-79 years old). Clinical data and scores including the Western Ontario and McMaster Universities (WOMAC)-Index, the Harris Hip Score (HHS) and the Hospital for Special Surgery Score (HSS) were surveyed. RESULTS: There was no difference in clinical scores regarding treatment between a single and a multiple stage treatment regime. Infections with multiple microorganisms and Enterococcus spp. lead to a significantly higher number of interventions. Using a modified Tsukayama system we classified 24% as type I, 34% type II and 42% type III- infections, with no differences in clinical outcome. Overweight patients had a significantly lower HHS and WOMAC-score. Immunosuppression leads to a worse WOMAC and HSS-Score. An increased number of procedures was associated to a limping gait. CONCLUSION: Thorough surgical technique leads to good clinical results independent of infection-type and treatment philosophy. Level of Evidence III, Case Control Study. PMID- 26997915 TI - EPIDEMIOLOGY AND TREATMENT OF MONTEGGIA LESION IN ADULTS: SERIES OF 44 CASES. AB - OBJECTIVE: To analyze the epidemiology, treatment and outcome of a series of adult patients with Monteggia lesion treated in Uruguayan institutions. METHODS: This is a retrospective article, we retrospectively identified from two Uruguayan institutions 44 adult patients with Monteggia lesion and analyzed their characteristics including Bado classification, associated injuries, treatment modality and outcome (Morrey score). RESULTS: Using Bado classification, 23 cases (52%) were type II, 12 (27%) type I, seven (16%) type IV and two cases (5%) type III. Associated lesions were radial head fractures, found in 15 patients, coronoid ipsilateral fractures in seven patients, and neurological injuries in four. Radial head dislocation was reduced in 93% of the cases with closed maneuvers. Ulna fractures underwent open reduction and internal fixation in all 30 cases using 3.5 mm DCP plates. Complications after surgery occurred in 21 cases. Revision surgery was done in 15 cases. Outcomes after primary and revision surgery were good or excellent in 37 cases. CONCLUSIONS: In our series we observed that Monteggia lesion in adults is a serious injury with a high number of complications that often require revision surgeries. Level of Evidence IV, Retrospective Study, Case Series. PMID- 26997916 TI - VISCOSUPPLEMENTATION IN ANKLE OSTEOARTHRITIS: A SYSTEMATIC REVIEW. AB - To evaluate the efficacy of viscosupplementation in patients with osteoarthritis of the ankle. A systematic review to evaluate the evidence in the literature on the use of viscosupplementation for osteoarthritis of the ankle. For this review, we considered blind randomized prospective studies involving the use of viscosupplementation for osteoarthritis of the ankle. A total of 1,961 articles were identified in various databases. After examining each of the articles, five articles were included in this review. Treatment with intraarticular hyaluronic acid is a safe treatment modality that significantly improves functional scores of patients, with no evidence of superiority in relation to other conservative treatments. Further clinical trials with larger numbers of patients are needed so that we can recommend its use and address unanswered questions . Systematic Review of Randomized Clinical Trials. PMID- 26997917 TI - The Effect of Stand-biased Desks on Academic Engagement: An Exploratory Study. AB - BACKGROUND: Schools have been suggested as a viable avenue to combat childhood obesity. School administrators are sometimes faced with the conflicting demands of improving the health of their students and maintaining academic performance. Dynamic furniture such as stand-biased desks may be one way to address both academic and health demands placed on schools to prevent childhood obesity. METHOD: Classrooms with stand-biased desks were compared to classrooms using traditional seated desks in 2nd,3rd, and 4th grades. The academic engagement of 282 participants was observed in the fall and spring during one academic year. The engagement of the treatment classrooms was compared to the engagement of the control classrooms. RESULTS: Both groups showed general increases in their academic engagement over time. Stand-biased desks do not seem to result in adverse effects on academic engagement when used in elementary classrooms. CONCLUSION: The data suggests promising results for the use of stand-biased desks in elementary school classrooms. The results suggest that stand-biased desks can be introduced in the classroom to combat childhood obesity through increasing energy expenditure without affecting academic engagement. PMID- 26997918 TI - The future of stem cell therapy for stroke rehabilitation. PMID- 26997919 TI - A Modified Coupled Spectrophotometric Method to Detect 2-5 Oligoadenylate Synthetase Activity in Prostate Cell Lines. AB - BACKGROUND: 2'-5' oligoadenylate synthetases (OAS) are interferon inducible enzymes that polymerizes ATP to 2'-5'-linked oligomers of adenylate (2-5As). As part of the innate immune response, these enzymes are activated by viral double stranded RNA or mRNAs with significant double stranded structure. The 2-5As in turn activate RNaseL that degrade single stranded RNAs. Three distinct forms of OAS exist in human cells (OAS1, 2 and 3) with each form having multiple spliced variants. The OAS enzymes and their spliced variants have different enzyme activities. OAS enzymes also play a significant role in regulating multiple cellular processes such as proliferation and apoptosis. Moreover, Single nucleotide polymorphisms that alter OAS activity are also associated with viral infection, diabetes and cancer. Thus detection of OAS enzyme activity with a simple spectrophotometric method in cells will be important in clinical research. RESULTS: Here we propose a modified coupled spectrophotometric assay to detect 2 5 oligoadenylate synthetase (OAS) enzyme activity in prostate cell lines as a model system. The OAS enzyme from prostate cancer cell lysates was purified using Polyinosinic: polycytidylic acid (poly I:C) bound activated sepharose beads. The activated OAS enzyme eluted from Sepharose beads showed expression of p46 isoform of OAS1, generally considered the most abundant OAS isoform in elutes from DU14 cell line but not in other prostate cell line. In this assay the phosphates generated by the OAS enzymatic reaction is coupled with conversion of the substrate 2-amino-6-mercapto-7-methylpurine ribonucleoside (methylthioguanosine, a guanosine analogue; MESG) to a purine base product, 2-amino-6-mercapto-7 methylpurine and ribose1-phosphate via a catalyst purine nucleoside phosphorylase (phosphorylase) using a commercially available pyrophosphate kit. The absorbance of the purine base product is measured at 360 nm. The higher levels of phosphates detected in DU145 cell line indicates more activity of OAS in this prostate cancer cell line. CONCLUSION: The modified simple method detected OAS enzyme activity with sensitivity and specificity, which could help in detection of OAS enzymes avoiding the laborious and radioactive methods. PMID- 26997921 TI - Mobile Tech and the Librarian: The iTest iPad Project. AB - A 2012 project provided forty-eight health sciences librarians from primarily hospital and academic health sciences libraries with an Apple iPad2 along with training and support on its use. Project objectives were to determine how participants would adopt the iPad into their daily operations and what form of leadership role they would play while participating in the project. By project's end eighty-nine percent indicated they would continue using the iPad primarily as a productivity tool and to provide point of need services. Project data indicated that librarians assumed a leadership role promoting the use of mobile technology and the applications available. PMID- 26997920 TI - Maximizing Wellness in Successful Aging and Cancer Coping: The Importance of Family Communication from a Socioemotional Selectivity Theoretical Perspective. AB - Interpersonal communication is a fundamental part of being and key to health. Interactions within family are especially critical to wellness across time. Family communication is a central means of adaptation to stress, coping, and successful aging. Still, no theoretical argument in the discipline exists that prioritizes kin communication in health. Theoretical advances can enhance interventions and policies that improve family life. This article explores socioemotional selectivity theory (SST), which highlights communication in our survival. Communication partner choice is based on one's time perspective, which affects our prioritization of goals to survive-goals sought socially. This is a first test of SST in a family communication study on women's health and aging. More than 300 women of varying ages and health status participated. Two time factors, later adulthood and late-stage breast cancer, lead women to prioritize family communication. Findings provide a theoretical basis for prioritizing family communication issues in health reform. PMID- 26997922 TI - Cross-Validation of Survival Bump Hunting by Recursive Peeling Methods. AB - We introduce a survival/risk bump hunting framework to build a bump hunting model with a possibly censored time-to-event type of response and to validate model estimates. First, we describe the use of adequate survival peeling criteria to build a survival/risk bump hunting model based on recursive peeling methods. Our method called "Patient Recursive Survival Peeling" is a rule-induction method that makes use of specific peeling criteria such as hazard ratio or log-rank statistics. Second, to validate our model estimates and improve survival prediction accuracy, we describe a resampling-based validation technique specifically designed for the joint task of decision rule making by recursive peeling (i.e. decision-box) and survival estimation. This alternative technique, called "combined" cross-validation is done by combining test samples over the cross-validation loops, a design allowing for bump hunting by recursive peeling in a survival setting. We provide empirical results showing the importance of cross-validation and replication. PMID- 26997923 TI - Conceptual Foundations of Diffusion in Magnetic Resonance. AB - A thorough review of the q-space technique is presented starting from a discussion of Fick's laws. The work presented here is primarily conceptual, theoretical and hopefully pedagogical. We offered the notion of molecular concentration to unify Fick's laws and diffusion MRI within a coherent conceptual framework. The fundamental relationship between diffusion MRI and the Fick's laws are carefully established. The conceptual and theoretical basis of the q-space technique is investigated from first principles. PMID- 26997924 TI - RARtool: A MATLAB Software Package for Designing Response-Adaptive Randomized Clinical Trials with Time-to-Event Outcomes. AB - Response-adaptive randomization designs are becoming increasingly popular in clinical trial practice. In this paper, we present RARtool, a user interface software developed in MATLAB for designing response-adaptive randomized comparative clinical trials with censored time-to-event outcomes. The RARtool software can compute different types of optimal treatment allocation designs, and it can simulate response-adaptive randomization procedures targeting selected optimal allocations. Through simulations, an investigator can assess design characteristics under a variety of experimental scenarios and select the best procedure for practical implementation. We illustrate the utility of our RARtool software by redesigning a survival trial from the literature. PMID- 26997925 TI - The Rescue and Repurposing of Pharmaceuticals: Augmenting the Drug Development Paradigm. PMID- 26997926 TI - Hypertonic Saline for the Treatment of Bronchiolitis in Infants and Young Children: A Critical Review of the Literature. AB - Bronchiolitis, an infection of the lower respiratory tract, is the leading cause of infant and child hospitalization in the United States. Therapeutic options for management of bronchiolitis are limited. Hypertonic saline inhalation therapy has been studied in numerous clinical trials with mixed results. In 2014, the American Academy of Pediatrics (AAP) published updated guidelines on the diagnosis and management of bronchiolitis, which include new recommendations on the use of hypertonic saline. We reviewed all published clinical trials mentioned in the 2014 AAP guidelines, as well as additional trials published since the guidelines, and critically evaluated each trial to determine efficacy, safety, and expectations of hypertonic saline inhalation therapy. A total of 2682 infants were studied over the course of 22 clinical trials. Nine trials were carried out in the outpatient/clinic/emergency department and 13 in the inpatient setting. We agree with the AAP guidelines regarding the recommendation to use nebulized hypertonic saline for infants hospitalized with bronchiolitis, with the expectation of reducing bronchiolitis scores and length of stay when it is expected to last more than 72 hours. However, we also believe there might be an advantage for hypertonic saline in reducing admission rates from the emergency department, based on close examination of the results of recent trials. This review also highlights important gaps in the available literature that need to be addressed in order to define the role of inhaled hypertonic saline therapy. PMID- 26997927 TI - A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens. AB - This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7 valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13 valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines. PMID- 26997929 TI - Impact of a Standardized Treatment Guideline for Pediatric Iatrogenic Opioid Dependence: A Quality Improvement Initiative. AB - OBJECTIVES: To determine whether utilization of a hospital-based clinical practice guideline for the care of pediatric iatrogenic opioid dependence (IOD) would promote a decrease in opioid exposure and improve management of opioid abstinence syndrome (AS). METHODS: This study is a retrospective chart review of critically ill patients from a tertiary care children's hospital. Inclusion criteria included mechanically ventilated patients up to 18 years of age who received continuous opioid infusions for at least 7 days and any length of methadone administration. Data on IOD patients from January 2005 to June 2010 was divided into 3 periods: baseline, phase 1, and phase 2. Primary outcome was decrease in opioid exposure, measured by methadone duration of use and any additional opioid bolus doses used in AS management. Documentation of additional opioid bolus doses was regarded as a surrogate measure of AS. Secondary outcomes included total cumulative fentanyl dose, continuous fentanyl infusion duration of use, and hospital and pediatric intensive care unit length of stay. RESULTS: There was a significant decrease in methadone duration of use in IOD patients from 15.3 +/- 8.7 days at baseline to 9.5 +/- 3.7 days during phase 1 (p = 0.002), to 8.1 +/- 3.7 days on phase 2 (reduction not significant, p = 0.106) of this evaluation. Additional opioid bolus doses were significantly lower from baseline to phase 1 (5.5 +/- 5.1 vs. 1.8 +/- 2.3, p = 0.001) and from phase 1 to phase 2 (1.8 +/- 2.3 vs. 0.2 +/- 1.5, p = 0.003). For the remaining outcomes, differences were not observed among the evaluation periods, except for the total cumulative fentanyl dose, which was reduced from 2.8 +/- 3.7 mg/kg at baseline to 1 +/- 1 mg/kg only during phase 1 (p = 0.017). CONCLUSIONS: Introduction of a standardized, hospital-based clinical practice guideline for children with IOD reduced the length of exposure to opioids and improved opioid AS management. PMID- 26997928 TI - Medication Repurposing in Pediatric Patients: Teaching Old Drugs New Tricks. AB - OBJECTIVES: Gaps in pediatric therapeutics often result in off-label use and specifically, novel uses for existing medications, termed "drug repurposing." Drug Information (DI) queries to a Pediatric Medication Resource Center of a large metropolitan pediatric hospital in New York and inherent difficulties in retrieving evidence-based information prompted a review of current medication repurposing for pediatric patients. The objective included characterization of innovative off-label use of medications Food and Drug Administration (FDA) approved for 1 or more indications to treat a totally different disorder or indication in pediatric patients. METHODS: A systematic literature review was conducted to retrieve publications describing repurposed medications in pediatric patients. Excluded was FDA-approved indications used off-label in pediatric patients (e.g., different dose), preclinical data, adult use only, and experimental use. Evidence quality was classified using a modified American Academy of Neurology Level of Evidence. Results were analyzed using chi(2) at p < 0.05. RESULTS: Over 2000 references were retrieved and reviewed. A total of 101 medications repurposed for novel off-label uses for pediatric patients were identified: 38 for neonates, 74 for children, and 52 for adolescents. Neonates and infants were least likely to receive a medication for a repurposed use. Strong or intermediate evidence existed in 80.2% of cases. The evidence was weak in 19.8%. No significant relationship was observed between the pediatric age group and strength of the literature. Most repurposed uses pertained to generic or widely used medications. Less than 5% of medications were first marketed after 2011. CONCLUSIONS: While not exhaustive, the present study represents the most comprehensive listing of novel uses exclusive to pediatric patients. Further research is needed to identify the frequency of repurposed uses. The valuable DI role of pharmacists in assessing repurposed uses is of expanding and increasing importance to ensure such uses are evidence-based. PMID- 26997931 TI - Evaluation of Measuring Devices Packaged With Prescription Oral Liquid Medications. AB - OBJECTIVES: The US Food and Drug Administration industry guidelines for manufacturers of oral, over-the-counter, liquid medications recommend that these products be packaged with dosage-delivery devices. This study describes the prevalence of these devices and instructions packaged with prescription, oral, liquid medications. METHODS: This was a descriptive study of prescription oral liquid medications dispensed during a 6-month period at a community pharmacy. Product information was obtained from the National Library of Medicine's DailyMed database and from the products themselves. Endpoints included provision of a measuring device, the type of device, the maximum dose measurable and intervals on the provided device, and inclusion of instructions to the pharmacist. RESULTS: A total of 382 liquid prescription medications were included in the study. Forty nine of the 382 products (12.8%) were packaged with a measuring device. The most commonly provided device was a calibrated dropper (n = 18; 36.7%), followed by an oral syringe with a bottle adaptor (n = 9, 18.4%). Specific instructions on proper use of the provided measuring device were included with 20 products (40.8%). Among the products that did not provide a measuring device, only 70 of the 333 package inserts (21%) included instructions to the pharmacist regarding counseling the patient on proper administration. CONCLUSIONS: Packaging of prescription oral-liquid medications is inconsistent and leaves room for vast variability in patient or parent administration practices. In the future, patterns of actual dispensing practices among pharmacies and pharmacists would help determine the true incidence of dispensing of measuring devices. PMID- 26997930 TI - Vancomycin Dosing and Pharmacokinetics in Postoperative Pediatric Cardiothoracic Surgery Patients. AB - OBJECTIVES: This study compared vancomycin trough concentrations and pharmacokinetic parameters in pediatric cardiothoracic surgery (CTS) patients versus those in controls receiving 20 mg/kg/dose, intravenously, every 8 hours. METHODS: A retrospective study was conducted in children <18 years of age, following CTS, versus an age-and sex-matched control group. The primary objective was to determine differences in trough concentrations between groups. Secondary objectives included comparisons of pharmacokinetics between groups and development of vancomycin-associated acute kidney injury (AKI), defined as a doubling in serum creatinine from baseline. Also dosing projections were developed to target an area-under-the-curve-to-minimum inhibitory concentration (AUC:MIC) ratio of >=400. RESULTS: Twenty-seven patients in each group were evaluated. Mean trough concentrations were significantly different between groups (CTS: 18.4 mg/L; control: 8.8 mg/L; p < 0.01). Vancomycin-associated acute kidney injury AKI was significantly higher in the CTS group than in controls (25.9% versus 0%, respectively, p<0.01). There were significant differences in vancomycin elimination rates, with a high degree of variability, but no statistical differences in other parameters. Based on dosing projections, CTS patients would require 21 to 88 mg/kg/day, with a dosage interval determined by the child's glomerular filtration rate to achieve the target AUC:MIC >=400. CONCLUSIONS: Vancomycin dosage of 20 mg/kg/dose intravenously every 8 hours achieved significantly higher trough concentrations in CTS patients than in controls. Pharmacokinetic parameters were highly variable in CTS patients, indicating more individualization of dosage is needed. A future prospective study is needed to determine whether the revised dosage projections achieve the AUC:MIC target and to determine whether these regimens are associated with less vancomycin-associated AKI. PMID- 26997932 TI - Acute Pustular Dermatosis, Following Topical Treatment With Pimecrolimus, in a Child Affected With Atopic and Contact Hand Dermatitis. AB - Atopic dermatitis is considered an important risk factor for chronic hand dermatitis, which can be seen in children too. Pimecrolimus cream 1% is approved to treat atopic dermatitis in children aged 2 years or older. In adults, this drug has been used for some clinical indications other than atopic dermatitis, such as chronic hand dermatitis. Here, we describe an adverse drug reaction in a 2-year-old child affected with atopic dermatitis, who was treated with topical pimecrolimus in order to ameliorate her concomitant hand dermatitis. The use of topical pimecrolimus led to a previously undescribed hand pustular dermatosis, being consistent with a form of pustular leukocytoclastic vasculitis, which required the permanent discontinuation of topical pimecrolimus. PMID- 26997933 TI - Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report. AB - Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insulin infusion with insulin aspart. Allergic reactions to insulin detemir and insulin glargine have both been well described, with insulin detemir allergy appearing to be more common. There are several potential mechanisms for insulin allergy, and immunologic characteristics vary among different insulin analogs. After confirming insulin allergy in practice, management involves treating symptoms and switching insulin preparations. This is the first documented case of allergies to both insulin glargine and insulin detemir in a pediatric patient. Exact mechanism of insulin allergy is unknown, and management strategies must be individualized for each patient. PMID- 26997935 TI - Pediatric News. PMID- 26997934 TI - Pharmacokinetics of Continuous Infusion Meropenem With Concurrent Extracorporeal Life Support and Continuous Renal Replacement Therapy: A Case Report. AB - Pharmacokinetic parameters can be significantly altered for both extracorporeal life support (ECLS) and continuous renal replacement therapy (CRRT). This case report describes the pharmacokinetics of continuous-infusion meropenem in a patient on ECLS with concurrent CRRT. A 2.8-kg, 10-day-old, full-term neonate born via spontaneous vaginal delivery presented with hypothermia, lethargy, and a ~500-g weight loss from birth. She progressed to respiratory failure on hospital day 2 (HD 2) and developed sepsis, disseminated intravascular coagulation, and liver failure as a result of disseminated adenoviral infection. By HD 6, acute kidney injury was evident, with progressive fluid overload >1500 mL (+) for the admission. On HD 6 venoarterial ECLS was instituted for lung protection and fluid removal. On HD 7 she was initiated on CRRT. On HD 12, a blood culture returned positive and subsequently grew Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) for meropenem of 0.25 mg/L. She was started on vancomycin, meropenem, and amikacin. A meropenem bolus of 40 mg/kg was given, followed by a continuous infusion of 10 mg/kg/hr (240 mg/kg/day). On HD 15 (ECLS day 9) a meropenem serum concentration of 21 mcg/mL was obtained, corresponding to a clearance of 7.9 mL/kg/min. Repeat cultures from HDs 13 to 15 (ECLS days 7-9) were sterile. This meropenem regimen was successful in providing a target attainment of 100% for serum concentrations above the MIC for >=40% of the dosing interval and was associated with a sterilization of blood in this complex patient on concurrent ECLS and CRRT circuits. PMID- 26997936 TI - Query Monitoring and Analysis for Database Privacy - A Security Automata Model Approach. AB - Privacy and usage restriction issues are important when valuable data are exchanged or acquired by different organizations. Standard access control mechanisms either restrict or completely grant access to valuable data. On the other hand, data obfuscation limits the overall usability and may result in loss of total value. There are no standard policy enforcement mechanisms for data acquired through mutual and copyright agreements. In practice, many different types of policies can be enforced in protecting data privacy. Hence there is the need for an unified framework that encapsulates multiple suites of policies to protect the data. We present our vision of an architecture named security automata model (SAM) to enforce privacy-preserving policies and usage restrictions. SAM analyzes the input queries and their outputs to enforce various policies, liberating data owners from the burden of monitoring data access. SAM allows administrators to specify various policies and enforces them to monitor queries and control the data access. Our goal is to address the problems of data usage control and protection through privacy policies that can be defined, enforced, and integrated with the existing access control mechanisms using SAM. In this paper, we lay out the theoretical foundation of SAM, which is based on an automata named Mandatory Result Automata. We also discuss the major challenges of implementing SAM in a real-world database environment as well as ideas to meet such challenges. PMID- 26997937 TI - Genetic Basis for Colorectal Cancer Disparities. AB - African Americans suffer the highest burden from colorectal cancer (CRC) in the USA. Studies have suggested that healthcare access and poorer utilization of preventive services may be playing more of a role in this disparity. However, African Americans also tend to develop CRC at younger ages and are more likely to have proximal cancers. This raises the possibility of higher genetic predisposition to CRC among African Americans and this has not been well studied. In this article, we reviewed possible genetic basis underpinning biological differences in CRC burden in the USA. PMID- 26997938 TI - A note on rank reduction in sparse multivariate regression. AB - A reduced-rank regression with sparse singular value decomposition (RSSVD) approach was proposed by Chen et al. for conducting variable selection in a reduced-rank model. To jointly model the multivariate response, the method efficiently constructs a prespecified number of latent variables as some sparse linear combinations of the predictors. Here, we generalize the method to also perform rank reduction, and enable its usage in reduced-rank vector autoregressive (VAR) modeling to perform automatic rank determination and order selection. We show that in the context of stationary time-series data, the generalized approach correctly identifies both the model rank and the sparse dependence structure between the multivariate response and the predictors, with probability one asymptotically. We demonstrate the efficacy of the proposed method by simulations and analyzing a macro-economical multivariate time series using a reduced-rank VAR model. PMID- 26997939 TI - Perceived effectiveness of graphic health warnings as a deterrent for smoking initiation among adolescents in selected schools in southwest Nigeria. AB - BACKGROUND: There has been a sustained increment in young people initiating smoking in low middle income countries like Nigeria. Health warnings on cigarette packages are a prominent source of health information and an effective means of communicating specific disease risks to adolescents and young adults alike. This study evaluated the perceived effectiveness of selected graphic warnings on smoking initiation amongst in-school adolescents. METHODS: This was a cross sectional study conducted amongst secondary school students aged 13-17years in Igbo-Ora, Nigeria. A two-stage sampling technique with the school classes as the final sampling unit was used to select the students. An interviewer assisted questionnaire was used to obtain information on students demographic characteristics and their perception of graphic warnings using four images from the pictorial health warning galleries of the World Health Organization showing: 'cigarette smoking causes cancer of the airways, harms children, causes stroke and causes impotence respectively'. RESULTS: A total of 544 senior secondary students were included in this study with a male female ratio of 0.8:1. Of those interviewed, 40 (7.4 %) indicated that they had ever considered smoking, nine (1.7 %) responded that they had ever smoked and two students indicated that they were current smokers. With all the images, fear was the dominant emotion expressed by the respondents. This was expressed by 307 (56.4), 215 (39.5), 203 (37.3) and 228 (41.9 %) respondents to images 1, 2, 3, and 4 respectively. Furthermore, 76.7, 44.7, 58.5 and 62.1 % of respondents felt Images 1, 2, 3 and 4 respectively will to a large extent prevent people from initiating smoking. There was no association between perceived effectiveness and gender. However, those younger than 15 years rated images on cancer of the airway and impotence as probably effective to a larger extent than did those who were 15 years and older (p = 0.032). CONCLUSION: Introduction of graphic health warnings, especially with an imagery depicting cancer and impotence may influence non-smokers to remain abstinent. Therefore, this study provides a template for a future policy-relevant study on graphic health warning in Nigeria. PMID- 26997940 TI - Chromothripsis after Stumbling through DNA Replication. PMID- 26997942 TI - Clinical and Genetic Heterogeneity of the 15q13.3 Microdeletion Syndrome. AB - The 15q13.3 microdeletion is a recurrent CNV, presumably mediated by NAHR between segmental duplications in chromosome 15. The 15q13.3 deletion and duplication are associated with a wide range of clinical manifestations, such as intellectual deficits, seizures, autism, language and developmental delay, neuropsychiatric impairments, and behavioral problems illustrating incomplete penetrance and expressivity. This study comprises an evaluation of 106 symptomatic patients carrying the heterozygous deletion, as well as of 21 patients carrying the duplication, who have been described in previous studies. The analysis shows considerable heterogeneity for the manifestation of different key symptoms and familiar occurrence. Furthermore, 8 new patients are introduced. Convoluted familiar connections give new insights into the complexity of symptomatic manifestation. In previous studies, different opinions have been expressed as to the nature and precise location of the deletion breakpoints. Here, we show that not CHRNA7 and CHRFAM7A, but rather FAM7A or GOLGA8, serve as breakpoint regions concerning our patients. The deletion is described as heterogeneous in size. However, we assume that not only different breakpoints but also the imprecision of aCGH analysis on chromosome 15 due to segmental duplications accounts for the variability in size. PMID- 26997941 TI - Multiple Small Supernumerary Marker Chromosomes Resulting from Maternal Meiosis I or II Errors. AB - We present 2 cases with multiple de novo supernumerary marker chromosomes (sSMCs), each derived from a different chromosome. In a prenatal case, we found mosaicism for an sSMC(4), sSMC(6), sSMC(9), sSMC(14) and sSMC(22), while a postnatal case had an sSMC(4), sSMC(8) and an sSMC(11). SNP-marker segregation indicated that the sSMC(4) resulted from a maternal meiosis II error in the prenatal case. Segregation of short tandem repeat markers on the sSMC(8) was consistent with a maternal meiosis I error in the postnatal case. In the latter, a boy with developmental/psychomotor delay, autism, hyperactivity, speech delay, and hypotonia, the sSMC(8) was present at the highest frequency in blood. By comparison to other patients with a corresponding duplication, a minimal region of overlap for the phenotype was identified, with CHRNB3 and CHRNA6 as dosage sensitive candidate genes. These genes encode subunits of nicotinic acetylcholine receptors (nAChRs). We propose that overproduction of these subunits leads to perturbed component stoichiometries with dominant negative effects on the function of nAChRs, as was shown by others in vitro. With the limitation that in each case only one sSMC could be studied, our findings demonstrate that different meiotic errors lead to multiple sSMCs. We relate our findings to age-related aneuploidy in female meiosis and propose that predivision sister-chromatid separation during meiosis I or II, or both, may generate multiple sSMCs. PMID- 26997944 TI - Xp22.33p22.12 Duplication in a Patient with Intellectual Disability and Dysmorphic Facial Features. AB - A novel 19.98-Mb duplication in chromosome Xp22.33p22.12 was detected by array CGH in a 30-year-old man affected by intellectual disability, congenital hypotonia and dysmorphic features. The duplication encompasses more than 100 known genes. Many of these genes (such as neuroligin 4, cyclin-dependent kinase like 5, and others) have already correlated with X-linked intellectual disability and/or neurodevelopmental disorders. Due to the high number of potentially pathogenic genes involved in the reported duplication, we cannot correlate the clinical phenotype to a single gene. Indeed, we suggest that the resulting clinical phenotype may have arisen from the overexpression and consequent perturbation of fine gene dosage. PMID- 26997943 TI - Jacobsen Syndrome: Surgical Complications due to Unsuspected Diagnosis, the Importance of Molecular Studies in Patients with Craniosynostosis. AB - Jacobsen syndrome (JBS) is an uncommon contiguous gene syndrome. About 85-92% of cases have a de novo origin. Clinical variability and severity probably depend on the size of the affected region. The typical clinical features in JBS include intellectual disability, growth retardation, craniofacial dysmorphism as well as craniosynostosis, congenital heart disease, and platelet abnormalities. The proband was a 1 year/3-month-old Mexican male. Oligonucleotide-SNP array analysis using the GeneChip Human Cytoscan HD was carried out for the patient from genomic DNA. The SNP array showed a 14.2-Mb deletion in chromosome 11q23.3q25 (120,706 134,938 Mb), which involved 163 RefSeq genes in the database of genomic variation. We report a novel deletion in JBS that increases the knowledge of the variability in the mutation sites in this region and expands the spectrum of molecular and clinical defects in this syndrome. PMID- 26997945 TI - 22q11.2 Deletion Syndrome due to a Translocation t(6;22) in a Patient Conceived via in vitro Fertilization. AB - We report on a patient conceived via in vitro fertilization (IVF) with a 22q11.2 deletion due to an unusual unbalanced translocation involving chromosomes 6 and 22 in a karyotype with 45 chromosomes. Cytogenomic studies showed that the patient has a 3.3-Mb deletion of chromosome 22q and a 0.4-Mb deletion of chromosome 6p, which resulted in haploinsufficiency of the genes responsible for the 22q11.2 deletion syndrome and also of the IRF4 gene, a member of the interferon regulatory factor family of transcription factors, which is expressed in the immune system cells. The rearrangement could be due to the manipulation of the embryo or as a sporadic event unrelated to IVF. Translocation involving chromosome 22 in a karyotype with 45 chromosomes is a rare event, with no previous reports involving chromosomes 6p and 22q. PMID- 26997946 TI - Pre- and Postnatal Analysis of Chromosome 15q26.1 and 8p23.1 Deletions in Congenital Diaphragmatic Hernia. AB - Congenital diaphragmatic hernia (CDH) is defined as a protrusion of abdominal content into the thoracic cavity through an abnormal opening in the diaphragm present at birth. It is a common birth defect with high mortality and morbidity. Submicroscopic deletions of 15q26.1 and 8p23.1 have been reported in several cases of CDH. We studied a total of 17 cases with CDH in pre- and postnatal samples using FISH probes. Deletion 15q26.1 was seen in 1/17 prenatal samples. There was no deletion for 8p23.1 in all the samples analyzed. CDH has a genetic etiology, and deletion 15q26.1 increases the risk of CDH. Deletion 15q26.1 in a fetus with CDH is a predictor of poor prognosis. This deletion is also seen in a phenotype similar to Fryns syndrome. CDH identified pre- or postnatally should be investigated further to exclude a 15q26.1 deletion and enable appropriate parental counseling. PMID- 26997947 TI - A New, Atypical Case of Cobalamin F Disorder Diagnosed by Whole Exome Sequencing. AB - Cobalamin F (cblF) disorder, caused by homozygous or compound heterozygous mutations in the LMBRD1 gene, is a recognised cause of developmental delay, pancytopaenia and failure to thrive which may present in the neonatal period. A handful of cases have been reported in the medical literature. We report a new case, diagnosed at the age of 6 years through whole exome sequencing, with atypical features including prominent metopic suture, cleft palate, unilateral renal agenesis and liver abnormalities, which broaden the phenotypic spectrum. PMID- 26997948 TI - A Rare Case of a Symptomatic Tumor Found in the Groin Area: An Atypical Location Unexposed to the Known Causes. AB - Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The syndrome consists of early onset and/or multiple BCC. Herein we report a rare NBCCS case in which the first BCC onset occurred in the groin area. To the best of our knowledge, there have been no reports of first-onset BCC in the groin area in an NBCCS patient of any race. PMID- 26997950 TI - Pentraxin 3 Is a Predictor for Fibrosis and Arterial Stiffness in Patients with Nonalcoholic Fatty Liver Disease. AB - Objective. The aim of the present study was to investigate whether pentraxin 3 (PTX3) can be a new noninvasive marker for prediction of liver fibrosis in patients with NAFLD. We also aimed to evaluate the relationship between PTX3 and atherosclerosis in patients with NAFLD. Method. Fifty-four male patients with biopsy-proven NAFLD and 20 apparently healthy male volunteers were included. PTX3 levels were determined, using an ELISA method (R&D Sysytems, Quantikine ELISA, USA). To detect the presence of subclinical atherosclerosis in NAFLD, measurements of CIMT, FMD, and cf-PWV levels were performed. Results. PTX3 levels in NAFLD patients with fibrosis were higher than both NAFLD patients without fibrosis and controls (P = 0.032 and P = 0.028, respectively), but there was no difference between controls and NAFLD patients without fibrosis in terms of PTX3 levels (P = 0.903). PTX3 levels were strongly correlated with cf-PWV (r = 0.359, P = 0.003), whereas no significant correlation was found with other atherosclerosis markers, CIMT and FMD. Conclusion. Elevated plasma PTX3 levels are associated with the presence of fibrosis in patients with NAFLD, independently of metabolic syndrome components. This study demonstrated that for the first time there is a close association between elevated PTX3 levels and increased arterial stiffness in patients with NAFLD. PMID- 26997949 TI - Higher Levels of Cystatin C Are Associated with Extracranial Carotid Artery Steno Occlusive Disease in Patients with Noncardioembolic Ischemic Stroke. AB - BACKGROUND: Large artery atherosclerosis is a major cause of ischemic stroke worldwide. Differential biomarker profiles associated with extra- and intracranial atherosclerosis are a topic of considerable interest. Cystatin C (CysC), a marker of renal function, is a risk factor for cardiovascular disease. AIM: We sought to determine whether CysC levels were associated with extra- and intracranial large artery stenosis (LAS) in patients with acute ischemic stroke. METHODS: We retrospectively analyzed data of acute noncardioembolic ischemic stroke patients who were admitted to our stroke center within 5 days from symptom onset. Serum CysC levels were measured using latex agglutination turbidimetric immunoassay. Extra- and intracranial LAS were defined as >= 50% diameter stenosis or occlusion of the relevant internal carotid artery (ICA) and/or middle cerebral artery (MCA) using carotid echography and volume rendering on magnetic resonance angiography. Multivariate logistic analyses were used to assess the association between CysC levels and LAS after adjustment for potential confounders. RESULTS: Of 205 patients (mean age 70.2 years), 76 (37.1%) had LAS. The distribution of LAS was 29 extracranial ICA, 34 intracranial ICA/MCA (8 ICA only, 25 MCA only, 1 ICA+MCA) and 13 tandem stenosis (both extracranial ICA and intracranial ICA/MCA). Levels of CysC were higher in patients with extracranial ICA stenosis than in those with intracranial ICA/MCA stenosis (1.23 +/- 0.33 vs. 0.97 +/- 0.21 mg/l, p < 0.001). In multivariate analysis, the highest CysC tertile (>1.04 mg/l) was significantly associated with extracranial ICA stenosis (adjusted odds ratio [OR] 5.01, 95% confidence interval [CI] 1.51-16.63, p = 0.009) after adjustment for age, sex, diabetes, chronic kidney disease, current smoking, systolic blood pressure, HDL cholesterol, high-sensitivity C-reactive protein (hs-CRP) and premorbid lipid-lowering drugs use. When CysC was considered as a continuous variable, 1 SD increase in CysC was significantly associated with extracranial ICA stenosis (adjusted OR 3.01, 95% CI 1.58-5.72, p = 0.001). However, there were no significant associations between CysC levels and intracranial ICA/MCA stenosis. In addition, CysC levels showed a weak but statistically significant correlation with hs-CRP levels (r = 0.195, p = 0.021). Using receiver operating characteristic curve analysis, CysC value displayed good performance in discriminating extracranial ICA stenosis (c-statistic 0.79, 95% CI 0.69-0.89, p < 0.001). CONCLUSIONS: This preliminary study suggests that higher levels of CysC were independently associated with symptomatic extracranial ICA stenosis, but not with intracranial ICA/MCA stenosis in patients with noncardioembolic stroke. Our findings provide new insights into the link between serum CysC and carotid atherosclerosis. PMID- 26997951 TI - Comparison of Nasopharyngeal Airway Device and Nasal Oxygen Tube in Obese Patients Undergoing Intravenous Anesthesia for Gastroscopy: A Prospective and Randomized Study. AB - Objective. This prospective and randomized study evaluated the efficacy and safety of the nasopharyngeal airway relative to the nasal oxygen tube in obese patients undergoing painless gastroscopy. Materials and Methods. Obese patients (BMI >= 28 kg/m(2); n = 260) were randomly and equally apportioned to the nasopharyngeal airway (Group A) or nasal oxygen tube (Group B) group. Three patients were excluded due to failure of insertion of the nasopharyngeal airway. The duration of endoscopy, anesthetic dose, recovery time, and adverse events were recorded. The satisfaction of the anesthetist, physicians, and patient was scored. Results. The SpO2 reduction was significantly less in Group A than in Group B. Use of a respirator for assisted ventilation occurred significantly less in Group A. The groups were similar regarding mean arterial pressure, heart rate, anesthetic dose, duration of gastroscopy, recovery time, and adverse events. Satisfaction of the physician and anesthetist was greater in Group A; the groups were similar in patient satisfaction. Conclusions. Use of the nasopharyngeal airway for obese patients during painless gastroscopy resulted in less SpO2 reduction relative to the nasal oxygen tube. Altogether, it is a safe and effective device for obese patients undergoing painless gastroscopy. PMID- 26997952 TI - Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn's Disease. AB - Background. Assessment of endoscopic activity of Crohn's disease (CD) is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn's Disease (SES-CD). PMID- 26997954 TI - Cumulative Impact of HIV and Multiple Concurrent Human Papillomavirus Infections on the Risk of Cervical Dysplasia. AB - Infection with HIV is known to increase the risk of cervical cancer. In addition, evidence suggests that concurrent infection with multiple human papillomavirus (HPV) genotypes increases the risk of cervical dysplasia more than infection with a single HPV genotype. However, the impact of the combination of HIV coinfection and presence of multiple concurrent HPV infections on the risk of cervical dysplasia is uncertain. We compared the results of HPV testing and Pap smears between HIV-infected and HIV-uninfected young women to assess the cumulative impact of these two conditions. We found that both HIV and the presence of multiple concurrent HPV infections are associated with increased risk of associated Pap smear abnormality and that the impact of these two risk factors may be additive. PMID- 26997953 TI - Potential Effects of Silymarin and Its Flavonolignan Components in Patients with beta-Thalassemia Major: A Comprehensive Review in 2015. AB - Major beta-thalassemia (beta-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of beta-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with beta-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions. PMID- 26997956 TI - Penicillin G-Induced Chlamydial Stress Response in a Porcine Strain of Chlamydia pecorum. AB - Chlamydia pecorum causes asymptomatic infection and pathology in ruminants, pigs, and koalas. We characterized the antichlamydial effect of the beta lactam penicillin G on Chlamydia pecorum strain 1710S (porcine abortion isolate). Penicillin-exposed and mock-exposed infected host cells showed equivalent inclusions numbers. Penicillin-exposed inclusions contained aberrant bacterial forms and exhibited reduced infectivity, while mock-exposed inclusions contained normal bacterial forms and exhibited robust infectivity. Infectious bacteria production increased upon discontinuation of penicillin exposure, compared to continued exposure. Chlamydia-induced cell death occurred in mock-exposed controls; cell survival was improved in penicillin-exposed infected groups. Similar results were obtained both in the presence and in the absence of the eukaryotic protein translation inhibitor cycloheximide and at different times of initiation of penicillin exposure. These data demonstrate that penicillin G induces the chlamydial stress response (persistence) and is not bactericidal, for this chlamydial species/strain in vitro, regardless of host cell de novo protein synthesis. PMID- 26997955 TI - Characterization of IXINITY(r) (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph. AB - The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed <0.002 IU of activated factor IX (FIXa) per IU of FIX. The molecule has >97% gamma-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX. PMID- 26997957 TI - Intraperitoneal Injection of Multiplacentas Pooled Cells Treatment on a Mouse Model with Aplastic Anemia. AB - Coinfusion of hematopoietic and mesenchymal stem cells is more effective than hematopoietic stem cell transplantation alone. It is necessary to explore a safe and routine mixed stem cell intraperitoneal transplantation method. Multiplacentas pooled cells were intraperitoneally injected into a radiation- and immunity-induced mouse aplastic anemia model with single time. Then, mouse survival time, peripheral blood hemoglobin count, bone marrow architecture, and donor cell engraftment were assessed. The recipient mouse exhibited donor cell engraftment in both bone marrow and peripheral blood. Survival time and peripheral blood hemoglobin count increased in placenta pooled cells treated mice, compared with model-only controls (P = 0.048 and P = 0.000, resp.). However, placentas pooled cells failed to cause a significant decrease in bone marrow pimelosis area (P = 0.357). Intraperitoneally transplanted multiplacentas pooled cells can survive and engraft into a host body through blood circulation, which can increase the life span of an aplastic anemia model mice, and delay but not abrogate the development of aplastic anemia. Furthermore, they appear to play a role in increasing peripheral blood hemoglobin level response for increasing the life span of aplastic anemia model mice. PMID- 26997962 TI - Liuwei Dihuang Pills Enhance the Effect of Western Medicine in Treating Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials. AB - Objectives. To assess the effectiveness and adverse effects of adding Liuwei Dihuang Pills (LDP) to Western medicine for treating diabetic nephropathy. Methods. Studies were retrieved from seven electronic databases, including PubMed, Embase, The Cochrane Library, CBM, CNKI, Chinese Scientific Journal Database (VIP), and Wanfang Data until November 2015. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. Meta-analysis was performed on the overall therapeutic efficacy of hyperglycemia and renal functions, and the study also analyzed adverse events. Results. A total of 1,275 patients from 18 studies were included. The methodological quality of these included trials was generally low. We found that adding LDP can lower patients' FBG (MD: -0.36 [-0.46, -0.25], P < 0.00001), PBG (MD: -1.10 [-1.35, -0.85], P < 0.00001), and HbA1c (MD: -0.14 [-0.49, 0.21], P = 0.43). There were also improvements in lowering patients' BUN (MD: -0.67 [ 0.89, -0.45], P < 0.00001), SCr (MD: -0.96 [-1.53, -0.39], P < 0.00001), 24 h UTP (SMD: -1.26 [-2.38, -0.15], P < 0.00001), UAER (MD: -26.18 [-27.51, -24.85], P < 0.00001), and UmAlb (SMD: -1.72 [-2.67, -0.77], P < 0.00001). Conclusion. There is encouraging evidence that adding LDP to Western medicine might improve treatment outcomes of diabetic nephropathy, including hyperglycemia and renal functions. However, the evidence remains weak. More rigorous high-quality trials are warranted to substantiate or refute the results. PMID- 26997960 TI - A Simple Allergist-Led Intervention Improves Resident Training in Anaphylaxis. AB - Physicians underrecognize and undertreat anaphylaxis. Effective interventions are needed to improve physician knowledge and competency regarding evidence-based anaphylaxis diagnosis and management (ADAM). We designed and evaluated an educational program to improve ADAM in pediatrics, internal medicine, and emergency medicine residents from two academic medical centers. Anonymous questionnaires queried participants' demographics, prior ADAM clinical experience, competency, and comfort. A pretest assessing baseline knowledge preceded a 45-minute allergist-led evidence-based presentation, including practice with epinephrine autoinjectors, immediately followed by a posttest. A follow-up test assessed long-term knowledge retention twelve weeks later. 159 residents participated in the pretest, 152 participated in the posttest, and 86 participated in the follow-up test. There were no significant differences by specialty or site. With a possible score of 10, the mean pretest score (7.31 +/- 1.50) was lower than the posttest score (8.79 +/- 1.29) and follow-up score (8.17 +/- 1.72) (P < 0.001 for both). Although participants' perceived confidence in diagnosing or managing anaphylaxis improved from baseline to follow-up (P < 0.001 for both), participants' self-reported clinical experience with ADAM or autoinjector use was unchanged. Allergist-led face-to-face educational intervention improves residents' short-term knowledge and perceived confidence in ADAM. Limited clinical experience or reinforcement contributes to the observed decreased knowledge. PMID- 26997959 TI - Stem Cells for Bone Regeneration: From Cell-Based Therapies to Decellularised Engineered Extracellular Matrices. AB - Currently, autologous bone grafting represents the clinical gold standard in orthopaedic surgery. In certain cases, however, alternative techniques are required. The clinical utility of stem and stromal cells has been demonstrated for the repair and regeneration of craniomaxillofacial and long bone defects although clinical adoption of bone tissue engineering protocols has been very limited. Initial tissue engineering studies focused on the bone marrow as a source of cells for bone regeneration, and while a number of promising results continue to emerge, limitations to this technique have prompted the exploration of alternative cell sources, including adipose and muscle tissue. In this review paper we discuss the advantages and disadvantages of cell sources with a focus on adipose tissue and the bone marrow. Additionally, we highlight the relatively recent paradigm of developmental engineering, which promotes the recapitulation of naturally occurring developmental processes to allow the implant to optimally respond to endogenous cues. Finally we examine efforts to apply lessons from studies into different cell sources and developmental approaches to stimulate bone growth by use of decellularised hypertrophic cartilage templates. PMID- 26997963 TI - Electroacupuncture at ST25 Inhibits Cisapride-Induced Gastric Motility in an Intensity-Dependent Manner. AB - Background. Previous studies have demonstrated the efficacy of frequency-specific EAS. However, evaluation of intensity-response effects is challenging and has yet to be addressed. Aims. Using cisapride to promote gastric emptying, we measured the intensity-response relationship of EA at ST25 on gastric motility. Methods. We determined the effects of EA at ST25 using intensities (0.5, 1, 3, 5, 7, and 9 mA) on gastric motility in rats injected with cisapride (0.2, 0.02, and 0.002 mg/kg). Results. Utilizing three concentrations of cisapride yielded significantly differing levels of gastric motility. Furthermore, log IC50 values for EAS were different within each group. Given the same EA intensity, cisapride antagonism decreased progressively in each group as a function of drug concentration. The relative amount of cisapride antagonized by EAS did not change in a linear fashion. Finally, EAS at different intensities within the three groups induced a similar pattern of cisapride antagonism. Conclusions. The ability of EAS to elicit a decrease in cisapride-induced gastric motility pressure was demonstrated in this study. The study encompasses construct validity to mirror individualized treatment being based on patients' subjective feelings, not on a set fixed EA intensity. Clinically utilizing EAS at the smallest intensity can achieve the desired therapeutic effect. PMID- 26997958 TI - Increased Understanding of Stem Cell Behavior in Neurodegenerative and Neuromuscular Disorders by Use of Noninvasive Cell Imaging. AB - Numerous neurodegenerative and neuromuscular disorders are associated with cell specific depletion in the human body. This imbalance in tissue homeostasis is in healthy individuals repaired by the presence of endogenous stem cells that can replace the lost cell type. However, in most disorders, a genetic origin or limited presence or exhaustion of stem cells impairs correct cell replacement. During the last 30 years, methods to readily isolate and expand stem cells have been developed and this resulted in a major change in the regenerative medicine field as it generates sufficient amount of cells for human transplantation applications. Furthermore, stem cells have been shown to release cytokines with beneficial effects for several diseases. At present however, clinical stem cell transplantations studies are struggling to demonstrate clinical efficacy despite promising preclinical results. Therefore, to allow stem cell therapy to achieve its full potential, more insight in their in vivo behavior has to be achieved. Different methods to noninvasively monitor these cells have been developed and are discussed. In some cases, stem cell monitoring even reached the clinical setting. We anticipate that by further exploring these imaging possibilities and unraveling their in vivo behavior further improvement in stem cell transplantations will be achieved. PMID- 26997964 TI - TLR-6 SNP P249S is associated with healthy aging in nonsmoking Eastern European Caucasians - A cohort study. AB - BACKGROUND: To investigate mechanisms that determine healthy aging is of major interest in the modern world marked by longer life expectancies. In addition to lifestyle and environmental factors genetic factors also play an important role in aging phenotypes. The aged immune system is characterized by a chronic micro inflammation, known as inflamm-aging, that is suspected to trigger the onset of age-related diseases such as cardiovascular disease, Alzheimer's disease, cancer, and Diabetes Mellitus Type 2 (DMT2). We have recently shown that a Toll-like receptor 6 variant (P249S) is associated with susceptibility to cardiovascular disease and speculated that this variant may also be associated with healthy aging in general by decreasing the process of inflamm-aging. RESULTS: Analyzing the PolSenior cohort we show here that nonsmoking S allele carriers are significantly protected from age-related diseases (P = 0.008, OR: 0.654). This association depends not only on the association with cardiovascular diseases (P = 0.018, OR: 0.483) for homozygous S allele carriers, but is also driven by a protection from Diabetes Mellitus type 2 (P = 0.010, OR: 0.486) for S allele carriers. In addition we detect a trend but no significant association of this allele with inflamm-aging in terms of baseline IL-6 levels. CONCLUSION: We confirm our previous finding of the TLR-6 249S variant to be protective regarding cardiovascular diseases. Furthermore, we present first evidence of TLR-6 249S being involved in DMT2 susceptibility and may be in general associated with healthy aging possibly by reducing the process of inflamm-aging. PMID- 26997966 TI - Methods of nutrition surveillance in low-income countries. AB - BACKGROUND: In 1974 a joint FAO/UNICEF/WHO Expert Committee met to develop methods for nutrition surveillance. There has been much interest and activity in this topic since then, however there is a lack of guidance for practitioners and confusion exists around the terminology of nutrition surveillance. In this paper we propose a classification of data collection activities, consider the technical issues for each category, and examine the potential applications and challenges related to information and communication technology. ANALYSIS: There are three major approaches used to collect primary data for nutrition surveillance: repeated cross-sectional surveys; community-based sentinel monitoring; and the collection of data in schools. There are three major sources of secondary data for surveillance: from feeding centres, health facilities, and community-based data collection, including mass screening for malnutrition in children. Surveillance systems involving repeated surveys are suitable for monitoring and comparing national trends and for planning and policy development. To plan at a local level, surveys at district level or in programme implementation areas are ideal, but given the usually high cost of primary data collection, data obtained from health systems are more appropriate provided they are interpreted with caution and with contextual information. For early warning, data from health systems and sentinel site assessments may be valuable, if consistent in their methods of collection and any systematic bias is deemed to be steady. For evaluation purposes, surveillance systems can only give plausible evidence of whether a programme is effective. However the implementation of programmes can be monitored as long as data are collected on process indicators such as access to, and use of, services. Surveillance systems also have an important role to provide information that can be used for advocacy and for promoting accountability for actions or lack of actions, including service delivery. CONCLUSION: This paper identifies issues that affect the collection of nutrition surveillance data, and proposes definitions of terms to differentiate between diverse sources of data of variable accuracy and validity. Increased interest in nutrition globally has resulted in high level commitments to reduce and prevent undernutrition. This review helps to address the need for accurate and regular data to convert these commitments into practice. PMID- 26997967 TI - Using soccer to build confidence and increase HCT uptake among adolescent girls: A mixed-methods study of an HIV prevention programme in South Africa. AB - HIV prevalence is eight times higher in young South African women compared to men. Grassroot Soccer (GRS) developed SKILLZ Street (SS), a single-sex intervention using soccer to improve self-efficacy, HIV-related knowledge, and HIV counselling and testing (HCT) uptake among girls ages 12-16. Female community leaders-"coaches"-deliver ten 2-hour sessions bi-weekly. Attendance and HCT data were collected at 38 programmes across 5 GRS sites during 24 months in 2011-2012. 514 participants completed a 16-item pre/post questionnaire. Focus group discussions (FGDs) were conducted with participants (n=11 groups) and coaches (n=5 groups), and coded for analysis using NVivo. Of 1,953 participants offered HCT, 68.5% tested. Overall, significant pre/post improvement was observed (p<0.001). FGDs suggest participants: valued coach-participant relationship; improved self-efficacy, HIV-related knowledge, communication, and changed perception of soccer as a male-only sport; and increased awareness of testing's importance. Results suggest SS helps at-risk girls access HCT and HIV-related knowledge while promoting self-confidence. PMID- 26997968 TI - Evaluation of markers of beige adipocytes in white adipose tissue of the mouse. AB - BACKGROUND: There is a growing interest in exploiting the induction of beige or "brite" (brown in white) adipocytes (beigeing) to combat obesity and its comorbidities. However, there is some uncertainty regarding the best markers to evaluate the occurrence or magnitude of beigeing in white adipose tissue in the mouse model. METHODS: We evaluated the transcript expression of several thermoregulatory genes and proposed beige markers employing cell culture, whole white adipose tissue, and the adipocyte and stromal vascular fractions. RESULTS: Most beige markers tested with the exception of TMEM26 can discriminate white from beige adipocytes in culture. Markers FGF21, P2RX5, PAT2, or CAR4 can successfully mark beigeing in whole tissue of younger mice, or in the adipocyte subfraction of older mice. However, markers for the thermoregulatory genes UCP1, CIDEA, and Cox8b displayed the greatest dynamic range and were consistently elevated in vitro, in vivo, and in the adipocyte fraction by treatments that induce beige adipogenesis. CONCLUSIONS: While most putative beige markers are clearly expressed in beige adipocytes in vitro, in vivo the small dynamic range of most of these markers, the strength of the beigeing stimulus, and the age of the mice may limit their utility, although this limitation may be overcome by specifically evaluating these markers in the adipocyte fraction. Thermoregulatory markers like UCP1, CIDEA, or Cox8b represent the best options to evaluate the beigeing of white adipose tissue in vivo. PMID- 26997965 TI - The role of NK cells in HIV-1 protection: autologous, allogeneic or both? AB - Natural killer (NK) cells specialize in killing virally infected- or tumor cells and are part of the innate immune system. The activational state of NK cells is determined by the balance of incoming activating and inhibitory signals mediated by receptor-ligand binding with the target cell. These receptor-ligand bonds mainly consist of the killer immunoglobulin-like receptors (KIR), which are expressed at the cell surface of NK cells, and their ligands: the highly variable human leukocyte antigen -class I molecules (HLA). Absence of an inhibitory receptor-ligand bond lowers the NK cell activation threshold, whereas an activating receptor-ligand bond stimulates the cell, potentially overcoming this threshold and triggering NK cell activation. NK cells influence the course of infection as well as the acquisition of HIV-1. Several lines of evidence relate the activating NK cell receptor KIR3DS1, in the presence or absence of its putative ligand HLA-Bw4, with slower disease progression as well as resistance to HIV-1 infection. Overall, resistance to HIV-1 infection predominantly correlates with activating KIR/HLA profiles, consisting of e.g. activating KIRs, group B haplotypes, or inhibitory KIRs in absence of their ligands. Such a conclusion is less evident for studies of HIV-1 disease progression, with studies reporting beneficial as well as detrimental effects of activating KIR/HLA genotypes. It is likely that KIR/HLA association studies are complicated by the complexity of the KIR and HLA loci and their mutual interactions, as well as by additional factors like route of HIV exposure, immune activation, presence of co-infections, and the effect of anti-HIV-1 antibodies. One newly discovered NK cell activation pathway associated with resistance to HIV-1 infection involves the presence of an iKIR/HLA mismatch between partners. The absence of such an iKIR/HLA bond renders donor-derived allogeneic HIV-1 infected cells vulnerable to NK cell responses during HIV-1 transmission. Therefore, theoretically, HIV-1 would be eliminated before it has the chance to infect the autologous cells in the recipient. While this "alloreactive" NK cell mechanism is especially relevant to HIV transmission in monogamous couples, it would be interesting to investigate how it could influence resistance to HIV in other settings. The objective of this review is to summarize the knowledge about these autologous and alloreactive NK cell responses with regard to HIV-1 outcome. PMID- 26997969 TI - A Longitudinal Investigation of Relational Catalyst Support of Goal Strivings. AB - The goal of this work was to test a theoretical model of relational catalyst support provision that promotes thriving in non-adverse times. We tested a pathway proposed by Feeney and Collins (2014) that explains how relational catalyst support in the context of close relationships might lead to thriving. We proposed that once relational catalyst support has been received, it functions through the mechanisms of being perceived to be responsive to one's needs and promoting perceived capability. Perceived capability should promote indices of thriving including self-esteem, goal accomplishment, growth, and specific and general availability of support. This model was supported in two studies of married couples using observational and longitudinal methods surrounding the support of goal-strivings. Results indicate that (a) partner support of goal strivings predicted important indicators of thriving over time, and (b) both received and perceived relational catalyst support work together and play important roles in predicting these outcomes. PMID- 26997970 TI - Fipronil induces lung inflammation in vivo and cell death in vitro. AB - BACKGROUND: Fipronil is an insecticide that acts at the gamma-aminobutyric acid receptor and glutamate-gated chloride channels in the central nervous systems of target organisms. The use of fipronil is increasing across the globe. Presently, very little data exist on the potential impact of exposure to fipronil on the lungs. METHODS: We studied effects of intranasal (N = 8) and oral (N = 8) treatment with fipronil (10 mg/kg) on lungs of mice. Control mice were given groundnut oil orally (N = 7) or ethanol intranasally (N = 7) as these were the vehicles for respective treatments. RESULTS: Hematoxylin-eosin stained lung sections showed normal histology in the control lungs compared to the thickened alveolar septa, disruption of the airways epithelium and damage to vascular endothelium in the intranasal and the oral groups. Mice exposed to fipronil either orally or intranasally showed increased von Willebrand factor staining in the endothelium and septal capillaries. Compared to the control mice, TLR4 expression in airway epithelium was increased in mice treated intranasally but not orally with fipronil. Oral fipronil reduced TLR9 staining in the airway epithelium but intranasal exposure caused intense staining in the alveolar septa and airway epithelium. There were higher numbers of TLR4 positive cells in alveolar septa in lungs of mice treated intranasally (P = 0.010) compared to the respective control and orally treated mice but no significant differences between treatments for TLR9 positive stained cells (P = 0.226). The U937 macrophage cells exposed to fipronil at concentrations of 0.29 MUm to 5.72 MUm/ml over 3- or 24 hour showed significant increase in cell death at higher concentrations of fipronil (P < 0.0001). Western blots revealed no effect of fipronil on TLR4 (P = 0.49) or TLR9 (P = 0.94) expression on macrophage cell line. CONCLUSION: While both oral or intranasal fipronil treatments induced signs of lung inflammation, the number TLR4-positive septal cells was increased only following intranasal treatment. Fipronil causes macrophage cell death without altering TLR4 and TLR9 expression in vitro. PMID- 26997971 TI - Factors associated with exclusive breastfeeding practices among mothers in dubti town, afar regional state, northeast Ethiopia: a community based cross-sectional study. AB - BACKGROUND: Exclusive breastfeeding for the first 6 months of life is recommended internationally. This study aimed to investigate exclusive breastfeeding practices and associated factors among mothers of infants aged less than 6 months. METHODS: A community based cross-sectional study was conducted on mother infant pairs in Dubti town in May, 2015. In this study, exclusive breastfeeding was defined as an infant's breast milk consumption without supplementation of any type of food or drink, except for vitamins, minerals and necessary medications in the 24 h preceding the survey. Descriptive statistics, bivariate and multivariable logistic regression analysis were employed to identify the factors associated with exclusive breastfeeding practices. Variables with a p-value < 0.05 in the multivariable model were identified as predictors of exclusive breastfeeding practices. RESULTS: Exclusive breastfeeding under 6 months was practiced by 81.1 % (95 % Confidence Interval [CI] 77.0, 85.0 %) of mothers of infants aged less than 6 months. The median duration of exclusive breastfeeding for infants less than 6 months was 3 months. Multivariable logistic regression analysis showed that initiation of breastfeeding within 1 h after birth (Adjusted Odds Ratio [AOR] 5.46; 95 % CI 1.93, 15.41), age of infants of less than 2 months (AOR 7.03; 95 % CI 2.16, 22.88), being a housewife (AOR 4.81; 95 % CI 2.30, 10.06) and mothers who received postnatal counseling (AOR 3.88; 95 % CI 1.88, 7.99) were positive predictors of exclusive breastfeeding. CONCLUSION: The study revealed that exclusive breastfeeding under 6 months using 24-h recall method was lower than the World Health Organization recommendation. Therefore, interventions could focus on educating mothers the importance of timely initiation of breastfeeding and postnatal care in the study area. PMID- 26997972 TI - Mathematical Modelling and Analysis of the Tumor Treatment Regimens with Pulsed Immunotherapy and Chemotherapy. AB - To begin with, in this paper, single immunotherapy, single chemotherapy, and mixed treatment are discussed, and sufficient conditions under which tumor cells will be eliminated ultimately are obtained. We analyze the impacts of the least effective concentration and the half-life of the drug on therapeutic results and then find that increasing the least effective concentration or extending the half life of the drug can achieve better therapeutic effects. In addition, since most types of tumors are resistant to common chemotherapy drugs, we consider the impact of drug resistance on therapeutic results and propose a new mathematical model to explain the cause of the chemotherapeutic failure using single drug. Based on this, in the end, we explore the therapeutic effects of two-drug combination chemotherapy, as well as mixed immunotherapy with combination chemotherapy. Numerical simulations indicate that combination chemotherapy is very effective in controlling tumor growth. In comparison, mixed immunotherapy with combination chemotherapy can achieve a better treatment effect. PMID- 26997973 TI - A new method for estimating carbon dioxide emissions from transportation at fine spatial scales. AB - Detailed estimates of carbon dioxide (CO2) emissions at fine spatial scales are useful to both modelers and decision makers who are faced with the problem of global warming and climate change. Globally, transport related emissions of carbon dioxide are growing. This letter presents a new method based on the volume preserving principle in the areal interpolation literature to disaggregate transportation-related CO2 emission estimates from the county-level scale to a 1 km2 grid scale. The proposed volume-preserving interpolation (VPI) method, together with the distance-decay principle, were used to derive emission weights for each grid based on its proximity to highways, roads, railroads, waterways, and airports. The total CO2 emission value summed from the grids within a county is made to be equal to the original county-level estimate, thus enforcing the volume-preserving property. The method was applied to downscale the transportation-related CO2 emission values by county (i.e. parish) for the state of Louisiana into 1 km2 grids. The results reveal a more realistic spatial pattern of CO2 emission from transportation, which can be used to identify the emission 'hot spots'. Of the four highest transportation-related CO2 emission hotspots in Louisiana, high-emission grids literally covered the entire East Baton Rouge Parish and Orleans Parish, whereas CO2 emission in Jefferson Parish (New Orleans suburb) and Caddo Parish (city of Shreveport) were more unevenly distributed. We argue that the new method is sound in principle, flexible in practice, and the resultant estimates are more accurate than previous gridding approaches. PMID- 26997974 TI - Proteomic analysis of the biomass hydrolytic potentials of Penicillium oxalicum lignocellulolytic enzyme system. AB - BACKGROUND: The mining of high-performance enzyme systems is necessary to develop industrial lignocellulose bioconversion. Large amounts of cellulases and hemicellulases can be produced by Penicillium oxalicum. Hence, the enzyme system of this hypercellulolytic fungus should be elucidated to help design optimum enzyme systems for effective biomass hydrolysis. RESULTS: The cellulolytic and xylanolytic activities of an SP enzyme system prepared from P. oxalicum JU-A10 were comparatively analyzed. Results indicated that the fungus possesses a complete cellulolytic-xylanolytic enzyme system. The cellobiohydrolase- and xylanase-specific activities of this system were higher than those of two other enzyme systems, i.e., ST from Trichoderma reesei SN1 and another commercial preparation Celluclast 1.5L. Delignified corncob residue (DCCR) could be hydrolyzed by SP to a greater extent than corncob residue (CCR). Beta-glucosidase (BG) supplemented in SP increased the ability of the system to hydrolyze DCCR and CCR, and resulted in a 64 % decrease in enzyme dosage with the same glucose yield. The behaviors of the enzyme components in the hydrolysis of CCR were further investigated by monitoring individual enzyme dynamics. The total protein concentrations and cellobiohydrolase (CBH), endoglucanase (EG), and filter paper activities in the supernatants significantly decreased during saccharification. These findings were more evident in SP than in the other enzyme systems. The comparative proteomic analysis of the enzyme systems revealed that both SP and ST were rich in carbohydrate-degrading enzymes and multiple non-hydrolytic proteins. A larger number of carbohydrate-binding modules 1 (CBM1) were also identified in SP than in ST. This difference might be linked to the greater adsorption to substrates and lower hydrolysis efficiency of SP enzymes than ST during lignocellulose saccharification, because CBM1 not only targets enzymes to insoluble cellulose but also leads to non-productive adsorption to lignin. CONCLUSIONS: Penicillium oxalicum can be applied to the biorefinery of lignocellulosic biomass. Its ability to degrade lignocellulosic substrates could be further improved by modifying its enzyme system on the basis of enzyme activity measurement and proteomic analysis. The proposed strategy may also be applied to other lignocellulolytic enzyme systems to enhance their hydrolytic performances rationally. PMID- 26997975 TI - Systematic engineering of the central metabolism in Escherichia coli for effective production of n-butanol. AB - BACKGROUND: Microbes have been extensively explored for production of environment friendly fuels and chemicals. The microbial fermentation pathways leading to these commodities usually involve many redox reactions. This makes the fermentative production of highly reduced products challenging, because there is a limited NADH output from glucose catabolism. Microbial production of n-butanol apparently represents one typical example. RESULTS: In this study, we addressed the issue by adjustment of the intracellular redox state in Escherichia coli. This was initiated with strain BuT-8 which carries the clostridial CoA-dependent synthetic pathway. Three metabolite nodes in the central metabolism of the strain were targeted for engineering. First, the pyruvate node was manipulated by enhancement of pyruvate decarboxylation in the oxidative pathway. Subsequently, the pentose phosphate (PP) pathway was amplified at the glucose-6-phosphate (G6P) node. The pathway for G6P isomerization was further blocked to force the glycolytic flux through the PP pathway. It resulted in a growth defect, and the cell growth was later recovered by limiting the tricarboxylic acid cycle at the acetyl-CoA node. Finally, the resulting strain exhibited a high NADH level and enabled production of 6.1 g/L n-butanol with a yield of 0.31 g/g-glucose and a productivity of 0.21 g/L/h. CONCLUSIONS: The production efficiency of fermentative products in microbes strongly depends on the intracellular redox state. This work illustrates the flexibility of pyruvate, G6P, and acetyl-CoA nodes at the junction of the central metabolism for engineering. In principle, high production of reduced products of interest can be achieved by individual or coordinated modulation of these metabolite nodes. PMID- 26997976 TI - Assessing clarity and erasability of commercially available pens for surgical site marking: a comparative study in human volunteers. AB - BACKGROUND: Marking the surgical site is a well-established part of pre-operative protocol and errors in marking have been implicated in wrong site surgery incidents and are a significant patient safety issue. There are many commercially available marker pens and anecdotally very little consistency in which pen is used or the clarity of marking. Previous studies have shown subjective differences between different pens and the current paper sought to support this evidence with objective data and widen the investigation of commercially available pens. METHODS: Eight marker pens were used to mark two separate sites on three caucasian volunteers. These marks were photographed and assessed by six observers before and after the application of chlorhexidine skin preparation. The observers were blinded to which pen was used for each mark, and rated the clarity of the marks subjectively. The photographs were assessed using image analysis software to give an objective measure of clarity against the skin. RESULTS: There was a wide variation between the clarity of marks made by the different pens, and also a wide variation in the resistance to skin preparation. The Pentel N50 pen was the outstanding best performing pen across all categories. CONCLUSIONS: It is recommended that the Pentel N50 black marker pen be used for surgical site marking to improve patient safety and avoid adverse events. PMID- 26997977 TI - Comparative deletion mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability. AB - BACKGROUND: While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microdeletions in the short arm have been documented. More than half of the 1p microdeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microdeletions have not been clearly defined. RESULTS: We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microdeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA. Comparative deletion mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes (DAB1, HOOK1, NFIA, DOCK7, DNAJC6, and PDE4B) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microdeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. CONCLUSION: We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microdeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability. PMID- 26997980 TI - Characterization of Polyamidoamino (PAMAM) Dendrimers Using In-Line Reversed Phase LC Electrospray Ionization Mass Spectrometry. AB - Generation 3 (G3) PAMAM dendrimers are symmetrical, highly branched polymers widely reported in the scientific literature as therapeutic agents themselves or as carrier scaffolds for various therapeutic agents. A large number of analytical techniques have been applied to study PAMAM dendrimers, but one that has been missing is in-line reversed phase LC electrospray ionization mass spectrometry (RP/LC/ESI/MS). To translate PAMAM dendrimers into therapeutic agents, a better understanding of their purity, stability and structure is required, and in-line RP/LC/ESI/MS is widely applied to all three of these analytical questions. In this study, we developed a robust in-line RP/LC/ESI/MS method for assessing stability, purity and structure of the G3 PAMAM dendrimers, and we also examined the reasons why previous attempts at method development failed. Using the RP/LC/ESI/MS method we uncovered several unique aspects of the chemistry of G3 PAMAM dendrimers. They are interconverted between two isomeric forms by dialysis, and under higher concentration levels there is an inter-molecular displacement reaction resulting, which degrades PAMAM dendrimers. Purification of G3 dendrimers by RP/LC was also previously unreported; so we slightly modified the LC/MS method for isolating individual components from a complex dendrimer mixture. Thus, we have developed a robust, comprehensive method for characterizing PAMAM dendrimers and their degradation. PMID- 26997979 TI - Oxidative stress due to Mycobacterium avium subspecies paratuberculosis (MAP) infection upregulates selenium-dependent GPx activity. AB - OBJECTIVE: This study was designed to determine the relationship between Mycobacterium avium subspecies paratuberculosis (MAP) infection and selenium dependent glutathione peroxidase (GPx) activity, in the blood of humans and cattle infected with MAP. DESIGN: MAP infection status and GPx activity were determined in sera from 42 cattle, a group of 27 patients with Crohn's disease and 27 of their healthy biological relatives, and a group of 66 subjects with various diseases other than Crohn's disease and 34 non-related healthy subjects. RESULTS: GPx activity was significantly higher overall in the case of MAP infection in both humans and cattle. The mean value for GPx activity was 1.59 +/- 0.65 units/ml in MAP positive cattle compared to 0.46907 +/- 0.28 units/ml in healthy cattle sera, where a unit was defined as one mmol/minute (P < 0.01). The mean value of the GPx activity in MAP negative humans clinical sera was 0.42367 +/- 0.229 units/ml compared to 0.80941 +/- 0.521 in MAP positive sera in a study comparing Crohn's disease patients to their healthy relatives. The mean activity in MAP negative humans was 0.4702 +/- 0.1299 compared to 0.6510 +/- 00.1665 units/ml in positive samples in a randomized field study of 100 subjects. CONCLUSION: This study demonstrated a strong correlation between MAP and the elevation of GPx activity. This was especially evident in Crohn's patients, which further supports the association of MAP and Crohn's disease. GPx activity may also be used to predict MAP infection status and to show that Crohn's disease patients who are infected with MAP have higher tendency to develop oxidative stress than Crohn's disease patients who are negative for the bacteria. PMID- 26997978 TI - Constructing and Adapting Causal and Formative Measures of Family Settings: The HOME Inventory as Illustration. AB - Measures of the home environment are frequently used in studies of children's development. This review provides information on indices composed of causal and formative indicators (the kind of indicators often used to capture salient aspects of family environments) and to suggest approaches that may be useful in constructing such measures for diverse populations. The HOME Inventory is used to illustrate challenges scholars face in determining what to include in useful measures of family settings. To that end, a cross-cultural review of research on relations among HOME, family context, and child outcomes is presented. The end of the review offers a plan for how best to further research on relations between the home environment and child development for diverse populations. PMID- 26997982 TI - Transforming growth factor-beta3 promotes facial nerve injury repair in rabbits. AB - The present study investigated the effects of transforming growth factor (TGF) beta3 on the regeneration of facial nerves in rabbits. A total of 20 adult rabbits were randomly divided into three equal groups: Normal control (n=10), surgical control (n=10) and TGF-beta3 treatment (n=10). The total number and diameter of the regenerated nerve fibers was significantly increased in the TGF beta3 treatment group, as compared with in the surgical control group (P<0.01). Furthermore, in the TGF-beta3 treatment group, the epineurial repair of the facial nerves was intact and the nerve fibers, which were arranged in neat rows, were morphologically intact with visible myelin swelling. However, in the surgical control group, the epineurial repair was incomplete, as demonstrated by: Atrophic nerve fibers, partially disappeared axons and myelin of uneven thickness with fuzzy borders. Electron microscopy demonstrated that the regenerated fibers in the TGF-beta3 treatment group were predominantly myelinated, with clear layered myelin sheath structures and axoplasms rich in organelles. Although typical layered myelin sheath structures were observed in the surgical control group, the myelin sheaths of the myelinated nerve fibers were poorly developed and few organelles were detected in the axoplasms. Neuro-electrophysiological examination demonstrated that, as compared with the surgical control group, the latency period of the action potentials in the TGF-beta3 treatment group were shorter, whereas the stimulus amplitudes of the action potentials were significantly increased (P<0.01). The results of the present study suggest that TGF-beta3 may improve the regeneration of facial nerves following trauma or injury. PMID- 26997981 TI - Genetic stability of pluripotent stem cells during anti-cancer therapies. AB - Regenerative medicine is a rapidly growing field that holds promise for the treatment of many currently unresponsive diseases. Stem cells (SCs) are undifferentiated cells with long-term self-renewal potential and the capacity to develop into specialized cells. SC-based therapies constitute a novel and promising concept in regenerative medicine. Radiotherapy is the most frequently used method in the adjuvant treatment of tumorous alterations. In the future, the usage of SCs in regenerative medicine will be affected by their regular and inevitable exposure to ionizing radiation (IR). This phenomenon will be observed during treatment as well as diagnosis. The issue of the genetic stability of SCs and cells differentiated from SCs is crucial in the context of the application of these cells in clinical practice. This review examines current knowledge concerning the DNA repair mechanisms (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining) of SCs in response to the harmful effects of genotoxic agents such as IR and chemotherapeutics. PMID- 26997984 TI - Alterations in the expression of protease-activated receptor 1 and tumor necrosis factor-alpha in the basilar artery of rats following a subarachnoid hemorrhage. AB - The present study aimed to investigate the expression of protease-activated receptor 1 (PAR1) and tumor necrosis factor (TNF)-alpha in a rat model of subarachnoid hemorrhage (SAH)-induced cerebral vasospasm (CVS). The rat models were established by twice injecting blood into the cisterna magna, after which the following experimental groups were established: The normal group, the SAH3d group, the SAH5d group and the SAH7d group. The rats were perfused and the basilar artery was removed for histological examination. The cross-sectional area of the basilar artery lumen was measured using computer software; and the protein expression of PAR1 and TNF-alpha was detected by immunohistochemistry. The cross sectional area of the basilar artery of the rats in the SAH model groups was significantly decreased in a time-dependent manner, as compared with the normal group. The protein expression of PAR1 and TNF-alpha in the SAH3d, SAH5d and SAH7d groups was significantly increased over time (P<0.05), as compared with the normal group. CVS was detected in the basilar artery, and was associated with wall thickening and significant narrowing of the lumen, thus suggesting that the present model may be used for investigating cerebrovascular disease following SAH. The immunohistochemical analyses demonstrated that the protein expression of PAR1 and TNF-alpha was significantly increased in the basilar artery of the SAH model rats, and were positively correlated with the degree of CVS. PMID- 26997983 TI - Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage. AB - The present study aimed to investigate the therapeutic effects of curcumin (CU) against brain edema in a rat model of hypoxia-hypercapnia (HH)-induced brain damage (HHBD). Male Sprague-Dawley rats were divided into five groups, including a control group and four treatment groups. The rats in the control group were raised under normal laboratory conditions and were injected with water, whereas the rats in the treatment groups were exposed to a low O2/high CO2 environment simulating HH conditions, and were injected with water, CU, dimethyl sulfoxide (solvent control) or monosialoganglioside GM1. After 2 weeks, the morphological characteristics of the brain tissues were analyzed using optical and electron microscopy. In addition, aquaporin (AQP)-4 protein expression levels in brain tissue samples were analyzed using streptavidin-biotin complex immunohistochemistry and western blotting, and mRNA expression levels were detected using reverse transcription-quantitative polymerase chain reaction. Severe brain edema, tissue structure disruption and increased AQP4 expression levels were detected in the brain tissues of the HH rats. Conversely, the rats treated with CU or GM1 exhibited attenuated HHBD-induced brain edema and tissue structure disruption, and decreased mRNA and protein expression levels of AQP4. The results of the present study suggested that CU treatment was able to attenuate HHBD-induced brain edema by downregulating the expression levels of AQP4 in a rat model. Therefore, CU may be considered a potential therapeutic drug for the treatment of patients with brain edema. PMID- 26997985 TI - Surfactant protein D, a clinical biomarker for chronic obstructive pulmonary disease with excellent discriminant values. AB - Biological markers can help to better identify a disease or refine its diagnosis. In the present study, the association between surfactant protein D (SP-D) and chronic obstructive pulmonary disease (COPD) was studied among subjects consulting for respiratory diseases or symptoms and was compared with C-reactive protein (CRP) and fibrinogen. A further aim of this study was to identify the optimal cut-off point of SP-D able to discriminate COPD patients. A case-control study including 90 COPD patients, 124 asthma patients and 180 controls was conducted. Standardized questionnaires were administered and lung function tests were performed. Biological markers were measured in blood samples according to standardized procedures. The association between SP-D and COPD was investigated using logistic regression models. Receiver-operating characteristic curves were used for threshold identification. SP-D levels above the median value were positively associated with COPD [adjusted odds ratio (OR)=3.86, 95% confidence interval (CI): 1.51-9.85, P=0.005). No associations with COPD or asthma were found for CRP or fibrinogen levels. Scores for COPD diagnosis in all COPD patients or ever-smoker COPD patients were identified (sensitivity, 76.4 and 77.8%; specificity, 89.3 and 88.5%, respectively). The results indicate that SP-D can differentiate COPD from other respiratory symptoms or diseases. Used with socio-demographic characteristics and respiratory symptoms, SP-D is able to discriminate COPD patients from controls, particularly among smokers. PMID- 26997986 TI - A three-year survey of the antimicrobial resistance of microorganisms at a Chinese hospital. AB - The present retrospective study aimed to investigate the antibiotic susceptibility of bacteria at Shanghai First People's Hospital (Shanghai, China) between 2009 and 2011. An increasing trend of antibiotic resistance was observed in this hospital between 2009 and 2011. Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus were the most prevalent resistant strains. Antimicrobial susceptibility was detected using standard Kirby-Bauer disk diffusion and analyzed using World Health Organization software. E. coli was demonstrated to be the most prevalent bacterium in the present survey between 2009 and 2011 (16.2, 20.0 and 19.6%, respectively); followed by A. baumannii (13.5, 13.3 and 10.6%, respectively) and S. aureus. Notably, >70% of E. coli and 70% of S. aureus were resistant to common antibiotics; whereas 60% of A. baumannii and 20% of Pseudomonas aeruginosa were resistant to the majority of the antibiotics investigated. In 2011, Enterococcus faecalis exhibited a resistance rate of 55.6% against levofloxacin and E. faecium exhibited a 53.2% resistance rate. The present survey demonstrated an increasing trend in bacterial resistance against antibiotics; therefore, more stringent guidelines for antibiotics should be advocated. PMID- 26997987 TI - Biotin-avidin mediates the binding of adipose-derived stem cells to a porous beta tricalcium phosphate scaffold: Mandibular regeneration. AB - The present study aimed to investigate the properties of a promising bone scaffold for bone repair, which consisted of a novel composite of adipose-derived stem cells (ADSCs) attached to a porous beta-tricalcium phosphate (beta-TCP) scaffold with platelet-rich plasma (PRP). The beta-TCP powder was synthesized and its composition was determined using X-ray diffraction and Fourier transform infrared spectroscopy. The surface morphology and microstructure of the fabricated porous beta-TCP scaffold samples were analyzed using light and scanning electron microscopy, and their porosity and compressive strength were also evaluated. In addition, the viability of rabbit ADSCs incubated with various concentrations of the beta-TCP extraction fluid was analyzed. The rate of attachment and the morphology of biotinylated ADSCs (Bio-ADSCs) on avidin-coated beta-TCP (Avi-beta-TCP), and untreated ADSCs on beta-TCP, were compared. Furthermore, in vivo bone-forming abilities were determined following the implantation of group 1 (Bio-ADSCs/Avi-beta-TCP) and group 2 (Bio-ADSCs/Avi-beta TCP/PRP) constructs using computed tomography, and histological osteocalcin (OCN) and alkaline phosphatase (ALP) expression analyses in a rabbit model of mandibulofacial defects. The beta-TCP scaffold exhibited a high porosity (71.26+/ 0.28%), suitable pore size, and good mechanical strength (7.93+/-0.06 MPa). Following incubation with beta-TCP for 72 h, 100% of viable ADSCs remained. The avidin-biotin binding system significantly increased the initial attachment rate of Bio-ADSCs to Avi-beta-TCP in the first hour (P<0.01). Following the addition of PRP, group 2 exhibited a bony-union and mandibular body shape, newly formed bone and increased expression levels of OCN and ALP in the mandibulofacial defect area, as compared with group 1 (P<0.05). The results of the present study suggested that the novel Bio-ADSCs/Avi-beta-TCP/PRP composite may have potential application in bone repair and bone tissue engineering. PMID- 26997988 TI - Expression, purification and identification of an immunogenic fragment in the ectodomain of prostate-specific membrane antigen. AB - The present study aimed to identify, express and purify an immunogenic fragment in the ectodomain of prostate-specific membrane antigen (PSMA) within a fusion protein. The PSMA amino acid sequence published in National Center for Biotechnology Information GenBank was used to determine sequence homology and immunogenic index analyses, additionally using BLASTN, Protean and ExPASy software to predict the polypeptide sequences of immunogenic epitopes. The gene sequence encoding the ectodomain of the polypeptide immunogenic fragments, containing the identified immunogenic epitopes, was generated using whole-gene synthesis. Prokaryotic expression vector pET-32a-r-ectodomain-PSMA was constructed and the recombinant plasmids were transformed into competent BL21 (DE3) Escherichia coli, which was followed by induction of recombinant protein expression using isopropyl-beta-D-thiogalactopyranoside. Fusion proteins were isolated and purified using affinity chromatography and their immune activity was subsequently investigated using western blot analysis. Purified protein was used to immunize BALB/c mice in order to generate polyclonal antibodies, and the binding of polyclonal antibodies to prostate cancer cell lines in vitro was evaluated using flow cytometry. A total of 3 polypeptide fragments with high specificity were identified following analysis using numerous software packages, and the gene sequences encoding regions containing the 2 most immunogenic fragments were synthesized and successfully inserted into the prokaryotic expression vector pET-32a-r-ectodomain-PSMA. The recombinant PSMA protein fragment had a molecular weight of ~50 kDa and 95% purity. Western blot analysis revealed that the r-ectodomain-PSMA fusion protein specifically bound to the anti PSMA ectodomain monoclonal antibody. Flow cytometry demonstrated that polyclonal antibodies raised against these recombinant proteins could specifically bind to PSMA-positive LNCaP cells, but not to PSMA-negative PC-3 cells. An immunogenic fragment in the ectodomain of PSMA was successfully expressed and purified. The present study, therefore, provides a basis for the preparation of an anti-PSMA small humanized monoclonal antibody. PMID- 26997989 TI - Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats. AB - Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required. PMID- 26997990 TI - Determining the critical effective temperature and heat dispersal pattern in monopolar radiofrequency ablation using temperature-time integration. AB - The radiofrequency ablation (RFA) lesion size is posited to be disproportionate to the total delivered energy, and temperature-time integration (TTI) may have a more critical effect on lesion size. The present study aimed to evaluate this hypothesis by determining the temperature threshold and temperature distribution over tissues during the RFA lesioning process. Using an ex vivo chicken tissue model and an in vivo rabbit model with RFA applied for 2 min under various target temperature settings, the resultant lesions were evaluated histologically using Masson's trichrome stain. The temperature distribution over the tissue during the RFA lesioning process was also determined using a VT02 Visual IR Thermometer. It was revealed that the thermal injury threshold for RFA in the chicken tissues was ~65 degrees C, but that it ranged from 55-65 degrees C in mammals. Using infra red thermal imaging, the temperature gradient (from the center to the periphery) during the RFA lesioning process demonstrated a uniform heat diffusion pattern. This data supports the proposed hypothesis that TTI is a critical parameter in determining RFA lesion size and can be applied clinically using the following equation: [Target temperature - 55 ( degrees C)] * time (sec) is proportional to RFA lesion size. PMID- 26997992 TI - Efficacy and effect of free treatment on multidrug-resistant tuberculosis. AB - Multidrug-resistant tuberculosis (MDR-TB) is a serious public health and social issue. It pertains to the type of tuberculosis that is resistant simultaneously to isoniazid and rifampicin. MDR-TB has a high mortality and is expensive to treat. The aim of the present study was to examine the therapeutic effects of individualized free treatment and the relevant influencing factors on the treatment outcome for MDR-TB. A prospective study module was used to analyze the therapeutic outcome of MDR-TB with individualized free treatment for 160 patients between 2011 and 2014. Statistical analysis was performed using the Chi-square or Fisher's exact test, and the odds ratio was calculated using a logistic regression analysis model. In total, 160 patients were enrolled in the study for treatment of MDR-TB. From these, 88 cases completed the course of treatment, and 70 cases were successfully treated. Of the remaining 72 cases, 37 cases exhibited treatment failure, 18 cases were suspended during treatment and 17 patients succumbed to the disease. The results showed that the confounding factors were: i) retreatment (p<0.05); ii) occurrence of diabetes (p<0.001); iii) lesion without improvement in radiography during treatment (p=0.001); iv) positive sputum culture for Mycobacterium tuberculosis after 3-month treatment (p<0.05); and v) termination of treatment due to adverse reaction (p<0.05). These factors were associated with poor treatment outcomes by logistic regression analysis. Adverse drug reaction was observed in 33 cases and treatment was terminated or changed permanently in 29 of these cases. The most common adverse reaction was liver function damage caused by pyrazinamide and leucopenia caused by rifabutin. One patient suffered from serious liver failure. In conclusion, the success rate of long treatment course for MDR-TB is not high due to many adverse reactions. Occurrence of diabetes is the main factor that caused poor efficacy. PMID- 26997991 TI - Early application of negative pressure wound therapy to acute wounds contaminated with Staphylococcus aureus: An effective approach to preventing biofilm formation. AB - Negative pressure wound therapy (NPWT) has been demonstrated to be effective at preventing biofilm-associated infections; however, its role in biofilm prevention is unknown. The present study evaluated the effect of NPWT on biofilm prevention when rapidly initiated following wound contamination. Full-thickness dermal wounds (8 mm) were created in rabbit ears and inoculated with green fluorescent protein-labeled Staphylococcus aureus (S. aureus). At 6 h following inoculation, continuous NPWT at -125 mmHg was initiated, with the wounds on the contralateral ear left untreated in order to serve as self-controls. S. aureus rapidly formed mature biofilms in the wound beds post-inoculation, with a persistent bacterial burden of ~105-107 colony-forming units (CFUs)/wound and impaired wound healing. Compared with the untreated group, NPWT resulted in a significant reduction in biofilm matrix, which was verified by scanning electron microscopy and epifluorescence. A reduction in bacterial counts followed (P<0.05) with ~103 CFUs/wound on postoperative day 13 and improvement in all healing parameters (P<0.05) relative to control wounds. The results of the present investigation suggest that NPWT is an effective strategy to impeding the formation of S. aureus wound biofilms when initiated rapidly following bacterial contamination. The early application of NPWT, aimed at biofilm prevention, may improve wound care. PMID- 26997993 TI - Surgical resection of vasoactive intestinal peptideoma with hepatic metastasis aids symptom palliation: A case report. AB - Vasoactive intestinal peptideoma (VIPoma) is a rare pancreatic endocrine tumor associated with a well-defined clinical syndrome characterized by watery diarrhea, hypokalemia and metabolic acidosis. In adults, VIPoma is most commonly found in the pancreas, with 80% of the tumors occurring in the body and tail and 20% occurring in the pancreatic head. VIPomas can represent a significant diagnostic challenge due to their nonspecific clinical presentation, which can result in the misdiagnosis of a VIPoma as another condition, such as laxative overdose or a carcinoid secreting tumor. Surgical clearance of the tumor is the first-line treatment, even in cases with metastasis. The present study describes the case of a patient who presented with chronic watery diarrhea and hypokalemia due to a tumor in the pancreatic head, which was confirmed to contain immunoreactive vasoactive intestinal polypeptide via immunohistochemistry. A hepatic metastasis lesion was diagnosed following computed tomography. Stable control of symptoms was achieved after surgery and drug treatment. The study additionally reviews the clinical, histological, radiological and diagnostic features of the condition, as well as the therapeutic modalities that can be used to treat VIPoma in the pancreatic head with hepatic metastasis. PMID- 26997994 TI - Enhancement of ICAM-1 via the JAK2/STAT3 signaling pathway in a rat model of severe acute pancreatitis-associated lung injury. AB - Acute lung injury (ALI), which is associated with severe acute pancreatitis (SAP), results from damage to the pulmonary microvascular endothelial cells (PMVECs), which in turn leads to high levels of inflammatory cytokines that destroy PMVECs. However, the molecular mechanisms underlying SAP-associated ALI (SAP-ALI) are currently not well understood. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the persistent migration and accumulation of neutrophils and macrophages, which in turn has been associated with the increased permeability of microvascular endothelial cells. Signal transduction via the Janus kinase-2 (JAK2)/signal transducer and activator of transcription-3 (STAT3) transcription factors has been shown to be involved in inflammation. The present study aimed to investigate the expression levels of ICAM-1 and JAK2/STAT3 signaling components in a rat model of SAP-ALI. SAP was induced in the rat model, and dexamethasone (DEX) was administered to the treatment group. Subsequently, ICAM-1, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha, JAK2, STAT3 and nuclear factor (NF)-kappaB mRNA expression levels were determined using reverse transcription-polymerase chain reaction; ICAM-1 protein expression levels were determined using western blotting; and IL-6, IL-8 and TNF-alpha levels were measured via an enzyme-linked immunosorbent assay. In addition, an immunohistochemical analysis of ICAM-1, NF-kappaB, JAK2 and STAT3 was conducted, and the protein expression and cell morphology of the lungs in all rats was analyzed. ICAM-1 mRNA and protein expression levels were significantly increased following induction of SAP, and were significantly decreased in the DEX-treated group. Furthermore, treatment with DEX significantly reduced serum expression levels of IL-6, IL-8 and TNF-alpha and decreased expression levels of NF-kappaB, JAK2 and STAT3 in the lung tissue, as compared with the untreated SAP group. The present study demonstrated that DEX treatment was able to suppress ICAM-1 mRNA and protein expression in a rat model of SAP-ALI via the inhibition of IL-6 and TNF-alpha-induced JAK2/STAT3 activation; thus suggesting that DEX treatment may be considered a potential strategy in the treatment of patients with SAP-ALI. PMID- 26997995 TI - Lipid-lysine adducts and modified tyrosines as markers of oxidative stress in the second trimester of pregnancy and their association with infant characteristics. AB - Pregnancy is a physiological state accompanied by excessive levels of oxidative stress (OS), due to the increased demand and utilisation of oxygen. There is increasing evidence that maternally augmented OS exerts an adverse effect on pregnancy outcome. The aim of the present prospective study was to determine the association between the urinary concentration of relatively novel OS markers measured in the second trimester of pregnancy and the infant characteristics at birth. The maternal levels of urinary hexanoyl-lysine (HEL), propanoyl-lysine (PRL), dityrosine (DiY) and 3-nitrotyrosine (NY) were evaluated in generally healthy pregnant subjects to determine their association with birth weight, gestation at delivery and Apgar score. The observed levels of the markers were in agreement with those measured in healthy non-pregnant subjects in a previous study. A positive correlation was detected between HEL and PRL, as well as between HEL and DiY. Although the absence of a correlation between NY and the other markers has been previously noted in a non-pregnant population, a positive correlation in the pair PRL-NY (r=0.367; P<0.001) was observed in the present study. Maternal cigarette smoking was associated with increased urinary PRL levels (P=0.034). The most notable observation in the present study was that high levels of PRL and NY were associated with low Apgar scores at 1 and 5 min after birth (OR, 1.098 and 2.084 for PRL and NY, respectively; P<0.05). However, poor predictive accuracy was shown. For NY, the following results were obtained: Area under the curve (AUC), 0.818; sensitivity, 100%; specificity, 57%; positive predictive value (PPV), 11.54%; and negative predictive value (NPV), 100%. For PLR the values were as follows: AUC, 0.802; sensitivity, 100%; specificity, 62.6%; PPV, 13.05%; and NPV, 100%. DiY was negatively associated with preterm birth risk (OR=0.703; P=0.028). In conclusion, the results of the present study indicated the presence of OS in the second trimester of pregnancy, which was detected with damage to lipids and proteins and associated with an adverse Apgar score; however, the selected urinary markers exhibited poor positive predictive efficacy. PMID- 26997996 TI - Severity and prognosis of acute organophosphorus pesticide poisoning are indicated by C-reactive protein and copeptin levels and APACHE II score. AB - The aim of the present study was to investigate the plasma levels of C-reactive protein (CRP) and copeptin, in addition to the acute physiology and chronic health evaluation II (APACHE II) scores, in patients with acute organophosphorus pesticide poisoning (AOPP). A total of 100 patients with AOPP were included and divided into mild, moderate and severe groups according to AOPP diagnosis and classification standards. Blood samples were collected from all patients on days 1, 3 and 7 following AOPP. The concentrations of CRP and copeptin in the plasma were determined using enzyme-linked immunosorbent assay. All AOPP patients underwent APACHE II scoring and the diagnostic value of these scores was analyzed using receiver operating characteristic curves (ROCs). On days 1, 3 and 7 after AOPP, the levels of CRP and copeptin were increased in correlation with the increase in AOPP severity, and were significantly higher compared with the control groups. Furthermore, elevated CRP and copeptin plasma levels were detected in patients with severe AOPP on day 7, whereas these levels were reduced in patients with mild or moderate AOPP. APACHE II scores, blood lactate level, acetylcholine esterase level, twitch disappearance time, reactivating agent dose and inability to raise the head were the high-risk factors that affected the prognosis of AOPP. Patients with plasma CRP and copeptin levels higher than median values had worse prognoses. The areas under curve for ROCs were 0.89, 0.75 and 0.72 for CRP levels, copeptin levels and APACHE II scores, respectively. In addition, the plasma contents of CRP and copeptin are increased according to the severity of AOPP. Therefore, the results of the present study suggest that CRP and copeptin levels and APACHE II scores may be used for the determination of AOPP severity and the prediction of AOPP prognosis. PMID- 26997997 TI - Circulating microRNA profile in patients with membranous obstruction of the inferior vena cava. AB - Membranous obstruction of the inferior vena cava (MOVC) is a common type of Budd Chiari syndrome. However, the pathogenesis of MOVC has not been fully elucidated. Recent studies demonstrated that microRNAs (miRNAs or miRs) are involved in multiple diseases. To the best of our knowledge, specific changes in the expression of miRNAs in MOVC patients have not been previously assessed. The present study used a microarray analysis, followed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation, with the aim to access the miRNA expression levels in the plasma of 34 MOVC patients, compared with those in healthy controls. The results revealed a total of 16 differentially expressed miRNAs in MOVC patients. Subsequently, RT-qPCR analysis verified the statistically consistent expression of 5 selected miRNAs (miR-125a-5p, miR-133b, miR-423-5p, miR-1228-5p and miR-1266), in line with the results of the microarray analysis. These 5 miRNAs, which were described as crucial regulators in numerous biological processes and vascular diseases, may play an important role in the pathogenesis of MOVC. Bioinformatics analysis of target genes of the differentially expressed miRNAs revealed that these predicted targets were significantly enriched and involved in several key signaling pathways important for MOVC, including the ErbB, Wnt, MAPK and VEGF signaling pathway. In conclusion, miRNAs may involve in multiple signaling pathways contributing to the pathological processes of MOVC. The present study offers an intriguing new perspective on the involvement of miRNAs in MOVC; however, the precise underlying mechanisms require further validation. PMID- 26997998 TI - Effect of the herbal formulation Jianpijiedu on the TCRVbetaCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative. AB - The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vbeta-chain complementarity determining region 3 (TCRVbetaCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVbetaCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVbetaCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVbetaCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL OHC-induced animals may be due to the promotion of the Ds values of the TCRVbetaCDR3 repertoire. PMID- 26997999 TI - Effectiveness and safety of laparoscopic Roux-en-Y gastric bypass for the treatment of type 2 diabetes mellitus. AB - Gastric bypass may be conducted to aid in glycemic control in adults with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the clinical results of diabetes remission and metabolic syndrome in individuals with T2DM after undergoing a gastric bypass. A total of 85 patients (39 men and 46 women) with T2DM underwent laparoscopic Roux-en-Y gastric bypass (LRYGB). Data regarding patient demographics, body mass index (BMI), co-morbidities and details of diabetes mellitus, including disease duration, remission, beta-cell function, blood lipid levels and nutritive status were prospectively collected and analyzed. The mean duration from the onset of T2DM was 7.79+/-4.84 years (range, 1 month to 22 years). The preoperative mean BMI was 31.60+/-4.10 (range, 28.53 48.10 kg/m2), mean percentage of body fat was 36.35+/-9.12% (range, 18-56%), and the mean HbA1c was 8.32+/-2.13% (range, 7-15.9%). Five patients (5.9%) developed complications without mortality. T2DM and beta-cell function were significantly improved from by month 6 after surgery (P<0.05). Improvements in central obesity, blood pressure (BP; systolic and diastolic) control, blood lipid levels were observed, without malnutrition or severe anemia. Therefore, the present results indicate that laparoscopic RYGBP is a safe and effective procedure for improving glycemic control, obesity, body fat percentage and BP in patients with T2DM and obesity. PMID- 26998000 TI - Anti-diabetic and anti-oxidative activity of fixed oil extracted from Ocimum sanctum L. leaves in diabetic rats. AB - Ocimum sanctum L. (OS) leaves have been shown to exert diverse potential benefits in a variety of stress conditions. The present study was conducted to elucidate the effects of the fixed oil extracted from OS leaves on the blood glucose levels and serum lipid profile of streptozotocin-induced diabetic rats. In addition, the anti-oxidative activity of OS leaves to protect various organs including the liver, kidney and heart was investigated. The fixed oil of the OS leaves was extracted using hexane, and the various fatty acid contents of the oil were determined using gas chromatography-mass spectrometry. Male Wistar rats were allocated into three groups (n=7 per group): Normal control rats, diabetic rats and diabetic rats fed daily with the fixed oil for three weeks. The results showed that alpha-linolenic acid was the primary fatty acid contained in the fixed oil of OS. After 3 weeks of diabetic induction, the rats exhibited increased blood glucose levels and serum lipid profile, in addition to elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase MB subunit (CK-MB), creatinine and blood urea nitrogen (BUN). The fixed oil significantly decreased the elevated levels of blood glucose, the serum lipid profile and the levels of serum creatinine and BUN (P<0.001), without exerting significant effects on the elevated serum levels of AST, ALT, LDH and CK-MB. Furthermore, the fixed oil increased the diabetically-reduced levels of serum insulin and decreased the rat kidney weight. Fixed oil suppressed the elevated thiobarbituric acid reactive substances (TBARS) level and increased the activity of various antioxidative enzymes in the rat renal tissue. By contrast, the fixed oil had no effect on the elevated TBARS level and the inhibited activity of the antioxidative enzymes in the rat liver and cardiac tissues. Histopathological results indicated that the fixed oil preserved the renal tissue against oxidative stress in diabetes. In summary, the results of the present study suggest that the fixed oil extracted from OS leaves exerted anti-hyperglycemic, anti-hyperlipidemic and free radical scavenging effects in diabetic rats, thus providing renal protection against diabetes. The alpha-linolenic acid contained in the fixed oil may be responsible for these effects. PMID- 26998001 TI - Significance of vaspin in obstructive sleep apnea-hypopnea syndrome. AB - Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a commonly-diagnosed chronic sleep disorder. It is considered to be an important independent risk factor in the development of insulin resistance (IR). Patients with OSAHS exhibit a variety of metabolic disorders, including obesity and metabolic syndrome. Visceral adipose tissue-derived serpin (vaspin) is an adipokine that is considered to be a link between obesity and IR. The present study aimed to evaluate the levels of plasma vaspin in patients with OSAHS and examine their potential correlation with sleep characteristics. A total of 20 healthy male subjects and 42 male patients with OSAHS were selected, and patients were divided into mild (n=22) and severe (n=20) OSAHS groups. The 20 patients in the severe OSAHS group received nasal continuous positive airway pressure (nCPAP) treatment for 2 months. Venous blood samples were drawn from all patients in a fasting state prior to and subsequent to nCPAP treatment, which were used to measure the levels of biochemical indicators. The sleep parameters and serologic index changes were compared prior to and following treatment. The values of contractive pressure (SBP), neck circumference (NC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI) and hip circumference (HC) in the two OSAHS groups were significantly increased compared with those in the control group. In addition, the levels of vaspin in OSAHS patients were markedly increased and vaspin was revealed to be positively associated with fasting blood sugar, fasting insulin, triglycerides, homeostasis model assessment-IR, apnea-hypopnea index (AHI), NC, WC, BMI and WHR (P<0.05). After 2 months of nCPAP treatment, the SBP and AHI were significantly reduced. In conclusion, vaspin may have an important role in OSAHS patients with IR and treatment using nCPAP may improve the condition of OSAHS patients. PMID- 26998002 TI - Effects of taxol resistance gene 1 expression on the chemosensitivity of SGC-7901 cells to oxaliplatin. AB - The present study aimed to evaluate the role of taxol resistance gene 1 (Txr1) in the development of oxaliplatin (L-OHP) resistance in gastric cancer (GC). Using SGC-7901 cells as a model, Txr1 was exogenously expressed or knocked down using small interfering RNA. Quantitative polymerase chain reaction (qPCR) and western blotting were performed to establish whether the Txr1 gene is involved in chemoresistance, and cell proliferation was assessed using an MTS assay. To this end, the mRNA and protein levels of Txr1, thrombospondin-1 and excision repair cross-complementing 1 protein were measured using qPCR and western blotting, respectively. Txr1-knockdown significantly increased the sensitivity of the SGC 7901 cells to L-OHP, whereas Txr1 overexpression promoted the resistance of the SGC-7901 cells to L-OHP. Exogenous Txr1 expression in the SGC-7901 cells induced L-OHP resistance, and the siRNA knockdown of Txr1 sensitized the human GC cells to L-OHP. Txr1 is, therefore, likely to play a role in L-OHP resistance, acting via TSP1, and should be investigated as a potential therapeutic target in the treatment of GC. PMID- 26998003 TI - Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials. AB - The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism. A search was conducted for appropriate randomized controlled trials and the data from 16 trials were pooled. The intended primary outcome of the present study was to determine the efficacy and safety of testosterone replacement therapy. The current data demonstrated that scores for Aging Male Symptoms (AMS) were significantly reduced following testosterone replacement therapy, with a mean decrease in AMS score of 1.52 [95% confidence interval (CI), 0.72 to 2.32; P=0.0002]. Testosterone replacement therapy increased lean body mass [mean difference (MD), 1.22; 95% CI, 0.33 to 2.11; P=0.007], reduced fat mass in a non significantly manner (MD, -0.85; 95% CI, -1.74 to 0.04; P=0.06) and significantly reduced total cholesterol (MD, -0.16; 95% CI, -0.29 to -0.03; P=0.01). No significant differences were identified in body weight (MD, 0.09; 95% CI, -1.13 to 1.31; P=0.89), body mass index (MD, 0.10; 95% CI, -0.62 to 0.82; P=0.78) or bone mineral density (MD, -0.01; 95% CI, -0.03 to 0.02; P=0.60). Average prostate volume increased (MD, 1.58; 95% CI, 0.6 to 2.56; P=0.002) following testosterone replacement therapy, but the levels of prostate-specific antigen (PSA) (MD, 0.10; 95% CI, -0.03 to 0.22; P=0.14) and the International Prostate Symptom Scores (MD, 0.01; 95% CI, -0.37 to 0.39; P=0.96) did not change. In conclusion, testosterone replacement therapy improves quality of life, increases lean body mass, significantly decreases total cholesterol, and is well-tolerated and safe for men with hypogonadism who are exhibiting PSA levels of <4 ng/ml. PMID- 26998004 TI - Expression profile analysis based on DNA microarray for patients undergoing off pump coronary artery bypass surgery. AB - Off-pump coronary artery bypass (OPCAB) surgery is the most effective treatment for coronary heart disease. The aim of this study was to explore the effects of OPCAB on the basis of the associated molecular mechanisms. GSE12486 expression profiles downloaded from the Gene Expression Omnibus database (GEO) were analyzed to identify the differentially expressed genes (DEGs). Principal component analysis (PCA) was conducted based on the expression profiles of DEGs. Function and pathway enrichment of upregulated DEGs was performed, followed by protein protein interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) was used for miRNA enrichment analysis based on expression profiles and prediction of their association with the disease. Cytoscape was applied to construct miRNA regulatory networks of DEGs. In total 64 DEGs were identified, including 63 upregulated and 1 downregulated gene. The first principal component in the PCA analysis was able to distinguish between pre- and post-OPCAB samples. Upregulated DEGs mainly enriched 20 Gene Ontology terms, such as chemokine activity, and 5 pathways including the chemokine signaling pathway. The constructed PPI network contained 234 edges and 55 nodes, and 10 upregulated hub nodes, including FBJ murine osteosarcoma viral oncogene homolog (FOS), were screened. A total of 36 miRNAs, including MIR-224 and MIR-7, were screened by GSEA enrichment analysis. A miRNA regulatory network including 176 edges and 97 nodes was constructed, showing the regulatory relationships between miRNAs and DEGs. For example, early growth response 2 (EGR2) was regulated by 8 miRNAs including MIR-150, MIR-142-3P, MIR-367 and MIR-224. The identified DEGs might play important roles in patients pre- and post-OPCAB surgery via the regulation of associated genes. PMID- 26998005 TI - Central retinal artery pressure and carotid artery stenosis. AB - The central retinal artery (CRA), which can be non-invasively examined with ophthalmoscopy, may be regarded as an extracranial part of the cerebrovascular system. Assessment of CRA pressure may be of help in assessing the impediment of the intracranial blood circulation in patients with a carotid artery stenosis (CAS). The aim of this study was to explore the potential associations between diastolic central retinal artery pressure (diastCRAP) and CAS. The prospective longitudinal clinical observational study included patients with CAS and a control group without CAS. diastCRAP was assessed using ophthalmodynamometry. The study group consisted of 95 patients with CAS (50 of whom had >75%CAS and underwent surgery; the surgical study group) and a control group of 64 individuals without CAS. In all study participants, a lower diastCRAP was significantly associated with a higher degree of CAS (P<0.001). Multivariate analysis indicated that a higher CAS degree was significantly (correlation coefficient: r=0.75) associated with a higher brachial diastolic blood pressure (P<0.001) and lower diastCRAP (P<0.001). Within the surgical study group at the baseline of the study, diastCRAP was significantly lower at the surgical side than at the contralateral side (P=0.02). The diastCRAP on the surgical side increased significantly (P<0.001) after surgery. In the surgical study group at baseline, diastCRAP on the surgical side was not significantly associated with brachial diastolic blood pressure (P=0.22), whereas after surgery, diastCRAP was significantly associated with brachial diastolic blood pressure (P=0.001). DiastCRAP was found to be significantly and linearly correlated with the degree of CAS in intra-individual inter-eye, inter-individual and intra-individual follow-up comparisons. The strong and linear association between diastCRAP and the degree of CAS suggest that diastCRAP should be explored further for use as an indicator of cerebrovascular status. PMID- 26998006 TI - CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice. AB - Dendritic cells (DCs) are associated with the activation and differentiation of T helper (Th) cells. Cluster of differentiation (CD)80 and CD86, the co-stimulatory molecules highly expressed in DCs, have are prominent in promoting the differentiation of Th cells toward Th2 cells. However, little is known about the effect of CD80 and CD86 knockdown on Th1/Th2 cytokine production in mature DCs (mDCs). The aim of the present study was to investigate whether small-interfering RNA (siRNA) could suppress the surface expression of CD80 and CD86 in mDCs. The effects of CD80 and CD86 knockdown in mDCs on Th1/Th2 cytokine expression were examined using an asthmatic murine model. DCs were isolated, separated and cultured in vitro. Flow cytometry was used to examine the expression of CD11c, CD80 and CD86 on the DCs. The DCs were transfected with CD80- and CD86-specific siRNA, while non-siRNA and negative siRNA controls were also designed. Then, the mRNA and protein expression levels of CD80 and CD86 were determined by reverse transcription-quantitative polymerase chain reaction and flow cytometry, respectively. The levels of interferon (IFN)-gamma and interleukin (IL)-4 produced by T cells co-cultured with mDCs were measured by enzyme-linked immunosorbent assay. Substantial downregulation of CD80 and CD86 mRNA and protein levels were observed in the mDCs following transfection with siRNA. The level of IFN-gamma produced by T cells co-cultured with mDCs was significantly increased in the siRNA group, while IL-4 production was significantly decreased. These results show that specific targeting of CD80 and CD86 with siRNA is able to suppress CD80/CD86 expression and consequently regulate Th1/Th2 cytokine levels by increasing IFN-gamma production and decreasing IL-4 levels in an asthmatic murine model. PMID- 26998007 TI - Investigation into the cause of mortality in 49 cases of idiopathic inflammatory myopathy: A single center study. AB - Idiopathic inflammatory myopathy (IIM) is an autoimmune disease characterized by chronic muscle weakness and myositis with unknown etiology. IIM may affect the function of multiple organs and has a poor prognosis. In the present study, the causes of mortality in patients with IIM admitted to the Xiangya Hospital during the last 14 years were investigated. The investigation included an analysis of frequent causes of IIM, and of infections and associated complications. A cohort study was conducted on 676 patients with IIM that were admitted to Xiangya Hospital from January, 2001 to January, 2015. There were 49 patient mortalities (7.2% of the total cases), of which 34 mortalities were infection-associated and 15 were not infection-associated. The proportion of infection-associated IIM mortalities had increased since 2001. Of the 34 infection-associated mortalities, 31 cases (63.3%) were of fungal and bacterial infections, most frequently infecting the lungs and the blood. Klebsiella pneumoniae and Acinetobacter baumannii were the most commonly isolated pathogens, and co-infection with the two pathogens was observed in the majority of cases. In the IIM mortalities not associated with infection, there were 2 acute myocardial infarction cases, 2 acute interstitial lung disease cases, 4 malignancies and 1 case of each of the following: Arrhythmia, pneumothorax, ventilator weakness, pulmonary artery hypertension, gastrointestinal bleeding, liver failure and renal failure. Three mortalities were secondary to viral hepatitis in the present study. Pathogenic infection was the most frequent cause of mortality in patients with IIM. The remaining causes of mortality included secondary to heart failure, lung dysfunction and malignancy. Following the ubiquitous application of glucocorticoids and immunosuppressants, the proportion of infection-associated mortalities increased in patients with IIM. Thus, in addition to focusing on the primary disease, infection should receive increased attention during clinical practice. PMID- 26998008 TI - Clinical effects of combined treatment by optimal dose of furosemide and spironolactone on diastolic heart failure in elderly patients. AB - Diastolic heart failure (DHF) is characterized by symptoms including reduced ventricular relaxation and compliance, resulting in congestion of pulmonary and systemic circulation. The curative effects of regular cardiac agents are ineffective. Thus, new agents are required to treat chronic cardiac failure. The aim of the present study was to examine the clinical effects of the combined treatment by optimal dose of furosemide (20 mg/day) and spironolactone (40 mg/day) on elderly patients with diastolic heart failure (DHF) [New York Heart Association (NYHA) 1-2 grade]. A total of 93 patients diagnosed with DHF between February, 2013 and February, 2014 were enrolled in the present study. The patients were randomly divided into the furosemide group (20 mg/day, n=27), optimal dose group (20 mg/day furosemide+40 mg/day spirolactone, n=36), and large dose group (40 mg/day furosemide+100 mg/day spirolactone, n=30). Following treatment for one month, a comparison and analysis of the NYHA class, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD), left ventricular wall segmental motion among the three groups were performed. The re-hospitalization rate of heart failure and incidence of electrolyte disorder among the three groups was compared and their differences analysed. Compared with pretreatment, the NYHA classifications of the three groups after treatment were reduced and differences were statistically significant (P<0.05). By contrast, for the NYHA classification after treatment there was no statistical significance (P>0.05). Compared with pretreatment, LVEF of the optimal dose group increased, LVEDD decreased, and the average systolic myocardial peak velocity and early diastolic myocardial peak velocity of ventricular wall motion were reduced, with differences being statistically significant (P<0.05). By contrast, in the furosemide and large dose groups no statistical significance was identified before and after the treatment (P>0.05). Improvement of the optimal dose group following treatment was more significant than the remaining two groups, and differences were statistically significant (P<0.05). The re-hospitalization rate of heart failure and incidence of electrolyte disorder in the optimal dose group following treatment were significantly less than the other two groups, and differences were statistically significant (P<0.05). In conclusion, the optimal dose (20 mg/day furosemide+40 mg/day spirolactone) significantly improved the clinical symptoms of elderly DHF patients (NYHA 1-2 grade) and ameliorated their long-term prognosis. PMID- 26998010 TI - Peritumoral cystic meningioma: A report of two cases and review of the literature. AB - The present study reported two cases of cystic meningioma. The clinical manifestations, magnetic resonance imaging (MRI) scan and histological aspects of the lesion and the associated cyst were examined. The classification of cystic meningioma was also discussed. The present study focused on the formation, diagnosis and management of the peritumoral cystic meningioma, and aimed to clarify certain contradictions in the literature concerning the formation of the peritumoral cyst meningioma: MRI alone is inadequate to determine the type of cystic meningioma, or to identify neoplastic cells on the cystic wall. In conclusion, surgical removal of the entire cyst is recommended in peritumoral cyst meningioma. PMID- 26998009 TI - Assessment of the redox status in patients with metabolic syndrome and type 2 diabetes reveals great variations. AB - The aim of the present study was to examine the effectiveness of a new redox status marker, the static oxidation reduction potential (sORP), for assessing oxidative stress in 75 patients with metabolic syndrome (MetS) and type 2 diabetes (T2D). A total of 35 normal subjects were used as the controls. Moreover, conventional markers of oxidative stress were assessed, such as thiobarbituric acid reactive substances (TBARS), protein carbonyls, the total antioxidant capacity in plasma, glutathione (GSH) levels and catalase (CAT) activity in erythrocytes. The results revealed that sORP was significantly higher (by 13.4%) in the patients with MetS and T2D compared to the controls, indicating an increase in oxidative stress. This finding was also supported by the significantly lower levels (by 27.7%) of GSH and the higher levels (by 23.3%) of CAT activity in the patients with MetS and T2D compared to the controls. Moreover, our results indicated a great variation in oxidative stress markers between the different patients with MetS and T2D, particarly as regards the GSH levels. Thus, the patients with MetS and T2D were divided into 2 subgroups, one with low GSH levels (n=31; GSH <3 umol/g Hb) and another with high GSH levels (n=35; GSH >4 umol/g Hb). The comparison of the markers between the 2 subgroups indicated that in the low GSH group, the GSH levels were significantly lower (by 51.7 and 52.9%) than those in the high GSH group and the controls, respectively. Furthermore, sORP in the low GSH group was significantly higher (by 8.1%) compared to the high GSH group, suggesting its sensitivity for assessing oxidative stress in patients wtih MetS and T2D. Moreover, this variation in oxidative stress levels between the different patients with T2D suggests that the assessment of the redox status may be important in prediabetic conditions, since there is evidence indicating that differences in the redox status in pre-diabetes may result in different outcomes. PMID- 26998013 TI - Lumican as a novel potential clinical indicator for acute aortic dissection: A comparative study, based on multi-slice computed tomography angiography. AB - The aim of the present study was to investigate the association between serum lumican levels and acute aortic dissection (AAD) severity. A total of 82 patients with chest or back pain and 30 healthy volunteers were recruited. Among the patients, there were 70 cases of AAD and 12 cases of intramural hematoma (IMH). AAD severity was determined using multi-slice computed tomography angiography (MSCTA). Serum was collected from the patients upon admission, and lumican levels were detected using an enzyme-linked immunosorbent assay. In addition, correlation analyses were conducted between lumican levels and AAD severity by designing a 'SCORE X, RANGE Y' system to measure the number of affected vital arteries and vertical range of false lumen, based on the MSCTA. Lumican levels differed significantly among the AAD patients (2.32+/-4.29 ng/ml), IMH patients (0.72+/-0.32 ng/ml) and healthy volunteers (0.85+/-0.53 ng/ml; P=0.003). In the AAD patients presenting within 12-72 h of symptom onset, the Spearman's rho correlation coefficient between lumican and SCORE or RANGE was 0.373 (P=0.046) and 0.468 (P=0.010), respectively. The present results suggest that lumican may be a potential marker for aiding the diagnosis and screening for AAD, and may be used to predict the severity of AAD. PMID- 26998011 TI - Effect of a quality-controlled fermented nutraceutical on skin aging markers: An antioxidant-control, double-blind study. AB - The aim of the present study was to determine whether oral supplementation with a fermented papaya preparation (FPP-treated group) or an antioxidant cocktail (antioxidant-control group, composed of 10 mg trans-resveratrol, 60 ug selenium, 10 mg vitamin E and 50 mg vitamin C) was able to improve the skin antioxidant capacity and the expression of key skin genes, while promoting skin antiaging effects. The study enrolled 60 healthy non-smoker males and females aged 40-65 years, all of whom showed clinical signs of skin aging. The subjects were randomly divided into two matched groups, and were administered FPP or antioxidant treatment of a 4.5 g/day sachet sublingually twice a day for 90 days in a double-blind fashion. The parameters investigated were: Skin surface, brown spots, skin evenness, skin moisturization, elasticity (face), redox balance, nitric oxide (NO) concentration, and the expression levels of key genes (outer forearm sample). As compared with the baseline (day 0) and antioxidant-control values, FPP-treated subjects showed a significant improvement in skin evenness, moisturization and elasticity. The two treatments improved the MDA and SOD skin concentrations, but only the FPP-treated group showed a higher SOD level and a significant NO increase, along with significant upregulation of acquaporin-3 and downregulation of the potentially pro-aging/carcinogenetic cyclophilin-A and CD147 genes (P<0.05). Progerin was unaffected in both treatment groups. In conclusion, these findings suggest that orally-administered FPP showed a consistent biological and gene-regulatory improvement in the skin, as was also demonstrated in previous experimental and clinical trials testing other tissues, while common oral antioxidants had only a minor effect. PMID- 26998012 TI - Increased expression of microRNA-503 and reduced expression of kangai-1 in B-cell non-Hodgkin's lymphoma. AB - The aim of the present study was to determine the expression levels of microRNA 503 (miR-503) and the tumor suppressor gene, kangai-1 (KAI1), in B-cell non Hodgkin's lymphoma (B-NHL). A total of 45 patients with B-NHL (including 29 cases with stage III/IV disease and 16 cases with stage I/II disease) were enrolled in this study. In addition, 26 patients with reactive lymphoid hyperplasia (RLH) were enrolled as the control patients. Reverse transcription-quantitative polymerase chain reaction was performed in order to measure the expression levels of miR-503 in B-NHL and RLH tissues, and to detect the expression levels of miR 503 and KAI1 in peripheral blood samples. In addition, KAI1 expression levels in B-NHL and RLH tissues were detected using western blotting and immunohistochemical analysis. The expression levels of miR-503 were found to be significantly increased in the tissues and peripheral blood of B-NHL patients when compared with those in RLH patients (P<0.05). However, KAI1 was strongly expressed in RLH tissues and weakly expressed in B-NHL tissues. Furthermore, the expression levels of KAI1 were significantly decreased in the tissues and peripheral blood of B-NHL patients when compared with those in the tissues and peripheral blood of RLH patients (P<0.05). The expression levels of miR-503 in the tissues and peripheral blood of patients with stage III/IV B-NHL were significantly higher compared with those with stage I/II B-NHL (P<0.05). By contrast, the expression levels of KAI1 in stage III/IV B-NHL tissues were significantly higher compared with those in stage I/II B-NHL tissues (P<0.05). In conclusion, miR-503 was highly expressed, whereas KAI1 was poorly expressed, in the tissues and peripheral blood of B-NHL patients. Thus, miR-503 may have an application as a novel therapeutic and diagnostic marker in B-NHL patients. PMID- 26998014 TI - Case report: Real-time contrast-enhanced ultrasonography for the diagnosis of typical 'bull's eye' sign of hepatic abscess caused by Acinetobacter baumannii in a tumor patient. AB - The present case report details a unique case of a 51-year-old male patient who underwent a radical operation for carcinoma of the stomach and pancreaticoduodenectomy. Conventional ultrasonography examination exhibited a characteristic 'bull's eye' sign in the liver; whereas real-time contrast enhanced ultrasonography (CEUS) demonstrated the patient was suffering from a hepatic abscess, corroborated by cytologic examination, which confirmed the presence of Acinetobacter baumannii. The hepatic localization of A. baumannii is rare in tumor patients presenting with a typical 'bull's eye' sign; and such a case could easily be misdiagnosed as hepatic metastasis. The findings presented in this case report demonstrate that real-time CEUS may offer important diagnostic elements, albeit not specific, which should, together with a positive cytologic test, confirm the diagnosis of a hepatic abscess. PMID- 26998016 TI - Cerebral venous malformation with meningioma: A case report. AB - A 43-year-old female patient was admitted to The First Hospital of Jilin University (Changchun, China) on 1st October 2011 with a 10-day history of discontinuous, whole-brain headache and a 1-year history of impaired vision and memory deterioration, accompanied by right facial numbness. Clinical signs and radiological features observed using magnetic resonance imaging (MRI) led to the diagnosis of an intracranial meningioma accompanied by a cerebral venous malformation (CVM). The patient underwent neurosurgical resection of the meningioma, but required no further treatment for the CVM. At a 1-year follow-up examination, the patient continued to complain of discontinuous headache. Digital subtraction angiography (DSA) was used to reconfirm the CVM diagnosis; however, no treatment was administered due to the high risks of treatment and only mild symptoms experienced by the patient. The present case demonstrates the efficacy of DSA for detecting the presence and specific nature of CVM, and compares the value of MRI and DSA in the diagnosis of CVM. The majority of CVM patients exhibit no clinical symptoms, and the disease prognosis is typically favorable. PMID- 26998015 TI - Fast-track surgery and exclusive enteral nutrition applied to a rat model of heterotopic intestinal transplantation. AB - The present study applied fast-track surgery (FTS) concepts and exclusive enteral nutrition (EEN) to a rat model of heterotopic intestinal transplantation (HIT). A total of 96 pairs of Sprague-Dawley rats were randomly distributed into three groups, as follows: i) The conventional group (group 1); ii) the FTS group (group 2); and iii) the FTS with EEN group (EEN group). FTS alterations to the HIT protocol were as follows: i) The use of sevoflurane as an anesthetic; ii) alterations to the order of the procedure and iii) a modified suturing technique. In addition, the EEN group rats underwent an early EEN gavage. The operation time, success rate, recovery state and morphological characteristics of the grafts were compared among the groups. The average operative time was significantly decreased in the group 2 and EEN group rats (137.44+/-16.03 and 139.67+/-15.25 min, respectively), as compared with the group 1 rats (169.36+/ 13.72 min; P<0.05). In addition, the percentage of rats surviving >14 days was significantly increased in the group 2 (87.5%) and EEN group (90.6%) rats, as compared with the group 1 rats (68.7%; P<0.05). Furthermore, the villi of graft in EEN group appeared longer, and exhibited narrower interspaces. The ischemia reperfusion injury and mononuclear cell infiltration were attenuated at postoperative day 7. The results of the present study suggested that the application of FTS concepts and EEN gavage to HIT may accelerate recovery and ameliorate graft damage following surgery. PMID- 26998017 TI - Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea. AB - The aim of the present study was to investigate the effects of lactadherin on plasma D-lactic acid and small intestinal mucin (MUC) 2 and claudin-1 expression levels in rats with diarrhea induced by rotavirus (RV) infection. A total of 75 seven-day-old healthy Sprague-Dawley rats were randomly divided into the following five groups: Control (C), RV infection (RVI), lactadherin before rotavirus infection (LBRI), lactadherin after rotavirus infection (LARI), and blank (B). On day 4 of artificial feeding, the rats in groups RVI, LBRI and LARI were intragastric administered 1*106 PFU RV; whereas the rats in groups C and B were intragastrically administered an equal volume of maintenance solution from the RV supernatant and normal saline, respectively. In the LBRI and LARI groups, rats received daily intragastric administration of 0.25 mg lactadherin for three days prior to and following infection with RV, respectively. The course of diarrheal symptoms was observed in each group and samples were collected on days 1, 4, and 7 post-infection in order to determine the mucosal morphology, plasma D lactic acid levels and the expression levels of MUC2 and the intracellular junction protein, claudin-1, in the small intestine. On day 4 post-infection, the rats in group RVI demonstrated severely damaged small intestines and typical diarrheal characteristics, as detected by light microscopy; whereas rats in groups LBRI and LARI demonstrated intact small intestinal villi with partial vacuolation of epithelial cells and changes in the position of their nuclei. Electron microscopy demonstrated that the rats in the RVI group had sparse, shortened, disordered intestinal microvilli and widened intercellular junctions; whereas those in groups LBRI and LARI had long intestinal microvilli sparser compared with groups B and C and slightly widened intercellular junctions. Plasma D-lactic acid levels were increased in groups RVI, LBRI and LARI, as compared with groups B and C, and the greatest levels were detected in the RVI group on days 1, 4 and 7 post-infection. In addition to maintaining intestinal permeability, lactadherin enhanced the expression levels of MUC2 and reduced the expression of claudin-1; therefore, further protecting the intestinal epithelial barrier, which may contribute to the prevention and treatment of diarrhea induced by infection with RV. PMID- 26998018 TI - Low expression of microRNA-202 is associated with the metastasis of esophageal squamous cell carcinoma. AB - The present study aimed to determine the expression levels and biological functions of microRNA-202 (miR-202) in patients with esophageal squamous cell carcinoma (ESCC). A total of 60 patients with ESCC and 30 healthy individuals were enrolled and reverse transcription-quantitative polymerase chain reaction was performed to measure the expression levels of miR-202. In order to investigate the effects of miR-202 expression levels on the proliferative, migratory and invasive abilities of ESCC cells, methylthiazolyl-tetrazolium bromide proliferation, in vitro scratch and Transwell(r) chamber assays were performed. Expression levels of miR-202 were significantly decreased in the peripheral blood of patients with ESCC, which is associated with the degree of cell differentiation and lymph node metastasis (P<0.05). Following miR-202 transfection, cell proliferation was significantly inhibited (P<0.05). Cell migration and invasion was also significantly inhibited by miR-202 transfection (P<0.05). The results of the present study demonstrated that the expression of miR-202 inhibited the proliferation, migration and invasion of ESCC cells. Furthermore, low expression levels of miR-202 were detected in the peripheral blood of patients with ESCC, which is associated with the development, invasion and metastasis of ESCC. PMID- 26998019 TI - Acute arrest of hematopoiesis induced by infection with Staphylococcus epidermidis following total knee arthroplasty: A case report and literature review. AB - Infection is one of the most severe complications of total knee prosthesis implantation. The present study reported the case of a 74-year-old female that developed a Staphylococcus epidermidis infection following a cemented total knee arthroplasty. A routine blood test revealed neutropenia and anemia, while S. epidermidis was detected in the peripheral blood and bone marrow. In the present case, S. epidermidis infection led to acute arrest of hematopoiesis (AAH), also known as aplastic crisis, which is the temporary cessation of red cell production. The development of AAH secondary to S. epidermidis infection is rare and, to the best of our knowledge, this is the first case reported in the literature. The present study increased our knowledge of this rare disease and its characteristics, which will enable physicians to be aware of the development of AAH as a rare complication of S. epidermidis infection. PMID- 26998020 TI - Inhibition of mTOR promotes hyperthermia sensitivity in SMMC-7721 human hepatocellular carcinoma cell line. AB - The mammalian target of rapamycin (mTOR) is a critical mediator of the phosphoinositide 3-kinase/protein kinase B/mTOR signaling pathway, and mTOR activity is induced following heat shock. Thermotherapy is used to treat hepatocellular carcinoma (HCC). However, the role of mTOR in modulating thermosensitivity in HCC has yet to be elucidated. In the present study, the antisense plasmid pEGFP-C1-mTOR was transfected into SMMC-7721 cells, and the expression levels of mTOR were analyzed by reverse transcription-polymerase chain reaction and western blot analysis. The thermal responses of the transfected cells were also examined. The results revealed that SMMC-7721 cells were sensitive to heat treatment, and cell viability was significantly inhibited following hyperthermia treatment (P<0.01). The mRNA and protein expression levels of mTOR decreased post-transfection. Cell proliferation, colony-forming ability and motility were all significantly decreased following hyperthermia treatment in the transfected cells. Flow cytometry analysis demonstrated that apoptosis was significantly increased following treatment (P<0.01). The number of cells in S phase was increased, and the cell cycle was arrested in S phase. In conclusion, inhibition of mTOR increased the thermosensitivity of SMMC-7721 cells by increasing cellular apoptosis and inducing S phase arrest. PMID- 26998021 TI - Transient severe left ventricular dysfunction following percutaneous patent ductus arteriosus closure in an adult with bicuspid aortic valve: A case report. AB - The present study reported the case of a 60-year-old female with patent ductus arteriosus (PDA) and a bicuspid aortic valve, who presented with transient severe left ventricular (LV) dysfunction following percutaneous closure of PDA, as identified by speckle tracking analysis. Transient LV dysfunction following PDA closure has previously been reported; however, severe LV dysfunction is rare. In the present case, the combination of a large PDA size, large amount of shunting, LV remodeling and bicuspid aortic valve may have induced serious deterioration of LV function following PDA closure. Furthermore, speckle-tracking echocardiography may be useful in the estimation of functional alterations in the myocardium of the LV following PDA closure. The observations detailed in the present study may improve the understanding of the pathophysiology and myocardial patterns of transient left ventricular dysfunction following PDA closure in adult humans. PMID- 26998022 TI - Regulatory effect of Bcl-2 in ultraviolet radiation-induced apoptosis of the mouse crystalline lens. AB - The aim of the present study was to analyze the role of Bcl-2 during the process of apoptosis in the mouse crystalline lens. In total, 12 normal mice served as the control group and 12 Bcl-2 knockout (K.O) mice served as the experimental group. The mouse crystalline lens was sampled for the detection of Bcl-2 and caspase-3 expression following exposure to ultraviolet (UV) radiation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine Bcl-2 expression in the groups of normal mice receiving UV radiation or not receiving UV radiation. Samples of the murine crystalline lens were microscopically harvested and analyzed using western blotting. Apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Furthermore, caspase 3 activity was examined using enzyme-linked immunosorbent assay kits, and RT-qPCR was used to analyze caspase-3 expression levels. The results of the present study demonstrated that there was no statistically significant difference in the level of Bcl-2 gene transcription between the two groups. In addition, UV radiation did not change the macrostructure of the crystalline lens in the group of normal mice or the group of Bcl-2 K.O mice. The results of the TUNEL assay indicated that the normal-UV group exhibited a more significant apoptosis level compared with the Bcl-2 K.O-UV group. Furthermore, the mRNA expression level of caspase-3 in the normal-UV group was significantly higher compared with the normal-nonUV group (P<0.05), while the levels in the Bcl-2 K.O-UV group were significantly higher compared with the Bcl 2 K.O and normal-nonUV groups (P<0.05). In addition, the mRNA expression level of caspase-3 was significantly higher in the normal-UV, as compared with the Bcl-2 K.O-UV group (P<0.05), and the variation trends in caspase-3 activity were consistent. In conclusion, the results of the present study demonstrated that Bcl 2 may have an important role in the promotion of UV-induced apoptosis in the crystalline lens. PMID- 26998023 TI - Berberine attenuates myocardial ischemia reperfusion injury by suppressing the activation of PI3K/AKT signaling. AB - Berberine (BBR), an isoquinoline alkaloid originally isolated from the Chinese herb Coptis chinensis (Huanglian), exhibits anti-inflammatory and immunosuppressive properties. Since myocardial ischemia/reperfusion (I/R) injury is associated with an excessive immune response, the current study was conducted to investigate the impact of BBR on myocardial I/R injury, a common disorder in clinical settings. Preconditioning of Sprague-Dawley rats with BBR (100 mg/kg/day, by gavage) for 14 days prior to the induction of I/R significantly attenuated myocardial I/R injury as manifested by a reduction in the incidence of ventricular arrhythmia and the amelioration of myocardial histological changes. These effects were found to be associated with the suppression of the phosphoinositide 3-kinase/AKT signaling pathway and the subsequent reduction of the expression of interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha in the serum and myocardial tissue. These results indicate that BBR has the potential be an effective alternative therapy for the prevention and treatment of myocardial I/R injury in clinical practice. PMID- 26998024 TI - Aggressive muscle-invasive bladder cancer with sarcomatoid differentiation in a 10-year-old girl: A case report. AB - The present study reports an unusual case of high-grade bladder cancer in a 10 year-old girl who complained of painless hematuria and urinary frequency. The tumor displayed sarcomatoid differentiation and an aggressive behavior, which required the administration of adjuvant chemotherapy. However, the disease progressed and the patient succumbed 6 months after surgery. It is known that the majority of malignant bladder cancers in pediatric patients are low-grade and present at an early stage, whereas sarcomatoid differentiation in the setting of a high-grade urothelial carcinoma is indicative of a poor prognosis. It is important that gross hematuria in pediatric patients is investigated carefully. It is recommended that the management of urothelial neoplasia in young patients should be predominantly decided on the basis of the grade and stage of the tumor rather than the age of the patient. PMID- 26998025 TI - Single-center study on transplantation of livers donated after cardiac death: A report of 6 cases. AB - Effective use of all available donated organs is critical, in order to meet the increasing demand for transplants. The present study explored liver transplantation with livers that were donated following cardiac death (DCD). According to the guidelines established by The Red Cross Society of China, 42 DCD organs were procured. Selected donors were treated with extracorporeal membrane oxygenation (ECMO) prior to the organ retrieval. The present single-center study included 6 liver transplantations of DCD organs (5 liver transplants and 1 liver kidney combined transplant). All 6 recipients had a successful recovery without significant complications. The serum alanine transaminase, total bilirubin and international normalized ratio returned to the normal levels within a short period of time following transplantation, and the liver function remained normal during the follow-up period, which lasted up to 24 months. The present report demonstrated the feasibility of orthotopic liver transplantation using DCD livers. The pre-conditioning DCD donors and optimization of the recipient's condition using ECMO, played a crucial role in ensuring the success of transplantation. PMID- 26998026 TI - Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema. AB - The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease. PMID- 26998027 TI - Curcumin suppresses transforming growth factor-beta1-induced cardiac fibroblast differentiation via inhibition of Smad-2 and p38 MAPK signaling pathways. AB - The differentiation of cardiac fibroblasts (CFs) into myofibroblasts and the subsequent deposition of the extracellular matrix is associated with myocardial fibrosis following various types of myocardial injury. In the present study, the effect of curcumin, which is a pharmacologically-safe natural compound from the Curcuma longa herb, on transforming growth factor (TGF)-beta1-induced CFs was investigated, and the underlying molecular mechanisms were examined. The expression levels of alpha-smooth muscle actin (SMA) stress fibers were investigated using western blotting and immunofluorescence in cultured neonatal rat CFs. Protein and mRNA expression levels of alpha-SMA and collagen type I (ColI) were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. In addition, the activation of Smad2 and p38 was examined using western blotting. Curcumin, SB431542 (a TGF-betaR-Smad2 inhibitor) and SB203580 (a p38 inhibitor) were used to inhibit the stimulation by TGF-beta1. The results demonstrated that the TGF-beta1-induced expression of alpha-SMA and ColI was suppressed by curcumin at the mRNA and protein levels, while SB431542 and SB203580 induced similar effects. Furthermore, phosphorylated Smad-2 and p38 were upregulated in TGF-beta1-induced CFs, and these effects were substantially inhibited by curcumin administration. In conclusion, the results of the present study demonstrated that treatment with curcumin effectively suppresses TGF-beta1 induced CF differentiation via Smad-2 and p38 signaling pathways. Thus, curcumin may be a potential therapeutic agent for the treatment of cardiac fibrosis. PMID- 26998028 TI - Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats. AB - Rolipram, a phosphodiesterase-4 inhibitor, can activate the cyclic adenosine monophosphate (cAMP)/cAMP-responsive element binding protein (CREB) pathway to facilitate functional recovery following ischemic stroke. However, to date, the effects of rolipram on angiogenesis and cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of rolipram on the angiogenesis and neuronal apoptosis following brain cerebral ischemia. Rat models of ischemic stroke were established following transient middle cerebral artery occlusion and rolipram was administered for three, seven and 14 days. The results were examined using behavioral tests, triphenyl tetrazolium chloride staining, immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to evaluate the effects of rolipram therapy on functional outcome, angiogenesis and apoptosis. Western blot analysis was used to show the phosphorylated- (p-)CREB protein level in the ischemic hemisphere. The rolipram treatment group exhibited a marked reduction in infarct size and modified neurological severity score compared with the vehicle group, and rolipram treatment significantly promoted the microvessel density in the ischemic boundary region and increased p-CREB protein levels in the ischemic hemisphere. Furthermore, a significant reduction in the number of TUNEL-positive cells was observed in the rolipram group compared with the vehicle group. These findings suggest that rolipram has the ability to attenuate cerebral ischemic injury, stimulate angiogenesis and reduce neuronal apoptosis though the cAMP/CREB pathway. PMID- 26998029 TI - Tirofiban combined with urokinase selective intra-arterial thrombolysis for the treatment of middle cerebral artery occlusion. AB - The aims of the present study were to establish a model of embolic stroke in rabbits and to evaluate the efficacy and safety of intra-arterially administered tirofiban combined with urokinase thrombolysis. The middle cerebral artery occlusion model (MCAO) of embolic stroke was established in New Zealand rabbits via an autologous clot. The model rabbits were allocated at random into four groups: Tirofiban group (T group), urokinase group (UK group), tirofiban and urokinase group (T + UK group) and the control group (C group). The recanalization rate, relative-apparent diffusion coefficient (rADC) and neurological function deficit score (NFDS) values were compared among the four groups. The recanalization rate, rADC and NFDS values were improved in the T + UK group compared with the other groups. In summary, the intra-arterial administration of tirofiban combined with urokinase thrombolysis was a more effective intervention in an MCAO model compared with intra-arterial urokinase alone, and may promote reperfusion and reduce infarct volume. PMID- 26998030 TI - Enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the medial prefrontal cortex is triggered by the expression of Fos protein in guinea pigs. AB - Eyelid conditioning, including delay eyelid conditioning and trace eyelid conditioning, has been used extensively to study neural structures and mechanisms of learning and memory as a form of associative learning. In the present study, microcurrent electrical stimulation was used to stimulate the medial prefrontal cortex (mPFC) to induce delay eyelid conditioning in guinea pigs. The acquisition rate and relative latency of the conditioned eyelid response (CR) and the startle eyelid response (SR) were analyzed. The mPFC sites in the guinea pigs were examined under a light microscope following Nissl staining. In addition, the expression of Fos protein in neurons was detected using immunohistochemistry and western blot analysis. The results indicated that the acquisition rates of CR and SR were increased significantly (P<0.05), whilst the relative latencies of CR and SR were decreased significantly (P<0.05). Lesions were observed in the mPFC regions in the training group when compared with the control group. In addition, immunohistochemistry and western blot analysis revealed that Fos expression was significantly increased in the training group when compared with the sham group for the control and resident-intruder test guinea pigs (P<0.05). Therefore, the enhancement of delay eyelid conditioning by microcurrent electrical stimulation of the mPFC in guinea pigs was triggered by the expression of Fos protein. The observations of the present study further expand the understanding of conditioned reflexes and may aid future investigations into the formation of eyelid conditioning and the mechanisms underlying the circuit in various conditions. PMID- 26998031 TI - Large hemorrhage due to venipuncture in the elbow of a patient with severe hemophilia: A case report and literature review. AB - Hemophilia A, which is the most common form of hemophilia, is caused by a deficiency of clotting factor VIII. The incidence of hemophilia A is 1:10,000 people worldwide. The most common complication associated with hemophilia A is bleeding into joints, predominantly the knees, ankles, and elbows, which may lead to destruction or osteoarthritis of the specific joint. Various degrees of disability may follow these initial or recurrent hemorrhages. Subsequent to improvements in medical management, patients with hemophilia A currently have a life expectancy similar to that of the normal population. However, the management of patients with hemophilia A remains a clinical challenge for various reasons, including the lack of reliable and cost-effective treatment, and the high risk of intra- or post-operative hemorrhages. Large hemorrhages due to the phlebotomizing of young patients are very rare. To the best of our knowledge, the present case is the first report regarding the occurrence of a large hemorrhage due to venipuncture in the elbow of a patient with hemophilia A, and discusses the pathogenesis, clinical manifestation, and the medico-chirurgical treatment of this patient. PMID- 26998032 TI - Plasma levels of D-dimer in a 5-year-old girl with systemic juvenile idiopathic arthritis: A case report and literature review. AB - The present study reported high levels of D-dimer associated with multiple joint pain in a 5-year-old patient with systemic juvenile idiopathic arthritis (JIA). While treatment with methotrexate (MTX), hydroxychloroquine and methylprednisolone was found to reduce the D-dimer level and alleviated joint pain, the fever was not effectively controlled. Addition of etanercept to the treatment regimen from week 2 resulted in a clinical remission. Following 4-6 months of therapy, the D-dimer level of the patient returned to the normal range, and symptoms of noticeable joint pain and fever were absent. A literature search showed that the levels of D-dimer may be associated with JIA disease severity, and can serve as a prognostic biomarker for JIA treatment. In conclusion, the present study demonstrated that, while MTX therapy effectively reduced D-dimer levels, addition of etanercept to the treatment regimen was required to achieve a long-lasting remission of clinical symptoms, including fever. PMID- 26998034 TI - Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers. AB - The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T-type calcium channel receptor subunits in the cochlea of 6 8-week-old C57BL/6J mice was evaluated using reverse transcription-quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T-type calcium channel blockers to protect the cochlear hair cells of 24-26-week-old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil-treated and benidipine-treated groups compared with the saline-treated group. The DPOAE amplitudes in the mibefradil-treated group were increased compared with those in the saline-treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine-treated group were increased compared with those in the saline-treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil-treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T-type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24-26-week-old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T-type calcium channel blocker; however, the IHCs were unaffected. PMID- 26998033 TI - Clinico-microbiological study and antibiotic resistance profile of mecA and ESBL gene prevalence in patients with diabetic foot infections. AB - Diabetic foot infections (DFIs) constitute a major complication of diabetes mellitus. DFIs contribute to the development of gangrene and non-traumatic lower extremity amputations with a lifetime risk of up to 25%. The aim of the present study was to identify the presence of neuropathy and determine the ulcer grade, microbial profile and phenotypic and genotypic prevalence of the methicillin resistance gene mecA and extended spectrum beta-lactamase (ESBL)-encoding genes in bacterial isolates of DFI in patients registered at the Pakistan Institute of Medical Sciences (Islamabad, Pakistan). The results indicated that 46/50 patients (92%), exhibited sensory neuropathy. The most common isolate was Staphylococcus aureus (25%), followed by Pseudomonas aeruginosa (P. aeruginosa; 18.18%), Escherichia coli (16.16%), Streptococcus species (spp.) (15.15%), Proteus spp. (15.15%), Enterococcus spp. (9%) and Klebsiella pneumoniae (K. pneumoniae; 3%). The prevalence of the mecA gene was found to be 88% phenotypically and 84% genotypically. K. pneumoniae was shown to have the highest percentage of ESBL producers with a prevalence of 66.7% by double disk synergy test, and 100% by the cefotaxime + clavulanic acid/ceftazidime + clavulanic acid combination disk test. P. aeruginosa and K. pneumoniae had the highest (100%) proportion of metallo beta lactamase producers as identified by the EDTA combination disk test. The overall prevalence of beta-lactamase (bla)-CTX-M, bla-CTX-M-15, bla-TEM, bla-OXA and bla SHV genes was found to be 76.9, 76.9, 75.0, 57.7 and 84.6%, respectively, in gram negative DFI isolates. The prevalence of mecA and ESBL-related genes was found to be alarmingly high in DFIs, since these genes are a major cause of antibiotic treatment failure. PMID- 26998035 TI - Protective effect of microRNA-138 against cerebral ischemia/reperfusion injury in rats. AB - MicroRNAs (miRs) serve a regulatory function in oxidative radical-mediated inflammation and apoptosis during ischemia/reperfusion (IR) injury. Lipocalin 2 (Lcn-2), a target protein of miR-138, is widely involved in the systemic response to IR injury. The aim of the present study was to investigate the association between miR-138 and Lcn-2 in a rat model of cerebral ischemia/reperfusion (CIR) injury and to verify the interaction between miR-138 and Lcn-2 in a PC12 cell model of hypoxia/reoxygenation injury. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expression levels of miR-138 and Lcn-2. Cell proliferation was determined by MTT assay. The results suggested that the expression of miR-138 was inversely correlated with the expression of Lcn-2 in the CIR rat model and the PC12 cells subjected to hypoxia and reoxygenation. The expression of Lcn-2 was inhibited by miR-138 mimics and enhanced by miR-138 inhibitors, thereby indicating that miR-138 functions as a negative regulator for Lcn-2 expression. This study provides an experimental basis for the further study of miR-138-based therapy for CIR injury. PMID- 26998036 TI - Puerarin and betahistine treatment of vertebrobasilar ischemia vertigo: A meta analysis of randomized controlled trials. AB - The present meta-analysis aimed to evaluate the effectiveness and safety of puerarin co-treatment with betahistine in treating vertebrobasilar ischemia (VBI) vertigo. A total of 6 medical databases were searched, identifying randomized controlled trials (RCTs) of VBI vertigo performed until August 2014 that investigated a combined treatment of puerarin with betahistine or with other conventional drugs. The quality of the literature was evaluated using the Cochrane Collaboration's tool for assessing risk of bias, and Rev Man 5.0 software was used for statistical analysis and evaluation. The present study included 7 RCTs, involving a total of 664 subjects, and revealed a statistically significant increase in efficacy between the control and the experimental group (odds ratio [OR], 4.99; 95% confidence interval [CI], 3.05 to 8.15). The average blood flow velocity within the vertebrobasilar arteries increased following treatment with puerarin and betahistine compared with that of the control groups (OR, 7.59; 95% CI, 6.19 to 9.00); however, no difference was detected between these groups in the average flow velocity within the left vertebral artery (OR, 6.17; 95% CI, 5.22 to 7.13). The frequency of adverse reactions in the experimental group was lower (OR, 0.75; 95% CI, 0.32 to 1.77) compared with the control group. Combined puerarin and betahistine regimens were more effective in treating VBI vertigo compared with other, conventional drugs; effectively alleviating the associated symptoms, including dizziness and increased average blood flow velocity within the vertebrobasilar arteries, without causing an increased number of serious side effects. However, the efficacy and safety of puerarin and betahistine use in treating VBI vertigo requires additional investigation. PMID- 26998037 TI - beta-catenin knockdown inhibits the proliferation of human glioma cells in vitro and in vivo. AB - beta-catenin is a crucial oncogene that is capable of regulating cancer progression. The aim of the present study was to clarify whether beta-catenin was associated with the proliferation and progress of glioma. In order to knockdown the expression of beta-catenin in human U251 glioma cells, three pairs of small interfering (si)RNA were designed and synthesized and the most effective siRNA was selected and used for silencing the endogenous beta-catenin, which was detected by western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferation was subsequently detected using a methylthiazolyl-tetrazolium bromide assay and the results demonstrated that knockdown of beta-catenin significantly inhibited the proliferation of U251 cells in a time- and dose-dependent manner (P<0.01). Cell apoptosis rate was analyzed using flow cytometry and Annexin V-fluorescein isothiocyanate/propidium iodide staining demonstrated that beta-catenin siRNA significantly increased the apoptosis of U251 cells (P<0.01). Furthermore, the results of an in vitro scratch assay demonstrated that beta-catenin silencing suppressed the proliferation of U251 cells, as compared with the control group (P<0.01). In vivo, beta-catenin expression levels in U251 cells were significantly inhibited (P<0.01) following beta-catenin short hairpin (sh)RNA lentiviral-vector transfection, as detected by western blot analysis and RT-qPCR. Tumorigenicity experiments demonstrated that beta-catenin inhibition significantly increased the survival rate of nude mice. The results of the present study demonstrated that knockdown of beta-catenin expression significantly inhibited the progression of human glioma cancer cells, in vitro and in vivo; thus suggesting that beta-catenin silencing may be a novel therapy for the treatment of human glioma. PMID- 26998038 TI - Adropin is associated with hyperhomocysteine and coronary atherosclerosis. AB - Homocysteine has been recognized as a risk factor for atherosclerosis and cardiovascular diseases. Adropin is a newly-identified energy homeostasis protein with a potential protective effect against coronary artery disease (CAD). This study attempted to measure the correlation between serum homocysteine and adropin levels in patients with CAD, and to ascertain how the two hormones could affect the severity of coronary atherosclerosis. A cohort of CAD patients who had undergone coronary angiography was prospectively recruited. The serum homocysteine and adropin levels of the patients were measured and the severity of coronary atherosclerosis was quantified with the SYNTAX score. The data were analyzed with a generalized structural equation model. In total, 170 consecutive patients were recruited with a mean serum homocysteine level of 15.9+/-8.3 umol/l, and 76 (44.7%) patients were identified as hyperhomocysteinemic with a serum homocysteine level >15 umol/l. Serum homocysteine level was found to be significantly negatively correlated with serum adropin level (r=-0.169, P=0.028). Patients with hyperhomocysteinemia had lower serum adropin levels and higher SYNTAX scores than patients without hyperhomocysteinemia. Further analysis with a generalized structural equation model showed that adropin was significantly associated with hyperhomocysteinemia (adjusted odds ratio: 0.95, 95% confidence interval: 0.93 to 0.98; P=0.002), which in turn was significantly associated with the SYNTAX score (coefficient: 4.71, 95% confidence interval: 1.39 to 8.03; P=0.005). In conclusion, the serum homocysteine level was inversely correlated with the serum adropin level in patients with CAD. A low serum adropin level was associated with hyperhomocysteinemia and more severe coronary atherosclerosis, as reflected by a higher SYNTAX score. PMID- 26998039 TI - Rosiglitazone ameliorates astrocyte over-activation and inflammatory cytokine release induced by global cerebral ischemia/reperfusion. AB - Global cerebral ischemia (GCI) is a leading cause of mortality worldwide and remains the primary cause of long-term neurological disability. Astrocyte over activation and extensive neuron loss in the ischemic brain are the characteristic pathological features of cerebral ischemia. Rosiglitazone (RSG) is a peroxisome proliferating activating receptor-gamma agonist known for its anti-inflammatory activity. Previous studies have suggested that RSG is able to exert neuroprotection in numerous acute and chronic brain injury models. However, whether RSG treatment is involved in astrocyte over-activation and inflammatory reaction in the cortex remains unclear. The aim of the present study was to investigate whether RSG treatment improved functional impairment induced following GCI and protected against cortex neuron loss, and to elucidate the potential mechanisms underlying these functions. Rats were randomly divided into three groups: Sham-operated, GCI and RSG treatment groups. The RSG treatment group was treated with 2 mg/kg RSG immediately following GCI. The results demonstrated that RSG treatment significantly reduced infarct volume and neuron survival rates in addition to increasing function recovery. Furthermore, these results correlate with a reduction in astrocyte over-activation and inflammatory cytokines in the rat cortex. However, no significant changes in glutamate transporter-1 expression levels were observed following RSG treatment compared with the GCI rats. The results of this investigation provide in vivo evidence that RSG significantly protected rats against ischemia-reperfusion-induced brain injury. In addition, RSG may exert neuroprotective effects by inhibiting astrocyte over-activation, and thereby reducing the levels of inflammatory cytokines in the GCI-injured brain. All data revealed that RSG may be a potential neuroprotective agent for cerebral ischemia. PMID- 26998040 TI - Peripheral T-lymphocyte and natural killer cell population imbalance is associated with septic encephalopathy in patients with severe sepsis. AB - Septic encephalopathy (SE) is a diffuse cerebral dysfunction resulting from a systemic inflammatory response, and is associated with an increased risk of mortality. The pathogenesis of SE is complex and multifactorial, but unregulated immune imbalance may be an important factor. The current retrospective study examined the clinical data of 86 patients with severe sepsis who were admitted to the Intensive Care Unit at Zhongshan Hospital, Xiamen University (Xiamen, China) from January, 2014 to January, 2015. The patients were assigned to SE and non-SE patient groups according to the presence or absence of SE. The proportion of T lymphocyte subsets and natural killer (NK) cells in the immune cell population, representing the function of the immune system, were analyzed for their association with SE and compared with other clinical predictors and biomarkers. The incidence of SE in the patients was 39.5%, and this group demonstrated higher mortality rates (38 vs. 10% in non-SE patients; P=0.001). Univariate analysis revealed that the SE patients reported a lower percentage of cluster of differentiation 4+(CD4+) T-lymphocytes (51.67+/-7.12 vs. 60.72+/-3.70% in non-SE patients; P<0.01), a lower CD4+/cluster of differentiation 8+(CD8+) ratio (1.59+/ 0.32 vs. 1.85+/-0.26% in non-SE patients; P<0.01) and a higher percentage of NK cells (11.80+/-1.44 vs. 9.19+/-2.36% in non-SE patients; P<0.01). Using a binary logistic regression model, the Acute Physiology and Chronic Health Evaluation II score and the percentage of CD4+ T-lymphocytes were demonstrated to be independently associated with SE (respectively, P=0.012 and OR, 4.763; P=0.005 and OR, 0.810). An area under the curve analysis of a receiver operating characteristic curve of the two indicators revealed that these were equally powerful measures in prediction of SE (Z=1.247, P>0.05). The present results confirm that SE leads to higher mortality in patients with severe sepsis, and demonstrate that immune imbalance is important in the development of SE. The proportion of CD4+ T-lymphocytes present were revealed in the current study to be a powerful predictor of SE in patients with severe sepsis. PMID- 26998041 TI - Tanshinone IIA enhances chemosensitivity of colon cancer cells by suppressing nuclear factor-kappaB. AB - The aim of the present study was to investigate the effect and molecular mechanism of tanshinone IIA (TSA) on colon cancer cells. Cell viability was determined using Cell Counting kit-8 assay and the results demonstrated that TSA treatment significantly decreased the cell viability of HCT1116 and COLO205 cells in a dose-dependent manner. TSA treatment also sensitized HCT1116 and COLO205 cells to fluorouracil therapy in a concentration-dependent manner. Western blotting was performed in order to investigate the molecular mechanisms of TSA action and determine the level of phosporylated p65 and nuclear factor-kappaB (NF kappaB)-regulated genes, including vascular endothelial growth factor (VEGF), c Myc, cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2). The results revealed that TSA treatment greatly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-kappaB activation by TSA treatment. TSA also decreased the expression levels of VEGF, c-Myc, COX-2 and Bcl-2. Furthermore, the inhibition of NF-kappaB activation with the specific inhibitor, pyrrolidine dithiocarbamate, increased the induction of cell death and chemosensitization effect of TSA in colon cancer cells. In conclusion, these results suggest that TSA induces cell death and chemosensitizes colon cancer cells through the suppression of NF-kappaB signaling. PMID- 26998042 TI - Selective laser trabeculoplasty in treating post-trabeculectomy advanced primary open-angle glaucoma. AB - The aim of this study was to investigate the safety and efficacy of selective laser trabeculoplasty (SLT) treatment of patients with primary open-angle glaucoma (POAG) who could not obtain target intraocular pressure (IOP) through post-trabeculectomy medication. Sixteen patients with POAG (18 eyes), who could not obtain target IOP following medication and surgery, were treated with 360 degrees SLT. The IOP, anterior chamber inflammation, and daytime and long-term IOP fluctuations before and 2 h, 1 day, 7 days, 1 month, 3 months, 6 months and 9 months after SLT were documented. SLT treatment success was defined as >20% IOP reduction compared with the baseline IOP at 6 and 9 months after the laser treatment date. Prior to SLT, the patients were administered different types (average, 2.8+/-0.8) of anti-glaucoma drugs and had an average IOP of 21.3+/-3.4 mmHg. Following SLT, the average IOP decreased to 16.2+/-3.0 mmHg and the success rate was 77.7%. The pre-SLT daytime IOP fluctuation was 4.1+/-1.4 mmHg, which decreased to 2.6+/-1.1 mmHg following the laser treatment (P<0.05). In conclusion, this study demonstrated that SLT could reduce the IOP in post trabeculectomy patients with POAG, and reduce the daytime IOP fluctuations. PMID- 26998044 TI - Sputum endothelin-1 level is associated with active pulmonary tuberculosis and effectiveness of anti-tuberculosis chemotherapy. AB - Pulmonary tuberculosis (TB) is a major global health problem. Endothelin (ET)-1 is an important pro-inflammatory factor in the airways, which acts as a chemoattractant and an upregulator of other inflammatory mediators. In the present study, the association of the sputum ET-1 level with active pulmonary TB and the effectiveness of anti-TB chemotherapy was explored for the first time. A total of 56 newly diagnosed patients with active pulmonary TB, 56 age- and gender matched TB-free controls, and 43 subjects with latent TB were recruited to the study. Patients in the active TB group received standard anti-TB chemotherapy. Sputum samples were collected from all study subjects at baseline (day 0) and on days 1, 2, 4, 6, 10 and 14 of treatment for the active TB group and the ET-1 level was determined by enzyme-linked immunosorbent assay. The sputum ET-1 level in the active TB group was significantly higher than those in the latent TB and the non-TB groups at baseline. Following adjustment for confounders such as age, gender, severity of clinical presentation, plasma ET-1 level and comorbidities that might affect the sputum ET-1 level, multivariate logistic regression analysis revealed that sputum ET-1 level was an independent indicator for active pulmonary TB. In the active TB group during anti-TB chemotherapy, decrements in the sputum ET-1 level were in significant correlation with decrements in the number of colony-forming units and increments in the time to positivity in a Mycobacteria Growth Indicator Tube assay. In conclusion, this study indicates that an elevated sputum ET-1 level is an independent indicator of active pulmonary TB and suggests that decrements in the sputum ET-1 level could reflect the effectiveness of anti-TB chemotherapy. PMID- 26998043 TI - Metformin reduces the expression of NADPH oxidase and increases the expression of antioxidative enzymes in human monocytes/macrophages cultured in vitro. AB - The treatment of diabetes and its complications is a key challenge for healthcare professionals. Accelerated atherosclerosis is associated with progressive diabetes, and it has been indicated that macrophages serve a crucial function in this process. Currently, the first-line treatment of diabetes is based on metformin, which is an inducer of AMP-activated protein kinase (AMPK) and belongs to the biguanide class of pharmaceuticals. It has been previously demonstrated that metformin exhibits more than just hypoglycemic effects. Therefore, the aim of the present study was to investigate the in vitro impact of metformin on cell viability and the expression levels of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (p22phox), a major enzyme in reactive oxygen species generation, and the three antioxidative enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in monocytes/macrophages derived from 10 healthy volunteers. The effects of metformin were observed in the presence or absence of lipopolysaccharide (LPS), which was administered to induce oxidative stress. Furthermore, certain cells were treated with compound C, an inhibitor of AMPK, in order to determine the mechanistic role played by AMPK in the oxidative changes in the macrophages. Cell viability was evaluated using trypan blue and MTT assays. The mRNA and protein expression levels of p22phox and the various antioxidative enzymes were determined using polymerase chain reaction and western blot analysis, respectively. The results indicated that metformin, predominantly in LPS-pretreated monocytes/macrophages, reduced the expression levels of p22phox and increased those of SOD and GPx, but had only a minor effect on CAT levels. Therefore, metformin appears to alter the oxidative status of macrophages toward increasingly antioxidative activity, which may account for the pleiotropic effects observed during metformin treatment. PMID- 26998046 TI - Total flavonoids of Hedyotis diffusa Willd inhibit inflammatory responses in LPS activated macrophages via suppression of the NF-kappaB and MAPK signaling pathways. AB - Nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways play a central role in inflammatory responses. Total flavonoids of Hedyotis diffusa Willd (TFHDW) are active compounds derived from Hedyotis diffusa Willd, which has been long used in Chinese traditional medicine for the treatment of various inflammatory diseases, including ulcerative colitis and bronchitis; however, the precise mechanisms underlying the effects of TFHDW are largely unknown. In the present study, the anti-inflammatory effect of TFHDW was evaluated and the underlying molecular mechanisms were investigated in an in vitro inflammatory model comprising lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The results indicated that TFHDW inhibited the inflammatory response as it significantly reduced the LPS-induced expression of pro-inflammatory nitric oxide, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-1beta in a concentration-dependent manner, without causing cytotoxicity. In addition, the mRNA expression of inducible nitric oxide synthase, TNF-alpha, IL-6 and IL-1beta was suppressed by treatment with TFHDW in LPS-stimulated RAW 264.7 cells. Moreover, TFHDW treatment significantly inhibited the LPS-induced activation of NF-kappaB via the suppression of inhibitor of kappaB (IkappaB) phosphorylation, and reduced the phosphorylation of MAPK signaling molecules (p38, c-Jun N terminal protein kinase and extracellular signal-regulated kinase 1/2), which resulted in the inhibition of cytokine expression. These findings suggest that TFHDW exerted anti-inflammatory activity via suppression of the NF-kappaB and MAPK signaling pathways. PMID- 26998045 TI - Anti-inflammatory potential of total saponins derived from the roots of Panax ginseng in lipopolysaccharide-activated RAW 264.7 macrophages. AB - Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a widely known traditional medicine that has been utilized throughout Asia for several thousand years. Ginseng saponins exert various important pharmacological effects regarding the control of a number of diseases. The aim of the present study was to identify the anti-inflammatory effects of total saponins extracted from ginseng (TSG) on lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages. The inhibitory effects of TSG on LPS-induced nitric oxide (NO) production and LPS-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) protein expression were determined by measuring the levels of nitrite and enzyme-linked immunosorbent assays, respectively. Furthermore, the effects of TSG on the mRNA expression levels and localizations of inducible NO synthase (iNOS), IL-1beta and TNF-alpha, and their upstream signaling proteins, including nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs), were investigated by reverse transcription-polymerase chain reaction and western blotting, respectively. Following stimulation with LPS, elevated levels of NO production were detected in RAW 264.7 cells; however, TSG pretreatment significantly inhibited the production of NO (P<0.05), by suppressing the expression of iNOS. In addition, LPS-stimulated TNF-alpha and IL-1beta production was significantly reduced by TSG (P<0.05). In the LPS-stimulated RAW 264.7 cells, NF-kappaB was translocated from the cytosol to the nucleus, whilst TSG pretreatment induced the sequestration of NF-kappaB in the cytosol by inhibiting inhibitor of kappaB degradation. TSG also contributed to downregulation of MAPKs in LPS-stimulated RAW 264.7 cells. These results suggested that TSG may exert anti-inflammatory activity, and that TSG may be considered a potential therapeutic for the treatment of inflammatory diseases associated with macrophage activation. PMID- 26998047 TI - Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial. AB - The aim of the present study was to investigate the efficacy of L-carnitine therapy on the occurrence and prognosis of respiratory distress syndrome (RDS). A single blind, randomized controlled trial study was conducted on 130 infants with gestational ages of 28-36 weeks. Infants were assigned to experimental groups (groups 1 and 2) and control groups (groups 3 and 4). Groups 1 and 3 consisted of infants with RDS, and groups 2 and 4 groups were composed of infants without RDS. The experimental groups were treated with carnitine. No statistically significant differences in serum carnitine levels were detected between the study and the control groups on day 1 of treatment (P=0.06). However, on day 7 of treatment, serum carnitine levels in the experimental groups were significantly increased (P=0.02), as compared with the control groups. The surfactant requirement value, which is how many rounds of surfactant therapy were required, was 1.56+/-0.97 in group 1, and 2.12+/-0.99 in group 3 (P<0.001). The mean duration of mechanical ventilation required was 3.04+/-3.60 days in group 1, and 4.73+/-5.63 days in group 3 (P<0.001). The present results indicate that carnitine supplementation in premature infants with RDS may help to increase carnitine levels, thus decreasing the duration of mechanical ventilation and surfactant requirement. PMID- 26998049 TI - Total glucosides of peony ameliorates Sjogren's syndrome by affecting Th1/Th2 cytokine balance. AB - The present study aimed to investigate the molecular mechanisms underlying the effects of total glucosides of peony (TGP) in the treatment of Sjogren's syndrome (SS). A total of 40 mice with SS were evenly assigned into four groups, including: Control group; TGP group, receiving 1 mg TGP daily; hydroxychloroquine (HCQ) group, receiving 0.25 mg HCQ daily; and a combined group, receiving 1 mg TGP and 0.25 mg HCQ daily. After 8 weeks, quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay were used to detect the levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), Fas and FasL in each group of mice. In addition, immunohistochemical analysis was used to determine the expression levels of IFN-gamma and IL-4. IFN-gamma, IL-4, Fas and FasL levels were significantly increased in the control group compared with the other three groups (P<0.05). Furthermore, the expression levels of these factors were reduced in the combined group in comparison with the HCQ group (P<0.05). The ratios of IFN-gamma to IL-4 were decreased in the TGP and combined groups compared with the control group (P<0.05). The present results indicate that TGP ameliorates SS by affecting the Th1/Th2 cytokine balance and decreasing the expression levels of IFN-gamma, IL-4, Fas and FasL. Therefore, TGP may represent a potential novel therapeutic agent for the treatment of SS. PMID- 26998048 TI - Beneficial effects of intravenous dexmedetomidine on cognitive function and cerebral injury following a carotid endarterectomy. AB - The present study aimed to investigate the effects of dexmedetomidine (DEX) on cognition following a carotid endarterectomy (CEA). In addition, the neuroprotective effects of DEX against ischemia-reperfusion injury during CEA were analyzed. Patients due to undergo elective CEA under general anesthesia were randomly assigned to either the DEX-treated group (group D; n=25) or the control group (group C; n=25). Patients in group D were treated with 0.3 ug/kg DEX pre CEA, followed by 0.3 ug/kg/h DEX intraoperatively up to 30 min prior to the completion of surgery, and the patients in group C received an equal volume of normal saline. Cognitive function was assessed prior to CEA (T0), and at 24, 48, and 72 h, 7 days and 1 month post-surgery (T1-5, respectively), using the Mini Mental State Examination (MMSE). Blood samples were drawn from the ipsilateral jugular bulb of all patients at 20 min prior to anesthesia (t0), and at 10 min following tracheal intubation, 15 min following clamping and unclamping of the carotid artery, and at 6 and 24 h postoperatively (t1-5, respectively). The protein expression levels of markers of cerebral ischemia and injury, namely S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE), and the concentration of the oxidative stress marker malondialdehyde (MDA), were analyzed. Patients in group D exhibited elevated MMSE scores at T2 and T3 post CEA, as compared with group C. Furthermore, the protein expression level of S100B and the concentration of MDA in the jugular bulb of group D patients were markedly decreased compared with those in group C at t3-5 and t3, respectively. The results of the present study suggested that DEX was able to enhance the recovery of cognition following CEA, and this was associated with decreased cerebral damage and antioxidative effects. PMID- 26998050 TI - SNPs in the aryl hydrocarbon receptor-interacting protein gene associated with sporadic non-functioning pituitary adenoma. AB - Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have previously been associated with a predisposition to pituitary adenomas. However, to the best of our knowledge, mutations in AIP that relate specifically to sporadic non-functioning pituitary adenomas (NFPAs) have yet to be reported. Therefore, the present study aimed to identify single nucleotide polymorphisms (SNPs) in the AIP gene that may be associated with NFPAs. Peripheral blood samples and the entire coding sequence of the AIP gene from 56 patients with NFPAs and 56 controls were analyzed in triplicate. Of the 56 patients with NFPAs, 9 patients (16.1%) were identified as harboring five different SNPs, although no germline mutations in the AIP gene were detected in any of the patients. Three different SNPs (7051C>T, 8012G>C and 8020G>C) were identified in exons 4 and 6 in 3 different patients (each in 1 patient). Two different SNPs (7318C>A and 7886A>G) were identified in exons 5 and 6, respectively, in 6 different patients (each in 3 patients). No SNPs or germline mutations in the AIP gene were identified in the controls. The results of the present study suggested that mutations in the AIP gene might not have an important role in the tumorigenesis of NFPAs. However, further studies are required in order to investigate potential molecular and genetic mechanisms that may underlie the involvement of AIP in NFPA. PMID- 26998051 TI - Serum tau protein as a potential biomarker in the assessment of traumatic brain injury. AB - Traumatic brain injury (TBI) is the leading cause of mortality and disabilities among all trauma cases. Following TBI, damage to axons results in tau protein hyperphosphorylation leading to microtubule instability and tau-mediated neurodegeneration. In addition, tau protein is proteolytically cleaved and is able to access the cerebrospinal fluid (CSF) and serum; thus, this protein may serve as a potential biomarker in the diagnosis of injury severity and outcome prediction. Although a limited number of studies have investigated the CSF tau protein levels after TBI, the data are divergent and conflicting, and investigations into the serum tau protein levels have yet to be conducted. Therefore, the present study aimed to examine the serum tau protein levels in the full spectrum of TBI patients on days 0-14 after TBI, using an enzyme-linked immunosorbent assay. The protein levels were compared to the initial Glasgow Coma Score (GCS) and the Extended Glasgow Outcome Scale (GOS-E), which are used to represent the injury severity and patient outcome, respectively. In total, 56 patients, including 20 patients with mild TBI (GCS, 13-15), 19 patients with moderate TBI (GCS, 9-12) and 17 patients with severe TBI (GCS, 3-8), were included in the current study. The outcome was assessed 1 year after the injury and patients were classified into the good outcome (40 cases; GOS-E, 5-8) and poor outcome groups (16 cases; GOS-E, 1-4). The results indicated that serum tau protein levels increased soon after TBI and reached a peak value at ~2 days after the injury. The serum tau protein levels were significantly higher in the severe TBI group compared with those in the mild and moderate TBI groups (P<0.0001). Univariate analysis indicated that poor outcome was significantly associated with higher serum tau protein levels on day 2 (P<0.0001). A receiver operating characteristic curve demonstrated that a tau protein level of >116.04 pg/ml on day 2 resulted in a 93.75% sensitivity and 92.50% specificity for predicting a poor outcome. Furthermore, a tau protein level of >372.1 pg/ml on day 2 yielded 100% sensitivity and 83.33% specificity for 1 year mortality in the severe TBI group. In conclusion, the present study suggests that serum tau protein may serve as a potential biomarker for evaluating the injury severity and predicting the outcome of TBI patients. PMID- 26998052 TI - Epithelial-mesenchymal transition in glioblastoma progression. AB - Epithelial-mesenchymal transition (EMT) is a reversible biological process that occurs in epithelial cells. EMT ultimately leads to the acquisition of a mesenchymal phenotype, characterized by increased cell motility and resistance to genotoxic agents. These processes mostly overlap with the acquirement of stem cell properties in differentiated tumor cells. With regard to gliomas, the clinical picture is heterogeneous, even within the same grades and histological categories of the disease. Furthermore, the areas of invasion and responses to radiochemotherapy are markedly different among cases, and occasionally even in the same patient. Such phenotypic diversity in glioma tissues may be caused by various microenvironmental factors, as well as intrinsic genetic alterations. The current review focuses on the EMT-inducing factors that are present in gliomas; these typically vary from those observed in epithelial cancers, as no basement membrane is present. Furthermore, the most important cell-cell contact factor, E cadherin, is rarely expressed in gliomas. The microenvironment that induces EMT in gliomas is characterized by hypoxia and the enrichment of myeloid cells following stimulation by transforming growth factor-beta. Anti-vascular endothelial growth factor therapy, including the use of bevacizumab, may be a suitable candidate to modulate the glioma microenvironment. PMID- 26998054 TI - Evidence-based treatment of patients with rectal cancer. AB - Rectal cancer is a worldwide disease whose incidence has increased significantly. Evidence-based medicine is a category of medicine that optimizes decision making by using evidence from well-designed and conducted research. Evidence-based medicine can be used to formulate a reasonable treatment plan for newly diagnosed rectal cancer patients. The current review focuses on the application of evidence based treatment on patients with rectal cancer. The relationship between perioperative blood transfusion and recurrence of rectal cancer after surgery, the selection between minimally invasive laparoscopic surgery and traditional laparotomy, choice of chemotherapy for patients with rectal cancer prior to surgery, selection between stapled and hand-sewn methods for colorectal anastomosis during rectal cancer resection, and selection between temporary ileostomy and colostomy during the surgery were addressed. Laparoscopy is considered to have more advantages but is time-consuming and has high medical costs. In addition, laparoscopic rectal cancer radical resection is preferred to open surgery. In radical resection surgery, use of a stapling device for anastomosis can reduce postoperative anastomotic fistula, although patients should be informed of possible anastomotic stenosis. PMID- 26998053 TI - Novel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications. AB - Long non-protein-coding RNAs (lncRNAs) are emerging as important gene expression regulators that are linked to various biological processes at the post transcriptional and transcriptional levels. lncRNAs are known to be important in cell proliferation, cell differentiation, apoptosis and metastasis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), a novel lncRNA, is highly conserved amongst mammals. In addition, it has been considered to act as an oncogene, depending on the tumor system. An increasing number of studies have indicated that MALAT-1 may be detected in certain types of human tumors, including lung and bladder cancer and hepatocellular carcinoma. MALAT-1 silencing may be an effective therapeutic approach against tumors. The present study reviews the current knowledge on the functional role of MALAT-1 in the control of various cancers. PMID- 26998056 TI - Circulating microRNA profile predicts disease progression in patients receiving second-line treatment of lapatinib and capecitabine for metastatic pancreatic cancer. AB - Patients exhibiting pancreatic cancer possess poor rates of survival. Therefore, the identification of a biomarker that can be measured non-invasively and be used to predict patient outcomes is required for the successful treatment of pancreatic cancer. The present study evaluated serum microRNA (miRNA/miR) profiles in patients exhibiting pancreatic cancer, who were treated with lapatinib and capecitabine in a phase II trial. Serum samples were collected for the measurement of a panel of miRNAs (miR-21, miR-210, miR-221 and miR-7) associated with the epidermal growth factor receptor (EGFR)1 and human epidermal growth factor receptor (HER)2 pathways. Preclinically, human pancreatic cancer PANC-1, MIA PaCa-2 and BXCP-3 cell lines were utilized for miRNA and drug resistance studies. In total, 6/17 patients treated experienced disease progression following 2 cycles of treatment [non-responders (NRS)], while another 6/17 patients exhibited a stable disease state and received >4 cycles of treatment [responders (RS); range, 4-22 cycles]. Five patients withdrew from the study due to severe toxicity or mortality. The mean overall survival time was 6.5 vs. 10.4 months for NRS and RS, respectively. Significant upregulation of serum miRNAs at earlier time points (3-6 weeks) was observed in NRS. miRNA levels increased with cancer progression, and lapatinib and 5-fluorouracil (5-FU; the active form of capecitabine) treatment increased the miRNA levels (specifically miR-210 and miR-221) in the treatment-resistant pancreatic cancer PANC-1 and MIA PaCa-2 cell lines. However, lapatinib and 5-FU treatment did not increase the miRNA levels in the treatment-sensitive BXPC-3 cell line. Inhibition of miR-221 increased the sensitivity of the PANC-1 cells to treatment. In conclusion, an increase in specific serum miRNAs was associated with resistance to lapatinib and capecitabine treatment. Additional investigation is required with regard to the application of the miRNA panel investigated in the present study as a potential predictor of patient responses to anti-EGFR/HER2 treatment. PMID- 26998057 TI - Assessment of ALK gene fusions in lung cancer using the differential expression and exon integrity methods. AB - Anaplastic lymphoma kinase (ALK) gene fusion is a driving mutation underlying the development of non-small cell lung cancer (NSCLC). Accurate detection of ALK fusion is critical for the use of ALK inhibitors in the treatment of NSCLC. Commonly utilized methods for ALK detection include fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). However, these methods are time-consuming and costly. In the present study, a method for assessing ALK gene fusion based on the differential expression levels of the ALK kinase and non kinase domains was developed and evaluated, with the aim of providing a convenient and reliable method for the detection of ALK fusion. In addition, another method was established to determine the integrity of exons 19-20 and 20 21 of ALK, two genomic loci that are typically broken in ALK fusions. These novel methods were applied to detect ALK fusion in 100 NSCLC patients, and were compared with IHC and FISH methods. The novel methods developed in the present study successfully detected ALK fusions in 10 samples. The concordances between the novel methods and IHC and FISH were 100%. Furthermore, the differential expression method was able to detect ALK fusions in cell-free urine samples, which was advantageous over FISH and IHC. The novel methods developed in the present study are cost-effective and easy to perform, and may provide simple and convenient techniques for the clinical assessment of ALK fusions, facilitating the use of targeted therapy for NSCLC. PMID- 26998058 TI - Transcervical excision of intramasseteric cavernous hemangioma: A case report. AB - Intramuscular hemangiomas (IMHs) of the masseter muscle are extremely rare in the head and neck region and, thus, are often misdiagnosed as parotid tumors prior to surgery. Excisional resection remains the standard treatment for IMH. Since these tumors are located on the proximal side of the facial nerve, it is important to preserve the facial nerve during surgery. This study reports the case of a 57 year-old male who presented with a progressive tender swelling on the right side of the face, which had been present for >6 months. Computed tomography of the neck revealed a heterogeneous highly-vascularized mass located in the superficial layer of the masseter muscle. The patient subsequently underwent surgical resection via a collar incision, and pathological examination revealed a cavernous IMH. During the one-year follow-up period, the patient exhibited a good prognosis, and one-year magnetic resonance imaging revealed no local recurrence. PMID- 26998055 TI - Herpes and polyoma family viruses in thyroid cancer. AB - Thyroid cancer is considered the most common malignancy that affects the endocrine system. Generally, thyroid cancer derives from follicular epithelial cells, and thyroid cancer is divided into well-differentiated papillary (80% of cases) and follicular (15% of cases) carcinoma. Follicular thyroid cancer is further divided into the conventional and oncocytic (Hurthle cell) type, poorly differentiated carcinoma and anaplastic carcinoma. Both poorly differentiated and anaplastic carcinoma can arise either de novo, or secondarily from papillary and follicular thyroid cancer. The incidence of thyroid cancer has significantly increased for both males and females of all ages, particularly for females between 55-64 years of age, from 1999 through 2008. The increased rates refer to tumors of all stages, though they were mostly noted in localized disease. Recently, viruses have been implicated in the direct regulation of epithelial mesenchymal transition (EMT) and the development of metastases. More specifically, Epstein-Barr virus (EBV) proteins may potentially lead to the development of metastasis through the regulation of the metastasis suppressor, Nm23, and the control of Twist expression. The significant enhancement of the metastatic potential, through the induction of angiogenesis and changes to the tumor microenvironment, subsequent to viral infection, has been documented, while EMT also contributes to cancer cell permissiveness to viruses. A number of viruses have been identified to be associated with carcinogenesis, and these include lymphotropic herpesviruses, namely EBV and Kaposi's sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus type 8 (HHV8)]; two hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV); human papillomaviruses (HPVs); human T cell lymphoma virus (HTLV); and a new polyomavirus, Merkel cell polyomavirus identified in 2008. In this review, we examined the association between thyroid cancer and two oncogenic virus families, the herpes and polyoma family viruses, and we discuss their potential role as causative agents in thyroid carcinogenesis. PMID- 26998059 TI - Initial evidence for Sec62 as a prognostic marker in advanced head and neck squamous cell carcinoma. AB - Head and neck squamous cell carcinoma (HNSCC) is a malignancy with an increasing incidence. To aid with the selection of the most appropriate therapy, biomarkers have become a specific research focus. Sec62 is involved in endoplasmic reticulum stress tolerance and cell migration, and has been identified as a novel prognostic marker for non-small cell lung cancer. In addition, Sec62 may be a promising candidate in HNSCC. Pretreatment biopsies of 35 patients with locally advanced HNSCC, who were treated with definitive chemoradiation therapy without prior surgery, were examined for the expression of Sec62 protein, as well as the expression of epidermal growth factor receptor (EGFR), p16 and survivin proteins. Immunohistological results were correlated with patient overall survival (OS) and progression-free survival (PFS) times. In the present patient cohort, 12/35 cases (34%) demonstrated strong and 8/35 cases (23%) moderate Sec62 staining intensity. Additionally, in 11/35 cases (31%), weak staining was observed, and only 4/35 cases (11%) were Sec62-negative. Notably, a high Sec62 protein level was associated with a significantly poorer OS and PFS (P=0.020 and P=0.028, respectively). Furthermore, higher nuclear survivin expression showed a weak trend for poorer OS rate (P=0.079), whilst neither cytoplasmic survivin, EGFR nor p16 influenced OS or PFS significantly. The present study indicated that Sec62 is a promising prognostic marker for HNSCC. Increased Sec62 protein expression may indicate a poorer prognosis in advanced HNSCC. As the present study was focused on patients treated by chemoradiation therapy, further studies with larger patient cohorts and alternative treatment approaches are required in order to define the prognostic value of Sec62 in HNSCC. PMID- 26998060 TI - Small cell carcinoma of the rectum: A report of imaging results from four cases. AB - Small cell carcinoma of the rectum is extremely rare. The present study aimed to improve the recognition of computed tomography (CT) and magnetic resonance imaging (MRI) features observed in patients with small cell carcinoma of the rectum. A total of 4 cases of patients with histologically confirmed small cell carcinoma of the rectum were retrospectively reviewed. The imaging features assessed consisted of the thickening of the rectal wall, local tumor invasion, CT density, MRI signal intensity, lesion texture, contrast enhancement characteristics, lymphadenopathy and distant metastasis. All 4 patients displayed ring-like rectal wall thickening and hypodensity in comparison to the gluteus muscles on non-enhanced CT images. MRI demonstrated isointensity on T1-weighted images and hyperintensity on T2-weighted images. Thickening of the left wall of the rectum with patchy low attenuation and the presence of an exophytic mass was observed in 1 patient. Local tumor invasion was observed in the perirectal fat spaces of 4 patients, in the prostate gland and seminal vesicle of 1 patient, and in the left seminal vesicle of 1 patient. Heterogeneous attenuation was exhibited on non-enhanced CT images in 3 lesions, and 1 lesion exhibited heterogeneous intensity on non-enhanced MRI images. All the lesions observed demonstrated strong enhancement following contrast imaging. Lymphadenopathy was observed in 4 patients, liver metastasis in 3 patients, pulmonary metastasis in 2 patients and multiple bone metastases in 1 patient. Overall, small cell carcinoma of the rectum appeared to be more likely to metastasize to the liver, pulmonary, lymph nodes and bone. Distinguishing features of small cell carcinoma of the rectum were noted as a thickening rectal wall, the presence of soft-tissue tumors, local tumor invasion, lymphadenopathy and distant metastases. Pre-operative CT and MRI are required as an aid in selecting the correct treatment plan and for the prognosis assessment of patients. PMID- 26998061 TI - Clinical significance of midkine expression in sporadic desmoid tumors. AB - The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin associated protein) beta1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of beta-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed beta-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P<0.009) were independent prognostic factors of tumor recurrence. In conclusion, the present results suggest that the tumor site and midkine expression may be predictive markers for the recurrence of sporadic desmoid tumors. PMID- 26998062 TI - A novel AKT inhibitor, AZD5363, inhibits phosphorylation of AKT downstream molecules, and activates phosphorylation of mTOR and SMG-1 dependent on the liver cancer cell type. AB - Due to frequent phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway dysregulation, AKT is typically accepted as a promising anticancer therapeutic target. mTOR, in particular, represents a suitable therapeutic target for hepatocellular carcinoma, whilst suppressor with morphogenetic effect on genitalia family member-1 (SMG-1) is believed to serve a potential tumor suppressor role in human cancer. Despite SMG-1 and mTOR belonging to the same PI3K-related kinase family, the interactions between them are not yet fully understood. In the present study, a novel pyrrolopyrimidine-derived compound, AZD5363, was observed to suppress proliferation in liver cancer Hep-G2 and Huh-7 cells by inhibiting the phosphorylation of downstream molecules in the AKT signal pathway, in a dose- and time-dependent manner. AZD5363 activated the phosphorylation of mTOR, dependent on the liver cancer cell type, as it may have differing effects in various liver cancer cell lines. Additionally, AZD5363 also activated SMG-1 within the same liver cancer cells types, which subsequently activated the phosphorylation of mTOR. In conclusion, the present study indicates that AZD5363 inhibited phosphorylation of AKT downstream molecules, and activated phosphorylation of mTOR and SMG-1, dependent on the liver cancer type. PMID- 26998063 TI - 20(S)-Protopanaxadiol saponins inhibit SKOV3 cell migration. AB - While the anti-tumor actions of ginsenosides from Panax notoginseng are well studied, the anti-proliferative activity of 20(S)-protopanaxadiol saponins (PDS) in Sanchi ginseng on human ovarian cancer has not been reported, nor has its effect on migration of SKOV3 cells been investigated. In the present study, a wound-healing assay indicated that PDS inhibited the migration of SKOV3 cells, and a MatrigelTM tube formation assay demonstrated the presence of inhibitory tube-structures following treatment with PDS. To date, there are no previous reports on the regulation of osteopontin (OPN), a glycophosphoprotein cytokine frequently expressed in ovarian carcinoma effusions by PDS. A reduction in the expression of OPN following PDS-treatment was observed using immunohistochemical and western blot experiments. These results suggest that PDS may be useful in the search for a potential ovarian cancer treatment. PMID- 26998064 TI - Typical CT and MRI signs of hepatic epithelioid hemangioendothelioma. AB - To investigate the typical magnetic resonance imaging (MRI) and computed tomography (CT) features of hepatic epithelioid hemangioendothelioma (HEH), the CT and MRI findings of 14 histopathologically confirmed cases of HEH were retrospectively analyzed. Non-contrast and dynamic contrast-enhanced scans were conducted in all cases. A total of 229 lesions were detected in the 14 cases. All cases were classified as one of three types: (i) Solitary nodular type (1 case, 7%); (ii) multifocal nodular type (11 cases, 79%); or (iii) diffuse type (2 cases, 14%). The diameter of the lesions ranged from 5 to 105 mm. For the first two types (solitary and multifocal nodular types), the CT findings included low density lesions with clear margins on non-contrast scans, centripetal enhancement in arterial phase, and homogeneous enhancement in the portal venous and delay phases. The findings of non-contrast MRI scans for these two types included low signal intensity on T1-weighted images, heterogeneous high signal intensity on T2 weighted images, and heterogeneous high signal intensity on diffusion-weighted images. The lesions were predominantly located in submarginal areas. On contrast enhanced MRI, the findings for the first two types included peripheral ring-like enhancement with a central low signal intensity ('black target-like' sign) and a central enhanced core surrounded by a low signal intensity halo ('white target like' sign). The findings for the third HEH type (diffuse type) on CT and MRI scans included low density or heterogeneous signal intensity lesions involving regions of part or the whole liver, coalescent lesions ('strip-like' sign), and gradual enhancement along central vessels ('lollipop' sign). Collectively, these findings indicate that the 'white target-like' sign, 'black target-like' sign, 'lollipop' sign and 'strip-like' sign, in addition to capsular contraction and submarginal location, on CT and MRI imaging may have implications for the diagnosis of HEH. Furthermore, a variety of MRI sequences may provide additional information for the differential diagnosis of HEH. PMID- 26998065 TI - Bone morphogenetic protein 7 is associated with the nodal invasion of colon cancer. AB - Environmental and genetic factors interact in the process and treatment of colon cancer, although the underlying mechanisms remain elusive. The aim of the study was to examine the role of whether bone morphogenetic protein 7 (BMP7) is involved in the progression of colon cancer under local intratumoral infiltration lymphocytes. A total of 46 cases of pathologically confirmed specimens were obtained from patients with nodal invasion of colon cancer. The patients were subdivided into three groups based on the nodal invasion stages (N0, N1 and N2). Eleven cases without nodal invasion of colon cancer served as the control group (N0). The phenotype of CD45+, CD4+, CD8+, CD25+ and CD56+ cells and the expression of BMP7 were confirmed by immunofluorescence. The association between BMP7 expression and CD45+/CD4+CD25+/CD8+ cells infiltration was analyzed. The density of CD4+CD25+ T cells within the tumor was associated with nodal invasion in patients with colon cancer. More importantly, the expression of BMP7 was observed in the majority of the cancer tissues. The co-expression pattern of BMP7 in colon cancer cells and intratumor CD4+CD25+ T cells was associated with nodal invasion of colon cancer. In conclusion, the results have shown that the co expression of BMP7 is inversely associated with the infiltration of CD4+CD25+ T cells of colon cancer. The results suggest the combination of adaptive immunotherapy and biological drugs impact the treatment strategy for colon cancer in distinct clinical settings. PMID- 26998066 TI - Evaluation of the clinical characteristics, management, and prognosis of 103 patients with gastric mucosa-associated lymphoid tissue lymphoma. AB - The diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is difficult owing to its non-specific symptoms and various endoscopic findings. Treatments such as radiotherapy (RT) for localized and chemotherapy (CT) for advanced stages of the disease are employed. The aim of the present study was to examine the clinical characteristics and prognostic factors of Helicobacter pylori (H. pylori) eradication (HPE) in patients with gastric MALT lymphoma. The medical records of 103 patients with gastric MALT lymphoma for the period 2001 2013, were analyzed. The 103 median age of the patients was 53 years and the male to female ratio was 1:1. Serum lactate dehydrogenase and beta2-microglobulin were within normal range. Macroscopically, the most commonly involved site was the antrum, followed by the corpus and fundus. A total of 97 patients (94%) tested positive for H. pylori. Forty patients (39%) had stage I, 35 patients (35%) had local or distant nodal involvement, 20 of 103 patients had stage IIIE (19%) and 8 of 103 patients had stage IV (7%) disease. Complete remission, after HPE, was achieved in 54 of the 69 patients (78%) that were H. pylori-positive and in 2 of the 4 patients (50%) that were H. pylori-negative. HPE had a superior trend in the H. pylori-positive patients although no significant difference was identified in the two groups (p=0.194). In patients with advanced disease, the 5-year progression-free survival (PFS) and overall survival (OS) estimates were significantly improoved for patients receiving HPE with CT or RT than those receiving CT or RT (p=0.046 and 0.035, respectively). The multivariate analysis revealed that, the advanced stages were independently associated with shorter PFS, and the modified-International Prognostic Index (m-IPI) (>=2) was associated with shorter OS. In conclusion, gastric MALT lymphoma had a favorable outcome with a high OS rate. HPE was an effective treatment for gastric MALT lymphoma. The patients with advanced stages and m-IPI (>=2) had a much worse prognosis. PMID- 26998067 TI - A large schwannoma of the middle mediastinum: A case report and review of the literature. AB - Schwannoma of the mediastinum is a rare and typically benign type of tumor. The present study describes the case of a 61-year-old woman who presented with a continuous cough and facial edema. Pre-operative chest radiography, enhanced computed tomography (CT) and three-dimensional CT scans identified a well circumscribed mass. The large cyst, measuring 6.5*6.1*5.0 cm, was located anterior to the trachea and posterior to the superior vena cava. The mass was observed to be in close proximity to the right pulmonary hilum and the superior vena cava was flattened due to the pressure on the right vagus nerve. Therefore, the encapsulated tumor was completely resected under thoracoscopy and was subsequently diagnosed as a benign schwannoma upon pathological examination. The respiratory tract symptoms and facial edema resolved immediately after the surgery, and no recurrence was observed during the 6-month follow-up period. At the time of writing, the patient remained alive. The present study records the rarely successful resection of a middle mediastinal tumor by video-assisted thoracoscopy. PMID- 26998068 TI - Intercellular adhesion molecule 1 is a sensitive and diagnostically useful immunohistochemical marker of papillary thyroid cancer (PTC) and of PTC-like nuclear alterations in Hashimoto's thyroiditis. AB - Intercellular adhesion molecule 1 (ICAM-1) is important in the progression of inflammatory responses. Recently, increased levels of ICAM-1 have been reported in a number of types of malignancy. The present study aimed to investigate ICAM-1 expression in papillary thyroid cancer (PTC) and in Hashimoto's thyroiditis (HT) with PTC-like nuclear alterations, and to assess the predictive value of ICAM-1 in thyroid lesions. ICAM-1 expression was retrospectively investigated in 132 consecutive cases of PTC, 72 cases of HT, 10 of follicular cancer, 15 of follicular adenoma, 16 of nodular goiter and 8 samples of normal thyroid tissue using immunohistochemical analyses, and in 42 PTC patients using western blotting. ICAM-1 expression was not detected in normal follicular cells, follicular lesions (adenoma and cancer) and benign nodular hyperplasia, but was frequently overexpressed in PTC cells. ICAM-1 overexpression was associated with extra-thyroidal invasion and lymph node metastasis; no association was found with age, gender, tumor size, multifocality, pathological stage, recurrence or distant metastasis. ICAM-1 expression in HT patients with PTC-like nuclear alterations was significantly higher than that in HT cases with non-PTC-like features. Compared with antibodies against cytokeratin 19, galectin-3 and Hector Battifora mesothelial-1, ICAM-1 was the most sensitive marker for the detection of PTC-like features in HT. These findings demonstrate that ICAM-1 expression is upregulated in PTC and in HT with PTC-like nuclear alterations. This feature may be an important factor in the progression of cancer of the thyroid gland. PMID- 26998069 TI - Pseudolaric acid B activates autophagy in MCF-7 human breast cancer cells to prevent cell death. AB - Pseudolaric acid B (PAB) has been demonstrated to exert antitumor effects in MCF 7 human breast cancer cells. The present study aimed to investigate the mechanism of resistance to PAB-induced cell death. Following incubation with 4 uM of PAB for 3 days, the majority of MCF-7 cells became senescent, while some retained the same morphology as control cells, as assessed using a senescence detection kit. Additionally, 36 h of treatment with 4 uM of PAB increased the positive staining of autophagy markers, as shown by monodansylcadaverine and acridine orange staining. Western blot analysis indicated that this treatment also increased expression of the autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3. Furthermore, treatment with PAB and the autophagy inhibitor 3-methyl adenine significantly decreased the ratio of autophagy, as assessed by flow cytometric analysis of monodansylcadaverine staining density (P<0.001), and increased the ratio of cell death, as assessed by MTT analysis (P<0.001). This indicated that autophagy promotes cell survival as a resistance mechanism to PAB treatment. Additionally, the present study demonstrated that PAB treatment did not affect the mitochondrial membrane potential, which may be related to autophagy. Increased Bcl-2 expression may explain why PAB did not affect the mitochondrial membrane potential. A Bcl-2 binding test demonstrated that PAB treatment inhibits the binding of Bcl-2 and Beclin-1, which may free Beclin-1 to participate in autophagy. Therefore, the present study demonstrated that autophagy may be activated by PAB treatment in human breast cancer MCF-7 cells, contributing to resistance to cell death. PMID- 26998070 TI - Downregulation of HIF-1alpha inhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells. AB - Lung cancer, specifically non-small cell lung cancer (NSCLC), is the leading cause of cancer-associated mortality in the world. In previous years, almost no significant advancements have been made towards the molecular characterization of NSCLC, which highlights the requirement for novel target genes. Hypoxia inducible factor-1alpha (HIF-1alpha) is known to be essential in tumorigenesis, as it regulates the expression of numerous factors that are involved in angiogenesis, cellular proliferation and apoptosis. However, no direct association between HIF 1alpha and NSCLC treatment has previously been established. The aim of the present study was to characterize the effect of HIF-1alpha on NSCLC and to explore the possible mechanism. Additionally, HIF-1alpha small interfering (si)RNA and diamminedichloroplatinum (DDP) were used in combination to explore the combined effects on NSCLC cells. Lung carcinoma NCI-H157 cells were treated with HIF-1alpha small interfering (si)RNA, 5 ug/ml DDP or a combination of the two, and the proliferation, apoptosis and invasion ability of the cells were detected using a cell counting kit-8 assay, Annexin V/propidium iodide staining and a Transwell assay, respectively. In addition, the protein levels of caspase 3/9, anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)PI3K, protein kinase B (AKT), p-AKT, extracellular signal-regulated kinase (ERK) and p-ERK were detected using western blot analysis. Similar to DPP treatment, HIF-1alpha siRNA treatment may reduce cell proliferation and the invasiveness of tumor cells while promoting apoptosis. Additionally, HIF-1alpha siRNA may increase the levels of the apoptotic proteins caspases 3 and 9 and inhibit the expression of Bcl-2. These anti-tumor effects may be acting through the VEGF/PEDF, PI3K/AKT and Raf/mitogen-activated protein kinase kinase/ERK signaling pathways. The effects of HIF-1alpha siRNA may be strengthened by DDP. The present data indicated that HIF-1alpha siRNA is important in the inhibition of NSCLC cells. Additionally, the effects of HIF 1alpha siRNA may be strengthened by DDP, which suggests that HIF-1alpha siRNA may be combined with DDP for the treatment of tumors. PMID- 26998071 TI - miR-196b regulates gastric cancer cell proliferation and invasion via PI3K/AKT/mTOR signaling pathway. AB - miR-196b plays a significant role in the regulation of tumor pathogenesis and progression by promoting tumor cell proliferation, invasion and metastasis. In order to explore the effects of miR-196b on the proliferation and invasion ability of gastric cancer cells and the involved mechanisms, in the present study the lentivirus expression vector miR-196b was constructed and transfected into the human gastric cancer cell line MKN28. The cell proliferation and invasion ability were observed and the expression of PI3K/AKT/mTOR protein and mRNA were analyzed following upregulation of the expression of miR-196b. 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results revealed that the proliferation of MKN28 cells was notably increased following upregulation of the expression of miR-196b (P<0.01). Flow cytometry analysis demonstrated that miR-196b decreased the ratios of cells in the GO/G1 stage but increased the ratios in S and G2 stage (P<0.05). Furthermore, the cell clone formation and trans-membrane rates were increased following upregulation of the expression of miR-196b (P<0.01). The nude mouse tumor growth test revealed that tumor growth was more rapid following upregulation of the expression of miR-196b. The expression of PI3K/AKT/mTOR protein and mRNA were increased following upregulation of the expression of miR-196b. We concluded that upregulation of miR 196b promotes the proliferation and invasion ability of gastric cancer cells by regulating the PI3K/AKT/mTOR pathway. PMID- 26998072 TI - Association between ALDH1+/CD133+ stem-like cells and tumor angiogenesis in invasive ductal breast carcinoma. AB - The growth and metastasis of tumors is dependent on angiogenesis; however, the association between tumor stem cells (TSCs) and tumor angiogenesis remains to be elucidated. The present study aimed to investigate the expression of the TSC markers aldehyde dehydrogenase 1 (ALDH1) and cluster of differentiation 133 (CD133) in invasive ductal breast carcinoma, and identify their correlation with tumor angiogenesis. Stem-like cells from the breast tissue of 120 patients, who were diagnosed with invasive ductal breast carcinoma at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, Henan, China) between January 2009 and December 2010, were collected by surgical resection and analyzed using immunohistochemical double staining. The expression of the vascular markers CD34, CD105 and vascular endothelial growth factor (VEGF) were determined using single staining. Overall, 25.83% (31/120) of the specimens contained a large number of ALDH1+/CD133+ stem-like cells (ALDH1+/CD133+ tumor). ALDH1+/CD133+ expression is associated with microvessel density, VEGF-positive rate and estrogen receptor expression (P<0.05); however, ALDH1+/CD133+ expression was not associated with age, tumor diameter, lymph node metastasis, histological classification, progesterone receptor expression or human epidermal growth factor receptor 2 expression (P>0.05). The ALDH1+/CD133+ tumor phenotype and expression of VEGF were identified to be correlated in the present study (P=0.020). The present study revealed a close association between breast cancer TSC markers, including ALDH1 and CD133, and tumor angiogenesis. The results of the present study may provide a novel target and treatment strategy for future studies investigating tumor growth and metastasis. PMID- 26998073 TI - Remission of ALK-negative primary pulmonary inflammatory myofibroblastic tumor on treatment with clarithromycin: A case report and review of the literature. AB - Inflammatory myofibroblastic tumors (IMTs) belong to an intermediate group of soft-tissue tumors, they are relatively rare but exhibit a wide range of pathologies, from benign to malignant. At present, no standard treatment has been established, however, it is known to be important to determine the grade of malignancy of the tumor, prior to treatment. The present study reports a 73-year old female patient with no clinical manifestations, who, when examined radiographically at a health check exhibited bilateral thoracic infiltrative shadows and nodular shadows by chest CT. A metastatic tumor or an organizing pneumonia were suspected. Blood examination showed no abnormal findings, and a pathological diagnosis of IMT was given from the histological findings of the tissue extracted by video-assisted thoracic surgery. Histological analysis established the lack of expression of anaplastic lymphoma kinase (ALK1) and immunoglobulin subtype G4 (IgG4). Alteration of the radiological shadows was observed over several weeks, and after concluding that chronic inflammation was worsening the patient's condition, clarithromycin was administered as a long-term macrolide therapy. The IMT decreased in size, and eight months later it had almost resolved. The patient was last reported to be maintaining a stable condition with no relapse. Some IMT cases have malignant pathology, and should be carefully followed-up. However, in the present case, where the IMT is both ALK1 negative and IgG4-negative, its biological immune responsiveness appears to differ from positive cases, and an inflammatory response was predominant. Clarithromycin, has immunomodulatory and anti-inflammatory effects and appeared to be effective in treating the IMT of the patient in the present study. PMID- 26998074 TI - TOX3 protein expression is correlated with pathological characteristics in breast cancer. AB - TOX3 is a newly identified gene that has been observed to correlate with breast cancer by genome-wide association studies (GWAS) in recent years. In addition, it has been noted that single-nucleotide polymorphisms (SNPs) in the TOX3 gene have a strong correlation with estrogen receptor (ER)-positive tumors. However, the role of TOX3 in breast carcinoma development is still unclear. There are limited studies on the subject of TOX3 mRNA expression in breast tumors and little information on the variation of TOX3 protein expression in relation to the clinical pathological features in breast cancer and healthy tissues. In this study, we characterize the protein expression of TOX3 in breast tumors with respect to various clinical and pathological characteristics and explore the correlation between TOX3 protein expression and ER-positive tumors. A breast cancer tissue microarray containing 267 human breast tumors and 25 healthy controls, breast cancer cell lines (ZR-75-1, MDA-MB-231, MCF-7 and Bcap-37) with positive or negative ER expression, tumor tissues and matched controls were used to analyze the protein expression levels of TOX3 by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction. Among the 267 breast tumor specimens, ER expression was detected in 66 tumor tissues. The expression levels of TOX3 increased in breast carcinoma tissue compared with controls, and were higher in advanced carcinoma (T3 and T4), lymph node metastases tissues (N2) and stage III tissues. Furthermore, TOX3 protein expression was more intense in ER-positive tumors, but did not demonstrate a statistical significance. However, it was significantly increased in ER-positive breast cancer cell lines (ZR-75-1, MCF-7 and Bcap-37) compared with the MDA-MB-231 cell line, which had ER-negative expression. Our findings provide support to the hypothesis that TOX3 has a strong correlation with the development of breast cancer. The current study is likely to assist in investigating the mechanisms involved in breast cancer development. PMID- 26998076 TI - Therapy for thoracic lumbar and sacral vertebrae tumors using total spondylectomy and spine reconstruction through posterior or combined anterior-posterior approaches. AB - The present study aimed to analyze the indications, feasibility, safety and clinical effects of total spondylectomy and spine reconstruction through posterior or combined anterior-posterior approaches for thoracic lumbar and sacral vertebrae tumors. Between December 2009 and May 2012, 10 patients with thoracic lumbar and sacral vertebrae tumors were retrospectively analyzed. Different surgical indications and approaches were used according to the affected segments, the extent of lesion involvement and the specific pathology results. One-stage posterior or combined anterior-posterior total spondylectomy and reconstruction was used for the treatment of complicated thoracic lumbar and sacral vertebral malignant tumors and invasive benign tumors. The duration of surgery, levels of intraoperative blood loss and transfusions, and the clinical effects were observed. The average surgical duration was 6.8 h (range, 4.8-12 h), with an average blood loss level of 3,200 ml (range, 1,500-10,000 ml) and an average transfusion level of 2,500 ml. During the average 15 months (range, 3-29 months) follow up, two patients succumbed and one patient experienced tumor recurrence. Neither tumor reoccurrence nor metastasis was observed in all other patients. Personalized surgical indications and approaches according to the affected segments, the extent of lesion involvement and the specific pathology results would aid in the reduction of pain, the improvement of nerve function and the reduction of tumor recurrence. PMID- 26998075 TI - Association between histopathological subtype, 18F-fluorodeoxyglucose uptake and epidermal growth factor receptor mutations in lung adenocarcinoma. AB - The aim of the present study was to investigate the association between histopathological subtypes, epidermal growth factor receptor (EGFR) mutations and 18F-fluorodeoxyglucose (FDG) uptake in patients with lung adenocarcinoma (ADC). The cases of 97 patients with lung ADC who underwent 18F-FDG positron emission tomography-computed tomography prior to surgical resection were retrospectively reviewed. The patients were stratified according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification, and graded using a histopathological scoring system. EGFR mutations were identified. Clinicopathological characteristics associated with EGFR mutation status were evaluated using univariate and multivariate analyses. EGFR mutation was identified in 45.4% of the patients and was associated with gender, smoking history, maximum standardized uptake value (SUVmax) and histopathological score. ADC patients with a low SUVmax were more likely to exhibit EGFR mutations compared with patients with a high SUVmax (P=0.018). Patients with a lower histopathological score possessed a significantly lower SUVmax compared with patients with a higher score (P<0.001). Furthermore, the histopathological score and smoking history of the patients were identified to be independent predictors for EGFR mutations, according to multivariate logistic regression analysis. In conclusion, SUVmax and EGFR mutations were associated with lung ADC patients stratified according to the IASLC/ATS/ERS classification. Overall, SUVmax has the potential to be a useful marker in stratifying pre-operative patients with lung ADC and identifying EGFR mutations. PMID- 26998077 TI - Laricitrin suppresses increased benzo(a)pyrene-induced lung tumor-associated monocyte-derived dendritic cell cancer progression. AB - Benzo(a)pyrene (BaP) stimulates lung cancer cells, promoting monocyte-derived dendritic cells to secrete soluble factors, including heparin binding-epidermal growth factor and C-X-C motif chemokine 5. The secretions from monocyte-derived dendritic cells stimulate the progression of lung cancer cells, including the migration and invasion of cells. To the best of our knowledge, these secretions remain unknown, and require additional study. The present study identified that treatment with BaP-H1395-tumor-associated dendritic cell-conditioned medium had the most marked effect on cell migration and invasion. This result may be associated with the female gender, stage 2 adenocarcinoma or mutation of the proto-oncogene B-Raf (BRAF), according to the cell line background. Laricitrin, a dietary flavonoid derivative present in grapes and red wine, suppresses certain factors and decreases the progression of lung cancer cells that are promoted by BaP in the lung cancer tumor microenvironment. The results of the present study suggest that prolonged exposure to BaP exacerbates lung cancer, particularly in female lung cancer patients with the BRAF mutation, but that laricitrin may ameliorate this effect. PMID- 26998078 TI - Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence. AB - The present study aimed to investigate the expression level of HOX transcript antisense RNA (HOTAIR) in hepatocellular carcinoma (HCC) and its association with various clinicopathological characteristics, and to further explore the molecular mechanisms of HOTAIR function in HCC. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in 60 paired fresh HCC samples and adjacent normal liver tissue samples. The association between HOTAIR expression and clinicopathological parameters was analyzed. Lentivirus-mediated HOTAIR-specific small hairpin RNA vectors were transfected into HepG2 cells. Cell proliferation and invasion in vitro were examined by MTT and Transwell assays, respectively. A xenograft model was used to analyze the tumorigenesis of liver cancer cells in vivo. In addition, semi quantitative RT-PCR was used to detect the expression level of Wnt/beta-catenin signaling molecules under the condition of HOTAIR inhibition. The results revealed that the expression level of HOTAIR in HCC tissues was higher than that in adjacent non-cancerous tissues. HOTAIR expression was significantly associated with poor tumor differentiation (P=0.002), metastasis (P=0.002) and early recurrence (P=0.001). In vitro, the inhibition of HOTAIR in liver cancer cells resulted in the suppression of cell proliferation and invasion. HOTAIR depletion significantly inhibited the rate of growth of liver cancer cells in vivo. Furthermore, the expression levels of Wnt and beta-catenin were downregulated when HOTAIR expression was suppressed. In conclusion, HOTAIR is important in the progression and recurrence of HCC, partly through the regulation of the Wnt/beta catenin signaling pathway. Targeting HOTAIR may be a novel therapeutic strategy for HCC. PMID- 26998079 TI - Percutaneous kyphoplasty for the treatment of spinal metastases. AB - The bones are the most common location for metastases, which may cause severe pain and damage, including osteolytic destruction and fractures. Pathological fractures of the spine are extremely painful and cause significant disability and morbidity in patients. Traditional open surgery has numerous complications, and radiation therapy may take weeks to become effective. To avoid the trauma and complication of open surgery, percutaneous kyphoplasty (PKP) is a minimally invasive procedure that has played a great role in the treatment of spinal metastases over the past several years. To evaluate the efficacy and safety of the treatment of spinal metastasis using PKP, the present study evaluated 282 patients who had received PKP between April 2009 and June 2014. The efficacy of PKP was evaluated using the visual analog scale for pain (VAS), Karnofsky performance score (KPS) and quality of life (QOL) score (short form with 36 questions). The KPS and QOL were measured pre-operatively and 3 months post operatively. In addition, radiographical data, including the degree of restoration of the kyphotic angle and the anterior vertebral height, and leakage of bone cement, were measured. The safety of the surgery was assessed by complications and side effects reported during or subsequent to surgery. The present study measured the parameters prior to the surgery and at 24 h, 3 months, 6 months and 1 year post-surgery, as well as at the last follow-up date. The range of the follow-up time was between 105 days and 15 months (mean, 401 days). The 282 patients underwent successful operations and the pain felt by the patients prior to the surgery was significantly alleviated. In addition, the analgesic intake of patients greatly decreased following PKP. KPS improved prior to and 3 months after the surgery. QOL also improved prior to and 3 months after the surgery. Radiographical data demonstrated that the kyphotic angle decreased following PKP, and the anterior vertebral height increased. Paravertebral leakage of bone cement occurred in 10 patients through a cortical defect, but without spinal cord compression or pulmonary embolism. Therefore, as a minimally invasive procedure, PKP may not only rapidly relieve the pain and disability experienced by patients, but it may also restore the kyphotic angle observed at the 1-year follow-up. Notably, PKP may safely improve the QOL of patients. PMID- 26998080 TI - Primary pulmonary leiomyosarcoma: A case report. AB - Primary pulmonary leiomyosarcoma (PPL) is an extremely rare malignant tumor. It has been revealed that PPL may originate from the smooth muscle of the pulmonary parenchyma, pulmonary arteries and bronchi. Patients with PPL may be asymptomatic or present with symptoms similar to those observed in other primary lung tumors. The present study reports the case of a 48-year-old man who presented with a lung mass and underwent a right upper-middle lobe bronchoscope tumor resection. The patient was subsequently diagnosed with PPL. Following the bronchoscopic tumor resection, chemotherapy was administered to the patient; however, the patient succumbed to the disease after the second cycle of chemotherapy. PMID- 26998081 TI - Primary adenocarcinoma of the renal pelvis, ureter and the urinary bladder: A case report and review of the literature. AB - Primary adenocarcinoma is a rare type of urological neoplasm. The present study reports the case of a 55-year-old man with multifocal adenocarcinoma of the renal pelvis, ureter and urinary bladder that occurred in association with a large cystic calculus and perinephric abscess. The patient had suffered from gross hematuria for 2 years and right flank pain for 2 months. Following a series of investigations, a large cystic calculus with multiple tumors in the renal pelvis and ureter was identified. Multifocal tumors and a large calculus were located in the bladder using a cystoscope. The pathological report of 3 individual biopsies revealed a moderately differentiated tubular adenocarcinoma. Right nephrectomy, ureterectomy, radical cystectomy and left ureterocutaneostomy were performed. The pathological investigation revealed a moderately differentiated adenocarcinoma of the renal pelvis, ureter and urinary bladder. No additional treatment was administered and the patient remains alive at follow-up without disease recurrence or metastasis. Although uncommon, the development of a tumor is possible in patients that possess long-standing urolithiasis, particularly when accompanied by hydronephrosis or infection. PMID- 26998082 TI - Continuous negative pressure-flush through a dual tube for the treatment of a complicated pharyngeal fistula: A case report. AB - The treatment of pharyngeal fistulas is complicated. It is more difficult to deal with pharyngeal fistula following surgical treatment for hypopharynx carcinoma, particularly in cases of pectoralis major muscle flap repair. The present study describes the case of a 56-year-old man who presented with a highly differentiated pharyngeal squamous cell carcinoma located at the right side of the hypopharynx. The patient underwent a total laryngectomy and a right functional carotid dissection and tracheostomy; this was followed by post operative radiotherapy. A pharyngeal fistula subsequently developed, but an attempt to repair this with a pectoralis major muscle flap failed. The complicated pharyngeal fistula was treated via continuous negative pressure-flush through a dual tube, without the requirement for incision, daily dressing or antibiotics. The favorable patient outcome represented a positive result, which was also able to reduce the psychological burden of the patient and improve their quality of life. PMID- 26998083 TI - Synovial osteochondromatosis of the wrist joint: A case report. AB - Synovial osteochondromatosis is a rare condition in which multiple cartilaginous nodules proliferate within the synovial membranes of joints, tendon sheaths or bursae. In general, a complete synovectomy is an effective method to treat this disease. Commonly involved joints are the knee, glenohumeral joint, elbow, hip and ankle, although any articulation may be affected. However, synovial osteochondromatosis occurs rarely in the wrist, and there have been a lack of reports of this occurrence in the literature. The current study presents a case of synovial osteochondromatosis in a 33-year-old man, who was admitted in 2014 with the symptom of swelling of the left wrist joint for 2 years. The swelling had become increasingly painful over the previous 2 months. Physical examination revealed local tenderness and a soft pliable mass, with no involvement of the skin and with moderate pain. X-ray, computed tomography and magnetic resonance imaging of the left wrist revealed a lump at the volar radial side of the left wrist joint without any bone erosion. The lesion was subsequently excised. Histological examination resulted in a diagnosis of osteochondromatosis, which was not considered prior to the surgery. The present case was reported with the aim of analyzing the clinical, imaging characteristic and therapeutic modalities of synovial osteochondromatosis of the wrist. While there was no evidence of recurrence for the subsequent 4 months of post-operative follow-up in the present case, the long-term efficacy of surgical excision requires extended observation. PMID- 26998085 TI - Expression of the galectin-9-Tim-3 pathway in glioma tissues is associated with the clinical manifestations of glioma. AB - Glioma is known to induce local and systemic immunosuppression, which inhibits antitumor T cell responses. The galectin-9-Tim-3-pathway negatively regulates T cell pathways in the tumor immunosuppressive environment. The present study assessed the expression of Tim-3 and galectin-9 in glioma patients, and evaluated the association between the expression of Tim-3 and galectin-9 with clinical characteristics. The present study identified that Tim-3 expression was significantly increased in peripheral blood T cells of glioma patients compared with those of healthy controls, and was additionally increased on tumor infiltrating T cells. The expression of Tim-3 on tumor-infiltrating T cells was associated with the World Health Organization (WHO) grade of glioma, but negatively correlated with the Karnofsky Performance Status score of the glioma patients. Immunohistochemical analysis revealed that the expression of galectin-9 in tumor tissues was associated with Tim-3 expression on tumor-infiltrating T cells and the WHO grade of glioma. These findings suggest that the galectin-9-Tim 3 pathway may be critical in the immunoevasion of glioma and may be a potent target for immunotherapy in glioma patients. PMID- 26998084 TI - Overexpression of DEK is an indicator of poor prognosis in patients with gastric adenocarcinoma. AB - Increased expression of the human DEK proto-oncogene (DEK) gene has been associated with numerous human malignancies. The DEK protein is associated with chromatin reconstruction and gene transcription, and is important in cell apoptosis. The present study aimed to elucidate the role of DEK with regard to gastric adenocarcinoma tumor progression and patient prognosis. DEK protein expression was analyzed using immunohistochemistry in 192 tumors paired with adjacent non-cancerous gastric mucosa that had been surgically resected from patients with primary gastric adenocarcinoma. The association between DEK expression and the clinicopathological characteristics of the patients was evaluated using the chi2 test and Fisher's exact test. The survival rates of the patients were calculated using the Kaplan-Meier method. Cox analysis evaluated the association between the expression of DEK and the survival rate of the patients. The DEK protein was expressed in 84 patients with gastric adenocarcinoma (43.8%) and in 20 of the paired normal gastric mucosa tissues (11.5%). The DEK expression rate was found to be associated with tumor size (P=0.006), tumor grade (P=0.023), lymph node metastasis (P=0.018), serous invasion (P=0.026), tumor stage (P=0.001) and Ki-67 expression (P=0.003). Furthermore, patients with gastric adenocarcinoma that expressed DEK had decreased disease-free (log-rank, 16.785; P<0.0001) and overall (log-rank, 15.759; P<0.0001) survival rates compared with patients without DEK expression. Patients with late-stage gastric adenocarcinoma that expressed DEK exhibited a lower overall survival rate compared with patients without DEK expression (P=0.002). Additional analysis revealed that DEK expression was an independent prognostic factor for the prognosis of gastric adenocarcinoma (hazard ratio, 0.556; 95% confidence interval, 0.337-0.918; P=0.022). From the results of the present study, it can be concluded that the detection of DEK protein expression in gastric adenocarcinoma tissues may be important for the diagnosis and prognosis of patients, and may be a targeted therapy for the treatment of gastric adenocarcinoma. PMID- 26998086 TI - Expression of tumor necrosis factor-alpha-induced protein 8 in stage III gastric cancer and the correlation with DcR3 and ERK1/2. AB - Tumor necrosis factor (TNF)-alpha-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r=0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC. PMID- 26998087 TI - B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer. AB - B7-H3 and B7-H4 belong to the peripheral membrane protein B7 family and are hypothesized to regulate immunity. These proteins are expressed in human pancreatic cancer (PC), but their prognostic significance is poorly understood. The present study examined the association between B7-H3 and B7-H4 expression and the overall survival time in patients with PC that underwent surgery at the Second Affiliated Hospital to Zhengzhou University between April 2000 and January 2009. Immunohistochemical analysis demonstrated that B7-H3 and B7-H4 were expressed in 35 (88%) and 30 (75%) tumor tissue samples, respectively, which were obtained from 40 patients with PC. Statistical analysis revealed that B7-H3 expression was associated with an early tumor-node-metastasis stage (stage I and II; P<0.01), and B7-H4 expression was associated with tumors located in the body and tail of the pancreas (P<0.01) and lymph node metastasis (P=0.02). In addition, using Spearman's rank correlation coefficient, the present study demonstrated a positive correlation between B7-H3 expression and B7-H4 expression (r=0.37; P=0.02) in tumor samples. B7-H4 expression (P=0.01), tumors located in the pancreatic body and tail (P<0.01), lymph node metastasis (P=0.02) and combined B7-H3 and B7-H4 expression (P<0.01) were indicators of a poor overall survival time. However, solitary B7-H4 expression (P=0.03) and combined B7-H3 and B7-H4 expression (P=0.04) remained significant prognostic factors following adjustment for other prognostic factors in a multivariate Cox's proportional hazards regression model. Therefore, the present results indicate that solitary B7-H4 expression and a combination of B7-H3 and B7-H4 expression are independent predictors of a poor prognosis in patients with PC. PMID- 26998088 TI - NRAGE promotes the malignant phenotype of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a fatal disease, primarily due to the limited effective therapies available for patients with advanced or recurrent stages of the disease. Therefore, in order to improve patient prognosis, it is important to identify an informative biomarker for HCC progression, as well as a molecular target for therapy. Neurotrophin receptor-interacting melanoma antigen-encoding protein (NRAGE), a member of the type II melanoma-associated antigen family, mediates apoptosis and cell death through interactions with a wide range of proteins, and is implicated as a tumor suppressor or oncoprotein depending on cell type. However, the role of NRAGE in HCC is currently unknown, therefore, the present study aimed to identify the underlying function of NRAGE in HCC tumorigenesis. Resected tumor and non-cancerous liver tissues from 151 patients with HCC, alongside HCC cell lines, were analyzed by polymerase chain reaction and immunohistochemical techniques to determine NRAGE expression levels, as well as the expression levels of potential genes encoding interacting proteins. It was demonstrated that the expression levels of NRAGE mRNA correlated significantly with those of apoptosis-antagonizing transcription factor (AATF), and were not affected by cirrhosis in non-cancerous liver tissues when compared to elevated levels in HCC tissues. The expression patterns of NRAGE protein and mRNA were consistent among 30 representative specimen pairs. Furthermore, increased NRAGE expression in patients with HCC correlated significantly with a shorter disease specific survival time, and was identified as an independent prognostic factor via multivariate analysis (hazard ratio, 2.23; 95% confidence interval, 1.06 3.83; P=0.020). Therefore, the results of the present study indicated that increased NRAGE expression affects HCC progression via its interaction with AATF, and may represent a novel biomarker and molecular target for the treatment of HCC. PMID- 26998089 TI - Totally laparoscopic D2 radical distal gastrectomy using Billroth II anastomosis: A case report. AB - Here, we present our first case of totally laparoscopic D2 radical distal gastrectomy using Billroth II anastomosis and evaluate its effectiveness in terms of minimal invasiveness, technical feasibility and safety for the resection of early gastric cancer. In the present case, only laparoscopic linear staplers were used for intracorporeal anastomosis. The time taken was 180 min, the anastomotic time was 15 min, the number of staples used was five, and the estimated blood loss was 30 ml. The first flatus was observed at 3 days, and a liquid diet was started at 6 days. The postoperative hospital stay was 8 days. No postoperative complications were noted with our case. In conclusion, totally laparoscopic Billroth II anastomosis using laparoscopic linear staplers for early gastric cancer is considered to be safe and feasible. PMID- 26998090 TI - Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study. AB - The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease. PMID- 26998091 TI - Combination of lactate calcium salt with 5-indanesulfonamide and alpha-cyano-4 hydroxycinnamic acid to enhance the antitumor effect on HCT116 cells via intracellular acidification. AB - Maintenance of a neutral intracellular pH (pHi) is favorable for the survival of tumors, and maintenance of highly acidic extracellular pH (pHe) facilitates tumor invasiveness. The aim of the present study was to investigate the antitumor effects of lactate calcium salt (CaLa), 5-indanesulfonamide (IS) and alpha-cyano 4-hydroxycinnamic acid (CA) via pH regulation in colon cancer cells. HCT116 cells were treated with CaLa, IS, CA and combinations of the three. Subsequently, the concentration of intracellular lactate was determined. pHi and pHe were measured using cell lysates and culture media. Colony formation assay, cell viability assay and western blot analysis were additionally performed to analyze the consequences of the pH changes. CaLa, IS, CA and combination treatments induced an increase in the concentration of intracellular lactate. Lactate influx into the tumor microenvironment produced an acidic pHi in colon cancer cells. Consequently, colony formation and cell viability were significantly decreased, as well as poly(adenosine diphosphate-ribose) polymerase degradation. The tumor microenvironment may be exploited therapeutically by disrupting the mechanism that regulates pHi, leading to cell apoptosis. The present study indicated that treatment with CaLa, IS and CA induced intracellular acidification via lactate influx, causing apoptosis of colon cancer cells. Additionally, the findings suggested that the combination of CaLa with IS and CA may enhance antitumor activity, and may provide a potential therapeutic approach for the treatment of colon cancer. PMID- 26998092 TI - Analysis of the expression of SDF-1 splicing variants in human colorectal cancer and normal mucosa tissues. AB - C-X-C motif chemokine ligand 12 (CXCL12), also termed stromal cell-derived factor 1 (SDF-1) is a small protein 8-14 kDa in length that is expressed as six isoforms, consisting of SDF-1alpha, SDF-1beta, SDF-1gamma, SDF-1delta, SDF 1epsilon and SDF-1theta. All six isoforms are encoded by the single CXCL12 gene on chromosome 10. This gene regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. The potential role of the novel CXCL12 splice variants as components of the CXCR4 axis in cancer development is not fully understood. The present study aimed to analyze the expression profile of the various SDF-1 isoforms and SDF-1 polymorphisms, and the association with the clinicopathological features and overall survival of patients with colorectal cancer (CRC). SDF-1 polymorphism analysis was performed using restriction fragment length polymorphism (RFLP) analysis in 73 histologically confirmed human CRC tissue samples at various stages of disease. The expression pattern of the SDF-1 isoforms was analyzed by reverse transcription-polymerase chain reaction in 40 histologically confirmed human CRC tissue samples obtained at various stages of disease, as well as in matched adjacent normal mucosa samples. The presence of the CXCL12 gene polymorphism rs1801157 demonstrated an association with local progression of the primary tumor, as indicated by the T stage. The frequency of the GG genotype was slightly increased in patients with stage 3 and 4 tumors (78.0%) compared with the incidence of the GA/AA genotype (69.5%; P=0.067). The expression of SDF-1beta was associated with the presence of metastases (P=0.0656) and the expression of SDF 1gamma was significantly associated with tumor size (P=0.0423). The present study is the first to analyze the association between the expression profile of the chemokine CXCL12 splice variants in human CRC tissues and their clinical relevance. The present results reveal that the CXCL12 G801A polymorphism is a low penetrance risk factor for the development of CRC, and was associated with the T stage. All six isoforms of SDF-1 were expressed in CRC tissues. The expression of SDF-1beta was found to be associated with metastases and SDF-1gamma appears to be a possible tumor marker for local tumor progression. PMID- 26998093 TI - Reduced expression of caspase-8 and cleaved caspase-3 in pancreatic ductal adenocarcinoma cells. AB - Pancreatic ductal adenocarcinoma (PDAC) is a rare neoplasm that affects the gastrointestinal system, and is characterized by a high mortality rate. It has been demonstrated that apoptosis has a significant role in the regulation of cancer cells. Therefore, the aim of the present study was to immunohistochemically assess the expression of proteins belonging to the caspase family, namely caspase-8, pro-caspase-3 and cleaved (active) caspase-3 in pancreatic cancer. The study group consisted of 29 patients exhibiting PDAC. Protein expression was evaluated by immunohistochemical methods. The expression of caspase-8 in normal cells was negative in 17.2% of cases and positive in 82.8% of cases. All cases demonstrated pro-caspase-3 expression in normal pancreatic cells, compared with 93.1% of cancer cells. Staining for activated caspase-3 was positive in 27 normal tissue cases, compared with positivity in only 10 cancer cases. Caspase-8 expression positively correlated with cleaved caspase-3 expression in the cytoplasm of cancer cells (P<0.002). Caspase-3 expression was identified to correlate with inflammatory peritumoral infiltration (P<0.015). No correlation was observed between caspase expression and any other clinicopathological parameters. The results of the present study demonstrated aberrant initiation of cancer cell apoptosis in PDAC via a decrease in caspase-8 expression, which may lead to disorders in the activation of effector caspase-3. PMID- 26998094 TI - Cytokine-induced killer cell therapy for the treatment of primary hepatocellular carcinoma subsequent to liver transplantation: A case report. AB - Liver cancer, of which the most common form is hepatocellular carcinoma (HCC), is one of the most lethal cancers worldwide. Immunotherapy based on the direct attack of tumor cells and the stimulation of an antitumor immune response may represent a novel strategy to control HCC recurrence and metastasis. The present study reports the case of a patient with HCC, and describes the safety and feasibility of successful administration with a mass of autologous activated T cells on numerous occasions subsequent to liver transplantation (LT), in order to kill the residual tumor cells and stimulate the immune system. A large number of infused activated T cells may pose a potential risk to the allograft. However, no acute or delayed adverse effects of cytokine-induced killer cell (CIK) therapy, or other symptoms of secondary acute host-versus-graft disease (HVGD), were observed. These observations demonstrate the relatively low toxicity of CIK infusion to a patient that has undergone LT, and more importantly, they demonstrate the feasibility of this immunotherapy for the patient, following successful LT. PMID- 26998095 TI - AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway. AB - The present study aimed to investigate the mechanism by which Aurora kinase A (AURKA) promotes cell migration and invasion in head and neck squamous cell carcinoma (HNSCC). Transwell assays were performed to investigate the cell migration and invasion abilities of AURKA, whilst western blotting was used to analyze the protein expression in FaDu and Hep2 cells, each treated with pharmacological inhibitors. Following the inhibition of AURKA, Akt and focal adhesion kinase (FAK), the migration and invasion of the FaDu and Hep2 cells decreased. The expression of phosphorylated (p)-AURKA and p-FAK (Y397) was observed to decrease following FaDu and Hep2 cell treatment with VX-680, a small molecular inhibitor of AURKA. The expression of p-Akt and p-FAK (Y397) ceased following treatment with the Akt inhibitor triciribine. The expression of p-FAK (Y397) decreased, however, p-Akt expression did not change following treatment with the FAK inhibitor TAE226. In conclusion, AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. PMID- 26998097 TI - Primary adenocarcinoma of the small intestine presenting as superior mesenteric artery syndrome: A case report. AB - Superior mesenteric artery syndrome (SMAS) is an uncommon cause of vomiting and weight loss due to compression of the third part of the duodenum by the superior mesenteric artery. Small bowel adenocarcinoma is an uncommon tumor, which is frequently delayed in diagnosis as its symptoms and signs are non-specific. The present study describes a case of SMAS occurring in a 51-year-old man, caused by intestinal obstruction secondary to a primary adenocarcinoma of the duodenal jejunal junction. To the best of our knowledge, the present case is the first report of small bowel adenocarcinoma masquerading as SMAS. The present case highlights the importance of considering the possibility of SMAS in patients with upper bowel obstruction caused by intestinal carcinoma. PMID- 26998098 TI - Pancreatic metastasis resulting from thymic neuroendocrine carcinoma: A case report. AB - Thymic neuroendocrine carcinoma (NEC) is a rare type of cancer. Unlike other thymic epithelial tumors and carcinoids originating in other locations, thymic NEC possesses a more aggressive biological behavior, including invasion to proximal structures, local recurrence and distant hematogenous metastasis. Distant metastasis is often observed in the bones, lungs, spleen, liver and adrenal glands. However, pancreatic metastasis resulting from thymic NEC is extremely uncommon, and only a few cases of patients with this disease have been reported. The current study presents the case of a patient with pancreatic metastasis resulting from thymic NEC. The patient was admitted to hospital with an anterior mediastinal neoplasm, which was identified using chest enhanced computed tomography. The patient underwent a monobloc excision of the tumor with resection of involved structures. Subsequently, a pathological diagnosis of atypical thymic carcinoid was provided, according to the morphological characteristics observed and the expression of neuroendocrine markers, as identified by immunohistochemistry. Following surgery, the patient received adjuvant chemotherapy and radiotherapy. However, ~2 years after surgery, metastasis at the pancreatic head was identified. The patient underwent a total pancreatectomy and splenectomy, and did not receive any post-operative therapies; however, the patient succumbed to the disease 9 months following surgery. Overall, the results from the present study demonstrate the clinical features of thymic NEC, which may aid with the diagnosis of this rare disease in other patients. PMID- 26998096 TI - Estradiol, TGF-beta1 and hypoxia promote breast cancer stemness and EMT-mediated breast cancer migration. AB - Breast cancer is one of the most common cancer types among women, acting as a distinct cause of mortality, and has a high incidence of recurrence. External stimuli, including 17beta-estradiol (E2), transforming growth factor (TGF)-beta1 and hypoxia, may be important in breast cancer growth and metastasis. However, the effects of these stimuli on breast cancer stem cell (CSC) regulation have not been fully investigated. In the present study, the proportion of cluster of differentiation (CD)44+/CD24-/low cells increased following treatment with E2, TGF-beta1 and hypoxia in MCF-7 cells. The expression of CSC markers, including SOX2, KLF4 and ABCG2, was upregulated continually by E2, TGF-beta1 and hypoxia. In addition, the expression levels of epithelial-mesenchymal transition associated factors increased following treatment with E2, TGF-beta1 and hypoxia. Therefore, the migration ability of E2-, TGF-beta1- and hypoxia-treated MCF-7 cells was enhanced compared with control cells. In addition, the enhancement of apoptosis by 5-flurouracil or radiation was abolished following treatment with E2, TGF-beta1 and hypoxia. These results indicate that E2, TGF-beta1 and hypoxia are important for regulating breast CSCs, and that the modulation of the microenvironment in tumors may improve the efficiency of breast cancer therapy. PMID- 26998099 TI - CXCL10 and CCL2 mRNA expression in monocytes is inversely correlated with the HLA DR lower fraction of monocytes in patients with renal cell carcinoma. AB - Circulating cluster of differentiation (CD)14+ human leukocyte antigen (HLA) DRlow/- monocytes, those with a lower HLA-DR expression or are negative for HLA DR, are considered to be involved in systemic immunosuppression in patients with several malignant tumors. However, few studies have investigated in detail the gene expression profile of CD14+HLA-DRlow/- monocytes. In the present study, the mRNA expression levels of immune-associated molecules in CD14+ monocytes isolated from healthy donors and patients with renal cell carcinoma (RCC) were analyzed. Consistent with previous studies, the percentage of HLA-DRlow/- cells in CD14+ monocytes was significantly increased in patients with RCC compared with healthy donors. In 3 of the 4 patients who underwent surgical resection of the primary tumor, the percentage of CD14+HLA-DRlow/- cells was significantly decreased following surgery. The mRNA expression levels of cyclooxygenase 2, transforming growth factor beta, interleukin 6R, chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-X-C motif) ligand 10 (CXCL10), oncostatin M, and vascular endothelial growth factor-A in CD14+ monocytes were quantified using reverse transcription-quantitative polymerase chain reaction. The results of the present study revealed that increased expression levels of CCL2 and CXCL10 were inversely correlated with the percentage of CD14+HLA-DRlow/- monocytes. This suggested that monocytes in RCC patients were immunologically suppressed, and that immunosuppression in RCC patients may be due, in part, to the dysfunction of circulating monocytes. PMID- 26998101 TI - Cutaneous and systemic plasmacytosis on the face: Effective treatment of a case using thalidomide. AB - Cutaneous and systemic plasmacytosis is an exceedingly rare condition that is identified in Japanese individuals in particular. The present study describes the case of a patient of mainland Chinese origin who manifested with red-brown macules, papules and plaques limited to the face. Identifying a therapy for cutaneous and systemic plasmacytosis is quite difficult, however, the present patient showed a good response to low-dose thalidomide. The exact mechanism of action is not yet clear, however, we hypothesize that thalidomide may function through decreasing the secretion of interleukin-6 and affecting the growth of plasma cells. PMID- 26998100 TI - High expression of LMO2 predicts a favorable outcome in adult patients with BCR/ABL negative B-cell acute lymphoblastic leukemia. AB - The LIM domain only protein 2 (LMO2) is a key regulator of hematopoietic stem cell development. Expression of LMO2 has been evaluated in B-cell lymphoma, T cell acute lymphoblastic leukemia and acute myeloid leukemia; however, information concerning its role in breakpoint cluster region/Abelson murine leukemia viral oncogene homolog 1 (BCR/ABL) negative B-cell acute lymphoblastic leukemia (B-ALL) remains limited. The present study investigated LMO2 expression using quantitative polymerase chain reaction in 85 adult patients with BCR/ABL negative B-ALL, and associated the expression of LMO2 with established prognostic factors. LMO2 expression levels in patients with BCR/ABL negative B-ALL was not significantly different compared with control individuals (P=0.25). However, LMO2 expression levels were associated with the immunophenotypical features of the patients; a high LMO2 expression was associated with a higher incidence of complete remission (P=0.03) and lower rate of relapse (P=0.01), and patients with a high LMO2 expression had a significantly improved overall survival rate (P=0.01) and disease-free survival (P=0.01). The present results suggest that LMO2 expression is a favorable prognostic marker in adult patients with BCR/ABL negative B-ALL and may be used as a diagnostic marker and therapeutic target. However, additional studies regarding its prognostic role in patients with BCR/ABL negative B-ALL are required. PMID- 26998102 TI - MicroRNA-524-5p suppresses the growth and invasive abilities of gastric cancer cells. AB - Previous studies have demonstrated that microRNAs (miRNAs) are associated with tumor development and progression. miRNA-524-5p (miR-524-5p) has been reported to be involved in the development and progression of several types of cancer, but its role in gastric cancer has not been fully elucidated to date. Therefore, the aim of the present study was to investigate the expression levels and function of miR-524-5p in human gastric cancer. The expression levels of miR-524-5p were assessed in gastric cancer specimens and cell lines, including MKN-45, SGC-7901 and MGC-803 cell lines and gastric epithelial mucosa GES-1 cells, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation and cell apoptosis assays and invasion analysis in gastric cancer cell lines were performed to evaluate the effects of miR-524-5p on gastric cancer cells in vitro. The expression levels of matrix metallopeptidase (MMP)-2 and MMP 9 were determined by RT-qPCR and western blot analysis. The expression of miR-524 5p was significantly decreased in gastric cancer tissues and cell lines. Additionally, the results of the in vitro experiments demonstrated that overexpression of miR-524-5p inhibited cell proliferation and invasion, and promoted cell apoptosis in gastric cancer cells. Human gastric cancer SGC-7901 and MGC-803 cell lines transfected with miR-524-5p exhibited reduced expression levels of MMP-2 and MMP-9. Taken together, the results of the present study indicated that miR-524-5p may function as a novel tumor suppressor gene in gastric cancer, and may serve as a biomarker and therapeutic target for the treatment of gastric cancer. PMID- 26998103 TI - Successful treatment of Lambert-Eaton myasthenic syndrome in a small cell lung cancer patient using 3,4-diaminopyridine: A case report. AB - Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction that is characterized by muscle weakness. LEMS is usually associated with cancer, most commonly small cell lung cancer (SCLC). The potassium-channel blocker 3,4-diaminopyridine (3,4-DAP), has been previously used for the symptomatic treatment of LEMS. 3,4-DAP increases the release of acetylcholine and prolongs the duration of nerve action potentials at the presynaptic membrane of the neuromuscular junction. The present study describes the case of a patient with LEMS and SCLC, for which the symptoms did not improve with anticancer therapy, but did so markedly following treatment with 3,4-DAP. The present study illustrates that 3,4-DAP is a useful treatment choice in patients with LEMS, particularly for patients who do not fully improve following anticancer therapy. PMID- 26998104 TI - S100A8/A9 is associated with estrogen receptor loss in breast cancer. AB - S100A8 and S100A9 are calcium-binding proteins that are secreted primarily by granulocytes and monocytes, and are upregulated during the inflammatory response. S100A8 and S100A9 have been identified to be expressed by epithelial cells involved in malignancy. In the present study, the transcriptional levels of S100A8 and S100A9 were investigated in various subtypes of breast cancer (BC), and the correlation with estrogen receptor 1 (ESR1) and GATA binding protein 3 (GATA3) gene expression was evaluated using microarray datasets. The expression of S100A8 and S100A9 in BC cells was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The regulation of ESR1 and GATA3 by administration of recombinant S100A8/A9 was examined in the BC MCF-7 cell line using quantitative (q)PCR. The association between S100A8 and S100A9 and overall survival (OS) was investigated in GeneChip(r) data of BC. The expression levels of S100A8 and S100A9 were higher in human epidermal growth factor receptor 2 (Her2)-amplified and basal-like BC. The messenger (m)RNA levels of S100A8 and S100A9 were inversely correlated with ESR1 and GATA3 expression. S100A8/A9 induced a 10-fold decrease in the mRNA levels of ESR1 in MCF-7 cells. Poor OS was associated with high expression levels of S100A9, but not with high expression levels of S100A8 in BC. In conclusion, strong expression and secretion of S100A8/A9 may be associated with the loss of estrogen receptor in BC, and may be involved in the poor prognosis of Her2+/basal-like subtypes of BC. PMID- 26998105 TI - Luteinizing hormone inhibits cisplatin-induced apoptosis in human epithelial ovarian cancer cells. AB - The elevation of Luteinizing hormone (LH) is commonly observed in epithelial ovarian cancer. This correlation suggests a causal relationship between LH and ovarian cancer. LH has been reported to inhibit apoptosis in ovarian cancer cells. Programmed cell death gene 6 (PDCD6), also known as apoptosis-linked gene 2, is an apoptotic mediator that is required for apoptosis to numerous death stimuli. Therefore, the aim of the present study was to determine whether PDCD6 may be induced by LH in ovarian cancer, and whether LH may affect the apoptosis through PDCD6. Flow cytometry was used to detect the effects of cisplatin on the induction of apoptosis by LH. PDCD6 expression was monitored by quantitative polymerase chain reaction and western blotting. The signaling transduction pathways were also investigated by western blotting. The present study demonstrated that LH reduced cisplatin-induced apoptosis in ovarian OVCAR-3 and SKOV-3 cancer cells. The results indicated that PDCD6 expression was inhibited by LH. In addition, the inhibition of PDCD6, induced by LH, was mediated through the activation of the phosphatidylinositol 3-kinase/protein kinase B and p44/42 mitogen-activated protein kinase transduction signaling pathways. The present results suggest that LH affects the sensitivity of ovarian cancer cells to chemotherapy, primarily by signaling to inhibit apoptosis and to additionally suppress PDCD6. PMID- 26998106 TI - Treatment of osteolytic solitary painful osseous metastases with radiofrequency ablation or cryoablation: A retrospective study by propensity analysis. AB - The present study aimed to measure the improvement in pain relief and quality of life in patients with osteolytic solitary painful bone metastasis treated by cryoablation (CA) or radiofrequency ablation (RFA). Fifty patients with solitary osteolytic painful bone metastases were retrospectively studied and selected by propensity analysis. Twenty-five patients underwent CA and the remaining twenty five underwent RFA. Pain relief, in terms of complete response (CR), the number of patients requiring analgesia and the changes in self-rated quality of life (QoL) were measured following the two treatments. Thirty-two percent of patients treated by CA experienced a CR at 12 weeks versus 20% of patients treated by RFA. The rate of CR increased significantly with respect to baseline only in the group treated by CA. In both groups there was a significant change in the partial response with respect to baseline (36% in the CA group vs. 44% in the RFA group). The recurrence rate in the CA and RFA groups was 12% and 8%, respectively. The reduction in narcotic medication requirements with respect to baseline was only significant in the group treated by CA. A significant improvement in self-rated QoL was observed in both groups. The present study seems to suggest that CA only significantly improves the rate of CR and decreases the requirement of narcotic medications. Both CA and RFA led to an improvement in the self-rated QoL of patients after the treatments. However, the results of the present study should be considered as preliminary and to serve as a framework around which future trials may be designed. PMID- 26998107 TI - Evaluation of the safety and efficacy of TRAIL and taurolidine use on human fibrosarcoma xenografts in vivo. AB - Fibrosarcomas are rare malignant soft tissue tumours that exhibit a poor response to current therapeutic regimens. Previously, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and taurolidine were observed to induce apoptosis synergistically in HT1080 human fibrosarcoma cells in vitro. Consequently, the present study aimed to assess the safety and efficacy of TRAIL in combination with taurolidine on the local growth of fibrosarcoma xenografts in vivo. HT1080 fibrosarcoma cells were inoculated subcutaneously into both flanks of 49 athymic nude mice in order to establish tumour xenografts. TRAIL and taurolidine were applied intraperitoneally at various single and cumulative treatment doses. After 12 days, the experiment was terminated and surviving animals were euthanised. Tumour progression was determined during and following treatment. To assess the potential toxic effects of the two compounds, the organs (lung, liver, kidney and heart) of all animals were examined histologically. The results revealed that combined treatment with TRAIL and taurolidine significantly inhibited the growth of HT1080 xenografts, whereas untreated animals had steadily increasing tumours. The most effective combination was TRAIL at 2 ug per application (cumulative dose, 16 ug) and taurolidine at 30/15 mg per application (cumulative dose, 180 mg), reducing the mean size of implanted xenografts to 10.9 mm2 following treatment (vs. 48.9 mm2 in the control group; P=0.0100). Despite distinct tumour mass reduction, the rate of mortality was significantly increased in animals treated with TRAIL and taurolidine in a taurolidine dose-dependent manner; however, histological examinations of relevant organs revealed no evidence of systemic toxicity (mean survival time, 7.9 days in the treated groups vs. 12 days in the control group; P<0.0010). In summary, whilst the combination of TRAIL and taurolidine synergistically inhibited the growth of fibrosarcoma xenografts in vivo, it was also accompanied by significantly increased mortality rate. Thus, although taurolidine is assumed to be a compound with an acceptable toxicity profile, and therefore increasingly used in clinical trials, the current findings raise concerns with regard to its safety and therapeutic index, and indicate the requirement for further detailed toxicity tests. PMID- 26998108 TI - Novel possibilities in the study of the salivary proteomic profile using SELDI TOF/MS technology. AB - There is currently an increasing interest in exploring human saliva to identify salivary diagnostic and prognostic biomarkers, since the collection of saliva is rapid, non-invasive and stress-free. Diagnostic tests on saliva are common and cost-effective, particularly for patients who need to monitor their hormone levels or the effectiveness of undergoing therapies. Furthermore, salivary diagnostics is ideal for surveillance studies and in situations where fast results and inexpensive technologies are required. The most important constituents of saliva are proteins, the expression levels of which may be modified due to variations of the cellular conditions. Therefore, the different profile of proteins detected in saliva, including their absence, presence or altered levels, is a potential biomarker of certain physiological and/or pathological conditions. A promising novel approach to study saliva is the global analysis of salivary proteins using proteomic techniques. In the present study, surface-enhanced laser desorption/ionization-time-of-flight/mass spectrometry (SELDI-TOF/MS), one of the most recent proteomic tools for the identification of novel biomarkers, is reviewed. In addition, the possible use of this technique in salivary proteomic studies is discussed, since SELDI technology combines the precision of matrix-assisted laser desorption/ionization-TOF/MS proteomic analysis and the high-throughput nature of protein array analysis. PMID- 26998109 TI - Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis. AB - Oral squamous cell carcinomas (OSCCs) are a growing problem in the world. The various existing treatments have not markedly improved the survival rate of patients with OSCC during the past three decades. Novel treatment strategies are required. Sex determining region Y-box 2 (SOX2) is a transcription factor that is involved in the maintenance of embryonic stem cell pluripotency and in multiple developmental processes. SOX2 expression was indicated to act as a prognostic factor in various types of tumors, including breast, colorectal, gastric and lung cancer and glioblastoma, and as a link between malignancy and stemness. Cancer stem cells (CSCs) may be responsible for the genesis, growth and metastatic spread of tumors. The poor survival outcomes for OSCC patients may be attributable to a poor selection of target cells for treatment, as current oral cancer therapies are generally aimed at the global mass of tumor. Therefore, the consideration that novel approaches to oral cancer may be targeted using SOX2 and CSCs appears reasonable. In order to better understand the oncogenic roles and the corresponding signal transduction pathways of the SOX2 protein, the present study emphasizes the role of SOX2 in OSCC, including the proteins associated with OSCC, and reviews the literature regarding the role of SOX2 in lymph node metastasis. The aim of the present study is to provide a reference for future studies that engage in research on the aforementioned subject. PMID- 26998110 TI - PKM2 and cancer: The function of PKM2 beyond glycolysis. AB - Metabolic reprogramming is a hallmark of cancer cells and is used by cancer cells for growth and survival. Pyruvate kinase muscle isozyme M2 (PKM2) is a limiting glycolytic enzyme that catalyzes the final step in glycolysis, which is key in tumor metabolism and growth. The present review discusses the expression and regulation of PKM2, and reports the dominant role that PKM2 plays in glycolysis to achieve the nutrient demands of cancer cell proliferation. In addition, the present study discusses the non-metabolic function of PKM2, and its role as a coactivator and protein kinase, which contributes to tumorigenesis. Furthermore, conflicting studies concerning the role of PKM2 as a therapeutic target are reviewed. The improved understanding of PKM2 may provide a noval approach for cancer treatment. PMID- 26998111 TI - High levels of class III beta-tubulin expression are associated with aggressive tumor features in breast cancer. AB - Overexpression of class III beta-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer. PMID- 26998112 TI - The correlation between DNMT1 and ERalpha expression and the methylation status of ERalpha, and its clinical significance in breast cancer. AB - The correlation between the expression of DNA methyltransferase-1 (DNMT1) and estrogen receptor alpha (ERalpha), as well as the methylation status of ERalpha, was analyzed to investigate the clinical significance of DNMT1 and ERalpha in breast cancer. Substance P immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were utilized to detect the protein and mRNA expression levels of DNMT1 and ERalpha in 112 breast cancer and 20 normal breast specimens. Methylation specific PCR was utilized to detect the methylation status of ERalpha in ERalpha-positive and -negative breast cancer specimens and 20 normal breast specimens. The results of the present study revealed that DNMT1 protein and mRNA levels were low in normal breast specimens (10.00 and 46.05%, respectively) and ERalpha-positive breast cancer specimens (15.00 and 48.68%, respectively), compared with increased levels in ERalpha-negative breast cancer specimens (81.11 and 88.89%, respectively; P<0.05). The methylation rate of ERalpha was highest in ERalpha-negative breast cancer specimens (86.11%) compared with normal breast specimens and ERalpha-positive breast cancer specimens (10.00 and 36.84%, respectively; P<0.05). Positive expression of ERalpha protein was observed to be associated with progesterone receptor expression (P<0.05), however, no such association was observed for age, menopause state, tumor size, number of positive nodes, Tumor-Node-Metastasis stage or tumor type (P>0.05). The protein and mRNA expression levels of DNMT1 were negatively correlated with ERalpha expression (P<0.05). DNMT1 expression was positively correlated with methylation of ERalpha (P<0.05), and was positively correlated with the methylation of CpG islands of ERalpha, indicating that the detection of DNMT1 expression may be significant for the diagnosis and typing of breast cancer. PMID- 26998113 TI - BCL9, a coactivator for Wnt/beta-catenin transcription, is targeted by miR-30c and is associated with prostate cancer progression. AB - B-cell lymphoma 9 (BCL9), a component of aberrantly activated Wnt signaling, is an important contributing factor to tumor progression. Our previous data indicated that downregulation of the tumor suppressor microRNA-30c (miR-30c) was a frequent pathogenetic event in prostate cancer (PCa). However, a functional link between miR-30c and BCL9/Wnt signaling, and their clinical and pathological significance in PCa, have not been well established. The present study demonstrated that miR-30c serves as a key negative regulator targeting BCL9 transcription in PCa cells. Ectopic expression of miR-30c was associated with reduced expression of Wnt pathway downstream targets, including c-Myc, cluster of differentiation 44 and sex determining region Y-box 9 in DU145 human PCa cells. Examination of clinical prostate specimens revealed higher levels of BCL9 expression in PCa compared with that in benign prostate tissues. After substantiating this finding by patient sample analysis, BCL9 expression or activity was observed to be closely correlated with PCa biochemical recurrence (BCR) and disease progression, whereas it was inversely associated with miR-30c. Furthermore, overexpression of BCL9 in PCa acted cooperatively with miR-30c low expression to predict earlier BCR in PCa. These findings indicate that inhibition of BCL9/Wnt signaling by miR-30c is important in the progression of PCa. Furthermore, the combined analysis of miR-30c and BCL9 may be valuable tool for prediction of BCR in PCa patients following radical prostatectomy. PMID- 26998114 TI - Laccase purified from Cerrena unicolor exerts antitumor activity against leukemic cells. AB - Chronic lymphocytic leukemia (CLL) is the most commonly observed adult hematological malignancy in Western countries. Despite the fact that recent improvements in CLL treatment have led to an increased percentage of complete remissions, CLL remains an incurable disease. Cerrena unicolor is a novel fungal source of highly active extracellular laccase (ex-LAC) that is currently used in industry. However, to the best of our knowledge, no reports regarding its anti leukemic activity have been published thus far. In the present study, it was hypothesized that C. unicolor ex-LAC may possess cytotoxic activity against leukemic cell lines and CLL primary cells. C. unicolor ex-LAC was separated using anion exchange chromatography on diethylaminoethyl cellulose-Sepharose and Sephadex G-50 columns. The cytotoxic effects of ex-LAC upon 24- and 48-h treatment on HL-60, Jurkat, RPMI 8226 and K562 cell lines, as well as CLL primary cells of nine patients with CLL, were evaluated using 2,3-bis-(2-methoxy-4-nitro 5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. Annexin V/propidium iodide staining of Jurkat cells treated with ex-LAC was used to investigate apoptosis via flow cytometry. Ex-LAC induced changes in Jurkat and RPMI 8226 cells, as visualized by fluorescence and scanning electron microscopy (SEM). The XTT assay revealed high cytotoxic rates following treatment with various concentrations of ex-LAC on all the cell lines and CLL primary cells analyzed, with a half maximal inhibitory concentration ranging from 0.4 to 1.1 ug/ml. Fluorescence microscopy and SEM observations additionally revealed apoptotic changes in Jurkat and RPMI 8226 cells treated with ex-LAC, compared with control cells. These results were in agreement with the apoptosis analysis of Jurkat cells on flow cytometry. In conclusion, C. unicolor ex-LAC was able to significantly induce cell apoptosis, and may represent a novel therapeutic agent for the treatment of various hematological neoplasms. PMID- 26998115 TI - Natural killer cells inhibit pulmonary metastasis of hepatocellular carcinoma in nude mice. AB - Natural killer (NK) cells have been demonstrated to inhibit tumor growth. However, the role of NK cells in the inhibition of hepatocellular carcinoma metastasis is not well understood. The present study aimed to investigate the roles that NK cells may serve in inhibiting hepatocellular carcinoma metastasis. The role of isolated NK cells in the inhibition, proliferation, migration and invasion of the hepatoma cell line, MHCC97-H, was examined in vitro. Additionally, the survival rate of NK cells labeled with carboxyfluorescein diacetate-succinimidyl ester was assessed in vivo. An orthotopic implantation model was used to evaluate the role of NK cells in suppressing MHCC97-H cells in vivo. The effect of interleukin (IL)-2 stimulation on the tumor-inhibitory role of the NK cells was measured indirectly by analyzing the expression of various NK cell receptors and activated NK cell markers. It was observed that the NK cells inhibited the proliferation, migration and invasion of the MHCC97-H cells in vitro. Furthermore, the NK cells demonstrated long-term survival in the livers of the nude mice, and inhibited lung metastasis of hepatocellular carcinoma in vivo. However, liver tumor growth was not inhibited by the NK cells. IL-2 was identified to enhance the tumor-inhibitory effect of NK cells. The present study concludes that IL-2 may enhance the antitumor activity of the NK cells, and thereby inhibit the metastases of hepatocellular carcinoma in mice. PMID- 26998116 TI - Distribution and significance of interstitial fibrosis and stroma-infiltrating B cells in tongue squamous cell carcinoma. AB - Inflammation and desmoplasia are frequently identified in the tumor microenvironment, and have been demonstrated to be effective modulators of malignant biological events. However, the mechanisms by which the inflammatory microenvironment and interstitial fibrosis interact with one another remain to be elucidated. The present study aimed to investigate the degree of inflammation and interstitial fibrosis in tongue squamous cell carcinoma (TSCC), and how this acts to affect the outcome of TSCC. Tissue samples from 93 cases of TSCC and paired tumor-adjacent non-neoplastic tongue epithelium, as well as 14 cases of epithelial dysplasia, were used. Interstitial collagen fibers were assessed using Masson's trichrome stain. Immunohistochemical identification of cancer-associated fibroblasts (CAFs) and stroma-infiltrating B cells was performed via detection of alpha-smooth muscle actin (SMA), vimentin, desmin and cluster of differentiation 19 (CD19). The clinicopathological significance and overall survival of the TSCC patients were statistically analyzed. Regularly distributed CAFs and CD19+ B cells were identified in the TSCC stroma, whereas no CAFs or CD19+ B cells were observed in epithelial dysplasia samples or paired tumor-adjacent non-neoplastic tongue epithelium samples. The distribution of interstitial collagen fibers and CAFs was closely associated with the tumor stage of the primary cancer, and high levels of CD19+ B cells together with low CAF infiltration were identified to be associated with favorable prognosis in TSCC. In conclusion, the inflammatory and interstitial fibrotic microenvironments coexist in TSCC, and each has specific effects on disease outcome, individually or perhaps collectively. However, it remains to be determined exactly how the microenvironments affect one another in TSCC. PMID- 26998117 TI - Giant and high-risk gastrointestinal stromal tumor in the abdomino-pelvic cavity: A case report. AB - Gastrointestinal stromal tumors (GISTs) are benign mesenchymal tumors of the gastrointestinal tract. The clinical presentations of patients with GIST are variable and may be non-specific. The current study reports the case of a 66-year old man that presented with a gradual enlargement of the abdomen, emaciation, hyperhidrosis and frequent and urgent micturition. A computed tomography (CT) scan of the abdomen revealed a large, heterogeneous, low density mass that occupied the entire abdomino-pelvic cavity. Magnetic resonance imaging (MRI) identified a high signal intensity on the T2 weighted image and an intermediate signal intensity on the T1 weighted image. A contrast enhanced CT scan and MRI demonstrated the uptake of contrast material. A biopsy revealed that the tumor was composed of spindle cells, and immunohistochemical analysis identified the presence of mast/stem cell growth factor receptors. Together, these results lead to a diagnosis of GIST. The clinical findings, imaging modalities and pathological studies suggested that the GIST was a large and high-risk tumor located in the abdomino-pelvic cavity. The final surgical results confirmed these findings. Following conservative treatment with imatnib (400 mg, daily) for 6 months, the tumor became smaller and was suitable for surgery, which the patient received in December 2014. The final surgery confirmed the high-risk GIST. Subsequent to the surgery, the patient was recommended to continue the use of imatnib with regular CT or MRI reexaminations every 3 months, which are planned to continue for 3 years. PMID- 26998118 TI - Short hairpin RNA silencing of TGF-betaRII and FZD-7 synergistically suppresses proliferation and metastasis of hepatocellular carcinoma cells. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional regulator of cell growth, apoptosis, differentiation and migration. The Wnt/beta-catenin signaling pathway has been implicated in a wide spectrum of diseases, including numerous cancers and degenerative disease. The aim of the present study was to investigate if simultaneous blocking of TGF-beta and Wnt/beta-catenin signaling pathways exerts synergistic anti-tumor effects on hepatocellular carcinoma (HCC) cells. Short hairpin (sh) RNA eukaryotic expression vectors, specific to TGF-beta receptor II (RII) and Frizzled receptor (FZD)-7, were constructed by gene recombination. The expression vectors were transfected into human HCC HepG2 and Huh-7 cells using Lipofectamine 2000 to investigate the synergistic effects between TGF-beta and Wnt/beta-catenin signaling pathways on HCC cell proliferation, invasion and migration and the cell-cycle distribution. Western blot analysis was used to identify the expression of beta-catenin, c-Myc and cyclin D1 in transfected cells to investigate the underlying mechanisms that cause TGF-beta and Wnt/beta-catenin signaling in HCC cells. shTGF-betaRII-c and shFZD-7-2 were selected as the most efficient plasmids. A cell growth assay and colony-forming assay consistently demonstrated that the proliferative activity of the co-transfected group was significantly decreased compared to the single transfected group. A wound healing invasion and migration assay demonstrated that co-transfection of shTGF-betaRII-c and shFZD-7-2 decreased the invasion and migration abilities of the cells compared with either single-transfected group. In addition, the present study demonstrated that the observed reduction in cell proliferation was due to the cells arresting at the G1 phase of the cell cycle, and the downregulation of beta-catenin, c-Myc and cyclin D1 impaired the proliferative and invasive abilities of the HCC cells. The present results demonstrate that simultaneous blocking of TGF-beta and Wnt/beta-catenin signaling by targeting TGF-betaRII and FZD-7 may inhibit the proliferation and metastasis of HCC cells more effectively compared with blocking either the TGF-beta or Wnt/beta-catenin pathway. PMID- 26998119 TI - Malignant peritoneal mesothelioma in a patient with intestinal fistula, incisional hernia and abdominal infection: A case report. AB - Malignant mesothelioma is a rare type of cancer, most commonly associated with exposure to asbestos. Mesothelioma of the peritoneum, the membrane lining the abdominal cavity, is extremely rare. The current study reports the case of a 60 year-old female who presented with intestinal fistula, recurrent incisional hernia and abdominal infection, with no history of asbestos exposure, and was diagnosed with clear cell MPM. Computed tomography scans of the abdomen revealed extensive small bowel adhesions and massive peritoneal effusion. Histological examination of biopsy specimens indicated a diagnosis of malignant peritoneal mesothelioma with clear cell morphology. A laparotomy was performed, with subsequent resection of the bowel with fistula. Follow-up examination performed at 1-year post-surgery revealed that the patient was alive and in generally good health. PMID- 26998120 TI - Simian virus 40 may be associated with developing malignant pleural mesothelioma. AB - Malignant pleural mesothelioma (MPM) is associated with a history of heavy, long term exposure to asbestos. However, MPM may also be associated with simian virus 40 (SV40), a polyomavirus. The association between SV40 and MPM remains unclear. The present study was conducted in order to investigate the proportion of SV40 presence in the histological specimens of Vietnamese patients with MPM. Histological specimens were obtained from 45 patients (19 men and 26 women) with MPM at the Pham Ngoc Thach Hospital in Ho Chi Minh City, Vietnam. The specimens were processed and examined in order to detect the presence of the SV40 large T antigen (SV40 Tag) expression using immunohistochemistry. Of the 45 patients, 23 (51%) were epithelioid, 7 (16%) were biphasic, 6 (13%) were sarcomatoid, 4 (9%) were desmoplastic, 4 (9%) were well-differentiated papillary and 1 (2%) was the anaplastic subtype. In total, 9/45 patients (20%) demonstrated SV40 Tag expression. The proportion of patients that demonstrated SV40 Tag expression was not significantly different between the epithelioid subtype and the other subtypes (22 vs. 18%; P=1.000) or between the patients with stage IV disease and other stages (20 vs. 20%; P=1.000). The median survival time was not significantly different between the patients with or without SV40 Tag expression (196 vs. 236 days, P=0.8949). In summary, a 5th of the Vietnamese patients with MPM were associated with infection with SV40. SV40 may be a potential cause of MPM in Vietnam and this potential association requires additional studies. PMID- 26998121 TI - Synchronous double primary malignancies of the liver and kidney: A case report. AB - A 42-year-old male patient was admitted to the Department of General Surgery of The First Affiliated Hospital of Henan University of Science and Technology (Luoyang, China) presenting with abdominal discomfort. Enhanced computed tomography of the abdomen revealed a 15.1*7.0-cm, enhanced, double-spherical, exogenous, solid tumor originating from the left lateral hepatic lobe, in addition to a 4.3*4.2-cm mass in the mid portion of the left kidney. Pre operative imaging analysis resulted in the diagnosis of double cancer, consisting of hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The patient subsequently underwent left hemihepatectomy and left nephrectomy. Histological examination confirmed that the tumor originating from the left lateral hepatic lobe was HCC, and the tumor arising from the mid portion of the left kidney was clear cell RCC (ccRCC). The post-operative follow-up was uneventful. To the best of our knowledge, the present case is the first of its kind to describe the resection of synchronous double cancer, consisting of primary HCC and ccRCC. PMID- 26998122 TI - Expression of cluster of differentiation 74 in gallbladder carcinoma and the correlation with epithelial growth factor receptor levels. AB - Cluster of differentiation 74 (CD74), a transmembrane glycoprotein, has been previously reported to be important in the pathogenesis of several cancers, including hematological malignancies and solid tumors. The present study analyzed the significance of CD74 in gallbladder carcinomas (GBCs) and indicated the correlation of CD74 expression with epithelial growth factor receptor levels. Immunohistochemistry (IHC) was used to examine the expression of CD74 in GBC and normal gallbladder tissues, and western blotting was used to investigate whether CD74 expression varied in well-, moderately- and poorly-differentiated tumors. The correlation between the expression of CD74 and epithelial growth factor receptor levels was studied using the Spearman's rank correlation coefficient. The results of the IHC analysis revealed that CD74 was not expressed in the normal gallbladder tissues, and the mean integrated optical density value of CD74 in the poorly-differentiated tissues was increased compared with that in the well and moderately-differentiated tissues. The results of the western blotting were consistent with the results of the IHC. The expression of CD74 was positively correlated with epithelial growth factor receptor levels (r=0.607; P<0.05). These results indicate that CD74 may be important in the progression of GBC. PMID- 26998123 TI - Study on the therapeutic effect of neural progenitor cells in mice of a glioma murine model. AB - Glioma is a common malignacy of the brain that affects elderly patients in particular. Despite treatment, however, the survival rate is 12 months. The aim of the present study was to examine the therapeutic effect of neural progenitor cells (NPCs) on a glioma murine model, and to determine the possible mechanism of action. A glioma murine model was constructed and the tumor volume and tumor growth rate were measured. The therapeutic effect of cell injection on the glioma mouse model mice was confirmed. The quantitative polymerase chain reaction method was used to detect the expression of proto-oncogene and tumor suppressor gene. Intracranial injection of NPCs was performed to determine cell apoptosis. Preliminary results showed the mechanism of cell therapy effect at the transcription and cellular level. Compared with the model group, the tumor volume of the mice of the cell therapy group was significantly reduced from the 6th to 8th week, and the tumor growth rate was downregulated. The mechanism of action identified that NPCs regulate gene expression in tumor tissues, increase the expression of tumor suppressor gene, downregulate the gene expression of tumor cells, and reverse the proto-oncogene and imbalance of gene expression in gliomas. In conclusion, the new type of cell injection method can regulate the proto-oncogene of tumor tissue and tumor suppressor gene, improve the function phenotype of the cell, and effectively improve the clinical symptoms of mice with gliomas. PMID- 26998124 TI - Curative effect of the recent photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer. AB - Advanced colorectal cancer has a high mortality rate and conventional treatments have poor therapeutic effects. The aim of the present study was to analyze the recent curative effect and adverse reaction of photofrin photodynamic adjuvant treatment on young patients with advanced colorectal cancer. A total of 23 patients with advanced colorectal cancer who had accepted semiconductor laser photodynamic adjuvant treatment were selected as the observation group. In addition, 30 patients who had accepted concurrent radiotherapy and chemotherapy during the same period served as the control group. The observation group received photofrin (2 mg/kg) intravenously in 100 ml of 5% glucose, followed by the introduction of the endoscopic optical fiber to deliver laser radiation with an intensity of 630 nm wavelength pulse power. After 2 days, necrotic tissues were removed and irradiation of the original or new tumor lesions was performed and necrotic tissues were removed. The total effective rate and survival time was higher and the length of hospital stay was shorter in the observation group in comparison with the control group. The differences were statistically significant (P<0.05). The number of patients in the control and observation groups with symptoms of hematochezia, change in bowel habit, intestinal stimulation and incomplete intestinal obstruction were reduced. Additionally, the reduced ratio of the observation group was significantly increased in comparison with the control group (P<0.05). The adverse reaction rate of the observation group was lower than that of the control group and this difference was also statistically significant (P<0.05). In conclusion, use of photodynamic treatment for young patients with advanced colorectal cancer can effectively improve the clinical symptoms and reduce complications. PMID- 26998125 TI - AGR2 is associated with gastric cancer progression and poor survival. AB - Anterior gradient protein 2 (AGR2) has been reported as a novel biomarker with a potential oncogenic role. However, its association with the prognosis and survival rate of gastric cancer (GC) has not yet been determined. Therefore, the present study aimed to examine the expression and prognostic significance of AGR2 in patients with GC. Immunohistochemistry was used to analyze AGR2 and cathepsin D (CTSD) protein expression in 436 clinicopathologically characterized GC cases and 92 noncancerous tissue samples. AGR2 and CTSD expression were both elevated in GC lesions compared with noncancerous tissues. In 204/436 (46.8%) GC patients, high expression of AGR2 was positively correlated with the expression of CTSD (r=0.577, P<0.01). Furthermore, several clinicopathological parameters were significantly associated with AGR2 expression level, including tumor size, depth of invasion and TNM stage (P<0.05). Using Kaplan-Meier survival analysis, it was determined that the mean survival time of patients with low levels of AGR2 expression was significantly longer than those with high ARG2 expression (in stages I, II and III; P<0.05). For stage IV disease, no significant difference in survival time was identified. Multivariate survival analysis demonstrated that AGR2 was an independent prognostic factor and was associated in the progression of GC. The findings of the present study indicate that AGR2 expression is significantly associated with location and size of GC, depth of invasion, TNM stage, lymphatic metastasis, vessel invasion, distant metastasis, Lauren's classification, high CTSD expression and poor prognosis. Thus, AGR2 may be a novel GC marker and may present a potential therapeutic target for GC. PMID- 26998126 TI - Effect of photodynamic therapy combined with torasemide on the expression of matrix metalloproteinase 2 and sodium-potassium-chloride cotransporter 1 in rat peritumoral edema and glioma. AB - Peritumoral edema is a key stage in the infiltration and recurrence of glioma. Photodynamic therapy (PDT) increases the extent of peritumoral edema, which leads to a decrease in the effectiveness of PDT in treating glioma. The present study evaluated the effects of PDT combined with torasemide on the levels of matrix metalloproteinase (MMP) 2 and sodium-potassium-chloride cotransporter (NKCC) 1 in peritumoral edema regions of rat glioma. Adult male Wistar rats were inoculated with rat glioma C6 cells, and the presence of glioma was confirmed using magnetic resonance imaging 7 days subsequent to injection. The rats were randomly assigned to 4 groups (n=15): Control group, the rats received no treatment; PDT group, the rats received PDT at 80 J/cm2 for 10 min; torasemide group, the rats received 5 mg/kg torasemide intraperitoneally; and PDT + torasemide group, the rats received 5 mg/kg torasemide intraperitoneally for 3 days following PDT at 80 J/cm2 for 10 min. A total of 5 rats from each group were sacrificed 21 days following injection and the peritumoral edema tissues were harvested. MMP2 and NKCC1 expression levels were detected in the tissues using immunohistochemistry and western blot analysis. The mRNA expression levels of MMP2 and NKCC1 were observed using reverse transcription-quantitative polymerase chain reaction. Peritumoral edema was measured using a wet-to-dry weight (W/D) ratio, and survival times of the remaining 10 rats in each group were evaluated. Compared with the control group, tumor growth was significantly suppressed in the PDT group and the survival time was prolonged through a reduction in the expression of MMP2 (P<0.05), and an increased W/D ratio resulted in significantly increased expression of NKCC1 (P<0.05). Compared with the PDT group, the expression of NKCC1 and the W/D ratio in the PDT + torasemide group were significantly decreased (P<0.05), while no significant difference was observed in the expression levels of MMP2. In conclusion, PDT combined with torasemide prolonged the survival time of rats by inhibiting the growth of glioma through a reduction in the expression of MMP2, and by reducing peritumoral edema through a reduction in the expression levels of NKCC1. PMID- 26998127 TI - Tree shrew as a new animal model for the study of lung cancer. AB - Animal models play a key role in identifying treatments for various types of cancer, including lung cancer. The aim of the present study was to develop a new animal model for lung cancer induction using tree shrews from the Yunnan region in China. Tree shrews are suitable for a full simulation of human disease because their structure, function and metabolism are adequately close to human. This animal may offer a new experimental animal model to be used in the study of lung cancer. In the present study, 80 healthy tree shrews were distributed in experimental and control groups. Animals in the experimental group received different concentrations of iodized oil suspension of 3-methylcholanthrene (3-MC) and diethylnitrosamine (DEN) while animals in the control groups received saline or lipiodol solvent via endotracheal instillation. In the 3rd, 5th, 7th, 9th and 11th weeks the body weights of the animals were measured and chest X-ray examinations were conducted. Pathological studies on the lung tissues were also performed and the pathological changes occurring in bronchial epithelium in all the groups were examined. Animals in the experimental group gradually lost their body weight. For tree shrews in the blank control and solvent control groups the survival rates were 100 and 80%, respectively while the survival rate for the experimental group was 0%. Results from the chest X-ray conducted on animals in the blank control and solvent control groups revealed no obvious abnormalities while in the experimental group high-density shadow spots within the perfusion sites were observed. Pathological studies performed on these high-density areas confirmed changes in the bronchial epithelium. In the experimental groups we also detected bronchial epithelial atypical hyperplasia, and apparent changes in carcinoma in situ. In conclusion, lung cancer was successfully induced in tree shrews by a one-time endotracheal introduction of iodized oil suspension of 3-MC and DEN. PMID- 26998128 TI - Treatment of liver cancer of middle and advanced stages using ultrasound-guided percutaneous ethanol injection combined with radiofrequency ablation: A clinical analysis. AB - Liver cancer is a malignancy of the digestive system and has a high morbidity and mortality rate. Local intervention has become a viable option in identifying liver treatment. The aim of the present study was to analyze the clinical effects of treating liver cancer in middle and advanced stages using ultrasound-guided percutaneous ethanol injection (PEI) in tumors combined with radiofrequency ablation (RFA). A total of 100 patients with stage III-IV liver cancers were selected to participate in the study. Patients were divided into groups. In group A, treatment was initiated with PEI and after 1-2 weeks RFA was applied while in group B treatment was initiated with RFA and after 1-2 weeks PEI was applied. Patients in group C received PEI and RFA simultaneously. The clinical effects in the 3 groups were compared after 6-month follow ups. The volume of tumor ablation necrosis in group A was significantly greater than that in the groups B and C, while the size was significantly smaller compared to groups B and C after ablation. For group A, the complete ablation rate was significantly higher than that in groups B and C, and the differences were statistically significant (P<0.05). Liver damage indices, including raising levels of glutamic-pyruvic transaminase and total bilirubin, were significantly decreased in group A (P<0.05). The survival rate in group A was also significantly higher than in groups B and C (P<0.05). In conclusion, for patients with liver cancer in middle and advanced stages, the treatment method using PEI followed by RFA was more beneficial in terms of improving the tumor ablation rate, alleviating liver damages and increasing survival rates. PMID- 26998129 TI - Ki-67 expression in luminal type breast cancer and its association with the clinicopathology of the cancer. AB - The aim of the present study was to examine Ki-67 expression in tissue of luminal type breast cancer and to investigate the association between the Ki-67 expression level and clinicopathology of breast cancer. A total of 62 patients with breast cancer were included in the study group, whereas 30 patients undergoing a health check-up who were diagnosed with breast hyperplasia were included in the control group. Levels of Ki-67 expression in patients of the two groups were assessed using fluorescent quantitative polymerase chain reaction. The association between Ki-67 and the clinicopathology of the cancer was investigated by analyzing cancer cell proliferation and migration by reducing Ki 67 expression in the human MCF-7 cancer cell line. Compared with the controls, Ki 67 expression was significantly increased in the serum and cancer tissue of breast cancer patients (P<0.05). Ki-67 mRNA expression was significantly higher in cancer tissue than that in the corresponding paracancerous tissue of breast cancer (P<0.05). In addition, a high expression of Ki-67 was positively correlated with the clinical staging of tumor, tumor size and lymphatic metastasis of breast cancer, with statistical significance (P<0.05). In MCF-7 cells with a reduced Ki-67 expression, the proliferation activity and migration of breast cancer cells were significantly reduced (P<0.05). In conclusion, Ki-67 may be involved in promoting the genesis and development of breast cancer by affecting the proliferation and migration of cancer cells. PMID- 26998130 TI - Prognostic significance of S-phase fractions in peritumoral invading zone analyzed by laser scanning cytometry in patients with high-grade glioma: A preliminary study. AB - The predominant characteristic of malignant glioma is the presence of invading tumor cells in the peritumoral zone. Distinguishing between tumor cells and normal cells in a peritumoral lesion is challenging. Therefore, the aim of the present study was to investigate the cell-cycle phase measurements of fixed paraffin-embedded specimens from the peritumoral invading zone of high-grade gliomas using laser scanning cytometry. A total of 12 high-grade gliomas (2 anaplastic astrocytomas and 10 glioblastomas) were studied. The tumor core and peritumoral invading zone of each tumor specimen were investigated. Tissue sections (50 um) from the paraffin blocks were deparaffinized, rehydrated and enzymatically disintegrated, and the cells in suspension were stained with propidium iodide and placed on microscope slides. A slight trend for an increased S-phase fraction in the peritumoral invading zone compared with the tumor core was observed (P=0.24). Additionally, there was a trend for a decrease in the overall survival time of patients with increasing peritumoral invading zone S phase fraction (P=0.12). These data suggest that laser scanning cytometry is a powerful and clinically relevant tool for the objective analysis of the cell cycle in malignant gliomas. PMID- 26998131 TI - Genetic alterations of HER genes in chromophobe renal cell carcinoma. AB - Chromophobe (ch) renal cell carcinoma (RCC) is the 3rd most common subtype of RCC and occurs in 5% of all RCCs. Although chRCC generally demonstrates more favorable outcomes compared with other subtypes of RCC, there is a 6-7% probability of tumor progression and metastasis in this disease. The subclassification of a more aggressive subtype of chRCC may be useful for the management of this cancer. The Erb-B2 receptor tyrosine kinase 2 [also known as human epidermal growth factor receptor (HER) 2] gene has been reported to be important in chRCC. The present study aimed to further investigate the abnormalities of the HER family genes and their potential association with chRCC. Fluorescence in situ hybridization was performed on 11 chRCC tissue specimens, and the Spearman's rank correlation coefficient analysis was used to assess the results. The loss of one copy of the HER2 and HER4 genes was observed to be the major alteration of the tumor cells in all chRCC cases. Statistical data indicated that loss of the HER2 gene was strongly correlated with loss of the HER4 gene (P=0.019). The findings of previous studies were also combined for analysis, and were consistent with those of the present study. In addition, the amplification of HER1 was also strongly correlated with the amplification of HER4 (P=0.004). Furthermore, a high percentage of genetic structural rearrangements was observed in HER3 genes, which was significantly associated with amplification of HER2 (P=0.005). Certain alterations in the HER gene family were also noted as a phenomenom in chRCC. Therefore, the characterization of the underlying aberrant functions of HER genes may be of interest for additional studies in the context of using HER genes to distinguish between RCC subtypes in order to establish improved treatment guidelines. PMID- 26998132 TI - A novel IGH@ gene rearrangement associated with CDKN2A/B deletion in young adult B-cell acute lymphoblastic leukemia. AB - Acquired copy number changes are common in acute leukemia. They are reported as recurrent amplifications or deletions (del), and may be indicative of involvement of oncogenes or tumor suppressor genes in acquired disease, as well as serving as potential biomarkers for prognosis or as targets for molecular therapy. The present study reported a gain of copy number of 14q13 to 14q32, leading to immunoglobulin heavy chain locus splitting in a young adult female. To the best of our knowledge, this rearrangement has not been previously reported in B-cell acute lymphoblastic leukemia (ALL). Low resolution banding cytogenetics performed at the time of diagnosis revealed a normal karyotype. However, retrospective application of fluorescence in situ hybridization (FISH) banding and locus specific FISH probes, as well as multiplex ligation-dependent probe amplification and high resolution array-comparative genomic hybridization, revealed previously hidden aberrations. Overall, a karyotype of 46, XX, del(9) (p21.3 p21.3),derivative(14) (pter-> q32.33:: q32.33-> q13 ::q32.33-> qter) was determined. The patient was treated according to the Polish Adult Leukemia Group protocol and achieved complete remission. The results of the present study indicate that a favorable prognosis is associated with these aberrations when the aforementioned treatment is administered. PMID- 26998134 TI - Inflammatory pseudotumor of the pineal region: First reported case. AB - Inflammatory pseudotumors originating in the central nervous system (CNS) are quite rare. To the best of our knowledge, the present study reports the first case of a inflammatory pseudotumor that developed in the pineal region, and describes the neuroimaging, morphological and immunohistochemical findings. A 53 year-old male presented with hearing loss that had been apparent for 1 year and blurred vision that had persisted for 10 months. Magnetic resonance imaging (MRI) demonstrated a homogeneously-enhanced mass in the pineal region and obstructive hydrocephalus. A pathological examination revealed that the lesion was comprised predominantly of spindled cells in a collagenous background, with dense infiltrates of small lymphocytes, plasma cells and uninucleated histiocytes. Immunopositivity for cluster of differentiation (CD)138 was noted. Immunohistochemical staining showed that the cells were immunonegative for glial fibrillary acidic protein, S-100, placental alkaline phosphatase, neurofilament and Pit-Oct-Unc class 5 homeobox 1. The Ki-67 labeling index was <5%. The lymphocytic infiltrates consisted of CD3- and CD43-positive T-cells, and CD20- and CD79A-positive B-cells. Plasma cells displayed polytypic reactivity for immunoglobulin kappa and lambda light chains. Based on the MRI and the morphological and immunohistochemical analysis, a diagnosis of an inflammatory pseudotumor was formed. The patient underwent a surgical resection of the tumor and currently has a good prognosis. PMID- 26998133 TI - Surgical management of isolated retroperitoneal Castleman's disease: A case report. AB - Castleman's disease (CD) is an uncommon, poorly understood lymphoproliferative disease. Retroperitoneal forms may present as either a unicentric or multicentric disease. The present study reports the case of a 36-year-old man who was referred to the First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China), for a detailed examination of an abdominal mass. The abdominal ultrasound and computed tomography scans revealed a solid mass localized in the region between segment 1 of the liver and the pancreas. An endosonography-guided fine-needle aspiration biopsy revealed chronic inflammation and lymphadenosis. The present study reports a rare case, in which the patient was treated with an exploratory laparotomy and resection. The retroperitoneal mass was pathologically diagnosed as CD of the hyaline vascular type. The patient was closely followed-up for 11 months and is presently free of disease. In conclusion, the possibility of unicentric CD should be considered when facing a solid hypervascular retroperitoneal mass. A complete surgical resection may successfully treat the disease without an unnecessarily extensive resection for the unicentric type. PMID- 26998135 TI - Synovial lipomatosis of the metatarsophalangeal joint: A case report. AB - Synovial lipomatosis, also termed lipoma arborescens, is an extremely rare disorder of the synovium that causes joint pain, swelling and effusion. To date, only a small number of cases have been reported in the literature. The current study presents the case of a 44-year-old male with repeated swelling of the metatarsophalangeal joints of the left hallux, which had persisted for ~3 years. The main clinical manifestations on presentation included multiple osseous lumps and limited activity of the left hallux without pain. Magnetic resonance imaging of the left hallux revealed a mass surrounding the left metatarsophalangeal joints. Subsequently, the lesion was resected. Pathological examination revealed well-defined lobules of mature adipocytes separated by thin fibrous septa, which indicated a diagnosis of synovial lipomatosis of the metatarsophalangeal joint of the left foot. The aim of this study was to evaluate synovial lipomatosis of the metatarsophalangeal joint, with an analysis of the clinical parameters and pathological features of the disorder. PMID- 26998136 TI - A case of myeloproliferative neoplasm with a normal complete blood cell count: A novel problem of the JAK2 era. AB - The present study reported a case of a myeloproliferative neoplasm (MPN) in a patient with a normal complete blood cell count. Bone marrow biopsy showed bone marrow hyperplasia, an elevated megakaryocyte count, megakaryocytic dysplasia and pleomorphic changes, multiple megakaryocyte clusters and focal reticulin fiber hyperplasia. Furthermore, genetic analysis revealed that the patient was positive for the JAK2-V617F mutation, and negative for the JAK2 exon 12 and 13 mutations and the BCR-ABL (p210) fusion gene. The patient's condition was basically stable and at the time of writing, the patient remained in a stable condition with no specific symptoms of disease. The present study also analyzed the diagnostic and clinical features of MPNs, and a literature review was performed. MPN with a normal complete blood cell count is a rare disease, and attention should be focused on this entity in the clinic. PMID- 26998137 TI - Small bowel adenocarcinoma arising in a patient with hereditary hemorrhagic telangiectasia: A case report. AB - Patients with hereditary hemorrhagic telangiectasia (HHT) are reportedly at a lower overall risk of malignancies, and small bowel adenocarcinoma (SBA) arising in a HHT patient is extremely rare. In this study, the case of a 37-year-old female with HHT who developed a poorly differentiated jejunal adenocarcinoma five years after ileocecal resection for multiple colonic adenomas is presented. The patient underwent curative resection of the cancer invading the ileum and the mesentery of the transverse colon, but had to overcome critical complications perioperatively, stemming from HHT-associated peripheral capillary dilatation and arteriovenous malformation, including nosebleeds and possible infusion-induced air embolism through pulmonary shunts. The patient subsequently received adjuvant chemotherapy including capecitabine and oxaliplatin for 6 months, and currently remains alive without any evidence of recurrence 12 months after the second surgery. This patient with SBA was an instructive case demonstrating the necessity of careful attention during major surgery in HHT. PMID- 26998138 TI - Epithelial membrane protein 1 expression in ovarian serous tumors. AB - The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity. PMID- 26998139 TI - Solanine-induced reactive oxygen species inhibit the growth of human hepatocellular carcinoma HepG2 cells. AB - The aim of the present study was to investigate the effect of solanine on promoting human hepatocellular carcinoma HepG2 cells to produce reactive oxygen species (ROS), and the molecular mechanisms leading to tumor cell apoptosis. Solanine was administered to HepG2 cells in vitro. A selection of probes targeting various cellular localizations of ROS were used to detect ROS expression using flow cytometry. The expression levels of apoptosis-associated proteins, including apoptosis signal-regulating kinase 1 (ASK1) and thioredoxin binding protein 2 (TBP-2), and proliferation-associated proteins, including histone deacetylase 1 (HDAC1), were detected using western blotting. The percentage of cells undergoing apoptosis was measured using an Annexin V fluorescein isothiocyanate/propidium iodide assay, and cell morphology was examined using Wright's stain followed by inverted microscopy analysis. ROS detection probes 2',7'-dichlorofluorescin diacetate and dihydrorhodamine 123 identified that abundant ROS, including hydroxyl radical (OH-) and hydrogen peroxide (H2O2), were produced in the cytoplasm and mitochondria of the solanine treated HepG2 cells compared with the control cells (P<0.05). Superoxide anion specific probes dihydroethidium and MitoSOXTM demonstrated that there were no significant alterations in the HepG2 cells following solanine treatment compared with the control cells (P>0.05). Western blotting results revealed that solanine upregulated the expression levels of ASK1 and TBP-2 and enhanced their kinase activities, whereas solanine decreased the expression level of the proliferation associated protein, HDAC1. The cell apoptotic rate was significantly increased (P<0.0001) in the solanine-treated HepG2 cells compared with the control cells. (P<0.05). Overall, the study indicated that solanine induces HepG2 cells to produce ROS, mainly OH- and H2O2, in a mitochondria-dependent and -independent manner. In addition, solanine stimulates the expression of ASK1 and TBP-2, and their kinase activities, but inhibits the expression of proliferation-associated proteins, such as HDAC1, thus contributing to HepG2 cell apoptosis. PMID- 26998140 TI - Small-lymphoid cells and myeloid antigen expression in a patient with IgG myeloma: A case report. AB - Multiple myeloma is defined as a malignant proliferation of a single clone of plasma cells resulting in monoclonal immunoglobulin production. Due to the number of plasma cell morphological variants, difficulty is often faced during morphological diagnosis. The current study describes the case of a 49-year-old woman presenting with atypical plasma cell morphology detected by a bone marrow examination. Flow cytometric immunophenotyping determined the nature of the neoplastic cells as monoclonal myeloma cells with myeloid antigen expression. Serum electrophoresis with immunofixation and subsequent clinical findings confirmed this diagnosis. Therefore, the immunophenotyping of plasma cells in myelomas may be useful for the diagnosis of cases with atypical plasma cell morphology. PMID- 26998141 TI - MicroRNA-711 is a prognostic factor for poor overall survival and has an oncogenic role in breast cancer. AB - MicroRNAs are important in cancer development and progression. In the present study, the clinical significance and function of microRNA-711 (miR-711) expression in breast cancer were investigated. The expression level of miR-711 was analyzed in breast cancer tissue samples using reverse transcription quantitative polymerase chain reaction. Cell proliferation, colony formation, apoptosis and Transwell assays were performed in breast cancer cell lines transfected with miR-711 mimics or inhibitors, or control sequence. miR-711 was found to be upregulated in 30 formalin-fixed paraffin-embedded breast cancer tissue samples compared with paired non-cancerous breast tissues (P<0.05). Furthermore, a higher miR-711 expression was demonstrated to be associated with poor overall and disease-free survival times in 161 breast cancer patients, and miR-711 was identified as an independent prognostic factor using multivariate Cox regression analysis. In vitro, overexpression of miR-711 resulted in a significant increase in proliferation, colony formation, migration and invasion of breast cancer cells. By contrast, downregulating miR-711 inhibited cell proliferation, colony formation, migration and invasion and enhanced the rate of apoptosis of breast cancer cells. To the best of our knowledge, the present study is the first to demonstrate that miR-711 is an independent prognostic factor and serves an important oncogenic function in breast cancer, suggesting that miR-711 is a potential biomarker of prognosis and a molecular therapeutic target in breast cancer. PMID- 26998142 TI - A retrospective review of 11 cases of villoglandular papillary adenocarcinoma of the uterine cervix and a review of the literature. AB - Villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix is a rare subtype of cervical adenocarcinoma (AC) that accounts for 3.7-4.8% of cervical AC. Compared with ordinary adenocarcinoma, VGPA is associated with a lower incidence, younger age and better prognosis. Treatment with fertility-preserving surgery is also possible. The present study analyzed cases treated in The Second Hospital of Jilin University (Changchun, Jilin, China) between January 2010 and December 2014. A total of 11 cases were selected; of these, 7 cases were pathologically confirmed. The remaining 4 cases were diagnosed as VGPA upon the pathological examination of the biopsy, but confirmed as another type of adenocarcinoma upon analysis of the surgical pathology. The median age of the patients whose pathology was confirmed post-operatively was 36 years, and all cases were positive for human papillomavirus (HPV). As all 7 patients had no requirement for further fertility, a radical hysterectomy was performed, with or without adjuvant therapy. The follow-up time ranged from 7-57 months, with a mean time of 29 months. There was no evidence of recurrence in any of the patients. All the patients remain alive to date. The results of the present study indicated that HPV infection is likely to be the cause of VGPA, and the prognosis of VGPA tends to be better compared with other types of adenocarcinoma. However, the number of studies that have reported cases of VGPA remains small, and all are retrospective analyses with short follow-up times. Therefore, physicians selecting treatment options for patients with VGPA should exercise caution. PMID- 26998143 TI - Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma. AB - The effects of dendritic cells (DCs) with low dose doxorubicin on the enhancement of the systemic immune response, including the effects on calreticulin (CRT) expression, heat shock protein 70 (HSP70) on the cell surface expression, and the enhancement of high mobility group box 1 (HMGB1) release from cancer cells, remain unclear. The present study investigated whether the combination of DCs and doxorubicin (ADM) induces immune cell death, and leads to tumor growth inhibition in a murine osteosarcoma model. To evaluate immune response activation in vivo, 4 groups of mice were established: i) untreated mice, ii) DC-treated mice, iii) ADM treated mice, and iv) DC and ADM-treated mice. Immunological cell death and CRT, HSP70, and HMGB1 expression levels were higher in doxorubicin-treated cells than those in untreated or those treated with DCs alone. NF-kappaB expression was higher in the DCs after ligand activation using CRT, HSP70, or HMGB1 in vitro. Mice treated with DCs and ADM displayed an increased number of CD8+ T-lymphocytes within metastatic tumors and inhibition of metastatic growth. The expression of CRT and the release of HMGB1 from tumor tissues were increased in the ADM-treated groups. Treatment with DCs and ADM resulted in the highest serum interferon-gamma levels. Combining ADM, which can induce immunogenic cell death, with DCs enhanced the systemic immune response. The findings of the present study provide further support for the continued development of antitumor agents that induce cell death and the immune response to target osteosarcoma. PMID- 26998144 TI - Gastric fistula secondary to drainage tube penetration: A report of a rare case. AB - Cases of gastric fistula secondary to drainage tube penetration have rarely been reported. The current study presents a case of gastric penetration caused by misplacement of a drainage tube after a splenectomy. The patient was admitted to the Department of Hepatobiliary Surgery, (Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, China) for blunt abdominal trauma due to injuries sustained in an automobile accident. A ruptured spleen was found and successfully removed surgically. On post-operative day 7, the patient complained of slight discomfort and tenderness in the left upper quadrant of the abdomen. In addition, 500 ml of bile-colored fluid with small food particles was noted in the drainage tube. Barium X-ray revealed a gastric fistula in the upper gastrointestinal tract. Gastroscopy indicated infiltration of the drainage tube into the gastric cavity. No significant peritoneal effusion was observed, as revealed by abdominal ultrasound examination. These results confirmed the diagnosis of a gastric fistula secondary to perforation by the drainage tube. Following conservative treatment with antibiotics and total parenteral nutrition, the general condition of the patient improved significantly. The drainage tube was withdrawn progressively, as the amount of fluid being discharged was decreasing. Gastroenterography confirmed perforation closure and the tube was finally removed on post-operative day 44. PMID- 26998145 TI - Primary kidney parenchyma squamous cell carcinoma mimicking xanthogranulomatous pyelonephritis: A case report. AB - Primary kidney parenchyma squamous cell carcinoma is extremely rare, and this is the forth case to be reported. In the present study, a case of a 61-year old man is discussed. The man presented with recurrent lumbago, gross hematuria for nearly 2 months, and suspicious inflammatory kidney diseases on contrast-enhanced computed tomography (CT) and fludeoxyglucose-positron emission tomography (FDG PET)/CT, but a tumor can not be excluded completely prior to surgery. Finally, radical nephrectomy was performed, and histological analysis determined that the diagnosis was kidney parenchyma squamous cell carcinoma with inflammation invasion. The present case highlights the potential confusion of preoperative diagnosis of renal tumor with inflammation, and introduces the potential role of FDG-PET in its diagnosis and survival evaluation in renal malignancies. PMID- 26998146 TI - Polymorphisms of glutathione S-transferase pi 1 and toll-like receptors 2 and 9: Association with breast cancer susceptibility. AB - Polymorphisms in antioxidant enzymes and innate immune receptors have been implicated in the development of various types of cancer. The present study aimed to investigate whether polymorphisms of glutathione S-transferase pi 1 (GSTP1) and toll-like receptors (TLRs) 2 and 9 are associated with susceptibility to breast cancer among females. The study was conducted on 72 Egyptian female patients with breast cancer, along with 100 healthy volunteers. Polymorphisms of GSTP1 (codon 105 Ile/Val) and TLR9 rs187084 (1237T/C) genes were assessed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, while the -196 to -174 deletion/insertion (del/ins) polymorphism of TLR2 was detected by PCR. The results indicated a decrease in GSTP1 Val allele frequency in breast cancer patients compared with healthy controls, at rates of 22.9 vs. 32.5%, respectively. In addition, the breast cancer group demonstrated a decreased TLR9 C allele frequency compared with the control group, at rates of 36.1 vs. 51.5%, respectively (P=0.0047). A non-significant difference was detected in the frequency of the TLR2 -196 to -174 del allele in breast cancer patients when compared to normal controls. In conclusion, these results suggested that the GSTP1 Val and TLR9 1237C alleles, but not TLR2 -196 to -174 del, are likely to be associated with breast cancer development among females. PMID- 26998147 TI - Plexiform fibromyxoma with cotyledon-like serosal growth: A case report of a rare gastric tumor and review of the literature. AB - Plexiform fibromyxoma is a rare, benign mesenchymal neoplasm that predilects the gastric antrum and has potential for misdiagnosis as a gastrointestinal stromal tumor (GIST). The histology of the tumor is characterized by interwoven fascicular growth of cytologically bland spindled cells within a variably myxoid stroma. The current study reports the clinicopathological and immunohistochemical findings of a plexiform fibromyxoma resected from a 28-year-old Vietnamese female. The patient presented with acute, severe abdominal pain and worsening anemia. The initial fine-needle aspiration and needle core biopsy of the gastric antral mass led to an initial diagnosis of GIST. The subsequent distal partial gastrectomy revealed a 5.5-cm transmural antral mass that ulcerated the overlying mucosa and grew as variably elongated, myxoedematous, polypoid (cotyledon-like) excrescences from the serosal surface. Microscopically, the tumor demonstrated plexiform and multinodular growth of cytologically bland spindled cells proliferating in an abundant myxocollagenous stroma with a prominent capillary network. Tumor cells immunohistochemically expressed smooth muscle actin and CD10, but did not express CD117, Discovered on GIST-1 or nuclear beta-catenin. Follow-up evaluation 23 months post surgery revealed no evidence of residual tumor. A review the cases of this rare entity reported in the English language literature is also provided. PMID- 26998148 TI - 18F-fluoroethyl-L-tyrosine positron emission tomography for the differential diagnosis of tumefactive multiple sclerosis versus glioma: A case report. AB - Large demyelinating inflammatory central nervous system (CNS) lesions may present with contrast enhancement on magnetic resonance imaging and may mimic CNS tumors such as glioma. In ambiguous cases, new diagnostic tools that may be helpful for distinguishing between demyelinating inflammatory and neoplastic CNS lesions are required. The current study presents the case of a patient with a large contrast enhanced frontal brain lesion, who was initially diagnosed with tumefactive multiple sclerosis. Following the progression of the brain lesion, an 18F fluoroethyl-L-tyrosine positron emission tomography (18F-FET PET) was performed, revealing markedly elevated static 18F-FET uptake parameters along with time activity-curves consistent with glioma. Subsequently, a biopsy was undertaken, which confirmed the presence of anaplastic oligoastrocytoma. This case illustrates that 18F-FET PET may provide useful diagnostic information in cases where distinction between neoplastic and demyelinating inflammatory CNS lesions is challenging. However, further systematic and prospective analyses are warranted to explore the value of this method in this setting. PMID- 26998149 TI - Development of a standardized flow cytometric method to conduct longitudinal analyses of intracellular CD3zeta expression in patients with head and neck cancer. AB - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common neoplasm in the world. The follow-up protocols currently available do not appear to diagnose treatment failures and recurrences early enough to provide the best treatment to improve the survival rates of patients. The identification of biomarkers may aid in diagnosing, monitoring the progression, or predicting treatment outcomes in HNSCC. The present study aimed to evaluate whether cluster of differentiation (CD) 3zeta chain expression may serve as a biomarker for the early detection of recurrent or persistent HNSCC. However, in a longitudinal study, a standardized method that allows consistent data comparisons in an inter assay manner is critical. The present study reveals a method to monitor expression levels of CD3zeta over multiple time-points using flow cytometry. The present study validated the use of an internal control and normalization procedure for tracking alterations in CD3zeta expression in samples from patients with HNSCC, which were collected and assayed for a longitudinal study. PMID- 26998150 TI - MicroRNA-497 suppresses osteosarcoma tumor growth in vitro and in vivo. AB - It has been demonstrated that microRNA-497 (miR-497) acts as a tumor suppressor and is involved in tumor progression, development and metastasis in several types of cancer. However, little is known about the exact role of miR-497 in osteosarcoma (OS). The aim of the current study was to investigate the potential role of miR-497 in human OS. The role of miR-497 in the growth and survival of OS cells was determined using several in vitro approaches and a nude mouse model. The results demonstrated that exogenous expression of miR-497 in human OS MG63 cells suppressed cell proliferation, colony formation, migration and invasion, and induced cell apoptosis and cell arrest at the G0/G1 phase of the cell cycle. In addition, the results of the in vivo study indicated that restoration of miR 497 inhibited OS tumor growth in a nude mouse model. Overall, the results of the present study identified a crucial tumor suppressive role of miR-497 in the progression of OS, and suggested that miR-497 may be a potential therapeutic agent for the treatment of OS. PMID- 26998151 TI - Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer. AB - The present study investigated the potential association between matrix metalloproteinase-9 (MMP-9) expression and the pathogenesis of bladder cancer. The present study reviewed previous studies published in Chinese and English using predefined selection criteria, which identified high-quality studies concerning MMP-9 and bladder cancer. Statistical analyses of the data were conducted using Comprehensive Meta-Analysis software version 2.0. In total, 23 case-control studies were selected, which consisted of 1,040 bladder cancer patients and 244 healthy controls. The expression rates and protein levels of MMP 9 were significantly increased in bladder cancer patients compared with the healthy controls, which was demonstrated using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay-based methods. Furthermore, the expression rate of MMP-9 in histological G1/G2 grade bladder cancer tumors was significantly decreased compared with G3 tumors. Subgroup analysis based on ethnicity demonstrated that the rate of MMP-9 protein expression between bladder cancer patients and healthy controls was significantly different in African, Asian and Caucasian patients, which was identified using IHC. The MMP-9 protein levels in bladder cancer patients and healthy controls were significantly different between Asian and Caucasian patients, but not African patients. The differences between MMP-9 expression in ethnic groups were also evident in the expression rate of MMP 9 identified in histological G1/G2 grade tumors in Asian and Caucasian patients compared with G3 grade tumors, which was not evident in African patients. In conclusion, the present meta-analysis results markedly indicate that MMP-9 expression is associated with clinicopathological features of bladder cancer, suggesting that MMP-9 may be a useful biomarker in the diagnosis and clinical management of bladder cancer, and may be a valuable therapeutic target. PMID- 26998152 TI - Upregulation of PREX2 promotes the proliferation and migration of hepatocellular carcinoma cells via PTEN-AKT signaling. AB - Phosphatidylinositol-3,4,5-trisphosphate Rac exchanger 2 (PREX2), a regulator of the small guanosine triphosphatase Rac, demonstrates an inhibitory effect on the activity of phosphatase and tensin homolog (PTEN). Previously, PREX2 was implicated in the regulation of cell invasion in hepatocellular carcinoma (HCC). However, the exact role of PREX2 in the regulation of HCC cell proliferation and migration, as well as the underlying mechanisms, remains unclear. In the present study, reverse transcription-quantitative polymerase chain reaction revealed that PREX2 was upregulated in HCC tissue compared with matched adjacent non-tumorous tissue. In addition, the present study demonstrated that the messenger RNA and protein levels of PREX2 increased in human HCC HepG2, LH86, LMH and PLHC-1 cell lines compared with normal human liver THLE-3 cells. Overexpression of PREX2 significantly enhanced the proliferation and migration of HCC cells, and knockdown of PREX2 expression significantly suppressed the proliferation and migration of HCC cells. Additional investigation revealed that overexpression of PREX2 suppressed the activity of PTEN, leading to an enhancement in the activity of protein kinase B (AKT). By contrast, knockdown of PREX2 expression upregulated the activity of PTEN and suppressed the activity of AKT. Overall, the present study suggests that PREX2 promotes the proliferation and migration of HCC cells by inhibiting PTEN-AKT signaling. PMID- 26998153 TI - Stereotactic radiotherapy for the treatment of lung cancer with a giant left atrial tumor thrombus: A case report and literature review. AB - Lung cancer presenting with a giant atrial tumor thrombus is particularly rare. Surgical resection, aided by a cardiopulmonary bypass, is the standard treatment of choice if there is no distant metastasis. However, this form of surgery carries a high risk, with the subsequent patient prognosis being extremely poor. The current study describes the case of a 52-year-old man presenting with left lung squamous cell carcinoma that had extended into the left atrium. The patient was treated with stereotactic radiotherapy, and regarding the atrial disease, a complete response was achieved within 12 months. The present case demonstrates that stereotactic radiotherapy may be a beneficial palliative treatment for patients with stage IV lung cancer invading the left atrium. PMID- 26998154 TI - Xp11.2 translocation renal cell carcinoma with multiple bone metastases: A case report. AB - Xp11.2 translocation/transcription factor enhancer 3 (TFE3) fusion gene associated with renal cell carcinoma (Xp11.2 translocation RCC) is rare and occurs predominantly in children and adolescents. The current study reports the case of a 14-year-old male with Xp11.2 translocation RCC, who presented with chest pain that had persisted for 1 month. A solid neoplasm was located in the left kidney of the patient. Contrast-enhanced computed tomography revealed the presence of a solid mass in the kidney, with uneven enhancement. Destruction of multiple bones was also observed. The patient was treated with a radical nephrectomy. The pathological examination of the tumor revealed that the tumor cells contained an eosinophilic cytoplasm in the renal interstitial tissue. Immunohistochemistry revealed that the tumor cells expressed P504S, cluster of differentiation 10, pan-cytokeratin, vimentin and TFE3. In conclusion, Xp11.2 translocation RCC is a rare type of kidney cancer. Diagnosing this disease prior to surgery is challenging, and providing a definite diagnosis requires histopathological and immunohistochemical examination, while genetic analysis may also be required. PMID- 26998155 TI - Giant non-functional parathyroid cyst: A case report. AB - Giant parathyroid cysts (PCs) are a rare entity and possess a benign clinical course. PCs may be functional or non-functional, depending on the ability of the cyst to secrete parathyroid hormone (PTH). The present study reports a rare case of a giant PC in a 56-year-old male who presented to the Affiliated Tumor Hospital, Zhengzhou University (Zhengzhou, Henan, China) with a 10-month history of exertional dyspnea, associated with mild dysphagia that had persisted for 3 months. The present study reviews the clinical situation, laboratory examination, radiographic findings, treatment and prognosis of the patient, and provides a brief discussion regarding the associated literature. Giant PCs may manifest with compressive symptoms of the surrounding tissues. The diagnosis of a giant PC is based on increased levels of PTH in the fluid collected during the aspiration of the cyst. Management by surgical excision is recommended for giant PCs that cause local cervical symptoms. PMID- 26998156 TI - Clinical significance of pre-operative neutrophil lymphocyte ratio and platelet lymphocyte ratio as prognostic factors for patients with colorectal cancer. AB - The present study aimed to investigate the independent prognostic values of the pre-operative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in patients with colorectal cancer (CRC). The present study retrospectively analyzed the data of 216 patients with CRC from a single hospital. The clinicopathological characteristics of the patients were compared and prognostic factors were evaluated. NLR and PLR were associated with tumor differentiation status and the tumor diameter, respectively, and PLR was also associated with the primary tumor classification (T classification). Furthermore, NLR and PLR were positively associated with each other (R2=0.5368; P<0.0001). Univariate analyses indicated that stage II and III patients with a high NLR (>=4.98; P<0.001) or PLR (>=246.36; P<0.001) possessed a significantly poorer 5-year OS rate compared with those with a low NLR or PLR. Post-operative adjuvant chemotherapy improved the 5 year OS rate in patients with a high NLR or PLR. Multivariate analyses indicated that NLR and PLR were independent prognostic factors [NLR, relative risk (RR)=4.074 and P<0.001; PLR, RR=2.029 and P=0.029] in patients with CRC, and were associated with the T classification, lymph node metastasis and post-operative adjuvant chemotherapy response of patients. Additionally, the area under the curve (AUC) was 0.748 for NLR (95% CI, 0.684-0.804; P<0.0001) and 0.690 for PLR (95% CI, 0.623-0.751; P<0.0001). The RR and AUC indicated that NLR was the superior predictive factor in patients with CRC. In conclusion, the pre-operative NLR and PLR were significant independent prognostic factors in patients with CRC, and NLR was more effective as a prognostic marker compared with PLR. Adjuvant chemotherapy appeared to be more effective in CRC patients with a higher NLR or PLR. PMID- 26998157 TI - Prognostic factors analysis in EGFR mutation-positive non-small cell lung cancer with brain metastases treated with whole brain-radiotherapy and EGFR-tyrosine kinase inhibitors. AB - The survival time of non-small cell lung cancer (NSCLC) patients with brain metastases has been previously reported to be 6.5-10.0 months, even with systematic treatment. Patients that possess a certain epidermal growth factor receptor (EGFR) mutation alongside NSCLC with brain metastases also have a short survival rate, and a reliable prognostic model for these patients demonstrates a strong correlation between the outcome and treatment recommendations. The Cox proportional hazards regression and classification tree models were used to explore the prognostic factors in EGFR mutation-positive NSCLC patients with brain metastases following whole-brain radiation therapy (WBRT) and EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. A total of 66 EGFR mutation-positive NSCLC patients with brain metastases were retrospectively reviewed. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. The classification tree model was applied in order to identify prognostic groups of the patients. In the survival analysis, age, carcinoembryonic antigen (CEA) and status of the primary tumor were prognostic factors for progression free survival (P=0.006, 0.014 and 0.005, respectively) and overall survival (P=0.009, 0.013 and 0.009, respectively). The classification tree model was subsequently applied, which revealed 3 patient groups with significantly different survival times: Group I, age <65 years and CEA <=10 ug/ml; Group II, age <65 years and CEA >10 ug/ml or age >=65 years and CEA <=10 ug/ml; and Group III, age >=65 years and CEA >10 ug/ml. The major prognostic predictors for EGFR mutation-positive NSCLC patients with brain metastases following WBRT and EGFR-TKI were age and CEA. In addition, primary tumor control may be important for predicting survival. PMID- 26998158 TI - Bortezomib-induced severe pulmonary complications in multiple myeloma: A case report and literature review. AB - The proteasome inhibitor bortezomib is indicated for use in the treatment of multiple myeloma (MM) patients. The most common side effects are neurological and gastrointestinal, while severe pulmonary complications are rarely described. The present study reports the case of a 62-year-old man with immunoglobulin (Ig)G type MM who was treated with bortezomib, thalidomide and dexamethasone. Subsequent to the administration of chemotherapy, the patient developed an acute respiratory distress syndrome. High-resolution computed tomography of the chest showed bilateral diffuse alveolar infiltrations and multiple subpleural lesions. A diagnosis of bortezomib-induced severe pulmonary complications was formed. Systemic corticosteroid therapy led to a rapid improvement in clinical conditions and radiological findings. In addition, the present study reviewed the characteristics, including medical history, clinical manifestations, treatment strategies and outcomes, of all 16 MM patients with bortezomib-induced severe pulmonary complications reported previously in Pubmed. It was indicated that patients who were male, of IgG type, with a relapse status and a previous history of auto-PBSCT had a higher possibility of developing bortezomib-induced severe pulmonary complications. Additionally, a relatively low dose rather than a high dose of corticosteroids could obtain a better outcome. PMID- 26998159 TI - Serum sRANKL and sRANKL/OPG ratio: Novel biomarkers in non-small cell lung cancer. AB - Osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) are bone-regulating molecules. The two molecules have each been indicated to be involved in carcinogenesis. However, the diagnostic significance in non-small cell lung cancer (NSCLC) remains to be investigated. Thus, the objective of the present study was to investigate the serum levels of OPG and sRANKL in NSCLC patients, and to analyze their clinical significance. Serum OPG and sRANKL levels were determined in 50 patients with NSCLC, matched with 25 patients with benign lung nodule and 25 healthy controls by enzyme-linked immunosorbent assay. The level of serum sRANKL and the sRANKL/OPG ratio were significant elevated in the patients with NSCLC compared with the benign lung nodule patients and the healthy controls. Receiver operating characteristic curves were used to evaluate the performance of sRANKL and sRANKL/OPG. When the cut-off values for the sRANKL level and the sRANKL/OPG ratio were set at 4.20 pmol/l and 0.60, respectively, the sensitivity, specificity and accuracy of sRANKL were 74.0, 84.0 and 77.3%, respectively. Moreover, the sensitivity, specificity and accuracy of the sRANKL/OPG ratio were 84.0, 88.0 and 85.3%, respectively. On the other hand, when the cut-off values of the serum sRANKL level and the sRANKL/OPG ratio were set at 5.24 pmol/l and 0.63, respectively, the sensitivity, specificity and accuracy of sRANKL were 60.0, 84.0 and 68.0%, respectively. The sensitivity, specificity and accuracy of the ratio were 78.0, 64.0 and 73.3%, respectively. The OPG/RANKL system may be involved in the pathogenesis of NSCLC. More importantly, the serum sRANKL level and the sRANKL/OPG ratio may have the potential to be novel biomarkers for the diagnosis of NSCLC. PMID- 26998160 TI - Effect of synchronous solitary bone metastasectomy and lung cancer resection on non-small cell lung cancer patients. AB - Lung cancer is the most frequent cause of cancer-associated mortality among men and women globally. The skeleton is one of the most common metastatic sites. The majority of patients exhibiting bone metastases are treated using systemic therapy or symptom-based palliative approaches without surgery. The present study attempted to improve the therapeutic effects of synchronous surgeries in resectable non-small cell lung cancer patients exhibiting solitary bone metastasis. A total of 5 patients underwent synchronous lung cancer resections and solitary bone metastasectomies between October 2009 and November 2011 in the Department of Cardiothoracic Surgery, Shanghai Sixth People's Hospital (Shanghai, China). All patients had received fluorodeoxyglucose positron emission tomography computed tomography or bone scintigraphy to demonstrate the presence of solitary bone metastasis and to exclude the presence of metastases at alternative sites. The patients received standard lung cancer and mediastinal lymph node resections. In addition, bone lesions were assessed by orthopedists and operated on synchronously with standard procedures. Following surgery, all patients were administered standard chemotherapeutic regimens. Perioperative indicators, including time for thoracic drainage, length of hospital stay, incidence of post operative complications and progression-free survival (PFS) time, were observed. The average time for post-operative drainage was 4.6+/-1.1 days, and the average length of post-operative hospitalization was 8.8+/-2.2 days. All procedures were performed safely with no serious complications. The PFS of the patients was 13.2+/-7.7 months. While 2 patients presenting with spinal metastases succumbed at ~1 year post-surgery, the remaining 3 patients presenting with limb bone metastases survived for >16 months post-surgery, and were alive at the last follow-up. In conclusion, the present study indicated that a synchronous metastasectomy and lung tumor resection is a safe method of treatment. The PFS time and survival results demonstrated that on the rare occasion that a patient exhibits solitary bone metastasis, aggressive surgical treatment may be a potential therapeutic option. PMID- 26998161 TI - Expression and clinical significance of Beclin-1 in gastric cancer tissues of various clinical stages. AB - Autophagy is a common phenomenon in cancer metabolism. However the mechanism and guiding significance of autophagy in the development of gastric cancer has remained to be elucidated. In the present study, 75 gastric cancer tissue specimens were collected at The China Japan Union Hospital of Jilin University (Changchun, China). Of these samples, 16 cases were stage 1, 40 stage 2 and 19 stage 3. Polymerase chain reaction and western blotting were used to detect the messenger RNA and protein expression of Beclin-1, a significant protein associated with cellular autophagy. It was found that expression of Beclin-1 in cancer tissues from stages 1 and 2 was higher, while in stage 3 cases levels were significantly lower than that of adjacent normal tissues. In addition, the infiltration of inflammatory cytokines was also increased in stage 1 and 2 cases. In vitro studies revealed that following stimulation with interferon-gamma (IFN gamma), autophagy-associated proteins Beclin-1 and microtubule-associated protein light chain 3 were activated. Furthermore, activation of autophagy inhibited xenograft growth in nude mice. The results of these in vivo and in vitro experiments indicated that in gastric cancer tissues, autophagy was downregulated following the development of cancer tissue and that inflammation may be a significant factor in this process. IFN-gamma may be involved in the mediation of this process and thus present a novel target for the treatment of gastric cancer. PMID- 26998162 TI - Thickness of preperitoneal fat as a predictor of malignancy in overweight and obese women with endometrial polyps. AB - The aim of the present study was to determine the association between the thickness of preperitoneal fat (PFT), utilized as an indicator of visceral fat deposition, and the risk of premalignant and malignant changes of endometrial polyps (EPs) in overweight and obese women. Overweight and obese women who had undergone diagnostic outpatient hysteroscopy and subsequent endometrial polypectomy between January 2010 and May 2013 were analyzed. Each patient underwent a transabdominal ultrasound for the purpose of measuring the thickness of preperitoneal fat. A total of 146 overweight or obese women were analyzed. The overall incidence of malignant or premalignant lesions was 8.2%. Notably, 5 patients (3.4%) received a histopathological diagnosis of complex hyperplasia with atypia, while polyps harboring carcinoma were diagnosed in 7 cases (4.8%). A significantly increased PFT was observed in women exhibiting preneoplastic and neoplastic lesions, compared with women with benign EPs (mean +/- SD, 23.2+/-3.7 vs. 15.9+/-8.3; P<0.01). Patient age of >60 years was significantly associated with malignant progression of EPs, while body mass index, menopausal status, arterial hypertension, diabetes, abnormal uterine bleeding, hormone replacement therapy and tamoxifen treatment demonstrated no significant association with the development of preneoplastic and neoplastic lesions of the endometrium. In a multivariate analysis, only PFT maintained a significant correlation with the diagnosis of preneoplastic and neoplastic lesions on EPs (odds ratio, 1.14; 95% confidence interval, 1.04-1.26). Ultrasound evaluation of PFT in overweight and obese women may be useful for the identification of a particularly high-risk subgroup of women. Therefore, regardless of symptoms or additional clinical variables, these particularly high-risk women require appropriate counseling and prompt surgical removal of EPs. PMID- 26998163 TI - Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas. AB - The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I-IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors. PMID- 26998164 TI - Effect of CD38 on the multidrug resistance of human chronic myelogenous leukemia K562 cells to doxorubicin. AB - Drug resistance is a serious challenge in cancer chemotherapy. Alterations in the intracellular concentration and homeostasis of calcium (Ca2+) may contribute to the development of drug resistance. To investigate the mechanism of drug resistance in leukemia, the present study rendered human chronic myelogenous leukemia K562 cells resistant to the cytotoxic effect of doxorubicin by progressively adapting the sensitive parental K562 cells to doxorubicin. The resulting cells were termed K562/DOX. Subsequently, the expression of two multidrug resistance proteins, P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1), was analyzed in K562/DOX cells. In addition to P-gp and MRP1, these cells also expressed cluster of differentiation (CD)38 and its active enzyme adenosine diphosphate (ADP)-ribosyl cyclase. The present study also demonstrated that K562/DOX cells responded to cyclic ADP-ribose-mediated increases in intracellular Ca2+. These data indicate that CD38 may participate in the development of drug resistance to doxorubicin in K562 cells. PMID- 26998165 TI - Bradycardia as a rare symptom of cisplatin cardiotoxicity: A case report. AB - Cisplatin (DDP) is one of the most frequently used chemotherapeutic agents, and has a characteristic toxicity profile. For DDP, complications affecting the cardiovascular system, which are typical for certain other agents, are rare; however, their occurrence may lead to life-threatening conditions. To the best of our knowledge, there are few reported cases of DDP-induced bradycardia in the relevant medical literature. The current report presents the case of a 58-year old patient diagnosed with metastatic neuroendocrine carcinoma with a primary lesion in the posterior mediastinum, who was treated with DDP and etoposide chemotherapy. Following the initial chemotherapy cycle, the patient experienced severe symptomatic bradycardia (a drop in heart rate to 40 bpm), with the corrected QT interval prolonged to 424 msec. The patient's condition required close monitoring and treatment. Similar symptoms occurred following each of the three cycles of chemotherapy. Imaging studies performed following the third treatment cycle revealed disease progression, and the patient was referred for palliative care. Reports have indicated that damage to the cardiovascular system, including cardiac ischemia, diastolic disturbances, hypertension and microalbuminuria, may be associated with DDP-based therapy. However, the mechanism of DDP-associated cardiac toxicity remains to be elucidated. It may be induced by factors including direct toxicity, ion imbalance, heart infiltration and, in the case of neuroendocrine tumors, the influence of tumor excretions. PMID- 26998166 TI - High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma. AB - Ubiquitin-conjugating enzyme E2C (UBE2C) is a key regulator of cell cycle progression and is involved in the tumorigenesis of a variety of cancers. Previous studies have demonstrated that UBE2C is an important factor in the malignant progression of astrocytic tumors. However, the association between UBE2C expression and clinical prognosis of glioma patients has not been defined. In the present study, the expression of UBE2C in gliomas and non-cancerous brain tissues were detected by microarray and immunohistochemical analysis. The association between UBE2C expression and clinicopathological characteristics of the glioma patients was evaluated. The Kaplan-Meier method and multivariate Cox's proportional hazards model were used to analyze the survival time of the patients. The results demonstrated that the expression levels of UBE2C in anaplastic gliomas and glioblastoma (GBM) patients were significantly higher compared to low-grade gliomas, in microarray and immunohistochemistry analysis. A higher UBE2C expression was associated with a significantly decreased overall survival time in patients possessing anaplastic gliomas (P<0.01) and GBMs (P<0.05). Multivariate analysis of 80 GBM patients revealed that UBE2C expression was an independent prognostic factor. To the best of our knowledge, the present data suggest for the first time that UBE2C overexpression is strongly associated with an aggressive progression and poor outcome of malignant glioma. Therefore, UBE2C overexpression may be used as a predictor of poor prognosis in patients with malignant glioma. PMID- 26998167 TI - Telomere length assessment in leukocytes presents potential diagnostic value in patients with breast cancer. AB - Telomere shortening is associated with cancer development, primarily through the induction of genomic instability. The majority of studies have indicated that individuals with shorter blood telomeres may be at a higher risk of developing various types of cancer. There is increasing evidence that the study of the alterations in telomere length may improve cancer prognosis. The aim of the present study was to verify the use of telomere length parameters in the diagnostics of breast cancer stage. Telomere length was analyzed in the blood leukocytes of 52 patients with breast cancer relative to 47 control subjects using quantitative polymerase chain reaction. The effects of stage, grade, estrogen receptor, progesterone receptor and human epidermal growth factor 2 (HER2) status were assessed. The current study demonstrated that the average telomeric sequence length was significantly shorter in leukocytes from individuals diagnosed with a more severe stage of breast cancer (T2N1M0) than in leukocytes in the early stages of the disease (T1N0M0) (P=0.0207). Furthermore, the data indicated that telomeres in leukocytes derived from patients with HER2+ breast cancer were significantly longer compared with those with the HER2- type (P=0.0347). These results suggest that the assessment of telomeres in blood leukocytes may, at least partially, correspond with breast cancer staging and HER2 receptor status. PMID- 26998168 TI - Bortezomib-based chemotherapy to treat refractory angioimmunoblastic T-cell lymphoma: A case report and review of the literature. AB - The peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive neoplasms that account for <15% of all non-Hodgkin's lymphoma cases in adults. Angioimmunoblastic T-cell lymphoma (AITL) is a specific subtype of PTCL. The tumor is frequently aggressive and there is currently no general consensus regarding an effective treatment strategy. The present study reports a case in which bortezomib combined with dexamethasone was used to treat refractory AITL. A 63-year-old woman was admitted to Sir Run Run Shaw Hospital, Zhejiang University School of Medicine (Zhejiang, China) on August 17, 2013. The patient had been diagnosed with AITL for 4 months and had experienced a relapse of symptoms for the 4 days prior to admission. The patient demonstrated fever and dyspnea, accompanied by severe edema in the face and lower limbs, which later spread to the right upper limb. The patient was treated with bortezomib plus dexamethasone, which rapidly relieved the symptoms. The patient was subsequently administered an additional 2 cycles of bortezomib-based chemotherapy and survived for an additional 4 months, prior to succumbing to the disease. Only a small number of studies have reported the use of bortezomib in the treatment of T-cell lymphoma. The present study suggested that bortezomib-based treatment may be a reliable, safe and effective alternative for the treatment of relapsed/refractory PTCL. The efficacy of bortezomib as a treatment for PTCL requires additional evaluation in future studies. PMID- 26998169 TI - Computed tomography and magnetic resonance imaging findings of intrasellar schwannoma: A case report and literature review. AB - Intrasellar schwannoma is extremely rare, and only a few cases have been reported in the literature to date. In the present study, the clinical, radiological and pathological features of a 50-year-old male patient with primary intrasellar schwannoma are presented. The patient presented with decreased visual acuity, and a subsequent computed tomography (CT) scan revealed a giant well-demarcated intrasellar mass with suprasellar extension, without cavernous sinus invasion. The lesion was slightly hyperdense with heterogeneous enhancement. On magnetic resonance imaging (MRI), the mass was isointense on T1 weighted images (WI), and slightly hyperintense on T2WI, with significant heterogeneous enhancement. Previous literature was reviewed to summarize the CT and MRI characteristics of intrasellar schwannoma. Despite the rarity of this tumor, intrasellar schwannoma must be included in the differential diagnosis of intrasellar lesions. PMID- 26998170 TI - Prognostic analysis of triple-negative breast cancer patients treated with adjuvant chemotherapy of fluorouracil, epirubicin and cyclophosphamide. AB - The aim of the present study was to investigate the association between the clinicopathological and demographic factors, and the survival time of patients with triple-negative breast cancer (TNBC) in China. The patients had received adjuvant chemotherapy consisting of 5-fluorouracil, epirubicin and cyclophosphamide (FEC; 500 mg/m2 cyclophosphamide, day 1; 75 mg/m2 epirubicin, day 1; 500 mg/m2 5-fluorouracil, days 1 and 8; every 3 weeks, for at least 4 cycles). The clinicopathological and demographic factors affecting the outcome of the patients with TNBC that received adjuvant FEC chemotherapy were evaluated. Within these variables, the overall survival (OS) and disease-free survival (DFS) times were analyzed using the log-rank test, which was constructed using the multivariate Cox proportional hazards regression model and Kaplan-Meier analysis. Additionally, Spearman's chi2 test was used to analyze categorical variables. In the univariate statistical analysis, the significant risk factors for TNBC patient survival were the stage of disease and lymph node status, which were associated with the OS and DFS, and the total number of pregnancies, which was associated with the DFS. In the multivariate Cox proportional hazard model, lymph node status was an independent prognostic indicator of OS [P<0.001; hazard ratio (HR), 1.996; 95% confidence interval (CI), 1.465-2.720] and DFS (P<0.001; HR, 1.824; 95% CI, 1.315-2.531). By the Kaplan-Meier method, the stage of disease and lymph node status demonstrated a significant effect on OS and DFS. Patients with the lymph node status N3 and stage III disease possessed a poor prognosis and survival. An association between lymph node status and the tumor recurrence and mortality rate was identified. The area under the curves of the lymph node status for TNBC recurrence and mortality were 0.676 (P=0.002) and 0.685 (P=0.001), respectively. Additionally, the number of pregnancies was associated with tumor size, lymph node status and stages of disease. Lymph node status is an independent prognostic indicator of OS and DFS to TNBC patients with FEC adjuvant chemotherapy. PMID- 26998171 TI - Lipid-poor renal angiomyolipoma: Differentiation from clear cell renal cell carcinoma using wash-in and washout characteristics on contrast-enhanced computed tomography. AB - In the present study, a total of 82 patients (42 men and 40 women; age range, 24 84 years), including 34 patients with lipid-poor renal angiomyolipoma (AML) and 49 with clear cell renal cell carcinoma (RCC), who had undergone multiphase contrast-enhanced computed tomography (CT) (i.e., CT with unenhanced, corticomedullary, nephrographic and 5-min delay phase scanning) were evaluated. The peak enhancement attenuation value, net enhancement attenuation value, enhancement ratio, washout value and washout ratio were calculated to compare the enhancement characteristics between the two diseases. The results revealed that the lipid-poor AMLs had a significantly higher mean attenuation value compared with that of CCRCCs on unenhanced CT scans (37.8 vs. 30.9 HU; Mann-Whitney U test, P=0.003). In addition, significant differences were found between lipid poor AMLs and CCRCCs with regard to wash-in (Mann-Whitney U test, P=0.001) and enhancement ratios (Mann-Whitney U test, P=0.010) on contrast-enhanced CT scans. A receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.722 using wash-in for differentiation between CCRCCs and lipid poor AMLs. Lipid-poor AMLs exhibited a reduced washout of contrast enhancement (35.8+/-32.7 HU washout value; 29.4+/-0.187% washout ratio) compared with that of CCRCCs (48.3+/-28.4 HU washout value; 35.7+/-0.148% washout ratio; Mann-Whitney U test, P=0.037 and P=0.204, respectively). The ROC analysis result yielded an AUC of 0.639 for the use of washout to differentiate CCRCCs from lipid-poor AMLs. In summary, a larger wash-in and washout of contrast enhancement is a predictor that a lesion is CCRCC. PMID- 26998172 TI - Best Practice BioBanking of Human Heart Tissue. AB - This review provides a guide to researchers who wish to establish a biobank. It also gives practical advice to investigators seeking access to samples of healthy or diseased human hearts. We begin with a brief history of the Sydney Heart Bank (SHB) from when it began in 1989, including the pivotal role played by the late Victor Chang. We discuss our standard operating procedures for tissue collection which include cryopreservation and the quality assurance needed to maintain the long-term molecular and cellular integrity of the samples. The SHB now contains about 16,000 heart samples derived from over 450 patients who underwent isotopic heart transplant procedures and from over 100 healthy organ donors. These enable us to provide samples from a wide range of categories of heart failure. So far, we have delivered heart samples to more than 50 laboratories over two decades, and we answer their most frequently asked questions. Other SHB services include the development of tissue microarrays (TMA). These enable end users to perform preliminary examinations of the expression and localisation of target molecules in diseased or aging donor hearts, all in a single section of the TMA. Finally, the processes involved in managing tissue requests from external users and logistics considerations for the shipment of human tissue are discussed in detail. PMID- 26998173 TI - Preparation and Antioxidant Activity of Purple Potato Wine. AB - Purple potatoes were used as raw material to study the purple potato wine production process and antioxidant activity. This paper analyzed different fermentation time, fermentation temperature, yeast inoculum, initial pH, the initial sugar content on alcohol and anthocyanin contents of purple potato wine by single factor experiments and response surface methodology(RSM). The results showed that the optimum fermentation conditions of purple potato wine were as follows: fermentation temperature was 26(o)C, yeast inoculum was 0.15%, fermentation time was 7 d, initial pH was 3.0 and initial sugar content was 11 %. Under these conditions the alcohol and anthocyanin contents of purple potato wine could reach 10.55%/Vol and 6.42 MUg/mL, respectively. The purple potato wine was purple, bright in colour, pleasant fragrance and pure taste. Prepared purple potato wine had the ability of reducing Fe(3+) and scavenging superoxide anion radicals, which meant that purple potato wine had certain antioxidant activity. PMID- 26998174 TI - Research on the Effect of Puerarin on Alleviating Sports Fatigue. AB - This paper focus on the effects of puerarin remit sports fatigue by observeing the effects of puerarinon blood components and exercise ability of mice in swimming trained. Comparing with the time of exhaustive swimming in the swim trained group, swim trained group with puerarin significantly increase (p<0.05). The puerarin may reduce the increase of hemoglobin, red blood cell and platelets caused by endurance exercise, reduce the blood viscosity, prolong the time of exhaustive swimming and improve exercise ability of mice in swim trained. Through the rat swimming experiment, we can further know the effects of puerarin on alleviating sports fatigue are obviously, which plays a role in the research field of the physiological effect of puerarin. PMID- 26998175 TI - The Research of the Effect of the Olive Juice on Anxiety and Depression Behavior. AB - In order to evaluate the effect of olive juice on the anxiety and depression behavior, the paper uses olive juice concentrate as experimental material, and uses mice as experimental subjects. Mice are randomly divided into negative, positive, high, medium and low-dose group, administered orally for 7 days. And observe the impact on the mice elevated plus maze test, the opening acts test and forced swim test. The experimental results show that under conditions of the sub acute administration, olive juice can induce anti-anxiety behavior of mice, but also has the potential to improve depression of mice. PMID- 26998176 TI - Protection of Lotus Seedpod Proanthocyanidins on Organs and Tissues under High intensity Excercise. AB - Lotus seedpod proanthocyanidins (LSPC) as a kind of polyphenols is widely used in medicines, cosmetics, health products. High-intensity exercise can cause damage to the body's organs and tissues. Different doses of LSPC is given to mice to check the function of protect effect to the body's organs and tissues under high intensity exercise. The hemoglobin (HB) content, red blood cell (RBC) number and white blood cell (WBC) number were tested for mice after exercise. The activity of superoxide dismutase (SOD) and the contents of glutathione (GSH) and malondialdehyde (MDA) in muscle and viscera were evaluated. The result showed that LSPC can effectively reduce inflammation reaction in the body of mice with high intensity exercise, alleviate oxidative stress-induced injury of tissues and organs, and execute protective function on skeletal muscle and cardiac muscle. And the LSPC could enhance myocardial anti-oxygen and enzymatic activity which suggests the protective effects of resveratrol against exercise-induced myocardial damage in mice. PMID- 26998177 TI - Biochemical Defenses Induced by Mycorrhizae Fungi Glomus Mosseae in Controlling Strawberry Fusarium Wilt. AB - The effect of VAM on reducing wilt caused by Fusarium oxysporum Schlecht. f.sp. fragariae Winks et Williams (FO) infection in strawberry and the possible mechanisms involved were investigated. Two key substance involved in disease defenses, lignin and hydroxyproline-rich glycoprotein were induced and formed in the cell wall of strawberry root, and the peak content of lignin and hydroxyproline-rich glycoprotein occurred on the 25(th) day (149.52mg/g) and on the 15(th) day (10.08 mg/g). The activity of protective enzymes SOD, POD and CAT inoculation with VAM significantly increased when compared with the control under both CK (natural growth) and inoculated with FO. The conductivity of VAM plus FO treatment was higher than the CK treatment, but significantly was lower than the FO treatment. PMID- 26998178 TI - The Research on the Effect of the Food with Different Glycaemic Index and Glycaemic Load on the Immunity of Endurance Athletes. AB - For studying the effect of eating the food containing carbohydrates with different glycaemic index and glycaemic load 2 hours before athletics on the exercise tolerance and immune function, select 10 men long-distance endurance athletes, use not completely random balance repeated testing methods, randomized complete the three endurance tests. And each test interval is not less than seven days. The results suggest that there is no apparent effect of eating the food containing carbohydrates with different glycaemic index and glycaemic load 2 hours before athletics on the exercise tolerance and immune function. Compared with the glycaemic index and glycaemic load of food, the carbohydrate content of the diet before athletics may be the more important factor affecting the immune response in endurance sports. PMID- 26998179 TI - Research on Effects and Compatibility Taking of Different Sports Supplements on the Biochemical Indicators and Body Functions of Elite Walking Athletes. AB - Scientific training, elimination of fatigue, and reasonable nutrition is the three important parts of successful training. Especially in the fatigue recovery and reasonable nutrition of track and field endurance project, which is more important than other project significance? This paper is to more scientific nutritional intervention on the walking athletes to improve athletic performance and provide experimental evidence 12 male and 12 female athletes were selected from the Chinese national walking team were given the nutrition intervention of a variety of sports supplements for 9 weeks. The serum testosterone (T), blood urea (BU), and serum creative phosphokinase (CK) and other indicators were tested in several weekends. The results showed that the different exercise taking supplements can increase the T levels of male and female walking athletes, and promote the body protein synthesis and the function of rapid recovery, reduce the levels of serum CK and BU abnormalities after the intensity training, and ensure the smooth completion of the training and a normal competitive level. The different exercise taking supplements can improve the biochemical indicators and improve the level of physical function. PMID- 26998180 TI - Research on the Influence of Anti-fatigue Effect and Movement Ability of Blueberry Polysaccharides on Aged Mice. AB - This topic introduces functions, extraction and purification of polysaccharides and focuses on the effect of blue polysaccharides (BPs) on sport capacity, anti fatigue effect and related physiological indexes in aged mice induced by D galactose was investigated. Water extract-alcohol precipitation method was used in the experiment to extract polysaccharides from blueberry, after preliminary purification, research on polysaccharide of its vitro antioxidant activity and bacteriostasis is taken, to provide a reference for the production and application of blueberry polysaccharides. Mice were randomly divided into normal control group, aged model group, low-dose BP group, middle-dose BP group, and high-dose BP group. After the administration of BPs for 20 consecutive days, the exhaustive swimming time and fatigue indexes were determined. The results showed that BPs could extend the exhaustive swimming time, decrease the content of BUN, BLA and MDA, and obviously increase the reservation of HG, MG, SOD and LDH. To conclude, BPs has good anti-fatigue effect. This study may provide theoretical evidence for the development of anti-fatigue drugs from BPs. PMID- 26998181 TI - The Research on the Impact of Green Beans Sports Drinks on Relieving Fatigue in Sports Training. AB - For researching the function of relieving fatigue of green beans sports drinks, this paper selected 60 mice as subjects. They were randomly divided into four groups (low dose group, middle dose group, high dose group and physiological saline group). Each time they were respectively feed 10g 20g/L, 40g/L, 80 g/L green beans sports drinks and 15ml/(kg.d) physiological saline. The experiment lasted for a month. We recorded weight of mice, swimming time and blood urea nitrogen indicators. The results show that green beans sports drinks can significantly prolong swimming time of mice (p <0.05). For serum urea the results show no effect. So green beans sports drinks have a certain function of relieving physical fatigue. PMID- 26998182 TI - The Research on the Impact of Maca Polypeptide on Sport Fatigue. AB - In order to study the effect of maca polypeptide on sport fatigue, this paper selected 40 male mice, and they were randomly divided into group A, B, C and D. group A, B and C were fed food with different concentrations of maca polypeptide, and group D was control group. After two weeks of feeding, measured physiological indexes of mice, including blood glucose, urea nitrogen and creatinine. At last gived the experimental results, as well as the analysis. Experimental results show that maca polypeptide can improve the ability of anti-fatigue mice, and in a certain concentration range, the higher the concentration, the better the resistance to fatigue. PMID- 26998183 TI - Effect of Malate-oligosaccharide Solution on Antioxidant Capacity of Endurance Athletes. AB - L-malate is an important intermediate on the process of metabolism; it plays an important role in generating mitochondria ATP both under aerobic and hypoxic condition. It is easy to be absorbed and come into mitochondrion through cell membrane and promote to produce energy in mitochondrion. The purpose of this investigation is to probe into the different influence malate ingestion on blood lactate and glucose kinetics during aerobic exercise athletes; at the same time, rats were used to study the effect of malate and oligosaccharide solution on the metabolism in muscle and liver. The supplement of malate-oligosaccharide solution may improve the level of antioxidants in vivo after exercise, and subsequently increase the total antioxidant capacity and decrease the level of lipid peroxidation. At the appropriate time sports drinks can add varying degrees of motion to extend time to fatigue enhance athletic ability, speed up the recovery process after exercise, reduce fatigue. PMID- 26998184 TI - The Reasearch on the Anti-Fatigue Effect of Whey Protein Powder in Basketball Training. AB - In order to observe the effects of whey protein powder on hematological indexes of players majoring in physical education in the basketball training, the authors divided the players randomly into a control group and a nutrition group. Athletes complete the 30 minutes quantitative exercise using cycle ergometer respectively before the trial and after one month trial. Then we exsanguinated immediately after exercise, extracted heparin and measured hemoglobin, red blood cell count, hematocrit and mean corpuscular volume and other hematological indices. The results showed that after taking whey protein powder, the HB, RBC, HCT of nutrition group was significantly higher that the control group. This suggests that in high-intensity training, taking whey protein powder can cause changes of HB, RBC and HCT in human body, meanwhile MCV essentially the same. So whey protein powder can improve exercise capacity, and has anti-fatigue effect. PMID- 26998185 TI - Optimization of Extraction Process for Polysaccharide in Salvia Miltiorrhiza Bunge Using Response Surface Methodology. AB - This study was aimed to optimize the extraction process for Salvia miltiorrhiza Bunge polysaccharide using response surface methodology The results showed that four operating parameters including microwave power, microwave time and the particle size had notable effects on the polysaccharide extraction of Salvia miltiorrhiza Bunge. The effects could be ranked in decreasing order of importance as follows:. Microwave power > microwave time > the comminution degree. The optimal extraction parameters were determined as 573.83W of Microwave power and 8.4min of microwave time and 67.51mesh of the comminution degree, resulting in the yield of Salvia miltiorrhiza Bunge polysaccharide of 101.161mg / g. The established regression model describing polysaccharide extraction from as a function of the three extraction parameters was highly significant (R 2 = 0.9953). The predicted and experimental results were found to be in good agreement. Thus, the model can be applicable for the prediction of polysaccharide extraction from Salvia miltiorrhiza Bunge. PMID- 26998186 TI - The role of etiopathogenetic aspects in prediction and prevention of discontinuous-hemorrhagic (Mallory-Weiss) syndrome. AB - The article contains an overview of the literature on Mallory-Weiss syndrome. It analyzes numerous etiological factors, provides new insights into the pathogenesis of the disease, gives a description of a previously unknown dependence of discontinuous-hemorrhagic syndrome on the topographic and structural features of the cardioesophageal area of the digestive tract, and gives scientific credence to methods of prediction, prevention, and treatment of the syndrome with complex involvement of granular sorbents. PMID- 26998187 TI - Hypercalcemia of Malignancy and Colorectal Cancer. AB - Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25 dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean +/- SD: 56.7 +/- 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean +/- SD: 15.6 +/- 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control. PMID- 26998188 TI - Densely-packed ZnTPPs Monolayer on the Rutile TiO2(110)-(1*1) Surface: Adsorption Behavior and Energy Level Alignment. AB - The adsorption of a densely packed Zinc(II) tetraphenylporphyrin monolayer on a rutile TiO2(110)-(1*1) surface has been studied using a combination of experimental and theoretical methods, aimed at analyzing the relation between adsorption behavior and barrier height formation. The adsorption configuration of ZnTPP was determined from scanning tunnel microscopy (STM) imaging, density functional theory (DFT) calculations and STM image simulation. The corresponding energy alignment was experimentally determined from X-ray and UV-photoemission spectroscopies and inverse photoemission spectroscopy. These results were found in good agreement with an appropriately corrected DFT model, pointing to the importance of local bonding and intermolecular interactions in the establishment of barrier heights. PMID- 26998189 TI - Adversity Across the Life Course of Incarcerated Parents: Gender Differences. AB - More than half of the 1.6 million adults in U.S. prions are parents. Despite growing knowledge regarding the life course adversities of corrections-involved populations, less is known regarding incarcerated parents per se and the implications of cumulative adversities both on their needs and those of their children. Using a gender-balanced (41% minority) sample of incarcerated parents (N=357) from a randomized controlled trial of an in-prison parent training program, this study examines differences between incarcerated mothers and fathers in their exposures to adversities across the life course. Mothers and fathers shared similar patterns of adversity exposure in their families of origin, but differed in their experiences of juvenile justice and child welfare systems involvement, as well as in their adult experiences of victimization and related adult social and mental health outcomes. Implications for gender-responsive parent support and prevention programs for their children of incarcerated mothers and fathers are discussed. PMID- 26998190 TI - Stratified Psychiatry via Convexity-Based Clustering with Applications Towards Moderator Analysis. AB - Understanding heterogeneity in phenotypical characteristics, symptoms manifestations and response to treatment of subjects with psychiatric illnesses is a continuing challenge in mental health research. A long-standing goal of medical studies is to identify groups of subjects characterized with a particular trait or quality and to distinguish them from other subjects in a clinically relevant way. This paper develops and illustrates a novel approach to this problem based on a method of optimal-partitioning (clustering) of functional data. The proposed method allows for the simultaneous clustering of different populations (e.g., symptoms of drug and placebo treated patients) in order to identify prototypical outcome profiles that are distinct from one or the other treatment and outcome profiles common to the different treatments. The clustering results are used to discover potential treatment effect modifiers (i.e., moderators), in particular, moderators of specific drug effects and placebo response. A depression clinical trial is used to illustrate the method. PMID- 26998191 TI - A clinical reading on "World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics". PMID- 26998192 TI - Antioxidant and Antiplasmodial Activities of Bergenin and 11-O-Galloylbergenin Isolated from Mallotus philippensis. AB - Two important biologically active compounds were isolated from Mallotus philippensis. The isolated compounds were characterized using spectroanalytical techniques and found to be bergenin (1) and 11-O-galloylbergenin (2). The in vitro antioxidant and antiplasmodial activities of the isolated compounds were determined. For the antioxidant potential, three standard analytical protocols, namely, DPPH radical scavenging activity (RSA), reducing power assay (RPA), and total antioxidant capacity (TAC) assay, were adopted. The results showed that compound 2 was found to be more potent antioxidant as compared to 1. Fascinatingly, compound 2 displayed better EC50 results as compared to alpha tocopherol while being comparable with ascorbic acid. The antiplasmodial assay data showed that both the compound exhibited good activity against chloroquine sensitive strain of Plasmodium falciparum (D10) and IC50 values were found to be less than 8 MUM. The in silico molecular docking analyses were also performed for the determination of binding affinity of the isolated compounds using P. falciparum proteins PfLDH and Pfg27. The results showed that compound 2 has high docking score and binding affinity to both protein receptors as compared to compound 1. The demonstrated biological potentials declared that compound 2 could be the better natural antioxidant and antiplasmodial candidate. PMID- 26998195 TI - Redox Status and Proteostasis in Ageing and Disease. PMID- 26998196 TI - Situation Selection and Modification for Emotion Regulation in Younger and Older Adults. AB - This research investigated age differences in use and effectiveness of situation selection and situation modification for emotion regulation. Socioemotional selectivity theory suggests stronger emotional well-being goals in older age; emotion regulation may support this goal. Younger and older adults assigned to an emotion regulation or "just view" condition first freely chose to engage with negative, neutral, or positive material (situation selection), then chose to view or skip negative and positive material (situation modification), rating affect after each experience. In both tasks, older adults in both goal conditions demonstrated pro-hedonic emotion regulation, spending less time with negative material compared to younger adults. Younger adults in the regulate condition also engaged in pro-hedonic situation selection, but not modification. Whereas situation selection was related to affect, modification of negative material was not. This research supports more frequent pro-hedonic motivation in older age, as well as age differences in use of early-stage emotion regulation. PMID- 26998194 TI - Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation. AB - Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO), abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site. PMID- 26998197 TI - Editor's Note. PMID- 26998198 TI - Thinking More Carefully About Respiratory Infections. PMID- 26998199 TI - Hepatitis B Infection: What The Primary Care Doctors Should Know. PMID- 26998193 TI - ROS and ROS-Mediated Cellular Signaling. AB - It has long been recognized that an increase of reactive oxygen species (ROS) can modify the cell-signaling proteins and have functional consequences, which successively mediate pathological processes such as atherosclerosis, diabetes, unchecked growth, neurodegeneration, inflammation, and aging. While numerous articles have demonstrated the impacts of ROS on various signaling pathways and clarify the mechanism of action of cell-signaling proteins, their influence on the level of intracellular ROS, and their complex interactions among multiple ROS associated signaling pathways, the systemic summary is necessary. In this review paper, we particularly focus on the pattern of the generation and homeostasis of intracellular ROS, the mechanisms and targets of ROS impacting on cell-signaling proteins (NF-kappaB, MAPKs, Keap1-Nrf2-ARE, and PI3K-Akt), ion channels and transporters (Ca(2+) and mPTP), and modifying protein kinase and Ubiquitination/Proteasome System. PMID- 26998200 TI - Insomnia: Case Studies In Family Practice. PMID- 26998202 TI - Clinical features of acute thrombocytopaenia among patients attending primary care clinics. PMID- 26998201 TI - Clinical Features Of Acute Febrile Thrombocytopaenia Among Patients Attending Primary Care Clinics. AB - INTRODUCTION: Identifying clinical features that differentiate acute febrile thrombocytopaenia from acute febrile illness without thrombocytopaenia can help primary care physician to decide whether to order a full blood count (FBC). This is important because thrombocytopaenia in viral fever may signify more serious underlying aetiology like dengue infection. OBJECTIVE: The aim of this study was to compare the clinical features of acute febrile patients with thrombocytopaenia and acute febrile patients without thrombocytopaenia. METHODOLOGY: This was a clinic-based cross-sectional study from May to November 2003. Consecutive patients presenting with undifferentiated fever of less than two weeks were selected from the Primary Care Centre of Hospital Universiti Kebangsaan Malaysia and Batu 9 Cheras Health Clinic. Clinical features of these patients were recorded and FBC examination was done for all patients. Thrombocytopaenia was defined as platelet count <150X10(9)/L. The odds ratio of thrombocytopaenia for each presenting symptoms was calculated. RESULT: Seventy-three patients participated in this study. Among them, 45.2% had thrombocytopaenia. Myalgia and headache were common among all patients. However, nausea and vomiting occurred significantly more often among patients with thrombocytopaenia than in patients with normal platelet count (OR 2.2, 95% CI 1.1-4.5). CONCLUSION: Acute non specific febrile patients presenting with symptoms of nausea and vomiting may have higher risk of thrombocytopaenia and should be seriously considered for FBC. KEY WORDS: viral infection, dengue, clinical features, thrombocytopaenia. PMID- 26998203 TI - Prevalence Of Diabetic Retinopathy In A Primary Care Setting Using Digital Retinal Imaging Technology. AB - The objective of this study was to determine the prevalence of diabetic retinopathy in a primary care setting using digital retinal imaging technology and to quantify the degree of diabetic retinopathy using internationally accepted severity scales. Two hundred patients with type 2 diabetes were evaluated clinically followed by fundus photography. The prevalence of retinopathy and maculopathy was 47.4% and 59.2% respectively (both retinopathy and maculopathy 34.7%). The high prevalence of retinal abnormality in this study is a cause for concern as most patients had diabetes for only 5 years or less. PMID- 26998204 TI - Prevalence of diabetic retinopathy in a primary care setting using digital retinal imaging technology. PMID- 26998205 TI - An Elderly Woman With Intermittent Claudication. AB - This case report illustrates the misdiagnosis of intermittent claudication in an elderly with multiple cardiac risk factors. Careful clinical evaluation and imaging shifts the diagnosis from peripheral vascular disease to spinal stenosis. The decision whether to offer conservative therapy or proceed to spinal surgery requires an accurate assessment of the severity of the symptoms without ignoring the important role of patient preferences. PMID- 26998206 TI - A Case Of Tubal Ectopic Pregnancy. AB - A healthy 27 year old Para 3 presenting with abnormal menstruation without a period of amenorrhoea was diagnosed to have left tubal ectopic pregnancy after vaginal examination and abdominal ultrasonography. The case illustrates the need for careful history taking and the need for considering ectopic pregnancy in women in the reproductive age group, who have abnormal menstruation even if they are on contraception. PMID- 26998207 TI - Is There A Role For Aspirin In Primary Prevention Of Ischemic Heart Disease In Hypertensive Patients? PMID- 26998208 TI - What Study Design Should I Choose? PMID- 26998209 TI - Designing A Questionnaire. PMID- 26998210 TI - Funding For Research: How To Navigate Towards It. PMID- 26998211 TI - Retinal Images. PMID- 26998212 TI - A Man With Dyslipidemia: To Treat Or Not To Treat? PMID- 26998213 TI - Beauty Or Health? A Personal View. AB - This paper deals with the question of beauty and health in women. It discusses changing definitions of beauty as a result of influences from the entertainment, beauty and health product industries. Advertisements are seen to be major players in defining beauty through promotion of cosmetic, skin, hair and slimming products. Concerns relating to beauty become inculcated in girls through the process of socialisation as they mature into womanhood. The media plays a significant role in portraying the meaning of beauty through its representation of women. These influences largely influence and alter women's perceptions of their body image and in trying to meet the goals of beauty as represented by the media. This may result in dissatisfaction with their body image. Advertisements can encourage women to indulge in smoking as a fashionable trend or opt for plastic surgery in attempts to acquire beauty. This paper concludes with implications of the issues relating to changing perceptions of beauty and suggests recommendations. PMID- 26998214 TI - Rapid DNA analysis for automated processing and interpretation of low DNA content samples. AB - BACKGROUND: Short tandem repeat (STR) analysis of casework samples with low DNA content include those resulting from the transfer of epithelial cells from the skin to an object (e.g., cells on a water bottle, or brim of a cap), blood spatter stains, and small bone and tissue fragments. Low DNA content (LDC) samples are important in a wide range of settings, including disaster response teams to assist in victim identification and family reunification, military operations to identify friend or foe, criminal forensics to identify suspects and exonerate the innocent, and medical examiner and coroner offices to identify missing persons. Processing LDC samples requires experienced laboratory personnel, isolated workstations, and sophisticated equipment, requires transport time, and involves complex procedures. We present a rapid DNA analysis system designed specifically to generate STR profiles from LDC samples in field-forward settings by non-technical operators. By performing STR in the field, close to the site of collection, rapid DNA analysis has the potential to increase throughput and to provide actionable information in real time. RESULTS: A Low DNA Content BioChipSet (LDC BCS) was developed and manufactured by injection molding. It was designed to function in the fully integrated Accelerated Nuclear DNA Equipment (ANDE) instrument previously designed for analysis of buccal swab and other high DNA content samples (Investigative Genet. 4(1):1-15, 2013). The LDC BCS performs efficient DNA purification followed by microfluidic ultrafiltration of the purified DNA, maximizing the quantity of DNA available for subsequent amplification and electrophoretic separation and detection of amplified fragments. The system demonstrates accuracy, precision, resolution, signal strength, and peak height ratios appropriate for casework analysis. CONCLUSIONS: The LDC rapid DNA analysis system is effective for the generation of STR profiles from a wide range of sample types. The technology broadens the range of sample types that can be processed and minimizes the time between sample collection, sample processing and analysis, and generation of actionable intelligence. The fully integrated Expert System is capable of interpreting a wide range or sample types and input DNA quantities, allowing samples to be processed and interpreted without a technical operator. PMID- 26998215 TI - Chemoenzymatic exchange of phosphopantetheine on protein and peptide. AB - Evaluation of new acyl carrier protein hydrolase (AcpH, EC 3.1.4.14) homologs from proteobacteria and cyanobacteria reveals significant variation in substrate selectivity and kinetic parameters for phosphopantetheine hydrolysis from carrier proteins. Evaluation with carrier proteins from both primary and secondary metabolic pathways reveals an overall preference for acyl carrier protein (ACP) substrates from type II fatty acid synthases, as well as variable activity for polyketide synthase ACPs and peptidyl carrier proteins (PCP) from non-ribosomal peptide synthases. We also demonstrate the kinetic parameters of these homologs for AcpP and the 11-mer peptide substrate YbbR. These findings enable the fully reversible labeling of all three classes of natural product synthase carrier proteins as well as full and minimal fusion protein constructs. PMID- 26998216 TI - Sex-specific genetic effects associated with pigmentation, sensitivity to sunlight, and melanoma in a population of Spanish origin. AB - BACKGROUND: Human pigmentation is a polygenic quantitative trait with high heritability. In addition to genetic factors, it has been shown that pigmentation can be modulated by oestrogens and androgens via up- or down-regulation of melanin synthesis. Our aim was to identify possible sex differences in pigmentation phenotype as well as in melanoma association in a melanoma case control population of Spanish origin. METHODS: Five hundred and ninety-nine females (316 melanoma cases and 283 controls) and 458 males (234 melanoma cases and 224 controls) were analysed. We genotyped 363 polymorphisms (single nucleotide polymorphisms (SNPs)) from 65 pigmentation gene regions. RESULTS: When samples were stratified by sex, we observed more SNPs associated with dark pigmentation and good sun tolerance in females than in males (107 versus 75; P = 2.32 * 10(-6)), who were instead associated with light pigmentation and poor sun tolerance. Furthermore, six SNPs in TYR, SILV/CDK2, GPR143, and F2RL1 showed strong differences in melanoma risk by sex (P < 0.01). CONCLUSIONS: We demonstrate that these genetic variants are important for pigmentation as well as for melanoma risk, and also provide suggestive evidence for potential differences in genetic effects by sex. PMID- 26998217 TI - Single-cell analysis reveals differential regulation of the alveolar macrophage actin cytoskeleton by surfactant proteins A1 and A2: implications of sex and aging. AB - BACKGROUND: Surfactant protein A (SP-A) contributes to lung immunity by regulating inflammation and responses to microorganisms invading the lung. The huge genetic variability of SP-A in humans implies that this protein is highly important in tightly regulating the lung immune response. Proteomic studies have demonstrated that there are differential responses of the macrophages to SP-A1 and SP-A2 and that there are sex differences implicated in these responses. METHODS: Purified SP-A variants were used for administration to alveolar macrophages from SP-A knockout (KO) mice for in vitro studies, and alveolar macrophages from humanized SP-A transgenic mice were isolated for ex vivo studies. The actin cytoskeleton was examined by fluorescence and confocal microscopy, and the macrophages were categorized according to the distribution of polymerized actin. RESULTS: In accordance with previous data, we report that there are sex differences in the response of alveolar macrophages to SP-A1 and SP A2. The cell size and F-actin content of the alveolar macrophages are sex- and age-dependent. Importantly, there are different subpopulations of cells with differential distribution of polymerized actin. In vitro, SP-A2 destabilizes actin in female, but not male, mice, and the same tendency is observed by SP-A1 in cells from male mice. Similarly, there are differences in the distribution of AM subpopulations isolated from SP-A transgenic mice depending on sex and age. CONCLUSIONS: There are marked sex- and age-related differences in the alveolar macrophage phenotype as illustrated by F-actin staining between SP-A1 and SP-A2. Importantly, the phenotypic switch caused by the different SP-A variants is subtle, and pertains to the frequency of the observed subpopulations, demonstrating the need for single-cell analysis approaches. The differential responses of alveolar macrophages to SP-A1 and SP-A2 highlight the importance of genotype in immune regulation and the susceptibility to lung disease and the need for development of individualized treatment options. PMID- 26998219 TI - A season of snakebite envenomation: presentation patterns, timing of care, anti venom use, and case fatality rates from a hospital of southcentral Nepal. AB - Snakebite envenomation affects thousands of people annually in Nepal. Published hospital-based studies of snakebite treatment in Nepal are scarce. Here we present the results of the first prospective, cross-sectional study of hospitalized envenomed snakebite cases in southcentral Nepal, a region characterized by poor pre-hospital care of snakebites, limited supply and excessive use of antivenom, and a high case/fatality ratio. We seek to identify clinical management problems and suggest potential interventions to improve treatment of snakebites. Out of the 342 patients presented with snakebites to an urban emergency department in the Terai region of Nepal between April and September of 2007, 39 patients were enrolled based on development of ptosis or swelling of bitten body parts. We collected patient demographic information and documented circumstances of snakebite, prehospital care, hospital care, and development of complications. Among 39 envenomated patients admitted to Bharatpur Hospital enrolled in the study 34 (92%) exhibited features of clinically significant neurotoxicity and were treated with antivenom. Antivenom use ranged from 4 to 98 vials of Polyspecific Indian Antivenom per patient. Each of victims (n=34) received antivenom an average of 4.3 (median) +/-0.73 (standard error of mean) hours after receiving the snakebite. The overall case fatality rate was 21%. Neurotoxicity developed up to 25.8hr after suspected elapid snakebites. This was not observed for viperid snake bites. No enrolled patients received any of the currently recommended first aid for snake bite. The prevalence of nocturnal elapid snake bites, the practice of inappropriate first aid measures and highly variable administration of antivenom were identified as major challenges to appropriate care in this study. To address these issues we suggest development of a comprehensive checklist for identification of snake species, management of envenomation, and an educational program which teaches proper care at all stages of snakebite treatment. PMID- 26998218 TI - Venom gland components of the ectoparasitoid wasp, Anisopteromalus calandrae. AB - The wasp Anisopteromalus calandrae is a small ectoparasitoid that attacks stored product pest beetle larvae that develop inside grain kernels, and is thus a potential insect control tool. The components of A. calandrae venom have not been studied, but venom from other organisms contains proteins with potential applications, such as pest management tools and treatments for human diseases. We dissected female A. calandrae and collected venom and associated glands. Using high throughput sequencing, a venom gland transcriptome was assembled that contained 45,432 contigs, 25,726 of which had BLASTx hits. The majority of hits were to Nasonia vitripennis, an ectoparasitoid from the same taxonomic family, as well as other bees, wasps, and ants. Gene ontology grouped sequences into eleven molecular functions, among which binding and catalytic activity had the most representatives. In this study, we highlighted the most abundant sequences, including those that are likely the functional components of the venom. Specifically, we focused on genes encoding proteins potentially involved in host developmental arrest, disrupting the host immune system, host paralysis, and transcripts that support these functions. Our report is the first to characterize components of the A. calandrae venom gland that may be useful as control tools for insect pests and other applications. PMID- 26998220 TI - Intermediate hepatocellular carcinoma: the role of transarterial therapy. AB - According to Barcelona Clinic Liver Cancer, the recommended first-line treatment for patients with intermediate stage of hepatocellular carcinoma (HCC) is transarterial chemoembolization. Patients with intermediate stage of HCC represent 20% with a 2-year survival of approximately 50%. Nowadays, transarterial therapies have proved precious in the treatment of hepatic malignancies. During the last years, there were important developments in practiced transarterial therapies and their efficacy is still controversial. The purpose of this review is to discuss in further details these transarterial therapies that have been used to treat cases of HCC. PMID- 26998223 TI - Highlights of the 1st Student Symposium of the ISCB RSG UK. AB - This short report summarises the scientific content and activities of a student led event, the 1st student symposium by the UK Regional Student Group of the International Society for Computational Biology. The event took place on the 8th of October 2014. PMID- 26998222 TI - Primary Kaposi's sarcoma of the nasal cavity: a case report and review of the literature. AB - BACKGROUND: Kaposi sarcoma is a neoplastic vascular disorder. It usually present on the skin of the upper and lower extremities, rarely in the mucosa of the head and neck. The most common sites reported are within the oral cavity, particularly on the palate. Other mucosal sites are rare. We present an unusual case where the primary manifestation of the Kaposi's sarcoma was in the nasal mucosa. CASE PRESENTATION: A 56-year-old female of Mediterranean descent presented with a 1 year history of swelling on the left side of her nose, nasal obstruction and occasional minor epistaxes. Physical examination showed a firm and bulging polypoid mass which filled the left nasal cavity without cutaneous lesions. Computed tomography (CT) demonstrated a tumor, measuring 77 mm in diameter, occupying the left nasal cavity causing erosion of nasal septum and extending posteriorly to the left choana and nasopharynx. There was bilateral cervical lymphadenopathy. Patient treated with chemotherapy alone. She was in a complete response after the first cycle. The patient received no further treatment. She needs a regular medical checkups that include a review of a patient's medical history and a complete physical exam. She is in excellent local control over 12 months. CONCLUSIONS: A review of the literature revealed that only seven cases of primary Kaposi sarcoma of the nasal cavity have previously been published and only two of them presented in a patient not associated with the acquired immunodeficiency syndrome. Here, we report the third case where the primary manifestation of the Kaposi sarcoma was in the nasal cavity in a patient with an adequate immune system. PMID- 26998224 TI - The Bioconductor channel in F1000Research. AB - Bioconductor ( bioconductor.org) is a rich source of software and know-how for the integrative analysis of genomic data. The Bioconductor channel in F1000Research provides a forum for task-oriented workflows that each cover a solution to a current, important problem in genome-scale data analysis from end to end, invoking resources from several packages by different authors, often combining multiple 'omics data types, and demonstrating integrative analysis and modelling techniques. PMID- 26998221 TI - Mechanisms of doxorubicin resistance in hepatocellular carcinoma. AB - Hepatocellular carcinoma, one of the most common solid tumors worldwide, is poorly responsive to available chemotherapeutic approaches. While systemic chemotherapy is of limited benefit, intra-arterial delivery of doxorubicin to the tumor frequently produces tumor shrinkage. Its utility is limited, in part, by the frequent emergence of doxorubicin resistance. The mechanisms of this resistance include increased expression of multidrug resistance efflux pumps, alterations of the drug target, topoisomerase, and modulation of programmed cell death pathways. Many of these effects result from changes in miRNA expression and are particularly prominent in tumor cells with a stem cell phenotype. This review will summarize the current knowledge on the mechanisms of doxorubicin resistance of hepatocellular carcinoma and the potential for approaches toward therapeutic chemosensitization. PMID- 26998225 TI - Variable effects of nicotine and anabasine on parasitized bumble bees. AB - Secondary metabolites in floral nectar have been shown to reduce parasite load in two common bumble bee species. Previous studies on the effects of nectar secondary metabolites on parasitized bees have focused on single compounds in isolation; however, in nature, bees are simultaneously exposed to multiple compounds. We tested for synergistic effects of two alkaloids found in the nectar of Nicotiana spp. plants, nicotine and anabasine, on parasite load and mortality in bumble bees ( Bombus impatiens) infected with the intestinal parasite Crithidia bombi. Adult worker bees inoculated with C. bombi were fed nicotine and anabasine diet treatments in a factorial design, resulting in four nectar treatment combinations: 2 ppm nicotine, 5 ppm anabasine, 2ppm nicotine and 5 ppm anabasine together, or a control alkaloid-free solution. We conducted the experiment twice: first, with bees incubated under variable environmental conditions ('Variable'; temperatures varied from 10-35 degrees C); and second, under carefully controlled environmental conditions ('Controlled'; 27 degrees C incubator, constant darkness). In 'Variable', each alkaloid alone significantly decreased parasite loads, but this effect was not realized with the alkaloids in combination, suggesting an antagonistic interaction. Nicotine but not anabasine significantly increased mortality, and the two compounds had no interactive effects on mortality. In 'Controlled', nicotine significantly increased parasite loads, the opposite of its effect in 'Variable'. While not significant, the relationship between anabasine and parasite loads was also positive. Interactive effects between the two alkaloids on parasite load were non-significant, but the pattern of antagonistic interaction was similar to that in the variable experiment. Neither alkaloid, nor their interaction, significantly affected mortality under controlled conditions. Our results do not indicate synergy between Nicotiana nectar alkaloids; however, they do suggest a complex interaction between secondary metabolites, parasites, and environmental variables, in which secondary metabolites can be either toxic or medicinal depending on context. PMID- 26973784 TI - Effect of the synthesis of rice non-symbiotic hemoglobins 1 and 2 in the recombinant Escherichia coli TB1 growth. AB - Non-symbiotic hemoglobins (nsHbs) are widely distributed in land plants, including rice. These proteins are classified into type 1 (nsHbs-1) and type 2. The O 2-affinity of nsHbs-1 is very high mostly because of an extremely low O 2 dissociation rate constant resulting in that nsHbs-1 apparently do not release O 2 after oxygenation. Thus, it is possible that the in vivo function of nsHbs-1 is other than O 2-transport. Based on the properties of multiple Hbs it was proposed that nsHbs-1 could play diverse roles in rice organs, however the in vivo activity of rice nsHbs-1 has been poorly analyzed. An in vivo analysis for rice nsHbs-1 is essential to elucidate the biological function(s) of these proteins. Rice Hb1 and Hb2 are nsHbs-1 that have been generated in recombinant Es cherichia coli TB1. The rice Hb1 and Hb2 amino acid sequence, tertiary structure and rate and equilibrium constants for the reaction of O 2 are highly similar. Thus, it is possible that rice Hb1 and Hb2 function similarly in vivo. As an initial approach to test this hypothesis we analyzed the effect of the synthesis of rice Hb1 and Hb2 in the recombinant E. coli TB1 growth. Effect of the synthesis of the O 2 carrying soybean leghemoglobin a, cowpea leghemoglobin II and Vitreoscilla Hb in the recombinant E. coli TB1 growth was also analyzed as an O 2-carrier control. Our results showed that synthesis of rice Hb1, rice Hb2, soybean Lb a, cowpea LbII and Vitreoscilla Hb inhibits the recombinant E. coli TB1 growth and that growth inhibition was stronger when recombinant E. coli TB1 synthesized rice Hb2 than when synthesized rice Hb1. These results suggested that rice Hb1 and Hb2 could function differently in vivo. PMID- 26998227 TI - A disruptive sequencer meets disruptive publishing. AB - Nanopore sequencing was recently made available to users in the form of the Oxford Nanopore MinION. Released to users through an early access programme, the MinION is made unique by its tiny form factor and ability to generate very long sequences from single DNA molecules. The platform is undergoing rapid evolution with three distinct nanopore types and five updates to library preparation chemistry in the last 18 months. To keep pace with the rapid evolution of this sequencing platform, and to provide a space where new analysis methods can be openly discussed, we present a new F1000Research channel devoted to updates to and analysis of nanopore sequence data. PMID- 26998228 TI - A new Critical Care channel in F1000Research. AB - A new channel for Critical Care offers clinicians and medical researchers a platform for publishing new research without the barriers and delays they often encounter in traditional journals. The channel welcomes research and debate across the broad field of acute care and emergency medicine, including confirmatory and negative/null studies supported by new data. PMID- 26998229 TI - FlyOde - a platform for community curation and interactive visualization of dynamic gene regulatory networks in Drosophila eye development. AB - MOTIVATION: Understanding the regulatory mechanisms governing eye development of the model organism Drosophila melanogaster (D. m.) requires structured knowledge of the involved genes and proteins, their interactions, and dynamic expression patterns. Especially the latter information is however to a large extent scattered throughout the literature. RESULTS: FlyOde is an online platform for the systematic assembly of data on D. m. eye development. It consists of data on eye development obtained from the literature, and a web interface for users to interactively display these data as a gene regulatory network. Our manual curation process provides high standard structured data, following a specifically designed ontology. Visualization of gene interactions provides an overview of network topology, and filtering according to user-defined expression patterns makes it a versatile tool for daily tasks, as demonstrated by usage examples. Users are encouraged to submit additional data via a simple online form. PMID- 26998231 TI - Highlights of the first ISCB Student Council Symposium in Africa 2015. AB - This is a summary of the activities and scientific content of the first International Society for Computational Biology Student Council symposium in Africa. This meeting organized by the students for the students took place 8th of March 2015 in Dar Es Salaam, Tanzania. PMID- 26998230 TI - Deep sequencing revealed molecular signature of horizontal gene transfer of plant like transcripts in the mosquito Anopheles culicifacies: an evolutionary puzzle. AB - In prokaryotes, horizontal gene transfer (HGT) has been regarded as an important evolutionary drive to acquire and retain beneficial genes for their survival in diverse ecologies. However, in eukaryotes, the functional role of HGTs remains questionable, although current genomic tools are providing increased evidence of acquisition of novel traits within non-mating metazoan species. Here, we provide another transcriptomic evidence for the acquisition of massive plant genes in the mosquito, Anopheles culicifacies. Our multiple experimental validations including genomic PCR, RT-PCR, real-time PCR, immuno-blotting and immuno-florescence microscopy, confirmed that plant like transcripts (PLTs) are of mosquito origin and may encode functional proteins. A comprehensive molecular analysis of the PLTs and ongoing metagenomic analysis of salivary microbiome provide initial clues that mosquitoes may have survival benefits through the acquisition of nuclear as well as chloroplast encoded plant genes. Our findings of PLTs further support the similar questionable observation of HGTs in other higher organisms, which is still a controversial and debatable issue in the community of evolutionists. We believe future understanding of the underlying mechanism of the feeding associated molecular responses may shed new insights in the functional role of PLTs in the mosquito. PMID- 26998233 TI - Profiling and tandem mass spectrometry analysis of aminoacylated phospholipids in Bacillus subtilis . AB - Cationic modulation of the dominantly negative electrostatic structure of phospholipids plays an important role in bacterial response to changes in the environment. In addition to zwitterionic phosphatidylethanolamine, Gram-positive bacteria are also abundant in positively charged lysyl-phosphatidylglycerol. Increased amounts of both types of lipids render Gram-positive bacterial cells more resistant to cationic antibiotic peptides such as defensins. Lysyl and alanyl-phosphatidylglycerol as well as alanyl-cardiolipin have also been studied by mass spectroscopy. Phospholipids modified by other amino acids have been discovered by chemical analysis of the lipid lysate but have yet to be studied by mass spectroscopy. We exploited the high sensitivity of modern mass spectroscopy in searching for substructures in complex mixtures to establish a sensitive and thorough screen for aminoacylated phospholipids. The search for deprotonated aminoacyl anions in lipid extracted from Bacillus subtilis strain 168 yielded strong evidence as well as relative abundance of aminoacyl-phosphatidylglycerols, which serves as a crude measure of the specificity of aminoacyl phosphatidylglycerol synthase MprF. No aminoacyl-cardiolipin was found. More importantly, the second most abundant species in this category is D-alanyl phosphatidylglycerol, suggesting a possible role in the D-alanylation pathway of wall- and lipo-teichoic acids. PMID- 26989472 TI - Recent advances in the elucidation of enzymatic function in natural product biosynthesis. AB - With the successful production of artemisinic acid in yeast, the promising potential of synthetic biology for natural product biosynthesis is now being realized. The recent total biosynthesis of opioids in microbes is considered to be another landmark in this field. The importance and significance of enzymes in natural product biosynthetic pathways have been re-emphasized by these advancements. Therefore, the characterization and elucidation of enzymatic function in natural product biosynthesis are undoubtedly fundamental for the development of new drugs and the heterologous biosynthesis of active natural products. Here, discoveries regarding enzymatic function in natural product biosynthesis over the past year are briefly reviewed. PMID- 26998235 TI - Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases? AB - A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation of protein aggregates such as alpha-synuclein in Parkinson's disease, TDP-43 in ALS, and tau in Alzheimer's disease. Enhancing intracellular clearance of aggregation-prone proteins is a plausible strategy for slowing progression of neurodegenerative diseases and there is great interest in identifying molecular targets that control protein turnover. One of the main routes for protein degradation is through the proteasome, a multisubunit protease that degrades proteins that have been tagged with a polyubiquitin chain by ubiquitin activating and conjugating enzymes. Published data from cellular models indicate that Ubiquitin-specific protease 14 (USP14), a deubiquitinating enzyme (DUB), slows the degradation of tau and TDP-43 by the proteasome and that an inhibitor of USP14 increases the degradation of these substrates. We conducted similar experiments designed to evaluate tau, TDP-43, or alpha-synuclein levels in cells after overexpressing USP14 or knocking down endogenous expression by siRNA. PMID- 26998234 TI - Publishing confirming and non-confirming data. AB - This editorial introduces the Preclinical Reproducibility and Robustness channel on F1000Research, which has been created to encourage and facilitate open and transparent publication and discussion of confirmatory and non-confirmatory studies in biomedical research. PMID- 26998236 TI - Sequence and intramolecular distance scoring analyses of microbial rhodopsins. AB - Recent accumulation of sequence and structural data, in conjunction with systematical classification into a set of families, has significantly advanced our understanding of diverse and specific protein functions. Analysis and interpretation of protein family data requires comprehensive sequence and structural alignments. Here, we present a simple scheme for analyzing a set of experimental structures of a given protein or family of proteins, using microbial rhodopsins as an example. For a data set comprised of around a dozen highly similar structures to each other (overall pairwise root-mean-squared deviation < 2.3 A), intramolecular distance scoring analysis yielded valuable information with respect to structural properties, such as differences in the relative variability of transmembrane helices. Furthermore, a comparison with recent results for G protein-coupled receptors demonstrates how the results of the present analysis can be interpreted and effectively utilized for structural characterization of diverse protein families in general. PMID- 26998238 TI - Should there be greater use of preprint servers for publishing reports of biomedical science? AB - Vitek Tracz and Rebecca Lawrence declare the current journal publishing system to be broken beyond repair. They propose that it should be replaced by immediate publication followed by transparent peer review as the starting place for more open and efficient reporting of science. While supporting this general objective, we suggest that research is needed both to understand why biomedical scientists have been slow to take up preprint options, as well as to assess the relative merits of this and other alternatives to journal publishing. PMID- 26998237 TI - Phytoglobin: a novel nomenclature for plant globins accepted by the globin community at the 2014 XVIII conference on Oxygen-Binding and Sensing Proteins. AB - Hemoglobin (Hb) is a heme-containing protein found in the red blood cells of vertebrates. For many years, the only known Hb-like molecule in plants was leghemoglobin (Lb). The discovery that other Hb-like proteins existed in plants led to the term "nonsymbiotic Hbs (nsHbs)" to differentiate them from the Lbs. While this terminology was adequate in the early stages of research on the protein, the complexity of the research in this area necessitates a change in the definition of these proteins to delineate them from red blood cell Hb. At the 2014 XVIII Conference on Oxygen-Binding and Sensing Proteins, the group devoted to the study of heme-containing proteins, this issue was discussed and a consensus was reached on a proposed name change. We propose Phytoglobin (Phytogb) as a logical, descriptive name to describe a heme-containing (Hb-like) protein found in plants. It will be readily recognized by the research community without a prolonged explanation of the origin of the term. The classification system that has been established can essentially remain unchanged substituting Phytogb in place of nsHb. Here, we present a guide to the new nomenclature, with reference to the existing terminology and a phylogenetic scheme, placing the known Phytogbs in the new nomenclature. PMID- 26998239 TI - Communities of practice in life sciences and the need for brokering. AB - Etienne Wenger's work on communities of practice is influential in teaching and learning in higher education. A core work of many postgraduate certificate in teaching and learning (PGCert) courses for new lecturers, it is studied, in the main, as a means to understand how to support and encourage students to achieve more effective learning. Communities of practice can also be applied to academics. In the context of the Research Excellence Framework (REF) and its predecessors, the gulf between research-focused and teaching-Focused academics in life sciences has widened, so that in many institutions, these two groups have evolved into two distinct communities of practice; one whose priority is disciplinary research, the other's learning and teaching. However, in 2015, the UK government announced that a Teaching Excellence Framework (TEF) would be introduced into higher education in England, as early as 2017. While the exact details of TEF remain unclear, it is certain that "excellence" and "student satisfaction" will be high on the agenda. It is vital, therefore, that the two communities of practice, research-focused and teaching-focused, find ways to come together in order to ensure high quality teaching and learning. Wenger proposes that this can be done through the process of "brokering", which allows expertise from both communities of practice to cross from one to the other, strengthening both. This should be encouraged at departmental and institutional level, but another vital origin of brokering can be forged at a(n) (inter)national level at meetings such as the SEB Annual Conference, where teaching-focused academics have the opportunity to mix with research-active colleagues. While this paper is informed by recent and current events in the UK Higher Education sector, it is of interest to academics who work in an environment where research and teaching have become separate to any extent. PMID- 26998240 TI - siRNA knockdown validation 101: Incorporating negative controls in antibody research. AB - More antibody validation protocols would identify non-specific reagents - a major source of irreproducible research - with the inclusion of negative controls. This article presents an overview of one such method: siRNA knockdown. The authors outline a general protocol, the knockdown mechanism, and tips for evaluating knockdown experiments. PMID- 26998241 TI - ISCB's initial reaction to New England Journal of Medicine editorial on data sharing. AB - This message is a response from the ISCB in light of the recent the New England Journal of Medicine (NEJM) editorial around data sharing. PMID- 26998242 TI - The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system? AB - Barrier mechanisms in the brain are important for its normal functioning and development. Stability of the brain's internal environment, particularly with respect to its ionic composition, is a prerequisite for the fundamental basis of its function, namely transmission of nerve impulses. In addition, the appropriate and controlled supply of a wide range of nutrients such as glucose, amino acids, monocarboxylates, and vitamins is also essential for normal development and function. These are all cellular functions across the interfaces that separate the brain from the rest of the internal environment of the body. An essential morphological component of all but one of the barriers is the presence of specialized intercellular tight junctions between the cells comprising the interface: endothelial cells in the blood-brain barrier itself, cells of the arachnoid membrane, choroid plexus epithelial cells, and tanycytes (specialized glial cells) in the circumventricular organs. In the ependyma lining the cerebral ventricles in the adult brain, the cells are joined by gap junctions, which are not restrictive for intercellular movement of molecules. But in the developing brain, the forerunners of these cells form the neuroepithelium, which restricts exchange of all but the smallest molecules between cerebrospinal fluid and brain interstitial fluid because of the presence of strap junctions between the cells. The intercellular junctions in all these interfaces are the physical basis for their barrier properties. In the blood-brain barrier proper, this is combined with a paucity of vesicular transport that is a characteristic of other vascular beds. Without such a diffusional restrain, the cellular transport mechanisms in the barrier interfaces would be ineffective. Superimposed on these physical structures are physiological mechanisms as the cells of the interfaces contain various metabolic transporters and efflux pumps, often ATP-binding cassette (ABC) transporters, that provide an important component of the barrier functions by either preventing entry of or expelling numerous molecules including toxins, drugs, and other xenobiotics. In this review, we summarize these influx and efflux mechanisms in normal developing and adult brain, as well as indicating their likely involvement in a wide range of neuropathologies. There have been extensive attempts to overcome the barrier mechanisms that prevent the entry of many drugs of therapeutic potential into the brain. We outline those that have been tried and discuss why they may so far have been largely unsuccessful. Currently, a promising approach appears to be focal, reversible disruption of the blood-brain barrier using focused ultrasound, but more work is required to evaluate the method before it can be tried in patients. Overall, our view is that much more fundamental knowledge of barrier mechanisms and development of new experimental methods will be required before drug targeting to the brain is likely to be a successful endeavor. In addition, such studies, if applied to brain pathologies such as stroke, trauma, or multiple sclerosis, will aid in defining the contribution of brain barrier pathology to these conditions, either causative or secondary. PMID- 26998243 TI - Advances in the prevention, management, and treatment of community-acquired pneumonia. AB - Community-acquired pneumonia (CAP) is the infectious disease with the highest number of deaths worldwide. Nevertheless, its importance is often underestimated. Large cohorts of patients with CAP have been established worldwide and improved our knowledge about CAP by far. Therefore, current guidelines are much more evidence-based than ever before. This article discusses recent major studies and concepts on CAP such as the role of biomarkers, appropriate risk stratification to identify patients in need of hospitalisation or intensive care, appropriate empiric antibiotic therapy (including the impact of macrolide combination therapy and antibiotic stewardship), and CAP prevention with novel influenza and pneumococcal vaccines. PMID- 26998244 TI - Ahead of the Curve: New Insights into Microtubule Dynamics. AB - Microtubule dynamics are fundamental for many aspects of cell physiology, but their mechanistic underpinnings remain unclear despite 40 years of intense research. In recent years, the continued union of reconstitution biochemistry, structural biology, and modeling has yielded important discoveries that deepen our understanding of microtubule dynamics. These studies, which we review here, underscore the importance of GTP hydrolysis-induced changes in tubulin structure as microtubules assemble, and highlight the fact that each aspect of microtubule behavior is the output of complex, multi-step processes. Although this body of work moves us closer to appreciating the key features of microtubule biochemistry that drive dynamic instability, the divide between our understanding of microtubules in isolation versus within the cellular milieu remains vast. Bridging this gap will serve as fertile grounds of cytoskeleton-focused research for many years to come. PMID- 26998245 TI - Oocyte Maturation and Development. AB - Sexual reproduction is essential for many organisms to propagate themselves. It requires the formation of haploid female and male gametes: oocytes and sperms. These specialized cells are generated through meiosis, a particular type of cell division that produces cells with recombined genomes that differ from their parental origin. In this review, we highlight the end process of female meiosis, the divisions per se, and how they can give rise to a functional female gamete preparing itself for the ensuing zygotic development. In particular, we discuss why such an essential process in the propagation of species is so poorly controlled, producing a strong percentage of abnormal female gametes in the end. Eventually, we examine aspects related to the lack of centrosomes in female oocytes, the asymmetry in size of the mammalian oocyte upon division, and in mammals the direct consequences of these long-lived cells in the ovary. PMID- 26998246 TI - Airway hyperresponsiveness; smooth muscle as the principal actor. AB - Airway hyperresponsiveness (AHR) is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM) contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-alpha promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway. PMID- 26998247 TI - Recent advances in colonoscopy. AB - Colonoscopy is an important and frequently performed procedure. It is effective in the prevention of colorectal cancer and is an important test in the investigation of many gastrointestinal symptoms. This review focuses on developments over the last 5 years that have led to changes in aspects of colonoscopy, including patient preparation, technical factors, therapeutic procedures, safety, and quality. PMID- 26998250 TI - Emerging Concepts in Transesophageal Echocardiography. AB - Introduced in 1977, transesophageal echocardiography (TEE) offered imaging through a new acoustic window sitting directly behind the heart, allowing improved evaluation of many cardiac conditions. Shortly thereafter, TEE was applied to the intraoperative environment, as investigators quickly recognized that continuous cardiac evaluation and monitoring during surgery, particularly cardiac operations, were now possible. Among the many applications for perioperative TEE, this review will focus on four recent advances: three dimensional TEE imaging, continuous TEE monitoring in the intensive care unit, strain imaging, and assessment of diastolic ventricular function. PMID- 26998248 TI - Towards understanding the evolution and functional diversification of DNA containing plant organelles. AB - Plastids and mitochondria derive from prokaryotic symbionts that lost most of their genes after the establishment of endosymbiosis. In consequence, relatively few of the thousands of different proteins in these organelles are actually encoded there. Most are now specified by nuclear genes. The most direct way to reconstruct the evolutionary history of plastids and mitochondria is to sequence and analyze their relatively small genomes. However, understanding the functional diversification of these organelles requires the identification of their complete protein repertoires - which is the ultimate goal of organellar proteomics. In the meantime, judicious combination of proteomics-based data with analyses of nuclear genes that include interspecies comparisons and/or predictions of subcellular location is the method of choice. Such genome-wide approaches can now make use of the entire sequences of plant nuclear genomes that have emerged since 2000. Here I review the results of these attempts to reconstruct the evolution and functions of plant DNA-containing organelles, focusing in particular on data from nuclear genomes. In addition, I discuss proteomic approaches to the direct identification of organellar proteins and briefly refer to ongoing research on non-coding nuclear DNAs of organellar origin (specifically, nuclear mitochondrial DNA and nuclear plastid DNA). PMID- 26998249 TI - Renal protection in cardiovascular surgery. AB - Acute kidney injury (AKI) is one of the most relevant complications after major surgery and is a predictor of mortality. In Western countries, patients at risk of developing AKI are mainly those undergoing cardiovascular surgical procedures. In this category of patients, AKI depends on a multifactorial etiology, including low ejection fraction, use of contrast media, hemodynamic instability, cardiopulmonary bypass, and bleeding. Despite a growing body of literature, the treatment of renal failure remains mainly supportive (e.g. hemodynamic stability, fluid management, and avoidance of further damage); therefore, the management of patients at risk of AKI should aim at prevention of renal damage. Thus, the present narrative review analyzes the pathophysiology underlying AKI (specifically in high-risk patients), the preoperative risk factors that predispose to renal damage, early biomarkers related to AKI, and the strategies employed for perioperative renal protection. The most recent scientific evidence has been considered, and whenever conflicting data were encountered possible suggestions are provided. PMID- 26998251 TI - Ultrahigh-throughput Generation and Characterization of Cellular Aggregates in Laser-ablated Microwells of Poly(dimethylsiloxane). AB - Aggregates of cells, also known as multicellular aggregates (MCAs), have been used as microscale tissues in the fields of cancer biology, regenerative medicine, and developmental biology for many decades. However, small MCAs (fewer than 100 cells per aggregate) have remained challenging to manufacture in large quantities at high uniformity. Forced aggregation into microwells offers a promising solution for forming consistent aggregates, but commercial sources of microwells are expensive, complicated to manufacture, or lack the surface packing densities that would significantly improve MCA production. To address these concerns, we custom-modified a commercial laser cutter to provide complete control over laser ablation and directly generate microwells in a poly(dimethylsiloxane) (PDMS) substrate. We achieved ultra rapid microwell production speeds (>50,000 microwells/hr) at high areal packing densities (1,800 microwells/cm2) and over large surface areas for cell culture (60 cm2). Variation of the PDMS substrate distance from the laser focal plane during ablation allowed for the generation of microwells with a variety of sizes, contours, and aspect ratios. Casting of high-fidelity microneedle masters in polyurethane allowed for non-ablative microwell reproduction through replica molding. MCAs of human bone marrow derived mesenchymal stem cells (hMSCs), murine 344SQ metastatic adenocarcinoma cells, and human C4-2 prostate cancer cells were generated in our system with high uniformity within 24 hours, and computer vision software aided in the ultra-high-throughput analysis of harvested aggregates. Moreover, MCAs maintained invasive capabilities in 3D migration assays. In particular, 344SQ MCAs demonstrated epithelial lumen formation on Matrigel, and underwent EMT and invasion in the presence of TGF-beta. We expect this technique to find broad utility in the generation and cultivation of cancer cell aggregates, primary cell aggregates, and embryoid bodies. PMID- 26998252 TI - Self-Assembled Nanospheres for Encapsulation and Aerosolization of Rifampicin. AB - Rifampicin (RIF) is a benchmark drug for treatment of tuberculosis, but poor bioavailability, prolonged treatment, and pill burden have been linked to therapeutic failure and the development of multidrug resistant strains. To overcome these limitations, this study investigated a method of rifampicin nanoencapsulation and aerosol delivery using a commercial, hand-held nebulizer modified with a nitrogen stream. PMID- 26998253 TI - Antibacterial Low Molecular Weight Cationic Polymers: Dissecting the Contribution of Hydrophobicity, Chain Length and Charge to Activity. AB - The balance of cationicity and hydrophobicity can profoundly affect the performance of antimicrobial polymers. To this end a library of 24 cationic polymers with uniquely low degrees of polymerization was synthesized via Cu(0) mediated polymerization, using three different cationic monomers and two initiators: providing two different hydrocarbon chain tail lengths (C2 and C12). The polymers exhibited structure-dependent antibacterial activity when tested against a selection of bacteria, viz, Staphylococcus aureus ATCC 29213, Klebsiella pneumoniae ATCC 13883, Acinetobacter baumannii ATCC 19606, and Pseudomonas aeruginosa ATCC 27853 as a representative palette of Gram-positive and Gram-negative ESKAPE pathogens. The five best-performing polymers were identified for additional testing against the polymyxin-resistant A. baumannii ATCC 19606R strain. Polymers having the lowest DP and a C12 hydrophobic tail were shown to provide the broadest antimicrobial activity against the bacteria panel studied as evidenced by lower minimum inhibitory concentrations (MICs). An optimal polymer composition was identified, and its mechanism of action investigated via membrane permeability testing against Escherichia coli. Membrane disruption was identified as the most probable mechanism for bacteria cell killing. PMID- 26998254 TI - Quantum dot cluster (QDC)-loaded phospholipid micelles as a FRET probe for phospholipase A2 detection. AB - A simple assay for phospholipase A2 (PLA2) enzyme was developed based on a fluorescence resonance energy transfer (FRET) probe using the quantum dot cluster (QDC)-loaded phospholipid micelles. The probe was prepared by encapsulating many small hydrophobic quantum dots (QDs) within the hydrophobic core of micelles that were formed from the coassembly of hydrogenated soy phosphatidylcholine phospholipids (HSPC) and fluorescent lipids (NBD-PC). QDCs formed within the micelle core served as the substrate for NBD fluorescence quenching through FRET. The QDC-loaded micelles showed very low background fluorescence. As the PLA2 enzyme selectively digested lipids, the NBD fluorescence was recovered from its quenched state, leading to the sensitive detection of PLA2. This assay provided a limit of detection (at a signal-to-noise ratio of 3) of 3 U/L for PLA2. In the presence of a PLA2 inhibitor, the fluorescent response of the sensor for PLA2 decreased, indicating that the assay could also be used for screening the PLA2 inhibitors. PMID- 26998255 TI - Importance of the Linker Region in Matrix Metalloproteinase-1 Domain Interactions. AB - Collagenolysis is catalyzed by enzymes from the matrix metalloproteinase (MMP) family, where one of the most studied is MMP-1. The X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP) provided important atomistic information, but few details on the effects of the conformational flexibility on catalysis. In addition, the role of the linker region between the catalytic (CAT) and hemopexin-like (HPX) domains was not defined. In order to reveal the dynamics and correlations of MMP-1 comprehensive atomistic molecular dynamics simulations of an MMP-1*THP complex was performed. To examine the role of the linker region for MMP-1 function simulations with linker regions from MT1-MMP/MMP-14 and MMP-13 replacing the MMP-1 linker region were performed. The MD studies were in good agreement with the experimental observation that in the MMP-1*THP X-ray crystallographic structure MMP-1 is in a "closed" conformation. MD revealed that the interactions of the THP with the both the CAT and HPX domains of MMP-1 are dynamic in nature, and the linker region of MMP-1 influences the interactions and dynamics of both the CAT and HPX domains and collagen binding to MMP-1. PMID- 26998256 TI - Surface Defection Reduces Cytotoxicity of Zn(2-methylimidazole)2 (ZIF-8) without Compromising its Drug Delivery Capacity. AB - Zn(2-methylimidazole)2 (ZIF-8), as one of the most important metal-organic framework (MOF) molecules, is a promising candidate for drug delivery due to its low-density structure, high surface area, and tunable frameworks. However, ZIF-8 exhibits a high cytotoxicity associated with its external hydrophobic surface, which significantly restricts its application in drug delivery and other biomedical applications. Commonly used chemical functionalization methods would convert the hydrophobic surface of ZIF-8 to hydrophilic, but the generated functional groups on its internal surface may reduce its pore sizes or even block its pores. Herein, a surface defection strategy was applied on the external surface of ZIF-8 to enhance its hydrophilicity without reducing or blocking the internal pores. In this approach, mechanical ball-milling was used to incur defects on the external surface of ZIF-8, leading to unsaturated Zn-sites and N sites which subsequently bound H2O molecules in an aqueous environment. Furthermore, hydroxyurea delivery and cell cytotoxicity of ZIF-8 with and without the external surface treatment were evaluated. It was found that 5-min ball milling changed the hydrophobic-hydrophilic balance of ZIF-8, resulting in significantly higher cell viability without compromising its hydroxyurea loading and release capacity. Such a simple mechanical ball-milling followed by water treatment provides a general technique for surface-modification of other MOF molecules, which will undoubtedly magnify their biomedical applications. PMID- 26998257 TI - Basal bodies across eukaryotes series: basal bodies in the freshwater planarian Schmidtea mediterranea. AB - The freshwater planarian Schmidtea mediterranea has recently emerged as a valuable model system to study basal bodies (BBs) and cilia. Planarians are free living flatworms that use cilia beating at the surface of their ventral epidermis for gliding along substrates. The ventral epidermis is composed of multiciliated cells (MCCs) that are similar to the MCCs in the respiratory airways, the brain ventricles, and the oviducts in vertebrates. In the planarian epidermis, each cell assembles approximately eighty cilia that beat in a coordinate fashion across the tissue. The BBs that nucleate these cilia all assemble de novo during terminal differentiation of MCCs. The genome of the planarian S. mediterranea has been sequenced and efficient methods for targeting gene expression by RNA interference are available. Defects induced by perturbing the expression of BB proteins can be detected simply by analyzing the locomotion of planarians. BBs are present in large numbers and in predictable orientation, which greatly facilitates analyses by immunofluorescence and electron microscopy. The great ease in targeting gene expression and analyzing associated defects allowed to identify a set of proteins required for BB assembly and function in planarian MCCs. Future technological developments, including methods for transgenic expression in planarians and in related species, will achieve turning free-living flatworms into powerful model systems to study MCCs and the associated human pathologies. PMID- 26998260 TI - Mitochondrial DNA heteroplasmy in human health and disease. AB - The biomedical literature has extensively documented the functional roles of genetic polymorphisms in concert with well-characterized somatic mutations in the etiology and progression of major metastatic diseases afflicting human populations. Mitochondrial heteroplasmy exists as a dynamically determined co expression of inherited polymorphisms and somatic mutations in varying ratios within individual mitochondrial DNA genomes with repetitive patterns of tissue specificity. Mechanistically, carcinogenic cellular processes include profound alterations of normative mitochondrial function, notably dependence on aerobic and anaerobic glycolysis, and aberrant production and release of lactate, according to a classic theory. Within the translational context of human health and disease, the present review discusses the necessity of establishing critical foci designed to probe multiple biological roles of mitochondrial heteroplasmy in cancer biology. PMID- 26998258 TI - Simulating social-ecological systems: the Island Digital Ecosystem Avatars (IDEA) consortium. AB - Systems biology promises to revolutionize medicine, yet human wellbeing is also inherently linked to healthy societies and environments (sustainability). The IDEA Consortium is a systems ecology open science initiative to conduct the basic scientific research needed to build use-oriented simulations (avatars) of entire social-ecological systems. Islands are the most scientifically tractable places for these studies and we begin with one of the best known: Moorea, French Polynesia. The Moorea IDEA will be a sustainability simulator modeling links and feedbacks between climate, environment, biodiversity, and human activities across a coupled marine-terrestrial landscape. As a model system, the resulting knowledge and tools will improve our ability to predict human and natural change on Moorea and elsewhere at scales relevant to management/conservation actions. PMID- 26998259 TI - A clinical perspective of obesity, metabolic syndrome and cardiovascular disease. AB - The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30-40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5-10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI >= 40 or 35-40 kg/m(2) with other significant co morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists. PMID- 26998261 TI - Prostate cancer markers: An update. AB - As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of the most common techniques used to detect prostate cancer are the digital rectal exam, the transrectal ultrasound, and the use of biomarkers. This review presents an update regarding the field of prostate cancer biomarkers and comments on future biomarkers. Although there is not a lack of research in the field of prostate cancer biomarkers, the discovery of a novel biomarker that may have the advantage of being more specific and effective warrants future scientific inquiry. PMID- 26998262 TI - Epithelial-mesenchymal transition in liver fibrosis. AB - Liver fibrosis is the result of a sustained wound healing response to sustained chronic liver injury, which includes viral, alcoholic and autoimmune hepatitis. Hepatic regeneration is the dominant outcome of liver damage. The outcomes of successful repair are the replacement of dead epithelial cells with healthy epithelial cells, and reconstruction of the normal hepatic structure and function. Prevention of the development of epithelial-mesenchymal transition (EMT) may control and even reverse liver fibrosis. EMT is a critical process for an epithelial cell to undergo a conversion to a mesenchymal phenotype, and is believed to be an inflammation-induced response, which may have a central role in liver fibrosis. The origin of fibrogenic cells in liver fibrosis remains controversial. Numerous studies have investigated the origin of all fibrogenic cells within the liver and the mechanism of the signaling pathways that lead to the activation of EMT programs during numerous chronic liver diseases. The present study aimed to summarize the evidence to explain the possible role of EMT in liver fibrosis. PMID- 26998263 TI - Pleckstrin homology-like domain, family A, member 1 (PHLDA1) and cancer. AB - Pleckstrin homology-like domain, family A, member 1 (PHLDA1) encodes a member of an evolutionarily conserved pleckstrin homology-related domain protein family. It was first identified as a potential transcription factor required for Fas expression and activation-induced apoptosis in mouse T cell hybridomas. The exact molecular and biological functions of PHLDA1 remain to be elucidated. However, its expression is induced by a variety of external stimuli and there is evidence that it may function as a transcriptional activator that acts as a mediator of apoptosis, proliferation, differentiation and cell migration dependent on the cellular type and context. Recently, PHLDA1 has received attention due to its association with cancer. In the present review, the current knowledge of PHLDA1 protein structure, expression regulation and function is summarized. In addition, the current data in the literature is reviewed with regards to the role of PHLDA1 in cancer pathogenesis. PMID- 26998264 TI - Occupational exposure and risk of breast cancer. AB - Breast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer. PMID- 26998265 TI - Role of several histone lysine methyltransferases in tumor development. AB - The field of cancer epigenetics has been evolving rapidly in recent decades. Epigenetic mechanisms include DNA methylation, histone modifications and microRNAs. Histone modifications are important markers of function and chromatin state. Aberrant histone methylation frequently occurs in tumor development and progression. Multiple studies have identified that histone lysine methyltransferases regulate gene transcription through the methylation of histone, which affects cell proliferation and differentiation, cell migration and invasion, and other biological characteristics. Histones have variant lysine sites for different levels of methylation, catalyzed by different lysine methyltransferases, which have numerous effects on human cancers. The present review focused on the most recent advances, described the key function sites of histone lysine methyltransferases, integrated significant quantities of data to introduce several compelling histone lysine methyltransferases in various types of human cancers, summarized their role in tumor development and discussed their potential mechanisms of action. PMID- 26998267 TI - Association of gamma-glutamyl transferase with premature coronary artery disease. AB - Accumulating evidence from epidemiological studies suggests that higher gamma glutamyl transferase (GGT) levels in the blood are associated with the incident of cardiovascular disease (CVD), including atherosclerosis, and have prognostic importance. However, to the best of our knowledge, the association of the GGT level with premature coronary artery disease (CAD) in an Asian Indian population has not been evaluated. In the present study, 240 (120 unaffected and 120 CAD affected) young subjects (males, <=45 years and females, <=50 years) were selected. The markers assayed were GGT, high-sensitivity C-reactive protein, lipids, secretory phospholipase A2, neopterin, myeloperoxidase, interleukin-6, cystatin-C, tumor necrosis factor-like weak inducer of apoptosis and lipoprotein (a). The plasma GGT levels in these subjects showed a positive correlation with quantitative variables, such as waist circumference, triglycerides, neopterin levels and cross-sectional correlation with qualitative variable smoking. The findings suggest that the subjects in the highest tertile of GGT had a 2.1-fold [odds ratio (OR), 2.104; 95% confidence interval (CI), 1.063-4.165; P=0.033] higher risk of developing premature CAD in comparison with the reference tertile. Furthermore, a 1 U/l increase of GGT (on a log scale) increased the OR by 5.2 fold (OR, 5.208; 95% CI, 1.018-24.624; P=0.048) and 7.4-fold (OR, 7.492; 95% CI, 1.221-45.979; P=0.030) on addition of associated risk factors. In conclusion, the elevated plasma GGT levels potentially indicate increased oxidative stress and the risk of developing premature CAD. Therefore, these findings could be potentially used in the risk stratification of premature CAD following further evaluation. PMID- 26998266 TI - XB130: A novel adaptor protein in cancer signal transduction. AB - Adaptor proteins are functional proteins that contain two or more protein-binding modules to link signaling proteins together, which affect cell growth and shape and have no enzymatic activity. The actin filament-associated protein (AFAP) family is an important member of the adaptor proteins, including AFAP1, AFAP1L1 and AFAP1L2/XB130. AFAP1 and AFAP1L1 share certain common characteristics and function as an actin-binding protein and a cSrc-activating protein. XB130 exhibits certain unique features in structure and function. The mRNA of XB130 is expressed in human spleen, thyroid, kidney, brain, lung, pancreas, liver, colon and stomach, and the most prominent disease associated with XB130 is cancer. XB130 has a controversial effect on cancer. Studies have shown that XB130 can promote cancer progression and downregulation of XB130-reduced growth of tumors derived from certain cell lines. A higher mRNA level of XB130 was shown to be associated with a better survival in non-small cell lung cancer. Previous studies have shown that XB130 can regulate cell growth, migration and invasion and possibly has the effect through the cAMP-cSrc-phosphoinositide 3-kinase/Akt pathway. Except for cancer, XB130 is also associated with other pathological or physiological procedures, such as airway repair and regeneration. PMID- 26998269 TI - Chronic exposure of low dose salinomycin inhibits MSC migration capability in vitro. AB - Salinomycin is a polyether antiprotozoal antibiotic that is used as a food additive, particularly in poultry farming. By consuming animal products, there may be a chronic human exposure to salinomycin. Salinomycin inhibits the differentiation of preadipocytes into adipocytes. As human mesenchymal stem cells (MSC) may differentiate into different mesenchymal cells, it thus appeared worthwhile to investigate whether chronic salinomycin exposure impairs the functional properties of MSC and induces genotoxic effects. Bone marrow MSC were treated with low-dose salinomycin (100 nM) (MSC-Sal) for 4 weeks, while the medium containing salinomycin was changed every other day. Functional changes were evaluated and compared to MSC without salinomycin treatment (MSC-control). MSC-Sal and MSC-control were positive for cluster of differentiation 90 (CD90), CD73 and CD44, and negative for CD34. There were no differences observed in cell morphology or cytoskeletal structures following salinomycin exposure. The differentiation into adipocytes and osteocytes was not counteracted by salinomycin, and proliferation capability was not inhibited following salinomycin exposure. The migration of MSC-Sal was attenuated significantly as compared to the MSC-control. There were no genotoxic effects after 4 weeks of salinomycin exposure. The present study shows an altered migration capacity as a sign of functional impairment of MSC induced by chronic salinomycin exposure. Further in vitro toxicological investigations, particularly with primary human cells, are required to understand the impact of chronic salinomycin consumption on human cell systems. PMID- 26998270 TI - An examination of co-infection in acute gastroenteritis and histo-blood group antigens leading to viral infection susceptibility. AB - The aim of the present study was to evaluate co-infection in the gastrointestinal tract in terms of viruses, bacteria and the ABO blood group. We hypothesized that a combination of norovirus (NV) and bacteria in the gastrointestinal tract could affect the likelihood of an individual to contracting NV. Histo-blood group antigens (HBGAs) are considered to act as receptors that can lead to NV susceptibility. In addition to genetics, co-infection in the gastrointestinal tract may be associated with this mechanism. A total of 370 patients with acute gastroenteritis presenting with diarrhea (14-89 years) were recruited. The male/female ratio was 20/17. Single infection (bacteria or virus), co-infection with two viruses, and co-infection with one virus and one bacterium were statistically analyzed. In total, 88 of the 376 subjects (23.4%) were positive for one virus, and 50 (13.3%) were positive for one bacterium. Co-transfection with bacteria and a virus were detected in 46 (47.9%) of the 96 bacterial gastroenteritis cases. Statistical analysis revealed that co-infection of bacteria and NV was not significant in all viral infections (P=0.768). In terms of the ABO histo-blood group type and NV infection, the frequency in the O type was not significantly increased (P=0.052). Co-infection of bacteria and a virus occurred frequently in the gastrointestinal tract. The ABO blood phenotype expression was not a significant factor in NV infection in the present case series and the results did not suggest an affinity of NV for specific bacteria. PMID- 26998268 TI - Ventricular anti-arrhythmic effects of heptanol in hypokalaemic, Langendorff perfused mouse hearts. AB - Ventricular arrhythmic and electrophysiological properties were examined during normokalaemia (5.2 mM [K+]), hypokalaemia (3 mM [K+]) or hypokalaemia in the presence of 0.1 or 2 mM heptanol in Langendorff-perfused mouse hearts. Left ventricular epicardial or endocardial monophasic action potential recordings were obtained during right ventricular pacing. Hypokalaemia induced ventricular premature beats (VPBs) in 5 of 7 and ventricular tachycardia (VT) in 6 of 7 hearts (P<0.01), prolonged action potential durations (APD90) from 36.2+/-1.7 to 55.7+/-2.0 msec (P<0.01) and shortened ventricular effective refractory periods (VERPs) from 44.5+/-4.0 to 28.9+/-3.8 msec (P<0.01) without altering conduction velocities (CVs) (0.17+/-0.01 m/sec, P>0.05), reducing excitation wavelengths (lambda, CV * VERP) from 7.9+/-1.1 to 5.1+/-0.3 mm (P<0.05) while increasing critical intervals (CI, APD90-VERP) from -8.3+/-4.3 to 26.9+/-2.0 msec (P>0.001). Heptanol (0.1 mM) prevented VT, restored effective refractory period (ERP) to 45.2+/-2.9 msec without altering CV or APD, returning lambda to control values (P>0.05) and CI to 8.4+/-3.8 msec (P<0.05). Heptanol (2 mM) prevented VPBs and VT, increased ERP to 67.7+/-7.6 msec (P<0.05), and reduced CV to 0.11+/-0.1 m/sec (P<0.001) without altering APD (P>0.05), returning lambda and CI to control values (P>0.05). Anti-arrhythmic effects of heptanol during hypokalaemia were explicable by ERP changes, scaling lambda and CI. PMID- 26998271 TI - RhoA activity increases due to hypermethylation of ARHGAP28 in a highly liver metastatic colon cancer cell line. AB - Certain cell lines exhibit metastatic ability (highly metastatic cell lines) while their parent cell lines have no metastatic ability. Differences in methylation, which are not derived from differences in the gene sequence between cell lines, were extensively analyzed. Using an established highly metastatic cell line, KM12SM, and its parent cell line, KM12C, differences in the frequency of methylation were analyzed in the promoter regions of ~480,000 gene sites using Infinium HumanMethylation450. The promoter region of the Rho GTPase-activating protein 28 (ARHGAP28) gene was the most markedly methylated region in KM12SM compared with KM12C. ARHGAP28 is a GTPase-activating protein (GAP), and it converts activated RhoA to inactivated RhoA via GTPase. RhoA activity was compared between these two cell lines. The activated RhoA level was compared using western blot analysis and G-LISA. The activated RhoA level was higher in KM12SM compared to KM12C for western blot analysis and G-LISA analysis. RhoA is a protein involved in cytoskeleton formation and cell motility. RhoA, for which ARHGAP28 acts as a GAP, is possibly a factor involved in the metastatic ability of cancer. PMID- 26998272 TI - Effect of low-intensity focused ultrasound on endothelin-1, nitrogen monoxide and oxytocin receptor in the uterine tissues of Sprague-Dawley rats following abortion. AB - The aim of the present study was to investigate the effect of low-intensity focused ultrasound on endothelin-1 (ET-1), nitrogen monoxide (NO) and oxytocin receptor (OXTR) levels in the uterine tissues of Sprague-Dawley (SD) rats following abortion. A total of 30 SD rats undergoing complete abortion were randomly divided into ultrasound irradiation and sham irradiation groups (15 rats per group). The rats in the ultrasound irradiation group were treated with low intensity ultrasound (sound intensity, 2 W/cm2; frequency, 0.8 MHz) for 30 min daily for 5 consecutive days, and those in the sham irradiation group received sham treatment. The uterine tissue was removed to measure the levels of ET-1, NO and OXTR using the enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The ET-1 level in the uterine tissues was significantly higher in the ultrasound irradiation group compared to the sham irradiation group (P<0.05); however, the NO level was similar in the 2 groups (P>0.05). In the uterine myometrium and endometrium, the strong positive expression of OXTR was observed in the ultrasound irradiation group, which was significantly higher compared to the sham irradiation group (P<0.05). Low-intensity ultrasound could promote uterine involution by increasing ET-1 levels, modifying the balance of ET-1 and NO, and enhancing the expression of OXTR in the uterine myometrium and endometrium. PMID- 26998273 TI - 4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4. AB - The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expression level was downregulated by siRNA. The POLD4 protein levels in the A549 cells decreased following treatment with 4NQO; however, MG132 could reverse this phenotype. Downregulation of the POLD4 expression by siRNA enhanced A549 cell sensitivity to 4NQO, but not to Taxol. In conclusion, 4NQO affects human lung adenocarcinoma A549 cells by regulating the expression of POLD4. PMID- 26998274 TI - Synergistic antioxidant activity of resveratrol with genistein in high-glucose treated Madin-Darby canine kidney epithelial cells. AB - Resveratrol (Re), a stilbenoid, is associated with a potential benefit in controlling certain biomarkers in type II diabetes. Genistein (Ge), a phytoestrogen, may act as an antioxidant and thus may diminish damaging effects of free radicals in tissues. In the present study, a potential synergistic antioxidant effect of an Re/Ge combination on high-glucose (HG) incubation in Madin-Darby canine kidney (MDCK) epithelial cells was evaluated. Compared with the treatment of Re or Ge alone, the Re/Ge combination synergistically decreased intracellular reactive oxygen species (ROS) and hydroxyl radicals in MDCK cells. This synergistic antioxidant effect correlated with the inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and an increase in gamma-glutamylcysteine synthetase expression. In addition, mitochondrial complex I, NADPH oxidase, xanthine oxidase and lipoxygenase contributed towards ROS overproduction when the MDCK cells were incubated with HG. In conclusion, the Re/Ge combination synergistically enhanced the antioxidant effect in HG-incubated kidney cells, possibly through an enhanced antioxidant regulation mechanism. The Re/Ge combination may be a potential benefit against oxidative stress in diabetes mellitus. PMID- 26998275 TI - Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis. AB - Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6+/-22 vs. 35.6+/-15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and SLE susceptibility. PMID- 26998276 TI - Antitumor effect of a polysaccharide isolated from Phellinus pullus as an immunostimulant. AB - The antitumor function of fungal polysaccharides is a popular area of interest in the research field due to their high efficiency and low side effects. The main mechanism of fungal polysaccharides is immune enhancement. The polysaccharose (APS-3) was extracted from the fruit body of Phellinus pullus. The proliferation inhibition to mouse sarcoma 180 (S180) tumor cells was studied by the MTT method. Mice models of transplanted S180 tumor were established and treated with APS-3 to verify the antitumor activity in vivo. Natural killer (NK) and lymphokine activated killer (LAK) cytotoxicities of the mice were evaluated by the lactate dehydrogenase method. APS-3 can significantly inhibit the proliferation of the S180 cells. Cells could be completely inhibited by 1.6 mg/ml APS-3 after 24 h treatment. After 18 days of treatment, the antitumor rate of the high-dose group was 85.47%. Histopathology detection showed that for the APS-3-treated mice, the tumor cells dissolved, and exhibited a large range of structureless necrotic areas. NK and LAK cytotoxicities of the APS-3 treated mice increased by 61.85 and 56.16%, respectively, compared with the normal control mice. APS-3 can be used as an antitumor agent by way of immune enhancement. PMID- 26998277 TI - Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells. AB - The phosphoinositide 3-kinase/Akt pathway activation commonly occurs in various types of human cancer and has an important role in chemoresistance. Combination of traditional chemotherapy drugs and molecular-targeted agents is a promising strategy for cancer therapy, which has shown enhanced cytotoxicity and lower drug resistance. The present study found that the Akt inhibitor, MK-2206, can increase the effect of cisplatin in the gastric cancer cell line AGS, which has higher Akt phosphorylation, but exhibited a poor combination effect in MKN-45 and MGC-803 cells, which have limited Akt activation. The MTT assay demonstrated that sequential treatment of cisplatin, followed by the Akt inhibitor, MK-2206, caused a synergistic effect of proliferation inhibition, and the apoptosis assay by propidium iodide/fluorescein isothiocyanate staining also showed that combination treatment induced more apoptosis compared to the monotherapy groups. Using western blot analysis, MK-2206 was shown to significantly suppress the phosphorylation of Akt (Ser473), however, the expression of total Akt remained the same, and the combination treatment also increased the expression of cleaved poly adenosine diphosphate ribose polymerase, which contributed to apoptosis. PMID- 26998278 TI - Association of the nibrin gene (NBN) variants with breast cancer. AB - Nibrin, encoded by the NBN gene, participates in DNA repair. Mutations in the NBN gene lead to Nijemen breakage syndrome, which may result in several types of diseases, particularly susceptibility to cancer, including breast cancer. Polymorphic variants and defective mutations occurring in the NBN gene increase the risk of breast cancer through the double-stranded break repair mechanism. The aim of the present study was to investigate a possible association between breast cancer and NBN genetic variants, NBN 924 T>C, 8360 G>C and 30537 G>C, in women with breast cancer. Locus-specific primers were designed to study 3 genetic variants in DNA samples isolated from peripheral blood samples of 101 women with breast cancer and 115 healthy controls. Subsequently, 3 polymerase chain reaction restriction fragment length polymorphism methods were performed and the obtained results were statistically analysed. The NBN gene 924 T>C variant was found to be significantly associated with breast cancer (chi2=5.722, P=0.017). There were no statistically significant differences between cases and controls in the NBN gene 8360 G>C variant (chi2=1,125, P=0.570) or the NBN gene 30537 G>C variant (chi2=4.301, P=0.116). In conclusion, the NBN gene 924 T>C variant may be a genetic risk factor for breast cancer development in women with breast cancer. PMID- 26998279 TI - Possibility of one-stage surgery to reconstruct bone defects using the modified Masquelet technique with degradable calcium sulfate as a cement spacer: A case report and hypothesis. AB - In addition to autologous bone graft, vascularized fibular autograft and Ilizarov bone transfer, the Masquelet technique is another effective method to reconstruct bone defects. This technique was initially proposed in 1986 and consists of two stages. At the first stage, radical debridement is required and subsequently, a polymethylmethacrylate (PMMA) cement spacer is implanted at the site of the bone defects. At the second stage, when the PMMA-induced membrane is formed 6-8 weeks later, the cement spacer is carefully removed in order to not disturb the induced membrane and the bone graft is performed to fill the bone defects. Although this technique has resulted in satisfactory outcomes in the reconstruction of bone defects, the PMMA spacer used to induce membrane is not degradable and requires surgical removal. In recent years, calcium sulfate has been used as a localized antibiotic delivery vehicle and bone substitute due to its superiorities over PMMA, particularly its completely degradable nature. The present study identified that calcium sulfate can also induce the formation of a membrane. In addition, we hypothesized that the degradability of calcium sulfate may allow one-stage reconstruction of bone defects. The current study presents a clinical case report and review of the literature. PMID- 26998280 TI - Expression of calcitonin gene-related peptide, adenosine A2a receptor and adenosine A1 receptor in experiment rat migraine models. AB - A migraine is a disabling neurovascular disorder characterized by a unilateral throbbing headache that lasts from 4 to 72 h. The headache is often accompanied by nausea, vomiting, phonophobia and photophobia, and may be worsened by physical exercise. The trigeminovascular system (TVS) is speculated to have an important role in migraines, although the pathophysiology of this disorder remains to be elucidated. Trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (TNC) are important components of the TVS. Several clinical cases have provided evidence for the involvement of the brainstem in migraine initiation. Electrical stimulation of the trigeminal ganglion (ESTG) in rats can activate TVS during a migraine attack. Calcitonin gene-related peptide (CGRP) is an important vasoactive compound produced following TVS activation. Numerous studies have revealed that adenosine and its receptors have an important role in pain transmission and regulation process. However, only a few studies have examined whether adenosine A2a receptor (A2aR) and adenosine A1 receptor (A1R) are involved in migraine and nociceptive pathways. In the present study, CGRP, A2aR and A1R expression levels were detected in the TG and TNC of ESTG models through reverse transcription-quantitative polymerase chain reaction and western blot analysis. Tianshu capsule (TSC), a type of Chinese medicine, was also used in the ESTG rat models to examine its influence on the three proteins. Results demonstrated that CGRP, A2aR and A1R mediated pain transmission and the regulation process during migraine and the expression of the three proteins was regulated by TSC. PMID- 26998281 TI - Effect of a traditional herbal medicine, hangekobokuto, on the sensation of a lump in the throat in patients with respiratory diseases. AB - The sensation of a lump in the throat (SLT) is not a rarely encountered symptom. The etiology of SLT appears to be multifactorial, and the psychological characteristics, stress and pressure of a psychiatric disorder may be significant factors in SLT. Hangekobokuto, one of the traditional herbal medicines, is a known drug that has an effect on SLT. The efficacy of a short-term hangekobokuto treatment on SLT was evaluated. To assess whether a 2-week prescription of hangekobokuto improves SLT mainly in patients with respiratory diseases, a retrospective study was performed between April 2013 and August 2015. During the study period, a total of 43 patients were treated with hangekobokuto. Twelve (27.9%) of the 43 patients were reported to experience completely effective treatment (SLT completely disappeared), and 14 (32.6%) experienced moderately effective treatment (25-99% SLT disappeared). Patients with bronchial asthma and those without a medical history of respiratory disease exhibited a good response to hangekobokuto. No specific predictive factor of the response to hangekobokuto on SLT was identified in the multivariate regression analysis. Therefore, the present results suggested that hangekobokuto could be one of the treatment choices for uncontrolled SLT. PMID- 26998282 TI - LKB1/AMPK pathway mediates resistin-induced cardiomyocyte hypertrophy in H9c2 embryonic rat cardiomyocytes. AB - Resistin has been previously demonstrated to induce cardiac hypertrophy, however, the underlying molecular mechanisms of resistin-induced cardiac hypertrophy remain unclear. Using H9c2 cells, the present study investigated the liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway for a potential role in mediating resistin-induced cardiomyocyte hypertrophy. Treatment of H9c2 cells with resistin increased cell surface area, protein synthesis, and expression of hypertrophic marker brain natriuretic peptide and beta-myosin heavy chain. Treatment with metformine attenuated these effects of resistin. Furthermore, treatment with resistin decreased phosphorylation of LKB1 and AMPK, whereas pretreatment with metformin increased phosphorylation of LKB1 and AMPK that is reduced by resistin. These results suggest that resistin induces cardiac hypertrophy through the inactivation of the LKB1/AMPK cell signaling pathway. PMID- 26998283 TI - Meta-analyses of treatment standards for pancreatic cancer. AB - Pancreatic cancer is the most lethal common cancer with an estimated 5-year survival rate of 6-7% (across all stages). The only potential curative therapy is surgical resection in those with localized disease. Adjuvant (postoperative) therapy confers a survival advantage over postoperative observation alone. Neoadjuvant (preoperative) therapy offers the potential to downstage initially unresectable tumors for resection, sterilize resection margins and decrease locoregional recurrence, and identify a subset of patients with aggressive disease for whom surgery will not be beneficial. Induction chemotherapy followed by consolidation chemoradiation is another recommended approach in those with locally advanced disease. For those who cannot be downstaged, cannot tolerate surgery, or were diagnosed with metastatic disease, treatment remains palliative with chemotherapy being a critical component of this approach. Recently, intensive combination chemotherapy has been shown to improve survival rates in comparison to gemcitabine alone in advanced disease. The past few decades have afforded an accumulation of high-level evidence regarding neoadjuvant, adjuvant and palliative therapies in pancreatic cancer. There are numerous reviews discussing recent retrospective studies, prospective studies and randomized controlled trials in each of these areas. However, reviews of optimal and recommended treatment strategies across all stages of pancreatic cancer that focus on the highest levels of hierarchical evidence, such as meta-analyses, are limited. The discussion of novel therapeutics is beyond the scope of this review. However, an extensive and the most current collection of meta-analyses of first line systemic and locoregional treatment options for all stages of pancreatic cancer to date has been accumulated. PMID- 26998285 TI - Sonic hedgehog signaling in hepatocellular carcinoma: A pilot study. AB - Hedgehog signaling is involved in the pathogenesis of several tumor types; however, its role in hepatocellular carcinoma (HCC) has not been fully elucidated. Biomarkers that reflect tumor aggressiveness are of potential value in selecting HCC patients for liver transplantation (LT). The aim of the present study was to assess the tissue expression of sonic hedgehog (Shh) biomarkers in HCC and surrounding non-tumorous liver tissue, and to correlate this expression with HCC recurrence following LT. Patients who underwent LT for HCC at the Cleveland Clinic (Cleveland, OH, USA) between 2002 and 2006 were randomly selected for analysis. Tissue samples were retrieved from the explanted tumorous livers. Routine immunohistochemistry was used to detect three specific Shh pathway biomarkers: The ligand Shh, the receptor patched-1 (Ptch) and the transcription factor glioma-associated oncogene homolog 1 (Gli1). Computerized quantitative analysis was used to evaluate the expression levels of these markers in HCC and surrounding non-tumorous liver tissue. Analysis of variance was used to compare the differential tissue expression between patients with and those without HCC recurrence. A time-to-event analysis was performed to assess the association of hedgehog biomarker expression with the risk of HCC recurrence following LT. A total of 53 tissue specimens from 21 patients were analyzed. The mean patient age was 57+/-8 years and 86% of the patients were male. A total of 62% patients had hepatitis C virus infection, 14% had hepatitis B virus infection, 43% had alcoholic cirrhosis and 91% fulfilled the Milan criteria at the time of LT. The average follow-up time after LT was 36+/-15 months, during which 19% of the patients developed HCC recurrence and 29% died. Shh, Ptch and Gli1 were detected in the HCC tissues of all the patients. Ptch was overexpressed in HCC compared with the surrounding non-tumorous tissue. The statistical power of this study was unable to associate Shh pathway markers with HCC recurrence following LT. In a proof-of-concept study, we demonstrated tissue expression of three Shh biomarkers within HCC tumors, and also identified differences in Ptch expression between tumor and surrounding non-tumorous tissue. Further larger studies are required to assess the utility of these biomarkers in HCC. PMID- 26998286 TI - Stromal expression of matrix metalloproteinase 2 in cancer-associated fibroblasts is strongly related to human epidermal growth factor receptor 2 status in invasive breast carcinoma. AB - The peritumoral stroma and cancer-associated fibroblasts (CAFs) have been suggested to play an important role in breast tumorigenesis. The specific immunohistochemical characteristics of the stromal component according to the breast carcinoma subtype surrogates of molecular classes is poorly understood. In the present study, immunohistochemical staining was used to evaluate the expression of matrix metalloproteinase 2 (MMP2), which is one of the most important proteins considered to facilitate tumor invasion, in a series of invasive breast carcinomas according to subtype: Luminal A, luminal B, luminal HER2, HER2-enriched and triple-negative. A significant increase in MMP2 expression was demonstrated in tumors known to exhibit a more aggressive metastatic behavior, such as luminal HER2 (37%), HER2-enriched (30%) and triple negative tumors (17%), compared with the luminal A (6%) or luminal B (13%) subtypes. Our data indicated that the CAFs associated with different breast subtypes exhibit different specific properties to facilitate tumor invasion. PMID- 26998287 TI - Evaluation of febrile neutropenic episodes in adult patients with solid tumors. AB - The clinical use of cytotoxic chemotherapeutic agents has increased survival in cancer patients. However, treatment-associated bone marrow suppression and neutropenia often render patients prone to life-threatening infections. The aim of this study was to evaluate episodes of febrile neutropenia (FN) in patients with solid tumors, and identify the microorganisms and the factors affecting mortality. A total of 100 primary febrile attacks in cancer patients who were followed up at the Department of Oncology of the Akdeniz University Medical Faculty Hospital between January, 2011 and May, 2012, were retrospectively investigated. FN attacks were classified in three groups as follows: Fever of unknown origin, clinically documented infections and microbiologically documented infections. We found that prolonged neutropenia, Multinational Association for Supportive Care in Cancer (MASCC) score <21 and the presence of metastasis increased mortality. We also compared the three groups of infection categories according to mortality rate, but did not observe any significant differences among these groups. Patients with malignancies should be assessed individually during the FN episodes. It is crucial to keep possible infectious pathogens in mind and evaluate the MASCC score, neutropenia duration and metastatic status of the patients, and start empirical antibiotic therapy immediately. PMID- 26998288 TI - Triple-negative breast cancer exhibits a favorable response to neoadjuvant chemotherapy independent of the expression of topoisomerase IIalpha. AB - The present study retrospectively analyzed the utility of topoisomerase IIalpha expression as a prognostic marker to predict the neoadjuvant chemotherapeutic response and survival among different breast cancer subtypes. The patients were subtyped and the expression of topoisomerase IIalpha was determined using immunohistochemistry. All patients (n=147) received an anthracycline-containing regimen preoperatively, and 139 (95%) patients also received docetaxel. Of the 147 patients, 25 (17%) were triple-negative and 20 (17%) were human epidermal growth factor receptor 2 (HER2)-positive. Among these subtypes, a significantly higher a rate (P<0.0001) and higher incidence of topoisomerase IIalpha expression (P=0.036) were observed compared with that in the hormone receptor-positive and HER2-negative breast cancer types. However, the expression of topoisomerase IIalpha revealed no correlation with the treatment response or survival in any of the subtypes. Therefore, these results indicated that the favorable response to anthracycline-containing chemotherapy among triple-negative and HER2-positive breast cancer was independent of the expression of topoisomerase IIalpha. PMID- 26998289 TI - Hodgkin's lymphoma as a rare variant of Richter's transformation in chronic lymphocytic leukemia: A case report and review of the literature. AB - Richter's transformation induces an aggressive clinical course in chronic lymphocytic leukemia (CLL). In the majority of cases, Richter's transformation manifests itself as a high-grade B-cell non-Hodgkin's lymphoma (B-NHL). However, other histological types, such as classical Hodgkin lymphoma (cHL), lymphoblastic lymphoma, hairy cell leukemia and high-grade T-cell NHL have been described previously. The present study reports a rare case of CLL with transformation into classical Hodgkin's lymphoma (cHL). The common clonal origin of CLL and cHL was documented by immunoglobulin gene rearrangement analysis performed using multiplex polymerase chain reaction. Following a review of the literature, treatment of secondary Hodgkin's lymphoma is discussed, and prognosis is often poor. PMID- 26998284 TI - Conserved molecular mechanisms underlying the effects of small molecule xenobiotic chemotherapeutics on cells. AB - For proper determination of the apoptotic potential of chemoxenobiotics in synergism, it is important to understand the modes, levels and character of interactions of chemoxenobiotics with cells in the context of predicted conserved biophysical properties. Chemoxenobiotic structures are studied with respect to atom distribution over molecular space, the predicted overall octanol-to-water partition coefficient (Log OWPC; unitless) and molecular size viz a viz van der Waals diameter (vdWD). The Log OWPC-to-vdWD (nm-1 ) parameter is determined, and where applicable, hydrophilic interacting moiety/core-to-vdWD (nm-1 ) and lipophilic incorporating hydrophobic moiety/core-to-vdWD (nm-1 ) parameters of their part-structures are determined. The cellular and sub-cellular level interactions of the spectrum of xenobiotic chemotherapies have been characterized, for which a classification system has been developed based on predicted conserved biophysical properties with respect to the mode of chemotherapeutic effect. The findings of this study are applicable towards improving the effectiveness of existing combination chemotherapy regimens and the predictive accuracy of personalized cancer treatment algorithms as well as towards the selection of appropriate novel xenobiotics with the potential to be potent chemotherapeutics for dendrimer nanoparticle-based effective transvascular delivery. PMID- 26998290 TI - A phase II, randomized study of aprepitant in the prevention of chemotherapy induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients. AB - The present study aimed to study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer (CRC), and comprised a multicenter, phase II, open-label, randomized, parallel comparative study conducted as part of the Kagoshima aprepitant study for colon cancer in Japan. Patients with advanced or recurrent CRC were treated with standard MEC regimens (FOLFOX, XELOX or FOLFIRI) and received either standard chemotherapy [5 hydroxytryptamine-3 receptor antagonist (5-HT3RA) + dexamethasone] or aprepitant regimen chemotherapy (5-HT3 RA + reduced-dose dexamethasone + aprepitant). The primary endpoint of the present study was the proportion of patients who achieved a complete response (CR) during the overall, acute, and delayed phases of the first planned chemotherapy cycle. Secondary endpoints were complete protection, the proportions of patients without emetic episodes or nausea, patients with no more than moderate nausea during the overall, acute and delayed phases, and the time to treatment failure. The CR rates in the overall, acute and delayed phases were similar in the aprepitant and the standard-regimen groups. Additionally, there were no significant differences in secondary endpoints between the two groups. In summary, aprepitant in combination with 5-HT3 RA and reduced-dose corticosteroids was well tolerated and effective in preventing CINV associated with moderately emetogenic antitumor agents in Japanese patients with CRC. PMID- 26998291 TI - Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival. AB - Experimental and epidemiological data support the potential activity of acetaminophen against ovarian cancer (OVCA). In this study, we sought to confirm the activity of acetaminophen in OVCA cell lines and to investigate the molecular basis of response. A total of 16 OVCA cell lines underwent pretreatment (baseline) genome-wide expression measurements and were then treated with and analyzed for acetaminophen sensitivity. Pearson's correlation analysis was performed to identify genes that were associated with OVCA acetaminophen response. The identified genes were subjected to pathway analysis, and the expression of each represented pathway was summarized using principal component analysis. OVCA acetaminophen response pathways were analyzed in 4 external clinico-genomic datasets from 820 women for associations with overall survival from OVCA. Acetaminophen exhibited antiproliferative activity against all tested OVCA cell lines, with half maximal inhibitory concentration values ranging from 63.2 to 403 uM. Pearson's correlation followed by biological pathway analysis identified 13 pathways to be associated with acetaminophen sensitivity (P<0.01). Associations were observed between patient survival from OVCA and expression of the following pathways: Development/angiotensin signaling via beta-arrestin (P=0.04), protein folding and maturation/angiotensin system maturation (P=0.02), signal transduction/c-Jun N-terminal kinase (JNK) pathway (P=0.03) and androstenedione and testosterone biosynthesis and metabolism (P=0.02). We confirmed that acetaminophen was active against OVCA cells in vitro. Furthermore, we identified 4 molecular signaling pathways associated with acetaminophen response that may also affect overall survival in women with OVCA, including the JNK pathway, which has been previously implicated in the mechanism of action of acetaminophen and is predictive of decreased survival in women with OVCA. PMID- 26998292 TI - Lymphoepithelioma-like gastric carcinoma located in the lesser curvature of the gastric body: A case report and review of the literature. AB - Lymphoepithelioma-like gastric carcinoma (LELC) is a type of Epstein-Barr virus (EBV)-associated gastric cancer, characterized by the presence of a lymphoid stroma with cells arranged primarily in microalveolar, thin trabecular and primitive tubular patterns, or isolated cells. In situ hybridization is usually used to confirm the presence of EBV. LELC is a rare type of cancer, with an incidence of 1-4% among all gastric cancers. Despite its rarity, this tumor has attracted attention due to its distinct clinicopathological characteristics and its association with the immune system. This is the report of a rare case of gastric LELC located in the lesser curvature of the gastric body. PMID- 26998293 TI - Metastatic pulmonary calcification misdiagnosed as a fungal infection: A case report. AB - Metastatic pulmonary calcification is a rare lesion, characterized by calcium salt depositing in normal lung tissue. The clinical profile of a case of metastatic pulmonary calcification following renal transplantation was described. A computed tomography scan of the chest revealed ground-glass opacities in bilateral lungs and a node exhibiting a halo in the right upper lobe, which were suspected aspergillus infection. Following examination and therapy, the results of lung biopsy revealed metastatic pulmonary calcification. Although metastatic pulmonary calcification was reported in renal failure patients previously, metastatic pulmonary calcification with cavity lesions has never, to the best of our knowledge, been previously reported. The aim of the present report was to improve the understanding of metastatic pulmonary calcification. PMID- 26998294 TI - Skin rash in the intensive care unit: Stevens-Johnson syndrome, toxic epidermal necrolysis, or a rare manifestation of a hidden cutaneous malignancy: A case report. AB - Skin rashes are infrequently encountered in the intensive care units, either as a result or as a cause of admission. The entities of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of desquamating skin diseases that have multiple etiologies, the most common being drug-related reactions; very rarely, the cause may be cutaneous malignancies. We herein present a unique case of a 54-year-old male patient with psoriasis treated with methotrexate, who presented with a cellulitis-like clinical picture, then developed a severe progressive systemic inflammatory response syndrome, and progressed clinically to SJS, then TEN even after discontinuing the antibiotics and methotrexate. A skin biopsy demonstrated an aggressive and rapidly progressing T-cell lymphoma. The present case highlights the necessity of skin biopsy when encountering SJS and TEN in the ICU in order to identify potentially treatable/controllable causes. Although it appeared reasonable to correlate TEN solely to medications, the skin biopsies clearly demonstrated an aggressive T cell skin lymphoma. In a patient with a better general condition it may have been helpful to treat this malignancy. TEN is a life-threatening condition and skin biopsy is the cornerstone of diagnosis, despite the presence of multiple risk factors and the typical physical findings of a drug-induced reaction. PMID- 26998295 TI - Primary squamous cell carcinoma of the seminal vesicle: A case report. AB - Primary squamous cell carcinoma (SCC) is extremely rare in the seminal vesicle. A 26-year-old male patient presented with complaints of difficulty in urination for 10 years and gross hematuria for 7 months. Ultrasonography and computed tomography imaging demonstrated a large mixed solid/cystic mass lesions in the rectovesical pouch. The mass was completely resected with the open approach and was verified as a primary SCC of the seminal vesicle by post-surgical histopathological examination. Pelvic metastases were detected 28 months after the surgery. This is the third reported case of primary SCC of the seminal vesicle, and the first one in a young patient. Early diagnosis and treatment are crucial for primary SCC of the seminal vesicle. PMID- 26998296 TI - Comparison of mammography and ultrasound in detecting residual disease following bioptic lumpectomy in breast cancer patients. AB - Surgical biopsy is a method for diagnosing breast cancer. The aim of this study was to prospectively evaluate the relative accuracies of mammography (MMG) and ultrasound (US) in predicting residual disease following bioptic lumpectomy. Each prediction method was compared with the gold standard of surgical pathology. The results of MMG and US from 312 consecutive breast cancer patients diagnosed by surgical excision were analyzed. All the patients underwent re-excision mastectomy or lumpectomy and the imaging results were compared with the histopathological findings. The accuracy and sensitivity of each modality were investigated. A total of 312 patients with 312 primary breast cancers were investigated. Residual disease was identified in 118 patients. Of the 118 cases with residual disease, MMG and US were able to detect 77 (65.3%) and 32 (27.1%), respectively (chi-square P<0.001). MMG was also more sensitive compared with US in estimating residual ductal carcinoma in situ (DCIS) (94.2 vs. 33.3%, respectively; P<0.001). MMG was more accurate compared with US in detecting residual disease following bioptic lumpectomy and the diagnostic accuracy of MMG was associated with the presence of residual DCIS. PMID- 26998297 TI - Efficacy of first-line erlotinib in non-small cell lung cancer patients undergoing dose reduction and those with a low body surface area: A population based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group. AB - The aim of the present study was to evaluate the efficacy of erlotinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), in patients undergoing dose reduction and in those with a low body surface area (BSA). The association between dose reduction, low BSA and efficacy, including response rate, disease control rate, time to treatment failure and overall survival, were evaluated in patients prescribed first-line erlotinib for EGFR mutated non-small cell lung cancer patients between April 2012 and March 2015. A total of 22 patients received first-line erlotinib during the study period. A dose reduction of erlotinib for the reason of low BSA and poor performance status occurred in 14 (63.6%) of the patients: 6 (27.3%) had initial dose reduction, 6 (27.3%) had dose reduction in their clinical courses, and 2 (9.1%) had both. Dose reduction of erlotinib with the initial dose of erlotinib/BSA was >80 mg/m2, and longest-term prescribed dose of erlotinib/BSA was >50 mg/m2, which may have no association with a survival disadvantage. Dose-reduction estimation studies for TKIs may be crucial, particularly for patients with a low BSA. Future prospective studies and confirmation of these results in population-based retrospective ones investigating the incidence of dose reduction in patients with AEs and those with low BSA may be required for the efficient use of erlotinib in common clinical practice. PMID- 26998298 TI - Volumetric modulated arc radiotherapy of the whole larynx, followed by a single affected vocal cord, for T1a glottic cancer: Dosimetric analysis of a case. AB - Radiation therapy (RT) and endolaryngeal surgery are standard treatments for early-stage glottic cancer. They have closely matched oncological outcomes; however, it is debatable which method is superior in terms of functional outcomes. Several dosimetric studies have demonstrated that, compared with conventional RT, intensity-modulated RT (IMRT) reduces unnecessary radiation of the adjacent normal tissues, including the carotid artery and thyroid gland. However, RT targets the whole larynx, whereas endolaryngeal surgery is a highly focused treatment involving the en bloc resection of a tumor with safety margins. For T1a glottic cancer, in which the tumor is limited to one vocal cord, the technical feasibility of targeting IMRT on the single vocal cord affected has been investigated; however, the clinical feasibility and the possibility of inferior local control remain to be elucidated. In the present case study, IMRT was used to treat the whole larynx first, and then to treat a single vocal cord. The patient in the present study had T1a glottic cancer, and received volumetric modulated arc therapy with a total dose of 63 Gy/28 fractions. The first treatment phase (40.5 Gy/18 fractions) targeted the whole larynx to eliminate subclinical disease. The second treatment phase (22.5 Gy/10 fractions) targeted only the involved vocal cord. During this treatment phase, the exposure of the non-involved right vocal cord, the right carotid artery and the thyroid gland to the radiation was lower compared with the continuation of the initial treatment approach. These findings suggested that changing the target volume from the whole larynx to the affected vocal cord during the course of IMRT is feasible for T1a glottic cancer, and that it may reduce functional side effects while maintaining oncological outcomes. PMID- 26998299 TI - Breast cancer following polyacrylamide hydrogel injection for breast augmentation: A case report. AB - Polyacrylamide hydrogel (PAAG) has been used for several years as an injectable implant for augmentation mammoplasty in China. Although patients who received PAAG injections experienced a number of complications, breast cancer following PAAG injection has been reported only in two cases. In this report, we present a case of breast cancer following PAAG injection for breast augmentation. Our study demonstrated that PAAG injection may increase the risk of breast cancer development. Early-stage breast cancer detection is difficult, since the breast is covered with the indurated injected gel. Thus, PAAG injection for augmentation mammoplasty may negatively affect breast cancer diagnosis and prognosis. PMID- 26998300 TI - Rituximab for refractory subcutaneous Sweet's syndrome in chronic lymphocytic leukemia: A case report. AB - Sweet's syndrome is a neutrophilic dermatosis characterised by sudden onset of fever, neutrophilia, erythematous skin rashes and neutrophilic infiltration of the dermis. Subcutaneous Sweet's syndrome, or Sweet's panniculitis, is an uncommon variant of the classic syndrome, with hypodermal neutrophilic infiltration. The association of Sweet's syndrome with various malignancies has been reported. The most common underlying hematological malignancies are of myeloid origin; however, there have been several reports of the classic Sweet's syndrome in patients with a lymphoproliferative disorder, although the association of subcutaneous Sweet's syndrome with lymphoproliferative disorders has not been well-documented thus far. Herein, we present the case of a 48-year old man with a 2-year history of chronic lymphocytic leukemia who developed fever and skin rashes, without any evidence of a relapse. The clinical and pathological investigation resulted in the diagnosis of subcutaneous Sweet's syndrome. The patient exhibited no significant response to conventional therapeutic measures; however, following two subsequent doses of rituximab, his general condition and skin rash improved. The follow-up skin biopsy demonstrated dermal neutrophilic infiltrations in conjunction with prior mixed lobular and septal panniculitis, suggesting evolution of subcutaneous Sweet's syndrome to its classic form. To the best of our knowledge, this is one of the first reports of rituximab as a novel biological treatment for Sweet's syndrome. However, further randomized trials are required to evaluate the efficacy and safety of such biological therapies for Sweet's syndrome. PMID- 26998301 TI - Differences and correlation of serum CEA, CA19-9 and CA72-4 in gastric cancer. AB - The sensitivity of three biomarkers, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA72-4, in combination has been identified to be greater than that of any of the biomarkers considered in isolation in cases of gastric cancer (GC). However, the fundamental cause underlying this phenomenon remains to be fully elucidated. In the present study, the differences and correlation of these three biomarkers were investigated in patients with GC in order to determine how the three biomarkers in combination work more effectively compared with any of the biomarkers considered alone. The serum levels of CEA, CA19-9 and CA72-4 of 216 patients with gastric adenocarcinoma were analyzed on admission to hospital. The differences in positive rates and the serum levels of CEA, CA19-9 and CA72-4 were analyzed using the chi2 test and the non-parametric Wilcoxon two sample test. Phi (f) correlation analysis was used to study the correlation among the expression (positive or not) levels of CEA, CA19-9 and CA72-4. The correlation among the serum levels of biomarkers was analyzed using Spearman's test. The results demonstrated that the combined positive rate of CEA, CA19-9 and CA72-4 was significantly higher compared with the individual CEA, CA19-9 and CA72 4 positive rates (44.91% vs. 22.69, 18.98 and 22.69%, respectively; all P<0.05). The positive rate of CA19-9 and CA72-4 in the extent of the primary tumor/involvement of regional lymph node/distant metastases (TNM)-III/IV stage subgroup was higher compared with that in the TNM-I/II subgroup (chi2=5.902, P=0.015; chi2=8.009, P=0.005), although not the positive rate of CEA (chi2=0.302, P=0.583). A significant correlation was identified between the expression level of CEA and CA72-4 (f correlation coefficient=0.182; P=0.008) and between that of CA19-9 and CA72-4 (f correlation coefficient=0.189; P=0.006), although not between that of CEA and CA19-9 (f correlation coefficient=0.048; P=0.482) in the total number of patients with GC. A significant correlation was also identified between the serum levels of CEA and CA19-9, of CEA and CA72-4 and of CA19-9 and CA72-4 (Spearman's correlation coefficient=0.231, -0.271 and 0.167; P=0.001, P<0.0001 and P=0.014, respectively). The present study indicated that there was only a weak correlation between the positive rate of CEA and CA72-4 and between that of CA19-9 and CA72-4, and no correlation was identified between the positive rate of CEA and CA19-9, even if a correlation was identified between the serum levels of the biomarkers. The present study suggested that the evidence that the sensitivity of the three biomarkers in combination is greater than that of any of the biomarkers taken in isolation is due to less co-presentation of CEA, CA19-9 and CA72-4 in patients with GC. PMID- 26998303 TI - Non-traumatic acute paraplegia associated with a CT-guided needle biopsy in a silicotic nodule: A case report. AB - The present study reports the case of an adult patient with non-traumatic acute paraplegia following a computed tomography (CT)-guided automated cutting needle biopsy (ACNB). Multiple nodules and masses were revealed on performing chest radiography and CT on a 45-year-old man. In order to make a pathological diagnosis, a CT-guided biopsy using an automatic cutting needle was performed. However, 10 min after the biopsy, a weakness of the lower extremities occurred, and the patient collapsed to the ground, albeit with clear consciousness. Spinal magnetic resonance imaging (MRI) performed subsequently revealed no abnormal findings in the spinal cord. An MRI performed 24 h later, however, revealed swelling of the thoracic spinal cord and a high-signal-intensity lesion in T2 weighted images at the level of T7, T8 and T9. The patient subsequently received hyperbaric oxygen therapy for a few days, and rehabilitative treatment over the course of a few weeks. At 6 months following the biopsy, the patient was unable to walk, although the patient could stand for 10 min and defecate independently. Currently, the patient remains active in daily life, in spite of confinement to a wheelchair. The present case study was reported to raise the awareness of the possibility of spinal cord ischemia and acute paraplegia following a CT-guided ACNB of the lungs. The mechanism underlying spinal cord ischemia remains to be fully elucidated, although is thought to be multifactorial, involving air embolism. PMID- 26998302 TI - Sporadic colonic polyposis and adenocarcinoma associated with lymphoblastic and large B-cell lymphoma in a young male patient: A case report. AB - We herein report a case of colonic polyposis, colorectal carcinoma and large B cell lymphoma in a 22-year-old male patient with a previous history of childhood lymphoblastic lymphoma. Eight years after lymphoblastic lymphoma, which presented as mediastinal mass and superior vena cava syndrome, the patient complained of abdominal pain, lower gastrointestinal bleeding and an abdominal mass. The surgical exploration revealed numerous mucosal polyps throughout the large intestine, and multifocal masses in the ascending and transverse colon and the rectosigmoid region. A retroperitoneal mass was also found. The pathological examination revealed >100 tubular adenomatous polyps and a multifocal, well differentiated adenocarcinoma, with lymph node involvement and pericolic invasion. Interestingly, the immunohistochemical studies confirmed the malignant undifferentiated retroperitoneal mass as large B-cell lymphoma. Over a period of ~10 years, the patient had suffered from three different malignancies. To the best of our knowledge, such a combination of sporadic adenomatous colonic polyposis, colorectal carcinoma and two extra-intestinal non-Hodgkin lymphomas has not been reported to date. It should be considered that each malignancy increases the risk for other neoplastic diseases and a close follow-up is crucial for early detection of second malignancies and neoplastic syndromes. PMID- 26998304 TI - Totally implantable venous access port systems and associated complications: A single-institution retrospective analysis of 2,996 breast cancer patients. AB - Totally implantable venous access port systems (TIVAPS) are widely used in breast cancer patients. However, complications are frequent and may necessitate device replacement or removal, resulting in additional patient stress and treatment delays. The aim of this study was to investigate possible risk factors for complications. A total of 2,996 consecutive female breast cancer patients, with a median age of 50.2 years (range, 21.2-85.5 years) were enrolled in this observational, single-centre study between December, 2008 and April, 2014. TIVAPS implantation was principally performed using local anaesthesia and the blind puncture or Seldinger technique through internal jugular or subclavian vein access. A retrospective chart review was conducted to obtain information associated with TIVAPS and patient data. Insertion performed by blind puncture and Seldinger technique had a success ratio of 96.34 and 99.80%, respectively (chi2=29.905, P<0.001). However, the success ratio of the puncture technique group was 99.76% when the TIVAPS was implanted in the right internal jugular vein. The most common complications were late complications, with an overall incidence rate of 5.41% (162/2,996) during the entire device duration. The most common late complications included fibrin formation (1.84%, 55/2,996), port related bacteraemia (1.44%, 43/2,996) and deep vein thrombosis (0.63%, 19/2,996). No patient died during the study. Our results demonstrated that insertion of TIVAPS by blind puncture or the Seldinger technique through internal jugular or subclavian vein access is convenient, and insertion by the Seldinger technique through the right internal jugular vein is the preferred method. Therefore, TIVAPS is safe for continuous infusional chemotherapy regimens for breast cancer patients. PMID- 26998305 TI - A rare presentation of a large goiter with papillary thyroid microcarcinoma as a chest wall mass: A case report. AB - Nodular goiter affects numerous individuals worldwide. As the thyroid enlarges, it normally extends into the mediastinum as a result of its anatomical location under the investing layer of the deep cervical fascia. The present study reports the rare case of a 76-year-old man who suffered from a goiter with papillary thyroid microcarcinoma, who presented as a subcutaneous partially cystic with solid areas lesion over the chest. The patient underwent surgery and on histopathological examination, the predominant mass was characterized as a multinodular goiter with hemorrhage, necrosis and cystic change. A papillary thyroid microcarcinoma with a diameter of 0.2 cm was identified. The present study demonstrated a rare, to the best of our knowledge, presentation of a benign multinodular goiter in this way. PMID- 26998306 TI - Socio-cultural context of eating disorders in Poland. AB - BACKGROUND: The goal of this study was to assess the relationship between sociocultural factors and clinical eating disorders during the intensive process of Westernisation in Poland that occurred after 1989. The study population included girls diagnosed with an eating disorder according to DSM-IV criteria (n = 47 anorexia nervosa restrictive type [ANR], n = 16 anorexia binge/purge type [ANBP], n = 34 bulimia nervosa [BN], n = 19 eating disorder not otherwise specified [EDNOS]) who received consultation for the first time between 2002 and 2004 in the Department of Clinical Child and Adolescent Psychiatry, University Hospital, Krakow, Poland. The study included an age-matched normal control group [NOR] of 85 schoolgirls from Krakow. METHODS: Relationships between two given qualitative features were investigated using the chi-square test or Fisher's exact test. Correspondence analysis was applied to graphically explore the relationship. The Kruskal-Wallis test with the Bonferroni was performed to compare quantitative results across groups. RESULTS: Objective sociodemographic variables and responses to the 62-item Questionnaire of Socio-cultural Context were measured. The mothers of ANBP and BN patients were less professionally active than mothers of ANR patients and NOR subjects. Subjective socio-cultural factors were more relevant for the BN group than the ANR group. Questionnaire responses in the ANBP group were more similar to those in the BN group than to those in the ANR group. The most unambiguous and specific characteristic of the ANR group was a sense of belonging to the middle class. Variables that differentiated the BN group from the NOR group included the importance attached to thinness treated as an expression of power and control over one's self, as well as a multifaceted negative evaluation of one's own family, including a negative assessment of the position of women and parental lack of concern for appearance and principles of nutrition. All patients, regardless of diagnosis, identified with other people with similar problems and considered anorexia and bulimia to be a major issue of their generation and social environment. CONCLUSIONS: The results of this first in Poland exploratory study of socio cultural context of eating disorders indicate the importance of both objective and subjective socio-cultural factors in eating disorders in the group studied. PMID- 26998308 TI - A case of multiple myeloma presenting as a distal renal tubular acidosis with extensive bilateral nephrolithiasis. AB - BACKGROUND: At the time of diagnosis, Multiple Myeloma is commonly associated with renal impairment. Renal tubular acidosis without overt renal insufficiency is an uncommon disease presentation of myeloma. Among tubular acidosis types, isolated renal tubular acidosis is a very unusual presentation of multiple myeloma. CASE PRESENTATION: We present a 55 years old female who presented with lower limb weakness due to persistent hypokalaemia caused by distal renal tubular acidosis. On further investigation of her anaemia with high erythrocyte sedimentation rate, we diagnosed IgG myeloma. CONCLUSION: Isolated distal renal tubular acidosis is a rare presentation of multiple myeloma. In the absence of hypercalciuria and demonstrable light chain excretion in urine, we assumed that the distal renal tubular acidosis could have been caused by monoclonal hypergammaglobulinaemic state of multiple myeloma. PMID- 26998307 TI - Silica Nanoparticle-Generated ROS as a Predictor of Cellular Toxicity: Mechanistic Insights and Safety by Design. AB - Evaluating toxicological responses of engineered nanomaterials such as silica nanoparticles is critical in assessing health risks and exposure limits. Biological assays can be used to evaluate cytotoxicity of individual materials, but specific nano-bio interactions-which govern its physiological response-cannot currently be predicted from materials characterization and physicochemical properties. Understanding the role of free radical generation from nanomaterial surfaces facilitates understanding of a potential toxicity mechanism and provides insight into how toxic effects can be assessed. Size-matched mesoporous and nonporous silica nanoparticles in aminopropyl-functionalized and native forms were investigated to analyze the effects of porosity and surface functionalization on the observed cytotoxicity. In vitro cell viability data in a murine macrophage cell line (RAW 264.7) provides a model for what might be observed in terms of cellular toxicity upon an environmental or industrial exposure to silica nanoparticles. Electron paramagnetic resonance spectroscopy was implemented to study free radical species generated from the surface of these nanomaterials and the signal intensity was correlated with cellular toxicity. In addition, in vitro assay of intracellular reactive oxygen species (ROS) matched well with both the EPR and cell viability data. Overall, spectroscopic and in vitro studies correlate well and implicate production of ROS from a surface catalyzed reaction as a predictor of cellular toxicity. The data demonstrate that mesoporous materials are intrinsically less toxic than nonporous materials, and that surface functionalization can mitigate toxicity in nonporous materials by reducing free radical production. The broader implications are in terms of safety by design of nanomaterials, which can only be extracted by mechanistic studies such as the ones reported here. PMID- 26998309 TI - Volume and Value of Big Healthcare Data. AB - Modern scientific inquiries require significant data-driven evidence and trans disciplinary expertise to extract valuable information and gain actionable knowledge about natural processes. Effective evidence-based decisions require collection, processing and interpretation of vast amounts of complex data. The Moore's and Kryder's laws of exponential increase of computational power and information storage, respectively, dictate the need rapid trans-disciplinary advances, technological innovation and effective mechanisms for managing and interrogating Big Healthcare Data. In this article, we review important aspects of Big Data analytics and discuss important questions like: What are the challenges and opportunities associated with this biomedical, social, and healthcare data avalanche? Are there innovative statistical computing strategies to represent, model, analyze and interpret Big heterogeneous data? We present the foundation of a new compressive big data analytics (CBDA) framework for representation, modeling and inference of large, complex and heterogeneous datasets. Finally, we consider specific directions likely to impact the process of extracting information from Big healthcare data, translating that information to knowledge, and deriving appropriate actions. PMID- 26998311 TI - Predicting chemoinsensitivity in breast cancer with 'omics/digital pathology data fusion. AB - Predicting response to treatment and disease-specific deaths are key tasks in cancer research yet there is a lack of methodologies to achieve these. Large scale 'omics and digital pathology technologies have led to the need for effective statistical methods for data fusion to extract the most useful patterns from these diverse data types. We present FusionGP, a method for combining heterogeneous data types designed specifically for predicting outcome of treatment and disease. FusionGP is a Gaussian process model that includes a generalization of feature selection for biomarker discovery, allowing for simultaneous, sparse feature selection across multiple data types. Importantly, it can accommodate highly nonlinear structure in the data, and automatically infers the optimal contribution from each input data type. FusionGP compares favourably to several popular classification methods, including the Random Forest classifier, a stepwise logistic regression model and the Support Vector Machine on single data types. By combining gene expression, copy number alteration and digital pathology image data in 119 estrogen receptor (ER)-negative and 345 ER positive breast tumours, we aim to predict two important clinical outcomes: death and chemoinsensitivity. While gene expression data give the best predictive performance in the majority of cases, the digital pathology data are much better for predicting death in ER cases. Thus, FusionGP is a new tool for selecting informative features from heterogeneous data types and predicting treatment response and prognosis. PMID- 26998312 TI - Big data integration shows Australian bush-fire frequency is increasing significantly. AB - Increasing Australian bush-fire frequencies over the last decade has indicated a major climatic change in coming future. Understanding such climatic change for Australian bush-fire is limited and there is an urgent need of scientific research, which is capable enough to contribute to Australian society. Frequency of bush-fire carries information on spatial, temporal and climatic aspects of bush-fire events and provides contextual information to model various climate data for accurately predicting future bush-fire hot spots. In this study, we develop an ensemble method based on a two-layered machine learning model to establish relationship between fire incidence and climatic data. In a 336 week data trial, we demonstrate that the model provides highly accurate bush-fire incidence hot-spot estimation (91% global accuracy) from the weekly climatic surfaces. Our analysis also indicates that Australian weekly bush-fire frequencies increased by 40% over the last 5 years, particularly during summer months, implicating a serious climatic shift. PMID- 26998310 TI - Parental attitudes to genetic testing differ by ethnicity and immigration in childhood nephrotic syndrome: a cross-sectional study. AB - BACKGROUND: Studies in the USA report differences in opinion among parents of different ethnic groups toward genetic testing for their child; however, there are no studies that address this issue in the diverse ethnic and immigrant population in Canada. OBJECTIVE: This study aims to determine whether ethnicity and immigration status influences parental interest in clinical genetic testing for a potentially progressive kidney disease. DESIGN: This is a cross-sectional study. SETTING: Participants were recruited from the Greater Toronto Area, Canada. PARTICIPANTS: The study included 320 parents of children ages 1-18 years with nephrotic syndrome enrolled in the Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT) observational cohort study. MEASUREMENTS: Demographic, ethnicity, immigration, and child specific factors as well as interest in genetic testing were collected through self reported questionnaires administered at baseline study visit. METHODS: Logistic regression models were used to examine association of ethnicity and immigration status with interest in genetic testing. RESULTS: The majority of parents (85 %) were interested in genetic testing for their child. South Asian and East/Southeast Asian parents had 74 and 76 % lower odds of agreeing to genetic testing when compared to Europeans (odds ratio (OR) 0.26, 95 % confidence interval (CI) 0.10-0.68; OR 0.24, 95 % CI 0.07-0.79, respectively) after controlling for age and sex of child, age and education level of parent, initial steroid resistance, and duration of time in Canada. Immigrants to Canada also had significantly lower odds (OR 0.29, 95 % CI 0.12-0.72) of agreeing to genetic testing after similar adjustment. Higher education level was not associated with greater interest in genetic testing (OR 1.24, 95 % CI 0.64-2.42). LIMITATIONS: Participants have already agreed to aggregate genetic testing for research purposes as part of enrolment in INSIGHT study. CONCLUSION: While majority of parents were interested in genetic testing for their child, immigrants, particularly South Asians and East/Southeast Asians, were more likely to decline genetic testing. Genetic counseling needs to be tailored to address specific concerns in these parental groups to maximize informed decision-making in the clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01605266. PMID- 26998313 TI - Comparing maternal genetic variation across two millennia reveals the demographic history of an ancient human population in southwest Turkey. AB - More than two decades of archaeological research at the site of Sagalassos, in southwest Turkey, resulted in the study of the former urban settlement in all its features. Originally settled in late Classical/early Hellenistic times, possibly from the later fifth century BCE onwards, the city of Sagalassos and its surrounding territory saw empires come and go. The Plague of Justinian in the sixth century CE, which is considered to have caused the death of up to a third of the population in Anatolia, and an earthquake in the seventh century CE, which is attested to have devastated many monuments in the city, may have severely affected the contemporary Sagalassos community. Human occupation continued, however, and Byzantine Sagalassos was eventually abandoned around 1200 CE. In order to investigate whether these historical events resulted in demographic changes across time, we compared the mitochondrial DNA variation of two population samples from Sagalassos (Roman and Middle Byzantine) and a modern sample from the nearby town of Aglasun. Our analyses revealed no genetic discontinuity across two millennia in the region and Bayesian coalescence-based simulations indicated that a major population decline in the area coincided with the final abandonment of Sagalassos, rather than with the Plague of Justinian or the mentioned earthquake. PMID- 26998314 TI - Are there statistical links between the direction of European weather systems and ENSO, the solar cycle or stratospheric aerosols? AB - The Hess Brezowsky Grobetawetterlagen (HBGWL) European weather classification system, accumulated over a long period (more than 130 years), provides a rare opportunity to examine the impact of various factors on regional atmospheric flow. We have used these data to examine changes in the frequency (days/month) of given weather systems direction (WSD) during peak phases in the North Atlantic Oscillation (NAO), El Nino Southern Oscillation (ENSO), solar cycle (SC) and peaks in stratospheric aerosol optical depth (AOD) with superposed epoch analysis and Monte Carlo significance testing. We found highly significant responses to the NAO consistent with expectations: this signal confirmed the utility of the HBGWL data for this type of analysis and provided a benchmark of a clear response. WSD changes associated with ENSO, SC and AOD were generally within the ranges expected from random samples. When seasonal restrictions were added the results were similar, however, we found one clearly significant result: an increase in southerly flow of 2.6+/-0.8 days/month (p=1.9*10(-4)) during boreal summertime in association with El Nino. This result supports the existence of a robust teleconnection between the ENSO and European weather. PMID- 26998315 TI - High atmospheric temperatures and 'ambient incubation' drive embryonic development and lead to earlier hatching in a passerine bird. AB - Tropical and subtropical species typically experience relatively high atmospheric temperatures during reproduction, and are subject to climate-related challenges that are largely unexplored, relative to more extensive work conducted in temperate regions. We studied the effects of high atmospheric and nest temperatures during reproduction in the zebra finch. We characterized the temperature within nests in a subtropical population of this species in relation to atmospheric temperature. Temperatures within nests frequently exceeded the level at which embryo's develop optimally, even in the absence of parental incubation. We experimentally manipulated internal nest temperature to demonstrate that an average difference of 6 degrees C in the nest temperature during the laying period reduced hatching time by an average of 3% of the total incubation time, owing to 'ambient incubation'. Given the avian constraint of laying a single egg per day, the first eggs of a clutch are subject to prolonged effects of nest temperature relative to later laid eggs, potentially increasing hatching asynchrony. While birds may ameliorate the negative effects of ambient incubation on embryonic development by varying the location and design of their nests, high atmospheric temperatures are likely to constitute an important selective force on avian reproductive behaviour and physiology in subtropical and tropical regions, particularly in the light of predicted climate change that in many areas is leading to a higher frequency of hot days during the periods when birds breed. PMID- 26998316 TI - Thermodynamics and kinetics of the FoF1-ATPase: application of the probability isotherm. AB - We use the results of recent publications as vehicles with which to discuss the thermodynamics of the proton-driven mitochondrial F o F1-ATP synthase, focusing particularly on the possibility that there may be dissociation between rotatory steps and ATP synthesis/hydrolysis. Such stoichiometric 'slippage' has been invoked in the literature to explain observed non-ideal behaviour. Numerical solution of the Rate Isotherm (the kinetic equivalent of the more fundamental Probability Isotherm) suggests that such 'slippage' is an unlikely explanation; instead, we suggest that the experimental results may be more consistent with damage to the enzyme caused by its isolation from the biomembrane and its experimental fixation, resulting in non-physiological friction within the enzyme's rotary mechanism. We emphasize the unavoidable constraint of the Second Law as instantiated by the obligatory dissipation of Gibbs Free Energy if the synthase is to operate at anything other than thermodynamic equilibrium. We use further numerical solution of the Rate Isotherm to demonstrate that there is no necessary association of low thermodynamic efficiency with high metabolic rates in a bio-world in which the dominating mechanism of metabolic control is multifactorial enzyme activation. PMID- 26998317 TI - Simulated annealing approach to vascular structure with application to the coronary arteries. AB - Do the complex processes of angiogenesis during organism development ultimately lead to a near optimal coronary vasculature in the organs of adult mammals? We examine this hypothesis using a powerful and universal method, built on physical and physiological principles, for the determination of globally energetically optimal arterial trees. The method is based on simulated annealing, and can be used to examine arteries in hollow organs with arbitrary tissue geometries. We demonstrate that the approach can generate in silico vasculatures which closely match porcine anatomical data for the coronary arteries on all length scales, and that the optimized arterial trees improve systematically as computational time increases. The method presented here is general, and could in principle be used to examine the arteries of other organs. Potential applications include improvement of medical imaging analysis and the design of vascular trees for artificial organs. PMID- 26998319 TI - Parental investment in child health in sub-Saharan Africa: a cross-national study of health-seeking behaviour. AB - Parents face trade-offs between investing in child health and other fitness enhancing activities. In humans, parental investment theory has mostly been examined through the analysis of differential child outcomes, with less emphasis on the actions parents take to further a particular offspring's condition. Here, we make use of household data on health-seeking for children in a high mortality context where such behaviours are crucial for offspring survival. Using Demographic and Health Survey (DHS) data from 17 sub-Saharan African countries, we examine whether maternal factors (age, health, marital status) and child factors (birth order, health, sex, age) independently influence parental investment in health-seeking behaviours: two preventative behaviours (malaria net use and immunization) and two curative ones (treating fever and diarrhoea). Results indicate that children with lower birth order, older mothers and mothers with better health status have higher odds of investment. The effects of a child's sex and health status and whether the mother is polygynously married vary depending on the type of health-seeking behaviour (preventative versus curative). We discuss how these results square with predictions from parental investment theory pertaining to the state of mothers and children, and reflect on some potential mechanisms and directions for future research. PMID- 26998318 TI - She more than he: gender bias supports the empathic nature of yawn contagion in Homo sapiens. AB - Psychological, clinical and neurobiological findings endorse that empathic abilities are more developed in women than in men. Because there is growing evidence that yawn contagion is an empathy-based phenomenon, we expect that the female bias in the empathic abilities reflects on a gender skew in the responsiveness to others' yawns. We verified this assumption by applying a linear model on a dataset gathered during a 5 year period of naturalistic observations on humans. Gender, age and social bond were included in the analysis as fixed factors. The social bond and the receiver's gender remained in the best model. The rates of contagion were significantly lower between acquaintances than between friends and family members, and significantly higher in women than in men. These results not only confirm that yawn contagion is sensitive to social closeness, but also that the phenomenon is affected by the same gender bias affecting empathy. The sex skew, also found in other non-human species, fits with the female social roles which are likely to require higher empathic abilities (e.g. parental care, group cohesion maintenance, social mediation). The fact that female influence in social dynamics also relies on face-to-face emotional exchange raises concerns on the negative repercussions of having women's facial expressions forcibly concealed. PMID- 26998320 TI - The eastern migratory caribou: the role of genetic introgression in ecotype evolution. AB - Understanding the evolutionary history of contemporary animal groups is essential for conservation and management of endangered species like caribou (Rangifer tarandus). In central Canada, the ranges of two caribou subspecies (barren ground/woodland caribou) and two woodland caribou ecotypes (boreal/eastern migratory) overlap. Our objectives were to reconstruct the evolutionary history of the eastern migratory ecotype and to assess the potential role of introgression in ecotype evolution. STRUCTURE analyses identified five higher order groups (i.e. three boreal caribou populations, eastern migratory ecotype and barren-ground). The evolutionary history of the eastern migratory ecotype was best explained by an early genetic introgression from barren-ground into a woodland caribou lineage during the Late Pleistocene and subsequent divergence of the eastern migratory ecotype during the Holocene. These results are consistent with the retreat of the Laurentide ice sheet and the colonization of the Hudson Bay coastal areas subsequent to the establishment of forest tundra vegetation approximately 7000 years ago. This historical reconstruction of the eastern migratory ecotype further supports its current classification as a conservation unit, specifically a Designatable Unit, under Canada's Species at Risk Act. These findings have implications for other sub-specific contact zones for caribou and other North American species in conservation unit delineation. PMID- 26998321 TI - A highly infective plant-associated bacterium influences reproductive rates in pea aphids. AB - Pea aphids, Acyrthosiphon pisum, have the potential to increase reproduction as a defence against pathogens, though how frequently this occurs or how infection with live pathogens influences this response is not well understood. Here we determine the minimum infective dose of an environmentally common bacterium and possible aphid pathogen, Pseudomonas syringae, to determine the likelihood of pathogenic effects to pea aphids. Additionally, we used P. syringae infection to investigate how live pathogens may alter reproductive rates. We found that oral bacterial exposure decreased subsequent survival of aphids in a dose-dependent manner and we estimate that ingestion of less than 10 bacterial cells is sufficient to increase aphid mortality. Pathogen dose was positively related to aphid reproduction. Aphids exposed to low bacterial doses showed decreased, although statistically indistinguishable, fecundity compared to controls. Aphids exposed to high doses reproduced significantly more than low dose treatments and also more, but not significantly so, than controls. These results are consistent with previous studies suggesting that pea aphids may use fecundity compensation as a response to pathogens. Consequently, even low levels of exposure to a common plant-associated bacterium may therefore have significant effects on pea aphid survival and reproduction. PMID- 26998322 TI - A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis. AB - Genes controlling muscle size and survival play important roles in muscle wasting diseases. In Drosophila melanogaster metamorphosis, larval abdominal muscles undergo two developmental fates. While a doomed population is eliminated by cell death, another persistent group is remodelled and survives into adulthood. To identify and characterize genes involved in the development of remodelled muscles, we devised a workflow consisting of in vivo imaging, targeted gene perturbation and quantitative image analysis. We show that inhibition of TOR signalling and activation of autophagy promote developmental muscle atrophy in early, while TOR and yorkie activation are required for muscle growth in late pupation. We discovered changes in the localization of myonuclei during remodelling that involve anti-polar migration leading to central clustering followed by polar migration resulting in localization along the midline. We demonstrate that the Cathepsin L orthologue Cp1 is required for myonuclear clustering in mid, while autophagy contributes to central positioning of nuclei in late metamorphosis. In conclusion, studying muscle remodelling in metamorphosis can provide new insights into the cell biology of muscle wasting. PMID- 26998323 TI - Comparison of social structures within cities of very different sizes. AB - People make a city, making each city as unique as the combination of its inhabitants. However, some cities are similar and some cities are inimitable. We examine the social structure of 10 different cities using Twitter data. Each city is decomposed to its communities. We show that in many cases one city can be thought of as an amalgamation of communities from another city. For example, we find the social network of Manchester is very similar to the social network of a virtual city of the same size, where the virtual city is composed of communities from the Bristol network. However, we cannot create Bristol from Manchester since Bristol contains communities with a social structure that are not present in Manchester. Some cities, such as Leeds, are outliers. That is, Leeds contains a particularly wide range of communities, meaning we cannot build a similar city from communities outside of Leeds. Comparing communities from different cities, and building virtual cities that are comparable to real cities, is a novel approach to understand social networks. This has implications when using social media to inform or advise residents of a city. PMID- 26998324 TI - Predator olfactory cues generate a foraging-predation trade-off through prey apprehension. AB - Most animals are faced with the challenge of securing food under the risk of predation. This frequently generates a trade-off whereby animals respond to predator cues with reduced movement to avoid predation at the direct cost of reduced foraging success. However, predators may also cause prey to be apprehensive in their foraging activities, which would generate an indirect 'apprehension cost'. Apprehension arises when a forager redirects attention from foraging tasks to predator detection and incurs a cost from such multi-tasking, because the forager ends up making more mistakes in its foraging tasks as a result. Here, we test this apprehension cost hypothesis and show that damselflies miss a greater proportion of their prey during foraging bouts in response to both olfactory cues produced by conspecifics that have only viewed a fish predator and olfactory cues produced directly by fish. This reduced feeding efficiency is in addition to the stereotypical anti-predator response of reduced activity, which we also observed. These results show that costs associated with anti-predator responses not only arise through behavioural alterations that reduce the risk of predation, but also from the indirect costs of apprehension and multi-tasking that can reduce feeding efficiency under the threat of predation. PMID- 26998325 TI - Random noise can help to improve synchronization of excimer laser pulses. AB - Recently, we have reported on a compact microcontroller-based unit developed to accurately synchronize excimer laser pulses (Mingesz et al. 2012 Fluct. Noise Lett. 11, 1240007 (doi:10.1142/S021947751240007X)). We have shown that dithering based on random jitter noise plus pseudorandom numbers can be used in the digital control system to radically reduce the long-term drift of the laser pulse from the trigger and to improve the accuracy of the synchronization. In this update paper, we present our new experimental results obtained by the use of the delay controller unit to tune the timing of a KrF excimer laser as an addition to our previous numerical simulation results. The hardware was interfaced to the laser using optical signal paths in order to reduce sensitivity to electromagnetic interference and the control algorithm tested by simulations was applied in the experiments. We have found that the system is able to reduce the delay uncertainty very close to the theoretical limit and performs well in real applications. The simple, compact and flexible system is universal enough to also be used in various multidisciplinary applications. PMID- 26998326 TI - Post-main-sequence planetary system evolution. AB - The fates of planetary systems provide unassailable insights into their formation and represent rich cross-disciplinary dynamical laboratories. Mounting observations of post-main-sequence planetary systems necessitate a complementary level of theoretical scrutiny. Here, I review the diverse dynamical processes which affect planets, asteroids, comets and pebbles as their parent stars evolve into giant branch, white dwarf and neutron stars. This reference provides a foundation for the interpretation and modelling of currently known systems and upcoming discoveries. PMID- 26998327 TI - Dopamine regulates termite soldier differentiation through trophallactic behaviours. AB - Caste polyphenism in social insects is regulated by social interactions among colony members. Trophallaxis is one of the most frequently observed interactions, but no studies have been conducted identifying the intrinsic factors involved in this behaviour and caste differentiation. Dopamine (DA) has multiple roles in the modulation of behaviours and physiology, and it produces species-specific behaviours in animals. Here, to verify the role of DA in termite soldier differentiation, we focused on the first soldier in an incipient colony of Zootermopsis nevadensis, which always differentiates from the oldest 3rd instar (No. 1 larva) via a presoldier. First, brain DA levels of the No. 1 larva at day 3 after its appearance were significantly higher than day 0. Second, DA synthesis gene expression levels were extraordinarily high in the No. 1 larva at day 0-1 after appearance. Finally, injection of a DA receptor antagonist into the No. 1 larva resulted in the inhibition of presoldier differentiation. Behavioural observations of the antagonist or control-injected larvae suggested that brain DA and signalling activity regulate the frequencies of trophallaxis from reproductives and presoldier differentiation. Because trophallaxis is a social behaviour frequently observed in natural conditions, the role of DA should be investigated in other social insects with frequent trophallactic and allogrooming behaviour. PMID- 26998328 TI - Computational exploration of the reaction mechanism of the Cu(+)-catalysed synthesis of indoles from N-aryl enaminones. AB - We have studied the role of Cu(+)-phenantroline as a catalyst in the cyclization of N-aryl-enaminones using density-functional theory computations. The catalyst was found to bind the substrate upon deprotonation of its eneaminone, and to dramatically increase the acidity of the carbon adjacent to the ketone functionality. The deprotonation of this carbon atom yields a carbanion which attacks the aryl moiety, thereby closing the heterocycle in the rate-determining step. This C-C bond forming reaction was found to proceed much more rapidly when preceded by re-protonation of the substrate N-atom (which had lost H(+) in the initial step). Hydride transfer to the catalyst then completes the indole synthesis, in a very fast step. The influence of Li(+) and K(+) on the regio selectivity of the cyclization of bromo-substituted analogues could not, however, be reproduced by our model. Alternative pathways involving either single-electron transfer from the catalyst to the substrate or ring cyclization without previous carbon alpha-deprotonation were found to be kinetically or thermodynamically inaccessible. PMID- 26998329 TI - An individual-based forest model links canopy dynamics and shade tolerances along a soil moisture gradient. AB - Understanding how forested ecosystems respond to climatic changes is a challenging problem as forest self-organization occurs simultaneously across multiple scales. Here, we explore the hypothesis that soil water availability shapes above-ground competition and gap dynamics, and ultimately alters the dominance of shade tolerant and intolerant species along the moisture gradient. We adapt a spatially explicit individual-based model with simultaneous crown and root competitions. Simulations show that the transition from xeric to mesic soils is accompanied by an increase in shade-tolerant species similar to the patterns documented in the North American forests. This transition is accompanied by a change from water to sunlight competitions, and happens at three successive stages: (i) mostly water-limited parkland, (ii) simultaneously water- and sunlight-limited closed canopy forests featuring a very sparse understory, and (iii) mostly sunlight-limited forests with a populated understory. This pattern is caused by contrasting successional dynamics that favour either shade-tolerant or shade-intolerant species, depending on soil moisture and understory density. This work demonstrates that forest patterns along environmental gradients can emerge from spatial competition without physiological trade-offs between shade and growth tolerance. Mechanistic understanding of population processes involved in the forest-parkland-desert transition will improve our ability to explain species distributions and predict forest responses to climatic changes. PMID- 26998330 TI - Functional cervicothoracic boundary modified by anatomical shifts in the neck of giraffes. AB - Here we examined the kinematic function of the morpho- logically unique first thoracic vertebra in giraffes. The first thoracic vertebra of the giraffe displayed similar shape to the seventh cervical vertebra in general ruminants. The flexion experiment using giraffe carcasses demonstrated that the first thoracic vertebra exhibited a higher dorsoventral mobility than other thoracic vertebrae. Despite the presence of costovertebral joints, restriction in the intervertebral movement imposed by ribs is minimized around the first thoracic vertebra by subtle changes of the articular system between the vertebra and ribs. The attachment area of musculus longus colli, mainly responsible for ventral flexion of the neck, is partly shifted posteriorly in the giraffe so that the force generated by muscles is exerted on the cervical vertebrae and on the first thoracic vertebra. These anatomical modifications allow the first thoracic vertebra to adopt the kinematic function of a cervical vertebra in giraffes. The novel movable articulation in the thorax functions as a fulcrum of neck movement and results in a large displacement of reachable space in the cranial end of the neck. The unique first thoracic vertebra in giraffes provides higher flexibility to the neck and may provide advantages for high browsing and/or male competition behaviours specific to giraffes. PMID- 26998331 TI - Spatial variation in risk and consequence of Batrachochytrium salamandrivorans introduction in the USA. AB - A newly identified fungal pathogen, Batrachochytrium salamandrivorans(Bsal), is responsible for mass mortality events and severe population declines in European salamanders. The eastern USA has the highest diversity of salamanders in the world and the introduction of this pathogen is likely to be devastating. Although data are inevitably limited for new pathogens, disease-risk assessments use best available data to inform management decisions. Using characteristics of Bsalecology, spatial data on imports and pet trade establishments, and salamander species diversity, we identify high-risk areas with both a high likelihood of introduction and severe consequences for local salamanders. We predict that the Pacific coast, southern Appalachian Mountains and mid-Atlantic regions will have the highest relative risk from Bsal. Management of invasive pathogens becomes difficult once they are established in wildlife populations; therefore, import restrictions to limit pathogen introduction and early detection through surveillance of high-risk areas are priorities for preventing the next crisis for North American salamanders. PMID- 26998332 TI - Morphological adaptation of the calamistrum to the cribellate spinning process in Deinopoidae (Uloboridae, Deinopidae). AB - Spiders are famous for their silk with fascinating mechanical properties. However, some can further produce, process and handle nano fibres, which are used as capture threads. These 'cribellate spiders' bear a specialized setae comb on their metatarsus (calamistrum), which modifies cribellate nano fibres to assemble a puffy structure within the capture thread. Among different species, the calamistrum morphology can differ remarkably. Although a model of thread production has been established for Uloborus plumipes, it is not resolved if/how different shaped calamistra influence the production process. We were able to transfer the model without restrictions to spiders with different shaped calamistra. Fibres are not locked between setae but are passing across a rather smooth surface-like area on the calamistrum. This area can be relocated, explaining the first morphological difference between calamistra, without changing the influence of the calamistrum on fibres. By performing an elongated leg movement, contact between fibres and calamistrum could be adjusted after finishing thread production. This movement has to bring the thread in contact with the second morphological peculiarity: cribellate teeth. We suggest these teeth are used to handle the thread independently of the spinnerets, a feature only necessary for spiders, which do not move during web construction. PMID- 26998333 TI - Kinship as a frequency dependent strategy. AB - Humans divide themselves up into separate cultures, which is a unique and ubiquitous characteristic of our species. Kinship norms are one of the defining features of such societies. Here we show how norms of marital residence can evolve as a frequency-dependent strategy, using real-world cases from southwestern China and an evolutionary game model. The process of kinship change has occurred in the past and is also occurring now in southwestern China. Our data and models show how transitions between residence types can occur both as response to changing costs and benefits of co-residence with kin, and also due to the initial frequency of the strategies adopted by others in the population: patrilocal societies can become matrilocal, and neolocal societies can become duolocal. This illustrates how frequency-dependent selection plays a role both in the maintenance of group-level cultural diversity and in cultural extinction. PMID- 26998334 TI - Does influenza A virus infection affect movement behaviour during stopover in its wild reservoir host? AB - The last decade has seen a surge in research on avian influenza A viruses (IAVs), in part fuelled by the emergence, spread and potential zoonotic importance of highly pathogenic virus subtypes. The mallard (Anas platyrhynchos) is the most numerous and widespread dabbling duck in the world, and one of the most important natural hosts for studying IAV transmission dynamics. In order to predict the likelihood of IAV transmission between individual ducks and to other hosts, as well as between geographical regions, it is important to understand how IAV infection affects the host. In this study, we analysed the movements of 40 mallards equipped with GPS transmitters and three-dimensional accelerometers, of which 20 were naturally infected with low pathogenic avian influenza virus (LPAIV), at a major stopover site in the Northwest European flyway. Movements differed substantially between day and night, as well as between mallards returning to the capture site and those feeding in natural habitats. However, movement patterns did not differ between LPAIV infected and uninfected birds. Hence, LPAIV infection probably does not affect mallard movements during stopover, with high possibility of virus spread along the migration route as a consequence. PMID- 26998335 TI - The unexpected survival of an ancient lineage of anseriform birds into the Neogene of Australia: the youngest record of Presbyornithidae. AB - Presbyornithids were the dominant birds in Palaeogene lacustrine assemblages, especially in the Northern Hemisphere, but are thought to have disappeared worldwide by the mid-Eocene. Now classified within Anseriformes (screamers, ducks, swans and geese), their relationships have long been obscured by their strange wader-like skeletal morphology. Reassessment of the late Oligocene South Australian material attributed to Wilaru tedfordi, long considered to be of a stone-curlew (Burhinidae, Charadriiformes), reveals that this taxon represents the first record of a presbyornithid in Australia. We also describe the larger Wilaru prideauxi sp. nov. from the early Miocene of South Australia, showing that presbyornithids survived in Australia at least until ca 22 Ma. Unlike on other continents, where presbyornithids were replaced by aquatic crown-group anatids (ducks, swans and geese), species of Wilaru lived alongside these waterfowl in Australia. The morphology of the tarsometatarsus of these species indicates that, contrary to other presbyornithids, they were predominantly terrestrial birds, which probably contributed to their long-term survival in Australia. The morphological similarity between species of Wilaru and the Eocene South American presbyornithid Telmabates antiquus supports our hypothesis of a Gondwanan radiation during the evolutionary history of the Presbyornithidae. Teviornis gobiensis from the Late Cretaceous of Mongolia is here also reassessed and confirmed as a presbyornithid. These findings underscore the temporal continuance of Australia's vertebrates and provide a new context in which the phylogeny and evolutionary history of presbyornithids can be examined. PMID- 26998336 TI - Social familiarity affects Diana monkey (Cercopithecus diana diana) alarm call responses in habitat-specific ways. AB - Male Diana monkeys produce loud and acoustically distinct alarm calls to leopards and eagles that propagate over long distances, much beyond the immediate group. Calling is often contagious, with neighbouring males responding to each other's calls, indicating that harem males communicate both to local group members and distant competitors. Here, we tested whether male Diana monkeys responding to each other's alarm calls discriminated familiar from unfamiliar callers in two populations in Tai Forest (Ivory Coast) and on Tiwai Island (Sierra Leone). At both sites, we found specific acoustic markers in male alarm call responses that discriminated familiar from unfamiliar callers, but response patterns were site specific. On Tiwai Island, males responded to familiar males' eagle alarms with 'standard' eagle alarm calls, whereas unfamiliar males triggered acoustically atypical eagle alarms. The opposite was found in Tai Forest where males responded to unfamiliar males' eagle alarm calls with 'standard' eagle alarms, and with atypical eagle alarms to familiar males' calls. Moreover, only Tai, but not Tiwai, males also marked familiarity with the caller in their leopard-induced alarms. We concluded that male Diana monkeys encode not only predator type but also signaller familiarity in their alarm calls, although in population-specific ways. We explain these inter-site differences in vocal behaviour in terms of differences in predation pressure and population density. We discuss the adaptive function and implications of this behaviour for the origins of acoustic flexibility in primate communication. PMID- 26998337 TI - Short- and long-term consequences of developmental saline stress: impacts on anuran respiration and behaviour. AB - Secondary salinization has been identified as a major stressor to amphibians. Exposure to elevated salinity necessitates physiological adjustments and biochemical changes that may be energetically demanding. As such, exposure to non lethal levels of salinity during development could potentially alter anuran metabolic rates and individual performance in both pre- and post-metamorphic life stages. We investigated the effects of non-lethal levels of salinity on metamorphic traits (time to reach metamorphosis and metamorphic mass), tadpole oxygen consumption, escape response behaviour (pre- and post-metamorphosis) and foraging ability post-metamorphosis in two native Australian frog species, the southern brown tree frog (Litoria ewingii) and the striped marsh frog (Limnodynastes peronii). We found that both Lit. ewingii and Lim. peronii exhibited differences in metamorphic traits in response to elevated salinity. Neither species showed significant change in oxygen consumption during development in response to salinity, relative to freshwater controls. Both species displayed impaired escape response behaviours in response to salinity during larval development, but flow-on effects to adult escape response behaviours and foraging performance were species-specific. Our results show that the influence of stressors during development can have consequences for anuran physiology and behaviour at multiple life stages, and emphasize the need for studies that examine the energetics of anuran responses in order to better understand the responses of biota to stressful environments. PMID- 26998338 TI - Timing of CD8 T cell effector responses in viral infections. AB - CD8 T cell or cytotoxic T lymphocyte (CTL) responses are an important branch of the immune system in the fight against viral infections. The dynamics of anti viral CTL responses have been characterized in some detail, both experimentally and with mathematical models. An interesting experimental observation concerns the timing of CTL responses. A recent study reported that in pneumonia virus of mice the effector CTL tended to arrive in the lung only after maximal virus loads had been achieved, an observation that seems at first counterintuitive because prevention of pathology would require earlier CTL-mediated activity. A delay in CTL-mediated effector activity has also been quoted as a possible explanation for the difficulties associated with CTL-based vaccines. This paper uses mathematical models to show that in specific parameter regimes, delayed CTL effector activity can be advantageous for the host in the sense that it can increase the chances of virus clearance. The increased ability of the CTL to clear the infection, however, is predicted to come at the cost of acute pathology, giving rise to a trade-off, which is discussed in the light of evolutionary processes. This work provides a theoretical basis for understanding the described experimental observations. PMID- 26998339 TI - Language influences music harmony perception: effects of shared syntactic integration resources beyond attention. AB - Many studies have revealed shared music-language processing resources by finding an influence of music harmony manipulations on concurrent language processing. However, the nature of the shared resources has remained ambiguous. They have been argued to be syntax specific and thus due to shared syntactic integration resources. An alternative view regards them as related to general attention and, thus, not specific to syntax. The present experiments evaluated these accounts by investigating the influence of language on music. Participants were asked to provide closure judgements on harmonic sequences in order to assess the appropriateness of sequence endings. At the same time participants read syntactic garden-path sentences. Closure judgements revealed a change in harmonic processing as the result of reading a syntactically challenging word. We found no influence of an arithmetic control manipulation (experiment 1) or semantic garden path sentences (experiment 2). Our results provide behavioural evidence for a specific influence of linguistic syntax processing on musical harmony judgements. A closer look reveals that the shared resources appear to be needed to hold a harmonic key online in some form of syntactic working memory or unification workspace related to the integration of chords and words. Overall, our results support the syntax specificity of shared music-language processing resources. PMID- 26998340 TI - Effect of microstructure on the mechanical and damping behaviour of dragonfly wing veins. AB - Insect wing veins are biological composites of chitin and protein arranged in a complex lamellar configuration. Although these hierarchical structures are found in many 'venous wings' of insects, very little is known about their physical and mechanical characteristics. For the first time, we carried out a systematic comparative study to gain a better understanding of the influence of microstructure on the mechanical characteristics and damping behaviour of the veins. Morphological data have been used to develop a series of three-dimensional numerical models with different material properties and geometries. Finite element analysis has been employed to simulate the mechanical response of the models under different loading conditions. The modelling strategy used in this study enabled us to determine the effects selectively induced by resilin, friction between layers, shape of the cross section, material composition and layered structure on the stiffness and damping characteristics of wing veins. Numerical simulations suggest that although the presence of the resilin-dominated endocuticle layer results in a much higher flexibility of wing veins, the dumbbell-shaped cross section increases their bending rigidity. Our study further shows that the rubber-like cuticle, friction between layers and material gradient based design contribute to the higher damping capacity of veins. The results of this study can serve as a reference for the design of novel bioinspired composite structures. PMID- 26998341 TI - Maternal stress-associated cortisol stimulation may protect embryos from cortisol excess in zebrafish. AB - Abnormal embryo cortisol level causes developmental defects and poor survival in zebrafish (Danio rerio). However, no study has demonstrated that maternal stress leads to higher embryo cortisol content in zebrafish. We tested the hypothesis that maternal stress-associated elevation in cortisol levels increases embryo cortisol content in this asynchronous breeder. Zebrafish mothers were fed cortisol-spiked food for 5 days, to mimic maternal stress, followed by daily breeding for 10 days to monitor temporal embryo cortisol content. Cortisol treatment increased mean embryo yield, but the daily fecundity was variable among the groups. Embryo cortisol content was variable in both groups over a 10-day period. A transient elevation in cortisol levels was observed in the embryos from cortisol-fed mothers only on day 3, but not on subsequent days. We tested whether excess cortisol stimulates 11betaHSD2 expression in ovarian follicles as a means to regulate embryo cortisol deposition. Cortisol treatment in vitro increased 11beta HSD2 levels sevenfold, and this expression was regulated by actinomycin D and cycloheximide suggesting tight regulation of cortisol levels in the ovarian follicles. We hypothesize that cortisol-induced upregulation of 11betaHSD2 activity in the ovarian follicles is a mechanism restricting excess cortisol incorporation into the eggs during maternal stress. PMID- 26998342 TI - Effect of high-potency statins on HbA1c in patients with or without diabetes mellitus. AB - BACKGROUND: The increased risk of new-onset diabetes with statin use, including high-potency statins, is well known. However, the effects of high-potency statins on HbA1c are unclear. A retrospective cohort study was conducted to examine the effect of high-potency statins on HbA1c in patients with or without diabetes. The study enrolled new statin users identified via the electronic healthcare database of the general hospital in Japan. METHODS: Following identification of all individuals (n = 4,672) who had been prescribed a lipid lowering drug at least once between January 1, 2010 and July 31, 2014, new statin users were selected (n = 1,136). Patients were excluded if they had been prescribed treatment with a statin within the preceding 6-month period. HbA1c levels before and during high potency statin treatment were compared using the dependent t-test. In addition, the hazard ratio for the incidence of diabetes with high-potency statin treatment was estimated, using low-potency statins as a reference. RESULTS: In patients with diabetes (n = 153), mean HbA1c (%) levels significantly increased by 0.4 % after high-potency statin use (7.57 +/- 1.58; p = 0.0002) compared to baseline (7.18 +/- 1.37). Similarly, HbA1c (%) levels significantly increased from 5.78 +/ 0.38 to 5.92 +/- 0.45 (p < 0.0001) after high-potency statin use in patients without diabetes (n = 165). Furthermore, a trend toward an increase in HbA1c was found for all of the high-potency statins irrespective of a history of diabetes. CONCLUSIONS: The use of high-potency statins may increase HbA1c levels in patients with or without diabetes. PMID- 26998343 TI - Effects of various freezing containers for vitrification freezing on mouse oogenesis. AB - BACKGROUND: In the present study, various freezing containers were tested for mouse embryos of respective developmental stages; embryos were vitrified and then their survival rate and developmental rate were monitored. Mouse two cell, 8 cell, and blastula stage embryos underwent vitrification freezing-thawing and then their recovery rate, survival rate, development rate, and hatching rate were investigated. METHODS: EM-grid, OPS, and cryo-loop were utilized for vitrification freezing-thawing of mouse embryos. RESULTS: It was found that recovery rate and survival rate were higher in the group of cryo-loop compared to those of EM-grid (p < 0.05). Embryonic development rate, two cell embryos to blastocyst, as well as hatching rate were higher in the control group compared to the EM-grid group and OPS group (p < 0.05), yet no difference was noted between the control group and cryo-loop group. Development rate and hatching rate of eight cell morulae and blastocysts were all lower in the treatment groups than the control group whilst hatching rate of blastocysts was higher in the control group compared to the groups of EM-grid and OPS (p < 0.05); although the cryo loop group was shown to be slightly higher than other groups, it was not statistically significant. CONCLUSIONS: In the study, we investigate effects of freezing containers on vitrified embryos of respective developmental stages; it was demonstrated that higher developmental rate was shown in more progressed (or developed) embryos with more blastomeres. There was however, no difference in embryonic development rate was shown amongst containers. Taken together, further additional studies are warranted with regards to 1) manipulation techniques of embryos for various vitrification freezing containers and 2) preventive measures against contamination via liquid nitrogen. PMID- 26998344 TI - The effect of glass shape on alcohol consumption in a naturalistic setting: a feasibility study. AB - BACKGROUND: Alcohol-related harms are a major public health concern, and population-level interventions are needed to reduce excessive alcohol consumption. Glass shape is an easily modifiable target for public health intervention. Laboratory findings show beer is consumed slower from a straight glass compared to a curved glass, but these findings have not been replicated in a naturalistic setting. The purpose of this study is to investigate the feasibility of conducting a randomised controlled trial investigating the effect of glass shape on alcohol consumption in public houses. METHODS: Straight and curved half-pint and pint glasses were delivered to three public houses over two weekends. Glass type was counterbalanced over the two weekends and between the public houses. Monetary takings were recorded as an indirect measure of consumption. RESULTS: Replacing stocks of glassware in public houses was feasible and can be enacted in a short space of time. One landlord found the study too disruptive, possibly due to a laborious exchange of glassware and complaints about the new glassware from some customers. One public house's dishwasher could not accommodate the supplied curved full-pint glasses. Obtaining monetary takings from public house staff was a feasible and efficient way of measuring consumption, although reporting absolute amounts may be commercially sensitive. Monetary takings were reduced by 24 % (95 % confidence interval 77 % reduction to 29 % increase) when straight glasses were used compared to curved glasses. CONCLUSIONS: This study shows that it is feasible to carry out a trial investigating glass shape in a naturalistic environment, although a number of challenges were encountered. Brewery owners and landlords are willing to engage with public health research in settings where alcohol is consumed, such as public houses. Good communication with stakeholders was vital to acquire good data, and highlighting the potential commercial benefits of participating was vital to the study's success. A full scale evaluation of the effects of glass shape on alcohol consumption could inform local and national policy. PMID- 26998345 TI - Enhancer of zeste plays an important role in photoperiodic modulation of locomotor rhythm in the cricket, Gryllus bimaculatus. AB - INTRODUCTION: Insects show daily behavioral rhythms controlled by an endogenous oscillator, the circadian clock. The rhythm synchronizes to daily light-dark cycles (LD) and changes waveform in association with seasonal change in photoperiod. RESULTS: To explore the molecular basis of the photoperiod-dependent changes in circadian locomotor rhythm, we investigated the role of a chromatin modifier, Enhancer of zeste (Gb'E(z)), in the cricket, Gryllus bimaculatus. Under a 12 h:12 h LD (LD 12:12), Gb'E(z) was constitutively expressed in the optic lobe, the site of the biological clock; active phase (alpha) and rest phase (rho) were approximately 12 h in duration, and alpha/rho ratio was approximately 1.0. When transferred to LD 20:4, the alpha/rho ratio decreased significantly, and the Gb'E(z) expression level was significantly reduced at 6 h and 10 h after light on, as was reflected in the reduced level of trimethylation of histone H3 lysine 27. This change was associated with change in clock gene expression profiles. The photoperiod-dependent changes in alpha/rho ratio and clock gene expression profiles were prevented by knocking down Gb'E(z) by RNAi. CONCLUSIONS: These results suggest that histone modification by Gb'E(z) is involved in photoperiodic modulation of the G. bimaculatus circadian rhythm. PMID- 26998346 TI - Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire. AB - BACKGROUND: The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. METHODS: The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. RESULTS: Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. CONCLUSIONS: Starting with a system's relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID- 26998347 TI - Solitary synovial chondromatosis arising in the gluteus maximus bursa: computed tomography and magnetic resonance imaging findings. AB - Chondral tumors in soft tissue are referred to as soft-tissue chondromas or extraskeletal chondromas, or as synovial chondromatosis if they arise in synovial tissue. We report the case of a 29-year-old man with synovial chondromatosis, also called synovial osteochondromatosis, which appeared in a solitary and extra articular form. On magnetic resonance imaging (MRI) and computed tomography, the central portion of the tumor showed similar characteristics to bone marrow, despite the absence of any connection to adjacent bone. T2-weighted imaging displayed marked peripheral hyperintensity consistent with a cartilaginous area. These findings suggested the presence of enchondral ossification and were similar to those of skeletal osteochondroma, with the exception of the absence of attachment to bone. MRI is useful for distinguishing solitary synovial chondromatosis from other lesions, such as myositis ossificans, extraskeletal chondrosarcoma, and parosteal osteosarcoma. PMID- 26998348 TI - The MDM2 small-molecule inhibitor RG7388 leads to potent tumor inhibition in p53 wild-type neuroblastoma. AB - Neuroblastoma is an aggressive pediatric malignancy which is >98% p53 wild-type at diagnosis. As a primary repressor of p53 activity and part of a p53-activated negative feedback loop, targeting of mouse double minute 2 homolog (MDM2) is an attractive therapeutic approach to reactivation of p53. Since development of the first selective MDM2 inhibitor, Nutlin-3a, newer compounds have been developed for increased potency and improved bioavailability. Herein, we sought to determine the efficacy and specificity of a second-generation MDM2 inhibitor, RG7388, in neuroblastoma cell lines and xenografts and examine its effect on the p53-independent pathway of hypoxia-inducible factor-1 alpha (HIF-1alpha)/vascular endothelial growth factor (VEGF). Cell viability and apoptosis studies were performed on the neuroblastoma cell lines, NGP, SH-SY5Y, LAN-5, LAN-5 si-p53 (p53 silenced), and SK-N-AS (p53 null). RG7388 potently decreased cell proliferation and activated p53-dependent apoptosis. Tumor-bearing mice treated with RG7388 demonstrated significant tumor inhibition by 59% in NGP (P = 0.003), 67% in SH SY5Y (P = 0.006), and 75% in LAN-5 (P = 0.0019) p53 wild-type xenograft tumors, but no inhibitory effect on LAN-5 si-p53 or SK-N-AS p53-silenced/null xenograft tumors. Moreover, RG7388 was found to inhibit the p53-independent pathway of HIF 1alpha/VEGF with decreased gene expression and alteration of angiogenesis. Our study supports the further evaluation of RG7388 as a novel treatment option in p53 wild-type neuroblastoma at diagnosis and relapse. PMID- 26998349 TI - Quantitative Trait Locus and Brain Expression of HLA-DPA1 Offers Evidence of Shared Immune Alterations in Psychiatric Disorders. AB - Genome-wide association studies of schizophrenia encompassing the major histocompatibility locus (MHC) were highly significant following genome-wide correction. This broad region implicates many genes including the MHC complex class II. Within this interval we examined the expression of two MHC II genes (HLA-DPA1 and HLA-DRB1) in brain from individual subjects with schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and controls by differential gene expression methods. A third MHC II mRNA, CD74, was studied outside of the MHC II locus, as it interacts within the same immune complex. Exon microarrays were performed in anterior cingulate cortex (ACC) in BD compared to controls, and both HLA-DPA1 and CD74 were decreased in expression in BD. The expression of HLA-DPA1 and CD74 were both reduced in hippocampus, amygdala, and dorsolateral prefrontal cortex regions in SZ and BD compared to controls by specific qPCR assay. We found several novel HLA-DPA1 mRNA variants spanning HLA DPA1 exons 2-3-4 as suggested by exon microarrays. The intronic rs9277341 SNP was a significant cis expression quantitative trait locus (eQTL) that was associated with the total expression of HLA-DPA1 in five brain regions. A biomarker study of MHC II mRNAs was conducted in SZ, BD, MDD, and control lymphoblastic cell lines (LCL) by qPCR assay of 87 subjects. There was significantly decreased expression of HLA-DPA1 and CD74 in BD, and trends for reductions in SZ in LCLs. The discovery of multiple splicing variants in brain for HLA-DPA1 is important as the HLA-DPA1 gene is highly conserved, there are no reported splicing variants, and the functions in brain are unknown. Future work on the function and localization of MHC Class II proteins in brain will help to understand the role of alterations in neuropsychiatric disorders. The HLA-DPA1 eQTL is located within a large linkage disequilibrium block that has an irrefutable association with schizophrenia. Future tests in a larger cohort are needed to determine the significance of this eQTL association with schizophrenia. Our findings support the long-held hypothesis that alterations in immune function are associated with the pathophysiology of psychiatric disorders. PMID- 26998350 TI - National Eye Institute Visual Function Scale in Type 2 Diabetes Patients. AB - Aim. To examine subscale and total scores of NEI-VFQ questionnaire of type 2 diabetes patients at different diabetic retinopathy (DRP) stages. Methods. A total number of 201 patients have been included. Prior to ophthalmological examination all patients participated in the NEI-VFQ questionnaire. The patients were divided into 5 groups according to the International Clinical Diabetic Retinopathy Disease Severity Scale (ICDRS). Results. The diabetes duration in general health scores (p = 0.029); the stage (p = 0.011); and clinically significant macular edema (CSME) (p = 0.019) in general vision were found to be the most efficient factors. In near vision activities the most efficient factors were near vision acuity (NVA) (p = 0.0001) and DRP stage (p = 0.020). EDTRS visual acuity was found to be the most efficient factor in vision specific role difficulties (p = 0.034) and dependency (p = 0.011) whereas Snellen visual acuity was found to be among the most effective factors in distance activities (DA) (p = 0.014) and total scores (p = 0.026). Discussion. Difference was based not on the diabetes duration, clinically significant cataract (CSCat), CSME presence, and DRP stage but on the visual acuity levels of the better seeing eye of the patients. PMID- 26998351 TI - Diplopia as the Complication of Cataract Surgery. AB - The authors present systematic review of aetiology and treatment of diplopia related to cataract surgery. The problem is set in the modern perspective of changing cataract surgery. Actual incidence is discussed as well as various modalities of therapeutic options. The authors provide the guidance for the contemporary cataract surgeon, when to expect potential problem in ocular motility after cataract surgery. PMID- 26998352 TI - Optic Disc Vascularization in Glaucoma: Value of Spectral-Domain Optical Coherence Tomography Angiography. AB - Purpose. To detect changes in optic nerve head (ONH) vascularization in glaucoma patients using spectral-domain OCT angiography (OCT-A). Material and Method. Fifty glaucoma patients and 30 normal subjects were evaluated with OCT-A (AngioVue(r), Optovue). The total ONH vessel density and temporal disc vessel density were measured. Clinical data, visual field (VF) parameters, and spectral domain OCT evaluation (RNFL: retinal nerve fiber layer thickness, GCC: ganglion cell complex thickness, and rim area) were recorded for glaucoma patients. Correlations among total and temporal ONH vessel density and structural and VF parameters were analyzed. Results. In the glaucoma group, total and temporal ONH vessel density were reduced by 24.7% (0.412 versus 0.547; p < 0.0001) and 22.88% (0.364 versus 0.472; p = 0.001), respectively, as compared with the control group. Univariate analysis showed significant correlation between rim area (mm(2)) and temporal ONH vessel density (r = 0.623; p < 0.0001) and total ONH vessel density (r = 0.609; p < 0.0001). Significant correlations were found between temporal and total ONH vessel density and RNFL, GCC, VF mean deviation, and visual field index. Conclusion. In glaucoma patients OCT-A might detect reduced ONH blood vessel density that is associated with structural and functional glaucomatous damage. OCT-A might become a useful tool for the evaluation of ONH microcirculation changes in glaucoma. PMID- 26998353 TI - Visual Recovery after Primary Retinal Detachment Surgery: Biofeedback Rehabilitative Strategy. AB - Purpose. To evaluate possible speeding up recovery time after retinal detachment (RD) surgery using biofeedback strategy. Methods. A total of 52 eyes were selected. After surgery, patients were divided into two groups: group A, including patients submitted to biofeedback with MP-1 strategy; group B, patients who received common care strategy. Biofeedback strategy was started 15 days after the suspension of cycloplegic eye drops in buckling procedure or after silicone oil removal in the vitrectomized eyes. Controls were scheduled at baseline and 6, 12, and 18 weeks. Results. At baseline, there was no significant difference in BCVA between groups (P = 0.4230). At the end of biofeedback treatment (WK 6) BCVA of group A was significantly better (P < 0.001) than group B and BCVA was still better in group A than group B at WK 12 (P = 0.028) and at WK 18 (P = 0.041). Conclusions. Visual recovery after RD surgery is still unclear, and it does not depend on entity of the RD. Our data demonstrate that in biofeedback group there was a significant recovery in visual performances that still remains evident after 3 months from the baseline. PMID- 26998354 TI - Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis. AB - Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface. PMID- 26998355 TI - Cholesterol Lowering Effect of Plant Stanol Ester Yoghurt Drinks with Added Camelina Oil. AB - The aim of this study was to investigate the effects of yoghurt minidrinks containing two doses of plant stanol ester either with or without added camelina oil on the serum cholesterol levels in moderately hypercholesterolemic subjects. In this randomised, double-blind, parallel group study, 143 subjects consumed a 65 mL minidrink together with a meal daily for four weeks. The minidrink contained 1.6 or 2.0 grams of plant stanols with or without 2 grams of alpha linolenic acid-rich camelina oil. The placebo minidrink did not contain plant stanols or camelina oil. All plant stanol treated groups showed statistically significant total, LDL, and non-HDL cholesterol lowering relative to baseline and relative to placebo. Compared to placebo, LDL cholesterol was lowered by 9.4% (p < 0.01) and 8.1% (p < 0.01) with 1.6 g and 2 g plant stanols, respectively. With addition of Camelina oil, 1.6 g plant stanols resulted in 11.0% (p < 0.01) and 2 g plant stanols in 8.4% (p < 0.01) reduction in LDL cholesterol compared to placebo. In conclusion, yoghurt minidrinks with plant stanol ester reduced serum LDL cholesterol significantly and addition of a small amount of camelina oil did not significantly enhance the cholesterol lowering effect. This trial was registered with ClinicalTrials.gov NCT02628990. PMID- 26998356 TI - Liver Cirrhosis and Diabetes Mellitus Are Risk Factors for Staphylococcus aureus Infection in Patients with Healthcare-Associated or Hospital-Acquired Pneumonia. AB - BACKGROUND: The risk factors for Staphylococcus aureus (S. aureus) pneumonia are not fully identified. The aim of this work was to find out the clinical characteristics associated with S. aureus infection in patients with healthcare associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), which may be applicable for more appropriate selection of empiric antibiotic therapy. METHODS: From July 2007 to June 2010, patients who were admitted to the intensive care unit with severe HCAP/HAP and severe sepsis were enrolled in this study. Lower respiratory tract sample was semiquantitatively cultured. Initial broad-spectrum antibiotics were chosen by Taiwan or American guidelines for pneumonia management. Standard bundle therapies were provided to all patients according to the guidelines of the Surviving Sepsis Campaign. RESULTS: The most frequently isolated pathogens were Pseudomonas aeruginosa, S. aureus, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Patients with positive isolation of S. aureus in culture had significantly higher history of liver cirrhosis and diabetes mellitus, with odds ratios of 3.098 and 1.899, respectively. The S. aureus pneumonia was not correlated with history of chronic obstructive pulmonary disease, hypertension, and hemodialysis. CONCLUSION: Liver cirrhosis and diabetes mellitus may be risk factors for S. aureus infection in patients with severe HCAP or HAP. PMID- 26998357 TI - Changes in the Physicochemical Properties of Piperine/beta-Cyclodextrin due to the Formation of Inclusion Complexes. AB - Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and beta cyclodextrin (betaCD) (molar ratio of PP/betaCD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and betaCD were observed. Based on Job's plot, the PP/betaCD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH2), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure betaCD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and betaCD cavity was detected by (1)H-(1)H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy. PMID- 26998358 TI - Design and Microwave Assisted Synthesis of Coumarin Derivatives as PDE Inhibitors. AB - Coumarins appended to benzimidazole through pyrazole are designed and synthesized using microwave irradiation. These compounds were analyzed for phosphodiesterase (PDE) inhibition indirectly by motility pattern in human spermatozoa. Some of the synthesized compounds, namely, 5d, 5e, 5f, 5g, 5h, and 5k, have exhibited potent inhibitory activity on PDE. PMID- 26998360 TI - Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients. AB - Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow mediated dilation (FMD), plasma lipids, vitamin E (alpha- and gamma-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-gamma tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 +/ 11 y). Results. Relative to Pre, total cholesterol (7.8 +/- 1.5 mmol/L) and LDL cholesterol (6.2 +/- 1.2 mmol/L) were 61% and 70% lower (P < 0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 +/- 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma alpha-tocopherol, gamma-tocopherol, and NGT concentrations were 52-69% lower at Post (P < 0.01), and alpha-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia. PMID- 26998359 TI - Understanding Muscle Dysfunction in Chronic Fatigue Syndrome. AB - Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level. Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis. Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction. Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME. PMID- 26998361 TI - Prevalence of Vitamin D Deficiency in Elderly Patients Admitted to an Inpatient Rehabilitation Unit in Tropical Singapore. AB - Background. Data on hypovitaminosis D in elderly patients admitted to rehabilitation units in tropical countries are scarce. Objective. To assess the prevalence of vitamin D deficiency and its associated risk factors in elderly patients admitted to a rehabilitation unit in tropical Singapore. Methods. Prospective, cohort study of 134 subjects >= 65 years old admitted to a tertiary rehabilitation centre. Serum 25-hydroxyvitamin D3 (25OHD3) was measured on rehabilitation admission. Results. Mean age was 72.0 +/- 5.7 years, and stroke was the commonest rehabilitation diagnosis (49.3%). Low 25OHD3 levels were present in 115 patients (85.6%) and 59 patients (44%) were deemed to be vitamin D deficient. The mean PTH level was significantly higher in patients with low 25OHD3 levels. (p = 0.002) Age, gender, vitamin D supplementation, premorbid ambulatory status, and admission/discharge Functional Independence Measure scores were not significantly associated with vitamin D deficiency. Malays/Indians (p = 0.013) and recurrent fallers (p = 0.029) were at significantly higher risk of vitamin D deficiency. Conclusions. Despite the tropical weather, vitamin D deficiency is common in elderly subjects admitted to a rehabilitation unit in Singapore. Routine assessment of vitamin D levels is recommended especially in those with a history of recurrent falls and patients of Indian/Malay ethnicity. PMID- 26998362 TI - Role of Microvessel Density and Vascular Endothelial Growth Factor in Angiogenesis of Hematological Malignancies. AB - Angiogenesis plays an important role in progression of tumor with vascular endothelial growth factor (VEGF) being key proangiogenic factor. It was intended to study angiogenesis in different hematological malignancies by quantifying expression of VEGF and MVD in bone marrow biopsy along with serum VEGF levels and observing its change following therapy. The study included 50 cases of hematological malignancies which were followed for one month after initial therapy along with 30 controls. All of them were subjected to immunostaining by anti-VEGF and factor VIII antibodies on bone marrow biopsy along with the measurement of serum VEGF levels. Significantly higher pretreatment VEGF scores, serum VEGF levels, and MVD were observed in cases as compared to controls (p < 0.05). The highest VEGF score and serum VEGF were observed in chronic myeloid leukemia and maximum MVD in Non-Hodgkin's Lymphoma. Significant decrease in serum VEGF levels after treatment was observed in all hematological malignancies except for AML. To conclude angiogenesis plays an important role in pathogenesis of all the hematological malignancies as reflected by increased VEGF expression and MVD in bone marrow biopsy along with increased serum VEGF level. The decrease in serum VEGF level after therapy further supports this view and also lays the importance of anti angiogenic therapy. PMID- 26998363 TI - Tracheobronchial amyloidosis: A case report and review of the literature. AB - OBJECTIVES: This is a case report on tracheobronchial amyloidosis. This disease may provide a diagnostic challenge for otolaryngologists due to its rarity and relative lack of literature. Our case highlights presentation and workup of this disease. METHODS: The index patient's workup included clinical exam, CT of the neck and chest, direct laryngoscopy, bronchoscopy and biopsy. Additional reports of tracheobronchial amyloidosis were identified in a PubMed database search. RESULTS: Our index patient presented with dyspnea and hoarseness. Clinic laryngoscopy showed a tracheal mass. Radiology demonstrated an irregular tracheal soft tissue lesion. The patient underwent biopsy, and pathology was consistent with amyloidosis. He had no systemic signs of amyloidosis. He underwent local resection to improve his airway diameter, with no complications. CONCLUSIONS: Tracheobronchial amyloidosis should be kept in an otolaryngologist's differential diagnosis for patients with nonspecific upper airway symptomatology and radiographic lesions in the trachea or bronchi. PMID- 26998364 TI - Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity. AB - GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca(2+)]i) and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca(2+)]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs) by 73.2 +/- 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition), mediated by endogenous cannabinoids that require a [Ca(2+)]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI) persisted in the absence of a [Ca(2+)]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores) failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca(2+)-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels. PMID- 26998366 TI - Amphetamine Abuse Related Acute Myocardial Infarction. AB - Amphetamine abuse is a global problem. The cardiotoxic manifestations like acute myocardial infarction (AMI), heart failure, or arrhythmia related to misuse of amphetamine and its synthetic derivatives have been documented but are rather rare. Amphetamine-related AMI is even rarer. We report two cases of men who came to emergency department (ED) with chest pain, palpitation, or seizure and were subsequently found to have myocardial infarction associated with the use of amphetamines. It is crucial that, with increase in amphetamine abuse, clinicians are aware of this potentially dire complication. Patients with low to intermediate risk for coronary artery disease with atypical presentation may benefit from obtaining detailed substance abuse history and urine drug screen if deemed necessary. PMID- 26998365 TI - State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect. AB - The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression. PMID- 26998367 TI - Dental Treatment of a Child with Pallister-Killian Syndrome. AB - The Pallister-Killian syndrome (PKS) is an extremely rare genetic disorder with an incidence estimated around 1/25000. PKS is a multiple congenital anomaly deficit syndrome caused by mosaic tissue limited tetrasomy for chromosome 12p. The presented report is the first confirmed case with PKS in Turkey. This report focuses on the orofacial clinical manifestations of an 6-year-old boy with PKS who was referred to the Department of Paediatric Dentistry clinic, Gazi University. It has been learned that the PKS was diagnosed 1 year after birth. Due to intellectual disability, it was decided to make the dental treatments under moderate sedation. Although significant tongue thrust and anterior open bite were determined, any oral appliances could not be applied because of the 2 epilepsy seizures in the last 2 years. The aim was to treat decayed teeth and set good oral hygiene in the patient's mouth. Still, there is a probability for epilepsy seizures. If epileptic seizures stop permanently, we can apply an oral appliance to block tongue thrust. The patient is now under control. In cases of systemic and oral findings such as PKS, conducting medical and dental approaches together will increase the life quality of patients. PMID- 26998368 TI - False Negative Cell-Free DNA Screening Result in a Newborn with Trisomy 13. AB - Background. Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy. Results. We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism. Conclusions. Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information. PMID- 26998369 TI - Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients. AB - The etiologies of secondary idiopathic thrombocytopenic purpura (ITP) include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/MUL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/MUL) after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/MUL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP) eradication or corticosteroid treatment, all of the patients' platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations. PMID- 26998371 TI - Hematocolpos as a Result of Delayed Treatment of Acute Straddle Injury in an Adolescent Girl. AB - Accidental genital trauma is most commonly caused by straddle-type injuries and is usually treatable by nonoperative management, and most of the injuries have a good prognosis. When the bleeding occurred due to straddle injury in adolescent girl, experienced gynecological examination and treatment were very important. We experienced a case of straddle injury to the posterior fourchette that caused acute hematocolpos due to delayed adequate treatment with hypotension and acute abdomen in an adolescent girl. This case shows the importance of careful and accurate physical and gynecological examination and adequate and prompt treatment of genital trauma in adolescent girls. PMID- 26998370 TI - Severe Sepsis due to Clostridium perfringens Bacteremia of Urinary Origin: A Case Report and Systematic Review. AB - Clostridium perfringens bacteremia is an uncommon yet serious clinical syndrome that typically arises from a gastrointestinal source. However, clinicians should consider nongastrointestinal sources as well. We present a rare case of C. perfringens bacteremia of urinary origin that required surgical intervention for definitive treatment. A 61-year-old male presented with acute nausea and vomiting, altered mental status, and chronic diarrhea. His physical exam revealed right costovertebral tenderness and his laboratory work-up revealed acute renal failure. Percutaneous blood cultures grew C. perfringens. Cross-sectional imaging revealed a right-sided ureteral stone with hydronephrosis, which required nephrostomy placement. On placement of the nephrostomy tube, purulent drainage was identified and Gram stain of the drainage revealed Gram-variable rods. A urinary source of C. perfringens was clinically supported. Although it is not a common presentation, nongastrointestinal sources such as a urinary source should be considered in C. perfringens bacteremia because failure to recognize a nongastrointestinal source can delay appropriate treatment, which may include surgical intervention. PMID- 26998372 TI - Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome. AB - Sjogren's syndrome (SS) has the highest incidence of malignant lymphoproliferative disorders transformation among autoimmune diseases. We present a case of extranodal high grade lymphoma of the liver in a 52-year-old patient with long history of SS. Lymphoma manifested with sharp significant pain in the right hypochondrium, weakness, and profuse night sweats. Contrast-enhanced computed tomography scan (CT-scan) of the abdomen revealed multiple low density foci with homogeneous structure and clear contours in both lobes of the liver. Histologically, proliferation of medium sized lymphoma cells with round-oval and slightly irregular nuclei with fine chromatin was shown. Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL). To exclude secondary liver lesion by non-Hodgkin lymphoma, chest and small pelvis CT-scan, endoscopy of upper and lower gastrointestinal tract and study of bone marrow were performed. After 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the complete remission was achieved, which persists after 45 months of follow-up. Primary hepatic lymphomas are extremely rare, and previously only low-grade hepatic lymphomas have been described in SS. To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS. PMID- 26998373 TI - A Rare Concurrence of Leiomyomatosis Peritonealis Disseminata, Leiomyosarcoma of the Pelvis and Leiomyomatous Nodule of the Liver. AB - Leiomyomatosis peritonealis disseminata (LPD) is a rare entity that is characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules throughout the peritoneal surface mimicking a malignant process. LPD follows a benign course in general, and it is often found incidentally during abdominal surgery. There have been reported cases of LPD with malignant degeneration although the association is uncertain. Concurrent finding of LPD and leiomyosarcoma of the pelvis is very rare that could be coincidental, malignant transformation of LPD to leiomyosarcoma, or progression of undetected primary leiomyosarcoma. There are only a few previously reported cases in the literature. Herein, we report a case of 56-year-old woman with a history of leiomyoma of uterus who presented with progressive abdominal swelling secondary to mass lesions in the pelvis. The patient underwent exploratory laparotomy and debulking of the tumors, and the histologic examination of the tumors revealed coexistence of LPD and leiomyosarcoma. After recovery from the operation, core needle biopsy of the superficial, residual liver mass was obtained to investigate potential liver metastasis, and the histopathologic findings are consistent with leiomyoma which represents the first simultaneous occurrence of LPD, leiomyosarcoma, and leiomyomatous nodule of the liver. PMID- 26998374 TI - Angiomyolipoma and Malignant PEComa: Discussion of Two Rare Adrenal Tumors. AB - Angiomyolipoma and PEComa are rare tumors descending from perivascular epithelial cells (PECs), with distinctive IHC, morphological, and ultrastructural features. The kidney is the most frequent site of origin, but not the only one; however, adrenal gland angiomyolipomas are extremely rare. We describe two cases being found in the adrenal glands. Given the paucity of literature on the subject, more information on this disease is necessary for diagnosis and treatment. Here, we describe two complete case reports, from presentation to treatment and follow-up, along with imaging and microscopic pathology samples, and provide a comprehensive review as to the history and current literature available regarding these extremely rare tumors. PMID- 26998375 TI - Hyperprolactinemia Secondary to Allergic Fungal Sinusitis Compressing the Pituitary Gland. AB - Objective. We aim to describe the first case in the literature of allergic fungal sinusitis (AFS) presenting with hyperprolactinemia due to compression of the pituitary gland. Case Presentation. A 37-year-old female presented with bilateral galactorrhea and occipital headaches of several weeks. Workup revealed elevated prolactin of 94.4, negative pregnancy test, and normal thyroid function. MRI and CT demonstrated a 5.0 * 2.7 * 2.5 cm heterogeneous expansile mass in the right sphenoid sinus with no pituitary adenoma as originally suspected. Patient was placed on cabergoline for symptomatic control until definitive treatment. Results. The patient underwent right endoscopic sphenoidotomy, which revealed nasal polyps and fungal debris in the sphenoid sinus, consistent with AFS. There was bony erosion of the sella and clivus. Pathology and microbiology were consistent with allergic fungal sinusitis caused by Curvularia species. Prolactin levels normalized four weeks after surgery with resolution of symptoms. Conclusion. Functional endoscopic sinus surgery alone was able to reverse the patient's pituitary dysfunction. To our knowledge, this is the first case of AFS presenting as hyperprolactinemia due to pituitary compression. PMID- 26998376 TI - Foregut Duplication Cyst of the Stomach: A Case Report and Review of the Literature. AB - Duplication cyst of the stomach is a rare congenital malformation, typically diagnosed in the first year of life. In most adult cases the cyst remains asymptomatic, but patients may present with abdominal symptoms including epigastric discomfort or pain. We present a case of a 65-year-old male with an asymptomatic gastric tumor diagnosed incidentally during initial workup of his esophageal adenocarcinoma. Computed tomography revealed a low density soft tissue tumor near the gastroesophageal junction. Endoscopic ultrasonography demonstrated a cystic lesion as a hypoechoic round mass with well-defined borders. Following complete laparoscopic resection, microscopic review revealed a cyst lined with respiratory pseudostratified ciliated columnar epithelium and layers of smooth muscle with an outermost thin fibrous capsule consistent with a foregut duplication cyst. PMID- 26998377 TI - The Effect of Periodontitis on Expression of Interleukin-21: A Systematic Review. AB - Purpose. Inflammation and tissue breakdown are led by an array of inflammatory destructive mediators associated with initiation and progression of inflammatory diseases like periodontitis. Current evidence shows that these inflammatory mediators have a definitive role in the pathogenesis of various systemic diseases with an inflammatory component. Interleukin-21 (IL-21) has been associated with systemic diseases like rheumatoid arthritis and Crohn's disease that follow a chronic inflammatory cascade. Similarly recent studies have associated Interleukin-21 levels with periodontitis. This systematic review was aimed to assess the levels of IL-21 in subjects with periodontitis. Methods. A complete literature search was done in PubMed, Medline, Science Direct, and Cochrane databases and Google Scholar based on the inclusion/exclusion criteria. Six relevant articles were procured. Full text was read individually by two reviewers and data extraction was done based on STROBE statement. Results. After data extraction five observational and one interventional study were obtained. All the studies showed an increased expression of IL-21 in periodontitis and the interventional study showed reduction in IL-21 levels after nonsurgical periodontal therapy (NSP). Conclusion. Interleukin-21 levels are higher in periodontitis than controls. With this limited evidence further longitudinal studies are required to consider this as a definitive inflammatory marker. PMID- 26998378 TI - Insula Volume and Salience Network Are Associated with Memory Decline in Parkinson Disease: Complementary Analyses of Voxel-Based Morphometry versus Volume of Interest. AB - Objective. We investigated structural brain change in subjects with a clinical diagnosis of Parkinson disease with mild cognitive impairment (PD-MCI) and examined its relationship with memory impairment. Methods. Twenty-three PD-MCI patients were enrolled and underwent cognitive evaluation and 3-dimensional T1 weighted imaging. Voxel-based morphometry (VBM) was used to assess brain-behavior correlations and examine the relationship between insula and memory score. VOI methods replicated results obtained from VBM. Results. VBM uncovered the notion that memory scores were positively correlated with the gray matter (GM) density in the insular cortex and a significant positive correlation between overall cognitive performance and concentration of GM within the lateral temporal cortex. In VOI analyses, our results suggested a positive correlation between the insula and composite free-recall verbal memory (rho = 0.617, P = 0.003) and the delayed free-recall verbal memory subdomain (rho = 0.725, P < 0.001). Furthermore, we found a positive correlation between the insula and caudate (sigma = 0.570, P = 0.006) and putamen volume (sigma = 0.683, P < 0.001). Conclusions. In patients with PD-MCI, atrophic changes in the insula may be related to memory deficits, and the brain-behavior correlation may be associated with atrophic change in the striatum within the salience network. PMID- 26998379 TI - Respiratory Support for Pharmacologically Induced Hypoxia in Neonatal Calves. AB - Practical methods to provide respiratory support to bovine neonates in a field setting are poorly characterised. This study evaluated the response of healthy neonatal calves with pharmacologically induced respiratory suppression to nasal oxygen insufflation and to continuous positive airway pressure (CPAP) delivered via an off-the-shelf device. Ten calves were randomised to receive either nasal oxygen insufflation (Group 1, n = 5) or CPAP (Group 2, n = 5) as a first treatment after induction of respiratory depression by intravenous administration of xylazine, fentanyl, and diazepam. Calves received the alternate treatment after 10 minutes of breathing ambient air. Arterial blood gas samples were obtained prior to sedation, following sedation, following the first and second treatment, and after breathing ambient air before and after the second treatment. Oxygen insufflation significantly increased arterial oxygen partial pressure (PaO2) but was also associated with significant hypercapnia. When used as the first treatment, CPAP was associated with significantly decreased arterial partial pressure of carbon dioxide but did not increase PaO2. These results suggest that the use of CPAP may represent a practical method for correction of hypercapnia associated with inadequate ventilation in a field setting, and further research is required to characterise the use of CPAP with increased inspired oxygen concentrations. PMID- 26998380 TI - Protozoan Parasites of Rodents and Their Zoonotic Significance in Boyer-Ahmad District, Southwestern Iran. AB - Backgrounds. Wild rodents are reservoirs of various zoonotic diseases, such as toxoplasmosis, babesiosis, and leishmaniasis. The current study aimed to assess the protozoan infection of rodents in Boyer-Ahmad district, southwestern Iran. Materials and Methods. A total of 52 rodents were collected from different parts of Boyer-Ahmad district, in Kohgiluyeh and Boyer-Ahmad province, using Sherman live traps. Each rodent was anesthetized with ether, according to the ethics of working with animals, and was dissected. Samples were taken from various tissues and stool samples were collected from the contents of the colon and small intestines. Moreover, 2 to 5 mL of blood was taken from each of the rodents and the sera were examined for anti-Leishmania antibodies, by ELISA, or anti-T. gondii antibodies, by modified agglutination test (MAT). DNA was extracted from brain tissue samples of each rodent and PCR was used to identify the DNA of T. gondii. Results. Of the 52 stool samples of rodents studied by parasitological methods, intestinal protozoa infection was seen in 28 cases (53.8%). From 52 rodents, 19 (36.5%) were infected with Trichomonas, 10 (19.2%) with Giardia muris, and 11 (21.2%) with Entamoeba spp. Also, 10 cases (19.2%) were infected with Blastocystis, 3 (5.8%) were infected with Chilomastix, 7 (13.5%) were infected with Endolimax, 1 (1.9%) was infected with Retortamonas, 3 (5.77%) were infected with T. gondii, and 6 (11.54%) were infected with Trypanosoma lewisi. Antibodies to T. gondii were detected in the sera of 5 (9.61%) cases. Results of the molecular study showed T. gondii infection in 3 (5.77%) of the rodents. Findings of this study showed that rodents in Kohgiluyeh and Boyer-Ahmad province, southwestern Iran, are infected with several blood and intestinal parasites; some of them might be potential risks to residents and domestic animals in the region. PMID- 26998381 TI - Research Trends in Emerging Contaminants on the Aquatic Environments of Tanzania. AB - The continuity for discovery and production of new chemicals, allied products, and uses has currently resulted into generation of recent form of contaminants known as Emerging Contaminants (ECs). Once in the aquatic environment ECs are carcinogenic and cause other threats to both human's and animals' health. Due to their effects this study was aimed at investigating research trends of ECs in Tanzania. Findings revealed that USA and EU countries were leading in ECs researches, little followed by Asia, South Africa, and then Zambia. Only few guidelines from USA-EPA, WHO, Canada, and Australia existed. Neither published guidelines nor regulations for ECs existed in Tanzania; rather only the occurrence of some disinfection by-products and antibiotics was, respectively, reported in Arusha and Dar es Salaam, Tanzania. As these reports had a limited coverage of ECs, henceforth, these findings constitute the first-line reference materials for ECs research in Tanzania which shall be useful for future monitoring and regulation planning. PMID- 26998382 TI - The Role of Untimed Blood Glucose in Screening for Gestational Diabetes Mellitus in a High Prevalent Diabetic Population. AB - Global prevalence increase of diabetes type 2 and gestational diabetes (GDM) has led to increased awareness and screening of pregnant women for GDM. Ideally screening for GDM should be done by an oral glucose tolerance test (oGTT), which is laborious and time consuming. A randomized glucose test incorporated with anthropomorphic characteristics may be an appropriate cost-effective combined clinical and biochemical screening protocol for clinical practice as well as cutting down on oGTTs. A retrospective observational study was performed on a randomized sample of pregnant women who required an OGTT during their pregnancy. Biochemical and anthropomorphic data along with obstetric outcomes were statistically analyzed. Backward stepwise logistic regression and receiver operating characteristics curves were used to obtain a suitable predictor for GDM without an oGTT and formulate a screening protocol. Significant GDM predictive variables were fasting blood glucose (p = 0.0001) and random blood glucose (p = 0.012). Different RBG and FBG cutoff points with anthropomorphic characteristics were compared to carbohydrate metabolic status to diagnose GDM without oGTT, leading to a screening protocol. A screening protocol incorporating IADPSG diagnostic criteria, BMI, and different RBG and FBG criteria would help predict GDM among high-risk populations earlier and reduce the need for oGTT test. PMID- 26998383 TI - Measurements of Pupillary Diameter and Wavefront Aberrations in Pregnant Women. AB - Purpose. To show whether pregnancy affects the measurements of pupillary diameter and wavefront (WF) aberrations. Methods. This was a case-control study including 34 healthy pregnant women in the third trimester and age-matched 34 nonpregnant women. Only women who had no ocular abnormalities and no refractive error were included. We measured photopic and mesopic pupil diameter and WF aberrations at the third trimester and at the second postpartum month. Measurements of the right eyes were used in this study. The differences between groups were analysed by paired t-test and t-test. Results. Pregnant women's mean photopic pupil size in the third trimester was significantly higher than in postpartum period and in control group (3.74 +/- 0.77, 3.45 +/- 0.53, and 3.49 +/- 0.15 mm, p < 0.05, resp.). Mesopic pupil size in the third trimester was also higher than in postpartum period and in control group (6.77 +/- 0.52, 6.42 +/- 0.55, and 6.38 +/ 0.21 mm, p < 0.05, resp.). RMS-3 and RMS-5 values were higher in pregnancy but these differences were not statistically significant. Conclusion. Pregnancy increased photopic and mesopic pupil size significantly but did not increase wavefront aberrations notably. Increased pupil size may be due to increased sympathetic activity during pregnancy. And this activity can be noninvasively determined by measuring pupil size. PMID- 26998384 TI - Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time. AB - OBJECTIVES: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. METHODS: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. RESULTS: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = +/- 0.71; however, clotting was observed in the control group 13.8 s, SDs = +/- 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 MUg/mouse. CONCLUSION: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro. PMID- 26998385 TI - Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats. AB - OBJECTIVES: This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. METHODS: SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). RESULTS: OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. CONCLUSION: The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes. PMID- 26998386 TI - The Success of Thread-embedding Therapy in Generating Hair Re-growth in Mice Points to Its Possibly Having a Similar Effect in Humans. AB - OBJECTIVES: Recently, thread-embedding therapy (TET) has been widely applied in Korean medicine for cosmetic purposes such as reducing skin wrinkles. An inserted thread was reported to have induced continuous stimulation, followed by support for connective tissue regeneration. However, the potential role of TET in hairgrowth has not yet been reported. METHODS: We designed this study to evaluate whether TET has a hair-growth-promoting effect. C57 black 6 (C57BL/6) mice were divided into three groups: normal saline-treated, minoxidil-treated, and thread embedded groups. Normal saline or 5% minoxidil was topically sprayed on the dorsal skin of the mice once a day for 16 days. Medical threads were embedded into the dorsal skin of the mice in a single application. Hair growth activity was evaluated by using dermoscopic and microscopic observations. Sections of the dorsal skin were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7), and fibroblast growth factor-5 (FGF-5) were detected by using immunohistochemical staining. A reverse transcription-polymerase chain reaction (RT-PCR) analysis was adopted to measure the messenger RNA (mRNA) expressions of FGF-7 and FGF-5. RESULTS: TET enhanced anagen development in the hair follicles of C57BL/6 mice. The expressions of BrdU and PCNA, both of which imply active cellular proliferation, were increased by using TET. Moreover, TET increased the expression of FGF-7, an anagen-inducing growth factor, while decreasing the expression of FGF-5, an anagen-cessation growth factor, both at the protein and the mRNA levels. CONCLUSION: TET enhanced hair re-growth in C57BL/6 mice. TET regulated the expressions of anagen-associated growth factors and activated the proliferation of hair follicular cells in depilated skin lesions. Considering its long-lasting effect, TET may be a good alternative therapeutic for the treatment of alopecia. PMID- 26998387 TI - Evaluation of Women with Myofascial Abdominal Syndrome Based on Traditional Chinese Medicine. AB - OBJECTIVES: This study used semiology based on traditional Chinese medicine (TCM) to investigate vital energy (Qi) behavior in women with abdominal myofascial pain syndrome (AMPS). METHODS: Fifty women diagnosed with chronic pelvic pain (CPP) secondary to AMPS were evaluated by using a questionnaire based on the theories of "yin-yang," "zang-fu", and "five elements". We assessed the following aspects of the illness: symptomatology; specific location of myofascial trigger points (MTrPs); onset, cause, duration and frequency of symptoms; and patient and family history. The patients tongues, lips, skin colors, and tones of speech were examined. Patients were questioned on various aspects related to breathing, sweating, sleep quality, emotions, and preferences related to color, food, flavors, and weather or seasons. Thirst, gastrointestinal dysfunction, excreta (feces and urine), menstrual cycle, the five senses, and characteristic pain symptoms related to headache, musculoskeletal pain, abdomen, and chest were also investigated. RESULTS: Patients were between 22 and 56 years old, and most were married (78%), possessed a elementary school (66%), and had one or two children (76%). The mean body mass index and body fat were 26.86 kg/ cm2 (range: 17.7 - 39.0) and 32.4% (range: 10.7 - 45.7), respectively. A large majority of women (96%) exhibited alterations in the kidney meridian, and 98% had an altered gallbladder meridian. We observed major changes in the kidney and the gallbladder Qi meridians in 76% and 62% of patients, respectively. Five of the twelve meridians analyzed exhibited Qi patterns similar to pelvic innervation Qi and meridians, indicating that the paths of some of these meridians were directly related to innervation of the pelvic floor and abdominal region. CONCLUSION: The women in this study showed changes in the behavior of the energy meridians, and the paths of some of the meridians were directly related to innervation of the pelvic floor and abdominal region. PMID- 26998388 TI - Intravenous Toxicity Study of Water-soluble Ginseng Pharmacopuncture in SD Rats. AB - OBJECTIVES: Radix Ginseng has been used for thousands of years to treat a wide variety of diseases. Radix ginseng has also been used as a traditional medicine for boosting Qi energy and tonifying the spleen and lungs. Traditionally, its effect could be obtained orally. Nowadays, a new method, the injection of herbal medicine, is being used. This study was performed to investigate the single-dose intravenous toxicity of water-soluble ginseng pharmacopuncture (WSGP) in Sprague Dawley (SD) rats. METHODS: All experiments were carried out at Biotoxtech, an institute authorized to perform non-clinical studies under the regulation of Good Laboratory Practice (GLP). At the age of six weeks, 40 SD rats, 20 male rats and 20 female rats, were allocated into one of 4 groups according to the dosages they would receive. The WSGP was prepared in the Korean Pharmacopuncture Institute under the regulation of Korea-Good Manufacturing Practice (K-GMP). Dosages of WSGP were 0.1, 0.5 and 1.0 mL/animal for the experimental groups, and normal saline was administered to the control group. The rat's general conditions and body weights, the results of their hematological and biochemistry tests, and their necropsy and histopathological findings were investigated to identify the toxicological effect of WSGP injected intravenously. The effect was examined for 14 days after the WSGP injection. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech. RESULTS: No deaths were found in this single-dose toxicity test on the intravenous injection of WSGP, and no significant changes in the rat's general conditions and body weights, the results on their hematological and biochemistry test, and their necropsy findings were observed during the test. The local area of the injection site showed minial change. The lethal dose was assumed to be over 1.0 mL/animal in both sexes. CONCLUSION: These results indicate that WSGP is safe at dosages up to 1 mL/animal. PMID- 26998389 TI - A 4-week Repeated dose Oral Toxicity Study of Mecasin in Sprague-Dawley Rats to Determine the Appropriate Doses for a 13-week, Repeated Toxicity Test. AB - OBJECTIVES: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. METHODS: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/ kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. CONCLUSION: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively. PMID- 26998390 TI - Intramuscular Single-dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats. AB - OBJECTIVES: Bufonis venonum (BV) is the dried white secretions of the auricular and skin glands of the toads Bufo bufo gargarizans or Bufo melanosticus Schneider. This study was performed to evaluate the toxicity of intramuscularly- administered Bufonis venonum pharmacopuncture (BVP) and to calculate its approximate lethality through a single-dose test with Sprague-Dawley (SD) rats. METHODS: Twenty male and 20 female 6-week-old SD rats were injected intramuscularly with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline at 0.5 mL/animal, the low-dosage group injected with 0.125 mL/animal of BVP, the medium-dosage group injected with 0.25 mL/animal of BVP and the high-dosage group injected with 0.5 mL/animal of BVP. All injections were in the left thighs of the rats. After administration, we conducted clinical observations everyday and body weight measurements on days 3, 7 and 14 after the injection. We also carried out hematology, serum biochemistry, and histological observations on day 15 after treatment. RESULTS: No mortalities were observed in any experimental group. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intramuscular injection of BVP were observed in any experimental group. CONCLUSION: Lethal dose of BVP administered via intramuscular injection in SD rats is over 0.5 mL/animal. PMID- 26998391 TI - Systemic Immediate Hypersensitive Reactions after Treatment with Sweet Bee Venom: A Case Report. AB - OBJECTIVES: A previous study showed that bee venom (BV) could cause anaphylaxis or other hypersensitivity reactions. Although hypersensitivity reactions due to sweet bee venom (SBV) have been reported, SBV has been reported to be associated with significantly reduced sensitization compared to BV. Although no systemic immediate hypersensitive response accompanied by abnormal vital signs has been reported with respect to SBV, we report a systemic immediate hypersensitive response that we experienced while trying to use SBV clinically. METHODS: The patient had undergone BV treatment several times at other Oriental medicine clinics and had experienced no adverse reactions. She came to acupuncture & moxibustion department at Semyung university hospital of Oriental medicine (Je cheon, Korea) complaining of facial hypoesthesia and was treated using SBV injections, her first SBV treatment. SBV, 0.05 cc, was injected at each of 8 acupoints, for a total of 0.40 cc: Jichang (ST4), Daeyeong (ST5), Hyeopgeo (ST6), Hagwan (ST7), Yepung (TE17), Imun (TE21), Cheonghoe (GB2), and Gwallyeo (SI18). RESULTS: The patient showed systemic immediate hypersensitive reactions. The main symptoms were abdominal pain, nausea and perspiration, but common symptoms associated with hypersensitivity, such as edema, were mild. Abdominal pain was the most long-lasting symptom and was accompanied by nausea. Her body temperature decreased due to sweating. Her diastolic blood pressure could not be measured on three occasions. She remained alert, though the symptoms persisted. The following treatments were conducted in sequence; intramuscular epinephrine, 1 mg/mL, injection, intramuscular dexamethasone, 5 mg/mL, injection, intramuscular buscopan, 20 mg/mL, injection, oxygen (O2) inhalation therapy, 1 L/minutes, via a nasal prong, and intravascular injection of normal saline, 1 L. After 12 hours of treatment, the symptoms had completely disappeared. CONCLUSION: This case shows that the use of SBV does not completely eliminate the possibility of hypersensitivity and that patients who received BV treatment before may also be sensitized to SBV. Thus, a skin test should be given prior to using SBV. PMID- 26998392 TI - Erratum: A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats. AB - [This corrects the article DOI: 10.3831/KPI.2015.18.026.]. PMID- 26998393 TI - Reprogram to pluripotency: a new logic and a chemical cocktail. AB - Somatic cells from animals and humans can be reprogrammed into pluripotent stem cells by pluripotency factors. Hongkui Deng and colleagues discovered that pluripotency can also be induced with exogenous lineage specifiers via balancing competing differentiation forces. In a related study they achieved, for the first time, restoration of pluripotency in adult somatic cells using a chemical cocktail alone. PMID- 26998395 TI - Announcing a New Open Access Journal: Cell Medicine, Part B of Cell Transplantation. PMID- 26998394 TI - Prescription Opioids in Pregnancy and Birth Outcomes: A Review of the Literature. AB - Prescription opioids are used prenatally for the management of pain, as well as for opiate dependency. Opioids are known to cross the placenta and despite the evidence of possible adverse effects on fetal development, studies have consistently shown prescription opioids are among the most commonly prescribed medications and the prevalence of use is increasing among pregnant women. This article summarizes the available literature documenting potential harms associated with prescription opioid use during pregnancy, including poor fetal growth, preterm birth, birth defects, and neonatal abstinence syndrome. PMID- 26998396 TI - New Strategies for Acute Liver Failure: Focus on Xenotransplantation Therapy. AB - Acute liver failure (ALF) has a poor prognosis and, despite intensive care support, reported average survival is only 10-40%. The most common causes responsible for ALF are viral hepatitis (mainly hepatitis A and B) and acetaminophen poisoning. Hepatic transplantation is the only appropriate treatment for patients with unlikely survival with supportive care alone. Survival rates after transplantation can be as high as 80-90% at the end of the first year. However, there is a shortage of donors and is not uncommon that no appropriate donor matches with the patient in time to avoid death. Therefore, new technologies are in constant development, including blood purification therapies as plasmapheresis, hemodiafiltration, and bioartificial liver support. However, they are still of limited efficacy or at an experimental level, and new strategies are welcome. Accordingly, cell transplantation has been developed to serve as a possible bridge to spontaneous recovery or liver transplantation. Xenotransplant of adult hepatocytes offers an interesting alternative. Moreover, the development of transgenic pigs with less immunogenic cells associated with new immunosuppressor strategies has allowed the development of this area. This article reviews some of the newly developed techniques, with focus on xenotransplant of adult hepatocytes, which might have clinical benefits as future treatment for ALF. PMID- 26998397 TI - Liver Cell Culture Devices. AB - In the last 15 years many different liver cell culture devices, consisting of functional liver cells and artificial materials, have been developed. They have been devised for numerous different applications, such as temporary organ replacement (a bridge to liver transplantation or native liver regeneration) and as in vitro screening systems in the early stages of the drug development process, like assessing hepatotoxicity, hepatic drug metabolism, and induction/inhibition studies. Relevant literature is summarized about artificial human liver cell culture systems by scrutinizing PubMed from 2003 to 2009. Existing devices are divided in 2D configurations (e.g., static monolayer, sandwich, perfused cells, and flat plate) and 3D configurations (e.g., liver slices, spheroids, and different types of bioreactors). The essential features of an ideal liver cell culture system are discussed: different types of scaffolds, oxygenation systems, extracellular matrixes (natural and artificial), cocultures with nonparenchymal cells, and the role of shear stress problems. Finally, miniaturization and high-throughput systems are discussed. All these factors contribute in their own way to the viability and functionality of liver cells in culture. Depending on the aim for which they are designed, several good systems are available for predicting hepatotoxicity and hepatic metabolism within the general population. To predict hepatotoxicity in individual cases genomic analysis might be essential as well. PMID- 26998398 TI - Prospects for Induced Phiripotent Stem Cell-Derived Hepatocytes in Cell Therapy. AB - Induced pluripotent stem (iPS) cells, first established in 2006, have the same characteristics of self-renew-ability and pluripotency as embryonic stem (ES) cells. iPS cells are inducible from patient-specific somatic cells; therefore, they hold significant advantages for overcoming immunological rejection as well as the ethical issues associated with the derivation of ES cells from embryos. Generation of patient-derived hepatocytes by iPS technology and their use in cell transplantation therapy for patients with liver disease is quite attractive. Here, we discuss recent advances and challenges in hepatocyte differentiation from iPS cells and their utility in cell therapy. PMID- 26998400 TI - Upregulation of Adipogenesis and Chondrogenesis in MSC Serum-Free Culture. AB - Serum-free media have been shown to be effective in the expansion of mesenchymal stem cells (MSCs). However, the effects may go beyond cell expansion as the differentiation potentials of the cells may be modified, thus influencing their efficacy for downstream applications. The latter is poorly understood, and this has prompted an evaluation of the influence of a serum-free formulation on the chondrogenic, adipogenic, and osteogenic potential of MSCs. The media consisted of KnockoutTM Serum Replacement (KSR) with a cocktail of growth factors coupled with either collagen or fibronectin coatings. Collagen coating was selected as it promoted consistent cellular attachment. When compared against fetal bovine serum (FBS) controls, cell proliferation in the serum-free media was enhanced at passage 1. Similar levels of surface markers were observed in the two groups with a slight reduction in CD90 and CD73 in the serum-free culture at passage 3. The cultures were screened under differentiation conditions and a better maintenance of the chondrogenic potential was noted in the serum-free media with higher expressions of glycoaminoglycans (GAGs) and collagen II. Chondrogenesis was deficient in the FBS group and this was attributed to the inherent inconsistency of animal serum. Adipogenesis was enhanced in the serum-free group with a higher PPARG expression and lipid accumulation. Similar levels of osteogenic mineralization was noted in the FBS and serum-free groups but collagen I gene expression was suppressed in the latter. This was initially observed during expansion. These observations were attributed to the signaling cascades triggered by the cytokines presented in the serum-free formulation and the interaction with the collagen substrate. The serum-free media helps to maintain and enhance the chondrogenic and adipogenic potentials of the MSCs, respectively. This advantage can be exploited for therapeutic applications in cartilage and adipose tissue engineering. PMID- 26998399 TI - Management of Liver Failure: From Transplantation to Cell-Based Therapy. AB - The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiological role of endogenous stem cells in liver regeneration and on the therapeutic benefits of exogenous stem cell administration with specific emphasis on the potential clinical uses of mesenchymal stem cells. Moreover, critical points that still need clarification, such as the exact identity of the stem-like cell population exerting the beneficial effects, as well as the limitations of stem cell-based therapies, are discussed. PMID- 26998402 TI - Early Immunomodulation by Intravenously Transplanted Mesenchymal Stem Cells Promotes Functional Recovery in Spinal Cord Injured Rats. AB - Although intravenous administration of mesenchymal stem cells (MSCs) can enhance functional recovery after spinal cord injury (SCI), the underlying mechanisms have to be elucidated. In this study, we explored the mechanisms for functional recovery in SCI rats after intravenous transplantation of MSCs derived from human umbilical cord blood. Sprague-Dawley rats were randomly assigned to receive either MSCs (1 * 10(6) cells/0.5 ml) or PBS into the tail vein immediately after SCI. They were then evaluated by the Basso-Beattie-Bresnahan (BBB) locomotor rating scale weekly for 8 weeks and by somatosensory evoked potentials (SSEPs) 8 weeks after transplantation. MSC-treated rats showed a modest but significant improvement in BBB scores and latencies of SSEPs, compared with PBS controls. When human-specific Alu element was measured in the spinal cord, it was detected only 1 h after transplantation, suggesting transient engraftment of MSCs. Inflammatory cytokines were also determined using RT-PCR or Western blot in spinal cord extracts. In MSC-treated rats, the level of proinflammatory cytokine IL-1beta was decreased, but that of anti-inflammatory cytokine IL-10 was increased. MSCs also immediately suppressed IL-6 at 1 h posttransplantation. However, the response of IL-6, which has an immunoregulatory role, was increased 1-3 days after transplantation. In addition, we quantified microglia/macrophage stained with Iba-1 around the damaged spinal cord using immunohistochemistry. A proportion of activated microglia and macrophages in total Iba-1(+) cells was significantly decreased in MSC-treated rats, compared with PBS controls. These results suggest that early immunomodulation by intravenously transplanted MSCs is a potential underlying mechanism for functional recovery after SCI. PMID- 26998401 TI - Mesenchymal Stromal Cells as a Therapeutic Strategy to Support Islet Transplantation in Type 1 Diabetes Mellitus. AB - Type 1 diabetes is an autoimmune disorder that leads to destruction of pancreatic beta islet cells and is a growing global health issue. While insulin replacement remains the standard therapy for type 1 diabetes, exogenous insulin does not mimic the physiology of insulin secretion. Transplantation of pancreatic islets has the potential to cure this disease; however, there are several major limitations to widespread implementation of islet transplants. The use of mesenchymal stromal cells (MSCs) in the treatment of type 1 diabetes has been investigated as an adjunct therapy during islet graft administration to prevent initial islet loss and promote engraftment and revascularization of islets. In this review we will discuss the results of recent MSC studies in animal models of diabetes with a focus on islet transplantation and explore the potential for these findings to be extended to clinical use for the treatment of type 1 diabetes. PMID- 26998404 TI - Knowledge and Perceptions of Health Workers' Training on Ethics, Confidentiality and Medico-Legal Issues. AB - INTRODUCTION: Health care delivery in recent times has become more complicated, as patients expect health personnel to not only provide professional services but be accountable as well. It is thus imperative that health personnel are aware of their responsibility to the patient and also sensitive to medico legal issues if quality health care is to be assured. OBJECTIVE: The aim of the study was to assess the knowledge and perception of health care workers on their training in ethics, confidentiality and medico-legal issues. It was expected that the results would inform policy on the training of the health workers. METHOD: A cross sectional survey was conducted among some categories of health workers (Doctors, Nurses and Health care assistants) at the Accident and Emergency directorate of Komfo Anokye Teaching Hospital, Ghana. A self-administered questionnaire was used to elicit information on ethics, confidentiality and medico- legal issues. Data collected was analyzed using SPSS version 16. RESULTS: A total of 103 health care workers were enrolled on the study representing 96% response rate. The study revealed that 74% had knowledge on ethics, confidentiality and medico- legal concepts; and 35.4% of the respondents indicated that health workers attitudes to ethics, confidentiality and medico- legal concepts was inadequate. About 28.3% indicated that their attitudes were good while 26.3% indicated attitudes were adequate with only 2% indicating that attitudes were very good. Nearly, 49% of the respondents also indicated that training on medico-legal issues should be taught during formal training and also on-the-job. CONCLUSION: Knowledge of health workers on ethics confidentiality and medico-legal issues is high and their perceptions are positive. However, regular training to update their knowledge will be necessary in order to ensure continuous improvement of the quality of health care delivery. PMID- 26998403 TI - Neuroprotective and Angiogenic Effects of Bone Marrow Transplantation Combined With Granulocyte Colony-Stimulating Factor in a Mouse Model of Amyotrophic Lateral Sclerosis. AB - Bone marrow (BM) cells from amyotrophic lateral sclerosis (ALS) patients show significantly reduced expression of several neurotrophic factors. Monotherapy with either wild-type (WT) BM transplantation (BMT) or granulocyte colony stimulating factor (GCSF) has only a small clinical therapeutic effect in an ALS mouse model, due to the phenomenon of neuroprotection. In this study, we investigated the clinical benefits of combination therapy using BMT with WT BM cells, plus GCSF after disease onset in ALS mice [transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) bearing a G93A mutation]. Combined treatment with BMT and GCSF delayed disease progression and prolonged the survival of G93A mice, whereas BMT or GCSF treatment alone did not. Histological study of the ventral horns of lumbar cords from G93A mice treated with BMT and GCSF showed a reduction in motor neuron loss coupled with induced neuronal precursor cell proliferation, increased expression of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor and angiogenin), and neovascularization compared with controls (vehicle only). Compared with G93A microglial cells, most BM-derived WT cells differentiated into microglial cells and strongly expressed neurotrophic factors, combined BMT and GCSF treatment led to the replacement of G93A microglial cells with BM-derived WT cells. These results indicate combined treatment with BMT and GCSF has potential neuroprotective and angiogenic effects in ALS mice, induced by the replacement of G93A microglial cells with BM-derived WT cells. Furthermore, this is the first report showing the effects of combined BMT and GCSF treatment on blood vessels in ALS. PMID- 26998406 TI - Measuring the Photopic Negative Response: Viability of Skin Electrodes and Variability Across Disease Severities in Glaucoma. AB - PURPOSE: The purpose of this study was to determine the feasibility of measuring the photopic negative response (PhNR) of the full-field electroretinogram (ERG) using skin electrodes compared to conjunctival electrodes and its test-retest variability over a range of disease severities in open-angle glaucoma. METHODS: Recordings were performed twice (100 sweeps each) within the same session in 43 eyes of 23 participants with glaucoma to determine its intrinsic variability. The ratio between the PhNR and B-wave amplitude (PhNR/B ratio) was determined for each trace and computed across 5 to 100 sweeps of each recording. Spectral-domain optical coherence tomography was used to measure the average peripapillary retinal nerve fiber layer (RNFL) thickness. RESULTS: The PhNR/B ratio and its magnitude of variability were not significantly different between skin and conjunctival electrodes (P <= 0.197), and the degree of variability decreased substantially with increasing number of sweeps. For skin electrodes, the intraclass correlation coefficient was 0.89 and 0.91 for right and left eyes, respectively. The variability of the PhNR/B ratio decreased with lower RNFL thickness values and larger B-wave amplitudes (P <= 0.002). CONCLUSIONS: Skin electrodes are a viable alternative to conjunctival electrodes when measuring the PhNR in open angle glaucoma, and increasing the number of sweeps substantially reduced its intrinsic variability; the extent of variability was also lower with worsening disease severity. TRANSLATIONAL RELEVANCE: The feasibility of performing ERG recordings widely across a range of disease severities in glaucoma can be achieved through using skin electrodes and increasing the number of sweeps performed to improve measurement repeatability. PMID- 26998405 TI - Enhancement of Visual Field Predictions with Pointwise Exponential Regression (PER) and Pointwise Linear Regression (PLR). AB - PURPOSE: The study was conducted to evaluate threshold smoothing algorithms to enhance prediction of the rates of visual field (VF) worsening in glaucoma. METHODS: We studied 798 patients with primary open-angle glaucoma and 6 or more years of follow-up who underwent 8 or more VF examinations. Thresholds at each VF location for the first 4 years or first half of the follow-up time (whichever was greater) were smoothed with clusters defined by the nearest neighbor (NN), Garway Heath, Glaucoma Hemifield Test (GHT), and weighting by the correlation of rates at all other VF locations. Thresholds were regressed with a pointwise exponential regression (PER) model and a pointwise linear regression (PLR) model. Smaller root mean square error (RMSE) values of the differences between the observed and the predicted thresholds at last two follow-ups indicated better model predictions. RESULTS: The mean (SD) follow-up times for the smoothing and prediction phase were 5.3 (1.5) and 10.5 (3.9) years. The mean RMSE values for the PER and PLR models were unsmoothed data, 6.09 and 6.55; NN, 3.40 and 3.42; Garway-Heath, 3.47 and 3.48; GHT, 3.57 and 3.74; and correlation of rates, 3.59 and 3.64. CONCLUSIONS: Smoothed VF data predicted better than unsmoothed data. Nearest neighbor provided the best predictions; PER also predicted consistently more accurately than PLR. Smoothing algorithms should be used when forecasting VF results with PER or PLR. TRANSLATIONAL RELEVANCE: The application of smoothing algorithms on VF data can improve forecasting in VF points to assist in treatment decisions. PMID- 26998408 TI - Molecular evidence of Burkholderia pseudomallei genotypes based on geographical distribution. AB - Background. Central intermediary metabolism (CIM) in bacteria is defined as a set of metabolic biochemical reactions within a cell, which is essential for the cell to survive in response to environmental perturbations. The genes associated with CIM are commonly found in both pathogenic and non-pathogenic strains. As these genes are involved in vital metabolic processes of bacteria, we explored the efficiency of the genes in genotypic characterization of Burkholderia pseudomallei isolates, compared with the established pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) schemes. Methods. Nine previously sequenced B. pseudomallei isolates from Malaysia were characterized by PFGE, MLST and CIM genes. The isolates were later compared to the other 39 B. pseudomallei strains, retrieved from GenBank using both MLST and sequence analysis of CIM genes. UniFrac and hierachical clustering analyses were performed using the results generated by both MLST and sequence analysis of CIM genes. Results. Genetic relatedness of nine Malaysian B. pseudomallei isolates and the other 39 strains was investigated. The nine Malaysian isolates were subtyped into six PFGE profiles, four MLST profiles and five sequence types based on CIM genes alignment. All methods demonstrated the clonality of OB and CB as well as CMS and THE. However, PFGE showed less than 70% similarity between a pair of morphology variants, OS and OB. In contrast, OS was identical to the soil isolate, MARAN. To have a better understanding of the genetic diversity of B. pseudomallei worldwide, we further aligned the sequences of genes used in MLST and genes associated with CIM for the nine Malaysian isolates and 39 B. pseudomallei strains from NCBI database. Overall, based on the CIM genes, the strains were subtyped into 33 profiles where majority of the strains from Asian countries were clustered together. On the other hand, MLST resolved the isolates into 31 profiles which formed three clusters. Hierarchical clustering using UniFrac distance suggested that the isolates from Australia were genetically distinct from the Asian isolates. Nevertheless, statistical significant differences were detected between isolates from Malaysia, Thailand and Australia. Discussion. Overall, PFGE showed higher discriminative power in clustering the nine Malaysian B. pseudomallei isolates and indicated its suitability for localized epidemiological study. Compared to MLST, CIM genes showed higher resolution in distinguishing those non-related strains and better clustering of strains from different geographical regions. A closer genetic relatedness of Malaysian isolates with all Asian strains in comparison to Australian strains was observed. This finding was supported by UniFrac analysis which resulted in geographical segregation between Australia and the Asian countries. PMID- 26998409 TI - Species presence frequency and diversity in different patch types along an altitudinal gradient: Larix chinensis Beissn in Qinling Mountains (China). AB - Forest communities are mosaic systems composed of patches classified into four different developmental patch types: gap patch (G), building patch (B), mature patch (M) and degenerate patch (D). To study the mechanisms maintaining diversity in subalpine coniferous forests, species presence frequency and diversity in the four distinct patch types (G, B, M and D) of Larix chinensis conifer forests at three altitudinal gradients in the Qinling Mountains were analyzed. Our results were as follows: (1) Different species (or functional groups) had distinct presence frequencies in the four different patch types along the altitudinal gradient; (2) Some species or functional groups (species groups sharing similar traits and responses to the environment) only occurred in some specific patches. For seed dispersal, species using wind mainly occurred in G and D, while species using small animals mainly occurred in B and M; (3) Species composition of adjacent patch types was more similar than non-adjacent patch types, based on the lower beta diversity index of the former; (4) The maximum numbers of species and two diversity indices (D' and H') were found in the middle altitudes. Various gap forming processes and dispersal limitation may be the two major mechanisms determining species diversity in Larix chinensis coniferous forests at the patch scale. PMID- 26998407 TI - Direct Reprogramming for Pancreatic Beta-Cells Using Key Developmental Genes. AB - Direct reprogramming is a promising approach for regenerative medicine whereby one cell type is directly converted into another without going through a multipotent or pluripotent stage. This reprogramming approach has been extensively explored for the generation of functional insulin-secreting cells from non-beta-cells with the aim of developing novel cell therapies for the treatment of people with diabetes lacking sufficient endogenous beta-cells. A common approach for such conversion studies is the introduction of key regulators that are important in controlling beta-cell development and maintenance. In this review, we will summarize the recent advances in the field of beta-cell reprogramming and discuss the challenges of creating functional and long-lasting beta-cells. PMID- 26998410 TI - Pre- and post-experimental manipulation assessments confirm the increase in number of birds due to the addition of nest boxes. AB - Secondary cavity nesting (SCN) birds breed in holes that they do not excavate themselves. This is possible where there are large trees whose size and age permit the digging of holes by primary excavators and only rarely happens in forest plantations, where we expected a deficit of both breeding holes and SCN species. We assessed whether the availability of tree cavities influenced the number of SCNs in two temperate forest types, and evaluated the change in number of SCNs after adding nest boxes. First, we counted all cavities within each of our 25-m radius sampling points in mature and young forest plots during 2009. We then added nest boxes at standardised locations during 2010 and 2011 and conducted fortnightly bird counts (January-October 2009-2011). In 2011 we added two extra plots of each forest type, where we also conducted bird counts. Prior to adding nest boxes, counts revealed more SCNs in mature than in young forest. Following the addition of nest boxes, the number of SCNs increased significantly in the points with nest boxes in both types of forest. Counts in 2011 confirmed the increase in number of birds due to the addition of nest boxes. Given the likely benefits associated with a richer bird community we propose that, as is routinely done in some countries, forest management programs preserve old tree stumps and add nest boxes to forest plantations in order to increase bird numbers and bird community diversity. PMID- 26998411 TI - Selection of reference genes for RT-qPCR studies in blood of beluga whales (Delphinapterus leucas). AB - Reverse transcription quantitative PCR (RT-qPCR) is used for research in gene expression, and it is vital to choose appropriate housekeeping genes (HKGs) as reference genes to obtain correct results. The purpose of this study is to determine stably expressed HKGs in blood of beluga whales (Delphinapterus leucas) that can be the appropriate reference genes in relative quantification in gene expression research. Sixty blood samples were taken from four beluga whales. Thirteen candidate HKGs (ACTB, B2M, GAPDH, HPRT1, LDHB, PGK1, RPL4, RPL8, RPL18, RPS9, RPS18, TFRC, YWHAZ) were tested using RT-qPCR. The stability values of the HKGs were determined by four different algorithms. Comprehensive analysis of the results revealed that RPL4, PGK1 and ACTB are strongly recommended for use in future RT-qPCR studies in beluga blood samples. This research provides recommendation of reference gene selection, which may contribute to further mRNA relative quantification research in the peripheral blood leukocytes in captive cetaceans. The gene expression assessment of the immune components in blood have the potential to serve as an important approach to evaluating cetacean health influenced by environmental insults. PMID- 26998412 TI - Symmetry-based reciprocity: evolutionary constraints on a proximate mechanism. AB - Background. While the evolution of reciprocal cooperation has attracted an enormous attention, the proximate mechanisms underlying the ability of animals to cooperate reciprocally are comparatively neglected. Symmetry-based reciprocity is a hypothetical proximate mechanism that has been suggested to be widespread among cognitively unsophisticated animals. Methods. We developed two agent-based models of symmetry-based reciprocity (one relying on an arbitrary tag and the other on interindividual proximity) and tested their ability both to reproduce significant emergent features of cooperation in group living animals and to promote the evolution of cooperation. Results. Populations formed by agents adopting symmetry based reciprocity showed differentiated "social relationships" and a positive correlation between cooperation given and received: two common aspects of animal cooperation. However, when reproduction and selection across multiple generations were added to the models, agents adopting symmetry-based reciprocity were outcompeted by selfish agents that never cooperated. Discussion. In order to evolve, hypothetical proximate mechanisms must be able to stand competition from alternative strategies. While the results of our simulations require confirmation using analytical methods, we provisionally suggest symmetry-based reciprocity is to be abandoned as a possible proximate mechanism underlying the ability of animals to reciprocate cooperative interactions. PMID- 26998413 TI - Movement, demographics, and occupancy dynamics of a federally-threatened salamander: evaluating the adequacy of critical habitat. AB - Critical habitat for many species is often limited to occupied localities. For rare and cryptic species, or those lacking sufficient data, occupied habitats may go unrecognized, potentially hindering species recovery. Proposed critical habitat for the aquatic Jollyville Plateau salamander (Eurycea tonkawae) and two sister species were delineated based on the assumption that surface habitat is restricted to springs and excludes intervening stream reaches. To test this assumption, we performed two studies to understand aspects of individual, population, and metapopulation ecology of E. tonkawae. First, we examined movement and population demographics using capture-recapture along a spring influenced stream reach. We then extended our investigation of stream habitat use with a study of occupancy and habitat dynamics in multiple headwater streams. Indications of extensive stream channel use based on capture-recapture results included frequent movements of >15 m, and high juvenile abundance downstream of the spring. Initial occupancy of E. tonkawae was associated with shallow depths, maidenhair fern presence and low temperature variation (indicative of groundwater influence), although many occupied sites were far from known springs. Additionally, previously dry sites were three times more likely to be colonized than wet sites. Our results indicate extensive use of stream habitats, including intermittent ones, by E. tonkawae. These areas may be important for maintaining population connectivity or even as primary habitat patches. Restricting critical habitat to occupied sites will result in a mismatch with actual habitat use, particularly when assumptions of habitat use are untested, thus limiting the potential for recovery. PMID- 26998414 TI - Functional assessment of chronic illness therapy-the fatigue scale exhibits stronger associations with clinical parameters in chronic dialysis patients compared to other fatigue-assessing instruments. AB - Background. Patients with end-stage renal disease (ESRD) have a high symptom burden, among which fatigue is highly prevalent. Many fatigue-assessing instruments exist, but comparisons among instruments in this patient population have yet to be investigated. Methods. ESRD patients under chronic hemodialysis were prospectively enrolled and seven types of fatigue instruments were administered: Brief Fatigue Inventory (BFI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Fatigue Severity Scale (FSS), Lee Fatigue Scale (LFS), Fatigue Questionnaire (FQ), Fatigue Symptom Inventory (FSI), and Short-Form 36-Vitality (SF36-V). Using these instruments, we investigated the correlation between fatigue severity and clinical/biochemical parameters, including demographic/comorbidity profile, dialysis-related complications, and frailty severity. We used regression analysis with serum albumin and frailty severity as the dependent variables to investigate the independent correlations. Results. A total of 46 ESRD patients were enrolled (average age of 67 +/- 11.6 years), and 50% of them had type 2 diabetes mellitus. Results from the seven tested instruments showed high correlation with each other. We found that the fatigue severity by FACIT-F was significantly associated with age (p = 0.03), serum albumin (p = 0.003) and creatinine (p = 0.02) levels, while SF36-V scores were also significantly associated with age (p = 0.02) and serum creatinine levels (p = 0.04). However, the fatigue severity measured by the FSS, FSI, FQ, BFI, and LFS did not exhibit these associations. Moreover, regression analysis showed that only FACIT-F scores were independently associated with serum albumin levels and frailty severity in ESRD patients. Conclusion. Among the seven fatigue assessing instruments, only the FACIT-F yielded results that demonstrated significant and independent associations with important outcome-related features in ESRD patients. PMID- 26998416 TI - Broadening Our Perspectives on Adult Literacy, Numeracy, and Problem-Solving Skills with PIAAC Data: A Commentary on The Centre for Literacy's 2014 Summer Institute. PMID- 26998417 TI - The use of cognitive ability measures as explanatory variables in regression analysis. AB - Cognitive ability measures are often taken as explanatory variables in regression analysis, e.g., as a factor affecting a market outcome such as an individual's wage, or a decision such as an individual's education acquisition. Cognitive ability is a latent construct; its true value is unobserved. Nonetheless, researchers often assume that a test score, constructed via standard psychometric practice from individuals' responses to test items, can be safely used in regression analysis. We examine problems that can arise, and suggest that an alternative approach, a "mixed effects structural equations" (MESE) model, may be more appropriate in many circumstances. PMID- 26998415 TI - Genetics, diagnosis, and future treatment strategies for primary ciliary dyskinesia. AB - INTRODUCTION: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder resulting in chronic oto-sino-pulmonary disease. While PCD is estimated to occur in 1 in 20,000 individuals, fewer than 1,000 patients in the US have a well-established diagnosis. AREAS COVERED: We provide an overview of the clinical manifestations of PCD, describe the evolution of diagnostic methods, and critique the literature on management of PCD. EXPERT OPINION: Although interest in clinical studies in non-CF bronchiectasis has increased in recent years, some of whom enroll patients with PCD, the literature regarding therapy for PCD as a distinct entity is lacking, as the numbers are small, and there have been no sub-analyses published. However, with improved screening and diagnostic methods, the development of clinical and research consortiums, and actively enrolling registries of PCD patients, the environment is conducive to perform longitudinal studies of disease course and therapeutic studies to alter that course. PMID- 26998419 TI - Towards Measuring the Food Quality of Grocery Purchases: an Estimation Model of the Healthy Eating Index-2010 Using only Food Item Counts. AB - Measuring the quality of food consumed by individuals or groups in the U.S. is essential to informed public health surveillance efforts and sound nutrition policymaking. For example, the Healthy Eating Index-2010 (HEI) is an ideal metric to assess the food quality of households, but the traditional methods of collecting the data required to calculate the HEI are expensive and burdensome. We evaluated an alternative source: rather than measuring the quality of the foods consumers eat, we want to estimate the quality of the foods consumers buy. To accomplish that we need a way of estimating the HEI based solely on the count of food items. We developed an estimation model of the HEI, using an augmented set of the What We Eat In America (WWEIA) food categories. Then we mapped ~92,000 grocery food items to it. The model uses an inverse Cumulative Distribution Function sampling technique. Here we describe the model and report reliability metrics based on NHANES data from 2003-2010. PMID- 26998418 TI - Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update. AB - Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds. PMID- 26998420 TI - Ibandronate: The loading dose concept in the treatment of metastatic bone pain. AB - BACKGROUND/AIM: Severe bone pain is experienced by 60-80% of patients with metastatic bone disease, and has a profound impact on quality of life. Therefore, effective pain relief is an important goal in managing metastatic bone disease. Orthopedic surgeons are often challenged with patients presenting with newly diagnosed bone metastases and severe and disabling bone pain. It is important to provide fast and sufficient analgesia. Clinical trials have demonstrated that bisphosphonates reduce effectively and sustained bone pain by approved standard dosage over time. Open label prospective trials have shown that short time high dose i.v. Ibandronate is effective in rapid pain relief in different primary tumors. PATIENTS AND METHODS: In 33 patients with metastatic bone pain from newly diagnosed skeletal metastases we utilized the loading-dose concept for intravenous ibandronate (6 mg infused over 1 h on 3 consecutive days). RESULTS: In 33 patients loading-dose ibandronate therapy significantly reduced bone pain within the first 5-7 days (VAS day 0: 6-8 vs. day 7: 3-4). Only 3 patients showed no response concerning a distinct pain reduction within the first days of therapy. There was no increase in pain medication. CONCLUSION: This clinical observational study in selected patients with severe metastatic bone pain undergoing an intensive high dosed ibandronate-therapy for a short period demonstrated that loading-dose ibandronate (6 mg i.v., 3 consecutive days) resulted in a reduction of pain within days. PMID- 26998421 TI - Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status. AB - Conventional therapy of primary bone tumors includes surgical excision with wide resection, which leads to physical and aesthetic defects. For reconstruction of bone and joints, allografts can be supplemented with mesenchymal stem cells (MSCs). Similarly, adipose tissue transfer (ATT) is supplemented with adipose derived stem cells (ADSCs) to improve the efficient grafting in the correction of soft tissue defects. MSC-like cells may also be used in tumor-targeted cell therapy. However, MSC may have adverse effects on sarcoma development. In the present study, human ADSCs, MSCs and pre-osteoclasts were co-injected with human MNNG-HOS osteosarcoma cells in immunodeficient mice. ADSCs and MSCs, but not the osteoclast precursors, accelerated the local proliferation of MNNG-HOS osteosarcoma cells. However, the osteolysis and the metastasis process were not exacerbated by ADSCs, MSCs, or pre-osteoclasts. In vitro proliferation of MNNG HOS and Saos-2 osteosarcoma cells was increased up to 2-fold in the presence of ADSC-conditioned medium. In contrast, ADSC-conditioned medium did not change the dormant, quiescent state of osteosarcoma cells cultured in oncospheres. Due to the enhancing effect of ADSCs/MSCs on in vivo/in vitro proliferation of osteosarcoma cells, MSCs may not be good candidates for osteosarcoma-targeted cell therapy. Although conditioned medium of ADSCs accelerated the cell cycle of proliferating osteosarcoma cells, it did not change the quiescent state of dormant osteosarcoma cells, indicating that ADSC-secreted factors may not be involved in the risk of local recurrence. PMID- 26998422 TI - A comparative study between limb-salvage and amputation for treating osteosarcoma. AB - PURPOSE: Osteosarcoma is an aggressive malignant neoplasm, and conflicting findings have been reported on the survival and function recovery in osteosarcoma patients experiencing limb salvage or amputation. In the present study, we compared clinical outcomes regarding limb salvage surgery vs. amputation for osteosarcoma patients by a meta-analysis. METHOD: Literature search was conducted in CNKI, Medline, Embase, the Cochrane Database, and Web of Sciences, and the quality of included studies was evaluated based on Newcastle-Ottawa scale quality assessment. Odds ratio and 95% confidence interval of the local recurrence, 5 year overall survival, and metastasis occurrence were calculated. RESULTS: 17 articles were included according to selection criteria. There were 1343 patients in total derived from these studies. Our result showed that there was no significant difference between limb salvage surgery and amputation with respect to local recurrence, and patients with limb salvage surgery had a higher 5-year overall survival, and a lower metastasis occurrence. CONCLUSIONS: The present study provided more comprehensive evidences to support limb salvage surgery as an optimal treatment of osteosarcoma patients. PMID- 26998423 TI - Hypoxia promotes drug resistance in osteosarcoma cells via activating AMP activated protein kinase (AMPK) signaling. AB - PURPOSE: Drug resistance has been recognized to be a major obstacle to the chemotherapy for osteosarcoma. And the potential importance of hypoxia as a target to reverse drug resistance in osteosarcoma has been indicated, though the mechanism underlining such role is not clarified. The present study aims to investigate the role of hypoxia in the drug resistance in osteosarcoma cells via activating AMP-activated protein kinase (AMPK) signaling. EXPERIMENTAL DESIGN: We investigated the promotion of the resistance to doxorubicin of osteosarcoma MG-63 and U2-os cells in vitro, and then determined the role of hypoxia-inducible factor-1 (HIF-1)alpha and HIF-1beta, the activation and regulatory role of AMPK in the osteosarcoma U2-os cells which were treated with doxorubicin under hypoxia. RESULTS: It was demonstrated that hypoxia significantly reduced the sensitivity of MG-63 and U2-os cells to doxorubicin, indicating an inhibited viability reduction and a reduced apoptosis promotion. And such reduced sensitivity was not associated with HIF-1alpha, though it was promoted by hypoxia in U2-os cells. Interestingly, the AMPK signaling was significantly promoted by hypoxia in the doxorubicin-treated U2-os cells, with a marked upregulation of phosphorylated AMPK (Thr 172) and phosphorylated acetyl-CoA carboxylase (ACC) (Ser 79), which were sensitive to the AMPK activator, AICAR and the AMPK inhibitor, Compound C. Moreover, the promoted AMPK activity by AICAR or the downregulated AMPK activity by Compound C significantly reduced or promoted the sensitivity of U2-os cells to doxorubicin. CONCLUSION: The present study confirmed the AMPK signaling activation in the doxorubicin-treated osteosarcoma cells, in response to hypoxia, and the chemical upregulation or downregulation of AMPK signaling reduced or increased the chemo-sensitivity of osteosarcoma U2-os cells in vitro. Our study implies that AMPK inhibition might be a effective strategy to sensitize osteocarcoma cells to chemotherapy. PMID- 26998425 TI - The epidemiological and clinical features of primary giant cell tumor around the knee: A report from the multicenter retrospective study in china. AB - OBJECTIVES: We aimed to determine the demographic characteristics of giant cell tumor around the knee in China. METHODS: Between March 2000 and June 2014, patients with primary giant cell tumor around the knee were recruited from 6 institutions located in different regions of China, and were reviewed retrospectively the clinical features according to gender and age. RESULTS: 334 qualified patients were included in this study. The sex ratio was 1.14:1 (178/156), with mean ages of 36.9 years in men and 33.1 years in women, constituting a significant difference (P=0.007). The prevalence of pathological fracture was 32.9% overall (28.7% in men and 37.8% in women). The prevalence of simple fracture was significantly higher in women (26.3%) than in men (15.2%), P=0.042. Tumor location and staging did not differ significantly according to sex (P>0.05). However, comparing with >40 years old, those patients aged <=40 were more likely to have a right knee tumor (56.7% vs. 44.7%, P=0.042), less likely to have Enneking stage 3 disease (18.6% vs. 35.0%, P=0.005), and less likely to have both soft-tissue extension and a mass (18.6% vs. 34.0%, P=0.009). CONCLUSIONS: Giant cell tumor around the knee was more common in men than in women, although female patients were younger on average. Further, cases among patients <=40 years old were observed to be milder than cases among older patients. The results suggest that efficient treatment and preservation of function should both be valued for young patients with giant cell tumor around the knee. PMID- 26998426 TI - Goserelin, as an ovarian protector during (neo)adjuvant breast cancer chemotherapy, prevents long term altered bone turnover. AB - BACKGROUND: The Ovarian Protection Trial In Premenopausal Breast Cancer Patients "OPTION" trial (NCT00427245) was a prospective, multicenter, randomised, open label study evaluating the frequency of primary ovarian insufficiency (POI) at 12 months in women randomised to 6-8 cycles of (neo)adjuvant chemotherapy (CT) +/- goserelin (G). Here we report the results of a secondary endpoint analysis of the effects of CT+/-G on markers of bone turnover. METHODS: Serum for bone alkaline phosphatase (BALP) and urine for N-terminal telopeptide (NTX) were collected at baseline, 6, 12, 18, 24 and 36 months. Changes in median levels of bone turnover markers were evaluated for the overall population, according to age stratification at randomisation (<=40 vs >40 years) and with exploratory analysis according to POI rates at 12 months. RESULTS: In the overall population, there was a significant increase in NTX at 6 months compared to baseline in patients treated with CT+G (40.81 vs 57.82 p=0.0074) with normalisation of levels thereafter. BALP was significantly increased compared to baseline at 6 months and 12 months in those receiving CT+G, but normalised thereafter. BALP remained significantly higher compared to baseline at 12, 24 and 36 months in patients receiving CT, resulting in a significant difference between treatment groups at 36 months (CT+G 5.845 vs CT 8.5 p=0.0006). These changes were predominantly seen in women >40 years. Women with POI at 12 months showed altered bone formation compared to baseline levels for a longer duration than women who maintained menses. CONCLUSION: Addition of G to CT increases bone turnover during treatment with normalisation after cessation of treatment suggesting G may offer sufficient ovarian protection against CT induced POI to negate longstanding altered bone turnover associated with POI. PMID- 26998424 TI - P62: An emerging oncotarget for osteolytic metastasis. AB - Bone metastasis occurs in the majority of late-stage tumors with poor prognosis. It is mainly classified as osteoblastic metastasis and osteolytic metastasis. The pathogenesis of osteolytic metastasis is a "vicious cycle" between tumor cells and bone cells (primarily the osteoclasts), which is mediated by secretory factors. The P62 adapter protein is a versatile multitasker between tumor cells and bone cells. The overexpression of P62 has been detected among a variety of tumors, playing positive roles in both tumorigenesis and metastasis. Moreover, P62 is an important modulator of the osteoclastogenesis pathway. Therefore, the ability of P62 to modulate tumors and osteoclasts suggests that it may be a feasible oncotarget for bone metastasis, especially for osteolytic metastasis. Recent research has shown that a P62 DNA vaccine triggered effective anti-tumor, anti-metastatic and anti-osteoporotic activities. Growing lines of evidence point to P62 as an emerging oncotarget for osteolytic metastasis. In this review, we outline the different roles of P62 in tumor cells and osteoclasts, focusing on the P62-related signaling pathway in key steps of osteolytic metastasis, including tumorigenesis, metastasis and osteoclastogenesis. Finally, we discuss the newest observations on P62 as an oncotarget for osteolytic metastasis treatment. PMID- 26998428 TI - Drug resistance in malaria: A predicament. PMID- 26998429 TI - Leishmaniasis: Path toward elimination from the Indian subcontinent. PMID- 26998430 TI - Utilitarian and deontological ethics in medicine. AB - Medical ethics is a sensible branch of moral philosophy and deals with conflicts in obligations/duties and their potential outcome. Two strands of thought exist in ethics regarding decision-making: deontological and utilitarian. In deontological approach, outcomes/consequences may not just justify the means to achieve it while in utilitarian approach; outcomes determine the means and greatest benefit expected for the greatest number. In brief, deontology is patient-centered, whereas utilitarianism is society-centered. Although these approaches contradict each other, each of them has their own substantiating advantages and disadvantages in medical practice. Over years, a trend has been observed from deontological practice to utilitarian approach leading to frustration and discontentment. Health care system and practitioners need to balance both these ethical arms to bring congruity in medical practice. PMID- 26998427 TI - Hermes (Rbpms) is a Critical Component of RNP Complexes that Sequester Germline RNAs during Oogenesis. AB - The germ cell lineage in Xenopus is specified by the inheritance of germ plasm that assembles within the mitochondrial cloud or Balbiani body in stage I oocytes. Specific RNAs, such as nanos1, localize to the germ plasm. nanos1 has the essential germline function of blocking somatic gene expression and thus preventing Primordial Germ Cell (PGC) loss and sterility. Hermes/Rbpms protein and nanos RNA co-localize within germinal granules, diagnostic electron dense particles found within the germ plasm. Previous work indicates that nanos accumulates within the germ plasm through a diffusion/entrapment mechanism. Here we show that Hermes/Rbpms interacts with nanos through sequence specific RNA localization signals found in the nanos-3'UTR. Importantly, Hermes/Rbpms specifically binds nanos, but not Vg1 RNA in the nucleus of stage I oocytes. In vitro binding data show that Hermes/Rbpms requires additional factors that are present in stage I oocytes in order to bind nanos1. One such factor may be hnRNP I, identified in a yeast-2-hybrid screen as directly interacting with Hermes/Rbpms. We suggest that Hermes/Rbpms functions as part of a RNP complex in the nucleus that facilitates selection of germline RNAs for germ plasm localization. We propose that Hermes/Rbpms is required for nanos RNA to form within the germinal granules and in this way, participates in the germline specific translational repression and sequestration of nanos RNA. PMID- 26998431 TI - Systematic review on Endolimax nana: A less well studied intestinal ameba. AB - Of the so-called nonpathogenic intestinal protozoa, Endolimax nana belongs to the ones least well described. Most data on E. nana have emerged from general surveys of intestinal parasites in selected cohorts and mostly in the absence of any particular focus on Endolimax. Hence, the genus of Endolimax remains largely unexplored in terms of morphology, taxonomy, genetic diversity, host specificity, and epidemiology. In this review, we seek to provide an overview of the work that has been performed on the parasite since the genus Endolimax was described by Kuenen and Swellengrebel in 1917 and suggest activities that may pave the way for a better understanding of E. nana in a clinical and public health context. PMID- 26998432 TI - Antimalarial drug resistance: An overview. AB - Malaria is a major public health burden throughout the world. Resistance to the antimalarial drugs has increased the mortality and morbidity rate that is achieved so far through the malaria control program. Monitoring the drug resistance to the available antimalarial drugs helps to implement effective drug policy, through the in vivo efficacy studies, in vitro drug susceptibility tests and detection of molecular markers. It is important to understand the mechanism of the antimalarial drugs, as it is one of the key factors in the emergence and spread of drug resistance. This review summarizes the commonly used antimalarial drugs, their mechanism of action and the genetic markers validated so far for the detection of drug-resistant parasites. PMID- 26998433 TI - Polymerase chain reaction detection and inducible nitric-oxide synthase expression of Leishmania major in mice inoculated by two different routes. AB - INTRODUCTION: Leishmania major needs a sensitive and specific method for proper diagnosis. This study aims to study the course and histopathology of L. major in certain tissues of experimentally infected BALB/c mice after subcutaneous (sc) and intraperitoneal (ip) inoculation. MATERIALS AND METHODS: After infecting BALB/c mice using sc and ip inoculation, the histopathology was studied. The kinetoplastic DNA polymerase chain reaction (PCR) for its molecular detection and detect the inducible nitric-oxide synthase (iNOS) pattern during the first 3 months of infection. RESULT: PCR could detect the presence of L. major in all spleens, lymph nodes, and skin ulcers by both inoculation routes while (33%) and (42%) of livers were positive after sc and ip routes, respectively. Chronic inflammatory cell infiltrates with capsulitis was found in the spleen, lymph nodes, and liver. Granulomas were found in the spleen and liver. There was a statistically significant difference in iNOS expression along the experiment in the spleen and lymph nodes by both routes and in the liver by ip only. Apart from the liver, iNOS could not be detected on the 2(nd) week postinfection and was high after 1 month for both routes in all samples; a moderate decrease at 2 months and the highest decrease were detected after 3 months. CONCLUSIONS: L. major inoculation by both routes produce visceral disease in mice, and kinetoplastic DNA PCR can detect its presence from the 2(nd) week up to the 3(rd) month postinfection. The iNOS expression was high at 1 and 2 months and remained throughout the 3 months of the experiment; which plays an important role in the disease course and control. PMID- 26998434 TI - Topographic congruence of calcified parenchymal neurocysticercosis and other structural brain lesions with epileptiform activity. AB - INTRODUCTION: Calcified parenchymal neurocysticercosis (NCC) lesions are commonly detected in many individuals with refractory epilepsy. However, the relationship between these lesions and epilepsy is not fully determined. We sought to determine if calcified parenchymal NCC demonstrated topographic congruence with epileptiform activity in refractory epilepsy patients. Additional patients with other structural brain lesions were included for comparison. SUBJECTS AND METHODS: Retrospective cross-sectional analysis of all patients treated at a community-based neurology clinic for refractory epilepsy during a 3-month period and with structural brain lesions detected by neuroimaging studies. RESULTS: A total of 105 patients were included in the study, including 63 with calcified parenchymal NCC lesions and 42 with other structural brain lesions. No significant relationship was detected between hemispheric localization of calcified parenchymal NCC lesions and epileptiform activity. For those with other structural brain lesions, the hemispheric localization was significantly related to the side of epileptiform activity (Chi-square = 11.13, P = 0.025). In addition, logistic regression models showed that those with right-sided non-NCC lesions were more likely to have right-sided epileptiform activity (odds ratio = 4.36, 95% confidence interval [CI] =1.16-16.31, P = 0.029), and those with left sided non-NCC lesions were more likely to have left-sided epileptiform activity (odds ratio = 7.60, 95% CI = 1.89-30.49, P = 0.004). CONCLUSION: The lack of correlation between the side of calcified parenchymal NCC lesions and the side of the epileptiform activity suggests that these lesions may be incidental findings in many patients. PMID- 26998435 TI - Hepatic visceral larva migrans, a resilient entity on imaging: Experience from a tertiary liver center. AB - INTRODUCTION: Hepatic visceral larva migrans (VLM) is an uncommon parasitic manifestation seen in the liver. It presents as coalescing, conglomerated, or solitary abscess cavities in the liver on imaging. We conducted a retrospective clinico-radiological analysis of 24 patients with biopsy proven VLM who were reviewed and followed up at our tertiary liver institute over a period of 4 years. MATERIALS AND METHODS: The study was performed to correlate the radiological features and imaging response to therapy for hepatic VLM. The disease course, imaging findings, progressive, absolute eosinophil counts (AEC), hydatid serology, and the extent of radiological regression of the liver lesions, on follow-up were analyzed. RESULTS: Imaging showed a diagnostic accuracy of 42%. Hydatid serology was positive in 46% patients before starting treatment. The median pretreatment AEC of 507 showed a significant posttreatment AEC decline to median value of 117. The Wilcoxon signed ranks test showed significant decline in the AEC (P < 0.001). Radiological regression was present in all lesions. However, patients showed residual abscesses on imaging, up to 2 years on follow-up. CONCLUSION: This study reveals that AEC has a significant predictive value in diagnosis and as a marker for disease regression. Complete radiological resolution of hepatic lesions does not correlate with total clinical remission. This finding warrants the need for further studies to look into the role of prolonged medical therapy or surgery as an alternate to current therapy module in cases of hepatic visceral larva abscesses. PMID- 26998437 TI - Seroprevalence of Entamoeba histolytica from a tertiary care hospital, South India. AB - INTRODUCTION: Amebiasis is the third leading cause of death after malaria and schistosomiasis. Diagnosis is based on microscopy, culture, isoenzyme analysis, and serology-based techniques. In resource-limited nation such as India where polymerase chain reaction cannot be employed, serology is considered to be the reliable diagnostic tool. To find the seroprevalence of Entamoeba histolytica IgG antibody by enzyme-linked immunosorbent assay (ELISA) among the liver abscess cases and healthy controls. MATERIALS AND METHODS: Commercially available RIDASCREEN Entamoeba IgG ELISA kit was used to evaluate the samples as per manufacturer's instruction. RESULTS: A total of 322 samples were evaluated by ELISA. 94/157 (59.87%) were positive for amebic liver abscess cases, 2/13 (15.38%) were positive in suspected amebiasis group, 5/15 (33.3%) were positive in nonamoebic hepatic disorder group, 5/39 (12.8%) were positive in other parasitic disorders, and 2/98 (2.04%) were positive in presumed healthy controls. The sensitivity and specificity of the assay were found to be 56% and 92%, respectively. CONCLUSION: In an endemic nation such as India and other developing countries, ELISA can be used as a routine surveillance test in a clinical setup to detect amoebiasis if the cases are judicially evaluated along with the other routine tests. PMID- 26998436 TI - Detection of chloroquine and artemisinin resistance molecular markers in Plasmodium falciparum: A hospital based study. AB - INTRODUCTION: Emergence of chloroquine (CQ) resistance in Plasmodium falciparum has increased the morbidity and mortality of falciparum malaria worldwide. Artemisinin-based combination therapies are now recommended by the World Health Organization as the first line treatment for falciparum malaria. Numerous molecular markers have been implicated in the CQ and artemisinin resistance. MATERIALS AND METHODS: A total of 26 confirmed cases of falciparum malaria (by giemsa stained thick and thin smear, quantitative buffy coat, immunochromatographic test, or polymerase chain reaction [PCR]) were included in the study. About 5 ml of ethylenediaminetetraacetic acid blood sample was collected and stored at -20 degrees C till use. Plasmodium DNA was extracted using QIAamp whole blood DNA extraction kit. PCR was done to amplify pfcrt, pfmdr1, pfserca, and pfmrp1 genes and the amplicons obtained were sequenced by Macrogen, Inc., Korea. Single nucleotide polymorphism (SNP) analysis was done using Bio-Edit Sequence Alignment Editor. RESULTS: Out of the four genes targeted, we noted a SNP in the pfcrt gene alone. This SNP (G > T) was noted in the 658(th) position of the gene, which was seen in 13 patients. The pfmdr1 and pfserca genes were present in 9 and 14 patients respectively. But we could not find any SNPs in these genes. This SNP in pfcrt gene was not significantly associated with any adverse outcome and neither altered disease progression. CONCLUSION: Presence of a single SNP may not be associated with any adverse clinical outcome. As the sample size was small, we may have not been able to detect any other known or unknown polymorphisms. PMID- 26998439 TI - Decreased response to artemisinin combination therapy in falciparum malaria: A preliminary report from South India. PMID- 26998438 TI - A case report of an uncommon parasitic infection of human balantidiasis. AB - Balantidium coli, a large, ciliated pathogen, is known to cause balantidiasis in humans. We report a case of B. coli infection in a 37-year-old male with tuberculosis and presenting with fever, anorexia, mild abdominal pain, and episodes of loose stools for 1 week. PMID- 26998440 TI - Phenazopyridine as an innovative stain for permanent staining of trematodes. PMID- 26998442 TI - An E-mail interview with Prof. Shin-ichiro Kawazu. PMID- 26998441 TI - Central nervous system infection due to Acanthamoeba: A case series. PMID- 26998445 TI - Managing children with diabetes within the family: Entering into the Diabetes Orbit. AB - BACKGROUND: Diabetes is the disease of family and parents of children with diabetes face different problems which concerns meeting the developmental needs of children and daily control of children with diabetes. This article aims to explain how to manage diabetes around the child's life within the family. METHODS: In this qualitative study, data was collected through semi-structured interview technique and was analyzed using Grounded Theory approach. The process of data collection was carried out by purposeful sampling. The participants included 13 individuals from nine families (11 parents and two children with diabetes). The research environment was health centers in Iran providing care to the families of children with diabetes. Data analysis was performed using Corbin and Strauss approach. Data was analyzed with using MAXQDA software (version 10). RESULTS: The core category of "Entering into the Orbit of Diabetes" addresses the story of how to keep track of managing children with diabetes within the family which included Main categories "bitter taste of sugar", "drawing coordinates of diabetes", and "taking control of diabetes". CONCLUSION: The outcome of "enter into the orbit of diabetes" results capturing the control of diabetes. The findings of the present study may play an integral part to help households with practicing appropriate strategies for the management of children with diabetes. PMID- 26998444 TI - Does this patient have Pheochromocytoma? a systematic review of clinical signs and symptoms. AB - CONTEXT: Pheochromocytoma is a rare disease but with high mortality if it is not being diagnosed early. Several biochemical tests with high accuracy have been obtained, but the clinical threshold for request of these tests is not determined clearly. OBJECTIVES: To determine the Likelihood Ratios of clinical symptoms and signs in diagnosing pheochromocytoma. And also meta-analysis of their sensitivity in this disease. DATA SOURCES: MEDLINE was searched for relevant English-language articles dated 1960 to February 2014. Bibliographies were searched to find additional articles. STUDY SELECTION: We included original studies describing the sensitivity and/or likelihood ratios of signs and symptoms in clinical suspicion of pheochromocytoma. Their method of diagnosis should have been based on pathology. We excluded specific subtypes or syndromes related to pheochromocytoma, or specific ages or gender. Also we excluded studies before 1993 (JNC5) which no definition of hypertension was presented. 37 articles were chosen finally. DATA EXTRACTION: Two authors reviewed data from articles independently and gave discrepancies to third author for decision. The aim was extraction of raw numbers of patients having defined signs or symptoms, and draw 2 * 2 tables if data available. We meta-analyzed sensitivities by Statsdirect and Likelihood Ratios by Meta-disc soft wares. Because our data was heterogeneous based on I(2) > 50 % (except negative Likelihood ratio of hypertension), we used random effect model for doing meta-analysis. We checked publication bias by drawing Funnel plot for each sign/symptom, and also Egger test. DATA SYNTHESIS: The most prevalent signs and symptoms reported were hypertension (pooled sensitivity of 80.7 %), headache (pooled sensitivity of 60.4 %), palpitation (pooled sensitivity of 59.3 %) and diaphoresis (pooled sensitivity of 52.4 %). The definition of orthostatic hypotension was different among studies. The sensitivity was 23-50 %. Paroxysmal hypertension, chest pain, flushing, and weakness were the signs/symptoms which had publication bias based on Funnel plot and Egger test (P value < 0.05). Seven of the articles had control group, and could be used for calculating LR of signs/symptoms. Diaphoresis (LR+ 2.2, LR 0.45), Palpitation (LR+ 1.9, LR-0.52) and headache (LR+ 1.6, LR-0.24) were significant symptoms in clinical diagnosis of pheochromocytoma. Other signs and symptoms had been reported in only one study and could not have been meta analyzed. Classic triad of headache, palpitation and diaphoresis in hypertensive patients had the LR+ 6.312 (95 % CI 0.217-183.217) and LR-0.139 (95 % CI 0.059 0.331). Surprisingly, hypertension was not important in clinical suspicion of pheochromocytoma, and even normotension increased the probability of the disease. CONCLUSIONS: By available data, there is no single clinical finding that has significant value in diagnosis or excluding pheochromocytoma. Combination of certain symptoms, signs and para-clinical exams is more valuable for physicians. Further studies should be done, to specify the value of clinical findings.Until that time the process of diagnosis will be based on clinical suspicion and lab tests followed by related imaging. PMID- 26998446 TI - Acceptability and Utilization of Community Health Workers after the Adoption of the Integrated Community Case Management Policy in Kabarole District in Uganda. AB - BACKGROUND: Malaria, pneumonia and diarrhea remains to be the major causes of morbidity and mortality among children in Uganda. To address such challenges, the government adopted a national policy on Integrated Community Case Management (ICCM) for malaria, pneumonia and diarrhea in 2010. The aim of this study was to assess household access, utilization and acceptability of ICCM services in Kabarole District. METHODS: The study was carried out between 22nd November to 4th December, 2014 in Rwimi sub-county, Kabarole district. A cross sectional household survey was conducted amongst caretakers of children below 5 years of age and a total of 384 respondents were interviewed about distance from nearest health facility and community health worker, socio-demographic characteristics, type of housing, history of fever, health-seeking behavior, perceptions of quality and utilization of ICCM services. Data was cleaned, coded and analysed using STATA 14.0 to produce results. RESULTS: Most 53.1% of the studied children were males and their age ranged from 1-52 months. Nearly all the care takers, 97.1% (373/384) had utilized health services for their children in the three proceeding months to the study and of those, 0.5% (2/373) sought from a traditional healer, 8.6% (32/373) sought treatment at home, 27.3% (102/373) from community health worker, 27.3% (102/373) from government health unit and 36.2% (133/373) from non-government health units. The caretakers who stay near CHWs are more likely to utilize ICCM services than those staying near health facilities (P=0.001). The majority 65.6% of the caretakers stay near CHWs and use only 10 minutes to reach the CHWs. Trust in CHWs [AOR 0.85, 95%CI [0.641-1.135]], level of awareness [AOR 0.73, 95%CI [0.538-0.979]] and distance (<=1 km) to CHWs [AOR 1.65, 95%CI [1.075-2.522]] are positively associated with the utilisation of ICCM services. CONCLUSION: The implementation of ICCM policy in kabarole has been an effective approach in increasing the utilization of malaria, diarrhea and pneumonia treatment services and hence increasing access to health services at community level. Trust in the CHWs, level of community awareness and distance to the CHWs are positively associated with the utilisation of ICCM services. PMID- 26998447 TI - DRUG THERAPY IN KNEE OSTEOARTHROSIS. AB - Clinical treatment for osteoarthritis (OA) is very important and is based on patient's self care and guided by the physician. Drug therapy is additional to losing weight, improving muscular strength, proprioception, flexibility and range of motion. Between the available drugs for osteoarthritis' treatment, some are basically analgesics and do not interfere on disease's progression; some are anti inflammatory with good analgesic power but with side effects that compromise their prolonged usage; and the structure modifying drugs that slow down the progression of OA. The medications are presented in topic, oral, intra-muscular, intra-venous and intra-articular forms. The hyaluronic acid has various presentations with good analgesic effect and some evidence of structure modifying property. There is IA evidence level for the use of diacerhein and of glucosamine to slow down the disease. Still, more technology for diagnosis and therapy control of OA is necessary to define the efficacy of other drugs. PMID- 26998448 TI - EVALUATION OF TERMINAL VERTEBRAL PLATE ON CERVICAL SPINE AT DIFFERENT AGE GROUPS AND ITS CORRELATION WITH INTERVERTEBRAL DISC THICKNESS. AB - To evaluate, by means of histomorphometry, terminal vertebral plate thickness, intervertebral disc thickness and its correlation on different age groups, seeking to identify its correlation. METHODS: C4-C5 and C5-C6 cervical segments removed from human cadavers of both genders were assessed and divided into five groups of 10-year age intervals, from 21 years old. TVP and intervertebral disc thickness evaluation was made by means of histomorphometry of histological slides stained with hematoxylin and eosyn. Lower C4 TVP, upper C5 TVP, and upper C6 TVP de were compared between each other and to the interposed intervertebral disc thickness between relevant TVP. RESULTS: The thickness of terminal vertebral plates adjacent to the same ID did not show statistic differences. However, the comparison of upper and lower vertebral plates thickness on the same cervical vertebra (C5), showed statistical difference on all age groups studied. We found a statistical correlation coefficient above 80% between terminal vertebral plate and adjacent intervertebral disc, with a proportional thickness reduction of both structures on the different cervical levels studied, and also on the different age groups assessed. CONCLUSION: Terminal vertebral plate shows a morphologic correlation with the intervertebral disc next to it, and does not show correlation with the terminal vertebral plate on the same vertebra. PMID- 26998449 TI - HIP ARTHROSCOPY IN ATHLETES. AB - To confirm the therapeutic importance of hip arthroplasty in athletes whose pain precludes sportive function of the hip joint, being able to minimize it to the extent of helping on the return of sports practice at satisfactory levels. METHODS: 49 athlete patients (51 hips) submitted to hip arthroscopy complaining of pain and inability to practice sports were assessed. Follow-up time ranged from 12 to 74 months (mean: 39.0 months). Preoperatively, pain site, severity according to Facial Expression Scale (FES) and the degree of disability using the modified Harris Hip Score (HHS) were assessed. Different diagnoses were provided, which led to the indication of arthroscopy, such as femoralacetabular impact, acetabular lip injury not secondary to femoral-acetabular impact, etc. Postoperatively, the patients were assessed by using the same methods as used at baseline and by the subjective analysis of return to sports activities. RESULTS: Based on pre-and postoperative HHS and FES, the statistical analysis showed significance between values. We found some improvement in all cases and return to sports activities at a satisfactory level in most of the cases. CONCLUSION: As a result of our study, we confirm that arthroscopy in athletes with local hip injuries is an effective technique, able to promote the return to sports practice in most of the cases, without pain, and with an effective joint function, provided well indicated. PMID- 26998450 TI - EFFECTS OF CHEMICAL PROCESSING AND OXIDE ETHYLENE STERILIZATION ON CORTICAL AND CANCELLOUS RAT BONE: A LIGHT AND ELECTRON SCANNING MICROSCOPY STUDY. AB - To evaluate, under microscopic examination, the structural changes displayed by the trabecular and cortical bones after being processed chemically and sterilized by ethylene oxide. METHODS: Samples of cancellous and cortical bones obtained from young female albinus rats (Wistar) were assigned to four groups according to the type of treatment: Group I- drying; Group II- drying and ethylene oxide sterilization; III- chemical treatment; IV- chemical treatment and ethylene oxide sterilization. Half of this material was analyzed under ordinary light microscope and the other half using scanning electron microscopy. RESULTS: In all the samples, regardless the group, there was good preservation of the general morphology. For samples submitted to the chemical processing there was better preservation of the cellular content, whereas there was amalgamation of the fibres when ethylene oxide was used. CONCLUSION: Treatment with ethylene oxide caused amalgamation of the fibers, possibly because of heating and the chemical treatment contributed to a better cellular preservation of the osseous structure. PMID- 26998451 TI - POSTERIOR INTERBONE ARTERY FLAP FOR COVERING SERIOUS FOREARM, WRIST AND HAND INJURIES. AB - To assess the results achieved with posterior interbone artery flap covering serious injuries of the distal third of the forearm, wrist and hand, evaluating the degree of effectiveness of this procedure. METHODS: 35 patients with serious injuries of the distal third of upper limbs were studied. We assessed the kind of trauma, injury site, flap size, skin coverage need, clinical outcome and complications. RESULTS: The most frequent mechanism of trauma was motorcycle accident. The most commonly affected regions were: dorsal hand, wrist volar regions and the first commissure. In all patients, the flap size was enough to cover key tissues exposed by the injury. The donor area did not show complications, being primarily closed in 23 cases. The outcomes were good for 31 cases. In 22 patients, no complication was found, and the flap was completely lost in four. CONCLUSION: Posterior interbone artery flap provides good outcomes in covering serious injuries of the distal third of upper limbs, leading to a stable and reliable coverage, not compromising key irrigating arteries of the hand, enabling the performance of reconstruction procedures. Therefore, this is a useful alternative in such cases. PMID- 26998452 TI - A NEW APPROACH TO PARTIALKNEE ENDOPROSTHESIS IN PRIMARY BONE SARCOMAS. AB - Partial knee endoprosthesis to bone sarcomas resections seems to be a good solution to treat this immature skeletal patients. The purpose of this study is to evaluate the functional score in fourteen patients, advantages and the technique indications. METHODS: Retrospective analysis was done to assess in this group of patients the functional evolution and the possible complications of the procedure. 14 patients between 10 and 22 years functionally evaluated in Ennekin/ISOLS (International Society of Limb Salvage) criteria, being all of them operated in the same institution by the same surgeon. Were used distal femur and proximal tibia partial endoprosthesis. RESULTS: General analysis demonstrated that the functional results were over than 67 percent (ISOLS criteria) in 78,6 percent of the patients, being considered excellent. 21,4 percent were considered good results, being between 50 and 66 percent. Bone storage was preserved when avoiding the adjacent segment resection. Surgery time was not prolonged in ligament reconstruction. CONCLUSION: Knee partial endoprosthesis are less damage to bone storage in young patients. The critics about the bad functional results are being supplied by new surgical techniques, excellent rehabilitation protocols, implants technology and the consequent learning curve. This option of treatment permits the preservation of healthy bone and provides the possibility of a revision replacement less aggressive. PMID- 26998453 TI - ARTHROSCOPIC TREATMENT OF ACROMIOCLAVICULAR JOINT DISLOCATION BY TIGHT ROPE TECHNIQUE (ARTHREX((r))). AB - Presenting the arthroscopic treatment by Tight Rope - Arthrex((r)) system for acute acromioclavicular dislocation and to evaluate results obtained with this procedure. METHODS: Between August 2006 and May 2007, 10 shoulders of 10 patients with acute acromioclavicular dislocation were submitted to arthroscopic repair using the Tight Rope - Arthrex((r)) system. Minimum follow-up was 12 months, with a mean of 15 months. Age ranged from 26 to 42, mean 34 years. All patients were male. Radiology evaluation was made by trauma series x-ray. The patients were assisted in the first month weekly and after three months after the procedure. Clinical evaluation was based on the University of California at Los Angeles (UCLA) criteria. RESULTS: All patients were satisfied after the arthroscopic procedure and the mean UCLA score was 32,5. CONCLUSION: The arthroscopic treatment by Tight Rope - Arthrex((r)) system for acute acromioclavicular dislocation showed to be an efficient technique. PMID- 26998454 TI - PROTECTION DEVICE ON THE REPAIR OF RUPTURES OF KNEE EXTENSOR MECHANISM. AB - To evaluate results obtained using the protection device technique for osteosintesis or suture of extensor mechanism lesions. MATERIAL AND METHODS: The authors reviewed 18 charts of patients submitted to protection device technique due to traumatic lesion of extensor mechanism that had occurred between the anterior tibial tuberosity and the apical portion of patella. Age ranged from 22 to 69 years, with a mean of 44 years. Male patients prevailed, with 67% of the cases. The most affected spot was, in 83% of the cases, the apical distal third. A protocol was created to collect data, listing the patients and the clinical history from their medical records. RESULTS: The authors observed consolidation of the patella fracture in all 17 patients, and cicatrization of the patellar ligament in one patient. Pain was described in four patients. There were no complications related to the procedure. CONCLUSION: The protection device showed to be efficient when used in surgical treatment of lesions between the apical patella and the anterior tibial tuberosity, providing active and passive mobility in the early postoperative time. PMID- 26998456 TI - THE SUPERFICIAL BRANCH OF THE RADIAL NERVE: A MORPHOLOGIC STUDY. AB - Study the morphology of the superficial branch of the radial nerve (SBRN) of the forearms and wrists of fresh adult human cadavers. METHODS: Twenty three dissections were performed under 3.5x loupe magnification, histological sections of the nerve were obtained in 20 dissections for fascicle identification. RESULTS: The SBRN emerged, in average, at 8.65cm proximal to the radial styloid apophysis (RSA) between the Brachioradialis (BR) and Extensor Carpi Radialis Longus (ECRL) tendons. In 6/23 cases the SBRN emerged between an accessory BR tendon and the main BR tendon. The first branch of the SBRN arose at an average of 4.58 cm proximal to the RSA. A branch running across the RSA was found in 7/23 cases. At that level, the average number of branches crossing the wrist was 3.4. A fascicle count of the nerve and its first branch showed an average of 6.6 and 4.0 fascicles, respectively. CONCLUSION: Our anatomical findings are similar to those in the revised literature and contribute towards a better knowledge of the SBRN. Great caution is required in surgical procedures such as percutaneous bone fixation of the distal 1/3 of the forearm and wrist and particularly, in those susceptible to SBRN injury, as in seven of the 23 cases the SRBN ran directly accross the RSA. The authors recommend performing small longitudinal incisions down to the subcutaneous tissue, separating the nerve branches by blunt soft tissue dissection, with a delicate haemostat, before introducing the Kirschner wires (minimally invasive procedures). PMID- 26998455 TI - EFFECTS OF ZOLEDRONIC ACID ON OOFORECTOMIZED RATS' TIBIAE: A PROSPECTIVE AND RANDOMIZED STUDY. AB - To investigate clinical, biomechanic and histomorphometric effects of zoledronic acid on osteoporotic rats' tibiae after bilateral ooforectomy. METHODS: 40 female Wistar (Rattus novergicus albinus) rats were prospectively studied. On the 60th day of life, the animals were randomized into two groups according to the surgical procedure: bilateral ooforectomy (O) (n=20) and sham surgery ("sham") (P) (n=20). After 30 days, the animals were divided into four groups, according to the administration of zoledronic acid (ZA) 0.1mg/kg or distilled water (DW): OZA (n=10), ODW (n=10), PZA (n=10) and PDW (n=10). After 12 months, the animals were sacrificed, and had their tibiae assessed. In the clinical study, animals' weight was considered; in the biomechanical study, compressive assays were applied and, in the histomorphometric analysis, the bone trabecular area was determined. RESULTS: "O" groups showed a significantly greater weight gain than "P" groups (p=0.005). Groups OZA and PZA showed an insignificant weight gain when compared to ODW (p=0.47) and PDW (p=0.68). The groups receiving zoledronic acid and distilled water were able to bear maximum load, similar (p=0.2), at the moment of fracture. In the groups receiving zoledronic acid, an insignificant increase of the bone trabecular area was found when compared to the groups receiving distilled water (p=0.21). There was a positive correlation between trabecular area and maximum load (p=0.04; r=0.95). CONCLUSION: Zoledronic acid did not significantly influence animals' weight. The results showed an insignificant increase both of the tibial shaft bone resistance and the bone trabecular area. PMID- 26998457 TI - A new era for the RBO. PMID- 26998459 TI - THE IMPORTANCE OF THE DIAGNOSIS OF SUBCHONDRAL FRACTURE OF THE FEMORAL HEAD, HOW TO DIFFERENTIATE IT FROM AVASCULAR NECROSIS AND HOW TO TREAT IT. AB - Subchondral fracture of the femoral head is an uncommon and underdiagnosed affection. The abrupt or gradual onset of groin pain with functional disability on weight-bearing that improves with a resting period should alert the orthopedic surgeon to the possibility of this diagnosis. The differential diagnosis from osteonecrosis of the femoral head can be provided by assessing the different patterns of bone edema on MRI studies of the hip, thus avoiding unnecessary invasive operations on the hip. PMID- 26998458 TI - THE EFFECT OF PHYSICAL TRAINING ON THE LOCOMOTOR APPARATUS IN ELDERLY PEOPLE. AB - Physiological changes taking place on the locomotive apparatus as a result of aging, such as muscular mass loss, body balance loss, reduced bone mass and osteoarthrosis cause limitations to the daily activities of elderly people, compromising their quality of life and making them weaker and dependent. Aged people who regularly practice physical activities have a higher level of functional independence and a better quality of life than the sedentary ones. This article addresses the key physiological changes with aging and provides a review of current literature about the effects of physical exercises on the locomotive apparatus of elderly individuals, specifying the best ways to prescribe physical exercises to this age group. PMID- 26998461 TI - FUNCTIONAL EVOLUTION OF MENISCAL REPAIR USING ABSORBABLE IMPLANTS. AB - To evaluate the functional evolution of knees after repair of longitudinal meniscal rupture with absorbable arrow implant. METHODS: Between June 1997 and February 2001, 23 patients with a mean age of 26.3 years were evaluated. The mean follow-up time was 72.87 months (45-96). We performed 19 medial and 4 lateral meniscal repairs. The patients were pre and postoperatively evaluated regarding joint function according to the Lysholm scale, and, postoperatively, according to IKDC. RESULTS: For better understanding, the 23 treated cases were divided into three groups. Twenty one had ACL injuries, eleven of whom were submitted to ligament reconstruction (Group I). All these 11 cases were regarded as satisfactory. The remaining 10 cases of the 21 with ACL lesion were not submitted to ligament reconstruction (Group II). Of these, 5 evolved satisfactorily, not requiring ligament reconstruction. The remaining five evolved with complaint of ligament instability, being all submitted to reconstruction. Four of these had an integral meniscus and one presented a failure of the medial meniscus. The remaining two cases who did not present ACL injury (Group III), one patient evolved satisfactorily and one developed a failure of the lateral meniscus. According to the Lysholm scale, preoperative mean score was 57.53 and the postoperative mean score was 86.95, evidencing a statistically significant improvement (Wilcoxon p < 0.01). The non-parametric ANOVA was employed for ordinal data with repeated measurements to assess pre- and postoperative measurements, considering Groups I and II. We assessed knee stabilization and found no statistically significant difference between Groups I and II (p = 0.648). Even if there were differences between the two groups, both had the same behavior. On postoperative assessment with IKDC, 4 patients were grade A, 13 were grade B, and 6 were grade C. Two C results were caused by a meniscal rupture. CONCLUSION: Of the 23 patients, only two presented known failures of the sutured meniscus. According to the Lysholm scale, there was a significant improvement in the treated patients. The ACL repair caused no bias on the results. PMID- 26998460 TI - OSTEOSYNTHESIS OF PROXIMAL HUMERAL END FRACTURES WITH FIXED-ANGLE PLATE AND LOCKING SCREWS: TECHNIQUE AND RESULTS. AB - Describe the results of proximal humeral fractures surgically treated with the Philos locking plate system. METHOD: Between March 2003 and October 2004 we prospectively reviewed 24 of 26 patients with proximal humerus fractures treated with a Philos plate. The mean follow-up time was 12 months and the mean age of patients was 57 years. Six patients had four-part proximal humerus fractures, 11 patients had three-part proximal humerus fractures, and nine patients had two part proximal humerus fractures. Clinical evaluation was performed using the University of California at Los Angeles (UCLA) criteria. RESULTS: The mean UCLA score was 30 points (17-34). All fractures showed union. Three patients showed fracture union at varus position. The mean UCLA score for these patients was 27 points. CONCLUSION: Osteosynthesis with Philos plate provides a stable fixation method with good functional outcome. PMID- 26998462 TI - ANATOMIC STUDY OF THE PROXIMAL THIRD OF THE FEMUR: FEMOROACETABULAR IMPACT AND THE CAM EFFECT. AB - To analyze anatomical variations of the proximal end of femur that could cause a femoroacetabular impact. METHODS: 199 skeletically mature anatomical specimens of femurs were used. The femurs were measured in order to determine the anteversion angle of the femoral neck, neckshaft angle, sphericity of the femoral head at anteroposterior and superoinferior, angle between epiphysis and the anterior femoral neck, angle between epiphysis and the neck at lateral plane, anteroposterior distance at 5mm of the head and neck junction and anteroposterior distance of the neck base. RESULTS: we found that the impact subgroup presented a significantly larger junction diameter of 5mm (p = 0.0001) and cam-head (%) (p= 0.0001), while base-cam (%) (p = 0.0001) showed a significantly smaller diameter than the subgroup without impact. It was identified that cam-head (%) <= 80 e base-cam (%) <= 73 were identified as the optimal impact points. CONCLUSION: our study showed that the effect cam, caused by anatomical variations of the proximal femoral end focused the head-neck junction and base of the neck-junction head neck. These rates can be predictive factors of the impact. PMID- 26998463 TI - SHOULDER ARTHROPLASTY RECORDS. AB - The study's objective is to evaluate the characteristics and problems of patients who underwent shoulder arthroplasties between July 2004 and November 2006. METHODOLOGY: During the period of the study, 145 shoulder arthroplasties were performed. A prospective protocol was used for every patient; demographic, clinical and surgical procedure data were collected. All gathered data were included in the data base. The patients were divided in three major groups: fractures, degenerative diseases and trauma sequels. Information obtained from the data base was correlated in order to determine patients' epidemiologic, injuries, and surgical procedure profiles. RESULTS: Of the 145 shoulder arthroplasties performed, 37% presented trauma sequels, 30% degenerative diseases, and 33% proximal humerus fracture. 12% of the cases required total arthroplasties and 88% partial arthroplasties. Five major complications were observed on early postoperative period. CONCLUSION: Shoulder arthroplasties have become a common procedure in orthopaedic practice. Surgical records are important in evidencing progressive evolution and in enabling future clinical outcomes evaluation. PMID- 26998465 TI - COMPLICATIONS RESULTING FROM THE USE OF METAL ANCHORS IN SHOULDER ARTHROSCOPY. AB - To identify the complications concerning the use of metal anchors in shoulder arthroscopic procedures. METHODS: 28 shoulders of 28 patients (23 male and 5 female) have been re-operated in the period between December 1997 and August 2007, at Hospital Ortopedico, Belo Horizonte Hospital and Military Police Hospital in Belo Horizonte, MG, as a result of complications such as loose anchors and prominent anchors. The primary surgeries intended to treat 20 anterior traumatic instabilities (71.5%), one posterior instability (3.5%), one slap injury (3.5%), six procedures for treating injuries on the rotator cuff (21.5%). We used the X-ray classification suggested by Samilson and Prieto and Outerbridge arthroscopic classification for assessing patients' degree of arthrosis. All patients were evaluated by the UCLA (University of California at Los Angeles) index criteria. RESULTS: In all patients, arthroscopic reviews were made. In two cases, after anchors removal, clinical signs of instability were seen, leading to the decision of providing open stabilization by Latarjet-Patte technique. CONCLUSION: the complications with metallic-suture anchors result from inappropriate surgical techniques applied in arthroscopy. PMID- 26998464 TI - FUNCTIONAL PERFORMANCE AND KNEE LAXITY IN NORMAL INDIVIDUALS AND IN INDIVIDUALS SUBMITTED TO ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION. AB - The aim of this study was to analyze the correlation between deficits in the isokinetic peak torque of the knee extensors and flexors with hop tests, postoperative knee laxity and functional scores in normal and ACL- reconstructed subjects with patellar tendon and hamstring tendon autografts. METHODS: Sixty male subjects were enrolled and subdivided into three groups: Twenty subjects without knee injuries (GC group) and two groups of 20 subjects submitted to ACL reconstruction with patellar tendon (GTP group) and hamstrings autograft (GTF group). RESULTS: The results showed significant correlation between knee extensors peak torque and performance in the hop tests for GTF and GC groups. There are no significantly correlations between post op knee laxity and Lysholm score compared with the hop tests and peak torque deficits. Concerning the differences between groups, the GTP group showed greater peak torque deficits in knee extensors, worst Lysholm scores and higher percentage of individuals with lower limb symmetry index (ISM) < 90% in both hop tests when compared to the other two groups. CONCLUSION: It is not recommendable to use only one measurement instrument for the functional evaluation of ACL-reconstructed patients, because significant correlation between peak torque, subject's functional score, knee laxity and hop tests were not observed in all groups. PMID- 26998466 TI - EXTENSIVE ROTATOR CUFF INJURIES: AN EVALUATION OF ARTHROSCOPIC REPAIR OUTCOMES. AB - To assess the outcomes of the surgical treatment of extensive rotator cuff injuries through arthroscopy. METHODS: Between June 1998 and October 2006, 61 patients with extensive rotator cuff injuries and submitted to surgical arthroscopy technique by the Shoulder and Elbow Group of the Department of Orthopaedics and Traumatology, Santa Casa de Misericordia Medical School were reassessed. The study included all patients with at least two tendons affected or with retraction at least on two tendons up to the glenoidal cavity edge and with at least 12 months of follow-up. RESULTS: According to UCLA's evaluation criteria, 54 (89%) patients showed excellent or good outcomes; no fair outcome in none of the patients; and seven (11%) poor outcomes. A satisfaction rate of 92% was reported. Postoperative joint motion went from a mean lifting value of 93 degrees to 141 degrees , the mean lateral rotation went from 32 degrees to 48 degrees and the mean medial rotation went from L1 to T10. These differences were regarded as statistically significant. CONCLUSION: The arthroscopic repair of extensive rotator cuff injuries leads to satisfactory outcomes for most of the patients, with a high satisfaction degree. PMID- 26998467 TI - MOSAICPLASTY WITH PERIOSTEAL GRAFT FOR RESURFACING LOCAL FULL-THICKNESS CHONDRAL DEFECTS OF THE KNEE. AB - INTRODUCTION AND OBJECTIVES: Clinical and functional assessment comparing cases of full-thickness chondral defects (OC) treated with mosaicplasty or mosaicplasty covered with periosteum (mosaicambium). METHODS: 20 knees with chondral defect, (10 mosaicplasty/10 mosaicambium) were operated between 1999 and 2005. All patients were clinically assessed preoperatively using the ICRS scale, VAS scale, X-ray and MRI. During 2008, we reviewed patients using the same protocol. For statistical purposes, the patients were divided into two groups, according to the surgical technique. Statistical analysis was performed with EPI2000 program, using chi-squared test and Student's t test, with a significance level of 0.05. RESULTS: Preoperatively, all patients were in group C/D (ICRS scale). In 2008, 18 cases were in groups A and B according to the ICRS scale (12 in A). Between groups, there were no statistical differences. The X-ray study revealed no changes in 55% of cases. DISCUSSION: With no differences, why mosaicambium option? Morbidity on graft donor zones is not negligible. Mosaicambium uses less chondral grafts, reducing the potential for morbidity at graft donor zones. CONCLUSION: The mosaicambium technique is an excellent alternative for chondral defects greater than 2 cm2. "... articular cartilage defects are a troublesome thing ... they don't heal ...". William Hunter (1718-1783). PMID- 26998468 TI - Conflict of interest. PMID- 26998469 TI - The Feasibility of At-Home iPad Cognitive Testing For Use in Clinical Trials. AB - BACKGROUND: Technological advances now make it feasible to administer cognitive assessments at-home on mobile and touch-screen devices such as an iPad or tablet computer. Validation of these techniques is necessary to assess their utility in clinical trials. OBJECTIVES: We used a Computerized Cognitive Composite for Preclinical Alzheimer's Disease (C3-PAD) developed for iPad 1) to determine the feasibility of performing the C3-PAD at home by older individuals without the presence of a trained psychometrician; 2) to explore the reliability of in-clinic compared to at-home C3-PAD performance and 3) to examine the comparability of C3 PAD performance to standardized neuropsychological tests. DESIGN SETTING PARTICIPANTS: Forty-nine cognitively normal older individuals (mean age, 71.467.7 years; 20% non-Caucasian) were recruited from research centers at the Massachusetts General Hospital and Brigham and Women's Hospital. Participants made two in-clinic visits one-week apart and took five 30-minute alternate versions of the C3-PAD at-home measuring episodic memory, reaction time and working memory. MEASUREMENTS: A reliability analysis explored equivalence of the six alternate C3-PAD test versions. A feasibility assessment calculated the percentage of individuals who completed all at-home tests correctly, in contrast to incomplete assessments. Correlational analyses examined the association between C3-PAD-clinic compared to C3-PAD-home assessments and between C3-PAD performance and standardized paper and pencil tests. RESULTS: Excellent reliability was observed among the 6 C3-PAD alternate versions (Cronbach alpha coefficient=0.93). A total of 28 of 49 participants completed all at-home sessions correctly and 48 of 49 completed four out of five correctly. There were no significant differences in participant age, sex or education between complete and incomplete at-home assessments. A single in-clinic C3-PAD assessment and the at-home C3-PAD assessments were highly associated with each other (r2=0.508, p<0.0001), suggesting that at-home tests provide reliable data as in-clinic assessments. There was also a moderate association between the at-home C3-PAD assessments and the in-clinic standardized paper and pencil tests covering similar cognitive domains (r2= 0.168, p< 0.003). CONCLUSIONS: Reliable and valid cognitive data can be obtained from the C3-PAD assessments in the home environment. With initial in-clinic training, a high percentage of older individuals completed at-home assessments correctly. At-home cognitive testing shows promise for inclusion into clinical trial designs. PMID- 26998470 TI - The prevalence and distribution of hypodontia in a sample of Qatari patients. AB - OBJECTIVE: The aims of this study were to determine the prevalence of hypodontia in the permanent dentition in a sample of Qatari patients attending a dental center and to compare the results with the reported findings of other populations. MATERIALS AND METHODS: Orthodontic files including orthopantomographs of 1000 patients (655 females and 345 males, 11-36-year-old) were examined and inspected for evidence of hypodontia. RESULTS: The prevalence of hypodontia in the present Qatari sample was 7.8%; 6.9% was in males and 8.2% in females. Hypodontia was found more frequently in the maxilla than in the mandible. The distribution of missing teeth was noticed in the left side more than the right side. The most frequently missing teeth were the maxillary lateral incisors followed by the mandibular second premolars, maxillary second premolars, and mandibular left lateral incisor. The majority of patients with hypodontia had one or two teeth missing, but rarely more than four teeth were missing in the same patient. Bilateral missing teeth in the current study was commonly seen in the maxillary lateral incisor (14.1%) followed by mandibular second premolar (12.8%) and maxillary second premolar (6.4%). CONCLUSIONS: The prevalence of hypodontia in a sample of Qatari individuals was within the range reported in the literature for other populations. The incidence of hypodontia in the anterior segment requires multidisciplinary team approach (orthodontic and prosthodontic) to restore the esthetic and function and improve patient self-esteem. PMID- 26998471 TI - Antimicrobial properties of poly (methyl methacrylate) acrylic resins incorporated with silicon dioxide and titanium dioxide nanoparticles on cariogenic bacteria. AB - AIM: To assess the effects of adding nano-titanium dioxide (nano-TiO2) and nano silicon dioxide (nano-SiO2) and their mixture to poly (methyl methacrylate) (PMMA) to induce antimicrobial activity in acrylic resins. MATERIALS AND METHODS: Acrylic specimens in size of 20 mm * 20 mm * 1 mm of 0.5% and 1% of nano-TiO2 (21 nm) and nano-SiO2 (20 nm) and their mixture (TiO2/SiO2 nanoparticles) (1:1 w/w) were prepared from the mixture of acrylic liquid containing nanoparticles and acrylic powder. To obtain 0.5% and 1% concentration, 0.02 g and 0.04 g of the nanoparticles was added to each milliliter of the acrylic monomer, respectively. Antimicrobial properties of six specimens of these preparations, as prepared, were assessed against planktonic Lactobacillus acidophilus and Streptococcus mutans at 0, 15, 30, 45, 60, 75, and 90 min follow-up by broth dilution assay. The specimens of each group were divided into three subgroups: Dark, daylight, or ultraviolet A (UVA). The percent of bacterial reduction is found out from the counts taken at each time point. STATISTICAL ANALYSIS: Data were analyzed using one-way analysis of variance and Tukey's post hoc analysis. RESULTS: Exposure to PMMA containing the nanoparticles reduced the bacterial count by 3.2-99%, depending on the nanoparticles, bacterial types, and light conditions. Planktonic cultures of S. mutans and L. acidophilus exposed to PMMA containing 1% of TiO2/SiO2 nanoparticles showed a significant decrease (P < 0.001) (98% and 99%, respectively) in a time-dependent manner under UVA. The S. mutans and L. acidophilus counts did not significantly decrease in PMMA containing 0.5% nano TiO2 and PMMA containing 0.5% nano-SiO2 in the dark. No statistically significant reduction (P > 0.05) was observed in the counts of S. mutans and L. acidophilus in PMMA without the nanoparticles exposed to UVA. CONCLUSIONS: PMMA resins incorporated with TiO2/SiO2 nanoparticles showed strong antimicrobial activity against the cariogenic bacteria. PMID- 26998472 TI - Comparison of three different sterilization and disinfection methods on orthodontic markers. AB - BACKGROUND: Marking pencils which are frequently used in orthodontics may cause microbial contamination. The purpose of this study was to evaluate and compare the effectiveness of three disinfection and sterilization methods (autoclave, glutaraldehyde solution, and Deconex spray) on orthodontic markers. MATERIALS AND METHODS: One hundred and twenty orthodontic markers were divided into four groups each 30 pencils: One control group and three groups for three different disinfection/sterilization methods. To evaluate the effectiveness of these methods, pencils were initially contaminated by common pathogen by immersing the pencils in a suspension containing 1.5 * 10(8) CFU/ml organisms. Then, the pencils were subjected to corresponding disinfection/sterilization methods, and the number of remaining microorganisms was calculated and compared with control group. RESULTS: In the control group, the mean number of Escherichia coli was significantly higher than the other two microorganisms (P = 0.01, P = 0.031). However, the mean numbers of Staphylococcus aureus and Candida albicans were not significantly different (P = 0.1). After sterilization with autoclave and glutaraldehyde, no microbial growth was observed, whereas after disinfection with Deconx spray some colonies of microorganisms still could be observed. CONCLUSION: Autoclaving and glutaraldehyde solution are the best methods for disinfecting orthodontic markers. PMID- 26998473 TI - Effects of two erbium-doped yttrium aluminum garnet lasers and conventional treatments as composite surface abrasives on the shear bond strength of metal brackets bonded to composite resins. AB - BACKGROUND: Bonding brackets to dental surfaces restored with composites are increasing. No studies to date have assessed the efficacy of laser irradiation in roughening of composite and the resulted shear bond strength (SBS) of the bonded bracket. We assessed, for the 1(st) time, the efficacy of two laser beams compared with conventional methods. MATERIALS AND METHODS: Sixty-five discs of light-cured composite resin were stored in deionized distilled water for 7 days. They were divided into five groups of 12 plus a group of five for scanning electron microscopy (SEM): Bur-abrasion followed by phosphoric acid etching (bur PA), hydrofluoric acid conditioning (HF), sandblasting, 3 W and 2 W erbium-doped yttrium aluminum garnet laser irradiation for 12 s. After bracket bonding, specimens were water-stored (24 h) and thermocycled (500 cycles), respectively. SBS was tested at 0.5 mm/min crosshead speed. The adhesive remnant index (ARI) was scored under *10 magnification. SEM was carried out as well. Data were analyzed using analysis of variance (ANOVA), Kruskal-Wallis, Tukey, Dunn, one sample t-test/Wilcoxon tests, and Weibull analysis (alpha =0.05). RESULTS: The SBS values (megapascal) were bur-PA (11.07 +/- 1.95), HF (19.70 +/- 1.91), sandblasting (7.75 +/- 1.10), laser 2 W (15.38 +/- 1.38), and laser 3 W (20.74 +/ 1.73) (compared to SBS = 6, all P = 0.000). These differed significantly (ANOVA P = 0.000) except HF versus 3 W laser (Tukey P > 0.05). ARI scores differed significantly (Kruskal-Wallis P = 0.000), with sandblasting and 2 W lasers having scores inclined to the higher end (safest debonding). Weibull analysis implied successful clinical outcome for all groups, except for sandblasting with borderline results. CONCLUSION: Considering its high efficacy and the lack of adverse effects bound with other methods, the 3 W laser irradiation is recommended for clinical usage. PMID- 26998474 TI - Comparison of shear bond strength to clinically simulated debonding of orthodontic brackets: An in vitro study. AB - OBJECTIVES: To assess in vitro the quantitative and qualitative debonding behavior of the AEZ debonding plier, compared to shear debonding force, in debonding orthodontic metal brackets. MATERIALS AND METHODS: Thirty-two extracted premolars bonded with metal brackets were randomly divided into two equal groups according to the type of simulated debonding method; compressive bond strength (CBS) group using AEZ debonding plier (Ormco Corporation, USA) attached to the Instron machine, and shear bond strength (SBS) group using regular Instron attachments. All teeth were subjected to debonding forces, and debonding strength was assessed. The buccal surfaces were then examined, under a stereomicroscope, and adhesive remnants were scored using adhesive remnant index (ARI). Debonding strengths comparison was performed using the independent sample t-test. ARI score comparison was performed using the Mann-Whitney U-test. Correlation between debonding strength and ARI scores was performed using the Spearman correlation. RESULTS: There was no significant difference in mean debonding strength between the SBS (M = 6.17 +/- 0.77 MPa) and CBS (M = 6.68 +/- 1.67 MPa) groups (P > 0.05). The CBS group showed significantly less adhesive remnants than the SBS group (P < 0.05); 62.5% of CBS group had ARI score 1, whereas 68.8% of SBS group had ARI score 3. No significant correlation between ARI and debonding strength was found (P < 0.05). CONCLUSION: SBS was found to produce similar debonding strength to the AEZ debonding plier in vitro. However, the AEZ debonding plier resulted in less adhesive remnant which is of great advantage for reducing chair time during cleanup after debonding brackets. PMID- 26998475 TI - Simplified treatment mechanics with a miniscrew for a case of canine impaction. AB - With the introduction of miniscrews into the orthodontic field, the efficiency and effectiveness of treating complex cases have significantly improved. Biomechanical considerations, especially relating to anchorage control have become less of a concern and side effects, as a consequence, have become minimal. This article reports on a canine impaction case in which an orthodontic miniscrew has been used to effectively and efficiently pull the canine, thereby reducing anchorage unit side effects and simplifying treatment mechanics. PMID- 26998476 TI - Surgery-first orthognathic approach case series: Salient features and guidelines. AB - Conventional orthognathic surgery treatment involves a prolonged period of orthodontic treatment (pre- and post-surgery), making the total treatment period of 3-4 years too exhaustive. Surgery-first orthognathic approach (SFOA) sees orthognathic surgery being carried out first, followed by orthodontic treatment to align the teeth and occlusion. Following orthognathic surgery, a period of rapid metabolic activity within tissues ensues is known as the regional acceleratory phenomenon (RAP). By performing surgery first, RAP can be harnessed to facilitate efficient orthodontic treatment. This phenomenon is believed to be a key factor in the notable reduction in treatment duration using SFOA. This article presents two cases treated with SFOA with emphasis on "case selection, treatment strategy, merits, and limitations" of SFOA. Further, salient features comparison of "conventional orthognathic surgery" and "SFOA" with an overview of author's SFOA treatment protocol is enumerated. PMID- 26998477 TI - Successful Image-Guided Retrieval of an Embolized Fragment of a Fractured Haemodialysis Catheter Tip from the Pulmonary Artery. AB - BACKGROUND: Cuffed, double-lumen, tunneled haemodialysis catheters are a common means of vascular access in paediatric haemodialysis, particularly in infants. Haemodialysis catheter fracture with distal embolization is a rare complication. CASE REPORT: A 2-year-old boy was receiving chronic haemodialysis via a right internal jugular cuffed, double-lumen, tunneled haemodialysis catheter, inserted 3 months previously. He was asymptomatic and was incidentally found to have had embolization of a fractured catheter tip into a segmental branch of the left pulmonary artery. The catheter was replaced and the embolized fragment successfully retrieved, non-surgically, using an image-guided endovascular approach with a loop snare device. CONCLUSION: Haemodialysis catheter fracture with distal embolization is a rare complication in both adults and children and is usually associated with prolonged use and catheter fatigue. Retrieval of the embolized fragment should always be attempted to prevent possible complications. Awareness of this potential complication is important to facilitate diagnosis and management. PMID- 26998478 TI - Design and Performance of a Multi-Point Scan Confocal Microendoscope. AB - Confocal fluorescence microendoscopy provides high-resolution cellular-level imaging via a minimally invasive procedure, but requires fast scanning to achieve real-time imaging in vivo. Ideal confocal imaging performance is obtained with a point scanning system, but the scan rates required for in vivo biomedical imaging can be difficult to achieve. By scanning a line of illumination in one direction in conjunction with a stationary confocal slit aperture, very high image acquisition speeds can be achieved, but at the cost of a reduction in image quality. Here, the design, implementation, and experimental verification of a custom multi-point aperture modification to a line-scanning multi-spectral confocal microendoscope is presented. This new design improves the axial resolution of a line-scan system while maintaining high imaging rates. In addition, compared to the line-scanning configuration, previously reported simulations predicted that the multi-point aperture geometry greatly reduces the effects of tissue scatter on image quality. Experimental results confirming this prediction are presented. PMID- 26998479 TI - Whole Exome- and mRNA-Sequencing of an AT/RT Case Reveals Few Somatic Mutations and Several Deregulated Signalling Pathways in the Context of SMARCB1 Deficiency. AB - BACKGROUND: AT/RTs are rare aggressive brain tumours, mainly affecting young children. Most cases present with genetic inactivation of SMARCB1, a core member of the SWI/SNF chromatin-remodeling complex. We have performed whole exome- and mRNA-sequencing on an early onset AT/RT case for detection of genetic events potentially contributing to the disease. RESULTS: A de novo germline variant in SMARCB1, c.601C>T p.Arg201*, in combination with somatic deletion of the healthy allele is likely the major tumour causing event. Only seven somatic small scale mutations were discovered (hitting SEPT03, H2BFM, ZIC4, HIST2H2AB, ZIK1, KRTAP6 3, and IFNA8). All were found with subclonal allele frequencies (range 5.7-17%) and none were expressed. However, besides SMARCB1, candidate genes affected by predicted damaging germline variants that were expressed were detected (KDM5C, NUMA1, and PCM1). Analysis of differently expressed genes revealed many dysregulated pathways in the tumour, such as cell cycle, CXCR4 pathway, GPCR signalling, and neuronal system. FGFR1, CXCR4, and MDK were upregulated and may represent possible drug targets. CONCLUSION: The loss of SMARCB1 function leads to AT/RT development and deregulated genes and pathways. Additional predisposing events may however contribute. Studies utilizing NGS technologies in larger cohorts will probably identify recurrent genetic and epigenetic alterations and molecular subgroups with implications for clinical practice and development of targeted therapies. PMID- 26998480 TI - Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Surgery in the Sugammadex Era: A Retrospective Study. AB - BACKGROUND: Residual neuromuscular block (NMB) after general anesthesia has been associated with pulmonary dysfunction and hypoxia, which are both associated with postoperative delirium (POD). We evaluated the effects of sugammadex on POD in elderly patients who underwent hip fracture surgery. METHODS: Medical records of 174 consecutive patients who underwent hip fracture surgery with general anesthesia were reviewed retrospectively to compare the perioperative incidence of POD, pulmonary complications, time to extubation, incidence of hypoxia, and laboratory findings between patients treated with sugammadex and those treated with a conventional cholinesterase inhibitor. RESULTS: The incidence of POD was not significantly different between the two groups (33.3% versus 36.5%, resp.; P = 0.750). Postoperative pulmonary complications and laboratory findings did not showed significant intergroup difference. However, time to extubation (6 +/- 3 versus 8 +/- 3 min; P < 0.001) and the frequency of postoperative hypoxia were significantly lower (23% versus 43%; P = 0.010) in the sugammadex group than in the conventional cholinesterase inhibitor group. CONCLUSION: Sugammadex did not reduce POD or pulmonary complications compared to conventional cholinesterase inhibitors, despite reducing time to extubation and postoperative hypoxia in elderly patients who underwent hip fracture surgery under general anesthesia. PMID- 26998481 TI - Optimization of Cultural Conditions for Antioxidant Exopolysaccharides from Xerocomus badius Grown in Shrimp Byproduct. AB - To optimize the production conditions for exopolysaccharides with higher antioxidant activities from Xerocomus badius cultured in shrimp byproduct medium, Plackett-Burman design, path of steepest ascent, and response surface methodology were explored. Based on the results of Plackett-Burman design and path of steepest ascent, a Box-Behnken design was applied to optimization and the regression models. The optimal cultural condition for high yield and antioxidant activity of the exopolysaccharides was determined to be 10.347% of solid-to liquid ratio, a 4.322% content of bran powder, and a 1.217% concentration of glacial acetic acid. Culturing with the optimal cultural conditions resulted in an exopolysaccharides yield of 4.588 +/- 0.346 g/L and a total antioxidant activity of 2.956 +/- 0.105 U/mg. These values are consistent with the values predicted by the corresponding regression models (RSD < 5%). PMID- 26998482 TI - Altered Resting-State Amygdala Functional Connectivity after Real-Time fMRI Emotion Self-Regulation Training. AB - Real-time fMRI neurofeedback (rtfMRI-nf) is a promising tool for enhancing emotion regulation capability of subjects and for the potential alleviation of neuropsychiatric disorders. The amygdala is composed of structurally and functionally distinct nuclei, such as the basolateral amygdala (BLA) and centromedial amygdala (CMA), both of which are involved in emotion processing, generation, and regulation. However, the effect of rtfMRI-nf on the resting-state functional connectivity (rsFC) of BLA and CMA remains to be elucidated. In our study, participants were provided with ongoing information on their emotion states by using real-time multivariate voxel pattern analysis. Results showed that participants presented significantly increased rsFC of BLA and CMA with prefrontal cortex, rostral anterior cingulate cortex, and some others related to emotion after rtfMRI-nf training. The findings provide important evidence for the emotion regulation effectiveness of rtfMRI-nf training and indicate its usefulness as a tool for the self-regulation of emotion. PMID- 26998483 TI - Carnitine and/or Acetylcarnitine Deficiency as a Cause of Higher Levels of Ammonia. AB - Blood carnitine and/or acetylcarnitine deficiencies are postulated in the literature as possible causes of higher ammonia levels. The aim of this study was to investigate if the use of valproic acid, the age of the patients, or certain central nervous system pathologies can cause carnitine and/or acetylcarnitine deficiency leading to increased ammonia levels. Three groups of patients were studied: (A) epileptic under phenytoin monotherapy (n = 31); (B) with bipolar disorder under valproic acid treatment (n = 28); (C) elderly (n = 41). Plasma valproic acid and blood carnitine and acyl carnitine profiles were determined using a validated HPLC and LC-MS/MS method, respectively. Blood ammonia concentration was determined using an enzymatic automated assay. Higher ammonia levels were encountered in patients under valproic acid treatment and in the elderly. This may be due to the lower carnitine and/or acetylcarnitine found in these patients. Patients with controlled seizures had normal carnitine and acetylcarnitine levels. Further studies are necessary in order to conclude if the uncontrolled bipolar disorder could be the cause of higher carnitine and/or acetylcarnitine levels. PMID- 26998484 TI - Pacemaker Created in Human Ventricle by Depressing Inward-Rectifier K+ Current: A Simulation Study. AB - Cardiac conduction disorders are common diseases which cause slow heart rate and syncope. The best way to treat these diseases by now is to implant electronic pacemakers, which, yet, have many disadvantages, such as the limited battery life and infection. Biopacemaker has been expected to replace the electronic devices. Automatic ventricular myocytes (VMs) could show pacemaker activity, which was induced by depressing inward-rectifier K(+) current (I K1). In this study, a 2D model of human biopacemaker was created from the ventricular endocardial myocytes. We examined the stability of the created biopacemaker and investigated its driving capability by finding the suitable size and spatial distribution of the pacemaker for robust pacing and driving the surrounding quiescent cardiomyocytes. Our results suggest that the rhythm of the pacemaker is similar to that of the single cell at final stable state. The driving force of the biopacemaker is closely related to the pattern of spatial distribution of the pacemaker. PMID- 26998485 TI - The Efficacy and Safety of Fractional CO2 Laser Combined with Topical Type A Botulinum Toxin for Facial Rejuvenation: A Randomized Controlled Split-Face Study. AB - OBJECTIVE: We evaluated synergistic efficacy and safety of combined topical application of Botulinum Toxin Type A (BTX-A) with fractional CO2 laser for facial rejuvenation. METHODS: Twenty female subjects were included for this split face comparative study. One side of each subject's cheek was treated with fractional CO2 plus saline solution, and the other side was treated with fractional CO2 laser plus topical application of BTX-A. Patients received one session of treatment and evaluations were done at baseline, one, four, and twelve weeks after treatment. The outcome assessments included subjective satisfaction scale; blinded clinical assessment; and the biophysical parameters of roughness, elasticity, skin hydration, transepidermal water loss (TEWL), and the erythema and melanin index. RESULTS: BTX-A combined with fractional CO2 laser sides showed higher physician's global assessment score, subject satisfaction score, roughness, skin hydration, and skin elasticity compared to that of fractional CO2 plus saline solution side at 12 weeks after treatment. TEWL and erythema and melanin index showed no significant differences between two sides at baseline, one, four, and twelve weeks after treatment. CONCLUSION: Topical application of BTX-A could enhance the rejuvenation effect of fractional CO2 laser. PMID- 26998486 TI - Adsorption Analysis of Lactoferrin to Titanium, Stainless Steel, Zirconia, and Polymethyl Methacrylate Using the Quartz Crystal Microbalance Method. AB - It is postulated that biofilm formation in the oral cavity causes some oral diseases. Lactoferrin is an antibacterial protein in saliva and an important defense factor against biofilm development. We analyzed the adsorbed amount of lactoferrin and the dissociation constant (K(d)) of lactoferrin to the surface of different dental materials using an equilibrium analysis technique in a 27 MHz quartz crystal microbalance (QCM) measurement. Four different materials, titanium (Ti), stainless steel (SUS), zirconia (ZrO2) and polymethyl methacrylate (PMMA), were evaluated. These materials were coated onto QCM sensors and the surfaces characterized by atomic force microscopic observation, measurements of surface roughness, contact angles of water, and zeta potential. QCM measurements revealed that Ti and SUS showed a greater amount of lactoferrin adsorption than ZrO2 and PMMA. Surface roughness and zeta potential influenced the lactoferrin adsorption. On the contrary, the K(d) value analysis indicated that the adsorbed lactoferrin bound less tightly to the Ti and SUS surfaces than to the ZrO2 and PMMA surfaces. The hydrophobic interaction between lactoferrin and ZrO2 and PMMA is presumed to participate in better binding of lactoferrin to ZrO2 and PMMA surfaces. It was revealed that lactoferrin adsorption behavior was influenced by the characteristics of the material surface. PMID- 26998487 TI - Chemical Ecology of Parasitic Hymenoptera. PMID- 26998488 TI - Establishment and Characterization of a Telomerase-Immortalized Sheep Trophoblast Cell Line. AB - The primary sheep trophoblast cells (STCs) have a finite lifespan in culture. This feature limits the scope for long-term in vitro studies with STCs. This study was an attempt to establish and characterize a telomerase-immortalized sheep trophoblast cell line. STCs were isolated and purified by using Percoll and specific immunoaffinity purification, respectively. The purified STCs were transfected with a plasmid carrying sequences of human telomerase reverse transcriptase (hTERT) to create immortalized sheep trophoblast cell line (hTERT STCs). hTERT-STCs showed a stable expression of hTERT gene, serially passaged for a year, and showed active proliferation without signs of senescence. Cytokeratin 7 (CK-7), secreted human chorionic gonadotrophin subunit beta (CG-beta), placental lactogen (PL), and endogenous jaagsiekte sheep retrovirus (enJSRV) envelope genes were expressed in hTERT-STCs. Transwell cell invasion assay indicated that hTERT-STCs still possessed the same invasive characteristics as normal primary sheep trophoblast cells. hTERT-STCs could not grow in soft agar and did not develop into tumors in nude mice. In this study, we established a strain of immortalized sheep trophoblast cell line which could be gainfully employed in the future as an experimental model to study trophoblast cells with secretory function, invasive features, and probable biological function of enJSRV envelope genes. PMID- 26998489 TI - Genetic Characterization of a Novel Mutant of Peste Des Petits Ruminants Virus Isolated from Capra ibex in China during 2015. AB - Peste des petits ruminants virus (PPRV) is the causative agent of peste des petits ruminants (PPR). The spread of PPR often causes severe economic losses. Therefore, special attention should be paid to the surveillance of PPR emergence, spread, and geographic distribution. Here we describe a novel mutant of PPRV China/XJBZ/2015 that was isolated from Capra ibex in Xinjiang province in China 2015. The sequence analysis and phylogenetic assessment indicate that China/XJBZ/2015 belongs to lineage IV, being closely related to China/XJYL/2013 strain. Interestingly, the V protein sequence of China/XJBZ/2015 showed lower homology with other Chinese PPRVs isolated during 2013 to 2014 (94%~95%), whereas it shared 100% identity with three Tibet strains isolated in China 2007. The 3' UTR, V gene, and C gene were determined to be highly variable. Besides, 29 PPR genomic sequences available in GenBank were analyzed in this study. It is the first time to use PPRV genomic sequences to classify the different lineages which confirmed the lineage clustering of PPRVs using N gene 255 bp fragments and F gene 322 bp fragments. In conclusion, our findings indicate that the PPRVs continue to evolve in China, and some new mutations have emerged. PMID- 26998490 TI - Microelectrical Impedance Spectroscopy for the Differentiation between Normal and Cancerous Human Urothelial Cell Lines: Real-Time Electrical Impedance Measurement at an Optimal Frequency. AB - PURPOSE: To distinguish between normal (SV-HUC-1) and cancerous (TCCSUP) human urothelial cell lines using microelectrical impedance spectroscopy (MUEIS). MATERIALS AND METHODS: Two types of MUEIS devices were designed and used in combination to measure the impedance of SV-HUC-1 and TCCSUP cells flowing through the channels of the devices. The first device (MUEIS-OF) was designed to determine the optimal frequency at which the impedance of two cell lines is most distinguishable. The MUEIS-OF trapped the flowing cells and measured their impedance at a frequency ranging from 5 kHz to 1 MHz. The second device (MUEIS RT) was designed for real-time impedance measurement of the cells at the optimal frequency. The impedance was measured instantaneously as the cells passed the sensing electrodes of MUEIS-RT. RESULTS: The optimal frequency, which maximized the average difference of the amplitude and phase angle between the two cell lines (p < 0.001), was determined to be 119 kHz. The real-time impedance of the cell lines was measured at 119 kHz; the two cell lines differed significantly in terms of amplitude and phase angle (p < 0.001). CONCLUSION: The MUEIS-RT can discriminate SV-HUC-1 and TCCSUP cells by measuring the impedance at the optimal frequency determined by the MUEIS-OF. PMID- 26998491 TI - Exenatide Treatment Causes Suppression of Serum Ghrelin Levels following Mixed Meal Test in Obese Diabetic Women. AB - AIM: To investigate the effect of exenatide treatment on serum ghrelin levels in obese female patients with type 2 diabetes mellitus. METHODS: Fourteen female patients with type 2 diabetes mellitus being treated with metformin and exenatide were enrolled. A mixed meal test was applied to the patients while continuing with their daily medications. Blood samples were taken before and at 60, 120, and 180 minutes following mixed meal test to measure serum total ghrelin, glucose, and insulin levels. The following week, exenatide treatment of the patients was paused for 24 hours and the same experimental procedures were repeated. RESULTS: Serum ghrelin levels were suppressed significantly at 180 minutes with exenatide treatment compared with baseline (294.4 +/- 57.5 versus 234.5 +/- 59.4 pg/mL) (p < 0.001). Serum ghrelin levels at 180 minutes were statistically different when percentage change in serum ghrelin levels after mixed meal tests with and without exenatide usage were compared (p = 0.001). Estimated total area under the curve values for serum ghrelin concentrations was also significantly lower with exenatide compared with omitted treatment (p = 0.035). CONCLUSION: These results suggest that the effect of exenatide on weight loss may be related with the suppression of serum ghrelin levels, which is an orexigenic peptide. PMID- 26998492 TI - Reversibility of beta-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse. AB - Type 2 diabetes (T2D) is characterized by beta-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of beta-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db) to analyze the changes in the expression levels of beta-cell-specific transcription factors (TFs) and functional factors with long-term caloric restriction (CR). Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and beta-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of beta-cell dedifferentiation can intervene by long-term control of calorie intake. Key beta-cell-specific TFs and functional factors play important roles in maintaining beta-cell differentiation. Targeting these factors could optimize T2D therapies. PMID- 26998493 TI - Risk Factors for Foot Amputation in Patients Hospitalized for Diabetic Foot Infection. AB - The aim of this study was to identify and quantify risk factors for amputation in diabetic patients hospitalized for foot infections. This cross-sectional study comprised 100 patients with diabetic infectious complications in the lower limbs. The variables investigated were related to diabetes, infection, and treatment compliance. Multiple Cox regression analysis was performed to identify the variables independently associated with the outcome of amputation. The most prevalent chronic complications were neuropathy and hypertension. Most patients presented with a neuroischemic foot (86%). The Morisky test showed that 72% were not compliant with diabetes treatment. Regarding patient outcome, 61% progressed to amputation, 14% to debridement, and 9% to revascularization. The results showed a 42% higher risk for progression to amputation in patients with previous use of antimicrobials. Also, the amputation risk was 26% higher for those less compliant with diabetes treatment. An increase of one point in the Wagner ulcer classification criteria corresponded to a 65% increase in the risk of amputation. Undergoing conservative, nonsurgical procedures prior to admission provided a 63% reduction in the risk of amputation. Knowledge of these factors is critical to enable multidisciplinary teams to develop treatment plans for these patients so as to prevent the need for amputation. PMID- 26998494 TI - Brain Activation and Psychomotor Speed in Middle-Aged Patients with Type 1 Diabetes: Relationships with Hyperglycemia and Brain Small Vessel Disease. AB - Slower psychomotor speed is very common in patients with type 1 diabetes mellitus (T1D), but the underlying mechanisms are not clear. We propose that hyperglycemia is associated with slower psychomotor speed via disruption of brain activation. Eighty-five adults (48% women, mean age: 49.0 years, mean duration: 40.8) with childhood onset T1D were recruited for this cross-sectional study. Median response time in seconds (longer = worse performance) and brain activation were measured while performing a psychomotor speed task. Exposure to hyperglycemia, measured as glycosylated hemoglobin A1c, was associated with longer response time and with higher activation in the inferior frontal gyrus and primary sensorimotor and dorsal cingulate cortex. Higher activation in inferior frontal gyrus, primary sensorimotor cortex, thalamus, and cuneus was related to longer response times; in contrast, higher activation in the superior parietal lobe was associated with shorter response times. Associations were independent of small vessel disease in the brain or other organs. In this group of middle-aged adults with T1D, the pathway linking chronic hyperglycemia with slower processing speed appears to include increased brain activation, but not small vessel disease. Activation in the superior parietal lobe may compensate for dysregulation in brain activation in the presence of hyperglycemia. PMID- 26998497 TI - The case control studies of HIV and Intestinal parasitic infections rate in active pulmonary tuberculosis patients in Woldia General Hospital and Health Center in North Wollo, Amhara Region, Ethiopia. AB - Tuberculosis remains a major health problem worldwide in the era of HIV/AIDS. Co infection with intestinal parasites has been suggested to worsen the outcome of infection in addition to HIV infection. Hence, adequate information on TB patients with HIV and intestinal parasites infection is being needed to tackle the problem, undertake the integrated prevention and control program. This study was aimed to assess the prevalence of HIV and intestinal parasitic infections in active pulmonary tuberculosis patients compared with their healthy extended family of the subject as a control. A case-control study was carried out from November, 2010 to June, 2011 in Woldia General Hospital and Woldia Health Center. Stool sample were examined using direct technique and formol-ether concentration techniques. Modified acid fast stain was used to identify Oocysts of Cryptosporidium species and Isospora belli. HIV rapid tests were used to screen sero prevalence and AFB smear microscopy for screening Pulmonary TB patients. A total of 100 smear positive TB patients and 168 familial contacts were participated and the overall prevalence of intestinal parasite among TB patients was 49%; compared to 23.2% of the control. 41% of TB patients and 23.8% controls were found to be HIV infected. Double infection with both intestinal parasite and HIV was found in 61% TB patients and 52.5% of the controls. The proportions of TB patients infected with 1, 2, or more species of worms were 73.5%, 26.5% respectively; 82%, 18% were in controls and the odds of being an active TB patient is increased with the number of species of intestinal parasites the person harbors. The current study showed that a significant association between TB/HIV infection and intestinal parasite particularly Strongyloides stercoralis Cryptosporidium parvum and Isospora belli. PMID- 26998499 TI - Efficacy of Environmental Health E-Training for Journalists. AB - Communities report a low level of trust in environmental health media coverage. In order to support risk communication objectives, the goals of the research study were to identify whether or not there is a gap in environmental reporting training for journalists, to outline journalists' methods for gathering environmental health news, to observe journalists' attitudes toward environmental health training and communication, and to determine if electronic training (online/e-training) can effectively train journalists in environmental health topics. The results indicated that environmental journalists have very little to no formal environmental journalism training. In addition, a significant percentage of journalists do not have any formal journalism education. Respondents most preferred to receive continuing environmental journalism training online. Online instruction was also perceived as effective in increasing knowledge and providing necessary reporting tools, even among participants adverse to online instructional methods. Our findings highlight the changing media climate's need for an increase in electronic journalism education opportunities to support environmental health journalism competencies among working professional journalists. PMID- 26998495 TI - Chimeric Antigen Receptor-Modified T Cells for Solid Tumors: Challenges and Prospects. AB - Recent studies have highlighted the successes of chimeric antigen receptor modified T- (CART-) cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. Although antitumor effects were confirmed in vitro and in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. These interventions will make treatment with CART cells an effective and routine therapy for solid tumors. PMID- 26998500 TI - Assessment of Joint Interactions between Respiration and Baroreflex Activity using Joint Symbolic Dynamics in Heart Failure Patients. AB - In this paper we employed a novel approach based on joint symbolic dynamics (JSD) to study interaction between respiratory phase and baroreflex activity. Electrocardiogram (ECG) and blood pressure recordings from six participants with history of heart failure were included in this study. First, the ECG R-peaks and systolic blood pressure indices were detected using parabolic fitting. Second, the respiratory signal was derived from Frank orthogonal ECG leads using QRS slopes and R-wave angles. Third, time series of R-R intervals and systolic blood pressure (SBP) were extracted, and respiratory phases were obtained using the Hilbert transform. Subsequently, each series was transformed into binary symbol vectors based on their successive changes and words of length '2' were formed. Baroreflex patterns were studied using word combinations representing baroreflex activity for specific changes in respiratory phases. Baroreflex activity was significantly higher for alternating low-high/high-low heart rate and SBP during inspiration as compared to continuous increase or decrease in heart rate and SBP ([Formula: see text], wRP=11: 39.1+/-9.3% vs. [Formula: see text], wRP=11: 6.4+/ 3.9%, p<0.0001). PMID- 26998498 TI - Searching the Human Genome for Snail and Slug With DNA@Home. AB - DNA@Home is a volunteer computing project that aims to use Gibbs Sampling for the identification and location of DNA control signals on full genome-scale datasets. A fault tolerant and asynchronous implementation of Gibbs sampling using the Berkeley Open Infrastructure for Network Computing (BOINC) was used to identify the location of binding sites of the SNAI1 (Snail) and SNAI2 (Slug) transcription factors across the human genome. Genes regulated by Slug but not Snail, and genes regulated by Snail but not Slug provided two datasets with known motifs. These datasets contained up to 994 DNA sequences which to our knowledge is largest scale use of Gibbs sampling for discovery of binding sites. 1000 parallel sampling walks were used to search for the presence of 1, 2 or 3 possible motifs using small, medium, and full size sets of these sequences. These runs were performed over a period of two months using over 1500 volunteered computing hosts and generated over 2.2 Terabytes of sampling data. High performance computing resources were used for post processing. This paper presents intra and inter walk analyses used to determine walk convergence. The results were validated against current biological knowledge of the Snail and Slug promoter regions and present avenues for further biological study. PMID- 26998496 TI - The Toll of Vascular Insufficiency: Implications for the Management of Peripheral Arterial Disease. AB - Peripheral artery disease (PAD) can result in limb loss within six months of diagnosis in a subset of patients who cannot undergo endovascular or surgical revascularization yet continues to maintain a marginal position in cardiovascular research. While a body of literature continues to grow describing the role of danger signaling and innate immunity in cardiac biology, the role of these pathways in the ischemic myopathy associated with PAD has not been extensively studied. The following report will review the current literature on the role of Toll-like receptor (TLR) signaling in cardiovascular biology as well as in nonischemic myopathy. While attenuation of TLR signaling has not been shown to be clinically useful in the treatment of infectious inflammation, it may show promise in the management of severe arterial insufficiency. PMID- 26998501 TI - Anterior Cruciate Ligament Injuries in National Football League Athletes From 2010 to 2013: A Descriptive Epidemiology Study. AB - BACKGROUND: There is a high incidence of anterior cruciate ligament (ACL) injuries among National Football League (NFL) athletes; however, the incidence of reinjury in this population is unknown. PURPOSE: This retrospective epidemiological study analyzed all publicly disclosed ACL tears occurring in NFL players between 2010 and 2013 to characterize injury trends and determine the incidence of reinjury. STUDY DESIGN: Descriptive epidemiological study. METHODS: A comprehensive online search identified any NFL player who had suffered an ACL injury from 2010 to 2013. Position, playing surface, activity, and date were recorded. Each player was researched for any history of previous ACL injury. The NFL games database from USA Today was used to determine the incidence of ACL injuries on artificial turf and grass fields. Databases from Pro Football Focus and Pro Football Reference were used to determine the injury rate for each position. RESULTS: NFL players suffered 219 ACL injuries between 2010 and 2013. Forty players (18.3%) had a history of previous ACL injury, with 27 (12.3%) retears and 16 (7.3%) tears contralateral to a previous ACL injury. Five players (2.28%) suffered their third ACL tear. Receivers (wide receivers and tight ends) and backs (linebackers, fullbacks, and halfbacks) had significantly greater injury risk than the rest of the NFL players, while perimeter linemen (defensive ends and offensive tackles) had significantly lower injury risk than the rest of the players. Interior linemen (offensive guards, centers, and defensive tackles) had significantly greater injury risk compared with perimeter linemen. ACL injury rates per team games played were 0.050 for grass and 0.053 for turf fields (P > .05). CONCLUSION: In this retrospective epidemiological study of ACL tears in NFL players, retears and ACL tears contralateral to a previously torn ACL constituted a substantial portion (18.3%) of total ACL injuries. The significant majority of ACL injuries in players with a history of previous ACL injury were retears. Skilled offensive players and linebackers had the greatest injury risk, and significantly more ACL tears occurred among interior linemen than perimeter linemen. The month of August had the highest incidence of ACL injuries, probably because of expanded roster sizes at that point in the NFL season. PMID- 26998502 TI - The Epidemiology of Hip/Groin Injuries in National Collegiate Athletic Association Men's and Women's Ice Hockey: 2009-2010 Through 2014-2015 Academic Years. AB - BACKGROUND: There is limited research regarding the epidemiology of hip/groin injuries in ice hockey, the majority of which is restricted to time-loss injuries only. PURPOSE: To describe the epidemiology of hip/groin injuries in collegiate men's and women's ice hockey from 2009-2010 through 2014-2015. STUDY DESIGN: Descriptive epidemiology study. METHODS: Hip/groin injury data from the National Collegiate Athletic Association Injury Surveillance Program (NCAA-ISP) during the 2009-2010 through 2014-2015 seasons were analyzed. Injury rates, rate ratios (RRs), and injury proportion ratios (IPRs) were reported with 95% confidence intervals (CIs). RESULTS: During the 2009-2010 through 2014-2015 seasons, 421 and 114 hip/groin injuries were reported in men's and women's ice hockey, respectively, leading to injury rates of 1.03 and 0.78 per 1000 athlete-exposures (AEs), respectively. The hip/groin injury rate was greater in men than in women (RR, 1.32; 95% CI, 1.08-1.63). In addition, 55.6% and 71.1% of hip/groin injuries in men's and women's ice hockey, respectively, were non-time loss (NTL) injuries (ie, resulted in participation restriction time <24 hours); 7.6% and 0.9%, respectively, were severe (ie, resulted in participation restriction time >3 weeks). The proportion of hip/groin injuries that were NTL injuries was greater in women than in men (IPR, 1.28; 95% CI, 1.11-1.48). Conversely, the proportion of hip/groin injuries that were severe was greater in men than in women (IPR, 8.67; 95% CI, 1.20-62.73). The most common hip/groin injury diagnosis was strain (men, 67.2%; women, 76.3%). Also, 12 (2.9%) and 3 (2.6%) cases of hip impingement were noted in men's and women's ice hockey, respectively. CONCLUSION: Hip/groin injury rates were greater in men's than in women's ice hockey. Time loss varied between sexes, with men sustaining more injuries with time loss over 3 weeks. Despite increasing concerns of femoroacetabular impingement in ice hockey players, few cases of hip impingement were reported in this dataset. PMID- 26998504 TI - Modification of the Sandwich Estimator in Generalized Estimating Equations with Correlated Binary Outcomes in Rare Event and Small Sample Settings. AB - Regression models for correlated binary outcomes are commonly fit using a Generalized Estimating Equations (GEE) methodology. GEE uses the Liang and Zeger sandwich estimator to produce unbiased standard error estimators for regression coefficients in large sample settings even when the covariance structure is misspecified. The sandwich estimator performs optimally in balanced designs when the number of participants is large, and there are few repeated measurements. The sandwich estimator is not without drawbacks; its asymptotic properties do not hold in small sample settings. In these situations, the sandwich estimator is biased downwards, underestimating the variances. In this project, a modified form for the sandwich estimator is proposed to correct this deficiency. The performance of this new sandwich estimator is compared to the traditional Liang and Zeger estimator as well as alternative forms proposed by Morel, Pan and Mancl and DeRouen. The performance of each estimator was assessed with 95% coverage probabilities for the regression coefficient estimators using simulated data under various combinations of sample sizes and outcome prevalence values with an Independence (IND), Autoregressive (AR) and Compound Symmetry (CS) correlation structure. This research is motivated by investigations involving rare-event outcomes in aviation data. PMID- 26998503 TI - Sex differences in the MB49 syngeneic, murine model of bladder cancer. AB - OBJECTIVE: The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). METHODS: Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro. RESULTS: MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro. CONCLUSIONS: The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice. PMID- 26998506 TI - Collaborating Pathways that Functionally Amplify NOTCH1 Signals in T-Cell Acute Lymphoblastic Leukemia. PMID- 26998505 TI - Outcome measures for Parkinson's disease dementia: a systematic review. AB - BACKGROUND: Parkinson's disease dementia (PDD) is a major cause of morbidity and mortality in Parkinson's disease (PD), which severely affects patient functioning and quality of life and increases the risk for nursing home admission. Unfortunately, current treatment options for PDD are limited and have only marginal therapeutic effects. As novel treatments are developed, there will be a need to assess their efficacy in well-designed randomized controlled trials. However, there is no consensus on the optimal outcome measures for use in PDD clinical trials. METHODS: A systematic review of PDD clinical trials and empiric studies of outcome measures used in PDD was performed. Outcome measures were divided into five categories: 1) cognitive; 2) behavioral and mood; 3) activities of daily living and quality of life; 4) global; and 5) caregiver burden. FINDINGS: A total of 20 PDD pharmacologic clinical trials were identified. These trials incorporated a broad array of outcome measures, which were used inconsistently across trials. We summarize the psychometric properties and other relevant data on outcome measures used, including their diagnostic utility, inter rater reliability, test-retest reliability, responsiveness, clinically meaningful change, and availability of alternate forms. CONCLUSIONS: We have identified the best-evidenced PDD outcome measures in each domain. Further research is needed to assess the validity, reliability, and clinically meaningful change of these measures in PDD to inform the design of future clinical trials and enhance the ability of clinicians, researchers and policy-makers to interpret study results. In addition, the development of outcome measures specific to PDD may be warranted. PMID- 26998507 TI - The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction. AB - Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline. PMID- 26998509 TI - De Novo Transcriptome Sequencing of Olea europaea L. to Identify Genes Involved in the Development of the Pollen Tube. AB - In olive (Olea europaea L.), the processes controlling self-incompatibility are still unclear and the molecular basis underlying this process are still not fully characterized. In order to determine compatibility relationships, using next generation sequencing techniques and a de novo transcriptome assembly strategy, we show that pollen tubes from different olive plants, grown in vitro in a medium containing its own pistil and in combination pollen/pistil from self-sterile and self-fertile cultivars, have a distinct gene expression profile and many of the differentially expressed sequences between the samples fall within gene families involved in the development of the pollen tube, such as lipase, carboxylesterase, pectinesterase, pectin methylesterase, and callose synthase. Moreover, different genes involved in signal transduction, transcription, and growth are overrepresented. The analysis also allowed us to identify members in actin and actin depolymerization factor and fibrin gene family and member of the Ca(2+) binding gene family related to the development and polarization of pollen apical tip. The whole transcriptomic analysis, through the identification of the differentially expressed transcripts set and an extended functional annotation analysis, will lead to a better understanding of the mechanisms of pollen germination and pollen tube growth in the olive. PMID- 26998508 TI - Glycans related to the CA19-9 antigen are elevated in distinct subsets of pancreatic cancers and improve diagnostic accuracy over CA19-9. AB - BACKGROUND AND AIMS: The CA19-9 antigen is the current best biomarker for pancreatic cancer, but it is not elevated in about 25% of pancreatic cancer patients at a cutoff that gives a 25% false-positive rate. We hypothesized that antigens related to the CA19-9 antigen, which is a glycan called sialyl-Lewis A (sLeA), are elevated in distinct subsets of pancreatic cancers. METHODS: We profiled the levels of multiple glycans and mucin glycoforms in plasma from 200 subjects with either pancreatic cancer or benign pancreatic disease, and we validated selected findings in additional cohorts of 116 and 100 subjects, the latter run blinded and including cancers that exclusively were early-stage. RESULTS: We found significant elevations in two glycans: an isomer of sLeA called sialyl-Lewis X, present both in sulfated and non-sulfated forms; and the sialylated form of a marker for pluripotent stem cells, type 1 N-acetyl lactosamine. The glycans performed as well as sLeA as individual markers and were elevated in distinct groups of patients, resulting in a 3-marker panel that significantly improved upon any individual biomarker. The panel gave 85% sensitivity and 90% specificity in the combined discovery and validation cohorts, relative to 54% sensitivity and 86% specificity for sLeA; and it gave 80% sensitivity and 84% specificity in the independent test cohort, as opposed to 66% sensitivity and 72% specificity for sLeA. CONCLUSIONS: Glycans related to sLeA are elevated in distinct subsets of pancreatic cancers and yield improved diagnostic accuracy over CA19-9. PMID- 26998510 TI - High-Volume Transanal Surgery with CPH34 HV for the Treatment of III-IV Degree Haemorrhoids: Final Short-Term Results of an Italian Multicenter Clinical Study. AB - The clinical chart of 621 patients with III-IV haemorrhoids undergoing Stapled Hemorrhoidopexy (SH) with CPH34 HV in 2012-2014 was consecutively reviewed to assess its safety and efficacy after at least 12 months of follow-up. Mean volume of prolapsectomy was significantly higher (13.0 mL; SD, 1.4) in larger prolapse (9.3 mL; SD, 1.2) (p < 0.001). Residual or recurrent haemorrhoids occurred in 11 of 621 patients (1.8%) and in 12 of 581 patients (1.9%), respectively. Relapse was correlated with higher preoperative Constipation Scoring System (CSS) (p = 0.000), Pescatori's degree (p = 0.000), Goligher's grade (p = 0.003), prolapse exceeding half of the length of the Circular Anal Dilator (CAD) (p = 0.000), and higher volume of prolapsectomy (p = 0.000). At regression analysis, only the preoperative CSS, Pescatori's degree, Goligher's grade, and volume of resection were significantly predictive of relapse. A high level of satisfaction (VAS = 8.6; SD, 1.0) coupled with a reduction of 12-month CSS (Delta preoperative CSS/12 mo CSS = 3.4, SD, 2.0; p < 0.001) was observed. The wider prolapsectomy achievable with CPH34 HV determined an overall 3.7% relapse rate in patients with high prevalence of large internal rectal prolapse, coupled with high satisfaction index, significant reduction of CSS, and very low complication rates. PMID- 26998512 TI - An autophagy-independent function for Beclin 1 in cancer. AB - The involvement of Beclin 1 in cancer has been attributed primarily to its role in autophagy initiation. Our recent findings identify a novel, alternative mechanism by which Beclin 1 can impact tumor progression, through the regulation of growth factor receptor signaling. PMID- 26998511 TI - Regenerative Engineering of Cartilage Using Adipose-Derived Stem Cells. AB - Injury to the articular cartilage occurs commonly in the general population and undergoes minimal spontaneous healing. Traditional methods of cartilage repair provide no long-term cure and are significant causes of morbidity. For this reason, stem cell therapies have recently been investigated for their ability to regenerate cartilage, and the results have been promising. Since the discovery that adipose tissue is a major source of mesenchymal stem cells in 2001, scientists have been studying the use of adipose-derived stem cells (ASCs) for the treatment of various disorders including lesions of the articular cartilage. ASCs hold several advantages over autologous chondrocytes for cartilage repair, including but not limited to their anti-inflammatory effects, their multi-lineage differentiation potential, and their ability to form new cartilage in a defect. Whereas several investigations have been made in in vitro and animal models, there have been surprisingly little clinical studies on the intra-articular use of adipose-derived stem cells, despite their first isolation about a decade and a half ago. The few studies that have been conducted are encouraging. With approval for various stem cell therapies on the horizon, this review seeks to update the clinician and the researcher on the current state-of-the-art use of adipose derived stem cells for the treatment of cartilage disorders and the regenerative engineering of cartilaginous tissue. PMID- 26998513 TI - Editorial: A Message from the Editor-in-Chief. PMID- 26998514 TI - Identification of "Preferred" Human Kinase Inhibitors for Sleeping Sickness Lead Discovery. Are Some Kinases Better than Others for Inhibitor Repurposing? AB - A kinase-targeting cell-based high-throughput screen (HTS) against Trypanosoma brucei was recently reported, and this screening set included the Published Kinase Inhibitor Set (PKIS). From the PKIS was identified 53 compounds with pEC50 >= 6. Utilizing the published data available for the PKIS, a statistical analysis of these active antiparasitic compounds was performed, allowing identification of a set of human kinases having inhibitors that show a high likelihood for blocking T. brucei cellular proliferation in vitro. This observation was confirmed by testing other established inhibitors of these human kinases and by mining past screening campaigns at GlaxoSmithKline. Overall, although the parasite targets of action are not known, inhibitors of this set of human kinases displayed an enhanced hit rate relative to a random kinase-targeting HTS campaign, suggesting that repurposing efforts should focus primarily on inhibitors of these specific human kinases. We therefore term this statistical analysis-driven approach "preferred lead repurposing". PMID- 26998517 TI - Resolving enantiomers using the optical angular momentum of twisted light. AB - Circular dichroism and optical rotation are crucial for the characterization of chiral molecules and are of importance to the study of pharmaceutical drugs, proteins, DNA, and many others. These techniques are based on the different interactions of enantiomers with circularly polarized components of plane wave light that carries spin angular momentum (SAM). For light carrying orbital angular momentum (OAM), for example, twisted or helical light, the consensus is that it cannot engage with the chirality of a molecular system as previous studies failed to demonstrate an interaction between optical OAM and chiral molecules. Using unique nanoparticle aggregates, we prove that optical OAM can engage with materials' chirality and discriminate between enantiomers. Further, theoretical results show that compared to circular dichroism, mainly based on magnetic dipole contributions, the OAM analog helical dichroism (HD) is critically dependent on fundamentally different chiral electric quadrupole contributions. Our work opens new venues to study chirality and can find application in sensing and chiral spectroscopy. PMID- 26998515 TI - Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy. AB - Deleterious inflammation is a primary feature of breast cancer. Accumulating evidence demonstrates that macrophages, the most abundant leukocyte population in mammary tumors, have a critical role at each stage of cancer progression. Such tumor-associated macrophages facilitate neoplastic transformation, tumor immune evasion and the subsequent metastatic cascade. Herein, we discuss the dynamic process whereby molecular and cellular features of the tumor microenvironment act to license tissue-repair mechanisms of macrophages, fostering angiogenesis, metastasis and the support of cancer stem cells. We illustrate how tumors induce, then exploit trophic macrophages to subvert innate and adaptive immune responses capable of destroying malignant cells. Finally, we discuss compelling evidence from murine models of cancer and early clinical trials in support of macrophage targeted intervention strategies with the potential to dramatically reduce breast cancer morbidity and mortality. PMID- 26998516 TI - Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly. AB - The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures. To study these organizational stratifications, we perturb a key hinge region by expressing an exon that is universally spliced out in human tropoelastins. We find a herniated nanostructure with a displaced C terminus and explain by molecular modeling that flexible helices are replaced with substantial beta sheets. We see atypical higher-order cross-linking and inefficient assembly into discontinuous, thick elastic fibers. We explain this dysfunction by correlating local and global structural effects with changes in the molecule's assembly dynamics. This work has general implications for our understanding of elastomeric proteins, which balance disordered regions with defined structural modules at multiple scales for functional assembly. PMID- 26998518 TI - Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting. AB - High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion-the intraclonal diversity index-which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology. PMID- 26998519 TI - Experimental test of Landauer's principle in single-bit operations on nanomagnetic memory bits. AB - Minimizing energy dissipation has emerged as the key challenge in continuing to scale the performance of digital computers. The question of whether there exists a fundamental lower limit to the energy required for digital operations is therefore of great interest. A well-known theoretical result put forward by Landauer states that any irreversible single-bit operation on a physical memory element in contact with a heat bath at a temperature T requires at least k B T ln(2) of heat be dissipated from the memory into the environment, where k B is the Boltzmann constant. We report an experimental investigation of the intrinsic energy loss of an adiabatic single-bit reset operation using nanoscale magnetic memory bits, by far the most ubiquitous digital storage technology in use today. Through sensitive, high-precision magnetometry measurements, we observed that the amount of dissipated energy in this process is consistent (within 2 SDs of experimental uncertainty) with the Landauer limit. This result reinforces the connection between "information thermodynamics" and physical systems and also provides a foundation for the development of practical information processing technologies that approach the fundamental limit of energy dissipation. The significance of the result includes insightful direction for future development of information technology. PMID- 26998520 TI - Designing durable icephobic surfaces. AB - Ice accretion has a negative impact on critical infrastructure, as well as a range of commercial and residential activities. Icephobic surfaces are defined by an ice adhesion strength tauice < 100 kPa. However, the passive removal of ice requires much lower values of tauice, such as on airplane wings or power lines (tauice < 20 kPa). Such low tauice values are scarcely reported, and robust coatings that maintain these low values have not been reported previously. We show that, irrespective of material chemistry, by tailoring the cross-link density of different elastomeric coatings and by enabling interfacial slippage, it is possible to systematically design coatings with extremely low ice adhesion (tauice < 0.2 kPa). These newfound mechanisms allow for the rational design of icephobic coatings with virtually any desired ice adhesion strength. By using these mechanisms, we fabricate extremely durable coatings that maintain tauice < 10 kPa after severe mechanical abrasion, acid/base exposure, 100 icing/deicing cycles, thermal cycling, accelerated corrosion, and exposure to Michigan wintery conditions over several months. PMID- 26998521 TI - Single-plasmon interferences. AB - Surface plasmon polaritons are electromagnetic waves coupled to collective electron oscillations propagating along metal-dielectric interfaces, exhibiting a bosonic character. Recent experiments involving surface plasmons guided by wires or stripes allowed the reproduction of quantum optics effects, such as antibunching with a single surface plasmon state, coalescence with a two-plasmon state, conservation of squeezing, or entanglement through plasmonic channels. We report the first direct demonstration of the wave-particle duality for a single surface plasmon freely propagating along a planar metal-air interface. We develop a platform that enables two complementary experiments, one revealing the particle behavior of the single-plasmon state through antibunching, and the other one where the interferences prove its wave nature. This result opens up new ways to exploit quantum conversion effects between different bosonic species as shown here with photons and polaritons. PMID- 26998522 TI - Low-temperature plasticity of olivine revisited with in situ TEM nanomechanical testing. AB - The rheology of the lithospheric mantle is fundamental to understanding how mantle convection couples with plate tectonics. However, olivine rheology at lithospheric conditions is still poorly understood because experiments are difficult in this temperature range where rocks and mineral become very brittle. We combine techniques of quantitative in situ tensile testing in a transmission electron microscope and numerical modeling of dislocation dynamics to constrain the low-temperature rheology of olivine. We find that the intrinsic ductility of olivine at low temperature is significantly lower than previously reported values, which were obtained under strain-hardened conditions. Using this method, we can anchor rheological laws determined at higher temperature and can provide a better constraint on intermediate temperatures relevant for the lithosphere. More generally, we demonstrate the possibility of characterizing the mechanical properties of specimens, which can be available in the form of submillimeter sized particles only. PMID- 26998523 TI - MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer? AB - Colorectal cancer (CRC) is one of the most common malignancies and is associated closely with inflammation before and after development. Macrophages promote colitis and colitis-associated CRC. M1 macrophages contribute to colitis directly through the production of proinflammatory cytokines and through activation of proinflammatory immune cell phenotypes. In cancer, both M1 and M2 macrophages participate in tumor development and progression through cytokine production, changes in cell signaling and activation of T cells. We have identified the mitogen-activated protein kinase-activated protein kinase 2 (MK2) as a regulator of macrophages during colitis-associated CRC (CAC). MK2 is a proinflammatory kinase that promotes production of IL-1alpha, IL-1beta, IL-6 and TNF-alpha. MK2-/ mice have decreases in macrophages, macrophage-associated chemokines, and proinflammatory cytokines. Most significantly, MK2-/- mice do not develop neoplasms in an inflammatory model of CRC. However, addition of MK2+/+ macrophages to MK2-/- mice increases production of proinflammatory cytokines. In wild type mice, both cytokines and tumor burdens increase upon addition of additional macrophages. These data support the importance of MK2 in macrophage regulation during inflammation-associated CRC. PMID- 26998524 TI - Mitochondrial protein hyperacetylation in the failing heart. AB - Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothesized that accumulation of metabolite intermediates of fuel oxidation pathways drives posttranslational modifications of mitochondrial proteins during the development of heart failure. Myocardial acetylproteomics demonstrated extensive mitochondrial protein lysine hyperacetylation in the early stages of heart failure in well-defined mouse models and the in end-stage failing human heart. To determine the functional impact of increased mitochondrial protein acetylation, we focused on succinate dehydrogenase A (SDHA), a critical component of both the tricarboxylic acid (TCA) cycle and respiratory complex II. An acetyl-mimetic mutation targeting an SDHA lysine residue shown to be hyperacetylated in the failing human heart reduced catalytic function and reduced complex II-driven respiration. These results identify alterations in mitochondrial acetyl-CoA homeostasis as a potential driver of the development of energy metabolic derangements that contribute to heart failure. PMID- 26998526 TI - The Urinary Uric Acid/Creatinine Ratio is An Adjuvant Marker for Perinatal Asphyxia. AB - OBJECTIVE: To assess the urinary uric acid/creatinine ratio (UA/Cr) in relation to Apgar score and cord blood gas analysis in identification of perinatal asphyxia and to define the cutoff values. DESIGN: case control study. SETTING: The newborns admitted in the department of pediatrics and NICU of Mediciti Institute of Medical Science, Ghanpur, Medchal mandal, Telangana from May-July 2011 were enrolled. PARTICIPANTS/PATIENTS: The study was conducted on 31 (18 males, 13 females) controls and 18 (12males, 6 females) asphyxiated neonates. OUTCOME MEASURES: 5ml of arterial cord blood of newborn collected at the time of birth and spot urine samples were collected within 24-72 hours of life. Cord blood gas analysis were done immediately and Urinary uric acid was measured by modified Uricase method, urinary creatinine by modified kinetic Jaffe's reaction. RESULTS: The mean urinary uric acid and creatinine ratio (2.58+/- 0.48 vs 1.89 +/ 0.59) is significantly higher in Asphyxiated group than in the control group. The umbilical cord blood pH had significant positive correlation with 1st minute Apgar score (r= 0.41, p=0.003), 5th minute Apgar (r= 0.44, p=0.002), while urinary UA/Cr ratio had significant negative correlation with cord blood pH (r= 0.63, p=0.002). Urinary UA/Cr ratio with criterion of >2.43 had 80% sensitivity, 87.5% specificity with AUC of 0.84 (p=0.003) had a better predictive value. CONCLUSIONS: Urinary UA/Cr ratio is easy, non-invasive, painless and economical adjuvant parameter with better predictive value for diagnosing perinatal asphyxia with simple diagnostic equipment. PMID- 26998525 TI - Cell Differentiation and Checkpoint. AB - DNA damage is induced in many types of cells by internal and external cell stress. When DNA is damaged, DNA Damage Response (DDR) programs are activated to repair the DNA lesions in order to preserve genomic integrity and suppress subsequent malignant transformation. Among these programs is cell cycle checkpoint that ensures cell cycle arrest and subsequent repair of the damaged DNA, apoptosis and senescence in various phases of the cell cycle. Moreover, recent studies have established the cell differentiation checkpoint, the other type of the checkpoint that is specifically activated in the course of differentiation. We will discuss the evidences that support the link between DNA damage proteins and C2C12 cell differentiation. PMID- 26998527 TI - Magnetic Resonance Imaging of Cerebral Blood Flow in Animal Stroke Models. AB - Perfusion could provide useful information on metabolic and functional status of tissue and organs. This review summarizes the most commonly used perfusion measurement methods: dynamic susceptibility weighted contrast (DSC) and arterial spin labeling (ASL) and their applications in experimental stroke. Some new developments of CBF techniques in animal models are also discussed. PMID- 26998528 TI - Structure of Periodic Crystals and Quasicrystals in Ultrathin Films of Ba-Ti-O. AB - We model the remarkable thin-film Ba-Ti-O structures formed by heat treatment of an initial perovskite BaTiO3 thin film on a Pt(111) surface. All structures contain a rumpled Ti-O network with all Ti threefold coordinated with O, and with Ba occupying the larger. mainly Ti7O7, pores. The quasicrystal structue is a simple decoration of three types of tiles: square, triangle and 30 degrees rhombus, with edge lengths 6.85 A, joined edge-to-edge in a quasicrystalline pattern; observed periodic crystals in ultrathin film Ba-Ti-O are built from these and other tiles. Simulated STM images reproduce the patterns seen experimentally, and identify the bright protrusions as Ba atoms. The models are consistent with all experimental observations. PMID- 26998530 TI - Trend and Network Analysis of Common Eligibility Features for Cancer Trials in ClinicalTrials.gov. AB - ClinicalTrials.gov has been archiving clinical trials since 1999, with > 165,000 trials at present. It is a valuable but relatively untapped resource for understanding trial design patterns and acquiring reusable trial design knowledge. We extracted common eligibility features using an unsupervised tag mining method and mined their temporal usage patterns in clinical trials on various cancers. We then employed trend and network analysis to investigate two questions: (1) what eligibility features are frequently used to select patients for clinical trials within one cancer or across multiple cancers; and (2) what are the trends in eligibility feature adoption or discontinuation across cancer research domains? Our results showed that each cancer domain reuses a small set of eligibility features frequently for selecting cancer trial patients and some features are shared across different cancers, with value range adjustments for numerical measures. We discuss the implications for facilitating community-based clinical research knowledge sharing and reuse. PMID- 26998531 TI - A quinone mediator drives oxidations catalysed by alcohol dehydrogenase containing cell lysates. AB - Spontaneous electron transport to molecular oxygen led to regeneration of oxidised nicotinamide cofactor in cell lysates that contain an alcohol dehydrogenase, a quinone reductase and a quinone mediator. This concept allows the efficient oxidation of alcohols in the presence of alcohol dehydrogenase containing E. coli lysates and catalytic amounts of the quinone lawsone. PMID- 26998532 TI - Cooperative catalysis for the direct hydrodeoxygenation of vegetable oils into diesel-range alkanes over Pd/NbOPO4. AB - Near quantitative carbon yields of diesel-range alkanes were achieved from the hydrodeoxygenation of triglycerides over Pd/NbOPO4 under mild conditions with no catalyst deactivation: catalyst characterization and theoretical calculations suggest that the high hydrodeoxygenation activity originated from the synergistic effect of Pd and strong Lewis acidity on the unique structure of NbOPO4. PMID- 26998529 TI - Perils of Pragmatic Psychiatry: How We Can Do Better. AB - Etiologic and pathophysiologic understanding of psychiatric disorders is still in its early stages. The neurobiology of major psychiatric disorders has yet to be fully elucidated. Psychiatric diagnoses are often based on presenting symptoms, lacking reliability and stability. For a variety of reasons, many notable laboratory and clinical observations have not been tested in large trials. Lacking this validation, these potentially valuable practices have not been widely disseminated nor translated into real world practice. Pragmatic practice today requires optimum use of the available resources. This may sometimes require translating novel treatments supported by strong, evidence-based, level II evidence; but still lacking level I evidence into practice and greater utilization of evidence-based approved practices. The purpose of this paper is to highlight some common avoidable pitfalls in practice, and to offer a few psychopharmacological pearls. PMID- 26998533 TI - An enzyme-responsive controlled release system based on a dual-functional peptide. AB - A new controlled release system was developed by loading a dual-functional peptide (DFP) on a mesoporous silica material. One-pot synthesis produced a DFP that was stimuli responsive, releasing a therapeutic peptide by protease cleavage. The design provides new steps towards smart biomaterials. PMID- 26998534 TI - Design of a hydrophobic tripeptide that self-assembles into amphiphilic superstructures forming a hydrogel biomaterial. AB - We report the rational design of a heterochiral hydrophobic tripeptide self assembling into amphiphilic d-superstructures that yield a self-supportive hydrogel at physiological pH. The material endures cell culture conditions and sustains fibroblast proliferation. Tripeptide superstructures are thoroughly analysed by several techniques. PMID- 26998535 TI - Coupling a DNA-ligand ensemble with Ag cluster formation for the label-free and ratiometric detection of intracellular biothiols. AB - We have demonstrated the synthesis of a smart nanoprobe by coupling a DNA-ligand ensemble with Ag cluster formation that allows the label-free and ratiometric detection of intracellular biothiols with high sensitivity and selectivity as well as discrimination of normal cells and cancer cells. PMID- 26998536 TI - Comparative kinetic and energetic modelling of phyllosemiquinone oxidation in Photosystem I. AB - The oxidation kinetics of phyllo(semi)quinone (PhQ), which acts as an electron transfer (ET) intermediate in the Photosystem I reaction centre, are described by a minimum of two exponential phases, characterised by lifetimes in the 10-30 ns and 150-300 ns ranges. The fastest phase is considered to be dominated by the oxidation of the PhQ molecule coordinated by the PsaB reaction centre subunit (PhQB), and the slowest phase is dominated by the oxidation of the PsaA coordinated PhQ (PhQA). Testing different energetic schemes within a unified theory-based kinetic modelling approach provides reliable limit-values for some of the physical-chemical parameters controlling these ET reactions: (i) the value of DeltaG(0) associated with PhQA oxidation is smaller than ~+30 meV; (ii) the value of the total reorganisation energy (lambdat) likely exceeds 0.7 eV; (iii) different mean nuclear modes are coupled to PhQB and PhQA oxidation, the former being larger, and both being >=100 cm(-1). PMID- 26998537 TI - Facile labelling of graphene oxide for superior capacitive energy storage and fluorescence applications. AB - The majority of supercapacitor research studies on graphene materials today have been based upon developing electrochemical double-layer capacitors (EDLCs) using reduced graphenes. In contrast, graphene oxide (GO) is often neglected as a supercapacitor candidate due to its low electrical conductivity and surface area. Nonetheless, we present herein a fast (1 h) labelling of GO with o phenylenediamine (PD) to produce PD-GO, exploiting inherent oxygen groups in creating new functionalities that exhibit capacitive enhancement from pseudo capacitance. A high specific capacitance of 191 F g(-1) was obtained (at 0.2 A g( 1)), comparable to recent binder-free graphene supercapacitors. The large surface normalized capacitance of up to 628 MUF cm(-2) is also many times greater than the intrinsic capacitance of single-layer graphene (21 MUF cm(-2)) as a result of additional pseudo-capacitance. A high capacity retention of ~85% with each 10 fold increase in current density further indicates excellent rate performance. Hence, this approach in enhancing GO pseudo-capacitance may be similarly feasible as graphene EDLCs. Additionally, PD-GO was also found to exhibit a bright green fluorescence with a 540 nm maximum. The strongest fluorescence intensities arose from the smallest PD-GO fragments, and we attribute the origin to localised sp(2) domains and newly formed phenazine edge groups. The dual enhancement of dissimilar properties such as capacitance and fluorescence emphasizes the continued significance of covalent functionalisation towards tuning of properties in graphene-type materials. PMID- 26998538 TI - [Processed foods: an important cause of obesity]. PMID- 26998539 TI - [Hello health mobile application]. PMID- 26998540 TI - [Learning situations!]. PMID- 26998541 TI - [Subway, work, sleep]. PMID- 26998542 TI - [Access to cancer medications. Quebec is behind schedule]. PMID- 26998543 TI - [Cellular phones and radiofrequencies]. PMID- 26998544 TI - [Alzheimer disease. Fat droplets in the brain: new avenues for research]. PMID- 26998545 TI - [Medication or meditation?]. PMID- 26998546 TI - [Bisphosphonates]. PMID- 26998547 TI - [Clarithromycin and certain statins]. PMID- 26998548 TI - [Myths and realities. Sexually transmitted diseases in the older generation]. PMID- 26998549 TI - Unusual Recognition and Separation of Hydrated Metal Sulfates [M2(MU-SO4)2(H2O)n, M = Zn(II), Cd(II), Co(II), Mn(II)] by a Ditopic Receptor. AB - A ditopic receptor L1, having metal binding bis(2-picolyl) donor and anion binding urea group, is synthesized and explored toward metal sulfate recognition via formation of dinuclear assembly, (L1)2M2(SO4)2. Mass spectrometric analysis, (1)H-DOSY NMR, and crystal structure analysis reveal the existence of a dinuclear assembly of MSO4 with two units of L1. (1)H NMR study reveals significant downfield chemical shift of -NH protons of urea moiety of L1 selectively with metal sulfates (e.g., ZnSO4, CdSO4) due to second-sphere interactions of sulfate with the urea moiety. Variable-temperature (1)H NMR studies suggest the presence of intramolecular hydrogen bonding interaction toward metal sulfate recognition in solution state, whereas intermolecular H-bonding interactions are observed in solid state. In contrast, anions in their tetrabutylammonium salts fail to interact with the urea -NH probably due to poor acidity of the tertiary butyl urea group of L1. Metal sulfate binding selectivity in solution is further supported by isothermal titration calorimetric studies of L1 with different Zn salts in dimethyl sulfoxide (DMSO), where a binding affinity is observed for ZnSO4 (Ka = 1.23 * 10(6)), which is 30- to 50-fold higher than other Zn salts having other counteranions in DMSO. Sulfate salts of Cd(II)/Co(II) also exhibit binding constants in the order of ~1 * 10(6) as in the case of ZnSO4. Positive role of the urea unit in the selectivity is confirmed by studying a model ligand L2, which is devoid of anion recognition urea unit. Structural characterization of four MSO4 [M = Zn(II), Cd(II), Co(II), Mn(II)] complexes of L1, that is, complex 1, [(L1)2(Zn)2(MU-SO4)2]; complex 2, [(L1)2(H2O)2(Cd)2(MU-SO4)2]; complex 3, [(L1)2(H2O)2(Co)2(MU-SO4)2]; and complex 4, [(L1)2(H2O)2(Mn)2(MU-SO4)2], reveal the formation of sulfate-bridged eight-membered crownlike binuclear complexes, similar to one of the concentration-dependent dimeric forms of MSO4 as observed in solid state. Finally, L1 is found to be highly efficient in removing ZnSO4 from both aqueous and semiaqueous medium as complex 1 in the presence of other competing Zn(II) salts via precipitation through crystallization. Powder X ray diffraction analysis has also confirmed bulk purity of complex 1 obtained from the above competitive crystallization experiment. PMID- 26998551 TI - Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities. AB - The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management. PMID- 26998550 TI - Silver as Seed-Particle Material for GaAs Nanowires--Dictating Crystal Phase and Growth Direction by Substrate Orientation. AB - Here we investigate the feasibility of silver as seed-particle material to synthesize GaAs nanowires and show that both crystal phase and growth direction can be controlled by choice of substrate orientation. A (111)B substrate orientation can be used to form vertically aligned wurtzite GaAs nanowires and a (100) substrate orientation to form vertically aligned zinc blende GaAs nanowires. A 45-50% yield of vertical nanowire growth is achieved on the (100) substrate orientation without employing any type of surface modification or nucleation strategy to promote a vertical growth direction. In addition, photoluminescence measurements reveal that the photon emission from the silver seeded wurtzite GaAs nanowires is characterized by a single and narrow emission peak at 1.52 eV. PMID- 26998553 TI - Correction to Study of RNA Polymerase II Clustering inside Live-Cell Nuclei Using Bayesian Nanoscopy. PMID- 26998552 TI - Redox Capacity of an Extracellular Matrix Protein Associated with Adhesion in Mytilus californianus. AB - Adhesive mussel foot proteins (Mfps) rely in part on DOPA (3,4-dihydroxyphenyl-l alanine) side chains to mediate attachment to mineral surfaces underwater. Oxidation of DOPA to Dopaquinone (Q) effectively abolishes the adsorption of Mfps to these surfaces. The thiol-rich mussel foot protein-6 (Mfp-6) rescues adhesion compromised by adventitious DOPA oxidation by reducing Q back to DOPA. The redox chemistry and kinetics of foot-extracted Mfp-6 were investigated by using a nonspecific chromogenic probe to equilibrate with the redox pool. Foot-extracted Mfp-6 has a reducing capacity of ~17 e(-) per protein; half of this comes from the cysteine residues, whereas the other half comes from other constituents, probably a cohort of four or five nonadhesive, redox-active DOPA residues in Mfp 6 with an anodic peak potential ~500 mV lower than that for oxidation of cysteine to cystine. At higher pH, DOPA redox reversibility is lost possibly due to Q scavenging by Cys thiolates. Analysis by one- and two-dimensional proton nuclear magnetic resonance identified a pronounced beta-sheet structure with a hydrophobic core in foot-extracted Mfp-6 protein. The structure endows redox active side chains in Mfp-6, i.e., cysteine and DOPA, with significant reducing power over a broad pH range, and this power is measurably diminished in recombinant Mfp-6. PMID- 26998554 TI - Solar Hydrogen Production Using Molecular Catalysts Immobilized on Gallium Phosphide (111)A and (111)B Polymer-Modified Photocathodes. AB - We report the immobilization of hydrogen-producing cobaloxime catalysts onto p type gallium phosphide (111)A and (111)B substrates via coordination to a surface grafted polyvinylimidazole brush. Successful grafting of the polymeric interface and subsequent assembly of cobalt-containing catalysts are confirmed using grazing angle attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Photoelectrochemical testing in aqueous conditions at neutral pH shows that cobaloxime modification of either crystal face yields a similar enhancement of photoperformance, achieving a greater than 4 fold increase in current density and associated rates of hydrogen production as compared to results obtained using unfunctionalized electrodes tested under otherwise identical conditions. Under simulated solar illumination (100 mW cm( 2)), the catalyst-modified photocathodes achieve a current density ~ 1 mA cm(-2) when polarized at 0 V vs the reversible hydrogen electrode reference and show near-unity Faradaic efficiency for hydrogen production as determined by gas chromatography analysis of the headspace. This work illustrates the modularity and versatility of the catalyst-polymer-semiconductor approach for directly coupling light harvesting to fuel production and the ability to export this chemistry across distinct crystal face orientations. PMID- 26998555 TI - Effects of Chemical Conjugation of l-Leucine to Chitosan on Dispersibility and Controlled Release of Drug from a Nanoparticulate Dry Powder Inhaler Formulation. AB - This study investigated l-leucine-conjugated chitosan as a drug delivery vehicle in terms of dispersibility and controlled release from a nanoparticulate dry powder inhaler (DPI) formulation for pulmonary delivery using diltiazem hydrochloride (DH) as the model drug. DH-loaded nanoparticles of chitosan and conjugate were prepared by water-in-oil emulsification followed by glutaraldehyde cross-linking. Nanoparticles were characterized by dynamic light scattering for particle size, X-ray photoelectron spectroscopy for surface composition, and twin stage impinger for drug dispersibility. The controlled release of DH was studied in phosphate-buffered saline (pH 7.3 +/- 0.2, 37 degrees C) using UV spectrophotometry. The fine particle fractions of conjugated chitosan with and without drug were higher than those of nonconjugated chitosan nanoparticles. The conjugate nanoparticles were superior to those of unmodified chitosan in drug loading, entrapment efficiency, and controlled release profile. The higher dispersibility was attributed to the amphiphilic environment of the l-leucine conjugate and hydrophobic cross-links, and the release profile reflects the greater swelling. The conjugated chitosan nanoparticles could be useful, after appropriate testing for biodegradability and toxicity, as an alternative carrier for lung drug delivery with enhanced aerosolization and prolonged drug release from nanoparticulate DPI formulations. PMID- 26998556 TI - Pediatric Musculoskeletal Ultrasound: Practical Imaging Approach. AB - OBJECTIVE: The purpose of this article is to review some of the common indications for pediatric musculoskeletal ultrasound examination, with emphasis given to imaging technique, normal anatomy, and the spectrum of pathologic findings seen in the pediatric population. CONCLUSION: Ultrasound is an essential first-line tool in pediatric musculoskeletal imaging. It aids in determining which patients may benefit from further imaging, including radiography, CT, and MRI. PMID- 26998557 TI - Antimicrobial Peptide from the Wild Bee Hylaeus signatus Venom and Its Analogues: Structure-Activity Study and Synergistic Effect with Antibiotics. AB - Venoms of hymenopteran insects have attracted considerable interest as a source of cationic antimicrobial peptides (AMPs). In the venom of the solitary bee Hylaeus signatus (Hymenoptera: Colletidae), we identified a new hexadecapeptide of sequence Gly-Ile-Met-Ser-Ser-Leu-Met-Lys-Lys-Leu-Ala-Ala-His-Ile-Ala-Lys-NH2. Named HYL, it belongs to the category of alpha-helical amphipathic AMPs. HYL exhibited weak antimicrobial activity against several strains of pathogenic bacteria and moderate activity against Candida albicans, but its hemolytic activity against human red blood cells was low. We prepared a set of HYL analogues to evaluate the effects of structural modifications on its biological activity and to increase its potency against pathogenic bacteria. This produced several analogues exhibiting significantly greater activity compared to HYL against strains of both Staphylococcus aureus and Pseudomonas aeruginosa even as their hemolytic activity remained low. Studying synergism of HYL peptides and conventional antibiotics showed the peptides act synergistically and preferentially in combination with rifampicin. Fluorescent dye propidium iodide uptake showed the tested peptides were able to facilitate entrance of antibiotics into the cytoplasm by permeabilization of the outer and inner bacterial cell membrane of P. aeruginosa. Transmission electron microscopy revealed that treatment of P. aeruginosa with one of the HYL analogues caused total disintegration of bacterial cells. NMR spectroscopy was used to elucidate the structure-activity relationship for the effect of amino acid residue substitution in HYL. PMID- 26998559 TI - Protective activity of an anthocyanin-rich extract from bilberries and blackcurrants on acute acetaminophen-induced hepatotoxicity in rats. AB - Acetaminophen (N-acetyl-p-aminophenol, APAP) overdosage can produce fatal centrilobular hepatic necrosis in humans. The present study attempted to investigate the protective effect of an anthocyanin-rich extract from bilberries and blackcurrants (AE) against APAP-induced acute hepatic damage in rats. Treatment with AE normalised blood activities of glutamate oxaloacetate and glutamate pyruvate transaminase and prevented APAP-induced plasmatic and tissutal alterations in biomarkers of oxidative stress, probably due to various bioproperties of the components of the extract. PMID- 26998558 TI - Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats. AB - The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 min of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-h intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-min to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similar attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress. PMID- 26998560 TI - The rapid-chase theory does not extend to movement execution. AB - It is assumed that the processing of a prime followed by a mask occurs sequentially in a feedforward manner when the three (initiation, takeover, and independence) criteria outlined by the rapid-chase theory are met. The purpose of the current study was to determine if the processing of the prime and mask fit the predictions of the rapid-chase theory when the prime and mask are presented during an ongoing movement. In two experiments, participants made rapid pointing movements to a target indicated by the mask. In Experiment 1, the prime was presented at movement onset and the prime-mask stimulus onset asynchrony (SOA) was manipulated. In Experiment 2, the prime-mask SOA was constant but the delay between movement and prime onset was manipulated. Although the results support the initiation and takeover criteria, the data did not support the independence criterion. Consequently, the rapid-chase theory does not appear to extend to movement execution. PMID- 26998561 TI - Only pre-cueing but no retro-cueing effects emerge with masked arrow cues. AB - The impact of masked stimulation on cognitive control processes is investigated with much interest. In many cases, masked stimulation suffices to initiate and employ control processes. Shifts of attention either happen in the external environment or internally, for example, in working memory. In the former, even masked cues (i.e., cues that are presented for a period too short to allow strategic use) were shown efficient for shifting attention to particular locations in pre-cue paradigms. Internal attention shifting can be investigated using retro-cues: long after encoding, a valid cue indicates the location to-be tested via change detection, and this improves performance (retro-cue effect). In the present experiment, participants performed in both a pre- and a retro-cue task with masked and normally presented cues. While the masked cues benefitted performance in the pre-cue task, they did not in the retro-cue task. These results inform about limits of masked stimulation. PMID- 26998563 TI - Imagining the future: A cross-cultural perspective on possible selves. AB - This study examined the impact of culture on the qualitative and quantitative features of possible selves. Young adults from Turkey (n=55), Serbia (n=64), and the United Kingdom (n=73) generated images of eight possible selves (e.g. I will be a doctor) which were dated and rated for vividness, positivity, imagery perspective, rehearsal, and according to whether or not they involved other people. All possible selves were coded according to categories (e.g. job, parenthood, self-improvement). There were cross-cultural differences in the types of possible selves generated and in the ratings for vividness, positivity, and rehearsal. Across all three cultures, specific possible selves were more frequently generated than abstract possible selves. Specific possible selves were rated as significantly more vivid and were dated as emerging later than abstract possible selves. Results are discussed with reference to cultural life scripts and the effects of culture on future cognitions. PMID- 26998562 TI - Intentional action processing results from automatic bottom-up attention: An EEG investigation into the Social Relevance Hypothesis using hypnosis. AB - Social stimuli grab our attention. However, it has rarely been investigated how variations in attention affect the processing of social stimuli, although the answer could help us uncover details of social cognition processes such as action understanding. In the present study, we examined how changes to bottom-up attention affects neural EEG-responses associated with intentional action processing. We induced an increase in bottom-up attention by using hypnosis. We recorded the electroencephalographic MU-wave suppression of hypnotized participants when presented with intentional actions in first and third person perspective in a video-clip paradigm. Previous studies have shown that the MU rhythm is selectively suppressed both when executing and observing goal-directed motor actions; hence it can be used as a neural signal for intentional action processing. Our results show that neutral hypnotic trance increases MU suppression in highly suggestible participants when they observe intentional actions. This suggests that social action processing is enhanced when bottom-up attentional processes are predominant. Our findings support the Social Relevance Hypothesis, according to which social action processing is a bottom-up driven attentional process, and can thus be altered as a function of bottom-up processing devoted to a social stimulus. PMID- 26998564 TI - Liver Fat Assessed With CT Relates to MRI Markers of Incipient Brain Injury in Middle-Aged to Elderly Overweight Persons. AB - OBJECTIVE: Obesity has been related to structural brain abnormalities. Increasing evidence suggests that accumulation of fat in the liver is an important determinant of cardiometabolic complications of obesity. The purpose of this study was to investigate the association between CT-assessed liver-to-spleen attenuation ratio as a measure of liver steatosis and MRI-assessed brain tissue integrity in middle-aged to elderly persons. SUBJECTS AND METHODS: CT and MRI were performed on 213 participants (114 women, 99 men; mean age, 65 +/- 7 years). Brain tissue integrity was assessed by magnetization transfer imaging. Linear regression analysis was adjusted for age, sex, vascular risk factors, and total body fat estimated from bioelectrical impedance analysis. RESULTS: Seventy-nine participants had normal weight (body mass index [BMI], 18.5-24.9), and 134 were overweight (BMI >= 25). Significant interaction was found between liver-to-spleen ratio and BMI (p = 0.001). In the overweight group, liver fat was associated with reduced brain tissue integrity in both gray matter (standardized beta = 0.22; 95% CI, 0.07-0.36) and white matter (standardized beta = 0.31; 95% CI, 0.15-0.45). These associations were not found in the normal weight group (gray matter standardized beta = -0.08; 95% CI, -0.33 to 0.16; white matter standardized beta = -0.09; 95% CI, -0.36-0.14). CONCLUSION: The results indicate that liver fat assessed with CT relates to MRI markers of incipient brain injury in middle-aged to elderly overweight persons. PMID- 26998565 TI - Diosgenin effectively suppresses skin inflammation induced by phthalic anhydride in IL-4/Luc/CNS-1 transgenic mice. AB - To quantitatively evaluate the therapeutic effects of diosgenin (DG) and investigate the role of IL-4 on skin inflammation, alterations in luciferase derived signal and general phenotype biomarkers were measured in IL-4/Luc/CNS-1 transgenic mice with phthalic anhydride (PA)-induced skin inflammation after treatment with DG for 4 weeks. High levels of luciferase-derived signal detected in the abdominal region and submandibular lymph node (SL) of the PA treated group was significantly decreased by 67-88% in the PA + DG cotreated group. Furthermore, the weight of the lymph node and spleen, IgE concentration, epidermis thickness, and number of infiltrated mast cells were lower in the PA + DG treated group than the PA + Vehicle treated group. Moreover, expression of IL 6 and vascular endothelial growth factor (VEGF) also decreased in the PA + DG cotreated group. These results suggest that PA-induced skin inflammation could be successfully suppressed by DG treatment in IL-4/Luc/CNS-1 Tg mice through attenuation of IL-4 and IL-6 expression, as well as decreased IgE concentration and mast cells infiltration. PMID- 26998566 TI - Using cognitive models to develop quality multiple-choice questions. AB - With the recent interest in competency-based education, educators are being challenged to develop more assessment opportunities. As such, there is increased demand for exam content development, which can be a very labor-intense process. An innovative solution to this challenge has been the use of automatic item generation (AIG) to develop multiple-choice questions (MCQs). In AIG, computer technology is used to generate test items from cognitive models (i.e. representations of the knowledge and skills that are required to solve a problem). The main advantage yielded by AIG is the efficiency in generating items. Although technology for AIG relies on a linear programming approach, the same principles can also be used to improve traditional committee-based processes used in the development of MCQs. Using this approach, content experts deconstruct their clinical reasoning process to develop a cognitive model which, in turn, is used to create MCQs. This approach is appealing because it: (1) is efficient; (2) has been shown to produce items with psychometric properties comparable to those generated using a traditional approach; and (3) can be used to assess higher order skills (i.e. application of knowledge). The purpose of this article is to provide a novel framework for the development of high-quality MCQs using cognitive models. PMID- 26998567 TI - Covalent Bonding of Metal-Organic Framework-5/Graphene Oxide Hybrid Composite to Stainless Steel Fiber for Solid-Phase Microextraction of Triazole Fungicides from Fruit and Vegetable Samples. AB - A hybrid material of the zinc-based metal-organic framework-5 and graphene oxide (metal-organic framework-5/graphene oxide) was prepared as a novel fiber coating material for solid-phase microextraction (SPME). The SPME fibers were fabricated by covalent bonding via chemical cross-linking between the coating material metal organic framework-5/graphene oxide and stainless steel wire. The prepared fiber was used for the extraction of five triazole fungicides from fruit and vegetable samples. Gas chromatography coupled with microelectron capture detector (GC MUECD) was used for quantification. The developed method gave a low limit of detection (0.05-1.58 ng g(-1)) and good linearity (0.17-100 ng g(-1)) for the determination of the triazole fungicides in fruit and vegetable samples. The relative standard deviations (RSDs) for five replicate extractions of the triazole fungicides ranged from 3.7 to 8.9%. The method recoveries for spiked fungicides (5, 20, and 50 ng g(-1)) in grape, apple, cucumber, celery cabbage, pear, cabbage, and tomato samples were in the range of 85.6-105.8% with the RSDs ranging from 3.6 to 11.4%, respectively, depending on both the analytes and samples. The metal-organic framework-5/graphene oxide coated fiber was stable enough for 120 extraction cycles without a significant loss of extraction efficiency. The method was suitable for the determination of triazole fungicides in fruit and vegetable samples. PMID- 26998568 TI - Retrospective diagnosis of two rabies cases in humans by high throughput sequencing. AB - BACKGROUND: Rabies is prevalent in 150 countries and is definitely found in Russian Federation. The average registered incidence of rabies infection among animals in Russia is 3000 cases per year. At least 500,000 cases of animal bites and scratches are registered in the Russia every year, but only 2-4 cases of rabies infection in humans are reported per year. This relatively low incidence of rabies infection among humans is the result of a well-organized program of rabies surveillance and control as well as the readily available vaccination and immunoglobulin therapies. However, physician awareness of rabies infection in patients with acute encephalopathy is low, and some cases of rabies remain undiagnosed. OBJECTIVES: A retrospective study of autopsy materials from patients who died of encephalitis of unknown etiology in the Astrakhan region of Russia in 2003. STUDY DESIGN: A broad-range polymerase chain reaction (PCR) analysis followed by high throughput sequencing were used for the diagnosis. RESULTS: Two cases of rabies were detected and subsequently confirmed using a fluorescent antibody test, an enzyme-linked immunosorbent assay (ELISA) and a mouse inoculation test. Two strains of rabies virus were isolated and characterized using virological methods. The entire genome of each strain was sequenced. PMID- 26998569 TI - International challenge to predict the impact of radioxenon releases from medical isotope production on a comprehensive nuclear test ban treaty sampling station. AB - The International Monitoring System (IMS) is part of the verification regime for the Comprehensive Nuclear-Test-Ban-Treaty Organization (CTBTO). At entry-into force, half of the 80 radionuclide stations will be able to measure concentrations of several radioactive xenon isotopes produced in nuclear explosions, and then the full network may be populated with xenon monitoring afterward. An understanding of natural and man-made radionuclide backgrounds can be used in accordance with the provisions of the treaty (such as event screening criteria in Annex 2 to the Protocol of the Treaty) for the effective implementation of the verification regime. Fission-based production of (99)Mo for medical purposes also generates nuisance radioxenon isotopes that are usually vented to the atmosphere. One of the ways to account for the effect emissions from medical isotope production has on radionuclide samples from the IMS is to use stack monitoring data, if they are available, and atmospheric transport modeling. Recently, individuals from seven nations participated in a challenge exercise that used atmospheric transport modeling to predict the time-history of (133)Xe concentration measurements at the IMS radionuclide station in Germany using stack monitoring data from a medical isotope production facility in Belgium. Participants received only stack monitoring data and used the atmospheric transport model and meteorological data of their choice. Some of the models predicted the highest measured concentrations quite well. A model comparison rank and ensemble analysis suggests that combining multiple models may provide more accurate predicted concentrations than any single model. None of the submissions based only on the stack monitoring data predicted the small measured concentrations very well. Modeling of sources by other nuclear facilities with smaller releases than medical isotope production facilities may be important in understanding how to discriminate those releases from releases from a nuclear explosion. PMID- 26998570 TI - Optimized measurement of radium-226 concentration in liquid samples with radon 222 emanation. AB - Measuring radium-226 concentration in liquid samples using radon-222 emanation remains competitive with techniques such as liquid scintillation, alpha or mass spectrometry. Indeed, we show that high-precision can be obtained without air circulation, using an optimal air to liquid volume ratio and moderate heating. Cost-effective and efficient measurement of radon concentration is achieved by scintillation flasks and sufficiently long counting times for signal and background. More than 400 such measurements were performed, including 39 dilution experiments, a successful blind measurement of six reference test solutions, and more than 110 repeated measurements. Under optimal conditions, uncertainties reach 5% for an activity concentration of 100 mBq L(-1) and 10% for 10 mBq L(-1). While the theoretical detection limit predicted by Monte Carlo simulation is around 3 mBq L(-1), a conservative experimental estimate is rather 5 mBq L(-1), corresponding to 0.14 fg g(-1). The method was applied to 47 natural waters, 51 commercial waters, and 17 wine samples, illustrating that it could be an option for liquids that cannot be easily measured by other methods. Counting of scintillation flasks can be done in remote locations in absence of electricity supply, using a solar panel. Thus, this portable method, which has demonstrated sufficient accuracy for numerous natural liquids, could be useful in geological and environmental problems, with the additional benefit that it can be applied in isolated locations and in circumstances when samples cannot be transported. PMID- 26998572 TI - Long-term stability of core language skill in children with contrasting language skills. AB - This 4-wave longitudinal study evaluated stability of core language skill in 421 European American and African American children, half of whom were identified as low (n = 201) and half of whom were average-to-high (n = 220) in later language skill. Structural equation modeling supported loadings of multivariate age appropriate multisource measures of child language on single latent variables of core language skill at 15 and 25 months and 5 and 11 years. Significant stability coefficients were obtained between language latent variables for children of low and average-to-high language skill, even accounting for child positive social interaction and nonverbal intelligence, maternal education and language, and family home environment. Prospects for children with different language skills and intervention implications are discussed. (PsycINFO Database Record PMID- 26998571 TI - Oxytocin and parent-child interaction in the development of empathy among children at risk for autism. AB - This longitudinal study investigated whether variation in the oxytocin receptor gene (OXTR) and early parent-child interactions predicted later empathic behavior in 84 toddlers at high or low familial risk for autism spectrum disorder. Two well-studied OXTR single-nucleotide polymorphisms, rs53576 and rs2254298, were examined. Parent-child interaction was measured at 15 and 18 months of age during free play sessions. Empathy was measured at 24 and 30 months using a response to parental distress paradigm. While there was no direct association between parent child interaction quality or OXTR and empathy, rs53576 moderated the relation between interaction quality and empathy. Results suggest that the interplay between OXTR and early parent-child interactions predicts individual differences in empathy in children at varying risk for atypical social development. Findings are consonant with a differential susceptibility model in which an OXTR variant may increase the social salience of interaction processes for specific allele carriers. These results increase our understanding of predictors of empathy development in young children with a wide range of social outcomes. (PsycINFO Database Record PMID- 26998574 TI - Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Review and Neuropsychological Case Study. AB - OBJECTIVE: Anti-N-Methyl-d-Aspartate Receptor (NMDAR) Encephalitis is an autoimmune-mediated encephalitis, which may be associated with a tumor, which occurs when antibodies bind central NMDA receptors. Although typically diagnosed in women, approximately 20% of cases have been males. Due to the challenges with identification, imaging, and diverse symptom presentation, this syndrome is often misdiagnosed. Accurate diagnosis may provide an opportunity for introduction of disease-modifying therapies, which may alter disease trajectory. Moreover, neuropsychology has yet to fully clarify the pattern of impairments expected with this disorder. METHODS: This manuscript reviews a single case study of a 42-year old male diagnosed with NMDAR encephalitis. Neuropsychological evaluation was completed subsequent to diagnosis, treatment, and rehabilitation. Ongoing patient complaints, approximately six months post diagnosis, included reduced sustained attention, poor word retrieval, and daily forgetfulness. Adaptive skills were improved following rehabilitation. RESULTS: Direct testing revealed mildly impaired sustained attention, processing speed, oral word fluency, and executive functioning. All other cognitive domains were within estimated premorbid range, low average to average. CONCLUSIONS: Neuropsychological deficits were consistent with mild frontal brain dysfunction and continued recovery. This case illustrates the need for medical and psychological practitioners to understand NMDAR encephalitis, its symptom presentation, and related neuropsychological impact; particularly with the potential for misdiagnosis. PMID- 26998575 TI - Biosensor-based engineering of biosynthetic pathways. AB - Biosynthetic pathways provide an enzymatic route from inexpensive renewable resources to valuable metabolic products such as pharmaceuticals and plastics. Designing these pathways is challenging due to the complexities of biology. Advances in the design and construction of genetic variants has enabled billions of cells, each possessing a slightly different metabolic design, to be rapidly generated. However, our ability to measure the quality of these designs lags by several orders of magnitude. Recent research has enabled cells to report their own success in chemical production through the use of genetically encoded biosensors. A new engineering discipline is emerging around the creation and application of biosensors. Biosensors, implemented in selections and screens to identify productive cells, are paving the way for a new era of biotechnological progress. PMID- 26998577 TI - Development and Validation of a Simplified Falls Assessment Tool in an Acute Care Setting. AB - An easy-to-use assessment tool, which contains reversible risk factors, might influence the success of a falls prevention program. A 2-phase study was undertaken to develop and validate a simplified falls assessment tool. Risk factors of confusion, dizziness, altered elimination, and difficulty with mobility were found to be significantly associated with fall status. The simplified falls assessment tool that contains these 4 risk factors yielded a comparable predictive value to Hendrich II Falls Risk Model. PMID- 26998576 TI - Utilization of healthcare services among elderly with cognitive impairment no dementia and influence of depression and anxiety: a longitudinal study. AB - OBJECTIVES: Little objective and nationally representative data are available concerning the influence of cognitive impairment no dementia (CIND) on utilization of healthcare services. The main objective was to compare the use of healthcare services over three years, between elders with current or incident CIND and those without CIND. A second objective was to evaluate the effect of depression and anxiety. METHODS: Cross-sectional and longitudinal data from a population-based survey of 2265 older adults living in Quebec (Canada) were used. CIND was identified using normative data for the Mini-Mental State Examination and was linked with medical records from public health insurance plan. Multinomial logistic regressions adjusted for relevant socio-demographic, social network and health-related confounders were conducted for each service. Interaction between CIND and depression/anxiety was also examined. MAIN RESULTS: Current CIND was a predictor of longer anxiolytic/sedative/hypnotic medication use. Incident CIND led to longer hospital stay. Depression raised the likelihood of frequenting geriatricians, psychiatrists or neurologists and emergency department, but lessened the likelihood of visiting general practitioners. The addition of the psychiatric conditions to the incident CIND did not increase the likelihood of consuming antidepressants, while the incident CIND cases without psychiatric conditions increased this likelihood. DISCUSSION: Compared to older adults without CIND, older adults with CIND have a distinct utilization of healthcare services. Multiple evaluations over many years may help to better understand the utilization of healthcare services in individuals with CIND. In the meantime, evaluations of these conditions at key moments could allow a more efficient use of health resources. PMID- 26998578 TI - A Measure of Lean Quality Improvement for Hospital Staff Nurses. AB - In this study, a measure of Lean management was developed and tested. Items were identified using the Delphi technique with literature review and expert responses. Twenty-five nurses pilot-tested the instrument and then 212 nurses in 5 hospitals completed the instrument, and their responses were subjected to exploratory factor analysis. The 75-item instrument includes 12 factors describing Lean management conceptualization. Reliability and validity are acceptable for a new instrument. PMID- 26998579 TI - Some thoughts on health surveillance data, race, and population categorization. PMID- 26998580 TI - Skin mast cells: are we missing the forest for the trees? PMID- 26998582 TI - Automated background subtraction technique for electron energy-loss spectroscopy and application to semiconductor heterostructures. AB - Electron energy-loss spectroscopy (EELS) has become a standard tool for identification and sometimes also quantification of elements in materials science. This is important for understanding the chemical and/or structural composition of processed materials. In EELS, the background is often modelled using an inverse power-law function. Core-loss ionization edges are superimposed on top of the dominating background, making it difficult to quantify their intensities. The inverse power-law has to be modelled for each pre-edge region of the ionization edges in the spectrum individually rather than for the entire spectrum. To achieve this, the prerequisite is that one knows all core losses possibly present. The aim of this study is to automatically detect core-loss edges, model the background and extract quantitative elemental maps and profiles of EELS, based on several EELS spectrum images (EELS SI) without any prior knowledge of the material. The algorithm provides elemental maps and concentration profiles by making smart decisions in selecting pre-edge regions and integration ranges. The results of the quantification for a semiconductor thin film heterostructure show high chemical sensitivity, reasonable group III/V intensity ratios but also quantification issues when narrow integration windows are used without deconvolution. PMID- 26998581 TI - Analysis of Patterns of Physical Activity and Sedentary Behavior in an Urban Slum Setting in Nairobi, Kenya. AB - BACKGROUND: Insufficient physical activity and sedentary behavior are key risk factors for the emergence of noncommunicable diseases in the sub-Saharan African setting. Given the limited evidence base, research is required to understand the trends. OBJECTIVES: This study describes the patterns of physical activity and sedentary behavior in a large sample of urban slum residents in Nairobi, Kenya. METHODS: We used data collected from 5190 study participants as part of cardiovascular disease risk assessment. Data were collected about work-, transport-, and recreation-related physical activity as well as sitting and sleeping time. Using time spent on each type of physical activity and respective metabolic equivalents (METs), patterns of physical activity and associated factors were evaluated using descriptive statistics, Pearson correlations, and logistic regression. RESULTS: Nearly 50% of the study population was involved in work-related physical activities, whereas only 6.3% was involved in recreation related physical activities. Involvement in physical activities decreased with age, and 17.4% had <600 MET-minutes per week. Higher sitting time was associated with insufficient physical activity. There were substantial gender differences in the time spent for physical activity. CONCLUSIONS: Given the positive relationship between insufficient physical activity and sedentary behavior, complementary interventions that improve physical activity and at the same time reduce sitting time are needed. PMID- 26998583 TI - Antithrombin for the prevention of intraventricular hemorrhage in very preterm infants. AB - BACKGROUND: Preterm birth remains the major risk factor for the development of intraventricular hemorrhage, an injury that occurs in 25% of very low birth weight infants. Intraventricular hemorrhage is thought to be venous in origin and intrinsic thromboses in the germinal matrix are likely to play a triggering role. Antithrombin, a glycoprotein synthesized in the liver, is the major plasma inhibitor of thrombin thus modulating blood coagulation. Very low birth weight newborn infants have low levels of antithrombin and the risk of developing intraventricular hemorrhage is increased by the presence of hypercoagulability in the first hours of life. The administration of anticoagulants such as antithrombin may offset the increased risk of developing intraventricular hemorrhage. Anticoagulants may also reduce the risk of developing parenchymal venous infarct, a condition known to complicate intraventricular hemorrhage. OBJECTIVES: To assess whether the prophylactic administration of antithrombin (started within the first 24 hours after birth) reduces the incidence of germinal matrix-intraventricular hemorrhage in very preterm neonates when compared to placebo, no treatment, or heparin. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2015), MEDLINE (1996 to 22 November 2015), EMBASE (1980 to 22 November 2015), and CINAHL (1982 to 22 November 2015). No language restrictions were applied. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia and New Zealand and Pediatric Academic Societies) from 2000 to 2015. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials and cluster trials comparing the administration of early, i.e. within the first 24 hours of life, antithrombin in very preterm infants (gestational age < 32 weeks, any birth weight). DATA COLLECTION AND ANALYSIS: For each of the included trials, two authors independently extracted data (e.g. number of participants, birth weight, gestational age, antithrombin formulation (plasma-derived or recombinant), mode of administration, and duration of therapy, etc.) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review are intraventricular hemorrhage and severe intraventricular hemorrhage. MAIN RESULTS: Two randomized controlled trials, for a total of 182 infants, met the inclusion criteria of this review. Both trials compared antithrombin with placebo. We found no significant differences in the rates of intraventricular hemorrhage (typical RR 1.30, CI 95% 0.87 to 1.93, typical RD 0.09, 95% CI -0.05 to 0.23; 2 studies, 175 infants; I2 = 18% for RR and I2 = 42% for RD) and severe intraventricular hemorrhage (typical RR 1.04, CI 95% 0.55 to 1.94; typical RD 0.01, 95% CI -0.11 to 0.12; 2 studies, 175 infants; I2 = 0% for RR and I2 = 0% for RD). Among secondary outcomes, we found no significant differences in terms of neonatal mortality (typical RR 2.00, CI 95% 0.62 to 6.45; typical RD 0.04, 95% CI -0.03 to 0.12; 2 studies, 182 infants; I2 = 46% for RR and I2 = 61% for RD) and in the other specified outcomes, such as bronchopulmonary dysplasia. The quality of the evidence supporting these findings is limited due to the imprecision of the estimates. AUTHORS' CONCLUSIONS: The administration of antithrombin seems not to reduce the incidence and severity of intraventricular hemorrhage in very preterm infants. Limited evidence is available on other clinically relevant outcomes. Given the imprecision of the estimate, the results of this systematic review are consistent with either a benefit or a detrimental effect of antithrombin and do not provide a definitive answer to the review question. PMID- 26998584 TI - Parkinson Disease Risk in Patients With Rosacea. PMID- 26998585 TI - Hypermethylated DNA as a biomarker for colorectal cancer: a systematic review. AB - AIM: Improved methods for early detection of colorectal cancer (CRC) are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. Biochemical methods have improved in recent years, and several hypermethylated genes that are sensitive and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed. METHOD: A systematic literature search was performed using the Medline, Web of Science and Embase databases. Studies were included if they analysed hypermethylated genes from stool or blood samples in correlation with CRC. Studies in languages other than English and those based on animal models or cell lines were excluded. RESULTS: The literature search yielded 74 articles, including 43 addressing blood samples and 31 addressing stool samples. In blood samples, hypermethylated ALX4, FBN2, HLTF, P16, TMEFF1 and VIM were associated with poor prognosis, hypermethylated APC, NEUROG1, RASSF1A, RASSF2A, SDC2, SEPT9, TAC1 and THBD were detected in early stage CRC and hypermethylated P16 and TFPI2 were associated with CRC recurrence. In stool samples, hypermethylated BMP3, PHACTR3, SFRP2, SPG20, TFPI2 and TMEFF2 were associated with early stage CRC. CONCLUSION: Hypermethylation of the promoters of specific genes measured in blood or stool samples could be used as a CRC biomarker and provide prognostic information. The majority of studies, however, include only a few patients with poorly defined control groups. Further studies are therefore needed before hypermethylated DNA can be widely applied as a clinical biomarker for CRC detection and prognosis. PMID- 26998586 TI - A General Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Aryl and Heteroaryl Chlorides. AB - A general palladium-catalyzed Hiyama cross-coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)2 /L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/L2 system and the water addition protocol can efficiently catalyze a broad range of electron rich, -neutral, -deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis. PMID- 26998588 TI - Erratum: phiXANES: In vivo imaging of metal-protein coordination environments. PMID- 26998587 TI - Exercise and Repeated Testing Improves Accuracy of Laser Doppler Assessment of Microvascular Function Following Shortened (1-minute) Blood Flow Occlusion. AB - OBJECTIVES: To determine whether stability/accuracy of post-occlusive LDF following shortened, one-minute blood flow occlusion, increases in the post exercise state or by averaging multiple measurements. METHODS: Six healthy adults (3F) underwent LDF eight times at rest and following exercise, assessing post occlusive (one-minute occlusion) reactive hyperemia in the cutaneous microcirculation of the forefinger. Measured variables included: pre- and post occlusion steady-state perfusion (Plat1, Plat2), maximum post-occlusive perfusion (Max), PkT, and the ratio Max/Plat1. RESULTS: Stability/accuracy of all variables improved performing measurements after exercise (p < 0.05 Plat 1, Plat 2, Max and Max/Plat1). PkT and Max/Plat 1 displayed the greatest accuracy at rest (26.6 +/- 5.1% and 26.6 +/- 4.4% average difference, %Diff, of single measurements from individual "true" means, respectively); for these variables, %Diff improved to 19.5 +/- 5.3 and 17.6 +/- 2.1, respectively, following exercise. Overall, averaging multiple measurements performed at rest also improved stability/accuracy in all variables. This improvement was comparable to that obtained with a single measurement following exercise. CONCLUSIONS: A standardized exercise stimulus prior to testing significantly improves stability/accuracy of LDF following shortened, one-minute blood flow occlusion. Our results suggest the possibilities of broader applications of exercise to optimize measurements from a variety of skin perfusion methodologies. PMID- 26998589 TI - Is specialization an evolutionary dead end? Testing for differences in speciation, extinction and trait transition rates across diverse phylogenies of specialists and generalists. AB - Specialization has often been claimed to be an evolutionary dead end, with specialist lineages having a reduced capacity to persist or diversify. In a phylogenetic comparative framework, an evolutionary dead end may be detectable from the phylogenetic distribution of specialists, if specialists rarely give rise to large, diverse clades. Previous phylogenetic studies of the influence of specialization on macroevolutionary processes have demonstrated a range of patterns, including examples where specialists have both higher and lower diversification rates than generalists, as well as examples where the rates of evolutionary transitions from generalists to specialists are higher, lower or equal to transitions from specialists to generalists. Here, we wish to ask whether these varied answers are due to the differences in macroevolutionary processes in different clades, or partly due to differences in methodology. We analysed ten phylogenies containing multiple independent origins of specialization and quantified the phylogenetic distribution of specialists by applying a common set of metrics to all datasets. We compared the tip branch lengths of specialists to generalists, the size of specialist clades arising from each evolutionary origin of a specialized trait and whether specialists tend to be clustered or scattered on phylogenies. For each of these measures, we compared the observed values to expectations under null models of trait evolution and expected outcomes under alternative macroevolutionary scenarios. We found that specialization is sometimes an evolutionary dead end: in two of the ten case studies (pollinator-specific plants and host-specific flies), specialization is associated with a reduced rate of diversification or trait persistence. However, in the majority of studies, we could not distinguish the observed phylogenetic distribution of specialists from null models in which specialization has no effect on diversification or trait persistence. PMID- 26998590 TI - The German Hypertension League (Deutsche Hochdruckliga) Quality Seal Protocol for blood pressure-measuring devices: 15-year experience and results from 105 devices for home blood pressure control. AB - OBJECTIVE: The German Hypertension League (Deutsche Hochdruckliga) established a program to assess the accuracy and reliability of blood pressure (BP)-measuring devices in 1999 (Quality Seal Protocol). Here, we report on the results of a testing series of 105 devices designed for BP self-measurement. METHODS: The test protocol for the validation of upper-arm, wrist, and finger devices was developed to compare device to conventional Riva-Rocci measurements based on five criteria: mean systolic and mean diastolic differences, their standard deviations, and a point score representing the correlation of systolic and diastolic errors of individual comparisons. The results of this testing are summarized. RESULTS: From 1999 to 2014, a total of 105 BP devices for self-measurement were tested according to the Quality Seal Protocol. Of these, 47.6% fulfilled all five validation criteria, 55.7% of the upper-arm devices (39 of 71) and 32.4% (11 of 34) of the wrist devices. Finger devices were not offered for testing. Forty-four devices (41.9%) failed multiple test criteria of the validation procedure. A subanalysis with 51 devices tested showed that a stricter definition of the passing point score with a limit of at least 55% would slightly increase the consistency with the conventional criteria in comparison with a point score criterion of at least 50%. It was therefore introduced in 2007. CONCLUSION: The results indicate the importance of a rigorous testing of a BP-measuring device used for home BP measurement to prevent patients from making erroneous treatment decisions. PMID- 26998591 TI - Ergonomics in dentistry: experiences of the practice by dental students. AB - OBJECTIVE: The aim of this study was to qualitatively evaluate the experiences of students enrolled in the last year of dentistry school with ergonomic practice. METHODS: This is a qualitative, observational and cross-sectional study, with a non-probabilistic sample design. The sample comprised students enrolled in the last year of dentistry in Araraquara-UNESP (n = 29). The data were collected by means of open semi-structured and individual interviews, captured by a digital voice recorder. The students were interviewed in their own university at a time that was previously scheduled, and care was taken to provide a private and welcoming environment to carry out the interviews. A script containing questions related to practices in ergonomics was prepared at the university. Data analysis was carried out using the qualitative-quantitative Collective Subject Discourse technique with the aid of Qualiquantisoft(r) software program. RESULTS: It was found that more than half of the students (58.6%) believe that adopting an ergonomic posture is important to prevent future problems, pain and occupational diseases, and 62.1% of the students confirm having difficulties in adopting ergonomic postures due to the types of treatment required and the regions of the mouth being treated. The main reasons stated for the fact that their colleagues do not adopt ergonomic postures are lack of attention, practice and forgetfulness (44.8%) and difficulty in visualising the operatory field or the procedure performed (27.6%). CONCLUSION: It is possible to conclude that the students interviewed know ergonomic principles and their importance in occupational health. However, they found it difficult to put these principles into practice. PMID- 26998592 TI - Classifying neonatal growth outcomes: use of birth weight, placental evaluation and individualized growth assessment. AB - OBJECTIVE: To compare neonatal growth outcomes determined by birth weight (BW), placental assessment (Plac Assess) and individualized growth assessment (IGA). METHODS: This retrospective analysis was carried out in 45 selected pregnancies at risk for fetal growth restriction. Serial fetal biometry was carried out in the 2nd and 3rd trimester. First and second trimester placental biomarkers, 2nd trimester uterine artery (Ut A) velocimetry and postnatal placental pathology were evaluated as indicators of placental insufficiency. At delivery, weight (WT), head circumference (HC) and crown-heel length (CHL) were measured. BWs were categorized as large-for-gestational-age (LGA), appropriate-for-gestational-age (AGA) and small-for-gestational age (SGA) (<10th, 10th-90th and >90th percentiles). In these categories, neonatal growth outcomes were classified as growth restricted (GR), normal (NORMAL) or macrosomic (MACRO) based on BW plus Plac Assess (Ut A velocimetry, biomarkers, pathology) or IGA [growth potential realization index profile (WT, HC and CHL)]. RESULTS: There were 6 LGA, 14 AGA and 25 SGA neonates in this sample. All 14 AGA neonates were considered NORMAL by both IGA and BW + Plac Assess. All six LGA neonates were classified as MACRO by BW + Plac Assess but only four by IGA (the remaining two were NORMAL and high NORMAL). The 25 SGA cases could be divided into five subgroups based on IGA and BW + Plac Assess. The largest subgroup (56%) was GR and the next largest (24%) was NORMAL by both classification methods. In the remaining 20%, there was some evidence of GR but IGA and BW + Plac Assess were not in complete agreement. CONCLUSIONS: Agreement was good for all three methods in the LGA and AGA groups. The SGA group was heterogeneous but agreement between IGA and BW + Plac Assess was 89%. These results, using more sophisticated growth assessment methods, confirm placental insufficiency as a primary cause of growth restriction. Most normal and GR SGA neonates can be identified with conventional anatomical measurements if IGA is used. PMID- 26998594 TI - Bereaved Caregiver Perspectives on the End-of-Life Experience of Patients With a Left Ventricular Assist Device. AB - IMPORTANCE: For patients and their loved ones, decisions regarding the end of life in the setting of chronic progressive illness are among the most complex in health care. Complicating these decisions are increasingly available, invasive, and potentially life-prolonging technologies such as the left ventricular assist device (LVAD). OBJECTIVE: To understand the experience of bereaved caregivers and patients at the end of life who have an LVAD. DESIGN, SETTING, AND PARTICIPANTS: Semistructured, in-depth interviews were conducted between September 10 and November 21, 2014, with 8 bereaved caregivers of patients with an LVAD who were recruited from a single institution. Data were analyzed from December 13, 2014, to February 18, 2015, using a mixed inductive and deductive approach. MAIN OUTCOMES AND MEASURES: Themes from semistructured interviews. RESULTS: The 8 caregivers (6 females) described 3 main themes that coalesced around feelings of confusion in the final weeks with their loved ones: (1) the process of death with an LVAD, (2) the legal and ethically permissible care of patients with an LVAD approaching death, and (3) fragmented integration of palliative and hospice care. CONCLUSIONS AND RELEVANCE: Despite increasing use of LVADs in patients with advanced heart failure, bereaved caregivers of patients with an LVAD describe a high level of confusion at the end of life. There remains a need for the health care community to develop clear guidance on the management of patients with an LVAD at the end of life. Future work will focus on the educational process and the ideal timing and reiteration of such information to patients and families. PMID- 26998593 TI - Motorcycle helmet use and the risk of head, neck, and fatal injury: Revisiting the Hurt Study. AB - Most studies find strong evidence that motorcycle helmets protect against injury, but a small number of controversial studies have reported a positive association between helmet use and neck injury. The most commonly cited paper is that of Goldstein (1986). Goldstein obtained and reanalyzed data from the Hurt Study, a prospective, on-scene investigation of 900 motorcycle collisions in the city of Los Angeles. The Goldstein results have been adopted by the anti-helmet community to justify resistance to compulsory motorcycle helmet use on the grounds that helmets may cause neck injuries due to their mass. In the current study, we replicated Goldstein's models to understand how he obtained his unexpected results, and we then applied modern statistical methods to estimate the association of motorcycle helmet use with head injury, fatal injury, and neck injury among collision-involved motorcyclists. We found Goldstein's analysis to be critically flawed due to improper data imputation, modeling of extremely sparse data, and misinterpretation of model coefficients. Our new analysis showed that motorcycle helmets were associated with markedly lower risk of head injury (RR 0.40, 95% CI 0.31-0.52) and fatal injury (RR 0.44, 95% CI 0.26-0.74) and with moderately lower but statistically significant risk of neck injury (RR 0.63, 95% CI 0.40-0.99), after controlling for multiple potential confounders. PMID- 26998595 TI - Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review. AB - Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs' mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5-36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and 'high-dose' glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine-related consequences of this novel class of immunotherapies. PMID- 26998596 TI - Screening and characterizing a denitrifying phosphorus-accumulating bacterium isolated from a circular plug-flow reactor. AB - Denitrifying phosphorus-accumulating organisms (DNPAO) are viewed as one of the most effective means to solve the removal contradiction of nitrogen and phosphorus in wastewater treatment. In this study, we isolated a DNPAO (C-17, accession number: KU745702) from activated sludge in a patented circular plug flow reactor, physiologically to Pseudomonas sp. based on 16S rRNA sequence and phenotypic characteristics. The results of denitrifying phosphorus-accumulating experiment showed that Pseudomonas C-17 has high removal efficiencies for [Formula: see text] and NO3-N, 75% and 87%, respectively. The ratio of phosphorus release was 25.0 mg [Formula: see text] (with anabolism) and 26.8 mg [Formula: see text] (without anabolism), respectively. Our results indicated that Pseudomonas C-17 had strong capacity of phosphorus release, and its uptake is often imprecisely evaluated by ignoring the part of metabolic consumption. Pseudomonas C-17 is capable of utilizing oxygen, nitrate and nitrite as electron acceptors under experimental conditions. PMID- 26998597 TI - Autosomal dominant spinal muscular atrophy with lower extremity predominance: A recognizable phenotype of BICD2 mutations. AB - INTRODUCTION: Heterozygous BICD2 gene mutations cause a form of autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED). METHODS: We analyzed the BICD2 gene in a selected group of 25 index patients with neurogenic muscle atrophy. RESULTS: We identified 2 new BICD2 missense mutations, c.2515G>A, p.Gly839Arg, in a family with autosomal dominant inheritance, and c.2202G>T, p.Lys734Asn, as a de novo mutation in an isolated patient with similar phenotype. The patients had congenital foot contractures, muscle atrophy of the legs, and slowly progressive weakness of the shoulder girdle. There was no apparent sensory or brain dysfunction. One patient died of unrelated reasons at age 52 years. Autopsy revealed no upper motor neuron and only moderate lower motor neuron loss, but there was distal corticospinal tract degeneration and marked neurogenic muscular atrophy. CONCLUSION: These findings give further insight into the clinical and pathoanatomical consequences of BICD2 mutations. Muscle Nerve 54: 496-500, 2016. PMID- 26998598 TI - Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival. AB - Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage-associated molecular pattern protein high mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia-inducible factor 1alpha and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant. PMID- 26998599 TI - Patient characteristics for different therapeutic strategies in the management ketamine cystitis. AB - AIMS: Long-term ketamine abuse results in severely inflamed bladder and intractable bladder pain. Currently there is no guideline for clinician to follow how to manage patients with ketamine cystitis (KC). This study analyzed the KC patient characteristics between who received conservative management and augmentation enterocystoplasty (AE). METHODS: A total of 53 patients with chronic ketamine abuse and lower urinary tract symptoms were included in this study. All of the patients have been initially treated conservatively but fail. They were admitted for detailed urological examinations. Patients were classified according to their maximal bladder capacity (MBC). The patients with extremely small MBC (<100 ml) with or without upper urinary tract damage and very small MBC with upper urinary tract damage were recommended to receive AE. The patient characteristics and treatment outcome are compared between patients with AE and conservative treatment. RESULTS: Among them, 28 patients underwent AE and 25 were managed with conservative treatment. The only significant difference between groups was more patients with urgency urinary incontinence underwent AE. Patients underwent AE had significantly smaller MBC, thicker bladder wall, and higher incidence of vesicoureteral reflux. Patients underwent AE reported a good outcome. Most of patients received conservative treatment had a fair result. CONCLUSIONS: KC patients who already developed a contracted bladder with extremely small bladder capacity (<300 ml) with irreversible urinary tract change, partial cystectomy, and AE seems necessary for early restoration of a normal lower urinary tract function. The treatment outcome of AE is better than patients with conservative treatment. Neurourol. Urodynam. 36:687-691, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26998600 TI - Schizophrenia genetics complements its mechanistic understanding. PMID- 26998602 TI - On dealing with the pollution costs in agriculture: A case study of paddy fields. AB - The main purpose of this study is to evaluate marginal abatement cost of the main agricultural pollutants. In this sense, we construct three indices including Net Global Warming Potential (NGWP) and Nitrogen Surplus (NS), simulated by a biogeochemistry model, and also an Environmental Impact Quotient (EQI) for paddy fields. Then, using a Data Envelopment Analysis (DEA) model, we evaluate environmental inefficiencies and shadow values of these indices. The results show that there is still room for improvement at no extra cost just through a better input management. Besides, enormous potential for pollution reduction in the region is feasible. Moreover, in paddy cultivation, marginal abatement cost of pesticides and herbicides are much bigger than nitrogen surplus and greenhouse gasses. In addition, in the status quo, the mitigation costs are irrelevant to production decisions. Finally, to deal with the private pollution costs, market based instruments are proved to be better than command-and-control regulation. PMID- 26998603 TI - The Quality of Rare Disease Registries: Evaluation and Characterization. AB - BACKGROUND: The focus on the quality of the procedures for data collection, storing, and analysis in the definition and implementation of a rare disease registry (RDR) is the basis for developing a valid and long-term sustainable tool. The aim of this study was to provide useful information for characterizing a quality profile for RDRs using an analytical approach applied to RDRs participating in the European Platform for Rare Disease Registries 2011-2014 (EPIRARE) survey. METHODS: An indicator of quality was defined by choosing a small set of quality-related variables derived from the survey. The random forest method was used to identify the variables best defining a quality profile for RDRs. Fisher's exact test was employed to assess the association with the indicator of quality, and the Cochran-Armitage test was used to check the presence of a linear trend along different levels of quality. RESULTS: The set of variables found to characterize high-quality RDRs focused on ethical and legal issues, governance, communication of activities and results, established procedures to regulate access to data and security, and established plans to ensure long-term sustainability. CONCLUSIONS: The quality of RDRs is usually associated with a good oversight and governance mechanism and with durable funding. The results suggest that RDRs would benefit from support in management, information technology, epidemiology, and statistics. PMID- 26998604 TI - Ancient DNA from 8400 Year-Old Catalhoyuk Wheat: Implications for the Origin of Neolithic Agriculture. AB - Human history was transformed with the advent of agriculture in the Fertile Crescent with wheat as one of the founding crops. Although the Fertile Crescent is renowned as the center of wheat domestication, archaeological studies have shown the crucial involvement of Catalhoyuk in this process. This site first gained attention during the 1961-65 excavations due to the recovery of primitive hexaploid wheat. However, despite the seeds being well preserved, a detailed archaeobotanical description of the samples is missing. In this article, we report on the DNA isolation, amplification and sequencing of ancient DNA of charred wheat grains from Catalhoyuk and other Turkish archaeological sites and the comparison of these wheat grains with contemporary wheat species including T. monococcum, T. dicoccum, T. dicoccoides, T. durum and T. aestivum at HMW glutenin protein loci. These ancient samples represent the oldest wheat sample sequenced to date and the first ancient wheat sample from the Middle East. Remarkably, the sequence analysis of the short DNA fragments preserved in seeds that are approximately 8400 years old showed that the Catalhoyuk wheat stock contained hexaploid wheat, which is similar to contemporary hexaploid wheat species including both naked (T. aestivum) and hulled (T. spelta) wheat. This suggests an early transitory state of hexaploid wheat agriculture from the Fertile Crescent towards Europe spanning present-day Turkey. PMID- 26998605 TI - Continuous Venovenous Hemodiafiltration in the Treatment of Maple Syrup Urine Disease. AB - BACKGROUND: The study aims to define the efficacy of continuous renal replacement therapy in acute metabolic decompensation treatment of maple syrup urine disease (MSUD). METHODS: All the neonates, infants and children who have had life threatening conditions due to MSUD and were treated with continuous venovenous hemodiafiltration (CVVHDF) were analyzed retrospectively. RESULTS: Fourteen patients underwent 15 sessions of CVVHDF (age range 15 days to 87 months, mean 40.8 +/- 31.4 months). One patient required additional CVVHDF 1 week after cessation of CVVHDF. Twenty seven percent (n = 4) of the patients were intubated and mechanically ventilated. Twelve patients responded to treatment and dramatic neurological improvement was observed within 24 h. Two of the 14 patients required 36 h of CVVHDF for neurological improvement. The mean duration of CVVHDF was 20.2 +/- 8.6 (9-36) h. The mean leucine level was 1,648 +/- 623.8 (714-2,768) MUmol/l before and was 256.5 +/- 150.6 (117-646) MUmol/l at the end of treatment. No mortality was observed. CONCLUSION: Continuous hemodiafiltration is an effective and safe method in correcting metabolic disturbances in MSUD. PMID- 26998601 TI - C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. AB - Neuronal inclusions of poly(GA), a protein unconventionally translated from G4C2 repeat expansions in C9ORF72, are abundant in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) caused by this mutation. To investigate poly(GA) toxicity, we generated mice that exhibit poly(GA) pathology, neurodegeneration and behavioral abnormalities reminiscent of FTD and ALS. These phenotypes occurred in the absence of TDP-43 pathology and required poly(GA) aggregation. HR23 proteins involved in proteasomal degradation and proteins involved in nucleocytoplasmic transport were sequestered by poly(GA) in these mice. HR23A and HR23B similarly colocalized to poly(GA) inclusions in C9ORF72 expansion carriers. Sequestration was accompanied by an accumulation of ubiquitinated proteins and decreased xeroderma pigmentosum C (XPC) levels in mice, indicative of HR23A and HR23B dysfunction. Restoring HR23B levels attenuated poly(GA) aggregation and rescued poly(GA)-induced toxicity in neuronal cultures. These data demonstrate that sequestration and impairment of nuclear HR23 and nucleocytoplasmic transport proteins is an outcome of, and a contributor to, poly(GA) pathology. PMID- 26998607 TI - Rituximab Effectiveness and Safety for Treating Primary Sjogren's Syndrome (pSS): Systematic Review and Meta-Analysis. AB - BACKGROUND: Primary Sjogren's Syndrome (pSS) is a systemic autoimmune disease that involves the exocrine glands and internal organs. pSS leads to destruction and loss of secretory function due to intense lymphoplasmacytic infiltration. Therapeutic options include mainly symptomatic and supportive measures, and traditional immunosuppressant drugs have shown no effectiveness in randomized trials. Rituximab (RTX) is a chimeric antibody anti-CD20 that leads to B cell depletion by diverse mechanisms. There is evidence that this drug may be effective for treating pSS. The objective of this systematic review was to evaluate Rituximab effectiveness and safety for treating pSS. METHODS AND FINDINGS: We conducted a systematic review of RCTs published until December 2015, with no language restriction. We registered a protocol on Plataforma Brasil (40654814.6.0000.5505) and developed search strategies for the following scientific databases: MEDLINE, EMBASE, CENTRAL and LILACS. We included adults with established pSS diagnosis and considered the use of Rituximab as intervention and the use of other drugs or placebo as control. Four studies met our eligibility criteria: three with low risk of bias and one with uncertain risk of bias. The total number of participants was 276 (145 RTX, 131 placebo). We assessed the risk of bias of each included study and evaluated the following as primary outcomes: lacrimal gland function, salivary gland function, fatigue improvement and adverse events. We found no significant differences between the groups in the Schirmer test at week 24 meta-analysis (MD 3.59, 95% CI -2.89 to 10.07). Only one study evaluated the lissamine green test and reported a statistically significant difference between the groups at week 24 (MD -2.00, 95% CI -3.52 to -0.48). There was a significant difference between the groups regarding salivary flow rate (MD 0.09, 95% CI 0.02 to 0.16) and improvement in fatigue VAS at weeks 6 (RR 3.98, 95% CI 1.61 to 9.82) and week 16 (RR 3.08, 95% CI 1.21 to 7.80). CONCLUSIONS: According to moderate quality evidence, the treatment with a single RTX course in patients with SSp presents discrete effect for improving lacrimal gland function. Low-quality evidence indicates the potential of this drug for improving salivary flow. According to low quality evidence, no differences were observed in the evaluation after 24 weeks regarding fatigue reduction (30% VAS), serious adverse events occurrence, quality of life improvement and disease activity. With a very low level of evidence, there was no improvement in oral dryness VAS evaluation. PMID- 26998606 TI - Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution. AB - Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis). Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies. PMID- 26998608 TI - Barefoot Plantar Pressure Indicates Progressive Neurological Damage in Patients with Human T-Cell Lymphotropic Virus Type 1 Infection. AB - BACKGROUND: The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals. METHODOLOGY: We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient's clinical history and examinations of the patient's reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed. MAIN FINDINGS: The prevalence of neurological disturbances-altered reflexes and skin tactile sensitivity and increased risk of falling-was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV 1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects. CONCLUSIONS: The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection. PMID- 26998609 TI - Antimicrobial Combinations against Pan-Resistant Acinetobacter baumannii Isolates with Different Resistance Mechanisms. AB - The study investigated the effect of antibiotic combinations against 20 clinical isolates of A. baumannii (seven colistin-resistant and 13 colistin-susceptible) with different resistance mechanisms. Clinical data, treatment, and patient mortality were evaluated. The following methods were used: MIC, PCRs, and outer membrane protein (OMP) analysis. Synergy was investigated using the checkerboard and time-kill methods. Clonality was evaluated by PFGE. Based on clonality, the whole genome sequence of six A. baumannii isolates was analyzed. All isolates were resistant to meropenem, rifampicin, and fosfomycin. OXA-23 and OXA-143 were the most frequent carbapenemases found. Four isolates showed loss of a 43kDa OMP. The colistin-susceptible isolates belonged to different clones and showed the highest synergistic effect with fosfomycin-amikacin. Among colistin-resistant isolates, the highest synergistic effect was observed with the combinations of colistin-rifampicin followed by colistin-vancomycin. All colistin-resistant isolates harbored blaOXA-23-like and belonged to CC113. Clinical and demographic data were available for 18 of 20 patients. Fourteen received treatment and eight patients died during treatment. The most frequent site of infection was the blood in 13 of 14 patients. Seven patients received vancomycin plus an active drug against A. baumannii; however, mortality did not differ in this group. The synergistic effect was similar for colistin-susceptible isolates of distinct clonal origin presenting with the same resistance mechanism. Overall mortality and death during treatment was high, and despite the high synergism in vitro with vancomycin, death did not differ comparing the use or not of vancomycin plus an active drug against A. baumannii. PMID- 26998611 TI - Differential Item Functioning in the SF-36 Physical Functioning and Mental Health Sub-Scales: A Population-Based Investigation in the Canadian Multicentre Osteoporosis Study. AB - BACKGROUND: Self-reported health status measures, like the Short Form 36-item Health Survey (SF-36), can provide rich information about the overall health of a population and its components, such as physical, mental, and social health. However, differential item functioning (DIF), which arises when population sub groups with the same underlying (i.e., latent) level of health have different measured item response probabilities, may compromise the comparability of these measures. The purpose of this study was to test for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scale items in a Canadian population based sample. METHODS: Study data were from the prospective Canadian Multicentre Osteoporosis Study (CaMos), which collected baseline data in 1996-1997. DIF was tested using a multiple indicators multiple causes (MIMIC) method. Confirmatory factor analysis defined the latent variable measurement model for the item responses and latent variable regression with demographic and health status covariates (i.e., sex, age group, body weight, self-perceived general health) produced estimates of the magnitude of DIF effects. RESULTS: The CaMos cohort consisted of 9423 respondents; 69.4% were female and 51.7% were less than 65 years. Eight of 10 items on the PF sub-scale and four of five items on the MH sub scale exhibited DIF. Large DIF effects were observed on PF sub-scale items about vigorous and moderate activities, lifting and carrying groceries, walking one block, and bathing or dressing. On the MH sub-scale items, all DIF effects were small or moderate in size. CONCLUSIONS: SF-36 PF and MH sub-scale scores were not comparable across population sub-groups defined by demographic and health status variables due to the effects of DIF, although the magnitude of this bias was not large for most items. We recommend testing and adjusting for DIF to ensure comparability of the SF-36 in population-based investigations. PMID- 26998613 TI - Mossbauer Spectral Properties of Yttrium Iron Garnet, Y3Fe5O12, and Its Isovalent and Nonisovalent Yttrium-Substituted Solid Solutions. AB - Several high-resolution Mossbauer spectra of yttrium iron garnet, Y3Fe5O12, have been fit as a function of temperature with a new model based on a detailed analysis of the spectral changes that result from a reduction from the cubic Ia3d space group to the trigonal R3 space group. These spectral fits indicate that the magnetic sextet arising from the 16a site in cubic symmetry is subdivided into three sextets arising from the 6f, the 3d, 3d, and the 1a, 1b, 2c sites in rhombohedral-axis trigonal symmetry. The 24d site in cubic Ia3d symmetry is subdivided into four sextets arising from four different 6f sites in R3 rhombohedral-axis trigonal symmetry, sites that differ only by the angles between the principal axis of the electric field gradient tensor and the magnetic hyperfine field assumed to be parallel with the magnetic easy axis. This analysis, when applied to the potential nuclear waste storage compounds Y(3 x)Ca(0.5x)Th(0.5x)Fe5O12 and Y(3-x)Ca(0.5x)Ce(0.5x)Fe5O12, indicates virtually no perturbation of the structural, electronic, and magnetic properties upon substitution of small amounts of calcium(II) and thorium(IV) or cerium(IV) onto the yttrium(III) 24c site as compared with Y3Fe5O12. The observed broadening of the four different 6f sites derived from the 24d site results from the substitution of yttrium(III) with calcium(II) and thorium(IV) or cerium(IV) cations on the next-nearest neighbor 24c site. In contrast, the same analysis applied to Y(2.8)Ce(0.2)Fe5O12 indicates a local perturbation of the magnetic exchange pathways as a result of the presence of cerium(IV) in the 24c next nearest neighbor site of the iron(III) 24d site. PMID- 26998612 TI - A Titanium-Organic Framework as an Exemplar of Combining the Chemistry of Metal- and Covalent-Organic Frameworks. AB - A crystalline material with a two-dimensional structure, termed metal-organic framework-901 (MOF-901), was prepared using a strategy that combines the chemistry of MOFs and covalent-organic frameworks (COFs). This strategy involves in situ generation of an amine-functionalized titanium oxo cluster, Ti6O6(OCH3)6(AB)6 (AB = 4-aminobenzoate), which was linked with benzene-1,4 dialdehyde using imine condensation reactions, typical of COFs. The crystal structure of MOF-901 is composed of hexagonal porous layers that are likely stacked in staggered conformation (hxl topology). This MOF represents the first example of combining metal cluster chemistry with dynamic organic covalent bond formation to give a new crystalline, extended framework of titanium metal, which is rarely used in MOFs. The incorporation of Ti(IV) units made MOF-901 useful in the photocatalyzed polymerization of methyl methacrylate (MMA). The resulting polyMMA product was obtained with a high-number-average molar mass (26 850 g mol( 1)) and low polydispersity index (1.6), which in many respects are better than those achieved by the commercially available photocatalyst (P-25 TiO2). Additionally, the catalyst can be isolated, reused, and recycled with no loss in performance. PMID- 26998610 TI - Characterisation of Signalling by the Endogenous GPER1 (GPR30) Receptor in an Embryonic Mouse Hippocampal Cell Line (mHippoE-18). AB - Estrogen can modulate neuronal development and signalling by both genomic and non genomic pathways. Many of its rapid, non-genomic effects on nervous tissue have been suggested to be mediated via the activation of the estrogen sensitive G protein coupled receptor (GPER1 or GPR30). There has been much controversy over the cellular location, signalling properties and endogenous activators of GPER1. Here we describe the pharmacology and signalling properties of GPER1 in an immortalized embryonic hippocampal cell line, mHippoE-18. This cell line does not suffer from the inherent problems associated with the study of this receptor in native tissue or the problems associated with heterologously expression in clonal cell lines. In mHippoE-18 cells, 17beta-Estradiol can mediate a dose-dependent rapid potentiation of forskolin-stimulated cyclic AMP levels but does not appear to activate the ERK1/2 pathway. The effect of 17beta-Estradiol can be mimicked by the GPER1 agonist, G1, and also by tamoxifen and ICI 182,780 which activate GPER1 in a variety of other preparations. The response is not mimicked by the application of the classical estrogen receptor agonists, PPT, (an ERalpha agonist) or DPN, (an ERbeta agonist), further suggesting that this effect of 17beta-Estradiol is mediated through the activation of GPER1. However, after exposure of the cells to the GPER1 specific antagonists, G15 and G36, the stimulatory effects of the above agonists are replaced by dose-dependent inhibitions of forskolin-stimulated cyclic AMP levels. This inhibitory effect is mimicked by aldosterone in a dose-dependent way even in the absence of the GPER1 antagonists. The results are discussed in terms of possible "Biased Antagonism" whereby the antagonists change the conformation of the receptor resulting in changes in the agonist induced coupling of the receptor to different second messenger pathways. PMID- 26998614 TI - Nitrogen-Doped Graphdiyne Applied for Lithium-Ion Storage. AB - The elemental N emerged uniformly in graphdiyne (GDY) after heat treatment under NH3 atmosphere to form N-doping GDY. The interplanar N-GDY distance decreased slightly, which may be ascribed to the smaller atom radius of N than C. Compared with GDY, the introduction of N atoms in N-GDY created numerous heteroatomic defects and active sites, thus achieving enhanced electrochemical properties, including higher reversible capacity, improved rate performance, and superior cycling stability. In addition, N-doping might be advantageous to minimize the surface side reactions and form stable interfaces, hence improving the electrochemical cycling stability of N-GDY electrodes. These results indicate N doping is also an efficient way for improving the electrochemical performance of GDY materials. PMID- 26998617 TI - Rapid Construction of ZnO@ZIF-8 Heterostructures with Size-Selective Photocatalysis Properties. AB - To selectively remove heavy metal from dye solution, inspired by the unique pore structure of ZIF-8, we developed a synthetic strategy for rapid construction of ZnO@ZIF-8 heterostructure photocatalyst for selective reduction of Cr(VI) between Cr(VI) and methylene blue (MB). In particular, ZnO@ZIF-8 core-shell heterostructures were prepared by in situ ZIF-8 crystal growth using ZnO colloidal spheres as template and zinc source within 8-60 min. The shell of the resulting ZnO@ZIF-8 core-shell heterostructure with a uniform thickness of around 30 nm is composed of ZIF-8 crystal polyhedrons. The concentration of organic ligand 2-methylimidazole (Hmim) was found to be crucial for the formation of ZnO@ZIF-8 core-shell heterostructures. Different structures, ZnO@ZIF-8 core-shell spheres and separate ZIF-8 polyhedrons could be formed by altering Hmim concentration, which significantly influences the balance between rate of Zn(2+) release from ZnO and coordinate rate. Importantly, such ZnO@ZIF-8 core-shell heterostructures exhibit size-selective photocatalysis properties due to selective adsorption and permeation effect of ZIF-8 shell. The as-synthesized ZnO@ZIF-8 heterostructures exhibited enhanced selective reduction of Cr(VI) between Cr(VI) and MB, which may find application in the dye industry. This work not only provides a general route for rapid fabrication of such core-shell heterostructures but also illustrates a strategy for selectively enhanced photocatalysis performance by utilizing adsorption and size selectivity of ZIF-8 shell. PMID- 26998615 TI - Bismuth Acetate as a Catalyst for the Sequential Protodeboronation of Di- and Triborylated Indoles. AB - Bismuth(III) acetate is a safe, inexpensive, and selective facilitator of sequential protodeboronations, which when used in conjunction with Ir-catalyzed borylations allows access to a diversity of borylated indoles. The versatility of combining Ir-catalyzed borylations with Bi(III)-catalyzed protodeboronation is demonstrated by selectively converting 6-fluoroindole into products with Bpin groups at the 4-, 5-, 7-, 2,7-, 4,7-, 3,5-, and 2,4,7-positions and the late stage functionalization of sumatriptan. PMID- 26998616 TI - MRI Monitoring of Tumor-Selective Anticancer Drug Delivery with Stable Thermosensitive Liposomes Triggered by High-Intensity Focused Ultrasound. AB - Monitoring of drug release from a heat-activated liposome carrier provides an opportunity for real-time control of drug delivery and allows prediction of the therapeutic effect. We have developed short-chain elastin-like polypeptide incorporating thermosensitive liposomes (STLs). Here, we report the development of STL encapsulating gadobenate dimeglumine (Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL). The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL; however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL. MRI studies showed that the difference in T1 relaxation time between 37 and 42 degrees C for Gd-Dox-STL was larger than the difference for Gd-Dox-LTSL. Although relaxivity for both liposomes at 42 degrees C was similar, the relaxivity of Gd-Dox-STL at 37 degrees C was 2.5-fold lower than that of Gd-Dox-LTSL. This was likely due to Gd-BOPTA leakage from the LTSL because of low stability at 37 degrees C. Pharmacokinetic studies showed plasma half-lives of 4.85 and 1.95 h for Gd-Dox-STL and Gd-Dox-LTSL, respectively, consistent with in vitro stability data. In vivo MRI experiments demonstrated corelease of Dox and Gd-BOPTA from STL under mild hyperthermia induced by high intensity focused ultrasound (HIFU), which suggests STL is a promising tumor selective formulation when coupled with MR-guided HIFU. PMID- 26998618 TI - Modeling Ignition of a Heptane Isomer: Improved Thermodynamics, Reaction Pathways, Kinetics, and Rate Rule Optimizations for 2-Methylhexane. AB - Accurate chemical kinetic combustion models of lightly branched alkanes (e.g., 2 methylalkanes) are important to investigate the combustion behavior of real fuels. Improving the fidelity of existing kinetic models is a necessity, as new experiments and advanced theories show inaccuracies in certain portions of the models. This study focuses on updating thermodynamic data and the kinetic reaction mechanism for a gasoline surrogate component, 2-methylhexane, based on recently published thermodynamic group values and rate rules derived from quantum calculations and experiments. Alternative pathways for the isomerization of peroxy-alkylhydroperoxide (OOQOOH) radicals are also investigated. The effects of these updates are compared against new high-pressure shock tube and rapid compression machine ignition delay measurements. It is shown that rate constant modifications are required to improve agreement between kinetic modeling simulations and experimental data. We further demonstrate the ability to optimize the kinetic model using both manual and automated techniques for rate parameter tunings to improve agreement with the measured ignition delay time data. Finally, additional low temperature chain branching reaction pathways are shown to improve the model's performance. The present approach to model development provides better performance across extended operating conditions while also strengthening the fundamental basis of the model. PMID- 26998619 TI - Anti-Inflammatory Effects of Cajaninstilbene Acid and Its Derivatives. AB - Cajaninstilbene acid (CSA) is one of the active components isolated from pigeon pea leaves. In this study, anti-inflammatory effects of CSA and its synthesized derivatives were fully valued with regard to their activities on the production of nitric oxide (NO) and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in vitro cell model, as well as their impacts on the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae model by live image analysis. Furthermore, the anti inflammatory mechanism of this type of compounds was clarified by western-blot and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that CSA, as well as its synthesized derivatives 5c, 5e and 5h, exhibited strong inhibition activity on the release of NO and inflammatory factor TNF-alpha and IL 6 in lipopolysaccharides (LPS)-stimulated murine macrophages. CSA and 5c greatly inhibited the migration of neutrophils and macrophages in injury zebrafish larvae. CSA and 5c treatment greatly inhibited the phosphorylation of proteins involved in nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that peroxisome proliferator-activated receptor gamma (PPARgamma) inhibitor GW9662 could reverse partly the roles of CSA and 5c, and CSA and 5c treatment greatly resist the decrease of PPARgamma mRNA and protein induced by LPS stimulation. Our results identified the promising anti inflammatory effects of CSA and its derivatives, which may serve as valuable anti inflammatory lead compound. Additionally, the mechanism studies demonstrated that the anti-inflammatory activity of CSA and its derivative is associated with the inhibition of NF-kappaB and MAPK pathways, relying partly on resisting the LPS induced decrease of PPARgamma through improving its expression. PMID- 26998620 TI - Correlates of Trail Use for Recreation and Transportation on 5 Massachusetts Trails. AB - BACKGROUND: Promoting use of community trails is a recommended strategy for increasing population levels of physical activity. Correlates of walking and cycling for recreation or transportation differ, though few studies have compared correlates of trail-based physical activity for recreation and transportation purposes. This study examined associations of demographic, social, and perceived built environmental factors with trail use for recreation and transportation and whether associations were moderated by age, gender, and prior trail use. METHODS: Adults (N = 1195) using 1 of 5 trails in Massachusetts responded to an intercept survey. We used multiple linear and logistic regression models to examine associations with trail use. RESULTS: Respondents' mean age was 44.9 years (standard deviation = 12.5), 55.3% were female, and 82.0% were white. Age (longer term users only), trail use with others, travel time to the trail, and trail design were significantly associated with use for recreation (P < .05). Age, gender, trail safety (longer-term users only), travel time to the trail, trail design (younger users only), and trail beauty were associated with use for transportation (P < .05). CONCLUSIONS: Some common correlates were found for recreational and transportation trail use, whereas some variables were uniquely associated with use for 1 purpose. Tailored strategies are suggested to promote trail use for recreation and transportation. PMID- 26998621 TI - Penimethavone A, a flavone from a gorgonian-derived fungus Penicillium chrysogenum. AB - A novel flavone, penimethavone A (1), possessing a rare unique methyl group at ring-B, was isolated from the fungus Penicillium chrysogenum cultured from a gorgonian Carijoa sp. collected from the South China Sea. The structure was elucidated by extensive spectroscopic analysis and by comparison with related known compound. Compound 1 showed selective and moderate cytotoxicity against cervical cancer (HeLa) and rhabdomyosarcoma cell lines with IC50 values of 8.41 and 8.18 MUM, respectively. PMID- 26998622 TI - Recent advances on biocompatible and biodegradable nanoparticles as gene carriers. AB - INTRODUCTION: Gene therapy mainly depends on the use of appropriate delivery vehicles with no induction of immune responses and toxicity. The limitations of viral gene carriers such as induction of immunogenicity, random integration in the genome of the host, limitations in the size, has led to a movement toward non viral systems with much safer properties. Biodegradable and biocompatible polymeric nanocarriers due to several unique properties such as excellent biocompatibility, prolonged gene circulation time, prevented gene degradation, passive targeting by using the enhanced permeability and retention (EPR) effect, and possibility of modulating polymers structure to obtain desirable therapeutic efficacy, are among the most promising systems for gene delivery. However, biodegradable gene delivery systems have some limitations such as inadequate stability and slow release of therapeutics which have to be overcome. Thus, a variety of advanced functional biodegradable delivery systems with more efficient gene delivery activity has recently been introduced. AREAS COVERED: This review summarizes different aspects of biodegradable and biocompatible nano carriers including formulation, mechanism of intracellular uptake, various potential applications of biodegradable nanoparticles and finally recent studies on the therapeutic efficacy of these nanoparticles in sustained delivery of genes. EXPERT OPINION: Biocompatible and biodegradable polymers will play a necessary and important role in developing new and safe carriers for oligonucleotide delivery. More working and the development of optimized polymers will reveal more their efficacy in the treatment of patients via helping in better gene therapy. PMID- 26998623 TI - Investigational drugs in phase I and phase II clincial trials for the treatment of hospital-acquired pneumonia. AB - INTRODUCTION: Hospital acquired pneumonia (HAP) is one of the main infections acquired by patients during a stay in hospital. The main issue when dealing with patients with HAP and ventilator associated pneumonia (VAP) is the increasing role of multi-drug resistant organisms (MDROs). AREAS COVERED: In this review the authors summarize the actual situation of MDROs as a cause of HAP and VAP. They also review the current treatment options stated in the most important international guidelines. Finally, they focus on the investigational drugs that have reached the phase III stage of development and the novel compounds that are being studied in phase I and II clinical trials. EXPERT OPINION: Thanks to their excellent activity against MDROs, drugs in development for the treatment of HAP and VAP can significantly improve the therapeutic options available. In selected patients, the possibility to administer directed therapy with monoclonal antibodies to specific pathogens is an exciting strategy in the fight against widespread resistance. PMID- 26998624 TI - Voluntary community service in medical school: A qualitative study on student leaders' motivations, experiences, and outcomes. AB - BACKGROUND: Participation in community service within underprivileged communities among medical students is associated with numerous positive outcomes, such as promoting empathy, enhancing leadership qualities, and fostering civic and social responsibility. We conducted a qualitative study to understand the experiences, motivations and student-reported outcomes on personal growth, when medical students in a developed Asian country participate in local and overseas community services. METHODS: We recruited medical students from Yong Loo Lin School of Medicine (YLLSOM), National University of Singapore, who were leaders of a community service project organized in medical school. Twelve one-to-one interviews were held for the participants from 6 to 8 January 2013. Interviews were audio-recorded and transcribed into free-flow text. Thematic analysis was performed independently by three researchers. RESULTS: Motivations to participate in community service include past-positive community service experience and present motivations such as compassion, self-discovery etc. Students reported higher empathy levels, improved communication, organization, decision-making, interpersonal, and leadership skills. The degree of influence on academic work and residency choice were varied. CONCLUSION: Community service in medical school enriches medical students by bringing about improved self-reported outcomes, leadership skills, and interpersonal skills. It has some bearing on residency choice and academic work. PMID- 26998625 TI - Calcium plays a key role in paraoxon-induced apoptosis in EL4 cells by regulating both endoplasmic reticulum- and mitochondria-associated pathways. AB - CONTEXT AND OBJECTIVE: Paraoxon (POX) is one of the most toxic organophosphorus pesticides, but its toxic mechanisms associated with apoptosis remain unclear. The aim of this study was to investigate calcium-associated mechanisms in POX induced apoptosis in EL4 cells. MATERIALS AND METHODS: EL4 cells were exposed to POX for 0-16 h. EGTA was used to chelate Ca(2+ ) in extracellular medium, and heparin and procaine were used to inhibit Ca(2+ )efflux from the endoplasmic reticulum (ER). Z-ATAD-FMK was used to inhibit caspase-12 activity. The apoptotic rate assay, western blotting and immunocytochemistry (ICC) were used to reveal the mechanisms of POX-induced apoptosis. RESULTS AND DISCUSSION: POX significantly increased the expression and activation of caspase-12 and caspase 3, enhanced expression of calpain 1 and calpain 2, and induced the release of cyt c, but did not change the expression of Grp 78. Inhibiting caspase-12 activity alleviated POX-induced upregulation of calpain 1 and caspase-3, promoted POX induced upregulation of calpain 2, and reduced POX-induced cyt c release, suggesting that there was a cross-talk between the ER-associated pathway and mitochondria-associated apoptotic signals. Attenuating intracellular calcium concentration with EGTA, heparin or procaine decreased POX-induced upregulation of calpain 1, calpain 2, caspase-12 and caspase-3, and reduced POX-induced cyt c release. After pretreatment with EGTA or procaine, POX significantly promoted expression of Grp 78. CONCLUSIONS: Calcium played a key role in POX-induced apoptosis in EL4 cells by regulating both ER- and mitochondria-associated pathways. The cross-talk of ER- and mitochondria-associated pathways was accomplished through calcium signal. PMID- 26998626 TI - Further increased production of free fatty acids by overexpressing a predicted transketolase gene of the pentose phosphate pathway in Aspergillus oryzae faaA disruptant. AB - Free fatty acids are useful as source materials for the production of biodiesel fuel and various chemicals such as pharmaceuticals and dietary supplements. Previously, we attained a 9.2-fold increase in free fatty acid productivity by disrupting a predicted acyl-CoA synthetase gene (faaA, AO090011000642) in Aspergillus oryzae. In this study, we achieved further increase in the productivity by overexpressing a predicted transketolase gene of the pentose phosphate pathway in the faaA disruptant. The A. oryzae genome is predicted to have three transketolase genes and overexpression of AO090023000345, one of the three genes, resulted in phenotypic change and further increase (corresponding to an increased production of 0.38 mmol/g dry cell weight) in free fatty acids at 1.4-fold compared to the faaA disruptant. Additionally, the biomass of hyphae increased at 1.2-fold by the overexpression. As a result, free fatty acid production yield per liter of liquid culture increased at 1.7-fold by the overexpression. PMID- 26998627 TI - Oxazolidinone antimicrobials: a patent review (2012-2015). AB - INTRODUCTION: Antimicrobial resistance in Gram-positive bacteria is a major health care issue. This review summarizes patent publications from 2012 to 2015 that divulged novel oxazolidinones as antibacterial agents. AREAS COVERED: A total of 25 patents obtained from Espacenet, WIPO Patentscope and FreePatentsOnline, and AcclaimIP search engines were reviewed. The patents were scrutinized based on the novelty of the compounds, their antibacterial activity (MIC, ug/mL), and the process of preparation. The oxazolidinones with promising antibacterial activity were classified according to the following structural diversities, as biaryl heterocyclic, fused heteroaryl rings containing oxazolidinones, and others. The biaryl heterocyclic, fused heteroaryl, benzoxazine, and the 1H-pyrazol-1-yl containing oxazolidinone derivatives demonstrated potent antibacterial activities superior to linezolid against Gram positive bacteria. Some derivatives were effective against standard strains of Gram-negative bacteria, namely Moraxella catarrhalis ATCC A894, and Escherichia coli ATCC 25922. In addition, a patent disclosed a structural isomer of linezolid with marginal activity against the aerobic Gram-negative bacteria MDR Stenotrophomonas (Xanthomonas) maltophilia, while linezolid and vancomycin did not inhibit growth. Finally, some derivatives showed activity against respiratory infectious diseases' causative agents, such as B. anthracis, B. mallei, Y. pestis, and M. pneumoniae. EXPERT OPINION: Overall, there is limited in vivo data to support the potential clinical advancement of the currently reported novel derivatives. PMID- 26998629 TI - Molecular Phylogenetic Analysis of Infidum similis, Including Morphological Data and Estimation of its Genome Size. AB - : Infidum similis Travassos, 1916 (Dicrocoeliidae: Leipertrematinae) was found in the gall bladder of Leptophis diplotropis Gunther, 1872 from El Podrido, Acapulco, Guerrero, Mexico. A phylogenetic analysis based on partial sequences of the 28S ribosomal RNA using maximum likelihood (ML) and Bayesian inference (BI) analyses was carried out to assess its phylogenetic position within suborder Xiphidiata, alongside members of the superfamilies Gorgoderoidea and Plagiorchoidea. The phylogenetic trees showed that the genus is most-closely related to the Plagiorchoidea rather than to the Gorgoderoidea, in keeping with previous taxonomic designations. Phylogenies obtained from ML and BI analysis of the 28S rDNA gene revealed a well supported clade in which Choledocystus hepaticus (Lutz, 1928) Sullivan, 1977 is sister to I. similis. On the other hand, a tree obtained using a partial sequence of the cytochrome c oxidase subunit 1 (cox1) mtDNA gene (ML and BI analysis), with species supposed to be closely related to I. similis according to 28S, does not support this relatedness. Based on the independence of Infidum from the subfamily Leipertrematinae Yamaguti, 1958 , our results clearly demonstrated that the genus corresponds to a different family and with species closely related to C. hepaticus within Plagiorchoidea. New data are presented about the tegumental surface of I. similis by scanning electron microscopy as well as the estimation of its haploid genome size using Feulgen Image Analysis Densitometry of sperm nuclei as part of the characterization of this species. This is the first genome size estimated for a member of Plagiorchiida, and these data will provide a new source of knowledge on helminth diversity and evolutionary studies. This constitutes the first host record, and new geographical distribution, for this species in Mexico. PMID- 26998628 TI - Endoscopic Complete Remission of Crohn Disease After Anti-Tumor Necrosis Factor alpha Therapy: CT Enterographic Findings and Their Clinical Implications. AB - OBJECTIVE: The purpose of this study was to describe the CT enterographic (CTE) findings after endoscopic complete remission (CR) of Crohn disease in patients treated with anti-tumor necrosis factor-alpha (anti-TNF-alpha) and the clinical implications of these findings. MATERIALS AND METHODS: The records of 27 patients with Crohn disease (14 men, 13 women; mean age, 28.4 +/- 8.6 [SD] years) who achieved endoscopic (ileocolonoscopic) CR after anti-TNF-alpha therapy and underwent CTE both before therapy and at endoscopic CR were identified. Two readers independently assessed the frequencies and severities of mural and perienteric CTE abnormalities, generally regarded as active inflammatory findings, in the terminal ileum and colorectum in the endoscopic CR state and compared them with the corresponding findings before anti-TNF-alpha therapy. The association between the presence of CTE abnormalities in the face of endoscopic CR and patient outcome during subsequent follow-up was investigated. RESULTS: CTE abnormalities were present in the face of endoscopic CR in 11-18 (26-42%) of 43 bowel sections (18 terminal ileum, 25 colorectum), the most frequent being mural hyperenhancement (21-40%) followed by mural thickening (12-16%). Both findings were mild and unaccompanied by other findings. The frequency and severity of mural and perienteric CTE abnormalities were statistically significantly reduced at endoscopic CR compared with the pre-treatment state. Patients with (n = 10) and without (n = 17) CTE abnormalities at endoscopic CR did not significantly differ with respect to Crohn disease aggravation during subsequent follow-up periods averaging 27.4 and 28.5 months (0/10 versus 2/17, p = 0.516). CONCLUSION: More than one-fourth of bowel sections in endoscopic CR after anti-TNF-alpha therapy had residual CTE abnormalities, predominantly mild mural thickening or hyperenhancement. These findings may not have any clinical significance. PMID- 26998630 TI - Learning spinal manipulation: A best-evidence synthesis of teaching methods. AB - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of different reported methods used to teach spinal manipulative therapy to chiropractic students. METHODS: For this best-evidence literature synthesis, 5 electronic databases were searched from 1900 to 2015. Eligible studies were critically appraised using the criteria of the Scottish Intercollegiate Guidelines Network. Scientifically admissible studies were synthesized following best-evidence synthesis principles. RESULTS: Twenty articles were critically appraised, including 9 randomized clinical trials, 9 cohort studies, and 2 systematic reviews/meta-analyses. Eleven articles were accepted as scientifically admissible. The type of teaching method aids included a Thrust in Motion cervical manikin, instrumented cardiopulmonary reanimation manikin, padded contact with a load cell, instrumented treatment table with force sensor/transducer, and Dynadjust instrument. CONCLUSIONS: Several different methods exist in the literature for teaching spinal manipulative therapy techniques; however, future research in this developing area of chiropractic education is proposed. It is suggested that various teaching methods be included in the regular curricula of chiropractic colleges to aid in developing manipulation skills, efficiency, and knowledge of performance. PMID- 26998631 TI - Assessment of Chiari Malformation Type I Before and After Surgery. PMID- 26998633 TI - Outbreak of Zika virus disease in the Americas and the association with microcephaly, congenital malformations and Guillain-Barre syndrome. PMID- 26998632 TI - Epidemiology of children with head injury: a national overview. AB - BACKGROUND: The National Confidential Enquiry describes the epidemiology of children admitted to hospital with head injury. METHOD: Children (<15 years old) who died or were admitted for >4 h with head injury were identified from 216 UK hospitals (1 September 2009 to 28 February 2010). Data were collected using standard proformas and entered on to a database. A descriptive analysis of the causal mechanisms, child demographics, neurological impairment, CT findings, and outcome at 72 h are provided. RESULTS: Details of 5700 children, median age 4 years (range 0-14.9 years), were analysed; 1093 (19.2%) were <1 year old, 3500 (61.4%) were boys. There was a significant association of head injury with social deprivation 39.7/100 000 (95% CI 37.0 to 42.6) in the least deprived first quintile vs. 55.1 (95% CI 52.1 to 58.2) in the most deprived fifth quintile (p<0.01). Twenty-four children died (0.4%). Most children were admitted for one night or less; 4522 (79%) had a Glasgow Coma Scale score of 15 or were Alert (on AVPU (Alert, Voice, Pain, Unresponsive)). The most common causes of head injury were falls (3537 (62.1%); children <5 years), sports-related incidents (783 (13.7%); median age 12.4 years), or motor vehicle accidents (MVAs) (401 (7.1%); primary-school-aged children). CT scans were performed in 1734 (30.4%) children; 536 (30.9%) were abnormal (skull fracture and/or intracranial injury or abnormality): 269 (7.6%) were falls, 82 (10.5%) sports related and 100 (25%). A total of 357 (6.2%) children were referred to social care because of child protection concerns (median age 9 months (range 0-14.9 years)). CONCLUSIONS: The data described highlight priorities for targeted age-specific head injury prevention and have the potential to provide a baseline to evaluate the effects of regional trauma networks (2012) and National Institute of Health and Care Excellence (NICE) head injury guidelines (2014), which were revised after the study was completed. PMID- 26998634 TI - Removal of radioactive contaminants by polymeric microspheres. AB - Radionuclide removal from radioactive liquid waste by adsorption on polymeric microspheres is the latest application of polymers in waste management. Polymeric microspheres have significant immobilization capacity for ionic substances. A laboratory study was carried out by using poly(N-isopropylacrylamide) for encapsulation of radionuclide in the liquid radioactive waste. There are numbers of advantages to use an encapsulation technology in radioactive waste management. Results show that polymerization step of radionuclide increases integrity of solidified waste form. Test results showed that adding the appropriate polymer into the liquid waste at an appropriate pH and temperature level, radionuclide was encapsulated into polymer. This technology may provide barriers between hazardous radioactive ions and the environment. By this method, solidification techniques became easier and safer in nuclear waste management. By using polymer microspheres as dust form, contamination risks were decreased in the nuclear industry and radioactive waste operations. PMID- 26998636 TI - [Long-term trends in the metabolic profile test results in German Holstein dairy herds in Thuringia, Germany]. AB - OBJECTIVE: Systematic metabolic profile tests at regular intervals provide important information to meet the increasing challenges in managing dairy herds. This study aimed at deriving long-term trends from the results of metabolic profile tests in Thuringian German Holstein dairy herds. MATERIAL AND METHODS: Blood and urine samples were collected from 710 fresh, high yielding, and dry cows, respectively, to monitor 13 parameters including the serum non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), bilirubin, beta-carotene and urea concentrations, the serum of aspartate aminotransferase and glutamate dehydrogenase activities, the serum concentrations of the minerals calcium, inorganic phosphate and selenium, the urine potassium and sodium concentrations, and the net acid-base excretion (NABE). A total of 17,070 group samples from 103 herds were collected during 1997-2014. Period prevalence of aberrant groups was calculated for each parameter and year accordingly. Using a linear regression model, a long-term trend of the period prevalence was determined. RESULTS: To account for the 15 aberrancies possible for each stage of lactation, seven significant trends were found for dry, nine for fresh, and ten for lactating cows. A decrease of the period prevalence was detected for increased NEFA, for low serum beta-carotene, selenium, inorganic phosphate, and urea concentrations, for low sodium and high potassium urine concentrations, and for increased NABE. In contrast, period prevalence increased significantly for cases with increased serum aspartate aminotransferase and glutamate dehydrogenase activities, increased bilirubin concentration, and low NABE. CONCLUSION AND CLINICAL RELEVANCE: Metabolic profile tests enable a description of the herd health status using objectively measured data as a basis for the implementation of measures to optimize herd management to improve the herd health status. PMID- 26998637 TI - Correlation between the Selectivity and the Structure of an Asymmetric Catalyst Built on a Chirally Amplified Supramolecular Helical Scaffold. AB - For the first time, supramolecular helical rods composed of an achiral metal complex and a complementary enantiopure monomer provided a good level of enantioinduction in asymmetric catalysis. Mixtures containing an achiral ligand monomer (BTA(PPh2), 2 mol %) and an enantiopure ligand-free comonomer (ester BTA, 2.5 mol %), both possessing a complementary benzene-1,3,5-tricarboxamide (BTA) central unit, were investigated in combination with [Rh(cod)2]BArF (1 mol %) in the asymmetric hydrogenation of dimethyl itaconate. Notably, efficient chirality transfer occurs within the hydrogen-bonded coassemblies formed by BTA Ile and the intrinsically achiral catalytic rhodium catalyst, providing the hydrogenation product with up to 85% ee. The effect of the relative content of BTA Ile as compared to the ligand was investigated. The amount of chiral comonomer can be decreased down to one-fourth of that of the ligand without deteriorating the enantioselectivity of the reaction, while the enantioselectivity decreases for mixtures containing high amounts of BTA Ile. The nonlinear relationship between the amount of chiral comonomer and the enantioselectivity indicates that chirality amplification effects are at work in this catalytic system. Also, right handed helical rods are formed upon co-assembly of the achiral rhodium complex of BTA(PPh2) and the enantiopure comonomer BTA Ile as confirmed by various spectroscopic and scattering techniques. Remarkably, the major enantiomer and the selectivity of the catalytic reaction are related to the handedness and the net helicity of the coassemblies, respectively. Further development of this class of catalysts built on chirally amplified helical scaffolds should contribute to the design of asymmetric catalysts operating with low amounts of chiral entities. PMID- 26998638 TI - La(1-x)Bi(1+x)S3 (x ~ 0.08): An n-Type Semiconductor. AB - The new bismuth chalcogenide La(0.92)Bi(1.08)S3 crystallizes in the monoclinic space group C2/m with a = 28.0447(19) A, b = 4.0722(2) A, c = 14.7350(9) A, and beta = 118.493(5) degrees . The structure of La(0.92)Bi(1.08)S3 is built of NaCl type Bi2S5 blocks and BiS4 and LaS5 infinitely long chains, forming a compact three-dimensional framework with parallel tunnels. Optical spectroscopy and resistivity measurements reveal a semiconducting behavior with a band gap of ~1 eV and activation energy for transport of 0.36(1) eV. Thermopower measurements suggest the majority carriers of La(0.92)Bi(1.08)S3 are electrons. Heat capacity measurements indicate no phase transitions from 2 to 300 K. Band structure calculations at the density functional theory level confirm the semiconducting nature and the indirect gap of La(0.92)Bi(1.08)S3. PMID- 26998639 TI - Electrically Tunable Quenching of DNA Fluctuations in Biased Solid-State Nanopores. AB - Nanopores offer sensors for a broad range of nanoscale materials, in particular ones of biological origin such as single- and double-stranded DNA or DNA-protein complexes. In order to increase single-molecule sensitivity, it is desirable to control biomolecule motion inside nanopores. In the present study, we investigate how in the case of a double-stranded DNA the single-molecule sensitivity can be improved through bias voltages. For this purpose we carry out molecular dynamics simulations of the DNA inside nanopores in an electrically biased metallic membrane. Stabilization of DNA, namely, a reduction in thermal fluctuations, is observed under positive bias voltages, while negative voltages bring about only negligible stabilization. For positive biases the stabilization arises from electrostatic attraction between the negatively charged DNA backbone and the positively charged pore surface. Simulations on a teardrop-shaped pore show a transverse shift of DNA position toward the sharp end of the pore under positive bias voltages, suggesting the possibility to control DNA alignment inside nanopores through geometry shaping. The present findings open a feasible and efficient route to reduce thermal noise and, in turn, enhance the signal-to-noise ratio in single-molecule nanopore sensing. PMID- 26998640 TI - Financial strain, trajectories of marital processes, and African American newlyweds' marital instability. AB - The present study examined the longitudinal associations among financial strain, trajectories of marital processes, and increases in marital instability concerns among a sample of 280 African American newlywed couples followed over the first 3 years of marriage. Results from dyadic structural equation modeling revealed that financial strain experienced during the early years of marriage was associated with increased marital instability concerns for both husbands and wives. Latent growth curves of marital processes revealed mean declines in appraisals of spousal warmth and increases in appraisals of spousal hostility, with variability between individuals in rates of decline in warmth; further, wives' appraisals of spousal warmth covaried with levels of financial strain, such that high levels of financial strain were associated with steeper declines in spousal warmth appraisals. For both husbands and wives, rates of change in spousal warmth appraisals had a greater influence on increases in marital instability concerns than either starting levels of spousal warmth appraisals or financial strain. Findings highlight the long-term associations between external stress and trajectories of marital appraisals as well as their relative effects on marital distress. (PsycINFO Database Record PMID- 26998641 TI - Effect of Water Vapor Adsorption on Electrical Properties of Carbon Nanotube/Nanocrystalline Cellulose Composites. AB - It has been long known that the electrical properties of cellulose are greatly influenced by adsorption of water vapor. Incorporating conductive nanofillers in a cellulose matrix is an example of an approach to tailor their characteristics for use in electronics and sensing devices. In this work, we introduce two new nanocomposites comprising carbon nanotubes (CNTs) and conventional or electrosterically stabilized nanocrystalline celluloses matrices. While conventional nanocrystalline cellulose (NCC) consists of a rigid crystalline backbone, electrosterically stabilized cellulose (ENCC) is composed of a rigid crystalline backbone with carboxylated polymers protruding from both ends. By tuning CNT loading, we can tailor a CNT/NCC composite with minimal electrical sensitivity to the ambient relative humidity, despite the fact that the composite has a high moisture uptake. The expected decrease in CNT conductivity upon water vapor adsorption, due to electron donation, is counterbalanced by an increase in the conductivity of NCC due to proton hopping at an optimum CNT loading (1-2%). Contrary to the CNT/NCC composite, a CNT/ENCC composite at 1% CNT loading shows insulating behavior for relative humidities up to 75%, after which the composite becomes conductive. This interesting behavior can be ascribed to the low moisture uptake of ENCC at low and moderate relative humidities due to the limited number of hydroxyl groups and hydrogen bond formation between carboxyl groups on ENCC, which endow ENCC with limited water molecule adsorption sites. PMID- 26998642 TI - Structural Changes Associated with Transthyretin Misfolding and Amyloid Formation Revealed by Solution and Solid-State NMR. AB - Elucidation of structural changes involved in protein misfolding and amyloid formation is crucial for unraveling the molecular basis of amyloid formation. Here we report structural analyses of the amyloidogenic intermediate and amyloid aggregates of transthyretin using solution and solid-state nuclear magnetic resonance (NMR) spectroscopy. Our solution NMR results show that one of the two main beta-sheet structures (CBEF beta-sheet) is maintained in the aggregation competent intermediate, while the other DAGH beta-sheet is more flexible on millisecond time scales. Magic-angle-spinning solid-state NMR revealed that AB loop regions interacting with strand A in the DAGH beta-sheet undergo conformational changes, leading to the destabilized DAGH beta-sheet. PMID- 26998644 TI - pH-Triggered Surface Charge Reversed Nanoparticle with Active Targeting To Enhance the Antitumor Activity of Doxorubicin. AB - PLGA nanoparticles are widely used in tumor targeting drug delivery systems. However, the naked PLGA nanoparticles (NNPs) not only have low drug loading but also can be rapidly removed from blood circulation by the immune system. The aim of this study was to prepare pH-triggered surface charge reversed lipid hybrid PLGA nanoparticles (LNPs) to enhance drug loading and drug delivery efficiency. CHO-Arg-His-OMe and FA-PEG-DSPE were synthesized to modify PLGA nanoparticles to prepare LNPs. The drug loading and encapsulation rate of LNPs were greatly improved as compared with NNPs. In pH 7.4 medium, doxorubicin (DOX)-loaded LNPs showed negative charge and released DOX slowly. In pH 5.0 medium, DOX-loaded LNPs exhibited positive charge and released DOX quickly. DOX-loaded LNPs delivered more DOX to the nucleus of KB cells and MBA-MD-231/ADR cells than did free DOX. In addition, DOX-loaded LNPs significantly inhibited the proliferation of KB cells and MBA-MD-231/ADR cells. Compared with free DOX, the same dose of the DOX loaded LNPs delivered more DOX to tumor tissue. Thus, DOX-loaded LNPs significantly inhibited the growth of tumor in tumor-bearing nude mice and obviously reduced the systemic toxicity of DOX. In conclusion, pH-triggered surface charge reversed DOX-loaded LNPs significantly enhanced the antitumor activity of DOX in vitro and in vivo. DOX-loaded LNPs had great potential in tumor targeted chemotherapy. PMID- 26998643 TI - Ulbactins F and G, Polycyclic Thiazoline Derivatives with Tumor Cell Migration Inhibitory Activity from Brevibacillus sp. AB - Two new structurally unique compounds bearing a nitrogen- and sulfur-containing tricyclic ring system, ulbactin F (1) and its diastereomeric isomer ulbactin G (2), were isolated from the culture extract of a sponge-derived Brevibacillus sp. The structures and absolute configurations of 1 and 2 were determined by NMR analysis and X-ray crystallographic analysis. These compounds inhibit the migration of tumor cells in the submicromolar to micromolar range. PMID- 26998645 TI - Physical Therapy and Hospitalization Among Medicare Beneficiaries With Low Back Pain: A Retrospective Cohort Study. AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study was to evaluate associations between receipt and quantity of outpatient physical therapy (PT) during an episode of care and 30-day and 180-day hospital admissions for any condition and lumbar spine conditions. SUMMARY OF BACKGROUND DATA: Low back pain (LBP) is a common cause of hospitalization and the most common reason Medicare beneficiaries utilize outpatient PT. The association between PT and hospitalization among patients with LBP is unknown. METHODS: A national sample of Medicare Fee-for-Service claims included 413,608 beneficiaries with an International Classification of Disease 9th revision (ICD-9) code of LBP and 1,415,037 episodes of care between June 1, 2010, and June 30, 2011. Episodes were classified as PT episodes or non-PT episodes. Relative risk of hospitalization from the episode start date was caldulated, adjusting for health status (Charlson comorbidity index), prior care utilization (number of prior hospitalizations and total number of episodes), an indicator of LBP severity (number of LBP ICD-9 codes), and demographics (sex, race/ethnicity, age). RESULTS: The proportion of 30-day hospitalization for any condition was 3.42% for PT episodes of care and 6.54% for non-PT episodes. For 180-day hospitalization, proportions were 15.45% (PT) and 21.65% (non-PT). The adjusted relative risk reduction of PT (vs. non-PT) was 41% for 30 days [99% confidence interval (CI) 38-44] and 22% for 180 days (20 24). For admitting diagnoses of lumbar spine, reductions were 65% at 30 days and 32% at 180 days. More PT treatment days showed greater 30-day risk reductions. For any condition, compared with non-PT, reductions were 24% for 1 to 2 treatment days (lowest tertile), 45% for 3 to 7 days, and 65% for more than 8 days (highest tertile). Stronger effects were found for lumbar spine admissions. Associations between PT quantity and 180-day hospitalization were less consistent. Limitations of Medicare claims include the potential for inaccuracies, limited knowledge about disease severity, and which PT interventions were conducted. CONCLUSION: Receipt of PT during an episode had a 22% to 65% reduced relative risk of hospitalization, with greater short-term reductions for more PT treatment days. LEVEL OF EVIDENCE: 3. PMID- 26998646 TI - Tunable Diffractive Optical Elements Based on Shape-Memory Polymers Fabricated via Hot Embossing. AB - We introduce actively tunable diffractive optical elements fabricated from shape memory polymers (SMPs). By utilizing the shape-memory effect of the polymer, at least one crucial attribute of the diffractive optical element (DOE) is tunable and adjustable subsequent to the completed fabrication process. A thermoplastic, transparent, thermoresponsive polyurethane SMP was structured with diverse diffractive microstructures via hot embossing. The tunability was enabled by programming a second, temporary shape into the diffractive optical element by mechanical deformation, either by stretching or a second embossing cycle at low temperatures. Upon exposure to the stimulus heat, the structures change continuously and controllable in a predefined way. We establish the novel concept of shape-memory diffractive optical elements by illustrating their capabilities, with regard to tunability, by displaying the morphing diffractive pattern of a height tunable and a period tunable structure, respectively. A sample where an arbitrary structure is transformed to a second, disparate one is illustrated as well. To prove the applicability of our tunable shape-memory diffractive optical elements, we verified their long-term stability and demonstrated the precise adjustability with a detailed analysis of the recovery dynamics, in terms of temperature dependence and spatially resolved, time-dependent recovery. PMID- 26998647 TI - Cerebral Gaseous Microemboli are Detectable During Continuous Venovenous Hemodialysis in Critically Ill Patients: An Observational Pilot Study. AB - BACKGROUND: Continuous venovenous hemodialysis (CVVHD) may generate microemboli that cross the pulmonary circulation and reach the brain. The aim of the present study was to quantify (load per time interval) and qualify (gaseous vs. solid) cerebral microemboli (CME), detected as high-intensity transient signals, using transcranial Doppler ultrasound. MATERIALS AND METHODS: Twenty intensive care unit (ICU group) patients requiring CVVHD were examined. CME were recorded in both middle cerebral arteries for 30 minutes during CVVHD and a CVVHD-free interval. Twenty additional patients, hospitalized for orthopedic surgery, served as a non-ICU control group. Statistical analyses were performed using the Mann Whitney U test or the Wilcoxon matched-pairs signed-rank test, followed by Bonferroni corrections for multiple comparisons. RESULTS: In the non-ICU group, 48 (14.5-169.5) (median [range]) gaseous CME were detected. In the ICU group, the 67.5 (14.5-588.5) gaseous CME detected during the CVVHD-free interval increased 5 fold to 344.5 (59-1019) during CVVHD (P<0.001). The number of solid CME was low in all groups (non-ICU group: 2 [0-5.5]; ICU group CVVHD-free interval: 1.5 [0 14.25]; ICU group during CVVHD: 7 [3-27.75]). CONCLUSIONS: This observational pilot study shows that CVVHD was associated with a higher gaseous but not solid CME burden in critically ill patients. Although the differentiation between gaseous and solid CME remains challenging, our finding may support the hypothesis of microbubble generation in the CVVHD circuit and its transpulmonary translocation toward the intracranial circulation. Importantly, the impact of gaseous and solid CME generated during CVVHD on brain integrity of critically ill patients currently remains unknown and is highly debated. PMID- 26998648 TI - Noninvasive Hemodynamic Measurements During Neurosurgical Procedures in Sitting Position. AB - BACKGROUND: Neurosurgical procedures in sitting position need advanced cardiovascular monitoring. Transesophageal echocardiography (TEE) to measure cardiac output (CO)/cardiac index (CI) and stroke volume (SV), and invasive arterial blood pressure measurements for systolic (ABPsys), diastolic (ABPdiast) and mean arterial pressure (MAP) are established monitoring technologies for these kind of procedures. A noninvasive device for continuous monitoring of blood pressure and CO based on a modified Penaz technique (volume-clamp method) was introduced recently. In the present study the noninvasive blood pressure measurements were compared with invasive arterial blood pressure monitoring, and the noninvasive CO monitoring to TEE measurements. METHODS: Measurements of blood pressure and CO were performed in 35 patients before/after giving a fluid bolus and a change from supine to sitting position, start of surgery, and repositioning from sitting to supine at the end of surgery. Data pairs from the noninvasive device (Nexfin HD) versus arterial line measurements (ABPsys, ABPdiast, MAP) and versus TEE (CO, CI, SV) were compared using Bland-Altman analysis and percentage error. RESULTS: All parameters compared (CO, CI, SV, ABPsys, ABPdiast, MAP) showed a large bias and wide limits of agreement. Percentage error was above 30% for all parameters except ABPsys. CONCLUSION: The noninvasive device based on a modified Penaz technique cannot replace arterial blood pressure monitoring or TEE in anesthetized patients undergoing neurosurgery in sitting position. PMID- 26998649 TI - How Ultrasonographic Measurement of Optic Nerve Sheath Diameter (ONSD) Aids in Diagnosis of Cerebrovascular Accident in a Patient on Ventilator? PMID- 26998650 TI - Effects of Prone Position and Positive End-Expiratory Pressure on Noninvasive Estimators of ICP: A Pilot Study. AB - BACKGROUND: Prone positioning and positive end-expiratory pressure can improve pulmonary gas exchange and respiratory mechanics. However, they may be associated with the development of intracranial hypertension. Intracranial pressure (ICP) can be noninvasively estimated from the sonographic measurement of the optic nerve sheath diameter (ONSD) and from the transcranial Doppler analysis of the pulsatility (ICPPI) and the diastolic component (ICPFVd) of the velocity waveform. METHODS: The effect of the prone positioning and positive end expiratory pressure on ONSD, ICPFVd, and ICPPI was assessed in a prospective study of 30 patients undergoing spine surgery. One-way repeated measures analysis of variance, fixed-effect multivariate regression models, and receiver operating characteristic analyses were used to analyze numerical data. RESULTS: The mean values of ONSD, ICPFVd, and ICPPI significantly increased after change from supine to prone position. Receiver operating characteristic analyses demonstrated that, among the noninvasive methods, the mean ONSD measure had the greatest area under the curve signifying it is the most effective in distinguishing a hypothetical change in ICP between supine and prone positioning (0.86+/-0.034 [0.79 to 0.92]). A cutoff of 0.43 cm was found to be a best separator of ONSD value between supine and prone with a specificity of 75.0 and a sensitivity of 86.7. CONCLUSIONS: Noninvasive ICP estimation may be useful in patients at risk of developing intracranial hypertension who require prone positioning. PMID- 26998651 TI - The Use of Intracranial Doppler as a Cause for Intraoperative Hyperthermia. PMID- 26998652 TI - The Pathophysiology of Early Hypotension Following Epinephrine-containing Local Anesthetic Infiltration of the Nasal Mucosa in Patients Undergoing Endoscopic Transsphenoidal Hypophysectomy: A Prospective, Observational Study. AB - In patients undergoing endoscopic transsphenoidal hypophysectomy, the nasal mucosa is often infiltrated with local anesthetic solutions that contain epinephrine to aid hemostasis. This may, however, result in hemodynamic changes, especially hypotension. We characterized the cardiovascular changes using a LiDCOrapid monitor in 13 patients after the infiltration of 4% articaine containing 1:200,000 epinephrine. Nine (69%) had a >20% decrease in mean arterial pressure at a median time of 116 seconds after the infiltration of articaine with epinephrine. Analysis of the cardiac output data revealed that this was caused by a sustained reduction in systemic vascular resistance. The arterial blood pressure normalized over a period of 60 to 90 seconds secondary to increases in stroke volume and heart rate producing an elevation in cardiac output. Transient hypotension following the infiltration of epinephrine-containing local anesthetics may be caused by epinephrine stimulation of beta2-adrenoceptors producing vasodilation. PMID- 26998654 TI - Structural Dissection of the Active Site of Thermotoga maritima beta Galactosidase Identifies Key Residues for Transglycosylating Activity. AB - Glycoside hydrolases, specifically beta-galactosidases, can be used to synthesize galacto-oligosaccharides (GOS) due to the transglycosylating (secondary) activity of these enzymes. Site-directed mutagenesis of a thermoresistant beta galactosidase from Thermotoga maritima has been carried out to study the structural basis of transgalactosylation and to obtain enzymatic variants with better performance for GOS biosynthesis. Rational design of mutations was based on homologous sequence analysis and structural modeling. Analysis of mutant enzymes indicated that residue W959, or an alternative aromatic residue at this position, is critical for the synthesis of beta-3'-galactosyl-lactose, the major GOS obtained with the wild-type enzyme. Mutants W959A and W959C, but not W959F, showed an 80% reduced synthesis of this GOS. Other substitutions, N574S, N574A, and F571L, increased the synthesis of beta-3'-galactosyl-lactose about 40%. Double mutants F571L/N574S and F571L/N574A showed an increase of about 2-fold. PMID- 26998653 TI - Long-Term Survival, Quality of Life, and Quality-Adjusted Survival in Critically Ill Patients With Cancer. AB - OBJECTIVES: To assess the long-term survival, health-related quality of life, and quality-adjusted life years of cancer patients admitted to ICUs. DESIGN: Prospective cohort. SETTING: Two cancer specialized ICUs in Brazil. PATIENTS: A total of 792 participants. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The health-related quality of life before ICU admission; at 15 days; and at 3, 6, 12, and 18 months was assessed with the EQ-5D-3L. In addition, the vital status was assessed at 24 months. The mean age of the subjects was 61.6 +/- 14.3 years, 42.5% were female subjects and half were admitted after elective surgery. The mean Simplified Acute Physiology Score 3 was 47.4 +/- 15.6. Survival at 12 and 18 months was 42.4% and 38.1%, respectively. The mean EQ-5D-3L utility measure before admission to the ICU was 0.47 +/- 0.43, at 15 days it was 0.41 +/- 0.44, at 90 days 0.56 +/- 0.42, at 6 months 0.60 +/- 0.41, at 12 months 0.67 +/- 0.35, and at 18 months 0.67 +/- 0.35. The probabilities for attaining 12 and 18 months of quality-adjusted survival were 30.1% and 19.1%, respectively. There were statistically significant differences in survival time and quality-adjusted life years according to all assessed baseline characteristics (ICU admission after elective surgery, emergency surgery, or medical admission; Simplified Acute Physiology Score 3; cancer extension; cancer status; previous surgery; previous chemotherapy; previous radiotherapy; performance status; and previous health related quality of life). Only the previous health-related quality of life and performance status were associated with the health-related quality of life during the 18-month follow-up. CONCLUSIONS: Long-term survival, health-related quality of life, and quality-adjusted life year expectancy of cancer patients admitted to the ICU are limited. Nevertheless, these clinical outcomes exhibit wide variability among patients and are associated with simple characteristics present at the time of ICU admission, which may help healthcare professionals estimate patients' prognoses. PMID- 26998656 TI - Statistically modelling the relationships between Type D personality and social support, health behaviors and symptom severity in chronic illness groups. AB - OBJECTIVE: The study aimed to develop a predictive model of how Type D personality influences health behaviours, social support and symptom severity and assess its generalisability to a range of chronic illnesses. DESIGN: Participants were classified as either healthy (n = 182) or having a chronic illness (n = 207). Participants completed an online survey measuring Type D and a range of health-related variables. Chronic illness participants were classified as having either a functional somatic syndrome (i.e. chronic fatigue syndrome or fibromyalgia), where the underlying pathological processes were unclear, or illnesses such as type 2 diabetes, osteoarthritis or rheumatoid arthritis, where the causes are well understood. MAIN OUTCOME MEASURES: Outcome measures were health behaviours, social support and both physical and psychological symptoms. RESULTS: The rate of Type D was higher in chronic illness participants (53%) than in healthy controls (39%). Negative affectivity (NA) and social inhibition (SI) both correlated with outcome measures, although NA was generally the stronger predictor. Using NA and SI as independent subscales led to superior prediction of health outcomes than using categorical or continuous representations. CONCLUSION: Findings suggest that the relationship between Type D and health outcomes may generalise across different chronic illnesses. PMID- 26998655 TI - Relationship Between Physical Activity and Suicidal Behaviors Among 65,182 Middle School Students. AB - BACKGROUND: The psychosocial benefits of participating in physical activity (PA) are well known; less is known about the relationship between suicidal behaviors and PA among adolescents, especially among middle school-aged youth. This study seeks to fill that gap by assessing the cross-sectional relationship between these variables. METHODS: A secondary analysis of the 2010 Tennessee Middle School Youth Risk Behavior Survey data was conducted among 65,182 middle school students. Items examined were PA, sports team engagement, physical education (PE) class, screen time, suicidal behaviors, drug/substance use, extreme weight control behaviors, weight status and weight misperceptions, and selected personal characteristics. Multiple logistic regression analysis was used to estimate the association between PA, sports team engagement, and PE class attendance on suicidal behaviors. RESULTS: Sports team engagement was significantly associated with suicidal thoughts, plans, and attempts even after controlling for other important variables. There was no relationship, however, between total PA or PE class attendance in univariate or multivariate models, respectively. CONCLUSIONS: Findings suggest that sports team engagement is associated with reduced risk for suicidal thoughts, plans, and attempts, whereas, no relationships were found for PA or PE class attendance. Asking adolescents questions about sports team engagement may help clinicians screen for risk of suicidal behaviors. PMID- 26998657 TI - The supervisor's toolkit: A framework for doctoral supervision in health professions education: AMEE Guide No. 104. AB - Doctoral studies represent a complex undertaking for students and supervisors. Some research describes the experience of students while there are volumes of advice for students considering a doctorate. Yet the terrain for supervisors is less well-trodden and the concept of a pedagogy of supervision is only really starting to emerge. Texts on the doctoral journey from the supervisor's perspective are uncommon and less yet has been written in the context of health professions education. The aim of this Guide, therefore, is to provide guidance for the supervisor's journey, drawing on our collective experience and such literature as there is. We explore the doctoral journey of students and their supervisors, highlighting what the implications are for supervisory practice. Recognising the doctorate as much more than merely conducting a research project, and seeing it as a shared educational endeavour is fundamental to understanding the doctoral journey - a journey that is complex and mutable, constantly shifting as the candidate moves from novice to expert, from dependence to growing autonomy. Our intention is to present this Guide as a toolkit for both the novice and the experienced supervisor as it, on the one hand, seeks to make the practice of supervision more transparent while on the other, challenges the reader to critically reflect on the supervisory space in which they currently reside. Our hope is that the Guide opens up opportunities for generative conversations about the practice of doctoral supervision in health professions education. PMID- 26998658 TI - Sorafenib for the treatment of multiple myeloma. AB - INTRODUCTION: Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM. AREAS COVERED: In this review, the authors discuss the rationale for the use of sorafenib in MM. They then summarize the clinical development of sorafenib in MM, from initial Phase I to Phase II studies. A systematic literature review of the trials was performed using PubMed. EXPERT OPINION: Preliminary data from phase I/II trials showed that sorafenib had a good safety profile but minimal anti-myeloma activity as a single agent in relapsed/refractory patients. Results of phase II trials, evaluating sorafenib combined with new drugs, such as bortezomib and lenalidomide are eagerly awaited. PMID- 26998660 TI - Effect of calcium on cell-wall degrading enzymes of Botrytis cinerea. AB - Effective anti-Botrytis strategies leading to reduce pesticides on strawberries are examined to provide the protection that is harmless to humans, higher animals and plants. Calcium treatments significantly inhibited the spore germination and mycelial growth of B. cinerea. The intracellular polygalacturonase and CMCase showed low activities in B. cinerea cultivated by medium containing calcium. On the other hand, calcium-stimulated beta-glucosidases production occurred. Our findings suggest that the calcium treatments keep CMCase activity low and cause low activities of cell-wall degrading enzymes of B. cinerea in the late stage of growth. PMID- 26998659 TI - Distinct neural substrates of affective and cognitive theory of mind impairment in semantic dementia. AB - Using structural MRI, we investigated the brain substrates of both affective and cognitive theory of mind (ToM) in 19 patients with semantic dementia. We also ran intrinsic connectivity analyses to identify the networks to which the substrates belong and whether they are functionally disturbed in semantic dementia. In line with previous studies, we observed a ToM impairment in patients with semantic dementia even when semantic memory was regressed out. Our results also highlighted different neural bases according to the nature (affective or cognitive) of the representations being inferred. The affective ToM deficit was associated with atrophy in the amygdala, suggesting the involvement of emotion processing deficits in this impairment. By contrast, cognitive ToM performances were correlated with the volume of medial prefrontal and parietal regions, as well as the right frontal operculum. Intrinsic connectivity analyses revealed decreased functional connectivity, mainly between midline cortical regions and temporal regions. They also showed that left medial temporal regions were functionally isolated, a further possible hindrance to normal social cognitive functioning in semantic dementia. Overall, this study addressed for the first time the neuroanatomical substrates of both cognitive and affective ToM disruption in semantic dementia, highlighting disturbed connectivity within the networks that sustain these abilities. PMID- 26998661 TI - Evaluation of Patient Tolerance and Small-Bowel Distention With a New Small-Bowel Distending Agent for Enterography. AB - OBJECTIVE: The objective of our study was to compare a flavored beverage containing a thickening agent for enterography with a low-Hounsfield-value barium suspension for side effects, taste, subjects' willingness to repeat the drinking protocol, and small-bowel distention. SUBJECTS AND METHODS: The following five drinking protocols were administered to 10 volunteers: 1000 mL of flavored beverage followed by 350 mL of water, 1500 mL of flavored beverage, 900 mL of low Hounsfield-value barium suspension followed by 450 mL of water, 1350 mL of low Hounsfield-value barium suspension followed by 150 mL of water, and 1500 mL of water. MR images were obtained 50 and 60 minutes after initiation of drinking. Subjects completed a questionnaire evaluating the side effects, the taste of the drink, and their willingness to repeat the drinking protocol. Reviewers assigned scores evaluating small-bowel distention and ranked the examinations in order of preference. RESULTS: There was no significant difference in nausea or vomiting among the protocols (p = 0.20 and 0.42, respectively), but larger volumes of flavored beverage and low-Hounsfield-value barium suspension resulted in more cramping and diarrhea (p = 0.001 and 0.002, respectively). The taste of the low Hounsfield-value barium suspension was rated the worst (p < 0.0001). The subjects' willingness to repeat the drinking protocol was highest for the 1000 mL of flavored beverage or water alone (p < 0.05). There were no significant differences in subjective small-bowel distention except that water was rated the worst by two of the three readers (p < 0.02). There was no significant difference in the diameter of the most dis-tended small bowel for any segment or reader (p > 0.23). CONCLUSION: A flavored beverage containing a thickening agent has a similar side effect profile and results in equivalent small-bowel distention compared with a low-Hounsfield-value barium suspension, but subjects rate taste and their willingness to repeat the drinking protocol higher for this new agent. PMID- 26998663 TI - Prenatal exposure to cigarette smoke enhances oxidative stress in astrocytes of neonatal rat. AB - Oxidative stress is involved in the pathogenesis of smoking-related disease. Protection of astrocytes from oxidative insult appears essential to maintain brain function. In this study, we have investigated the effect of gestational cigarette exposure on astrocyte survival. Pregnant female were randomly allocated to the control group or to the cigarette smoke group in which they were placed in an exposure chamber and inhale three cigarettes smoke twice a day for a period of 20 days. The control group was kept in the exposure chamber for the same duration, but without exposure to cigarette smoke. Newborn rats from both groups were weighed 24 h after birth and then cerebral hemispheres were collected for astrocyte culture. Incubation of astrocytes isolated from animals exposed to cigarette smoke with 300 MUM H2O2 for 1 h induced a significant decrease of the proportion of surviving cells compared to cells isolated form control animals. We have observed that H2O2-treated astroglial cells derived from cigarette smoke exposure showed more reduced superoxide dismutase and catalase activities than H2O2-treated astroglial cells from control animals. In conclusion, this study indicates that astroglial cells derived from newborn rats exposed in utero to cigarette smoke are more vulnerable to oxidative assault than cultured astrocytes obtained from control animals. These results point out the existence of excitotoxic lesions in newborn exposed in utero to cigarette smoke and suggest that despite their high antioxidative activities, astrocytes cannot survive and protect neurons under massive oxidative stress. PMID- 26998665 TI - Comparison of National Board of Chiropractic Examiners part I examination scores between tutors and tutees at a chiropractic college. AB - OBJECTIVE: This study compared National Board of Chiropractic Examiners part I test scores between students who did and did not serve as tutors on the subject matter. METHODS: Students who had a prior grade point average of 3.45 or above on a 4.0 scale just before taking part I of the board exams were eligible to participate. A 2-sample t-test was used to ascertain the difference in the mean scores on part I between the tutor group (n = 28) and nontutor (n = 29) group. RESULTS: Scores were higher in all subjects for the tutor group compared to the nontutor group and the differences were statistically significant (p < .01) with large effect sizes. CONCLUSION: The tutors in this study performed better on part I of the board examination compared to nontutors, suggesting that tutoring results in an academic benefit for tutors themselves. PMID- 26998664 TI - Immunology knowledge as one of the basic sciences that forms the foundations to developing sound clinicians. AB - OBJECTIVE: The aim of this study was to (1) generate a valid questionnaire to determine immunology knowledge, (2) compare immunology knowledge across 3 different cohorts of chiropractic students that had already studied immunology, (3) examine the attitudes of chiropractic students to the study of immunology, and (4) examine whether students' attitudes affected their knowledge levels. METHODS: Factor analysis was used to refine an immunology knowledge and perceptions questionnaire that was generated by a group of experts that was then completed by 90 students. Immunology knowledge level of each of the cohorts was compared using a 1-way analysis of variance. Kappa statistics were used to measure agreement between 2 statements, and logistic regression was used to determine whether students' attitudes were associated with their knowledge levels. RESULTS: There was a significant difference in the immunology knowledge levels across the 3 year groups (F[2, 87] = 4.78, p = .011). Fifth-year students (n = 26) demonstrated 25% less immunology knowledge than third-year students (n = 35; p = .005). Of 90 students, 64 agreed that immunology knowledge was important to chiropractors, and 53 agreed that immunology knowledge was important for the average person. No relationship existed between their value of immunology knowledge and their score on the multiple-choice questions. CONCLUSION: Third year students' immunology knowledge was significantly higher than that of the fifth-year students. Students value immunology knowledge, but this does not translate to retention of this knowledge. The validated questionnaire is a useful tool for assessing immunology knowledge retention for undergraduate students. PMID- 26998662 TI - Progress and challenges associated with the development of ricin toxin subunit vaccines. AB - The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine, including the completion of two Phase I clinical trials with two different recombinant A subunit (RTA)-based vaccines: RiVaxTM and RVEcTM adsorbed to aluminum salt adjuvant, as well as a non-human primate study demonstrating that parenteral immunization with RiVax elicits a serum antibody response that was sufficient to protect against a lethal dose aerosolized ricin exposure. One of the major obstacles moving forward is assessing vaccine efficacy in humans, when neither ricin-specific serum IgG endpoint titers nor toxin neutralizing antibody levels are accepted as definitive predictors of protective immunity. In this review we summarize ongoing efforts to leverage recent advances in our understanding of RTA-antibody interactions at the structural level to develop novel assays to predict vaccine efficacy in humans. PMID- 26998666 TI - Is It Time for a Nonionizing Radiation Technique for Biopsy of Anterior Mediastinal Masses? PMID- 26998667 TI - Submicroscopic chromosomal abnormalities in fetuses with increased nuchal translucency and normal karyotype. AB - OBJECTIVE: To investigate the submicroscopic chromosomal abnormalities in fetuses with increased nuchal translucency (NT) and normal karyotype. METHODS: Total of 296 fetuses with increased NT (>=3.0 mm) were tested by conventional karyotyping. When cytogenetic analysis showed normal chromosome, the pregnancies were then consulted for array-comparative genomic hybridization (CGH) analysis and received subsequent morphology scan between 20 and 24 weeks gestation. Submicroscopic chromosomal abnormalities were assessed and compared between the fetuses with and without structural defects. RESULTS: Chromosomal abnormality was identified in 19.9% (59/296) fetuses. Two hundred and twenty samples were tested by array CGH. Submicroscopic chromosomal abnormalities were detected in 9.1% (20/220) fetuses. For the fetuses with abnormal morphology scan, the detection rate of submicroscopic chromosomal abnormalities was higher than those with normal morphology scan (26.9% versus 6.7%, p < 0.05). CONCLUSIONS: Submicroscopic chromosomal abnormalities should be accessed when the fetus was found to be with increased NT and normal karyotype, especially when the structural defects were found at second or third trimester. PMID- 26998668 TI - Evaluation of layered and mixed passive treatment systems for acid mine drainage. AB - Laboratory column tests for passive treatment systems for mine drainage from a waste rock storage area were conducted to evaluate suitable reactive mixture, system configuration, effects of influent water chemistry, and required residence time. Five columns containing straw, chicken manure, mushroom compost, and limestone (LS), in either layered or mixed configurations, were set up to simulate the treatment system. The results showed that all of the five columns removed metals of concern (i.e. Al, Cd, Co, Cu, Fe, Ni, and Zn) with a residence time of 15 h and greater. Reaction mechanisms responsible for the removal of metals may include sulfate reduction and subsequent sulfide precipitation, precipitation of secondary carbonates and hydroxides, co-precipitation, and sorption on organic substrates and secondary precipitates. The results suggest that the mixed systems containing organic materials and LS perform better than the layered systems, sequentially treated by organic and LS layers, due to the enhanced pH adjustment, which is beneficial to bacterial activity and precipitation of secondary minerals. The column tests provide a basis for the design of a field-scale passive treatment system, such as a reducing and alkalinity producing system or a permeable reactive barrier. PMID- 26998669 TI - Catalytic conversion of methanol/ethanol to isobutanol--a highly selective route to an advanced biofuel. AB - Catalysts based on ruthenium diphosphine complexes convert methanol/ethanol mixtures to the advanced biofuel isobutanol, with extremely high selectivity (>99%) at good (>75%) conversion via a Guerbet-type mechanism. PMID- 26998670 TI - Selective Oxidation of an Active Intramolecular Amine/Borane Frustrated Lewis Pair with Dioxygen. AB - Oxidation reactions are rarely encountered in frustrated Lewis pair (FLP) chemistry. We describe the selective reaction of an amine/borane FLP with molecular oxygen. The trimethylene-bridged amine/borane frustrated Lewis pair was prepared by hydroboration of N-allyl-tetramethylpiperidine with Piers' borane [HB(C6F5)2]. The intramolecular N/B system undergoes a variety of typical FLP reactions. It is a very active hydrogen splitting reagent at ambient conditions. Its reaction with dioxygen takes place rapidly at ambient conditions to give a tetrahydroisoxazolium/borate salt. A possible pathway of its formation is proposed and supported by DFT calculations. PMID- 26998671 TI - Tracking of STAT3 signaling for anticancer drug-discovery based on localized surface plasmon resonance. AB - Signal transducer and activator of transcription 3 (STAT3) protein signaling is crucial for the survival, invasion, and growth of human cancer cells; thus, STAT3 protein is an ideal target for a new drug screening system. Herein, we developed a label-free sensor for anticancer drug-discovery based on the localized surface plasmon resonance (LSPR) shift response by tracking of STAT3 signaling including phosphorylation and dimerization. This enables ultrasensitive monitoring of the molecular interactions that occur on the surface of single gold nanoparticles. The red shift of the LSPR lambdamax was observed as 3.46 nm and 9.00 nm, respectively, indicating phosphorylation and dimerization of the STAT3 signaling pathway. In screening of anticancer candidates, the system worked well in the presence of STA-21 which inhibits STAT3 dimerization. The LSPR lambdamax shift in the inhibition condition is three times lower than that in the absence of an inhibitor. Interestingly, the system reveals high specificity, reproducibility and compatibility with real samples (MCF-7 cell line). Therefore, these results demonstrated that this system has strong potential to be an accurate and effective sensor for tracking of signaling pathways and drug screening of anticancer candidates for anticancer therapy. PMID- 26998672 TI - Design and Preparation of MnO2/CeO2-MnO2 Double-Shelled Binary Oxide Hollow Spheres and Their Application in CO Oxidation. AB - Herein, we designed an extremely facile method to prepare well-defined MnO2@CeO2 MnO2 ball-in-ball binary oxide hollow spheres by employing carbon spheres (CSs) as sacrificial templates. The synthesis process involves a novel self-assembled approach to prepare core-shell CSs@CeO2 precursor, which would directly react with KMnO4 aqueous solution to form yolk-shell CSs@MnO2/CeO2-MnO2 precursor in the following step. Well-dispersed Ce-Mn binary oxide with double-shelled hollow sphere structure could be achieved after annealing the precursor in air. The evolution process and formation mechanism of this novel structure were thoroughly studied in this paper. Especially the as-prepared double-shell MnO2/CeO2-MnO2 hollow spheres exhibited enhanced catalytic activity for CO oxidation compared with the pure MnO2 hollow spheres and pure CeO2 hollow spheres. We believe the high surface area, hierarchical porous structures, and strong synergistic interaction between CeO2 and MnO2 contribute to the excellent catalytic activity. Most importantly, this method could be extended to prepare other transition metal oxides. As an example, triple-shelled Co-Mn composite hollow spheres assembled by ultrathin nanoplates were successfully prepared. PMID- 26998674 TI - Tungsten Bronze Barium Neodymium Titanate (Ba(6-3n)Nd(8+2n)Ti(18)O(54)): An Intrinsic Nanostructured Material and Its Defect Distribution. AB - We investigated the structure of the tungsten bronze barium neodymium titanates Ba(6-3n)Nd(8+2n)Ti(18)O(54), which are exploited as microwave dielectric ceramics. They form a complex nanostructure, which resembles a nanofilm with stacking layers of ~12 A thickness. The synthesized samples of Ba(6 3n)Nd(8+2n)Ti(18)O(54) (n = 0, 0.3, 0.4, 0.5) are characterized by pentagonal and tetragonal columns, where the A cations are distributed in three symmetrically inequivalent sites. Synchrotron X-ray diffraction and electron energy loss spectroscopy allowed for quantitative analysis of the site occupancy, which determines the defect distribution. This is corroborated by density functional theory calculations. Pentagonal columns are dominated by Ba, and tetragonal columns are dominated by Nd, although specific Nd sites exhibit significant concentrations of Ba. The data indicated significant elongation of the Ba columns in the pentagonal positions and of the Nd columns in tetragonal positions involving a zigzag arrangement of atoms along the b lattice direction. We found that the preferred Ba substitution occurs at Nd[3]/[4] followed by Nd[2] and Nd[1]/[5] sites, which is significantly different to that proposed in earlier studies. Our results on the Ba(6-3n)Nd(8+2n)Ti(18)O(54) "perovskite" superstructure and its defect distribution are particularly valuable in those applications where the optimization of material properties of oxides is imperative; these include not only microwave ceramics but also thermoelectric materials, where the nanostructure and the distribution of the dopants will reduce the thermal conductivity. PMID- 26998675 TI - [Metabolic monitoring on small and medium sized dairy farms in Emsland, Germany]. AB - OBJECTIVE: The aim of this study was to evaluate metabolic analyses on small dairy farms regarding indications, realization, and results over 5 years. MATERIAL AND METHODS: In 793 serum samples (122 submissions from 53 farms) originating from cows of different lactation stages and from heifers, the parameters free fatty acids (FFA), beta-hydroxybutyrate (BHB), cholesterol, urea, creatinine, glucose, total protein, albumin, bilirubin, liver enzymes, creatine kinase (CK), beta-carotene, electrolytes and trace elements were analyzed. RESULTS: In 20% of cases, investigations were initiated to control for the metabolic status. Further reasons for laboratory diagnostics were consistent with the culling causes. FFA with 56.7% displayed the most frequent deviations from the normal range during the lactation ante partum. At 8 weeks post partum (p. p.) it fell to 36-38% and later to < 11%. The BHB deviations from the normal range exceeded 68% throughout the whole lactation. During the middle and late lactation, 40-50% of the measured urea concentrations were above the upper reference limit. Hypocalcemia occurred during the first week p. p. to 13.2% and hypophosphatemia to 6.6%. For CK, deviations from the reference value of 60.4 90.0% were determined. Selenium and copper deficiencies were present in approximately 15% of cases. Heifers more frequently displayed a copper deficiency (21.3%) than cows. beta-carotene deficiency was measured ante partum at 50% and p. p. at 47.1-77.8%. Adverse deviations increased between 2006 and 2011 for FFS, urea, beta-carotene, and selenium in correlation with a reduction in the milk price between 2009 and 2010. Deviations from the normal range for BHB, CK, cholesterol, calcium, and inorganic phosphate remained constant. On 80% of the farms, the metabolic status improved during the investigation period. CONCLUSION: Even on smaller farms, peripartal metabolic screenings enable early discovery of causes of the most common culling reasons and provide options for corrective action. PMID- 26998673 TI - Fluorescence Resonance Energy Transfer Characterization of DNA Wrapping in Closed and Open Escherichia coli RNA Polymerase-lambdaP(R) Promoter Complexes. AB - Initial recognition of promoter DNA by RNA polymerase (RNAP) is proposed to trigger a series of conformational changes beginning with bending and wrapping of the 40-50 bp of DNA immediately upstream of the -35 region. Kinetic studies demonstrated that the presence of upstream DNA facilitates bending and entry of the downstream duplex (to +20) into the active site cleft to form an advanced closed complex (CC), prior to melting of ~13 bp (-11 to +2), including the transcription start site (+1). Atomic force microscopy and footprinting revealed that the stable open complex (OC) is also highly wrapped (-60 to +20). To test the proposed bent-wrapped model of duplex DNA in an advanced RNAP-lambdaP(R) CC and compare wrapping in the CC and OC, we use fluorescence resonance energy transfer (FRET) between cyanine dyes at far-upstream (-100) and downstream (+14) positions of promoter DNA. Similarly large intrinsic FRET efficiencies are observed for the CC (0.30 +/- 0.07) and the OC (0.32 +/- 0.11) for both probe orientations. Fluorescence enhancements at +14 are observed in the single-dye labeled CC and OC. These results demonstrate that upstream DNA is extensively wrapped and the start site region is bent into the cleft in the advanced CC, reducing the distance between positions -100 and +14 on promoter DNA from >300 to <100 A. The proximity of upstream DNA to the downstream cleft in the advanced CC is consistent with the proposed mechanism for facilitation of OC formation by upstream DNA. PMID- 26998676 TI - Impact of Early Blood Transfusion After Kidney Transplantation on the Incidence of Donor-Specific Anti-HLA Antibodies. AB - Little is known about the impact of posttransplant blood transfusion on the sensitization of anti-HLA antibodies and the formation of donor-specific antibodies (DSAs). The aims of our study were to determine the 1-year incidence of DSAs (assessed using a solid-phase assay) and antibody-mediated rejection (AMR) in kidney transplant patients who had or had not received a blood transfusion during the first year after transplantation. Included were 390 non HLA-sensitized patients who had received an ABO-compatible kidney transplant and had not previously or simultaneously received a nonkidney transplant. Overall, 64% of patients received a red blood cell transfusion within the first year after transplantation, most within the first month. The overall 1-year incidence of DSAs was significantly higher in patients that had undergone transfusion (7.2% vs. 0.7% in patients with no transfusion, p < 0.0001). AMR occurred more often in the transfusion group (n = 15, 6%) compared with the nontransfusion group (n = 2, 1.4%; p = 0.04). Blood transfusion was an independent predictive factor for de novo DSA formation but not for AMR. Patients who had a transfusion and developed DSAs were more often treated with cyclosporin A (n = 10, 55.5%) rather than tacrolimus (n = 45, 19.4%; p = 0.0001). In conclusion, early posttransplant blood transfusion may increase immunological risk, especially in underimmunosuppressed patients. PMID- 26998678 TI - Year in review 2015: Lung cancer, pleural diseases, respiratory infections, bronchiectasis and tuberculosis, bronchoscopic intervention and imaging. PMID- 26998677 TI - Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity. AB - BACKGROUND: The proliferation of clonal cytotoxic T-cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). METHODS: The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP), CML-CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid-blast phase were analyzed. RESULTS: Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib-treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML-CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression-free and overall survival rates were significantly longer in patients with CML-CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. CONCLUSIONS: Overall, lymphocytosis occurred and persisted in many dasatinib-treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016;122:1398-1407. (c) 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. PMID- 26998679 TI - Porous Covalent Triazine Polymer as a Potential Nanocargo for Cancer Therapy and Imaging. AB - A microporous covalent triazine polymer (CTP) network with a high surface area was synthesized via the Friedel-Crafts reaction and employed as a potential transport system for drug delivery and controlled release. The CTP was transformed to the nanoscale region by intense ultrasonication followed by filtration to yield nanoscale CTP (NCTP). This product showed excellent dispersibility in physiological solution while maintaining its chemical structure and porosity. An anticancer drug, doxorubicin (DOX), was loaded onto the NCTP through hydrophobic and pi-pi interactions, and its release was controlled at pH 4.8 and 7.4. The NCTP showed no toxicity toward cancer or normal cells, but the NCTP-DOX complex showed high efficacy against both types of cells in vitro. In vitro cell imaging revealed that NCTP is a potential material for bioimaging. The potency of NCTP on cellular senescence was confirmed by the expression of senescence associated marker proteins p53 and p21. These results suggest that NCTP can be used as a new platform for drug delivery and imaging with potential applications in diagnosis and therapy. PMID- 26998680 TI - Physiochemical Properties of Aluminum Adjuvants Elicit Differing Reorganization of Phospholipid Domains in Model Membranes. AB - Most vaccines contain aluminum adjuvants; however, their exact mechanism of action remains unclear. A novel mechanism by Shi and colleagues proposes aluminum adjuvants may enhance immune activation by binding and reorganizing lipids that are key components of lipid rafts. To better understand the specificity of interaction between aluminum adjuvants and the cell membrane lipids, we present a biophysical study of lipid domain clustering in simple model phospholipid monolayers containing dipalmitoyl-phosphatidylcholine (DPPC) and dioleoyl phosphatidylcholine (DOPC) exposed to two aluminum adjuvants, Alhydrogel and Adju Phos. Surface pressure measurements and fluorescence microscopy images verified aluminum adjuvant-induced increase in lipid domain size, even in the key lipid raft components. Additionally, adjuvant induced lipid clustering differed based on the physicochemical properties of the adjuvants. Alhydrogel appeared to reduce monolayer compressibility and insert into the monolayer, while Adju-Phos induced more significant changes in domain size, without compromising the integrity of the monolayer. The Alhydrogel and Adju-Phos-mediated reorganization of phospholipid domains reported here supports the new mechanistic paradigm proposed by Shi and co-workers, and further suggests that lipid clustering is induced even in simple phospholipid membranes. The results present the basis for future exploration into lipid-mediated mechanisms of action for adjuvants. PMID- 26998681 TI - Novel topical treatments for psoriasis: of interest or irrelevant? PMID- 26998682 TI - Innervation of dystrophic muscle after muscle stem cell therapy. AB - INTRODUCTION: Duchenne muscular dystrophy (DMD) is caused by loss of the structural protein, dystrophin, resulting in muscle fragility. Muscle stem cell (MuSC) transplantation is a potential therapy for DMD. It is unknown whether donor-derived muscle fibers are structurally innervated. METHODS: Green fluorescent protein (GFP)-expressing MuSCs were transplanted into the tibials anterior of adult dystrophic mdx/mTR mice. Three weeks later the neuromuscular junction was labeled by immunohistochemistry. RESULTS: The percent overlap between pre- and postsynaptic immunolabeling was greater in donor-derived GFP(+) myofibers, and fewer GFP(+) myofibers were identified as denervated compared with control GFP(-) fibers (P = 0.001 and 0.03). GFP(+) fibers also demonstrated acetylcholine receptor fragmentation and expanded endplate area, indicators of muscle reinnervation (P = 0.008 and 0.033). CONCLUSION: It is unclear whether GFP(+) fibers are a result of de novo synthesis or fusion with damaged endogenous fibers. Either way, donor-derived fibers demonstrate clear histological innervation. Muscle Nerve 54: 763-768, 2016. PMID- 26998683 TI - Exercise-based cardiac rehabilitation for adults after heart valve surgery. AB - BACKGROUND: Exercise-based cardiac rehabilitation may benefit heart valve surgery patients. We conducted a systematic review to assess the evidence for the use of exercise-based intervention programmes following heart valve surgery. OBJECTIVES: To assess the benefits and harms of exercise-based cardiac rehabilitation compared with no exercise training intervention, or treatment as usual, in adults following heart valve surgery. We considered programmes including exercise training with or without another intervention (such as a psycho-educational component). SEARCH METHODS: We searched: the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS (Bireme); and Conference Proceedings Citation Index-S (CPCI-S) on Web of Science (Thomson Reuters) on 23 March 2015. We handsearched Web of Science, bibliographies of systematic reviews and trial registers (ClinicalTrials.gov, Controlled-trials.com, and The World Health Organization International Clinical Trials Registry Platform). SELECTION CRITERIA: We included randomised clinical trials that investigated exercise-based interventions compared with no exercise intervention control. The trial participants comprised adults aged 18 years or older who had undergone heart valve surgery for heart valve disease (from any cause) and received either heart valve replacement, or heart valve repair. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. We assessed the risk of systematic errors ('bias') by evaluation of bias risk domains. Clinical and statistical heterogeneity were assessed. Meta-analyses were undertaken using both fixed-effect and random-effects models. We used the GRADE approach to assess the quality of evidence. We sought to assess the risk of random errors with trial sequential analysis. MAIN RESULTS: We included two trials from 1987 and 2004 with a total 148 participants who have had heart valve surgery. Both trials had a high risk of bias.There was insufficient evidence at 3 to 6 months follow-up to judge the effect of exercise-based cardiac rehabilitation compared to no exercise on mortality (RR 4.46 (95% confidence interval (CI) 0.22 to 90.78); participants = 104; studies = 1; quality of evidence: very low) and on serious adverse events (RR 1.15 (95% CI 0.37 to 3.62); participants = 148; studies = 2; quality of evidence: very low). Included trials did not report on health-related quality of life (HRQoL), and the secondary outcomes of New York Heart Association class, left ventricular ejection fraction and cost. We did find that, compared with control (no exercise), exercise-based rehabilitation may increase exercise capacity (SMD -0.47, 95% CI -0.81 to -0.13; participants = 140; studies = 2, quality of evidence: moderate). There was insufficient evidence at 12 months follow-up for the return to work outcome (RR 0.55 (95% CI 0.19 to 1.56); participants = 44; studies = 1; quality of evidence: low). Due to limited information, trial sequential analysis could not be performed as planned. AUTHORS' CONCLUSIONS: Our findings suggest that exercise based rehabilitation for adults after heart valve surgery, compared with no exercise, may improve exercise capacity. Due to a lack of evidence, we cannot evaluate the impact on other outcomes. Further high-quality randomised clinical trials are needed in order to assess the impact of exercise-based rehabilitation on patient-relevant outcomes, including mortality and quality of life. PMID- 26998686 TI - A Light/Ketone/Copper System for Carboxylation of Allylic C-H Bonds of Alkenes with CO2. AB - A photo-induced carboxylation reaction of allylic C-H bonds of simple alkenes with CO2 is prompted by means of a ketone and a copper complex. The unique carboxylation reaction proceeds through a sequence of an endergonic photoreaction of ketones with alkenes forming homoallyl alcohol intermediates and a thermal copper-catalyzed allyl transfer reaction from the homoallyl alcohols to CO2 through C-C bond cleavage. PMID- 26998685 TI - High circulating oestrone and low testosterone correlate with adverse clinical outcomes in men with advanced liver disease. AB - BACKGROUND & AIMS: Circulating testosterone is usually reduced in men with cirrhosis, but there has not been a comprehensive analysis of androgen status or circulating oestrogens. Little is known about associations between circulating sex steroids with aspects of health in this population. METHODS: We report data from men with cirrhosis and low serum testosterone (<12 nmol/L or calculated free testosterone <230 pmol/L). Comprehensive circulating sex steroid profiles were measured by liquid chromatography-mass spectrometry and compared with age-matched controls. Relationships between sex hormone levels, severity of liver disease, biochemistry and clinical outcomes were assessed. RESULTS: Serum oestrone and oestradiol were significantly elevated in men with cirrhosis compared with controls (median, 869.1 pmol/L vs. 133.8 pmol/L and 166.7 pmol/L vs. 84.6 pmol/L respectively). Serum oestrone correlated with MELD score (correlation +0.306, P < 0.001) and inversely correlated with serum sodium (correlation -0.208, P = 0.004) and haemoglobin (correlation -0.177, P = 0.012). No such correlations were observed for oestradiol. Serum testosterone levels inversely correlated with MELD score (correlation -0.294, P < 0.001) and positively with handgrip strength (correlation +0.242, P < 0.001), physical activity (correlation +0.276, P = 0.012), haemoglobin (correlation +0.282, P < 0.001) and serum sodium (+0.344, P < 0.001). Dihydrotestosterone inversely correlated with MELD score (correlation 0.225, P = 0.002) and shared similar significant relationships to testosterone. CONCLUSION: Low serum androgens and elevated serum oestrone (but not oestradiol) are associated with higher MELD and individual adverse health outcomes in cirrhotic cohort of men selected for low testosterone. Serum oestrone may be a novel marker of ill health in this population. Whether low androgens are markers or mediators of ill health requires further investigation. PMID- 26998684 TI - Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats. AB - Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 MUg 17beta-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as shown in (a). Furthermore, the alterations in local spinal blood flow could be significantly alleviated with low dose estrogen therapy. This therapy led to the preservation of the structural integrity of the spinal cord (b), which in turn led to the improved functional recovery as shown (c). PMID- 26998687 TI - Anti-Aspergillus immunoglobulin-G testing in serum of hematopoietic stem cell transplant recipients. AB - BACKGROUND: Pulmonary invasive aspergillosis (IA) is a major clinical problem in patients undergoing allogeneic hematopoietic stem cell transplantation (allo HSCT). Acquisition of IA during allo-HSCT by inhalation of spores is the rationale for the widespread use of air filtration systems. Recent data suggest that activation of fungal growth in already colonized patients is a relevant factor, and a recent study found a positive correlation of serum immunoglobulin responses against purified recombinant Aspergillus fumigatus proteins before allo HSCT with the incidence of IA after allo-HSCT. METHODS: To investigate the clinical utility of this approach, we performed a prospective study. We used a commercially available and standardized assay for detection of anti-Aspergillus immunoglobulin-G (aA-IgG) in serum (Platelia(TM) Aspergillus IgG) that has previously demonstrated high sensitivity and specificity. RESULTS: In a cohort of 104 allo-HSCT recipients, we measured aA-IgG and Aspergillus antigen serum levels before allo-HSCT, and weekly during hospital stay. Overall prevalence of possible, probable, and proven IA during hospital stay was 10%, 6%, and 0%. We found no correlation between aA-IgG levels before allo-HSCT, or after allo-HSCT, and the prevalence of IA during hospital stay. Furthermore, median aA-IgG levels did not differ between patients with history of probable or proven IA, as compared to patients without history of IA. CONCLUSIONS: Taken together, our data argue against the clinical utility of measuring aA-IgG levels for diagnosis or prediction of IA in patients undergoing allo-HSCT. PMID- 26998688 TI - Reversible Disassembly-Assembly of Octa Acid-Guest Capsule in Water Triggered by a Photochromic Process. AB - Octa acid (OA), a calixarene-based cavitand, forms a 1:2 capsular assembly with neutral 1,3,3-trimethyl-6'-nitrospiro[2H-1]benzopyran-2,2'-indoline and 1:1 cavitandplex with its open zwitterionic merocyanine form. Photochromic interconversion between the spiropyran and merocyanine leads to unprecedented reversible capsular disassembly and assembly. OA provides stability to the merocyanine in both the ground and excited states. The photochemically controlled disassembly and assembly process established here points toward the opportunity of using the OA capsule in delivering small molecules at the desired locations. PMID- 26998689 TI - Hidden genetic variation in the germline genome of Tetrahymena thermophila. AB - Genome architecture varies greatly among eukaryotes. This diversity may profoundly affect the origin and maintenance of genetic variation within a population. Ciliates are microbial eukaryotes with unusual genome features, such as the separation of germline and somatic genomes within a single cell and amitotic division. These features have previously been proposed to increase the rate of molecular evolution in these species. Here, we assessed the fitness effects of genetic variation in the two genomes of natural isolates of the ciliate Tetrahymena thermophila. We find more extensive genetic variation in fitness in the transcriptionally silent germline genome than in the expressed somatic genome. Surprisingly, this variation is not primarily deleterious, but has both beneficial and deleterious effects. We conclude that Tetrahymena genome architecture allows for the maintenance of genetic variation that would otherwise be eliminated by selection. We consider the effect of selection on the two genomes and the impacts of reproductive strategies and the mechanism of sex determination on the structure of this variation. PMID- 26998690 TI - A role for the bacterial GATC methylome in antibiotic stress survival. AB - Antibiotic resistance is an increasingly serious public health threat. Understanding pathways allowing bacteria to survive antibiotic stress may unveil new therapeutic targets. We explore the role of the bacterial epigenome in antibiotic stress survival using classical genetic tools and single-molecule real time sequencing to characterize genomic methylation kinetics. We find that Escherichia coli survival under antibiotic pressure is severely compromised without adenine methylation at GATC sites. Although the adenine methylome remains stable during drug stress, without GATC methylation, methyl-dependent mismatch repair (MMR) is deleterious and, fueled by the drug-induced error-prone polymerase Pol IV, overwhelms cells with toxic DNA breaks. In multiple E. coli strains, including pathogenic and drug-resistant clinical isolates, DNA adenine methyltransferase deficiency potentiates antibiotics from the beta-lactam and quinolone classes. This work indicates that the GATC methylome provides structural support for bacterial survival during antibiotic stress and suggests targeting bacterial DNA methylation as a viable approach to enhancing antibiotic activity. PMID- 26998691 TI - Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population. AB - Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortium and population-based resources (total n > 38,000), we find genome-wide genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both LD score correlation and de novo variant analysis, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in diagnosis with an ASD or other neuropsychiatric disorder. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology. PMID- 26998693 TI - Epidemiology and radiological geometric assessment of pituitary macroadenomas: population-based study. AB - CONTEXT: Pituitary adenomas are relatively common tumours with diverse clinical features. Epidemiological data are important to help quantify health burden. OBJECTIVE: To provide in-depth epidemiological data on macroadenomas and radiologically characterize macroadenomas. DESIGN: Population-based retrospective analysis, Prevalence as at 2014; Incidence based on data from 2000 to 2014, Retrospective analysis of baseline MRI. SETTING: The Maltese islands. PATIENTS: 173/136 patients with macroadenomas for prevalence/incidence estimates respectively, 122 baseline MRI for radiological characterization. MAIN OUTCOME MEASURES: Prevalence rates, Standardized Incidence rates (SIR), MRI findings. RESULTS: The prevalence for macroadenomas was 40.67/100 000 people and the SIR was 1.90/100 000/year. Giant pituitary adenomas (>40 mm) constituted 4.8% of the whole cohort of PAs and the SIR was 0.18/100 000/year. Giant prolactinomas constituted 4.7% of all the prolactinomas and the SIR was 0.07/100 000/year, while giant NFPA constituted 6.0% of all NFPA and the SIR was 0.12/100 000/year. There was a statistically significant difference in the degree of suprasellar extension (P < 0.001) and infrasellar extension (P = 0.028) between the different macroadenoma subtypes and in the vertical extension indices (median vertical extension index NFPA 3.0 mm; PRLoma -7.7 mm; GH-secreting PA -1.7 mm; P < 0.001). Pituitary macroadenomas with cavernous sinus invasion were statistically significantly larger than those without cavernous sinus invasion (P < 0.001). NFPA had predominantly a superior extension into the cavernous sinus (63.6%) compared to the functional PAs which had predominantly an inferior extension into the cavernous sinus (59.1%) (P = 0.032). CONCLUSIONS: The various macroadenoma subtypes' epidemiological data are presented and differences between growth patterns among the various subtypes are highlighted. PMID- 26998695 TI - Vocational Functioning in Schizophrenia Spectrum Disorders: Does Apathy Matter? AB - While the influence of negative symptoms on vocational outcome is well documented, the specific contribution of apathy is less explored. The current study examined the influence of apathy on vocational outcome. A total of 148 participants were included in a vocational rehabilitation study, offering cognitive remediation (CR) or cognitive behavior therapy (CBT) to address work related issues. Clinical and functional measures were assessed on inclusion and at posttreatment after approximately 10 months. The level of apathy was not related to the acquisition of work, but higher levels of apathy predicted fewer hours worked per week during the study. Previous employment predicted future employment, and higher education predicted more hours worked and higher score on the Work Behavior Inventory. The results did not differ across interventions. Thus, despite apathy, people with schizophrenia were able to work when the barriers to employment were addressed and adequate support was given. PMID- 26998696 TI - Interpersonal Subtypes of Anxiety Disorder Patients: Relationship to Assessment and Treatment Variables. AB - We attempted to replicate earlier findings of interpersonal subtypes in patients with anxiety disorder (Psychotherapy. 2011;48:304-310) and examine whether these subtypes are characterized by different types of pathology and respond differently to treatment. Interpersonal problems were measured by the Inventory of Interpersonal Problems (Inventory of Interpersonal Problems Manual. San Antonio, TX: Psychological Cooperation; 2000) in a sample of 31 patients with anxiety disorder. Results demonstrated the existence of 4 interpersonal subtypes. The subtypes did not differ in severity of anxiety and global levels of symptoms at pretreatment or in Reliable Change Index of anxiety symptoms over the course of treatment. However, they were significantly different in terms of overall interpersonal problems (p = 0.004). Regarding treatment variables, half of the patients in the nonassertive cluster discontinued treatment prematurely. The number of psychotherapy sessions attended was significantly different across the 4 clusters (p = 0.04), with socially avoidant patients attending significantly greater number of sessions. PMID- 26998692 TI - Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. AB - Type 1 (T1D) and type 2 (T2D) diabetes share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, whereas beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alters the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role of beta cell fragility in genetic predisposition to diabetes. PMID- 26998694 TI - Anxiety and Shame as Risk Factors for Depression, Suicidality, and Functional Impairment in Body Dysmorphic Disorder and Obsessive Compulsive Disorder. AB - Body dysmorphic disorder (BDD) and obsessive compulsive disorder (OCD) are associated with elevated depression, suicidality, functional impairment, and days housebound, yet little research has identified risk factors for these outcomes. Using path analysis, the present study examined anxiety and shame as risk factors for these outcomes across Internet-recruited self-report groups (BDD [n = 114], OCD [n = 114], and healthy control [HC; n = 133]). Paths from anxiety and shame to outcomes were similar and mostly significant across BDD and OCD, compared to non-significant paths for HCs, with one exception: the path from shame to depression was significant in the BDD group (b = 0.32) but non-significant in the OCD group (b = 0.07). Findings underscore similarities in BDD and OCD, supporting their reclassification into the same Obsessive Compulsive Related Disorders category. Results emphasize the importance of targeting shame, in addition to anxiety, in treatments for BDD and OCD. PMID- 26998697 TI - Effects of 3,4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting. AB - 3,4-Methylenedioxymethamphetamine (MDMA) administered as an adjunct to talk therapy influences patient speech content and increases improvement in treatment resistant posttraumatic stress disorder (PTSD). Data came from the recordings of Mithoefer et al. (2011). In the third therapeutic session studied, patients were assigned, double blind, to an MDMA or a placebo group. Condition-blind scorers listened to therapy recordings and scored utterances where patients initiated topics that were empathic (regarding others' emotions), entactic (requesting or appreciating physical touch), or ensuic (describing a change in their sense of themselves). Patients who received MDMA produced high levels of ensuic, empathic, and entactic utterances compared with those who received the placebo. Interrater discourse scoring was reliable. The relationship between the number of scored utterances and the Clinician Administered PTSD Scale scores measuring PTSD severity after the treatment was significant, and reanalysis grouped bimodally into "many" or "few" such utterances remained significant. MDMA assisted these patients in having meaningful and disorder-resolving thoughts and discourse in talk therapy. PMID- 26998700 TI - Diagnostic yield of cystoscopy in the evaluation of recurrent urinary tract infection in women. AB - AIMS: Due to a paucity of evidence-based guidelines, anecdotal practice patterns often dictate clinical management of recurrent urinary tract infection (UTI) in women. Our aim was to identify pathologic findings of the urinary tract through cystoscopy and imaging in women with recurrent UTI, and to determine if specific risk factors are associated with a higher rate of abnormal findings. METHODS: In a single-institutional cohort, cystoscopy was performed for women with recurrent UTI between 1/2010 and 7/2014. All eligible patients were included in a maintained database and those with gross or microscopic hematuria were excluded. Abdominopelvic imaging was recommended and included in study data when completed. Associations between clinical risk factors (history of renal transplant, urogynecologic surgery, or urolithiasis) and abnormal findings were analyzed by Fisher's exact test. RESULTS: A total of 163 women (mean age 60.6 years) were included in final analysis. Abdominopelvic imaging was available in 133 (82%) cases. Cystoscopy identified 9 (5.5%) cases of significant clinical findings. Of these only 5 (3.8%) cases were uniquely identified on cystoscopy and missed on imaging modalities. When imaging was normal, cystoscopy was also normal in 94% of cases. The examined clinical risk factors were not associated with higher risk of abnormal cystoscopy (P = 0.49) or imaging (P = 0.42). CONCLUSIONS: Cystoscopy performed solely for recurrent UTI is low yield in patients with normal imaging studies, but a small number of abnormal findings may be missed by foregoing this element of the patient workup. No studied risk factor was predictive of an abnormal workup. Neurourol. Urodynam. 36:692-696, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26998702 TI - Quantitative 3D electromagnetic field determination of 1D nanostructures from single projection. AB - One-dimensional (1D) nanostructures have been regarded as the most promising building blocks for nanoelectronics and nanocomposite material systems as well as for alternative energy applications. Although they result in confinement of a material, their properties and interactions with other nanostructures are still very much three-dimensional (3D) in nature. In this work, we present a novel method for quantitative determination of the 3D electromagnetic fields in and around 1D nanostructures using a single electron wave phase image, thereby eliminating the cumbersome acquisition of tomographic data. Using symmetry arguments, we have reconstructed the 3D magnetic field of a nickel nanowire as well as the 3D electric field around a carbon nanotube field emitter, from one single projection. The accuracy of quantitative values determined here is shown to be a better fit to the physics at play than the value obtained by conventional analysis. Moreover the 3D reconstructions can then directly be visualized and used in the design of functional 3D architectures built using 1D nanostructures. PMID- 26998701 TI - Antifungal New Oxepine-Containing Alkaloids and Xanthones from the Deep-Sea Derived Fungus Aspergillus versicolor SCSIO 05879. AB - Phytopathogenic fungi remain a continuous and huge threat in the agricultural fields. The agrochemical industry has made great development of the use of microbial natural products, which has been regarded as an effective strategy against phytopathogenic fungi. Antifungal bioassay-directed fractionation was used to isolate two new oxepine-containing alkaloids (1 and 2), two new 4-aryl quinolin-2-one alkaloids (3 and 4), and four new prenylated xanthones (5-8) from the deep-sea-derived fungus Aspergillus versicolor SCSIO 05879. Extensive NMR spectroscopic analysis, quantum mechanical calculations, and X-ray single-crystal diffraction were used to elucidate their structures, including their absolute configurations. Versicoloids A and B, versicone A, and cottoquinazoline A showed antifungal activities against three phytopathogenic fungi. The antifungal activities of these bioactive compounds strongly depend on the fungal species. Especially versicoloids A and B showed strong fungicidal effect (MIC of 1.6 MUg/mL) against Colletotrichum acutatum, compared with that of the positive control cycloheximide (MIC of 6.4 MUg/mL). The results of antifungal experiments indicated that versicoloids A and B may be regarded as candidate agents of antifungal agrochemicals. PMID- 26998703 TI - Designs for a quantum electron microscope. AB - One of the astounding consequences of quantum mechanics is that it allows the detection of a target using an incident probe, with only a low probability of interaction of the probe and the target. This 'quantum weirdness' could be applied in the field of electron microscopy to generate images of beam-sensitive specimens with substantially reduced damage to the specimen. A reduction of beam induced damage to specimens is especially of great importance if it can enable imaging of biological specimens with atomic resolution. Following a recent suggestion that interaction-free measurements are possible with electrons, we now analyze the difficulties of actually building an atomic resolution interaction free electron microscope, or "quantum electron microscope". A quantum electron microscope would require a number of unique components not found in conventional transmission electron microscopes. These components include a coherent electron beam-splitter or two-state-coupler, and a resonator structure to allow each electron to interrogate the specimen multiple times, thus supporting high success probabilities for interaction-free detection of the specimen. Different system designs are presented here, which are based on four different choices of two state-couplers: a thin crystal, a grating mirror, a standing light wave and an electro-dynamical pseudopotential. Challenges for the detailed electron optical design are identified as future directions for development. While it is concluded that it should be possible to build an atomic resolution quantum electron microscope, we have also identified a number of hurdles to the development of such a microscope and further theoretical investigations that will be required to enable a complete interpretation of the images produced by such a microscope. PMID- 26998704 TI - Integrated biomarkers induced by chlorpyrifos in two different life stages of zebrafish (Danio rerio) for environmental risk assessment. AB - This study was performed to understand how chlorpyrifos (CHL) affects zebrafish (Danio rerio) embryos and adults, by exposing this model organism to various concentrations of the insecticide. The 96-h acute toxicity test to determine the effect of CHL on adult zebrafish yielded a LC50 of 709.43MUg/L(-1). Small molecular weight proteins less than 25kDa and phospholipids were analyzed with MALDI-TOF MS/MS in order to compare expression patterns, revealing that some peaks were dramatically altered after CHL treatment. Whereas no acute toxicity was detected in the embryo toxicity test, malformation of zebrafish larvae was observed, with many individuals harboring curved spines. In an angiogenesis test on larvae of transgenic zebrafish, CHL did not have an inhibitory effect. Relative gene expression analyses using real-time polymerase chain reaction (RT PCR) of DNA from zebrafish embryos revealed that different subtypes of cytochrome P450 (CYP450), such as CYP1A and CYP3A, were significantly up-regulated in response to CHL at a concentration of 400MUg/L(-1) compared to the control. The expression level of NR1I2, a CYP gene transcriptional regulator, UGT1a1, and MDR1 were all up-regulated in the CHL-treated embryos. Finally, the expression level of acetylcholinesterase (AChE) and catalase (CAT) decreased, whereas that of superoxide dismutase (SOD) did not differ significantly. Our results suggest that the up-regulation of metabolic enzymes including CYP450 and MDR1 may be involved in CHL resistance in zebrafish. PMID- 26998705 TI - Effects of a Minimal Workplace Intervention to Reduce Sedentary Behaviors and Improve Perceived Wellness in Middle-Aged Women Office Workers. AB - BACKGROUND: The purpose of this study was to determine whether an alert to get up once per hour while at work would reduce sitting time, increase sit-to-stand transitions, and improve perceived wellness in women with sedentary jobs. METHODS: Female university staff and administrators (48 +/- 10 years) were randomly assigned to control-control (CC) (n = 22) or control-intervention (CI) (n = 22) groups. Both used a thigh-worn postural-based activity monitor for 2 weeks. The CC group maintained normal behaviors, whereas the CI group maintained behaviors during control week, but received hourly alerts on their computer during work hours in the intervention week. Time sitting and sit-to-stand transitions during an 8.5-hour workday were examined. A perceived wellness survey was completed at baseline and after the control and intervention weeks. RESULTS: Among all participants (N = 44) during the control week, 68% of the workday was spent sitting and 41 sit-to-stand transitions occurred. An analysis of variance revealed no statistically significant differences in variables over time (P > .05). There was a significant increase in perceived wellness from baseline in both groups (P <= .05). Perceived wellness showed no statistically significant difference between groups. CONCLUSIONS: The intervention had no statistically significant effect on sitting time or sit-to-stand transitions. Participation improved perceived wellness in the absence of behavior change. PMID- 26998706 TI - Alvocidib (flavopiridol) for the treatment of chronic lymphocytic leukemia. AB - INTRODUCTION: Alvocidib, which has orphan drug designation in chronic lymphocytic leukemia (CLL) from the FDA and the EMA, is a plant-derived semisynthetic flavone that acts as a cyclin-dependent kinase inhibitor. It induces apoptosis in CLL cells in vitro and was introduced into clinical trials in CLL as an intravenous infusion in 1997, which proved disappointing. Since the drug avidly binds to plasma proteins, higher serum concentrations were required for clinical antileukemia activity than those suggested by in vitro studies. Subsequent studies utilizing bolus plus infusional doses revealed significant activity against CLL, even in patients with unfavorable characteristics. However, significant toxicity including high rates of major tumor lysis syndrome, cytokine release syndrome and secretory diarrhea were also observed. AREAS COVERED: The chemistry, pharmacodynamics, pharmacokinetics and metabolism of alvocidib are briefly discussed and phase I-II studies in CLL are discussed in detail. To date, no phase III studies in CLL have been reported. EXPERT OPINION: A number of much less toxic drugs with similar efficacy against CLL both with and without unfavorable cytogenetics have come to market. Furthermore, enthusiasm for the development of alvocidib as a single agent for the treatment of CLL has waned, primarily due to its toxicity. PMID- 26998707 TI - Women's Fat Talk Can "Kill the Mood" for Men. AB - This study examined men's perceptions of women engaging in "Fat Talk," a style of conversation that expresses discontent towards one's physical appearance, especially focusing on and criticizing body fat, shape, and weight. Male undergraduates were shown a vignette illustrating a courting scenario wherein the target female's body size was manipulated to be "sexy" and: (a) "lean," (b) "average," or (c) "larger." And to another woman, the men overheard the target female either: (a) self-degrade herself (fat talk) or (b) self-accept herself. As a third independent variable, participants' self esteem was divided into high and low with a median split. Dependent variables included self-created Likert items on his attraction towards the target and perceptions of her health and popularity. Men found the target female to have poorer mental health when he overheard her fat talking versus self-accepting. Further, his desire for a more exclusive committed relationship was stronger when she was described as leaner, especially for the lower self-esteemed men. As a pilot study, this has implications for interventions to decrease women's fat talk and begins research on the dynamic interplay between women's fat talk and heterosexual courtships. PMID- 26998709 TI - Repeat-based Sequence Typing of Carnobacterium maltaromaticum. AB - Carnobacterium maltaromaticum is a Lactic Acid Bacterium (LAB) of technological interest for the food industry, especially the dairy as bioprotection and ripening flora. The industrial use of this LAB requires accurate and resolutive typing tools. A new typing method for C. maltaromaticum inspired from MLVA analysis and called Repeat-based Sequence Typing (RST) is described. Rather than electrophoresis analysis, our RST method is based on sequence analysis of multiple loci containing Variable-Number Tandem-Repeats (VNTRs). The method described here for C. maltaromaticum relies on the analysis of three VNTR loci, and was applied to a collection of 24 strains. For each strain, a PCR product corresponding to the amplification of each VNTR loci was sequenced. Sequence analysis allowed delineating 11, 11, and 12 alleles for loci VNTR-A, VNTR-B, and VNTR-C, respectively. Considering the allele combination exhibited by each strain allowed defining 15 genotypes, ending in a discriminatory index of 0.94. Comparison with MLST revealed that both methods were complementary for strain typing in C. maltaromaticum. PMID- 26998708 TI - Changes in Prescription and Over-the-Counter Medication and Dietary Supplement Use Among Older Adults in the United States, 2005 vs 2011. AB - IMPORTANCE: Prescription and over-the-counter medicines and dietary supplements are commonly used, alone and together, among older adults. However, the effect of recent regulatory and market forces on these patterns is not known. OBJECTIVES: To characterize changes in the prevalence of medication use, including concurrent use of prescription and over-the-counter medications and dietary supplements, and to quantify the frequency and types of potential major drug-drug interactions. DESIGN, SETTING, AND PARTICIPANTS: Descriptive analyses of a longitudinal, nationally representative sample of community-dwelling older adults 62 to 85 years old. In-home interviews with direct medication inspection were conducted in 2005-2006 and again in 2010-2011. The dates of the analysis were March to November 2015. We defined medication use as the use of at least 1 prescription or over-the-counter medication or dietary supplement at least daily or weekly and defined concurrent use as the regular use of at least 2 medications. We used Micromedex to identify potential major drug-drug interactions. MAIN OUTCOMES AND MEASURES: Population estimates of the prevalence of medication use (in aggregate and by therapeutic class), concurrent use, and major drug-drug interactions. RESULTS: The study cohort comprised 2351 participants in 2005-2006 and 2206 in 2010-2011. Their mean age was 70.9 years in 2005-2006 and 71.4 years in 2010 2011. Fifty-three percent of participants were female in 2005-2006, and 51.6% were female in 2010-2011. The use of at least 1 prescription medication slightly increased from 84.1% in 2005-2006 to 87.7% in 2010-2011 (P = .003). Concurrent use of at least 5 prescription medications increased from 30.6% to 35.8% (P = .02). While the use of over-the-counter medications declined from 44.4% to 37.9%, the use of dietary supplements increased from 51.8% to 63.7% (P < .001 for both). There were clinically significant increases in the use of statins (33.8% to 46.2%), antiplatelets (32.8% to 43.0%), and omega-3 fish oils (4.7% to 18.6%) (P < .05 for all). In 2010-2011, approximately 15.1% of older adults were at risk for a potential major drug-drug interaction compared with an estimated 8.4% in 2005-2006 (P < .001). Most of these interacting regimens involved medications and dietary supplements increasingly used in 2010-2011. CONCLUSIONS AND RELEVANCE: In this study, the use of prescription medications and dietary supplements, and concurrent use of interacting medications, has increased since 2005, with 15% of older adults potentially at risk for a major drug-drug interaction. Improving safety with the use of multiple medications has the potential to reduce preventable adverse drug events associated with medications commonly used among older adults. PMID- 26998710 TI - Subdural Collection as Initial Presentation of Granulomatosis With Polyangiitis. PMID- 26998711 TI - Genomic structure and expression of immunoglobulins in Squamata. AB - The Squamata order represents a major evolutionary reptile lineage, yet the structure and expression of immunoglobulins in this order has been scarcely studied in detail. From the genome sequences of four Squamata species (Gekko japonicus, Ophisaurus gracilis, Pogona vitticeps and Ophiophagus hannah) and RNA seq datasets from 18 other Squamata species, we identified the immunoglobulins present in these animals as well as the tissues in which they are found. All Squamata have at least three immunoglobulin classes; namely, the immunoglobulins M, D, and Y. Unlike mammals, however, we provide evidence that some Squamata lineages possess more than one CMU gene which is located downstream from the Cdelta gene. The existence of two evolutionary lineages of immunoglobulin Y is shown. Additionally, it is demonstrated that while all Squamata species possess the lambda light chain, only Iguanidae species possess the kappa light chain. PMID- 26998712 TI - Derivation of original RESP atomic partial charges for MD simulations of the LDAO surfactant with AMBER: applications to a model of micelle and a fragment of the lipid kinase PI4KA. AB - In this paper, we describe the derivation and the validation of original RESP atomic partial charges for the N, N-dimethyl-dodecylamine oxide (LDAO) surfactant. These charges, designed to be fully compatible with all the AMBER force fields, are at first tested against molecular dynamics simulations of pure LDAO micelles and with a fragment of the lipid kinase PIK4A (DI) modeled with the QUARK molecular modeling server. To model the micelle, we used two distinct AMBER force fields (i.e. Amber99SB and Lipid14) and a variety of starting conditions. We find that the micelle structural properties (such as the shape, size, the LDAO headgroup hydration, and alkyl chain conformation) slightly depend on the force field but not on the starting conditions and more importantly are in good agreement with experiments and previous simulations. We also show that the Lipid14 force field should be used instead of the Amber99SB one to better reproduce the C(sp3)C(sp3)C(sp3)C(sp3) conformation in the surfactant alkyl chain. Concerning the simulations with LDAO-DI protein, we carried out different runs at two NaCl concentrations (i.e. 0 and 300 mM) to mimic, in the latter case, the experimental conditions. We notice a small dependence of the simulation results with the LDAO parameters and the salt concentration. However, we find that in the simulations, three out of four tryptophans of the DI protein are not accessible to water in agreement with our fluorescence spectroscopy experiments reported in the paper. PMID- 26998713 TI - A new technology of CO2 supplementary for microalgae cultivation on large scale - A spraying absorption tower coupled with an outdoor open runway pond. AB - An effective CO2 supply system of a spraying absorption tower combined with an outdoor ORWP (open raceway pond) for microalgae photoautotrophic cultivation is developed in this paper. The microalgae yield, productivity and CO2 fixation efficiency were investigated, and compared with those of bubbling method. The maximum yield and productivity of biomass were achieved 0.927gL(-1) and 0.114gL( 1)day(-1), respectively. The fixation efficiency of CO2 by microalgae with the spraying tower reached 50%, whereas only 11.17% for bubbling method. Pure CO2 can be used in the spraying absorption tower, and the flow rate was only about one third of the bubbling cultivation. It shows that this new method of quantifiable control CO2 supply can meet the requirements of the growth of microalgae cultivation on large-scale. PMID- 26998714 TI - Effect of the Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) on Corneal Endothelial Wound Healing. AB - PURPOSE: Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as a glaucoma and ocular hypertension treatment in Japan in 2014. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelial injuries. METHODS: Cultured human corneal endothelial cells (HCECs) were treated with ripasudil, and 5-bromo-2'-deoxyuridine (BrdU) incorporation was evaluated by ELISA. A rabbit corneal endothelial damage model was also created by mechanically scraping the corneal endothelium, followed by topical ripasudil eye drop application for 2 weeks. The anterior segment was evaluated by slit-lamp microscopy, and central corneal thickness was measured by ultrasound pachymetry. Corneal specimens were evaluated by phalloidin staining and immunohistochemical analysis using antibodies against Ki67, N-cadherin, and Na+/K+-ATPase. RESULTS: Many more BrdU-positive cells were observed among the HCECs treated with ripasudil (0.3-30 MUM) than among the control HCECs. Ripasudil-treated eyes in a rabbit model showed 91.5 +/- 2.0% Ki67-positive cells after 48 hours, whereas control eyes showed 52.6 +/- 1.3%. Five of six corneas became transparent in ripasudil-treated eyes, whereas zero of six corneas became transparent in the control eyes. Regenerated cell densities were higher in the eyes treated with ripasudil than in eyes treated with vehicle. Eyes treated with ripasudil expressed N-cadherin and Na+/K+-ATPase in almost all CECs, whereas this expression was decreased in control eyes. CONCLUSIONS: Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery. PMID- 26998715 TI - Evaluation of Lamina Cribrosa and Choroid in Nonglaucomatous Patients With Pseudoexfoliation Syndrome Using Spectral-Domain Optical Coherence Tomography. AB - PURPOSE: To evaluate the lamina cribrosa (LC) and peripapillary choroid in patients with pseudoexfoliation syndrome (PXS). METHODS: In this cross-sectional study, one eye each of 32 nonglaucomatous PXS cases and 29 healthy volunteers were enrolled. The optic discs were scanned using enhanced depth imaging spectral domain optical coherence tomography, and measurements were obtained using HEYEX software 6.0. LC and other related variables at three areas (mid-superior, center, and mid-inferior) and peripapillary choroidal thickness were determined. Linear mixed modeling was used to adjust the variables. RESULTS: After adjustment for age, sex, and axial length, there was no significant difference between the two groups in peripapillary choroidal thickness or in retinal nerve fiber layer thickness. The LC was significantly thinner in all three areas in the PXS group when compared with the control group, even after adjustment. Although no significant difference in central laminar depth was observed between the two groups (P = 0.74), the superior and inferior laminar depth were significantly deeper in the PXS group when compared with the control group (P = 0.04 and P = 0.006, respectively). Although there was a significant negative association between age and central choroidal thickness in the control group (beta = -2.820, P = 0.02), this correlation was not significant in the PXS group. CONCLUSIONS: We found that LC is significantly thinner in all three areas of the optic nerve head in nonglaucomatous PXS patients than in controls. Although no significant difference in peripapillary choroidal thickness was observed between the two groups, peripheral posterior displacement of LC in nonglaucomatous PXS eyes was noted. PMID- 26998716 TI - Infantile Nystagmus and Abnormalities of Conjugate Eye Movements in Down Syndrome. AB - PURPOSE: Subjects with Down syndrome (DS) have an anatomical defect within the cerebellum that may impact downstream oculomotor areas. This study characterized gaze holding and gains for smooth pursuit, saccades, and optokinetic nystagmus (OKN) in DS children with infantile nystagmus (IN). METHODS: Clinical data of 18 DS children with IN were reviewed retrospectively. Subjects with constant strabismus were excluded to remove any contribution of latent nystagmus. Gaze holding, horizontal and vertical saccades to target steps, horizontal smooth pursuit of drifting targets, OKN in response to vertically or horizontally oriented square wave gratings drifted at 15 degrees /s, 30 degrees /s, and 45 degrees /s were recorded using binocular video-oculography. Seven subjects had additional optical coherence tomography imaging. RESULTS: Infantile nystagmus was associated with one or more gaze-holding instabilities (GHI) in each subject. The majority of subjects had a combination of conjugate horizontal jerk with constant or exponential slow-phase velocity, asymmetric or symmetric, and either monocular or binocular pendular nystagmus. Six of seven subjects had mild (Grade 0-1) persistence of retinal layers overlying the fovea, similar to that reported in DS children without nystagmus. All subjects had abnormal gains across one or more stimulus conditions (horizontal smooth pursuit, saccades, or OKN). Saccade velocities followed the main sequence. CONCLUSIONS: Down syndrome subjects with IN show a wide range of GHI and abnormalities of conjugate eye movements. We propose that these ocular motor abnormalities result from functional abnormalities of the cerebellum and/or downstream oculomotor circuits, perhaps due to extensive miswiring. PMID- 26998717 TI - Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations. AB - PURPOSE: To determine the prevalence of reticular pseudodrusen (RPD) and their detection using multimodal imaging in patients with bilateral large drusen, and examine their clinical, demographic, environmental, and genetic associations. METHODS: Three hundred participants with bilateral large drusen (>125 MUm) underwent color fundus photography (CFP), near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT) imaging. Demographic information, smoking, and medical history were recorded, and a blood sample was obtained and genotyped to identify the risk alleles of the CFH and ARMS2 genes. RESULTS: Reticular pseudodrusen were detected in 28.2% eyes of 29.0% participants using NIR and SD-OCT combined, but CFP and FAF detected only 42% and 89%, respectively, of these eyes with RPD. Participants with RPD were significantly older than those without (P < 0.001), but there was no significant difference in sex distribution, smoking history, cardiovascular factors, and minor allele frequency of the CFH gene (P > 0.173). However, the minor allele frequency of the ARMS2 gene was significantly higher in participants with RPD (P = 0.002). The presence of RPD was also independently associated with the presence of atrophic changes (including nascent geographic atrophy and drusen-associated atrophy detected on SD-OCT; P = 0.043). CONCLUSIONS: Reticular pseudodrusen were detected on NIR and SD-OCT in more than a quarter of participants with bilateral large drusen, being often overlooked with CFP. Those with RPD had a higher frequency of the ARMS2 risk variant, and eyes with RPD were more likely to have atrophic changes. These findings are important to consider when managing patients with intermediate AMD. PMID- 26998718 TI - The Soluble Guanylate Cyclase Stimulator IWP-953 Increases Conventional Outflow Facility in Mouse Eyes. AB - PURPOSE: The nitric oxide (NO)-cyclic guanosine-3',5'-monophosphate (cGMP) pathway regulates aqueous humor outflow and therefore, intraocular pressure. We investigated the pharmacologic effects of the soluble guanylate cyclase (sGC) stimulator IWP-953 on primary human trabecular meshwork (HTM) cells and conventional outflow facility in mouse eyes. METHODS: Cyclic GMP levels were determined in vitro in HEK-293 cells and four HTM cell strains (HTM120/HTM123: predominantly myofibroblast-like phenotype, HTM130/HTM141: predominantly endothelial-like phenotype), and in HTM cell culture supernatants. Conventional outflow facility was measured following intracameral injection of IWP-953 or DETA NO using a computerized pressure-controlled perfusion system in enucleated mouse eyes ex vivo. RESULTS: IWP-953 markedly stimulated cGMP production in HEK-293 cells in the presence and absence of DETA-NO (half maximal effective concentrations: 17 nM, 9.5 MUM). Similarly, IWP-953 stimulated cGMP production in myofibroblast-like HTM120 and HTM123 cells, an effect that was greatly amplified by the presence of DETA-NO. In contrast, IWP-953 stimulation of cGMP production in endothelial-like HTM130 and HTM141 cells was observed, but was markedly less prominent than in HTM120 and HTM123 cells. Notably, cGMP was found in all HTM culture supernatants, following IWP-953/DETA-NO stimulation. In paired enucleated mouse eyes, IWP-953 at 10, 30, 60, and 100 MUM concentration-dependently increased outflow facility. This effect (89.5%) was maximal at 100 MUM (P = 0.002) and in magnitude comparable to DETA-NO at 100 MUM (97.5% increase, P = 0.030). CONCLUSIONS: These data indicate that IWP-953, via modulation of the sGC cGMP pathway, increases aqueous outflow facility in mouse eyes, suggesting therapeutic potential for sGC stimulators as novel ocular hypotensive drugs. PMID- 26998719 TI - The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction. AB - PURPOSE: The translational repressor 4E-BP1 interacts with the mRNA cap-binding protein eIF4E and thereby promotes cap-independent translation of mRNAs encoding proteins that contribute to diabetic retinopathy. Interaction of 4E-BP1 with eIF4E is enhanced in the retina of diabetic rodents, at least in part, as a result of elevated 4E-BP1 protein expression. In the present study, we examined the role of 4E-BP1 in diabetes-induced visual dysfunction, as well as the mechanism whereby hyperglycemia promotes 4E-BP1 expression. METHODS: Nondiabetic and diabetic wild-type and 4E-BP1/2 knockout mice were evaluated for visual function using a virtual optomotor test (Optomotry). Retinas were harvested from nondiabetic and type 1 diabetic mice and analyzed for protein abundance and posttranslational modifications. Similar analyses were performed on cells in culture exposed to hyperglycemic conditions or an O-GlcNAcase inhibitor (Thiamet G [TMG]). RESULTS: Diabetes-induced visual dysfunction was delayed in mice deficient of 4E-BP1/2 as compared to controls. 4E-BP1 protein expression was enhanced by hyperglycemia in the retina of diabetic rodents and by hyperglycemic conditions in retinal cells in culture. A similar elevation in 4E-BP1 expression was observed with TMG. The rate of 4E-BP1 degradation was significantly prolonged by either hyperglycemic conditions or TMG. A PEST motif in the C-terminus of 4E BP1 regulated polyubiquitination, turnover, and binding of an E3 ubiquitin ligase complex containing CUL3. CONCLUSIONS: The findings support a model whereby elevated 4E-BP1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of 4E-BP1 within its PEST motif. PMID- 26998720 TI - QSAR models for predicting octanol/water and organic carbon/water partition coefficients of polychlorinated biphenyls. AB - Quantitative structure-property relationship modelling can be a valuable alternative method to replace or reduce experimental testing. In particular, some endpoints such as octanol-water (KOW) and organic carbon-water (KOC) partition coefficients of polychlorinated biphenyls (PCBs) are easier to predict and various models have been already developed. In this paper, two different methods, which are multiple linear regression based on the descriptors generated using Dragon software and hologram quantitative structure-activity relationships, were employed to predict suspended particulate matter (SPM) derived log KOC and generator column, shake flask and slow stirring method derived log KOW values of 209 PCBs. The predictive ability of the derived models was validated using a test set. The performances of all these models were compared with EPI SuiteTM software. The results indicated that the proposed models were robust and satisfactory, and could provide feasible and promising tools for the rapid assessment of the SPM derived log KOC and generator column, shake flask and slow stirring method derived log KOW values of PCBs. PMID- 26998721 TI - Cancer Risks in U.S. Radiologic Technologists Working With Fluoroscopically Guided Interventional Procedures, 1994-2008. AB - OBJECTIVE: The purpose of this study was to examine risks of cancer incidence and mortality among U.S. radiation technologists performing or assisting with fluoroscopically guided interventional procedures. SUBJECTS AND METHODS: A nationwide prospective cohort of 90,957 radiologic technologists, who responded to a 1994-1998 survey that collected information on whether they had ever worked with fluoroscopically guided interventional procedures, was followed through completion of a subsequent cohort survey during 2003-2005 (for cancer incidence) or December 31, 2008 (for cancer mortality). Sex-adjusted hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazards models for incidence and mortality from all cancers other than nonmelanoma skin cancer and for specific cancer outcomes in participants who reported ever performing fluoroscopically guided interventional procedures compared with technologists who never performed these procedures. RESULTS: The analysis showed an approximately twofold increased risk of brain cancer mortality (HR, 2.55; 95% CI, 1.48-4.40) and modest elevations in incidence of melanoma (HR, 1.30; 95% CI, 1.05-1.61) and in breast cancer incidence (HR, 1.16; 95% CI, 1.02-1.32) but not mortality (HR, 1.07; 95% CI, 0.69-1.66) among technologists who performed fluoroscopically guided interventional procedures compared with those who never performed these procedures. Although there was a small suggestive increase in incidence of all cancers combined, excluding nonmelanoma skin cancers (HR, 1.08; 95% CI, 1.00 1.17), mortality from all cancers combined, excluding nonmelanoma skin cancers, was not elevated (HR, 1.00; 95% CI, 0.88-1.14). We similarly observed no elevated risk of cancers of the thyroid, skin other than melanoma, prostate, lung, or colon and rectum or of leukemia that was not chronic lymphocytic leukemia among workers who performed fluoroscopically guided interventional procedures. CONCLUSION: We observed elevated risks of brain cancer, breast cancer, and melanoma among technologists who performed fluoroscopically guided interventional procedures. Although exposure to low-dose radiation is one possible explanation for these increased risks, these results may also be due to chance or unmeasured confounding by nonradiation risk factors. Our results must be confirmed in other studies, preferably with individual radiation dose data. PMID- 26998722 TI - Role of small biotechnology companies in the fledgling biodefense vaccine industry. PMID- 26998723 TI - Assessment of DNA damage in car spray painters exposed to organic solvents by the high-throughput comet assay. AB - Occupational exposure as a painter is associated with DNA damage and development of cancer. Comet assay has been widely adopted as a sensitive and quantitative tool for DNA damage assessment at the individual cell level in populations exposed to genotoxics. The aim of this study was to assess the application of the high-throughput comet assay, to determine the DNA damage in car spray painters. The study population included 52 car spray painters and 52 unexposed subjects. A significant increase in the %TDNA median (p < 0.001) was observed in the exposed group in comparison to the unexposed group. Neither age (%TDNA: p = 0.913) nor time of exposure (%TDNA: p = 0.398) were significantly correlated with DNA damage. The car spray painters who consumed alcohol did not show a significant increase in DNA damage compared to nonalcohol consumers (p > 0.05). The results showed an increase in DNA breaks in car spray painters exposed to organic solvents and paints; furthermore, they demonstrated the application of high throughput comet assay in an occupational exposure study to genotoxic agents. PMID- 26998724 TI - New use of an old drug: chloroquine reduces viral and ALT levels in HCV non responders (a randomized, triple-blind, placebo-controlled pilot trial). AB - Hepatitis C virus (HCV) infection induces autophagy, but the virus assimilates the autophagic response into its own life cycle. Chloroquine (CQ) is an autophagy inhibitor that is clinically used to treat malaria. The aims of this pilot clinical trial were to evaluate the therapeutic potential and short-term safety of CQ in patients with chronic HCV genotype 1, who were unresponsive to a combination of pegylated interferon alpha and ribavirin. Ten non-responders to previous antiviral treatment(s) were randomized to receive either CQ (150 mg daily for 8 weeks) or placebo, and were followed for 4 weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week 4 (initial response), week 8 (end-of-treatment response), and at the end of 12 weeks. A significant decrease in HCV RNA after the treatments (week 8) was observed in all patients in the CQ group (P = 0.04). However, HCV RNA levels increased within 4 weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalized during treatment in the CQ group. However, this response was also lost after treatment cessation. This study provides preliminary evidence that CQ is possibly a safe treatment option for HCV non-responders. PMID- 26998725 TI - Aclidinium bromide inhalation powder for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease including chronic bronchitis and emphysema. AB - Aclidinium is a twice-daily long-acting muscarinic receptor antagonist (LAMA) with an interesting pharmacological profile. Recent evidence indicates that this LAMA, in addition to causing a significant improvement in lung function and other important supportive outcomes, such as health related quality of life, dyspnea and nighttime/early morning symptoms in patients suffering from COPD, is also able to significantly reduce the rate of exacerbations of any severity, is extremely effective in controlling the COPD symptoms, is able to reduce lung hyperinflation, and has an excellent cardiovascular safety profile. Consequently, aclidinium should be considered a first-line approach at least for the symptomatic treatment of COPD although there are still few head-to-head studies comparing this LAMA with other bronchodilators. In any case, aclidinium can be taken into account in the treatment of different COPD phenotypes (emphysema, chronic bronchitis, exacerbators and patients with overlap COPD asthma). PMID- 26998726 TI - Salivary Gland Enlargement as an Unusual Imaging Manifestation of Granulomatosis With Polyangiitis Involving the Head and Neck Region. PMID- 26998728 TI - Photocatalytic oxidation of H2S in the gas phase over TiO2-coated glass fiber filter. AB - To promote the photocatalytic oxidation (PCO) of hydrogen sulfide (H2S) in the gas phase, TiO2-coated glass fiber filters were packed in an annular photoreactor. Glass fibers coated with TiO2 thin films were characterized structurally and morphologically by field emission gun scanning electron microscopy (FEG-SEM), scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDS) and X-ray diffractometry (XRD). Flow rate and H2S inlet concentration were evaluated to determine the performance of the reactor. Removal efficiencies up to 99% were achieved for flow rate of 25 L h(-1) (residence time of 121 s) and H2S inlet concentration from 12 to 14 ppmv. The long-term experiment presented H2S removal of 89% for 16 h. After 28 h of continuous use, H2S degradation was observed at 64%, which suggests that the photocatalyst was losing activity due to deactivation. Moreover, the kinetics of the PCO of H2S according to the Langmuir-Hinshelwood (L-H) approach along with the mass balance of a plug-flow reactor was modeled. The reaction constant (k) was calculated at approximately 10.5 MUmol m(-3) s(-1) and the adsorption constant (K) of approximately 5263 m(-3) mol with linearity (R2) of 0.98. PMID- 26998729 TI - Fundamental developments in clinical infrared and Raman spectroscopy. PMID- 26998730 TI - Synergetic Integration of Cu1.94S-ZnxCd1-xS Heteronanorods for Enhanced Visible Light-Driven Photocatalytic Hydrogen Production. AB - In this Communication, we present the integration of synergetic designs into high quality, well-defined Cu1.94S-ZnxCd1-xS heteronanorods (0 <= x <= 1) for enhanced photocatalytic hydrogen evolution. These heteronanorods possess two light absorbers, intimate heterointerfaces, tunable band gaps over a wide range, and uniform one-dimensional morphology. As verified by experimental and density functional theory studies, these heteronanorods with continuous composition adjustment fully exploit the benefits of both interfacial charge separation and optimized band alignments. Even without any cocatalysts, Cu1.94S-Zn0.23Cd0.77S heteronanorods exhibit efficient hydrogen production activity (7735 MUmol h(-1) g(-1)) under visible-light irradiation (lambda > 420 nm), representing a 59-fold enhancement compared with the pristine CdS catalyst. Meanwhile, deposition of a Pt cocatalyst on the Cu1.94S-ZnxCd1-xS surface substantially enhances the hydrogen production performance (13 533 MUmol h(-1) g(-1)) with an apparent quantum efficiency of 26.4% at 420 nm, opening up opportunities to promote the overall photocatalytic performance using rationally designed nanostructures. PMID- 26998731 TI - Surface-Adaptive, Antimicrobially Loaded, Micellar Nanocarriers with Enhanced Penetration and Killing Efficiency in Staphylococcal Biofilms. AB - Biofilms cause persistent bacterial infections and are extremely recalcitrant to antimicrobials, due in part to reduced penetration of antimicrobials into biofilms that allows bacteria residing in the depth of a biofilm to survive antimicrobial treatment. Here, we describe the preparation of surface-adaptive, Triclosan-loaded micellar nanocarriers showing (1) enhanced biofilm penetration and accumulation, (2) electrostatic targeting at acidic pH toward negatively charged bacterial cell surfaces in a biofilm, and (3) antimicrobial release due to degradation of the micelle core by bacterial lipases. First, it was established that mixed-shell-polymeric-micelles (MSPM) consisting of a hydrophilic poly(ethylene glycol) (PEG)-shell and pH-responsive poly(beta-amino ester) become positively charged at pH 5.0, while being negatively charged at physiological pH. This is opposite to single-shell-polymeric-micelles (SSPM) possessing only a PEG-shell and remaining negatively charged at pH 5.0. The stealth properties of the PEG-shell combined with its surface-adaptive charge allow MSPMs to penetrate and accumulate in staphylococcal biofilms, as demonstrated for fluorescent Nile red loaded micelles using confocal-laser scanning-microscopy. SSPMs, not adapting a positive charge at pH 5.0, could not be demonstrated to penetrate and accumulate in a biofilm. Once micellar nanocarriers are bound to a staphylococcal cell surface, bacterial enzymes degrade the MSPM core to release its antimicrobial content and kill bacteria over the depth of a biofilm. This constitutes a highly effective pathway to control blood-accessible staphylococcal biofilms using antimicrobials, bypassing biofilm recalcitrance to antimicrobial penetration. PMID- 26998732 TI - On the structural denaturation of biological analytes in trapped ion mobility spectrometry - mass spectrometry. AB - Key to native ion mobility/mass spectrometry is to prevent the structural denaturation of biological molecules in the gas phase. Here, we systematically assess structural changes induced in the protein ubiquitin during a trapped ion mobility spectrometry (TIMS) experiment. Our analysis shows that the extent of structural denaturation induced in ubiquitin ions is largely proportional to the amount of translational kinetic energy an ion gains from the applied electric field between two collisions with buffer gas particles. We then minimize the efficiency of the structural denaturation of ubiquitin ions in the gas phase during a TIMS experiment. The resulting "soft" TIMS spectra of ubiquitin are found largely identical to those observed on "soft" elevated-pressure ion mobility drift tubes and the corresponding calibrated cross sections are consistent with structures reported from NMR experiments for the native and A state of ubiquitin. Thus, our analysis reveals that TIMS is useful for native ion mobility/mass spectrometry analysis. PMID- 26998734 TI - Longitudinal Study of Mental Health and Pain-Related Functioning Following a Motor Vehicle Collision. AB - OBJECTIVE: Relations between mental and physical health symptoms are well established in the literature on recovery following motor vehicle collisions (MVCs). To understand the temporal sequencing and evolution of these relations, we examined the bidirectional association between mental and physical health symptoms at 4 and 16 weeks following a MVC. METHODS: The sample consisted of 103 participants recruited through public MVC police reports. The study included self report assessments for posttraumatic stress symptoms, depressive symptoms, bodily pain, and role limitations attributable to physical health. A series of multivariable linear regression analyses were conducted to estimate the associations between these mental and physical health outcomes. RESULTS: The analysis revealed that mental health symptoms at 4 weeks post-MVC were associated with higher bodily pain at 16 weeks post-MVC (PTSD symptoms: beta = -0.74, 95% CI: -1.06, -0.42; depressive symptoms: beta = -1.34, 95% CI: -1.90, -0.78), but not higher health-related role limitations. Physical health symptoms at 4 weeks post-MVC were not associated with PTSD or depressive symptoms at 16 weeks post MVC. CONCLUSIONS: The results indicate the predictive strength of mental health symptoms at 4 weeks post-MVC in identifying individuals at risk for bodily pain at 16 weeks and shed light on the temporal sequencing of how relations between physical and mental health symptoms emerge over time. This suggests that early assessment of mental health symptoms may have significant implications for the treatment of these patients. (PsycINFO Database Record PMID- 26998733 TI - Youth reports of parents' romantic relationship quality: Links to physical health. AB - OBJECTIVE: Prior work has shown that negative aspects (e.g., conflict) of marriage or marriage-like relationships are associated with poor health of offspring, but much less is known about the effects of positive aspects (e.g., affection) of parental romantic relationships. This study investigated links between conflict and affection within parents' romantic relationships and the health of youth with asthma. METHOD: Eighty youths with asthma aged 10-17 answered daily questions over a 4-day period about conflict and affection within their parents' romantic relationship, as well as their own daily mood, asthma symptoms, and expiratory peak flow. RESULTS: Multiple regression analyses revealed that romantic affection-but not conflict-was directly associated with higher expiratory peak flow. Further, there was a significant indirect effect of romantic affection via youth positive affect on lower asthma symptoms. CONCLUSION: These results are the first to our knowledge to demonstrate that youth-reported positive characteristics of parents' romantic relationships are associated with better health among youth with asthma. (PsycINFO Database Record PMID- 26998735 TI - Collaborative and Overinvolved Parenting Differentially Predict Outcomes in Adolescents With Type 1 Diabetes. AB - OBJECTIVE: The current study examined the impact of collaborative and intrusive parenting on depression and glycemic control in children with Type 1 diabetes (T1D). Research examining the association between parenting and child adjustment in this population has been limited by a reliance primarily on questionnaire data and cross-sectional analyses. To address these gaps, the current study used an observational coding system to measure the effects of parenting on child adjustment over a 1-year period. METHOD: Youth (10 to 16 years old) with T1D and their mothers (N = 81) were recruited from an outpatient pediatrics diabetes clinic. Mothers' symptoms of anxiety and depression and children's depressive symptoms were assessed by self- reports; parenting behaviors were assessed via video-recorded observations coded using the Iowa Family Interaction Rating Scales; and adolescents' glycosylated hemoglobin (HbA1c) was obtained from medical records. RESULTS: Bivariate correlations and linear regression analyses revealed that higher levels of observed collaborative parenting were related to significantly lower HbA1c 12 months later, and higher levels of observed overinvolved parenting were related to significantly greater child depressive symptoms 12 months later. Further, age and treatment type moderated the relation between overinvolved parenting and child depressive symptoms. CONCLUSIONS: Collaborative and overinvolved parenting appears important for adolescents in predicting both psychological and health-related outcomes over time. Parenting behaviors may serve as an important target for future interventions to enhance adjustment in these children. (PsycINFO Database Record PMID- 26998736 TI - Enhanced Gas Sensitivity and Selectivity on Aperture-Controllable 3D Interconnected Macro-Mesoporous ZnO Nanostructures. AB - Three-dimensional (3D) macro-mesoporous structures demonstrate effective performance for gas sensing. In this work, we have designed and successfully prepared aperture-controllable three-dimensional interconnected macro-mesoporous ZnO (3D-IMM-ZnO) nanostructures by template-based layer-by-layer filtration deposition. XRD, SEM, and TEM have been used to characterize the obtained hexagonal wurzite 3D-IMM-ZnO nanostructures. Owing to its special 3D interconnected hierarchically porous structure, the 3D-IMM-ZnO nanostructures exhibit excellent gas sensing performances toward acetone and methanol. The 3D IMM-ZnO nanostructure with the largest macropore demonstrates the best gas sensitivity owing to its largest cavity providing enough space for gas diffusion. On the basis of the results and analyses, we propose that the synergistic effect of electron liberation and electron density of acetone and the special structure make the 3D-IMM-ZnO nanostructures demonstrate better gas sensing properties than many other porous ZnO nanostructures and preferred selectivity to acetone. PMID- 26998737 TI - Insights into the Thiamine Diphosphate Enzyme Activation Mechanism: Computational Model for Transketolase Using a Quantum Mechanical/Molecular Mechanical Method. AB - We propose the first computational model for transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, using a quantum mechanical/molecular mechanical method on the basis of crystallographic TK structures from yeast and Escherichia coli, together with experimental kinetic data reported in the literature with wild-type and mutant TK. This model allowed us to define a new route for ThDP activation in the enzyme environment. We evidenced a strong interaction between ThDP and Glu418B of the TK active site, itself stabilized by Glu162A. The crucial point highlighted here is that deprotonation of ThDP C2 is not performed by ThDP N4' as reported in the literature, but by His481B, involving a HOH688A molecule bridge. Thus, ThDP N4' is converted from an amino form to an iminium form, ensuring the stabilization of the C2 carbanion or carbene. Finally, ThDP activation proceeds via an intermolecular process and not by an intramolecular one as reported in the literature. More generally, this proposed ThDP activation mechanism can be applied to some other ThDP-dependent enzymes and used to define the entire TK mechanism with donor and acceptor substrates more accurately. PMID- 26998738 TI - Re(CO)3-Templated Formation of Aza(dibenzo)dipyrromethenes. AB - The Re(CO)3 unit was used to template the formation of aza(dibenzopyrro)methene (ADBM) in the presence of pyridine or N-methylimidazole. The products of these template reactions are six-coordinate complexes, with a facial arrangement of the carbonyls, a bidentate ADBM, and a sixth ligand (pyridine or N-methylimiadozle). Three types of ADBM ligands are produced from these reactions, depending on the degree of hydrolysis; bis(imine)-terminated, bis(oxo)-terminated, and mixed imine/oxo chelates were formed. PMID- 26998739 TI - Outcomes of Lung Transplantation in Recipients With Hepatitis C Virus Infection. AB - Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV-positive, compared to 443 HCV-negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1-, 3-, and 5 year survival were similar in HCV RNA-positive versus -negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long-term follow-up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon-free HCV therapies this should not be a barrier to LuTx. PMID- 26998740 TI - Contrast-enhancing tumor growth dynamics of preoperative, treatment-naive human glioblastoma. AB - BACKGROUND: Little is known about the natural growth characteristics of untreated glioblastoma before surgical or therapeutic intervention, because patients are rapidly treated after preliminary radiographic diagnosis. Understanding the growth characteristics of uninhibited human glioblastoma may be useful for characterizing changes in response to therapy. Thus, the objective of the current study was to explore tumor growth dynamics in a cohort of patients with untreated glioblastoma before surgical or therapeutic intervention. METHODS: Ninety-five patients with glioblastoma who had measurable enhancing disease on >2 magnetic resonance imaging scans before surgery were identified. Tumor growth rates were quantified in 4 different ways (the percentage change per day, the absolute rate of change per day, the estimated volumetric doubling time, and the radial expansion rate) using 3 different approaches (bidirectional product, enhancing disease, and total lesion volume). RESULTS: The median volumetric doubling time was 21.1 days, the percentage change in tumor volume was 2.1% per day, and the rate of change in total lesion volume was 0.18 cc per day. The length of follow up between magnetic resonance imaging examinations should be >28 days to detect progressive disease with high specificity. Small initial tumor sizes (<3 cm in greatest dimension) are biased toward a large percentage change at follow-up. CONCLUSIONS: Presurgical, treatment-naive glioblastoma growth dynamics can be estimated in a variety of ways with similar results. The percentage changes in tumor size and volume depend on baseline tumor size and the time interval between scans. Cancer 2016;122:1718-27. (c) 2016 American Cancer Society. PMID- 26998742 TI - In vitro and in vivo comparative study of cosmetic ingredients Coffee silverskin and hyaluronic acid. PMID- 26998741 TI - Novel p53 target gene FUCA1 encodes a fucosidase and regulates growth and survival of cancer cells. AB - The tumor suppressor p53 functions by inducing the transcription of a collection of target genes. We previously attempted to identify p53 target genes by microarray expression and ChIP-sequencing analyses. In this study, we describe a novel p53 target gene, FUCA1, which encodes a fucosidase. Although fucosidase, alpha-l-1 (FUCA1) has been reported to be a lysosomal protein, we detected it outside of lysosomes and observed that its activity is highest at physiological pH. As there is a reported association between fucosylation and tumorigenesis, we investigated the potential role of FUCA1 in cancer. We found that overexpression of FUCA1, but not a mutant defective in enzyme activity, suppressed the growth of cancer cells and induced cell death. Furthermore, we showed that FUCA1 reduced fucosylation and activation of epidermal growth factor receptor, and concomitantly suppressed epidermal growth factor signaling pathways. FUCA1 loss of-function mutations are found in several cancers, its expression is reduced in cancers of the large intestine, and low FUCA1 expression is associated with poorer prognosis in several cancers. These results show that protein defucosylation mediated by FUCA1 is involved in tumor suppression. PMID- 26998744 TI - Comparison of Unit-Level Patient Turnover Measures in Acute Care Hospital Settings. AB - High patient turnover is a critical factor increasing nursing workload. Despite the growing number of studies on patient turnover, no consensus about how to measure turnover has been achieved. This study was designed to assess the correlation among patient turnover measures commonly used in recent studies and to examine the degree of agreement among the measures for classifying units with different levels of patient turnover. Using unit-level data collected for this study from 292 units in 88 hospitals participating in the National Database of Nursing Quality Indicators(r), we compared four patient turnover measures: the inverse of length of stay (1/LOS), admissions, discharges, and transfers per daily census (ADTC), ADTC with short-stay adjustment, and the number of ADTs and short-stay patients divided by the total number of treated patients, or Unit Activity Index (UAI). We assessed the measures' agreement on turnover quartile classifications, using percent agreement and Cohen's kappa statistic (weighted and unweighted). Pearson correlation coefficients also were calculated. ADTC with or without adjustment for short-stay patients had high correlations and substantial agreement with the measure of 1/LOS (kappa = .62 to .91; r = .90 to .95). The UAI measure required data less commonly collected by participating hospital units and showed only moderate correlations and fair agreement with the other measures (kappa = .23 to .39; r = .41 to .45). The UAI may not be comparable and interchangeable with other patient turnover measures when data are obtained from multiple units and hospitals. (c) 2016 Wiley Periodicals, Inc. PMID- 26998743 TI - [Detection of bocavirus in 4-week-old puppies with acute diarrhea]. AB - Two 4-month-old female Doberman puppies were presented with clinical signs of acute diarrhea and emesis. They also showed sneezing and nasal discharge. The clinical presentation and neutropenia were suggestive of a parvovirus infection. The puppies were hospitalized for several days and treated symptomatically. Fecal samples tested negative for parasites. Virological examination of feces using polymerase chain reaction (PCR) and immune electron microscopy failed to confirm a parvovirus infection. With a recently developed PCR, bocavirus could be identified, thus making an infection with this virus a possible diagnosis. This case report presents a less well-known viral puppy disease and its successful therapy. PMID- 26998745 TI - Protocolized versus non-protocolized weaning for reducing the duration of invasive mechanical ventilation in newborn infants. AB - BACKGROUND: Mechanical ventilation is a life-saving intervention for critically ill newborn infants with respiratory failure admitted to a neonatal intensive care unit (NICU). Ventilating newborn infants can be challenging due to small tidal volumes, high breathing frequencies, and the use of uncuffed endotracheal tubes. Mechanical ventilation has several short-term, as well as long-term complications. To prevent complications, weaning from the ventilator is started as soon as possible. Weaning aims to support the transfer from full mechanical ventilation support to spontaneous breathing activity. OBJECTIVES: To assess the efficacy of protocolized versus non-protocolized ventilator weaning for newborn infants in reducing the duration of invasive mechanical ventilation, the duration of weaning, and shortening the NICU and hospital length of stay. To determine efficacy in predefined subgroups including: gestational age and birth weight; type of protocol; and type of protocol delivery. To establish whether protocolized weaning is safe and clinically effective in reducing the duration of mechanical ventilation without increasing the risk of adverse events. SEARCH METHODS: We searched the Cochrane Central Register of Controlled trials (CENTRAL; the Cochrane Library; 2015, Issue 7); MEDLINE In-Process and other Non-Indexed Citations and OVID MEDLINE (1950 to 31 July 2015); CINAHL (1982 to 31 July 2015); EMBASE (1988 to 31 July 2015); and Web of Science (1990 to 15 July 2015). We did not restrict language of publication. We contacted authors of studies with a subgroup of newborn infants in their study, and experts in the field regarding this subject. In addition, we searched abstracts from conference proceedings, theses, dissertations, and reference lists of all identified studies for further relevant studies. SELECTION CRITERIA: Randomized, quasi-randomized or cluster randomized controlled trials that compared protocolized with non-protocolized ventilator weaning practices in newborn infants with a gestational age of 24 weeks or more, who were enrolled in the study before the postnatal age of 28 completed days after the expected date of birth. DATA COLLECTION AND ANALYSIS: Four authors, in pairs, independently reviewed titles and abstracts identified by electronic searches. We retrieved full-text versions of potentially relevant studies. MAIN RESULTS: Our search yielded 1752 records. We removed duplicates (1062) and irrelevant studies (843). We did not find any randomized, quasi randomized or cluster-randomized controlled trials conducted on weaning from mechanical ventilation in newborn infants. Two randomized controlled trials met the inclusion criteria on type of study and type of intervention, but only included a proportion of newborns. The study authors could not provide data needed for subgroup analysis; we excluded both studies. AUTHORS' CONCLUSIONS: Based on the results of this review, there is no evidence to support or refute the superiority or inferiority of weaning by protocol over non-protocol weaning on duration of invasive mechanical ventilation in newborn infants. PMID- 26998746 TI - Condensin in Chromatid Cohesion and Segregation. AB - After replication of genomic DNA during the S phase, 2 chromatids hold together longitudinally. When cells enter mitosis, the paired sister chromatids start to condense and then segregate into individual chromatids except for the centromeric region. Upon attachment of microtubules to the kinetochore, subsequent pulling of the 2 sister chromatids by the spindles towards opposite poles results in 2 completely separated chromatids. Besides more than 100 kinds of kinetochore proteins, several key proteins such as cohesin, separase, shugoshin, and condensin contribute to chromatid cohesion and segregation. Among these proteins, condensin, a protein complex composed of 5 subunits discovered 2 decades ago, has been extensively studied in terms of the maintenance of chromosome morphology as its major function. Recent studies on condensin uncovered its role in chromatid cohesion and segregation, which will be reviewed in this article. PMID- 26998747 TI - Evaluation of Hearing Function by Auditory Brainstem Response in Newborn Patients with Hydrocephalus before and after Ventriculoperitoneal Shunt Surgery. AB - BACKGROUND/AIM: There is currently no objective evaluation of hearing in patients with hydrocephalus (HCP), and we could not find any study in the literature comprising a sufficient number of patients with a high level of scientific evidence. In the current study, we used the auditory brainstem response (ABR) test to assess whether hearing function in patients with HCP is altered after ventriculoperitoneal shunt surgery. METHODS: In total, 20 newborn patients with HCP (13 female, 7 male) were enrolled in this study. For each patient, ABR testing was performed at three time points: 1 day prior to the operation and on days 7 and 90 after the operation. ABRs using click stimuli of 90, 70, 50 and 30 dB nHL (normal hearing level) were achieved for V-wave latency, and I-III and I IV interpeak latencies for both ears were recorded. Variance analysis for parametric data and Tukey's post hoc honest significant difference test were used to demonstrate the relationship between the results obtained from the different recording periods. Results were considered significant at p < 0.05, and 95% confidence intervals were calculated. RESULTS: The mean values of the ABR tests were compared between the pre- and postoperative results, which showed an increase (faster transmission) of nerve conduction velocity of 0.2 ms. The results were not statistically significant for 50 and 90 dB (p > 0.05) but were significant for 30 and 70 dB (p < 0.05). CONCLUSION: Diagnosis in hydrocephalic patients is important not only for the treatment but also for the prevention of HCP-associated complications. Early treatment appears to be promising in terms of auditory benefit. Prompt diagnosis and treatment are therefore essential as soon as possible. PMID- 26998749 TI - C. elegans Demonstrates Distinct Behaviors within a Fixed and Uniform Electric Field. AB - C. elegans will orient and travel in a straight uninterrupted path directly towards the negative pole of a DC electric field. We have sought to understand the strategy worms use to navigate to the negative pole in a uniform electric field that is fixed in both direction and magnitude. We examined this behavior by quantifying three aspects of electrotaxis behavior in response to different applied field strengths: the mean approach trajectory angles of the animals' tracks, turning behavior (pirouettes) and average population speeds. We determined that C. elegans align directly to the negative pole of an electric field at sub-preferred field strength and alter approach trajectories at higher field strengths to maintain taxis within a preferred range we have calculated to be ~ 5V/cm. We sought to identify the sensory neurons responsible for the animals' tracking to a preferred field strength. eat-4 mutant animals defective in glutamatergic signaling of the amphid sensory neurons are severely electrotaxis defective and ceh-36 mutant animals, which are defective in the terminal differentiation of two types of sensory neurons, AWC and ASE, are partially defective in electrotaxis. To further elucidate the role of the AWC neurons, we examined the role of each of the pair of AWC neurons (AWCOFF and AWCON), which are functionally asymmetric and express different genes. nsy-5/inx 19 mutant animals, which express both neurons as AWCOFF, are severely impaired in electrotaxis behavior while nsy-1 mutants, which express both neurons as AWCON, are able to differentiate field strengths required for navigation to a specific field strength within an electric field. We also tested a strain with targeted genetic ablation of AWC neurons and found that these animals showed only slight disruption of directionality and turning behavior. These results suggest a role for AWC neurons in which complete loss of function is less disruptive than loss of functional asymmetry in electrotaxis behavior within a uniform fixed field. PMID- 26998748 TI - Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury. AB - Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation. Moreover, TBI deregulates Ca(2+) -homeostasis triggering p25 production. The protein kinase Cdk5 is aberrantly activated by p25 leading to phosphorylation of substrates including tau and Rb protein. Loss of Cdk5 attenuates TBI lesion size, indicating that Cdk5 is a critical player in TBI pathogenesis and thus may be a suitable therapeutic target for TBI. PMID- 26998751 TI - Exploring Geographic Variability in Cancer Prevalence in Eastern Morocco: A Retrospective Study over Eight Years. AB - BACKGROUND: Malignant diseases have been believed to be more common in some areas of Eastern Morocco, but until now, cancer patterns have not been reported for this region. In this paper we present for the first time the cancer prevalence analysis in Eastern Morocco. METHODS: Cross-sectional study carried out among all patients diagnosed and/or treated with cancer at the Hassan II Regional Oncology Center (ROC) since it was established in October 2005 until December 2012. The ROC is the only hospital specialized in cancer care in Eastern Morocco. RESULTS: A total of 8,508 cases of cancer were registered among residents in Eastern Morocco, with a female to male ratio of 2.1. The mean age at diagnosis was 53.9 +/- 15.2 years (median age = 53 years). Thus, unlike in Western countries, cancer in Eastern Morocco afflicts younger population. The areas of Eastern Morocco did not differ significantly by mean age at diagnosis (p = 0.061). However, these regions differed significantly by sex ratio (p < 0.001). The highest sex ratio was observed in Figuig, with a female to male ratio of 3.1 (75.4% of the registered case were females), followed respectively by Taourirt, Oujda-Angad, Berkane, Nador-Driouch and Jerada. Clear variation in the distribution of cancer types between areas of Eastern Morocco was observed, both in males and females (p < 0.001). Furthermore, the areas of Eastern Morocco differed significantly by cancer prevalence (p < 0.001). The highest age-standardized five-year prevalence proportion was observed in Oujda-Angad with 420.2 per 100,000, followed respectively by Berkane (311.4), Jerada (287.8), Taourirt (269.3), Nador-Driouch (213.6) and Figuig (194.4). Trends in the five-year prevalence proportions decreased in Oujda-Angad, Berkane and Jerada throughout the study period, while an increasing trend was observed in Nador-Driouch, Taourirt and Figuig. CONCLUSIONS: For the first time, our study presents the pattern and distribution of diagnosed cancers in Eastern Morocco. Our study illustrates substantial differences in cancer patterns between areas of Eastern Morocco. These findings are important for cancer control and highlight the need to develop program aiming at controlling and preventing the spread of major cancer sites in Eastern Morocco, particularly in areas with increased cancer prevalence rates. PMID- 26998750 TI - The Circular RNA Cdr1as Promotes Myocardial Infarction by Mediating the Regulation of miR-7a on Its Target Genes Expression. AB - OBJECTIVES: Recent studies have demonstrated the role of Cdr1as (or CiRS-7), one of the well-identified circular RNAs (circRNAs), as a miR-7a/b sponge or inhibitor in brain tissues or islet cells. This study aimed to investigate the presence of Cdr1as/miR-7a pathway in cardiomyocytes, and explore the mechanism underlying the function of miR-7a in protecting against myocardial infarction (MI)-induced apoptosis. METHODS: Mouse MI injury model was established and evaluated by infarct size determination. Real-time PCR was performed to quantify the expression of Cdr1as and miR-7a in cardiomyocytes. Cell apoptosis was determined by caspase-3 activity analysis and flow cytometry assays with Annexin V/PI staining. Transfection of Cdr1as overexpressing plasmid and miR-7a mimic were conducted for gain-of-function studies. Luciferase reporter assay and western blot analysis were performed to verity potential miR-7a targets. RESULTS: Cdr1as and miR-7a were both upregulated in MI mice with increased cardiac infarct size, or cardiomyocytes under hypoxia treatment. Cdr1as overexpression in MCM cells promoted cell apoptosis, but was then reversed by miR-7a overexpression. The SP1 was identified as a new miR-7a target, in line with previously identified PARP, while miR-7a-induced decrease of cell apoptosis under hypoxia treatment was proven to be inhibited by PARP-SP1 overexpression. Moreover, Cdr1as overexpression in vivo increased cardiac infarct size with upregulated expression of PARP and SP1, while miR-7a overexpression reversed these changes. CONCLUSIONS: Cdr1as also functioned as a powerful miR-7a sponge in myocardial cells, and showed regulation on the protective role of miR-7a in MI injury, involving the function of miR-7a targets, PARP and SP1. PMID- 26998752 TI - Hepcidin resistance in dysmetabolic iron overload. AB - BACKGROUND & AIMS: Dysmetabolic iron overload syndrome (DIOS) is a frequent condition predisposing to metabolic, cardiovascular and hepatic damage, whose pathogenesis remains poorly defined. Aim of this study was to characterize iron metabolism in DIOS. METHODS: We evaluated 18 patients with DIOS, compared to 18 with nonalcoholic fatty liver and 23 healthy individuals with normal iron status, and 10 patients with hereditary haemochromatosis by a 24-h oral iron tolerance test with hepcidin measurement and iron metabolism modelling under normal iron stores. RESULTS: Dysmetabolic iron overload syndrome patients had higher peak transferrin saturation and area under the-curve of transferrin saturation than subjects with normal iron status, but lower values than haemochromatosis patients (P < 0.05 for all). Conversely, they had higher peak circulating hepcidin levels and area under the curve of hepcidin than the other groups (P < 0.05 for all). This was independent age, sex, haemoglobin, ferritin, and transferrin saturation levels (P = 0.0002). Hepcidin increase in response to the rise in transferrin saturation (hepcidin release index) was not impaired in DIOS patients. Viceversa, the ability of the hepcidin spike to control the rise in transferrin saturation at the beginning of the test (hepcidin resistance index) was impaired in DIOS (P = 0.0002). In DIOS patients, the hepcidin resistance index was correlated with ferritin levels at diagnosis (P = 0.016). CONCLUSIONS: Dysmetabolic iron overload syndrome is associated with a subtle impairment in the ability of the iron hormone hepcidin to restrain iron absorption following an iron challenge, suggesting a hepcidin resistance state. Further studies are required to better characterize the molecular mechanism underpinning this new iron metabolism alteration. PMID- 26998754 TI - Catalyst-Free Three-Component Tandem CDC Cyclization: Convenient Access to Isoindolinones from Aromatic Acid, Amides, and DMSO by a Pummerer-Type Rearrangement. AB - A catalyst-free multicomponent CDC reaction is rarely reported, especially for the intermolecular tandem CDC cyclization, which represents an important strategy for constructing cyclic compounds. Herein, a three-component tandem CDC cyclization by a Pummerer-type rearrangement to afford biologically relevant isoindolinones from aromatic acids, amides, and DMSO, is described. This intermolecular tandem reaction undergoes a C(sp(2) )-H/C(sp(3) )-H cross dehydrogenative coupling, C-N bond formation, and intramolecular amidation. A notable feature of this novel protocol is avoiding a catalyst and additive (apart from oxidant). PMID- 26998753 TI - In kidney transplant recipients with BK polyomavirus infection, early BK nephropathy, microvascular inflammation, and serum creatinine are risk factors for graft loss. AB - BACKGROUND: Little information is available on the risk factors for graft loss in kidney transplant recipients with BK polyomavirus (BKPyV) nephropathy (BKVN) in the presence or absence of antibody-mediated rejection (AMR). METHODS: We examined the risk factors for graft loss in consecutive kidney allograft recipients with biopsy-confirmed BKVN, with or without concomitant AMR. RESULTS: A total of 1904 kidney transplants were performed at our institution during 2005 2011. Of these, 330 (17.33%) were diagnosed with BKPyV viremia, and 69 were diagnosed with BKVN (3.6%). Eleven patients had a concomitant diagnosis of AMR. Patients with AMR were characterized by significantly higher peak panel-reactive antibody, retransplant rates, and desensitization preconditioning at the time of transplantation, as well as microvascular inflammation (MVI = glomerulitis + peritubular capillaritis), C4d score, and donor-specific antibody at the time of diagnosis (P <= 0.01). Treatment with plasma exchange, intravenous immunoglobulin, and cidofovir was more prevalent in this group (P <= 0.02). Univariate analyses assessing the risk factors for graft loss in all patients with BKVN, identified an independent association of African-American race, deceased-donor transplantation, serum creatinine (Scr), MVI, and early disease (BKVN within 6 months of transplant) with poor outcomes. Multivariate analyses retained only 3 variables: Scr >2 mg/dL (hazard ratio [HR] = 4.3, 95% confidence interval [CI] 1.9-9.7, P = 0.0004), early BKVN (HR = 2.7, 95% CI 1.3-5.3, P = 0.004), and MVI (HR = 1.8, 95% CI 1.2-2.8, P = 0.008). CONCLUSIONS: These observations suggest that, in patients with BK infection, early BKVN, Scr >2, and MVI are predictors of poor outcomes. Further studies are needed to determine effective treatment strategies for BKVN, with or without AMR. PMID- 26998755 TI - Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs. AB - Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete's urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as 'T equivalent' concentrations by comparison to a T dose response curve. The T equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 +/- 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact. PMID- 26998756 TI - Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease. AB - OBJECTIVE: To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD). METHODS: The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin. RESULTS: The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 +/- 2.95) than in those without (13.56 +/- 3.09), and much higher than in controls (8.79+/ 2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05. CONCLUSIONS: Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD. PMID- 26998757 TI - Revealing the Pharmacophore of Ipomoeassin F through Molecular Editing. AB - Ipomoeassin F, the flagship congener of a resin glycoside family exhibited single digit nanomolar IC50 values against several cancer cell lines. To facilitate drug discovery based on this unique yet underexplored natural product, we performed the most sophisticated SAR studies of ipomoeassin F to date, which not only greatly bettered our understanding of its pharmacophore but also led to the discovery of two new derivatives (3 and 27) with similar potency but improved synthetic profile. The work presented here opens new avenues toward harnessing the medicinal potential of the ipomoeassin family of glycolipids in the future. PMID- 26998759 TI - Correction: Identification of Androgen Receptor Splice Variants in the Pten Deficient Murine Prostate Cancer Model. PMID- 26998758 TI - Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach. AB - BACKGROUND: Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. MATERIALS & METHODS: In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. RESULTS: Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. CONCLUSION: These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects. PMID- 26998760 TI - Early Transcriptome Signatures from Immunized Mouse Dendritic Cells Predict Late Vaccine-Induced T-Cell Responses. AB - Systems biology offers promising approaches for identifying response-specific signatures to vaccination and assessing their predictive value. Here, we designed a modelling strategy aiming to predict the quality of late T-cell responses after vaccination from early transcriptome analysis of dendritic cells. Using standardized staining with tetramer, we first quantified antigen-specific T-cell expansion 5 to 10 days after vaccination with one of a set of 41 different vaccine vectors all expressing the same antigen. Hierarchical clustering of the responses defined sets of high and low T cell response inducers. We then compared these responses with the transcriptome of splenic dendritic cells obtained 6 hours after vaccination with the same vectors and produced a random forest model capable of predicting the quality of the later antigen-specific T-cell expansion. The model also successfully predicted vector classification as low or strong T cell response inducers of a novel set of vaccine vectors, based on the early transcriptome results obtained from spleen dendritic cells, whole spleen and even peripheral blood mononuclear cells. Finally, our model developed with mouse datasets also accurately predicted vaccine efficacy from literature-mined human datasets. PMID- 26998761 TI - Initiation of T cell signaling by CD45 segregation at 'close contacts'. AB - It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts. PMID- 26998762 TI - A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity. AB - 14-3-3 proteins regulate biological processes by binding to phosphorylated serine or phosphorylated threonine motifs of cellular proteins. Among the 14-3-3 proteins, 14-3-3E serves a crucial function in antiviral immunity by mediating the cytosol-to-mitochondrial membrane translocation of the pathogen sensor RIG-I. Here we found that the NS3 protein of dengue virus (DV) bound to 14-3-3E and prevented translocation of RIG-I to the adaptor MAVS and thereby blocked antiviral signaling. Intriguingly, a highly conserved phosphomimetic RxEP motif in NS3 was essential for the binding of 14-3-3E. A recombinant mutant DV deficient in binding to 14-3-3E showed impairment in antagonism of RIG-I and elicited a markedly augmented innate immune response and enhanced T cell activation. Our work reveals a novel phosphomimetic-based mechanism for viral antagonism of 14-3-3-mediated immunity, which might guide the rational design of therapeutics. PMID- 26998765 TI - Iodine supplementation in pregnancy - is it time? AB - Iodine is essential for the synthesis of thyroid hormone and optimal foetal neurological development. Pregnant women living in borderline or moderate-severe iodine deficient areas are at particularly high risk of being iodine deficient, and this may have important clinical consequences, particularly for the neurocognitive development of the offspring. It is a substantial problem and many countries including the United Kingdom are mild-moderately iodine deficient. Although the detrimental effects of severe iodine deficiency are well recognized, the benefits of correcting mild-to-moderate iodine deficiency are unclear due to a lack of randomized controlled trials in this area. However, observational data increasingly indicate that there may be substantial health and economic benefits from correcting iodine deficiency in pregnancy. There is now a growing trend from learned societies that iodine supplementation should be utilized in pregnancy in countries with mild-to-moderate iodine deficiency. The dose of iodine supplement needs to reflect local iodine status and iodization policies and will need careful monitoring at the population level to ensure doses to prevent under/excess dosing which would undermine the potential benefits. National tailored guidance is therefore essential. PMID- 26998767 TI - Overview of the 2015 ICS Consensus Conference. AB - PURPOSE: The AMS800TM device is considered to be the "gold-standard" when male incontinence surgical treatment is contemplated. Despite 40 years of experience, it is still a specialized procedure with a number of challenges. Here, we present the recommendations issued from the AUS Consensus Group, regarding indications, management and follow-up AMS800TM implantation or revision. MATERIALS AND METHODS: Under ICS auspices, an expert panel met on July 10, 2015 in Chicago, IL, USA in an attempt to reach a consensus on diverse issues related to the AMS800TM device. Participants were selected by the two co-chairs on the basis of their practice in a University hospital and their experience: number of implanted AUSs according to AMS (American Medical System Holdings Inc., Minnetonka, MN) records and/or major published articles. Topics listed were the result of a pre-meeting email brainstorming by all participants. The co-chairs distributed topics randomly to all participants, who then had to propose a statement on each topic for approval by the conference after a short evidence-based presentation, when possible. RESULTS: The present recommendations, based on the most recent and relevant data available in literature as well as expert opinions, successively address multiple specific and problematic issues associated with the AMS800TM trough a 6-chapter structure: pre-operative assessment, pre operative challenges, implantation technique, post-operative care, trouble-shooting, and special populations. CONCLUSION: These guidelines undoubtedly constitute a reference document, which will help urologists to carefully select patients and apply the most adapted management to implantation, follow-up and trouble-shooting of the AMS800TM. Neurourol. Urodynam. 35:437-443, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26998763 TI - T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis. AB - Interleukin 1beta (IL-1beta) is critical for the in vivo survival, expansion and effector function of IL-17-producing helper T (T(H)17) cells during autoimmune responses, including experimental autoimmune encephalomyelitis (EAE). However, the spatiotemporal role and cellular source of IL-1beta during EAE pathogenesis are poorly defined. In the present study, we uncovered a T cell-intrinsic inflammasome that drives IL-1beta production during T(H)17-mediated EAE pathogenesis. Activation of T cell antigen receptors induced expression of pro-IL 1beta, whereas ATP stimulation triggered T cell production of IL-1beta via ASC NLRP3-dependent caspase-8 activation. IL-1R was detected on T(H)17 cells but not on type 1 helper T (T(H)1) cells, and ATP-treated T(H)17 cells showed enhanced survival compared with ATP-treated T(H)1 cells, suggesting autocrine action of T(H)17-derived IL-1beta. Together these data reveal a critical role for IL-1beta produced by a T(H)17 cell-intrinsic ASC-NLRP3-caspase-8 inflammasome during inflammation of the central nervous system. PMID- 26998768 TI - Attitudes of Turkish Nursing Students Related to Ageism. AB - BACKGROUND: The sociocultural structure of society, changes in attitude and behaviors, and individual and social perspectives on aging all affect the nature of services that are offered to elderly people. "Ageism" is one of the problems that has an impact on the level and quality of service that is provided to the older adults. PURPOSE: This study was undertaken to examine the attitudes of Turkish undergraduate nursing students toward aging. METHODS: A cross-sectional survey was given to 495 nursing students in four universities in Turkey. A questionnaire developed from the related literature and the Ageism Attitude Scale were used to collect data, which was analyzed using standard descriptive statistical methods. RESULTS: The variables of school year, age, cohabitation with an elderly person (yes/no), prior experience with the older adults (yes/no), and willingness to work with the older adults after graduation all significantly influenced the attitudes of participants toward aging (p < .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results from the Ageism Attitude Scale revealed that the participants held a generally positive attitude toward aging. It is of great importance to include more lessons on the older adults and the aging process and to increase activities to develop awareness of ageism, to help students develop positive attitudes and perspectives toward the care of the older adults. Because experience caring for the older adults is important in developing a positive attitude toward the older adults, arranging relevant clinical practice, especially at institutions with an elderly population, may be an effective approach to strengthening the communication and experiences of nursing students. PMID- 26998764 TI - Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease. AB - The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity. PMID- 26998769 TI - The Perceptions and Expectations Toward the Social Responsibility of Hospitals and Organizational Commitment of Nursing Staff. AB - BACKGROUND: The labor rights of medical workers in hospitals in Taiwan have been a key issue of discussion and controversy in recent years. Generally, poor work conditions and manpower shortages in hospitals have resulted in a vicious circle of severely overworked medical and healthcare staff and chronically low staffing and retention rates. PURPOSE: This study employed corporate social responsibility as the conceptual framework of the social responsibility of hospitals to examine the perceptions and expectations of nurses toward the social responsibility practices of the hospital where they serve and to explore the relationship between these perceptions and organizational commitment (OC). METHODS: The participants were all nurses who were employed by one medical group in southern Taiwan. Two hundred forty anonymous questionnaires, which included scales that were designed to measure the social responsibility of hospitals and OC, were distributed. Two hundred twenty-seven valid questionnaires were returned. Exploratory factor analysis was used to validate the dimension of the social responsibility of hospitals, and hierarchical multiregression analyses were used to verify the relationship between the perceptions of nurses with regard to the social responsibility practices of the hospital where nurses serve and OC. RESULTS: There were considerable differences between participants' perceptions and expectations toward the social responsibility of hospitals. The nurses with high perceptions toward the social responsibility practices of the hospital where they serve tended to have relatively high OC. Senior nurses who had high perceptions of the legal and rational, ethical, and economic dimensions of the social responsibility practices of the hospital where they serve exhibited relatively strong affective commitment. Nurses in junior positions who had high perceptions of the practices of ethical responsibilities exhibited relatively strong continuance commitment. Senior nurses who had high perceptions of the legal and rational, ethical, and discretionary dimensions of the social responsibility practices of the hospital where they serve exhibited relatively strong normative commitment. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: A friendly and humane work environment in hospital settings facilitates the implementation of social responsibility, which has been shown to foster higher levels of organizational identification and job performance among nurses and other hospital employees. PMID- 26998766 TI - Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment-to-target strategy. AB - OBJECTIVE: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early RA, achieved with treat-to-target management in clinical practice. METHODS: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by DAS28-CRP < 2.6. Twelve-month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on US of 26 joints (total PDA score = 0 or ?1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes. RESULTS: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Among patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42, 44 and 40%, respectively; absent/minimal PDA was detected in 62, 66 and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of OA predicted absence of PDA, and lower total baseline PDA predicted absent/minimal PDA. CONCLUSION: DAS28-CRP remission and absence of PDA were observed in almost half of the patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target. PMID- 26998771 TI - A Comparison of Life Stress and Depressive Symptoms in Pregnant Taiwanese and Immigrant Women. AB - BACKGROUND: An increasing number of women from other countries, mostly Mainland China and Southeast Asia, are marrying Taiwanese husbands and settling in Taiwan. Immigration, marriage abroad, and pregnancy may be stressful and adversely affect maternal health. Relatively little research has compared the life stress and depressive symptoms of pregnant women of different ethnic groups living in nonmetropolitan areas in Taiwan. PURPOSE: This study investigates the levels of life stress and depressive symptoms in pregnant Taiwanese women and Vietnamese "foreign brides" currently living in southern Taiwan. METHODS: Eligible women in their last trimester of pregnancy who attended their local antenatal clinic were recruited for the study. Participants completed standardized measures, including the Difficult Life Circumstances Scale, Social Support APGAR Scale, and Edinburgh Postnatal Depression Scale. RESULTS: Two hundred thirty-six Taiwanese women and 44 Vietnamese women participated. Major life difficulties for both groups of women were related to their marital relationship, housing, or health problems. Taiwanese participants reported perceiving financial strain more often than their Vietnamese peers, whereas Vietnamese participants reported perceiving greater concerns regarding their children's development and about recent physical abuse than their Taiwanese peers. Furthermore, the Vietnamese participants reported less social support and higher rates of antenatal depression than Taiwanese participants. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Clinical nurses and midwives should be sensitive to the particular difficulties and insufficient social support faced by pregnant women from different backgrounds in Taiwan. Women from foreign countries or those under unique challenging circumstances may face a particular risk of adverse outcomes. Identifying stresses informs the development of effective nursing interventions and support activities for new mothers and their families. PMID- 26998775 TI - Depression and Its Associated Factors Among Rural Diabetic Residents. AB - BACKGROUND: Type 2 diabetes is a huge burden both for individuals and society as a whole. Although depression has been negatively associated with ideal glycemic control, little is known about the prevalence of depression or its associated factors among rural Taiwanese adults with Type 2 diabetes mellitus (type2 DM). PURPOSE: The purposes of this study were to investigate the prevalence of depression in rural-dwelling sufferers of type2 DM and to highlight the relationships between their depression status and health promoting behaviors such as physical activity, keeping active in life, sleep sufficiency, and adopting a diabetic diet. METHODS: A cross-sectional, correlational design was used to recruit 696 participants from local healthcare centers in rural areas of Chiayi County, Taiwan. Data were collected from March 30, 2010, to August 30, 2012. The Chinese version of the Geriatric Depression Scale and its associated physiological biomarkers were used as screening tools. Logistic regression was used to identify the factors that were associated with depression status. RESULTS: The prevalence of depression in this study was 16.8%. Factors found to be associated with depression included being female, having a low level of education, receiving reduced family support, having little physical activity, failing to follow a diabetic diet, frequent inactivity, and having insufficient sleep. There were no significant differences in the physiological indicators between the depressive and nondepressive groups. After controlling for confounding factors, a logistic regression model showed that depression status was associated with a lack of sleep (OR = 2.85, p < .001), less frequent exercise (OR = 2.67, p < .001), and frequent inactivity (OR = 2.35, p = .001). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study showed that the prevalence of depression among adults with type2 DM living in rural areas is relatively high. From the perspective of health promotion, future research should focus on how to improve quality of sleep by enhancing daily physical activity and on investigating the effect of promoting a more active lifestyle among those at risk on depression. PMID- 26998777 TI - Current insight into pathophysiology of gastroduodenal ulcers: Why do only some ulcers perforate? PMID- 26998776 TI - Arsenic Methylation in Arabidopsis thaliana Expressing an Algal Arsenite Methyltransferase Gene Increases Arsenic Phytotoxicity. AB - Arsenic (As) contamination in soil can lead to elevated transfer of As to the food chain. One potential mitigation strategy is to genetically engineer plants to enable them to transform inorganic As to methylated and volatile As species. In this study, we genetically engineered two ecotypes of Arabidopsis thaliana with the arsenite (As(III)) S-adenosylmethyltransferase (arsM) gene from the eukaryotic alga Chlamydomonas reinhardtii. The transgenic A. thaliana plants gained a strong ability to methylate As, converting most of the inorganic As into dimethylarsenate [DMA(V)] in the shoots. Small amounts of volatile As were detected from the transgenic plants. However, the transgenic plants became more sensitive to As(III) in the medium, suggesting that DMA(V) is more phytotoxic than inorganic As. The study demonstrates a negative consequence of engineered As methylation in plants and points to a need for arsM genes with a strong ability to methylate As to volatile species. PMID- 26998778 TI - Brain hypoxia is exacerbated in hypobaria during aeromedical evacuation in swine with traumatic brain injury. AB - BACKGROUND: There is inadequate information on the physiologic effects of aeromedical evacuation on wounded war fighters with traumatic brain injury (TBI). At altitudes of 8,000 ft, the inspired oxygen is lower than standard sea level values. In troops experiencing TBI, this reduced oxygen may worsen or cause secondary brain injury. We tested the hypothesis that the effects of prolonged aeromedical evacuation on critical neurophysiologic parameters (i.e., brain oxygenation [PbtO2]) of swine with a fluid percussion injury/TBI would be detrimental compared with ground (normobaric) transport. METHODS: Yorkshire swine underwent fluid percussion injury/TBI with pretransport stabilization before being randomized to a 4-hour aeromedical transport at simulated flight altitude of 8,000 ft (HYPO, n = 8) or normobaric ground transport (NORMO, n = 8). Physiologic measurements (i.e., PbtO2, cerebral perfusion pressure, intracranial pressure, regional cerebral blood flow, mean arterial blood pressure, and oxygen transport variables) were analyzed. RESULTS: Survival was equivalent between groups. Measurements were similar in both groups at all phases up to and including onset of flight. During the flight, PbtO2, cerebral perfusion pressure, and mean arterial blood pressure were significantly lower in the HYPO than in the NORMO group. At the end of flight, regional cerebral blood flow was lower in the HYPO than in the NORMO group. Other parameters such as intracranial pressure, cardiac output, and mean pulmonary artery pressure were not significantly different between the two groups. CONCLUSION: A 4-hour aeromedical evacuation at a simulated flight altitude of 8,000 ft caused a notable reduction in neurophysiologic parameters compared with normobaric conditions in this TBI swine model. Results suggest that hypobaric conditions exacerbate cerebral hypoxia and may worsen TBI in casualties already in critical condition. PMID- 26998779 TI - Cervical spine injuries in civilian victims of explosions: Should cervical collars be used? AB - BACKGROUND: Semirigid cervical collars (SRCCs) are routinely applied to victims of explosions as part of the prehospital trauma protocols. Previous studies have shown that the use of SRCC in penetrating injuries is not justified because of the scarcity of unstable cervical spine injuries and the risk of obscuring other neck injuries. Explosion can inflict injuries by fragments penetration, blast injury, blunt force, and burns. The purpose of the study was to determine the occurrence of cervical spine instability without irreversible neurologic deficit and other potentially life-threatening nonskeletal neck injuries among victims of explosions. The potential benefits and risks of SRCC application in explosion related injuries were evaluated. METHODS: This is a retrospective cohort study of all explosion civilian victims admitted to Israeli hospitals during the years 1998 to 2010. Data collection was based on the Israeli national trauma registry and the hospital records and included demographic, clinical, and radiologic details of all patients with documented cervical spine injuries. RESULTS: The cohort included 2,267 patients. All of them were secondary to terrorist attacks. SRCC was applied to all the patients at the scene. Nineteen patients (0.83%) had cervical spine fractures. Nine patients (0.088%) had unstable cervical spine injury. All but one had irreversible neurologic deficit on admission. A total of 151 patients (6.6%) had potentially life-threatening penetrating nonskeletal neck injuries. CONCLUSION: Unstable cervical spine injuries secondary to explosion are extremely rare. The majority of unstable cervical spine fractures were secondary to penetrating injuries, with irreversible neurologic deficits on admission. The application of SRCC did not seem to be of any benefit in these patients and might pose a risk of obscuring other neck injuries. We recommend that SRCC will not be used in the prehospital management of victims of explosions. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III. PMID- 26998780 TI - Not child's play: National estimates of microwave-related burn injuries among young children. AB - BACKGROUND: Previous studies have shown that children as young as 18 months can open a microwave and remove its contents causing sometimes severe scalds. Although this mechanism may be uniquely preventable by an engineering fix, no national estimate of this type of child burn injury has been reported. METHODS: We analyzed the Consumer Product Safety Commission's National Electronic Injury Surveillance System data on emergency department-treated microwave-related burn injuries from January 2002 through December 2012 in children aged 12 months to 4 years. Based on the narrative description of how the injury occurred, we defined a case as a burn with a mechanism of either definitely or probably involving a child himself or herself opening a microwave oven and accessing the heated contents. National estimates of cases and their characteristics were calculated. RESULTS: During the 11 years studied, an estimated 10,902 (95% confidence interval, 8,231-13,573) microwave-related burns occurred in children aged 12 months to 4 years. Of these, 7,274 (66.7%) (95% confidence interval, 5,135-9,413) were cases of children burned after accessing the contents of the microwave themselves. A total of 1,124 (15.5%) cases required hospitalization or transfer from the treating emergency department. Narratives for children as young as 12 months described the child himself or herself being able to access microwave contents. The most commonly burned body parts were the upper trunk (3,056 cases) and the face (1,039 cases). The most common scalding substances were water (2,863 cases), noodles (1,011 cases), and soup (931 cases). CONCLUSION: The majority of microwave-related burns in young children occur as a result of the child himself or herself accessing the microwave and removing the contents. More than 600 young children are treated in US emergency departments annually for such burns. Children as young as 12 months sustained burns caused by this mechanism of injury. These burns could be prevented with a redesign of microwaves to thwart young children from being able to open the microwave oven door. LEVEL OF EVIDENCE: Epidemiologic study, level III. PMID- 26998783 TI - Synthesis and Luminescence Properties of Novel Ce(3+)- and Eu(2+)-Doped Lanthanum Bromothiosilicate La3Br(SiS4)2 Phosphors for White LEDs. AB - Novel Ce(3+)- and Eu(2+)-doped lanthanum bromothiosilicate La3Br(SiS4)2:Ce(3+)and La3Br(SiS4)2:Eu(2+) phosphors were prepared by solid-state reaction in an evacuated and sealed quartz glass ampule. The La3Br(SiS4)2:Ce(3+) phosphor generates a cyan emission upon excitation at 375 nm, whereas the La3Br(SiS4)2:Eu(2+) phosphor could be excited with extremely broad range from UV to blue region (300 to 600 nm) and generates a reddish-orange broadband emission centered at 640 nm. In addition, thermal luminescence properties of La3Br(SiS4)2:Ce(3+)and La3Br(SiS4)2:Eu(2+) phosphors from 20 to 200 degrees C were investigated. The combination of a 450 nm blue InGaN-based LED chip with the red-emitting La3Br(SiS4)2:Eu(2+) phosphor, and green-emitting BOSE:Eu(2+) commercial phosphor produced a warm-white light with the CRI value of ~95 and the CCT of 5,120 K. Overall, these results show that the prepared phosphors may have potential applications in pc-WLED. PMID- 26998781 TI - Using social media for community consultation and public disclosure in exception from informed consent trials. AB - BACKGROUND: The US Food and Drug Administration and the Department of Health and Human Services outline regulations allowing an exception from informed consent (EFIC) for research conducted in an emergency setting. Acute care clinical trials using EFIC must include community consultation and public disclosure (CC/PD) activities. We describe our experience using social media to facilitate the CC/PD process in two trauma resuscitation clinical trials. METHODS: We conducted local CC/PD activities for two multicenter trauma clinical trials, Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) and Prehospital Tranexamic Acid Use for Traumatic Brain Injury (ROC-TXA). As part of the CC/PD process, we developed research study advertisements using the social media Web site Facebook. The Facebook advertisements directed users to a regional study Web site that contained trial information. We targeted the advertisements to specific demographic users, in specific geographic areas. We analyzed the data using descriptive statistics. RESULTS: During the study periods, the PROPPR Facebook advertisement was displayed 5,001,520 times (12 displays per target population) with 374 individuals selecting the advertisement. The ROC-TXA Facebook advertisement was displayed 3,806,448 times (8 per target population) with 790 individuals selecting the advertisement. Respondents to both Facebook advertisements were mostly male (52.6%), with the highest proportion between the ages 15 years and 24 years (28.2%). Collectively, 26.9% of individuals that clicked on the Facebook advertisement spent more than 3 minutes on the study Web site (3-49 minutes). Commonly accessed Web pages were "contact us" (PROPPR, 5.5%; ROC-TXA, 7.7%), "study-specific FAQs" (PROPPR, 2.4%; ROC-TXA, 6.7%), and "opt out of research" (PROPPR, 2.5%; ROC-TXA, 3.8%). Of 51 total individuals viewing the opt out of research information (PROPPR, 19; ROC-TXA, 32), time spent on that specific page was modest (PROPPR, 62 seconds; ROC-TXA, 55 seconds), with no individuals requesting to opt out of either study participation. CONCLUSIONS: In clinical trauma trials using EFIC, social media may provide a viable option for facilitating the CC/PD process. PMID- 26998784 TI - Modeling Source Water TOC Using Hydroclimate Variables and Local Polynomial Regression. AB - To control disinfection byproduct (DBP) formation in drinking water, an understanding of the source water total organic carbon (TOC) concentration variability can be critical. Previously, TOC concentrations in water treatment plant source waters have been modeled using streamflow data. However, the lack of streamflow data or unimpaired flow scenarios makes it difficult to model TOC. In addition, TOC variability under climate change further exacerbates the problem. Here we proposed a modeling approach based on local polynomial regression that uses climate, e.g. temperature, and land surface, e.g., soil moisture, variables as predictors of TOC concentration, obviating the need for streamflow. The local polynomial approach has the ability to capture non-Gaussian and nonlinear features that might be present in the relationships. The utility of the methodology is demonstrated using source water quality and climate data in three case study locations with surface source waters including river and reservoir sources. The models show good predictive skill in general at these locations, with lower skills at locations with the most anthropogenic influences in their streams. Source water TOC predictive models can provide water treatment utilities important information for making treatment decisions for DBP regulation compliance under future climate scenarios. PMID- 26998785 TI - Enhanced removal of trace Cr(VI) from neutral and alkaline aqueous solution by FeCo bimetallic nanoparticles. AB - The reactivity of zero valent iron (Fe(0)) for removing Cr(VI) is self-inhibiting under neutral and alkaline conditions, due to the precipitation of ferrous hydroxide on the surface of Fe(0). To overcome this difficulty, we incorporated a second metal (Co) into Fe(0) to form FeCo bimetallic nanoparticles (FeCo BNPs), which can achieve higher activity and significant improvement in the reaction kinetics for the removal of Cr(VI) compared with Fe(0). The FeCo BNPs were synthesized by a hydrothermal reduction method without using any templates. The characterization analysis indicated that the products were highly uniform in large scale with 120-140 nm size in diameter. The obtained FeCo BNPs exhibited a remarkable removal ability for Cr(VI) in the pH range of 5.3-10.0. Especially, FeCo BNPs were able to reduce trace Cr(VI) (1.0 mg L(-1), pH=7.5) down to about 0.025 mg L(-1) within 1h. XPS analysis confirmed that Cr(VI) was reduced to Cr(III) by FeCo BNPs, while Fe and Co was oxidized, implying a chemical reduction process. The enhanced removal of trace Cr(VI) could be originated from the introduction of Co, which not only served as a protecting agent against surface corrosion by galvanic cell effect, but also enhanced the efficient flow of electron transfer between iron and Cr(VI). All the results primarily imply that FeCo BNPs can be employed as high efficient material for wastewater treatment. PMID- 26998786 TI - Non-mulberry silk fibroin grafted poly (?-caprolactone)/nano hydroxyapatite nanofibrous scaffold for dual growth factor delivery to promote bone regeneration. AB - HYPOTHESIS: This study aims at developing biodegradable, mineralized, nanofibrous scaffolds for use in bone regeneration. Scaffolds are loaded with combinations of bone morphogenic protein-2 (rhBMP-2) and transforming growth factor beta (TGF beta) and evaluated in vitro for enhancement in osteoinductivity. EXPERIMENTS: Poly(?-caprolactone) (PCL) doped with different portions of nano-hydroxyapatite is electrospun into nanofibrous scaffolds. Non-mulberry silk fibroin (NSF) obtained from Antheraea mylitta is grafted by aminolysis onto them. Scaffolds prepared have three concentrations of nano-hydroxyapatite: 0% (NSF-PCL), 25% (NSF PCL/n25), and 50% (NSF-PCL/n50). Growth factor loading is carried out in three different combinations, solely rhBMP-2 (BN25), solely TGF-beta (TN25) and rhBMP 2+TGF-beta (T/B N25) via carbodiimide coupling. FINDINGS: NSF-PCL/n25 showed the best results in examination of mechanical properties, bioactivity, and cell viability. Hence only NSF-PCL/n25 is selected for loading growth factors and subsequent detailed in vitro experiments using MG-63 cell-line. Both growth factors show sustain release kinetics from the matrix. The T/B N25 scaffolds support cellular activity, proliferation, and triggering of bone-associated genes' expression better and promote earlier cell differentiation. Dual growth factor loaded NSF grafted electrospun PCL/nHAp scaffolds show promise for further development into a suitable scaffold for bone tissue engineering. PMID- 26998787 TI - Effects of shear-thinning fluids on residual oil formation in microfluidic pore networks. AB - Two-phase immiscible displacement in porous media is controlled by capillary and viscous forces when gravitational effects are negligible. The relative importance of these forces is quantified through the dimensionless capillary number Ca and the viscosity ratio M between fluid phases. When the displacing fluid is Newtonian, the effects of Ca and M on the displacement patterns can be evaluated independently. However, when the injecting fluids exhibit shear-thinning viscosity behaviour the values of M and Ca are interdependent. Under these conditions, the effects on phase entrapment and the general displacement dynamics cannot be dissociated. In the particular case of shear-thinning aqueous polymer solutions, the degree of interdependence between M and Ca is determined by the polymer concentration. In this work, two-phase immiscible displacement experiments were performed in micromodels, using shear-thinning aqueous polymer solutions as displacing fluids, to investigate the effect of polymer concentration on the relationship between Ca and M, the recovery efficiency, and the size distribution of the trapped non-wetting fluid. Our results show that the differences in terms of magnitude and distribution of the trapped phase are related to the polymer concentration which influences the values of Ca and M. PMID- 26998788 TI - Debate: creating adequate pulse with a continuous flow ventricular assist device: can it be done and should it be done? Probably not, it may cause more problems than benefits! AB - PURPOSE OF REVIEW: The feasibility and benefits of creating adequate pulsatility with continuous flow left ventricular assist devices (LVADs) have long been debated. This review discusses recent technical and clinical findings to answer whether such intervention should be implemented in the standard patient management. RECENT FINDINGS: Only a limited amount of pulsatility can be generated by periodic speed steps, both considerably smaller in flow increase and in pace rate than the natural circulation. Organ systems are not impeded in their normal function and even not in recovery by a continuous flow. Known problems such as gastrointestinal bleeding are not necessarily due to pulsatility per se, or not important for therapeutic progress, such as minor modifications of the arterial walls. SUMMARY: The speculative benefits of augmented pulsatility with continuous flow LVADs could be overrated and are still incompletely evaluated. Potential risks that might arise from this strategy should be carefully weighed before implementing extensive pulsatility as standard patient management. PMID- 26998790 TI - Potential Association Between Atrial Fibrillation and Dementia. PMID- 26998789 TI - Preventing Postpartum Smoking Relapse: A Randomized Clinical Trial. AB - IMPORTANCE: Most women who quit smoking during pregnancy will relapse postpartum. Previous efforts to prevent postpartum relapse have been unsuccessful at increasing rates of sustained abstinence. OBJECTIVE: To evaluate the relative efficacy of 2 different approaches to prevent postpartum smoking relapse. DESIGN, SETTING, AND PARTICIPANTS: Pregnant women who recently had quit smoking were recruited before the end of pregnancy. Intervention sessions were conducted through a combination of telephone calls and in-person visits beginning at delivery and continuing through 24 weeks postpartum. Participants completed assessments at the prenatal baseline and at 12, 24, and 52 weeks postpartum. Participants were recruited between March 2008 and December 2012. The dates of the analysis were April 2014 to February 2015. INTERVENTIONS: Women received postpartum-adapted, behavioral smoking relapse prevention intervention and were randomly assigned to an enhanced cognitive behavioral intervention that included additional specialized strategies and content focused on women's postpartum concerns about mood, stress, and weight (Strategies to Avoid Returning to Smoking [STARTS]) or a supportive, time and attention-controlled comparison (SUPPORT). Intervention began before delivery and continued through 24 weeks postpartum. MAIN OUTCOMES AND MEASURES: The primary outcome was biochemically confirmed sustained tobacco abstinence at 52 weeks postpartum. Secondary outcomes were self reported mood, levels of perceived stress, and degree of concern about smoking related weight gain. RESULTS: The study cohort comprised 300 participants (150 randomly assigned to each group). Their mean (SD) age was 24.99 (5.65) years. Overall, 38.0% (114 of 300), 33.7% (101 of 300), and 24.0% (72 of 300) of the sample maintained abstinence at 12, 24, and 52 weeks' postpartum, respectively. There were no differences between the intervention groups in abstinence or time to relapse. Self-reported depressive symptoms and perceived stress significantly improved over time, and improvements were similar for both intervention groups. Women with more depressive symptoms and higher levels of perceived stress were more likely to relapse (hazard ratio, 1.02; 95% CI, 1.00-1.04; P = .04 for depressive symptoms and hazard ratio, 1.04; 95% CI, 1.01-1.07; P = .003 for stress). CONCLUSIONS AND RELEVANCE: An intervention designed to address women's concerns about mood, stress, and weight did not differentially improve rates of sustained tobacco abstinence postpartum compared with a time and attention controlled comparison. Women in STARTS and SUPPORT reported postpartum improvements in mood and stress, and the experience of fewer depressive symptoms and less perceived stress was related to sustained abstinence. Given that most pregnant quitters will relapse within 1 year postpartum and that postpartum smoking has negative health consequences for women and children, effective interventions that target postpartum mood and stress are needed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00757068. PMID- 26998792 TI - Characteristics of depressive patients according to family history of affective illness: Findings from a French national cohort. AB - BACKGROUND: Literature is scarce about the characteristics of mood disorder patients with a family history (FH) of affective illness. The aim of the current study was to compare the prominent features of depressive patients with a FH of mania (FHM), those of depressive patients with a FH of depression (FHD), and those of depressive patients with no FH of affective illness (FHO). METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 45 (9.1%) were classified as FHM, 210 (42.6%) as FHD, and 238 (48.3%) as FHO. RESULTS: The main characteristics of FHM patients were a cyclothymic temperament, the presence of mixed features and diurnal variations of mood during depression, early sexual behaviour, a high number of mood episodes and hypomanic switches, high rates of suicide attempts and rapid cycling; diagnosis of bipolar disorder was more frequent in this group as well as comorbid obsessive compulsive disorder, posttraumatic stress disorder, bulimia, attention deficit/hyperactivity disorder and impulse control disorders. The FHD patients had more depressive temperament, generalized anxiety disorder, and anorexia nervosa. Compared to FHO, FHM and FHD showed an earlier age at onset, more comorbid anxiety disorders, as well as more psychotic features. LIMITATIONS: The following are the limitations of this study: retrospective design, recall bias, and preferential enrolment of bipolar patients with a depressive predominant polarity. CONCLUSIONS: In light of genetic studies conducted in affective disorder patients, our findings may support the hypothesis of genetic risks factors common to affective disorders and dimensions of temperament, that may extend to comorbid conditions specifically associated with bipolar or unipolar illness. PMID- 26998793 TI - Does psychosis increase the risk of suicide in patients with major depression? A systematic review. AB - OBJECTIVE: Over the years studies have shown conflicting results about the risk of suicide in psychotic depression (MD-psych). To understand this association, we undertook a comprehensive review of the literature to ascertain whether individuals with MD-psych have higher rates of completed suicides, suicide attempts or suicidal ideation compared to those with non-psychotic depression (MD nonpsych). METHODS: We searched Pubmed, PsycINFO and Ovid in English language, from 1946-October 2015. Studies were included if suicidal ideation, attempts or completed suicides were assessed. RESULTS: During the acute episode of depression, patients with MD-psych have higher rates of suicide, suicide attempts, and suicidal ideation than patients with MD-nonpsych, especially when the patient is hospitalized on an inpatient psychiatric unit. Studies done after the acute episode has resolved are less likely to show this difference, likely due to patients having received treatment. LIMITATIONS: Diagnostic interviews were not conducted in all studies. Many studies did not report whether psychotic symptoms in MD-psych patients were mood-congruent or mood-incongruent; hence it is unclear whether the type of delusion increases suicide risk. Studies did not describe whether MD-psych patients experienced command hallucinations encouraging them to engage in suicidal behavior. Only 24 studies met inclusion criteria; several of them had small sample size and a quality score of zero, hence impacting validity. CONCLUSIONS: This review indicates that the seemingly conflicting data in suicide risk between MD-psych and MD-nonpsych in previous studies appears to be related to whether one looks at differences during the acute episode or over the long-term. PMID- 26998791 TI - The role of vitamin D in the prevention of late-life depression. AB - BACKGROUND: In this article, we review current evidence regarding potential benefits of vitamin D for improving mood and reducing depression risk in older adults. We summarize gaps in knowledge and describe future efforts that may clarify the role of vitamin D in late-life depression prevention. METHODS: MEDLINE and PsychINFO databases were searched for all articles on vitamin D and mood that had been published up to and including May 2015. Observational studies and randomized trials with 50 or more participants were included. We excluded studies that involved only younger adults and/or exclusively involved persons with current depression. RESULTS: Twenty observational (cross-sectional and prospective) studies and 10 randomized trials (nine were randomized placebo controlled trials [RCTs]; one was a randomized blinded comparison trial) were reviewed. Inverse associations of vitamin D blood level or vitamin D intake with depression were found in 13 observational studies; three identified prospective relations. Results from all but one of the RCTs showed no statistically significant differences in depression outcomes between vitamin D and placebo groups. LIMITATIONS: Observational studies were mostly cross-sectional and frequently lacked adequate control of confounding. RCTs often featured low treatment doses, suboptimal post-intervention changes in biochemical levels of vitamin D, and/or short trial durations. CONCLUSION: Vitamin D level-mood associations were observed in most, but not all, observational studies; results indicated that vitamin D deficiency may be a risk factor for late-life depression. However, additional data from well-designed RCTs are required to determine the impact of vitamin D in late-life depression prevention. PMID- 26998794 TI - Exercise in bipolar patients: A systematic review. AB - BACKGROUND: Sedentary lifestyle is frequent in psychiatric disorders, however the directions of this association and benefits of physical activity are unclear. This is a systematic review about exercise in patients with bipolar disorder. METHODS: We performed a systematic literature search of studies published in English (1995 Jan to 2016 Jan) in PubMed, and Cochrane Library combining the medical terms 'physical activity' or 'sedentary' or 'physical exercise' with 'bipolar disorder' or 'mania' or 'bipolar depression'. RESULTS: Thirty-one studies were selected and included 15,587 patients with bipolar disorder. Sedentary lifestyle varied from 40% to 64.9%. Physical activity was associated with less depressive symptoms, better quality of life and increased functioning. Some evidence indicates a relationship between vigorous exercises and mania. Three prospective cohorts were reported; and no prospective randomized controlled trial was identified. Three studies focused on biomarkers in bipolar patients; and one reported the relationship between exercise and sleep in this group. Two assessed physical exercise in adolescents. LIMITATIONS: (1) Differences between studies preventing a unified analysis; (2) most studies were cross-sectional; (3) motivation for exercising is a selection bias in most studies; (4) no intervention study assessing only physical exercise; (5) lack of studies comparing exercise across mood states. CONCLUSION: Generally, exercise was associated with improved health measures including depressive symptoms, functioning and quality of life. Evidence was insufficient to establish a cause effect relationship between mood and physical exercise. Future research including randomized trials is needed to clarify the role of physical activity in bipolar patients. PMID- 26998795 TI - Practising on plastic people: Can I really care? AB - PURPOSES: This study evaluated the experiences of undergraduate student nurses with high-fidelity Human Patient Simulation Mannequins (HPSMs) and their perceptions of empathy. METHODS: An exploratory case-study method was used to investigate the literature on empathy and the use of high-fidelity mannequins in nurse education. Two focus groups were conducted with eight third-year undergraduate nursing students in order to elicit responses to their experiences with HPSMs in their learning, especially in relation to empathy. FINDINGS: Undergraduate nurses found it challenging when using HPSMs in the learning environment to relate to the mannequins as real. Students reported that in their experience, the use of mannequins was not conducive currently to the development of skills necessary for positive interpersonal development of the nurse-patient relationship. CONCLUSIONS: Focus group data and the empirical literature suggest that more research needs to be conducted into the use of mannequins in the development of nurse-patient interpersonal skills. Educators need to make evidence-based and pedagogically sound decisions about the use and limitations of HPSMs in undergraduate nursing. PMID- 26998796 TI - Nitrification and microalgae cultivation for two-stage biological nutrient valorization from source separated urine. AB - Urine contains the majority of nutrients in urban wastewaters and is an ideal nutrient recovery target. In this study, stabilization of real undiluted urine through nitrification and subsequent microalgae cultivation were explored as strategy for biological nutrient recovery. A nitrifying inoculum screening revealed a commercial aquaculture inoculum to have the highest halotolerance. This inoculum was compared with municipal activated sludge for the start-up of two nitrification membrane bioreactors. Complete nitrification of undiluted urine was achieved in both systems at a conductivity of 75mScm(-1) and loading rate above 450mgNL(-1)d(-1). The halotolerant inoculum shortened the start-up time with 54%. Nitrite oxidizers showed faster salt adaptation and Nitrobacter spp. became the dominant nitrite oxidizers. Nitrified urine as growth medium for Arthrospira platensis demonstrated superior growth compared to untreated urine and resulted in a high protein content of 62%. This two-stage strategy is therefore a promising approach for biological nutrient recovery. PMID- 26998797 TI - Can aquatic worms enhance methane production from waste activated sludge? AB - Although literature suggests that aquatic worms can help to enhance the methane production from excess activated sludge, clear evidence for this is missing. Therefore, anaerobic digestion tests were performed at 20 and at 30 degrees C with sludge from a high-loaded membrane bioreactor, the aquatic worm Lumbriculus variegatus, feces from these worms and with mixtures of these substrates. A significant synergistic effect of the worms or their feces on methane production from the high-loaded sludge or on its digestion rate was not observed. However, a positive effect on low-loaded activated sludge, which generally has a lower anaerobic biodegradability, cannot be excluded. The results furthermore showed that the high-loaded sludge provides an excellent feed for L. variegatus, which is promising for concepts where worm biomass is considered a resource for technical grade products such as coatings and glues. PMID- 26998798 TI - Effect of cobalt supplementation and fractionation on the biological response in the biomethanization of Olive Mill Solid Waste. AB - Due to the low trace metals concentration in the Olive Mill Solid Waste (OMSW), a proposed strategy to improve its biomethanization is the supplementation of key metals to enhance the microorganism activity. Among essential trace metals, cobalt has been reported to have a crucial role in anaerobic degradation. This study evaluates the effect of cobalt supplementation to OMSW, focusing on the connection between fractionation of cobalt in the system and the biological response. The highest biological responses was found in a range from 0.018 to 0.035mg/L of dissolved cobalt (0.24-0.65mg total cobalt/L), reaching improvements up to 23% and 30% in the methane production rate and the methane yield coefficient, respectively. It was found that the dissolved cobalt fraction is more accurately related with the biological response than the total cobalt. The total cobalt is distorted by the contribution of dissolved and non-dissolved inert fractions. PMID- 26998800 TI - Gradients of relative disparity underlie the perceived slant of stereoscopic surfaces. AB - Perceived stereoscopic slant around a vertical axis is strongly underestimated for isolated surfaces, suggesting that neither uniocular image compression nor linear gradients of absolute disparity are very effective cues. However, slant increases to a level close to geometric prediction if gradients of relative disparity are introduced, for example by placing flanking frontal-parallel surfaces at the horizontal boundaries of the slanted surface. Here we examine the mechanisms underlying this slant enhancement by manipulating properties of the slanted surface or the flanking surfaces. Perceived slant was measured using a probe bias method. In Experiment 1, an outlined surface and a randomly textured surface showed similar slant underestimation when presented in isolation, but the enhancement in slant produced by flankers was significantly greater for the textured surface. In Experiment 2, we degraded the relative disparity gradient by (a) reducing overall texture density, (b) reducing flanker width, or (c) adding disparity noise to the flankers. Density had no effect while adding noise to the flankers, or reducing their width significantly decreased perceived slant of the central surface. These results support the view that the enhancement of slant produced by adding flanking surfaces is attributable to the presence of a relative disparity gradient and that the flanker effect can spread to regions of the surface not directly above or below the gradient. PMID- 26998799 TI - Inhibiting excessive acidification using zero-valent iron in anaerobic digestion of food waste at high organic load rates. AB - Excessive acidification occurs frequently in food waste (FW) anaerobic digestion (AD) due to the high carbon-to-nitrogen ratio of FW. In this study, zero-valent iron (ZVI) was applied to prevent the excessive acidification. All of the control groups, without ZVI addition (pH~5.3), produced little methane (CH4) and had high volatile fatty acids/bicarbonate alkalinity (VFA/ALK). By contrast, at OLR of 42.32gVS/Lreactor, the pH of effluent from the reactors with 0.4g/gVSFWadded of ZVI increased to 7.8-8.2, VFA/ALK decreased to <0.1, and the final CH4 yield was ~380mL/gVSFWadded, suggesting inhibition of excessive acidification. After adding powdered or scrap metal ZVI to the acidogenic reactors, the fractional content of butyric acid changed from 30-40% to 0%, while, that of acetic acid increased. These results indicate that adding ZVI to FW digestion at high OLRs could eliminate excessive acidification by promoting butyric acid conversion and enhancing methanogen activity. PMID- 26998802 TI - Development of salience-driven and visually-guided eye movement responses. AB - Development of visuospatial attention can be quantified from infancy onward using visually-guided eye movement responses. We investigated the interaction between eye movement response times and salience in target areas of visual stimuli over age in a cohort of typically developing children. A preferential looking (PL) paradigm consisting of stimuli with six different visual modalities (cartoons, contrast, form, local motion, color, global motion) was combined with the automated measurement of reflexive eye movements. Effective salience was defined as visual salience of each target area relative to its background. Three classes of PL stimuli were used: with high- (cartoon, contrast), intermediate- (local motion, form), and low-effective salience (global motion, color). Eye movement response times to the target areas of the six PL stimuli were nonverbally assessed in 220 children aged 1-12 years. The development of response times with age was influenced by effective salience: Response times to targets with high salience reached stable values earlier in development (around 4 years of age) than to targets with low salience (around 9 years of age). Intra-individual response time variability was highest for low-salient stimuli, and stabilized later (around 4 years) than for highly salient stimuli (2 years). The improvement of eye movement response times to visual modalities in PL stimuli occurred earlier in development for highly salient than for low-salient targets. The present age-dependent and salience-related results provide a quantitative and theoretical framework to assess the development of visuospatial attention, and of related visual processing capacities, in children from 1 year of age. PMID- 26998801 TI - Typical magnitude and spatial extent of crowding in autism. AB - Enhanced spatial processing of local visual details has been reported in individuals with autism spectrum conditions (ASC), and crowding is postulated to be a mechanism that may produce this ability. However, evidence for atypical crowding in ASC is mixed, with some studies reporting a complete lack of crowding in autism and others reporting a typical magnitude of crowding between individuals with and without ASC. Here, we aim to disambiguate these conflicting results by testing both the magnitude and the spatial extent of crowding in individuals with ASC (N = 25) and age- and IQ-matched controls (N = 23) during an orientation discrimination task. We find a strong crowding effect in individuals with and without ASC, which falls off as the distance between target and flanker is increased. Both the magnitude and the spatial range of this effect were comparable between individuals with and without ASC. We also find typical (uncrowded) orientation discrimination thresholds in individuals with ASC. These findings suggest that the spatial extent of crowding is unremarkable in ASC, and is therefore unlikely to account for the visual symptoms reported in individuals with the diagnosis. PMID- 26998803 TI - Acceptance and Commitment Therapy versus Cognitive Behavior Therapy for Children With Anxiety: Outcomes of a Randomized Controlled Trial. AB - Acceptance and Commitment Therapy (ACT) has a growing empirical base in the treatment of anxiety among adults and children with other concerns. This study reports on the main outcomes of a randomized controlled trial of ACT and traditional cognitive behavioral therapy (CBT) in children with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) anxiety disorder. Participants were 193 children from urban Sydney, Australia, who were block-randomized to a 10 week group-based program of ACT or CBT or a 10-week waitlist control (WLC). Completers included 157 children (ACT = 54, CBT = 57, WLC = 46; M = 11 years, SD = 2.76; 78% Caucasian, 58% female). Pretreatment, posttreatment, and 3 months posttreatment assessments included clinician/self/parent-reported measures of anxiety, quality of life (QOL; anxiety interference, psychosocial and physical health-related QOL), and acceptance/defusion outcomes. Completer and intention-to treat analyses revealed that ACT and CBT were both superior to WLC across outcomes, reflecting statistically and clinically significant differences, with gains maintained at 3 months posttreatment. Both completer and intention-to-treat analyses found ACT and CBT to produce similar outcomes. There was some support for ACT having greater effect sizes for QOL outcomes but not for avoidance/fusion. Although this study does not suggest that ACT is equivalent to CBT or should be adopted in its place, it does provide evidence that ACT might be another empirically supported treatment option for anxious youth. Further research is needed to replicate these findings. PMID- 26998804 TI - Middle East Respiratory Syndrome Coronavirus: What Does a Radiologist Need to Know? AB - OBJECTIVE: The overarching goal of this article is to provide radiologists with the most up-to-date information regarding the underlying epidemiology, pathophysiology, clinical features, and imaging findings related to Middle East respiratory syndrome coronavirus (MERS-CoV), a potentially deadly new infection. CONCLUSION: An increased awareness of MERS-CoV and an understanding of the radiologic features of MERS-CoV can improve the early assessment and monitoring of this new infection. Radiologists can provide information based on chest radiographic and CT scores that can be helpful for patient management and predicting prognosis. PMID- 26998805 TI - Maternal and neonatal pneumococcal vaccination - where are we now? AB - Pneumococcus is a significant pathogen in neonates and in early infancy, particularly as a cause of invasive disease in sub-Saharan Africa where nasopharyngeal carriage rates are also exceptionally high. The pneumococcal conjugate vaccines have now been rolled out in many high income settings and an increasing number of low and middle income countries. They have been highly effective at preventing vaccine serotype disease in infants. However, a window of susceptibility remains prior to the first vaccination at around six weeks of age. This paper summarizes the data available on both maternal and neonatal vaccination to prevent disease in newborns and early infancy and considers the key challenges and next steps for research in the field. PMID- 26998806 TI - Dynamic development of the pancreas from birth to adulthood. AB - After birth the endocrine pancreas continues its development, a complex process that involves both the maturation of islet cells and a marked expansion of their numbers. New beta cells are formed both by duplication of pre-existing cells and by new differentiation (neogenesis) across the first postnatal weeks, with the result of beta cells of different stages of maturation even after weaning. Improving our understanding of this period of beta cell expansion could provide valuable therapeutic insights. PMID- 26998807 TI - Which behaviours? Identifying the most common and burdensome behaviour changes in amyotrophic lateral sclerosis. AB - Behaviour change is increasingly recognised as a common feature of amyotrophic lateral sclerosis (ALS), and may be similar to that seen in frontotemporal dementia (FTD). The behaviours most disturbed in ALS, and those that relate most significantly to caregiver burden, however, have not been well established. Forty ALS participants and their caregivers, and 27 age- and gender-matched healthy controls and their relatives, participated in this study. ALS participants were assessed on a disease rating scale, and caregivers and control informants completed the revised version of the Cambridge Behaviour Inventory and a measure of burden. ALS caregivers reported significantly more disturbance than healthy control informants on the functional domains of everyday skills, self-care, and sleep, and in the behavioural domains of mood and motivation. There were no differences between groups in frequency of memory and orientation difficulties, or behaviours characteristic of FTD, such as changes to eating habits or stereotypic and motor behaviour, indicating that the behavioural profile in ALS may differ from FTD. In the ALS group, the domains with the strongest relationship to caregiver burden were everyday skills, motivation and memory, likely because poor motivation, memory dysfunction and difficulties completing activities of daily living require more carer support via direct supervision, prompting or hands on care. Services to support ALS patients and caregivers need to provide targeted interventions for those functional and behavioural changes which are most burdensome in the disease. PMID- 26998808 TI - Are plant sterols and plant stanols a viable future treatment for dyslipidemia? PMID- 26998809 TI - Bone thickness of the anterior palate for orthodontic miniscrews. AB - OBJECTIVE: To determine the bone thickness in the anterior palate and to test whether there is any dependency between bone thickness and patient's age or gender and whether there is any difference between left and right sides. MATERIALS AND METHODS: Cone beam computed tomographic (CBCT) evaluations (n = 431; 229 females, 202 males) of healthy orthodontic patients aged 9-30 years were selected from the database of the imaging center network Mesantis. In each CBCT image, palatal bone thickness was determined as the median and 2, 4, 6, and 8 mm paramedian bilaterally. Bone height was measured perpendicularly to the bony surface at 10, 12, 14, 16, 18, and 20 mm from the cementoenamel junction of the maxillary central incisor in the sagittal plane. RESULTS: The greatest bone thickness was found in the lateral anterior palate. Palatal bone thickness of male patients was on average 1.2 mm greater than that of females. Bone height of 9-13-year-olds was less than that of older patients. No difference could be determined between the left and right side. CONCLUSIONS: The lateral anterior palate offers the greatest bone thickness. Because there is considerable variation of bone thickness between individuals, a CBCT evaluation is recommended if maximum screw length is to be used. PMID- 26998810 TI - Bond strength and interfacial morphology of orthodontic brackets bonded to eroded enamel treated with calcium silicate-sodium phosphate salts or resin infiltration. AB - OBJECTIVE: To investigate the shear bond strength (SBS) of orthodontic brackets bonded to eroded enamel treated with preventive approaches and to examine the enamel/bracket interfaces. MATERIALS AND METHODS: Ninety-one brackets were bonded to seven groups of enamel samples: sound; eroded; eroded+treated with calcium silicate-sodium phosphate salts (CSP); eroded+infiltrated by ICON(r); eroded+infiltrated by ICON(r) and brackets bonded with 1-month delay; eroded+infiltrated by an experimental resin; and eroded+infiltrated by an experimental resin and brackets bonded with 1-month delay. For each group, 12 samples were tested in SBS and bond failure was assessed with the adhesive remnant index (ARI); one sample was examined using scanning electron microscopy (SEM). RESULTS: Samples treated with CSP or infiltration showed no significant differences in SBS values with sound samples. Infiltrated samples followed by a delayed bonding showed lower SBS values. All of the values remained acceptable. The ARI scores were significantly higher for sound enamel, eroded, and treated with CSP groups than for all infiltrated samples. SEM examinations corroborated the findings. CONCLUSIONS: Using CSP or resin infiltration before orthodontic bonding does not jeopardize the bonding quality. The orthodontic bonding should be performed shortly after the resin infiltration. PMID- 26998811 TI - Study of the partition coefficients Kp/f of seven model migrants from LDPE polymer in contact with food simulants. AB - This study evaluated the influence of parameters such as temperature and type of low-density polyethylene (LDPE) film on the log Kp/f values of seven model migrants in food simulants. Two different types of LDPE films contaminated by extrusion and immersion were placed in contact with three food simulants including 20% ethanol, 50% ethanol and olive oil under several time-temperature conditions. Results suggest that most log Kp/f values are little affected by these parameters in this study. In addition, the relation between log Kp/f and log Po/w was established for each food simulant and regression lines, as well as correlation coefficients, were calculated. Correlations were compared with data from real foodstuffs. Data presented in this study could be valuable in assigning certain foods to particular food simulants as well as predicting the mass transfer of potential migrants into different types of food or food simulants, avoiding tedious and expensive laboratory analysis. The results could be especially useful for regulatory agencies as well as for the food industry. PMID- 26998812 TI - Qualitative extension of the EC' Zone Diagram to a molecular catalyst for a multi electron, multi-substrate electrochemical reaction. AB - The EC' Zone Diagram, introduced by Saveant and Su over 30 years ago, has been used to classify voltammetric responses for electrocatalytic systems. With a single H2-evolving catalyst, Co(dmgBF2)2(CH3CH)2 (dmgBF2 = difluoroboryl dimethylglyoxime), and a series of para-substituted anilinium acids, experimental conditions were carefully tuned to access to each region of the classic zone diagram. Close scrutiny revealed the extent to which the kinetic (lambda) and excess (gamma) factors could be experimentally controlled and used to access a variety of waveforms for this ECEC' catalytic system. It was found that most of the tunable experimental parameters (such as catalyst concentration, scan rate, and substrate concentration) predicted in the EC' Zone Diagram could be extended to a multi-electron system and produced similarly-shaped waveforms with some deviations. Tuning of a single catalyst across every region of the classic zone diagram has previously been prevented due to the seven orders of magnitude that need to be traversed across the kinetic parameter; however, the cobalt catalyst in this study provided unique control of this parameter. By varying the acids used as the proton source, the rate constants for protonation were tuned via a pKa-dependent linear free energy relationship. PMID- 26998813 TI - Enantioselective Aminomethylamination of Conjugated Dienes with Aminals Enabled by Chiral Palladium Complex-Catalyzed C-N Bond Activation. AB - A novel highly enantioselective aminomethylamination of conjugated dienes with aminals catalyzed by a chiral palladium complex ligated with BINOL-derived chiral diphosphinite has been successfully developed. This reaction proceeds via a Pd catalyzed cascade C-N bond activation, aminomethylation, and asymmetric allylic amination reaction under mild reaction conditions, providing a unique and efficient strategy for the synthesis of enantiomerically pure allylic 1,3 diamines. PMID- 26998815 TI - Dissecting the Factors Affecting the Fluorescence Stability of Quantum Dots in Live Cells. AB - Labeling and imaging of live cells with quantum dots (QDs) has attracted great attention in the biomedical field over the past two decades. Maintenance of the fluorescence of QDs in a biological environment is crucial for performing long term cell tracking to investigate the proliferation and functional evolution of cells. The cell-penetrating peptide transactivator of transcription (TAT) is a well-studied peptide to efficiently enhance the transmembrane delivery. Here, we used TAT peptide-conjugated QDs (TAT-QDs) as a model system to examine the fluorescence stability of QDs in live cells. By confocal microscopy, we found that TAT-QDs were internalized into cells by endocytosis, and transported into the cytoplasm via the mitochondria, Golgi apparatus, and lysosomes. More importantly, the fluorescence of TAT-QDs in live cells was decreased mainly by cell proliferation, and the low pH value in the lysosomes could also lower the fluorescence intensity of intracellular QDs. Quantitative analysis of the amount of QDs in the extracellular region and whole cells indicated that the exocytosis was not the primary cause of fluorescence decay of intracellular QDs. This work facilitates a better understanding of the fluorescence stability of QDs for cell imaging and long-term tracking in live cells. Also, it provides insights into the utility of TAT for transmembrane transportation, and the preparation and modification of QDs for cell imaging and tracking. PMID- 26998814 TI - Raman Shifts in Electron-Irradiated Monolayer MoS2. AB - We report how the presence of electron-beam-induced sulfur vacancies affects first-order Raman modes and correlate the effects with the evolution of the in situ transmission-electron microscopy two-terminal conductivity of monolayer MoS2 under electron irradiation. We observe a red-shift in the E' Raman peak and a less pronounced blue-shift in the A'1 peak with increasing electron dose. Using energy-dispersive X-ray spectroscopy and selected-area electron diffraction, we show that irradiation causes partial removal of sulfur and correlate the dependence of the Raman peak shifts with S vacancy density (a few %). This allows us to quantitatively correlate the frequency shifts with vacancy concentration, as rationalized by first-principles density functional theory calculations. In situ device current measurements show an exponential decrease in channel current upon irradiation. Our analysis demonstrates that the observed frequency shifts are intrinsic properties of the defective systems and that Raman spectroscopy can be used as a quantitative diagnostic tool to characterize MoS2-based transport channels. PMID- 26998817 TI - Atypical Exciton-Phonon Interactions in WS2 and WSe2 Monolayers Revealed by Resonance Raman Spectroscopy. AB - Resonant Raman spectroscopy is a powerful tool for providing information about excitons and exciton-phonon coupling in two-dimensional materials. We present here resonant Raman experiments of single-layered WS2 and WSe2 using more than 25 laser lines. The Raman excitation profiles of both materials show unexpected differences. All Raman features of WS2 monolayers are enhanced by the first optical excitations (with an asymmetric response for the spin-orbit related XA and XB excitons), whereas Raman bands of WSe2 are not enhanced at XA/B energies. Such an intriguing phenomenon is addressed by DFT calculations and by solving the Bethe-Salpeter equation. These two materials are very similar. They prefer the same crystal arrangement, and their electronic structure is akin, with comparable spin-orbit coupling. However, we reveal that WS2 and WSe2 exhibit quite different exciton-phonon interactions. In this sense, we demonstrate that the interaction between XC and XA excitons with phonons explains the different Raman responses of WS2 and WSe2, and the absence of Raman enhancement for the WSe2 modes at XA/B energies. These results reveal unusual exciton-phonon interactions and open new avenues for understanding the two-dimensional materials physics, where weak interactions play a key role coupling different degrees of freedom (spin, optic, and electronic). PMID- 26998816 TI - Mechanism of Germacradien-4-ol Synthase-Controlled Water Capture. AB - The sesquiterpene synthase germacradiene-4-ol synthase (GdolS) from Streptomyces citricolor is one of only a few known high-fidelity terpene synthases that convert farnesyl diphosphate (FDP) into a single hydroxylated product. Crystals of unliganded GdolS-E248A diffracted to 1.50 A and revealed a typical class 1 sesquiterpene synthase fold with the active site in an open conformation. The metal binding motifs were identified as D(80)DQFD and N(218)DVRSFAQE. Some bound water molecules were evident in the X-ray crystal structure, but none were obviously positioned to quench a putative final carbocation intermediate. Incubations in H2(18)O generated labeled product, confirming that the alcohol functionality arises from nucleophilic capture of the final carbocation by water originating from solution. Site-directed mutagenesis of amino acid residues from both within the metal binding motifs and without identified by sequence alignment with aristolochene synthase from Aspergillus terreus generated mostly functional germacradien-4-ol synthases. Only GdolS-N218Q generated radically different products (~50% germacrene A), but no direct evidence of the mechanism of incorporation of water into the active site was obtained. Fluorinated FDP analogues 2F-FDP and 15,15,15-F3-FDP were potent noncompetitive inhibitors of GdolS. 12,13-DiF-FDP generated 12,13-(E)-beta-farnesene upon being incubated with GdolS, suggesting stepwise formation of the germacryl cation during the catalytic cycle. Incubation of GdolS with [1-(2)H2]FDP and (R)-[1-(2)H]FDP demonstrated that following germacryl cation formation a [1,3]-hydride shift generates the final carbocation prior to nucleophilic capture. The stereochemistry of this shift is not defined, and the deuteron in the final product was scrambled. Because no clear candidate residue for binding of a nucleophilic water molecule in the active site and no significant perturbation of product distribution from the replacement of active site residues were observed, the final carbocation may be captured by a water molecule from bulk solvent. PMID- 26998818 TI - Population attributable fractions of risk factors for hepatocellular carcinoma in the United States. AB - BACKGROUND: Hepatocellular carcinoma (HCC) incidence has been increasing in the United States for several decades; and, as the incidence of hepatitis C virus (HCV) infection declines and the prevalence of metabolic disorders rises, the proportion of HCC attributable to various risk factors may be changing. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare linkage were used to calculate population attributable fractions (PAFs) for each risk factor over time. Patients with HCC (n = 10,708) who were diagnosed during the years 2000 through 2011 were compared with a 5% random sample of cancer-free controls (n = 332,107) residing in the Surveillance, Epidemiology, and End Results areas. Adjusted odds ratios (ORs) and PAFs were calculated for HCV, hepatitis B virus (HBV), metabolic disorders, alcohol-related disorders, smoking, and genetic disorders. RESULTS: Overall, the PAF was greatest for metabolic disorders (32%), followed by HCV (20.5%), alcohol (13.4%), smoking (9%), HBV (4.3%), and genetic disorders (1.5%). The PAF for all factors combined was 59.5%. PAFs differed by race/ethnicity and sex. Metabolic disorders had the largest PAF among Hispanics (PAF, 39.3%; 95% confidence interval [CI], 31.9%-46.7%) and whites (PAF, 34.8%; 95% CI, 33.1%-36.5%), whereas HCV had the largest PAF among blacks (PAF, 36.1%; 95% CI, 31.8%-40.4%) and Asians (PAF, 29.7%; 95% CI, 25.9%-33.4%). Between 2000 and 2011, the PAF of metabolic disorders increased from 25.8% (95% CI, 22.8% 28.9%) to 36% (95% CI, 33.6%-38.5%). In contrast, the PAFs of alcohol-related disorders and HCV remained stable. CONCLUSIONS: Among US Medicare recipients, metabolic disorders contribute more to the burden of HCC than any other risk factor, and the fraction of HCC caused by metabolic disorders has increased in the last decade. Cancer 2016;122:1757-65. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.. PMID- 26998819 TI - Outcome at 30 days for low-risk chest pain patients assessed using an accelerated diagnostic pathway in the emergency department. AB - OBJECTIVES: Primary: to determine incidence of 30 day major adverse cardiac events (MACE) in patients discharged from the ED following assessment using an accelerated diagnostic pathway (ADP). Secondary: to determine incidence of 30 day MACE for all ADP patients. METHODS: Monash Health ED patients thought at low risk for acute myocardial infarction (AMI) or hospital admission are assessed using an ADP, based on arrival and 90 min point-of-care (POC) cardiac troponin I and myoglobin concentration. Other patients are assessed using a traditional pathway of arrival and 6 h central lab cardiac troponin I. Choice of pathway is based on the clinical judgement of the attending ED doctor. To investigate the safety of the ADP component, an observational study of all ADP patients presenting from 6 June 2013 to 30 September 2013 was conducted. After 30 days, occurrence of MACE was determined by examination of hospital records or telephone contact with patients who had not returned. RESULTS: Of 1547 eligible patients, 1384 (89.5%) were followed up. Of the 1143 discharged patients with follow-up information, 30 day MACE occurred in one (0.09%, 95% CI 0.002-0.5). Of all 1547 patients, 60 patients had a MACE detected: 56 AMI during the initial attendance, four AMI post discharge (one from ED, three after hospital admission). In total, of the 1328 patients who did not have AMI during the target admission and were followed up, 30 day post-discharge MACE occurred in four patients (0.3%, 95% CI 0.08-0.8). CONCLUSION: The ADP supports safe, early discharge of low-risk chest pain patients from the ED. PMID- 26998820 TI - Vitamin D, HLA-DRB1 and Epstein-Barr virus antibody levels in a prospective cohort of multiple sclerosis patients. AB - BACKGROUND AND PURPOSE: Our objective was to study the association between serum levels of anti Epstein-Barr virus nuclear antigen 1 (EBNA-1) antibody and 25 hydroxyvitamin D (25(OH)D) in a prospective cohort of patients with relapsing remitting multiple sclerosis. METHOD: The study comprised 90 patients with relapsing-remitting multiple sclerosis, all participants in a randomized clinical trial of omega-3 fatty acids (the OFAMS study). Repeated, paired measurements of serum 25(OH)D and serum EBNA-1 immunoglobulin G (IgG) levels were obtained at baseline and every 6 months for 24 months. The association between serum EBNA-1 IgG and serum 25(OH)D levels was analysed using generalized linear models for hierarchical data. RESULTS: There was a significant variation in EBNA-1 IgG antibody level between sampling months (Fdf 11 = 1.8, P = 0.043, one-way anova). There was a negative association between EBNA-1 IgG and 25(OH)D [B = -0.230, 95% confidence interval (CI) (-0.440, -0.023), P = 0.030] and a positive association between EBNA-1 IgG and HLA-DRB1*15 positive status [B = 94.7, 95% CI (2.423, 186.9), P = 0.044]. The association between 25(OH)D and EBNA-1 IgG remained significant after adjusting for the patient's age, gender, HLA-DRB1*15, retinol levels and interferon beta-1a treatment. CONCLUSION: Our study demonstrates monthly differences in EBNA-1 IgG levels and an association between EBNA-1 IgG, 25(OH)D levels and HLA-DRB1*15. These results indicate that EBNA-1 IgG serum levels are affected by genetic and environmental factors that also modulate multiple sclerosis risk. PMID- 26998821 TI - Hypomorphic mutation in the hairless gene accelerates pruritic atopic skin caused by feeding a special diet to mice. PMID- 26998822 TI - [Application of paramunity inducers in small animal practice]. AB - Paramunity inducers have been used to treat small animals for decades. Paramunity inducers are based on attenuated and inactivated poxviruses (avipox virus and parapox virus). Their applications include both therapeutic and prophylactic use in various diseases. Despite their wide and variable use, only a very small number of placebo-controlled studies has been published. Positive effects in preventing kitten mortality and in treating feline stomatitis have been reported, however, no statistically significant effect of their therapeutic use in canine parvovirus infection, feline leukemia infection virus infection or canine papillomavirus infection could be demonstrated. For these infectious diseases, paramunity inducers do not appear to be effective. PMID- 26998824 TI - Alternating temperature combined with darkness resets base temperature for germination (Tb ) in photoblastic seeds of Lippia and Aloysia (Verbenaceae). AB - Thermal time models for seed germination assume a continuum of rate responses in the sub-optimal temperature range. Generally, the models describe germination performance in non-dormant seeds at constant temperatures, yet alternating temperature (AT) is a feature of many natural environments. We studied the possible interacting effects of AT on germination progress in photoblastic seeds of three aromatic-medicinal Verbenaceae species in the genera Lippia and Aloysia. For Lippia turbinata f. turbinata and L. turbinata f. magnifolia seed, germination only occurred in light conditions, while for L. integrifolia and Aloysia citriodora it was significantly higher in the light than in darkness. Although relative light germination (RLG) was not different between constant and AT in the sub-optimal range, AT raised the base temperature for germination progress (Tb ) from ca. 3-6 degrees C in constant temperature to 7-12 degrees C in AT. Among the species, thermal time for 50% seed germination [thetaT(50) ] was 55-100 degrees Cd at constant temperature. Although AT resulted in slight modifications to thetaT(50) , the germination rate at comparable average temperatures in the sub-optimal range was slower than under constant temperatures. For all species, the proportion of germinated seeds was similar for constant and AT. Our results suggest that an interaction between cool temperature and darkness during AT treatment limits the temperature range permissive for germination in these positively photoblastic seed, reflecting both close adaptation to the natural ecology and niche requirements of the species. PMID- 26998823 TI - Complex regulation of the regulator of synaptic plasticity histone deacetylase 2 in the rodent dorsal horn after peripheral injury. AB - Histone deacetylases (HDACs), HDAC2 in particular, have been shown to regulate various forms of learning and memory. Since cognitive processes share mechanisms with spinal nociceptive signalling, we decided to investigate the HDAC2 expression in the dorsal horn after peripheral injury. Using immunohistochemistry, we found that spinal HDAC2 was mainly seen in neurons and astrocytes, with neuronal expression in naive tissue 2.6 times greater than that in astrocytes. Cysteine (S)-nitrosylation of HDAC2 releases HDAC2 gene silencing and is controlled by nitric oxide (NO). A duration of 48 h after intraplantar injection of complete Freund's adjuvant, there was an ipsilateral increase in the most important NO-producing enzyme in pain states, nitric oxide synthase (nNOS), accompanied by an increase in HDAC2 S-nitrosylation. Moreover, a subset of nNOS positive neurons expressed cFos, a known target of HDAC2, suggesting that derepression of cFos expression following HDAC2 S-nitrosylation might occur after noxious stimulation. We saw no change in global HDAC2 expression in both short- and long-term pain states. However, HDAC2 was increased in astrocytes 7 days after neuropathic injury suggesting that HDAC2 might inhibit astrocytic gene expression in neuropathic pain states. All together, our results indicate that the epigenetic regulation of transcriptional programmes in the dorsal horn after injury is cell specific. Moreover, the prominent role of NO in persistent pain states suggests that HDAC2 S-nitrosylation could play a crucial role in the regulation of gene expression leading to hypersensitivity. Our manuscript describes for the first time the regulation of the memory regulator histone deacetylase 2 (HDAC2) in the superficial dorsal horn of adult rats following peripheral injury. Our cell-specific approach has revealed a complex pattern of expression of spinal HDAC2 that depends on the injury and the cell type, suggesting a sophisticated regulation of gene expression by HDAC2. PMID- 26998825 TI - Serous Cystadenocarcinoma of the Pancreas: Clinical Features and Management of a Rare Tumor. AB - BACKGROUND/AIMS: The vast majority of serous cystic neoplasms of the pancreas are benign, and small, asymptomatic lesions, which are generally managed with observation. However, some of these tumors may attain a large size and occasionally metastasize. METHODS: In this study, we present a 78-year-old man with serous cystadenocarcinoma of the pancreas with liver metastases treated by distal pancreatectomy and liver ablation, who went on to develop new liver metastases 5 years after the initial operation. We perform a literature review to determine the number of these malignant neoplasms previously reported and to identify features associated with malignant lesions. RESULTS: Literature reveals that metastatic serous cystadenocarcinomas of the pancreas are rare tumors, occurring in less than 3% of cases of serous cystic neoplasms. All malignant cases reported have been in tumors >4 cm in size. CONCLUSIONS: Serous cystic neoplasms of the pancreas >4 cm have malignant potential and therefore should be considered for surgical management. PMID- 26998826 TI - Synthesis of (E)-4-Bromo-3-methoxybut-3-en-2-one, the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A-C. AB - The terminal bromomethoxydiene (BMD) moiety of the polyhydroxylated chain present in phormidolides and oscillariolides has been synthesized for first time. Several strategies for the stereoselective synthesis of the 4-bromo-3-methoxybut-3-en-2 ones are described. Furthermore, a preliminary study to successfully introduce the BMD within the polyol chain and the fatty acid allowed us to corroborate the end structure of the polyol. PMID- 26998827 TI - International Society on Thrombosis and Haemostasis core curriculum project: core competencies in clinical thrombosis and hemostasis: reply. PMID- 26998828 TI - Management of Large Prostate Gland in Men with Impaired Renal Function: Comparison of Safety, Efficacy and Outcomes of Monopolar, Bipolar Transurethral Resection and Open Prostatectomy. AB - OBJECTIVE: The purpose of the study was to compare the safety, efficacy and outcome of monopolar transurethral resection of prostate (M-TURP), bipolar transurethral resection of prostate (BP-TURP) and open prostatectomy (OP) exclusively involving large prostate glands in men with renal impairment. METHODS: Data of patients with gland size >90 g and serum creatinine >1.5 mg/dl, who were managed surgically at our institution from April 2009 to March 2014 were analyzed retrospectively. International Prostate Symptom Score (IPSS), quality of life (QoL) scores, PVR, serum creatinine and Q-max were recorded preoperatively and postoperatively at each follow-up visit. Follow-up was performed at 1, 3, 6 and 12 months. RESULTS: M-TURP, BP-TURP and OP were the 3 types of surgeries performed. Preoperative characters were similar in all the groups. Hemoglobin drop, transfusion rates, irrigation time, catheter time and hospital days were significantly more in the OP group. Changes in sodium levels and incidence of transurethral syndrome were found to be more in the monopolar group. The follow up data indicate a significant improvement in the IPSS, QoL, PVR and Q-max in all the groups. CONCLUSION: This category of patients can be managed safely and efficiently by all the 3 procedures, although BP-TURP has an advantage in terms of shorter catheterization, hospitalization and fewer complications like transurethral resection syndrome. PMID- 26998829 TI - Palladium-Catalyzed Regio- and Stereoselective Carbothiolation of Terminal Alkynes with Azolyl Sulfides. AB - Palladium-catalyzed carbothiolation of terminal alkynes with azolyl sulfides affords various 2-(azolyl)alkenyl sulfides with perfect regio- and stereoselectivities. The present addition reaction proceeded through a direct cleavage of carbon-sulfur bonds in azolyl sulfides. The resulting adducts that are useful intermediates in organic synthesis are further transformed to multisubstituted olefins containing azolyl moieties. PMID- 26998831 TI - SOXC and MiR17-92 gene expression profiling defines two subgroups with different clinical outcome in mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is a heterogeneous B-cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR-17-92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL. In this study we screened the transcriptional profiles of 70 MCL patients for SOXC cluster and miR17, miR18a, miR19b and miR92a, from the miR-17-92 cluster. Gene expression analysis showed higher SOX11 and SOX12 levels compared to SOX4 (P <= 0.0026). Moreover we found a negative correlation between the expression of SOX11 and SOX4 (P < 0.0001). miR17-92 cluster analysis showed that miR19b and miR92a exhibited higher levels than miR17 and miR18a (P < 0.0001). Unsupervised hierarchical clustering revealed two subgroups with significant differences in relation to aggressive MCL features, such as blastoid morphological variant (P = 0.0412), nodal presentation (P = 0.0492), CD5(+) (P = 0.0004) and shorter overall survival (P < 0.0001). Together, our findings show for the first time an association between the differential expression profiles of SOXC and miR17-92 clusters in MCL and also relate them to different clinical subtypes of the disease adding new biological information that may contribute to a better understanding of this pathology. (c) 2016 Wiley Periodicals, Inc. PMID- 26998830 TI - Rights and Responsibilities of Tuberculosis Patients, and the Global Fund: A Qualitative Study. AB - BACKGROUND: Implementation of the Charter to protect patients' rights is an important criterion to achieve patient-centered approach and receive financial support from the Global Fund. Our study aims to explore the knowledge of tuberculosis (TB) patients about their rights and responsibilities at the Chest Disease Unit of the Bahawal Victoria Hospital, Bahawalpur, Pakistan. METHODS: This was a qualitative study. The data from purposefully selected TB patients was collected by in-depth interviews. Eligibility criteria included confirmed diagnosis of TB and enrollment in the TB program. A pilot tested interview protocol was based upon the objectives of the study, and was used uniformly in each interview to maintain the consistency. The sample size was limited by applying the saturation criteria. All interviews were audiotaped and transcribed verbatim. Inductive thematic content analysis was applied to analyze the data and draw conclusions. RESULTS: Out of the total 16 patients, four were female, and seven were illiterate. Eight patients were known cases of multi-drug resistant TB. Analysis of the data yielded seven themes; tuberculosis care services, moral support and stigmatization, dignity and privacy, complaints, fear of losing job, information sharing and compliance to the treatment plan, and contribution to eradicate TB. First five represented the rights section while latter two were related to the responsibilities section of the Charter. CONCLUSION: Discriminatory access to TB care services and the right to privacy were two major concerns identified in this study. However, the respondents recognized their responsibilities as a TB patient. To ensure uninterrupted investment from the Global Fund, there is a need to implement fair TB care policies which support human rights-based approach. PMID- 26998832 TI - Revealing Invisible Water: Moisture Recycling as an Ecosystem Service. AB - An ecosystem service is a benefit derived by humanity that can be traced back to an ecological process. Although ecosystem services related to surface water have been thoroughly described, the relationship between atmospheric water and ecosystem services has been mostly neglected, and perhaps misunderstood. Recent advances in land-atmosphere modeling have revealed the importance of terrestrial ecosystems for moisture recycling. In this paper, we analyze the extent to which vegetation sustains the supply of atmospheric moisture and precipitation for downwind beneficiaries, globally. We simulate land-surface evaporation with a global hydrology model and track changes to moisture recycling using an atmospheric moisture budget model, and we define vegetation-regulated moisture recycling as the difference in moisture recycling between current vegetation and a hypothetical desert world. Our results show that nearly a fifth of annual average precipitation falling on land is from vegetation-regulated moisture recycling, but the global variability is large, with many places receiving nearly half their precipitation from this ecosystem service. The largest potential impacts for changes to this ecosystem service are land-use changes across temperate regions in North America and Russia. Likewise, in semi-arid regions reliant on rainfed agricultural production, land-use change that even modestly reduces evaporation and subsequent precipitation, could significantly affect human well-being. We also present a regional case study in the Mato Grosso region of Brazil, where we identify the specific moisture recycling ecosystem services associated with the vegetation in Mato Grosso. We find that Mato Grosso vegetation regulates some internal precipitation, with a diffuse region of benefit downwind, primarily to the south and east, including the La Plata River basin and the megacities of Sao Paulo and Rio de Janeiro. We synthesize our global and regional results into a generalized framework for describing moisture recycling as an ecosystem service. We conclude that future work ought to disentangle whether and how this vegetation-regulated moisture recycling interacts with other ecosystem services, so that trade-offs can be assessed in a comprehensive and sustainable manner. PMID- 26998833 TI - Regionally Discrete Aqueous Humor Outflow Quantification Using Fluorescein Canalograms. AB - PURPOSE: To visualize and quantify conventional outflow directly in its anatomic location. METHODS: We obtained fluorescein canalograms in six porcine whole eyes and six porcine anterior segment cultures. Eyes were perfused with a constant pressure of 15 mmHg using media containing 0.017 mg/ml fluorescein. Flow patterns were visualized using a stereo dissecting microscope equipped for fluorescent imaging. Images were captured every 30 seconds for 20 minutes for time lapse analysis. Anterior chamber cultures were imaged again on day three of culture. Canalograms were first analyzed for filling time per quadrant. We then wrote a program to automatically compute focal flow fits for each macropixel and to detect convergent perilimbal flow patterns with macropixels grouped into 3 equal radial width rings around the cornea. A generalized additive model was used to determine fluorescence changes of individual macropixels. RESULTS: The resulting imaging algorithm deployed 1024 macropixels that were fit to determine maximum intensity and time to fill. These individual fits highlighted the focal flow function. In whole eyes, significantly faster flow was seen in the inferonasal (IN) and superonasal (SN) quadrants compared to the superotemporal (ST) and inferotemporal (IT) ones (p<0.05). In anterior chamber cultures, reduced flow on day 1 increased in all quadrants on day 3 except in IT (p<0.05). Perilimbal ring analysis uncovered convergent perilimbal flow. CONCLUSIONS: An algorithm was developed that analyzes regional and circumferential outflow patterns. This algorithm found flow patterns that changed over time and differ in whole eyes and anterior segment cultures. PMID- 26998836 TI - Are patients with hormonally functional phaeochromocytoma and paraganglioma initially receiving a proper adrenoceptor blockade? A retrospective cohort study. AB - OBJECTIVE: Pharmacological treatment is mandatory in patients with hormonally functional phaeochromocytoma and paraganglioma (PHAEO/PGL). We evaluated if patients initially diagnosed with hormonally functional PHAEO/PGL by various medical subspecialties received proper adrenoceptor blockade, and analysed factors predicting the prescription of adequate treatment. METHODS: In a retrospective cohort study, we reviewed data from patients initially diagnosed with hormonally functional PHAEO/PGL outside the National Institutes of Health and Cedars-Sinai Medical Center, who were referred to these institutions between January 2001 and April 2015. Logistic regression was used to assess factors associated with proper adrenoceptor blockade. RESULTS: A total of 381 patients were included. Adequate pharmacological treatment was prescribed to 69.3%, of which 93.1% received alpha-adrenoceptor blockers. Regarding patients who were inappropriately treated, 53% did not receive any medication. Independent predictors of the prescription of a proper blockade were the diagnosis by endocrinologists [odds ratio (OR) 4.14; 95% confidence interval (CI), 2.51-6.85; P < 0.001], the presence of high blood pressure (OR 5.94; 95% CI, 3.11-11.33; P < 0.001) and the evidence of metastasis (OR 5.96; 95% CI, 1.93-18.46; P = 0.002). CONCLUSIONS: Although most patients received adequate pharmacological treatment, almost one-third were either not treated or received inappropriate medications. The diagnosis by endocrinologists, the presence of high blood pressure and the evidence of metastatic disease were identified as independent predictors of a proper blockade. These results highlight the need to educate physicians about the importance of starting adequate adrenoceptor blockade in all patients with hormonally functional PHAEO/PGL. PMID- 26998835 TI - Modeling Smith-Lemli-Opitz syndrome with induced pluripotent stem cells reveals a causal role for Wnt/beta-catenin defects in neuronal cholesterol synthesis phenotypes. AB - Smith-Lemli-Opitz syndrome (SLOS) is a malformation disorder caused by mutations in DHCR7, which impair the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. SLOS results in cognitive impairment, behavioral abnormalities and nervous system defects, though neither affected cell types nor impaired signaling pathways are fully understood. Whether 7DHC accumulation or cholesterol loss is primarily responsible for disease pathogenesis is also unclear. Using induced pluripotent stem cells (iPSCs) from subjects with SLOS, we identified cellular defects that lead to precocious neuronal specification within SLOS derived neural progenitors. We also demonstrated that 7DHC accumulation, not cholesterol deficiency, is critical for SLOS-associated defects. We further identified downregulation of Wnt/beta-catenin signaling as a key initiator of aberrant SLOS iPSC differentiation through the direct inhibitory effects of 7DHC on the formation of an active Wnt receptor complex. Activation of canonical Wnt signaling prevented the neural phenotypes observed in SLOS iPSCs, suggesting that Wnt signaling may be a promising therapeutic target for SLOS. PMID- 26998834 TI - Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. AB - Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1 specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8(+) T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID- 26998838 TI - Effects of Central Corneal Stromal Thickness and Epithelial Thickness on Intraocular Pressure Using Goldmann Applanation and Non-Contact Tonometers. AB - PURPOSE: To investigate whether corneal thickness parameters measured by optical coherence tomography (OCT), such as central corneal thickness (CCT), central corneal stromal thickness (CCST), and central corneal epithelial thickness (CCET), influence the intraocular pressure (IOP) difference measured by Goldmann applanation tonometry (GAT) and non-contact tonometry (NCT). METHODS: In total, 50 eyes from 50 subjects without glaucomatous defects were included in this retrospective, cross-sectional study. We measured IOP using GAT and NCT and calculated the difference between the two methods. CCT was measured by a Cirrus HD-OCT device using anterior segment imaging. The basement membrane of the epithelium, which was seen as a high-reflection line in the OCT image, was taken as a reference line to measure CCST and CCET. RESULTS: The mean IOP measured by GAT and NCT was 16.7 +/- 3.0 and 18.1 +/- 3.8 mmHg, respectively. The mean IOP difference was 1.5 +/- 1.7 mmHg, and the IOP measured by NCT was 8.4% +/- 11.3% higher than that measured by GAT. The CCET and CCST were 57.9 +/- 5.6 and 501.7 +/- 33.8 MUm, respectively. CCT showed a positive correlation with both GAT IOP (r = 0.648, P < 0.001) and NCT IOP (r = 0.676, P < 0.001). Although CCST showed a significant correlation with GAT IOP and NCT IOP, CCET did not. The difference between GAT IOP and NCT IOP increased with CCT (r = 0.333, P = 0.018), and CCET was positively correlated with the IOP difference between GAT and NCT (r = 0.435, P = 0.002). CONCLUSIONS: IOP increased with greater CCT, and CCST seemed to have a more important role than CCET. CCET also increased with greater CCT, and this may be a possible explanation for the increasing difference in IOP between GAT and NCT with increasing CCT. PMID- 26998837 TI - MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells. AB - Airway smooth muscle (ASM) cells play a critical role in the pathophysiology of asthma due to their hypercontractility and their ability to proliferate and secrete inflammatory mediators. microRNAs (miRNAs) are gene regulators that control many signaling pathways and thus serve as potential therapeutic alternatives for many diseases. We have previously shown that miR-708 and miR-140 3p regulate the MAPK and PI3K signaling pathways in human ASM (HASM) cells following TNF-alpha exposure. In this study, we investigated the regulatory effect of these miRNAs on other asthma-related genes. Microarray analysis using the Illumina platform was performed with total RNA extracted from miR-708 (or control miR)-transfected HASM cells. Inhibition of candidate inflammation associated gene expression was further validated by qPCR and ELISA. The most significant biologic functions for the differentially expressed gene set included decreased inflammatory response, cytokine expression and signaling. qPCR revealed inhibition of expression of CCL11, CXCL10, CCL2 and CXCL8, while the release of CCL11 was inhibited in miR-708-transfected cells. Transfection of cells with miR 140-3p resulted in inhibition of expression of CCL11, CXCL12, CXCL10, CCL5 and CXCL8 and of TNF-alpha-induced CXCL12 release. In addition, expression of RARRES2, CD44 and ADAM33, genes known to contribute to the pathophysiology of asthma, were found to be inhibited in miR-708-transfected cells. These results demonstrate that miR-708 and miR-140-3p exert distinct effects on inflammation associated gene expression and biological function of ASM cells. Targeting these miRNA networks may provide a novel therapeutic mechanism to down-regulate airway inflammation and ASM proliferation in asthma. PMID- 26998840 TI - Correction: Evaluation of a Murine Single-Blood-Injection SAH Model. PMID- 26998839 TI - Identification and Analysis of Novel Viral and Host Dysregulated MicroRNAs in Variant Pseudorabies Virus-Infected PK15 Cells. AB - Pseudorabies (PR) is one of the most devastating diseases in the pig industry. To identify changes in microRNA (miRNA) expression and post-transcriptional regulatory responses to PRV infection in porcine kidney epithelial (PK15) cells, we sequenced a small RNA (sRNA) library prepared from infected PK15 cells and compared it to a library prepared from uninfected cells using Illumina deep sequencing. Here we found 25 novel viral miRNAs by high-throughput sequencing and 20 of these miRNAs were confirmed through stem-loop RT-qPCR. Intriguingly, unlike the usual miRNAs encoded by the alpha-herpesviruses, which are found clustered in the large latency transcript (LLT), these novel viral miRNAs are throughout the PRV genome like beta-herpesviruses. Viral miRNAs are predicted to target multiple genes and form a complex regulatory network. GO analysis on host targets of viral miRNAs were involved in complex cellular processes, including the metabolic pathway, biological regulation, stimulus response, signaling process and immune response. Moreover, 13 host miRNAs were expressed with significant difference after infection with PRV: 8 miRNAs were up-regulated and 5 miRNAs were down regulated, which may affect viral replication in host cell. Our results provided new insight into the characteristic of miRNAs in response to PRV infection, which is significant for further study of these miRNAs function. PMID- 26998841 TI - Alcohol-related deficient fracture healing is associated with activation of FoxO transcription factors in mice. AB - The process of fracture healing is complex, and poor or incomplete healing remains a significant health problem. Proper fracture healing relies upon resident mesenchymal stem cell (MSC) differentiation into chondrocytes and osteoblasts, which are necessary for callus formation and ossification. Alcohol abuse is a leading contributor to poor fracture healing. Although the mechanism behind this action is unknown, excessive alcohol consumption is known to promote systemic oxidative stress. The family of FoxO transcription factors is activated by oxidative stress, and FoxO activation antagonizes Wnt signaling, which regulates mesenchymal stem cell differentiation. We hypothesize that alcohol exposure increases oxidative stress leading to deficient fracture repair by activating FoxO transcription factors within the fracture callus which disrupts chondrogenesis of mesenchymal stem cells. Our laboratory has developed an experimental model of delayed fracture union in mice using ethanol administration. We have found that ethanol administration significantly decreases external, cartilaginous callus formation, and hallmarks of endochondral ossification, and these changes are concomitant with increases in FoxO expression and markers of activation in fracture callus tissue of these mice. We were able to prevent these alcohol-induced effects with the administration of the antioxidant n-acetyl cysteine (NAC), suggesting that alcohol-induced oxidative stress produces the perturbed endochondral ossification and FoxO expression. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2106-2115, 2016. PMID- 26998843 TI - In Response. PMID- 26998844 TI - Coumarin-Chalcone Hybrids as Peroxyl Radical Scavengers: Kinetics and Mechanisms. AB - The primary antioxidant activity of coumarin-chalcone hybrids has been investigated using the density functional and the conventional transition state theories. Their peroxyl radical scavenging ability was studied in solvents of different polarity and taking into account different reaction mechanisms. It was found that the activity of the hybrids increases with the polarity of the environment and the number of phenolic sites. In addition, their peroxyl radical scavenging activity is larger than those of the corresponding nonhybrid coumarin and chalcone molecules. This finding is in line with previous experimental evidence. All the investigated molecules were found to react faster than Trolox with (*)OOH, regardless of the polarity of the environment. The role of deprotonation on the overall activity of the studied compounds was assessed. The rate constants and branching ratios for the reactions of all the studied compounds with (*)OOH are reported for the first time. PMID- 26998842 TI - Quantitative Analysis of Axonal Branch Dynamics in the Developing Nervous System. AB - Branching is an important mechanism by which axons navigate to their targets during neural development. For instance, in the developing zebrafish retinotectal system, selective branching plays a critical role during both initial pathfinding and subsequent arborisation once the target zone has been reached. Here we show how quantitative methods can help extract new information from time-lapse imaging about the nature of the underlying branch dynamics. First, we introduce Dynamic Time Warping to this domain as a method for automatically matching branches between frames, replacing the effort required for manual matching. Second, we model branch dynamics as a birth-death process, i.e. a special case of a continuous-time Markov process. This reveals that the birth rate for branches from zebrafish retinotectal axons, as they navigate across the tectum, increased over time. We observed no significant change in the death rate for branches over this time period. However, blocking neuronal activity with TTX slightly increased the death rate, without a detectable change in the birth rate. Third, we show how the extraction of these rates allows computational simulations of branch dynamics whose statistics closely match the data. Together these results reveal new aspects of the biology of retinotectal pathfinding, and introduce computational techniques which are applicable to the study of axon branching more generally. PMID- 26998846 TI - Organ Transplantation in Nigeria. PMID- 26998845 TI - Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome. AB - OBJECTIVE: To establishing whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is superior primary debulking surgery (PDS) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer (AEOC) endowed with high tumour load (HTL). MATERIAL AND METHODS: This is a single-Institution, superiority, randomised phase III trial enrolling supposed AEOC women. Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index (PI) of tumour load. All AEOC women with PI>=8 or<=12 (considered as HTL) were included. They were randomly assigned (1:1 ratio) to undergo either PDS followed by systemic adjuvant chemotherapy (arm A, standard), or NACT followed by IDS (NACT/IDS) (arm B, experimental). Co-primary outcome measures were postoperative complications (graded according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system) and progression free survival (PFS); secondary outcomes were overall survival, and quality of life (QoL). QoL was assessed using the EORTC QoL questionnaires. A sample size of 110 patients was required for the analysis of the first co-primary end-point (major peri-operative morbidity) whereas recruitment is still on-going to achieve the statistical power on PFS. RESULTS: Between October 2011 and November 2014, we registered 280 AEOC. Of the 110 eligible women, 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery, rates of complete residual disease (residual tumour=0 cm) were superimposable between the groups (45.5% versus 57.7%; p=0.206). Twenty-nine patients (52.7%) in arm A experienced early grade III-IV complications versus three patients (5.7%) in IDS (p=0.0001). The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage (17/55 women (30.9%) in arm A versus 1/52 (1.9%) in arm B, p=0.0001). Three grade IV (5.4%) (i.e., two re-operations for postoperative haemorrhage and one septic multi-organ failure), and two grade V (3.6%) (two deaths for acute cardiopulmonary failure) early complications were observed in arm A only. Mean QoL scores of several scales/items were shown to ameliorate over time in both arms. Emotional functioning, cognitive functioning, nausea/vomiting, dyspnoea, insomnia and hair loss were statistically and clinically better in NACT/IDS compared to PDS arm. CONCLUSIONS: Perioperative moderate/severe morbidity as well as QoL scores were shown to be more favourable in NACT/IDS arm than PDS in AEOC patients with very HTL. Completion of patient enrolment and analysis of survival data will clarify whether PDS with such a high rate of severe complications is an acceptable treatment in AEOC women with HTL. PMID- 26998848 TI - A Novel Bioprosthetic Total Artificial Heart. PMID- 26998849 TI - Digital Learning in Transplantation. PMID- 26998851 TI - What We Learned From Plasma BK-Virus Monitoring in Allogeneic Hematopoietic Transplant Recipients. PMID- 26998850 TI - Attenuating Ischemia-Reperfusion Injury in Kidney Transplantation by Perfusing Donor Organs With siRNA Cocktail Solution. AB - BACKGROUND: Ischemia-reperfusion (I/R) injury is the major cause of delayed renal graft function in kidney transplantation. To date, there are no effective therapeutic approaches for preventing I/R injury. We previously reported that treatment of animals with small interference RNA (siRNA) would prevent warm I/R injury in nontransplant models and cold I/R injury in heart transplantation. In the present study, we further explore the feasibility of protecting grafts from extended cold I/R injury as applied to kidney transplantation by downregulating I/R-associated genes using siRNA. METHODS: Donor kidneys were intra-arterially perfused with siRNA containing solution during donor excision and preserved in siRNA containing solution. The siRNA-treated donor organs were then implanted into syngeneic recipient mice, and the 2 original kidneys were removed from the recipient. The effect of siRNA solution on extended cold I/R injury was determined by assessing renal function, histopathological change, cell apoptosis, and inflammation. RESULTS: The perfused siRNA solution knocked down the expression of complement 3, RelB, and Fas in the kidney at the mRNA and protein levels. Administration of siRNA solution reduced the levels of blood urea nitrogen and serum creatinine as compared with control groups. The siRNA cocktail decreased cell apoptosis and histopathological changes in the kidney and prolonged graft survival. The siRNA cocktail also reduced the expression of proinflammatory cytokines, IL-6, and TNFalpha. CONCLUSIONS: In conclusion, this is the first demonstration that perfusing donor organs with an siRNA cocktail solution can induce gene silencing in the kidney and prevent kidneys from extended cold I/R injury in kidney transplantation, highlighting the promise of the clinical application of siRNA-based therapies in the preservation of donor organs. PMID- 26998852 TI - Varicella Zoster Virus Vasculopathy After Kidney Transplantation. PMID- 26998853 TI - Donation After Cardiac Death Liver Transplantation After More Than 20 Minutes of Circulatory Arrest and Normothermic Regional Perfusion. PMID- 26998854 TI - Pharmacodynamics and pharmacokinetics of sodium zirconium cyclosilicate [ZS-9] in the treatment of hyperkalemia. AB - INTRODUCTION: Hyperkalemia is a common electrolyte disorder that arises from dysfunctional homeostatic mechanisms or as a consequence of decreased renal function. Sodium zirconium cyclosilicate (ZS-9) is a potential new therapy for hyperkalemia in both acute and chronic settings. AREAS COVERED: Here we discuss mechanisms of potassium homeostasis and preclinical and clinical studies that present pharmacokinetics/pharmacodynamics, efficacy and safety profiles of ZS-9. EXPERT OPINION: ZS-9 has a unique mechanism of action consisting of thermodynamically favorable sequestration of potassium ions, enabling rapid trapping and removal of excess potassium. The potassium lowering action of ZS-9 is predictable and rapid, leading to significant reduction of serum potassium within 1 hour of administration by irreversibly eliminating excess potassium rather than acting via intracellular translocation. Its safety profile, including gastrointestinal events, has been generally similar to that of placebo, with the exception of infrequent but manageable events of peripheral edema and transient hypokalemia. ZS-9 has demonstrated potential for enabling renin-angiotensin aldosterone system inhibitors in mid-term studies, with long-term studies ongoing. PMID- 26998855 TI - Niemann-Pick type C: focus on the adolescent/adult onset form. AB - Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment. PMID- 26998856 TI - Macroscopic and Microscopic Investigation of U(VI) and Eu(III) Adsorption on Carbonaceous Nanofibers. AB - The adsorption mechanism of U(VI) and Eu(III) on carbonaceous nanofibers (CNFs) was investigated using batch, IR, XPS, XANES, and EXAFS techniques. The pH dependent adsorption indicated that the adsorption of U(VI) on the CNFs was significantly higher than the adsorption of Eu(III) at pH < 7.0. The maximum adsorption capacity of the CNFs calculated from the Langmuir model at pH 4.5 and 298 K for U(VI) and Eu(III) were 125 and 91 mg/g, respectively. The CNFs displayed good recyclability and recoverability by regeneration experiments. Based on XPS and XANES analyses, the enrichment of U(VI) and Eu(III) was attributed to the abundant adsorption sites (e.g., -OH and -COOH groups) of the CNFs. IR analysis further demonstrated that -COOH groups were more responsible for U(VI) adsorption. In addition, the remarkable reducing agents of the R-CH2OH groups were responsible for the highly efficient adsorption of U(VI) on the CNFs. The adsorption mechanism of U(VI) on the CNFs at pH 4.5 was shifted from inner- to outer-sphere surface complexation with increasing initial concentration, whereas the surface (co)precipitate (i.e., schoepite) was observed at pH 7.0 by EXAFS spectra. The findings presented herein play an important role in the removal of radionuclides on inexpensive and available carbon-based nanoparticles in environmental cleanup applications. PMID- 26998857 TI - Sustainable efficient way for opioid peptide LVV-h7 preparation from enzymatic proteolysis in a microfluidic-based reaction-extraction process with solvent recycling. AB - LVV-h7 (LVVYPWTQFR) is a bioactive peptide that can be obtained from blood as waste of food industry, more precisely from hemoglobin hydrolysis by pepsin. This opioid peptide belongs to the hemorphins family and have strong physiological effects that bring its use in pharmaceutics and various therapeutic treatments attractive, in particular for substituting its costly chemically synthetized analogous. Hemoglobin hydrolysis by pepsin generates a huge variety of peptides among whose LVV-h7 can be purified by liquid-liquid extraction (LLE). Herein, selective preparation of this peptide is proposed by a microfluidic-based continuous reaction-separation process. Hemoglobin hydrolysis in microreactor was firstly coupled to LVV-h7 LLE in octan-1-ol and then coupled to LVV-h7 back LLE in acidic water. This continuous process allowed to prepare pure LVV-h7, as confirmed by liquid chromatography and mass spectrometry. The microfluidic circuit also allowed octan-1-ol recycling in a closed loop, making this method more sustainable than similar biphasic batch process. PMID- 26998858 TI - Sensitive detection of malachite green and crystal violet by nonlinear laser wave mixing and capillary electrophoresis. AB - An ultrasensitive label-free antibody-free detection method for malachite green and crystal violet is presented using nonlinear laser wave-mixing spectroscopy and capillary zone electrophoresis. Wave-mixing spectroscopy provides a sensitive absorption-based detection method for trace analytes. This is accomplished by forming dynamic gratings within a sample cell, which diffracts light to create a coherent laser-like signal beam with high optical efficiency and high signal-to noise ratio. A cubic dependence on laser power and square dependence on analyte concentration make wave mixing sensitive enough to detect molecules in their native form without the use of fluorescent labels for signal enhancement. A 532 nm laser and a 635 nm laser were used for malachite green and crystal violet sample excitation. The use of two lasers of different wavelengths allows the method to simultaneously detect both analytes. Selectivity is obtained through the capillary zone electrophoresis separation, which results in characteristic migration times. Measurement in capillary zone electrophoresis resulted in a limit of detection of 6.9 * 10(-10)M (2.5 * 10(-19) mol) for crystal violet and 8.3 * 10(-11)M (3.0 * 10(-20) mol) for malachite green at S/N of 2. PMID- 26998859 TI - Previous diagnosis of Sjogren's Syndrome as rheumatoid arthritis or systemic lupus erythematosus. AB - OBJECTIVE: The diagnosis of SS is often difficult and many patients are symptomatic for years with other diagnoses before confirmation of SS. Our aim was to determine whether overlapping clinical and serologic features with RA and SLE may in part drive the misdiagnoses. METHODS: A total of 1175 sicca patients were evaluated in a multidisciplinary clinic and classified as having SS based on the American-European Consensus Group Criteria. They were interrogated for a past history of suspicion or diagnosis of RA, SLE or SSc. These diseases were confirmed or ruled out by applying the corresponding classification criteria if the patients responded affirmatively. RESULTS: Of these, 524 (44.6%) subjects reported previous diagnosis or suspicion of RA, SLE or SSc, which was confirmed in 130 (24.8%) but excluded in 394 (75.2%) subjects. Of those previously diagnosed with another illness, 183 (34.9%) met the criteria for primary SS. RF was present in 70/191 patients with previous diagnosis of RA compared with 445/845 without a prior RA diagnosis (P = 3.38E-05), while 128/146 with a diagnosis of SLE had positive ANA compared with 622/881 without the diagnosis (P = 8.77E-06). Age also influenced former diagnoses: people with suspected RA were older than those without the diagnosis (P = 5.89E-06), while patients with SLE suspicion were younger (P = 0.0003). Interestingly, the previous diagnoses did not significantly delay a final classification of SS. CONCLUSION: Among subjects classified as SS, the presence of a positive ANA or RF was associated with a previous, apparently erroneous diagnosis of SLE or RA, respectively. PMID- 26998860 TI - Anti-TNF discontinuation and tapering strategies in patients with axial spondyloarthritis: a systematic literature review. AB - OBJECTIVE: The aim was to evaluate whether anti-TNF discontinuation and tapering strategies are efficacious for maintaining remission or low disease activity (LDA) in patients with axial spondyloarthritis. METHODS: A systematic literature review up to September 2014 was performed using Medline, EMBASE and Cochrane databases. Longitudinal studies evaluating the efficacy of discontinuation/tapering of anti-TNF therapy to maintain clinical response achieved after receiving a standard dose of the same drug were included. The results were grouped according to the type of strategy (discontinuation or tapering) evaluated. RESULTS: Thirteen studies out of 763 retrieved citations were included. Overall, published data are scarce and the level of evidence of the studies is weak. Five studies provided evidence for assessing discontinuation strategy. The frequency of patients developing flare during the follow-up period ranged between 76 and 100%. The median (range) follow-up period was 52 (36-52) weeks and time to flare 16 (6-24) weeks. Additionally, eight studies evaluating tapering strategy were selected. The percentage of patients maintaining LDA or remission was reported in five studies and ranged between 53 and 100%. The remaining three studies reported the mean change in BASDAI and CRP after reducing the anti-TNF dose and did not observe any relevant increase in these parameters. CONCLUSION: Published data indicate that a tapering strategy for anti-TNF therapy is successful in maintaining remission or LDA in most patients with axial spondyloarthritis. However, a discontinuation strategy is not recommended because it leads to flare in most cases. Further studies with an appropriate design covering the whole spectrum of the disease are required to confirm these results. PMID- 26998861 TI - Legionella: virulence factors and host response. AB - PURPOSE OF REVIEW: Legionella pneumophila is a facultative intracellular pathogen and an important cause of community-acquired and nosocomial pneumonia. This review focuses on the latest literature examining Legionella's virulence strategies and the mammalian host response. RECENT FINDINGS: Recent studies identify novel virulence strategies used by L. pneumophila and new aspects of the host immune response to this pathogen. Legionella prevents acidification of the phagosome by recruiting Rab1, a host protein. Legionella also blocks a conserved endoplasmic reticulum stress response. To access iron from host stores, L. pneumophila upregulates more regions allowing vacuolar colocalization N. In response to Legionella, the host cell may activate caspase-1, caspase-11 (mice) or caspase-4 (humans). Caspase-3 and apoptosis are activated by a secreted, bacterial effector. Infected cells send signals to their uninfected neighbors, allowing the elaboration of inflammatory cytokines in trans. Antibody subclasses provide robust protection against Legionella. SUMMARY: L. pneumophila is a significant human pathogen that lives in amoebae in the environment but may opportunistically infect the alveolar macrophage. To maintain its intracellular lifestyle, Legionella extracts essential iron from the cell, blocks inflammatory responses and manipulates trafficking to avoid fusion with the lysosome. The mammalian host has counter strategies, which include the release of proinflammatory cytokines, the activation of caspases and antibody-mediated immunity. PMID- 26998862 TI - Polycarboxylate ethers: The key towards non-toxic TiO2 nanoparticle stabilisation in physiological solutions. AB - Stable, non-agglomerated TiO2 nanoparticle (NP) dispersions are a crucial requirement for an accurate NP dosing in in vitro and in vivo experiments. In this study self-synthesised TiO2 NPs were stabilised in three different cell culture media (DMEM, RPMI, BEGM) with the help of stabilising agents. Cell culture tested stabilisers (bovine serum albumin, fetal bovine serum) were compared to non-tested commercial products which are commonly utilized in the cement industry (Melflux((r)) 4930 F, Melpers((r)) 4343, Sika((r)) ViscoCrete((r))-10110178). For a quantitative evaluation and comparison of the degree of stabilisation, a sedimentation study using UV absorbance spectroscopy was carried out and the agglomerate size was measured via dynamic light scattering. The cytotoxicity of the novel surfactants and stabilised NPs was examined in a head and neck squamous cell carcinoma-derived FaDu cell line and in human mesenchymal stem cells. We successfully stabilised TiO2 NPs with Melflux((r)) 4930 F in each cell culture medium, achieving perfect stability over at least one day and agglomerate sizes of less than 100nm, while the cytotoxicity of the NPs was not affected. PMID- 26998863 TI - Reengineered graft copolymers as a potential alternative for the bone tissue engineering application by inducing osteogenic markers expression and biocompatibility. AB - Composite scaffolds of nano-hydroxyapatite with demineralized bone matrix were prepared and they were graft copolymerized for better bone regeneration and drug delivery applications. The graft copolymers were characterized for their physiochemical properties using conventional methods like FTIR, TGA, XRD and SEM. The scaffolds were seeded with 3T3 and MG63 cells for studying their biocompatibility and their temporal expression of ALP activity, the rate of calcium deposition and their gene expression of collagen type I (Coll-1), osteopontin (OP), osteonectin (ON), and osteocalcin (OC) were studied. In vivo studies were conducted using sub-cutaneous implantation models in male Wister rats for 6 months. Periodic radiography and post-autopsy histopathology was analysed at 15days, 1, 2, 3, 4, 5, and 6 months. The obtained in vitro results clearly confirm that the bone scaffolds prepared in this study are biocompatible, superior osteoinductivity, capable of supporting growth, maturation of MG 63 osteoblast like cells; the gene expression profile revealed that the material is capable of supporting the in vitro growth and maturation of osteoblast-like cells and maturation. The in vivo results stand a testimony to the in vitro results in proving the biocompatibility and osteoinductivity of the materials. PMID- 26998864 TI - Preparation of HIFU-triggered tumor-targeted hyaluronic acid micelles for controlled drug release and enhanced cellular uptake. AB - In this study, a novel type of high intensity focused ultrasound (HIFU)-triggered active tumor-targeting polymeric micelle was prepared and investigated for controlled drug release and enhanced cellular uptake. Amphiphilic hyaluronic acid (HA) conjugates were synthesized to form docetaxel loaded micelles in aqueous conditions with high encapsulation efficiencies of over 80%. The micelle sizes were limited to less than 150nm, and they varied slightly according to the encapsulated drug amount. Modifying the micellar surface modification with polyethylene glycol diamine successfully inhibited premature drug leakage at a certain level, and it can be expected to prolong the circulation time of the particles in blood. In addition, high-intensity focused ultrasound was introduced to control the release of docetaxel from micelles, to which the release behavior of a drug can be tuned. The in-vitro cell cytotoxicity of docetaxel-loaded micelles was verified against CT-26 and MDA-MB-231 cells. The IC50 values of drug loaded micelles to CT-26 and MDA-MB-231 cells were 1230.2 and 870.9ng/mL, respectively. However, when exposed to HIFU, the values decreased significantly, to 181.9 and 114.3ng/mL, suggesting that HIFU can enhance cell cytotoxicity by triggering the release of a drug from the micelles. Furthermore, cellular uptake tests were conducted via the quantitative analysis of intracellular drug concentration within CT-26 (CD44 negative), MDA-MB-231 (CD44 positive), and MDA MB-231 (CD44 blocked), and then imaged with coumarin-6 loaded micelles. The results verified that intracellular drug delivery can be enhanced efficiently via the CD44 receptor-mediated endocytosis of HA micelles. Moreover, HIFU enhanced the cellular uptake behavior by altering the permeability of the cell membrane. It was also able to aid with the extravasation of micelles into the interior of tumors, which will be explained in further research. Therefore, the present study demonstrates that the micelles prepared in this study can emerge as promising nanocarriers of chemotherapeutic agents for controlled drug release and tumor targeting in cancer treatment. PMID- 26998865 TI - Cationized bovine serum albumin as gene carrier: Influence of specific secondary structure on DNA complexibility and gene transfection. AB - In this research, BSA, one of the natural rigid globular proteins with ca. 51% of alpha-helix secondary structure, was utilized to prepare cationized BSA (cBSA) as gene carrier. Tetraethylenepentamine (TEPA) or polyethylenimine (PEI1800) was grafted to BSA with different grafting levels. Based on the circular dichoism (CD) spectra, all cBSA remained alpha-helical structure to some degree. This was exciting to endow cBSA with quite different DNA complexibility and cellular biology behavior from the random coiled and flexible polycations such as PEI and poly-l-lysine (PLL). Strangely, the DNA condensability decreased with the increment of TEPA or PEI1800 grafting level. Also, the cBSA could condense DNA effectively to form irregular nanoparticles around 50-200nm above N/P ratio of 10. On account of the excellent hydration of BSA, the cBSA/DNA complexes revealed good colloidal stability under physiological salt condition. Cell culture experiments indicated this BSA-based gene carrier possessed good cellular compatibility. Surprisingly, cBSA/DNA complexes could be uptaken excellently by up to 90% cells. This might be owing to the agitation effect of alpha-helical structure and the positive potential of these complexes. BSA-PEI1800/DNA complexes with quick endosome escape even had transfection efficiency as high as PEI25k/DNA complexes. Overall, this paper provided us the potential of cBSA as gene carrier and might have some instructions in the design of protein-based gene delivery system. PMID- 26998866 TI - Degradation pattern of porous CaCO3 and hydroxyapatite microspheres in vitro and in vivo for potential application in bone tissue engineering. AB - Despite superior clinical handling, excellent biocompatibility, biodegradation property of calcium phosphate needs to be improved to coincide with the rate of new bone formation. In this study, spherical CaCO3 are fabricated in the presence of the silk sericin and then transformed into porous hydroxyapatite (HAP) microspheres via hydrothermal method. The degradation behavior of obtained CaCO3, HAP and their mixture is first investigated in vitro. The result demonstrates that the weight loss of HAP microspheres are almost 24.3% after immersing in pH 7.40 Tris-HCl buffer solution for 12 weeks, which is far slower than that of spherical CaCO3 (97.5%). The degradation speed of the mixtures depends on the proportion of CaCO3 and HAP. The mixture with higher content of CaCO3 possesses a quicker degradation speed. The obtained CaCO3 and HAP microspheres are injected into subcutaneous tissue of ICR mice with the assistance of sodium alginate. The result in vivo also shows an obvious difference of degradation speed between the obtained CaCO3 and HAP microspheres, implying it is feasible to modulate the degradation property of the mixture through changing the proportion of CaCO3 and HAP The good cytocompatibility of the two kinds of microspheres is proved and a mild inflammation response is observed only at early stage of implantation. The job offers a simple method to modify the degradation properties of biomaterial for potential use in bone tissue engineering. PMID- 26998868 TI - A novel biocompatible conducting polyvinyl alcohol (PVA)-polyvinylpyrrolidone (PVP)-hydroxyapatite (HAP) composite scaffolds for probable biological application. AB - We have prepared biocompatible composites of 80wt% polyvinyl alcohol (PVA) (20wt%) polyvinylpyrrolidone (PVP) blend with different concentrations of bioactive nanohydroxyapatite, Ca10(PO4)6(HO)2 (HAP). The composite films demonstrated maximum effective conductivity (sigma~1.64*10(-4)S/m) and effective dielectric constant (epsilon~290) at percolation threshold concentration (~10wt% HAP) at room temperature. These values of sigma and epsilon are much higher than those of PVA, PVP or HAP. Our preliminary observation indicated excellent biocompatibility of the electrospun fibrous meshes of two of these composites with different HAP contents (8.5 and 5wt% within percolation threshold concentration) using NIH 3T3 fibroblast cell line. Cells viability on the well characterized composite fibrous scaffolds was determined by MTT [3-(4,5-di methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay analysis. Enhancement of sigma, due to HAP addition, was found to show increased biocompatibility of the fibrous scaffold. Enhanced sigma value of the PVA/PVP-HAP composite provided supporting cues for the increased cell viability and biocompatibility of the composite fibrous meshes. Excellent biocompatibility these electrospun composite scaffolds made them to plausible potential candidates for tissue engineering or other biomedical applications. PMID- 26998867 TI - Diclofenac acid nanocrystals as an effective strategy to reduce in vivo skin inflammation by improving dermal drug bioavailability. AB - In this work a diclofenac acid nanosuspension formulation was produced as a novel approach for the treatment of skin inflammation. Drug nanocrystals, prepared by the wet media milling technique and stabilized using Poloxamer 188, were characterized by different techniques: scanning electron microscopy, differential scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared spectroscopy and photon correlation spectroscopy. The ability of nanocrystals to improve dermal drug bioavailability was investigated ex vivo by using Franz diffusion vertical cells and mouse skin, in comparison with both diclofenac acid coarse suspensions and a commercial formulation. The topical anti-inflammatory activity of the drug nanosuspension was assessed in vivo by testing its effect compared to common inflammatory endpoints: i.e. the inhibition of chemically induced oedema and leucocyte infiltration (reflected in myeloperoxidase activity). Following the milling procedure, diclofenac nanocrystals exhibited a mean diameter of approximately 279nm, a low polydispersity index (~0.17) and maintained the same polymorphic form of the starting bulk powder. When the drug nanosuspension was applied on the mouse skin it produced a higher accumulation of diclofenac in the skin compared to both the coarse suspensions and the commercial formulation, as demonstrated by ex vivo transdermal delivery experiments. Moreover, the nanosuspension provided an in vivo oedema inhibition of 50%, which was not statistically different from the commercial formulation. On the contrary, the nanosuspension showed a higher inhibition of myeloperoxidase activity in the damaged tissue (86%) than the commercial formulation (16%). PMID- 26998870 TI - Chitosan-clodronate nanoparticles loaded in poloxamer gel for intra-articular administration. AB - This work was based on the study of an intra-articular delivery system constituted by a poloxamer gel vehiculating clodronate in chitosan nanoparticles. This system has been conceived to obtain a specific and controlled release of clodronate in the joints to reduce the arthritis rheumatoid degenerative effect. Clodronate (CLO) is a first-generation bisphosphonate with anti-inflammatory properties, inhibiting the cytokine and NO secretion from macrophages, therefore causing apoptosis in these cells. This is related to its ability to be metabolized by cells and converted into a cytotoxic intermediate as a non hydrolysable analogue of ATP. Chitosan (CHI) was used to develop nanosystems, by ionotropic gelation induced by clodronate itself. A fractional factorial experimental design allowed us to obtain nanoparticles, the diameter of which ranged from 200 to 300nm. Glutaraldehyde was used to increase nanoparticle stability and modify the drug release profile. The zeta potential value of crosslinked nanopaparticles was 21.0mV+/-1.3, while drug loading was 31.0%+/-5.4 w/w; nanoparticle yield was 18.2%+/-1.8 w/w, the encapsulation efficiency was 48.8%+/-9.9 w/w. Nanoparticles were homogenously loaded in a poloxamer sol, and the drug delivery system is produced in-situ after local administration, when sol become gel at physiological temperature. The properties of poloxamer gels containing CHI-CLO nanoparticles, such as viscosity, gelation temperature and drug release properties, were evaluated. In vitro studies were conducted to evaluate the effects of these nanoparticles on a human monocytic cell line (THP1). The results showed that this drug delivery system is more efficient, with respect to the free drug, to counteract the inflammatory process characteristic of several degenerative diseases. PMID- 26998869 TI - Preparation of collagen/hydroxyapatite/alendronate hybrid hydrogels as potential scaffolds for bone regeneration. AB - Development of biomimetic scaffolds represents a promising direction in bone tissue engineering. In this study, we designed a two-step process to prepare a type of biomimetic hybrid hydrogels that were composed of collagen, hydroxyapatite (HAP) and alendronate (ALN), an anti-osteoporosis drug. First, water-soluble ALN-conjugated HAP (HAP-ALN) containing 4.0wt.% of ALN was synthesized by treating HAP particles with ALN. Hydrogels were then formed from HAP-ALN conjugate and collagen under physiological conditions using genipin (GNP) as the crosslinker. Depending on the ALN/collagen molar ratio and GNP concentration, the gelation time of hydrogels ranged from 5 to 37min. Notably, these hybrid hydrogels exhibited markedly improved mechanical property (storage modulus G'=38-187kPa), higher gel contents, and lower swelling ratios compared to the hydrogels prepared from collagen alone under similar conditions. Moreover, they showed tunable degradation behaviors against collagenase. The collagen/HAP ALN hybrid hydrogels supported the adhesion and growth of murine MC3T3-E1 osteoblastic cells well. Such tough yet enzymatically degradable hybrid hydrogels hold potential as scaffolds for bone tissue engineering. PMID- 26998871 TI - A new approach to produce drug nanosuspensions CO2-assisted effervescence to produce drug nanosuspensions. AB - The exploration of a simple and robust approach to produce nanosuspensions is a meaningful attempt for clinical translation. CO2-assisted effervescence was firstly developed to prepare nanosuspensions and was found to be easy for scale up. Drug nanosuspensions were easily obtained by adding aqueous carbonate to the pre-treated mixture of drug, stabilizer and organic acid. The burst of CO2 bubbles resulted from the acid-base reaction insert a micro gas bubble smashing and mixing effect to the formation of nanosuspensions, leading to smaller sizes and a refined size distribution. We successfully prepared nanosuspensions with twelve structurally diverse drugs. Alternatively, solid carbonate blended with the mixture, allowing for later addition of water, also facilitates the formation of amorphous nanosuspensions. We defined this approach as in situ nanoamorphization (ISN). Intensive in vitro and in vivo investigations for itraconazole and cabazitaxel nanosuspensions validate the availability for administration. PMID- 26998872 TI - Biocompatibility and degradation of gold-covered magneto-elastic biosensors exposed to cell culture. AB - Magneto-elastic materials (ME) have important advantages when applied as biosensors due to the possibility of wireless monitoring. Commercial Metglas 2826MB3TM (FeNiMoB) is widely used, however sensor stabilization is an important factor for biosensor performance. This study compared the effects of biocompatibility and degradation of the Metglas 2826MB3TM alloy, covered or not with a gold layer, when in contact with cell culture medium. Strips of amorphous Metglas 2826MB3TM were cut and coated with thin layers of Cr and Au, as verified by Rutherford Backscattering Spectroscopy (RBS). Using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), the presence of metals in the culture medium was quantitatively determined for up to seven days after alloy exposure. Biocompatibility of fibroblast Chinese Hamster Ovary (CHO) cultures was tested and cytotoxicity parameters were investigated by indirect means of reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) at 1, 2 and 7 days. Cell death was further evaluated through in situ analysis using Acridine Orange/Ethidium Bromide (AO/EB) staining and images were processed with ImageJ software. Ions from Metglas((r)) 2826MB3TM induced a degradation process in living organisms. The cytotoxicity assay showed a decrease in the percentage of live cells compared to control for the ME strip not coated with gold. AO/EB in situ staining revealed that most of the cells grown on top of the gold-covered sensor presented a normal morphology (85.46%). Covering ME sensors with a gold coating improved their effectiveness by generating protection of the transducer by reducing the release of ions and promoting a significant cell survival. PMID- 26998873 TI - Glycerol-regulated facile synthesis and targeted cell imaging of highly luminescent Ag2Te quantum dots with tunable near-infrared emission. AB - In this work, highly luminescent and emission tunable Ag2Te quantum dots (QDs) were facilely prepared by using water-dispersed glycerol as viscous solvent and CH3COOAg/Na2TeO3 as Ag/Te precursors. Viscous glycerol was utilized to slow the nucleation and growth of QDs at 200 degrees C, and enabled the isolation of QDs with different emission wavelengths. Experimental results revealed that the as prepared Ag2Te QDs exhibited tunable near-infrared emission from 930 to 1084nm, high photoluminescence (PL) quantum yields (QYs, more than 20%), good photostability and low cytotoxicity. After surface coating of a thin silica shell (~1.4nm), the resulting NH2 terminated Ag2Te@SiO2-NH2 displayed enhanced PL QYs, higher photostability and biocompatibility when compared with the original Ag2Te QDs. Through a facile carboxy-amine coupling, folic acid (FA) was grafted with Ag2Te@SiO2-NH2 to form Ag2Te@SiO2-FA nanocomposites, which were used for targeted PL imaging of folate receptor over-expressed tumor cells. PMID- 26998874 TI - The impact of auxins used in assisted phytoextraction of metals from the contaminated environment on the alterations caused by lead(II) ions in the organization of model lipid membranes. AB - Auxins are successfully used to improve phytoextraction efficiency of metal ions from the contaminated environment, however, the mechanism of their activity in this field is not explained. Auxins are known to exert various biochemical alterations in the plant membranes and cells, but their activity involves also direct interactions with lipids leading to changes in membrane organization. Following the suggestion that the auxins-induced modifications in membrane properties alleviate toxic effect of metal ions in this paper we have undertaken the comparative studies on the effect of metal ions and metal ions/auxins mixtures on model membrane systems. The experiments were done on lipid monolayers differing in their composition spread on water subphase and on Pb(2+), Indole-3 acetic acid (IAA), 1-Naphthaleneacetic acid (NAA) and Pb(2+)/IAA and Pb(2+)/NAA water solutions. The analysis of the collected data suggests that metal ions and auxins can change fluidity of the lipid systems and weaken the interactions between monolayer components. This manifested in the increase of the mean area per molecule and the excess area per molecule values for the films on Pb(2+), auxins as well as Pb(2+)/auxin solutions as compared to the values on pure water subphase. However, the presence of auxin in the mixture with lead(II) ions makes the alterations induced by sole metal ions weaker. This effect was more pronounced for the membranes of a higher packing. Thus it was proposed that auxins may enhance phytoextraction of metal ions by weakening their destabilizing effect on membrane. PMID- 26998875 TI - Intracellular interactions of electrostatically mediated layer-by-layer assembled polyelectrolytes based sorafenib nanoparticles in oral cancer cells. AB - In this paper, we report the preparation of LbL-nanoSraf (100-300nm) comprising of layer-by-layer (LbL) assembled polyelectrolytes dextran-sulfate/poly-l arginine, with a multikinase inhibitor sorafenib (Sraf) encapsulated calcium carbonate (CaCO3) nanoparticles for oral cancer therapy in vitro. The zeta potential of LbL-nanoSraf exhibited a negative charge of the polyanionic dextran sulfate, which alternated with a positive charge of polycationic poly-l-arginine indicating a successful LbL assembly of the two polyelectrolyte bilayers on the CaCO3 nanoparticles. The LbL-nanoSraf exhibited an encapsulation efficiency of 61+/-4%. The LbL-nanoSraf was characterized using field-emission gun scanning electron microscopy, X-ray powder diffraction, atomic force microscopy and confocal laser scanning microscopy. Confocal laser scanning microscopy, flow cytometry and transmission electron microscopic investigations showed the internalization of LbL-nanoSraf in human oral cancer (KB) cells. The LbL-nanoSraf exhibited more potent antiproliferative, apoptotic and antimigratory activities in KB cells than the free drug Sraf. The findings could promote the application of nano-sized LbL assembled polyelectrolytes for the delivery of Raf-kinase inhibitors and provide mechanistic insights for oral cancer therapy. PMID- 26998876 TI - Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials. AB - Bacterial resistance to antimicrobials is a global threat that requires development of innovative therapeutics that circumvent its onset. The use of Transcription Factor Decoys (TFDs), DNA fragments that act by blocking essential transcription factors in microbes, represents a very promising approach. TFDs require appropriate carriers to protect them from degradation in biological fluids and transfect them through the bacterial cell wall into the cytoplasm, their site of action. Here we report on a bolaform cationic surfactant, [12-bis THA]Cl2, with proven transfection activity in vivo. By studying the physical chemical properties of its aqueous solutions with light scattering, cryo-TEM, zeta-potential, absorption and fluorescence spectroscopies, we prove that the bolaamphiphiles associate into transient vesicles which convert into one dimensional elongated structures over time. These surfactant assemblies complex TFDs with extremely high efficiency, if compared to common cationic amphiphiles. At Z+/-=11, the nanoplexes are stable and have a size of 120nm, and they form independently of the original morphology of the [12-bis-THA]Cl2 aggregate. DNA is compacted in the nanoplexes, as shown through CD spectroscopy and fluorescence, but is readily released in its native form if sodium taurocholate is added. PMID- 26998877 TI - Reducing resistance to polio immunisation with free health camps and Bluetooth messaging: An update from Kaduna, Northern, Nigeria. AB - Since 1997, the Global Polio Eradication Initiative has sponsored regular door-to door polio immunisation campaigns in northern Nigeria. On 30 July 2015, the country was finally declared poliofree, a hard won success. At various times, polio eradication has been threatened by rumours and community tensions. For example, in 2003, local Imams, traditional leaders and politicians declared a polio campaign boycott, due to the concerns about the safety of the polio vaccine. Although the campaigns resumed in 2004, many parents continued to refuse vaccination because of the persistence of rumours of vaccine contamination, and anger about the poor state of health services for conditions other than polio. To address this, UNICEF and Nigerian Government partners piloted two interventions: (1) mobile 'health camps' to provide ambulatory care for conditions other than polio and (2) an audiovisual clip about vaccine safety and other health issues, shareable on multimedia mobile phones via Bluetooth pairing. The mobile phone survey found that Bluetooth compatible messages could rapidly spread behavioural health messages in low-literacy communities. The health camps roughly doubled polio vaccine uptake in the urban ward where it was piloted. This suggests that polio eradication would have been accelerated by improving primary health care services. PMID- 26998878 TI - Severe Mitral Regurgitation in Hypovolemic Shock Masquerading as Mitral Valve Perforation: A Rising Tide Lifts an Anchor. PMID- 26998879 TI - Potential Association Between Atrial Fibrillation and Dementia-Reply. PMID- 26998880 TI - Convergent validity and responsiveness of the EQ-5D utility weights for stroke survivors. AB - OBJECTIVE: This prospective study examined the convergent validity and responsiveness of the EuroQoL-5 Dimensions Health Questionnaire (EQ-5D) utility weights in stroke survivors at the subacute stage. METHODS: Repeated assessments were conducted in rehabilitation wards of a medical centre. A study cohort was recruited from inpatients (n = 478). A total of 342 participants (71.5%) completed 2 assessments; 1 at ward admission and 1 before hospital discharge. Outcome measures, including the Barthel Index (BI), Patient Health Questionnaire (PHQ-9) and EQ-5D, were administered at ward admission and before hospital discharge. RESULTS: The validity of the EQ-5D utility weights was assessed by comparison with the scores of the BI and PHQ-9. The absolute values of Pearson correlation coefficients ranged from 0.40 to 0.52 for the association of EQ-5D utility weights with BI scores and PHQ-9 scores at admission and before hospital discharge. The EQ-5D utility weights had a moderate effect size (0.76), moderate standardized response mean (0.74), and a significant difference (paired t-value = 13.7, p < 0.001) between baseline and follow-up in their ability to detect changes in the health status of stroke survivors staying in a rehabilitation ward. CONCLUSION: This study supports the use of the EQ-5D utility weights as a valid and responsive instrument for performing cost-utility analyses of stroke survivors, including those with higher levels of dependence, at the subacute stage. PMID- 26998881 TI - Toll-like receptors in hepatocellular carcinoma: potential novel targets for pharmacological intervention. AB - INTRODUCTION: Toll-like receptors (TLRs) are expressed by a wide variety of cell types including immune cells. They play a crucial role in the inflammatory and host defense response against microorganisms, and triggering TLRs can mediate the activation of innate immunity. Furthermore, research suggests that various TLRs may function differently on different tumor cells. The change in TLR activity may elicit an anti-tumor activity in hepatocellular carcinoma (HCC) cells and may serve as a novel therapeutic target for HCC therapy. AREAS COVERED: This review discusses the role of the TLR family in HCC and the underlying signaling pathway of TLRs as a form of pattern recognition receptor in mediating inflammation and HCC immunity responses. Agonists and antagonists of TLRs, which render TLRs as potential therapeutic targets, activate downstream molecules, subsequently causing HCC cell survival. The proliferation or protection against the development of HCC is also described. EXPERT OPINION: A series of studies have highlighted a crucial role of TLRs in HCC and consider TLR signaling pathways as potential therapeutic targets for HCC. However, the conclusions of these studies are in part paradoxical and controversial. Thus, it is necessary to extend further research to help determine the signaling pathways involved. PMID- 26998883 TI - Associative learning versus fear habituation as predictors of long-term extinction retention. AB - Violation of unconditioned stimulus (US) expectancy during extinction training may enhance associative learning and result in improved long-term extinction retention compared to within-session habituation. This experiment examines variation in US expectancy (i.e., expectancy violation) as a predictor of long term extinction retention. It also examines within-session habituation of fear potentiated startle (electromyography, EMG) and fear of conditioned stimuli (CS) throughout extinction training as predictors of extinction retention. Participants (n = 63) underwent fear conditioning, extinction and retention and provided continuous ratings of US expectancy and EMG, as well as CS fear ratings before and after each phase. Variation in US expectancy throughout extinction and habituation of EMG and fear was entered into a regression as predictors of retention and reinstatement of levels of expectancy and fear. Greater variation in US expectancy throughout extinction training was significantly predictive of enhanced extinction performance measured at retention test, although not after reinstatement test. Slope of EMG and CS fear during extinction did not predict retention of extinction. Within-session habituation of EMG and self-reported fear is not sufficient for long-term retention of extinction learning, and models emphasizing expectation violation may result in enhanced outcomes. PMID- 26998882 TI - Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis? AB - OBJECTIVES: To conduct a geographically defined, UK-based case-control study, to examine any association between physical activity (PA) and amyotrophic lateral sclerosis (ALS). METHODS: A novel historical PA questionnaire was designed, validated, and subsequently administered in individual face-to-face interviews of 175 newly diagnosed sporadic ALS cases and 317 age- and sex-matched community controls. Historical PA energy expenditure and time spent in vigorous-intensity PA were derived from questionnaire data and compared between cases and controls. RESULTS: Participation in an extra 10kJ/kg/day of PA (equivalent to approximately 45minutes brisk walking) was consistently associated with an increased risk of ALS, with the strongest association observed for adulthood exercise-related PA (OR 1.47, 95% CI 1.10-1.97). An extra 10mins/day of vigorous PA was also associated with the odds of ALS (OR 1.03, 95% CI 1.01-1.05). Results were slightly attenuated following adjustment for smoking and educational attainment. CONCLUSIONS: To our knowledge this is the first study to demonstrate a positive association between ALS and PA participation using a specifically designed and validated historical PA questionnaire. Despite the well-established health benefits of PA, a high activity lifestyle may also be associated with elevated risk of ALS. Large-scale prospective studies in the future may help to confirm this association. PMID- 26998884 TI - Soft-Tissue Sarcomas: An Update for Radiologists Based on the Revised 2013 World Health Organization Classification. AB - OBJECTIVE: Soft-tissue sarcomas are a diverse group of malignancies, and our rapidly improving understanding of their molecular pathogenesis and treatment is leading to better clinical outcomes. The revised 2013 World Health Organization (WHO) classification of soft-tissue sarcomas introduced several important changes. We provide a comprehensive overview of the relevant changes for radiologists. CONCLUSION: Rapid advances in the understanding of the pathogenesis and molecular biology of soft-tissue sarcomas led to major revisions in the 2013 WHO classification. To provide optimal multidisciplinary patient care, radiologists must remain up-to-date with the latest developments in the field of soft-tissue sarcomas to best correlate the histologic and imaging features of the various types of tumors and understand the unique patterns of treatment response and disease recurrence. PMID- 26998885 TI - Metabolite profiling of 14C-omacetaxine mepesuccinate in plasma and excreta of cancer patients. AB - Omacetaxine mepesuccinate (hereafter referred to as omacetaxine) is a protein translation inhibitor approved by the US Food and Drug Administration for adult patients with chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. The objective was to investigate the metabolite profile of omacetaxine in plasma, urine and faeces samples collected up to 72 h after a single 1.25-mg/m2 subcutaneous dose of 14C-omacetaxine in cancer patients. High-performance liquid chromatography mass spectrometry (MS) (high resolution) in combination with off-line radioactivity detection was used for metabolite identification. In total, six metabolites of omacetaxine were detected. The reactions represented were mepesuccinate ester hydrolysis, methyl ester hydrolysis, pyrocatechol conversion from the 1,3-dioxole ring. Unchanged omacetaxine was the most prominent omacetaxine-related compound in plasma. In urine, unchanged omacetaxine was also dominant, together with 4'-DMHHT. In feces very little unchanged omacetaxine was found and the pyrocatechol metabolite of omacetaxine, M534 and 4'-desmethyl homoharringtonine (4'-DMHHT) was the most abundant metabolites. Omacetaxine was extensively metabolized, with subsequent renal and hepatic elimination of the metabolites. The low levels of the metabolites found in plasma indicate that the metabolites are unlikely to contribute materially to the efficacy and/or toxicity of omacetaxine. PMID- 26998887 TI - Re: Robotic Partial Nephrectomy in the Treatment of Renal Angiomyolipomas (From: Kara O, Akca O, Zagar H, et al. J Endourol 2016;30:275-279). PMID- 26998886 TI - Contact force sensing during atrial fibrillation ablation: clinical experience and effects on outcomes. AB - Catheter ablation is an effective treatment option for atrial fibrillation (AF), and pulmonary vein isolation (PVI) is the cornerstone of AF ablation. When AF recurs after ablation, PV reconnection is frequently seen during repeat ablation. As such, achieving durable chronic PVI by delivering effective, transmural lesions during the index ablation is key to optimize long-term outcomes. The development of contact force (CF) sensing technologies integrated into ablation catheters now allow for real-time visualization of applied CF during PVI and have been shown to improve ablation efficacy and safety. The aim of this review is to describe the CF technology, summarize the literature on the outcomes of CF-guided ablation, and to discuss procedural aspects that are crucial when using CF. PMID- 26998888 TI - Carbon monoxide poisoning and pulmonary injury from the mixture of formic and sulfuric acids. AB - CONTEXT: The inhalation of carbon monoxide produced by the incomplete combustion of carbon remains a popular method of suicide. A much less common method of producing carbon monoxide for suicide is by mixing formic and sulfuric acids. CASE DETAILS: We describe a patient who attempted suicide by mixing formic and sulfuric acids. He presented with a depressed level of consciousness, chemical burns of his airway and skin, and respiratory distress. He was found to have a metabolic acidosis, a carboxyhemoglobin of 36.8%, hyperkalemia, and rhabdomyolysis. His hospital course was notable for copious pulmonary secretions and hypoxia, but he ultimately recovered with supportive care. DISCUSSION: The case highlights the potential toxicity, particularly from inhaled carbon monoxide and formic acid, with this method of suicide. PMID- 26998889 TI - Early risk factors for posterior crossbite and anterior open bite in the primary dentition. AB - OBJECTIVE: To investigate risk factors specific to posterior crossbite and anterior open bite at the age of 3 years. MATERIALS AND METHODS: The study included 422 children of the French EDEN mother-child cohort. The main outcomes were the presence of posterior crossbite and anterior open bite assessed by dentists at 3 years. Social characteristics (collected during pregnancy), neonatal characteristics (collected at birth), duration of breast-feeding (collected prospectively), sucking habits at 3 years, and open lips (as a proxy for mouth breathing) were studied and two logistic regressions conducted. RESULTS: Preterm birth appears to be a risk factor specific for posterior crossbite (OR: 3.13; 95% CI: 1.13-8.68), whereas small for gestational age seems to be associated with a lower risk of posterior crossbite (OR: 0.32; 95% CI: 0.12 0.87). Ongoing pacifier or thumb sucking at 3 years is a risk factor for both posterior crossbite and anterior open bite. CONCLUSIONS: Children born preterm seem to be more at risk for posterior crossbite than those born at term. Different mechanisms may be involved in posterior crossbite and anterior open bite. PMID- 26998890 TI - On the principle of host evolution in host-pathogen interactions. AB - In this paper, we use a two-host one pathogen immuno-epidemiological model to argue that the principle for host evolution, when the host is subjected to a fatal disease, is minimization of the case fatality proportion [Formula: see text]. This principle is valid whether the disease is chronic or leads to recovery. In the case of continuum of hosts, stratified by their immune response stimulation rate a, we suggest that [Formula: see text] has a minimum because a trade-off exists between virulence to the host induced by the pathogen and virulence induced by the immune response. We find that the minimization of the case fatality proportion is an evolutionary stable strategy for the host. PMID- 26998891 TI - Blood on the tracks - toward precision medicine. PMID- 26998892 TI - Voltage clustering in redox-active ligand complexes: mitigating electronic communication through choice of metal ion. AB - The redox-active bis(imino)acenapthene (BIAN) ligand was used to synthesize homoleptic aluminum, chromium, and gallium complexes of the general formula (BIAN)3M. The resulting compounds were characterized using X-ray crystallography, NMR, EPR, magnetic susceptibility and cyclic voltammetry measurements and modeled using both DFT and ab initio wavefunction calculations to compare the orbital contributions of main group elements and transition metals in ligand-based redox events. Complexes of this type have the potential to improve the energy density and electrolyte stability of grid-scale energy storage technologies, such as redox flow batteries, through thermodynamically-clustered redox events. PMID- 26998893 TI - Synergy of Two Assembly Languages in DNA Nanostructures: Self-Assembly of Sequence-Defined Polymers on DNA Cages. AB - DNA base-pairing is the central interaction in DNA assembly. However, this simple four-letter (A-T and G-C) language makes it difficult to create complex structures without using a large number of DNA strands of different sequences. Inspired by protein folding, we introduce hydrophobic interactions to expand the assembly language of DNA nanotechnology. To achieve this, DNA cages of different geometries are combined with sequence-defined polymers containing long alkyl and oligoethylene glycol repeat units. Anisotropic decoration of hydrophobic polymers on one face of the cage leads to hydrophobically driven formation of quantized aggregates of DNA cages, where polymer length determines the cage aggregation number. Hydrophobic chains decorated on both faces of the cage can undergo an intrascaffold "handshake" to generate DNA-micelle cages, which have increased structural stability and assembly cooperativity, and can encapsulate small molecules. The polymer sequence order can control the interaction between hydrophobic blocks, leading to unprecedented "doughnut-shaped" DNA cage-ring structures. We thus demonstrate that new structural and functional modes in DNA nanostructures can emerge from the synergy of two interactions, providing an attractive approach to develop protein-inspired assembly modules in DNA nanotechnology. PMID- 26998894 TI - Evaluating the psychometric properties of the Interpersonal Needs Questionnaire and the Acquired Capability for Suicide Scale in military veterans. AB - Joiner's (2005) interpersonal-psychological theory of suicide (IPTS) has become one of the most frequently studied in the field. Currently there are 2 primary measures designed to assess the 3 main constructs of the theory-the Interpersonal Needs Questionnaire (INQ; Van Orden, Witte, Gordon, Bender, & Joiner, 2008) and the Acquired Capability for Suicide Scale (ACSS; Van Orden et al., 2008). The psychometric properties of these 2 measures were evaluated in a sample of 477 U.S. military veterans. It was determined that the factor structure for both measures is consistent with the underlying theory and that all internal consistency reliability estimates are good. Acceptable convergent validity was found for the INQ, but not for the ACSS. Recommendations for refining the ACSS based on the results of the current analyses are provided. Comparisons of scale performance were made with data from participants with and without a history of 1 or more suicide attempts. Burdensomeness alone and the interaction between thwarted belongingness and burdensomeness were associated with prior suicide attempts. In conclusion, although some refinement may improve performance of the ACSS, both measures are appropriate and psychometrically sound for use in research and clinical applications with veterans of the U.S. military. (PsycINFO Database Record PMID- 26998895 TI - Fabrication of Mesoporous Silica Nanoparticle with Well-Defined Multicompartment Structure as Efficient Drug Carrier for Cancer Therapy in Vitro and in Vivo. AB - Vaterite particles are composed of particulate CaCO3 nanoparticles, which offer an ideal platform to synthesize architectures with hierarchical structure. Herein we show that mesoporous silica particles with well-defined multicompartment structure are fabricated by employing vaterite particles as templates. The obtained silica particles inherited the structure feature of vaterite and had excellent biocompatibility and biodegradability. Moreover, the silica particles were established as an efficient anticancer drugs carrier compared with hollow silica particles, which could be applied in cancer therapy in vitro and in vivo. The silica particles obtained here offer a cheap, facile, environmentally friendly avenue to assembly of hierarchical drugs carriers. PMID- 26998896 TI - Graphene-Based Microbots for Toxic Heavy Metal Removal and Recovery from Water. AB - Heavy metal contamination in water is a serious risk to the public health and other life forms on earth. Current research in nanotechnology is developing new nanosystems and nanomaterials for the fast and efficient removal of pollutants and heavy metals from water. Here, we report graphene oxide-based microbots (GOx microbots) as active self-propelled systems for the capture, transfer, and removal of a heavy metal (i.e., lead) and its subsequent recovery for recycling purposes. Microbots' structure consists of nanosized multilayers of graphene oxide, nickel, and platinum, providing different functionalities. The outer layer of graphene oxide captures lead on the surface, and the inner layer of platinum functions as the engine decomposing hydrogen peroxide fuel for self-propulsion, while the middle layer of nickel enables external magnetic control of the microbots. Mobile GOx-microbots remove lead 10 times more efficiently than nonmotile GOx-microbots, cleaning water from 1000 ppb down to below 50 ppb in 60 min. Furthermore, after chemical detachment of lead from the surface of GOx microbots, the microbots can be reused. Finally, we demonstrate the magnetic control of the GOx-microbots inside a microfluidic system as a proof-of-concept for automatic microbots-based system to remove and recover heavy metals. PMID- 26998897 TI - Whole-exome sequencing of duodenal adenocarcinoma identifies recurrent Wnt/beta catenin signaling pathway mutations. AB - BACKGROUND: Genomic alterations of small bowel cancers remain poorly understood due to the rarity of these diseases. In the current study, the authors report the identification of somatic mutations from patients with duodenal adenocarcinoma by whole-exome sequencing. METHODS: Whole-exome sequencing and follow-up analysis were conducted in 12 matched tumor-normal tissue duodenal adenocarcinoma tissue pairs to examine the genetic characteristics of this disease. Somatic mutations (single-nucleotide variants and short insertion/deletions) were obtained and filtered and then searched for recurrently mutated genes and pathways. RESULTS: An excess of C-to-T transitions at the CpG dinucleotide was observed in the substitution of bases. The authors identified recurrent mutations in tumor protein p53 (TP53), KRAS, catenin (cadherin-associated protein) beta-1 (CTNNB1), AT-rich interactive domain 2 (ARID2), adenomatous polyposis coli (APC), erb-b2 receptor tyrosine kinase 2 (ERBB2), ARID1A, cadherin-related family member 1 (CDHR1), NRAS, Bcl-2-related ovarian killer (BOK), radial spoke head 14 homolog (chlamydomonas) (RTDR1), cell division cycle 27 (CDC27), catalytic subunit of phosphoinositide-3-kinase (PIK3CA), and SMAD family member 4 (SMAD4). Pathway scan indicated that the Wnt signaling pathway, regulation of the actin cytoskeleton pathway, ErbB signaling pathway, and the pathway of focal adhesion were the most extensively affected pathways. CONCLUSIONS: This genomic characterization of duodenal adenocarcinoma provides researchers with insight into its somatic landscape and highlights the vital role of the Wnt/beta-catenin signaling pathway. The study data also indicate that duodenal adenocarcinomas have a genetic resemblance to gastric and colorectal cancers. These discoveries may benefit the future development of molecular diagnosis and personalized therapies. Cancer 2016;122:1689-96. (c) 2016 American Cancer Society. PMID- 26998898 TI - Carnosic Acid-combined Arsenic Trioxide Antileukaemia Cells in the Establishment of NB4/SCID Mouse Model. AB - Despite great improvement in the treatment outcome of APL, treatment failure still sometimes occurs due to the toxicity of arsenic trioxide (ATO). Damage to the heart and liver often occurs even when the dose is lower than the therapeutic dose. Based on the results of cell experiments in vitro in this study, we investigated the synergistic activity of carnosic acid (CA) combined with ATO in the SCID mouse model of human promyelocytic leukaemia in vivo. A NB4/SCID mouse model was established in this study. The NB4/SCID mice were randomly divided into three treatment groups (CA alone, ATO alone and CA combined with ATO) and a control group based on factorial design. The evaluation indicators of the curative effect of the drugs included expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins by immunohistochemistry, flow cytometry and Western blot analysis. The survival time was compared between the four groups. The results indicated that verification of the NB4/SCID mouse model was confirmed by histopathological examination. Compared with mice treated by CA or ATO alone, the mice in the combination of CA and ATO group had a higher rate of apoptosis, which was linked with expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins. Also, the mice with the longest survival time were those treated with the combination of CA and ATO. In conclusion, the results of the present study indicated that CA and ATO in combination have strong synergistic antileukaemic effects on cell activity. PMID- 26998899 TI - Rapid prototyping of electrochemical lateral flow devices: stencilled electrodes. AB - A straightforward and very cost effective method is proposed to prototype electrodes using pressure sensitive adhesives (PSA) and a simple cutting technique. Two cutting methods, namely blade cutting and CO2 laser ablation, are compared and their respective merits are discussed. The proposed method consists of turning the protective liner on the adhesive into a stencil to apply screen printing pastes. After the electrodes have been printed, the liner is removed and the PSA can be used as a backing material for standard lateral flow membranes. We present the fabrication of band electrodes down to 250 MUm wide, and their characterization using microscopy techniques and cyclic voltammetry. The prototyping approach presented here facilitates the development of new electrochemical devices even if very limited fabrication resources are available. Here we demonstrate the fabrication of a simple lateral-flow device capable of determining glucose in blood. The prototyping approach presented here is highly suitable for the development of novel electroanalytical tools. PMID- 26998900 TI - Label-free fluorescence detection of microRNA based on target induced adenosine2 coralyne-adenosine2 formation. AB - This study develops a simple and label-free biosensor for sensitive and selective detection of microRNA (miRNA) based on the formation of the adenosine2-coralyne adenosine2 complex mediated by miRNA-specific polyadenosine extension. PMID- 26998901 TI - Early Prediction of Hypertensive Disorders of Pregnancy Using Cell-Free Fetal DNA, Cell-Free Total DNA, and Biochemical Markers. AB - OBJECTIVE: To evaluate the predictive value of separate and combined tests using cell-free fetal DNA (cffDNA), cell-free total DNA (cfDNA), and biochemical markers for the early detection of pregnancies with hypertensive disorders. METHODS: A nested case-control study was conducted with 135 singleton pregnancies including 17 gestational hypertension cases, 34 preeclampsia (PE) cases, and 84 controls. We performed real-time quantitative PCR to measure levels of DSCR3 and RASSF1A as cffDNA markers and HYP2 as a cfDNA marker in the first and early second trimesters. Levels of pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein, beta-human chorionic gonadotropin, unconjugated estriol, and inhibin A were also determined. RESULTS: Compared with controls, the median levels and multiples of the median (MoM) values of HYP2 were significantly higher in the PE and hypertensive disorders of pregnancy (HDP) groups at 6-14 and 15-23 weeks. Frist-trimester PAPP-A MoM was significantly lower in PE and HDP than in controls. For PE and HDP, the best model included the first-trimester DSCR3, HYP2, and PAPP-A MoM values achieving detection rates of 67 and 58% at a fixed 10% false-positive rate, respectively [area under the receiver operating characteristic curve 0.832 (95% CI 0.689-0.928) for PE; 0.751 (0.607-0.863) for HDP]. DISCUSSION: The study demonstrates the potential utility of combined first trimester cffDNA, cfDNA, and PAPP-A for the early prediction of PE. PMID- 26998903 TI - Hemodynamic responses to single sessions of aerobic exercise and resistance exercise in pregnancy. AB - INTRODUCTION: Previous research on maternal hemodynamic responses to a single exercise session during pregnancy is sparse, especially considering immediate responses to resistance exercise. The aim of the study was to examine blood pressure, heart rate, body temperature, and Rating of Perceived Exertion in healthy pregnant women during single sessions of continuous submaximal exercise in pregnancy week 21. MATERIAL AND METHODS: A cross-over design was used. Twenty healthy pregnant women from four prenatal clinics in Gothenburg, Sweden, were included. On day 1, the women did 30 min of aerobic exercise and on day 3 they did 30 min of resistance exercise. Blood pressure, heart rate, and Rating of Perceived Exertion were measured after 15 and 30 min of exercise. RESULTS: After 15 and 30 min of exercise, there was a significant increase in systolic blood pressure and heart rate (p < 0.001). Diastolic blood pressure increased slightly more after 15 and 30 min of aerobic exercise (p = 0.01) than resistance exercise (p = 0.03). Resistance exercise was perceived as more intense than aerobic exercise after 15 min (p = 0.02) and 30 min (p = 0.001) of exercise. Five minutes after completing the exercise, blood pressure quickly reverted to normal although heart rate was still increased (p = 0.001). There was no correlation between heart rate and Rating of Perceived Exertion (rs = 0.05-0.43). CONCLUSIONS: Maternal hemodynamic responses were essentially the same, regardless of whether the exercise was submaximal aerobic or resistance exercise, although resistance exercise was perceived as more intense. Aerobic and resistance exercise corresponding to "somewhat hard" seems to have no adverse effect with regard to maternal hemodynamic responses in healthy pregnancy. PMID- 26998902 TI - Enhanced Diabetes Susceptibility in Community Dwelling Han Elders Carrying the Apolipoprotein E 3/3 Genotype. AB - Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE epsilon2 group (epsilon2/epsilon2 and epsilon2/epsilon3), APOE epsilon3 group (epsilon3/epsilon3), and APOE epsilon4 group (epsilon2/epsilon4, epsilon3/epsilon4 and epsilon4/epsilon4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE epsilon3/epsilon3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE epsilon3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE epsilon2 and APOE epsilon4 groups (P<0.05). The APOE epsilon3 group had slightly higher abnormal fasting plasma glucose values than did the APOE epsilon2 group (P = 0.065). Furthermore, the APOE3 genotype was significantly correlated with both fasting plasma glucose level and glucose abnormality (P< 0.05) and trended toward statistically significant correlation with diabetes (P = 0.082). The correlation between APOE2 and low low-density lipoprotein levels also approached statistical significance (P = 0.052). Thus, elderly community dwelling residents of Han ethnicity carrying the APOE epsilon3/epsilon3 genotype might have higher plasma glucose levels and a higher occurrence of diabetes. PMID- 26998904 TI - Low-Risk Prostate Cancer and Tumor Upgrading to Higher Patterns in the Surgical Specimen. Analysis of Clinical Factors Predicting Tumor Upgrading to Higher Gleason Patterns in a Contemporary Series of Patients Who Have Been Evaluated According to the Modified Gleason Score Grading System. AB - OBJECTIVE: To identify clinical factors associated with prostate cancer (PCA) upgrading to higher patterns of the surgical specimen in low-risk PCA. MATERIALS AND METHODS: We evaluated the records of 438 patients. The multinomial logistic regression model was used. RESULTS: Low-risk PCA included 170 cases (38.8%) and tumor upgrading was detected in 111 patients (65.3%) of whom 72 (42.4%) had pathological Gleason patterns (pGP) = 3 + 4 and 39 (22.9%) pGP >3 + 4. Prostate specific antigen (PSA) and proportion of positive cores (P+) were independent predictors of tumor upgrading to higher patterns. The main difference between upgraded cancers related to PSA and to P+ >0.20. The population was stratified into risk classes by PSA <=5 MUg/l and P+ <=0.20 (class A), PSA >5 MUg/l and P+ <=0.20 (class B), PSA <=5 MUg/l and P+ >0.20 (class C) and PSA >5 MUg/l and P+ 0.20 (class D). Upgrading rates to pGP >3 + 4 were extremely low in class A (5.1%), extremely high in D (53.8%). CONCLUSIONS: Low-risk PCA is a heterogeneous population with significant rates of undetected high-grade disease. Significant clinical predictors of upgrading to higher patterns include PSA and P+, which identify a very high-risk class that needs repeat biopsies in order to reclassify tumor grade. PMID- 26998905 TI - Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years. AB - BACKGROUND AND PURPOSE: The long-term benefit of natalizumab on brain atrophy progression in multiple sclerosis (MS) patients is unknown. Our aim was to investigate its effect over 5 years. METHODS: This prospective study included 60 relapsing MS patients who started natalizumab treatment in years 2006-2007. RESULTS: At the 5-year follow-up, 20 patients discontinued natalizumab after an average of 29.5 cycles, 27 continued natalizumab treatment with some periods of honeymoon (average of 38.4 infusions) and 13 never stopped natalizumab (average of 60.6 infusions). In multiple linear regression analysis, adjusted for age, sex and baseline magnetic resonance imaging (MRI) status, the number of natalizumab infusions was associated with decrease of relapse rate (adjusted P = 0.037), but no association was found with the progression of disability, accumulation of lesion burden or brain volume loss. However, only one (8%) patient in the continuous monthly group experienced disability progression compared to 10 (37%) in the non-continuous and seven (35%) in the discontinuation natalizumab groups. At the follow-up, two patients had died [one from a fatal case of progressive multifocal leukoencephalopathy (PML) and one from a car accident] and 15 patients were lost to follow-up. There was another case of non-fatal PML over the follow up. CONCLUSIONS: In line with previous reports, MS patients with longer and continuous use of natalizumab had fewer relapses and remained stable in their disability status. No difference in lesion burden accumulation or brain atrophy development was found in relation to the duration of natalizumab use. PML occurred in 2.5% of patients in this small sample cohort. Given the increased risk of PML and uncertain benefit of prolonged natalizumab use on clinical and MRI outcomes of disease progression found in this study, a careful risk-benefit therapeutic assessment is mandatory. PMID- 26998908 TI - Dual Fluorescence in GFP Chromophore Analogues: Chemical Modulation of Charge Transfer and Proton Transfer Bands. AB - Dual fluorescence of GFP chromophore analogues has been observed for the first time. OHIM (o-hydroxy imidazolidinone) shows only a charge transfer (CT) band, CHBDI (p-cyclicamino o-hydroxy benzimidazolidinone) shows a comparable intensity CT and PT (proton transfer) band, and MHBDI (p-methoxy o-hydroxy benzimidazolidinone) shows a higher intensity PT band. It could be shown that the differential optical behavior is not due to conformational variation in the solid or solution phase. Rather, control of the excited state electronic energy level and excited state acidity constant by functional group modification could be shown to be responsible for the differential optical behavior. Chemical modification-induced electronic control over the relative intensity of the charge transfer and proton transfer bands could thus be evidenced. Support from single crystal X-ray structure, NMR, femtosecond to nanosecond fluorescence decay analysis, and TDDFT-based calculation provided important information and thus helped us understand the photophysics better. PMID- 26998906 TI - Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice. AB - Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC), the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis. PMID- 26998907 TI - Melanin fate in the human epidermis: a reassessment of how best to detect and analyse histologically. AB - Melanin is the predominant pigment responsible for skin colour and is synthesized by the melanocyte in the basal layer of the epidermis and then transferred to surrounding keratinocytes. Despite its optical properties, melanin is barely detectable in unstained sections of human epidermis. However, identification and localization of melanin is of importance for the study of skin pigmentation in health and disease. Current methods for the histologic quantification of melanin are suboptimal and are associated with significant risk of misinterpretation. The aim of this study was to reassess the existing literature and to develop a more effective histological method of melanin quantification in human skin. Moreover, we confirm that Warthin-Starry (WS) stain provides a much more sensitive and more specific melanin detection method than the commonplace Fontana-Masson (FM) stain. For example, WS staining sensitivity allowed the visualization of melanin even in very pale Caucasian skin that was missed by FM or Von Kossa (VK) stains. From our reassessment of the histology-related literature, we conclude that so-called melanin dust is most likely an artifact of discoloration due to non-specific silver deposition in the stratum corneum. Unlike FM and VK, WS was not associated with this non-specific stratum corneum darkening, misinterpreted previously as 'degraded' melanin. Finally, WS melanin particle counts were largely similar to previously reported manual counts by transmission electron microscopy, in contrast to both FM and VK. Together these findings allow us to propose a new histology/Image J-informed method for the accurate and precise quantification of epidermal melanin in skin. PMID- 26998909 TI - [Minimally invasive interventional techniques involving the urogenital tract in dogs and cats]. AB - Minimally invasive interventional techniques are advancing fast in small animal medicine. These techniques utilize state-of-the-art diagnostic methods, including fluoroscopy, ultrasonography, endoscopy, and laparoscopy. Minimally invasive procedures are particularly attractive in the field of small animal urology because, in the past, treatment options for diseases of the urogenital tract were rather limited or associated with a high rate of complications. Most endourological interventions have a steep learning curve. With the appropriate equipment and practical training some of these procedures can be performed in most veterinary practices. However, most interventions require referral to a specialty clinic. This article summarizes the standard endourological equipment and materials as well as the different endourological interventions performed in dogs and cats with diseases of the kidneys/renal pelves, ureters, or lower urinary tract (urinary bladder and urethra). PMID- 26998910 TI - Predictive roles of gut dysbiosis on the severity of nonalcoholic fatty liver disease. PMID- 26998911 TI - Germination sensitivity to water stress in four shrubby species across the Mediterranean Basin. AB - Mediterranean shrublands are generally water-limited and fire-driven ecosystems. Seed-based post-fire regeneration may be affected by varying rainfall patterns, depending on species sensitivity to germinate under water stress. In our study, we considered the germination response to water stress in four species from several sites across the Mediterranean Basin. Seeds of species with a hard coat (Cistus monspeliensis, C. salviifolius, Cistaceae, Calicotome villosa, Fabaceae) or soft coat (Erica arborea, Ericaceae), which were exposed or not to a heat shock and smoke (fire cues), were made to germinate under water stress. Final germination percentage, germination speed and viability of seeds were recorded. Germination was modelled using hydrotime analysis and correlated to the water balance characteristics of seed provenance. Water stress was found to decrease final germination in the three hard-seeded species, as well as reduce germination speed. Moreover, an interaction between fire cues and water stress was found, whereby fire cues increased sensitivity to water stress. Seed viability after germination under water stress also declined in two hard-seeded species. Conversely, E. arborea showed little sensitivity to water stress, independent of fire cues. Germination responses varied among populations of all species, and hydrotime parameters were not correlated to site water balance, except in E. arborea when not exposed to fire cues. In conclusion, the species studied differed in germination sensitivity to water stress; furthermore, fire cues increased this sensitivity in the three hard-seeded species, but not in E. arborea. Moreover, populations within species consistently differed among themselves, but these differences could only be related to the provenance locality in E. arborea in seeds not exposed to fire cues. PMID- 26998912 TI - Low-Pressure Cobalt-Catalyzed Enantioselective Hydrovinylation of Vinylarenes. AB - An efficient and practical protocol for the enantioselective cobalt-catalyzed hydrovinylation of vinylarenes with ethylene at low (1.2 bar) pressure has been developed. As precatalysts, stable [L2 CoCl2 ] complexes are employed that are activated in situ with Et2 AlCl. A modular chiral TADDOL-derived phosphine phosphite ligand was identified that allows the conversion of a broad spectrum of substrates, including heterocyclic vinylarenes and vinylferrocene, to smoothly afford the branched products with up to 99 % ee and virtually complete regioselectivity. Even polar functional groups, such as OH, NH2 , CN, and CO2 R, are tolerated. PMID- 26998913 TI - Identification by FFPE RNA-Seq of a new recurrent inversion leading to RBM10-TFE3 fusion in renal cell carcinoma with subtle TFE3 break-apart FISH pattern. AB - Gene fusions involving TFE3 defines the "Xp11.2 translocations" subclass of renal cell carcinomas (RCCs) belonging to the MiT family translocation RCC. Four recurrent TFE3 fusion partners were identified to date: PRCC, ASPSCR1, SFPQ, and NONO. Break-apart TFE3 fluorescence in situ hybridization (FISH) on formalin fixed and paraffin-embedded (FFPE) tissue sections is currently the gold standard for identification of TFE3 rearrangements. Herein, we report a case of RCC with a morphological appearance of Xp11.2 translocation, and positive TFE3 immunostaining. By FISH, the spots constituting the split signal were barely spaced, suggestive of a chromosome X inversion rather than a translocation. We performed RNA-seq from FFPE material to test this hypothesis. RNA-seq suggested a fusion of RBM10 gene exon 17 (Xp11.23) with TFE3 gene exon 5 (Xp11.2). RBM10-TFE3 fusion transcript was confirmed using specific RT-PCR. Our work showed that RNA Seq is a robust technique to detect fusion transcripts from FFPE material. A RBM10-TFE3 fusion was previously described in single case of Xp11.2 RCC. Although rare, RBM10-TFE3 fusion variant (from chromosome X paracentric inversion), therefore, appears to be a recurrent molecular event in Xp11.2 RCCs. RBM10-TFE3 fusion should be added in the list of screened fusion transcripts in targeted molecular diagnostic multiplex RT-PCR. (c) 2016 Wiley Periodicals, Inc. PMID- 26998914 TI - Kinetics of the self-assembly of nanocrystal superlattices measured by real-time in situ X-ray scattering. AB - On solvent evaporation, non-interacting monodisperse colloidal particles self assemble into a close-packed superlattice. Although the initial and final states can be readily characterized, little is known about the dynamic transformation from colloid to superlattice. Here, by using in situ grazing-incidence X-ray scattering, we tracked the self-assembly of lead sulfide nanocrystals in real time. Following the first appearance of an ordered arrangement, the superlattice underwent uniaxial contraction and collective rotation as it approached its final body-centred cubic structure. The nanocrystals became crystallographically aligned early in the overall self-assembly process, showing that nanocrystal ordering occurs on a faster timescale than superlattice densification. Our findings demonstrate that synchrotron X-ray scattering is a viable method for studying self-assembly in its native environment, with ample time resolution to extract kinetic rates and observe intermediate configurations. The method could be used for real-time direction of self-assembly processes and to better understand the forces governing self-organization of soft materials. PMID- 26998915 TI - Observation of Aubry-type transition in finite atom chains via friction. AB - The highly nonlinear many-body physics of a chain of mutually interacting atoms in contact with a periodic substrate gives rise to complex static and dynamical phenomena, such as structural phase transitions and friction. In the limit of an infinite chain incommensurate with the substrate, Aubry predicted a transition with increasing substrate potential, from the chain's intrinsic arrangement free to slide on the substrate, to a pinned arrangement favouring the substrate pattern. So far, the Aubry transition has not been observed. Here, using spatially resolved position and friction measurements of cold trapped ions in an optical lattice, we observed a finite version of the Aubry transition and the onset of its hallmark fractal atomic arrangement. Notably, the observed critical lattice depth for few-ion chains agrees well with the infinite-chain prediction. Our results elucidate the connection between competing ordering patterns and superlubricity in nanocontacts-the elementary building blocks of friction. PMID- 26998916 TI - Morphology selection via geometric frustration in chiral filament bundles. AB - In assemblies, the geometric frustration of a locally preferred packing motif leads to anomalous behaviours, from self-limiting growth to defects in the ground state. Here, we demonstrate that geometric frustration selects the equilibrium morphology of cohesive bundles of chiral filaments, an assembly motif critical to a broad range of biological and synthetic nanomaterials. Frustration of inter filament spacing leads to optimal shapes of self-twisting bundles that break the symmetries of packing and of the underlying inter-filament forces, paralleling a morphological instability in spherical two-dimensional crystals. Equilibrium bundle morphology is controlled by a parameter that characterizes the relative costs of filament bending and the straining of cohesive bonds between filaments. This parameter delineates the boundaries between stable, isotropic cylindrical bundles and anisotropic, twisted-tape bundles. We also show how the mechanical and interaction properties of constituent amyloid fibrils may be extracted from the mesoscale dimensions of the anisotropic bundles that they form. PMID- 26998917 TI - Long-Term Effects of an Extensive Cognitive Training on Personality Development. AB - Previous research found that cognitive training increases the Big Five personality trait Openness to Experience during and some weeks after the intervention. The present study investigated whether long-term changes happen in Openness to Experience and other personality traits after an extensive cognitive training of memory and perceptual speed. The intervention group consisted of 204 adults (20-31 years and 65-80 years; 50% female) who received daily 1-hour cognitive training sessions for about 100 days. The control group consisted of 86 adults (21-29 years and 65-82 years; 51% female) who received no cognitive training. All participants answered the NEO Five-Factor Inventory before and 2 years after the cognitive training. Latent change models were applied that controlled for age group (young vs. old) and gender. In the long run, the cognitive training did not affect changes in any facet of Openness to Experience. This was true for young and old participants as well as for men and women. Instead, the cognitive training lowered the general increase of Conscientiousness. Even an extensive cognitive training on memory and perceptual speed does not serve as a sufficient intervention for enduring changes in Openness to Experiences or one of its facets. PMID- 26998920 TI - Inverse Electron-Demand [4 + 2]-Cycloadditions of Ynamides: Access to Novel Pyridine Scaffolds. AB - Functionalized polycyclic aminopyridines are central to the chemical sciences, but their syntheses are still hampered by a number of shortcomings. These nitrogenated heterocycles can be efficiently prepared by an intramolecular inverse electron demand hetero Diels-Alder (ihDA) cycloaddition of ynamides to pyrimidines. This ihDA/rDA sequence is general in scope and affords expedient access to novel types of aminopyridinyl scaffolds that hold great promise in terms of exit vector patterns. PMID- 26998919 TI - Pathogenesis of the antiphospholipid syndrome revisited: time to challenge the dogma. AB - For more than a decade the antiphospholipid syndrome (APS) has been reported to be caused mainly by antiphospholipid antibodies (aPL), which are not directed against phospholipids but against a complex of phospholipids and phospholipid binding proteins, so called cofactors (e.g. beta2-glycoprotein I [beta2GPI]). In fact, many researchers propose that the only relevant antigens in the APS are the cofactors themselves, with beta2GPI being the most important. Antibodies that bind to phospholipids in a cofactor-independent manner are considered insignificant for the pathogenesis of the APS. We review the evidence for this current pathophysiologic concept and argue that it has never been proven and is now clearly no longer tenable. First, there is undisputable evidence that cofactor-independent aPL are pathogenic and present in the blood of APS patients. Second, available epidemiologic and clinical studies do not support a dominant pathogenic role for anti-beta2GPI. PMID- 26998918 TI - Merging Two Strategies for Mixed-Sequence Recognition of Double-Stranded DNA: Pseudocomplementary Invader Probes. AB - The development of molecular strategies that enable recognition of specific double-stranded DNA (dsDNA) regions has been a longstanding goal as evidenced by the emergence of triplex-forming oligonucleotides, peptide nucleic acids (PNAs), minor groove binding polyamides, and--more recently--engineered proteins such as CRISPR/Cas9. Despite this progress, an unmet need remains for simple hybridization-based probes that recognize specific mixed-sequence dsDNA regions under physiological conditions. Herein, we introduce pseudocomplementary Invader probes as a step in this direction. These double-stranded probes are chimeras between pseudocomplementary DNA (pcDNA) and Invader probes, which are activated for mixed-sequence dsDNA-recognition through the introduction of pseudocomplementary base pairs comprised of 2-thiothymine and 2,6-diaminopurine, and +1 interstrand zipper arrangements of intercalator-functionalized nucleotides, respectively. We demonstrate that certain pseudocomplementary Invader probe designs result in very efficient and specific recognition of model dsDNA targets in buffers of high ionic strength. These chimeric probes, therefore, present themselves as a promising strategy for mixed-sequence recognition of dsDNA targets for applications in molecular biology and nucleic acid diagnostics. PMID- 26998921 TI - A quantitative study of tau pathology in 11 cases of chronic traumatic encephalopathy. AB - AIMS: To quantify tau pathology of chronic traumatic encephalopathy (CTE) and investigate influence of dot-like lesions (DL), brain region, comorbidity and sporting career length. METHODS: Densities of neurofibrillary tangles (NFT), astrocytic tangles (AT), DL, oligodendroglial inclusions (GI), neuropil threads (NT), vacuoles, neurons and enlarged neurons (EN) were measured in tau immunoreactive sections of upper cortical laminae of frontal and temporal lobes, hippocampus (HC), amygdala and substantia nigra (SN) in 11 cases of CTE. RESULTS: DL were a consistent finding in CTE. Densities of NFT, NT and DL were greatest in sectors CA1 and CA2 of the HC. Densities of AT were lower than NFT, small numbers of GI were recorded in temporal lobe and low densities of vacuoles and EN were consistently present. beta-Amyloid-containing neuritic plaques (NP) also occurred at low density. Densities of NFT, NT, DL and AT were greater in sulci than gyri, while vacuole density was greater in gyri. Principal components analysis (PCA) suggested that sporting career length and densities of NFT in entorhinal cortex, NT in CA2 and SN and vacuolation in the DG were significant sources of variation among cases. CONCLUSION: DL are frequent in CTE suggesting affinity with argyrophilic grain disease (AGD) and Parkinson's disease dementia (PD-Dem). Densities of AT in all regions and NT/DL in sectors CA2/4 were consistent features of CTE. The 11 cases are neuropathologically heterogeneous which may result from genetic diversity, and variation in anatomical pathways subjected to trauma. PMID- 26998922 TI - Healthcare professionals approach paediatric fever in significantly different ways and fever phobia is not just limited to parents. AB - AIM: Fever is a benign process, but it is still frequently regarded as harmful. We aimed to evaluate the knowledge of parents and healthcare professionals on fever. METHODS: Data were obtained through questionnaires administered to a sample of parents and nurses in the paediatric emergency rooms of two hospitals and to family doctors and paediatricians currently practising in Portugal. RESULTS: We collected 265 answers from parents, 49 from nurses and 525 from doctors. Most nurses (74%), doctors (55%) and parents (43%) considered fever as a temperature above 38 degrees C. The parents' first reaction to a febrile child was to give them antipyretics, and acetaminophen was used most frequently (44%). Nurses considered that a child with fever must always be treated and that a history of febrile seizures was the most decisive factor in initiating treatment. On the other hand, the most important factor for paediatricians was the presence of discomfort. For parents (74%) and nurses (92%), the most feared effect of untreated fever was seizures, and for paediatricians (97%), it was irritability. CONCLUSION: The parents' and nurses' attitudes demonstrated fear of fever and its consequences. The approach to paediatric fever was significantly different among healthcare professionals. PMID- 26998923 TI - View-Invariant Visuomotor Processing in Computational Mirror Neuron System for Humanoid. AB - Mirror neurons are visuo-motor neurons found in primates and thought to be significant for imitation learning. The proposition that mirror neurons result from associative learning while the neonate observes his own actions has received noteworthy empirical support. Self-exploration is regarded as a procedure by which infants become perceptually observant to their own body and engage in a perceptual communication with themselves. We assume that crude sense of self is the prerequisite for social interaction. However, the contribution of mirror neurons in encoding the perspective from which the motor acts of others are seen have not been addressed in relation to humanoid robots. In this paper we present a computational model for development of mirror neuron system for humanoid based on the hypothesis that infants acquire MNS by sensorimotor associative learning through self-exploration capable of sustaining early imitation skills. The purpose of our proposed model is to take into account the view-dependency of neurons as a probable outcome of the associative connectivity between motor and visual information. In our experiment, a humanoid robot stands in front of a mirror (represented through self-image using camera) in order to obtain the associative relationship between his own motor generated actions and his own visual body-image. In the learning process the network first forms mapping from each motor representation onto visual representation from the self-exploratory perspective. Afterwards, the representation of the motor commands is learned to be associated with all possible visual perspectives. The complete architecture was evaluated by simulation experiments performed on DARwIn-OP humanoid robot. PMID- 26998924 TI - The Role of Lumbar Sympathetic Nerves in Regulation of Blood Flow to Skeletal Muscle during Anaphylactic Hypotension in Anesthetized Rats. AB - During hypovolemic shock, skeletal muscle blood flow could be redistributed to vital organs via vasoconstriction in part evoked by activation of the innervating sympathetic nerve activity. However, it is not well known whether this mechanism operates during anaphylactic shock. We determined the femoral artery blood flow (FBF) and lumbar sympathetic nerve activity (LSNA) mainly regulating the hindquater muscle blood flow during anaphylactic hypotension in anesthetized rats. Anesthetized Sprague-Dawley rats were randomly allocated to the following groups (n = 7/group): (1) non-sensitized, (2) anaphylaxis, (3) anaphylaxis-lumbar sympathectomy (LS) and (4) anaphylaxis-sinoaortic denervation (SAD) groups. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen to the sensitized rats. The systemic arterial pressure (SAP), heart rate (HR), central venous pressure (CVP), FBF and LSNA were continuously measured. In the anaphylaxis group, LSNA and HR increased, while SAP and FBF decreased after antigen injection. In the anaphylaxis-SAD group, LSNA did not significantly change during the early phase, but the responses of SAP and FBF were similar to those in the anaphylaxis group. In the anaphylaxis-LS group, both FBF and SAP decreased similarly to the anaphylaxis group during anaphylactic hypotension. These results indicated that LSNA increased via baroreceptor reflex, but this sympathoexcitation or LS did not affect antigen-induced decreases in FBF or SAP. Lumbar sympathetic nerves are not involved in regulation of the blood flow to the hindlimb or systemic blood pressure during anaphylactic hypotension in anesthetized rats. PMID- 26998926 TI - VFFDT: A New Software for Preparing AMBER Force Field Parameters for Metal Containing Molecular Systems. AB - Force fields are fundamental to molecular dynamics simulations. However, the incompleteness of force field parameters has been a long-standing problem, especially for metal-related systems. In our previous work, we adopted the Seminario method based on the Hessian matrix to systematically derive the zinc related force field parameters for AMBER. In this work, in order to further simplify the whole protocol, we have implemented a user-friendly Visual Force Field Derivation Toolkit (VFFDT) to derive the force field parameters via simply clicking on the bond or angle in the 3D viewer, and we have further extended our previous program to support the Hessian matrix output from a variety of quantum mechanics (QM) packages, including Gaussian 03/09, ORCA 3.0, QChem, GAMESS-US, and MOPAC 2009/2012. In this toolkit, a universal VFFDT XYZ file format containing the raw Hessian matrix is available for all of the QM packages, and an instant force field parametrization protocol based on a semiempirical quantum mechanics (SQM) method is introduced. The new function that can automatically obtain the relevant parameters for zinc, copper, iron, etc., which can be exported in AMBER Frcmod format, has been added. Furthermore, our VFFDT program can read and write files in AMBER Prepc, AMBER Frcmod, and AMBER Mol2 format and can also be used to customize, view, copy, and paste the force field parameters in the context of the 3D viewer, which provides utilities complementary to ANTECHAMBER, MCPB, and MCPB.py in the AmberTools. PMID- 26998925 TI - Functional Activity of Antibodies Directed towards Flagellin Proteins of Non Typhoidal Salmonella. AB - Non-typhoidal Salmonella (NTS) serovars Typhimurium and Enteritidis are major causes of invasive bacterial infections in children under 5 years old in sub Saharan Africa, with case fatality rates of ~20%. There are no licensed NTS vaccines for humans. Vaccines that induce antibodies against a Salmonella Typhi surface antigen, Vi polysaccharide, significantly protect humans against typhoid fever, establishing that immune responses to Salmonella surface antigens can be protective. Flagella proteins, abundant surface antigens in Salmonella serovars that cause human disease, are also powerful immunogens, but the functional capacity of elicited anti-flagellar antibodies and their role in facilitating bacterial clearance has been unclear. We examined the ability of anti-flagellar antibodies to mediate microbial killing by immune system components in-vitro and assessed their role in protecting mice against invasive Salmonella infection. Polyclonal (hyperimmune sera) and monoclonal antibodies raised against phase 1 flagellin proteins of S. Enteritidis and S. Typhimurium facilitated bacterial uptake and killing of the homologous serovar pathogen by phagocytes. Polyclonal anti-flagellar antibodies accompanied by complement also achieved direct bacterial killing. Serum bactericidal activity was restricted to Salmonella serovars expressing the same flagellin used as immunogen. Notably, individual anti-flagellin monoclonal antibodies with complement were not bactericidal, but this biological activity was restored when different monoclonal anti-flagellin antibodies were combined. Passive transfer immunization with a monoclonal IgG antibody specific for phase 1 flagellin from S. Typhimurium protected mice against lethal challenge with a representative African invasive S. Typhimurium strain. These findings have relevance for the use of flagellin proteins in NTS vaccines, and confirm the role of anti-flagellin antibodies as mediators of protective immunity. PMID- 26998927 TI - Use of Indirect Calorimetry to Detect Overfeeding in Critically Ill Children: Finding the Appropriate Definition. AB - OBJECTIVES: Overfeeding during critical illness is associated with adverse effects such as metabolic disturbances and increased risk of infection. Because of the lack of sound studies with clinical endpoints, overfeeding is arbitrarily defined as the ratio caloric intake/measured resting energy expenditure (mREE) or alternatively as a comparison of measured respiratory quotient (RQ) to the predicted RQ based on the macronutrient intake (RQmacr). We aimed to compare definitions of overfeeding in critically ill mechanically ventilated children based on mREE, RQ, and caloric intake to find an appropriate definition. METHODS: Indirect calorimetry measurements were performed in 78 mechanically ventilated children, median age 6.3 months. Enteral and/or parenteral nutrition was provided according to the local guidelines. Definitions used to indicate overfeeding were the ratio caloric intake/mREE of >110% and >120% and by the measured RQ > RQmacr + 0.05. RESULTS: The proportion of patients identified as overfed varied widely depending on the definition used, ranging from 22% (RQ > RQmacr + 0.05), to 40% and 50% (caloric intake/mREE of >120% and >110%, respectively). Linear regression analysis showed that all patients would be identified as overfed with the definition RQ > RQmacr + 0.05 when the ratio caloric intake/mREE exceeded 165%. Caloric intake was higher in children with a standard deviation-score weight for age <-2. CONCLUSIONS: The proportion of mechanically ventilated patients identified as overfed ranged widely depending on the definition applied. These currently used definitions fail to take into account several relevant factors affecting metabolism during critical illness and are therefore not generally applicable to the pediatric intensive care unit population. PMID- 26998929 TI - Correction: Threshold Games and Cooperation on Multiplayer Graphs. PMID- 26998928 TI - Self-Reported Empathy in Adult Women with Autism Spectrum Disorders - A Systematic Mini Review. AB - INTRODUCTION: There is limited research on Autism Spectrum Disorders (ASD) in females. Although the empathy construct has been examined thoroughly in autism, little attention has been paid to empathy in adult women with this condition or to gender differences within the disorder. OBJECTIVE: Self-reported empathy in adult women with ASD was examined and compared to that of typically developed men and women as well as to men with this condition. METHODS: Online databases were searched for articles investigating self-reported empathy among adult women with ASD. Only six studies comparing women to men were identified. RESULTS: All studies found women with an ASD to report lower levels of empathy than typically developed women, and typically developed men, but similar levels to men with this condition. CONCLUSION: The self-reported empathic ability of women diagnosed with ASD resembles that of their male counterparts most closely; they show a hypermasculinisation in empathy. This is particularly surprising considering the large gender difference in empathy in the general population. DISCUSSION: One of the limitations of this review is that the current diagnostic criteria for ASD are oriented towards male-specific behaviour and fail to integrate gender specific characteristics. Hence, women diagnosed with ASD are likely to be at the male end of the continuum. The suggested hypermasculinisation of women on the spectrum, as evident from this review, may therefore be exaggerated due to a selection bias. PMID- 26998930 TI - Breast Involvement in Pure Cutaneous Rosai-Dorfman Disease: Ultrasound and Sonoelastography Appearance With a Review of the Literature. AB - Rosai-Dorfman disease or sinus histiocytosis of the lymph nodes is a rare, idiopathic, and benign disorder. Painless lymphadenopathy is the most frequent systemic presenting symptom and involves the cervical region in up to 90% of the patients. Extranodal involvement is less common and can represent the initial or the only presentation of the disease. We present the ultrasound and sonoelastographic features of a case of extranodal, pure cutaneous Rosai-Dorfman disease involving the breast, in which the breast involvement led to the final diagnosis. We discuss the ultrasound appearance of the disease (on B-mode, Doppler ultrasound, and sonoelastography) with a review of the literature and the different morphological patterns encountered in extranodal and cutaneous involvement. PMID- 26998934 TI - Recent advancements in diagnostic tools in mitochondrial energy metabolism diseases. AB - The involvement of mitochondrial energy metabolism in human disease ranges from rare monogenic disease to common diseases and aging with a genetic and/or lifestyle/environmental cause. This wide ranging involvement is due to the central role played by mitochondrion in cellular metabolism, its role in cellular perception of threats and its role in effecting responses to these threats. Investigating mitochondrial function/dysfunction or mitochondria-associated cell biological responses have thus become a common finding where the pathogenic processes are investigated. Although, such investigations are warranted, it is not always clear if mitochondria can indeed be associated with cause or merely playing a responsive role in disease pathology. As this key question is also essential to disease progression and therapy, it should be recognized in investigative design. We herewith, present an overview of the current approaches and technologies used and the practicalities around these technologies. PMID- 26998933 TI - A New Fiji-Based Algorithm That Systematically Quantifies Nine Synaptic Parameters Provides Insights into Drosophila NMJ Morphometry. AB - The morphology of synapses is of central interest in neuroscience because of the intimate relation with synaptic efficacy. Two decades of gene manipulation studies in different animal models have revealed a repertoire of molecules that contribute to synapse development. However, since such studies often assessed only one, or at best a few, morphological features at a given synapse, it remained unaddressed how different structural aspects relate to one another. Furthermore, such focused and sometimes only qualitative approaches likely left many of the more subtle players unnoticed. Here, we present the image analysis algorithm 'Drosophila_NMJ_Morphometrics', available as a Fiji-compatible macro, for quantitative, accurate and objective synapse morphometry of the Drosophila larval neuromuscular junction (NMJ), a well-established glutamatergic model synapse. We developed this methodology for semi-automated multiparametric analyses of NMJ terminals immunolabeled for the commonly used markers Dlg1 and Brp and showed that it also works for Hrp, Csp and Syt. We demonstrate that gender, genetic background and identity of abdominal body segment consistently and significantly contribute to variability in our data, suggesting that controlling for these parameters is important to minimize variability in quantitative analyses. Correlation and principal component analyses (PCA) were performed to investigate which morphometric parameters are inter-dependent and which ones are regulated rather independently. Based on nine acquired parameters, we identified five morphometric groups: NMJ size, geometry, muscle size, number of NMJ islands and number of active zones. Based on our finding that the parameters of the first two principal components hardly correlated with each other, we suggest that different molecular processes underlie these two morphometric groups. Our study sets the stage for systems morphometry approaches at the well-studied Drosophila NMJ. PMID- 26998935 TI - Transvaginal Laparoscopically Assisted Endoscopic Appendectomy: a major Hybrid Natural Orifice Transluminal Endoscopic Surgery case series in Asia. AB - OBJECTIVE: Evaluation of a Hybrid Approach to NOTES and its performance relative to conventional procedures. BACKGROUND: Globally, numerous institutions have successfully implemented minimally invasive surgeries by applying natural orifice translumenal endoscopic surgery (NOTES) techniques and achieved decreased morbidity while performing incision-less surgery. However, these techniques are still not common in surgical practice in China and Pakistan. Documenting the experiences and challenges encountered in implementing NOTES in such environments can provide guidance for NOTES implementation elsewhere. METHODS: From May 2010 to April 2012, 16 human transvaginal appendectomies were carried out applying a hybrid NOTES technique using a solo-umbilical trocar, which provided a safe access for laparoscopic assistance during surgical procedure. After removal of the appendix transvaginally, the colpotomy was sutured under direct vision with absorbable stitches. The outcomes of cases treated with hybrid NOTES techniques were compared to those of conventional laparoscopic appendectomy. RESULTS: All patients underwent a successful surgical procedure with no intra- or post operative complications and provided no specific complaints during the tenth day and a monthly follow-up for 2 years. The patients convalesced promptly with healthy and satisfactory cosmetic results. Compared to conventional laparoscopic appendectomy, the hybrid NOTES operation had less post-operative pain, lower cost, and shorter hospitalization. CONCLUSIONS: Hybrid NOTES procedures can be performed safely using a solo-umbilical trocar. Our initial experience reveals that this hybrid technique is practically feasible and associated with minimal post-operative pain, reasonable convalescence time, and improved cosmetic outcomes. PMID- 26998936 TI - ABC transporters at the blood-brain barrier. AB - INTRODUCTION: The blood-brain barrier (BBB) possesses an outstanding ability to protect the brain against xenobiotics and potentially poisonous metabolites. Owing to this, ATP binding cassette (ABC) export proteins have garnered significant interest in the research community. These transport proteins are predominantly localized to the luminal membrane of brain microvessels, where they recognize a wide range of different substrates and transport them back into the blood circulation. AREAS COVERED: This review summarizes recent findings on these transport proteins, including their expression in the endothelial cell membrane and their substrate recognition. Signaling cascades underlying the expression and function of these proteins will be discussed as well as their role in diseases such as Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis and brain tumors. EXPERT OPINION: ABC transporters represent an integral part of the human transportome and are of particular interest at the blood-brain barrier they as they significantly contribute to brain homeostasis. In addition, they appear to be involved in myriad CNS diseases. Therefore studying their mechanisms of action as well as their signaling cascades and responses to internal and external stimuli will help us understand the pathogenesis of these diseases. PMID- 26998937 TI - Bayesian Maximum Entropy Integration of Ozone Observations and Model Predictions: A National Application. AB - To improve ozone exposure estimates for ambient concentrations at a national scale, we introduce our novel Regionalized Air Quality Model Performance (RAMP) approach to integrate chemical transport model (CTM) predictions with the available ozone observations using the Bayesian Maximum Entropy (BME) framework. The framework models the nonlinear and nonhomoscedastic relation between air pollution observations and CTM predictions and for the first time accounts for variability in CTM model performance. A validation analysis using only noncollocated data outside of a validation radius rv was performed and the R(2) between observations and re-estimated values for two daily metrics, the daily maximum 8-h average (DM8A) and the daily 24-h average (D24A) ozone concentrations, were obtained with the OBS scenario using ozone observations only in contrast with the RAMP and a Constant Air Quality Model Performance (CAMP) scenarios. We show that, by accounting for the spatial and temporal variability in model performance, our novel RAMP approach is able to extract more information in terms of R(2) increase percentage, with over 12 times for the DM8A and over 3.5 times for the D24A ozone concentrations, from CTM predictions than the CAMP approach assuming that model performance does not change across space and time. PMID- 26998938 TI - Economic cycles and child mortality: A cross-national study of the least developed countries. AB - This paper examines the effects of growth and recession periods on child mortality in the Least Developed Countries (LDCs) during the period 1990-2010. We provide empirical evidence of uneven effects of variations in Gross Domestic Product (GDP) per capita on the evolution of child mortality rate in periods of economic recession and expansion. A decrease in GDP per capita entails a significant rise in child mortality rates, whereas an increase does not affect child mortality significantly. In this context, official development assistance seems to play a crucial role in counteracting the increment in child mortality rates in recession periods, at least in those LDCs receiving greater aid. PMID- 26998939 TI - Resilience research in schizophrenia: a review of recent developments. AB - PURPOSE OF REVIEW: The concept of resilience is expected to be relevant in understanding the heterogeneous outcomes associated with schizophrenia. We reviewed recent developments in clinical studies focusing on the biological and psychological aspects of resilience in this population. We aimed to clarify current concepts of resilience in the field, elucidate gaps in the literature, and provide recommendations for future research. RECENT FINDINGS: A total of 20 articles published between 2014 and 2015 were included. Six studies were neuroimaging studies, while the remaining studies used various psychological assessments. Most studies were cross-sectional except for three studies with naturalistic follow-up, one single-blind randomized controlled trial, and two published protocols of prospective studies. The following patterns of research were evident among the highly heterogeneous literature: studies focusing on protective factors and others emphasizing dynamic processes, studies investigating 'at-risk but resilient' groups (e.g. nonpsychotic siblings of patients with schizophrenia), and studies using psychological scales to measure resilience. SUMMARY: The heterogeneity in how reports conceptualize, assess, and interpret resilience likely reflects the multidimensional nature of the concept itself and the lack of a 'gold standard' in assessing resilience in schizophrenia. Further research is needed to make recommendations on how to facilitate resilience in clinical care. PMID- 26998940 TI - How precise is precision medicine for schizophrenia? PMID- 26998941 TI - Involvement of ethylene in gibberellic acid-induced sulfur assimilation, photosynthetic responses, and alleviation of cadmium stress in mustard. AB - The role of gibberellic acid (GA) or sulfur (S) in stimulation of photosynthesis is known. However, information on the involvement of ethylene in GA-induced photosynthetic responses and cadmium (Cd) tolerance is lacking. This work shows that ethylene is involved in S-assimilation, photosynthetic responses and alleviation of Cd stress by GA in mustard (Brassica juncea L.). Plants grown with 200 mg Cd kg(-1) soil were less responsive to ethylene despite high ethylene evolution and showed photosynthetic inhibition. Plants receiving 10 MUM GA spraying plus 100 mg S kg(-1) soil supplementation exhibited increased S assimilation and photosynthetic responses under Cd stress. Application of GA plus S decreased oxidative stress of plants grown with Cd and limited stress ethylene formation to the range suitable for promoting sulfur use efficiency (SUE), glutathione (GSH) production and photosynthesis. The role of ethylene in GA induced S-assimilation and reversal of photosynthetic inhibition by Cd was substantiated by inhibiting ethylene biosynthesis with the use of aminoethoxyvinylglycine (AVG). The suppression of S-assimilation and photosynthetic responses by inhibiting ethylene in GA plus S treated plants under Cd stress indicated the involvement of ethylene in GA-induced S-assimilation and Cd stress alleviation. The outcome of the study is important to unravel the interaction between GA and ethylene and their role in Cd tolerance in plants. PMID- 26998942 TI - A carnivorous sundew plant prefers protein over chitin as a source of nitrogen from its traps. AB - Carnivorous plants have evolved in nutrient-poor wetland habitats. They capture arthropod prey, which is an additional source of plant growth limiting nutrients. One of them is nitrogen, which occurs in the form of chitin and proteins in prey carcasses. In this study, the nutritional value of chitin and protein and their digestion traits in the carnivorous sundew Drosera capensis L. were estimated using stable nitrogen isotope abundance. Plants fed on chitin derived 49% of the leaf nitrogen from chitin, while those fed on the protein bovine serum albumin (BSA) derived 70% of its leaf nitrogen from this. Moreover, leaf nitrogen content doubled in protein-fed in comparison to chitin-fed plants indicating that the proteins were digested more effectively in comparison to chitin and resulted in significantly higher chlorophyll contents. The surplus chlorophyll and absorbed nitrogen from the protein digestion were incorporated into photosynthetic proteins - the light harvesting antennae of photosystem II. The incorporation of insect nitrogen into the plant photosynthetic apparatus may explain the increased rate of photosynthesis and plant growth after feeding. This general response in many genera of carnivorous plants has been reported in many previous studies. PMID- 26998943 TI - Isolation, spectroscopic characterization, X-ray, theoretical studies as well as in vitro cytotoxicity of Samarcandin. AB - Samarcandin 1, a natural sesquiterpene-coumarin, was isolated as well as elucidated from F. assa-foetida which has significant effect in Iranian traditional medicine because of its medicinal attitudes. The crystal structure of samarcandin was determined by single-crystal X-ray structure analysis. It is orthorhombic, with unit cell parameters a=10.8204 (5)A, b=12.9894 (7)A, c=15.2467 (9)A, V=2142.9 (2)A(3), space group P212121 and four symmetry equivalent molecules in the unit cell. Samarcandin was isolated in order to study for its theoretical studies as well as its cellular toxicity as anti-cancer drug against two cancerous cells. In comparison with controls, our microscopic and MTT assay data showed that samarcandin suppresses cancer cell proliferation in a dose dependent manner with IC50=11MUM and 13 for AGS and WEHI-164 cell lines, respectively. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) of the structure was computed by three functional methods and 6-311++G(**) standard basis set. The optimized molecular geometry and theoretical analysis agree closely to that obtained from the single crystal X-ray crystallography. To sum up, the good correlations between experimental and theoretical studies by UV, NMR, and IR spectra were found. PMID- 26998944 TI - Reassessing policy paradigms: A comparison of the global tobacco and alcohol industries. AB - Tobacco is widely considered to be a uniquely harmful product for human health. Since the mid-1990s, the strategies of transnational tobacco corporations to undermine effective tobacco control policy has been extensively documented through internal industry documents. Consequently, the sale, use and marketing of tobacco products are subject to extensive regulation and formal measures to exclude the industry from policy-making have been adopted in the Framework Convention on Tobacco Control. In contrast to tobacco, alcohol is subject to less stringent forms of regulation, and the alcohol industry continues to play a central role in policy-making in many countries and at the global level. This article examines whether there is a sufficient rationale for such different regulatory approaches, through a comparative analysis of the political economy of the tobacco and alcohol industries including the structure of the industries, and the market and political strategies they pursue. Despite some important differences, the extensive similarities which exist between the tobacco and alcohol industries in terms of market structure and strategy, and political strategy, call into question the rationale for both the relatively weak regulatory approach taken towards alcohol, and the continued participation of alcohol corporations in policy-making processes. PMID- 26998945 TI - Mental Health Disparities Among Transgender Youth: Rethinking the Role of Professionals. PMID- 26998946 TI - Eating quality prediction of beef from Italian Simmental cattle based on experts' steak assessment. AB - The experiment aimed at defining a grading scheme for Italian Simmental (IS) beef linked to objective measure of eating quality. Four experts developed a meat quality grid based on the assessment of the steak between the 8th and 9th ribs (reference steak). The grid was tested on the reference steak of 29 IS young bulls. Rib-eye dimension, meat colour, marbling, meat firmness and fat cover highly contributed to overall quality. Two classes of IS beef quality were identified: standard and high. The results were associated with the sensory profile of Longissimus thoracis muscle from the reference steaks performed by a trained panel. The differences in quality highlighted by experts in raw steak accounted for most of the relevant information regarding the sensory properties of cooked beef. The accuracy of predictive model was 96.6%. The developed scheme is a helpful tool for valuing the eating quality of beef. PMID- 26998947 TI - Relevance of nanocomposite packaging on the stability of vacuum-packed dry cured ham. AB - In this study effects of a novel high barrier multilayer polyamide film containing dispersed nanoclays (PAN) on the stability of vacuum packed dry-cured ham were investigated during 90days refrigerated storage in comparison with non modified multilayer polyamide (PA) and a commercial high barrier film. Characteristic bands of the mineral in FT-IR spectra confirmed the presence of nanoclays in PAN, enhancing oxygen transmission barrier properties and UV protection. Packaging in PAN films did not originate significant changes on colour or lipid oxidation during prolonged storage of vacuum-packed dry-cured ham. Larger oxygen transmission rates in PA films caused changes in CIE b* during refrigerated storage. Ham quality was not affected by light exposition during 90days and only curing had a significant benefit on colour and TBARS, being cured samples more stable during storage in all the packages used. Packaging of dry cured ham in PAN was equivalent to commercial high barrier films. PMID- 26998949 TI - Cost-effectiveness of individualized nutrition and exercise therapy for rehabilitation following hip fracture. AB - OBJECTIVE: To undertake a cost-utility analysis of the Individual Nutrition Therapy and Exercise Regime: A Controlled Trial of Injured, Vulnerable Elderly (INTERACTIVE) trial. DESIGN: Cost-utility analysis of a randomized controlled trial. SUBJECTS: A total of 175 patients following a hip fracture were allocated to receive either alternate weekly visits from a physical therapist and dietitian (intervention group), or social visits for 6 months (control group). METHODS: Costs for utilization of hospitals, health and community services were compared with quality-adjusted life years gained, calculated from responses to the Assessment of Quality of Life instrument. RESULTS: There were minimal differences in mean costs between the intervention ($AUD 45,331 standard deviation (SD): $AUD 23,012) and the control group ($AUD 44,764 SD: $AUD 20,712, p = 0.868), but a slightly higher mean gain in quality-adjusted life years in the intervention group (0.155, SD: 0.132) compared with the control group (0.139, SD: 0.149, p = 0.470). The incremental cost-effectiveness ratio was $AUD 28,350 per quality adjusted life year gained, which is below the implied cost-effectiveness threshold utilized by regulatory authorities in Australia. CONCLUSION: A comprehensive 6-month programme of therapy from dietitians and physical therapists could be provided at a relatively low additional cost in this group of frail older adults, and the incremental cost-effectiveness ratio indicates likely cost-effectiveness, although there was a very high level of uncertainty in the findings. PMID- 26998948 TI - Imaging Parameters and Recurrent Cerebrovascular Events in Patients With Minor Stroke or Transient Ischemic Attack. AB - IMPORTANCE: Neurological worsening and recurrent stroke contribute substantially to morbidity associated with transient ischemic attacks and strokes (TIA-S). OBJECTIVE: To determine predictors of early recurrent cerebrovascular events (RCVEs) among patients with TIA-S and National Institutes of Health Stroke Scale scores of 0 to 3. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 2 tertiary care centers (Columbia University Medical Center, New York, New York, and Tulane University Medical Center, New Orleans, Louisiana) between January 1, 2010, and December 31, 2014. All patients with neurologist diagnosed TIA-S with a National Institutes of Health Stroke Scale score of 0 to 3 who presented to the emergency department were included. MAIN OUTCOMES AND MEASURES: The primary outcome (adjudicated by 3 vascular neurologists) was RCVE: neurological deterioration in the absence of a medical explanation or recurrent TIA-S during hospitalization. RESULTS: Of the 1258 total patients, 1187 had no RCVEs and 71 had RCVEs; of this group, 750 patients (63.2%) and 39 patients (54.9%), respectively, were aged 60 years or older. There were 505 patients with TIA-S at Columbia University; 31 (6.1%) had RCVEs (15 patients had neurological deterioration only, 11 had recurrent TIA-S only, and 5 had both). The validation cohort at Tulane University consisted of 753 patients; 40 (5.3%) had RCVEs (24 patients had neurological deterioration only and 16 had both). Predictors of RCVE in multivariate models in both cohorts were infarct on neuroimaging (computed tomographic scan or diffusion-weighted imaging sequences on magnetic resonance imaging) (Columbia University: not applicable and Tulane University: odds ratio, 1.75; 95% CI, 0.82-3.74; P = .15) and large-vessel disease etiology (Columbia University: odds ratio, 6.69; 95% CI, 3.10-14.50 and Tulane University: odds ratio, 8.13; 95% CI, 3.86-17.12; P < .001). There was an increase in the percentage of patients with RCVEs when both predictors were present. When neither predictor was present, the rate of RCVE was extremely low (up to 2%). Patients with RCVEs were less likely to be discharged home in both cohorts. CONCLUSIONS AND RELEVANCE: In patients with minor stroke, vessel imaging and perhaps neuroimaging parameters, but not clinical scores, were associated with RCVEs in 2 independent data sets. Prospective studies are needed to validate these predictors. PMID- 26998953 TI - Radiology Resident Remediation: Five Important Questions to Ask. AB - OBJECTIVE: Residents needing remediation are difficult to recognize, assess, and address. The purposes of this article are to review common signs that a resident needs remediation and the causes of the deficiencies and to detail a checklist for preparing to approach the resident. CONCLUSION: Radiology residents who need remediation generally have either academic or professionalism deficits, and their remediation programs should be tailored to the deficit. Having a clear definition of the problem while eliciting the resident's thoughts on the nature of and solution to the problem are instrumental in the solution. PMID- 26998954 TI - Pharmacokinetics and pharmacodynamics of intravenous ilaprazole in healthy subjects after single ascending doses. AB - 1. Ilaprazole is a novel proton pump inhibitor and this is the first study to investigate the pharmacokinetics, pharmacodynamics and safety of intravenous ilaprazole in healthy volunteers. 2. In this open-label, single-dose, randomized and four-period crossover study, 16 healthy Chinese subjects received ilaprazole 5, 10 or 20 mg intravenously, or 10 mg orally. Serial blood and urine samples were collected and intragastric pH was recorded within 24 h. The percentage time of intragastric pH > 6 was the major index. Safety was assessed throughout the study. 3. Plasma exposure of intravenous ilaprazole increased proportionally over the dose of 5-20 mg. Clearance and volume of distribution were independent of dose. Ilaprazole was not eliminated through urine and the absolute bioavailability was 55.2%. For the intravenous dose of 5, 10, 20 mg, and oral dose of 10 mg, the mean percentages time of intragastric pH > 6 were 47.3%, 52.8%, 68.2% and 47.5%, respectively. 4. Ilaprazole showed linear pharmacokinetics over the dose of 5-20 mg. Intravenous ilaprazole provided rapid onset of action and the potency of effect were exhibited in a dose-dependent manner. Intravenous ilaprazole was safe and well tolerated except for elevated activated partial thromboplastin time (APTT) and prothrombin time (PT). PMID- 26998955 TI - Special considerations for the use of lung transplantation in pediatrics. AB - Lung transplantation has become an accepted therapy in infants, children and adolescents suffering from end-stage lung diseases, an impaired quality of life as well as a reduced life expectancy. Within Europe, pediatric lung transplantation is largely performed in predominantly adult centers due to a relatively low overall case volume. Children do represent a specific and challenging cohort facing a transplant procedure, where the selection of potential candidates becomes a crucial step to maximize net survival benefit. Therefore, interdisciplinary evaluation and early listing in view of current indications and contraindications, adequate preoperative education of the child and family members, discussion of possibly required bridging procedures in case of deterioration, appropriate technical planning of the operation, adherence to postoperative medical treatment and follow-up are all crucial steps in this demanding puzzle. In this article, the authors review recent advances in the field of pediatric lung transplantation and outline challenges in the future. PMID- 26998956 TI - Heart block following transcatheter aortic valve implantation: a matter of right bundle branch integrity? PMID- 26998957 TI - Study on dynamic characteristics' change of hippocampal neuron reduced models caused by the Alzheimer's disease. AB - In the paper, based on the electrophysiological experimental data, the Hippocampal neuron reduced model under the pathology condition of Alzheimer's disease (AD) has been built by modifying parameters' values. The reduced neuron model's dynamic characteristics under effect of AD are comparatively studied. Under direct current stimulation, compared with the normal neuron model, the AD neuron model's dynamic characteristics have obviously been changed. The neuron model under the AD condition undergoes supercritical Andronov-Hopf bifurcation from the rest state to the continuous discharge state. It is different from the neuron model under the normal condition, which undergoes saddle-node bifurcation. So, the neuron model changes into a resonator with monostable state from an integrator with bistable state under AD's action. The research reveals the neuron model's dynamic characteristics' changing under effect of AD, and provides some theoretic basis for AD research by neurodynamics theory. PMID- 26998958 TI - Missed opportunities?: an evaluation of potentially preventable poisoning deaths. AB - INTRODUCTION: Although most poisoning deaths are not preventable with current medical technology, in some cases different management decisions may have prevented fatal outcomes. OBJECTIVE: This study aims to review reported poisoning related deaths for preventability to provide insight to improve future care. METHODS: Fatality abstracts published in the US National Poison Data System (NPDS) Annual Reports (2008-2012) were analyzed. Preventability was graded using a Likert scale of 1 (definitely non-preventable) to 6 (definitely preventable). Two medical toxicologists screened all cases. Cases deemed definitely not preventable (score 1) by both reviewers were excluded from further review and considered to be "non-preventable". All cases considered at least possibly preventable by either screener were reviewed by a multidisciplinary panel of 5 physicians for preventability scoring. Differences were resolved by consensus. Cases determined to be "preventable" (scores 4-6) were characterized by type of improvement issue involved (diagnosis, treatment, monitoring, other) and recurring scenarios. RESULTS: Of 390 published abstracts, 78 (20.0%) deaths were considered at least possibly preventable by at least one screener. Of these, 34 (8.7%) deaths were determined to be "preventable" by the panel. Inter-observer agreement by weighted kappa analysis was 0.58 for screening, 0.24 for preventability, and 0.44 for specific aspects of care. The most common toxicants were salicylates (n = 9), opioids (n = 4), toxic alcohols (n = 3), fluoride containing product (n = 3), and bupropion (n = 3). The most common improvement opportunities involved treatment and monitoring. DISCUSSION: Most of the ingested substances in preventable deaths have delayed GI absorption or require metabolic activation to produce a delayed effect (such as salicylates, opioids, and toxic alcohols), and therefore provide an opportunity for early recognition and successful interventions. Most improvement opportunities are clearly described in the literature but may be not recognized. CONCLUSIONS: Based on an analysis of published NPDS data, a considerable number of poisoning-related deaths reaching medical attention may be preventable. The most common scenarios involved in potentially preventable poisoning fatalities related to monitoring and treatment. Salicylates and opioids were the most common agents involved in preventable deaths. PMID- 26998950 TI - Sodium glucose cotransporter SGLT1 as a therapeutic target in diabetes mellitus. AB - INTRODUCTION: Glycemic control is important in diabetes mellitus to minimize the progression of the disease and the risk of potentially devastating complications. Inhibition of the sodium-glucose cotransporter SGLT2 induces glucosuria and has been established as a new anti-hyperglycemic strategy. SGLT1 plays a distinct and complementing role to SGLT2 in glucose homeostasis and, therefore, SGLT1 inhibition may also have therapeutic potential. AREAS COVERED: This review focuses on the physiology of SGLT1 in the small intestine and kidney and its pathophysiological role in diabetes. The therapeutic potential of SGLT1 inhibition, alone as well as in combination with SGLT2 inhibition, for anti hyperglycemic therapy are discussed. Additionally, this review considers the effects on other SGLT1-expressing organs like the heart. EXPERT OPINION: SGLT1 inhibition improves glucose homeostasis by reducing dietary glucose absorption in the intestine and by increasing the release of gastrointestinal incretins like glucagon-like peptide-1. SGLT1 inhibition has a small glucosuric effect in the normal kidney and this effect is increased in diabetes and during inhibition of SGLT2, which deliver more glucose to SGLT1 in late proximal tubule. In short-term studies, inhibition of SGLT1 and combined SGLT1/SGLT2 inhibition appeared to be safe. More data is needed on long-term safety and cardiovascular consequences of SGLT1 inhibition. PMID- 26998959 TI - A Minimally Invasive Method in Diagnosing Testicular Torsion: The Initial Experience of Scrotoscope. AB - PURPOSE: To introduce scrotoscopy in the diagnosis of testicular torsion and evaluate its value in clinical application. PATIENTS AND METHODS: From February 2010 to June 2013, 14 patients, aged 12 to 24 years, were included into this study due to acute onset of scrotal pain. On Doppler ultrasound imaging, the blood flow decreased in seven cases (including two "no flow" cases) and remained normal in the other seven. Following anesthesia, a 10F pediatric cystoscope employed as scrotoscope was inserted into the cavity of tunica vaginalis of the testis with continued saline washing to exam the testis and epididymis. RESULTS: The scrotoscope had a diagnostic accuracy of 100% (100% specificity and 100% sensitivity), and the color Doppler ultrasound had 77.8% specificity. Five cases were diagnosed with testicular torsion, among which four were corrected and one underwent orchiectomy. No complications were observed in these patients. Nine patients with epididymitis were given oral antibiotics, and the blood flow of the testis was normal in the testis-preserving patient. CONCLUSIONS: Our study showed that scrotoscopy could serve as a minimally invasive, safe, and effective approach in the early diagnosis of testicular torsion. PMID- 26998960 TI - Successful therapy with Ledipasvir/Sofosbuvir for hepatitis C reactivation in a hematopoietic stem cell transplant recipient. PMID- 26998962 TI - The mechanism of enantioselective ketone reduction with Noyori and Noyori-Ikariya bifunctional catalysts. AB - The catalytic hydrogenation of prochiral ketones with second and third-row transition metal complexes bearing chelating chiral ligands containing at least one N-H functionality has achieved unparalleled performance, delivering, in the best cases, chiral alcohols with up to 99.9% ee using extremely small catalyst loadings (~10(-5) mol%). Hence the efficacy of this reaction has closely approached that of natural enzymatic systems and the reaction itself has become one of the most efficient artificial catalytic reactions developed to date. This article describes the current level of understanding of the mechanism of enantioselective hydrogenation and transfer hydrogenation of aromatic ketones with pioneering prototypes of bifunctional catalysts, the Noyori and Noyori Ikariya complexes. Analysis presented herein expands the concept of "metal-ligand cooperation", redefines the term "cooperative ligand" and introduces "H(-)/H(+) outer-sphere hydrogenation" as a novel paradigm in outer-sphere hydrogenation. PMID- 26998961 TI - Effectiveness of Interventions to Teach Metered-Dose and Diskus Inhaler Techniques. A Randomized Trial. AB - RATIONALE: The most effective approach to teaching respiratory inhaler technique is unknown. OBJECTIVES: To evaluate the relative effects of two different educational strategies (teach-to-goal instruction vs. brief verbal instruction) in adults hospitalized with asthma or chronic obstructive pulmonary disease. METHODS: We conducted a randomized clinical trial at two urban academic hospitals. Participants received teach-to-goal or brief instruction in the hospital and were followed for 90 days after discharge. Inhaler technique was assessed using standardized checklists; misuse was defined as 75% steps or less correct (<=9 of 12 steps). The primary outcome was metered-dose inhaler misuse 30 days postdischarge. Secondary outcomes included Diskus technique; acute care events at 30 and 90 days; and associations with adherence, health literacy, site, and patient risk (near-fatal event). MEASUREMENTS AND MAIN RESULTS: Of 120 participants, 73% were female and 90% were African American. Before education, metered-dose inhaler misuse was similarly common in the teach-to-goal and brief intervention groups (92% vs. 84%, respectively; P = 0.2). Metered-dose inhaler misuse was not significantly less common in the teach-to-goal group than in the brief instruction group at 30 days (54% vs. 70%, respectively; P = 0.11), but it was immediately after education (11% vs. 60%, respectively; P < 0.001) and at 90 days (48% vs. 76%, respectively; P = 0.003). Similar results were found with the Diskus device. Participants did not differ across education groups with regard to rescue metered-dose inhaler use or Diskus device adherence at 30 or 90 days. Acute care events were less common among teach-to-goal participants than brief intervention participants at 30 days (17% vs. 36%, respectively; P = 0.02), but not at 90 days (34% vs. 38%, respectively; P = 0.6). Participants with low health literacy receiving teach-to-goal instruction were less likely than brief instruction participants to report acute care events within 30 days (15% vs. 70%, respectively; P = 0.008). No differences existed by site or patient risk at 30 or 90 days (P > 0.05). CONCLUSIONS: In adults hospitalized with asthma or chronic obstructive pulmonary disease, in-hospital teach-to-goal instruction in inhaler technique did not reduce inhaler misuse at 30 days, but it was associated with fewer acute care events within 30 days after discharge. Inpatient treatment-to goal education may be an important first step toward improving self-management and health outcomes for hospitalized patients with asthma or chronic obstructive pulmonary disease, especially among patients with lower levels of health literacy. Clinical trial registered with www.clinicaltrials.gov (NCT01426581). PMID- 26998963 TI - Isolation and Synthesis of a Bacterially Produced Inhibitor of Rosette Development in Choanoflagellates. AB - The choanoflagellate Salpingoeca rosetta is a microbial marine eukaryote that can switch between unicellular and multicellular states. As one of the closest living relatives of animals, this organism has become a model for understanding how multicellularity evolved in the animal lineage. Previously our laboratories isolated and synthesized a bacterially produced sulfonolipid that induces S. rosetta to form multicellular "rosettes." In this study, we report the identification of a bacterially produced inhibitor of rosettes (IOR-1) as well as the total synthesis of this molecule and all of its stereoisomers. Our results confirm the previously noted specificity and potency of rosette-modulating molecules, expand our understanding of the complex chemical ecology between choanoflagellates and rosette-inducing bacteria, and provide a synthetic probe template for conducting further mechanistic studies on the emergence of multicellularity. PMID- 26998965 TI - Size-Dependence of Acceptor and Donor Levels of Boron and Phosphorus Codoped Colloidal Silicon Nanocrystals. AB - Size dependence of the boron (B) acceptor and phosphorus (P) donor levels of silicon (Si) nanocrystals (NCs) measured from the vacuum level was obtained in a very wide size range from 1 to 9 nm in diameter by photoemission yield spectroscopy and photoluminescence spectroscopy for B and P codoped Si-NCs. In relatively large Si-NCs, both levels are within the bulk Si band gap. The levels exhibited much smaller size dependence compared to the valence band and conduction band edges. The Fermi level of B and P codoped Si-NCs was also studied. It was found that the Fermi level of relatively large codoped Si-NCs is close to the valence band and it approaches the middle of the band gap with decreasing the size. The results suggest that below a certain size perfectly compensated Si-NCs, that is, Si-NCs with exactly the same number of active B and P, are preferentially grown, irrespective of average B and P concentrations in samples. PMID- 26998964 TI - Block Copolymer-Encapsulated CaWO4 Nanoparticles: Synthesis, Formulation, and Characterization. AB - We envision that CaWO4 (CWO) nanocrystals have the potential for use in biomedical imaging and therapy because of the unique ways this material interacts with high-energy radiation. These applications, however, require development of nanoparticle (NP) formulations that are suitable for in vivo applications; primarily, the formulated nanoparticles should be sufficiently small, chemically and biologically inert, and stable against aggregation under physiological conditions. The present study demonstrates one such method of formulation, in which CWO nanoparticles are encapsulated in bioinert block copolymer (BCP) micelles. For this demonstration, we prepared three different CWO nanocrystal samples having different sizes (3, 10, and 70 nm in diameter) and shapes (elongated vs truncated rhombic). Depending on the specific synthesis method used, the as-synthesized CWO NPs contain different surfactant materials (citric acid or cetyltrimethylammonium bromide or a mixture of oleic acid and oleylamine) in the coating layers. Regardless of the type of surfactant, the original surfactant coating can be replaced with a new enclosure formed by BCP materials using a solvent-exchange method. Two types of BCPs have been tested: poly(ethylene glycol-block-n-butyl acrylate) (PEG-PnBA) and poly(ethylene glycol block-D,L-lactic acid) (PEG-PLA). Both BCPs are able to produce fully PEGylated CWO NPs that are stable against aggregation under physiological salt conditions for very long periods of time (at least three months). The optical and radio luminescence properties of both BCP-encapsulated and surfactant-coated CWO NPs were extensively characterized. The study confirms that the BCP coating structure does not influence the luminescence properties of CWO NPs. PMID- 26998966 TI - An Innovative Collagen-Based Cell-Printing Method for Obtaining Human Adipose Stem Cell-Laden Structures Consisting of Core-Sheath Structures for Tissue Engineering. AB - Three-dimensional (3D) cell printing processes have been used widely in various tissue engineering applications due to the efficient embedding of living cells in appropriately designed micro- or macro-structures. However, there are several issues to overcome, such as the limited choice of bioinks and tailor-made fabricating strategies. Here, we suggest a new, innovative cell-printing process, supplemented with a core-sheath nozzle and an aerosol cross-linking method, to obtain multilayered cell-laden mesh structure and a newly considered collagen based cell-laden bioink. To obtain a mechanically and biologically enhanced cell laden structure, we used collagen-bioink in the core region, and also used pure alginate in the sheath region to protect the cells in the collagen during the printing and cross-linking process and support the 3D cell-laden mesh structure. To achieve the most appropriate conditions for fabricating cell-embedded cylindrical core-sheath struts, various processing conditions, including weight fractions of the cross-linking agent and pneumatic pressure in the core region, were tested. The fabricated 3D MG63-laden mesh structure showed significantly higher cell viability (92 +/- 3%) compared with that (83 +/- 4%) of the control, obtained using a general alginate-based cell-printing process. To expand the feasibility to stem cell-embedded structures, we fabricated a cell-laden mesh structure consisting of core (cell-laden collagen)/sheath (pure alginate) using human adipose stem cells (hASCs). Using the selected processing conditions, we could achieve a stable 3D hASC-laden mesh structure. The fabricated cell-laden 3D core-sheath structure exhibited outstanding cell viability (91%) compared to that (83%) of an alginate-based hASC-laden mesh structure (control), and more efficient hepatogenic differentiations (albumin: ~ 1.7-fold, TDO-2: ~ 7.6-fold) were observed versus the control. The selection of collagen-bioink and the new printing strategy could lead to an efficient way to achieve 3D cell-laden mesh structures that mimic the anatomical architecture of a patient's defective region. PMID- 26998969 TI - Elevated Levels of Total Cell-Free DNA in Maternal Serum Samples Arise from the Generation of Neutrophil Extracellular Traps. AB - INTRODUCTION: The analysis of cell-free DNA from maternal blood samples has facilitated the noninvasive detection of fetal aneuploidies or hereditary Mendelian disorders. In this context, previous studies have indicated that the pool of cell-free DNA is greater in maternal serum than in plasma samples, necessitating optimized collection and storage protocols. As the source of this increased amount of cell-free DNA is not clear, we have now examined whether neutrophil extracellular traps (NETs) contribute to this material. MATERIAL AND METHODS: Serum samples were collected in all three trimesters of normal healthy pregnant women, and at term from cases with manifest preeclampsia. The presence of NET-derived material was demonstrated by the detection of cell-free DNA fragments complexed to neutrophil granular proteins (i.e. myeloperoxidase). RESULTS: Our data indicate that NET-derived cell-free DNA/myeloperoxidase complexes were greater in serum from normal pregnant women than in normal matching nonpregnant controls. This neutrophil chromosomal material increased incrementally throughout gestation and was most pronounced in cases with preeclampsia. DISCUSSION: By detecting increased levels of cell-free DNA/myeloperoxidase complexes in maternal serum samples, our data indicate that a significant proportion of this material is derived from the generation of NETs. PMID- 26998968 TI - Factors Associated with the Combined Use of Antidepressants and Benzodiazepines in Major Depression: A Case-Control Study. AB - The aim of this study was to identify the factors associated with the combined use of antidepressants and benzodiazepines (BDZs) in patients with major depression. We conducted a case-control study in the public health service of the city of Sao Paulo, Brazil. The participants were all patients being treated with antidepressants, who were diagnosed with major depression. Patients who received a combination of antidepressants and BDZs were classified as cases, and those who used only antidepressants, as controls. Data were obtained from a pharmacy database, medical records and interviews with the healthcare team. The association of predisposing factors for combined therapy was analysed using logistic regression analysis, and the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of the 1355 users of antidepressants, 265 had major depression, of whom 138 were cases and 127 were controls. The factors associated with combined use were age older than 35 years (OR 2.2, 95% CI 1.0 4.7), absence of comorbidities (OR 2.3, 95% CI 1.4-4.1) and no use of other drugs (OR 1.9, 95% CI 1.1-3.3). Patients with combined use were more likely to exhibit inadequate prescribing, including inappropriate antidepressants (OR 4.7, 95% CI 2.2-9.9), inadequate dosages (OR 3.62, 95% CI 1.4-9.6) and/or a non-recommended duration (OR 66.6, 95% CI 18.4-240.7). The factors identified showed the groups most susceptible to combined use in this population, who in turn are more likely to receive inappropriate prescriptions. PMID- 26998967 TI - Early impact of the Patient Protection and Affordable Care Act on insurance among young adults with cancer: Analysis of the dependent insurance provision. AB - BACKGROUND: The Patient Protection and Affordable Care Act (ACA) included provisions to extend dependent health care coverage up to the age of 26 years in 2010. The authors examined the early impact of the ACA (before the implementation of insurance exchanges in 2014) on insurance rates in young adults with cancer, a historically underinsured group. METHODS: Using National Cancer Institute Surveillance, Epidemiology, and End Results data for 18 cancer registries, the authors examined insurance rates before (pre) (January 2007-September 2010) versus after (post) (October 2010-December 2012) dependent insurance provisions among young adults aged 18 to 29 years when diagnosed with cancer during 2007 through 2012. Using multivariate generalized mixed effect models, the authors conducted difference-in-differences analysis to examine changes in overall and Medicaid insurance after the ACA among young adults who were eligible (those aged 18-25 years) and ineligible (those aged 26-29 years) for policy changes. RESULTS: Among 39,632 young adult cancer survivors, the authors found an increase in overall insurance rates in those aged 18 to 25 years after the dependent provisions (83.5% for pre-ACA vs 85.4% for post-ACA; P<.01), but not among individuals aged 26 to 29 years (83.4% for pre-ACA vs 82.9% for post-ACA; P = .38). After adjusting for patient sociodemographics and cancer characteristics, the authors found that those aged 18 to 25 years had a 3.1% increase in being insured compared with individuals aged 26 to 29 years (P<.01); however, there were no significant changes noted in Medicaid enrollment (P = .17). CONCLUSIONS: The findings of the current study identify an increase in insurance rates for young adults aged 18 to 25 years compared with those aged 26 to 29 years (1.9% vs -0.5%) that was not due to increases in Medicaid enrollment, thereby demonstrating a positive impact of the ACA dependent care provisions on insurance rates in this population. Cancer 2016;122:1766-73. (c) 2016 American Cancer Society. PMID- 26998970 TI - Mining Social Entrepreneurship Strategies Using Topic Modeling. AB - Despite the burgeoning research on social entrepreneurship (SE), SE strategies remain poorly understood. Drawing on extant research on the social activism and social change, empowerment and SE models, we explore, classify and validate the strategies used by 2,334 social entrepreneurs affiliated with the world's largest SE support organization, Ashoka. The results of the topic modeling of the social entrepreneurs' strategy profiles reveal that they employed a total of 39 change making strategies that vary across resources (material versus symbolic strategies), specificity (general versus specific strategies), and mode of participation (mass versus elite participation strategies); they also vary across fields of practice and time. Finally, we identify six meta-SE strategies-a reduction from the 39 strategies-and identify four new meta-SE strategies (i.e., system reform, physical capital development, evidence-based practices, and prototyping) that have been overlooked in prior SE research. Our findings extend and deepen the research into SE strategies and offer a comprehensive model of SE strategies that advances theory, practice and policy making. PMID- 26998971 TI - Couples' willingness to donate embryos for research: a longitudinal study. AB - INTRODUCTION: Decision-making on embryo disposition is a source of distress and is subject to change over time. This paper analyzes the willingness of couples undergoing in vitro fertilization to donate cryopreserved embryos for research from 15 days after embryo transfer to 12 months later, taking into account the influence of psychosocial, demographic, and reproductive factors. MATERIAL AND METHODS: Prospective longitudinal study, with 74 heterosexual couples undergoing in vitro fertilization in a public fertility centre in Portugal, recruited between 2011 and 2012. Participants were evaluated twice: 15 days after embryo transfer and 12 months later. RESULTS: A significant decrease in patients' willingness to donate embryos for research over time was observed [86.5% to 73.6%; relative risk (RR) = 0.85; 95% CI 0.76-0.95]. A higher education level (>12 years) [adjusted RR (RRadj ) = 0.79; 95% CI 0.64-0.96], considering research on human embryos to be important (vs. very important) (RRadj = 0.59; 95% CI 0.39 0.85) and practicing a religion less than once a month (vs. at least once a month) (RRadj = 0.73; 95% CI 0.53-1.00) seemed associated with unwillingness to donate embryos for research over time. Change towards non-donation happened mainly among couples who first considered that it was better to donate than wasting the embryos. Change towards donation occurred mostly among those stating that their priority at time 1 was to have a baby and who became pregnant in the meantime. CONCLUSIONS: Quality of care guided by patients' characteristics, values, preferences, and needs calls for considering the factors and reasons underlying couples' willingness to donate embryos for research over time as a topic in psychosocial guidelines for infertility and medically assisted reproductive care. PMID- 26998972 TI - Patient-Reported Experience of Modified Transperineal Template Guided Saturation Biopsy Under General Anaesthesia and without Prophylactic Catheterisation. AB - Results of patient feedback questionnaire following transperineal template guided saturation biopsy (TPSB) without prophylactic catheterisation. INTRODUCTION AND OBJECTIVE: TPSB is increasingly utilised in the diagnosis and characterisation of prostate cancer. However, there is little data on patient experience after undergoing this procedure. We circulated a questionnaire to 511 consecutive patients from July 2007 to December 2014 and now analyse the responses. MATERIALS AND METHODS: The mean age for the cohort was 64 (range 43-82). A mean of 28 biopsy cores (range 13-43) were taken under general anaesthesia (GA), as day case procedure. Patients received diclofenac 100 mg suppository on completion of the procedure. The questionnaire explored symptoms at 1 h, 1, 3 and 7 days postoperatively. RESULTS: There were 301 responses (59%). Following TPSB, 38% initially experienced rectal bleeding, falling significantly to 3% on day 7 (p < 0.001) and it was not a serious condition in all cases. A majority reported haematuria at 1 h but persisting at 1 week in over one quarter (p < 0.001). Nevertheless, although initially often dark, none had other than pale pink by the end of the reporting period. In contrast, the incidence of haematospermia increased over 7 days, rising significantly to 38% by this stage (p < 0.001). Several patients commented that the procedure was more tolerable than their previous conventional TRUS biopsy and 20 (6.6%) with voiding difficulty required catheterisation. In all, 23% patients felt pain, and out of these 23% only 5% required minor analgesia at day 7. CONCLUSION: TPSB under GA without prophylactic catheterisation is well tolerated, carrying acceptable postoperative symptom rates. Interestingly, a significant proportion of patients ejaculate within 7 days, which again suggests good tolerance to the procedure. Patients should be provided with this data preoperatively when they are considering TPSB. PMID- 26998973 TI - Cancer stem cell-still an enigma in CTCL? PMID- 26998974 TI - Reply. PMID- 26998975 TI - Role of the lens in controlling physical dormancy break and germination of Delonix regia (Fabaceae: Caesalpinioideae). AB - Physical dormancy occurs in all three subfamilies of Fabaceae, namely Mimosoideae, Papilionoideae and Caesalpinioideae, making it one of the largest plant families in terms of number of species with physical dormancy. However, little is known about the water gap structure and germination ecology of species in Caesalpinioideae. Freshly collected seeds of Delonix regia (Caesalpinioideae) did not imbibe water, thus they had physical dormancy. Both dry heat and wet heat were effective in breaking dormancy, however, longer duration was required at 80 degrees C and shorter duration at 90 degrees C. Seeds buried in the field for 2 years germinated to 21% and 42% after the first and second summer, respectively, compared with 3% germination in seeds at the time of maturity. Seeds incubated at 15/60 degrees C in the laboratory (mimicking summer conditions) for 3 months supported this conclusion, as dormancy was relieved in 18% and 24% of seeds stored dry and watered intermediately, respectively. All the dormancy breaking treatments resulted in lifting of palisade layers in the lens region to form a circular lid-like opening, i.e. water gap (Type II simple). Blocking experiments confirmed that water entered only through the lens and no secondary water entry point was observed. No apparent changes in morphology/anatomy of the hilum region were noted in dormant and non-dormant (water permeable) seeds. These results suggest that summer temperatures could open the lens in a proportion of seeds every year and that germination occurs during the subsequent wet season in the tropics. PMID- 26998976 TI - [Shortening undergraduate medical training: now and for all medical schools in Chile?]. AB - In Chile, undergraduate medical education starts after High School, it lasts seven years, with the final two dedicated to a rotary internship, taking to an M.D. degree that allows the graduate to enter working activities. The country needs more M.D.s in primary care, but there is also a shortage of specialists, mainly out of the main cities. In recent decades, post graduate programs leading to specialty titles have become competitively adopted by a large proportion of medical graduates. This is the case at the Pontificia Universidad Catolica de Chile, stimulating its faculties and medical students to develop a collaborative review of their teaching programs, leading to a curricular reform with a new graduate profile and a new curriculum oriented to learning objectives, that will allow to obtain the M.D. degree in six instead of seven years of undergraduate education. This new program awakened expectations in other universities in Chile, that will have to face the attraction of this shortened program for future candidates to enter medical schools. However, any shortening of medical school careers should first consider the local conditions in quality of applicants, number of accepted students, the training of teachers in integrated teaching programs, the availability of adequate campuses. Furthermore, for students with different academic backgrounds and diverse personal and familial interests, the seven years programs may still be necessary to gain the expertise required to become medical doctors. PMID- 26998977 TI - Sharing clinical trial data: a proposal from the International Committee of Medical Journal Editors. PMID- 26998978 TI - [Ethical issues perceived by health care professionals working in chronic hemodialysis centers]. AB - BACKGROUND: Clinical teams working at chronic hemodialysis centers (CHC) frequently have to face ethical problems, but there is no systematic approach to deal with them. AIM: To study the ethical problems perceived by health professionals at CHC. MATERIAL AND METHODS: Eighty randomly selected physicians and 139 nurses from 23 CHC, answered a structured questionnaire, devised by the research team. RESULTS: Twenty-six percent of respondents had postgraduate studies in clinical ethics. The ethical problems mentioned by respondents were therapeutic disproportion in 66.7%, lack of communication between patients, their families and the clinical team in 25.9%, personal conflicts of interests related with hemodialysis prescription in 14.6% and conflicts of interests of other members of the clinical team in 30.6%. The percentage of respondents that experienced not starting or discontinuing hemodialysis treatment due to decision of patients? relatives was 86.8%. Only 45.2% of health professionals had the opportunity to take part in decision-making meetings. Eighty seven percent of respondents supported the use of advanced directives in the event of a cardio respiratory arrest during treatment. CONCLUSIONS: To improve the approach to ethical problems in CHC, it is necessary to improve training in clinical ethics, promote an effective dialogue between the patients, their families and health professionals, and follow their advance directives in case of cardiac arrest during treatment. PMID- 26998979 TI - [Long-term outcomes with expanded criteria donors in kidney transplantation]. AB - BACKGROUND: Kidney transplantation of expanded criteria deceased donors (DCE) has become a common clinical practice. However, DCE outcomes are inferior compared to kidney transplants from standard criteria donors (DCS). AIM: To evaluate intermediate and long-term outcomes of DCE transplanted patients. MATERIAL AND METHODS: Cadaveric kidney transplants were evaluated using a retrospective cohort of eight consecutive years. Complications and long-term function of the transplant were assessed in DCE and DCS kidney recipients. RESULTS: Of 213 patients analyzed, 34 (16%) underwent DCE transplantation. DCS recipients spent more time on the waiting list for transplantation (p = 0.04). DCE recipients showed higher frequency of surgical complications (p = 0.04), vascular complications (p = 0.02), acute transplant rejection (p = 0.05), and hospitalizations (p = 0.01). Creatinine (mg/dL) in DCE and DCS recipients was 2.3 and 1.5 respectively at year one (p < 0.01) and 2.6 and 1.6 respectively at year five (p < 0.01). Graft survival in the DCE group was significantly lower at 5 years (61 and 89% respectively, p < 0.01). CONCLUSIONS: DCE grafts are associated with lower survival, higher hospitalization rate and commonly develop surgical complications and rejections. PMID- 26998980 TI - [Subclinical atherosclerosis among Chilean subjects classified as having a low cardiovascular Framingham risk]. AB - BACKGROUND: Framingham risk score (FRS) has limitations and can underestimate risk. Carotid ultrasound to measure intima media thickness or plaques is recommended for cardiovascular risk assessment. AIM: To determine the prevalence of subclinical atherosclerosis in asymptomatic subjects classified as low and intermediate risk. MATERIAL AND METHODS: Cross-sectional study performed in subjects without cardiovascular disease. Cardiovascular risk was estimated using the Chilean FRS and the General Cardiovascular Disease FRS. Carotid ultrasound was performed in all subjects. We defined subclinical atherosclerosis as the presence of carotid plaque or intima media thickness greater than 75th percentile by gender and age. RESULTS: We studied 203 subjects aged 47.2 +/- 9.6 years (54% males). Mean intima media thickness was 0.62 +/- 0.1 mm. An abnormal value was detected in 68 subjects (33%) and carotid plaques in 32 subjects (15.7%). Based on Chilean FRS, 96% were considered at low risk, 4% at intermediate, and none at high risk. In the low risk group the prevalence of abnormal intima media thickness and plaques was 40 and 14% respectively. Presence of plaques was more common in women than men (23 and 7% respectively, p < 0.01). According to the General Cardiovascular Disease FRS, 23% were at low, 39% at low intermediate and 28% at high intermediate risk. In the low risk group the prevalence of an abnormal intima media thickness was 34% and no subject had plaques. CONCLUSIONS: Carotid plaques were detected in Chilean subjects classified as having a low FRS risk. The underestimation of risk was higher in Chilean women. PMID- 26998981 TI - [Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction]. AB - BACKGROUND: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. AIM: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. MATERIAL AND METHODS: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. RESULTS: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. CONCLUSIONS: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management. PMID- 26998982 TI - [Clinical skills of Chilean general practitioners for the management of depressive disorders]. AB - BACKGROUND: Diverse and sustained efforts have been developed to improve the management of depression by general practitioners (GPs), but they have not improved treatment coverage and quality of services. AIM: To explore the level of knowledge and clinical skills to diagnose and treat depression by GPs in Primary Health Care (PHC) in the Metropolitan Area of Santiago de Chile (RM). MATERIAL AND METHODS: Theoretical knowledge (TK), diagnostic skills (DS) and treatment skills (TS) were evaluated in 56 GPs of the RM with a battery of specially designed instruments. RESULTS: In TK there were significant differences between GPs aged 31 years or less and their older counterparts and between Chilean and foreign doctors. Five percent of observed differences in TK were explained by age and nationality, respectively. Chilean GPs achieved higher scores in recognition of symptoms (RS), one of the dimensions of DS. No significant differences by age or nationality were observed for DS and TS. CONCLUSIONS: Achievement of GPs on tests measuring TK, DS, and TS was generally below 50%. This deficiency should be improved. PMID- 26998983 TI - [Evaluation of the Charing Cross Venous Ulcer Questionnaire in patients with chronic venous ulcers in Uruguay]. AB - BACKGROUND: Chronic venous ulcers (CVU) represent a frequent condition, with difficult therapeutic approaches, that impact on patients? quality of life, and generate an economic burden to patients and health systems. AIM: To perform the cultural adaptation and initial evaluation of the Charing Cross Venous Ulcer Questionnaire (CCVUQ) for Uruguay, and to study the health-related quality of life (HRQL) of patients with CVU. MATERIAL AND METHODS: The translated and culturally adapted version of the CCVUQ was applied to a convenience sample of 50 patients. In addition, the PROMIS Global Health Survey was included in the assessment. RESULTS: Both questionnaires showed good internal consistency (Cronbach alfa > 0.70). A statistically significant association was observed between the CCVUQ total scores, its subscales and both dimensions of the PROMIS: Global Physical (GPH) and Global Mental Health (GMH) (rho >= 0.40). The CCVUQ mean score was 54.9 +/- 42 points while GPH and GMH mean scores were 37.9 +/- 29 points, and 43.1 +/- 35.1 points respectively. Simple linear regression showed that patients with higher income reported better emotional well-being, while in younger patients, ulcers had a higher impact on Emotional Status and Cosmetics. CONCLUSIONS: The translated and adapted version of the CCVUQ was easy to comprehend and apply, showing good psychometric properties. When used in association with the PROMIS Global Health Measure it provides complementary information. HRQL was severely affected in the study sample. PMID- 26998984 TI - [Pre and intraoperative scintigraphic detection of sentinel nodes in breast cancer]. AB - BACKGROUND: Sentinel node detection localizes the first node that drains a malignant lesion aiming to detect tumor dissemination. AIM: To assess the yield of sentinel node detection in breast cancer, using pre or intraoperative scintigraphy. MATERIAL AND METHODS: Review of medical records of patients with breast cancer who had a scintigraphic detection of sentinel nodes. Lymph node scintigraphy and surgery were performed in the same day. RESULTS: We studied 174 women aged 53 +/- 13 years, operated with a diagnosis of breast cancer, including six highly suspicious lesions in the contralateral breast (totaling 180 studied breasts). Preoperative scintigraphy showed a sentinel node in 174 of 180 breasts (97%). Intraoperative gamma probe confirmed the presence of the sentinel node in the same 174 breasts and detected an additional one reaching a detection yield of 97%. Four patients in whom a sentinel node was not detected in the preoperative scintigraphy, had macrometastases. Frozen section biopsies were available in 177 of 180 breasts. Metastases were informed in 45 patients who underwent axillary lymph node dissection, plus one additional patient with a suspicious lesion. CONCLUSIONS: A high rate of sentinel node detection in the preoperative scintigraphy was observed. Most sentinel nodes not detected with nuclear medicine had macrometastases. In 71% of patients, the detection of sentinel node avoided axillary lymph node dissection. PMID- 26998985 TI - [Changes associated with aging in angular kinematic parameters during a controlled speed walk]. AB - BACKGROUND: During normal aging, a reduction in walking speed and changes in stability are observed. AIM: To characterize and compare gait kinematic parameters of young (YA) and older adults (OA) at a controlled speed. MATERIAL AND METHODS: Gait angular kinematic parameters were analyzed in OA aged over 60 years and YA aged between 20 and 30 years. For data capture, six VICON Bonita cameras were used. Recording were made at a gait speed of 1.2 m/s. Kinematic data were normalized to 100% of the gait cycle using the Polygon 4.1 software. Time windows representing the phases of gait were created for analysis. RESULTS: At the hip-pelvis level, OA reduce their pelvic obliquity motion and increase hip abduction. At the knee level OA reduce movements in the frontal plane during the plantar support and half swing phases. At the ankle level OA reduce their maximum ranges of plantar flexion, during the toe-off and final swing phases. CONCLUSIONS: At a controlled speed, kinematic changes observed in OA allow an increase in body support base to maintain gait stability. PMID- 26998986 TI - [Management of pediatric status epilepticus]. AB - Pediatric Status Epilepticus (SE) is an emergency situation with high morbidity and mortality that requires early and aggressive management. The minimum time criterion to define SE was reduced from 30 to 5 minutes, defined as continuous seizure activity or rapidly recurrent seizures without resumption of consciousness for more than 5 minutes. This definition considers that seizures that persist for > 5 minutes are likely to do so for more than 30 min. Those that persist for more than 30 minutes are more difficult to treat. Refractory SE is the condition that extends beyond 60-120 minutes and requires anesthetic management. Super-refractory SE is the state of no response to anesthetic management or relapse during withdrawal of these drugs. The aim of this review is to provide and update on convulsive SE concepts, pathophysiology, etiology, available antiepileptic treatment and propose a rational management scheme. A literature search of articles published between January 1993 and January 2013, focused on pediatric population was performed. The evidence about management in children is limited, mostly corresponds to case series of patients grouped by diagnosis, mainly adults. These publications show treatment alternatives such as immunotherapy, ketogenic diet, surgery and hypothermia. A 35% mortality, 26% of neurological sequelae and 35% of recovery to baseline condition is described on patient?s evolution. PMID- 26998987 TI - [Palliative care of patients with severe dementia]. AB - Dementia is an important public health problem due to the complex challenges it poses during the progression of the disease and especially during its end-of-life stage. The aim of this article is to consider the issues that arise from the use of commonly administered therapies in patients with severe dementia. Scenarios where excessive or futile therapeutic interventions might occur are discussed. The article concludes that it is advisable to analyze the clinical criteria and ethical considerations related to the administration of those treatments in order to develop and disseminate better practice guidelines for health professionals. PMID- 26998988 TI - [Curriculum reform at the Pontificia Universidad Catolica de Chile School of Medicine]. AB - The career of Medicine at the Pontificia Universidad Catolica de Chile was established from the beginning (1929), with a classical Flexner curriculum design. In seven years, the career is divided in three cycles: basic sciences, clinics and internship. It obtained Chilean accreditation and fulfilled American Association of Medical Colleges accreditation requirements. Changes in the Chilean epidemiological profile and health system, and new teaching methods in medicine, stimulated a process of deep curricular analysis, identifying strengths and weaknesses of the medical career. The curricular strengths were well developed scientific and clinical components, fully committed students and faculties, well defined learning objectives and excellent clinical campuses. Curricular weaknesses included a poor vertical and horizontal integration, few student centered methodologies and a weak emphasis concerning doctor?s professionalism. Subsequently, the whole community of teachers, students and medical educators worked on the design of a new curriculum, establishing a new graduate profile and designed it oriented by learning objectives, of six years of duration, with an optimized course sequence that melds basic science and clinical concepts, with strong emphasis on humanities and professionalism. It prioritizes an early contact with patients from the first year and expands teaching methods. The main objective of this process was to achieve a new curriculum with an integrative structure. This was implemented in 2015 with an approved protocol to evaluate the outcomes. PMID- 26998989 TI - [Minimum legal drinking age in the Chilean context]. AB - Alcohol consumption is harmful to minors. One of the most wide ly accepted measures for the prevention of harm associated with alcohol consumption for young people is to establish a minimum legal drinking age. This document presents the evidence available on this policy, offers a condensed analysis of its characteristics in the United States of America, describes current consumption patterns of Chilean youth, and proposes concrete solutions to be implemented. PMID- 26998990 TI - [Hygiene and urban health as seen by physicians, architects and planners during the first half of the twentieth century]. AB - Physicians took part in the promotion of public policies that regulated urban and architectural work, before engineers, architects, planners, and even before the State had a chance to take part in the formulation of such policies. Starting in the late nineteenth century, and especially during the first decade of the twentieth century, the State began to lead on the issue of hygiene and public health. This paper focuses on the role of these professionals, who generated debates within their respective disciplines, or provided -as ministries, public servants or consultants- technical knowledge to the central government. These debates are still relevant for two reasons. First, they serve as reminders of the way in which the voice of these professionals was crucial not only within their respective disciplines, but also in order to place the issue of hygiene and public health on the agenda and to promote public policies related to the urban environment and its population. Secondly, these debates represent a challenge to current planners, as this historic context provides insight on the complex relationship between public health and planning, which hitherto has received little attention. PMID- 26998992 TI - [Hypoglycemia induced by a solitary fibrous tumor of the lung or Doege-Potter syndrome: Report of one case]. AB - We report the case of a 75-year-old man who was admitted to the hospital with symptoms of severe hypoglycemia. He had a history of solitary fibrous tumor diagnosed by Pathology after its complete surgical resection eight years before. The laboratory examination reported hypoglycemia with inhibited Insulin secretion. A computed tomography of the thorax revealed a large solid heterogeneous mass in the left hemithorax. Solitary fibrous tumor is a rare neoplasm. The association of solitary fibrous tumor and paraneoplastic hypoglycemia is known as Doege-Potter syndrome and occurs in less than 5% of all solitary fibrous tumors. PMID- 26998991 TI - [Cerebriform variant type of T cell prolymphocytic leukemia: Report of one case]. AB - T cell Prolymphocytic Leukemia (T-PLL) is a rare and aggressive mature T cell Lymphocyte Leukemia. Twenty five percent of cases present as a small cell variant, and only 5% as a cerebriform variant. We report a 58 year-old man with rapidly progressive severe leukocytosis, skin lesions, lymphadenopathy, hepatosplenomegaly and pleural effusion. The lymphocytes had a cerebriform type. The diagnosis of T-PLL variant was made by morphology and immunophenotype study of peripheral blood. Karyotype was found to be complex. He was refractory to chemotherapy and died two months later. PMID- 26998993 TI - [Outdoor fitness equipment in parks, in Santiago, Chile]. PMID- 26998994 TI - [Active squares: Who prescribes and dispenses the exercise?]. PMID- 26998995 TI - [CORRECTION]. PMID- 26998996 TI - Restless legs syndrome in migraine patients: prevalence and severity. AB - BACKGROUND AND PURPOSE: Our aim was to study not only the prevalence but more importantly the severity and the correlation between sleep quality and restless legs syndrome (RLS) in a large population of well-defined migraine patients as poor sleep presumably triggers migraine attacks. METHODS: In a large cross sectional and observational study, data on migraine and RLS were collected from 2385 migraine patients (according to the International Classification of Headache Disorders ICHD-IIIb) and 332 non-headache controls. RLS severity (International RLS Study Group severity scale) and sleep quality (Pittsburgh Sleep Quality Index) were assessed. Risk factors for RLS and RLS severity were calculated using multivariable-adjusted regression models. RESULTS: Restless legs syndrome prevalence in migraine was higher than in controls (16.9% vs. 8.7%; multivariable adjusted odds ratio 1.83; 95% confidence interval 1.18-2.86; P = 0.008) and more severe (adjusted severity score 14.5 +/- 0.5 vs. 12.0 +/- 1.1; P = 0.036). Poor sleepers were overrepresented amongst migraineurs (50.1% vs. 25.6%; P < 0.001). Poorer sleep quality was independently associated with RLS occurrence (odds ratio 1.08; P < 0.001) and RLS severity (P < 0.001) in migraine patients. CONCLUSION: Restless legs syndrome is not only twice as prevalent but also more severe in migraine patients, and associated with decreased sleep quality. PMID- 26998997 TI - miTALOS v2: Analyzing Tissue Specific microRNA Function. AB - MicroRNAs are involved in almost all biological processes and have emerged as regulators of signaling pathways. We show that miRNA target genes and pathway genes are not uniformly expressed across human tissues. To capture tissue specific effects, we developed a novel methodology for tissue specific pathway analysis of miRNAs. We incorporated the most recent and highest quality miRNA targeting data (TargetScan and StarBase), RNA-seq based gene expression data (EBI Expression Atlas) and multiple new pathway data sources to increase the biological relevance of the predicted miRNA-pathway associations. We identified new potential roles of miR-199a-3p, miR-199b-3p and the miR-200 family in hepatocellular carcinoma, involving the regulation of metastasis through MAPK and Wnt signaling. Also, an association of miR-571 and Notch signaling in liver fibrosis was proposed. To facilitate data update and future extensions of our tool, we developed a flexible database backend using the graph database neo4j. The new backend as well as the novel methodology were included in the updated miTALOS v2, a tool that provides insights into tissue specific miRNA regulation of biological pathways. miTALOS v2 is available at http://mips.helmholtz muenchen.de/mitalos. PMID- 26998999 TI - An Updated Synthesis of the Diazo-Transfer Reagent Imidazole-1-sulfonyl Azide Hydrogen Sulfate. AB - Imidazole-1-sulfonyl azide and salts thereof are valuable reagents for diazo transfer reactions, most particularly conversion of primary amines to azides. The parent reagent and its HCl salt present stability and detonation risks, but the hydrogen sulfate salt is significantly more stable. An updated procedure for the large-scale synthesis of this salt avoids isolation or concentration of the parent compound or HCl salt and will facilitate the use of hydrogen sulfate salt as the reagent of choice for diazo transfer. PMID- 26998998 TI - Metal-specific control of gene expression mediated by Bradyrhizobium japonicum Mur and Escherichia coli Fur is determined by the cellular context. AB - Bradyrhizobium japonicum Mur and Escherichia coli Fur are manganese- and iron responsive transcriptional regulators, respectively, that belong to the same protein family. Here, we show that neither Mur nor Fur discriminate between Fe(2+) and Mn(2+) in vitro nor is there a metal preference for conferral of DNA binding activity on the purified proteins. When expressed in E. coli, B. japonicum Mur responded to iron, but not manganese, as determined by in vivo promoter occupancy and transcriptional repression activity. Moreover, E. coli Fur activity was manganese-dependent in B. japonicum. Total and chelatable iron levels were higher in E. coli than in B. japonicum under identical growth conditions, and Mur responded to iron in a B. japonicum iron export mutant that accumulated high levels of the metal. However, elevated manganese content in E. coli did not confer activity on Fur or Mur, suggesting a regulatory pool of manganese in B. japonicum that is absent in E. coli. We conclude that the metal selectivity of Mur and Fur depends on the cellular context in which they function, not on intrinsic properties of the proteins. Also, the novel iron sensing mechanism found in the rhizobia may be an evolutionary adaptation to the cellular manganese status. PMID- 26999000 TI - I Know My Story and I Know Your Story: Developing a Conceptual Framework for Vicarious Life Stories. AB - Vicarious life stories are mental representations of other people's life stories. We propose a conceptual framework that situates the study of vicarious life stories at the crossroads between personality and social cognition, identifies their potential functions, and describes possible connections between vicarious and personal life stories. Two preliminary studies compared chapters and specific memories in personal and close others' life stories in two groups of student participants. Ages associated with chapters and specific memories in personal and vicarious life stories showed similar temporal distributions. Emotion ratings of both personal and vicarious life story chapters were related to personality traits and self-esteem, although relations were more consistent for personal chapters. In conclusion, personal and vicarious life stories share important similarities. Mental models of other people include vicarious life stories that serve to expand the self as well as facilitate understanding of others. PMID- 26999001 TI - Strain-level microbial epidemiology and population genomics from shotgun metagenomics. AB - Identifying microbial strains and characterizing their functional potential is essential for pathogen discovery, epidemiology and population genomics. We present pangenome-based phylogenomic analysis (PanPhlAn; http://segatalab.cibio.unitn.it/tools/panphlan), a tool that uses metagenomic data to achieve strain-level microbial profiling resolution. PanPhlAn recognized outbreak strains, produced the largest strain-level population genomic study of human-associated bacteria and, in combination with metatranscriptomics, profiled the transcriptional activity of strains in complex communities. PMID- 26999002 TI - Reprogramming eukaryotic translation with ligand-responsive synthetic RNA switches. AB - Protein synthesis in eukaryotes is regulated by diverse reprogramming mechanisms that expand the coding capacity of individual genes. Here, we exploit one such mechanism, termed -1 programmed ribosomal frameshifting (-1 PRF), to engineer ligand-responsive RNA switches that regulate protein expression. First, efficient -1 PRF stimulatory RNA elements were discovered by in vitro selection; then, ligand-responsive switches were constructed by coupling -1 PRF stimulatory elements to RNA aptamers using rational design and directed evolution in Saccharomyces cerevisiae. We demonstrate that -1 PRF switches tightly control the relative stoichiometry of two distinct protein outputs from a single mRNA, exhibiting consistent ligand response across whole populations of cells. Furthermore, -1 PRF switches were applied to build single-mRNA logic gates and an apoptosis module in yeast. Together, these results showcase the potential for harnessing translation-reprogramming mechanisms for synthetic biology, and they establish -1 PRF switches as powerful RNA tools for controlling protein synthesis in eukaryotes. PMID- 26999003 TI - The role of microRNA-27a/b and microRNA-494 in estrogen-mediated downregulation of tissue factor pathway inhibitor alpha. AB - Essentials Estrogens are known to influence the expression of microRNAs in breast cancer cells. We looked at microRNAs in estrogenic regulation of tissue factor pathway inhibitor alpha (TFPIalpha). Estrogen upregulated microRNA-27a/b and microRNA-494 through the estrogen receptor alpha. MicroRNA-27a/b and microRNA-494 are partly involved in estrogenic downregulation of TFPIalpha. SUMMARY: Background Tissue factor pathway inhibitor (TFPI) has been linked to breast cancer pathogenesis. We have recently reported TFPI mRNA levels to be downregulated by estrogens in a breast cancer cell line (MCF7) through the estrogen receptor alpha (ERalpha). Accumulating evidence also indicates that activation of ERalpha signaling by estrogens may modulate the expression of target genes indirectly through microRNAs (miRNAs). Objectives To examine if miRNAs are involved in the estrogenic downregulation of TFPIalpha. Methods Computational analysis of the TFPI 3'-untranslated region (UTR) identified potential binding sites for miR-19a/b, miR-27a/b, miR-494, and miR-24. Transient overexpression or inhibition of the respective miRNAs was achieved by transfection of miRNA mimics or inhibitors. Direct targeting of TFPI 3'-UTR by miR-27a/b and miR-494 was determined by luciferase reporter assay in HEK293T cells. Effects of 17alpha-ethinylestradiol (EE2) and fulvestrant on relative miR 27a/b, miR-494, and TFPI mRNA levels in MCF7 cells were determined by qRT-PCR and secreted TFPIalpha protein by ELISA. Transient knockdown of ERalpha was achieved by siRNA transfection. Results EE2 treatment lead to a significant increase in miR-19a, miR-27a/b, miR-494, and miR-24 mRNA levels in MCF7 cells through ERalpha. miR-27a/b and miR-494 mimics lead to reduced TFPI mRNA and protein levels. Luciferase assay showed direct targeting of miR-27a/b and miR-494 on TFPI mRNA. Impaired estrogen-mediated downregulation of TFPI mRNA was detected in anti miR-27a/b and anti-miR-494 transfected cells. Conclusions Our results provide evidence that miR-27a/b and miR-494 regulate TFPIalpha expression and suggest a possible role of these miRNAs in the estrogen-mediated downregulation of TFPIalpha. PMID- 26999004 TI - QRS Remodeling to Predict Left Ventricular Reverse Remodeling After Cardiac Resynchronization Therapy. PMID- 26999005 TI - Calix[6]azacryptand Ligand with a Sterically Protected Tren-Based Coordination Site for Metal Ions. AB - A new calix[6]azacryptand ligand has been prepared in six steps starting from 1,3,5-trismethoxycalix[6]arene. An X-ray study shows that this ligand has a sterically protected tren-based binding site at the bottom of a polyaromatic bowl and ether sites around its rim. It binds Zn(2+) to give a complex in which zinc is in a trigonal bipyramidal geometry with a water bound in one apical position and two additional hydrogen-bonded waters that fill the calixarene cavity. PMID- 26999006 TI - Pisa syndrome in a patient with pathologically confirmed Parkinson's disease. PMID- 26999007 TI - Using telemedicine in the care of newborn infants after discharge from a neonatal intensive care unit reduced the need of hospital visits. AB - AIM: This study examined the use of telemedicine as a means to follow up infants discharged from a Swedish neonatal intensive care unit to home health care. METHODS: Families were randomised to either a control group receiving standard home health care (n = 42 families) or a telemedicine group receiving home health care with telemedicine support (n = 47 families) after discharge from the hospital. Both groups had follow-up hospital appointments with the neonatal nurse. In the telemedicine group, appointments were supplemented by the use of a specially designed web page and video calls. RESULTS: The use of the web page and video calls decreased the number of emergency visits to the hospital (p = 0.047). In the telemedicine group, 26% of the families felt they had more scheduled appointments than necessary, whereas only 6% of the families in the control group thought so (p = 0.037). The parents were highly satisfied with the use of telemedicine. Although the nurses were favourable to using telemedicine, the rigid organisation of the home healthcare programme and the nurses' schedules and work routines prevented its optimal use. CONCLUSION: The use of telemedicine decreased the need of hospital visits. Organisational adaptations would be necessary to make the best use of telemedicine. PMID- 26999008 TI - Life History Traits Reflect Changes in Mediterranean Butterfly Communities Due to Forest Encroachment. AB - The biodiversity of the Southern Balkans, part of the Mediterranean global biodiversity hot-spot, is threatened by land use intensification and abandonment, the latter causing forest encroachment of formerly open habitats. We investigated the impact of forest encroachment on butterfly species richness, community species composition and the representation of life history traits by repeated seasonal visits of 150 one-hectare sites in five separate regions in three countries-Greece, Bulgaria, and the Republic of Macedonia (FYROM-the Former Yugoslav Republic of Macedonia)- 10 replicates for each habitat type of grasslands, open formations and scrub forest within each region. Grasslands and open formations sites hosted in average more species and more red-listed species than scrub forest, while no pattern was found for numbers of Mediterranean species. As shown by ordination analyses, each of the three habitat types hosted distinct butterfly communities, with Mediterranean species inclining either towards grasslands or open formations. Analysing the representation of life history traits revealed that successional development from grasslands and open formations towards scrub forest shifts the community composition towards species overwintering in earlier stages, having fewer generations per year, and inhabiting large European or Eurosiberian (e.g. northern) ranges; it decreases the representation of Mediterranean endemics. The loss of grasslands and semi open formations due to forest encroachment thus threatens exactly the species that should be the focus of conservation attention in the Mediterranean region, and innovative conservation actions to prevent ongoing forest encroachment are badly needed. PMID- 26999009 TI - Drivers of Vaginal Drug Delivery System Acceptability from Internet-Based Conjoint Analysis. AB - Vaginal microbicides potentially empower women to protect themselves from HIV and other sexually transmitted infections (STIs), especially when culture, religion, or social status may prevent them from negotiating condom use. The open literature contains minimal information on factors that drive user acceptability of women's health products or vaginal drug delivery systems. By understanding what women find to be most important with regard to sensory properties and product functionality, developers can iteratively formulate a more desirable product. Conjoint analysis is a technique widely used in market research to determine what combination of elements influence a consumer's willingness to try or use a product. We applied conjoint analysis here to better understand what sexually-active woman want in a microbicide, toward our goal of formulating a product that is highly acceptable to women. Both sensory and non-sensory attributes were tested, including shape, color, wait time, partner awareness, messiness/leakage, duration of protection, and functionality. Heterosexually active women between 18 and 35 years of age in the United States (n = 302) completed an anonymous online conjoint survey using IdeaMap software. Attributes (product elements) were systematically presented in various combinations; women rated these combinations of a 9-point willingness-to-try scale. By coupling systematic combinations and regression modeling, we can estimate the unique appeal of each element. In this population, a multifunctional product (i.e., broad spectrum STI protection, coupled with conception) is far more desirable than a microbicide targeted solely for HIV protection; we also found partner awareness and leakage are potentially strong barriers to use. PMID- 26999010 TI - Shensongyangxin Capsules for Paroxysmal Atrial Fibrillation: A Systematic Review of Randomized Clinical Trials. AB - OBJECTIVE: To evaluate the evidence for the effectiveness and safety of Shensongyangxin Capsules (SSYX) for treating paroxysmal atrial fibrillation (PAF). METHODS: We searched for randomized clinical trials for SSYX in PAF up to June 2015. The Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.3 was used to synthesize the results. RESULTS: We included 22 trials involving 2,347 PAF patients. The quality of the included studies was generally poor. The results of the meta-analysis showed that SSYX plus routine treatment was more effective at improving P-wave dispersion (Pwd) and the frequency of PAF attacks compared with routine treatment alone. The results from the included trials that compared SSYX plus routine treatment and arrhythmic drugs plus routine treatment were inconsistent. Trials reported on Pwd, quality of life, frequency of PAF attacks or maintenance rate of sinus rhythm and found that SSYX combined with anti-arrhythmic drugs plus routine treatment was more effective than anti-arrhythmic drugs plus routine treatment. Four of the trials reported adverse events, indicating that SSYX was potentially safer than anti arrhythmic drugs. CONCLUSIONS: There appears to be some benefit from the use of SSYX. However, due to poor methodological quality, we could not draw confirmative conclusions regarding the beneficial effect of using SSYX. PMID- 26999011 TI - Exclusive Breast-feeding Protects against Mother-to-Child Transmission of HIV-1 through 12 Months of Age in Tanzania. AB - The jury on transmission of HIV through breast-feeding is still on. Data from a clinical trial in children born to HIV-positive mothers were evaluated with respect to their relationship to mother-to-child transmission. A total of 1629 infants who were not infected at age 6 weeks, had HIV results available at 12 months and who were breast-fed were included in this study. Exclusive breast feeding (EBF) rates declined from 85% at 2 months to < 30% by 4 months. EBF was associated with a sustained and significant reduction in HIV infection. With every incremental month of EBF, HIV infection was reduced by 16% [multivariable (risk ratio) RR: 0.84, CI: 0.72-0.98, p = 0.03] from enrollment to 6 months of age and by 18% (multivariable RR: 0.82, CI: 0.72-0.94, p = 0.005) from enrollment to 12 months of age. EBF significantly reduces the risk of vertical HIV transmission through 12 months of age. PMID- 26999014 TI - Effect of substrate polishing on the growth of graphene on 3C-SiC(111)/Si(111) by high temperature annealing. AB - We analyse the effects of substrate polishing and of the epilayer thickness on the quality of graphene layers grown by high temperature annealing on 3C SiC(111)/Si(111) by scanning tunnelling microscopy, x-ray photoelectron spectroscopy, Raman spectroscopy, low energy electron diffraction and high resolution angle resolved photoemission spectroscopy. The results provide a comprehensive set of data confirming the superior quality of the graphene layers obtained on polished substrates, and the limitations of the growth obtained on unpolished surfaces. PMID- 26999012 TI - The Effect of Rapid Antigen Detection Test on Antibiotic Prescription Decision of Clinicians and Reducing Antibiotic Costs in Children with Acute Pharyngitis. AB - We aimed to investigate the effect of rapid antigen detection test (RADT) in the diagnosis of streptococcal pharyngitis, its impact on antibiotic prescription decision of pediatricians and influence on reduction of antibiotic treatment costs in children with pharyngitis. The study group consisted of 223 patients who were diagnosed with pharyngitis by pediatricians. The sensitivity and specificity of RADT were 92.1% (95% Cl: 78.6-98.3%) and 97.3% (95% Cl: 93.8-99.1%), respectively. In the first assessment, before performing RADT, pediatricians decided to prescribe antibiotics for 178 (79.8%) patients with pharyngitis. After learning RADT results, pediatricians finally decided to prescribe antibiotics for 83 (37.2%) patients with pharyngitis, and antibiotic prescription decreased by 42.6%. Antibiotic costs in non-Group A streptococcus pharyngitis, Group A streptococcus pharyngitis and all subjects groups decreased by 80.8%, 48%, and 76.4%, respectively. Performing RADT in children with pharyngitis has an important impact on treatment decision of clinicians, reduction of unnecessary antibiotic prescriptions and antibiotic costs. PMID- 26999016 TI - Can Body Mass Index Predict the Difficulty of Colonoscopy? PMID- 26999015 TI - Sodium Glucose Cotransporter 2 (SGLT2) Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells. AB - PURPOSE: Mesangial cells play an important role in regulating glomerular filtration by altering their cellular tone. We report the presence of a sodium glucose cotransporter (SGLT) in rat mesangial cells. This study in rat mesangial cells aimed to evaluate the expression and role of SGLT2. METHODS: The SGLT2 expression in rat mesangial cells was assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Changes in the mesangial cell surface area at different glucose concentrations and the effects of extracellular Na+ and Ca2+ and of SGLT and Na+/Ca2+ exchanger (NCX) inhibitors on cellular size were determined. The cellular sizes and the contractile response were examined during a 6-day incubation with high glucose with or without phlorizin, an SGLT inhibitor. RESULTS: Western blotting revealed an SGLT2 band, and RT-PCR analysis of SGLT2 revealed the predicted 422-bp band in both rat mesangial and renal proximal tubular epithelial cells. The cell surface area changed according to the extracellular glucose concentration. The glucose-induced contraction was abolished by the absence of either extracellular Na+ or Ca2+ and by SGLT and NCX inhibitors. Under the high glucose condition, the cell size decreased for 2 days and increased afterwards; these cells did not contract in response to angiotensin II, and the SGLT inhibitor restored the abolished contraction. CONCLUSIONS: These data suggest that SGLT2 is expressed in rat mesangial cells, acts as a normal physiological glucose sensor and regulates cellular contractility in rat mesangial cells. PMID- 26999017 TI - Chronological Endoscopic and Pathological Observations in Russell Body Duodenitis. AB - A 64-year-old man was found to have a nodule in his right lung. He also complained of nausea and abdominal pain during the clinical course. Esophagogastroduodenoscopy revealed a duodenal ulcer associated with severe stenosis and a suspicion of malignancy. However, three subsequent biopsies revealed no evidence of malignancy. The fourth biopsy showed scattered large eosinophilic cells with an eccentric nucleus, leading to a diagnosis of Russell body duodenitis (RBD). RBD is an extremely rare disease, and little is known about its etiology and clinical course. The pathogenesis of RBD is discussed based on our experience with this case. PMID- 26999018 TI - Melanocytic Nevus on the Rectal Mucosa Removed Using Endoscopic Submucosal Dissection. AB - Melanocytic nevus is the benign proliferation of melanocytes. The most common location of melanocytic nevus is the skin of the extremities; however, there are few case reports of melanocytic nevus at the rectal mucosa. No prior case of malignant melanoma from melanocytic nevus at the rectal mucosa has been reported; therefore, it is unclear whether resection should be performed or close observation is sufficient. However, the potential malignant transformation of melanocytic nevus should be considered, including melanocytic nevus on the rectum. Melanocytic nevus of the skin can be removed by surgical excision; however, due to rare incidence on the mucosa of the gastrointestinal tract, the optimal treatment for rectal melanocytic nevus remains controversial. Here, we report the first case of melanocytic nevus on the rectal mucosa that was removed by endoscopic submucosal dissection. This case report provides useful information about the optimal management of rectal melanocytic nevus. PMID- 26999019 TI - Correction: Baseline Serum Osteopontin Levels Predict the Clinical Effectiveness of Tocilizumab but Not Infliximab in Biologic-Naive Patients with Rheumatoid Arthritis: A Single-Center Prospective Study at 1 Year (the Keio First-Bio Cohort Study). PMID- 26999020 TI - Optimal Soil Eh, pH, and Water Management for Simultaneously Minimizing Arsenic and Cadmium Concentrations in Rice Grains. AB - Arsenic (As) and cadmium (Cd) concentrations in rice grains are a human health concern. We conducted field experiments to investigate optimal conditions of Eh and pH in soil for simultaneously decreasing As and Cd accumulation in rice. Water managements in the experiments, which included continuous flooding and intermittent irrigation with different intervals after midseason drainage, exerted striking effects on the dissolved As and Cd concentrations in soil through changes in Eh, pH, and dissolved Fe(II) concentrations in the soil. Intermittent irrigation with three-day flooding and five-day drainage was found to be effective for simultaneously decreasing the accumulation of As and Cd in grain. The grain As and Cd concentrations were, respectively, linearly related to the average dissolved As and Cd concentrations during the 3 weeks after heading. We propose a new indicator for expressing the degree to which a decrease in the dissolved As or Cd concentration is compromised by the increase in the other. For minimizing the trade-off relationship between As and Cd in rice grains in the field investigated, water management strategies should target the realization of optimal soil Eh of -73 mV and pH of 6.2 during the 3 weeks after heading. PMID- 26999021 TI - Willingness to Pay for Dog Rabies Vaccine and Registration in Ilocos Norte, Philippines (2012). AB - BACKGROUND: The Philippines is one of the developing countries highly affected by rabies. Dog vaccination campaigns implemented through collaborative effort between the government and NGOs have played an important role in successfully reducing the burden of disease within the country. Nevertheless, rabies vaccination of the domestic animal population requires continuous commitment not only from governments and NGOs, but also from local communities that are directly affected by such efforts. To create such long-term sustained programs, the introduction of affordable dog vaccination and registration fees is essential and has been shown to be an important strategy in Bohol, Philippines. The aim of this study, therefore, was to estimate the average amount of money that individuals were willing to pay for dog vaccination and registration in Ilocos Norte, Philippines. This study also investigated some of the determinants of individuals' willingness to pay (WTP). METHODS: A cross-sectional questionnaire was administered to 300 households in 17 municipalities (out of a total of 21) selected through a multi-stage cluster survey technique. At the time of the survey, Ilocos Norte had a population of approximately 568,017 and was predominantly rural. The Contingent Valuation Method was used to elicit WTP for dog rabies vaccination and registration. A 'bidding game' elicitation strategy that aims to find the maximum amount of money individuals were willing to pay was also employed. Data were collected using paper-based questionnaires. Linear regression was used to examine factors influencing participants' WTP for dog rabies vaccination and registration. KEY RESULTS: On average, Ilocos Norte residents were willing to pay 69.65 Philippine Pesos (PHP) (equivalent to 1.67 USD in 2012) for dog vaccination and 29.13PHP (0.70 USD) for dog registration. Eighty-six per cent of respondents were willing to pay the stated amount to vaccinate each of their dogs, annually. This study also found that WTP was influenced by demographic and knowledge factors. Among these, we found that age, income, participants' willingness to commit to pay each year, municipality of residency, knowledge of the signs of rabies in dogs, and number of dogs owed significantly predicted WTP. PMID- 26999022 TI - Physicochemical Study of Viral Nanoparticles at the Air/Water Interface. AB - The assembly of most single-stranded RNA (ssRNA) viruses into icosahedral nucleocapsids is a spontaneous process driven by protein-protein and RNA-protein interactions. The precise nature of these interactions results in the assembly of extremely monodisperse and structurally indistinguishable nucleocapsids. In this work, by using a ssRNA plant virus (cowpea chlorotic mottle virus [CCMV]) as a charged nanoparticle we show that the diffusion of these nanoparticles from the bulk solution to the air/water interface is an irreversible adsorption process. By using the Langmuir technique, we measured the diffusion and adsorption of viral nucleocapsids at the air/water interface at different pH conditions. The pH changes, and therefore in the net surface charge of the virions, have a great influence in the diffusion rate from the bulk solution to the air/water interface. Moreover, assembly of mesoscopic and microscopic viral aggregates at this interface depends on the net surface charge of the virions and the surface pressure. By using Brewster's angle microscopy we characterized these structures at the interface. Most common structures observed were clusters of virions and soap-frothlike micron-size structures. Furthermore, the CCMV films were compressed to form monolayers and multilayers from moderate to high surface pressures, respectively. After transferring the films from the air/water interface onto mica by using the Langmuir-Blodgett technique, their morphology was characterized by atomic force microscopy. These viral monolayers showed closed-packing nano- and microscopic arrangements. PMID- 26999024 TI - Acceptability of older adults as living kidney donors. AB - PURPOSE OF REVIEW: Kidney transplantation from a living kidney donor (LKD) is associated with better long-term survival and quality of life for a patient with end-stage renal disease (ESRD) than dialysis. We reviewed recent literature on the acceptability and outcomes of older adults as LKDs, which may be misunderstood in routine care. RECENT FINDINGS: Studies report that receiving a kidney from an older LKD is associated with worse recipient and graft survival compared with receiving a kidney from a younger LKD, but similar recipient and graft survival to receiving a kidney from a standard criteria deceased donor. A kidney from a younger vs. older LKD results in better graft survival in younger recipients, whereas the graft survival is similar in older recipients. Compared with healthy matched nondonors, older LKDs have a similar risk of death and cardiovascular disease and the absolute risk of ESRD after 15 years remains less than 1%. The estimated predonation and postdonation lifetime risk of ESRD varies by age, sex and race with lower incidences in individuals who are older, female and white (vs. African-American). SUMMARY: Donor and recipient outcomes from several studies support the acceptability of older adults as LKDs. PMID- 26999023 TI - The dual roles of obesity in chronic kidney disease: a review of the current literature. AB - PURPOSE OF REVIEW: Obesity is a major risk factor for the development of de novo chronic kidney disease (CKD). However, once kidney disease is acquired, obesity is paradoxically linked with greater survival, especially in those with advanced CKD. This review examines current evidence for obesity as a risk factor for incident CKD, studies of obesity and mortality across various CKD populations, and potential mechanisms underlying the 'obesity paradox' in kidney disease. RECENT FINDINGS: Large cohort studies show that overweight body habitus, especially in the context of metabolic syndrome, is associated with higher risk of incident CKD. Emerging data also suggest weight-loss interventions retard or reverse early CKD progression, whereas in hemodialysis patients weight-loss paradoxically heralds poor outcomes. Although the pathogenesis of CKD in obesity remains unclear, studies indicate that excess body fat leads to kidney disease via indirect and direct mechanisms. Meta-analyses suggest that overweight and obese BMI ranges are counterintuitively associated with lower mortality in advanced predialysis and dialysis-dependent CKD patients, whereas a pooled analysis observed that higher pretransplantation BMI was associated with higher mortality in kidney transplantation recipients. SUMMARY: In addition to its role as a risk factor for de novo CKD, there appears to be a consistent association between obesity and lower mortality in those with established CKD, particularly among hemodialysis patients, suggesting that the reverse epidemiology of obesity is biologically plausible. PMID- 26999025 TI - Salivary gland morphology, tissue tropism and the progression of tospovirus infection in Frankliniella occidentalis. AB - Tomato spotted wilt virus (TSWV) is transmitted by thrips in a propagative manner; however, progression of virus infection in the insect is not fully understood. The goal of this work was to study the morphology and infection of thrips salivary glands. The primary salivary glands (PSG) are complex, with three distinct regions that may have unique functions. Analysis of TSWV progression in thrips revealed the presence of viral proteins in the foregut, midgut, ligaments, tubular salivary glands (TSG), and efferent duct and filament structures connecting the TSG and PSG of first and second instar larvae. The primary site of virus infection shifted from the midgut and TSG in the larvae to the PSG in adults, suggesting that tissue tropism changes with insect development. TSG infection was detected in advance of PSG infection. These findings support the hypothesis that the TSG are involved in trafficking of TSWV to the PSG. PMID- 26999027 TI - HCV RNA traffic and association with NS5A in living cells. AB - The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3'-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly. PMID- 26999028 TI - Application of carbon foam for heavy metal removal from industrial plating wastewater and toxicity evaluation of the adsorbent. AB - Electroplating wastewater contains various types of toxic substances, such as heavy metals, solvents, and cleaning agents. Carbon foam was used as an adsorbent for the removal of heavy metals from real industrial plating wastewater. Its sorption capacity was compared with those of a commercial ion-exchange resin (BC258) and a heavy metal adsorbent (CupriSorbTM) in a batch system. The experimental carbon foam has a considerably higher sorption capacity for Cr and Cu than commercial adsorbents for acid/alkali wastewater and cyanide wastewater. Additionally, cytotoxicity test showed that the newly developed adsorbent has low cytotoxic effects on three kinds of human cells. In a pilot plant, the carbon foam had higher sorption capacity for Cr (73.64 g kg(-1)) than for Cu (14.86 g kg(-1)) and Ni (7.74 g kg(-1)) during 350 h of operation time. Oxidation pretreatments using UV/hydrogen peroxide enhance heavy metal removal from plating wastewater containing cyanide compounds. PMID- 26999026 TI - Type 1 interferon licenses naive CD8 T cells to mediate anti-viral cytotoxicity. AB - Naive T cells, unlike memory T cells, exhibit very limited effector function in response to cognate antigen, but exposure to type 1 interferon (IFN) prior to cognate antigen allows for rapid manifestation of effector functions. A full assessment of the functions of these IFN-sensitized otherwise naive T cells has not been made, nor has their capacity to be effector cells in vivo. We describe here that IFN-sensitized naive T cells in the absence of cognate antigen adopt a partial activated phenotype distinguished by the upregulation of the surface activation marker CD69, effector-associated transcription factors Eomes and IRF4, and cytotoxicity effector molecule granzyme B. IFN-sensitized naive T cells lysed target cells in vivo and responded to low concentrations and affinities of cognate ligands. We suggest that this rapid and sensitive effector function of IFN-conditioned naive CD8 T cells may play a role in pathogen control and help ward off superinfections. PMID- 26999029 TI - The position of Ghana on the progressive map of positive mental health: A critical perspective. AB - According to the World Health Organisation (WHO), mental health is a state of well-being and not just the absence of diseases. With this definition, there has been a surge of mental health research, albeit still predominantly in Western countries, which is reflected in contemporary theories on positive mental health that include 'flourishing mental health', 'salutogenesis', and 'fortigenesis'. However, in low- and middle-income countries (LMICs), mental health research is slowly receiving scholarly attention. The aim of this paper was twofold: Firstly, to highlight progress that had been made in some LMICs, giving consideration to research across different settings and populations as a basis to argue for more research on positive mental health in the Ghanaian context. Secondly, to present a critical perspective on the current mental health research trends in Ghana, thus discussing important recommendations for future research. PMID- 26999031 TI - Exploring the Association Between Rosacea and Parkinson Disease: A Danish Nationwide Cohort Study. AB - IMPORTANCE: The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss. OBJECTIVE: To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea. DESIGN, SETTING, AND PARTICIPANTS: A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015. MAIN OUTCOMES AND MEASURES: The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models. RESULTS: A total of 5 404 692 individuals were included in the reference population; of these, 22 387 individuals (9812 [43.8%] women; mean [SD] age at diagnosis, 75.9 [10.2] years) received a diagnosis of Parkinson disease during the study period and 68 053 individuals (45 712 [67.2%] women; mean age, 42.2 [16.5] years) were registered as having rosacea. The IRs of Parkinson disease per 10 000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2 fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 [95% CI, 1.67-2.48]), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 [95% CI, 0.97-0.99]). CONCLUSIONS AND RELEVANCE: Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared pathogenic mechanisms involving elevated matrix metalloproteinase activity. The clinical consequences of this association require further study. PMID- 26999032 TI - Magnetic Resonance Imaging measurements of a water spray upstream and downstream of a spray nozzle exit orifice. AB - Sprays are dynamic collections of droplets dispersed in a gas, with many industrial and agricultural applications. Quantitative characterization is essential for understanding processes of spray formation and dynamics. There exists a wide range of measurement techniques to characterize sprays, from direct imaging to phase Doppler interferometry to X-rays, which provide detailed information on spray characteristics in the "far-nozzle" region (?10 diameters of the nozzle). However, traditional methods are limited in their ability to characterize the "near-nozzle" region where the fluid may be inside the nozzle, optically dense, or incompletely atomized. Magnetic Resonance Imaging (MRI) presents potential as a non-invasive technique that is capable of measuring optically inaccessible fluid in a quantitative fashion. In this work, MRI measurements of the spray generated by ceramic flat-fan nozzles were performed. A wide range of flow speeds in the system (0.2 to >25m/s) necessitated short encoding times. A 3D Conical SPRITE and motion-sensitized 3D Conical SPRITE were employed. The signal from water inside the nozzle was well-characterized, both via proton density and velocity measurements. The signal outside the nozzle, in the near-nozzle region, was detectable, corresponding to the expected flat-fan spray pattern up to 3mm away. The results demonstrate the potential of MRI for measuring spray characteristics in areas inaccessible by other methods. PMID- 26999033 TI - Variability of a "force signature" during windmill softball pitching and relationship between discrete force variables and pitch velocity. AB - This study assessed reliability of discrete ground reaction force (GRF) variables over multiple pitching trials, investigated the relationships between discrete GRF variables and pitch velocity (PV) and assessed the variability of the "force signature" or continuous force-time curve during the pitching motion of windmill softball pitchers. Intraclass correlation coefficient (ICC) for all discrete variables was high (0.86-0.99) while the coefficient of variance (CV) was low (1.4-5.2%). Two discrete variables were significantly correlated to PV; second vertical peak force (r(5)=0.81, p=0.03) and time between peak forces (r(5)=-0.79; p=0.03). High ICCs and low CVs support the reliability of discrete GRF and PV variables over multiple trials and significant correlations indicate there is a relationship between the ability to produce force and the timing of this force production with PV. The mean of all pitchers' curve-average standard deviation of their continuous force-time curves demonstrated low variability (CV=4.4%) indicating a repeatable and identifiable "force signature" pattern during this motion. As such, the continuous force-time curve in addition to discrete GRF variables should be examined in future research as a potential method to monitor or explain changes in pitching performance. PMID- 26999034 TI - Longitudinal examination of objectively-measured physical activity and sedentary time among children with and without significant movement impairments. AB - BACKGROUND: Children with Developmental Coordination Disorder (DCD) tend to be less active than typically-developing (TD) children. Current evidence, however, is based on cross-sectional and self-reported activity, and little is known about sedentary time among children with significant movement impairments such as DCD. The current study examines the longitudinal patterns of objectively measured physical activity and sedentary time in children with and without possible DCD (pDCD). METHODS: Data is from a longitudinal nested case-control study, with 103 participants (n=60 males ages=12 and 13 at baseline). Participants averaging ?16th percentile on the Movement Assessment Battery for Children were considered having significant movement impairments and pDCD (n=49). All participants wore accelerometers for seven days. RESULTS: There were significant main effects for time (Estimate=-23.98, p<.01) and gender (Estimate=59.86, p<.05) on total physical activity, and time spent being sedentary (Estimate=15.58, p<.05). Significant main effects for pDCD (Estimate=-5.38, p<.05) and gender (Estimate=26.89, p<.01), and time by gender interaction (Estimate=-7.50, p<.05) were found for moderate-to-vigorous physical activity (MVPA). Sedentary time did not differ between children with and without DCD. CONCLUSIONS: Results suggest children with pDCD engaged in less MVPA compared to TD children. Consistent patterns of MVPA over time, however, suggest that the divergence in MVPA occurs earlier in childhood. Further longitudinal research following a younger cohort is necessary to identify the specific point that differences in MVPA emerge. PMID- 26999035 TI - Conceptualization and assessment of disability in shoulder-specific measures with reference to the International Classification of Functioning, Disability and Health. AB - OBJECTIVE: To expand on a previous systematic review of shoulder-specific outcome measures by investigating how concepts of functioning were conceptualized and measured, using International Classification of Functioning, Disability and Health (ICF) constructs as a reference. METHODS: The material consisted of the linked content of 17 condition-specific measures. The distribution of the key concepts of functioning was assessed in relation to the 3 ICF levels: body level (body functions and structures), personal level (activities) and societal level (participation). Based on this cate-gorization, the concepts were further explored; body functions as to whether they were informed by any contextual information, and activities and participation as to whether they measured a person's capacity, capability or performance. RESULTS: Seven measures assessed all 3 levels of functioning, 8 measured 2 levels, and 2 measured a single level. The majority of the 15 measures including body functions assessed a mix of decontextualized and contextualized functions. Of the 13 measures of activities, 7 measured capabilities, 4 performance and 2 used both constructs. In comparison, among the 11 measures of participation, 5 measured capabilities, 2 performance and 4 a mixture of these. No measure used the capacity construct. CONCLUSION: Shoulder-specific outcome measures differ in their choice of measurement levels and measurement constructs. The inconsistent use of the capability and performance constructs to measure activities and participation, raise important questions about the suitability of the measures for their intended use. PMID- 26999036 TI - Bone Metastases of Hepatocellular Carcinoma: Appearance on MRI Using a Standard Abdominal Protocol. AB - OBJECTIVE: The purpose of this study is to describe the MRI features of hepatocellular carcinoma (HCC) bone metastases. MATERIALS AND METHODS: Thirty three consecutive patients were included. Two radiologists performed qualitative and quantitative analysis. The coordinator searched for clinical and epidemiologic features related to patients and their primary liver tumors. Earlier MRI studies were also reviewed to determine whether bone metastases were already present and prospectively identified. Descriptive statistics and the Lin concordance correlation coefficient were used. RESULTS: Chronic hepatitis C virus infection was the most common cause of liver disease (20/32; 62.5%), and diffuse and multifocal HCC were the most frequent types of liver HCCs (28/33; 84.8%). Most lesions were located at the spine (109/155; 70.3%), with high signal intensity on fat-suppressed T1-weighted (54/62; 87.1%) and T2-weighted (53/62; 85.5%) images. Bone metastases were predominantly nodular (48/62; 77.4%), confined to the vertebral body (40/60; 66.7%), and best visualized at the arterial phase (40/62; 64.5%). The ring pattern of enhancement was present in 23 of 62 lesions, and the remaining lesions showed diffuse enhancement. Thirty-five of 62 (56.4%) bone metastases showed arterial peak of enhancement. In 13 of 33 (39.9%) patients, bone metastases were not prospectively reported. CONCLUSION: Most patients with bone metastases had chronic hepatitis C virus infection and diffuse or multifocal HCC. Metastases are most commonly appreciated as hypervascular focal moderately intensely enhancing nodular masses on the hepatic arterial dominant phase images, with concomitant moderately high signal intensity on fat-suppressed T1- and T2-weighted images. PMID- 26999037 TI - Pharmacokinetic comparisons of Paeoniflorin and Paeoniflorin-6'O-benzene sulfonate in rats via different routes of administration. AB - 1. The pharmacokinetics study of Paeoniflorin (Pae) and its acylated derivative (CP-25) was performed. 2. The structure of CP-25 was identified by mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). The rats were injected with CP-25(6, 12, 24 mg/kg) and orally treated with CP-25 (32, 64, 128 mg/kg), respectively. An high-performance liquid chromatography (HPLC) assay was developed to determine the plasma concentrations of Pae and CP-25. 3. The results of MS and NMR showed that the acylated product was Pae-6'O-benzene sulfonate (CP-25). The plasma levels in oral CP-25 groups were detectable, whereas those of Pae in the oral groups (25 and 50 mg/kg) were undetectable. More specifically, the Cmax values of oral CP-25 were 0.12, 0.19 and 0.44 MUg/ml, and the corresponding t1/2beta of CP-25 were 1.44, 2.12 and 2.11 h, respectively. In addition, the t1/2beta values of intravenous CP-25 were 161.99, 152.81 and 153.76 min, respectively. 4. Compared with the venous pharmacokinetics parameters of Pae, those of the t1/2beta, MRT, Vd and CL/F in the CP-25 groups increased noticeably. As expected, compared with oral parameters of Pae, those of t1/2a, t1/2beta, AUC, MRT and Vd in the CP-25 group increased obviously. Finally, the absolute bioavailability of Pae and CP-25 were 3.6 and 10.6%, respectively. 5. Our results indicate that CP-25 is characterized by improved absorption, well distribution, lower clearance, long mean residence time, and moderate bioavailability in rats. PMID- 26999038 TI - Could chest wall rigidity be a factor in rapid death from illicit fentanyl abuse? AB - BACKGROUND: There has been a significant spike in fentanyl-related deaths from illicit fentanyl supplied via the heroin trade. Past fentanyl access was primarily oral or dermal via prescription fentanyl patch diversion. One factor potentially driving this increase in fatalities is the change in route of administration. Rapid intravenous (IV) fentanyl can produce chest wall rigidity. We evaluated post-mortem fentanyl and norfentanyl concentrations in a recent surge of lethal fentanyl intoxications. METHODS: Fentanyl related deaths from the Franklin County coroner's office from January to September 2015 were identified. Presumptive positive fentanyl results were confirmed by quantitative analysis using liquid chromatography tandem mass spectrometry (LC/MS/MS) and were able to quantify fentanyl, norfentanyl, alfentanyl, and sufentanyl. RESULTS: 48 fentanyl deaths were identified. Mean fentanyl concentrations were 12.5 ng/ml, (range 0.5 ng/ml to >40 ng/ml). Mean norfentanyl concentrations were 1.9 ng/ml (range none detected to 8.3 ng/ml). No appreciable concentrations of norfentanyl could be detected in 20 of 48 cases (42%) and were less than 1 ng/ml in 25 cases (52%). Elevated fentanyl concentrations did not correlate with rises in norfentanyl levels. In several cases fentanyl concentrations were strikingly high (22 ng/ml and 20 ng/ml) with no norfentanyl detected. DISCUSSION: The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity. An alternate explanation could be a dose related rapid onset of respiratory arrest. Deaths occurred with low levels of fentanyl in the therapeutic range (1-2 ng/ml) in apparent non-naive opiate abusers. Acute chest wall rigidity is a well-recognized complication in the medical community but unknown within the drug abuse community. The average abuser of illicit opioids may be unaware of the increasing fentanyl content of their illicit opioid purchase. CONCLUSION: In summary we believe sudden onset chest wall rigidity may be a significant and previously unreported factor leading to an increased mortality, from illicit IV fentanyl use. Fentanyl and norfentanyl ratios and concentrations suggest a more rapid onset of death given the finding of fentanyl without norfentanyl in many of the fatalities. Chest wall rigidity may help explain the cause of death in these instances, in contrast to the typical opioid-related overdose deaths. Intravenous heroin users should be educated regarding this potentially fatal complication given the increasingly common substitution and combination with heroin of fentanyl. PMID- 26999039 TI - Antioxidant compounds from the stem bark of Garcinia atroviridis. AB - A new xanthone, namely garcinexanthone G (1), along with eight known compounds, stigmasta-5,22-dien-3beta-ol (2), stigmasta-5,22-dien-3-O-beta-glucopyranoside (3), 3beta-acetoxy-11alpha,12alpha-epoxyoleanan-28,13beta-olide (4), 2,6 dimethoxy-p-benzoquinone (5), 1,3,5-trihydroxy-2-methoxyxanthone (6), 1,3,7 trihydroxyxanthone (7), kaempferol (8) and quercetin (9), were isolated from the stem bark of Garcinia atroviridis. Their structures were elucidated based on spectroscopic methods including nuclear magnetic resonance (NMR-1D and 2D), UV, IR, and mass spectrometry. All the isolated compounds were evaluated for their antioxidant properties based on the DPPH radical scavenging activities. Results showed that 1,3,7-trihydroxyxanthone and quercetin showed significant antioxidant activities with EC50 values of 16.20 and 12.68 MUg/ml, respectively, as compared to the control, ascorbic acid (7.4 MUg/ml). PMID- 26999040 TI - Analysis of clinical characteristics and outcome of patients with previously untreated diffuse large B-cell lymphoma and renal involvement in the rituximab era. AB - Renal involvement in patients with lymphoma is rare but associated with poor prognosis. We analyzed characteristics and outcome of 22 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and renal involvement treated with a rituximab-containing regimen in curative intent. The majority of patients presented in advanced disease, 86% were Ann Arbor stage >= III and had an IPI score >= 3. Renal impairment was present in 32%. Outcome was poor with three-year progression-free survival (PFS) 44% and three-year overall survival (OS) 52% and significantly worse compared to DLBCL without renal involvement (p < 0.01). Patients with high-risk IPI had a significantly inferior prognosis compared to intermediate-risk IPI (three-year OS 0% vs. 75%, p = 0.01) as did those with renal impairment. A high rate of central nervous system (CNS) relapse (8/22) was observed. Intravenous high-dose methotrexate and intrathecal therapy showed a trend toward prolonged time to CNS relapse. Implementation of CNS prophylaxis might therefore be considered in these high-risk patients. PMID- 26999042 TI - A noble and single source precursor for the synthesis of metal-rich sulphides embedded in an N-doped carbon framework for highly active OER electrocatalysts. AB - Here, we demonstrate a green and environment-friendly pyrolysis route for the synthesis of metal-rich sulphide embedded in an N-doped carbon (NC) framework in the absence of sulphide ions (S(2-)). The metal-chelate complex (tris(ethylenediamine) metal(ii) sulfate) serves as a new and single source precursor for the synthesis of earth abundant and non-precious hybrid structures such as metal-rich sulphides Co9S8@NC and Ni3S2@NC when M(II) = Co(2+) and Ni(2+) and counter sulphate (SO4(2-)) ions are the source of S. Both the hybrids show superior OER activity as compared to commercial RuO2. PMID- 26999041 TI - Unimodality and Multimodality Cryodebridement for Airway Obstruction. A Single Center Experience with Safety and Efficacy. AB - RATIONALE: Cryodebridement (CD) refers to the removal of obstructive material from the lumen of the tracheobronchial tree by freezing with a cryoprobe, which is usually inserted through a flexible bronchoscope. This method of achieving instant recanalization of airways has been established for over 20 years, but published experience comprises limited case series. OBJECTIVES: This study describes a single large-volume referral center experience, including clinical outcomes and safety profile. METHODS: Electronic medical records of 156 patients who underwent bronchoscopic CD between December 2007 and March 2012 as the primary method to relieve airway obstruction were reviewed retrospectively. MEASUREMENTS AND MAIN RESULTS: The most frequent cause of airway obstruction was malignancy (n = 88), with non-small-cell lung cancer and metastatic renal cell carcinoma being the most common etiologies. The site of obstruction was localized to the central airways in 63 patients (40%) and the distal airways in 44 patients (28%), and it was diffuse in 49 patients (32%). Bronchoscopic airway patency was achieved in 95% of patients, with the highest success rates found in those with obstruction localized in the central airways. Improvement in symptoms occurred in 118 (82%) of 144 symptomatic patients. Serious complications were reported in 17 patients (11%) and included respiratory distress, severe bleeding, airway injury, and hemodynamic instability. All patients responded to treatment, and no intra- or postoperative deaths were reported. CONCLUSIONS: CD, when used alone or in combination with other endoscopic treatment modalities, appears to be safe and effective in treating endoluminal airway obstruction. PMID- 26999043 TI - Microdroplet-Based Potentiometric Redox Measurements on Gold Nanoporous Electrodes. AB - Potentiometric redox measurements were made in subnanoliter droplets of solutions using an optically transparent nanoporous gold electrode strategically mounted on the stage of an inverted microscope. Nanoporous gold was prepared via dealloying gold leaf with concentrated nitric acid and was chemisorbed to a standard microscope coverslip with (3-mercaptopropyl)trimethoxysilane. The gold surface was further modified with 1-hexanethiol to optimize hydrophobicity of the surface to allow for redox measurements to be made in nanoscopic volumes. Time traces of the open-circuit potential (OCP) were used to construct Nernst plots to evaluate the applicability of the droplet-based potentiometric redox measurement system. Two poised one-electron transfer systems (potassium ferricyanide/ferrocyanide and ferrous/ferric ammonium sulfate) yielded Nernstian slopes of -58.5 and -60.3 mV, respectively, with regression coefficients greater than 0.99. The y-intercepts of the two agreed well to the formal potential of the two standard oxidation reduction potential (ORP) calibrants, ZoBell's and Light's solution. The benzoquinone and hydroquinone redox couple was examined as a representative two electron redox system; a Nernst slope of -30.8 mV was obtained. Additionally, two unpoised systems (potassium ferricyanide and ascorbic acid) were studied to evaluate the system under conditions where only one form of the redox couple is present in appreciable concentrations. Again, slopes near the Nernstian values of -59 and -29 mV, respectively, were obtained. All experiments were carried out using solution volumes between 280 and 1400 pL with injection volumes between 8 and 100 pL. The miniscule volumes allowed for extremely rapid mixing (<305 ms) as well. The small volumes and rapid mixing along with the high accuracy and sensitivity of these measurements lend support to the use of this approach in applications where time is a factor and only small volumes are available for testing. PMID- 26999044 TI - A Flavin-Dependent Decarboxylase-Dehydrogenase-Monooxygenase Assembles the Warhead of alpha,beta-Epoxyketone Proteasome Inhibitors. AB - The alpha,beta-epoxyketone proteasome inhibitor TMC-86A was discovered as a previously unreported metabolite of Streptomyces chromofuscus ATCC49982, and the gene cluster responsible for its biosynthesis was identified via genome sequencing. Incorporation experiments with [(13)C-methyl]l-methionine implicated an alpha-dimethyl-beta-keto acid intermediate in the biosynthesis of TMC-86A. Incubation of the chemically synthesized alpha-dimethyl-beta-keto acid with a purified recombinant flavin-dependent enzyme that is conserved in all known pathways for epoxyketone biosynthesis resulted in formation of the corresponding alpha-methyl-alpha,beta-epoxyketone. This transformation appears to proceed via an unprecedented decarboxylation-dehydrogenation-monooxygenation cascade. The biosynthesis of the TMC-86A warhead is completed by cytochrome P450-mediated hydroxylation of the alpha-methyl-alpha,beta-epoxyketone. PMID- 26999045 TI - Generalisability and Cost-Impact of Antibiotic-Impregnated Central Venous Catheters for Reducing Risk of Bloodstream Infection in Paediatric Intensive Care Units in England. AB - BACKGROUND: We determined the generalisability and cost-impact of adopting antibiotic-impregnated CVCs in all paediatric intensive care units (PICUs) in England, based on results from a large randomised controlled trial (the CATCH trial; ISRCTN34884569). METHODS: BSI rates using standard CVCs were estimated through linkage of national PICU audit data (PICANet) with laboratory surveillance data. We estimated the number of BSI averted if PICUs switched from standard to antibiotic-impregnated CVCs by applying the CATCH trial rate-ratio (0.40; 95% CI 0.17,0.97) to the BSI rate using standard CVCs. The value of healthcare resources made available by averting one BSI as estimated from the trial economic analysis was L10,975; 95% CI -L2,801,L24,751. RESULTS: The BSI rate using standard CVCs was 4.58 (95% CI 4.42,4.74) per 1000 CVC-days in 2012. Applying the rate-ratio gave 232 BSI averted using antibiotic CVCs. The additional cost of purchasing antibiotic-impregnated compared with standard CVCs was L36 for each child, corresponding to additional costs of L317,916 for an estimated 8831 CVCs required in PICUs in 2012. Based on 2012 BSI rates, management of BSI in PICUs cost L2.5 million annually (95% uncertainty interval: L160,986, L5,603,005). The additional cost of antibiotic CVCs would be less than the value of resources associated with managing BSI in PICUs with standard BSI rates >1.2 per 1000 CVC-days. CONCLUSIONS: The cost of introducing antibiotic impregnated CVCs is less than the cost associated with managing BSIs occurring with standard CVCs. The long-term benefits of preventing BSI could mean that antibiotic CVCs are cost-effective even in PICUs with extremely low BSI rates. PMID- 26999047 TI - Reflecting on explanatory ability: A mechanism for detecting gaps in causal knowledge. AB - People frequently overestimate their understanding-with a particularly large blind-spot for gaps in their causal knowledge. We introduce a metacognitive approach to reducing overestimation, termed reflecting on explanatory ability (REA), which is briefly thinking about how well one could explain something in a mechanistic, step-by-step, causally connected manner. Nine experiments demonstrated that engaging in REA just before estimating one's understanding substantially reduced overestimation. Moreover, REA reduced overestimation with nearly the same potency as generating full explanations, but did so 20 times faster (although only for high complexity objects). REA substantially reduced overestimation by inducing participants to quickly evaluate an object's inherent causal complexity (Experiments 4-7). REA reduced overestimation by also fostering step-by-step, causally connected processing (Experiments 2 and 3). Alternative explanations for REA's effects were ruled out including a general conservatism account (Experiments 4 and 5) and a covert explanation account (Experiment 8). REA's overestimation-reduction effect generalized beyond objects (Experiments 1 8) to sociopolitical policies (Experiment 9). REA efficiently detects gaps in our causal knowledge with implications for improving self-directed learning, enhancing self-insight into vocational and academic abilities, and even reducing extremist attitudes. PMID- 26999046 TI - Episodic memories predict adaptive value-based decision-making. AB - Prior research illustrates that memory can guide value-based decision-making. For example, previous work has implicated both working memory and procedural memory (i.e., reinforcement learning) in guiding choice. However, other types of memories, such as episodic memory, may also influence decision-making. Here we test the role for episodic memory-specifically item versus associative memory-in supporting value-based choice. Participants completed a task where they first learned the value associated with trial unique lotteries. After a short delay, they completed a decision-making task where they could choose to reengage with previously encountered lotteries, or new never before seen lotteries. Finally, participants completed a surprise memory test for the lotteries and their associated values. Results indicate that participants chose to reengage more often with lotteries that resulted in high versus low rewards. Critically, participants not only formed detailed, associative memories for the reward values coupled with individual lotteries, but also exhibited adaptive decision-making only when they had intact associative memory. We further found that the relationship between adaptive choice and associative memory generalized to more complex, ecologically valid choice behavior, such as social decision-making. However, individuals more strongly encode experiences of social violations-such as being treated unfairly, suggesting a bias for how individuals form associative memories within social contexts. Together, these findings provide an important integration of episodic memory and decision-making literatures to better understand key mechanisms supporting adaptive behavior. PMID- 26999049 TI - Synthesis and Self-Assembly of Discrete Dimethylsiloxane-Lactic Acid Diblock Co oligomers: The Dononacontamer and Its Shorter Homologues. AB - Most of the theoretical and computational descriptions of the phase behavior of block copolymers describe the chain ensembles of perfect and uniform polymers. In contrast, experimental studies on block copolymers always employ materials with disperse molecular makeup. Although most polymers are so-called monodisperse, they still have a molecular weight dispersity. Here, we describe the synthesis and properties of a series of discrete length diblock co-oligomers, based on oligo-dimethylsiloxane (oDMS) and oligo-lactic acid (oLA), diblock co-oligomers with highly noncompatible blocks. By utilizing an iterative synthetic protocol, co-oligomers with molar masses up to 6901 Da, ultralow molar mass dispersities (D <= 1.00002), and unique control over the co-oligomer composition are synthesized and characterized. This specific block co-oligomer required the development of a new divergent strategy for the oDMS structures by which both bis- and monosubstituted oDMS derivatives up to 59 Si-atoms became available. The incompatibility of the two blocks makes the final coupling more demanding the longer the blocks become. These optimized synthetic procedures granted access to multigram quantities of most of the block co-oligomers, useful to study the lower limits of block copolymer phase segregation in detail. Cylindrical, gyroid, and lamellar nanostructures, as revealed by DSC, SAXS, and AFM, were generated. The small oligomeric size of the block co-oligomers resulted in exceptionally small feature sizes (down to 3.4 nm) and long-range organization. PMID- 26999048 TI - High-Throughput Microdissection for Next-Generation Sequencing. AB - Precision medicine promises to enhance patient treatment through the use of emerging molecular technologies, including genomics, transcriptomics, and proteomics. However, current tools in surgical pathology lack the capability to efficiently isolate specific cell populations in complex tissues/tumors, which can confound molecular results. Expression microdissection (xMD) is an immuno based cell/subcellular isolation tool that procures targets of interest from a cytological or histological specimen. In this study, we demonstrate the accuracy and precision of xMD by rapidly isolating immunostained targets, including cytokeratin AE1/AE3, p53, and estrogen receptor (ER) positive cells and nuclei from tissue sections. Other targets procured included green fluorescent protein (GFP) expressing fibroblasts, in situ hybridization positive Epstein-Barr virus nuclei, and silver stained fungi. In order to assess the effect on molecular data, xMD was utilized to isolate specific targets from a mixed population of cells where the targets constituted only 5% of the sample. Target enrichment from this admixed cell population prior to next-generation sequencing (NGS) produced a minimum 13-fold increase in mutation allele frequency detection. These data suggest a role for xMD in a wide range of molecular pathology studies, as well as in the clinical workflow for samples where tumor cell enrichment is needed, or for those with a relative paucity of target cells. PMID- 26999051 TI - Intra-Rater, Inter-Rater and Test-Retest Reliability of an Instrumented Timed Up and Go (iTUG) Test in Patients with Parkinson's Disease. AB - BACKGROUND: The "Timed Up and Go" (TUG) is a widely used measure of physical functioning in older people and in neurological populations, including Parkinson's Disease. When using an inertial sensor measurement system (instrumented TUG [iTUG]), the individual components of the iTUG and the trunk kinematics can be measured separately, which may provide relevant additional information. OBJECTIVE: The aim of this study was to determine intra-rater, inter rater and test-retest reliability of the iTUG in patients with Parkinson's Disease. METHODS: Twenty eight PD patients, aged 50 years or older, were included. For the iTUG the DynaPort Hybrid (McRoberts, The Hague, The Netherlands) was worn at the lower back. The device measured acceleration and angular velocity in three directions at a rate of 100 samples/s. Patients performed the iTUG five times on two consecutive days. Repeated measurements by the same rater on the same day were used to calculate intra-rater reliability. Repeated measurements by different raters on the same day were used to calculate intra-rater and inter-rater reliability. Repeated measurements by the same rater on different days were used to calculate test-retest reliability. RESULTS: Nineteen ICC values (15%) were >= 0.9 which is considered as excellent reliability. Sixty four ICC values (49%) were >= 0.70 and < 0.90 which is considered as good reliability. Thirty one ICC values (24%) were >= 0.50 and < 0.70, indicating moderate reliability. Sixteen ICC values (12%) were >= 0.30 and < 0.50 indicating poor reliability. Two ICT values (2%) were < 0.30 indicating very poor reliability. CONCLUSIONS: In conclusion, in patients with Parkinson's disease the intra-rater, inter-rater, and test-retest reliability of the individual components of the instrumented TUG (iTUG) was excellent to good for total duration and for turning durations, and good to low for the sub durations and for the kinematics of the SiSt and StSi. The results of this fully automated analysis of instrumented TUG movements demonstrate that several reliable TUG parameters can be identified that provide a basis for a more precise, quantitative use of the TUG test, in clinical practice. PMID- 26999050 TI - A Novel Approach for Ovine Primary Alveolar Epithelial Type II Cell Isolation and Culture from Fresh and Cryopreserved Tissue Obtained from Premature and Juvenile Animals. AB - The in vivo ovine model provides a clinically relevant platform to study cardiopulmonary mechanisms and treatments of disease; however, a robust ovine primary alveolar epithelial type II (ATII) cell culture model is lacking. The objective of this study was to develop and optimize ovine lung tissue cryopreservation and primary ATII cell culture methodologies for the purposes of dissecting mechanisms at the cellular level to elucidate responses observed in vivo. To address this, we established in vitro submerged and air-liquid interface cultures of primary ovine ATII cells isolated from fresh or cryopreserved lung tissues obtained from mechanically ventilated sheep (128 days gestation-6 months of age). Presence, abundance, and mRNA expression of surfactant proteins was assessed by immunocytochemistry, Western Blot, and quantitative PCR respectively on the day of isolation, and throughout the 7 day cell culture study period. All biomarkers were significantly greater from cells isolated from fresh than cryopreserved tissue, and those cultured in air-liquid interface as compared to submerged culture conditions at all time points. Surfactant protein expression remained in the air-liquid interface culture system while that of cells cultured in the submerged system dissipated over time. Despite differences in biomarker magnitude between cells isolated from fresh and cryopreserved tissue, cells isolated from cryopreserved tissue remained metabolically active and demonstrated a similar response as cells from fresh tissue through 72 hr period of hyperoxia. These data demonstrate a cell culture methodology using fresh or cryopreserved tissue to support study of ovine primary ATII cell function and responses, to support expanded use of biobanked tissues, and to further understanding of mechanisms that contribute to in vivo function of the lung. PMID- 26999052 TI - A Zebrafish Larval Model to Assess Virulence of Porcine Streptococcus suis Strains. AB - Streptococcus suis is an encapsulated Gram-positive bacterium, and the leading cause of sepsis and meningitis in young pigs resulting in considerable economic losses in the porcine industry. It is also considered an emerging zoonotic agent. In the environment, both avirulent and virulent strains occur in pigs, and virulent strains appear to cause disease in both humans and pigs. There is a need for a convenient, reliable and standardized animal model to assess S. suis virulence. A zebrafish (Danio rerio) larvae infection model has several advantages, including transparency of larvae, low cost, ease of use and exemption from ethical legislation up to 6 days post fertilization, but has not been previously established as a model for S. suis. Microinjection of different porcine strains of S. suis in zebrafish larvae resulted in highly reproducible dose- and strain-dependent larval death, strongly correlating with presence of the S. suis capsule and to the original virulence of the strain in pigs. Additionally we compared the virulence of the two-component system mutant of ciaRH, which is attenuated for virulence in both mice and pigs in vivo. Infection of larvae with the DeltaciaRH strain resulted in significantly higher survival rate compared to infection with the S10 wild-type strain. Our data demonstrate that zebrafish larvae are a rapid and reliable model to assess the virulence of clinical porcine S. suis isolates. PMID- 26999054 TI - Identifying predictive markers for personalized treatment selection. AB - It is now well recognized that the effectiveness and potential risk of a treatment often vary by patient subgroups. Although trial-and-error and one-size fits-all approaches to treatment selection remain a common practice, much recent focus has been placed on individualized treatment selection based on patient information (La Thangue and Kerr, 2011; Ong et al., 2012). Genetic and molecular markers are becoming increasingly available to guide treatment selection for various diseases including HIV and breast cancer (Mallal et al., 2008; Zujewski and Kamin, 2008). In recent years, many statistical procedures for developing individualized treatment rules (ITRs) have been proposed. However, less focus has been given to efficient selection of predictive biomarkers for treatment selection. The standard Wald test for interactions between treatment and the set of markers of interest may not work well when the marker effects are nonlinear. Furthermore, interaction-based test is scale dependent and may fail to capture markers useful for predicting individualized treatment differences. In this article, we propose to overcome these difficulties by developing a kernel machine (KM) score test that can efficiently identify markers predictive of treatment difference. Simulation studies show that our proposed KM-based score test is more powerful than the Wald test when there is nonlinear effect among the predictors and when the outcome is binary with nonlinear link functions. Furthermore, when there is high-correlation among predictors and when the number of predictors is not small, our method also over-performs Wald test. The proposed method is illustrated with two randomized clinical trials. PMID- 26999055 TI - Spectacular Rate Enhancement of the Diels-Alder Reaction at the Ionic Liquid/n Hexane Interface. AB - The use of the ionic liquid/n-hexane interface as a new class of reaction medium for the Diels-Alder reaction gives large rate enhancements of the order of 10(6) to 10(8) times and high stereoselectivity, as compared to homogeneous media. The rate enhancement is attributed to the H-bonding abilities and polarities of the ionic liquids, whereas the hydrophobicity of ionic liquids was considered to be the factor in controlling stereoselectivity. PMID- 26999053 TI - Objectively Measured Physical Activity in European Adults: Cross-Sectional Findings from the Food4Me Study. AB - BACKGROUND: Comparisons of objectively measured physical activity (PA) between residents of European countries measured concurrently with the same protocol are lacking. We aimed to compare PA between the seven European countries involved in the Food4Me Study, using accelerometer data collected remotely via the Internet. METHODS: Of the 1607 participants recruited, 1287 (539 men and 748 women) provided at least 3 weekdays and 2 weekend days of valid accelerometer data (TracmorD) at baseline and were included in the present analyses. RESULTS: Men were significantly more active than women (physical activity level = 1.74 vs. 1.70, p < 0.001). Time spent in light PA and moderate PA differed significantly between countries but only for women. Adherence to the World Health Organization recommendation to accumulate at least 150 min of moderate-equivalent PA weekly was similar between countries for men (range: 54-65%) but differed significantly between countries for women (range: 26-49%). Prevalence estimates decreased substantially for men and women in all seven countries when PA guidelines were defined as achieving 30 min of moderate and vigorous PA per day. CONCLUSIONS: We were able to obtain valid accelerometer data in real time via the Internet from 80% of participants. Although our estimates are higher compared with data from Sweden, Norway, Portugal and the US, there is room for improvement in PA for all countries involved in the Food4Me Study. PMID- 26999056 TI - Cetuximab as First-line Treatment for Metastatic Colorectal Cancer: Caution With Interpretation of Cost-Effectiveness Results Toward Medical Decision Making. PMID- 26999058 TI - Efficient Strategy for the Construction of Both Enantiomers of the Octahydropyrroloquinolinone Ring System: Total Synthesis of (+)-Aspidospermidine. AB - An efficient and highly stereoselective intramolecular [3 + 2] cycloaddition of nonstabilized azomethine ylide generated from a designed bicyclic aminal precursor is reported for the synthesis of both (-)- and (+) octahydropyrroloquinolinone. One of the enantiomers is further advanced to accomplish the total synthesis of (+)-aspidospermidine. PMID- 26999057 TI - Risk Factors for Bartonella species Infection in Blood Donors from Southeast Brazil. AB - Bacteria from the genus Bartonella are emerging blood-borne bacteria, capable of causing long-lasting infection in marine and terrestrial mammals, including humans. Bartonella are generally well adapted to their main host, causing persistent infection without clinical manifestation. However, these organisms may cause severe disease in natural or accidental hosts. In humans, Bartonella species have been detected from sick patients presented with diverse disease manifestations, including cat scratch disease, trench fever, bacillary angiomatosis, endocarditis, polyarthritis, or granulomatous inflammatory disease. However, with the advances in diagnostic methods, subclinical bloodstream infection in humans has been reported, with the potential for transmission through blood transfusion been recently investigated by our group. The objective of this study was to determine the risk factors associated with Bartonella species infection in asymptomatic blood donors presented at a major blood bank in Southeastern Brazil. Five hundred blood donors were randomly enrolled and tested for Bartonella species infection by specialized blood cultured coupled with high sensitive PCR assays. Epidemiological questionnaires were designed to cover major potential risk factors, such as age, gender, ethnicity, contact with companion animals, livestock, or wild animals, bites from insects or animal, economical status, among other factors. Based on multivariate logistic regression, bloodstream infection with B. henselae or B. clarridgeiae was associated with cat contact (adjusted OR: 3.4, 95% CI: 1.1-9.6) or history of tick bite (adjusted OR: 3.7, 95% CI: 1.3-13.4). These risk factors should be considered during donor screening, as bacteremia by these Bartonella species may not be detected by traditional laboratory screening methods, and it may be transmitted by blood transfusion. PMID- 26999060 TI - CsI as Multifunctional Redox Mediator for Enhanced Li-Air Batteries. AB - We introduce CsI as a multifunctional redox mediator to enhance the performance of Li-air batteries. CsI dissolved in the electrolyte is ionized into Cs(+) and I(-), which perform their roles in the Li anode and air electrode, respectively. The I(-) ions in the electrolyte facilitate the dissolution of Li2O2 in the air electrode as a redox mediator, which reduces the overpotential of the cell. The low overpotential also leads to the suppression of parasitic reactions occurring in the high-voltage range, such as the decomposition of the electrolyte and the reaction between Li2O2 and carbon. At the same time, the Cs(+) ions act as an electrostatic shield at the sharp points of the Li anode, hindering the growth of Li dendrite. The combined effects of reduced parasitic reactions and hindered Li dendrite growth successfully improve the cyclic performance of Li-air cells. PMID- 26999059 TI - Shape-Controlled Deterministic Assembly of Nanowires. AB - Large-scale, deterministic assembly of nanowires and nanotubes with rationally controlled geometries could expand the potential applications of one-dimensional nanomaterials in bottom-up integrated nanodevice arrays and circuits. Control of the positions of straight nanowires and nanotubes has been achieved using several assembly methods, although simultaneous control of position and geometry has not been realized. Here, we demonstrate a new concept combining simultaneous assembly and guided shaping to achieve large-scale, high-precision shape controlled deterministic assembly of nanowires. We lithographically pattern U-shaped trenches and then shear transfer nanowires to the patterned substrate wafers, where the trenches serve to define the positions and shapes of transferred nanowires. Studies using semicircular trenches defined by electron-beam lithography yielded U-shaped nanowires with radii of curvature defined by inner surface of the trenches. Wafer-scale deterministic assembly produced U-shaped nanowires for >430,000 sites with a yield of ~90%. In addition, mechanistic studies and simulations demonstrate that shaping results in primarily elastic deformation of the nanowires and show clearly the diameter-dependent limits achievable for accessible forces. Last, this approach was used to assemble U shaped three-dimensional nanowire field-effect transistor bioprobe arrays containing 200 individually addressable nanodevices. By combining the strengths of wafer-scale top-down fabrication with diverse and tunable properties of one dimensional building blocks in novel structural configurations, shape-controlled deterministic nanowire assembly is expected to enable new applications in many areas including nanobioelectronics and nanophotonics. PMID- 26999061 TI - Comminuted long bone fractures in children. Could combined fixation improve the results? AB - Comminuted diaphyseal fractures in the pediatric age group represent a major orthopedic problem. It is associated with a high incidence of complications and poor outcomes because of the instability and difficulty in treatment. The aim of this study was to evaluate the efficacy of combined external skeletal fixation and flexible intramedullary nails in reconstruction of comminuted diaphyseal fracture in skeletally immature patients. Combined external fixator and elastic stable intramedullary nails were used in the management of 27 pediatric patients (15 males and 12 females) with unstable comminuted diaphyseal fractures of the tibia and femur. There were 19 fractures of the femur and eight fractures of the tibia. The average age of the patients was 8.7 years (range 7-14 years) for the femur and 10.8 years (range 6-15 years) for the tibia. Fractures were classified according to the system of Winquist and Hansen as grade II (five cases), grade III (nine cases), and grade IV (13 cases). All cases were operated within 6 days (range 0-6 days) after injury. The mean follow-up period was 2.8 years (range 2 3.5 years). The average duration of the external fixation was 1.6 months for fractures of the tibia, whereas it was 1.4 months for fractures of the femur. The average time for tibia fracture union was 2.8 months for fractures of the tibia, whereas it was 1.9 months for fractures of the femur. Malalignment in varus less than 5 degrees was noted in one patient. One patient had a limb-length discrepancy of 1.5 cms. There were five cases (18.5%) with pin-tract infection. According to the Association for the Study and Application of the Methods of Ilizarov evaluation system, bone results were excellent in 23 cases (85.2%), good in three cases (11.1%), and poor in one case (3.7%). Functional results were excellent in 22 (81.5%) cases and good in five (18.5%) cases. Combined use of external fixators and elastic intramedullary nails is a good method for the treatment of comminuted long bone fractures in children. PMID- 26999062 TI - Distal tibial derotational osteotomy with external fixation to treat torsional deformities: a review of 71 cases. AB - We retrospectively reviewed the safety and efficacy of operative treatment of torsional malalignment of the tibia in 44 children, on whom we performed 71 derotational osteotomies of the distal tibia to treat tibial torsion. We placed four pins using an alignment jig, performed a percutaneous osteotomy, and applied an external fixator after derotation. Postoperative radiographs showed accurate tibial derotation and pin placement in all patients. Nine patients developed superficial pin-tract infections that resolved with antibiotic treatment. Two developed fractures after removal of the external fixator, which healed in a plaster cast. Operative treatment of these cases with an external fixator is safe, effective, and well tolerated. PMID- 26999063 TI - Can the existing knowledge in depression treatment aid the recovery from the burnout syndrome? PMID- 26999065 TI - Information-based ranking of 10 compartment models of diffusion-weighted signal attenuation in fixed prostate tissue. AB - This study compares the theoretical information content of single- and multi compartment models of diffusion-weighted signal attenuation in prostate tissue. Diffusion-weighted imaging (DWI) was performed at 9.4 T with multiple diffusion times and an extended range of b values in four whole formalin-fixed prostates. Ten models, including different combinations of isotropic, anisotropic and restricted components, were tested. Models were ranked using the Akaike information criterion. In all four prostates, two-component models, comprising an anisotropic Gaussian component and an isotropic restricted component, ranked highest in the majority of voxels. Single-component models, whether isotropic (apparent diffusion coefficient, ADC) or anisotropic (diffusion tensor imaging, DTI), consistently ranked lower than multi-component models. Model ranking trends were independent of voxel size and maximum b value in the range tested (1.6-16 mm(3) and 3000-10,000 s/mm(2)). This study characterizes the two major water components previously identified by biexponential models and shows that models incorporating both anisotropic and restricted components provide more information rich descriptions of DWI signals in prostate tissue than single- or multi component anisotropic models and models that do not account for restricted diffusion. PMID- 26999064 TI - Promotion of In Vitro Chondrogenesis of Mesenchymal Stem Cells Using In Situ Hyaluronic Hydrogel Functionalized with Rod-Like Viral Nanoparticles. AB - This study focuses on the development of injectable hydrogels to mimic the cartilage microenvironment using hyaluronic acid (HA) derivatives as starting materials. Cysteine-inserted Tobacco mosaic virus (TMV) mutants (TMV1cys) could be cross-linked to methacrylated hyaluronic acid (MeHA) polymers by thiol-ene "click" chemistry and form hydrogels under physiological condition. The resulting hydrogels could promote in vitro chondrogenesis of bone marrow mesenchymal stem cells (BMSCs) significantly higher than that in the TMV-free HA hydrogels by upregulating bone morphogenetic protein-2 (BMP-2) expression and enhancing collagen accumulation. PMID- 26999066 TI - Do reading and spelling share a lexicon? AB - In the reading and spelling literature, an ongoing debate concerns whether reading and spelling share a single orthographic lexicon or rely upon independent lexica. Available evidence tends to support a single lexicon account over an independent lexica account, but evidence is mixed and open to alternative explanation. In the current work, we propose another, largely ignored account- separate-but-shared lexica--according to which reading and spelling have separate orthographic lexica, but information can be shared between them. We report three experiments designed to competitively evaluate these three theoretical accounts. In each experiment, participants learned new words via reading training and/or spelling training. The key manipulation concerned the amount of reading versus spelling practice a given item received. Following training, we assessed both response time and accuracy on final outcome measures of reading and spelling. According to the independent lexica account, final performance in one modality will not be influenced by the level of practice in the other modality. According to the single lexicon account, final performance will depend on the overall amount of practice regardless of modality. According to the separate-but-shared account, final performance will be influenced by the level of practice in both modalities but will benefit more from same-modality practice. Results support the separate-but-shared account, indicating that reading and spelling rely upon separate lexica, but information can be shared between them. PMID- 26999067 TI - An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor. AB - Human Aurora kinases, including Aurora kinase A (AURKA), B (AURKB), and C (AURKC), play an essential role in mitotic events such as monitoring of the mitotic checkpoint, creation of bipolar mitotic spindle and alignment of centrosomes on it, also regulating centrosome separation, bio-orientation of chromosomes and cytokinesis. AURKA and AURKB are key regulators of mitosis and centrosome via polymerizing microfilaments and controlling chromatid segregation. In particular, AURKA plays critical roles in the regulation of mitotic entry, centrosome function, bipolar spindle assembly, and chromosome segregation. AURKA has been found to be overexpressed in various solid and haematological cancers and has been linked with poor prognosis. Its important role in cancer initiation, growth, and metastasis has brought the focus to search for potent and selective AURKA inhibitors for cancer treatment. MLN8237, also known as alisertib, is one selective AURKA inhibitor that has shown remarkable anticancer effects in preclinical studies. Alisertib exhibits favourable pharmacokinetic properties. Alisertib has generally showed good partial response rates of 4-52% and good safety profiles in Phase I and II trials when it is solely administered as well as combined with cytotoxic chemotherapeutic drugs. Recently, the multicentre, randomized Phase III study of alisertib in patients with relapsed or refractory peripheral T-cell lymphoma has been discontinued due to unsatisfactory efficacy. The low risk of side effects, accessibility, and effectiveness of alisertib makes it a new promising anticancer therapy and further mechanistic and clinical studies are warranted. PMID- 26999068 TI - The role of Syk in cutaneous lupus erythematosus. PMID- 26999069 TI - MITF: More Interesting Traits, Folks! PMID- 26999070 TI - Microbiota-derived metabolites modulate tissue homeostasis: relevance to the oral cavity? PMID- 26999071 TI - The Optimal Dose of Hypofractionated Radiotherapy in Diffuse Intrinsic Pontine Glioma. PMID- 26999072 TI - Corrigendum: The Associations Between Maternal Factors During Pregnancy and the Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis. AB - Because of the erroneous application of multiple publications, the conclusions of our recent paper (Pediatr Blood Cancer 2015;62:1162-70) were not reliable. The corrected results show that coffee drinking during pregnancy was risk factor for childhood acute lymphoblastic leukemia (OR = 1.44, 95% confidence interval = 1.07 1.92). PMID- 26999073 TI - Temporal dynamics of arousal and attention in 12-month-old infants. AB - Research from the animal literature suggests that dynamic, ongoing changes in arousal lead to dynamic changes in an individual's state of anticipatory readiness, influencing how individuals distribute their attention to the environment. However, multiple peripheral indices exist for studying arousal in humans, each showing change on different temporal scales, challenging whether arousal is best characterized as a unitary or a heterogeneous construct. Here, in 53 typical 12-month-olds, we recorded heart rate (HR), head movement patterns, electrodermal activity (EDA), and attention (indexed via look duration) during the presentation of 20 min of mixed animations and TV clips. We also examined triggers for high arousal episodes. Using cross-correlations and auto correlations, we found that HR and head movement show strong covariance on a sub minute scale, with changes in head movement consistently preceding changes in HR. EDA showed significant covariance with both, but on much larger time-scales. HR and head movement showed consistent relationships with look duration, but the relationship is temporally specific: relations are observed between head movement, HR and look duration at 30 s time-lag, but not at larger time intervals. No comparable relationships were found for EDA. Changes in head movement and HR occurred before changes in look duration, but not for EDA. Our results suggest that consistent patterns of covariation between heart rate, head movement and EDA can be identified, albeit on different time-scales, and that associations with look duration are present for head movement and heart rate, but not for EDA. Our results suggests that there is a single construct of arousal that can identified across multiple measures, and that phasic changes in arousal precede phasic changes in look duration. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 623-639, 2016. PMID- 26999076 TI - Lower urinary tract symptoms in women: epidemiology, diagnosis, and management. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize and evaluate the most recent literature on the epidemiology, etiology, and treatment of lower urinary tract symptoms (LUTS) in women. RECENT FINDINGS: Several authors have studied characteristics of populations of women with LUTS and addressed care seeking behavior for these conditions. Multiple investigators also sought greater understanding of the urinary microbiome and its relationship to LUTS in women. Evidence for the treatment of overactive bladder and stress urinary incontinence is being synthesized and innovative treatments are being rigorously studied. SUMMARY: Investigations and high quality research continue to shed light on the epidemiology, diagnosis, and management of LUTS in women. PMID- 26999074 TI - Stimulation of dopamine D2-like receptors in the lumbosacral defaecation centre causes propulsive colorectal contractions in rats. AB - KEY POINTS: The pathophysiological roles of the CNS in bowel dysfunction in patients with irritable bowel syndrome and Parkinson's disease remain obscure. In the present study, we demonstrate that dopamine in the lumbosacral defaecation centre causes strong propulsive motility of the colorectum. The effect of dopamine is a result of activation of sacral parasympathetic preganglionic neurons via D2-like dopamine receptors. Considering that dopamine is a neurotransmitter of descending pain inhibitory pathways, our results highlight the novel concept that descending pain inhibitory pathways control not only pain, but also the defaecation reflex. In addition, severe constipation in patients with Parkinson's disease can be explained by reduced parasympathetic outflow as a result of a loss of the effect of dopaminergic neurons. ABSTRACT: We have recently demonstrated that intrathecally injected noradrenaline caused propulsive contractions of the colorectum. We hypothesized that descending pain inhibitory pathways control not only pain, but also the defaecation reflex. Because dopamine is one of the major neurotransmitters of descending pain inhibitory pathways in the spinal cord, we examined the effects of the intrathecal application of dopamine to the spinal defaecation centre on colorectal motility. Colorectal intraluminal pressure and expelled volume were recorded in vivo in anaesthetized rats. Slice patch clamp and immunohistochemistry were used to confirm the existence of dopamine-sensitive neurons in the sacral parasympathetic nuclei. Intrathecal application of dopamine into the L6-S1 spinal cord, where the lumbosacral defaecation centre is located, caused propulsive contractions of the colorectum. Inactivation of spinal neurons using TTX blocked the effect of dopamine. Although thoracic spinal transection had no effect on the enhancement of colorectal motility by intrathecal dopamine, the severing of the pelvic nerves abolished the enhanced motility. Pharmacological experiments revealed that the effect of dopamine is mediated primarily by D2-like dopamine receptors. Neurons labelled with retrograde dye injected at the colorectum showed an inward current in response to dopamine in slice patch clamp recordings. Furthermore, immunohistochemical analysis revealed that neurons immunoreactive to choline acetyltransferase express D2-like dopamine receptors. Taken together, our findings demonstrate that dopamine activates sacral parasympathetic preganglionic neurons via D2-like dopamine receptors and causes propulsive motility of the colorectum in rats. The present study supports the hypothesis that descending pain inhibitory pathways regulate defaecation reflexes. PMID- 26999075 TI - Mass Spectrometry Reveals Protein Kinase CK2 High-Order Oligomerization via the Circular and Linear Assembly. AB - CK2 is an intrinsically active protein kinase that is crucial for cellular viability. However, conventional kinase regulatory mechanisms do not apply to CK2, and its mode of regulation remains elusive. Interestingly, CK2 is known to undergo reversible ionic-strength-dependent oligomerization. Furthermore, a regulatory mechanism based on autoinhibitory oligomerization has been postulated on the basis of the observation of circular trimeric oligomers and linear CK2 assemblies in various crystal structures. Here, we employ native mass spectrometry to monitor the assembly of oligomeric CK2 species in an ionic strength-dependent manner. A subsequent combination of ion mobility spectrometry mass spectrometry and hydrogen-deuterium exchange mass spectrometry techniques was used to analyze the conformation of CK2 oligomers. Our findings support ionic strength-dependent CK2 oligomerization, demonstrate the transient nature of the alpha/beta interaction, and show that CK2 oligomerization proceeds via both the circular and linear assembly. PMID- 26999077 TI - Stereochemistry of N-Benzoyl-5-substituted-1-benzazepines Revisited: Synthesis of the Conformationally Biased Derivatives and Revision of the Reported Structure. AB - The syn (aR*,5R*) and anti (aS*,5R*) diastereomers of N-benzoyl-C5-substituted-1 benzazepines originating in the chiralities at C5 and the Ar-N(C?O) axis were first stereoselectively synthesized by biasing the conformation with a substituent at C6 and C9, respectively. Detailed examination of the stereochemistry (i.e., conformation and configuration) of these N-benzoyl-1 benzazepines by X-ray crystallographic analysis, VT NMR, and DFT calculations revealed new physicochemical aspects of these heterocycles including revision of the stereochemistry previously reported. PMID- 26999078 TI - Physiological and Cognitive Responses to an Antarctic Expedition: A Case Report. AB - PURPOSE: To assess changes in body composition and monitor cognitive function, subjective well-being, and physiological stress, as measured by salivary hormones and markers of mucosal immunity, during an Antarctic expedition. METHODS: A 36-y old man (188.2 cm height, 94.5 kg body mass) took part in a world-record attempt. A total-body dual-energy X-ray absorptiometry scan and measurement of 8 skinfolds and 5 girths were performed before and after the expedition. In addition, daily subjective data were recorded (sleep quality, total hours of sleep, energy levels, perceived exertion, mood, muscle soreness, and muscle/joint pain) along with distance covered and hours of physical activity per day. As a measure of cognitive function, the athlete completed a computerized battery of tasks (Axon Sports Cognitive Priming Application) every third morning. Saliva samples were collected before, during, and after the expedition to determine salivary cortisol (sCort), testosterone (sT), alpha amylase (sAA), and secretory immunoglobulin A (sIgA). RESULTS: The athlete lost 5.3 kg body mass and sum of 8 skinfolds decreased from 73 mm to 59 mm from preexpedition to postexpedition. Psychomotor speed declined over the course of the expedition. sT increased and sCort decreased throughout, and sAA and sIgA peaked toward the end of the expedition. CONCLUSIONS: This case study provides novel data about the physiological and cognitive impact of an Antarctic expedition. The findings may inform strategies for future expeditions, allowing individuals undertaking expeditions of this nature to better prepare for success. PMID- 26999080 TI - Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1. AB - A new CYP26A1 homology model was built based on the crystal structure of cyanobacterial CYP120A1. The model quality was examined for stereochemical accuracy, folding reliability, and absolute quality using a variety of different bioinformatics tools. Furthermore, the docking capabilities of the model were assessed by docking of the natural substrate all-trans-retinoic acid (atRA), and a group of known azole- and tetralone-based CYP26A1 inhibitors. The preferred binding pose of atRA suggests the (4S)-OH-atRA metabolite production, in agreement with recently available experimental data. The distances between the ligands and the heme group iron of the enzyme are in agreement with corresponding distances obtained for substrates and azole inhibitors for other cytochrome systems. The calculated theoretical binding energies agree with recently reported experimental data and show that the model is capable of discriminating between natural substrate, strong inhibitors (R116010 and R115866), and weak inhibitors (liarozole, fluconazole, tetralone derivatives). PMID- 26999079 TI - Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations. AB - A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to the Distributed Drug Discovery (D3) project. Using a BAL-based solid-phase synthetic sequence the proline or proline homologue subunit is both constructed and incorporated into the peptidomimetic by an alpha-alkylation, hydrolysis and intramolecular cyclization sequence. Further transformations on solid-phase provide access to a variety of piperazine derivatives representing a class of molecules known to exhibit central nervous system activity. The procedure works well with proline cores, but with larger six- and seven-membered ring homologues the nature of the carboxylic acid acylating the cyclic amine can lead to side reactions and result in poor overall yields. PMID- 26999081 TI - Self-Assembled Modified Soy Protein/Dextran Nanogel Induced by Ultrasonication as a Delivery Vehicle for Riboflavin. AB - A simple and green approach was developed to produce a novel nanogel via self assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 degrees C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and zeta potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM) revealed the NGs to be spherical with core-shell structures, in the range of 32-40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 MUg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF) compared with simulated gastric fluid (SGF). From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes. PMID- 26999082 TI - Experimental Investigation and Simplistic Geochemical Modeling of CO2 Mineral Carbonation Using the Mount Tawai Peridotite. AB - In this work, the potential of CO2 mineral carbonation of brucite (Mg(OH)2) derived from the Mount Tawai peridotite (forsterite based (Mg)2SiO4) to produce thermodynamically stable magnesium carbonate (MgCO3) was evaluated. The effect of three main factors (reaction temperature, particle size, and water vapor) were investigated in a sequence of experiments consisting of aqueous acid leaching, evaporation to dryness of the slurry mass, and then gas-solid carbonation under pressurized CO2. The maximum amount of Mg converted to MgCO3 is ~99%, which occurred at temperatures between 150 and 175 degrees C. It was also found that the reduction of particle size range from >200 to <75 um enhanced the leaching rate significantly. In addition, the results showed the essential role of water vapor in promoting effective carbonation. By increasing water vapor concentration from 5 to 10 vol %, the mineral carbonation rate increased by 30%. This work has also numerically modeled the process by which CO2 gas may be sequestered, by reaction with forsterite in the presence of moisture. In both experimental analysis and geochemical modeling, the results showed that the reaction is favored and of high yield; going almost to completion (within about one year) with the bulk of the carbon partitioning into magnesite and that very little remains in solution. PMID- 26999083 TI - Molecular Cloning of cpcU and Heterodimeric Bilin Lyase Activity Analysis of CpcU and CpcS for Attachment of Phycocyanobilin to Cys-82 on the beta-Subunit of Phycocyanin in Arthrospira platensis FACHB314. AB - A new bilin lyase gene cpcU was cloned from Arthrospira platensis FACHB314 to study the assembly of the phycocyanin beta-Subunit. Two recombinant plasmids, one contained the phycocyanobilin (PCB) producing genes (hoxI and pcyA), while the other contained the gene of the beta-Subunit of phycobiliprotein (cpcB) and the lyase gene (cpcU, cpcS, or cpcU/S) were constructed and separately transferred into Escherichia coli in order to test the activities of relevant lyases for catalyzing PCB addition to CpcB during synthesizing fluorescent beta-PC of A. platensis FACHB314. The fluorescence intensity examination showed that Cys-82 maybe the active site for the beta-Subunit binding to PCBs and the attachment could be carried out by CpcU, CpcS, or co-expressed cpcU/S in A. platensis FACHB314. PMID- 26999084 TI - Fumigant Toxicity of Lamiaceae Plant Essential Oils and Blends of Their Constituents against Adult Rice Weevil Sitophilus oryzae. AB - To find a new and safe alternative to conventional insecticides, we evaluated the fumigant toxicity of eight Lamiaceae essential oils and their constituents against the adult rice weevil Sitophilus oryzae. Of the eight species tested, hyssop (Hyssopus offcinalis), majoram (Origanum majorana), and Thymus zygis essential oils showed strong fumigant toxicity against S. oryzae adults at 25 mg/L air concentration. Constituents of active essential oils were analyzed by gas chromatography coupled to flame ionization detector (FID) and gas chromatography-mass spectrometry. A total of 13, 15, and 17 compounds were identified from hyssop, majoram, and Thymus zygis essential oils, respectively. Pinocamphone and isopinocamphone were isolated by open column chromatography. Among the test compounds, pinocamphone and isopinocamphone showed the strongest fumigant toxicity against S. oryzae. Sabinene hydrate, linalool, alpha-terpineol, and terpinen-4-ol exhibited 100% fumigant toxicity against S. oryzae at 3.9 mg/L air concentration. The measured toxicity of the artificial blends of the constituents identified in hyssop, majoram, and Thymus zygis oils indicated that isopinocamphone, terpine-4-ol, and linalool were major contributors to the fumigant toxicity of the artificial blend, respectively. PMID- 26999085 TI - Azidation in the Difunctionalization of Olefins. AB - Organic azides are key motifs in compounds of relevance to chemical biology, medicinal chemistry and materials science. In addition, they also serve as useful building blocks due to their remarkable reactivity. Therefore, the development of efficient protocols to synthesize these compounds is of great significance. This paper reviews the major applications and development of azidation in difunctionalization of olefins using azide reagents. PMID- 26999087 TI - Aromatic Constituents from the Stems of Astragalus membranaceus (Fisch.) Bge. var. Mongholicus (Bge.) Hsiao. AB - Four new aromatic constituents, astraflavonoids A (1), B (2), C (3), and astramemoside A (4), along with sixteen known ones 5-20 were obtained from the stems of A. membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. Their structures were elucidated by chemical and spectroscopic methods. Among the known isolates, 14 was obtained from the Astragalus genus for the first time, while 7 12, 18-20 were isolated from the species for the first time. The effects of the compounds obtained from the plant on glucose consumption were analyzed in differentiated L6 myotubes in vitro, whereby compounds 1, 2, 3, 7, 8, 10, 11, 14, 15 and 18 displayed significant promoting effects on glucose consumption in L6 myotubes. Among them, the activities of 1, 2 and 7 were comparable to that of insulin, which suggested that these compounds may be involved in glucose metabolism and transport. PMID- 26999086 TI - A New Indole Alkaloid from the Toad Venom of Bufo bufo gargarizans. AB - A new indole alkaloid named bufobutarginine (1), along with three known bufotenines, namely, serotonin (2), bufotenidine (3), and bufotenine (4), were isolated from the water extract of toad venom. Their structures were elucidated by spectral methods. This is the first time that arginine has been found to be involved in the biosynthesis of bufotenines in parotid of toad. The cytotoxic activities of these compounds have been assayed against A375 and A549 cell lines by the MTT method; however, they showed no cytotoxic activities. PMID- 26999088 TI - Flavonoids, Antioxidant Potential, and Acetylcholinesterase Inhibition Activity of the Extracts from the Gametophyte and Archegoniophore of Marchantia polymorpha L. AB - Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte of M. polymorpha L. have been reported. However, as the reproductive organ of M. polymorpha L., the bioactivity and flavonoids profile of the archegoniophore have not been reported, so in this work the flavonoid profiles, antioxidant and acetylcholinesterase inhibition activities of the extracts from the archegoniophore and gametophyte of M. polymorpha L. were compared by radical scavenging assay methods (DPPH, ABTS, O(2-)), reducing power assay, acetylcholinesterase inhibition assay and LC-MS analysis. The results showed that the total flavonoids content in the archegoniophore was about 10-time higher than that of the gametophyte. Differences between the archegoniophore and gametophyte of M. polymorpha L. were observed by LC-MS analysis. The archegoniophore extracts showed stronger bio-activities than those of the gametophyte. The archegoniophore extract showed a significant acetylcholinesterase inhibition, while the gametophyte extract hardly inhibited it. PMID- 26999089 TI - New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy. AB - Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases. PMID- 26999090 TI - Fluoride-Promoted Esterification (FPE) Chemistry: A Robust Route to Bis-MPA Dendrons and Their Postfunctionalization. AB - Bifunctional dendrons based on 2,2-bis(methylol)propionic acid (bis-MPA) are highly desirable scaffolds for biomedical applications. This is due to their flawless nature and large and exact number of functional groups as well as being biodegradable and biocompatible. Herein, we describe a facile divergent growth approach to their synthesis from monobenzylated tetraethylene glycol and post functionalization utilizing fluoride-promoted esterification (FPE) chemistry protocols. The scaffolds, presenting selectively deprotectable hydroxyls in the periphery and at the focal point, were isolated on a multigram scale with excellent purity up to the fourth generation dendron with a molecular weight of 2346 Da in seven reactions with a total yield of 50%. The third generation dendron was used as a model compound to demonstrate its functionalizability. Selective deprotection of the dendron's focal point was achieved with an outstanding yield of 94%, and biotin as well as azido functionalities were introduced to its focal point and periphery, respectively, through FPE chemistry. Bulky disperse red dyes were clicked through CuAAC to the dendron's azido groups, giving a biotinylated dendron with multivalent dyes with a molecular weight of 6252 Da in a total yield of 37% in five reactions with an average yield of 82% starting from the third generation focally and peripherally protected dendron. FPE chemistry proved to be a superb improvement over previous protocols towards bis-MPA dendrons as high purity and yields were obtained with less toxic solvents and greatly improved monomer utilization. PMID- 26999091 TI - Searching for Multi-Targeting Neurotherapeutics against Alzheimer's: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif. AB - The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer's disease (AD), shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors through the decoration of the 2H chromen-2-one skeleton. Compounds bearing a propargylamine moiety at position 3 displayed the highest in vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC50 = 8.99 uM) and a potent and selective MAO-B inhibitor (IC50 = 2.8 nM). Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 uM) under oxidative stress conditions promoted by two mitochondrial toxins (oligomycin-A and rotenone). In a Madin Darby canine kidney (MDCK)II-MDR1 cell-based transport study, Compound 3h was able to permeate the BBB-mimicking monolayer and did not result in a glycoprotein p (P-gp) substrate, showing an efflux ratio = 0.96, close to that of diazepam. PMID- 26999092 TI - Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine. AB - The biological activity of nanosize silver particles towards oral epithelium derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle's medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 MUg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm +/- 4 nm was measured by 3 (4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 MUg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50) after 48 h was estimated at 5.19 MUg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti cancer drugs. PMID- 26999093 TI - Binding Mode and Selectivity of Steroids towards Glucose-6-phosphate Dehydrogenase from the Pathogen Trypanosoma cruzi. AB - Glucose-6-phosphate dehydrogenase (G6PDH) plays a housekeeping role in cell metabolism by generating reducing power (NADPH) and fueling the production of nucleotide precursors (ribose-5-phosphate). Based on its indispensability for pathogenic parasites from the genus Trypanosoma, G6PDH is considered a drug target candidate. Several steroid-like scaffolds were previously reported to target the activity of G6PDH. Epiandrosterone (EA) is an uncompetitive inhibitor of trypanosomal G6PDH for which its binding site to the enzyme remains unknown. Molecular simulation studies with the structure of Trypanosoma cruzi G6PDH revealed that EA binds in a pocket close to the G6P binding-site and protrudes into the active site blocking the interaction between substrates and hence catalysis. Site directed mutagenesis revealed the important steroid-stabilizing effect of residues (L80, K83 and K84) located on helix alpha-1 of T. cruzi G6PDH. The higher affinity and potency of 16alpha-Br EA by T. cruzi G6PDH is explained by the formation of a halogen bond with the hydrogen from the terminal amide of the NADP+-nicotinamide. At variance with the human enzyme, the inclusion of a 21 hydroxypregnane-20-one moiety to a 3beta-substituted steroid is detrimental for T. cruzi G6PDH inhibition. The species-specificity of certain steroid derivatives towards the parasite G6PDH and the corresponding biochemically validated binding models disclosed in this work may prove valuable for the development of selective inhibitors against the pathogen's enzyme. PMID- 26999094 TI - Pharmacokinetics of Maleic Acid as a Food Adulterant Determined by Microdialysis in Rat Blood and Kidney Cortex. AB - Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively). The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC) of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively), indicating that greater accumulation of maleic acid occurred in the rat kidney. PMID- 26999095 TI - Comparison of the Profile and Composition of Volatiles in Coniferous Needles According to Extraction Methods. AB - The enantiomeric distribution and profile of volatiles in plants, which affect the biological and organoleptic properties, can be varied depending on extraction methods as well as their cultivars. The secondary volatile components of the needles of three conifer cultivars (Chamaecyparispisifera, Chamaecyparisobtusa, and Thujaorientalis) were compared. Furthermore, the effects of three different extraction methods--solid-phase microextraction (SPME), steam distillation (SD), and solvent extraction (SE)--on the composition and enantiomeric distribution of those volatiles were elucidated. Monoterpene hydrocarbons predominated in all samples, and the compositions of sesquiterpenes and diterpenes differed according to the cultivar. In particular, the yields of oxygenated monoterpenes and sesquiterpenes were greatest for SD, whereas those of sesquiterpenes and diterpenes were highest for SE. On the other hand, more monoterpenes with higher volatility could be obtained with SPME and SD than when using SE. In addition, the enantiomeric composition of nine chiral compounds found in three cultivars differed according to their chemotype. There were also some differences in the yielded oxygenated monoterpenes and sesquiterpene hydrocarbons, but not monoterpene hydrocarbons, according to the extraction method. These results demonstrate that the extraction methods used as well as the cultivars influence the measured volatile profiles and enantiomeric distribution of coniferous needle extracts. PMID- 26999096 TI - Proteomic Profiling of Iron Overload-Induced Human Hepatic Cells Reveals Activation of TLR2-Mediated Inflammatory Response. AB - BACKGROUND: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. METHODS AND RESULTS: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC) to establish an in vitro iron overload model. Differentially expressed proteins initiated by the iron overload were studied by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS) analysis. We identified 93 proteins whose quantity statistically significantly changes under excess hepatocyte iron conditions. Gene Ontology (GO) analysis showed that these differentially expressed proteins in HH4 cells are involved in various biological process including endocytosis, response to wounding, di-, trivalent inorganic cation homeostasis, inflammatory response, positive regulation of cytokine production, and etc. Meanwhile, proteomics data revealed protein level of TLR2 and IL6ST significantly increased 7 times and 2.9 times, respectively, in iron overloaded HH4 cells. Our subsequent experiments detected that FAC-treated HH4 cells can activate IL6 expression through TLR2-mediated inflammatory responses via the NF-kappaB pathway. CONCLUSIONS: In this study, we demonstrated that iron overload induced hepatocytes triggering TLR2-mediated inflammatory response via NF-kappaB signaling pathway in HH4 cells. PMID- 26999097 TI - Synthesis of Fluorinated Polymers and Evaluation of Wettability. AB - Two kinds of fluorinated polymers were synthesized: an acrylate polymer having a fluorinated triethylene glycol as a pendant group (2a) and a fluoroalkyl acrylate polymer (2b). The contact angle of these fluorinated polymers against water, non fluorinated alcohols and fluorinated alcohols were evaluated. As compared with the fluoroalkyl polymer (2b), fluoroethylene glycol polymer (2a) showed smaller contact angle against water and non-fluorinated alcohols. This supports the proposition that changing the alkyl chain into the ethylene glycol-type chain gave some interaction between etheric oxygen and water or non-fluorinated alcohols. In addition, fluoroalkyl acrylate polymer (2b) showed remarkably low values of critical surface tension. PMID- 26999098 TI - Production of Fusaric Acid by Fusarium spp. in Pure Culture and in Solid Medium Co-Cultures. AB - The ability of fungi isolated from nails of patients suffering from onychomycosis to induce de novo production of bioactive compounds in co-culture was examined. Comparison between the metabolite profiles produced by Sarocladium strictum, by Fusarium oxysporum, and by these two species in co-culture revealed de novo induction of fusaric acid based on HRMS. Structure confirmation of this toxin, using sensitive microflow NMR, required only three 9-cm Petri dishes of fungal culture. A targeted metabolomics study based on UHPLC-HRMS confirmed that the production of fusaric acid was strain-dependent. Furthermore, the detected toxin levels suggested that onychomycosis-associated fungal strains of the F. oxysporum and F. fujikuroi species complexes are much more frequently producing fusaric acid, and in higher amount, than strains of the F. solani species complex. Fusarium strains producing no significant amounts of this compound in pure culture, were shown to de novo produce that compound when grown in co-culture. The role of fusaric acid in fungal virulence and defense is discussed. PMID- 26999099 TI - Coenzyme Q and Its Role in the Dietary Therapy against Aging. AB - Coenzyme Q (CoQ) is a naturally occurring molecule located in the hydrophobic domain of the phospholipid bilayer of all biological membranes. Shortly after being discovered, it was recognized as an essential electron transport chain component in mitochondria where it is particularly abundant. Since then, more additional roles in cell physiology have been reported, including antioxidant, signaling, death prevention, and others. It is known that all cells are able to synthesize functionally sufficient amounts of CoQ under normal physiological conditions. However, CoQ is a molecule found in different dietary sources, which can be taken up and incorporated into biological membranes. It is known that mitochondria have a close relationship with the aging process. Additionally, delaying the aging process through diet has aroused the interest of scientists for many years. These observations have stimulated investigation of the anti aging potential of CoQ and its possible use in dietary therapies to alleviate the effects of aging. In this context, the present review focus on the current knowledge and evidence the roles of CoQ cells, its relationship with aging, and possible implications of dietary CoQ in relation to aging, lifespan or age related diseases. PMID- 26999100 TI - Functionalization of Calcium Sulfate/Bioglass Scaffolds with Zinc Oxide Whisker. AB - There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that the scaffolds presented a strong antibacterial activity after introducing ZnOw, due to the antibacterial factors released from the degradation of ZnO. Moreover, ZnOw was also found to have a distinct reinforcing effect on mechanical properties. This was ascribed to whisker pull-out, crack bridging, crack deflection, crack branching and other toughening mechanisms. In addition, the cell culture experiments showed that the scaffolds with ZnOw had a good biocompatibility. PMID- 26999101 TI - Compound Library Screening Identified Cardiac Glycoside Digitoxin as an Effective Growth Inhibitor of Gefitinib-Resistant Non-Small Cell Lung Cancer via Downregulation of alpha-Tubulin and Inhibition of Microtubule Formation. AB - Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 MUM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing alpha-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest. PMID- 26999102 TI - A Novel Biomolecule-Mediated Reduction of Graphene Oxide: A Multifunctional Anti Cancer Agent. AB - Graphene oxide (GO) is a monolayer of carbon atoms that form a dense honeycomb structure, consisting of hydroxyl and epoxide functional groups on the two accessible sides and carboxylic groups at the edges. In contrast, graphene is a two-dimensional sheet of sp2-hybridized carbon atoms packed into a honeycomb lattice. Graphene has great potential for use in biomedical applications due to its excellent physical and chemical properties. In this study, we report a facile and environmentally friendly approach for the synthesis of reduced graphene oxide (rGO) using uric acid (UA). The synthesized uric acid-reduced graphene oxide (UA rGO) was fully characterized by ultraviolet-visible (UV-Vis) absorption spectra, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and Raman spectroscopy. GO and UA-rGO induced a dose-dependent decrease in cell viability and induced cytotoxicity in human ovarian cancer cells. The results from this study suggest that UA-rGO could cause apoptosis in mammalian cells. The toxicity of UA-rGO is significantly higher than GO. Based on our findings, UA-rGO shows cytotoxic effects against human ovarian cancer cells, and its synthesis is environmentally friendly. UA-rGO significantly inhibits cell viability by increasing lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, activation of caspase-3, and DNA fragmentation. This is the first report to describe the comprehensive effects of UA-rGO in ovarian cancer cells. We believe that the functional aspects of newly synthesized UA-rGO will provide advances towards various biomedical applications in the near future. PMID- 26999103 TI - Development and Characterization of Novel Microsatellite Markers for the Peach Fruit Moth Carposina sasakii (Lepidoptera: Carposinidae) Using Next-Generation Sequencing. AB - The peach fruit moth Carposina sasakii is an economically important pest on dozens of fruits from Rosaceae and Rhamnaceae in Northeast Asia. We developed novel microsatellite markers for C. sasakii from randomly sequenced regions of the genome using next-generation sequencing. In total, 95,153 microsatellite markers were isolated from 4.70 GB genomic sequences. Thirty-five polymorphic markers were developed by assessing in 63 individuals from two geographical populations. The allele numbers ranged from 2 to 9 with an average value of 4.60 per locus, while the polymorphism information content ranged from 0.075 to 0.696 with an average value of 0.407. Furthermore, the observed and expected heterozygosity varied from 0.000 to 0.677 and 0.062 to 0.771, respectively. The microsatellites developed provide abundant molecular markers for investigating genetic structure, genetic diversity, and existence of host-plant associated biotypes of C. sasakii. PMID- 26999104 TI - Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Application of Metabolomics. AB - Gut microbiota are intricately involved in the development of obesity-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance. In the current review, we discuss the role of gut microbiota in the development of NAFLD by focusing on the mechanisms of gut microbiota-mediated host energy metabolism, insulin resistance, regulation of bile acids and choline metabolism, as well as gut microbiota-targeted therapy. We also discuss the application of a metabolomic approach to characterize gut microbial metabotypes in NAFLD. PMID- 26999106 TI - Molecular Neurobiology and Promising New Treatment in Depression. AB - The limited effects of currently available antidepressants are becoming an urgent issue in depression research. It takes a long time to determine treatment effects, and the overall remission rate is low. Although we expect the development of non-monoamine antidepressants in the near future, efforts in this regard over the past several decades have not yet been compensated. Thus, researchers and clinicians should clarify the neurobiological mechanisms of integrated modulators that regulate changes in genes, cells, the brain, and behaviors associated with depression. In this study, we review molecular neurobiological theories and new treatments for depression. Beyond neuroanatomy and monoamine theory, we discuss cells and molecules, neural plasticity, neurotrophisms, endocrine mechanisms, immunological mechanisms, genetics, circadian rhythms, and metabolic regulation in depression. In addition, we introduce the possibility of new antidepressant drug development using protein translation signaling (mTOR) pathways. PMID- 26999105 TI - Mitochondrial Molecular Pathophysiology of Nonalcoholic Fatty Liver Disease: A Proteomics Approach. AB - Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that can progress to nonalcoholic steatohepatitis, cirrhosis and cancer. It is considered an emerging health problem due to malnourishment or a high-fat diet (HFD) intake, which is observed worldwide. It is well known that the hepatocytes' apoptosis phenomenon is one of the most important features of NAFLD. Thus, this review focuses on revealing, through a proteomics approach, the complex network of protein interactions that promote fibrosis, liver cell stress, and apoptosis. According to different types of in vitro and murine models, it has been found that oxidative/nitrative protein stress leads to mitochondrial dysfunction, which plays a major role in stimulating NAFLD damage. Human studies have revealed the importance of novel biomarkers, such as retinol-binding protein 4, lumican, transgelin 2 and hemoglobin, which have a significant role in the disease. The post-genome era has brought proteomics technology, which allows the determination of molecular pathogenesis in NAFLD. This has led to the search for biomarkers which improve early diagnosis and optimal treatment and which may effectively prevent fatal consequences such as cirrhosis or cancer. PMID- 26999107 TI - Telomeres, NAFLD and Chronic Liver Disease. AB - Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease. PMID- 26999108 TI - Overexpression of G0/G1 Switch Gene 2 in Adipose Tissue of Transgenic Quail Inhibits Lipolysis Associated with Egg Laying. AB - In avians, yolk synthesis is regulated by incorporation of portomicrons from the diet, transport of lipoproteins from the liver, and release of lipids from adipose tissue; however, the extent to which lipolysis in adipose tissue contributes to yolk synthesis and egg production has yet to be elucidated. G0/G1 switch gene 2 (G0S2) is known to bind and inhibit adipose triglyceride lipase (ATGL), the rate-limiting enzyme in lipolysis. The objective of this study was to determine whether overexpression of the G0S2 gene in adipose tissue could successfully inhibit endogenous ATGL activity associated with egg laying. Two independent lines of transgenic quail overexpressing G0S2 had delayed onset of egg production and reduced number of eggs over a six-week period compared to non transgenic quail. Although no differences in measured parameters were observed at the pre-laying stage (5 weeks of age), G0S2 transgenic quail had significantly larger interclavicular fat pad weights and adipocyte sizes and lower NEFA concentrations in the serum at early (1 week after laying first egg) and active laying (5 weeks after laying first egg) stages. Overexpression of G0S2 inhibited lipolysis during early and active laying, which drastically shifted the balance towards a net accumulation of triacylglycerols and increased adipose tissue mass. Thereby, egg production was negatively affected as less triacylglycerols were catabolized to produce lipids for the yolk. PMID- 26999109 TI - Expression and Sequence Variants of Inflammatory Genes; Effects on Plasma Inflammation Biomarkers Following a 6-Week Supplementation with Fish Oil. AB - (1) BACKGROUND: A growing body of literature suggest that polymorphisms (SNPs) from inflammation-related genes could possibly play a role in cytokine production and then interact with dietary n-3 fatty acids (FAs) to modulate inflammation. The aim of the present study was to test whether gene expression of selected inflammatory genes was altered following an n-3 PUFA supplementation and to test for gene-diet interactions modulating plasma inflammatory biomarker levels. (2) METHODS: 191 subjects completed a 6-week n-3 FA supplementation with 5 g/day of fish oil. Gene expression of TNF-alpha and IL6 was assessed in peripheral blood mononuclear cells (PBMCs) using the TaqMan technology. Genotyping of 20 SNPs from the TNF-LTA gene cluster, IL1beta, IL6 and CRP genes was performed. (3) RESULTS: There was no significant reduction of plasma IL-6, TNF-alpha and C-reactive protein (CRP) levels after the 6-week fish oil supplementation. TNF-alpha and IL6 were slightly overexpressed in PBMCs after the supplementation (fold changes of 1.05 +/- 0.38 and 1.18 +/- 0.49, respectively (n = 191)), but relative quantification (RQ) within the -0.5 to 2.0 fold are considered as nonbiologically significant. In a MIXED model for repeated measures adjusted for the effects of age, sex and BMI, gene by supplementation interaction effects were observed for rs1143627, rs16944, rs1800797, and rs2069840 on IL6 levels, for rs2229094 on TNF alpha levels and for rs1800629 on CRP levels (p < 0.05 for all). (4) CONCLUSIONS: This study shows that a 6-week n-3 FA supplementation with 5 g/day of fish oil did not alter gene expression levels of TNF-alpha and IL6 in PBMCs and did not have an impact on inflammatory biomarker levels. However, gene-diet interactions were observed between SNPs within inflammation-related genes modulating plasma inflammatory biomarker levels. PMID- 26999110 TI - De novo Transcriptome Generation and Annotation for Two Korean Endemic Land Snails, Aegista chejuensis and Aegista quelpartensis, Using Illumina Paired-End Sequencing Technology. AB - Aegista chejuensis and Aegista quelpartensis (Family-Bradybaenidae) are endemic to Korea, and are considered vulnerable due to declines in their population. The limited genetic resources for these species restricts the ability to prioritize conservation efforts. We sequenced the transcriptomes of these species using Illumina paired-end technology. Approximately 257 and 240 million reads were obtained and assembled into 198,531 and 230,497 unigenes for A. chejuensis and A. quelpartensis, respectively. The average and N50 unigene lengths were 735.4 and 1073 bp, respectively, for A. chejuensis, and 705.6 and 1001 bp, respectively, for A. quelpartensis. In total, 68,484 (34.5%) and 77,745 (33.73%) unigenes for A. chejuensis and A. quelpartensis, respectively, were annotated to databases. Gene Ontology terms were assigned to 23,778 (11.98%) and 26,396 (11.45) unigenes, for A. chejuensis and A. quelpartensis, respectively, while 5050 and 5838 unigenes were mapped to 117 and 124 pathways in the Kyoto Encyclopedia of Genes and Genomes database. In addition, we identified and annotated 9542 and 10,395 putative simple sequence repeats (SSRs) in unigenes from A. chejuensis and A. quelpartensis, respectively. We designed a list of PCR primers flanking the putative SSR regions. These microsatellites may be utilized for future phylogenetics and conservation initiatives. PMID- 26999111 TI - Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening. AB - Endothelin-1 receptors (ETAR and ETBR) act as a pivotal regulator in the biological effects of ET-1 and represent a potential drug target for the treatment of multiple cardiovascular diseases. The purpose of the study is to discover dual ETA/ETB receptor antagonists from traditional Chinese herbs. Ligand and structure-based virtual screening was performed to screen an in-house database of traditional Chinese herbs, followed by a series of in vitro bioassay evaluation. Aristolochic acid A (AAA) was first confirmed to be a dual ETA/ETB receptor antagonist based intracellular calcium influx assay and impedance-based assay. Dose-response curves showed that AAA can block both ETAR and ETBR with IC50 of 7.91 and 7.40 MUM, respectively. Target specificity and cytotoxicity bioassay proved that AAA is a selective dual ETA/ETB receptor antagonist and has no significant cytotoxicity on HEK293/ETAR and HEK293/ETBR cells within 24 h. It is a feasible and effective approach to discover bioactive compounds from traditional Chinese herbs using in silico screening combined with in vitro bioassay evaluation. The structural characteristic of AAA for its activity was especially interpreted, which could provide valuable reference for the further structural modification of AAA. PMID- 26999112 TI - Ionogels Based on Poly(methyl methacrylate) and Metal-Containing Ionic Liquids: Correlation between Structure and Mechanical and Electrical Properties. AB - Ionogels (IGs) based on poly(methyl methacrylate) (PMMA) and the metal-containing ionic liquids (ILs) bis-1-butyl-3-methlimidazolium tetrachloridocuprate(II), tetrachloride cobaltate(II), and tetrachlorido manganate(II) have been synthesized and their mechanical and electrical properties have been correlated with their microstructure. Unlike many previous examples, the current IGs show a decreasing stability in stress-strain experiments on increasing IL fractions. The conductivities of the current IGs are lower than those observed in similar examples in the literature. Both effects are caused by a two-phase structure with micrometer-sized IL-rich domains homogeneously dispersed an IL-deficient continuous PMMA phase. This study demonstrates that the IL-polymer miscibility and the morphology of the IGs are key parameters to control the (macroscopic) properties of IGs. PMID- 26999114 TI - Phenolic Profile and Biological Activities of the Pepino (Solanum muricatum) Fruit and Its Wild Relative S. caripense. AB - The pepino (Solanum muricatum) is an edible and juicy fruit native to the Andean region which is becoming increasingly important. However, little information is available on its phenolic composition and bioactive properties. Four pepino varieties (37-A, El Camino, Puzol, and Valencia) and one accession (E-7) of its close wild relative S. caripense were characterized by HPLC-DAD-MS(n)/ESI. Twenty four hydroxycinnamic acid derivatives were detected (5 to 16 compounds per variety or accession), with differences of more than two-fold for their total content among the materials studied. The major phenolics in the pepino varieties were chlorogenic acids and derivatives, while in S. caripense a caffeoyl-synapoyl quinic acid was the major compound. The in vitro antioxidant capacity (DPPH (2,2 diphenyl-1-picrylhydrazyl hydrate), ORAC (oxygen radical absorbance capacity), and TRC (total reducing capacity) tests) was higher in S. caripense. Pepino and S. caripense extracts were not toxic for RAW 264.7 macrophage cells, and the raw extracts inhibited NO production of the lipopolysaccharide (LPS)-stimulated macrophages by 36% (El Camino) to 67% (37-A). No single variety ranked high simultaneously for hydroxycinnamic acids content, antioxidant activity and biological activity. We suggest the screening of large collections of germplasm or the use of complementary crosses between Puzol (high for hydroxycinnamic acids and biological activity) and S. caripense E-7 (high for antioxidant activity) to select and breed pepino varieties with enhanced properties. PMID- 26999113 TI - Long-Term Treatment with Citicoline Prevents Cognitive Decline and Predicts a Better Quality of Life after a First Ischemic Stroke. AB - Stroke, as the leading cause of physical disability and cognitive impairment, has a very significant impact on patients' quality of life (QoL). The objective of this study is to know the effect of citicoline treatment in Qol and cognitive performance in the long-term in patients with a first ischemic stroke. This is an open-label, randomized, parallel study of citicoline vs. usual treatment. All subjects were selected 6 weeks after suffering a first ischemic stroke and randomized into parallel arms. Neuropsychological evaluation was performed at 1 month, 6 months, 1 year and 2 years after stroke, and QoL was measured using the EuroQoL-5D questionnaire at 2 years. 163 patients were followed during 2 years. The mean age was 67.5 years-old, and 50.9% were women. Age and absence of citicoline treatment were independent predictors of both utility and poor quality of life. Patients with cognitive impairment had a poorer QoL at 2 years (0.55 vs. 0.66 in utility, p = 0.015). Citicoline treatment improved significantly cognitive status during follow-up (p = 0.005). In conclusion, treatment with long term citicoline is associated with a better QoL and improves cognitive status 2 years after a first ischemic stroke. PMID- 26999115 TI - Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan. AB - Taiwan has been recognized by the World Organization for Animal Health as rabies free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 * 10(-4)-4.75 * 10(-4) substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers. PMID- 26999116 TI - Influence of Long-Distance Bicycle Riding on Serum/Urinary Biomarkers of Prostate Cancer. AB - Herein, we present a study focused on the determination of the influence of long distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49-57 years with a median of 52 years, underwent physical exercise (mean race time of 150 +/- 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 umol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0-0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 umol/mL for serum sarcosine, and p = 0.15, median 0.02 umol/mmol of creatinine vs. 0.01 umol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa-sarcosine does not have a drawback by means of a bicycle riding induced false positivity, as was shown in the case of PSA. PMID- 26999117 TI - Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population. AB - Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs) on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease) in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI) and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, chi2 = 4.6, odds ratio (OD) = 1.5; rs4977574 p = 0.0336, chi2 = 4.5, OD = 1.4; rs2891168 p = 1.85 * 10 - 10, chi2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 * 10 - 9, chi2 = 34.1, OD = 2.2). The study identified three protective haplotypes (TAAG p = 1.00 * 10 - 4; AGTA p = 0.022 and GGGCC p = 0.0175) and a risk haplotype (TGGA p = 2.86 * 10 - 10) for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD. PMID- 26999118 TI - Resveratrol Inhibition of Cellular Respiration: New Paradigm for an Old Mechanism. AB - Resveratrol (3,4',5-trihydroxy-trans-stilbene, RSV) has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1) decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2) increases adenosine monophosphate/adenosine diphosphate (AMP/ADP) ratio that can lead to AMP protein kinase (AMPK) activation, which is related to its health effects, and (3) increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol. PMID- 26999119 TI - Impact of Lipoprotein Lipase Gene Polymorphism, S447X, on Postprandial Triacylglycerol and Glucose Response to Sequential Meal Ingestion. AB - Lipoprotein lipase (LPL) is a key rate-limiting enzyme for the hydrolysis of triacylglycerol (TAG) in chylomicrons and very low-density lipoprotein. Given that postprandial assessment of lipoprotein metabolism may provide a more physiological perspective of disturbances in lipoprotein homeostasis compared to assessment in the fasting state, we have investigated the influence of two commonly studied LPL polymorphisms (rs320, HindIII; rs328, S447X) on postprandial lipaemia, in 261 participants using a standard sequential meal challenge. S447 homozygotes had lower fasting HDL-C (p = 0.015) and a trend for higher fasting TAG (p = 0.057) concentrations relative to the 447X allele carriers. In the postprandial state, there was an association of the S447X polymorphism with postprandial TAG and glucose, where S447 homozygotes had 12% higher TAG area under the curve (AUC) (p = 0.037), 8.4% higher glucose-AUC (p = 0.006) and 22% higher glucose-incremental area under the curve (IAUC) (p = 0.042). A significant gene-gender interaction was observed for fasting TAG (p = 0.004), TAG-AUC (Pinteraction = 0.004) and TAG-IAUC (Pinteraction = 0.016), where associations were only evident in men. In conclusion, our study provides novel findings of an effect of LPL S447X polymorphism on the postprandial glucose and gender-specific impact of the polymorphism on fasting and postprandial TAG concentrations in response to sequential meal challenge in healthy participants. PMID- 26999121 TI - MicroRNA Expression during Bovine Oocyte Maturation and Fertilization. AB - Successful fertilization and subsequent embryo development rely on complex molecular processes starting with the development of oocyte competence through maturation. MicroRNAs (miRNAs) are small non-coding RNA molecules that function as gene regulators in many biological systems, including the oocyte and embryo. In order to further explore the roles of miRNAs in oocyte maturation, we employed small RNA sequencing as a screening tool to identify and characterize miRNA populations present in pools of bovine germinal vesicle (GV) oocytes, metaphase II (MII) oocytes, and presumptive zygotes (PZ). Each stage contained a defined miRNA population, some of which showed stable expression while others showed progressive changes between stages that were subsequently confirmed by quantitative reverse transcription polymerase chain reaction (RT-PCR). Bta-miR 155, bta-miR-222, bta-miR-21, bta-let-7d, bta-let-7i, and bta-miR-190a were among the statistically significant differentially expressed miRNAs (p < 0.05). To determine whether changes in specific primary miRNA (pri-miRNA) transcripts were responsible for the observed miRNA changes, we evaluated pri-miR-155, -222 and let-7d expression. Pri-miR-155 and -222 were not detected in GV oocytes but pri miR-155 was present in MII oocytes, indicating transcription during maturation. In contrast, levels of pri-let-7d decreased during maturation, suggesting that the observed increase in let-7d expression was likely due to processing of the primary transcript. This study demonstrates that both dynamic and stable populations of miRNAs are present in bovine oocytes and zygotes and extend previous studies supporting the importance of the small RNA landscape in the maturing bovine oocyte and early embryo. PMID- 26999120 TI - Retrospective Study of Metastatic Melanoma and Renal Cell Carcinoma to the Brain with Multivariate Analysis of Prognostic Pre-Treatment Clinical Factors. AB - Patients with brain metastasis from renal cell carcinoma (RCC) or melanoma have historically had very poor prognoses of less than one year. Stereotactic radiosurgery (SRS) can be an effective treatment for patients with these tumors. This study analyzes the effect of pretreatment prognostic factors on overall survival (OS) for RCC and melanoma patients with metastasis to the brain treated with SRS. A total of 122 patients with brain metastases from either RCC or melanoma were grouped by age at brain metastasis diagnosis, whether they received whole brain radiation therapy (WBRT) in addition to SRS, or they underwent surgical resection, Karnofsky Performance Score (KPS), number of brain metastases, and primary tumor. Median survival times for melanoma patients and RCC patients were 8.20 +/- 3.06 and 12.70 +/- 2.63 months, respectively. Patients with >5 metastases had a significantly shorter median survival time (6.60 +/- 2.45 months) than the reference group (1 metastasis, 10.70 +/- 13.40 months, p = 0.024). Patients with KPS <= 60 experienced significantly shorter survival than the reference group (KPS = 90-100), with median survival times of 5.80 +/- 2.46 months (p < 0.001) and 45.20 +/- 43.52 months, respectively. We found a median overall survival time of 12.7 and 8.2 months for RCC and melanoma, respectively. Our study determined that a higher number of brain metastases (>5) and lower KPS were statistically significant predictors of a lower OS prognosis. PMID- 26999122 TI - Identification and Characterization of the Gene CYP340W1 from Plutella xylostella and Its Possible Involvement in Resistance to Abamectin. AB - Abamectin has been used to control the diamondback moth, Plutella xylostella (P. xylostella), which is a major agricultural pest that can rapidly develop resistance against insecticides including abamectin. Although cytochrome P450 has been confirmed to play an important role in resistance in P. xylostella, the specific P450 genes associated with the resistance are unclear. The full-length cDNA of the cytochrome P450 gene CYP340W1 was cloned and characterized in the present study. The cDNA assembly yielded a sequence of 1929 bp, containing the open reading frame (ORF) 1491 bp and encodes a 496-amino acid peptide. CYP340W1 was expressed in all P. xylostella developmental stages but its expression level was highest in larvae and especially in the heads of larvae. The expression of CYP340W1 was significantly higher in an abamectin-resistant strain (ABM-R) than in its susceptible counterpart (ABM-S). In addition, expression of CYP340W1 was increased when the ABM-R strain was exposed to abamectin. When injected into third-stage ABM-R larvae, CYP340W1 dsRNA significantly reduced CYP340W1 expression at 6 h and reduced expression by 83% at 12 h. As a consequence of RNAi, the mortality of the injected abamectin-resistant larvae increased after a 48-h exposure to abamectin. The results indicate that the overexpression of CYP340W1 plays an important role in abamectin resistance in P. xylostella. PMID- 26999123 TI - Biosurfactants: Multifunctional Biomolecules of the 21st Century. AB - In the era of global industrialisation, the exploration of natural resources has served as a source of experimentation for science and advanced technologies, giving rise to the manufacturing of products with high aggregate value in the world market, such as biosurfactants. Biosurfactants are amphiphilic microbial molecules with hydrophilic and hydrophobic moieties that partition at liquid/liquid, liquid/gas or liquid/solid interfaces. Such characteristics allow these biomolecules to play a key role in emulsification, foam formation, detergency and dispersal, which are desirable qualities in different industries. Biosurfactant production is considered one of the key technologies for development in the 21st century. Besides exerting a strong positive impact on the main global problems, biosurfactant production has considerable importance to the implantation of sustainable industrial processes, such as the use of renewable resources and "green" products. Biodegradability and low toxicity have led to the intensification of scientific studies on a wide range of industrial applications for biosurfactants in the field of bioremediation as well as the petroleum, food processing, health, chemical, agricultural and cosmetic industries. In this paper, we offer an extensive review regarding knowledge accumulated over the years and advances achieved in the incorporation of biomolecules in different industries. PMID- 26999124 TI - TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1alpha-Mediated Fatty Acid beta-Oxidation. AB - Autophagy flux deficiency is closely related to the development of hepatic steatosis. Transcription factor E3 (TFE3) is reported to be a crucial gene that regulates autophagy flux and lysosome function. Therefore, we investigated the role of TFE3 in a cell model of hepatic steatosis. We constructed L02 hepatocyte lines that stably over-expressed or knocked down the expression of TFE3. Subsequently, the effects of TFE3 on hepatocellular lipid metabolism were determined by autophagy flux assay, lipid oil red O (ORO) staining, immunofluorescence staining, and mitochondrial beta-oxidation assessment. Finally, we analyzed whether peroxisome proliferative activated receptor gamma coactivator 1alpha (PGC1alpha) was the potential target gene of TFE3 in the regulation of hepatic steatosis using a chromatin immunoprecipitation (CHIP) assay and a luciferase reporter system. We found that overexpression of TFE3 markedly alleviated hepatocellular steatosis. On the contrary, downregulation of TFE3 resulted in an aggravated steatosis. The mechanistic studies revealed that the TFE3-manipulated regulatory effects on hepatocellular steatosis are dependent on autophagy-induced lipophagy and PGC1alpha-mediated fatty acid beta-oxidation because blocking these pathways with an Atg5 small interfering RNA (siRNA) or PGC1alpha siRNA dramatically blunted the TFE3-mediated regulation of steatosis. In conclusion, TFE3 gene provides a novel insight into the treatment of hepatic steatosis and other metabolic disease. PMID- 26999125 TI - First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro. AB - First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP 2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit beta (beta-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and beta-d-galactosidase in a dose dependent manner. We conclude that the alkalinization of the lysosomes' internal milieu induced by haloperidol affects lysosomal functionality. PMID- 26999126 TI - Chemical Elicitor-Induced Modulation of Antioxidant Metabolism and Enhancement of Secondary Metabolite Accumulation in Cell Suspension Cultures of Scrophularia kakudensis Franch. AB - Scrophularia kakudensis is an important medicinal plant with pharmaceutically valuable secondary metabolites. To develop a sustainable source of naturaceuticals with vital therapeutic importance, a cell suspension culture was established in S. kakudensis for the first time. Friable calli were induced from the leaf explants cultured on a Murashige and Skoog (MS) medium containing 3.0 mg.L(-1) 6-benzyladenine (BA) in a combination with 2 mg.L(-1) 2,4 dichlorophenoxy acetic acid (2,4-D). From the callus cultures, a cell suspension culture was initiated and the cellular differentiation was investigated. In addition, the effect of biotic elicitors such as methyl jasmonate (MeJa), salicylic acid (SA), and sodium nitroprusside (SNP) on the accumulation of secondary metabolites and antioxidant properties was demonstrated. Among the elicitors, the MeJa elicited the accumulation of total phenols, flavonoids, and acacetin, a flavonoid compound with multiple pharmaceutical values. Similarly, the higher concentrations of the MeJa significantly modulated the activities of antioxidant enzymes and enhanced the scavenging potentials of free radicals of cell suspension extracts. Overall, the outcomes of this study can be utilized for the large scale production of pharmaceutically important secondary metabolites from S. kakudensis through cell suspension cultures. PMID- 26999127 TI - Evolving Diversity of Hepatitis C Viruses in Yunnan Honghe, China. AB - The Chinese Honghe Autonomous Prefecture (Honghe) in Yunnan Province is a unique ethnic area because it is inhabited by more than ten different minority ethnic groups. Geographically, Honghe directly shares a border with Vietnam. The objective of this study was to investigate genetic diversity and distribution of the Hepatitis C virus (HCV) in Honghe. Ninety nine subjects who were infected with HCV or HCV/HIV (Human Immunodeficiency Virus Type 1) were recruited into this study. HCV genotypes and subtypes were determined based on the sequences of the core/envelope 1 (C/E1) and the nonstructural protein 5B (NS5B) genomic regions. The viral diversity and origins of dissemination were examined by phylogenetic analyses. Three HCV genotypes (1, 3 and 6) with six subtypes (1b, 3b, 3a, 6a, 6n and 6v) were identified. The most predominant form was genotype 3 (54.6%) followed by 6 (34.3%), and 1 (9.1%). The HCV subtype 3b appeared to be the most frequent form (38.4%) followed by 6n (20.2%) and 3a (16.2%). Statistical analyses suggested a possible rise of the genotype 6a in Honghe among intravenous drug users with HCV/HIV co-infections. Further phylogenetic analyses suggested that similar HCV-6a viruses might have been circulating in the Honghe area for more than a decade, which likely originated from Vietnam or vice versa. Two HCV samples with single HCV infection (SC34 and SC45) were isolated that could represent new recombinant variants. Although the genetic prevalence of HCV in Honghe is in general agreement with that of Southwest China and Yunnan Province, the diversity of HCV genotypes and subtypes in Honghe is somewhat unique and evolving. Information presented here should provide useful information for future health surveillance and prevention of HCV infection in this area. PMID- 26999130 TI - Particle Filter with Novel Nonlinear Error Model for Miniature Gyroscope-Based Measurement While Drilling Navigation. AB - The derivation of a conventional error model for the miniature gyroscope-based measurement while drilling (MGWD) system is based on the assumption that the errors of attitude are small enough so that the direction cosine matrix (DCM) can be approximated or simplified by the errors of small-angle attitude. However, the simplification of the DCM would introduce errors to the navigation solutions of the MGWD system if the initial alignment cannot provide precise attitude, especially for the low-cost microelectromechanical system (MEMS) sensors operated in harsh multilateral horizontal downhole drilling environments. This paper proposes a novel nonlinear error model (NNEM) by the introduction of the error of DCM, and the NNEM can reduce the propagated errors under large-angle attitude error conditions. The zero velocity and zero position are the reference points and the innovations in the states estimation of particle filter (PF) and Kalman filter (KF). The experimental results illustrate that the performance of PF is better than KF and the PF with NNEM can effectively restrain the errors of system states, especially for the azimuth, velocity, and height in the quasi-stationary condition. PMID- 26999131 TI - Vision-Based SLAM System for Unmanned Aerial Vehicles. AB - The present paper describes a vision-based simultaneous localization and mapping system to be applied to Unmanned Aerial Vehicles (UAVs). The main contribution of this work is to propose a novel estimator relying on an Extended Kalman Filter. The estimator is designed in order to fuse the measurements obtained from: (i) an orientation sensor (AHRS); (ii) a position sensor (GPS); and (iii) a monocular camera. The estimated state consists of the full state of the vehicle: position and orientation and their first derivatives, as well as the location of the landmarks observed by the camera. The position sensor will be used only during the initialization period in order to recover the metric scale of the world. Afterwards, the estimated map of landmarks will be used to perform a fully vision based navigation when the position sensor is not available. Experimental results obtained with simulations and real data show the benefits of the inclusion of camera measurements into the system. In this sense the estimation of the trajectory of the vehicle is considerably improved, compared with the estimates obtained using only the measurements from the position sensor, which are commonly low-rated and highly noisy. PMID- 26999129 TI - A Novel Pretreatment-Free Duplex Chamber Digital PCR Detection System for the Absolute Quantitation of GMO Samples. AB - Digital polymerase chain reaction (PCR) has developed rapidly since it was first reported in the 1990s. However, pretreatments are often required during preparation for digital PCR, which can increase operation error. The single-plex amplification of both the target and reference genes may cause uncertainties due to the different reaction volumes and the matrix effect. In the current study, a quantitative detection system based on the pretreatment-free duplex chamber digital PCR was developed. The dynamic range, limit of quantitation (LOQ), sensitivity and specificity were evaluated taking the GA21 event as the experimental object. Moreover, to determine the factors that may influence the stability of the duplex system, we evaluated whether the pretreatments, the primary and secondary structures of the probes and the SNP effect influence the detection. The results showed that the LOQ was 0.5% and the sensitivity was 0.1%. We also found that genome digestion and single nucleotide polymorphism (SNP) sites affect the detection results, whereas the unspecific hybridization within different probes had little side effect. This indicated that the detection system was suited for both chamber-based and droplet-based digital PCR. In conclusion, we have provided a simple and flexible way of achieving absolute quantitation for genetically modified organism (GMO) genome samples using commercial digital PCR detection systems. PMID- 26999132 TI - Estimating the Underwater Diffuse Attenuation Coefficient with a Low-Cost Instrument: The KdUINO DIY Buoy. AB - A critical parameter to assess the environmental status of water bodies is the transparency of the water, as it is strongly affected by different water quality related components (such as the presence of phytoplankton, organic matter and sediment concentrations). One parameter to assess the water transparency is the diffuse attenuation coefficient. However, the number of subsurface irradiance measurements obtained with conventional instrumentation is relatively low, due to instrument costs and the logistic requirements to provide regular and autonomous observations. In recent years, the citizen science concept has increased the number of environmental observations, both in time and space. The recent technological advances in embedded systems and sensors also enable volunteers (citizens) to create their own devices (known as Do-It-Yourself or DIY technologies). In this paper, a DIY instrument to measure irradiance at different depths and automatically calculate the diffuse attenuation Kd coefficient is presented. The instrument, named KdUINO, is based on an encapsulated low-cost photonic sensor and Arduino (an open-hardware platform for the data acquisition). The whole instrument has been successfully operated and the data validated comparing the KdUINO measurements with the commercial instruments. Workshops have been organized with high school students to validate its feasibility. PMID- 26999128 TI - The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization. AB - KCNQ (KV7) channels are voltage-gated potassium (KV) channels, and the function of KV7 channels in muscles, neurons, and sensory cells is well established. We confirmed that overall blockade of KV channels with tetraethylammonium augmented the mineralization of bone-marrow-derived human mesenchymal stem cells during osteogenic differentiation, and we determined that KV7.3 was expressed in MG-63 and Saos-2 cells at the mRNA and protein levels. In addition, functional KV7 currents were detected in MG-63 cells. Inhibition of KV7.3 by linopirdine or XE991 increased the matrix mineralization during osteoblast differentiation. This was confirmed by alkaline phosphatase, osteocalcin, and osterix in MG-63 cells, whereas the expression of Runx2 showed no significant change. The extracellular glutamate secreted by osteoblasts was also measured to investigate its effect on MG-63 osteoblast differentiation. Blockade of KV7.3 promoted the release of glutamate via the phosphorylation of extracellular signal-regulated kinase 1/2 mediated upregulation of synapsin, and induced the deposition of type 1 collagen. However, activation of KV7.3 by flupirtine did not produce notable changes in matrix mineralization during osteoblast differentiation. These results suggest that KV7.3 could be a novel regulator in osteoblast differentiation. PMID- 26999133 TI - A Novel Conductive Poly(3,4-ethylenedioxythiophene)-BSA Film for the Construction of a Durable HRP Biosensor Modified with NanoAu Particles. AB - In this study, we have investigated the contribution of bovine serum albumin (BSA) to the durability of the electrochemically synthesized poly(3,4 ethylenedioxythiophene) (PEDOT) film on a platinum (Pt) electrode. The electrode was capable to effectively adsorb the nano Au particles (AuNPs) to form a uniform layout, which was then able to immobilize the horseradish peroxidase (HRP) to construct a functional HRP/AuNPs/PEDOT(BSA)/Pt biosensor. Cyclic voltammetry was employed to evaluate the performance of the biosensor through the measurement of hydrogen peroxide. Our results revealed a satisfied linear correlation between the cathodic current and the concentration of H2O2. Furthermore, the addition of oxidized form of nicotinamide adenine dinucleotide, or NAD+, as the electron transfer mediator in the detection solution could dramatically enhance the sensitivity of detection by about 35.5%. The main advantages of the current biosensor are its durability, sensitivity, reliability, and biocompatibility. PMID- 26999134 TI - A Strip Cell in Pyroelectric Devices. AB - The pyroelectric effect affords the opportunity to convert temporal temperature fluctuations into usable electrical energy in order to develop abundantly available waste heat. A strip pyroelectric cell, used to enhance temperature variation rates by lateral temperature gradients and to reduce cell capacitance to further promote the induced voltage, is described as a means of improving pyroelectric energy transformation. A precision dicing saw was successfully applied in fabricating the pyroelectric cell with a strip form. The strip pyroelectric cell with a high-narrow cross section is able to greatly absorb thermal energy via the side walls of the strips, thereby inducing lateral temperature gradients and increasing temperature variation rates in a thicker pyroelectric cell. Both simulation and experimentation show that the strip pyroelectric cell improves the electrical outputs of pyroelectric cells and enhances the efficiency of pyroelectric harvesters. The strip-type pyroelectric cell has a larger temperature variation when compared to the trenched electrode and the original type, by about 1.9 and 2.4 times, respectively. The measured electrical output of the strip type demonstrates a conspicuous increase in stored energy as compared to the trenched electrode and the original type, by of about 15.6 and 19.8 times, respectively. PMID- 26999136 TI - A New Linear Oscillatory Actuator with Variable Characteristics Using Two Sets of Coils. AB - Nowadays, electromagnetic linear oscillatory actuators are used as vibration control devices because of their high controllability. However, there is a problem that thrust and vibration are small at a wide drive frequency range. In order to improve this problem, we propose a new linear oscillatory actuator that can easily change its own characteristics by using two sets of coils. Through finite element analysis, large vibration was observed at 100 Hz in a series connection, and large vibration and high thrust were observed at 70 Hz and 140 Hz in a parallel connection. From these results, we verified that the actuator had two different characteristics due to switchable connections, and could generate high thrust and large vibration by smaller currents at a wide drive frequency range. PMID- 26999135 TI - Accurate Detection of Rifampicin-Resistant Mycobacterium Tuberculosis Strains. AB - In 2013 alone, the death rate among the 9.0 million people infected with Mycobacterium tuberculosis (TB) worldwide was around 14%, which is unacceptably high. An empiric treatment of patients infected with TB or drug-resistant Mycobacterium tuberculosis (MDR-TB) strain can also result in the spread of MDR TB. The diagnostic tools which are rapid, reliable, and have simple experimental protocols can significantly help in decreasing the prevalence rate of MDR-TB strain. We report the evaluation of the 9G technology based 9G DNAChips that allow accurate detection and discrimination of TB and MDR-TB-RIF. One hundred and thirteen known cultured samples were used to evaluate the ability of 9G DNAChip in the detection and discrimination of TB and MDR-TB-RIF strains. Hybridization of immobilized probes with the PCR products of TB and MDR-TB-RIF strains allow their detection and discrimination. The accuracy of 9G DNAChip was determined by comparing its results with sequencing analysis and drug susceptibility testing. Sequencing analysis showed 100% agreement with the results of 9G DNAChip. The 9G DNAChip showed very high sensitivity (95.4%) and specificity (100%). PMID- 26999137 TI - Developing an Efficient and General Strategy for Immobilization of Small Molecules onto Microarrays Using Isocyanate Chemistry. AB - Small-molecule microarray (SMM) is an effective platform for identifying lead compounds from large collections of small molecules in drug discovery, and efficient immobilization of molecular compounds is a pre-requisite for the success of such a platform. On an isocyanate functionalized surface, we studied the dependence of immobilization efficiency on chemical residues on molecular compounds, terminal residues on isocyanate functionalized surface, lengths of spacer molecules, and post-printing treatment conditions, and we identified a set of optimized conditions that enable us to immobilize small molecules with significantly improved efficiencies, particularly for those molecules with carboxylic acid residues that are known to have low isocyanate reactivity. We fabricated microarrays of 3375 bioactive compounds on isocyanate functionalized glass slides under these optimized conditions and confirmed that immobilization percentage is over 73%. PMID- 26999139 TI - Scalable Indoor Localization via Mobile Crowdsourcing and Gaussian Process. AB - Indoor localization using Received Signal Strength Indication (RSSI) fingerprinting has been extensively studied for decades. The positioning accuracy is highly dependent on the density of the signal database. In areas without calibration data, however, this algorithm breaks down. Building and updating a dense signal database is labor intensive, expensive, and even impossible in some areas. Researchers are continually searching for better algorithms to create and update dense databases more efficiently. In this paper, we propose a scalable indoor positioning algorithm that works both in surveyed and unsurveyed areas. We first propose Minimum Inverse Distance (MID) algorithm to build a virtual database with uniformly distributed virtual Reference Points (RP). The area covered by the virtual RPs can be larger than the surveyed area. A Local Gaussian Process (LGP) is then applied to estimate the virtual RPs' RSSI values based on the crowdsourced training data. Finally, we improve the Bayesian algorithm to estimate the user's location using the virtual database. All the parameters are optimized by simulations, and the new algorithm is tested on real-case scenarios. The results show that the new algorithm improves the accuracy by 25.5% in the surveyed area, with an average positioning error below 2.2 m for 80% of the cases. Moreover, the proposed algorithm can localize the users in the neighboring unsurveyed area. PMID- 26999138 TI - Dual-Phase Lock-In Amplifier Based on FPGA for Low-Frequencies Experiments. AB - Photothermal techniques allow the detection of characteristics of material without invading it. Researchers have developed hardware for some specific Phase and Amplitude detection (Lock-In Function) applications, eliminating space and unnecessary electronic functions, among others. This work shows the development of a Digital Lock-In Amplifier based on a Field Programmable Gate Array (FPGA) for low-frequency applications. This system allows selecting and generating the appropriated frequency depending on the kind of experiment or material studied. The results show good frequency stability in the order of 1.0 * 10(-9) Hz, which is considered good linearity and repeatability response for the most common Laboratory Amplitude and Phase Shift detection devices, with a low error and standard deviation. PMID- 26999140 TI - Road-Aided Ground Slowly Moving Target 2D Motion Estimation for Single-Channel Synthetic Aperture Radar. AB - To detect and estimate ground slowly moving targets in airborne single-channel synthetic aperture radar (SAR), a road-aided ground moving target indication (GMTI) algorithm is proposed in this paper. First, the road area is extracted from a focused SAR image based on radar vision. Second, after stationary clutter suppression in the range-Doppler domain, a moving target is detected and located in the image domain via the watershed method. The target's position on the road as well as its radial velocity can be determined according to the target's offset distance and traffic rules. Furthermore, the target's azimuth velocity is estimated based on the road slope obtained via polynomial fitting. Compared with the traditional algorithms, the proposed method can effectively cope with slowly moving targets partly submerged in a stationary clutter spectrum. In addition, the proposed method can be easily extended to a multi-channel system to further improve the performance of clutter suppression and motion estimation. Finally, the results of numerical experiments are provided to demonstrate the effectiveness of the proposed algorithm. PMID- 26999141 TI - A PetriNet-Based Approach for Supporting Traceability in Cyber-Physical Manufacturing Systems. AB - With the growing popularity of complex dynamic activities in manufacturing processes, traceability of the entire life of every product has drawn significant attention especially for food, clinical materials, and similar items. This paper studies the traceability issue in cyber-physical manufacturing systems from a theoretical viewpoint. Petri net models are generalized for formulating dynamic manufacturing processes, based on which a detailed approach for enabling traceability analysis is presented. Models as well as algorithms are carefully designed, which can trace back the lifecycle of a possibly contaminated item. A practical prototype system for supporting traceability is designed, and a real life case study of a quality control system for bee products is presented to validate the effectiveness of the approach. PMID- 26999142 TI - Validation of Underwater Sensor Package Using Feature Based SLAM. AB - Robotic vehicles working in new, unexplored environments must be able to locate themselves in the environment while constructing a picture of the objects in the environment that could act as obstacles that would prevent the vehicles from completing their desired tasks. In enclosed environments, underwater range sensors based off of acoustics suffer performance issues due to reflections. Additionally, their relatively high cost make them less than ideal for usage on low cost vehicles designed to be used underwater. In this paper we propose a sensor package composed of a downward facing camera, which is used to perform feature tracking based visual odometry, and a custom vision-based two dimensional rangefinder that can be used on low cost underwater unmanned vehicles. In order to examine the performance of this sensor package in a SLAM framework, experimental tests are performed using an unmanned ground vehicle and two feature based SLAM algorithms, the extended Kalman filter based approach and the Rao Blackwellized, particle filter based approach, to validate the sensor package. PMID- 26999143 TI - An Efficient Distributed Coverage Hole Detection Protocol for Wireless Sensor Networks. AB - In wireless sensor networks (WSNs), certain areas of the monitoring region may have coverage holes and serious coverage overlapping due to the random deployment of sensors. The failure of electronic components, software bugs and destructive agents could lead to the random death of the nodes. Sensors may be dead due to exhaustion of battery power, which may cause the network to be uncovered and disconnected. Based on the deployment nature of the nodes in remote or hostile environments, such as a battlefield or desert, it is impossible to recharge or replace the battery. However, the data gathered by the sensors are highly essential for the analysis, and therefore, the collaborative detection of coverage holes has strategic importance in WSNs. In this paper, distributed coverage hole detection algorithms are designed, where nodes can collaborate to detect the coverage holes autonomously. The performance evaluation of our protocols suggests that our protocols outperform in terms of hole detection time, limited power consumption and control packet overhead to detect holes as compared to other similar protocols. PMID- 26999144 TI - Underwater Multi-Vehicle Trajectory Alignment and Mapping Using Acoustic and Optical Constraints. AB - Multi-robot formations are an important advance in recent robotic developments, as they allow a group of robots to merge their capacities and perform surveys in a more convenient way. With the aim of keeping the costs and acoustic communications to a minimum, cooperative navigation of multiple underwater vehicles is usually performed at the control level. In order to maintain the desired formation, individual robots just react to simple control directives extracted from range measurements or ultra-short baseline (USBL) systems. Thus, the robots are unaware of their global positioning, which presents a problem for the further processing of the collected data. The aim of this paper is two-fold. First, we present a global alignment method to correct the dead reckoning trajectories of multiple vehicles to resemble the paths followed during the mission using the acoustic messages passed between vehicles. Second, we focus on the optical mapping application of these types of formations and extend the optimization framework to allow for multi-vehicle geo-referenced optical 3D mapping using monocular cameras. The inclusion of optical constraints is not performed using the common bundle adjustment techniques, but in a form improving the computational efficiency of the resulting optimization problem and presenting a generic process to fuse optical reconstructions with navigation data. We show the performance of the proposed method on real datasets collected within the Morph EU-FP7 project. PMID- 26999145 TI - An Energy-Efficient MAC Protocol for Medical Emergency Monitoring Body Sensor Networks. AB - Medical emergency monitoring body sensor networks (BSNs) monitor the occurrence of medical emergencies and are helpful for the daily care of the elderly and chronically ill people. Such BSNs are characterized by rare traffic when there is no emergency occurring, high real-time and reliable requirements of emergency data and demand for a fast wake-up mechanism for waking up all nodes when an emergency happens. A beacon-enabled MAC protocol is specially designed to meet the demands of medical emergency monitoring BSNs. The rarity of traffic is exploited to improve energy efficiency. By adopting a long superframe structure to avoid unnecessary beacons and allocating most of the superframe to be inactive periods, the duty cycle is reduced to an extremely low level to save energy. Short active time slots are interposed into the superframe and shared by all of the nodes to deliver the emergency data in a low-delay and reliable way to meet the real-time and reliable requirements. The interposition slots can also be used by the coordinator to broadcast network demands to wake-up all nodes in a low delay and energy-efficient way. Experiments display that the proposed MAC protocol works well in BSNs with low emergency data traffic. PMID- 26999146 TI - A Differential Monolithically Integrated Inductive Linear Displacement Measurement Microsystem. AB - An inductive linear displacement measurement microsystem realized as a monolithic Application-Specific Integrated Circuit (ASIC) is presented. The system comprises integrated microtransformers as sensing elements, and analog front-end electronics for signal processing and demodulation, both jointly fabricated in a conventional commercially available four-metal 350-nm CMOS process. The key novelty of the presented system is its full integration, straightforward fabrication, and ease of application, requiring no external light or magnetic field source. Such systems therefore have the possibility of substituting certain conventional position encoder types. The microtransformers are excited by an AC signal in MHz range. The displacement information is modulated into the AC signal by a metal grating scale placed over the microsystem, employing a differential measurement principle. Homodyne mixing is used for the demodulation of the scale displacement information, returned by the ASIC as a DC signal in two quadrature channels allowing the determination of linear position of the target scale. The microsystem design, simulations, and characterization are presented. Various system operating conditions such as frequency, phase, target scale material and distance have been experimentally evaluated. The best results have been achieved at 4 MHz, demonstrating a linear resolution of 20 um with steel and copper scale, having respective sensitivities of 0.71 V/mm and 0.99 V/mm. PMID- 26999147 TI - Node Deployment Algorithm for Underwater Sensor Networks Based on Connected Dominating Set. AB - Existing node deployment algorithms for underwater sensor networks are nearly unable to improve the network coverage rate under the premise of ensuring the full network connectivity and do not optimize the communication and move energy consumption during the deployment. Hence, a node deployment algorithm based on connected dominating set (CDS) is proposed. After randomly sowing the nodes in 3D monitoring underwater space, disconnected nodes move to the sink node until the network achieves full connectivity. The sink node then performs centralized optimization to determine the CDS and adjusts the locations of dominated nodes. Simulation results show that the proposed algorithm can achieve a high coverage rate while ensuring full connectivity and decreases the communication and movement energy consumption during deployment. PMID- 26999148 TI - Mechanical Characterization of Hybrid Vesicles Based on Linear Poly(Dimethylsiloxane-b-Ethylene Oxide) and Poly(Butadiene-b-Ethylene Oxide) Block Copolymers. AB - Poly(dimethylsiloxane-ethylene oxide) (PDMS-PEO) and poly(butadiene-b-ethylene oxide) (PBd-PEO) are two block copolymers which separately form vesicles with disparate membrane permeabilities and fluidities. Thus, hybrid vesicles formed from both PDMS-PEO and PBd-PEO may ultimately allow for systematic, application specific tuning of vesicle membrane fluidity and permeability. However, given the relatively low strength previously noted for comb-type PDMS-PEO vesicles, the mechanical robustness of the resulting hybrid vesicles must first be confirmed. Toward this end, we have characterized the mechanical behavior of vesicles formed from mixtures of linear PDMS-PEO and linear PBd-PEO using micropipette aspiration. Tension versus strain plots of pure PDMS12-PEO46 vesicles revealed a non-linear response in the high tension regime, in contrast to the approximately linear response of pure PBd33-PEO20 vesicles. Remarkably, the area expansion modulus, critical tension, and cohesive energy density of PDMS12-PEO46 vesicles were each significantly greater than for PBd33-PEO20 vesicles, although critical strain was not significantly different between these vesicle types. PDMS12 PEO46/PBd33-PEO20 hybrid vesicles generally displayed graded responses in between that of the pure component vesicles. Thus, the PDMS12-PEO46/PBd33-PEO20 hybrid vesicles retained or exceeded the strength and toughness characteristic of pure PBd-PEO vesicles, indicating that future assessment of the membrane permeability and fluidity of these hybrid vesicles may be warranted. PMID- 26999150 TI - Scene-Level Geographic Image Classification Based on a Covariance Descriptor Using Supervised Collaborative Kernel Coding. AB - Scene-level geographic image classification has been a very challenging problem and has become a research focus in recent years. This paper develops a supervised collaborative kernel coding method based on a covariance descriptor (covd) for scene-level geographic image classification. First, covd is introduced in the feature extraction process and, then, is transformed to a Euclidean feature by a supervised collaborative kernel coding model. Furthermore, we develop an iterative optimization framework to solve this model. Comprehensive evaluations on public high-resolution aerial image dataset and comparisons with state-of-the art methods show the superiority and effectiveness of our approach. PMID- 26999149 TI - Fusion of Haptic and Gesture Sensors for Rehabilitation of Bimanual Coordination and Dexterous Manipulation. AB - Disabilities after neural injury, such as stroke, bring tremendous burden to patients, families and society. Besides the conventional constrained-induced training with a paretic arm, bilateral rehabilitation training involves both the ipsilateral and contralateral sides of the neural injury, fitting well with the fact that both arms are needed in common activities of daily living (ADLs), and can promote good functional recovery. In this work, the fusion of a gesture sensor and a haptic sensor with force feedback capabilities has enabled a bilateral rehabilitation training therapy. The Leap Motion gesture sensor detects the motion of the healthy hand, and the omega.7 device can detect and assist the paretic hand, according to the designed cooperative task paradigm, as much as needed, with active force feedback to accomplish the manipulation task. A virtual scenario has been built up, and the motion and force data facilitate instantaneous visual and audio feedback, as well as further analysis of the functional capabilities of the patient. This task-oriented bimanual training paradigm recruits the sensory, motor and cognitive aspects of the patient into one loop, encourages the active involvement of the patients into rehabilitation training, strengthens the cooperation of both the healthy and impaired hands, challenges the dexterous manipulation capability of the paretic hand, suits easy of use at home or centralized institutions and, thus, promises effective potentials for rehabilitation training. PMID- 26999151 TI - Haptic, Virtual Interaction and Motor Imagery: Entertainment Tools and Psychophysiological Testing. AB - In this work, the perception of affordances was analysed in terms of cognitive neuroscience during an interactive experience in a virtual reality environment. In particular, we chose a virtual reality scenario based on the Leap Motion controller: this sensor device captures the movements of the user's hand and fingers, which are reproduced on a computer screen by the proper software applications. For our experiment, we employed a sample of 10 subjects matched by age and sex and chosen among university students. The subjects took part in motor imagery training and immersive affordance condition (a virtual training with Leap Motion and a haptic training with real objects). After each training sessions the subject performed a recognition task, in order to investigate event-related potential (ERP) components. The results revealed significant differences in the attentional components during the Leap Motion training. During Leap Motion session, latencies increased in the occipital lobes, which are entrusted to visual sensory; in contrast, latencies decreased in the frontal lobe, where the brain is mainly activated for attention and action planning. PMID- 26999153 TI - A Novel Robust Hinfinity Filter Based on Krein Space Theory in the SINS/CNS Attitude Reference System. AB - Owing to their numerous merits, such as compact, autonomous and independence, the strapdown inertial navigation system (SINS) and celestial navigation system (CNS) can be used in marine applications. What is more, due to the complementary navigation information obtained from two different kinds of sensors, the accuracy of the SINS/CNS integrated navigation system can be enhanced availably. Thus, the SINS/CNS system is widely used in the marine navigation field. However, the CNS is easily interfered with by the surroundings, which will lead to the output being discontinuous. Thus, the uncertainty problem caused by the lost measurement will reduce the system accuracy. In this paper, a robust Hinfinity filter based on the Krein space theory is proposed. The Krein space theory is introduced firstly, and then, the linear state and observation models of the SINS/CNS integrated navigation system are established reasonably. By taking the uncertainty problem into account, in this paper, a new robust Hinfinity filter is proposed to improve the robustness of the integrated system. At last, this new robust filter based on the Krein space theory is estimated by numerical simulations and actual experiments. Additionally, the simulation and experiment results and analysis show that the attitude errors can be reduced by utilizing the proposed robust filter effectively when the measurements are missing discontinuous. Compared to the traditional Kalman filter (KF) method, the accuracy of the SINS/CNS integrated system is improved, verifying the robustness and the availability of the proposed robust Hinfinity filter. PMID- 26999152 TI - Employing an Incentive Spirometer to Calibrate Tidal Volumes Estimated from a Smartphone Camera. AB - A smartphone-based tidal volume (V(T)) estimator was recently introduced by our research group, where an Android application provides a chest movement signal whose peak-to-peak amplitude is highly correlated with reference V(T) measured by a spirometer. We found a Normalized Root Mean Squared Error (NRMSE) of 14.998% +/ 5.171% (mean +/- SD) when the smartphone measures were calibrated using spirometer data. However, the availability of a spirometer device for calibration is not realistic outside clinical or research environments. In order to be used by the general population on a daily basis, a simple calibration procedure not relying on specialized devices is required. In this study, we propose taking advantage of the linear correlation between smartphone measurements and V(T) to obtain a calibration model using information computed while the subject breathes through a commercially-available incentive spirometer (IS). Experiments were performed on twelve (N = 12) healthy subjects. In addition to corroborating findings from our previous study using a spirometer for calibration, we found that the calibration procedure using an IS resulted in a fixed bias of -0.051 L and a RMSE of 0.189 +/- 0.074 L corresponding to 18.559% +/- 6.579% when normalized. Although it has a small underestimation and slightly increased error, the proposed calibration procedure using an IS has the advantages of being simple, fast, and affordable. This study supports the feasibility of developing a portable smartphone-based breathing status monitor that provides information about breathing depth, in addition to the more commonly estimated respiratory rate, on a daily basis. PMID- 26999154 TI - Adaptive Transcutaneous Power Transfer to Implantable Devices: A State of the Art Review. AB - Wireless energy transfer is a broad research area that has recently become applicable to implantable medical devices. Wireless powering of and communication with implanted devices is possible through wireless transcutaneous energy transfer. However, designing wireless transcutaneous systems is complicated due to the variability of the environment. The focus of this review is on strategies to sense and adapt to environmental variations in wireless transcutaneous systems. Adaptive systems provide the ability to maintain performance in the face of both unpredictability (variation from expected parameters) and variability (changes over time). Current strategies in adaptive (or tunable) systems include sensing relevant metrics to evaluate the function of the system in its environment and adjusting control parameters according to sensed values through the use of tunable components. Some challenges of applying adaptive designs to implantable devices are challenges common to all implantable devices, including size and power reduction on the implant, efficiency of power transfer and safety related to energy absorption in tissue. Challenges specifically associated with adaptation include choosing relevant and accessible parameters to sense and adjust, minimizing the tuning time and complexity of control, utilizing feedback from the implanted device and coordinating adaptation at the transmitter and receiver. PMID- 26999156 TI - A Micro Aerosol Sensor for the Measurement of Airborne Ultrafine Particles. AB - Particle number concentration and particle size are the two key parameters used to characterize exposure to airborne nanoparticles or ultrafine particles that have attracted the most attention. This paper proposes a simple micro aerosol sensor for detecting the number concentration and particle size of ultrafine particles with diameters from 50 to 253 nm based on electrical diffusion charging. The sensor is composed of a micro channel and a couple of planar electrodes printed on two circuit boards assembled in parallel, which thus integrate charging, precipitating and measurement elements into one chip, the overall size of which is 98 * 38 * 25 mm3. The experiment results demonstrate that the sensor is useful for measuring monodisperse aerosol particles with number concentrations from 300 to 2.5 * 104 /cm3 and particle sizes from 50 to 253 nm. The aerosol sensor has a simple structure and small size, which is favorable for use in handheld devices. PMID- 26999155 TI - The Impacts of Attitudes and Engagement on Electronic Word of Mouth (eWOM) of Mobile Sensor Computing Applications. AB - As one of the latest revolutions in networking technology, social networks allow users to keep connected and exchange information. Driven by the rapid wireless technology development and diffusion of mobile devices, social networks experienced a tremendous change based on mobile sensor computing. More and more mobile sensor network applications have appeared with the emergence of a huge amount of users. Therefore, an in-depth discussion on the human-computer interaction (HCI) issues of mobile sensor computing is required. The target of this study is to extend the discussions on HCI by examining the relationships of users' compound attitudes (i.e., affective attitudes, cognitive attitude), engagement and electronic word of mouth (eWOM) behaviors in the context of mobile sensor computing. A conceptual model is developed, based on which, 313 valid questionnaires are collected. The research discusses the level of impact on the eWOM of mobile sensor computing by considering user-technology issues, including the compound attitude and engagement, which can bring valuable discussions on the HCI of mobile sensor computing in further study. Besides, we find that user engagement plays a mediating role between the user's compound attitudes and eWOM. The research result can also help the mobile sensor computing industry to develop effective strategies and build strong consumer user-product (brand) relationships. PMID- 26999157 TI - A Novel Digital Closed Loop MEMS Accelerometer Utilizing a Charge Pump. AB - This paper presents a novel digital closed loop microelectromechanical system (MEMS) accelerometer with the architecture and experimental evaluation. The complicated timing diagram or complex power supply in published articles are circumvented by using a charge pump system of adjustable output voltage fabricated in a 2P4M 0.35 um complementary metal-oxide semiconductor (CMOS) process, therefore making it possible for interface circuits of MEMS accelerometers to be integrated on a single die on a large scale. The output bitstream of the sigma delta modulator is boosted by the charge pump system and then applied on the feedback comb fingers to form electrostatic forces so that the MEMS accelerometer can operate in a closed loop state. Test results agree with the theoretical formula nicely. The nonlinearity of the accelerometer within +/-1 g is 0.222% and the long-term stability is about 774 ug. PMID- 26999158 TI - Self-Sensing of Damage Progression in Unidirectional Multiscale Hierarchical Composites Subjected to Cyclic Tensile Loading. AB - The electrical sensitivity of glass fiber/multiwall carbon nanotube/vinyl ester hierarchical composites containing a tailored electrically-percolated network to self-sense accumulation of structural damage when subjected to cyclic tensile loading-unloading is investigated. The hierarchical composites were designed to contain two architectures differentiated by the location of the multiwall carbon nanotubes (MWCNTs), viz. MWCNTs deposited on the fibers and MWCNTs dispersed within the matrix. The changes in electrical resistance of the hierarchical composites are associated to their structural damage and correlated to acoustic emissions. The results show that such tailored hierarchical composites are able to self-sense damage onset and accumulation upon tensile loading-unloading cycles by means of their electrical response, and that the electrical response depends on the MWCNT location. PMID- 26999159 TI - Dynamic Human Body Modeling Using a Single RGB Camera. AB - In this paper, we present a novel automatic pipeline to build personalized parametric models of dynamic people using a single RGB camera. Compared to previous approaches that use monocular RGB images, our system can model a 3D human body automatically and incrementally, taking advantage of human motion. Based on coarse 2D and 3D poses estimated from image sequences, we first perform a kinematic classification of human body parts to refine the poses and obtain reconstructed body parts. Next, a personalized parametric human model is generated by driving a general template to fit the body parts and calculating the non-rigid deformation. Experimental results show that our shape estimation method achieves comparable accuracy with reconstructed models using depth cameras, yet requires neither user interaction nor any dedicated devices, leading to the feasibility of using this method on widely available smart phones. PMID- 26999160 TI - Next Generation Air Quality Platform: Openness and Interoperability for the Internet of Things. AB - The widespread diffusion of sensors, mobile devices, social media and open data are reconfiguring the way data underpinning policy and science are being produced and consumed. This in turn is creating both opportunities and challenges for policy-making and science. There can be major benefits from the deployment of the IoT in smart cities and environmental monitoring, but to realize such benefits, and reduce potential risks, there is an urgent need to address current limitations, including the interoperability of sensors, data quality, security of access and new methods for spatio-temporal analysis. Within this context, the manuscript provides an overview of the AirSensEUR project, which establishes an affordable open software/hardware multi-sensor platform, which is nonetheless able to monitor air pollution at low concentration levels. AirSensEUR is described from the perspective of interoperable data management with emphasis on possible use case scenarios, where reliable and timely air quality data would be essential. PMID- 26999161 TI - An Inexpensive, Stable, and Accurate Relative Humidity Measurement Method for Challenging Environments. AB - In this research, an improved psychrometer is developed to solve practical issues arising in the relative humidity measurement of challenging drying environments for meat manufacturing in agricultural and agri-food industries. The design in this research focused on the structure of the improved psychrometer, signal conversion, and calculation methods. The experimental results showed the effect of varying psychrometer structure on relative humidity measurement accuracy. An industrial application to dry-cured meat products demonstrated the effective performance of the improved psychrometer being used as a relative humidity measurement sensor in meat-drying rooms. In a drying environment for meat manufacturing, the achieved measurement accuracy for relative humidity using the improved psychrometer was +/-0.6%. The system test results showed that the improved psychrometer can provide reliable and long-term stable relative humidity measurements with high accuracy in the drying system of meat products. PMID- 26999162 TI - A Priority-Based Adaptive MAC Protocol for Wireless Body Area Networks. AB - In wireless body area networks (WBANs), various sensors and actuators are placed on/inside the human body and connected wirelessly. WBANs have specific requirements for healthcare and medical applications, hence, standard protocols like the IEEE 802.15.4 cannot fulfill all the requirements. Consequently, many medium access control (MAC) protocols, mostly derived from the IEEE 802.15.4 superframe structure, have been studied. Nevertheless, they do not support a differentiated quality of service (QoS) for the various forms of traffic coexisting in a WBAN. In particular, a QoS-aware MAC protocol is essential for WBANs operating in the unlicensed Industrial, Scientific, and Medical (ISM) bands, because different wireless services like Bluetooth, WiFi, and Zigbee may coexist there and cause severe interference. In this paper, we propose a priority based adaptive MAC (PA-MAC) protocol for WBANs in unlicensed bands, which allocates time slots dynamically, based on the traffic priority. Further, multiple channels are effectively utilized to reduce access delays in a WBAN, in the presence of coexisting systems. Our performance evaluation results show that the proposed PA-MAC outperforms the IEEE 802.15.4 MAC and the conventional priority-based MAC in terms of the average transmission time, throughput, energy consumption, and data collision ratio. PMID- 26999163 TI - Activity of Gallium Meso- and Protoporphyrin IX against Biofilms of Multidrug Resistant Acinetobacter baumannii Isolates. AB - Acinetobacter baumannii is a challenging pathogen due to antimicrobial resistance and biofilm development. The role of iron in bacterial physiology has prompted the evaluation of iron-modulation as an antimicrobial strategy. The non-reducible iron analog gallium(III) nitrate, Ga(NO3)3, has been shown to inhibit A. baumannii planktonic growth; however, utilization of heme-iron by clinical isolates has been associated with development of tolerance. These observations prompted the evaluation of iron-heme sources on planktonic and biofilm growth, as well as antimicrobial activities of gallium meso- and protoporphyrin IX (Ga-MPIX and Ga-PPIX), metal heme derivatives against planktonic and biofilm bacteria of multidrug-resistant (MDR) clinical isolates of A. baumannii in vitro. Ga(NO3)3 was moderately effective at reducing planktonic bacteria (64 to 128 uM) with little activity against biofilms (>=512 uM). In contrast, Ga-MPIX and Ga-PPIX were highly active against planktonic bacteria (0.25 to 8 uM). Cytotoxic effects in human fibroblasts were observed following exposure to concentrations exceeding 128 uM of Ga-MPIX and Ga-PPIX. We observed that the gallium metal heme conjugates were more active against planktonic and biofilm bacteria, possibly due to utilization of heme-iron as demonstrated by the enhanced effects on bacterial growth and biofilm formation. PMID- 26999164 TI - Aspergillus Sydowii Marine Fungal Bloom in Australian Coastal Waters, Its Metabolites and Potential Impact on Symbiodinium Dinoflagellates. AB - Dust has been widely recognised as an important source of nutrients in the marine environment and as a vector for transporting pathogenic microorganisms. Disturbingly, in the wake of a dust storm event along the eastern Australian coast line in 2009, the Continuous Plankton Recorder collected masses of fungal spores and mycelia (~150,000 spores/m3) forming a floating raft that covered a coastal area equivalent to 25 times the surface of England. Cultured A. sydowii strains exhibited varying metabolite profiles, but all produced sydonic acid, a chemotaxonomic marker for A. sydowii. The Australian marine fungal strains share major metabolites and display comparable metabolic diversity to Australian terrestrial strains and to strains pathogenic to Caribbean coral. Secondary colonisation of the rafts by other fungi, including strains of Cladosporium, Penicillium and other Aspergillus species with distinct secondary metabolite profiles, was also encountered. Our bioassays revealed that the dust-derived marine fungal extracts and known A. sydowii metabolites such as sydowic acid, sydowinol and sydowinin A adversely affect photophysiological performance (Fv/Fm) of the coral reef dinoflagellate endosymbiont Symbiodinium. Different Symbiodinium clades exhibited varying sensitivities, mimicking sensitivity to coral bleaching phenomena. The detection of such large amounts of A. sydowii following this dust storm event has potential implications for the health of coral environments such as the Great Barrier Reef. PMID- 26999165 TI - Marine Natural Products from New Caledonia--A Review. AB - Marine micro- and macroorganisms are well known to produce metabolites with high biotechnological potential. Nearly 40 years of systematic prospecting all around the New Caledonia archipelago and several successive research programs have uncovered new chemical leads from benthic and planktonic organisms. After species identification, biological and/or pharmaceutical analyses are performed on marine organisms to assess their bioactivities. A total of 3582 genera, 1107 families and 9372 species have been surveyed and more than 350 novel molecular structures have been identified. Along with their bioactivities that hold promise for therapeutic applications, most of these molecules are also potentially useful for cosmetics and food biotechnology. This review highlights the tremendous marine diversity in New Caledonia, and offers an outline of the vast possibilities for natural products, especially in the interest of pursuing collaborative fundamental research programs and developing local biotechnology programs. PMID- 26999167 TI - Unmatched Case-Control Study on Late Presentation of HIV Infection in Santiago, Cape Verde (2004-2011). AB - Access to free antiretroviral therapy (ART) in Sub-Saharan Africa has been steadily increasing over the past decade. However, the success of large-scale ART programmes depends on timely diagnosis and early initiation of HIV care. This study characterizes late presenters to HIV care in Santiago (Cape Verde) between 2004 and 2011, and identifies factors associated with late presentation for care. We defined late presentation as persons presenting to HIV care with a CD4 count below 350 cells/mm3. An unmatched case-control study was conducted using socio demographic and behavioural data of 368 individuals (191 cases and 177 controls) collected through an interviewer-administered questionnaire, comparing HIV patients late and early presented to care. Logistic regression was performed to estimate odds ratio and 95% confidence intervals. Results show that 51.9% were late presenters for HIV. No differences were found in gender distribution, marital status, or access to health services between cases and controls. Participants who undertook an HIV test by doctor indication were more likely to present late compared with those who tested for HIV by their own initiative. Also, individuals taking less time to initiate ART are more likely to present late. This study highlights the need to better understand reasons for late presentation to HIV care in Cape Verde. People in older age groups should be targeted in future approaches focused on late presenters to HIV care. PMID- 26999166 TI - Looking Beyond the Terrestrial: The Potential of Seaweed Derived Bioactives to Treat Non-Communicable Diseases. AB - Seaweeds are a large and diverse group of marine organisms that are commonly found in the maritime regions of the world. They are an excellent source of biologically active secondary metabolites and have been shown to exhibit a wide range of therapeutic properties, including anti-cancer, anti-oxidant, anti inflammatory and anti-diabetic activities. Several Asian cultures have a strong tradition of using different varieties of seaweed extensively in cooking as well as in herbal medicines preparations. As such, seaweeds have been used to treat a wide variety of health conditions such as cancer, digestive problems, and renal disorders. Today, increasing numbers of people are adopting a "westernised lifestyle" characterised by low levels of physical exercise and excessive calorific and saturated fat intake. This has led to an increase in numbers of chronic Non-communicable diseases (NCDs) such as cancer, cardiovascular disease, and diabetes mellitus, being reported. Recently, NCDs have replaced communicable infectious diseases as the number one cause of human mortality. Current medical treatments for NCDs rely mainly on drugs that have been obtained from the terrestrial regions of the world, with the oceans and seas remaining largely an untapped reservoir for exploration. This review focuses on the potential of using seaweed derived bioactives including polysaccharides, antioxidants and fatty acids, amongst others, to treat chronic NCDs such as cancer, cardiovascular disease and diabetes mellitus. PMID- 26999169 TI - The Impact of Gender, Socioeconomic Status and Home Language on Primary School Children's Reading Comprehension in KwaZulu-Natal. AB - The current study constituted part of a larger, longitudinal, South African-based study, namely, The Road and Aircraft Noise Exposure on Children's Cognition and Health (RANCH-South Africa). In the context of a multicultural South Africa and varying demographic variables thereof, this study sought to investigate and describe the effects of gender, socioeconomic status and home language on primary school children's reading comprehension in KwaZulu-Natal. In total, 834 learners across 5 public schools in the KwaZulu-Natal province participated in the study. A biographical questionnaire was used to obtain biographical data relevant to this study, and the Suffolk Reading Scale 2 (SRS2) was used to obtain reading comprehension scores. The findings revealed that there was no statistical difference between males and females on reading comprehension scores. In terms of socioeconomic status (SES), learners from a low socioeconomic background performed significantly better than those from a high socioeconomic background. English as a First Language (EL1) speakers had a higher mean reading comprehension score than speakers who spoke English as an Additional Language (EAL). Reading comprehension is indeed affected by a variety of variables, most notably that of language proficiency. The tool to measure reading comprehension needs to be standardized and administered in more than one language, which will ensure increased reliability and validity of reading comprehension scores. PMID- 26999168 TI - An Evaluation of the Efficacy of Selective Alpha-Blockers in the Treatment of Children with Neurogenic Bladder Dysfunction--Preliminary Findings. AB - The aim of this study was to assess the usefulness of selective alpha1-blockers in children with neurogenic urinary tract dysfunctions and increased leak point pressure (LPP). 14 children from age 6 to 16 years with neurogenic urinary tract dysfunctions (neurogenic bladder) and LPP > 40 cm H2O were enrolled in the study. All patients received a selective alpha1-blocker (doxazosin) for 6-8 weeks with an initial dosage of 0.03 mg/kg. During the observation period the continuation of oral anticholinergics, Clean Intermittent Catheterization (CIC), observation of "urinary dryness" and urinary incontinence periods were recommended. Patients were scheduled for a follow-up visit and urodynamic investigation after 6-8 weeks after the doxazosin therapy was started. In 4 patients, urine leakage occurred at lower pressures; in 9 patients, no significant changes in urine leak point pressures were detected; in 3 patients, there was a significant increase in the bladder capacity; in one patient, deterioration in continence was noted. The differences both in LPP and LPV before and after the treatment were not statistically significant. Our observations are consistent with the conclusions from other studies and showed no evident efficacy of doxazosin in children with neurogenic bladder. PMID- 26999170 TI - A Conceptual Framework for the Assessment of Cumulative Exposure to Air Pollution at a Fine Spatial Scale. AB - Many epidemiological studies examining long-term health effects of exposure to air pollutants have characterized exposure by the outdoor air concentrations at sites that may be distant to subjects' residences at different points in time. The temporal and spatial mobility of subjects and the spatial scale of exposure assessment could thus lead to misclassification in the cumulative exposure estimation. This paper attempts to fill the gap regarding cumulative exposure assessment to air pollution at a fine spatial scale in epidemiological studies investigating long-term health effects. We propose a conceptual framework showing how major difficulties in cumulative long-term exposure assessment could be surmounted. We then illustrate this conceptual model on the case of exposure to NO2 following two steps: (i) retrospective reconstitution of NO2 concentrations at a fine spatial scale; and (ii) a novel approach to assigning the time-relevant exposure estimates at the census block level, using all available data on residential mobility throughout a 10- to 20-year period prior to that for which the health events are to be detected. Our conceptual framework is both flexible and convenient for the needs of different epidemiological study designs. PMID- 26999171 TI - Hepatitis B Virus Vaccination Coverage in Medical, Nursing, and Paramedical Students: A Cross-Sectional, Multi-Centered Study in Greece. AB - Students of health professions are at high risk of hepatitis B Virus (HBV) infection during their clinical training. The aim of this cross-sectional, multi centered study was to investigate the HBV vaccination coverage in Greek medical, nursing, and paramedical students, to look into their attitudes towards the importance of vaccines and to reveal reasons associated with not being vaccinated. A self-completed, anonymous questionnaire was distributed to 2119 students of health professions in Greece, during the academic year 2013-2014. The HBV vaccination coverage of students was high (83%), being higher among medical students (88.1%, vs. 81.4% among nursing and 80.1% among paramedical students; p < 0.001). The vast majority of them (95%) have been vaccinated during childhood. In addition, 30% of the unvaccinated students declared fear over HBV safety. Our results indicate that the healthcare students achieved higher reported immunization rates compared to the currently serving healthcare workers, but also to the students of the last decade. The fact that nursing and paramedical students have lower coverage figures underlines the importance of targeted interventions for the different subgroups of healthcare students in terms of educational programs and screening for HBV markers in order to increase HBV vaccination uptake. PMID- 26999173 TI - Association of Geography and Ambient Air Pollution with Urine Metal Concentrations in Six US Cities: The Multi-Ethnic Study of Atherosclerosis. AB - We investigated the associations of urinary concentrations of antimony, cadmium, tungsten and uranium with geographic locations and with ambient air pollution in 304 adults in the Multi-Ethnic Study of Atherosclerosis from six US cities. After adjustment for sociodemographics, body mass index, and smoking status, urinary cadmium was the highest in Winston-Salem among all study sites (the geometric mean [GM] in Winston-Salem was 0.84 ug/L [95% confidence interval (CI) 0.57 1.22]). The adjusted GMs of urinary tungsten and uranium were highest in Los Angeles (0.11 ug/L [95% CI 0.08-0.16] and 0.019 ug/L [95% CI 0.016-0.023], respectively). The adjusted GM ratio comparing fine particulate matter (PM2.5) tertiles 2 and 3 with the lowest tertile were 1.64 (95% CI 1.05-2.56) and 3.55 (95% CI 2.24-5.63) for tungsten, and 1.18 (95% CI 0.94-1.48) and 1.70 (95% CI 1.34-2.14) for uranium. The results for tungsten remained similar after adjustment for study site. Urinary cadmium, tungsten and uranium concentrations differed by geographic locations in MESA (Multi-Ethnic Study of Atherosclerosis) communities. PM2.5 levels could contribute to geographic differences in tungsten exposure. These findings highlight the need to implement preventive strategies to decrease toxic metal exposure and to evaluate the health effects of chronic exposure to those metals. PMID- 26999172 TI - A Review on the Respiratory System Toxicity of Carbon Nanoparticles. AB - The respiratory system represents the main gateway for nanoparticles' entry into the human body. Although there is a myriad of engineered nanoparticles, carbon nanoparticles/nanotubes (CNPs/CNTs) have received much attention mainly due to their light weight, very high surface area, durability, and their diverse applications. Since their discovery and manufacture over two decades ago, much has been learned about nanoparticles' interactions with diverse biological system models. In particular, the respiratory system has been of great interest because various natural and man-made fibrous particles are known to be responsible for chronic and debilitating lung diseases. In this review, we present up-to-date the literature regarding the effects of CNTs or carbon nanofibers (CNFs) on the human respiratory system with respect to respiratory toxicity pathways and associated pathologies. This article is intended to emphasize the potentially dangerous effects to the human respiratory system if inadequate measures are used in the manufacture, handling, and preparation and applications of CNP or CNP-based products. PMID- 26999174 TI - Modeling Environmental Tobacco Smoke (ETS) Infiltration in Low-Income Multifamily Housing before and after Building Energy Retrofits. AB - Secondhand exposure to environmental tobacco smoke (ETS) in multifamily housing remains a health concern despite strong recommendations to implement non-smoking policies. Multiple studies have documented exposure to ETS in non-smoking units located in buildings with smoking units. However, characterizing the magnitude of ETS infiltration or measuring the impact of building interventions or resident behavior on ETS is challenging due to the complexities of multifamily buildings, which include variable resident behaviors and complex airflows between numerous shared compartments (e.g., adjacent apartments, common hallways, elevators, heating, ventilating and air conditioning (HVAC) systems, stack effect). In this study, building simulation models were used to characterize changes in ETS infiltration in a low income, multifamily apartment building in Boston which underwent extensive building renovations targeting energy savings. Results suggest that exterior wall air sealing can lead to increases in ETS infiltration across apartments, while compartmentalization can reduce infiltration. The magnitude and direction of ETS infiltration depends on apartment characteristics, including construction (i.e., level and number of exterior walls), resident behavior (e.g., window opening, operation of localized exhaust fans), and seasonality. Although overall ETS concentrations and infiltration were reduced post energy-related building retrofits, these trends were not generalizable to all building units. Whole building smoke-free policies are the best approach to eliminate exposure to ETS in multifamily housing. PMID- 26999175 TI - Perceived Organizational Support Impacts on the Associations of Work-Family Conflict or Family-Work Conflict with Depressive Symptoms among Chinese Doctors. AB - As a common mental disorder, depressive symptoms had been studied extensively all over the world. However, positive resources for combating depressive symptoms among Chinese doctors were rarely studied. Our study aimed to investigate the relationships between work-family conflict (WFC) and family-work conflict (FWC) with depressive symptoms among Chinese doctors. Meanwhile, the role of perceived organizational support (POS) in this association was explored at an organizational level. The investigation was conducted between March and April 2014. Questionnaires that measured WFC, FWC, depressive symptoms and POS were distributed to 1200 doctors in Shenyang, China. The final study subjects were 931 doctors (effective response rate: 77.6%). In all analyses, male and female doctors were analyzed separately because of possible gender differences. Hierarchical linear regression analyses were used to examine the moderating role of POS. Baron and Kenny's technique and asymptotic and resampling strategies were used to explore the mediating role of POS on the associations of WFC or FWC with depressive symptoms. WFC and FWC had positive relations with depressive symptoms among doctors. POS played a partial mediating role on the correlation of FWC with depressive symptoms among male doctors, and POS played a partial mediating role on the correlation of WFC with depressive symptoms among female doctors. POS had a positive moderating effect on the relationship between WFC and depressive symptoms among doctors. WFC and FWC could aggravate doctors' depressive symptoms, and POS, as an organizational resource, could fight against doctors' depressive symptoms. When POS functioned as a mediator, FWC had a negative effect on POS, which could increase male doctors' depressive symptoms, and WFC had a negative effect on POS, which could increase female doctors' depressive symptoms. In the meantime, POS, as a moderator, could enhance the effects of WFC on depressive symptoms. PMID- 26999177 TI - Dose-Response Relationship between Cumulative Occupational Lead Exposure and the Associated Health Damages: A 20-Year Cohort Study of a Smelter in China. AB - Long-term airborne lead exposure, even below official occupational limits, has been found to cause lead poisoning at higher frequencies than expected, which suggests that China's existing occupational exposure limits should be reexamined. A retrospective cohort study was conducted on 1832 smelting workers from 1988 to 2008 in China. These were individuals who entered the plant and came into continuous contact with lead at work for longer than 3 months. The dose-response relationship between occupational cumulative lead exposure and lead poisoning, abnormal blood lead, urinary lead and erythrocyte zinc protoporphyrin (ZPP) were analyzed and the benchmark dose lower bound confidence limits (BMDLs) were calculated. Statistically significant positive correlations were found between cumulative lead dust and lead fumes exposures and workplace seniority, blood lead, urinary lead and ZPP values. A dose-response relationship was observed between cumulative lead dust or lead fumes exposure and lead poisoning (p < 0.01). The BMDLs of the cumulative occupational lead dust and fumes doses were 0.68 mg-year/m3 and 0.30 mg-year/m3 for lead poisoning, respectively. The BMDLs of workplace airborne lead concentrations associated with lead poisoning were 0.02 mg/m3 and 0.01 mg/m3 for occupational exposure lead dust and lead fume, respectively. In conclusion, BMDLs for airborne lead were lower than occupational exposure limits, suggesting that the occupational lead exposure limits need re examination and adjustment. Occupational cumulative exposure limits (OCELs) should be established to better prevent occupational lead poisoning. PMID- 26999176 TI - Changes of Sand Fly Populations and Leishmania infantum Infection Rates in an Irrigated Village Located in Arid Central Tunisia. AB - The current spread of zoonotic visceral leishmaniasis (ZVL) throughout arid areas of Central Tunisia is a major public health concern. The main objective of this study is to investigate whether the development of irrigation in arid bio geographical areas in Central Tunisia have led to the establishment of a stable cycle involving sand flies of the subgenus Larroussius and Leishmania infantum, and subsequently to the emergence of ZVL. Sand flies were collected from the village of Saddaguia, a highly irrigated zone located within an arid bio geographical area of Central Tunisia by using modified Centers for Diseases Control (CDC) light traps. Morphological keys were used to identify sand flies. Collected sand flies were pooled with up to 30 specimens per pool according to date and tested by nested Polymerase Chain Reaction (PCR) DNA sequencing from positive pools was used to identify Leishmania spp. A total of 4915 sand flies (2422 females and 2493 males) were collected from Saddaguia in September and in October 2014. Morphological identification confirmed sand flies of the subgenus Larroussius to be predominant. PCR analysis followed by DNA sequencing indicated that 15 pools were infected with L. infantum yielding an overall infection rate of 0.6%. The majority of the infected pools were of sand fly species belonging to subgenus Larroussius. Intense irrigation applied to the arid bio-geographical areas in Central Tunisia is at the origin of the development of an environment capable of sustaining important populations of sand flies of the subgenus Larroussius. This has led to the establishment of stable transmission cycles of L. infantum and subsequently to the emergence of ZVL. PMID- 26999179 TI - Life Course, Green Space and Health: Incorporating Place into Life Course Epidemiology. AB - Researchers interested in the relationships between place and health have been slow to incorporate a life course perspective, probably due to the lack of readily available historical environmental data. This hinders the identification of causal relationships. It also restricts our understanding as to whether there are accumulative effects over the life course and if there are critical periods in people's lives when places are particularly pertinent. This study considers the feasibility of constructing longitudinal data on the availability of urban green space. The suitability of various historical and contemporary data sources is considered, including paper maps, aerial photographs and tabular land use data. Measures of urban green space are created for all neighbourhoods across the Edinburgh region of Scotland at various points during the past 100 years. We demonstrate that it is feasible to develop such measures, but there are complex issues involved in doing so. We also test the utility of the measures via an analysis of how accessibility to green space might alter over the life course of both people, and their residential neighbourhoods. The findings emphasise the potential for utilising historical data to significantly enhance understanding of the relationships between nature and health, and between health and place more generally. We encourage researchers to use data from other locations to consider including a longitudinal perspective to examine relationships between people's health and their environment. PMID- 26999178 TI - Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers. AB - The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID- 26999180 TI - Indicators for Monitoring Water, Sanitation, and Hygiene: A Systematic Review of Indicator Selection Methods. AB - Monitoring water, sanitation, and hygiene (WaSH) is important to track progress, improve accountability, and demonstrate impacts of efforts to improve conditions and services, especially in low- and middle-income countries. Indicator selection methods enable robust monitoring of WaSH projects and conditions. However, selection methods are not always used and there are no commonly-used methods for selecting WaSH indicators. To address this gap, we conducted a systematic review of indicator selection methods used in WaSH-related fields. We present a summary of indicator selection methods for environment, international development, and water. We identified six methodological stages for selecting indicators for WaSH: define the purpose and scope; select a conceptual framework; search for candidate indicators; determine selection criteria; score indicators against criteria; and select a final suite of indicators. This summary of indicator selection methods provides a foundation for the critical assessment of existing methods. It can be used to inform future efforts to construct indicator sets in WaSH and related fields. PMID- 26999182 TI - Erratum: Li, M., et al. Middle East Respiratory Syndrome and Medical Students: Letter from China. Int. J. Environ. Res. Public Health 2015, 12, 13289-13294. PMID- 26999181 TI - Changes in Physiological and Agronomical Parameters of Barley (Hordeum vulgare) Exposed to Cerium and Titanium Dioxide Nanoparticles. AB - The aims of our experiment were to evaluate the uptake and translocation of cerium and titanium oxide nanoparticles and to verify their effects on the growth cycle of barley (Hordeum vulgare L.). Barley plants were grown to physiological maturity in soil enriched with either 0, 500 or 1000 mg . kg(-1) cerium oxide nanoparticles (nCeO2) or titanium oxide nanoparticles (nTiO2) and their combination. The growth cycle of nCeO2 and nTiO2 treated plants was about 10 days longer than the controls. In nCeO2 treated plants the number of tillers, leaf area and the number of spikes per plant were reduced respectively by 35.5%, 28.3% and 30% (p <= 0.05). nTiO2 stimulated plant growth and compensated for the adverse effects of nCeO2. Concentrations of Ce and Ti in aboveground plant fractions were minute. The fate of nanomaterials within the plant tissues was different. Crystalline nTiO2 aggregates were detected within the leaf tissues of barley, whereas nCeO2 was not present in the form of nanoclusters. PMID- 26999183 TI - Polyethyleneimine Capped Silver Nanoclusters as Efficient Antibacterial Agents. AB - Development of efficient antibacterial agents is critical for human health. In the present study, we investigated the antibacterial activity of polyethyleneimine (PEI)-capped silver nanoclusters (PEI-AgNCs), based on the fact that nanoclusters normally have higher surface-to-volume ratios than traditional nanomaterials and PEI itself has a strong antimicrobial capacity. We synthesized stable silver nanoclusters by altering PEI molecular weight from 0.6 kDa to 25 kDa and characterized them by UV-Vis absorption and fluorescence spectroscopy and high resolution transmission electron microscopy. The sizes of AgNCs were around 2 nm in diameter and were little influenced by the molecular weight of PEIs. The antibacterial abilities of the four PEI-AgNCs were explored on agar plate and in liquid systems. Our results revealed that the antibacterial activity of PEI-AgNCs is excellent and the reduction of PEI molecular weight could result in the increased antibacterial capacity of PEI-AgNCs. Such proposed new materials might be useful as efficient antibacterial agents in practical clinical applications. PMID- 26999184 TI - Assessment of the Spatial and Temporal Variations of Water Quality for Agricultural Lands with Crop Rotation in China by Using a HYPE Model. AB - Many water quality models have been successfully used worldwide to predict nutrient losses from anthropogenically impacted catchments, but hydrological and nutrient simulations with limited data are difficult considering the transfer of model parameters and complication of model calibration and validation. This study aims: (i) to assess the performance capabilities of a new and relatively more advantageous model, namely, Hydrological Predictions for the Environment (HYPE), that simulates stream flow and nutrient load in agricultural areas by using a multi-site and multi-objective parameter calibration method and (ii) to investigate the temporal and spatial variations of total nitrogen (TN) and total phosphorous (TP) concentrations and loads with crop rotation by using the model for the first time. A parameter estimation tool (PEST) was used to calibrate parameters. Results show that the parameters related to the effective soil porosity were highly sensitive to hydrological modeling. N balance was largely controlled by soil denitrification processes. P balance was influenced by the sedimentation rate and production/decay of P in rivers and lakes. The model reproduced the temporal and spatial variations of discharge and TN/TP relatively well in both calibration (2006-2008) and validation (2009-2010) periods. Among the obtained data, the lowest Nash-Suttclife efficiency of discharge, daily TN load, and daily TP load were 0.74, 0.51, and 0.54, respectively. The seasonal variations of daily TN concentrations in the entire simulation period were insufficient, indicated that crop rotation changed the timing and amount of N output. Monthly TN and TP simulation yields revealed that nutrient outputs were abundant in summer in terms of the corresponding discharge. The area-weighted TN and TP load annual yields in five years showed that nutrient loads were extremely high along Hong and Ru rivers, especially in agricultural lands. PMID- 26999186 TI - Mitigating Physiological Responses to Layoff Threat: An Experimental Test of the Efficacy of Two Coping Interventions. AB - The purpose of the current study was to assess real-time physiological reactions to the threat of layoffs and to determine whether the use of an emotion-focused vs. problem-focused coping intervention would be more efficacious in attenuating these physiological reactions. A 2 (coping intervention) * 4 (within-subjects time points) mixed experimental design was used to test the hypotheses. Eighty four undergraduates participated in this laboratory experiment during which their galvanic skin response (GSR) and heart rate (HR) were continuously monitored. Analyses indicate that individuals instructed to utilize an emotion-focused coping strategy experienced a significantly greater decline in their GSR compared to those utilizing the problem-focused coping method. Results suggest organizations conducting layoffs might focus first on dealing with the emotional aftermath of downsizing before focusing on problem-solving tasks, such as resume writing and other traditional outplacement activities. PMID- 26999185 TI - Salivary Cortisol Reactivity in Preterm Infants in Neonatal Intensive Care: An Integrative Review. AB - Recently, more and more researchers have been using salivary cortisol reactivity to evaluate stress in preterm infants in the neonatal intensive care unit (NICU). The aim of this integrative literature review was to summarize the evidence of interventions leading to a change in salivary cortisol from the baseline in preterm infants in the NICU. The electronic databases of PubMed, CINAHL, Web of Science, and Scopus were searched for relevant studies. The inclusion criteria were studies with preterm infants exposed to an intervention evaluated by salivary cortisol reactivity before discharge from the NICU, which were published in English. In total, 16 studies were included. Eye-screening examination and heel lance provoked an increase in the salivary cortisol level. Music, prone position, and co-bedding among twins decreased the salivary cortisol level. Several studies reported a low rate of successful saliva sampling or did not use control groups. Future studies need to focus on non-painful interventions in order to learn more about salivary cortisol regulation in preterm infants. Moreover, these studies should use study designs comprising homogenous gestational and postnatal age groups, control groups, and reliable analysis methods that are able to detect cortisol in small amounts of saliva. PMID- 26999187 TI - Alphaherpesvirus Subversion of Stress-Induced Translational Arrest. AB - In this article, we provide an overview of translational arrest in eukaryotic cells in response to stress and the tactics used specifically by alphaherpesviruses to overcome translational arrest. One consequence of translational arrest is the formation of cytoplasmic compartments called stress granules (SGs). Many viruses target SGs for disruption and/or modification, including the alphaherpesvirus herpes simplex virus type 2 (HSV-2). Recently, it was discovered that HSV-2 disrupts SG formation early after infection via virion host shutoff protein (vhs), an endoribonuclease that is packaged within the HSV-2 virion. We review this discovery and discuss the insights it has provided into SG biology as well as its potential significance in HSV-2 infection. A model for vhs mediated disruption of SG formation is presented. PMID- 26999189 TI - Subcellular Trafficking and Functional Relationship of the HSV-1 Glycoproteins N and M. AB - The herpes simplex virus type 1 (HSV-1) glycoprotein N (gN/UL49.5) is a type I transmembrane protein conserved throughout the herpesvirus family. gN is a resident of the endoplasmic reticulum that in the presence of gM is translocated to the trans Golgi network. gM and gN are covalently linked by a single disulphide bond formed between cysteine 46 of gN and cysteine 59 of gM. Exit of gN from the endoplasmic reticulum requires the N-terminal core of gM composed of eight transmembrane domains but is independent of the C-terminal extension of gM. Co-transport of gN and gM to the trans Golgi network also occurs upon replacement of conserved cysteines in gM and gN, suggesting that their physical interaction is mediated by covalent and non-covalent forces. Deletion of gN/UL49.5 using bacterial artificial chromosome (BAC) mutagenesis generated mutant viruses with wild-type growth behaviour, while full deletion of gM/UL10 resulted in an attenuated phenotype. Deletion of gN/UL49.5 in conjunction with various gM/UL10 mutants reduced average plaque sizes to the same extent as either single gM/UL10 mutant, indicating that gN is nonessential for the function performed by gM. We propose that gN functions in gM-dependent as well as gM-independent processes during which it is complemented by other viral factors. PMID- 26999190 TI - Comprehensive Assessments of RNA-seq by the SEQC Consortium: FDA-Led Efforts Advance Precision Medicine. AB - Studies on gene expression in response to therapy have led to the discovery of pharmacogenomics biomarkers and advances in precision medicine. Whole transcriptome sequencing (RNA-seq) is an emerging tool for profiling gene expression and has received wide adoption in the biomedical research community. However, its value in regulatory decision making requires rigorous assessment and consensus between various stakeholders, including the research community, regulatory agencies, and industry. The FDA-led SEquencing Quality Control (SEQC) consortium has made considerable progress in this direction, and is the subject of this review. Specifically, three RNA-seq platforms (Illumina HiSeq, Life Technologies SOLiD, and Roche 454) were extensively evaluated at multiple sites to assess cross-site and cross-platform reproducibility. The results demonstrated that relative gene expression measurements were consistently comparable across labs and platforms, but not so for the measurement of absolute expression levels. As part of the quality evaluation several studies were included to evaluate the utility of RNA-seq in clinical settings and safety assessment. The neuroblastoma study profiled tumor samples from 498 pediatric neuroblastoma patients by both microarray and RNA-seq. RNA-seq offers more utilities than microarray in determining the transcriptomic characteristics of cancer. However, RNA-seq and microarray-based models were comparable in clinical endpoint prediction, even when including additional features unique to RNA-seq beyond gene expression. The toxicogenomics study compared microarray and RNA-seq profiles of the liver samples from rats exposed to 27 different chemicals representing multiple toxicity modes of action. Cross-platform concordance was dependent on chemical treatment and transcript abundance. Though both RNA-seq and microarray are suitable for developing gene expression based predictive models with comparable prediction performance, RNA-seq offers advantages over microarray in profiling genes with low expression. The rat BodyMap study provided a comprehensive rat transcriptomic body map by performing RNA-Seq on 320 samples from 11 organs in either sex of juvenile, adolescent, adult and aged Fischer 344 rats. Lastly, the transferability study demonstrated that signature genes of predictive models are reciprocally transferable between microarray and RNA-seq data for model development using a comprehensive approach with two large clinical data sets. This result suggests continued usefulness of legacy microarray data in the coming RNA-seq era. In conclusion, the SEQC project enhances our understanding of RNA seq and provides valuable guidelines for RNA-seq based clinical application and safety evaluation to advance precision medicine. PMID- 26999188 TI - Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells. AB - The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3C(pro)s) of picornaviruses share similar spatial structures and it is becoming apparent that 3C(pro) plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3C(pro) are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3C(pro) can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3C(pro) and these essential factors, 3C(pro) is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3C(pro) are ongoing and a better understanding of the roles played by 3C(pro) may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3C(pro) is summarized. PMID- 26999191 TI - Perspectives on Transdermal Electroporation. AB - Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID- 26999192 TI - Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice. AB - Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p < 0.05). Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05). Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-gamma increased by 158% and 69%, respectively (p < 0.05), at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic treated polymicrobial sepsis. PMID- 26999193 TI - Comparison of the ISU, NCI, MSM, and SPADE Methods for Estimating Usual Intake: A Simulation Study of Nutrients Consumed Daily. AB - Various methods are available for estimating usual dietary intake distributions. Hence, there is a need for simulation studies to compare them. The methods Iowa State University (ISU), National Cancer Institute (NCI), Multiple Source Method (MSM) and Statistical Program to Assess Dietary Exposure (SPADE) were previously compared in another study, but some results were inconclusive due to the small number of replications used in the simulation. Seeking to overcome this limitation, the present study used 1000 simulated samples for 12 different scenarios to compare the accuracy of estimates yielded by the aforementioned methods. The focus is on scenarios that exhibited the most uncertainty in the conclusions of the mentioned study above, i.e., scenarios with small sample sizes, skewed intake distributions, and large ratios of the between- and within person variances. Bias was used as a measure of accuracy. For scenarios with small sample sizes (n = 150), the ISU, MSM and SPADE methods generally achieved more accurate estimates than the NCI method, particularly for the 10th and 90th percentiles. The differences between methods became smaller with larger sample sizes (n = 300 and n = 500). With few exceptions, the methods were found to perform similarly. PMID- 26999195 TI - The Effect of the Traditional Mediterranean-Style Diet on Metabolic Risk Factors: A Meta-Analysis. AB - The Mediterranean-style diet (MedSD) has gained attention for its positive effects on health outcomes, including metabolic risk factors. However, it is unknown as to which components of MedSD interventions are most beneficial in reducing risk. The objective of this meta-analysis was to obtain effect sizes for metabolic risk factors and explain the variability across the current literature based on study design, sample, and diet characteristics. Six electronic databases were searched from inception until 9 February 2016. Data from 29 studies (N = 4133) were included. There were significant effects in favor of the MedSD for waist circumference, triglycerides, blood glucose, systolic blood pressure, and diastolic blood pressure (d+ = -0.54; d+ = -0.46; d+ = -0.50; d+ = -0.72; d+ = 0.94, respectively). The MedSD was significantly beneficial when the intervention was longer in duration, was conducted in Europe, used a behavioral technique, and was conducted using small groups. The traditional MedSD had significant beneficial effects on five of the six metabolic risk factors. Results from this study provide support for population specific dietary guideline for metabolic risk reduction. PMID- 26999194 TI - Quercetin, Inflammation and Immunity. AB - In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID- 26999196 TI - Detection of 12.5% and 25% Salt Reduction in Bread in a Remote Indigenous Australian Community. AB - Food reformulation is an important strategy to reduce the excess salt intake observed in remote Indigenous Australia. We aimed to examine whether 12.5% and 25% salt reduction in bread is detectable, and, if so, whether acceptability is changed, in a sample of adults living in a remote Indigenous community in the Northern Territory of Australia. Convenience samples were recruited for testing of reduced-salt (300 and 350 mg Na/100 g) versus Standard (~400 mg Na/100 g) white and wholemeal breads (n = 62 for white; n = 72 for wholemeal). Triangle testing was used to examine whether participants could detect a difference between the breads. Liking of each bread was also measured; standard consumer acceptability questionnaires were modified to maximise cultural appropriateness and understanding. Participants were unable to detect a difference between Standard and reduced-salt breads (all p values > 0.05 when analysed using binomial probability). Further, as expected, liking of the breads was not changed with salt reduction (all p values > 0.05 when analysed using ANOVA). Reducing salt in products commonly purchased in remote Indigenous communities has potential as an equitable, cost-effective and sustainable strategy to reduce population salt intake and reduce risk of chronic disease, without the barriers associated with strategies that require individual behaviour change. PMID- 26999197 TI - Tomato Sauce Enriched with Olive Oil Exerts Greater Effects on Cardiovascular Disease Risk Factors than Raw Tomato and Tomato Sauce: A Randomized Trial. AB - Epidemiological studies have observed a negative association between tomato intake and the incidence of cardiovascular disease. As tomato sauces are usually cooked with the addition of oil, some studies have pointed out that both processes may increase the bioavailability of the bioactive compounds. However, the effect of consumption of raw tomatoes and tomato sauces on inflammation biomarkers and adhesion molecules related to atherosclerosis remains unknown. The aim of this study was to test the postprandial effects of a single dose of raw tomatoes (RT), tomato sauce (TS) and tomato sauce with refined olive oil (TSOO) on cardiovascular disease risk factors. We performed an open, prospective, randomized, cross-over, controlled feeding trial in 40 healthy subjects who randomly received: 7.0 g of RT/kg of body weight (BW), 3.5 g of TS/kg BW, 3.5 g of TSOO/Kg BW and 0.25 g of sugar solved in water/kg BW on a single occasion on four different days. Biochemical parameters and cellular and circulating inflammatory biomarkers were assessed at baseline and 6 h after each intervention. The results indicate that, compared to control intervention, a single tomato intake in any form decreased plasma total cholesterol, triglycerides and several cellular and plasma inflammatory biomarkers, and increased plasma high density lipoproteins (HDL) cholesterol and interleukine (IL) 10 concentrations. However, the changes of plasma IL-6 and vascular cell adhesion molecule-1 (VCAM-1), and lymphocyte function-associated antigen-1 (LFA 1) from T-lymphocytes and CD36 from monocytes were significantly greater after TSOO than after RT and TS interventions. We concluded that tomato intake has beneficial effects on cardiovascular risk factors, especially cooked and enriched with oil. PMID- 26999198 TI - Low Urinary Iodine Concentrations Associated with Dyslipidemia in US Adults. AB - Iodine is an essential component of the thyroid hormone which plays crucial roles in healthy thyroid function and lipid metabolism. However, the association between iodine status and dyslipidemia has not been well established at a population level. We aimed to test the hypothesis that the odds of dyslipidemia including elevated total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and apolipoprotein B, and lowered high-density lipoprotein (HDL) cholesterol and HDL/LDL ratio are associated with urinary iodine concentration (UIC) in a population perspective. Data of 2495 US adults (>=20 years) in the National Health and Nutrition Examination Survey 2007-2012 were used in this study. Two subgroups (i.e., UIC below vs. above the 10th percentile) were compared of dyslipidemia as defined based on NCEP ATP III guidelines. The differences between the groups were tested statistically by chi-square test, simple linear regressions, and multiple logistic regressions. Serum lipid concentrations differed significantly between two iodine status groups when sociodemographic and lifestyle covariates were controlled (all, p < 0.05). Those with the lowest decile of UIC were more likely to be at risk for elevated total cholesterol (>200 mg/dL) (adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI): 1.03-2.23) and elevated LDL cholesterol (>130 mg/dL) (AOR = 1.58, 95% CI: 1.11-2.23) and lowered HDL/LDL ratio (<0.4) (AOR = 1.66, 95% CI: 1.18 2.33), compared to those with UIC above the 10th percentile. In US adults, low UIC was associated with increased odds for dyslipidemia. Findings of the present cross-sectional study with spot urine samples highlight the significant association between UIC and serum lipids at population level, but do not substantiate a causal relationship. Further investigations are warranted to elucidate the causal relationship among iodine intakes, iodine status, and serum lipid profiles. PMID- 26999199 TI - Probiotics and Prebiotics: Present Status and Future Perspectives on Metabolic Disorders. AB - Metabolic disorders, including type 2 diabetes (T2DM) and cardiovascular disease (CVD), present an increasing public health concern and can significantly undermine an individual's quality of life. The relative risk of CVD, the primary cause of death in T2DM patients, is two to four times higher in people with T2DM compared with those who are non-diabetic. The prevalence of metabolic disorders has been associated with dynamic changes in dietary macronutrient intake and lifestyle changes over recent decades. Recently, the scientific community has considered alteration in gut microbiota composition to constitute one of the most probable factors in the development of metabolic disorders. The altered gut microbiota composition is strongly conducive to increased adiposity, beta-cell dysfunction, metabolic endotoxemia, systemic inflammation, and oxidative stress. Probiotics and prebiotics can ameliorate T2DM and CVD through improvement of gut microbiota, which in turn leads to insulin-signaling stimulation and cholesterol lowering effects. We analyze the currently available data to ascertain further potential benefits and limitations of probiotics and prebiotics in the treatment of metabolic disorders, including T2DM, CVD, and other disease (obesity). The current paper explores the relevant contemporary scientific literature to assist in the derivation of a general perspective of this broad area. PMID- 26999201 TI - Adverse Events of Intravesical OnabotulinumtoxinA Injection between Patients with Overactive Bladder and Interstitial Cystitis--Different Mechanisms of Action of Botox on Bladder Dysfunction? AB - Intravesical onabotulinumtoxinA (BoNT-A) injections have been proposed to treat both overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) in patients with refractory conditions. We compared adverse events (AEs) after BoNT-A treatment between IC/BPS and OAB in women. IC/BPS patients who failed conventional treatments were enrolled to receive suburothelial injections of BoNT-A (100 U) followed by hydrodistention. Age matched OAB female patients refractory to antimuscarinic agents underwent BoNT-A (100 U) injections. The bladder capacity, maximum flow rate (Qmax), post-void residual (PVR), and voiding efficiency (VE) at baseline, 3 and 6 months, and the post-treatment AEs were analyzed between groups. Finally, 89 IC/BPS and 72 OAB women were included. In the OAB group, the bladder capacity and PVR increased, and VE decreased significantly at three and six months after BoNT-A treatment. In the IC/BPS group, the Qmax increased significantly at six months. There were significant differences in changes of capacity, Qmax, PVR and VE between the two groups. Moreover, OAB patients suffered more frequently from events of hematuria, UTI, and large PVR (>200 mL), but less frequently from events of straining to void. In conclusion, OAB women had higher PVR volume and lower VE than those in IC/BPS after BoNT-A injections. These results imply that the bladder contractility of OAB patients are more susceptible to BoNT-A, which might reflect the different mechanisms of action of Botox on bladder dysfunction. Further investigations to confirm this hypothesis are warranted. PMID- 26999200 TI - Targeting Staphylococcus aureus Toxins: A Potential form of Anti-Virulence Therapy. AB - Staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections. The range of diseases reflects the diversity of virulence factors produced by this pathogen. To establish an infection in the host, S. aureus expresses an inclusive set of virulence factors such as toxins, enzymes, adhesins, and other surface proteins that allow the pathogen to survive under extreme conditions and are essential for the bacteria's ability to spread through tissues. Expression and secretion of this array of toxins and enzymes are tightly controlled by a number of regulatory systems. S. aureus is also notorious for its ability to resist the arsenal of currently available antibiotics and dissemination of various multidrug-resistant S. aureus clones limits therapeutic options for a S. aureus infection. Recently, the development of anti-virulence therapeutics that neutralize S. aureus toxins or block the pathways that regulate toxin production has shown potential in thwarting the bacteria's acquisition of antibiotic resistance. In this review, we provide insights into the regulation of S. aureus toxin production and potential anti-virulence strategies that target S. aureus toxins. PMID- 26999203 TI - Characterization of Enzymatic Activity of MlrB and MlrC Proteins Involved in Bacterial Degradation of Cyanotoxins Microcystins. AB - Bacterial degradation of toxic microcystins produced by cyanobacteria is a common phenomenon. However, our understanding of the mechanisms of these processes is rudimentary. In this paper several novel discoveries regarding the action of the enzymes of the mlr cluster responsible for microcystin biodegradation are presented using recombinant proteins. In particular, the predicted active sites of the recombinant MlrB and MlrC were analyzed using functional enzymes and their inactive muteins. A new degradation intermediate, a hexapeptide derived from linearized microcystins by MlrC, was discovered. Furthermore, the involvement of MlrA and MlrB in further degradation of the hexapeptides was confirmed and a corrected biochemical pathway of microcystin biodegradation has been proposed. PMID- 26999202 TI - Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications. AB - Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of several C. perfringens food- and nonfood-borne human gastrointestinal diseases. The enterotoxin gene (cpe) is located on either the chromosome (for most C. perfringens type A food poisoning strains) or large conjugative plasmids (for the remaining type A food poisoning and most, if not all, other CPE-producing strains). In all CPE-positive strains, the cpe gene is strongly associated with insertion sequences that may help to assist its mobilization and spread. During disease, CPE is produced when C. perfringens sporulates in the intestines, a process involving several sporulation-specific alternative sigma factors. The action of CPE starts with its binding to claudin receptors to form a small complex; those small complexes then oligomerize to create a hexameric prepore on the membrane surface. Beta hairpin loops from the CPE molecules in the prepore assemble into a beta barrel that inserts into the membrane to form an active pore that enhances calcium influx, causing cell death. This cell death results in intestinal damage that causes fluid and electrolyte loss. CPE is now being explored for translational applications including cancer therapy/diagnosis, drug delivery, and vaccination. PMID- 26999204 TI - Maternal Ingestion of Ipomoea carnea: Effects on Goat-Kid Bonding and Behavior. AB - Ipomoea carnea is a toxic plant found in Brazil and other tropical and subtropical countries and often causes poisoning of livestock. The plant contains the alkaloids swainsonine and calystegines, which inhibit key cellular enzymes and cause systematic cell death. This study evaluated the behavioral effects of prenatal ingestion of this plant on dams and their kids. Twenty-four pregnant goats were randomly allocated into four treatment groups and received the following doses (g/kg BW) of fresh I. carnea: 0 (control group), 1.0 (IC1), 3.0 (IC3), and 5.0 (IC5) from day 27 of gestation until parturition. Dam and kid bonding and behavior were evaluated by several tests, immediately after birth until six weeks of age. Dams from IC3 and IC5 groups spent less time paying attention to the newborn. There was a lack of maternal-infant bonding due to I. carnea intoxication. Kids from treated dams had difficulty in standing, suckling, and in recognizing their mother hours after birth. I. carnea can also compromise the kids' ability to learn and to retain spatial memory. We suggest that kids from pregnant goats given I. carnea during gestation have significant behavioral alterations and developmental delays that may compromise their survival. PMID- 26999206 TI - Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain. AB - Loss-of-function mutations of Na(V)1.7 lead to congenital insensitivity to pain, a rare condition resulting in individuals who are otherwise normal except for the inability to sense pain, making pharmacological inhibition of Na(V)1.7 a promising therapeutic strategy for the treatment of pain. We characterized a novel mouse model of Na(V)1.7-mediated pain based on intraplantar injection of the scorpion toxin OD1, which is suitable for rapid in vivo profiling of Na(V)1.7 inhibitors. Intraplantar injection of OD1 caused spontaneous pain behaviors, which were reversed by co-injection with Na(V)1.7 inhibitors and significantly reduced in Na(V)1.7(-/-) mice. To validate the use of the model for profiling Na(V)1.7 inhibitors, we determined the Na(V) selectivity and tested the efficacy of the reported Na(V)1.7 inhibitors GpTx-1, PF-04856264 and CNV1014802 (raxatrigine). GpTx-1 selectively inhibited Na(V)1.7 and was effective when co administered with OD1, but lacked efficacy when delivered systemically. PF 04856264 state-dependently and selectively inhibited Na(V)1.7 and significantly reduced OD1-induced spontaneous pain when delivered locally and systemically. CNV1014802 state-dependently, but non-selectively, inhibited Na(V) channels and was only effective in the OD1 model when delivered systemically. Our novel model of Na(V)1.7-mediated pain based on intraplantar injection of OD1 is thus suitable for the rapid in vivo characterization of the analgesic efficacy of Na(V)1.7 inhibitors. PMID- 26999207 TI - Validation of the Target Protein of Insecticidal Dihydroagarofuran Sesquiterpene Polyesters. AB - A series of insecticidal dihydroagarofuran sesquiterpene polyesters were isolated from the root bark of Chinese bittersweet (Celastrus angulatus Max). A previous study indicated that these compounds affect the digestive system of insects, and aminopeptidase N3 and V-ATPase have been identified as the most putative target proteins by affinity chromatography. In this study, the correlation between the affinity of the compounds to subunit H and the insecticidal activity or inhibitory effect on the activity of V-ATPase was analyzed to validate the target protein. Results indicated that the subunit H of V-ATPase was the target protein of the insecticidal compounds. In addition, the possible mechanism of action of the compounds was discussed. The results provide new ideas for developing pesticides acting on V-ATPase of insects. PMID- 26999208 TI - Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong. AB - In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989 2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data were obtained from Medline search, the Department of Health and the Drug and Poisons Information Bureau. In the New Territories East (where ~20% of the Hong Kong population lived), the incidence of herbal medicines induced anticholinergic poisoning during 1989-1993 was 0.09 per 100,000 population. There were no confirmed cases during 1994-1996. In the whole of Hong Kong, the incidence during 2000-June 2005 was 0.03 per 100,000 population. Contamination of Rhizoma Atractylodis (50%) and erroneous substitution (42%) were the main causes. The incidence during 2008-2012 was 0.06 per 100,000 population. Contamination of non toxic herbs (50%) and erroneous substitution (41%) were the main causes. In Hong Kong, contamination of non-toxic herbs by tropane alkaloids and substitution of Flos Campsis by toxic Flos Daturae Metelis were the predominant causes of herbal medicines induced anticholinergic poisoning. Systematic studies along the supply chain are necessary to identify the likely sources of contamination. If erroneous substitution of Flos Campsis by Flos Daturae Metelis could be prevented, 40% of herbal medicines induced anticholinergic poisoning would not have occurred. Regular inspection of the retailer, continuing education for the staff in the herbal trade and repeated publicity measures will also be required. Pharmacovigilance of herbal medicines should help determine the incidence and causes of adverse reactions and monitor the effectiveness of preventive measures. PMID- 26999209 TI - Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility. AB - We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC). Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB) with urodynamic detrusor overactivity were treated with intravesical injections of 100 U of onabotulinumtoxinA. The overactive bladder symptom score, urgency severity score, patient perception of bladder condition, global response assessment, voiding diary, and procedure related adverse events (AE) at baseline, two weeks, one, three, and six months after treatment were assessed. The results showed that the subjective symptom scores improved significantly in both groups, and the scores did not differ between the groups. The decrease in urgency episodes and urgency urinary incontinence were noted in OAB patients but not in DHIC patients. Although the incidence of AEs was comparable between the groups, the therapeutic efficacy lasted for a mean of 4.9 +/- 4.8 months in DHIC patients and 7.2 +/- 3.3 months in OAB patients (p = 0.03). We concluded that the efficacy of intravesical onabotulinumtoxinA injection for DHIC patients was limited and short-term. Nevertheless, AEs did not increase in DHIC. Intravesical onabotulinumtoxinA might not be a good indication in patients with DHIC and high post-voiding residual urine. Physicians should inform patients of the potential benefits and risks of onabotulinumtoxinA injection for treatment of DHIC. PMID- 26999205 TI - Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications. AB - Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are primary virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications, such as hemolytic uremic syndrome and central nervous system abnormalities. Current therapeutic options to treat patients infected with toxin-producing bacteria are limited. The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. However, in the last decade, numerous studies have demonstrated that in addition to being potent protein synthesis inhibitors, Stxs are also multifunctional proteins capable of activating multiple cell stress signaling pathways, which may result in apoptosis, autophagy or activation of the innate immune response. Here, we briefly present the current understanding of Stx activated signaling pathways and provide a concise review of therapeutic applications to target tumors by engineering the toxins. PMID- 26999210 TI - Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction. AB - Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can encapsulate hydrophilic and hydrophobic drug molecules to be delivered to cells via endocytosis. This review will present new developments on instillations of liposomes and liposome-encapsulated drugs into the urinary bladder for treating lower urinary tract dysfunction. PMID- 26999211 TI - Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy. AB - This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4+ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8+ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4+ Treg cells suppress the efficacy of CAR T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors. PMID- 26999214 TI - Src1 is a Protein of the Inner Nuclear Membrane Interacting with the Dictyostelium Lamin NE81. AB - The nuclear envelope (NE) consists of the outer and inner nuclear membrane (INM), whereby the latter is bound to the nuclear lamina. Src1 is a Dictyostelium homologue of the helix-extension-helix family of proteins, which also includes the human lamin-binding protein MAN1. Both endogenous Src1 and GFP-Src1 are localized to the NE during the entire cell cycle. Immuno-electron microscopy and light microscopy after differential detergent treatment indicated that Src1 resides in the INM. FRAP experiments with GFP-Src1 cells suggested that at least a fraction of the protein could be stably engaged in forming the nuclear lamina together with the Dictyostelium lamin NE81. Both a BioID proximity assay and mis localization of soluble, truncated mRFP-Src1 at cytosolic clusters consisting of an intentionally mis-localized mutant of GFP-NE81 confirmed an interaction of Src1 and NE81. Expression GFP-Src1(1-646), a fragment C-terminally truncated after the first transmembrane domain, disrupted interaction of nuclear membranes with the nuclear lamina, as cells formed protrusions of the NE that were dependent on cytoskeletal pulling forces. Protrusions were dependent on intact microtubules but not actin filaments. Our results indicate that Src1 is required for integrity of the NE and highlight Dictyostelium as a promising model for the evolution of nuclear architecture. PMID- 26999212 TI - Proteomics Analysis Reveals Novel RASSF2 Interaction Partners. AB - RASSF2 is a tumor suppressor that shares homology with other Ras-association domain (RASSF) family members. It is a powerful pro-apoptotic K-Ras effector that is frequently inactivated in many human tumors. The exact mechanism by which RASSF2 functions is not clearly defined, but it likely acts as a scaffolding protein, modulating the activity of other pro-apoptotic effectors, thereby regulating and integrating tumor suppressor pathways. However, only a limited number of RASSF2 interacting partners have been identified to date. We used a proteomics based approach to identify additional RASSF2 interactions, and thereby gain a better insight into the mechanism of action of RASSF2. We identified several proteins, including C1QBP, Vimentin, Protein phosphatase 1G and Ribonuclease inhibitor that function in diverse biological processes, including protein post-translational modifications, epithelial-mesenchymal transition, cell migration and redox homeostasis, which have not previously been reported to interact with RASSF2. We independently validated two of these novel interactions, C1QBP and Vimentin and found that the interaction with C1QBP was enhanced by K Ras whereas, interestingly, the Vimentin interaction was reduced by K-Ras. Additionally, RASSF2/K-Ras regulated the acetylation of Vimentin. Our data thus reveal novel mechanisms by which RASSF2 may exert its functions, several of which may be Ras-regulated. PMID- 26999213 TI - The Regulation of NF-kappaB Subunits by Phosphorylation. AB - The NF-kappaB transcription factor is the master regulator of the inflammatory response and is essential for the homeostasis of the immune system. NF-kappaB regulates the transcription of genes that control inflammation, immune cell development, cell cycle, proliferation, and cell death. The fundamental role that NF-kappaB plays in key physiological processes makes it an important factor in determining health and disease. The importance of NF-kappaB in tissue homeostasis and immunity has frustrated therapeutic approaches aimed at inhibiting NF-kappaB activation. However, significant research efforts have revealed the crucial contribution of NF-kappaB phosphorylation to controlling NF-kappaB directed transactivation. Importantly, NF-kappaB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF kappaB for therapeutic benefit. This review will focus on the phosphorylation of the NF-kappaB subunits and the impact on NF-kappaB function. PMID- 26999215 TI - Codon Distribution in Error-Detecting Circular Codes. AB - In 1957, Francis Crick et al. suggested an ingenious explanation for the process of frame maintenance. The idea was based on the notion of comma-free codes. Although Crick's hypothesis proved to be wrong, in 1996, Arques and Michel discovered the existence of a weaker version of such codes in eukaryote and prokaryote genomes, namely the so-called circular codes. Since then, circular code theory has invariably evoked great interest and made significant progress. In this article, the codon distributions in maximal comma-free, maximal self complementary C3 and maximal self-complementary circular codes are discussed, i.e., we investigate in how many of such codes a given codon participates. As the main (and surprising) result, it is shown that the codons can be separated into very few classes (three, or five, or six) with respect to their frequency. Moreover, the distribution classes can be hierarchically ordered as refinements from maximal comma-free codes via maximal self-complementary C(3) codes to maximal self-complementary circular codes. PMID- 26999217 TI - Insecticide Resistance in Fleas. AB - Fleas are the major ectoparasite of cats, dogs, and rodents worldwide and potential vectors of animal diseases. In the past two decades the majority of new control treatments have been either topically applied or orally administered to the host. Most reports concerning the development of insecticide resistance deal with the cat flea, Ctenocephalides felis felis. Historically, insecticide resistance has developed to many of the insecticides used to control fleas in the environment including carbamates, organophosphates, and pyrethroids. Product failures have been reported with some of the new topical treatments, but actual resistance has not yet been demonstrated. Failures have often been attributed to operational factors such as failure to adequately treat the pet and follow label directions. With the addition of so many new chemistries additional monitoring of flea populations is needed. PMID- 26999216 TI - Coevolution Theory of the Genetic Code at Age Forty: Pathway to Translation and Synthetic Life. AB - The origins of the components of genetic coding are examined in the present study. Genetic information arose from replicator induction by metabolite in accordance with the metabolic expansion law. Messenger RNA and transfer RNA stemmed from a template for binding the aminoacyl-RNA synthetase ribozymes employed to synthesize peptide prosthetic groups on RNAs in the Peptidated RNA World. Coevolution of the genetic code with amino acid biosynthesis generated tRNA paralogs that identify a last universal common ancestor (LUCA) of extant life close to Methanopyrus, which in turn points to archaeal tRNA introns as the most primitive introns and the anticodon usage of Methanopyrus as an ancient mode of wobble. The prediction of the coevolution theory of the genetic code that the code should be a mutable code has led to the isolation of optional and mandatory synthetic life forms with altered protein alphabets. PMID- 26999218 TI - Adhesive Pili in UTI Pathogenesis and Drug Development. AB - Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting 150 million people each year worldwide. High recurrence rates and increasing antimicrobial resistance among uropathogens are making it imperative to develop alternative strategies for the treatment and prevention of this common infection. In this Review, we discuss how understanding the: (i) molecular and biophysical basis of host-pathogen interactions; (ii) consequences of the molecular cross-talk at the host pathogen interface in terms of disease progression; and (iii) pathophysiology of UTIs is leading to efforts to translate this knowledge into novel therapeutics to treat and prevent these infections. PMID- 26999222 TI - Characteristics of Excitable Dog Behavior Based on Owners' Report from a Self Selected Study. AB - Past research has found that excitable dog behavior is prevalent among sheltered and owned dogs and many times is a reason for canine relinquishment. In spite of its prevalence in the canine population, excitable behavior is relatively unstudied in the scientific literature. The intent of this research was to understand the experience of owners of excitable dogs through the analysis of self-administered online questionnaires completed by owners as part of another study. We found that certain daily scenarios tended to prompt excitable behavior, with excitability most common when the owner or other people came to the dog's home. All owners experienced some level of frustration with their dog's excitable behavior, with the majority being very frustrated. Many dogs in the sample had other behavior problems, with disobedient, destructive, chasing and barking behaviors being the most commonly reported. Other characteristics of excitable dogs also are discussed. Although the ability to generalize from these results is likely limited, due to targeted recruitment and selection of owners of more excitable dogs, this research provides valuable insights into the owner's experience of excitable behavior. We hope this study prompts more research into canine excitable behavior which would expand our understanding of this behavior and help behaviorists, veterinarians, and shelters develop tools for managing it, as well as provide better education to owners of excitable dogs. PMID- 26999220 TI - Evasion of Neutrophil Killing by Staphylococcus aureus. AB - Staphylococcus aureus causes many types of infections, ranging from self resolving skin infections to severe or fatal pneumonia. Human innate immune cells, called polymorphonuclear leukocytes (PMNs or neutrophils), are essential for defense against S. aureus infections. Neutrophils are the most prominent cell type of the innate immune system and are capable of producing non-specific antimicrobial molecules that are effective at eliminating bacteria. Although significant progress has been made over the past few decades, our knowledge of S. aureus-host innate immune system interactions is incomplete. Most notably, S. aureus has the capacity to produce numerous molecules that are directed to protect the bacterium from neutrophils. Here we review in brief the role played by neutrophils in defense against S. aureus infection, and correspondingly, highlight selected S. aureus molecules that target key neutrophil functions. PMID- 26999219 TI - The T Cell Response to Staphylococcus aureus. AB - Staphylococcus aureus (S. aureus) is a dangerous pathogen and a leading cause of both nosocomial and community acquired bacterial infection worldwide. However, on the other hand, we are all exposed to this bacterium, often within the first hours of life, and usually manage to establish equilibrium and coexist with it. What does the adaptive immune system contribute toward lifelong control of S. aureus? Will it become possible to raise or enhance protective immune memory by vaccination? While in the past the S. aureus-specific antibody response has dominated this discussion, the research community is now coming to appreciate the role that the cellular arm of adaptive immunity, the T cells, plays. There are numerous T cell subsets, each with differing functions, which together have the ability to orchestrate the immune response to S. aureus and hence to tip the balance between protection and pathology. This review summarizes the state of the art in this dynamic field of research. PMID- 26999221 TI - The Host's Reply to Candida Biofilm. AB - Candida spp. are among the most common nosocomial fungal pathogens and are notorious for their propensity toward biofilm formation. When growing on a medical device or mucosal surface, these organisms reside as communities embedded in a protective matrix, resisting host defenses. The host responds to Candida biofilm by depositing a variety of proteins that become incorporated into the biofilm matrix. Compared to free-floating Candida, leukocytes are less effective against Candida within a biofilm. This review highlights recent advances describing the host's response to Candida biofilms using ex vivo and in vivo models of mucosal and device-associated biofilm infections. PMID- 26999223 TI - Numbers and Characteristics of Cats Admitted to Royal Society for the Prevention of Cruelty to Animals (RSPCA) Shelters in Australia and Reasons for Surrender. AB - Despite high numbers of cats admitted to animal shelters annually, there is surprisingly little information available about the characteristics of these cats. In this study, we examined 195,387 admissions to 33 Australian RSPCA shelters and six friends of the RSPCA groups from July 2006 to June 2010. The aims of this study were to describe the numbers and characteristics of cats entering Australian RSPCA shelters, and to describe reasons for cat surrender. Data collected included shelter, state, admission source, age, gender, date of arrival, color, breed, reproductive status (sterilized or not prior to admission), feral status and surrender reason (if applicable). Most admissions were presented by members of the general public, as either stray animals or owner surrenders, and more kittens were admitted than adults. Owner-related reasons were most commonly given for surrendering a cat to a shelter. The most frequently cited owner-related reason was accommodation (i.e., cats were not allowed). Importantly, although the percentage of admissions where the cat was previously sterilized (36%) was the highest of any shelter study reported to date, this was still lower than expected, particularly among owner-surrendered cats (47%). The percentage of admissions where the cat was previously sterilized was low even in jurisdictions that require mandatory sterilization. PMID- 26999224 TI - Intermittent Suckling Causes a Transient Increase in Cortisol That Does Not Appear to Compromise Selected Measures of Piglet Welfare and Stress. AB - This study tested the hypothesis that piglets subjected to intermittent suckling (IS) would show changes in physiological and behavioral indices indicative of compromised welfare in the peri-weaning period. A total of 21 primiparous sows and their litters were allocated to either a control treatment (n = 10) where piglets were weaned conventionally, or an IS treatment (n = 11) where piglets were separated daily from their sows for 8 h starting the week before weaning. Performance, physiological and behavioral measures were taken at various time points during the week before and after weaning. Plasma cortisol levels were higher (p = 0.01) in IS piglets 7 d before weaning. Regardless of treatment, the N:L ratio at 3 d and 7 d after weaning was higher (p < 0.05) than that at 1 d before weaning. The IS piglets ate more creep feed during lactation (p < 0.05), and there was a tendency for the IS piglets to gain more weight between 3 d and 7 d after weaning (p < 0.1). This study showed that, aside from an increase in cortisol at the start of IS, piglets subjected to IS did not display physiological or behavioral changes indicative of compromised welfare. PMID- 26999226 TI - Thimerosal-Preserved Hepatitis B Vaccine and Hyperkinetic Syndrome of Childhood. AB - (1) BACKGROUND: Hyperkinetic syndrome of childhood (HKSoC) is an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) category in which the majority of the children are also diagnosed under the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), where the umbrella term is "Attention-Deficit and Disruptive Behavior Disorders". The diagnostic criteria for HKSoC are developmentally inappropriate inattention, hyperactivity, and impulsivity. Some studies have implicated mercury (Hg) exposure as a risk factor. (2) METHODS: This hypothesis testing study; using the Vaccine Safety Datalink; assessed the toxicological effects of bolus exposure to organic-Hg from Thimerosal-containing vaccines (TCVs) by examining the relationship between Thimerosal-preserved hepatitis B vaccines (TM-HepB) given at varying levels and at specific intervals in the first six months after birth and the risk of a child being diagnosed with HKSoC. (3) RESULTS: Children diagnosed with HKSoC were significantly more likely to be exposed to increased organic-Hg from TM-HepB doses given within the first month (odds ratio = 1.45; 95% confidence interval (CI) = 1.30-1.62); within the first two months (odds ratio = 1.43; 95% CI = 1.28-1.59); and within the first six months (odds ratio = 4.51; 95% CI = 3.04-6.71) than controls. (4) CONCLUSION: The results indicate that increasing organic-Hg exposure from TCVs heightens the risk of a HKSoC diagnosis. PMID- 26999225 TI - Sexuality (and Lack Thereof) in Adolescence and Early Adulthood: A Review of the Literature. AB - Youth sexuality has been primarily studied with a focus on its potential public health issues, such as sexually transmitted infections and unwanted pregnancies, and its comorbidity with other risky behaviors. More recently, it has been studied as a normative step in romantic partnerships, either pre- or post marital, as well as outside the context of romantic involvement. In this paper, we review the extensive literature on sexuality in adolescence and early adulthood both within and outside romantic relationships (i.e., casual sexual relationships and experiences; CSREs). Furthermore, the recent recognition of youth sexuality as a developmental task has led to a renewed interest from scholars in youth who abstain from sexual encounters, whether deliberately or not. A brief overview of the literature on cultural differences in sexuality, and sexual-minority youth sexual development is also provided. This paper concludes by suggesting future directions to bring the field of youth sexuality and romantic relationships forward. PMID- 26999227 TI - Antioxidant and Antiglycating Constituents from Leaves of Ziziphus oxyphylla and Cedrela serrata. AB - Ziziphus oxyphylla and Cedrela Serrata plants have a folkloric use in Pakistan for treatments of different ailments, i.e., Jaundice, Hepatitis, Diabetes, and antimicrobial. Until now, none of the research studies have reported any phytochemical work on leaves of these two plants. This study aimed to isolate and perform phytochemical analysis in order to search for the constituent having the active role in treatment of the aforementioned ailments. A bioassay-guided fractionation and isolation procedure was used to isolate the concerned phytochemicals present in leaf extracts of Z. oxyphylla and C. serrata. The process involved the hyphenated techniques, i.e., Flash Chromatography, Semi Preparative HPLC/DAD, UPLC/MS, and NMR in order to isolate and elucidate the structure of the phytochemicals. Seven compounds (1-7) were isolated and identified as flavonoids, more in particular glycosides of quercetin and kaempferol. They showed DPPH scavenging activity, compound 3 (isoquercitrin) being the most active one with an IC50 of 10.8 ug/mL (positive control quercetin; IC50 3.6 ug/mL). The superoxide-radical scavenging and total antioxidant (ABTS) assays indicated IC50 values ranging from 200 to 910 ug/mL and 170 to 320 ug/mL, respectively (positive control quercetin: 374 and 180 ug/mL, respectively). Furthermore, these compounds had low IC50 values for inhibition of protein glycation (AGEs inhibition), ranging from 530 to 818 ug/mL, comparable to aminoguanidine (510 ug/mL) used as a positive control. This study resulted in the identification of seven flavonoid glycosides for the first time from the leaves of Z. oxyphylla and C. serrata with antioxidative and antiglycating activities. PMID- 26999228 TI - Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract. AB - Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT) can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papillomaviruses (HPV). The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA) along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8+ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8+ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV specific immunity in the FRT. These results support the application of the needle free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT. PMID- 26999229 TI - Computational Investigation of the Effect of Lipid Membranes on Ion Permeation in Gramicidin A. AB - Membrane proteins are embedded in a lipid bilayer and interact with the lipid molecules in subtle ways. This can be studied experimentally by examining the effect of different lipid bilayers on the function of membrane proteins. Understanding the causes of the functional effects of lipids is difficult to dissect experimentally but more amenable to a computational approach. Here we perform molecular dynamics simulations and free energy calculations to study the effect of two lipid types (POPC and NODS) on the conductance of the gramicidin A (gA) channel. A larger energy barrier is found for the K+ potential of mean force in gA embedded in POPC compared to that in NODS, which is consistent with the enhanced experimental conductance of cations in gA embedded in NODS. Further analysis of the contributions to the potential energy of K+ reveals that gA and water molecules in gA make similar contributions in both bilayers but there are significant differences between the two bilayers when the lipid molecules and interfacial waters are considered. It is shown that the stronger dipole moments of the POPC head groups create a thicker layer of interfacial waters with better orientation, which ultimately is responsible for the larger energy barrier in the K+ PMF in POPC. PMID- 26999231 TI - Mineralization at Titanium Surfaces is a Two-Step Process. AB - Mapping the initial reaction of implants with blood or cell culture medium is important for the understanding of the healing process in bone. In the present study, the formation of low crystalline carbonated hydroxyapatite (CHA) onto commercially pure titanium (Ti) implants from cell culture medium and blood, is described as an early event in bone healing at implants. The Ti-implants were incubated with cell culture medium (DMEM) or whole blood and the surface concentration of Ca, P and HA was analyzed by XPS, EDX and Tof-SIMS. After incubation with DMEM for 16 h and 72 h, EDX and XPS analysis showed stable levels of Ca and P on the Ti-surface. ESEM images showed an even distribution of Ca and P. Further analysis of the XPS results indicated that CHA was formed at the implants. Analysis with ToF-SIMS yielded high m.w. fragments of HA, such as Ca2PO4 at m/z 174.9 and Ca3PO5 at m/z 230.8, as secondary ions at the Ti surfaces. Analysis of implants incubated in blood for 16 h, with ToF-SIMS, showed initial formation of CHA yielding CaOH as secondary ion. The results indicate that early mineralization at Ti-surfaces is an important step in the healing of implants into bone. PMID- 26999230 TI - Hepatic Stellate Cells and microRNAs in Pathogenesis of Liver Fibrosis. AB - microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by either blocking translation or inducing degradation of target mRNA. miRNAs play essential roles in diverse biological and pathological processes, including development of hepatic fibrosis. Hepatic stellate cells (HSCs) play a central role in development of hepatic fibrosis and there are intricate regulatory effects of miRNAs on their activation, proliferation, collagen production, migration, and apoptosis. There are multiple differentially expressed miRNAs in activated HSCs, and in this review we aim to summarize current data on miRNAs that participate in the development of hepatic fibrosis. Based on this review, miRNAs may serve as biomarkers for diagnosis of liver disease, as well as markers of disease progression. Most importantly, dysregulated miRNAs may potentially be targeted by novel therapies to treat and reverse progression of hepatic fibrosis. PMID- 26999232 TI - Multi-Wire Tri-Gate Silicon Nanowires Reaching Milli-pH Unit Resolution in One Micron Square Footprint. AB - The signal-to-noise ratio of planar ISFET pH sensors deteriorates when reducing the area occupied by the device, thus hampering the scalability of on-chip analytical systems which detect the DNA polymerase through pH measurements. Top down nano-sized tri-gate transistors, such as silicon nanowires, are designed for high performance solid-state circuits thanks to their superior properties of voltage-to-current transduction, which can be advantageously exploited for pH sensing. A systematic study is carried out on rectangular-shaped nanowires developed in a complementary metal-oxide-semiconductor (CMOS)-compatible technology, showing that reducing the width of the devices below a few hundreds of nanometers leads to higher charge sensitivity. Moreover, devices composed of several wires in parallel further increase the exposed surface per unit footprint area, thus maximizing the signal-to-noise ratio. This technology allows a sub milli-pH unit resolution with a sensor footprint of about 1 um2, exceeding the performance of previously reported studies on silicon nanowires by two orders of magnitude. PMID- 26999233 TI - Sensing of Salivary Glucose Using Nano-Structured Biosensors. AB - The anxiety and pain associated with frequent finger pricking has always been troublesome for diabetics measuring blood glucose (BG) in their daily lives. For this reason, a reliable glucose monitoring system that allows noninvasive measurements is highly desirable. Our main objective is to develop a biosensor that can detect low-level glucose in saliva (physiological range 0.5-20 mg/dL). Salivary glucose (SG) sensors were built using a layer-by-layer self-assembly of single-walled carbon nanotubes, chitosan, gold nanoparticles, and glucose oxidase onto a screen-printed platinum electrode. An electrochemical method was utilized for the quantitative detection of glucose in both buffer solution and saliva samples. A standard spectrophotometric technique was used as a reference method to validate the glucose content of each sample. The disposable glucose sensors have a detection limit of 0.41 mg/dL, a sensitivity of 0.24 MUA.s.dL.mg(-1), a linear range of 0.5-20 mg/dL in buffer solution, and a response time of 30 s. A study of 10 healthy subjects was conducted, and SG levels between 1.1 to 10.1 mg/dL were successfully detected. The results revealed that the noninvasive SG monitoring could be an alternative for diabetes self-management at home. This paper is not intended to replace regular BG tests, but to study SG itself as an indicator for the quality of diabetes care. It can potentially help patients control and monitor their health conditions, enabling them to comply with prescribed treatments for diabetes. PMID- 26999234 TI - Cortical motor representation of the rectus femoris does not differ between the left and right hemisphere. AB - Transcranial magnetic stimulation (TMS) involves non-invasive magnetic stimulation of the brain, and can be used to explore the corticomotor excitability and motor representations of skeletal muscles. However there is a lack of motor mapping studies in the lower limb and few conducted in healthy cohorts. The cortical motor representations of muscles can vary between individuals in terms of center position and area despite having a general localized region within the motor cortex. It is important to characterize the normal range for these variables in healthy cohorts to be able to evaluate changes in clinical populations. TMS was used in this cross-sectional study to assess the active motor threshold (AMT) and cortical representation area for rectus femoris in 15 healthy individuals (11M/4F 27.3+/-5.9years). No differences were found between hemispheres (Left vs. Right P=0.130) for AMT. In terms of y axis center position no differences were found between hemispheres (Left vs. Right P=0.539), or for the x-axis center position (Left vs. Right P=0.076). Similarly, no differences in calculated area of the motor representation were found (Left vs. Right P=0.699) indicating symmetry between hemispheres. PMID- 26999235 TI - Accuracy of Different Mini Nutritional Assessment Reduced Forms to Evaluate the Nutritional Status of Elderly Hospitalised Diabetic Patients. AB - BACKGROUND: Disease-associated malnutrition (DAM) is a health problem involving all sanitary levels, especially hospitalised elderly patients. Different MNA (Mini Nutritional Assessment)-based forms have been validated in different settings, but it remains unclear if they are appropriate to evaluate the nutritional status of geriatric hospitalised patients with diabetes. OBJECTIVE: The aim of this work was to analyse the accuracy of several MNA reduced forms to detect malnutrition in hospitalised elderly diabetic patients. METHODS: A multicentre observational study was carried out in diabetic patients, who were over the age of 65, from 35 Spanish hospitals. Principal component analysis (PCA) selected the minimal components to elaborate the newly-proposed reduced new version of the MNA (r-MNA). Cohen's Kappa index (KI), with its 95% confidence interval (CI), was used to measure the agreement between the different reduced forms (r-MNA, MNA-SF-BMI, MNA-SF-CC, m-MNA) with the original MNA. RESULTS: Five hundred and ninety-one elderly diabetic patients were included in the study. ROC analysis determined the following cut-off points for the newly proposed r MNA: 0 <10 "malnourished", 10-12 "at risk" and >12-15 "well-nourished". The upper cut off point demonstrated a sensitivity of 87.7%, a specificity of 78.3% and an area under the curve of 0.93. The lower cut-off point showed a sensitivity of 95.9%, a specificity of 78.3% and an area under the curve of 0.95. The best agreement with the original MNA was observed for the MNA-SF-BMI (Kappa index 80.7; 95% CI: 77.4 84) and the worst for the r-MNA (Kappa index 72; 95% CI: 68.2-75.4). CONCLUSIONS: This study found that MNA-SF-BMI is the most accurate screening tool for determining the nutritional status of hospitalised diabetic elderly patients. This is an easy-to-use, fast screening tool with a low risk of misclassification. PMID- 26999236 TI - Relation among 25(OH)D, Aquatic Exercises, and Multifunctional Fitness on Functional Performance of Elderly Women from the Community. AB - OBJECTIVES: The aim of this study was to investigate if there is a relation among 25(OH)D, aquatic training, and multifunctional fitness on functional performance of elderly woman from the community. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: We evaluated elderly women aged >= 60 years (67+/-5 years old). One-hundred eighty were engaged in aquatic training (AT), 119 in multifunctional fitness (MF) for at least one year, and sedentary group (SED) with 162 independent elderly women from the community centers who had not practicing any regular physical exercise at least one year before. MEASUREMENTS: Timed up-and-go (TUG), 2-minute step test (2MST), 30-second chair stand (CS), arm curl (AC), functional reach test (FRT), unipedal balance test (UB) with visual control, handgrip right (HR) and handgrip left (HL) portable dynamometer for strength hip flexors (Hip strength) and knee extensors (Knee strength), serum 25(OH)D, intact parathyroid hormone (PTH), and creatinine clearance. RESULTS: Physical and functional tests showed differences among the three groups (ST; TUG, CS, AC, FR and USB = p <0.001). The PTH and the TUG test correlated inversely with 25(OH)D (r = -0.29 - p <0.001/ r = - 0.16 - p <0.001), also between 25(OH)D and BMI for AT and MF groups respectively (r= -0,15; p=0,04/ r= - 0,19; p=0,036). The AC test showed positive correlation (r = 0, 1 - p <0.001). The age and 25(OH)D were controlled and assumed to be a covariates in the statistical analysis that employed ANCOVA. There was difference on the performance of TUG test (p= 0.049). CONCLUSION: TUG performance was associated with age, exercise type and serum levels of 25(OH)D. The 25(OH)D insufficiency was common in elderly women from subtropical areas. PMID- 26999237 TI - Age-related Changes in Energy Intake and Weight in Community-dwelling Middle-aged and Elderly Japanese. AB - OBJECTIVE: This study attempts to describe trends in energy intake and weight change over 12 years according to age at first participation in the study. DESIGN: Prospective cohort study. SETTING: The National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA), a community-based study. PARTICIPANTS: Participants included 922 men and 879 women who participated in the first study-wave (age 40-79 years) and also participated in at least one study wave from the second to seventh study-wave. Each study-wave was conducted biennially. For individuals, the entire follow-up period was 12 years. MEASUREMENTS: Energy intake was calculated from 3-day dietary records with photographs. Weight and height were measured under a fasting state. To estimate linear changes in energy intake and weight over 12 years according to age at first study-wave, we used the mixed-effects model. RESULTS: Mean (SD) follow-up time and number of study-wave visits were 9.5 (3.7) years and 5.4 (1.8) times, respectively. The fixed effect of the interaction of age and time in energy intake and weight was statistically or marginally statistically significant both in men (p<0.01) and in women (p<0.06). In men, when energy intake was estimated according to age, the rate of decrease in energy intake increased from -6.8 to 33.8 kcal/year for ages 40-79 years. In women, the rate of decrease in energy intake slightly increased in older age groups (-9.1 to -16.7 kcal/year for ages 40-79 years). Weight increased in males in their 40s (0.07 kg/year from age 40) and started to decline by age 53. In women, weight started to decline around age 47 (-0.04 kg/year). CONCLUSION: Twelve-year longitudinal data showed energy intake declined both in men and women in their 40s, and the rate of decrease increased in older males. Weight started to decline in men in their mid-50s and women in their late 40s. Further studies that focus on energy intake and weight reduction are needed to prevent weight loss or underweight in an increasingly aging society. PMID- 26999238 TI - Collaborative Evaluation of the Healthy Habits Program: An Effective Community Intervention to Improve Mobility and Cognition of Chinese Older Adults Living in the U.S. AB - OBJECTIVES: There is a growing demand to reduce ethnic health disparities. The Healthy Habits Program (HHP) was implemented to provide a community-based physical activity and education intervention for Chinese older adults living in Boston, Massachusetts. This study evaluated the HHP by assessing outcomes that are critical for maintaining independence of older persons. DESIGN, SETTING AND PARTICIPANTS: Quantitative evaluation was performed on 50 Chinese older adults enrolled in the HHP. The community members were trained in data collection and management. MEASUREMENTS: Cognition (Mini Mental State Examination (MMSE), Trail Making Test and Complex Walking Task), mobility (Short Physical Performance Battery (SPPB) and maximal gait speed), depressive symptoms (Patient Health Questionnaire-9), perceived disability (World Health Organization Disability Assessment 2.0), nutritional status (Mini Nutrition Assessment(r)), and strength (grip and leg strength) were assessed at baseline and at 6 months. All tests were translated into Chinese. RESULTS: Of the 50 participants (mean age 68.4 years; 68% female), 78% achieved the goal of performing exercise >=3 times/week. After 6 months, clinically meaningful improvements were observed in mobility (mean SPPB score changed from 10.3 to 11.1 points; p=0.01) and cognition (mean MMSE score changed from 26.0 to 27.8 points; p=0.001). There were also statistically significant improvements in executive function, depressive symptoms and perceived disability (p<0.05). CONCLUSION: Culturally sensitive community interventions, such as the HHP, are effective for improving mobility and cognition of Chinese older adults. This reveals the potential of promoting successful aging in minority populations through community settings, and should be advocated to reduce ethnic health disparities in the U.S. PMID- 26999239 TI - Effects of Acetylcholinesterase Inhibitors on Nutritional Status in Elderly Patients with Dementia: A 6-month Follow-up Study. AB - OBJECTIVES: Nutritional status is one of the factors that affects disease progression, morbidity and mortality in elderly patients with dementia. The present study aimed to evaluate the effect of acetylcholinesterase inhibitor (AchEI) therapy on nutritional status and food intake in the elderly. DESIGN, SETTING AND PARTICIPANTS: Newly diagnosed patients with dementia, who underwent comprehensive geriatric assessment (CGA) and were followed at regular intervals, were retrospectively evaluated. A total of 116 patients, who began to receive AchEI therapy and completed 6-month follow-up period under this treatment, were enrolled in the study. MEASUREMENTS: Socio-demographic characteristics and data on comorbidity, polypharmacy, cognitive function, depression, activities of daily living and nutritional status (weight, Body Mass Index (BMI), Mini Nutritional Assessment (MNA)-Short Form) were recorded. RESULTS: The mean age of the patients was 78.0+/-8.9 years. There was no significant difference between baseline and 6 month BMI, weight and MNA scores of dementia patients who received AchEI therapy (p>0.05). With regard to the relation between changes in BMI, weight and MNA on the 6th month versus baseline, and donepezil, rivastigmine and galantamine therapies, no difference was determined (p>0.05). However, no worsening in food intake was observed (kappa: 0.377). When the effects of each AchEI on food intake were compared, food intake in rivastigmine treated patients was not decreased as much as it was in galantamine or donepezil treated patients (p<0.05). CONCLUSION: AchEI therapy has no unfavorable effect on nutritional status or weight in elderly patients with different types of dementia, but it seems that food intake is better in those treated by rivastigmine patch. PMID- 26999240 TI - Association between Fish Intake and Depressive Symptoms among Community-living Older Chinese Adults in Singapore: A Cross-sectional Study. AB - OBJECTIVE: Our aim of this study was to investigate the association between fish consumption and depressive symptoms in senior ethnic Chinese residents of Singapore. DESIGN: A population-based cross-sectional study. SETTING: The Singapore Longitudinal Aging Studies (SLAS). PARTICIPANT: The study consisted of 2,034 participants from the Singapore Longitudinal Aging Studies (SLAS) project who were at least 55 years old. MEASUREMENTS: The presence of depressive symptoms was compared between those who self-reported eating fish at least three times a week versus those who ate fish less often. A score of 5 or greater on the 15-item Geriatric Depression Scale (GDS-15) was the cutoff for being designated as having depressive symptoms. RESULTS: Fish intake was associated with a lower prevalence of depressive symptoms ([odds ratio] OR = 0.60, 95% [confidence interval] CI 0.40 0.90; P = .015) after controlling for age, sex, marital status, housing, smoking, alcohol consumption, physical exercise, social and productive activities, self rated health, hypertension, diabetes, heart failure or attack, stroke, fruit and vegetable intake, and Mini-Mental State Examination (MMSE) scores. CONCLUSION: Our results suggest that eating fish at least three times a week is associated with a lower odds of having depressive symptoms among Chinese adults over 55 years old living in Singapore. PMID- 26999242 TI - Association between the Mediterranean-style Dietary Pattern Score and Physical Performance: Results from TRELONG Study. AB - OBJECTIVE: To determine the association between Mediterranean-Style Dietary Pattern Score and physical performance. DESIGN: Data analysis of a longitudinal study of a representative, age stratified, population sample. SETTING: The TREVISO LONGEVA (TRELONG) Study, in Treviso, Italy. PARTICIPANTS: In 2010, 123 men and 181 women, age 77 years and over (mean age 86.3 +/- 6.8 years). MEASUREMENTS: Performing a logistic regression in a multivariate analysis, hand grip strength and Short Physical Performance Battery (SPPB) were tested in relation to Mediterranean-Style Dietary Pattern Score (MSDPS). RESULTS: The hand grip mean value was 10.9 kg (+/- 9.5) and the SPPB score was 6.3 (+/- 3.8). The MSDPS mean value in this study sample was 38.1/100 (+/- 8.1). A significant association (p=0.036) between a high adherence to the Mediterranean diet (fourth quartile) and higher performance lower limbs (SPPB>7) was found. No correlation was reported for the hand grip strength. CONCLUSION: We found an association statistically significant between a high adherence to the Mediterranean diet and higher physical performance. PMID- 26999243 TI - Keto-supplemented Low Protein Diet: A Valid Therapeutic Approach for Patients with Steroid-resistant Proteinuria during Early-stage Chronic Kidney Disease. AB - BACKGROUND AND OBJECTIVES: Low protein diets supplemented with keto acid (sLPD) are recommended for patients with stage 3-5 chronic kidney disease (CKD). This study assessed whether sLPD is beneficial for patients with steroid-resistant proteinuria during early-stage CKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A 1-year randomized controlled trial was conducted from 2010 to 2012. In this study, 108 proteinuric patients who were steroid-resistant were assigned to a sLPD group (0.6 g/kg/d with 0.09 g/kg/d keto acids) or a normal protein diet group (NPD, 1.0 g/kg/d). Estimated dietary protein intake, urinary protein excretion, remission rate, renal function, nutritional status, and blood pressure were measured. RESULTS: Baseline characteristics were comparable between the sLPD group (47 patients) and the NPD group (49 patients). Urinary protein excretion significantly decreased in sLPD compared to NPD in months 6, 9, and 12 (P<0.05). Proteinuria reduction was higher in sLPD than in NPD (P<0.001) at the end of the study. Complete remission and partial remission rates were higher in sLPD than in NPD. Serum albumin and pre-albumin levels were higher in sLPD than in NPD in months 9 and 12 (P<0.05). Serum total cholesterol and triglyceride levels declined more significantly in sLPD than in NPD (P<0.01) at the end of the study. There were no differences in nutritional status, renal function, hemoglobin, or blood pressure between the two groups. CONCLUSIONS: sLPD is both nutritionally safe and beneficial, providing nephroprotective effects for early stage CKD patients with steroid-resistant proteinuria. PMID- 26999241 TI - Impact of Age-related Comorbidities on Five-year Overall Mortality among Elderly HIV-Infected Patients in the Late HAART Era--Role of Chronic Renal Disease. AB - OBJECTIVES: To identify main prognostic factors for 5-year mortality among age related comorbidities (ARCs) in older people living with HIV (PLHIV). DESIGN: A prospective, multicentre cohort study with a 5-year follow-up period in the late HAART era (from January 2008 to December 2012). SETTING: The Dat'AIDS cohort involving 12 French hospitals. PARTICIPANTS: All actively followed HIV-1 infected patients aged 60 or older. MEASUREMENTS: The study endpoint was all-cause five year mortality. The following ARCs were considered: chronic renal disease, cardiovascular diseases, cancer, chronic pulmonary disease, cirrhosis, diabetes and nutritional status. Hepatitis C (HCV), hepatitis B (HBV) co-infection and sociodemographic characteristics were also evaluated. Cox's Proportional Hazards model was used for multivariate analysis. RESULTS: Among 1415 PLHIV aged 60 or more patients included, mean age was 66+/-5.5 years; 154 died (mortality rate 2.47/100 patient-years). The most prevalent ARCs were chronic renal disease (20.1%), diabetes (14.2%) and cardiovascular diseases (12.2%). By multivariate analysis, chronic renal disease (adjusted hazard ratio (aHR)=2.25; 95% confidence interval (CI) [1.58-2.21]; p<10-4), cardiovascular diseases (aHR=2.40; 95%CI[1.64 3.52]; p<10-4), non-HIV related cancer (aHR=1.91; 95%CI[1.20-3.05]; p=0.007), cirrhosis (aHR=2.99; 95%CI[1.68-5.33]; p<10-3), HCV co-infection (aHR=2.00; 95%CI[1.18-3.38]; p=0.009), low body mass index (aHR=2.42; 95%CI[1.46-4.01]; p<10 3) and CD4 cell count < 200 cells/ul (aHR=2.23; 95%CI[1.36-3.65]; p=0.002) were independently associated with 5 year mortality. CONCLUSION: Due to a high prevalence, chronic renal disease and cardiovascular disease are main prognostic factors for 5-year mortality among aged PLHIV. PMID- 26999244 TI - Evaluation of a Continuing Educational Intervention for Primary Health Care Professionals about Nutritional Care of Patients at Home. AB - OBJECTIVE: Evaluate the effectiveness of a continuing educational intervention on primary health care professionals' familiarity with information important to nutritional care in a palliative phase, their collaboration with other caregivers, and their level of knowledge about important aspects of nutritional care. DESIGN: Observational cohort study. SETTING: 10 primary health care centers in Stockholm County, Sweden. PARTICIPANTS: 140 district nurses/registered nurses and general practitioners/physicians working with home care. INTERVENTION: 87 professionals participated in the intervention group (IG) and 53 in the control group (CG). The intervention consisted of a web-based program offering factual knowledge; a practical exercise linking existing and new knowledge, abilities, and skills; and a case seminar facilitating reflection. MEASUREMENTS: The intervention's effects were measured by a computer-based study-specific questionnaire before and after the intervention, which took approximately 1 month. The CG completed the questionnaire twice (1 month between response occasions). The intervention effects, odds ratios, were estimated by an ordinal logistic regression. RESULTS: In the intra-group analyses, statistically significant changes occurred in the IG's responses to 28 of 32 items and the CG's responses to 4 of 32 items. In the inter-group analyses, statistically significant effects occurred in 20 of 32 statements: all 14 statements that assessed familiarity with important concepts and all 4 statements about collaboration with other caregivers but only 2 of the 14 statements concerning level of knowledge. The intervention effect varied between 2.5 and 12.0. CONCLUSION: The intervention was effective in increasing familiarity with information important to nutritional care in a palliative phase and collaboration with other caregivers, both of which may create prerequisites for better nutritional care. However, the intervention needs to be revised to better increase the professionals' level of knowledge about important aspects of nutritional care. PMID- 26999246 TI - Three Different Outcomes in Older Community-dwelling Patients Receiving Intermediate Care in Nursing Home after Acute Hospitalization. AB - OBJECTIVES: To evaluate the recovery and outcome of older communitydwelling patients admitted to intermediate care (IC) in nursing homes after acute hospitalization, and to compare patients who were able and unable to return directly to their own homes. DESIGN: Prospective, observational, cohort study conducted between June 2011 and 2014. SETTING: A 19- bed IC unit in a nursing home with increased multidisciplinary staffing. PARTICIPANTS: A total of 961 community-dwelling patients, >=70 years of age, considered to have a rehabilitation potential and no major cognitive impairment or delirium, transferred from internal medicine, cardiac, pulmonary and orthopaedic hospital departments. MEASUREMENTS: Demographic data, clinical information, comprehensive geriatric assessment (CGA), discharge destination and length of stay. Residence status and mortality 1 month, 2 months, 3 months, and 6 months after discharge from the hospital. RESULTS: The trajectory of recovery was divided into 3 groups: 1) Rapid recovery, able to return home after median 14 days in IC (n=785, 82%); 2) Slow recovery, requiring additional transfer to other nursing home after IC, but still able to return home within 2 months (n=106, 11%). 3) Poor recovery, requiring transfer to other nursing home after IC and still in a nursing home or dead at 2 months (n=66, 7%). Significant different clinical characteristics were demonstrated between the patients in the 3 groups. After 6 months, the recovery of patients with rapid or slow recovery was similar, 87% were living at home, compared to only 20% of the patients with poor recovery. In multiple logistic regression analysis, slow or poor recovery was significantly associated with low scores on the Barthel index and orthopaedic admission diagnosis. CONCLUSIONS: Although the majority of patients selected for treatment in the IC unit were able to recover and return home, a group of patients needed extra time, up to 2 months, to recover and another group had a poor chance of recovering and returning home. Different caring pathways for different patient groups may be considered in the PAC setting. PMID- 26999245 TI - Defining Rehabilitation Success in Older Adults with Dementia--Results from an Inpatient Geriatric Rehabilitation Unit. AB - OBJECTIVE: To quantify the magnitude of functional recovery in older adults with and without dementia admitted to an inpatient geriatric rehabilitation program by measuring change in measures of global physical function and physical therapy treatment outcomes. DESIGN: Retrospective cohort study. SETTING: Rehabilitation academic hospital. PARTICIPANTS: Consecutive subjects, with (N=65, age 81.9+/-6.0 y) and without (N=157, age 82.8+/-7.2 y) a dementia diagnosis, had assessment data at admission and discharge from inpatient geriatric rehabilitation unit. INTERVENTIONS: Not applicable. MEASUREMENTS: The Functional Independence Measure (FIM) was used to estimate level of independence on activities of daily living. The Berg Balance Scale (BBS), Timed Up and Go Test (TUG) and 2 Minute Walk Test (2MWT) were used to estimate functional mobility and endurance. The FIM (total, motor subscale, cognitive subscale scores) were used to calculate rehabilitation efficacy and efficiency scores. RESULTS: After controlling for confounding, there was no group difference for gains on the BBS, TUG, 2MWT; there was no group difference on rehabilitation efficacy and efficiency values based on the FIM motor subscale. The magnitude of the rehabilitation gain using the total FIM score was statistically different between groups, people with dementia having smaller gains. CONCLUSION: Older adults with a diagnosis of dementia are capable of making motor function recovery during inpatient sub-acute rehabilitation comparable to their peers without a dementia diagnosis. The metric used to evaluate functional recovery influences the determination of rehabilitation success between groups. Rehabilitation success should be defined among people with a dementia diagnosis by a change in the motor subscale of the FIM, rather than the total FIM score or the gain relative to the maximal FIM score. PMID- 26999247 TI - Risk Factors for the Discontinuation of Home Medical Care among Low-functioning Older Patients. AB - OBJECTIVES: Older patients receiving home medical care often have declining functional status and multiple disease conditions. It is important to identify the risk factors for care transition events in this population in order to avoid preventable transitions. In the present study, therefore, we investigated the factors associated with discontinuation of home medical care as a potentially preventable care transition event in older patients. METHODS: Baseline data for participants in the Observational study of Nagoya Elderly with HOme MEdical (ONEHOME) study and data on the mortality, institutionalization, or hospitalisation of the study participants during a 2-year follow-up period were used. Discontinuation of home care was defined as admission to a hospital for any reason, institutionalization, or death. Univariate and multivariate Cox hazard models were used to assess the association of each of the factors with the discontinuation of home care during the observational period. The covariates included in the multivariate analysis were those significantly associated with the discontinuation of home care at the level of P<0.05 in the univariate analysis. RESULTS: The univariate Cox hazard model revealed that a low hemoglobin level (< 11g/dL), low serum albumin level (< 3g/dL), higher Charlson Comorbidity Index score, and low Mini Nutritional Assessment Short Form score (< 7) were significantly associated with the discontinuation of home care. A multivariate Cox hazard model including these four factors demonstrated that all four were independently associated with home-care discontinuation. CONCLUSIONS: The present results demonstrated that anemia, hypoalbuminemia, malnourishment, and the presence of serious comorbidities were associated with the discontinuation of home medical care among low-functioning older patients. PMID- 26999248 TI - Malnutrition and Laboratory Markers in Geriatric Patients. A Comparison of Neurologic-psychiatric, Internal and Trauma Surgical Diseases. AB - OBJECTIVES: There is minimal information on malnutrition in neurologic psychiatric patients compared to internal and trauma-surgical patients. The aim of the present study was to explore if there is a correlation of these different disease groups with the nutritional assessment and biochemical markers. DESIGN: Cross - sectional study. SETTING AND PARTICIPANTS: The study was done in a department of geriatric medicine with subspecialisation in neurologic diseases and stroke unit. 338 patients (m / f = 136 / 202, mean age 81.4 +/- 7.3 years) were evaluated. MEASUREMENTS: The nutritional status was evaluated by using the short form of the Mini Nutritional Assessment (MNA-SF) and seven biochemical markers (hemoglobin, iron, ferritin, vitamin B 12, folic acid, albumin and cholinesterase) were measured. RESULTS: There were 74 (22%) patients with MNA <= 7 points (malnutrition), 148 (44%) patients with an MNA 8 - 11 points (risk of malnutrition) and 116 (34%) patients with an MNA >= 12 points (good nutritional status). The mean MNA score of the three major disease groups trauma-surgery, internal medicine and neurology-psychiatry was 9.1 +/- 3.2 vs. 9.9 +/- 3.1 vs. 10.0 +/- 2.8 (p=0.236). There were significant differences of laboratory markers between the disease groups. A deficit of albumin, cholinesterase and hemoglobin was found more often in trauma-surgical and internal patients than in neurological-psychiatric patients (albumin: 21.4%, 15.7%, 5.3%; p=0.001; cholinesterase 16.7%, 16.9%, 6.3%; p=0.007; hemoglobin 78.6%, 61.4%, 50.0%; p=0.002). CONCLUSIONS: Following Mini Nutritional Assessment, the additional measurement of albumin, cholinesterase and hemoglobin allowed a more precise grading of malnutrition. There were significant differences between the disease groups. A deficit of albumin, cholinesterase and hemoglobin was found more often in multimorbid trauma-surgical and internal patients than in neurologic psychiatric patients. PMID- 26999250 TI - Ag- and Mn-doped ZnInS/ZnS dual-emission quantum dots with zone tunability in the color coordinate. AB - In this work, we used Ag- and Mn-doped ZnInS/ZnS quantum dots (QDs) acting as a new generation of nontoxic dual-emission QDs with simultaneous tunable emission wavelengths and dual-emission ratiometric, which makes nontoxic dual-emission QDs with broad zone tunability in the color coordinate. The Ag-doped ZnInS ternary QDs can give rise to largely tunable emission wavelengths from 497 nm to 631 nm. The ratiometric of Ag and Mn dual emissions can be tuned by controlling Ag-Mn and Mn-Mn dopant coupling. With increased Mn doping amount, the increased Ag-Mn dopant coupling leads to increased Mn emission at the expense of lowered Ag emission and Ag fluorescence lifetime. The Mn-Mn coupling can be controlled by using different doping manners: co-doping Ag and Mn in ZnInS core or separate doping Ag in ZnInS core and Mn in ZnS shell. Compared with co-doping, separate doping has weaker Mn-Mn interactions, an increased Mn irradiative recombination rate constant, and bright Mn photoluminescence. PMID- 26999249 TI - The Prognostic Value of High-sensitivity C-reactive Protein and Prealbumin for Short-term Mortality in Acutely Hospitalized Multimorbid Elderly Patients: A Prospective Cohort Study. AB - OBJECTIVES: To establish the predictive value on mortality after 2 months from hospital admission of two laboratory markers of nutritional and inflammatory status, high-sensitivity C-reactive protein (hs-CRP) and prealbumin, in a cohort of frail multimorbid elderly without terminal illness. DESIGN: Prospective cohort study. SETTING: Internal medicine ward of a large teaching hospital in Italy. PARTICIPANTS: 544 Caucasian patients with acute disease consecutively admitted from January to June 2013. 102 were excluded for being younger than 65 years old, having life expectancy <30 days or not having frailty syndrome. Further 42 patients were excluded for missing data or withdrawn at follow-up. Final analysis was performed on 400 subjects (179 M, 221 F, mean age 79+/-10). MEASUREMENTS: Serum prealbumin and hs-CRP were measured at admission. Death within 2 months from hospital admission was assessed through a telephonic interview with the caregiver for each patient discharged alive. Inhospital mortality was also recorded. Survival was calculated from date of admission to our unit. RESULTS: Mean prealbumin at admission was 17.3+/-7.7 mg/dl, while hs-CRP median was 24.2 mg/L (IQR 8.7 to 51.8). 108 patients (27%) died within two months from admission. In an age- and sex-adjusted analysis, log(hs-CRP) levels at admission, but not prealbumin, were independently associated with an increased risk for mortality (HR 1.40, 95% CI 1.18 to 1.66, p<0.001). After multiple adjustments for covariates, including comorbidity burden measured through Charlson score, log(hs CRP) remained significantly associated with mortality (HR 1.38, 95% CI 1.08 to 1.76, p=0.01). A Receiver Operating Characteristic (ROC) curve was performed to test the predictive value of hs-CRP at admission on two-month mortality (AUC 0.68, 95% CI 0.63 to 0.72, p<0.001). Cut-off value was set at 38.4 mg/L. After dichotomization of hs-CRP values according to this cut-off, hs-CRP>=38.4 mg/L at admission proved to be a significant risk factor for mortality (HR 2.10, 95% CI 1.23 to 3.58, p=0.006). CONCLUSION: Serum hs-CRP, but not prealbumin, values at admission are predictors of short-term mortality at hospital admission in elderly multimorbid patients. Inflammation seems to affect prognosis more than malnutrition in this setting and may therefore guide clinicians' attitude towards therapeutic choices. PMID- 26999251 TI - 'HIV and work don't go together': Employment as a social determinant of HIV outcomes among men who have sex with men and transgender women in the Dominican Republic. AB - Men who have sex with men (MSM) and transgender women are disproportionately affected by HIV in the Dominican Republic. Little is known about their experiences living with HIV as a chronic condition. We explored employment as a social determinant of well-being with HIV. We conducted 42 qualitative in-depth interviews with MSM (n = 16) and transgender women (n = 5) living with HIV; each participant completed 2 interviews to facilitate depth and iterative analysis. We used narrative analysis and systematic coding to identify salient themes related to employment and the HIV experience and developed a conceptual model of the pathways between HIV stigma, unemployment, and HIV outcomes. Early life experiences, including rejection from families and school, resulted in limited work opportunities, especially among transgender women. Following HIV diagnosis, participants across all socio-economic levels lost jobs and/or were unable to get jobs due to illegal HIV testing and HIV stigma and discrimination. Not being able to work impacted mental health, engagement in HIV care, and overall well-being. We conclude that lack of employment is a salient concern among MSM and transgender women living with HIV. Holistic, multi-level programmes that address illegal HIV testing and discriminatory hiring practices are urgently needed to facilitate engagement in care and long-term well-being. PMID- 26999252 TI - Time Dependence of the (137)Cs Concentration in Particles Discharged from Rice Paddies to Freshwater Bodies after the Fukushima Daiichi NPP Accident. AB - The concentration of particulate (137)Cs in paddy fields, which can be a major source of (137)Cs entering the water system, was studied following the Fukushima Daiichi Nuclear Power Plant accident. To parametrize the concentration and to estimate the time dependence, paddy fields covering various levels of (137)Cs deposition were investigated over the period 2011-2013 (n = 121). The particulate (137)Cs concentration (kBq kg-SS(-1)) showed a significant correlation with the initial surface deposition density (kBq m(-2)). This suggests that the entrainment coefficient (m(2) kg-SS(-1)), defined as the ratio between the particulate (137)Cs concentration and the initial surface deposition density, is an important parameter when modeling (137)Cs wash-off from paddy fields. The entrainment coefficient decreased with time following a double exponential function. The decrease rate constant of the entrainment coefficient was clearly higher than that reported for other land uses and for river water. The difference in the decrease rates of the entrainment coefficient suggests that paddy fields play a major role in radiocesium migration through the water system. An understanding of the decrease rate of the entrainment coefficient of paddy fields is therefore crucial to understand the migration of radiocesium in the water system. PMID- 26999253 TI - Correction: Empirical Study of User Preferences Based on Rating Data of Movies. PMID- 26999254 TI - Fluorescence spectroscopy for wastewater monitoring: A review. AB - Wastewater quality is usually assessed using physical, chemical and microbiological tests, which are not suitable for online monitoring, provide unreliable results, or use hazardous chemicals. Hence, there is an urgent need to find a rapid and effective method for the evaluation of water quality in natural and engineered systems and for providing an early warning of pollution events. Fluorescence spectroscopy has been shown to be a valuable technique to characterize and monitor wastewater in surface waters for tracking sources of pollution, and in treatment works for process control and optimization. This paper reviews the current progress in applying fluorescence to assess wastewater quality. Studies have shown that, in general, wastewater presents higher fluorescence intensity compared to natural waters for the components associated with peak T (living and dead cellular material and their exudates) and peak C (microbially reprocessed organic matter). Furthermore, peak T fluorescence is significantly reduced after the biological treatment process and peak C is almost completely removed after the chlorination and reverse osmosis stages. Thus, simple fluorometers with appropriate wavelength selectivity, particularly for peaks T and C could be used for online monitoring in wastewater treatment works. This review also shows that care should be taken in any attempt to identify wastewater pollution sources due to potential overlapping fluorophores. Correlations between fluorescence intensity and water quality parameters such as biochemical oxygen demand (BOD) and total organic carbon (TOC) have been developed and dilution of samples, typically up to *10, has been shown to be useful to limit inner filter effect. It has been concluded that the following research gaps need to be filled: lack of studies on the on-line application of fluorescence spectroscopy in wastewater treatment works and lack of data processing tools suitable for rapid correction and extraction of data contained in fluorescence excitation-emission matrices (EEMs) for real-time studies. PMID- 26999255 TI - Effect of chlorination on the protein phosphatase inhibition activity for several microcystins. AB - Microcystins are of particular concern due to their toxicity to both humans and animals and may be the most prominent cyanotoxin observed in freshwater. Although a number of studies have investigated the fate of microcystins and other algal toxins through drinking water treatment facilities, measurement of their potential for toxic activity after chlorination, a popular form of treatment in the United States, has not been investigated. In this study, six microcystin variants are subjected to chlorine oxidation. The degradation of each microcystin variant is measured by liquid chromatography/mass spectrometry simultaneously with protein phosphatase inhibition (PPI) response over reaction time with chlorine. Results show that inhibition is dependent on the incorporated amino acid residues, their placement within the microcystin structure, as well as pH. This pH dependence may have practical implications to such activities such as drinking water treatment when the pH is usually adjusted to around 8. Namely, at this pH, even with chlorine addition for disinfection, PPI activity may not be totally eliminated even when the initial MYCs are eliminated. PMID- 26999256 TI - Tracing the limits of organic micropollutant removal in biological wastewater treatment. AB - Removal of organic micropollutants was investigated in 15 diverse biological reactors through short and long-term experiments. Short-term batch experiments were performed with activated sludge from three parallel sequencing batch reactors (25, 40, and 80 d solid retention time, SRT) fed with synthetic wastewater without micropollutants for one year. Despite the minimal micropollutant exposure, the synthetic wastewater sludges were able to degrade several micropollutants present in municipal wastewater. The degradation occurred immediately after spiking (1-5 MUg/L), showed no strong or systematic correlation to the sludge age, and proceeded at rates comparable to those of municipal wastewater sludges. Thus, the results from the batch experiments indicate that degradation of organic micropollutants in biological wastewater treatment is quite insensitive to SRT increases from 25 to 80 days, and not necessarily induced by exposure to micropollutants. Long-term experiments with municipal wastewater were performed to assess the potential for extended biological micropollutant removal under different redox conditions and substrate concentrations (carbon and nitrogen). A total of 31 organic micropollutants were monitored through influent-effluent sampling of twelve municipal wastewater reactors. In accordance with the results from the sludges grown on synthetic wastewater, several compounds such as bezafibrate, atenolol and acyclovir were significantly removed in the activated sludge processes fed with municipal wastewater. Complementary removal of two compounds, diuron and diclofenac, was achieved in an oxic biofilm treatment. A few aerobically persistent micropollutants such as venlafaxine, diatrizoate and tramadol were removed under anaerobic conditions, but a large number of micropollutants persisted in all biological treatments. Collectively, these results indicate that certain improvements in biological micropollutant removal can be achieved by combining different aerobic and anaerobic treatments, but that these improvements are restricted to a limited number of compounds. PMID- 26999257 TI - DNMT1 is a required genomic regulator for murine liver histogenesis and regeneration. AB - DNA methyltransferase 1 (DNMT1) is an essential regulator maintaining both epigenetic reprogramming during DNA replication and genome stability. We investigated the role of DNMT1 in the regulation of postnatal liver histogenesis under homeostasis and stress conditions. We generated Dnmt1 conditional knockout mice (Dnmt1(Deltaalb) ) by crossing Dnmt1(fl/fl) with albumin-cyclization recombination transgenic mice. Serum, liver tissues, and primary hepatocytes were collected from 1-week-old to 20-week old mice. The Dnmt1(Deltaalb) phenotype was assessed by histology, confocal and electron microscopy, biochemistry, as well as transcriptome and methylation profiling. Regenerative growth was induced by partial hepatectomy and exposure to carbon tetrachloride. The impact of Dnmt1 knockdown was also analyzed in hepatic progenitor cell lines; proliferation, apoptosis, DNA damage, and sphere formation were assessed. Dnmt1 loss in postnatal hepatocytes caused global hypomethylation, enhanced DNA damage response, and initiated a senescence state causing a progressive inability to maintain tissue homeostasis and proliferate in response to injury. The liver regenerated through activation and repopulation from progenitors due to lineage dependent differences in albumin-cyclization recombination expression, providing a basis for selection of less mature and therefore less damaged hepatic progenitor cell progeny. Consistently, efficient knockdown of Dnmt1 in cultured hepatic progenitor cells caused severe DNA damage, cell cycle arrest, senescence, and cell death. Mx1-cyclization recombination-driven deletion of Dnmt1 in adult quiescent hepatocytes did not affect liver homeostasis. CONCLUSION: These results establish the indispensable role of DNMT1-mediated epigenetic regulation in postnatal liver growth and regeneration; Dnmt1(Deltaalb) mice provide a unique experimental model to study the role of senescence and the contribution of progenitor cells to physiological and regenerative liver growth. (Hepatology 2016;64:582-598). PMID- 26999258 TI - Silk fibroin scaffold as a potential choice for female pelvic reconstruction: A study on the biocompatibility in abdominal wall, pelvic, and vagina. AB - The aim of this study was to compare the tissue reactions to silk fibroin scaffolds in the abdominal wall, vagina, and pelvic vesico-uterine of rats. Silk fibroin scaffolds were implanted subcutaneously in the abdominal, pelvic vesico uterine space, and under the vaginal mucosa of 16 rats. The animals were euthanized at 2, 4, 8, and 12 weeks postoperatively. Hematoxylin and eosin staining was performed to evaluate cellular infiltration, the percentage of macrophages and granulocytes inside and around the scaffolds. The amounts of M1/M2 macrophages at the interface of scaffolds and host tissue were evaluated through an immunofluorescence assay. The degree of acute inflammation was similar among the three groups, and lasted no more than 4 weeks. A faster ingrowth of fibroblasts was found in the abdominally implanted silk fibroin scaffolds, while vaginal implanted scaffolds committed a slower tissue ingrowth rate and much more macrophages infiltration than the pelvic and abdominal group. However, a significantly higher amount of M2 cells were seen in the three groups. In general, silk fibroin has nice biocompatibility in the abdominal, vagina, and pelvic tissue, eliciting healthy tissue formation, and might be a potential choice for female pelvic reconstruction. Microsc. Res. Tech. 80:291-297, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26999259 TI - Melatonin-Induced Nocturnal Vasodilatation Contributes to Skin Regeneration. PMID- 26999260 TI - Is intra arterial nimodipine really beneficial in vasospasm following aneurysmal subarachnoid haemorrhage? AB - Object/Background: Vasospasm is a common cause of mortality and morbidity following rupture of intracranial aneurysm. Hemodynamic therapy instituted in these patients in the past has been replaced by direct manipulation of the spastic vessels by angioplasty and intra-arterial infusion of vasodilators. However, no case control studies exist proving its superiority. The purpose of our study was to compare the efficacy of intra-arterial nimodipine (IAN) to that of hemodynamic therapy in patients with vasospasm following aSAH. MATERIAL AND METHODS: Fifty-three patients who developed vasospasm following aSAH were included in the study. IAN was instilled in addition to hemodynamic therapy in 39 patients and 14 patients (who refused to give consent for IAN) were continued on hemodynamic therapy alone and served as controls. The response to IAN was studied on angiogram. The clinical response was assessed in both the groups at regular intervals. IAN was repeated if necessary. The outcome (GOS) at discharge and at 3 months after discharge was compared. RESULTS: Thirty-six (92.3%) out of 39 patients showed immediate angiographic reversal of vasospasm.28 of them showed clinical response, of which only 11 had lasting response. 11(28.2%) of 39 patients who received IAN had a good outcome at discharge and 23(58.9%) had a favourable outcome at 3 months follow up. In those who received hemodynamic therapy alone, 4 out of 14(28.6%) patients had a good outcome at discharge and 8 (57.1%) a favourable outcome at 3 months. CONCLUSIONS: Angiographic reversal of vasospasm is seen in majority of the patients following IAN. However, this does not necessarily translate into a long lasting clinical response. The final outcome in patients who received hemodynamic therapy is comparable to those who received additional IAN. IAN does not appear to provide a major added advantage over the conventional hemodynamic therapy. PMID- 26999261 TI - Determination on the binding of thiadiazole derivative to human serum albumin: a spectroscopy and computational approach. AB - 4-[3-acetyl-5-(acetylamino)-2,3-dihydro-1,3,4-thiadiazole-2-yl]phenyl benzoate from the family of thiadiazole derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiadiazole derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance, r between the donor (HSA) and acceptor (thiadiazole derivative) was estimated according to Forster's theory of non-radiative energy transfer. The Gibbs free energy (DeltaG), enthalpy (DeltaH) and entropy (DeltaS) changes of temperature-dependent Kb was calculated, which explains that the reaction is spontaneous and exothermic. The microenvironment of HSA have also been studied using synchronous fluorescence spectroscopy, and the feature of thiadiazole derivative-induced structural changes of HSA have been carried using Fourier transform infrared spectroscopy and the Molecular modelling simulations explore the hydrophobic and hydrogen bonding interactions. PMID- 26999263 TI - More to it than meets the eye: how eye movements can elucidate the development of episodic memory. AB - The ability to recognise past events along with the contexts in which they occurred is a hallmark of episodic memory, a critical capacity. Eye movements have been shown to track veridical memory for the associations between events and their contexts (relational binding). Such eye-movement effects emerge several seconds before, or in the absence of, explicit response, and are linked to the integrity and function of the hippocampus. Drawing from research from infancy through late childhood, and by comparing to investigations from typical adults, patient populations, and animal models, it seems increasingly clear that eye movements reflect item-item, item-temporal, and item-spatial associations in developmental populations. We analyse this line of work, identify missing pieces in the literature and outline future avenues of research, in order to help elucidate the development of episodic memory. PMID- 26999262 TI - Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease. AB - IMPORTANCE: As many as 60% of patients with Parkinson disease (PD) experience psychosis, 80% develop dementia, and the use of antipsychotics (APs) in the population with PD is common. The use of APs by patients with dementia in the general population is associated with increased mortality, but whether this risk extends to patients with PD remains unknown. OBJECTIVE: To determine whether AP use in patients with PD is associated with increased mortality. DESIGN, SETTING, AND PARTICIPANTS: This retrospective matched-cohort study used data from a Veterans Health Administration database from fiscal years 1999 to 2010 to examine the risk associated with AP use in a cohort of patients with idiopathic PD and recent stable physical health. The rates of 180-day mortality were compared in 7877 patients initiating AP therapy and 7877 patients who did not initiate AP therapy (matched for age +/-2.5 years, sex, race, index year, presence and duration of dementia, PD duration, delirium, hospitalization, Charlson Comorbidity Index, and new nonpsychiatric medications). Data were analyzed from October 19, 2012, to September 21, 2015. MAIN OUTCOMES AND MEASURES: Mortality rates at 180 days in those patients who initiated AP therapy compared with matched patients who did not use APs. Cox proportional hazards regression models were used with intent-to-treat (ITT) and exposure-only analyses. RESULTS: The study population included 7877 matched pairs of patients with PD (65 women [0.8%] and 7812 men [99.2%] in each cohort; mean [SD] age, 76.3 [7.7] years for those who initiated AP therapy and 76.4 [7.6] years for those who did not). Antipsychotic use was associated with more than twice the hazard ratio (HR) of death compared with nonuse (ITT HR, 2.35; 95% CI, 2.08-2.66; P < .001). The HR was significantly higher for patients who used typical vs atypical APs (ITT HR, 1.54; 95% CI, 1.24-1.91; P < .001). Among the atypical APs used, HRs relative to nonuse of APs in descending order were 2.79 (95% CI, 1.97-3.96) for olanzapine, 2.46 (95% CI, 1.94-3.12) for risperidone, and 2.16 (95% CI, 1.88-2.48) for quetiapine fumarate. CONCLUSIONS AND RELEVANCE: Use of APs is associated with a significantly increased mortality risk in patients with PD, after adjusting for measurable confounders. This finding highlights the need for cautious use of APs in patients with PD. Future studies should examine the role of nonpharmacologic strategies in managing psychosis in PD. In addition, new pharmacologic treatments that do not increase mortality in patients with neurodegenerative diseases need to be developed. PMID- 26999264 TI - FDG PET/CT in Patients With Head and Neck Squamous Cell Carcinoma After Primary Surgical Resection With or Without Chemoradiation Therapy. AB - OBJECTIVE: The purpose of this study was to assess the value of posttreatment FDG PET/CT in patients with squamous cell carcinoma of the head and neck (HNSCC) treated with primary surgical resection with or without adjuvant concurrent chemoradiotherapy. MATERIALS AND METHODS: A total of 98 HNSCC patients were treated with primary surgical resection and had undergone PET/CT within 6 months of treatment completion. The accuracy of the scans and the added value to clinical assessment and impact on management were established based on the clinical information before and after each scan. Overall survival of patients was estimated with Kaplan-Meier curves. RESULTS: Of the total 98 scans, 25 (25.5%) were interpreted as positive and 73 (74.5%) as negative. The sensitivity of posttreatment PET/CT was 80.0%; specificity, 89.5%; positive predictive value, 66.7%; negative predictive value, 94.4%; and accuracy, 87.5%. These scans were helpful in excluding tumor in 31.8% of patients with clinical suspicion of residual disease and identifying suspected residual disease in 13.2% of patients with no prior clinical suspicion. Multivariate regression analysis showed that tumor size, grade (p = 0.041), scan type (p = 0.002), and scan result (p = 0.005) were independent covariates associated with overall survival. Kaplan-Meier analysis showed a significant difference and association in overall survival between patients with a positive versus a negative posttherapy PET/CT scan result (hazard ratio, 5.65; 95% CI, 2.48-12.83; log rank Mantel-Cox p < 0.001). CONCLUSION: Posttreatment FDG PET/CT results had a high negative predictive value, added value to clinical assessment of 35% of patients, influenced subsequent management, and were associated with survival outcome of HNSCC patients treated with primary surgical resection. PMID- 26999265 TI - Novel strategies for Plasmodium-targeted drug delivery. PMID- 26999267 TI - Sensory qualities of the phantom hand map in the residual forearm of amputees. AB - OBJECTIVE: Most amputees experience referred sensations, known as a phantom hand map, on the residual forearm, where touch on specific areas is perceived as touch on the amputated hand. The aim of this study was to evaluate the sensory qualities of the phantom hand map. METHODS: In 10 traumatic forearm-amputees touch thres-holds and discriminative touch of the phantom hand map were assessed and compared with corresponding areas on the contralateral forearm. The study assessed the localization of touch on the phantom hand map, and how distinct and similar to normal touch the referred feeling was. RESULTS: Similar touch thresholds were seen in the phantom hand map and the control site. Tactile discrimination, requiring both detection of stimulus and interpretation, was significantly better in the phantom hand map. CONCLUSION: This explorative study suggests that the phantom hand map and the superior tactile discrimination seen in the phantom hand map are based on adaptations within the brain. Further studies investigating the neural basis for the phantom hand map are needed. PMID- 26999266 TI - Bisphenol-A glucuronidation in human liver and breast: identification of UDP glucuronosyltransferases (UGTs) and influence of genetic polymorphisms. AB - 1. Bisphenol-A is a ubiquitous environmental contaminant that is primarily metabolized by glucuronidation and associated with various human diseases including breast cancer. Here we identified UDP-glucuronosyltransferases (UGTs) and genetic polymorphisms responsible for interindividual variability in bisphenol-A glucuronidation in human liver and breast. 2. Hepatic UGTs showing the highest bisphenol-A glucuronidation activity included UGT2B15 and UGT1A9. Relative activity factor normalization indicated that UGT2B15 contributes >80% of activity at bisphenol-A concentrations under 5 MUM, while UGT1A9 contributes up to 50% of activity at higher concentrations. 3. Bisphenol-A glucuronidation by liver microsomes (46 donors) ranged from 0.25 to 4.3 nmoles/min/mg protein. Two fold higher glucuronidation (p = 0.018) was observed in UGT1A9 *22/*22 livers compared with *1/*1 and *1/*22 livers. However, no associations were observed for UGT2B15*2 or UGT1A1*28 genotypes. 4. Bisphenol-A glucuronidation by breast microsomes (15 donors) ranged from <0.2 to 56 fmoles/min/mg protein. Breast mRNA expression of UGTs capable of glucuronidating bisphenol-A was highest for UGT1A1, followed by UGT2B4, UGT1A9, UGT1A10, UGT2B7 and UGT2B15. Bisphenol-A glucuronidation was over 10-fold lower in breast tissues with the UGT1A1*28 allele compared with tissues without this allele (p = 0.006). 5. UGT2B15 and UGT1A9 contribute to glucuronidation variability in liver, while UGT1A1 is important in breast. PMID- 26999269 TI - Two new lignans from the aerial part of Vitex negundo. AB - A new phenyldihydronaphthalene-type lignan, (3R,4S)-6-hydroxy-4-(4-hydroxy- 3 methoxyphenyl)-5,7-dimethoxy-3,4-dihydro-2-naphthaldehyde-3a-O-beta-d glucopyranoside (1), and a new phenylnaphthalene-type lignan, 6,7,4'-trihydroxy 3'-methoxy-2,3- cycloligna-1,4-dien-2a,3a-olide (2), along with 10-known lignan derivatives (3-12) were isolated from the aerial part of Vitex negundo var. heterophylla. Their structures were established by comprehensive 1D- and 2D-NMR spectroscopic analyses. PMID- 26999270 TI - Wells' syndrome with a clinicopathological correlation associated with mantle cell lymphoma. PMID- 26999272 TI - A practical method for the generation of organoarsenic nucleophiles towards the construction of a versatile arsenic library. AB - Nucleophilic arsenic reagents were prepared in situ from a nonvolatile cyclooligoarsine. As-As bond cleavage of the cyclooligoarsine readily proceeded with anion sources. Various kinds of organoarsenic compounds were easily constructed in high yields by selecting anion sources and electrophiles. In comparison with conventional methods of As-C bond formation, a wide variety of organoarsenic compounds were safely and easily synthesized by using this method. PMID- 26999273 TI - Influence of person- and situation-specific characteristics on collision avoidance behavior in human locomotion. AB - In everyday situations, pedestrians deploy successful strategies to avoid collisions with other persons crossing their paths. In this study, 2 experiments were conducted to investigate to what extent personal or situational characteristics affect role attribution and contribution to successful collision avoidance in human locomotion. Pairs of subjects walked at their natural speed from a start to a goal point. Walking paths were defined in such a way that subjects would collide halfway on their trajectory, if they did not actively avoid colliding by speed or path adjustments. In the first experiment, we investigated whether crossing order, path, and speed adjustments correlate with subject-specific parameters, such as gender, height, and personality traits. It is interesting that individuals' collision avoidance behavior was not correlated with any of these factors. In the second experiment, initial walking speed and heading were used to predict the crossing order. It was found that these 2 parameters are sufficient to estimate future role attribution with 95% confidence already 2.5 m before the crossing; that is, even before any collision avoidance behavior is initiated. In sum, this suggests that collision avoidance strategies in human locomotion are based on situational rather than on personal characteristics. These situational characteristics result in role attributions, which are highly predictable within and across pairs of pedestrians, whereby the role-dependent contribution of the pedestrian giving way is of greater relevance for successful collision avoidance. (PsycINFO Database Record PMID- 26999271 TI - The Impact of High-Frequency Chest Wall Oscillation on Healthcare Use in Patients with Neuromuscular Diseases. AB - RATIONALE: People with neuromuscular disease frequently have difficulty clearing pulmonary secretions, which leads to pneumonia and respiratory failure. High frequency chest wall oscillation (HFCWO) is one intervention used to facilitate secretion clearance. OBJECTIVES: The objective of this study was to determine if HFCWO therapy leads to improved outcomes as measured by lower healthcare use for patients who have a chronic neuromuscular disease. METHODS: We performed a cohort study comparing healthcare claims before and after initiation of HFCWO. Data were obtained from two large databases of commercial insurance claims. Study subjects were commercial insurance members with an International Classification of Diseases, Ninth Revision, code for a neuromuscular disease and a claim for HFCWO between 2007 and 2011. The study included both children and adults. MEASUREMENTS AND MAIN RESULTS: There were 426 patients in this study. Their mean age was 29.9 +/- 22 years. Total medical costs per member per month decreased by $1,949 (18.6%) after initiation of HFCWO (P = 0.002). Inpatient admission costs decreased by $2,392 (41.7%) (P = 0.001), and pneumonia costs decreased by $514 (18.1%) (P = 0.015). To account for the possibilities of misclassification based on diagnosis and bias due to loss to follow-up, we compared outcomes between those lost to follow-up and those not, and we found similar results. CONCLUSIONS: Total medical costs, hospitalizations, and pneumonia claims were less after than before initiation of HFCWO in a broad group of patients with neuromuscular disease. Subject to the limitations that administrative data did not capture how HFCWO was used and that HFCWO may be a marker of generally better care, our findings lend support to the routine use of this intervention in the care of patients with neuromuscular diseases. PMID- 26999277 TI - Chemotherapy is of Value in Second Line and Beyond, Relapsed High-grade, Serous Epithelial Ovarian Cancer: An Analysis of Outcomes Obtained With Oral Etoposide. AB - BACKGROUND: Epithelial ovarian cancer is chemotherapy responsive, and multiple lines of chemotherapy are often given. However, there are few data with regard to its effectiveness in later lines. Our aim was to assess its benefit in the high grade, serous subtype relative to the line of therapy, using etoposide as the example. METHODS: Women treated with oral etoposide at the British Columbia Cancer Agency upon recurrence/progression in the years 2000 to 2010 were reviewed. Kaplan-Meier and Cox regression methods were used to correlate line of therapy with overall survival, progression-free survival, and interval between etoposide initiation and next progression or death (EPFS). RESULTS: A total of 219 women, median age 61, received etoposide as second (17%), third (30%), fourth (26%), fifth (17%), and sixth to eighth (11%) lines of therapy. The median number of cycles was 2 to 4. Patients who received etoposide as fourth-line to eighth line treatment had a significantly longer median overall survival and initial progression-free survival (from diagnosis to first relapse) when compared with those who received it as second-line to third-line treatment (47.8 vs. 25.8 mo, P<0.0001; and 16.1 vs. 12.1 mo, P<0.0001, respectively); that is, a selected population of survivors received it later in the course of their disease. On univariate analysis, there was no significant difference in median EPFS (range, 2 to 2.9 mo) on the basis of line of therapy. On multivariate analysis, the hazard ratios improved through the third, fourth, and fifth lines (hazard ratios: 0.82, 0.77, and 0.34, respectively), and was statistically significant in the fifth line. The a priori-defined endpoint of clinical benefit was the "percentage not progressing at 3 months," and this was achieved in 32% to 48%. CONCLUSIONS: In this retrospective study, a similar degree of benefit from etoposide, as defined by the percentage remaining progression free at 3 months, was seen in all lines of therapy. PMID- 26999274 TI - Shape-Related Toxicity of Titanium Dioxide Nanofibres. AB - Titanium dioxide (TiO2) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO2 nanoparticles have been extensively studied, the toxicological characterization of TiO2 nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially available anatase TiO2 nanofibres using TiO2 nanoparticles (NP) and crocidolite asbestos as non-fibrous or fibrous benchmark materials. The evaluated endpoints were cell viability, haemolysis, macrophage activation, trans-epithelial electrical resistance (an indicator of the epithelial barrier competence), ROS production and oxidative stress as well as the morphology of exposed cells. The results showed that TiO2 nanofibres caused a cell-specific, dose-dependent decrease of cell viability, with larger effects on alveolar epithelial cells than on macrophages. The observed effects were comparable to those of crocidolite, while TiO2 NP did not decrease cell viability. TiO2 nanofibres were also found endowed with a marked haemolytic activity, at levels significantly higher than those observed with TiO2 nanoparticles or crocidolite. Moreover, TiO2 nanofibres and crocidolite, but not TiO2 nanoparticles, caused a significant decrease of the trans-epithelial electrical resistance of airway cell monolayers. SEM images demonstrated that the interaction with nanofibres and crocidolite caused cell shape perturbation with the longest fibres incompletely or not phagocytosed. The expression of several pro-inflammatory markers, such as NO production and the induction of Nos2 and Ptgs2, was significantly increased by TiO2 nanofibres, as well as by TiO2 nanoparticles and crocidolite. This study indicates that TiO2 nanofibres had significant toxic effects and, for most endpoints with the exception of pro inflammatory changes, are more bio-active than TiO2 nanoparticles, showing the relevance of shape in determining the toxicity of nanomaterials. Given that several toxic effects of TiO2 nanofibres appear comparable to those observed with crocidolite, the possibility that they exert length dependent toxicity in vivo seems worthy of further investigation. PMID- 26999276 TI - Molecular Electrostatic Potentials from Invariom Point Charges. AB - A set of look-up point charges for generating molecular electrostatic potentials is provided. The set relies on atom classification of the invariom database, which has already been applied to assign aspherical scattering factors in single crystal X-ray diffraction. The focus of the investigation is on improving the accuracy of electrostatic potentials calculated by using tabulated point charges. In this respect, the performance of invariom point charges is compared with 1) those from a restrained fit to the electrostatic potential directly following quantum-chemical DFT computations, 2) semi-empirical AM1-bcc charges, and 3) conceptually similar TPACM4 look-up charges. Invariom classification gives charges that perform better than those from TPACM4, although tabulated charges remain inferior to those from molecule-specific computations. Point-charge electrostatic potentials also agree favorably with those from charge-density studies on the basis of X-ray experiments, without requiring the considerable effort of the latter. PMID- 26999275 TI - Capping beta-hairpin with N-terminal d-amino acid stabilizes peptide scaffold. AB - Various strategies exist to stabilize de novo designed synthetic peptide beta hairpins or beta-sheets structures, especially at the non-hydrogen bonding position. However, strategies to stabilize strand termini, which are affected by fraying, are highly limited. Here, by substituting N-terminal aliphatic amino acid with its mirror image counterpart, we achieve a significant increase in scaffold stabilization, resulting from the formation of a terminal aliphatic aromatic hydrophobic C?H...pi cluster. Our extensive solution NMR studies support the incorporation of an N-terminal d-aliphatic amino acid in the design of short beta-hairpins, while successfully retaining the overall structural scaffold. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 260-266, 2016. PMID- 26999278 TI - Patterns of Species Richness and Turnover for the South American Rodent Fauna. AB - Understanding the spatial distribution of species sheds light on the group's biogeographical history, offers clues to the drivers of diversity, and helps to guide conservation strategies. Here, we compile geographic range information for South America's diverse rodents, whose 14 families comprise ~50% of the continent's mammalian species. The South American rodent fauna is dominated by independent and temporally staggered radiations of caviomorph and sigmodontine groups. We mapped species richness and turnover of all rodents and the principal clades to identify the main predictors of diversity patterns. Species richness was highest in the Andes, with a secondary hotspot in Atlantic Forest and some regions of considerable richness in Amazonia. Differences in richness were evident between the caviomorphs and sigmodontines, the former showing the greatest richness in tropical forests whereas the latter show-and largely determine-the all-rodent pattern. Elevation was the main predictor of sigmodontine richness, whereas temperature was the principal variable correlated with richness of caviomorphs. Across clades, species turnover was highest along the Andes and was best explained by elevational relief. In South America, the effects of the familiar latitudinal gradient in species richness are mixed with a strong longitudinal effect, triggered by the importance of elevation and the position of the Andes. Both latitudinal and elevational effects help explain the complicated distribution of rodent diversity across the continent. The continent's restricted-range species-those seemingly most vulnerable to localized disturbance-are mostly distributed along the Andes and in Atlantic Forest, with the greatest concentration in Ecuador. Both the Andes and Atlantic Forest are known hotspots for other faunal and floral components. Contrasting patterns of the older caviomorph and younger sigmodontine radiations underscore the interplay of both historical and ecological factors in determining present-day diversity patterns. PMID- 26999279 TI - Relationships between p14ARF Gene Methylation and Clinicopathological Features of Colorectal Cancer: A Meta-Analysis. AB - We conducted a meta-analysis to explore the relationships between p14ARF gene methylation and clinicopathological features of colorectal cancer (CRC). Databases, including Pubmed, Embase and Cochrane Library, were searched and, finally, a total of 18 eligible researches encompassing 1988 CRC patients were selected. Combined odds ratios (ORs) with 95% confidence intervals (95% CIs) were evaluated under a fixed effects model for absence of heterogeneity. Significant associations were observed between p14ARF gene methylation and tumor location (OR = 2.35, 95% CI: 1.55-3.55, P = 0.001), microsatellite instability (MSI) status (OR = 3.28, 95% CI: 2.12-5.07, P<0.0001). However, there were no significant associations between p14ARF gene methylation and tumor stage, tumor differentiation. We concluded that p14ARF gene methylation may be significantly associated with tumor location, and MSI status of CRC. PMID- 26999284 TI - Electric-Field Induced Activation of Dark Excitonic States in Carbon Nanotubes. AB - Electrical activation of optical transitions to parity-forbidden dark excitonic states in individual carbon nanotubes is reported. We examine electric-field effects on various excitonic states by simultaneously measuring photocurrent and photoluminescence. As the applied field increases, we observe an emergence of new absorption peaks in the excitation spectra. From the diameter dependence of the energy separation between the new peaks and the ground state of E11 excitons, we attribute the peaks to the dark excited states which became optically active due to the applied field. Field-induced exciton dissociation can explain the photocurrent threshold field, and the edge of the E11 continuum states has been identified by extrapolating to zero threshold. PMID- 26999283 TI - Affective systems induce formal thought disorder in early-stage psychosis. AB - Although formal thought disorder (FTD) has been described since early conceptualizations of psychosis, its underlying mechanisms are unclear. Evidence suggests FTD may be influenced by affective and cognitive systems; however, few have examined these relationships-with none focusing on early-stage psychosis (EP). In this study, positive FTD and speech production were measured in sex- and race-matched EP (n = 19) and healthy control (n = 19) groups by assessing "reactivity"-a change in experimental compared with baseline conditions-across baseline, affective, and cognitive conditions. Relationships with functioning were also examined within each group. Three key findings emerged: (a) the EP group displayed large differences in positive FTD and speech production, (b) those with EP exhibited affective reactivity for positive FTD, and (c) positive FTD and affective reactivity were linked with poor real-world functioning in EP and these relationships did not considerably change when controlling for positive symptom (e.g., delusions, hallucinations) severity. Our findings provide preliminary evidence that affective, but not cognitive, systems play a critical role in positive FTD. Affective reactivity, in particular, may aid in predicting those with EP who go on to develop serious social impairments. Future work should focus on whether affective systems differentially influence those at separate points on the psychosis-spectrum in an effort to establish evidence-based treatments for FTD. (PsycINFO Database Record PMID- 26999280 TI - The Positive and Negative Syndrome Scale (PANSS): A Three-Factor Model of Psychopathology in Marginally Housed Persons with Substance Dependence and Psychiatric Illness. AB - Rates of psychopathology are elevated in marginalized and unstably housed persons, underscoring the need for applicable clinical measures for these populations. The Positive and Negative Syndrome Scale (PANSS) is a clinical instrument principally developed for use in schizophrenia to identify the presence and severity of psychopathology symptoms. The current study investigates whether a reliable and valid PANSS factor structure emerges in a marginally housed, heterogeneous sample recruited from the Downtown Eastside of Vancouver where substance use disorders and psychiatric illness are pervasive. Participants (n = 270) underwent structured clinical assessments including the PANSS and then were randomly assigned to either exploratory (EFA) or confirmatory factor analytic (CFA) subsamples. EFA pointed to a novel three factor PANSS. This solution was supported by CFA. All retained items (28 out of 30) load significantly upon hypothesized factors and model goodness of fit analyses are in the acceptable to good range. Each of the three first-order factor constructs, labeled Psychosis/Disorganized, Negative Symptoms/Hostility, and Insight/Awareness, contributed significantly to measurement of a higher-order psychopathology construct. Further, the latent structure of this 3-factor solution appears temporally consistent over one-year. This PANSS factor structure appears valid and reliable for use in persons with multimorbidity, including substance use disorders. The structure is somewhat distinct from existing solutions likely due to the unique characteristics of this marginally housed sample. PMID- 26999285 TI - A Generic Individual-Based Spatially Explicit Model as a Novel Tool for Investigating Insect-Plant Interactions: A Case Study of the Behavioural Ecology of Frugivorous Tephritidae. AB - Computational modelling of mechanisms underlying processes in the real world can be of great value in understanding complex biological behaviours. Uptake in general biology and ecology has been rapid. However, it often requires specific data sets that are overly costly in time and resources to collect. The aim of the current study was to test whether a generic behavioural ecology model constructed using published data could give realistic outputs for individual species. An individual-based model was developed using the Pattern-Oriented Modelling (POM) strategy and protocol, based on behavioural rules associated with insect movement choices. Frugivorous Tephritidae (fruit flies) were chosen because of economic significance in global agriculture and the multiple published data sets available for a range of species. The Queensland fruit fly (Qfly), Bactrocera tryoni, was identified as a suitable individual species for testing. Plant canopies with modified architecture were used to run predictive simulations. A field study was then conducted to validate our model predictions on how plant architecture affects fruit flies' behaviours. Characteristics of plant architecture such as different shapes, e.g., closed-canopy and vase-shaped, affected fly movement patterns and time spent on host fruit. The number of visits to host fruit also differed between the edge and centre in closed-canopy plants. Compared to plant architecture, host fruit has less contribution to effects on flies' movement patterns. The results from this model, combined with our field study and published empirical data suggest that placing fly traps in the upper canopy at the edge should work best. Such a modelling approach allows rapid testing of ideas about organismal interactions with environmental substrates in silico rather than in vivo, to generate new perspectives. Using published data provides a saving in time and resources. Adjustments for specific questions can be achieved by refinement of parameters based on targeted experiments. PMID- 26999282 TI - Negative symptoms are associated with an increased subjective cost of cognitive effort. AB - Motivational deficits in schizophrenia are proposed to be attributable in part to abnormal effort-cost computations. Inflated subjective cognitive effort costs may explain diminished functioning in schizophrenia to the extent that they drive avoidance of complex decision-making and planning. Although previous data support inflated subjective physical effort costs for individuals with schizophrenia, evidence on cognitive effort is mixed. We exploited the methodological advantages of a recently developed cognitive effort-discounting paradigm (Westbrook, Kester, & Braver, 2013) to examine effort-cost computations in schizophrenia. The paradigm quantifies subjective costs in terms of explicit, continuous discounting of monetary rewards based on parametrically varied demands (levels N of the N back working memory task), holding objective features of task duration and reward likelihood constant. Both healthy participants (N = 25) and schizophrenia patients (N = 25) showed systematic influences of reward and task demands on choice patterns. Critically, however, participants with schizophrenia discounted rewards more steeply as a function of effort, indicating that effort was more costly for this group. Moreover, discounting varied robustly with symptomatology, such that schizophrenia patients with greater clinically rated negative symptom severity discounted rewards more steeply. These findings extend the current literature on abnormal-effort cost computations in schizophrenia by establishing a clear relationship between the costliness of cognitive effort and negative symptoms. (PsycINFO Database Record PMID- 26999286 TI - Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature. AB - INTRODUCTION: Studies have reported associations between serum anticholinergic activity (SAA) and decline in cognitive performance, delirium, and functional impairment. The aim of this meta-analysis was to explore and quantify associations between SAA and adverse cognitive and functional outcomes in older people. MATERIALS AND METHODS: A literature search in Ovid MEDLINE, EMBASE, PsycINFO and IPA from 1946-2014 was completed. The primary outcomes of interest were cognitive and functional adverse outcomes associated with SAA in older people aged 55 years and above. The Cochrane Risk-Bias assessment tool was used to assess bias in randomised controlled trials (RCTs). The Newcastle-Ottawa Scale was used to assess the quality of non-RCTs. Meta-analyses were conducted for RCTs and cohort studies separately. Heterogeneity was assessed using I2 tests. RESULTS: The primary electronic literature search identified a total of 1559 records in the 4 different databases. On the basis of full-text analysis, 33 studies that met the inclusion criteria. The review included 4 RCTs, 5 prospective cohort studies, 3 longitudinal cohort studies, 17 cross-sectional studies, and 4 case-control studies. Twenty-four of the retrieved studies examined an association between SAA and cognitive outcomes, 2 studies examined an association with SAA and functional outcomes and 8 studies examined associations between SAA and both cognitive, and functional outcomes. The meta-analysis on 4 RCTs showed no association with higher SAA and cognitive performance (I2 = 89.38%, H2 = 25.53 and p-value = <0.05) however, the pooled data from 4 observational studies showed elevated SAA was associated with reduced cognitive performance (I2 = 0.00%, H2 = 3.37 and p-value = 0.34). CONCLUSION: This systematic review summarises the limitations of the SAA on predicting cognitive and functional outcomes in older people. SAA measured by receptor bioassay is flawed and its use in older people with multimorbidity and polypharmacy is questionable. PMID- 26999288 TI - Correction: Evaluation in Cameroon of a Novel, Simplified Methodology to Assist Molecular Microbiological Analysis of V. cholerae in Resource-Limited Settings. PMID- 26999287 TI - Interfacial Engineering for Enhanced Light Absorption and Charge Transfer of a Solution-Processed Bulk Heterojunction Based on Heptazole as a Small Molecule Type of Donor. AB - In the present study, a solution-processed organic semiconductor based on indolocarbazole derivative (heptazole) is introduced as a p-type donor material for a bulk-heterojunction photovoltaic device. The heptazole has an optical band gap of 2.97 eV, and its highest occupied molecular orbital-lowest unoccupied molecular orbital energy levels are compactable with the PC60BM to construct a donor-acceptor heterojuction for energy harvesting and transfer. When the bulk heterojunction photovoltaic devices consisting of ITO/PEDOT:PSS/heptazole:PC60BM/Al with different blending ratio of heptazole:PC60BM were constructed, the cell with 1:1 blending ratio exhibited the best power conversion efficiency. Further, when an indoline organic dye (D149) was introduced as an interfacial modifier to the above donor/acceptor bulk heterojunction, the device demonstrated an enhanced overall power conversion efficiency from 1.26% to 2.51% hence demonstrating enhancement by the factor of 100%. The device was further characterized using electronic absorption spectroscopy, photoluminescence spectroscopy, electrochemical impedance spectroscopy, and the photovoltage decay kinetics. These studies reveal that the enhanced power conversion efficiency of the device is due to the enhanced charge transfer with the complementary light absorption feature of the interfacial D149 dye molecules. PMID- 26999289 TI - Effects of Game Location, Quality of Opposition, and Starting Quarter Score in the Outcome of Elite Water Polo Quarters. AB - The notational analysis is used to investigate teams' performance in water polo, especially focused on the determinants of success. Recently, a new topic has emerged "the situational variables," which includes the game conditions that may influence the performance at a behavioral level. The aim of this study was to identify the interactive effects of starting quarter score (SQS) (i.e., score difference at the beginning of each quarter and at the final score) and game location (GL) (i.e., home and away teams) in relation to quality of opposition (i.e., positions of difference between opposing teams at the end-of-season rankings) in elite men's water polo games. Data comprised 528 games (n = 2,112 quarters) from the first Spanish water polo division. A linear regression analysis was applied to show the impact of SQS and GL in relation to quality of opposition (unbalanced and balanced) for quarter (all quarters, and second, third, and fourth quarters). Results showed that SQS has an important effect for all quarters (0.16) and for the second (0.14) and third (0.14) quarters in balanced games (whereas the fourth quarter has an unpredictable outcome), and for each quarter (all quarters: 0.33; second quarter: 0.55; third quarter: 0.44; fourth quarter: 0.26) in unbalanced games. In addition, GL effects emerged for balanced (0.31) and unbalanced (0.45) games for all quarters and specifically for the second quarter of the unbalanced games. Therefore, this study showed that the elite water polo game dynamics, indirectly providing a reference for coaches (i.e., effective tactical approach) and physical trainers (i.e., high performance intensities), plans to improve their players' performance. PMID- 26999290 TI - The more things change, the more things stay the same: maternal attitudes 3 to 18 months postpartum. AB - AIM: Becoming a parent precipitates changes in new mothers' psychological and social domains. Previous literature has focused exclusively on pregnancy and the early postpartum, but parenting is an evolving process, necessitating adaption to changing circumstances. We extended previous literature and investigate the changes in the postpartum from 3 to 18 months that occur in maternal attitudes. METHODS: Using the Childbearing Attitudes Questionnaire, we collected data on mothers' ratings of maternal worries, self-efficacy, mother-infant bonding, relationship with the partner and interest in sex (n = 171 women). Data were analysed with a latent growth curve. RESULTS: Results demonstrated stability in all maternal attitudes after 3 months postpartum. Further, different maternal attitudes are affected by different variables. Maternal worries and self-efficacy are associated with parity, postpartum depression and child temperament. Interestingly, a negative evaluation of the relationship with the partner was only associated with breastfeeding status, while interest in sex was associated with parity, socio-economic status (SES) and depressive symptoms. CONCLUSION: Despite general stability, different maternal attitudes related to different sets of variables. These patterns of attitudes in relation to relevant variables are discussed in terms of the literature on self-efficacy and gender roles, with important implications for clinical interventions. PMID- 26999291 TI - In Situ Transformation of Chitosan Films into Microtubular Structures on the Surface of Nanoengineered Titanium Implants. AB - There is considerable interest in combining bioactive polymers such as chitosan with titanium bone implants to promote bone healing and address therapeutic needs. However, the fate of these biodegradable polymers especially on titanium implants is not fully explored. Here we report in situ formation of chitosan microtube (CMT) structures from chitosan films on the implant surface with titania nanotubes (TNTs) layer, based on phosphate buffer-induced transformation and precipitation process. We have comprehensively analyzed this phenomenon and the factors that influence CMT formation, including substrate topography, immersion solution and its pH, effect of coating thickness, and time of immersion. Significance of reported in situ formation of chitosan microtubes on the TNTs surface is possibly to tailor properties of implants with favorable micro and nano morphology using a self-ordering process after the implant's insertion. PMID- 26999292 TI - Pre- and Post-Natal Stress Programming: Developmental Exposure to Glucocorticoids Causes Long-Term Brain-Region Specific Changes to Transcriptome in the Precocial Japanese Quail. AB - Exposure to stress during early development can permanently influence an individual's physiology and behaviour, and affect its subsequent health. The extent to which elevated glucocorticoids cause such long-term 'programming' remains largely untested. In the present study, using the Japanese quail as our study species, we independently manipulated exposure to corticosterone during pre and/or post-natal development and investigated the subsequent effects on global gene expression profiles within the hippocampus and hypothalamus upon achieving adulthood. Our results showed that the changes in transcriptome profiles in response to corticosterone exposure clearly differed between the hippocampus and the hypothalamus. We also showed that these effects depended on the developmental timing of exposure and identified brain-region specific gene expression patterns that were either: (i) similarly altered by corticosterone regardless of the developmental stage in which hormonal exposure occurred or (ii) specifically and uniquely altered by either pre-natal or post-natal exposure to corticosterone. Corticosterone-treated birds showed alterations in networks of genes that included known markers of the programming actions of early-life adversity (e.g. brain-derived neurotrophic factor and mineralocorticoid receptor within the hippocampus; corticotrophin-releasing hormone and serotonin receptors in the hypothalamus). Altogether, for the first time, these findings provide experimental support for the hypothesis that exposure to elevated glucocorticoids during development may be a key hormonal signalling pathway through which the long-term phenotypic effects associated with early-life adversity emerge and potentially persist throughout the lifespan. These data also highlight that stressors might have different long-lasting impacts on the brain transcriptome depending on the developmental stage in which they are experienced; more work is now required to relate these mechanisms to organismal phenotypic differences. PMID- 26999294 TI - College Students' Responses to Suicidal Content on Social Networking Sites: An Examination Using a Simulated Facebook Newsfeed. AB - Although Facebook has a peer-initiated suicide prevention protocol, little is known about users' abilities to notice, recognize, and appropriately interpret suicidal content or about their willingness to intervene. In this study, 468 college students were randomly assigned to interact with a simulated Facebook newsfeed containing content reflecting various suicide risk levels. A larger proportion of those exposed to content reflecting moderate and severe suicide risk noticed, recognized, appropriately interpreted, and endorsed taking action to intervene, as compared to those exposed to content representing no or low risk. Overall, results indicate that college students are responsive to suicidal content on Facebook. PMID- 26999293 TI - Translational atherosclerosis research: From experimental models to coronary artery disease in humans. AB - Atherosclerosis is the leading cause of death worldwide. Research on the pathophysiological mechanisms of atherogenesis has made tremendous progress over the past two decades. However, despite great advances there is still a lack of therapies that reduce adverse cardiovascular events to an acceptable degree. This review addresses successes, but also questions, challenges, and chances regarding the translation of basic science results into clinical practice, i.e. the capability to apply the results of basic and/or clinical research in order to design therapies suitable to improve patient outcome. Specifically, it discusses problems in translating findings from the most broadly used murine models of atherosclerosis into clinically feasible therapies and strategies potentially improving the results of clinical trials. Most likely, the key to success will be a multimodal approach employing novel imaging methods as well as large scale screening tools-summarized as "omics" approach. Using individually tailored therapies, plaque stabilization and regression could prevent adverse cardiovascular events thereby improving outcome of a large number of patients. PMID- 26999295 TI - Catalyst Self-Assembly for Scalable Patterning of Sub 10 nm Ultrahigh Aspect Ratio Nanopores in Silicon. AB - Nanoporous silicon (NPSi) has received significant attention for its potential to contribute to a large number of applications, but has not yet been extensively implemented because of the inability of current state-of-the-art nanofabrication techniques to achieve sufficiently small pore size, high aspect ratio, and process scalability. In this work we describe the fabrication of NPSi via a modified metal-assisted chemical etching (MACE) process in which silica-shell gold nanoparticle (SiO2-AuNP) monolayers self-assemble from solution onto a silicon substrate. Exposure to the MACE etchant solution results in the rapid consumption of the SiO2 spacer shell, leaving well-spaced arrays of bare AuNPs on the substrate surface. Particles then begin to catalyze the etching of nanopore arrays without interruption, resulting in the formation of highly anisotropic individual pores. The excellent directionality of pore formation is thought to be promoted by the homogeneous interparticle spacing of the gold core nanocatalysts, which allow for even hole injection and subsequent etching along preferred crystallographic orientations. Electron microscopy and image analysis confirm the ability of the developed technique to produce micrometer-scale arrays of sub 10 nm nanopores with narrow size distributions and aspect ratios of over 100:1. By introducing a scalable process for obtaining high aspect ratio pores in a novel size regime, this work opens the door to implementation of NPSi in numerous devices and applications. PMID- 26999296 TI - EGFR: stopping stathmin to start the cycle. PMID- 26999297 TI - Enhanced Efficacy of Artemisinin Loaded in Transferrin-Conjugated Liposomes versus Stealth Liposomes against HCT-8 Colon Cancer Cells. AB - Artemisinin (ART) is a unique sesquiterpene lactone isolated from Artemisia annua that is well known for antimalarial properties and was recently reported as a promising anticancer drug. The aim of our work was to develop a novel nanocarrier for enhanced ART delivery and activation in cancer tissues, because transferrin receptors are largely expressed in cancer cells and the iron content is higher than in normal cells. ART was loaded in transferrin-conjugated liposomes (ART-L Tf), and the performance was compared with ART loaded in stealth liposomes (ART L). All of the liposomes were fully characterized in terms of size, drug entrapment efficiency, transferrin coupling moieties, and stability. Both cell uptake and cytotoxicity studies of the developed nanocarriers were tested in the HCT-8 cell line, selected among several cell lines because of transferrin receptor overexpression. The results confirmed the enhanced delivery of ART-L-Tf in comparison with ART-L in the targeting of the HCT-8 cell line and an improved cytotoxicity as a result of the presence of iron ions, which resulted in concomitant synergism derived from the increased expression of transferrin receptors on the surface of the tumor cells. PMID- 26999298 TI - Viewing humans as molecules to improve accuracy of clinical predictions. PMID- 26999299 TI - Smoking, Binge Drinking, and Drug Use Among Childhood Cancer Survivors: A Meta Analysis. AB - INTRODUCTION: Childhood cancer survivors are at risk for late effects of therapy, some of which may be exacerbated by smoking, alcohol, or drug use. We undertook a meta-analysis of the literature to determine whether survivors engage in risk taking behaviors at rates different from their peers/siblings. METHODS: Studies comparing current engagement in risk-taking behaviors between cancer survivors and siblings or matched peers were identified in MEDLINE (1946-), EMBASE (1947-), PsychINFO (1806-), and the Cochrane Controlled Trials Register. Two reviewers assessed publications for inclusion and extracted data independently. Studies were combined using inverse variance weighting to determine odds ratios (OR) and prevalence rates of risk-taking behaviors in survivors compared to controls. RESULTS: Fourteen of 1,713 studies satisfied inclusion criteria. Twelve assessed smoking, six binge drinking, and seven drug use. Among survivors, 22% (95% confidence interval 0.19, 0.26) smoked, 20% (0.08, 0.51) were binge drinkers, and 15% (0.10, 0.23) used drugs. Survivors were less likely than siblings to smoke (OR 0.68 [0.49, 0.96]) or binge drink (OR 0.77 [0.68, 0.88]), but similarly likely to use drugs (OR 0.33 [0.03, 3.28]). Survivors were less likely than matched peers to smoke (OR 0.54 [0.42, 0.70]) or use drugs (OR 0.57 [0.40, 0.82]), but equally likely to binge drink (OR 0.97 [0.38, 2.49]). CONCLUSIONS: Childhood cancer survivors engage in similar or lower rates of risk taking than their siblings/peers. Future studies should identify survivors most likely to benefit from focused interventions, and determine the impact of risk-taking behaviors on the risk for late effects of cancer therapy. PMID- 26999300 TI - Adolescent experience affects postnatal ultrasonic vocalizations and gene expression in future offspring. AB - The present study measured postnatal ultrasonic vocalization (USV) and gene expression to examine potential changes in communication and/or attachment in the offspring of mothers exposed to morphine during adolescence. Offspring of morphine-exposed (Mor-F1), saline-exposed (Sal-F1), or non-handled control (Con F1) female Sprague-Dawley rats were tested for separation-induced distress calls and maternal potentiation of distress calls during early postnatal development. We also examined relative expression of dopamine D2 receptor and mu opioid receptor (oprm1) mRNA in the nucleus accumbens and hypothalamus in these offspring, as their activity has been implicated in the regulation of postnatal USV in response to maternal separation. The findings indicate that adolescent experiences of future mothers, including their 10 daily saline or morphine injections, can result in significant region-specific differences in gene expression. In addition, these experiences resulted in fewer numbers of separation-induced distress calls produced by offspring. In contrast, augmented maternal potentiation was only observed in Mor-F1 offspring. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:714-723, 2016. PMID- 26999301 TI - A comprehensive assessment of the association between anemia, clinical covariates and outcomes in a population-wide heart failure registry. AB - BACKGROUND: The aim was to investigate the prevalence of, predictors of, and association with mortality and morbidity of anemia in a large unselected cohort of patients with heart failure (HF) and reduced ejection fraction (HFrEF) and to explore if there were specific subgroups of high risk. METHODS: In patients with HFrEF in the Swedish Heart Failure Registry, we assessed hemoglobin levels and associations between baseline characteristics and anemia with logistic regression. Using propensity scores for anemia, we assessed the association between anemia and outcomes with Cox regression, and performed interaction and sub-group analyses. RESULTS: There were 24,511 patients with HFrEF (8303 with anemia). Most important independent predictors of anemia were higher age, male gender and renal dysfunction. One-year survival was 75% with anemia vs. 81% without (p < 0.001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all-cause death 1.34 (1.28-1.40; p < 0.0001), CV mortality 1.28 (1.20-1.36; p < 0.0001), and combined CV mortality or HF hospitalization 1.24 (1.18-1.30; p < 0.0001). In interaction analyses, anemia was associated with greater risk with lower age, male gender, EF 30-39%, and NYHA class I-II. CONCLUSION: In HFrEF, anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity. The influence of anemia on mortality was significantly greater in younger patients, in men, and in those with more stable HF. The clinical implication of these findings might be in the future to perform targeted treatment studies. PMID- 26999302 TI - Structure of the Human Protein Kinase ZAK in Complex with Vemurafenib. AB - The mixed lineage kinase ZAK is a key regulator of the MAPK pathway mediating cell survival and inflammatory response. ZAK is targeted by several clinically approved kinase inhibitors, and inhibition of ZAK has been reported to protect from doxorubicin-induced cardiomyopathy. On the other hand, unintended targeting of ZAK has been linked to severe adverse effects such as the development of cutaneous squamous cell carcinoma. Therefore, both specific inhibitors of ZAK, as well as anticancer drugs lacking off-target activity against ZAK, may provide therapeutic benefit. Here, we report the first crystal structure of ZAK in complex with the B-RAF inhibitor vemurafenib. The cocrystal structure displayed a number of ZAK-specific features including a highly distorted P loop conformation enabling rational inhibitor design. Positional scanning peptide library analysis revealed a unique substrate specificity of the ZAK kinase including unprecedented preferences for histidine residues at positions -1 and +2 relative to the phosphoacceptor site. In addition, we screened a library of clinical kinase inhibitors identifying several inhibitors that potently inhibit ZAK, demonstrating that this kinase is commonly mistargeted by currently used anticancer drugs. PMID- 26999303 TI - Provision of an on-call service for regional anaesthesia. PMID- 26999304 TI - Nickel-Catalyzed Regioselective Cleavage of C(sp(2))-S Bonds: Method for the Synthesis of Tri- and Tetrasubstituted Alkenes. AB - We describe here an efficient route for the synthesis of (Z)-vinylic sulfides 3 via the highly regio- and stereoselective coupling of (Z)-1,2 bis(aryl(alkyl)thio)alkenes and Grignard reagents over a Ni catalyst under mild conditions. (Z)-Vinylic sulfides 3 are important intermediates in the synthesis of tri- and tetrasubstituted alkenes that are important construction blocks for drugs and natural products. The directing organosulfur groups (SR) can be converted to diaryl(alkyl) disulfides (RSSR) using H2O2 as oxidant, hence avoiding the waste of sulfur resources. The protocol provides a general method that is highly regio- and stereoselective for the synthesis of a diversity of tri and tetrasubstituted alkenes. PMID- 26999309 TI - Preventing Smoking Relapse After Delivery--Maintaining a Pregnant Pause. PMID- 26999310 TI - Theoretical analysis of the combined effects of sulfur vacancies and analyte adsorption on the electronic properties of single-layer MoS2. AB - We report a first-principles theoretical investigation on the electronic structure and electron transport of defective single-layer (SL) MoS2, as well as of corresponding structures adsorbed with benzyl viologen (BV), which was shown to provide improved performance of a field effect transistor. O2 adsorption was included to gain an understanding of the response upon air-exposure. Following analysis of the structure and stability of sulfur single vacancy and line defects in SL MoS2, we investigated the local transport at the adsorbed sites via a transport model that mimics a scanning tunneling spectroscopy experiment. Distinct current-voltage characteristics were indicated for adsorbed oxygen species at a sulfur vacancy. The electronic structures of defective MoS2 indicated the emergence of impurity states in the bandgap due to sulfur defects and oxygen adsorption. Electron transport calculations for the MoS2 surface with an extended defect in a device setting demonstrated that physisorption of BV enhances the output current, while facile chemisorption by O2 upon air-exposure causes degradation of electron transport. PMID- 26999305 TI - Movement and Physiological Demands of Australasian National Rugby League Referees. AB - PURPOSE: To evaluate the movement and physiological demands of Australasian National Rugby League (NRL) referees, officiating with a 2-referee (ie, lead and pocket) system, and to compare the demands of the lead and pocket referees. METHODS: Global positioning system devices (10 Hz) were used to obtain 86 data sets (lead, n = 41; pocket, n = 45) on 19 NRL referees. Total distance, relative distance covered, and heart rate per half and across match play were examined within and between referees using t tests. Distance, time, and number of movement "efforts" were examined in 6 velocity classifications (ie, standing <0.5, walking 0.51-2.0, jogging 2.01-4.0, running 4.01-5.5, high-speed running 5.51-7.0, and sprinting >7.0 m/s) using analysis of variance. Cohen d effect sizes are reported. RESULTS: There were no significant differences between the lead and pocket referees for any movement or physiological variable. There was an overall significant (large, very large) effect for distance (% distance) and time (% time) (P < .001) between velocity classifications for both the lead and pocket referees. Both roles covered the largest distance and number of efforts at velocities of 0.51-2.0 m/s and 2.01-4.0 m/s, which were interspersed with efforts >5.51 m/s. CONCLUSIONS: Findings highlight the intermittent nature of rugby league refereeing but show that there were no differences in the movement and physiological demands of the 2 refereeing roles. Findings are valuable for those responsible for the preparation, training, and conditioning of NRL referees and to ensure that training prepares for and simulates match demands. PMID- 26999306 TI - Cyanobacterial CO2-concentrating mechanism components: function and prospects for plant metabolic engineering. AB - Global population growth is projected to outpace plant-breeding improvements in major crop yields within decades. To ensure future food security, multiple creative efforts seek to overcome limitations to crop yield. Perhaps the greatest limitation to increased crop yield is photosynthetic inefficiency, particularly in C3 crop plants. Recently, great strides have been made toward crop improvement by researchers seeking to introduce the cyanobacterial CO2-concentrating mechanism (CCM) into plant chloroplasts. This strategy recognises the C3 chloroplast as lacking a CCM, and being a primordial cyanobacterium at its essence. Hence the collection of solute transporters, enzymes, and physical structures that make cyanobacterial CO2-fixation so efficient are viewed as a natural source of genetic material for C3 chloroplast improvement. Also we highlight recent outstanding research aimed toward the goal of introducing a cyanobacterial CCM into C3 chloroplasts and consider future research directions. PMID- 26999307 TI - Light harvesting and chloroplast electron transport in NADP-malic enzyme type C4 plants. AB - The structure of thylakoids in chloroplasts and the organization of the electron transport chain changed dynamically during the evolution of C4 photosynthesis, especially in the nicotinamide adenine dinucleotide phosphate (NADP)-malic enzyme type C4 species. Stacked grana membranes are strongly reduced in the bundle sheath chloroplasts of these plants, where photosystem II activity is diminished and cyclic electron transport around photosystem I mainly occurs. This change optimizes the ATP/NADPH production ratio in bundle sheath chloroplasts to drive the metabolic cycle of C4 photosynthesis. This review summarizes the current model of light harvesting and electron transport in the NADP-malic enzyme type C4 plants and discusses how it changed during the evolution of C4 photosynthesis. PMID- 26999311 TI - Computer-delivered interventions for reducing alcohol consumption: meta-analysis and meta-regression using behaviour change techniques and theory. AB - The current aim was to examine the effectiveness of behaviour change techniques (BCTs), theory and other characteristics in increasing the effectiveness of computer-delivered interventions (CDIs) to reduce alcohol consumption. Included were randomised studies with a primary aim of reducing alcohol consumption, which compared self-directed CDIs to assessment-only control groups. CDIs were coded for the use of 42 BCTs from an alcohol-specific taxonomy, the use of theory according to a theory coding scheme and general characteristics such as length of the CDI. Effectiveness of CDIs was assessed using random-effects meta-analysis and the association between the moderators and effect size was assessed using univariate and multivariate meta-regression. Ninety-three CDIs were included in at least one analysis and produced small, significant effects on five outcomes (d+ = 0.07-0.15). Larger effects occurred with some personal contact, provision of normative information or feedback on performance, prompting commitment or goal review, the social norms approach and in samples with more women. Smaller effects occurred when information on the consequences of alcohol consumption was provided. These findings can be used to inform both intervention- and theory development. Intervention developers should focus on, including specific, effective techniques, rather than many techniques or more-elaborate approaches. PMID- 26999308 TI - Silencing of Transient Receptor Potential Channel 4 Alleviates oxLDL-induced Angiogenesis in Human Coronary Artery Endothelial Cells by Inhibition of VEGF and NF-kappaB. AB - BACKGROUND: Transient receptor potential channel 4 (TRPC4) plays central roles in endothelial cell function. The aim of this study was to investigate the silencing effects of TRPC4 on oxidized low-density lipoprotein (oxLDL)-induced angiogenesis in human coronary artery endothelial cells (HCAECs), as well as the underlying molecular mechanism involved in this process. MATERIAL/METHODS: HCAECs were transfected with small interfering RNA (siRNA) targeting TRPC4 (TRPC4-siRNA) or with a negative control (NC)-siRNA. The expression of TRPC4 was confirmed by real time polymerase chain reaction (RT-PCR) and Western blotting. After the siRNA transfection, oxLDL was added to the medium. Cell proliferation, migration, and in vitro angiogenesis were determined by bromodeoxyuridine (BrdU) enzyme-linked immunosorbent assay (ELISA), Transwell assay and scratch-wound assay, respectively, and tube formation on Matrigel. Expression of vascular endothelial growth factor (VEGF) and nuclear factor (NF)-kappaB p65 were assessed by Western blotting. RESULTS: Both the mRNA and protein levels of TRPC4 were significantly reduced by transfection with TRPC4-siRNA compared to the control group or NC siRNA group (P<0.05). Silencing of TRPC4 significantly decreased the cell proliferation, migration, and tube formation (all P<0.05). Furthermore, the expression levels of VEGF and NF-kappaB p65 were markedly lowered by silencing of TRPC4 in HCAECs. CONCLUSIONS: These results suggest that silencing of TRPC4 alleviates angiogenesis induced by oxLDL in HCAECs through inactivation of VEGF and NF-kappaB. Suppression of TRPC4 might be an alternative therapeutic strategy for atherosclerotic neovascularization. PMID- 26999312 TI - Multiple-Step Humidity-Induced Single-Crystal to Single-Crystal Transformations of a Cobalt Phosphonate: Structural and Proton Conductivity Studies. AB - Humidity-induced multiple-step single-crystal to single-crystal (SC-SC) transformations are observed in the cobalt phosphonate (NH4)3[Co2(bamdpH)2(HCOO)(H2O)2] (1), where bamdpH4 is (benzylazanediyl)bis(methylene)diphosphonic acid, [C6H5CH2N(CH2PO3H2)2]. Under high-humidity conditions (95% RH), compound 1 experiences hydrolysis at 60 degrees C which is accompanied by the transformation from a double-chain structure of compound 1 into a single-chain structure of [Co(bamdpH2)(H2O)2].2H2O (2). When the humidity is below 10% RH, part of the lattice water in compound 2 can be released, forming a third phase, [Co(bamdpH2)(H2O)2].H2O (3). The structural transformation processes have been monitored by infrared and proton conductivity measurements. PMID- 26999314 TI - Forces between different latex particles in aqueous electrolyte solutions measured with the colloidal probe technique. AB - In this article, a compilation of results on direct force measurements between colloidal particles in monovalent salts carried out with the colloidal probe technique based on Atomic Force Microscopy was presented. The interaction forces between similar and dissimilar particles was studied and it was concluded that, in general, these force profiles may be satisfactorily quantified by the DLVO theory down to distances of few nanometers. However, in the specific case where the charge of one of the involved particle is close to neutral, it was found that the surface potential of this particle may change its sign depending on the sign of charge of the opposite particle. In this respect, the assumption that the surface potential of a particle is a property only related to the particle surface features and the bulk properties is called into question. Microsc. Res. Tech. 80:144-152, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26999313 TI - Hepatic gene transfer of human aquaporin-1 improves bile salt secretory failure in rats with estrogen-induced cholestasis. AB - The adenoviral gene transfer of human aquaporin-1 (hAQP1) water channels to the liver of 17alpha-ethinylestradiol-induced cholestatic rats improves bile flow, in part by enhancing canalicular hAQP1-mediated osmotic water secretion. To gain insight into the mechanisms of 17alpha-ethinylestradiol cholestasis improvement, we studied the biliary output of bile salts (BS) and the functional expression of the canalicular BS export pump (BSEP; ABCB11). Adenovector encoding hAQP1 (AdhAQP1) or control vector was administered by retrograde intrabiliary infusion. AdhAQP1-transduced cholestatic rats increased the biliary output of major endogenous BS (50%-80%, P < 0.05) as well as that of taurocholate administered in choleretic or trace radiolabel amounts (around 60%, P < 0.05). Moreover, liver transduction with AdhAQP1 normalized serum BS levels, otherwise markedly elevated in cholestatic animals. AdhAQP1 treatment was unable to improve BSEP protein expression in cholestasis; however, its transport activity, assessed by adenosine triphosphate-dependent taurocholate transport in canalicular membrane vesicles, was induced by 90% (P < 0.05). AdhAQP1 administration in noncholestatic rats induced no significant changes in either biliary BS output or BSEP activity. Canalicular BSEP, mostly present in raft (high cholesterol) microdomains in control rats, was largely found in nonraft (low cholesterol) microdomains in cholestasis. Considering that BSEP activity directly depends on canalicular membrane cholesterol content, decreased BSEP presence in rafts may contribute to BSEP activity decline in 17alpha-ethinylestradiol cholestasis. In AdhAQP1 transduced cholestatic rats, BSEP showed a canalicular microdomain distribution similar to that of control rats, which provides an explanation for the improved BSEP activity. CONCLUSION: Hepatocyte canalicular expression of hAQP1 through adenoviral gene transfer promotes biliary BS output by modulating BSEP activity in estrogen-induced cholestasis, a novel finding that might help us to better understand and treat cholestatic disorders. (Hepatology 2016;64:535-548). PMID- 26999316 TI - Correction: Effectiveness of Home Visits in Pregnancy as a Public Health Measure to Improve Birth Outcomes. PMID- 26999315 TI - Extensive ab initio study of the electronic states of BSe radical including spin orbit coupling. AB - The internally contracted multi-reference configuration interaction method (MRCI) with Davidson modification and the Douglas-Kroll scalar relativistic correction has been used to calculate the BSe molecule at the level of aug-cc-pV5Z basis set. The calculated electronic states, including 9 doublet and 6 quartet Lambda-S states, are correlated to the dissociation limit of B((2)P(u))+Se((3)P(g)) and B((2)P(u))+Se((1)D(g)). The Spin-orbit coupling (SOC) interaction is taken into account via the state interaction approach with the full Breit-Pauli Hamiltonian operator, which causes the entire 15 Lambda-S states to split into 32Omega states. This is the first time that the spin-orbit coupling calculation has been carried out on BSe. The potential energy curves of the Lambda-S and Omega electronic states are depicted with the aid of the avoided crossing rule between electronic states of the same symmetry. The spectroscopic constants of the bound Lambda-S and Omega states were determined, which are in good agreement with the experimental data. The transition dipole moments (TDMs) and the Franck-Condon factors (FCs) of the transitions from the low-lying bound Omega states A(2)Pi(I)3/2, B(2)Pi(I)1/2 and C(2)Delta(I)3/2 to the ground state X(2)Sigma(+)1/2 have also been presented. Based on the previous calculations, the radiative lifetimes of the A(2)Pi(I)3/2, B(2)Pi(I)1/2 and C(2)Delta(I)3/2 were evaluated. PMID- 26999317 TI - Melatonin-Induced Nocturnal Vasodilatation Contributes to Skin Regeneration Reply. PMID- 26999318 TI - Analysis of l-DOPA-derived melanin and a novel degradation product formed under alkaline conditions. AB - When the therapeutic drug l-DOPA, which is used to treat Parkinson's disease, is combined with magnesium oxide (MgO), a formulation change produces a dark substance. Infrared spectroscopy reveals that this substance is melanin. After allowing the l-DOPA and MgO mixture to stand, the l-DOPA content decreases significantly, and a new degradation product (the final degradation product of l DOPA, FDP-D) is generated. Formation of this product requires a solution with a pH of >10, and the presence of MgO is not necessary. FDP-D is not produced by tyrosinase decomposition of l-DOPA and is therefore not a melanin-related compound. Pure FDP-D is isolated by adjusting the l-DOPA solution to pH 10 with ammonium hydroxide, allowing it to stand for 3 days at room temperature, adding trifluoroacetic acid (TFA), filtering the precipitate, and separating the supernatant with high-performance liquid chromatography (HPLC). Mass spectrometry indicates that the isolated FDP-D has a molecular formula of C9H9NO7. On the basis of NMR analysis ((1)H NMR, (13)C NMR, DEPT, H-H COSY, HMQC, and HMBC), FDP D appears to be a substance with the novel structure 7a-hydroxy-5-oxo 1,2,3,5,7,7a-hexahydropyrano [3,4-b]pyrrole-2,7-dicarboxylic acid. PMID- 26999319 TI - Determination of azide impurity in sartans using reversed-phase HPLC with UV detection. AB - A simple and robust, gradient HPLC method was developed for determination of azide ppm (MUgg(-1)) levels in different sartans (irbesartan, candesartan, valsartan). The sartan was dissolved in 0.1M NaOH. Then pH was adjusted to 4.5 with 20% H3PO4 followed by dilution with water. Precipitated API was removed by filtration using 0.45MUm membrane PVDF (Polyvinylidene Fluoride) membrane filter, and supernatant was analyzed by gradient elution HPLC at room temperature with Hydro RP HPLC 250*4.6mm, 4MUm column and UV detection at 205nm. The best sensitivity was achieved by UV detection cell with 60mm optical path length: LOD 0.17MUgg(-1) and LOQ 0.84MUgg(-1) for azide. The USP requirement for maximum azide content in irbesartan is 10MUgg(-1). The analytical method was validated as per International Conference on Harmonization (ICH) guidelines with respect to system precision, intraday precision (repeatability), intermediate precision (ruggedness), linearity, quantitation limit, detection limit, accuracy, standard and sample solution stability, robustness and selectivity/specificity. The method was linear in the range from LOQ (0.84MUgg(-1)) to 101MUgg(-1) of azide. The correlation coefficient was 0.9999 and bias on y-axis for 84MUgg(-1) test concentration was 0.33%. The accuracy of the method was established based on the recovery obtained between 94.0% and 103.0% for azide. Standard and sample solutions were stable for at least 48h at room temperature and in refrigerator. The method was found to be robust for variation in column temperature (+/-5 degrees C) and mobile phase flow rate (+/-0.2mLmin(-1)) and selective for anions such as bromide, nitrate, nitrite, formate and acetate. PMID- 26999320 TI - Thermal stability of synthetic thyroid hormone l-thyroxine and l-thyroxine sodium salt hydrate both pure and in pharmaceutical formulations. AB - In this paper, the thermal stability of pure l-thyroxine (THY) and l-thyroxine sodium salt hydrate (THYSS) vs. two pharmaceutical solid formulations commercialized on both Romanian and European market (with a content of 100MUg, respectively 200MUg THYSS per tablet) were investigated. In order to determine whether the presence of excipients affects the thermal stability of the active pharmaceutical ingredient (API), the preliminary study of thermal stability in air atmosphere was completed with an in-depth solid-state kinetic study. By kinetic analysis, the non-isothermal degradation of the selected active pharmaceutical ingredients vs. the solid formulation with strength of 200MUg THYSS per tablet was investigated. Isoconversional methods (Kissinger-Akahira Sunose, Flynn-Wall-Ozawa and Friedman) were employed for the estimation of activation energies values, at five different heating rates, beta=5, 7, 10, 12 and 15 degrees Cmin(-1). Also, a fourth method was applied in the processing of data, namely NPK, allowing an objective separation in the physical and chemical processes that contribute to the thermal degradation of the selected compounds. A discussion of thermal stability from the kinetic point of view is also presented. PMID- 26999322 TI - Qualitative grading of disc degeneration by magnetic resonance in the lumbar and cervical spine: lack of correlation with histology in surgical cases. AB - BACKGROUND: Clinically, magnetic resonance (MR) imaging is the most effective non invasive tool for assessing IVD degeneration. Histological examination of the IVD provides a more detailed assessment of the pathological changes at a tissue level. However, very few reports have studied the relationship between these techniques. Identifying a relationship may allow more detailed staging of IVD degeneration, of importance in targeting future regenerative therapies. OBJECTIVES: To investigate the relationship between MR and histological grading of IVD degeneration in the cervical and lumbar spine in patients undergoing discectomy. METHODS: Lumbar (N = 99) and cervical (N = 106) IVD samples were obtained from adult patients undergoing discectomy surgery for symptomatic IVD herniation and graded to ascertain a histological grade of degeneration. The pre operative MR images from these patients were graded for the degree of IVD (MR grade) and vertebral end-plate degeneration (Modic Changes, MC). The relationship between histological and MR grades of degeneration were studied. RESULTS: In lumbar and cervical IVD the majority of samples (93%) exhibited moderate levels of degeneration (ie MR grades 3-4) on pre-operative MR scans. Histologically, most specimens displayed moderate to severe grades of degeneration in lumbar (99%) and cervical spine (93%). MR grade was weakly correlated with patient age in lumbar and cervical study groups. MR and histological grades of IVD degeneration did not correlate in lumbar or cervical study groups. MC were more common in the lumbar than cervical spine (e.g. 39 versus 20% grade 2 changes; p < 0.05), but failed to correlate with MR or histological grades for degeneration. CONCLUSIONS: In this surgical series, the resected IVD tissue displayed moderate to severe degeneration, but there is no correlation between MR and histological grades using a qualitative classification system. There remains a need for a quantitative, non-invasive, pre-clinical measure of IVD degeneration that correlates with histological changes seen in the IVD. PMID- 26999321 TI - Pharmacokinetics and brain uptake of HIV-1 replication inhibitor DB213 in Sprague Dawley rats. AB - The current study aims to investigate the pharmacokinetics and brain uptake of HIV-1 replication inhibitor DB213 via a developed LC/MS/MS analytical method. A sensitive, selective, accurate and reliable LC/MS/MS method for determination and quantification of DB213 in rat plasma and brain was developed and validated. A triple quadrupole mass spectrometer equipped with electrospray ionization (ESI) source was applied for the detection of DB213 and benzamidine (Internal Standard). The analytes were quantified by using multiple reaction monitoring (MRM) mode with m/z 333.4->86.1 and m/z 121.2->104 for DB213 and benzamidine respectively. Chromatographic separation of DB213 and benzamidine was achieved on a SunFire C8 (4.6*250mm, i.d. 5MUm) analytical column with gradient elution of a mobile phase consisted of acetonitrile and 20mM ammonium formate buffer (containing 0.5% formic acid). The method achieved good linearity from 1.95~1000ng/ml (r(2)=0.999) in plasma and 0.98~125ng/ml (r(2)=0.999) in brain. The validated method was successfully applied to plasma pharmacokinetics (PK) and brain uptake of intravenous administration of DB213 water solution (1mg/kg) to Sprague-Dawley rats. It was found that the area under the plasma concentration time curve from 0 to 360min (AUC0->360min) was 184422.1+/-42450.8ngmin/ml and the elimination half-life of DB213 after intravenous administration was 70.9+/ 16.1min. In addition, DB213 has demonstrated a potential to cross the blood-brain barrier via intravenous administration with a brain tissue concentration of 11.3+/-3.6ng/g peaked at 30min post-dosing. PMID- 26999323 TI - The Effect of Stimulus Intensity and Carrier Frequency on Auditory Middle- and Long-Latency Evoked Potentials Using a Steady-State-Response Approach. AB - PURPOSE: The purpose of this study was to measure magnitude changes of auditory steady-state responses (ASSRs) and respective transient middle- and long-latency responses as a function of stimulus intensity and carrier frequency. The literature lacks clear consensus, including relationship to loudness. METHOD: A cohort of 48 adults with normal hearing was examined from a companion study (Tlumak, Durrant, & Delgado, 2015) on effects of aging. ASSRs were elicited by repeated tone-burst stimuli presented at rates of 40 and 0.75 Hz at 3 frequencies and 5 levels of stimulus intensity. The design also permitted scrutiny of any gender bias to the results. RESULTS: Similar to derived transient response findings, ASSR magnitude (harmonic sum) systematically increased with intensity. Input-output function only at 0.75 Hz approximated a log-log linear function. However, slopes fell well below that of doubling of loudness per 10 dB SPL. Results failed to demonstrate significance as a function of carrier frequency and gender for both repetition rates. CONCLUSION: Effects of stimulus intensity, carrier frequency, and gender on ASSRs were similar to those of their transient counterparts. Findings remain disappointing for objective loudness estimation. Results suggest only a clear linkage to the long-latency response and the 0.75-Hz magnitude but require careful consideration of limitations/underlying mechanisms when measuring loudness-related effects. PMID- 26999324 TI - Positive effects of a computerised working memory and executive function training on sentence comprehension in aphasia. AB - Aphasia, the language disorder following brain damage, is frequently accompanied by deficits of working memory (WM) and executive functions (EFs). Recent studies suggest that WM, together with certain EFs, can play a role in sentence comprehension in individuals with aphasia (IWA), and that WM can be enhanced with intensive practice. Our aim was to investigate whether a combined WM and EF training improves the understanding of spoken sentences in IWA. We used a pre post-test case control design. Three individuals with chronic aphasia practised an adaptive training task (a modified n-back task) three to four times a week for a month. Their performance was assessed before and after the training on outcome measures related to WM and spoken sentence comprehension. One participant showed significant improvement on the training task, another showed a tendency for improvement, and both of them improved significantly in spoken sentence comprehension. The third participant did not improve on the training task, however, she showed improvement on one measure of spoken sentence comprehension. Compared to controls, two individuals improved at least in one condition of the WM outcome measures. Thus, our results suggest that a combined WM and EF training can be beneficial for IWA. PMID- 26999326 TI - Medicolegal--Malpractice and Ethical Issues in Radiology. Potential Risks When Dealing With Self-Referred Patients. PMID- 26999327 TI - Women's experiences of daily life after anterior cervical decompression and fusion surgery: A qualitative interview study. AB - OBJECTIVE: To explore and describe women's experiences of daily life after anterior cervical decompression and fusion surgery. DESIGN: Qualitative explorative design. SUBJECTS: Fourteen women aged 39-62 years (median 52 years) were included 1.5-3 years after anterior cervical decompression and fusion for cervical disc disease. METHODS: Individual semi-structured interviews were analysed by qualitative content analysis with an inductive approach. RESULTS: The women described their experiences of daily life in 5 different ways: being recovered to various extents; impact of remaining symptoms on thoughts and feelings; making daily life work; receiving support from social and occupational networks; and physical and behavioural changes due to interventions and encounters with healthcare professionals. CONCLUSION: This interview study provides insight into women's daily life after anterior cervical decompression and fusion. Whilst the subjects improved after surgery, they also experienced remaining symptoms and limitations in daily life. A variety of mostly active coping strategies were used to manage daily life. Social support from family, friends, occupational networks and healthcare professionals positively influenced daily life. These findings provide knowledge about aspects of daily life that should be considered in individualized postoperative care and rehabilitation in an attempt to provide better outcomes in women after anterior cervical decompression and fusion. PMID- 26999325 TI - Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies. AB - The design, synthesis and pharmacological activities of a group of 5,5 diphenylimidazolidine-2,4-dione bearing anilide, phenacyl and benzylidene fragments 2-27 were reported. The prepared 5,5-diphenylimidazolidine-2,4-dione derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 5, 9, 10, 13, and 14 showed significant and potent anti-inflammatory and analgesic activities almost equivalent to reference drug celecoxib. In COX 1/2 inhibition assay, compounds 5, 9, 10 and 14 showed high COX-2 inhibitory activity (IC50 = 0.70 MUM, 0.44 MUM, 0.61 MUM and 0.41 MUM; respectively) and selectivity index (SI) range of 142-243 comparable to celecoxib [COX-2 (SI) > 333]. These potent COX-2 inhibitors 9, 10, 13, and 14 were docked into the active site pocket of COX-2 to explore the binding mode and possible interactions of these ligands. PMID- 26999328 TI - Immunopathogenesis and therapeutic approaches in pediatric celiac disease. AB - Celiac Disease is an autoimmune enteropathy with increasing incidence worldwide in both adults and children. It occurs as an inflammatory condition with destruction of the normal architecture of villi on consumption of gluten and related protein products found in wheat, barley and rye. However, the exact pathogenesis is not yet fully understood. A gluten-free diet remains the main modality of therapy to date. While some patients continue to have symptoms even on a gluten-free diet, adherence to this diet is also difficult, especially for the children. Hence, there is continued interest in novel methods of therapy and the current research focus is on the promising novel non-dietary modalities of treatment. Here, we critically reviewed the existing literature regarding the pathogenesis of celiac disease in children including the role of in-utero exposure leading to neonatal and infant sensitization and its application for the development of new therapeutic approaches for these patients. PMID- 26999329 TI - Stereotactic body radiotherapy for pancreatic cancer: recent progress and future directions. AB - Despite advances in surgical, medical, and radiation therapy for pancreatic cancer, the prognosis remains poor. At this time, the only chance for long-term survival is surgical resection. More challenging is the optimal management of unresectable locally advanced pancreatic cancer, which has historically been treated with concurrent chemoradiation or chemotherapy alone. However, the survival and local control benefit of conventional radiotherapy in addition to chemotherapy was unclear. More recently, stereotactic body radiotherapy (SBRT) is emerging as a viable approach to maximizing local tumor control with a tolerable side effect profile. SBRT achieves sharp dose fall-off facilitating safe delivery of highly focused radiation to the tumor over 1-5 days. Although the optimal regimen of pancreas SBRT has not yet been established, its short treatment course limits the delay of additional. Future directions involve prospective study of pancreas SBRT and exploration of biomarkers and imaging technology in order to adopt a personalized management paradigm. PMID- 26999332 TI - Dynamics of Molecular Orientation Observed Using Angle Resolved Photoemission Spectroscopy during Deposition of Pentacene on Graphite. AB - A real-time method to observe both the structural and the electronic configuration of an organic molecule during deposition is reported for the model system of pentacene on graphite. Structural phase transition of the thin films as a function of coverage is monitored by using in situ angle resolved photoemission spectroscopy (ARPES) results to observe the change of the electronic configuration at the same time. A photoemission theory that uses independent atomic center approximations is introduced to identify the molecular orientation from the ARPES technique. This study provides a practical insight into interpreting ARPES data regarding dynamic changes of molecular orientation during initial growth of molecules on a well-defined surface. PMID- 26999330 TI - Monokine induced by interferon gamma (MIG/CXCL9) is an independent prognostic factor in newly diagnosed myeloma. AB - Immune suppression is a hallmark of multiple myeloma (MM), but data on soluble factors involved in the fate of immune effector cells are limited. The CXCR3 binding chemokine monokine induced by interferon-gamma (MIG/CXCL9) has been associated with tumor progression, immune escape, and angiogenesis in several malignancies. We here aimed to evaluate the prognostic relevance of MIG in MM. MIG serum levels were significantly elevated in newly diagnosed MM patients (n = 105) compared to patients with monoclonal gammopathy of undetermined significance (MGUS; n = 17) and healthy controls (n = 37). MIG expression in stromal compartments but not purified MM cells correlated with serum levels. High MIG serum levels were significantly associated with established prognostic markers (international staging system: R = 0.25, p = 0.001; age: R = 0.47, p < 0.0001; lactate-dehydrogenase: R = 0.34, p = 0.0005) and poor overall survival (OS) (median OS 17.0 months vs. not reached, p < 0.001). A similar association was found for CXCL10 and CXCL11. Multivariate regression analysis indicated MIG as an independent prognostic factor of OS. PMID- 26999331 TI - Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation. AB - Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation. PMID- 26999333 TI - Asiatic acid attenuated apoptotic and inflammatory stress in the striatum of MPTP treated mice. AB - The effects of post-treatments with asiatic acid (AA) at 20, 40 or 80 mg per kg BW per day against apoptotic, oxidative and inflammatory injury in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were examined. The results showed that AA supplements at 40 and 80 mg per kg BW per day increased AA deposit in the striatum, increased glutathione content and decreased reactive oxygen species production in the striatum. AA supplements at 20-80 mg per kg BW per day dose-dependently lowered striatal levels of nitric oxide, 3-nitrotyrosine, interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E2. AA supplements at 40 and 80 mg per kg BW per day down regulated striatal p47(phox) and gp91(phox) expression; but, at three test doses suppressed striatal expression of inducible nitric oxide synthase and cyclooxygenase-2. AA post-treatments at 40 and 80 mg per kg BW per day enhanced Bcl-2 expression, and lowered Bax, apoptosis-inducing factor and caspase-3 expression in the striatum. AA at 20-80 mg per kg BW per day up-regulated striatal tyrosine hydroxylase expression, and suppressed Toll-like receptors (TLR)2 and nuclear factor kappa B p65 expression. AA treatments at 40 and 80 mg per kg BW per day decreased striatal expression of alpha-synuclein and TLR4, increased striatal levels of dopamine, brain-derived nerve growth factor and glial cell line-derived neurotrophic factor. These novel findings suggest that asiatic acid is a potent nutraceutical agent against the progression of Parkinson's disease. PMID- 26999334 TI - Synthesis and structural insight into ESX-1 Substrate Protein C, an immunodominant Mycobacterium tuberculosis-secreted antigen. AB - Tuberculosis, the second leading cause of death from a single infectious agent, is recognized as a major threat to human health due to a lack of practicable vaccines against the disease and the widespread occurrence of drug resistance. With a pressing need for a novel protein target as a platform for new vaccine development, ESX-1 Substrate Protein C (EspC) was recently identified as a novel Mycobacterium tuberculosis-secreted antigen that is as immunodominant as the two specific immunodiagnostic T-cell antigens, CFP-10 and ESAT-6. Here, we present the first chemical total synthesis, folding conditions, and circular dichroism data of EspC. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 267 274, 2016. PMID- 26999335 TI - Comparison of covered and uncovered self-expandable stents in the treatment of malignant biliary obstruction. AB - BACKGROUND AND OBJECTIVE: Drainage with metallic stents is the treatment of choice in malignant obstructive jaundice. Technical and clinical success with metallic stents is obtained in over 90% and 80% of cases, respectively. There are self-expandable metallic stents designed to increase permeability. The aim of this study was to describe the results obtained with totally covered self expandable and uncovered self-expandable metallic stents in the palliative treatment of malignant biliary obstruction. PATIENTS AND METHODS: Sixty eight patients with malignant obstructive jaundice secondary to pancreatobiliary or metastatic disease not amenable to surgery were retrospectively included. Two groups were created: group A (covered self-expandable metallic stents) (n = 22) and group B (uncovered self-expandable metallic stents) (n = 46). RESULTS: Serum total bilirubin, direct bilirubin, alkaline phosphatase and gamma glutamyl transferase levels decreased in both groups and no statistically significant difference was detected (p = 0.800, p = 0.190, p = 0.743, p = 0.521). Migration was greater with covered stents but it was not statistically significant either (p = 0.101). Obstruction was greater in the group with uncovered stents but it was not statistically significant either (p = 0.476). CONCLUSION: There are no differences when using covered self-expandable stents or uncovered self expandable stents in terms of technical and clinical success or complications in the palliative treatment of malignant obstructive jaundice. PMID- 26999337 TI - Fluorescence In Situ Hybridization for Melanoma Diagnosis: A Review and a Reappraisal. AB - Although conventional histopathological examination is the undisputable mainstay for the diagnosis of melanocytic skin neoplasms, fluorescence in situ hybridization (FISH) has the potential to provide important information to morphologically challenging cases. The standard melanoma FISH test targeting RREB1 (6p25), MYB (6q23), CCND1 (11q13), and centromere 6 is an effective compromise between cost, technical complexity, and sensitivity. The authors use the standard FISH-positivity as a tie-breaker for challenging melanocytic neoplasms mainly in a non-Spitzoid morphologic context because the currently available test leaves several unresolved issues: namely, a relatively low diagnostic accuracy in morphologically ambiguous melanocytic neoplasms; a relatively low sensitivity and specificity in Spitzoid neoplasms; and the occurrence of false positives due to tetraploidy in Spitz nevi and in nevi with an atypical epithelioid component. Under investigation is currently a new melanoma probe cocktail targeting RREB1 (6p25), C-MYC (8q24), CDKN2A (9p21), and CCND1 (11q13). However, CDKN2A is a significant parameter only if lost in homozygosis, and this complicates the interpretation of the results. Furthermore, the new melanoma probe cocktail has been tested on cases of atypical Spitzoid proliferations with fatal outcomes which at present are too few to allow definite conclusions. The authors propose the implementation of a FISH algorithm (standard 4-probe test followed by either C-MYC or CDKN2A/centromere 9) to assist the histopathological diagnosis and minimize the technical problems. Nevertheless, because the diagnostic accuracy of the FISH technique is far from being absolute, the overall clinicopathological context must always guide the decision-making process about the management of morphobiologically ambiguous melanocytic proliferations. PMID- 26999339 TI - Clinical Follow-up of Atypical Spitzoid Tumors Analyzed by Fluorescence In Situ Hybridization. AB - Many neoplasms with spitzoid features remain enigmatic, especially those with intermediate grade features or "atypical spitzoid tumors" (ASTs). Fluorescence in situ hybridization (FISH) has emerged as a complementary technique to conventional microscopy, with certain chromosomal patterns conveying diagnostic information. In this study, we examined 36 ASTs analyzed by FISH for specific abnormalities in chromosomes 6, 9, and 11. Aberrations were detected in 11 cases, 7 of which met FISH criteria for spitzoid melanoma. These had homozygous deletion of 9p21, partial deletion of 11q13, gain of 6p25, and gain of 11q13. All 3 patients with positive sentinel lymph nodes, including one with progression beyond the sentinel lymph node, had homozygous deletion of chromosome 9p21, but there were no deaths in an average of 28 months of follow-up of these cases. Other aberrations in the chromosomal pattern of ASTs were heterozygous deletion of 9p21, partial deletion of 6p23, and tetraploidy. We found that ASTs, including those eventually diagnosed as spitzoid melanoma, had a more indolent course in our cohort than conventional malignant melanoma. Moreover, the addition of FISH results led to a more definitive diagnosis in 7 cases, 4 of which had abnormalities on FISH consistent with spitzoid melanoma. PMID- 26999338 TI - Study of Epithelial to Mesenchymal Transition in Atypical Fibroxanthoma and Undifferentiated Pleomorphic Sarcoma to Discern an Epithelial Origin. AB - Atypical fibroxanthoma (AFX) is considered a fibroblastic or myofibroblastic neoplasm probably corresponding to a superficial variant of undifferentiated pleomorphic sarcoma (UPS). However, an epithelial origin has also been postulated. An immunohistochemical study of the epithelial to mesenchymal transition (EMT) phenomenon was performed in a series of 19 AFX and 4 UPS to discern an epithelial origin. A panel of epithelial (cytokeratins AE1-AE3 panel, podoplanin D2-40, and E-cadherin) and EMT (vimentin, Twist, Zeb1, and Snail1) markers were evaluated in both tumoral cells and the adjacent epidermis. Podoplanin and Snail1 were negative in all the samples. Nuclear E-cadherin, Twist, and Zeb1 were detected in most lesions, as previously reported in other sarcomas. In the epidermis, E-cadherin showed a normal membranous pattern and only isolated cells were positive for vimentin. Twist and Zeb1 were mainly negative in the epidermis. None of the immunohistochemical markers mentioned above elicited a conspicuous bridging between the epidermis and the dermis. Our findings suggest that EMT does not play a role in the development of AFX or UPS. PMID- 26999336 TI - Torsional power study using CENTURION phacoemulsification technology. AB - BACKGROUND: To evaluate the effect of varying levels of power on phacoemulsification efficiency using the CENTURION Vision System. METHODS: Formalin-soaked porcine lenses were divided into 2-mm cubes; 0.9-mm, balanced tips were used. Torsional power levels were tested from 10% to 100% at 10% intervals. Vacuum was set to 550 mmHg, aspiration to 50 ml/min, and intraocular pressure at 50 mmHg. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were determined. RESULTS: Increasing torsional power up to 60% increased efficiency. This effect was linear from 30 to 60% power (R2 = .90; P < 0.05). There were no significant differences in efficiency past 60%. Chatter was highest at 10% power and decreased linearly (R2 = .87; P = 0.007) as power was increased up to 60% power, and chatter did not improve above this power level. CONCLUSIONS: Power improved efficiency only up to a 60% power level, and then was negligible. Chatter correlated well with power up to the 60% level, so that as power was increased, chatter decreased. Because there are no additional benefits in efficiency past 60% power, and because chatter is minimal at 60% power, we recommend torsional ultrasound at 60% as the optimal power setting for using the CENTURION System for phacoemulsification.l. PMID- 26999340 TI - A 36-Year-Old Man With an Enlarging Nodule on the Buttock. PMID- 26999341 TI - Breast Cancer Metastasis Misdiagnosed as an Angiokeratomatous Eruption. An Infrequent Presentation. Case Report. AB - INTRODUCTION: Cutaneous metastases represent 2% of all metastases. Breast cancer is the most common cause of skin metastases. Schwartz described 8 types of cutaneous breast metastases; one uncommon form is carcinoma telangiectodes (CT), which may resemble angiosarcoma or lymphangioma circumscriptum. However, there are no reports of CT misdiagnosed as eruptive angiokeratomas. CASE REPORT: The authors describe the clinical, histopathologic, and immunohistochemical features of a unique case of CT. Clinical examination revealed an itchy, dark blue-reddish scaly papular eruption that resembled angiokeratomas. The papules were grouped in a zosteriform pattern on the right chest. A biopsy of the papules revealed intravascular thrombi of neoplastic cells and erythrocytes. The neoplastic cells were pleomorphic and with mitotic figures. Immunohistochemical analysis revealed expression of HER-2-neu in neoplastic cells but negative for estrogen and progesterone receptors. The involved vessels were positive for CD31 and negative for podoplanin. This immunoprofile demonstrated intravascular spread of aggressive breast carcinoma. CONCLUSION: CT is an uncommon form of cutaneous metastasis from breast carcinoma with less than 10 cases described in the literature. There are no previous reported cases of CT mimicking angiokeratomas, although lymphangioma circumscriptum-like lesion may occasionally resemble angiokeratomas. A unique clinical presentation of CT is described. PMID- 26999343 TI - Rituximab-Induced Serum Sickness-Like Reaction: A Histopathologic Viewpoint. PMID- 26999344 TI - Mycobacterium leprae Is Usually Positive to Periodic Acid-Schiff and Grocott Stains. PMID- 26999345 TI - Acantholytic-Like Pattern in a Recurrent Melanoma Mimicking Acantholytic Squamous Cell Carcinoma: A Further Example Highlighting the Potential for Misdiagnosis. PMID- 26999346 TI - Deep Penetrating Fibrous Histiocytoma: A Case Report and Implications for Surgical Management. AB - Deep penetrating fibrous histiocytoma (DPFH) is a rare variant of fibrous histiocytoma that can arise in the subcutis and deep soft tissues with different clinical implications from dermatofibromas. Dermatofibromas are mainly cosmetic annoyances and do not require surgical management. However, the DPFH does require that negative surgical margins be achieved because of the possibility of local recurrence and distant metastasis. We describe a case of a 24-year-old man diagnosed with DPFH through histologic examination and immunohistochemistry. The lesion displayed diffuse, strong D2-40 positivity and a minority of cells were highlighted with factor XIIIa. The lesion was negative for CD34. The patient's lesion was incompletely excised and a repeat excision was required. PMID- 26999347 TI - Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders. AB - The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. PMID- 26999351 TI - Interactive effects within the prototype willingness model: Predicting the drinking behavior of indigenous early adolescents. AB - Drawing on the Prototype/Willingness Model of Adolescent Risk Behavior, we used longitudinal data collected from North American Indigenous early adolescents (ages 10-12 years) to examine the interactive effects of favorable drinker prototypes, perceived drinking norms, and past-year drinking behavior on subsequent drinking behavior (i.e., drinking behavior 1 year later and growth in drinking behavior from 1-5 years later). We found that the positive association between favorable drinker prototypes and drinking 1 year later was strongest for adolescents who were high in past-year drinking and perceived low drinking norms. The interaction pattern for growth in drinking was more complex and suggested an important pattern; specifically, favorable drinker prototypes were positively associated with drinking 5 years later, but only for adolescents who reported no past-year drinking and perceived low drinking norms. The theoretical and practical implications of these results are discussed. PMID- 26999348 TI - Sodium-glucose cotransporter 2 inhibitors and cardiovascular outcomes. AB - Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cardiovascular (CV) morbidity and mortality. Furthermore, many patients with T2DM have comorbidities that are risk factors for CV disease. While intensive glucose control reduces the risk of diabetic microvascular complications, its relationship to CV outcomes remains unclear. Consequently, the management of CV risk factors in patients with T2DM is complex, and factors other than blood glucose must be considered. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of oral glucose-lowering agents, are associated with reductions in blood pressure and body weight, in addition to decreasing hyperglycemia, and therefore have the potential to reduce CV risk in patients with T2DM. The clinical trial results of SGLT2 inhibitors regarding CV safety and outcomes are discussed, including data from the recently published EMPA-REG OUTCOME study. This trial was the first dedicated CV outcomes study to demonstrate that a glucose-lowering agent lowered CV mortality and all-cause mortality, and reduced hospitalization for heart failure in patients with T2DM at high risk of CV events. PMID- 26999350 TI - Within treatment therapeutic alliance ratings profiles predict posttreatment frequency of alcohol use. AB - Although past research has demonstrated a positive relationship between the therapeutic alliance (TA) and improved drinking outcomes, specific aspects of the alliance have received less attention. In this study, we examined the association between alliance characteristics during treatment and 4-month follow-up drinking reports. Sixty-five treatment-seeking alcohol dependent clients who participated in 12 weeks of individual outpatient treatment provided weekly TA ratings during treatment and reported on pretreatment, during treatment, and posttreatment alcohol use. Latent profile analysis was conducted to discern distinct profiles of client and therapist ratings of therapeutic alliance with similar alliance characteristics. TA profiles were based on clients' and therapists' mean alliance rating, minimum alliance rating, maximum alliance rating, the range of alliance ratings, and the difference in session number between maximum and minimum alliance ratings. One- through 4-class models were fit to the data. Model fit was judged by comparative fit indices, substantive interpretability, and parsimony. Wald tests of mean equality determined whether classes differed on follow-up percentage of days abstinent (PDA) at 4-months posttreatment. Three-profile solutions provided the best fit for both client and therapist ratings of the therapeutic alliance. Client alliance rating profiles predicted drinking in the follow-up period, but therapist rating profiles did not. These results suggest that distinct profiles of the therapeutic alliance can be identified and that client alliance rating profiles are associated with frequency of alcohol use following outpatient treatment. PMID- 26999353 TI - Immediate effects of plain packaging health warnings on quitting intention and potential mediators: Results from two ecological momentary assessment studies. AB - The purpose of this study is to examine the immediate, everyday impact of health warnings on cigarette packages on potential smoking cessation mediators and to test for differences in immediate reactions to branded and plain tobacco packaging during the transition phase when plain packs where first introduced in Australia. Two Ecological Momentary Assessment studies tested whether smokers report higher risk appraisals, self-efficacy, and quitting intentions immediately after seeing a warning compared to random times of the day (Study 1), and whether smoking from plain packs results in higher quitting intention, risk appraisal, and self-efficacy than smoking from branded packs (Study 2). There was no immediate increase in self-efficacy, risk appraisal, or intention after encountering health warnings, and no differences in cognitions when using plain compared with branded packs. Moreover, cognitions were not different when warnings were encountered in proximity to smoking compared to nonsmoking events. However, self-efficacy and risk appraisal were significantly associated with quitting intention. Current health warnings do not seem to have an immediate impact on important predictors of quitting intention and might benefit from including messages that place a stronger focus on increasing smokers' confidence that they can quit. Replication of the results with larger sample and cluster sizes is warranted. PMID- 26999349 TI - Drinking group characteristics related to willingness to engage in protective behaviors with the group at nightclubs. AB - Electronic music dance events (EMDEs) in nightclubs are settings where young adults tend to engage in high-risk behaviors, such as heavy alcohol and drug use. Consequences of these behaviors may be prevented if young adults engage in protective strategies with their drinking group. It is important to identify drinking group characteristics that predict willingness to intervene with peers. Objectives of this study were to (a) examine whether young adults at EMDEs would be willing to intervene with members of their drinking group and (b) identify both individual and group characteristics of drinking groups that predict willingness to intervene. Nightclub patrons (N = 215 individuals; 80 groups) were surveyed anonymously as they entered clubs. Individual- and group-level characteristics were measured in relation to willingness to intervene with peers. Mixed-model regressions were conducted, accounting for nesting by drinking group. Analyses show that participants were willing to intervene with their peers. Groups that knew each other well and had lower expectations for members' drinking were more willing to intervene. Women, younger, and older participants were also more willing to intervene. Findings show that club patrons are willing to intervene with their drinking groups to protect them from harmful consequences of heavy drinking and drug use. Findings indicate characteristics of both individuals and drinking groups that could be targeted in interventions among young adults largely not being reached by college interventions. PMID- 26999352 TI - Reciprocal relations between internalizing symptoms and frequency of alcohol use: Findings from a longitudinal study of Mexican-origin youth. AB - AIMS: Alcohol consumption and internalizing symptoms, which often co-occur, pose considerable risk to the developing adolescent and have lasting public health consequences. Previous research has documented concurrent associations between alcohol use and symptoms of anxiety and depression, but the dearth of longitudinal research, particularly for ethnic minority youth, raises questions about the replicability and causal direction of these effects. The goal of the present research was to clarify these issues, and investigate whether different facets of anxiety and depression are uniquely associated with alcohol use in adolescence. METHOD: The present research examined cross-lagged relations between frequency of alcohol use and internalizing symptoms, using data from a longitudinal study of 674 Mexican-origin youth (50% female) assessed at ages 14 and 16. RESULTS: Alcohol use at age 14 prospectively predicted increases in overall internalizing symptoms, and overall internalizing symptoms at age 14 prospectively predicted increases in alcohol use. Reciprocal effects were consistently found for the general distress and anxious arousal facets, but not for anhedonic depression and a scale measuring the cognitive aspects of anxiety. CONCLUSIONS: The findings provide evidence of reciprocal relations between alcohol use and internalizing symptoms, but also highlight the danger of treating all symptoms of anxiety and depression as interchangeable components of a single broad domain. Instead, symptoms common to both anxiety and depressive disorders (e.g., general distress) have the most robust reciprocal relations with alcohol use. Thus, intervention programs aimed at reducing early alcohol use by Mexican origin youth should target this component of the internalizing domain. PMID- 26999354 TI - The relationship between addictive use of social media and video games and symptoms of psychiatric disorders: A large-scale cross-sectional study. AB - Over the last decade, research into "addictive technological behaviors" has substantially increased. Research has also demonstrated strong associations between addictive use of technology and comorbid psychiatric disorders. In the present study, 23,533 adults (mean age 35.8 years, ranging from 16 to 88 years) participated in an online cross-sectional survey examining whether demographic variables, symptoms of attention-deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), anxiety, and depression could explain variance in addictive use (i.e., compulsive and excessive use associated with negative outcomes) of two types of modern online technologies: social media and video games. Correlations between symptoms of addictive technology use and mental disorder symptoms were all positive and significant, including the weak interrelationship between the two addictive technological behaviors. Age appeared to be inversely related to the addictive use of these technologies. Being male was significantly associated with addictive use of video games, whereas being female was significantly associated with addictive use of social media. Being single was positively related to both addictive social networking and video gaming. Hierarchical regression analyses showed that demographic factors explained between 11 and 12% of the variance in addictive technology use. The mental health variables explained between 7 and 15% of the variance. The study significantly adds to our understanding of mental health symptoms and their role in addictive use of modern technology, and suggests that the concept of Internet use disorder (i.e., "Internet addiction") as a unified construct is not warranted. PMID- 26999358 TI - Radioactive Barium Ion Trap Based on Metal-Organic Framework for Efficient and Irreversible Removal of Barium from Nuclear Wastewater. AB - Highly efficient and irreversible capture of radioactive barium from aqueous media remains a serious task for nuclear waste disposal and environmental protection. To address this task, here we propose a concept of barium ion trap based on metal-organic framework (MOF) with a strong barium-chelating group (sulfate and sulfonic acid group) in the pore structures of MOFs. The functionalized MOF-based ion traps can remove >90% of the barium within the first 5 min, and the removal efficiency reaches 99% after equilibrium. Remarkably, the sulfate-group-functionalized ion trap demonstrates a high barium uptake capacity of 131.1 mg g(-1), which surpasses most of the reported sorbents and can selectively capture barium from nuclear wastewater, whereas the sulfonic-acid group-functionalized ion trap exhibits ultrafast kinetics with a kinetic rate constant k2 of 27.77 g mg(-1) min(-1), which is 1-3 orders of magnitude higher than existing sorbents. Both of the two MOF-based ion traps can capture barium irreversibly. Our work proposes a new strategy to design barium adsorbent materials and provides a new perspective for removing radioactive barium and other radionuclides from nuclear wastewater for environment remediation. Besides, the concrete mechanisms of barium-sorbent interactions are also demonstrated in this contribution. PMID- 26999356 TI - Clinical Significance of Community- and Healthcare-Acquired Carbapenem-Resistant Enterobacteriaceae Isolates. AB - This study was conducted to investigate the clinical significance, manifestations, microbiological characteristics and outcomes of carbapenem resistant Enterobacteriaceae (CRE) isolates, and compare the clinical features of community- and healthcare-acquired CRE isolates. A total of 78 patients were identified to have CRE. Klebsiella pneumoniae was the most common pathogens (n = 42, 53.8%), followed by Enterobacter cloacae (n = 24, 30.8%), and Escherichia coli (n = 11, 14.1%). Most of the patients acquired CRE from healthcare settings (n = 55, 70.5%), and other cases got CRE from community settings (n = 23, 29.5%). Nine cases (11.5%) were classified as CRE colonization. Among the remaining 69 cases of CRE infections, pneumonia (n = 28, 40.6%) was the most common type of infections, followed by urinary tract infection (n = 24, 34.8%), and intra abdominal infection (n = 16, 23.2%). The patients acquired CRE from community settings were more likely to be elderly, female, and had more urinary tract infections than from healthcare settings. In contrast, the patients acquired CRE from healthcare settings had more intra-abdominal infections, intra-abdominal surgery, and presence of indwelling device than from community settings. In conclusion, community-acquired CRE are not rare, and their associated clinical presentations are different from healthcare-acquired CRE. PMID- 26999355 TI - InP Nanoflag Growth from a Nanowire Template by in Situ Catalyst Manipulation. AB - Quasi-two-dimensional semiconductor materials are desirable for electronic, photonic, and energy conversion applications as well as fundamental science. We report on the synthesis of indium phosphide flag-like nanostructures by epitaxial growth on a nanowire template at 95% yield. The technique is based on in situ catalyst unpinning from the top of the nanowire and its induced migration along the nanowire sidewall. Investigation of the mechanism responsible for catalyst movement shows that its final position is determined by the structural defect density along the nanowire. The crystal structure of the "flagpole" nanowire is epitaxially transferred to the nanoflag. Pure wurtzite InP nanomembranes with just a single stacking fault originating from the defect in the flagpole that pinned the catalyst were obtained. Optical characterization shows efficient highly polarized photoluminescence at room temperature from a single nanoflag with up to 90% degree of linear polarization. Electric field intensity enhancement of the incident light was calculated to be 57, concentrated at the nanoflag tip. The presented growth method is general and thus can be employed for achieving similar nanostructures in other III-V semiconductor material systems with potential applications in active nanophotonics. PMID- 26999357 TI - Murine Splenic Natural Killer Cells Do Not Develop Immunological Memory after Re Encounter with Mycobacterium bovis BCG. AB - Several lines of evidence have recently suggested that natural killer (NK) cells develop immunological memory against viral infections. However, there is no apparent evidence that NK cells acquire specific memory against Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only currently licensed vaccine for preventing tuberculosis. In the present study, we investigated whether murine splenic NK cells can be activated by BCG in a dendritic cell (DC)-independent or dependent manner, and furthermore examined whether these NK cells acquire specific memory following BCG vaccination. NK cells isolated from spleens of BCG immunized mice produced interferon (IFN)gamma through direct BCG stimulation in the absence of antigen-presenting cells; however, NK cells from control animals similarly directly responded to BCG, and the response level was not statistically significant between the immunized and the naive NK cells. When purified NK cells that had been exposed to BCG were cocultured with RAW murine macrophages infected with BCG, the antibacterial activity of the macrophages was strongly enhanced; however, its level was similar to that by naive NK cells, which had not been exposed to BCG. When splenocytes harvested from BCG-immunized mice were stimulated with purified protein derivative (PPD) derived from Mycobacterium tuberculosis, a specific IFNgamma response was clearly observed, mainly attributed to NK cells and memory CD4+ T cells. To investigate whether these NK cells as well as the T cells are activated by cell-cell interaction with DCs presenting mycobacterial antigens, NK cells isolated from BCG-immunized mice were cocultured with splenocytes harvested from naive mice in the presence of PPD stimulation. However, no IFNgamma response was found in the NK cells. These results suggest that murine splenic NK cells do not develop BCG-specific immunological memory in either a DC-independent or -dependent manner. PMID- 26999360 TI - Detection of four different amino acid neurotransmitters in cultured rat neurons and the culture medium by precolumn derivatization high-performance liquid chromatography. AB - We validated and used a high-performance liquid chromatography procedure for the determination of four different amino acid neurotransmitters in cultured rat neurons and used culture medium. Samples were derivatized using 2,4 dinitrofluorobenzene and the amino acids were separated on a C18 column. The method yielded good reproducibility and sensitivity for the quantification of the four free amino acid neurotransmitters, with average recovery factors of 80.25 118.43%, an intraday precision of 0.09-0.17%, and an interday precision of 0.62 0.74%. The assay method can be readily utilized as a precise, sensitive, and highly accurate method for the determination of concentrations of the four amino acid neurotransmitters in cultured rat neurons and used culture medium. Using the described methods, we found that the aspartate, glutamic acid, glycine, and gamma aminobutyric acid concentrations (umol/g protein) in cultured rat neurons were 25.23+/-0.81, 35.16+/-0.32, 77.56+/-4.51, and 62.87+/-3.12, respectively, whereas their concentrations (uM) in the used culture medium were 18.18+/-0.82, 24.27+/ 1.01, 107.18+/-9.56, and 35.78+/-2.98, respectively. PMID- 26999361 TI - Neuroprotective and anti-inflammatory effects of lidocaine in kainic acid injected rats. AB - Lidocaine, the most commonly used local anesthetic, inhibits glutamate release from nerve terminals. Given the involvement of glutamate neurotoxicity in the pathogenesis of various neurological disorders, this study investigated the role of lidocaine in hippocampal neuronal death and inflammatory events induced by an i.p. injection of kainic acid (KA) (15 mg/kg), a glutamate analog. The results showed that KA significantly led to neuronal death in the CA3 pyramidal layers of the hippocampus and this effect was attenuated by the systemic administration of lidocaine (0.8 or 4 mg/kg, i.p.) 30 min before KA injection. Moreover, KA-induced microglia activation and gene expression of proinflammatory cytokines, namely, interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, in the hippocampus were reduced by the lidocaine pretreatment. Altogether, the results suggest that lidocaine can effectively treat glutamate excitotoxicity-related brain disorders. PMID- 26999359 TI - Hybridization Capture Using RAD Probes (hyRAD), a New Tool for Performing Genomic Analyses on Collection Specimens. AB - In the recent years, many protocols aimed at reproducibly sequencing reduced genome subsets in non-model organisms have been published. Among them, RAD sequencing is one of the most widely used. It relies on digesting DNA with specific restriction enzymes and performing size selection on the resulting fragments. Despite its acknowledged utility, this method is of limited use with degraded DNA samples, such as those isolated from museum specimens, as these samples are less likely to harbor fragments long enough to comprise two restriction sites making possible ligation of the adapter sequences (in the case of double-digest RAD) or performing size selection of the resulting fragments (in the case of single-digest RAD). Here, we address these limitations by presenting a novel method called hybridization RAD (hyRAD). In this approach, biotinylated RAD fragments, covering a random fraction of the genome, are used as baits for capturing homologous fragments from genomic shotgun sequencing libraries. This simple and cost-effective approach allows sequencing of orthologous loci even from highly degraded DNA samples, opening new avenues of research in the field of museum genomics. Not relying on the restriction site presence, it improves among sample loci coverage. In a trial study, hyRAD allowed us to obtain a large set of orthologous loci from fresh and museum samples from a non-model butterfly species, with a high proportion of single nucleotide polymorphisms present in all eight analyzed specimens, including 58-year-old museum samples. The utility of the method was further validated using 49 museum and fresh samples of a Palearctic grasshopper species for which the spatial genetic structure was previously assessed using mtDNA amplicons. The application of the method is eventually discussed in a wider context. As it does not rely on the restriction site presence, it is therefore not sensitive to among-sample loci polymorphisms in the restriction sites that usually causes loci dropout. This should enable the application of hyRAD to analyses at broader evolutionary scales. PMID- 26999362 TI - Multilevel Upper Body Movement Control during Gait in Children with Cerebral Palsy. AB - Upper body movements during walking provide information about balance control and gait stability. Typically developing (TD) children normally present a progressive decrease of accelerations from the pelvis to the head, whereas children with cerebral palsy (CP) exhibit a general increase of upper body accelerations. However, the literature describing how they are transmitted from the pelvis to the head is lacking. This study proposes a multilevel motion sensor approach to characterize upper body accelerations and how they propagate from pelvis to head in children with CP, comparing with their TD peers. Two age- and gender-matched groups of 20 children performed a 10m walking test at self-selected speed while wearing three magneto-inertial sensors located at pelvis, sternum, and head levels. The root mean square value of the accelerations at each level was computed in a local anatomical frame and its variation from lower to upper levels was described using attenuation coefficients. Between-group differences were assessed performing an ANCOVA, while the mutual dependence between acceleration components and the relationship between biomechanical parameters and typical clinical scores were investigated using Regression Analysis and Spearman's Correlation, respectively (alpha = 0.05). New insights were obtained on how the CP group managed the transmission of accelerations through the upper body. Despite a significant reduction of the acceleration from pelvis to sternum, children with CP do not compensate for large accelerations, which are greater than in TD children. Furthermore, those with CP showed negative sternum-to-head attenuations, in agreement with the documented rigidity of the head-trunk system observed in this population. In addition, the estimated parameters proved to correlate with the scores used in daily clinical practice. The proposed multilevel approach was fruitful in highlighting CP-TD gait differences, supported the in-field quantitative gait assessment in children with CP and might prove beneficial to designing innovative intervention protocols based on pelvis stabilization. PMID- 26999367 TI - Registry-based outcome assessment in haemophilia: a scoping study to explore the available evidence. AB - Haemophilia is a congenital disorder with bleeding episodes as its primary symptom. These episodes can result in negative outcomes including joint damage, loss of active days due to hospitalization and reduced quality of life. Effective treatment, however, can improve the outcome. Registries have been used as a valuable source of information regarding the monitoring of treatment and outcome. The two main aims of this exploratory study were to establish which haemophilia registries publish peer-reviewed outcome assessment research and then to extract, classify and report the treatment outcomes and their extent of use in the retrieved registries. Using relevant keywords, we searched PubMed and Web of Science databases for publications during the period 1990-2015. Retrieved references were screened in a stepwise process. Eligible papers were original full articles on haemophilia outcomes that used data from a computerized patient database. Descriptive results were summarized. Of 2352 references reviewed, 25 full texts were eligible for inclusion in the study. These papers were published by 11 registries ranging from local to international in coverage. It is still relatively rare for registries to produce peer-reviewed publications about outcomes, and most that currently do produce such papers are located in Europe and North America. More information is available on traditional outcomes such as comorbidities and arthropathy than on health-related quality of life or the social and developmental impact of haemophilia on patients. Inhibitors, HIV and viral hepatitis are amongst the most commonly reported comorbidities. Research has focused more on factor consumption and less on hospitalization or time lost at school or work due to haemophilia. Haemophilia registries, especially those at the national level, are valuable resources for the delivery of effective health care to patients. Validated outcome measurement instruments are essential for the production of reliable and accurate evidence. Finally, such evidence should be communicated to physicians, patients, the public and health policymakers. PMID- 26999368 TI - Radionuclides in ornithogenic sediments as evidence for recent warming in the Ross Sea region, Antarctica. AB - Radionuclides including (210)Pb, (226)Ra and (137)Cs were analyzed in eight ornithogenic sediment profiles from McMurdo Sound, Ross Sea region, East Antarctica. Equilibration between (210)Pb and (226)Ra were reached in all eight profiles, enabling the determination of chronology within the past two centuries through the Constant Rate of Supply (CRS) model. Calculated fluxes of both (210)Pb and (137)Cs varied drastically among four of the profiles (MB4, MB6, CC and CL2), probably due to differences in their sedimentary environments. In addition, we found the flux data exhibiting a clear decreasing gradient in accordance with their average deposition rate, which was in turn related to the specific location of the profiles. We believe this phenomenon may correspond to global warming of the last century, since warming-induced surface runoff would bring more inflow water and detritus to the coring sites, thus enhancing the difference among the profiles. To verify this hypothesis, the deposition rate against age of the sediments was calculated based on their determined chronology, which showed ascending trends in all four profiles. The significant increase in deposition rates over the last century is probably attributable to recent warming, implying a potential utilization of radionuclides as environmental indicators in this region. PMID- 26999366 TI - Conjugation of Microcystins with Thiols Is Reversible: Base-Catalyzed Deconjugation for Chemical Analysis. AB - Microcystins are potent cyclic heptapeptide toxins found in many freshwater cyanobacteria. Most microcystins contain an alpha,beta-unsaturated amide that can react with thiol-containing amino acids, peptides, and proteins in vivo and in vitro. While soluble conjugates formed from small peptides can be extracted and analyzed directly by LC-MS, microcystins conjugated to proteins are analyzed after oxidative cleavage of their Adda side chains, but information on which microcystin analogues were present is lost. Observations during the development of thiol-derivatization-based LC-MS methods for microcystin analysis indicated that the reaction of thiols with microcystins was reversible. The kinetics of deconjugation was investigated with mercaptoethanol as a model thiol to identify suitable reaction conditions. A range of microcystins conjugated to mercaptoethanol, methanethiol, cysteine, and glutathione were then successfully deconjugated, demonstrating the feasibility of releasing conjugated forms of microcystins for chemical analysis. Reagents for removing the released thiols or for trapping the released microcystins increased the reaction rate. Optimization of methodologies based on this reaction should increase the method's utility for measuring free and conjugated microcystins. The results also indicate that thiol conjugated microcystins slowly release free microcystins, even at neutral pH, with consequences for assessment of toxin exposure, metabolism, and trophic transfer. A range of other common natural and environmental toxins, such as deoxynivalenol and acrylamide, also contain alpha,beta-unsaturated carbonyl groups and can be expected to behave in a similar manner. PMID- 26999369 TI - Degradation of the pharmaceuticals diclofenac and sulfamethoxazole and their transformation products under controlled environmental conditions. AB - Contamination of the aquatic environment by pharmaceuticals via urban effluents is well known. Several classes of drugs have been identified in waterways surrounding these effluents in the last 15years. To better understand the fate of pharmaceuticals in ecosystems, degradation processes need to be investigated and transformation products must be identified. Thus, this study presents the first comparative study between three different natural environmental conditions: photolysis and biodegradation in aerobic and anaerobic conditions both in the dark of diclofenac and sulfamethoxazole, two common drugs present in significant amounts in impacted surface waters. Results indicated that degradation kinetics differed depending on the process and the type of drug and the observed transformation products also differed among these exposure conditions. Diclofenac was nearly degraded by photolysis after 4days, while its concentration only decreased by 42% after 57days of exposure to bacteria in aerobic media and barely 1% in anaerobic media. For sulfamethoxazole, 84% of the initial concentration was still present after 11days of exposure to light, while biodegradation decreased its concentration by 33% after 58days of exposure under aerobic conditions and 5% after 70days of anaerobic exposure. In addition, several transformation products were observed and persisted over time while others degraded in turn. For diclofenac, chlorine atoms were lost primarily in the photolysis, while a redox reaction was promoted by biodegradation under aerobic conditions. For sulfamethoxazole, isomerization was favored by photolysis while a redox reaction was also favored by the biodegradation under aerobic conditions. To summarize this study points out the occurrence of different transformation products under variable degradation conditions and demonstrates that specific functional groups are involved in the tested natural attenuation processes. Given the complexity of environmental samples more analytical effort is needed to fully identify new products of potential toxicity. PMID- 26999363 TI - Placental Size Is Associated Differentially With Postnatal Bone Size and Density. AB - We investigated relationships between placental size and offspring adolescent bone indices using a population-based, mother-offspring cohort. The Avon Longitudinal Study of Parents and Children (ALSPAC) recruited pregnant women from the southwest of England between 1991 and 1993. There were 12,942 singleton babies born at term who survived at least the first 12 months. From these, 8933 placentas were preserved in formaldehyde, with maternal permission for their use in research studies. At the approximate age of 15.5 years, the children underwent a dual-energy X-ray absorptiometry (DXA) scan (measurements taken of the whole body minus head bone area [BA], bone mineral content [BMC], and areal bone mineral density [aBMD]). A peripheral quantitative computed tomography (pQCT) scan (Stratec XCT2000L; Stratec, Pforzheim, Germany) at the 50% tibial site was performed at this visit and at approximately age 17.7 years. In 2010 a sample of 1680 placentas were measured and photographed. To enable comparison of effect size across different variables, predictor and outcome variables were standardized to Z-scores and therefore results may be interpreted as partial correlation coefficients. Complete placental, DXA, and pQCT data were available for 518 children at age 15.5 years. After adjustment for gender, gestational age at birth, and age at time of pQCT, the placental area was positively associated with endosteal circumference (beta [95% CI]: 0.21 [0.13, 0.30], p < 0.001), periosteal circumference (beta [95% CI]: 0.19 [0.10, 0.27], p < 0.001), and cortical area (beta [95% CI]: 0.10 [0.01, 0.18], p = 0.03), and was negatively associated with cortical density (beta [95% CI]: -0.11 [-0.20, -0.03], p = 0.01) at age 15.5 years. Similar relationships were observed for placental volume, and after adjustment for additional maternal and offspring covariates. These results suggest that previously observed associations between placental size and offspring bone development persist into older childhood, even during puberty, and that placental size is differentially related to bone size and volumetric density. (c) 2016 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). PMID- 26999365 TI - Plasma High-Mannose and Complex/Hybrid N-Glycans Are Associated with Hypercholesterolemia in Humans and Rabbits. AB - N-glycans play important roles in various pathophysiological processes and can be used as clinical diagnosis markers. However, plasma N-glycans change and their pathophysiological significance in the setting of hypercholesterolemia, a major risk factor for atherosclerosis, is unknown. Here, we collected plasma from both hypercholesterolemic patients and cholesterol-fed hypercholesterolemic rabbits, and determined the changes in the whole-plasma N-glycan profile by electrospray ionization mass spectrometry. We found that both the hypercholesterolemic patients and rabbits showed a dramatic change in their plasma glycan profile. Compared with healthy subjects, the hypercholesterolemic patients exhibited higher plasma levels of a cluster of high-mannose and complex/hybrid N-glycans (mainly including undecorated or sialylated glycans), whereas only a few fucosylated or fucosylated and sialylated N-glycans were increased. Additionally, cholesterol-fed hypercholesterolemic rabbits also displayed increased plasma levels of high-mannose in addition to high complex/hybrid N-glycan levels. The whole-plasma glycan profiles revealed that the plasma N-glycan levels were correlated with the plasma cholesterol levels, implying that N-glycans may be a target for treatment of hypercholesterolemia. PMID- 26999364 TI - Whole-Genome Saliva and Blood DNA Methylation Profiling in Individuals with a Respiratory Allergy. AB - The etiology of respiratory allergies (RA) can be partly explained by DNA methylation changes caused by adverse environmental and lifestyle factors experienced early in life. Longitudinal, prospective studies can aid in the unravelment of the epigenetic mechanisms involved in the disease development. High compliance rates can be expected in these studies when data is collected using non-invasive and convenient procedures. Saliva is an attractive biofluid to analyze changes in DNA methylation patterns. We investigated in a pilot study the differential methylation in saliva of RA (n = 5) compared to healthy controls (n = 5) using the Illumina Methylation 450K BeadChip platform. We evaluated the results against the results obtained in mononuclear blood cells from the same individuals. Differences in methylation patterns from saliva and mononuclear blood cells were clearly distinguishable (PAdj<0.001 and |Deltabeta|>0.2), though the methylation status of about 96% of the cg-sites was comparable between peripheral blood mononuclear cells and saliva. When comparing RA cases with healthy controls, the number of differentially methylated sites (DMS) in saliva and blood were 485 and 437 (P<0.05 and |Deltabeta|>0.1), respectively, of which 216 were in common. The methylation levels of these sites were significantly correlated between blood and saliva. The absolute levels of methylation in blood and saliva were confirmed for 3 selected DMS in the PM20D1, STK32C, and FGFR2 genes using pyrosequencing analysis. The differential methylation could only be confirmed for DMS in PM20D1 and STK32C genes in saliva. We show that saliva can be used for genome-wide methylation analysis and that it is possible to identify DMS when comparing RA cases and healthy controls. The results were replicated in blood cells of the same individuals and confirmed by pyrosequencing analysis. This study provides proof-of-concept for the applicability of saliva-based whole genome methylation analysis in the field of respiratory allergy. PMID- 26999371 TI - FBXL12 regulates T-cell differentiation in a cell-autonomous manner. AB - Aldehyde dehydrogenase (ALDH) activity is a hallmark of stem cells including embryonic, adult tissue and cancer stem cells. The SCF(FBXL) (12) complex is an authentic ubiquitin ligase that targets ALDH3 for degradation. FBXL12 is essential for the differentiation of trophoblast stem cells into specific cell types in the placenta during mouse embryogenesis, but its physiological functions in adult tissues have remained unknown. We have now investigated the role of the FBXL12-ALDH3 axis in the thymus, in which FBXL12 was most abundant among adult mouse tissues examined. During T-cell differentiation, FBXL12 is most abundant in CD4(+) CD8(+) (DP) cells, with its expression declining as these cells differentiate into CD4(+) CD8(-) or CD4(-) CD8(+) (SP) cells. T cells of FBXL12 null mice manifested a differentiation block at the DP-SP transition that was associated with ALDH3 accumulation in DP cells. This differentiation block was also apparent in wild-type mouse recipients of FBXL12-null bone marrow transplants as well as in FBXL12-null fetal thymic organ culture, suggesting that it is a cell-autonomous phenomenon in the thymus rather than an indirect effect of altered systemic conditions. Our results thus indicate that, in addition to its role in placental development, the FBXL12-ALDH3 axis is required for maturation of undifferentiated thymocytes. PMID- 26999372 TI - Impact of Firearm Availability and Gun Regulation on State Suicide Rates. AB - Past studies on suicide have investigated the association of firearm ownership and suicide risk in the United States. The aim of the present study was to build on previous work by examining the impact of firearm storage practices and the strictness of firearm regulation on suicide rates at the state level. Data were compiled from primarily three sources. Suicide and firearm ownership information was obtained from the Centers for Disease Control and Prevention. Strictness of handgun regulation was derived from figures available at the Law Center to Prevent Violence, and controls were taken from the US Bureau of the Census. Mixed models were fitted to the data. Household firearm ownership was strongly associated with both suicide by all mechanisms, and firearm suicide. Storage practices had especially elevated consequences on suicide rates. Percent with loaded guns and gun readiness increased suicide rates, and strictness of gun regulation reduced suicide rates. Ready access to firearms can make a difference between life and death. Loaded and unlocked firearms within reach become risk factors for fatal outcomes from suicidal behavior. Future research might want to examine ways of obtaining more recent data on individual firearm ownership. This study proposes several policy recommendations for suicide prevention. PMID- 26999374 TI - The power of science diplomacy, a lesson from the Nobel laureate Peter Agre. PMID- 26999373 TI - Discovery of New E-Selectin Inhibitors by Virtual Screening, Fluorescence Binding Assays, and STD NMR Experiments. AB - E-selectin is an endothelial protein that participates in the adhesion of metastatic cancer cells, and is therefore a relevant target for antitumor therapeutic intervention. In this work, virtual screening was used to identify new E-selectin inhibitors from a subset of drug-like molecules retrieved from the ZINC database, including the physiological ligand sLe(x) as reference structure (PDB ID: 1G1T). Four hits were chosen and subjected to molecular dynamics simulations and fluorescence binding assays, which led to the determination of experimental dissociation constants between 333 and 1012 MUm. The candidate with the highest affinity was studied by saturation transfer difference (STD) NMR experiments and complete relaxation and conformational exchange matrix analysis of saturation transfer (CORCEMA-ST), aimed at identifying the preferable binding mode with E-selectin. Our results revealed that this new inhibitor binds more strongly than sLe(x) in the E-selectin binding site, in good agreement with simulation predictions. These properties will prove valuable for the future design of drugs that target E-selectin. PMID- 26999370 TI - Clinical instrumentation and applications of Raman spectroscopy. AB - Clinical diagnostic devices provide new sources of information that give insight about the state of health which can then be used to manage patient care. These tools can be as simple as an otoscope to better visualize the ear canal or as complex as a wireless capsule endoscope to monitor the gastrointestinal tract. It is with tools such as these that medical practitioners can determine when a patient is healthy and to make an appropriate diagnosis when he/she is not. The goal of diagnostic medicine then is to efficiently determine the presence and cause of disease in order to provide the most appropriate intervention. The earliest form of medical diagnostics relied on the eye - direct visual observation of the interaction of light with the sample. This technique was espoused by Hippocrates in his 5th century BCE work Epidemics, in which the pallor of a patient's skin and the coloring of the bodily fluids could be indicative of health. In the last hundred years, medical diagnosis has moved from relying on visual inspection to relying on numerous technological tools that are based on various types of interaction of the sample with different types of energy - light, ultrasound, radio waves, X-rays etc. Modern advances in science and technology have depended on enhancing technologies for the detection of these interactions for improved visualization of human health. Optical methods have been focused on providing this information in the micron to millimeter scale while ultrasound, X-ray, and radio waves have been key in aiding in the millimeter to centimeter scale. While a few optical technologies have achieved the status of medical instruments, many remain in the research and development phase despite persistent efforts by many researchers in the translation of these methods for clinical care. Of these, Raman spectroscopy has been described as a sensitive method that can provide biochemical information about tissue state while maintaining the capability of delivering this information in real-time, non invasively, and in an automated manner. This review presents the various instrumentation considerations relevant to the clinical implementation of Raman spectroscopy and reviews a subset of interesting applications that have successfully demonstrated the efficacy of this technique for clinical diagnostics and monitoring in large (n >= 50) in vivo human studies. PMID- 26999375 TI - Luminescent InP Quantum Dots with Tunable Emission by Post-Synthetic Modification with Lewis Acids. AB - We demonstrate the ability of M(2+) Lewis acids (M = Cd, Zn) to dramatically enhance the photoluminescence quantum yield (PL QY) of InP quantum dots. The addition of cadmium and zinc is additionally found to red- and blue-shift, respectively, the lowest energy absorption and emission of InP quantum dots while maintaining particle size. This treatment results in a facile strategy to post synthetically tune the luminescence color in these materials. Optical and structural characterization (XRD, TEM, XAS, ICP) have led us to identify the primary mechanism of PL turn-on as surface passivation of phosphorus dangling bonds, affording PL QYs up to 49% without the growth of a type I shell or the addition of HF. This route to PL enhancement and color tuning may prove useful as a standalone treatment or as a complement to shelling strategies. PMID- 26999377 TI - The Development and Application of Two-Chamber Reactors and Carbon Monoxide Precursors for Safe Carbonylation Reactions. AB - Low molecular weight gases (e.g., carbon monoxide, hydrogen, and ethylene) represent vital building blocks for the construction of a wide array of organic molecules. Whereas experimental organic chemists routinely handle solid and liquid reagents, the same is not the case for gaseous reagents. Synthetic transformations employing such reagents are commonly conducted under pressure in autoclaves or under atmospheric pressure with a balloon setup, which necessitates either specialized equipment or potentially hazardous and nonrecommended installations. Other safety concerns associated with gaseous reagents may include their toxicity and flammability and, with certain gases, their inability to be detected by human senses. Despite these significant drawbacks, industrial processes apply gaseous building blocks regularly due to their low cost and ready availability but nevertheless under a strictly controlled manner. Carbon monoxide (CO) fits with all the parameters for being a gas of immense industrial importance but with severe handling restrictions due to its inherent toxicity and flammability. In academia, as well as research and development laboratories, CO is often avoided because of these safety issues, which is a limitation for the development of new carbonylation reactions. With our desire to address the handling of CO in a laboratory setting, we designed and developed a two-chamber reactor (COware) for the controlled delivery and utilization of stoichiometric amounts of CO for Pd-catalyzed carbonylation reactions. In addition to COware, two stable and solid CO-releasing molecules (COgen and SilaCOgen) were developed, both of which release CO upon activation by either Pd catalysis or fluoride addition, respectively. The unique combination of COware with either COgen or SilaCOgen provides a simple reactor setup enabling synthetic chemists to easily perform safe carbonylation chemistry without the need for directly handling the gaseous reagent. With this technology, an array of low-pressure carbonylations were developed applying only near stoichiometric amounts of carbon monoxide. Importantly, carbon isotope variants of the CO precursors, such as (13)COgen, Sila(13)COgen, or even (14)COgen, provide a simple means for performing isotope labeling syntheses. Finally, the COware applicability has been extended to reactions with other gases, such as hydrogen, CO2, and ethylene including their deuterium and (13)C-isotopically labeled versions where relevant. The COware system has been repeatedly demonstrated to be a valuable reactor for carrying out a wide number of transition metal-catalyzed transformations, and we believe this technology will have a significant place in many organic research laboratories. PMID- 26999378 TI - Synthesis of Naphthylpyridines from Unsymmetrical Naphthylheptadiynes and the Configurational Stability of the Biaryl Axis. AB - A series of different unsymmetrically substituted naphthyl-based diynes were synthesized. These substrates formed the foundation for the assembly of novel biaryls containing pyridine moieties with differently substituted five-membered rings in the backbone of the newly formed heterobiaryl system. The key step for their efficient construction was the photo- and cobalt-catalyzed [2 + 2 + 2] cycloaddition reaction between the corresponding naphthyldiyne and aceto- or benzonitrile. The heterobiaryl products have been isolated and investigated with respect to the configurational stability of their biaryl axis using dynamic chiral HPLC; subtle effects of the substitution pattern on the stability of the axis were observed. For several compounds the activation barriers (DeltaG(?)) of racemization were determined. Suitable substitution of the five-membered ring backbone exemplarily allowed the Co-catalyzed enantioselective cyclization to yield the enantiomerically enriched heterobiaryl. PMID- 26999379 TI - Absence of socioeconomic inequalities in access to good-quality breast cancer treatment within a population-wide screening programme in Turin (Italy). AB - Several studies suggest that population-based breast cancer screening programmes might help reduce social inequalities in breast cancer survival both by increasing early diagnosis and by improving access to effective treatments. To start disentangling the two effects, we evaluated social inequalities in quality of treatment of screen-detected breast cancer in the city of Turin (Italy). Combining data from the Audit System on Quality of Breast Cancer Treatment and the Turin Longitudinal Study, we analysed 2700 cases in the screening target age class 50-69 diagnosed in the period 1995-2008. We selected 10 indicators of the pathway of care, relative to timeliness and appropriateness of diagnosis and treatment, and three indicators of socioeconomic position: education, occupational status and housing characteristics. For each indicator of care, relative risks of failure were estimated by robust Poisson regression models, controlling for calendar period of diagnosis, size of tumour and activity volume of the surgery units. The principal predictor of failure of the good care indicators was the calendar period of diagnosis, with a general improvement with time in the quality of diagnosis and treatment, followed by size of the tumour and volume of activity. Socioeconomic indicators show only a marginal independent effect on timeliness indicators. The observed associations of quality indicators with socioeconomic characteristics are lower than expected, suggesting a possible role of the screening programme in reducing disparities in the access to good quality treatments thanks to its capability to enter screen-detected women into a protected pathway of care. PMID- 26999380 TI - Epidemiology and genetic susceptibility of malignant melanoma in North Sardinia, Italy. AB - The aim of this report was to study the descriptive and genetic epidemiology of malignant melanoma in North Sardinia, Italy, in the period 1992-2011. Epidemiological data were obtained from the local tumor registry, which is part of the Italian Association for Tumor Registries. Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. The overall number of cases registered was 532. The male-to-female ratio was 1 : 1 and the mean age was 56 years for men and 55 years for women. The standardized incidence rates were 4.9/100 000 and 4.4/100 000 and the standardized mortality rates were 1.7/100 000 and 1.3/100 000 for men and women, respectively. The relative 5-year survival was 77% for men and 79% for women. In our series, 24/316 (7.6%) patients had a familial occurrence of melanoma (presence of at least one additional family member affected). Among these, one variant (Gly23Asp), reported previously as a low-frequency disease-causing mutation, was detected by mutational screening in the p16 gene only. With the exception of polymorphisms, none of either the sporadic melanoma patients or healthy controls presented a germline mutation in candidate genes. An increase in incidence and a decrease in mortality rates of malignant melanoma were registered in North Sardinia, from 1992 to 2011, whereas survival was similar to that reported in recent international reports. The high-penetrance melanoma susceptibility genes (CDKN2A and CDK4) are not involved in predisposition to melanoma in North Sardinia. PMID- 26999382 TI - Giant viruses come of age. AB - Viruses with genomes up to a few megabases in length are a common occurrence in nature, even though they have escaped our notice until recently. These giant viruses infect mainly single-celled eukaryotes and isolation efforts concentrating on amoebal hosts alone have spawned hundreds of viral isolates, featuring viruses with previously unseen virion morphologies and the largest known viral genomes and particles. One of the challenges that lie ahead is to analyze and categorize the available data and to establish an approved classification system that reflects the evolutionary relationships and biological properties of these viruses. Extensive sampling of Acanthamoeba-infecting mimiviruses and initial characterization of their virophage parasites have provided a first blueprint of the genetic diversity and composition of a giant virus clade that will facilitate the taxonomic grouping of these fascinating microorganisms. PMID- 26999381 TI - Metabolic Power Method: Underestimation of Energy Expenditure in Field-Sport Movements Using a Global Positioning System Tracking System. AB - The purpose of this study was to assess the validity of a global positioning system (GPS) tracking system to estimate energy expenditure (EE) during exercise and field-sport locomotor movements. Twenty-seven participants each completed a 90-min exercise session on an outdoor synthetic futsal pitch. During the exercise session, they wore a 5-Hz GPS unit interpolated to 15 Hz and a portable gas analyzer that acted as the criterion measure of EE. The exercise session was composed of alternating 5-minute exercise bouts of randomized walking, jogging, running, or a field-sport circuit (*3) followed by 10 min of recovery. One-way analysis of variance showed significant (P < .01) and very large underestimations between GPS metabolic power- derived EE and oxygen-consumption (VO2) -derived EE for all field-sport circuits (% difference ~ -44%). No differences in EE were observed for the jog (7.8%) and run (4.8%), whereas very large overestimations were found for the walk (43.0%). The GPS metabolic power EE over the entire 90 min session was significantly lower (P < .01) than the VO2 EE, resulting in a moderate underestimation overall (-19%). The results of this study suggest that a GPS tracking system using the metabolic power model of EE does not accurately estimate EE in field-sport movements or over an exercise session consisting of mixed locomotor activities interspersed with recovery periods; however, is it able to provide a reasonably accurate estimation of EE during continuous jogging and running. PMID- 26999385 TI - Optimal flexible sample size design with robust power. AB - It is well recognized that sample size determination is challenging because of the uncertainty on the treatment effect size. Several remedies are available in the literature. Group sequential designs start with a sample size based on a conservative (smaller) effect size and allow early stop at interim looks. Sample size re-estimation designs start with a sample size based on an optimistic (larger) effect size and allow sample size increase if the observed effect size is smaller than planned. Different opinions favoring one type over the other exist. We propose an optimal approach using an appropriate optimality criterion to select the best design among all the candidate designs. Our results show that (1) for the same type of designs, for example, group sequential designs, there is room for significant improvement through our optimization approach; (2) optimal promising zone designs appear to have no advantages over optimal group sequential designs; and (3) optimal designs with sample size re-estimation deliver the best adaptive performance. We conclude that to deal with the challenge of sample size determination due to effect size uncertainty, an optimal approach can help to select the best design that provides most robust power across the effect size range of interest. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999383 TI - Polypharmacy-Time to Get Beyond Numbers. PMID- 26999384 TI - Activity-based costing analysis of the analgesic treatments used in postoperative pain management in Italy. AB - BACKGROUND: The aim of this analysis is to evaluate the costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in nine different Italian hospitals, defined as the cumulative cost of drugs, consumable materials and time required for anesthesiologists, surgeons and nurses to administer each analgesic technique. METHODS: Nine Italian hospitals have been involved in this study through the administration of a questionnaire aimed to acquire information about the Italian clinical practice in terms of analgesia. This study uses activity-based costing (ABC) analysis to identify, measure and give value to the resources required to provide the therapeutic treatment used in Italy to manage the postoperative pain patients face after surgery. A deterministic sensitivity analysis (DSA) has been performed to identify the cost determinants mainly affecting the final cost of each treatment analyzed. Costs have been reclassified according to three surgical macro-areas (abdominal, orthopedic and thoracic) with the aim to recognize the cost associated not only to the analgesic technique adopted but also to the type of surgery the patient faced before undergoing the analgesic pathway. RESULTS: Fifteen different analgesic techniques have been identified for the treatment of moderate to severe pain in patients who underwent a major abdominal, orthopedic or thoracic surgery. The cheapest treatment actually employed is the oral administration "around the clock" (? 8.23), whilst the most expensive is continuous peripheral nerve block (? 223.46). The intravenous patient-controlled analgesia costs ? 277.63. In terms of resources absorbed, the non-continuous administration via bolus is the gold standard in terms of cost-related to the drugs used (? 1.28), and when administered pro re nata it also absorbs the lowest amount of consumables (?0.58?) compared to all other therapies requiring a delivery device. The oral analgesic administration pro re nata is associated to the lowest cost in terms of health professionals involved (? 6.25), whilst intravenous PCA is the most expensive one (? 245.66), requiring a massive monitoring on the part of physicians and nurses. CONCLUSIONS: The analysis successfully collected information about costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in all the nine different Italian hospitals. The interview showed high heterogeneity in the treatment of moderate to severe pain after major abdominal, orthopedic and thoracic surgeries among responding anesthesiologists, with 15 different analgesic modalities reported. The majority of the analgesic techniques considered in the analysis is not recommended by any guideline and their application in real life can be one of the reasons for the high incidence of uncontrolled pain, which is still reported in the postoperative period. Health care costs have become more and more important, although the choice of the best analgesic treatment should be a compromise between efficacy and economic considerations. PMID- 26999376 TI - Unrelated donor stem cell transplantation for transfusion-dependent thalassemia. AB - Thalassemia major is characterized by severe anemia dependent on red cell transfusions from infancy. Conservative management requires a safe source of compatible blood throughout life, strategies to combat iron overload, monitoring and treatment of transfusion-related complications, and management of cardiac and/or hepatic dysfunction from iron accumulation. Complications can result in premature morbidity and mortality. Stem cell transplantation is curative, but outcomes depend on the availability of a histocompatible donor, recipient age, and disease-related complications. Successful transplantation requires stable donor engraftment and donor-derived erythropoiesis and a low incidence of graft versus-host disease, organ toxicities, and mortality. This translates to a cure with good quality of life and life span. Since recipients are at a high risk for graft rejection (prior transfusions, immunocompetency), myeloablative transplants have been the norm. Recent modifications to standard preparative regimens have significantly reduced transplant toxicities, resulting in >80% disease-free survival in children. Aiming to further reduce regimen-related toxicities, such as veno-occlusive liver disease and sterility, a recent trial explored reduced intensity conditioning in unrelated donor (URD) transplants utilizing marrow or umbilical cord blood in patients without suitable familial donors. This report summarizes advances in URD transplantation for thalassemia, focusing on conditioning regimen nuances. PMID- 26999388 TI - Type V Secretion Systems in Bacteria. AB - Type V secretion denotes a variety of secretion systems that cross the outer membrane in Gram-negative bacteria but that depend on the Sec machinery for transport through the inner membrane. They are possibly the simplest bacterial secretion systems, because they consist only of a single polypeptide chain (or two chains in the case of two-partner secretion). Their seemingly autonomous transport through the outer membrane has led to the term "autotransporters" for various subclasses of type V secretion. In this chapter, we review the structure and function of these transporters and review recent findings on additional factors involved in the secretion process, which have put the term "autotransporter" to debate. PMID- 26999386 TI - Effect of Disinfection on the Bond Strength between Denture Teeth and Microwave Cured Acrylic Resin Denture Base. AB - PURPOSE: Denture tooth debonding is a common complication for denture wearers; however, the effect of complete denture disinfection on bonding between denture teeth and acrylic resin remains unclear. The aim of this study was to evaluate the effect of disinfection methods on the bond strength between denture teeth and microwave-cured acrylic resin denture base. MATERIALS AND METHODS: Three commercial brands of denture teeth (Trilux, Biolux, Vipi Dent Plus) and one microwave-cured acrylic resin denture base were tested. Each brand of denture teeth was divided into seven groups (n = 6; estimated by partial Eta squared). The specimenss of groups H and Cl were immersed in 1% sodium hypochlorite and 4% chlorhexidine digluconate for 7 days, respectively. In group Br, the specimens were subjected to toothbrush simulation under 200 g of force for 20,000 cycles. In groups Br-H and Br-Cl, the specimens were brushed and further disinfected with 1% sodium hypochlorite and 4% chlorhexidine digluconate, respectively. In control groups 1 (Co1) and 2 (Co2), the specimens were stored in distilled water for 50 +/- 2 hours and 7 days, respectively. Shear bond strength testing was performed at the resin/tooth interface in a universal testing machine at a 1 mm/min crosshead speed. The failure pattern was quantified and classified into adhesive, cohesive, or mixed. Data were analyzed using two-way ANOVA and Tukey HSD test (alpha = 0.05). RESULTS: Disinfection with 1% sodium hypochlorite (p = 0.031), brushing (p < 0.0001), and association of brushing with either 1% sodium hypochlorite (p < 0.0001) or 4% chlorhexidine digluconate (p = 0.01) reduced the bond strength between denture teeth and microwave-cured acrylic resin denture base. All commercial brands of denture teeth presented a similar bond strength (p > 0.05). The failure pattern was predominantly adhesive independent of the disinfection method and denture tooth brand. CONCLUSIONS: Disinfection with sodium hypochlorite, brushing, and the association of mechanical and chemical methods reduced the bond strength between denture tooth and microwave-cured acrylic resin denture base. PMID- 26999389 TI - Population Phylogenomics of Extraintestinal Pathogenic Escherichia coli. AB - The emergence of genomics over the last 10 years has provided new insights into the evolution and virulence of extraintestinal Escherichia coli. By combining population genetics and phylogenetic approaches to analyze whole-genome sequences, it became possible to link genomic features to specific phenotypes, such as the ability to cause urinary tract infections. An E. coli chromosome can vary extensively in length, ranging from 4.3 to 6.2 Mb, encoding 4,084 to 6,453 proteins. This huge diversity is structured as a set of less than 2,000 genes (core genome) that are conserved between all the strains and a set of variable genes. Based on the core genome, the history of the species can be reliably reconstructed, revealing the recent emergence of phylogenetic groups A and B1 and the more ancient groups B2, F, and D. Urovirulence is most often observed in B2/F/D group strains and is a multigenic process involving numerous combinations of genes and specific alleles with epistatic interactions, all leading down multiple evolutionary paths. The genes involved mainly code for adhesins, toxins, iron capture systems, and protectins, as well as metabolic pathways and mutation rate-control systems. However, the barrier between commensal and uropathogenic E. coli strains is difficult to draw as the factors that are responsible for virulence have probably also been selected to allow survival of E. coli as a commensal in the intestinal tract. Genomic studies have also demonstrated that infections are not the result of a unique and stable isolate, but rather often involve several isolates with variable levels of diversity that dynamically changes over time. PMID- 26999390 TI - The Phylogeny of Bacillus cereus sensu lato. AB - The three main species of the Bacillus cereus sensu lato, B. cereus, B. thuringiensis, and B. anthracis, were recognized and established by the early 1900 s because they each exhibited distinct phenotypic traits. B. thuringiensis isolates and their parasporal crystal proteins have long been established as a natural pesticide and insect pathogen. B. anthracis, the etiological agent for anthrax, was used by Robert Koch in the 19th century as a model to develop the germ theory of disease, and B. cereus, a common soil organism, is also an occasional opportunistic pathogen of humans. In addition to these three historical species designations, are three less-recognized and -understood species: B. mycoides, B. weihenstephanensis, and B. pseudomycoides. All of these "species" combined comprise the Bacillus cereus sensu lato group. Despite these apparently clear phenotypic definitions, early molecular approaches to separate the first three by various DNA hybridization and 16S/23S ribosomal sequence analyses led to some "confusion" because there were limited differences to differentiate between these species. These and other results have led to frequent suggestions that a taxonomic change was warranted to reclassify this group to a single species. But the pathogenic properties of B. anthracis and the biopesticide applications of B. thuringiensis appear to "have outweighed pure taxonomic considerations" and the separate species categories are still being maintained. B. cereus sensu lato represents a classic example of a now common bacterial species taxonomic quandary. PMID- 26999393 TI - Bacterial Prostatitis: Bacterial Virulence, Clinical Outcomes, and New Directions. AB - Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because Escherichia coli represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in E. coli strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of E. coli causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain E. coli might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that E. coli needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to E. coli strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic E. coli may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain. PMID- 26999398 TI - Type VII Secretion: A Highly Versatile Secretion System. AB - Type VII secretion (T7S) systems of mycobacteria secrete substrates over the unusual diderm cell envelope. Furthermore, T7S gene clusters are present throughout the phylum Actinobacteria, and functional T7S-like systems have been identified in Firmicutes. Most of the T7S substrates can be divided into two families: the Esx proteins, which are found in both Firmicutes and Actinobacteria, and the PE and PPE proteins, which are more mycobacterium specific. Members of both families have been shown to be secreted as folded heterodimers, suggesting that this is a conserved feature of T7S substrates. Most knowledge of the mechanism of T7S and the roles of T7S systems in virulence comes from studies of pathogenic mycobacteria. These bacteria can contain up to five T7S systems, called ESX-1 to ESX-5, each having its own role in bacterial physiology and virulence. In this article, we discuss the general composition of T7S systems and the role of the individual components in secretion. These conserved components include two membrane proteins with (predicted) enzymatic activities: a predicted ATPase (EccC), likely to be required for energy provision of T7S, and a subtilisin-like protease (MycP) involved in processing of specific substrates. Additionally, we describe the role of a conserved intracellular chaperone in T7S substrate recognition, based on recently published crystal structures and molecular analysis. Finally, we discuss system-specific features of the different T7S systems in mycobacteria and their role in pathogenesis and provide an overview of the role of T7S in virulence of other pathogenic bacteria. PMID- 26999400 TI - Trends in use of contralateral prophylactic mastectomy by racial/ethnic group and ER/PR status among patients with breast cancer: A SEER population-based study. AB - BACKGROUND: While differences in CPM use between White and Black patients are well known, it is not clear whether CPM use differs by estrogen/progesterone receptor (ER/PR) status of tumors and whether racial/ethnic differences in the use are affected by ER/PR status, which varies between racial groups. The purpose of this study was to investigate whether CPM usage differs by racial/ethnic group and ER/PR status among patients in the Surveillance, Epidemiology, and End Results (SEER) data. METHODS: The study subjects were women with histologically confirmed unilateral breast cancer who underwent breast surgery between 1998 and 2011. Age-adjusted CPM use as a proportion of all surgically treated patients or all patients who had mastectomy was analyzed by racial/ethnic group, tumor behavior, and ER/PR status. Temporal trends in age-adjusted CPM use were presented by ER/PR status and racial/ethnic group. RESULTS: The analyses stratified by ER/PR status showed significant racial/ethnic differences in age adjusted CPM use with non-Hispanic White and non-Hispanic Asian/Pacific Islander (API) patients having the most and least CPM use. Age-adjusted CPM use was significantly higher for ER+/PR+ tumors than ER-/PR- ones for each race/ethnicity group among patients with mastectomy. However, among patients with any breast surgeries, the only difference was a higher proportion of CPM use for ER-/PR- tumors (8.6%) than ER+/PR+ tumors (8.0%) in non-Hispanic Whites. CPM use has increased over time in all racial/ethnic groups despite ER/PR status. CONCLUSION: CPM usage was lower not only in non-Hispanic Blacks, but also in non-Hispanic API and Hispanic patients compared to non-Hispanic White patients. CPM usage tended to be higher for ER+/PR+ tumors, but the results varied when different denominators (all mastectomies vs. all breast surgeries) were used. PMID- 26999401 TI - Population-level cure of colorectal cancer in Malta: An analysis of patients diagnosed between 1995 and 2004. AB - AIM: The aim of this study was to estimate the population-level 'cure' of Maltese colorectal cancer patients diagnosed between 1995 and 2004, and to estimate the median survival time for the 'uncured' patients. METHODS AND STUDY POPULATION: Analysis was conducted on 1470 cases registered by the Malta National Cancer Register between 1995 and 2004 and followed up to end of 2010. The mean age of the patients was 66.4 (95%CI 65.8-67.1), and the number of men and women were equal. Background mortality for 1995-2010 was extracted from publicly available life tables. A mixture model with Weibull survival distribution and identity link was used to model 'cure'. RESULTS: The overall 'cured' proportion for the patients diagnosed in 1995-1999 was 45.3% (95%CI 40.2-50.5) while the 'cured' proportion for the patients diagnosed in 2000-2004 was 52.3% (95%CI 47.2-57.5). Median survival time for the 'uncured' patients increased in the second calendar period from 1.25 years (95%CI 1.04-1.45) to 1.42 years (95%CI 1.15-1.76). CONCLUSION: In Malta, as in the rest of Europe, improvements have been made in short- and long-term survival over the 15-year period under study. To continue this improvement, differences by age that still persist must be investigated and efforts focused to reduce any gaps between Malta and other European countries. PMID- 26999392 TI - The Structure and Function of Type III Secretion Systems. AB - Type III secretion systems (T3SSs) afford Gram-negative bacteria an intimate means of altering the biology of their eukaryotic hosts--the direct delivery of effector proteins from the bacterial cytoplasm to that of the eukaryote. This incredible biophysical feat is accomplished by nanosyringe "injectisomes," which form a conduit across the three plasma membranes, peptidoglycan layer, and extracellular space that form a barrier to the direct delivery of proteins from bacterium to host. The focus of this chapter is T3SS function at the structural level; we will summarize the core findings that have shaped our understanding of the structure and function of these systems and highlight recent developments in the field. In turn, we describe the T3SS secretory apparatus, consider its engagement with secretion substrates, and discuss the posttranslational regulation of secretory function. Lastly, we close with a discussion of the future prospects for the interrogation of structure-function relationships in the T3SS. PMID- 26999397 TI - Epidemiology and Virulence of Klebsiella pneumoniae. AB - Strains of Klebsiella pneumoniae are frequently opportunistic pathogens implicated in urinary tract and catheter-associated urinary-tract infections of hospitalized patients and compromised individuals. Infections are particularly difficult to treat since most clinical isolates exhibit resistance to several antibiotics leading to treatment failure and the possibility of systemic dissemination. Infections of medical devices such as urinary catheters is a major site of K. pneumoniae infections and has been suggested to involve the formation of biofilms on these surfaces. Over the last decade there has been an increase in research activity designed to investigate the pathogenesis of K. pneumoniae in the urinary tract. These investigations have begun to define the bacterial factors that contribute to growth and biofilm formation. Several virulence factors have been demonstrated to mediate K. pneumoniae infectivity and include, but are most likely not limited to, adherence factors, capsule production, lipopolysaccharide presence, and siderophore activity. The development of both in vitro and in vivo models of infection will lead to further elucidation of the molecular pathogenesis of K. pneumoniae. As for most opportunistic infections, the role of host factors as well as bacterial traits are crucial in determining the outcome of infections. In addition, multidrug-resistant strains of these bacteria have become a serious problem in the treatment of Klebsiella infections and novel strategies to prevent and inhibit bacterial growth need to be developed. Overall, the frequency, significance, and morbidity associated with K. pneumoniae urinary tract infections have increased over many years. The emergence of these bacteria as sources of antibiotic resistance and pathogens of the urinary tract present a challenging problem for the clinician in terms of management and treatment of individuals. PMID- 26999402 TI - Carbamazepine-related antiepileptic drugs for the treatment of epilepsy - a comparative review. PMID- 26999408 TI - Development of a Yellow Flag Assessment Tool for Orthopaedic Physical Therapists: Results From the Optimal Screening for Prediction of Referral and Outcome (OSPRO) Cohort. AB - Study Design Clinical measurement, cross-sectional. Background Pain-associated psychological distress adversely influences outcomes for patients with musculoskeletal pain. However, assessment of pain-associated psychological distress (ie, yellow flags) is not routinely performed in orthopaedic physical therapy practice. A standardized yellow flag assessment tool will better inform treatment decision making related to psychologically informed practice. Objectives To describe the development of a concise, multidimensional yellow flag assessment tool for application in orthopaedic physical therapy clinical practice. Methods A 136-item yellow flag item bank was developed from validated psychological questionnaires across domains related to pain vulnerability (negative mood, fear avoidance) and resilience (positive affect/coping). Patients seeking physical therapy with neck, back, knee, or shoulder pain completed the item bank. Iterative statistical analyses determined minimal item sets meeting thresholds for identifying elevated vulnerability or low resilience (ie, upper or lower quartile, as indicated). Further item reduction yielded a concise yellow flag assessment tool to assess 11 psychological constructs measuring pain associated psychological distress. Correlations between the assessment tool and individual psychological questionnaires were measured and compared between anatomical regions. Concurrent validity was assessed by determining variance explained in pain and disability scores by the assessment tool. Results Subjects with elevated vulnerability and decreased resilience were identified with a high degree of accuracy (minimum of 85%) using a 17-item tool. Correlations were moderate to high between the 17-item tool and individual psychological questionnaires, with no significant differences in correlations between different anatomical regions. Shorter 10- and 7-item versions of the assessment tool allow clinicians the flexibility to assess for yellow flags quickly with acceptable trade-offs in accuracy (81% and 75%, respectively). All versions of the tool explained significant additional variance in pain and disability scores (range, 19.3%-36.7%) after accounting for demographics, historical variables, and anatomical region of pain. Conclusion Concise assessment of yellow flags is feasible in outpatient physical therapy settings. This multidimensional tool advances assessment of pain-associated psychological distress through the addition of positive affect/coping constructs and estimation of full questionnaire scores. Further study is warranted to determine how this tool complements established risk-assessment tools by providing the option for efficient treatment monitoring. J Orthop Sports Phys Ther 2016;46(5):327-345. Epub 21 Mar 2016. doi:10.2519/jospt.2016.6487. PMID- 26999395 TI - Bacterial Secretion Systems: An Overview. AB - Bacterial pathogens utilize a multitude of methods to invade mammalian hosts, damage tissue sites, and thwart the immune system from responding. One essential component of these strategies for many bacterial pathogens is the secretion of proteins across phospholipid membranes. Secreted proteins can play many roles in promoting bacterial virulence, from enhancing attachment to eukaryotic cells, to scavenging resources in an environmental niche, to directly intoxicating target cells and disrupting their functions. Many pathogens use dedicated protein secretion systems to secrete virulence factors from the cytosol of the bacteria into host cells or the host environment. In general, bacterial protein secretion apparatuses can be divided into classes, based on their structures, functions, and specificity. Some systems are conserved in all classes of bacteria and secrete a broad array of substrates, while others are only found in a small number of bacterial species and/or are specific to only one or a few proteins. In this chapter, we review the canonical features of several common bacterial protein secretion systems, as well as their roles in promoting the virulence of bacterial pathogens. Additionally, we address recent findings that indicate that the innate immune system of the host can detect and respond to the presence of protein secretion systems during mammalian infection. PMID- 26999404 TI - A national survey of thromboprophylaxis in traumatic brain injury in the United Kingdom. AB - INTRODUCTION: Patients with traumatic brain injury (TBI) are at increased risk of venous thromboembolic events (VTE). In this survey, we aimed to assess current practice in the United Kingdom and identify areas of variation for further investigation. METHODS: We distributed a case-based survey to neurosurgical consultants and trainees via e-mail. The survey included four index TBI cases commonly seen: a surgically treated acute extradural haematoma, bilateral frontal contusions treated conservatively, diffuse axonal injury requiring critical care and a conservatively managed small acute subdural haematoma. Each case vignette included questions looking at a range of areas regarding thromboprophylaxis. RESULTS: Sixty-two responses were collected among UK neurosurgeons with a good geographic distribution. In each case, over 90% of respondents would initiate mechanical prophylaxis (MTP) at admission. There was greater variation on the decision to commence pharmacological prophylaxis (PTP). Consultants showed a higher willing to commence PTP across all cases (84%) compared to trainees (77.4%). Low molecular weight heparin (LMWH) was the favoured PTP agent in over 90% of respondents. There was significant variability in the timing of initiation of PTP within and between cases. The median times to commence PTP across all four cases ranged from 1 to 7 days. CONCLUSION: This survey highlighted broad consensus on the use of MTP and choice of PTP agent, when used. However, the survey also demonstrated wide intra-case variation on whether to start PTP and particularly the timing of initiation. This discordance in practice shines light on the lack of evidence guiding thromboprophyalxis in TBI and adds weight to the need for prospective randomised trials to guide clinical management. PMID- 26999399 TI - Evolution of Bacterial Pathogens Within the Human Host. AB - Selective pressures within the human host, including interactions with innate and adaptive immune responses, exposure to medical interventions such as antibiotics, and competition with commensal microbiota all facilitate the evolution of bacterial pathogens. In this chapter, we present examples of pathogen strategies that emerged as a result of selective pressures within the human host niche and discuss the resulting coevolutionary "arms race" between these organisms. In bacterial pathogens, many of the genes responsible for these strategies are encoded on mobile pathogenicity islands or plasmids, underscoring the importance of horizontal gene transfer in the emergence of virulent microbial species. PMID- 26999407 TI - Plasma engineered surfaces for orthopedic devices. AB - Atmospheric pressure plasma was used to graft various biocompatible polymers to the surface of ultra-high molecular weight polyethylene (UHMWPE). Polymers used as grafts in this study were poly(2-hydroxyethylmethacrylate) (PHEMA) and polyethylene glycol (PEG). A significant decrease in contact angle was noted for grafted surfaces, indicating increased hydrophilicity. Surface functionalities were verified using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The wear properties of the coatings were determined by weight loss under conditions of a random motion pin-on-plate apparatus with the coated polyethylene plaques immersed in DI water. Based on these tests, the grafted surfaces exhibited an improved resistance to wear, compared to UHMWPE. Cell viability studies were used to confirm that the plasma treatment had no negative effects on the surface bio-toxicity. Based on the results, it is anticipated that the incorporation of these biocompatible polymer-grafted UHMWPE surfaces in metal-on-plastic orthopedic implants should improve their performance and longevity. PMID- 26999405 TI - Association of Sleep Deprivation With Reduction in Insulin Sensitivity as Assessed by the Hyperglycemic Clamp Technique in Adolescents. AB - IMPORTANCE: The association between short sleep duration and decreased insulin sensitivity in adolescents has been described. However, to our knowledge, no studies have investigated this association measuring insulin sensitivity by the hyperglycemic clamp technique. OBJECTIVES: To compare the distributions of parameters of insulin resistance in adolescents with sleep deprivation vs adequate sleep, and to investigate the association between sleep deprivation and insulin sensitivity. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional multicenter study using data from the Brazilian Metabolic Syndrome Study conducted from June 29, 2011, to December 3, 2014, at an obesity outpatient clinic at the University of Campinas and public schools, with a convenience sample of 615 adolescents aged 10 to 19.9 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for age and sex at the fifth percentile or higher. A subsample of 81 adolescents underwent the hyperglycemic clamp technique. MAIN OUTCOMES AND MEASURES: The self reported sleep duration was used to classify the population into 2 groups: adolescents with sleep deprivation (<8 hours/night) and adolescents with adequate sleep (>=8 hours/night). Insulin sensitivity was assessed using the hyperglycemic clamp technique. RESULTS: Among the 615 adolescents (56.3% female; median age, 15.9 years [interquartile range, 12.9-17.8 years]) included in the sample, the mean (SD) sleep duration was 7.9 (1.7) hours/night. The adolescents with sleep deprivation (n = 257) compared with those with adequate sleep (n = 358) had a higher median (interquartile range) age (17.0 [15.4-18.3] vs 14.1 [11.8-16.9] years), BMI (25.0 [21.2-29.3] vs 23.1 [19.5-27.6]), waist circumference (83.0 [73.5-95.4] vs 79.0 [68.5-91.0] cm), sagittal abdominal diameter (17.9 [15.8 20.8] vs 17.0 [15.0-19.8] cm), neck circumference (35.2 [33.0-38.0] vs 33.0 [30.0 35.5] cm), uric acid level (4.9 [4.0-5.8] vs 4.5 [3.7-5.5] mg/dL), and white blood cell count (7000 [5900-8200] vs 6600 [5600-7800] cells/MUL) (all P < .05). Moreover, the adolescents with sleep deprivation had a lower median (interquartile range) insulin sensitivity index compared with those with adequate sleep (0.10 [0.05-0.21] vs 0.21 [0.09-0.33] mg . kgfat-free mass-1 . min-1 . mU/L * 100, respectively; difference, -0.01; 95% CI, -0.01 to -0.00; P = .02). After controlling for age and sex in the multivariate regression model, sleep deprivation remained an independent predictor for those variables. In the sleep deprivation group, BMI and central distribution of fat were higher in all categories of adiposity. CONCLUSIONS AND RELEVANCE: Sleep deprivation (<8 hours of sleep per night) is associated with centripetal distribution of fat and decreased insulin sensitivity in adolescents. Therefore, investigations of sleep duration and sleep quality in adolescents should be included in clinical practice to promote, through health education, the eradication of the health risks associated with sleep restriction. PMID- 26999387 TI - Antigenic Variation in Bacterial Pathogens. AB - Antigenic variation is a strategy used by a broad diversity of microbial pathogens to persist within the mammalian host. Whereas viruses make use of a minimal proofreading capacity combined with large amounts of progeny to use random mutation for variant generation, antigenically variant bacteria have evolved mechanisms which use a stable genome, which aids in protecting the fitness of the progeny. Here, three well-characterized and highly antigenically variant bacterial pathogens are discussed: Anaplasma, Borrelia, and Neisseria. These three pathogens display a variety of mechanisms used to create the structural and antigenic variation needed for immune escape and long-term persistence. Intrahost antigenic variation is the focus; however, the role of these immune escape mechanisms at the population level is also presented. PMID- 26999410 TI - Altered Multifidus Recruitment During Walking in Young Asymptomatic Individuals With a History of Low Back Pain. AB - Study Design Controlled laboratory study, with a case-control, cross-sectional design. Background Individuals with low back pain have impaired activation of the multifidus during postural adjustments and increased activity of the erector spinae musculature during walking. However, it is unclear whether these alterations in muscle activity are evident during locomotion in individuals with a history of low back pain when they are between symptomatic episodes. Objectives To compare paraspinal muscle activity in young, healthy individuals and young individuals with a history of low back pain during walking turns. Methods Fourteen asymptomatic individuals with a history of low back pain and 14 controls performed 90 degrees walking turns at both a self-selected speed and a fast speed. The duration and amplitude of activity in the deep fibers of the multifidus and the lumbar and thoracic longissimus were quantified using intramuscular electromyography. Results There was a significant speed-by-group interaction for the duration of multifidus activity (P = .013). Duration of activity increased from the self-selected speed to the fast locomotor speed in the controls, but decreased in the individuals with a history of low back pain (P = .003). Self-selected speed was the same in both groups (P = .719). There was a trend toward a significant association between group and the direction of change in the duration of deep multifidus activity (chi(2) = 0.058). Duration of thoracic longissimus activity and amplitude of multifidus and thoracic longissimus activity increased similarly in both groups from the self-selected to the faster speed. Conclusion Even between symptomatic episodes, young individuals with a history of low back pain demonstrated altered recruitment of the deep fibers of the lumbar multifidus in response to changing locomotor speed during walking turns. J Orthop Sports Phys Ther 2016;46(5):365-374. Epub 21 Mar 2016. doi:10.2519/jospt.2016.6230. PMID- 26999406 TI - Relating Hearing Aid Use to Social and Emotional Loneliness in Older Adults. AB - PURPOSE: Hearing loss is a risk factor for social isolation and loneliness. We investigated the buffering effects of hearing aid use on perceived social and emotional loneliness. METHOD: Forty older adults participated. Prior to and following the hearing aid fitting, participants completed the De Jong Gierveld Loneliness Scale (De Jong Gierveld & Kamphuis, 1985); a change in feelings of loneliness following hearing aid use was the outcome indicator. RESULTS: There was a significant decline in perceptions of loneliness following 4 to 6 weeks of hearing aid use. A dose effect emerged with persons with moderate-to-severe hearing loss experiencing the greatest reduction in perceived loneliness with hearing aid use. CONCLUSION: Associated with poorer health status and higher consumption of health care services, perceived loneliness is a challenge to treat. Hearing aid use appears to be a buffer against the experience of loneliness. PMID- 26999409 TI - Cross-cultural Adaptation and Validation of the Victorian Institute of Sport Assessment-Patella Questionnaire for French-Speaking Patients With Patellar Tendinopathy. AB - Study Design Clinical measurement study. Background The Victorian Institute of Sport Assessment-Patella (VISA-P), originally developed in English, assesses the severity of patellar tendinopathy symptoms. To date, no French version of the questionnaire exists. Objectives The aim of our study was to translate the VISA-P into French and verify its psychometric properties. Methods The translation and cultural adaptation were performed according to international recommendations in 6 steps: initial translation, translation merging, back translation to the original language, use of an expert committee to reach a prefinal version, test of the prefinal version, and expert committee appraisal of a final version. Afterward, the psychometric properties of the final French version (VISA-PF) were assessed in 92 subjects, divided into 3 groups: pathological subjects (n = 28), asymptomatic subjects (n = 22), and sports-risk subjects (n = 42). Results All members of the expert committee agreed with the final version. On a scale ranging from 0 to 100, with 100 representing an asymptomatic subject, the average +/- SD scores on the VISA-PF were 53 +/- 17 for the pathological group, 99 +/- 2 for the healthy group, and 86 +/- 14 for the sports-risk group. The test-retest reliability of the VISA-PF was excellent, with good internal consistency. Correlations between the VISA-PF and divergent validity of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were low, and the correlation coefficient values measured between the VISA-PF scores and converged items of the SF-36 were higher. Conclusion The VISA-PF is understandable, valid, and suitable for French-speaking patients with patellar tendinopathy. J Orthop Sports Phys Ther 2016;46(5):384-390. Epub 21 Mar 2016. doi:10.2519/jospt.2016.5937. PMID- 26999411 TI - Comparing the Predictive Value of Task Performance and Task-Specific Sensitivity During Physical Function Testing Among People With Knee Osteoarthritis. AB - Study Design Cross-sectional cohort. Background Knee osteoarthritis (OA) is a leading cause of pain and mobility restriction. Past research has advocated the use of brief, functional tasks to evaluate these restrictions, such as the six minute-walk test and the timed up-and-go test. Typically, only task performance (ie, walking distance, completion time) is used to inform clinical practice. Recent research, however, suggests that individual variance in how people feel while completing these tasks (ie, task sensitivity) might also have important clinical value. Objective To compare the predictive value of task performance and task-specific sensitivity in determining OA-related physical function (measured by the Western Ontario and McMaster Universities Osteoarthritis Index) and pain related interference (measured by the Multidimensional Pain Inventory). Methods One hundred eight participants with chronic knee OA completed the six-minute-walk test and the timed up-and-go test, and reported levels of discomfort and affective response (mood) associated with each test. Results In separate regression models, both task performance and task-specific sensitivity predicted OA-related physical function and pain-related interference. A final regression model including all significant predictors showed that task-specific sensitivity (specifically, post-six-minute-walk discomfort) emerged as a unique predictor of both outcomes. Conclusion These findings highlight the value of a novel clinical assessment strategy for patients with knee OA. While clinicians commonly focus on how patients perform on standardized functional tasks, these results highlight the value of also considering levels of posttask sensitivity. Measures of task specific sensitivity relate to Maitland's concept of pain irritability, which may be a useful framework for future research on sensitizing factors and pain-related disability. J Orthop Sports Phys Ther 2016;46(5):346-356. Epub 21 Mar 2016. doi:10.2519/jospt.2016.6311. PMID- 26999413 TI - Prevalence of face recognition deficits in middle childhood. AB - Approximately 2-2.5% of the adult population is believed to show severe difficulties with face recognition, in the absence of any neurological injury-a condition known as developmental prosopagnosia (DP). However, to date no research has attempted to estimate the prevalence of face recognition deficits in children, possibly because there are very few child-friendly, well-validated tests of face recognition. In the current study, we examined face and object recognition in a group of primary school children (aged 5-11 years), to establish whether our tests were suitable for children and to provide an estimate of face recognition difficulties in children. In Experiment 1 (n = 184), children completed a pre-existing test of child face memory, the Cambridge Face Memory Test-Kids (CFMT-K), and a bicycle test with the same format. In Experiment 2 (n = 413), children completed three-alternative forced-choice matching tasks with faces and bicycles. All tests showed good psychometric properties. The face and bicycle tests were well matched for difficulty and showed a similar developmental trajectory. Neither the memory nor the matching tests were suitable to detect impairments in the youngest groups of children, but both tests appear suitable to screen for face recognition problems in middle childhood. In the current sample, 1.2-5.2% of children showed difficulties with face recognition; 1.2-4% showed face-specific difficulties-that is, poor face recognition with typical object recognition abilities. This is somewhat higher than previous adult estimates: It is possible that face matching tests overestimate the prevalence of face recognition difficulties in children; alternatively, some children may "outgrow" face recognition difficulties. PMID- 26999394 TI - Contrasting Lifestyles Within the Host Cell. AB - Intracellular bacterial pathogens have evolved to exploit the protected niche provided within the boundaries of a eukaryotic host cell. Upon entering a host cell, some bacteria can evade the adaptive immune response of its host and replicate in a relatively nutrient-rich environment devoid of competition from other host flora. Growth within a host cell is not without their hazards, however. Many pathogens enter their hosts through receptor-mediated endocytosis or phagocytosis, two intracellular trafficking pathways that terminate in a highly degradative organelle, the phagolysosome. This usually deadly compartment is maintained at a low pH and contains degradative enzymes and reactive oxygen species, resulting in an environment to which few bacterial species are adapted. Some intracellular pathogens, such as Shigella, Listeria, Francisella, and Rickettsia, escape the phagosome to replicate within the cytosol of the host cell. Bacteria that remain within a vacuole either alter the trafficking of their initial phagosomal compartment or adapt to survive within the harsh environment it will soon become. In this chapter, we focus on the mechanisms by which different vacuolar pathogens either evade lysosomal fusion, as in the case of Mycobacterium and Chlamydia, or allow interaction with lysosomes to varying degrees, such as Brucella and Coxiella, and their specific adaptations to inhabit a replicative niche. PMID- 26999412 TI - Dynamic Single-Leg Postural Control Is Impaired Bilaterally Following Anterior Cruciate Ligament Reconstruction: Implications for Reinjury Risk. AB - Study Design Cross-sectional, controlled laboratory study. Background Postural control following anterior cruciate ligament reconstruction (ACLR) primarily has been investigated during static single-leg balance tasks. Little is known about dynamic postural control deficits post-ACLR. Objectives To compare dynamic postural control (bilaterally) in individuals who have undergone ACLR and in healthy controls, and to evaluate the relationship between dynamic postural control and self-reported and objective function. Methods Ninety-seven participants (66 male; median age, 28 years) 12 months post-ACLR and 48 healthy controls (20 male; median age, 30 years) underwent balance assessment using a Nintendo Wii Balance Board during a single-leg squat. Center-of-pressure (CoP) path velocity, as well as CoP amplitude and standard deviation, in both mediolateral (ML) and anteroposterior (AP) directions were recorded. Self reported function was assessed with the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), while hop for distance was used to evaluate functional status. Results Compared to healthy controls, the ACLR group had greater mean CoP path velocity (16% higher, P = .004), ML range (23%, P<.001), ML SD (28%, P<.001), AP range (14%, P = .009), and AP SD (15%, P = .013), indicating worse dynamic balance post-ACLR. Dynamic balance performance was similar between the ACLR limb and the uninjured contralateral limb. The AP SD was weakly associated with hop performance (beta = -.2, P = .046); no balance measures were associated with IKDC score. Conclusion Individuals who have undergone ACLR demonstrate impaired dynamic balance bilaterally when performing a single-leg squat, which may have implications for physical function and future injury risk. Routine dynamic balance assessment may help identify patients who could benefit from targeted neuromuscular training programs to improve objective function and potentially lower reinjury risk. J Orthop Sports Phys Ther 2016;46(5):357-364. Epub 21 Mar 2016. doi:10.2519/jospt.2016.6305. PMID- 26999414 TI - Medicolegal-Malpractice and Ethical Issues in Radiology. PMID- 26999415 TI - Re: ISPRM discussion paper: Proposing dimensions for an international classification sytem for service organization in health-related rehabilitation. PMID- 26999391 TI - Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections. AB - Urinary tract infections (UTI) are among the most common bacterial infections in humans, affecting millions of people every year. UTI cause significant morbidity in women throughout their lifespan, in infant boys, in older men, in individuals with underlying urinary tract abnormalities, and in those that require long-term urethral catheterization, such as patients with spinal cord injuries or incapacitated individuals living in nursing homes. Serious sequelae include frequent recurrences, pyelonephritis with sepsis, renal damage in young children, pre-term birth, and complications of frequent antimicrobial use including high level antibiotic resistance and Clostridium difficile colitis. Uropathogenic E. coli (UPEC) cause the vast majority of UTI, but less common pathogens such as Enterococcus faecalis and other enterococci frequently take advantage of an abnormal or catheterized urinary tract to cause opportunistic infections. While antibiotic therapy has historically been very successful in controlling UTI, the high rate of recurrence remains a major problem, and many individuals suffer from chronically recurring UTI, requiring long-term prophylactic antibiotic regimens to prevent recurrent UTI. Furthermore, the global emergence of multi-drug resistant UPEC in the past ten years spotlights the need for alternative therapeutic and preventative strategies to combat UTI, including anti-infective drug therapies and vaccines. In this chapter, we review recent advances in the field of UTI pathogenesis, with an emphasis on the identification of promising drug and vaccine targets. We then discuss the development of new UTI drugs and vaccines, highlighting the challenges these approaches face and the need for a greater understanding of urinary tract mucosal immunity. PMID- 26999396 TI - Bacterial Evasion of Host Antimicrobial Peptide Defenses. AB - Antimicrobial peptides (AMPs), also known as host defense peptides, are small naturally occurring microbicidal molecules produced by the host innate immune response that function as a first line of defense to kill pathogenic microorganisms by inducing deleterious cell membrane damage. AMPs also possess signaling and chemoattractant activities and can modulate the innate immune response to enhance protective immunity or suppress inflammation. Human pathogens have evolved defense molecules and strategies to counter and survive the AMPs released by host immune cells such as neutrophils and macrophages. Here, we review the various mechanisms used by human bacterial pathogens to resist AMP mediated killing, including surface charge modification, active efflux, alteration of membrane fluidity, inactivation by proteolytic digestion, and entrapment by surface proteins and polysaccharides. Enhanced understanding of AMP resistance at the molecular level may offer insight into the mechanisms of bacterial pathogenesis and augment the discovery of novel therapeutic targets and drug design for the treatment of recalcitrant multidrug-resistant bacterial infections. PMID- 26999416 TI - Cross-border ties and Arab American mental health. AB - Due to increasing discrimination and marginalization, Arab Americans are at a greater risk for mental health disorders. Social networks that include ties to the country of origin could help promote mental well-being in the face of discrimination. The role of countries of origin in immigrant mental health receives little attention compared to adjustment in destination contexts. This study addresses this gap by analyzing the relationship between nativity, cross border ties, and psychological distress and happiness for Arab Americans living in the greater Detroit Metropolitan Area (N = 896). I expect that first generation Arab Americans will have more psychological distress compared to one and half, second, and third generations, and Arab Americans with more cross border ties will have less psychological distress and more happiness. Data come from the 2003 Detroit Arab American Study, which includes measures of nativity, cross-border ties--attitudes, social ties, media consumption, and community organizations, and the Kessler-10 scale of psychological distress and self reported happiness. Ordered logistic regression analyses suggest that psychological distress and happiness do not vary much by nativity alone. However, cross-border ties have both adverse and protective effects on psychological distress and happiness. For all generations of Arab Americans, cross-border attitudes and social ties are associated with greater odds of psychological distress and for first generation Arab Americans, media consumption is associated with greater odds of unhappiness. In contrast, for all generations, involvement in cross-border community organizations is associated with less psychological distress and for the third generation, positive cross-border attitudes are associated with higher odds of happiness. These findings show the complex relationship between cross-border ties and psychological distress and happiness for different generations of Arab Americans. PMID- 26999417 TI - IL-1beta at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two birds with one stone? AB - Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1beta in the pathogenesis of both the diseases, the efficacy of IL-1 blocking molecules in controlling these diseases, and will provide information suggesting that targeting IL-1beta, in patients affected by both RA and T2D, may be a promising therapeutic choice. PMID- 26999418 TI - Metastatic osteosarcoma: a challenging multidisciplinary treatment. AB - Osteosarcoma is the most common malignant bone tumor, currently treated with pre and postoperative chemotherapy in association with the surgical removal of the tumor. About 15-20% of patients have evidence of metastases at diagnosis, mostly in the lungs. Patients with metastatic disease still have a very poor prognosis, with approximately 20-30% of long-term survivors, as compared with 65-70% of patients with localized disease. The optimum management of these patients has not been standardized yet due to several patterns of metastatic disease harboring different prognosis. Complete surgical resection of all sites of disease is mandatory and predictive of survival. Patients with multiple sites of disease not amenable to complete surgery removal should be considered for innovative therapeutic approaches because of poor prognosis. PMID- 26999420 TI - Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus. AB - Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM. PMID- 26999419 TI - Brain-derived neurotrophic factor Val66met polymorphism and plasma levels in road traffic accident survivors. AB - BACKGROUND: Alterations in brain-derived neurotrophic factor (BDNF) expression and release may play a role in the pathogenesis of post-traumatic stress disorder (PTSD). DESIGN: This study evaluated road traffic accident (RTA) survivors to determine whether PTSD and trauma-related factors were associated with plasma BDNF levels and BDNF Val66Met carrier status following RTA exposure. METHODS: One hundred and twenty-three RTA survivors (mean age 33.2 years, SD = 10.6 years; 56.9% male) were assessed 10 (SD = 4.9) days after RTA exposure. Acute stress disorder (ASD), as assessed with the Acute Stress Disorder Scale, was present in 50 (42.0%) of the participants. Plasma BDNF levels were measured with enzyme linked immunosorbent assay and BDNF Val66Met genotyping was performed. PTSD, as assessed with the Clinician-Administered PTSD Scale, was present in 10 (10.8%) participants at 6 months follow-up. RESULTS: Neither BDNF Val66Met genotype nor plasma BDNF was significantly associated with the presence or severity of ASD or PTSD. Plasma BDNF levels were, however, significantly correlated with the lifetime number of trauma exposures. CONCLUSIONS: In RTA survivors, plasma BDNF levels increased with increasing number of prior trauma exposures. Plasma BDNF may, therefore, be a marker of trauma load. PMID- 26999422 TI - Using RNA as Molecular Code for Programming Cellular Function. AB - RNA is involved in a wide-range of important molecular processes in the cell, serving diverse functions: regulatory, enzymatic, and structural. Together with its ease and predictability of design, these properties can lead RNA to become a useful handle for biological engineers with which to control the cellular machinery. By modifying the many RNA links in cellular processes, it is possible to reprogram cells toward specific design goals. We propose that RNA can be viewed as a molecular programming language that, together with protein-based execution platforms, can be used to rewrite wide ranging aspects of cellular function. In this review, we catalogue developments in the use of RNA parts, methods, and associated computational models that have contributed to the programmability of biology. We discuss how RNA part repertoires have been combined to build complex genetic circuits, and review recent applications of RNA based parts and circuitry. We explore the future potential of RNA engineering and posit that RNA programmability is an important resource for firmly establishing an era of rationally designed synthetic biology. PMID- 26999421 TI - Characteristics of BCR-ABL kinase domain mutations in chronic myeloid leukemia from India: not just missense mutations but insertions and deletions are also associated with TKI resistance. AB - We document the characteristics of BCR-ABL kinase domain mutations (KDM) in the largest study from India comprising of 385 patients and demonstrate that more than half (51.9%) of these patients have detectable abnormalities in the KD both in adult and in pediatric chronic myelogenous leukemia (CML). These comprise singly occurring missense mutations (25.5%), polyclonal/compound point mutations (4.9%), and insertions/deletions (29.6%). Missense mutations were most commonly seen in the imatinib-binding region followed by the P-loop. The commonest mutation in our dataset was T315I. Other common missense mutations were Y253H, M244V, and F317L. A high prevalence of BCR-ABL exon7 deletion (p.R362fs*) was also seen (25.5% of the entire cohort), whereas the 35bpintron-derived insertion/truncation mutation detected in 12 patients. In the pediatric age group, 58.8% of patients harbored missense mutations, polyclonal/compound mutations as well as insertions and deletions. We detected 11 novel mutations (seven missense mutations and four insertions/deletions). PMID- 26999424 TI - Monoclonal gammopathy-associated pure red cell aplasia. AB - Pure red cell aplasia (PRCA) is a rare disorder characterized by inhibition of erythroid precursors in the bone marrow and normochromic, normocytic anaemia with reticulocytopenia. Among 51 PRCA patients, we identified 12 (24%) patients having monoclonal gammopathy, monoclonal gammopathy of undetermined significance or smouldering multiple myeloma, with presence of monoclonal protein or abnormal serum free light chains and atypical bone marrow features of clonal plasmacytosis, hypercellularity and fibrosis. Thus far, three patients treated with anti-myeloma based therapeutics have responded with reticulocyte recovery and clinical transfusion independence, suggesting plasma cells play a key role in the pathogenesis of this specific monoclonal gammopathy-associated PRCA. PMID- 26999425 TI - Modified lumbar artery perforator flaps for gluteal pressure sore reconstruction. AB - BACKGROUND: Gluteal perforator flaps (GPFs) are the most useful for gluteal region pressure sore reconstruction. However, application is difficult if the surrounding area has scar tissue from previous operations or trauma, especially with recurrent sores. We describe the use of modified lumbar artery perforator flaps when GPFs cannot be used. METHODS: Between May 2009 and April 2014, 51 patients underwent gluteal pressure sore reconstructions with gluteal (n = 39) or modified lumbar artery (n = 12) perforator flaps. Patients in the modified lumbar artery perforator group had scar tissue from trauma or previous surgery. In this retrospective review, we analyzed patient age and sex, defect size and location, operative time, follow-up duration, immediate postoperative issues, flap necrosis, dehiscence, re-operation, donor-site morbidity and recurrence. Complications and clinical outcomes were compared between groups. RESULTS: We found no significant differences in patient demographics, surgical complications or clinical outcomes. There were eight cases of temporary congestion (20.51%) and four of partial flap necrosis (10.25%) in the gluteal perforator group. In the modified lumbar artery perforator group, there were three cases of temporary congestion (25%) and one of partial flap necrosis (8.33%). No pressure sores recurred during follow-up in either group. CONCLUSION: GPFs are the gold standards for gluteal pressure sores, but modified lumbar artery perforator flaps are relatively easy and useful when GPFs cannot be used due to scar tissue. PMID- 26999426 TI - Disguising a Suicide as a Homicide: Sir Arthur Conan Doyle, Hans Gross, and "The Problem of Thor Bridge". PMID- 26999423 TI - Elastomeric free-form blood vessels for interconnecting organs on chip systems. AB - Conventional blood vessel-on-a-chip models are typically based on microchannel like structures enclosed within bulk elastomers such as polydimethylsiloxane (PDMS). However, these bulk vascular models largely function as individual platforms and exhibit limited flexibility particularly when used in conjunction with other organ modules. Oftentimes, lengthy connectors and/or tubes are still needed to interface multiple chips, resulting in a large waste volume counterintuitive to the miniaturized nature of organs-on-chips. In this work, we report the development of a novel form of a vascular module based on PDMS hollow tubes, which closely emulates the morphology and properties of human blood vessels to integrate multiple organs-on-chips. Specifically, we present two templating strategies to fabricate hollow PDMS tubes with adjustable diameters and wall thicknesses, where metal rods or airflow were employed as the inner templates, while plastic tubes were used as the outer template. The PDMS tubes could then be functionalized by human umbilical vein endothelial cells (HUVECs) in their interior surfaces to further construct elastomeric biomimetic blood vessels. The endothelium developed biofunctionality as demonstrated by the expression of an endothelial biomarker (CD31) as well as dose-dependent responses in the secretion of von Willebrand factor and nitric oxide upon treatment with pharmaceutical compounds. We believe that with their clear advantages including high optical transparency, gas permeability, and tunable elasticity matching those of native blood vessels, these free-form PDMS vascular modules can supplement bulk vascular organoids and likely replace inert plastic tubes in integrating multiple organoids into a single microfluidic circuitry. PMID- 26999427 TI - Establishing Standards for Side-by-Side Radiographic Comparisons. AB - The objectives of this research were to evaluate the use of various anatomical features that are visible in standard radiographs and to develop a standard system of assessing concordant features for making positive identifications through radiographic comparison.The radiographs used in the study include craniofacial (n = 41), chest (n = 100), and proximal femur (n = 49), which were made available by the North Carolina Office of the Chief Medical Examiner. Radiographs were scored for number of concordant features and were analyzed using classification decision trees. The accuracy of the classification tree models was evaluated using a receiver operating characteristic.Two or more points of concordance are required in lateral cranial radiographs for a 97% probability of a positive identification. If more than 1 concordant feature exists on the cervical vertebrae, there is a 99% probability of correct identification. For thoracic and lumbar vertebrae, 4 or more concordant features are required for a 98% probability of correct identification. If there are 1 or more femoral head and neck concordant features, the probability of a correct identification is 94% and 97%, respectively. This study established the minimum number of concordant areas needed to confirm positive identifications in 3 standard radiographic views. PMID- 26999428 TI - Mixed adenoneuroendocrine carcinoma (MANEC) of the gastroesophageal junction: a case report and review of the literature. AB - Esophageal cancer is the fourth most common neoplasm of the gastrointestinal tract. It is responsible for 1.7% of all deaths related with cancer. The two main types of esophageal cancer are squamous cell carcinoma and adenocarcinoma. Other types of esophageal cancer are uncommon. We present a 57-year-old man admitted to the hospital with nausea and vomiting due to a high-grade malignant mixed adenoneuroendocrine carcinoma of the gastroesophageal junction. The patient underwent Ivor-Lewis esophagectomy and adyuvant chemoradiotherapy. At 8-month follow-up he was alive without evidence of recurrence. PMID- 26999430 TI - Chemically Driven Interfacial Coupling in Charge-Transfer Mediated Functional Superstructures. AB - Organic charge-transfer superstructures are enabling new interfacial electronics, such as organic thermoelectrics, spin-charge converters, and solar cells. These carbon-based materials could also play an important role in spin-based electronics due to their exceptionally long spin lifetime. However, to explore these potentials a coherent design strategy to control interfacial charge transfer interaction is indispensable. Here we report that the control of organic crystallization and interfacial electron coupling are keys to dictate external stimuli responsive behaviors in organic charge-transfer superstructures. The integrated experimental and computational study reveals the importance of chemically driven interfacial coupling in organic charge-transfer superstructures. Such degree of engineering opens up a new route to develop a new generation of functional charge-transfer materials, enabling important advance in all organic interfacial electronics. PMID- 26999429 TI - Aesthetic closure of the donor site of a radial forearm free flap with two local curved skin grafts. AB - The authors have designed an aesthetic and effective coverage technique using local curved skin grafts along with vascular pedicles without additional skin incisions to solve the disadvantages of skin coverage problem of donor site defect after radial forearm free flap (RFFF) harvesting. This has, to the authors' knowledge, not been previously described. PMID- 26999431 TI - Copper Benzenetricarboxylate Metal-Organic Framework Nucleation Mechanisms on Metal Oxide Powders and Thin Films formed by Atomic Layer Deposition. AB - Chemically functional microporous metal-organic framework (MOF) crystals are attractive for filtration and gas storage applications, and recent results show that they can be immobilized on high surface area substrates, such as fiber mats. However, fundamental knowledge is still lacking regarding initial key reaction steps in thin film MOF nucleation and growth. We find that thin inorganic nucleation layers formed by atomic layer deposition (ALD) can promote solvothermal growth of copper benzenetricarboxylate MOF (Cu-BTC) on various substrate surfaces. The nature of the ALD material affects the MOF nucleation time, crystal size and morphology, and the resulting MOF surface area per unit mass. To understand MOF nucleation mechanisms, we investigate detailed Cu-BTC MOF nucleation behavior on metal oxide powders and Al2O3, ZnO, and TiO2 layers formed by ALD on polypropylene substrates. Studying both combined and sequential MOF reactant exposure conditions, we find that during solvothermal synthesis ALD metal oxides can react with the MOF metal precursor to form double hydroxy salts that can further convert to Cu-BTC MOF. The acidic organic linker can also etch or react with the surface to form MOF from an oxide metal source, which can also function as a nucleation agent for Cu-BTC in the mixed solvothermal solution. We discuss the implications of these results for better controlled thin film MOF nucleation and growth. PMID- 26999433 TI - Big Changes for Small Noncovalent Dimers: Revisiting the Potential Energy Surfaces of (P2)2 and (PCCP)2 with CCSD(T) Optimizations and Vibrational Frequencies. AB - This article details the re-examination of low-lying stationary points on the potential energy surfaces (PESs) of two challenging noncovalent homogeneous dimers, (P2)2 and (PCCP)2. The work was motivated by the rather large differences between MP2 and CCSD(T) energetics that were recently reported for these systems (J. Comput. Chem. 2014, 35, 479-487). The current investigation reveals significant qualitative and quantitative changes when the CCSD(T) method is used to characterize the stationary points instead of MP2. For example, CCSD(T) optimizations and harmonic vibrational frequency computations with the aug-cc pVTZ basis set indicate that the parallel-slipped (PS) structure is the only P2 dimer stationary point examined that is a minimum (zero imaginary frequencies, ni = 0), whereas prior MP2 computations indicated that it was a transition state (ni = 1). Furthermore, the L-shaped structure of (P2)2 was the only minimum according to MP2 computations, but it collapses to the PS structure on the CCSD(T)/aug-cc pVTZ PES. For the larger PCCP dimer, the CCSD(T) computations reveal that four rather than just two of the six stationary points characterized are minima. A series of explicitly correlated single-point energies were computed for all of the optimized structures to estimate the MP2 and CCSD(T) electronic energies at the complete basis set limit. CCSDT(Q) computations were also performed to assess the effects of dynamical electron correlation beyond the CCSD(T) level. For both (P2)2 and (PCCP)2, dispersion remains the dominant attractive component to the interaction energy according to symmetry-adapted perturbation theory analyses, and it is also the most challenging component to accurately evaluate. PMID- 26999432 TI - The pugilistDominant Mutation of Drosophila melanogaster: A Simple-Sequence Repeat Disorder Reveals Localized Transport in the Eye. AB - The pugilist-Dominant mutation results from fusion of a portion of the gene encoding the tri-functional Methylene Tetrahydrofolate Dehydrogenase (E.C.1.5.1.5, E.C.3.5.4.9, E.C.6.3.4.3) to approximately one kb of a heterochromatic satellite repeat. Expression of this fusion gene results in an unusual ring pattern of pigmentation around the eye. We carried out experiments to determine the mechanism for this pattern. By using FLP-mediated DNA mobilization to place different pugD transgenes at pre-selected sites we found that variation in repeat length makes a strong contribution to variability of the pug phenotype. This variation is manifest primarily as differences in the thickness of the pigmented ring. We show that similar phenotypic variation can also be achieved by changing gene copy number. We found that the pugD pattern is not controlled by wingless, which is normally expressed in a similar ring pattern. Finally, we found that physical injury to a pugD eye can lead to pigment deposition in parts of the eye that would not have been pigmented in the absence of injury. Our results are consistent with a model in which a metabolite vital for pigment formation is imported from the periphery of the eye, and pugD limits the extent of its transport towards the center of the eye, thus revealing the existence of a hitherto unknown mechanism of localized transport in the eye. PMID- 26999434 TI - Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD). AB - BACKGROUND: The immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD. METHODS: Serum samples were collected in incident PD cases and age-matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C-reactive protein were measured, with data reduction using principal-component analysis, and relationships between component scores and motor (MDS Unified Parkinson's Disease Rating Scale - part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated. RESULTS: TNF-alpha, IL1-beta, IL-2, and IL-10 were higher in PD (n = 230) than in controls (n = 93), P <= 0.001). Principal-component analysis of log-transformed data resulted in a 3-component solution explaining 51% of the variance. Higher "proinflammatory" and lower "anti-inflammatory" component scores were associated with more rapid motor progression over 36 months (P < 0.05), and higher "proinflammatory" component scores were associated with lower MMSE at all times (P < 0.05). Multiple linear regression analysis with adjustment for covariates confirmed "anti-inflammatory" component score was the strongest predictor of slower motor progression (beta = -0.22, P = 0.002), whereas proinflammatory cytokines were associated with lower baseline MMSE (beta = 0.175, P = 0.007). CONCLUSIONS: Serum immune marker profile is predictive of disease progression in PD and hence a potential prognostic biomarker. However, interventional trials are needed to clarify whether peripheral immune changes causally contribute to the progression of PD. (c) 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID- 26999436 TI - Rapid Identification of the Foodborne Pathogen Trichinella spp. by Matrix Assisted Laser Desorption/Ionization Mass Spectrometry. AB - Human trichinellosis occurs through consumption of raw or inadequately processed meat or meat products containing larvae of the parasitic nematodes of the genus Trichinella. Currently, nine species and three genotypes are recognized, of which T. spiralis, T. britovi and T. pseudospiralis have the highest public health relevance. To date, the differentiation of the larvae to the species and genotype level is based primarily on molecular methods, which can be relatively time consuming and labor intensive. Due to its rapidness and ease of use a matrix assisted laser desorption / ionization time of flight mass spectrometry (MALDI TOF MS) reference spectra database using Trichinella strains of all known species and genotypes was created. A formicacid/acetonitrile protein extraction was carried out after pooling 10 larvae of each Trichinella species and genotype. Each sample was spotted 9 times using alpha-cyano 4-hydoxy cinnamic acid matrix and a MicroFlex LT mass spectrometer was used to acquire 3 spectra (m/z 2000 to 20000 Da) from each spot resulting in 27 spectra/species or genotype. Following the spectra quality assessment, Biotyper software was used to create a main spectra library (MSP) representing nine species and three genotypes of Trichinella. The evaluation of the spectra generated by MALDI-TOF MS revealed a classification which was comparable to the results obtained by molecular methods. Also, each Trichinella species utilized in this study was distinct and distinguishable with a high confidence level. Further, different conservation methods such as freezing and conservation in alcohol and the host species origin of the isolated larvae did not have a significant influence on the generated spectra. Therefore, the described MALDI-TOF MS can successfully be implemented for both genus and species level identification and represents a major step forward in the use of this technique in foodborne parasitology. PMID- 26999437 TI - Novel Methodology for Rapid Detection of KRAS Mutation Using PNA-LNA Mediated Loop-Mediated Isothermal Amplification. AB - Detecting point mutation of human cancer cells quickly and accurately is gaining in importance for pathological diagnosis and choice of therapeutic approach. In the present study, we present novel methodology, peptide nucleic acid-locked nucleic acid mediated loop-mediated isothermal amplification (PNA-LNA mediated LAMP), for rapid detection of KRAS mutation using advantages of both artificial DNA and LAMP. PNA-LNA mediated LAMP reactions occurred under isothermal temperature conditions of with 4 primary primers set for the target regions on the KRAS gene, clamping PNA probe that was complimentary to the wild type sequence and LNA primers complementary to the mutated sequences. PNA-LNA mediated LAMP was applied for cDNA from 4 kinds of pancreatic carcinoma cell lines with or without KRAS point mutation. The amplified DNA products were verified by naked eye as well as a real-time PCR equipment. By PNA-LNA mediated LAMP, amplification of wild type KRAS DNA was blocked by clamping PNA probe, whereas, mutant type KRAS DNA was significantly amplified within 50 min. Mutant alleles could be detected in samples which diluted until 0.1% of mutant-to-wild type ratio. On the other hand, mutant alleles could be reproducibly with a mutant-to-wild type ratio of 30% by direct sequencing and of 1% by PNA-clamping PCR. The limit of detection (LOD) of PNA-LNA mediated LAMP was much lower than the other conventional methods. Competition of LNA clamping primers complementary to two different subtypes (G12D and G12V) of mutant KRAS gene indicated different amplification time depend on subtypes of mutant cDNA. PNA-LNA mediated LAMP is a simple, rapid, specific and sensitive methodology for the detection of KRAS mutation. PMID- 26999435 TI - Naturally Acquired Antibody Responses to Plasmodium vivax and Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) C-Terminal 19 kDa Domains in an Area of Unstable Malaria Transmission in Southeast Asia. AB - Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies. PMID- 26999438 TI - The indirect effects of childhood attention deficit hyperactivity disorder on alcohol problems in adulthood through unique facets of impulsivity. AB - BACKGROUND AND AIMS: Research has not studied unique impulsivity dimensions as prospective links between childhood attention deficit hyperactivity disorder (ADHD) and alcohol problems. We examined the association between childhood ADHD, five facets of impulsivity and alcohol problems in adulthood and the indirect effects of childhood ADHD-to-impulsivity-to-alcohol problems. DESIGN, SETTING AND PARTICIPANTS: Participants were from a longitudinal study (n = 289, meanage = 28.67) of individuals with (n = 170) and without (n = 119) childhood ADHD. The ADHD sample, as part of an ADHD summer treatment program, was diagnosed initially in childhood (1987-96, Pittsburgh, PA, USA) via structured parent interview and standardized parent/teacher ratings. The ADHD sample and demographically similar individuals without ADHD (living in the greater Pittsburgh area) were recruited to participate in the Pittsburgh ADHD Longitudinal Study (PALS) between 1999 and 2003. MEASUREMENTS: Self-reported impulsivity (UPPS-P) and alcohol-related problems were assessed in adulthood (2011-14). FINDINGS: Adults with, compared with those without, childhood ADHD had more alcohol problems (beta = 0.34, P < 0.05) and higher levels of negative urgency, positive urgency, lack of perseverance and lack of planning (betas = 0.24-0.31, Ps < 0.001). Impulsivity facets (except sensation-seeking) were related to number of alcohol problems (betas = 0.34-0.61, Ps < 0.05). Negative (beta = 0.26, P < 0.01) and positive (beta = 0.27, P < 0.01) urgency mediated the association between childhood ADHD and number of adult alcohol problems. CONCLUSIONS: Elevated levels of emotional impulsivity (negative/positive urgency) may place children with attention deficit hyperactivity disorder at increased risk for alcohol problems in adulthood. PMID- 26999439 TI - CsoR Is Essential for Maintaining Copper Homeostasis in Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis, a pathogen infecting one third of the world population, faces numerous challenges within the host, including high levels of copper. We have previously shown that M. tuberculosis CsoR is a copper inducible transcriptional regulator. Here we examined the hypothesis that csoR is necessary for maintaining copper homeostasis and surviving under various stress conditions. With an unmarked csoR knockout strain, we were able to characterize the role of csoR in M. tuberculosis as it faced copper and host stress. Growth under high levels of copper demonstrated that M. tuberculosis survives copper stress significantly better in the absence of csoR. Yet under minimal levels of copper, differential expression analysis revealed that the loss of csoR results in a cell wide hypoxia-type stress response with the induction of the DosR regulon. Despite the stress placed on M. tuberculosis by the loss of csoR, survival of the knockout strain was increased compared to wild type during the early chronic stages of mouse infection, suggesting that csoR could play an active role in modulating M. tuberculosis fitness within the host. Overall, analysis of CsoR provided an increased understanding of the M. tuberculosis copper response with implications for other intracellular pathogens harboring CsoR. PMID- 26999440 TI - Brief report: Benefit finding and identity processes in type 1 diabetes: Prospective associations throughout adolescence. AB - Identity formation constitutes a core developmental task during adolescence, but may be challenged when having a chronic illness such as type 1 diabetes. The present study examined whether viewing positive benefits to one's diabetes across adolescence was related to greater identity exploration and commitment later in time. A total of 55 adolescents (10-14 years; 47% female) with type 1 diabetes participated in a six-wave study spanning 3 years (with six-month measurement intervals). Through latent growth curve modeling, Time 6 identity scores were regressed on intercept and slope terms of benefit finding through Times 1-4, simultaneously controlling for demographic and clinical variables. Identity exploration (but not commitment) at Time 6 was positively predicted by the intercept and slope of benefit finding: adolescents who find benefits in diabetes are more inclined to explore different alternatives later on in adolescence. Benefit finding may constitute a resource facilitating identity formation in adolescents with diabetes. PMID- 26999441 TI - Conflict resolution patterns and violence perpetration in adolescent couples: A gender-sensitive mixed-methods approach. AB - This study used a sequential two-phase explanatory design. The first phase of this mixed-methods design aimed to explore conflict resolution strategies in adolescent dating couples, and the second phase to document, from both the perspective of the individual and of the couple, dyadic interaction patterns distinguishing youth inflicting dating violence from those who do not. A sample of 39 heterosexual couples (mean age 17.8 years) participated in semi-structured interviews and were observed during a 45 min dyadic interaction. At phase 1, qualitative analysis revealed three main types of conflict resolution strategies: 1) negotiating expectations and individual needs; 2) avoiding conflicts or their resolution; 3) imposing personal needs and rules through the use of violence. At phase 2, we focused on couples with conflictive patterns. Results indicate that couples who inflict violence differ from nonviolent couples by their tendency to experience conflicts when in disagreement and to resort to negative affects as a resolution strategy. In addition, while at an individual level, they show a tendency to withdraw from conflict and to use less positive affect, at a dyadic level they present less symmetry. Results offer important insights for prevention programs. PMID- 26999443 TI - Suicide After Evaluation for Involuntary Psychiatric Commitment-Who Gets Them and What Influences Survival Time? AB - Although involuntary psychiatric hospitalizations are associated with suicide risk, little is known about the relationship between evaluation for involuntary detention and suicide. We analyzed data on 10,082 suicides from 2000 to 2011 to examine demographics related to evaluation for detention and the association between demographics and evaluation dispositions on survival time. Evaluation preceded 11% of suicides; 53.8% of deaths occurred within 365 days, 6.5 times the expected rate. Males and older individuals were least likely to have been evaluated. Minority status and referral disposition influence 30-day survival time. Risk is highly concentrated in the first year following evaluation. PMID- 26999442 TI - Attachment anxiety predicts depression and anxiety symptoms following coronary artery bypass graft surgery. AB - OBJECTIVE: Depression and anxiety are associated with poor recovery in coronary artery bypass graft (CABG) patients, but little is known about predictors of depression and anxiety symptoms. DESIGN: We tested the prospective association between attachment orientation, and symptoms of depression and anxiety in CABG patients, 6-8 weeks, and 12 months following surgery. METHOD: One hundred and fifty-five patients who were undergoing planned CABG surgery were recruited. Patients completed questionnaires measuring attachment, depression, and anxiety prior to surgery, then 6-8 weeks, and 12 months after surgery. RESULTS: Attachment anxiety predicted symptoms of depression and anxiety at both follow-up time points, whereas attachment avoidance was not associated with depression or anxiety symptoms. The findings remained significant when controlling for baseline mood scores, social support, demographic, and clinical risk factors. CONCLUSION: These results suggest that attachment anxiety is associated with short-term and long-term depression and anxiety symptoms following CABG surgery. These results may offer important insight into understanding the recovery process in CABG surgery. Statement of contribution What is already known on this subject? Depression and anxiety symptoms are twice more likely to occur in coronary artery bypass graft (CABG) populations than in any other medical group. Depression and anxiety are associated with poor recovery following cardiac surgery. Predictors of depression and anxiety in CABG patients have been underexplored. What does this study add? This study highlights the importance of close interpersonal relationships on health. Attachment anxiety was prospectively associated with higher levels of depression and anxiety. These results add to understanding mechanisms linked to recovery following CABG. PMID- 26999444 TI - Unique Familial MLL(KMT2A)-Rearranged Precursor B-Cell Infant Acute Lymphoblastic Leukemia in Non-twin Siblings. AB - BACKGROUND: Infant acute lymphoblastic leukemia (ALL) has never occurred in families except for the ~100% concordant cases in monozygous twins attributed to twin-to-twin metastases. We report the first kindred with infant ALL in non-twin siblings. The siblings were diagnosed with MLL-rearranged (MLL-R) ALL 26 months apart. The second affected sibling had an unaffected dichorionic monozygous co twin. Both had fatal outcomes. PROCEDURES: Translocations were characterized by karyotype, FISH, multiplex FISH, and MLL breakpoint cluster region (bcr) Southern blot analysis. Breakpoint junctions and fusion transcripts were cloned by PCR. TP53 mutation and NADPH quinone oxidorecuctase 1 (NQO1) C609T analyses were performed, and pedigree history and parental occupations were ascertained. The likelihood of chance occurrence of infant ALL in non-twin siblings was computed based on a binomial distribution. Zygosity was determined by single nucleotide polymorphism (SNP) array. RESULTS: The translocations were not related or vertically transmitted. The complex karyotype of the proband's ALL had chromosome 2, 3, 4, and 11 abnormalities causing a 5'-MLL-AFF1-3' fusion and a non productive rearrangement of 3'MLL with a chromosome 3q intergenic region. The affected twin's ALL exhibited a simple t(4;11). The complex karyotype of the proband's ALL suggested a genotoxic insult, but no exposure was identified. There was no germline TP53 mutation. The NQO1 C609T risk allele was absent. The likelihood of infant ALL occurring in non-twin siblings by chance alone is one in 1.198 * 10(9) families. CONCLUSIONS: Whether because of a deleterious transplacental exposure, novel predisposition syndrome, or exceedingly rare chance occurrence, MLL-R infant ALL can occur in non-twin siblings. The discordant occurrence of infant ALL in the monozygous twins was likely because they were dichorionic. PMID- 26999445 TI - Spectroscopic (UV/VIS, Raman) and Electrophoresis Study of Cytosine-Guanine Oligonucleotide DNA Influenced by Magnetic Field. AB - Studying the effect of a magnetic field on oligonucleotide DNA can provide a novel DNA manipulation technique for potential application in bioengineering and medicine. In this work, the optical and electrochemical response of a 100 bases oligonucleotides DNA, cytosine-guanine (CG100), is investigated via exposure to different magnetic fields (250, 500, 750, and 1000 mT). As a result of the optical response of CG100 to the magnetic field, the ultra-violet-visible spectrum indicated a slight variation in the band gap of CG100 of about 0.3 eV. Raman spectroscopy showed a significant deviation in hydrogen and phosphate bonds' vibration after exposure to the magnetic field. Oligonucleotide DNA mobility was investigated in the external electric field using the gel electrophoresis technique, which revealed a small decrease in the migration of CG100 after exposure to the magnetic field. PMID- 26999446 TI - Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44 Dependent. AB - BACKGROUND: Although epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation. METHODS: Wild type (WT) and CD44 knock-out (KO) mice were exposed simultaneously to house dust mite (HDM) extract and CS. Inflammatory cells, hyaluronic acid (HA) and osteopontin (OPN) levels were measured in bronchoalveolar lavage fluid (BALF). Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th) 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures. RESULTS: In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice. CONCLUSION: We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44 dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics. PMID- 26999447 TI - Regionalization of browning revealed by whole subcutaneous adipose tissue imaging. AB - OBJECTIVE: White and brown adipose tissues play a major role in the regulation of metabolic functions. With the explosion of obesity and metabolic disorders, the interest in adipocyte biology is growing constantly. While several studies have demonstrated functional differences between adipose fat pads, especially in their involvement in metabolic diseases, there are no data available on possible heterogeneity within an adipose depot. METHODS: This study investigated the three dimensional (3-D) organization of the inguinal fat pad in adult mice by combining adipose tissue clearing and autofluorescence signal acquisition by confocal microscopy. In addition, the study analyzed the expression of genes involved in adipocyte biology and browning at the mARN and protein levels in distinct areas of the inguinal adipose tissue, in control conditions and after cold exposure. RESULTS: Semiautomated 3-D image analysis revealed an organization of the fat depot showing two regions: the core was structured into segmented lobules, whereas the periphery appeared unsegmented. Perilipin immunostaining showed that most of the adipocytes located in the core region had smaller lipid droplets, suggesting a brown-like phenotype. qPCR analysis showed a higher expression of the browning markers Ucp1, Prdm16, Ppargc1a, and Cidea in the core region than at the periphery. Finally, cold exposure induced upregulation of thermogenic gene expression associated with an increase of UCP1 protein, specifically in the core region of the inguinal fat depot. CONCLUSIONS: Altogether, these data demonstrate a structural and functional heterogeneity of the inguinal fat pad, with an anatomically restricted browning process in the core area. PMID- 26999448 TI - Serum tryptase concentration and progression to end-stage renal disease. AB - BACKGROUND: Mast cell activation can lead to nonclassical activation of the Renin Angiotensin-Aldosterone System. However, the relevance of this to human chronic kidney disease is unknown. We assessed the association between serum tryptase, a product of mast cell activation, and progression to end-stage renal disease or mortality in patients with advanced chronic kidney disease. We stratified patients by use of angiotensin-converting enzyme inhibitors/angiotensin receptor II blockers (ACEi/ARB). MATERIALS AND METHODS: This was a prospective cohort study of 446 participants recruited into the Renal Impairment in Secondary Care study. Serum tryptase was measured at recruitment by sandwich immunoassay. Cox regression analysis was undertaken to determine variables associated with progression to end-stage renal disease or death. RESULTS: Serum tryptase concentration was independently associated with progression to end-stage renal disease but not with death. In patients treated with ACEi or ARB, there was a strong independent association between higher tryptase concentrations and progression to end-stage renal disease; when compared to the lowest tertile, tryptase concentrations in the middle and highest tertiles had hazard ratios [HR] of 5.78 (95% confidence interval [CI] 1.19-28.03, P = 0.029) and 6.19 (95% CI 1.49-25.69, P = 0.012), respectively. The other independent risk factors for progression to end-stage renal disease were lower age, male gender, lower estimated glomerular filtration rate and higher urinary albumin creatinine ratio. CONCLUSION: Elevated serum tryptase concentration is an independent prognostic factor for progression to end-stage renal disease in patients with chronic kidney disease who are receiving treatment with an ACEi or ARB. PMID- 26999449 TI - SAFER, an Analysis Method of Quantitative Proteomic Data, Reveals New Interactors of the C. elegans Autophagic Protein LGG-1. AB - Affinity purifications followed by mass spectrometric analysis are used to identify protein-protein interactions. Because quantitative proteomic data are noisy, it is necessary to develop statistical methods to eliminate false positives and identify true partners. We present here a novel approach for filtering false interactors, named "SAFER" for mass Spectrometry data Analysis by Filtering of Experimental Replicates, which is based on the reproducibility of the replicates and the fold-change of the protein intensities between bait and control. To identify regulators or targets of autophagy, we characterized the interactors of LGG1, a ubiquitin-like protein involved in autophagosome formation in C. elegans. LGG-1 partners were purified by affinity, analyzed by nanoLC-MS/MS mass spectrometry, and quantified by a label-free proteomic approach based on the mass spectrometric signal intensity of peptide precursor ions. Because the selection of confident interactions depends on the method used for statistical analysis, we compared SAFER with several statistical tests and different scoring algorithms on this set of data. We show that SAFER recovers high-confidence interactors that have been ignored by the other methods and identified new candidates involved in the autophagy process. We further validated our method on a public data set and conclude that SAFER notably improves the identification of protein interactors. PMID- 26999450 TI - Management of iron overload before, during, and after hematopoietic stem cell transplantation for thalassemia major. AB - Solid evidence has established the negative impact of high iron burden and related tissue damage on the outcome of hemopoietic stem cell transplantation for thalassemia major. Recent improvements in our knowledge of iron metabolism have been focused on elevated non-transferrin-bound iron and labile plasma iron levels in the peritransplantation period as potential contributors to tissue toxicity and subsequent adverse transplant outcome. As mouse models have shown, iron overload can injure bone marrow hematopoiesis by increasing reactive oxygen species. The Pesaro experience, conducted in the deferoxamine-only era, clearly defined three iron-related factors (liver fibrosis, hepatomegaly, and quality of lifelong chelation) as significantly affecting transplant outcome. The detrimental effect of iron has only been clarified in recent years. Active interventional strategies are ongoing. Although successful hematopoietic stem cell transplantation clinically resolves the thalassemia marrow defect, patients still remain carriers of iron overload and of all the clinical complications acquired during prior years of transfusion therapy. Therefore, adequate "iron diagnosis" and management is mandatory after hemopoietic stem cell transplantation. In transplanted thalassemia patients, body iron should be returned to within the normal range. Phlebotomy is the gold standard to reduce iron burden; though deferoxamine is a proven, acceptable alternative, clinical investigations on deferasirox are ongoing. PMID- 26999451 TI - Templated Synthesis of Single-Walled Carbon Nanotubes with Specific Structure. AB - Single-walled carbon nanotubes (SWNTs) have shown great potential in various applications attributed to their unique structure-dependent properties. Therefore, the controlled preparation of chemically and structurally pristine SWNTs is a crucial issue for their advanced applications (e.g., nanoelectronics) and has been a great challenge for two decades. Epitaxial growth from well defined seeds has been shown to be a promising strategy to control the structure of SWNTs. Segments of carbon nanotubes, including short pipes from cutting of preformed nanotubes and caps from opening of fullerenes or cyclodehydrogenation of polycyclic hydrocarbon precursors, have been used as the seeds to grow SWNTs. Single-chirality SWNTs were obtained with both presorted chirality-pure SWNT segments and end caps obtained from polycyclic hydrocarbon molecules with designed structure. The main challenges of nanocarbon-segment-seeded processes are the stability of the seeds, yield, and efficiency. Catalyst-mediated SWNT growth is believed to be more efficient. The composition and morphology of the catalyst nanoparticles have been widely reported to affect the chirality distribution of SWNTs. However, chirality-specific SWNT growth is hard to achieve by alternating catalysts. The specificity of enzyme-catalyzed reactions brings us an awareness of the essentiality of a unique catalyst structure for the chirality selective growth of SWNTs. Only catalysts with the desired atomic arrangements in their crystal planes can act as structural templates for chirality-specific growth of SWNTs. We have developed a new family of catalysts, tungsten-based intermetallic compounds, which have high melting points and very special crystal structures, to facilitate the growth of SWNTs with designed chirality. By the use of W6Co7 catalysts, (12,6) SWNTs were directly grown with purity higher than 92%. Both high-resolution transmission electron microscopy measurements and density functional theory simulations show that the selective growth of (12,6) tubes is due to a good structural match between the carbon atom arrangement around the nanotube circumference and the metal atom arrangement of (0 0 12) planes in the catalyst. Similarly, (16,0) SWNTs exhibit a good structural match to the (116) planes of the W6Co7 catalyst. By optimization of the chemical vapor deposition (CVD) conditions, zigzag (16,0) SWNTs, which are generally known as a kinetically unfavorable species in CVD growth, were obtained with a purity of ~80%. Generally speaking, the chirality-specific growth of SWNTs is realized by the cooperation of two factors: the structural match between SWNTs and the catalysts makes the growth of SWNTs with specific chirality thermodynamically favorable, and further manipulation of the CVD conditions results in optimized growth kinetics for SWNTs with this designed chirality. We expect that this advanced epitaxial growth strategy will pave the way for the ultimate goal of chirality-specified growth of SWNTs and will also be applicable in the controlled preparation of other nanomaterials. PMID- 26999452 TI - An Energetic Guide for Estimating Trifluoromethyl Cation Donor Abilities of Electrophilic Trifluoromethylating Reagents: Computations of X-CF3 Bond Heterolytic Dissociation Enthalpies. AB - This work established an energetic guide for estimating the trifluoromethyl cation-donating abilities (TC(+)DA) of electrophilic trifluoromethylating reagents through computing X-CF3 bond (X = O, S, Se, Te, and I) heterolytic dissociation enthalpies. TC(+)DA values for a wide range of popular reagents were derived on the basis of density functional calculations (M06-2X). A good correspondence has been identified between the computed TC(+)DA values and the experimentally observed relative trifluoromethylating capabilities of the reagents. Substituent effects hold good linear free energy relationships on the TC(+)DAs of the most widely used reagents including Umemoto reagent, Yagupolskii Umemoto reagent, and Togni reagents, which allow their trifluoromethylating capabilities to be rationally tuned by substituents and thus extend their synthetic utility. All the information disclosed in this work would contribute to future rational exploration of the electrophilic trifluoromethylation chemistry. PMID- 26999453 TI - Letter to the Editor. PMID- 26999454 TI - Temporal Robustness of the Session Rating of Perceived Exertion. AB - PURPOSE: The session rating of perceived exertion (sRPE) has gained popularity as a "user friendly" method for evaluating internal training load. sRPE has historically been obtained 30 min after exercise. This study evaluated the effect of postexercise measurement time on sRPE after steady-state and interval cycle exercise. METHODS: Well-trained subjects (N = 15) (maximal oxygen consumption = 51 +/- 4 and 36 +/- 4 mL/kg [cycle ergometer] for men and women, respectively) completed counterbalanced 30-minute steady-state and interval training bouts. The steady-state ride was at 90% of ventilatory threshold. The work-to-rest ratio of the interval rides was 1:1, and the interval segment durations were 1, 2, and 3 min. The high-intensity component of each interval bout was 75% peak power output, which was accepted as a surrogate of the respiratory compensation threshold, critical power, or maximal lactate steady state. Heart rate, blood lactate, and rating of perceived exertion (RPE) were measured. The sRPE (category ratio scale) was measured at 5, 10, 15, 20, 25, 30, and 60 min and 24 h after each ride using a visual analog scale (VAS) to prevent bias associated with specific RPE verbal anchors. RESULTS: sRPE at 30 min postexercise followed a similar trend: steady state = 3.7, 1 min = 3.9, 2 min = 4.7, 3 min = 6.2. No significant differences (P > .05) in sRPE were found based on postexercise sampling times, from 5 min to 24 h postexercise. CONCLUSIONS: Postexercise time does not appear to have a significant effect on sRPE after either steady-state or interval exercise. Thus, sRPE appears to be temporally robust and is not necessarily limited to the 30-min-postexercise window historically used with this technique, although the presence or absence of a cooldown period after the exercise bout may be important. PMID- 26999456 TI - Targeting inhibition of Foxp3 by a CD28 2'-Fluro oligonucleotide aptamer conjugated to P60-peptide enhances active cancer immunotherapy. AB - The specific inhibition of Treg function has long been a major technical challenge in cancer immunotherapy. So far no single cell-surface marker has been identified that could be used to distinguish Treg cells from other lymphocytes. The only available specific marker mostly expressed in Treg is Foxp3, which is an intracellular transcription factor. A targeting molecule able to penetrate the membrane and inhibit Foxp3 within the cell is needed. P60-peptide is able to do that, but due to lack of target specificity, the doses are extremely high. In this study we have shown as a proof of concept that P60 Foxp3 inhibitor peptide can be conjugated with a CD28 targeting aptamer to deliver the peptide to CD28 expressing cells. The AptCD28-P60 construct is a clinically feasible reagent that improves the efficacy of the unconjugated P60 peptide very significantly. This approach was used to inhibit Treg function in a vaccination context, and it has shown a significant improvement in the induced immune response, entailing a lower tumor load in an antigen-specific cancer vaccine protocol. PMID- 26999455 TI - Fabrication of anatomically-shaped cartilage constructs using decellularized cartilage-derived matrix scaffolds. AB - The native extracellular matrix of cartilage contains entrapped growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potentially attractive biomaterial for cartilage tissue engineering. A limitation to this approach is that the native cartilage extracellular matrix possesses a pore size of only a few nanometers, which inhibits cellular infiltration. Efforts to increase the pore size of cartilage-derived matrix (CDM) scaffolds dramatically attenuate their mechanical properties, which makes them susceptible to cell-mediated contraction. In previous studies, we have demonstrated that collagen crosslinking techniques are capable of preventing cell-mediated contraction in CDM disks. In the current study, we investigated the effects of CDM concentration and pore architecture on the ability of CDM scaffolds to resist cell-mediated contraction. Increasing CDM concentration significantly increased scaffold mechanical properties, which played an important role in preventing contraction, and only the highest CDM concentration (11% w/w) was able to retain the original scaffold dimensions. However, the increase in CDM concentration led to a concomitant decrease in porosity and pore size. Generating a temperature gradient during the freezing process resulted in unidirectional freezing, which aligned the formation of ice crystals during the freezing process and in turn produced aligned pores in CDM scaffolds. These aligned pores increased the pore size of CDM scaffolds at all CDM concentrations, and greatly facilitated infiltration by mesenchymal stem cells (MSCs). These methods were used to fabricate of anatomically-relevant CDM hemispheres. CDM hemispheres with aligned pores supported uniform MSC infiltration and matrix deposition. Furthermore, these CDM hemispheres retained their original architecture and did not contract, warp, curl, or splay throughout the entire 28-day culture period. These findings demonstrate that given the appropriate fabrication parameters, CDM scaffolds are capable of maintaining complex structures that support MSC chondrogenesis. PMID- 26999457 TI - Nickel(II) Complexation with Nitrate in Dry [C4mim][Tf2N] Ionic Liquid: A Spectroscopic, Microcalorimetric, and Molecular Dynamics Study. AB - The complex formation of nitrate ions with nickel(II) in dry [C4mim][Tf2N] ionic liquid (IL) was investigated by means of UV-visible spectrophotometry, isothermal titration calorimetry (ITC), extended X-ray absorption fine structure spectroscopy (EXAFS), and molecular dynamics (MD) simulations. EXAFS spectroscopy and MD simulations show that the solvated Ni(II) cation is initially coordinated by the oxygens of the [Tf2N](-) anion of IL, which can behave either as mono- or bidentate. Spectroscopic and thermodynamic data show that Ni(II) is able to form up to three stable mononuclear complexes with nitrate in this solvent. The stability constants for Ni(NO3)j complexes (j = 1-3) calculated from spectrophotometry and ITC experiments decrease in the order log K1 > log K2 > log K3. The formation of the first two species is enthalpy-driven, while the third species is entropy-stabilized. The UV-vis spectra of solutions containing different nitrate/Ni(II) ratios show that the metal ion retains the six coordinate geometry. Furthermore, the EXAFS evidences that nitrate is always bidentate. Molecular dynamics simulations show that the [Tf2N](-) anions bind Ni(II) through the sulfonyl oxygen atoms and can coordinate either as monodentate or chelate. The analysis of the MD data shows that introduction of nitrates in the first coordination sphere of the metal ion results in remarkable structural rearrangement of the ionic liquid. PMID- 26999458 TI - Learning From Caregivers About the End of Life in Patients With a Left Ventricular Assist Device. PMID- 26999459 TI - Executive function deficits in team sport athletes with a history of concussion revealed by a visual-auditory dual task paradigm. AB - The purpose of this study was to examine executive functions in team sport athletes with and without a history of concussion. Executive functions comprise many cognitive processes including, working memory, attention and multi-tasking. Past research has shown that concussions cause difficulties in vestibular-visual and vestibular-auditory dual-tasking, however, visual-auditory tasks have been examined rarely. Twenty-nine intercollegiate varsity ice hockey athletes (age = 19.13, SD = 1.56; 15 females) performed an experimental dual-task paradigm that required simultaneously processing visual and auditory information. A brief interview, event description and self-report questionnaires were used to assign participants to each group (concussion, no-concussion). Eighteen athletes had a history of concussion and 11 had no concussion history. The two tests involved visuospatial working memory (i.e., Corsi block test) and auditory tone discrimination. Participants completed both tasks individually, then simultaneously. Two outcome variables were measured, Corsi block memory span and auditory tone discrimination accuracy. No differences were shown when each task was performed alone; however, athletes with a history of concussion had a significantly worse performance on the tone discrimination task in the dual-task condition. In conclusion, long-term deficits in executive functions were associated with a prior history of concussion when cognitive resources were stressed. Evaluations of executive functions and divided attention appear to be helpful in discriminating participants with and without a history concussion. PMID- 26999460 TI - The patient's CMV serological status affects clinical outcome after T-cell replete haplo-HSCT and post-transplant cyclophosphamide. PMID- 26999461 TI - Recovery of physical function and quality of life in patients undergoing hematopoietic stem cell transplantation: a 1-year follow-up. PMID- 26999462 TI - Insufficient immune reconstitution after allogeneic cord blood transplantation without chemotherapy conditioning in patients with SCID caused by CD3delta deficiency. PMID- 26999463 TI - The need for 'onco-nephrology' is increasing in hematopoietic stem cell transplantation. PMID- 26999464 TI - Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation. AB - Relapse remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). The impact of donor type on post relapse survival (PRS) has not been widely examined. We compared the survival outcomes for patients relapsing after haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide with those relapsing after matched-related donor transplantation (MRDT) or matched-unrelated donor transplantation (MUDT) at our institution. Two hundred and thirty-seven consecutive HCT recipients with relapse occurring after HIDT (N=48), MUDT (N=87) and MRDT (N=102) were included in this analysis. Median age was 49 years (19-77 years) and the median time to relapse was 156 days (12-2465) after HCT. HIDT recipients had similar median time to relapse (5.8 vs 4.8 vs 5.5 months, P=0.638) compared with MUDT and MRDT, respectively. One-year PRS was worse among HIDT recipients compared with MRDT and MUDT (17% vs 46% vs 40%, P<0.05). In a multivariate analysis, time to relapse (<3 vs >3 months post transplant), no use of donor lymphocyte infusion (DLI) following relapse, higher Dana Farber disease risk index and HCT comorbidity index scores at the time of transplant and delayed platelet engraftment post transplant were all predictive of worse PRS. This analysis shows that 1-year PRS is inferior among HIDT when compared with MRDT or MUDT. Lower use of DLI after HIDT may have contributed to this inferior survival. PMID- 26999465 TI - Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors. AB - Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, 4 (22%) developed hypothyroidism, 7 (39%) had insulin resistance and 5 (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism and gonadal dysfunction after busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes. PMID- 26999466 TI - Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation. AB - Intestinal dysbiosis has been associated with acute gastrointestinal GvHD and poor outcome following allogeneic stem cell transplantation (ASCT). To assess the effect of a switch in 2012 from ciprofloxacin/metronidazole to rifaximin for gut decontamination on intestinal microbiota composition and ASCT outcome, we retrospectively analyzed 394 patients receiving ASCT from September 2008 through June 2015. In 131 and 90 patients, respectively, urinary 3-indoxyl sulfate levels and intestinal enterococcal load were measured before conditioning and weekly within the first 28 days after ASCT. The use of rifaximin correlated with lower enterococcal positivity (6.9 vs 21.9%, P=0.05) and higher urinary 3-indoxyl sulfate concentrations (10.5 vs 4.6 MUmoL/mmoL crea, P<0.001) after ASCT. Patients on rifaximin showed lower 1-year transplant-related mortality (P=0.04) and higher overall survival (P=0.008). Treatment of infectious complications with systemic antibiotics did not abrogate the beneficial effects of rifaximin on intestinal microbiota composition in the early course of ASCT and outcome. The data underscore the importance of maintaining a diverse population of symbiotic and mutualistic bacteria in the gut on ASCT outcome. PMID- 26999467 TI - Personalized home-based interval exercise training may improve cardiorespiratory fitness in cancer patients preparing to undergo hematopoietic cell transplantation. AB - Impaired cardiorespiratory fitness is associated with inferior survival in patients preparing to undergo hematopoietic cell transplantation (HCT). Exercise training based on short, higher intensity intervals has the potential to efficiently improve cardiorespiratory fitness. We studied home-based interval exercise training (IET) in 40 patients before autologous (N=20) or allogeneic (N=20) HCT. Each session consisted of five, 3 min intervals of walking, jogging or cycling at 65-95% maximal heart rate (MHR) with 3 min of low-intensity exercise (<65% MHR) between intervals. Participants were asked to perform sessions at least three times weekly. The duration of the intervention was at least 6 weeks, depending on each patient's scheduled transplantation date. Cardiorespiratory fitness was assessed from a peak oxygen consumption test (VO2peak) and a 6 min walk (6MWD) before and after the intervention period. For the autologous HCT cohort, improvements in VO2peak (P=0.12) and 6MWD (P=0.19) were not statistically significant. For the allogeneic cohort, the median VO2peak improvement was 3.7 ml/kg min (P=0.005) and the median 6MWD improvement was 34 m (P=0.006). Home-based IET can be performed before HCT and has the potential to improve cardiorespiratory fitness. PMID- 26999468 TI - Haematopoietic cell transplants in Latin America. AB - Haematopoietic cell transplants are done by more than 1500 transplant centres in 75 countries, mostly for life-threatening haematological disorders. However, transplant technology and access are not uniformly distributed worldwide. Most transplants are done predominately in Europe, North America and some Asian countries. We review transplant activity in Latin America, a geographic region with a population of >600 million persons living in countries with diverse economic and social development levels. These data indicate a 20-40-fold lower frequency of transplants in Latin America compared with Europe and North America. We show that although economics, infrastructure and expertise are important limitations, other variables also operate. Changes in several of these variables may substantially increase transplant activity in Latin America. PMID- 26999470 TI - Acute and chronic effects on central hemodynamics and arterial stiffness in professional rowers. AB - Controversial data exist on acute and chronic effects of competitive sports on central hemodynamics and arterial stiffness. We investigated chronic as well as acute training effects in professional rowers. The trial was planned as a non randomized, controlled pilot-study comparing athletes and controls. 13 German national team rowers (24.1 +/- 1.5 years) and 12 controls (23.8 +/- 0.8 years) participated. Aortic, brachial hemodynamics and arterial stiffness were measured (Arteriograph, TensioMed((r)), Hungary) before and after a standardized exercise test. Chronic heart rate (49 [Formula: see text] 2 bpm versus 70 [Formula: see text] 2 bpm, p < 0.05) as well as brachial diastolic pressure (65 [Formula: see text] 2 mmHg versus 74 [Formula: see text] 2 mmHg, p < 0.05) was significantly lower in rowers. Physical power (305 [Formula: see text] 63 versus 158 [Formula: see text] 60 W, p < 0.001) was better. Chronic aortic pulse pressure (41.6 [Formula: see text] 6.0 versus 35.2 [Formula: see text] 3.8 mmHg; p < 0.01) and AIx (9.1 [Formula: see text] 5.4 versus 7.0 [Formula: see text] 10.2; p < 0.01) were significantly higher in athletes. After the all-out test (acute effects) pulse wave velocity (rowers: 6.6 [Formula: see text] 1.2 m s(-1) versus 7.8 [Formula: see text] 1.6 m s(-1), p < 0.001; control group 6.0 [Formula: see text] 0.4 m s(-1) versus 8.0 [Formula: see text] 1.4 m s(-1), p = 0.005) and heart rate (rowers: 49 [Formula: see text] 2 bpm versus 91 [Formula: see text] 3 bpm, p < 0.001; control group 70 [Formula: see text] 2 bpm versus 92 [Formula: see text] 4 bpm, p < 0.001) increased significantly in both groups. The controls' aortic AIx (7.0 [Formula: see text] 10.2 versus 2.0 [Formula: see text] 6.0; p < 0.01) decreased significantly after exercise. Professional rowers showed higher chronic aortic pulse pressure and arterial stiffness. Given the risk associated with elevated aortic pulse pressure and AIx for development of cardiovascular diseases, longterm observations of professional rowers are needed with respect to arterial stiffness and prognosis. Furthermore the acute effects need additional research. PMID- 26999469 TI - Does quality of life impact the decision to pursue stem cell transplantation for elderly patients with advanced MDS? AB - The factors that influence utilization of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HCT) among medically fit older patients with advanced myelodysplastic syndromes (MDS) are largely unknown. The MDS Transplant-Associated Outcomes (MDS-TAO) study is an ongoing prospective observational study at the Dana-Farber Cancer Institute and Massachusetts General Hospital that enrolls transplant-eligible fit patients aged 60-75 years with advanced MDS and follows them through RIC HCT vs non-HCT treatment. In this analysis of 127 patients enrolled from May 2011 to June 2014, we examined the influence of age, gender, cytogenetics, International Prognostic Scoring System (IPSS) category, performance status, distance from HCT center and baseline patient-reported quality of life (QOL) from the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) on the likelihood of receiving RIC HCT using competing risk regression modeling. With a median follow-up of 16 months, 44 patients (35%) had undergone RIC HCT. In multivariable analyses, age (hazard ratio (HR) 0.87 per year, 95% confidence interval (CI): 0.81-0.92, P<0.001) and higher IPSS (intermediate-2/high; HR 2.29, 95% CI: 1.25-4.19, P=0.007) were significantly predictive of receipt of RIC HCT; neither global QOL score nor any QOL subscales scores were predictive. These data suggest that baseline patient-reported QOL has little influence on the decision to undergo RIC HCT for older patients with advanced MDS. PMID- 26999471 TI - A Contemporary Framework and Suprastructure Ceramic Design for Posterior Implant Fixed Partial Denture. AB - Bone and soft tissue deformities in long-standing partial edentulism are commonly treated with implant therapy. The various ceramic restorative systems available and digital technology allow for customization of design and material selection. A substructure design that mimics tooth preparation in a custom zirconia framework with a lithium disilicate suprastructure is presented as an effort to address the functional and esthetic challenges posed by long-standing posterior partial edentulism. The aim is to present several contemporary elements of design to address the functional, esthetic, and maintenance needs. PMID- 26999472 TI - Trends in brain-dead organ donor characteristics: a 13-year analysis. AB - BACKGROUND: Driven by disease trends, such as obesity and metabolic syndrome, that are increasingly prevalent in the general population, we aimed to evaluate the comorbidities and attributes of the brain-dead organ donor population over time in a longitudinal study. METHODS: We compared overall health and baseline attributes of organ donors between 2000-2005 and 2006-2012 using our prospective transplant database. Descriptive and comparative analyses of the 2 historical cohorts were performed. RESULTS: A total of 1040 brain-dead organ donors were included in our analysis: 496 from the 2000-2005 period and 544 from the 2006 2012 period. Our analysis revealed that donors from the recent (2006-2012) period were more likely to have increased body mass index (26.4 +/- 6.0 v. 25.0 +/- 4.8, p = 0.003), smoking history (57.0% v. 27.2%, p < 0.001), coronary artery disease (14.3% v. 3.2%, p = 0.015) and dyslipidemia (19.1% v. 4.2%, p < 0.001), but less likely to have concurrent infection (1.1% v. 7.9%, p < 0.001) than those from the earlier period. CONCLUSION: Our data suggest that the characteristics and comorbidities of brain-dead organ donors have somewhat deteriorated over the last decade. Further studies are needed to evaluate the impact of these health attributes on donated organ utilization and outcomes. PMID- 26999473 TI - Creation of the sole regional laser lead extraction program serving Atlantic Canada: initial experience. AB - BACKGROUND: An increasing need for laser lead extraction has grown in parallel with the increase of implantation of pacing and defibrillating devices. We reviewed the initial experience of a regional laser-assisted lead extraction program serving Atlantic Canada. METHODS: We retrospectively reviewed the cases of all consecutive patients who underwent laser lead extraction at the Maritime Heart Centre in Halifax, NS, between 2006 and 2015. We conducted univariate and Kaplan-Meier survivorship analyses. RESULTS: During the 9-year study period, 108 consecutive patients underwent laser lead extractions (218 leads extracted). The most common indication for extraction was infection (84.3%). Most patients were older than 60 years (73.1%) and had leads chronically implanted; the explanted leads were an average of 7.5 +/- 6.8 years old. Procedural and clinical success (resolution of preoperative symptoms) rates and mortality were 96.8%, 97.2%, and 0.9%, respectively. Sternotomy procedures were performed in 3 instances: once for vascular repair due to perforation and twice to ensure that all infected lead material was removed. No minor complications required surgical intervention. Survival after discharge was 98.4% at 30 days and 94% at 12 months. CONCLUSION: Atlantic Canada's sole surgical extraction centre achieved high extraction success with a low complication rate. Lead extraction in an operative setting provides for immediate surgical intervention and is essential for the survival of patients with complicated cases. Surgeons must weigh the risks versus benefits in patients older than 60 years who have chronically implanted leads (> 1 yr) and infection. PMID- 26999474 TI - Understanding the complexities of shared decision-making in cancer: a qualitative study of the perspectives of patients undergoing colorectal surgery. AB - BACKGROUND: Decisions leading up to surgery are fraught with uncertainty owing to trade-offs between treatment effectiveness and quality of life. Past studies on shared decision-making (SDM) have focused on the physician-patient encounter, with little emphasis on familial and cultural factors. The literature is scarce in surgical oncology, with few studies using qualitative interviews. Our objective was to explore the complexities of SDM within the setting of colorectal cancer (CRC) surgery. METHODS: An interdisciplinary team developed a semistructured questionnaire. Telephone interviews were conducted with CRC patients in the practice of 1 surgical oncologist. Data saturation was achieved and a descriptive thematic analysis was performed. RESULTS: We interviewed 20 patients before achieving data saturation. Three major themes emerged. First, family was considered as a crucial adjunct to the patient-provider dyad. Second, patients identified several facilitators to SDM, including a robust social support system and a competent surgical team. Although language was a perceived barrier, there was no difference in level of involvement in care between patients who spoke English fluently and those who did not. Finally, patients perceived a lack of choice and control in decision-making, thus challenging the very notion of SDM. CONCLUSION: Surgeons must learn to appreciate the role of family as a vital addition to the patient-provider dyad. Family engagement is crucial for CRC patients, particularly those undergoing surgical resection of late-stage disease. Surgeons must be aware of the uniqueness of decision-making in this context to empower patients and families. PMID- 26999475 TI - Making the transition from video-assisted thoracoscopic surgery to chest tube with fibrinolytics for empyema in children: Any change in outcomes? AB - BACKGROUND: There is ongoing variation in the use of video-assisted thoracoscopic surgery (VATS) and chest tube with fibrinolytics (CTWF) for empyema in children. Our objective was to report outcomes from a centre that recently made the transition from VATS to CTWF as the primary treatment modality. METHODS: We conducted a historical cohort study of children with empyema treated with either primary VATS (between 2005 and 2009) or CTWF (between 2009 and 2013). RESULTS: Sixty-seven children underwent pleural drainage for empyema during the study period: 28 (42%) were treated with primary VATS, and 39 (58%) underwent CTWF. There were no significant differences between the VATS and CTWF groups for length of stay (8 v. 9 d, p = 0.61) or need for additional procedures (4% v. 13%, p = 0.19). Length of stay varied widely for both VATS (4-53 d) and CTWF (5-46 d). Primary VATS failed in 1 (4%) patient, who required an additional chest tube, and CTWF failed in 5 (13%) patients. Additional procedures included 3 rescue VATS, 2 additional chest tubes and 1 thoracotomy. All patients recovered and were discharged home. CONCLUSION: Primary VATS and CTWF were associated with similar outcomes in children with empyema. There appears to be a subset of children at risk for treatment failure with CTWF. Further research is needed to determine if these patients would benefit from primary VATS. PMID- 26999476 TI - The impact of adverse events on health care costs for older adults undergoing nonelective abdominal surgery. AB - BACKGROUND: Postoperative complications have been identified as an important and potentially preventable cause of increased hospital costs. While older adults are at increased risk of experiencing complications and other adverse events, very little research has specifically examined how these events impact inpatient costs. We sought to examine the association between postoperative complications, hospital mortality and loss of independence and direct inpatient health care costs in patients 70 years or older who underwent nonelective abdominal surgery. METHODS: We prospectively enrolled consecutive patients 70 years or older who underwent nonelective abdominal surgery between July 1, 2011, and Sept. 30, 2012. Detailed patient-level data were collected regarding demographics, diagnosis, treatment and outcomes. Patient-level resource tracking was used to calculate direct hospital costs (2012 $CDN). We examined the association between complications, hospital mortality and loss of independence cost using multiple linear regression. RESULTS: During the study period 212 patients underwent surgery. Overall, 51.9% of patients experienced a nonfatal complication (32.5% minor and 19.4% major), 6.6% died in hospital and 22.6% experienced a loss of independence. On multivariate analysis nonfatal complications (p < 0.001), hospital mortality (p = 0.021) and loss of independence at discharge (p < 0.001) were independently associated with health care costs. These adverse events respectively accounted for 30%, 4% and 10% of the total costs of hospital care. CONCLUSION: Adverse events were common after abdominal surgery in older adults and accounted for 44% of overall costs. This represents a substantial opportunity for better patient outcomes and cost savings with quality improvement strategies tailored to the needs of this high-risk surgical population. PMID- 26999477 TI - Two years changes in the development of caudate nucleus are involved in restricted repetitive behaviors in 2-5-year-old children with autism spectrum disorder. AB - Caudate nucleus volume is enlarged in autism spectrum disorder (ASD) and is associated with restricted and repetitive behaviors (RRBs). However, the trajectory of caudate nucleus volume in RRBs of young children remains unclear. Caudate nucleus volume was measured in 36 children with ASD and 18 matched 2-3 year-old subjects with developmentally delayed (DD) at baseline (Time 1) and at 2 year follow-up (Time 2). The differential growth rate in caudate nucleus volume was calculated. Further, the relationships between the development of caudate nucleus volume and RRBs were analyzed. Our results showed that caudate nucleus volume was significantly larger in the ASD group at both time points and the magnitude of enlargement was greater at Time 2. The rate of caudate nucleus growth during this 2-year interval was faster in children with ASD than DD. Right caudate nucleus volume growth was negatively correlated with RRBs. Findings from this study suggest developmental abnormalities of caudate nucleus volume in ASD. Longitudinal MRI studies are needed to explore the correlation between atypical growth patterns of caudate nucleus and phenotype of RRBs. PMID- 26999479 TI - Layered reduced graphene oxide with nanoscale interlayer gaps as a stable host for lithium metal anodes. AB - Metallic lithium is a promising anode candidate for future high-energy-density lithium batteries. It is a light-weight material, and has the highest theoretical capacity (3,860 mAh g(-1)) and the lowest electrochemical potential of all candidates. There are, however, at least three major hurdles before lithium metal anodes can become a viable technology: uneven and dendritic lithium deposition, unstable solid electrolyte interphase and almost infinite relative dimension change during cycling. Previous research has tackled the first two issues, but the last is still mostly unsolved. Here we report a composite lithium metal anode that exhibits low dimension variation (~20%) during cycling and good mechanical flexibility. The anode is composed of 7 wt% 'lithiophilic' layered reduced graphene oxide with nanoscale gaps that can host metallic lithium. The anode retains up to ~3,390 mAh g(-1) of capacity, exhibits low overpotential (~80 mV at 3 mA cm(-2)) and a flat voltage profile in a carbonate electrolyte. A full-cell battery with a LiCoO2 cathode shows good rate capability and flat voltage profiles. PMID- 26999478 TI - Cobimetinib and vemurafenib for the treatment of melanoma. AB - INTRODUCTION: Cobimetinib combined with vemurafenib is a new approved MEK inhibitor for first line treatment of metastatic melanoma patients with BRAF V600 mutations. It improves tumor response rates and progression free survival compared to vemurafenib alone, while decreasing toxicities due to the paradoxical activation of the MAPK signaling pathway. AREAS COVERED: This review covers the pharmacology, efficacy, and toxicity data derived from clinical and preclinical studies on cobimetinib. It also reports ongoing trials evaluating cobimetinib to better understand future developments for this drug. EXPERT OPINION: The combination of cobimetinib and vemurafenib seems to be more toxic than the combination therapy dabrafenib and trametinib even if these four drugs have never been compared in a randomized trial. The future of this combination depends on its capacity to be combined simultaneously or sequentially with immune based therapies to improve the durability of responses. PMID- 26999480 TI - Diagnostic devices: Managing diabetes through the skin. PMID- 26999481 TI - A spin-orbit torque switching scheme with collinear magnetic easy axis and current configuration. AB - Spin-orbit torque, a torque brought about by in-plane current via the spin-orbit interactions in heavy-metal/ferromagnet nanostructures, provides a new pathway to switch the magnetization direction. Although there are many recent studies, they all build on one of two structures that have the easy axis of a nanomagnet lying orthogonal to the current, that is, along the z or y axes. Here, we present a new structure with the third geometry, that is, with the easy axis collinear with the current (along the x axis). We fabricate a three-terminal device with a Ta/CoFeB/MgO-based stack and demonstrate the switching operation driven by the spin-orbit torque due to Ta with a negative spin Hall angle. Comparisons with different geometries highlight the previously unknown mechanisms of spin-orbit torque switching. Our work offers a new avenue for exploring the physics of spin orbit torque switching and its application to spintronics devices. PMID- 26999483 TI - Safety and outcomes of decompressive craniectomy after intravenous tissue plasminogen activator administration for malignant cerebral infarction. AB - OBJECTIVE: The aim of this study was to evaluate the safety and outcomes of decompressive craniectomy (DC) after intravenous tissue plasminogen activator (IV tPA) administration for malignant cerebral infarction. METHODS: We retrospectively reviewed patients who underwent DC for malignant cerebral infarction. We compared fourteen patients who underwent DC after IV tPA administration with another nine patients who underwent DC without prior IV tPA administration. RESULTS: Twenty-three patients underwent DC for malignant hemispheric cerebral infarction in our hospital for five years. Fibrinolysis was performed prior to the DC in fourteen patients (60,9%). The patients characteristics did not differ between the DC patients with and without prior IV tPA administration. The complications that developed after DC were similar in both groups: in patients who underwent DC after IV tPA administration, 9 (64.3%) developed haemorrhagic transformation and 6 (42.9%) developed hydrocephalus. The functional outcome, as the 6-month GOS, was similar in both groups (p = 0.762). ICU mortality (p = 0.329) and hospital mortality after ICU (p= 0.634) were also similar between the two groups. CONCLUSION: Although the main limitation is that the number of patients in our serie was small, which reduced the statistical power, our study suggest that DC after failure of IV tPA administration for malignant cerebral infarction is safe and did not cause an excess of complications arising from the use of fibrinolytic. PMID- 26999482 TI - A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. AB - Owing to its high carrier mobility, conductivity, flexibility and optical transparency, graphene is a versatile material in micro- and macroelectronics. However, the low density of electrochemically active defects in graphene synthesized by chemical vapour deposition limits its application in biosensing. Here, we show that graphene doped with gold and combined with a gold mesh has improved electrochemical activity over bare graphene, sufficient to form a wearable patch for sweat-based diabetes monitoring and feedback therapy. The stretchable device features a serpentine bilayer of gold mesh and gold-doped graphene that forms an efficient electrochemical interface for the stable transfer of electrical signals. The patch consists of a heater, temperature, humidity, glucose and pH sensors and polymeric microneedles that can be thermally activated to deliver drugs transcutaneously. We show that the patch can be thermally actuated to deliver Metformin and reduce blood glucose levels in diabetic mice. PMID- 26999484 TI - Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies for Acute Coronary Syndrome: A Narrative Review. AB - Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) are an emerging therapy for dyslipidemia. Acute coronary events induce a dynamic increase of PCSK9 levels that may play a role in plaque vulnerability of both culprit and nonculprit coronary vessels. Growing evidence highlights a potential key role of PCSK9 antibodies in managing acute coronary syndrome. This review describes the influence of PCSK9 antibodies on plaque composition and instability, as well as the pharmacokinetic profile and the potential anti inflammatory and antithrombotic mechanisms associated with PCSK9 inhibition that may confer benefits during the early phase of acute coronary syndrome. The authors posit a rationale for the use of PCSK9 antibodies in patients with acute coronary syndrome and highlight the need for further investigation in this area. PMID- 26999486 TI - Editorial. PMID- 26999489 TI - Metabolic syndrome and hypogonadism--two peas in a pod. AB - Testosterone deficiency is highly prevalent in up to 50% of men with the metabolic syndrome and type 2 diabetes mellitus. Low testosterone levels in men appear to be an independent cardiovascular risk factor and predictor of subsequent development of the metabolic syndrome. Reciprocally, the metabolic syndrome leads to a decrease in testosterone levels. This review provides an account of the pathophysiological mechanisms in the bidirectional relationship between hypogonadism and body composition, inflammation and insulin sensitivity as well as the effects of testosterone replacement on diverse metabolic parameters. PMID- 26999488 TI - Use of Quantitative Dynamic Contrast-Enhanced Ultrasound to Assess Response to Antiangiogenic Therapy in Children and Adolescents With Solid Malignancies: A Pilot Study. AB - OBJECTIVE: The purpose of this study was to investigate contrast-enhanced ultrasound assessment of tumor response to antiangiogenic therapy in children and adolescents with solid malignancies. SUBJECTS AND METHODS: Children with recurrent solid tumors who were enrolled in an institutional phase 1 study of antiangiogenic therapy underwent contrast-enhanced ultrasound of target lesions before therapy, on therapy days 3 and 7, and at the end of course 1. Acoustic data from target lesion ROIs were used to measure peak enhancement, time to peak, rate of enhancement, total AUC, AUC during wash-in (AUC1), and AUC during washout (AUC2). The Cox regression model was used to assess the association between changes in parameters from baseline to follow-up time points and time to tumor progression. Values of p <= 0.050 were considered significant. RESULTS: Target lesion sites included liver (n = 3), pleura (n = 2), and supraclavicular mass, soft-tissue component of bone metastasis, lung, retroperitoneum, peritoneum, lymph node, muscle mass, and perineum (n = 1 each). Hazard ratios for changes from baseline to end of course 1 for peak enhancement (1.17, p = 0.034), rate of enhancement (3.25, p = 0.029), and AUC1 (1.02, p = 0.040) were significantly associated with time to progression. Greater decreases in these parameters correlated with longer time to progression. CONCLUSION: Contrast-enhanced ultrasound measurements of tumor peak enhancement, rate of enhancement, and AUC1 were early predictors of time to progression in a cohort of children and adolescents with recurrent solid tumors treated with antiangiogenic therapy. Further investigation of these findings in a larger population is warranted. PMID- 26999490 TI - Recent developments in second and third line therapy of metastatic renal cell carcinoma. PMID- 26999491 TI - Synthesis of "amphiphilic" carbon dots and their application for the analysis of iodine species (I2, I(-) and IO3(-)) in highly saline water. AB - "Amphiphilic" carbon dots (A-CDs) with a strong green fluorescence emission were synthesized by a simple and green method at room temperature. The characterization demonstrated that the synthesized A-CDs have both hydrophilic and hydrophobic properties and could be dispersed well in aqueous and organic solutions. As a fluorescent probe, the fluorescence of A-CDs could be obviously quenched in the presence of iodine (I2) and the quenching rate is proportional to the concentration of I2. Therefore, the A-CDs could be used as fluorophores for the detection of I2 with higher selectivity and sensitivity, and the linear working range for the I2 sensor is 80 nM-10 MUM with a detection limit of 3.5 nM (S/N = 3). More interesting is that IO3(-) and I(-) could be transformed to I2 with different sample treatment processes, therefore, the I2 sensor based on A CDs could also be used for the analysis of iodine species (I2, I(-) and IO3(-)) in samples. The possible mechanism has also been discussed in this work, and the high selectivity response to I2 can be attributed to the amphiphilic properties of A-CDs, which bring I2 closer to A-CDs and quench their fluorescence. The proposed I2 sensor has been successfully used for the analysis of iodine species in highly saline water, and the satisfactory results of detection and analysis of iodine species in samples demonstrate that the developed I2 sensor based on A-CDs has potential application in the fields of environment and clinical medicine. PMID- 26999485 TI - Psychiatric Diagnoses and Comorbidities in a Diverse, Multicity Cohort of Young Transgender Women: Baseline Findings From Project LifeSkills. AB - IMPORTANCE: Transgender youth, including adolescent and young adult transgender women assigned a male sex at birth who identify as girls, women, transgender women, transfemale, male-to-female, or another diverse transfeminine gender identity, represent a vulnerable population at risk for negative mental health and substance use outcomes. Diagnostic clinical interviews to assess prevalence of mental health, substance dependence, and comorbid psychiatric disorders in young transgender women remain scarce. OBJECTIVE: To report the prevalence of mental health, substance dependence, and comorbid psychiatric disorders assessed via clinical diagnostic interview in a high-risk community-recruited sample of young transgender women. DESIGN, SETTING, AND PARTICIPANTS: Observational study reporting baseline finding from a diverse sample of 298 sexually active, young transgender women aged 16 through 29 years (mean age, 23.4 years; 49.0% black, 12.4% Latina, 25.5% white, and 13.1% other minority race/ethnicity) and enrolled in Project LifeSkills, an ongoing randomized controlled HIV prevention intervention efficacy trial in Chicago and Boston, between 2012 and 2015. EXPOSURE: Transfeminine gender identity. MAIN OUTCOMES AND MEASURES: Age- and site-adjusted prevalence and comorbidities of mental health and substance dependence disorders assessed via the Mini-International Neuropsychiatric Interview, including 1 or more diagnoses, 2 or more comorbid diagnoses, major depressive episode (current and lifetime), past 30-day suicidal risk (no/low risk vs moderate/high risk), past 6-month generalized anxiety disorder and posttraumatic stress disorder, and past 12-month alcohol dependence and nonalcohol psychoactive substance use dependence. RESULTS: Of the 298 transgender women, 41.5% of participants had 1 or more mental health or substance dependence diagnoses; 1 in 5 (20.1%) had 2 or more comorbid psychiatric diagnoses. Prevalence of specific disorders was as follows: lifetime and current major depressive episode, 35.4% and 14.7%, respectively; suicidality, 20.2%; generalized anxiety disorder, 7.9%; posttraumatic stress disorder, 9.8%; alcohol dependence, 11.2%; and nonalcohol psychoactive substance use dependence, 15.2%. CONCLUSIONS AND RELEVANCE: Prevalence of psychiatric diagnoses was high in this community-recruited sample of young transgender women. Improving access to routine primary care, diagnostic screening, psychotherapy, and pharmacologic treatments, and retention in care in clinical community-based, pediatric, and adolescent medicine settings are urgently needed to address mental health and substance dependence disorders in this population. Further research will be critical, particularly longitudinal studies across development, to understand risk factors and identify optimal timing and targets for psychosocial interventions. PMID- 26999492 TI - Hydrological processes at Inle Lake (Southern Shan State, Myanmar) inferred from hydrochemical, mineralogical and isotopic data. AB - A one-year hydrochemical and isotopic monitoring was conducted at the Inle Lake, the second largest lake in Myanmar, also considering sediment samples. Lake waters are characterised by low electrical conductivities (236-489 MUS/cm), neutral to alkaline pH (7.36-9.26), oxidising Eh (329-457 mV) and Ca-Mg-HCO3 facies. Stable isotopes indicate that lake waters are only slightly affected by evaporation, are fully flushed yearly and are not stratified. Carbonate equilibria dominate the lake water hydrochemistry. In summer, photosynthetic activity and temperature increase induce calcite precipitation, as testified by its high content in the sediments, up to 97 %, and by its isotopic composition. The short residence time and endogenic calcite precipitation likely prevent the accumulation of contaminants and nutrients in lake waters. This study suggests a high resilience of the system to anthropogenic disturbances and demonstrates the sediment potential for the reconstruction of the environmental evolution in time and for the anthropogenic impact assessment. PMID- 26999493 TI - The emergence of point-of-care blood-based biomarker testing for psychiatric disorders: enabling personalized medicine. AB - For psychiatric disorders, repeated failures in converting scientific discoveries into novel drugs has precipitated a crisis and eroded confidence in drug discovery. This review describes how current and future innovations driven by application of biomarkers can help to re-initiate research in this area. This will have positive impact on the field of psychiatry and result in application of sensitive and specific biochemical tests in parallel with the traditional questionnaires for improved diagnosis. Furthermore, application of emerging biosensor tools will facilitate point-of-care testing by fusion of biochemical and clinical data. In this way, patient data will be comprised of past medical histories, biopatterns and prognosis information, resulting in personalized profiles or molecular fingerprints for patients with these conditions. PMID- 26999494 TI - Myeloma of the central nervous system - an ongoing conundrum! PMID- 26999495 TI - Controlled assembly of heterotypic cells in a core-shell scaffold: organ in a droplet. AB - This paper reports a droplet-based microfluidic approach to fabricate a large number of monodisperse, portable microtissues, each in an individual drop. We use water-water-oil double emulsions as templates and spatially assemble hepatocytes in the core and fibroblasts in the shell, forming a 3D liver model in a drop. PMID- 26999496 TI - Vibronic Dynamics of the Ultrafast all-trans to 13-cis Photoisomerization of Retinal in Channelrhodopsin-1. AB - Channelrhodopsins are light-gated ion channels with extensive applications in optogenetics. Channelrhodopsin-1 from Chlamydomonas augustae (CaChR1) exhibits a red-shifted absorption spectrum as compared to Channelrhodopsin-2, which is highly beneficial for optogenetic application. The primary event in the photocycle of CaChR1 involves an isomerization of the protein-bound retinal chromophore. Here, we apply highly time-resolved vibronic spectroscopy to reveal the electronic and structural dynamics associated with the first step of the photocycle of CaChR1. We observe vibrationally coherent formation of the P1 intermediate exhibiting a twisted 13-cis retinal with a 110 +/- 7 fs time constant. Comparison with low-temperature resonance Raman spectroscopy of the corresponding trapped photoproduct demonstrates that this rapidly formed P1 intermediate is stable for several hundreds of nanoseconds. PMID- 26999497 TI - Outcome of acute intestinal failure. AB - BACKGROUND: Type 2 acute intestinal failure is characterized by the need for parenteral nutrition (PN) for several months, and is typically caused by complications of abdominal surgery with enteric fistulas or proximal stomas. This study aimed to evaluate clinical management according to quality indicators established by the Association of Surgeons of Great Britain and Ireland. METHODS: Consecutive patients with type 2 intestinal failure referred to a specialized centre were analysed. Outcomes included the rate of discontinuation of PN, morbidity and mortality. RESULTS: Eighty-nine patients were analysed, of whom 57 had an enteric fistula, 29 a proximal stoma (6 with distal fistulas), and three had intestinal failure owing to other causes. One patient was deemed inoperable, and nine patients died from underlying illness during initial management. Before reconstructive surgery, 94 per cent (65 of 66 operated and 3 patients scheduled for surgery) spent the period of rehabilitation at home. Discontinuation of PN owing to restoration of enteral autonomy was achieved in 65 (73 per cent) of 89 patients. Seven patients developed a recurrent fistula, which was successfully managed with a further operation in four, resulting in successful fistula takedown in 41 of 44 patients undergoing fistula resection. Three patients (5 per cent) died in hospital after reconstructive surgery. The overall mortality rate in this series, including preoperative deaths from underlying diseases, was 16 per cent (14 patients). CONCLUSION: Intestinal failure care and reconstructive surgery resulted in successful discontinuation of PN in the majority of patients, although disease-related mortality was considerable. PMID- 26999498 TI - From function to structure take the archaeal TRAM. PMID- 26999499 TI - Ru Nanoframes with an fcc Structure and Enhanced Catalytic Properties. AB - Noble-metal nanoframes are of great interest to many applications due to their unique open structures. Among various noble metals, Ru has never been made into nanoframes. In this study, we report for the first time an effective method based on seeded growth and chemical etching for the facile synthesis of Ru nanoframes with high purity. The essence of this approach is to induce the preferential growth of Ru on the corners and edges of Pd truncated octahedra as the seeds by kinetic control. The resultant Pd-Ru core-frame octahedra could be easily converted to Ru octahedral nanoframes of ~2 nm in thickness by selectively removing the Pd cores through chemical etching. Most importantly, in this approach the face-centered cubic (fcc) crystal structure of Pd seeds was faithfully replicated by Ru that usually takes an hcp structure. The fcc Ru nanoframes showed higher catalytic activities toward the reduction of p nitrophenol by NaBH4 and the dehydrogenation of ammonia borane compared with hcp Ru nanowires with roughly the same thickness. PMID- 26999500 TI - About BRAF Mutations and p16 Expression in Melanomas Associated With Blue Nevi or Mimicking Cellular Blue Nevi. PMID- 26999501 TI - CD1a Reactivity in Non-neoplastic Adenohypophysis. AB - Within the differential diagnosis of patients presenting with sellar or suprasellar lesions is Langerhans cell histiocytosis (LCH). CD1a staining is frequently used to identify the presence of an abnormal proliferation of Langerhans cells on histologic sections and contributes to the diagnosis of LCH. Here, we report that the MTB-1 monoclonal antibody against the CD1a antigen reacts to native adenohypophyseal epithelial cells. We show that immunohistochemistry for CD1a exhibits strong positivity in all autopsy and surgically resected non-neoplastic adenohypophysis tested. Thus, CD1a positivity by itself should be interpreted with caution, and we recommend the routine use of a panel of stains including CD1a, Langerin, and synaptophysin in conjunction with morphologic analysis before a diagnosis of LCH is rendered. In addition, we find that pituitary adenomas fail to stain for CD1a prompting consideration of the utility of this stain as a marker for non-neoplastic gland. PMID- 26999502 TI - NRASQ61R and BRAFV600E Mutation-specific Immunohistochemistry Is a Helpful Tool to Diagnose Metastatic Undifferentiated/Dedifferentiated Melanomas. PMID- 26999503 TI - Biphasic Squamoid Alveolar Renal Cell Carcinoma: A Distinctive Subtype of Papillary Renal Cell Carcinoma? AB - Biphasic squamoid alveolar renal cell carcinoma (BSARCC) has been recently described as a distinct neoplasm. Twenty-one cases from 12 institutions were analyzed using routine histology, immunohistochemistry, array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization. Tumors were removed from 11 male and 10 female patients, whose age ranged from 53 to 79 years. The size of tumors ranged from 1.5 to 16 cm. Follow-up information was available for 14 patients (range, 1 to 96 mo), and metastatic spread was found in 5 cases. All tumors comprised 2 cell populations arranged in organoid structures: small, low grade neoplastic cells with scant cytoplasm usually lining the inside of alveolar structures, and larger squamoid cells with more prominent cytoplasm and larger vesicular nuclei arranged in compact nests. In 9/21 tumors there was a visible transition from such solid and alveolar areas into papillary components. Areas composed of large squamoid cells comprised 10% to 80% of total tumor volume. Emperipolesis was present in all (21/21) tumors. Immunohistochemically, all cases were positive for cytokeratin 7, EMA, vimentin, and cyclin D1. aCGH (confirmed by fluorescence in situ hybridization) in 5 analyzable cases revealed multiple numerical chromosomal changes including gains of chromosomes 7 and 17 in all cases. These changes were further disclosed in 6 additional cases, which were unsuitable for aCGH. We conclude that tumors show a morphologic spectrum ranging from RCC with papillary architecture and large squamoid cells to fully developed BSARCC. Emperipolesis in squamoid cells was a constant finding. All BSARCCs expressed CK7, EMA, vimentin, and cyclin D1. Antibody to cyclin D1 showed a unique and previously not recognized pattern of immunohistochemical staining. Multiple chromosomal aberrations were identified in all analyzable cases including gains of chromosomes 7 and 17, indicating that they are akin to papillary RCC. Some BSARCCs were clinically aggressive, but their prognosis could not be predicted from currently available data. Present microscopic, immunohistochemical, and molecular genetic data strongly support the view that BSARCC is a distinctive and peculiar morphologic variant of papillary RCC. PMID- 26999504 TI - A randomized controlled trial of the web-based OurRelationship program: Effects on relationship and individual functioning. AB - OBJECTIVE: Within the United States, one third of married couples are distressed and almost half of first marriages (and more than half of unmarried cohabiting relationships) end in divorce/separation. Additionally, relationship distress has been linked to mental and physical health problems in partners and their children. Although couple therapy is effective in reducing relationship distress, it is utilized by less than one third of divorcing couples. Therefore, more accessible interventions for relationship distress are needed. METHOD: This study tests the efficacy of the OurRelationship program, an 8-hr online program adapted from an empirically based, in-person couple therapy. In the program, couples complete online activities and have 4 15-min calls with project staff. Nationwide, 300 heterosexual couples (N = 600 participants) participated; couples were generally representative of the US in terms of race, ethnicity, and education. Couples were randomly assigned to begin the program immediately or to a 2-month waitlist control group. RESULTS: Compared to the waitlist group, intervention couples reported significant improvements in relationship satisfaction (Cohen's d = 0.69), relationship confidence (d = 0.47), and negative relationship quality (d = 0.57). Additionally, couples reported significant improvements in multiple domains of individual functioning, especially when individuals began the program with difficulties in that domain: depressive (d = 0.71) and anxious symptoms (d = 0.94), perceived health (d = 0.51), work functioning (d = 0.57), and quality of life (d = 0.44). CONCLUSIONS: In a nationally representative sample of couples, the OurRelationship program was effective in significantly improving both relationship and individual functioning, suggesting it can substantially increase the reach of current interventions through its low-cost, Web-based format. PMID- 26999505 TI - CAREST--Multilingual Regional Integration for Health Promotion and Research on Sickle Cell Disease and Thalassemia. AB - Sickle cell disease (SCD) is a significant problem in the Caribbean, where many individuals have African and Asian forebears. However, reliable prevalence data and specific health care programs for SCD are often missing in this region. Closer collaboration between Caribbean territories initiated in 2006 to set up strategies to promote better equity in the health care system for SCD patients led to the formation of CAREST: the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. We present the effectiveness of collaborations established by CAREST to promote SCD newborn screening programs and early childhood care, to facilitate health worker training and approaches for prevention and treatment of SCD complications, and to carry out inter-Caribbean research studies. PMID- 26999506 TI - Return to play after treatment of shoulder labral tears in professional hockey players. AB - OBJECTIVES: Shoulder labral injuries in professional hockey players are often treated surgically to minimize missed ice time. Previous studies have shown that post-operative outcomes in these players are favorable, although they have not specifically focused on athletic performance and time to return to sport. Our objective was to report time to return to play and post-operative on-ice performance metrics after shoulder labral repair in professional ice hockey players. METHODS: We performed a retrospective review of the clinical records of all professional hockey players (NHL) who underwent arthroscopic shoulder labral repair by one surgeon between January 2004 and December 2008. Operative data included labral injury type, number of anchors used, concomitant pathology, and complications. Player information included position, shooting hand, games played before and after surgery, date of return to play (RTP), time on ice (TOI) and shots on goal before and after surgery. Paired sample t-test and independent sample t-tests or their non-parametric equivalents were used to compare pre-and post-operative player performance variables using the SPSS statistical package. RESULTS: Eleven NHL Players (13 shoulders) were included in the study. The average follow-up was 19.4 months (12.7-37 months, SD 7.4) and average age was 29 years (20-36, SD 5.1). Of the 13 shoulders, there were various types of labral tears including three Bankart tears, three superior (SLAP) tears, two posterior tears, three combined anterior/posterior tears, and two panlabral tears. All 11 players returned to play (RTP) after surgery at an average time of 4.3 months. There were no significant differences between time to RTP for players with dominant-sided injuries (4.2 months) and non-dominant injuries (4.6 months), p = 0.632. Five players had increased time-on-ice (TOI) and five players had decreased TOI after surgery, though this difference was not significant (p = 0.3804). On average, the shots on goal per game played (SOG/GP) decreased by 0.13 after surgery which was not significantly different (p = 0.149). There were no post-operative complications observed. CONCLUSION: Professional ice hockey players can safely return to full competition at an average of 4.3 months after arthroscopic shoulder labral repair without significant decline in player performance. PMID- 26999507 TI - Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody. AB - Despite recent advances in melanoma treatment through the use of anti-PD-1 (aPD1) immunotherapy, the efficacy of this method remains to be improved. Here we report an innovative self-degradable microneedle (MN) patch for the sustained delivery of aPD1 in a physiologically controllable manner. The microneedle is composed of biocompatible hyaluronic acid integrated with pH-sensitive dextran nanoparticles (NPs) that encapsulate aPD1 and glucose oxidase (GOx), which converts blood glucose to gluconic acid. The generation of acidic environment promotes the self dissociation of NPs and subsequently results in the substantial release of aPD1. We find that a single administration of the MN patch induces robust immune responses in a B16F10 mouse melanoma model compared to MN without degradation trigger or intratumoral injection of free aPD1 with the same dose. Moreover, this administration strategy can integrate with other immunomodulators (such as anti CTLA-4) to achieve combination therapy for enhancing antitumor efficacy. PMID- 26999508 TI - Photocatalytic Nanostructuring of Graphene Guided by Block Copolymer Self Assembly. AB - Nanostructured graphene exhibits many intriguing properties. For example, precisely controlled graphene nanomeshes can be applied in electronic, photonic, or sensing devices. However, fabrication of nanopatterned graphene with periodic supperlattice remains a challenge. In this work, periodic graphene nanomesh was fabricated by photocatalysis of single-layer graphene suspended on top of TiO2 covered nanopillars, which were produced by combining block copolymer nanolithography with atomic layer deposition. Graphene nanoribbons were also prepared by the same method applied to a line-forming block copolymer template. This mask-free and nonchemical/nonplasma route offers an exciting platform for nanopatterning of graphene and other UV-transparent materials for device engineering. PMID- 26999509 TI - Discovery of Potent Benzofuran-Derived Diapophytoene Desaturase (CrtN) Inhibitors with Enhanced Oral Bioavailability for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections. AB - Blocking the staphyloxanthin biosynthesis process has emerged as a new promising antivirulence strategy. Previously, we first revealed that CrtN is a druggable target against infections caused by pigmented Staphylococcus aureus (S. aureus) and that naftifine was an effective CrtN inhibitor. Here, we identify a new type of benzofuran-derived CrtN inhibitor with submicromolar IC50 values that is based on the naftifine scaffold. The most potent analog, 5m, inhibits the pigment production of S. aureus Newman and three MRSA strains, with IC50 values of 0.38 5.45 nM, without any impact on the survival of four strains (up to 200 MUM). Notably, compound 5m (1 MUM) could significantly sensitize four strains to immune clearance and could effectively attenuate the virulence of three strains in vivo. Moreover, 5m was determined to be a weak antifungal reagent (MIC > 16 MUg/mL). Combined with good oral bioavailability (F = 42.2%) and excellent safety profiles, these data demonstrate that 5m may be a good candidate for the treatment of MRSA infections. PMID- 26999511 TI - Relationship between the Uncompensated Price Elasticity and the Income Elasticity of Demand under Conditions of Additive Preferences. AB - Income and price elasticity of demand quantify the responsiveness of markets to changes in income and in prices, respectively. Under the assumptions of utility maximization and preference independence (additive preferences), mathematical relationships between income elasticity values and the uncompensated own and cross price elasticity of demand are here derived using the differential approach to demand analysis. Key parameters are: the elasticity of the marginal utility of income, and the average budget share. The proposed method can be used to forecast the direct and indirect impact of price changes and of financial instruments of policy using available estimates of the income elasticity of demand. PMID- 26999510 TI - A simulated car-driving study on the effects of acute administration of levocetirizine, fexofenadine, and diphenhydramine in healthy Japanese volunteers. AB - OBJECTIVE: Antihistamines are often used for treating allergic rhinitis. However, many older antihistamines cause sedative side effects. The sedative effects of antihistamines on car-driving have been investigated. This has not been investigated for levocetirizine, a new-generation antihistamine, in Asian populations, and so we evaluated its sedative effects in healthy Japanese subjects. METHODS: In this double-blind, placebo-controlled, four-way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed. RESULTS: The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer-generation antihistamines in a manner that corresponds with subjective sedation. CONCLUSIONS: Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car-driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999512 TI - Implications of gambling problems for family and interpersonal adjustment: results from the Quinte Longitudinal Study. AB - AIMS: To evaluate (1) whether gambling problems predict overall trajectories of change in family or interpersonal adjustment and (2) whether annual measures of gambling problems predict time-specific decreases in family or interpersonal adjustment, concurrently and prospectively. DESIGN: The Quinte Longitudinal Study (QLS) involved random-digit dialling of telephone numbers around the city of Belleville, Canada to recruit 'general population' and 'at-risk' groups (the latter oversampling people likely to develop problems). Five waves of assessment were conducted (2006-10). Latent Trajectory Modelling (LTM) estimated overall trajectories of family and interpersonal adjustment, which were predicted by gambling problems, and also estimated how time-specific problems predicted deviations from these trajectories. SETTING: Southeast Ontario, Canada. PARTICIPANTS: Community sample of Canadian adults (n = 4121). MEASUREMENTS: The Problem Gambling Severity Index (PGSI) defined at-risk gambling (ARG: PGSI 1-2) and moderate-risk/problem gambling (MR/PG: PGSI 3+). Outcomes included: (1) family functioning, assessed using a seven-point rating of overall functioning; (2) social support, assessed using items from the Non-support subscale of the Personality Assessment Inventory; and (3) relationship satisfaction, measured by the Kansas Marital Satisfaction Scale. FINDINGS: Baseline measures of ARG and MR/PG did not predict rates of change in trajectories of family or interpersonal adjustment. Rather, the annual measures of MR/PG predicted time-specific decreases in family functioning (estimate: -0.11, P < 0.01), social support (estimate: -0.28, P < 0.01) and relationship satisfaction (estimate: -0.53, P < 0.01). ARG predicted concurrent levels of family functioning (estimate: -0.07, P < 0.01). There were time-lagged effects of MR/PG on subsequent levels of family functioning (estimate: -0.12, P < 0.01) and social support (estimate: -0.24, P < 0.01). CONCLUSIONS: In a longitudinal study of Canadian adults, moderate risk/problem gambling did not predict overall trajectories of family or interpersonal adjustment. Rather, the annual measures of moderate-risk/problem gambling predicted time-specific and concurrent decreases in all outcomes, and lower family functioning and social support across adjacent waves. PMID- 26999513 TI - Inhibitor or promoter? The performance of polysaccharides from Ganoderma lucidum on human tumor cells with different p53 statuses. AB - Polysaccharides from Ganoderma lucidum (GLPs) have been taken as effective supplements by both healthy people and cancer patients for many years. However, this short survey indicates that instead of inhibiting cancer cell growth, both submerge-cultured intracellular GLP and fruiting body GLP can stimulate the growth of human carcinoma cell lines lacking functional p53, such as HCT-116 p53( /-), Saos-2, H1299, HL-60, MDA-MB-157. Conversely, the two GLPs inhibit all other assayed cells with functional p53. These results could be an alert since mutational inactivation of the tumor suppressor protein p53 is the most frequent genetic alteration found in human tumors. PMID- 26999514 TI - Long-term emissions of hexabromocyclododecane as a chemical of concern in products in China. AB - There has been ever-increasing international interest in investigating the long term emissions of chemicals in products (CiPs) throughout their entire life cycle in the anthroposphere. Hexabromocyclododecane (HBCDD) is a contemporary example of special interest due to the recent listing of this hazardous flame retardant in the Stockholm Convention and the consequent need for parties to take appropriate measures to eliminate this compound. Here, we conducted a scenario based dynamic substance flow analysis, coupled with interval linear programming, to forecast the future HBCDD emissions in China in order to assist with the implementation of the Stockholm Convention in this current world's predominant HBCDD manufacturing and consuming country. Our results indicate that, under a business-as-usual scenario, the cumulative HBCDD production will amount to 238,000tonnes before its phase-out, 79% of which will be consumed in domestic market, accumulate as stocks in flame-retarded polystyrene insulation boards, and ultimately end up in demolition waste. While the production is scheduled to end in ca. 2021, emissions of HBCDD would continue until after 2100. For the entire simulation period 2000-2100, 44% of total cumulative emissions will arise from the industrial manufacture of HBCDD-associated end-products, whereas 49% will come from the end-of-life disposals of HBCDD-containing waste. The most effective end-of-life disposal option for minimizing emissions we found was, a pre demolition screening combined with complete incineration. Our study warns of the huge challenges that China would face in its eliminating HBCDD contamination in the following decades, and provides an effective methodology for a wider range of countries to recognize and tackle their long-term emission problems of hazardous CiPs. PMID- 26999515 TI - The influence of uncertainty and location-specific conditions on the environmental prioritisation of human pharmaceuticals in Europe. AB - The selection of priority APIs (Active Pharmaceutical Ingredients) can benefit from a spatially explicit approach, since an API might exceed the threshold of environmental concern in one location, while staying below that same threshold in another. However, such a spatially explicit approach is relatively data intensive and subject to parameter uncertainty due to limited data. This raises the question to what extent a spatially explicit approach for the environmental prioritisation of APIs remains worthwhile when accounting for uncertainty in parameter settings. We show here that the inclusion of spatially explicit information enables a more efficient environmental prioritisation of APIs in Europe, compared with a non-spatial EU-wide approach, also under uncertain conditions. In a case study with nine antibiotics, uncertainty distributions of the PAF (Potentially Affected Fraction) of aquatic species were calculated in 100*100km(2) environmental grid cells throughout Europe, and used for the selection of priority APIs. Two APIs have median PAF values that exceed a threshold PAF of 1% in at least one environmental grid cell in Europe, i.e., oxytetracycline and erythromycin. At a tenfold lower threshold PAF (i.e., 0.1%), two additional APIs would be selected, i.e., cefuroxime and ciprofloxacin. However, in 94% of the environmental grid cells in Europe, no APIs exceed either of the thresholds. This illustrates the advantage of following a location specific approach in the prioritisation of APIs. This added value remains when accounting for uncertainty in parameter settings, i.e., if the 95th percentile of the PAF instead of its median value is compared with the threshold. In 96% of the environmental grid cells, the location-specific approach still enables a reduction of the selection of priority APIs of at least 50%, compared with a EU wide prioritisation. PMID- 26999516 TI - Molecular subtyping and erythromycin resistance of Campylobacter in China. AB - AIMS: To investigate the erythromycin resistance patterns and mechanism for Campylobacter isolates in China. METHODS AND RESULTS: The minimum inhibitory concentrations of erythromycin on 858 Chinese Campylobacter isolates were analysed. PCR and DNA sequencing were used to identify mutations in the 23S rRNA and the presence of the ermB gene in the 158 erythromycin resistance isolates (18.4%). About 83% (131/158) had A2075G mutation in their 23S rRNA; no A2074C/G mutants were found. The ermB gene was identified in 30 Campylobacter coli isolates (19%). Four types of multidrug-resistant gene islands (MDRGIs) were found. Fifty-three types were identified by multilocus sequence typing among the resistant isolates. All isolates of STs 6322 and 1145 had the ermB gene. CONCLUSIONS: The erythromycin resistance rate of Camp. coli (58.56%) was much higher than Campylobacter jejuni (0.67%). The insertion sites between cadF and CCO1582 and between nfsB and cinA on the chromosome might be hot spots for MDRGI transformation. SIGNIFICANCE AND IMPACT OF THE STUDY: Point mutation in domain V of the 23S rRNA and the ermB gene accounted for 100% of the erythromycin resistance of Campylobacter in China. PMID- 26999517 TI - Association between SIRT1 Gene Polymorphisms and Breast Cancer in Egyptians. AB - BACKGROUND: Breast cancer is reported to cause the highest mortality among female cancer patients. Previous studies have explored the association of silent mating type information regulator 2 homolog 1 (SIRT1) gene expression with prognosis in breast cancer. However, no studies exist, so far, on the role of SIRT1 gene polymorphism in breast cancer risk or prognosis. The present study aimed to assess the association between SIRT1 gene polymorphisms and breast cancer in Egyptians. METHODS: The study comprised 980 Egyptian females divided into a breast cancer group (541 patients) and a healthy control group (439 subjects). SIRT1 gene single nucleotide polymorphisms (SNPs) rs3758391, rs3740051 and rs12778366 were genotyped using real-time polymerase chain reaction (RT-PCR). Allelic and genotypic frequencies were determined in both groups and association with breast cancer and clinicopathological characteristics was assessed. RESULTS: Breast cancer patients exhibited elevated serum SIRT1 levels which varied among different tumor grades. SIRT1 rs3758391 and rs12778366 TT genotypes were more frequent, exhibited higher SIRT1 levels than CC and CT genotypes and were associated with histologic grade and lymph node status. SIRT1 rs12778366 TT genotype also correlated with negative estrogen receptor (ER) and progesterone receptor (PR) statuses. The T allele frequency for both SNPs was higher in breast cancer patients than in normal subjects. Combined GG and AG genotypes of rs3740051 were more frequent, showed higher serum SIRT1 levels than the AA genotype, and were associated with ER and PR expression. Furthermore, inheritance of the G allele was associated with breast cancer. CONCLUSIONS: Our findings reveal that rs3758391 and rs12778366 polymorphisms of SIRT1 gene are associated with breast cancer risk and prognosis in the Egyptian population. PMID- 26999518 TI - Diversity of Bartonella and Rickettsia spp. in Bats and Their Blood-Feeding Ectoparasites from South Africa and Swaziland. AB - In addition to several emerging viruses, bats have been reported to host multiple bacteria but their zoonotic threats remain poorly understood, especially in Africa where the diversity of bats is important. Here, we investigated the presence and diversity of Bartonella and Rickettsia spp. in bats and their ectoparasites (Diptera and Siphonaptera) collected across South Africa and Swaziland. We collected 384 blood samples and 14 ectoparasites across 29 different bat species and found positive samples in four insectivorous and two frugivorous bat species, as well as their Nycteribiidae flies. Phylogenetic analyses revealed diverse Bartonella genotypes and one main group of Rickettsia, distinct from those previously reported in bats and their ectoparasites, and for some closely related to human pathogens. Our results suggest a differential pattern of host specificity depending on bat species. Bartonella spp. identified in bat flies and blood were identical supporting that bat flies may serve as vectors. Our results represent the first report of bat-borne Bartonella and Rickettsia spp. in these countries and highlight the potential role of bats as reservoirs of human bacterial pathogens. PMID- 26999519 TI - Selection criteria for surgical treatment of pudendal neuralgia. AB - AIMS: Pudendal neuralgia is the clinical expression of a chronic compression of the pudendal nerve. The diagnosis is based on a set of five criteria, called Nantes criteria. Four of the criteria are clinical and the last requires evaluation of the anesthetic response to CT-guided infiltration of the pudendal nerve. The aim of our study is to evaluate the relevance of anesthetic test response to select patients for surgery, and whether this criterion can be used to predict its success. METHODS: Retrospective analysis of a cohort of 34 patients undergoing surgical treatment. In our cohort, we included six patients with negative CT-guided pudendal nerve infiltration test. RESULTS: Of the 28 patients that met all five Nantes criteria, 64% (18 patients) responded well to surgery. In contrast, 100% of the six patients with a negative anesthetic test failed to show an amelioration of symptoms after surgical treatment (P = 0.006). In our analysis, there was no significant difference in surgery response when men were compared to women (P = 0.387), when procedure was unilateral or bilateral (P = 0.562), or when duration of symptoms was long (P = 0.412). We observed a difference in terms of age between the group of responders and non-responders, although this difference did not reach the threshold of significance (P = 0.216). CONCLUSIONS: The selection of candidates for surgery should always include a single diagnostic anesthetic injection of the pudendal nerve, as the fifth of the Nantes criteria is an effective predictor of the success of surgery. Neurourol. Urodynam. 36:663-666, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26999520 TI - Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study. AB - BACKGROUND: Alternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities. METHODS: We used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used. RESULTS: One person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls. CONCLUSIONS: We report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity. PMID- 26999521 TI - Fabrication of 3D porous SF/beta-TCP hybrid scaffolds for bone tissue reconstruction. AB - Bio-ceramic is a biomaterial actively studied in the field of bone tissue engineering. But, only certain ceramic materials can resolve the corrosion problem and possess the biological affinity of conventional metal biomaterials. Therefore, the recent development of composites of hybrid composites and polymers has been widely studied. In this study, we aimed to select the best scaffold of silk fibroin and beta-TCP hybrid for bone tissue engineering. We fabricated three groups of scaffold such as SF (silk fibroin scaffold), GS (silk fibroin/small granule size of beta-TCP scaffold) and GM (silk fibroin/medium granule size of beta-TCP scaffold), and we compared the characteristics of each group. During characterization of the scaffold, we used scanning electron microscopy (SEM) and a Fourier transform infrared spectroscopy (FTIR) for structural analysis. We compared the physiological properties of the scaffold regarding the swelling ratio, water uptake and porosity. To evaluate the mechanical properties, we examined the compressive strength of the scaffold. During in vitro testing, we evaluated cell attachment and cell proliferation (CCK-8). Finally, we confirmed in vivo new bone regeneration from the implanted scaffolds using histological staining and micro-CT. From these evaluations, the fabricated scaffold demonstrated high porosity with good inter-pore connectivity, showed good biocompatibility and high compressive strength and modulus. In particular, the present study indicates that the GM scaffold using beta-TCP accelerates new bone regeneration of implanted scaffolds. Accordingly, our scaffold is expected to act a useful application in the field of bone tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1779-1787, 2016. PMID- 26999522 TI - Executive Functioning and Learning Skills of Adolescent Children Born at Fewer than 26 Weeks of Gestation. AB - AIMS: To assess the cognitive and behavioral aspects of executive functioning (EF) and learning skills in extremely preterm (EPT) children compared with term control children aged 10 to 15 years. METHODS: A total of 132 of 134 (98% of all eligible survivors) EPT children born at the 2 Swedish regional tertiary care centers from 1992 to 1998 (mean age = 12 years, mean birth weight = 718 g, and mean gestational age = 24.4 weeks) and 103 matched term controls were assessed. General intelligence was assessed using the Wechsler Intelligence Scale for Children (WISC-III-R), and cognitive aspects of EF were analyzed using EF sensitive subscales of the WISC-III-R and Tower test of the Delis-Kaplan Executive Function Scale (D-KEFS). Behaviors related to EF and learning skills were assessed using the Five to Fifteen questionnaire, which is a validated parent and teacher instrument. Academic performance in school was assessed by teachers' responses on Achenbach's Teachers Report Form. Analyses performed included multivariate analyses of covariance (ANCOVA and MANCOVA) and logistic regression analyses. RESULTS: The EPT children displayed significant deficits in cognitive aspects of EF compared with the controls, exhibiting decreases on the order of 0.9 SD to 1.2 SD for tasks of verbal conceptual reasoning, verbal and non-verbal working memory, processing speed and planning ability (P <0.001 for all). After excluding the children with major neurosensory impairment (NSI) or a Full Scale intelligence quotient (FSIQ) of < 70, significant differences were observed on all tests. Compared with controls, parents and teachers of EPT children reported significantly more EF-related behavioral problems. MANCOVA of teacher-reported learning skills in children with FSIQ >70 and without major NSI revealed no interactions, but significant main effects were observed for the behavioral composite executive function score, group status (EPT vs control) and FSIQ, for which all effect sizes were medium to large. The corresponding findings of MANCOVA of the parent-reported learning skills were very similar. According to the teachers' ratings, the EPT children were less well adjusted to the school environment. CONCLUSION: EPT children born in the 1990s who received active perinatal care are at an increased risk of executive dysfunction, even after excluding children with significant neurodevelopmental disabilities. Even mild to moderate executive dysfunctions has a significant impact on learning skills. These findings suggest the need for timely interventions that address specific cognitive vulnerabilities and executive dysfunctions. PMID- 26999523 TI - Tissue engineering a human phalanx. AB - A principal purpose of tissue engineering is the augmentation, repair or replacement of diseased or injured human tissue. This study was undertaken to determine whether human biopsies as a cell source could be utilized for successful engineering of human phalanges consisting of both bone and cartilage. This paper reports the use of cadaveric human chondrocytes and periosteum as a model for the development of phalanx constructs. Two factors, osteogenic protein 1 [OP-1/bone morphogenetic protein-7 (BMP7)], alone or combined with insulin-like growth factor (IGF-1), were examined for their potential enhancement of chondrocytes and their secreted extracellular matrices. Design of the study included culture of chondrocytes and periosteum on biodegradable polyglycolic acid (PGA) and poly-l-lactic acid (PLLA)-poly-epsilon-caprolactone (PCL) scaffolds and subsequent implantation in athymic nu/nu (nude) mice for 5, 20, 40 and 60 weeks. Engineered constructs retrieved from mice were characterized with regard to genotype and phenotype as a function of developmental (implantation) time. Assessments included gross observation, X-ray radiography or microcomputed tomography, histology and gene expression. The resulting data showed that human cell-scaffold constructs could be successfully developed over 60 weeks, despite variability in donor age. Cartilage formation of the distal phalanx models enhanced with both OP-1 and IGF-1 yielded more cells and extracellular matrix (collagen and proteoglycans) than control chondrocytes without added factors. Summary data demonstrated that human distal phalanx models utilizing cadaveric chondrocytes and periosteum were successfully fabricated and OP-1 and OP-1/IGF-1 accelerated construct development and mineralization. The results suggest that similar engineering and transplantation of human autologous tissues in patients are clinically feasible. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999524 TI - Upregulated thymic stromal lymphopoietin receptor expression in children with asthma. AB - BACKGROUND: Thymic stromal lymphopoietin (TSLP) plays an important role in pathogenesis in patients with asthma. However, the role of thymic stromal lymphopoietin receptor (TSLPR) and correlation with IL-7Ralpha and clinical severity in asthmatic or nonasthmatic children remain unclear. We investigated TSLPR and IL-7Ralpha mRNuAlpha levels in asthma and nonasthma and assessed TSLPR expression in children who were sensitive to mites. MATERIALS AND METHODS: We enrolled asthmatic and nonasthmatic children. To minimize the influence of allergy, we also divided participants into following 4 groups: nonallergic and nonasthmatic group (NN) (healthy children), allergic but nonasthmatic group (AN), nonallergic but asthmatic group (NA) and allergic asthmatic group (AA). We drew blood samples to check total IgE, allergen-specific IgE and TSLP and measured the expression of the TSLPR and IL-7Ralpha genes using reverse-transcription polymerase chain reaction (RT-PCR) and real-time PCR. Asthma symptom score was also recorded. RESULTS: Thymic stromal lymphopoietin and TSLPR levels were found to be significantly higher in asthmatic than in nonasthmatic children. The levels of TSLP were found to be significantly different between AA and NN groups (P < 0.05). TSLPR expression in NA and AA groups was found to be significantly higher than in NN group (P < 0.05). TSLPR did not differ significantly between NA and AA groups. The TSLPR expression correlated strongly with IL-7Ralpha and weakly with mite-specific IgE. Clinical asthmatic severity of children was found to exert no influence on TSLPR level. CONCLUSION: Thymic stromal lymphopoietin receptor might be a significant disease biomarker for asthma. The levels of TSLPR were found to be higher in asthmatic patients than in healthy children, but were found to be not different between allergic and nonallergic asthmatic patients. PMID- 26999525 TI - Identification of QTL for Early Vigor and Stay-Green Conferring Tolerance to Drought in Two Connected Advanced Backcross Populations in Tropical Maize (Zea mays L.). AB - We aimed to identify quantitative trait loci (QTL) for secondary traits related to grain yield (GY) in two BC1F2:3 backcross populations (LPSpop and DTPpop) under well-watered (4 environments; WW) and drought stressed (6; DS) conditions to facilitate breeding efforts towards drought tolerant maize. GY reached 5.6 and 5.8 t/ha under WW in the LPSpop and the DTPpop, respectively. Under DS, grain yield was reduced by 65% (LPSpop) to 59% (DTPpop) relative to WW. GY was strongly associated with the normalized vegetative index (NDVI; r ranging from 0.61 to 0.96) across environmental conditions and with an early flowering under drought stressed conditions (r ranging from -0.18 to -0.25) indicative of the importance of early vigor and drought escape for GY. Out of the 105 detected QTL, 53 were overdominant indicative of strong heterosis. For 14 out of 18 detected vigor QTL, as well as for eight flowering time QTL the trait increasing allele was derived from CML491. Collocations of early vigor QTL with QTL for stay green (bin 2.02, WW, LPSpop; 2.07, DS, DTPpop), the number of ears per plant (bins 2.02, 2.05, WW, LPSpop; 5.02, DS, LPSpop) and GY (bin 2.07, WW, DTPpop; 5.04, WW, LPSpop), reinforce the importance of the observed correlations. LOD scores for early vigor QTL in these bins ranged from 2.2 to 11.25 explaining 4.6 (additivity: +0.28) to 19.9% (additivity: +0.49) of the observed phenotypic variance. A strong flowering QTL was detected in bin 2.06 across populations and environmental conditions explaining 26-31.3% of the observed phenotypic variation (LOD: 13-17; additivity: 0.1-0.6d). Improving drought tolerance while at the same time maintaining yield potential could be achieved by combining alleles conferring early vigor from the recurrent parent with alleles advancing flowering from the donor. Additionally bin 8.06 (DTPpop) harbored a QTL for GY under WW (additivity: 0.27 t/ha) and DS (additivity: 0.58 t/ha). R2 ranged from 0 (DTPpop, WW) to 26.54% (LPSpop, DS) for NDVI, 18.6 (LPSpop, WW) to 42.45% (LPSpop, DS) for anthesis and from 0 (DTPpop, DS) to 24.83% (LPSpop, WW) for GY. Lines out-yielding the best check by 32.5% (DTPpop, WW) to 60% (DTPpop, DS) for all population-by-irrigation treatment combination (except LPSpop, WW) identified are immediately available for the use by breeders. PMID- 26999526 TI - Compliance, Persistence, and Preferences Regarding Osteoporosis Treatment During Active Therapy or Drug Holiday. AB - Osteoporosis treatments reduce the risk of fractures by 30%-50%, but adherence after 1 year is only about 50%. Drug holiday, a period with no active treatment, is part of routine management. The objective of this study was to determine compliance and persistence with osteoporosis therapy among postmenopausal women and to assess attitudes regarding treatment resumption among patients on drug holiday. This was a prospective observational study of patients followed at a dedicated metabolic bone clinic September 2013-February 2014. Compliance was assessed by medication possession ratio (MPR; number of doses dispensed relative to the number prescribed). Persistence was defined as continuation of treatment without a >30-day gap in prescription refills. Of 150 patients (70.1 +/- 8.1 years), 57% were prescribed a medication: 64% oral, mostly bisphosphonates. MPR >= 80% was found in 80% and <50% in 12%; it was 100% for zoledronic acid and denosumab and 97%, 85%, 83%, and 70% for raloxifene, teriparatide, oral bisphosphonates, and strontium ranelate, respectively. Of 39 patients prescribed oral bisphosphonates, 77% persisted with treatment, and 89% took them as directed. Of 64 patients on a drug holiday, 59% expressed confidence in their physician's future treatment choice, whereas 19% expressed concerns about resuming treatment. Compliance among patients attending a dedicated bone clinic was higher than that reported in the literature. High persistence and compliance may be specific to patients followed in this type of setting. This study provides new information about attitudes of patients on a drug holiday. Most were not concerned about resuming treatment and did not have a preferred medication. PMID- 26999527 TI - Synthesis of Cyclohexane-Fused Isocoumarins via Cationic Palladium(II)-Catalyzed Cascade Cyclization Reaction of Alkyne-Tethered Carbonyl Compounds Initiated by Intramolecular Oxypalladation of Ester-Substituted Aryl Alkynes. AB - A cationic Pd(II)-catalyzed cascade cyclization reaction of alkyne-tethered carbonyl compounds was developed. This reaction is initiated by intramolecular oxypalladation of alkynes with an ester group followed by 1,2-addition of the formed C-Pd(II) bond to the carbonyl group, providing a highly efficient method for the synthesis of cyclohexane-fused isocoumarins. PMID- 26999528 TI - Comparative analysis of clinical outcomes between zero-profile implant and cages with plate fixation in treating multilevel cervical spondilotic myelopathy: A three-year follow-up. AB - OBJECTIVES: This study aimed to figure out three-year clinical outcomes and complications of ACDF with Zero-p in treating multilevel cervical spondylotic myelopathy (MCSM) by comparing with plate fixation. CLINICAL MATERIALS AND METHODS: Patients with MCSM caused by degenerative disc herniation only were recruited from April 2010 to December 2010. According to the surgical procedures, the patients were divided into two groups at random, the plate group and Zero-P group. The data was collected before surgery and at three-year follow-up. Clinical parameters, including Japanese orthopedic association (JOA) score, neck disabled index (NDI) were evaluated. Cervical segmental lordosis was calculated and fusion in each level was assessed on lateral radiographs. The Bazaz's criterion and the short Swallowing and Quality of Life (SQOL) questionnaires were used to evaluate the dysphagia incidence and severity respectively. The presence of ALOD was observed and recorded on lateral radiographs. RESULTS: A total of 72 patients (46 men and 26 women) were recruited. The mean age at operation was 52.9+/-7.9years, ranged from 43 to 69 years. There was no significant difference between two groups preoperatively in age, sex, operative levels, JOA, NDI, cervical lordosis, dysphagia incidence, SQOL and ALOD incidence. JOA, NDI and cervical lordosis improved postoperatively and postoperative SQOL got restitution in both groups. However, no difference was detected. There were 7 patients with ALOD in the plate group after surgeries while there was only 1 patient in Zero-P group. The difference of AOLD incidence between them was significant. Of the 7 patients with ALOD in the plate group, 4 patients developed ALOD in cranial level, 2 in caudal level and 1 in both levels. The patient in Zero-P group developed ALOD in caudal level. CONCLUSION: Based on the three-year follow-up, we could not conclude that Zero-P was superior to plate fixation in clinical outcomes such as neurological results, cervical lordosis, fusion rate and the incidence and severity of dysphagia in treating MCSM. However, it had the advantage of reducing ALOD incidence which tended to happen in ACDF with plate fixation. PMID- 26999529 TI - Pyogenic cerebral abscesses demonstrating facilitated diffusion. AB - OBJECTIVE: Pyogenic cerebral abscesses are associated with high morbidity and mortality when treatment is delayed. Benign clinical presentation, as well as absence of restricted diffusion on MRI may contribute to missed diagnoses and delays. The authors sought to elucidate characteristics associated with facilitated diffusion on the MRIs of patients with pyogenic abscesses. PATIENTS AND METHODS: The authors performed a 10-year retrospective review of prospectively attained data for patients undergoing mass resection by a single surgeon. RESULTS: Our findings show that 3/33 (9%) patients with microbiological diagnoses of cerebral abscesses with a thin ring of contrast enhancement but minimal or no restricted diffusion MRI imaging. All causative organisms were hemolytic streptococci and none of the subjects received antibiotic therapy prior to specimen collection. A trend in these patients was the presence of diabetes and in conjunction with other studies that cite incomplete treatment as being associated with facilitated diffusion, we conjecture that impaired inflammatory responses in some patients may be associated with the absence of restricted diffusion. CONCLUSION: With this in mind, clinicians must maintain a high index of suspicion when assessing patients with cystic, contrast enhancing masses. A prospective multicenter study to compile imaging along with other patient characteristics may help refine the non-invasive diagnostic criteria for brain abscesses. PMID- 26999530 TI - Molecular and clinical prognostic factors for favorable outcome following surgical resection of adult intramedullary spinal cord astrocytomas. AB - OBJECTIVE: Intramedullary spinal cord astrocytomas are uncommon but important entities. Aggressive surgical resection is believed to be critical to prevent subsequent neurological deterioration; however, the prognostic significance of numerous patient and molecular variables remains unclear. We sought to investigate the clinical and molecular factors associated with outcomes following surgical resection of adult spinal cord astrocytomas. METHODS: A consecutive retrospective chart review of all patients who underwent intramedullary spinal cord astrocytoma resection at a single tertiary-care institution between January 1996 and December 2011 was conducted. Molecular data collected included p53 mutation status, proliferative activity (Ki-67), 1p/19q chromosome loss, and EGFR amplification. Multivariable logistic and Cox proportional hazards regression were used to identify variable associated with postoperative outcomes. RESULTS: Among 13 patients undergoing surgical resection followed for a median of 54 months, 54% experienced improvement in neurological status, while 15% remained unchanged and 31% deteriorated. Following resection, the 5-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83%, 63%, and 83%. Median PFS time was found to be 5.6 years. Multivariable regression revealed limited characteristics associated with postoperative outcomes, though no molecular characteristics were found to be prognostic. Older age at surgery predicted decreased probability of PFS (HR 0.91, 95% CI 0.81-0.99, p=0.03) and trended towards predicting lack of neurological improvement (OR 0.94, 95% CI 0.83 1.02, p=0.21) and decreased OS (HR 0.93, 95% CI 0.81, 1.03, p=0.15). Preoperative motor symptoms (OR 0.12, 95% CI <0.01-1.91, p=0.14) and adjuvant chemotherapy (OR 0.07, 95% CI <0.01-1.82, p=0.12) also trended towards predicting lack of neurological improvement. CONCLUSION: Age was the only patient variable found to have a statistically significant association with profession-free survival and no other factors were significantly associated with postoperative outcomes. These findings were limited by a relatively small sample size; thus, future studies with increased power investigating the prognostic effects of molecular characteristics could provide further clarity in identifying patients most likely to benefit from surgical resection. PMID- 26999531 TI - MTH1 Substrate Recognition--An Example of Specific Promiscuity. AB - MTH1 (NUDT1) is an oncologic target involved in the prevention of DNA damage. We investigate the way MTH1 recognises its substrates and present substrate-bound structures of MTH1 for 8-oxo-dGTP and 8-oxo-rATP as examples of novel strong and weak binding substrate motifs. Investigation of a small set of purine-like fragments using 2D NMR resulted in identification of a fragment with weak potency. The protein-ligand X-Ray structure of this fragment provides insight into the role of water molecules in substrate selectivity. Wider fragment screening by NMR resulted in three new protein structures exhibiting alternative binding configurations to the key Asp-Asp recognition element of the protein. These inhibitor binding modes demonstrate that MTH1 employs an intricate yet promiscuous mechanism of substrate anchoring through its Asp-Asp pharmacophore. The structures suggest that water-mediated interactions convey selectivity towards oxidized substrates over their non-oxidised counterparts, in particular by stabilization of a water molecule in a hydrophobic environment through hydrogen bonding. These findings may be useful in the design of inhibitors of MTH1. PMID- 26999533 TI - Factors That Influence Running Intensity in Interchange Players in Professional Rugby League. AB - BACKGROUND: Rugby league coaches adopt replacement strategies for their interchange players to maximize running intensity; however, it is important to understand the factors that may influence match performance. PURPOSE: To assess the independent factors affecting running intensity sustained by interchange players during professional rugby league. METHODS: Global positioning system (GPS) data were collected from all interchanged players (starters and nonstarters) in a professional rugby league squad across 24 matches of a National Rugby League season. A multilevel mixed-model approach was employed to establish the effect of various technical (attacking and defensive involvements), temporal (bout duration, time in possession, etc), and situational (season phase, recovery cycle, etc) factors on the relative distance covered and average metabolic power (Pmet) during competition. Significant effects were standardized using correlation coefficients, and the likelihood of the effect was described using magnitude-based inferences. RESULTS: Superior intermittent running ability resulted in very likely large increases in both relative distance and Pmet. As the length of a bout increased, both measures of running intensity exhibited a small decrease. There were at least likely small increases in running intensity for matches played after short recovery cycles and against strong opposition. During a bout, the number of collision-based involvements increased running intensity, whereas time in possession and ball time out of play decreased demands. CONCLUSIONS: These data demonstrate a complex interaction of individual- and match-based factors that require consideration when developing interchange strategies, and the manipulation of training loads during shorter recovery periods and against stronger opponents may be beneficial. PMID- 26999534 TI - Inhibition of the STAT3 Protein by a Dinuclear Macrocyclic Complex. AB - A new diethylenetriamine-derived macrocycle bearing 2-methylpyridyl arms and containing m-xylyl spacers, L, was prepared, and its dinuclear copper(II) and zinc(II) complexes were used as receptors for the recognition in aqueous solution of a phosphorylated peptide derived from a sequence of the STAT3 protein. A detailed study of the acid-base behavior of L and of its complexation properties as well as of the association of the phosphorylated peptide to the receptor was carried out by potentiometry in aqueous solution at 298.2 K and I = 0.10 M in KNO3. The data revealed that the receptor forms stable associations with several protonated forms of the substrate, with constant values ranging from 3.32 to 4.25 log units. The affinity of the receptor for the phosphorylated substrate studied is higher at a pH value where the receptor is mainly in the [Cu2L](4+) form and the pY residue of the substrate is in the dianionic form (pH 6.55). These results, also supported by (31)P NMR studies, showed that the phosphopeptide is bound through the phosphoryl group in a bridging mode. Additionally, the receptor inhibited binding between active (phosphorylated) STAT3 and its target DNA sequence in a dose-dependent manner (IC50 63 +/- 3.4 MUM) in human nuclear extracts in vitro. Treatment of whole cells with the inhibitor revealed that it is bioactive in living cells and has oncostatic properties that could be interesting for the fight against cancer and other pathologies involving the STAT3 protein. PMID- 26999532 TI - Cervicovaginal and Rectal Fluid as a Surrogate Marker of Antiretroviral Tissue Concentration: Implications for Clinical Trial Design. AB - BACKGROUND: Quantifying tissue drug concentrations can yield important information during drug development, but complicates pharmacokinetic study design. Mucosal fluids collected by direct aspiration (cervicovaginal fluid; CVF) or swab (rectal fluid; RF) might be used as tissue concentration surrogates, but these relationships are not well characterized. METHODS: Forty-nine healthy women, given a single oral dose of tenofovir, maraviroc, emtricitabine, or raltegravir at 50%-200% of the treatment dose, provided 13 plasma, 12 CVF, 12 RF and one cervical, vaginal and rectal tissue biopsy over 48 hours. Relationships between these paired samples were characterized by linear and multiple linear regression. Adjusted r values were used to select the final predictive models. RESULTS: CVF exposure increased linearly with dose for all antiretrovirals (r(2) >= 0.23, P <= 0.02) except raltegravir (r(2) = 0.08, P = 0.19). In RF, only emtricitabine increased linearly with dose (r(2) = 0.27, P = 0.01). For all antiretrovirals, CVF and RF concentrations significantly correlated with mucosal tissue concentrations (female genital tract r(2) >= 0.37, rectal tissue (2)r >= 0.50, P <= 0.001). In the final multivariate models, plasma and fluid concentrations were both associated with FGT concentrations for all antiretrovirals (r(2) >= 0.81, P < 0.001). The same was noted for rectal tissue (r(2) >= 0.58, P < 0.001) except for tenofovir, for which RF alone was predictive of tissue concentration (r(2) = 0.91, P < 0.001). CONCLUSIONS: Mucosal fluids were positively correlated with tissue concentrations and including plasma concentrations improved the regression models in most cases. Dose linearity in CVF, but not RF, suggests a saturation process in lower gastrointestinal tract tissue. These findings suggest that mucosal fluid and plasma concentrations may be used for qualitative inference of tissue concentrations for these antiretrovirals. PMID- 26999536 TI - Physicians Abstracts. PMID- 26999537 TI - Working Parties. PMID- 26999535 TI - Running speed increases plantar load more than per cent body weight on an AlterG(r) treadmill. AB - AlterG(r) treadmills allow for running at different speeds as well as at reduced bodyweight (BW), and are used during rehabilitation to reduce the impact load. The aim of this study was to quantify plantar loads borne by the athlete during rehabilitation. Twenty trained male participants ran on the AlterG(r) treadmill in 36 conditions: all combinations of indicated BW (50-100%) paired with different walking and running speeds (range 6-16 km . hr-1) in a random order. In shoe maximum plantar force (Fmax) was recorded using the Pedar-X system. Fmax was lowest at the 6 km . hr-1 at 50% indicated BW condition at 1.02 +/- 0.21BW and peaked at 2.31 +/- 0.22BW for the 16 km . hr-1 at 100% BW condition. Greater increases in Fmax were seen when increasing running speed while holding per cent BW constant than the reverse (0.74BW-0.91BW increase compared to 0.19-0.31BW). A table is presented with each of the 36 combinations of BW and running speed to allow a more objective progression of plantar loading during rehabilitation. Increasing running speed rather than increasing indicated per cent BW was shown to have the strongest effect on the magnitude of Fmax across the ranges of speeds and indicated per cent BWs examined. PMID- 26999538 TI - Physicians Poster SessionsPoster Session / Day 1. PMID- 26999539 TI - Physicians Poster SessionsPoster session / Day 2. PMID- 26999540 TI - The Nurses Group Oral Sessions. PMID- 26999541 TI - The Nurses Group Poster Session. PMID- 26999542 TI - The Data Management Group. PMID- 26999543 TI - The Quality Management Group Oral Session. PMID- 26999544 TI - The Quality Management Group Poster Session. PMID- 26999545 TI - Statistical Symposium Oral Presentations. PMID- 26999546 TI - Publication Only. PMID- 26999548 TI - Residual symptoms and functionality in depressed outpatients: A one-year observational study in Switzerland with escitalopram. AB - BACKGROUND: Residual depressive symptoms are associated with a poor prognosis for relapse or recurrence and are recognized as impeding factors of functionality. Recovery to the pre-depression level of functioning should be the goal of treatment. AIM: To evaluate outcomes in depressed outpatients treated with escitalopram regarding response, recovery, residual symptoms, functionality and ability to work over 48 weeks. METHOD: 3278 outpatients were evaluated at weeks 8, 24 and 48. A simple questionnaire was used to rate severity of illness, impairment of functionality, treatment response, tolerability, presence and severity of residual symptoms, whether remission with residual symptoms or recovery was achieved, and to what degree the patient was able to work. RESULTS: Data over the full 48-week period were available for 75.8% of patients, for whom treatment response was rated as "very good" or "good" in 81%. However, only 42% of the completing patients achieved recovery without residual symptoms, while 41% were rated as remitters with residual symptoms. Lack of energy/motivation was the most common reported residual symptom and was present in 23.5% of patients at study end. Concentration difficulties were present in 15.8% and impaired sleep in 13.9% of patients. Complete inability to work decreased from 36% at baseline to 9% at week 48, while full-time working capacity increased from 37% to 62%. LIMITATIONS: Non-controlled observational real life study using simple ratings rather than established rating scales. CONCLUSION: <50% of patients completing a one-year antidepressant treatment regimen were rated as being symptomatically fully recovered, and ~50% still reported functional deficits. PMID- 26999550 TI - The prevalence and predictors of obstructive sleep apnea in major depressive disorder, bipolar disorder and schizophrenia: A systematic review and meta analysis. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a health hazard since it is associated with neurocognitive dysfunction and cardio-metabolic diseases. The prevalence of OSA among people with serious mental illness (SMI) is unclear. METHOD: We searched major electronic databases from inception till 06/2015. Articles were included that reported the prevalence of OSA determined by polysomnography (PSG) or an apnea-hypopnea index (AHI) >5 events/hr, in people with major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia. A random effects meta-analysis calculating the pooled prevalence of OSA and meta regression of potential moderators were performed. RESULTS: Twelve articles were included representing 570,121 participants with SMI (mean age=38.3 years (SD=7.5)), 45.8% male (range=32-80.4) and mean body mass index (BMI) 25.9 (SD=3.7). The prevalence of OSA in SMI in clinical studies was 25.7% (95% CI 13.9 to 42.4%, n=1,535). Higher frequencies of OSA were seen in MDD (36.3%, 19.4 57.4%, n=525) than in BD (24.5%, 95% CI 10.6-47.1, n=681) and schizophrenia (15.4%, 95% CI 5.3-37.1%, n=329). The prevalence of OSA in 568,586 people with SMI from population cohort studies was 10.7% (95% CI 2.4-37.0%) and 19.8% (95% CI 2.5-70.0%) in 358,853 people with MDD. Increasing age (beta=0.063, 95% CI 0.0005 0.126, p=0.04, N=10) and BMI predicted increased prevalence of OSA (beta=0.1642, 95% CI 0.004-0.3701, p=0.04, N=9). CONCLUSION: People with SMI (particularly MDD) have a high prevalence of OSA. Screening for and interventions to manage OSA in SMI including those focused on reducing BMI are warranted. PMID- 26999551 TI - The Challenges of Mobile Health Regulation. PMID- 26999549 TI - Pregnancy-related anxiety: Evidence of distinct clinical significance from a prospective longitudinal study. AB - BACKGROUND: Pregnancy-related anxiety (PrA) has attracted considerable research attention, but questions remain about its distinctiveness from conventional constructs and measures. In a high psychosocial risk, ethnically diverse sample, we examine the degree to which PrA is distinct from continuous and diagnostic measures of anxiety and worry in terms of longitudinal course, associations with psychosocial and perinatal risk, and prediction of postnatal mood disturbance. METHODS: 345 women oversampled for prenatal anxiety and depression were selected from an urban obstetrics clinic serving a predominantly low-income, ethnically diverse population. PrA was assessed at 20 and 32 weeks gestation; anxiety and depression symptoms were assessed from questionnaire and from clinical interview at 20 and 32 weeks gestation and again at 2 and 6 months postnatally. Data relevant to psychosocial and obstetric risks were ascertained from interview, medical exam, and chart review. RESULTS: Two distinct factors of PrA were identified, indexing specific concerns about the child's health and about the birth; these two PrA factors showed distinct longitudinal patterns in the prenatal period, and modest associations with general measures of anxiety and depression from questionnaire and clinical interview. PrA was also distinguished from conventional symptom measures in its associated features and prediction of birth weight and postnatal mood. LIMITATIONS: The sample was at high psychosocial risk and ethnically diverse; findings may not generalize to other samples. CONCLUSIONS: PrA can be distinguished from general measures of anxiety in pregnancy in terms of longitudinal course, associated features, and prediction to postnatal mood disturbance, and may warrant specific clinical attention. PMID- 26999552 TI - Apnea-hypopnea index estimation using quantitative analysis of sleep macrostructure. AB - Obstructive sleep apnea, characterized by recurrent cessation or substantial reduction in breathing during sleep, is a prevalent and serious medical condition. Although a significant relationship between obstructive sleep apnea and sleep macrostructure has been revealed in several studies, useful applications of this relationship have been limited. The aim of this study was to suggest a novel approach using quantitative analysis of sleep macrostructure to estimate the apnea-hypopnea index, which is commonly used to assess obstructive sleep apnea. Without being bound by conventional sleep macrostructure parameters, various new sleep macrostructure parameters were extracted from the polysomnographic recordings of 132 subjects. These recordings were split into training and validation sets, each with 66 recordings including 48 recordings with an apnea-hypopnea index greater than 5 events h(-1). The nonlinear regression analysis, performed using the percentage transition probability from non-rapid eye movement sleep stage 2 to stage 1, was most effective in estimating the apnea-hypopnea index. Between the apnea-hypopnea index estimates and the reference values reported from polysomnography, a root mean square error of 7.30 events h(-1) was obtained in the validation set. At an apnea-hypopnea index cut off of ?30 events h(-1), the obstructive sleep apnea diagnostic performance was provided with a sensitivity of 90.0%, a specificity of 93.5%, and an accuracy of 92.4% by our method. The developed apnea-hypopnea index estimation model has the potential to be utilized in circumstances in which it is not possible to acquire or analyze respiration signal but it is possible to obtain information on sleep macrostructure. PMID- 26999553 TI - On variance estimate for covariate adjustment by propensity score analysis. AB - Propensity score (PS) methods have been used extensively to adjust for confounding factors in the statistical analysis of observational data in comparative effectiveness research. There are four major PS-based adjustment approaches: PS matching, PS stratification, covariate adjustment by PS, and PS based inverse probability weighting. Though covariate adjustment by PS is one of the most frequently used PS-based methods in clinical research, the conventional variance estimation of the treatment effects estimate under covariate adjustment by PS is biased. As Stampf et al. have shown, this bias in variance estimation is likely to lead to invalid statistical inference and could result in erroneous public health conclusions (e.g., food and drug safety and adverse events surveillance). To address this issue, we propose a two-stage analytic procedure to develop a valid variance estimator for the covariate adjustment by PS analysis strategy. We also carry out a simple empirical bootstrap resampling scheme. Both proposed procedures are implemented in an R function for public use. Extensive simulation results demonstrate the bias in the conventional variance estimator and show that both proposed variance estimators offer valid estimates for the true variance, and they are robust to complex confounding structures. The proposed methods are illustrated for a post-surgery pain study. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999554 TI - Private Practice of Prosthodontists in the United States: Results from the 2008, 2011, and 2014 Surveys of Prosthodontists. AB - PURPOSE: To review data and results from past surveys of prosthodontists sponsored and conducted by the American College of Prosthodontists (ACP). Specifically, most results are examined and presented from the surveys conducted in 2008, 2011, and 2014. Selected survey results are examined for prosthodontists in private practice. MATERIALS AND METHODS: Results from past surveys of prosthodontists were statistically examined and used to estimate several characteristics of the current population of practicing prosthodontists. The selected characteristics included age, gender, number of patient visits, hours in the practice, employment of staff, referral sources, and financial conditions (e.g., gross receipts, expenses in the practice, and net income of prosthodontists). While the most recent survey was conducted during the year 2014, the respondents reported survey data for the previous year of 2013. RESULTS: The average age of a private practice prosthodontist in 2013 reached 52 years; 26 years since graduation from dental school and 20 years since completion of residency; an average of 20 years since starting practice as a prosthodontist, with 52.2% in solo practice. The mean number of hours per week in the practice was 32.6 hours, and practicing prosthodontists treated an average of 33 patient visits per week. The single largest source of referrals is the prosthodontist's patients, while general practitioners are a close second source of referrals. The largest percentage of time spent treating patients is for fixed prosthodontics (21%), which has declined from a mean of 24.1% reported in 2007. The mean amount of nominal gross billings in 2013 was $654,270 per prosthodontist, which was lower than the mean gross billings in both 2007 and 2010; average total practice expenses were $577,480; and the mean nominal net earnings in 2013 of prosthodontists in private practice was $225,280. CONCLUSION: Changes have continued to take place in the private practice of prosthodontics during most of the last decade. The prosthodontist private practice industry, not unlike dentistry as a whole, has undergone economic and practice challenges that have affected the conditions of the private practice of prosthodontists. PMID- 26999555 TI - Image Diagnosis: Capitellar Fracture. PMID- 26999558 TI - Degrading emotional memories induced by a virtual reality paradigm. AB - BACKGROUND AND OBJECTIVES: In Eye Movement and Desensitization and Reprocessing (EMDR) therapy, a dual-task approach is used: patients make horizontal eye movements while they recall aversive memories. Studies showed that this reduces memory vividness and/or emotionality. A strong explanation is provided by working memory theory, which suggests that other taxing dual-tasks are also effective. Experiment 1 tested whether a visuospatial task which was carried out while participants were blindfolded taxes working memory. Experiment 2 tested whether this task degrades negative memories induced by a virtual reality (VR) paradigm. METHODS: In experiment 1, participants responded to auditory cues with or without simultaneously carrying out the visuospatial task. In experiment 2, participants recalled negative memories induced by a VR paradigm. The experimental group simultaneously carried out the visuospatial task, and a control group merely recalled the memories. Changes in self-rated memory vividness and emotionality were measured. RESULTS: The slowing down of reaction times due to the visuospatial task indicated that its cognitive load was greater than the load of the eye movements task in previous studies. The task also led to reductions in emotionality (but not vividness) of memories induced by the VR paradigm. LIMITATIONS: Weaknesses are that only males were tested in experiment 1, and the effectiveness of the VR fear/trauma induction was not assessed with ratings of mood or intrusions in experiment 2. CONCLUSIONS: The results suggest that the visuospatial task may be applicable in clinical settings, and the VR paradigm may provide a useful method of inducing negative memories. PMID- 26999557 TI - Low holo-transcobalamin levels are prevalent in vegetarians and is associated with coronary artery disease in Indian population. AB - Coronary artery disease (CAD) has been increasing alarmingly in India. We had earlier shown that vitamin B12 deficiency is associated with CAD in Indian population. However, only about a quarter of the total vitamin B12 is internalised in the cells by the proteins transcobalamin II. Vitamin B12-bound transcobalamin II (holotranscobalamin, holoTC) is thus referred to as biologically active B12. In this study, we ascertained the levels of holoTC in 501 CAD cases and 1253 healthy controls and for the first time show that holoTC levels are significantly lower (p = 2.57E-4) in CAD (26.81 pmol/l) cases as compared to controls (29.97 pmol/l). PMID- 26999556 TI - Choreography of molecular movements during ribosome progression along mRNA. AB - During translation elongation, ribosome translocation along an mRNA entails rotations of the ribosomal subunits, swiveling motions of the small subunit (SSU) head and stepwise movements of the tRNAs together with the mRNA. Here, we reconstructed the choreography of the collective motions of the Escherichia coli ribosome during translocation promoted by elongation factor EF-G, by recording the fluorescence signatures of nine different reporters placed on both ribosomal subunits, tRNA and mRNA. We captured an early forward swiveling of the SSU head taking place while the SSU body rotates in the opposite, clockwise direction. Backward swiveling of the SSU head starts upon tRNA translocation and continues until the post-translocation state is reached. This work places structures of translocation intermediates along a time axis and unravels principles of the motions of macromolecular machines. PMID- 26999559 TI - Morphology and small subunit rRNA gene sequence of Uronemita parabinucleata n. sp. (Ciliophora, Uronematidae), with an improved generic diagnosis. AB - The morphology and infraciliature of a new species, Uronemita parabinucleata n. sp., isolated from intertidal sediments in a coastal region in northern China, were investigated using live observation and silver impregnation methods. The new species is characterized by an in vivo body size of about 20-50*10-25MUm, 22 or 23 somatic kineties, two macronuclear nodules, and one caudal cilium. Its small subunit ribosomal RNA gene (SSU rDNA) was sequenced and compared with those of other Uronemita species to reveal nucleotide differences. Phylogenetic analyses indicated that Uronemita is monophyletic and that the new species clusters with its congener Uronemita filificum, with full support provided by both Bayesian inference and maximum likelihood algorithms. Based on previous studies and the present study, an improved diagnosis of the genus Uronemita is supplied, which has been absent since the establishment of this genus. A key to the Uronemita species is also provided. PMID- 26999560 TI - Investigating the role of Acanthamoeba polyphaga in protecting Human Adenovirus from water disinfection treatment. AB - Human adenoviruses are responsible for a wide range of clinical infections and are present in aquatic environments, including river, seawater, drinking-water and sewage. Free-living amoebae (Acanthamoeba) in the same environments may internalize them and other microorganisms can act as a reservoir for the internalized viruses. In this study, we studied the interaction between Acanthamoeba polyphaga and Human Adenovirus type 5 (HAdV 5) to determine whether the amoeba played a role in protecting the internalized viruses from chemical disinfection. The efficacy of sodium hypochlorite disinfection against A. polyphaga and HAdV 5 either singly or in combination was assessed at three different concentrations. Individually, the amoeba were more resistant to chemical disinfection than HAdV 5 and remained alive after exposure to 5mg/l of sodium hypochlorite. In contrast, HAdV 5 lost infectivity following exposure to 2.5mg/l of sodium hypochlorite. When the amoeba and HAdV 5 were co-cultured, infectious virus was found in the cytoplasm of the amoeba at 5mg/l disinfectant concentration. These findings suggest that the A. polyphaga is providing protection for the HAdV 5. PMID- 26999561 TI - PCSK9 Inhibitors: Lots of Work Done, Lots More to Do. PMID- 26999563 TI - Hospital costs associated with thyroidectomy performed with a Harmonic device compared to conventional techniques: a systematic review and meta-analysis. AB - OBJECTIVES: Harmonic devices have become a world-wide standard for dissection and hemostasis in thyroidectomy. Numerous systematic reviews have reported superior operating times, blood loss, post-operative pain, length of stay, and overall safety outcomes. What has not been extensively evaluated in a robust manner is their economic impact. The purpose of this study is to evaluate the hospital costs associated with open thyroidectomy using Harmonic devices compared with conventional techniques for hemostasis. METHODS: A systematic review of Medline, Scopus, and CENTRAL was performed from January 1, 2000 to May 23, 2014 without language restrictions for randomized clinical trials comparing Harmonic surgical devices to conventional methods in thyroidectomy. The main outcome measure was total reported costs. Costs were pooled using the ratio of means and a random effects model. Sensitivity analyses assessed whether differences in patient and trial characteristics, healthcare setting, or choice of statistical model affected outcomes. RESULTS: Seven studies met the inclusion criteria. A total of 476 participants had procedures performed with Harmonic devices and 478 with conventional monopolar electrosurgery and clamp, cut and tie techniques. Compared with conventional techniques, Harmonic devices reduced total reported costs by 10% (p = 0.007), resulting in a $229 US dollars (USD) absolute reduction from mean baseline costs. Results remained relatively robust to additional sensitivity analyses. CONCLUSIONS: This systematic review and meta-analysis demonstrates that the Harmonic family of surgical devices is associated with a reduction in total reported costs in thyroidectomy compared with conventional techniques. A large portion of the overall savings derives from a reduction in operative costs. PMID- 26999564 TI - Impact attenuation of protective boxing and taekwondo headgear. AB - This study aimed to compare the impact attenuation performance of boxing and taekwondo headgear in terms of peak linear and rotational acceleration. To measure the impact attenuation of headgear, a standardized (American Society for Testing and Materials (ASTM) F-2397) martial arts headgear striker was used to impart impacts to a 50th Percentile Male Hybrid III Crash Test Dummy head and neck complex. Two boxing (Adidas and Greenhill) and two taekwondo (Adidas and Nike) headgear, approved by the Association Internationale de Boxe Amateur and the World Taekwondo Federation (WTF), were selected. Each of the selected headgear was fitted to the Hybrid III head and subsequently subjected to five impacts at the front and side with a maximum impact interim time of 60 seconds by the rotating striker at 8 +/- 0.3 m/s. Linear and rotational acceleration were recorded at 10,000 Hz. There were significant interactions of the impact location and brand on the rotational acceleration, F(3,40) = 6.7, p < .05. There were significant main effects of both impact location F(1,40) = 9.07, p < .05 and headgear brand F(3,40) = 9.9, p < .05 on the linear acceleration. Pairwise comparisons show significant differences between the front and side for both linear and rotational acceleration. The headgear tested failed the ASTM high impact test requirement to reduce the linear acceleration to below a threshold of 150 g. Further development of headgear to reduce impact linear and rotational acceleration magnitudes should be called for by the relevant sport governing bodies and initiated by headgear manufactures. PMID- 26999565 TI - Low-Flow Vascular Malformation Pitfalls: From Clinical Examination to Practical Imaging Evaluation--Part 1, Lymphatic Malformation Mimickers. AB - OBJECTIVE: Palpable subcutaneous masses present in various shapes and sizes in the pediatric population and, accordingly, represent a variety of underlying causes. Lymphatic and venous malformations are among the most common pediatric subcutaneous lesions. However, there are congenital and acquired, as well as benign and malignant, soft-tissue masses that can mimic them clinically and at imaging. CONCLUSION: Here, we review the natural history, wide range of clinical presentations, and varied but characteristic imaging appearance of lymphatic malformations that can pose diagnostic difficulties in children. In addition, the clinical and imaging characteristics of some pediatric soft-tissue pathologies that can mimic lymphatic malformations and clues to reach a proper diagnosis are highlighted. PMID- 26999567 TI - Reflex epileptic mechanisms in ictogenesis and therapeutic consequences. AB - Recent studies of reflex epileptic mechanisms in human epilepsy using advanced methods of neurophysiology and functional neuroimaging have contributed much to elucidate pathophysiological processes of seizure generation. Whereas in lesional focal epilepsies reflex mechanisms usually relate directly to the anatomical focus, in system epilepsies they have helped to define which functional anatomical systems serving physiological function are recruited by the ictogenic mechanisms. Reflex epileptic seizures can often be prevented by avoidance or modification of triggers or by prophylactic benzodiazepine administration. Surgical options apply to focal cases. According to restricted experiences with pharmacotherapy, without controlled studies and little information on new AEDs, reflex seizures in system epilepsies appear to respond best to valproic acid and in focal epilepsies, to carbamazepine. PMID- 26999566 TI - Elevated high-sensitivity troponin T levels are associated with adverse cardiac remodelling and myocardial fibrosis in hypertrophic cardiomyopathy. AB - INTRODUCTION: Clinical manifestations of hypertrophic cardiomyopathy (HCM) range from asymptomatic disease to early-onset heart failure and sudden cardiac death (SCD). Risk stratification for SCD remains imperfect and novel risk markers are needed. The aim of our study was to evaluate the association of elevated high sensitivity cardiac troponin T levels (hs-cTnT) with the severity of disease expression and adverse events in patients with HCM. METHODS: All patients followed-up at a dedicated HCM clinic at a tertiary care centre between April 2012 and March 2014 were analysed. The clinical care track for these patients includes 12-lead ECG, blood work-up, echocardiography, Holter ECG, exercise stress testing and cardiovascular magnetic resonance imaging (CMR). Clinical data were obtained from medical records. RESULTS: Of 91 HCM patients (77% males, mean age at follow up 51 +/- 16 years), 46 (51%) had elevated hs-cTnT levels (>0.014 ng/ml). Patients with elevated hs-cTnT levels had greater maximum wall thickness (23 +/- 7 mm vs 19 +/- 3 mm, p = 0.001), more often had myocardial fibrosis (96% vs 54%, p <0.001), and lower exercise capacity (90% predicted vs 76% predicted, p = 0.002). There was a trend towards lower event-free survival estimates (Kaplan Meier method, 15% vs 7%, p = 0.16). CONCLUSIONS: Elevated hs-cTnT levels in HCM patients are associated with disease severity and, potentially, with more adverse cardiac events. Future studies should test whether integration of hs-cTnT in clinical decision algorithms will improve risk stratification. PMID- 26999568 TI - The clinical management of inoperable endometrial carcinoma. AB - Unresectable endometrial cancer, while rare, has a very poor prognosis, with a survival rate of 2 to 8 months. Although endometrial cancer is generally regarded as a survivable disease, the less common advanced and aggressive forms account for a large portion of endometrial cancer related deaths. Given the paucity of inoperable disease, randomized clinical data is lacking in this specific patient population. Management decisions regarding radiation therapy or systemic therapy are largely guided by the existing data in the setting of recurrence or second line treatment, adjuvant therapy following optimal debulking, or in patients who are considered inoperable due to medical comorbidities rather than the extent of their disease. PMID- 26999569 TI - Biological fractionation of stable Ca isotopes in Gottingen minipigs as a physiological model for Ca homeostasis in humans. AB - In order to investigate fractionation of calcium (Ca) isotopes in vertebrates as a diagnostic tool to detect Ca metabolism dysfunction we analyzed the Ca isotopic composition (delta(44/40)Ca = [((44)Ca/(40)Ca)sample/((44)Ca/(40)Ca)reference]-1) of diet, faeces, blood, bones and urine from Gottingen minipigs, an animal model for human physiology. Samples of three groups were investigated: 1. control group (Con), 2. group with glucocorticosteroid induced osteoporosis (GIO) and 3. group with Ca and vitamin D deficiency induced osteomalacia (-CaD). In contrast to Con and GIO whose average delta(44/40)Cafaeces values (0.39 +/- 0.130/00 and 0.28 +/- 0.080/00, respectively) tend to be lower than their diet (0.47 +/- 0.020/00), delta(44/40)Cafaeces of -CaD (-0.27 +/- 0.210/00) was significantly lower than their delta(44/40)Cadiet (0.37 +/- 0.030/00), but also lower than delta(44/40)Cafaeces of Con and GIO. We suggest that the low delta(44/40)Cafaeces of -CaD might be due to the contribution of isotopically light Ca from gastrointestinal fluids during gut passage. Assuming that this endogenous Ca source is a common physiologic feature, a fractionation during Ca absorption is also required for explaining delta(44/40)Cafaeces of Con and GIO. The delta(44/40)Caurine of all groups are high (>2.00/00) reflecting preferential renal reabsorption of light Ca isotopes. In Gottingen minipigs we found a Ca isotope fractionation between blood and bones (Delta(44/40)Cablood-bone) of 0.68 +/- 0.150/00. PMID- 26999570 TI - Usefulness of monocyte to HDL-cholesterol ratio to predict high SYNTAX score in patients with stable coronary artery disease. AB - AIM: We aimed to investigate whether baseline monocyte to high-density lipoprotein cholesterol ratio (MHR), an easily available inflammatory and oxidative stress marker, is associated with SYNTAX score. PATIENTS & METHODS: In this cross-sectional study, n = 1229 consecutive patients with coronary artery disease were classified into two groups, low SYNTAX score (<=22) and high SYNTAX score (>=23). RESULTS: MHRs were significantly higher in patients with high SYNTAX score (p < 0.05). In multivariate regression analysis, MHR remained as independent predictor of high SYNTAX score together with C-reactive protein (CRP), hypertension and diabetes mellitus. In correlation analysis, MHR showed significant positive correlations with SYNTAX score (r = 0.371, p < 0.001) and CRP level (r = 0.336, p < 0.001). CONCLUSION: This study suggests MHR is independently associated with burden of coronary atherosclerosis. PMID- 26999572 TI - Response to ibrutinib of refractory life-threatening autoimmune hemolytic anemia occurring in a relapsed chronic lymphocytic leukemia patient with 17p deletion. PMID- 26999571 TI - Efficient Synthesis of Nicotinamide-1-15N for Ultrafast NMR Hyperpolarization Using Parahydrogen. AB - Nicotinamide (a vitamin B3 amide) is one of the key vitamins as well as a drug for treatment of M. tuberculosis, HIV, cancer, and other diseases. Here, an improved Zincke reaction methodology is presented allowing for straightforward and scalable synthesis of nicotinamide-1-(15)N with an excellent isotopic purity (98%) and good yield (55%). (15)N nuclear spin label in nicotinamide-1-(15)N can be NMR hyperpolarized in seconds using parahydrogen gas. NMR hyperpolarization using the process of temporary conjugation between parahydrogen and to-be hyperpolarized biomolecule on hexacoordinate iridium complex via the Signal Amplification By Reversible Exchange (SABRE) method significantly increases detection sensitivity (e.g., >20,000-fold for nicotinamide-1-(15)N at 9.4 T) as has been shown by Theis T. et al. (J. Am. Chem. Soc. 2015, 137, 1404), and hyperpolarized in this fashion, nicotinamide-1-(15)N can be potentially used to probe metabolic processes in vivo in future studies. Moreover, the presented synthetic methodology utilizes mild reaction conditions, and therefore can also be potentially applied to synthesis of a wide range of (15)N-enriched N heterocycles that can be used as hyperpolarized contrast agents for future in vivo molecular imaging studies. PMID- 26999573 TI - Mortality from laparoscopic antireflux surgery in a nationwide cohort of the working-age population. AB - BACKGROUND: Both medication and surgery are effective treatments for severe gastro-oesophageal reflux disease (GORD). Postoperative risks have contributed to decreased use of antireflux surgery. The aim of this study was to assess short term mortality following primary laparoscopic fundoplication. METHODS: This was a population-based nationwide cohort study including all Swedish hospitals that performed laparoscopic fundoplication between 1997 and 2013. All patients aged 18 65 years with GORD who underwent primary laparoscopic fundoplication during the study interval were included. The primary outcome was absolute all-cause and surgery-related 90- and 30-day mortality. Secondary outcomes were reoperation and length of hospital stay. Logistic regression was used to calculate odds ratios with 95 per cent confidence intervals of reoperation within 90 days and prolonged hospital stay (4 days or more). RESULTS: Of 8947 included patients, 5306 (59.3 per cent) were men and 551 (6.2 per cent) had significant co-morbidity (Charlson score above 0). Median age at surgery was 48 years, and median hospital stay was 2 days. The annual rate of laparoscopic fundoplication decreased from 15.3 to 2.4 patients per 100 000 population during the study period, whereas the proportion of patients with co-morbidity increased more than twofold. All-cause 90- and 30 day mortality rates were 0.08 per cent (7 patients) and 0.03 per cent (3 patients) respectively. Only one death (0.01 per cent) was directly surgery related. The 90-day reoperation rate was 0.4 per cent (39 patients). Co-morbidity and older age were associated with an increased risk of prolonged hospital stay, but not reoperation. CONCLUSION: This population-based study revealed very low mortality and reoperation rates following primary laparoscopic fundoplication in the working-age population. The findings may influence clinical decision-making in the treatment of severe GORD. PMID- 26999574 TI - [Ru(bpy)2(7-CH3-dppz)](2+) and [Ru(phen)2(7-CH3-dppz)](2+) as metallointercalators that affect third-strand stabilization of the poly(U)poly(A)*poly(U) triplex. AB - Stable RNA triplexes play key roles in many biological processes. However, due to Hoogsteen base pairing, triplexes are thermodynamically less stable than the corresponding duplexes. To understand the factors effecting the stabilization of RNA triplexes by octahedral ruthenium(ii) complexes, two Ru(ii) complexes, [Ru(bpy)2(7-CH3-dppz)](2+) (Ru) and [Ru(phen)2(7-CH3-dppz)](2+) (Ru), have been synthesized and characterized in this work. The interactions of the two Ru(ii) complexes with the poly(U)poly(A)*poly(U) triplex are investigated by spectrophotometry, spectrofluorometry, circular dichroism as well as viscometry. The results demonstrate that the two complexes are able to enhance the stability of the RNA triplex and serve as molecular "light switches" for the triplex. However, Ru and Ru affecting the stabilization of the third strand are significantly weaker than that of the Watson-Crick base-paired duplex, suggesting that the binding of the two complexes with the triplex is favored by the Watson Crick base-paired duplex to a large extent. In addition, considering the nature of Ru and Ru, we presume that their binding differences may be due to different ancillary ligand effects. This study further advances our knowledge on the interaction of RNA triple-stranded structures with metal complexes, particularly with Ru(ii) complexes. PMID- 26999575 TI - Formate-derived H2 , a driver of hydrogenotrophic processes in the root-zone of a methane-emitting fen. AB - Wetlands are important sources of globally emitted methane. Plants mediate much of that emission by releasing root-derived organic carbon, including formate, a direct precursor of methane. Thus, the objective of this study was to resolve formate-driven processes potentially linked to methanogenesis in the fen root zone. Although, formate was anticipated to directly trigger methanogenesis, the rapid anaerobic consumption of formate by Carex roots unexpectedly yielded H2 and CO2 via enzymes such as formate-H2 -lyase (FHL), and likewise appeared to enhance the utilization of organic carbon. Collectively, 57 [FeFe]- and [NiFe] hydrogenase-containing family level phylotypes potentially linked to FHL activity were detected. Under anoxic conditions, root-derived fermentative Citrobacter and Hafnia isolates produced H2 from formate via FHL. Formate-derived H2 fueled methanogenesis and acetogenesis, and methanogenic (Methanoregula, Methanobacterium, Methanocella) and acetogenic (Acetonema, Clostridum, Sporomusa) genera potentially linked to these hydrogenotrophic activities were identified. The findings (i) provide novel insights on highly diverse root-associated FHL containing taxa that can augment secondary hydrogenotrophic processes via the production of formate-derived H2 , (ii) demonstrate that formate can have a 'priming' effect on the utilization of organic carbon, and (iii) raise questions regarding the fate of formate-derived H2 when it diffuses away from the root zone. PMID- 26999576 TI - Turning On and Off Photoinduced Electron Transfer in Fluorescent Proteins by pi Stacking, Halide Binding, and Tyr145 Mutations. AB - Photoinduced electron transfer in fluorescent proteins from the GFP family can be regarded either as an asset facilitating new applications or as a nuisance leading to the loss of optical output. Photooxidation commonly results in green to-red photoconversion called oxidative redding. We discovered that yellow FPs do not undergo redding; however, the redding is restored upon halide binding. Calculations of the energetics of one-electron oxidation and possible electron transfer (ET) pathways suggested that excited-state ET proceeds through a hopping mechanism via Tyr145. In YFPs, the pi-stacking of the chromophore with Tyr203 reduces its electron-donating ability, which can be restored by halide binding. Point mutations confirmed that Tyr145 is a key residue controlling ET. Substitution of Tyr145 by less-efficient electron acceptors resulted in highly photostable mutants. This strategy (i.e., calculation and disruption of ET pathways by mutations) may represent a new approach toward enhancing photostability of FPs. PMID- 26999577 TI - Temporal Trends and Geographic Variations in Dementia Mortality in China Between 2006 and 2012: Multilevel Evidence From a Nationally Representative Sample. AB - OBJECTIVES: We aimed to explore the temporal trends and geographic variations in dementia mortality in China. MATERIALS AND METHODS: Annual dementia mortality counts (years 2006 to 2012) in 161 counties and districts (Disease Surveillance Points, DSP) were extracted from the nationally representative China Mortality Surveillance System and stratified by 5-year age group (aged >65), sex, and time. These counts were linked to annually adjusted denominator populations. Multilevel negative binomial regression with random intercepts and slopes were used to investigate spatiotemporal variation in dementia mortality. RESULTS: Dementia mortality varied over 2-fold between DSPs (median rate ratio: 2.59). Significant variation in DSP slopes through time (variance 0.075, SE 0.020) indicated spatiotemporal variations. Mortality rates were significantly higher in the east (rate ratio 2.28; 95% confidence intervals, 1.45-3.60) compared with the north. There was a declining trend in 2 (east and northwest) of the 7 regions. Dementia mortality decreased by 15% in urban areas but increased by 24% in rural areas. CONCLUSIONS: Our findings indicate that regional inequalities in dementia mortality are salient, and the increase in mortality rates in rural areas is an emerging public health challenge in China. Tailored preventive health strategies should be in place to narrow down this avoidable and wholly unnecessary inequality. PMID- 26999578 TI - Impact of a Reading Priority Scoring System on the Prioritization of Examination Interpretations. AB - OBJECTIVE: Our institution implemented a read priority scoring system to combat the known limitations of traditional methods for the prioritization of examination interpretations by radiologists. We aimed to determine the impact on report turnaround time (RTAT) and RTAT variability. MATERIALS AND METHODS: On examination completion, technologists entered a read priority score (1-9) using provided definitions. We retrospectively reviewed the median RTAT and RTAT variability (i.e., interquartile range length) for radiology examinations (n = 615,541; 2011-2014). We used Spearman correlation coefficients to determine the relationships between read priority scores and the median RTAT and the RTAT variability by year. We compared median RTAT and RTAT variability between early (2011) versus late (2012-2014) adoption phases using distribution-free random permutation tests. RESULTS: Ranked correlations showed yearly improvement, leading to a near-perfect ranking of median RTAT (r = 0.98, p < 0.001) and a perfect ranking of RTAT variability (r = 1.00, p < 0.001) by nine levels of priority. Eight of the nine priority levels showed a reduction in median RTAT between the early and late phases, and the three most urgent levels--that is, 1, 2, and 3--improved by 23%, 5%, and 70% (all, p < 0.001), respectively. Only one priority level (4, defined as outpatient urgent [8% of studies]) showed significant worsening by 15% (p < 0.001). The three most urgent levels of priority also showed improvements in RTAT variability (61%, 17%, 71%, respectively; all, p < 0.01). Only the lowest level of priority (9) exhibited a significant worsening in RTAT variability by 9% (p < 0.01). CONCLUSION: A reading priority scoring system with defined clinical scenarios yielded desirable prioritization of examination interpretations by radiologists as evidenced by appropriate and improved stratification of RTATs and RTAT variability. PMID- 26999579 TI - Complementary Metal-Oxide-Semiconductor Integrated Carbon Nanotube Arrays: Toward Wide-Bandwidth Single-Molecule Sensing Systems. AB - There is strong interest in realizing genomic molecular diagnostic platforms that are label-free, electronic, and single-molecule. One attractive transducer for such efforts is the single-molecule field-effect transistor (smFET), capable of detecting a single electronic charge and realized with a point-functionalized exposed-gate one-dimensional carbon nanotube field-effect device. In this work, smFETs are integrated directly onto a custom complementary metal-oxide semiconductor chip, which results in an array of up to 6000 devices delivering a measurement bandwidth of 1 MHz. In a first exploitation of these high-bandwidth measurement capabilities, point functionalization through electrochemical oxidation of the devices is observed with microsecond temporal resolution, which reveals complex reaction pathways with resolvable scattering signatures. High rate random telegraph noise is detected in certain oxidized devices, further illustrating the measurement capabilities of the platform. PMID- 26999581 TI - Flexible, Freestanding, and Binder-free SnO(x)-ZnO/Carbon Nanofiber Composites for Lithium Ion Battery Anodes. AB - Here, we demonstrate the production of electrospun SnO(x)-ZnO polyacrylonitrile (PAN) nanofibers (NFs) that are flexible, freestanding, and binder-free. This NF fabric is flexible and thus can be readily tailored into a coin for further cell fabrication. These properties allow volume expansion of the oxide materials and provide shortened diffusion pathways for Li ions than those achieved using the nanoparticle approach. Amorphous SnO(x)-ZnO particles were uniformly dispersed in the carbon NF (CNF). The SnO(x)-ZnO CNFs with a Sn:Zn ratio of 3:1 exhibited a superior reversible capacity of 963 mA.h.g(-1) after 55 cycles at a current density of 100 mA.g(-1), which is three times higher than the capacity of graphite-based anodes. The amorphous NFs facilitated Li2O decomposition, thereby enhancing the reversible capacity. ZnO prevented the aggregation of Sn, which, in turn, conferred stable and high discharge capacity to the cell. Overall, the SnO(x)-ZnO CNFs were shown to exhibit remarkably high capacity retention and high reversible and rate capacities as Li ion battery anodes. PMID- 26999580 TI - EGF-coated gold nanoparticles provide an efficient nano-scale delivery system for the molecular radiotherapy of EGFR-positive cancer. AB - Purpose Radiolabeled antibodies and peptides hold promise for molecular radiotherapy but are often limited by a low payload resulting in inadequate delivery of radioactivity to tumour tissue and, therefore, modest therapeutic effect. We developed a facile synthetic method of radiolabeling indium-111 (111In) to epidermal growth factor (EGF)-gold nanoparticles (111In-EGF-Au NP) with a high payload. Materials and methods EGF-Au NP were prepared via an interaction between gold and the disulphide bonds of EGF and radiolabeled using 111InCl3. Targeting efficiency was investigated by quantitating internalized radioactivity and by confocal imaging following exposure of MDA-MB-468 (1.3 * 106 EGFR/cell) and MCF-7 (104 EGFR/cell) cells to Cy3-EGF-Au NP. Cytotoxicity was evaluated in clonogenic assays. Results The proportion of total administered radioactivity that was internalized by MDA-MB-468 and MCF-7 cells was 15% and 1.3%, respectively (mixing ratio of EGF:Au of 160). This differential uptake in the two cell lines was confirmed using confocal microscopy. 111In-EGF-Au NP were significantly more radiotoxic to MDA-MB-468 than MCF-7 cells with a surviving fraction of 17.1 +/- 4.4% versus 89.8 +/- 1.4% (p < 0.001) after exposure for 4 h. Conclusions An 111In-labeled EGF-Au nanosystem was developed. It enabled targeted delivery of a high 111In payload specifically to EGFR-positive cancer cells leading to radiotoxicity that can be exploited for molecularly targeted radiotherapy. PMID- 26999582 TI - Reaching Adolescents for Prevention: The Role of Pediatric Emergency Department Health Promotion Advocates. AB - OBJECTIVES: Almost 200,000 adolescents visit US emergency departments (EDs) yearly for conditions involving underage drinking but receive no follow-up referral. Other health risk behaviors resulting in sexually transmitted infections, car crashes, and assault-related injury are common among adolescents. A pediatric ED (PED) visit presents an opportunity to discuss and promote prevention. We report here on implementation of a new PED navigator/extender role, the Health Promotion Advocate (HPA). METHODS: Health Promotion Advocates surveyed patients to identify health risks, stresses, and needs. A positive screen triggered a brief conversation containing the following elements: permission to discuss risks/needs; exploration of context (a typical day in your life); brief feedback (information and norms); exploration of benefits and consequences of risk behaviors; assessment of readiness to change; calling up assets, instilling hope; discussing challenges of change; negotiating a menu of options and prescription for change; referrals to primary care, community resources; and treatment services as indicated. RESULTS: During 2009-2013, HPAs screened 2149 PED patients aged 14 to 21 years and referred 834 for an array of services (eg, primary care, mental health, insurance, personal safety, human immunodeficiency virus testing, general education diploma (GED), employment, housing, and food pantries) to address reported health risks; 785 screened positive for at-risk substance use (53% female, 36% without primary care). Among them, 636 received a brief intervention; 546 were referred to specialized substance abuse treatment. Two case studies are presented to illustrate the engagement and referral process. CONCLUSIONS: Health Promotion Advocates working as PED team members can extend PED services beyond the scope of the presenting complaint. PMID- 26999583 TI - Factors Associated With Poor Outcome in Childhood Swimming Pool Submersions. AB - OBJECTIVES: The aims of the study were to determine factors associated with poor outcome in childhood swimming pool submersions and to study the association of bystander resuscitation with clinical outcome. METHODS: This was a retrospective study of swimming pool submersion victims younger than 18 years in a metropolitan area from 2003 to 2007. Submersion, prehospital, and victim data were obtained from hospital, Emergency Medical Services, and fatality records. Outcome based on survival at hospital discharge was favorable (baseline/mild impairment) or poor (death/severe impairment). Logistic regression determined factors associated with poor outcome. RESULTS: There were 260 submersions. Outcomes were available for 211 (81%). The median age was 4 years; 68% were males. Most incidents occurred at single residential pools (48%) and multiresidential pools (35%). Mortality was 23%; 75% had favorable outcomes. Favorable outcomes occurred in 8.6% (3/35) of victims with absent pulse at the scene. Descriptive analyses revealed significant differences in submersions that occurred on weekdays, during the summer, submersions lasting 5 minutes or more, with on-scene apnea or cardiac arrest needing cardiopulmonary resuscitation, rescuer type, and transfer to tertiary care. Logistic regression revealed that poor outcome was significantly associated with prolonged submersions and those that occurred on a weekday. Furthermore, hospitalization reduced the odds of a poor outcome by 81% when compared with victims who were not hospitalized. Bystander resuscitation was not significantly associated with outcome. CONCLUSIONS: Childhood swimming pool submersions, which occur on weekdays and with prolonged submersion times, are associated with poor outcome. Bystander resuscitation is not significantly associated with outcome. PMID- 26999584 TI - On Shaky Ground: Learner Response and Confidence After Tabletop Earthquake Simulation. AB - OBJECTIVE: The aim of this study was to evaluate residents' confidence and attitudes related to management of earthquake victims during a tabletop simulation and 6 months after the intervention. METHODS: Pediatric residents from 4 training programs were recruited via e-mail. The tabletop simulation involved 3 pediatric patients (crush injury, head injury, and a nonverbal patient with minor injuries). A facilitated debriefing took place after the simulation. The same simulation was repeated 6 months later. A survey was administered before the simulation, immediately after, and after the 6-month repeat simulation to determine participants' self-rated confidence and willingness to respond in the event of a disaster. A 5-point Likert scale that ranged through novice, advanced beginner, competent, proficient, and expert was used. RESULTS: Ninety-nine participants completed the survey before the initial simulation session. Fifty one residents completed the immediate postsurvey, and 75 completed the 6-month postsurvey. There was a statistically significant improvement in self-rated confidence identifying and managing victims of earthquake disasters after participating in the simulation, with 3% rating themselves as competent on the presurvey and 33% rating themselves as competent on the postsurvey (P < 0.05). There was a nonstatistically significant improvement in confidence treating suspected traumatic head injury as well as willingness to deploy to both domestic and international disasters. CONCLUSIONS: Tabletop simulation can improve resident comfort level with rare events, such as caring for children in the aftermath of an earthquake. Tabletop can also be easily integrated into resident curriculum and may be an effective way to provide disaster medical response training for trainees. PMID- 26999585 TI - Epidemiology of the Critically Ill Child in the Resuscitation Bay. AB - BACKGROUND: Children account for approximately 33 million annual emergency department (ED) visits in the United States. The spectrum and frequency of children with a critical illness presenting to an ED has not been previously analyzed. OBJECTIVE: The purpose of this study was to examine the range of critical illness presenting to a tertiary Children's Hospital ED. METHODS: This study was a retrospective chart review of all pediatric patients requiring immediate care in the medical resuscitation bay during a 25-month period from August 2005 to September 2007. Data are from a single center, academic, tertiary care pediatric hospital. A log of all patients requiring immediate care is kept in the medical resuscitation bay. Patients recorded in the log for a period of 25 consecutive months were reviewed for type of critical illness, frequency of critical illness, mode of arrival, and outcome. Trauma patients were excluded. RESULTS: There were approximately 45,000 pediatric visits per year with a total of 87,766 patients seen during the study period. There were 249 pediatric patients who required care in the medical resuscitation bay during the reviewed period. Complete data were obtained from 242 subjects' charts. Patients requiring immediate care accounted for 0.28% of all the visits. CONCLUSIONS: This study documents the infrequent need for pediatric critical care in the ED of a nonacademic tertiary children's hospital in the United States and reinforces the need to provide protocols, mock codes, and simulation labs in preparation for critically ill children. PMID- 26999586 TI - The Utility of Cranial Ultrasound for Detection of Intracranial Hemorrhage in Infants. AB - OBJECTIVE: The objective of this study was to evaluate the sensitivity and specificity of cranial ultrasound (CUS) for detection of intracranial hemorrhage (ICH) in infants with open fontanels. METHODS: This was a retrospective study of infants younger than 2 years who had a CUS performed for the evaluation of potential ICH. We excluded patient with CUSs that were done for reasons related to prematurity, transplant or oncologic evaluations, routine follow-up or preoperative screen, or congenital and known perinatal anomalies. Two clinicians independently classified each of the patients with ICH into significant or insignificant based on the radiology reports. RESULTS: Of 4948 CUS studies performed during the 5-year study period, 283 studies fit the inclusion criteria. Patient age ranged from 0 to 458 days, with a median of 33 days. There were 39 total cases of ICH detected, with 27 significant bleeds and 12 insignificant bleeds. Using computed tomography, magnetic resonance imaging, or clinical outcome as criterion standard, the overall ultrasound sensitivity and specificity for bleed were 67% (confidence interval [CI], 50%-81%) and 99% (CI, 97%-100%), respectively. For those with significant bleeds, the overall sensitivity was 81% (CI, 62%-94%), and for those with insignificant bleeds, it was 33% (CI, 1%-65%). CONCLUSIONS: The sensitivity of CUS is inadequate to justify its use as a screening tool for detection of ICH in young infants. PMID- 26999587 TI - Purification-Free Method for Preparing Technetium-99m-Labeled Multivalent Probes for Enhanced in Vivo Imaging of Saturable Systems. AB - Metallic radionuclides provide target-specific radiolabeled probes for molecular imaging in radiochemical yields sufficient for administration to subjects without purification. However, unlabeled ligands in the injectate can compete for targeted molecules with radiolabeled probes, which eventually necessitates postlabeling purification. Herein we describe a "1 to 3" design to circumvent the issue by taking advantage of inherent coordination properties of technetium-99m ((99m)Tc). A monovalent RGD ligand possessing an isonitrile as a coordinating moiety (CN-RGD) was reacted with [(99m)Tc(CO)3(OH2)3](+) to prepare [(99m)Tc(CO)3(CN-RGD)3](+) in over 95% radiochemical yields. This complex exhibited higher integrin alphavbeta3 binding affinity than its unlabeled monovalent ligand, primarily due to its multivalency. This compound visualized a murine tumor without removing unlabeled ligands, while a (99m)Tc-labeled monovalent probe derived from a monovalent ligand could not. The metal coordination-mediated synthesis of radiolabeled multivalent probes thereby can be a useful approach for preparing ready-to-use target-specific probes labeled with (99m)Tc and other metallic radionuclides of interest. PMID- 26999589 TI - Benzotrithiophene versus Benzo/Naphthodithiophene Building Blocks: The Effect of Star-Shaped versus Linear Conjugation on Their Electronic Structures. AB - The synthesis, characterization, and optical properties of a novel star-shaped oligothiophene with a central rigid trithienobenzene (BTT) core and diketopyrrolopyrrole (DPP) units are reported and compared with homologous linear systems based on the benzodithiophene (BDT) and the naphthodithiophene (NDT) units end capped with DPPs. This comparison is aimed at elucidating the effect of the star-shaped configuration versus linear conformation on the optical and electrical properties. Electronic and vibrational spectroscopies, together with transient absorption spectroscopy, scanning electronic microscopy, and DFT calculations are used to understand not only the molecular properties of these semiconductors, but also to analyze the supramolecular aggregation in these derivatives. We conclude that although the subject star-shaped derivative is not optimal in terms of pi-conjugation, its extended BTT unit significantly favors intermolecular pi-stacking interactions, which is interesting for their applications in devices. Field-effect transistors and solar cells were fabricated with these new molecular semiconductors and the performance difference discussed. PMID- 26999588 TI - Validation of the 17-item Hamilton Depression Rating Scale definition of response for adults with major depressive disorder using equipercentile linking to Clinical Global Impression scale ratings: analysis of Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) data. AB - OBJECTIVE: The study aimed to define thresholds of clinically significant change in 17-item Hamilton Depression Rating Scale (HDRS-17) scores using the Clinical Global Impression-Improvement (CGI-I) Scale as a gold standard. METHODS: We conducted a secondary analysis of individual patient data from the Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study, an 8-week, single-arm clinical trial of citalopram or escitalopram treatment of adults with major depression. We used equipercentile linking to identify levels of absolute and percent change in HDRS-17 scores that equated with scores on the CGI-I at 4 and 8 weeks. Additional analyses equated changes in the HDRS-7 and Bech-6 scale scores with CGI-I scores. RESULTS: A CGI-I score of 2 (much improved) corresponded to an absolute decrease (improvement) in HDRS-17 total score of 11 points and a percent decrease of 50-57%, from baseline values. Similar results were observed for percent change in HDRS-7 and Bech-6 scores. Larger absolute (but not percent) decreases in HDRS-17 scores equated with CGI-I scores of 2 in persons with higher baseline depression severity. CONCLUSIONS: Our results support the consensus definition of response based on HDRS-17 scores (>50% decrease from baseline). A similar definition of response may apply to the HDRS-7 and Bech-6. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999590 TI - Influence of oxidative homeostasis on bacterial density and cost of infection in Drosophila-Wolbachia symbioses. AB - The evolution of symbioses along the continuum between parasitism and mutualism can be influenced by the oxidative homeostasis, that is the balance between reactive oxygen species (ROS) and antioxidant molecules. Indeed, ROS can contribute to the host immune defence to regulate symbiont populations, but are also toxic. This interplay between ROS and symbiosis is notably exemplified by recent results in arthropod-Wolbachia interactions. Wolbachia are symbiotic bacteria involved in a wide range of interactions with their arthropods hosts, from facultative, parasitic associations to obligatory, mutualistic ones. In this study, we used Drosophila-Wolbachia associations to determine whether the oxidative homeostasis plays a role in explaining the differences between phenotypically distinct arthropod-Wolbachia symbioses. We used Drosophila lines with different Wolbachia infections and measured the effects of pro-oxidant (paraquat) and antioxidant (glutathione) treatments on the Wolbachia density and the host survival. We show that experimental manipulations of the oxidative homeostasis can reduce the cost of the infection through its effect on Wolbachia density. We discuss the implication of this result from an evolutionary perspective and argue that the oxidative homeostasis could underlie the evolution of tolerance and dependence on Wolbachia. PMID- 26999591 TI - Deformability-based cell selection with downstream immunofluorescence analysis. AB - Mechanical properties of single cells have been shown to relate to cell phenotype and malignancy. However, until recently, it has been difficult to directly correlate each cell's biophysical characteristics to its molecular traits. Here, we present a cell sorting technique for use with a suspended microchannel resonator (SMR), which can measure biophysical characteristics of a single cell based on the sensor's record of its buoyant mass as well as its precise position while it traverses through a constricted microfluidic channel. The measurement provides information regarding the amount of time a cell takes to pass through a constriction (passage time), as related to the cell's deformability and surface friction, as well as the particular manner in which it passes through. In the method presented here, cells of interest are determined based on passage time, and are collected off-chip for downstream immunofluorescence imaging. The biophysical single-cell SMR measurement can then be correlated to the molecular expression of the collected cell. This proof-of-principle is demonstrated by sorting and collecting tumor cells from cell line-spiked blood samples as well as a metastatic prostate cancer patient blood sample, identifying them by their surface protein expression and relating them to distinct SMR signal trajectories. PMID- 26999592 TI - A Deep Insight into the Sialome of Male and Female Aedes aegypti Mosquitoes. AB - Only adult female mosquitoes feed on blood, while both genders take sugar meals. Accordingly, several compounds associated with blood feeding (i.e. vasodilators, anti-clotting, anti-platelets) are found only in female glands, while enzymes associated with sugar feeding or antimicrobials (such as lysozyme) are found in the glands of both sexes. We performed de novo assembly of reads from adult Aedes aegypti female and male salivary gland libraries (285 and 90 million reads, respectively). By mapping back the reads to the assembled contigs, plus mapping the reads from a publicly available Ae. aegypti library from adult whole bodies, we identified 360 transcripts (including splice variants and alleles) overexpressed tenfold or more in the glands when compared to whole bodies. Moreover, among these, 207 were overexpressed fivefold or more in female vs. male salivary glands, 85 were near equally expressed and 68 were overexpressed in male glands. We call in particular the attention to C-type lectins, angiopoietins, female-specific Antigen 5, the 9.7 kDa, 12-14 kDa, 23.5 kDa, 62/34 kDa, 4.2 kDa, proline-rich peptide, SG8, 8.7 kDa family and SGS fragments: these polypeptides are all of unknown function, but due to their overexpression in female salivary glands and putative secretory nature they are expected to affect host physiology. We have also found many transposons (some of which novel) and several endogenous viral transcripts (probably acquired by horizontal transfer) which are overexpressed in the salivary glands and may play some role in tissue-specific gene regulation or represent a mechanism of virus interference. This work contributes to a near definitive catalog of male and female salivary gland transcripts from Ae. aegypti, which will help to direct further studies aiming at the functional characterization of the many transcripts with unknown function and the understanding of their role in vector-host interaction and pathogen transmission. PMID- 26999593 TI - Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease. AB - INTRODUCTION: Insight into susceptibility mechanisms underlying Parkinson's disease (PD) would aid the understanding of disease etiology, enable target finding and benefit the development of more refined disease-modifying strategies. METHODS: We used intermittent low-dose MPTP (0.5 mg/kg/week) injections in marmosets and measured multiple behavioral and neurochemical parameters. Genetically diverse monkeys from different breeding families were selected to investigate inter- and intrafamily differences in susceptibility to MPTP treatment. RESULTS: We show that such differences exist in clinical signs, in particular nonmotor PD-related behaviors, and that they are accompanied by differences in neurotransmitter levels. In line with the contribution of a genetic component, different susceptibility phenotypes could be traced back through genealogy to individuals of the different families. CONCLUSION: Our findings show that low-dose MPTP treatment in marmosets represents a clinically relevant PD model, with a window of opportunity to examine the onset of the disease, allowing the detection of individual variability in disease susceptibility, which may be of relevance for the diagnosis and treatment of PD in humans. PMID- 26999594 TI - IL-6 Signaling in Myelomonocytic Cells Is Not Crucial for the Development of IMQ Induced Psoriasis. AB - Psoriasis is an autoimmune skin disease that is associated with aberrant activity of immune cells and keratinocytes. In mice, topical application of TLR7/8 agonist IMQ leads to a skin disorder resembling human psoriasis. Recently, it was shown that the IL-23/ IL-17 axis plays a deciding role in the pathogenesis of human psoriasis, as well as in the mouse model of IMQ-induced psoriasis-like skin disease. A consequence of IL-17A production in the skin includes increased expression and production of IL-6, resulting in the recruitment of neutrophils and other myelomonocytic cells to the site of inflammation. To further investigate and characterize the exact role of IL-6 signaling in myelomonocytic cells during experimental psoriasis, we generated mice lacking the IL-6 receptor alpha specifically in myelomonocytic cells (IL-6RalphaDeltamyel). Surprisingly, disease susceptibility of these mice was not affected in this model. Our study shows that classical IL-6 signaling in myelomonocytic cells does not play an essential role for disease development of IMQ-induced psoriasis-like skin disease. PMID- 26999596 TI - Studies on the Infection, Colonization, and Movement of Pseudomonas syringae pv. actinidiae in Kiwifruit Tissues Using a GFPuv-Labeled Strain. AB - Kiwifruit bacterial canker, an economically important disease caused by Pseudomonas syringae pv. actinidiae (Psa), has caused severe losses in all major areas of kiwifruit cultivation. Using a GFPuv-labeled strain of Psa, we monitored the invasion, colonization, and movement of the pathogen in kiwifruit twigs, leaves and veins. The pathogen can invade twigs through both wounds and natural openings; the highest number of Psa is obtained in cut tissues. We determined that, following spray inoculation, Psa-GFPuv could infect leaves and cause lesions in the presence and absence of wounds. Light and transmission electron microscopic observations showed that bacterial cells colonize both phloem and xylem vessels. Bacterial infection resulted in marked alterations of host tissues including the disintegration of organelles and degeneration of protoplasts and cell walls. Furthermore, low temperature was conducive to colonization and movement of Psa-GFPuv in kiwifruit tissues. Indeed, the pathogen migrated faster at 4 degrees C than at 16 degrees C or 25 degrees C in twigs. However, the optimum temperature for colonization and movement of Psa in leaf veins was 16 degrees C. Our results, revealing a better understanding of the Psa infection process, might contribute to develop more efficacious disease management strategies. PMID- 26999597 TI - Nisin and lysostaphin activity against preformed biofilm of Staphylococcus aureus involved in bovine mastitis. AB - AIMS: The biofilm produced by Staphylococcus aureus isolates involved in clinical or subclinical bovine mastitis and the activity of nisin and lysostaphin against the preformed biofilm produced by these strains were investigated. METHODS AND RESULTS: Eighteen strains were tested and all produced biofilm. Eight strains with distinct biofilm composition were selected for the antimicrobial activity assays. The minimal inhibitory concentration of each bacteriocin was determined against the planktonic cells and ranged from 15.6 to 500 MUg ml(-1) for nisin, and from 3.9 to 50 MUg ml(-1) , for lysostaphin. Lysostaphin treatment (0.4 MUg ml(-1) ) for 4 h caused a strong Staph. aureus 4181 biofilm detachment and death of the majority of the sessile cells, while nisin treatment (100 MUg ml(-1) ) for the same time caused only a great reduction in cell viability. Additionally, combination of both bacteriocins for 4 h resulted in significant death of the sessile cells but no biofilm detachment. CONCLUSIONS: The treatment with lysostaphin alone or in combination with nisin was effective in killing most biofilm sessile cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The action of lysostaphin, either alone or in combination with nisin, against established staphylococcal biofilm may represent an alternative to bovine mastitis control. However, the duration of the treatment should be considered for its application so that the best effectiveness can be achieved. PMID- 26999595 TI - The Phenotypic Characterization of the Human Renal Mononuclear Phagocytes Reveal a Co-Ordinated Response to Injury. AB - Mammalian tissues contain networks of mononuclear phagocytes (MPh) that sense injury and orchestrate the response to it. In mice, this is affected by distinct populations of dendritic cells (DC), monocytes and macrophages and recent studies suggest the same is true for human skin and intestine but little is known about the kidney. Here we describe the analysis of MPh populations in five human kidneys and show they are highly heterogeneous and contain discrete populations of DC, monocytes and macrophages. These include: plasmacytoid DC (CD303+) and both types of conventional DC-cDC1 (CD141+ cells) and CD2 (CD1c+ cells); classical, non-classical and intermediate monocytes; and macrophages including a novel population of CD141+ macrophages clearly distinguishable from cDC1 cells. The relative size of the MPh populations differed between kidneys: the pDC population was bi-modally distributed being less than 2% of DC in two kidneys without severe injury and over 35% in the remaining three with low grade injury in the absence of morphological evidence of inflammation. There were profound differences in the other MPh populations in kidneys with high and low numbers of pDC. Thus, cDC1 cells were abundant (55 and 52.3%) when pDC were sparse and sparse (12.8-12.5%) when pDC were abundant, whereas the proportions of cDC2 cells and classical monocytes increased slightly in pDC high kidneys. We conclude that MPh are highly heterogeneous in human kidneys and that pDC infiltration indicative of low-grade injury does not occur in isolation but is part of a co ordinated response affecting all renal DC, monocyte and macrophage populations. PMID- 26999598 TI - Influenza leaves a TRAIL to pulmonary edema. AB - Influenza infection can cause acute respiratory distress syndrome (ARDS), leading to poor disease outcome with high mortality. One of the driving features in the pathogenesis of ARDS is the accumulation of fluid in the alveoli, which causes severe pulmonary edema and impaired oxygen uptake. In this issue of the JCI, Peteranderl and colleagues define a paracrine communication between macrophages and type II alveolar epithelial cells during influenza infection where IFNalpha induces macrophage secretion of TRAIL that causes endocytosis of Na,K-ATPase by the alveolar epithelium. This reduction of Na,K-ATPase expression decreases alveolar fluid clearance, which in turn leads to pulmonary edema. Inhibition of the TRAIL signaling pathway has been shown to improve lung injury after influenza infection, and future studies will be needed to determine if blocking this pathway is a viable option in the treatment of ARDS. PMID- 26999599 TI - Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. AB - Influenza A viruses (IAV) can cause lung injury and acute respiratory distress syndrome (ARDS), which is characterized by accumulation of excessive fluid (edema) in the alveolar airspaces and leads to hypoxemia and death if not corrected. Clearance of excess edema fluid is driven mostly by the alveolar epithelial Na,K-ATPase and is crucial for survival of patients with ARDS. We therefore investigated whether IAV infection alters Na,K-ATPase expression and function in alveolar epithelial cells (AECs) and the ability of the lung to clear edema. IAV infection reduced Na,K-ATPase in the plasma membrane of human and murine AECs and in distal lung epithelium of infected mice. Moreover, induced Na,K-ATPase improved alveolar fluid clearance (AFC) in IAV-infected mice. We identified a paracrine cell communication network between infected and noninfected AECs and alveolar macrophages that leads to decreased alveolar epithelial Na,K-ATPase function and plasma membrane abundance and inhibition of AFC. We determined that the IAV-induced reduction of Na,K-ATPase is mediated by a host signaling pathway that involves epithelial type I IFN and an IFN-dependent elevation of macrophage TNF-related apoptosis-inducing ligand (TRAIL). Our data reveal that interruption of this cellular crosstalk improves edema resolution, which is of biologic and clinical importance to patients with IAV-induced lung injury. PMID- 26999601 TI - Cancer's got nerve: Schwann cells drive perineural invasion. AB - The invasion of cancer cells around and into nerves is associated with increased cancer aggression and poor patient outcome. As this perineural invasion increases disease severity, a better understanding of how the process is regulated may help in the development of therapeutics to target neuronal involvement in cancer. In this issue of the JCI, Deborde and colleagues show that direct contact between Schwann cells and cancer cells promotes cancer cell dissociation, migration, and invasion. Moreover, their data specifically suggest NCAM1 as an important molecular mediator of this Schwann cell-directed regulation of cancer cells in perineural invasion. The results of this study provide new insight into the cellular and molecular mechanisms of perineural invasion. PMID- 26999600 TI - Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. AB - Adoptive immunotherapy with regulatory T cells (Tregs) is a promising treatment for allograft rejection and graft-versus-host disease (GVHD). Emerging data indicate that, compared with polyclonal Tregs, disease-relevant antigen-specific Tregs may have numerous advantages, such as a need for fewer cells and reduced risk of nonspecific immune suppression. Current methods to generate alloantigen specific Tregs rely on expansion with allogeneic antigen-presenting cells, which requires access to donor and recipient cells and multiple MHC mismatches. The successful use of chimeric antigen receptors (CARs) for the generation of antigen specific effector T cells suggests that a similar approach could be used to generate alloantigen-specific Tregs. Here, we have described the creation of an HLA-A2-specific CAR (A2-CAR) and its application in the generation of alloantigen specific human Tregs. In vitro, A2-CAR-expressing Tregs maintained their expected phenotype and suppressive function before, during, and after A2-CAR-mediated stimulation. In mouse models, human A2-CAR-expressing Tregs were superior to Tregs expressing an irrelevant CAR at preventing xenogeneic GVHD caused by HLA A2+ T cells. Together, our results demonstrate that use of CAR technology to generate potent, functional, and stable alloantigen-specific human Tregs markedly enhances their therapeutic potential in transplantation and sets the stage for using this approach for making antigen-specific Tregs for therapy of multiple diseases. PMID- 26999602 TI - Welcome to the splice age: antisense oligonucleotide-mediated exon skipping gains wider applicability. AB - Exon skipping uses antisense oligonucleotides (ASOs) to alter transcript splicing for the purpose of rescuing or modulating protein expression. In this issue of the JCI, Lee and colleagues developed and evaluated an ASO-dependent method for treating certain molecularly defined diseases associated with alterations in lamin A/C (LMNA) splicing. Exon skipping by ASOs is gaining traction as a therapeutic strategy, and the use of ASOs is now being applied to bypass mutations and generate modified but functional proteins for an array of genetic disorders. PMID- 26999603 TI - UTX demethylase activity is required for satellite cell-mediated muscle regeneration. AB - The X chromosome-encoded histone demethylase UTX (also known as KDM6A) mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish transcriptionally permissive chromatin. Loss of UTX in female mice is embryonic lethal. Unexpectedly, male UTX-null mice escape embryonic lethality due to expression of UTY, a paralog that lacks H3K27 demethylase activity, suggesting an enzyme-independent role for UTX in development and thereby challenging the need for active H3K27 demethylation in vivo. However, the requirement for active H3K27 demethylation in stem cell-mediated tissue regeneration remains untested. Here, we employed an inducible mouse KO that specifically ablates Utx in satellite cells (SCs) and demonstrated that active H3K27 demethylation is necessary for muscle regeneration. Loss of UTX in SCs blocked myofiber regeneration in both male and female mice. Furthermore, we demonstrated that UTX mediates muscle regeneration through its H3K27 demethylase activity, as loss of demethylase activity either by chemical inhibition or knock-in of demethylase dead UTX resulted in defective muscle repair. Mechanistically, dissection of the muscle regenerative process revealed that the demethylase activity of UTX is required for expression of the transcription factor myogenin, which in turn drives differentiation of muscle progenitors. Thus, we have identified a critical role for the enzymatic activity of UTX in activating muscle-specific gene expression during myofiber regeneration and have revealed a physiological role for active H3K27 demethylation in vivo. PMID- 26999604 TI - Modulation of LMNA splicing as a strategy to treat prelamin A diseases. AB - The alternatively spliced products of LMNA, lamin C and prelamin A (the precursor to lamin A), are produced in similar amounts in most tissues and have largely redundant functions. This redundancy suggests that diseases, such as Hutchinson Gilford progeria syndrome (HGPS), that are caused by prelamin A-specific mutations could be treated by shifting the output of LMNA more toward lamin C. Here, we investigated mechanisms that regulate LMNA mRNA alternative splicing and assessed the feasibility of reducing prelamin A expression in vivo. We identified an exon 11 antisense oligonucleotide (ASO) that increased lamin C production at the expense of prelamin A when transfected into mouse and human fibroblasts. The same ASO also reduced the expression of progerin, the mutant prelamin A protein in HGPS, in fibroblasts derived from patients with HGPS. Mechanistic studies revealed that the exon 11 sequences contain binding sites for serine/arginine rich splicing factor 2 (SRSF2), and SRSF2 knockdown lowered lamin A production in cells and in murine tissues. Moreover, administration of the exon 11 ASO reduced lamin A expression in wild-type mice and progerin expression in an HGPS mouse model. Together, these studies identify ASO-mediated reduction of prelamin A as a potential strategy to treat prelamin A-specific diseases. PMID- 26999605 TI - Estrogen-mediated downregulation of AIRE influences sexual dimorphism in autoimmune diseases. AB - Autoimmune diseases affect 5% to 8% of the population, and females are more susceptible to these diseases than males. Here, we analyzed human thymic transcriptome and revealed sex-associated differences in the expression of tissue specific antigens that are controlled by the autoimmune regulator (AIRE), a key factor in central tolerance. We hypothesized that the level of AIRE is linked to sexual dimorphism susceptibility to autoimmune diseases. In human and mouse thymus, females expressed less AIRE (mRNA and protein) than males after puberty. These results were confirmed in purified murine thymic epithelial cells (TECs). We also demonstrated that AIRE expression is related to sexual hormones, as male castration decreased AIRE thymic expression and estrogen receptor alpha-deficient mice did not show a sex disparity for AIRE expression. Moreover, estrogen treatment resulted in downregulation of AIRE expression in cultured human TECs, human thymic tissue grafted to immunodeficient mice, and murine fetal thymus organ cultures. AIRE levels in human thymus grafted in immunodeficient mice depended upon the sex of the recipient. Estrogen also upregulated the number of methylated CpG sites in the AIRE promoter. Together, our results indicate that in females, estrogen induces epigenetic changes in the AIRE gene, leading to reduced AIRE expression under a threshold that increases female susceptibility to autoimmune diseases. PMID- 26999606 TI - Estrogen turns down "the AIRE". AB - Genetic alterations are known drivers of autoimmune disease; however, there is a much higher incidence of autoimmunity in women, implicating sex-specific factors in disease development. The autoimmune regulator (AIRE) gene contributes to the maintenance of central tolerance, and complete loss of AIRE function results in the development of autoimmune polyendocrinopathy syndrome type 1. In this issue of the JCI, Dragin and colleagues demonstrate that AIRE expression is downregulated in females as the result of estrogen-mediated alterations at the AIRE promoter. The association between estrogen and reduction of AIRE may at least partially account for the elevated incidence of autoimmune disease in women and has potential implications for sex hormone therapy. PMID- 26999607 TI - Schwann cells induce cancer cell dispersion and invasion. AB - Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression. PMID- 26999608 TI - Driving allotolerance: CAR-expressing Tregs for tolerance induction in organ and stem cell transplantation. AB - Regulatory T cells (Tregs) modulate the function of a variety of immune cells and are critical for maintaining self-tolerance and preventing the development of autoimmune disease. Due to their ability to suppress effector T cells, Tregs have been increasingly explored for clinical use to suppress alloresponses. While this approach has been promising in preclinical models and early clinical trials, widespread clinical use of Tregs has been limited by the low number of these cells in the periphery and the unknown frequency of allo-responsive Tregs. In this issue of the JCI, MacDonald and colleagues transduced human Tregs with a chimeric antigen receptor (CAR) that targets the HLA class I molecule A2. These CAR-expressing T cells were readily activated via CAR stimulation and exerted potent immunosuppressive effects when stimulated in vitro. In a murine model of hematopoietic stem cell transplantation, CAR-modified Tregs were more effective in preventing the development of graft-versus-host disease compared with polyclonal Tregs. The results of this study lay the groundwork for the further evaluation of CAR-expressing Tregs in the prevention or treatment of transplant complications. PMID- 26999609 TI - UTX in muscle regeneration--the right dose and the right time. AB - Precise epigenetic modifications in stem cells control developmental programs and cell fate decisions. In particular, the addition or removal of trimethylation of histone 3 lysine 27 (H3K27me3) at lineage-specific genes has been linked to the repression of gene expression, and a precise balance of methyltransferases and demethylases within cells determines H3K27me3 levels. The demethylase UTX is essential for development and tissue homeostasis; however, a role for UTX in stem cell-mediated tissue regeneration is unknown. In this issue of the JCI, Dilworth and colleagues reveal that UTX and its demethylase activity are required in the muscle stem cell lineage for muscle regeneration in response to injury. Specifically, UTX mediates the removal of H3K27me3 in the promoter of the transcription factor myogenin, which regulates myogenic differentiation. The results of this study provide important insight into the contribution of epigenetic regulation in stem cell-mediated regeneration of adult tissues. PMID- 26999611 TI - Motif mimetic of epsin perturbs tumor growth and metastasis. PMID- 26999610 TI - CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability. AB - Lymphatic collecting vessels direct lymph into and from lymph nodes (LNs) and can become hyperpermeable as the result of a previous infection. Enhanced permeability has been implicated in compromised immunity due to reduced flow of lymph and immune cells to LNs, which are the primary site of antigen presentation to T cells. Presently, very little is known about the molecular signals that affect lymphatic collecting vessel permeability. Here, we have shown that lymphatic collecting vessel permeability is controlled by CCR7 and that the chronic hyperpermeability of collecting vessels observed in Ccr7-/- mice is followed by vessel fibrosis. Reexpression of CCR7 in DCs, however, was sufficient to reverse the development of such fibrosis. IFN regulatory factor 4-positive (IRF4+) DCs constitutively interacted with collecting lymphatics, and selective ablation of this DC subset in Cd11c-Cre Irf4fl/fl mice also rendered lymphatic collecting vessels hyperpermeable and fibrotic. Together, our data reveal that CCR7 plays multifaceted roles in regulating collecting vessel permeability and fibrosis, with one of the key players being IRF4-dependent DCs. PMID- 26999612 TI - Comparing the Curative Effects between Femtosecond Laser-Assisted Cataract Surgery and Conventional Phacoemulsification Surgery: A Meta-Analysis. AB - PURPOSE: To compare the outcomes of femtosecond laser-assisted cataract surgery (FLACS) with those of conventional phacoemulsification surgery (CPS) for age related cataracts. METHODS: A comprehensive literature search of PubMed, EMBASE, and the Cochrane Controlled Trials Register was conducted to identify randomized controlled trials (RCT) and comparative cohort studies comparing FLACS with CPS. Endothelial cell loss percentage (ECL%), central corneal thickness (CCT), corrected and uncorrected distant visual acuity (CDVA and UDVA), and mean absolute error (MAE) of refraction were used as primary outcomes. Secondary outcomes included surgically induced astigmatism (SIA), mean effective phacoemulsification time (EPT), phacoemulsification power and circularity of the capsulorhexis. RESULTS: Nine RCTs and fifteen cohort studies including 4,903 eyes (2,861 in the FLACS group and 2,072 in the CPS group) were identified. There were significant differences between the two groups in ECL% at one week, about one month and three months postoperatively, in CCT at one day, about one month postoperatively and at the final follow-up, in CDVA at one week postoperatively, and in UDVA at the final follow-up. Significant differences were also observed in MAE, EPT, phacoemulsification power, and the circularity of capsulorhexis. However, no significant differences were observed in CDVA at one week postoperatively or in surgically induced astigmatism. CONCLUSIONS: Compared to CPS, FLACS is a safer and more effective method for reducing endothelial cell loss and postoperative central corneal thickening as well as achieving better and faster visual rehabilitation and refractive outcomes. However, there is no difference in final CDVA and surgically induced astigmatism between the two groups. PMID- 26999613 TI - Excess Mortality Attributable to Clostridium difficile and Risk Factors for Infection in an Historic Cohort of Hospitalised Patients Followed Up in the United Kingdom Death Register. AB - METHODS: We compared time from hospital admission to death in a probability sample of 100 Clostridium difficile infected cases and a probability sample of 98 non-cases admitted to an English teaching hospital between 2005 and 2007 with follow up in the UK national death register using survival analysis. RESULTS: Clostridium difficile infection was associated with a 50% increased risk of death (Hazard Ratio 1.51 (95% CI: 1.05-2.19 p = 0.03) at between five to eight years in Cox Regression analysis adjusting for age, sex, Charlson comorbidity index, diagnosis of a malignant condition and insertion of a nasogastric tube during admission. Acquisition of Clostridium difficile infection was independently associated with an almost six fold higher odds of being admitted with a diagnosis of infection of any other type (OR 5.79 (2.19, 15.25) p<0.001). CONCLUSIONS: Our results strongly support continued priority being given to improve prevention and treatment of Clostridium difficile infection in the English National Health Service particularly in patients admitted with an infection. Our results may be applicable to other health systems. PMID- 26999614 TI - Evolution of Collective Behaviors for a Real Swarm of Aquatic Surface Robots. AB - Swarm robotics is a promising approach for the coordination of large numbers of robots. While previous studies have shown that evolutionary robotics techniques can be applied to obtain robust and efficient self-organized behaviors for robot swarms, most studies have been conducted in simulation, and the few that have been conducted on real robots have been confined to laboratory environments. In this paper, we demonstrate for the first time a swarm robotics system with evolved control successfully operating in a real and uncontrolled environment. We evolve neural network-based controllers in simulation for canonical swarm robotics tasks, namely homing, dispersion, clustering, and monitoring. We then assess the performance of the controllers on a real swarm of up to ten aquatic surface robots. Our results show that the evolved controllers transfer successfully to real robots and achieve a performance similar to the performance obtained in simulation. We validate that the evolved controllers display key properties of swarm intelligence-based control, namely scalability, flexibility, and robustness on the real swarm. We conclude with a proof-of-concept experiment in which the swarm performs a complete environmental monitoring task by combining multiple evolved controllers. PMID- 26999615 TI - Multi-scale patch and multi-modality atlases for whole heart segmentation of MRI. AB - A whole heart segmentation (WHS) method is presented for cardiac MRI. This segmentation method employs multi-modality atlases from MRI and CT and adopts a new label fusion algorithm which is based on the proposed multi-scale patch (MSP) strategy and a new global atlas ranking scheme. MSP, developed from the scale space theory, uses the information of multi-scale images and provides different levels of the structural information of images for multi-level local atlas ranking. Both the local and global atlas ranking steps use the information theoretic measures to compute the similarity between the target image and the atlases from multiple modalities. The proposed segmentation scheme was evaluated on a set of data involving 20 cardiac MRI and 20 CT images. Our proposed algorithm demonstrated a promising performance, yielding a mean WHS Dice score of 0.899 +/- 0.0340, Jaccard index of 0.818 +/- 0.0549, and surface distance error of 1.09 +/- 1.11 mm for the 20 MRI data. The average runtime for the proposed label fusion was 12.58 min. PMID- 26999616 TI - Regression forest-based automatic estimation of the articular margin plane for shoulder prosthesis planning. AB - In shoulder arthroplasty, the proximal humeral head is resected by sawing along the cartilage-bone transition and replaced by a prosthetic implant. The resection plane, called articular margin plane (AMP), defines the orientation, position and size of the prosthetic humeral head in relation to the humeral shaft. Therefore, the correct definition of the AMP is crucial for the computer-assisted preoperative planning of shoulder arthroplasty. We present a fully automated method for estimating the AMP relying only on computed tomography (CT) images of the upper arm. It consists of two consecutive steps, each of which uses random regression forests (RFs) to establish a direct mapping from the CT image to the AMP parameters. In the first step, image intensities serve as features to compute a coarse estimate of the AMP. The second step builds upon this estimate, calculating a refined AMP using novel feature types that combine a bone enhancing sheetness measure with ray features. The proposed method was evaluated on a dataset consisting of 72 CT images of upper arm cadavers. A mean localization error of 2.40mm and a mean angular error of 6.51 degrees was measured compared to manually annotated ground truth. PMID- 26999617 TI - The clinical relevance and prognostic significance of microsomal epoxide hydrolase gene polymorphisms and their susceptibility to acquired aplastic anemia: an Egyptian study. AB - BACKGROUND: Microsomal epoxide hydrolase enzyme (mEPHX) is involved in xenobiotics detoxification. Two variants of mEPHX, Tyr113His and His139Arg, have been described. Both may lead to acquired aplastic anemia (AA). OBJECTIVES: Assessing mEPHX genetic polymorphisms and detecting their impact on susceptibility and prognosis in Egyptian AA patients. PARTICIPANTS AND METHODS: mEPHX 113 and 139 genotypes were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 100 patients with AA and 100 control subjects. RESULTS: Both mEPHX Tyr113His and His139Arg gene polymorphisms were associated with increased risk of developing AA, and have a significant impact of bad prognosis (p value < 0.01). CONCLUSIONS: These mEPHX gene polymorphisms can be considered as risk factors and predictive molecular markers for prognosis in AA patients. PMID- 26999618 TI - Implication of Rho-kinase and soluble guanylyl cyclase enzymes in prostate smooth muscle dysfunction in middle-aged rats. AB - AIMS: Aging is highly associated with benign prostate hyperplasia (BPH). We investigated here the alterations of the contractile and relaxant machinery in prostates of middle-aged rats, focusing on the Rho-kinase, nitric oxide (NO) soluble guanylyl cyclase (sGC), alpha1- and beta-adrenoceptor pathways. METHODS: Male Wistar young (3.5-month old) and middle-aged rats (10-month old) were used. Quantitative image analysis of prostates and functional assays evaluating the prostate contractions and relaxations were employed. Measurement of [3 H] noradrenaline efflux, western blotting for alpha1 and beta1 sGC subunits, and cyclic nucleotide levels were carried out. RESULTS: Prostates of middle-aged rats showed significant increases in lumen and smooth muscle cells, but no alterations in the relative prostate weight were observed. In vivo, noradrenaline (10-7 -10-4 g/kg) produced greater prostatic contractions in middle-aged compared with control rats. Likewise, the in vitro contractions to phenylephrine (1 nM-100 MUM) and alpha,beta-methylene ATP (1-10 MUM) were greater in middle-aged rats. Electrical-field stimulation (EFS, 1-32 Hz) promoted higher [3 H]-noradrenaline efflux and prostate contractions in middle-aged rats. Reduced expressions of alpha1 and beta1 sGC subunits and diminished NO-mediated prostate relaxations in middle-age were observed. Isoproterenol-induced relaxations and cAMP levels were reduced in prostates of middle-aged rats. The Rho-kinase inhibitor fasudil (50 mg/kg, 2 weeks) normalized the prostate hypercontractility in middle-age rats. CONCLUSIONS: Prostate hypercontractility in middle-aging is associated with increased release of noradrenaline and Rho-kinase pathway, as well as with impairments of NO-sGC and beta-adrenoceptor pathways. Middle-aged rats are suitable to explore the enhanced prostatic tone in the absence of prostate overgrowth. Neurourol. Urodynam. 36:589-596, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26999619 TI - Relationship between ventricular pressure and coronary artery disease in asymptomatic adult heart transplant recipients. AB - INTRODUCTION: The association between data of right heart catheterization and cardiac allograft vasculopathy (CAV) in adult heart transplant (HTx) recipients remains to be determined. METHODS AND RESULTS: This is an observational, retrospective study, including all consecutive asymptomatic HTx patients undergoing routine right and left catheterization. The independent predictive power of pulmonary capillary wedge pressure (PCWP) to predict CAV (classified according to working formulation of a standardized nomenclature for CAV-2010) was the primary end point. Seventy-one patients were included, with a mean time from HTx to procedure of 19 +/- 25 months. At coronary angiography first degree of CAV was found in eight patients (11.2%), second degree of CAV in two patients (2.8%), and third in two (2.8%). PCWP values were significantly higher in patients with CAV compared with patients without CAV (17.5 +/- 7.5 vs. 10.4 +/- 5.6, P < 0.001) and values of 15 mmHg or greater had an AUC of 0.71 (0.48-0.92), with a sensitivity of 71% and a specificity of 73% in predicting CAV, with an independent relationship confirmed at logistic regression analysis (odds ratio 1.28, IC 1.06-1.53; P = 0.008). CONCLUSION: A significantly elevated PCWP at the time of the diagnosis of transplant coronary artery disease may be considered as an early marker of CAV, especially in asymptomatic HTx recipients. PMID- 26999620 TI - Influence of the overall stiffness of a load-bearing porous titanium implant on bone ingrowth in critical-size mandibular bone defects in sheep. AB - The aim of this work was to assess the influence of reduction of the apparent mechanical properties of fully load-bearing porous titanium implants used in mandibular bone defects. Segmental 18mm long bone defects were created bilaterally in the lower jaws of adult ewes. One group of 6 ewes (group A) was treated with load-bearing 'rigid' (high stiffness) porous implants on the right side, and with control on the left side. A second group of 6 ewes (group B) was treated with 'flexible' porous and control implants exhibiting apparent mechanical properties ten times lower than the rigid implants. The mechanical behavior of the reconstructed hemi-mandibles was assessed by cantilever testing and bone ingrowth into the segmental defects was assessed by BV/TV measurement within the implant using micro-CT 12 weeks after implantation. A significantly higher rigidity was identified for porous implants compared with control implants at the anterior interface in group B. BV/TV of porous implants was significantly higher than that of control implants in group A. BV/TV differences were significant between porous and control implants in group B and were homogeneous along the main axis. Significantly higher BV/TV was identified in most sub volumes of group B porous implants compared with group A. This work highlights the critical importance of the tuning of scaffolds to promote bone ingrowth with reference to the local strains occurring within the porous scaffold, which in this application was achieved using fully load-bearing low-stiffness porous titanium implants. PMID- 26999621 TI - Fabrication of low-cost beta-type Ti-Mn alloys for biomedical applications by metal injection molding process and their mechanical properties. AB - Titanium and its alloys are suitable for biomedical applications owing to their good mechanical properties and biocompatibility. Beta-type Ti-Mn alloys (8-17 mass% Mn) were fabricated by metal injection molding (MIM) as a potential low cost material for use in biomedical applications. The microstructures and mechanical properties of the alloys were evaluated. For up to 13 mass% Mn, the tensile strength (1162-938MPa) and hardness (308-294HV) of the MIM fabricated alloys are comparable to those of Ti-Mn alloys fabricated by cold crucible levitation melting. Ti-9Mn exhibits the best balance of ultimate tensile strength (1046MPa) and elongation (4.7%) among the tested alloys, and has a Young's modulus of 89GPa. The observed low elongation of the alloys is attributed to the combined effects of high oxygen content, with the presence of interconnected pores and titanium carbides, the formation of which is due to carbon pickup during the debinding process. The elongation and tensile strength of the alloys decrease with increasing Mn content. The Ti-Mn alloys show good compressive properties, with Ti-17Mn showing a compressive 0.2% proof stress of 1034MPa, and a compressive strain of 50%. PMID- 26999622 TI - PCR-free and label-free fluorescent detection of telomerase activity at single cell level based on triple amplification. AB - As a universal biomarker for cancer diagnostics and cancer therapeutics, telomerase has attracted extensive attention concerning its detection and discovery of its inhibitors. Herein, we developed a PCR-free and label-free fluorescent strategy for facile, reliable and highly sensitive assay of human telomerase activity from crude cancer cell extracts. A G-quadruplex-selective fluorescent dye, N-methyl mesoporphyrin IX (NMM), was utilized as signal probe. Two hairpin probes with hidden G-quadruplex strand in their stem were designed as assembly components of strand displacement reaction (SDR). In this strategy, one telomerase elongation product contains several hexamer repeats which can hybridize with numerous assistant DNA to release a lot of trigger DNA (T-DNA) of SDR for achieving first step amplification. Then, strand displacement reaction led to the formation of G-quadruplex at the both end of two hairpin DNA probes for realizing second step amplification. Finally, the re-released T-DNA initiated another cycle of SDR, resulting in a significant increase in the fluorescence intensity of NMM. By taking advantage of triple signal amplification, the telomerase activity in the HeLa extracts equivalent to 1-3000 cells was detected in homogeneous solution. Telomerase activities of different cell lines, including cancer cells and normal cell, were also successfully evaluated. Meanwhile, the inhibition effect of 3'-azido-3'-deoxythymidine (AZT) was also investigated. Therefore, it offers a simple and reliable method for detecting telomerase activity at single-cell level without complex pre-modification of probe and enzyme auxiliary signal amplification, which has the merits of simplicity, rapid response, low cost and high reliability. PMID- 26999623 TI - First-line low-dose morphine is better for the control of moderate cancer pain than weaker opioids. PMID- 26999624 TI - A study of mild cognitive impairment in veterans: role of hypertension and other confounding factors. AB - INTRODUCTION: Hypertension has shown to be an important risk factor for the decline in cognitive function. Aim of our study is to investigate the presence of cognitive impairment of the elders with hypertension and other confounding factors. METHODS: This study was conducted on 400 veterans who were matched one to-one with the confounding factors for assessing the presence of mild cognitive impairment using both MMSE and Montreal Cognitive Assessment (MoCA). The 13 related factors of patient data were studied. RESULTS: The prevalence rate of cognitive impairment was 29.25%. Age (OR 2.679, 95%CI 1.663-6.875), sleep impairment (OR 1.117, 95%CI 1.754-7.422), uncontrolled hypertension (OR 1.522, 95%CI 1.968-4.454), type 2 diabetes (OR 2.464, 95%CI 1.232-4.931), and hyperlipidaemia (OR 1.411, 95%CI 1.221-8.988) are the risk factors for the cognitive deterioration, while the protective factors are high level of education (OR 0.032, 95%CI 0.007-0.149) and regular exercise (OR 0.307, 95%CI 0.115-0.818). DISCUSSION: Because some vascular disease risk factors, such as hypertension, can be treated effectively, cognitive decline related to these risk factors, and vascular disease per se, may be prevented or its course modified through more aggressive treatment and improved compliance. PMID- 26999625 TI - Acute effects of psychological relaxation techniques between two physical tasks. AB - The concept of recovery strategies includes various ways to achieve a state of well-being, prevent underrecovery syndromes from occurring and re-establish pre performance states. A systematic application of individualised relaxation techniques is one of those. Following a counterbalanced cross-over design, 27 sport science students (age 25.22 +/- 1.08 years; sports participation 8.08 +/- 3.92 h/week) were randomly assigned to series of progressive muscle relaxation, systematic breathing, power nap, yoga, and a control condition. Once a week, over the course of five weeks, their repeated sprint ability was tested. Tests (6 sprints of 4 s each with 20 s breaks between them) were executed on a non motorised treadmill twice during that day intermitted by 25 min breaks. RM-ANOVA revealed significant interaction effects between the relaxation conditions and the two sprint sessions with regard to average maximum speed over all six sprints, F(4,96) = 4.06, P = 0.004, [Formula: see text] = 0.15. Post-hoc tests indicated that after systematic breathing interventions, F(1,24) = 5.02, P = 0.033, [Formula: see text] = 0.18, participants performed significantly better compared to control sessions. As the focus of this study lied on basic mechanisms of relaxation techniques in sports, this randomised controlled trial provides us with distinct knowledge on their effects, i.e., systematic breathing led to better performances, and therefore, seems to be a suited relaxation method during high-intensity training. PMID- 26999626 TI - Digital Relief of the Mental Foramen for a CAD/CAM-Fabricated Mandibular Denture. AB - Relief of the intaglio surface of a denture base is conventionally performed using thin wax and soft metal foil attached to the master cast. The following report highlights a new relief procedure for the mental foramen using a CT double scan technique on the CAD/CAM dentures fabricated for the patient with paresthesia of the left lower lip and chin during mastication. PMID- 26999627 TI - The microbiome as a possible target to prevent celiac disease. PMID- 26999628 TI - Elemental bioimaging and speciation analysis for the investigation of Wilson's disease using MUXRF and XANES. AB - A liver biopsy specimen from a Wilson's disease (WD) patient was analyzed by means of micro-X-ray fluorescence (MUXRF) spectroscopy to determine the elemental distribution. First, bench-top MUXRF was utilized for a coarse scan of the sample under laboratory conditions. The resulting distribution maps of copper and iron enabled the determination of a region of interest (ROI) for further analysis. In order to obtain more detailed elemental information, this ROI was analyzed by synchrotron radiation (SR)-based MUXRF with a beam size of 4 MUm offering a resolution at the cellular level. Distribution maps of additional elements to copper and iron like zinc and manganese were obtained due to a higher sensitivity of SR-MUXRF. In addition to this, X-ray absorption near edge structure spectroscopy (XANES) was performed to identify the oxidation states of copper in WD. This speciation analysis indicated a mixture of copper(i) and copper(ii) within the WD liver tissue. PMID- 26999630 TI - Cancer in Adolescents and Young Adults: A Narrative Review of the Current Status and a View of the Future. AB - IMPORTANCE: Although cancer remains the most common cause of disease-related death in adolescents and young adults (AYAs) in high-income countries, their overall survival rates continue to increase and now exceed 80% at 5 years in several high-income countries. This has been accomplished through progressive improvements in active treatment and supportive care, although accrual rates to therapeutic clinical trials remain disappointing. Recognition of the unique distribution of diseases in the AYA population with cancer and further understanding of the distinctive biology of cancers in AYAs will lead to continuing gains in clinical outcomes. OBSERVATIONS: Many of the challenges faced by AYAs with a diagnosis of malignant disease are shared by others with chronic medical conditions and even their healthy peers, such as a sense of invulnerability that may contribute to delays in diagnosis. A particular need for psychological support has been identified for AYAs with cancer, even after active therapy has been completed and especially in the context of palliative care. Notable needs also include fertility preservation and navigation through the multiple transitions in the cancer journey. Additionally, there is a "cost of cure." This is not only in the form of short-term, treatment-related morbidity and mortality but also in the burden of "late effects," including second cancers, that compromise quality of life and limit life expectancy. Establishing clinical programs devoted to AYAs with cancer, with complementary educational initiatives, will strengthen the advances made. It is anticipated that clinical trial accrual will increase substantially, providing further gains in survival. Likewise, addressing the challenges of survivorship, including secondary prevention of long term morbidity and mortality, will lead to additional improvements in clinical outcomes. CONCLUSIONS AND RELEVANCE: Transferring this knowledge to the care of an estimated 1 million incident cases of cancer in AYAs worldwide, most of whom do not live in high-income countries, remains a considerable challenge. PMID- 26999629 TI - RpoS is required for natural transformation of Vibrio cholerae through regulation of chitinases. AB - Vibrio species naturally reside in the aquatic environment and a major metabolite in this habitat is the chitinous exoskeletons of crustacean zooplankton. In addition to serving as a nutrient, chitin-derived oligosaccharides also induce natural genetic competence in many Vibrio spp., a physiological state in which bacteria take up DNA from the extracellular environment and can integrate it into their chromosome by homologous recombination. Another inducing cue required for competence are quorum-sensing autoinducers. The alternative sigma factor RpoS is critical for natural transformation in Vibrio cholerae, and it was previously presumed to exert this effect through regulation of quorum sensing. Here, we show that RpoS does not affect quorum sensing-dependent regulation of competence. Instead, we show that an rpoS mutant has reduced chitinase activity, which is required to liberate the soluble chitin oligosaccharides that serve as an inducing cue for competence. Consistent with this, we demonstrate that RpoS is required for growth of V. cholerae on insoluble chitin. RpoS also regulates the mucosal escape response in pathogenic strains of V. cholerae. Thus, in addition to promoting egress from its human host, RpoS may also prime this pathogen for successful reentry into the aquatic environment. PMID- 26999631 TI - The intergenerational transmission of problem gambling: The mediating role of parental psychopathology. AB - The present study investigated the intergenerational transmission of problem gambling and the potential mediating role of parental psychopathology (problem drinking, drug use problems, and mental health issues). The study comprised 3953 participants (1938 males, 2015 females) recruited from a large-scale Australian community telephone survey of adults retrospectively reporting on parental problem gambling and psychopathology during their childhood. Overall, 4.0% [95%CI 3.0, 5.0] (n=157) of participants reported paternal problem gambling and 1.7% [95%CI 1.0, 2.0] (n=68) reported maternal problem gambling. Compared to their peers, participants reporting paternal problem gambling were 5.1 times more likely to be moderate risk gamblers and 10.7 times more likely to be problem gamblers. Participants reporting maternal problem gambling were 1.7 times more likely to be moderate risk gamblers and 10.6 times more likely to be problem gamblers. The results revealed that the relationships between paternal-and participant and maternal-and-participant problem gambling were significant, but that only the relationship between paternal-and-participant problem gambling remained statistically significant after controlling for maternal problem gambling and sociodemographic factors. Paternal problem drinking and maternal drug use problems partially mediated the relationship between paternal-and participant problem gambling, and fully mediated the relationship between maternal-and-participant problem gambling. In contrast, parental mental health issues failed to significantly mediate the transmission of gambling problems by either parent. When parental problem gambling was the mediator, there was full mediation of the effect between parental psychopathology and offspring problem gambling for fathers but not mothers. Overall, the study highlights the vulnerability of children from problem gambling households and suggests that it would be of value to target prevention and intervention efforts towards this cohort. PMID- 26999632 TI - Preparation and Protonation of Fe2(pdt)(CNR)6, Electron-Rich Analogues of Fe2(pdt)(CO)6. AB - The complexes Fe2(pdt)(CNR)6 (pdt(2-) = CH2(CH2S(-))2) were prepared by thermal substitution of the hexacarbonyl complex with the isocyanides RNC for R = C6H4-4 OMe (1), C6H4-4-Cl (2), Me (3). These complexes represent electron-rich analogues of the parent Fe2(pdt)(CO)6. Unlike most substituted derivatives of Fe2(pdt)(CO)6, these isocyanide complexes are sterically unencumbered and have the same idealized symmetry as the parent hexacarbonyl derivatives. Like the hexacarbonyls, the stereodynamics of 1-3 involve both turnstile rotation of the Fe(CNR)3 as well as the inversion of the chair conformation of the pdt ligand. Structural studies indicate that the basal isocyanide has nonlinear CNC bonds and short Fe-C distances, indicating that they engage in stronger Fe-C pi-backbonding than the apical ligands. Cyclic voltammetry reveals that these new complexes are far more reducing than the hexacarbonyls, although the redox behavior is complex. Estimated reduction potentials are E1/2 ~ -0.6 ([2](+/0)), -0.7 ([1](+/0)), and 1.25 ([3](+/0)). According to DFT calculations, the rotated isomer of 3 is only 2.2 kcal/mol higher in energy than the crystallographically observed unrotated structure. The effects of rotated versus unrotated structure and of solvent coordination (THF, MeCN) on redox potentials were assessed computationally. These factors shift the redox couple by as much as 0.25 V, usually less. Compounds 1 and 2 protonate with strong acids to give the expected MU-hydrides [H1](+) and [H2](+). In contrast, 3 protonates with [HNEt3]BAr(F)4 (pKa(MeCN) = 18.7) to give the aminocarbyne [Fe2(pdt)(CNMe)5(MU-CN(H)Me)](+) ([3H](+)). According to NMR measurements and DFT calculations, this species adopts an unsymmetrical, rotated structure. DFT calculations further indicate that the previously described carbyne complex [Fe2(SMe)2(CO)3(PMe3)2(CCF3)](+) also adopts a rotated structure with a bridging carbyne ligand. Complex [3H](+) reversibly adds MeNC to give [Fe2(pdt)(CNR)6(MU-CN(H)Me)](+) ([3H(CNMe)](+)). Near room temperature, [3H](+) isomerizes to the hydride [(MU-H)Fe2(pdt)(CNMe)6](+) ([H3](+)) via a first-order pathway. PMID- 26999633 TI - Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification. AB - BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to >=2 panallergens ('multi panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice. PMID- 26999634 TI - Occupation as a risk factor for renal cell cancer: a nationwide, prospective epidemiological study. AB - Objective Using centralized registries in Iceland, the aim of this study was to prospectively investigate multiple risk factors for renal cell carcinoma (RCC), including occupational history. Materials and methods From the Reykjavik study database, 18,840 men and women born in the period 1907-1935 were linked with a population-based registry containing all RCCs diagnosed in Iceland from 1971 to 2005 (n = 910). From this cross-reference, altogether 225 cases were identified. A prospective analysis of the risk factors for RCC was performed using Cox regression analysis, from the time of entry into the Reykjavik study to the diagnosis of RCC, death or end of follow-up, with a median follow-up time of 25 years. The hazard ratio (HR) was then calculated for multiple risk factors including occupational history. Results Male gender [HR 1.65, 95% confidence interval (CI) 1.14-2.38], body mass index (BMI) over 25 kg/m2 (HR 1.41, 95% CI 1.06-1.88) and age (HR 1.04, 95% CI 1.03-1.07) increased the risk of RCC, as did severe hypertension (>160/100 mmHg) (HR 1.46, 95% CI 1.05-2.03) and history of kidney disease (HR 1.55, 95% CI 1.11-2.16); however, smoking and type 2 diabetes were not significantly associated with the disease. The risk of RCC was significantly increased in painters (HR 2.97, 95% CI 1.31-6.74), aircraft mechanics (HR 4.51, 95% CI 1.11-18.28) and shipbuilders (HR 2.03, 95% CI 1.06 3.84). Conclusions Together with male gender, advanced age, hypertension, BMI over 25 kg/m2 and history of kidney disease, the risk of RCC was significantly increased in painters, aircraft mechanics and shipbuilders, suggesting a link to occupational exposure. PMID- 26999635 TI - Single nucleotide polymorphism array analysis of clonal evolution in younger adult acute lymphoblastic leukemia. PMID- 26999636 TI - Organic Photovoltaics and Bioelectrodes Providing Electrical Stimulation for PC12 Cell Differentiation and Neurite Outgrowth. AB - Current bioelectronic medicines for neurological therapies generally involve treatment with a bioelectronic system comprising a power supply unit and a bioelectrode device. Further integration of wireless and self-powered units is of practical importance for implantable bioelectronics. In this study, we developed biocompatible organic photovoltaics (OPVs) for serving as wireless electrical power supply units that can be operated under illumination with near-infrared (NIR) light, and organic bioelectronic interface (OBEI) electrode devices as neural stimulation electrodes. The OPV/OBEI integrated system is capable to provide electrical stimulation (ES) as a means of enhancing neuron-like PC12 cell differentiation and neurite outgrowth. For the OPV design, we prepared devices incorporating two photoactive material systems--beta-carotene/N,N'-dioctyl 3,4,9,10-perylenedicarboximide (beta-carotene/PTCDI-C8) and poly(3 hexylthiophene)/phenyl-C61-butyric acid methyl ester (P3HT/PCBM)--that exhibited open circuit voltages of 0.11 and 0.49 V, respectively, under NIR light LED (NLED) illumination. Then, we connected OBEI devices with different electrode gaps, incorporating biocompatible poly(hydroxymethylated-3,4 ethylenedioxythiophene), to OPVs to precisely tailor the direct current electric field conditions during the culturing of PC12 cells. This NIR light-driven OPV/OBEI system could be engineered to provide tunable control over the electric field (from 220 to 980 mV mm(-1)) to promote 64% enhancement in the neurite length, direct the neurite orientation on chips, or both. The OPV/OBEI integrated systems under NIR illumination appear to function as effective power delivery platforms that should meet the requirements for wirelessly offering medical ES to a portion of the nervous system; they might also be a key technology for the development of next-generation implantable bioelectronics. PMID- 26999637 TI - One-Pot Synthesis and Evaluation of Antileishmanial Activities of Functionalized S-Alkyl/Aryl Benzothiazole-2-carbothioate Scaffold. AB - The synthesis of hitherto unreported S-alkyl/aryl benzothiazole-2-carbothioate is reported from thiols, oxalyl chloride, and 2-aminothiophenols using 10 mol % n tetrabutylammonium iodide (TBAI) as catalyst in acetonitrile through multicomponent reaction (MCR) strategy. The present protocol favored formation of benzothiazoles and thioesters via simultaneous formation of C-N and C-S bonds in good yields with a wide range of substrates. A few of the synthesized derivatives were evaluated for their antimicrobial activity against the protozoan parasite Leishmania donovani, a causative agent of visceral leishmaniasis (VL). Further, these compounds displayed no toxicity toward macrophage RAW 264.7 cells and are therefore nontoxic and effective antileishmanial leads. In silico docking studies were performed to understand the possible binding site interaction with trypanothione reductase (TryR). PMID- 26999638 TI - Tandem C(sp(2))-OMe Activation/C(sp(2))-C(sp(2)) Coupling in Early Transition Metal Complexes: Aromatic C-O Activation beyond Late Transition Metals. AB - We report on combined structural, kinetic, and computational studies unraveling the mechanism of a unique, highly selective intramolecular C(sp(2))-OMe cleavage/C(sp(2))-C(sp(2)) coupling tandem reaction in group 3 metal (Y and Sc) complexes of amidine-amidopyridinate ligands. The latter process represents a rare stoichiometric model of the nonredox cleavage of inert C(sp(2))-O bonds relevant to cross-coupling reactions of aromatic ethers catalyzed by late transition metals. PMID- 26999639 TI - Control of Respiratory Drive and Effort in Extracorporeal Membrane Oxygenation Patients Recovering from Severe Acute Respiratory Distress Syndrome. AB - BACKGROUND: The amount of extracorporeal carbon dioxide removal may influence respiratory drive in acute respiratory distress syndrome (ARDS) patients undergoing extracorporeal membrane oxygenation (ECMO). The authors evaluated the effects of different levels of extracorporeal carbon dioxide removal in patients recovering from severe ARDS undergoing pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). METHODS: The authors conducted a prospective, randomized, crossover study on eight spontaneously breathing ARDS patients undergoing venovenous ECMO since 28 +/- 20 days. To modulate carbon dioxide extraction, ECMO gas flow (GF) was decreased from baseline resting protective conditions (i.e., GF100%, set to obtain pressure generated in the first 100 ms of inspiration against an occluded airway less than 2 cm H2O, respiratory rate less than or equal to 25 bpm, tidal volume less than 6 ml/kg, and peak airway pressure less than 25 cm H2O) to GF50%-GF25%-GF0% during both PSV and NAVA (random order for ventilation mode). Continuous recordings of airway pressure and flow and esophageal pressure were obtained and analyzed during all study phases. RESULTS: At higher levels of extracorporeal carbon dioxide extraction, pressure generated in the first 100 ms of inspiration against an occluded airway decreased from 2.8 +/- 2.7 cm H2O (PSV, GF0%) and 3.0 +/- 2.1 cm H2O (NAVA, GF0%) to 0.9 +/- 0.5 cm H2O (PSV, GF100%) and 1.0 +/- 0.8 cm H2O (NAVA, GF100%; P < 0.001) and patients' inspiratory muscle pressure passed from 8.5 +/- 6.3 and 6.5 +/- 5.5 cm H2O to 4.5 +/- 3.1 and 4.2 +/- 3.7 cm H2O (P < 0.001). In time, decreased inspiratory drive and effort determined by higher carbon dioxide extraction led to reduction of tidal volume from 6.6 +/- 0.9 and 7.5 +/- 1.2 ml/kg to 4.9 +/- 0.8 and 5.3 +/- 1.3 ml/kg (P < 0.001) and of peak airway pressure from 21 +/- 3 and 25 +/- 4 cm H2O to 21 +/- 3 and 21 +/- 5 cm H2O (P < 0.001). Finally, transpulmonary pressure linearly decreased when the amount of carbon dioxide extracted by ECMO increased (R = 0.823, P < 0.001). CONCLUSIONS: In patients recovering from ARDS undergoing ECMO, the amount of carbon dioxide removed by the artificial lung may influence spontaneous breathing. The effects of carbon dioxide removal on spontaneous breathing during the earlier acute phases of ARDS remain to be elucidated. PMID- 26999640 TI - Association between Lp (a) and atherosclerosis in menopausal women without metabolic syndrome. AB - AIM: The association between Lipoprotein (a) (Lp [a]) and common carotid intima media thickness (IMT) has been evaluated in 222 menopausal women. MATERIAL & METHODS: Lp (a) and IMT were measured, carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. RESULTS: Lp (a) was significantly lower in women with metabolic syndrome (MS). In a multivariate analysis Lp (a) showed the following odds ratio (OR; all p < 0.05) of having common carotid IMT (>=1.30 mm): 1.03, adjusted for age, low-density lipoprotein cholesterol (LDL) and waist circumference; 1.02, adjusted for age LDL, homeostatic assessment model (HOMA). In women without MS, after controlling for age, LDL and waist circumference, we found the following OR for increased IMT (>=1.30; OR: 1.03; for Lp [a]); 1.02 adjusted for age, LDL and HOMA (all p < 0.05). In women with MS these relationships were not statistically significant. CONCLUSION: Lp (a) gives additional information in the risk assessment for atherosclerotic cardiovascular disease, especially in menopausal women without MS. PMID- 26999642 TI - The use of SHP-2 gene transduced bone marrow mesenchymal stem cells to promote osteogenic differentiation and bone defect repair in rat. AB - Bone tissue engineering is a promising approach for bone regeneration, in which growth factors play an important role. The tyrosine phosphatase Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by the PTPN11 gene, is essential for the differentiation, proliferation and metabolism of osteoblasts. However, SHP-2 has never been systematically studied for its effect in osteogenesis. We predicted that overexpression of SHP-2 could promote bone marrow-derived mesenchymal stem cell (BMSC)osteogenic differentiation and SHP-2 transduced BMSCs could enhance new bone formation, determined using the following study groups: (1) BMSCs transduced with SHP-2 and induced with osteoblast inducing liquid (BMSCs/SHP-2/OL); (2) BMSCs transduced with SHP-2 (BMSCs/-SHP-2); (3) BMSCs induced with osteoblast-inducing liquid (BMSCs/OL) and (4) pure BMSCs. Cells were assessed for osteogenic differentiation by quantitative real-time polymerase chain reaction analysis, western blot analysis, alkaline phosphatase activity and alizarin red S staining. For in vivo assessment, cells were combined with beta-tricalcium phosphate scaffolds and transplanted into rat calvarial defects for 8 weeks. Following euthanasia, skull samples were explanted for osteogenic evaluation, including micro-computed tomography measurement, histology and immunohistochemistry staining. SHP-2 and upregulation of its gene promoted BMSC osteogenic differentiation and therefore represents a potential new therapeutic approach to bone repair. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1871-1881, 2016. PMID- 26999643 TI - Polar-Graded Multiferroic SrMnO3 Thin Films. AB - Engineering defects and strains in oxides provides a promising route for the quest of thin film materials with coexisting ferroic orders, multiferroics, with efficient magnetoelectric coupling at room temperature. Precise control of the strain gradient would enable custom tailoring of the multiferroic properties but presently remains challenging. Here we explore the existence of a polar-graded state in epitaxially strained antiferromagnetic SrMnO3 thin films, whose polar nature was predicted theoretically and recently demonstrated experimentally. By means of aberration-corrected scanning transmission electron microscopy we map the polar rotation of the ferroelectric polarization with atomic resolution, both far from and near the domain walls, and find flexoelectricity resulting from vertical strain gradients. The origin of this particular strain state is a gradual distribution of oxygen vacancies across the film thickness, according to electron energy loss spectroscopy. Herein we present a chemistry-mediated route to induce polar rotations in oxygen-deficient multiferroic films, resulting in flexoelectric polar rotations and with potentially enhanced piezoelectricity. PMID- 26999641 TI - Aberrant activation of the PI3K/mTOR pathway promotes resistance to sorafenib in AML. AB - Therapy directed against oncogenic FLT3 has been shown to induce response in patients with acute myeloid leukemia (AML), but these responses are almost always transient. To address the mechanism of FLT3 inhibitor resistance, we generated two resistant AML cell lines by sustained treatment with the FLT3 inhibitor sorafenib. Parental cell lines carry the FLT3-ITD (tandem duplication) mutation and are highly responsive to FLT3 inhibitors, whereas resistant cell lines display resistance to multiple FLT3 inhibitors. Sanger sequencing and protein mass-spectrometry did not identify any acquired mutations in FLT3 in the resistant cells. Moreover, sorafenib treatment effectively blocked FLT3 activation in resistant cells, whereas it was unable to block colony formation or cell survival, suggesting that the resistant cells are no longer FLT3 dependent. Gene expression analysis of sensitive and resistant cell lines, as well as of blasts from patients with sorafenib-resistant AML, suggested an enrichment of the PI3K/mTOR pathway in the resistant phenotype, which was further supported by next generation sequencing and phospho-specific-antibody array analysis. Furthermore, a selective PI3K/mTOR inhibitor, gedatolisib, efficiently blocked proliferation, colony and tumor formation, and induced apoptosis in resistant cell lines. Gedatolisib significantly extended survival of mice in a sorafenib-resistant AML patient-derived xenograft model. Taken together, our data suggest that aberrant activation of the PI3K/mTOR pathway in FLT3-ITD-dependent AML results in resistance to drugs targeting FLT3. PMID- 26999646 TI - Effective clean-up of organic liquid contaminants including BTEX, fuels, and organic solvents from the environment by poly(alkoxysilane) sorbents. AB - Novel cross-linked poly(alkoxysilane)s, which can be used for the removal of organic liquid contaminants from water, were synthesized in one step, in a solvent free reaction medium, at moderately high temperature without using a catalyst. The synthesized polymers were characterized by Fourier transform infrared spectroscopy (FTIR), solid-state (13)C and (29)Si cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR), thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) methods and elemental analysis. The swelling features of the poly(alkoxysilane)s were investigated in organic solvents and oils, such as dichloromethane, benzene, toluene, xylene, methyl tertiary butyl ether, and also some fuel derivatives, such as gasoline and euro diesel. All polymers have high-fast solvent uptake abilities, good reusability and thermal stability. The swelling features of the synthesized cross-linked polymers were evaluated by the swelling test, absorption desorption kinetics. Thus, the results propose that cross-linked poly(alkoxysilane)s are suitable for the absorption of oil-organic pollutants from the water surface. PMID- 26999645 TI - Effect of Repeated Active Recovery During a High-Intensity Interval-Training Shock Microcycle on Markers of Fatigue. AB - PURPOSE: To investigate the effect of repeated use of active recovery during a 4 d shock microcycle with 7 high-intensity interval-training (HIT) sessions on markers of fatigue. METHODS: Eight elite male junior tennis players (age 15.1 +/- 1.4 y) with an international ranking between 59 and 907 (International Tennis Federation) participated in this study. After each training session, they completed 15 min of either moderate jogging (active recovery [ACT]) or passive recovery (PAS) with a crossover design, which was interrupted by a 4-mo washout period. Countermovement-jump (CMJ) height, serum concentration of creatine kinase (CK), delayed-onset muscle soreness (DOMS), and perceived recovery and stress (Short Recovery and Stress Scale) were measured 24 h before and 24 h after the training program. RESULTS: The HIT shock microcycle induced a large decrease in CMJ performance (ACT: effect size [ES] = -1.39, P < .05; PAS: ES = -1.42, P < .05) and perceived recovery (ACT: ES = -1.79, P < .05; PAS: ES = -2.39, P < .05), as well as a moderate to large increase in CK levels (ACT: ES = 0.76, P > .05; PAS: ES = 0.81, P >.05), DOMS (ACT: ES = 2.02, P < .05; PAS: ES = 2.17, P < .05), and perceived stress (ACT: ES = 1.98, P < .05; PAS: ES = 3.06, P < .05), compared with the values before the intervention. However, no significant recovery intervention * time interactions or meaningful differences in changes were noted in any of the markers between ACT and PAS. CONCLUSIONS: Repeated use of individualized ACT, consisting of 15 min of moderate jogging, after finishing each training session during an HIT shock microcycle did not affect exercise induced fatigue. PMID- 26999647 TI - Low-Flow Vascular Malformation Pitfalls: From Clinical Examination to Practical Imaging Evaluation--Part 2, Venous Malformation Mimickers. AB - OBJECTIVE: The purpose of this article is to review the unusual clinical and radiographic features of venous malformations that can give rise to diagnostic confusion. Entities that can have overlapping clinical and imaging features with venous malformations are also reviewed. CONCLUSION: Venous malformations are congenital endothelial malformations secondary to errors in vascular morphogenesis and are usually diagnosed in the first 2 decades of life. The clinical and imaging features of venous malformations often overlap those of other pathologic entities, creating diagnostic confusion. Furthermore, the clinical presentation and imaging appearance of venous malformations can vary, making the diagnosis challenging. Thorough knowledge of the various clinical and imaging features not only of venous malformations but also of the major potential mimic lesions is crucial for clinicians caring for patients with these lesions. PMID- 26999644 TI - Higher hydrocortisone dose increases bilirubin in hypopituitary patients- results from an RCT. AB - BACKGROUND: Bilirubin has anti-oxidative and anti-inflammatory properties, which may explain its proposed protective effects on the development of cardiometabolic disorders. Glucocorticoids affect heme oxygenase regulation in vitro, which plays a key role in bilirubin production. Effects of variations in glucocorticoid exposure on circulating bilirubin levels in humans are unknown. Here we tested whether a higher hydrocortisone replacement dose affects circulating bilirubin in hypopituitary patients. MATERIALS AND METHODS: A randomized double-blind cross over study (ClinicalTrials.gov, number NCT01546992) was performed in 47 patients with secondary adrenal failure [10-week exposure to a higher hydrocortisone dose (0.4-0.6 mg/kg body weight) vs. 10 weeks of a lower hydrocortisone dose (0.2-0.3 mg/kg body weight)]. RESULTS: Plasma total bilirubin was increased by 10% from 7 to 8 MUM in response to the higher hydrocortisone dose (P = 0.033). This effect was inversely related to age (P = 0.042), but was unaffected by sex, obesity and (replacement for) other hormonal insufficiencies. The higher hydrocortisone dose also resulted in lower alkaline phosphatase (P = 0.006) and aspartate aminotransferase activities (P = 0.001). CONCLUSION: Bilirubin is modestly increased in response to higher glucocorticoid exposure in humans, in conjunction with lower alkaline phosphatase and aspartate aminotransferase activities, which are supposed to represent biomarkers of a pro-inflammatory state and enhanced liver fat accumulation. PMID- 26999648 TI - Intrinsic Catalytic Activity of Graphene Defects for the Co(II/III)(bpy)3 Dye Sensitized Solar Cell Redox Mediator. AB - We demonstrate that functionalized graphene, rich with lattice defects but lean with oxygen sites, catalyzes the reduction of Co(III)(bpy)3 as well as platinum does, exhibiting a rate of heterogeneous electron transfer, k0, of ~6 * 10(-3) cm/s. We show this rate to be an order of magnitude higher than on oxygen-site rich graphene oxide, and over 2 orders of magnitude higher than on the basal plane of graphite (as a surrogate for pristine graphene). Furthermore, dye sensitized solar cells using defect-rich graphene monolayers perform similarly to those using platinum nanoparticles as the catalyst. PMID- 26999650 TI - Dermoscopy in the era of dermato-oncology: from bed to bench side and retour. AB - Today dermoscopy is standard-of-care in the diagnosis and management of patients with benign and malignant skin tumors because it increases the diagnostic accuracy of skin lesions compared to the naked-eye examination up to 25%. Despite its role in the routine dermato-oncology, it increasingly gained interest as a bridge connecting clinical with basic molecular research in dermato-oncology. Here, we correlate dermoscopy patterns of nevi and melanomas with high and low susceptibility genes and somatic mutations, provide an overview on the clinical and dermoscopic patterns of cutaneous melanoma subtypes, and highlight the role of dermoscopy in the diagnosis of skin eruptions during systemic treatments of advanced melanoma including targeted therapies and immunotherapies. PMID- 26999651 TI - Antimicrobial Access in the 21st Century: Delays and Critical Shortages. PMID- 26999652 TI - Stable carbon and nitrogen isotope discrimination and turnover in a small-bodied insectivorous lizard. AB - Laboratory experiments are useful for estimating the carbon and nitrogen isotope discrimination factors and turnover rates that are critical for drawing field based inferences on consumer diets using stable isotopes. Although the utility of these discrimination factors is widely recognized, work in terrestrial systems has largely been limited to studies involving mammals and birds. In contrast, scant attention has been paid to the application of isotopic techniques to reptiles, despite their broad diversity in terms of numbers of species as well as their trophic roles. Here we estimate carbon and nitrogen isotope discrimination factors and turnover for the tree lizard (Urosaurus ornatus) using a diet-switch experiment. Lizards were collected from a C4-dominated grassland and then switched to C3-based diet (crickets) in the laboratory. We estimated discrimination by lizard claw tissue as Delta(13)C = 1.2 +/- 0.1 0/00 for carbon and Delta(15)N = 0.7 +/- 0.1 0/00 (mean +/- 1 SE) for nitrogen, with 95 % turnover occurring after ~15.5 days. These estimates should be appropriate for use in trophic studies of U. ornatus, and possibly other related small-bodied insectivorous lizards. PMID- 26999649 TI - The Role of Nature and Nurture for Individual Differences in Primary Emotional Systems: Evidence from a Twin Study. AB - The present study investigated for the first time the relative importance of genetics and environment on individual differences in primary emotionality as measured with the Affective Neuroscience Personality Scales (ANPS) by means of a twin-sibling study design. In N = 795 participants (n = 303 monozygotic twins, n = 172 dizygotic twins and n = 267 non-twin full siblings), moderate to strong influences of genetics on individual differences in these emotional systems are observed. Lowest heritability estimates are presented for the SEEKING system (33%) and highest for the PLAY system (69%). Further, multivariate genetic modeling was applied to the data showing that associations among the six ANPS scales were influences by both, a genetic as well as an environmental overlap between them. In sum, the study underlines the usefulness of the ANPS for biologically oriented personality psychology research. PMID- 26999653 TI - Ultraviolet radiation protection and skin cancer awareness in recreational athletes: a survey among participants in a running event. AB - PRINCIPLE: Ultraviolet radiation (UVR) protection and skin cancer awareness are essential in the avoidance of cutaneous malignancies. Skin cancer prevention programmes involve public educational campaigns, for example, for outdoor workers or school children. Since nonprofessional sun exposure (e.g. during outdoor sport) is increasing with today's lifestyle, we assessed UVR protection and skin cancer awareness among recreational athletes. This survey-based, paper/pencil study was designed to assess UVR protection and skin cancer awareness among recreational athletes attending the largest running event in Switzerland. METHODS: All adults (age 18 and older) attending this run were invited to complete our survey at our study booth. Our form consisted of questions about participants' personal characteristics such as age, gender, educational attainment, skin type, history of sunburns, and personal/family history of skin cancer, as well as participants' subjective attitudes and behaviours relating to UVR protection and skin cancer avoidance. We calculated separate scores for individual UVR protection and skin cancer awareness. We tested these two scores in relation to educational level as a primary endpoint. In addition, the impacts of further distinct characteristics were assessed in multivariable analysis. RESULTS: A total of 970 runners (457 males, 513 females, mean age 41.0 years) completed our survey. Our results indicate that UVR protection is dependent on age, gender, skin type and personal history of skin cancer. Educational attainment (at univariate level), age, gender and skin type (in multivariable analysis) significantly affected the skin cancer awareness score. CONCLUSION: Our findings suggest that protection measures among recreational sportsmen can be improved. Achievements are notable in older, fair skinned, female runners. Our findings indicate that further work is needed in the education of the general public, and athletes in particular. PMID- 26999654 TI - Synthesis of AB4-type carbohydrate scaffolds as branching units in the glycosciences. AB - Carbohydrate scaffolds, functionalised according to an AB4-type, were prepared on the basis of alpha-D-mannopyranosides with various ethyl aglycone moieties, functionalised with 'A'. Four functional groups 'B' were installed at positions 2, 3, 4, and 6 of the sugar ring. In particular, we were interested in preparing N3(NH2)4-functionalised mannosides as multifunctional branching units for further orthogonal derivatisation or immobilisation on surfaces. A detailed synthetic study was performed which revealed that an azido function 'A' had to be installed at an advanced stage of the synthesis for successful preparation of the desired AB4-type carbohydrate scaffolds. The most successful synthetic sequence involved tetra-cyanoethylation of a 2-benzyloxyethyl mannopyranoside and subsequent reduction with in situ Boc protection to achieve (NHBoc)4 functionalisation. Finally, the benzyloxyethyl aglycon was converted into the corresponding azidoethyl moiety to gain access to the desired N3(NHBoc)4-functionalised carbohydrate scaffold. Its utilisation was exemplified by straightforward synthesis of a photosensitive glycoconjugate and a tetravalent glycocluster. Such compounds may be immobilised on functional surfaces to serve as tools in cell adhesion studies. PMID- 26999655 TI - Assessment of Interradiologist Agreement Regarding Mammographic Breast Density Classification Using the Fifth Edition of the BI-RADS Atlas. AB - OBJECTIVE: The objective of the present study was to assess interradiologist agreement regarding mammographic breast density assessment performed using the rating scale outlined in the fifth edition of the BI-RADS atlas of the American College of Radiology. MATERIALS AND METHODS: Breast density assessments of 1000 cases were conducted by five radiologists from the same institution who together had recently undergone retraining in mammographic breast density classification based on the fifth edition of BI-RADS. The readers assigned breast density grades (A-D) on the basis of the BI-RADS classification scheme. Repeat assessment of 100 cases was performed by all readers 1 month after the initial assessment. A weighted kappa was used to calculate intrareader and interreader agreement. RESULTS: Intrareader agreement ranged from a kappa value of 0.86 (95% CI, 0.77 0.93) to 0.89 (95% CI, 0.81-0.95) on a four-category scale (categories A-D) and from 0.89 (95% CI, 0.86-0.92) to 0.94 (95% CI, 0.89-0.97) on a two-category scale (category A-B vs category C-D). Interreader agreement ranged from substantial (kappa = 0.76; 95% CI, 0.73-0.78) to almost perfect (kappa = 0.87; 95% CI, 0.86 0.89) on a four-category scale, and the overall weighted kappa value was substantial (0.79; 95% CI, 0.78-0.83). Interreader agreement on a two-category scale ranged from a kappa value of 0.85 (95% CI, 0.83-0.86) to 0.91 (95% CI, 0.90 0.92), and the overall weighted kappa was 0.88 (95% CI, 0.87-0.89). CONCLUSION: Overall, with regard to mammographic breast density classification, radiologists had substantial interreader agreement when a four-category scale was used and almost perfect interreader agreement when a dichotomous scale was used. PMID- 26999657 TI - Two-sample tests and one-way MANOVA for multivariate biomarker data with nondetects. AB - Testing whether the mean vector of a multivariate set of biomarkers differs between several populations is an increasingly common problem in medical research. Biomarker data is often left censored because some measurements fall below the laboratory's detection limit. We investigate how such censoring affects multivariate two-sample and one-way multivariate analysis of variance tests. Type I error rates, power and robustness to increasing censoring are studied, under both normality and non-normality. Parametric tests are found to perform better than non-parametric alternatives, indicating that the current recommendations for analysis of censored multivariate data may have to be revised. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999656 TI - Persistence and resistance as complementary bacterial adaptations to antibiotics. AB - Bacterial persistence represents a simple of phenotypic heterogeneity, whereby a proportion of cells in an isogenic bacterial population can survive exposure to lethal stresses such as antibiotics. In contrast, genetically based antibiotic resistance allows for continued growth in the presence of antibiotics. It is unclear, however, whether resistance and persistence are complementary or alternative evolutionary adaptations to antibiotics. Here, we investigate the co evolution of resistance and persistence across the genus Pseudomonas using comparative methods that correct for phylogenetic nonindependence. We find that strains of Pseudomonas vary extensively in both their intrinsic resistance to antibiotics (ciprofloxacin and rifampicin) and persistence following exposure to these antibiotics. Crucially, we find that persistence correlates positively to antibiotic resistance across strains. However, we find that different genes control resistance and persistence implying that they are independent traits. Specifically, we find that the number of type II toxin-antitoxin systems (TAs) in the genome of a strain is correlated to persistence, but not resistance. Our study shows that persistence and antibiotic resistance are complementary, but independent, evolutionary adaptations to stress and it highlights the key role played by TAs in the evolution of persistence. PMID- 26999658 TI - In Situ Loading of Drugs into Mesoporous Silica SBA-15. AB - In a new strategy for loading drugs into mesoporous silica, a hydrophilic (heparin) or hydrophobic drug (ibuprofen) is encapsulated directly in a one-pot synthesis by evaporation-induced self-assembly. In situ drug loading significantly cuts down the preparation time and dramatically increases the loaded amount and released fraction of the drug, and appropriate drug additives favor a mesoporous structure of the vessels. Drug loading was verified by FTIR spectroscopy and release tests, which revealed much longer release with a larger amount of heparin or ibuprofen compared to postloaded SBA-15. Besides, the in vitro anticoagulation properties of the released heparin and the biocompatibility of the vessels were carefully assessed, including activated partial thromboplastin time, thrombin time, hemolysis, platelet adhesion experiments, and the morphologies of red blood cells. A concept of new drug-release agents with soft core and hard shell is proposed and offers guidance for the design of novel drug-delivery systems. PMID- 26999659 TI - Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates. AB - Inflammation and apoptosis are crucial mechanisms for the development of the acute respiratory distress syndrome (ARDS). Currently, there is no specific pharmacological therapy for ARDS. We have evaluated the ability of a new family of 1,2,3,5-tetrasubstituted pyrrol compounds for attenuating lipopolysaccharide (LPS)-induced inflammation and apoptosis in an in vitro LPS-induced airway epithelial cell injury model based on the first steps of the development of sepsis-induced ARDS. Human alveolar A549 and human bronchial BEAS-2B cells were exposed to LPS, either alone or in combination with the pyrrol derivatives. Rhein and emodin, two representative compounds with proven activity against the effects of LPS, were used as reference compounds. The pyrrol compound that was termed DTA0118 had the strongest inhibitory activity and was selected as the lead compound to further explore its properties. Exposure to LPS caused an intense inflammatory response and apoptosis in both A549 and BEAS-2B cells. DTA0118 treatment downregulated Toll-like receptor-4 expression and upregulated nuclear factor-kappaB inhibitor-alpha expression in cells exposed to LPS. These anti inflammatory effects were accompanied by a significantly lower secretion of interleukin-6 (IL-6), IL-8, and IL-1beta. The observed antiapoptotic effect of DTA0118 was associated with the upregulation of antiapoptotic Bcl-2 and downregulation of proapoptotic Bax and active caspase-3 protein levels. Our findings demonstrate the potent anti-inflammatory and antiapoptotic properties of the pyrrol DTA0118 compound and suggest that it could be considered as a potential drug therapy for the acute phase of sepsis and septic ARDS. Further investigations are needed to examine and validate these mechanisms and effects in a clinically relevant animal model of sepsis and sepsis-induced ARDS. PMID- 26999660 TI - Effects of combination PPARgamma agonist and angiotensin receptor blocker on glomerulosclerosis. AB - We previously observed that high-dose angiotensin receptor blocker (ARB) can induce regression of existing glomerulosclerosis. We also found that proliferator activated recepto-gamma (PPARgamma) agonist can attenuate glomerulosclerosis in a nondiabetic model of kidney disease, with specific protection of podocytes. We now assessed effects of combination therapy with ARB and pioglitazone on established glomerulosclerosis. Sprague-Dawley male rats underwent 5/6 nephrectomy (5/6 Nx) at week 0 and renal biopsy at week 8. Rats were randomized to groups with equal starting moderate glomerulosclerosis, and treated with ARB, PPARgamma agonist (pioglitazone), combination or vehicle from weeks 8 to 12. Body weight, systolic blood pressure (SBP), and urinary protein (UP) were measured at intervals. In rats with established sclerosis, SBP, UP, and GS were equal in all groups at week 8 before treatment by study design. Untreated control rats had hypertension, decreased GFR, and progressive proteinuria and glomerulosclerosis at week 12. Only combination therapy significantly ameliorated hypertension and proteinuria. ARB alone or pioglitazone alone had only numerically lower SBP and UP than vehicle at week 12. Both pioglitazone alone and combination had significantly less decline in GFR than vehicle. Combination-induced regression of glomerulosclerosis in more rats from weeks 8 to 12 than ARB or pioglitazone alone. In parallel, combination treatment reduced plasminogen activator inhibitor 1 expression and macrophage infiltration, and preserved podocytes compared with vehicle. These results were linked to increased AT2 receptor and Mas1 mRNA in the combination group. PPARgamma agonists in combination with ARB augment regression of glomerulosclerosis, with downregulation of injurious RAAS components vs PPARgamma alone, with increased anti-fibrotic/healing RAAS components, enhanced podocyte preservation, and decreased inflammation and profibrotic mechanisms. PMID- 26999662 TI - Influence of Resource Availability on the Foraging Strategies of the Triangle Butterflyfish Chaetodon triangulum in the Maldives. AB - Obligate coral feeders such as many members of the Chaetodontidae family (also known as butterflyfish) often show strong preferences for particular coral species. This is thought to have evolved through natural selection as an energy maximising strategy. Although some species remain as highly specialised feeders throughout their lifetime, many corallivores show a degree of dietary versatility when food abundance is limited; a strategy described by the optimal foraging theory. This study aimed to examine if, within-reef differences in the feeding regime and territory size of the Triangle Butterflyfish Chaetodon triangulum occurred, as a function of resource availability. Results showed that the dietary specialisation of C. triangulum was significant in both areas of low and high coral cover (chiL22 = 2.52 x 102, P<0.001 and chiL22 = 3.78 x 102, P<0.001 respectively). Resource selection functions (RSFs), calculated for the two main sites of contrasting coral assemblage, showed that in the resource-rich environments, only two Genera (Acropora and Pocillopora) were preferentially selected for, with the majority of other corals being actively 'avoided'. Conversely, in territories of lower coral coverage, C. triangulum was being less selective in its prey choice and consuming corals in a more even distribution with respect to their availability. Interestingly, coral cover appeared to show no significant effect on feeding rate, however it was a primary determinant of territory size. The findings of the study agree with the predictions of the optimal foraging theory, in that where food supply is scarce, dietary specialisation is minimised and territory size increased. This results in maximising energy intake. This study represents the first scientific evidence that C. triangulum is an obligate corallivore and, as with many other butterflyfish, is therefore dependent on healthy scleractinian corals for survival. PMID- 26999663 TI - 1,25-Dihydroxyvitamin D3 Facilitates M2 Polarization and Upregulates TLR10 Expression on Human Microglial Cells. AB - OBJECTIVE: To explore the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D, on M1/M2 polarization of human microglia and the expression of Toll-like receptor 10 (TLR10) on these cells, which has been suggested to play an inhibitory role in inflammation previously. METHODS: Microglial HMO6 cells were treated with 1,25(OH)2D3, and mRNA or protein levels of M1 and M2 cytokines and TLR10 were examined. RESULTS: 1,25(OH)2D3 upregulated TLR10 in HMO6 cells at both mRNA and protein level. 1,25(OH)2D3 enhanced basal mRNA expression of M2 cytokines, such as IL-10 and CCL17, but did not affect the expression of M1 cytokines, including IL-12 and TNF-alpha. 1,25(OH)2D3 downregulated the lipopolysaccharide (LPS)-induced mRNA expression of M1 cytokines IL-12 and TNF-alpha. Concomitantly, it upregulated not only the M2 cytokines IL-10 and CCL17, but also TLR10 in microglial cells treated with LPS, in a concentration-dependent manner. CONCLUSIONS: Our results suggest that 1,25(OH)2D3 may exert anti-inflammatory action by facilitating the M2 polarization of human microglial cells. PMID- 26999661 TI - Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress induced podocyte apoptosis in diabetic nephropathy. AB - Endoplasmic reticulum (ER) stress, resulting from the accumulation of misfolded and/or unfolded proteins in ER membranes, is involved in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to investigate the role of ER stress inhibitors ursodeoxycholic acid (UDCA) and 4-phenylbutyrate (4-PBA) in the treatment of DN in db/db mice. Findings have revealed that diabetic db/db mice were more hyperglycemic than their non-diabetic controls, and exhibited a marked increase in body weight, water intake, urine volume, fasting plasma glucose, systolic blood pressure, glucose and insulin tolerance. UDCA (40 mg/kg/day) or 4-PBA (100 mg/kg/day) treatment for 12 weeks resulted in an improvement in these biochemical and physical parameters. Moreover, UDCA or 4-PBA intervention markedly decreased urinary albuminuria and attenuated mesangial expansion in diabetic db/db mice, compared with db/db mice treated with vehicle. These beneficial effects of UDCA or 4-PBA on DN were associated with the inhibition of ER stress, as evidenced by the decreased expression of BiP, phospho IRE1alpha, phospho-eIF2alpha, CHOP, ATF-6 and spliced X-box binding protein-1 in vitro and in vivo. UDCA or 4-PBA prevented hyperglycemia-induced or high glucose (HG)-induced apoptosis in podocytes in vivo and in vitro via the inhibition of caspase-3 and caspase-12 activation. Autophagy deficiency was also seen in glomeruli in diabetic mice and HG-incubated podocytes, exhibiting decreased expression of LC3B and Beclin-1, which could be restored by UDCA or 4-PBA treatment. Taken together, our results have revealed an important role of ER stress in the development of DN, and UDCA or 4-PBA treatment may be a potential novel therapeutic approach for the treatment of DN. PMID- 26999664 TI - Molecular Evolution and Spatial Transmission of Severe Fever with Thrombocytopenia Syndrome Virus Based on Complete Genome Sequences. AB - Severe fever with thrombocytopenia syndrome virus (SFTSV) was a novel tick-borne bunyavirus that caused hemorrhagic fever with a high fatality rate in East Asia. In this study we analyzed the complete genome sequences of 122 SFTSV strains to determine the phylogeny, evolution and reassortment of the virus. We revealed that the evolutionary rate of three genome segments were different, with highest in the S segment and lowest in the L segment. The SFTSV strains were phylogenetically classified into 5 lineages (A, B, C, D and E) with each genome segment. SFTSV strains from China were classified in all 5 lineages, strains from South Korea were classified into 3 lineages (A, D, and E), and all strains from Japan were classified in only linage E. Using the average evolutionary rate of the three genome segments, we found that the extant SFTSV originated 20-87 years ago in the Dabie Mountain area in central China. The viruses were then transmitted to other areas of China, Japan and South Korea. We also found that six SFTSV strains were reassortants. Selection pressure analysis suggested that SFTSV was under purifying selection according to the four genes (RNA-dependent RNA polymerase, glycoprotein, nucleocapsid protein, non-structural protein), and two sites (37, 1033) of glycoproteins were identified as being under strong positive selection. We concluded that SFTSV originated in central China and spread to other places recently and the virus was under purifying selection with high frequency of reassortment. PMID- 26999665 TI - Corticospinal and Reticulospinal Contacts on Cervical Commissural and Long Descending Propriospinal Neurons in the Adult Rat Spinal Cord; Evidence for Powerful Reticulospinal Connections. AB - Descending systems have a crucial role in the selection of motor output patterns by influencing the activity of interneuronal networks in the spinal cord. Commissural interneurons that project to the contralateral grey matter are key components of such networks as they coordinate left-right motor activity of fore and hind-limbs. The aim of this study was to determine if corticospinal (CST) and reticulospinal (RST) neurons make significant numbers of axonal contacts with cervical commissural interneurons. Two classes of commissural neurons were analysed: 1) local commissural interneurons (LCINs) in segments C4-5; 2) long descending propriospinal neurons (LDPNs) projecting from C4 to the rostral lumbar cord. Commissural interneurons were labelled with Fluorogold and CST and RST axons were labelled by injecting the b subunit of cholera toxin in the forelimb area of the primary somatosensory cortex or the medial longitudinal fasciculus respectively. The results show that LCINs and LDPNs receive few contacts from CST terminals but large numbers of contacts are formed by RST terminals. Use of vesicular glutamate and vesicular GABA transporters revealed that both types of cell received about 80% excitatory and 20% inhibitory RST contacts. Therefore the CST appears to have a minimal influence on LCINs and LDPNs but the RST has a powerful influence. This suggests that left-right activity in the rat spinal cord is not influenced directly via CST systems but is strongly controlled by the RST pathway. Many RST neurons have monosynaptic input from corticobulbar pathways therefore this pathway may provide an indirect route from the cortex to commissural systems. The cortico-reticulospinal-commissural system may also contribute to functional recovery following damage to the CST as it has the capacity to deliver information from the cortex to the spinal cord in the absence of direct CST input. PMID- 26999667 TI - Dietary Fatty Acids Differentially Associate with Fasting Versus 2-Hour Glucose Homeostasis: Implications for The Management of Subtypes of Prediabetes. AB - Over-nutrition has fuelled the global epidemic of type 2 diabetes, but the role of individual macronutrients to the diabetogenic process is not well delineated. We aimed to examine the impact of dietary fatty acid intake on fasting and 2-hour plasma glucose concentrations, as well as tissue-specific insulin action governing each. Normoglycemic controls (n = 15), athletes (n = 14), and obese (n = 23), as well as people with prediabetes (n = 10) and type 2 diabetes (n = 11), were queried about their habitual diet using a Food Frequency Questionnaire. All subjects were screened by an oral glucose tolerance test (OGTT) and studied using the hyperinsulinemic/euglycemic clamp with infusion of 6,62H2-glucose. Multiple regression was performed to examine relationships between dietary fat intake and 1) fasting plasma glucose, 2) % suppression of endogenous glucose production, 3) 2-hour post-OGTT plasma glucose, and 4) skeletal muscle insulin sensitivity (glucose rate of disappearance (Rd) and non-oxidative glucose disposal (NOGD)). The %kcal from saturated fat (SFA) was positively associated with fasting (beta = 0.303, P = 0.018) and 2-hour plasma glucose (beta = 0.415, P<0.001), and negatively related to % suppression of hepatic glucose production (beta = -0.245, P = 0.049), clamp Rd (beta = -0.256, P = 0.001) and NOGD (beta = -0.257, P = 0.001). The %kcal from trans fat was also negatively related to clamp Rd (beta = 0.209, P = 0.008) and NOGD (beta = -0.210, P = 0.008). In contrast, the %kcal from polyunsaturated fat (PUFA) was negatively associated with 2-hour glucose levels (beta = -0.383, P = 0.001), and positively related to Rd (beta = 0.253, P = 0.007) and NOGD (beta = 0.246, P = 0.008). Dietary advice to prevent diabetes should consider the underlying pathophysiology of the prediabetic state. PMID- 26999669 TI - Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas. AB - The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind (99m)Tc. The radiolabeled complex, (99m)Tc (EST)2DT was obtained in >99% radiochemical purity and 20-48 GBq/MUmol of specific activity. RBA assay revealed ~15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ~6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(-) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 MUM which was comparable to tamoxifen. The anticancer activity of the ligand is possibly due to the increase in ERbeta and suppression of ERalpha protein levels in gene transcription. The studies reveal the potential of (EST)2DT as diagnostic imaging agent with the additional benefits in therapy. PMID- 26999670 TI - Nondisclosure of Complementary and Alternative Medicine Use to Primary Care Physicians: Findings From the 2012 National Health Interview Survey. PMID- 26999666 TI - Functional and Biochemical Characterization of Alvinella pompejana Cys-Loop Receptor Homologues. AB - Cys-loop receptors are membrane spanning ligand-gated ion channels involved in fast excitatory and inhibitory neurotransmission. Three-dimensional structures of these ion channels, determined by X-ray crystallography or electron microscopy, have revealed valuable information regarding the molecular mechanisms underlying ligand recognition, channel gating and ion conductance. To extend and validate the current insights, we here present promising candidates for further structural studies. We report the biochemical and functional characterization of Cys-loop receptor homologues identified in the proteome of Alvinella pompejana, an extremophilic, polychaete annelid found in hydrothermal vents at the bottom of the Pacific Ocean. Seven homologues were selected, named Alpo1-7. Five of them, Alpo2-6, were unidentified prior to this study. Two-electrode voltage clamp experiments revealed that wild type Alpo5 and Alpo6, both sharing remarkably high sequence identity with human glycine receptor alpha subunits, are anion-selective channels that can be activated by glycine, GABA and taurine. Furthermore, upon expression in insect cells fluorescence size-exclusion chromatography experiments indicated that four homologues, Alpo1, Alpo4, Alpo6 and Alpo7, can be extracted out of the membrane by a wide variety of detergents while maintaining their oligomeric state. Finally, large-scale purification efforts of Alpo1, Alpo4 and Alpo6 resulted in milligram amounts of biochemically stable and monodisperse protein. Overall, our results establish the evolutionary conservation of glycine receptors in annelids and pave the way for future structural studies. PMID- 26999672 TI - Serotonin receptor 2C regulates neurite growth and is necessary for normal retinal processing of visual information. AB - Serotonin (5HT) is present in a subpopulation of amacrine cells, which form synapses with retinal ganglion cells (RGCs), but little is known about the physiological role of retinal serotonergic circuitry. We found that the 5HT receptor 2C (5HTR2C) is upregulated in RGCs after birth. Amacrine cells generate 5HT and about half of RGCs respond to 5HTR2C agonism with calcium elevation. We found that there are on average 83 5HT+ amacrine cells randomly distributed across the adult mouse retina, all negative for choline acetyltransferase and 90% positive for tyrosine hydroxylase. We also investigated whether 5HTR2C and 5HTR5A affect RGC neurite growth. We found that both suppress neurite growth, and that RGCs from the 5HTR2C knockout (KO) mice grow longer neurites. Furthermore, 5HTR2C is subject to post-transcriptional editing, and we found that only the edited isoform's suppressive effect on neurite growth could be reversed by a 5HTR2C inverse agonist. Next, we investigated the physiological role of 5HTR2C in the retina, and found that 5HTR2C KO mice showed increased amplitude on pattern electroretinogram. Finally, RGC transcriptional profiling and pathways analysis suggested partial developmental compensation for 5HTR2C absence. Taken together, our findings demonstrate that 5HTR2C regulates neurite growth and RGC activity and is necessary for normal amplitude of RGC response to physiologic stimuli, and raise the hypothesis that these functions are modulated by a subset of 5HT+/ChAT /TH+ amacrine cells as part of retinal serotonergic circuitry. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017. PMID- 26999671 TI - Functional activation of PPARgamma in human upper aerodigestive cancer cell lines. AB - Upper aerodigestive cancer is an aggressive malignancy with relatively stagnant long-term survival rates over 20 yr. Recent studies have demonstrated that exploitation of PPARgamma pathways may be a novel therapy for cancer and its prevention. We tested whether PPARgamma is expressed and inducible in aerodigestive carcinoma cells and whether it is present in human upper aerodigestive tumors. Human oral cancer CA-9-22 and NA cell lines were treated with the PPAR activators eicosatetraynoic acid (ETYA), 15-deoxy-delta- 12,14 prostaglandin J2 (PG-J2), and the thiazolidinedione, ciglitazone, and evaluated for their ability to functionally activate PPARgamma luciferase reporter gene constructs. Cellular proliferation and clonogenic potential after PPARgamma ligand treatment were also evaluated. Aerodigestive cancer specimens and normal tissues were evaluated for PPARgamma expression on gene expression profiling and immunoblotting. Functional activation of PPARgamma reporter gene constructs and increases in PPARgamma protein were confirmed in the nuclear compartment after PPARgamma ligand treatment. Significant decreases in cell proliferation and clonogenic potential resulted from treatment. Lipid accumulation was induced by PPARgamma activator treatment. 75% of tumor specimens and 100% of normal control tissues expressed PPARgamma RNA, and PPARgamma protein was confirmed in 66% of tumor specimens analyzed by immunoblotting. We conclude PPARgamma can be functionally activated in upper aerodigestive cancer and that its activation downregulates several features of the neoplastic phenotype. PPARgamma expression in human upper aerodigestive tract tumors and normal cells potentially legitimizes it as a novel intervention target in this disease. (c) 2016 Wiley Periodicals, Inc. PMID- 26999673 TI - In vitro investigation of molecules involved in Lactobacillus gasseri SBT2055 adhesion to host intestinal tract components. AB - AIMS: The adhesion ability of Lactobacillus gasseri SBT2055 was investigated in vitro by searching for its adhesion molecules. METHODS AND RESULTS: Lactobacillus gasseri SBT2055 showed adherence to host components, including two commercially available mucins, Caco-2 epithelial-like cells and the extracellular matrix molecule fibronectin (Fn). Its adhesion rates to host components were generally higher than those of other Lactobacillus strains. We examined sortase-dependent proteins (SDPs) anchored by a sortase enzyme encoded by srtA1. The adhesion rates of an srtA1 disruptant were lower than those of Lact. gasseri SBT2055, and the relative adherences were as follows: two mucins, 43 and 40%; Caco-2, 66% and Fn, 28%. Seven additional gene disruptants were generated to determine the precise SDPs that contribute to adhesion to each component. CONCLUSIONS: The adhesion ability of Lact. gasseri SBT2055 was superior to those of other Lactobacillus strains. Additionally, four adhesion molecules were newly identified from candidate SDPs. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the contribution of SDPs to adhesion has been reported using sortase gene disruptants, this is the first report to identify the precise SDPs that act as adhesion molecules. Our results will contribute to achieving better understanding of probiotic bacterial adherence. PMID- 26999674 TI - The Role of Parieto-Occipital Junction in the Interaction between Dorsal and Ventral Streams in Disparity-Defined Near and Far Space Processing. AB - Neuropsychological and functional MRI data suggest that two functionally and anatomically dissociable streams of visual processing exist: a ventral perception related stream and a dorsal action-related stream. However, relatively little is known about how the two streams interact in the intact brain during the production of adaptive behavior. Using functional MRI and a virtual three dimensional paradigm, we aimed at examining whether the parieto-occipital junction (POJ) acts as an interface for the integration and processing of information between the dorsal and ventral streams in the near and far space processing. Virtual reality three-dimensional near and far space was defined by manipulating binocular disparity, with -68.76 arcmin crossed disparity for near space and +68.76 arcmin uncrossed disparity for near space. Our results showed that the POJ and bilateral superior occipital gyrus (SOG) showed relative increased activity when responded to targets presented in the near space than in the far space, which was independent of the retinotopic and perceived sizes of target. Furthermore, the POJ showed the enhanced functional connectivity with both the dorsal and ventral streams during the far space processing irrespective of target sizes, supporting that the POJ acts as an interface between the dorsal and ventral streams in disparity-defined near and far space processing. In contrast, the bilateral SOG showed the enhanced functional connectivity only with the ventral stream if retinotopic sizes of targets in the near and far spaces were matched, which suggested there was a functional dissociation between the POJ and bilateral SOG. PMID- 26999675 TI - Proteomic and metabolomic analysis on the toxicological effects of Benzo[a]pyrene in pearl oyster Pinctada martensii. AB - Benzo[a]pyrene (BaP) is one of the typical toxic polycyclic aromatic hydrocarbons (PAHs) that are widely present in marine environment. BaP has diverse toxic effects, including teratogenic, carcinogenic, mutagenic effects and so on, in various organisms. In this work, we focused on the differential proteomic and metabolomic responses in the digestive gland of pearl oyster Pinctada martensii exposed to two doses of BaP (1 and 10MUg/L). Metabolic responses revealed that the high dose of BaP (10MUg/L) mainly caused disturbances in osmotic regulation and energy metabolism in the digestive gland. Proteomic responses indicated that both doses of BaP induced disturbances in energy metabolism, cytoskeleton, cell injury, oxidative stress and signal transduction based on the differential proteomic biomarkers. Overall, these results demonstrated a number of potential biomarkers that were characterized by an integrated proteomic and metabolomic approach and provided a useful insight into the toxicological effects on pearl oyster P. martensii. PMID- 26999676 TI - The Mitral Valve Meeting in Zurich - a world upside down. PMID- 26999677 TI - Oversized post-dilatation of current bioresorbable vascular scaffolds: kill or cure? PMID- 26999679 TI - Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) fails to solve the haemodynamic support equation in cardiogenic shock. PMID- 26999678 TI - Bioresorbable scaffolds for calcified lesions: not a free lunch! PMID- 26999680 TI - Long-term prognosis after extracorporeal life support in refractory cardiogenic shock: results from a real-world cohort. AB - AIMS: The current study presents data from a real-world cohort of patients with refractory cardiogenic shock (CS) undergoing extracorporeal life support (ECLS) with the aims of reporting clinical experience, objectifying complications as well as survival, and identifying predictors of mortality. METHODS AND RESULTS: Eighty-three patients with refractory CS underwent percutaneous ECLS implantation performed by interventional cardiologists. Follow-up was performed at hospital discharge as well as at 18 months (IQR 15-36). Good clinical outcome was defined as survival with a Cerebral Performance Category (CPC) of 1-2. Median age was 61 years (IQR 50-72) and cardiopulmonary resuscitation prior to ECLS implantation was performed in 46 patients (55.4%). Aetiologies of CS were acute myocardial infarction (63.9%), acute deterioration of ischaemic cardiomyopathy (6.0%) or non ischaemic acute heart failure (16.9%), valvular heart disease (9.6%), and interventional complications (3.6%). Although initial ECLS weaning was successful in 47 patients (56.6%), in-hospital mortality was 68.7%. Of all 83 patients initially undergoing ECLS implantation, only 15 patients (18.1%) were alive at follow-up, 13 (15.7%) with a CPC of 1-2. Age was identified as an independent predictor of mortality (p=0.04). CONCLUSIONS: Despite ECLS support, the long-term prognosis of patients with CS refractory to standard treatment remains poor. PMID- 26999683 TI - Transapical valve-in-valve TAVI in a patient with two failing surgical bioprostheses with Edwards SAPIEN 3 valves using a cerebral protection system. PMID- 26999682 TI - Computed tomography optimised fluoroscopy guidance for transcatheter mitral therapies. AB - AIMS: Our aim was to illustrate the pragmatic use of pre-procedural multislice computed tomography (MSCT) to facilitate fluoroscopy guidance of transcatheter mitral valve interventions. METHODS AND RESULTS: A dedicated software package (3mensio Structural Heart) is used to analyse MSCT studies and localise anatomical entities by fluoroscopy which would otherwise be invisible (e.g., interatrial septum, paravalvular leaks, mitral leaflets), and to provide optimal C-arm gantry angles to facilitate crucial steps of catheter-based mitral interventions. For any given anatomical structure that has been identified by MSCT scan, a line of perpendicularity can be drawn representing an infinite combination of RAO-LAO with cranial-caudal angles. Safety and ergonomic considerations drive the selected angulation to be used in the cathlab. The location of the fossa ovalis can be projected onto the fluoroscopy screen to help direct the needle for transseptal puncture. For MitraClip implantations a C-arm gantry projection that is either coaxial or perpendicular to the mitral coaptation plane helps to orientate the clip before entering the left ventricle to grasp the mitral leaflets. A periprosthetic mitral leak can be localised relative to the prosthesis in the proposed C-arm angle. Pre-procedural MSCT is thus complementary to transoesophageal echocardiography for transcatheter mitral interventions. CONCLUSIONS: Determination of optimal C-arm angulations helps localise anatomical entities by fluoro-scopy and may expedite complex mitral interventions. PMID- 26999681 TI - Video densitometric assessment of aortic regurgitation after transcatheter aortic valve implantation: results from the Brazilian TAVI registry. AB - AIMS: We sought to examine the feasibility and reproducibility of a new video densitometric (VD) quantification of aortic regurgitation (AR) on aortography, and its long-term clinical impact. METHODS AND RESULTS: Using dedicated video densitometry software, AR after TAVI was quantified, and inter- and intra observer reproducibility was investigated in 182 aortograms of the Brazilian TAVI registry. The aortograms were analysed using two software algorithms: 1) the quantitative regurgitation analysis (qRA) index interrogating the entire left ventricle (LV), and 2) a new method with the left ventricle outflow tract (LVOT) as a region of interest (ROI) (LVOT-AR). LVOT-AR was feasible in 64.8% vs. 29.7% of aortograms, compared with qRA index. Using the LVOT-AR, inter-observer variability was low (mean difference+/-standard deviation [SD]: 0.01+/-0.05, p=0.53), and the two observers' measurements were highly correlated (r=0.95, p<0.001). Patients with LVOT-AR >0.17 had a significantly higher one-year all cause mortality risk compared with patients with LVOT-AR <=0.17 (37.1% vs. 11.2%, p=0.0008). CONCLUSIONS: This study proposes an alternative methodology for AR assessment after TAVI by using the LVOT method (LVOT-AR) of VD angiography. The assessment of LVOT-AR is feasible, reproducible and potentially predictive of one year mortality. PMID- 26999684 TI - How should I treat a left ventricular outflow tract-migrated balloon-expandable transcatheter heart valve? PMID- 26999686 TI - Bioresorbable vascular scaffolds for recurrent in-stent restenosis. PMID- 26999685 TI - Recurrent in-stent restenosis: many treatment options, no certainty. PMID- 26999687 TI - The COMT Val158Met polymorphism moderates the association between cognitive functions and white matter microstructure in schizophrenia. AB - OBJECTIVES: Impaired cognitive functioning is a core feature of schizophrenia. Cognitive impairment in schizophrenia has been associated with white-matter (WM) abnormalities and degenerative changes of cortical myelin in the cerebral cortex. Furthermore, findings suggested a role of the COMT gene in affecting both WM and neuropsychological performances.We thus hypothesized that the COMT ValMet genotype would affect the association between cognitive functions and WM microstructure in a sample of schizophrenic patients. MATERIALS AND METHODS: Seventy-eight schizophrenic patients performed the brief assessment of cognition in schizophrenia for assessment of cognitive performances. Sixty-nine patients provided a venous blood sample for genotypic analysis. WM integrity was evaluated using tract-based spatial statistics with threshold-free cluster enhancement (P<0.05). RESULTS: Analysis indicated an association between cognitive functions and WM microstructure in the Val/Val group, but not in the Met carriers group. WM tracts include the corpus callosum, thalamic radiations, corona radiata, forceps major and minor, superior and inferior longitudinal fasciculus, inferior fronto occipital fasciculus, corticospinal tract, and cingulum. CONCLUSION: Results suggested a moderating effect of the COMT ValMet polymorphism on the association between cognitive functioning and WM microstructure. Our findings support the importance of myelination in cognition, identifying measures of WM microstructure as important neurobiological features of cognitive performances. PMID- 26999689 TI - Cerebrospinal fluid ferritin and albumin index: potential candidates for scoring system to differentiate between bacterial and viral meningitis in children. AB - OBJECTIVES: To evaluate the diagnostic role of cerebrospinal fluid (CSF) ferritin and albumin index (AI = CSF albumin/serum albumin * 1000) in differentiating acute bacterial meningitis (ABM) from acute viral meningitis (AVM) in children. METHODS: The study included 42 cases each of ABM and AVM in pediatric age group. Receiver operating characteristic (ROC) analysis was carried out for CSF ferritin and AI. Binary logistic regression was also done. RESULTS: CSF ferritin and AI were found significantly higher in ABM compared to AVM. Model obtained using AI and CSF ferritin along with conventional criteria is better than existing models. PMID- 26999688 TI - Role of antioxidants in gestational diabetes mellitus and relation to fetal outcome: a randomized controlled trial. AB - OBJECTIVE: To examine the effect of antioxidant administration on the oxidative parameters in both blood and placental tissue and its relation to fetal outcome in women with GDM. PATIENTS AND METHODS: Two-hundred pregnant women with gestational diabetes mellitus (GDM) were randomized into 2 groups, Group1 received 1 gram L-ascorbic acid per day and Group2 received placebo. RESULTS: The use of antioxidants significantly lower the needed insulin dose for blood sugar control (25.6 +/- 20.3 versus 40.5 +/- 23.7, respectively). In placental tissue homogenates, glutathione (GSH) was 49.6 +/- 5.9 versus 62.34 +/- 4.99, malondialdahyde (MDA) was 165.7 +/- 9.2 versus 264.15 +/- 12, superoxide dismutase (SOD) was 0.3 +/- 0.3 versus 0.054 +/- 0.16 while catalase (CAT) was 14.06 +/- 2.4 versus 15.52 +/- 3.97 and glutathione peroxidase (GPx) was 14 +/- 4.1 versus 26.3 +/- 4.26 in antioxidant group compared to the control group (p < 0.001). In maternal blood, GSH was 1.5 +/- 0.3 versus 0.74 +/- 0.088, CAT was 380.7 +/- 11 versus 325.44 +/- 21.8, GPx was 52.3 +/- 8.7 versus 75.82 +/- 6.84 and SOD was 188 +/- 15.3 versus 98.56 +/- 11.05 in antioxidant group compared to control group (p < 0.001). In neonatal blood, the level of MDA and SOD showed a statistically significant difference between antioxidants and control groups (4 +/- 0.7 versus 6.6 7 +/-0.66 and1 8 8 +/- 15.3 versus 98.5 +/- 11.05, respectively) (p < 0.001). The neonatal blood sugar after 1 and 2 hours of delivery was more stable in antioxidant group (56.7 +/- 10.9 versus 39.7 +/- 11.1 and 58.5 +/- 10.8 versus 41.7 +/- 13.1, respectively) (p <0.05). The neonates NICU admission was lower in antioxidant group (5 versus 11) (p <0.05). CONCLUSION: The use of antioxidants markedly reverses the oxidative stresses in women with GDM with marked improvement on neonatal outcome. PMID- 26999690 TI - We should not use oxybutynin chloride in OAB. PMID- 26999691 TI - Stress Analysis of Axial and Tilted Implants in Full-arch Fixed Dentures Under Different Abutment Conditions. AB - The aim of this study was to evaluate the stress distribution on full-arch prostheses, considering axial implants and tilted implants with or without abutments. Two photoelastic models were made, being that in 1 model the implants were inserted perpendicular, whereas in the other model 2 implants were inserted perpendicular and 2 implants were inserted with tilting 30 degrees to the distal area. The prosthetic situations were evaluated: A-axial implants and nonsegmented full-arch prosthesis; B-axial implants and segmented full-arch prosthesis; C tilted distal implants and nonsegmented full-arch prosthesis; D-tilted distal implants and segmented full-arch prosthesis, and was applied an axial load of 100 N at 5 points. The results showed greater stress concentration for axial implants than tilted implants in anterior and posterior loading. There was no difference in stress distribution to the use of abutment in the tilted implants. Shorter cantilever with tilted implants improved the stress distribution; the use of abutment did not influence the stress distribution. PMID- 26999692 TI - Primary Occipital Encephalocele in an Elderly Patient. AB - The encephalocele is a condition characterized by the protrusion of the intracranial contents through a bone defect of the skull. The authors report a clinical case of an 80-year-old woman with primary occipital encephalocele on the right side and that was affected by trauma and presented liquor fistula and infection. Tomographic sections were obtained by injection intravenous of contrast. The images showed bone thickness thinning on the right occipital region and solution of continuity (encephalocele) with regular contours, reduction in brain volume, and hypodensity of the periventricular white substance were observed. The patient was successfully operated. PMID- 26999693 TI - Management of Limited Vertical Bone Height in the Posterior Mandible: Short Dental Implants Versus Nerve Lateralization With Standard Length Implants. AB - Inferior alveolar nerve lateralization (IANL) and short dental implants (SDI) are 2 viable implant-based treatment approaches in the presence of atrophied posterior mandible. Despite the risks of dysfunction, infection, and pathologic fractures in IANL, it becomes possible to place standard implants. The purpose of this study was to compare SDI and IANL approaches from clinical and radiographic aspects. Fifteen subjects having unilateral atrophic mandibles were allocated to SDI and IANL treatment groups. Following surgical procedures, early postoperative complications, implant survival, and periimplant clinical and radiographic parameters including probing pocket depth, attachment level, keratinized tissue amount, vertical tissue recession, and marginal bone loss were recorded at baseline and 1-year after prosthetic rehabilitation. In both groups, no implant was lost. Except usual postoperative complications, 2 patients had transient paraesthesia after IANL. According to time-dependent evaluation, both groups showed significant increase in probing pocket depth and attachment level at 1 year follow-up compared with baseline (P < 0.05). Except a slight but significant increase in mesial surface of SDI group (P < 0.05), no remarkable time-dependent change was identified in vertical tissue recession. Keratinized tissue amount did not exhibit any inter- or intragroup difference during whole study period. Marginal bone loss did not show any difference between IANL and SDI groups at follow-up. SDI placement or standard length implant placement with IANL can be considered promising alternatives in the treatment of atrophic mandibular posterior regions. However, SDI may be preferred in terms of lower complication risk. PMID- 26999694 TI - Versatility of Distraction Osteogenesis for the Craniofacial Skeleton. AB - Malformations of the craniofacial skeleton are common. Restoration of anatomic shape, size, and position has been traditionally accomplished using autologous bone grafting to fill gaps created by surgery and segmental movement. The authors present their practice using distraction in many different ages and settings over 20 years. A retrospective review was performed of all craniofacial patients treated using distraction osteogenesis for mandible, midface, and calvarium. The authors identified 205 patient. Mandible: 112 patients were treated at an average age of 3.4 years. 18.8% of patients required repeat distraction. There was no difference in the neonatal versus older group (P = 0.71). There were significantly higher reoperation rates in syndromic children (P < 0.01). Midface: 58 patients underwent Lefort III distraction at an average age of 13.6 years. One (1.7%) required repeat distraction (Miller syndrome). Five (8.6%) patients underwent subsequent Lefort I advancement for occlusal changes. Calvarium: 33 patients were treated at an average age of 4.7 years. No repeat distractions were performed. One patient required an additional advancement procedure. Distraction demonstrates successful long-term correction of defects in the craniofacial skeleton with the versatility and control needed to treat the wide spectrum of deformity. PMID- 26999695 TI - Intranasal Extramucosal Access: A New Access for Lateral Osteotomy in Open Rhinoplasty. AB - BACKGROUND AND OBJECTIVE: Different accesses have been used to perform lateral osteotomies in rhinoplasty. All of them have some disadvantages. The aim of this paper was to report a new access to overcome drawbacks of the other techniques in lateral osteotomy during open rhinoplasty. METHODS: An anatomical study was designed to search possibility of intranasal extramucosal access (open sky access) for the lateral osteotomy in open rhinoplasty. It was performed directly on the lateral wall of piriform aperture, and then possible advantages of this technique were investigated. Five fixed cadavers were used for this purpose. No drawbacks were observed during procedure in cadavers. Then the same procedure was performed in 23 consecutive rhinoplasty patients. Nineteen operations were primary and 4 operations were secondary. Median oblique osteotomies were added to the procedure in all patients. The mean follow-up was 17 months. RESULTS: Intranasal extramucosal access during lateral osteotomy was easily performed in all patients. Hemorrhage due to angular vessel injury was not occurred during intraoperative period. Edema and ecchymosis was minimal. Intranasal examination did not show any sign for nasal mucosal tearing in all patients. Residual bone spurs or bone irregularities were not observed in any patients. CONCLUSION: Intranasal extramucosal access that produces precise, predictable, and reproducible aesthetic and functional results could also provide better exposure during lateral osteotomy. Additionally, open sky access minimizes scars because it does not need additional incisions on the skin and mucosa. Protection of the internal periosteum of the nasal bones may be the main advantages of this technique. PMID- 26999697 TI - Eosinophilic Granuloma of the Mandible: Is a Conservative Treatment Sufficient for Local Disease Control? AB - Eosinophilic granuloma is the most benign and common form of the Langerhans cell histiocytosis, a rare proliferative disease that can affect single or multiple organs. In the quite common head and neck manifestation these lesions can be confused in the beginning, with other bone diseases such as odontogenic cysts, periodontal disease, or malignancies. Treatment varies depending on the size, number, localization of the lesions, and patient's general conditions. The authors describe here a patient of a single lesion of eosinophilic granuloma localized in the posterior mandible region treated with a very conservative surgical approach in a patient with poor socio-economic conditions. The authors performed teeth extractions, an excisional biopsy and open curettage and after a follow-up of 24 months without partial mandible resection and reconstruction time the lesion had healed. The clinical situation confirmed that, in carefully selective patients, a conservative approach could be a useful therapeutic opportunity. PMID- 26999696 TI - Huge Frontal-Temporal Lobe Arachnoid Cyst Presenting as an Weariness Migraine. AB - To the authors' knowledge, most of intracranial arachnoid cyst located in middle cranial fossa and lateral fissure cistern. So, huge frontal-temporal lobe arachnoid cyst is rare. Symptoms of arachnoid cyst may be atypical, including headache, nausea, vomiting, epilepsy, poor memory, and so on. Of course, migraine related to weariness is a rare benign headache disorder. The authors reported a patient presenting with weariness migraine associated with large frontal-temporal lobe arachnoid cyst. PMID- 26999700 TI - Giant Dermoid Cyst Causing Dysphagia and Dyspnea. AB - Dermoid cysts are benign lesions seen in young adults. The second most common localization is the floor of the mouth. They are usually asymptomatic over years but can be symptomatic due to secondary changes or the size. Herein, we report a case of 19-year-old woman who applied to emergency service with dyspnea, dysphagia and enlarging of a mass in the submental region. The patient cannot be entubated because of the mass pushing the tongue base backward closing the laryngeal view. Elective tracheostomy was performed for providing airflow during the operation. After the operation a cystic mass fulfilled with keratin lined by keratinized stratified squamous epithelium in addition to the dermal appendages such as sweat glands and follicular structures were seen histopathologically and the case was diagnosed as dermoid cyst of the submental region. In such patients with quick enlarging of mass causing airway obstructions, the tracheostomy can be the preferable method because of the difficulties in entubation. PMID- 26999701 TI - Contact stress analysis of the anterior tibial post in bi-cruciate stabilized and mobile-bearing posterior stabilized total knee arthroplasty designs. AB - In posterior-stabilized (PS) total knee arthroplasty (TKA), unexpected wear and fracture of the tibial post due to anterior post impingement have been reported. The purpose of this study was to determine the contact stress on the anterior aspect of the tibial post in four contemporary TKA designs. We evaluated one bi cruciate stabilized design (Journey II) and three mobile-bearing PS designs (Vanguard RP, PFC Sigma RP, and NexGen LPS Mobile). The contact conditions at the anterior aspect of the tibial post were determined upon application of a posterior force of 100N to individual implants. Each measurement was sequentially performed five times, and the data were compared within and across designs using analysis of variance and a post-hoc test. The contact stress of the Journey II and Vanguard RP was less than the compressive yield stress for polyethylene (10MPa) at all tested flexion angles and degrees of rotation. The PFC Sigma RP did not show anterior tibial post impingement under any experimental conditions. The NexGen LPS Mobile demonstrated bilateral edge loading at the anterior tibial post and exceeded 10MPa of contact stress in some test conditions. Thus, the differences among implants in terms of the dimensions of the femoral anterior cam or intercondylar notch and the anterior aspect of the tibial post in the axial and sagittal planes led to significant differences in contact conditions. The present study helps the surgeon to be more aware that various contact conditions of the anterior aspect of the tibial post can occur in individual TKA designs. PMID- 26999702 TI - Relationship between sample volumes and modulus of human vertebral trabecular bone in micro-finite element analysis. AB - Micro-finite element (MUFE) models have been widely used to assess the biomechanical properties of trabecular bone. How to choose a proper sample volume of trabecular bone, which could predict the real bone biomechanical properties and reduce the calculation time, was an interesting problem. Therefore, the purpose of this study was to investigate the relationship between different sample volumes and apparent elastic modulus (E) calculated from MUFE model. 5 Human lumbar vertebral bodies (L1-L5) were scanned by micro-CT. Cubic concentric samples of different lengths were constructed as the experimental groups and the largest possible volumes of interest (VOI) were constructed as the control group. A direct voxel-to-element approach was used to generate MUFE models and steel layers were added to the superior and inferior surface to mimic axial compression tests. A 1% axial strain was prescribed to the top surface of the model to obtain the E values. ANOVA tests were performed to compare the E values from the different VOIs against that of the control group. Nonlinear function curve fitting was performed to study the relationship between volumes and E values. The larger cubic VOI included more nodes and elements, and more CPU times were needed for calculations. E values showed a descending tendency as the length of cubic VOI decreased. When the volume of VOI was smaller than (7.34mm(3)), E values were significantly different from the control group. The fit function showed that E values approached an asymptotic values with increasing length of VOI. Our study demonstrated that apparent elastic modulus calculated from MUFE models were affected by the sample volumes. There was a descending tendency of E values as the length of cubic VOI decreased. Sample volume which was not smaller than (7.34mm(3)) was efficient enough and timesaving for the calculation of E. PMID- 26999703 TI - Zoledronic acid increases the circulating soluble RANKL level in mice, with a further increase in lymphocyte-derived soluble RANKL in zoledronic acid- and glucocorticoid-treated mice stimulated with bacterial lipopolysaccharide. AB - The nitrogen-containing bisphosphonate (BP) zoledronic acid (ZA) is a potent antiresorptive drug used in conjunction with standard cancer therapy to treat osteolysis or hypercalcemia due to malignancy. However, it is unclear how ZA influences the circulating levels of bone remodeling factors. The aim of this study was to evaluate the effects of ZA on the serum levels of soluble receptor activator of NF-kB ligand (sRANKL) and osteoprotegerin (OPG). The following four groups of C57BL/6 mice were used (five mice per group): (1) the placebo+phosphate buffered saline (PBS) group, in which placebo-treated mice were injected once weekly with PBS for 4weeks; (2) the placebo+ZA group, in which placebo-treated mice were injected once weekly with ZA for 4weeks; (3) the prednisolone (PSL)+PBS group, in which PSL-treated mice were injected once weekly with PBS for 4weeks; and (4) the PSL+ZA group, in which PSL-treated mice were injected once weekly with ZA for 4weeks. At the 3-week time point, all mice were subjected to oral inflammatory stimulation with bacterial lipopolysaccharide (LPS). The sera of these mice were obtained every week and the levels of sRANKL and OPG were measured using enzyme-linked immunosorbent assay. At the time of sacrifice, femurs were prepared for micro-computed tomography (micro-CT), histological, and histomorphometric analyses. Our data indicated that ZA administration remarkably reduced bone turnover and significantly increased the basal level of sRANKL. Interestingly, the PSL+ZA group showed a dramatically elevated sRANKL level after LPS stimulation. In contrast, the PSL+ZA group in nonobese diabetic mice with severe combined immunodeficiency disease (NOD-SCID mice), which are characterized by the absence of functional T- and B-lymphocytes, showed no increase in the sRANKL level. Our data suggest that, particularly with combination treatment of ZA and glucocorticoids, surviving lymphocytes might be the source of inflammation induced sRANKL. Thus, circulating sRANKL levels might be modulated by ZA. PMID- 26999704 TI - Perioperative kinetics of endocan in patients undergoing cardiac surgery with and without cardiopulmonary bypass. AB - INTRODUCTION: Endothelial Specific Molecule-1 or endocan is a novel biomarker associated with the development of acute lung injury (ALI) in response to a systemic inflammatory state such as trauma. Acute Respiratory Distress syndrome (ARDS), a severe form of ALI is a devastating complication that can occur following cardiac surgery due to risk factors such as the use of cardiopulmonary bypass (CPB) during surgery. In this study we examine the kinetics of endocan in the perioperative period in cardiac surgical patients. METHODS: After ethics approval, we obtained informed consent from 21 patients undergoing elective cardiac surgery (3 groups with seven patients in each group: coronary artery bypass grafting (CABG) with the use of CPB, off-pump CABG and complex cardiac surgery). Serial blood samples for endocan levels were taken in the perioperative period (T0: baseline prior to induction, T1: at the time of heparin administration, T2: at the time of protamine, T2, T3, T4 and T5 at 1, 2, 4 and 6h following protamine administration respectively). Endocan samples were analysed using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis incorporated the use of test for normality. RESULTS: Our results reveal that an initial rise in the levels of serum endocan from baseline in all patients after induction of anaesthesia. Patients undergoing off-pump surgery have lower endocan concentrations in the perioperative period than those undergoing CPB. Endocan levels decrease following separation from CPB, which may be attributed to haemodilution following CPB. Following administration of protamine, endocan concentrations steadily increased in all patients, reaching a steady state between 2 and 6h. The baseline endocan concentrations were elevated in patients with hypertension and severe coronary artery disease. CONCLUSION: Baseline endocan concentrations are higher in hypertensive patients with critical coronary artery stenosis. Endocan concentrations increased after induction of anaesthesia and decreased four hours after separation from CPB. Systemic inflammation may be responsible for the rise in endocan levels following CPB. PMID- 26999705 TI - Long-term reliability of ImPACT in professional ice hockey. AB - OBJECTIVE: This study sought to assess the test-retest reliability of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) across 2-4 year time intervals and evaluate the utility of a newly proposed two-factor (Speed/Memory) model of ImPACT across multiple language versions. METHOD: Test-retest data were collected from non-concussed National Hockey League (NHL) players across 2-, 3-, and 4-year time intervals. The two-factor model was examined using different language versions (English, French, Czech, Swedish) of the test using a one-year interval, and across 2-4 year intervals using the English version of the test. RESULTS: The two-factor Speed index improved reliability across multiple language versions of ImPACT. The Memory factor also improved but reliability remained below the traditional cutoff of .70 for use in clinical decision-making. ImPACT reliabilities remained low (below .70) regardless of whether the four-composite or the two-factor model was used across 2-, 3-, and 4-year time intervals. CONCLUSIONS: The two-factor approach increased ImPACT's one-year reliability over the traditional four-composite model among NHL players. The increased stability in test scores improves the test's ability to detect cognitive changes following injury, which increases the diagnostic utility of the test and allows for better return to play decision-making by reducing the risk of exposing an athlete to additional trauma while the brain may be at a heightened vulnerability to such trauma. Although the Speed Index increases the clinical utility of the test, the stability of the Memory index remains low. Irrespective of whether the two-factor or traditional four-composite approach is used, these data suggest that new baselines should occur on a yearly basis in order to maximize clinical utility. PMID- 26999706 TI - Herquline A, produced by Penicillium herquei FKI-7215, exhibits anti-influenza virus properties. AB - In the course of screening for new anti-influenza virus antibiotics, we isolated herquline A from a culture broth of the fungus, Penicillium herquei FKI-7215. Herquline A inhibited replication of influenza virus A/PR/8/34 strain in a dose dependent manner without exhibiting cytotoxicity against several human cell lines. It did not inhibit the viral neuraminidase. PMID- 26999707 TI - Sustainable Mechanism to Reduce Emergency Department (ED) Length of Stay: The Use of ED Holding (ED Transition) Orders to Reduce ED Length of Stay. AB - OBJECTIVE: The objective was to evaluate the effect of an emergency clinician initiated "ED admission holding order set" on emergency department (ED) treatment times and length of stay (LOS). We further describe the impact of a performance improvement strategy with sequential plan-do-study-act (PDSA) cycles used to influence the primary outcome measures, ED LOS, and disposition decision to patient gone (DDTPG) time, for admitted patients. METHODS: We developed and implemented an expedited, emergency physician-facilitated admission protocol that bypassed typical inpatient workflows requiring inpatient evaluations prior to the placement of admission orders. During the 48-month study period, ED flow metrics generated during the care of 27,580 admissions from the 24-month period prior to the intervention were compared to the 29,978 admissions that occurred during the 24-month period following the intervention. The intervention was the result of an in-depth, five-phase PDSA cycle quality improvement intervention evaluating ED flow, which identified the requirement of bedside inpatient evaluations prior admission order placement as being a "non-value-added" activity. ED output flow metrics evaluating the admission process were tracked for 24 months following the intervention and were compared to the 24 months prior. RESULTS: The use of an emergency physician-initiated admission holding order protocol resulted in sustainable reductions in ED LOS when comparing the 2 years prior to the intervention, with median LOS of 410 (interquartile range [IQR] = 295 to 543) and 395 (IQR = 283 to 527) minutes, to the 2 calendar years following the intervention, with the median LOS of 313 (IQR = 21 to 431) and 316 (IQR = 224 to 438) minutes, respectively. This overall reduction in ED LOS of nearly 90 minutes was found to be primarily the result of a decrease in the time from the emergency physician's admitting DDTPG times with median times of 219 (IQR = 150 to 306) and 200 (IQR = 136 to 286) minutes for the 2 years prior to the intervention compared to 89 (IQR = 58 to 138) and 92 (IQR = 60 to 147) minutes for the 2 years following the intervention. It is notable that there was a modest increase in the door to disposition decision of admission times during this same study period with annual medians of 176 (IQR = 112 to 261) and 178 (IQR = 129 to 316) minutes, respectively, for the 2 years prior to 207 (IQR = 129 to 316) and 202 (IQR = 127 to 305) minutes following the intervention. CONCLUSIONS: We conclude that the use of emergency physician-initiated holding orders can lead to marked reductions in ED LOS for admitted patients. Continued improvement can be demonstrated with an effective performance improvement initiative designed to continuously optimize the process change. PMID- 26999708 TI - Defect of zinc transporter ZRT1 ameliorates cadmium induced lipid accumulation in Saccharomyces cerevisiae. AB - Cadmium (Cd) is a non-essential divalent heavy metal that enters the cells by utilizing the transport pathways of the essential metals, like zinc (Zn), in Saccharomyces cerevisiae. This work focuses on Cd accumulation and its impact on deletion of Zn transporters Zrt1p and Zrt2p and lipid homeostasis. Cd exposure reduces the Zn levels in the mutant strains, and the effect was higher in zrt2Delta cells. Upon Cd exposure, the wild-type and zrt2Delta cells follow a similar pattern, but an opposite pattern was observed in zrt1Delta cells. The Cd influx and ROS levels were high in both wild-type cells and zrt2Delta cells but significantly reduced in zrt1Delta cells. Cd exposure led to accumulation of triacylglycerol and lipid droplets in wild-type cells and zrt2Delta cells but these levels were decreased in zrt1Delta cells. Hence, these studies suggest that the zrt1Delta cells provide resistance towards Cd and aid in the maintenance of lipid homeostasis in yeast cells. PMID- 26999709 TI - The Use of Narrative as a Treatment Approach for Obesity: A Storied Educational Program Description. AB - INTRODUCTION: Childhood obesity is a health care crisis according to the leading pediatric advocacy groups (National Medical Association, American Academy of Pediatrics, and American Diabetes Association) and the White House. The problem has reached epidemic proportions for all children, but it has an even greater impact on racial minorities. The subject of childhood obesity can lead to a host of medical, psychological, and social problems, including low self-esteem and discrimination.We wrote an interventional children's book and workbook (The Tale of Two Athletes: The Story of Jumper and The Thumper) and developed a three-step intervention based on the narrative. The intervention's purpose is to increase public awareness, reduce stigma, and to help members of underserved communities become more comfortable discussing obesity. METHODS: In classrooms and other community settings, a storied education program is presented to students of various ages. Interactive storytelling is the first step: live narration with direct listening and active participation. Didactic information on obesity is shared, including a sociocultural explanation for why the issue is more problematic among racial minorities. The audience is then introduced to the story of Jumper and The Thumper, two larger-than-life characters who experience different outcomes as a result of their choices about diet and exercise. True examples are described during the narration about these two young men, accompanied by cartoons and photographs for visual emphasis.The next step is reading: audience members are provided with a book to reinforce what was learned. Readers are allowed to more closely examine the importance of making healthy choices.Practicing positive behaviors and decision making through games and exercises from the companion workbook is the final step. These activities help children and their families live a healthier lifestyle. The goal is that these three steps, linked to a common narrative, will have a meaningful impact on obesity by creating behavioral change. RESULTS: Children, parents, and health care professionals have stated their enthusiastic response to the information and message and that they have made positive changes in children's eating and exercise habits. The program has been presented in community forums, churches, medical meetings, and elementary schools in at-risk communities. CONCLUSION: New strategies must be developed to lead, uplift, and empower through health and wellness education and through community collaboration if we are to change the direction of course toward this devastating condition that affects our most valuable commodity-our children. This community-based educational approach is a means to help recognize and treat obesity in underserved communities. PMID- 26999711 TI - Lifetime Perspectives on Primary Prevention of Atherosclerotic Cardiovascular Disease. PMID- 26999712 TI - An Efficient Strategy for Self-Assembly of DNA-Mimic Homochiral 1D Helical Cu(II) Chain from Achiral Flexible Ligand by Spontaneous Resolution. AB - Four helical copper complexes Cu[N(CN)2]2(Hhmp) (1), {Cu[N(CN)2]2(Hhmp)}infinity (2), (l-{Cu4[N(CN)2]2(hmp)4(CH3COO)2.CH3CN}infinity (3a), and d {Cu4[N(CN)2]2(hmp)4(CH3COO)2.CH3CN}infinity (3b) (Hhmp = 2 (hydroxymethyl)pyridine) have been prepared toward a mimic DNA structure. By changing the solvent and supplementary ligand, the structures can be successfully tuned from quasi-double-helical (complex 1) to racemic 1D single helix (complex 2), then the right (3a)-/left (3b)-handed double helices. The topologies of 3a and 3b may be considered as a mimic of DNA, where the Cu-O bonds between the two strands replace the hydrogen-bonding interactions in DNA. Solid-state circular dichroism spectra confirmed that 3a and 3b are optically active, respectively. Magnetic measurements for 1-3 indicated all complexes to be antiferromagnetic interactions. The best fitting results to the magnetic susceptibilities were J = 0.80 cm(-1), g = 2.11 for 1 and J1 = -9.22 cm(-1), J2 = 3.56 cm(-1), J3 = -9.49 cm(-1), g = 2.27 for 3. PMID- 26999710 TI - Post-transcriptional gene regulation in the biology and virulence of Candida albicans. AB - In the human fungal pathogen Candida albicans, remodelling of gene expression drives host adaptation and virulence. Recent studies revealed that in addition to transcription, post-transcriptional mRNA control plays important roles in virulence-related pathways. Hyphal morphogenesis, biofilm formation, stress responses, antifungal drug susceptibility and virulence in animal models require post-transcriptional regulators. This includes RNA binding proteins that control mRNA localization, decay and translation, as well as the cytoplasmic mRNA decay pathway. Comprehensive understanding of how modulation of gene expression networks drives C. albicans virulence will necessitate integration of our knowledge on transcriptional and post-transcriptional mRNA control. PMID- 26999713 TI - The muscular dystrophy coordinating committee action plan for the muscular dystrophies. PMID- 26999714 TI - Supercritical Fluid-Driven Polymer Phase Separation for Microlens with Tunable Dimension and Curvature. AB - Microlenses are highly sought as reliable means for high-resolution optical imaging at low illumination intensities. Plano-convex configuration with tunable dimension and curvature is an essential feature in the microlens fabrication. In this study, we present a facile and green route for preparing well-defined microlenses based on polymer phase separation in the presence of supercritical carbon dioxide (scCO2). The behaviors of linear polymethylmethacrylate protruded from cross-linked silicone network in scCO2 environment are investigated from the perspectives of thermodynamics and kinetics. Microlenses with dimensions from 2 to 15 MUm and contact angles from 55 degrees to 112 degrees are successfully obtained through the adjustment of the kinetic conditions and outgassing rate. With the tunable focal length, they exhibit intrinsic function of discerning submicroscale patterns that are unable to be observed directly under optical microscope. Moreover, size confinement on the substrate results in the generation of well-ordered microlens arrays, affording great promise for applications in bioimaging, photolithography, light harvesting, and optical nanosensing. PMID- 26999715 TI - Orange Peel Excision of Gland: A Novel Surgical Technique for Treatment of Gynecomastia. AB - INTRODUCTION: Gynecomastia is a common aesthetic problem faced by men with reported incidence as high as 65% with serious psychosocial impact. Although various techniques of liposculpture combined with glandular excision is the standard of treatment, many of the glandular excision techniques have inherent limitations and complications such as leaving a long scar, long operative time, contour abnormalities, and increased risk of hematoma. Here, we describe an innovative "the orange peel excision of gland (OPEG) technique" which overcomes these limitations with excellent cosmetic results. METHODS: A total of 38 breasts were operated in 20 patients (18 bilateral and 2 unilateral). All the patients underwent suction-assisted liposuction and glandular excision under general anesthesia by our OPEG technique. RESULTS: The average operative time per breast was 60 minutes. One patient had a small hematoma which did not require evacuation. The patient satisfaction rate was 95%. CONCLUSION: The technique has reduced operative time and avoids residual gland and hematoma with excellent aesthetic outcome. PMID- 26999716 TI - Silicone-Polytetrafluoroethylene Composite Implants for Asian Rhinoplasty. AB - BACKGROUND: Silicone and Gore-Tex implants are mainstays of Asian rhinoplasty. Silicone implants are inexpensive and wieldy, but may elicit a foreign-body reaction and are prone to migration. Gore-Tex implants are more biocompatible and capable of ingrowth but expensive. Silicone-polytetrafluoroethylene (PTFE) composites have a silicone core and PTFE liner. Composite implants have been marketed for several years, but are not yet established alternatives for rhinoplasty because of a lack of relevant reports. METHODS: From February 2012 to June 2015, 177 Asian patients underwent primary (n = 63) or secondary (n = 114) rhinoplasty using an I-shaped composite implant. One hundred fifty-nine women and 18 men were 19 to 72 years old (mean, 34 years) at the time of surgery. Composite implants were 1.5 to 5 mm thick and 3.8 to 4.5 cm long. Autologous cartilage from the septum, concha, or both was used for tip refinement in every case. Glabellar augmentation was performed in 19 (10.7%) cases. RESULTS: Follow-up was 6.0 months (range, 1-36 months). There were 19 (10.7%) complications including malposition/deviation (4.5%), erythema (2.3%), and infection (1.1%). Four patients were unsatisfied, citing inadequate dorsal height correction. There was an 8.8% revision rate; 7 of 12 revisions were for malposition/deviation. We did not observe implant step-offs or extrusion. There were no differences in outcomes after primary or secondary rhinoplasty, although there was a trend toward higher infection rate after primary rhinoplasty (P = 0.06). CONCLUSIONS: I-shaped silicone-PTFE composite implants are feasible for both primary and secondary augmentation rhinoplasty in Asians. Early outcomes data suggest an overall complication rate that is comparable to PTFE alone. PMID- 26999717 TI - Kaiso depletion attenuates transforming growth factor-beta signaling and metastatic activity of triple-negative breast cancer cells. AB - Triple-negative breast cancers (TNBCs) represent a subset of breast tumors that are highly aggressive and metastatic, and are responsible for a disproportionate number of breast cancer-related deaths. Several studies have postulated a role for the epithelial-to-mesenchymal transition (EMT) program in the increased aggressiveness and metastatic propensity of TNBCs. Although EMT is essential for early vertebrate development and wound healing, it is frequently co-opted by cancer cells during tumorigenesis. One prominent signaling pathway involved in EMT is the transforming growth factor-beta (TGFbeta) pathway. In this study, we report that the novel POZ-ZF transcription factor Kaiso is highly expressed in TNBCs and correlates with a shorter metastasis-free survival. Notably, Kaiso expression is induced by the TGFbeta pathway and silencing Kaiso expression in the highly invasive breast cancer cell lines, MDA-MB-231 (hereafter MDA-231) and Hs578T, attenuated the expression of several EMT-associated proteins (Vimentin, Slug and ZEB1), abrogated TGFbeta signaling and TGFbeta-dependent EMT. Moreover, Kaiso depletion attenuated the metastasis of TNBC cells (MDA-231 and Hs578T) in a mouse model. Although high Kaiso and high TGFbetaR1 expression is associated with poor overall survival in breast cancer patients, overexpression of a kinase active TGFbetaR1 in the Kaiso-depleted cells was insufficient to restore the metastatic potential of these cells, suggesting that Kaiso is a key downstream component of TGFbeta-mediated pro-metastatic responses. Collectively, these findings suggest a critical role for Kaiso in TGFbeta signaling and the metastasis of TNBCs. PMID- 26999718 TI - A monoclonal antibody targeting ErbB2 domain III inhibits ErbB2 signaling and suppresses the growth of ErbB2-overexpressing breast tumors. AB - The anti-ErbB2 antibodies trastuzumab and pertuzumab in combination have recently been approved for the treatment of patients with ErbB2-positive metastatic breast cancer. Pertuzumab, which binds to ErbB2 near the center of domain II, and trastuzumab, which binds to the juxtamembrane region of ErbB2 domain IV, directly interfere with domain II- and domain IV-mediated heterodimerization contacts, respectively. In this study, we report a novel anti-ErbB2 antibody, 3E10, which binds to an epitope in domain III that appears to be located opposite to the dimerization interfaces in domain II and domain IV of ErbB2. Our data show that the 3E10 antibody inhibits ErbB2 heterodimerization via a mechanism that strikingly differs from trastuzumab and pertuzumab. It could be speculated that the 3E10 antibody may affect ErbB2 heterodimerization by causing major conformational changes of ErbB2. Furthermore, 3E10 provides synergistic inhibition of ErbB2 heterodimerization and signaling in combination with either trastuzumab or pertuzumab. The combination of these three anti-ErbB2 antibodies that have complementary mechanisms of action appears to be an extremely potent ErbB2 heterodimerization blocker. Compared with trastuzumab plus pertuzumab, the combination of trastuzumab, pertuzumab and 3E10 provides a more potent blockade of ErbB2 signaling. Consistent with this, trastuzumab plus pertuzumab plus 3E10 results in greater in vitro and in vivo antitumor activity in ErbB2 overexpressing breast tumor models, suggesting its potential use for treating ErbB2-overexpressing breast cancer. PMID- 26999719 TI - Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. AB - The retinal pigment epithelium (RPE), a monolayer located between the photoreceptors and the choroid, is constantly damaged by oxidative stress, particularly because of reactive oxygen species (ROS). As the RPE, because of its physiological functions, is essential for the survival of the retina, any sustained damage may consequently lead to loss of vision. Exosomes are small membranous vesicles released into the extracellular medium by numerous cell types, including RPE cells. Their cargo includes genetic material and proteins, making these vesicles essential for cell-to-cell communication. Exosomes may fuse with neighbouring cells influencing their fate. It has been observed that RPE cells release higher amounts of exosomes when they are under oxidative stress. Exosomes derived from cultured RPE cells were isolated by ultracentrifugation and quantified by flow cytometry. VEGF receptors (VEGFR) were analysed by both flow cytometry and Western blot. RT-PCR and qPCR were conducted to assess mRNA content of VEGFRs in exosomes. Neovascularization assays were performed after applying RPE exosomes into endothelial cell cultures. Our results showed that stressed RPE cells released a higher amount of exosomes than controls, with a higher expression of VEGFR in the membrane, and enclosed an extra cargo of VEGFR mRNA. Angiogenesis assays confirmed that endothelial cells increased their tube formation capacity when exposed to stressed RPE exosomes. PMID- 26999720 TI - Increased iron levels and lipid peroxidation in a Mediterranean population of Spain. AB - BACKGROUND: Many chronic diseases are adversely affected by elevated iron levels. It has been speculated that this relationship is mediated by increased oxidative stress, due to the ability of iron to generate reactive oxygen species. The aim of this study was to assess the relationship between elevated iron levels and lipid peroxidation in Caucasian adults residing in the north-eastern Mediterranean region of Spain. MATERIALS AND METHODS: This cross-sectional case control study included 300 subjects: 150 adults displaying elevated iron levels (cases) selected from a representative sample of our general population and 150 age- and sex-matched adults exhibiting normal iron levels (controls). Dietary assessment (3-day food records), iron biomarkers (serum iron, ferritin and transferrin saturation) and lipid profile were determined. Elevated iron levels were defined by high serum ferritin (SF>110 MUg/L in women and>200 MUg/L in men) and/or transferrin saturation (TS)>45%. Oxidized low-density lipoprotein (oxLDL) plasma levels were measured, and oxLDL/LDL-cholesterol ratio was calculated to estimate lipid peroxidation. Multiple linear regression (MLR) models were applied. RESULTS: Individuals with elevated serum iron levels showed increased oxLDL/LDL ratio, but not oxLDL levels, compared to control subjects (20.92 +/- 4.89 U/mmol vs. 19.72 +/- 3.573 U/mmol, P = 0.028). These results were further confirmed by the regression models adjusted for demographic characteristics, diet, lipid profile and inflammation. Importantly, higher serum levels of triglycerides, LDL-cholesterol and lower intake of Vitamin E increased lipid peroxidation. CONCLUSIONS: In our general population, we have observed that higher circulating levels of iron, measured by serum ferritin and/or TS, increased lipid peroxidation (measured by oxLDL/LDL ratio). PMID- 26999721 TI - Why the Timing? PMID- 26999722 TI - Transit Use by Children and Adolescents: An Overlooked Source of and Opportunity for Physical Activity? AB - BACKGROUND: The potential for adults to accrue significant physical activity through public transit use is a topic of interest. However, there are no data on analogous questions among children. The goal of this analysis was to quantify patterns of transit use and correlates of transit-related physical activity among children aged 5 to 17 years. METHODS: Data for this cross-sectional study came from the 2012 California Household Travel Survey. Probit regressions modeled the probability of transit use; negative binomial regressions modeled minutes/day in transit-related active travel. RESULTS: Public transit use accounted for 3% of trips in California in 2012. Older Hispanic youth and those residing in areas with greater housing density and county size had a higher probability of transit use. Driver licensure, home ownership, household income, and vehicles in household were negatively correlated with public transit use. Race/ethnicity, income, and transit type were correlated with time spent in active travel to/ from transit. CONCLUSIONS: Given its importance as a source of physical activity for some children, researchers should consider assessment of public transit related activity in physical activity measurement instruments. Efforts to encourage active travel should consider how to incorporate transit-related activity, both from a measurement perspective and as an intervention strategy. PMID- 26999723 TI - A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers. AB - Stress exposure during early development is known to produce long-term mental health deficits. Stress promotes poor lifestyle choices such as poor diet. Early life adversity and diets high in fat and sugar (HFHS) are known to affect anxiety and memory. However additive effects of HFHS and stress during early development are less explored. Here, we examined whether early life stress (ELS) simulated by limited nesting (LN) induces anxiety-like behaviour and cognitive deficits that are modulated by HFHS diet. We examined key hippocampal markers involved in anxiety and cognition, testing the hypothesis that post-weaning HFHS following ELS would ameliorate anxiety-like behaviour but worsen memory and associated hippocampal changes. Sprague-Dawley rats were exposed to LN, postnatal days 2-9, and at weaning, male siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, LN-HFHS, n=11-15/group). Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM) at 10 weeks and spatial and object recognition tested at 11 weeks of age. Rats were culled at 13 weeks. Hippocampal mRNA expression was measured using TaqMan((r)) Array Micro Fluidic cards (Life Technologies). As expected HFHS diet increased body weight; LN and control rats had similar weights at 13 weeks, energy intake was also similar across groups. LN-Chow rats showed increased anxiety-like behaviour relative to control rats, but this was reversed by HFHS diet. Spatial and object recognition memory were unaltered by LN exposure or consumption of HFHS diet. Hippocampal glucocorticoid receptor (GR) protein was not affected by LN exposure in chow rats, but was increased by 45% in HFHS rats relative to controls. Hippocampal genes involved in plasticity and mood regulation, GSKalpha and GSKbeta were affected, with reductions in GSKbeta under both diet conditions, and reduced GSKalpha only in LN-HFHS versus Con-HFHS. Interestingly, HFHS diet and LN exposure independently reduced expression of Akt3 mRNA, a key gene involved post natal brain development. In summary, while an energy rich diet ameliorated anxiety-like behaviour induced by LN exposure, it significantly altered key genes that are essential for hippocampal development. PMID- 26999724 TI - Screening and treatment of latent tuberculosis infection among HIV-infected patients in resource-rich settings. AB - Current international guidelines recommend screening and treatment of latent tuberculosis (TB) infection in HIV-infected patients in all settings. The main factors affecting the risk of TB in HIV-infected patients include the level of immunosuppression, coverage of antiretroviral therapy and local TB burden. In resource-rich settings where antiretroviral therapy is more accessible and HIV infected patients are expected to be diagnosed at an earlier stage, local TB burden remains a key factor on their risk of TB. This article reviewed the epidemiology of latent TB infection among the adult HIV-infected patients, and the use and benefit of screening and treatment of latent TB infection in resource rich settings in the past decade. While such practice should be continued in countries with medium or high TB burden, targeted screening and treatment only for HIV-infected patients with additional risk factors for TB might be a more practical option in resource-rich countries with low TB burden. PMID- 26999725 TI - Natural radioactivity measurements in Pahang State, Malaysia. AB - This study was aimed at providing the baseline data of terrestrial gamma dose rates and natural radioactivity to assess the corresponding health risk in the ambient environment of the Pahang State. Terrestrial gamma radiation (TGR) from 640 locations was measured with the mean value found to be 176 +/- 5 nGy h(-1). Ninety-eight soil samples were analysed using a high-purity germanium detector (HPGe), and the mean concentrations of the radionuclides (226)Ra, (232)Th and (40)K are 110 +/- 3, 151 +/- 5 and 542 +/- 51 Bq kg(-1), respectively.(226)Ra and (232)Th concentrations were found to be three times the world average, while that of (40)K is quite higher than the world average value. The acid-intrusive geological formation has the highest mean concentrations for (226)Ra (215 +/- 6 Bq kg(-1)), (232)Th (384 +/- 12 Bq kg(-1)) and (40)K (1564 +/- 153 Bq kg(-1)). The radium equivalent activities (Req) and the external hazard index (Hex) for the various soil types were also calculated. Some of the soil types were found to have values exceeding the internationally recommended levels of 370 Bq kg(-1) and the unity value, respectively. PMID- 26999726 TI - Do the early development of gestures and receptive and expressive language predict language skills at 5;0 in prematurely born very-low-birth-weight children? AB - It is unclear what the predictive value of very early development of gestures and language is on later language ability in prematurely born very-low-birth-weight (VLBW; birth weight <=1500g) children. The aim of the present study was to analyse the predictive value of early gestures and a receptive lexicon measured between the ages of 0;9 and 1;3, as well as the predictive value of receptive and expressive language ability at 2;0 for language skills at 5;0 in VLBW children. The subjects were 29 VLBW children and 28 full-term children whose language development has been followed intensively between the ages of 0;9 and 2;0 using the Finnish version of the MacArthur Developmental Inventory and the Reynell Developmental Language Scales (RDLS III). At 5;0, five selected verbal subtests of the Nepsy II test and the Boston Naming Test (BNT) were used to assess children's language skills. For the first time in VLBW children, the development of gestures measured between the ages of 0;9 and 1;3 was shown to correlate significantly and positively with language skills at 5;0. In addition, both receptive and expressive language ability measured at 2;0 correlated significantly and positively with later language skills in both groups. Moreover, according to the hierarchical regression analysis, the receptive language score of the RDLS III at 2;0 was a clear and significant predictor for language skills at 5;0 in both groups. The findings particularly underline the role of early receptive language as a significant predictor for later language ability in VLBW children. The results provide evidence for a continuity between early language development and later language skills. LEARNING OUTCOMES: After reading this article, readers will understand the associations between the very early (<=2 years of age) development of gestures and language (i.e. early receptive lexicon, expressive lexicon at 2;0, receptive and expressive language ability at 2;0) and the language skills at 5;0 in prematurely born very-low-birth-weight (VLBW) children. In addition, readers will understand the heterogeneity of the group of VLBW children. The information presented in this article is informative for those who work in a clinical context and who want to be able to identify those VLBW children who need support for their language development at an early age. PMID- 26999728 TI - When the Gold Standard Loses Its Luster, Perhaps It Is Time to Change Nomenclature. PMID- 26999727 TI - Transcatheter aortic valve implantation today and tomorrow. AB - Aortic stenosis is the most common valvular heart disease in Western industrial countries (including Switzerland) with a prevalence of about 5% in the population aged 75 and over. If left untreated, symptomatic patients have a rate of death of more than 50% within 2 years. As a result of age and elevated surgical risk, an important proportion of elderly patients are not referred to surgery. Thus, the introduction of transcatheter aortic valve implantation (TAVI) in 2002 has initiated a paradigm shift in the treatment of patients with symptomatic, severe aortic stenosis. The early technical and procedural success of this minimal invasive treatment in high-risk patients has promoted further innovation and development of transcatheter heart valve (THV) systems during the last 13 years. Downsizing of the delivery catheters along with technical improvements aiming to reduce postprocedural paravalvular regurgitation have resulted in a significant reduction in mortality. As a consequence, TAVI is nowadays established as safe and effective treatment for selected inoperable and high-risk patients. Ongoing studies are investigating the outcome of intermediate risk patients allocated to either surgical aortic valve replacement (SAVR) or TAVI. Despite these advancements, some specific areas of concern still require attention and need further investigations including conduction disturbances, valve degeneration and antithrombotic management. Although the off-label use of TAVI devices in the mitral, tricuspid or pulmonary position has recently developed, important limitations still apply and careful patient selection remains crucial. This review aims to summarise the available clinical evidence of transcatheter aortic valve treatment during the last 13 years and to provide a glimpse of future technologies. PMID- 26999729 TI - MRI of Polyethylene Tibial Inserts in Total Knee Arthroplasty: Normal and Abnormal Appearances. AB - OBJECTIVE: The purpose of this study was to describe the normal and abnormal MRI appearances of polyethylene tibial inserts. Subjects who underwent MRI before revision total knee arthroplasty were identified. The polyethylene tibial insert's shape was categorized on MRI, and the presence of abnormalities was noted. CONCLUSION: The shape of the polyethylene tibial insert varied with the design. Polyethylene tibial insert abnormalities seen on MRI included displacement and fracture. MRI distinguishes various designs of polyethylene tibial inserts and can show associated abnormalities. PMID- 26999730 TI - Effect of Behavior Modification on Outcome in Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial. AB - OBJECTIVES: Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. DESIGN: Stratified open cluster randomized trial. SETTING: A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. PARTICIPANTS: A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. INTERVENTION: All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. MAIN OUTCOME MEASURE: The primary outcome measures were 1) the non adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. RESULTS: The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6+/-5.8 ml/min/1.73 m2/year, group B: 2.4+/-5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4+/-5.9 ml/min/1.73 m2/year, group B: 1.9+/-4.4 ml/min/1.73 m2/year, p = 0.03). CONCLUSION: Our care system achieved behavior modification of CKD patients, namely, significantly lower discontinuous clinical visits, and behavior modification of both GPs and nephrologists, namely significantly higher referral and co-treatment rates, resulting in the retardation of CKD progression, especially in patients with proteinuric Stage 3 CKD. TRIAL REGISTRATION: The University Hospital Medical Information Network clinical trials registry UMIN000001159. PMID- 26999731 TI - Rapid evolution and gene expression: a rapidly evolving Mendelian trait that silences field crickets has widespread effects on mRNA and protein expression. AB - A major advance in modern evolutionary biology is the ability to start linking phenotypic evolution in the wild with genomic changes that underlie that evolution. We capitalized on a rapidly evolving Hawaiian population of crickets (Teleogryllus oceanicus) to test hypotheses about the genomic consequences of a recent Mendelian mutation of large effect which disrupts the development of sound producing structures on male forewings. The resulting silent phenotype, flatwing, persists because of natural selection imposed by an acoustically orienting parasitoid, but it interferes with mate attraction. We examined gene expression differences in developing wing buds of wild-type and flatwing male crickets using RNA-seq and quantitative proteomics. Most differentially expressed (DE) transcripts were down-regulated in flatwing males (625 up vs. 1716 down), whereas up- and down-regulated proteins were equally represented (30 up and 34 down). Differences between morphs were clearly not restricted to a single pathway, and we recovered annotations associated with a broad array of functions that would not be predicted a priori. Using a candidate gene detection test based on homology, we identified 30% of putative Drosophila wing development genes in the cricket transcriptome, but only 10% were DE. In addition to wing-related annotations, endocrine pathways and several biological processes such as reproduction, immunity and locomotion were DE in the mutant crickets at both biological levels. Our results illuminate the breadth of genetic pathways that are potentially affected in the early stages of adaptation. PMID- 26999732 TI - The allure of mass spectrometry: From an earlyday chemist's perspective. AB - This reminiscing review article is an account of the author's fascination and involvements with mass spectrometry from the perspective of an organic chemist with an interest in natural product chemistry. It covers a period from 1961 through the mid 1990s as mass spectrometry evolved form a novelty technique to become a most widely used analytical technique. Following a brief synopsis of my pathway to mass spectrometry, my research efforts in this field are presented with a focus mainly on evolving principles and technologies which I had personal involvements with. To provide historical perspectives, discussions of these developments are accompanied by brief outlines of the relevant state-of-the-art, shedding light on the technical and conceptual challenges encountered during those early days in mass spectrometry. Examples are presented of my involvements with basic and applied research in mass spectrometry during graduate studies at Stanford University and close to three decade tenure in pharmaceutical research at Syntex Research. My basic research interests focused mainly on principles of electron ionization induced fragmentation mechanisms, with an emphasis on steroids and other model compounds. Extensive deuterium labeling evidence was used to determine the fragmentation mechanisms of the diagnostically significant ions in the spectra of numerous model compounds, uncovering examples of wide ranging hydrogen transfers, skeletal rearrangements, methyl and phenyl migrations, stereoselective fragmentations and low and high energy fragmentation processes. Depiction of the industrial research phase of my career includes comments on the pivotal role mass spectrometry played on advancing modern pharmaceutical research. Examples are presented of involvements with instrumental developments and a few select cases of applied research, including studies of bile mechanisms in vertebrates, identification of bisphenol-A leaching from sterilized polycarbonate containers, high sensitivity TCDD analyses and other projects. Reflecting on my services for the mass spectrometry society, involvements with the co-founding and 12 year chairing of the Asilomar Conference on Mass Spectrometry and founding of the Bay Area Mass Spectrometry regional MS discussion group, as part of my services for the mass spectrometry community, are presented in some detail. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:520 542, 2017. PMID- 26999734 TI - A microfluidic array for real-time live-cell imaging of human and rodent pancreatic islets. AB - In this study, we present a microfluidic array for high-resolution imaging of individual pancreatic islets. The device is based on hydrodynamic trapping principle and enables real-time analysis of islet cellular responses to insulin secretagogues. This device has significant advantages over our previously published perifusion chamber device including significantly increased analytical power and assay sensitivity, as well as improved spatiotemporal resolution. The islet array, with live-cell multiparametric imaging integration, provides a better tool to understand the physiological and pathophysiological changes of pancreatic islets through the analysis of single islet responses. This platform demonstrates the feasibility of array-based islet cellular analysis and opens up a new modality to conduct informative and quantitive evaluation of islets and cell-based screening for new diabetes treatments. PMID- 26999733 TI - 3D Motions of Iron in Six-Coordinate {FeNO}(7) Hemes by Nuclear Resonance Vibration Spectroscopy. AB - The vibrational spectrum of a six-coordinate nitrosyl iron porphyrinate, monoclinic [Fe(TpFPP)(1-MeIm)(NO)] (TpFPP=tetra-para-fluorophenylporphyrin; 1 MeIm=1-methylimidazole), has been studied by oriented single-crystal nuclear resonance vibrational spectroscopy (NRVS). The crystal was oriented to give spectra perpendicular to the porphyrin plane and two in-plane spectra perpendicular or parallel to the projection of the FeNO plane. These enable assignment of the FeNO bending and stretching modes. The measurements reveal that the two in-plane spectra have substantial differences that result from the strongly bonded axial NO ligand. The direction of the in-plane iron motion is found to be largely parallel and perpendicular to the projection of the bent FeNO on the porphyrin plane. The out-of-plane Fe-N-O stretching and bending modes are strongly mixed with each other, as well as with porphyrin ligand modes. The stretch is mixed with v50 as was also observed for dioxygen complexes. The frequency of the assigned stretching mode of eight Fe-X-O (X=N, C, and O) complexes is correlated with the Fe-XO bond lengths. The nature of highest frequency band at ~560 cm(-1) has also been examined in two additional new derivatives. Previously assigned as the Fe-NO stretch (by resonance Raman), it is better described as the bend, as the motion of the central nitrogen atom of the FeNO group is very large. There is significant mixing of this mode. The results emphasize the importance of mode mixing; the extent of mixing must be related to the peripheral phenyl substituents. PMID- 26999737 TI - Tissue-specific designs of stem cell hierarchies. AB - Recent work in the field of stem cell biology suggests that there is no single design for an adult tissue stem cell hierarchy, and that different tissues employ distinct strategies to meet their self-renewal and repair requirements. Stem cells may be multipotent or unipotent, and can exist in quiescent or actively dividing states. 'Professional' stem cells may also co-exist with facultative stem cells, which are more specialized daughter cells that revert to a stem cell state under specific tissue damage conditions. Here, we discuss stem cell strategies as seen in three solid mammalian tissues: the intestine, mammary gland and skeletal muscle. PMID- 26999735 TI - LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. AB - Long non-coding RNAs (lncRNAs) have emerged as critical regulators in various cellular processes. However, the potential involvement of lncRNAs in kinase signalling remains largely unknown. AMP-activated protein kinase (AMPK) acts as a critical sensor of cellular energy status. Here we show that the lncRNA NBR2 (neighbour of BRCA1 gene 2) is induced by the LKB1-AMPK pathway under energy stress. On energy stress, NBR2 in turn interacts with AMPK and promotes AMPK kinase activity, thus forming a feed-forward loop to potentiate AMPK activation during energy stress. Depletion of NBR2 attenuates energy-stress-induced AMPK activation, resulting in unchecked cell cycling, altered apoptosis/autophagy response, and increased tumour development in vivo. NBR2 is downregulated and its low expression correlates with poor clinical outcomes in some human cancers. Together, the results of our study uncover a mechanism coupling lncRNAs with metabolic stress response, and provides a broad framework to understand further the regulation of kinase signalling by lncRNAs. PMID- 26999739 TI - Correction: Quantitative Determination of Technological Improvement from Patent Data. PMID- 26999736 TI - SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture. AB - Centrioles are critical for the formation of centrosomes, cilia and flagella in eukaryotes. They are thought to assemble around a nine-fold symmetric cartwheel structure established by SAS-6 proteins. Here, we have engineered Chlamydomonas reinhardtii SAS-6-based oligomers with symmetries ranging from five- to ten-fold. Expression of a SAS-6 mutant that forms six-fold symmetric cartwheel structures in vitro resulted in cartwheels and centrioles with eight- or nine-fold symmetries in vivo. In combination with Bld10 mutants that weaken cartwheel microtubule interactions, this SAS-6 mutant produced six- to eight-fold symmetric cartwheels. Concurrently, the microtubule wall maintained eight- and nine-fold symmetries. Expressing SAS-6 with analogous mutations in human cells resulted in nine-fold symmetric centrioles that exhibited impaired length and organization. Together, our data suggest that the self-assembly properties of SAS-6 instruct cartwheel symmetry, and lead us to propose a model in which the cartwheel and the microtubule wall assemble in an interdependent manner to establish the native architecture of centrioles. PMID- 26999738 TI - Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells. AB - Aberrant Notch signalling has been linked to many cancers including choroid plexus (CP) tumours, a group of rare and predominantly paediatric brain neoplasms. We developed animal models of CP tumours, by inducing sustained expression of Notch1, that recapitulate properties of human CP tumours with aberrant NOTCH signalling. Whole-transcriptome and functional analyses showed that tumour cell proliferation is associated with Sonic Hedgehog (Shh) in the tumour microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumour cells possess a solitary primary cilium as a result of Notch mediated suppression of multiciliate differentiation. A Shh-driven signalling cascade in the primary cilium occurs in tumour cells but not in epithelial cells. Lineage studies show that CP tumours arise from monociliated progenitors in the roof plate characterized by elevated Notch signalling. Abnormal SHH signalling and distinct ciliogenesis are detected in human CP tumours, suggesting the SHH pathway and cilia differentiation as potential therapeutic avenues. PMID- 26999740 TI - miRNA-503 Promotes Tumor Progression and Is Associated with Early Recurrence and Poor Prognosis in Human Colorectal Cancer. AB - OBJECTIVES: MicroRNA (miR)-503 is downregulated in several cancers and plays a tumor-suppressive role in carcinogenesis. However, the miR-503 expression pattern, its clinical significance and its molecular mechanism in colorectal cancer (CRC) have not been investigated. METHODS: We analyzed miR-503 expression in normal mucosa (n = 20), adenoma (n = 27) and CRC (n = 20). We quantified miR 503 expression in an independent cohort (n = 191) and investigated the clinical significance of miR-503 in CRC. CRC cell lines were transfected with anti-miR-503 to assess its function and target gene. RESULTS: miR-503 expression increased according to the adenoma-carcinoma sequence. High miR-503 expression was significantly associated with large tumor size, serosal invasion, lymphatic and venous invasion as well as lymph node metastasis. CRC patients with high miR-503 expression had significantly earlier relapse and poorer prognosis than those with low expression. miR-503 was an independent recurrence marker in stage I/II CRC. In vitro, attenuated miR-503 expression resulted in inhibition of proliferation, invasion and migration and acquisition of anoikis of CRC cells. The putative target gene (calcium-sensing receptor) was significantly upregulated after miR 503 attenuation. CONCLUSIONS: miR-503 acts as an 'onco-miR' in CRC. High miR-503 expression is associated with early recurrence and poor prognosis in CRC. PMID- 26999741 TI - Fast Coding Unit Encoding Mechanism for Low Complexity Video Coding. AB - In high efficiency video coding (HEVC), coding tree contributes to excellent compression performance. However, coding tree brings extremely high computational complexity. Innovative works for improving coding tree to further reduce encoding time are stated in this paper. A novel low complexity coding tree mechanism is proposed for HEVC fast coding unit (CU) encoding. Firstly, this paper makes an in depth study of the relationship among CU distribution, quantization parameter (QP) and content change (CC). Secondly, a CU coding tree probability model is proposed for modeling and predicting CU distribution. Eventually, a CU coding tree probability update is proposed, aiming to address probabilistic model distortion problems caused by CC. Experimental results show that the proposed low complexity CU coding tree mechanism significantly reduces encoding time by 27% for lossy coding and 42% for visually lossless coding and lossless coding. The proposed low complexity CU coding tree mechanism devotes to improving coding performance under various application conditions. PMID- 26999743 TI - Utility of an Algorithm to Increase the Accuracy of Medication History in an Obstetrical Setting. AB - BACKGROUND: In an obstetrical setting, inaccurate medication histories at hospital admission may result in failure to identify potentially harmful treatments for patients and/or their fetus(es). METHODS: This prospective study was conducted to assess average concordance rates between (1) a medication list obtained with a one-page structured medication history algorithm developed for the obstetrical setting and (2) the medication list reported in medical records and obtained by open-ended questions based on standard procedures. Both lists were converted into concordance rate using a best possible medication history approach as the reference (information obtained by patients, prescribers and community pharmacists' interviews). RESULTS: The algorithm-based method obtained a higher average concordance rate than the standard method, with respectively 90.2% [CI95% 85.8-94.3] versus 24.6% [CI95%15.3-34.4] concordance rates (p<0.01). CONCLUSION: Our algorithm-based method strongly enhanced the accuracy of the medication history in our obstetric population, without using substantial resources. Its implementation is an effective first step to the medication reconciliation process, which has been recognized as a very important component of patients' drug safety. PMID- 26999742 TI - Oestrogens Downregulate Tissue Factor Pathway Inhibitor through Oestrogen Response Elements in the 5'-Flanking Region. AB - Oestrogens influence the pathology and development of hormone-sensitive breast cancers. Tissue factor pathway inhibitor (TFPI) has been shown to be associated with breast cancer pathogenesis. Recently, we found TFPI mRNA levels to be significantly reduced by oestrogens in a breast cancer cell line (MCF7), a process mediated through the oestrogen receptor alpha (ERalpha). The aim of the present study was to investigate the mechanism(s) by which oestrogens may regulate TFPI at the transcriptional level. The TFPI 5'-flanking region contains three oestrogen response element (ERE) half-sites at positions -845, -769 and 50. Constructs containing the wild type or mutated ERE half-sites of the TFPI 5' flanking region were generated in a luciferase reporter gene vector and transiently co-transfected with an ERalpha expression vector into HEK293 cells and subsequently treated with oestrogens. We found that luciferase activity was significantly downregulated after oestrogen stimulation in cells transfected with the wild type construct, an effect that was abolished by mutating either ERE half sites. Electrophoretic mobility shift assay suggested direct and specific interaction of ERalpha with the ERE half-sites in the TFPI 5'-flanking region. Chromatin immunoprecipitation showed that ERalpha was recruited to the region 899 to -578 of the TFPI 5'-flanking region in vivo, where the ERE half-sites -845 and -769 are located. Our results indicate that ERalpha can interact with all three ERE half-sites in the TFPI 5'-flanking region and thus participate in the repression of oestrogen mediated TFPI transcription in breast cancer cells. PMID- 26999745 TI - In vitro inhibitory activity of probiotic products against oral Candida species. AB - AIMS: To evaluate the inhibitory activity of probiotics against oral Candida species. METHODS AND RESULTS: Four commercial probiotic products were screened. Bacillus subtilis R0179 was found to have a significant antifungal effect. Bacillus subtilis-Candida interactions were evaluated using disc diffusion tests, confocal laser scanning microscopy, scanning electron microscopy and interaction with engineered human oral mucosa tissue. Bacillus subtilis exhibited clear zones of inhibition for Candida albicans and Candida parapsilosis but not for Candida krusei. A remarkable reduction in the number of Candida cells and abundant Candida cell death were visualized with confocal laser scanning microscopy. Shrinkage and deformation of Candida cells was observed using scanning electron microscopy. Culture of C. albicans on engineered human oral mucosa tissues resulted in the presence of a large number of yeast cells on the tissue surface and the development of large-scale tissue damage. However, comparatively fewer Candida cells were observed on B. subtilis-treated tissues. We also use ultra performance liquid chromatography/time of flight mass spectrometry (UPLC/TOF MS) to explore the preliminary antifungal mechanism of B. subtilis R0179 and to detect that whether it can secrete an antifungal agent, Iturin A. CONCLUSIONS: Bacillus subtilis R0179 exhibits a significant inhibitory effect on the growth of Candida species. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus subtilis has the potential to be used in the prevention or treatment of oral candidiasis. PMID- 26999744 TI - Preterm Birth and Low Birth Weight after In Utero Exposure to Antiretrovirals Initiated during Pregnancy in Yaounde, Cameroon. AB - BACKGROUND: Effects of antiretroviral therapy (ART) on birth outcomes remain controversial. OBJECTIVE: To assess the impact of antenatal exposure to ART on the occurrence of preterm birth (PTB) and low birth weight (LBW). METHODS: A cross-sectional study conducted at the Essos Hospital Center in Yaounde from 2008 to 2011 among HIV vertically exposed infants with two distinct maternal antiretroviral experiences: monotherapy group (Zidovudine, ZDV) and the combination ART group (cART). Mothers already receiving cART before pregnancy were ineligible. In both groups, events of PTB (<37 weeks) and LBW (<2,500g) were analyzed using univariate and multivariate logistic regression; with p<0.05 considered statistically significant. RESULTS: Of the 760 infants, 481 were born from cART-exposed mothers against 279 from maternal-ZDV. Median maternal CD4 count was 378 [interquartile range (IQR): 253-535] cells/mm3. Median duration of ART at onset of delivery was 13 [IQR: 10-17] weeks. In the cART-group, 64.9% (312/481) of mothers were exposed to Zidovudine/Lamuvidine/Nevirapine and only 2% (9/481) were on protease inhibitor-based regimens. Events of PTB were not significantly higher in the cART-group compared to the ZDV-group (10.2% vs. 6.4% respectively, p = 0.08), while onsets of LBW were significantly found in the cART group compared to ZDV-group (11.6% vs. 7.2% respectively, p = 0.05). Other factors (parity, maternal age at delivery or CD4 cell count) were not associated with PTB. CONCLUSION: cART, initiated during pregnancy, would be an independent factor of LBW. In the era of option B+ (lifelong ART to all HIV-pregnant women), further studies would guide towards measures limiting onsets of LBW. PMID- 26999746 TI - A Central Line Care Maintenance Bundle for the Prevention of Central Line Associated Bloodstream Infection in Non-Intensive Care Unit Settings. AB - OBJECTIVE To evaluate a central line care maintenance bundle to reduce central line-associated bloodstream infection (CLABSI) in non-intensive care unit settings. DESIGN Before-after trial with 12-month follow-up period. SETTING A 1,250-bed teaching hospital. PARTICIPANTS Patients with central lines on 8 general medicine wards. Four wards received the intervention and 4 served as controls. INTERVENTION A multifaceted catheter care maintenance bundle consisting of educational programs for nurses, update of hospital policies, visual aids, a competency assessment, process monitoring, regular progress reports, and consolidation of supplies necessary for catheter maintenance. RESULTS Data were collected for 25,542 catheter-days including 43 CLABSI (rate, 1.68 per 1,000 catheter-days) and 4,012 catheter dressing observations. Following the intervention, a 2.5% monthly decrease in the CLABSI incidence density was observed on intervention floors but this was not statistically significant (95% CI, -5.3% to 0.4%). On control floors, there was a smaller but marginally significant decrease in CLABSI incidence during the study (change in monthly rate, -1.1%; 95% CI, -2.1% to -0.1%). Implementation of the bundle was associated with improvement in catheter dressing compliance on intervention wards (78.8% compliance before intervention vs 87.9% during intervention/follow-up; P<.001) but improvement was also observed on control wards (84.9% compliance before intervention vs 90.9% during intervention/follow-up; P=.001). CONCLUSIONS A multifaceted program to improve catheter care was associated with improvement in catheter dressing care but no change in CLABSI rates. Additional study is needed to determine strategies to prevent CLABSI in non-intensive care unit patients. Infect Control Hosp Epidemiol 2016;37:692-698. PMID- 26999747 TI - Prevalence and cumulative incidence of food hyper-sensitivity in the first 10 years of life. AB - BACKGROUND: Prevalence, incidence and natural history of food hypersensitivity (FHS) and its trends in an unselected cohort of older children are unclear. METHODS: A birth cohort born on the Isle of Wight (UK) between 2001 and 2002 was followed up prospectively. Children were clinically examined and skin prick tested at set times and invited for food challenges when indicated. At 10 years of age, children were also invited for a blood test. RESULTS: A total of 969 children were recruited at 12 weeks of pregnancy, and 92.9%, 88.5%, 91.6% and 85.3% were assessed at 1, 2, 3 and 10 years. Prevalence of sensitization to any allergen over 10 years was 186 of 969 (19.2%; 95% CI: 16.84-21.8) and 108 of 969 (11.2%; 95% CI: 9.31-13.29) children were sensitized to at least one predefined food allergen. Excluding wheat (due to cross-reactivity with pollen), 40 of 969 (4.1%; 95% CI: 3.19-5.32) children were sensitized to a predefined food allergen. Using food challenges and/or a good clinical history, the cumulative incidence of food hypersensitivity (FHS) in the first decade of life was 64 of 947 (6.8%, 95% CI: 5.2-8.4), while the prevalence of FHS at 10 years was 30 of 827 (3.6%, 95% CI: 2.54-5.15). The vast majority, 25 of 827 (3.0%, 95% CI: 1.8-4.2), suffered from IgE-mediated food allergy, while 5 of 827 (0.6%, 95% CI: 0.07-1.3) had non IgE-mediated food allergy/food intolerance. CONCLUSIONS: By the age of 10 years, 6.8% of children suffered from FHS based on food challenges and a good clinical history. There was a large discrepancy between reported and diagnosed FHS. PMID- 26999748 TI - Chondroblastic osteosarcoma: Cytomorphologic characteristics and differential diagnosis on FNA. AB - BACKGROUND: Chondroblastic osteosarcoma (COS) is a uniformly fatal bone malignancy if not diagnosed and treated appropriately in a timely manner. Fine needle aspiration (FNA) of osseous lesions is routinely performed in major medical centers. Appropriate characterization of the tumor will significantly influence patient management and outcomes. METHODS: A retrospective review of the cytopathology archives of 2 large tertiary care centers for a 15-year period (2001-2015) revealed 17 cases of COS (9 primary, 6 recurrent, and 2 metastatic cases) in 16 patients. Clinical outcome and histopathologic follow-up were reviewed and correlated. RESULTS: There were 9 male and 7 female patients (male to-female ratio of approximately 1:1), ranging in age from 12 to 70 years (mean age, 29.2 years). The classic locations for osteosarcoma were commonly involved, such as the long bones around the region of the knee in 4 cases and the proximal humerus in 1 case. However, other "nonclassic" sites also were noted to be commonly involved, including the distal tibia or fibula (4 cases), sacroiliac region (4 cases), mandible (3 cases), and skull (1 case). Cytomorphologic characteristics were high cellularity; predominantly discohesive, single cells; small tissue fragments; background osteoid and chondroid matrix; spindled cells and plasmacytoid cells with moderate to abundant basophilic vacuolated cytoplasm and occasional multiple cytoplasmic processes; round to oval nuclei with anisonucleosis; and small to prominent nucleoli. There were scattered binucleated and multinucleated osteoclast-like giant cells. Cases with high-grade morphology demonstrated marked pleomorphism and abundant mitoses. CONCLUSIONS: The differential diagnosis of COS includes chondroblastoma, chondrosarcoma, and chondroid chordoma. A definitive diagnosis can be made with clinical and radiological correlation. Cancer Cytopathol 2016;124:493-500. (c) 2016 American Cancer Society. PMID- 26999750 TI - How physical alteration of technic materials affects mobility and phytoavailabilty of metals in urban soils? AB - One fundamental characteristic distinguishing urban soils from natural soils is the presence of technic materials or artefacts underlining the influence of human activity. These technic materials have different nature (organic or inorganic) and origins. They contribute to the enrichment of the soil solution by metallic trace elements. The present study aims to determine the effect of physical alteration of the technic coarse fraction on the bioavailability of metallic trace elements in urban Technosols. In general, results show that physical alteration increases the metallic trace elements water extractible concentrations of technic materials. The ability of lettuce to accumulate metallic trace elements, even at low concentrations, underlines the capacity of technic materials to contaminate the anthropised soil solution by bioavailable metals. The highest metal levels, accumulated by the various organs of the lettuce (leaves and roots), were measured in plants grown in presence of metallic particles mixtures. This indicates that the majority of metallic trace elements released by this technic constituent is bioavailable and explains the low plant biomass obtained. The abundant part of metallic trace elements released by the other technic constituents (building materials, bones, wood, plastic and fabric paper) remains less bioavailable. Under anthropised soil conditions, technic materials have a significant effect on the metallic trace elements behavior. They impact the flow of these metallic elements in Technosols, which can increase their bioavailability and, therefore, the contamination of the food chain. PMID- 26999749 TI - Cellulose-Enriched Microbial Communities from Leaf-Cutter Ant (Atta colombica) Refuse Dumps Vary in Taxonomic Composition and Degradation Ability. AB - Deconstruction of the cellulose in plant cell walls is critical for carbon flow through ecosystems and for the production of sustainable cellulosic biofuels. Our understanding of cellulose deconstruction is largely limited to the study of microbes in isolation, but in nature, this process is driven by microbes within complex communities. In Neotropical forests, microbes in leaf-cutter ant refuse dumps are important for carbon turnover. These dumps consist of decaying plant material and a diverse bacterial community, as shown here by electron microscopy. To study the portion of the community capable of cellulose degradation, we performed enrichments on cellulose using material from five Atta colombica refuse dumps. The ability of enriched communities to degrade cellulose varied significantly across refuse dumps. 16S rRNA gene amplicon sequencing of enriched samples identified that the community structure correlated with refuse dump and with degradation ability. Overall, samples were dominated by Bacteroidetes, Gammaproteobacteria, and Betaproteobacteria. Half of abundant operational taxonomic units (OTUs) across samples were classified within genera containing known cellulose degraders, including Acidovorax, the most abundant OTU detected across samples, which was positively correlated with cellulolytic ability. A representative Acidovorax strain was isolated, but did not grow on cellulose alone. Phenotypic and compositional analyses of enrichment cultures, such as those presented here, help link community composition with cellulolytic ability and provide insight into the complexity of community-based cellulose degradation. PMID- 26999752 TI - Roxarsone desorption from the surface of goethite by competitive anions, phosphate and hydroxide ions: Significance of the presence of metal ions. AB - Aromatic organoarsenical roxarsone (ROX) is a common additive for livestock feed. This arsenic containing pollutant could be discharged into the environment through agricultural application of animal manure, and pose potential threats to both humans and the wider environment. In this study, the influence of pH, competing anions and metal ions on the adsorption and desorption of ROX on goethite were investigated in order to understand their mobility in the environment. Both hydroxide ions and phosphate are common substances in the environment, and both are potential competing anions for ROX. Our results showed the addition of phosphate desorbed more ROX than the addition of hydroxide ions. As pH increased, the effect of phosphate did not show much difference to that of hydroxide ion. The results indicate that the presence of phosphate will greatly increase the mobility of ROX at low pH. Six common metal ions, including Zn(2+), Cu(2+), Fe(3+), Mn(2+), Mg(2+), and Ca(2+), were tested and all spiked metal ions enhanced the stability of ROX adsorption on the surface of goethite, and led to less desorption when phosphate was added. The results demonstrate that metal ions may form complex/surface precipitation with ROX to enhance its adsorption. The effect from Fe(3+), Zn(2+) and Cu(2+) was more pronounced than other metal ions, which might result from the fact that these three metal ions tend to associate with hydroxide ions and decrease the pH. The results of this research may shed light on the environmental fate and transportation of aromatic organoarsenicals in soil. PMID- 26999751 TI - High performance NiFe layered double hydroxide for methyl orange dye and Cr(VI) adsorption. AB - The NiFe layered double hydroxides (LDHs) with different mole ratio of Ni/Fe (4:1, 3:1, 7:3 and 1:1) were prepared by a simple coprecipitation method. The adsorption performance were evaluated by the removal of methyl orange (MO) dye and hexavalent chromium(VI) heavy metal ion. It is found that Ni4Fe1-LDH can remove more than 92% of MO in 10 min at the 10 mg/L MO initial concentration, and 97% of Cr(VI) in 1 h at 4 mg/L Cr2O7(2-) initial concentration. The saturated adsorption capacity of Ni4Fe1-LDH is found to be as large as 205.76 mg/g for MO and 26.78 mg/g for Cr(VI). The adsorption behavior of this new adsorbent is fitted well with Langmuir isotherm and the pseudo-second-order kinetic model, indicative of a monolayer and chemical adsorption that synergistically originates from exchangeable anions mechanism and layer charge density. Due to the excellent removal capacity of MO and Cr(VI), the NiFe-LDHs could be a promising adsorbent for wastewater treatment. PMID- 26999753 TI - Assessing multiple dimensions of urgency sensation: The University of South Australia Urinary Sensation Assessment (USA2 ). AB - AIMS: To develop and assess structure, test-retest reliability, and discriminative validity of a self-report questionnaire (University of South Australia Urinary Sensation Assessment: USA2 ) to assess multiple dimensions of urgency sensation. METHODS: The USA2 was designed and tested over two prospective, observational studies (2013-2014). Participants were English speaking Australians aged 50 or more with and without overactive bladder (OAB; determined by OAB awareness tool), recruited via health and recreation centers. In Study 1, exploratory factor analysis determined USA2 structure and subscales. In Study 2, confirmatory factor analysis reassessed structure; Mann-Whitney U tests determined discriminative validity (OAB vs. non-OAB for subscale and total scores) with Cohen's d effect sizes. Thirty-three individuals completed the USA2 twice; intraclass correlation coefficients (ICCs) and Wilcoxon signed rank tests assessed test-retest reliability. RESULTS: Questionnaires were returned by 189 eligible participants in Study 1 and 211 in Study 2. Exploratory factor analysis revealed three subscales: "urgency," "affective," "fullness." Confirmatory factor analysis supported these subscales. Subscale and total scores were significantly different between groups with and without OAB (P < 0.001). Cohen's d effect sizes (95%CI) were total score 1.8 (0.5-3.1), "urgency" subscale 1.8 (1.3-2.3), "affective" 1.7 (0.95-2.4), and "fullness" 0.75 (0.42-1.09). Total and subscales scores demonstrated test-retest reliability; ICCs (95%CIs) of 0.95 (0.9-0.98), 0.96 (0.92-0.98), 0.94 (0.88-0.97), and 0.78 (0.56-0.89). CONCLUSIONS: The USA2 assesses multiple dimensions of urgency sensation, is reliable over a 2-week period, and discriminates between older adults with and without OAB. Further validation is required in conditions other than overactive bladder. Neurourol. Urodynam. 36:667-672, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26999754 TI - Hemodynamic parameters in hypertensive diabetic patients. AB - OBJECTIVE: Despite adequate glycemic and blood pressure control, diabetic hypertensives remain at increased cardiovascular risk. Aortic stiffness and pulse pressure (PP) amplification may provide complementary information to correct cardiovascular risk. We aim to determine whether these hemodynamic parameters are interrelated or not and to explore the factors related to pressure pulsatility. METHODS: A cross-sectional study was conducted in 351 patients, involving controls, hypertensives without diabetes and diabetic patients with or without hypertension. Hemodynamic parameters were determined by applanation tonometry. Multivariate regression analyses evaluated the interest of therapeutic strategies. RESULTS: Aortic stiffness and PP amplification were not interrelated (P = 0.32) in multivariate-adjusted analysis and were both independently associated with previous cardiovascular events. Although disproportionately increased aortic stiffness in diabetic hypertensives (P < 0.001), no difference was found for PP amplification. The present dissociation between these two hemodynamic parameters may be related to the effect of increased heart rate (P < 0.001) in the presence of diabetes, in men and women. In diabetic hypertensives, aortic stiffness was correlated with glycated hemoglobin level (P = 0.04), but not with blood pressure or heart rate. Antihypertensive and statin treatments were correlated with PP amplification but not with aortic stiffness. CONCLUSION: Aortic stiffness and PP amplification were not interrelated, suggesting that these markers may provide complementary information for cardiovascular risk. New therapeutic strategies targeting pressure pulsatility should take into account the impact of hyperglycemia and increased heart rate in diabetic hypertensives. Gender influence on the role of autonomic nervous system in attenuating pressure wave reflections remains to be further established. PMID- 26999755 TI - Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells. AB - Kidney-specific drug targeting is an attractive strategy to reduce unwanted side effects and to enhance drug efficacy within the renal tissue. For this purpose a novel kidney-specific drug carrier was developed. The peptide sequence (KKEEE)3K triggers exceptional renal specificity at high accumulation rates. Micro-PET imaging studies of megalin-deficient mice indicate that the cellular endocytosis of this carrier is mediated by megalin. This assumption is supported by immunohistochemical analysis of FITC-labeled carrier peptide, which exclusively accumulated at the apical side of proximal tubule cells within the renal cortex. Scintigraphic studies of modified ciprofloxacin conjugated to (KKEEE)3K confirmed the excellent drug targeting potential of the peptide carrier. The conjugate accumulated entirely in the kidneys, revealing flawless redirection of ciprofloxacin, a compound that is mainly excreted by the liver. In conclusion, these results suggest the potential of (KKEEE)3K as a promising candidate for kidney-targeted drug delivery to proximal tubule cells. PMID- 26999756 TI - Electrochemical Characterization of Layer-By-Layer Assembled Ferrocene-Modified Linear Poly(ethylenimine)/Enzyme Bioanodes for Glucose Sensor and Biofuel Cell Applications. AB - Ferrocenylhexyl- and ferrocenylpropyl-modified linear poly(ethylenimine) (Fc-C6 LPEI, Fc-C3-LPEI) were used with periodate-modified glucose oxidase (p-GOX) in the layer-by-layer assembly of enzymatic bioanodes on gold. Fc-C6-LPEI/p-GOX and Fc-C3-LPEI/p-GOX films of 16 bilayers were capable of generating up to 381 +/- 3 and 1417 +/- 63 MUA cm(-2), respectively, in response to glucose. These responses are greater than those of analogous bioanodes fabricated using conventional cross linking techniques and are extremely high for planar, low surface area, single enzyme electrodes. (Fc-C3-LPEI/p-GOX)8 films generated 86 +/- 3 MUW cm(-2) at pH 7.0 and 149 +/- 7 MUW cm(-2) at pH 5.0, when poised against an air-breathing platinum cathode in a compartment-less biofuel cell. An increase in power output with decreasing pH was shown to be a result of increases in the platinum cathode performance, indicating it is the rate-limiting electrode in the biofuel cells. The effect of fabrication wash time on the buildup of material at the electrode's surface was probed using cyclic voltammetry (CV) and constant potential amperometry. The use of electrochemical techniques as a diagnostic tool for studying the material deposition process is discussed. CV peak separation (DeltaE), surface coverage of the electroactive ferrocene (GammaFc), and amperometric sensitivity of the enzyme to glucose (Jmax), studied as a function of numbers of bilayers, showed that physisorption of materials onto the surface results from initial patchy deposition, rather than in distinctly uniform layers. PMID- 26999758 TI - Accuracy of Wearable Devices for Estimating Total Energy Expenditure: Comparison With Metabolic Chamber and Doubly Labeled Water Method. PMID- 26999759 TI - Epigenetic status of H19/IGF2 and SNRPN imprinted genes in aborted and successfully derived embryonic stem cell lines in non-human primates. AB - The imprinted genes of primate embryonic stem cells (ESCs) often show altered DNA methylation. It is unknown whether these alterations emerge while deriving the ESCs. Here we studied the methylation patterns of two differentially methylated regions (DMRs), SNRPN and H19/IGF2 DMRs, during the derivation of monkey ESCs. We show that the SNRPN DMR is characteristically methylated at maternal alleles, whereas the H19/IGF2 DMR is globally highly methylated, with unusual methylation on the maternal alleles. These methylation patterns remain stable from the early stages of ESC derivation to late passages of monkey ESCs and following differentiation. Importantly, the methylation status of H19/IGF2 DMR and the expression levels of IGF2, H19, and DNMT3B mRNAs in early embryo-derived cells were correlated with their capacity to generate genuine ESC lines. Thus, we propose that these markers could be useful to predict the outcomes of establishing an ESC line in primates. PMID- 26999760 TI - Impact of transient down-regulation of DREAM in human embryonic stem cell pluripotency: The role of DREAM in the maintenance of hESCs. AB - Little is known about the functions of downstream regulatory element antagonist modulator (DREAM) in embryonic stem cells (ESCs). However, DREAM interacts with cAMP response element-binding protein (CREB) in a Ca(2+)-dependent manner, preventing CREB binding protein (CBP) recruitment. Furthermore, CREB and CBP are involved in maintaining ESC self-renewal and pluripotency. However, a previous knockout study revealed the protective function of DREAM depletion in brain aging degeneration and that aging is accompanied by a progressive decline in stem cells (SCs) function. Interestingly, we found that DREAM is expressed in different cell types, including human ESCs (hESCs), human adipose-derived stromal cells (hASCs), human bone marrow-derived stromal cells (hBMSCs), and human newborn foreskin fibroblasts (hFFs), and that transitory inhibition of DREAM in hESCs reduces their pluripotency, increasing differentiation. We stipulate that these changes are partly mediated by increased CREB transcriptional activity. Overall, our data indicates that DREAM acts in the regulation of hESC pluripotency and could be a target to promote or prevent differentiation in embryonic cells. PMID- 26999761 TI - Embryonic stem cell-derived neural progenitors transplanted to the hippocampus migrate on host vasculature. AB - This study describes the migration of transplanted ESNPs either injected directly into the hippocampus of a mouse, seeded onto hippocampal slices, or under in vitro culture conditions. We show that transplanted mouse ESNPs associate with, and appear to migrate on the surface of the vasculature, and that human ESNPs also associate with blood vessels when seeded on hippocampal slices, and migrate towards BECs in vitro using a Boyden chamber assay. This initial adhesion to vessels is mediated, at least in part, via the integrin alpha6beta1, as observed for SVZ neural progenitor cells. Our data are consistent with CXCL12, expressed by the astroglial-vasculature niche, playing an important role in the migration of transplanted neural progenitors within and outside of the hippocampus. PMID- 26999757 TI - Conversations for providers caring for patients with rectal cancer: Comparison of long-term patient-centered outcomes for patients with low rectal cancer facing ostomy or sphincter-sparing surgery. AB - For some patients with low rectal cancer, ostomy (with elimination into a pouch) may be the only realistic surgical option. However, some patients have a choice between ostomy and sphincter-sparing surgery. Sphincter-sparing surgery has been preferred over ostomy because it offers preservation of normal bowel function. However, this surgery can cause incontinence and bowel dysfunction. Increasingly, it has become evident that certain patients who are eligible for sphincter sparing surgery may not be well served by the surgery, and construction of an ostomy may be better. No validated assessment tool or decision aid has been published to help newly diagnosed patients decide between the two surgeries or to help physicians elicit long-term surgical outcomes. Furthermore, comparison of long-term outcomes and late effects after the two surgeries has not been synthesized. Therefore, this systematic review summarizes controlled studies that compared long-term survivorship outcomes between these two surgical groups. The goals are: 1) to improve understanding and shared decision-making among surgeons, oncologists, primary care providers, patients, and caregivers; 2) to increase the patient's participation in the decision; 3) to alert the primary care provider to patient challenges that could be addressed by provider attention and intervention; and 4) ultimately, to improve patients' long-term quality of life. This report includes discussion points for health care providers to use with their patients during initial discussions of ostomy and sphincter-sparing surgery as well as questions to ask during follow-up examinations to ascertain any long term challenges facing the patient. CA Cancer J Clin 2016;66:387-397. (c) 2016 American Cancer Society. PMID- 26999762 TI - Program Director Opinion on the Ideal Length of Residency Training in Emergency Medicine. AB - OBJECTIVE: This study sought to define expert opinion on the ideal length of training (LoT) for Accreditation Council of Graduate Medical Education (ACGME) accredited emergency medicine (EM) residency programs. METHODS: A cross-sectional Web-based survey was sent to program directors (PDs) at all ACGME-accredited EM residency programs during a study period of August to October 2014. The primary outcome of ideal LoT was determined in two ways: 1) subjects provided the ideal total LoT in months and 2) then separately selected the type and number of rotations for an ideal EM residency curriculum by month, the sum of which provided an alternative measurement of their ideal LoT. We did not include vacation time. Descriptive statistics and an analysis of variance are reported. RESULTS: Response rate was 68.0% (108/159) with 72% of respondents (78/108) directing programs in the PGY 1-3 (36-month) format and 28% directing PGY 1-4 (48 month) programs. More than half of subjects (51.9%) have direct personal experience with both formats. When asked about ideal total LoT, PDs averaged 41.5 months (n = 107; SD = 5.5 months, range = 36-60 months). When asked to provide durations of individual clinical experiences for their ideal EM program, the sum total (n = 104) averaged 45.0 months. Results from a factorial analysis of variance revealed statistically significant effects of PDs' past training experiences: participants who trained in a 36-month program had statistically significantly lower LoT (mean = 39.2 months) than participants who trained in a 48-month program (mean = 44.5 months). There was also a statistically significant effect of current program format on ideal LoT: participants who directed a 36 month program had statistically significantly lower LoT (mean = 39.8 months) than participants who directed a 48-month program (mean = 45.8 months). CONCLUSIONS: PD opinion on ideal LoT averages between 36 and 48 months, but is longer when the sum of desired clinical rotations is considered. While half of the respondents reported direct experience with both PGY 1-3 and PGY 1-4 training programs, opinions on ideal LoT through both methods corresponded strongly with the length of the program the PDs trained in and the format of the program they currently direct. PD opinions may be too biased by their own experiences to provide objective input on the ideal LoT for EM residency programs. PMID- 26999764 TI - The type of loose seton for complex anal fistula is essential to improve perianal comfort and quality of life. AB - AIM: The use of a loose seton for complex anal fistulae can cause perianal discomfort and reduced quality of life. The aim of this study was to assess the impact of the novel knot-free Comfort Drain on quality of life, perianal comfort and faecal continence compared to conventional loose setons. METHOD: Forty-four patients treated for complex anal fistula at a single institution between July 2013 and September 2014 were included in the study. A matched-pair analysis was performed to compare patients with a knot-free Comfort Drain and controls who were managed by conventional knotted setons. The 12-item Short Form survey (SF 12) questionnaire was used to assess quality of life. Additionally, patients reported perianal comfort and faecal incontinence using a Visual Analog Scale (VAS) and the St Mark's Incontinence Score. RESULTS: The Comfort Drain was associated with improved quality of life with significant higher median physical (P = 0.001) and mental (P = 0.04) health scores compared with a conventional loose seton. According to the VAS, patients with a Comfort Drain in situ reported greater perianal comfort with significantly less burning sensation (P < 0.001) and pruritus (P < 0.001). Faecal continence was similar in each group. CONCLUSION: The Comfort Drain offers improved perianal comfort and better quality of life compared with a conventional loose seton and therefore facilitates long term therapy in patients with complex fistula-in-ano. PMID- 26999765 TI - Antipsychotics and Increased Mortality: Are We Sure? PMID- 26999763 TI - Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells. AB - Antigen uptake by dendritic cells and intracellular routing of antigens to specific compartments is regulated by C-type lectin receptors that recognize glycan structures. We show that the modification of Ovalbumin (OVA) with the glycan-structure Lewis(X) (Le(X)) re-directs OVA to the C-type lectin receptor MGL1. Le(X)-modification of OVA favored Th1 skewing of CD4(+) T cells and enhanced cross-priming of CD8(+) T cells. While cross-presentation of native OVA requires high antigen dose and TLR stimuli, Le(X) modification reduces the required amount 100-fold and obviates its dependence on TLR signaling. The OVA Le(X)-induced enhancement of T cell cross-priming is MGL1-dependent as shown by reduced CD8(+) effector T cell frequencies in MGL1-deficient mice. Moreover, MGL1 mediated cross-presentation of OVA-Le(X) neither required TAP-transporters nor Cathepsin-S and was still observed after prolonged intracellular storage of antigen in Rab11(+)LAMP1(+) compartments. We conclude that controlled neo glycosylation of antigens can crucially influence intracellular routing of antigens, the nature and strength of immune responses and should be considered for optimizing current vaccination strategies. PMID- 26999766 TI - Cognitive profile of young well-trained athletes with intellectual disabilities. AB - BACKGROUND: Previous research has shown that cognitive and motor skills are related. The precise impact of cognitive impairment on sport proficiency, however, is unknown. AIMS: This study investigated group and individual differences in cognitive profiles in a large cohort of track and field athletes, basketball players, swimmers and table tennis players with (N=468) and without (N=162) intellectual disabilities (ID). METHODS AND PROCEDURES: Based on the Cattell-Horn-Carroll Theory of Cognitive abilities, eight subtests were selected for inclusion in a generic cognitive test (GCT) to assess executive functions and cognitive abilities relevant to sport, i.e., fluid reasoning, visual processing, reaction and decision speed, short-term memory and processing speed. OUTCOMES AND RESULTS: Reliability coefficients for the subtests ranged between 0.25 and 0.88 respectively. Factor analysis revealed two clusters of subtests, i.e., a speed based factor (simple and complex reaction time and simple and complex visual search) and a performance-based factor (Corsi Memory, Tower of London, WASI Block Design and Matrix Reasoning). After controlling for psychomotor speed, the group of ID-athletes scored significantly lower than athletes without ID on all the GCT subtests, except the complex visual search test. When cognitive profiles of individual ID- athletes were examined, some obtained higher scores than the average norm values in the reference population. CONCLUSIONS AND IMPLICATIONS: The GCT is currently administered as part of the classification process for athletes with ID who compete in the Paralympic Games. The results of this study indicate that the complex visual search and Tower of London test in the GCT should be reconsidered. PMID- 26999767 TI - Neuropsychiatric manifestations in inflammatory neuropathies: A systematic review. AB - We conducted a systematic literature review on psychological and behavioral comorbidities in patients with inflammatory neuropathies. In Guillain-Barre syndrome (GBS), psychotic symptoms are reported during early stages in 30% of patients. Typical associations include mechanical ventilation, autonomic dysfunction, inability to communicate, and severe weakness. Anxiety and depression are frequent comorbidities. Anxiety may increase post-hospital admissions and be a predictor of mechanical ventilation. Posttraumatic stress disorder may affect up to 20% of ventilated patients. Sleep disturbances are common in early-stage GBS, affecting up to 50% of patients. In chronic inflammatory demyelinating polyradiculoneuropathy, memory and quality of sleep may be impaired. An independent link between depression and pretreatment upper limb disability and ascites was reported in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin) syndrome, with an association with early death. Hematological treatment of POEMS appears effective on depression. Published literature on psychological/behavioral manifestations in inflammatory neuropathies remains scarce, and further research is needed. Muscle Nerve 54: 1 8, 2016. PMID- 26999768 TI - Contamination of commonly consumed raw vegetables with soil transmitted helminth eggs in Mazandaran province, northern Iran. AB - Soil-transmitted helminth (STH) infections are responsible for significant burden of morbidity and mortality worldwide. Consumption of raw vegetables without proper washing is one of the major routes of such infections. We evaluate the prevalence of STH contamination in commonly used vegetables in Mazandaran province, northern Iran. A total of 772 fresh raw vegetables were obtained from retail markets. Each sample was divided into two groups. One group was used as the unwashed sample and the second group was washed with standard washing procedures. Then, samples were examined for helminth eggs by using standard methods. Data analysis was performed using SPSS20. The overall prevalence of STHs was 14.89% (115/772). The rate of STH contamination was significantly higher in warm seasons (20.5%, 79/386) than in cold seasons (9.32%, 36/386) among the unwashed vegetables (OR=2.50; CI 95%=1.64-3.8; P<0.001). No parasites were observed in standard washed samples (OR=271.40; CI 95%=16.84-4373.64; P<0.001). Prevalence of STH contamination was significantly higher in leafy vegetables than root vegetables (OR=1.67; CI 95%=1.09-2.55; P<0.05). The prevalence of STHs species in all the vegetables were as follows: Ascaris lumbricoides (3.36%), Trichuris trichiura (2.2%), hookworms (2.9%), Toxocara spp. (1.68%), Trichostrongylus spp. (1.55), Taenia sp. (0.9%) and Hymenolepis nana (2.2%). The results of the present study emphasized that vegetables are potential risk factor for transmission of helminth infection to human in northern Iran. It is necessary that health authorities trained the consumers to proper and standard washing of vegetables before consumption. PMID- 26999769 TI - Rapid and sensitive monitoring of biocatalytic reactions using ion mobility mass spectrometry. AB - The combination of stable isotope labelling with direct infusion ion mobility mass spectrometry (IM-MS) enabled qualitative and quantitative monitoring of biocatalytic reactions with reduced analysis times, enhanced sensitivity and MUL level assay volumes. The new approach was demonstrated by applying to both lipase and monooxygenase enzymes, including multi-substrate screening. PMID- 26999770 TI - Genotype-guided antiretroviral regimens in children with multidrug-resistant HIV 1 infection. AB - BACKGROUND: Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low- and middle-income countries. METHODS: Sixteen children with antiretroviral therapy (ART) failure and triple class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data. The primary end point was virological suppression (<50 copies/ml) and immunological improvement after 48 wk of treatment with the new ART regimen. RESULTS: The median age of the patients was 14.5 y (interquartile range (IQR) 11-16.5). Median HIV-1 RNA viral load was 4.2 log10 (IQR: 3.4-4.8). The primary end point was found in 11 children (69%), and 13 children (81%) had an HIV-1 RNA viral load <200 copies/ml. Median (IQR) for the baseline CD4(+) cell count was 382 cells/MUl (281-686 cells/MUl), whereas after 48 wk of treatment with the new ART regimen, it was 640 cells/MUl (361-936 cells/MUl) (P < 0.001). CONCLUSION: Darunavir/ritonavir, raltegravir, and etravirine were well tolerated in the present pediatric population. These drugs provide good options for children exposed to extensive ART. Regimens guided by genotyping data were effective for children who had ART failure and multidrug resistant HIV-1 infection. PMID- 26999771 TI - Ethical Issues in the Use of Extracorporeal Membrane Oxygenation in Controlled Donation After Circulatory Determination of Death. AB - The use of donor extracorporeal membrane oxygenation (ECMO) to improve graft outcomes by some controlled donation after circulatory determination of death (cDCDD) programs raises ethical issues. We reviewed cDCDD protocols using ECMO and the relevant ethics literature to analyze these issues. It is not obvious that ECMO in cDCDD improves graft outcomes. In our opinion, ECMO implemented before death can interfere with end-of-life care and damage bodily integrity. By restoring systemic circulation, ECMO risks invalidating the preceding declaration of death if brain and cardiac perfusion is not adequately excluded because of malfunction or misplacement of the supradiaphragmatic aortic occlusion balloon. The use of ECMO is not compatible with the acronym DCDD because circulation is restored after the determination of death. Because of these deficiencies, we concluded that other techniques are preferable, such as rapid recovery or in situ cold infusion. If ECMO is performed, it requires a specific informed consent and transparency. PMID- 26999772 TI - The causal role of human papillomavirus infections in non-anogenital cancers. It's time to ask for the functional evidence. PMID- 26999774 TI - Novel application of X-ray fluorescence microscopy (XFM) for the non-destructive micro-elemental analysis of natural mineral pigments on Aboriginal Australian objects. AB - This manuscript presents the first non-destructive synchrotron micro-X-ray fluorescence study of natural mineral pigments on Aboriginal Australian objects. Our results demonstrate the advantage of XFM (X-ray fluorescence microscopy) of Aboriginal Australian objects for optimum sensitivity, elemental analysis, micron resolution mapping of pigment areas and the method also has the advantage of being non-destructive to the cultural heritage objects. Estimates of pigment thickness can be calculated. In addition, based on the elemental maps of the pigments, further conclusions can be drawn on the composition and mixtures and uses of natural mineral pigments and whether the objects were made using traditional or modern methods and materials. This manuscript highlights the results of this first application of XFM to investigate complex mineral pigments used on Aboriginal Australian objects. PMID- 26999773 TI - Investigating the Role of Physical Education in Physical Activity Promotion: An Italian Multicenter Study. AB - BACKGROUND: Physical education (PE) can be considered an instrument for active lifestyle promotion, and PE teachers can motivate youths to continue their studies in the field of Movement Sciences (MS). METHODS: To evaluate the role of PE in higher secondary school in promoting physical activity (PA) and MS careers, previous PE experiences and current PA practice were investigated in a sample of Italian freshmen enrolled in different university degree courses. RESULTS: A total of 7033 questionnaires were completed by students from 14 universities (41.3% males, mean age 20 +/- 2.76 years). Recreation seemed to be the principal aim (42.2%) pursued during PE lessons, which are based mainly on practical activities (51.7%). Of all respondents, 67.2% were satisfied with the PE received during higher secondary school, and 51.6% participated in extracurricular PA. Current practice of PA was reported by 58.1% of the sample. Extracurricular activities were associated with choice of MS curricula (odds ratio: 2.15; 95% confidence interval, 1.85-2.50) and with current practice of PA (odds ratio: 1.68, 95% confidence interval, 1.51-1.87). Geographical differences concerning lessons organization and satisfaction were registered (P < .01). CONCLUSIONS: To enhance its role in health promotion, PE teaching should be improved by increasing the time allocated to PE and by strengthening the provision of school based extracurricular PA. PMID- 26999775 TI - Navigating the geography of mortality--towards a GPS for Public Health Policy. PMID- 26999776 TI - Acquired Syphilis With Anemia and Leukoerythroblastic Reaction: A Case Report. PMID- 26999777 TI - Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome. AB - Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, Dz', which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome. PMID- 26999779 TI - Why Does the Intramolecular Trimethylene-Bridged Frustrated Lewis Pair Mes2 PCH2 CH2 CH2 B(C6 F5 )2 Not Activate Dihydrogen? AB - The methyl labelled C3 -bridged frustrated phosphane borane Lewis pair (P/B FLP) 2 b was prepared by treatment of Mes2 PCl with a methallyl Grignard reagent followed by anti-Markovnikov hydroboration with Piers' borane [HB(C6 F5 )2 )]. The FLP 2 b is inactive toward dihydrogen under typical ambient conditions, in contrast to the C2 - and C4 -bridged FLP analogues. Dynamic NMR spectroscopy showed that this was not due to kinetically hindered P???B dissociation of 2 b. DFT calculations showed that the hydrogen-splitting reaction of the parent compound 2 a is markedly endergonic. The PH(+) /BH(-) H2 -splitting product of 2 b was indirectly synthesized by a sequence of H(+) /H(-) addition. It lost H2 at ambient conditions and confirmed the result of the DFT analysis. PMID- 26999778 TI - A salvage chemotherapy of R-P-IMVP16/CBDCA consisting of rituximab, methylprednisolone, ifosfamide, methotrexate, etoposide, and carboplatin for patients with diffuse large B cell lymphoma who had previously received R-CHOP therapy as first-line chemotherapy. AB - We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R-CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m2 on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m2 for 5 days (from day 3 to day 7), methotrexate 30 mg/m2 on day 5 and day 12, etoposide 80 mg/m2 for 3 days (from day 3 to day 5), and carboplatin 300 mg/m2 on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2-year overall survival rate was 55.3%. The 2-year progression free survival rate was 34.7%. The 2-year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p < 0.0001). One patient died because of sepsis related to the treatment regimen. Non hematological adverse effects were mild and tolerable. The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999780 TI - Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis. AB - Biosynthesis enables renewable production of manifold compounds, yet often biosynthetic performance must be improved for it to be economically feasible. Nongenetic, cell-to-cell variations in protein and metabolite concentrations are naturally inherent, suggesting the existence of both high- and low-performance variants in all cultures. Although having an intrinsic source of low performers might cause suboptimal ensemble biosynthesis, the existence of high performers suggests an avenue for performance enhancement. Here we develop in vivo population quality control (PopQC) to continuously select for high-performing, nongenetic variants. We apply PopQC to two biosynthetic pathways using two alternative design principles and demonstrate threefold enhanced production of both free fatty acid (FFA) and tyrosine. We confirm that PopQC improves ensemble biosynthesis by selecting for nongenetic high performers. Additionally, we use PopQC in fed-batch FFA production and achieve 21.5 g l(-1) titer and 0.5 g l(-1) h(-1) productivity. Given the ubiquity of nongenetic variation, PopQC should be applicable to a variety of metabolic pathways for enhanced biosynthesis. PMID- 26999781 TI - Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage. AB - The critical cellular hydride donor NADPH is produced through various means, including the oxidative pentose phosphate pathway (oxPPP), folate metabolism and malic enzyme. In growing cells, it is efficient to produce NADPH via the oxPPP and folate metabolism, which also make nucleotide precursors. In nonproliferating adipocytes, a metabolic cycle involving malic enzyme holds the potential to make both NADPH and two-carbon units for fat synthesis. Recently developed deuterium ((2)H) tracer methods have enabled direct measurement of NADPH production by the oxPPP and folate metabolism. Here we enable tracking of NADPH production by malic enzyme with [2,2,3,3-(2)H]dimethyl-succinate and [4-(2)H]glucose. Using these tracers, we show that most NADPH in differentiating 3T3-L1 mouse adipocytes is made by malic enzyme. The associated metabolic cycle is disrupted by hypoxia, which switches the main adipocyte NADPH source to the oxPPP. Thus, (2)H-labeled tracers enable dissection of NADPH production routes across cell types and environmental conditions. PMID- 26999782 TI - Steric trapping reveals a cooperativity network in the intramembrane protease GlpG. AB - Membrane proteins are assembled through balanced interactions among proteins, lipids and water. Studying their folding while maintaining the native lipid environment is necessary but challenging. Here we present methods for analyzing key elements of membrane protein folding including thermodynamic stability, compactness of the unfolded state and folding cooperativity under native conditions. The methods are based on steric trapping, which couples the unfolding of a doubly biotinylated protein to the binding of monovalent streptavidin (mSA). We further advanced this technology for general application by developing versatile biotin probes possessing spectroscopic reporters that are sensitized by mSA binding or protein unfolding. By applying these methods to the Escherichia coli intramembrane protease GlpG, we elucidated a widely unraveled unfolded state, subglobal unfolding of the region encompassing the active site, and a network of cooperative and localized interactions to maintain stability. These findings provide crucial insights into the folding energy landscape of membrane proteins. PMID- 26999783 TI - Transcriptional Analysis and Subcellular Protein Localization Reveal Specific Features of the Essential WalKR System in Staphylococcus aureus. AB - The WalKR two-component system, controlling cell wall metabolism, is highly conserved among Bacilli and essential for cell viability. In Staphylococcus aureus, walR and walK are followed by three genes of unknown function: walH, walI and walJ. Sequence analysis and transcript mapping revealed a unique genetic structure for this locus in S. aureus: the last gene of the locus, walJ, is transcribed independently, whereas transcription of the tetra-cistronic walRKHI operon occurred from two independent promoters located upstream from walR. Protein topology analysis and protein-protein interactions in E. coli as well as subcellular localization in S. aureus allowed us to show that WalH and WalI are membrane-bound proteins, which associate with WalK to form a complex at the cell division septum. While these interactions suggest that WalH and WalI play a role in activity of the WalKR regulatory pathway, deletion of walH and/or walI did not have a major effect on genes whose expression is strongly dependent on WalKR or on associated phenotypes. No effect of WalH or WalI was seen on tightly controlled WalKR regulon genes such as sle1 or saouhsc_00773, which encodes a CHAP-domain amidase. Of the genes encoding the two major S. aureus autolysins, AtlA and Sle1, only transcription of atlA was increased in the DeltawalH or DeltawalI mutants. Likewise, bacterial autolysis was not increased in the absence of WalH and/or WalI and biofilm formation was lowered rather than increased. Our results suggest that contrary to their major role as WalK inhibitors in B. subtilis, the WalH and WalI proteins have evolved a different function in S. aureus, where they are more accessory. A phylogenomic analysis shows a striking conservation of the 5 gene wal cluster along the evolutionary history of Bacilli, supporting the key importance of this signal transduction system, and indicating that the walH and walI genes were lost in the ancestor of Streptococcaceae, leading to their atypical 3 wal gene cluster, walRKJ. PMID- 26999785 TI - Amplified fluorescence detection of adenosine via catalyzed hairpin assembly and host-guest interactions between beta-cyclodextrin polymer and pyrene. AB - Nowadays, enzyme-free nucleic acid-based signal amplification strategies are frequently utilized in the design of biosensors due to their excellent sensitivity. Developing more extended analytical methods is fundamental for basic studies in the biological and biomedical fields. Herein, we introduce an enzyme free amplified detection strategy for the small molecule adenosine. The approach is based on adenosine-aptamer binding triggered catalyzed hairpin assembly and host-guest interactions between beta-cyclodextrin polymer (beta-CDP) and pyrene. Two hairpin probes (probe H1 and probe H2) and an aptamer-trigger/inhibitor duplex probe were employed in the system and the pyrene-labeled probe H1 was chosen as the signal unit. In the absence of adenosine, the aptamer-trigger was inhibited by the inhibitor strand. The hairpin probes were in the closed hairpin formation without activation of the trigger strand. Pyrene labeled at the 5' termini of the single-stranded stem of probe H1 could be easily trapped in the hydrophobic cavity of beta-CDP because of weak steric hindrance, leading to a significant fluorescence enhancement. Once the hairpin assembly was catalyzed by the adenosine-aptamer binding event, a hybridized DNA duplex H1/H2 was created continuously. Pyrene labeled at the 5'-termini of the DNA duplex H1/H2 finds it difficult to enter the cavity of beta-CDP due to steric hindrance, leading to a weaker fluorescence signal. Thus, the target could be detected by this simple mix and-detect amplification method without a need for expensive and perishable protein enzymes. As low as 42 nM of adenosine was detected by this assay, which is comparable to that of some reported colorimetric methods. Meanwhile, the proposed method was further successfully applied to detect adenosine in human serum samples, showing great potential for adenosine detection from complex fluids. PMID- 26999784 TI - Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium. AB - BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. METHODS: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. RESULTS: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04). CONCLUSIONS: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF. PMID- 26999786 TI - Q787Q EGFR Polymorphism as a Prognostic Factor for Lung Squamous Cell Carcinoma. AB - OBJECTIVE: EGFR genetic polymorphisms have been investigated for carcinogenesis in various tumors including lung cancer. We evaluated EGFR mutations in four exons, with an emphasis on the Q787Q EGFR polymorphism in non-small-cell lung cancer. METHODS: To determine the presence of the Q787Q polymorphism in patients with lung cancer, we performed direct sequencing analyses of four exons for 83 squamous cell carcinomas and 80 adenocarcinomas untreated with EGFR tyrosine kinase inhibitors. RESULTS: The Q787Q EGFR polymorphism was more frequently detected in squamous cell carcinoma patients than in adenocarcinoma patients (24 vs. 15.9%). The group of patients with the Q787Q EGFR polymorphism included more males and heavy smokers compared with other patient groups. The presence of the Q787Q EGFR polymorphism significantly and negatively affected the overall survival rate among patients with non-small-cell carcinoma (p = 0.011), particularly those with squamous cell carcinoma (p = 0.037). Among stage I and II squamous cell carcinoma patients, those with the Q787Q EGFR polymorphism had a poor prognosis (p = 0.032). CONCLUSIONS: The Q787Q EGFR polymorphism allows stratifying lung squamous cell carcinoma patients and could be an independent prognostic marker, particularly among those in stages I and II. PMID- 26999787 TI - Revisiting the Role of Potassium Sensitivity Testing and Cystoscopic Hydrodistention for the Diagnosis of Interstitial Cystitis. AB - OBJECTIVES: To revisit the diagnostic roles of cystoscopic hydrodistention and the potassium sensitivity test (PST) for the diagnosis of interstitial cystitis (IC). METHODS: We prospectively enrolled 214 patients clinically diagnosed with IC, 125 non-IC patients who underwent video urodynamic studies and PST, and another 144 non-IC patients who underwent cystoscopic hydrodistention before transurethral surgery. The sensitivity, specificity, and positive and negative predictive values were calculated for the PST and glomerulations after cystoscopic hydrodistention. RESULTS: After cystoscopic hydrodistention, glomerulations developed in 211/214 (98.6%) IC patients and 61/144 (42.4%) of the non-IC patients including patients with stones (45/67, 67%), hematuria (2/5, 40%), and stress urinary incontinence (SUI) (6/17, 35%). When positive glomerulation was defined as grade 2 or more, the sensitivity was 61.7%. The PST was positive in 183/214 (85.5%) IC patients and 7/17 (41%) with hypersensitive bladder, 7/32 (22%) with detrusor overactivity, 5/27 (18%) with SUI, 2/21 (10%) with lower urinary tract symptoms, and 2/25 (8%) with bladder outlet obstruction. The PST had a sensitivity of 85.5% and a specificity of 81.6% for diagnosis of IC. IC patients with a positive PST had a significantly smaller urgency sensation capacity, smaller voided volume, and greater bladder pain score. CONCLUSIONS: Both the PST and glomerulations after hydrodistention are sensitive indicators of IC, but the specificity of glomerulations in the diagnosis of IC is lower than that of the PST. A positive PST is associated with a more hypersensitive bladder and bladder pain, but not the grade of glomerulations in IC patients. Neither test provided 100% diagnostic accuracy for IC, we might select patients into different subgroups based on different PST and hydrodistention results, not for making a diagnosis of IC but for guidance of different treatments. PMID- 26999790 TI - The phenotypic characterization of yeast strains to stresses inherent to wine fermentation in warm climates. AB - AIMS: Climate change is exerting an increasingly profound effect on grape composition, microbiology, chemistry and the sensory aspects of wine. Identification of autochthonous yeasts tolerant to stress could help to alleviate this effect. METHODS AND RESULTS: Tolerance to osmotic pressure, ethanol and pH of 94 Saccharomyces cerevisiae strains and 29 strains non-Saccharomyces from the warm climate region DO 'Vinos de Madrid' (Spain) using phenotypic microarray and their fermentative behaviour were studied. The screening highlighted 12 strains of S. cerevisiae isolated from organic cellars with improved tolerance to osmotic stress, high ethanol concentrations and suitable fermentative properties. Screening of non-Saccharomyces spp. such as Lanchacea thermotolerans, Torulaspora delbrueckii, Schizosaccharomyces pombe and Mestchnikowia pulcherrima also highlighted tolerance to these stress conditions. CONCLUSIONS: This study confirmed the adaptation of native strains to the climatic conditions in each area of production and correlated these adaptations with good fermentation properties. Screening has revealed that identifying yeast strains adapted to fermentation stresses is an important approach for making quality wines in very warm areas. SIGNIFICANCE AND IMPACT OF THE STUDY: The results have special relevance because it is a pioneering study that has approached the problem of climate change for wines from a microbiological aspect and has analysed the situation in situ in wineries from a warm climate zone. Resistant strains were found with good biological properties; studying these strains for their stress response mechanisms during fermentation will be of interest to the wine making industry. PMID- 26999788 TI - Potential Sources and Transmission of Salmonella and Antimicrobial Resistance in Kampala, Uganda. AB - In sub-Saharan Africa, non-typhoidal Salmonellae (NTS) cause invasive disease particularly in children and HIV infected adults, but the disease epidemiology is poorly understood. Between 2012 and 2013, we investigated NTS sources and transmission in Kampala. We detected Salmonella in 60% of the influent and 60% of the effluent samples from a wastewater treatment plant and 53.3% of the influent and 10% of the effluent samples from waste stabilization ponds that serve the human population; 40.9% of flush-water samples from ruminant slaughterhouses, 6.6% of the poultry fecal samples from live bird markets and 4% of the fecal samples from swine at slaughter; and in 54.2% of the water samples from a channel that drains storm-water and effluents from the city. We obtained 775 Salmonella isolates, identified 32 serovars, and determined resistance to 15 antimicrobials. We genotyped common serovars using multiple-locus variable number tandem repeats analysis or pulsed-field gel electrophoresis. In addition, we analyzed 49 archived NTS isolates from asymptomatic livestock and human clinical cases. Salmonella from ruminant and swine sources were mostly pan-susceptible (95%) while poultry isolates were generally more resistant. Salmonella Kentucky isolated from poultry exhibited extensive drug resistance characterized by resistance to 10 antimicrobials. Interestingly, similar genotypes of S. Kentucky but with less antimicrobial resistance (AMR) were found in poultry, human and environmental sources. The observed AMR patterns could be attributed to host or management factors associated with production. Alternatively, S. Kentucky may be prone to acquiring AMR. The factors driving AMR remain poorly understood and should be elucidated. Overall, shared genotypes and AMR phenotypes were found in NTS from human, livestock and environmental sources, suggesting zoonotic and environmental transmissions most likely occur. Information from this study could be used to control NTS transmission. PMID- 26999789 TI - Structure, Properties, and In Vitro Behavior of Heat-Treated Calcium Sulfate Scaffolds Fabricated by 3D Printing. AB - The ability of inkjet-based 3D printing (3DP) to fabricate biocompatible ceramics has made it one of the most favorable techniques to generate bone tissue engineering (BTE) scaffolds. Calcium sulfates exhibit various beneficial characteristics, and they can be used as a promising biomaterial in BTE. However, low mechanical performance caused by the brittle character of ceramic materials is the main weakness of 3DP calcium sulfate scaffolds. Moreover, the presence of certain organic matters in the starting powder and binder solution causes products to have high toxicity levels. A post-processing treatment is usually employed to improve the physical, chemical, and biological behaviors of the printed scaffolds. In this study, the effects of heat treatment on the structural, mechanical, and physical characteristics of 3DP calcium sulfate prototypes were investigated. Different microscopy and spectroscopy methods were employed to characterize the printed prototypes. The in vitro cytotoxicity of the specimens was also evaluated before and after heat treatment. Results showed that the as-printed scaffolds and specimens heat treated at 300 degrees C exhibited severe toxicity in vitro but had almost adequate strength. By contrast, the specimens heat treated in the 500 degrees C-1000 degrees C temperature range, although non-toxic, had insufficient mechanical strength, which was mainly attributed to the exit of the organic binder before 500 degrees C and the absence of sufficient densification below 1000 degrees C. The sintering process was accelerated at temperatures higher than 1000 degrees C, resulting in higher compressive strength and less cytotoxicity. An anhydrous form of calcium sulfate was the only crystalline phase existing in the samples heated at 500 degrees C 1150 degrees C. The formation of calcium oxide caused by partial decomposition of calcium sulfate was observed in the specimens heat treated at temperatures higher than 1200 degrees C. Although considerable improvements in cell viability of heat treated scaffolds were observed in this study, the mechanical properties were not significantly improved, requiring further investigations. However, the findings of this study give a better insight into the complex nature of the problem in the fabrication of synthetic bone grafts and scaffolds via post-fabrication treatment of 3DP calcium sulfate prototypes. PMID- 26999791 TI - Abundance and Distribution of Sperm Whales in the Canary Islands: Can Sperm Whales in the Archipelago Sustain the Current Level of Ship-Strike Mortalities? AB - Sperm whales are present in the Canary Islands year-round, suggesting that the archipelago is an important area for this species in the North Atlantic. However, the area experiences one of the highest reported rates of sperm whale ship-strike in the world. Here we investigate if the number of sperm whales found in the archipelago can sustain the current rate of ship-strike mortality. The results of this study may also have implications for offshore areas where concentrations of sperm whales may coincide with high densities of ship traffic, but where ship strikes may be undocumented. The absolute abundance of sperm whales in an area of 52933 km2, covering the territorial waters of the Canary Islands, was estimated from 2668 km of acoustic line-transect survey using Distance sampling analysis. Data on sperm whale diving and acoustic behaviour, obtained from bio-logging, were used to calculate g(0) = 0.92, this is less than one because of occasional extended periods when whales do not echolocate. This resulted in an absolute abundance estimate of 224 sperm whales (95% log-normal CI 120-418) within the survey area. The recruitment capability of this number of whales, some 2.5 whales per year, is likely to be exceeded by the current ship-strike mortality rate. Furthermore, we found areas of higher whale density within the archipelago, many coincident with those previously described, suggesting that these are important habitats for females and immature animals inhabiting the archipelago. Some of these areas are crossed by active shipping lanes increasing the risk of ship strikes. Given the philopatry in female sperm whales, replacement of impacted whales might be limited. Therefore, the application of mitigation measures to reduce the ship-strike mortality rate seems essential for the conservation of sperm whales in the Canary Islands. PMID- 26999792 TI - Non-immediate hypersensitivity reactions to beta-lactam antibiotics in children - our 10-year experience in allergy work-up. AB - BACKGROUND: Non-immediate reactions to beta-lactam antibiotics (BL) occur more than one hour after drug administration, and the most common manifestations are maculopapular exanthemas and delayed-appearing urticaria and/or angioedema. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions (DHR), if a drug is taken at the same time. The most of children are labeled as 'drug allergic' after considering only the clinical history. OBJECTIVE: To diagnose/detect a hypersensitivity or an infection which mimic DHR in children with non-immediate reactions to BL METHODS: A prospective survey was conducted in a group of 1026 children with histories of non-immediate reactions to BL by performing patch tests, skin tests, and in case of negative results, drug provocation tests (DPTs). In 300 children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. RESULTS: Urticaria and maculopapular exanthemas were the most reported non-immediate reactions. Only 76 (7.4%) of 1026 children had confirmed non-immediate hypersensitivity reactions to BL. Fifty-seven children had positive delayed-reading intradermal tests (18 of these with a positive patch test). Nineteen children had positive DPT. Sixty-six of 300 children had positive tests for viruses or Mycoplasma pneumoniae and 2 of them had a positive allergy work-up. CONCLUSIONS: A diagnostic work-up should be performed in all children with non-immediate reactions to BL, to remove a false label of hypersensitivity. Even though only 57 (5.5%) of 1026 children displayed positive responses to delayed-reading intradermal tests to BL, such tests appear to be useful in order to reduce the risk for positive DPTs. PMID- 26999793 TI - Reduced goal-directed action control in autism spectrum disorder. AB - Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental conditions associated with persistent, stereotyped or repetitive actions, and patterns of interest that are maintained in spite of possible negative outcomes. The aim of the present study was to investigate whether impairments in the ability to execute flexible goal-directed actions may be an underlying feature in ASD contributing to these symptoms. Young adults diagnosed with ASD were recruited along with controls and adults with social anxiety disorder (SAD). Participants were trained to make keyboard actions for food outcomes and then subsequently allowed to consume one outcome till satiety. As expected, this outcome devaluation procedure reduced subsequent responding for actions predicting the devalued outcome, while maintaining responding on the other still valued action, in controls. However, both ASD and SAD participants were unable to demonstrate flexible goal-directed actions, and were insensitive to the change in outcome value on subsequent action control. This behavioral deficit was not due to impairments in appropriate contingency awareness, as all groups rated the devalued food outcome as less pleasant after devaluation. A lack of control over actions may underlie persistent and habitual actions in anxiety-inducing contexts typical in both ASD and SAD, such as avoidance and safety behaviors. Using a translational behavioral paradigm, this study demonstrated that individuals with ASD are unable to use changes in the environment to flexibly update their behavior in the same context. This reduced behavioral control may underlie persistence of intrusive actions and restricted inflexible cognition, representing a specific area for targeted behavioral interventions. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2016, 9: 1285-1293. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26999794 TI - Exploration of shoulder load during hand-rim wheelchair start-up with and without power-assisted propulsion in experienced wheelchair users. AB - BACKGROUND: Frequent start movements occurred during the day, yielding high upper extremity stress. The high incidence and impact of shoulder injury on daily life wheelchair use made it clinically relevant to investigate whether power-assisted propulsion is beneficial during the start. METHODS: Eleven hand-rim wheelchair users performed a start-movement in an instrumented wheelchair on a flat surface. Test order was randomly assigned to propulsion with and without power-assist. For each subject, parameters were averaged over 3 repeated starts. For statistical analysis Wilcoxon Signed Rank test was used. FINDINGS: Intensity of mechanical shoulder loading decreased during power-assisted propulsion for anterior (147.0 (44.8) versus 121.9 (27.4) N; effect size (r)=-.75), posterior (4.8 (14.1) versus 2.7 (11.6) N; r=-.64) and inferior directed forces (82.6 (27.9) versus 68.9 (22.6) N; r=-.78) and abduction (20.2 (14.6) versus 12.9 (7.8) Nm; r=-.88) and extension moments (20.3 (10.7) versus 13.7 (9.1 Nm; r=-.88). Peak resultant force at the rim significantly decreased from 133.5 (38.4) N to 112.2 (25.4) N (r=-.64) and was accompanied by significant decreased shoulder abduction (35.3 (6.7) versus 33.3 (6.8); r=-.67) and significant increased shoulder extension (13.6 (16.3) versus 20.3 (19.1); r=-.78) during power-assisted start-up. INTERPRETATION: Power-assist hand-rim wheelchairs are effective in reducing external shoulder load and partly effective in reducing force generation in extremes of shoulder motion during start-up. The use of power-assist wheels might reduce the risk of developing shoulder overuse injuries. CLINICAL TRIAL REGISTRATION NUMBER: NTR2661. PMID- 26999795 TI - Volatiles from Plants Induced by Multiple Aphid Attacks Promote Conidial Performance of Lecanicillium lecanii. AB - Herbivore-induced plant volatiles (HIPVs) are clues that help predatory insects search for food. The hypothesis that entomopathogenic fungi, which protect plants, benefit from the release of HIPVs was tested. The plant Arabidopsis thaliana was used as the source of HIPVs. The insect herbivore Lipaphis erysimi (Kaltenbach) was used as the inducer, and the fungal pathogen of the aphid Lecanicillium lecanii was exposed to HIPVs to test our hypothesis. When exposed to aphid-induced A. thaliana volatiles, the mortality of aphids pre-treated with a conidial suspension of L. lecanii, the conidial germination and the appressorial formation were significantly increased compared with the control. The decan-3-ol and 4-methylpentyl isothiocyanate that were detected in the headspace seemed to have positive and negative affection, respectively. Moreover, HIPVs generated from groups of eight aphids per plant promoted significantly increased conidial germination and appressorial formation compared with HIPVs from groups of one, two and four aphids per plant. Our results demonstrated that the pathogenicity of the entomopathogenic fungus L. lecanii was enhanced when exposed to HIPVs and that the HIPVs were affected by the number of insect herbivores that induced them. PMID- 26999796 TI - Evaluation of autonomic nervous system function in children with overactive bladder syndrome. AB - PURPOSE: We aimed to evaluate the autonomic nervous system activity in children with overactive bladder (OAB) syndrome. METHODS: Included in the study were 40 children with overactive bladder and 28 healthy controls. Autonomic tests were performed on all participants, including heart rate interval variation (RRIV), heart rate response to valsalva maneuver, and sympathetic skin response (SSR). RESULTS: Mean valsalva rates in the overactive bladder and control groups were 1.53 +/- 0.29 and 1.30 +/- 0.18, respectively, a statistically significant difference (P < 0.001). Also significantly different were deep breathing RRIV values of the study and control groups: 56.65 +/- 14.66 and 47.92 +/- 10.15, respectively (P = 0.008). No statistical differences were found in SSR when OAB patients were compared with controls (P > 0.05). CONCLUSIONS: This study demonstrated a parasympathetic hyperactivity in children with OAB, results suggesting a dysfunction in their autonomic nervous systems. Neurourol. Urodynam. 36:673-676, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26999797 TI - Experimental Cannabinoid 2 Receptor Inhibition in CNS Injury-Induced Immunodeficiency Syndrome. AB - OBJECTIVE: Severe CNS injury, such as stroke, traumatic brain injury, or spinal cord injury, is known to increase susceptibility to infections. The increased susceptibility to infection is due to an impaired immune response and is referred to as CIDS. The CB2 receptor on immune cells presents a potential therapeutic target in CIDS as activation of this receptor has been shown to be involved in immunosuppression. The main purpose of this study was to determine the impact of CB2 receptor inhibition on leukocyte activation within the microcirculation following endotoxin challenge in an experimental stroke model. METHODS: Five experimental groups (male C57BL/6 mice, age: 6-8 weeks) were subjected to the following treatments: control; endotoxemia (LPS 5 mg/kg, i.v.); transient cerebral hypoxia-ischemia (HI) + endotoxemia; HI + endotoxemia + CB2 receptor antagonist (AM630 2.5 mg/kg, i.v.). HI was induced by unilateral carotid artery occlusion, followed by 50 minute exposure to a low oxygen atmosphere (8% O2 ). The CB2 receptor antagonist was given 15 min prior to LPS administration. Intravital microscopy (IVM) was carried out 2h after LPS administration. Brains were extracted and stained with tetrazolium chloride (TTC) to measure infarct volume. RESULTS: Compared to endotoxemic animals without CNS injury, mice subjected to HI displayed reduced leukocyte activation in intestinal submucosal venules indicative of CIDS. Administration of the CB2 receptor antagonist in animals with CIDS challenged with endotoxin restored peripheral leukocyte recruitment without a detrimental impact on infarct size. CONCLUSION: We conclude that the ECS is involved in the impaired immune response following CNS injury. Future studies should further explore the CB2 receptor pathway to develop novel therapies for CIDS. PMID- 26999800 TI - The Challenges of Stroke Prediction Scores. PMID- 26999798 TI - Signal transducer and activator of transcription 5 (STAT5) paralog dose governs T cell effector and regulatory functions. AB - The transcription factor STAT5 is fundamental to the mammalian immune system. However, the relationship between its two paralogs, STAT5A and STAT5B, and the extent to which they are functionally distinct, remain uncertain. Using mouse models of paralog deficiency, we demonstrate that they are not equivalent for CD4(+) 'helper' T cells, the principal orchestrators of adaptive immunity. Instead, we find that STAT5B is dominant for both effector and regulatory (Treg) responses and, therefore, uniquely necessary for immunological tolerance. Comparative analysis of genomic distribution and transcriptomic output confirm that STAT5B has fargreater impact but, surprisingly, the data point towards asymmetric expression (i.e. paralog dose), rather than distinct functional properties, as the key distinguishing feature. Thus, we propose a quantitative model of STAT5 paralog activity whereby relative abundance imposes functional specificity (or dominance) in the face of widespread structural homology. PMID- 26999801 TI - Anti-epileptic drugs and bone loss: Phenytoin reduces pro-collagen I and alters the electrophoretic mobility of osteonectin in cultured bone cells. AB - Phenytoin is an antiepileptic drug used in the management of partial and tonic clonic seizures. In previous studies we have shown that valproate, another antiepileptic drug, reduced the amount of two key bone proteins, pro-collagen I and osteonectin (SPARC, BM-40), in both skin fibroblasts and cultured osteoblast like cells. Here we show that phenytoin also reduces pro-collagen I production in osteoblast-like cells, but does not appear to cause a decrease in osteonectin message or protein production. Instead, a 24h exposure to a clinically relevant concentration of phenytoin resulted in a dose-dependent change in electrophoretic mobility of osteonectin, which was suggestive of a change in post-translational modification status. The perturbation of these important bone proteins could be one of the mechanisms to explain the bone loss that has been reported following long-term treatment with phenytoin. PMID- 26999802 TI - Nerve Hypertrophy in Primary Amyloidosis. PMID- 26999799 TI - A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types. AB - There is a continuing need for driver strains to enable cell-type-specific manipulation in the nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of marker genes by BAC transgenesis or knock in has generated useful transgenic mouse lines. However, since genes are often expressed in many cell types, many of these lines have relatively broad expression patterns. We report an alternative transgenic approach capturing distal enhancers for more focused expression. We identified an enhancer trap probe often producing restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac transposon. We established more than 200 lines and found many lines that label small subsets of neurons in brain substructures, including known and novel cell types. Images and other information about each line are available online (enhancertrap.bio.brandeis.edu). PMID- 26999803 TI - Succinate Accumulation and Ischemia-Reperfusion Injury: Of Mice but Not Men, a Study in Renal Ischemia-Reperfusion. AB - A recent seminal paper implicated ischemia-related succinate accumulation followed by succinate-driven reactive oxygen species formation as a key driver of ischemia-reperfusion injury. Although the data show that the mechanism is universal for all organs tested (kidney, liver, heart, and brain), a remaining question is to what extent these observations in mice translate to humans. We showed in this study that succinate accumulation is not a universal event during ischemia and does not occur during renal graft procurement; in fact, tissue succinate content progressively decreased with increasing graft ischemia time (p < 0.007). Contrasting responses were also found with respect to mitochondrial susceptibility toward ischemia and reperfusion, with rodent mitochondria robustly resistant toward warm ischemia but human and pig mitochondria highly susceptible to warm ischemia (p < 0.05). These observations suggest that succinate-driven reactive oxygen formation does not occur in the context of kidney transplantation. Moreover, absent allantoin release from the reperfused grafts suggests minimal oxidative stress during clinical reperfusion. PMID- 26999804 TI - Comparison of three-dimensional analysis and stereological techniques for quantifying lithium-ion battery electrode microstructures. AB - Lithium-ion battery performance is intrinsically linked to electrode microstructure. Quantitative measurement of key structural parameters of lithium ion battery electrode microstructures will enable optimization as well as motivate systematic numerical studies for the improvement of battery performance. With the rapid development of 3-D imaging techniques, quantitative assessment of 3-D microstructures from 2-D image sections by stereological methods appears outmoded; however, in spite of the proliferation of tomographic imaging techniques, it remains significantly easier to obtain two-dimensional (2-D) data sets. In this study, stereological prediction and three-dimensional (3-D) analysis techniques for quantitative assessment of key geometric parameters for characterizing battery electrode microstructures are examined and compared. Lithium-ion battery electrodes were imaged using synchrotron-based X-ray tomographic microscopy. For each electrode sample investigated, stereological analysis was performed on reconstructed 2-D image sections generated from tomographic imaging, whereas direct 3-D analysis was performed on reconstructed image volumes. The analysis showed that geometric parameter estimation using 2-D image sections is bound to be associated with ambiguity and that volume-based 3-D characterization of nonconvex, irregular and interconnected particles can be used to more accurately quantify spatially-dependent parameters, such as tortuosity and pore-phase connectivity. PMID- 26999805 TI - Maternal Leisure-time Physical Activity and Risk of Preterm Birth: A Systematic Review of the Literature. AB - BACKGROUND: Preterm birth is a leading cause of infant death and the role of maternal physical activity on this risk remains unclear. This systematic review examined low, moderate and vigorous leisure-time physical activity (LTPA) during pregnancy and the outcome of preterm birth. METHODS: Key words related to preterm birth and physical activity were used to search relevant databases (Medline, Cochrane, CINAHL, Sports Discuss and Scopus). Studies were excluded if they did not measure physical activity as an exposure in pregnant women, did not provide information on gestational age at delivery, and were not published in English. All study designs and sample sizes were considered. RESULTS: The search generated 1472 studies. There were 27 studies included in this review of which 23 received high quality reporting scores. Eleven studies reported a lower risk of preterm birth for women who performed LTPA during pregnancy, while 14 studies reported null findings. Only 2 studies detected a significantly higher risk of preterm birth with LTPA during pregnancy. CONCLUSION: This review of literature up to 2014 provides additional evidence to support the assertion that healthy pregnant women can engage in low, moderate, and even some vigorous levels of LTPA without risk for preterm birth. PMID- 26999806 TI - A dynamic and integrated model of gastric HCl secretion: Focus on "Computer modeling of gastric parietal cell: significance of canalicular space, gland lumen, and variable canalicular [K+]". PMID- 26999808 TI - Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. AB - Thiamin is essential for normal metabolism in pancreatic acinar cells (PAC) and is obtained from their microenvironment through specific plasma-membrane transporters, converted to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria through the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). TPP is essential for normal mitochondrial function. We examined the effect of long-term/chronic exposure of PAC in vitro (pancreatic acinar 266-6 cells) and in vivo (wild-type or transgenic mice carrying the SLC25A19 promoter) of the cigarette smoke toxin, 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), on the MTPP uptake process. Our in vitro and in vivo findings demonstrate that NNK negatively affects MTPP uptake and reduced expression of MTPPT protein, MTPPT mRNA, and heterogenous nuclear RNA, as well as SLC25A19 promoter activity. The effect of NNK on Slc25a19 transcription was neither mediated by changes in expression of transcriptional factor NFY-1 (known to drive SLC25A19 transcription), nor due to changes in methylation profile of the Slc25a19 promoter. Rather, it appears to be due to changes in histone modifications that involve significant decreases in histone H3K4-trimethylation and H3K9-acetylation (activation markers). The effect of NNK on MTPPT function is mediated through the nonneuronal alpha7-nicotinic acetylcholine receptor (alpha7-nAChR), as indicated by both in vitro (using the nAChR antagonist mecamylamine) and in vivo (using an alpha7-nAchR(-/-) mouse model) studies. These findings demonstrate that chronic exposure of PAC to NNK negatively impacts PAC MTPP uptake. This effect appears to be exerted at the level of Slc25a19 transcription, involve epigenetic mechanism(s), and is mediated through the alpha7-nAchR. PMID- 26999807 TI - Hydrophobic bile acid apoptosis is regulated by sphingosine-1-phosphate receptor 2 in rat hepatocytes and human hepatocellular carcinoma cells. AB - The hepatotoxic bile acid glycochenodeoxycholate (GCDC) modulates hepatocyte cell death through activation of JNK, Akt, and Erk. The nonhepatotoxic bile acid taurocholate activates Akt and Erk through the sphingosine-1-phosphate receptor 2 (S1PR2). The role of the S1PR2 in GCDC-mediated apoptosis and kinase activation is unknown. Studies were done in rat hepatocytes, HUH7 cells, and HUH7 cells stably transfected with rat Ntcp (HUH7-Ntcp). Cells were treated with GCDC and apoptosis was monitored morphologically by Hoechst staining and biochemically by immunoblotting for the active cleaved fragment of caspase 3. Kinase activation was determined by immunoblotting with phospho-specific antibodies. JTE-013, an inhibitor of S1PR2, significantly attenuated morphological evidence of GCDC induced apoptosis and prevented caspase 3 cleavage in rat hepatocytes and HUH7 Ntcp cells. In hepatocytes, JTE-013 mildly suppressed, augmented, and had no effect on GCDC-induced JNK, Akt, and Erk phosphorylation, respectively. Similar results were seen in HUH7-Ntcp cells except for mild suppression of JNK and Erk phosphorylation. Knockdown of S1PR2 in HUH7-Ntcp augmented Akt, inhibited JNK, and had no effect on Erk phosphorylation. GCDC failed to induce apoptosis or kinase activation in HUH7 cells. In conclusion, SIPR2 inhibition attenuates GCDC induced apoptosis and inhibits and augments GCDC-induced JNK and Akt phosphorylation, respectively. In addition, GCDC must enter hepatocytes to mediate cell death or activate kinases. These results suggest that SIPR2 activation is proapoptotic in GCDC-induced cell death but that this effect is not due to direct ligation of the S1PR2 by the bile acid. PMID- 26999810 TI - Variability in Pathologists' Interpretations of Individual Breast Biopsy Slides: A Population Perspective. AB - BACKGROUND: The effect of physician diagnostic variability on accuracy at a population level depends on the prevalence of diagnoses. OBJECTIVE: To estimate how diagnostic variability affects accuracy from the perspective of a U.S. woman aged 50 to 59 years having a breast biopsy. DESIGN: Applied probability using Bayes' theorem. SETTING: B-Path (Breast Pathology) Study comparing pathologists' interpretations of a single biopsy slide versus a reference consensus interpretation from 3 experts. PARTICIPANTS: 115 practicing pathologists (6900 total interpretations from 240 distinct cases). MEASUREMENTS: A single representative slide from each of the 240 cases was used to estimate the proportion of biopsies with a diagnosis that would be verified if the same slide were interpreted by a reference group of 3 expert pathologists. Probabilities of confirmation (predictive values) were estimated using B-Path Study results and prevalence of biopsy diagnoses for women aged 50 to 59 years in the Breast Cancer Surveillance Consortium. RESULTS: Overall, if 1 representative slide were used per case, 92.3% (95% CI, 91.4% to 93.1%) of breast biopsy diagnoses would be verified by reference consensus diagnoses, with 4.6% (CI, 3.9% to 5.3%) overinterpreted and 3.2% (CI, 2.7% to 3.6%) underinterpreted. Verification of invasive breast cancer and benign without atypia diagnoses is highly probable; estimated predictive values were 97.7% (CI, 96.5% to 98.7%) and 97.1% (CI, 96.7% to 97.4%), respectively. Verification is less probable for atypia (53.6% overinterpreted and 8.6% underinterpreted) and ductal carcinoma in situ (DCIS) (18.5% overinterpreted and 11.8% underinterpreted). LIMITATIONS: Estimates are based on a testing situation with 1 slide used per case and without access to second opinions. Population-adjusted estimates may differ for women from other age groups, unscreened women, or women in different practice settings. CONCLUSION: This analysis, based on interpretation of a single breast biopsy slide per case, predicts a low likelihood that a diagnosis of atypia or DCIS would be verified by a reference consensus diagnosis. This diagnostic grey zone should be considered in clinical management decisions in patients with these diagnoses. PRIMARY FUNDING SOURCE: National Cancer Institute. PMID- 26999811 TI - Circulating tight junction proteins mirror blood-brain barrier integrity in leukaemia central nervous system metastasis. AB - The aim of this study was to evaluate the clinical significance of circulating tight junction (TJ) proteins as biomarkers reflecting of leukaemia central nervous system (CNS) metastasis. TJs [claudin5 (CLDN5), occludin (OCLN) and ZO-1] concentrations were measured in serum and cerebrospinal fluid (CSF) samples obtained from 45 leukaemia patients. Serum ZO-1 was significantly higher (p < 0.05), but CSF ZO-1 levels were not significantly higher in the CNS leukaemia (CNSL) compared to the non-CNSL. The CNSL patients also had a lower CLDN5/ZO1 ratio in both serum and CSF than in non-CNSL patients (p < 0.05). The TJ index was negatively associated with WBCCSF , ALBCSF and BBB values in leukaemia patients. Among all of the parameters studied, CLDN5CSF had the highest specificity in discriminating between CNSL and non-CNSL patients. Therefore, analysing serum and CSF levels of CLDN5, OCLN and the CLDN5/ZO1 ratio is valuable in evaluating the potential of leukaemia CNS metastasis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26999813 TI - The Microphthalmia-Associated Transcription Factor p.E318K Mutation Does Not Play a Major Role in Sporadic Renal Cell Tumors from Caucasian Patients. AB - OBJECTIVE: The transcription factor MITF (microphthalmia-associated transcription factor) is known to induce expression of hypoxia-inducible factor (HIF1-alpha), which is involved in renal carcinogenesis. The MITF p.E318K mutation leads to deficient SUMOylation of MITF, resulting in enhanced activation of its target genes. A case-control study on melanoma patients who coincidentally were affected by renal cell carcinoma (RCC) has revealed an elevated risk for mutation carriers to be affected by one or both of these malignancies, suggesting a possible role for MITF p.E318K in renal carcinogenesis. The same study described an MITF mutation frequency of 1.5% in a small cohort of sporadic RCC, but comprehensive data on sporadic renal cell tumors are missing. We therefore tested a large cohort of sporadic renal tumors for MITF p.E318K mutation status. METHODS: Genomic DNA was extracted from 426 formalin-fixed, paraffin-embedded sporadic renal tumors that had been graded according to the 2004 WHO classification of renal tumors and staged according to the 2002 TNM classification. The tumor cohort was enriched with papillary and chromophobe RCC, and also contained benign oncocytomas. DNA was tested for MITF p.E318K by pyrosequencing. RESULTS: Of 403 analyzable tumors, 402 renal tumors were wild-type ones, and only 1 case showed the MITF p.E318K mutation. This tumor was a clear-cell RCC (pT3b N0 M0 G3 according to the TNM classification 2002). The affected patient was male, 61 years old, and had no known coexisting malignancies. CONCLUSION: The MITF p.E318K mutation does not appear to play a major role in sporadic RCC carcinogenesis, but is possibly restricted to a rare subpopulation of inherited RCC. PMID- 26999812 TI - miR-410 and miR-495 Are Dynamically Regulated in Diverse Cardiomyopathies and Their Inhibition Attenuates Pathological Hypertrophy. AB - Noncoding RNAs have emerged as important modulators in cardiac development and pathological remodeling. Recently, we demonstrated that regulation of the Gtl2 Dio3 noncoding RNA locus is dependent on the MEF2 transcription factor in cardiac muscle, and that two of its encoded miRNAs, miR-410 and miR-495, induce robust cardiomyocyte proliferation. Given the possibility of manipulating the expression of these miRNAs to repair the damaged heart by stimulating cardiomyocyte proliferation, it is important to determine whether the Gtl2-Dio3 noncoding RNAs are regulated in cardiac disease and whether they function downstream of pathological cardiac stress signaling. Therefore, we examined expression of the above miRNAs processed from the Gtl2-Dio3 locus in various cardiomyopathies. These noncoding RNAs were upregulated in all cardiac disease models examined including myocardial infarction (MI) and chronic angiotensin II (Ang II) stimulation, and in the cardiomyopathies associated with muscular dystrophies. Consistent with these observations, we show that the Gtl2-Dio3 proximal promoter is activated by stress stimuli in cardiomyocytes and requires MEF2 for its induction. Furthermore, inhibiting miR-410 or miR-495 in stressed cardiomyocytes attenuated the hypertrophic response. Thus, the Gtl2-Dio3 noncoding RNA locus is a novel marker of cardiac disease and modulating the activity of its encoded miRNAs may mitigate pathological cardiac remodeling in these diseases. PMID- 26999815 TI - Localised Infection of Atlantic Salmon Epithelial Cells by HPR0 Infectious Salmon Anaemia Virus. AB - Infectious salmon anaemia (ISA) is an important, systemic viral disease of farmed Atlantic salmon, Salmo salar L. Endothelial cells are the main target cells for highly virulent HPR-deleted ISA virus (ISAV) types. Here we examine the pathogenesis of non-virulent ISAV HPR0 infections, presenting evidence of an epithelial tropism for this virus type, including actual infection and replication in the epithelial cells. Whereas all HPR0 RT-qPCR positive gills prepared for cryosection tested positive by immunohistochemistry (IHC) and immunofluorescent labelling, only 21% of HPR0 RT-qPCR positive formalin-fixed paraffin-embedded gills were IHC positive, suggesting different methodological sensitivities. Only specific epithelial cell staining was observed and no staining was observed in endothelial cells of positive gills. Furthermore, using an ISAV segment 7 RT-PCR assay, we demonstrated splicing of HPR0, suggesting initial activation of the replication machinery in the epithelial gill cells. Immunological responses were investigated by the expression of interferon-related genes (e.g. Mx and gammaIP) and by ELISA for presence of anti-ISAV antibodies on samples taken sequentially over several months during an episode of transient HPR0 infection. All fish revealed a variable, but increased expression of the immunological markers in comparison to normal healthy fish. Taken together, we conclude that HPR0 causes a localized epithelial infection of Atlantic salmon. PMID- 26999814 TI - Nuclear Localization of the Autism Candidate Gene Neurobeachin and Functional Interaction with the NOTCH1 Intracellular Domain Indicate a Role in Regulating Transcription. AB - BACKGROUND: Neurobeachin (NBEA) is an autism spectrum disorders (ASD) candidate gene. NBEA deficiency affects regulated secretion, receptor trafficking, synaptic architecture and protein kinase A (PKA)-mediated phosphorylation. NBEA is a large multidomain scaffolding protein. From N- to C-terminus, NBEA has a concanavalin A like lectin domain flanked by armadillo repeats (ACA), an A-kinase anchoring protein domain that can bind to PKA, a domain of unknown function (DUF1088) and a BEACH domain, preceded by a pleckstrin homology-like domain and followed by WD40 repeats (PBW). Although most of these domains mediate protein-protein interactions, no interaction screen has yet been performed. METHODS: Yeast two hybrid screens with the ACA and PBW domain modules of NBEA gave a list of interaction partners, which were analyzed for Gene Ontology (GO) enrichment. Neuro-2a cells were used for confocal microscopy and nuclear extraction analysis. NOTCH-mediated transcription was studied with luciferase reporter assays and qRT PCR, combined with NBEA knockdown or overexpression. RESULTS: Both domain modules showed a GO enrichment for the nucleus. PBW almost exclusively interacted with transcription regulators, while ACA interacted with a number of PKA substrates. NBEA was partially localized in the nucleus of Neuro-2a cells, albeit much less than in the cytoplasm. A nuclear localization signal was found in the DUF1088 domain, which was shown to contribute to the nuclear localization of an EGFP-DPBW fusion protein. Yeast two-hybrid identified the Notch1 intracellular domain as a physical interactor of the PBW domain and a role for NBEA as a negative regulator in Notch-mediated transcription was demonstrated. CONCLUSION: Defining novel interaction partners of conserved NBEA domain modules identified a role for NBEA as transcriptional regulator in the nucleus. The physical interaction of NBEA with NOTCH1 is most relevant for ASD pathogenesis because NOTCH signaling is essential for neural development. PMID- 26999816 TI - Defined Essential 8TM Medium and Vitronectin Efficiently Support Scalable Xeno Free Expansion of Human Induced Pluripotent Stem Cells in Stirred Microcarrier Culture Systems. AB - Human induced pluripotent stem (hiPS) cell culture using Essential 8TM xeno-free medium and the defined xeno-free matrix vitronectin was successfully implemented under adherent conditions. This matrix was able to support hiPS cell expansion either in coated plates or on polystyrene-coated microcarriers, while maintaining hiPS cell functionality and pluripotency. Importantly, scale-up of the microcarrier-based system was accomplished using a 50 mL spinner flask, under dynamic conditions. A three-level factorial design experiment was performed to identify optimal conditions in terms of a) initial cell density b) agitation speed, and c) to maximize cell yield in spinner flask cultures. A maximum cell yield of 3.5 is achieved by inoculating 55,000 cells/cm2 of microcarrier surface area and using 44 rpm, which generates a cell density of 1.4x106 cells/mL after 10 days of culture. After dynamic culture, hiPS cells maintained their typical morphology upon re-plating, exhibited pluripotency-associated marker expression as well as tri-lineage differentiation capability, which was verified by inducing their spontaneous differentiation through embryoid body formation, and subsequent downstream differentiation to specific lineages such as neural and cardiac fates was successfully accomplished. In conclusion, a scalable, robust and cost effective xeno-free culture system was successfully developed and implemented for the scale-up production of hiPS cells. PMID- 26999817 TI - Improved survival time trends in Hodgkin's lymphoma. AB - There have been dramatic changes in the staging and treatment of Hodgkin's lymphoma (HL) over the past 30 years. We undertook this study to determine if a stage migration had occurred and also examined if treatment associated with later years has improved survival. Patients with stage I-IV HL between 1983 and 2011 were selected from the Surveillance, Epidemiology, and End Results database. Multivariable analysis (MVA) was performed using Cox proportional hazards modeling. The study cohort included 35,680 patients. The stage breakdown in 1983 according to A and B symptoms was follows: 18%, 21%, 12%, and 5% for stage IA, IIA, IIIA, and IVA disease, respectively, and 6%, 11%, 12%, and 15% for stage IB, IIB, IIIB, and IVB disease. The stage breakdown in 2011 according to A and B symptoms was follows: 9%, 29%, 10%, and 6% for stage IA, IIA, IIIA, and IVA disease, respectively, and 4%, 16%, 12%, and 13% for stage IB, IIB, IIIB, and IVB disease. The median follow-up for the entire cohort is 6.1 years. On MVA, the HR for mortality of patients diagnosed in 2006 was 0.60 (95% Confidence Interval (CI): 0.52-0.70) compared to 1983. For stage I and II patients diagnosed in 2006 the HR was 0.62 (95% CI: 0.44-0.87) and 0.40 (95% CI: 0.30-0.55), respectively, compared to patients diagnosed in 1983. For stage III and IV patients diagnosed in 2006 the HR was 0.72 (95% CI: 0.53-0.98) and 0.74 (95% CI: 0.56-0.99), respectively, compared to patients diagnosed in 1983. This is the first study to demonstrate a significant stage migration in early stage Hodgkin's lymphoma. Furthermore, these results demonstrate an improvement in survival over time for patients with Hodgkin's lymphoma which was particularly notable for those with early stage disease. PMID- 26999818 TI - Evaluation of Trimethoprim/Sulfamethoxazole (SXT), Minocycline, Tigecycline, Moxifloxacin, and Ceftazidime Alone and in Combinations for SXT-Susceptible and SXT-Resistant Stenotrophomonas maltophilia by In Vitro Time-Kill Experiments. AB - BACKGROUND: The optimal therapy for infections caused by Stenotrophomonas maltophilia (S. maltophilia) has not yet been established. The objective of our study was to evaluate the efficacy of trimethoprim/sulfamethoxazole (SXT), minocycline, tigecycline, moxifloxacin, levofloxacin, ticarcillin-clavulanate, polymyxin E, chloramphenicol, and ceftazidime against clinical isolated S. maltophilia strains by susceptibility testing and carried out time-kill experiments in potential antimicrobials. METHODS: The agar dilution method was used to test susceptibility of nine candidate antimicrobials, and time-killing experiments were carried out to evaluate the efficacy of SXT, minocycline, tigecycline, moxifloxacin, levofloxacin, and ceftazidime both alone and in combinations at clinically relevant antimicrobial concentrations. RESULTS: The susceptibility to SXT, minocycline, tigecycline, moxifloxacin, levofloxacin, ticarcillin-clavulanate, chloramphenicol, polymyxin E, and ceftazidime were 93.8%, 95.0%, 83.8%, 80.0%, 76.3%, 76.3%, 37.5%, 22.5%, and 20.0% against 80 clinical consecutively isolated strains, respectively. Minocycline and tigecycline showed consistent active against 22 SXT-resistant strains. However, resistance rates were high in the remaining antimicrobial agents against SXT resistant strains. In time-kill experiments, there were no synergisms in most drug combinations in time-kill experiments. SXT plus moxifloxacin displayed synergism when strains with low moxifloxacin MICs. Moxifloxacin plus Minocycline and moxifloxacin plus tigecycline displayed synergism in few strains. No antagonisms were found in these combinations. Overall, compared with single drug, the drug combinations demonstrated lower bacterial concentrations. Some combinations showed bactericidal activity. CONCLUSIONS: In S. maltophilia infections, susceptibility testing suggests that minocycline and SXT may be considered first-line therapeutic choices while tigecycline, moxifloxacin, levofloxacin, and ticarcillin-clavulanate may serve as second-line choices. Ceftazidime, colistin, and chloramphenicol show poor active against S. maltophilia. However, monotherapy is inadequate in infection management, especially in case of immunocompromised patients. Combination therapy, especially SXT plus moxifloxacin, may benefit than monotherapy in inhibiting or killing S. maltophilia. PMID- 26999819 TI - Corrigendum: Surfactant-Templated Synthesis of Polypyrrole Nanocages as Redox Mediators for Efficient Energy Storage. PMID- 26999820 TI - Tree Size Inequality Reduces Forest Productivity: An Analysis Combining Inventory Data for Ten European Species and a Light Competition Model. AB - Plant structural diversity is usually considered as beneficial for ecosystem functioning. For instance, numerous studies have reported positive species diversity-productivity relationships in plant communities. However, other aspects of structural diversity such as individual size inequality have been far less investigated. In forests, tree size inequality impacts directly tree growth and asymmetric competition, but consequences on forest productivity are still indeterminate. In addition, the effect of tree size inequality on productivity is likely to vary with species shade-tolerance, a key ecological characteristic controlling asymmetric competition and light resource acquisition. Using plot data from the French National Geographic Agency, we studied the response of stand productivity to size inequality for ten forest species differing in shade tolerance. We fitted a basal area stand production model that included abiotic factors, stand density, stand development stage and a tree size inequality index. Then, using a forest dynamics model we explored whether mechanisms of light interception and light use efficiency could explain the tree size inequality effect observed for three of the ten species studied. Size inequality negatively affected basal area increment for seven out of the ten species investigated. However, this effect was not related to the shade tolerance of these species. According to the model simulations, the negative tree size inequality effect could result both from reduced total stand light interception and reduced light use efficiency. Our results demonstrate that negative relationships between size inequality and productivity may be the rule in tree populations. The lack of effect of shade tolerance indicates compensatory mechanisms between effect on light availability and response to light availability. Such a pattern deserves further investigations for mixed forests where complementarity effects between species are involved. When studying the effect of structural diversity on ecosystem productivity, tree size inequality is a major facet that should be taken into account. PMID- 26999821 TI - Registered Report: COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. AB - The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "COT drives resistance to RAF inhibition through MAPK pathway reactivation" by Johannessen and colleagues, published in Nature in 2010 (Johannessen et al., 2010). The key experiments to be replicated are those reported in Figures 3B, 3D E, 3I, and 4E-F. In Figures 3B, D-E, RPMI-7951 and OUMS023 cells were reported to exhibit robust ERK/MEK activity concomitant with reduced growth sensitivity in the presence of the BRAF inhibitor PLX4720. MAP3K8 (COT/TPL2) directly regulated MEK/ERK phosphorylation, as the treatment of RPMI-7951 cells with a MAP3K8 kinase inhibitor resulted in a dose-dependent suppression of MEK/ERK activity (Figure 3I). In contrast, MAP3K8-deficient A375 cells remained sensitive to BRAF inhibition, exhibiting reduced growth and MEK/ERK activity during inhibitor treatment. To determine if RAF and MEK inhibitors together can overcome single agent resistance, MAP3K8-expressing A375 cells treated with PLX4720 along with MEK inhibitors significantly inhibited both cell viability and ERK activation compared to treatment with PLX4720 alone, as reported in Figures 4E-F. The Reproducibility Project: Cancer Biology is collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife. PMID- 26999822 TI - The hierarchical organization of the lateral prefrontal cortex. AB - Higher-level cognition depends on the lateral prefrontal cortex (LPFC), but its functional organization has remained elusive. An influential proposal is that the LPFC is organized hierarchically whereby progressively rostral areas of the LPFC process/represent increasingly abstract information facilitating efficient and flexible cognition. However, support for this theory has been limited. Here, human fMRI data revealed rostral/caudal gradients of abstraction in the LPFC. Dynamic causal modeling revealed asymmetrical LPFC interactions indicative of hierarchical processing. Contrary to dominant assumptions, the relative strength of efferent versus afferent connections positioned mid LPFC as the apex of the hierarchy. Furthermore, cognitive demands induced connectivity modulations towards mid LPFC consistent with a role in integrating information for control operations. Moreover, the strengths of these dynamics were related to trait measured higher-level cognitive ability. Collectively, these results suggest that the LPFC is hierarchically organized with the mid LPFC positioned to synthesize abstract and concrete information to control behavior. PMID- 26999823 TI - Feasibility and Effectiveness of a Web-Based Physical Activity Intervention for Working Mothers. AB - BACKGROUND: The purpose of this study was to examine the feasibility and effectiveness of a web-based intervention to promote physical activity and self worth among working mothers. METHODS: Participants (N = 69) were randomly assigned to receive a standard web-based intervention or an enhanced intervention that included group dynamics strategies to promote engagement. The 8-week intervention was guided by self-determination theory. Each week, participants were instructed to complete 3 tasks: listen to a podcast related to well-being, complete a workbook assignment, and communicate with other participants on a discussion board. Participants in the enhanced condition received an additional weekly task to enhance group cohesion. Data were collected at baseline, week 8, and week 16. RESULTS: Physical activity (P < .001, eta2 = 0.35) and self-worth (P < .001, eta2 = 0.39) increased significantly in both groups following the intervention, and introjected (P < .001, eta2 = 0.30) and external motivation (P = .04, eta2 = 0.10) decreased. Website use declined across the 8-week intervention in both groups (P < .001, eta2 = 0.48); however, discussion board use was higher in the enhanced condition (P = .04, eta2 = 0.21). CONCLUSIONS: These findings suggest web-based interventions can improve physical activity and self-worth among working mothers. Group dynamics strategies only minimally enhanced user engagement, and future studies are needed to optimize web-based intervention designs. PMID- 26999825 TI - Physical Activity Trends of Finnish Adolescents With Long-Term Illnesses or Disabilities From 2002-2014. AB - BACKGROUND: Adolescents' physical activity level is a major source of concern. For adolescents with long-term illnesses or disabilities (LTID), being physically active can prevent secondary conditions. This is one of the first studies reporting trends in physical activity of adolescents with LTID in relation to gender, age, and sports club membership. METHODS: Data were collected from the Health Behavior in School-aged Children study in Finland during 2002, 2006, 2010, and 2014. In 13- and 15-year-olds (N = 2206), 17.1% reported having LTID. Daily physical activity recall was the dependent variable. Binary logistic regression analysis was conducted separately for sports club members (n = 936) and nonmembers (n = 1270). RESULTS: The proportion of physically active adolescents with LTID in 2014 was higher than in 2002 for girls (15.6% vs 8.7%) and boys (26.6% vs 13.0%). Girl sports club members were 2 times more likely to be physically active in 2014 than in 2002. The largest trend between 2014 and 2002 was among boy nonmembers (odds ratio: 4.62, 95% confidence interval, 2.02-10.58). CONCLUSIONS: More adolescents with LTID took part in daily moderate-to-vigorous physical activity in 2014 than in 2002; however, physical activity levels still remain low. Sports club membership was similar to that of the general population. PMID- 26999826 TI - NIH Analysis Shows Americans Are in Pain. PMID- 26999827 TI - NIH Study Shows No Benefit of Omega-3 or Other Nutritional Supplements for Cognitive Decline. PMID- 26999824 TI - Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import. AB - Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated beta-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. PMID- 26999828 TI - Teens Using E-Cigarettes May Be More Likely to Start Smoking Tobacco. PMID- 26999829 TI - Hypothermia and Older Adults. PMID- 26999830 TI - Patient Engagement Advisory Committee. Final rule. AB - The Food and Drug Administration (FDA) is amending the standing advisory committees' regulations to add the Patient Engagement Advisory Committee. PMID- 26999831 TI - Payment for Physician and Other Health Care Professional Services Purchased by Indian Health Programs and Medical Charges Associated With Non-Hospital-Based Care. Final rule with comment period. AB - The Secretary of the Department of Health and Human Services (HHS) hereby issues this final rule with comment period to implement a methodology and payment rates for the Indian Health Service (IHS) Purchased/Referred Care (PRC), formerly known as the Contract Health Services (CHS), to apply Medicare payment methodologies to all physician and other health care professional services and non-hospital-based services. Specifically, it will allow the health programs operated by IHS, Tribes, Tribal organizations, and urban Indian organizations (collectively, I/T/U programs) to negotiate or pay non-I/T/U providers based on the applicable Medicare fee schedule, prospective payment system, Medicare Rate, or in the event of a Medicare waiver, the payment amount will be calculated in accordance with such waiver; the amount negotiated by a repricing agent, if applicable; or the provider or supplier's most favored customer (MFC) rate. This final rule will establish payment rates that are consistent across Federal health care programs, align payment with inpatient services, and enable the I/T/U to expand beneficiary access to medical care. A comment period is included, in part, to address Tribal stakeholder concerns about the opportunity for meaningful consultation on the rule's impact on Tribal health programs. PMID- 26999832 TI - [The study of external factors affecting auditory ability of infants and toddlers after cochlear implantation]. AB - OBJECTIVE: To analyze external factors affecting auditory ability of infants and toddlers after cochlear implantation in the first year of switch-on. METHOD: Seventy-five infants and toddlers after cochlear implantation were selected as subjects, using LittlEARS Auditory Questionnaire to assess and analyze the correlations with auditory ability and external factors (including gender, cochlear implanted age, pre-implant hearing aid fitting, caregivers' education background, household income and rehabilitation modes) in different stages (before switch-on, and 3 months, 6 months, 9 months, 12 months after switch-on). RESULT: The mean scores of LittlEARS were significantly different in cochlear implanted age group, pre-implant hearing aid fitting group and rehabilitation modes group (P < 0.05), and there was no significant difference in other groups such as external factor gender, caregivers' education background and household income (P > 0.05). The correlations with the mean scores of LittlEARS and cochlear implantation age or pre-implant hearing aid fitting were significant at 3 months or 6 months after switch-on(/r/ >= 0. 3, P < 0.01). However, the correlation with the mean scores of LittlEARS and rehabilitation modes was significant at 12 months after switch-on(/r/ > >= 0.3, P < 0.01). CONCLUSION: Cochlear implanted age and pre-implant hearing aid fitting were the important factors affecting auditory ability of infants and toddlers after cochlear implantation in the first year of switch-on. The effect of rehabilitation modes on auditory ability of infants and toddlers after cochlear implantation was slow. PMID- 26999833 TI - [Analysis of the deafness gene screening results from newborns in Shijiazhuang]. AB - OBJECTIVE: To build information repository of the carrying rate of neonatal deafness gene in Shijiazhuang. METHOD: Blood samples were collected from the heel in 3-days neonates. Mutations of the deafness related genes were detected by the method of fluorescent PCR. Neonates received the detection of 6 mutation sites from 3 genes, including GJB2 (235delC, 299-300delAT), SLC26A4 (IVS7-2A> G, 2168A> G), mitochondrial DNA12S rRNA(1494C>T,1555A>G). RESULT: There were 384 neonates who carried mutations among 421 subjects and the carrying rate was 4.08%, 158 (1.68%) newborns carried heterozygous mutations and 1 (0.01%) case carried homogeneous mutation of GJB2 (235 delC), 55 (0.58%) neonates carried heterozygous mutations of GJB2 (299-300delAT); 133 (1.41%) neonates carried heterozygous mutations and 1 (0.01%) homogeneous of SLC26A4(IVS7-2A>G),19 (0.20%) newborns carried heterozygous mutations of SLC26A4 (2168A>G). The numbers of neonates who carried homogeneous and heterogeneous mutation of mitochondrial 12S rRNA gene were 14 and 3 with carring rates of 0.15% and 0.03%. Two newborns were found to carry more than one mutation. One carried 235delC, IVS7-2A>G and 1555A>G and another carried 235delC and IVS7-2A>G. CONCLUSION: The main mutational patterns were 235delC from GJB2 gene and IVS7-2A>G from SLC26A4 gene in Shijiazhuang newborns. The carrying rate information repository of neonatal deafness gene has been built preliminarily. PMID- 26999834 TI - [The application of autologous conchal cartilage in ossicular chain reconstruction]. AB - OBJECTIVE: To evaluate the efficiency of autologous conchal cartlage in ossicular chain reconstruction in patients with chronic suppurative otitis media. METHOD: Seventy-three cases of chronic suppurative otitis media (COM) with or without cholesteatoma who had undergone mastoidectomy with tympanoplasty and ossicular chain reconstruction(OCR) using autologous conchal cartilage as prosthesis were studied retrospectively. Sixty-six cases of COM who had undergone mastoidectomy with tympanoplasty and without OCR were studied as control. The examination of pure tone hearing level of air conduction(AC) and bone conduction(BC) was done before operation, 2 months and 6 months after operation respectively. The pure tone average (PTA) of 0.5, 1.0, 2.0 kHz was observed. RESULT: The average air conduction gain was more than 15dB or the PTA (AC) was less than 25 dB 2 months after operation in 35 out of 73 cases who had undergone OCR. Nevertheless, the data became 56 out of 73 cases 6 months after operation. In the control group, The average air conduction gain was more than 15dB or the PTA(AC) was less than 25 dB 2 months after operation in 10 out of 66 cases who had not undergone OCR. The data became 14 out of 66 cases 6 months after operation. In OCR group, air bone gap(ABG) was less than 20 dB in 39 cases 2 months after operation and in 57 cases 6 months after operation. In the control group without OCR, ABG was less than 20 dB only in 11 cases 2 months after operation and in 16 cases 6 months after operation. By statistically analysis, there was significant difference of postoperative hearing improvement between the two groups. CONCLUSION: The autologous conchal cartilage can be used as the material of prosthesis for ossicular chain reconstruction in the operation of chronic otitis media. It has many advantages, such as easily--obtained, good histocompatibility, easy to shape and so on. PMID- 26999835 TI - [Measurements of semicircular canal space direction with MRI]. AB - OBJECTIVE: Measure the space direction of semicircular canals to provide the anatomical basis for the diagnosis and treatment of BPPV. METHOD: We calculated angles among semicircular canals of 24 patients using MRI scaning with 3D-CISS sequence. RESULT: The angle between the left and right posterior semicircular canals was 106.61 degress +/- 8.58 degrees, so the angle among the posterior semicircular canals and sagittal head plane was 53.31 degrees +/- 4.29 degrees. Pairs of contralateral synergistic canal planes were not parallel, forming 171.67 degrees +/- 4.36 degrees between the left and right horizontal semicircular canal planes, 154.37 degrees +/- 10.87 degrees between the left posterior and right anterior semicircular canal planes and 156.84 degrees +/- 9.34 degrees between the right posterior and left anterior semicircular canal planes. CONCLUSION: Our measurement of the angles among semicircular canals coincided with those of previous reports. The angles between contralateral synergistic canal planes were close to parallel, but the angle between the posterior semicircular canals and sagittal head plane was great than 45 degrees that traditionally thought to be. PMID- 26999836 TI - [The anatomic study of tragal cartilage and its clinical application in ear surgery]. AB - OBJECTIVE: Dissecting adult cadaver's tragal cartilage and researching its clinical application in ear surgery. METHOD: Dissect the bilateral tragal cartilage of 22 adult cadavers immersed in formalin (both of male and female are 11). Measure and compute the average value of the length, width, thickness and area. Summarize autologous tragal cartilage's clinical application in ear surgery. RESULT: The statistic values of male tragal cartilage were: length (22.55 +/- 0.89) mm, width (19.00 +/- 1.09) mm, thickness (1.04 +/- 0.09) mm, and area (315.70 +/- 32.57) mm2. The statistic values of female respectively were (19.36 +/- 0.86) mm, (15.73 +/- 0.69) mm, (0.93 +/- 0.06) mm, and (229.64 +/- 13.97) mm2. Tragal cartilages were utilized in 419 middle ear surgeries in my department, including tympanoplasty(type I 189 cases, type II and III 116 cases), atticotomy (65 cases), and the repair of the lateral skull base (3 cases). The postoperative effect was satisfactory. CONCLUSION: Tragal cartilage is in the operation region, which is convenient to be harvested and shaped. Hence, the donor can satisfy the requirement of general ear surgery and it is suitable for widely application in ear surgery. PMID- 26999837 TI - [Efficacy of intratympanic steroid injection as supplementary or initial treatment for sudden sensorineural hearing loss]. AB - OBJECTIVE: To observe the efficacy of intratympanic steroid injection as supplementary or initial treatment for sudden sensorineural hearing loss (SSNHL). METHOD: A total of 68 patients diagnosed with SSNHL were randomized into group A (45 cases including systemic steroid for 33 cases and systemic steroid + intratympanic steroid as supplementary treatment for 12 cases) and group B (23 cases, initial intratympanic steroid). Then observe the therapeutic effect in two groups. RESULT: The total effective rate was 55.6% in group A and 56.5% in group B. No statistical difference was detected between these two groups (P > 0.05). There was statistical difference after therapy of intratympanic steroid as supplementary treatment for 12 patients due to poor hearing improvement after systemic steroid in group A (P < 0.05). CONCLUSION: Both systemic and intratympanic steroid injection for SSNHL are effective. The efficiency of intratympanic steroid injection as supplementary or initial treatment for SSNHL is similar to that of systemic steroid. The intratympanic steroid injection for SSNHL as initial protocol or as supplementary treatment when poor hearing improvement after systemic steroid is recommended. PMID- 26999838 TI - [Value of e-Flow combined with TI-RADS in qualitative diagnosis of thyroid nodules]. AB - OBJECTIVE: To investigate the value of combination of thyroid imaging reporting and data system (TI-RADS) and enhanced flow (e-Flow) in the qualitative diagnosis of thyroid nodules; and to compare the diagnostic efficiency between e-Flow and color doppler flow imaging (CDFI. METHOD: The study chose 133 patients with 179 nodules (127 benign, 52 malignant nodules) who had per-operative ultrasound examination of their thyroid using grey-scale ultrasound, CDFI, e-Flow, and their noudles were graded by TI-RADS. Then the ultrasound diagnostic value were compared with their surgical pathology results by TI-RADS; TI-RADS and CDFI; TI RADS and e-Flow, and diagnostic efficiency between e-Flow and CDFI were compared. RESULT: The results revealed that combination of TI-RADS and e-Flow had a higher sensitivity (94.23%, P < 0.05). There was no statistically significant difference between TI-RADS and the combination of TI-RADS and CDFI. Likewise, there was no significant difference between the combination of TI-RADS and e-Flow and the combination of TI-RADS and CDFI. The e-Flow showed a higher sensitivity, specificity and accuracy compare to the CDFI. CONCLUSION: Combining e-Flow and TI RADS could improve the sensitivity in qualitative diagnosis of thyroid nodules. Also, e-Flow has a better diagnostic efficiency of thyroid nodules. PMID- 26999839 TI - [Observation of the efficacy of allergen blocking nasal spray in patients with rhinitis sicca]. AB - OBJECTIVE: To observe the efficacy of allergen blocking nasal spray (ABNS) , combined with seawater spray (SS) and myrtol standardized capsules (MSS), in patients with rhinitis sicca. METHOD: Patients diagnosed as rhinitis sicca were randomly divided into 2 groups: ABNS+SS group and SS group. In ABNS+SS group, patients used ABNS and SS four times per day and MSS twice per day. In SS group, patients used the same medicine except ABNS. Both group were observed for 14 days. The visual analog scale (VAS) of dryness, the endoscopy evaluation score (EES) and the tolerability of the spray were compared between the 2 groups. RESULT: There were 30 patients included in each group. The VAS and EES were improved in both groups after 2 weeks' treatment. The improvement of VAS and EES in ABNS+SS group was significantly superior to SS group (VAS: P < 0.01, EES: P < 0.05). There were only 2 patients complaint of slight discomfort when using ABNS, which did not disturb the treatment. CONCLUSION: There is good efficacy of allergen blocking nasal spray (ABNS), combined with seawater spray (SS) and myrtol standardized capsules (MSS), in patients with rhinitis sicca. PMID- 26999840 TI - [The expression and clinical significance of Bax and PHF20 in laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To investigate the expression of Bax and PHF20 in laryngeal squamous cell carcinoma (LSCC)and to discuss their relevance and the roles in carcinogenesis and development in LSCC. METHOD: The expressions of Bax and PHF20 in the LSCC tissues and normal mucosa tissues adjacent to carcinoma were detected by SP immunohistochemistry assay. The relationship between the expressions of Bax and PHF20 and the clinicopathological characteristics including clinical stage, pathological type, histological grade and lymph node metastasis in LSCC were analyzed according to the clinical data. RESULT: (1) The expressions of Bax and PHF20 were both significantly lower in the LSCC tissue than that in the normal laryngeal tissue (P < 0.01). (2) In clinical stage grouping, there were no statistical differences of the quantity and positive rate of Bax and PHF20 expressions among supraglottic, glottic and subglottic LSCC (P > 0.05). In histological differentiation grouping, the quantity and positive rate of Bax and PHF20 expressions decreased significantly in poorly differentiated LSCC compared with the well and moderately differentiated LSCCs (P < 0.01, P < 0.05, respectively). In T stage grouping, the quantity and positive rate of Bax and PHF20 expressions were both significantly higher in T1 + T2 compared with T3 +T4 (both P < 0.01). In addition, the quantity and positive rate of Bax and PHF20 expressions were both significantly higher in LSCC with lymph node metastasis compared to that without lymph node metastasis (both P < 0.01). CONCLUSION: The lack of Bax and PHF20 might contribute to the carcinogenesis and development in LSCC. The positive expression of Bax and PHF20 maybe relative to T term degree, differentiation degree and lymphamatic metastasis of LSCC. PMID- 26999841 TI - [Analysis of clinical factors for the efficacy of TPF in treating hypopharyngeal carcinoma]. AB - OBJECTIVE: To summarize the clinical effect of TPF regimen in the treatment of hypopharyngeal carcinoma and explore various clinical factors affecting treatment efficacy. METHOD: The clinical data of 20 cases with hypopharyngeal carcinoma, who received TPF treatment, were analyzed retrospectively. After two courses of chemotherapy, based on radiographic outcomes, next treatment plan was developed. To sum up the clinical information, including the clinical type, patterns of tumor growth, pathologic type, tumor stage, lymph node metastasis, age and so on. To analyze possible influencing factors affecting curative effect. RESULT: (1) After 20 cases with hypopharyngeal carcinoma received two courses of TPF treatment, the effect was evaluated. Objective response rate was 65%. (2) In patients with hypopharyngeal carcinoma, the efficacy of TPF therapy was significantly related to the clinical type, patterns of tumor growth and pathologic type; there was no statistical significance in tumor stage, lymph node metastasis and age. CONCLUSION: According to the clinical type, patterns of tumor growth and pathologic type of hypopharyngeal carcinoma, resistance to chemotherapy in hypopharyngeal carcinoma can be assessed, which provides important basis for designing individualized treatment plan. PMID- 26999842 TI - [Application of CO2 laser and self-made laryngeal dilator in the treatment of the laryngeal stenosis]. AB - OBJECTIVE: To study the treatment effect of CO2 laser and self-made laryngeal dilator on the laryngeal stenosis. METHOD: Twenty-five patients with laryngeal stenosis were treated with CO2 laser and self-made laryngeal dilator. The laryngeal cavity scar was resected as much as possible by using CO2 laser and the laryngeal cavity was exposed by placing laryngeal dilator under general anesthesia. RESULT: The 24 cases of all were successfully decanulated 1 to 12 months after operation and could breathe freely. One case had second operation and was successfully decanulated 9 months after operation. The follow-up for 1 to 2 years showed all cases speaking well and 3 cases recurrence. CONCLUSION: The method for treating laryngeal stenosis using CO2 laser and self-mande laryngeal dilator is effective, fewer complication, less invasive, and faster recovery. The laryngeal dilator is made simply and conveniently. PMID- 26999843 TI - [Analysis of bleeding cause after uvulopalatopharyngoplasty with endotherm knife]. AB - OBJECTIVE: To summary and analyze the bleeding causes after uvulopalatopharyngoplasty(UPPP) with endotherm knife, and preventive measures will be given to effectively reduce postoperation hemorrhage. METHOD: Two hundred and twenty-six cases of obstructive sleep apnea hypopnea syndrome (OSAHS) adult patients, were carryed out UPPP under general anesthesia with endotherm knife to observe postoperation hemorrhage. RESULT: Eight cases out of 226 patients or 3.5% occurred postoperation hemorrhage, 2 cases after 1 or 2 days, 6 cases after 6 or 12 days. The postoperation hemorrhage stopped by local compression hemostasis or bi-polar coagulation hemostasis, and no more bleeding occurred. CONCLUSION: The minimal trauma, quick operation and less-bleeding will be caused by UPPP with endotherm knife. Few patients 3.5% had a small amount of bleeding after operation, but no serious bleeding occured. Hemorrhage often happened during pseud mucosa falling off period. The bleeding was related with using skill of endotherm knife during operation, postoperation pse-ud mucosa falling off, local inflammation, improper eating and emotional stress of patients. PMID- 26999844 TI - [Associations of JAK1 gene polymorphisms with allergic rhinitis in Chinese Han populations]. AB - OBJECTIVE: The aim of this study was to investigate the association of JAK1 polymorphisms with allergic rhinitis in China Han population. METHOD: A total of 450 patients with AR and 615 healthy subjects as control were genotyped for the presence of three single nucleotide polymorphisms using polymerase chain reaction restriction fragment length polymorphism (PGR-RFLP) analysis of DNA extracted from blood samples. RESULT: All control subjects were in Hardy-Weinberg equilibrium, but high frequencies of JAK1 the homozygous rs310241 CC genotype were observed in AR patients compared to controls (P < 0.05). The results also revealed that there was no association between the rest of two investigated SNPs and AR. CONCLUSION: Our results suggested that JAK1 gene rs310241 CC genotype was associated with patients with AR. PMID- 26999845 TI - [The pulmonary injury in rats caused by chronic intermittent hypoxia and the intervention effect of Edaravone]. AB - OBJECTIVE: To investigate the mechanism of the pulmonary injury in rats caused by chronic intermittent hypoxia (CIH) and to investigate the intervention effect of Edaravone. METHOD: Ninety-six male Wistar rats were divided into four groups randomly: the control group (NC), chronic intermittent hypoxia group (CIH), chronic intermittent hypoxia normal saline matched group (NS), chronic intermittent hypoxia edaravone treatment group (NE). The four groups were also divided into 1, 2, 3, 4 W time subgroups, and each time subgroup had 6 rats. After the experiment, sections of pulmonary were stained with hematoxylin-eosin (HE) and the level of SOD, MDA, PO2 and Ang II mRNA in rat homogenate pulmonary were measured. RESULT: Pulmonary histology revealed that the CIH group showed high levels of interstitial edema, alveolar atelectasis, inflammatory cell infiltration of alveolar epithelial cell, pulmonary injury were serious in 1, 2, 3, 4 W. But the pulmonary histology of the UC group and the NS group was normal. Compared with the NS group, pulmonary injury of NE group 1, 2, 3, 4 W, significantly decreased. Compared with the NC group, the levels of PO2 in the CIH group were decreased; while the compared with the NS group, the levels of PO2 in the NE group were increased. Compared with the UC group and NS group, the levels of Ang II mRNA in each time point in CIH group were increased gradually (P < 0.05), the content of MDA were increased in 1, 2, 3, 4 W (P < 0.05), they had reached the peak all at 4 W; while the SOD in each time point in CIH group were decreased gradually (P < 0.05) compared with that in UC group and NS group; The Ang II mRNA levels of CIH in pulmonary showed positive correlation with MDA [r = 0.782,P < 0.01]; while the Ang II mRNA levels of CIH in pulmonary showed negative correlation with SOD [r = - 0.904, P < 0.01]. CONCLUSION: CIH can cause pulmonary injury through oxidative stress and activating Ang II, and Edaravone could prevent pulmonary injury induced by CIH through scavenging oxygen free radicals. PMID- 26999847 TI - [The changes and significance of IL-6 levels in patients with OSAHS associated Type 2 diabetes Mellites]. AB - OBJECTIVE: To explore the changes of serum interleukin-6 (IL-6) level in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and OSAHS associated type 2 diabetes mellitus (T2DM) and their significance. METHOD: All observed subjects were divided into 3 groups: 20 cases of normal subjects, 35 cases of simple OSAHS patients, 48 cases of OSAHS associated T2DM patients, IL-6 concentrations of serum were measured by the enzyme-linked immunosorbent. RESULT: IL-6 level was higher in the group of OSAHS with T2DM than the group of OSAHS and the healthy control group (P < 0.05); IL-6 level was higher in the simple OSAHS group than the healthy controls. CONCLUSION: IL-6 and other inflammatory factors may involved pathological physiological process in OSAHS patients sugar metabolic abnormalities; and is associated with the development of OSAHS associated with type 2 diabetes. PMID- 26999846 TI - [The evaluation of 128 slice spiral CT for soft palate, hard palate and mandible in patients with obstructive sleep apnea hypopnea syndrom]. AB - OBJECTIVE: To discuss the soft palate, hard palate and mandibule for the pathogenesis and clinical treatment of patients who have obstructive sleep apnea hypopnea syndrome. METHOD: There were 52 patients with OSAHS diagnosed by the PSG and 32 cases of normal healthy volunteers in our hospital. All objects were given 128 slice spiral CT scan of the upper airway. We measured the related indexes of the soft palate, hard palate and mandible, then analysed statistical differences between them and did Pearson correlation analysis with apnea hypoventilation index (AHI), average blood oxygen saturation (MSaO2) in PSG. RESULT: Compared with the control group, the soft palate length [(37.93 +/- 5.20)mm VS (33.52 +/- 4.25)mm] and the distance between mandible with cervical vertebra [(75.00 +/- 7.10)mm VS (69.93 +/- 5.58)mm] increased significantly, but the distance of trailing edge of hard palate to inferior margin of slope significantly reduced [(42.57 +/- 4.52)mm VS (45.80 +/- 2.94)mm, P < 0.01] in patients with OSAHS. Each measurement associated with AHI and MSaO2 had no significant correlation (P > 0.05). CONCLUSION: The soft palate, hard palate and mandibular are some of the important risk factors of OSAHS, and they also have reference value for the choice of clinical treatment operation. Preoperative CT examination can offer help in the treatment of OSAHS. PMID- 26999848 TI - [To repair defects of facial skin and tissue with the axial flap]. AB - OBJECTIVE: To explore the clinical repair value of facial skin and tissue defect caused by tumour, trauma and infection with the axial flap. METHOD: The clinical data of 38 patients with facial skin and tissue defect were analyzed retrospectively. All of them were repaired by the axial flap. RESULT: The axial flap was alive in all patients, and all incision healed in the first stage. All patients had a satisfied result after the second stage of flap surgery. CONCLUSION: The method of the axial flap in face can be clinically applied in the facial skin and tissue defects caused by tumour, trauma injury and infection. Because the axial flap cotained named blood vessel, the survival rate of it is high. PMID- 26999849 TI - [The clinical observation of the repair of pharyngeal mucosa and neck skin defects with acellular dermal matrix]. AB - OBJECTIVE: To evaluate the clinical effect of acellular dermal matrix (ADM) on the repair of different tissue defects in pharyngeal and laryngeal cancer. METHOD: Twenty-three cases of pharyngeal and laryngeal cancer were analyzed retrospectively, including 16 patients with pharyngeal cancer, and 7 patients with laryngeal cancer. After surgery, the patients appeared two types of tissue defects respectively: hypopharynx tissue defect and neck skin tissue defect. These defects were repaired with ADM, and the clinical effects were observed. RESULT: Sixteen cases of hypopharynx tissue defect and 7 cases of neck skin tissue defect were repaired with ADM. One case in hypopharynx tissue defect group and 2 cases in neck skin tissue defect group undergone pharyngeal fistula postoperatively. CONCLUSION: The repair of tissue defects in pharyngeal and laryngeal cancer with ADM had some advantages, such as good histocompatibility, low immune rejection, wide material sources and simple method. There were some differences in clinical effects between hypopharynx cavity defect and neck skin tissue defects, so the emphasis of the need to pay attention to is different in the clinical. PMID- 26999851 TI - [Clinical analysis of imflammatory myofibroblastic tumor of the nasal cavity and paranasal sinus]. AB - OBJECTIVE: To investigate the clinical features, therapeutic methods and therapeutic efficacy of imflammatory myofibroblastic tumor(IMT)of the nasal cavity and paranasal sinuses. METHOD: Clinical data of 14 cases diagnosed as IMT by pathology were retrospectively analyzed. There were 8 males and 6 females,age ranging from 18 to 77 years. 12 cases of them were treated by surgery while 2 cases received postoperative radiotherapy. RESULT: All cases were operated. All the patients were followed up for a period of 1 to 7 years after operation and two cases were proved low grade IMT pathologically. Eight cases survived with no recurrence until the last follow-up and 6 cases relapsed, of which 4 cases died and 2 were alive with tumor. CONCLUSION: IMT of the nasal cavity and paranasal sinuses is very rare. The diagonosis of IMT is based on pathology and immunohistochemistry. Proper diagnosis is essential to avoid mutilating and disfiguring surgical procedures. Radical excision is still the first choice of treatment for IMT of the nasal cavity and paranasal sinuses. Chemotherapy and radiotherapy may not be helpful to prevent recurrence after operation. Due to high recurrence rate, long-term follow up is necessary after operation. PMID- 26999850 TI - [The clinical analysis of thyriod carcinoma showing thymus-like differentiation]. AB - OBJECTIVE: To investigate the clinical diagnosis, treatment and prognosis of carcinoma showing thymus-like differentiation (CASTLE) of thyroid, and to improve the understanding of CASTLE. METHOD: In 6 patients with CASTLE, we performed region VI lymph node dissection, the lesion resection of thyroid lobe and isthmus. After the operation, except one case of 68 years old patient, the rest patients were treated with radiotherapy 60 Gy in anterior cervical region after third week of operation and 5 courses of chemotherapy with cisplatin, each interval of 2 weeks. Insist on the oral Euthyrox. RESULT: All patients were alive without recurrence and metastasis. CONCLUSION: The diagnosis of CASTLE depends on the histology and immunohistochemistry. Operation was the main treatment. CASTLE is a rare type of thyroid carcinoma with slow progress and good prognosis. PMID- 26999852 TI - [Primary small cell carcinoma of the larynx: a case report of misdiagnosis]. PMID- 26999853 TI - [Treatment of ear keloids by striping combined with asiaticoside ointment and triamcinolone acetonide]. PMID- 26999854 TI - [Fish bone in retropharyngeal treatment with transoral laser CO2 microsurgery: a case report]. AB - Fish bones are the most common pharyngeal foreign bodies encountered in the ENT emergency. Many fish bones may be buried in the surrounding soft tissue of the pharynx and larynx. Any delayed treatment for these foreign bodies may cause catastrophic complications. We present a case of 51-year-old woman who had an ingested fish bone migrating to the retropharyngeal space. We used spiral Computed tomography scanning (CT, taken at intervals of 2mm) with dimensional reconstruction for the accurate location diagnosis and surgical planning. We treated successfully before any complication by transoral Laser CO2 microsurgery. PMID- 26999855 TI - [Advances in diagnosis and treatment of Meniere's disease]. AB - Meniere's disease (MD), a kind of common disease of otology, is based on the endolymphatic hydrops. The clinical features of MD are intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus and ear fullness. With the in-depth exploration of the disease, the diagnosis and treatment of MD has made a series of research results. In this paper, the related literature and research reports in recent years were reviewed. PMID- 26999856 TI - [Advances in minimally invasive cochlear implantation]. AB - Cochlear implantation has gradually been accepted as an effective treatment for many patients with severe to pround sensorineural hearing loss. The traditional cochlear implantation does not exist up to expectations in some respects. With the soft surgery technique brought forward, the idea of minimally invasive cochlear implantation is deely rooted among the people. Now many institutions are carring out a series of clinical researches and practices to improve the results of cochlear implantation surgery and reduce the complications around the world. It includes minimally invasive approach, cochleostomy and electrode insertion techniques, especially the latter two affect the preservation of residual hearing. This article is a review of the advances in minimally invasive cochlear implantation from the above three aspects. PMID- 26999857 TI - [The Voice Foundation 44th Annual Symposium & 12th International Association of Phonosurgery Conference Summary Report]. PMID- 26999858 TI - [THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS]. AB - The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension. PMID- 26999859 TI - [THE DETECTION OF CONTENT OF DIAGNOSTICALLY SIGNIFICANT FATTY ACIDS AND INDIVIDUAL TRIGLYCERIDES IN BIOLOGICAL MEDIUMS BASED ON INFRARED SPECTROMETRY]. AB - The content of clinically important fatty acids and individual triglycerides in food and biological mediums are traditionally detected by gas and fluid chromatography in various methodical modifications. The techniques are hard-to get in laboratories of clinical biochemistry. The study was carried out to develop procedures and equipment for operative quantitative detection of concentration of fatty acids, primarily palmitic saturated fatty acid and oleic mono unsaturated fatty acid. Also detection was applied to sums ofpolyenoic (eicosapentaenoic and docosahexaenoic acid) fatty acids in biological mediums (cod-liver oil, tissues, blood plasma) using spectrometers of short-range infrared band of different types: with Fourier transform, diffraction and combined scattering. The evidences of reliable and reproducible quantitative detection offatty acids were received on the basis of technique of calibration (regression) by projection on latent structures using standard samples of mixtures of oils and fats. The evaluation is implemented concerning possibility of separate detection of content of palmitic and oleic triglycerides in mediums with presence of water The choice of technical conditions and mode of application of certain types of infrared spectrometers and techniques of their calibration is substantiated PMID- 26999860 TI - [THE MODES OF EVALUATION OF TYPE OF DEHYDRATION IN CHILDREN HOSPITALIZED BECAUSE OF ACUTE INTESTINAL INFECTION]. AB - Every year about 800,000 cases of intestinal infections end in lethal outcome due to dehydration. The different types of dehydration acquire differential approach to correction. Everywhere there is no application of routine detection of osmolarity of blood plasma under exicosis in children in view of absence of possibility of instrumental measurement. The search of techniques is needed to make it possible to indirectly detect types of dehydration in children hospitalized because of acute intestinal infection with purpose to apply rationale therapy of water-electrolyte disorders. The sampling of 32 patients with intestinal infections accompanied with signs of exicosis degree I-III was examined. The detection of osmolarity of blood was implemented by instrumental technique using gas analyzer ABL 800 Flex (Radiometer; Denmark) and five estimate techniques according to results of biochemical analysis of blood. The differences in precision of measurement of osmolarity of blood plasma by instrumental and estimate techniques were compared using Bland-Altman graphic technique. It is established that formula: 2x[Na+kp] + [glucosekp] (mmol/l) is the most recise. Its application provided results comparable with values detected by instrumental mode. PMID- 26999861 TI - [THE POSSIBILITY OF APPLICATION OF COLORIMETRY TECHNIQUE OF DETECTION OF LEVELS OF OXIDATIVE STRESS AND ANTIOXIDANT CAPACITY OF SERUM]. AB - The analysis was implemented concerning indicators of oxidative status and antioxidant capacity of serum. The indicators were received by colorimetry technique based on detection of peroxides in blood serum in examined patients of different categories: healthy persons aged from 17 to 20 years and from 30 to 60 years and patients with bronchopulmonary pathology. The low level of oxidative stress and high antioxidant capacity of serum were established in individuals ofyounger age. With increasing of age, degree of expression of oxidative stress augmented and level of antioxidant defense lowered. Almost all patients with bronchopulmonary pathology had high level of oxidative stress and low level of antioxidant defense. The analysis of quantitative data of examined indicators their conformity with health condition was established PMID- 26999862 TI - [THE SEARCH AFTER PROGNOSTIC TESTS OF DEVELOPMENT OF UROLITHIASIS OF PATIENTS WITH VERTEBRO-CEREBROSPINAL TRAUMA]. AB - The article presents analysis of alterations of biochemical indicators in blood serum and day urine of 22 patients in acute and early periods after vertebro cerebrospinal trauma. Out of total number of patients in 10 (main group) in post traumatic period urolithiasis developed In 12 patients no signs of urolithiasis were detected These examinedpatients were included into comparative group. The reference group was composed with 20 healthy individuals. The concentration of urea, creatinine, uric acid, calcium and inorganic phosphate in blood serum and day urine were detected In patients of main group statistically significant increasing of levels of urea and creatinine was detected in blood serum relative to patients of comparative group. In examined patients of main group clearance of urea was reliably lower than both values of comparative group (up to 2.55 times; p < 0.05) and indicators of reference group (up to 3.75 times; p < 0.05). In patients of this group, clearance of uric acid also had reliable differences from indicators both in comparative group and reference group. Therefore, in patients in acute and early periods of vertebro- cerebrospinal trauma expressed disorders of biochemical indicators of blood serum and urine that can be referred to predictors of risk of development of urolithiasis in the following. The most informative tests were increasing of concentration of urea in blood serum more than 5.30 mmol/l (ratio of likelihood ofpositive test--4.26) and decreasing of clearance of uric acid and urea. PMID- 26999863 TI - [URINE UNDER CHRONIC DYSFUNCTION OF RENAL ALLO-TRANSPLANT]. AB - The study was organized to provide additional characteristic of chronic dysfunction of renal allo-transplant using such biomarkers of serum and urine as enzymes (alanine aminotransferase), aspartate aminotransferase, gamma- glutamiltransferase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase, interleukins (IL-2, IL-8, IL-10), beta-2- microglobulin. The chronic dysfunction of renal allo-transplant is characterized by increasing of concentration of IL-10 and beta-2-microglobulin in serum and increasing of concentration of beta-2 microglobulin, IL-2, IL-8 in urine and increasing of activity of N-acetyl-beta-D glucosaminidase, alkaline phosphatase, aspartate aminotransferase, gamma glutamiltransferase as compared with patients with satisfactory function of renal allo-transplant. The multivariant logistic regression analysis established that only activity of N-acetyl-beta-D-glucosaminidase in urine was reliably independently related to chronic dysfunction of renal allo-transplant. It is assumed that increasing of concentration of beta-2-microglobulin in serum testifies glomerular dysfunction and in urine--tubular dysfunction of renal allo transplant. The enzymeuria indicates continuing damage of epithelium of proximal tubules of nephron. The classification of patients with satisfactory function and chronic dysfunction of renal allo-transplant established that the highest indicators of square under ROC-curves had concentration of beta-2-microglobulin in serum (0.858 +/- 0.061) and urine (0.733 +/- 0.079) and activity of N-acetyl beta-D-glucosaminidase in urine (0.701 +/- 0.061). To specify diagnosis of chronic dysfunction of renal allo-transplant the most useful (ratio of likelihood of positive result 10 and 11 correspondingly) are tests of beta-2- microglobulin in serum (more than 8.55 mkg/ml) and N-acetyl-beta-D-glucosaminidase/creatinine in urine (more than 34 nmol/(sl)/ mmol/l). These discoveries require further validation and confirmation by implementation of morphological analysis of bioptat of renal allo-transplant. PMID- 26999864 TI - [THE TECHNQUE OF FLOW CYTOMETRY IN EVALUATION OF NK-CELLS AND THEIR ACTIVITY]. AB - The review presents main characteristics of human natural killer cells (NK cells), their phenotype and methods of detection of functional activities using flow cytometry. The NK-cells play important role in inherent and adaptive immunity against infections and tumors. Initially these cells were characterized on the basis of capacity to lyse malignant and infected cells without preliminary sensibilization or immunization. The human NK-cells have phenotype CD3-CD56+CD16+ and can be separated in two subpopulations depending on level of expression CD56. The CD56 bright NK-cells predominantly participates immuno-regulation producing cytokines. The CD56dim NK-cells predominantly have cytolytic activity. The NK cells mediate destruction of infected and neoplastic cells through several effector mechanisms: by means of perforins/granzyme containing granules, receptors of apoptosis, antibody-depended cellular mediated cytotoxicity. The cytotoxicicty of NK-cells and production of cytokines provide regulatory role of NK-cells as important participants of adaptive immune system. The NK-cells are fitted with various receptors stimulating and inhibiting their activity. The activation of NK-cells depends on balance between inhibiting and activating receptors. The activation of NK-cells depends on balance between inhibiting and activating receptors. "The golden standard" of detection offunctional activity of human NK-cells is a test of releasing of radioactive chrome from target cells. To apply this technique in clinical practice is not an easy task because of difficulties of utilization of radioactive waste products, short half lifetime, expensiveness and complicated standardization. The article presents cyto fluorimetric techniques for clinical detection of activity of NK-cells. These techniques permit to avoid a number of problems related to application of radioactivity. They also are fast and can be standardized. PMID- 26999865 TI - [THE COMPARATIVE ANALYSIS OF EFFECTIVENESS OF QUICK TESTS IN DIAGNOSTIC OF INFLUENZA AND RESPIRATORY SYNCYTIAL VIRAL INFECTION IN CHILDREN]. AB - The analysis was implemented concerning diagnostic parameters of commercial quick tests (immune chromatographic tests BinaxNOW Influenza A&B and BinaxNow RSV Alere, Scarborough Inc., USA) under detection of antigens of influenza virus A and respiratory syncytial virus in clinical materials. The polymerase chain reaction in real-time and isolation ofviruses in cell cultures. The analysis of naso-pharyngeal smears from 116 children demonstrated that sensitivity and specifcity of detection of influenza virus A using device mariPOC in comparison with polymerase chain reaction made up to 93.8% and 99.0% correspondingly at total concordance of results of both techniques as 98.3%. At diagnosing of respiratory syncytial virus using device mariPOC parameters made up to 77.3%, 98.9% and 862% as compared with polymerase chain reaction. The sensitivity, specificity and total concordance of results of immune chromatographic tests BinaxNOW in comparison ofpolymerase chain reaction made up to 86.7%, 100% and 96.2% correspondingly at detection of influenza virus A and 80.9%, 97.4% and 91.6% correspondingly at detection of respiratory syncytial virus. In comparison with isolation technique in cell cultures sensitivity of system mariPOC and immune chromatographic tests proved to be in 1.3-1.4 times higher at detection of influenza virus A and in 1.7-2 times higher in case of isolation of respiratory syncytial virus. There is no statistically significant differences between diagnostic parameters received for mariPOC and immune chromatographic tests at diagnosing influenza virus A and respiratory syncytial viral infection. PMID- 26999866 TI - [ThE COMPARATIVE CHARACTERISTIC OF PHENOTYPIC AND GENOTYPIC RESISTANCE TO AMINOGLYCOSIDES OF STRAINS STAPHYLOCOCCUS AUREUS ISOLATED IN TRAUMATOLOGICAI ORTHOPEDIC HOSPITAL]. AB - The clinical isolates of Staphylococcus aureus (n = 102) were analyzed on sensitivity and to gentamicin, tobramicin, netimicin and amikacin. The disc diffusing technique was applied. The technique ofpolymerase chain reaction was applied to analyze all strains establishing presence in their genomes genes aac (6'-Ie/aph(2"), ant1, aac, ant(6)-Ia, aph (3')-IIIa and ant(4')-Ia coding amino glycoside-modifying enzymes. The strains sensitive to amino-glycosides had no the given genes in genome. The genome of all strains resistant to amino-glycosides included no less than two of enumerated genes. The 100% correlation was established between phenotypic resistance of analyzed strains to amino-glycosides and availability in them of gene aac(6')-Ie/aph(2"). PMID- 26999867 TI - [THE APPLICATION OF SELECTIVE CHROMOGENIC AGAR FOR DETECTING ENTEROBACTERIA WITH PRODUCTION OF BETA-LACTAMASES]. AB - The detection of enterobacteria with production of beta-lactamases of extended spectrum in selective chromogenic agar was analyzed The results ofdetection of beta-lactamases of extended spectrum was compared with "double disc" technique. The smears from mucous membrane of guttur and rectum from patients were analyzed in parallel on solid growth agar (Endo or Mac Conkey) and on selective agar CHROMagartm ESBL (CHROMagar France). The production of beta-lactamases of extended spectrum was confirmed using "double discs" technique. To exclude hyper production of ampC beta-lactamases E-test was applied containing cefotetan and cefotetan with cloxacillin. The sampling consisted of 1552 samples from patients. The study permitted to isolate 1243 strains of enterobacteria on agar Endo or Mac Conkey and 409 strains of enterobacteria on selective agar CHROMagartm ESBL (Escherichia coli n = 226, Klebsiella pneumoniae n = 105, enterobacter spp. n = 35, Citrobacter spp. n = 21, others n = 22). The application of "double discs" technique confirmed production of beta-lactamases of extended spectrum in 386 (94%) out of 409 strains isolated on agar CHROMagartm ESBL. In 23 (6%) of strains no confirmation was established and hyper-production of ampC of beta-lactamases was established 15 out of total. Additionally, 8 were sensitive to cephalosporin of third generation. All enterobacteria isolated on agar Endo or Mac Conkey also were tested by "double discs" technique. Overall, 394 strains of enterobacteria with production of beta-lactamases of extended spectrum were obtained. On all agars (agar Endo or Mac Conkey and CHROMagartm ESBL)--263 (67%) strains; only on CHROMagartm ESBL--123 (31%) and only on agar Endo or Mac Conkey--8 (2%) (p < 0.0001). The sensitivity of selective agar CHROMagartm ESBL made up to 98% and specificity--97%. The resolution about detection of enterobacteria producing beta lactamases of extended spectrum were submitted to clinic in 18-24 hours after arrival ofsamplesfrom patients in laboratory. The CHR OMagartm ESBL has higher sensitivity and specificity to detect enterobacteria with production of beta lactamases of extended spectrum and can be applied in common laboratory practice. PMID- 26999868 TI - [THE PATHOGENIC POTENTIAL OF MORAXELLA CATARRHALIS AND STAPHYLOCOCCUS EPIDERMIDIS UNDER INFLAMMATORY PROCESSES OF UPPER RESPIRATORY TRACTS]. AB - The frequent isolation from biological material of Moraxella catarrhalis under bronchitis and pneumonia and Staphilococcus epidermidis under rhinitis and sinusitis requires profound investigation offactors ofpathogenicity ofthe mentioned microorganisms. The genetic and phenotypic markers of virulence of strains M. catarrhalis and S. epidermidis are examined. Their etiologic role in development of infection processes of respiratory tract and middle ear is determined The most of M catarrhalis strains isolated under bronchitis and pneumonia have gene mcaP responsiblefor production ofprotein McaP that provides adhesion to epithelium cell of host and lipolitic activity of bacteria. The strains isolated from patients with pneumonia had the most adhesive activity. The cluster of genes ICA with leading role of gene icaA is responsible for for availability offactors of intercellular adhesion in Staphilococci strains. In the clinical samples from patients with sinusitis this gene is detected 5 times more frequently than from healthy individuals. In phenotypic tests, expression of gene icaA in S. epidermidis isolated from patients is three times higher than in strains isolated from healthy individuals. To establish etiologic role of M. catarrhalis and S. epidermidis and to develop tactic of therapy of patients with bronchitis, pneumonia and sinusitis complex approach is needed, including detection of genetic and phenotypic markers of virulence in isolated microorganisms. PMID- 26999870 TI - Advances in the Treatment of Endocrine Disorders in Adolescents. PMID- 26999869 TI - [THE DIAGNOSTIC APPROACHES TO VERIFICATION OF STREPTOCOCCUS INFECTION IN PATIENTS WITH INFECTIOUS MONONUCLEOSIS]. AB - The Rostovskii state medical university of Minzdrav of Russia, 344022 Rostov-on Don, Russia The analysis is applied concerning significance of laboratory techniques of verification of streptococcus infection (bacteriological analysis, detection of anti-streptolysin O in pair serums) in 148 patients with infectious mononucleosis aged from 3 to 15 years. The content of anti-streptolysin O exceeded standard in 41 +/- 4.8% of patients with concomitant in acute period and in 49.5 +/- 4.9% during period of re-convalescence. This data differed from analogous indicator in patients with negative result of examination on streptococcus infection independently of period of disease (9.3 +/- 2.8%). The exceeding of standard of anti-streptolysin O was detected more frequently (t >= 2, P >= 95%) in patients with isolation of Streptococcus pyogenes (56.9 +/- 5.8%) than in patients with Streptococcus viridans (31.2 +/- 6.5%). The concentration of anti-streptolysin 0 in patients with concomitant streptococcus infection varied within limits 200-1800 IE/ml. The minimal level of anti-streptolysin O (C = 200 IE/mI) was detected independently of type of isolated Streptococcus and period of disease. The high levels of anti-streptolysin O were observed exclusively in patients with isolation of Streptococcus pyogenes. In blood serum ofpatient with concomitant streptococcus infection (Streptococcus pyogenes + Streptococcus viridans) increasing of level of anti-streptolysin O was detected in dynamics of diseases from minimal (C = 200 IE/ ml) to moderately high (200 < C < 400 IE/mI). It is demonstrated that to identify streptococcus infection in patients with infectious mononucleosis the anamnesis data is to be considered. The complex bacteriological and serological examination ofpatients is to be implemented This is necessary for early detection ofpatients with streptococcus infection and decreasing risk of formation of streptococcus carrier state. PMID- 26999871 TI - Thyroid Disorders in Adolescents. PMID- 26999872 TI - Update on Diabetes in Children and Adolescents. PMID- 26999873 TI - Update on Puberty and Its Disorders in Adolescents. PMID- 26999874 TI - Bone Health in Adolescence. AB - Osteoporosis occurs during childhood and adolescence as a heritable condition such as OI, with acquired disease (eg, IBD), or iatrogenically as a result of high-dose glucocorticoid therapy. However, the number of children affected by osteoporosis during youth is small compared to the numbers who will develop osteoporosis in adulthood. Prevention of adult osteoporosis requires that an optimal environment for the achievement of peak bone mass be established during the growing years. Detection of low BMD can be achieved using modalities such as DXA and pQCT. Standard radiologic studies, especially vertebral radiography, may also be helpful in children and adolescents at high risk for osteoporosis. It is critical to the development of healthy bones that adolescents have proper nutrition with adequate calcium and vitamin D intake and that they participate in regular physical activity (especially weight-bearing exercise). In the recent past, the dual goals of proper nutrition and exercise were not being achieved by many, if not most, adolescents. Those caring for adolescents should strive to educate teens and their families on the importance of dietary calcium and vitamin D as well as advocate for supportive environments in schools and communities that foster the development of healthy habits with regard to diet and exercise. In order to help identify the population at risk for osteoporosis, a bone health screen with assessment of calcium intake and determination of family history of adult osteoporosis (hip fracture, kyphosis) should be a routine part of adolescent health care. Universal screening of healthy adolescents with serum 25OHD levels is not recommended. Adolescents with conditions associated with reduced bone mass should undergo bone densitometry or other studies as a baseline, and BMD should be monitored at intervals no more frequently than yearly. Although controversy remains regarding the optimum dose of vitamin D for treatment of osteoporosis, all would agree that vitamin D should be provided, and in doses somewhat higher than previously recommended. Excessive vitamin D should be avoided. The use of bisphosphonates is recommended for the treatment of OI, as well as for treatment of select children with severe osteoporosis associated with chronic conditions that lead to frequent or painful fragility fractures. In such situations, bisphosphonates should be prescribed only in the context of a comprehensive clinical program with specialists knowledgeable in the management of osteoporosis in children. PMID- 26999875 TI - Polycystic Ovarian Syndrome. PMID- 26999876 TI - Adrenal Dysfunction. PMID- 26999877 TI - Screening and Treatment of Common Lipid Disorders in Adolescents. AB - Cardiovascular disease remains a substantial health care burden in the adult population, the roots of which begin in childhood. Universal screening for dyslipidemia in all children and adolescents has been implemented to identify cases of FH that are otherwise missed by conventional screening because untreated FH can result in early CVD and untimely death. Recommendations for medical therapy did not change with the 2011 NHLBI guidelines. LDL levels targeted for therapy usually are elevated because of primary genetic disorders such as FH. Although these recommendations remain controversial, the benefit of universal screening and subsequent treatment of high-risk patients far outweighs the risk of not screening, although more investigation is warranted to understand the long term outcomes of CVD risk in youth. PMID- 26999878 TI - Prevention and Management of Pregnancy in Adolescents with Endocrine Disorders. AB - Because 83% of adolescent pregnancies among teens 15 to 19 years old are unintended and because adolescents with chronic medical conditions are as likely to be sexually involved as are healthy teens, preventing unintended pregnancies among teens with chronic endocrine conditions, including diabetes mellitus (both types 1 and 2), PCOS, and thyroid dysfunction, is critically important. Evidence based guidelines are available to assist with assessment of the risks versus the benefits of specific options for contraception in teens with these and other medical conditions. In many teens, including those with chronic medical conditions, the top-tier contraceptive methods--implants and intrauterine devices -represent the most effective, safest, and most successful contraceptive options for adolescents. Prepregnancy counseling can be an important tool for managing chronic endocrine conditions and lowering the risks for both mother and fetus, but it is underutilized among all women, particularly adolescents. The management of pregnancies complicated by DM, PCOS, and thyroid conditions is facilitated by a coordinated effort among obstetricians, endocrinologists, dietitians, and nurse educators. Primary physicians should be aware of their potential role in preventing unplanned pregnancies among all adolescents, but particularly among those with chronic medical conditions. PMID- 26999879 TI - Endocrine Abnormalities in Patients with Eating Disorders. PMID- 26999880 TI - Turner Syndrome and Klinefelter Syndrome. PMID- 26999881 TI - Disorders of Sex Development: Why Adolescent Medicine Specialists Should Care. PMID- 26999882 TI - Endocrine Consequences of Treatment for Childhood Cancer. PMID- 26999883 TI - Equipoise and orthodontic research?. PMID- 26999884 TI - Obituary. Lawrence Smart AM 1928 -2015. PMID- 26999885 TI - The effect of smiling on facial asymmetry in adults: a 3D evaluation. AB - BACKGROUND/AIMS: Mild resting facial asymmetry exists in clinically symmetrical faces, but the effect of smiling on the magnitude of overall facial asymmetry in adults has not been assessed. The aim of the present study was to use stereophotogrammetry to quantify the effect of smiling on overall facial asymmetry in Caucasian adults who presented with Class I incisor relationships and no history of orthodontic treatment. METHODS: Twenty male and 20 female Caucasians aged 1 8-30 years with no history of orthodontic treatment, a clinically symmetrical face and a Class I incisor relationship had 3D stereophotogrammetric images captured at rest and on natural and maximal smile (T1). The images were repeated 2-4 weeks later (T2) to assess expression reproducibility. Overall facial asymmetry scores were produced from 27 landmarks using partial Ordinary Procrustes Analysis (OPA) and assessed by an Analysis of Covariance (ANCOVA) model. A random sample of the images was re-examined two months later to calculate intraobserver landmark reproducibility. RESULTS: Mean landmark error was low (0.41 +/- 0.07 mm). Mean overall facial asymmetry scores were not significantly gender different (p = 0.5300); therefore, the male and female data were pooled. Mean overall facial asymmetry scores for maximal (0.91 +/- 0.16) and natural smile (0.88 +/- 0.18) were higher than at rest (0.80 +/- 0.17) (p < 0.0001) and were reproducible across (T1-T2) sessions (p = 0.3204). CONCLUSIONS/IMPLICATIONS: Overall 3D facial asymmetry scores for the sampled Caucasian adults with clinically symmetrical faces increased in magnitude from rest to natural and to maximal smile. Clinicians should assess overall facial asymmetry at rest and on natural and maximal smile at baseline, during treatment and as part of a core outcome assessment, particularly for cases with unilateral posterior crossbite, unilateral cleft lip and palate or skeletal asymmetry. PMID- 26999886 TI - A study of Class III treatment: orthodontic camouflage vs orthognathic surgery. AB - AIM: To evaluate the differences in pretreatment and post-treatment characteristics of Class III patients treated with orthodontic camouflage or orthognathic surgery, and to compare the range of skeletal, dental and soft tissue changes that are likely to occur with treatment, with particular reference to the influence of extractions on the resultant incisor angulations. METHOD: Pretreatment and post-treatment cephalograms of 31 Class III orthodontically camouflaged patients and 36 Class III surgical patients (without genioplasty) were obtained from one specialist practice. From the surgical group, 26 pre surgical lateral cephalograms were also obtained. Inclusion criteria for the two groups were at least three of the following: (1) an ANB angle of 1 degree or less, (2) a Wits appraisal less than -4 mm, (3) an incisal overjet <= 0 mm, and (14) a Class III molar relationship. All lateral cephalograms were traced and digitised and a number of skeletal, dental and soft tissue variables were measured. The camouflage and surgical groups were also divided into premolar extraction and non-extraction subgroups to allow for a specific analysis of extraction effects. RESULTS: Before treatment, the surgical group demonstrated, on average, a more severe skeletal discrepancy and increased dental compensations, compared with the orthodontically camouflaged group. After treatment, the mean SNA angle was greater, the ANB angle was more positive, the Wits appraisal was closer to ideal and the lower incisors were less retroclined in the surgery group. There was a small mean reduction in horizontal chin projection in the surgery group compared with a small increase in the camouflage group. The mentolabial fold and the lower lip curve were deeper, on average, and the lips less retrusive after surgery. There was a mean increase in upper incisor proclination during treatment in both the surgical and camouflage groups with a greater increase in the camouflage group. There was a significant reduction in upper incisor proclination and a subsequent greater increase in the ANB angle associated with upper premolar extractions in the surgical group compared with the non-extraction group. Lower premolar extractions in the camouflage group resulted only in a deeper mentolabial fold compared with those treated without lower extractions. CONCLUSIONS: Class III patients selected for surgical treatment are likely to have more severe pretreatment dental and skeletal discrepancies than those selected for camouflage treatment. Surgical treatment is associated with significant decompensation of the lower incisors but, ultimately, not the upper incisors. Class III patients treated with either camouflage or surgery treatment are likely to finish with slightly proclined upper incisors. Generally, surgical treatment results in greater skeletal change, involving normalisation of the skeletal base relationship, a reduction in chin prominence, fuller lips, and a more favourable lip and chin contour. PMID- 26999887 TI - A multi-centre evaluation of multiple supernumerary premolar prevalence. AB - AIM: The occurrence of multiple supernumerary teeth is rare and often found in association with syndromes such as cleidocranial dysplasia, Gardner's syndrome or cleft lip and palate. Few examples of non-syndromal multiple supernumerary teeth have been reported. The aim of this multi-centre study was to investigate the prevalence of supernumerary premolar teeth in non-syndromic patients and to investigate the association between the presence of supernumerary premolar teeth and malocclusion type in a Turkish population. MATERIALS AND METHODS: The clinical records and panoramic radiographs of 10,700 patients (referred to three different university hospitals) were retrospectively examined for the presence of supernumerary premolars. Age, gender, orthodontic malocclusion type, the number of supernumerary premolars (two or more), the distribution, location, position (vertical, horizontal, inverted, mesio-angular), surgical approach, and related complications (pain, cystic changes, root resorption, or eruption disturbance of adjacent teeth) were recorded. RESULTS: Forty-two cases (13 Class I, 17 Class II, 12 Class III) of multiple mandibular supernumerary premolars in patients without an associated syndrome were detected. A total of 97 (27 Class I, 41 Class II, 29 Class III) supernumerary premolar teeth were found, with a prevalence of 0.39%. No statistical difference was found related to gender, malocclusion type and supernumerary premolars (p > 0.05). The majority of the extra premolars were located in the mandible, which was statistically significant (p < 0.05). CONCLUSION: The present study revealed that the prevalence of multiple supernumerary teeth was 0.39%. The most frequently impacted premolars were found in the mandible and more often associated with Class II malocclusions in the examined Turkish population. PMID- 26999888 TI - A comparison of orthodontic treatment outcomes using the Objective Grading System (OGS) and the Peer Assessment Rating (PAR) index. AB - INTRODUCTION: The use of objective criteria is essential to uniformly quantify and measure the severity of malocclusions and the efficacy of different treatment modalities. The Peer Assessment Rating (PAR) index and, more recently, the American Board of Orthodontics Objective Grading System (OGS) were developed to fulfill this need. AIM: The aim of this retrospective study was to assess and compare treatment outcomes using the UK and US weighted PAR and the OGS. MATERIALS AND METHODS: The sample consisted of randomly selected records of 50 patients treated by residents in one postgraduate orthodontic clinic. UK and US weightings for the PAR index were applied and compared with OGS. RESULTS: There was no statistically significant association between the OGS and the PAR index grading systems. Neither the UK nor the US PAR weightings showed statistically significant correlation with the OGS. All cases were 'greatly improved' or 'improved' according to the PAR index, while most cases (62%) failed according to OGS. There was a statistically significant correlation between the unweighted PAR index and the OGS (r = -0.32, p = 0.024). The US and the UK weightings for the PAR were highly correlated (r = 0.90, p < 0.001). Both weighting systems were also highly correlated with the unweighted PAR (p < 0.001). There were no gender differences found in any of the scoring systems. CONCLUSIONS: The current PAR index cannot replace the OGS for evaluating treatment outcomes. The current OGS cannot detect the improvement achieved in a treated case. PMID- 26999889 TI - Chemical and mechanical characteristics of contemporary thermoplastic orthodontic materials. AB - AIM: The aim of the present study was to characterise the chemical and mechanical properties of contemporary thermoplastic orthodontic materials. MATERIALS AND METHODS: Four thermoplastic materials were tested: Clear Aligner (Scheu-Dental), ACE and A+ (Dentsply), and Invisalign (Align Technology). Eight appliances were fabricated from each material and a small portion from each was analysed by ATR FTIR spectroscopy. The appliances were cut and, following metallographic grinding and polishing, were subjected to instrumented indentation testing (IIT) employing a Vickers indenter. Martens Hardness (HM), Indentation Modulus (E(IT)), Elastic to Total Work Ratio (elastic index (eta(IT))) and Indentation Creep (C(IT)) were determined according to ISO 14577-1. The mean values of the mechanical properties were statistically analysed by one way ANOVA and Tukey Kramer multiple comparison test at a = 0.05. RESULTS: ATR-FTIR analysis identified that Invisalign was a polyurethane-based material, whereas the others were based on polyester, polyethylene glycol terephthalate (PETG). Invisalign showed higher hardness and modulus values, a slightly higher brittleness and lesser creep resistance compared with the PETG-based products. CONCLUSIONS: The materials tested showed significant differences in their chemical structure and mechanical properties and therefore differences in their clinical behaviour are anticipated. PMID- 26999890 TI - Comparative evaluation of pulpal blood flow during incisor intrusion. AB - AIM: The aim of the present study was to evaluate and compare changes in pulpal blood flow (PBF) as a result of maxillary incisor intrusion achieved by one of two methods (utility arches or mini-implants). MATERIALS AND METHODS: Thirty subjects were divided into three groups, the first of which underwent maxillary incisor intrusion using utility arches (UA) and a second group, intrusion via mini-implants (MI). The third group acted as a control. An intrusive force of 100 g was applied to the upper incisors in the treatment groups, whereas no force was applied to the anterior teeth in the control group. A laser Doppler flowmeter (LDF) was used to measure PBF at baseline (T0) and during incisor intrusion at 24 hours (T1), three days (T2), seven days (T3) and three weeks (T4). Statistical changes in PBF were assessed by the Wilcoxon Signed Rank and Mann-Whitney U tests, with significance set at p < 0.05. RESULTS: The mean PBF in the UA and MI groups decreased significantly from T0 to T1 (p < 0.001), slightly increased at T2 and continued to increase gradually at T3. PBF attained levels similar to those measured prior to intrusion at T4. No significant changes in PBF were observed in the control group over the course of the study. The only statistically significant difference between the UA and MI groups were at T1 and T2, at which time the MI group had lower PBF values (p < 0.001). CONCLUSIONS: Despite slight regressive changes in pulpal tissue observed over the short-term, PBF values tended to return to initial levels within three weeks, indicating that changes observed in PBF with the UA and MI intrusion methods are reversible. Although the changes in PBF could not be directly related to the method of intrusion employed, in general, a more severe drop in PBF was observed in the MI group during the first three days of intrusion. PMID- 26999891 TI - Shear bond strength of different fixed orthodontic retainers. AB - OBJECTIVE: To compare the shear bond strength of different fixed retainer wire diameters bonded using a conventional composite resin or a specific retainer composite. MATERIALS AND METHODS: One-hundred-and-twenty extracted human premolar teeth were divided into six groups. After conventional acid etching with a 37% phosphoric acid gel for 30 seconds, twist flex wires of various diameters (0.0175", 0.0215", 0.032") were bonded as fixed retainers. Conventional bracket adhesive (Filtek Z250) or retainer specific adhesives (Transbond LR) were used. After curing, the specimens were stored for 24 hours in distilled water at 37 degrees C and, thereafter, subjected to 500 thermal cycles. The specimens were then debonded using a Universal Instron machine. The site of failure was recorded for each specimen and the shear bond strength calculated. Statistical analyses were provided using a Chi-square test for failure site and a two-way ANOVA test to assess shear bond strength. RESULTS: The site of failure was predominantly at the wire composite interface in all groups. The specific retainer composite showed a significantly higher shear bond strength compared with conventional composite (p < 0.001). There was a statistically significant difference between the three wire diameters (p < 0.001); the 0.0215" wire had the highest shear bond strength, whereas the 0.032" wire had the least shear bond strength. CONCLUSIONS: The site of failure was unrelated to wire diameter or adhesive. The optimal combination to maximise the bond strength of fixed retainers appeared to be a specific retainer adhesive and a wire diameter of 0.0215". PMID- 26999892 TI - Skeletal effects of the alteration of masseter muscle function. AB - AIM: To investigate the effects of muscle denervation and the introduction of the beta2-adrenoceptor agonist, formoterol, on the relationship between muscles and underlying skeletal growth. METHOD: Thirty-one (4-week-old) male Sprague-Dawley rats were assigned to four groups: Surgical Sham; Denervated; Denervated + beta2 agonist; and beta2-agonist only. The Surgical Sham group had the left masseteric nerve exposed but not sectioned. Both of the denervated groups had the left masseteric nerve exposed and sectioned. The groups receiving the beta2-agonist had formoterol directly injected into the left masseter muscle every three days for eight weeks. Sixteen angular and linear skeletal measurements were assessed in the overall craniofacial region and the mandible via standardised digital radiography in three views: lateral head, submento-vertex and right and left disarticulated hemi-mandibles. RESULTS: The findings indicated that, following surgical denervation of the masseter muscle, there were significant changes in the muscle and in the subsequent development of the underlying skeletal structures. The post-surgical changes were largely offset by the administration of a beta2-agonist, formoterol, which attenuated muscle atrophy. However, the administration of the beta2-agonist only, without surgical denervation, did not lead to changes in skeletal facial form. CONCLUSIONS: Denervation atrophy of the masseter muscle results in statistically significant changes in the development of the underlying skeleton. The changes, however, are localised to areas of muscle attachment. The administration of the beta2-agonist, formoterol, despite its effect on muscle anabolism, does not have a significant effect on underlying skeletal growth. PMID- 26999893 TI - The effect of the buccal corridor and tooth display on smile attractiveness. AB - AIMS: The aim of the present study was to evaluate the lay perception of the effect of the buccal corridor and amount of tooth-gingival display on the attractiveness of a smile in different facial types. MATERIALS AND METHODS: Using Adobe Photoshop CS3 software, frontal facial images of two smiling Iranian female subjects (one short-faced and one long-faced) were altered to create different magnitudes of buccal corridor display (5, 10, 15, 20 and 25%) and tooth-gingival display (2 mm central incisor show, 6 mm central incisor show, total central incisor show, total tooth show with 2 mm gingival show and total tooth show with 4 mm gingival show). Sixty Iranians (30 males and 30 females) rated the attractiveness of the pictures on a 1-5 point scale. RESULTS: Narrower smiles were preferred in long-faced subjects compared with short-faced subjects. Minimal tooth show was more attractive than excessive gingival display in short-faced subjects. There were no gender specific, statistically significant differences found in the ratings given by the lay assessors. CONCLUSIONS: Harmonious geometry of the smile and face in both the vertical and transverse dimensions influences smile attractiveness and this should be considered in orthodontic treatment planning. PMID- 26999894 TI - Bond strength and micro-computed tomographic evaluation of pre-coated brackets. AB - OBJECTIVES: The aim of the present study was to assess and compare the shear bond strength (SBS) of metal pre-coated orthodontic brackets bonded to fluorotic and non-fluorotic teeth treated with three different etching techniques. A second aim was to determine the volume of adhesive remaining on the tooth at debond using micro-computed tomography (MUCT). METHODS: Ninety extracted premolars were selected to include 45 fluorotic (test group) and 45 non-fluorotic (control group) teeth. Each group was divided into three subgroups of 15 each, which were treated as follows: 1) micro-etched; 2) acid-etched; and 3) both micro-etched and acid-etched. A bonding agent was applied to the prepared surfaces; pre-coated and light-cured brackets were attached to all teeth. An Instron universal testing machine was used to record the debonding force. Specimens were then scanned using a microCT to evaluate the amount of adhesive remaining on the teeth. The significance of the statistical tests was pre-determined at p < 0.05. RESULTS: Two-way ANOVA showed that fluorosis of teeth had no influence on the SBS (p = 0.165) whereas the volume of adhesive remnants was significantly higher in the control group compared with the test group (p < 0.001). CONCLUSIONS: Fluorosis had no influence on the SBS of brackets, whereas it had a negative influence on retaining adhesives onto the tooth surfaces. PMID- 26999895 TI - Closure of an open bite using the 'Mousetrap' appliance: a 3-year follow-up. AB - Recently, skeletal anchorage devices have been used as anchorage units for upper molar intrusion as a way of correcting an anterior open bite malocclusion. To avoid the surgical procedures associated with the placement of miniplates in the zygomatic area, mini-implants may be inserted palatally or buccally in the alveolar process. However, consideration must be given to the potential risks of root damage and a higher failure rate associated with the placement of temporary anchorage devices (TADs) in the interradicular area. The anterior hard palate provides a safer and more stable alternative for TAD placement. The current paper describes the biomechanical principles and the clinical procedures of 'Mousetrap' mechanics using mini-implants in the anterior palate for upper molar intrusion. The stomatognathic response of maxillary molar intrusion is an autorotation of the mandible and so the sagittal implications for each patient must be considered. The presented patient demonstrates successful correction and stability of the treatment result at a three-year review. PMID- 26999896 TI - Multi-disciplinary management of a patient with a post-traumatised incisor presenting concurrent replacement and inflammatory resorption: a case report. AB - This case report describes the multidisciplinary management of a young male who presented with a Class I incisor relationship and bi-maxillary dento-alveolar protrusion on a Class I skeletal base. The occlusion was complicated by an ankylosed and moderately infra-positioned upper left permanent central incisor, an anterior crossbite, crowding, a reduced overbite and centreline discrepancy. The incisor was traumatised and avulsed when the root was immature and the tooth was reimplanted with delay. On referral for orthodontic treatment at age 11 .5 years, the upper left central incisor was experiencing ankylosis-related (osseous replacement) resorption and external root resorption simultaneously. Aside from the orthodontic aims, it was important to address the disrupted alveolar development to facilitate later prosthodontic replacement of the upper left permanent central incisor by idealising the inter-coronal and inter-radicular spaces. Treatment consisted of fixed orthodontic appliances in conjunction with the extraction of all second premolars and the upper left permanent central incisor with episodic surgical curettage. An upper Hawlix retainer was provided immediately at debond and a cantilevered resin-retained bridge was placed four months later. PMID- 26999897 TI - Class III orthognathic surgical cases facilitated by accelerated osteogenic orthodontics: a preliminary report. AB - OBJECTIVES: To describe a multidisciplinary treatment approach that includes corticotomy, orthodontic force and orthognathic surgery for the management of skeletal Class III surgical cases. The main advantage of the combined techniques is a reduction in treatment time for young adult patients. METHOD: Accelerated Osteogenic Orthodontics (AOO) was delivered to three young adult patients during their pre-surgical orthodontic treatment. After aligning and levelling the dental arches, a piezosurgical corticotomy was performed to the buccal aspect of the alveolar bone. Bone graft materials were used to cover the decorticated area and soft tissue flaps were replaced. RESULTS: The mean time for extraction space closure was 5.4 +/- 1.3 months and the mean time for pre-surgical orthodontic treatment was 12.0 +/- 0.9 months. The average total treatment time was 20.4 +/- 2.4 months. A pre-existing bony fenestration in the buccal cortex adjacent to the right lateral incisor root apex of Case 1 was corrected. CONCLUSION: The facial aesthetics of three patients improved following multidisciplinary treatment. This approach may be an efficient method for the orthognathic patient who desires a reduced treatment time, but further clinical research is required. PMID- 26999898 TI - An aesthetic approach towards the temporary restoration of missing upper lateral incisors during orthodontic treatment. PMID- 26999899 TI - The importance of early parental support. PMID- 26999900 TI - 'Shameful' lack of support for abuse victims, says NSPCC. PMID- 26999901 TI - The power of couple-focused approaches in the perinatal period. PMID- 26999902 TI - Light after darkness. PMID- 26999903 TI - Pregnancy and eczema. PMID- 26999904 TI - Demonstrating effective support to parents with learning disabilities. Part 2. PMID- 26999905 TI - 'Early intervention is key to reducing domestic abuse'. PMID- 26999906 TI - The future looks app-y. PMID- 26999907 TI - The NCMP--time to extend, or call a halt? PMID- 26999908 TI - Is the obesity crisis the biggest threat to our children's health? PMID- 26999909 TI - A New Way of Learning. PMID- 26999910 TI - Longitudinal Integrated Clerkship: A Student's Perspective. PMID- 26999911 TI - False Negative Urine Pregnancy Testing with Complete Molar Pregnancy: An Example of the Hook Effect. AB - INTRODUCTION: Gestational trophoblastic disease (GTD) encompasses a group of tumors derived from trophoblasts, which normally form the placenta during pregnancy. Human chorionic gonadotropin (hCG) is a glycoprotein composed of an alpha subunit identical to that of thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Detection of beta-hCG is achievable in both urine and serum samples, proving useful for the detection of normal pregnancy and GTD. However, in the presence of very high levels of beta hCG, a false negative result may be obtained due to a phenomenon called the "hook effect" or "prozone phenomenon." In certain circumstances, trophoblastic tumors can produce very high levels of beta-hCG, causing misleading results on urine pregnancy testing. CASE PRESENTATION: A 49-year-old Caucasian female with past medical history pertinent for deep vein thrombosis, ovarian cysts, and osteopenia presented to her internist with report of irregular uterine bleeding for the preceding three months, accompanied by complaints of abdominal bloating, night sweats, and constipation. The patient stated she had completed two negative qualitative urine pregnancy tests and had been seen by both gynecology and gastroenterology, with recommendations to start supplemental estrogen for her symptoms and begin additional fiber intake for irritable bowel syndrome, respectively. Despite negative urine beta-hCG, a quantitative serum beta-hCG was obtained and revealed a level greater than 200,000 international units (IU). The patient was referred to gynecologic oncology and an open abdominal hysterectomy with preservation of her ovaries was performed. Histopathologic examination showed a complete hydatiform mole with no evidence of invasion. CONCLUSION: The case highlights the importance of clinical judgment in modern medicine, where biochemical methods and imaging modalities have become main stays in diagnosis. As mentioned, there are ways to reduce the incidence of the hook effect, but with added time and cost. Clinicians need to consider the possibility of the hook effect for instances where the clinical picture points to a disease entity despite negative test results. Delaying diagnoses, as illustrated with GTD, has the potential to cause significant morbidity and mortality. PMID- 26999912 TI - The Effects of Food Deserts on the Weight Status of South Dakota Children. AB - INTRODUCTION: Childhood obesity continues to be a public health issue in the U.S. Research prior to this study demonstrated that children living on food deserts (FD) had greater weight statuses than children who did not live on FDs. Based on U.S. Department of Agriculture classification, almost half of the state of South Dakota is classified as a food desert, and childhood obesity continues to be an issue in the state. The purpose of this study was to determine if FDs play a role in childhood obesity in South Dakota, more specifically whether South Dakota children who live on FDs or on the border of FDs have greater weight statuses than children who live on non-FDs. METHODS: School height and weight data collected by the South Dakota Department of Health was used to calculate weight status for students in six schools; weight was categorized as underweight, healthy weight, overweight, and obese. RESULTS: It was discovered that the pair of border-FD areas had the lowest total percentage of students who were classified as obese while the non-FD areas had the highest percentage of students who were classified as obese. The FD areas fell in between the aforementioned areas. CONCLUSIONS: By utilizing this research and identifying precursors for obesity, such as where an individual lives and their access to healthy food, health care leaders and their multidisciplinary team can help facilitate community interventions that target areas most impacted by childhood obesity. PMID- 26999913 TI - Propionibacterium Acnes Brain Abscess in an Immunocompetent Man in the Absence of Prior Neurosurgery. AB - Propionibacterium acnes is a rare, but established, cause of intracranial abscesses. We describe a case of P. acnes brain abscess in an immunocompetent man without prior neurosurgery. A 49-year old man with mild psoriasis presented with a two-week history of gait changes, generalized weakness and a two-day history of headaches, aphasia and confusion. Imaging revealed a left thalamic mass and surgical biopsy suggested a pyogenic abscess. Cultures of biopsy samples of the abscess grew P. acnes alone. MRI and serial neurological exam showed marked clinical improvement with intravenous antibiotics. The significant reduction in the abscess was sustained on MRI obtained at six weeks after completion of antibiotic therapy. In conclusion, P. acnes must be considered as a differential diagnosis in individuals presenting with features suggestive of a brain abscess even in the absence of immunosuppression or previous neurosurgery. PMID- 26999914 TI - Mitral Stenosis Presenting as Asthma. AB - Although wheezing is one of the most common symptoms and physical findings in asthma, other causes of wheezing should be kept in mind: vocal cord dysfunction, postnasal drip syndrome, chronic obstructive pulmonary disease, bronchiectasis, and non-pulmonary diseases, like heart failure and pulmonary edema. Here, we present a case of severe mitral stenosis with pulmonary edema treated for resistant asthma. If asthma is difficult to control, other etiologies of wheezing, including cardiac disease, should be taken into consideration during diagnosis. PMID- 26999916 TI - New Insulin Options for Diabetic Patients. PMID- 26999917 TI - DAKOTACARE Update: Business As Usual. PMID- 26999915 TI - Update on Adolescent Immunizations. AB - Timely and complete adolescent vaccination remains an elusive public health goal. Three infections for which routine adolescent vaccination is recommended in the U.S. are pertussis, meningococcal disease and human papillomavirus (HPV). These infections and the Tdap, meningococcal and HPV vaccines recommended for adolescents are reviewed in this article. PMID- 26999918 TI - Quality Focus: Sepsis Now Required for Hospital Inpatient Quality Reporting Program. PMID- 26999919 TI - Patient Education: Wintertime Recharge. PMID- 26999920 TI - [Comparative study of adverse events between a posterolateral and a direct lateral approach for uncemented primary hip arthroplasty in patients over 65 years of age with femoral neck fractures]. AB - INTRODUCTION: Femoral neck fractures represent an important chapter in the practice of Traumatology, due to their high incidence, mainly among patients over 65 years of age; they account for around 65% of surgeries in Traumatology. Early function of patients who sustained a femoral neck fracture is of the utmost importance, as survival decreases within the first 12 months. The purpose of this paper is to compare the intra- and postoperative course of patients who underwent primary hip surgery using Hardinge's direct lateral approach versus Moore's posterolateral approach. MATERIAL AND METHODS: 79 patients over 65 years of age with femur fractures were selected and divided into 2 groups according to the approach used. Hardinge's direct lateral approach was used in 32 patients and Moore's posterolateral approach in 47 patients, from March 2011 to April 2013. RESULTS: Considering the variables studied, a statistically significant difference (p < 0.005) was seen in the number of blood units transfused to patients in whom Hardinge's direct lateral approach was used. CONCLUSIONS: We agree with the literature in that there is a significant difference in the intra- and post-operative course of patients with femur neck fractures managed using Hardinge's direct lateral approach. A statistically significant difference was seen in the number of blood units transfused per patient, something that in our setting represents better resource utilization. PMID- 26999921 TI - [Prevalence of hip, femur and knee fractures at the High Specialty Medical Unit, Hospital de Traumatologia y Ortopedia "Lomas Verdes", Instituto Mexicano del Seguro Social]. AB - BACKGROUND: Lower limb fractures are more frequent among older patients with osteopenia after a low energy fall and/or among young patients who sustain a high energy trauma. The prevalence of hip, femur and knee fractures at the High Specialty Medical Unit, Hospital de Traumatologia y Ortopedia "Lomas Verdes" is unknown. MATERIAL AND METHODS: Cross-sectional study, descriptive and retrospective design. Cases with low extremity fractures treated from January 1st, 2012 to December 31st, 2013 at the Hip, Femur and Knee Service, High Specialty Medical Unit, Hospital de Traumatologia y Ortopedia "Lomas Verdes", were reviewed. RESULTS: Most patients (52.2%) were females; 64.1% of patients were over 60 years of age. Fracture distribution according to the segment involved was as follows: 73.4% (n = 1,327) were femur fractures, 13.5% (n = 244) tibial plateau fractures, and 13.2% (n = 238) patellar fractures. 66.8% (n = 1,209) of patients had a long hospital stay (more than 10 days). According to the anatomical location of fractures, transtrochanteric fractures (49.1%) were the most frequent ones, followed by patellar fractures (13.2%), and femur shaft fractures (12.7%). CONCLUSIONS: The prevalence of lower limb fractures at our hospital corresponds to what has been reported internationally. PMID- 26999922 TI - [Frequency of musculoskeletal pathology among elderly patients and its treatment at a Private Hospital in Mexico City]. AB - BACKGROUND: The elderly represent a growing sector of the Mexican population and they are expected to outgrow the number of youths in the coming years. Musculoskeletal conditions are a major cause of disability among the elders; they affect up to 80%. In Mexico City 36% of the population uses private health care services. OBJECTIVE: To contribute with epidemiologic data about the frequency of musculoskeletal conditions and their hospital-based treatment in patients ages 65 and over admitted to a private hospital in Mexico City. MATERIAL AND METHODS: Male and female patients ages 65 and over, admitted for a musculoskeletal illness. RESULTS: 390 patients were studied; 276 females and 114 males. The age group 65-69 years was predominant. The predominating musculoskeletal conditions included fractures, which represented 29.4%, and gonarthrosis, 23.30%. Patients were treated surgically accounted for 91.02%. CONCLUSION: Among the elderly, chronic conditions are more frequent than acute ones; however, fractures are the most frequent diagnosis. There are no studies in Mexico analyzing the frequency of both, traumatic or degenerative conditions, and their treatment in elderly patients admitted to a private hospital. These results will therefore provide epidemiologic information about our population. PMID- 26999923 TI - [Comparative study between plate-graft, cage-plate and peek cage in cervical arthrodesis for cervical stenosis]. AB - INTRODUCTION: A variety of systems have been developed to fix and perform arthrodesis of the cervical spine, with the advantages of reducing the risk of pseudoarthrosis, extrusion and graft collapse and achieving a more precise sagittal alignment. We therefore need to compare the results of the following approaches to patients with cervical stenosis: plate-graft, cage-plate and PEEK cage. MATERIAL AND METHODS: Prospective, interventional, comparative trial involving three groups: group I, arthrodesis with plate-graft; group II, cage plate, and group III, PEEK cage. The pre- and postoperative assessments included the cervical disability scale, the pain visual analog scale (VAS), and cervical spine X-rays. The results were analyzed with non-parametric tests such as the Wilcoxon sign test and the Kruskal-Wallis test for the comparison of more than two groups. Significance level was 0.05. RESULTS: The sample included a total of 37 patients: n = 12 in group I, with 22 levels; n = 11 in group II, with 19 levels, and n = 14 in group III, with 25 levels. Patient age ranged between 60 and 80. One year after surgery there was an improvement in cervical disability and the pain VAS score, with a statistically significant difference among the three groups (p = 0.001). However, radiographic measurements at that time showed a significant improvement in segmental lordosis (p = 0.02) only in plate-graft patients. CONCLUSIONS: The plate-graft approach provides better clinical and radiographic results compared to the cage-plate and PEEK cage techniques, at the one-year follow- up. PMID- 26999924 TI - [Postoperative pain control with intrathecal morphine in patients undergoing vertebral fusion with instrumentation]. AB - BACKGROUND: Proper postoperative pain management in patients undergoing vertebral arthrodesis with instrumentation is essential to reduce postoperative morbidity and mortality. Intrathecal morphine may provide effective analgesia minimizing the dose required and adverse side effects. The objective of this study is to assess the efficacy of intrathecal morphine to control postoperative pain in patients undergoing vertebral arthrodesis with instrumentation. MATERIAL AND METHODS: A prospective randomized trial was conducted; it included 46 patients who underwent vertebral fusion with instrumentation. Patients were randomly divided into two groups: one of them received a 0.003 mg/kg dose of intrathecal morphine before closing the surgical wound. The following parameters were recorded during the postoperative period: respiratory rate, PCO2, PO2, need for adjuvant anesthesia and subjective pain assessment with the visual analog scale (VAS), at 6, 24 and 48 hours after the surgery. The results were analyzed with non-parametric tests. RESULTS: Patients who received intrathecal morphine had a statistically significant decrease in postoperative pain within 48 hours after the surgery, with a mean VAS score close to 3. In 24.1 percent of patients had complications associated with the use of morphine chloride, such as nausea and vomiting, without any statistically significant differences compared with the control group. CONCLUSIONS: Intrathecal morphine is a safe and effective treatment option to control early postoperative pain in patients undergoing vertebral fusion with instrumentation. This leads to a more convenient and quick recovery. PMID- 26999925 TI - [Comparative study between plate-graft, cage-plate and peek cage in cervical arthrodesis for cervical stenosis]. AB - BACKGROUND: In Mexico low back pain is a very frequent symptom in the orthopedic practice. It is an important cause of work absenteeism, it is difficult to diagnose due to its various etiologies, and its treatment should be carefully chosen as, according to the World Health Organization, only 4% of patients require surgery. OBJECTIVE: To determine the frequency of low back pain at Hospital Angeles Mocel during a two-year period, and analyze the various etiologies and the treatment provided to patients. MATERIAL AND METHODS: The data base of the Orthopedics and Traumatology Service at Hospital Angeles Mocel was analyzed. It consisted of 246 patients over'18 years of age admitted with a diagnosis of low back pain. Frequency, sex, age, etiology and treatment were analyzed. RESULTS: At this hospital low back pain ranks second among the causes for hospital admission at the Orthopedics and Traumatology Service. Frequency is 13.5%; the most frequent age group affected is 31-45 years (36.9%); females were predominant (53.6%). Most cases admitted for low back pain were acute and had a posttraumatic etiology (90% of cases). CONCLUSION: Low back pain is a frequent reason for visiting the doctor worldwide. Epidemiologic studies about the frequency, etiology and treatment of low back pain are scarce in Mexico, even though it is one of the major causes for hospital admission at a private hospital. PMID- 26999926 TI - [Extraarticular hip impingement: Case report]. AB - Femoroacetabular impingement is the mechanical contact between the femur and the pelvis, frequently between the femur neck and the acetabular rim, whether due to a deformity of the former (cam type) or the latter (pincer type). However, there may be extraarticular causes of impingement. Together with the increased diagnosis of impingement, arthroscopic treatment is increasingly frequent and has become the standard treatment. This report analyzes a case of extraarticular hip impingement caused by contact between the femur and a prominent anteroinferior iliac spine (AIIS), probably due to a healed old avulsion and its later arthroscopic management. PMID- 26999927 TI - [Resection of an aneurysmal bone cyst in the proximal humerus with a non vascularized fibular graft. Case report]. AB - An aneurysmal bone cyst is a benign lesion involving the marrow of long bones; it accounts for 6% of primary bone lesions and may occur as a secondary lesion with other benign or malignant bone tumors. We describe herein the case of a seven year-old female with an aneurysmal bone cyst which was diagnosed clinically, radiographically and with a CAT scan, and confirmed with histopathology. Resection was performed using the eggshell technique and a non-vascularized left fibular bone graft. The patient did well up to the fourth postoperative year, which is consistent with what has been reported in world literature. PMID- 26999928 TI - [Reverse shoulder prosthesis]. PMID- 26999929 TI - [Diagnosis of sphincter of Oddi dysfunction in patients with postcholecystectomy syndrome from hepatobiliary scintigraphic findings]. AB - OBJECTIVE: to diagnose and estimate the clinical value of postcholecystectomy sphincter of Oddi dysfunction in patients. MATERIAL AND METHODS: Examinations were made in 100 postcholecystectomy patients without signs of cholestasis; of them 14 postpapillotomy patients formed a comparison group. Hepatobiliary scintigraphy using the radiotracer 99mTC-bromeside was performed for 90 minutes with cholagogue breakfast at 45 minutes. Common bile duct and duodenal functions and duodenogastric reflux (DGR) were evaluated comparing them with clinical, laboratory, and instrumental findings. RESULTS: Two patient groups were identified according to bile outflow changes. In Group I consisting of 20 (23.2%) patients, the time of maximum accumulation (Tmax) of the radiopharmaceutical in the projection of the choledochus coincided with that in the cholagogue test (46.0 1.8 min) and in Group 2 including 66 (76.8%) patients that was shorter than in the cholagogue test (32.9 +/- 6.8 min) (p<0.05). In Group 2, Tmax was similar to that in the comparison group (30.9 +/- 7.5 min; p > 0.05) and there was no significant difference in intestinal imaging time (18.6 +/- 6.0 min versus 17.6 +/- 0.8) either, which could be indicative of sphincter of Oddi dysfunction. Diarrhea was observed in 73% of the patients with sphincter of Oddi dysfunction and in 86% of the patients in the comparison group versus 10% of the patients with normal bile passage (p<0.01). Statistical data processing showed a correlation of the indicators of sphincter of Oddi dysfunction with those of duodenal evacuator function (r = 0.57; p < 0.0005) and DGR (r = 0.74; p < 0.009). CONCLUSION: Postcholecystectomy sphincter of Oddi dysfunction assumes the greatest clinical value in patients with duodenal motor-evacuator dysfunction, which should be hepatobiliamy scintigraphic, kept in mind when choossphincter of Oddi dysfunction ing a treatment policy. PMID- 26999930 TI - [Quantitative analysis of diffusion-weighted magnetic resonance images during chemoradiation therapy for cancer of the cervix uteri: Prognostic role of pretreatment diffusion coefficient values]. AB - OBJECTIVE: to carry out a quantitative analysis of diffusion-weighted magnetic resonance images (DWI) in cancer of the cervix uteri (CCU) and to estimate the possibility of using pretreatment measured diffusion coefficient (MDC) to predict chemoradiation therapy (CRT). MATERIAL AND METHODS: The investigation prospectively enrolled 46 women with morphologically verified Stages IB-IVB CCU. All the women underwent diffusion-weighted magnetic resonance imaging of pelvic organs before and after treatment. A semiautomatic method was used to determine tumor signal intensity (SI) on DWI at b 1000 s/mm2 (SI b1000) and tumor MDC. The reproducibility of MDC measurements was assessed in 16 randomly selected women. The investigators compared the pretreatment quantitative DWI measures in complete and incomplete regression (CR and IR) groups and the presence and absence of tumor progression during a follow-up. An association of MDC with progression-free and overall survivals (PFS and OS) was determined in the patients. RESULTS: A semiautomatic tumor segmentation framework could determine the pretreatment quantitative DMI measures with minimal time spent and high reproducibility. The mean tumor MDC was 0.82 +/- 0.14 x 10(-3) mm2/s. CR and IR were established in 28 and 18 women, respectively. The MDC < or = 0.83 x 10(-3) mm2/s predicted CR with a sensitivity of 64.3% and a specificity of 77.8% (p=0.007). The median follow-up was 47 months (range, 3-82 months). With the MDC < or = 0.86 x 10(-3) mm2/s, 5 year PFS was 74.1% versus 42.1% with a higher MDC (p=0.023) and 5-year OS was 70.4 and 40.6%, respectively (p=0.021). The survival difference was insignificant in relation to the degree of tumor regression. The pretreatment IS at b1000 was of no prognostic value. CONCLUSION: The pretreatment tumor MDC may serve as a biomarker for predicting the efficiency of CRT for CCU. PMID- 26999931 TI - [Possibilities of a software-based hybrid single photon emission computed tomography/magnetic resonance imaging in the diagnosis of complicated diabetic foot syndrome]. AB - OBJECTIVE: To give the results of a software-based hybrid single photon emission computed tomography/magnetic resonance imaging (SPECT/MRI) in detecting osteomyelitis (OM) in patients with diabetic foot syndrome (DFS). MATERIAL AND METHODS: Seventy-six patients (35 men and 41 women) (mean age, 59.4 +/- 7.1 years) with type 1 and 2 diabetes mellitus and suspected OM were examined. The investigation enrolled patients with neuropathic (n = 25), ischemic (n = 13), and mixed (n = 38) DFS. All the patients underwent (99m)Tc-HMPAO/ (99m)Tc-technefit labeled leukocyte scintigraphy; magnetic resonance imaging was performed in 30 patients. The results were combined using RView 9.06 software (Colin Studholme). RESULTS: Labeled leukocyte SPECT to Diagnose OM yielded 255 true positive (TP), 38 true negative (TN), 12 false negative (FP), and 1 false negative (FN) results. The accuracy of the technique was 82.9%. The FP results were due to the low resolution of the technique and to the small sizes of the object under study. One FN result was detected in a patient with ischemic DFS because of reduced blood flow. MRI to identify OM in patients with DFS provided 20 TP, 16 TN, 4 FP, and 2 FN results. Its diagnostic accuracy was 85.7%. The relative low specificity of MRI was associated with the presence of FP results due to the complexity of differential diagnosis of bone marrow edema and inflammatory infiltration. Assessing 42 hybrid SPECT/MR-images revealed 21 TP, 17 TN, 3 FP, and I FN results. The diagnostic accuracy was equal to 95.9%. CONCLUSION: Thus, comparing MRI (90.9% sensitivity and 80.0% specificity), labeled leukocyte scintigraphy (96.2% sensitivity and 76.0% specificity), and hybrid SPECT/MRI (95.5% sensitivity and 85.0% specificity) showed the high diagnostic efficiency of the latter. PMID- 26999932 TI - [Some patterns of development of radio-induced metachronous tumors]. AB - OBJECTIVE: to determine the specific features of the development of metachronous tumors and survival rates in patients with metachronous primary and multiple cancers after radiotherapy for the first tumor. MATERIAL AND METHODS: The archival data of the Chelyabinsk Regional Oncology Dispensary on the treatment of 232 patients, in whom metachronous primary and multiple tumors occurred after radiotherapy for primary tumor, were studied. RESULTS: The patients' mean age at the diagnosis of the first tumor was 60.23 years (95% CI 58.75-61.72). The time'from the first tumor to the second one averaged 91.81 months (95% CI 80.57 103.05). The patients survived for an average of 129.41 months (95% CI 116.55 142.28) after the diagnosis of the first tumor and 37.64 months (95% CI 31.92 43.35) after the occurrence of the second tumor. Overall, the patients survived for an average of 127.03 months (95% CI 114.02-140.03) following radiotherapy for the first tumor. According to the classification, the authors identified three metachronous tumor subgroups: multicentric multiple tumors in one organ (16.0%), systemic tumors and tumors of paired organs (15.5%), and nonsystemic multiple tumors of different organs (68.5%). CONCLUSION: Patients with multicentric metachronous multiple tumors in one organ are younger and have the shortest time from the diagnosis of the first tumor to the emergence of the second one and the longest survival after the diagnosis of the first tumor, that after the detection of the second tumor and that after the initiation of radiotherapy. Patients with non-systemic multiple tumors in different organs are nlder and have the longest time from the diagonosis of the first tumor to Ine occurrence of the semetnd one and the shortest survival. PMID- 26999933 TI - [Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors]. AB - Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency. PMID- 26999934 TI - [Multiparameter magnetic resonance imaging in the diagnosis of cancer of the cervix uteri]. AB - Cancer of the cervix uteri (CCU) ranks third in the incidence of malignancies in women. The choice of CCU treatment mainly depends on the extent of the tumor process, i.e., the stage of the disease. Determining the stage of CCU is based on the clinical classification of the International Federation of Gynecology and Obstetrics (FIGO) (2009) and has a number of substantial limitations in evaluating parametrial invasion, tumor spread to the pelvic wall, and involvement of regional lymph nodes and in determining the true tumor sizes. Magnetic resonance imaging (MRI) is now the method of choice in staging invasive CCU. Multiparameter MRI will be able to enhance the efficiency of diagnosing microinvasive CCU as well (FIGO 2009), to plan surgical and/or chemoradiation treatment, to evaluate its efficiency, and to diagnose locally recurrent CCU. PMID- 26999936 TI - [In memory of Professor Igor' Petrovich Korolyuk]. PMID- 26999935 TI - [Radiology in the Russian Federation in 2014]. PMID- 26999937 TI - Evaluation of white-to-white distance and anterior chamber depth measurements using the IOL Master, slit-lamp adapted optical coherence tomography and digital photographs in phakic eyes. AB - INTRODUCTION: The accurate measurement of the anterior chamber internal diameter and depth is important in ophthalmic diagnosis and before some eye surgery procedures. The purpose of the study was to compare the white-to-white distance measurements performed using the IOL-Master and photography with internal anterior chamber diameter determined using slit lamp adapted optical coherence tomography in healthy eyes, and to compare anterior chamber depth measurements by IOL-Master and slit lamp adapted optical coherence tomography. MATERIAL AND METHODS: The data were gathered prospectively from a non-randomized consecutive series of patients. The examined group consisted of 46 eyes of 39 patients. White to-white was measured using IOL-Master and photographs of the eye were taken with a digital camera. Internal anterior chamber diameter was measured with slit-lamp adapted optical coherence tomography. Anterior chamber depth was measured using the IOL Master and slit-lamp adapted optical coherence tomography. Statistical analysis was performed using parametric tests. A Bland-Altman plot was drawn. RESULTS: White-to-white distance by the IOL Master was 11.8 +/- 0.40 mm, on photographs it was 11.29 +/- 0.58 mm and internal anterior chamber diameter by slit-lamp adapted optical coherence tomography was 11.34?0.54 mm. A significant difference was found between IOL-Master and slit-lamp adapted optical coherence tomography (p<0.01), as well as between IOL Master and digital photographs (p<0.01). There was no difference between SL-OCT and digital photographs (p>0.05). All measurements were correlated (Spearman p<0.001). Mean anterior chamber depth determined using the IOL-Master was 2.99 +/- 0.50 mm and by slit lamp adapted optical coherence tomography was 2.56 +/- 0.46 mm. The difference was statistically significant (p<0.001). The correlation between the values was also statistically significant (Spearman, p<0.001). CONCLUSIONS: Automated measurements using IOL-Master yield constantly higher values than measurements based on direct eye visualization slit-lamp adapted optical coherence tomography and digital photographs. In order to obtain accurate measurements of the internal anterior chamber diameter and anterior chamber depth, a method involving direct visualization of intraocular structures should be used. PMID- 26999938 TI - [Utility of optical coherence tomography in assessing macular anatomy after conventional surgical repair of rhegmatogenous retinal detachment]. AB - AIM: To determine the utility of optical coherence tomography in assessing macular anatomy of patients treated with conventional surgery for rhegmatogenous retinal detachment involving the macula. MATERIAL AND METHODS: 42 patients (42 eyes) treated for rhegmatogenous retinal detachment with macular involvement were enrolled in the study. 14 of them were treated with segmental scleral buckling, 8 patients--with encircling scleral buckling, and 20 others--with scleral explant placed along the horizontal or vertical meridian and encircling scleral band. The assessment in each case involved the assessment of best corrected visual acuity, Amsler grid test and optical coherence tomography of the macular region performed on day 1. following surgery as well as in months 1, 3 and 6 afterwards. RESULTS: On day 1. after the surgery, residual retinal detachment with macular involvement was confirmed in all patients with optical coherence tomography and no best corrected visual acuity improvement was noted. The central retinal elevation ranged from 315 microm to 480 microm (mean 387 microm). Subsequent follow-up assessments performed at months 1, 3 and 6 showed a gradual reabsorption of subretinal fluid and the reduction of central retinal elevation to 371 pm, 286 microm and 219 microm, respectively. At the final follow-up, the submacular fluid was completely resolved in 88.1% of eyes. The statistical analysis showed a significant correlation between the reduction of central retinal elevation and best corrected visual acuity improvement (p<0.01). CONCLUSIONS: Our results show that the optical coherence tomography may be a useful tool in assessing the residual retinal detachment responsible for the lack of visual acuity improvement after the uneventful conventional retinal detachment surgery. PMID- 26999939 TI - [Managment of subretinal heamorrhages within the macular area using intravitreal injections of recombined tissue plasminogen activator, sulphur hexafluoride and ranihizumab--preliminary report]. AB - Submacular hemorrhages cause serious vision impairment. Patient observation, waiting for the spontaneous blood reabsorption and resolution of the haemorrhage leads to the severe damage to retinal tissue as a result of scar formation. The paper presents 7 cases of patients with submacular haemorrhages treated with intravitreal injections of recombined tissue plasminogen activator (rtPA) and sulphur hexafluoride (SFG). In 4 cases, the haemorrhage was secondary to AMD, in two cases to trauma, and it was idiopathic in one case. All patients were treated with intravitreal injections of rtPA and SF6 for thrombolysis and pneumatic displacement of haemorrhage outside macular structures. Ranibizumab was additionally administered to patients with age-related macular degeneration. Such treatment improved visual acuity in all patients, reducing the central retinal thickness as shown in follow-up optical coherence tomography. The presented treatment of submacular hemorrhages with intravitreal injections of rtPA and SF6 provided good results, but in order to develop a standard management algorithm for this disease, the analysis of larger patient sample is required. PMID- 26999940 TI - [Risk factors for the recurrence of choroidal melanoma after the Ru-106 brachytherapy]. AB - PURPOSE: The aim of the study was to determine factors, which are likely to affect local recurrence of choroidal melanoma after ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy. MATERIAL AND METHODS: We analysed 355 cases of patients with choroidal melanoma treated ruthenium-106 brachytherapy with or without adjunctive transpupillary thermotherapy. These were divided into two groups of patients with confirmed recurrence of choroidal melanoma (97 subjects) and patients without recurrence (control group, 258 subjects). RESULTS: We found a significant relationship between tumour recurrence and the presence of retinal detachment at the time of diagnosis, tumor shape, its large size and location with the marginal adjacency to the optic disc and with the anterior margin located 1-2 optic disc diameters from the macula. Among other risk factors, the use of COB plaque with supplementary transpupillary thermotherapy, dose to the tumor base, visibility of tumor base shade during transillumination, and uncertainty regarding precise plaque placement showed a significant correlation with tumour recurrence, just as the presence of metastases did. CONCLUSION: It seems that large tumour size and its location at the proximity of the optic disc are the key factors to affect the failure of brachytherapy and recurrence in patients with choroidal melanoma. PMID- 26999941 TI - [Bilateral abnormalities in central serous chorioretinopathy seen in optical coherence tomography, ultra-widefield fluorescein angiography and microperimetry- case report]. AB - Central serous chorioretinopathy is a common retinopathy, which is manifested by the idiopathic detachment of the neurosensory retina in the posterior pole, secondary to fluid leakage from choroidal vessels at the level of retinal pigment epithelium. The disease is typically unilateral and affects young men. We present a case of a 48-year old man, admitted to the Department of Vitreo-Retinal Surgery, Medical University in Lublin, reporting vision impairment in his right eye. The bilateral ocular exam followed by optical coherence tomography, ultra widefield fluorescein angiography and microperimetry revealed bilateral central serous chorioretinopathy. This case presents a bilateral manifestation of central serous chorioretinopathy and emphasizes the role of advanced diagnostic imaging techniques in analyzing retinal function and disease management. PMID- 26999942 TI - [Bilateral exudative retinal detachment as the first sign of breast cancer--case report]. AB - Metastatic choroidal tumours are the most common type of intraocular neoplasms in adults. Currently choroidal metastases are being diagnosed more frequently, generally due to the higher incidence of carcinomas, longer survival of cancer patients and better diagnostic possibilities. The most common primary cancers locations are breasts in women and lungs in men. These tumours are usually symptomatic and only in very rare cases metastases are the first symptom of carcinoma. We present such an atypical case of a 53-year-old female patient with bilateral exudative retinal detachment, which was the first symptom of a generalized malignancy originating in the mammary gland. Primary tumours and metastatic lesions both require a meticulous interdisciplinary examination, as well as the interdisciplinary treatment. Close liaison between oncologists and other specialists can result in faster diagnosis and improve treatment outcomes. Moreover, public health programs aimed at early detection of the most common tumours may help achieve better treatment results. PMID- 26999943 TI - [Atypical case of acute retinal necrosis secondary to the primary herpes simplex infection]. AB - Acute retinal necrosis is a rare manifestation of viral chorioretinitis, accompanied by occlusive vasculitis, which is associated with poor visual prognosis. The main causal factors include varicella-zoster virus in older patients and herpes simplex in younger ones. The disease typically manifests as a reactivation of latent infections. We present a case of a 57-year-old female with atypical clinical manifestation of acute retinal necrosis secondary to the primary viral infection with herpes simplex. The serology panel of vitreous tap and blood sample confirmed viral aetiology (H. simplex). The initial clinical signs included optic disc edema with retinitis presenting as self-limiting, slowly progressing, peripheral lesions, later followed by uveitis. The antiviral therapy resolved the symptoms of uveitis and enabled healing of retinal lesions, however the natural course of disease was later complicated with retinal detachment. It was successfully treated with vitreoretinal surgery. Despite aggressive treatment, the final visual outcome was unfavourable, due to optic nerve atrophy. PMID- 26999944 TI - [The use of aflibercept (Eylea) in the treatment of polypoidal choroidal vasculopathy--case report]. AB - The paper presents a case of a 25-year-old woman referred to the Outpatient Clinic at the Department of Ophthalmology, University Clinical Centre in Gdansk, with sudden vision impairment in her right eye. Clinical manifestation and diagnostic tests gave a basis for the preliminary diagnosis of polypoidal choroidal vasculopathy. Polypoidal choroidal vasculopathy is a type of choroidal neovascularisation, frequently confused with age-related macular degeneration. Standard treatment includes photodynamic therapy and intravitreal injections of anti-vascular endothelial growth factor agents. 2.0 miligrams of aflibercept was administered as an intravitreal injection, causing a rapid, significant improvement of visual function and proper anatomical relationships within the retina. PMID- 26999945 TI - [Sclerotherapy of ocular venous malformation in small child--case report]. AB - We present a case of a 4-year-old girl with ocular venous malformation in her left eye. Over a one-year follow up, the symptoms progressed and sclerotherapy with bleomycin was performed. The bleomycin solution was injected directly into the abnormal vessel under visual control, which lead to a complete obliteration of malformation in a long-term follow-up. PMID- 26999947 TI - [Fuchs endothelial corneal dystrophy and trinucleotide repeat expansion in TCF4- implications for diagnostics and therapy]. AB - Fuchs endothelial corneal dystrophy is the most common genetically determined degenerative disease of the cornea. In Polish patients the dystrophy is a leading indication for lamellar posterior keratoplasty. The genetic background of Fuchs endothelial corneal dystrophy is complex and heterogeneous. A number of TCF4 gene variants have been strongly associated with the development of this disorder with the most important of them being the trinucleotide repeat expansion CTG18.1. The aim of the study is to present this novel and extraordinarily strong genetic association with Fuchs endothelial corneal dystrophy. Studies on the impact of CTG18.1 on corneal endothelial cells may help to explain the molecular mechanism involved in the pathogenesis of the corneal dystrophy. This could significantly improve diagnostics and therapy of Fuchs endothelial corneal dystrophy patients. PMID- 26999946 TI - [The utility of selected ocular examinations in individuals with systemic lupus erythematosus]. AB - Systemic lupus erythematosus belongs to the group of autoimmune diseases, in which the accumulation of antigen-antibody complexes may lead to multiple organ failure. Ocular manifestation of the disease is also possible. Ocular changes are attributable to either the disease itself or to the complications associated with administered therapies. The aim of this research was to present the utility of ophthalmic and diagnostic devices in interpreting ocular changes in patients with systemic lupus erythematosus. Ultrasound biomicroscopy and spectral domain optical coherence tomography provide the insight into the anterior segment morphology with special emphasis on the cornea and iridocorneal angle in patients with Systemic Lupus Erythematosus. Confocal microscopy presents particular corneal layers in vivo what enables detecting the location of inflammatory and chloroquine deposits. Ocular Response Analyzer estimates changes in corneal hysteresis and resistance parameters in patients with systemic lupus erythematosus. The optical coherence tomography of the macula and multifocal electroretinography enable detecting subclinical forms of maculopathy. Evaluation of arterial flow parameters and characteristics in ocular circulation measured during fluorescein angiography and colour Doppler imaging quantifies functional and morphological changes in ocular circulation. The appropriate use of diagnostic devices along with accurate interpretation of findings may be crucial for early detection of ocular changes in many diseases with ocular involvement, including systemic lupus erythematosus. PMID- 26999949 TI - [37th Meeting of the European Strabismological Association, Venice, Italy, October 1-4, 2015: Report]. PMID- 26999950 TI - [Izabela Kozuchowska-Zachajkiewicz (1923-2015) -- ophthalmology professor]. PMID- 26999951 TI - Significance of Meningococcal Hyperinvasive Clonal Complexes and their Influence on Vaccines Development. AB - Neisseria meningitidis is a commensal of human nasopharynx and humans are the only known reservoir and host of this bacterium. It is also known as a dangerous and devastating pathogen, and infection with N. meningitidis may lead to rapidly progressing septicemia or meningitis. These severe infections, called invasive meningococcal disease (IMD), are one of the major public health threats worldwide. IMD may occur sporadically, but also in outbreaks, epidemics, and pandemics. Most of the IMD cases in the world are caused by isolates of genetically related groups, clonal complexes (CC), including those with special epidemiological significance called hyperinvasive clonal complexes. It is still unknown why some of them may persist for decades, whereas other are quickly replaced and disappear. As a consequence, the epidemiological situation of IMD is variable worldwide and greatly depends on the emergence and widespread of clones belonging to hyperinvasive clonal complexes. Their occurrence has serious implications for health policy, requiring often mass immunization campaigns. Paradoxically, alarming situations caused by hyperinvasive CCs stimulated the development and introduction of new vaccines against meningococci. Despite the unquestionable success of these vaccines, isolates of hyperinvasive clones constitute a permanent public health threat, because they are constantly circulating and able to modify their antigenic profiles to escape the host immune response. Therefore, continuous monitoring of meningococcal isolates including thorough molecular typing is indispensable and fundamental for taking appropriate preventive measures. PMID- 26999952 TI - Prevalence of Polyoma BK Virus (BKPyV), Epstein-Barr Virus (EBV) and Human Papilloma Virus (HPV) in Oropharyngeal Cancer. AB - The aim of this study was to analyze the prevalence of BK virus, Human Papillomavirus and Epstein-Barr virus in oropharyngeal cancer, and to test our hypothesis that BKV/HPV/EBV co-infection plays a role in oropharyngeal squamous cell carcinoma. The correlation between viral infection, OSCC, anatomic location, pre-treatment staging, evidence of metastases to lymph nodes, and grading was also investigated. The examination samples were collected from 62 patients from paraffin tissue blocks. Males (90.3%) with, smoking (83.9%) and alcohol abuse (67.7%) problems prevailed in the studied group. G2 histological type was recognized in 80.6% cases. T4 (77.4%) and N2 (56.5%) traits occurred in the majority of patients. No cases of metastasis were observed (M0 100%). HPV - 24.2%, EBV - 27.4% and BKV 17.7% were detected in the studied samples. We observed co-infection EBV/BKV in 8% of cases, HPV/BKV in 4.8%, and HPV/EBV in 9% cases. Only in two cases co-infection of all three viruses was found. PMID- 26999954 TI - Isolation and Characterization of Streptomycetes with-Plant Growth Promoting Potential from Mangrove Ecosystem. AB - A total of 66 actinomycetes isolates were isolated from mangroves of Andhra Pradesh, India, using various enrichment techniques and pretreatments. The samples were collected from Coringa mangrove ecosystem and pre-treated by enrichment with CaCO3, sodium dodecyl sulphate and phenol, plated on the media supplemented with cycloheximide (50 mg/ml), nystatin (25 mg/ml) and nalidixic acid (50 mg/ml). The population count of actinomycetes fluctuated from 1.9 x 10(5) to 8.0 x 10(5)/g soil. Out of the isolated 66 actinomycetes, 8 isolates possessing plant growth promoting potential were further studied and characterized by physiological and biochemical traits and identified by 16S rRNA gene sequencing as different species of Streptomycetes genera. PMID- 26999953 TI - Biodecolorization and Bioremediation of Denim Industrial Wastewater by Adapted Bacterial Consortium Immobilized on Inert Polyurethane Foam (PUF) Matrix: A First Approach with Biobarrier Model. AB - The present experiments were studied on bioremediation of denim industry wastewater by using polyurethane foam (PU foam) immobilized bacterial cells. About 30 indigenous adapted bacterial strains were isolated from denim textile effluent out of which only four isolates were found to be efficient against crude indigo carmine degradation using broth decolorization method. The selected bacterial strains were identified as Actinomyces sp., (PK07), Pseudomonas sp., (PK18), Stenotrophomonas sp., (PK23) and Staphylococcus sp., (PK28) based on microscopic and biochemical characteristics. The bacterial immobilized cells have the highest number of viable cells (PK07, PK18, PK23 and PK28 appeared to be 1 x 10(8), 1 x 10(9), 1 x 10(6) and 1 x 10(7) CFU/ml respectively) and maximum attachment efficiency of 92% on PU foam. The complete degradation using a consortium of PU foam immobilized cells was achieved at pH 6, 27 degrees C, 100% of substrate concentration and allowed to develop biofilm for one day (1.5% W/V). In SEM analysis, it was found that immobilization of bacterial cells using PUF stably maintained the production of various extracellular enzymes at levels higher than achieved with suspended forms. Finally, isatin and anthranilic acid were found to be degradation products by NMR and TLC. The decolorized dye was not toxic to monkey kidney cell (HBL 100) at a concentration of 50 MUl and 95% of cell viability was retained. A mathematical model that describes bacterial transport with biodegradation involves a set of coupled reaction equations with non-standard numerical approach based on the time step scheme. PMID- 26999955 TI - Germination and Inactivation of Alicyclobacillus acidoterrestris Spores Induced by Moderate Hydrostatic Pressure. AB - Given the importance of spoilage caused by Alicyclobacillus acidoterrestris for the fruit juice industry, the objective of this work was to study the germination and inactivation of A. acidoterrestris spores induced by moderate hydrostatic pressure. Hydrostatic pressure treatment can induce the germination and inactivation of A. acidoterrestris spores. At low pH, spore germination of up to 3.59-3.75 log and inactivation of 1.85-2.04 log was observed in a low pressure window (200-300 MPa) applied at 50 degrees C for 20 min. Neutral pH suppressed inactivation, the number of spores inactivated at pH 7.0 was only 0.24-1.06 log. The pressurization temperature significantly affected spore germination and inactivation. The degree of germination in apple juice after pressurization for 30 min with 200 MPa at 20 degrees C was 2.04 log, with only 0.61 log of spores being inactivated, while at 70 degrees C spore germination was 5.94 log and inactivation 4.72 log. This temperature strongly stimulated germination and inactivation under higher (500 MPa) than lower (200 MPa) pressure. When the oscillatory mode was used, the degree of germination and inactivation was slightly higher than at continuous mode. The degree of germination and inactivation was inversely proportional to the soluble solids content and was lowest in concentrated apple juice. PMID- 26999956 TI - Autochthonous Gut Bacteria in Two Indian Air-breathing Fish, Climbing Perch (Anabas testudineus) and Walking Catfish (Clarias batrachus): Mode of Association, Identification and Enzyme Producing Ability. AB - Scanning electron microscopy (SEM) was used to define the location of epithelium associated bacteria in the gastrointestinal (GI) tract of two Indian air breathing fish, the climbing perch (Anabas testudineus) and walking catfish (Clarias batrachus). The SEM examination revealed substantial numbers of rod shaped bacterial cells associated with the microvillus brush borders of enterocytes in proximal (PI) and distal regions (DI) of the GI tract of both the fish species. Ten (two each from the PI and DI of climbing perch and three each from the PI and DI of walking catfish) isolated bacterial strains were evaluated for extracellular protease, amylase and cellulase production quantitatively. All the bacterial strains exhibited high cellulolytic activity compared to amylolytic and proteolytic activites. Only two strains, CBH6 and CBH7, isolated from the DI of walking catfish exhibited high proteolytic activity. Maximum cellulase activity was exhibited by the strain, CBF2, isolated from the PI of climbing perch. Six most promising enzyme-producing adherent bacterial strains were identified by 16S rDNA gene sequence analysis. The strain ATH1 (isolated from climbing perch) showed high similarity fo Bacillus amyloliquefaciens whereas, the remaining five strains (isolated from walking catfish) were most closely related to Bacillus licheniformis. PMID- 26999957 TI - Physiology and Molecular Phylogeny of Bacteria Isolated from Alkaline Distillery Lime. AB - This paper presents the results of the research on the number, taxonomic composition, and biochemical properties of bacterial strains isolated from the alkaline Solvay distillery lime, deposited at the repository in Janikowo (central Poland). Fifteen strains out of 17 were facultative alkaliphiles and moderate halophiles, and two were alkalitolerants and moderate halophiles. The number of aerobic bacteria cultured in alkaline lime was approximately 10(5) CFU ml(-1), and the total number of bacteria was 10(7) cells g(-1). According to 16S rRNA gene sequence analysis, nine strains belonged to the genus Bacillus, six to the genus Halomonas, one to the genus Planococcus, and one to the genus Microcella. Strains that hydrolyse starch and protein were the most numerous. Esterase (C4) and esterase lipase (C8) were detected in the majority of bacterial strains. Twelve strains exhibited alpha-glucosidase activity and nine, naphtol-AS-BI phosphohydrolase activity. The present study proves that alkaliphilic bacteria of this type may constitute a source of potentially useful extremozymes. PMID- 26999958 TI - Inhibitory Effect of Newly-Synthesized Chalcones on Hemolytic Activity of Methicillin-Resistant Staphylococcus aureus. AB - Pathogenicity of methicillin-resistant Staphylococcus aureus (MRSA) is associated with a broad spectrum of virulence factors, amongst which is alpha-hemolysin. The aim of this study was to investigate the effect of three newly-synthesized chalcones (1,3- Bis-(2-hydroxy-phenyl)-propenone, 3-(3-Hydroxy-phenyl)-1-(2 hydroxy-phenyl)-propenone and 3-(4-Hydroxy-phenyl)-1-(2-hydroxy-phenyl) propenone) on a-hemolysin production of clinical isolates of MRSA. Subinhibitory concentrations of the tested compounds reduced hemolytic activity of MRSA strains, with almost complete abolishment of hemolysis at concentrations in the range of 1/2-1/4 x MIC (25-12.5 MUg/ml). In conclusion, newly-synthesized chalcones tested in this study showed potent inhibitory activity on alpha hemolysin production of multiresistant and genetically diverse MRSA strains. PMID- 26999959 TI - Molecular Methods for Identification of Monophasic Salmonella Typhimurium Strains. AB - Two molecular biology methods were used to differentiate Salmonella enterica 1,4,[5],12:i:- strains: "Salmonella Check&Trace microarray" (CT) and multiplex PCR (mPCR). For 92 strains in CT result "Salmonella 1,4,[5],12:i:-" were obtained. Those strains were confirmed in mPCR as monophasic fljB-lack Salmonella Typhimurium. For 17 strains, which in CT assay were recognized as Salmonella Typhimurium, the same identification was obtained in mPCR. Reference Salmonella strains: Lagos, Agama, Tsevie, Glocester and Tumodi in CT were recognized as Salmonella genovar, in mPCR--as Salmonella O:4, H:i other than Salmonella Typhimurium, the same like Salmonella Farsta, recognized incorrectly in CT as Salmonella Typhimurium. PMID- 26999960 TI - Probable Interspecies Transfer of the bla(VIM-4) Gene between Enterobacter cloacae and Klebsiella pneumoniae in a Single Infant Patient. AB - We report the interspecies transfer of the bla(VLM-4) gene in MBL-producing Enterobacter cloacae and Klebsiella pneumoniae isolates from a newborn patient who had received meropenem therapy. We show evidence that gene bla(VIM-4) was transmitted as a part of the class-1 integron on a ca. -90 kb conjugative plasmid. High homology of nucleotide sequence was observed between the integron found in VIM-4 producing E. cloacae and K. pneumoniae strains tested and class-1 integrons previously reporteded in Pseudomonas aeruginosa from Hungary and Poland. This finding may suggest P. aeruginosa as a potential source of acquired VIM-4 in Enterobacteriaceae. PMID- 26999961 TI - Five Years' Evaluation of the BD ProbeTec System for the Direct Molecular Detection of Mycobacterium tuberculosis Complex in Respiratory and Nonrespiratory Clinical Samples. AB - In this study, Mycobacterium tuberculosis complex was detected by BD ProbeTec ET system in 4716 respiratory and 167 nonrespiratory samples [mostly (98%) smear negative). Sensitivity, specificity, positive and negative predictive values were 81.8%, 98.3, 85.1 and 97.9 for respiratory and 100%, 96.2, 64.7 and 100, for nonrespiratory samples, respectively. Among 149 (3.1%) ProbeTec DTB positive and culture negative samples, 72 (65 respiratory and seven nonrespiratory) (48.3%) were recovered from the patients who were evaluated as having TB infection. The system has been found as useful in early diagnosis of tuberculosis infection in association with the clinical, radiological and histopathological findings. PMID- 26999962 TI - Tuberculosis in Antelopes in a Zoo in Poland--Problem of Public Health. AB - Bovine tuberculosis is an infectious disease that occurs in many species of both domestic and wild animals, as well as those held in captivity. The etiological factor is the acid resistant bacillus (Mycobacterium bovis or Mycobacterium caprae), which is characterized by the major pathogenicity among mycobacteria belonging to the Mycobacterium tuberculosis complex. The material from 8 antelopes from the zoo, suspected for tuberculosis were examined, and M. bovis strains were isolated from 6 of them. The spoligotyping method showing spoligo pattern 676763777777600. In Poland, this spoligotype has not been observed so far. PMID- 26999964 TI - [One more step]. PMID- 26999963 TI - Drug Resistance and Population Structure of Mycobacterium tuberculosis Beijing Strains Isolated in Poland. AB - In total, 1095 Mycobacterium tuberculosis clinical isolates from 282 patients with drug-resistant and 813 with drug-sensitive tuberculosis (TB) in Poland during 2007-2011 were analysed. Seventy-one (6.5%) patients were found to have strains of Beijing genotype as defined by spoligotyping. The majority of patients were Polish-born; among foreign-born a large proportion came from Chechnya and Vietnam. Analysis showed strong associations between Beijing genotype infection and MDR, pre-XDR and XDR resistance, with a considerable relative risk among new patients, suggesting that this is due to increased spread of drug-resistant strains rather than acquisition of resistance during treatment. PMID- 26999965 TI - [Hemiarthroplasty of the radial head in patients with Mason Johnston types III and IV fracture]. AB - INTRODUCTION: The radial head is a primary and important stabilizer of the elbow, mainly for valgus stability, posterolateral and axial displacement of the radius and varus loading. Radial head fractures account for 1.7-5% of all fractures in adults, 17-19% of elbow trauma, and 33% of all elbow fractures. The latter is the most common one at this level. The alternatives for a radial head fracture that cannot be reconstructed include excision of the radial head or hemiarthroplasty. OBJECTIVE: To assess the function of patients who underwent radial head hemiarthroplasty for Mason-Johnston types III and IV fractures, us- ing the Mayo Elbow Performance Index (MEPI) and Quick-Dash (QD). MATERIAL AND METHODS: A one year long observational, cross-sectional and ambispective study was conducted at the Thoracic Limb Service, "Lomas Verdes" Orthopedics and Traumatology Hospital. The patients included were ages 18 to 60 years, had a diagnosis of Mason-Johnston types III and IV radial head fractures and were treated with radial head hemiarthroplasty. RESULTS: A total of seven patients were included, 3 females (42.9%) and 4 males (57.1%). The results of elbow function according to the MEPI were as follows: Excellent, 6 patients (85.7%); Good, one patient (14.3%). The results of the QD functionality and symptoms scale were: 6 patients had a score of 0-5, and one patient more than 10. CONCLUSIONS: Surgical treatment consisting of radial head hemiarthroplasty for Mason-Johnston types III and IV fractures yields good short-term results, because it provides excellent to good function, valgus and varus elbow stability, and minimum elbow symptoms. PMID- 26999966 TI - [Treatment of elbow epicondylitis with platelet rich plasma versus local corticosteroids]. AB - BACKGROUND: Epicondylitis is a highly frequent condition in the Mexican population. Recent studies have reported good results with platelet rich plasma. However, corticosteroids are the most common treatment used in Mexico. OBJECTIVE: To conduct a comparative study to determine which treatment provides better results (platelet rich plasma versus corticosteroids). MATERIAL AND METHODS: Patients were randomized into two groups. Group A was treated with a single administration of platelet rich plasma and group B with a single dose of 40 mg of methylprednisolone. Patients were assessed using a visual analog scale (VAS) and the Quick DASH scale, applied before the procedure, and at one, three and six months. RESULTS: The results were compared with an analysis using the Student t test. One month after treatment the patients had improvement with no significant difference between both groups. At three months results were better with platelet rich plasma; however, at six months improvement with the latter declined slightly. CONCLUSIONS: The results show that platelet rich plasma provided better results from the perspective of pain control and effect duration. However, the number of applications and the possibility of improving the outcomes if combined with rehabilitation have not yet been determined. PMID- 26999967 TI - [Clinical and radiological results of fractures of the proximal humerus treated with intramedullary nailing and possible risk factors of a poor outcome]. AB - BACKGROUND: To assess the clinical and radiological results of fractures of the proximal humerus treated with intramedullary nail fixation as well as the risk factors associated with a poor outcome. METHODS: Patients were analyzed retrospectively with a minimum follow-up of one year. An objective clinical assessment was made using the Constant scale, the subjective satisfaction scale, VAS, and the DASH scale to measure disability. The radiological assessment included AP and axial X-rays in the scapular plane. RESULTS: Forty-six patients were enrolled. The clinical assessment showed that 91.3% of them were satisfied with treatment. Mean mobility was 1550 of flexion, 600 of lateral and medial rotation. The mean Constant score was 70 and the DASH score was 15. Significant differences were found in the Constant score in individuals under 60 years of age, but they were not significant considering the type of fracture or the DASH score. X-rays showed a healing rate of 95.7%, with two cases of pseudarthrosis. Varus healing was observed in 17 patients (38.6%). Functional differences were found when patients with varus healing were compared with those who had anatomical healing. DISCUSSION: Fixation with intramedullary nailing is an effective treatment for fractures of the proximal humerus, particularly for two segment fractures of the surgical neck. The high rate of varus collapse, particularly in very comminuted fractures, may lead to decreased mobility. PMID- 26999968 TI - [Treatment of chronic acromioclavicular joint instability]. AB - The purpose of this paper is to assess the results obtained with the arthroscopy assisted surgical technique for the treatment of chronic acromioclavicular joint instability (CACJI), based on non-rigid coracoclavicular (CC) fixation and anatomical CC reconstruction with a tendinous allograft. Patients with CACJI who underwent surgery between 2008 and 2012 were included in the study. Clinical assessments included SF36, VAS and DASH, applied at the preoperative visit (POV) and at the last follow-up visit (LFUV). The Constant score and the General Satisfaction Score (0-10) were applied at the last follow-up visit. Occurrence of secondary subluxations was assessed. Ten patients were included; mean age was 41 years (range 33-55). Mean follow-up was 25.50 months (range 24-30). Surgical treatment was indicated in all patients after failure of conservative treatment. Questionnaires applied at the POV and the LFUV showed the following results: 1. SF36: physical, POV = 29.60 +/- 3.41 and LFUV = 59.58 +/- 1.98 (p = 0.000); 2. SF36 mental, POV = 46.57 +/- 3.80 and LFUV = 56.62 +/- 1.89 (p = 0.000); 3. VAS: POV = 5.17 +/- 2.40 and LFUV: 1.67 +/- 2.07 (p = 0.022); and 4. DASH: POV = 63.33 +/- 23.56 and LFUV = 2.61 +/- 1.79 (p = 0.000). The Constant score and the general satisfaction at the LFUV were 95.56 +/- 3.28 and 9.22 +/- 0.67, respectively. There were no secondary subluxations. Treatment of CACJI with a CC suspension device and arthroscopically-assisted anatomical reconstruction of CC ligaments may provide a significant quality of life improvement to patients. It is a strategy that, upon considering primary mechanical CC fixation, may minimize the chance of failure and occurrence of secondary subluxations. PMID- 26999970 TI - [Interpretation of the pivot test using accelerometers in the orthopedic practice]. AB - The anterior (A) and posterior (P) cruciate ligaments (CL) of the knee, located inside the joint, connect the femur and the tibia and thus provide stability in the anteroposterior axis of one bone over the other. The anterior cruciate ligament (ACL) may be injured as a result of rotation when practicing a sport involving turning with the foot on the ground. ACL injuries are diagnosed with maneuvers like the Lachman, drawer and pivot. Accelerometers were used to plot the pivot maneuver in patients seeing the orthopedist surgeon using the KT1000 test as gold standard. This case-control descriptive study was approved by the Hospital's Ethics Committee. Results: 92 patients accepted to participate through an informed consent; nine cases were KT1000 positive, and nine age- and gender matched controls were selected among KT1000 negative patients. KT1000 alterations were greater among females (78%) and in 67% of cases the right leg was affected. Mean KT1000 results were 5.44 mm in cases and 0.66 mm in controls. Accelerometers allowed plotting the pivot maneuver and the resulting charts for cases and controls were similar. Remarkable differences were seen only in one male patient with a 15 mm KT1000, who underwent repair of the left ACL; the maneuver was performed under sedation. We concluded that conscious patients oppose the maneuver, unlike anesthetized patients, and that the use of accelerometers helps document the pivot maneuver which, in turn, helps detect differences between a normal ACL and an injured one. PMID- 26999969 TI - [Nontraumatic causes of bilateral avascular necrosis of the femoral head: link between hepatitis C and pegylated interferon]. AB - BACKGROUND: Avascular necrosis of the femoral head is a frequent condition in patients with a history of trauma. The major pathologic causes include vascular diseases, malignancies, hypercoagulability states, long-term steroid treatment, and some patients have a history of hepatitis C infection treated with pegylated interferon and ribavirin. Upon studying the behavior of the hepatitis C virus, Seef, Foster and Poynard found a hypercoagulability state that causes interruption of retinacular blood flow to the femoral head, without an increased incidence of osteonecrosis in this patient group. Lauer states that such viral infections involve an autoimmune process and may result in transient vasculitides. Giampaolo, in 2005, reported the relationship between interferon use for multiple myeloma and other cancers and femoral avascular necrosis. MATERIAL AND METHODS: Cases with a diagnosis of bilateral osteonecrosis of the femoral head were assessed. RESULTS: Five patients were included, 4 females and one male, with a diagnosis of bilateral osteonecrosis of the femoral head. All of them had history of hepatitis C infection treated with pegylated interferon. The final diagnosis was proven by pathology after arthroplasty. A literature review was made of articles on the relationship between this condition and interferon use in patients with hepatitis C infection. CONCLUSIONS: Finding out the relationship between viral diseases such as hepatitis B and C infection and hypercoagulability states, autoimmune processes leading to transient vasculitides and the use of pegylated interferon 2B, will help us discover new nontraumatic causes associated with this condition. PMID- 26999971 TI - [Utility of morphogenetic protein for the treatment of congenital pseudoarthrosis of the tibia]. AB - OBJECTIVE: To report the ability of bone morphogenetic protein to achieve bone healing in patients with congenital pseudoarthrosis of the tibia. PATIENTS AND METHODS: Three patients with a diagnosis of congenital pseudoarthrosis of the tibia were followed-up for six months. Bone healing and functional capacity of the limb were observed. RESULTS: Bone healing occurred in all cases at a mean of three and half months of treatment. CONCLUSIONS: Morphogenetic protein is useful as an adjuvant to achieve bone regeneration and healing in patients with congenital pseudoarthrosis of the tibia. PMID- 26999972 TI - [Tarsal tunnel syndrome secondary to venous insufficiency. Case report]. AB - Tarsal tunnel syndrome is defined as an extrinsic and/or intrinsic compressive neuropathy of the posterior tibial nerve or one of its branches. Its causes include venous insufficiency. Clinical case: 51 year-old female patient from Leon, Guanajuato. Hypertensive, with Guillain-Barre syndrome for eight years, vascular insufficiency and obesity. Her condition started with left ankle and heel pain; she was treated with NSAIDs and rehabilitation and achieved partial improvement. X-rays and MRI of the left ankle showed posterior impingement. She underwent arthroscopy and improved but one month later she presented with severe pain in the left ankle and sole and dysesthesias. Electromyography showed a lesion of the posterior tibial nerve. We had the patient's case history, preoperative tests, and dorsoplantar and lateral X-ray views. The arthroscopic diagnosis was Flexor Hallucis Longus (FHL) tendinitis, synovitis and posterior ankle impingement. Synovectomy, decompression and smoothening of the FHL tendon were performed. The patient did poorly and underwent electromyography with axonotmesis of the medial plantar branch. After the nerve was released, Lazorthes venous plexus was found to be tortuous and compressing the entire nerve tract. The possible causes for this include intrinsic compression secondary to tumors, and anatomical changes of the tarsal tunnel. However, less often varices may confound the diagnosis and cause irreversible damage if not treated timely. The patient is currently pain free and can walk, has mild dysesthesias of the first toe and limited flexion. PMID- 26999974 TI - MACRA: the Medicare physician payment system continues to evolve. PMID- 26999973 TI - [Bone liposclerosing myxofibrous tumor. Case presentation and literature review]. AB - The bone liposclerosing myxofibrous tumor (LSMFT) was initially described by Ragsdale in 1986 as a polymorphic fibroosseous bone lesion with a mix of histologic elements that include lipoma, fibroxanthoma, myxoma, myxofibroma, fat necrosis, ischemic ossification, areas of fibrous dysplasia, and infrequent presence of cartilage or cystic changes. The most frequently reported location is the intertrochanteric area of the femur. Radiologically it is a lytic, geographic lesion, with well-defined margins and usually sclerotic. In some cases findings include mineralization inside the lesion or a certain degree of expansion to the contour. The close relationship between LSMFT and fibrous dysplasia has been described based on the histologic characteristics and the presence of the Gsalpha mutation. Another hypothesis of the etiology of the lesion is the reaction of fibrous dysplasia to stress. PMID- 26999975 TI - Best practice in unbilled account management: one medical center's story. AB - After implementing its new electronic health record, a large metropolitan academic medical center (AMC) decided to optimize its supporting business systems, beginning with billing. By identifying problems and taking the following corrective actions immediately, the AMC significantly reduced the number and average age of its unbilled accounts: Realigning system automation to improve routing efficiency. Facilitating interdisciplinary collaboration to better identify and correct the root causes of issues. Ensuring transparent data reporting by setting up different ways of viewing the underlying information. PMID- 26999976 TI - The EHR evolution: new priorities and implementation challenges. AB - Five types of key leadership decisions can help smooth the process of selecting and implementing EHR systems and upgrades: Balancing choices with population health priorities. Considering approaches to reduce costs and ease implementation. Prioritizing steps to ease physicians' first six months with the system. Implementing all at once to eliminate "clunky" workflows. Staggering a launch to identify quick-to-value features and functions. PMID- 26999977 TI - Responding to the HIT imperative: a guide for independent hospitals. AB - Independent hospitals and small health systems that lack the financial wherewithal to develop an electronic health record system on their own, and that are seeking an alternative strategy, should keep in mind five lessons learned by organizations that have faced a similar challenge: Review the full range of options. Be realistic and acknowledge the importance of strong management. Adhere to a budget. Reach out to peers. Be wary of competitors' offers to help. PMID- 26999978 TI - Shedding light on physician performance transparency. AB - Healthcare providers can use performance data already being collected to: Manage risk more proactively by identifying high-risk, high-cost areas. Make call centers more effective and websites work better, thereby improving the patient experience. Embrace the trend toward consumerism by enabling patients with performance data. Modify behavior and make systemic improvements where weaknesses are identified. Improve the level of care by better matching patients and providers. Regain public trust and confidence by sharing real data as an alternative to subjective commentary on physician performance. PMID- 26999979 TI - Invest in your data: how clinical mobility solutions liberate data and drive cost savings. AB - Smart point-of-care mobile solutions integrate with a health system's existing communications and IT infrastructure to achieve the following benefits: Unify data management and communication functions using a single device. Improve accuracy of data collection, medication administration, and blood collection through scanning and cross-matching. Facilitate data accessibility from electronic health records and clinical protocols. Enable better care-team communication while safeguarding personal health information. Increase accuracy and efficiency, thereby improving performance and satisfaction scores. PMID- 26999980 TI - How streamlining telecommunications can cut IT expense. AB - Hospitals and health systems can save IT expenses by implementing more efficient processes in accordance with the principles of effective telecommunications expense management. This approach involves three primary steps: Inventory of existing infrastructure. Charge verification. Optimization of rates and design for continual improvement. PMID- 26999981 TI - A progress check on 7 aspects of CINs. PMID- 26999982 TI - The continued proliferation and evolution of ACA reforms. PMID- 26999984 TI - [Juan Valverde de Amusco c. 1525-1588 and his vocation for anatomy in the Hispano Italian Renaissance]. AB - The XVIth century witnessed a glorious period in the progress of some of the basic medical sciences among which anatomy stands out. One of the well-known figures involved in the development of this subject was Juan Valverde de Amusco, a notable Spanish scientist. This research shows the most relevant data currently known on his life, sociocultural environment and his celebrated treaty on anatomy titled: "Historia de la composicion del cuerpo humano". (History of the human body). PMID- 26999983 TI - ["Caciquismo" and medical profession: the case of Alfredo Alegre, 1915-1924]. AB - The professional recognition and sanitary reforms that physicians sought from the political powers throughout the constitutional era of the reign of Alfonso XIII were a continuation of those from the XIXth century. One of the most important demands was that rural physicians should answer directly to the State, especially with reference to salaries, rather than to municipal authorities generally held by caciques. There were constant problems between them. This work presents the case of the physician from El Pobo, Alfredo Alegre, whose conviction put health professionals, students and most of society on the warpath, joining their demands to a petition for pardon. This tragic story, apart from showing the importance of the daily press as a source, highlights the difficulties offered by professional practice in rural areas submerged in the past and the inability of politicians to resolve problems during one of the most hectic periods of our history. PMID- 26999985 TI - Effect of Steroid Prophylaxis on Nerve Function Impairment in Multi-bacillary Leprosy Patients on MDT-MB. AB - The effects of corticosteroids in varying doses and duration for the treatment of reaction and nerve function impairment (NFI) in leprosy have been studied extensively. However, an optimal dose and duration of steroid when used as a prophylactic agent for NFI is yet to be established. This study was aimed to determine whether addition of low dose steroid for the initial 8 months of multi drug therapy (MDT) can prevent further deterioration of nerve function (DON) in multibacillary leprosy patients. Sixty multibacillary leprosy patients were randomized into two groups and B consisting of 30 patients each. Group A received MDT-MB for 12 months with prednisolone 20 mg/day from the beginning of treatment for 6 months followed by tapering by 5 mg/2 weeks in 7th and 8th month. Group B received MDT-MB alone for 12 months. Nerve function assessment (NFA) using various modalities was done at the beginning (0 month), at the end of 8 months and at the completion of MDT (12 months). The proportion of patients showing DON was significantly higher in group B, while proportion of patients showing improvement was more in group A. This study thus shows all MB cases with or without NFI at registration should receive prophylactic steroid at least for 8 months. Since preventing deformities using; prophylactic steroids in leprosy is an important issue larger randomized control trials using longer duration of low dose steroid witha longer follow up period should be conducted. PMID- 26999986 TI - Socio-Economic and Health Status of Leprosy Affected Person: A Study in Jharkhand. AB - The study has been conducted in the Potka Block of East Singhbhum district of the state of Jharkhand. The district is mainly dominated by indigenous tribes, such as, Santhal, Munda, Ho, Bhumiz, Kharia, and Sabar. The unit of analysis of the study was an individual. The objectives were to: a) Understand the socio-economic and health status of LAP, b) Know the health seeking behavior and problems faced by the LAP, c) Assess the utilization of the programs related to Leprosy eradication in the study area and d), Suggest various measures for improving the socio-economic and health status of LAP. Fifty Leprosy affected persons (LAP) from the Potka block; comprising of 20% of LAP of that area have been selected as the study sample by using the method of Multi-Stage Random Sampling, with equal representation of men and women. The LAPs included leprosy patients, leprosy treated people and their family members. 39/50 (78%) of the respondents are illiterates and only 3/11 (6%) among the literate population have crossed matriculation and above. This seems to have resulted in the respondent's low level of awareness about the disease, resulting in delayed treatment. 14/25 (56%) percent of female and 13/25 (52%) of male respondents are considered untouchable by their natal families, thus forced to stay in congested leprosy colonies resulting in other social and health related issues. It was observed that leprosy cured children,and also children of LAP are being denied admission iany school, due to the social stigma attached to it. 27/50 (54%)of leprosy patients and leprosy cured people (mostly with visible deformities) were found to practice begging as their sole means of livelihood. Many LAPs are also engaged in cultivation and small scale business particularly among the rural population. An amount of gender disparity was also observed in the employment pattern among the LAPs. Among the, respondents 15/25 (60%) of the females are beggars as compared to 12/25 (48%) of the male respondents, 5/25 (25%) of males are each engaged in cultivation and small scale businesses in comparison to 1/25 (4%) of female and 6/25 (24%) of the female respondents are unemployed as compared to 2/25 (8%) of male respondents. It was observed that only 30% of the respondents were satisfied with the government treatment, 26% partially satisfied and rest were not satisfied with the government leprosy care system. Most of them wanted to seek treatment from the private health care providers. Overall this study reflects the poor socio-economic conditions of the LAPs. Though results of this exploratory study cannot be extrapolated to country or region or state without studying the situation in detail, it highlights the need for more in-depth studies and of government intervention in the form of encouraging awareness activities in the communities, engaging NGOs im case detection and after care service provision and rehabilitation of the LAPs. PMID- 26999987 TI - Disclosure of Leprosy by Health Care Providers in South-India: Patients' Perception and Relevance to Leprosy Control, Tamil Nadu. AB - Stigma, isoIation and discrimination are typically associated with diagnosis of leprosy and its disclosure. Health care providers (HCPs) find it challenging to disclose the diagnosis of leprosy to patients and their family members. A qualitative study was done in a rural community near Chennai in Tamil Nadu, from August 2011 to March 2012, covering 155 out of 648 (23.9%) purposively selected leprosy patients from 53 out of 148 panchayats, representing 264 villages in the study area; Out of these 155 patients, 59% were males; 30% were illiterates; 70% were married; 56% were living in nuclear families; half the leprosy patients were either agricultural labourers or skilled workers (50%).Thirty two percent were multibacillary (MB) cases and 68% were pauci bacillary (PB) cases; 77% were old patients and 23% were new patients; 22% had leprosy deformity 12% had disfiguration; 23% had anaesthesia and 3% were with lagophthalmous. Of the 155 patients, 31 (20%) reported that they were not informed about diagnosis of their disease by the concerned HCPs. They were informed to be having a skin disease or a skin patch. Of these 31 patients, 22 (71%) were women; all except one with PB leprosy. Seven patients (23%) had not yet started on treatment 3 patients (10%) were given treatment when they were young and neither, them nor their parents were informed about this disease. Seven (33%) of the married patients who had the disease during their child had or when they were young, were not informed of the diagnosis by the HCPs. Ten respondents (32%) were neither bothered nor concerned about non disclosure of the disease by HCPs. Now, after knowing the diagnosis of the disease 4 females (13%) mentioned that they were having some fear, worry or stigma. As non-disclosure of leprosy by HCPs may adversely affect acceptance and adherence, to treatment by the patients, appropriate communication strategies should be developed and implemented. PMID- 26999988 TI - Early Onset Dapsone-induced Photosensitive Dermatitis: A Rare Side Effect of a Common Drug. AB - Dapsone, a potent anti-inflammatory compound, is mainly used in the treatment of leprosy, dermatitis herpetiformis, erythema elevatum diutinum and other dermatoses. Cutaneous adverse reactions range from acneiform eruptions to toxic epidermal necrolysis. A 30-year-old, married women who was treated with paucibacillary multi drug therapy, developed itchy skin lesions over the both forearms, 'V ' area of the neck and upper back after one week of the drug administration which worsened on exposure to sunlights. A clinical diagnosis of dapsone-induced photosensitive dermatitis was confirmed by histopathology and recurrence of symptoms and signs after re-exposure to the drug. Photosensitivity due to dapsone is rare and very few reports are available in the literature. Our patient had an unusually early onset compared to the previously reported cases. PMID- 26999989 TI - Ileofemoral Deep Vein Thrombosis (DVT) in Steroid Treated Lepra Type 2 Reaction Patient. AB - In 1998 a 57-year-old man having skin leisons of 6 months duration reported to Central Leprosy Teaching and Research Institute (CLTRI), Chengalpattu. It was diagnosed as a case of borderline lepromatous leprosy with a type 2 lepra reaction, was treated with multi bacillary-multi drug therapy (MBMDT) for a period of 12 months and the patient was released from treatment (RFT) in September 1999. For reactions the patient was treated with prednisolone for more than 10 months. After 14 years in April 2013 the same patient presented to CLTRI with complaints of weakness of both hands with loss of sensation for 4 months, so making a diagnosis suggestive of MB relapse with neuritis the patient was started with MB-MDT for period of 12 months with initial prednisolone 25 mg OD dose then increased to 40 mg for painful swollen leg and to follow the neuritis associated pain and swelling. Increased dose is not beneficial and the patient was investigated for other pathology. Doppler ultra-sound revealed a left ileofemoral deep vein thrombosis (DVT) in that patient with levels. Prednisolone was withdrawn and the patient was started with anticoagulant heparin followed by warfarin. During this period rifampicin was also withdrawn. After patient was in good condition he was put on MB-MDT regimen. Till the 6th pulse the patient continues to show improvement in functions without steroids and any tenderness, he is taking multivitamins; regular physiotherapy. This DVT appears to be due to prednisolone and such causative relationship though rare should be kept in mind when patient on long term treatment with steroids/and or immobilized or on prolonged bed rest report with such symptomatology. PMID- 26999990 TI - Primary Neuritic Hansen's Disease presenting as Ulnar Nerve Abscess in a Human Immunodeficiency Virus Positive Patient. AB - Leprosy has been increasingly known to have an enigmatic relationship with human immunodeficiency virus infection. Co-infection may result in atypical manifestations of leprosy. A 45-year old human immunodeficiency virus-positive male; agricultural laborer presented with a swelling over right elbow, right hand deformity, generalized itching and recurrent vesicles overthe perinasal area. Clinical and investigational findings were consistent with mononeuritic type of Hansen's disease with right sided silent ulnar nerve abscess, partial claw hand. CD4+ count of the patientwas 430 cells/cmm. This patient also hadherpes simplex labialis, with HIV-associated pruritus. To the best of our knowledge such an atypical presentation has not been reported earlier. PMID- 26999991 TI - "Be the change you want to see in the world". PMID- 26999992 TI - [You women...]. PMID- 26999993 TI - [Diagnosis, management and treatment of chylothorax]. AB - Chylothorax is characterized by a milky pleural effusion that results from the injury to the thoracic duct, causing leakage of chyle into the pleural space. Its diagnosis relies primarily, on the determination of triglycerides and/or the identification of chylomicrons in the pleural fluid. The most common causes are traumatic, mainly after surgery. Among non-traumatic causes, tumors are the most frequent (like lymphomas). Conservative treatment is based on pleural drainage with a low fat diet and appropriate etiological approach. In case of failure, occlusion of the thoracic lymph duct should be considered, either by a surgical approach or interventional radiology. PMID- 26999994 TI - [Sputum purulence: practical guide to introduce antibiotic therapy]. AB - In the collective unconscious of doctors and patients, purulent sputum is correlated with bacterial infection requiring antibiotics. The introduction of antibiotic therapy in a patient with purulent sputum is legitimate only in certain situations. The presence of purulent sputum during a mild infection of the upper airways does not generally justify the introduction of antibiotic treatment. In patients with chronic respiratory diseases, studies have shown that purulent sputum is often associated with a secondary bacterial infection and antibiotic therapy may provide clinical benefit. PMID- 26999995 TI - [Renal colic: new care in emergency centers]. AB - The prevalence of renal colic is increasing in industrialized countries, representing a frequent reason for consultation in emergencies. Most patients have simple renal colic that will require analgesia and ambulatory monitoring. Doctors working in emergency centers play a key role in the diagnosis, care and guidance of these patients. They must identify factors of gravity and request urological advice if necessary. This article summarizes the recent diagnostic and therapeutic innovations in the management and guidance of renal colic in emergency centers. PMID- 26999996 TI - [Bone tuberculosis: when consider this diagnosis?]. AB - The most common presentation of bone tuberculosis (TB) is called spondylodiscitis, or "Pott's disease", which is a difficult diagnosis due to its low prevalence in Switzerland. It should be considered in patients with persistent back pain, who are at high risk, such as migrant population and immunocompromised patients. Diagnosis is based on imaging and the detection of M. tuberculosis in biopsy of affected vertebra orparaspinal abscess, or even if active tuberculosis is proven in any other site. It's essential to initiate appropriate treatment as quickly as possible in order to avoid neurological complications and spinal deformity and to identify cases that will require a surgical therapy. PMID- 26999997 TI - [Reverse shoulder arthroplasty]. AB - Shoulder pain is a common problem for general practitioners. The objectives of a shoulder arthroplasty are to improve the articular function and to provide pain relief. Anatomic shoulder arthroplasty is not the treatment of choice if a rotator cuff deficiency is associated with arthritis. In some circumstances (muscle or tendon deficiency) rotator cuff repair is technically impossible. Reverse shoulder arthroplasty (RSA) has opened new opportunities for patients suffering with shoulder conditions such as shoulder pseudoparalysis and revision surgery. RSA is rarely proposed to patients below the age of 60 but thereafter there is no age limit. With this procedure, the functional improvement can be achieved after days or weeks. A new surgical approach allows for early active mobilization without a specific rehabilitation period. PMID- 26999998 TI - [Sodium chloride 0.9%: nephrotoxic crystalloid?]. AB - Sodium chloride 0.9%, often incorrectly called physiological saline, contains higher concentration of chloride compared to plasma. It is known that the administration of sodium chloride 0.9% can cause hyperchloremic metabolic acidosis in a reproducible manner. The elevated chloride concentration in 0.9% NaCl solution can also adversely affect renal perfusion. This effect is thought to be induced by hyperchloremia that causes renal artery vasoconstriction. For these reasons, the use of 0.9% NaCl solution is raising attention and some would advocate the use of a more "physiological" solution, such as balanced solutions that contain a level of chloride closer to that of plasma. Few prospective, randomized, controlled trials are available today and most were done in a perioperative setting. Some studies suggest that the chloride excess in 0.9% NaCl solution could have clinical consequences; however, this remains to be established by quality randomized controlled trials. PMID- 26999999 TI - [Multidisciplinary consultation "Suffering at work": an experience in western Switzerland]. AB - Mental health problems at work constitute a challenge in the clinical feld, as well in the professional, the economic and the public health perspective. The total costs they generate in Switzerland are equivalent to 3.2% of the Swiss gross domestic product and they very often lead to dismissal. The vast majority of people are treated by their primary care physician. The Institute for Work and Health features a specialized consultation on the topic of suffering at work, offering the primary care physicians a pluridisciplinary advice or support, in a collaborative care prospect. Its action, adapted to each situation's needs, goes from an advice to a referral to specialists that can strengthen the network on a long-term basis (mental health follow-up, supported employment program, legal or social advice). PMID- 27000000 TI - [Shortage of doctors in Switzerland: myth or reality?]. PMID- 27000001 TI - [The American Zika epidemic, or the medicine side to religion]. PMID- 27000002 TI - [Limited]. PMID- 27000003 TI - [Prophylaxis of pediatric HIV infection: what to do after the success?]. PMID- 27000004 TI - [Elderly and medicalized, digital and film miscellany]. PMID- 27000005 TI - [Big increase in the frequency of pediatric emergencies]. PMID- 27000006 TI - [At HUG, visitors must wear a mask]. PMID- 27000007 TI - [Perfection versus imperfection]. PMID- 27000008 TI - Cost and mortality data of a regional limb salvage and hyperbaric medicine program for Wagner Grade 3 or 4 diabetic foot ulcers. AB - We obtained costs and mortality data in two retrospective cohorts totaling 159 patients who have diabetes mellitus and onset of a diabetic foot ulcer (DFU). Data were collected from 2005 to 2013, with a follow-up period through September 30, 2014. A total of 106 patients entered an evidence-based limb salvage protocol (LSP) for Wagner Grade 3 or 4 (WG3/4) DFU and intention-to-treat adjunctive hyperbaric oxygen (HBO2) therapy. A second cohort of 53 patients had a primary lower extremity amputation (LEA), either below the knee (BKA) or above the knee (AKA) and were not part of the LSP. Ninety-six of 106 patients completed the LSP/HBO2with an average cost of USD $33,100. Eighty-eight of 96 patients (91.7%) who completed the LSP/HBO2had intact lower extremities at one year. Thirty-four of the 96 patients (35.4%) died during the follow-up period. Costs for a historical cohort of 53 patients having a primary major LEA range from USD $66,300 to USD $73,000. Twenty-five of the 53 patients (47.2%) died. The difference in cost of care and mortality between an LSP with adjunctive HBO2therapy vs. primary LEA is staggering. We conclude that an aggressive limb salvage program that includes HBO2 therapy is cost-effective. PMID- 27000009 TI - Performance of three large-volume infusion pumps with the monoplace hyperbaric chamber. AB - We evaluated the Zyno Medical Z-800F, CME Body Guard 323 Color Vision, and Baxter Flo-Gard 6201 infusion pumps for monoplace chamber conditions. We adjusted pump occlusion pressure allowing infusion to 3 atmospheres absolute (atm abs). Baxter and Zyno pumps were connected to the chamber pass-through with rigid small-bore tubing. The CME infusion set was connected directly to the pass-through. We infused saline to a collection manifold inside a monoplace chamber at 1-100 mL/ hour under pressures ranging from 0.85-3.0 atm abs. We averaged results from three to five separate tests for each condition. At baseline, pumps performed within +/-10% of expected (our measurement capability). However, clinical engineering verified performance within manufacturer specifications (+/-5% at atmospheric pressure). During a carbon monoxide hyperbaric protocol (3 atm abs/2 atm abs), measured flow with the Baxter, CME and Zyno pumps was +/-5% of setting at 10 mL/hour (95%, 103%, 95%, respectively); at 1 mL/hour, average flow were 91%, 83%, 83%, respectively. During timed testing (volume recorded before decompression), pump accuracy was +/-10% at 10 and 100 mL/hour. Tubing compliance compromised performance at lower flow rates, magnified by increased pressure. These pumps have potential for monoplace chamber use, although not supported by the manufacturers or FDA-cleared. At low flow rates, tubing compliance affects delivered volumes. PMID- 27000010 TI - Seizures during hyperbaric oxygen therapy: retrospective analysis of 62,614 treatment sessions. AB - INTRODUCTION: Hyperbaric oxygen (HBO2) therapy is considered to be a generally safe therapy. However, data regarding seizure incidence during HBO2 therapy as a clinical presentation of central nervous system- (CNS) related oxygen toxicity are conflicting (ranging from 1:10,000 to 1:600 seizures:hyperbaric sessions). The risk for seizures is of significant importance for the growing population of patients suffering from chronic neurological disorders such as traumatic brain injury and stroke who are treated with HBO2. The aim of this study was to evaluate the incidence of seizures during HBO2 therapy in a large cohort of patients and determine whether patients with known chronic neurological disorders are at increased risk. METHODS: Retrospective analysis of 2,334 patients treated at the Sagol Center of Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Israel, between June 2010 and December 2014. Patients were grouped into one of three categories according to indication for HBO2 therapy: Category A--non neurological indications; Category B--neurological indications; and Category C- acute indications. RESULTS: A total of 62,614 hyperbaric sessions, administered to 2,334 patients, were included in the analysis. The overall incidence of seizures during hyperbaric sessions was 0.011% (1:8,945), occurring in seven (0.3%) patients. Only one patient had a clear oxygen toxicity-induced seizure, with an overall incidence of 1:62,614. CONCLUSIONS: Seizures induced by oxygen toxicity during HBO2 therapy are extremely rare. Moreover, in relation to oxygen induced seizures, HBO2therapy can be considered safe for patients suffering with chronic neurological disorders except for uncontrolled epilepsy. PMID- 27000011 TI - Hyperbaric programs in the United States: Locations and capabilities of treating decompression sickness, arterial gas embolisms, and acute carbon monoxide poisoning: survey results. AB - Hyperbaric oxygen therapy is the primary treatment for arterial gas embolism, decompression sickness and acute carbon monoxide poisoning. Though there has been a proliferation of hyperbaric centers throughout the United States, a scarcity of centers equipped to treat emergency indications makes transport of patients necessary. To locate and characterize hyperbaric chambers capable of treating emergency cases, a survey of centers throughout the entire United States was conducted. Using Google, Yahoo, HyperbaricLink and the UHMS directory, a database for United States chambers was created. Four researchers called clinicians from the database to administer the survey. All centers were contacted for response until four calls went unreturned or a center declined to be included. The survey assessed chamber readiness to respond to high-acuity patients, including staff availability, use of medical equipment such as ventilators and intravenous infusion devices, and responding yes to treating hyperbaric emergencies within a 12-month period. Only 43 (11.9%, N = 361) centers had equipment, intravenous infusion pumps and ventilators, and staff necessary to treat high-acuity patients. Considering that a primary purpose of hyperbaric oxygen therapy is the treatment of arterial gas embolism and decompression sickness, more hyperbaric centers nationwide should be able to accommodate these emergency cases quickly and safely. PMID- 27000012 TI - Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production. AB - It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production. PMID- 27000013 TI - The use of hyperbaric oxygen therapy for carbon monoxide poisoning in Europe. AB - BACKGROUND: The aim of this survey was to identify practice differences in the treatment of carbon monoxide (CO) poisoning with hyperbaric oxygen (HBO2) therapy among centers in Europe. MATERIALS AND METHODS: Using a commercial online survey website (surveymonkey.com), we created a questionnaire and invited the medical directors of hyperbaric centers in Europe by email to complete the survey. RESULTS: Sixty-eight centers from 23 countries participated in the survey. While transient or prolonged unconsciousness was unanimously recognized as an indication for HBO2 therapy, positive neurological findings, ECG suggesting acute ischemia and pregnancy were considered important indications of HBO2 therapy in more than 95% of the centers. Twenty-three (44%) centers reported that they used carboxyhemoglobin (COHb) levels as a criterion for patient selection. Among responders, 39% (18/46) reported delivering a single session within the first 24 hours of CO poisoning, and nine (19%) reported delivering three sessions in the first day. The majority of the centers (52%) replied that they initially gave a single session per patient, which was repeated if symptoms persisted. We identified a total of 21 different HBO2 profiles used in European centers. CONCLUSION: Our results showed that the indications of CO poisoning for HBO2 therapy are still not universally recognized. Additionally, HBO2 therapy protocols used at European hyperbaric centers varied significantly, suggesting a need for more education regarding the published guidelines. PMID- 27000014 TI - Inaccurate pulse CO-oximetry of carboxyhemoglobin due to digital clubbing: case report. AB - Newer pulse CO-oximeters provide a non-invasive and quick means of measuring oxyhemoglobin, carboxyhemoglobin and methemoglobin. Clubbing has been reported to cause inaccuracy in pulse oximeters. We present a case of inaccurate carboxy hemoglobin measurement by pulse CO-oximetry due to digital clubbing. An 18-year old man with a history of cystic fibrosis presented after a suicide attempt by inhalation of exhaust. At the initial emergency department evaluation, his blood carboxyhemoglobin was 33%. He was intubated, placed on 100% oxygen and transferred to our facility. Upon arrival, we placed three different pulse CO oximeters on different fingers and toes. Carboxyhemoglobin levels measured by these meters ranged from 9%-11%. A venous blood gas drawn on arrival showed a carboxyhemoglobin level of 2.3% after four hours on 100% oxygen by endotracheal tube. Thirty minutes later, we checked arterial blood gas, which revealed a COHb level of 0.9%. Again, non-invasive carboxyhemoglobin measurements read 10%. The patient was treated with hyperbaric oxygen for carbon monoxide poisoning. This case suggests that non-invasive measurements of carboxyhemoglobin should be correlated with the clinic history and with an arterial or venous blood gas oximetry analysis. PMID- 27000015 TI - Carbon monoxide and ST-elevation myocardial infarction: case reports. AB - We describe two cases of myocardial infarction with ST-segment elevation on electrocardiogram associated with carbon monoxide (CO) poisoning, a condition rarely reported in the literature. The first was a 62-year-old woman who experienced chest pain in the emergency department (ED) while being assessed for exposure to carbon monoxide in her home. The second was an 80-year-old man who fainted at home and was found to have ST elevation during the ED workup. After hospitalization, he returned home and soon thereafter had difficulty walking and speaking. The responding paramedics detected a very high CO level in the home. Both patients received hyperbaric oxygen therapy within the first several hours of presentation. For this combination of conditions, it is difficult to derive evidence-based management recommendations, given the paucity of cases reported to date. We conclude that rapid consultation with interventional cardiology and consideration of angioplasty or stenting are appropriate, especially when electrocardiographic findings and echocardiography point to a specific coronary distribution. Hyperbaric oxygen therapy might have a role in the treatment, based on its effects on myocardial ischemia and injury in other models. PMID- 27000016 TI - Treatment of cardiac arrest in the hyperbaric environment: key steps on the sequence of care--case reports. AB - The U.S. territory of Guam attracts thousands of military and civilian divers annually and is home to the only recompression facility within a 5,000-km radius that accepts critically injured dive casualties. As recompression chambers are confined spaces and standard use of electrical cardioversion cannot be used, cardiac resuscitation at depth must deviate from advanced cardiovascular life support (ACLS) algorithms. Furthermore, many hyperbaric chambers that accept dive casualties are in remote locations, a situation that requires providers to approach cardiac resuscitation in a different way when compared to an in-hospital or ICU setting. This presents a challenge to trained medical and diving professionals. We present two contrasting vignettes of diving injuries initially responsive to appropriate treatment but then deteriorating during recompression therapy and ultimately requiring resuscitation at depth. Additionally, we explore the physiologic basis of resuscitation in a hyperbaric environment as it relates to the treatment of cardiac arrest at depth. This review critically examines the current guidelines in place for emergency cardiac resuscitation in a hyperbaric chamber followed by recommendations for the key steps in the sequence of care. PMID- 27000017 TI - Switch from Sodium Phenylbutyrate to Glycerol Phenylbutyrate Improved Metabolic Stability in an Adolescent with Ornithine Transcarbamylase Deficiency. AB - A male patient, born in 1999, was diagnosed with ornithine transcarbamylase deficiency as neonate and was managed with a strict low-protein diet supplemented with essential amino acids, L-citrulline, and L-arginine as well as sodium benzoate. He had an extensive history of hospitalizations for hyperammonemic crises throughout childhood and early adolescence, which continued after the addition of sodium phenylbutyrate in 2009. In December 2013 he was switched to glycerol phenylbutyrate, and his metabolic stability was greatly improved over the following 7 months prior to liver transplant. PMID- 27000018 TI - Renal abnormalities among HIV infected children at Muhimbili National Hospital (MNH)-Dar es Salaam, Tanzania. AB - BACKGROUND: Human Immunodeficiency Virus infection is a multisystem disease that contributes to significant morbidity. Renal involvement is reported to be common among patients with HIV. This study was carried out to determine renal involvement using simple bedside tests combined with ultrasonography examination. METHODS: We recruited 240 children from the HIV clinic at Muhimbili National Hospital. Data were collected using structured questionnaires and included demographic, clinical information, radiological tests; renal ultrasound and laboratory tests; serum creatinine, white blood cells, CD4+ counts and percent, urine for microalbuminuria and proteinuria. RESULTS: Microalbuminuria and proteinuria were present in 20.4 % and 7.1 % respectively. Significantly higher prevalence of microalbuminuria (p < 0.01) and proteinuria p < 0.01) were noted with low CD4 percent (<25 %). Lower mean CD4+ count were noted among children with microalbuminuria [937.4 +/- 595.3 cells/MUL vs 1164.7 +/- 664.3 cell/MUL, (p < 0.05)] and proteinuria [675.5 +/- 352.3 cells/MUL vs 1152 +/- 662 cells/MUL (p < 0.001)]. Fourteen (5.8 %) HIV infected children had estimated glomerular filtration rate (eGFR of 30-59) consistent with severe renal impairment. Increased cortical echogenicity was noted in 69/153 (39.2 %) of participants who had ultrasound examination. CONCLUSION: Microalbuminuria, proteinuria and renal dysfunction were noted to be prevalent among HIV infected children indicating the need to consider routine screening of renal complications in these children. PMID- 27000019 TI - Osteocalcin gene polymorphism and bone density in Hungarian athletes. AB - SUMMARY: Osteoporosis, a public health problem, is mainly determined on the basis of bone mineral density (BMD). The rs1800247 polymorphism of the osteocalcin gene is associated with BMD. The results of one recent Polish study led us to the examination of a possible connection between polymorphism and bone ultrasound parameters in the Hungarian population, including elite athletes. A total of 302 subjects participated in the study. Genotype analysis was carried out via a DNA chip, and anthropometric measurements were taken according to the International Biological Program. Sixty-three (63) of the participants were also measured by ultrasound bone densitometer. The genotype frequencies of osteocalcin polymorphism in the total sample were: 59.9% for hh; 36.1% for Hh; and 3.97% for HH. We separated the 63 subjects by the presence or absence of H allele, and there were no significant differences between the two groups, either in the anthropometric, or in the ultrasound parameters. In grouping the sample by genotypes, no differences were detectable in any of the bone characteristics. Compared to the controls, athletes had significantly higher results in all of the bone ultrasound values. The polymorphism of the osteocalcin gene showed no effect on bone quantity in the examined Hungarian population. PMID- 27000020 TI - Development of New Effective Sorbents Based on Nanomagnetite. AB - Magnetic hybrid nanocomposite material based on the kraft lignin was prepared by the co-precipitating method. Kraft lignin was modified by iron nanooxide in order to enhance its sorption properties towards heavy metal ions. The composite material was characterized by physicochemical methods such as BET N2, ATR-FTIR, TGA, DSC, pHpzc, XRD and SEM. Its adsorption behaviour was studied using the batch mode by varying different parameters like pH, initial concentration of metal ions and shaking time as well as the presence of interfering ions. Adsorption of Cu(II), Cd(II) and Pb(II) ions from the aqueous solutions was studied in comparison with the commercial kraft lignin. The adsorption capacity and kinetic sorption characteristics of the composite material were determined. PMID- 27000021 TI - Structural and Morphological Features of Disperse Alumina Synthesized Using Aluminum Nitrate Nonahydrate. AB - Transformation of Al(NO3)3?9H2O (upon heating in the range of 20-1200 degrees C) into blends of amorphous and crystalline boehmite (210-525 degrees C), amorphous alumina and crystalline gamma-Al2O3 (850 degrees C), and crystalline alpha-Al2O3 (1100 degrees C) was analyzed using X-ray diffraction (XRD), high-resolution transmission electron microscope (HRTEM), infrared (IR) spectroscopy, thermogravimetry, and low-temperature nitrogen adsorption. Boehmite consists of nanoparticles of 6-10 nm in diameter, and part of them has crystalline structure observed in HRTEM images, despite they are XRD amorphous. The nanoglobules are surrounded by amorphous aluminum hydroxide with chains of -AlO(H)-O-AlO(H)- of 1 5 nm in length. Heating of samples at 350-525 degrees C gives mesoporous aluminum hydroxide with a relatively narrow pore size distribution. An increase in calcination temperature to 850 degrees C decreases the porosity of alumina composed of amorphous and crystalline (gamma-Al2O3) phases. Calcination at 1100 degrees C gives alpha-Al2O3 with strongly decreased porosity of aggregates. PMID- 27000022 TI - Ferromagnetism in Transitional Metal-Doped MoS2 Monolayer. AB - Manipulating electronic and magnetic properties of two-dimensional (2D) transitional-metal dichalcogenides (TMDs) MX2 by doping has raised a lot of attention recently. By performing the first-principles calculations, we have investigated the structural, electronic, and magnetic properties of transitional metal (TM)-doped MoS2 at low and high impurity concentrations. Our calculation result indicates that the five elements of V-, Mn-, Fe-, Co-, and Cu-doped monolayer MoS2 at low impurity concentration all give rise to the good diluted magnetic semiconductors. By studying various configurations with different TM-TM separations, we found that the impurity atoms prefer to stay together in the nearest neighboring (NN) configuration, in which the doped TM atoms are FM coupling except for Fe doping at 12 % concentration. For V, Mn, and Fe doping, the total magnetic moment is smaller than the local magnetic moment of the dopants because the induced spins on the nearby host atoms are antiparallel to that of the doped atoms. In contrast, Co and Cu doping both give the higher total magnetic moment. Especially, Cu doping induces strong ferromagnetism relative to the local spins. However, the atomic structures of Co- and Cu-doped MoS2 deviate from the original prismatic configuration, and the magnetic moments of the doped systems decrease at 12 % impurity concentration although both elements give higher magnetic moments at 8 % impurity concentration. Our calculations indicate that V and Mn are promising candidates for engineering and manipulating the magnetism of the 2D TMDs. PMID- 27000023 TI - The Effect of VMoS3 Point Defect on the Elastic Properties of Monolayer MoS2 with REBO Potentials. AB - Structural defects in monolayer molybdenum disulfide (MoS2) have significant influence on the electric, optical, thermal, chemical, and mechanical properties of the material. Among all the types of structural defects of the chemical vapor phase-grown monolayer MoS2, the VMoS3 point defect (a vacancy complex of Mo and three nearby S atoms) is another type of defect preferentially generated by the extended electron irradiation. Here, using the classical molecular dynamics simulation with reactive empirical bond-order (REBO) potential, we first investigate the effect of VMoS3 point defects on the elastic properties of monolayer MoS2 sheets. Under the constrained uniaxial tensile test, the elastic properties of monolayer MoS2 sheets containing VMoS3 vacancies with defect fraction varying from 0.01 to 0.1 are obtained based on the plane anisotropic constitutive relations of the material. It is found that the increase of VMoS3 vacancy concentration leads to the noticeable decrease in the elastic modulus but has a slight effect on Poisson's ratio. The maximum decrease of the elastic modulus is up to 25 %. Increasing the ambient temperature from 10 K to 500 K has trivial influences on the elastic modulus and Poisson's ratio for the monolayer MoS2 without defect and with 5 % VMoS3 vacancies. However, an anomalous parabolic relationship between the elastic modulus and the temperature is found in the monolayer MoS2 containing 0.1 % VMoS3 vacancy, bringing a crucial and fundamental issue to the application of monolayer MoS2 with defects. PMID- 27000024 TI - Low-Frequency Self-Powered Footstep Sensor Based on ZnO Nanowires on Paper Substrate. AB - In this work, we design and fabricate a wireless system with the main operating device based on zinc oxide (ZnO) nanowires. The main operating device is based on piezoelectric nanogenerator (NG) achieved using ZnO nanowires grown hydrothermally on paper substrate. The fabricated NG is capable of harvesting ambient mechanical energy from various kinds of human motion, e.g., footsteps. The harvested electric output has been used to serve as a self-powered pressure sensor. Without any storage device, the signal from a single footstep has successfully triggered a wireless sensor node circuit. This study demonstrates the feasibility of using ZnO nanowire piezoelectric NG as a low-frequency self powered sensor, with potential applications in wireless sensor networks. PMID- 27000025 TI - Parametric Simulations of Slanted 1D Photonic Crystal Sensors. AB - Photonic crystals and band gap materials act as manipulators of light and have a plethora of applications. They are made up of stacks of alternating dielectric constants. This article shows the simulations of an inclined, one dimensional and tuneble photonic crystal, using numerical finite element methods. The photonic crystal was made up of silver nanoparticles embedded in a hydrogel matrix and it has the ability to change and recover its periodicity. A series of factors concerning the geometry of the lattice were tested in order to analyze the efficiency, performance and optimize the properties of the optical sensor. These factors range from the size of the nanoparticles and their density within the stacks, to observing the effect of diffraction angle in readouts. PMID- 27000026 TI - Porous TiO2 Assembled from Monodispersed Nanoparticles. AB - Porous TiO2 were assembled by evaporating or refluxing TiO2 colloid, which was obtained by dispersing the TiO2 nanoparticles with a crystallite size (d XRD) of 3.2 nm into water or ethanol without any additives. Porous transparent bulk TiO2 was obtained by evaporating the TiO2-C2H5OH colloid at room temperature for 2 weeks, while porous TiO2 nanospheres were assembled by refluxing the TiO2-H2O colloid at 80 degrees C for 36 h. Both of the porous TiO2 architectures were pore-size-adjustable depending on the further treating temperature. Porous TiO2 nanospheres exhibited enhanced photocatalysis activity compared to the nanoparticles. PMID- 27000027 TI - Zero-Order Controlled Delivery of Gliclazide from Polyethylene Oxides Matrix Tables: In vitro and In vivo Evaluation. AB - BACKGROUND: In recent years, controlled and sustained release drug delivery system has become the focus of pharmaceutical researchers. Some technologies aimed to develop the controlled and sustained release of the drug, which used to be administered several times a day and generate plasma concentration fluctuation. As all, a controlled drug release rate has always been a goal pursued by researchers. This paper introduced a controlled delivery hydrophilic matrix system, and evaluated their relevance between in vitro and in vivo behaviors. METHODS: The matrix tablets were fabricated by direct powder compression method. Single-factor test and the orthogonal experimental design were used to find out the optimal formulation. And the in vivo pharmacokinetics study was also evaluated in this paper. RESULTS: The amount of WSR N301 and low viscosity materials significantly affect the drug release. Compared with commercially available sustained-release tablets Diamicron(r), the pharmacokinetics parameters of these matrix tablets exhibited similar blood profiles, and other parameters such as prolonged Tmax, Cmax, MRT and similar bioavailability. However, this matrix system showed unstable blood profiles in comparison with two-layer-core osmotic pump tablet. The IVIVC study suggested that there was a good correlation between absorption in vivo and drug release in vitro. CONCLUSION: Zero-order controlled drug release of hydrophilic matrix system has the simpler manufacture process. And it will be a promising system to control drug release. Due to the disadvantage of hydrophilic matrix tablets in vivo release, for further research the zero-order delivery of PEO matrix tablets system, some pharmaceutical technology are needed to decrease the influence of gastrointestinal peristalsis. Therefore, the study of polyethylene oxide hydrophilic matrix tablets provides a promising formulation for promoting the development of a drug delivery system. PMID- 27000028 TI - Effect of Variation in Viscosity Grade of Ethycellulose on Theophylline Microcapsule Properties Prepared by Emulsion Solvent Evaporation. AB - BACKGROUND: There are conflicting reports regarding the effect of polymer viscosity grade on microcapsule properties. The aim of the present study was to investigate the effect of just viscosity grade of ethylcellulose (EC) (not polymeric solution) on properties of theophylline microcapsules prepared by emulsion solvent evaporation. METHODS: The effect of EC viscosity grade and drug:polymer ratio was investigated on microcapsule properties (yield, particle size, morphology, surface characteristics and drug release). Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) were implemented to study the interaction and solid state of drug. The microcapsules were compressed in the presence of excipients and drug release was evaluated. RESULTS: The yield of microencapsulation and encapsulation efficiency at 1:1 drug:polymer ratio was dependent on EC viscosity. Microcapsules were spherical with some pores on their surfaces. The number of pores was more and their size was bigger for EC 100 cP microcapsules. Theophylline remained in crystalline form after encapsulation. DSC studies confirmed lack of interaction between drug and polymer. The drug release was rapid at 2:1 drug:polymer whilst it was slowed down at 1:1 drug:polymer ratio. Microcapsules obtained from EC 100 cP showed slightly faster drug release at latter ratio. Marginal changes in release rate were observed after compression of microcapsules. CONCLUSIONS: All viscosity grades of EC were able to sustain the release of the drug from microcapsules. Considering the similar release profiles for microcapsules prepared from different viscosities of EC, the use of lower viscosity grade of EC is recommended due to the ease of production and also less processing time. PMID- 27000029 TI - Decreased expression and function of sodium-glucose co-transporter 2 from a novel C-terminal mutation: a case report. AB - BACKGROUND: Familial renal glucosuria (FRG) is characterized by persistent glucosuria in the presence of normal serum glucose concentrations, and the absence of other impairments of tubular function. Mutations in the sodium-glucose co-transporter 2 (SGLT2) gene (SLC5A2) are causative of FRG the long-term outcome of which is well know. In the search for potential new drug targets for SGLT2 inhibitors with which to treat the diabetes, expressional and functional studies of SGLT2 have been the focus of attention, but reports of these are rare. Furthermore, it is well known that the alleles in the C-terminal are very important for the expression and function in some genes. However, little is known about the effect of mutation in SLC5A2 C- terminal. CASE PRESENTATION: Here, we identified a FRG patient with urine glucose excretion 7.56 g/day and a novel SLC5A2 missense mutation, c.1891G > A/p.(E631K), by DNA sequencing. Expression and function of the mutant SGLT2 (631 K) fused to green fluorescent protein (GFP) were verified by western blotting, confocal laser microscopy, and transport activity assays in cultured HEK293 cells. Although wild-type SGLT2-GFP and 631 K mutant-GFP fusion proteins were properly expressed in a punctate pattern in the cell membrane, and co-localized with the cell membrane marker DiIC18(3), the expression of the mutant fusion protein was obviously decreased (24 %). Moreover, the uptake activity of the mutant SGLT2 631 K-GFP fusion protein was significantly decreased compared with wild-type (3629 +/- 1082 vs. 7926 +/- 1153, P < 0.001). CONCLUSION: These results suggest that the SLC5A2 C-terminal is very important for protein expression. We speculate that the observed reduced expression of the mutant transporter led to a decrease in transport of the glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3- diazol-4-yl)amino)-2-deoxyglucose. The current study provides a starting point for further investigations of the SGLT2 molecular mechanism in FRG families, and offers functional insights into the development of anti-diabetes drugs. PMID- 27000030 TI - Blood pressure and body composition of rural Oraons of North 24 Parganas, West Bengal, India. AB - SUMMARY: Prevalence of hypertension is increasing among indigenous populations of India. However, the relationship of body composition traits and hypertension among them is not known. Therefore, the objective of the study is to know the incidence of hypertension and associated body composition traits of rural Oraons. Data have been collected on socio-demographic characteristics, few lifestyle variables, anthropometric measurements and blood pressure from 336 adult (126 males and 210 females) Oraons using standard techniques and instruments. BMI, Waist Hip Ratio, Fat Mass, Fat Free Mass were calculated using formulae. Descriptive statistics, stepwise linear and logistic regression were adopted. Higher percentages of males (46.03%) were hypertensive than females (25.71%). Age was one of the significant predictor of systolic and diastolic blood pressure in either sex with or without adjusting lifestyle variables. Fat free mass, waist circumference along with tobacco chewing for males and mid-upper arm circumference, weight for females were significant predictors of systolic and diastolic blood pressure, respectively. The risk factors for hypertension were age and fat free mass, adjusting lifestyle variables for the group. PMID- 27000032 TI - Lateral angle and cranial base sexual dimorphism: a morphometric evaluation using computerised tomography scans of a modern documented autopsy population from Denmark. AB - SUMMARY: Previous studies have yielded very different results in sex estimation based on measurements of the lateral angle (LA) of the temporal bone. The purpose of this study was to, first, investigate if the bad results obtained by the LA method could be due to the methodology and then, second, to examine sexual dimorphism in the relationship between the lateral angle and cranial base shape. The lateral angle method was tested using a forensic sample of 102 CT scans of the head with known sex. We measured the angle using two methods: measurements directly on the CT slide, the method usually applied, and by use of a new method, using a "virtual cast". The cranial base was quantified by placing 12 landmarks in the posterior fossa. Procrustes analysis, principal component analysis, discriminant analysis and cross-validation test were performed. The "cast method" was found to be less accurate than the direct measurements. The mean angle was greater in females (48.2 degrees +/- 7.2 degrees ) than in males (45.38 degrees +/-8.06 degrees ) but the difference was not significant (t-test, p = 0.063). A statistically significant difference in cranial base shape existed between the two sexes, but the results also demonstrated a major overlap between the female and male shapes. In the light of the observed results, we confirm the lack of accuracy reported when using the lateral angle method to determine sex and we hypothesise that it may be explained by a lack of sexual dimorphism of the cranial base in terms of shape. PMID- 27000031 TI - Glomerulopathy in patients with distal duplication of chromosome 6p. AB - BACKGROUND: Duplication of the distal part of chromosome 6p is a rare genetic syndrome. Renal involvement has been reported in the majority of patients, including a wide range of congenital abnormalities of kidney and urinary tract and, occasionally, a proteinuric glomerulopathy. CASE PRESENTATION: Here, we report a 13-year-old girl with 6p25.3p22.1 duplication who presented with proteinuria in infancy, was later diagnosed as focal segmental glomerulosclerosis, progressed to end-stage renal disease and was successfully transplanted. CONCLUSION: A systematic literature review suggests that 15-20 % of individuals with distal 6p duplication develop progressive proteinuric glomerulopathy. Monitoring of kidney function should be recommended in all cases. PMID- 27000033 TI - Indian medical council should be scrapped, says parliamentary committee. PMID- 27000034 TI - Feasibility, acceptability and impact of integrating malaria rapid diagnostic tests and pre-referral rectal artesunate into the integrated community case management programme. A pilot study in Mchinji district, Malawi. AB - BACKGROUND: The World Health Organization recommends that persons of all ages suspected of malaria should receive a parasitological confirmation of malaria by use of malaria rapid diagnostic test (RDT) at community level, and that rectal artesunate should be used as a pre-referral treatment for severe malaria to rapidly reduce parasitaemia. This paper reports on findings from a pilot study that assessed the feasibility, acceptability and effects of integrating RDTs and pre-referral rectal artesunate into the integrated Community Case Management programme in Malawi. METHODS: This study used mixed methods to collect information for this survey. Pre- and post-intervention, cross-sectional, household surveys were carried out. A review of integrated community case management reports, including supervision checklists was conducted. Quantitative data were collected in tablets running on open data kit software, and then data were transferred to STATA version 12 for analysis. For key indicators, proportions were calculated at 95% confidence intervals. Qualitative data were recorded onto digital recorders, translated into English and transcribed for analysis. RESULTS: Out of 86 observed RDT performances, a total of 83 (97%) were performed correctly with a proper disposal of sharps and biohazard wastes. Only two (2%) febrile children who had an RDT negative result were treated with artemether-lumefantrine, contrary to malaria treatment guidelines. Utilization of community health workers (CHWs) as a first source of care increased from (33.9%) (95% CI; 25.5-42.3) at baseline to (89.7%) (95% CI; 83.5-95.5) at end line in the intervention villages. There was a corresponding decrease in the proportion of caregivers that first sought care from informal sources from 12.9% (95% CI; 6.9 18.9) to 1.9% (95% CI; 0.9-4.4) in the intervention villages. Acceptability of the use of RDTs and pre-referral rectal artesunate at the community level was relatively high. CONCLUSION: Integration of RDTs and pre-referral rectal at artesunate community level is both feasible and acceptable. The strategy has the potential to increase and improve utilization of child health services at community level. However, this depends on the CHWs' skills and their availability in remote areas. PMID- 27000035 TI - Health literacy and the determinants of obesity: a population-based survey of sixth grade school children in Taiwan. AB - BACKGROUND: Health literacy has become an important health policy and health promotion agenda item in recent years. It had been seen as a means to reduce health disparities and a critical empowerment strategy to increase people's control over their health. So far, most of health literacy studies mainly focus on adults with few studies investigating associations between child health literacy and health status. This study aimed to investigate the association between health literacy and body weight in Taiwan's sixth grade school children. METHODS: Using a population-based survey, 162,209 sixth grade (11-12 years old) school children were assessed. The response rate at school level was 83%, with 70% of all students completing the survey. The Taiwan child health literacy assessment tool was applied and information on sex, ethnicity, self-reported health, and health behaviors were also collected. BMI was used to classify the children as underweight, normal, overweight, or obese. A multinomial logit model with robust estimation was used to explore associations between health literacy and the body weight with an adjustment for covariates. RESULTS: The sample consisted of 48.9% girls, 3.8% were indigenous and the mean BMI was 19.55 (SD = 3.93). About 6% of children self-reported bad or very bad health. The mean child health literacy score was 24.03 (SD = 6.12, scale range from 0 to 32). The overall proportion of obese children was 15.2%. Children in the highest health literacy quartile were less likely to be obese (12.4%) compared with the lowest quartile (17.4%). After controlling for gender, ethnicity, self-rated health, and health behaviors, children with higher health literacy were less likely to be obese (Relative Risk Ratio (RRR) = 0.94, p < 0.001) and underweight (RRR = 0.83, p < 0.001). Those who did not have regular physical activity, or had sugar sweetened beverage intake (RRR > 1.10, p < 0.0001) were more likely to report being overweight or obese. CONCLUSIONS: This study demonstrates strong links between health literacy and obesity, even after adjusting for key potential confounders, and provides new insights into potential intervention points in school education for obesity prevention. Systematic approaches to integrating a health literacy curriculum into schools may mitigate the growing burden of disease due to obesity. PMID- 27000036 TI - Cognitive rehabilitation for Parkinson's disease dementia: a study protocol for a pilot randomised controlled trial. AB - BACKGROUND: There is growing interest in developing non-pharmacological treatments to address the cognitive deficits apparent in Parkinson's disease dementia and dementia with Lewy bodies. Cognitive rehabilitation is a goal oriented behavioural intervention which focuses on improving everyday functioning through management of cognitive difficulties; it has been shown to be effective in Alzheimer's disease. To date, no studies have assessed its potential efficacy for addressing the impact of cognitive impairment in people with Parkinson's disease or dementia with Lewy bodies. METHODS/DESIGN: Participants (n = 45) will be recruited from movement disorders, care for the elderly and memory clinics. Inclusion criteria include: a diagnosis of Parkinson's disease, Parkinson's disease dementia or dementia with Lewy bodies according to consensus criteria and an Addenbrooke's Cognitive Examination - III score of <= 82. Exclusion criteria include: a diagnosis of any other significant neurological condition; major psychiatric disorder, including depression, which is not related to the patient's Parkinson's disease and unstable medication use for their physical or cognitive symptoms. A single-blind pilot randomised controlled trial, with concurrent economic evaluation, will compare the relative efficacy of cognitive rehabilitation with that of two control conditions. Following a goal-setting interview, the participants will be randomised to one of the three study arms: cognitive rehabilitation (eight weekly sessions), relaxation therapy (eight weekly sessions) or treatment as usual. Randomisation and treatment group allocation will be carried out by a clinical trials unit using a dynamic adaptive sequential randomisation algorithm. The primary outcomes are patients' perceived goal attainment at a 2-months post-intervention assessment and a 6-months follow up. Secondary outcomes include patients' objective cognitive performance (on tests of memory and executive function) and satisfaction with goal attainment, carers' perception of patients' goal attainment and patients' and carers' health status and psychosocial well-being, measured at the same time points. Cost effectiveness will be examined to explore the design of a larger cost effectiveness analysis alongside a full trial. DISCUSSION: This pilot study will evaluate the application of cognitive rehabilitation for the management of cognitive difficulties associated with Parkinson's disease dementia and dementia with Lewy bodies. The results of the study will inform the design of a fully powered randomised controlled trial. TRIAL REGISTRATION: ISRCTN16584442 DOI 10.1186/ISRCTN16584442 13 April 2015. PMID- 27000037 TI - Tetrodotoxin-sensitive alpha-subunits of voltage-gated sodium channels are relevant for inhibition of cardiac sodium currents by local anesthetics. AB - The sodium channel alpha-subunit (Nav) Nav1.5 is regarded as the most prevalent cardiac sodium channel required for generation of action potentials in cardiomyocytes. Accordingly, Nav1.5 seems to be the main target molecule for local anesthetic (LA)-induced cardiotoxicity. However, recent reports demonstrated functional expression of several "neuronal" Nav's in cardiomyocytes being involved in cardiac contractility and rhythmogenesis. In this study, we examined the relevance of neuronal tetrodotoxin (TTX)-sensitive Nav's for inhibition of cardiac sodium channels by the cardiotoxic LAs ropivacaine and bupivacaine. Effects of LAs on recombinant Nav1.2, 1.3, 1.4, and 1.5 expressed in human embryonic kidney cell line 293 (HEK-293) cells, and on sodium currents in murine, cardiomyocytes were investigated by whole-cell patch clamp recordings. Expression analyses were performed by reverse transcription PCR (RT-PCR). Cultured cardiomyocytes from neonatal mice express messenger RNA (mRNA) for Nav1.2, 1.3, 1.5, 1.8, and 1.9 and generate TTX-sensitive sodium currents. Tonic and use-dependent block of sodium currents in cardiomyocytes by ropivacaine and bupivacaine were enhanced by 200 nM TTX. Inhibition of recombinant Nav1.5 channels was similar to that of TTX-resistant currents in cardiomyocytes but stronger as compared to inhibition of total sodium current in cardiomyocytes. Recombinant Nav1.2, 1.3, 1.4, and 1.5 channels displayed significant differences in regard to use-dependent block by ropivacaine. Finally, bupivacaine blocked sodium currents in cardiomyocytes as well as recombinant Nav1.5 currents significantly stronger in comparison to ropivacaine. Our data demonstrate for the first time that cardiac TTX-sensitive sodium channels are relevant for inhibition of cardiac sodium currents by LAs. PMID- 27000038 TI - Sedation in the Endoscopy Suite. AB - OPINION STATEMENT: Sedation practices in the endoscopy suite have changed dramatically in the decades since the introduction of routine colonoscopy and esophagogastroduodenoscopy (EGD). Patients initially received moderate sedation (or even no sedation), but now frequently receive monitored anesthesia care (MAC). This significant shift has introduced anesthesiologists to the endoscopy suite along with new sedative medications and safety concerns. Appreciating the ramifications of this change requires an understanding of sedation depth, patient selection, drug use, sedation delivery, patient monitoring, recovery from sedation, and patient outcomes. Furthermore, the changing landscape of healthcare quality and reimbursement challenges us to provide the best possible care for our patients in the most economical way possible. The endoscopy suite is a unique sedation environment, and it is the purpose of this article to review those elements that contribute to a uniquely demanding work environment. PMID- 27000039 TI - Exploring Pathways Between HIV+ Status and Excellent Overall Health Among Kenyan Women: Family Functioning, Meaningfulness of Life, Seroconcordance, Social Support and Considering the Need for Integrated Care. AB - As people living with HIV/AIDS (PLWHA) live longer, and HIV incidence declines, health systems are transitioning from vertical-only care delivery to horizontal integration with social and other services. This is essential to responding to the chronic nature of the disease, and health systems must respond to full breadth of socio-economic conditions facing PLWHA. We use excellent self-rated health as a referent, and assess the role of non-biomedical conditions in mediating HIV+ status and excellent overall health among a large community sample of Kenyan women. After controlling for age and wealth, we found significant mediation by social support, partner HIV status, meaningfulness of life, family functioning, food sufficiency, and monthly income. If the goal of health systems is to help all people attain the highest level of health, integrating vertical HIV services with socio-economic support and empowerment may be required. Further investigation of the relative contribution of social support, family functioning, food and financial sufficiency should be conducted longitudinally, ideally in collaboration with HIV clinical services. PMID- 27000040 TI - Adverse Childhood Experiences and Use of Cigarettes and Smokeless Tobacco Products. AB - Adverse childhood experiences (ACEs) have been linked to increased use of tobacco products later in life. However, studies to date have ignored smokeless tobacco products. To address this, data from the 2011 Behavioral Risk Factor Surveillance System, which interviewed adults 18 years and over (N = 102,716) were analyzed. Logistic regression models were fit to estimate odds ratios of ever smoking, current smoking and current smokeless tobacco use in relation to ACEs. Results showed that less than 4 % of respondents currently used smokeless tobacco products, while 44.95 and 18.57 % reported ever and current smoking, respectively. Physical abuse (OR 1.40; 95 % CI 1.14, 1.72), emotional abuse (OR 1.41; 95 % CI 1.19, 1.67), sexual abuse (OR 0.70; 95 % CI 0.51, 0.95), living with a drug user (OR 1.50; 95 % CI 1.17, 1.93), living with someone who was jailed (OR 1.50; 95 % CI 1.11, 2.02) and having parents who were separated or divorced (OR 1.31; 95 % CI 1.09, 1.57) were associated with smokeless tobacco use in unadjusted models. After accounting for confounders, physical abuse (OR 1.43; 95 % CI 1.16, 1.78), emotional abuse (OR 1.32; 95 % CI 1.10, 1.57), living with a problem drinker (OR 1.30; 95 % CI 1.08, 1.58), living with a drug user (OR 1.31; 95 % CI 1.00, 1.72) and living with adults who treated each other violently (OR 1.30; 95 % CI 1.05, 1.62) were associated with smokeless tobacco use. Living with someone who was mentally ill (OR 0.70; 95 % CI 0.53, 0.92) was associated with smokeless tobacco use after accounting for confounders and all ACEs. Results indicated that some childhood adversities are associated with use of smokeless tobacco products. Special attention is needed to prevent tobacco use of different types among those experiencing ACEs. PMID- 27000041 TI - Characteristics of Community Newspaper Coverage of Tobacco Control and Its Relationship to the Passage of Tobacco Ordinances. AB - To answer the call for more systematic surveillance, analysis and evaluation of tobacco news coverage, a 6-year content analysis of newspaper stories from Missouri was conducted to evaluate the presence of public health facts and characteristics of stories framed for or against tobacco control. The method was a content analysis of all Missouri newspapers (N = 381) from September 2006 to November 2011 for a total sample of 4711. Results were connected to the larger, societal context within which newspaper stories reside, i.e., towns that passed or did not pass a smoke-free ordinance during the project intervention. Results showed the majority of news stories were about tobacco control, which were mostly written at the local level, were episodic, and carried a positive slant toward tobacco control. However, there were more negative than positive headlines, and more negative editorials than non-editorials. Tobacco control stories used fewer public health facts than non-tobacco control stories. Towns with existing smoke free ordinances had more tobacco control stories, and towns without smoke-free ordinances had fewer tobacco control stories and more non-tobacco control stories, suggesting a connection between news media coverage and the passage of smoke-free policies. We conclude that the tobacco industry may have had success in impacting news stories in no-ordinance cities by diverting attention from tobacco control to secondary topics, such as youth smoking, which meant stories had fewer public health facts and fewer positive health benefits in towns that may have needed these details most. PMID- 27000042 TI - Update on Metastatic Uveal Melanoma: Progress and Challenges. AB - Uveal melanoma is a rare and biologically distinct type of melanoma arising from melanocytes of the uveal tract; it is associated with a poor prognosis due to the lack of effective systemic treatments. Recent advances in the pathogenesis of uveal melanoma offer an unprecedented opportunity for investigation of new compounds. The purpose of this paper was to analyse the existing evidence about the molecular pathology and immunobiology of advanced uveal melanoma and their implications for systemic targeted therapies and immunotherapy, as well as to discuss future treatment strategies based on data provided by clinical and translational research studies. PMID- 27000043 TI - Sparse regression models for unraveling group and individual associations in eQTL mapping. AB - BACKGROUND: As a promising tool for dissecting the genetic basis of common diseases, expression quantitative trait loci (eQTL) study has attracted increasing research interest. Traditional eQTL methods focus on testing the associations between individual single-nucleotide polymorphisms (SNPs) and gene expression traits. A major drawback of this approach is that it cannot model the joint effect of a set of SNPs on a set of genes, which may correspond to biological pathways. RESULTS: To alleviate this limitation, in this paper, we propose geQTL, a sparse regression method that can detect both group-wise and individual associations between SNPs and expression traits. geQTL can also correct the effects of potential confounders. Our method employs computationally efficient technique, thus it is able to fulfill large scale studies. Moreover, our method can automatically infer the proper number of group-wise associations. We perform extensive experiments on both simulated datasets and yeast datasets to demonstrate the effectiveness and efficiency of the proposed method. The results show that geQTL can effectively detect both individual and group-wise signals and outperforms the state-of-the-arts by a large margin. CONCLUSIONS: This paper well illustrates that decoupling individual and group-wise associations for association mapping is able to improve eQTL mapping accuracy, and inferring individual and group-wise associations. PMID- 27000044 TI - An update on drug-induced arthritis. AB - A large and heterogeneous group of drugs can cause drug-induced arthritis. No single pathogenetic mechanism or drug class unifies these diverse culprits. Recognizing that joint symptoms may, in fact, be drug-related not only saves time and unnecessary investigations but can also prevent needless suffering and morbidity due to late recognition of a drug-induced arthritic condition. The extent of drug-induced arthritis is variable and ranges from minor short-lived and reversible arthralgia to a prolonged and occasionally destructive arthritis. The onset of arthritis due to various medications in relation to the timing of drug initiation is also variable and may range from a few days to several months. PMID- 27000045 TI - Serum biomarkers for the diagnosis and monitoring of chronic recurrent multifocal osteomyelitis (CRMO). AB - Chronic recurrent multifocal osteomyelitis (CRMO), the most severe form of chronic nonbacterial osteomyelitis, is an autoinflammatory bone disorder. A timely diagnosis and treatment initiation is complicated by the absence of widely accepted diagnostic criteria and an incomplete pathophysiological understanding. The aim of this study was to determine biomarkers for the diagnosis and follow-up of CRMO. Serum of 56 CRMO patients was collected at the time of diagnosis. As controls, sera from treatment-naive age-matched patients with Crohn's disease (N = 62) or JIA (N = 28) as well as healthy individuals (N = 62) were collected. Multiplex analysis of 25 inflammation markers was performed. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests, canonical discriminant analysis, and mixed model variance analysis. Mostly monocyte-derived serum proteins were detectable and differed significantly between groups: IL-1RA, IL-2R, IL-6, IL-12, eotaxin, MCP-1, MIP-1b, RANTES. Multicomponent discriminant analysis allowed for the definition of algorithms differentiating between CRMO, Crohn's disease, and healthy controls. Persistently high levels of MCP-1, IL-12, sIL-2R correlated with incomplete remission in follow-up samples from CRMO patients. Discrimination algorithms allow differentiation between patients with CRMO or Crohn's disease, and healthy individuals. IL-12, MCP-1, and sIL-2R can act as markers for treatment response. Though confirmation of our findings in larger multiethnical cohorts is warranted, they may prove valuable to differentiate between otherwise healthy individuals or Crohn's disease patients with "bone pain" and CRMO patients. The elevation of mainly monocyte-derived pro inflammatory serum proteins supports the hypothesis of pro-inflammatory monocyte/macrophages driving inflammation in CRMO. PMID- 27000046 TI - Comparative efficacy and tolerability of duloxetine, pregabalin, and milnacipran for the treatment of fibromyalgia: a Bayesian network meta-analysis of randomized controlled trials. AB - The aim of this study was to assess the relative efficacy and tolerability of duloxetine, pregabalin, and milnacipran at the recommended doses in patients with fibromyalgia. Randomized controlled trials (RCTs) examining the efficacy and safety of duloxetine 60 mg, pregabalin 300 mg, pregabalin 150 mg, milnacipran 200 mg, and milnacipran 100 mg compared to placebo in patients with fibromyalgia were included in this Bayesian network meta-analysis. Nine RCTs including 5140 patients met the inclusion criteria. The proportion of patients with >30 % improvement from baseline in pain was significantly higher in the duloxetine 60 mg, pregabalin 300 mg, milnacipran 100 mg, and milnacipran 200 mg groups than in the placebo group [pairwise odds ratio (OR) 2.33, 95 % credible interval (CrI) 1.50-3.67; OR 1.68, 95 % CrI 1.25-2.28; OR 1.62, 95 % CrI 1.16-2.25; and OR 1.61; 95 % CrI 1.15-2.24, respectively]. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that duloxetine 60 mg had the highest probability of being the best treatment for achieving the response level (SUCRA = 0.9431), followed by pregabalin 300 mg (SUCRA = 0.6300), milnacipran 100 mg (SUCRA = 0.5680), milnacipran 200 mg (SUCRA = 0.5617), pregabalin 150 mg (SUCRA = 0.2392), and placebo (SUCRA = 0.0580). The risk of withdrawal due to adverse events was lower in the placebo group than in the pregabalin 300 mg, duloxetine 60 mg, milnacipran 100 mg, and milnacipran 200 mg groups. However, there was no significant difference in the efficacy and tolerability between the medications at the recommended doses. Duloxetine 60 mg, pregabalin 300 mg, milnacipran 100 mg, and milnacipran 200 mg were more efficacious than placebo. However, there was no significant difference in the efficacy and tolerability between the medications at the recommended doses. PMID- 27000047 TI - Live and inactivated Salmonella enterica serovar Typhimurium stimulate similar but distinct transcriptome profiles in bovine macrophages and dendritic cells. AB - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of gastroenteritis in cattle and humans. Dendritic cells (DC) and macrophages (Mo) are major players in early immunity to Salmonella, and their response could influence the course of infection. Therefore, the global transcriptional response of bovine monocyte-derived DC and Mo to stimulation with live and inactivated S. Typhimurium was compared. Both cell types mount a major response 2 h post infection, with a core common response conserved across cell-type and stimuli. However, three of the most affected pathways; inflammatory response, regulation of transcription and regulation of programmed cell death, exhibited cell-type and stimuli-specific differences. The expression of a subset of genes associated with these pathways was investigated further. The inflammatory response was greater in Mo than DC, in the number of genes and the enhanced expression of common genes, e.g., interleukin (IL) 1B and IL6, while the opposite pattern was observed with interferon gamma. Furthermore, a large proportion of the investigated genes exhibited stimuli-specific differential expression, e.g., Mediterranean fever. Two-thirds of the investigated transcription factors were significantly differentially expressed in response to live and inactivated Salmonella. Therefore the transcriptional responses of bovine DC and Mo during early S. Typhimurium infection are similar but distinct, potentially due to the overall function of these cell-types. The differences in response of the host cell will influence down-stream events, thus impacting on the subsequent immune response generated during the course of the infection. PMID- 27000049 TI - Palliative chemotherapy: oxymoron or misunderstanding? AB - Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term "palliative chemotherapy" is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy. With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of "end-of-life chemotherapy"-chemotherapy given close to death, which does not improve longevity or symptom control-while optimizing the use of chemotherapy that has true palliative benefits for patients. PMID- 27000048 TI - Distinctiveness as a function of spatial expansion in verbal working memory: comment on Kreitz, Furley, Memmert, and Simons (2015). AB - In a recent study, Kreitz et al. (Psychological Research 79:1034-1041, 2015) reported on a relationship between verbal working memory capacity and visuo spatial attentional breadth. The authors hinted at attentional control to be the major link underlying this relationship. We put forward an alternative explanation by framing it within the context of a recent theory on serial order in memory: verbal item sequences entering in working memory are coded by adding a spatial context that can be derived from reading/writing habits. The observation by Kreitz et al. (Psychological Research 79:1034-1041, 2015) enriches this framework by suggesting that a larger visuo-spatial attentional breadth allows for internal coding of the verbal items in a more (spatially) distinct manner thereby increasing working memory performance. As such, Kreitz et al. (Psychological Research 79:1034-1041, 2015) is the first study revealing a functional link between visuo-spatial attentional breadth and verbal working memory size, which strengthens spatial accounts of serial order coding in working memory. PMID- 27000051 TI - How Cuba eliminated mother-to-child transmission of HIV and syphilis. PMID- 27000050 TI - microRNA-dependent gene regulatory networks in maize leaf senescence. AB - BACKGROUND: Maize grain yield depends mainly on the photosynthetic efficiency of functional leaves, which is controlled by an array of gene networks and other factors, including environmental conditions. MicroRNAs (miRNAs) are small RNA molecules that play important roles in plant developmental regulation. A few senescence-associated miRNAs (SA-miRNAs) have been identified as important participants in regulating leaf senescence by modulating the expression levels of their target genes. RESULTS: To elucidate miRNA roles in leaf senescence and their underlying molecular mechanisms in maize, a stay-green line, Yu87-1, and an early leaf senescence line, Early leaf senescence-1 (ELS-1), were selected as experimental materials for the differential expression of candidate miRNAs. Four small RNA libraries were constructed from ear leaves at 20 and 30 days after pollination and sequenced by Illumina deep sequencing technology. Altogether, 81 miRNAs were detected in both lines. Of these, 16 miRNAs of nine families were differentially expressed between ELS-1 andYu87-1. The phenotypic and chlorophyll content analyses of both lines identified these 16 differentially expressed miRNAs as candidate SA-miRNAs. CONCLUSIONS: In this study, 16 candidate SA-miRNAs of ELS-1 were identified through small RNA deep sequencing technology. Degradome sequencing results indicated that these candidate SA-miRNAs may regulate leaf senescence through their target genes, mainly transcription factors, and potentially control chlorophyll degradation pathways. The results highlight the regulatory roles of miRNAs during leaf senescence in maize. PMID- 27000052 TI - Directed Acyclic Graphs for Oral Disease Research. AB - Directed acyclic graphs (DAGs) are nonparametric graphical tools used to depict causal relations in the epidemiologic assessment of exposure-outcome associations. Although their use in dental research was first advocated in 2002, DAGs have yet to be widely adopted in this field. DAGs help identify threats to causal inference such as confounders, bias due to subject selection, and inappropriate handling of missing data. DAGs can also inform the data analysis strategy based on relations among variables depicted on it. This article uses the example of a study of temporomandibular disorders (TMDs), investigating causal effects of facial injury on subsequent risk of TMD. We illustrate how DAGs can be used to identify 1) potential confounders, 2) mediators and the consequences of attempt to estimate direct causal effects, 3) colliders and the consequences of conditioning on colliders, and 4) variables that are simultaneously mediators and confounders and the consequences of adjustment for such variables. For example, one DAG shows that statistical adjustment for the pressure pain threshold would necessarily bias the causal relation between facial injury and TMD. Finally, we discuss the usefulness of DAGs during study design, subject selection, and choosing variables to be measured in a study. PMID- 27000054 TI - Right heart dilatation: a rare vascular cause. AB - CLINICAL INTRODUCTION: A 17-year-old boy with primary cardiac diagnosis of cor triatriatum, atrial septal defect (ASD) and patent ductus arteriosus (PDA) was referred for a cardiac MRI. He was operated on at 3 months of age with correction of the above-mentioned defects. During follow-up, on echocardiogram, he gradually developed moderate right ventricular dilation with preserved systolic function and a trace of tricuspid regurgitation. The interatrial septum was intact and the left chambers looked normal in size (see online supplementary video 1). Clinically, he was active and asymptomatic with saturations of 99% on air. Consequently, he was referred for an MRI scan to look for possible causes. The images are seen in figure 1. QUESTION: What diagnosis would you suspect from figure 1?Arteriovenous malformationLeft superior vena cavaLevoatriocardinal veinMeandering pulmonary vein. PMID- 27000053 TI - Evolutionary interaction between W/Y chromosome and transposable elements. AB - The W/Y chromosome is unique among chromosomes as it does not recombine in its mature form. The main side effect of cessation of recombination is evolutionary instability and degeneration of the W/Y chromosome, or frequent W/Y chromosome turnovers. Another important feature of W/Y chromosome degeneration is transposable element (TEs) accumulation. Transposon accumulation has been confirmed for all W/Y chromosomes that have been sequenced so far. Models of W/Y chromosome instability include the assemblage of deleterious mutations in protein coding genes, but do not include the influence of transposable elements that are accumulated gradually in the non-recombining genome. The multiple roles of genomic TEs, and the interactions between retrotransposons and genome defense proteins are currently being studied intensively. Small RNAs originating from retrotransposon transcripts appear to be, in some cases, the only mediators of W/Y chromosome function. Based on the review of the most recent publications, we present knowledge on W/Y evolution in relation to retrotransposable element accumulation. PMID- 27000055 TI - Heart transplantation in Fontan patients across Australia and New Zealand. AB - OBJECTIVE: Patients with Fontan physiology may eventually require heart transplantation (HT). We determined the rates and outcomes of HT in a national, population-based multicentre study. METHODS: From 1990 to 2015, 1369 patients underwent the Fontan procedure as recorded in the Australia and New Zealand Fontan Registry. We identified those who underwent HT and analysed their outcomes. We compared rates of HT between two catchment areas. In area 1 (n=721), patients were referred to the national paediatric HT programme or its associated adult programme. In area 2 (n=648), patients were referred to the national paediatric HT programme or one of the other adult HT programmes. RESULTS: Mean follow-up time post-Fontan was 11+/-8 years. Freedom from Fontan failure was 74%+/-3.9% at 20 years. HT was performed in 34 patients. Patients living in area 1 were more likely to have HT (4.0%, 29/721 vs 0.8%, 5/648, p<0.001) with a cumulative proportion of 3.4% vs 0.7% at 10 years and 6.8% vs 1.2% at 20 years (p=0.002). Area 1 patients were more likely to undergo HT (hazard ratio 4.7, 95% CI 1.7 to 13.5, p=0.003) on multivariable regression. Post-HT survival at 1, 5 and 10 years was 91%, 78% and 71%, respectively. Compared with other patients with congenital heart disease (n=87), Fontan patients had similar in-hospital outcomes and long-term survival. CONCLUSIONS: Although HT after the Fontan procedure can be achieved with excellent outcomes, most patients with Fontan failure do not undergo HT. Significant regional differences in rates of HT in Fontan patients exist. PMID- 27000056 TI - Spatial physical activity patterns among primary school children living in neighbourhoods of varying socioeconomic status: a cross-sectional study using accelerometry and Global Positioning System. AB - BACKGROUND: Neighbourhood socioeconomic status (SES) has been shown to be related to health status and overweight independent of individual SES. However, results about the association between neighbourhood SES and physical activity among children are ambiguous. Particularly, it is unknown how socioeconomic factors influence the spatial context of children's moderate-vigorous physical activity (MVPA) and sedentary behaviour (SB). This study aimed to investigate by means of Global Positioning System (GPS) and accelerometry whether locations where children engage in MVPA and SB differ by neighbourhood SES. METHODS: Participants included 83 children aged 7-9 from nine public schools located in a low- and high SES area in Zurich, Switzerland. Children wore an accelerometer and GPS sensor for seven consecutive days. Time-matched accelerometer and GPS data was mapped with a geographic information system and each data point assigned to one of eight activity settings. The amount and proportion of MVPA and SB were calculated for every setting. To investigate differences between the two SES groups, multilevel analyses accounting for the hierarchical structure of the data were conducted. RESULTS: Both SES groups achieved most minutes in MVPA at own school, on streets and at home and recorded the highest proportions of MVPA in recreational facilities, streets and other schools. The highest amounts and proportions of SB were found at home and own school. High-SES children accumulated significantly more minutes in MVPA and SB in parks, sport facilities, other schools and streets, while the low-SES group spent more time in both activities in other places. When taking the total time spent in a setting into account and using the proportion of MVPA or SB, the only differences between the two groups were found at other schools and outside, where the high-SES children showed a significantly higher activity level (p-values <0.001). CONCLUSIONS: Several differences in the spatial activity pattern between children from low- and high-SES neighbourhoods were found, independent of their individual SES. The findings seem to highlight the importance of providing safe streets and access to appropriate types of recreational facilities to reach recommended PA levels. Further policies to reduce SB within home and school environment are needed. PMID- 27000057 TI - Development and evaluation of a test program for Y-site compatibility testing of total parenteral nutrition and intravenous drugs. AB - BACKGROUND: There is no standardized procedure or consensus to which tests should be performed to judge compatibility/incompatibility of intravenous drugs. The purpose of this study was to establish and evaluate a test program of methods suitable for detection of physical incompatibility in Y-site administration of total parenteral nutrition (TPN) and drugs. METHODS: Eight frequently used methods (dynamic light scattering, laser diffraction, light obscuration, turbidimetry, zeta potential, light microscopy, pH-measurements and visual examination using Tyndall beams), were scrutinized to elucidate strengths and weaknesses for compatibility testing. The responses of the methods were tested with samples containing precipitation of calcium phosphate and with heat destabilized TPN emulsions. A selection of drugs (acyclovir, ampicillin, ondansetron and paracetamol) was mixed with 3-in-1 TPN admixtures (Olimel(r) N5E, Kabiven(r) and SmofKabiven(r)) to assess compatibility (i.e. potential precipitates and emulsion stability). The obtained compatibility data was interpreted according to theory and compared to existing compatibility literature to further check the validity of the methods. RESULTS: Light obscuration together with turbidimetry, visual inspection and pH-measurements were able to capture signs of precipitations. For the analysis of emulsion stability, light obscuration and estimation of percent droplets above 5 MUm (PFAT5) seemed to be the most sensitive method; however laser diffraction and monitoring changes in pH might be a useful support. Samples should always be compared to unmixed controls to reveal changes induced by the mixing. General acceptance criteria are difficult to define, although some limits are suggested based on current experience. The experimental compatibility data was supported by scattered reports in literature, further confirming the suitability of the test program. However, conflicting data are common, which complicates the comparison to existing literature. CONCLUSIONS: Testing of these complex blends should be based on a combination of several methods and accompanied by theoretical considerations. PMID- 27000058 TI - An Ecological Momentary Intervention for weight loss and healthy eating via smartphone and Internet: study protocol for a randomised controlled trial. AB - BACKGROUND: Long-term weight loss maintenance is difficult to achieve. Effectiveness of obesity interventions could be increased by providing extended treatment, and by focusing on person-environment interactions. Ecological Momentary Intervention (EMI) can account for these two factors by allowing an indefinite extension of a treatment protocol in everyday life. EMI relies on observations in daily life to intervene by providing appropriate in-the-moment treatment. The Think Slim intervention is an EMI based on the principles of cognitive behavioural therapy (CBT), and its effectiveness will be investigated in the current study. METHODS: A randomised controlled trial (RCT) will be conducted. At least 134 overweight adults (body mass index (BMI) above 25 kg/m(2)) will be randomly assigned to an 8-week immediate intervention group (Diet + Think Slim intervention, n = 67) or to an 8-week diet-only control group (followed by the Think Slim intervention, n = 67). The Think Slim intervention consists of (1) an app-based EMI that estimates and intervenes when people are likely to overeat, based on Ecological Momentary Assessment data, and (2) ten online computerised CBT sessions which work in conjunction with an EMI module in the app. The primary outcome is BMI. Secondary outcomes include (1) scores on self-report questionnaires for dysfunctional thinking, eating styles, eating disorder pathology, general psychological symptomatology, and self-esteem, and (2) eating patterns, investigated via network analysis. Primary and secondary outcomes will be obtained at pre- and post-intervention measurements, and at 3- and 12-month follow-up measurements. DISCUSSION: This is the first EMI aimed at treating obesity via a cognitive approach, provided via a smartphone app and the Internet, in the context of an RCT. TRIAL REGISTRATION: This trial has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR5473 ; registration date: 26 October 2015). PMID- 27000059 TI - Integration of Inhibition Kinetics and Molecular Dynamics Simulations: A Urea Mediated Folding Study on Acetaldehyde Dehydrogenase 1. AB - Understanding the mechanism of acetaldehyde dehydrogenase 1 (ALDH1) folding is important because this enzyme is directly involved in several types of cancers and other diseases. We investigated the urea-mediated unfolding of ALDH1 by integrating kinetic inhibition studies with computational molecular dynamics (MD) simulations. Conformational changes in the enzyme structure were also analyzed using intrinsic and 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence measurements. Kinetic studies revealed that the direct binding of urea to ALDH1 induces inactivation of ALDH1 in a manner of mixed-type inhibition. Tertiary structural changes associated with regional hydrophobic exposure of the active site were observed. The urea binding regions on ALDH1 were predicted by docking simulations and were partly shared with active site residues of ALDH1 and with interface residues of the oligomerization domain for tetramer formation. The docking results suggest that urea prevents formation of the ALDH1 normal shape for the tetramer state as well as entrance of the substrate into the active site. Our study provides insight into the structural changes that accompany urea mediated unfolding of ALDH1 and the catalytic role associated with conformational changes. PMID- 27000060 TI - Efficient Secretory Overexpression of Endoinulinase in Escherichia coli and the Production of Inulooligosaccharides. AB - Endoinulinase production was achieved by heteroexpression of endoinulinase encoding gene from Aspergillus ficuum which is an eukaryotic organism in Escherichia coli BL21 (DE3). Further analysis demonstrated that the native signal peptide existed in inu2 gene lowered the enzyme expression level. To realize extracellular accumulation of target protein and improve its expression level, native signal peptide was substituted with pelB, ompC, and pelB fusing with the native signal peptides; then, the effects on endoinulinase production were investigated. As a result, E. coli A606-3, with replacement of pelB as its signal peptide, showed the highest endoinulinase enzyme activity (75.22 U/mg). Also, it suggested that eukaryotic signal peptides have an inhibition on enzyme expression in prokaryotic organism. Moreover, the condition for inulooligosaccharide (IOS) production from inulin was optimized, and an IOS yield of 94.41 % was achieved under the condition of 15 % (w/v) inulin, purified endoinulinase dosage of 5 U/g inulin, 55 degrees C, and pH 4.6 for 24 h. The major products of hydrolysis of inulin were identified as DP3 to DP7. PMID- 27000062 TI - Erratum to: The Efficacy of Perindopril/Amlodipine in Reaching Blood Pressure Targets: Results of the CONTROL Study. PMID- 27000061 TI - Cost-Minimisation Analysis of Paliperidone Palmitate Long-Acting Treatment versus Risperidone Long-Acting Treatment for Schizophrenia in Spain. AB - BACKGROUND AND OBJECTIVE: Long-acting formulations for paliperidone (PPLAT) and risperidone (RLAT) are effective second-generation antipsychotics. This study aimed to compare treatment costs between PPLAT and RLAT in schizophrenia patients. METHODS: A cost-minimization analysis was performed from the perspective of the Spanish National Healthcare System (NHS), in line with the approach accepted by the Scottish Medicine Consortium evaluation. Only direct health costs (?, 2015) were included, i.e. medication (including oral antipsychotic drug supplementation), hospitalization and cost of administration in the community. Two time horizons were used: 1 year (to compare initiation treatment) and 2 years (to compare maintenance treatment). Base-case considered the following assumptions: setting for treatment initiation (50 % hospital and 50 % community); 50 % of patients initiating from a long-acting treatment and 50 % from an oral antipsychotic; no reduction in the length of stay. One-way sensitivity analyses (SA) were performed. RESULTS: The estimated costs/patient were ?7698 (PPLAT) and ?8168 (RLAT) for the first year, and ?4314 (PPLAT) and ?5003 (RLAT) for the second year. Cost savings related to PPLAT therapy were ?470 and ?689 for first and second year, respectively. SA results confirmed the robustness of the model results, even in the most conservative scenarios: (1) if 100 % of patients initiate treatment in hospital, the savings could be ?454 per patient; (2) if 100 % of patients initiate treatment from an oral antipsychotic, the savings could be ?277 per patient/year; and (3) if PPLAT could not reduce the length of stay by approximately one-third, as some studies indicate, the savings could be ?470 per patient/year. CONCLUSIONS: The use of PPLAT instead of RLAT could be a cost-saving strategy for the Spanish NHS. PMID- 27000063 TI - BHV-1 induced oxidative stress contributes to mitochondrial dysfunction in MDBK cells. AB - The levels of cellular reactive oxygen species (ROS) and ATP as well as the mitochondrial membrane potential (MMP) in response to bovine herpesvirus 1 (BHV 1) infection of MDBK cells were measured, respectively. BHV-1 infection increased ROS production which depended on viral entry, and de novo protein expression and/or DNA replication. Vice versa, excessive ROS was required for efficient viral replication. Levels of both ATP and MMP were significantly decreased after BHV-1 infection. Interestingly, the loss of MMP was ameliorated by ROS depression. Collectively, ROS dependent mitochondrial damage and ultimately disruption of energy metabolism (ATP depletion) are a potential pathogenic mechanism for BHV-1 infection. PMID- 27000064 TI - Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4. AB - Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2 receptor EP4 Notably, EP4 also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP4 and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP4 antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP4 receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability. PMID- 27000065 TI - Mitochondrial Pathology and Glycolytic Shift during Proximal Tubule Atrophy after Ischemic AKI. AB - During recovery by regeneration after AKI, proximal tubule cells can fail to redifferentiate, undergo premature growth arrest, and become atrophic. The atrophic tubules display pathologically persistent signaling increases that trigger production of profibrotic peptides, proliferation of interstitial fibroblasts, and fibrosis. We studied proximal tubules after ischemia-reperfusion injury (IRI) to characterize possible mitochondrial pathologies and alterations of critical enzymes that govern energy metabolism. In rat kidneys, tubules undergoing atrophy late after IRI but not normally recovering tubules showed greatly reduced mitochondrial number, with rounded profiles, and large autophagolysosomes. Studies after IRI of kidneys in mice, done in parallel, showed large scale loss of the oxidant-sensitive mitochondrial protein Mpv17L. Renal expression of hypoxia markers also increased after IRI. During early and late reperfusion after IRI, kidneys exhibited increased lactate and pyruvate content and hexokinase activity, which are indicators of glycolysis. Furthermore, normally regenerating tubules as well as tubules undergoing atrophy exhibited increased glycolytic enzyme expression and inhibitory phosphorylation of pyruvate dehydrogenase. TGF-beta antagonism prevented these effects. Our data show that the metabolic switch occurred early during regeneration after injury and was reversed during normal tubule recovery but persisted and became progressively more severe in tubule cells that failed to redifferentiate. In conclusion, irreversibility of the metabolic switch, taking place in the context of hypoxia, high TGF-beta signaling and depletion of mitochondria characterizes the development of atrophy in proximal tubule cells and may contribute to the renal pathology after AKI. PMID- 27000066 TI - T1 mapping of the mouse brain following fractionated manganese administration using MP2RAGE. AB - With the increasing development of transgenic mouse models of neurodegenerative diseases allowing improved understanding of the underlying mechanisms of these disorders, robust quantitative mapping techniques are also needed in rodents. MP2RAGE has shown great potential for structural imaging in humans at high fields. In the present work, MP2RAGE was successfully implemented at 9.4T and 14.1T. Following fractionated injections of MnCl2, MP2RAGE images were acquired allowing simultaneous depiction and T1 mapping of structures in the mouse brain at both fields. In addition, T1 maps demonstrated significant T1 shortenings in different structures of the mouse brain (p < 0.0008 at 9.4T, p < 0.000001 at 14.1T). T1 values recovered to the levels of saline-injected animals 1 month after the last injection except in the pituitary gland. We believe that MP2RAGE represents an important prospective translational tool for further structural MRI. PMID- 27000067 TI - A benchmark for microRNA quantification algorithms using the OpenArray platform. AB - BACKGROUND: Several techniques have been tailored to the quantification of microRNA expression, including hybridization arrays, quantitative PCR (qPCR), and high-throughput sequencing. Each of these has certain strengths and limitations depending both on the technology itself and the algorithm used to convert raw data into expression estimates. Reliable quantification of microRNA expression is challenging in part due to the relatively low abundance and short length of the miRNAs. While substantial research has been devoted to the development of methods to quantify mRNA expression, relatively little effort has been spent on microRNA expression. RESULTS: In this work, we focus on the Life Technologies TaqMan OpenArray(R) system, a qPCR-based platform to measure microRNA expression. Several algorithms currently exist to estimate expression from the raw amplification data produced by qPCR-based technologies. To assess and compare the performance of these methods, we performed a set of dilution/mixture experiments to create a benchmark data set. We also developed a suite of statistical assessments that evaluate many different aspects of performance: accuracy, precision, titration response, number of complete features, limit of detection, and data quality. The benchmark data and software are freely available via two R/Bioconductor packages, miRcomp and miRcompData. Finally, we demonstrate use of our software by comparing two widely used algorithms and providing assessments for four other algorithms. CONCLUSIONS: Benchmark data sets and software are crucial tools for the assessment and comparison of competing algorithms. We believe that the miRcomp and miRcompData packages will facilitate the development of new methodology for microRNA expression estimation. PMID- 27000068 TI - Zika Virus: An Explosive Pandemic and a New TORCH Agent. PMID- 27000069 TI - How Much Do Formula-Fed Infants Take in the First 2 Days? AB - OBJECTIVE: To document the intake of exclusively formula-fed newborns during the first 2 days of life. METHODS: We enrolled a cohort of 50 healthy newborns >=37 weeks' gestation and documented their daily formula intake until discharge. We surveyed pediatricians regarding their assessment of the intake of formula fed infants. RESULTS: In all, 37 of 50 newborns stayed for at least 48 hours. The mean +/- SD gestational age was 39.5 +/- 0.88 weeks. Mean +/-SD formula intake for the first 48 hours (n = 37) was 57.2 +/- 20.4 mL/kg/d and mean weight loss at 45.7 +/- 8.8 hours, was 2.7% of birth weight. Pediatricians underestimated the amounts taken by these infants. CONCLUSIONS: In the first 2 days, healthy term newborns, fed formula ad lib, consume about 115 mL/kg, about 2 to 3 times as much as breastfed infants, and they lose only 2.7% of their birthweight by 48 hours. Most pediatricians underestimate the intake of formula-fed infants. PMID- 27000071 TI - The use of conventional transcutaneous electrical nerve stimulation in chronic facial myalgia patients. AB - OBJECTIVES: The aim of this study was to evaluate the efficacy of conventional TENS in women affected by chronic facial myalgia. MATERIALS AND METHODS: The study was performed on 49 women affected by chronic facial myalgia randomly allocated in the TENS group (34 women) and the control group (15 women). The subjective level of pain was assessed by the Visual Analogue Scale indicating the mean (VAS MEAN), the maximum (VAS MAX) and the current intensity of pain (VAS NOW). The level of pain at the muscular palpation sites was assessed by the Pericranial Muscle Tenderness Score (PTS) and the Cervical Muscle Tenderness Score (CTS). The TENS therapy lasted for 10 weeks, and data were collected at baseline, after 5, 10, 15 and 25 weeks. The differences between groups before and after treatment were compared with the Mann-Whitney and the Kolmogorov-Smirnov tests. The intra-group differences were compared with the one-way ANOVA test. RESULTS: The results showed that the VAS MEAN, VAS MAX, PTS and CTS were significantly reduced in the TENS group compared to the control group after 10 weeks of TENS (p < 0.05). The intra-group analysis revealed a decreasing tendency of VAS MEAN, VAS MAX, VAS NOW, PTS and CTS in the TENS group in a 25-week period (p < 0.05). CONCLUSIONS: The study demonstrated the efficacy of conventional TENS in patients with chronic facial myalgia and the decrease in both subjective and objective pain. CLINICAL RELEVANCE: Conventional TENS is a safe, non-invasive, easy-to-administer therapy for chronic facial myalgia. PMID- 27000070 TI - Effect of DanQi Pill on PPARalpha, lipid disorders and arachidonic acid pathway in rat model of coronary heart disease. AB - BACKGROUND: Danqi pill (DQP) is one of the most widely prescribed formulas and has been shown to have remarkable protective effect on coronary heart disease (CHD). However, its regulatory effects on lipid metabolism disorders haven't been comprehensively studied so far. We aimed to explore the effects of DQP on Peroxisome Proliferator activated receptors alpha (PPARalpha), lipid uptake transportation-metabolism pathway and arachidonic acid (AA)-mediated inflammation pathway in rats with CHD. METHODS: 80 Sprague-Dawley (SD) Rats were randomly divided into sham group, model group, positive control group and DQP group. Rat model of CHD was induced by ligation of left ventricle anterior descending artery and fed with high fat diet in all but the sham group. Rats in sham group only underwent thoracotomy. After surgery, rats in the positive control and DQP group received daily treatments of pravastatin and DQP respectively. At 28 days after surgery, rats were sacrificed and plasma lipids were evaluated by plasma biochemical detection. Western blot and PCR were applied to evaluate the expressions of PPARalpha, proteins involved in lipid metabolism and AA pathways. RESULTS: Twenty eight days after surgery, dyslipidemia developed in CHD model rats, as illustrated by elevated plasma lipid levels. Expressions of apolipoprotein A-I (ApoA-I), cluster of differentiation 36 (CD36) and fatty acid binding protein (FABP) in the heart tissues of model group were down-regulated compared with those in sham group. Expressions of carnitine palmitoyl transferase I (CPT-1A) and lipoproteinlipase (LPL) were also reduced significantly. In addition, levels of phospholipase A2 (PLA2) and cyclooxygenase 2 (COX-2) were up regulated. Expressions of Nuclear factor-kappaB (NF- kappaB) and signal transducer and activator of transcription 3 (STAT3) also increased. Furthermore, Expression of PPARalpha decreased in the model group. DQP significantly up regulated expressions of ApoA-I and FABP, as well as the expressions of CPT-1A and CD36. In addition, DQP down-regulated expressions of PLA2, COX-2 and NF kappaB in inflammation pathway. Levels of STAT3 and LPL were not affected by DQP treatment. In particular, DQP up-regulated PPARalpha level significantly. CONCLUSIONS: DQP could effectively regulate lipid uptake-transportation metabolism process in CHD model rats, and the effect is achieved mainly by activating ApoA-I-CD36-CPT-1A molecules. Interestingly, DQP can up-regulate expression of PPARalpha significantly. The anti-inflammatory effect of DQP is partly exerted by inhibiting expressions of PLA2-COX2 -NF-kappaB pathway. PMID- 27000072 TI - Evaluation of genetic factors involved in nocturnal electromyographic activity of masticatory muscles in twins. AB - OBJECTIVES: The objectives of this study were to assess sleep bruxism events by directly recording electromyographic activity during sleep and to reveal the relative importance of genetic and environmental factors involved in sleep bruxism in twins. MATERIAL AND METHODS: The subjects consisted of 108 twins (mean age 22.2 +/- 6.4 years). Electromyographic activity of temporalis muscles during sleep was evaluated using a portable automatic sleep bruxism analyzer (Grindcare 3.0, Medotech A/S), and recordings were carried out for at least three consecutive nights. Quantitative genetic statistics based on structural equation modeling was utilized to estimate variance components. RESULTS: Monozygotic twin pair correlation for the number of nocturnal electromyographic activities recorded in this study (r = 0.463, P = 0.009) was higher than dizygotic twin-pair correlation (r = 0.103, P = 0.725). The proportion of total phenotypic variance in the liability of sleep bruxism to attribute to genetic influences, related to the electromyographic activities, was 48 % (95 % CI 17-95 %) and to unique environmental influences was 52 % (95 % CI 28-82 %). CONCLUSIONS: Additive genetic effects may be a contributing factor to the occurrence of nocturnal EMG activity associated with sleep bruxism. CLINICAL RELEVANCE: A greater understanding of the contribution of genetic factors could have beneficial uses, including enhanced accuracy of sleep bruxism diagnosis, management of sleep bruxism, and enhanced estimation of the prognosis for patients suffering from sleep bruxism. In addition, it could be also important to adequately evaluate the environmental factors in patients with sleep bruxism. PMID- 27000074 TI - Stereoselective Pharmacodynamics and Pharmacokinetics of Proton Pump Inhibitors. AB - Proton pump inhibitors (PPIs) are a group of gastric acid suppressing drugs, that are strong and long-lasting inhibitors of the proton pump (referred to as acid pump antagonists). They work by irreversibly blocking the H+/K+ ATPase. PPIs are used to treat peptic ulcer disease, gastroesophageal reflux disease, nonsteroidal anti-inflammatory drug-induced gastrointestinal lesions, and Zollinger-Ellison syndrome. The structure of PPIs are similar, they all have a similar core with a sulphur atom chiral center combined with different substituent groups. In relation to the sulphur atom chiral center, the pharmacodynamics, pharmacokinetics are diverse between the racemates and their stereoisomers, which are mainly observed in the following aspects. In regards to pharmacodynamics, the main features of the similarities and differences involve the duration of drug action and the ability to control nocturnal gastric acid secretion. In regards to pharmacokinetic and metabolic pathways, the similarities and differences are measured by the pharmacokinetic and metabolic parameters. These parameters including time to maximal plasma concentration (Tmax), maximal plasma concentration (Cmax), area under the plasma concentration curve (AUC), bioavailability (F) and elimination half-life (t1/2). Compare to the racemates, the stereoisomer (the R-one or the S-one) exhibited less individual differences and better efficiency in acid secretion control. Nowadays, the main reason for PPI development is not so much in relation to the therapeutic effects of these drugs, but is more in the realm of providing longer duration, faster time of onset and better nocturnal gastric acid secretion control. Structure improvement and development of stereoisomer drugs are the two directions for the new generation PPIs. Esomeprazole, dexlansoprazole, ilaprazole and revaprazan, have recently been developed on these principles. However, due to debates on the necessity and superiority of these new drugs, more validation studies are needed. PMID- 27000073 TI - Live-cell fluorescence imaging to investigate the dynamics of plant cell death during infection by the rice blast fungus Magnaporthe oryzae. AB - BACKGROUND: Plant cell death plays important roles during plant-pathogen interactions. To study pathogen-induced cell death, there is a need for cytological tools that allow determining not only host cell viability, but also cellular events leading to cell death with visualization of pathogen development. Here we describe a live cell imaging method to provide insights into the dynamics of cell death in rice (Oryza sativa). This method uses live-cell confocal microscopy of rice sheath cells mechanically damaged or invaded by fluorescently tagged Magnaporthe oryzae together with fluorescent dyes fluorescein diacetate (FDA) and propidium iodide (PI). FDA stains the cytoplasm of live cells exclusively, thus also visualizing the vacuole, whereas PI stains nuclei of dead cells. RESULTS: We first demonstrated that confocal microscopy of rice leaf sheaths stained with FDA and PI discriminated between live cells and mechanically killed cells. FDA-derived fluorescein was confined to the cytoplasm of live cells, indicating the intact vacuolar and plasma membranes. We also observed previously unreported fluorescein patterns in mechanically damaged cells. These patterns include: (1) homogeneous distribution of fluorescein in the increased area of the cytoplasm due to the shrunken vacuole; (2) the increase of the fluorescein intensity; and (3) containment of the brighter fluorescein signal only in affected cells likely due to closure of plasmodesmata. We refer to these as novel fluorescein patterns in this study. Simultaneous imaging of fluorescently-tagged M. oryzae (red) and FDA staining (green) in rice cells revealed characteristic features of the hemibiotrophic interaction. That is, newly invaded cells are alive but subsequently become dead when the fungus spreads into neighbor cells, and biotrophic interfacial complexes are associated with the host cytoplasm. This also revealed novel fluorescein patterns in invaded cells. Time-lapse imaging suggested that the FDA staining pattern in the infected host cell progressed from typical cytoplasmic localization (live cell with the intact vacuole), to novel patterns (dying cell with closed plasmodesmata with the shrunken or ruptured vacuole), to lack of fluorescence (dead cell). CONCLUSION: We have developed a method to visualize cellular events leading to host cell death during rice blast disease. This method can be used to compare and contrast host cell death associated with disease resistance and susceptibility in rice-M. oryzae and other host-pathogen interactions. PMID- 27000075 TI - The Role of Therapeutic Drugs on Acquired Mitochondrial Toxicity. AB - BACKGROUND: Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms including deafness, neuropathy, myopathy, hyperlactatemia, lactic acidosis, pancreatitis and lipodystrophy, among others, which could even compromise the life of the patient. OBJECTIVES: The aim of this work is to review the potential mitochondrial toxicity derived from drugs used in health care, including anesthetics, antiepileptics, neuroleptics, antidepressants, antivirals, antibiotics, antifungals, antimalarics, antineoplastics, antidiabetics, hypolipemiants, antiarrhythmics, anti-inflammatories and nitric oxide. METHODS: We herein have reviewed data from experimental and clinical studies to document the molecular mitochondrial basis, potential biomarkers and putative clinical symptoms associated to secondary effects of drugs. RESULTS: One hundred and forty five articles were selected and the information was organized by means of the primary target to which pharmacologic drugs were directed. Adverse toxic events were classified depending on the mitochondrial offtarget effect and whether they had been demonstrated in the experimental or clinical setting. CONCLUSIONS: Since treatment of acquired mitochondriopathies remains supportive and therapeutic interventions cannot be avoided, information of molecular and clinical consequences of toxic exposure becomes fundamental to assess riskbenefit imbalance of treatment prescription. Additionally, there is a crucial need to develop less mitochondrial toxic compounds, novel biomarkers to follow up mitochondrial toxicity (or implement those already proposed) and new approaches to prevent or revert unintended mitochondrial damage. PMID- 27000076 TI - Valproic Acid Metabolism and its Consequences on Sexual Functions. AB - BACKGROUND: Valproic acid (VPA) is a broad spectrum antiepileptic drug (AED) that is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies. Available data suggest that menstrual disorders and certain endocrine manifestations of reproductive system disorders may be more common in women treated with VPA than in those treated with other AEDs. METHODS: A PubMed search for MEDLINE was undertaken to look for studies using the terms "VPA metabolism", "VPA and sexual functions in men", "VPA and sexual functions in women" and "VPA metabolism and endocrine disorders" as key words. The period covered was approximately 20 years. RESULTS: In women, VPA medication is associated with hyperandrogenism, polycystic ovary/polycystic ovarian syndrome, menstrual disorders and ovulatory failure. Men on VPA therapy show abnormalities in androgens blood levels, sperm motility and erectile dysfunctions. VPA negatively affects the release of luteinizing hormone, follicle stimulating hormone and prolactin but also the drug interferes in peripheral endocrine hormones. Its broad inhibitory action on cytochrome and glucuronidation systems can lead to high serum concentration of testosterone, androstenedione and dehydroepiandrosterone sulfate. VPA-dependent obesity and hyperinsulinemia can further contribute to an increase in sexual dysfunctions. CONCLUSIONS: VPA interferes with the endocrine system at multiples levels causing several reproductive and sexual dysfunctions in women and men with epilepsy, especially when administered in pubertal age. Since VPA is a first line AED both in children and adult with epilepsy and long-term medication with this drug is sometimes necessary, it is very important for physicians to implement strict monitoring of patients taking VPA in order to identify these kinds of side effects at an early stage. PMID- 27000077 TI - Yap1 plays a protective role in suppressing free fatty acid-induced apoptosis and promoting beta-cell survival. AB - Mammalian pancreatic beta-cells play a pivotal role in development and glucose homeostasis through the production and secretion of insulin. Functional failure or decrease in beta-cell number leads to type 2 diabetes (T2D). Despite the physiological importance of beta-cells, the viability of beta-cells is often challenged mainly due to its poor ability to adapt to their changing microenvironment. One of the factors that negatively affect beta-cell viability is high concentration of free fatty acids (FFAs) such as palmitate. In this work, we demonstrated that Yes-associated protein (Yap1) is activated when beta-cells are treated with palmitate. Our loss- and gain-of-function analyses using rodent insulinoma cell lines revealed that Yap1 suppresses palmitate-induced apoptosis in beta-cells without regulating their proliferation. We also found that upon palmitate treatment, re-arrangement of F-actin mediates Yap1 activation. Palmitate treatment increases expression of one of the Yap1 target genes, connective tissue growth factor (CTGF). Our gain-of-function analysis with CTGF suggests CTGF may be the downstream factor of Yap1 in the protective mechanism against FFA-induced apoptosis. PMID- 27000079 TI - Strategies for interday appointment scheduling in primary care. AB - When faced with a medical problem, patients contact their primary care physician (PCP) first. Here mainly two types of patient requests occur: non-scheduled patients who are walk-ins without an appointment and scheduled patients with an appointment. Number and position of the scheduled appointments influence waiting times for patients, capacity for treatment and the utilization of PCPs. As the number of patient requests differs significantly between weekdays, the challenge is to match capacity with patient requests and provide as few appointment slots as necessary. In this way, capacity for walk-ins is maximized while overall capacity restrictions are met. Decisions as to the optimal appointment capacity per day on a tactical decision level has gained little attention in the literature. A mixed integer linear model is developed, where the minimum number of appointments scheduled for a weekly profile is determined. We are thus able to give the answer as to how many appointments to offer on each day in a week in order to create a schedule that takes patient preferences as well as PCP preferences into account. Appointment schedules are often influenced by uncertain demands due to the number of urgent patients, interarrivals and service times. Based on an exemplary case study, the advantages of the optimal appointment schedule on different performance criteria are shown by detailed stochastic simulations. PMID- 27000078 TI - MiRNA-203 suppresses tumor cell proliferation, migration and invasion by targeting Slug in gastric cancer. PMID- 27000080 TI - Erratum to: 'Interpersonal psychotherapy for depression and posttraumatic stress disorder among HIV-positive women in Kisumu, Kenya: study protocol for a randomized controlled trial'. PMID- 27000081 TI - Papillary thyroid carcinoma: different clinical behavior among pT3 tumors. AB - pT3 papillary thyroid carcinoma (PTC) can be divided into three subgroups according to the largest diameter >4 cm or evidence of minimal extrathyroidal extension (ETE): A >4 cm, no ETE; B <=4 cm, with ETE; and C >4 cm, with ETE. The aim of this study was to analyze whether these subgroups are clinically different. A retrospective analysis of clinicopathological data of patients with pT3 PTC, with a minimum follow-up of 2 years, at a referral center was conducted. Outcome was evaluated after primary treatment and after 2 and 5 years of follow up. Patients were classified as no evidence of disease (NED), biochemical evidence of disease (BED), and structural evidence of disease (SED) either locoregional (SED-L) or at distance (SED-D). The study patients were classified into three groups as follows: Group A (n = 91), Group B (n = 101), and Group C (n = 23). Most patients were female (80.0 %); mean age at diagnosis was 49.9 +/- 16.5 years. 214 patients underwent total thyroidectomy; 208 patients were treated with (131)I. Median follow-up was 6.0 years. After primary treatment, the condition of NED was significantly different between the groups (A-87.9 %, B-68.3 %, C-43.5 %; p < 0.001). Recurrence rate, either biochemical or structural, was 8.8, 7.2, and 30.0 % in groups A, B, and C, respectively. Clinical status after 2 years anticipated clinical status after 5 years, except for Group B. ETE and tumor size were found to be predictors of disease status after primary treatment and after 2 years. ETE appeared as the strongest predictor of persistence of disease after primary treatment as well as of evidence of disease, either biochemical or structural, after 2 years of follow-up. PMID- 27000082 TI - Risk factors of gestational diabetes mellitus recurrence: a meta-analysis. AB - The literature regarding risk factors for gestational diabetes mellitus (GDM) recurrence is inconsistent. We aimed to assess the effect sizes of risk factors of GDM recurrence. We searched electronic databases (1970-2015) and bibliographies for studies that included women with GDM (index pregnancy) who had a consecutive birth. We compared the risk factors among women with and without GDM recurrence. Differences in variables measured on a continuous scale were estimated using the weighted mean difference (WMD). The standardized mean difference (SMD) was used to rate the pooled effects. For categorical variables, the pooled odds ratio was estimated. Cochran's Q test of heterogeneity was used to choose the model for estimating the pooled effects. Fourteen cross-sectional cohort studies (63 % with sample size >=100) were considered. Women with GDM recurrence were older (by 1.32 years; P < 0.0001), heavier (by 1.82 BMI; P = 0.013), had higher 100-g oral glucose tolerance test (OGTT) levels (Fasting: by 8.42 mg/dl, 1-h: by 13.0 mg/dl, 2-h: by 18.2 mg/dl, 3-h: by 11.3 mg/dl; P < 0.0001 for all) and higher weight gain between pregnancies (by 3.24 kg; P = 0.012). The SMD effect sizes were relatively small (between 0.3 and 0.4), but weight gain between pregnancies had a medium-large effect size (SMD = 0.8). Insulin use, multiparity, and fetal macrosomia were all associated with GDM recurrence (OR 6.3 [95 % CI 3.9-10.2], OR 1.88 [95 % CI 1.09-3.24] and OR 1.63 [95 % CI 1.25-2.13], respectively). GDM recurrence is multifactorial. Stronger risk factors include insulin use, BMI, multiparity, macrosomia, and weight gain between pregnancies. PMID- 27000083 TI - Morning cortisol levels and glucose metabolism parameters in moderate and severe obstructive sleep apnea patients. AB - Obstructive sleep apnea (OSA) has been associated with dysregulation of the hypothalamic-pituitary-adrenal axis and alterations in glucose metabolism with increased risk for type 2 diabetes. The aim of the current study was to compare morning plasma cortisol levels and glucose metabolism parameters between moderate (apnea-hypopnea index (AHI): 15-30 events/h) and severe OSA patients (AHI >30 events/h), with respective controls. A total of 56 male OSA patients, 24 moderate (AHI = 21.1 +/- 5.3) and 32 severe (AHI = 49.7 +/- 18.1), underwent a full-night polysomnography, oral glucose tolerance test (OGTT), and measurement of morning plasma cortisol levels. These groups were compared to 20 matched subjects in a control group. Morning plasma cortisol levels were statistically lower in severe OSA group than in moderate OSA and control groups (303.7 +/- 93.5 vs. 423.9 +/- 145.1 vs. 417.5 +/- 99.8 pmol/L, P < 0.001). Significant negative correlations were found between morning plasma cortisol levels and AHI (r = -0.444, P = 0.002), as well as oxygen desaturation index (r = -0.381, P = 0.011). Fasting plasma glucose (5.0 +/- 0.5 vs. 5.4 +/- 0.7 vs. 4.9 +/- 0.6 mmol/L, P = 0.009) was higher in the severe OSA group compared to moderate OSA and controls. Homeostasis model assessment insulin resistance (HOMA-IR) was higher in the severe OSA group compared to moderate OSA and controls (4.6 +/- 3.7 vs. 2.7 +/- 2.0 and 2.2 +/- 1.8, respectively, P = 0.006). In conclusion, our study showed that morning plasma cortisol levels measured at 8 a.m. were significantly lower in severe OSA patients than those in moderate OSA group and controls. Morning plasma cortisol levels showed a negative correlation with AHI and oxygen desaturation index. Additionally, this study confirmed the evidence of glucose metabolism impairment in moderate and severe OSA patients, with more pronounced effect in the severe OSA patients group. PMID- 27000084 TI - Living in Two Cultures: Chinese Canadians' Perspectives on Health. AB - Chinese people have distinctive perspectives on health and illness that are largely unrecognized in Western society. The purpose of this descriptive study was to develop a profile of Chinese immigrants' beliefs and practices related to diet, mental and social health, and sexual health. A quantitative survey with descriptive and correlational analyses was employed to examine 100 first generation Chinese immigrants living in four urban centres across Canada (Vancouver, Toronto, Halifax, and St. Catharines). Although most Chinese immigrants preferred a Chinese diet, where they resided affected the groceries they bought and the meals they ate. Almost all participants reported their mental health was important to them and most felt comfortable discussing mental health issues with others. However, only a third would see a psychiatrist if they believed they had a mental health problem. Most participants believed social relationships were important for their health. Only a small number of participants, however, preferred making friends with mainstream Caucasian Canadians. More men than women believed sexuality contributed to health and were comfortable talking about sexual health. Chinese immigrants should be encouraged to be more engaged in the larger community in order to fully integrate themselves into Canadian society while still being encouraged to retain their healthy practices. These findings may help educators and practitioners enhance their understandings of Chinese immigrants' perspectives on health and develop culturally competent education and services in health care and health promotion. PMID- 27000085 TI - Cultural and Religious/Spiritual Beliefs and the Impact on Health that Fear to Death has on Gender and Age, Among a Romani Minority Group from Southern Spain. AB - The Romani cultural minority living in Spain has cultural values and beliefs, religious/spiritual expressions and a particular vision of death. The relationship between these aspects and health is unknown. A sample of 150 people responded to a socio-demographic questionnaire and well-being measures of religious/spiritual experience, paranormal beliefs and fear of death. Age, a negative sense of life, fear of the death of others, being a woman and having low paranormal beliefs have a negative impact on health. Results allow for extending the relationships found in the general population to the Romani population as well. The novelty is that, in the latter, paranormal beliefs protect against disease. Additionally, fear of the death of others damages health more than fear of one's own death. These results make sense in the context of the Romani culture and religion. PMID- 27000086 TI - Seroprevalence of circulating Angiostrongylus vasorum antigen and parasite specific antibodies in dogs from Portugal. AB - Angiostrongylus vasorum is a nematode that lives in the pulmonary arteries and right cardiac ventricle of domestic dogs and wild canids. It is increasingly being reported in several European countries and North America. This parasite induces inflammatory verminous pneumonia, causing severe respiratory disease in dogs. In some instances, coagulopathies, neurological signs and even death may occur. Scant data are available regarding the occurrence of A. vasorum in Portugal. Therefore, sera of 906 shelter dogs from North to South mainland Portugal were collected. ELISAs to detect A. vasorum circulating antigen and specific antibodies against this parasite were performed. A total of six dogs [0.66 %, 95 % confidence intervals (CI) 0.24-1.43] were positive for both A. vasorum antigen and antibody detection, indicating an active infection, and 12 dogs (1.32 %, CI 0.68-2.30) were A. vasorum antibody-positive only. Regions with antigen- and antibody-positive animals overlapped and were distributed over nearly all sampled areas in the country. This is the first large-scale ELISA based serological survey for A. vasorum in dogs from Portugal. The endemic occurrence of A. vasorum in dogs from different geographical areas of Portugal is therefore confirmed. PMID- 27000087 TI - Plasmodium delichoni n. sp.: description, molecular characterisation and remarks on the exoerythrocytic merogony, persistence, vectors and transmission. AB - Malaria parasite Plasmodium (Novyella) delichoni n. sp. (Haemosporida, Plasmodiidae) was found in a widespread Eurasian songbird, the common house martin Delichon urbicum (Hirundinidae). It is described based on the morphology of its blood stages and segments of the mitochondrial cytochrome b and apicoplast genes, which can be used for molecular identification of this species. Erythrocytic meronts and gametocytes are strictly nucleophilic, and mature gametocytes possess pigment granules of markedly variable size, including large ones (1 MUm in length). Due to these features, P. delichoni can be readily distinguished from all described species of avian malaria parasites belonging to subgenus Novyella. Additionally, mature erythrocytic merozoites contain a dense clump of chromatin, a rare character in avian malaria parasites. Erythrocytic merogony is asynchronous. Illustrations of blood stages of the new species are given, and phylogenetic analysis identifies DNA lineages closely related to this parasite. Domestic canary Serinus canaria and Eurasian siskin Carduelis spinus were infected after subinoculation of infected blood obtained from the house martin. Parasitemia was long lasting in both these hosts, but it was high (up to 70 %) in Eurasian siskins and low (up to 1 %) in canaries. Mortality was not observed, and histological examination and chromogenic in situ hybridisation did not reveal secondary exoerythrocytic meronts (phanerozoites) in the exposed birds. It is likely that persistence of this infection occurs due to long-lasting parasitemia in avian hosts. Sporogony was abortive in mosquitoes Culex pipiens pipiens form molestus, Culex quinquefasciatus and Aedes aegypti at gametogenesis or ookinete stages. The new species is absent from juvenile birds at breeding sites in Europe, indicating that transmission occurs at African wintering grounds. PMID- 27000088 TI - Molecular detection and characterization of Theileria infection in cattle and yaks from Tibet Plateau Region, China. AB - Theileriosis continues to threaten the livestock industry worldwide, but comprehensive epidemiological surveys for this disease have not been conducted in the Tibet Plateau Region, China. In this study, we screened 154 cattle blood samples from the Tibet Plateau Region (Lhasa, Lhoka, and Tianzhu), China, for detection of Theileria pathogens by polymerase chain reaction (PCR) with species specific primers. The results revealed that the prevalence was 6.9 % (2/29) for Theileria orientalis and 27.6 % (8/29) for Theileria sinensis in Lhasa, 0 % (0/30) for T. orientalis and 26.7 % (8/30) for T. sinensis in Lhoka, and 0 % (0/95) for T. orientalis and 30.5 % (29/95) for T. sinensis in Tianzhu. Interestingly, Theileria luwenshuni, which was a previously reported pathogenic Theileria sp. in sheep and goats, was detected in blood samples from cattle and yaks for the first time, with a prevalence of 10 % (3/30) in Lhoka and 1.1 % (1/95) in Tianzhu. No other Theileria sp. was detected in these samples. T. sinensis and T. orientalis infections were detected in cattle and yaks, and T. luwenshuni was discovered for the first time in cattle and yaks in the Tibet Plateau Region, China. PMID- 27000091 TI - Strategies to Block Bacterial Pathogenesis by Interference with Motility and Chemotaxis. AB - Infections by motile, pathogenic bacteria, such as Campylobacter species, Clostridium species, Escherichia coli, Helicobacter pylori, Listeria monocytogenes, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Salmonella species, Vibrio cholerae, and Yersinia species, represent a severe economic and health problem worldwide. Of special importance in this context is the increasing emergence and spread of multidrug-resistant bacteria. Due to the shortage of effective antibiotics for the treatment of infections caused by multidrug resistant, pathogenic bacteria, the targeting of novel, virulence-relevant factors constitutes a promising, alternative approach. Bacteria have evolved distinct motility structures for movement across surfaces and in aqueous environments. In this review, I will focus on the bacterial flagellum, the associated chemosensory system, and the type-IV pilus as motility devices, which are crucial for bacterial pathogens to reach a preferred site of infection, facilitate biofilm formation, and adhere to surfaces or host cells. Thus, those nanomachines constitute potential targets for the development of novel anti infectives that are urgently needed at a time of spreading antibiotic resistance. Both bacterial flagella and type-IV pili (T4P) are intricate macromolecular complexes made of dozens of different proteins and their motility function relies on the correct spatial and temporal assembly of various substructures. Specific type-III and type-IV secretion systems power the export of substrate proteins of the bacterial flagellum and type-IV pilus, respectively, and are homologous to virulence-associated type-III and type-II secretion systems. Accordingly, bacterial flagella and T4P represent attractive targets for novel antivirulence drugs interfering with synthesis, assembly, and function of these motility structures. PMID- 27000089 TI - Description of Haemoproteus ciconiae sp. nov. (Haemoproteidae, Haemosporida) from the white stork Ciconia ciconia, with remarks on insensitivity of established polymerase chain reaction assays to detect this infection. AB - Haemoproteus ciconiae sp. nov. (Haemosporida, Haemoproteidae) was found in the white stork Ciconia ciconia (Ciconiiformes, Ciconiidae) after spring migration in Lithuania. This organism is illustrated and described based on the morphology of its blood stages. The new species can be readily distinguished from all other haemoproteids parasitizing ciconiiform birds due to the presence of large number (approximately 20 on average) small (<1 MUm) pigment granules in its mature gametocytes. Growing and mature gametocytes of H. ciconiae were readily visible in all blood films (parasitemia of 0.001 %). However, experienced researchers were unable to detect sequences of its mitochondrial cytochrome b (cyt b) or apicoplast genes from the microscopically positive sample by using five established assays for polymerase chain reaction (PCR)-based detection of avian haemosporidian parasites. The white stork cyt b sequence was readily detectable, indicating the well-optimised PCR protocols and the good quality of total DNA in the sample containing the new species. The failure to amplify this parasite DNA indicates insufficient sensitivity of the currently used PCR-based assays in diagnostics of avian haemosporidian infections. We suggest possible explanations of this observation. To minimize number of the false negative PCR reports, we call for the continued use of optical microscopy in parallel with molecular diagnostics in studies of haemosporidian parasites, particularly in wildlife. PMID- 27000092 TI - Physical fitness of overweight and underweight preschool children from southern Poland. AB - SUMMARY: The main aim of this study was to assess differences in the level of physical fitness between children of preschool age with different BMI, as overweight and obesity are an increasing problem even in this age group. The study group consisted of 3,945 children aged 4 to 6 years living in southern Poland. Analysis included the results of body height and weight measurements (from which BMI was calculated) and motor skills tests: sit-and-reach test, standing broad jump and handgrip strength. Children were grouped according to the Obesity Task Force categories. Significant differences in body height were visible (i) between overweight and normal children and (ii) between overweight and underweight children. In terms of body weight and BMI, significant differences existed between all groups. With regard to fitness tests, the greatest differences were observed for handgrip strength and standing broad jump. The sit-and-reach test did not reveal any differences between the groups. The results showed that overall physical fitness was negatively correlated with relative weight; general fitness in overweight children was lower than in normal or underweight children. As it is obvious that physical activity is indispensable even for preschool children, any increase in physical activity could at least partially alleviate the problem of excessive weight and improve the general fitness of children. In the future this would reduce the incidence of diseases related to obesity and a lack of exercise. PMID- 27000093 TI - Successful recanalization for internal carotid artery occlusion with persistent primitive trigeminal artery manifesting only as ischemia of the posterior circulation. AB - BACKGROUND: Internal carotid artery (ICA) occlusion mainly manifests as ischemia of the anterior circulation. There are very few reports of ICA occlusion manifesting as only ischemia of the posterior circulation related to a fetal type posterior communicating artery or other arteries. CASE PRESENTATION: The authors experienced a case of ICA occlusion with persistent primitive trigeminal artery (PPTA) manifesting only as ischemia of the posterior circulation. In this case, the initial NIHSS score was high (35/42 points). Additionally, cross flow of the anterior communicating artery, ICA occlusion and basilar artery (BA) occlusion were represented on the initial head MRA. Therefore, our first impression was a presumptive diagnosis of BA occlusion. Prior head MRI/MRA performed for screening purposes, had incidentally demonstrated a right PPTA. Based on this understanding, we were able to determine the exact angioarchitectural mechanism of the ICA occlusion. Because of the presence of the PPTA, successful recanalization was accomplished expeditiously. CONCLUSION: Although the presence of PPTA is rare and ICA occlusion patients with PPTA is even more unusual, if ICA occlusion and BA occlusion appear simultaneously on MRA, the presence of PPTA should be considered. PMID- 27000094 TI - Behavioural interventions for people living with adult-onset primary dystonia: a systematic review. AB - BACKGROUND: Primary dystonia is a chronic neurological movement disorder that causes abnormal muscle movements. Pain and emotional distress may accompany these physical symptoms. Behavioural interventions are used to help people with long term conditions improve their quality of life. Little is known about behavioural interventions applied to Dystonia. We report a systematic review of studies reporting current evidence of behavioural interventions for people with primary dystonia. METHODS: We did systematic searches of Medline, PsycINFO, AHMED and CINAHL. We assessed the methodological quality of included studies using a risk of bias tool. Any disagreements were resolved by liaising with an independent rater. Physiological outcomes such as dystonia severity and psychological outcomes such as sleep and depression were selected on the basis that primary dystonia causes motor and non-motor symptoms. No time limit was placed on the searches. A narrative synthesis of the results is presented. RESULTS: Of 1798 titles and abstracts screened, 14 full articles were retrieved and inclusion and exclusion criteria applied. Of these a final nine were eligible for the review (N = 73). Only two were Randomised Controlled Trials (RCTs). Using the Movement Disorders Society (MDS) dystonia classification, that was published after this work started, all of the included studies were of idiopathic adult onset focal dystonia without associated features. These included: blepharospasm (eye dystonia) (N = 1), cervical dystonia (neck dystonia) (N = 2), writer's cramp (hand dystonia) (N = 3) and the yips (N = 3). No studies reported on dystonia that affects two or more body regions. Studies reported good adherence and response rates to treatment. Physiological and psychological improvements were noted in all studies at weekly, monthly and yearly follow-ups. Caution should be taken when interpreting the results because of the scarcity of RCTs identified, use of small sample sizes, and inappropriate statistical methods. CONCLUSION: We identified few studies; mainly of poor methodological quality that all studied a focal dystonia. It is not possible to draw firm conclusions. Nevertheless, the data suggests that a combined behavioural therapy approach including relaxation practice for people with idiopathic adult onset focal dystonia merits further investigation. PMID- 27000095 TI - Jalal A. Aliyev (1928-2016): a great scientist, a great teacher and a great human being. AB - Jalal A. Aliyev was a distinguished and respected plant biologist of our time, a great teacher, and great human being. He was a pioneer of photosynthesis research in Azerbaijan. Almost up to the end of his life, he was deeply engaged in research. His work on the productivity of wheat, and biochemistry, genetics and molecular biology of gram (chick pea) are some of his important legacies. He left us on February 1, 2016, but many around the world remember him as he was engaged in international dialog on solving global issues, and in supporting international conferences on ''Photosynthesis Research for Sustainability" in 2011 and 2013. PMID- 27000096 TI - Non redundant functional brain connectivity in schizophrenia. AB - Schizophrenia is considered a disorder of abnormal brain connectivity. Although whole brain maps of averaged bivariate voxel correlations have been successfully applied to study connectivity abnormalities in schizophrenia these maps do not adequately explore the multivariate nature of brain connectivity. Here we adapt a novel method for high-dimensional regression (supervised principal component regression) to estimate brain maps of multivariate non redundant connectivity (NRC) from resting functional Magnetic Resonance Imaging (fMRI) data of 116 patients with schizophrenia and 122 matched controls. Disorder related differences in NRC involved caudate hyper-connectivity and hypo-connectivity of several cortical areas such as the dorsal cingulate, the cuneus and the right postcentral cortex. These abnormalities were coupled with abnormalities in the amplitude of signal fluctuations and, to a minor extent, with differences in the dimensionality of connectivity patterns as quantified by the number of supervised principal components. Second level seed correlation analyses linked the observed abnormalities to an additional set of brain regions relevant to schizophrenia such as the thalamus and the temporal cortex. The non redundant connectivity maps proposed here are a new tool that will complement the information provided by other already available voxel based whole brain connectivity measures. PMID- 27000097 TI - The telephone lifestyle intervention 'Hartcoach' has modest impact on coronary risk factors: A randomised multicentre trial. AB - BACKGROUND: Unhealthy diets and inactivity are still common among patients with cardiovascular diseases. This study evaluates the effects of the telephonic lifestyle intervention 'Hartcoach' on risk factors and self-management in patients with recent coronary events. DESIGN: This was a randomised trial in five Dutch hospitals. METHODS: Patients (18-80 years), less than eight weeks after hospitalisation for acute myocardial infarction or (un)stable angina pectoris were randomised to the Hartcoach-group, who received telephonic coaching every four weeks for a period of six months (in addition to usual care), and a control group receiving usual care only. Simple random allocation was used (without relation to prior assignment). Measurements were taken by research nurses blinded for group allocation. Differences after six months of participation were compared using linear or logistic regression models with treatment-group and baseline score for the outcome under analysis as covariates, resulting in adjusted mean change (b). RESULTS: Altogether 374 patients were randomised (173 Hartcoach + usual care, 201 usual care only). Follow-up was obtained in 331 patients who still participated after six months. Hartcoach had significant favourable effects on body mass index (BMI) (b = -0.32; 95% CI:(-0.63- -0.003)), waist circumference (b = -1.71; 95% CI:(-2.73- -0.70)), physical activity (b = 15.08 (score); 95% CI:(0.13, 30.04)) daily intake of vegetables (b = 13.41; 95% CI:(1.10-25.71)), self-management (b = 0.11; 95% CI:(0.00-0.23)) and anxiety (b = -0.65; 95% CI:( 1.25- -0.06)). Hartcoach slightly increased the total number of risk scores on target (b = 0.45; 95% CI:(0.17-0.73)). CONCLUSIONS: Hartcoach has modest impact on BMI, waist circumference, physical activity, intake of vegetables, self management and anxiety. Therefore, it may be a useful maintenance programme in addition to usual care, to support patients with recent coronary events to improve self-management and reduce risk factors. PMID- 27000098 TI - Does exercise training impact clock genes in patients with coronary artery disease and type 2 diabetes mellitus? AB - BACKGROUND: Recent findings revealed negative effects of deregulated molecular circadian rhythm in coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). Physical exercise training (ET) has been shown to promote anti-diabetic and anti-atherogenic responses in skeletal muscle of these patients, but the role of the circadian clock-machinery remains unknown. This study investigated whether mRNA expression of clock genes in skeletal muscle of CAD and T2DM patients is influenced by physical ET intervention. METHODS: Nineteen patients with CAD and T2DM (age 64 +/- 5 years) were randomised to either six months of ET (four weeks of in-hospital ET followed by a five-month ambulatory programme) or usual care. At the beginning of the study, after four weeks and after six months parameters of metabolic and cardiovascular risk factors, and physical exercise capacity were assessed. Gene expression was measured in skeletal muscle biopsies by quantitative real-time polymerase chain reaction (PCR). RESULTS: A selection of clock genes and associated components (circadian locomoter output cycle kaput protein (CLOCK), period (PER) 1, cryptochrome (CRY) 2 and aminolevulinate-deltA synthase-1 (ALAS1)) was reliably measured and used for further analysis. A time dependent effect in gene expression was observed in CLOCK (p = 0.013) and a significant interaction between time and intervention was observed for ALAS1 (p = 0.032; p = 0.014) as a result of ET. CONCLUSION: This is the first study to analyse clock gene expression in skeletal muscles of patients with CAD and T2DM participating in a long-lasting exercise intervention. ET, as one of the cornerstones in prevention and rehabilitation of CAD and T2DM, exerts no effects on CLOCK genes but meaningful effects on the clock-associated gene ALAS1. PMID- 27000099 TI - Prospective association between a dietary quality index based on a nutrient profiling system and cardiovascular disease risk. AB - BACKGROUND: Public health strategies are essential to guide consumers' choices and produce a substantial population impact on cardiovascular disease risk prevention through nutrition. Our aim was to investigate the prospective association between the Food Standards Agency nutrient profiling system dietary index (FSA-NPS DI) and cardiovascular disease risk. The FSA-NPS has been proposed to serve as a basis for a five-colour nutrition label suggested in France to be put on the front of pack of food products. METHODS AND RESULTS: A total of 6515 participants to the SU.VI.MAX cohort (1994-2007), who completed at least six 24 hour dietary records during the first two years of the study, were followed for a median of 12.4 years (25th-75th percentiles: 11.0-12.6). Multivariable Cox proportional hazards models were used to characterise the associations between FSA-NPS DI (continuous and sex-specific quartiles) and the incidence of cardiovascular diseases. Interactions with individual characteristics were tested; 181 major cardiovascular events were reported (59 myocardial infarctions, 43 strokes, 79 anginas). A higher FSA-NPS DI, characterising poorer food choices, was associated with an overall increase in cardiovascular disease risk (HRfor a 1 point increment = 1.14 (1.03-1.27); HRQ4vs.Q1 = 1.61 (1.05-2.47), Ptrend Q4-Q1 = 0.03). This association tended to be stronger in smokers (HRfor a 1-point increment = 1.39 (1.11-1.73); Pinteraction = 0.01) and those less physically active (HRfor a 1-point increment = 1.26 (1.08-1.46); Pinteraction = 0.04). CONCLUSIONS: Our results suggest that poorer food choices, as reflected by a higher FSA-NPS DI, may be associated with a significant increase in cardiovascular risk, especially in at-risk individuals (smokers and physically inactive persons). This score could be a useful tool for public health prevention strategies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00272428. PMID- 27000100 TI - Why do some women choose to freebirth in the UK? An interpretative phenomenological study. AB - BACKGROUND: Freebirthing or unassisted birth is the active choice made by a woman to birth without a trained professional present, even where there is access to maternity provision. This is a radical childbirth choice, which has potential morbidity and mortality risks for mother and baby. While a number of studies have explored women's freebirth experiences, there has been no research undertaken in the UK. The aim of this study was to explore and identify what influenced women's decision to freebirth in a UK context. METHODS: An interpretive phenomenological approach was adopted. Advertisements were posted on freebirth websites, and ten women participated in the study by completing a narrative (n = 9) and/or taking part in an in-depth interview (n = 10). Data analysis was carried out using interpretative methods informed by Heidegger and Gadamer's hermeneutic phenomenological concepts. RESULTS: Three main themes emerged from the data. Contextualising herstory describes how the participants' backgrounds (personal and/or childbirth related) influenced their decision making. Diverging paths of decision making provides more detailed insights into how and why women's different backgrounds and experiences of childbirth and maternity care influenced their decision to freebirth. Converging path of decision making, outlines the commonalities in women's narratives in terms of how they sought to validate their decision to freebirth, such as through self-directed research, enlisting the support of others and conceptualising risk. CONCLUSION: The UK based midwifery philosophy of woman-centred care that tailors care to individual needs is not always carried out, leaving women to feel disillusioned, unsafe and opting out of any form of professionalised care for their births. Maternity services need to provide support for women who have experienced a previous traumatic birth. Midwives also need to help restore relationships with women, and co-create birth plans that enable women to be active agents in their birthing decisions even if they challenge normative practices. The fact that women choose to freebirth in order to create a calm, quiet birthing space that is free from clinical interruptions and that enhances the physiology of labour, should be a key consideration. PMID- 27000101 TI - A single question about a respondent's perceived financial ability to pay monthly bills explains more variance in health utility scores than absolute income and assets questions. AB - PURPOSE: To evaluate a general question about ability to meet monthly bills as an alternative to direct questions about income and assets in health utility studies. METHODS: We used data from the National Health Measurement Study-a US nationally representative telephone survey collected in 2005-2006. It included health utility measures (EuroQol-5D-3L, Health Utilities Index Mark 3, Short Form 6D, and Quality of Well-being Index) and household income, assets, and financial ability to meet monthly bills questions. Each utility score was regressed on: income and assets (Model 1); difficulty paying bills (DPB) (Model 2); income, assets, and DPB (Model 3). All models used survey weights and adjusted for demographics and education. RESULTS: Among 3666 respondents, as income and assets increased, DPB decreased. The DPB question had fewer missing values (n = 30) than income (n = 311) or assets (n = 373). Model 2 (DPB only) explained more variance in health utility than Model 1 (income and assets only). Including all measures (Model 3) had very modest improvement in R (2), e.g., values were 0.112 (Model 1), 0.166 (Model 2), and 0.175 (Model 3) for EuroQol-5D-3L. CONCLUSIONS: The single question on DPB yields more information and has less missing values than the traditionally used income and assets questions. PMID- 27000103 TI - Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study. AB - BACKGROUND/AIMS: Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. METHODS: In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical. RESULTS: In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff. LESSONS LEARNED: Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well trained study staff; and (4) utilizing technology to automate procedures whenever possible. CONCLUSION: This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies. PMID- 27000102 TI - Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China. AB - BACKGROUND: Dyslipidemia in pregnancy are associated with gestational diabetes mellitus (GDM), preeclampsia, preterm birth and other adverse outcomes, which has been extensively studied in western countries. However, similar studies have rarely been conducted in Asian countries. Our study was aimed at investigating the associations between maternal dyslipidemia and adverse pregnancy outcomes among Chinese population. METHODS: Data were derived from 934 pairs of non diabetic mothers and neonates between 2010 and 2011. Serum blood samples were assayed for fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) concentrations during the first, second and third trimesters. The present study explored the associations between maternal lipid profile and pregnancy complications and perinatal outcomes. The pregnancy complications included GDM, preeclampsia and intrahepatic cholestasis of pregnancy (ICP); the perinatal outcomes included preterm birth, small/large for gestational age (SGA/LGA) infants and macrosomia. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated and adjusted via stepwise logistic regression analysis. Optimal cut-off points were determined by ROC curve analysis. RESULTS: After adjustments for confounders, every unit elevation in third-trimester TG concentration was associated with increased risk for GDM (OR = 1.37, 95% CI: 1.18-1.58), preeclampsia (OR = 1.50, 95% CI: 1.16-1.93), ICP (OR = 1.28, 95% CI: 1.09-1.51), LGA (OR = 1.13, 95% CI: 1.02-1.26), macrosomia (OR = 1.19, 95% CI: 1.02-1.39) and decreased risk for SGA (OR = 0.63, 95% CI: 0.40-0.99); every unit increase in HDL C concentration was associated with decreased risk for GDM and macrosomia, especially during the second trimester (GDM: OR = 0.10, 95% CI: 0.03-0.31; macrosomia: OR = 0.25, 95% CI: 0.09-0.73). The optimal cut-off points for third trimester TG predicting GDM, preeclampsia, ICP, LGA and SGA were separately >= 3.871, 3.528, 3.177, 3.534 and <= 2.530 mmol/L. The optimal cut-off points for third-trimester HDL-C identifying GDM, macrosomia and SGA were respectively <= 1.712, 1.817 and >= 2.238 mmol/L. CONCLUSIONS: Among Chinese population, maternal high TG in late pregnancy was independently associated with increased risk of GDM, preeclampsia, ICP, LGA, macrosomia and decreased risk of SGA. Relative low maternal HDL-C during pregnancy was significantly associated with increased risk of GDM and macrosomia; whereas relative high HDL-C was a protective factor for both of them. PMID- 27000104 TI - Towards universal access to skilled birth attendance: the process of transforming the role of traditional birth attendants in Rural China. AB - BACKGROUND: Institution-based childbirth, with the ultimate goal of universal access to skilled birth attendance (SBA), has been selected as a key strategy to reduce the maternal mortality rate in many developing countries. However, the question of how to engage traditional birth attendants (TBAs) in the advocacy campaign for SBA poses a number of challenges. This paper aims to demonstrate how TBAs in rural regions of China have been integrated into the health system under a policy of institutional delivery. METHODS: Research was conducted through literature and document reviews and individual in-depth interviews with stakeholders of the safe motherhood program in rural Guangxi Zhuang Autonomous Region, China. A total of 33 individual interviews were conducted with regional and local politicians, policy makers, health managers, health providers, civil society members, village cadres for women affairs, former TBAs, village maternal health workers, mothers and their mother-in-laws. RESULTS: Since 1998, TBA's traditional role of providing in-home care during childbirth has been restructured and their social role has been strengthened in rural Guangxi. TBAs were redesigned to function as the linkage between women and the health system. A new policy in 1999 shifted the role of TBAs to village maternal health workers whose responsibilities were mainly to promote perinatal care and institution based delivery of pregnant women. This successful transformation involved engaging with government and other actors, training TBAs for their new role, and providing incentives and sanctions for human resources management. CONCLUSIONS: The China experience of transforming the role of TBAs in Guangxi rural area is an example of successfully engaging TBAs in promoting institution-based childbirth. PMID- 27000105 TI - Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients. AB - Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n = 28) or intervention (n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n = 28) showed increased time in euglycaemia (mean +/- standard deviation) by 1.4 +/- 3.5 h/day (p = 0.0427) associated with reduction in HbA1c from 77 +/- 15 to 67 +/- 13 mmol/mol (p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n = 25) showed reduction in hypoglycaemia from 1.4 +/- 1.7 to 0.8 +/- 0.8 h/day (p = 0.0472) associated with a marginal HbA1c decrease from 75 +/- 10 to 72 +/- 8 mmol/mol (p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients. PMID- 27000106 TI - Functional deficiency of vitamin K in hemodialysis patients in Upper Silesia in Poland. AB - PURPOSE: Functional vitamin K deficiency (both K1 and K2) is postulated to be one of the most relevant links between chronic kidney disease and vascular calcification in hemodialysis (HD) patients. Recommended dietary restrictions in HD patients superimposed on diversity of eating habits across the countries may affect the prevalence of functional vitamin K deficiency. The aim of this study was to determine the level of functional vitamin K deficiency and its relation to vitamin K1 intake in HD patients in Upper Silesia in Poland. METHODS: Protein induced vitamin K absence or antagonist-II (PIVKA-II) and undercarboxylated matrix Gla protein (ucMGP) were assessed by ELISA in 153 stable, prevalent HD patients and 20 apparently healthy adults (to establish normal ranges for PIVKA II and ucMGP). Daily phylloquinone intake was assessed using a food frequency questionnaire. RESULTS: PIVKA-II and ucMGP levels were increased in 27.5 and 77.1 % of HD patients in comparison with the reference ranges in apparently healthy controls, respectively. In 45 % of cases, the increased PIVKA-II level was explained by insufficient phylloquinone intake for Polish population (recommended intake: >55 MUg for women and >65 ug for men). Applying ROC analysis, we showed that vitamin K1 intake below 40.2 ug/day was associated with increased PIVKA-II levels. There was no correlation between vitamin K1 intake and plasma concentration of ucMGP, or between PIVKA-II and ucMGP. CONCLUSIONS: (1) Functional vitamin K1 deficiency is explained by low vitamin K1 intake in less than half of HD patients. (2) Undercarboxylated matrix Gla protein level is a poor surrogate for functional vitamin K1 deficiency. PMID- 27000108 TI - Neurophysiologic Correlates of Headache Pain in Subjects With Major Depressive Disorder. AB - BACKGROUND: Headache pain is often comorbid with major depressive disorder (MDD) and is associated with greater symptom burden, disability, and suicidality. The biological correlates of headache pain in MDD, however, remain obscure. The purpose of this study was to examine the association between brain oscillatory activity and headache pain in MDD subjects. METHODS: A total of 64 subjects with MDD who were free of psychoactive medications were evaluated for severity of headache pain in the past week. Brain function was assessed using resting-state quantitative electroencephalography (qEEG). We derived cordance in the theta (4-8 Hz) and alpha (8-12 Hz) frequency bands at each electrode, and examined correlations with headache pain in regions of interest while controlling for depression severity. Frontal and posterior asymmetry in alpha power was calculated in regions of interest. RESULTS: Headache pain severity was associated with depression severity ( r = 0.447, P < .001). In bilateral frontal and right posterior regions, alpha cordance was significantly associated with headache intensity, including when controlling for depression severity. The direction of the correlation was positive anteriorly and negative posteriorly. Frontal left dominant alpha asymmetry correlated with severity of headache but not depression symptoms. CONCLUSION: Alterations in brain oscillations identified by alpha cordance and alpha asymmetry may be associated with the pathophysiology of headache pain in depression. These findings should be prospectively confirmed. PMID- 27000107 TI - Severe myositis of the hip flexors after pre-operative chemoradiation therapy for locally advanced rectal cancer: case report. AB - BACKGROUND: The use of neoadjuvant radiation therapy and chemotherapy in the treatment of locally advanced rectal adenocarcinoma has been shown to reduce disease recurrence when combined with surgery and adjuvant chemotherapy. We report a case of a patient who developed a debilitating bilateral myopathy of the hip flexors after successful treatment for rectal cancer. To the best of our knowledge, this is the first such complication from radiation therapy reported in a patient with colorectal cancer. The disproportionate severity of our patient's myopathy relative to the dose of radiation used also makes this case unique among reports of neuromuscular complications from radiation therapy. CASE PRESENTATION: The patient is a 65-year-old male with node negative, high-grade adenocarcinoma of the rectum penetrating through the distal rectal wall. He underwent neoadjuvant concurrent pelvic radiation therapy and capecitabine-based chemotherapy, followed by abdominoperineal resection and post-operative FOLFOX chemotherapy. Five months post-completion of pelvic radiotherapy and 2 months after the completion of adjuvant chemotherapy, he presented with bilateral weakness of the iliopsoas muscles and severe pain radiating to the groin. The patient improved with 40 mg/d of prednisone, which was gradually tapered to 2 mg/d over 6 months, with substantial recovery of muscle strength and elimination of pain. CONCLUSIONS: The timing, presentation and response of our patient's symptoms to corticosteroids are most consistent with a radiation recall reaction. Radiation recall is a phenomenon whereby previously irradiated tissue becomes vulnerable to toxicity by subsequent systemic therapy and is rarely associated with myopathies. Radiation recall should be considered a potential complication of neoadjuvant radiation therapy for rectal cancer, and for ongoing research into the optimization of treatment for these patients. Severe myopathies caused by radiation recall may be fully reversible with corticosteroid treatment. PMID- 27000109 TI - Induced Higher-order aberrations after Laser In Situ Keratomileusis (LASIK) Performed with Wavefront-Guided IntraLase Femtosecond Laser in moderate to high Astigmatism. AB - BACKGROUND: Wavefront-guided Laser-assisted in situ keratomileusis (LASIK) is a widespread and effective surgical treatment for myopia and astigmatic correction but whether it induces higher-order aberrations remains controversial. The study was designed to evaluate the changes in higher-order aberrations after wavefront guided ablation with IntraLase femtosecond laser in moderate to high astigmatism. METHODS: Twenty-three eyes of 15 patients with moderate to high astigmatism (mean cylinder, -3.22 +/- 0.59 dioptres) aged between 19 and 35 years (mean age, 25.6 +/- 4.9 years) were included in this prospective study. Subjects with cylinder >= 1.5 and <=2.75 D were classified as moderate astigmatism while high astigmatism was >=3.00 D. All patients underwent a femtosecond laser-enabled (150-kHz IntraLase iFS; Abbott Medical Optics Inc) wavefront-guided ablation. Uncorrected (UDVA), corrected (CDVA) distance visual acuity in logMAR, keratometry, central corneal thickness (CCT) and higher-order aberrations (HOAs) over a 6 mm pupil, were assessed before and 6 months, postoperatively. The relationship between postoperative change in HOA and preoperative mean spherical equivalent refraction, mean astigmatism, and postoperative CCT were tested. RESULTS: At the last follow-up, the mean UDVA was increased (P < 0.0001) but CDVA remained unchanged (P = 0.48) and no eyes lost >=2 lines of CDVA. Mean spherical equivalent refraction was reduced (P < 0.0001) and was within +/-0.50 D range in 61% of eyes. The average corneal curvature was flatter by 4 D and CCT was reduced by 83 MUm (P < 0.0001, for all), postoperatively. Coma aberrations remained unchanged (P = 0.07) while the change in trefoil (P = 0.047) postoperatively, was not clinically significant. The 4th order HOAs (spherical aberration and secondary astigmatism) and the HOA root mean square (RMS) increased from -0.18 +/ 0.07 MUm, 0.04 +/- 0.03 MUm and 0.47 +/- 0.11 MUm, preoperatively, to 0.33 +/- 0.19 MUm (P = 0.004), 0.21 +/- 0.09 MUm (P < 0.0001) and 0.77 +/- 0.27 MUm (P < 0.0001), six months postoperatively. The change in spherical aberration after the procedure increased with an increase in the degree of preoperative myopia. CONCLUSIONS: Wavefront-guided IntraLASIK offers a safe and effective option for vision and visual function improvement in astigmatism. Although, reduction of HOA is possible in a few eyes, spherical-like aberrations are increased in majority of the treated eyes. PMID- 27000111 TI - Echocardiographic pattern of rheumatic valvular disease in a contemporary sub Saharan African pediatric population: an audit of a major cardiac ultrasound unit in Yaounde, Cameroon. AB - BACKGROUND: Rheumatic Heart Disease (RHD) remains a major cause of childhood acquired heart disease in developing countries. However reported echocardiographic features are limited to a few countries. This report is on the demographic and echocardiographic features of RHD in children using data from the largest referral hospital in Yaounde, the capital city of Cameroon. METHODS: The register of the cardiac ultrasound unit of the Yaounde General Hospital for the period 2003-2013 served as basis for data collection. RHD diagnosis was based on the World Heart Federation Criteria for the diagnosis of RHD. Demographic data, pattern of valve lesions and severity were analyzed. RESULTS: A total of 1130 first echocardiographic examinations were performed in children aged <= 18 years. Sixty-five (5.8 %) had a definite echocardiographic diagnosis of RHD with their mean age being 11.8 years (SD 3.6) and 31 (47.1 %) being boys. The commonest primary reasons for requesting an echocardiographic examination were a clinical diagnosis of RHD (24.6 %) without heart failure, a clinical diagnosis of heart failure (24.6 %), and heart murmurs (21.5 %). Isolated mitral regurgitation was the most common valve lesion (49.2 %) and was frequently associated with aortic regurgitation (35.4 %). Severe lesions were found in 63.3 % of participants. No right heart lesion was reported. CONCLUSIONS: A sizable proportion of children undergoing echocardiographic examination at this major referral hospital in Cameroon had RHD, with lesions found only on the left heart. These lesions predominated on the mitral valve, were commonly associated with aortic regurgitation, and more often severe. PMID- 27000110 TI - Cannabinoid-glutamate interactions in the regulation of food intake in neonatal layer- type chicks: role of glutamate NMDA and AMPA receptors. AB - The involvement of the endocannabinoid system in the brain functions is likely the conclusion of its capability to interact with specific neurotransmitters in several brain regions. The present study was designed to examine the role of the glutamatergic system on cannabinoid-induced hyperphagia in chicken. In this survey 10 experiments designed to investigate interaction of cannabinoidergic and glutamatergic systems on feeding behavior in neonatal chickens. In experiment 1, chicken were intracerebroventricular (ICV) injected with saline, 2-AG (2 Arachidonoylglycerol, 5.28 nmol, CB1 receptors agonist), MK-801(NMDA receptor antagonist, 15 nmol) and co-administration of 2-AG + MK-801. In experiment 2, injection of saline, 2-AG (5.28 nmol), CNQX) AMPA/kainate receptor antagonist, 390 nmol) and their combination (2-AG + CNQX) was done. In Experiment 3, injections were saline, 2-AG (5.28 nmol), AIDA)mGluR1 antagonist, 2 nmol) and 2 AG + AIDA. Experiments 4 and 5 were similar to experiment 3, except birds injected with LY341495 (mGLUR2 glutamate antagonist, 150 nmol) and UBP1112 (mGLUR3 glutamate antagonist, 2 nmol) instead of AIDA. Experiments 6-10 followed the procedure similar to experiments 1-5, except chickens received ICV injection of CB65 (CB2 receptor agonist, 3 nmol), instead of 2-AG. Then the cumulative food intake measured until 120 min post injection. According to the results, ICV injection of 2-AG and CB65 significantly increased food intake (P < 0.001). Co injection of 2-AG and MK-801 significantly amplified hyperphagic effect of CB1 receptors agonist(P < 0.001). Moreover, co-administration of CB65 plus CNQX significantly increased CB65- induced hyperphagia in FD3 neonatal layer-type chickens (P < 0.001). These results suggest there is an interaction between endocannabinoids and glutamatergic systems via NMDA and AMPA receptors in feeding behavior of neonatal layer-type chickens. PMID- 27000112 TI - Characterization of a novel H3N2 influenza virus isolated from domestic ducks in China. AB - Cases of human infection with a novel H7N9 avian influenza virus (AIV) were first reported in March 2013, which caused 115 deaths within a single year. Beyond that, other subtypes of H7 AIV were isolated from poultry in eastern China during the same period, including H7N7 and H7N2 AIV. In the present study, a subtype H3N2 AIV was isolated from ducks from Anhui Province, China. Sequence and phylogenetic analyses revealed that seven gene segments of this virus showed the highest sequence homology with that of the H7 subtype influenza virus, which is presumed to be the reassortants of the H3 and H7 subtypes AIV. The present study also reconfirmed that the reassortment between the H7 subtype and waterfowl originating AIVs universally occurred in waterfowl. Animal inoculation tests showed that the virus has low pathogenicity in chickens; however, it could be replicated in the lungs of mice. The emergence of this H3N2 isolate emphasizes the importance of enhancing the surveillance of waterfowl-originating AIVs, the identification of novel reassortant strains, and characterization of their biological properties. PMID- 27000114 TI - Erratum to: Elemental analysis of soils and Salix polaris in the town of Pyramiden and its surroundings (Svalbard). PMID- 27000113 TI - Clinical correlates of vitamin D deficiency in established psychosis. AB - BACKGROUND: Suboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis. METHODS: Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and "sufficient" Vitamin D as above 30 ng/ml (>50 nmol/L). RESULTS: The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14 % (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = -0.220, p < 0.002), triglycerides (r = -0.160, p = 0.024), total cholesterol (r = -0.144, p = 0.043), fasting glucose (r = -0.191, p = 0.007), HbA1c (r = -0.183, p = 0.01), and serum CRP levels (r = -0.211, p = 0.003) and were linked to the presence of metabolic syndrome. CONCLUSIONS: This is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk. TRIAL REGISTRATION: ISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010. PMID- 27000115 TI - Chemical characteristics of rainwater in Sichuan basin, a case study of Ya'an. AB - Rainwater chemistry was investigated at a semi-rural site in Ya'an, Sichuan basin with rain samples collected from May 2013 to July 2014. The rainwater pH values ranged from 3.25 to 6.86, with an annual volume-weighted mean (VWM) of 4.38, and the acid rain frequency was 74 %. Such severe acidification, 15 % of the total events showed a pH below 4.0, attributed to the deficiency of Ca(2+), significant anthropogenic pollution contribution, and rainy pattern to this area. The annual VWM of total ions concentration was 477.19 MUeq/L. NH4 (+) was the most abundant ionic species, followed by SO4 (2-), NO3 (-), Ca(2+), Cl(-), Na(+), K(+), Mg(2+), and F(-) in a descending order. The total ionic concentrations presented a seasonal trend of lower values in autumn and summer but higher ones in winter and spring. Based on enrichment factor, correlation analysis and principle component analysis, three factors were identified: factor 1 (NH4 (+), SO4 (2-), NO3 (-), K(+), and Cl(-), 47.45 % of the total variance) related to anthropogenic sources (coal/fuel combustion, biomass burning and agriculture), factor 2 (Ca(2+), Mg(2+), Na(+), and Cl(-), 34.01 % of the total variance) associated with natural sources, and factor 3 (H(+), 11.78 % of the total variance) related to free acidity. Back trajectory analysis indicates that the rainwater chemistry in Ya'an was mainly affected by regional air masses from Sichuan basin. Long-range transported air masses from southwest with heavy anthropogenic pollution increased the total ion concentration and acidity of rainwater. Considering its special topography, anthropogenic emissions from regional and long-range transport (especially from southwest) must be controlled effectively to improve the acid rain condition of non-urban areas in Sichuan basin. PMID- 27000116 TI - Heavy metals in road dust from Xiandao District, Changsha City, China: characteristics, health risk assessment, and integrated source identification. AB - The physicochemical properties and the contents of metals (Cu, Zn, Pb, Cd, Cr, and Fe) in 51 road dust samples from Xiandao District (XDD) were investigated. Enrichment factor (EF), multivariate statistics, geostatistics, and health risk assessment model were adopted to study the spatial pollution pattern and to identify the priority pollutants and regions of concern and sources of studied metals. The mean EFs revealed the following order: Cd > Zn ~ Pb ~ Cu > Cr. For non-carcinogenic effects, the exposure pathway which resulted in the highest levels of exposure risk for children and adults was ingestion, followed by dermal contact and inhalation. Hazard index (HI) values for the studied metals at each site were within the safe level of 1 except maximum HI Cr (1.08) for children. The carcinogenic risk (CR) for Cd and Cr at each site was within the acceptable risk level (1E-06) except CR Cr (1.08E-06) for children in the road intersection between the Changchang highway and the Yuelin highway. Cr was identified as the priority pollutant followed by Pb and Cd with consideration of the local population distribution. Spatially, northwest and northeast of XDD were regarded as the priority regions of concern. Results based on the proposed integrated source identification method indicated that Pb was probably sourced from traffic related sources, Cd was associated with the dust organic material mainly originated from industrial sources, and Cr was mainly derived from both sources. PMID- 27000117 TI - Effects of returning NF concentrate on the MBR-NF process treating antibiotic production wastewater. AB - The optimization of the nanofiltration (NF) concentrate backflow ratio (R cb) and the influence of the NF concentrate on the performance of membrane bioreactor nanofiltration (MBR-NF) process treating antibiotic production wastewater were investigated on a laboratory scale. The R cb was optimized at 60 % based on the removal rates of chemical oxygen demand (COD) and NH4 (+)-N by MBR. Data analyses indicated that salinity brought by NF concentrate is the major driver leading to the decrease of sludge activity, especially at a high R cb. EPS analysis showed that electric conductivity (EC), proteins in soluble microbial products (SMP), and SMP brought by NF concentrate are the dominant factors causing the severe membrane fouling in MBR. Furthermore, undegradable substances including fulvic acid-like and humic acid-like compounds accumulated in NF concentrate showed significant influence on fouling of NF. MBR could well degrade small MW compounds in NF concentrate, which confirmed the enhancement of organic removal efficiency by recycling the NF concentrate to MBR. The MBR-NF process showed a relatively stable performance at the R cb of 60 % (volume reduction factor (VRF) = 5), and the NF permeate could satisfy the water quality standard for fermentation process with a water recovery rate of 90.9 %. PMID- 27000118 TI - Human contribution to trace elements in urban areas as measured in holm oak (Quercus ilex L.) bark. AB - The effect of human activities on the presence of trace elements in the atmosphere was evaluated by analyzing samples of holm oak bark, collected in Italy in a large city, in a small town, and in a reference area, scarcely inhabited. In all cases, point sources of pollution were excluded (e.g., industries and incinerators). The concentrations of As, Cd, Co, Cu, Fe, Mn, Ni, Pb, V, and Zn were measured using inductively coupled plasma optical emission spectrometry (ICP-OES). The element concentrations in the small town are not different from the reference area, except for Pb and Cu, while the samples collected in the large city show higher concentrations of Co, Cu, Fe, Ni, Pb, V, and Zn with respect to the rural area. In particular, the Pb levels in the large city are approximately 16 times higher than in the reference site, and five times higher than in the small town. Most element concentrations are correlated in the large city, while in the reference site, only a few significant correlations between elements were found. Even in the absence of specific sources of pollution, populations living in big cities are exposed to higher concentrations of trace elements than those living in rural environments or in small urban centers. PMID- 27000119 TI - Contamination and human health risk of lead in soils around lead/zinc smelting areas in China. AB - Pb/Zn smelting, an important economic activity in China, has led to heavy environmental pollution. This research reviewed studies on soil Pb contamination at Pb/Zn smelting sites in China published during the period of 2000 to 2015 to clarify the total levels, spatial changes, and health risks for Pb contamination in soils at local and national scales. The results show that Pb contents in surface soils at 58 Pb/Zn smelting sites in China ranged from 7 to 312,452 mg kg( 1) with an arithmetic average, geometric average, and median of 1982, 404, and 428 mg kg(-1), respectively (n = 1011). Surface soil Pb content at these smelting sites decreased from an average of 2466 to 659 mg kg(-1), then to 463 mg kg(-1) as the distance from the smelters increased from <1000 to 1000~2000 m, and then to >2000 m. With respect to variation with depth, the average soil Pb content at these sites gradually decreased from 986 mg kg(-1) at 0- to 20-cm depth to 144 mg kg(-1) at 80- to 100-cm depth. Approximately 78 % of the soil samples (n = 1011) at the 58 Pb/Zn smelting sites were classified as having high Pb pollution levels. Approximately 34.2 and 7.7 % of the soil samples (n = 1011) at the 58 Pb/Zn smelting sites might pose adverse health effects and high chronic risks to children, respectively. The Pb/Zn smelting sites in the southwest and southeast provinces of China, as well as Liaoning province, were most contaminated and thus should receive priority for remediation. PMID- 27000120 TI - Occipital event-related potentials to addiction-related stimuli in detoxified patients with alcohol dependence, and their association with three-month relapse. AB - BACKGROUND: Understanding the biological underpinnings of relapse in alcohol dependency is a major issue in addiction research. Based on recent evidence regarding the relevance of occipital visual evoked response potentials (ERPs) in addiction research, and its significance for relapse research, we assessed occipital ERPs to alcohol- and non-alcohol-related stimuli in recently detoxified patients and controls. METHODS: Thirty recently detoxified patients with alcohol addiction, and 31 healthy control subjects, were assessed in a Go and a NoGo condition, each using three visual stimuli: tea, juice and beer. In the "Go" condition, subjects had to respond to the juice (12.5 %) and the beer stimulus (12.5 %), and ignore the tea picture (75 %). In the "NoGo" condition, subjects had to respond to the tea picture (75 %) and ignore the juice and the beer picture (12.5 % each). The subjects' EEGs were analyzed with regard to the occipital P100 and N170 ERP components. Patients were then evaluated for relapse 3 months after this initial assessment. RESULTS: P100 amplitudes differed between conditions and between stimuli, and we found a condition x electrode interaction. However, none of these P100 results involved group or relapse-status effects. N170 amplitudes in patients were elevated as compared to controls. Additionally, patients' heightened N170 amplitudes in response to the alcohol-related (beer) stimulus were found only under the NoGo condition, where subjects had to react to the frequent tea stimulus and ignore the beer and the juice stimuli, thus resulting in a condition x stimulus x group interaction. Patients reporting relapse in a 3-month follow-up assessment showed larger NoGo N170 alcohol cue related ERP amplitudes and increased depression scores as compared to patients who stayed abstinent. Depression was related to shortened P100 latencies in patients, but unrelated to the N170 NoGo cue-reactivity effect. CONCLUSIONS: Our results indicate a sensitivity of occipital ERPs to addiction-related stimuli when these act as non-targets. Recently detoxified patients may be vulnerable to addiction-related cues when these occur outside the focus of directed attention, thereby circumventing intentional control processes. Furthermore, ERPs to addiction-related stimuli may be useful as a predictor of abstinence success in recently detoxified patients. PMID- 27000121 TI - Euphorins A-H: bioactive diterpenoids from Euphorbia fischeriana. AB - Phytochemical investigation of the roots of Euphorbia fischeriana resulted in the isolation of 23 diterpenoids (1-23), which were classified into five subtypes, namely, ent-rosane (1-9), ent-abietane (10-16), ent-kaurane (17), ingenane (18 22), and lathyrane (23). The chemical structures of eight new compounds, namely, euphorin A (4), B (5), C (7), D (9), E (13), F (14), G (15), and H (16), were elucidated on the basis of extensive 1D and 2D NMR spectroscopic analyses, as well as single crystal X-ray structure analysis. A number of compounds (2, 6, 7, 10, 11, 13, 16, 19, 20, 22, and 23) showed inhibitory activity on the formation of mammospheres in human breast cancer MCF-7 cells at a final concentration of 10 MUM, suggesting the potential of these bioactive diterpenoids for further investigation of the action targeting cancer stem cells. PMID- 27000122 TI - Non-fatal suicidal behaviour in rural Ethiopia: a cross-sectional facility- and population-based study. AB - BACKGROUND: Injury related to self-harm is one of the leading causes of global disease burden. As a formative work for a programme to implement comprehensive mental healthcare in a rural district in Ethiopia, we determined the 12-month prevalence of non-fatal suicidal behaviour as well as factors associated with this behaviour to understand the potential burden of the behaviour in the district. METHOD: Population-based (n = 1485) and facility-based (n = 1014) cross sectional surveys of adults, using standardised, interview-based measures for suicidality (items on suicide from the Composite International Diagnostic Interview), depressive symptoms (the Patient Health Questionnaire) and alcohol use disorders (Alcohol Use Disorder Investigation Test; AUDIT). RESULTS: The overall 12-month prevalence of non-fatal suicidal behaviour, consisting of suicidal ideation, plan and attempt, was 7.9 % (95 % Confidence Interval (CI) = 6.8 % to 8.9 %). The prevalence was significantly higher in the facility sample (10.3 %) compared with the community sample (6.3 %). The 12-month prevalence of suicide attempt was 4.4 % (95 % CI = 3.6 % to 5.3 %), non-significantly higher among the facility sample (5.4 %) compared with the community sample (3.8 %). Over half of those with suicidal ideation (56.4 %) transitioned from suicidal ideation to suicide attempt. Younger age, harmful use of alcohol and higher depression scores were associated significantly with increased non-fatal suicidal behaviours. The only factor associated with transition from suicidal ideation to suicide attempt was high depression score. Only 10.5 % of the sample with suicidal ideation had received any treatment for their suicidal behaviour: 10.8 % of the community sample and 10.2 % of the facility sample. Although help seeking increased with progression from ideation to attempt, there was no statistically significant difference between the groups. CONCLUSION: Non-fatal suicidal behaviour is an important public health problem in this rural district. A more in depth understanding of the context of the occurrence of the behaviour, improving access to care and targeting depression and alcohol use disorder are important next steps. The role of other psychosocial factors should also be explored to assist the provision of holistic care. PMID- 27000123 TI - Drug Abuse, HIV, and HCV in Asian Countries. AB - Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections. PMID- 27000124 TI - What Factors Contribute to Intimate Partner Violence Against Women in Urban, Conflict-Affected Settings? Qualitative Findings from Abidjan, Cote d'Ivoire. AB - Rapid urbanization is a key driver of the unique set of health risks facing urban populations. One of the most critical health hazards facing urban women is intimate partner violence (IPV). In post-conflict urban areas, women may face an even greater risk of IPV. Yet, few studies have examined the IPV experiences of urban-dwelling, conflict-affected women, including those who have been internally displaced. This study qualitatively examined the social and structural characteristics of the urban environment that contributed to the IPV experiences of women residing in post-conflict Abidjan, Cote d'Ivoire. Ten focus groups were conducted with men and women, both internally displaced (IDPs) and non-displaced. Lack of support networks, changing gender roles, and tensions between traditional gender norms and those of the "modern" city were reported as key contributors to IPV. Urban poverty and with it unemployment, food insecurity, and housing instability also played a role. Finally, IDPs faced heightened vulnerability to IPV as a result of displacement and discrimination. The relationship between economic strains and IPV are similar to other conflict-affected settings, but Abidjan's urban environment presented other unique characteristics contributing to IPV. Understanding these factors is crucial to designing appropriate services for women and for implementing IPV reduction interventions in urban areas. Strengthening formal and informal mechanisms for help-seeking, utilizing multi modal interventions that address economic stress and challenge inequitable gender norms, as well as tailoring programs specifically for IDPs, are some considerations for IPV program planning focused on conflict-affected women in urban areas. PMID- 27000126 TI - Para-Aortic Dissection in Pancreaticoduodenectomy with Mesopancreas Excision for Pancreatic Head Carcinoma: Not Only an N-Staging Matter. PMID- 27000125 TI - Neighborhood Socioeconomic Status in Relation to Serum Biomarkers in the Black Women's Health Study. AB - Lower neighborhood socioeconomic status (SES) is associated with higher cardiovascular disease (CVD) risk. Black women have a higher CVD risk and are more likely to live in poor neighborhoods than white women. We examined the association of neighborhood SES with several CVD biomarkers using data from the Black Women's Health Study (BWHS), a follow-up study of US black women reporting high levels of education and income. Blood specimens of 418 BWHS participants were assayed for C-reactive protein (CRP), hemoglobin A1C (hgA1C), and high density lipoprotein (HDL) cholesterol. US Census block group data were linked to the women's addresses to reflect neighborhood SES. Multivariable-adjusted mixed linear regression models that adjusted for person-level SES and for cardiovascular risk factors were used to assess CRP, hgA1C, and HDL levels in relation to quintiles of neighborhood SES. Women living in the poorest neighborhoods had the least favorable biomarker levels. As neighborhood SES increased, CRP decreased (P for trend = 0.01), hgA1C decreased (P for trend = 0.07), and HDL increased (P for trend = 0.19). These associations were present within strata of individual educational level. The present findings suggest that neighborhood environments may affect physiological processes within residents independently of individual SES. PMID- 27000127 TI - Scoring System for the Management of Acute Gallstone Pancreatitis: Cost Analysis of a Prospective Study. AB - Predicting the presence of a persistent common bile duct (CBD) stone is a difficult and expensive task. The aim of this study is to determine if a previously described protocol-based scoring system is a cost-effective strategy. The protocol includes all patients with gallstone pancreatitis and stratifies them based on laboratory values and imaging to high, medium, and low likelihood of persistent stones. The patient's stratification then dictates the next course of management. A decision analytic model was developed to compare the costs for patients who followed the protocol versus those that did not. Clinical data model inputs were obtained from a prospective study conducted at The Mount Sinai Medical Center to validate the protocol from Oct 2009 to May 2013. The study included all patients presenting with gallstone pancreatitis regardless of disease severity. Seventy-three patients followed the proposed protocol and 32 did not. The protocol group cost an average of $14,962/patient and the non protocol group cost $17,138/patient for procedural costs. Mean length of stay for protocol and non-protocol patients was 5.6 and 7.7 days, respectively. The proposed protocol is a cost-effective way to determine the course for patients with gallstone pancreatitis, reducing total procedural costs over 12 %. PMID- 27000128 TI - Obturator Canal Lymph Node Metastasis from Rectal Carcinoid Tumors: Total Mesorectal Excision May Be Insufficient. AB - BACKGROUND: Optimal surgical treatment for small early rectal carcinoids is controversial. Large tumors (greater than 2 cm) and those with imaging evidence of lymph node metastasis are generally treated by low anterior resection (LAR) with total mesorectal excision (TME). We first observed and reported that midgut carcinoid with extensive mesenteric lymphadenopathy often develops alternated lymphatic drainage pathways. We hypothesize that rectal carcinoids have the same potential to develop alternated lymphatic pathways outside the mesorectal envelope, which allows tumor deposits to be missed by traditional TME. METHODS: Twenty-two consecutive rectal carcinoid surgical patient charts were reviewed to determine if alternated lymphatic drainage occurred and resulted in extra mesorectal metastasis. We attempted to identify any risk factor(s) that may lead to developing such alternated lymphatic drainage pathways. RESULTS: Thirteen patients underwent initial LAR with TME (13/22, 59 %) and nine underwent a staged debulking for locoregional residual disease or regional/distant metastasis after previous resection (9/22, 41 %). Fourteen (14/22, 64 %) underwent radio-guided surgery in attempt to achieve a higher level of pelvic/distant metastatic disease detection and debulking. Six patients (6/22, 27 %) had obturator canal lymph node metastases confirmed histologically. CONCLUSIONS: Based on our study, at least 27 % of rectal carcinoid patients may have extra-mesorectal metastasis that would be missed by the traditional TME. Radio-guided surgery can identify and remove such metastasis. The effect of having such extra-mesorectal metastasis and its surgical removal on long-term survival has yet to be determined. PMID- 27000129 TI - Successful Breastfeeding Outcome of a Woman with a Nevus of the Nipple: A Case Study. AB - Unusual conditions of the nipple and breast may interfere with breastfeeding. Nevi of the nipple are rare, and breastfeeding outcomes of women with this condition have only been briefly reported in the literature. This case describes the proactive lactation management and successful breastfeeding outcome of a woman with a large, roughly textured nevus located on her right nipple and areola. PMID- 27000130 TI - Physician Preferences for Physician-Targeted HIV Testing Campaigns. AB - The U.S. Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force issued HIV testing recommendations, encouraging physicians to routinely test all adult patients for HIV. Studies have found that not all physicians are abiding by these guidelines, but that physician recommendations for HIV testing could encourage patients to get tested. Our study sought to determine physician preferences for a physician-targeted campaign to encourage them to offer HIV tests to their patients. The study took place across 19 publicly-funded community health centers. A web-based survey was sent to primary care physicians, assessing their preferences for physician-targeted HIV testing campaign elements. Response frequencies were calculated for each element. 175 physicians participated. Campaign elements were divided into "HIV Testing Information," "Communication Tools," and "Promotion Strategies." Physicians selected receiving a copy of the latest HIV testing recommendations, having patients ask for the HIV test, and receiving an EMR alert for HIV testing as their top elements for each category, respectively. An effective physician HIV testing campaign should include information about HIV testing recommendations, proof of patient receptiveness to HIV testing, and strategies to prompt HIV testing conversations. A multi-faceted approach combining patient and physician prompts to discuss HIV testing might be the most effective method to improve HIV testing rates. PMID- 27000131 TI - Extending Our Understanding of Burnout and Its Associated Factors: Providers and Staff in Primary Care Clinics. AB - Burnout has been identified as an occupational hazard in the helping professions for many years and is often overlooked, as health-care systems strive to improve cost and quality. The Maslach Burnout Inventory (MBI) and the Areas of Worklife Survey (AWS) are tools for assessing burnout prevalence and its associated factors. We describe how we used them in outpatient clinics to assess burnout for multiple job types. Traditional statistical techniques and seemingly unrelated regression were used to describe the sample and evaluate the association between work life domains and burnout. Of 838 eligible participants, 467 (55.7%) were included for analysis. Burnout prevalence varied across three job categories: providers (37.5%), clinical assistants (24.6%), and other staff (28.0%). It was not related to age, gender, or years of tenure but was lower in part-time workers (24.6%) than in full-time workers (33.9%). Analysis of the AWS subscales identified organizational correlates of burnout. Accurately identifying and defining the operative system factors associated with burnout will make it possible to create successful interventions. Using the MBI and the AWS together can highlight the relationship between system work experiences and burnout. PMID- 27000132 TI - Application of a Dual-Arm Robot in Complex Sample Preparation and Measurement Processes. AB - Automation systems with applied robotics have already been established in industrial applications for many years. In the field of life sciences, a comparable high level of automation can be found in the areas of bioscreening and high-throughput screening. Strong deficits still exist in the development of flexible and universal fully automated systems in the field of analytical measurement. Reasons are the heterogeneous processes with complex structures, which include sample preparation and transport, analytical measurements using complex sensor systems, and suitable data analysis and evaluation. Furthermore, the use of nonstandard sample vessels with various shapes and volumes results in an increased complexity. The direct use of existing automation solutions from bioscreening applications is not possible. A flexible automation system for sample preparation, analysis, and data evaluation is presented in this article. It is applied for the determination of cholesterol in biliary endoprosthesis using gas chromatography-mass spectrometry (GC-MS). A dual-arm robot performs both transport and active manipulation tasks to ensure human-like operation. This general robotic concept also enables the use of manual laboratory devices and equipment and is thus suitable in areas with a high standardization grade. PMID- 27000133 TI - Treatment of Chronic Achilles Tendon Ruptures With Large Defects. AB - Background When Achilles tendon ruptures become chronic, a defect often forms at the rupture site. There is scant literature regarding the treatment of chronic Achilles ruptures with defects of 6 cm or larger. We examined outcomes from combining a turndown of the proximal, central Achilles with a flexor hallucis longus (FHL) tendon transfer to treat this condition. Materials Between September 2002 and December 2013, 32 patients presented with a chronic Achilles rupture and a defect of 6 cm or more. Twenty patients were male and 12 were female. Patient age was between 20 and 74 years, with a mean of 53.3 years. Eighteen and 14 patients had their right and left Achilles tendon affected, respectively. The number of days between injury and surgery ranged from 30 to 315 days, with a mean of 102 days. Reconstruction of the Achilles involved a turndown of the proximal, central tendon and FHL augmentation. Final patient follow-up ranged from 18 to 150 months, with a mean of 62.3 months. RESULTS: At surgery, the gap between the ruptured ends of the Achilles ranged from 6 to 12 cm, with a mean gap of 7.5 cm. Full healing was achieved in all 32 patients (100%) by 5 months postoperatively. Mean Foot and Ankle Ability Measures scores increased from 36.3% to 90.2% between initial and latest follow-up (P < .05). Mean visual analogue scales of pain decreased from 6.6 to 1.8 of 10 between first and last encounter (P < .05). Postoperative complications occurred in 5 patients (15.6%), including 3 (9.4%) superficial wound problems, 1 (3.1%) deep wound infection, and 1 (3.1%) deep vein thrombosis. Discussion Outcomes from treating chronic Achilles ruptures with large defects are scant within the orthopaedic literature. Our method of Achilles reconstruction results in a high rate of improved function and pain relief. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case series. PMID- 27000134 TI - Recommodification, Unemployment, and Health Inequalities: Trends in England and Sweden 1991-2011. AB - Recommodification, the withdrawal of social welfare, has been going on for some decades in both Sweden and England. Recommodification disproportionately affects the unemployed because of their weak market position. We investigated the impact recommodification has had on health inequalities between the employed and unemployed in Sweden and England. Using national surveys, odds ratios for the likelihood of reporting less than good health between the employed and unemployed were computed annually between 1991 and 2011. The correlation between these odds ratios and net replacement rates was then examined. Health inequalities between the employed and unemployed were greater in 2011 than in 1991 in both countries. Sweden began with smaller health inequalities, but by 2011, they were in line with those in England. Sweden experienced more recommodification than England during this period, although it started from a much less commodified position. Correspondingly, correlation between unemployment benefit generosity and health inequalities was stronger in Sweden than in England. Recommodification is linked to ill health among the unemployed and to the health gap between the employed and unemployed. We propose that further recommodification will be associated with increased health inequalities between the employed and unemployed. PMID- 27000135 TI - Consumer perceptions, descriptive profile, and mechanical properties of a novel product with chickpea flour: Effect of ingredients. AB - Increasingly popular in the West is hummus, a spread that is made with pureed chickpeas and other healthful ingredients. The changes in texture measurements and sensory properties in a novel chickpea flour-based product occurring when water is partially replaced by common ingredients of hummus were investigated. Eleven chickpea gels containing different amounts of minced garlic, lemon juice, curry powder, and inulin were prepared and compared with two control gels. These ingredients were chosen to make the product tastier, appealing, and similar to hummus. Instrumental texture tests were carried out: uniaxial compression, stress relaxation, and texture profile analysis. Quantitative descriptive analysis was used to describe differences in sensory properties perceived by a trained panel, whereas repertory grid method combined with free choice profile was used to determine differences perceived by untrained consumers. Gels with higher curry powder content presented lower force to breakdown, whereas increasing inulin content led to gels with higher hardness. Principal component analysis was applied to instrumental parameters and quantitative descriptive analysis data, whereas generalized Procrustes analysis was applied to free choice profile data. This newly developed chickpea gel may make a nutrition claim with respect to protein ("high in protein," or at least a "source of protein"). PMID- 27000136 TI - Healthism in Denmark: State, market, and the search for a "Moral Compass". AB - This article focuses on contemporary responses to public health messages in Denmark, a country whose system of social welfare is, like that of the United Kingdom and the rest of Europe, undergoing increasing levels of marketization and privatization. Drawing primarily upon Robert Crawford's analysis of healthism as a neoliberal project, the aim of this article is to develop critical understandings of how individuals respond both bodily and emotionally to ideologies of health and the body in the context of a changing marketplace for the consumption of health and its messages. This article will analyze perceptions and practices of health in Denmark. The findings will then be discussed in relation to dimensions inspired by the work of Crawford, who regards "health" as a "super-value," an outcome of individual security strategies, and mode of citizenship in the marketplace. The article argues that Crawford's discussion does not fully capture the ways in which people use their bodies to valorize themselves. First, the perception of the state is perceived as being aligned with commercial interests. As a consequence, neither state- nor market-based (i.e. commercial health product and service providers) health advice is fully trusted. Instead, the opinions of non-market actors such as peers and friends as well as of alternative practitioners that are considered outside the market since they do not represent corporate interests become more attractive among citizen-consumers who are concerned about their health. The article concludes with a discussion of the implications of our findings for theorization of public health and health policy. PMID- 27000137 TI - Cangrelor Bridge Therapy for Gastroduodenal Biopsy. AB - Dual antiplatelet therapy (DAPT) is the key for secondary prevention of acute coronary syndromes and percutaneous coronary intervention with stent placement. Premature discontinuation of DAPT can result in an increase in cardiac ischemic events and death. If early interruption of DAPT for urgent procedures or surgery is necessary, then ischemic and bleed risks must be balanced with bridging therapy. To date, no medications have a Food and Drug Administration indication for antiplatelet bridge therapy. We present a case of a woman with a history of gastrointestinal bleeding on DAPT for a drug-eluting stent who received cangrelor as bridge therapy prior to gastroduodenal biopsy. PMID- 27000138 TI - Pharmacist Involvement in a Community Paramedicine Team. AB - BACKGROUND: Hospital readmissions have recently gained scrutiny by health systems as a result of their high costs of care and potential for financial penalty in hospital reimbursement. Mobile-integrated health and community paramedicine (MIH CP) programs have expanded to serve patients at high risk of hospital readmission. Pharmacists have also improved clinical outcomes for patients during in-home visits. However, pharmacists working with a MIH-CP program have not been previously described. This project utilized a novel multidisciplinary Community Paramedicine Team (CPT) consisting of a pharmacist, paramedic, and social worker to target patients with heart failure at high risk of readmission to assist with coordination of care and education. OBJECTIVES: This article describes the development of the CPT, delineation of CPT member responsibilities, and outcomes from pilot visits. METHODS: The CPT visited eligible patients in their homes to provide services. Patients with heart failure who were readmitted within 30 days were eligible for a home visit. RESULTS: A total of 6 patients were seen during the pilot, and 2 additional patients were seen after the pilot. CONCLUSION: Imbedding a pharmacist into a CPT provides a unique expansion of pharmacy services and a novel approach to address hospital readmissions. PMID- 27000139 TI - Moxifloxacin-Induced Visual Hallucinations: A Case Report and Review of the Literature. AB - Fluoroquinolones are extensively used to treat a variety of common bacterial infections. Due to their extensive use in clinical practice, increases in neuropsychiatric events have been reported. We discuss the case of a young female who developed visual hallucinations after 2 doses of moxifloxacin. After discontinuation of the moxifloxacin, the patient's symptoms completely resolved. While one other case report exists with moxifloxacin, this case is unique in comparison. Our patient was a young female with no kidney dysfunction, no drug abuse history, absence of polypharmacy, and no previous psychological history that would have put her at an increased risk of drug-induced psychosis. Due to the prevalence of medication-induced hallucinations, it is imperative that clinicians are able to recognize offending medications in an effort to prevent misdiagnosis of a psychiatric illness. PMID- 27000140 TI - What Does Success Look Like in the Forensic Mental Health System? Perspectives of Service Users and Service Providers. AB - Outcomes research in forensic mental health (FMH) has concentrated on reoffending as the principal indicator of success. Defining success in one-dimensional, negative terms can create a distorted view of the diverse objectives of the FMH system. This qualitative study examined the complexity of success from the perspectives of people in the FMH system. Interviews were conducted with 18 forensic service users and 10 forensic service providers. Data were analyzed inductively using thematic analysis to identify predominant themes. The participants conceptualized success as a dynamic process materializing across six different domains in the context of the FMH system: (a) normal life, (b) independent life, (c) compliant life, (d) healthy life, (e) meaningful life, and (f) progressing life. The results indicate that people who provide or use FMH services emphasize a broad range of processes and outcomes, apart from public safety, when they think about success. PMID- 27000141 TI - Homeless Shelters' Policies on Sex Offenders: Is This Another Collateral Consequence? AB - The primary focus of sex offender research has been on the efficacy and collateral consequences of sex offender registration and notification (SORN) and residence restrictions. Past scholarship has found these laws to cause numerous re-entry barriers for sex offenders. Such barriers have affected sex offenders' ability to find and maintain housing, employment, and social support. Moreover, registered sex offenders (RSOs) have become homeless due to such laws. Although previous scholarship has highlighted the collateral consequences of SORN, there is a lack of scholarship addressing homeless sex offenders. Specifically, the current study assesses policies regarding RSO access to homeless shelters in a four-state region, focusing on the effect of structural, procedural, and geographic factors, as well as a shelter's proximity to children. Drawing on the loose coupling organizational framework, the findings suggest that a small maximum occupancy, unwritten policies for RSOs, being in Kentucky or Tennessee, being located near a school, and being near a higher proportion of homes with children all decrease the odds that a homeless shelter allows RSOs. Furthermore, although unwilling to make exceptions to the policies regarding RSOs, shelters were generally willing to make exceptions to other policies governing shelter accessibility. PMID- 27000142 TI - Prospective study on cost-effectiveness of home-based motor assessment in Parkinson's disease. AB - Introduction Treatment adjustments in Parkinson's disease (PD) are in part dependent on motor assessments. The aim of this study was to evaluate the cost effectiveness of home-based motor monitoring plus standard in-office visits versus in-office visits alone in patients with advanced PD. Methods The procedures consisted of a prospective, one-year follow-up, randomized, case control study. A total of 40 patients with advanced PD were randomized into two groups: 20 patients underwent home-based motor monitoring by using wireless motion sensor technology, while the other 20 patients had in-office visits. Motor and non-motor symptom severities, quality of life, neuropsychiatric symptoms, and comorbidities were assessed every four months. Direct costs were assessed using a standardized questionnaire. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER). Results Both groups of PD patients were largely comparable in their clinical and demographic variables at baseline; however, there were more participants using levodopa-carbidopa intestinal gel in the home based motor monitoring group. There was a trend for lower Unified Parkinson's Disease Rating Scale functional status (UPDRS II) scores in the patients monitored at home compared to the standard clinical follow-up ( p = 0.06). However, UPDRS parts I, III, IV and quality-adjusted life-years scores were similar between both groups. Home-based motor monitoring was cost-effective in terms of improvement of functional status, motor severity, and motor complications (UPDRS II, III; IV subscales), with an ICER/UPDRS ranging from ?126.72 to ?701.31, respectively. Discussion Home-based motor monitoring is a tool which collects cost-effective clinical information and helps augment health care for patients with advanced PD. PMID- 27000143 TI - Seeking Male Sexual Partners via Internet and Traditional Venues among Chinese Men Who Have Sex with Men: Implications for HIV Risk Reduction Interventions. AB - The dynamic nature of finding male sexual partners (sex-finding) among Chinese men who have sex with men (MSM) may play a substantial role in the HIV epidemic. We compared characteristics and behaviors of MSM who mostly sought sex via the Internet versus traditional venues in a cross-sectional survey among 3588 Chinese MSM. We assessed the sociodemographic predictors and compared high-risk behaviors of using Internet versus traditional venues for sex-finding. Compared to non Internet MSM, Internet-user MSM were more likely to have been: younger, currently single, better educated, health-insured, with higher income, with Beijing residency ('Hukou'), living longer in the city, HIV-positive, ever using drug and engaging in condomless receptive anal sex. Internet sex-finding users were less likely to be sexually active for longer duration, drink alcohol, drink alcohol before sex, or ever have sex with women. Knowledge of differential characteristics of various sex-finding MSM can help design targeted interventions. PMID- 27000144 TI - Effects of a Pilot Church-Based Intervention to Reduce HIV Stigma and Promote HIV Testing Among African Americans and Latinos. AB - HIV-related stigma and mistrust contribute to HIV disparities. Addressing stigma with faith partners may be effective, but few church-based stigma reduction interventions have been tested. We implemented a pilot intervention with 3 Latino and 2 African American churches (4 in matched pairs) in high HIV prevalence areas of Los Angeles County to reduce HIV stigma and mistrust and increase HIV testing. The intervention included HIV education and peer leader workshops, pastor delivered sermons on HIV with imagined contact scenarios, and HIV testing events. We surveyed congregants at baseline and 6 month follow-up (n = 1235) and found statistically significant (p < 0.05) reductions in HIV stigma and mistrust in the Latino intervention churches but not in the African American intervention church nor overall across matched African American and Latino pairs. However, within matched pairs, intervention churches had much higher rates of HIV testing (p < 0.001). Stigma reduction and HIV testing may have synergistic effects in community settings. PMID- 27000146 TI - Upper extremity deep vein thrombosis - The venous thromboembolism Cinderella? PMID- 27000145 TI - Familiarity with and Preferences for Oral and Long-Acting Injectable HIV Pre exposure Prophylaxis (PrEP) in a National Sample of Gay and Bisexual Men in the U.S. AB - We sought to determine preferences for oral versus long-acting injectable (LAI) PrEP among gay and bisexual men (GBM). We surveyed a national U.S. sample of 1071 GBM about forms of PrEP. LAI PrEP was found to be acceptable among 43.2 % of men when injected monthly compared with 53.6 % of men when injected every 3 months. When asked to choose between forms of PrEP, 46.0 % preferred LAI, 14.3 % oral, 21.7 % whichever was most effective, 10.1 % had no preference, and 7.8 % would not take PrEP. There were no differences in PrEP preferences by race/ethnicity, income, region of residence, or relationship status. Those unwilling to take PrEP were significantly older than those who preferred LAI PrEP and those who would take either. Those who preferred the most effective form were younger, had less education, and reported more recent club drug use. Those who reported condomless anal sex and those who thought they were good PrEP candidates were more willing to take PrEP. Long-term health and side effects were of the greatest concern for both LAI and oral PrEP. The availability of LAI PrEP has the potential to increase uptake among GBM. The results of ongoing clinical trials of LAI PrEP will need to demonstrate similar or greater efficacy as daily Truvada for uptake to be maximized. PMID- 27000147 TI - Measurement resources for dissemination and implementation research in health. AB - BACKGROUND: A 2-day consensus working meeting, hosted by the United States National Institutes of Health and the Veterans Administration, focused on issues related to dissemination and implementation (D&I) research in measurement and reporting. Meeting participants included 23 researchers, practitioners, and decision makers from the USA and Canada who concluded that the field would greatly benefit from measurement resources to enhance the ease, harmonization, and rigor of D&I evaluation efforts. This paper describes the findings from an environmental scan and literature review of resources for D&I measures. FINDINGS: We identified a total of 17 resources, including four web-based repositories and 12 static reviews or tools that attempted to synthesize and evaluate existing measures for D&I research. Thirteen resources came from the health discipline, and 11 were populated from database reviews. Ten focused on quantitative measures, and all were generated as a resource for researchers. Fourteen were organized according to an established D&I theory or framework, with the number of constructs and measures ranging from 1 to more than 450. Measure metadata was quite variable with only six providing information on the psychometric properties of measures. CONCLUSIONS: Additional guidance on the development and use of measures are needed. A number of approaches, resources, and critical areas for future work are discussed. Researchers and stakeholders are encouraged to take advantage of a number of funding mechanisms supporting this type of work. PMID- 27000148 TI - Facilitators and Barriers of Implementing a Measurement Feedback System in Public Youth Mental Health. AB - This study examines implementation facilitators and barriers of a statewide roll out of a measurement feedback system (MFS) in a youth public mental health system. 76 % of all state care coordinators (N = 47) completed interviews, which were coded via content analysis until saturation. Facilitators (e.g., recognition of the MFS's clinical utility) and barriers (e.g., MFS's reliability and validity) emerged paralleling the Exploration, Adoption/Preparation, Implementation, and Sustainment framework outlined by Aarons et al. (Adm Policy Mental Health Mental Health Serv Res, 38:4-23, 2011). Sustainment efforts may leverage innovation fit, individual adopter, and system related facilitators. PMID- 27000150 TI - Circulating non-hematological cells during cardiopulmonary bypass: new findings in cardiac surgery procedures. AB - BACKGROUND: Several factors have been historically advocated to explain the coagulative and inflammatory disorders following cardiopulmonary bypass (CPB). In this paper, we describe the presence of circulating non-hematological cells, introduced within the bloodstream during CPB. We defined the origin of the cells and tested their impact on coagulation. METHODS: We collected peripheral arterial blood samples in twenty consecutive coronary artery bypass graft cases at four different surgical moments and assessed the presence and nature of circulating cells with the use of the CELLSEARCH(r) Test, immunocytochemistry and immunofluorescence, evaluating the expression of cytokeratin and calretinin. The effect of the circulating non-hematological cells on coagulation was tested in vitro, using the ROTEM assay. RESULTS: A mean of 263.85 +/- 57.5 (median 258.5) cells were present in the samples following the suction of blood from the surgical field while all the other samples were negative (zero cells) (p<0.00001). Immunologic tests confirmed the mesothelial origin of the cells. The ROTEM(r) assay of the blood samples contaminated by the mesothelial cells presented longer clotting times (53.4 +/- 8.2 secs 48.3 +/- 8.9 sec, p=0.05), longer clot formation times (137.1 +/- 31.5 sec vs 111.9 +/- 25.2 sec, p=0.009), smaller alfa angle amplitudes (66.7 +/- 9.1 degrees vs 71.1 +/- 5.1 degrees , p=0.04) and maximum clot firmness times (59.0 +/- 5.4 sec vs 61.9 +/-4.6 sec, p=0.004) than the controls. CONCLUSION: The presence of circulating non hematological cells during CPB with a mesothelial immunophenotype alters in vitro coagulation assays. This finding can help to further understand the pathophysiology of CPB. PMID- 27000149 TI - Predictors of activity level and retention among African American lay health advisors (LHAs) from The National Witness Project: Implications for the implementation and sustainability of community-based LHA programs from a longitudinal study. AB - BACKGROUND: Lay health advisor (LHA) programs are increasingly being implemented in the USA and globally in the context of health promotion and disease prevention. LHAs are effective in addressing health disparities when used to reach medically underserved populations, with strong evidence among African American and Hispanic women. Despite their success and the evidence supporting implementation of LHA programs in community settings, there are tremendous barriers to sustaining LHA programs and little is understood about their implementation and sustainability in "real-world" settings. The purpose of this study was to (1) propose a conceptual framework to investigate factors at individual, social, and organizational levels that impact LHA activity and retention; and (2) use prospective data to investigate the individual, social, and organizational factors that predict activity level and retention among a community-based sample of African American LHAs participating in an effective, evidence-based LHA program (National Witness Project; NWP). METHODS: Seventy-six LHAs were recruited from eight NWP sites across the USA. Baseline predictor data was collected from LHAs during a telephone questionnaire administered between 2010 and 2011. Outcome data on LHA participation and program activity levels were collected in the fall of 2012 from NWP program directors. Chi-square and ANOVA tests were used to identify differences between retained and completely inactive LHAs, and LHAs with high/moderate vs. low/no activity levels. Multivariable logistic regression models were conducted to identify variables that predicted LHA retention and activity levels. RESULTS: In multivariable models, LHAs based at sites with academic partnerships had increased odds of retention and high/moderate activity levels, even after adjusting for baseline LHA activity level. Higher religiosity among LHAs was associated with decreased odds of being highly/moderately active. LHA role clarity and self-efficacy were associated with retention and high/moderate activity in multivariable models unadjusted for baseline LHA activity level. CONCLUSIONS: Organizational and role-related factors are critical in influencing the retention and activity levels of LHAs. Developing and fostering partnerships with academic institutions will be important strategies to promote successful implementation and sustainability of LHA programs. Clarifying role expectations and building self-efficacy during LHA recruitment and training should be further explored to promote LHA retention and participation. PMID- 27000151 TI - Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1. AB - Ischemia reperfusion (IR) injury (IRI) is associated with poor prognoses in the settings of both cardiac surgery and ischemic heart disease and causes mitochondrial oxidative stress and cell death. Silent information regulator 1 (SIRT1), a member of the histone deacetylase family, exerts anti-IRI effects. Bakuchiol (BAK), an analog of resveratrol and a monoterpene phenol isolated from the seeds of Psoralea corylifolia (Leguminosae), protects tissues from injury. This study was designed to investigate the protective effects of BAK treatment in the setting of myocardial IRI and to elucidate the potential mechanism of those effects. Prior to induction of IR, isolated rat hearts or cardiomyocytes were exposed to BAK in either the absence or presence of the SIRT1 inhibitors Sirtinol and SIRT1 siRNA. BAK exerted cardioprotective effects, as evidenced by the improvements noted in cardiac function following ischemia, attenuated myocardial apoptosis, and changes in several biochemical parameters (including increases in the level of the anti-apoptotic protein Bcl2, decreases in the level of the pro apoptotic protein Bax, and decreases in the cleaved Caspase 3 level). However, Sirtinol and SIRT1 siRNA each blocked BAK-induced cardioprotection by inhibiting SIRT1 signaling. Additionally, BAK significantly increased the activities of mitochondrial succinate dehydrogenase, cytochrome c oxidase, and mitochondrial superoxide dismutase and decreased the production of malondialdehyde. These findings suggested that BAK significantly attenuated IR-induced mitochondrial oxidative damage. However, Sirtinol and SIRT1 siRNA abolished BAK-dependent mitochondrial function. In summary, our results demonstrate that BAK treatment attenuates IRI by attenuating IR-induced mitochondrial oxidative damage via the activation of SIRT1/PGC-1alpha signaling. PMID- 27000152 TI - Understanding cancer networks better to implement them more effectively: a mixed methods multi-case study. AB - BACKGROUND: Managed cancer networks are widely promoted in national cancer control programs as an organizational form that enables integrated care as well as enhanced patient outcomes. While national programs are set by policy-makers, the detailed implementation of networks is delegated at the service delivery and institutional levels. It is likely that the capacity to ensure more integrated cancer services requires multi-level governance processes responsive to the strengths and limitations of the contexts and capable of supporting network-based working. Based on an empirical case, this study aims to analyze the implementation of a mandated cancer network, focusing on governance and health services integration as core concepts in the study. METHODS/DESIGN: This nested multi-case study uses mixed methods to explore the implementation of a mandated cancer network in Quebec, a province of Canada. The case is the National Cancer Network (NCN) subdivided into three micro-cases, each defined by the geographic territory of a health and social services region. For each region, two local health services centers (LHSCs) are selected based on their differences with respect to determining characteristics. Qualitative data will be collected from various sources using three strategies: review of documents, focus groups, and semi-directed interviews with stakeholders. The qualitative data will be supplemented with a survey that will measure the degree of integration as a proxy for implementation of the NCN. A score will be constructed, and then triangulated with the qualitative data, which will have been subjected to content analysis. Qualitative, quantitative, and mixed methods data will be interpreted within and across cases in order to identify governance patterns similarities and differences and degree of integration in contexts. DISCUSSION: This study is designed to inform decision-making to develop more effective network implementation strategies by thoroughly describing multi-level governance processes of a sample of settings that provide cancer services. Although the study focuses on the implementation of a cancer network in Quebec, the rich descriptions of multiple nested cases will generate data with a degree of generalizability for health-care systems in developed countries. PMID- 27000153 TI - The rate of and risk factors for frequent hospitalization in systemic lupus erythematosus: results from the Korean lupus network registry. AB - Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined "frequent hospitalization" as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8 year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjogren's syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjogren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and arthritis, pericarditis, and anti-Sjogren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. PMID- 27000154 TI - Impaired diffusion tensor imaging findings in the corpus callosum and cingulum may underlie impaired learning and memory abilities in systemic lupus erythematosus. AB - BACKGROUND: Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, its pathogenesis is unknown. In a previous functional magnetic resonance imaging (fMRI) study we demonstrated altered brain activity dynamics and less brain deactivation in patients with SLE as compared with healthy controls, when performing a learning and memory task. Our findings localized this impairment to the default mode network (DMN), and particularly to its anterior medial prefrontal cortex node. In addition, altered networking of the hippocampal subsystem of the DMN was seen in patients with SLE when performing this task, as well as atrophy of the left hippocampus. The present study aimed to search for a structural substrate for the altered recruitment pattern observed in fMRI studies using diffusion tensor imaging (DTI). PATIENTS AND METHODS: Using DTI, we characterized brain diffusivity in 10 patients with SLE and nine healthy controls. Two tracts associated with the DMN were reconstructed: the corpus callosum (CC) and the cingulum bundle. The CC was segmented according to the Witelson segmentation scheme and the cingulum was segmented into superior and descending bundles. RESULTS: A significant increase in mean diffusivity (MD) was seen in patients with SLE without neuropsychiatric SLE (NPSLE) as compared with healthy controls in all five segments of the CC (segment 1: p = 0.043; segment 2: p = 0.005; segment 3: p = 0.003; segment 4: p = 0.012; segment 5: p = 0.023) as well as in the descending portion of the left cingulum bundle (p = 0.026). CONCLUSIONS: Increased MD values in the CC and the left cingulum may indicate impaired organization/reduced integrity of these tracts, which may underlie the abnormal pattern of brain activity recruitment of the DMN observed during a verbal learning and memory task. Taking into account the central role of the left hippocampus in verbal memory, the abnormal integrity of the left cingulum may contribute to the reduced performance of patients with SLE on verbal memory tasks. PMID- 27000155 TI - Mediators of the Relation Between Community Violence and Sexual Risk Behavior Among Adults Attending a Public Sexually Transmitted Infection Clinic. AB - Prior research shows that violence is associated with sexual risk behavior, but little is known about the relation between community violence (i.e., violence that is witnessed or experienced in one's neighborhood) and sexual risk behavior. To better understand contextual influences on HIV risk behavior, we asked 508 adult patients attending a publicly funded STI clinic in the U.S. (54 % male, M age = 27.93, 68 % African American) who were participating in a larger trial to complete a survey assessing exposure to community violence, sexual risk behavior, and potential mediators of the community violence-sexual risk behavior relation (i.e., mental health, substance use, and experiencing intimate partner violence). A separate sample of participants from the same trial completed measures of sexual behavior norms, which were aggregated to create measures of census tract sexual behavior norms. Data analyses controlling for socioeconomic status revealed that higher levels of community violence were associated with more sexual partners for men and with more episodes of unprotected sex with non-steady partners for women. For both men and women, substance use and mental health mediated the community violence-sexual risk behavior relation; in addition, for men only, experiencing intimate partner violence also mediated this relation. These results confirm that, for individuals living in communities with high levels of violence, sexual risk reduction interventions need to address intimate partner violence, substance use, and mental health to be optimally effective. PMID- 27000156 TI - Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. AB - With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22,774 and 84,572 annually. Rates of extended-spectrum beta-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies. PMID- 27000157 TI - Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but Not overall survival in patients with salivary gland adenoid cystic carcinoma-a propensity score matched study. AB - PURPOSE: To compare the long-term outcomes in patients with salivary gland adenoid cystic carcinoma (SGACC) treated with post-operative chemoradiotherapy (POCRT) versus post-operative radiotherapy (PORT). METHODS: We retrospectively reviewed the records of 91 SGACC patients treated with surgery followed by PORT (n = 58) or POCRT (n = 33) between 2000 and 2013. Treatment outcomes between groups were compared using propensity score matching (1:1 nearest neighbor). RESULTS: The median radiation dose was 66 Gy, and patients were followed up for a median of 71 months. Cisplatin-based concurrent regimens were the most commonly used chemotherapy schedules. In the entire study cohort, patients undergoing POCRT showed a trend toward higher locoregional control (LRC) rates than those treated with PORT alone at both 5 and 8 years (97 and 97 % versus 84 and 79 %, respectively; P = .066). Distant metastases were the most common form of treatment failure and occurred in 31 (34 %) patients (PORT, n = 17; POCRT, n = 14). After propensity score matching (33 pairs), patients receiving POCRT had 5- and 8 year LRC rates of 97 and 97 %, respectively, compared with 79 and 67 % for patients treated with PORT alone (P = .017). The two groups did not differ significantly in terms of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). However, a significantly better opioid requiring pain-free survival (ORPFS) was achieved in POCRT group (P = .038). Subgroup analyses revealed that patients with stage III - IV disease (P = .040 and .017), positive surgical margins (P = .011 and .050), or perineural invasion (P = .013 and .035) had significantly higher 5- and 8 year LRC and ORPFS when treated with POCRT, respectively. CONCLUSIONS: In SGACC patients, adding concurrent chemotherapy to PORT may increase LRC and ORPFS rates, particularly in presence of stage III - IV disease, positive surgical margins, or perineural invasion. However, no significant differences in DMFS, DFS, and OS were observed. PMID- 27000161 TI - Standardized patients' preferences for pharmacist interactive communication style: A mixed method approach. AB - BACKGROUND: Interactive communication approaches may help to shift pharmacy practice toward more patient-centered care. One example of such an approach is the 3 prime questions (3PQs). Patients' preferences for pharmacists' interactive communication styles were not identified in the literature. OBJECTIVE: The purpose of this paper was to explore standardized patient (SP) preferences, satisfaction, and perceptions of pharmacists' communication style and changes in pharmacist to standardized patient talk-time ratio. DESIGN: Mixed methods, before and after evaluation. SETTING: SPs were hired from the University of Alberta's Standardized Patient Program, Canada. PARTICIPANTS: Twelve SPs and 10 pharmacists. INTERVENTION: SPs were video recorded interacting with the same pharmacists before and after pharmacist training on the 3PQs. SPs participated in an open-ended interview using stimulated recall on videos of their pharmacist encounters. MAIN OUTCOME MEASURES: Explore SP preferences, satisfaction, and perceptions of pharmacists' communication style, in addition to changes in pharmacist to standardized patient talk-time ratio before and after the intervention RESULTS: Generally SPs were satisfied with pharmacists' interactive communication style post training. Qualitative themes varied with SPs' preference for an interactive approach (58%, i.e., Conversation with Equals, Double Check, and Manageable Information) or traditional approach (33%, i.e., Expected Information, Shouldn't the Pharmacist Know, and Feels Uncomfortable) and improvements in item scores varied by type of prescription. Pharmacists' use of the 3PQs increased patient talk time for scenarios with new chronic and acute medication, though pharmacists still dominated the conversation. CONCLUSION: Just over half of SPs preferred an interactive communication style, although a third of SPs preferred a communication style that focused on information provision. Patients had more time to talk in some interactive encounters. Pharmacists may need to be aware of patient expectations when using the 3PQs. PMID- 27000162 TI - Smoking quit rates among patients receiving pharmacist-provided pharmacotherapy and telephonic smoking cessation counseling. AB - OBJECTIVES: Tobacco use is the nation's leading cause of preventable illness and death, causing a significant burden on the health care system. Many cessation pharmacotherapy treatment options are available to help smokers quit, including nicotine replacement therapies (NRTs) and prescription medications. Research indicates that pharmacists are able to provide a positive benefit to smokers who want to quit through pharmacologic and nonpharmacologic interventions. The aim of the present work was to examine the quit rates among participants who received smoking cessation pharmacotherapy and pharmacist-provided telephone-based quit counseling services. DESIGN: Retrospective database review of enrolled participants. SETTING: Telephone-based pharmacotherapy and medication counseling services offered from a medication management center. PARTICIPANTS: State employees who voluntarily contacted a medication management center for smoking cessation services after receiving promotional flyers. MAIN OUTCOME MEASURES: Long-term quit rates at 7 and 13 months were determined by means of patient self report in response to questioning. Smoking cessation was considered to be a success if the patient reported not smoking for the past 30 days. RESULTS: A total of 238 participants were included in the review. Thirty-nine participants completed the program after the first treatment, 12 participants after the second treatment, and 4 participants after the third treatment. Two patients completed the program more than once. Eighty-five participants (36%) reported results at 7 month follow-up; of these, 43 (51%) were smoking free. A total of 44 participants (18%) reported results at 13-month follow-up; of these, 24 participants (55%) reported being smoking free. There were no significant differences in the percentages of smoking-free participants at 7 or 13 months, regardless of their first treatment (P = 0.06 and 0.345, respectively). CONCLUSION: Successful quit rates were higher than previously demonstrated with other telephone-based smoking cessation programs. Therefore, pharmacist-provided telephone-based counseling may be beneficial in helping patients to quit smoking. Future research is warranted to examine the benefits of these types of programs. PMID- 27000163 TI - Appropriateness of oral medication delivery devices available in community pharmacies. AB - OBJECTIVES: To identify the proportion of prescribed liquid medications that can be properly administered with devices available at local community pharmacies. METHODS: Prescriptions written over a 2-month time frame in a pediatric clinic were analyzed and compared with measuring devices available at community pharmacies within a 5-mile radius. Devices from the pharmacies were compared with the prescriptions to determine if they were acceptable and/or optimal to measure the dose as prescribed. Data collected for each prescription included items such as presence of markings on the device at the prescribed dose, if the units of measurement matched the device, if acceptable to measure the prescribed volume with the available device, optimal syringe volume, and if the pharmacy had an optimal device for the prescribed volume. RESULTS: Among the 11 different devices collected from the pharmacies, 5 different types were found. Over the 2 months of prescription data analyzed, 557 prescriptions were written, with 158 (28%) being liquids requiring a medication delivery device for administration. When comparing the 5 unique devices to 158 prescriptions independently, it was found that 9%, 30%, 53%, and 92%, respectively, for the 1-mL, 3-mL, 5-mL, and 10-mL devices were acceptable to measure the volume prescribed. The 5-mL syringe was optimal in only 21% of prescriptions analyzed, and the 10-mL syringe and spoon were found to be the most optimal device for the prescriptions analyzed. Of the 5 pharmacies reviewed, all prescriptions could be optimally measured with the use of devices that they had available 49% of the time (range 22% to 78%). CONCLUSION: Oral medication delivery devices are imperative for safe and effective oral liquid medication use. Understanding optimal and acceptable devices would allow pharmacists to tailor patient-specific education and would allow direction when stocking oral delivery devices in the community pharmacy. PMID- 27000164 TI - Pharmacists' perceived knowledge of and confidence in dispensing oral antineoplastic agents. AB - OBJECTIVES: To assess community pharmacists' perceived confidence with counseling patients about oral antineoplastic agents, in identifying drug and/or herbal interactions with these agents, and with identifying adverse drug events. METHODS: Four hundred pharmacists were contacted and asked to take an anonymous survey regarding 11 oral antineoplastic agents (OAAs) and the oral antineoplastic market place in general. RESULTS: With a response rate of 61.5%, there was variation with perceived overall confidence in counseling patients, identifying drug and/or herbal interactions (DHIs), and identifying adverse drug events (ADEs) with each oral antineoplastic agent (OAA). There was a trend toward more confidence in identifying DHI and ADE in those agents dispensed within the past 6 months. The majority of pharmacists reported the main barrier to counseling to be a lack of training or knowledge. Only about 22% of pharmacists who participated in this survey reported confidence in their ability to manage an influx of OAAs. CONCLUSION: Overall, there was a lack of perceived confidence among pharmacists in counseling patients and identifying DHIs as well as with identifying ADEs with the 11 OAAs chosen for this survey. One of the main barriers identified was the lack of knowledge or training. These data provide preliminary information needed to launch educational programs in the student pharmacist curriculum (e.g., elective courses) and continuing education programs to improve overall confidence among pharmacists. PMID- 27000166 TI - Vaccination resources for health care providers. AB - OBJECTIVE: To create a quick information evaluation tool (QIET) for judging the quality of online vaccination information sources. SETTING: This information is intended to be used in a retail or a community pharmacy setting where immunizations are provided. PRACTICE: The tool created can be used by immunization providers and patients to evaluate online sources of vaccination information. DESCRIPTION: The tool is the result of a consensus from surveyed websites that provide ways to evaluate the reliability of online information. These websites were highlighted as reliable resources in the American Pharmacists Association's (APhA) Immunization Handbook. PRACTICE INNOVATION: Several websites provide ways to evaluate the reliability of online vaccine information; however, none were found that provided a consensus from several websites and examples of how to evaluate online information. This tool provides that consensus. INTERVENTIONS: This tool provides a way to judge the merits of online immunization information using a single set of useful criteria in place of various criteria listed in many different sources. EVALUATION: This tool will be successful if immunization providers and patients can use it to choose reliable sources of online vaccination information. RESULTS: Using the QIET, several non APhA sources are evaluated. CONCLUSION: The QIET is a potential resource that can be used by future studies to evaluate the reliability of online vaccine information. PMID- 27000165 TI - Trained student pharmacists' telephonic collection of patient medication information: Evaluation of a structured interview tool. AB - OBJECTIVE: To determine the feasibility and fidelity of student pharmacists collecting patient medication list information using a structured interview tool and the accuracy of documenting the information. The medication lists were used by a community pharmacist to provide a targeted medication therapy management (MTM) intervention. DESIGN: Descriptive analysis of patient medication lists collected with telephone interviews. PARTICIPANTS: Ten trained student pharmacists collected the medication lists. INTERVENTION: Trained student pharmacists conducted audio-recorded telephone interviews with 80 English speaking, community-dwelling older adults using a structured interview tool to collect and document medication lists. MAIN OUTCOME MEASURES: Feasibility was measured using the number of completed interviews, the time student pharmacists took to collect the information, and pharmacist feedback. Fidelity to the interview tool was measured by assessing student pharmacists' adherence to asking all scripted questions and probes. Accuracy was measured by comparing the audio recorded interviews to the medication list information documented in an electronic medical record. RESULTS: On average, it took student pharmacists 26.7 minutes to collect the medication lists. The community pharmacist said the medication lists were complete and that having the medication lists saved time and allowed him to focus on assessment, recommendations, and education during the targeted MTM session. Fidelity was high, with an overall proportion of asked scripted probes of 83.75% (95% confidence interval [CI], 80.62-86.88%). Accuracy was also high for both prescription (95.1%; 95% CI, 94.3-95.8%) and nonprescription (90.5%; 95% CI, 89.4-91.4%) medications. CONCLUSION: Trained student pharmacists were able to use an interview tool to collect and document medication lists with a high degree of fidelity and accuracy. This study suggests that student pharmacists or trained technicians may be able to collect patient medication lists to facilitate MTM sessions in the community pharmacy setting. Evaluating the sustainability of using student pharmacists or trained technicians to collect medication lists is needed. PMID- 27000167 TI - Shared decision making and medication therapy management with the use of an interactive template. AB - OBJECTIVES: To evaluate the preliminary efficacy, feasibility, and acceptability of a template-based intervention to facilitate shared decision making (SDM) in medication therapy management (MTM) consultations; and to examine the type and number of drug therapy problems (DTPs) discussed and how resolution was communicated to patients' primary care providers (PCPs). SETTING: An internal medicine clinic at a large safety-net hospital. PRACTICE DESCRIPTION: Hennepin County Medical Center is an urban safety net hospital serving an ethnically diverse population with about 50 percent of patients enrolled in Medicaid. Within its internal medicine clinic, the study setting, over 100 clinicians participate in the primary care of approximately 25,000 discrete patients. PRACTICE INNOVATION: This is the first study to use a template format to facilitate SDM with pharmacists in MTM consultations. The template approach is more flexible than the use of decision aids, facilitating discussion around various issues. INTERVENTIONS: Patients completed template-guided interventions with pharmacists trained in SDM. EVALUATION: We analyzed the electronic health record used during the intervention, as well as post-appointment surveys administered to patients and pharmacists, for indications of SDM efficacy, feasibility, and acceptability. RESULTS: Twenty patients and four pharmacists participated in the study. Free text comments demonstrated that both patients and pharmacists appreciated the intervention, although some pharmacists had concerns including consultation length and SDM applicability. On average, two DTPs were identified per consultation and were most commonly related to appropriate compliance (30% of DTPs), appropriate indication (26%), medication effectiveness (23%), and safety (21%). CONCLUSION: Using a template to facilitate SDM within MTM consultations appears to be effective, feasible, and acceptable. DTP identification exemplifies a potential application of template-guided SDM. These results will be used to inform future work refining the intervention and developing robust comparative analyses. PMID- 27000168 TI - Federal Bureau of Prisons clinical pharmacy program improves patient A1C. AB - OBJECTIVE: The Federal Bureau of Prisons (BOP) currently has over 13,000 patients with diabetes and has placed an emphasis on preventing and delaying the onset or progression of diabetes-related complications. In an ongoing effort to improve patient outcomes, BOP has implemented a nationwide, dynamic system of pharmacist delivered patient care services via pharmacist clinicians working under the auspices of a physician-pharmacist collaborative practice agreement (CPA). SETTING: The BOP Clinical Pharmacy Workgroup targets improved patient outcomes via oversight and support of institution pharmacist clinicians and physicians in establishing and maintaining physician-pharmacist CPAs. A primary emphasis is diabetes and the pharmacist-run clinic clinical outcomes data are presented. PRACTICE INNOVATION: Seventy (nearly one-half) of eligible BOP pharmacists at 37 institutions offer pharmacist-delivered patient care services via an approved CPA. In total, BOP has 111 active physician-pharmacist CPAs. MAIN OUTCOME MEASURES: Pharmacist-run diabetes clinic outcomes from 5 institutions have been reported to date. A total of 126 patients were enrolled. Patient's hemoglobin A1C, blood pressure, and LDL cholesterol level are measured before (i.e., when accepted in the diabetes clinic) and after pharmacist-delivered care has been provided. The pharmacist-run diabetes clinics reported an average baseline A1C of 10.6% and produced an average outcome decrease in A1C of 2.3% from baseline. RESULTS: Specific pharmacist clinic interventions found to have the greatest impact are: 1) timely medication adjustment when indicated to help patients meet outcome goals; and 2) timely follow-up after a change in therapy is made (often within 1-2 weeks) with continued medication adjustment when indicated until outcome goal is achieved. CONCLUSION: BOP pharmacists have become respected and trusted clinicians within the team medicine model. As demonstrated by the pharmacist-run diabetes clinic outcomes, pharmacist clinicians are a valued link to the improvement of patient outcomes in BOP. PMID- 27000169 TI - Integrating home-based medication therapy management (MTM) services in a health system. AB - OBJECTIVES: To describe the integration of home-based Medication Therapy Management (MTM) into the ambulatory care infrastructure of a large urban health system and to discuss the outcomes of this service. SETTING: Minnesota from September 2012 to December 2013. The health system has more than 50 primary care and specialty clinics. Eighteen credentialed MTM pharmacists are located in 16 different primary care and specialty settings, with the greatest number of pharmacists providing services in the internal medicine clinic. PRACTICE INNOVATION: Home-based MTM was promoted throughout the clinics within the health system. Physicians, advanced practice providers, nurses, and pharmacists could refer patients to receive MTM in their homes. A home visit had the components of a clinic-based visit and was documented in the electronic health record (EHR); however, providing the service in the home allowed for a more direct assessment of environmental factors affecting medication use. EVALUATION: Number of home MTM referrals, reason for referral and type of referring provider, number and type of medication-related problems (MRPs). RESULTS: In the first 15 months, 74 home visits were provided to 53 patients. Sixty-six percent of the patients were referred from the Internal Medicine Clinic. Referrals were also received from the senior care, coordinated care, and psychiatry clinics. Approximately 50% of referrals were made by physicians. More referrals (23%) were made by pharmacists compared with advanced practice providers, who made 21% of referrals. The top 3 reasons for referral were: nonadherence, transportation barriers, and the need for medication reconciliation with a home care nurse. Patients had a median of 3 MRPs with the most common (40%) MRP related to compliance. CONCLUSION: Home-based MTM is feasibly delivered within the ambulatory care infrastructure of a health system with sufficient provider engagement as demonstrated by referrals to the service. PMID- 27000170 TI - Interprofessional care for patients with osteoporosis in a continuing care retirement community. AB - OBJECTIVES: To assess the quality of care provided to patients with osteoporosis in a continuing care retirement community (CCRC) after implementation of an interprofessional osteoporosis clinic (OPC). Specifically, quality measures were evaluated, including dual-emission X-ray absorptiometry (DXA) screening, calcium and vitamin D supplementation, and prescription treatment of osteoporosis and low bone mass in an ambulatory independent living community. SETTING: Large family medicine teaching practice that provides primary care for residents in one main practice, 5 rural satellite practices, and 2 CCRCs. An interprofessional OPC was developed at the main practice in 2005. Patients at all of the organization's sites could be referred to the main practice for osteoporosis management. A needs assessment conducted at one of the CCRCs in 2011 revealed that rates of screening and treatment were suboptimal for its residents despite availability of an off site OPC. PRACTICE INNOVATION: In 2012, a new interprofessional OPC including a physician, medical assistant, and pharmacist was replicated on-site at the CCRC so that residents had access to this service within their medical home. EVALUATION: Quality measures were evaluated after implementation of the team based OPC on-site at a CCRC and included: 1) DXA screening; 2) calcium and vitamin D supplementation; and 3) prescription treatment of osteoporosis and low bone mass. RESULTS: Twenty-nine patients were seen in the new OPC from January 2012 to August 2013. Ninety-three percent had appropriate DXA testing after OPC implementation. Patients accepted pharmacist recommendations regarding calcium and vitamin D supplementation 90% and 86% of the time, respectively. All but 4 patients received appropriate treatment for osteoporosis or low bone mass. CONCLUSION: Providing a team-based OPC on site in a CCRC improved quality measures for screening and treatment of osteoporosis and low bone mass. PMID- 27000171 TI - Food and Drug Administration: Helping pharmacists ensure that patients receive high-quality medicines. AB - OBJECTIVES: Ensuring that the drugs patients take are safe and effective is critical to the Food and Drug Administration (FDA) mission and a major reason for testing an active pharmaceutical ingredient or currently marketed drug product. To address gaps in the assessment of drug quality, FDA's Center for Drug Evaluation and Research (CDER) has created the Office of Pharmaceutical Quality (OPQ). SUMMARY: This newly formed "super-office" within CDER launched a concerted new strategy that enhances the surveillance of drug manufacturing and will bring a comprehensive approach to quality oversight. CONCLUSION: With OPQ and these new performance measures in place, FDA can sharpen its focus on issues critical to quality and can identify and respond to manufacturing issues before they become major systemic problems. PMID- 27000172 TI - Suicidal ideation and behavior as adverse events of prescribed medications: An update for pharmacists. AB - OBJECTIVES: Suicide is the tenth leading cause of death in the US, and the Food and Drug Administration (FDA) has labeled more than 125 prescription drugs for potential adverse effects of suicidal ideation and behavior. Several are in the top 200 for highest dispensed volume, including the entire class of antiepileptics. Also included are drugs used to treat urinary incontinence, an antibiotic, and smoking cessation agents. We describe the importance of pharmacists' identification and management of these complex adverse events and conclude with the potential for Department of Veterans Affairs and other big data longitudinal clinical research projects to provide additional insight into the complex causes of this adverse event. SUMMARY: Questions persist about causality (pharmacologic provocation of suicide) in the context of psychiatric treatment response (treatment emergence) and the multifactorial pathogenesis of suicidal behavior, which is distinct from suicidal ideation. In the future, big data with the use of medical records (rather than claims) may provide valuable insights into this question. CONCLUSION: Pharmacists are encouraged to file adverse event reports for suicide and suicide attempts resulting in death, disability, or hospitalization via MedWatch even if the reports are incomplete. Resources to support pharmacists managing patients at risk include hotlines, chatlines, texting, and free federally funded online training. PMID- 27000173 TI - Addressing vaccine hesitancy in the pharmacy. PMID- 27000174 TI - Brexpiprazole, cariprazine hydrochloride, and flibanserin. PMID- 27000175 TI - Community pharmacists as diabetic complication preventers? PMID- 27000176 TI - Unpacking Accountable Care: Using Organization Theory to Understand the Adoption, Implementation, Spread, and Performance of Accountable Care Organizations. PMID- 27000177 TI - Limits of Executive Control: Sequential Effects in Predictable Environments. AB - Cognitive-control theories attribute action control to executive processes that modulate behavior on the basis of expectancy or task rules. In the current study, we examined corticospinal excitability and behavioral performance in a go/no-go task. Go and no-go trials were presented in runs of five, and go and no-go runs alternated predictably. At the beginning of each trial, subjects indicated whether they expected a go trial or a no-go trial. Analyses revealed that subjects immediately adjusted their expectancy ratings when a new run started. However, motor excitability was primarily associated with the properties of the previous trial, rather than the predicted properties of the current trial. We also observed a large latency cost at the beginning of a go run (i.e., reaction times were longer for the first trial in a go run than for the second trial). These findings indicate that actions in predictable environments are substantially influenced by previous events, even if this influence conflicts with conscious expectancies about upcoming events. PMID- 27000178 TI - The Pandora Effect: The Power and Peril of Curiosity. AB - Curiosity-the desire for information-underlies many human activities, from reading celebrity gossip to developing nuclear science. Curiosity is well recognized as a human blessing. Is it also a human curse? Tales about such things as Pandora's box suggest that it is, but scientific evidence is lacking. In four controlled experiments, we demonstrated that curiosity could lead humans to expose themselves to aversive stimuli (even electric shocks) for no apparent benefits. The research suggests that humans possess an inherent desire, independent of consequentialist considerations, to resolve uncertainty; when facing something uncertain and feeling curious, they will act to resolve the uncertainty even if they expect negative consequences. This research reveals the potential perverse side of curiosity, and is particularly relevant to the current epoch, the epoch of information, and to the scientific community, a community with high curiosity. PMID- 27000179 TI - Stem cell therapy for white matter disorders: don't forget the microenvironment! AB - White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in rodent disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial. PMID- 27000182 TI - [Connective tissue diseases in adolescents]. AB - In this article we provide a brief review of systemic lupus erythematosus, juvenile dermatomyositis, systemic scleroderma, and mixed connective tissue disease in adolescents. As skin manifestations often belong to the presenting symptoms and may have a significant impact on the quality of life, dermatologists play an important role in the management of patients with connective tissue diseases. Early diagnosis and therapy onset are crucial for the patients' long term outcome. PMID- 27000180 TI - Total body irradiation with volumetric modulated arc therapy: Dosimetric data and first clinical experience. AB - BACKGROUND: To implement total body irradiation (TBI) using volumetric modulated arc therapy (VMAT). We applied the Varian RapidArcTM software to calculate and optimize the dose distribution. Emphasis was placed on applying a homogenous dose to the PTV and on reducing the dose to the lungs. METHODS: From July 2013 to July 2014 seven patients with leukaemia were planned and treated with a VMAT-based TBI technique with photon energy of 6 MV. The overall planning target volume (PTV), comprising the whole body, had to be split into 8 segments with a subsequent multi-isocentric planning. In a first step a dose optimization of each single segment was performed. In a second step all these elements were calculated in one overall dose-plan, considering particular constraints and weighting factors, to achieve the final total body dose distribution. The quality assurance comprised the verification of the irradiation plans via ArcCheckTM (Sun Nuclear), followed by in vivo dosimetry via dosimeters (MOSFETs) on the patient. RESULTS: The time requirements for treatment planning were high: contouring took 5-6 h, optimization and dose calculation 25-30 h and quality assurance 6-8 h. The couch time per fraction was 2 h on day one, decreasing to around 1.5 h for the following fractions, including patient information, time for arc positioning, patient positioning verification, mounting of the MOSFETs and irradiation. The mean lung dose was decreased to at least 80 % of the planned total body dose and in the central parts to 50 %. In two cases we additionally pursued a dose reduction of 30 to 50 % in a pre-irradiated brain and in renal insufficiency. All high dose areas were outside the lungs and other OARs. The planned dose was in line with the measured dose via MOSFETs: in the axilla the mean difference between calculated and measured dose was 3.6 % (range 1.1-6.8 %), and for the wrist/hip-inguinal region it was 4.3 % (range 1.1-8.1 %). CONCLUSION: TBI with VMAT provides the benefit of satisfactory dose distribution within the PTV, while selectively reducing the dose to the lungs and, if necessary, in other organs. Planning time, however, is extensive. PMID- 27000183 TI - Unique Outcomes in the Narratives of Young Adults Who Experienced Dating Violence as Adolescents. AB - BACKGROUND: Narrative therapy, an approach based on the reauthoring of life narratives, may be a useful psychotherapeutic strategy for youth who have experienced dating violence. OBJECTIVE: A cornerstone of narrative therapy is the concept of unique outcomes, which are moments that stand in contrast to a client's otherwise problem-saturated narratives. The purpose of this study was to identify and categorize unique outcomes embedded in narratives about adolescent dating violence. DESIGN: Text units representing unique outcomes were extracted from transcripts of interviews with 88 young adults who had experienced dating violence and were categorized using standard content analytic techniques. RESULTS: Six categories of unique outcome stories were identified: facing-facts stories, standing-up-for-myself stories, cutting-it-off stories, cutting-'em loose stories, getting-back-on-track stories, and changing-it-up stories. CONCLUSION: This typology of unique outcomes can inform clinicians who work with clients who have a history of adolescent dating violence. PMID- 27000184 TI - A Call to Leadership in the Face of an Epidemic. PMID- 27000185 TI - Gamification and the Psychology of Game Design in Transforming Mental Health Care. PMID- 27000186 TI - Investigating the influence of eating habits, body weight and television programme preferences on television viewing time and domestic computer usage. AB - BACKGROUND: The present study explored the influence of eating habits, body weight and television programme preference on television viewing time and domestic computer usage, after adjusting for sociodemographic characteristics and home media environment indicators. In addition, potential substitution or complementarity in screen time was investigated. METHODS: Individual level data were collected via questionnaires that were administered to a random sample of 2,946 Germans. The econometric analysis employed a seemingly unrelated bivariate ordered probit model to conjointly estimate television viewing time and time engaged in domestic computer usage. RESULTS: Television viewing and domestic computer usage represent two independent behaviours in both genders and across all age groups. Dietary habits have a significant impact on television watching with less healthy food choices associated with increasing television viewing time. Body weight is found to be positively correlated with television screen time in both men and women, and overweight individuals have a higher propensity for heavy television viewing. Similar results were obtained for age groups where an increasing body mass index (BMI) in adults over 24 years old is more likely to be positively associated with a higher duration of television watching. With respect to dietary habits of domestic computer users, participants aged over 24 years of both genders seem to adopt more healthy dietary patterns. A downward trend in the BMI of domestic computer users was observed in women and adults aged 25-60 years. On the contrary, young domestic computer users 18-24 years old have a higher body weight than non-users. Television programme preferences also affect television screen time with clear differences to be observed between genders and across different age groups. CONCLUSIONS: In order to reduce total screen time, health interventions should target different types of screen viewing audiences separately. PMID- 27000187 TI - Endothelial nitric oxide synthase: a potential therapeutic target for cerebrovascular diseases. AB - Endothelial nitric oxide (NO) is a significant signaling molecule that regulates cerebral blood flow (CBF), playing a pivotal role in the prevention and treatment of cerebrovascular diseases. However, achieving the expected therapeutic efficacy is difficult using direct administration of NO donors. Therefore, endothelial nitric oxide synthase (eNOS) becomes a potential therapeutic target for cerebrovascular diseases. This review summarizes the current evidence supporting the importance of CBF to cerebrovascular function, and the roles of NO and eNOS in CBF regulation. PMID- 27000188 TI - [Myasthenia gravis]. AB - Myasthenia gravis is an autoimmune disease, which leads to load-dependent weakness of voluntary skeletal muscles with recovery of function after resting. The disease is caused by autoantibodies directed against the postsynaptic nicotinic acetylcholine receptors (AChR) leading to a reduction of neuromuscular transmission. Muscles and nerves are not affected. Disorders of the thymus play a role in the pathogenesis of AChR antibody-positive myasthenia. The clinical symptoms include exercise-induced fatigue either of the ocular muscles alone (ocular myasthenia) or striated skeletal muscle and the ocular, facial and bulbar musculature (generalized myasthenia). Treatment of myasthenia gravis involves administration of acetylcholine esterase inhibitors and immunosuppressive drugs. A myasthenic crisis is characterized by life-threatening complications with severe weakness, swallowing difficulties and respiratory failure, which requires intensive care treatment. PMID- 27000189 TI - The enhancement of chondrogenesis of ATDC5 cells in RGD-immobilized microcavitary alginate hydrogels. AB - In our previous work, we have developed an effective microcavitary alginate hydrogel for proliferation of chondrocytes and maintenance of chondrocytic phenotype. In present work, we investigated whether microcavitary alginate hydrogel could promote the chondrogenesis of progenitor cells. Moreover, we attempted to further optimize this system by incorporating synthetic Arg-Gly-Asp peptide. ATDC5 cells were seeded into microcavitary alginate hydrogel with or without Arg-Gly-Asp immobilization. Cell Counting Kit-8 and live/dead staining were conducted to analyze cell proliferation. Real-time polymerase chain reaction (RT-PCR), hematoxylin and eosin, and Toluidine blue O staining as well as Western blot assay was performed to evaluate the cartilaginous markers at transcriptional level and at protein level, respectively. The obtained data demonstrated that Arg Gly-Asp-immobilized microcavitary alginate hydrogel was preferable to promote the cell proliferation. Also, Arg-Gly-Asp-immobilized microcavitary alginate hydrogel improved the expression of chondrocytic genes including Collagen II and Aggrecan when compared with microcavitary alginate hydrogel. The results suggested that microcavitary alginate hydrogel could promote the chondrogenesis. And Arg-Gly-Asp would be promising to ameliorate this culture system for cartilage tissue engineering. PMID- 27000191 TI - Helping Students Turn Scholarly Projects and Papers Into Publishable Articles. PMID- 27000190 TI - Reasons behind providing futile medical treatments in Iran. AB - BACKGROUND: Despite their negative consequences, evidence shows that futile medical treatments are still being provided, particularly to terminally ill patients. Uncovering the reasons behind providing such treatments in different religious and sociocultural contexts can create a better understanding of medical futility and help manage it effectively. RESEARCH OBJECTIVES: This study was undertaken to explore Iranian nurses' and physicians' perceptions of the reasons behind providing futile medical treatments. RESEARCH DESIGN: This was a qualitative exploratory study. Study data were gathered through conducting in depth semi-structured personal interviews and analyzed using the conventional content analysis method. Participants and research context: Twenty-one nurses and nine medical specialists were recruited purposively from four teaching hospitals affiliated to Tehran University of Medical Sciences. Ethical considerations: This study was approved by the Nursing and Midwifery Research Center and the Research Ethics Committee of Tehran University of Medical Sciences. All participants gave informed consent for the research and that their anonymity was preserved. FINDINGS: The main theme of the study was "having an obligation to provide medical treatments despite knowing their futility." This theme consisted of three main categories including patients' and family members' request for continuing life-sustaining treatments, healthcare professionals' personal motives, and organizational atmosphere and structure. DISCUSSION AND CONCLUSION: Different personal and organizational factors contribute to providing futile medical treatments. Promoting the structure and the function of hospital ethics committees, establishing and developing home care facilities, increasing the number of palliative care centers and hospices, and educating healthcare professionals, patients, and family members about the services and the benefits of such centers can facilitate making wise decisions about continuing or discontinuing treatments which have been labeled as futile. PMID- 27000192 TI - Nurses Returning to School: Motivators, Inhibitors and Job Satisfaction. AB - Health care employers and national nursing organizations are placing increased emphasis on nurses earning a baccalaureate degree or higher. This study examines the impact of motivators (professional and personal motivation), inhibitors (time constraints and employer discouragement), and job satisfaction on intent to return to school. Approximately half of the employed nurses in Wyoming were surveyed using a mailed questionnaire in the summer of 2013. Perceived employer discouragement and time constraints continued to play a direct role on intent to return to school regardless of nurse motivation or job satisfaction. However, motivation and job satisfaction also contributed to a nurse's intent to return to school. These results suggest that motivation and job satisfaction are significant regarding intent to return to school but can be limited by both perceived discouragement of one's employer and perceived time constraints. In order to meet the increasing demands of a better-educated nursing workforce, a shift in workplace dynamics may be warranted. PMID- 27000193 TI - Innovation in Faculty Practice: A College of Nursing and Juvenile Justice Collaboration. AB - Residential Juvenile Justice Services (JJS) facilities are located in every state and, in general, represent an underserved and diverse adolescent population. The JJS centers present an exciting and innovative opportunity for collaboration with colleges of nursing to initiate faculty practice sites. The University of Utah College of Nursing has been serving 5 JJS centers for 14 years and recently doubled its services to incorporate 10 different JJS Centers in the state of Utah. Each center offers a unique patient population and setting providing the student with an opportunity to learn health assessment and physical examination skills not typically presented in more traditional hospital or outpatient facilities. This type of community collaboration affords an opportunity for faculty practice, education, research, and service. An interprofessional focus enriches the experience. PMID- 27000194 TI - Service Learning in Undergraduate Nursing Education: Strategies to Facilitate Meaningful Reflection. AB - Service learning is recognized as a valuable pedagogy involving experiential learning, reflection, and reciprocal learning. Students develop critical thinking and social awareness by using the crucial activity of reflecting upon their experiential learning with community partners. The purpose of this paper is to demystify the process of reflection by identifying best practices to enhance reflection and offering suggestions for grading. By understanding "the what" and "the how" of reflection, educators can implement service learning experiences designed to include the essential component of reflection. Strategies for facilitating meaningful reflection are described including descriptions of what students should reflect upon and how to initiate reflection through writing, reading, doing, and telling. Grading rubrics are suggested to facilitate evaluation of student reflection. When properly implemented, service learning encourages students to be good citizens of the world. By using best practices associated with reflection, students can be challenged to think critically about the world and how their service can achieve community goals. PMID- 27000195 TI - The Lived Experience of Minority Nursing Faculty: A Phenomenological Study. AB - The lived experience of full-time nursing faculty has recently been detailed. However, similar information is not available about minority nursing faculty. PURPOSE: The purpose is to explore the lived experience of minority nursing faculty. DESIGN: The design is a phenomenological study. METHODS: Five female faculty with 8 to 13 years of experience in a full-time position shared experiences through face-to-face interviews. A simplified version of Hycner's five-step explicitation process was used for interpretation and data analysis. FINDINGS: Six themes emerged--missing mentorship, lack of collegial support, harnessing external support, acculturation, feeling isolated, and I feel more like a minority here. DISCUSSION: Minority nursing faculty face challenges similar to minority faculty in other disciplines in higher institutions. However, acculturation has not been discussed in phenomenological studies of similar populations. CONCLUSION: These findings have bearings on strategies for increasing minority nursing faculty and assessing mentoring practices in nursing programs. PMID- 27000196 TI - Design and Implementation of an International Nurse Faculty Partnership. AB - Haiti has the highest rates of infant, under 5 years old, and maternal mortality in the Americas. More nurses are needed throughout the country, but there is a deficit of nursing faculty. Increasing numbers and quality of nursing faculty members will ensure a sustainable, positive impact on the country's nursing profession. The International Nurse Faculty Partnership Initiative was designed to educate a total of 36 current Haitian nurse faculty members at the master's degree level. The first cohort of 12 nurse faculty members completed the program of study in February 2014, graduating with a master's degree in nursing from the State University of Haiti. Performance evaluation by their respective deans revealed that the Haitian nursing faculty members demonstrated increases in teaching effectiveness and critical thinking in comparison to their premaster's degree skill levels. The International Nurse Faculty Partnership Initiative expects to graduate a total of 36 master's-level-prepared nurse educators. Currently, program graduates and nursing leaders from Haiti's Ministry of Health are working with the State University of Haiti to establish the faculty of nursing within the institution, creating a system for the ongoing delivery of baccalaureate-level and master-level nursing education within that country. PMID- 27000197 TI - Coaching Model + Clinical Playbook = Transformative Learning. AB - Health care employers demand that workers be skilled in clinical reasoning, able to work within complex interprofessional teams to provide safe, quality patient centered care in a complex evolving system. To this end, there have been calls for radical transformation of nursing education including the development of a baccalaureate generalist nurse. Based on recommendations from the American Association of Colleges of Nursing, faculty concluded that clinical education must change moving beyond direct patient care by applying the concepts associated with designer, manager, and coordinator of care and being a member of a profession. To accomplish this, the faculty utilized a system of focused learning assignments (FLAs) that present transformative learning opportunities that expose students to "disorienting dilemmas," alternative perspectives, and repeated opportunities to reflect and challenge their own beliefs. The FLAs collected in a "Playbook" were scaffolded to build the student's competencies over the course of the clinical experience. The FLAs were centered on the 6 Quality and Safety Education for Nurses competencies, with 2 additional concepts of professionalism and systems-based practice. The FLAs were competency-based exercises that students performed when not assigned to direct patient care or had free clinical time. Each FLA had a lesson plan that allowed the student and faculty member to see the competency addressed by the lesson, resources, time on task, student instructions, guide for reflection, grading rubric, and recommendations for clinical instructor. The major advantages of the model included (a) consistent implementation of structured learning experiences by a diverse teaching staff using a coaching model of instruction; (b) more systematic approach to present learning activities that build upon each other; (c) increased time for faculty to interact with students providing direct patient care; (d) guaranteed capture of selected transformative learning experiences; (e) increased student reflection to promote transformative learning; and (f) provided avenues for timely feedback to students. PMID- 27000198 TI - Using Simulation to Teach About Poverty in Nursing Education: A Review of Available Tools. AB - Poverty is one of the most significant social determinants of health, and as such, it is imperative that nurses have an understanding of the impact that living in poverty has upon one's life and health. A lack of such understanding will impede nurses from providing care that is patient centered, treats all patients fairly, and advocates for social justice. It is essential that nursing educators assure that poverty-related content and effective teaching strategies are used in nursing curricula in order to help students develop this understanding. Several poverty-simulation tools are available and may be able to assist with development of accurate knowledge, skills, and attitudes. Unfortunately, little evidence exists to evaluate most poverty simulation tools. This article will provide an introduction to several poverty-related simulation tools, discuss any related research that evaluates their effectiveness, and make recommendations for integration of such simulation tools into nursing curricula. PMID- 27000199 TI - Altering Nursing Student and Older Adult Attitudes Through a Possible Selves Ethnodrama. AB - The purpose of this mixed method study is to evaluate the effects of participation in the development and implementation of ethnodrama about possible selves on nursing student attitudes toward older adults and older adult attitudes to aging. Twelve nursing students and 12 older adult long-term care residents collaborated in a transformational learning experience involving interviews on the topic of possible selves culminating in the presentation of an ethnodrama developed from these data. Longitudinal data from student surveys about attitudes toward older adults were analyzed using growth modeling, whereas older adult pre post data on attitudes toward aging were analyzed with a paired samples t test. Video of group discussions and open-ended feedback on the overall experience were analyzed to provide qualitative understanding of change in student attitudes over time. Although positive overall, student attitudes varied in initial status and rate of change. Students who interacted most frequently with older adults had more neutral attitudes. Older adult attitudes surrounding psychosocial loss improved over the course of the intervention. Normalizing attitudes may be as important as improving attitudes; neutrality may be more representative of realistic perceptions of older adults and late-life potential. PMID- 27000200 TI - Residency Programs and Clinical Leadership Skills Among New Saudi Graduate Nurses. AB - Nurse residency programs have been adopted by health care organizations to assist new graduate nurses with daily challenges such as intense working environments, increasing patient acuity, and complex technologies. Overall, nurse residency programs are proven beneficial in helping nurses transition from the student role to independent practitioners and bedside leaders. The purpose of this study was to assess the impact of residency programs on leadership skills of new Saudi graduate nurses who completed a residency program compared to new Saudi graduate nurses who did not participate in residency programs. The study design was cross sectional involving a convenience sample (n = 98) of new graduate nurses from three hospitals in Saudi Arabia. The Clinical Leadership Survey was used to measure the new graduate nurses' clinical leadership skills based on whether they completed a residency program or not. Descriptive statistics, correlation, and multiple linear regression analyses were conducted to examine leadership skills in this sample of new Saudi graduate nurses. A significant difference was found between residents and nonresidents in their leadership skills (t = 10.48, P = .000). Specifically, residents were significantly more likely to show higher levels of leadership skills compared to their counterparts. Attending a residency program was associated with a significant increase in clinical leadership skills. The findings of this study indicate that there is a need to implement more residency programs in hospitals of Saudi Arabia. It is imperative that nurse managers and policy makers in Saudi Arabia consider these findings to improve nurses' leadership skills, which will in turn improve patient care. Further research should examine how residency programs influence new graduate nurses' transition from student to practitioner with regard to clinical leadership skills in Saudi Arabia. PMID- 27000201 TI - Erratum to: RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial-mesenchymal transition. AB - Erratum to: Breast Cancer Res Treat (2013),142:297-309,DOI 10.1007/s10549-013 2737-1.In the original publication, the images in Fig. 3 were mistakenly selected from other experiments in which similar procedures were performed. The corrected Fig. 3 is given in this erratum. PMID- 27000203 TI - An acid-base disorders analysis with the use of the Stewart approach in patients with sepsis treated in an intensive care unit. AB - BACKGROUND: Patients with sepsis admitted to the intensive care unit often present with acid-base disorders. As the traditional interpretation might be clinically misleading, an alternative approach described by Stewart may allow one to quantify the individual components of acid-base abnormalities and provide an insight into their pathogenesis. The aim of our study was to compare the traditional and Stewart approaches in the analysis of acid-base disturbance. METHODS: We analyzed arterial blood gases (ABG) taken from 43 ICU septic patients from admission to discharge categorising them according to SBE values. The traditional concept analysis was compared with the physicochemical approach using the Stewart equations. RESULTS: 990 ABGs were analysed. In the SBE < -2 mEq L-1 group, hyperlactatemia was observed in 34.7% ABG, hypoalbuminemia in 100% and SIG acidosis in 42% ABG. Moreover, a Cl/Na ratio > 0.75 was present in 96.9% ABG. In the normal range SBE group, elevated lactates were present in 21.3% ABG, SIG acidosis in 14.9%, elevated Cl/Na ratio in 98.4% and hypoalbuminemia in all 324 ABG. In the metabolic alkalosis group (SBE > +2 mEq L-1), hyperlactatemia was observed in 18.4% ABG, SIG acidosis in 5% ABG, Cl/Na ratio> 0.75 in 88.8%, while 99.1% samples revealed hypoalbuminemia. CONCLUSION: The use of the Stewart model may improve our understanding of the underlying pathophysiological mechanism and the true etiology of the derangements of acid-base disorders. Indeed, it proves that patients may suffer from mixed arterial blood gas disorders hidden under normal values of SBE and pH. PMID- 27000202 TI - Valosin-containing protein is a key mediator between autophagic cell death and apoptosis in adult hippocampal neural stem cells following insulin withdrawal. AB - BACKGROUND: Programmed cell death (PCD) plays essential roles in the regulation of survival and function of neural stem cells (NSCs). Abnormal regulation of this process is associated with developmental and degenerative neuronal disorders. However, the mechanisms underlying the PCD of NSCs remain largely unknown. Understanding the mechanisms of PCD in NSCs is crucial for exploring therapeutic strategies for the treatment of neurodegenerative diseases. RESULT: We have previously reported that adult rat hippocampal neural stem (HCN) cells undergo autophagic cell death (ACD) following insulin withdrawal without apoptotic signs despite their normal apoptotic capabilities. It is unknown how interconnection between ACD and apoptosis is mediated in HCN cells. Valosin-containing protein (VCP) is known to be essential for autophagosome maturation in mammalian cells. VCP is abundantly expressed in HCN cells compared to hippocampal tissue and neurons. Pharmacological and genetic inhibition of VCP at basal state in the presence of insulin modestly impaired autophagic flux, consistent with its known role in autophagosome maturation. Of note, VCP inaction in insulin-deprived HCN cells significantly decreased ACD and down-regulated autophagy initiation signals with robust induction of apoptosis. Overall autophagy level was also substantially reduced, suggesting the novel roles of VCP at initial step of autophagy. CONCLUSION: Taken together, these data demonstrate that VCP may play an essential role in the initiation of autophagy and mediation of crosstalk between ACD and apoptosis in HCN cells when autophagy level is high upon insulin withdrawal. This is the first report on the role of VCP in regulation of NSC cell death. Elucidating the mechanism by which VCP regulates the crosstalk of ACD and apoptosis will contribute to understanding the molecular mechanism of PCD in NSCs. PMID- 27000205 TI - Innovations in healthcare and medicine editorial. AB - This special issue editorial begins with a brief discussion on the current trends of innovations in healthcare and medicine driven by the evolution of sensing devices as well as the information processing techniques, and the social media revolution. This discussion aims to set the stage for the actual papers accepted for the special issue which are extensions of the papers presented at the InMed 2014 conference held in San Sebastian, Spain, in July 2014. PMID- 27000204 TI - [Fracture arthroplasty of femoral neck fractures]. AB - A paradigm shift in the treatment of elderly patients has recently taken place leading to an increase in joint replacement surgery. The aim of this article is to highlight new developments and to present a treatment algorithm for femoral neck fractures. The age limit must be individually determined considering the comorbidities and perioperative risk profile. Pertrochanteric femoral fractures are nearly exclusively treated by osteosynthesis regardless of age. The situation for femoral neck fractures is more complex. Patients younger than 65 years should generally be treated by osteosynthesis but patients older than 65 years benefit from hemiarthroplasty or total hip arthroplasty. In patients aged between 65 and 75 years with high functional demands and a justifiable perioperative risk, total joint replacement is the treatment of choice. In physically less active patients older than 75 years and poor general condition, preference should be given to hemiarthroplasty. PMID- 27000206 TI - Mortality risk from comorbidities independent of triple-negative breast cancer status: NCI-SEER-based cohort analysis. AB - PURPOSE: A comparatively high prevalence of comorbidities among African American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients. METHODS: We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. RESULTS: Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74 3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of >=3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90 11.02). A lower and nonsignificant effect was observed for whites with a CCI of >=3 (Adj. HR 1.90, 95 % CI 0.68-5.29). CONCLUSIONS: comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk. PMID- 27000207 TI - Feedback modulation of neural network synchrony and seizure susceptibility by Mdm2-p53-Nedd4-2 signaling. AB - BACKGROUND: Neural network synchrony is a critical factor in regulating information transmission through the nervous system. Improperly regulated neural network synchrony is implicated in pathophysiological conditions such as epilepsy. Despite the awareness of its importance, the molecular signaling underlying the regulation of neural network synchrony, especially after stimulation, remains largely unknown. RESULTS: In this study, we show that elevation of neuronal activity by the GABA(A) receptor antagonist, Picrotoxin, increases neural network synchrony in primary mouse cortical neuron cultures. The elevation of neuronal activity triggers Mdm2-dependent degradation of the tumor suppressor p53. We show here that blocking the degradation of p53 further enhances Picrotoxin-induced neural network synchrony, while promoting the inhibition of p53 with a p53 inhibitor reduces Picrotoxin-induced neural network synchrony. These data suggest that Mdm2-p53 signaling mediates a feedback mechanism to fine-tune neural network synchrony after activity stimulation. Furthermore, genetically reducing the expression of a direct target gene of p53, Nedd4-2, elevates neural network synchrony basally and occludes the effect of Picrotoxin. Finally, using a kainic acid-induced seizure model in mice, we show that alterations of Mdm2-p53-Nedd4-2 signaling affect seizure susceptibility. CONCLUSION: Together, our findings elucidate a critical role of Mdm2-p53-Nedd4-2 signaling underlying the regulation of neural network synchrony and seizure susceptibility and reveal potential therapeutic targets for hyperexcitability associated neurological disorders. PMID- 27000208 TI - Headache as the leading symptom in a case of cerebral tuberculosis. AB - The advent of new and acute headaches poses a diagnostic challenge. The differential diagnosis comprises numerous diseases and syndromes, the prevalence of which varies depending on the geographical region. Due to increased magnitudes in international migration, the usual differential diagnostic spectrum has to be enlarged in individual cases. The presented case illustrates this dilemma and shows that, for example, tuberculosis deserves to be taken into consideration. PMID- 27000209 TI - The CO2 stimulus for cerebrovascular reactivity: Fixing inspired concentrations vs. targeting end-tidal partial pressures. AB - Cerebrovascular reactivity (CVR) studies have elucidated the physiology and pathophysiology of cerebral blood flow regulation. A non-invasive, high spatial resolution approach uses carbon dioxide (CO2) as the vasoactive stimulus and magnetic resonance techniques to estimate the cerebral blood flow response. CVR is assessed as the ratio response change to stimulus change. Precise control of the stimulus is sought to minimize CVR variability between tests, and show functional differences. Computerized methods targeting end-tidal CO2 partial pressures are precise, but expensive. Simpler, improvised methods that fix the inspired CO2 concentrations have been recommended as less expensive, and so more widely accessible. However, these methods have drawbacks that have not been previously presented by those that advocate their use, or those that employ them in their studies. As one of the developers of a computerized method, I provide my perspective on the trade-offs between these two methods. The main concern is that declaring the precision of fixed inspired concentration of CO2 is misleading: it does not, as implied, translate to precise control of the actual vasoactive stimulus - the arterial partial pressure of CO2 The inherent test-to-test, and therefore subject-to-subject variability, precludes clinical application of findings. Moreover, improvised methods imply widespread duplication of development, assembly time and costs, yet lack uniformity and quality control. A tabular comparison between approaches is provided. PMID- 27000210 TI - Intraoperative mild hypothermia for postoperative neurological deficits in people with intracranial aneurysm. AB - BACKGROUND: Rupture of an intracranial aneurysm causes aneurysmal subarachnoid haemorrhage, which is one of the most devastating clinical conditions. It can be classified into five Grades using the Hunt-Hess or World Federation of Neurological Surgeons (WFNS) scale. Grades 4 and 5 predict poor prognosis and are known as 'poor grade', while grade 1, 2, and 3 are known as 'good grade'. Disturbances of intracranial homeostasis and brain metabolism are known to play certain roles in the sequelae. Hypothermia has a long history of being used to reduce metabolic rate, thereby protecting organs where metabolism is disturbed, and may potentially cause harm. OBJECTIVES: To assess the effect of intraoperative mild hypothermia on postoperative death and neurological deficits in people with ruptured or unruptured intracranial aneurysms. SEARCH METHODS: We updated the search in the Cochrane Stroke Group Trials Register (August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 8), WHO International Clinical Trials Registry Platform (ICTRP; December 2015), MEDLINE (1950 to September 2015), EMBASE (1980 to September 2015), Science Citation Index (1900 to September 2015), and 11 Chinese databases (September 2015). We also searched ongoing trials registers (September 2015) and scanned reference lists of retrieved records. SELECTION CRITERIA: We included only randomised controlled trials that compared intraoperative mild hypothermia (32 degrees C to 35 degrees C) with control (no hypothermia) in people with ruptured or unruptured intracranial aneurysms. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and assessed the risk of bias for each included study. We presented data as risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI). MAIN RESULTS: We included three studies, enrolling 1158 participants. Each study reported an increased rate of recovery with intraoperative mild hypothermia, but the effect sizes were not sufficient for certainty. A total of 1086 of the 1158 participants (93.8%) had good grade aneurysmal subarachnoid haemorrhage. Seventy-six of 577 participants (13.1%) who received hypothermia and 93 of 581 participants (16.0%) who did not receive hypothermia were dead or dependent (RR 0.82; 95% CI 0.62 to 1.09; RD -0.03; 95% CI -0.07 to 0.01, moderate-quality evidence) after three months.Reported unfavourable outcomes did not differ between participants with or without hypothermia. The quality of evidence for these outcomes remains unclear because the outcomes were reported in a variety of ways. No decompressive craniectomy or corticectomy was reported. Thirty-six of 577 (6.2%) participants with hypothermia and 40 of 581 (6.9%) participants without hypothermia had infarction. Thirty-four of 577 (6%) participants with hypothermia and 32 of the 581 (5.5%) participants without hypothermia had clinical vasospasm (temporary deficits).Duration of hospital stay was not reported. Only one study with 112 participants reported discharge destinations: 43 of 55 (78.2%) participants with hypothermia and 39 of 57 (68.4%) participants in the control group were discharged home. The remaining participants were discharged to other facilities.Thirty-nine of 577 (6.8%) participants with hypothermia and 39 of 581 (6.7%) participants without hypothermia had infections. Six of 577 (1%) participants with hypothermia and 6 of 581 (1%) participants without hypothermia had cardiac arrhythmia. AUTHORS' CONCLUSIONS: It remains possible that intraoperative mild hypothermia could prevent death or dependency in activities of daily living in people with good grade aneurysmal subarachnoid haemorrhage. However, the confidence intervals around this estimate include the possibility of both benefit and harm. There was insufficient information to draw any conclusions about the effects of intraoperative mild hypothermia in people with poor grade aneurysmal subarachnoid haemorrhage or without subarachnoid haemorrhage. We did not identify any reliable evidence to support the routine use of intraoperative mild hypothermia. A high quality randomised clinical trial of intraoperative mild hypothermia for postoperative neurological deficits in people with poor grade aneurysmal subarachnoid haemorrhage might be feasible. PMID- 27000211 TI - The impacts of premorbid hypertension treatment on functional outcomes of ischemic stroke. AB - BACKGROUND AND PURPOSE: The low rate of hypertension control is a major cause for the high rate of stroke morbidity and mortality in China. This study aimed to evaluate the impacts of premorbid hypertension treatment on the functional outcomes in patients with acute ischemic stroke and hypertension. METHODS: Patients with first-ever ischemic stroke and hypertension were screened from Nanjing Stroke Registry Program for eligibility. Functional outcomes were followed at 3 months with modified Rankin Scale (mRS). A good functional outcome was defined as mRS<=2. Potential factors associated with good functional outcomes were analyzed with multivariate logistic regression. RESULTS: A total of 660 patients with both ischemic stroke and hypertension were included, of whom 284 (43.0%) were on antihypertensives before stroke. In univariate analysis, more patients with hypertension treatments had good outcomes than those without (47.7% vs 31.0%, P=0.0001). After adjusted for age, heart diseases, baseline stroke severity, systolic blood pressure at admission, pneumonia, intravenous thrombolysis, and hospital stay, multivariate logistic regression indicated that premorbid hypertension treatment was related to an increased likelihood of good functional outcomes (OR: 2.21, 95% CI: 1.30 to 3.74, P=0.003). CONCLUSIONS: Less than half of the Chinese patients with hypertension were on drug treatment prior to stroke onset. Lack of premorbid hypertension treatment may have deteriorated functional outcomes of stroke. These findings emphasized the importance of improving hypertension treatment in Chinese, especially in whom at high risk of cerebrovascular diseases. PMID- 27000212 TI - Neurotrophic factors in Parkinson's disease are regulated by exercise: Evidence based practice. AB - We carried out a qualitative review of the literature on the influence of forced or voluntary exercise in Parkinson's Disease (PD)-induced animals, to better understand neural mechanisms and the role of neurotrophic factors (NFs) involved in the improvement of motor behavior. A few studies indicated that forced or voluntary exercise may promote neuroprotection, through upregulation of NF expression, against toxicity of drugs that simulate PD. Forced training, such as treadmill exercise and forced-limb use, adopted in most studies, in addition to voluntary exercise on a running wheel are suitable methods for NFs upregulation. PMID- 27000213 TI - The association between rural residence and stroke care and outcomes. AB - BACKGROUND: Little is known about stroke care and outcomes in those residing in rural compared to urban areas. METHODS: We conducted a cohort study on a population-based sample of patients with stroke or transient ischemic attack seen at 153 acute care hospitals in the province of Ontario, Canada, between April 1, 2008 and March 31, 2011. Based on their primary residence, patients were categorized as residing in a rural (population<10,000), medium urban (population 10,000-99,999) or large urban (population>=100,000) area. In the study sample of 15,713, we compared processes of stroke care (use of thrombolysis, stroke unit care, investigations, consultations and treatments) and outcomes (30-day mortality, disability at discharge) in those from rural and urban areas, with multivariable models constructed to evaluate the association between rural residence and outcomes after adjustment for potential confounders. RESULTS: Patients from rural areas were less likely than those from urban areas to receive stroke unit care, brain imaging within 24 h, carotid imaging, and consultations from neurologists, physiotherapists, occupational therapists and speech language pathologists, and were less likely to be transferred to inpatient rehabilitation facilities. Use of antithrombotic agents and lipid lowering therapy was similar in rural and urban residents, as was disability at discharge. There was a trend toward higher 30-day mortality in rural compared to urban residents (adjusted hazard ratio 1.14; 95% confidence interval 0.99-1.32). CONCLUSION: Rural residence is associated with lower use of key stroke care interventions after stroke. Future work should focus on developing interventions to address gaps in stroke care in rural areas. PMID- 27000214 TI - Long-term observation of neuronal degeneration and microgliosis in the gerbil dentate gyrus after transient cerebral ischemia. AB - Ischemic insults in the central nervous system evoke activation of microglia. In this study, we investigated long-term changes of neuronal damage and microglial activation in the gerbil dentate gyrus for 60 days after transient cerebral ischemia using immunohistochemistry and western blot. Neuronal damage or death was hardly found in the dentate gyrus after transient ischemia using cresyl violet staining and NeuN immunohistochemistry; however, neuronal degeneration was detected in the polymorphic layer of the dentate gyrus using Fluoro-Jade (F-J) B staining. F-J B-positive cells were significantly increased after ischemia reperfusion (I-R) and peaked at 3 days post-ischemia, thereafter, F-J B-positive cells were decreased in a time-dependent manner and shown until 30 days post ischemia; no F-J B-positive cells were observed 60 days after I-R. On the other hand, Iba-1-immunoreactive microglia were hypertrophied after I-R, and numbers of Iba-1-immunoreactive microglia were significantly increased along with the neuronal degeneration and highest 7 days after I-R, thereafter, numbers of Iba-1 immunoreactive microglia were decreased with time, although microglia activation lasted up to 60 days after I-R. In addition, Iba-1 protein level in the dentate gyrus after I-R was changed like immunohistochemical change. Our results, in brief, indicate that transient ischemia-induced neuronal degeneration in the dentate gyrus is maintained for about 30 days after I-R and that microglial activation lasts up to, at least, 60 days after I-R in the gerbil dentate gyrus after transient cerebral ischemia. PMID- 27000215 TI - The abduction deficit of functional convergence spasm. PMID- 27000216 TI - Renin-angiotensin system gene polymorphisms as risk factors for multiple sclerosis. AB - The components of renin-angiotensin system, such as angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II receptor type 1 and 2 (AT1R and AT2R), are expressed in the central nervous system and leukocytes and proposed to be involved in the inflammation and pathogenesis of multiple sclerosis (MS). ACE I/D, AT1R 1166A/C and AT2R -1332A/G are functional polymorphisms associated with phenotypes of diverse chronic inflammatory diseases. The aim of this study was to investigate the association between ACE I/D, AT1R 1166A/C and AT2R -1332A/G gene polymorphisms and MS in Serbian population. A total of 470 MS patients and 478 controls participated in the study. Allele-specific polymerase chain reaction (PCR) was performed for genotyping of the ACE polymorphism. The AT1R and AT2R genotyping was done by duplex PCR and restriction fragment length polymorphism analysis. Both ACE homozygotes, II and DD, were significantly overrepresented in MS patients, compared to controls (chi(2) test p=0.03). Neither genotype nor allele frequencies of AT1R 1166A/C polymorphism were significantly different between patients and controls. Significant overrepresentation of AT2R -1332 AA genotype in female patients, compared to female controls, was detected (OR=1.67, 95%CI=1.13-2.49, chi(2) test p=0.01), suggesting that this genotype could be a gender-specific genetic risk factor for MS. PMID- 27000217 TI - Subcutaneous interferon beta-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study. AB - BACKGROUND: To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). METHODS: Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon beta-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [<12 years] and adolescents [12-17 years]). RESULTS: US adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5 kg/m(2)), started disease modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon beta-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon beta-1a to another DMT before the end of the observation period. CONCLUSIONS: This retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon beta-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance. PMID- 27000218 TI - CIDP in a HIV endemic population: A prospective case series from Johannesburg, South Africa. AB - OBJECTIVE: To describe patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in Johannesburg, South Africa, a setting of high HIV prevalence, and to determine the influence, if any, of HIV on CIDP. METHODS: Patients were recruited prospectively. The study design was a hospital based case series of unselected consecutive CIDP patients. CIDP was diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society criteria for the diagnosis of CIDP (First Revision). Demographic, clinical, laboratory and electrophysiological data were documented. RESULTS: Twenty three patients with CIDP were recruited over a two year period. Mean age was 38 years. The female to male ratio was 3.6:1. Less than half (43%) had a raised cerebrospinal fluid (CSF) protein. All patients had idiopathic CIDP, three had associated diabetes mellitus. Ten patients (43%) were HIV positive. Thirteen patients were HIV negative. Clinical and electrophysiological characteristics were identical in the two groups. In the HIV positive group all the patients were black females. The CD4 counts ranged from 87 to 747 cells/mm(3). HIV positive status was associated with a progressive disease course and significantly with a CSF lymphocytic pleocytosis (p=0.007). Albuminocytological dissociation was associated with HIV negative status. CONCLUSIONS: Testing for HIV in patients with CIDP in a region of high HIV prevalence is recommended. CSF lymphocytic pleocytosis occurs in HIV associated CIDP. PMID- 27000219 TI - Neuroprotective and restorative effects of the brain-derived neurotrophic factor in retinal diseases. AB - Brain-derived neurotrophic factor (BDNF) is a neurotrophin proposed to be implicated in ameliorating the course of some neurodegenerative disorders. Given the fact that retina is considered as an out-pouching of the central nervous system, its related diseases have long been suggested to receive protective influence from this signaling molecule. The role of BDNF in retinal neurorestoration, neuroprotection and oxidative stress has extensively been tested over the past two decades. Nonetheless, almost the entire related literature root in animal studies and clinical research on this topic is lacking. Although much of the evidence have validated the protective properties of BDNF against various retinal cell diseases, bringing such insights into clinical context would depend on further well-designed research. The present review is an attempt to categorize and discuss the available evidence with regard to the BDNF and retinal diseases. PMID- 27000220 TI - Factors associated with favorable outcome in botulinum toxin A treatment for chronic migraine: A clinic-based prospective study. AB - BACKGROUND: Botulinum toxin A (BTA) responders have elevated levels of calcitonin gene-related and vasoactive intestinal peptides, which are potent vasodilators. We aimed to investigate neurovascular features as a predictor of BTA treatment response in patients with chronic migraine. METHODS: We prospectively recruited South Korean patients who were diagnosed with chronic migraine and underwent BTA injection at a university hospital from December 2013 to January 2015. Interictal transcranial Doppler (TCD) test was performed before BTA treatment when patients did not experience moderate-to-severe headache attacks. Botulinum toxin A was injected per the Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol. Treatment response was determined after 4-6 weeks of follow up. Pretreatment clinical and neurosonologic features of responders and non responders were analyzed. RESULTS: Of the 83 enrolled patients, 70 who completed initial and follow-up evaluations were included for this study. Forty-two (60.0%) patients were classified as responders. 50% responders were 31 (44.2%). Longer disease duration was associated with poor treatment outcome (p=0.019). The ratio of the mean velocity of middle cerebral artery to that of ipsilateral internal carotid artery (MCA/ICA index) was significantly higher in responders than non responders (p=0.027) and remained significant after controlling for covariates (p=0.025). CONCLUSIONS: Shorter disease duration and higher pretreatment MCA/ICA index on TCD are associated with good early outcomes of BTA treatment. PMID- 27000221 TI - Iowa APP mutation-related hereditary cerebral amyloid angiopathy (CAA): A new family from Spain. PMID- 27000222 TI - Association of NOD1 and NOD2 polymorphisms with Guillain-Barre syndrome in Northern Indian population. AB - BACKGROUND: Nucleotide oligomerization domain (NOD) proteins are cytosolic pattern recognition receptors that respond to bacterial substrate and induce NF kappaB activation in host. Association of NOD polymorphisms have been studied in many autoimmune disorders, however its role in Guillain-Barre syndrome (GBS) remains unknown. We have investigated NOD1 Glu266Lys and NOD2 (Arg702Trp and Gly908Arg) gene polymorphisms among patients with GBS. MATERIALS AND METHOD: Polymorphisms in NOD-1 (Glu266Lys) and NOD-2 (Arg702Trp and Gly908Arg) genes were studied using polymerase chain reaction-restriction fragment length polymorphism in 105 patients with GBS and 100 healthy controls. RESULTS: Homozygous genotype (Lys/Lys) of NOD1 was significantly associated with GBS (p=0.013); and its subtypes viz. acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) (p=0.008 and p=0.024 respectively) than controls. In NOD2 (Arg702Trp and Gly908Arg) polymorphisms, only heterozygous genotype (Arg/Trp and Gly/Arg) showed significant association with GBS (p=0.001 and p=0.01 respectively); subtypes AMAN, acute motor-sensory axonal neuropathy (AMSAN) and AIDP showed association with heterozygote Arg702Trp (p=0.001; p=0.029 and p=0.001 respectively) whereas only AIDP was associated with heterozygote genotype Gly908Arg (p=0.003). CONCLUSION: NOD1 (Glu266Lys) and NOD2 (Arg702Trp and Gly908Arg) polymorphisms were associated with an increased susceptibility to GBS. These polymorphisms could be genetic marker to GBS susceptibility. PMID- 27000223 TI - Blood brain barrier breakdown was found in non-infarcted area after 2-h MCAO. AB - The blood brain barrier (BBB) could be damaged within the thrombolytic time window and is considered to be a precursor to hemorrhagic transformation during reperfusion. Although we have recently reported the association between BBB damage and tissue injury within the thrombolytic time window, our knowledge about this early BBB damage is limited. In this study, rats were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 10 min reperfusion with Evan's blue as a tracer to detect BBB damage. Rat brain was sliced into 10 consecutive sections and with TTC staining, a macro and full view of the spatial distribution of BBB damage and tissue injury could be clearly seen in the same group of animals. After 2-h MCAO, tissue injury started from 2nd slice and the BBB leakage started from the 5th slice, of note, there is no colocalization between BBB damage and tissue injury. Fluoro Jade B was employed to explore the localization of neuronal degeneration, and our results showed that 2-h MCAO produced greater number of positive cells in ischemic cortex and dorsal striatum than other areas. More important, 2-h MCAO induced occludin but not claudin-5 degradation in the ischemic hemisphere and pretreatment with MMP inhibitor GM6001 significantly reduced occludin degradation as well as BBB damage detected by IgG leakage. Taken together, our findings demonstrated a "mismatch" between ischemic tissue injury and BBB leakage and a differential degradation of occludin and claudin-5 by MMP-2 after 2-h MCAO. PMID- 27000224 TI - Efficacy and safety profile of memantine in patients with cognitive impairment in multiple sclerosis: A randomized, placebo-controlled study. AB - Memantine, an uncompetitive antagonist of N-methyl-D-aspartate (NMDA)-type glutamate receptors that was approved for the treatment of moderate to severe Alzheimer's disease, has been negatively evaluated for the treatment of cognitive disorders of multiple sclerosis, but these studies were conducted only during short-term administration and on a heterogeneous group of patients with different forms of the disease. In addition, many adverse reactions were observed in these patients. AIMS: The purpose of the "EMERITE" (NCT01074619) study was to examine the efficacy and safety of the long-term administration of memantine as a symptomatic treatment for cognitive disorders in patients with relapsing remitting multiple sclerosis (RR-MS). METHODS: The study was supported by the French Ministry of Health and received additional support from Lundbeck. In this double-blind, placebo-controlled, parallel group, randomized trial, the participants were assigned to receive memantine (20 mg/day) or a placebo for 52 weeks. The participants included males and females, 18-60 years of age, with a diagnosis of RR-MS and presenting with a cognitive complaint and/or demonstrating moderate cognitive impairment. The data were collected in the Department of Neurology in 19 French centers. The primary outcome was the Paced Auditory Serial Addition Test (PASAT) score at week 52. Secondary measurements included additional neuropsychological tests and the annualized relapse rate. The scores were adjusted according to the baseline scores in the analysis. The safety was assessed by the number of adverse events. The random sequence was generated using the Excel software. At each center, only the pharmacist had access to the allocation sequence and could be asked to unblind the trial. RESULTS: Fifty patients were allocated to the memantine group, and 43 to the placebo group. The intent-to-treat (ITT) population included 31 patients in each group. After adjusting for the PASAT scores at baseline, the PASAT scores at the end point did not differ between the memantine and the placebo groups (p=0.88). Adjusted mean score difference (memantine minus placebo), was -0.40 (95% confidence interval: 5.5; +4.7). No significant differences were observed for the secondary outcomes (short term memory and attention scores, EDSS, and relapse rate). The findings remained unchanged after multiple imputation of the missing values. Neurological and psychiatric adverse events were significantly higher in the memantine group than in the placebo group, and these parameters were higher than those reported in the product literature of memantine. CONCLUSIONS: No differences between the placebo and memantine groups were observed. Nevertheless, the tolerability of memantine was significantly worse than expected. PMID- 27000225 TI - Rostral brain lesions of Leigh syndrome associated with the mitochondrial DNA 8993T>G mutation. PMID- 27000227 TI - Thioredoxin as a marker for severity and prognosis of aneurysmal subarachnoid hemorrhage. AB - OBJECTIVE: Circulating levels of thioredoxin (Trx), a potent anti-oxidant that modulates inflammation, cell growth and apoptosis, are increased in various critical care conditions. The purpose of this study was to establish the relationship between serum Trx levels and prognosis of aneurysmal subarachnoid hemorrhage (aSAH). METHODS: An enzyme-linked immunosorbent assay measurement of Trx was performed in serum from 132 patients and 132 healthy volunteers. Clinical outcomes included 6-month mortality and unfavorable outcome (Glasgow outcome scale score of 1-3). RESULTS: The serum Trx levels were significantly higher in patients than in controls (23.4+/-12.2 ng/mL vs.8.5+/-4.0 ng/mL, P<0.001) and had close relation to the World Federation of Neurological Surgeons (WFNS) scores (r=0.461, P<0.001) and modified Fisher scores (r=0.459, P<0.001). Trx was an independent predictor for 6-month mortality (Odds ratio, 1.386; 95% confidence interval, 1.015-2.161; P<0.001) and 6-month unfavorable outcome (Odds ratio, 1.297; 95% confidence interval, 1.012-2.002; P<0.001). Based on receiver operating characteristic curve, TRX had similar prognostic value compared with WFNS scores and modified Fisher scores and also significantly improved their prognostic value for 6-month unfavorable outcome, but not for 6-month mortality. CONCLUSIONS: Elevated plasma Trx levels are correlated with the severity and poor prognosis, substantializing Trx as a potential prognostic predictive biomarker following aSAH. PMID- 27000226 TI - Somatic CPEB4 and CPEB1 genes mutations spectrum on the prognostic predictive accuracy in patients with high-grade glioma and their clinical significance. AB - BACKGROUND: Glioblastoma (grade IV glioma/GBM) is characterized by extremely aggressive invasion and proliferative nature. OBJECTIVE: The main goal of this study was to evaluate the expression patterns of CPEB1 and CPEB4 in glioma patients. METHODS: 41 paraffin-embedded tissue samples with glioma (WHO I-IV) were collected between January 2008 and December 2012 in Tehran, Iran. MRI of patients was done before and within 24 h after surgery and gliomas investigated using quantitative real-time PCR and immunohistochemistry. Kaplan-Meier survival and Cox regression were applied to assess the prognosis of patients. RESULTS: The mRNA level of CPEB4 was strongly increased in tumor tissues (0.67+/-3.154 vs. 1.671+/-0.51; P=0.001). Furthermore, CPEB1 mRNA was significantly decreased in tumor tissues compared to normal tissues (2.852+/-0.587 vs. 1.471+/-0.862; P=0.025). Our findings showed that CPEB4 levels was markedly increased in patients with advanced grade gliomas (P=0.003). In addition, CPEB1 mRNA levels were not associated with clinicopathological features. Of the 41 cases, high CPEB4 expression was found in 29 patients (70.73%), while 12 cases (29.26%) showed weak expression levels, while the protein expression of CPEB4 were remarkably weak in normal tissues (P=0.001). However, no correlation was found between expression levels of CPEB1 and clinicopathological characteristics. Kaplan-Meier survival and log-rank test indicated that high expression of CPEB4 was correlated with shorter overall survival (log-rank test P<0.001). Furthermore, low expression of CPEB1 was linked to shorter overall survival (log rank test P=0.021). Multivariate Cox proportional hazards model showed that high CPEB1 (P=0.027), low CPEB4 expressions (P=0.021), and advanced tumor grade (P=0.036) were independent predictor of overall survival. CONCLUSION: Our data indicated expressions levels of CPEB4 and CPEB1 are correlated with overall survival in patients with glioma. PMID- 27000228 TI - The difference of apparent diffusion coefficient in the middle cerebellar peduncle among parkinsonian syndromes: Evidence from a meta-analysis. AB - The measurement of middle cerebellar peduncle (MCP) width allows for differential diagnosis between Parkinson's disease (PD) and multiple system atrophy with predominant parkinsonian features (MSA-P). However, it remains controversial whether apparent diffusion coefficient (ADC) value in the MCP of MSA-P is elevated or not. In the present study, we aimed to assess the usefulness of ADC value in the MCP for differential diagnosis between PD and MSA-P. An on-line literature search yielded 5 eligible studies. We expressed between-group difference of ADC value as the standardized mean difference (SMD). The proportion of variation due to heterogeneity was computed and expressed as I(2). ADC in the MCP of MSA-P was significantly increased compared with PD with heterogeneous studies (P=0.0007, I(2)=81%). A meta-regression analysis of MSA-P was conducted for "UPDRS III", and revealed a significant correlation between UPDRS III and SMD (P=0.01). Our meta-regression analysis has clarified the contribution of severity of MSA-P to heterogeneity of the included studies for ADC in the MCP. This finding raised the possibility that ADC in the MCP depended on severity of MSA-P, and less severe patients with MSA-P should be mainly enrolled in future study to assess the ability for differential diagnostic tool. PMID- 27000229 TI - Poly (ADP-ribose) polymerase-1 (PARP-1) -410C/T polymorphism in Sicilian patients with Parkinson's disease. PMID- 27000230 TI - Cerebrovascular reactivity after treatment of unruptured intracranial aneurysms- A transcranial Doppler sonography and acetazolamide study. AB - BACKGROUND: Cerebrovascular reactivity (CVR) is defined as the change in cerebral blood flow, or blood velocity, in response to a vasoactive stimulus. There is a possible association between impaired CVR and vasospasm after aneurysmal subarachnoid hemorrhage. Most studies on CVR and vasospasm have used healthy subjects as reference. However, due to potential different vascular features, CVR in persons with intracranial aneurysms may differ from CVR in healthy subjects. Therefore, our aim was to examine CVR in patients with unruptured intracranial aneurysms (UIA). METHODS: CVR was examined in 37 patients in the first postoperative week after treatment for UIA, using acetazolamide (AZ) test with transcranial Doppler monitoring of blood flow velocities. RESULTS: Mean blood flow velocity in the middle cerebral arteries was 58.5 (SD 12.8) cm/s at baseline, and 94.3 (SD 19.5) cm/s after stimulation with AZ. Mean CVR was 62.6 (SD 16.8) %. There was no significant difference when comparing right and left sides, and treated and untreated sides. A simple regression analysis suggested that CVR increased with 0.7% points for each year a patient aged (p=0.004). However, the significance disappeared in a multiple analysis (increase of 0.6% points per year, p=0.055). Other possible influencing factors (gender, smoking, hypertension, body mass index, aneurysm location and treatment modality) were not significantly associated with CVR. CONCLUSIONS: CVR in patients with UIA is not different from normal values reported in healthy subjects, and does not indicate a systemically impaired vascular system in patients with UIA. We suggest that CVR in age and gender matched healthy controls can be used as reference for persons with intracranial aneurysms. PMID- 27000231 TI - Closed-loop auditory feedback for the improvement of gait in patients with Parkinson's disease. AB - OBJECTIVE: To study the effects of closed-loop auditory feedback cues, corresponding to patient self-motion, on the walking abilities of patients with Parkinson's disease, in comparison to the effects of open-loop (metronome-like) auditory cues. METHODS: Sixteen patients on their regular medication schedule participated. A device which translates patient steps into a clicking cue sounded by earphones provides auditory feedback for gait pattern correction. Walking speed and stride length are measured. Device-on performance is compared to device off performance and to baseline performance, and short-term residual performance following 15 min rest is compared to baseline performance. RESULTS: Device-on performance was found to represent, on average, 10.72%+/-19.53% improvement in walking speed and 6.77%+/-6.57% improvement in stride length with respect to device-off performance, and an average improvement of 12.37%+/-18.37% in walking speed and 4.30%+/-3.64% in stride length with respect to baseline performance, with 87.5% and 81.25% of the patients improving their walking speed and stride length, respectively. Average short-term residual performance showed 9.09%+/ 6.34% improvement in walking speed and 6.52%+/-4.36% improvement in stride length, compared to baseline performance, with 85.71% of the patients improving in both walking speed and stride length. CONCLUSIONS: Closed-loop auditory feedback improves walking speed and stride length in patients with Parkinson's disease. Improvement in walking speed is more pronounced than improvement in stride length. Yet, in contrast to previously studied open-loop auditory cues, training with closed-loop auditory feedback results in non-negligible on-line improvement in stride length. Moreover, in contrast to previously reported results of open-loop auditory cuing, training with closed-loop auditory feedback has residual effects, which suggest the examination of this approach in a comprehensive therapy program. PMID- 27000233 TI - Late onset Huntington's disease with 29 CAG repeat expansion. PMID- 27000232 TI - Association of IL4 and IL4R polymorphisms with multiple sclerosis susceptibility in Caucasian population: A meta-analysis. AB - BACKGROUND: Previous studies have suggested a role for interleukin-4 (IL4) and its receptor (IL4R) gene in susceptibility to multiple sclerosis (MS), but the results remain controversial and under-powered. OBJECTIVES: To investigate the contradictory results, we performed a meta-analysis to assess the possible association between polymorphisms of the IL4 rs2243250 (C/T), variable number of tandem repeat (VNTR) polymorphism in intron-3 (I3(709)VNTR), IL4R rs1801275 (T/C) and MS in Caucasian populations. METHODS: A comprehensive search was conducted to identify all case-control or cohort design studies. The fixed or random effect pooled measure was selected based on the homogeneity test among studies that was evaluated with I(2). Publication bias was estimated using the Begg's and Egger's test. RESULTS: A total of ten studies were included in the meta-analysis. The crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to evaluate the association. Overall, after excluding articles deviating from Hardy Weinberg equilibrium in controls and sensitive analysis, the meta-analysis showed a significant association between polymorphism of IL4 rs2243250 and MS susceptibility in allele model (OR=1.209, 95% CI=1.022-1.429, P=0.026) and dominant model (OR =1.225, 95% CI=1.013-1.480, P=0.036). However, no significant association was found between polymorphisms of IL4 I3(709)*VNTR, IL4R rs1801275 and MS susceptibility, respectively. CONCLUSIONS: The meta-analysis indicates that the T allele, CT and TT genotype of polymorphism of IL4 rs2243250 (C/T) may reduce the risk of MS in Caucasian populations, while polymorphisms of IL4 I3(709)*VNTR and IL4R rs1801275 may not associated with risk of MS in Caucasian populations. PMID- 27000234 TI - HLA-DRB1*14 and DQB1*05 are associated with Japanese anti-MuSK antibody-positive myasthenia gravis patients. AB - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder presumed to be associated with genetic susceptibility. This study aims to determine whether HLA is associated with MG in Japanese patients. METHODS: We included 58 MG patients with anti-acetylcholine receptor antibody (AChR+MG) and 14 MG patients with muscle-specific receptor tyrosine kinase (MuSK+MG) and determined HLA-A, B, DRB1 and -DQB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide and primers. AChR+MG was classified into the three subgroups: early-onset MG (EOMG; n=11), late-onset MG (LOMG; n=20), and thymoma-associated MG (n=27). Healthy volunteers (n=100) served as controls. RESULTS: A significant positive association was observed between MuSK+MG with the DRB1*14 [57.1%, MuSK+MG vs. 18.0%, healthy controls (HC); odds ratio (OR): 6.1] and DQB1*05 [78.6%, MuSK+MG vs. 30.0%, HC; odds ratio (OR): 8.5]. We found a negative association between LOMG and DQB1*04 [5.0%, LOMG vs. 37.0%, HC; OR: 0.09]. There was no association between other MG subgroups and HLA alleles. CONCLUSION: HLA DRB1*14 and DQB1*05 were associated with MuSK+MG, therefore these alleles may play important roles in developing MuSK+MG across the races. PMID- 27000235 TI - Trends in scientific publishing: Dark clouds loom large. AB - The world wide web has brought about a paradigm shift in the way medical research is published and accessed. The ease with which a new journal can be started/hosted by publishing start-ups is unprecedented. The tremendous capabilities of the world wide web and the open access revolution when combined with a highly profitable business have attracted unscrupulous fraudulent operators to the publishing industry. The intent of these fraudulent publishers is solely driven by profit with utter disregard to scientific content, peer reviews and ethics. This phenomenon has been referred to as "predatory publishing". The "international" tag of such journals often betrays their true origins. The gold open access model of publishing, where the author pays the publisher, when coupled with a non-existent peer review threatens to blur the distinction between science and pseudoscience. The average researcher needs to be made more aware of this clear and present danger to the scientific community. Prevention is better than cure. PMID- 27000236 TI - Diagnostic ability of 3-dimensional contrast-enhanced MR angiography in identifying vertebral basilar artery stenosis. AB - BACKGROUND: Vertebral-basilar artery stenosis is associated with posterior circulation infarction. So correct detection of vertebral basilar artery stenosis is very important. Studies concerning the sensitivity and specificity of 3 dimensional contrast enhanced MR angiography (3D-CE-MRA) in detecting vertebral basilar artery stenosis is generally lacking. METHODS: Retrospectively reviewed the imagines of consecutive one hundred and forty-nine Chinese patients with ischemic stroke or vertigo/dizziness who underwent 3D-CE-MRA and DSA. DSA and CE MRA images were studied separately and to determine the presence of mild, moderate, or severe stenosis of the vertebral-basilar arteries. Analysis combined with vascular origin image was applied when evaluating the vertebral artery origin stenosis. Sensitivity, specificity, positive and negative predictive values, and the accuracy of 3D-CE-MRA in detecting and grading of vertebral basilar artery stenosis were calculated. RESULTS: Compared with DSA, sensitivity, specificity and accuracy of 3D-CE-MRA in detecting of vertebral artery origin >=70% stenosis or occlusion was 97.1%, 77.4% and 81.9%, but diagnostic consistency was poor (K=0.59); Analysis combined with vascular origin images, the specificity (97.8%), accuracy (92.9%) and consistency (K=0.826) was significantly improved. CONCLUSIONS: 3D-CE-MRA is a sensitive and noninvasive technique for the detection of vertebral artery origin stenosis. Furthermore, analysis combined with vascular origin image would improve the diagnostic accuracy. PMID- 27000237 TI - Selective impairment of attention networks during propofol anesthesia after gynecological surgery in middle-aged women. AB - BACKGROUND: Postoperative cognitive dysfunction is a common complication of anesthesia and surgery. Attention networks are essential components of cognitive function and are subject to impairment after anesthesia and surgery. It is not known whether such impairment represents a global attention deficit or relates to a specific attention network. We used an Attention Network Task (ANT) to examine the efficiency of the alerting, orienting, and executive control attention networks in middle-aged women (40-60 years) undergoing gynecologic surgery. A matched group of medical inpatients were recruited as a control. METHODS: Fifty female patients undergoing gynecologic surgery (observation group) and 50 female medical inpatients (control group) participated in this study. Preoperatively patients were administered a mini-mental state examination as a screening method. The preoperative efficiencies of three attention networks in an attention network test were compared to the 1st and 5th post-operative days. RESULTS: The control group did not have any significant attention network impairments. On the 1st postoperative day, significant impairment was shown in the alerting (p=0.003 vs. control group, p=0.015 vs. baseline), orienting (p<0.001 vs. both baseline level and control group), and executive control networks (p=0.007 vs. control group, p=0.002 vs. baseline) of the observation group. By the 5th postoperative day, the alerting network efficiency had recovered to preoperative levels (p=0.464 vs. baseline) and the orienting network efficiency had recovered partially (p=0.031 vs. 1st post-operative day), but not to preoperative levels (p=0.01 vs. baseline). The executive control network did not recover by the 5th postoperative day (p=0.001 vs. baseline, p=0.680 vs. 1st post-operative day). CONCLUSIONS: Attention networks of middle-aged women show a varying degree of significant impairment and differing levels of recovery after surgery and propofol anesthetic. PMID- 27000238 TI - Effect of reading on blood flow changes in the posterior cerebral artery in early blind and sighted people--A transcranial Doppler study. AB - BACKGROUND: Neuroimaging studies proved that Braille reading resulted in visual cortex activation in blind people, however, very few data are available about the measure of flow increase in these subjects. Therefore, we investigated the flow response in the posterior cerebral artery (PCA) of eleven early blind and ten sighted subjects induced by reading Braille and print, respectively. METHODS: Two experimental protocols were used in both groups: PCA flow velocity during reading was compared to the resting phase and "NLC" phase (volunteers "read" non-lexical characters; e.g. .,-.:,-.:...,). The use of these experimental protocols allowed to investigate separately the effect of "light stimulus+print reading" versus "print reading alone" in sighted, and "hand/finger movement+Braille reading" versus "Braille reading alone" in blind subjects. RESULTS: The flow response in the PCA evoked by "Braille reading alone" in blind (10.5+/-4.5%) and "print reading alone" in sighted subjects (8.1+/-3.5%) was similar. The flow increase induced by "hand/finger movement+Braille reading" and by "Braille reading alone" did not differ in blind people, however, "light stimulus+print reading" in sighted subjects caused higher PCA flow increase (25.9+/-6.9%) than "print reading alone" (8.1+/-3.5%). CONCLUSION: The similar PCA flow response induced by Braille and print reading alone suggested a similar degree of occipital cortex activation in blind and sighted subjects. In sighted people, the 3-times higher flow velocity increase induced by "light stimulus+print reading" compared with "print reading alone" indicated that 2/3 of PCA flow increase during reading was due to the light stimulus and only 1/3 of flow response was caused by reading alone. PMID- 27000239 TI - Xenon depresses aEEG background voltage activity whilst maintaining cardiovascular stability in sedated healthy newborn pigs. AB - BACKGROUND: Changes in electroencephalography (EEG) voltage range are used to monitor the depth of anaesthesia, as well as predict outcome after hypoxia ischaemia in neonates. Xenon is being investigated as a potential neuroprotectant after hypoxic-ischaemic brain injury, but the effect of Xenon on EEG parameters in children or neonates is not known. This study aimed to examine the effect of 50% inhaled Xenon on background amplitude-integrated EEG (aEEG) activity in sedated healthy newborn pigs. METHODS: Five healthy newborn pigs, receiving intravenous fentanyl sedation, were ventilated for 24 h with 50%Xenon, 30%O2 and 20%N2 at normothermia. The upper and lower voltage-range of the aEEG was continuously monitored together with cardiovascular parameters throughout a 1 h baseline period with fentanyl sedation only, followed by 24 h of Xenon administration. RESULTS: The median (IQR) upper and lower aEEG voltage during 1 h baseline was 48.0 MUV (46.0-50.0) and 25.0 MUV (23.0-26.0), respectively. The median (IQR) aEEG upper and lower voltage ranges were significantly depressed to 21.5 MUV (20.0-26.5) and 12.0 MUV (12.0-16.5) from 10 min after the onset of 50% Xenon administration (p=0.002). After the initial Xenon induced depression in background aEEG voltage, no further aEEG changes were seen over the following 24h of ventilation with 50% xenon under fentanyl sedation. Mean arterial blood pressure and heart rate remained stable. CONCLUSION: Mean arterial blood pressure and heart rate were not significantly influenced by 24h Xenon ventilation. 50% Xenon rapidly depresses background aEEG voltage to a steady ~50% lower level in sedated healthy newborn pigs. Therefore, care must be taken when interpreting the background voltage in neonates also receiving Xenon. PMID- 27000240 TI - Liposarcoma concurrence in a multiple sclerosis patient treated with interferon beta 1b. PMID- 27000241 TI - Regulation of P-glycoprotein efflux activity by Z-guggulsterone of Commiphora mukul at the blood-brain barrier. AB - The present study was to investigate whether Z-guggulsterone had the regulatory effect on the activity and expression of P-glycoprotein in rat brain microvessel endothelial cells (rBMECs) and in rat brain. Inorganic phosphate liberation assay, high performance liquid chromatography, and western blot analysis were performed to assess the P-glycoprotein ATPase activity, the accumulation of NaF and rhodamine 123, and P-glycoprotein and MRP1 expression. The results showed that Z-guggulsterone (0-100 MUM) significantly enhanced basal P-glycoprotein ATPase activity in a concentration-dependent manner. Tetrandrine (0.1, 0.3, 1 MUM) or cyclosporine A (0.1, 0.3, 1 MUM) had non-competitively inhibitory manner on Z-guggulsterone-stimulated P-glycoprotein ATPase activity, suggesting that Z guggulsterone might have unique binding site or regulating site on P glycoprotein. However, Z-guggulsterone (30, 100 MUM) had almost no influence on MRP1 expression in rBMECs. Further results revealed that Z-guggulsterone (50mg/kg) significantly increased the accumulation of rhodamine 123 by down regulating P-glycoprotein expression in rat brain, as compared with control (P<0.05). Our studies suggested that Z-guggulsterone potentially inhibited the activity and expression of P-glycoprotein in rBMECs and in rat brain. PMID- 27000242 TI - Gut microbiota composition and relapse risk in pediatric MS: A pilot study. AB - We explored the association between baseline gut microbiota (16S rRNA biomarker sequencing of stool samples) in 17 relapsing-remitting pediatric MS cases and risk of relapse over a mean 19.8 months follow-up. From the Kaplan-Meier curve, 25% relapsed within an estimated 166 days from baseline. A shorter time to relapse was associated with Fusobacteria depletion (p=0.001 log-rank test), expansion of the Firmicutes (p=0.003), and presence of the Archaea Euryarchaeota (p=0.037). After covariate adjustments for age and immunomodulatory drug exposure, only absence (vs. presence) of Fusobacteria was associated with relapse risk (hazard ratio=3.2 (95% CI: 1.2-9.0), p=0.024). Further investigation is warranted. Findings could offer new targets to alter the MS disease course. PMID- 27000243 TI - Serum neuron specific enolase could predict subclinical brain damage and the subsequent occurrence of brain related vascular events during follow up in essential hypertension. AB - The object of this work was to explore if blood based biomarkers of brain damage could predict subclinical brain lesions and clinical outcome during follow-up in asymptomatic hypertensive patients. This was a cross-sectional study including 101 patients with essential hypertension and no clinical evidence of neurological disease and 53 healthy controls, followed by a longitudinal study of 62 hypertensive patients for an average of 33 months. Serum concentrations of two brain specific proteins (S100B and neuron specific enolase - NSE) were determined at inclusion. Fundoscopic exploration, brain MRI and echocardiographic studies were also performed. Clinical outcome at follow-up was registered: transient ischemic attack (TIA), stroke, vascular headache or migraine, cardiovascular events and death. Higher serum NSE and S100B concentrations were observed in hypertensive patients; and multiple regression analysis revealed independent associations of clinical variables and more severe white matter lesions only with NSE concentration. A panel combining two clinical variables (blood pressure>140/90 and years of hypertension>10) and serum NSE>13 MUg/L predicted more severe white matter lesions with 80% sensitivity and 94.4% specificity. Higher NSE levels at inclusion were associated not only with the occurrence of vascular events related with the CNS (stroke, TIA and vascular headache), but also with an earlier presentation of these events during the follow-up period. Serum NSE concentration could be a useful biomarker to predict subclinical brain damage and future vascular events related with the CNS in hypertension. Blood based biomarkers could aid in filtering hypertensive patients with a higher risk of cerebrovascular disease for brain MRI scanning. PMID- 27000244 TI - Neurologists and Zika. PMID- 27000245 TI - Sequencing analysis of the human glucocorticoid receptor (NR3C1) gene in multiple sclerosis patients. AB - Various specific human glucocorticoid receptor (NR3C1) gene polymorphisms have been described in multiple sclerosis (MS) patients and correlated with disease progression, susceptibility and aggressiveness. Herein, we investigated the presence of gene alterations in the entire coding region of the NR3C1 in MS patients of variable clinical status (CIS, RRMS and SPMS) and the association(s) of these alterations with severity of disease (EDSS), response to glucocorticoid (GC) treatment and clinical improvement. Sixty Caucasian Greek MS patients were included. Sequencing the coding sequences and intron-exon boundaries of the NR3C1 did not reveal the presence of mutation(s) in any of the MS patients. Three previously described polymorphisms were detected: p.N363S (rs6195), p.N766N (rs6196) and c.1469-16G>T (rs6188). None of the identified alleles/genotypes were found to be associated with the severity of disease, response to glucocorticoids and disease subtypes. Known polymorphism, such as ER22/23EK that has been previously detected in MS patients, was not detected. There is a considerable ethnicity-related variation in the frequency of the NR3C1 polymorphisms. Although a genetic basis of the glucocorticoid sensitivity exists in healthy population, in the presence of chronic inflammation and abundance of cytokines--such in MS patients--other factors appear to play a more important role in GC sensitivity. PMID- 27000246 TI - A clinical study on closing-in in focal brain-damaged individuals. AB - In visuo-constructional assessment, brain-damaged individuals may copy figures near to or superimposed on the model, showing the Closing-in (CI). CI has been largely investigated in dementia, and often ascribed to impairments of the attention/executive abilities ("Attraction hypothesis"). Only a few dated studies investigated frequency of CI in brain-damaged individuals, without clarifying the genesis of the phenomenon. We aimed at testing the "Attraction hypothesis" in 27 individuals with focal frontal cortical or sub-cortical brain lesions by a dual task experimental paradigm. The participants underwent a neuropsychological battery and a copying task to be performed alone (single task condition), or concurrently with a simple or a complex verbal secondary task (dual-task conditions). CI was found in 66% of frontal-damaged individuals, who scored significantly lower than healthy adults on all neuropsychological measures; brain damaged individuals showing CI performed worse than frontal-damaged individuals without CI on frontal and visuo-constructional measures. In the dual-task condition with the complex secondary task CI was significantly enhanced, with a weaker tendency to self-correction, in individuals with CI compared to individuals without CI. These findings would confirm that the CI in brain-damaged individuals is related to reduction of attentional resources, consistently with the "Attraction hypothesis". PMID- 27000247 TI - Upregulation of spinal NMDA receptors mediates hydrogen sulfide-induced hyperalgesia. AB - Hydrogen sulfide (H2S) is an endogenous neurotransmitter that importantly regulates various physiological and pathological events including pain signal transduction. In this study, we investigated the role of spinal NMDA receptors in the nociception induced by intraplantar injection of NaHS, an H2S donor. Intraplantar injection of NaHS into hindpaw significantly decreased the paw withdrawal threshold (PWT) in contralateral hindpaw. However, intraplantar formalin injection did not produce PWT in contralateral hindpaw. Intrathecal injection of methemoglobin, a H2S scavenger, abolished hyperalgesia induced by NaHS. In addition, NaHS-induced hyperalgesia was partly, but significantly, attenuated by intrathecal injection of hydroxylamine, a cystathionine-beta synthase (CBS) inhibitor. RT-PCR and western blotting analysis revealed that NR2B mRNA and protein levels were increased in the spinal dorsal horn, but not in dorsal root ganglion (DRG) in rats subjected to NaHS intraplantar injection. Collectively, these data suggest that peripheral injection of H2S donor causes hyperalgesia through increase in NR2B expression and production of H2S in the spinal cord. PMID- 27000249 TI - Alemtuzumab improves neurological functional systems in treatment-naive relapsing remitting multiple sclerosis patients. AB - BACKGROUND: Individual functional system scores (FSS) of the Expanded Disability Status Scale (EDSS) play a central role in determining the overall EDSS score in patients with early-stage multiple sclerosis (MS). Alemtuzumab treatment improves preexisting disability for many patients; however, it is unknown whether improvement is specific to certain functional systems. OBJECTIVE: We assessed the effect of alemtuzumab on individual FSS of the EDSS. METHODS: CAMMS223 was a 36 month, rater-blinded, phase 2 trial; treatment-naive patients with active relapsing-remitting MS, EDSS <=3, and symptom onset within 3 years were randomized to annual courses of alemtuzumab or subcutaneous interferon beta-1a (SC IFNB-1a) 44 MUg three times weekly. RESULTS: Alemtuzumab-treated patients had improved outcomes versus SC IFNB-1a patients on most FSS at Month 36; the greatest effect occurred for sensory, pyramidal, and cerebellar FSS. Among patients who experienced 6-month sustained accumulation of disability, clinical worsening occurred most frequently in the brainstem and sensory systems. For patients with 6-month sustained reduction in preexisting disability, pyramidal and sensory systems contributed most frequently to clinical improvement. CONCLUSIONS: Alemtuzumab demonstrated a broad treatment effect in improving preexisting disability. These findings may influence treatment decisions in patients with early, active relapsing-remitting MS displaying neurological deficits. ClinicalTrials.gov Identifier NCT00050778. PMID- 27000248 TI - Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment. AB - Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain Barre syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown. PMID- 27000250 TI - Intracerebral hemorrhage in patients after heart valve replacement. AB - BACKGROUNDS: Although prevention of hematoma enlargement and thromboembolic complications is critically important in acute intracerebral hemorrhage (ICH) patients with prosthetic heart valves, clinical data are scarce. The goal of this study was to elucidate patient characteristics, acute treatments, and the clinical course of them. METHODS: We investigated a retrospective cohort of consecutive acute ICH patients with prosthetic heart valves. Neurological data, hospital management, hemorrhagic and thromboembolic complications and functional disability/mortality were reviewed. RESULTS: We identified 38 patients (27 men; 67.9+/-16.7 years). The median ICH volume was 22.8 ml. The most frequent location was lobar (50%). All patients with mechanical valves (25/25) and 46% of patients with bioprosthetic valves (6/13) were receiving warfarin at the time of hospital admission. The median anticoagulation withholding period was 2 days in 24 patients who ultimately resumed anticoagulation. Hematoma enlargement within 24 h was observed in eight patients and hemorrhagic complications occurred in three patients. Thromboembolic stroke occurred in four patients. At discharge, death had occurred or severe disability was present in 53% of patients (20/38). CONCLUSIONS: Hematoma enlargement, hemorrhagic complications or thromboembolic stroke occurred in a significant number of patients during hospitalization. ICH was a serious complication among patients with valve replacement. PMID- 27000251 TI - Role of glyoxalase I gene polymorphisms in late-onset epilepsy and drug-resistant epilepsy. AB - BACKGROUND: Recent studies indicate that increased expression of glyoxalase I (GLO1) could result in epileptic seizures; thus, this study further explored the association of GLO1 with epilepsy from the perspective of molecular genetics. MATERIAL AND METHODS: GLO1 single nucleotide polymorphisms (SNPs; rs1130534, rs4746 and rs1049346) were investigated in cohort I (the initial samples: 249 cases and 289 controls). A replication study designed to confirm the positive findings in cohort I was performed in cohorts II (the additional samples: 130 cases and 191 controls) and I+II. RESULTS: In cohorts I, II and I+II, the CC genotype at rs1049346 T>C exerts a protective effect against both late-onset epilepsy (odds ratio [OR]=2.437, p=0.013; OR=2.844, p=0.008; OR=2.645, p=0.000, q=0.003, respectively) and drug-resistant epilepsy (DRE) (OR=2.985, p=0.020; OR=2.943, p=0.014; OR=3.049, p=0.001, q=0.006, respectively). Further analyses in cohort I+II indicate that the presence of the TAC/AAT haplotypes (rs1130534 rs4746-rs1049346) may be used as a marker of predisposition to/protection against DRE (p=0.002, q=0.010; p=0.000, q=0.002, respectively). CONCLUSIONS: This study is the first to demonstrate that the GLO1 SNPs are significantly associated with epilepsy. In particular, the rs1049346 T>C SNPs are potentially useful for risk assessment of late-onset epilepsy and DRE. PMID- 27000252 TI - Magnetic resonance imaging biomarkers indicate a central venous hypertension syndrome in patients with symptomatic pineal cysts. AB - BACKGROUND: While most pineal cysts (PCs) are asymptomatic, some PCs are accompanied with symptoms of variable severity. We suggested that symptom severity in symptomatic patients with non-hydrocephalic PCs relates to venous compression causing central venous hypertension. This study explored whether possible magnetic resonance imaging (MRI) biomarkers of central venous hypertension could differentiate the severity of symptoms in individuals with non hydrocephalic PCs. METHODS: The study included all individuals with PCs and MRI available for analysis followed conservatively within the department from 2003 to 2014. Severity of symptoms at follow-up were assessed from a questionnaire. Suggested MRI biomarkers indicative of central venous hypertension were explored, in addition to MRI measures of cyst size, aqueduct stenosis, and tectal compression. RESULTS: The study included 66 patients. As compared to the 27/66 patients (41%) with "None-Moderate" symptoms at follow-up, the 39/66 patients (59%) with "Much-Severe" symptoms presented with significantly altered indices of central venous hypertension (tectum-splenium-cyst ratio and indices of thalamic and periventricular edema). PC grading based on MRI biomarkers of central venous hypertension differentiated the severity of symptoms. CONCLUSION: The results indicate an association between severity of symptoms and MRI biomarkers of central venous hypertension in symptomatic individuals with non-hydrocephalic PCs. PMID- 27000253 TI - Recent patterns and predictors of neurological mortality among hospitalized patients in Central Ghana. AB - BACKGROUND: Although neurological disorders are projected to escalate globally in the coming decades, there is a paucity of enumerated data on the burden, spectrum and determinants of outcomes of adult neurological admissions in resource-limited settings, especially within sub-Saharan Africa. OBJECTIVE: To evaluate the diversity, demography, and determinants of mortality among adult patients presenting with neurological disorders over a 6-year period in a tertiary medical referral institution in the Central belt of Ghana. METHODS: A retrospective analysis of data on neurological admissions and in-patient outcomes between 2008 and 2013 was undertaken. Data collected for analyses included age, gender, neurological diagnosis, documented comorbidities, duration of admission and vital status at discharge. Predictors of in-patient mortality were evaluated using Kaplan-Meier survival curves and Cox Proportional Hazards regression models. RESULTS: The 6494 admissions with neurological disorders represented 15.0% of all adult medical admissions over the study period. Male-to-female ratio of admissions was 1.6:1.0 with a mean+/-SD age of 52.9+/-20 years. The commonest neurological disorders were Cerebrovascular, Infectious, Seizures/epilepsy, Alcohol-use and Spinal cord disorders representing 54.0%, 26.7%, 10.3%, 4.0% and 2.3% of admissions respectively. Despite the low national HIV prevalence of 2.0%, the frequency of HIV infection among patients with infectious disorders of the nervous system was 40.9%. Overall crude mortality rate for neurologic admissions was 30.6% being 39.1% and 33.9% for Infectious affectations of the nervous system and stroke respectively and 7.4% for seizure disorders. Probability of death was higher for females than males aHR (95% CI) of 1.53 (1.40-1.68) and increasing age aHR (95% CI) of 1.11 (1.06-1.17) for each 20-year increase in age. CONCLUSION: Almost one in three patients admitted with neurological disease to a tertiary care center in Ghana died in the hospital, and the majority of these deaths were due to non-communicable conditions. Enhanced multi-dimensional public health disease prevention strategies and neurological inpatient care processes are warranted. PMID- 27000254 TI - Diffusion tensor imaging of the corticospinal tract and walking performance in multiple sclerosis. AB - Research has identified a significant relationship between DTI (Diffusion Tensor Imaging) indices in the Corticospinal Tract (CST) and disability status in persons with multiple sclerosis (MS). To date, there is little known about the association between DTI indices of the CST with walking and gait outcomes in MS. This study examined the associations among DTI indices [fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD)] of the CST with walking and gait outcomes in persons with MS. We enrolled 69 persons with MS who underwent 3T brain magnetic resonance imaging (MRI) and examined white matter structural integrity in the CST in the brain with DTI. Participants completed three walking performance assessments: 6-minute walk (6MW), timed 25-foot walk (T25FW), and gait testing. We examined associations using Spearman (r(s)) and partial Spearman correlation (pr(s)) analyses, using the entire sample and stratifying by disability status after controlling for age and sex. After controlling for age, sex, and disease duration, RD was significantly correlated (p<0.05) with step time (pr(s)=0.30). AD was significantly correlated (p<0.05) with step length (pr(s)=-0.32). MD was significantly associated (p<0.05) with 6MW (pr(s)=-0.35), T25FW (pr(s)=-0.34), gait velocity (pr(s)=-0.31), step time (pr(s)=0.29), and step length (pr(s)=-0.36). FA was not significantly correlated with any of the walking parameters (p>0.05). We provide novel evidence of possible motor pathway damage involved in walking performance in MS. There may be subtle differences in associations between MD, AD, and RD with walking outcomes, and these could be assessed in future longitudinal examinations and clinical trials of motor rehabilitation. PMID- 27000255 TI - Risk score to predict concurrent extracranial and intracranial artery stenosis in acute ischemic stroke. AB - OBJECTIVE: The aim of this study was to develop and validate a risk score for predicting combined extracranial and intracranial artery stenosis (EICAS) in acute ischemic stroke patients. METHODS: Patients with acute ischemic stroke were consecutively and prospectively enrolled in this study. Eligible patients were randomly divided into derivation and validation cohorts. Variables collected at presentation were used for predicting EICAS after acute ischemic stroke. Multivariable logistic regression was used to identify independent risk factors. Points for EICAS were generated by beta-coefficients. Sensitivity and specificity of the risk score was assessed by the area under the receiver operating characteristic curve (AUROC). Cutoff value for predicting EICAS was determined by maximum Youden index. RESULTS: There were 629 patients with EICAS and 352 patients without cranial artery stenosis. Among EICAS, 321 patients were in the derivation cohort and 308 in the validation cohort. Five independent predictors including age, diabetes mellitus, hypertension, Low density lipoprotein (LDL) and heart disease were used to develop a 10-point score. The score was termed ADLH2 (age, diabetes mellitus, hypertension, LDL, heart disease).The ADLH2 showed good discrimination in the derivation (AUROC 0.695; 95% confidence interval, 0.656 0.735) and validation (AUROC 0.672; 95% confidence interval, 0.631-0.712) cohort. The cutoff value at maximum Youden index was 4 with the sensitivity 0.479 and specificity 0.719. Stroke patients with ADLH2 score>=4 need further examination and therapy for EICAS. CONCLUSIONS: The ADLH2 score is a valid risk score to identify high-risk EICAS individuals who need further investigation and treatment. PMID- 27000256 TI - Hypovitaminosis D association with disease activity in relapsing remitting multiple sclerosis in Brazil. AB - Multiple sclerosis (MS) onset is believed to result from a combination of environmental and genetic factors. A prevailing theory addresses the influence of hypovitaminosis D in the development of MS. This research aimed to study the association between vitamin D serum levels and MS, as a prognostic and risk factor for the development and progression of the disease. A cross-sectional multicenter study was conducted in patients with relapsing-remitting MS (n=67), according to the revised McDonald criteria (2010), accompanied in three MS centers in different Brazilian states. A control group consisted of healthy volunteers (n=61). Blood collections were carried out in late summer and late winter. This seems to be the first study of this kind in Latin America. The vitamin D serum levels for MS patients (29.63+/-8.08) in summer were similar to the controls (29.71+/-8.28); however, in winter they were lower than the healthy individuals (24.05+/-7.47 vs 26.56+/-8.01). No significant difference between the three cities was observed. No association was noted between vitamin D serum levels and gender, race and age, nor correlation of these levels with the EDSS or disease duration. In contrast, a significant association was seen between deficient vitamin D serum levels in late winter with disease activity, characterized by the onset of relapses (19.73+/-5.69 vs 25.30+/-6.22) or Gd+ lesions (17.22+/-3.11 vs 22.79+/-7.22). PMID- 27000257 TI - The alkylglycerol monooxygenase (AGMO) gene previously involved in autism also causes a novel syndromic form of primary microcephaly in a consanguineous Saudi family. AB - Autosomal recessive primary microcephaly (MCPH) refers to a genetically heterogeneous group of neurodevelopmental disorders in which patients exhibit a marked decrease in occipitofrontal head circumference at birth and a variable degree of intellectual disability. To date, 18 genes have been reported for MCPH worldwide. We enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. Whole exome sequencing (WES) with 100* coverage was performed on two affected siblings after defining common regions of homozygosity through genome wide single nucleotide polymorphism (SNP) microarray genotyping. WES data analysis, confirmed by subsequent Sanger sequence validation, identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase (AGMO) gene on chromosome 7p21.2. Population screening of 178 ethnically matched control chromosomes and consultation of the Exome Aggregation Consortium database, containing 60,706 individuals' exomes worldwide, confirmed that this mutation was not present outside the family. To the best of our knowledge, this is the first evidence of an AGMO mutation underlying primary microcephaly and intellectual disability in humans. Our findings further expand the genetic heterogeneity of MCPH in familial cases. PMID- 27000258 TI - ALS patients with ability to communicate after long-term mechanical ventilation have confined degeneration to the motor neuron system. AB - OBJECTIVE: To clarify the position in the amyotrophic lateral sclerosis (ALS) spectrum, of a subgroup of patients who maintained the ability to communicate after long-term mechanical ventilation (LTMV) by tracheostomy. METHODS: We undertook a clinicopathological investigation of sporadic ALS in three patients who maintained the ability to communicate after approximately 30-year survival on LTMV by tracheostomy. RESULTS: The age of onset and duration of disease was 48 years and 31 years in patient 1, 55 years and 29 years in patient 2, and 31 years and 33 years in patient 3, respectively. Each patient displayed slow disease progression. In all patients, both upper and lower motor neurons were markedly degenerated, while other neuronal systems and the brainstem tegmentum were spared. A few normal-looking motor neurons remained in the anterior horn of the spinal cord. There were no TAR DNA-binding protein 43-immunoreactive inclusions in the lower motor neurons in any patient and only occasional inclusions in the cerebral cortex of one patient. CONCLUSION: The clinicopathological findings of these three patients suggest that there is a distinct subgroup of ALS patients characterized by the above-mentioned features. PMID- 27000260 TI - A DWI study of the contralateral hemisphere in cerebral hemiatrophy. AB - BACKGROUND AND AIM: Cerebral hemiatrophy (CHA) is a congenital or acquired loss of volume in one hemisphere of the brain. The MR findings of the affected hemisphere have been a subject of many studies, however, the contralateral hemisphere has not been investigated. There is, in fact, an integrity between two hemispheres of the brain through transverse connection fibers. The aim of this study is to investigate the changes in the contralateral hemisphere in CHA. MATERIALS AND METHODS: Apparent diffusion coefficient (ADC) values were measured in deep gray and white matter areas in the normal-appearing contralateral hemisphere in 23 patients with CHA, in order to get in vivo information about a possible Wallerian degeneration or microstructural changes. Results were compared with the control group. RESULTS: Normal ADC values were encountered in the contralateral hemisphere in all (100%) CHA patients. The difference between the ADC values of gray and white matter in CHA patients and the control group was not statistically significant. CONCLUSION: Normal ADC values in the contralateral hemisphere in CHA patients suggests a compensatory mechanism restricting Wallerian degeneration or diffusion alteration. PMID- 27000259 TI - Overexpression of ubiquitin-specific protease 2a (USP2a) and nuclear factor erythroid 2-related factor 2 (Nrf2) in human gliomas. AB - BACKGROUND: Gliomas are among the most frequent adult primary brain tumors. Recent studies have shown that there are novel opportunities for developing therapeutics by targeting the differentiation and self-renewal features of glioma. OBJECTIVE: The aim of this study was to evaluate the expression levels of USP2a an Nrf2 in patients with glioma and their association with prognosis of gliomas that was detected with immunohistochemical staining. METHODS: In this study, 40 patient's tissue samples with primary gliomas were collected between January 2009 and December 2013. MRI of patients was done before and within 24 h after surgery. USP2a and Nrf2 expression levels were examined by immunohistochemistry. Data were analyzed using the SPSS 16.0, X(2) test, log-rank test and Kaplan-Meier method. RESULTS: Immunohistochemistry indicated that USP2a expression was increased in glioma cells than normal brain tissues. The increased USP2a staining was markedly correlated with advanced tumor grade (P=0.02) and age (P=0.016). Our result showed that Nrf2 expression was significantly higher in glioma cells as compared to normal brain tissues. The high expression level of Nrf2 was markedly linked to age (P=0.007), and tumor grade (P=0.03). Kaplan-Meier survival and log-rank analysis indicated that patients with low expression of USP2a had longer overall survival than those with high levels (log-rank test P<0.001). Moreover, patients with high Nrf2 expression had shorter overall survival than those with low levels (log-rank test P<0.001). In the univariate analysis, the high expression of Nrf2 and USP2a (P=0.004; P=0.006), age (P=0.025), and tumor grade (P=0.001) were correlated with poor survival. Multivariate Cox proportional hazards model indicated that, high Nrf2 and USP2a staining (P=0.001; P=0.003), advanced tumor grade (P=0.01) and age (P=0.033) were independent predictor of overall survival. CONCLUSION: In summary, the result of this study showed USP2a and Nrf2 may be as prognostic marker in patients with gliomas. PMID- 27000261 TI - Antimicrobial activity of the pygidial gland secretion of three ground beetle species (Insecta: Coleoptera: Carabidae). AB - The antimicrobial properties of the pygidial gland secretions released by the adults of the three ground beetle species, Carabus ullrichii, C. coriaceus, and Abax parallelepipedus, have been tested. Microdilution method was applied for detection of minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), and minimal fungicidal concentrations (MFCs). Additionally, morpho-histology of the pygidial glands is investigated. We have tested 16 laboratory and clinical strains of human pathogens--eight bacterial both gram-positive and gram-negative species and eight fungal species. The pygidial secretion samples of C. ullrichii have showed the strongest antimicrobial effect against all strains of treated bacteria and fungi. Staphylococcus aureus, Lysteria monocytogenes, and Salmonella typhimurium proved to be the most sensitive bacterial strains. Penicillium funiculosum proved to be the most sensitive micromycete, while P. ochrochloron and P. verrucosum var. cyclopium the most resistant micromycetes. The pygidial secretion of C. coriaceus has showed antibacterial potential solely against Pseudomonas aeruginosa and antifungal activity against Aspergillus fumigatus, A. versicolor, A. ochraceus, and P. ochrochloron. Antibacterial properties of pygidial gland secretion of A. parallelepipedus were achieved against P. aeruginosa, while antifungal activity was detected against five of the eight tested micromycetes (A. fumigatus, A. versicolor, A. ochraceus, Trichoderma viride, and P. verrucosum var. cyclopium). Commercial antibiotics Streptomycin and Ampicillin and mycotics Ketoconazole and Bifonazole, applied as the positive controls, showed higher antibacterial/antifungal properties for all bacterial and fungal strains. The results of this observation might have a significant impact on the environmental aspects and possible medical purpose in the future. PMID- 27000262 TI - Antidiabetic effect of enterolactone in cultured muscle cells and in type 2 diabetic model db/db mice. AB - Enterolactone (ENL) is formed by the conversion of dietary precursors like strawberry lignans via the gut microbiota. Urinary concentrations of lignan metabolites are reported to be significantly associated with a lower risk of Type 2 diabetes (T2D). In the present study, antidiabetic effect of ENL and its modes of action were studied in vitro and in vivo employing a rat skeletal muscle derived cell line, L6 myocytes in culture, and T2D model db/db mice. ENL dose dependently increased glucose uptake in L6 myotubes under insulin absent condition. This increase by ENL was canceled by compound C, an inhibitor of 5' adenosine monophosphate-activated protein kinase (APMK). Activation (=phosphorylation) of AMPK and translocation of glucose transporter 4 (GLUT4) to plasma membrane in L6 myotubes were demonstrated by Western blotting analyses. Promotion by ENL of GLUT4 translocation to plasma membrane was also visually demonstrated by immunocytochemistry in L6 myoblasts that were transfected with glut4 cDNA-coding vector. T2D model db/db mice were fed the basal 20 % casein diet (20C) or 20C supplemented with ENL (0.001 or 0.01 %) for 6 weeks. Fasting blood glucose (FBG) levels were measured every week and intraperitoneal glucose tolerance test (IPGTT) was conducted. ENL at a higher dose (0.01 % in 20C) suppressed the increases in FBG levels. ENL was also demonstrated to improve the index of insulin resistance (HOMA-IR) and glucose intolerance by IPGTT in db/db mice. From these results, ENL is suggested to be an antidiabetic chemical entity converted from dietary lignans by gut microbiota. PMID- 27000263 TI - Development of a tree shrew metabolic syndrome model and use of umbilical cord mesenchymal stem cell transplantation for treatment. AB - The aim of this study was to establish a tree shrew metabolic syndrome model and demonstrate the utility of MSCs in treating metabolic syndrome. We used tree shrew umbilical cord mesenchymal stem cell (TS-UC-MSC) transplantation for the treatment of metabolic syndrome to demonstrate the clinical application of these stem cells and to provide a theoretical basis and reference methods for this treatment. Tree shrew metabolic syndrome model showed significant insulin resistance, high blood sugar, lipid metabolism disorders, and hypertension, consistent with the diagnostic criteria. TS-UC-MSC transplantation at 16 weeks significantly reduced blood sugar and lipid levels, improved insulin resistance and the regulation of insulin secretion, and reduced the expression levels of the pro-inflammatory cytokines IL-1 and IL-6 (P < 0.05). The transplanted TS-UC-MSCs targeted the liver, kidney and pancreas; reduced liver cell degeneration, necrosis, and inflammatory exudation; mitigated bleeding congestion and inflammatory cell infiltration in the kidney; and reduced islet cell degeneration and necrosis. We successfully developed a tree shrew metabolic syndrome model and showed that MSC migrate in diseased organs and can attenuate metabolic syndrome severity in a tree shrew model. PMID- 27000264 TI - Trends in survival of chronic lymphocytic leukemia patients in Germany and the USA in the first decade of the twenty-first century. AB - BACKGROUND: Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997-2011. METHODS: Data were extracted from 12 cancer registries in Germany and compared to the data from the USA. Period analysis was used to estimate 5- and 10-year relative survival (RS). RESULTS: Five- and 10-year RS estimates in 2009-2011 of 80.2 and 59.5%, respectively, in Germany and 82.4 and 64.7%, respectively, in the USA were observed. Overall, 5-year RS increased significantly in Germany and the difference compared to the survival in the USA which slightly decreased between 2003-2005 and 2009-2011. However, age-specific analyses showed persistently higher survival for all ages except for 15-44 in the USA. In general, survival decreased with age, but the age-related disparity was small for patients younger than 75. In both countries, 5-year RS was >80% for patients less than 75 years of age but <70% for those age 75+. CONCLUSIONS: Overall, 5-year survival for patients with CLL is good, but 10-year survival is significantly lower, and survival was much lower for those age 75+. Major differences in survival between countries were not observed. Further research into ways to increase survival for older CLL patients are needed to reduce the persistent large age-related survival disparity. PMID- 27000265 TI - The Role of Psychopathic Traits in the Development of the Therapeutic Alliance Among Sexual Offenders. AB - There is a growing body of research demonstrating that the therapeutic alliance (TA) affects outcomes among specialized forensic populations, including sexual offenders. Despite this consensus, researchers continue to question whether higher levels of psychopathic traits are conducive to the formation of a therapeutic relationship for high-risk sexual offenders. Thus, the current study adds to the literature by examining the relationship between the TA and levels of psychopathy among a sample of incarcerated sexual offenders participating in sexual offender treatment. Overall, we found no significant relationships between Psychopathy Checklist-Revised (PCL-R) scores and the Working Alliance Inventory (WAI) for either client or therapist ratings. However, when we excluded those offenders who were participating in aftercare, a significant negative relationship was found between client ratings of the Bonds subscale and PCL-R total scores. Next, after controlling for risk and group status (aftercare/non aftercare), we found no significant differences between either client or therapist total WAI scores when compared by level of psychopathy as measured by the PCL-R (low, >20; moderate, 20-30; and high, >30). Furthermore, when Factor 1 and Factor 2 scores of the PCL-R were examined individually, neither factor significantly predicted either client or therapist total WAI score after controlling for risk and group status. Findings are discussed as they pertain to the treatment of sexual offenders with elevated levels of psychopathic traits. PMID- 27000266 TI - An Evaluation of a Community-Based Psycho-Educational Program for Users of Child Sexual Exploitation Material. AB - Online sexual offenders represent an increasingly large proportion of all sexual offenders. Many of these offenders receive noncustodial sentences, and there is a growing need for community-based interventions. The aim of this study was to evaluate a psycho-educational program for community dwelling users of child sexual exploitation material (CSEM). A total of 92 adult male participants completed self-report measures at pre and post. A subset of participants also completed measures after a follow-up period. Results suggested benefits across depression, anxiety, and stress; social competency, including locus of control and self-esteem; and distorted attitudes. Furthermore, these effects remained 8 to 12 weeks following program completion. Our results suggest that CSEM users are amenable to treatment in the community and that there are beneficial outcomes in affective and interpersonal functioning following psycho-education. These factors represent treatment targets for sexual offenders and are recognized risk factors for contact sexual offense recidivism. PMID- 27000267 TI - Do Sex Offenders Have Higher Levels of Testosterone? Results From a Meta Analysis. AB - The purpose of the current study is to review the available scientific evidence on the relationship between testosterone and sexual aggression. A systematic search for all primary studies comparing basal testosterone levels in sex offenders and non-sex offenders was undertaken across 20 electronic databases using an explicit search strategy and inclusion/exclusion criteria. A total of seven studies were identified and 11 effect sizes were computed; effects were pooled using both fixed and random effects meta-analysis models. Although individual study findings present a mix of results wherein sex offenders have higher or lower baseline levels of testosterone than non-sex offenders, pooled results indicate no overall difference between groups. Moderators of the analyses suggest possibly lower rates of testosterone in child molesters than controls; however, results are dependent on study weighting. Limitations, policy implications with respect to chemical castration laws, and future directions for research are discussed. PMID- 27000268 TI - Lithium and suicide prevention in bipolar disorder. AB - INTRODUCTION: Bipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations. METHODS: We conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: "lithium" AND "suicide" OR "suicidality" OR "suicide attempt". RESULTS: As confirmed by a recent meta analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The "impulsive-aggressive" endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3alpha/beta (GSK3alpha and beta; proteins inhibited by Li) seem to be associated with more impulsiveness in BD populations. CONCLUSION: The anti-suicidal effect of Li has been very well demonstrated. By its specific action on the serotoninergic system, treatment with Li significantly reduces "impulsive aggressive" behaviour which is a vulnerability factor common to suicide and BD. Long-term appropriately modulated treatment with Li seems to have considerable impact on the reduction of suicidal behaviours, suicidal ideation and death by suicide in the BD population. PMID- 27000269 TI - The macular function and structure in patients with diabetic macular edema before and after ranibizumab treatment. AB - PURPOSE: To evaluate macular function and structure in patients with diabetic macular edema prior to, as well as 3 and 6 months after intravitreal ranibizumab treatment. PATIENTS AND METHODS: Seventeen eyes of 17 patients with type 2 diabetes mellitus and diabetic macular edema (DME) were treated with intravitreal injections of 0.5 mg ranibizumab. Prior to the first injection, as well as after 3 and 6 months, the following examinations were performed: assessment of distance best-corrected visual acuity (log MAR), perception of metamorphopsia (M-Chart), slit lamp examination of the anterior and posterior segment of the eye (Volk 90D lens), evaluation of the retinal and choroidal circulation (fluorescein angiography), assessment of the structure and thickness of the macula (OCT), as well as evaluation of the macular function (PERG and mfERG). RESULTS: We observed that ranibizumab significantly improved visual acuity after 3 and 6 months from the beginning of the treatment, which was a consequence of reduced macular edema and vascular leakage. There was a statistically significant decrease in metamorphopsia frequency at month 3; however, at month 6 it was a statistically insignificant when compared to the baseline. The results of electrophysiological examinations revealed no improvement in ranibizumab-treated patients. CONCLUSION: Improvement of visual acuity and reduction in macular thickness were maintained up to the 6-month follow-up. The results of electrophysiological examinations revealed that ranibizumab injections tend to stabilize bioelectrical macular function of the outer, middle and inner retinal layers, which was impossible to recognize on the basis of visual acuity and OCT. Therefore, the electrophysiological examinations should be used as an additional objective tool for the evaluation of the anti-VEGF treatment effectiveness in DME. PMID- 27000270 TI - [Earlier value assessment of pharmaceutical products and medical science]. PMID- 27000271 TI - Subpopulation Treatment Effect Pattern Plot (STEPP) analysis of Ki67 assay according to histology: prognostic relevance for resected early stage 'pure' and 'mixed' lobular breast cancer. AB - BACKGROUND: The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery. METHODS: Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between 'pure' or 'mixed' histology ILC and Ki67. RESULTS: At a median follow-up of 67 months, 10 years DFS and OS of 405 patients were 67.8 and 79.8%, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21%); 10-years DFS and OS were 75.1, 66.5, and 30.2% (p = 0.01) and 84.3, 76.4 and 59% (p = 0.003), for patients with a Ki67 < 6%, between 6 and 21%, and >21%, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85%, OS 100%). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with 'pure' ILC performed worse than 'mixed' histology. CONCLUSIONS: Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with 'pure' ILC. PMID- 27000272 TI - Assessment of the knowledge and perception of support of patients with heart failure SOPICA study IN SPAIN. AB - OBJECTIVE: To understand the perceptions of patients with heart failure (HF) concerning their disease, treatment and support, as well as the specialists who provide care after a decompensation, and to determine whether there is a relationship between the type of specialist involved in the follow-up and the medium-term prognosis. METHODS: A multicentre, prospective cohort study consecutively included patients with acute HF in the emergency department. The patients were interviewed by telephone 91-180days after their emergency department visit. We investigated the relationship between the type of specialist who performed the follow-up and the emergency department visits or hospitalisations using Cox regression models, with progressive adjustment by groups of potential confounders of these relationships. RESULTS: We interviewed 785 patients. Thirty-three percent (95%CI: 30%-36%) considered their disease mild, 64% (60%-67%) required help from third parties for daily activities, 65% (61%-68%) had no recent therapeutic changes, and 69% (67%-72%) received the same treatment in the exacerbations. The perceived support varied significantly depending on the factor under consideration (from greater to lesser: family, hospital, emergency department, health centre, religion and patient associations; p<.05 in all comparisons). Thirty-nine percent (36%-43%) of the patients with decompensations consulted directly with the emergency department, with no prior changes in treatment. At discharge, general practitioners (74%, 71%-77%) and cardiologists (74%, 70%-77%) were the most involved in the follow-up, although the specialty was not related to the prognosis. CONCLUSION: There are various aspects of the perception of patients with HF concerning their disease that are susceptible to future interventions. Patient follow-up involves various specialties, but all achieve similar results in the medium term. PMID- 27000273 TI - Quantification of Lipoteichoic Acid Contents and Cultivable Bacteria at the Different Phases of the Endodontic Retreatment. AB - INTRODUCTION: The infectious content of root canals, including bacteria and lipoteichoic acid (LTA), cause injuries to the periapical tissues. The purpose of this clinical study was to quantify the levels of both LTA and cultivable bacteria at the different phases of endodontic retreatment (ER) of teeth with post-treatment apical periodontitis. It also aimed to investigate the presence of gram-positive microorganisms before and after chemomechanical preparation (CMP) and intracanal medication (ICM). METHODS: Twenty infected root canals of single rooted teeth were randomly assigned into 2 groups according to the chemical substance used for CMP (n = 10 per group): chlorhexidine (CHX) group, 2% CHX gel, and the sodium hypochlorite (NaOCl) group, 6% NaOCl. Root canal samples were taken using paper points before (S1) and after CMP (S2) and after 30 days of ICM with calcium hydroxide + 2% CHX gel (S3). Microorganisms were identified by the culture technique using biochemical tests. Cultivable bacteria were determined by counting the colony-forming unit. LTA levels were measured using the enzyme linked immunosorbent assay (pg/mL). RESULTS: A total of 70 gram-positive species, out of 102 species isolated, were found in the root canals (54 in S1, 4 in S2, and 12 in S3). Enterococcus faecalis was the most frequent isolated taxon in all phases of the ER. LTA (574.0 +/- 94.7) and cultivable bacteria (101.2 +/- 79.2) were present in all S1 samples. CMP decreased the overall levels of cultivable bacteria by 99.4% and LTA by 24.8% (P < .05), whereas the total overall reduction level of ICM on viable bacteria was 99.5% and on LTA it was 38.6% (P < .05). CMP with 2% CHX gel (CHX group, 99.3%) was more effective (P < .05) than 6% NaOCl (NaOCl group, 92.1%) on bacterial reduction. Likewise, ICM showed a 100% reduction in the CHX group and 98.5% in the NaOCl group. Regarding the reduction of LTA, CMP with 2% CHX gel (CHX group, 26.9%) was more effective (P < .05) than 6% NaOCl (NaOCl group, 22.6%). In addition, ICM showed a 43.2% reduction in the CHX group and 36.2% in the NaOCl group (P > .05). CONCLUSIONS: The reduction rates of bacteria were higher than the LTA. Moreover, gram-positive microorganisms were present in all phases of the endodontic retreatment. PMID- 27000274 TI - Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors. AB - Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC. PMID- 27000275 TI - [Pancreatic lesions]. PMID- 27000277 TI - Medical Emergency Team: How do we play when we stay? Characterization of MET actions at the scene. AB - BACKGROUND: The creation, implementation and effectiveness of a medical emergency team (MET) in every hospital is encourage and supported by international bodies of quality certification. Issues such as what is the best composition of the team or the interventions performed by the MET at the scene and the immediate outcomes of the patients after MET intervention have not yet been sufficiently explored. The purpose of the study is to characterize MET actions at the scene and the immediate patient outcome. METHODS: Retrospective cohort study, at a tertiary care, university-affiliated, 600-bed hospital, in the north of Portugal, over two years. RESULTS: There were 511 MET activations: 389 (76%) were for inpatients. MET activation rate was 8.6/1,000 inpatients. The main criteria for activation were airway threatening in 143 (36.8%), concern of medical staff in 121 (31.1%) and decrease in GCS > 2 in 98 (25.2%) patients; MET calls for cardiac arrest occurred in 68 patients (17.5%). The median (IQR) time the team stayed at the scene was 35 (20-50) minutes. At the scene, the most frequent actions were related to airway and ventilation, namely oxygen administration in 145 (37.3%); in circulation, fluid were administered in 158 (40.6%); overall medication was administered in 185 (47.5%) patients. End-of-life decisions were part of the MET actions in 94 (24.1%) patients. At the end of MET intervention, 73 (18.7%) patients died at the scene, 190 (60.7%) stayed on the ward and the remaining 123 patients were transferred to an increased level of care. Crude hospital mortality rate was 4.1% in the 3 years previously to MET implementation and 3.6% in the following 3 years (p < 0.001). DISCUSSION: During the study period, the rate of activation for medical inpatients was significantly higher than that for surgical inpatients. In our hospital, there is no 24/7 medical cover on the wards, with the exception of high-dependency and intensive care units; assuming that the number of unplanned admissions and chronic ill patients is greater in medical wards that could explain the difference found, which prompts the implementation of a 24/7 ward residence. The team stayed on site for half an hour and during that time most of the actions were simple and nurse-driven, but in one third of all activations medical actions were taken, and in a forth (24%) end-of-life decisions made, reinforcing the inclusion of a doctor in the MET. A significant decrease in overall hospital mortality rate was observed after the implementation of the MET. CONCLUSIONS: The composition of our MET with an ICU doctor and nurse was reinforced by the need of medical actions in more than half of the situations (either clinical actions or end-of-life decisions). After MET implementation there was a significant decrease in hospital mortality. This study reinforces the benefit of implementing an ICU-MET team. PMID- 27000276 TI - [Ductal adenocarcinoma and unusual differential diagnosis]. AB - Ductal pancreatic adenocarcinoma is by far the most common solid tumor of the pancreas. It has a very poor prognosis, especially in the more advanced stages which are no longer locally confined. Due to mostly unspecific symptoms, imaging is key in the diagnostic process. Because of the widespread use of imaging techniques, incidental findings are to a greater extent discovered in the pancreas, which subsequently entail further work-up. Ductal pancreatic adenocarcinoma can be mimicked by a large number of different lesions, such as anatomical variants, peripancreatic structures and tumors, rarer primary solid pancreatic tumors, cystic tumors, metastases or different variants of pancreatitis. Additionally, a number of precursor lesions can be differentiated. The correct classification is thus important as an early diagnosis of ductal pancreatic adenocarcinoma is relevant for the prognosis and because the possibly avoidable treatment is very invasive. All major imaging techniques are principally suitable for pancreatic imaging. In addition to sonography of the abdomen, usually the baseline diagnostic tool, computed tomography (CT) with its superior spatial resolution, magnetic resonance imaging (MRI) with its good soft tissue differentiation capabilities, possibly in combination with MR cholangiopancreatography (MRCP), endosonography with its extraordinary spatial resolution, conceivably with additional endoscopic retrograde CP or the option of direct biopsy and finally positron emission tomography CT (PET-CT) as a molecular imaging tool are all particularly useful modalities. The various techniques all have its advantages and disadvantages; depending on the individual situation they may need to be combined. PMID- 27000278 TI - Breast cancer patient with everolimus-induced angioedema: A rare occurrence with potential for serious consequences. AB - Background The development of angioedema is a rare yet serious clinical event that may develop due to an adverse drug reaction. Rapid recognition and treatment of this adverse reaction is critical for optimal patient outcomes; however, prevention of this occurrence is preferred. Case report A 59-year-old woman presented to the emergency department with lingual angioedema caused by the addition of everolimus to her medication regimen. The patient improved after withdrawal of the offending agent and standard treatment. Early recognition by healthcare providers and management of everolimus-induced angioedema is vital for successful patient outcomes. This report increases awareness of everolimus as a potentially causative agent for the development of angioedema. PMID- 27000279 TI - Cost avoidance from dose rounding biologic and cytotoxic antineoplastics. AB - Background To reduce product wastage, our institution allows automatic dose rounding of biologic and cytotoxic anticancer agents. The purpose of this project was to determine the actual annual cost avoidance due to pharmacist-managed automatic dose rounding of anticancer treatments. Methods Financial impact was assessed within the context of our departmental standard work which supports automatic dose rounding of biologic anticancer agents (+/-10%) and cytotoxic anticancer agents (+/-5%) to the nearest vial size for body surface area- or weight-based doses. Exclusions to automatic dose rounding include multiple dose vial products, pediatric orders, clinical trial drugs, and parenteral busulfan. The amount of cost avoidance for each rounded dose was determined using the product acquisition cost of the smallest available product amount. Data were collected from anticancer treatment orders for the fiscal year 1 July 2013 to 30 June 2014. Results A total of 6216 doses of anticancer drugs were checked for dose rounding during the period of data collection. Almost $200,000 in product acquisition cost was avoided with pharmacist-managed automatic dose rounding. Six different biologic products accounted for approximately 7% of the total doses analyzed and 78% of the cost avoidance. Fifteen drugs comprised the array of cytotoxic agents rounded. Approximately, 37% and 4% of the biologic and cytotoxic doses were rounded up to the vial size. Conclusion Routine dose rounding of biologic anticancer agents (+/-10%) and cytotoxic products (+/-5%) achieved cost avoidance through reduction of drug wastage at our institution. PMID- 27000280 TI - Mixed outpatient-inpatient autologous stem cell transplant for multiple myeloma: A cost-saving initiative in a resource constrained environment. AB - Background Although administration of chemotherapy prior to autologous stem cell transplantation in the outpatient setting has been reported as safe and cost effective, many limitations exist with previously reported methods of transitioning out of the hospital ward. Specifically, lack of a caregiver and distance from treatment facility are key factors particularly in rural settings. Given these limitations, not all institutions have transitioned the transplant process, or even portions of it, to the outpatient setting despite the known benefits. Methods To achieve financial benefit without compromising safety, a novel mixed outpatient-inpatient model was adopted at our institution. Eligible patients receive melphalan in the clinic the day prior to being admitted for peripheral blood stem cell re-infusion where they remain until recovery of myelosuppression. Results In the year since implementation, nineteen total patients received high-dose melphalan prior to autologous stem cell transplantation. Eighteen of these patients successfully received melphalan in the outpatient clinic with admission to the hospital on day zero for infusion of stem cells. No patient experienced any adverse event on the day or evening of chemotherapy or required early admission. The average estimated total reduction in cost per patient to the institution was over US$2,000. When comparing the cost of the chemotherapy drug, melphalan, from the year before and the year after implementation of the mixed model the total annual cost saving was approximately US$90,00 or 53% of the previous year's expenditure. Conclusions The implementation of this mixed outpatient-inpatient model was safe, feasible, and cost-effective. PMID- 27000281 TI - [A banal history of exemplary treatment]. PMID- 27000282 TI - Estimating the DNA strand breakage using a fuzzy inference system and agarose gel electrophoresis, a case study with toothed carp Aphanius sophiae exposed to cypermethrin. AB - The DNA breakage has been widely used in ecotoxicological studies to investigate effects of pesticides in fishes. The present study used a fuzzy inference system to quantify the breakage of DNA double strand in Aphanius sophiae exposed to the cypermethrin. The specimens were adapted to different temperatures and salinity for 14 days and then exposed to cypermethrin. DNA of each specimens were extracted, electrophoresed and photographed. A fuzzy system with three input variables and 27 rules were defined. The pixel value curve of DNA on each gel lane was obtained using ImageJ. The DNA breakage was quantified using the pixel value curve and fuzzy system. The defuzzified values were analyzed using a three way analysis of variance. Cypermethrin had significant effects on DNA breakage. Fuzzy inference systems can be used as a tool to quantify the breakage of double strand DNA. DNA double strand of the gill of A. sophiae is sensitive enough to be used to detect cypermethrin in surface waters in concentrations much lower than those reported in previous studies. PMID- 27000283 TI - [A study of non-muscle-invasive bladder cancer therapy : Treatment of high-grade non-muscle-invasive urothelial carcinoma of the bladder with the standard number and dosage of intravesical BCG instillations versus a reduced number intravesical BCG instillations at the standard dosage: A European Association of Urology Research Foundation randomized phase 3 study - NIMBUS - AB 37/10 of the AUO]. PMID- 27000284 TI - [Scientific activity of the University Urological Department in Budapest after WWII (1946-1956)]. AB - The authors studied the publications written by the staff of the University Department of Urology in Budapest, Hungary between 1946 and 1956. The collection was contributed on the occasion of Professor Babics's 10-year-long chairmanship. Over a period of 10 years, 214 papers were published by 15 urologists, including 3 books and 3 PhD theses; 16 papers were published in German, 22 in English, 2 in French, and 1 in Italian. The most frequent topic of the papers (26) was basic science (e.g., ureter motility, lymph circulation, intrarenal pressure condition). Other papers dealt with nephrology, artificial kidneys, TURP, and nephron-sparing renal surgery. Some articles examined various types of malignant tumors and benign prostatic hyperplasia, while 17 publications focused on the topic of andrology. Tuberculosis was also discussed by the authors. Despite political isolation, the communist dictatorship, poverty, the lack of health equipment, physicians educated before WWII with their work morality and hard work managed to perform contemporary clinical and basic scientific research. PMID- 27000285 TI - Temporal mammogram image registration using optimized curvilinear coordinates. AB - Registration of mammograms plays an important role in breast cancer computer aided diagnosis systems. Radiologists usually compare mammogram images in order to detect abnormalities. The comparison of mammograms requires a registration between them. A temporal mammogram registration method is proposed in this paper. It is based on the curvilinear coordinates, which are utilized to cope both with global and local deformations in the breast area. Temporal mammogram pairs are used to validate the proposed method. After registration, the similarity between the mammograms is maximized, and the distance between manually defined landmarks is decreased. In addition, a thorough comparison with the state-of-the-art mammogram registration methods is performed to show its effectiveness. PMID- 27000286 TI - Using numeric simulation in an online e-learning environment to teach functional physiological contexts. AB - BACKGROUND AND OBJECTIVES: Mathematical models are suitable to simulate complex biological processes by a set of non-linear differential equations. These simulation models can be used as an e-learning tool in medical education. However, in many cases these mathematical systems have to be treated numerically which is computationally intensive. The aim of the study was to develop a system for numerical simulation to be used in an online e-learning environment. METHODS: In the software system the simulation is located on the server as a CGI application. The user (student) selects the boundary conditions for the simulation (e.g., properties of a simulated patient) on the browser. With these parameters the simulation on the server is started and the simulation result is re-transferred to the browser. RESULTS: With this system two examples of e learning units were realized. The first one uses a multi-compartment model of the glucose-insulin control loop for the simulation of the plasma glucose level after a simulated meal or during diabetes (including treatment by subcutaneous insulin application). The second one simulates the ion transport leading to the resting and action potential in nerves. The student can vary parameters systematically to explore the biological behavior of the system. CONCLUSIONS: The described system is able to simulate complex biological processes and offers the possibility to use these models in an online e-learning environment. As far as the underlying principles can be described mathematically, this type of system can be applied to a broad spectrum of biomedical or natural scientific topics. PMID- 27000287 TI - Quality optimized medical image information hiding algorithm that employs edge detection and data coding. AB - OBJECTIVES: The present work has the goal of developing a secure medical imaging information system based on a combined steganography and cryptography technique. It attempts to securely embed patient's confidential information into his/her medical images. METHODS: The proposed information security scheme conceals coded Electronic Patient Records (EPRs) into medical images in order to protect the EPRs' confidentiality without affecting the image quality and particularly the Region of Interest (ROI), which is essential for diagnosis. The secret EPR data is converted into ciphertext using private symmetric encryption method. Since the Human Visual System (HVS) is less sensitive to alterations in sharp regions compared to uniform regions, a simple edge detection method has been introduced to identify and embed in edge pixels, which will lead to an improved stego image quality. In order to increase the embedding capacity, the algorithm embeds variable number of bits (up to 3) in edge pixels based on the strength of edges. Moreover, to increase the efficiency, two message coding mechanisms have been utilized to enhance the +/-1 steganography. The first one, which is based on Hamming code, is simple and fast, while the other which is known as the Syndrome Trellis Code (STC), is more sophisticated as it attempts to find a stego image that is close to the cover image through minimizing the embedding impact. The proposed steganography algorithm embeds the secret data bits into the Region of Non Interest (RONI), where due to its importance; the ROI is preserved from modifications. RESULTS: The experimental results demonstrate that the proposed method can embed large amount of secret data without leaving a noticeable distortion in the output image. The effectiveness of the proposed algorithm is also proven using one of the efficient steganalysis techniques. CONCLUSION: The proposed medical imaging information system proved to be capable of concealing EPR data and producing imperceptible stego images with minimal embedding distortions compared to other existing methods. In order to refrain from introducing any modifications to the ROI, the proposed system only utilizes the Region of Non Interest (RONI) in embedding the EPR data. PMID- 27000288 TI - Cancer-disease associations: A visualization and animation through medical big data. AB - OBJECTIVE: Cancer is the primary disease responsible for death and disability worldwide. Currently, prevention and early detection represents the best hope for cure. Knowing the expected diseases that occur with a particular cancer in advance could lead to physicians being able to better tailor their treatment for cancer. The aim of this study was to build an animated visualization tool called as Cancer Associations Map Animation (CAMA), to chart the association of cancers with other disease over time. METHODS: The study population was collected from the Taiwan National Health Insurance Database during the period January 2000 to December 2002, 782 million outpatient visits were used to compute the associations of nine major cancers with other diseases. A motion chart was used to quantify and visualize the associations between diseases and cancers. RESULTS: The CAMA motion chart that was built successfully facilitated the observation of cancer-disease associations across ages and genders. The CAMA system can be accessed online at http://203.71.86.98/web/runq16.html. CONCLUSION: The CAMA animation system is an animated medical data visualization tool which provides a dynamic, time-lapse, animated view of cancer-disease associations across different age groups and gender. Derived from a large, nationwide healthcare dataset, this exploratory data analysis tool can detect cancer comorbidities earlier than is possible by manual inspection. Taking into account the trajectory of cancer-specific comorbidity development may facilitate clinicians and healthcare researchers to more efficiently explore early stage hypotheses, develop new cancer treatment approaches, and identify potential effect modifiers or new risk factors associated with specific cancers. PMID- 27000289 TI - Arrhythmia recognition and classification using combined linear and nonlinear features of ECG signals. AB - Arrhythmia is a cardiac condition caused by abnormal electrical activity of the heart, and an electrocardiogram (ECG) is the non-invasive method used to detect arrhythmias or heart abnormalities. Due to the presence of noise, the non stationary nature of the ECG signal (i.e. the changing morphology of the ECG signal with respect to time) and the irregularity of the heartbeat, physicians face difficulties in the diagnosis of arrhythmias. The computer-aided analysis of ECG results assists physicians to detect cardiovascular diseases. The development of many existing arrhythmia systems has depended on the findings from linear experiments on ECG data which achieve high performance on noise-free data. However, nonlinear experiments characterize the ECG signal more effectively sense, extract hidden information in the ECG signal, and achieve good performance under noisy conditions. This paper investigates the representation ability of linear and nonlinear features and proposes a combination of such features in order to improve the classification of ECG data. In this study, five types of beat classes of arrhythmia as recommended by the Association for Advancement of Medical Instrumentation are analyzed: non-ectopic beats (N), supra-ventricular ectopic beats (S), ventricular ectopic beats (V), fusion beats (F) and unclassifiable and paced beats (U). The characterization ability of nonlinear features such as high order statistics and cumulants and nonlinear feature reduction methods such as independent component analysis are combined with linear features, namely, the principal component analysis of discrete wavelet transform coefficients. The features are tested for their ability to differentiate different classes of data using different classifiers, namely, the support vector machine and neural network methods with tenfold cross-validation. Our proposed method is able to classify the N, S, V, F and U arrhythmia classes with high accuracy (98.91%) using a combined support vector machine and radial basis function method. PMID- 27000290 TI - Classification of THz pulse signals using two-dimensional cross-correlation feature extraction and non-linear classifiers. AB - This work provides a performance comparison of four different machine learning classifiers: multinomial logistic regression with ridge estimators (MLR) classifier, k-nearest neighbours (KNN), support vector machine (SVM) and naive Bayes (NB) as applied to terahertz (THz) transient time domain sequences associated with pixelated images of different powder samples. The six substances considered, although have similar optical properties, their complex insertion loss at the THz part of the spectrum is significantly different because of differences in both their frequency dependent THz extinction coefficient as well as differences in their refractive index and scattering properties. As scattering can be unquantifiable in many spectroscopic experiments, classification solely on differences in complex insertion loss can be inconclusive. The problem is addressed using two-dimensional (2-D) cross-correlations between background and sample interferograms, these ensure good noise suppression of the datasets and provide a range of statistical features that are subsequently used as inputs to the above classifiers. A cross-validation procedure is adopted to assess the performance of the classifiers. Firstly the measurements related to samples that had thicknesses of 2mm were classified, then samples at thicknesses of 4mm, and after that 3mm were classified and the success rate and consistency of each classifier was recorded. In addition, mixtures having thicknesses of 2 and 4mm as well as mixtures of 2, 3 and 4mm were presented simultaneously to all classifiers. This approach provided further cross-validation of the classification consistency of each algorithm. The results confirm the superiority in classification accuracy and robustness of the MLR (least accuracy 88.24%) and KNN (least accuracy 90.19%) algorithms which consistently outperformed the SVM (least accuracy 74.51%) and NB (least accuracy 56.86%) classifiers for the same number of feature vectors across all studies. The work establishes a general methodology for assessing the performance of other hyperspectral dataset classifiers on the basis of 2-D cross-correlations in far-infrared spectroscopy or other parts of the electromagnetic spectrum. It also advances the wider proliferation of automated THz imaging systems across new application areas e.g., biomedical imaging, industrial processing and quality control where interpretation of hyperspectral images is still under development. PMID- 27000291 TI - A diagnostic tool for population models using non-compartmental analysis: The ncappc package for R. AB - BACKGROUND AND OBJECTIVE: Non-compartmental analysis (NCA) calculates pharmacokinetic (PK) metrics related to the systemic exposure to a drug following administration, e.g. area under the concentration-time curve and peak concentration. We developed a new package in R, called ncappc, to perform (i) a NCA and (ii) simulation-based posterior predictive checks (ppc) for a population PK (PopPK) model using NCA metrics. METHODS: The nca feature of ncappc package estimates the NCA metrics by NCA. The ppc feature of ncappc estimates the NCA metrics from multiple sets of simulated concentration-time data and compares them with those estimated from the observed data. The diagnostic analysis is performed at the population as well as the individual level. The distribution of the simulated population means of each NCA metric is compared with the corresponding observed population mean. The individual level comparison is performed based on the deviation of the mean of any NCA metric based on simulations for an individual from the corresponding NCA metric obtained from the observed data. The ncappc package also reports the normalized prediction distribution error (NPDE) of the simulated NCA metrics for each individual and their distribution within a population. RESULTS: The ncappc produces two default outputs depending on the type of analysis performed, i.e., NCA and PopPK diagnosis. The PopPK diagnosis feature of ncappc produces 8 sets of graphical outputs to assess the ability of a population model to simulate the concentration-time profile of a drug and thereby evaluate model adequacy. In addition, tabular outputs are generated showing the values of the NCA metrics estimated from the observed and the simulated data, along with the deviation, NPDE, regression parameters used to estimate the elimination rate constant and the related population statistics. CONCLUSIONS: The ncappc package is a versatile and flexible tool-set written in R that successfully estimates NCA metrics from concentration-time data and produces a comprehensive set of graphical and tabular output to summarize the diagnostic results including the model specific outliers. The output is easy to interpret and to use in evaluation of a population PK model. ncappc is freely available on CRAN (http://cran.r-project.org/web/packages/ncappc/index.html/) and GitHub (https://github.com/cacha0227/ncappc/). PMID- 27000292 TI - Feature selection and classification methodology for the detection of knee-joint disorders. AB - Vibroarthographic (VAG) signals emitted from the knee joint disorder provides an early diagnostic tool. The nonstationary and nonlinear nature of VAG signal makes an important aspect for feature extraction. In this work, we investigate VAG signals by proposing a wavelet based decomposition. The VAG signals are decomposed into sub-band signals of different frequencies. Nonlinear features such as recurrence quantification analysis (RQA), approximate entropy (ApEn) and sample entropy (SampEn) are extracted as features of VAG signal. A total of twenty-four features form a vector to characterize a VAG signal. Two feature selection (FS) techniques, apriori algorithm and genetic algorithm (GA) selects six and four features as the most significant features. Least square support vector machines (LS-SVM) and random forest are proposed as classifiers to evaluate the performance of FS techniques. Results indicate that the classification accuracy was more prominent with features selected from FS algorithms. Results convey that LS-SVM using the apriori algorithm gives the highest accuracy of 94.31% with false discovery rate (FDR) of 0.0892. The proposed work also provided better classification accuracy than those reported in the previous studies which gave an accuracy of 88%. This work can enhance the performance of existing technology for accurately distinguishing normal and abnormal VAG signals. And the proposed methodology could provide an effective non invasive diagnostic tool for knee joint disorders. PMID- 27000293 TI - Classification of gene expression data: A hubness-aware semi-supervised approach. AB - BACKGROUND AND OBJECTIVE: Classification of gene expression data is the common denominator of various biomedical recognition tasks. However, obtaining class labels for large training samples may be difficult or even impossible in many cases. Therefore, semi-supervised classification techniques are required as semi supervised classifiers take advantage of unlabeled data. METHODS: Gene expression data is high-dimensional which gives rise to the phenomena known under the umbrella of the curse of dimensionality, one of its recently explored aspects being the presence of hubs or hubness for short. Therefore, hubness-aware classifiers have been developed recently, such as Naive Hubness-Bayesian k Nearest Neighbor (NHBNN). In this paper, we propose a semi-supervised extension of NHBNN which follows the self-training schema. As one of the core components of self-training is the certainty score, we propose a new hubness-aware certainty score. RESULTS: We performed experiments on publicly available gene expression data. These experiments show that the proposed classifier outperforms its competitors. We investigated the impact of each of the components (classification algorithm, semi-supervised technique, hubness-aware certainty score) separately and showed that each of these components are relevant to the performance of the proposed approach. CONCLUSIONS: Our results imply that our approach may increase classification accuracy and reduce computational costs (i.e., runtime). Based on the promising results presented in the paper, we envision that hubness-aware techniques will be used in various other biomedical machine learning tasks. In order to accelerate this process, we made an implementation of hubness-aware machine learning techniques publicly available in the PyHubs software package (http://www.biointelligence.hu/pyhubs) implemented in Python, one of the most popular programming languages of data science. PMID- 27000294 TI - A real-time method to reduce ballistocardiogram artifacts from EEG during fMRI based on optimal basis sets (OBS). AB - BACKGROUND: The simultaneous acquisition of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) provides both high temporal and spatial resolution when measuring brain activity. A real-time analysis during a simultaneous EEG-fMRI acquisition is essential when studying neurofeedback and conducting effective brain activity monitoring. However, the ballistocardiogram (BCG) artifacts which are induced by heartbeat-related electrode movements in an MRI scanner severely contaminate the EEG signals and hinder a reliable real-time analysis. NEW METHOD: The optimal basis sets (OBS) method is an effective candidate for removing BCG artifacts in a traditional offline EEG-fMRI analysis, but has yet to be applied to a real-time EEG-fMRI analysis. Here, a novel real time technique based on OBS method (rtOBS) is proposed to remove BCG artifacts on a moment-to-moment basis. Real-time electrocardiogram R-peak detection procedure and sliding window OBS method were adopted. RESULTS: A series of simulated data was constructed to verify the feasibility of the rtOBS technique. Furthermore, this method was applied to real EEG-fMRI data to remove BCG artifacts. The results of both simulated data and real EEG-fMRI data from eight healthy human subjects demonstrate the effectiveness of rtOBS in both the time and frequency domains. COMPARISON WITH EXISTING METHODS: A comparison between rtOBS and real time averaged artifact subtraction (rtAAS) was conducted. The results suggest the efficacy and advantage of rtOBS in the real-time removal of BCG artifacts. CONCLUSIONS: In this study, a novel real-time OBS technique was proposed for the real-time removal of BCG artifacts. The proposed method was tested using simulated data and applied to real simultaneous EEG-fMRI data. The results suggest the effectiveness of this method. PMID- 27000295 TI - PopED lite: An optimal design software for preclinical pharmacokinetic and pharmacodynamic studies. AB - BACKGROUND AND OBJECTIVE: Optimal experimental design approaches are seldom used in preclinical drug discovery. The objective is to develop an optimal design software tool specifically designed for preclinical applications in order to increase the efficiency of drug discovery in vivo studies. METHODS: Several realistic experimental design case studies were collected and many preclinical experimental teams were consulted to determine the design goal of the software tool. The tool obtains an optimized experimental design by solving a constrained optimization problem, where each experimental design is evaluated using some function of the Fisher Information Matrix. The software was implemented in C++ using the Qt framework to assure a responsive user-software interaction through a rich graphical user interface, and at the same time, achieving the desired computational speed. In addition, a discrete global optimization algorithm was developed and implemented. RESULTS: The software design goals were simplicity, speed and intuition. Based on these design goals, we have developed the publicly available software PopED lite (http://www.bluetree.me/PopED_lite). Optimization computation was on average, over 14 test problems, 30 times faster in PopED lite compared to an already existing optimal design software tool. PopED lite is now used in real drug discovery projects and a few of these case studies are presented in this paper. CONCLUSIONS: PopED lite is designed to be simple, fast and intuitive. Simple, to give many users access to basic optimal design calculations. Fast, to fit a short design-execution cycle and allow interactive experimental design (test one design, discuss proposed design, test another design, etc). Intuitive, so that the input to and output from the software tool can easily be understood by users without knowledge of the theory of optimal design. In this way, PopED lite is highly useful in practice and complements existing tools. PMID- 27000296 TI - Social media as a primary source of medical knowledge acquisition and dissemination. PMID- 27000297 TI - Utilisation patterns and cost of hospital care for people living with HIV in Ireland in 2012: a single-centre study. AB - Data on the pattern and cost of health service use by HIV patients are required for evaluations of the cost-effectiveness of new drugs and technologies as well as being essential for service planning. The aim of this study was to identify the utilisation patterns and cost of hospital care for HIV patients in a single centre in Ireland in 2012. Data on the frequency and non-drug costs of all hospital resources used by HIV patients were extracted from a hospital activity based costing system. Cost data were analysed using a generalised linear model. A total of 328 patients, 3672 patient months, were included in this study. Patients had a mean of 4.4 scheduled infectious disease outpatient appointments per patient year; 37% of patients also used another outpatient service, 15% in patient services, 4% day-case service and 18% emergency department services in 2012. Patients with very advanced HIV disease continue to incur a disproportionate amount of the total cost of providing care. This study provides baseline utilisation and cost data for use of both infectious-disease and non infectious disease hospital services and will be useful for service planning in light of the likely increases in resource demands. PMID- 27000298 TI - High prevalence of Mycobacterium tuberculosis bacteraemia among a cohort of HIV infected patients with severe sepsis in Lusaka, Zambia. AB - Tuberculosis is recognised as one of the leading causes of severe sepsis among HIV-infected patients. Most patients with Mycobacterium tuberculosis bacteraemia have advanced HIV disease with CD4 counts less than 100 cells/MUl and its presentation is non-specific in most instances. This was a cross-sectional study which was done by analyzing data from 201 adult HIV-infected patients who met the inclusion criteria for severe sepsis. The prevalence of Mycobacterium tuberculosis bactraemia in the study population was 34.8%. Severe sepsis caused by other etiologies was observed in 33 (16.4%) of the participants. Concomitant infection of Mycobacterium tuberculosis bactraemia with other organisms is not uncommon in patients with severe sepsis. This cohort of HIV-infected patients had severe immunosuppression with a median CD4 count of 51 (20-136) cells/MUl with moderate anaemia, mean haemoglobin 8.0 (3.0) g/dl, and were generally underweight with a mean mid upper arm circumference (MUAC) of 21.0 (3.4) cm. Mycobacterium tuberculosis bacteraemia is very common in HIV-infected patients with advanced HIV disease who present with severe sepsis. Mycobacterium tuberculosis bacteraemia co-infection with aerobic organisms is not uncommon. Factors that were independently associated with Mycobacterium tuberculosis bacteraemia in our study population were MUAC and sodium level. PMID- 27000299 TI - Correlates of recent HIV testing among substance-using men who have sex with men. AB - Men who have sex with men are disproportionately impacted by HIV and substance use is a key driver of HIV risk and transmission among this population. We conducted a cross-sectional survey of 3242 HIV-negative substance-using men who have sex with men aged 18 + in the San Francisco Bay Area from March 2009 to May 2012. Demographic characteristics and sexual risk and substance use behaviors in the last six months were collected using structured telephone questionnaires. We used multivariable logistic regression to identify independent demographic and behavioral predictors of recent HIV testing. In all, 65% reported having an HIV test in the last six months. In multivariable analysis, increasing age (aOR = 0.87, 95% CI = 0.84-0.90) and drinking alcohol (<1 drink/day: 0.65, 0.46-0.92; 2 3 drinks/day: 0.64, 0.45-0.91; 4 + drinks/day: 0.52, 0.35-0.78) were negatively associated with recent HIV testing. Having two or more condomless anal intercourse partners (2.17, 1.69-2.79) was positively associated with having a recent HIV test, whereas condomless anal intercourse with serodiscordant partners was not significantly associated with testing. Older men who have sex with men and those who drink alcohol may benefit from specific targeting in efforts to expand HIV testing. Inherently riskier discordant serostatus of partners is not as significant a motivator of HIV testing as condomless anal intercourse in general. PMID- 27000300 TI - Occupational stress experienced by residents and faculty physicians on night shifts. AB - BACKGROUND: Occupational stress is an undesired factor causing discomfort for healthcare workers. Stressors in work can lead to dissatisfaction and in turn, this may affect patient care adversely. The aim of this study was to evaluate the occupational stress among residents and faculty physicians of various medical specialties working night shifts. METHODS: Residents and faculty physicians working night shifts in the emergency departments, medical and surgical wards were questioned with Swedish Demand Control Support Questionnaire. Also, various factors (specialty, marital status, sex, number of patients during a typical shift, number of night shifts per month, decision about career making in that specialty, having chronic disease and/or sleep problem) originated from social life or working conditions were investigated that could affect the demand, job control and job strain model. RESULTS: Of the 108 participants, the mean age was 31 +/- 6 years, 40.7% were female, and 78.7% were residents. Job strain was similar among the three physician groups (p > 0.05). Job control and social support was found to be lower among residents while job stress was higher. The social support-scores were lower in residents who were responsible for more than 60 patients, and who had a chronic disease. The demand-scores were lower in faculty physicians who worked 1 to 4 night shifts per month. Job strain was higher in residents with respect to faculty physicians. DISCUSSION: Stress and psychosocial risk factors are considered critical issues in the field of occupational health. Workload and job stress are stated as predictors of workers' health, productivity, and motivation. We found a few job stressors by physician working night shifts such as number of taken care of patient, having chronic disease. But, these physicians were significantly residents, due to their high workload sense. Interestingly, job stress was not more by emergency physicians than others. CONCLUSIONS: Job strain was found to be higher among the residents as compared to the faculty physicians. Job strain was not significantly different among the physicians of emergency medicine than the physicians of the other specialties working night shifts. PMID- 27000301 TI - Mothers with depressive symptoms display differential brain activations when empathizing with infant faces. AB - Maternal care during the first year of life provides the foundation for the infant's emotional and cognitive development. Depressive symptoms in mothers can undermine their early dyadic interaction, which may lead to various psychopathological disorders with long-term consequences. During this period, the mother-child interaction is exclusively preverbal and is based on the mother's ability to understand her infant's needs and feelings (i.e., empathy) and on reciprocal imitation of facial expressions that promote a social dialog that influences the development of the infant self. To study the effects of maternal depressive symptoms on neural circuits underlying these processes, we studied 16 healthy mothers (H) and 14 mothers with depressive symptoms (D), as assessed by the Center for Epidemiologic Studies Depression Scale. Subjects underwent functional magnetic resonance during observation/empathizing (OE) and imitation (IM) of the faces of both their own child and of that of an unknown child aged between 6 and 12 months. During OE, D deactivated the orbital and medial prefrontal cortex to a greater extent (compared with H), thus pointing to an increased internally focused cognitive style during rest. Moreover, D, in respect to H, displayed a greater reactivity of the right amygdala, which may be an expression of emotional dysregulation. PMID- 27000302 TI - Brain parcellation choice affects disease-related topology differences increasingly from global to local network levels. AB - Network-based analyses of deviant brain function have become extremely popular in psychiatric neuroimaging. Underpinning brain network analyses is the selection of appropriate regions of interest (ROIs). Although ROI selection is fundamental in network analysis, its impact on detecting disease effects remains unclear. We investigated the impact of parcellation choice when comparing results from different studies. We investigated the effects of anatomical (AAL) and literature based (Dosenbach) parcellation schemes on comparability of group differences in 35 female patients with anorexia nervosa and 35 age- and sex-matched healthy controls. Global and local network properties, including network-based statistics (NBS), were assessed on resting state functional magnetic resonance imaging data obtained at 3T. Parcellation schemes were comparably consistent on global network properties, while NBS and local metrics differed in location, but not metric type. Location of local metric alterations varied for AAL (parietal and cingulate cortices) versus Dosenbach (insula, thalamus) parcellation approaches. However, consistency was observed for the occipital cortex. Patient-specific global network properties can be robustly observed using different parcellation schemes, while graph metrics characterizing impairments of individual nodes vary considerably. Therefore, the impact of parcellation choice on specific group differences varies depending on the level of network organization. PMID- 27000303 TI - Disrupted amplitude of low-frequency fluctuations in antipsychotic-naive adolescents with early-onset schizophrenia. AB - Evidence points to a crucial role for altered neural oscillations and synchrony in the pathophysiology of schizophrenia. Previous resting state functional magnetic resonance imaging (fMRI) studies found aberrant amplitudes of low frequency oscillations in adult patients with schizophrenia. Whether the abnormality is also present in adolescents with early-onset schizophrenia (EOS) is largely unknown. We recruited 39 adolescents with a first episode of EOS and 31 age- and education- matched healthy controls. Resting state fMRI was obtained using an echo-planar imaging sequence. Voxel-wise amplitude of low-frequency (0.01-0.08Hz) fluctuations (ALFF) was compared between groups. We investigated seed-based functional connectivity between significantly disturbed ALFF regions and whole brain voxels in all participants. EOS participants exhibited significantly increased ALFF values in the orbitofrontal cortex (OFC) and decreased ALFF in the ventral precuneus compared with controls. Decreased ALFF values in the precuneus of EOS showed a significant negative correlation with negative symptom scores on the Positive and Negative Syndrome Scale. Disturbed functional connectivity mainly occurred between the orbitofrontal cortex and the temporal cortex in EOS. These findings demonstrate abnormal spontaneous neuronal activity and functional connectivity in the frontal and parietal cortex of EOS. Aberrant ALFF in the precuneus might be a biomarker of EOS. PMID- 27000305 TI - Combat exposure is associated with cortical thickness in Veterans with a history of chronic pain. AB - Chronic Pain (CP) has been associated with changes in gray matter integrity in the cingulate and insular cortex. However, these changes have not been studied in Veterans, despite high prevalence rates of CP and interactions with combat derived disorders. In the current study, 54 Veterans with a history of CP and 103 Veterans without CP were recruited from the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS). Cortical thickness from structural MRI scans was determined using the FreeSurfer software package. Results showed that Veterans with CP showed a negative association between cortical thickness and levels of combat exposure in the left inferior frontal gyrus and superior parietal cortex, as well as the right rostral middle frontal gyrus, precentral and postcentral gyri and the superior temporal cortex. These findings suggest that CP may alter the relationship between cortical thickness and exposure to the stress of combat. PMID- 27000304 TI - Microstructural changes to the brain of mice after methamphetamine exposure as identified with diffusion tensor imaging. AB - Methamphetamine (METH) is an addictive psychostimulant inducing neurotoxicity. Human magnetic resonance imaging and diffusion tensor imaging (DTI) of METH dependent participants find various structural abnormities. Animal studies demonstrate immunohistochemical changes in multiple cellular pathways after METH exposure. Here, we characterized the long-term effects of METH on brain microstructure in mice exposed to an escalating METH binge regimen using in vivo DTI, a methodology directly translatable across species. Results revealed four patterns of differential fractional anisotropy (FA) and mean diffusivity (MD) response when comparing METH-exposed (n=14) to saline-treated mice (n=13). Compared to the saline group, METH-exposed mice demonstrated: 1) decreased FA with no change in MD [corpus callosum (posterior forceps), internal capsule (left), thalamus (medial aspects), midbrain], 2) increased MD with no change in FA [posterior isocortical regions, caudate-putamen, hypothalamus, cerebral peduncle, internal capsule (right)], 3) increased FA with decreased MD [frontal isocortex, corpus callosum (genu)], and 4) increased FA with no change or increased MD [hippocampi, amygdala, lateral thalamus]. MD was negatively associated with calbindin-1 in hippocampi and positively with dopamine transporter in caudate-putamen. These findings highlight distributed and differential METH effects within the brain suggesting several distinct mechanisms. Such mechanisms likely change brain tissue differentially dependent upon neural location. PMID- 27000306 TI - Decreased gray matter volume is associated with the subtypes of psychotic symptoms in patients with antipsychotic-naive mild or moderate Alzheimer's disease: A voxel-based morphometry study. AB - The purpose of this study was to investigate the association between brain regional gray matter volume and two subtypes of psychotic symptoms, namely paranoid and misidentification subtypes, in antipsychotic-naive mild or moderate Alzheimer's disease (AD) patients. Forty AD patients with psychotic symptoms and 25 AD patients without psychotic symptoms were assessed for cognitive and functional impairment. Presence and subtype of psychotic symptoms were assessed by using the delusion and hallucination subscale of the Korean Neuropsychiatric Inventory (K-NPI). Structural MRI images were acquired on a 3 T scanner, and were analyzed using voxel-based morphometry (VBM) for automated analysis. The misidentification subtype is associated with more severe gray matter atrophy, and paranoid subtype is associated with less severe gray matter atrophy compared to non-psychosis group. These results suggest that the misidentification, the paranoid subtype and the non-psychosis group have a distinct neural correlation. PMID- 27000307 TI - Brain effects of computer-assisted cognitive remediation therapy in anorexia nervosa: A pilot fMRI study. AB - Poor cognitive-behavioral flexibility is considered a trait marker in anorexia nervosa (AN) that can be improved by cognitive remediation therapy (CRT). The present pilot study aimed at identifying changes in brain function potentially associated with CRT in AN. Data was obtained from a randomized, controlled trial. Twenty-four patients were assessed before and after 30 sessions of either CRT or a non-specific neurocognitive therapy. Voxel-wise analysis of whole brain functional magnetic resonance imaging was applied. Brain activation was measured during response inhibition and task switching. Although results did not reach significance, we found tentative support for CRT-related increases in brain activation in the dorsal putamen during task switching and in the dorsolateral prefrontal, sensorimotor and temporal cortex during response inhibition. These pilot findings provide viable pathways for future research on brain changes underlying CRT in AN. PMID- 27000308 TI - Altered response-preparation in patients with adult ADHD: A high-density ERP study. AB - Aberrations in early-developing bottom-up processes, such as stimulus-driven response preparation, are thought to play a critical role in the onset of ADHD, and in its persistence over time. Electrophysiology offers a unique tool to gain insight into response preparation, since response preparation has been associated with distinctive ERP changes, including negative potential-shifts which occur predominantly over frontal brain areas. We examined response-preceding negative potential shifts (RPNS) as a probe of response-preparation in adult ADHD patients by obtaining high-density event-related potentials from 33 ADHD and 29 matched healthy subjects during a Go/Nogo task using a 128-channel BioSemi recording system. Compared to controls, ADHD patients showed enhancement of the RPNS in fronto-central brain regions in the Go condition during correct responses. This change was associated with poor performance in the Stroop incongruency-task: the greater the enhancement, the higher the proportion of errors. Moreover, the ERP enhancement showed association with the severity of ADHD-symptoms; and with heightened response-variability. Thus, ADHD patients demonstrate neurophysiological alterations in response-preparation and response-preceding brain activity, suggestive of excessive activation of prefrontal neural circuits. Given the correlation with neuropsychological and psychopathological measures, these changes may constitute a pathway for core symptoms of ADHD, including premature and impaired response-preparation and motor-hyperactivity. PMID- 27000309 TI - Functional brain substrate of quality of life in patients with schizophrenia: A brain SPECT multidimensional analysis. AB - The aim of this study was to investigate the functional brain substrate of quality of life (QoL) in patients with schizophrenia. Participants comprised 130 right-handed patients with schizophrenia who underwent whole-brain single photon emission computed tomography (SPECT) with (99m)Tc-labeled ethylcysteinate dimer ((99m)Tc-ECD) for exploring correlations of regional cerebral blood flow (rCBF) with the eight dimensions score of the Schizophrenia Quality of Life questionnaire (S-QoL 18). A significant positive correlation was found between the global index of the S-QoL 18 and rCBF in the right superior temporal sulcus and between psychological well-being dimension and rCBF in Brodmann area (BA)6, BA8, BA9, and BA10 and between self-esteem dimension and rCBF in striatum and between family relationship dimension and rCBF in BA1, BA2, BA3, BA4, BA8, BA22, BA40, BA42 and BA44 and between relationship with friends dimension and rCBF in BA44 and between physical well-being dimension and rCBF in parahippocampal gyrus, and finally between autonomy dimension and rCBF in cuneus and precuneus. A significant negative correlation was found between resilience dimension and rCBF in precuneus and between sentimental life dimension and rCBF in BA10. Our findings provide neural correlates of QoL. Brain regions involved in cognitions, emotional information processing and social cognition underlie the different QoL dimensions. PMID- 27000310 TI - Sex-specific neural activity when resolving cognitive interference in individuals with or without prior internalizing disorders. AB - The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in individuals with and without an illness history of an internalizing disorder. We compared functional magnetic resonance imaging blood-oxygenation-level-dependent responses in both males (n=63) and females (n=80) with and without this illness history during performance of the Simon task. Females deactivated superior frontal gyrus, inferior parietal lobe, and posterior cingulate cortex to a greater extent than males. Females with a prior history of internalizing disorder also deactivated these regions more compared to males with that history, and they additionally demonstrated greater activation of right inferior frontal gyrus. These group differences were represented in a significant sex-by-illness interaction in these regions. These deactivated regions compose a task-negative or default mode network, whereas the inferior frontal gyrus usually activates when performing an attention-demanding task and is a key component of a task positive network. Our findings suggest that a prior history of internalizing disorders disproportionately influences functioning of the default mode network and is associated with an accompanying activation of the task-positive network in females during the resolution of cognitive interference. PMID- 27000311 TI - Dietary supplements for dysmenorrhoea. AB - BACKGROUND: Dysmenorrhoea refers to painful menstrual cramps and is a common gynaecological complaint. Conventional treatments include non-steroidal anti inflammatory drugs (NSAIDs) and oral contraceptive pills (OCPs), which both reduce myometrial activity (contractions of the uterus). A suggested alternative approach is dietary supplements. We used the term 'dietary supplement' to include herbs or other botanical, vitamins, minerals, enzymes, and amino acids. We excluded traditional Chinese medicines. OBJECTIVES: To determine the efficacy and safety of dietary supplements for treating dysmenorrhoea. SEARCH METHODS: We searched sources including the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, PsycINFO (all from inception to 23 March 2015), trial registries, and the reference lists of relevant articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of dietary supplements for moderate or severe primary or secondary dysmenorrhoea. We excluded studies of women with an intrauterine device. Eligible comparators were other dietary supplements, placebo, no treatment, or conventional analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, performed data extraction and assessed the risk of bias in the included trials. The primary outcomes were pain intensity and adverse effects. We used a fixed effect model to calculate odds ratios (ORs) for dichotomous data, and mean differences (MDs) or standardised mean differences (SMDs) for continuous data, with 95% confidence intervals (CIs). We presented data that were unsuitable for analysis either descriptively or in additional tables. We assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: We included 27 RCTs (3101 women). Most included studies were conducted amongst cohorts of students with primary dysmenorrhoea in their late teens or early twenties. Twenty-two studies were conducted in Iran and the rest were performed in other middle-income countries. Only one study addressed secondary dysmenorrhoea. Interventions included 12 different herbal medicines (German chamomile (Matricaria chamomilla, M recutita, Chamomilla recutita), cinnamon (Cinnamomum zeylanicum, C. verum), Damask rose (Rosa damascena), dill (Anethum graveolens), fennel (Foeniculum vulgare), fenugreek (Trigonella foenum-graecum), ginger (Zingiber officinale), guava (Psidium guajava), rhubarb (Rheum emodi), uzara (Xysmalobium undulatum), valerian (Valeriana officinalis), and zataria (Zataria multiflora)) and five non-herbal supplements (fish oil, melatonin, vitamins B1 and E, and zinc sulphate) in a variety of formulations and doses. Comparators included other supplements, placebo, no treatment, and NSAIDs.We judged all the evidence to be of low or very low quality. The main limitations were imprecision due to very small sample sizes, failure to report study methods, and inconsistency. For most comparisons there was only one included study, and very few studies reported adverse effects. Effectiveness of supplements for primary dysmenorrhoea We have presented pain scores (all on a visual analogue scale (VAS) 0 to 10 point scale) or rates of pain relief, or both, at the first post-treatment follow-up. Supplements versus placebo or no treatmentThere was no evidence of effectiveness for vitamin E (MD 0.00 points, 95% CI -0.34 to 0.34; two RCTs, 135 women).There was no consistent evidence of effectiveness for dill (MD -1.15 points, 95% CI -2.22 to -0.08, one RCT, 46 women), guava (MD 0.59, 95% CI -0.13 to 1.31; one RCT, 151 women); one RCT, 73 women), or fennel (MD -0.34 points, 95% CI -0.74 to 0.06; one RCT, 43 women).There was very limited evidence of effectiveness for fenugreek (MD -1.71 points, 95% CI -2.35 to -1.07; one RCT, 101 women), fish oil (MD 1.11 points, 95% CI 0.45 to 1.77; one RCT, 120 women), fish oil plus vitamin B1 (MD -1.21 points, 95% CI -1.79 to -0.63; one RCT, 120 women), ginger (MD -1.55 points, 95% CI -2.43 to -0.68; three RCTs, 266 women; OR 5.44, 95% CI 1.80 to 16.46; one RCT, 69 women), valerian (MD -0.76 points, 95% CI -1.44 to -0.08; one RCT, 100 women), vitamin B1 alone (MD -2.70 points, 95% CI -3.32 to -2.08; one RCT, 120 women), zataria (OR 6.66, 95% CI 2.66 to 16.72; one RCT, 99 women), and zinc sulphate (MD -0.95 points, 95% CI -1.54 to -0.36; one RCT, 99 women).Data on chamomile and cinnamon versus placebo were unsuitable for analysis. Supplements versus NSAIDSThere was no evidence of any difference between NSAIDs and dill (MD 0.13 points, 95% CI -1.01 to 1.27; one RCT, 47 women), fennel (MD -0.70 points, 95% CI -1.81 to 0.41; one RCT, 59 women), guava (MD 1.19, 95% CI 0.42 to 1.96; one RCT, 155 women), rhubarb (MD -0.20 points, 95% CI -0.44 to 0.04; one RCT, 45 women), or valerian (MD points 0.62 , 95% CI 0.03 to 1.21; one RCT, 99 women),There was no consistent evidence of a difference between Damask rose and NSAIDs (MD -0.15 points, 95% CI -0.55 to 0.25; one RCT, 92 women).There was very limited evidence that chamomile was more effective than NSAIDs (MD -1.42 points, 95% CI -1.69 to 1.15; one RCT, 160 women). Supplements versus other supplementsThere was no evidence of a difference in effectiveness between ginger and zinc sulphate (MD 0.02 points, 95% CI -0.58 to 0.62; one RCT, 101 women). Vitamin B1 may be more effective than fish oil (MD -1.59 points, 95% CI -2.25 to -0.93; one RCT, 120 women). Effectiveness of supplements for secondary dysmenorrhoea There was no strong evidence of benefit for melatonin compared to placebo for dysmenorrhoea secondary to endometriosis (data were unsuitable for analysis). Safety of supplements Only four of the 27 included studies reported adverse effects in both treatment groups. There was no evidence of a difference between the groups but data were too scanty to reach any conclusions about safety. AUTHORS' CONCLUSIONS: There is no high quality evidence to support the effectiveness of any dietary supplement for dysmenorrhoea, and evidence of safety is lacking. However for several supplements there was some low quality evidence of effectiveness and more research is justified. PMID- 27000313 TI - Transcriptional networks of murine diabetic peripheral neuropathy and nephropathy: common and distinct gene expression patterns. AB - AIMS/HYPOTHESIS: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) are two common microvascular complications of type 1 and type 2 diabetes mellitus that are associated with a high degree of morbidity. In this study, using a variety of systems biology approaches, our aim was to identify common and distinct mechanisms underlying the pathogenesis of these two complications. METHODS: Our previously published transcriptomic datasets of peripheral nerve and kidney tissue, derived from murine models of type 1 diabetes (streptozotocin injected mice) and type 2 diabetes (BKS-db/db mice) and their respective controls, were collected and processed using a unified analysis pipeline so that comparisons could be made. In addition to looking at genes and pathways dysregulated in individual datasets, pairwise comparisons across diabetes type and tissue type were performed at both gene and transcriptional network levels to complete our proposed objective. RESULTS: Gene-level analysis identified exceptionally high levels of concordant gene expression in DN (94% of 2,433 genes), but not in DPN (54% of 1,558 genes), between type 1 diabetes and type 2 diabetes. These results suggest that common pathogenic mechanisms exist in DN across diabetes type, while in DPN the mechanisms are more distinct. When these dysregulated genes were examined at the transcriptional network level, we found that the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway was significantly dysregulated in both complications, irrespective of diabetes type. CONCLUSIONS/INTERPRETATION: Using a systems biology approach, our findings suggest that common pathogenic mechanisms exist in DN across diabetes type, while in DPN the mechanisms are more distinct. We also found that JAK-STAT signalling is commonly dysregulated among all datasets. Using such approaches, further investigation is warranted to determine whether the same changes are observed in patients with diabetic complications. PMID- 27000312 TI - Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses. AB - Each year, 430,000 people are diagnosed with bladder cancer. Due to the high recurrence rate of the disease, primary prevention is paramount. Therefore, we reviewed all meta-analyses on modifiable risk factors of primary bladder cancer. PubMed, Embase and Cochrane database were systematically searched for meta analyses on modifiable risk factors published between 1995 and 2015. When appropriate, meta-analyses (MA) were combined in meta-meta-analysis (MMA). If not, the most comprehensive MA was selected based on the number of primary studies included. Probability of causation was calculated for individual factors and a subset of lifestyle factors combined. Of 1496 articles identified, 5 were combined in MMA and 21 were most comprehensive on a single risk factor. Statistically significant associations were found for current (RR 3.14) or former (RR 1.83) cigarette smoking, pipe (RR 1.9) or cigar (RR 2.3) smoking, antioxidant supplementation (RR 1.52), obesity (RR 1.10), higher physical activity levels (RR 0.86), higher body levels of selenium (RR 0.61) and vitamin D (RR 0.75), and higher intakes of: processed meat (RR 1.22), vitamin A (RR 0.82), vitamin E (RR 0.82), folate (RR 0.84), fruit (RR 0.77), vegetables (RR 0.83), citrus fruit (RR 0.85), and cruciferous vegetables (RR 0.84). Finally, three occupations with the highest risk were tobacco workers (RR 1.72), dye workers (RR 1.58), and chimney sweeps (RR 1.53). The probability of causation for individual factors ranged from 4 to 68 %. The combined probability of causation was 81.8 %. Modification of lifestyle and occupational exposures can considerably reduce the bladder cancer burden. While smoking remains one of the key risk factors, also several diet related and occupational factors are very relevant. PMID- 27000314 TI - Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis. AB - BACKGROUND: Eosinophilic esophagitis (EoE) has been defined as "asthma of the esophagus" for the large number of similarities between the two diseases. Omalizumab is an anti-Immunoglobulin E (IgE) antibody currently approved only in allergic IgE-mediated severe persistent uncontrolled asthma and in chronic spontaneous urticaria unresponsive to antihistamines, but it has been tried in other diseases, too. CASE PRESENTATION: We present herein the case of a 13-year old boy, affected from preschool age by severe chronic allergic asthma poorly controlled despite a generous long-term therapy, and, since he was 8 years old, by eosinophilic esophagitis, responsive to courses of strict elimination diet and semi-elemental diet, even if very burdensome for his quality of life. At the age of 11.5 years, for inadequate asthma control, he started to receive therapy with omalizumab. After the first month and for the entire duration (18 months) of omalizumab treatment, asthma was well controlled, long-term conventional therapy was gradually withdrawn and lung- function improved. Concerning EoE, after an initial clinical but not histological remission during the first few months of treatment with omalizumab, the patient experienced an exacerbation of gastrointestinal symptoms. Therefore, he started treatment with topical steroids which was effective to improve gastrointestinal symptoms. However, EoE is still steroid-dependent. Currently, he continues both treatments: omalizumab for asthma and topical steroid for EoE. CONCLUSIONS: This case report confirms that omalizumab is an effective treatment in patients with severe persistent, uncontrolled asthma. On the other hand, in our patient it did not produce persistent improvement neither on symptoms nor on biopsy findings of EoE. The outcome of this case might indicate different pathogenic mechanism(s) of the two diseases. PMID- 27000316 TI - Environmental impact assessment using a GSR tool for a landfarming case in South Korea. AB - An environmental impact assessment of a landfarming process, which was performed at an actual petroleum-contaminated site, was conducted using a green and sustainable remediation (GSR) tool in this study. The landfarming process was divided into four stages: site preparation, installation, system operation, and system dismantling/waste disposal. The environmental footprints of greenhouse gas (GHG) emissions, water consumption, total energy usage, and air pollutants (SOx, NOx, and PM10) were analyzed. GHG emissions and water consumption were approximately 276 metric tons and 7.90E + 05 gal, respectively, in stage III, where they were the highest due to the consumables and equipment use in the system operation. Total energy usage had the highest value of 1.54E + 03 MMBTU in stage II due to material production. The SOx and NOx emissions primarily occurred in stages I and II due to energy usage. The PM10 was mostly emitted in stages I and III and was associated with heavy use of equipment. To reduce the environmental footprints, biodiesel and sunlight were suggested as alternatives in this study. The GHG and SOx emissions decreased to 1.7 and 4.4E-04 metric tons, respectively, on the basis of total emissions with a 1 % increase in biodiesel content, but the NOx emissions increased to 5.6E-03 metric tons. If sunlight was used instead of electricity, the GHG and NOx emissions could be reduced by as much as 79 and 84 %, respectively, and the SOx emissions could also be reduced. PMID- 27000315 TI - Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities. AB - BACKGROUND: It is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. METHODS: In a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV). Heterogeneity of ventilation was calculated as the coefficient of variation in sV (CVsV ). The coefficient of variation in lung densities (CVD ) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FI O2 0.21; ZEEP and FI O2 1.0; PEEP 12 cmH2 O and FI O2 1.0 (Open Lung-PEEP = OLP). RESULTS: The mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV and poor aeration at ZEEP-0.21 than at OLP: 12.9 +/ 9.0 vs. 0.6 +/- 0.4% in the non-dependent level, and 17.5 +/- 8.2 vs. 0.4 +/- 0.1% in the dependent one (P = 0.041). The CVsV of the total imaged lung at PEEP 12 cmH2 O was significantly lower than on ZEEP, regardless of FI O2 , indicating more heterogeneity of ventilation during ZEEP (0.23 +/- 0.03 vs. 0.54 +/- 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. CONCLUSION: ZEEP together with low FI O2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions. PMID- 27000317 TI - Evaluating the primary and ready biodegradability of dianilinodithiophosphoric acid. AB - Dianilinodithiophosphoric acid (DDA) is widely used as sulfide mineral flotation collector in China. It is necessary to investigate the biodegradability of DDA to provide the fundamental knowledge to assess the environmental fate in the risk assessment of DDA and to design and operate the DDA flotation wastewater biological treatment plant. In the present study, the primary and ready aerobic biodegradations of DDA were studied and the primary biodegradation kinetic model of DDA was developed. The results show that DDA displays a good primary biodegradability and its biodegradation ratio reaches 99.8 % in 7 days. In contrast, DDA is not easily ready biodegradable; hence, it is a partially biodegradable organic compound. The primary aerobic biodegradation kinetics can be described using the first-order reaction kinetics equation: C = 19.72191e( 0.01513t). PMID- 27000318 TI - Investigating the salinization and freshening processes of coastal groundwater resources in Urmia aquifer, NW Iran. AB - This paper presents the results of an assessment about interaction between Urmia Lake (UL) and coastal groundwater in the Urmia aquifer (UA). This aquifer is the most significant contributor to the freshwater supply of the coastal areas. The use of hydrochemical facies can be very useful to identify the saltwater encroachment or freshening phases in the coastal aquifers. In this study, the analysis of salinization/freshening processes was carried out through the saturation index (SI), ionic deltas (Delta), binary diagrams, and hydrochemical facies evolution (HFE) diagram. Based on the Gibbs plot, the behavior of the major ions showed that the changes in the chemical composition of the groundwater are mainly controlled by the water-soil/rock interaction zone and few samples are relatively controlled by evaporation. A possible explanation for this phenomenon is that the deposited chloride and sulfate particles can form the minor salinity source in some coastal areas when washed down by precipitation. The SI calculations showed that all groundwater samples, collected in these periods, show negative saturation indices, which indicate undersaturation with respect to anhydrite, gypsum, and halite. In addition, except in a few cases, all other samples showed the undersaturation with respect to the carbonate minerals such as aragonite, calcite, and dolomite. Therefore, these minerals are susceptible to dissolution. In the dry season, the SI calculations showed more positive values with respect to dolomite, especially in the northern part of UA, which indicated a higher potential for precipitation and deposition of dolomite. The percentage of saltwater in the groundwater samples of Urmia plain was very low, ranging between 0.001 and 0.79 % in the wet season and 0.0004 and 0.81 % in the dry season. The results of HFE diagram, which was taken to find whether the aquifer was in the saltwater encroachment phase or in the freshening phase, indicated that except for a few wells near the coast, there is very little hydraulic interaction between UA and UL. In this coastal area, most of the samples that were collected repeatedly in both wet and dry seasons showed the same hydrochemical facies, which suggested that the seasonal groundwater fluctuations cannot significantly change the chemical composition of groundwater. PMID- 27000319 TI - Chemical characterisation of dredged sediments in relation to their potential use in civil engineering. AB - During capital and/or maintenance dredging operations, large amounts of material are produced. Instead of their discharge, dredged sediments may be a valuable natural resource if not contaminated. One of the possible areas of application is civil engineering. In the present work, the environmental status of seaport dredged sediment was evaluated in order to investigate its potential applicability as a secondary raw material. Sediments were analysed for element concentrations in digested samples, aqueous extracts and fractions from sequential extraction; for fluoride, chloride and sulphate concentrations in aqueous extracts; and for tributyltin (TBT). Granulometric and mineralogical compositions were also analysed. The elemental impact was evaluated by calculation of the enrichment factors. The total element concentrations determined showed moderate contamination of the dredged sediments as was confirmed also by their moderate enrichment factors, presumably as a result of industrial and port activities. Elemental concentrations in the aqueous extract were very low and therefore do not represent any hazard for the environment. The water-soluble element concentrations were under the threshold levels set by the EU Directive on the landfill of waste, on the basis of which the applicability of dredged sediments in civil engineering is evaluated, while the content of chloride and sulphate were above the threshold levels. It was found out that due to the large amounts of sediment available, civil engineering applications such as the construction of embankments and backfilling is the most beneficial recycling solution at present. PMID- 27000320 TI - Phytostabilization of arsenic in soils with plants of the genus Atriplex established in situ in the Atacama Desert. AB - In the ChiuChiu village (Atacama Desert, Chile), there is a high concentration of arsenic (As) in the soil due to natural causes related to the presence of volcanoes and geothermal activity. To compare the levels of As and the growth parameters among plants of the same genus, three species of plants were established in situ: Atriplex atacamensis (native of Chile), Atriplex halimus, and Atriplex nummularia. These soils have an As concentration of 131.2 +/- 10.4 mg kg(-1), a pH of 8.6 +/- 0.1, and an electrical conductivity of 7.06 +/- 2.37 dS m(-1). Cuttings of Atriplex were transplanted and maintained for 5 months with periodic irrigation and without the addition of fertilizers. The sequential extraction of As indicated that the metalloid in these soils has a high bioavailability (38 %), which is attributed to the alkaline pH, low organic matter and Fe oxide content, and sandy texture. At day 90 of the assay, the As concentrations in the leaves of A. halimus (4.53 +/- 1.14 mg kg(-1)) and A. nummularia (3.85 +/- 0.64 mg kg(-1)) were significantly higher than that in A. atacamensis (2.46 +/- 1.82 mg kg(-1)). However, the three species accumulated higher levels of As in their roots, indicating a phytostabilization capacity. At the end of the assay, A. halimus and A. nummularia generated 30 % more biomass than A. atacamensis without significant differences in the As levels in the leaves. Despite the difficult conditions in these soils, the establishment of plants of the genus Atriplex is a recommended strategy to generate a vegetative cover that prevents the metalloid from spreading in this arid area through the soil or by wind. PMID- 27000321 TI - Care-Delivery Interventions to Manage Agitation and Aggression in Dementia Nursing Home and Assisted Living Residents: A Systematic Review and Meta analysis. AB - OBJECTIVES: To evaluate the efficacy of nonpharmacological care-delivery interventions (staff training, care-delivery models, changes to the environment) to reduce and manage agitation and aggression in nursing home and assisted living residents. DESIGN: Three bibliographic databases, references of systematic reviews, ClincalTrials.gov, and the International Controlled Trials Registry Platform were systematically searched for randomized controlled trials reporting behavioral outcomes for nonpharmacological care-delivery interventions in nursing homes and assisted living facilities. Five investigators independently assessed study eligibility, extracted data, rated risk of bias, and graded strength of evidence. Inclusion was limited to studies with low to moderate risk of bias. SETTING: Nursing homes and assisted living facilities. PARTICIPANTS: Facility caregiving staff. MEASUREMENTS: Agitation, aggression, antipsychotic and other psychotropic use, general behavior. RESULTS: Nineteen unique studies met entry criteria, addressing several categories of facility caregiver training interventions: dementia care mapping (DCM; n = 3), person-centered care (PCC; n = 3), clinical protocols to reduce the use of antipsychotic and other psychotropic drugs (n = 3), and emotion-oriented care (n = 2). Eleven additional studies evaluated other unique interventions. Results were pooled for the effect of each type of intervention on agitation and aggression: DCM (standardized mean difference -0.12, 95% confidence interval (CI) = -0.66 to 0.42), PCC (standardized mean difference -0.15, 95% CI = -0.67 to 0.38), and protocols to reduce antipsychotic and other psychotropic use (Cohen-Mansfield Agitation Inventory mean difference -4.5, 95% C = -38.84 to 29.93). Strength of evidence was generally insufficient to draw conclusions regarding efficacy or comparative effectiveness. CONCLUSION: Evidence was insufficient regarding the efficacy of nonpharmacological care-delivery interventions to reduce agitation or aggression in nursing home and assisted living facility residents with dementia. PMID- 27000322 TI - Managing Agitation and Aggression in Congregate Living Settings: Efficacy and Implementation Challenges. PMID- 27000323 TI - Anticholinergic Drug Burden in Persons with Dementia Taking a Cholinesterase Inhibitor: The Effect of Multiple Physicians. AB - OBJECTIVES: To explore the association between the number of physicians providing care and anticholinergic drug burden in older persons newly initiated on cholinesterase inhibitor therapy for the management of dementia. DESIGN: Population-based cross-sectional study. SETTING: Community and long-term care, Ontario, Canada. PARTICIPANTS: Community-dwelling (n = 79,067, mean age 81.0, 60.8% female) and long-term care residing (n = 12,113, mean age 84.3, 67.2% female) older adults (>=66) newly dispensed cholinesterase inhibitor drug therapy. MEASUREMENTS: Anticholinergic drug burden in the prior year measured using the Anticholinergic Risk Scale. RESULTS: Community-dwelling participants had seen an average of eight different physicians in the prior year. The odds of high anticholinergic drug burden (Anticholinergic Risk Scale score >= 2) were 24% higher for every five additional physicians providing care to individuals in the prior year (adjusted odds ratio = 1.24, 95% confidence interval = 1.21-1.26). Female sex, low-income status, previous hospitalization, and higher comorbidity score were also associated with high anticholinergic drug burden. Long-term care facility residents had seen an average of 10 different physicians in the prior year. After a sensitivity analysis, the association between high anticholinergic burden and number of physicians was no longer statistically significant in the long-term care group. CONCLUSION: In older adults newly started on cholinesterase inhibitor drug therapy, greater number of physicians providing care was associated with higher anticholinergic drug burden scores. Given the potential risks of anticholinergic drug use, improved communication among physicians and an anticholinergic medication review before prescribing a new drug are important strategies to improve prescribing quality. PMID- 27000324 TI - Effect of Structured Physical Activity on Respiratory Outcomes in Sedentary Elderly Adults with Mobility Limitations. AB - OBJECTIVES: To evaluate the effect of structured physical activity on respiratory outcomes in community-dwelling elderly adults with mobility limitations. DESIGN: Multicenter, randomized trial of physical activity vs health education, with respiratory variables prespecified as tertiary outcomes over an intervention period of 24-42 months. Physical activity included walking (goal of 150 min/week) and strength, flexibility, and balance training. Health education included workshops on topics relevant to older adults and upper extremity stretching exercises. SETTING: Lifestyle Interventions and Independence in Elders (LIFE) Study. PARTICIPANTS: Community-dwelling persons aged 70-89 with Short Physical Performance Battery scores less than 10 (N = 1,635). MEASUREMENTS: Dyspnea severity (defined as moderate to severe according to a Borg index >2 immediately after a 400-m walk), forced expiratory volume in 1 second (FEV1) (=75). Safety was assessed based on adverse event (AE) reports from eight randomized, double-blind, placebo- and active-controlled studies (N = 9,439; n = 8,949 aged <75, n = 490 aged >=75). RESULTS: Canagliflozin 100 and 300 mg were associated with placebo-subtracted mean reductions in HbA1c in participants younger than 75 (-0.69% and -0.85%, respectively) and aged 75 and older (-0.65% and -0.55%, respectively). Dose-related reductions in FPG, body weight, and BP were seen with canagliflozin 100 and 300 mg in participants in both age groups. Overall AE incidence was 67.1% with canagliflozin 100 mg, 68.6% with canagliflozin 300 mg, and 65.9% with non-canagliflozin (pooled group of comparators in all studies) in participants younger than 75, and 72.4%, 79.1%, and 72.3%, respectively, in those aged 75 and older, with a similar safety profile in both groups. The incidence of volume depletion-related AEs was 2.2%, 3.1%, and 1.4% in participants younger than 75 with canagliflozin 100 and 300 mg and non-canagliflozin, respectively, and 4.9%, 8.7%, and 2.6%, respectively, in those aged 75 and older. CONCLUSION: Canagliflozin improved glycemic control, body weight, and BP in participants aged 75 and older. The overall incidence of AEs was high across treatment groups in participants aged 75 and older and higher than in those younger than 75. The safety profile of canagliflozin was generally similar in both age groups, with a higher incidence of AEs related to volume depletion observed with canagliflozin in participants aged 75 and older than in those younger than 75. These findings support canagliflozin, starting with the 100-mg dose, as an effective therapeutic option for older adults with T2DM. PMID- 27000328 TI - Relationship Between Circulating Thyroid-Stimulating Hormone, Free Thyroxine, and Free Triiodothyronine Concentrations and 9-Year Mortality in Euthyroid Elderly Adults. AB - OBJECTIVES: To determine the association between plasma thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and all-cause mortality in older adults who had levels of all three hormones in the normal range. DESIGN: Longitudinal. SETTING: Community-based. PARTICIPANTS: Euthyroid Invecchiare in Chianti study participants aged 65 and older (N = 815). MEASUREMENTS: Plasma TSH, FT3, and FT4 levels were predictors, and 9-year all cause mortality was the outcome. Cox proportional hazards models adjusted for confounders were used to examine the relationship between TSH, FT3, and FT4 quartiles and all-cause mortality over 9 years of follow-up. RESULTS: During follow-up (mean person-years 8,643.7, range 35.4-16,985.0), 181 deaths occurred (22.2%). Participants with TSH in the lowest quartile had higher mortality than the rest of the population. After adjusting for multiple confounders, participants with TSH in the lowest quartile (hazard ratio = 2.22, 95% confidence interval = 1.19-4.22) had significantly higher all-cause mortality than those with TSH in the highest quartile. Neither FT3 nor FT4 was associated with mortality. CONCLUSION: In elderly euthyroid subjects, normal-low TSH is an independent risk factor for all-cause mortality. PMID- 27000329 TI - Multifaceted Prospective Memory Intervention to Improve Medication Adherence. AB - OBJECTIVES: To test whether a multifaceted prospective memory intervention improved adherence to antihypertensive medications and to assess whether executive function and working memory processes moderated the intervention effects. DESIGN: Two-group longitudinal randomized control trial. SETTING: Community. PARTICIPANTS: Individuals aged 65 and older without signs of dementia or symptoms of severe depression who were self-managing prescribed medication. MEASUREMENTS: After 4 weeks of initial adherence monitoring using a medication event monitoring system, individuals with 90% or less adherence were randomly assigned to groups. INTERVENTION: The prospective memory intervention was designed to provide strategies that switch older adults from relying on executive function and working memory processes (that show effects of cognitive aging) to mostly automatic associative processes (that are relatively spared with normal aging) for remembering to take medications. Strategies included establishing a routine, establishing cues strongly associated with medication taking actions, performing the action immediately upon thinking about it, using a medication organizer, and imagining medication taking to enhance encoding and improve cuing. RESULTS: There was significant improvement in adherence in the intervention group (57% at baseline to 78% after the intervention), but most of these gains were lost after 5 months. The control condition started at 68% and was stable during the intervention, but dropped to 62%. Executive function and working memory moderated the intervention effect, with the intervention producing greater benefit for those with lower executive function and working memory. CONCLUSION: The intervention improved adherence, but the benefits were not sustained. Further research is needed to determine how to sustain the substantial initial benefits. PMID- 27000330 TI - Diagnosis and Disruption: Population-Level Analysis Identifying Points of Care at Which Transitions Are Highest for People with Dementia and Factors That Contribute to Them. AB - OBJECTIVES: To examine transitions that individuals with dementia experience longitudinally and to identify points of care when transitions are highest and the factors that contribute to those transitions. DESIGN: Population-based 10 year retrospective cohort study from 2000 to 2011. SETTING: General community. PARTICIPANTS: All individuals aged 65 and older newly diagnosed with dementia in British Columbia, Canada. MEASUREMENTS: The frequency and timing of transitions over 10 years, participant characteristics associated with greater number of transitions, and the influence of recommended dementia care and high-quality primary care on number of transitions. RESULTS: Individuals experience a spike in transitions during the year of diagnosis, driven primarily by hospitalizations, despite accounting for end of life or newly moving to a long-term care facility (LTCF). This occurs regardless of survival time or care location. Regardless of survival time, individuals not in LTCFs experience a marked increase in hospitalizations in the year before and the year of death, often exceeding hospitalizations in the year of diagnosis. Receipt of recommended dementia care and receipt of high-quality primary care were independently associated with fewer transitions across care settings. CONCLUSION: The spike in transitions in the year of diagnosis highlights a distressing period for individuals with dementia during which unwanted or unnecessary transitions might occur and suggests a useful target for interventions. There is an association between recommended dementia care and outcomes and evidence of the continued value of high-quality primary care in a complex population at a critical point when gaps in continuity are especially likely. PMID- 27000331 TI - Religious Involvement and Adaptation in Female Family Caregivers. AB - OBJECTIVES: To examine the relationship between religious involvement (RI) and adaptation of women caring for family members with severe physical or neurological disability. DESIGN: Two-site cross-sectional study. SETTING: Community. PARTICIPANTS: A convenience sample of 251 caregivers was recruited. RI and caregiver adaptation (assessed by perceived stress, caregiver burden, and depressive symptoms) were measured using standard scales, along with caregiver characteristics, social support, and health behaviors. Bivariate and multivariate analyses were conducted to identify relationships and mediating and moderating factors. RESULTS: Religious involvement (RI) was associated with better caregiver adaptation independent of age, race, education, caregiver health, care recipient's health, social support, and health behaviors (B = -0.09, standard error = 0.04, t = -2.08, P = .04). This association was strongest in caregivers aged 58-75 and spouses and for perceived stress in blacks. CONCLUSION: Religious involvement (RI) in female caregivers is associated with better caregiver adaptation, especially for those who are older, spouses of the care recipients, and blacks. These results are relevant to the development of future interventions that provide support to family caregivers. PMID- 27000332 TI - Prediction of Cognitive and Functional Decline Using the Telephone-Administered Minnesota Cognitive Acuity Screen. AB - OBJECTIVES: To examine whether a telephone-based cognitive assessment-the Minnesota Cognitive Acuity Screen (MCAS)-is effective in predicting cognitive and functional decline in older adults with mild cognitive impairment (MCI) and conversion to dementia. DESIGN: Longitudinal. SETTING: Academic medical center. PARTICIPANTS: Individuals aged 60 to 84 with MCI (N = 61). MEASUREMENTS: An initial office visit consisting of a neurological examination, Clinical Dementia Rating Scale (CDR), and neuropsychological testing using the Dementia Rating Scale-2 (DRS-2), followed by the MCAS within 1 month. Participants completed up to three follow-up in-office neuropsychological assessments, originally scheduled 1 year apart. A multidisciplinary consensus group determined diagnosis (MCI, dementia) at each assessment. RESULTS: Higher baseline MCAS total scores emerged as a significant predictor of slower functional decline (P = .002) and dementia conversion (P = .02). An increase in score from 43 to 50 points (1st to 3rd quartile) was associated with a 0.59-point (95% confidence interval (CI) = 0.23 0.95) lower CDR score at follow-up, and a 71% (95% CI = 1.11-2.63) increase in median time to dementia conversion from 2 years to 3.5 years. Of the MCAS subscales, delayed word recall predicted functional decline alone (P < .001), whereas computation was nominally associated with cognitive (P = .01) and functional (P = .01) decline. CONCLUSION: The brief telephone-administered MCAS provides valuable information about future cognitive and functional decline in older adults with MCI and predicted conversion from MCI to dementia. These findings provide additional support for use of MCAS in clinical and research settings. The instrument may be particularly valuable in settings in which an office visit is difficult. PMID- 27000333 TI - Hospital Readmission Penalties: Coming Soon to a Nursing Home Near You! AB - The Protecting Access to Medicare Act of 2014 includes provisions for hospital readmission penalties for skilled nursing facilities (SNFs) starting in 2018. This presents an opportunity for care improvement but also raises several concerns regarding quality of care. The readmission measure for SNFs is similar to the current readmission measure for hospitals mandated under the Affordable Care Act, with the exception of adjustments made for sex. Because these measures for hospitals are similar, lessons can be learned from implementation of the existing hospital readmission penalties. In addition, there are three specific concerns that the authors relate to implementing the proposed measure in SNFs. There is poor communication and care coordination between care settings, including posthospitalization and post-SNF care in the current healthcare system. Adding readmission penalties to SNF regulations may create perverse incentives for prolonged SNF stays. The evidence base for the best means of caring for individuals after a brief stay in a SNF needs enrichment. These challenges need to be addressed as part of implementation of these new hospital readmission penalties for SNFs to improve care and prevent new unintended consequences. PMID- 27000334 TI - Diabetes Mellitus as a Risk Factor for Development of Depressive Symptoms in a Population-Based Cohort of Older Mexican Americans. AB - OBJECTIVES: To determine whether diabetes mellitus increases depressive symptoms in older Latinos in a population-based cohort. DESIGN: Prospective cohort study. PARTICIPANTS: Individuals from the Sacramento Latino Study on Aging aged 60 and older in 1998-99 and followed annually until 2008 (N = 1,586). MEASUREMENTS: Diabetes mellitus was defined according to self-report, fasting blood glucose of 126 mg/dL or greater, glycosylated hemoglobin of 6.5% or greater, or diabetic medication use. Depressive symptoms were defined as Center for Epidemiologic Studies Depression Scale (CES-D) score of 16 or greater or use of antidepressant medication. Multistate Markov modeling was used to assess the effects of time dependent diabetes mellitus on transitions between three states over time: low CES-D score (normal), high CES-D score or treated (depressed), and death. Bivariate analyses identified covariates significantly associated with any transition, including sex and baseline measures of age, education, body mass index, hypertension, and stroke. RESULTS: In a fully adjusted model, participants with diabetes mellitus had a 35% higher rate of developing depressive symptoms or starting treatment with an antidepressant (hazard ratio (HR) = 1.35, 95% confidence interval (CI) = 1.13-1.62). Time-dependent diabetes mellitus was associated with a lower rate of regression from depressed to normal (HR = 0.72, 95% CI = 0.59-0.88) and a 2.3 greater rate pf progression from depressed to death (HR = 2.31, 95% CI = 1.57-3.40). CONCLUSION: Diabetes mellitus increased the risk of developing depressive symptoms in older Mexican Americans. Older Latinos with diabetes mellitus should be screened for depressive symptoms and prioritized for close follow-up, potentially through greater reliance on team-based models of care. PMID- 27000335 TI - Health Values and Treatment Goals of Older, Multimorbid Adults Facing Life Threatening Illness. AB - OBJECTIVES: To identify a taxonomy of health-related values that frame goals of care of older, multimorbid adults who recently faced cancer diagnosis and treatment. DESIGN: Qualitative analysis of data from a longitudinal cohort study of multimorbid cancer survivors. SETTING: Cancer registries from regional Department of Veterans Affairs networks in New England and southeast Texas. PARTICIPANTS: Multimorbid adults who completed interviews 12 months after diagnosis of head and neck, colorectal, gastric, or esophageal cancer and after cancer treatment (N = 146). MEASUREMENTS: An interdisciplinary team conducted thematic analyses of participants' intuitive responses to two questions: Now that you have had cancer and may face ongoing decisions about medical care in the future, what would you want your family, friends, and doctors to know about you, in terms of what is most important to you in your life? If your cancer were to recur, is there anything you'd want to be sure your loved ones knew about you and your goals of care? RESULTS: Analysis revealed five distinct health-related values that guide how multimorbid cancer survivors conceptualize specific health care goals and medical decisions: self-sufficiency, life enjoyment, connectedness and legacy, balancing quality and length of life, and engagement in care. Participants typically endorsed more than one value as important. CONCLUSION: Older multimorbid adults who recently faced life-threatening cancer endorsed a multidimensional taxonomy of health-related values. These health-related values guide how they frame their goals for care and treatment preferences. Eliciting individuals' sense of their values during clinical encounters may improve their experiences with health care and more effectively align treatments with goals of care. PMID- 27000336 TI - Common Components of Efficacious In-Home End-of-Life Care Programs: A Review of Systematic Reviews. AB - Multiple randomized controlled trials on in-home end-of-life (EOL) programs, often with multifaceted and varying components, have shown benefits and reduced costs. The objective of this review was to determine which components of these programs are most commonly associated with better outcomes than usual care. MEDLINE, CINAHL, and the Cochrane Library databases were searched from 2003 to 2014 for reviews of studies of in-home programs treating individuals with advanced illness. Original quantitative studies were included from these reviews, and the details of every program that had a significant positive effect on any outcome measured were extracted. Nineteen reviews met the inclusion criteria, from which 40 relevant studies were identified. Thirty unique components emerged from the content analysis of the program descriptions. On average, each program contained 11 components; the six most common were linkage with acute care, multidisciplinary nature, EOL expertise and training, holistic care, pain and symptom management, and professional psychosocial support. Linkage, around-the clock availability, and customized care planning were most common to the nine interventions for which a significant cost reduction was reported. Efficacious in home EOL programs comprised multiple components. Knowledge of these features can help inform the design of this care in local contexts that will more likely improve outcomes for individuals in an effective and cost-efficient manner. PMID- 27000337 TI - Precious Memory. PMID- 27000338 TI - Demented Love. PMID- 27000339 TI - She Saved My Life. PMID- 27000340 TI - The Physical Exam and Touch. PMID- 27000341 TI - Value of Physical Activity and Sedentary Behavior in Predicting Depression in Older Adults. PMID- 27000342 TI - Community-Acquired Pneumonia in Elderly Adults with Type 2 Diabetes Mellitus. PMID- 27000343 TI - Using International Classification of Diseases Codes to Track Medication-Related Hospitalizations of Older Adults. PMID- 27000344 TI - Medication Discrepancies and Shared Decision-Making. PMID- 27000345 TI - Peripheral Inflammation and Functional Decline in the National Health and Nutrition Examination Survey Elderly Population. PMID- 27000346 TI - Frailty in Four Ethnic Groups in South Florida. PMID- 27000347 TI - Adherence to Long-Term Drug Regimen After Hospital Discharge: General Practitioners' Attitude. PMID- 27000348 TI - Preserving Cognition in Older African Americans with Mild Cognitive Impairment. PMID- 27000349 TI - Verification of Educational Support Intervention for Family Caregivers of Persons with Dementia. PMID- 27000350 TI - Naloxone Treatment for Poststroke Agitated Delirium in Hospitalized Older Adults: A Pilot Study. PMID- 27000351 TI - Macrolide Therapy for Prevention of Exacerbation in Individuals with Diffuse Aspiration Bronchiolitis. PMID- 27000352 TI - Recruitment for an Advance Care Planning Study: Lessons Learned. PMID- 27000353 TI - Use of Proton Pump Inhibitors and Risk of Nosocomial Clostridium Difficile Infection in Hospitalized Elderly Adults. PMID- 27000354 TI - Overuse of Vitamin B12 Supplementation in French Nursing Homes. PMID- 27000355 TI - Association Between Anticholinergic Load and Frailty in Community-Dwelling Older People. PMID- 27000356 TI - Immunosuppressive Therapy (Methotrexate or Cyclophosphamide) in Combination with Corticosteroids in the Treatment of Giant Cell Arteritis: Comparison with Corticosteroids Alone. PMID- 27000357 TI - Explaining Improved Use of High-Risk Medications in Medicare Between 2007 and 2011. PMID- 27000358 TI - Complications of Fiberoptic Bronchoscopy in Very Elderly Adults. PMID- 27000359 TI - Health Status of Elderly Adults Living in Rural Turkey. PMID- 27000360 TI - Evolving Patterns of Intensive Care Unit Use During End-of-Life Hospitalization in Elderly Adults with Dementia in Texas: A Population-Based Study. PMID- 27000361 TI - Pushing Age Limits Forward: How Should Acute Coronary Syndromes Be Treated in Centenarians? Discussion of Some Clinical Cases. PMID- 27000362 TI - Esophageal Rupture Associated with Colonoscopy Preparation. PMID- 27000363 TI - Mild Cognitive Impairment as the Initial Manifestation of Progressive Supranuclear Palsy. PMID- 27000364 TI - Zoonosis in the Nursing Home. PMID- 27000365 TI - Delayed Diagnosis of Acromegaly in an Elderly Adult that Initially Presented as Cutis Verticis Gyrata. PMID- 27000366 TI - Improved Glycemic Control and Vascular Function and Reduction of Abdominal Fat Accumulation with Liraglutide in a Case of Werner Syndrome with Diabetes Mellitus. PMID- 27000367 TI - Incarcerated Incisional Hernia: Strangulated Transverse Colon with Perforation Associated with Abscess Formation. PMID- 27000368 TI - Markers of Visceral Adiposity for Dementia Risk Assessment. The Epicardial Adipose Tissue (EAT) Thickness. PMID- 27000369 TI - Cochlear Implantation in Elderly Adults. PMID- 27000370 TI - Embolism Risk Versus Stroke Risk: More Than a Matter of Semantics. PMID- 27000371 TI - Elderly Adults Not Chosen for Society for General Internal Medicine Choosing Wisely Recommendation. PMID- 27000372 TI - Artifact in Barium Swallow Study in an Individual with Dysphagia Aortica. PMID- 27000375 TI - The Hair Follicle: A Comparative Review of Canine Hair Follicle Anatomy and Physiology. AB - The hair follicle (HF) has a wide range of functions including thermoregulation, physical and immunological protection against external insults, sensory perception, social interactions, and camouflage. One of the most characteristic features of HFs is that they self-renew during hair cycle (HC) throughout the entire life of an individual to continuously produce new hair. HC disturbances are common in humans and comparable to some alopecic disorders in dogs. A normal HC is maintained by follicular stem cells (SCs), which are predominately found in an area known as the bulge. Due to similar morphological characteristics of the human and canine bulge area, the particularity of compound HFs in humans and dogs as well as similarities in follicular biomarker expression, the dog might be a promising model to study human HC and SC disorders. In this review, we give an overview of normal follicular anatomy, the HC, and follicular SCs and discuss the possible pathogenetic mechanisms of noninflammatory alopecia. PMID- 27000374 TI - COX-2 modulates mammary tumor progression in response to collagen density. AB - BACKGROUND: High breast density is linked to an increased risk of breast cancer, and correlates with changes in collagen. In a mouse model of mammary carcinoma in the context of increased collagen deposition, the MMTV-PyMT/Col1a1 (tm1jae) , there is accelerated mammary tumor formation and progression. Previous gene expression analysis suggests that increased collagen density elevates expression of PTGS2 (prostaglandin-endoperoxide synthase 2), the gene for cyclooxygenase-2 (COX-2). METHODS: To understand the role of COX-2 in tumor progression within a collagen-dense microenvironment, we treated MMTV-PyMT or MMTV-PyMT/Col1a1 (tm1jae) tumors prior to and after tumor formation. Animals received treatment with celecoxib, a specific COX-2 inhibitor, or placebo. Mammary tumors were examined for COX-2, inflammatory and stromal cell components, and collagen deposition through immunohistochemical analysis, immunofluorescence, multiplex cytokine ELISA and tissue imaging techniques. RESULTS: PyMT/Col1a1 (tm1jae) tumors were larger, more proliferative, and expressed higher levels of COX-2 and PGE2 than PyMT tumors in wild type (WT) mice. Treatment with celecoxib significantly decreased the induced tumor size and metastasis of the PyMT/Col1a1 tumors, such that their size was not different from the smaller PyMT tumors. Celecoxib had minimal effect on the PyMT tumors. Celecoxib decreased expression levels of COX-2, PGE2, and Ki-67. Several cytokines were over-expressed in PyMT/Col1a1 compared to PyMT, and celecoxib treatment prevented their over expression. Furthermore, macrophage and neutrophil recruitment were enhanced in PyMT/Col1a1 tumors, and this effect was inhibited by celecoxib. Notably, COX-2 inhibition reduced overall collagen deposition. Finally, when celecoxib was used prior to tumor formation, PyMT/Col1a1 tumors were fewer and smaller than in untreated animals. CONCLUSION: These findings suggest that COX-2 has a direct role in modulating tumor progression in tumors arising within collagen-dense microenvironments, and suggest that COX-2 may be an effective therapeutic target for women with dense breast tissue and early-stage breast cancer. PMID- 27000376 TI - Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice: An NTP Retrospective Study. AB - Due to potential misdiagnosis of hyaline glomerulopathy (HG) for amyloidosis, a retrospective study of B6C3F1 mice from the National Toxicology Program (NTP) archives was undertaken to determine whether HG had occurred in prior NTP studies and, if so, whether these 2 glomerular lesions could be routinely discriminated. Kidney slides from 7 amyloid-positive control mice, 2 HG-positive control mice, 3 normal or negative control mice, and 41 potential HG mice (with renal-only deposits previously diagnosed as amyloid) were evaluated using hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Congo red (CR), and Masson's trichrome (MT) stains. Utilizing these techniques, HG was reliably distinguished from amyloidosis. All 41 potential HG mice had glomerular deposits histochemically inconsistent with amyloid; the deposits were PAS positive and CR negative. Four of the 41 mice were selected for transmission electron microscopy of the glomerular deposits; ultrastructurally, the deposits in these animals were consistent with HG and not amyloid. Our findings indicate that HG is a spontaneous lesion in B6C3F1 mice of low occurrence, is commonly misdiagnosed as amyloidosis, and is more likely than amyloid to cause glomerular deposits in mice without evidence of deposits in other tissues. Also, HG can be distinguished from amyloid on H&E evaluation; however, the distinction is improved with use of PAS or CR staining and/or ultraviolet evaluation. PMID- 27000377 TI - Conarticular congruence of the hominoid subtalar joint complex with implications for joint function in Plio-Pleistocene hominins. AB - OBJECTIVE: The purpose of this study is to test the hypothesis that conarticular surfaces areas and curvatures are correlates of mobility at the hominoid talocalcaneal and talonavicular joints. MATERIALS AND METHODS: Articular surface areas and curvatures of the talonavicular, anterior talocalcaneal, and posterior talocalcaneal joints were quantified using a total of 425 three-dimensional surface models of extant hominoid and fossil hominin tali, calcanei, and naviculars. Quadric surface fitting was used to calculate curvatures, pairwise comparisons were used to evaluate statistical differences between taxa, and regression was used to test for the effects of allometry. RESULTS: Pairwise comparisons show that the distributions of values for joint curvature indices follow the predicted arboreal-terrestrial morphocline in hominoid primates with no effect of body mass (PGLS p > 0.05). OH 8 (Homo habilis) and LB 1 (Homo floresiensis) can be accommodated within the range of human variation for the talonavicular joint, whereas MH2 (Australopithecus sediba) falls within the ranges of variation for Pan troglodytes and Gorilla gorilla in measures of posterior talocalcaneal joint congruity. CONCLUSIONS: Joint curvature indices are better discriminators than joint surface area indices, which may reflect a greater contribution of rotation, rather than translation, to joint movement in plantigrade taxa due to discrepancies in conarticular congruence and the "convex concave" rule. The pattern of joint congruence in Au. sediba contributes to other data on the foot and ankle suggesting that the lateral side of the foot was more mobile than the medial side, which is consistent with suggestions of increased medial weight transfer associated with hyperpronation. Am J Phys Anthropol 160:446-457, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27000378 TI - Measurement of Temperature Dependence for Vapor Pressures of Seventeen OH-PBDEs and Eleven MeO-PBDEs by Gas Chromatographic Method. AB - Hydroxylated polybromodiphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) are emerging organic pollutants. Supercooled liquid vapor pressures (p L) and enthalpies of vaporization (?vap H) for seventeen OH PBDEs and eleven MeO-PBDEs were determined by a gas chromatographic technique. p L at 298 K ranged from 0.0173 Pa for 2'-OH-BDE3 to 2.32 * 10(-7) Pa for 3'-OH BDE154 and they are approximately one order of magnitude smaller than those determined for the counterpart polybrominated diphenyl ethers (PBDEs). ?vap H was in the range of 76-121 kJ/mol. The temperature dependence of p L was measured by fitting the experimental data with the log(p L/Pa) = a/(T/K) + b equation, and this corresponds to a 50-265 times higher p L value at 0 versus 30 degrees C. Using fundamental quantum chemical descriptors, two quantitative structure property relationship models (Q cum > 0.935) were developed to estimate p L at any temperature for the additional OH- and MeO-PBDE congeners. PMID- 27000379 TI - Latent Toxicity of Endothall to Anadromous Salmonids During Seawater Challenge. AB - Limited evidence exists on the latent effects of toxicant exposure on the seawater adaptability of anadromous salmon and steelhead. It is unclear whether such an effect exists for the widely used and relatively non-toxic herbicide endothall. Coho salmon, Oncorhynchus kisutch (coho), Chinook salmon, O. tshawytscha (Chinook), and anadromous rainbow trout, O. mykiss (steelhead) were subjected to a 10-day seawater challenge following freshwater treatments [0-12 mg acid equivalent (a.e)./L at 96 h]. Mean survival resulted in 82 % (n = 225), 84 % (n = 133), 90 % (n = 73) and 59 % (n = 147) survival for 0, 3-5, 6-8, and 9-12 mg a.e./L, respectively. Our results indicate a lower toxicity threshold compared with previously reported acute toxicity results, but higher compared with previous seawater challenge studies. We demonstrate the utility of the seawater challenge assay to accurately define toxic effects of pesticides on salmonids with complex life-histories. PMID- 27000380 TI - Validation of an Adapted QuEChERS Method for the Simultaneous Analysis of Polycyclic Aromatic Hydrocarbons, Polychlorinated Biphenyls and Organochlorine Pesticides in Sediment by Gas Chromatography-Mass Spectrometry. AB - A Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method has been adapted and validated for the simultaneous analysis of 16 PAHs, 12 PCBs and 9 OCPs in sediment. The sample preparation was adapted by modifying the nature of the extraction solvent, the extraction technique and the amount of sediment. The analytical performances were evaluated in terms of accuracy, linearity and quantification limits. The method was validated by the analysis of a reference marine sediment material (SRM 1941b). The obtained concentrations are in good agreement with the certified values with recoveries ranging 60 %-103 % for most of PAHs. Acceptable recoveries are obtained for PCBs, ranging 76 %-131 %, and for OCPs ranging 81 %-137 %. The method was applied to the analysis of sediments from the hydro-system Bizerte Lagoon/Ichkeul Lake (Tunisia). The Bizerte lagoon is mainly contaminated by PAHs whereas the Ichkeul lake is mainly by OCPs. PMID- 27000381 TI - Carpal bones of Nacholapithecus kerioi, a Middle Miocene Hominoid From Northern Kenya. AB - OBJECTIVES: The carpal bones of the middle Miocene hominoid Nacholapithecus kerioi are described based on new materials. MATERIALS AND METHODS: The materials comprise a trapezoid, three capitates, two hamates, a centrale, a lunate, a triquetrum, and a pisiform, collected during the 2001 and 2002 field seasons from Nachola, Kenya. We also describe a pisiform recently assigned to the type specimen of N. kerioi, KNM-BG 35250. RESULTS: In the Nacholapithecus wrist, the ulnar styloid process articulates with both the triquetrum and pisiform, and the triquetrum facet on the hamate is relatively proximodistally oriented in dorsal view. The Nacholapithecus capitate possesses a moderate distopalmar hook-like process and separated radial articular facets for the trapezoid and the second metacarpal due to the carpometacarpal ligament attachment that is absent in the Proconsul capitate. DISCUSSION: The carpal anatomy of Nacholapithecus is similar to that of the early Miocene hominoid Proconsul. However, Nacholapithecus wrist anatomy appears to exhibit slightly more emphasized stability. Am J Phys Anthropol 160:469-482, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27000382 TI - [Individualized knee joint endoprosthetics: Patient-specific intrumentation and implant systems]. PMID- 27000383 TI - Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions. AB - Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome even when completely "knocked out," do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations "as a whole" can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. PMID- 27000384 TI - Internal iliac coverage during endovascular repair of abdominal aortic aneurysms is a safe option: A preliminary study. AB - Endovascular aneurysm repairs lacking suitable common iliac artery landing zones occasionally require graft limb extension into the external iliac artery, covering the internal iliac artery origin. The purpose of this study was to assess incidence of type II endoleak following simple coverage of internal iliac artery without embolization during endovascular aneurysm repair. Three hundred eighty-nine endovascular aneurysm repairs performed by a single surgeon (2004 2015) were reviewed. Twenty-seven patients underwent simple internal iliac artery coverage. Type II endoleak was assessed from operative reports and follow-up computed tomography imaging. No patient suffered type II endoleak from a covered internal iliac artery in post-operative computed tomography scans. Follow-up ranged from 0.5 to 9 years. No severe pelvic ischemic complications were observed. In conclusion, for selected cases internal iliac artery coverage without embolization is a safe alternative to embolization in endovascular aneurysm repairs, where the graft must be extended into the external iliac artery. PMID- 27000385 TI - Percutaneous access for endovascular aortic aneurysm repair: A systematic review and meta-analysis. AB - PURPOSE: Our objective was to undertake a comprehensive review of the literature and conduct an analysis of the outcomes of percutaneous endovascular aneurysm repair. METHODS: MEDLINE; EMBASE; CINAHL; CENTRAL; the World Health Organization International Clinical Trials Registry; ClinicalTrials.gov; and ISRCTN Register, and bibliographic reference lists were searched to identify all studies providing comparative outcomes of the percutaneous technique for endovascular aneurysm repair. Success rate and access-related complications were defined as the primary outcome parameters. Combined overall effect sizes were calculated using fixed effect or random effects models. We conducted a network meta-analysis of different techniques for femoral access applying multivariate meta-analysis assuming consistency. FINDINGS: Three randomised controlled trials and 18 observational studies were identified. Percutaneous access was associated with a lower frequency of groin infection (p < 0.0001) and lymphocele (p = 0.007), and a shorter procedure time (p < 0.0001) and hospital length of stay (p = 0.03) compared with open surgical access. Moreover, percutaneous endovascular aneurysm repair did not increase the risk of haematoma, pseudoaneurysm, and arterial thrombosis or dissection. CONCLUSION: Percutaneous access demonstrates advantages over conventional surgical exposure for endovascular aneurysm repair, as indicated by access-related complications and hospital length of stay. Further research is required to define its impact on resource utilization, cost effectiveness and quality of life. PMID- 27000386 TI - Tea tree oil gel for mild to moderate acne; a 12 week uncontrolled, open-label phase II pilot study. AB - BACKGROUND: The efficacy, tolerability and acceptability of a tea tree oil gel (200 mg/g) and face wash (7 mg/g) were evaluated for the treatment of mild to moderate facial acne. METHODS: In this open-label, uncontrolled phase II pilot study, participants applied tea tree oil products to the face twice daily for 12 weeks and were assessed after 4, 8 and 12 weeks. Efficacy was determined from total numbers of facial acne lesions and the investigator global assessment (IGA) score. Tolerability was evaluated by the frequency of adverse events and the mean tolerability score determined at each visit. Product acceptability was assessed via a questionnaire at the end of the study period. RESULTS: Altogether 18 participants were enrolled, of whom 14 completed the study. Mean total lesion counts were 23.7 at baseline, 17.2 at 4, 15.1 at 8 and 10.7 at 12 weeks. Total lesion counts differed significantly over time by repeated measures anova (P < 0.0001). The mean IGA score was 2.4 at baseline, 2.2 at 4, 2.0 at 8 and 1.9 at 12 weeks, which also differed significantly over time (P = 0.0094). No serious adverse events occurred and minor local tolerability events were limited to peeling, dryness and scaling, all of which resolved without intervention. CONCLUSION: This study shows that the use of the tea tree oil products significantly improved mild to moderate acne and that the products were well tolerated. PMID- 27000387 TI - Transforming ICU death into life-radically more. PMID- 27000388 TI - Ten physiologic advances that improved treatment for ARDS. PMID- 27000389 TI - Primary cutaneous nocardiosis caused by Nocardia takedensis with pulmonary dissemination in an immunosuppressed patient. AB - We present a remarkable case of primary cutaneous nocardiosis with pulmonary dissemination due to Nocardia takedensis in a 76-year-old man suffering from marginal zone lymphoma and hypogammaglobulinaemia. We also discuss an alternative treatment to trimethoprim-sulfamethoxazole, which could be contraindicated due to haematological and cutaneous toxicities. This case report is of interest due to the emergence of cutaneous nocardiosis in dermatology. PMID- 27000390 TI - Leiomyosarcoma of the Inferior Vena Cava Confirmed by Aspiration Biopsy With a Catheter During Digital Subtraction Angiography. AB - Leiomyosarcoma of the vascular origin is a rare malignant tumor. It originates from the smooth muscle cells of the media with intra- or extraluminal growth, and in most cases it arises in the inferior vena cava. The diagnosis is often delayed because the clinical symptoms of this disease are often nonspecific. Accurate diagnosis of inferior vena cava leiomyosarcoma (IVCLMS) needs histologic confirmation. We report a case of IVCLMS histologically confirmed by aspiration biopsy with a catheter during digital subtraction angiography presenting with pulmonary emboli in a 65-year-old man. PMID- 27000391 TI - The use of factor Xa inhibitors following opening-wedge high tibial osteotomy for venous thromboembolism prophylaxis. AB - PURPOSE: This study aimed to investigate the incidence of venous thromboembolism (VTE) after medial opening-wedge high tibial osteotomy (OWHTO) and evaluate the efficacy and safety of edoxaban for the prevention of VTE in patients undergoing OWHTO. METHODS: A total of 139 patients with osteoarthritis or osteonecrosis undergoing OWHTO were enrolled in this prospective, randomized study. Four patients were excluded because of preoperatively diagnosed VTE, and 135 patients were divided into two groups-an edoxaban group and a non-edoxaban group-and underwent computed tomography venography on day 7 to check for postoperative VTE. Blood samples were taken on the day before OWHTO and on postoperative days 1, 3, 7, and 14. RESULTS: Treatment with edoxaban reduced the incidence of VTE after OWHTO; however, there was no statistically significant difference between the two groups. No major bleeding was noted in the edoxaban group. There were significant differences in the D-dimer level, prothrombin time, fibrinogen level, and thrombin antithrombin complex levels between the groups. CONCLUSIONS: Edoxaban is an oral, once-daily, selective, direct factor Xa inhibitor that is safe and easy to handle. It may offer a new option for preventing VTE after OWHTO. LEVEL OF EVIDENCE: I. PMID- 27000392 TI - Clinical outcomes after multiligament injured knees: medial versus lateral reconstructions. AB - PURPOSE: The purpose of this study was to analyse the clinical outcomes of multiligament injured knees with respect to the medial collateral ligament and posteromedial corner (PMC) repair or reconstruction versus the posterolateral corner (PLC) reconstruction in patients operated according to a codified surgical protocol. METHODS: Patients were divided into two groups depending on whether PMC or PLC was injured. Cruciate ligaments as well as PMC or PLC were reconstructed/repaired in a one-stage procedure. At minimum of 1-year follow-up, objective and subjective International Knee Documentation Committee (IKDC) forms, Lysholm score and sports activity level were recorded. RESULTS: Thirty-nine patients with a median follow-up time of 57 months (range 12-129) were reviewed. No significant difference was found for functional scores between acute PMC and PLC subgroups. In Group PLC, subjective outcomes tend to be better in the acute than in chronic reconstruction subgroup. CONCLUSIONS: A one-stage protocol with early surgery rather than delayed reconstruction produced better clinical outcomes whatever the injured collateral ligament, medial or lateral. In the future, early and chronic reconstructions as well as each injury pattern should be considered as separate entities in studies on multiple ligament injured knees to reach a better level of evidence. LEVEL OF EVIDENCE: IV. PMID- 27000393 TI - Early osteoarthritis of the knee. AB - There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA. PMID- 27000394 TI - Double-bundle posterior cruciate ligament reconstruction: a biomechanical analysis of simulated early motion and partial and full weightbearing on common reconstruction grafts. AB - PURPOSE: The purpose of this study was to determine the biomechanical effects of simulated immediate motion and weightbearing during rehabilitation on different double-bundle posterior cruciate ligament reconstruction (DB-PCLR) graft options. METHODS: Nine each of commercially prepared (allograft) Achilles tendon allografts, fresh-frozen (autograft) bone-patellar tendon-bone grafts, and fresh frozen quadriceps tendon grafts were paired with commercially prepared anterior tibialis allografts, fresh-frozen semitendinosus grafts, and fresh-frozen semitendinosus grafts, respectively. Graft pairs were loaded to simulate early range of motion on a stationary bicycle, partial weightbearing (30 %), and full weightbearing. RESULTS: Acquired laxity (displacement, mm) between graft pairs was not significantly different during simulated early range of motion. However, during simulated partial weightbearing, the median acquired laxity of the patellar tendon/semitendinosus pair (1.06 mm) was significantly less than that of the quadriceps tendon/semitendinosus (1.50 mm, p = 0.01) and Achilles/anterior tibialis (1.44 mm, p = 0.003) graft pairs. During simulated full weightbearing, significantly less acquired laxity was observed for the patellar tendon/semitendinosus graft pair (2.38 mm) compared to the Achilles/anterior tibialis pair (4.85 mm, p = 0.04), but a significant difference was not observed compared to the QT/semitendinosus graft pair (3.91 mm, n.s.). There were no significant differences in the ultimate loads between any of the graft pairs. CONCLUSIONS: Simulated early range of motion and early partial weightbearing did not result in clinically significant acquired graft laxity in common graft options utilized for DB-PCLR. However, simulated full weightbearing did result in clinically significant acquired graft laxity, and therefore, early rehabilitation protocols should avoid implementing full weightbearing that could contribute to graft failure. PMID- 27000395 TI - Combined reconstruction of the posterior cruciate ligament and medial collateral ligament using a single femoral tunnel. AB - PURPOSE: Lesions of the medial collateral ligament (MCL) are the most common knee ligament injuries, and lesions associated with the anterior cruciate ligament or the posterior cruciate ligament (PCL) in knee dislocations should be reconstructed to prevent failure of the central pivot reconstruction. The purpose of this study was to evaluate the outcomes of combined PCL/MCL reconstruction using a single femoral tunnel with a minimum 2-year follow-up. METHOD: A retrospective study of thirteen patients with combined PCL/MCL injuries was conducted. The patients underwent PCL and MCL reconstruction using an Achilles tendon allograft with a single tunnel in the medial femoral condyle, thereby avoiding tunnel conversion. RESULTS: All patients achieved a range of motion of at least 100 degrees . The mean loss of extension and flexion values compared to the contralateral side was 1 degrees +/- 2 degrees and 9 degrees +/- 10 degrees , respectively. Our results included 26 reconstructions with three (11.5 %) failures, two in the PCL (15.3 %) and one in the MCL (7.6 %), in three different patients. In the final evaluation, the mean IKDC subjective score was 71.63 +/- 16.23, the mean Lysholm score was 80.08 +/- 13.87, and the median Tegner score was 6 (range = 2-7). CONCLUSION: The PCL/MCL reconstruction technique using a single femoral tunnel and an Achilles tendon allograft is safe, avoids the convergence of tunnels in the medial femoral condyle, has excellent results, and is reproducible. LEVEL OF EVIDENCE: IV. PMID- 27000396 TI - Assessment of altered binding specificity of bacteriophage for ciprofloxacin induced antibiotic-resistant Salmonella Typhimurium. AB - This study describes a new effort toward understanding the interaction mechanisms between antibiotic-resistant Salmonella Typhimurium and phages. The antibiotic susceptibility, beta-lactamase activity, bacterial motility, gene expression, and lytic activity were evaluated in ciprofloxacin-induced antibiotic-sensitive Salmonella Typhimurium (ASST(CIP)) and ciprofloxacin-induced antibiotic-resistant S. Typhimurium (ARST(CIP)), which were compared to the wild-type strains (ASST(WT) and ARST(WT)). The MIC values of ampicillin, norfloxacin, chloramphenicol, and tetracycline were significantly increased to > 512, 16, 16, and 256 MUg/ml, respectively, in the ARST(CIP). The lowest and highest extracellular lactamase activities were observed in ASST(WT) (6.85 MUmol/min/ml) and ARST(CIP) (48.83 MUmol/min/ml), respectively. The acrA, lpfE, and hilA genes were significantly upregulated by more than tenfold in both ASST(CIP) and ARST(CIP). The induction of multiple antibiotic resistance resulted from the increased efflux pump activity (AcrAB-TolC). The highest phage adsorption rates were more than 95 % for ASST(WT), ASST(CIP), and ARST(WT), while the lowest adsorption rate was 52 % for ARST(CIP) at 15 min of infection. The least lytic activity of phage was 20 % against the ARST(CIP), followed by ASST(CIP) (30 %). The adsorption rate of phage against ARST(CIP) was 52 % at 15 min of infection, which resulted in the decrease in lytic activity (12 %). Understanding the interaction of phage and bacteria is essential for the practical application of phage to control and detect antibiotic-resistant bacteria. The results provide useful information for understanding the binding specificity of phages for multiple antibiotic-resistant pathogens. PMID- 27000397 TI - The "Naked Truth": Naked Mole-Rats Do Get Cancer. PMID- 27000398 TI - Toward Standardization of Clonality Testing in Veterinary Medicine. PMID- 27000399 TI - Modeling Emergent Diseases: Lessons From Middle East Respiratory Syndrome. PMID- 27000400 TI - Disparities in moderate-to-vigorous physical activity among girls and overweight and obese schoolchildren during school- and out-of-school time. AB - BACKGROUND: Increasing physical activity (PA) during the school day and out-of school time are critical strategies for preventing childhood obesity and improving overall health. The purpose of the present investigation was to examine schoolchildren's volume and type of PA during school-time and out-of-school, compared to national recommendations and differences by sex and weight status. METHODS: This cross-sectional analysis included 517 3(rd)-5(th) grade schoolchildren from 13 New England elementary schools (October 2013-January 2014). Demographics were collected by parent questionnaire. Measured height and weight were used to categorize child weight status. Accelerometer data were collected over 7 days. PA was coded as total activity counts and minutes of sedentary, light, and moderate-to-vigorous physical activity (SED, LPA, MVPA) during 1) school, 2) weekday out-of-school, 3) weekend, and 4) total daily time. Multivariable mixed models were used to examine associations between sex and weight status and total counts, SED, LPA, and MVPA, controlling for demographics, wear-time, and clustering within schools. RESULTS: 453 participants (60.5% girls; mean age 9.1 years; 30.5% overweight/obese) had valid accelerometer wear time (>=3 days, >= 10 h/day). Few children achieved 60 min total daily (15.0%) or school-time (8.0 %) MVPA recommendations. For all time-of-day categories, girls achieved fewer MVPA minutes than boys (p < .0001), and overweight/obese participants achieved fewer MVPA minutes than normal/underweight participants (p = 0.05). Minutes of LPA declined by grade-level (p < .05) and were lower in girls than boys during school-time only (p < .05). CONCLUSION: Disparities in MVPA by sex and weight status across school and out-of-school time highlight the need for programs with equitable reach. PMID- 27000401 TI - Uterine arteriovenous malformation. PMID- 27000402 TI - Effects of a behavioral and health literacy intervention to reduce sugar sweetened beverages: a randomized-controlled trial. AB - BACKGROUND: Despite excessive consumption of sugar-sweetened beverages (SSB), little is known about behavioral interventions to reduce SSB intake among adults, particularly in medically-underserved rural communities. This type 1 effectiveness-implementation hybrid RCT, conducted in 2012-2014, applied the RE AIM framework and was designed to assess the effectiveness of a behavioral intervention targeting SSB consumption (SIPsmartER) when compared to an intervention targeting physical activity (MoveMore) and to determine if health literacy influenced retention, engagement or outcomes. METHODS: Guided by the Theory of Planned Behavior and health literacy strategies, the 6 month multi component intervention for both conditions included three small-group classes, one live teach-back call, and 11 interactive voice response calls. Validated measures were used to assess SSB consumption (primary outcome) and all secondary outcomes including physical activity behaviors, theory-based constructs, quality of life, media literacy, anthropometric, and biological outcomes. RESULTS: Targeting a medically-underserved rural region in southwest Virginia, 1056 adult participants were screened, 620 (59%) eligible, 301 (49%) enrolled and randomized, and 296 included in these 2015 analyses. Participants were 93% Caucasian, 81% female, 31 % <= high-school educated, 43% < $14,999 household income, and 33% low health literate. Retention rates (74%) and program engagement was not statistically different between conditions. Compared to MoveMore, SIPsmartER participants significantly decreased SSB kcals and BMI at 6 months. SIPsmartER participants significantly decreased SSB intake by 227 (95% CI = -326, 127, p < 0.001) kcals/day from baseline to 6 months when compared to the decrease of 53 (95% CI = -88,-17, p < 0.01) kcals/day among MoveMore participants (p < 0.001). SIPsmartER participants decreased BMI by 0.21 (95% CI = -0.35,-0.06; p < 0.01) kg/m(2) from baseline to 6 months when compared to the non-significant 0.10 (95 % CI = -0.23, 0.43; NS) kg/m(2) gain among MoveMore participants (p < 0.05). Significant 0-6 month effects were observed for about half of the theory-based constructs, but for no biological outcomes. Health literacy status did not influence retention rates, engagement or outcomes. CONCLUSIONS: SIPsmartER is an effective intervention to decrease SSB consumption among adults and is promising for translation into practice settings. SIPsmartER also yielded small, yet significant, improvements in BMI. By using health literacy-focused strategies, the intervention was robust in achieving reductions for participants of varying health literacy status. TRIAL REGISTRATION: Clinicaltrials.gov; ID: NCT02193009 . PMID- 27000404 TI - Does clopidogrel plus aspirin really significantly increase the risk of subdural hematoma? PMID- 27000403 TI - The interferon-induced antiviral protein PML (TRIM19) promotes the restriction and transcriptional silencing of lentiviruses in a context-specific, isoform specific fashion. AB - BACKGROUND: The promyelocytic leukemia (PML) protein, a type I interferon (IFN-I) induced gene product and a member of the tripartite motif (TRIM) family, modulates the transcriptional activity of viruses belonging to various families. Whether PML has an impact on the replication of HIV-1 has not been fully addressed, but recent studies point to its possible involvement in the restriction of HIV-1 in human cells and in the maintenance of transcriptional latency in human cell lines in which HIV-1 is constitutively repressed. We investigated further the restriction of HIV-1 and a related lentivirus, SIVmac, by PML in murine cells and in a lymphocytic human cell line. In particular, we studied the relevance of PML to IFN-I-mediated inhibition and the role of individual human isoforms. RESULTS: We demonstrate that both human PML (hPML) and murine PML (mPML) inhibit the early post-entry stages of the replication of HIV-1 and a related lentivirus, SIVmac. In addition, HIV-1 was transcriptionally silenced by mPML and by hPML isoforms I, II, IV and VI in MEFs. This PML-mediated transcriptional repression was attenuated in presence of the histone deacetylase inhibitor SAHA. In contrast, depletion of PML had no effect on HIV-1 gene expression in a human T cell line. PML was found to contribute to the inhibition of HIV-1 by IFN-I. Specifically, IFN-alpha and IFN-beta treatments of MEFs enhanced the PML-dependent inhibition of HIV-1 early replication stages. CONCLUSIONS: We show that PML can inhibit HIV-1 and other lentiviruses as part of the IFN-I-mediated response. The restriction takes place at two distinct steps, i.e. reverse transcription and transcription, and in an isoform-specific, cellular context-specific fashion. Our results support a model in which PML activates innate immune antilentiviral effectors. These data are relevant to the development of latency reversal-inducing pharmacological agents, since PML was previously proposed as a pharmacological target for such inhibitors. This study also has implications for the development of murine models of HIV-1. PMID- 27000405 TI - Prevalence of depressive symptoms in pregnant and postnatal HIV-positive women in Ukraine: a cross-sectional survey. AB - BACKGROUND: Perinatal depression among HIV-positive women has negative implications for HIV-related and other maternal and infant outcomes. The aim of this study was to investigate the burden and correlates of perinatal depression among HIV-positive women in Ukraine, a lower middle income country with one of the largest HIV-positive populations in Europe. METHODS: Cross-sectional surveys nested within the Ukraine European Collaborative Study were conducted of HIV positive women at delivery and between 1 and 12 months postpartum. Depressive symptoms in the previous month were assessed using a self-report screening tool. Other data collected included demographics, antiretroviral therapy (ART)-related self-efficacy, and perceptions of risks/benefits of interventions to prevent mother-to-child transmission (PMTCT). Characteristics of women with and without a positive depression screening test result were compared using Fisher's exact test and chi2 test for categorical variables. RESULTS: A quarter (27% (49/180) antenatally and 25% (57/228) postnatally) of participants screened positive for depressive symptoms. Antenatal risk factors were living alone (58% (7/12) vs. 25% (42/167) p = 0.02), being somewhat/terribly bothered by ART side effects (40% (17/43) vs. 23% (30/129) not /only slightly bothered, p = 0.05) and having lower ART-related self-efficacy (43% (12/28) vs. 23% (25/110) with higher self efficacy, p = 0.05). Postnatally, single mothers were more likely to screen positive (44% (20/45) vs. 21% (18/84) of cohabiting and 19% (19/99) of married women, p < 0.01) as were those unsure of the effectiveness of neonatal prophylaxis (40% (20/45) vs. 18% (28/154) sure of effectiveness, p < 0.01), those worried that neonatal prophylaxis could harm the baby (30% (44/146) vs. 14% (10/73) not worried p < 0.01) and those not confident to ask for help with taking ART (48% (11/23) vs. 27% (10/37) fairly confident and 15 % (4/26) confident that they could do this). Of women who reported wanting help for their depressive symptoms, 82% (37/45) postnatally but only 31% (12/39) antenatally were already accessing peer counselling, treatment adherence programmes, support groups or social services. CONCLUSIONS: A quarter of women screened positive for depression. Results highlight the need for proactive strategies to identify depressive symptoms, and an unmet need for provision of mental health support in the perinatal period for HIV-positive women in Ukraine. PMID- 27000406 TI - Exploring the relationship between socioeconomic factors, method of contraception and unintended pregnancy. AB - BACKGROUND: It is estimated that approximately one-third of pregnancies in Canada are unintended, meaning they were either mistimed (the woman wanted to be pregnant at a different point in time) or undesired (the woman did not want to be pregnant). This study aimed to assess the impact of socioeconomic variables and method of contraception on the decision to either terminate or continue and unintended pregnancy. METHODS: Data were obtained from two contemporaneous studies in Calgary Canada--a cross-sectional study involving women seeking abortion services (n = 577) and a longitudinal cohort study involving women with continuing pregnancies (n = 3552) between 2008 and 2012. Chi square tests and logistic regression were used to examine the association between socioeconomic variables, use of contraception and pregnancy intention. RESULTS: 96.5% of women seeking an abortion and 19.6% of women with ongoing pregnancies reported having an unintended pregnancy. Women with unintended pregnancies were significantly younger (p < 0.001), less educated (p < 0.001), had a lower household income (p < 0.001), were less likely to be in a stable relationship (p < 0.001), and less likely to speak English in the home (p < 0.002). 20.2% reported not using any form of birth control despite their desire to not get pregnant. Among women with unintended pregnancies, the only significant demographic predictor of not using any form of contraception was low educational attainment (OR = 1.7, 95% CI: 1.2 2.4). CONCLUSIONS: Low educational attainment was associated with not using any form of contraception among women with unintended pregnancies. However, as unintended pregnancy occurs across all socio-demographic groups, care providers are encouraged to have an open discussion regarding fertility goals and contraception with all patients and refer them to appropriate resource materials. PMID- 27000407 TI - Direct evidence of two interatomic relaxation mechanisms in argon dimers ionized by electron impact. AB - In weakly bound systems like liquids and clusters electronically excited states can relax in inter-particle reactions via the interplay of electronic and nuclear dynamics. Here we report on the identification of two prominent examples, interatomic Coulombic decay (ICD) and radiative charge transfer (RCT), which are induced in argon dimers by electron collisions. After initial ionization of one dimer constituent ICD and RCT lead to the ionization of its neighbour either by energy transfer to or by electron transfer from the neighbour, respectively. By full quintuple-coincidence measurements, we unambiguously identify ICD and RCT, and trace the relaxation dynamics as function of the collisional excited state energies. Such interatomic processes multiply the number of electrons and shift their energies down to the critical 1-10 eV range, which can efficiently cause chemical degradation of biomolecules. Therefore, the observed relaxation channels might contribute to cause efficient radiation damage in biological systems. PMID- 27000408 TI - Three-Dimensional Accuracy of Virtual Planning and Surgical Navigation for Mandibular Reconstruction With Free Fibula Flap. AB - PURPOSE: Although free fibula flaps are widely used for mandibular reconstruction, their 3-dimensional position is difficult to control during conventional surgery. We aimed to improve this process by using computer-aided design (CAD) and surgical navigation. PATIENTS AND METHODS: We retrospectively reviewed 29 benign tumor patients who underwent primary unilateral mandibular reconstruction with free fibula flap. They were divided into 3 groups: group A, comprising 10 patients, underwent reconstruction based on the surgeon's experience; group B, comprising 7 patients, underwent reconstruction based on CAD; and group C, comprising 12 patients, underwent reconstruction based on CAD and surgical navigation. Condyle and gonion positions and mandibular angles were measured. Operative times were recorded. RESULTS: Among the 17 patients who underwent condylar resection, the average condyle shift was greater in group A than in groups B and C (P < .05). The average gonion shift was greater in groups A and B than in group C (P < .05). The difference between the reconstructed and contralateral mandibular angles was greater in group A than in groups B and C (P < .05). The mean operative time did not differ among the 3 groups. CONCLUSIONS: CAD can guide mandibular angle remodeling and condyle placement. CAD and surgical navigation increase reconstruction accuracy without prolonging operative time. PMID- 27000409 TI - Ultrastructural Analyses of Alveolar Bone in a Patient With Osteomyelitis Secondary to Osteopetrosis: A Review of the Literature. AB - Osteopetrosis is a generic term for generalized sclerotic conditions caused by rare genetic disorders. Decreased osteoclastic activities disturb bone remodeling, resulting in greater mineral density and greater compressive strength; therefore, bone fracture is a major physical symptom of osteopetrosis. Osteomyelitis of the maxilla or mandible is a common and well-documented complication of osteopetrosis. Local infection, such as odontogenic infection, is more likely to lead to osteomyelitis, and treatment strategies can be challenging. However, detailed ultrastructural analyses of bone from patients with osteopetrosis and odontogenic infection are limited. This report describes a case of osteomyelitis of the maxilla and mandible secondary to osteopetrosis in an adult patient and presents ultrastructural data of alveolar bone tissue analyzed by contact microradiography, electron probe microanalysis, and x-ray diffraction. Cases of osteomyelitis of the jaw secondary to osteopetrosis also are reviewed. PMID- 27000410 TI - Central Giant Cell Granuloma of the Mandible Requiring Multiple Treatment Modalities: A Case Report. AB - Central giant cell granuloma (CGCG) is a relatively rare non-neoplastic, intraosseous lesion that exhibits a wide spectrum of clinical behavior, and its management can be particularly challenging even for experienced clinicians. The etiopathogenesis of this disease process remains unclear, although factors such as trauma, inflammatory foci, and a genetic predisposition have been implicated. Although multiple treatment modalities have been used with varying degrees of success, there is no accepted algorithm for therapeutic intervention and little is known about the reasons for success or failure of a given treatment. This article reviews the epidemiology, presentation, classification, and currently used therapies for CGCG while describing the clinical course and successful therapeutic outcome of a young female patient with an aggressive CGCG of the mandible. PMID- 27000411 TI - Management of Self-Harm Injuries in the Maxillofacial Region: A Report of 2 Cases and Review of the Literature. AB - Clinicians face numerous challenges when managing psychiatric patients who self inflict injuries within the maxillofacial region. In addition to a complex clinical examination, there are both surgical and psychiatric factors to consider, such as the risk of damaging vital structures, the exacerbation of the patient's psychiatric status, and the long-term psychosocial and esthetic sequelae. We present 2 cases of adolescents who repeatedly self-inflicted wounds and/or inserted foreign bodies (FBs) into the face, scalp, and neck. The different treatment modalities were based on full evaluation of the patient's clinical, medical, and diagnostic test findings coupled with a psychiatric assessment. The decision for conservative management or surgical intervention was made according to the presence and location of the FBs, degree of hemorrhage, signs and symptoms of infection, and unpleasant scars that could lead to long term psychological impairment. In most cases, the FBs were removed and the wounds were toileted and closed under local or general anesthesia. We advocate a holistic approach via a multidisciplinary team, which is deemed essential to provide the highest quality of care for patients to reduce the risk of further relapses. Lastly, a satisfactory esthetic outcome is always paramount to achieve long-term psychological and physical welfare. PMID- 27000412 TI - A Self-Assembled Metallomacrocycle Singlet Oxygen Sensitizer for Photodynamic Therapy. AB - Although metal-ion-directed self-assembly has been widely used to construct a vast number of macrocycles and cages, it is only recently that the biological properties of these systems have begun to be explored. However, up until now, none of these studies have involved intrinsically photoexcitable self-assembled structures. Herein we report the first metallomacrocycle that functions as an intracellular singlet oxygen sensitizer. Not only does this Ru2 Re2 system possess potent photocytotoxicity at light fluences below those used for current medically employed systems, it offers an entirely new paradigm for the construction of sensitizers for photodynamic therapy. PMID- 27000413 TI - Mutations and deletions of PRC2 in prostate cancer. AB - The Polycomb group of proteins (PcGs) are transcriptional repressor complexes that regulate important biological processes and play critical roles in cancer. Mutating or deleting EZH2 can have both oncogenic and tumor suppressive functions by increasing or decreasing H3K27me3. In contrast, mutations of SUZ12 and EED are reported to have tumor suppressive functions. EZH2 is overexpressed in many cancers, including prostate cancer, which can lead to silencing of tumor suppressors, genes regulating epithelial to mesenchymal transition (EMT), and interferon signaling. In some cases, EZH2 overexpression also leads to its use of non-histone substrates. Lastly, PRC2 associated factors can influence the progression of cancer through progressive mutations or by specific binding to certain target genes. Here, we discuss which mutations and deletions of the PRC2 complex have been detected in different cancers, with a specific focus on the overexpression of EZH2 in prostate cancer. PMID- 27000414 TI - Localised Ag(+) vibrations at the origin of ultralow thermal conductivity in layered thermoelectric AgCrSe2. AB - In materials science, the substructure approach consists in imagining complex materials in which a particular property is associated with a distinct structural feature, so as to combine different chosen physical characteristics, which otherwise have little chance to coexist. Applied to thermoelectric materials, it has been used to achieve simultaneously phonon-glass and electron-crystal properties. Mostly studied for its superionic conductivity, AgCrSe2 is a naturally layered compound, which achieves very low thermal conductivity, ~0.4 W.K(-1).m(-1) at RT (room temperature), and is considered a promising thermoelectric. The Cr atoms of the [CrSe2]infinity layer bear a spin S = 3/2, which orders below TN = 55 K. Here we report low temperature inelastic neutron scattering experiments on AgCrSe2, alongside the magnetic field evolution of its thermal and electrical transport. We observe a very low frequency mode at 3 meV, ascribed to large anharmonic displacements of the Ag(+) ions in the [Ag]infinity layer, and 2D magnetic fluctuations up to 3 TN in the chromium layer. The low thermal conductivity of AgCrSe2 is attributed to acoustic phonon scattering by a regular lattice of Ag(+) oscillating in quasi-2D potential wells. These findings highlight a new way to achieve localised phonon modes in a perfectly crystalline solid. PMID- 27000415 TI - A critical appraisal of transanal minimally invasive surgery (TAMIS) in the treatment of rectal adenoma: a 4-year experience with 51 cases. AB - OBJECTIVE: The aim of this study was to describe feasibility, postoperative morbidity, and histological outcome of transanal minimally-invasive surgery (TAMIS) in patients with rectal adenoma. MATERIAL AND METHODS: All patients who underwent TAMIS at a single institution from December 2011 to December 2015 were retrospectively included in the study. Feasibility was based on tumor size, distance of tumor from the anal verge, operative time, and hospital stay. Thirty day morbidity was defined by the revised Accordion Classification system. Histological outcome included microscopic resection margin status, specimen fragmentation status, and grading of dysplasia in rectal adenoma. RESULTS: A total of 51 patients with rectal adenoma underwent TAMIS. The median tumor diameter was 32 (4-60) mm and the median distance from the anal verge 8 (3-14) cm. Median operative time was 40 (13-116) min and median length of hospital stay was 1 (0-25) days. Overall morbidity was 12% (four grade 1, one grade 2, and one grade 3 complications). 22% had a positive resection margin, whereas 31% had an indefinable resection margin status mostly due to tissue fragmentation. Median follow-up time was 7 (0-40) months. CONCLUSIONS: TAMIS is a challenging surgical technique for treatment of rectal adenoma. Our initial experience among 51 patients resulted in a high proportion of positive resection margins and a high fragmentation rate. The role of TAMIS in the treatment of rectal adenoma is to be defined through comparative studies. PMID- 27000416 TI - Thioredoxin-1 Attenuates Ventricular and Mitochondrial Postischemic Dysfunction in the Stunned Myocardium of Transgenic Mice. AB - AIM: We evaluated the effect of thioredoxin1 (Trx1) system on postischemic ventricular and mitochondrial dysfunction using transgenic mice overexpressing cardiac Trx1 and a dominant negative (DN-Trx1) mutant (C32S/C35S) of Trx1. Langendorff-perfused hearts were subjected to 15 min of ischemia followed by 30 min of reperfusion (R). We measured left ventricular developed pressure (LVDP, mmHg), left ventricular end diastolic pressure (LVEDP, mmHg), and t63 (relaxation index, msec). Mitochondrial respiration, SERCA2a, phospholamban (PLB), and phospholamban phosphorylation (p-PLB) Thr17 expression (Western blot) were also evaluated. RESULTS: At 30 min of reperfusion, Trx1 improved contractile state (LVDP: Trx1: 57.4 +/- 4.9 vs. Wt: 27.1 +/- 6.3 and DN-Trx1: 29.2 +/- 7.1, p < 0.05); decreased myocardial stiffness (LVEDP: Wt: 24.5 +/- 4.8 vs. Trx1: 11.8 +/- 2.9, p < 0.05); and improved the isovolumic relaxation (t63: Wt: 63.3 +/- 3.2 vs. Trx1: 51.4 +/- 1.9, p < 0.05). DN-Trx1 mice aggravated the myocardial stiffness and isovolumic relaxation. Only the expression of p-PLB Thr17 increased at 1.5 min R in Wt and DN-Trx1 groups. At 30 min of reperfusion, state 3 mitochondrial O2 consumption was impaired by 13% in Wt and by 33% in DN-Trx1. ADP/O ratios for Wt and DN-Trx1 decrease by 25% and 28%, respectively; whereas the Trx1 does not change after ischemia and reperfusion (I/R). Interestingly, baseline values of complex I activity were increased in Trx1 mice; they were 24% and 47% higher than in Wt and DN-Trx1 mice, respectively (p < 0.01). INNOVATION AND CONCLUSION: These results strongly suggest that Trx1 ameliorates the myocardial effects of I/R by improving the free radical-mediated damage in cardiac and mitochondrial function, opening the possibility of new therapeutic strategies in coronary artery disease. Antioxid. Redox Signal. 25, 78-88. PMID- 27000417 TI - A case series of peripheral nerve blocks in pediatrics and young adults with skeletal dysplasia. AB - AIM: The purpose of this study was to report our experience with peripheral nerve blockade in pediatric and young adult patients with skeletal dysplasia undergoing knee arthroscopy. BACKGROUND: The incidence of skeletal dysplasia is 1:4000 live births. These patients have biomechanical predispositions to knee joint degeneration, which is often palliated by arthroscopic surgery. Regional anesthesia has been proven to improve the cost and quality of care in adults undergoing arthroscopic knee surgery. METHODS: This was a retrospective case series of patients with skeletal dysplasia undergoing arthroscopic knee surgery from 2012-2014 at a tertiary-care, pediatric hospital. Data pertaining to block effectiveness, technique, adjunct local anesthetic, rates of postoperative nausea/vomiting and admissions, and complications were recorded. RESULTS: Twenty patients with skeletal dysplasia underwent arthroscopic knee surgery during the study period. Ten of these patients received peripheral nerve blockade (12 procedures). All patients received femoral, femoral/sciatic, or femoral/sciatic/obturator blocks. One patient required opioid, constituting a block failure. The same patient required overnight admission for pain control. No patients suffered from PONV. There were no complications associated with any of the blocks performed. CONCLUSIONS: Patients with skeletal dysplasia receiving lower extremity nerve blocks consume minimal opioid and report no major complications. Anesthesiologists should consider this mode of anesthesia in these patients. While no nerve injuries were discovered, further study is necessary to determine whether rates of nerve injury are comparable to that in the general pediatric population. Given the size of the skeletal dysplasia population, this type of study would require close to a decade of metadata from numerous institutions. PMID- 27000418 TI - MicroRNA function in Drosophila melanogaster. AB - Over the last decade, microRNAs have emerged as critical regulators in the expression and function of animal genomes. This review article discusses the relationship between microRNA-mediated regulation and the biology of the fruit fly Drosophila melanogaster. We focus on the roles that microRNAs play in tissue growth, germ cell development, hormone action, and the development and activity of the central nervous system. We also discuss the ways in which microRNAs affect robustness. Many gene regulatory networks are robust; they are relatively insensitive to the precise values of reaction constants and concentrations of molecules acting within the networks. MicroRNAs involved in robustness appear to be nonessential under uniform conditions used in conventional laboratory experiments. However, the robust functions of microRNAs can be revealed when environmental or genetic variation otherwise has an impact on developmental outcomes. PMID- 27000419 TI - Electrically tunable terahertz metamaterials with embedded large-area transparent thin-film transistor arrays. AB - Engineering metamaterials with tunable resonances are of great importance for improving the functionality and flexibility of terahertz (THz) systems. An ongoing challenge in THz science and technology is to create large-area active metamaterials as building blocks to enable efficient and precise control of THz signals. Here, an active metamaterial device based on enhancement-mode transparent amorphous oxide thin-film transistor arrays for THz modulation is demonstrated. Analytical modelling based on full-wave techniques and multipole theory exhibits excellent consistent with the experimental observations and reveals that the intrinsic resonance mode at 0.75 THz is dominated by an electric response. The resonant behavior can be effectively tuned by controlling the channel conductivity through an external bias. Such metal/oxide thin-film transistor based controllable metamaterials are energy saving, low cost, large area and ready for mass-production, which are expected to be widely used in future THz imaging, sensing, communications and other applications. PMID- 27000420 TI - Understanding the Role of Self-Judgment in the Association between Body Dissatisfaction and Quality of Life on Normal-Weight and Overweight Portuguese Women. AB - Literature has demonstrated the negative impact of body image dissatisfaction on women's quality of life. Nonetheless, it has been suggested that the relationship between body dissatisfaction and women's well-being is not linear, and that the processes that mediate this association remain unclear. This study aims to clarify the mediator role of self-judgment in the association between negative body image and psychological quality of life, in two groups: normal-weight and overweight women. This cross-sectional study comprised 200 normal-weight and 92 overweight female college students, aged between 18 and 24 years old, that completed self-report instruments of body dissatisfaction, self-judgment, and quality of life. Results showed that women who presented harsher self-judgment about their perceived failures tended to present lower levels in all quality of life domains. Also, results from mediation analyses indicated the relationship between body dissatisfaction and psychological quality of life was significantly mediated by the mechanisms of self-judgment in the two BMI groups (95% CI [-2.41 to -0.04]; 95% CI [-6.35 to -.89]). This mediational model accounted for 28.3% and 40.7% of psychological quality of life in the normal-weight and overweight groups, respectively. These results suggest that a lower ability to deal with one's failures or inadequacies (e.g., negative evaluation of body image) in a kind and accepting manner may significantly increase the negative impact of body dissatisfaction on one's psychological quality of life. In this way, it seems that, the focus of interventions should go beyond body dissatisfaction and also target the development of adaptive attitudes (opposed to self-critical attitudes) to deal with negative body-related experiences. PMID- 27000421 TI - Evaluation of bacterial contamination of dental unit waterlines and use of a newly designed measurement device to assess retraction of a dental chair unit. AB - INTRODUCTION: Dental unit waterline (DUWL) output water is delivered through instruments of a dental chair unit (DCU) to irrigate and cool teeth. However, these waterlines can be heavily contaminated with bacteria. AIM: The purpose of the present study was to assess retraction and investigate the contamination level and prevalence of bacteria in DUWL output water. METHODS: Fifty-eight DCUs were randomly selected from 30 hospitals in 10 districts of Tianjin, one of the four special municipalities of China. A unique sampling connector was used in place of the dental handpiece to collect water samples. Evaluation of retraction was accomplished using a retraction measurement device designed in accordance with the International Standard ISO 7494-2:2015(E). RESULTS: A total of 263 water samples were collected, and the highest concentration of bacteria [1.8 * 10(6) colony-forming units (CFU)/mL] was found in the handpiece group. Thirty (51.72%) water samples in the handpiece group and 21 (36.21%) in the air/water syringe groups were cultured, yielding colony counts of > 500 CFU/mL. Potential infectious agents, such as Bacillus cereus, Kocuria kristinae and Pseudomonas fluorescens, were isolated from the water samples. Thirty (51.72%) DCUs failed the retraction evaluation. There was a significant, positive correlation (P < 0.05) between the concentration of bacteria in the water sample and the retracted volume. CONCLUSION: It is of paramount importance to increase compliance with the standards for controlling DUWL contamination. Routine microbial monitoring and evaluation of retraction are necessary to provide high-quality water for use in dental treatment. PMID- 27000422 TI - Mechanisms of Biliary Plastic Stent Occlusion and Efforts at Prevention. AB - Biliary stenting via endoscopic retrograde cholangiopancreatography has greatly improved the quality of patient care over the last 30 years. Plastic stent occlusion limits the life span of such stents. Attempts to improve plastic stent patency duration have mostly failed. Metal stents (self-expandable metal stents [SEMSs]) have therefore replaced plastic stents, especially for malignant biliary strictures. SEMS are at least 10 times more expensive than plastic stents. In this focused review, we will discuss basic mechanisms of plastic stent occlusion, along with a systematic summary of previous efforts and related studies to improve stent patency and potential new techniques to overcome existing limitations. PMID- 27000423 TI - Basic Knowledge about Metal Stent Development. AB - Biliary self-expandable metal stents (SEMS), a group of non-vascular stents, have been used in the palliative management of biliary obstruction around the world. However, there are still unmet needs in the clinical application of biliary SEMS. Comprehensive understanding of the SEMS is required to resolve the drawbacks and difficulties of metal stent development. The basic structure of SEMS, including the materials and knitting methods of metal wires, covering materials, and radiopaque markers, are discussed in this review. What we know about the physical and mechanical properties of the SEMS is very important. With an understanding of the basic knowledge of metal stents, hurdles such as stent occlusion, migration, and kinking can be overcome to develop more ideal SEMS. PMID- 27000424 TI - Past, Present, and Future of Gastrointestinal Stents: New Endoscopic Ultrasonography-Guided Metal Stents and Future Developments. AB - Innovations in stent technology and technological advances in endoscopic ultrasonography have led to rapid expansion of their use in the field of gastrointestinal diseases. In particular, endoscopic ultrasonography-guided metal stent insertion has been used for the management of pancreatic fluid collection, bile duct drainage, gallbladder decompression, and gastric bypass. Endoscopic ultrasonography-guided drainage of intra-abdominal fluid collections using a plastic or metal stent is well established. Because of the various limitations such as stent migration, injury and bleeding in the lumen-recently developed, fully covered self-expanding metal stents or lumen-apposing metal stents have been introduced for those fluids management. This article reviews the recent literature on newly developed endoscopic ultrasonography-guided metal stents and the efficacy thereof. PMID- 27000425 TI - Successful Removal of a Large Common Bile Duct Stone by Using Direct Peroral Cholangioscopy and Laser Lithotripsy in a Patient with Severe Kyphosis. AB - A 75-year-old woman with hypertension presented with acute suppurative cholangitis. Chest radiography revealed severe kyphosis. Abdominal computed tomography revealed a large stone impacted in the common bile duct (CBD). The patient underwent emergent endoscopic retrograde cholangiopancreatography, and cholangiography revealed a large stone (7*3 cm) in the CBD that could not be captured using a large basket. We could not use the percutaneous approach for stone fragmentation by using a cholangioscope because of severe degenerative kyphosis. Finally, we performed holmium laser lithotripsy under peroral cholangioscopy by using an ultraslim endoscope, and the large stone in the CBD was successfully fragmented and removed without complications. PMID- 27000426 TI - Successful Endoscopic Ultrasound-Guided Alcohol Ablation of Sporadic Insulinoma Using Three-Dimensional Targeting (with Video). AB - Surgical resection is considered the standard of care in the management of symptomatic insulinoma. In this video, we describe the successful management of a symptomatic insulinoma by using linear array endoscopic ultrasound (EUS)-guided ethanol ablation in a poor surgical candidate. EUS-guided ethanol ablation of insulinoma offers a safer, effective, and less invasive alternative to surgery. PMID- 27000427 TI - Hybrid metamaterial switching for manipulating chirality based on VO2 phase transition. AB - Polarization manipulations of electromagnetic waves can be obtained by chiral and anisotropic metamaterials routinely, but the dynamic and high-efficiency modulations of chiral properties still remain challenging at the terahertz range. Here, we theoretically demonstrate a new scheme for realizing thermal-controlled chirality using a hybrid terahertz metamaterial with embedded vanadium dioxide (VO2) films. The phase transition of VO2 films in 90 degrees twisted E-shaped resonators enables high-efficiency thermal modulation of linear polarization conversion. The asymmetric transmission of linearly polarized wave and circular dichroism simultaneously exhibit a pronounced switching effect dictated by temperature-controlled conductivity of VO2 inclusions. The proposed hybrid metamaterial design opens exciting possibilities to achieve dynamic modulation of terahertz waves and further develop tunable terahertz polarization devices. PMID- 27000429 TI - Revisiting the ichthyodiversity of Java and Bali through DNA barcodes: taxonomic coverage, identification accuracy, cryptic diversity and identification of exotic species. AB - Among the 899 species of freshwater fishes reported from Sundaland biodiversity hotspot, nearly 50% are endemics. The functional integrity of aquatic ecosystems is currently jeopardized by human activities, and landscape conversion led to the decline of fish populations in several part of Sundaland, particularly in Java. The inventory of the Javanese ichthyofauna has been discontinuous, and the taxonomic knowledge is scattered in the literature. This study provides a DNA barcode reference library for the inland fishes of Java and Bali with the aim to streamline the inventory of fishes in this part of Sundaland. Owing to the lack of available checklist for estimating the taxonomic coverage of this study, a checklist was compiled based on online catalogues. A total of 95 sites were visited, and a library including 1046 DNA barcodes for 159 species was assembled. Nearest neighbour distance was 28-fold higher than maximum intraspecific distance on average, and a DNA barcoding gap was observed. The list of species with DNA barcodes displayed large discrepancies with the checklist compiled here as only 36% (i.e. 77 species) and 60% (i.e. 24 species) of the known species were sampled in Java and Bali, respectively. This result was contrasted by a high number of new occurrences and the ceiling of the accumulation curves for both species and genera. These results highlight the poor taxonomic knowledge of this ichthyofauna, and the apparent discrepancy between present and historical occurrence data is to be attributed to species extirpations, synonymy and misidentifications in previous studies. PMID- 27000430 TI - Protons Potentiate GluN1/GluN3A Currents by Attenuating Their Desensitisation. AB - N-methyl-D-aspartate (NMDA) receptors are glutamate- and glycine-gated channels composed of two GluN1 and two GluN2 or/and GluN3 subunits. GluN3A expression is developmentally regulated, and changes in this normal pattern of expression, which occur in several brain disorders, alter synaptic maturation and function by unknown mechanisms. Uniquely within the NMDA receptor family, GluN1/GluN3 receptors produce glycine-gated deeply desensitising currents that are insensitive to glutamate and NMDA; these currents remain poorly characterised and their cellular functions are unknown. Here, we show that extracellular acidification strongly potentiated glycine-gated currents from recombinant GluN1/GluN3A receptors, with half-maximal effect in the physiologic pH range. This was largely due to slower current desensitisation and faster current recovery from desensitisation, and was mediated by residues facing the heterodimer interface of the ligand-binding domain. Consistent with the observed changes in desensitisation kinetics, acidic shifts increased the GluN1/GluN3A equilibrium current and depolarized the membrane in a glycine concentration dependent manner. These results reveal novel modulatory mechanisms for GluN1/GluN3A receptors that further differentiate them from the canonical glutamatergic GluN1/GluN2 receptors and provide a new and potent pharmacologic tool to assist the detection, identification, and the further study of GluN1/GluN3A currents in native preparations. PMID- 27000431 TI - Semiconducting Oligomer Nanoparticles as an Activatable Photoacoustic Probe with Amplified Brightness for In Vivo Imaging of pH. AB - An activatable photoacoustic nanoprobe based on a semiconducting oligomer with amplified brightness and pH-sensing capability is developed by taking advantage of nanodoping to simultaneously create both intraparticle photoinduced electron transfer and intramolecular protonation within a single particle. This organic nanoprobe permits noninvasive real-time ratiometric photoacoustic imaging of pH in tumors in living mice through systemic administration at a relatively low dosage. PMID- 27000432 TI - Problem gambling and the five-factor model of personality: a large population based study. AB - BACKGROUND AND AIMS: Knowledge of the personality characteristics of individuals who develop gambling problems is important for designing targeted prevention efforts. Previous studies of the relationship between the five-factor model of personality and gambling problems were based on small samples not representative of the general population. We estimated differences in neuroticism, extroversion, intellect, agreeableness and conscientiousness between non-problem gamblers and individuals with low, moderate and severe gambling problems. DESIGN: Cross sectional survey. SETTING: Norway. PARTICIPANTS: A total of 10 081 (51.5% female) individuals aged 16-74 years (mean age 46.5 years). MEASURES: The Problem Gambling Severity Index, The Mini-International Personality Item Pool and demographic variables. Differences between groups of gamblers were analysed by ordinary least-squares regression models separately for each personality trait adjusting for gender, age, cohabitation, level of education and work status. FINDINGS: Gamblers with low, moderate and severe levels of gambling problems differed significantly from non-problem gamblers in neuroticism (b = 0.16, 0.34 and 0.66, respectively, all P < 0.001) and conscientiousness (b = -0.13, -0.28 and -0.44, respectively, all P < 0.001). Moderate and severe problem gamblers differed from non-problem gamblers in agreeableness (b = -0.21, P < 0.001 and b = -0.20, P = 0.028, respectively). In addition, gambling problems were much more prevalent among men than women, and more prevalent among those who live alone, individuals without tertiary education and among those who are unemployed or on disability pension. CONCLUSIONS: A higher level of problem gambling severity appears to be associated with higher scores on neuroticism, and with lower scores on conscientiousness and agreeableness in the Mini-International Personality Item Pool. PMID- 27000433 TI - Detection of Recently Discovered Human Polyomaviruses in a Longitudinal Kidney Transplant Cohort. AB - A large number of human polyomaviruses have been discovered in the last 7 years. However, little is known about the clinical impact on vulnerable immunosuppressed patient populations. Blood, urine, and respiratory swabs collected from a prospective, longitudinal adult kidney transplant cohort (n = 167) generally pre operatively, at day 4, months 1, 3, and 6 posttransplant, and at BK viremic episodes within the first year were screened for 12 human polyomaviruses using real-time polymerase chain reaction. Newly discovered polyomaviruses were most commonly detected in the respiratory tract, with persistent shedding seen for up to 6 months posttransplant. Merkel cell polyomavirus was the most common detection, but was not associated with clinical symptoms or subsequent development of skin cancer or other skin abnormalities. In contrast, KI polyomavirus was associated with respiratory disease in a subset of patients. Human polyomavirus 9, Malawi polyomavirus, and human polyomavirus 12 were not detected in any patient samples. PMID- 27000434 TI - Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent. AB - Photoacoustic Tomography (PAT) is a deep-tissue imaging modality, with potential clinical applications in the diagnosis of arthritis, cancer and other disease conditions. Here, we identified Clofazimine (CFZ), a red-pigmented dye and anti inflammatory FDA-approved drug, as a macrophage-targeting photoacoustic (PA) imaging agent. Spectroscopic experiments revealed that CFZ and its various protonated forms yielded optimal PAT signals at wavelengths -450 to 540 nm. CFZ's macrophage-targeting chemical and structural forms were detected with PA microscopy at a high contrast-to-noise ratio (CNR > 22 dB) as well as with macroscopic imaging using synthetic gelatin phantoms. In vivo, natural and synthetic CFZ formulations also demonstrated significant anti-inflammatory activity. Finally, the injection of CFZ was monitored via a real-time ultrasound photoacoustic (US-PA) dual imaging system in a live animal and clinically relevant human hand model. These results demonstrate an anti-inflammatory drug repurposing strategy, while identifying a new PA contrast agent with potential applications in the diagnosis and treatment of arthritis. PMID- 27000435 TI - The red pigment prodigiosin is not an essential virulence factor in entomopathogenic Serratia marcescens. AB - Although pigments produced by pathogenic microbes are generally hypothesized as essential virulence factors, the role of red pigment prodigiosin in the pathogenesis of entomopathogenic Serratia marcescens is not clear. In this study, we analyzed the pathogenicity of different pigmented S. marcescens strains and their non-pigmented mutants in silkworms. Each pigmented strain and the corresponding non-pigmented mutants showed very similar LD50 value (statistically no difference), but caused very different symptom (color of the dead larva). Our results clearly indicated that the red pigment prodigiosin is not an essential virulence factor in entomopathogenic S. marcescens. PMID- 27000436 TI - Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story. AB - Internal tandem duplication within the BCOR gene sequence that encodes the PUFD domain, important in the formation of the non-canonical or variant polycomb repressor complex 1 (v-PRC1), was very recently described in 100% of 20 clear cell sarcomas of kidney (CCSKs). None of those 20 cases bore the YWHAE-NUTM2 transcript, previously described by us in CCSK, and which constitutes the only other recurrent genetic aberration observed in CCSK, prompting consideration that these mutations might be mutually exclusive in CCSK. We analysed a cohort of 159 CCSKs and can now not only confirm that there is indeed mutual exclusivity of these BCOR and YWHAE mutations, but also show that a substantial proportion (in this series 11.8%) of CCSKs bear neither mutation when tested by these assays, raising the possibility of distinct aetiologies for subsets of CCSK. Clinical differences observed between the subsets support this notion. As CCSK may show poor chemo-responsiveness, and current treatment protocols mandate the use of doxorubicin with its associated side-effects, advances in understanding the disease biology with a view to more targeted and personalized treatment is a pressing need. PMID- 27000438 TI - Corrigendum. PMID- 27000439 TI - Cytotoxicity and genotoxicity of a trypanocidal drug quinapyramine sulfate loaded sodium alginate nanoparticles in mammalian cells. AB - We synthesized quinapyramine sulfate loaded-sodium alginate nanoparticles (QS NPs) to reduce undesirable toxic effects of QS against the parasite Trypanosoma evansi, a causative agent of trypanosomosis. To determine the safety of the formulated nanoparticles, biocompatibility of QS-NPs was determined using Vero, Hela cell lines and horse erythrocytes in a dose-dependent manner. Our experiments unveiled a concentration-dependent safety/cytotoxicity (metabolic activity), genotoxicity (DNA damage, chromosomal aberrations), production of reactive oxygen species and hemolysis in QS-NPs treated cells. Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis. However, at very high doses (more than 300 times than the effective doses), we observed more toxicity in QS-NPs treated cells as compared to QS treated cells. QS-NPs were safe at effective trypanocidal doses and even at doses several times higher than the effective dose. PMID- 27000440 TI - Structural elucidation of a pectin from flowers of Lonicera japonica and its antipancreatic cancer activity. AB - To investigate polysaccharide structure from Lonicera japonica, and study its effects on behavior of pancreatic cells, a homogenous polysaccharide, LJ-02-1, was extracted and purified from flowers of L. japonica by DEAE-cellulose and Sephacryl S-200HR column. The molecular weight was estimated to be 54kDa. Monosaccharide composition was determined to be rhamnose, galacturonic acid, galactose and arabinose in the molar ratio of 10.77:7.88:15.45:65.89 by analyzing the PMP derivatives of the monosaccharides from 2M trifluoracetic acid hydrolysis via HPLC. Based on methylation analysis, partial acid hydrolysis, and NMR spectra, the polysaccharide was elucidated to be a rhamnogalacturonan backbone and substituted partly at C-4 of rhamnose. The branches were determined to be T- and 1,4,6-linked beta-d-Galp, T- and 1,5-linked alpha-l-Araf. The polysaccharide might inhibit BxPC-3 and PANC-1 pancreatic cancer cells growth at the concentration of 1mg/mL with inhibitory ratio of 66.7% and 52.1%, respectively. PMID- 27000442 TI - Growing pains. PMID- 27000443 TI - Minority women more likely to develop aggressive breast cancer. PMID- 27000444 TI - Users of smokeless tobacco had higher levels of exposure to nicotine, carcinogens than cigarette smokers. PMID- 27000445 TI - Quality-adjusted time without symptoms or toxicity analysis of pazopanib versus sunitinib in patients with renal cell carcinoma. AB - BACKGROUND: In a phase 3, randomized, open-label trial (Pazopanib versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma, COMPARZ; NCT00720941), pazopanib was found to be noninferior to sunitinib in terms of progression-free survival in patients with metastatic renal cell carcinoma with no prior therapy. Overall treatment differences were evaluated in a post hoc analysis with a quality-adjusted time without symptoms or toxicity (Q-TWiST) methodology. METHODS: Each patient's overall survival was partitioned into 3 mutually exclusive health states: time with grade 3 or 4 toxicity (TOX), time without symptoms of disease or grade 3/4 toxicity of treatment, and time after tumor progression or relapse (REL). The time spent in each state was weighted by a health-state utility associated with that state and summed to calculate the Q-TWiST. A threshold utility analysis was used, and utilities were applied across the range of 0 (similar to death) to 1 (perfect health). RESULTS: A total of 1110 patients were enrolled (557 on pazopanib and 553 on sunitinib). The mean TOX was 31 days (95% confidence interval, 13-48 days) longer for sunitinib versus pazopanib. In the threshold utility analysis, the difference in the Q-TWiST ranged from -11 days (utility for TOX, 1; utility for REL, 0) to 43 days (utility for TOX, 0; utility for REL, 1) in favor of pazopanib across most utility combinations. Differences were significant in less than half of the utility combinations examined, and this typically occurred when the utility for TOX was lower than the utility for REL. CONCLUSIONS: Patients randomized to pazopanib had a slightly longer Q-TWiST in comparison with sunitinib patients, and this was primarily due to the reduced length of TOX. PMID- 27000446 TI - Sequencing bilateral robot-assisted arm therapy and constraint-induced therapy improves reach to press and trunk kinematics in patients with stroke. AB - BACKGROUND: The combination of robot-assisted therapy (RT) and a modified form of constraint-induced therapy (mCIT) shows promise for improving motor function of patients with stroke. However, whether the changes of motor control strategies are concomitant with the improvements in motor function after combination of RT and mCIT (RT + mCIT) is unclear. This study investigated the effects of the sequential combination of RT + mCIT compared with RT alone on the strategies of motor control measured by kinematic analysis and on motor function and daily performance measured by clinical scales. METHODS: The study enrolled 34 patients with chronic stroke. The data were derived from part of a single-blinded randomized controlled trial. Participants in the RT + mCIT and RT groups received 20 therapy sessions (90 to 105 min/day, 5 days for 4 weeks). Patients in the RT + mCIT group received 10 RT sessions for first 2 weeks and 10 mCIT sessions for the next 2 weeks. The Bi-Manu-Track was used in RT sessions to provide bilateral practice of wrist and forearm movements. The primary outcome was kinematic variables in a task of reaching to press a desk bell. Secondary outcomes included scores on the Wolf Motor Function Test, Functional Independence Measure, and Nottingham Extended Activities of Daily Living. All outcome measures were administered before and after intervention. RESULTS: RT + mCIT and RT demonstrated different benefits on motor control strategies. RT + mCIT uniquely improved motor control strategies by reducing shoulder abduction, increasing elbow extension, and decreasing trunk compensatory movement during the reaching task. Motor function and quality of the affected limb was improved, and patients achieved greater independence in instrumental activities of daily living. Force generation at movement initiation was improved in the patients who received RT. CONCLUSION: A combination of RT and mCIT could be an effective approach to improve stroke rehabilitation outcomes, achieving better motor control strategies, motor function, and functional independence of instrumental activities of daily living. TRIAL REGISTRATION: ClinicalTrials.gov. NCT01727648. PMID- 27000447 TI - Two ways to skin a cat: acyldepsipeptides antibiotics can kill bacteria through activation or inhibition of ClpP activity. AB - Infection by Mycobacterium tuberculosis (Mtb) has had a devastating effect on the world population. Acyldepsipeptide antibiotics (ADEPs) are known to kill some bacteria by over activating the bacterial ClpP peptidase. ADEP antibiotics also target Mtb, with the assumption that uncontrolled ADEP-activated proteolysis by ClpP is the common mode of killing. In this issue of Molecular Microbiology, Famulla, et al. now show that ADEP's effectiveness in mycobacteria is likely due to inhibition of ClpP-dependent protease activity rather than activation. This finding of how the same antibiotic can kill bacteria by either inhibiting or activating proteases illustrates the utility of targeting these enzymes for sorely needed new antibiotics. PMID- 27000448 TI - Detection and Molecular Typing of Human Adenoviruses Associated with Respiratory Illnesses in Kerala. AB - Adenoviruses are responsible for approximately 5-10% of acute respiratory infections globally. However, there are a limited number of reports on the types of circulating respiratory human adenoviruses (HAdV) in India. We detected HAdV in the post-mortem specimens of a young child who died as a result of an acute febrile illness. To retrospectively investigate the circulating adenovirus types in the Alappuzha region, samples (n = 235) collected from patients with influenza like illnesses who participated in the influenza surveillance program were screened for HAdV. Fourteen samples were identified as positive for adenovirus by PCR analysis. Adenovirus was isolated from 3 of the 14 PCR-positive samples cultured using HEK-293 cell lines. The viral strains isolated in the study were from children between 6 and 10 years of age. The isolates were identified as adenovirus species C and E. Sequencing analysis of the fiber gene and a BLAST search revealed that 2 of the isolates were type HAdV-C2, and the third isolate was a HAdV-E4. A fiber gene sequence-based phylogenetic tree showed that the HAdV E4 isolate was similar to the Japanese HAdV-E4 strain, whereas the HAdV-C2 isolates formed a distinct cluster. Respiratory infections due to HAdV-E4 are generally observed in adults; this study is the first to demonstrate the involvement of the HAdV-E4 strain in respiratory illnesses in children. PMID- 27000449 TI - Ureaplasma urealyticum: Presence among Sexually Transmitted Diseases. AB - The aim of this study was to detect the presence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Mycoplasma hominis, Trichomonas vaginalis, and Ureaplasma urealyticum in genital specimens of symptomatic patients. This study also examined the role of U. urealyticum in infections of the lower genital tract. Cervical and urethral samples from 96 patients (46 males, 50 females) were tested using the Seeplex((r)) STD6 ACE kit. Consent forms were received and a questionnaire was applied. All statistical analyses were performed using the SPSS statistical software program (version 17.0). Among the samples tested, at least 1 pathogen was detected in 49% of the samples; specifically, the rate of detection of U. urealyticum, M. hominis, C. trachomatis, N. gonorrhoeae, M. genitalium, and T. vaginalis was 29.1%, 10.4%, 8.3%, 7.3%, 6.3%, and 4.2%, respectively. U. urealyticum was detected as the sole pathogen in samples from 10% of female patients and 28.3% of male patients (p = 0.035). U. urealyticum was present in 54.5% (18/33) of samples in which a single pathogen was detected and 71.4% (10/14) of samples in which multiple pathogens were detected. Among men, significant differences in discharge, dysuria, and pruritus were not noted among those with negative results (84.6%, 69.2%, and 38.5%, respectively), among those positive for only U. urealyticum (100%, 66.7%, and 26.7%, respectively), and those positive for N. gonorrhoeae, C. trachomatis, M. genitalium, and T. vaginalis (100%, 93.3%, and 26.7%, respectively). Detection of U. urealyticum, either alone or together with other pathogens, in a symptomatic group of patients is an important finding, particularly in men. PMID- 27000450 TI - High Rates of Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Human Immunodeficiency Virus Infections and Uncommon HBV Genotype/Subtype and HCV Subtype Distributions among Transgender Individuals in Surabaya, Indonesia. AB - Transgender people are at a high risk for sexually transmitted viruses such as hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Moreover, Indonesia has a moderate-to-high rate of HBV infection and rapid epidemic growth of HIV infection; hepatitis C virus (HCV) infection can co-occur with HBV and HIV infections. In this study, 10 of 107 individuals (9.3%) were positive for HBV surface antigen (HBsAg) and/or HBV DNA, whereas 19 of 101 individuals (18.8%) with negative results for HBsAg were positive for HBV core antibody (anti-HBc). Seven of the 107 individuals (6.5%) were anti-HCV positive, and 16 of the 100 tested samples (16.0%) were HIV positive. Genotype and subtype analyses of all 10 HBV DNA (6 HBsAg positive and 4 anti-HBc positive) strains showed that 3 were of the HBV genotype/HBsAg subtype C/adrq+, one was of C/adw2, and 5 were of B/adw2. The HCV subtype distribution showed that 33.3% were of HCV-1b, and 66.7% were of HCV-3k (n = 6). These distributions differed from those found in the general population of Surabaya, Indonesia. Interestingly, HIV subtype analysis showed a high prevalence of HIV, with possible recombinants of CRF01_AE and subtype B. PMID- 27000451 TI - Presepsin Levels of Patients with Crimean-Congo Hemorrhagic Fever. AB - Levels of presepsin (a soluble cluster of differentiation subtype 14 [CD14]) are thought to increase in cases of bacterial infection. CD14 has also been found to play a role in the pathogenesis of various viral diseases. Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral infection. Our study focuses on presepsin levels as a biomarker for CCHF. Serum presepsin levels in a CCHF group (n = 59) and control group (n = 28) were compared. Patients with CCHF were classified according to severity grading score as having mild, moderate, or severe infection and were allocated to corresponding subgroups (groups 1, 2, and 3, respectively). Presepsin levels were measured in serum samples by using a commercial enzyme-linked immunosorbent assay kit. The mean presepsin levels in the CCHF group as a whole and the healthy group were found to be significantly different (1,499.46 +/- 411.96 pg/ml and 430.68 +/- 61.21 pg/ml, respectively). The mean presepsin levels of the CCHF subgroups (1, 2 and 3) and the healthy group were also found to be significantly different (1,204.53 +/- 371.18, 1,464.21 +/- 338.37, 2,007.36 +/- 82.18, and 430.68 +/- 61.21 pg/ml, respectively) (p < 0.05). We also found that as the severity of the disease increased, the presepsin level also increased. We postulate that the presepsin levels could be used as a supportive biomarker for diagnosis and follow-up of the disease. PMID- 27000452 TI - Effects of 1,25-dihydroxyvitamin D3 on Macrophage Cytokine Secretion Stimulated by Porphyromonas gingivalis. AB - Vitamin D is known to be closely associated with periodontitis; however, its exact mechanisms remain to be clarified. The present study aimed to investigate the influence of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on Porphyromonas gingivalis (Pg)-stimulated cytokine production and the involved signaling pathways in macrophages. The main observation was that 1,25(OH)2D3 inhibited Pg induced interleukin (IL)-6 cytokine expression but up-regulated the expression of anti-inflammatory cytokine IL-10. Further analyses showed that 1,25(OH)2D3 decreased p38 mitogen-activated protein kinase (MAPK) and extracellular signal regulated kinase (ERK)1/2 phosphorylation. Inhibited phosphorylation of p38 MAPK and ERK1/2 was associated with decreased level of IL-6 expression, but was not related to increased level of IL-10 expression in macrophages stimulated with Pg. These results suggest that 1,25(OH)2D3 might exert its anti-inflammatory effects on Pg-stimulated macrophages partly through its inhibitory effect on the p38 MAPK and ERK1/2 signaling pathway. PMID- 27000453 TI - Monthly Distribution of Norovirus and Sapovirus Causing Viral Gastroenteritis in Thailand. AB - A total of 1,141 rotavirus-negative stool specimens collected from diarrheic children in 4 distinct regions under sentinel surveillance in Thailand between 2006 and 2008 were examined by reverse-transcription (RT)-PCR for norovirus (NoV) and sapovirus (SaV). Three hundred 3 specimens (26.6%) were positive for NoV, with 34 and 269 belonging to genogroup I (GI) and genogroup II (GII), respectively. Twelve specimens (1.1%) were positive for SaV. Mixed infections were found in 5 specimens: 3 samples indicated the presence of both NoV GI and GII, and 2 samples indicated the presence of both NoV GII and SaV. Analysis of the monthly distribution of NoV and SaV revealed that NoV GII was clustered between September and February, while NoV GI was detected mainly in June and July; SaV was found in May, June, and July. In addition, 3 outbreaks of acute gastroenteritis at 2 junior high schools in Phichit and Bangkok, and at a university in Phitsanulok, Thailand in 2006 were found to have been caused by NoV infection. Sequence analysis of NoVs from sporadic cases and outbreaks showed them to be genotypes GII.4 and GII.6. PMID- 27000454 TI - Saffold Cardiovirus Infection in a 2-Year-Old Boy with Acute Pancreatitis. AB - Saffold cardiovirus (SAFV), first identified in a stool sample in 2007, is thought to be associated with respiratory disease and gastroenteritis. On the other hand, animal experiments suggested that the major viral load, following intraperitoneal inoculation of SAFV in mice, may be detected in the pancreas. However, until now, no cases of SAFV in patients with pancreatitis have been reported. This report presents a unique case in a patient who developed relapsing acute pancreatitis (AP) after hand, foot, and mouth disease, and was suspected to have SAFV-1 infection. A 2-year-old boy was admitted to the hospital because of severe abdominal pain. His serum amylase and lipase levels were elevated. Enhanced computed tomography showed pancreatic swelling and dilation of the main pancreatic duct, leading to a diagnosis of severe AP. The viral genome of SAFV-1 was detected by reverse transcription polymerase chain reaction from fecal samples. Furthermore, the serum neutralization titer for SAFV was elevated during AP, but decreased after 1 year. These findings strongly suggest the patient developed SAFV-1 infection concurrent with AP. Therefore, we propose that a cohort study is required to clarify the relationship between SAFV and AP. PMID- 27000455 TI - Dengue Virus Type 1 Strain Isolated in Indonesia Shows a Close Phylogenetic Relation with the Strains That Caused the Autochthonous Dengue Outbreak in Japan in 2014. PMID- 27000456 TI - Genetic Diversity in Streptococcus dysgalactiae subsp. equisimilis Isolates from Patients with Invasive and Noninvasive Infections in a Japanese University Hospital (2014-2015). AB - Streptococcus dysgalactiae subsp. equisimilis (SDSE) isolates with beta-hemolysis and carbohydrate groups G or C are increasingly recovered from invasive infections in Japan. The aim of this study was to determine the epidemiological characteristics of SDSE isolates circulating locally among patients with invasive and noninvasive infections. We selected groups G/C beta-hemolytic streptococci from a repository at the Clinical Laboratory of Kitasato University Medical Center, from May 2014 through April 2015. Thirteen isolates were identified as SDSE based on the data from API-20 Strep and 16S rRNA sequencing. The samples were from 7 sterile specimens (blood) and 6 non-sterile specimens (pus/sputum/vaginal secretion). Information about the patients with invasive or noninvasive SDSE infections was retrieved from their medical charts. We performed emm genotyping, multilocus sequence typing, a dendrogram analysis of the samples using pulsed-field gel electrophoresis (PFGE), and amplifications of the streptococcal inhibitor of a complement-mediated cell lysis-like gene (sicG) and antimicrobial resistance determinants. We identified 8 different emm genotypes, 8 different sequence types, including 4 novel types, 9 different groups in the PFGE dendrogram, the presence or absence of sicG, and 4 different resistance genotypes. Our observations indicate genetic diversity in SDSE isolates from patients with invasive and noninvasive infections in a Japanese university hospital (2014-2015). PMID- 27000457 TI - Accuracy of LAMP-TB Method for Diagnosing Tuberculosis in Haiti. AB - The procedure of ultra-rapid extraction (PURE) and loop-mediated isothermal amplification for tuberculosis (LAMP-TB) is a simple and rapid manual tuberculosis diagnostic with medium-throughput capability. Because of its simplicity, this method could be useful in resource-limited conditions such as microscopy centers in developing countries. This study was conducted to evaluate the clinical performance of this method in a point-of-care setting. The performance was compared to that of smear microscopy and liquid culture in a hospital laboratory in Haiti, which is considered a representative facility for the implementation of this method. The sensitivity, based on culture-positivity, was 86% (95% confidence interval: 81.3-90.3%) and that based on the smear negative and culture-positive results was 51% (38.7-63.5%). The specificity based on sample negativity for both smear and culture was 98.4% (96.8-99.2). These results are nearly equivalent to those of a clinical study performed in Japan and are comparable with those of other nucleic acid amplification methods. Thus, approximately 18% more tuberculosis patients could be identified by adding the LAMP-TB method to routine smear microscopy in field settings in Haiti. In addition, it is suggested that local technicians could perform LAMP-TB after only short-term training. PMID- 27000458 TI - Epidemiological Characteristics of Sapovirus and Human Astrovirus Detected among Children in Nara Prefecture, Japan, during the 2009/2010-2014/2015 Seasons. AB - The current study elucidated the epidemiological characteristics of sapovirus (SaV) and human astrovirus (HAstV) associated with gastroenteritis among children in regional populations of Nara Prefecture, Japan, during the 2009/2010-2014/2015 seasons. The SaV detection rate was 7.5% (71/948) according to reverse transcription-polymerase chain reaction. A high SaV detection rate of 13.5% was observed among children 4 years of age. The highest SaV detection rate was observed in June (19.2%), followed by July (11.1%). The detected SaV included 7 genotypes: GI.1, GI.2, GII.3, GII.1, GI.3, GII.2, and GV, in order of decreasing prevalence. In comparison, the HAstV detection rate was 4.2% (40/948). The HAstV detection rate among children 4 years of age was 12.2%. The HAstV detection rate was highest in July (13.9%), followed by May (10.5%) and August (6.7%). The detected HAstVs included genotypes 1, 4, 6, and 8. The most prevalent genotype was 1, followed by 4 and 8. This report provides an epidemiological overview of SaV and HAstV infection in Nara Prefecture, Japan. PMID- 27000459 TI - Non Susceptibility of Neonatal and Adult Rats against the Middle East Respiratory Syndrome Coronavirus. AB - The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection. PMID- 27000460 TI - Mycobacterium conceptionense Bloodstream Infection in a Patient with Advanced Gastric Carcinoma. AB - A 65-year-old Japanese male farmer with advanced gastric adenocarcinoma and multiple hepatic metastases was admitted to our hospital. Blood culture results were positive on day 5, and Gram-positive rods were detected. According to the results of Ziehl-Neelsen staining and a cultured colony of this bacterium, we suspected a mycobacterial infection. Suspecting a rapidly growing mycobacterium (RGM), we started multidrug therapy with levofloxacin, clarithromycin, and ethambutol, and the patient recovered from the bloodstream infection. Further gene examination (16S rRNA, hsp65, and sodA) revealed an isolate of Mycobacterium conceptionense. M. conceptionense was first identified as an RGM in 2006. Among previous case reports of M. conceptionense infections, bone and soft tissue infections in hosts with a disorder of the normal structure (e.g., surgical sites) were dominant. We report the characteristics of M. conceptionense infection in this first Japanese case report and a review of the literature. PMID- 27000461 TI - Linezolid as a Potentially Effective Drug for the Treatment of Multidrug Resistant Tuberculosis in Japan. AB - Linezolid (LZD) is classified as a WHO group 5 drug used in the treatment of tuberculosis (TB). Although its efficacy and long-term safety have not yet been established, it is being increasingly used in the treatment of multidrug resistant tuberculosis (MDR-TB) and extensive multidrug-resistant tuberculosis (XDR-TB). The current study is a single-center retrospective clinical analysis of hospitalized M/XDR-TB patients in Fukujuji Hospital involving 26 patients (18 men and 8 women) consecutively treated with combinations of anti-TB drugs including LZD from 2009 to 2015. The sputum culture results were negative after using LZD for an average period of 28.0 +/- 12.0 (average +/- SD) days. LZD was reduced or withdrawn in 11 cases due to adverse effects. Nineteen cases including 3 XDR-TB patients were operated on, and their TB was treated following surgery. The average time from the initiation of LZD therapy to surgery was 87.6 +/- 38.7 (average +/- SD) days. Favorable clinical outcome was maintained in 23 surviving patients, while 3 patients died during treatment because of end stage cancer and aspiration pneumonia. Our study showed that LZD might be clinically effective in the treatment of M/XDR-TB patients in Japan. PMID- 27000462 TI - Epidemiology of Multidrug Resistant Uropathogenic Escherichia coli in Iran: a Systematic Review and Meta-Analysis. AB - Urinary tract infection (UTI) is one of the most common infections in humans. It is primarily caused by uropathogenic Escherichia coli (UPEC), which has a high multidrug resistance (MDR). In consideration of the prevalence of MDR-UPEC strains, the aims of the present study were to systematically review the published data about the prevalence rate of MDR-UPEC from different parts of Iran and to establish the overall relative frequency (RF) of these strains in Iran. We searched several databases including PubMed, ISI Web of Science, Scopus, Google Scholar, IranMedex, and Iranian Scientific Information Database by using the following keywords: "Escherichia coli", "multidrug resistant", "MDR", "urinary tract infections", "UTI", "uropathogenic". and "Iran". Articles or abstracts that reported the prevalence of MDR-UPEC were included in this review. We found 15 articles suitable for inclusion in this study. A pooled estimation of 10,247 UPEC strains showed that 49.4% (95% confidence interval = 48.0-50.7%) of the stranis were MDR positive. The RF of MDR-UPEC in different studies varied from 10.5% to 79.2% in the Kashan and Hamedan provinces, respectively. According to the results of the present study, the RF of MDR-UPEC in Iran is high. Thus, measures should be taken to keep the emergence and transmission of these strains to a minimum. PMID- 27000463 TI - Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise. AB - BACKGROUND: Challenges in the diagnosis and classification of cholangiocarcinoma have made it difficult to quantify the true incidence of this highly aggressive malignancy. METHODS: We analyzed the Surveillance, Epidemiology, and End Results data to assess long-term trends in the age-standardized incidence of intrahepatic and extrahepatic cholangiocarcinoma between 1973 and 2012, correcting for systematic coding errors. Because intrahepatic cholangiocarcinoma (ICC) may frequently be misdiagnosed as cancer of unknown primary (CUP), we also analyzed trends in the incidence of CUP. RESULTS: Between 1973 and 2012, the reported U.S. incidence of ICC increased from 0.44 to 1.18 cases per 100,000, representing an annual percentage change (APC) of 2.30%; this trend has accelerated during the past decade to an APC of 4.36%. The incidence of extrahepatic cholangiocarcinoma increased modestly from 0.95 to 1.02 per 100,000 during the 40-year period (APC, 0.14%). The incidence of CUP with histologic features potentially consistent with cholangiocarcinoma decreased by 51% between 1973 and 2012 (APC, -1.87%), whereas the incidence of CUP with squamous or nonepithelial histologic features increased modestly (APC, 0.42%). CONCLUSION: The recognized incidence of ICC in the U.S. continues to rise, whereas the incidence of ECC is stable. The incidence of CUP has fallen dramatically during the same time period. IMPLICATIONS FOR PRACTICE: Clinical distinctions between cholangiocarcinoma (particularly intrahepatic cholangiocarcinoma [ICC]) and cancer of unknown primary (CUP) can be challenging. Recent discoveries have identified recurrent and potentially targetable genomic abnormalities in ICC, highlighting the importance of improving diagnosis. This study demonstrates that the incidence of ICC is increasing in the U.S., whereas the incidence of extrahepatic cholangiocarcinoma is stable. Concomitantly, the incidence of CUP has declined dramatically, suggesting that improved distinction between ICC and CUP may be a major driver of the increasing recognized incidence of ICC. The increasing incidence of ICC warrants further study of prevention and treatment approaches. PMID- 27000464 TI - The Treatment of Colorectal Cancer During Pregnancy: Cytotoxic Chemotherapy and Targeted Therapy Challenges. AB - : Cancer diagnosed during pregnancy has increased because of delayed child bearing and the known occurrence of age-dependent malignancies. Cases of colorectal cancer (CRC) in pregnancy have recently been reported. With the expected rise in CRC diagnosed in young adults coupled with the current trend of delayed child-bearing, CRC during pregnancy is likely to increase. Treating pregnant women with CRC by using antineoplastics presents a dilemma because there are many unknowns to guide treatment decisions. We review the issues regarding the use of 10 CRC-approved agents in pregnancy. IMPLICATIONS FOR PRACTICE: Colorectal cancer (CRC) in pregnancy is likely to become more common because of the current population trend in delayed child-bearing and the increase in CRC incidence expected among young adults. Practitioners should become familiar with the challenges associated with systemic treatment of a pregnant patient with CRC. This review addresses concerns surrounding the 10 systemic agents approved for CRC to help provide treatment guidance when such a case arises. PMID- 27000465 TI - Safety of an Oral Fixed Combination of Netupitant and Palonosetron (NEPA): Pooled Data From the Phase II/III Clinical Program. AB - BACKGROUND: Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials. MATERIALS AND METHODS: This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures. RESULTS: Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in >=2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare. CONCLUSION: NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity. IMPLICATIONS FOR PRACTICE: Supportive care for cancer should ideally be efficacious, convenient, and well-tolerated. There have been concerns about cardiac safety with current antiemetic prophylactic agents, namely dolasetron and ondansetron. This pooled safety analysis demonstrates that the new oral fixed combination therapy NEPA can be safely added to an antiemetic regimen without increased toxicity. PMID- 27000466 TI - Vaginal colonisation by Mucor circinelloides. Case report with cytopathology, molecular sequencing and epidemiology. PMID- 27000467 TI - Nitrate as a source of nitrite and nitric oxide during exercise hyperemia in rat skeletal muscle. AB - The presence of nitric oxide (NO) synthase enzymes, mainly the NOS1 isoform, in skeletal muscle had been well established; however in the last decade it has been realized that NO may also be produced by reduction of nitrate and tissue nitrite. We have recently shown that rodent skeletal muscle contains unusually high concentrations of nitrate, compared to blood and other tissues, likely produced by oxidation of NOS1-produced NO. In the present study we measured nitrate and nitrite levels in Wistar rat leg tissue before and after acute and chronic exercise of the animals on a treadmill. We found a very large decrease of muscle nitrate levels immediately after exercise accompanied by a transient increase of nitrite levels. A significant decrease in blood nitrate levels accompanied the changes in muscle levels. Using skeletal muscle tissue homogenates we established that xanthine oxidoreductase (XOR) is at least partially responsible for the generation of nitrite and/or NO from nitrate and that this effect is increased by slight lowering of pH and by other processes related to the exercise itself. We hypothesize that the skeletal muscle nitrate reservoir contributes significantly to the generation of nitrite and then, probably via formation of NO, exercise induced functional hyperemia. A model for these metabolic interconversions in mammals is presented. These reactions could explain the muscle-generated vasodilator causing increased blood flow, with induced contraction, exercise, or hypoxia, postulated more than 100 years ago. PMID- 27000468 TI - Occupational exposure and health problems among Polish denturists: a population based study in Lodz province. AB - OBJECTIVE: The aim of this study was to analyse the potential health effects of occupational exposure of denturists in the Lodz province. METHODS: The survey was performed among 103 denturists working in 24 dental laboratories in the Lodz province using the questionnaire prepared by the authors. RESULTS: The most common health problems associated with work (occurring daily or at least once a week) were: back pain (69.8%); chronic fatigue syndrome (61.6%); irritation, itching and rashes on the hands (51.2%); restlessness and aggression (43.0%); and watery and itchy eyes (41.9%). Psychosocial and ergonomic hazards associated with work organisation (72.2%) were the most common work environment factors related to the denturist profession. CONCLUSIONS: Analyses of denturists' occupational exposure in the Lodz province and epidemiological estimates of the health effects suggest the need for preventive measures. PMID- 27000469 TI - Lost in translation? PMID- 27000470 TI - Electroencephalographic findings in panic disorder. AB - Some studies have reported the importance of electroencephalography (EEG) as a method for investigating abnormal parameters in psychiatric disorders. Different findings in time and frequency domain analysis with regard to central nervous system arousal during acute panic states have already been obtained. This study aimed to systematically review the EEG findings in panic disorder (PD), discuss them having a currently accepted neuroanatomical hypothesis for this pathology as a basis, and identify limitations in the selected studies. Literature search was conducted in the databases PubMed and ISI Web of Knowledge, using the keywords electroencephalography and panic disorder; 16 articles were selected. Despite the inconsistency of EEG findings in PD, the major conclusions about the absolute power of alpha and beta bands point to a decreased alpha power, while beta power tends to increase. Different asymmetry patterns were found between studies. Coherence studies pointed to a lower degree of inter-hemispheric functional connectivity at the frontal region and intra-hemispheric at the bilateral temporal region. Studies on possible related events showed changes in memory processing in PD patients when exposed to aversive stimuli. It was noticed that most findings reflect the current neurobiological hypothesis of PD, where inhibitory deficits of the prefrontal cortex related to the modulation of amygdala activity, and the subsequent activation of subcortical regions, may be responsible to trigger anxiety responses. We approached some important issues that need to be considered in further researches, especially the use of different methods for analyzing EEG signals. PMID- 27000471 TI - The broad autism phenotype in parents of individuals with autism: a systematic review of the literature. AB - The broad autism phenotype (BAP) is a milder manifestation of the defining symptoms of the syndrome in individuals without autism. This study conducted a systematic review of studies about behavioral characteristics of interpersonal relationships, communication and rigidity, as well as about three cognitive models, Theory of Mind, central coherence and executive function, in parents of individuals with autism. The indexed databases were LILACS, IBECS, Web of Science, and MEDLINE, and the studies retrieved were published between 1991 and March 2012. Parents of individuals with autism have more difficulties in interpersonal relationships and in pragmatic language use and have more rigidity traits. The inclusions of the cognitive theories in the group of BAP characteristics were inconclusive. PMID- 27000472 TI - Psychological and health comorbidities before and after bariatric surgery: a longitudinal study. AB - INTRODUCTION: Morbid obesity has multiple implications for psychological and physical health. Bariatric surgery has been selected as the treatment of choice for this chronic disease, despite the controversial impact of the surgery on psychosocial health. The objective of this study was to describe candidates for bariatric surgery and analyze changes in weight, psychopathology, personality, and health problems and complaints at 6- and 12- month follow-up assessments. METHODS: Thirty obese patients (20 women and 10 men) with a mean age of 39.17+/ 8.81 years were evaluated in different dimensions before surgery and 6 and 12 months after the procedure. RESULTS: Six and 12 months after bariatric surgery, patients reported significant weight loss and a significant reduction in the number of health problems and complaints. The rates of self-reported psychopathology were low before surgery, and there were no statistically significant changes over time. The conscientiousness, extraversion, and agreeableness dimensions increased, but neuroticism and openness remained unchanged. All changes had a medium effect size. CONCLUSIONS: Our results suggest that patients experience significant health improvements and some positive personality changes after bariatric surgery. Even though these findings underscore the role of bariatric surgery as a relevant treatment for morbid obesity, more in-depth longitudinal studies are needed to elucidate the evolution of patients after the procedure. PMID- 27000473 TI - Translation and cross-cultural adaptation of the Brazilian Portuguese version of the Driving Behavior Survey (DBS). AB - BACKGROUND: Fear of driving has been recognized as a complex diagnostic entity. For this reason, the use of psychometric instruments is fundamental to advancing research in this area. Psychometric instruments are also necessary for clinical care, as they can help conceptualize the disorder and plan adequate treatment. OBJECTIVE: To describe the cross-cultural adaptation of a Brazilian version of the Driving Behavior Survey (DBS). METHODS: The process consisted of: 1) two translations and back-translations carried out by independent evaluators; 2) development of a brief version by four bilingual experts in mental health; 3) experimental application; and 4) investigation of operational equivalence. RESULTS: The adaptation process is described and a final Brazilian version of the DBS is presented. CONCLUSION: A new instrument is now available to assess the driving behaviors of the Brazilian population, facilitating research in this field. PMID- 27000474 TI - Risk behaviors for eating disorder: factors associated in adolescent students. AB - INTRODUCTION: Evidence shows that the prevalence of risk behaviors for eating disorders (RBED) among young people has increased in recent years. Body dissatisfaction, excessive exercise, body composition, economic status, and ethnicity may be risk factors for RBED. OBJECTIVE: To evaluate the association of body dissatisfaction, psychological commitment to exercise, body fat, nutritional status, economic class, and ethnicity with RBED in adolescents. METHOD: This study included 562 boys and girls aged 10 to 15 years. We used the Eating Attitudes Test (EAT-26) to assess RBED. The Body Shape Questionnaire (BSQ) and the Commitment to Exercise Scale (CES) were used to measure body dissatisfaction and commitment to exercise, respectively. Skin fold thickness was measured to classify body fat according to sex. Weight and height were measured to calculate the body mass index (BMI) and classify participants according to nutritional status. The economic class was recorded according to the Brazilian Economic Classification Criterion. A questionnaire was used to record ethnicity, age and sex. Binary logistic regression was used to determine associations between variables. RESULTS: The results showed an association of RBED with body dissatisfaction, CES scores, and economic class among girls (p < 0.05). Among boys, body dissatisfaction, body fat, and nutritional status were associated with RBED (p < 0.05). CONCLUSION: Even though body dissatisfaction had the highest odds ratio, other variables were also associated with RBED. PMID- 27000475 TI - Adaptation of the Barriers to Access to Care Evaluation (BACE) scale to the Brazilian social and cultural context. AB - INTRODUCTION: A significant gap between the number of individuals who need mental health care and the ones who actually have access to it has been consistently demonstrated in studies conducted in different countries. Recognizing the barriers to care and their contributions to delaying or preventing access to mental health services is a key step to improve the management of mental health care. The Barriers to Access to Care Evaluation (BACE) scale is a 30-item self report instrument conceived to evaluate obstacles to proper mental health care. The main constraint in the investigation of these barriers in Brazil is the lack of a reliable instrument to be used in the Brazilian social and cultural context. OBJECTIVE: To describe the translation and adaptation process of the BACE scale to the Brazilian social and cultural context. METHOD: The translation and adaptation process comprised the following steps: 1) translation from English to Brazilian Portuguese by two authors who are Brazilian Portuguese native speakers, one of whom is a psychiatrist; 2) evaluation, comparison and matching of the two preliminary versions by an expert committee; 3) back-translation to English by a sworn translator who is an English native speaker; 4) correction of the back translated version by the authors of the original scale; 5) modifications and final adjustment of the Brazilian Portuguese version. RESULTS AND CONCLUSION: The processes of translation and adaptation described in this study were performed by the authors and resulted in the Brazilian version of a scale to evaluate barriers to access to mental health care. PMID- 27000476 TI - Brazilian version of the Structured Interview for Disorders of Extreme Stress - Revised (SIDES-R): adaptation and validation process. AB - BACKGROUND: Posttraumatic stress disorder (PTSD) contemplates the impact of acute traumatic events, but the literature indicates that this is not true for chronic exposure to stress. In this sense, the category disorders of extreme stress not otherwise specified (DESNOS) has been proposed to characterize the behavior and cognitive alterations derived from exposure to continuous early life stress. The Structured Interview for Disorders of Extreme Stress - Revised (SIDES-R) was developed to investigate and measure DESNOS. Considering the lack of instruments designed to assess DESNOS, especially in Brazil, the aim of this study was to translate, adapt, and validate the contents of SIDES-R to Brazilian Portuguese (SIDES-R-BR). METHOD: The original interview was subjected to translation, back translation, semantic equivalence and conceptual correspondence analyses by naive and specialized judges, respectively, an acceptability trial, and inter-rater validity analysis. RESULTS: The interview underwent semantic and structural adaptations considering the Brazilian culture. The final version, SIDES-R-BR, showed a mean understanding score of 4.98 on a 5-point verbal rating scale, in addition to a kappa coefficient of 0.853. CONCLUSION: SIDES-R-BR may be a useful tool in the investigation of DESNOS and contributes a valuable input to clinical research in Brazil. The availability of the instrument allows to test symptoms with adequate reliability, as verified by the kappa coefficient and translation steps. PMID- 27000477 TI - Neuropsychological assessment before and after radiotherapy in a child with an intracranial tumor: case report. AB - INTRODUCTION: Brain tumors are the most common solid tumors and the second largest group of neoplasms diagnosed in childhood. Treatment includes surgery, radiotherapy, and chemotherapy. However, radiotherapy can cause complications, e.g., cognitive deficits. CASE DESCRIPTION: We describe the case of a child diagnosed with a brain tumor evaluated before and after radiotherapy to investigate cognitive decline after treatment. The results showed a decline in Intelligence Quotient (IQ) scores and reversal of the predominance of verbal and nonverbal skills. After radiotherapy, the subject showed slowness, academic deficits, and difficulties learning new information. COMMENTS: Even though the post-treatment evaluation showed scores compatible with the average, comparison between pre- and post-treatment evaluations demonstrated the impact of radiotherapy on the subject's cognitive profile. These results highlight the importance of evaluating patients who undergo radiotherapy before and after treatment and understanding neuropsychological scores associated with the subjects' complaints. PMID- 27000478 TI - Erratum. PMID- 27000479 TI - Head Transplants and Personal Identity: A Philosophical and Literary Survey. AB - The criterion of personal identity is clearly called into question by the project to perform a human head transplant. Is identity provided by psychological continuity alone, or does it depend on bodily continuity as well? And how do these different perspectives interface with our notion of mind and mind-body relationship? The reader will be provided with a discussion concerning these problems, together with a philosophical and literary survey about the conception of body-mind relationship from the Greek thought to contemporary philosophy. The analysis will conclude with a discussion concerning the possibility to consider the issue of personal identity from a statistic point of view, which privileges the general perception of identity, so as it has been shaped by the cultural trends of the last four centuries. It could hence be argued that personal identity is not something which can be defined once and for all. On the contrary, the general perception of identity is subject to significant alterations resulting from one's cultural environment. However, the cultural environment itself can be changed by particularly notable events, such as, hypothetically, the successful outcome of a human head transplant. PMID- 27000480 TI - Cortical Microvascularization in Moyamoya Disease: Characteristics and the Relations with Surgical Outcomes of Encephaloduroarteriosynangiosis. PMID- 27000481 TI - Get More Acids for More Iron: A New Regulatory Pathway for Iron Homeostasis. PMID- 27000482 TI - Corrigendum. PMID- 27000483 TI - Improvement of the gas cluster ion beam-(GCIB)-based molecular secondary ion mass spectroscopy (SIMS) depth profile with O2(+) cosputtering. AB - Over the last decade, cluster ion beams have displayed their capability to analyze organic materials and biological specimens. Compared with atomic ion beams, cluster ion beams non-linearly enhance the sputter yield, suppress damage accumulation and generate high mass fragments during sputtering. These properties allow successful Secondary Ion Mass Spectroscopy (SIMS) analysis of soft materials beyond the static limit. Because the intensity of high mass molecular ions is intrinsically low, enhancing the intensity of these secondary ions while preserving the sample in its original state is the key to highly sensitive molecular depth profiles. In this work, bulk poly(ethylene terephthalate) (PET) was used as a model material and analyzed using Time-of-Flight SIMS (ToF-SIMS) with a pulsed Bi3(2+) primary ion. The optimized hardware of a 10 kV Ar2500(+) Gas Cluster Ion Beam (GCIB) with a low kinetic energy (200-500 V) oxygen ion (O2(+)) as a cosputter beam was employed for generating depth profiles and for examining the effect of beam parameters. The results were then quantitatively analyzed using an established erosion model. It was found that the ion intensity of the PET monomer ([M + H](+)) and its large molecular fragment ([M - C2H4O + H](+)) steadily declined during single GCIB sputtering, with distortion of the distribution information. However, under an optimized GCIB-O2(+) cosputter, the secondary ion intensity quickly reached a steady state and retained >95% intensity with respect to the pristine surface, although the damage cross-section was larger than that of single GCIB sputtering. This improvement was due to the oxidation of molecules and the formation of -OH groups that serve as proton donors to particles emitted from the surface. As a result, the ionization yield was enhanced and damage to the chemical structure was masked. Although O2(+) is known to alter the chemical structure and cause damage accumulation, the concurrently used GCIB could sufficiently remove the surface layer and allow the damage to be masked by the enhanced ionization yield when the ion-solid interaction volume was kept shallow with a low O2(+) energy. This low O2(+) energy (200 V) cosputtering also produced a smoother surface than a single GCIB. Because the oxidized species were produced by O2(+) and removed by GCIB simultaneously, a sufficiently high O2(+) current density was required to produce adequate enhancements. Therefore, it was found that 10 kV with 2 * 10(-6) A per cm(2) Ar2500(+) and 200 V with 3.2 * 10(-4) A per cm(2) O2(+) produced the best profile. PMID- 27000485 TI - Accelerated Discovery in Photocatalysis using a Mechanism-Based Screening Method. AB - Herein, we report a conceptually novel mechanism-based screening approach to accelerate discovery in photocatalysis. In contrast to most screening methods, which consider reactions as discrete entities, this approach instead focuses on a single constituent mechanistic step of a catalytic reaction. Using luminescence spectroscopy to investigate the key quenching step in photocatalytic reactions, an initial screen of 100 compounds led to the discovery of two promising substrate classes. Moreover, a second, more focused screen provided mechanistic insights useful in developing proof-of-concept reactions. Overall, this fast and straightforward approach both facilitated the discovery and aided the development of new light-promoted reactions and suggests that mechanism-based screening strategies could become useful tools in the hunt for new reactivity. PMID- 27000486 TI - Tumor necrosis factor alpha is a risk factor for infection in peritoneal dialysis patients. AB - BACKGROUND/AIMS: It has been shown that circulating tumor necrosis factor alpha (TNF-alpha) is elevated in end stage renal disease patients; however, the relationship between TNF-alpha and the development of infection in these patients is unknown. In this study, we investigated the association of plasma TNF-alpha and interleukin 6 (IL-6) with infection in peritoneal dialysis (PD) patients. We also evaluated the association of their plasma levels with the production by peripheral blood mononuclear cells (PBMC), and with various clinical parameters. METHODS: We enrolled 32 patients on maintenance PD and 10 healthy controls. Plasma and PBMC were isolated from blood. PBMC were stimulated with lipopolysaccharide in vitro. RESULTS: Mean follow-up duration was 775 days. Six patients developed organ infections (five pneumonia and one liver abscess), and six patients developed PD peritonitis and eight developed exit site infection. Plasma TNF-alpha and IL-6 levels were significantly elevated in organ infections but not in peritonitis or in exit site infection. Plasma TNF-alpha was the only significant risk factor for organ infections and pneumonia in multivariate regression analysis. Patients with high plasma TNF-alpha levels showed a significantly greater cumulative hazard rate for organ infections compared to those with low TNF-alpha levels. Plasma TNF-alpha levels correlated with TNF alpha production by PBMC and showed an inverse association with Kt/V. CONCLUSIONS: This is the first study showing that plasma TNF-alpha is a significant risk factor for infection in PD patients. PMID- 27000487 TI - The effects of symmetry and rigidity on non-adiabatic dynamics in tertiary amines: a time-resolved photoelectron velocity-map imaging study of the cage amine ABCO. AB - The non-adiabatic relaxation dynamics of the tertiary cage-amine azabicyclo[2.2.2]octane (ABCO, also known as quinuclidine) have been investigated following 3p Rydberg excitation at 201 nm using femtosecond time-resolved photoelectron imaging (TRPEI). The aim of the study was to investigate the influence of the rigid and symmetric cage structure found in ABCO on the general non-adiabatic relaxation processes commonly seen in other tertiary aliphatic amines (TAAs). Our data is compared with TRPEI results very recently obtained for several structurally less rigid TAA systems [J. O. F. Thompson et al., Chem. Sci., 2016, 7, 1826-1839] and helps to confirm many of the previously reported findings. The experimental results for ABCO in the short-time (<1 ps) regime strongly support earlier conclusions suggesting that planarization about the N atom is not a prerequisite for efficient 3p-3s internal conversion. Additionally, individual photoelectron peaks within our ABCO data show no temporal shifts in energy. As confirmed by our supporting quantum mechanical calculations, this demonstrates that neither internal conversion within the 3p manifold or significant conformational re-organization are possible in the ABCO system. This result therefore lends strong additional support to the active presence of such dynamical effects in other, less conformationally restricted TAA species, where photoelectron peak shifts are commonly observed. Finally, the extremely long (>1 ns) 3s Rydberg state lifetime seen in ABCO (relative to other TAA systems at similar excitation energies) serves to illustrate the large influence of symmetry and conformational rigidity on intramolecular vibrational redistribution processes previously implicated in mediating this aspect of the overall relaxation dynamics. PMID- 27000488 TI - A 34-Year-Old Male with An Intracranial Mass. PMID- 27000489 TI - A 52-Year-Old Man with Myoclonic Jerks. PMID- 27000492 TI - Erratum. PMID- 27000490 TI - A 14-Year-Old Boy with Left Temporal Mass. PMID- 27000493 TI - Directed Assembly and Development of Material-Free Tissues with Complex Architectures. AB - Material-free tissues are assembled using solely cells. Microstructured hydrogel templates and high content screening allow the formation of centimeter-scale tissues with precise architectures. Similar to developing tissues, these contract autonomously, controllably shift shape, self-scaffold by secreting extracellular matrix, and undergo morphogenesis. PMID- 27000494 TI - Ascaris and hookworm transmission in preschool children in rural Panama: role of subsistence agricultural activities. AB - This longitudinal study explored whether aspects of subsistence agriculture were associated with presence and intensity of Ascaris and hookworm in preschool children in rural Panama. Questionnaires were used to collect data on household socio-demographics, child exposure to agriculture and household agricultural practices. Stool samples were collected from children (6 months-5 years) at 3 time points, with albendazole administered after each to clear infections, resulting in 1 baseline and 2 reinfection measures. A novel Agricultural Activity Index (AAI) was developed using principal components analysis to measure the intensity of household agricultural practices. Zero-inflated negative binomial regression models revealed baseline hookworm egg counts were higher if children went to the agricultural plot and if the plot was smaller. Baseline and reinfection Ascaris egg counts were higher if children went to the plot and households had higher AAI, and higher at baseline if the plot was smaller. Caregiver time in the plot was negatively associated with baseline Ascaris egg counts, but positively associated with baseline hookworm and Ascaris reinfection egg counts. Children who spent more time playing around the home were less likely to be infected with Ascaris at baseline. We conclude that preschool child exposure to subsistence agriculture increased Ascaris and hookworm intensity. PMID- 27000495 TI - Autocrine TGF-beta/ZEB/microRNA-200 signal transduction drives epithelial mesenchymal transition: Kinetic models predict minimal drug dose to inhibit metastasis. AB - The epithelial-mesenchymal transition (EMT) is the crucial step that cancer cells must pass before they can undergo metastasis. The transition requires the activity of complex functional networks that downregulate properties of the epithelial phenotype and upregulate characteristics of the mesenchymal phenotype. The networks frequently include reciprocal repressions between transcription factors (TFs) driving the EMT and microRNAs (miRs) inducing the reverse process, termed mesenchymal-epithelial transition (MET). In this work we develop four kinetic models that are based on experimental data and hypotheses describing how autocrine transforming growth factor-beta (TGF-beta) signal transduction induces and maintains an EMT by upregulating the TFs ZEB1 and ZEB2 which repress the expression of the miR-200b/c family members. After successful model calibration we validate our models by predicting requirements for the maintenance of the mesenchymal steady state which agree with experimental data. Finally, we apply our validated kinetic models for the design of experiments in cancer therapy. We demonstrate how steady state properties of the kinetic models, combined with data from tumor-derived cell lines of individual patients, can predict the minimal amount of an inhibitor to induce a MET. PMID- 27000496 TI - The nutritional status of Methanosarcina acetivorans regulates glycogen metabolism and gluconeogenesis and glycolysis fluxes. AB - Gluconeogenesis is an essential pathway in methanogens because they are unable to use exogenous hexoses as carbon source for cell growth. With the aim of understanding the regulatory mechanisms of central carbon metabolism in Methanosarcina acetivorans, the present study investigated gene expression, the activities and metabolic regulation of key enzymes, metabolite contents and fluxes of gluconeogenesis, as well as glycolysis and glycogen synthesis/degradation pathways. Cells were grown with methanol as a carbon source. Key enzymes were kinetically characterized at physiological pH/temperature. Active consumption of methanol during exponential cell growth correlated with significant methanogenesis, gluconeogenic flux and steady glycogen synthesis. After methanol exhaustion, cells reached the stationary growth phase, which correlated with the rise in glycogen consumption and glycolytic flux, decreased methanogenesis, negligible acetate production and an absence of gluconeogenesis. Elevated activities of carbon monoxide dehydrogenase/acetyl-CoA synthetase complex and pyruvate: ferredoxin oxidoreductase suggested the generation of acetyl-CoA and pyruvate for glycogen synthesis. In the early stationary growth phase, the transcript contents and activities of pyruvate phosphate dikinase, fructose 1,6-bisphosphatase and glycogen synthase decreased, whereas those of glycogen phosphorylase, ADP phosphofructokinase and pyruvate kinase increased. Therefore, glycogen and gluconeogenic metabolites were synthesized when an external carbon source was provided. Once such a carbon source became depleted, glycolysis and methanogenesis fed by glycogen degradation provided the ATP supply. Weak inhibition of key enzymes by metabolites suggested that the pathways evaluated were mainly transcriptionally regulated. Because glycogen metabolism and glycolysis/gluconeogenesis are not present in all methanogens, the overall data suggest that glycogen storage might represent an environmental advantage for methanosarcinales when carbon sources are scarce. Also, the understanding of the central carbohydrate metabolism in methanosarcinales may help to optimize methane production. PMID- 27000499 TI - Efficient and Durable Vaccine against Intimin beta of Diarrheagenic E. Coli Induced by Clay Nanoparticles. AB - Improved strategies are urgently required to control infections with enterohemorrhagic Escherichia coli and enteropathogenic E. coli, two dominant zoonotic enteric pathogens responsible for a wide spectrum of illnesses as well as deaths of human being, with tremendous financial cost worldwide. The present study investigates the capacity of two clay nanoparticles (NPs) with opposite surface charges, namely synthetic layered double hydroxide (LDH) and hectorite (HEC) NPs as adjuvants to promote strong immune responses against the infections. Here both LDH and HEC NPs are showed to be able to carry an appreciable amount of Intimin beta (1.1 and 4.4 mg per mg clay nanomaterials, respectively) and significantly facilitate antigen uptake by antigen-presenting cells. Remarkably, these clay NPs induce strong antibody and cell-mediated immune responses, which are much higher than that by the potent adjuvant, QuilA. Furthermore, these strong immune responses are well maintained for at least four months in the mouse model, during which there are no changes in histopathology of the animal organs. Collectively these data demonstrate the suitability of LDH and HEC NPs as useful adjuvants in new-generation vaccine formulations to control various infectious diseases. PMID- 27000501 TI - THE LONG-TERM EFFICACY OF ACUTE-PHASE PSYCHOTHERAPY FOR DEPRESSION: A META ANALYSIS OF RANDOMIZED TRIALS. AB - BACKGROUND: Understanding the effectiveness of treatment for depression in both the short term and long term is essential for clinical decision making. The present meta-analysis examined treatment effects on depression and quality of life in acute-phase psychotherapeutic interventions compared to no treatment control groups for adult depression at 6 months or longer postrandomization. METHODS: A systematic literature search resulted in 44 randomized controlled trials with 6,096 participants. Acute-phase psychotherapy was compared to control groups at 6-month or longer postrandomization. Odds ratios of a positive outcome were calculated. RESULTS: Psychotherapy outperformed control groups at 6 months or longer postrandomization (OR = 1.92, 95% CI: 1.60-2.31, P < .001). Heterogeneity was moderate (I2: 65, 95% CI: 53-74, P < .001). However, effects significantly decreased with longer follow-up periods. Additionally, a small positive effect of psychotherapy was observed for quality of life, while similar effects were obtained in separate analyses of each type of psychotherapy, with the exception of nondirective supportive therapy. Studies that provided booster sessions had better treatment results compared with studies that did not provide any further sessions. Finally, we found that trials on psychotherapy aimed at major depressive disorder (MDD) had better outcomes than those that were aimed at elevated depressive symptoms. CONCLUSIONS: There is substantial evidence that acute-phase psychotherapy results in a better treatment effects on depression and quality of life in the long term for adult patients with depression. PMID- 27000503 TI - Dose Tolerance for Stereotactic Body Radiation Therapy. PMID- 27000502 TI - The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation. AB - Genes related to the parathyroid hormone (PTH) influence cutaneous immune defense and development, but the full functions of the PTH family in cutaneous biology remain incompletely understood. In this study, we examined the expression and potential functions of the PTH second receptor (PTH2R) and its ligand, the tuberoinfundibular peptide of 39 residues (TIP39), in the skin. TIP39 and PTH2R mRNA and protein were detectable in both human and mouse skin, and in cultured keratinocytes and adipocytes. TIP39 was observed in the basal layer of human skin, whereas PTH2R was detected in the spinous to granular layer. The subcellular localization of TIP39 in keratinocytes changed during calcium-induced differentiation and shifted to colocalize with PTH2R at the membrane. The addition of recombinant TIP39 to normal human keratinocytes in culture induced an increase in intercellular calcium and triggered aspects of terminal differentiation including decreased keratin-14 and increased involucrin expression. Consistent with these observations, PTH2R(-/-) mice were observed to have increased epidermal thickness. In summary, identification of TIP39 and its receptor in the epidermis reveals an additional PTH family member that is expressed in the skin and may influence keratinocyte function. PMID- 27000504 TI - Introduction and Clinical Overview of the DVH Risk Map. AB - Radiation oncologists need reliable estimates of risk for various fractionation schemes for all critical anatomical structures throughout the body, in a clinically convenient format. Reliable estimation theory can become fairly complex, however, and estimates of risk continue to evolve as the literature matures. To navigate through this efficiently, a dose-volume histogram (DVH) Risk Map was created, which provides a comparison of radiation tolerance limits as a function of dose, fractionation, volume, and risk level. The graphical portion of the DVH Risk Map helps clinicians to easily visualize the trends, whereas the tabular portion provides quantitative precision for clinical implementation. The DVH Risk Map for rib tolerance from stereotactic ablative body radiotherapy (SABR) and stereotactic body radiation therapy (SBRT) is used as an example in this overview; the 5% and 50% risk levels for 1-5 fractions for 5 different volumes are given. Other articles throughout this issue of Seminars in Radiation Oncology present analysis of new clinical datasets including the DVH Risk Maps for other anatomical structures throughout the body. PMID- 27000505 TI - Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery. AB - Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using alpha/beta = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus. PMID- 27000506 TI - Multisession Radiosurgery for Hearing Preservation. AB - Clinically relevant dose-tolerance limits with reliable estimates of risk in 1-5 fractions for cochlea are still unknown. Timmerman's limits from the October 2008 issue of Seminars in Radiation Oncology have served as the basis for clinical practice, augmented by updated constraints in TG-101 and QUANTEC, but the corresponding estimates of risk have not yet been well-reported. A total of 37 acoustic neuroma CyberKnife cases from Medstar Georgetown University Hospital treated in 3 or 5 fractions were combined with single-fraction Gamma Knife data from the 69 cases in Timmer 2009 to form an aggregate dataset of 106 cochlea cases treated in 1-5 fractions. Probit dose-response modeling was performed in the DVH Evaluator software to estimate normal tissue complication probability. QUANTEC recommends keeping single-fraction maximum dose to the cochlea less than 14Gy to maintain less than 25% risk of serviceable hearing loss, and our 17.9% risk estimate for 14Gy in 1 fraction is within their predicted range. In 5 fractions, our estimate of the Timmerman 27.5Gy maximum cochlea dose limit was 17.4%. For cases in which lower risk is required, the Timmerman 12Gy in 1 fraction and the TG-101 limit of 25Gy in 5 fractions had an estimated risk level of 11.8% and 13.8%, respectively. High-risk and low-risk dose tolerance with risk estimates in 1-5 fractions are all presented. PMID- 27000507 TI - Toxicities Following Stereotactic Ablative Radiotherapy Treatment of Locally Recurrent and Previously Irradiated Head and Neck Squamous Cell Carcinoma. AB - Stereotactic ablative radiotherapy (SABR) with concomitant cetuximab is an effective treatment option for previously irradiated, locally recurrent squamous cell carcinoma of the head and neck. Its local control and overall survival are similar to those of other available treatment options. Each retreatment depends heavily on the prior treatment and every patient is a special case. Based on the experience of our institution and previously published studies, for patients who receive concomitant cetuximab with a median prior radiation therapy dose of 70Gy, we recommend a total dose of 40-44Gy delivered in 5 fractions on alternating days over 1-2 weeks. However, Grade 2 or 3 toxicities are not uncommon. Therefore, in this review, we also report a pilot study that applies a normal tissue complication probability dose-response model to estimate the probability of toxicities in locally recurrent squamous cell carcinoma of the head and neck reirradiated with SABR. Although this dose-response model includes concurrent targeted therapy and no comparable model yet exists for SABR without it, complication rates without concurrent biological therapy or chemotherapy should be no higher than those described here. PMID- 27000508 TI - Esophageal Dose Tolerance in Patients Treated With Stereotactic Body Radiation Therapy. AB - Mediastinal critical structures such as trachea, bronchus, esophagus, and heart are among the dose-limiting factors for stereotactic body radiation therapy (SBRT) to central lung lesions. The purpose of this study was to characterize the risk of esophagitis for patients treated with SBRT and to develop a statistical dose-response model to assess the equivalent uniform dose, D10%, D5cc, D1cc, and Dmax, to the esophagus and the risk of toxicity. Toxicity outcomes of a dose escalation study of 56 patients who had taken CyberKnife treatment from 45-60Gy in 3-7 fractions at the Erasmus MC-Daniel den Hoed Cancer Center were utilized to create the dose-response model for esophagus. A total of 5 grade 2 esophageal complications were reported (Common Terminology Criteria for Adverse Events version 3.0); 4 complications were early effects and 1 complication was a late effect. All analyses were performed in terms of 5-fraction equivalent dosing. According to our study, D1cc at a dose of 32.9Gy and Dmax dose of 43.4Gy corresponded to a complication probability of 50% for grade 2 toxicity. In this series of 58 CyberKnife mediastinal lung cases, no grade 3 or higher esophageal toxicity occurred. Our estimates of esophageal toxicity are compared with the data in the literature. Further research needs to be performed to establish more reliable dose limits as longer follow-up and toxicity outcomes are reported in patients treated with SBRT for central lung lesions. PMID- 27000509 TI - Dose-Response Model for Chest Wall Tolerance of Stereotactic Body Radiation Therapy. AB - Many recent studies have described rib fractures and chest wall pain following stereotactic body radiation therapy (SBRT). Although these toxicities generally are not life-threatening, the chest wall and ribs are considered dose-limiting tissues because of the potential effect on patients' quality of life. Few studies have reported dose-response models that can provide quantitative estimates of risk as a function of dose and volume. Notably, Memorial Sloan Kettering Cancer Center (Mutter et al(8)) analyzed grade 2 or higher chest wall toxicity in a cohort of 126 patients treated with linear accelerator-based SBRT; the authors provided detailed dose-volume histogram (DVH) data to allow for pooled analyses. We pooled these 126 patients with an additional 44 patients treated with CyberKnife at the Erlanger Medical Center to create an updated dose-response model for chest wall tolerance. In the aggregate analysis, the 10% risk level for grade 2 or higher complications for D70cc was 16.2Gy in 4 fractions, and the 50% risk level was D70cc = 65.1Gy in 4 fractions. For D2cc, the 10% and 50% risk levels in 4 fractions were 43.0Gy and 87.9Gy, respectively. These dose-tolerance limits may help quantify chest wall toxicity risks. Further research continues to determine more accurate estimates of grade 3 risk levels. PMID- 27000510 TI - Validity of Current Stereotactic Body Radiation Therapy Dose Constraints for Aorta and Major Vessels. AB - Understanding dose constraints for critical structures in stereotactic body radiation therapy (SBRT) is essential to generate a plan for optimal efficacy and safety. Published dose constraints are derived by a variety of methods, including crude statistics, actuarial analysis, modeling, and simple biologically effective dose (BED) conversion. Many dose constraints reported in the literature are not consistent with each other, secondary to differences in clinical and dosimetric parameters. Application of a dose constraint without discriminating the variation of all the factors involved may result in suboptimal treatment. This issue of Seminars in Radiation Oncology validates dose tolerance limits for 10 critical anatomic structures based on dose response modeling of clinical outcomes data to include detailed dose-volume metrics. This article presents a logistic dose response model for aorta and major vessels based on 238 cases from the literature in addition to 387 cases from MD Anderson Cancer Center at Cooper University Hospital, for a total of 625 cases. The Radiation Therapy Oncology Group (RTOG) 0813 dose-tolerance limit of Dmax = 52.5Gy in 5 fractions was found to have a 1.2% risk of grade 3-5 toxicity, and the Timmerman 2008 limit of Dmax = 45Gy in 3 fractions had 2.3% risk. From the model, the 1% and 2% risk levels for D4cc, D1cc, and D0.5cc are also provided in 1-5 fractions, in the form of a dose-volume histogram (DVH) Risk Map. PMID- 27000511 TI - Dose and Volume of the Irradiated Main Bronchi and Related Side Effects in the Treatment of Central Lung Tumors With Stereotactic Radiotherapy. AB - High radiation dose to the main bronchi can result in stenosis, occlusion or fistula formation, and death. Only 8 articles have reported side effects to the main bronchi from stereotactic body radiation therapy (SBRT), mostly with only one symptomatic complication per article. Therefore, we calculated the dose to the bronchial structures, such as trachea; mainstem bronchi; intermediate bronchus; upper-, middle-, and lower-lobe bronchus; and the segmental bronchi in 134 patients with central tumors and calculated the normal tissue complication probability (NTCP) for each of these structures, with toxicity determination based upon computed tomography imaging. No side effects were found in the trachea, and only stenosis occurred in the main bronchus and bronchus intermedius. Higher grades of side effects, such as occlusion and atelectasis, were only seen in the upper-, middle-, and lower bronchi and the segmental bronchi. When 0.5cc of a segmental bronchi was irradiated to 50Gy in 5 fractions, it was about 50% likely to be occluded radiographically. For grade 1 radiographically evident side effects, the 50% risk level for a 5-fraction Dmax was 55Gy for mid-bronchi and 65Gy for mainstem bronchi. To assure the relationship between clinical toxicity and side effects to the bronchi, further investigation is needed. PMID- 27000512 TI - Dose-Volume Histogram Analysis of Stereotactic Body Radiotherapy Treatment of Pancreatic Cancer: A Focus on Duodenal Dose Constraints. AB - Pancreatic carcinoma is an aggressive disease and radiotherapy treatment delivery to the primary tumor is constrained by the anatomical close location of the duodenum, stomach, and small bowel. Duodenal dose tolerance for radiosurgery in 2 5 fractions has been largely unknown. The literature was surveyed for quantitative models of risk in 1-5 fractions and we analyzed our own patient population of 44 patients with unresectable pancreatic tumors who received 3 or 5 fractions of stereotactic body radiotherapy (SBRT) between March 2009 and March 2013. A logistic model was constructed in the dose-volume histogram (DVH) Evaluator software for the duodenal D50%, D30cc, D5cc, D1cc, and maximum point dose D0.035cc. Dose tolerance limits from the literature were overlaid onto the clinical duodenal data in the form of a DVH Risk Map, with risk levels of the published limits estimated from the model of clinical data. In 3 fractions, Kopek 2010 found a statistically significant difference in D1cc of patients with no common terminology criteria for adverse events (CTCAE) v3 grade 2 or higher duodenal complications (mean D1cc = 25.3Gy) as compared with patients with grade 2 or higher toxicity (mean D1cc = 37.4Gy). From the logistic model of our duodenal data in 3 fractions, D1cc = 25.3Gy had 4.7% risk of grade 3-4 hemorrhage or stricture and D1cc = 37.4Gy had 20% risk. The 10% risk level was D1cc = 31.4Gy and we were able to keep duodenum dose for all our patients later this level. PMID- 27000513 TI - Small Bowel Dose Tolerance for Stereotactic Body Radiation Therapy. AB - Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation. PMID- 27000514 TI - Estimated Risk Level of Unified Stereotactic Body Radiation Therapy Dose Tolerance Limits for Spinal Cord. AB - A literature review of more than 200 stereotactic body radiation therapy spine articles from the past 20 years found only a single article that provided dose volume data and outcomes for each spinal cord of a clinical dataset: the Gibbs 2007 article (Gibbs et al, 2007(1)), which essentially contains the first 100 stereotactic body radiation therapy (SBRT) spine treatments from Stanford University Medical Center. The dataset is modeled and compared in detail to the rest of the literature review, which found 59 dose tolerance limits for the spinal cord in 1-5 fractions. We partitioned these limits into a unified format of high-risk and low-risk dose tolerance limits. To estimate the corresponding risk level of each limit we used the Gibbs 2007 clinical spinal cord dose-volume data for 102 spinal metastases in 74 patients treated by spinal radiosurgery. In all, 50 of the patients were previously irradiated to a median dose of 40Gy in 2 3Gy fractions and 3 patients developed treatment-related myelopathy. These dose volume data were digitized into the dose-volume histogram (DVH) Evaluator software tool where parameters of the probit dose-response model were fitted using the maximum likelihood approach (Jackson et al, 1995(3)). Based on this limited dataset, for de novo cases the unified low-risk dose tolerance limits yielded an estimated risk of spinal cord injury of <=1% in 1-5 fractions, and the high-risk limits yielded an estimated risk of <=3%. The QUANTEC Dmax limits of 13Gy in a single fraction and 20Gy in 3 fractions had less than 1% risk estimated from this dataset, so we consider these among the low-risk limits. In the previously irradiated cohort, the estimated risk levels for 10 and 14Gy maximum cord dose limits in 5 fractions are 0.4% and 0.6%, respectively. Longer follow-up and more patients are required to improve the risk estimates and provide more complete validation. PMID- 27000515 TI - A systematic review of the risks factors associated with the onset and natural progression of epilepsy. AB - Epilepsy is a neurological condition that affects more than 50 million individuals worldwide. It presents as unpredictable, temporary and recurrent seizures often having negative physical, psychological and social consequences. To inform disease prevention and management strategies, a comprehensive systematic review of the literature on risk factors for the onset and natural progression of epilepsy was conducted. Computerized bibliographic databases for systematic reviews, meta-analyses, observational studies and genetic association studies published between 1990 and 2013 describing etiological risk factors for epilepsy was searched. The quality of systematic reviews was validated using the AMSTAR tool and articles were reviewed by two referees. A total of 16,958 articles went through stage one review of abstracts and titles. A total of 76 articles on genetic and non-genetic risk factors for the onset and progression of epilepsy met the eligibility criteria for data extraction. Dozens of risk factors were significantly associated with onset of epilepsy. Inconsistent levels of evidence for risk of onset included family history of epilepsy, history of febrile seizures, alcohol consumption, CNS and other infections, brain trauma, head injury, perinatal stroke, preterm birth and three genetic markers. Limited evidence showed that symptomatic epilepsy, focal seizures/syndromes, slow waves on EEG, higher seizure frequency, high stress or anxiety, and lack of sleep decreased the odds of seizure remission. High quality studies were rare and while a large body of work exists, relatively few systematic reviews were found. PMID- 27000516 TI - A systematic review of the risks factors associated with the onset and natural progression of hydrocephalus. AB - The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of hydrocephalus, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Evidence for risk factors was limited for both onset and progression. Two meta analyses that examined a risk factor for onset met the inclusion criteria. One found a significant protective effect of prenatal vitamins among case control studies, but not cohort/randomized controlled trials (RCTs). The second found maternal obesity to be a significant risk factor for congenital hydrocephalus. Significant risk factors among 25 observational studies included: biological (multiple births, maternal parity, common cold with fever, maternal thyroid disease, family history, preterm birth, hypertension, ischemic heart disease, ischemic ECG changes, higher cerebrospinal fluid protein concentration following vestibular schwannoma); lifestyle (maternal obesity, high-density lipoprotein (HDL) cholesterol, maternal diabetes, maternal age), healthcare-related (caesarean section, interhospital transfer, drainage duration following subarachnoid hemorrhage, proximity to midline for craniectomy following traumatic brain injury); pharmaceutical (prenatal exposure to: tribenoside, metronidazole, anesthesia, opioids); and environmental (altitude, paternal occupation). Three studies reported on genetic risk factors: no significant associations were found. There are major gaps in the literature with respect to risk factors for the natural progression of hydrocephalus. Only two observational studies were included and three factors reported. Many risk factors for the onset of hydrocephalus have been studied; for most, evidence remains limited or inconclusive. More work is needed to confirm any causal associations and better inform policy. PMID- 27000517 TI - Mechanisms of resistance to insecticides targeting RDL GABA receptors in planthoppers. AB - Lindane and cyclodienes, such as dieldrin and alpha-endosulfan, represent the first generation of noncompetitive antagonists (NCAs) against the insect RDL GABA receptor. It has been reported that A2'S and A2'G mutations in the membrane spanning region M2 of the RDL GABA receptor confer resistance to lindane and cyclodienes. Fipronil is a second-generation NCA, but A2'S and A2'G mutations provide a low level of cross-resistance to fipronil. Moreover, a novel A2'N mutation that confers fipronil resistance was found in M2 of the RDL GABA receptors from fipronil-resistant planthoppers in the heterozygous state. Thus, problems are being caused by a worldwide appearance of cyclodiene-resistant pests. And attention must be paid to development of fipronil-resistant planthoppers, such as Sogatella furcifera and Laodelphax striatellus in Japan. PMID- 27000518 TI - A systematic review of the risks factors associated with the onset and natural progression of spina bifida. AB - The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of spina bifida, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Searches of several health literature databases from inception to February 2013 were conducted by a health sciences librarian. A total of three meta-analyses that studied a risk factor for the onset of spina bifida were included. Pooled results showed that paternal exposure to Agent Orange (RR=2.02; 95% CI 1.48-2.74) and maternal obesity prior to pregnancy (OR=2.24; 95% CI 1.86-2.74) each increased the risk of having a child with spina bifida. Paternal exposure to organic solvents was also close to the limit of significance (OR=1.59; 95% CI 0.99-2.56). A total of 63 observational studies, encompassing hundreds of potential risk factors, were included for risk factors for the onset of disease. One meta analysis and four observational studies examined the impact of genetic risk factors. Only specified mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were found to be linked to disease onset. One observational study evaluated a risk factor for the natural progression of disease. An extensive number of potential risk factors for the onset of spina bifida have been studied, though most lack sufficient evidence to confirm an association. Currently, strong evidence exists to suggest a causal association for maternal obesity prior to pregnancy, and paternal exposure to Agent Orange. PMID- 27000519 TI - Proceedings of the AST heart allocation meeting at the American Transplant Congress, Philadelphia, Pennsylvania, May 4, 2015. AB - Ensuring fair and equitable allocation of donor hearts in the US is the charge of the Organ Procurement and Transplantation Network (OPTN). However, the recent increase of candidates waiting without a corresponding increase in available donors, higher waitlist mortality rates in higher status patients, the presence of disadvantaged subgroups, and the changing management of heart failure patients with increased VAD usage, has necessitated review of allocation policy. Therefore, the Heart Subcommittee of the OPTN/UNOS Thoracic Committee is exploring a further-tiered allocation system, devising a "straw man" model as a starting point for modeling analyses and public discussion. On May 4, 2015, an American Society of Transplantation (AST)-endorsed forum to discuss these potential proposed changes took place. Attendees included 41 people, mostly highly experienced transplant cardiologists and cardiothoracic surgeons, representing 19 heart transplant centers across the US, UNOS, and the Scientific Registry of Transplant Recipients (SRTR). There was unanimous agreement that the potential proposed policy will require careful wording to avoid ambiguity and "gaming" of the system, and strong support for abolishment of local organ sharing in favor of geographic sharing. However, contention existed concerning the appropriate prioritization levels of ECMO, temporary VAD/TAH patients as well as the 30-day LVAD listing. PMID- 27000520 TI - At the Nexus of Food Security and Safety: Opportunities for Nanoscience and Nanotechnology. PMID- 27000522 TI - Phenotype-driven molecular autopsy for sudden cardiac death. AB - A phenotype-driven approach to molecular autopsy based in a multidisciplinary team comprising clinical and laboratory genetics, forensic medicine and cardiology is described. Over a 13 year period, molecular autopsy was undertaken in 96 sudden cardiac death cases. A total of 46 cases aged 1-40 years had normal hearts and suspected arrhythmic death. Seven (15%) had likely pathogenic variants in ion channelopathy genes [KCNQ1 (1), KCNH2 (4), SCN5A (1), RyR2(1)]. Fifty cases aged between 2 and 67 had a cardiomyopathy. Twenty-five had arrhythmogenic right ventricular cardiomyopathy (ARVC), 10 dilated cardiomyopathy (DCM) and 15 hypertrophic cardiomyopathy (HCM). Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1). Uptake of cascade screening in relatives was higher when a molecular diagnosis was made at autopsy. In three families, variants previously published as pathogenic were detected, but clinical investigation revealed no abnormalities in carrier relatives. With a conservative approach to defining pathogenicity of sequence variants incorporating family phenotype information and population genomic data, a molecular diagnosis was made in 15% of sudden arrhythmic deaths and 18% of cardiomyopathy deaths. PMID- 27000523 TI - Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain. AB - Transcranical direct current stimulation (tDCS) is a treatment known to ameliorate various neurological conditions and enhance memory and cognition in humans. tDCS has gained traction for its potential therapeutic value; however, little is known about its mechanism of action. Using a transgenic mouse expressing G-CaMP7 in astrocytes and a subpopulation of excitatory neurons, we find that tDCS induces large-amplitude astrocytic Ca(2+) surges across the entire cortex with no obvious changes in the local field potential. Moreover, sensory evoked cortical responses are enhanced after tDCS. These enhancements are dependent on the alpha-1 adrenergic receptor and are not observed in IP3R2 (inositol trisphosphate receptor type 2) knockout mice, in which astrocytic Ca(2+) surges are absent. Together, we propose that tDCS changes the metaplasticity of the cortex through astrocytic Ca(2+)/IP3 signalling. PMID- 27000524 TI - The plasma miR-125a, miR-361 and miR-133a are promising novel biomarkers for Late Onset Hypogonadism. AB - Circulating miRNAs have been shown to serve as diagnostic/prognostic biomarkers in cancers and other diseases. However, the role of plasma miRNAs in Late-onset hypogonadism (LOH) diagnosis is still unknown. Using Illumina HiSeq2000 sequencing at discovery phase, and then two-step validated by reverse transcriptase polymerase chain reaction (RT-PCR) assays in verification phases. We verified that the expression levels of miR-125a-5p, miR-361-5p and miR-133a-3p were significantly altered in LOH group compared to the control group. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.682, 0.698 and 0.765, respectively. The combination of three miRNAs showed a larger AUC (0.835) that was more efficient for the diagnosis of LOH. Among three miRNAs, miR-133a-3p had the best diagnostic value for LOH with 68.2% sensitivity and 77.3% specificity. Regression analyses show that miR-133a-3p level was negatively associated with the ageing males' symptoms (AMS) scale. However, miR-361-5p level was positively associated with serum testosterone concentrations. In summary, plasma miRNAs are differentially expressed between LOH and healthy controls. We validated three miRNAs that could act as novel biomarkers for diagnosis of LOH. These miRNAs may be involved in the development of LOH. However, further large and functional studies are warranted to confirm our findings. PMID- 27000525 TI - Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin. AB - Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 MUg/ml. It's antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 MUg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis. PMID- 27000526 TI - Putting scales into evolutionary time: the divergence of major scale insect lineages (Hemiptera) predates the radiation of modern angiosperm hosts. AB - The radiation of flowering plants in the mid-Cretaceous transformed landscapes and is widely believed to have fuelled the radiations of major groups of phytophagous insects. An excellent group to test this assertion is the scale insects (Coccomorpha: Hemiptera), with some 8,000 described Recent species and probably the most diverse fossil record of any phytophagous insect group preserved in amber. We used here a total-evidence approach (by tip-dating) employing 174 morphological characters of 73 Recent and 43 fossil taxa (48 families) and DNA sequences of three gene regions, to obtain divergence time estimates and compare the chronology of the most diverse lineage of scale insects, the neococcoid families, with the timing of the main angiosperm radiation. An estimated origin of the Coccomorpha occurred at the beginning of the Triassic, about 245 Ma [228-273], and of the neococcoids 60 million years later [210-165 Ma]. A total-evidence approach allows the integration of extinct scale insects into a phylogenetic framework, resulting in slightly younger median estimates than analyses using Recent taxa, calibrated with fossil ages only. From these estimates, we hypothesise that most major lineages of coccoids shifted from gymnosperms onto angiosperms when the latter became diverse and abundant in the mid- to Late Cretaceous. PMID- 27000527 TI - In Vitro Assessment Reveals Parameters-Dependent Modulation on Excitability and Functional Connectivity of Cerebellar Slice by Repetitive Transcranial Magnetic Stimulation. AB - Repetitive transcranial magnetic stimulation (rTMS) is an increasingly common technique used to selectively modify neural excitability and plasticity. There is still controversy concerning the cortical response to rTMS of different frequencies. In this study, a novel in vitro paradigm utilizing the Multi Electrodes Array (MEA) system and acute cerebellar slicing is described. In a controllable environment that comprises perfusion, incubation, recording and stimulation modules, the spontaneous single-unit spiking activity in response to rTMS of different frequencies and powers was directly measured and analyzed. Investigation using this in vitro paradigm revealed frequency-dependent modulation upon the excitability and functional connectivity of cerebellar slices. The 1-Hz rTMS sessions induced short-term inhibition or lagged inhibition, whereas 20-Hz sessions induced excitation. The level of modulation is influenced by the value of power. However the long-term response fluctuated without persistent direction. The choice of evaluation method may also interfere with the interpretation of modulation direction. Furthermore, both short-term and long-term functional connectivity was strengthened by 1-Hz rTMS and weakened by 20-Hz rTMS. PMID- 27000528 TI - The effects of long-term stress on neural dynamics of working memory processing: An investigation using ERP. AB - This study examined the neural dynamics of working memory (WM) processing under long-term stress. Forty participants who had been exposed to a long period of major exam preparation (six months) and twenty-one control participants performed a numerical n-back task (n = 1, 2) while electroencephalograms were recorded. Psychological and endocrinal measurements confirmed significantly higher levels of long-term stress for participants in the exam group. The exam group showed significantly increased P2 amplitude in the frontal-central sites in the 1-back and 2-back conditions, whereas other ERP components, including the P1, N1 and P3 and behavioral performance, were unchanged. Notably, the P2 effect was most pronounced in participants in the exam group who reported perceiving high levels of stress. The perceived stress scores positively correlated with the P2 amplitude in the 1-back and 2-back conditions. These results suggest that long term stress has an impact on attention and the initiation of the updating process in WM. PMID- 27000529 TI - Sakuranetin Induces Melanogenesis in B16BL6 Melanoma Cells through Inhibition of ERK and PI3K/AKT Signaling Pathways. AB - Sakuranetin (Sak) is considered one of the most important flavanone phytoalexins in regard to antimicrobial activity, and accumulation, in the rice plant. The current study determined that Sak strongly stimulates melanogenesis in B16BL6 melanoma cells in a dose-dependent manner. This flavonoid upregulates the expression of microphthalmia transcription factor (MITF) and reaches its maximum after 24 h. In addition, Sak was found to increase in vitro tyrosinase (Tyr) activity, along with time-dependent upregulation of Tyr, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2). Sakuranetin also decreased the proliferation rate in these cells without directly affecting their viability, as revealed by MTT and trypan blue assays. Further, Sak was shown to inhibit phosphorylation and activation of ERK1/2 from 12 h, without significantly affecting p38 and JNK phosphorylation. Sakuranetin was also found to inhibit the phosphorylation of AKT at threonine 308 and serine 473 and leads to activation of GSK3beta via decreased phosphorylation at serine 9. Taken together, these results demonstrate that Sak stimulates melanogenesis in B16 melanoma cells via inhibition of ERK1/2 and PI3K/AKT signaling pathways, which lead to upregulation of Tyr, TRP1, and TRP2. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27000530 TI - Liquid liothyronine to obtain target TSH in differentiated thyroid cancer patients. AB - In the last ten years a liquid formulation of liothyronine (L-T3) became available. To date, no studies on its systematic use have been reported. This study is aimed at assessing the reliability of liquid L-T3 in achieving target TSH in patients with differentiated thyroid cancers (DTC). Twenty-one high risk DTC patients in whom levothyroxine treatment up to 2.0 MUg/kg/day did not suppress TSH levels (i.e. >0.1 mIU/L) were selected. Maintaining the same L-T4 dose, they started to assume liquid L-T3 at an initial fixed dose of 3.55 MUg (5 drops). Further adjustments of L-T3 dose were tailored according to individual assessment. Initial serum TSH ranged from 0.8 to 12.0 mIU/L, when patients assumed high dose of L-T4 alone. Following the addition of a daily single dose of 3.55 MUg L-T3, the target TSH was attained in five patients (23.8%). After increasing L-T3 dose up to a mean of 7.3+/-3.4 MUg/day all patients reached target serum TSH (<0.1 mIU/L). The mean individual L-T3 dose was significantly correlated with the body weight and was 0.11+/-0.04 MUg/kg/day (p=0.013). Mean L T4:L-T3 ratio was 21:1. No patients showed skewed free-T3 or free-T4 values, neither experienced discomfort nor reported adverse events. Liquid L-T3 can be useful to achieve optimal TSH suppression in high risk DTC with not suppressed TSH on L-T4 alone. This formulation allows an individual tailoring of L-T3, minimizing risks of side effects as well as of overtreatment in these clinical conditions. PMID- 27000531 TI - Independent risk factors of 30-day outcomes in 1264 patients with peptic ulcer bleeding in the USA: large ulcers do worse. AB - BACKGROUND: Predictors of worse outcomes (rebleeding, surgery and death) of peptic ulcer bleeds (PUBs) are essential indicators because of significant morbidity and mortality rates of PUBs. However those have been infrequently reported since changes in medical therapy (PPI, proton pump inhibitors) and application of newer endoscopic haemostatic technique. AIMS: To determine: (i) independent risk factors for 30-day rebleeding, surgery, and death and (ii) whether ulcer size is an independent predictor of major outcomes in patients with severe PUB after successful endoscopic haemostasis and treatment with optimal medical (high dose IV PPI) vs. prior treatment (high dose IV histamine 2 antagonists - H2RAs). METHODS: A large prospectively followed population of patients hospitalised with severe PUBs between 1993 and 2011 at two US tertiary care academic medical centres, stratified by stigmata of recent haemorrhage (SRH) was studied. Using multivariable logistic regression analyses, independent risk factors for each outcome (rebleeding, surgery and death) up to 30 days were analysed. Effects for medical treatment (H2RA patients 1993-2005 vs. PPIs 2006 2011) were also analysed. RESULTS: A total of 1264 patients were included. For ulcers >=10 mm, the odds of 30-day rebleeding increased 6% per each 10% increase in ulcer size (OR 1.06, 95% CI 1.02-1.10, P = 0.0053). Other risk factors for 30 day rebleeding were major SRH, in-patient start of bleeding, and prior GI bleeding. Major SRH and ulcer size>=10 mm were predictors of 30-day surgery. Risk factors for 30-day death were major SRH, in-patient bleeding, and any initial platelet transfusion or fresh frozen plasma transfusion >=2 units. Among patients with major SRH and out-patient start of bleeding, larger ulcer size was also a risk factor for death (OR 1.08 per 10% increase in ulcer size, 95% CI 1.02-1.14, P = 0.0095). Ulcer size was a significant independent variable for both time periods. CONCLUSIONS: Ulcer size is a risk factor for worse outcomes after PUB and should be carefully recorded at initial endoscopy to improve patient triage and management. PMID- 27000532 TI - Influence of prior hyperventilation duration on respiratory chemosensitivity and cerebrovascular reactivity during modified hyperoxic rebreathing. AB - NEW FINDINGS: What is the central question of this study? We characterized and compared the cardiorespiratory and cerebrovascular responses to the 'Duffin' modified hyperoxic CO2 rebreathing test by randomly altering the prior hyperventilation duration. What is the main finding and its importance? Our main finding was that prior hyperventilation duration (1, 3 or 5 min) had no effect on cardiorespiratory and cerebrovascular responses to the hyperoxic rebreathing test, within individuals. These findings suggest that the standard 5 min prior hyperventilation duration used to clear body CO2 stores is unnecessary and can reasonably be shortened to 1 min, reducing protocol times and improving participant comfort. The 'Duffin' modified hyperoxic rebreathing test allows investigators to characterize and quantify the ventilatory and cerebrovascular responses to CO2 across a large physiological range, allowing quantification of basal ventilation and the ventilatory recruitment threshold (VRT). Although the standard protocol includes 5 min of prior hyperventilation to clear body CO2 stores, there is no experimental evidence that a full 5 min is required. We hypothesized that there would be no within-individual differences in the cardiorespiratory or cerebrovascular responses to rebreathing with shortened hyperventilation duration prior to hyperoxic rebreathing. Using a rebreathing apparatus, transcranial Doppler ultrasound and beat-to-beat blood pressure monitoring, we tested 19 participants in the supine position using three randomly assigned hyperoxic rebreathing tests with 1, 3 or 5 min of prior hyperventilation. We measured VRT (in Torr CO2 ), time to VRT (in seconds), central respiratory chemoreflex (breathing frequency, tidal volume and minute ventilation), cerebrovascular (middle and posterior cerebral artery velocity) and cardiovascular (heart rate and mean arterial pressure) responses to CO2 during hyperoxic rebreathing. Using linear regression and repeated-measures ANOVAs, we found no differences in any of the cardiorespiratory or cerebrovascular response magnitudes between trials (P > 0.05). The only difference observed was in the time to VRT (in seconds), whereby 1 min prior hyperventilation duration was shorter (135.4 +/- 19.7 s) than with 3 or 5 min prior hyperventilation (176.3 +/- 15.1 and 187.2 +/- 11.6 s, respectively; P < 0.001). Our findings indicate that 5 min of prior hyperventilation is unnecessary during modified rebreathing when using it to quantify respiratory or cerebrovascular responses and can be reasonably shortened to 1 min, reducing protocol times and improving participant comfort. PMID- 27000533 TI - Phylodynamics of avian influenza clade 2.2.1 H5N1 viruses in Egypt. AB - BACKGROUND: Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are widely distributed within poultry populations in Egypt and have caused multiple human infections. Linking the epidemiological and sequence data is important to understand the transmission, persistence and evolution of the virus. This work describes the phylogenetic dynamics of H5N1 based on molecular characterization of the hemagglutinin (HA) gene of isolates collected from February 2006 to May 2014. METHODS: Full-length HA sequences of 368 H5N1 viruses were generated and were genetically analysed to study their genetic evolution. They were collected from different poultry species, production sectors, and geographic locations in Egypt. The Bayesian Markov Chain Monte Carlo (BMCMC) method was applied to estimate the evolutionary rates among different virus clusters; additionally, an analysis of selection pressures in the HA gene was performed using the Single Likelihood Ancestor Counting (SLAC) method. RESULTS: The phylogenetic analysis of the H5 gene from 2006-14 indicated the presence of one virus introduction of the classic clade (2.2.1) from which two main subgroups were originated, the variant subgroup which was further subdivided into 2 sub divisions (2.2.1.1 and 2.2.1.1a) and the endemic subgroup (2.2.1.2). The clade 2.2.1.2 showed a high evolution rate over a period of 6 years (6.9 * 10(-3) sub/site/year) in comparison to the 2.2.1.1a variant cluster (7.2 * 10(-3) over a period of 4 years). Those two clusters are under positive selection as they possess 5 distinct positively selected sites in the HA gene. The mutations at 120, 154, and 162 HA antigenic sites and the other two mutations (129?, I151T) that occurred from 2009-14 were found to be stable in the 2.2.1.2 clade. Additionally, 13 groups of H5N1 HPAI viruses were identified based on their amino acid sequences at the cleavage site and "EKRRKKR" became the dominant pattern beginning in 2013. CONCLUSIONS: Continuous evolution of H5N1 HPAI viruses in Egypt has been observed in all poultry farming and production systems in almost all regions of the country. The wide circulation of the 2.2.1.2 clade carrying triple mutations (120, 129?, I151T) associated with increased binding affinity to human receptors is an alarming finding of public health importance. PMID- 27000534 TI - Infections complicating severe alcoholic hepatitis: Enterococcus species represent the most frequently identified pathogen. AB - BACKGROUND: Patients with acute alcoholic steatohepatitis are at a high risk for infections. To date, neither disease-specific pathogen patterns, nor typical sites of infection, nor antibiotic treatment strategies have been established for AH. AIMS: To characterize incidence of infections, pathogen spectrum, sites of infection, and related mortality of patients with AH under steroid therapy. METHODS: We retrospectively analyzed clinical data of 73 patients with severe alcoholic hepatitis (MELD >= 20). RESULTS: Infections were detected in 45 patients (73%). Patients who developed an infection after initiation of corticosteroid therapy had a higher 6-month mortality than patients without onset of infection after initiation of corticosteroid treatment (44% versus 24%, p = 0.116). The pathogen identified most frequently was Enterococcus species. DISCUSSION: Infections frequently complicate severe alcoholic hepatitis and affect survival. The high rate of Enterococcus infections suggests that commonly used antibiotics, such as cephalosporins and quinolones, may represent an ineffective choice of empiric antibiotic treatment for complicated AH. PMID- 27000535 TI - Personality and gender differences in global perspective. AB - Men's and women's personalities appear to differ in several respects. Social role theories of development assume gender differences result primarily from perceived gender roles, gender socialization and sociostructural power differentials. As a consequence, social role theorists expect gender differences in personality to be smaller in cultures with more gender egalitarianism. Several large cross-cultural studies have generated sufficient data for evaluating these global personality predictions. Empirically, evidence suggests gender differences in most aspects of personality-Big Five traits, Dark Triad traits, self-esteem, subjective well being, depression and values-are conspicuously larger in cultures with more egalitarian gender roles, gender socialization and sociopolitical gender equity. Similar patterns are evident when examining objectively measured attributes such as tested cognitive abilities and physical traits such as height and blood pressure. Social role theory appears inadequate for explaining some of the observed cultural variations in men's and women's personalities. Evolutionary theories regarding ecologically-evoked gender differences are described that may prove more useful in explaining global variation in human personality. PMID- 27000536 TI - Ex vivo optical frequency domain imaging and histopathology of malapposed drug eluting stent in coronary artery. PMID- 27000537 TI - Engaging high and low burden countries in the "TB end game". PMID- 27000538 TI - Bartonella henselae infection presenting with a picture of adult-onset Still's disease. AB - We report a patient with a clinical picture of suggestive for adult-onset Still's Disease (ASOD) due to Bartonella infection. A 42-year-old immunocompetent man was admitted with fever, rash, arthralgia and sore throat. As his clinical picture suggested ASOD except unusual skin manifestation, we treated him on steroid and ibuprofen. His fever and constitutional symptoms responded immediately within 24hrs of commencing therapy, yet rash and leukocytosis remained. Meanwhile, Bartonella infection was proved by culture of bone marrow. Minocyclin treatment started combined with hydroxychloroquine sulfate and the patient discharged with overall improvement. PMID- 27000539 TI - Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse. AB - Interference of bile salt transport is one of the underlying mechanisms for drug induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time- and bile-acid-concentration dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 MUM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. PMID- 27000540 TI - Use of V agents and V-analogue compounds to probe the active site of atypical butyrylcholinesterase from Oryzias latipes. AB - The atypical butyrylcholinesterase (aBuChE) from Oryzias latipes shares approximately 65% sequence similarity to both acetylcholinesterase and butyrylcholinesterase and was studied for its capacity to spontaneously reactivate following inhibition by organophosphorus nerve agents. Like other cholinesterases, aBuChE was inhibited by all G- and V-type nerve agents. Interestingly, aBuChE was able to undergo spontaneous reactivation after inhibition with VR (t1/2 = 5.5 +/- 0.2 h). Mass spectrometry of aBuChE after VR inhibition confirmed the presence of a covalently bound adduct of the size expected for non-aged VR on the peptide containing the active site serine. To understand the effect of substrate volume on rates of reactivation, the capacity of aBuChE to bind and spontaneously reactivate after inhibition with five V-agent analogues was examined. No appreciable reactivation was detected for enzyme inhibited by V2 (VX with O-isopropyl on retained group), V4 (VX with N-diethyl leaving group termination), or V5 (VX with N-dimethyl leaving group termination). Minimal reactivation was detected with V1 (VX with O-propyl on retained group). Conversely, spontaneous reactivation was observed when aBuChE was inhibited by V3 (VX with O-isobutyl on retained group; t1/2 = 6.3 +/- 0.4 h). The data suggest that the ability of aBuChE to spontaneously reactivate after inhibition by V agent analogues is related to the structure of the retained group. These results provide structural information that may shed light on the design of improved small molecule reactivators of nerve agent-inhibited acetylcholinesterase or butyrylcholinesterase, and further suggest that re-engineering the active site of a cholinesterase could result in enzymes with clinically relevant rates of nerve agent hydrolysis. PMID- 27000541 TI - The role of research in the prevention of mental disorders. PMID- 27000542 TI - Therapeutic relationship on the web: to face or not to face? AB - In this age of unprecedented expansion of media and information dissemination and sharing, the use of electronic means should be reconsidered. The use of new technologies should be studied to understand how it may affect the relationship between patient and therapist during psychotherapy or psychoanalytic treatments. This study offers a critical discussion of the effect of technologies on clinical practice, and vignettes are used to describe their impact on frame, anonymity, abstinence and therapeutic neutrality. Transfer and countertransference issues resulting from these changes are also discussed. The potential benefits of new technologies in psychotherapy are appreciated, but the authors draw attention to the need to reflect about the presence of the therapist in those technologies and the preservation of the therapeutic setting, so that a satisfactory progression of the work of the dyad is ensured. This study also discusses the use of technologies in the expansion of learning and application of the therapeutic technique to overcome geographic and time barriers, among others. PMID- 27000543 TI - Temporomandibular disorders and eating disorders: a literature review. AB - INTRODUCTION: Temporomandibular disorders (TMD) and eating disorders (ED) affect function and parafunction of the oral cavity and have high rates of medical and psychological comorbidity. However, little is known about the possible associations between them, and few studies have investigated the existence of such associations. METHODS: A search was conducted on the SciELO, LILACS, and PubMed/MEDLINE databases to find relevant articles written in English and Portuguese. Only studies involving human beings were included, and there was no limit for year of publication. RESULTS AND CONCLUSIONS: There is evidence of the correlation between TMD and ED, but their comorbidity must be better understood. The presence of depressive symptoms is an aggravating factor that must also be taken into account during the diagnosis and treatment of those patients. PMID- 27000544 TI - The progression of 102 Brazilian patients with bipolar disorder: outcome of first 12 months of prospective follow-up. AB - INTRODUCTION: Prospective studies have shown that the course of bipolar disorder (BD) is characterized by the persistence of symptoms, predominantly depression, along most of the time. However, to our knowledge, no studies in Latin America have investigated it. OBJECTIVES: To replicate international studies using a Brazilian sample to prospectively analyze treatment outcomes in the first year and to determine potential chronicity factors. METHODS: We followed up 102 patients with BD for 12 months and evaluated the number of months with affective episodes and the intensity of manic and depressive symptoms using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Scale (HAM-D17). Sociodemographic and retrospective clinical data were examined to determine possible predictors of outcome. RESULTS: Almost 50% of the patients had symptoms about half of the time, and there was a predominance of depressive episodes. Disease duration and number of depressive episodes were predictors of chronicity. Depressive polarity of the first episode and a higher number of depressive episodes predicted the occurrence of new depressive episodes. CONCLUSION: In general, BD outcome seems to be poor in the first year of monitoring, despite adequate treatment. There is a predominance of depressive symptoms, and previous depressive episodes are a predictor of new depressive episodes and worse outcome. PMID- 27000545 TI - Psychometric properties of the revised conscientiousness dimension of Inventario Dimensional Clinico da Personalidade (IDCP). AB - This study investigated the psychometric properties of the revised scale of conscientiousness of a clinical personality inventory (Inventario Dimensional Clinico da Personalidade, IDCP). One hundred and twenty participants (68 women; 56.7%) aged 18 to 53 years (mean = 22.58, standard deviation = 6.19) were recruited by convenience and answered the IDCP and the NEO Personality Inventory Revised. The analysis of internal structure, association with external variables and reliability of the dimension under review confirmed its validity. The psychometric characteristics of the revised dimension seem to be more adequate than those of the original version and more focused on pathological functioning, which was expected and desirable. PMID- 27000546 TI - Influence of body posture on the association between postpartum depression and pain. AB - OBJECTIVE: To determine the association between postpartum depression (PPD), intensification of back pain and exacerbation of changes in postural alignment intrinsic to puerperium. METHODS: Eighty women at 2 to 30 weeks postpartum were included in the study according to the following criteria: literate mothers, gestation of 34 to 42 weeks, and healthy live-born infants. All mothers agreed to participate in the study. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS). Pain was assessed using a visual analogue scale (VAS) and the Nordic Musculoskeletal Questionnaire (NMQ), and posture, using real time naturalistic observation. RESULTS: There was a statistically significant association between PPD and pain intensity (p = 0.002). The upper back was the most frequent pain site among depressed women, both before (p = 0.04) and after delivery (p = 0.01). There were no associations between PPD and type of posture (p = 0.328). However, pain intensity was greater among depressed women in the swayback group (p < 0.001). CONCLUSION: The intensification of puerperal pain is closely associated with PPD. Our results suggest that back pain may be both a risk factor and a comorbidity of PPD among puerperal women and that pain and type of posture are interdependent. PMID- 27000547 TI - Brazilian Portuguese version of the Patient Competency Rating Scale (PCRS-R-BR): semantic adaptation and validity. AB - This study describes the adaptation of a revised Brazilian version of the Patient Competency Rating Scale (PCRS-R-BR), which focuses on executive, mnemonic, and attention functions. Evidence of content-based and external validity is also reported. The cross-cultural adaptation was conducted in five phases: 1) translations and back translations; 2) item analysis by authors; 3) classification by experts; 4) revisions and reformulations by authors; 5) pilot study with a sample of patients with mild and moderate/severe traumatic brain injury (TBI). Data were analyzed descriptively, and the PCRS-R-BR scores of groups with mild vs. moderate/severe TBI were compared using the Mann-Whitney test. Patients and their relatives were divided into groups and compared using repeated-measures analysis. The results of the PCRS-R-BR questionnaire for relatives and discrepancy scores of patients with moderate/severe TBI revealed significantly more impairment than that found in the group of patients with mild TBI. There were significant differences between item and total scores of both groups of patients and relatives. Results indicated a high level of item content agreement between experts. This study found initial evidence of PCRS-R-BR content based and external validity when the questionnaire was applied to patients with mild and moderate/severe TBI and their relatives. PMID- 27000548 TI - Forty years of a psychiatric day hospital. AB - INTRODUCTION: Day hospitals in psychiatry are a major alternative to inpatient care today, acting as key components of community and social psychiatry. OBJECTIVE: To study trends in the use of psychiatric day hospitals over the last decades of the 20th century and the first decade of the 21st century, focusing on patient age, sex, and diagnostic group, using data from Centro Hospitalar Sao Joao, Porto, Portugal. METHODS: Data corresponding to years 1970 to 2009 were collected from patient files. Patients were classified into seven diagnostic groups considering their primary diagnoses only. RESULTS: Mean age upon admission rose from 32.7+/-12.1 years in the second half of the 1970s to 43.5+/-12.2 years in 2005-2009 (p for trend < 0.001). Most patients were female (63.2%), however their proportion decreased from nearly 70% in the 1970s to 60% in the first decade of the 21st century. In males, until the late 1980s, neurotic disorders (E) were the most common diagnosis, accounting for more than one third of admissions. In the subsequent years, this proportion decreased, and the number of admissions for schizophrenia (C) exceeded 50% in 2004- 2009. In females, until the late 1980s, affective disorders (D) and neurotic disorders (E), similarly distributed, accounted for most admissions. From the 1990s on, the proportion of neurotic disorders (E) substantially decreased, and affective disorders (D) came to represent more than 50% of all admissions. CONCLUSIONS: Mean age upon admission rose with time, as did the percentage of female admissions, even though the latter tendency weakened in the last 10 years assessed. There was also an increase in the proportion of patients with schizophrenia. PMID- 27000549 TI - Dual light chain extramedullary myeloma presenting with mediastinal lymphadenopathy and lytic bone lesions. PMID- 27000550 TI - Stimulatory effect of cobalt ions incorporated into calcium phosphate coatings on neovascularization in an in vivo intramuscular model in goats. AB - Rapid vascularization of bone graft substitutes upon implantation is one of the most important challenges to overcome in order to achieve successful regeneration of large, critical-size bone defects. One strategy for stimulating vascularization during the regeneration process is to create a hypoxic microenvironment by either directly lowering the local oxygen tension, or by applying hypoxia-mimicking factors. Cells compensate for the hypoxic condition by releasing angiogenic factors leading to new blood vessel formation. In the present study, we explored the potential of cobalt ions (Co(2+)), known chemical mimickers of hypoxia, to stimulate vascularization within a bone graft substitute in vivo. To this end, Co(2+) ions were incorporated into calcium phosphate (CaPs) coatings deposited on poly(lactic acid) (PLA) particles with their effect on the formation of new blood vessels studied upon intramuscular implantation in goats. PLA particles and CaP-coated particles without Co(2+) ions served as controls. Pathological scoring of the inflammatory response following a 12-week implantation period showed no significant differences between the four types of materials. Based on histological and immunohistochemical analyses, both blood vessel area and number of blood vessels in CaP-coated PLA particles containing Co(2+) were higher than in the uncoated PLA particles and CaP-coated PLA particles without Co(2+). Analysis of blood vessel size distribution indicated abundant formation of small blood vessels in all the samples, while large blood vessels were predominantly found in PLA particles coated with CaP containing Co(2+) ions. The results of this study support the use of CaPs containing Co(2+) ions to enhance vascularization in vivo. STATEMENT OF SIGNIFICANCE: In this work, we have investigated the potential of cobalt ions, incorporated into thin calcium phosphate (CaP) coatings that were deposited on particles of poly(lactic acid) (PLA), to induce neovascularization in vivo. Qualitative and quantitative histological and immunohistochemical analyses showed that both the number of blood vessels and the total blood vessel area were higher in CaP-coated PLA particles containing cobalt ions as compared to the uncoated PLA particles and CaP-coated PLA particles without the metallic additive. Furthermore, a wider distribution of blood vessel sizes, varying from very small to large vessels was specifically observed in samples containing cobalt ions. This in vivo study will significantly contribute to the existing knowledge on the use of bioinorganics, which are simple and inexpensive inorganic factors that can be used to control relevant biological process during tissue regeneration, such as vascularization. As such, we are convinced that this manuscript will be of interest to the readers of Acta Biomaterialia. PMID- 27000551 TI - RGD and BMP-2 mimetic peptide crosstalk enhances osteogenic commitment of human bone marrow stem cells. AB - Human bone marrow mesenchymal stem cells (hBMSCs) commitment and differentiation are dictated by bioactive molecules sequestered within their Extra Cellular Matrix (ECM). One common approach to mimic the physiological environment is to functionalize biomaterial surfaces with ECM-derived peptides able to recruit stem cells and trigger their linage-specific differentiation. The objective of this work was to investigate the effect of RGD and BMP-2 ligands crosstalk and density on the extent of hBMSCs osteogenic commitment, without recourse to differentiation medium. RGD peptide promotes cell adhesion via cell transmembrane integrin receptors, while BMP-2 peptide, corresponding to residues 73-92 of Bone Morphogenetic Protein-2, was shown to induce hBMSCs osteoblast differentiation. The immobilization of peptides on aminated glass was ascertained by X-ray Photoelectron Spectroscopy (XPS), the density of grafted peptides was quantified by fluorescence microscopy and the surface roughness was evaluated using Atomic Force Microscopy (AFM). The osteogenic commitment of hBMSCs cultured on RGD and/or BMP-2 surfaces was characterized by immunohistochemistry using STRO-1 as specific stem cells marker and Runx-2 as an earlier osteogenic marker. Biological results showed that the osteogenic commitment of hBMSCs was enhanced on bifunctionalized surfaces as compared to surfaces containing BMP-2, while on RGD surfaces cells mainly preserved their stemness character. These results demonstrated that RGD and BMP-2 mimetic peptides act synergistically to enhance hBMSCs osteogenesis without supplementing the media with osteogenic factors. These findings contribute to the development of biomimetic materials, allowing a deeper understanding of signaling pathways that govern the transition of stem cells towards the osteoblastic lineage. STATEMENT OF SIGNIFICANCE: For a long time, scientists thought that the differentiation of Mesenchymal Stem Cells (MSCs) into bone cells was dictated by growth factors. This manuscript shed light on other ligands that play a crucial role in regulating MSCs fate. In concrete terms, it was demonstrated that the osteoinductive effect of BMP-2 peptide is 2 folds improved in the presence of adhesive RGD peptide. Compared to previous works highlighting this synergistic cooperation between RGD and BMP-2 peptides, the main strength of this work lies to the use of primitive human cells (hMSCs) and well-defined biomimetic material surfaces (controlled surface roughness and peptide densities). This work provides valuable insights to develop custom designed in vitro cell culture models, capable of targeting the desired cell response. PMID- 27000553 TI - Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting. AB - In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26week implantation in adult sheep femora. Despite higher total bone implant contact for Ti6Al4V (39+/-4%) than CoCr (27+/-4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications. STATEMENT OF SIGNIFICANCE: Although cobalt chromium (CoCr) based alloys are used extensively in orthopaedic surgery, stress shielding due to the high stiffness of CoCr is of concern. To reduce the stiffness mismatch between CoCr and bone, CoCr and Ti6Al4V implants having an interconnected open-pore architecture were prepared by electron beam melting (EBM). After six months of submerged healing in sheep, both alloys showed similar patterns of bone formation, with densification around the implant and gradual ingrowth into the porous network. The molecular and elemental composition of the interfacial tissue was similar for both alloys. Osteocytes made direct contact with both alloys, with similar overall osteocyte density and distribution. The work attests to the potential for achieving osseointegration of EBM manufactured porous CoCr implants. PMID- 27000552 TI - Fluorinated methacrylamide chitosan hydrogels enhance collagen synthesis in wound healing through increased oxygen availability. AB - In this study, methacrylamide chitosan modified with perfluorocarbon chains (MACF) is used as the base material to construct hydrogel dressings for treating dermal wounds. MACF hydrogels saturated with oxygen (+O2) are examined for their ability to deliver and sustain oxygen, degrade in a biological environment, and promote wound healing in an animal model. The emerging technique of metabolomics is used to understand how MACF+O2 hydrogel dressings improve wound healing. Results indicate that MACF treatment facilitates oxygen transport rate that is two orders of magnitude greater than base MAC hydrogels. MACF hydrogel dressings are next tested in an in vivo splinted rat excisional wound healing model. Histological analysis reveals that MACF+O2 dressings improve re-epithelialization (p<0.0001) and synthesis of collagen over controls (p<0.01). Analysis of endogenous metabolites in the wounds using global metabolomics demonstrates that MACF+O2 dressings promotes a regenerative metabolic process directed toward hydroxyproline and collagen synthesis, with confirmation of metabolite levels within this pathway. The results of this study confirm that increased oxygen delivery through the application of MACF+O2 hydrogels enhances wound healing and metabolomics analyses provides a powerful tool to assess wound healing physiology. STATEMENT OF SIGNIFICANCE: This work presents the first application of a novel class of oxygen delivering biomaterials (methacrylamide chitosan modified with perfluorocarbon chains (MACF)) as a hydrogel wound dressing. This manuscript also contains strong focus on the biochemical benefits of MACF dressings on underlying mechanisms vital to successful wound healing. In this vein, this manuscript presents the application of applied metabolomics (tandem mass spectroscopy) to uncover biomaterial interactions with wound healing mechanisms. We believe the approaches described in this manuscript will be of great interest to biomedical scientists and particularly to researchers studying wound healing, metabolomics, applied biomaterials and regenerative medicine. PMID- 27000554 TI - Structural analysis of the tongue and hyoid apparatus in a woodpecker. AB - Woodpeckers avoid brain injury while they peck at trees up to 20Hz with speeds up to 7m/s, undergoing decelerations up to 1200g. Along with the head, beak and neck, the hyoid apparatus (tongue bone and associated soft tissues) is subjected to these high impact forces. The shape of the hyoid apparatus is unusual in woodpeckers and its structure and mechanical properties have not been reported in detail. High-resolution X-ray micro-computed tomography and scanning electron microscopy with energy dispersive X-ray spectroscopy were performed and correlated with nanoindentation mapping. The hyoid apparatus has four distinct bone sections, with three joints between these sections. Nanoindentation results on cross-sectional regions of each bone reveal a previously unreported structure consisting of a stiff core and outer, more compliant shell with moduli of up to 27.4GPa and 8.5GPa, respectively. The bending resistance is low at the posterior section of the hyoid bones, indicating that this region has a high degree of flexibility to absorb impact. These new structural findings can be applied to further studies on the energy dissipation of the woodpecker during its drumming behavior, and may have implications for the design of engineered impact-absorbing structures. STATEMENT OF SIGNIFICANCE: Woodpeckers avoid brain injury while they peck at trees, which results in extreme impact conditions. One common adaptation in woodpeckers is the unusual shape of the elongated tongue, also called the hyoid apparatus. The relationship between the structure and mechanical properties of the bony part of the hyoid apparatus has not been previously reported. A three dimensional model of the bony tongue was developed, and the hardness and stiffness were evaluated. A new type of bone structure, which is opposite of typical skeletal bone structure was found. The combined microstructural and mechanical property analysis indicate possible energy absorption routes for the hyoid apparatus and are applicable to the design of engineered structures. PMID- 27000555 TI - Non-genetic polymorphisms in rotifers: environmental and endogenous controls, development, and features for predictable or unpredictable environments. AB - Pronounced non-genetic polymorphisms, or polyphenisms, occur in some monogonont rotifers reproducing by diploid, female parthenogenesis. In many brachionids, there is great variation in spine length. In trimorphic species of Asplanchna, females can vary in size and shape, from a small saccate morph to giant cruciform and campanulate morphs. In species that also reproduce sexually, diploid eggs can develop into two types of females. Amictic females produce diploid eggs that develop parthenogenetically into females; mictic females produce haploid eggs that develop parthenogenetically into males or, if fertilized, into resting eggs. In a species of Synchaeta, amictic females produce diploid eggs that can be either thin-shelled and subitaneous or thicker-shelled and diapausing. In all cases, morph determination occurs during the oogenesis or embryological development of diploid eggs in the maternal body cavity. For the first time, these polymorphisms are reviewed together and compared regarding a number of features associated with transitions from default to induced morphs: (i) type of variation (morphological, physiological, or both; continuous or discrete); (ii) inducing signal (environmental, endogenous, or both); (iii) universality of response to that signal (all or only some individuals); (iv) fitness cost; (v) reversibility; and (vi) ecological significance. Most of the polymorphisms fall into two major categories regarding these features. Transitions suitable for predictable environments involve: universal responses to environmental signals; continuous morphological variation; low reproductive cost; rapid reversibility; and adaptations for defence, hydrodynamics or prey ingestion. Transitions suitable for unpredictable environments are bet-hedging strategies and usually involve: partial (stochastic) responses to environmental or endogenous signals; discontinuous physiological variation; initiation of diapause, and thus high reproductive cost and slow reversibility. Two cases of morphological variation also involve the simultaneous production of different morphs and likely are adaptations for an uncertain future: continuous spine-length variation due to maternal age in Brachionus calyciflorus, and production of discrete cruciform and campanulate females in Asplanchna spp. PMID- 27000556 TI - The role of astrocytes in the hypothalamic response and adaptation to metabolic signals. AB - The hypothalamus is crucial in the regulation of homeostatic functions in mammals, with the disruption of hypothalamic circuits contributing to chronic conditions such as obesity, diabetes mellitus, hypertension, and infertility. Metabolic signals and hormonal inputs drive functional and morphological changes in the hypothalamus in attempt to maintain metabolic homeostasis. However, the dramatic increase in the incidence of obesity and its secondary complications, such as type 2 diabetes, have evidenced the need to better understand how this system functions and how it can go awry. Growing evidence points to a critical role of astrocytes in orchestrating the hypothalamic response to metabolic cues by participating in processes of synaptic transmission, synaptic plasticity and nutrient sensing. These glial cells express receptors for important metabolic signals, such as the anorexigenic hormone leptin, and determine the type and quantity of nutrients reaching their neighboring neurons. Understanding the mechanisms by which astrocytes participate in hypothalamic adaptations to changes in dietary and metabolic signals is fundamental for understanding the neuroendocrine control of metabolism and key in the search for adequate treatments of metabolic diseases. PMID- 27000557 TI - Surgical removal and controlled trypsinization of the outer annulus fibrosus improves the bioactivity of the nucleus pulposus in a disc bioreactor culture. AB - BACKGROUND: The maintenance of nucleus pulposus (NP) viability in vitro is difficult. The annulus fibrosus (AF) pathway reflects one nutrient transport channel and may have an important effect on NP viability in disc organ cultures. The present study describes a feasible disc pre-treatment involving the AF and investigates its efficacy in improving NP bioactivity in an in vitro disc bioreactor culture. METHODS: Rabbit discs that were randomly assigned to the experimental group (EG) were pretreated via the surgical removal and controlled trypsinization of the outer AF. The discs in the control group (CG) did not receive any special treatment. All discs were organ-cultured in a self-developed bioreactor. Solute transport into the central NP was measured using a methylene blue solution. On days 7 and 14, histological properties, cell viability, cell membrane damage, gene expression and matrix composition within the NP in these two groups were compared with each other and with the corresponding parameters of fresh NP samples. Additionally, the structures of the outer AF and the cartilage endplate (CEP) following pre-treatment were also assessed. RESULTS: The outer AF in the EG became disorganized, but no specific changes occurred in the CEP or the inner AF following pre-treatment. The discs in the EG exhibited increased penetration of methylene blue into the central NP. On days 7 and 14, the NP bioactivity in the EG was improved compared with that of the CG in terms of cell viability, cell membrane damage, gene expression profile and matrix synthesis. Moreover, cell viability and matrix synthesis parameters in the EG were more similar to those of fresh samples than they were to the same parameters in the CG on day 14. CONCLUSIONS: Using this disc pre-treatment, i.e., the surgical removal and controlled trypsinization of the outer AF, NP bioactivity was better maintained for up to 14 days in an in vitro disc bioreactor culture. PMID- 27000558 TI - Signal processing in urodynamics: towards high definition urethral pressure profilometry. AB - BACKGROUND: Urethral pressure profilometry (UPP) is used in the diagnosis of stress urinary incontinence (SUI) which is a significant medical, social, and economic problem. Low spatial pressure resolution, common occurrence of artifacts, and uncertainties in data location limit the diagnostic value of UPP. To overcome these limitations, high definition urethral pressure profilometry (HD UPP) combining enhanced UPP hardware and signal processing algorithms has been developed. In this work, we present the different signal processing steps in HD UPP and show experimental results from female minipigs. METHODS: We use a special microtip catheter with high angular pressure resolution and an integrated inclination sensor. Signals from the catheter are filtered and time-correlated artifacts removed. A signal reconstruction algorithm processes pressure data into a detailed pressure image on the urethra's inside. Finally, the pressure distribution on the urethra's outside is calculated through deconvolution. A mathematical model of the urethra is contained in a point-spread-function (PSF) which is identified depending on geometric and material properties of the urethra. We additionally investigate the PSF's frequency response to determine the relevant frequency band for pressure information on the urinary sphincter. RESULTS: Experimental pressure data are spatially located and processed into high resolution pressure images. Artifacts are successfully removed from data without blurring other details. The pressure distribution on the urethra's outside is reconstructed and compared to the one on the inside. Finally, the pressure images are mapped onto the urethral geometry calculated from inclination and position data to provide an integrated image of pressure distribution, anatomical shape, and location. CONCLUSIONS: With its advanced sensing capabilities, the novel microtip catheter collects an unprecedented amount of urethral pressure data. Through sequential signal processing steps, physicians are provided with detailed information on the pressure distribution in and around the urethra. Therefore, HD UPP overcomes many current limitations of conventional UPP and offers the opportunity to evaluate urethral structures, especially the sphincter, in context of the correct anatomical location. This could enable the development of focal therapy approaches in the treatment of SUI. PMID- 27000560 TI - Clearance rates of residual stone fragments and dusts after endoscopic lithotripsy procedures using a holmium laser: 2-year follow-up results. AB - PURPOSE: To investigate the spontaneous clearance rates of remnant particles following miniaturized percutaneous nephrolithotomy (mini-PCNL) and retrograde intrarenal surgery (RIRS). METHODS: Among 624 patients who underwent mini-PCNL or RIRS at our institution from 2011 to 2015, we collected data of 247 patients with 2 years of follow-up. Of these, we included 148 patients with unilateral renal stones between 10 and 30 mm, as well as remnant particles after surgery. The size criteria of dusts and residual fragments (RFs) were, respectively, <1 and <3 mm. RESULTS: After excluding 22 patients, 126 patients (RFs = 21, dusts = 98, and both RFs and dusts = 7) were analyzed. Mean age was 56.5 (+/-14.4) years, and mean stone size was 19.5 (+/-12.5) mm. The mean follow-up period was 18.5 (+/- 12.9) months. In patients whose remnant particles were naturally eliminated following lithotripsy, the mean stone passage time was 9.0 (+/-9.3) months in the dusts and 13.9 (+/-11.1) months in the RFs groups (P = 0.135). Remnant particles disappeared in 42 out of 105 patients (40.0 %) in dusts and 7 out of 28 patients (25.0 %) in RFs groups (P = 0.187). The size of dusts and RFs increased, respectively, in 18.1 % (19/105) and 28.6 % (8/28) of patients with remnant particles during the follow-up period. CONCLUSIONS: The presence of dusts and RFs was poor prognostic factors in patients underwent renal stone surgery using a holmium laser. Complete residual stone removal by using a basket or dusts eradication by irrigation for an adequate time during surgery can be a good surgical strategy. PMID- 27000561 TI - Tumor diameter accurately predicts perioperative outcomes in T1 renal cancer treated with robot-assisted partial nephrectomy. AB - PURPOSE: To compare diameter as a continuous variable with categorical R.E.N.A.L. nephrometry score (RNS) in predicting surgical outcomes of robotic partial nephrectomy (RPN). METHODS: We retrospectively reviewed consecutive patients receiving RPN at our institution between July 2007 and June 2014 (n = 286). Three separate multivariate analyses were performed to assess the relationship between RNS components (R = radius, E = endophyticity, N = nearness to collecting system, L = location relative to polar lines), total RNS, and diameter as a continuous variable with operating time, warm ischemia time (WIT), and estimated blood loss (EBL). Each linear regression model's quality of fit to the data was assessed with coefficients of determination (R 2). RESULTS: Continuous tumor diameter and total RNS were each significantly correlated to operative time, EBL, and WIT (p < 0.001). Categorical R related to operative time (R = 2 vs. R = 1, p = 0.001; R = 3 vs. R = 1, p = 0.001) and WIT (R = 2 vs. R = 1, p = 0.003; R = 3 vs. R = 1, p = 0.016), but not to EBL. For each of these outcomes, diameter outperformed both R and total RNS, as assessed by R 2. Age, body mass index, Charlson Comorbidity Index, and anterior versus posterior location did not correlate with surgical outcomes. CONCLUSIONS: In this series of RPN from a high-volume center, surgical outcomes more closely related to tumor diameter than RNS. While RNS provides surgeons a standardized tool for preoperative planning of renal masses, tumor size may be employed as a more familiar measurement when counseling patients on potential outcomes. PMID- 27000562 TI - Determining the core, corona, and total size of CdSeS/ZnS quantum dots by SEC/QELS and TEM. AB - The size (hydrodynamic or Stokes radius, R H) of non-functionalized CdSeS/ZnS (core/shell) quantum dots (QDs) was characterized by size-exclusion chromatography with on-line quasi-elastic light scattering (SEC/QELS). Accurate determination of the size of QDs is important, because many of the optical properties of these materials are size dependent. A clear advantage of SEC/QELS over many batch techniques (e.g., QELS without separation) is the capability of the hyphenated technique to characterize the entire size range of a disperse sample, rather than merely providing a statistical average of the sizes present. Here, the SEC/QELS-determined R H values of CdSeS/ZnS QDs are compared to those determined by a traditional SEC experiment employing a calibration curve based on polystyrene standards, providing for the first reported study on SEC/QELS of non functionalized QDs while also demonstrating the shortcomings of the widely employed calibration curve approach. Furthermore, combining the R H of the QDs obtained by SEC/QELS with core size measurements derived from transmission electron microscopy allowed further calculation of the size of the QDs' coronas. The latter result was found to be in close agreement to the previously measured dimension of the main corona constituent, as well as with the calculated size of this constituent. PMID- 27000559 TI - Targeting Antibiotic Resistance. AB - Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human-pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last-resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled "Combat drug resistance: no action today means no cure tomorrow" triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens. PMID- 27000563 TI - Development of a quantitation method to assay both lyoniresinol enantiomers in wines, spirits, and oak wood by liquid chromatography-high resolution mass spectrometry. AB - Wine taste balance evolves during oak aging by the release of volatile and non volatile compounds from wood. Among them, an enantiomer of lyoniresinol, (+) lyoniresinol, has been shown to exhibit bitterness. To evaluate the impact of (+) lyoniresinol on wine taste, a two-step quantitation method was developed and validated. First, (+/-)-lyoniresinol was assayed in wines, spirits, and oak wood macerates by C-18 liquid chromatography-high resolution mass spectrometry (LC HRMS). Then, the lyoniresinol enantiomeric ratio was determined by chiral LC-HRMS in order to calculate the (+)-lyoniresinol content. In red and white wines, the average concentrations of (+)-lyoniresinol were 1.9 and 0.8 mg/L, respectively. The enantiomer proportions were not affected by bottle aging, and lyoniresinol appeared to remain stable over time. The sensory study of (+)-lyoniresinol established its perception threshold at 0.46 mg/L in wine. All the commercial wines quantitated were above this perception threshold, demonstrating its impact on wine taste by an increase in bitterness. In spirits, (+)-lyoniresinol ranged from 2.0 to 10.0 mg/L and was found to be released continuously during oak aging. Finally, neither botanical origin nor toasting was found to significantly affect the (+)-lyoniresinol content of oak wood. Graphical abstract From oak wood to wine: evaluation of the influence of (+)-lyoniresinol on the bitterness of wines and spirits. PMID- 27000564 TI - Determination of 2-alkylcyclobutanones by combining precolumn derivatization with 1-naphthalenyl hydrazine and ultra-performance liquid chromatography with fluorescence detection. AB - 2-Alkylcyclobutanones (2-ACBs) are uniquely formed when triglycerides-containing food products are exposed to ionizing radiation. Thus, 2-ACBs have been used as marker molecules to identify irradiated food. Most methods to determine 2-ACBs involve mass spectrometric detection after chromatographic separation. The spectrofluorometer is rarely used to determine 2-ACBs because these molecules do not fluoresce. In this study, we developed an ultra-performance liquid chromatography (UPLC) method to determine 2-ACBs. 2-ACBs were converted into fluorophores after reacting with 1-naphthalenyl hydrazine to facilitate their sensitive and selective detection using a fluorescence detector (FLD). Analysis of 2-ACBs using our developed UPLC-FLD method allows sensitive determination of 2 ACBs at a detection limit of 2 ng 2-ACBs per g of fat (30 pg/injection), which is significantly lower than that of existing analytical methods. After validation for trueness and precision, the method was applied to gamma-irradiated chicken samples to determine their 2-ACB content. Comparative studies employing liquid chromatography-tandem mass spectrometric method revealed no systematic difference between the two methods, thereby demonstrating that the proposed UPLC-FLD method can be suitably used to determine 2-ACBs in irradiated foodstuffs. Graphical Abstract Determination of radiation-induced food-borne 2-dodecylcyclobutanone and 2-tetradecylcyclobutanone by combining 1-naphthalenyl hydrazine derivatization and ultra-performance liquid chromatography with fluorescence detection. PMID- 27000565 TI - Common molecular mechanism of the hepatic lesion and the cardiac parasympathetic regulation in chronic hepatitis C infection: a critical role for the muscarinic receptor type 3. AB - BACKGROUND: The pathophysiological overlapping between Sjorgen's Syndrome (SS) and HCV, presence of anti- muscarinic receptor type 3 (M3R) antibodies in SS, the role that M3R plays in the regulation of the heart rate, has led to the assumption that cardiovagal dysfunction in HCV patients is caused by anti-M3R antibodies elicited by HCV proteins or by their direct interaction with M3R. RESULTS: To identify HCV protein which possibly is crossreactive with M3R or which binds to this receptor, we performed the Informational Spectrum Method (ISM) analysis of the HCV proteome. This analysis revealed that NS5A protein represents the most probable interactor of M3R or that this viral protein could elicit antibodies which modulate function of this receptor. Further detailed structure/function analysis of NS5A and M3R performed by the ISM method extended with other Digital Signal processing (DSP) approaches revealed domains of these proteins which participate in their crossreactivity or in their direct interaction, representing promising diagnostic and therapeutic targets. CONCLUSIONS: Application of the ISM with other compatible bioinformatics methods offers new perspectives for identifying diagnostic and therapeutic targets for complicated forms of HCV and other viral infections. We show how the electron-ion interaction potential (EIIP) amino-acid scale used in the ISM combined with a robust, high performance hydrophobicity scale can provide new insights for understanding protein structure/function and protein-protein interactions. PMID- 27000566 TI - How I Teach Hemi-Arch Replacement. PMID- 27000567 TI - Our New Reality of Public Reporting: Shame Rather Than Blame? PMID- 27000568 TI - Invited Commentary. PMID- 27000569 TI - Invited Commentary. PMID- 27000570 TI - Invited Commentary. PMID- 27000571 TI - Invited Commentary. PMID- 27000572 TI - Invited Commentary. PMID- 27000573 TI - Invited Commentary. PMID- 27000574 TI - Invited Commentary. PMID- 27000575 TI - Emergency Pulmonary Embolectomy Using Minimally Invasive Cardiac Surgery. AB - A 78-year-old man who had undergone operation for acute type A aortic dissection presented with dyspnea and shock. Chest computed tomography revealed pulmonary embolism. Minimally invasive cardiac surgery was performed through a right fourth intercostal skin incision using cardiopulmonary bypass through the right femoral artery and vein. The right pulmonary artery below the superior vena cava was incised vertically, and the thrombus was extracted directly by balloon catheter. The patient was weaned off cardiopulmonary bypass uneventfully. The postoperative course was also uneventful. In redo cardiac surgery, pulmonary embolectomy through minimally invasive right thoracotomy can be easily performed, with quick recovery. PMID- 27000576 TI - Cardiac Sarcoma Arising From Malignant Transformation of a Preexisting Atrial Myxoma. AB - A 49-year-old man presented with shortness of breath on exertion, orthopnea, and chest pain. On transthoracic echocardiography, a myxomatous mass was seen in the left atrium. A diagnosis of atrial myxoma was made and the patient underwent urgent surgical intervention. At operation, the mass, which extended into the anterior leaflet of the mitral valve, was excised. Histopathologic examination showed a primary cardiac sarcoma arising within a preexisting atrial myxoma. The patient received no further treatment and died 7 months postoperatively. We report the first case of a malignant transformation of an atrial myxoma to a cardiac sarcoma. PMID- 27000577 TI - Axillary Artery Cannulation in Acute Aortic Dissection: A Word of Caution. AB - Arterial cannulation into the right axillary artery is a commonly adopted perfusion strategy in the treatment of acute aortic dissection. Here we describe our experience of accidentally cannulating the axillary artery in a case of acute aortic dissection with an aberrant right subclavian artery, which was missed preoperatively because its proximal segment was malperfused by the dissection and thereby not enhanced. The rapid hemodynamics collapse at the start of the bypass was reversed by prompt switching to femoral perfusion. Postoperative follow-up computed tomographic angiography revealed a well-perfused right aberrant subclavian artery. Surgeons should be aware of an aortic arch anomaly whenever performing an axillary artery cannulation. PMID- 27000578 TI - Biventricular Repair of Pulmonary Atresia After Fontan Palliation. AB - Fontan palliation is used when biventricular repair (BVR) is not possible. Early outcomes are acceptable; however, the long-term sequelae include protein-losing enteropathy, declining functional status, increased pulmonary vascular resistance, heart failure, and hepatic and renal dysfunction. These adverse events are characteristic of persistent venous hypertension and may be avoided if restoring biventricular circulation is possible. Arrhythmias are a common adverse event, particularly in patients with an atriopulmonary connection, which may lead to acute decompensation and early death. We describe a 30-year-old woman who underwent successful BVR for pulmonary atresia with intact ventricular septum and demonstrate that where favorable anatomy exists with a failing Fontan, BVR should be considered. PMID- 27000579 TI - Pulmonary Valve Replacement With Balloon-Expandable Prosthesis Under Direct Vision: A Novel Therapeutic Approach. AB - A 57-year-old woman with a history of pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries was referred for a fifth redo sternotomy for right ventricular outflow conduit replacement. Traditional pulmonary valve replacement was aborted during the procedure because of heavy calcification, and the pulmonary valve was replaced with a SAPIEN XT stent valve under direct vision. We believe this is the first application of a balloon expandable stent valve in the pulmonary valve position under direct vision. It provides a novel therapeutic approach to recurrent pulmonary valve dysfunction in adult congenital heart diseases. PMID- 27000580 TI - Uncommon Case of Intrapericardial Nontyphoidal Salmonella Infection in a Preterm Baby Presenting As a Cardiac Tumor. AB - We report a case of an intrapericardial infection resulting from Salmonella Tennessee in a 2-month-old baby, which, upon initial presentation, was masked by a cardiac tumor. The diagnosis was confirmed after successful surgical resection of the mass. Transmission of the infection may have occurred between mother and child in utero, rendering this case extremely unusual. PMID- 27000581 TI - Systolic Anterior Motion Obstructing the Pulmonary Outflow Tract After Tricuspid Valve Replacement. AB - A patient with congenitally corrected transposition of the great arteries who presented with shortness of breath was found to have severe tricuspid regurgitation and right ventricular impairment. After uneventful mechanical systemic tricuspid atrioventricular valve replacement, the patient was extubated within 12 hours. On the first postoperative day, he developed episodes of profound hypotension lasting a few seconds. A transesophageal echocardiogram demonstrated displacement of the interventricular septum that caused systolic anterior motion of the mitral valve into the subpulmonic left ventricle. Mitral valve replacement resolved this complication, and the patient proceeded to do well at discharge. PMID- 27000582 TI - Endoscopic Management of Early Upper Gastrointestinal Bleeding After Minimally Invasive Ivor-Lewis Esophagectomy. AB - Minimally invasive esophagectomy is now accepted as a regular treatment modality for esophageal cancer. Upper gastrointestinal (GI) bleeding is a common postoperative adverse event of esophagectomy. However, there are very few reports in the literature on endoscopic management of early upper GI bleeding after an esophagectomy. Here, we report the successful management of such an early case of GI bleeding after thoracolaparoscopic esophagectomy by the use of endoscopic intrathoracic anastomosis. PMID- 27000583 TI - Minimally Invasive Surgical Repair for Congenital Bronchobiliary Fistula in an Adult. AB - Congenital bronchobiliary fistula (CBBF) is a very rare disease and usually requires surgical intervention at a young age. We report a case of CBBF in an adult who was treated successfully with a minimally invasive endoscopic operation. PMID- 27000584 TI - Thoracic Endovascular Aortic Stent Graft to Facilitate Aortic Resection During Pneumonectomy and Vertebrectomy for Locally Invasive Lung Cancer. AB - Endovascular stent graft placement has been used to facilitate resection of tumors invading the thoracic aorta. Here we describe the first use of an aortic endograft for preoperative protection of the thoracic descending aorta before left pneumonectomy for a primary lung cancer invading the thoracic spine and thoracic descending aorta. PMID- 27000585 TI - Tracheal Resection for Symptomatic Tracheal Stenosis During Pregnancy. AB - A 31-year-old multipara was diagnosed with tracheal stenosis that developed after intubation after an intentional benzodiazepine overdose in the first trimester of pregnancy. Tracheal dilations only temporarily improved her dyspnea at rest. A definitive repair by tracheal resection and reconstruction was performed at 28 weeks' gestation. Her symptoms resolved, and she delivered vaginally at 36 weeks' gestation after spontaneous labor. PMID- 27000586 TI - Tracheal Glomangioleiomyoma Treated by Multimodal Interventional Bronchoscopy. AB - Glomus tumors of the trachea are particularly rare, and their management is usually based on sleeve resection with end-to-end anastomosis. Glomangiomyoma represents the rarest histologic subtype and has been observed only once in the trachea. We describe the first case of tracheal glomangiomyoma treated by multimodal interventional bronchoscopy. PMID- 27000587 TI - Primary Neuroendocrine Carcinoma of the Middle Mediastinum Involving the Right Main Pulmonary Artery. AB - Primary neuroendocrine neoplasms of the mediastinum are extremely rare. We report the case of a 54-year-old woman who presented with dyspnea and was found to have a 6.8-cm tumor completely obliterating the right main pulmonary artery. Analysis of an endobronchial ultrasound fine-needle aspiration revealed a neuroendocrine tumor. A positron emission tomography scan showed no evidence of distant disease. The patient underwent surgical resection with reconstruction of the right main pulmonary artery with a Dacron (DuPont, Wilmington, DE) graft, followed by chemoradiotherapy. We discuss the presentation and management of this patient and review the current treatment options of primary neuroendocrine carcinomas of the mediastinum. PMID- 27000588 TI - Thoracoscopic Resection of a Symptomatic, Congenital Rib Synostosis. AB - We describe a rare case of a 20-year-old man with a 11/2-year history of a symptomatic congenital bridging rib synostosis. A minimally invasive surgical solution was provided, with resolution of symptoms. PMID- 27000589 TI - Complex Tricuspid Valve Repair in Patients With Pacer Defibrillator-Related Tricuspid Regurgitation. AB - Tricuspid valve regurgitation in patients with heart failure or in those undergoing complex cardiac operations is associated with increased morbidity and mortality. We report our results with a technique of repairing the tricuspid valves while retaining the pacer defibrillator lead. Patients had tricuspid valve repairs that included repositioning of the pacer defibrillator lead, approximation of septal and inferior/posterior leaflets in a modified cleft repair, and implantation of a tricuspid annuloplasty ring. This procedure was performed in more than 42 patients with good success. PMID- 27000590 TI - Cox-Maze IV in Total Anomalous Pulmonary Venous Drainage After Sutureless Repair. AB - Modifications of conventional ablation strategies can make arrhythmia surgery more efficient after primary sutureless repair of total anomalous pulmonary venous drainage. We present a surgical technique performed in a 3-year-old patient who experienced ongoing atrial arrhythmia after sutureless repair. A new modified Cox-Maze IV procedure was performed, which respects the special characteristics of patients after sutureless repairs, showing good short-term results. PMID- 27000592 TI - Jack Morton Matloff, MD, March 13, 1933 to August 20, 2015. AB - Jack Morton Matloff, the 35th president of the Society of Thoracic Surgeons, died on August 20, 2015, surrounded by his family. His worldwide contributions to clinical cardiothoracic surgery and his service to the Society of Thoracic Surgeons have had a lasting impact on our specialty. PMID- 27000593 TI - Reply. PMID- 27000594 TI - Defining Measures of Quality in Lung Cancer Diagnosis and Staging. PMID- 27000595 TI - Do Margins Really Affect Prognosis in Wedge Resection for Early-Stage Lung Cancer? PMID- 27000596 TI - Reply. PMID- 27000597 TI - Early Outcomes With Marginal Donor Hearts Compared With Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: Could the Cardiac Allocation Score Be the Solution to the Dilemma of Therapy Selection? PMID- 27000598 TI - Reply. PMID- 27000599 TI - Is Nadir Oxygen Delivery on Cardiopulmonary Bypass an Independent Risk Factor for Acute Kidney Injury After Cardiac Surgery? PMID- 27000600 TI - Reply. PMID- 27000601 TI - Reply. PMID- 27000602 TI - Perioperative Management of Patients with Moyamoya Syndrome: Do All Roads Lead to Rome? PMID- 27000603 TI - Surgeon's Tiredness or Patient's Fasting? What Is More Relevant for Outcome in Nonemergent Cardiac Surgery? PMID- 27000604 TI - Reply. PMID- 27000605 TI - The Role of Intrapericardial Pulmonary Arteries in Patients With PA/VSD/MAPCAs. PMID- 27000606 TI - Reply. PMID- 27000607 TI - Transbrachial Intraaortic Balloon Pumping: The Forgotten Vessel? PMID- 27000608 TI - Reply. PMID- 27000609 TI - Assistant Training Using Videothoracoscopy. PMID- 27000610 TI - Swinging Calcified Amorphous Tumors With Related Mitral Annular Calcification. AB - Among cardiac calcified amorphous tumors, the mitral annular calcification related calcified amorphous tumor is extremely rare. We herein describe 3 surgical cases of swinging calcified amorphous tumor with related mitral annular calcification. The clinical, echocardiographic, and pathophysiologic features are reported here together with a brief review of the literature. PMID- 27000611 TI - Successful Management of Cardiac Arrest Due to Pulmonary Embolus Using Extracorporeal Membrane Oxygenation and Ultrasound-Accelerated Catheter-Directed Thrombolysis. AB - Here we present the case of a patient that suffered a cardiac arrest due to pulmonary embolus. The patient was resuscitated using extracorporeal membrane oxygenation and treated with ultrasound-accelerated catheter-directed thrombolysis during support on extracorporeal membrane oxygenation, with an excellent outcome. This case demonstrates that the use of extracorporeal membrane oxygenation and ultrasound-accelerated catheter-directed thrombolysis can be highly effective for managing select patients with pulmonary embolus and cardiac arrest. PMID- 27000612 TI - Cardiogenic Shock From Coronary Compression: A Difficult Diagnosis But Easy Fix. AB - Two patients experienced compression of a coronary artery bypass graft or native coronary artery by mediastinal drains placed after cardiac surgery. Both events were identified in the catheterization laboratory and resolved after removal of the drains. One patient required concomitant percutaneous thrombectomy of the bypass graft. Although both patients' cardiac function was initially severely impaired, neither patient had permanent cardiac damage and both were successfully discharged home. PMID- 27000613 TI - Diagnostic Value of Contrast-Enhanced Multiphase Computed Tomography for Assessment of Percutaneous Pulmonary Valve Obstruction. AB - Percutaneous pulmonary valve replacement has emerged as an alternative to operation for some patients with congenital heart disease requiring intervention. Endocarditis is increasingly described as an adverse event during follow-up [1 4]. Diagnosis is difficult because of the poor visualization of the prosthetic valve in the pulmonary position by transthoracic and transesophageal echocardiogram and by the metallic artifact that degrades the image quality of magnetic resonance imaging (MRI). Two cases of percutaneous pulmonary valve obstruction diagnosed by cardiac computed tomographic angiography are presented. These cases demonstrate the utility of cardiac computed tomography for noninvasive imaging of suspected thrombus or endocarditis in a percutaneously placed pulmonary valve. PMID- 27000614 TI - Successful Treatment of Invasive Pulmonary Mucormycosis in an Immunocompromised Patient. AB - A 59-year-old man undergoing chemotherapy for acute myelogenous leukemia had a bilateral pneumonic process. The right lung subsequently developed several small cavitary lesions extending from the central hilum to the chest wall. Despite medical therapy, repeat imaging demonstrated coalescence into a single, large, central cavitary lesion. Thoracic surgery was consulted because of the central hilar involvement of all three lobes; a pneumonectomy would have been required to resect the lesion. However, he was not a candidate for pneumonectomy because of a low predicted postoperative forced expiratory volume in 1 second. We performed a rib resection, debridement, and marsupialization, in which the skin was sewn circumferentially to the parietal pleura. His wound was managed with wet-to-dry dressings. Postoperatively, he recovered well, with resolution of his cough. Three weeks after surgery, he was discharged from the hospital, and the cavity completely closed at 4 months. PMID- 27000615 TI - Extralobar Aneurysm of Intralobar Pulmonary Sequestration Artery Originating From Aorta Arch. PMID- 27000616 TI - An Aneurysmal Abdominal Aortic Branch Supplying an Intralobar Pulmonary Sequestration. PMID- 27000617 TI - Tumor Tachycardia. PMID- 27000618 TI - Giant Aneurysm in a Patient With Noncorrected and Longstanding Aortic Coarctation. PMID- 27000619 TI - The "Lantern" Procedure to Simplify Treatment of Retrograde Type A Dissection After Thoracic Endograft Stenting. AB - The emergency repair of retrograde type A aortic dissection after thoracic endovascular aortic repair is a complex and challenging surgical procedure and carries a surgical challenge. Previous studies have reported a significant mortality in the complex repair of retrograde type A aortic dissection after thoracic endovascular aortic repair. We devised a simplified hybrid method-the "Lantern" procedure-to solve this retrograde type A aortic dissection complication. PMID- 27000620 TI - Ductus Arteriosus Banding to Facilitate Stenting During the Hybrid Stage I Procedure. AB - Neonates with hypoplastic left heart syndrome and high-risk factors for an open Norwood procedure may benefit from a hybrid stage I procedure. The presence of a giant patent ductus arteriosus prevents safe deployment of the ductus arteriosus stent. We describe a new technique that involves banding the patent ductus arteriosus, therefore allowing stent implantation during hybrid stage I palliation. PMID- 27000621 TI - Bilateral Giant Coronary Artery Aneurysms Complicated by Acute Coronary Syndrome and Cardiogenic Shock. AB - Giant coronary aneurysms are rare. We present a 25-year-old woman with a known history of non-Kawasaki/nonatherosclerotic bilateral coronary aneurysms. She was transferred to our facility with acute coronary syndrome complicated by cardiogenic shock. Angiography demonstrated giant bilateral coronary aneurysms and complete occlusion of the left anterior descending (LAD) artery. Emergent coronary artery bypass grafting was performed. Coronary artery bypass grafting is the preferred approach for addressing giant coronary aneurysms. Intervention on the aneurysm varies in the literature. Aggressive revascularization is recommended in the non-Kawasaki/nonatherosclerotic aneurysm patient, and ligation should be performed in patients with thromboembolic phenomena. PMID- 27000622 TI - Successful Repair of a Bicuspid Pulmonary Autograft Valve Causing Early Insufficiency After a Ross Procedure. AB - The Ross procedure is an excellent option in terms of long-term outcomes for young patients requiring aortic valve replacement. We report the case of a 49 year-old woman who presented with worsening dyspnea and episodes of presyncope in the context of a patient-prosthesis mismatch, 13 years after mechanical aortic valve replacement. She underwent a Ross procedure despite the pulmonary valve being bicuspid at intraoperative examination. Following implantation, the autograft valve showed an eccentric jet of regurgitation requiring bicuspid valve repair. To our knowledge, this is the first reported case of successful repair of a bicuspid pulmonary autograft valve. PMID- 27000623 TI - Identifying educator behaviours for high quality verbal feedback in health professions education: literature review and expert refinement. AB - BACKGROUND: Health professions education is characterised by work-based learning and relies on effective verbal feedback. However the literature reports problems in feedback practice, including lack of both learner engagement and explicit strategies for improving performance. It is not clear what constitutes high quality, learner-centred feedback or how educators can promote it. We hoped to enhance feedback in clinical practice by distinguishing the elements of an educator's role in feedback considered to influence learner outcomes, then develop descriptions of observable educator behaviours that exemplify them. METHODS: An extensive literature review was conducted to identify i) information substantiating specific components of an educator's role in feedback asserted to have an important influence on learner outcomes and ii) verbal feedback instruments in health professions education, that may describe important educator activities in effective feedback. This information was used to construct a list of elements thought to be important in effective feedback. Based on these elements, descriptions of observable educator behaviours that represent effective feedback were developed and refined during three rounds of a Delphi process and a face-to-face meeting with experts across the health professions and education. RESULTS: The review identified more than 170 relevant articles (involving health professions, education, psychology and business literature) and ten verbal feedback instruments in health professions education (plus modified versions). Eighteen distinct elements of an educator's role in effective feedback were delineated. Twenty five descriptions of educator behaviours that align with the elements were ratified by the expert panel. CONCLUSIONS: This research clarifies the distinct elements of an educator's role in feedback considered to enhance learner outcomes. The corresponding set of observable educator behaviours aim to describe how an educator could engage, motivate and enable a learner to improve. This creates the foundation for developing a method to systematically evaluate the impact of verbal feedback on learner performance. PMID- 27000624 TI - Hoffa's fat pad abnormalities, knee pain and magnetic resonance imaging in daily practice. AB - Hoffa's (infrapatellar) fat pad (HFP) is one of the knee fat pads interposed between the joint capsule and the synovium. Located posterior to patellar tendon and anterior to the capsule, the HFP is richly innervated and, therefore, one of the sources of anterior knee pain. Repetitive local microtraumas, impingement, and surgery causing local bleeding and inflammation are the most frequent causes of HFP pain and can lead to a variety of arthrofibrotic lesions. In addition, the HFP may be secondarily involved to menisci and ligaments disorders, injuries of the patellar tendon and synovial disorders. Patients with oedema or abnormalities of the HFP on magnetic resonance imaging (MRI) are often symptomatic; however, these changes can also be seen in asymptomatic patients. Radiologists should be cautious in emphasising abnormalities of HFP since they do not always cause pain and/or difficulty in walking and, therefore, do not require therapy. Teaching Points * Hoffa's fat pad (HFP) is richly innervated and, therefore, a source of anterior knee pain. * HFP disorders are related to traumas, involvement from adjacent disorders and masses. * Patients with abnormalities of the HFP on MRI are often but not always symptomatic. * Radiologists should be cautious in emphasising abnormalities of HFP. PMID- 27000626 TI - Quaternary Polymer Electrolytes Containing an Ionic Liquid and a Ceramic Filler. AB - In this work, the individual and combined effects of an ionic liquid 1-butyl-1 methylpyrrolidinium bis(trifluoromethanesulfonyl)imide and ceramic filler silicon dioxide on the thermal and electrochemical properties of poly(ethylene oxide) electrolytes have been investigated. The electrolyte containing both components has the lowest glass transition (-60 degrees C) and melting temperatures (27 degrees C), the highest conductivity at any investigated temperature, and the highest limiting current density (at 40 degrees C). This solid polymer electrolyte also exhibits the best long-term cycling performance in Li/LiFePO4 cells. PMID- 27000625 TI - Intermediate filament aggregates cause mitochondrial dysmotility and increase energy demands in giant axonal neuropathy. AB - Intermediate filaments (IFs) are cytoskeletal polymers that extend from the nucleus to the cell membrane, giving cells their shape and form. Abnormal accumulation of IFs is involved in the pathogenesis of number neurodegenerative diseases, but none as clearly as giant axonal neuropathy (GAN), a ravaging disease caused by mutations in GAN, encoding gigaxonin. Patients display early and severe degeneration of the peripheral nervous system along with IF accumulation, but it has been difficult to link GAN mutations to any particular dysfunction, in part because GAN null mice have a very mild phenotype. We therefore established a robust dorsal root ganglion neuronal model that mirrors key cellular events underlying GAN. We demonstrate that gigaxonin is crucial for ubiquitin-proteasomal degradation of neuronal IF. Moreover, IF accumulation impairs mitochondrial motility and is associated with metabolic and oxidative stress. These results have implications for other neurological disorders whose pathology includes IF accumulation. PMID- 27000627 TI - Apple intake and cancer risk: a systematic review and meta-analysis of observational studies. AB - OBJECTIVE: Conflicting results on the association between fruit consumption and cancer risk have been reported. Little is known about the cancer preventive effects of different fruit types. The present meta-analysis investigates whether an association exists between apple intake and cancer risk. DESIGN: Relevant observational studies were identified by literature search (PubMed, Web of Science and Embase). A random-effect model was used to estimate the cancer risk in different anatomical sites. Between-study heterogeneity and publication bias were assessed using adequate statistical tests. RESULTS: Twenty case-control (three on lung, five on colorectal, five on breast, two on oesophageal, three on oral cavity, two on prostate and one each on pancreas, bladder, larynx, ovary, kidney and brain cancer) and twenty-one cohort (seven on lung, two on colorectal, three on breast and one each on oesophageal, pancreas, bladder, kidney, endometrial, head-neck, urothelial and stomach cancer) studies met the inclusion criteria. Comparing the highest v. lowest level of apple consumption, the reduction of lung cancer risk was statistically highly significant in both case control (OR=0.75; 95% CI 0.63, 0.88; P=0.001, I 2=0 %) and cohort studies (relative risk=0.89; 95% CI 0.84, 0.94; P<0.001, I 2=53 %). Instead, in the case of colorectal (OR=0.66; 95% CI 0.54, 0.81; P<0.001, I 2=55%), breast (OR=0.79; 95% CI 0.73, 0.87; P<0.001, I 2=1 %) and overall digestive tract (OR=0.50; 95% CI 0.36, 0.69; P<0.001, I 2=90 %) cancers a significant preventive effect of apples was found only in case-control studies while prospective studies indicated no effect. No evidence of publication bias could be detected for colorectal, oral cavity, oesophageal and breast cancer. However, some confounding effects may be present and related to the consumption of other fruit which have not been considered as adjusting factors. CONCLUSIONS: The present meta-analysis indicates that consumption of apples is associated with a reduced risk of cancer in different anatomical sites. PMID- 27000628 TI - "Liquid Knife" to Fabricate Patterning Single-Crystalline Perovskite Microplates toward High-Performance Laser Arrays. AB - A facile and effective "liquid knife" is created by controlling the dewetting process of the liquid precursor, yielding patterning single-crystalline perovskite microplates with uniform size, precise positioning, high quality, and low lasing thresholds. The sizes and location of single-crystalline perovskite are controllable, leading to mode-tunable lasing emission and patterned lasers. PMID- 27000630 TI - The use of SESK as a trend parameter for localized bearing fault diagnosis in induction machines. AB - A critical work of bearing fault diagnosis is locating the optimum frequency band that contains faulty bearing signal, which is usually buried in the noise background. Now, envelope analysis is commonly used to obtain the bearing defect harmonics from the envelope signal spectrum analysis and has shown fine results in identifying incipient failures occurring in the different parts of a bearing. However, the main step in implementing envelope analysis is to determine a frequency band that contains faulty bearing signal component with the highest signal noise level. Conventionally, the choice of the band is made by manual spectrum comparison via identifying the resonance frequency where the largest change occurred. In this paper, we present a squared envelope based spectral kurtosis method to determine optimum envelope analysis parameters including the filtering band and center frequency through a short time Fourier transform. We have verified the potential of the spectral kurtosis diagnostic strategy in performance improvements for single-defect diagnosis using real laboratory collected vibration data sets. PMID- 27000631 TI - Finite-time tracking control of nth-order chained-form non-holonomic systems in the presence of disturbances. AB - This paper addresses the problem of finite-time tracking controller design for nth-order chained-form non-holonomic systems in the presence of unknown disturbances. To this aim, a generalized disturbance observer based controller is proposed and combined with a recursive terminal sliding mode approach which guarantees finite-time convergence of the disturbance observer dynamic. By introducing a time-varying transformation and introducing a new control law, the existence of the sliding around the recursive terminal sliding mode surfaces is guaranteed. Finally, the proposed approach is applied for a wheeled mobile robot with a fourth-order chained-form non-holonomic model. The simulation results demonstrate the desirable and robust tracking performance of the proposed approach in the presence of unknown disturbance. PMID- 27000632 TI - Performance analysis of fractional order extremum seeking control. AB - Extremum-seeking scheme is a powerful adaptive technique to optimize steady-state system performance. In this paper, a novel extremum-seeking scheme for the optimization of nonlinear plants using fractional order calculus is proposed. The fractional order extremum-seeking algorithm only utilizes output measurements of the plant, however, it performs superior in many aspects such as convergence speed and robustness. A detailed stability analysis is given to not only guarantee a faster convergence of the system to an adjustable neighborhood of the optimum but also confirm a better robustness for proposed algorithm. Furthermore, simulation and experimental results demonstrate that the fractional order extremum-seeking scheme for nonlinear systems outperforms the traditional integer order one. PMID- 27000633 TI - Heavy metal accumulation in Lacistorhynchus dollfusi (Trypanorhyncha: Lacistorhynchidae) infecting Citharichthys sordidus (Pleuronectiformes: Bothidae) from Santa Monica Bay, Southern California. AB - The accumulation of heavy metals in macroparasites of fish has been widely studied in freshwater environments. Less is known about metal uptake in cestodes parasitizing marine fish. Lacistorhynchus dollfusi is a common larval cestode parasite of Pacific sanddab (Citharichthys sordidus), a flatfish species inhabiting Santa Monica Bay. The ability of this cestode to concentrate metals in its tissues was compared with metal levels in its sanddab host. Fish and cestode tissue were analysed for 14 elements using Inductively Coupled Plasma Mass Spectrometry. The elements analysed were silver (Ag), arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), potassium (K), lead (Pb), rubidium (Rb), selenium (Se), strontium (Sr), titanium (Ti) and zinc (Zn). Three of the 14 metals (Cu, Hg and Zn) were significantly greater in concentration in L. dollfusi compared with their levels in the liver, intestine and muscle of their fish host. They ranked in concentration from highest to lowest as follows: Zn > Cu > Hg. The ability of the cestode L. dollfusi to uptake metals at higher concentrations than its host warrants its consideration as a candidate for a heavy metal accumulation indicator of pollution exposure in Pacific sanddab. PMID- 27000634 TI - Angiostrongylus vasorum in the eye: new case reports and a review of the literature. AB - BACKGROUND: Nematodes of the genus Angiostrongylus are important causes of potentially life-threatening diseases in several animal species and humans. Angiostrongylus vasorum affects the right ventricle of the heart and the pulmonary arteries in dogs, red foxes and other carnivores. The diagnosis of canine angiostrongylosis may be challenging due to the wide spectrum of clinical signs. Ocular manifestations have been seldom reported but have serious implications for patients. METHODS: The clinical history of three cases of infection with A. vasorum in dogs diagnosed in UK, France and Italy, was obtained from clinical records provided by the veterinary surgeons along with information on the diagnostic procedures and treatment. Nematodes collected from the eyes of infected dogs were morphologically identified to the species level and molecularly analysed by the amplification of the nuclear 18S rRNA gene. RESULTS: On admission, the dogs were presented with various degrees of ocular discomfort and hyphema because of the presence of a motile object in the eye. The three patients had ocular surgery during which nematodes were removed and subsequently morphologically and molecularly identified as two adult males and one female of A. vasorum. CONCLUSIONS: Three new cases of canine ocular angiostrongylosis are reported along with a review of other published clinical cases to improve the diagnosis and provide clinical recommendation for this parasitic condition. In addition, the significance of migratory patterns of larvae inside the host body is discussed. Veterinary healthcare workers should include canine angiostrongylosis in the differential diagnosis of ocular diseases. PMID- 27000635 TI - Is it possible to reverse aged acetylcholinesterase inhibited by organophosphorus compounds? Insight from the theoretical study. AB - The main treatment for organophosphorus (OP) compound poisoning in clinics is to restore the activity of acetylcholinesterase (AChE) through oxime-induced reactivation of the phosphorylated OP-AChE adduct. It suffers from a competitive and irreversible aging reaction of the phosphorylated OP-AChE adduct, resulting in permanent inactivity of AChE. However, it was recently reported that N-methyl 2-methoxypyridinium species can act as methylating agents to methylate the methyl methane-phosphonate monoanion, in which the reaction mimics the reverse of the aging reaction of the phosphorylated OP-AChE adduct. If the aging reaction could be really reversed, the efficiency for the OP detoxification should be significantly improved, bringing up the possibility to develop an agent to reverse the aging process of the phosphorylated OP-AChE adduct. However, such a reaction with the N-methyl-2-methoxypyridinium species in the enzyme is still not reported so far. It is of great interest to know whether or not this reaction is observable in the enzyme, and more importantly, if it turns out to be not observable in the enzyme, why such a reaction proceeds quickly in aqueous solution but not in the enzyme. In the present study, we performed DFT calculations and quantum mechanical/molecular mechanical (QM/MM) calculations to reveal the fundamental mechanism for the methylation of both the methyl methane phosphonate monoanion and the aged sarin-AChE adduct by N-methyl-2 methoxypyridinium species, respectively. The obtained results support the SN2 reaction mechanism, not the stepwise mechanism, for the methylation of the methyl methane-phosphonate monoanion by 9 reported N-methyl-2-methoxypyridinium compounds. The calculated free energy barriers are in good agreement with the experimental data. The methylation of the aged sarin-AChE adduct by one N-methyl 2-methoxypyridinium compound (labeled as compound 2) also employs the SN2 reaction mechanism with an extremely high free energy barrier of 30.4 +/- 3.5 (or 26.6) kcal mol(-1), implying that this reaction in the enzyme hardly occurs. Our results clearly show that compound 2 forms a strong pi-pi stacking interaction with the aromatic ring of the W86 residue of AChE, making itself unable to approach sarin for the reverse of the aging process. On the basis of the structure and mechanism, several possible strategies have been suggested for designing methylating agents with higher activity against the aged sarin-AChE adduct. PMID- 27000636 TI - Suboptimal identification of patient-specific risk factors for poor wound healing can be improved by simple interventions. AB - Poor wound healing is an important surgical complication. At-risk wounds must be identified early and monitored appropriately. Wound surveillance is frequently inadequate, leading to increased rates of surgical site infections (SSIs). Although the literature demonstrates that risk factor identification reduces SSI rates, no studies have focused on wound management at a junior level. Our study assesses documentation rates of patient-specific risk factors for poor wound healing at a large district general hospital in the UK. It critically evaluates the efficacy of interventions designed to promote surveillance of high-risk wounds. We conducted a full-cycle clinical audit examining medical records of patients undergoing elective surgery over 5 days. Interventions included education of the multidisciplinary team and addition of a Wound Healing Risk Assessment (WHRA) checklist to surgical admissions booklets. This checklist provided a simple stratification tool for at-risk wounds and recommendations for escalation. Prior to interventions, the documentation of patient-specific risk factors ranged from 0.0% to 91.7% (mean 42.6%). Following interventions, this increased to 86.4-95.5% (mean 92.5%), a statistically significant increase of 117.1% (P < 0.01). This study demonstrates that documentation of patient-specific risk factors for poor wound healing is inadequate. We have shown the benefit of introducing interventions to increase risk factor awareness. PMID- 27000637 TI - Optical micro-tomography "OPenT" allows the study of large toadfish Halobatrachus didactylus embryos and larvae. AB - Batrachoidids, which include midshipman and toadfish are less known among embryologists, but are common in other fields. They are characteristic for their acoustic communication, and develop hearing and sound production while young juveniles. They lay large benthic eggs (>5mm) with a thick chorion and adhesive disk and slow development, which are particularly challenging for studying embryology. Here we took advantage of a classical tissue clearing technique and the OPenT open-source platform for optical tomography imaging, to image a series of embryos and larvae from 3 to 30mm in length, which allowed detailed 3D anatomical reconstructions non-destructively. We documented some of the developmental stages (early and late in development) and the anatomy of the delicate stato-acoustic organs, swimming bladder and associated sonic muscles. Compared to other techniques accessible to developmental biology labs, OPenT provided advantages in terms of image quality, cost of operation and data throughput, allowing identification and quantitative morphometrics of organs in larvae, earlier and with higher accuracy than is possible with other imaging techniques. PMID- 27000638 TI - Mesoderm patterning and morphogenesis in the polychaete Alitta virens (Spiralia, Annelida): Expression of mesodermal markers Twist, Mox, Evx and functional role for MAP kinase signaling. AB - Mesoderm represents the evolutionary youngest germ layer and forms numerous novel tissues in bilaterian animals. Despite the established conservation of the gene regulatory networks that drive mesoderm differentiation (e.g. myogenesis), mechanisms of mesoderm specification are highly variable in distant model species. Thus, broader phylogenetic sampling is required to reveal common features of mesoderm formation across bilaterians. Here we focus on a representative of Spiralia, the marine annelid Alitta virens, whose mesoderm development is still poorly investigated on the molecular level. We characterize three novel early mesodermal markers for A. virens - Twist, Mox, and Evx - which are differentially expressed within the mesodermal lineages. The Twist mRNA is ubiquitously distributed in the fertilized egg and exhibits specific expression in endomesodermal- and ectomesodermal-founder cells at gastrulation. Twist is expressed around the blastopore and later in a segmental metameric pattern. We consider this expression to be ancestral, and in support of the enterocoelic hypothesis of mesoderm evolution. We also revealed an early pattern of the MAPK activation in A. virens that is different from the previously reported pattern in spiralians. Inhibition of the MAPK pathway by U0126 disrupts the metameric Twist and Mox expression, indicating an early requirement of the MAPK cascade for proper morphogenesis of endomesodermal tissues. PMID- 27000639 TI - POSTTRAUMATIC STRESS SYMPTOMS AND AVERSION TO AMBIGUOUS LOSSES IN COMBAT VETERANS. AB - BACKGROUND: Psychiatric symptoms typically cut across traditional diagnostic categories. In order to devise individually tailored treatments, there is a need to identify the basic mechanisms that underlie these symptoms. Behavioral economics provides a framework for studying these mechanisms at the behavioral level. Here, we utilized this framework to examine a widely ignored aspect of trauma-related symptomatology-individual uncertainty attitudes-in combat veterans with and without posttraumatic stress disorder (PTSD). METHODS: Fifty-seven combat veterans, including 30 with PTSD and 27 without PTSD, completed a risk and ambiguity decision-making task that characterizes individual uncertainty attitudes, distinguishing between attitudes toward uncertain outcomes with known ("risk") and unknown ("ambiguity") probabilities, and between attitudes toward uncertain gains and uncertain losses. Participants' choices were used to estimate risk and ambiguity attitudes in the gain and loss domains. RESULTS: Veterans with PTSD were more averse to ambiguity, but not risk, compared to veterans without PTSD, when making choices between possible losses, but not gains. The degree of aversion was associated with anxious arousal (e.g., hypervigilance) symptoms, as well as with the degree of combat exposure. Moreover, ambiguity attitudes fully mediated the association between combat exposure and anxious arousal symptoms. CONCLUSIONS: These results provide a foundation for prospective studies of the causal association between ambiguity attitudes and trauma-related symptoms, as well as etiologic studies of the neural underpinnings of these behavioral outcomes. More generally, these results demonstrate the potential of neuroeconomic and behavioral economic techniques for devising objective and incentive-compatible diagnostic tools, and investigating the etiology of psychiatric disorders. PMID- 27000640 TI - Recent Development of Advanced Materials with Special Wettability for Selective Oil/Water Separation. AB - The increasing number of oil spill accidents have a catastrophic impact on our aquatic environment. Recently, special wettable materials used for the oil/water separation have received significant research attention. Due to their opposing affinities towards water and oil, i.e., hydrophobic and oleophilic, or hydrophilic and oleophobic, such materials can be used to remove only one phase from the oil/water mixture, and simultaneously repel the other phase, thus achieving selective oil/water separation. Moreover, the synergistic effect between the surface chemistry and surface architecture can further promote the superwetting behavior, resulting in the improved separation efficiency. Here, recently developed materials with special wettability for selective oil/water separation are summarized and discussed. These materials can be categorized based on their oil/water separating mechanisms, i.e., filtration and absorption. In each section, representative studies will be highlighted, with emphasis on the materials wetting properties and innovative aspects. Finally, challenges and future research directions in this emerging and promising research field will be briefly described. PMID- 27000641 TI - Severe Cerebral Venous and Sinus Thrombosis: Clinical Course, Imaging Correlates, and Prognosis. AB - BACKGROUND: Severe cerebral venous-sinus thrombosis (CVT) is a rare disease, and its clinical course, imaging correlates, as well as long-term prognosis have not yet been investigated systematically. METHODS: Multicenter retrospective study. Inclusion criteria were CVT, Glasgow coma scale <=9, and treatment in the intensive care unit. Primary outcome was death or dependency, assessed by a modified Rankin Score (mRS) >2 at last follow-up. RESULTS: 114 patients were included. At last follow-up (median 2.5 years), 38 patients (33.3 %) showed no or minor residual symptoms (mRS = 0 or 1), 12 (10.5 %) had a mild (mRS = 2), 13 (11.4 %) a moderate (mRS = 3), 12 (10.5 %) a severe disability (mRS = 4 or 5), and 39 (34.2 %) had died. In bivariate analysis, predictors of poor outcome were any signs of mass effect on imaging, clinical deterioration after admission, and age. In contrast, clinical symptoms on admission and parenchymal lesions per se, such as edema, infarction, or hemorrhage were not predictive. Multivariate predictors of poor outcome were an increase in National Institutes of Health Stroke Scale >=3 after admission [odds ratio (OR) 6.7], bilateral motor signs in the further course (OR 9.2), and midline shift (OR 5.1). CONCLUSION: The outcome of severe CVT is almost equally divided between severe impairment or death and survival with no or only mild handicap. Specifically, space-occupying mass effect and associated neurologic deterioration seem to determine a poor outcome. Therefore, early detection and treatment of mass effect should be the focus of critical care. PMID- 27000642 TI - Headache and Its Approach in Today's NeuroIntensive Care Unit. AB - Headache is a very common symptom in the neurointensive care unit (neuroICU). While headache in the neuroICU can be caused by worsening of a pre-existing primary headache disorder, most are secondary to another condition. Additionally, headache can be the presenting symptom of a number of conditions requiring prompt recognition and treatment including subarachnoid hemorrhage, ischemic and hemorrhagic stroke, central nervous system infection, pituitary apoplexy, and cerebral vasoconstriction. The neuroICU also has a unique postoperative population in which postcraniectomy and postcraniotomy headache, postintravascular intervention headache, hyperperfusion syndrome, ventriculitis, medication overuse or withdrawal headache, and hypercapnia may be encountered. Management varies dramatically depending on the etiology of the headache. Overreliance on opiate analgesics may produce significant adverse effects and lengthen ICU stays. However, nonnarcotic medications are increasingly being recognized as helpful in reducing the pain among various postsurgical and headache patients. Taken together, a multimodal approach targeting the underlying pathology and choosing appropriate systemic and local analgesic medications may be the best way to manage headache in critically ill patients. PMID- 27000643 TI - A Propensity Score-Matched Study of the Use of Non-steroidal Anti-inflammatory Agents Following Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Inflammation may contribute to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Here, we compared outcomes among propensity score matched cohorts who did and did not receive non-steroidal anti-inflammatory drug (NSAID) use after aSAH. METHODS: Propensity score-matched analysis of 413 subjects enrolled in the Clazosentan to Overcome Neurological iSChemia and Infarction OccUring after Subarachnoid hemorrhage (CONSCIOUS-1) study. Propensity score matching was performed on the basis of age, sex, baseline National Institutes of Health Stroke Scale score, World Federation of Neurological Societies grade on admission, procedure used for securing aneurysm, and SAH clot burden. RESULTS: 178 patients were matched (89 received NSAIDs, 89 did not). Propensity score matching was considered acceptable. Patients who had received NSAIDs during their hospital stay had significantly lower mortality rate, and reduced duration of intensive care unit stay and total length of hospital stay (P = 0.035, P = 0.009, and P = 0.053, respectively). At 6 weeks, 80.9 % of patients treated with NSAIDs had good functional outcome compared to 68.5 % of matched controls (P = 0.083). There was no significant difference in the proportions of patients who developed delayed ischemic neurological deficits, angiographic vasospasm, or required rescue therapy. CONCLUSIONS: Inflammation may play a crucial role in the poor outcomes after SAH, and that NSAIDs may be a useful therapeutic option, once validated by larger prospective studies. PMID- 27000644 TI - Evolution and characterization of a new reversibly photoswitching chromogenic protein, Dathail. AB - We report the engineering of a new reversibly switching chromogenic protein, Dathail. Dathail was evolved from the extremely thermostable fluorescent proteins thermal green protein (TGP) and eCGP123 using directed evolution and ratiometric sorting. Dathail has two spectrally distinct chromogenic states with low quantum yields, corresponding to absorbance in a ground state with a maximum at 389nm, and a photo-induced metastable state with a maximum at 497nm. In contrast to all previously described photoswitchable proteins, both spectral states of Dathail are non-fluorescent. The photo-induced chromogenic state of Dathail has a lifetime of ~50min at 293K and pH7.5 as measured by UV-Vis spectrophotometry, returning to the ground state through thermal relaxation. X-ray crystallography provided structural insights supporting a change in conformation and coordination in the chromophore pocket as being responsible for Dathail's photoswitching. Neutron crystallography, carried out for the first time on a protein from the green fluorescent protein family, showed a distribution of hydrogen atoms revealing protonation of the chromophore 4-hydroxybenzyl group in the ground state. The neutron structure also supports the hypothesis that the photo-induced proton transfer from the chromophore occurs through water-mediated proton relay into the bulk solvent. Beyond its spectroscopic curiosity, Dathail has several characteristics that are improvements for applications, including low background fluorescence, large spectral separation, rapid switching time, and the ability to switch many times. Therefore, Dathail is likely to be extremely useful in the quickly developing fields of imaging and biosensors, including photochromic Forster resonance energy transfer, high-resolution microscopy, and live tracking within the cell. PMID- 27000645 TI - Pneumococcal infection is associated with relatively marked peripheral blood leukocytosis. PMID- 27000646 TI - Saving or Subordinating Life? Popular Views in Israel and Germany of Donor Siblings Created through PGD. AB - To explore how cultural beliefs are reflected in different popular views of pre implantation genetic diagnosis for human leukocyte antigen match (popularly known as "savior siblings"), we compare the reception and interpretations, in Germany and Israel, of the novel/film My Sister's Keeper. Qualitative analysis of reviews, commentaries and posts is used to classify and compare normative assessments of PGD for HLA and how they reproduce, negotiate or oppose the national policy and its underlying cultural and ethical premises. Four major themes emanated from the comparison: loss of self-determination and autonomy; loss of dignity through instrumentalization; eugenics and euthanasia; and saving life. In both countries, most commentaries represented a dominant position, with a few negotiated positions. We also highlight the decoding of a relatively less explored bioethical aspect of My Sister's Keeper's narrative, namely the meaning of euthanasia. We conclude by discussing how the findings relate to attempts of providing cultural explanations for the regulation of HLA-PGD. PMID- 27000647 TI - Beyond the skeleton: the role of vitamin D in companion animal health. AB - While the role of vitamin D in the maintenance of skeletal health has been well established for many years, the discovery that many non-skeletal tissues express the vitamin D receptor stimulated renewed interest in vitamin D and its wider physiological roles. Subsequently, a vast literature has emerged over the past three decades which has linked vitamin D deficiency to the development of many human diseases including cancer, autoimmune, infectious and cardiovascular disorders. In contrast, the role vitamin D plays in the physiology of non skeletal tissues in cats and dogs has received little attention. The situation is now starting to change with the publication of several studies that have indicated that vitamin D metabolism is deranged in numerous companion animal disorders. This article reviews the biology of vitamin D in companion animals and highlights some of the recent studies which have advanced understanding of vitamin D homeostasis in cats and dogs. Finally, the essay discusses how a "One Health" approach could further the understanding of vitamin D metabolism in mammals. Investigating vitamin D homoeostasis in companion animals offers many advantages compared to human studies in which vitamin D status is influenced by many more variables. PMID- 27000648 TI - An evaluation of a target-controlled infusion of propofol or propofol-alfentanil admixture for sedation in dogs. AB - OBJECTIVES: To evaluate sedation quality and cardiorespiratory variables in dogs sedated using a target-controlled infusion of propofol or propofol-alfentanil admixture. METHODS: A total of 60 dogs undergoing diagnostic imaging were randomly assigned to one of three sedation protocols: propofol alone; propofol with a low concentration of 12 ug of alfentanil per mL of propofol; or propofol with a higher concentration of 24 ug of alfentanil per mL of propofol. Target controlled infusion was initiated at a propofol target concentration of 1.5 ug/mL and increased until lateral recumbency was achieved. Times to adopt lateral recumbency and recover, pulse rate, respiratory rate, oscillometric mean arterial pressure and oxygen saturation were recorded. Quality of sedation onset and recovery were scored. RESULTS: Propofol target at lateral recumbency differed significantly (P=0.01) between groups with median (range) values of 3.0 (1.5 to 5.5), 2.0 (2 to 4.5) and 2.25 (1.5 to 3.5) ug/mL for propofol alone, propofol with the lower concentration of alfentanil and propofol with the higher concentration of alfentanil groups, respectively. Time to lateral recumbency was longer and quality of onset less smooth for the propofol group. Pulse rate change differed significantly (P<0.001) between groups (mean pulse rate change at onset of sedation: propofol group +2 +/-24 bpm, low concentration alfentanil group -30 +/-24 bpm, higher concentration alfentanil group -26 +/-23 bpm). Hypoxaemia (SpO2 <90%) occurred in 1, 3 and 13 dogs, in the propofol group, the low concentration alfentanil group and the higher concentration of alfentanil group, respectively (P<0.001). CLINICAL SIGNIFICANCE: Addition of alfentanil to propofol target controlled infusion did not confer cardiovascular benefits and, at the higher concentration, alfentanil increased the incidence of hypoxaemia. PMID- 27000649 TI - Systematic review of the prevalence, risk factors, diagnosis and management of meniscal injury in dogs: Part 2. AB - OBJECTIVE: To systematically evaluate the evidence reporting the diagnosis and management of meniscal injury in dogs with cranial cruciate ligament failure. STUDY DESIGN: Systematic literature review. MATERIALS AND METHODS: Research questions relating to the accuracy of diagnostic techniques for meniscal injury and the effects of meniscal treatment were defined. An electronic database search of PubMed and CAB Abstracts was performed during March 2015. Data were extracted for study participants, design, intervention, outcome measures and results. Studies were evaluated using a validated instrument for assessing methodological quality and assigned a Quality Index score. A level of evidence was then assigned to each study. RESULTS: Eighty-nine studies were identified. The median Quality Index score was 14 out of a possible 26. Twenty-seven studies were prospective case series, 31 retrospective case series, 16 animal research and 15 cadaveric studies. There were no class I or class II studies, 27 class III and 62 class IV studies. CONCLUSIONS: Despite a large number of publications the quality of evidence was generally low. No one study or combination of studies provided high quality evidence to support one diagnostic or surgical intervention over another for meniscal injuries in dogs with cranial cruciate ligament failure. PMID- 27000650 TI - Computed tomographic excretory urography features of intramural ectopic ureters in 10 dogs. AB - OBJECTIVES: To describe the morphologic and morphometric computed tomographic excretory urography features of intramural ectopic ureters in dogs. METHODS: Retrospective evaluation of computed tomographic excretory urography studies in 10 dogs with surgical and/or cystoscopically confirmed intramural ectopic ureters. All studies were assessed for ureteral ectopia, dilatation, tortuosity, ureterovesicular junction morphology and ureteral orifice location. RESULTS: A total of 14 intramural ectopic ureters were confirmed at surgery/cystoscopy with reviewers correctly identifying 100% (14/14). Abnormalities on computed tomographic excretory urography included ureteral dilatation (7), ureteral tortuosity (3), lack of a normal ureterovesicular junction (14), urethral ureteral orifice location (14) and lack of ureteral divergence (14). CLINICAL SIGNIFICANCE: Lack of a normal ureterovesicular junction, a urethral-ureteral orifice location and lack of ureteral divergence are common computed tomographic excretory urography findings in dogs with intramural ectopic ureters. This technique requires further investigation to determine whether it might allow differentiation of intramural and extramural ectopic ureters. PMID- 27000651 TI - Acute change in neurological level following canine intervertebral disc herniation. PMID- 27000652 TI - RELN and VLDLR mutations underlie two distinguishable clinico-radiological phenotypes. AB - Pontocerebellar hypoplasias (PCH) are characterized by lack of development and/or early neurodegeneration of cerebellum and brainstem. We report five patients referred for PCH, showing atypical clinical and magnetic resonance imaging (MRI) features suggestive of defects in the Reelin pathway. We screened for mutations in RELN or VLDLR and compared the phenotype of these patients with that of previously reported patients. All patients had profound cerebellar hypoplasia on MRI with peculiar cerebellar morphology, associated with flattened pons and neocortical abnormalities. Patient 1 had profound motor and intellectual disability with moderate lissencephaly suggestive of RELN mutations and was shown to harbor a splicing homozygous RELN mutation. The four other patients had a milder phenotype consistent with CARMQ1 (cerebellar ataxia and mental retardation with or without quadrupedal locomotion). These patients showed mild simplification or thickening of cortical gyration and had VLDLR mutations. Reelin signaling regulates neuronal migration in the developing mammalian brain. VLDLR is a key component of the Reelin pathway. Our patients had a very small and dysplatic cerebellar vermis that should suggest the involvement of these genes. Moreover, differences in clinical severity, involvement of the cerebellar hemispheres, together with the severity of the neocortical defect, enables RELN mutated patients to be distinguished from VLDLR-mutated patients. PMID- 27000653 TI - Characterization of Highly Oxidized Molecules in Fresh and Aged Biogenic Secondary Organic Aerosol. AB - In this work, highly oxidized multifunctional molecules (HOMs) in fresh and aged secondary organic aerosol (SOA) derived from biogenic precursors are characterized with high-resolution mass spectrometry. Fresh SOA was generated by mixing ozone with a biogenic precursor (beta-pinene, limonene, alpha-pinene) in a flow tube reactor. Aging was performed by passing the fresh SOA through a photochemical reactor where it reacted with hydroxyl radicals. Although these aerosols were as a whole not highly oxidized, molecular analysis identified a significant number of HOMs embedded within it. HOMs in fresh SOA consisted mostly of monomers and dimers, which is consistent with condensation of extremely low volatility organic compounds (ELVOCs) that have been detected in the gas phase in previous studies and linked to SOA particle formation. Aging caused an increase in the average number of carbon atoms per molecule of the HOMs, which is consistent with particle phase oxidation of (less oxidized) oligomers already existing in fresh SOA. HOMs having different combinations of oxygen-to-carbon ratio, hydrogen-to-carbon ratio and average carbon oxidation state are discussed and compared to low volatility oxygenated organic aerosol (LVOOA), which has been identified in ambient aerosol based on average elemental composition but not fully understood at a molecular level. For the biogenic precursors and experimental conditions studied, HOMs in fresh biogenic SOA have molecular formulas more closely resembling LVOOA than HOMs in aged SOA, suggesting that aging of biogenic SOA is not a good surrogate for ambient LVOOA. PMID- 27000654 TI - Zbtb20 promotes astrocytogenesis during neocortical development. AB - Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiated astrocytes. However, astrocyte specification occurs before GFAP expression and essential factors for the specification step have remained elusive. Here we show that Zbtb20 regulates astrocyte specification in the mouse neocortex. Zbtb20 is highly expressed in late-stage NPCs and their astrocytic progeny. Overexpression and knockdown of Zbtb20 promote and suppress astrocytogenesis, respectively, although Zbtb20 does not directly activate the Gfap promoter. Astrocyte induction by Zbtb20 is suppressed by knockdown of Sox9 or NFIA. Furthermore, in the astrocyte lineage, Zbtb20 directly represses the expression of Brn2, which encodes a protein necessary for upper-layer neuron specification. Zbtb20 is thus a key determinant of astrocytogenesis, in which it collaborates with Sox9 and NFIA, and acts in part through direct repression of Brn2 expression. PMID- 27000655 TI - Opposing effects of oxidative challenge and carotenoids on antioxidant status and condition-dependent sexual signalling. AB - Several recent hypotheses consider oxidative stress to be a primary constraint ensuring honesty of condition-dependent carotenoid-based signalling. The key testable difference between these hypotheses is the assumed importance of carotenoids for redox homeostasis, with carotenoids being either antioxidant, pro oxidant or unimportant. We tested the role of carotenoids in redox balance and sexual signalling by exposing adult male zebra finches (Taeniopygia guttata) to oxidative challenge (diquat dibromide) and manipulating carotenoid intake. As the current controversy over the importance of carotenoids as antioxidants could stem from the hydrophilic basis of commonly-used antioxidant assays, we used the novel measure of in vivo lipophilic antioxidant capacity. Oxidative challenge reduced beak pigmentation but elicited an increase in antioxidant capacity suggesting resource reallocation from signalling to redox homeostasis. Carotenoids counteracted the effect of oxidative challenge on lipophilic (but not hydrophilic) antioxidant capacity, thereby supporting carotenoid antioxidant function in vivo. This is inconsistent with hypotheses proposing that signalling honesty is maintained through either ROS-induced carotenoid degradation or the pro-oxidant effect of high levels of carotenoid-cleavage products acting as a physiological handicap. Our data further suggest that assessment of lipophilic antioxidant capacity is necessary to fully understand the role of redox processes in ecology and evolution. PMID- 27000656 TI - Selection of suitable reference genes for gene expression studies in Staphylococcus capitis during growth under erythromycin stress. AB - Accurate and reproducible measurement of gene transcription requires appropriate reference genes, which are stably expressed under different experimental conditions to provide normalization. Staphylococcus capitis is a human pathogen that produces biofilm under stress, such as imposed by antimicrobial agents. In this study, a set of five commonly used staphylococcal reference genes (gyrB, sodA, recA, tuf and rpoB) were systematically evaluated in two clinical isolates of Staphylococcus capitis (S. capitis subspecies urealyticus and capitis, respectively) under erythromycin stress in mid-log and stationary phases. Two public software programs (geNorm and NormFinder) and two manual calculation methods, reference residue normalization (RRN) and relative quantitative (RQ), were applied. The potential reference genes selected by the four algorithms were further validated by comparing the expression of a well-studied biofilm gene (icaA) with phenotypic biofilm formation in S. capitis under four different experimental conditions. The four methods differed considerably in their ability to predict the most suitable reference gene or gene combination for comparing icaA expression under different conditions. Under the conditions used here, the RQ method provided better selection of reference genes than the other three algorithms; however, this finding needs to be confirmed with a larger number of isolates. This study reinforces the need to assess the stability of reference genes for analysis of target gene expression under different conditions and the use of more than one algorithm in such studies. Although this work was conducted using a specific human pathogen, it emphasizes the importance of selecting suitable reference genes for accurate normalization of gene expression more generally. PMID- 27000657 TI - Two novel copy number variations involving the alpha-globin gene cluster on chromosome 16 cause thalassemia in two Chinese families. AB - Copy number variations (CNVs) can cause many genetic disorders and the structure analysis of unknown CNVs is important for clinical diagnosis. The human alpha globin gene cluster lies close to the telomere of the short arm on chromosome 16. Copy number variations of this region produce excessive or insufficient alpha globin chains which imbalances the beta-globin chains, resulting in thalassemia. However, these CNVs usually cannot be precisely defined by traditional methods. Here, we designed a technique strategy and applied it to identify two CNVs involving the alpha-globin gene cluster causing thalassemia in two Chinese families. A novel 282 kb duplication (alphaalphaalphaalpha(282)) was identified in family A and a novel 235 kb deletion (--(235)) in family B. Proband A is a coinheritance of beta(CD41-42) and alphaalphaalphaalpha(282) and showed severe beta-thalassemia intermedia phenotype. Proband B is a compound heterozygote of - (235)/alpha(CS)alpha genotype and was diagnosed with hemoglobin H disease. The clinical phenotypic features of the CNVs carriers were described, together with a complete picture of molecular structure of these rearrangements. Two CNVs are novel rearrangements in alpha-globin clusters and the alphaalphaalphaalpha(282) is the first to identify the exact insert position of a duplication region from the telomere on chromosome 16. In a conclusion, successful identification and characterization of these two novel CNVs not only demonstrates the precision and effectiveness of our strategy in analyzing the structure of unknown CNVs, but also extended the spectrum of thalassemia and provide new examples for studying genomic recombination. PMID- 27000658 TI - Ultra rapid in vivo screening for anti-Alzheimer anti-amyloid drugs. AB - More than 46 million people worldwide suffer from Alzheimer's disease. A large number of potential treatments have been proposed; among these, the inhibition of the aggregation of amyloid beta-peptide (Abeta), considered one of the main culprits in Alzheimer's disease. Limitations in monitoring the aggregation of Abeta in cells and tissues restrict the screening of anti-amyloid drugs to in vitro studies in most cases. We have developed a simple but powerful method to track Abeta aggregation in vivo in real-time, using bacteria as in vivo amyloid reservoir. We use the specific amyloid dye Thioflavin-S (Th-S) to stain bacterial inclusion bodies (IBs), in this case mainly formed of Abeta in amyloid conformation. Th-S binding to amyloids leads to an increment of fluorescence that can be monitored. The quantification of the Th-S fluorescence along the time allows tracking Abeta aggregation and the effect of potential anti-aggregating agents. PMID- 27000659 TI - Is the distal radioulnar variance useful for identification of radial head prosthesis overlengthening? A cadaver study. AB - BACKGROUND: Overlengthening by radial head prosthetic replacement leads to insufficient functionality and increased capitellar wear. It has been shown that in monopolar prostheses, the radial overlengthening by an overstuffed prosthesis leads to significant differences in the distal radioulnar variance at the wrist. This study evaluated ipsilateral ulnar variance as a predictor for overlengthening after implantation of a multipolar prosthesis. METHODS: The radial heads of seven fresh frozen upper extremities were resected and a multipolar radial head prosthesis was implanted. Thereafter, the native radioulnar variance at the wrist was documented via fluoroscopy. The alignment of the distal radioulnar joint in neutral, pronated and supinated rotational positions of the forearm was recorded fluoroscopically, and digital image analysis was performed regarding radioulnar shifting. RESULTS: Statistical analysis of the difference between native height and the manipulated states did not show consistent significant differences with stepwise overlengthening of +1.5, +3, +4.5 and +6 mm and with respect to rotational position of the forearm (p > 0.05). Interclass correlation coefficients showed excellent interobserver reliability (ICC 96%), as did tests for intraobserver reliability (ICC 98-99%). CONCLUSIONS: No consistent influence of overlengthening on the alignment of the radius and ulna at the distal radioulnar joint was found after sequential overlengthening with a multipolar prosthesis. Maybe the ligamentous structures of the forearm prevent significant longitudinal dislocation of the radius, as the multipolar prosthesis gives way by at the radiocapitellar joint. According to the data of the present study, the ipsilateral wrist is not useful in diagnosing overlengthening of the radial column in multipolar prosthetic replacement of the radial head-in contrast to the reported results with monopolar prostheses. PMID- 27000660 TI - Hydrogel coated mesh decreases tissue reaction resulting from polypropylene mesh implant: implication in hernia repair. AB - PURPOSE: Use of polypropylene mesh (PPM) in hernia repair is associated with tissue reactivity. We examined, in a rat model, a novel non-biodegradable hydrogel coated PPM which may allow for decreased inflammation and a decreased foreign body reaction. METHODS: Through a dorsal midline incision, a 2 cm * 2 cm section of PPM (either coated or uncoated) was placed on the fascial surface 1.5 cm from the incision on the dorsal wall of Sprague-Dawley rats. At 2 and 12 weeks after placement, the PPM and surrounding tissue were harvested. A board-certified dermatopathologist examined H&E stained slides for fibrosis and foreign body reaction. In addition, tissues were stained for apoptotic cells, oxidative damage, macrophages, fibroblasts, neovascularization and metalloproteases. RESULTS: At 2 and 12 weeks, there was a greater than 95 % decrease in foreign body giant cells in coated PPM samples compared to uncoated; fibrosis was decreased by 50 %. At 2 and 12 weeks, oxidative damage, fibroblast accumulation, apoptosis and macrophages were significantly decreased in coated PPM samples compared to uncoated PPM. CONCLUSION: These results demonstrate that a non biodegradable hydrogel coating of PPM led to significant reduction in foreign body reaction, oxidative stress and apoptosis compared to uncoated PPM in vivo, and suggest that this coating could be clinically useful in hernia repair. PMID- 27000661 TI - Breast cancer in a male-to-female transsexual patient with a BRCA2 mutation. AB - Breast cancer is rare in male patients. Certain predisposing factors, be they genetic (e.g., BRCA2 gene mutations) or hormonal (imbalance between estrogen and androgen levels), have been implicated in male breast cancer pathophysiology. Male-to-female (MtF) transsexualism is a condition that generally involves cross sex hormone therapy. Anti-androgens and estrogens are used to mimic the female hormonal environment and induce the cross-sex secondary characteristics. In certain situations, the change in the hormonal milieu can be disadvantageous and favor the development of hormone-dependent pathologies, such as cancer. We report a case of a MtF transgender patient who developed breast cancer after 7 years of cross-sex hormonal therapy. The patient was found to be BRCA2 positive, and suffered recurrent disease. The patient was unaware of being a member of an established BRCA2 mutation-positive kindred. This represents the first case of a BRCA2 mutation predisposing to breast cancer in a MtF transgender patient. PMID- 27000662 TI - Clonal origin and spread of metastatic prostate cancer. AB - Metastatic disease is responsible for the majority of prostate cancer deaths. The standard treatment for metastatic disease is surgical or chemical castration in the form of androgen deprivation therapy. Despite initial success and disease regression, resistance to therapy ultimately develops and the disease transitions to castration-resistant prostate cancer, which is uniformly fatal. Thus, developing an understanding of genetic evolution in metastasis and in response to therapy has been a focus of recent studies. Large-scale sequencing studies have provided an expansive catalog of the mutation events that occur in the prostate cancer genome at various stages of disease progression. Small-scale studies have interrogated the genomic composition of multiple metastatic sites within individual patients or have tracked clonal evolution longitudinally in tissues, circulating tumor cells, or circulating tumor DNA. Collectively, these efforts have provided a new conceptual framework for understanding the origin of prostate cancer, as well as the origin and evolution of metastatic disease. In this review, we highlight these recent insights into the spatiotemporal landscape of genetic evolution of prostate cancer. PMID- 27000663 TI - CT imaging vs. traditional radiographic imaging for evaluating Harris Lines in tibiae. AB - SUMMARY: This paper is the first to systematically investigate computer tomography (CT) images vs. ordinary flat plane radiography for evaluating Harris Lines (HL) on tibiae. Harris Lines are traditionally investigated using radiographic images and recorded as either present or absent, or by counting the number of HL. Seventy-four pairs of human sub-adult and adult archaeological tibiae were used in this study. Both image methods were tested for intra- and inter-observer agreement and the methods were then compared. Analysis was performed with the tibiae divided into younger (n = 19) and older sub-adults (n = 26) and adults (n = 29), as well as all tibiae combined (n = 74). This study found that the intra- and inter-observer agreement was very similar for each method, but both image methods performed less well for counting the number of HL. Direct comparison between CT images and radiographic images showed good agreement for presence or absence of HL and less agreement for counting HL. There appeared to be no systematic pattern for dividing the material according to bone length (and thereby age). Overall, this paper concludes that the performance of CT images is comparable to traditional flat plane radiography for evaluating HL on archaeological dry bone specimens of tibiae. Further, due to the lower performance of counting the number of HL, it appears advisable to only record the presence or absence of HL rather than counting the number of HL. PMID- 27000664 TI - Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma. AB - Microvesicles (MVs) secreted from cells have been found to mediate signal transduction between cells. In the tumor microenvironment, VEGF released from cancer cells plays a key role in promoting tumor angiogenesis. In this study, we characterized the inhibitory effect of MV-delivered miR-29a/c on angiogenesis and tumor growth in gastric cancer (GC). We found that the downregulation of miR 29a/c increases VEGF expression and release in GC cells, promoting the growth of vascular cells. By simulating the tumor microenvironment, the MV-delivered miR 29a/c significantly suppresses VEGF expression in GC cells, inhibiting vascular cell growth, metastasis, and tube formation. We also used a tumor implantation mouse model to show that secreted MVs containing overexpressed miR-29a/c significantly reduced the growth rate of the vasculature and tumors in vivo. To conclude, our results contribute to a novel anti-cancer strategy using miRNA containing MVs to control tumor cell growth by blocking angiogenesis. PMID- 27000665 TI - Dissolution, dislocation and dimensional changes of endodontic sealers after a solubility challenge: a micro-CT approach. AB - AIM: To evaluate, using a novel micro-CT approach, the solubility and dimensional changes of an MTA-based sealer inside the root canal system after a solubility challenge. The MTA-based material (MTA Fillapex) was compared to a gold standard epoxy-based endodontic sealer (AH Plus). METHODOLOGY: Ten human mandibular premolars with a single canal were divided randomly into two groups (n = 5) according to the sealer used. The canals were instrumented using the Reciproc System (VDW) with a R40 file and filled with R40 gutta-percha cones and one of the sealers. The filled canals were immediately scanned in a micro-CT, and after that, the teeth were immersed in 20 mL phosphate-buffered saline (PBS) at 37 degrees C for 7 days, when they were removed and rescanned. Final image stacks were registered against the initial stacks and the numerical difference between the initial and final volume of the filling material was obtained. Calculations were performed to identify dimensional changes of the filling material. All image stacks were 3D rendered to disclose areas of dislocation of the filling material inside or outside the root canal. The Shapiro-Wilk's test revealed that data were normally distributed; thus, the Student's t-test was used to detect statistically significant changes, assuming a 5% alpha-error. RESULTS: No significant changes were seen for the percentage volume of material lost after the solubility challenge for both AH Plus and MTA Fillapex groups (1.44% and 1.16%, respectively). A significant difference was, however, found for the volume of filling material which revealed dimensional changes after the solubility test (6.68% for MTA Fillapex and 1.09% for AH Plus). In fact, observation of 3D models disclosed that MTA Fillapex was associated with material extrusion through the foramen in all but one sample. In AH Plus filled samples, no material extrusion was detected. CONCLUSIONS: Although the solubility of both sealers was similar using this novel micro-CT approach, MTA Fillapex was associated with significant dimensional changes related to material extrusion through the apex after PBS storage compared to AH Plus. PMID- 27000666 TI - Coulomb-corrected molecular orbital tomography of nitrogen. AB - High-order harmonic generation (HHG) from aligned molecules has provided a promising way to probe the molecular orbital with an Angstrom resolution. This method, usually called molecular orbital tomography (MOT) replies on a simple assumption of the plane-wave approximation (PW), which has long been questioned due to that PW approximation is known to be valid in the keV energy region. However, the photon energy is usually no more than 100 eV in HHG. In this work, we experimentally reconstruct the highest occupied molecular orbital (HOMO) of nitrogen (N2) by using a Coulomb-corrected MOT (CCMOT) method. In our scheme, the molecular continuum states are described by a Coulomb wave function instead of the PW approximation. With CCMOT, the reconstructed orbital is demonstrated to agree well with the theoretical prediction and retain the main features of the HOMO of N2. Compared to the PW approximation method, the CCMOT shows a significant improvement in eliminating the artificial structures caused by PW approximation. PMID- 27000668 TI - [Comparison of Japanese Notation and Meanings among Three Terminologies in Radiological Technology Domain]. AB - PURPOSE: The purpose of this study is to investigate the differences in the notation of technical terms and their meanings among three terminologies in Japanese radiology-related societies. MATERIALS AND METHODS: The three terminologies compared in this study were "radiological technology terminology" and its supplement published by the Japan Society of Radiological Technology, "medical physics terminology" published by the Japan Society of Medical Physics, and "electric radiation terminology" published by the Japan Radiological Society. Terms were entered into spreadsheets and classified into the following three categories: Japanese notation, English notation, and meanings. In the English notation, terms were matched to character strings in the three terminologies and were extracted and compared. The Japanese notations were compared among three terminologies, and the difference between the meanings of the two terminologies radiological technology terminology and electric radiation terminology were compared. RESULTS AND DISCUSSION: There were a total of 14,982 terms in the three terminologies. In English character strings, 2,735 terms were matched to more than two terminologies, with 801 of these terms matched to all the three terminologies. Of those terms in English character strings matched to three terminologies, 752 matched to Japanese character strings. Of the terms in English character strings matched to two terminologies, 1,240 matched to Japanese character strings. With regard to the meanings category, eight terms had mismatched meanings between the two terminologies. For these terms, there were common concepts between two different meaning terms, and it was considered that the derived concepts were described based on domain. PMID- 27000667 TI - Integrating computational and chemical biology tools in the discovery of antiangiogenic small molecule ligands of FGF2 derived from endogenous inhibitors. AB - The FGFs/FGFRs system is a recognized actionable target for therapeutic approaches aimed at inhibiting tumor growth, angiogenesis, metastasis, and resistance to therapy. We previously identified a non-peptidic compound (SM27) that retains the structural and functional properties of the FGF2-binding sequence of thrombospondin-1 (TSP-1), a major endogenous inhibitor of angiogenesis. Here we identified new small molecule inhibitors of FGF2 based on the initial lead. A similarity-based screening of small molecule libraries, followed by docking calculations and experimental studies, allowed selecting 7 bi naphthalenic compounds that bound FGF2 inhibiting its binding to both heparan sulfate proteoglycans and FGFR-1. The compounds inhibit FGF2 activity in in vitro and ex vivo models of angiogenesis, with improved potency over SM27. Comparative analysis of the selected hits, complemented by NMR and biochemical analysis of 4 newly synthesized functionalized phenylamino-substituted naphthalenes, allowed identifying the minimal stereochemical requirements to improve the design of naphthalene sulfonates as FGF2 inhibitors. PMID- 27000669 TI - [Accuracy of Resolution Recovery in PSF-based Fully-3D PET Image Reconstruction: Simulation and Phantom Study in Multicenter Trial]. AB - PURPOSE: Recently, the quality of positron emission tomography (PET) images has rapidly improved using resolution recovery algorithm with point spread function (PSF). The aim of this study was to investigate the accuracy of the resolution recovery algorithm using three different PET systems. METHODS: Three PET scanner models, the GE Discovery 600 M (D600M), SIEMENS Biograph mCT (mCT), and SHIMADZU SET-3000GCT/X (3000GCT) were used in this study. The radial dependences of spatial resolution (full width at half maximum: FWHM) were obtained by point source measurements (0.9 mmphi). All PET data were acquired in three-dimensional (3D) mode and reconstructed using the filtered back projection (FBP) , 3D-ordered subsets expectation maximization (3D-OSEM or dynamic row-action maximum likelihood algorithm) , and 3D-OSEM+PSF (PSF) algorithms. Two indicators, aspect ratio (ASR) and resolution recovery ratio (RRR), were calculated from measured FWHMs and compared among the three PET scanners. RESULTS: In D600 and 3000GCT, distortions of the radial direction were slightly increased at circumference of field of view (FOV). On the other hand, random distortions were occurred in both radial and tangential direction in mCT. ASRs calculated from 3D-OSEM images at circumference of FOV were 2.06, 1.22, and 2.04 on D600M, mCT, and 3000GCT, respectively. ASR improved with PSF in all PET scanners. On the other hand, RRR with PSF were calculated 57.6%, 61.4%, and 31.6%, respectively. CONCLUSION: Our results suggest that the spatial resolutions of PET images could be improved with PSF algorithm in all PET systems; however, effect of PSF was different depending on PET systems. Furthermore, PSF algorithm could not completely improve spatial resolutions in circumference of FOV. PMID- 27000670 TI - [Usefulness of Determining Acquisition Time by True Count Rate Measurement Method for Delivery 18F-FDG PET/CT]. AB - A stable quality of delivery 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) requires suitable acquisition time, which can be obtained from an accurate true count of 18F-FDG. However, the true count is influenced by body mass index (BMI) and attenuation of 18F-FDG. In order to remove these influences, we have developed a new method (actual measurement method) to measure the actual true count rate based on sub-pubic thigh, which allows us to calculate a suitable acquisition time. In this study, we aimed to verify the acquisition count through our new method in terms of two categories: (1) the accuracy of acquisition count and (2) evaluation of clinical images using physical index. Our actual measurement method was designed to obtain suitable acquisition time through the following procedure. A true count rate of sub-pubic thigh was measured through detector of PET, and used as a standard true count rate. Finally, the obtained standard count rate was processed to acquisition time. This method was retrospectively applied to 150 patients, receiving 18F-FDG administration from 109.7 to 336.8 MBq, and whose body weight ranged from 37 to 95.4 kg. The accuracy of true count was evaluated by comparing relationships of true count, relative to BMI or to administered dose of 18F-FDG. The PET/CT images obtained by our actual measurement method were assessed using physical index. Our new method resulted in accurate true count, which was not influenced by either BMI or administered dose of 18F-FDG, as well as satisfied PET/CT images with recommended criteria of physical index in all patients. PMID- 27000671 TI - [A Quality Assurance (QA) System with a Web Camera for High-dose-rate Brachytherapy]. AB - PURPOSE: The quality assurance (QA) system that simultaneously quantifies the position and duration of an (192)Ir source (dwell position and time) was developed and the performance of this system was evaluated in high-dose-rate brachytherapy. METHODS: This QA system has two functions to verify and quantify dwell position and time by using a web camera. The web camera records 30 images per second in a range from 1,425 mm to 1,505 mm. A user verifies the source position from the web camera at real time. The source position and duration were quantified with the movie using in-house software which was applied with a template-matching technique. RESULTS: This QA system allowed verification of the absolute position in real time and quantification of dwell position and time simultaneously. It was evident from the verification of the system that the mean of step size errors was 0.31+/-0.1 mm and that of dwell time errors 0.1+/-0.0 s. Absolute position errors can be determined with an accuracy of 1.0 mm at all dwell points in three step sizes and dwell time errors with an accuracy of 0.1% in more than 10.0 s of the planned time. CONCLUSION: This system is to provide quick verification and quantification of the dwell position and time with high accuracy at various dwell positions without depending on the step size. PMID- 27000672 TI - [Investigation of an Optimum Determination Method of Exposure Index for Posterior Anterior Chest Radiographs Using an Auto Exposure Control]. AB - Fifty posterior-anterior chest radiographs taken using an auto exposure control were evaluated in order to find an optimum determination method of the exposure index (EI). Four types of the relevant image regions were tested: (a) full image, (b) central 25% area, (c) full image excluding direct x-ray area, and (d) pulmonary area only, whereas four types of the value of interest (VOI) were adopted to each relevant image region: mean, median, mode, and middle. When the target EI was determined as the average of the 50 images, the deviation index (DI) was within +/-1.0 only if pulmonary area was selected as the relevant image region, with the VOI of mean, median, and middle. This result strongly suggests that pulmonary area should be selected as the relevant image region of an EI when an auto exposure control is used. PMID- 27000673 TI - [Development of a Lead-covered Case for a Wireless X-ray Output Analyzer to Perform CT Half-value Layer Measurements]. AB - Measurement of the half-value layer (HVL) is a difficult task in computed tomography (CT) , because a nonrotating X-ray tube must be used. The purpose of this study is to develop a lead-covered case, which enables HVL measurements with a rotating CT X-ray tube. The lead-covered case was manufactured from acrylic and lead plates, which are 3 mm thick and have a slit. The slit-detector distance can be selected between 14 mm and 122 mm. HVL measurements were performed using a wireless X-ray output analyzer "Piranha." We used the following exposure conditions: tube voltages of 80, 100, and 120 kV; a tube current of 550 mA; and an exposure time of 1.0 s. The HVLs were measured by using the following two methods: (a) Nonrotating method-a conventional method that uses the nonrotating exposure mode. (b) Rotating method-a new method that uses the lead-covered case and the rotating exposure mode. As a result, when the slit-detector distance was 58 mm, the HVL values obtained by the nonrotating and rotating methods were 4.38 and 4.24 mmAl at 80 kV, 5.51 and 5.37 mmAl at 100 kV, 6.61 and 6.48 mmAl at 120 kV, respectively. A lead-covered case, which enables the measurement of the HVL in a rotating X-ray tube, was developed. The case is useful in measuring the HVLs at facilities that cannot fix the X-ray tube. PMID- 27000674 TI - [Evaluation of a Post-analysis Method for Cumulative Dose Distribution in Stereotactic Body Radiotherapy]. AB - PURPOSE: The purpose of this study was to evaluate a post-analysis method for cumulative dose distribution in stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT) . METHOD: VMAT is capable of acquiring respiratory signals derived from projection images and machine parameters based on machine logs during VMAT delivery. Dose distributions were reconstructed from the respiratory signals and machine parameters in the condition where respiratory signals were without division, divided into 4 and 10 phases. The dose distribution of each respiratory phase was calculated on the planned four dimensional CT (4DCT). Summation of the dose distributions was carried out using deformable image registration (DIR), and cumulative dose distributions were compared with those of the corresponding plans. RESULTS AND DISCUSSION: Without division, dose differences between cumulative distribution and plan were not significant. In the condition where respiratory signals were divided, dose differences were observed over dose in cranial region and under dose in caudal region of planning target volume (PTV). Differences between 4 and 10 phases were not significant. CONCLUSION: The present method was feasible for evaluating cumulative dose distribution in VMAT-SBRT using 4DCT and DIR. PMID- 27000675 TI - [The People Who Contributed to the Academic Society: Former Directors of JSRT Hokkaido "Mr. Koji Hagiwara" and "Mr. Takayuki Shibata"]. PMID- 27000676 TI - [Elementary Knowledge of Wireless LAN Equipment]. PMID- 27000677 TI - [Inspection of Hepatocellular Carcinoma 1: Ultrasonography]. PMID- 27000678 TI - [Report of ECR 2015]. PMID- 27000679 TI - [Introduction of "DataBook2015; Medical Imaging and Radiological Systems Industries by charts and data"]. PMID- 27000680 TI - [For the Future of the Japanese Society of Radiological Technology]. PMID- 27000681 TI - The Case Against the Case for Procreative Beneficence (PB). AB - Julian Savulescu's principle of procreative beneficence (PB) states that, other things being equal, and of the possible children they could have, a couple contemplating procreation are morally obliged to (attempt to) procreate the child with the best chance of the best life. The critique of PB is in three parts. The first part argues that PB rests on a particular conception of the good life, and that alternative conceptions of the good life afford no obvious way in which PB can be rendered operational. The second part identifies six flaws in the attempt to justify PB in terms of a particular conception of the good life according to which the best life is understood as the life with the most well-being. The third part explores some of the uncertainties that surround the potential implications and ramifications of adopting the principle. The overall purpose is not to demonstrate that the principle is untenable, but only to demonstrate that no compelling reason has yet been given for adhering to it. PMID- 27000682 TI - Intraoperative salvage does not affect expression of markers for erythrophagocytosis. PMID- 27000683 TI - Autoimmune hepatitis: a manifestation of immune reconstitution inflammatory syndrome in HIV infected patients? AB - OBJECTIVE: To describe a case series of patients presenting with autoimmune hepatitis after initiation of antiretroviral therapy. MATERIALS AND METHODS: The demographics, clinical and laboratory features, and therapeutic response of HIV infected patients on antiretroviral therapy presenting to our Division between November 2011 and November 2014 with elevated liver enzymes, were analysed. RESULTS: Nine patients with elevated liver enzymes, immunoglobulin G and autoimmune markers in keeping with autoimmune hepatitis were identified. All were anti-hepatitis C virus negative. One patient was hepatitis B surface antigen positive but his hepatitis B viral load was undetectable. All patients denied using any traditional herbal remedies. Liver histology was consistent with autoimmune hepatitis showing interface hepatitis and infiltrates of lymphocytes and plasma cells. Diagnosis was made according to the Autoimmune Hepatitis Group Scoring Systems. All patients were started on 15-20 mg of oral prednisone with clinical and biochemical improvement after 1-6 weeks. CONCLUSIONS: Immune reconstitution related autoimmune hepatitis should be considered in the differential diagnosis of hepatitis in the HIV-infected patient on antiretroviral therapy. Liver biopsy should be performed and the diagnosis confirmed using scoring systems developed by the Autoimmune Hepatitis Group. Timely treatment with prednisone and other agents for autoimmune hepatitis is indicated, and can be lifesaving in acute liver failure. PMID- 27000684 TI - Acute exercise restores insulin clearance in diet-induced obese mice. AB - The aim of this study was to investigate the insulin clearance in diet-induced obese (DIO) mice submitted to acute endurance exercise (3h of treadmill exercise at 60-70% VO2max). Glucose-stimulated insulin secretion in isolated islets; ipGTT; ipITT; ipPTT; in vivo insulin clearance; protein expression in liver, skeletal muscle, and adipose tissue (insulin degrading enzyme (IDE), insulin receptor subunitbeta(IRbeta), phospho-Akt (p-Akt) and phospho-AMPK (p-AMPK)), and the activity of IDE in the liver and skeletal muscle were accessed. In DIO mice, acute exercise reduced fasting glycemia and insulinemia, improved glucose and insulin tolerance, reduced hepatic glucose production, and increased p-Akt protein levels in liver and skeletal muscle and p-AMPK protein levels in skeletal muscle. In addition, insulin secretion was reduced, whereas insulin clearance and the expression of IDE and IRbeta were increased in liver and skeletal muscle. Finally, IDE activity was increased only in skeletal muscle. In conclusion, we propose that the increased insulin clearance and IDE expression and activity, primarily, in skeletal muscle, constitute an additional mechanism, whereby physical exercise reduces insulinemia in DIO mice. PMID- 27000685 TI - Testosterone deprivation accelerates cardiac dysfunction in obese male rats. AB - Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats. PMID- 27000686 TI - Physical activity and health of adults with cystic fibrosis. PMID- 27000687 TI - New targeted therapies in the treatment of pulmonary arterial hypertension: getting to the heart of the problem. PMID- 27000688 TI - Analyses of abdominal fat and sleep apnea. PMID- 27000689 TI - Erratum. PMID- 27000690 TI - Editorial. PMID- 27000691 TI - Bion and C.G. Jung. How did the container-contained model find its thinker? The fate of a cryptomnesia. AB - This paper investigates the possible impact of C.G. Jung's Tavistock Lectures on Bion's concept of the living container. In the first part of the paper, the author offers clues pointing to such an essential impact, which can be found in text passages as well as in the facts of the Bion-Beckett case, up to and including Bion's first publication of 'The imaginary twin'. The author suggests that cryptomnesia is the result of repression targeting a highly cathected author's communication which functions like a deep interpretation for the recipient, whose new theory then is a return of the repressed content as well as a transformation of it. The second part of the paper investigates the fate of the assumed cryptomnesia. From this point of view Bion's concept of the container in itself appears to be the result of growth in the container-contained mode. Finally the author deals with the question whether cryptomnesia in psychoanalytical literature can frequently be seen as the result of psychic growth. PMID- 27000692 TI - The challenges of editorship: a reflection on editing the Jung-Neumann correspondence. AB - The complete correspondence between C.G. Jung and Erich Neumann was published in 2015. This article attempts to provide insight into the practical task, as well as the theoretical background, of the editing process. The advantages and possibilities of an unabridged edition with an extensive historical contextualization are demonstrated, and compared to the approach of the editors of the Jung Letters and their selection therein of Jung's letters to Neumann. The practical points under consideration include the establishment of the letter corpus, the ascertainment of dates and the chronological arrangement of the letter exchange, as well as the deciphering of handwritten letters. Theoretical aspects under discussion involve the question of the merits of a critical contextualisation and the position of the editor vis-a-vis the research object. The example of the selecting and editing of Jung's letters to Neumann by Aniela Jaffe and Gerhard Adler reveals how drastically the close ties of those editors with Jung, Neumann, and members of the Zurich analytical circles compromised their editorial work at times. The advantage for an editor being able to work from an historical distance is appreciated. PMID- 27000693 TI - Standing in the gap: ref lections on translating the Jung-Neumann correspondence. AB - This paper considers the experience of translating the correspondence between C.G. Jung and Erich Neumann as part of the Philemon series. The translator explores the similarities between analytical work and the task of translation by means of the concepts of the dialectical third and the interactional field. The history and politics of the translation of analytic writing and their consequences for the lingua franca of analysis are discussed. Key themes within the correspondence are outlined, including Jung and Neumann's pre-war exploration of Judaism and the unconscious, the post-war difficulties around the publication of Neumann's Depth Psychology and a New Ethic set against the early years of the C.G. Jung Institute in Zurich, and the development of the correspondents' relationship over time. PMID- 27000694 TI - The five functions of psychological type. AB - From the mid-1930s to the end of his life, Jung complained that most readers misunderstood the main point of his book Psychological Types. He viewed being a type as one-sided and problematic for a variety of reasons. His symbol-based solution to the 'type problem' involved developing a transcendent function to become the new dominant function of consciousness. However, this function has not featured in the popular use of his typology and Isabel Briggs Myers believed that the one-sidedness of Jung's eight types could be balanced by the auxiliary function. This has led to the transcendent function being widely ignored, and to a developmental philosophy that encourages a degree of one-sidedness. This divergence of popular type theory and analytical psychology is the result of various factors, such as Jung describing typology as containing four functions, and a letter in 1950 where Jung apparently supported Myers' version of type theory. This hinders the application of analytical psychology to normal psychology, and particularly individual and cultural development. If we refer to Jung's typology as containing five functions not four, this more accurately represents both the content of the book Psychological Types and the primary value Jung saw in typology. PMID- 27000695 TI - The Fibonacci Life-Chart Method (FLCM) as a foundation for Carl Jung's theory of synchronicity. AB - Since the scientific method requires events to be subject to controlled examination it would seem that synchronicities are not scientifically investigable. Jung speculated that because these incredible events are like the random sparks of a firefly they cannot be pinned down. However, doubting Jung's doubts, the author provides a possible method of elucidating these seemingly random and elusive events. The author draws on a new method, designated the Fibonacci Life-Chart Method (FLCM), which categorizes phase transitions and Phi fractal scaling in human development based on the occurrence of Fibonacci numbers in biological cell division and self-organizing systems. The FLCM offers an orientation towards psychological experience that may have relevance to Jung's theory of synchronicity in which connections are deemed to be intrinsically meaningful rather than demonstrable consequences of cause and effect. In such a model synchronistic events can be seen to be, as the self-organizing system enlarges, manifestations of self-organized critical moments and Phi fractal scaling. Recommendations for future studies include testing the results of the FLCM using case reports of synchronistic and spiritual experiences. PMID- 27000696 TI - The psychologist who is not a psychologist: a deconstructive reading of Wolfgang Giegerich's idea of psychology proper. AB - This paper represents an archetypal and deconstructive reading of the work of Wolfgang Giegerich. In an attempt to extend and philosophically develop Jung's late-life view of the objective psyche, Giegerich, via Hegel, defines psychology proper as fundamentally separate from the everyday person and the 'human, all-too human' aspects of the soul. It is argued that, in so doing, Giegerich removes the human person from being the primary focus of his psychology and creates instead a hierarchy of ideas and values privileging syntax over semantics, the logical over the empirical, and thinking over imagination. This bypasses the emotionality of the everyday person/patient and also renders psychology proper unable to address the day-to-day practice of the analyst. Giegerich attempts to rectify this problem by re-incorporating what he had previously rejected, making his theory more complex than is apparent in his binary oppositions. In the end, however, it remains a question to what extent Giegerich is successful in avoiding a binary scission (Saban 2015) or a tendency to regularly de-emphasize the human aspect of the soul (Hoedl 2015) in his need to continue to heroically push off from the ego seeking total freedom from neurosis and from our humanity. PMID- 27000697 TI - Snow White took a bite of the poisoned apple... but what about today? PMID- 27000701 TI - Genetic characterization of OVC8 lytic phage for Vibrio cholerae O1. AB - BACKGROUND: Epidemics and pandemics of cholera, a diarrheal disease, are attributed to Vibrio cholera serogroups O1 and O139. In recent years, specific lytic phages of V. cholera have been proposed to be important factors in the cyclic occurrence of cholera in endemic areas. However, the role and potential participation of lytic phages during long interepidemic periods of cholera in non endemic regions have not yet been described. The purpose of this study was to isolate and characterize specific lytic phages of V. cholera O1 strains. METHODS: Sixteen phages were isolated from wastewater samples collected at the Endho Dam in Hidalgo State, Mexico, concentrated with PEG/NaCl, and purified by density gradient. The lytic activity of the purified phages was tested using different V. cholerae O1 and O139 strains. Phage morphology was visualized by transmission electron microscopy (TEM), and phage genome sequencing was performed using the Genome Analyzer IIx System. Genome assembly and bioinformatics analysis were performed using a set of high-throughput programs. Phage structural proteins were analyzed by mass spectrometry. RESULTS: Sixteen phages with lytic and lysogenic activity were isolated; only phage OVC8 showed specific lytic activity against V. cholerae O1 strains. TEM images of OVC8 revealed a phage with a short tail and an isometric head. The OVC8 genome comprises linear double-stranded DNA of 39,422 bp with 50.8 % G + C. Of the 48 annotated ORFs, 16 exhibit homology with sequences of known function and several conserved domains. Bioinformatics analysis showed multiple conserved domains, including an Ig domain, suggesting that OVC8 might adhere to different mucus substrates such as the human intestinal epithelium. The results suggest that OVC8 genome utilize the "single-stranded cohesive ends" packaging strategy of the lambda-like group. The two structural proteins sequenced and analyzed are proteins of known function. CONCLUSIONS: OVC8 is a lytic phage with specific activity against V. cholerae O1 strains and is grouped as a member of the VP2-like phage subfamily. The encoding of an Ig domain by OVC8 makes this phage a good candidate for use in phage therapy and an alternative tool for monitoring V. cholerae populations. PMID- 27000702 TI - Increased resistin levels in the serum and cerebrospinal fluid of patients with neuromyelitis optica. AB - INTRODUCTION: Resistin, which acts as a pro-inflammatory cytokine, has been implicated in the pathogenesis of several autoimmune diseases. However, the involvement of resistin in neuromyelitis optica (NMO), a severe inflammatory central nervous system disorder that targets the optic nerve and spinal cord, remains unclear. METHODS: We measured serum and cerebrospinal fluid (CSF) resistin levels in patients with NMO and controls matched by age and sex. The link between resistin levels and clinical variables in NMO was subsequently assessed. RESULTS: The concentrations of serum and CSF resistin were significantly higher in patients with NMO than in controls, and decreased following treatment with methylprednisolone. High sensitivity C-reactive protein (hs-CRP) levels and annualized relapse rate positively correlated with resistin levels in patients with NMO. CONCLUSION: Resistin might be a useful biomarker of inflammation in NMO, and a potential target for the treatment of NMO. PMID- 27000703 TI - High-risk drinking is associated with dyslipidemia in a different way, based on the 2010-2012 KNHANES. AB - BACKGROUND: The Alcohol Use Disorders Identification Test (AUDIT) questionnaire is a simple and useful method for the early detection of hazardous and harmful drinking. In this study, we examined the association between alcohol drinking pattern and dyslipidemia in Korean adults. METHODS: This cross-sectional study included 14,308 participants who took part in the 2010-2012 Korean National Health and Nutrition Examination Survey. We categorized alcohol drinking patterns into three groups. We classified dyslipidemia into hypercholesterolemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hyper-LDL-cholesterolemia, and hyper-non-HDL-cholesterolemia. RESULTS: Of those who participated, 25.1% of men and 4.8% of women were high-risk drinkers. Compared with the low-risk group, Odd Ratios for hypercholesterolemia and hypertriglyceridemia in the high-risk group were 1.198 (1.001-1.434) and 1.979 (1.622-2.413) for men. Odd Ratios for hypo-HDL cholesterolemia in the high-risk group was 0.351 (0.279-0.441) in men and 0.413 (0.291-0.586) in women. Compared with the low-risk participants, the high-risk group was associated with higher prevalence and increased risk for hyper-LDL cholesterolemia in both sexes (1.541 [1.467-1.913] for men and 1.631 [1.034 2.575] for women). CONCLUSIONS: High-risk drinking was associated with higher risk for hypertriglyceridemia and hyper-LDL-cholesterolemia in both sexes and hypercholesterolemia in men but lower risk for hypo-HDL-cholesterolemia in both sexes. PMID- 27000704 TI - Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/beta-arrestin2/TGF-beta activated kinase-1 binding protein-1 signaling pathway. AB - Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor beta activated kinase 1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/beta-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti inflammatory effects via beta-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH. PMID- 27000705 TI - Development across the life cycle. PMID- 27000706 TI - Risk factors of suicide attempts by poisoning: review. AB - INTRODUCTION: Suicide, a complex and universal human phenomenon, is a major public health problem. This study reviewed the literature about the major risk factors associated with suicide attempts by poisoning. METHODS: An integrative review of the literature was performed in databases (LILACS, PubMed and MEDLINE) to search for studies published between 2003 and 2013, using the following keywords: suicide, attempted; poisoning; risk factors. Inclusion criteria were: original study with abstract, sample of adults, and attempted suicide by poisoning in at least 50% of the study population. RESULTS: Two hundred and nineteen studies were retrieved and read by two independent examiners, and 22 were included in the study. The main risk factors for suicide attempts by poisoning were female sex, age 15-40 years, single status, little education, unemployment, drug or alcohol abuse or addiction, psychiatric disorder and psychiatric treatment using antidepressants. CONCLUSION: Further prospective studies should be conducted to confirm these risk factors or identify others, and their findings should contribute to planning measures to prevent suicide attempts. PMID- 27000707 TI - How semantic deficits in schizotypy help understand language and thought disorders in schizophrenia: a systematic and integrative review. AB - INTRODUCTION: Disorders of thought are psychopathological phenomena commonly present in schizophrenia and seem to result from deficits of semantic processing. Schizotypal personality traits consist of tendencies to think and behave that are qualitatively similar to schizophrenia, with greater vulnerability to such disorder. This study reviewed the literature about semantic processing deficits in samples of individuals with schizotypal traits and discussed the impact of current knowledge upon the comprehension of schizophrenic thought disorders. Studies about the cognitive performance of healthy individuals with schizotypal traits help understand the semantic deficits underlying psychotic thought disorders with the advantage of avoiding confounding factors usually found in samples of individuals with schizophrenia, such as the use of antipsychotics and hospitalizations. METHODS: A search for articles published in Portuguese or English within the last 10 years on the databases MEDLINE, Web of Science, PsycInfo, LILACS and Biological Abstracts was conducted, using the keywords semantic processing, schizotypy and schizotypal personality disorder. RESULTS: The search retrieved 44 manuscripts, out of which 11 were firstly chosen. Seven manuscripts were additionally included after reading these papers. CONCLUSION: The great majority of the included studies showed that schizotypal subjects might exhibit semantic processing deficits. They help clarify about the interfaces between cognitive, neurophysiological and neurochemical mechanisms underlying not only thought disorders, but also healthy human mind's creativity. PMID- 27000708 TI - The Peer Aggressive and Reactive Behaviors Questionnaire (PARB-Q): evidence of validity in the Brazilian context. AB - OBJECTIVE: To evaluate the psychometric properties of the Brazilian version of the Peer Aggressive and Reactive Behaviors Questionnaire (PARB-Q), a self-report instrument comprising two independent scales that assess aggressive behavior and reactions to peer aggression. METHOD: A total of 727 elementary schoolchildren aged 8-13 years (52% boys) were included. Exploratory and confirmatory factor analyses were used to evaluate the factor structure. RESULTS: The Brazilian version of the PARB-Q was consistent with the original version. The results of the exploratory factor analyses (EFA) indicated a one-factor solution for the first scale (Peer Aggression Scale) and a three-factor solution (Reactive Aggression, Seeking Teacher Support, and Internalizing Reaction) for the Reaction to Peer Aggression Scale. The confirmatory analyses for both scales yielded good fit indices. CONCLUSION: The results of the statistical analyses suggested adequate psychometric properties and satisfactory validity and reliability of the Brazilian version of the PARB-Q, making it a useful tool for assessing aggressive behavior as well as children's reactions to aggression by their peers. PMID- 27000709 TI - Patterns of non-medical use of methylphenidate among 5th and 6th year students in a medical school in southern Brazil. AB - OBJECTIVES: To evaluate the prevalence of methylphenidate (MPH) use among 5th and 6th year medical students, to discriminate MPH use with and without medical indication, and to correlate MPH use with alcohol intake. METHODS: This is a cross-sectional study in which medical students were invited to answer a questionnaire to evaluate academic and socioeconomic status, MPH use patterns, and attitudes towards neuroenhancing drugs. The Alcohol Use Disorders Identification Test (AUDIT) was used to assess alcohol intake; a score >= 8 suggests potentially hazardous alcohol use. RESULTS: Fifty-two participants (34.2%) had already used MPH, of which 35 (23.02%) had used it without medical indication. The number of 6th year students who had used MPH was more than twice higher than that of their 5th year counterparts (32.89 vs. 13.15%, respectively; p = 0.004). Also, 43.6% (p = 0.031) of the users of MPH had an AUDIT score >= 8; 33.3% (p = 0.029) of non-medical users of MPH had an AUDIT score >= 8. CONCLUSIONS: In this study, the use of MPH without medical indication was prevalent. Our findings also confirmed the association between non-medical use of MPH and potentially hazardous alcohol use. PMID- 27000710 TI - Translation and adaptation of the Child Posttraumatic Cognitions Inventory (cPTCI) to Brazilian Portuguese. AB - INTRODUCTION: Experiencing a traumatic event is a risk factor for the development of mental illness, especially posttraumatic stress disorder. A child's appraisals of a traumatic event may play a prominent role in the development or maintenance of the disorder. Therefore, subjective responses should be evaluated to understand the impact of a traumatic event on a child's life. This study translated and adapted the Child Posttraumatic Cognitions Inventory (cPTCI) for use in linguistic and cultural contexts in Brazil. METHODS: The process included translation, back-translation, language expert evaluation and expert committee's evaluation. RESULTS: Content validity index scores were good for all dimensions after evaluation by two judges and one reformulation. The back-translation of the final version also showed that the cPTCI items in Brazilian Portuguese maintained the same meanings of the original in English. This version was tested in a sample of the target population, and all the items were above the cut-off point (minimum = 3.6; maximum = 4.0). CONCLUSIONS: This study was successful in producing a Brazilian version of the cPTCI. Further studies are underway to examine the reliability and the factorial and concurrent validity of cPTCI subscales. PMID- 27000711 TI - Panic disorder and psychoactive substance use in primary care. AB - OBJECTIVE: To identify the association between panic disorder and licit and illicit substance use in the population provided with primary care in the southern Brazil. METHODS: This is a cross-sectional study with patients from three primary care centers. We used the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to evaluate substance use and the Mini International Neuropsychiatric Interview (MINI) to diagnose panic disorder. RESULTS: A total of 1,081 subjects were evaluated. The prevalence of panic disorder was 5.6%. Panic disorder was associated with using marijuana (p = 0.001), tobacco (p = 0.001), cocaine (p < 0.001), and other illicit substances (p < 0.001). CONCLUSION: A significant association is noticed between panic disorder and licit and illicit substance use, thus, it is interesting to rethink the approach to treatment/intervention in patients with dual diagnosis. PMID- 27000712 TI - Mothers who were sexually abused during childhood are more likely to have a child victim of sexual violence. AB - INTRODUCTION: Recurrent exposure to childhood sexual abuse (CSA) seems to be higher among victims of sexual abuse. In this sense, experiences related to sexual violence can perpetuate within the family context itself in various ways. Here, we investigate the association between being exposed to CSA and having a child victim of sexual abuse. METHOD: We used a sample with 123 mothers, who were divided into 2 groups: one consisting of 41 mothers of sexually abused children and another consisting of 82 mothers of non-sexually abused children. History of exposure to CSA was evaluated by means of the Childhood Trauma Questionnaire - Short Form (CTQ) and we used a logistic regression model to estimate the prediction values regarding having or not a child exposed to sexual violence. RESULTS: Mothers of sexually abused children had significantly higher scores on CTQ, especially on the sexual abuse subscale (SA). According to our logistic regression model, higher scores on the CTQ significantly predicted the status of being a mother of children exposed to sexual violence in our sample (Wald = 7.074; p = 0.008; Exp(B) = 1.681). Years of formal education reduced the likelihood of having a child victim of sexual violence (Wald = 18.994; p = 0.001; Exp(B) = 0.497). CONCLUSION: Our findings highlight the importance of a possible intergenerational effect of sexual abuse. Family intervention and prevention against childhood maltreatment should take this issue in account. PMID- 27000714 TI - Two new polyhydroxysterols produced by Fusarium solani, an endophytic fungus from Chloranthus multistachys. AB - A highly antagonistic endophytic fungus, designated strain CL39, was originated from the leaves of Chloranthus multistachys collected in Wulong of Chongqing municipality of China in November 2015. The strain was identified as Fusarium solani based on morphological characteristics, 5.8S gene and internal transcribed spacer sequence analysis. Two new compounds, 2beta, 9alpha-dihydroxy-5alpha methoxyergosta-7, 22-diene (1), 2beta, 6beta-dihydroxy-5alpha-methoxyergosta-7, 22-diene (2) have been isolated from the culture broth of the strain. Structures of the new compounds were elucidated by detailed analysis of their spectroscopic data aided by the comparison with reported data of related derivatives, and found to belong to the polyhydroxylated steroids with a hydroxyl at C-2 instead of C-3, a rare structure among the steroids. The extract of this strain and all isolated compounds were evaluated for their antagonistic activities. PMID- 27000715 TI - Effects of spatial heterogeneity in moisture content on the horizontal spread of peat fires. AB - The gravimetric moisture content of peat is the main factor limiting the ignition and spread propagation of smouldering fires. Our aim is to use controlled laboratory experiments to better understand how the spread of smouldering fires is influenced in natural landscape conditions where the moisture content of the top peat layer is not homogeneous. In this paper, we study for the first time the spread of peat fires across a spatial matrix of two moisture contents (dry/wet) in the laboratory. The experiments were undertaken using an open-top insulated box (22*18*6cm) filled with milled peat. The peat was ignited at one side of the box initiating smouldering and horizontal spread. Measurements of the peak temperature inside the peat, fire duration and longwave thermal radiation from the burning samples revealed important local changes of the smouldering behaviour in response to sharp gradients in moisture content. Both, peak temperatures and radiation in wetter peat (after the moisture gradient) were sensitive to the drier moisture condition (preceding the moisture gradient). Drier peat conditions before the moisture gradient led to higher temperatures and higher radiation flux from the fire during the first 6cm of horizontal spread into a wet peat patch. The total spread distance into a wet peat patch was affected by the moisture content gradient. We predicted that in most peat moisture gradients of relevance to natural ecosystems the fire self-extinguishes within the first 10cm of horizontal spread into a wet peat patch. Spread distances of more than 10cm are limited to wet peat patches below 160% moisture content (mass of water per mass of dry peat). We found that spatial gradients of moisture content have important local effects on the horizontal spread and should be considered in field and modelling studies. PMID- 27000716 TI - Transanal endoscopic microsurgery for large benign rectal tumors; where are the limits? AB - INTRODUCTION: Local excision is the treatment of choice for large benign rectal lesions. Transanal endoscopic microsurgery is recommended. The excision of large lesions >4 cm has been previously described. We report our series of lesions >5 cm that have been excised via the transanal endoscopic microsurgery. METHODS: Patients who underwent transanal endoscopic microsurgery for rectal tumors, between the years 2002-2012, were identified. Patients with tumors greater than 5 cm consisted the study group. Tumor diameter was determined based on fresh specimen measurements. Data pertaining to patients and tumor characteristics, operative and histopathology findings, postoperative outcomes were collected. Local recurrence and effects on anal sphincter function were assessed. RESULTS: Twenty five patients (14 female) with mean age of 70.3 +/- 10.1 years, met the inclusion criteria. The mean tumor size was 5.7 +/- 0.9 cm. The median distance from anal verge was 8 cm (range 1-17). Preoperative biopsy of the rectal tumor revealed adenoma with/without dysplasia in 24 patients. Postoperative findings were adenoma with/without dysplasia in 20 patients, T1 rectal cancer in 4 patients and tail gut cyst in one patient. Free margins were documented in 17 patients, in 7 it was involved and in one patient it could not be determined. In 2 cases the procedure was discontinued. Except for nonspecific transient fever no postoperative complications were reported. After a median follow up of 24.2 months, the 3-year LR rate was 10.9%. CONCLUSION: TEM is feasible for the treatment of large benign rectal tumors. It may be an alternative method for proctectomy in selected patients with large rectal lesions. PMID- 27000717 TI - A retrospective cohort study of pancreatic neuroendocrine tumors at single institution over 15 years: New proposal for low- and high-grade groups, validation of a nomogram for prognosis, and novel follow-up strategy for liver metastases. AB - PURPOSE: Pancreatic neuroendocrine tumors (PNETs) exhibit various tumor behaviors and symptoms that are difficult for physicians to stage and predict prognosis. We assess prognostic factors combined with staging classifications to optimal the models and try to improve follow-up strategy to monitor liver metastases after surgery. METHODS: Patients with PNETs treated at Sun Yat-sen Memorial Hospital between 2000 and 2015 were recruited. Patients were regrouped on the basis of functional status and mitotic rates. Nomograms to predict the prognostic values of classifications (AJCC, ENETS, and WHO) were constructed; the accuracy of the nomograms were quantified by the C-index and calibration plots. RESULTS: We identified 78 PNETs patients with pathological reports. Correlations with OS in univariate analysis included nonfunctional status (P = 0.002), CgA>200 ng/ml (P < 0.001), Ki-67 (3-20%, P = 0.014; >20%, P < 0.001), and mitotic rate (3-20/10HPF, P = 0.011; >20/10HPF, P < 0.001). By multivariate analysis, nonfunctional status and mitotic rate maintained significance (P = 0.039; 3-20/10HPF, P = 0.015; >20/10HPF, P = 0.007). Evaluating the new proposed system, the difference in OS between low- and high-groups was statistically significant (P = 0.001). The C index of the regrouped nomograms were higher than that of premise ones (AJCC cohort, 0.605 v 0.576, P < 0.01; ENETS cohort, 0.73 v 0.691, P < 0.01; WHO cohort, 0.678 v 0.603, P < 0.01). CONCLUSION: An prognostic model based on mitotic rates and functional status correlates strongly with survival. PNETs should return visits every 2 months for the first half years, and every 3 months as followed until 2 years after surgery. PMID- 27000718 TI - Risk factors for lymph node metastasis in ovarian cancer: Implications for systematic lymphadenectomy. AB - BACKGROUND: The purpose of this study was to assess the risk factors associated with lymph node metastases and to evaluate the role of systematic lymphadenectomy in ovarian cancer. METHODS: We retrospectively reviewed patients diagnosed with ovarian cancer between December 2004 and March 2012. Demographics, pathologic findings, and correlations with lymph node metastases were assessed. RESULTS: A total of 256 patients were identified. The mean number of removed lymph nodes was 20.5 (range, 2-57), and 84 patients (32.8%) had nodal metastases. The mean number of positive lymph nodes was 3 (range, 1-40) in patients with lymph node metastases. Univariate analysis showed that serous histology, histological grade 2-3, and CA-125 level at diagnosis >740 U/mL were significant risk factors for lymph node metastases. Multivariate analysis showed that serous histology (odds ratio [OR], 2.728; 95% confidence interval [CI], 1.072-6.945; p = 0.035), histological grade 2-3 (OR 1.897; 95% CI, 1.209-2.977; p = 0.005), and CA-125 level at diagnosis >740 U/mL (OR, 3.858; 95% CI 2.143-6.947; p < 0.001) remain the most important risk factors for lymph node metastases. The nodal metastasis rates for 0 to 1 risk factors were significantly lower than those of 2-3 risk factors (3.7% vs. 40.6%; p < 0.001). CONCLUSIONS: The current study suggests that the decision making of systematic lymphadenectomy in ovarian cancer patients should be referred to the histological type, grade, and CA-125 level at diagnosis. PMID- 27000719 TI - Laparoscopic management after failed endoscopic stone removal in nondilated common bile duct. AB - INTRODUCTION: When common bile duct (CBD) stone removal by endoscopic procedure fails, CBD exploration is an alternative procedure. However, nondilated CBD is a contraindication to choledochotomy. The purpose of this study was to investigate the results of laparoscopic CBD exploration (LCBDE) following unsuccessful endoscopic stone removal in nondilated CBD. METHODS: From January 2011 to June 2015, we retrospectively analyzed 165 LCBDEs. Group 1 was defined as patients with nondilated CBD who underwent LCBDE after failed endoscopic stone removal. Group 2 included patients with dilated CBD who received LCBDE. Outcomes of LCBDE were compared between the two groups. RESULTS: There were 23 patients in Group 1 and 142 in Group 2. No significant differences were observed in demographics other than CBD diameter. There was no significant difference in operating time, postoperative hospital stay, open conversion rate, overall postoperative complication rate, retained stone rate, and recurrence rate between the two groups. CONCLUSION: LCBDE in experienced hands is a safe and feasible option after failure of endoscopic stone removal in nondilated CBD. However, larger numbers of cases and longer follow-up are required to validate LCBDE in nondilated CBD. PMID- 27000721 TI - Molecular identification of livestock breeds: a tool for modern conservation biology. AB - Global livestock genetic diversity includes all of the species, breeds and strains of domestic animals, and their variations. Although a recent census indicated that there were 40 species and over 8000 breeds of domestic animals; for the purpose of conservation biology the diversity between and within breeds rather than species is regarded to be of crucial importance. This domestic animal genetic diversity has developed through three main evolutionary events, from speciation (about 3 million years ago) through domestication (about 12000 years ago) to specialised breeding (starting about 200 years ago). These events and their impacts on global animal genetic resources have been well documented in the literature. The key importance of global domestic animal resources in terms of economic, scientific and cultural heritage has also been addressed. In spite of their importance, there is a growing number of reports on the alarming erosion of domestic animal genetic resources. This erosion of is happening in spite of several global conservation initiatives designed to mitigate it. Herein we discuss these conservation interventions and highlight their strengths and weaknesses. However, pivotal to the success of these conservation initiatives is the reliability of the genetic assignment of individual members to a target breed. Finally, we discuss the prospect of using improved breed identification methodologies to develop a reliable breed-specific molecular identification tool that is easily applicable to populations of livestock breeds in various ecosystems. These identification tools, when developed, will not only facilitate the regular monitoring of threatened or endangered breed populations, but also enhance the development of more efficient and sustainable livestock production systems. PMID- 27000720 TI - Laparoendoscopic single-site surgery (LESS) for major urological procedures in the pediatric population: A systematic review. AB - BACKGROUND: Improvements in laparoscopic surgery have led to the introduction of laparoendoscopic single-site surgery (LESS) as an alternative to conventional laparoscopy conferring a number of possible advantages. In this review, we aim to elucidate the aspects of LESS for major urological procedures in the pediatric population. MATERIALS AND METHODS: An in-depth search of the literature was performed in the databases of PubMed and Scopus, for studies investigating the technical aspects and clinical outcomes of partial nephrectomies, nephrectomies, nephroureterectomies, varicocelectomies and pyeloplasties in children. Data on parameters such as operation time, instrumentation, perioperative complications, hospital stay and follow up period were collected and further analyzed cumulatively. RESULTS: Twenty nine studies met the inclusion criteria incorporating 386 patients who underwent 401 procedures. There were no major intraoperative complications, with only 19 patients (4.73%) facing postoperative complications. No perioperative deaths were reported. CONCLUSIONS: In the hands of experienced surgeons LESS seems a feasible, efficient and less invasive alternative to standard laparoscopy in the field of pediatric urology. There is an eminent need of well-designed randomized controlled trials comparing the two techniques. PMID- 27000722 TI - The Double Homunculus model of self-reflective systems. AB - Vladimir Lefebvre introduced the principles of self-reflective systems and proposed the model to describe consciousness based on these principles (Lefebvre V.A., 1992, J. Math. Psychol. 36, 100-128). The main feature of the model is an assumption of "the image of the self in the image of the self", that is, "a Double Homunculus". In this study, we further formalize the Lefebvre's formulation by using difference equations for the description of self-reflection. In addition, we also implement a dialogue model between the two homunculus agents. The dialogue models show the necessity of both exchange of information and observation of object. We conclude that the Double Homunculus model represents the most adequate description of conscious systems and has a significant potential for describing interactions of reflective agents in the social environment and their ability to perceive the outside world. PMID- 27000723 TI - Rapid Access to 2,2'-Bithiazole-Based Copolymers via Sequential Palladium Catalyzed C-H/C-X and C-H/C-H Coupling Reactions. AB - A rapid access to 2,2'-bithiazole-based copolymers has been developed on the basis of the sequential palladium-catalyzed C?H/C?X and C?H/C?H coupling reactions. To assemble a "copolymer" through homopolymerization, a type of symmetric A-B-A-type building block is designed as the monomer and prepared via the regioselective C5?H arylation of thiazole. A PdCl2 /CuCl-cocatalyzed oxidative C?H/C?H homopolymerization has been established to afford the 2,2' bithiazole-based copolymers with high Mn (up to 69400). The current protocol features atom- and step-economy and exhibits a potential in the highly efficient construction of conjugated copolymers. PMID- 27000724 TI - Silver-Catalyzed 7-exo-dig Cyclization of Silylenolether-ynesulfonamides. AB - Cyclization of silylenolether-ynesulfonamides proceeds at ambient temperature under mild reaction conditions under silver catalysis. Bridged compounds were obtained exclusively through 7-exo-dig reactions. The protocol is applicable to a wide range of substrates, thus leading to azabicyclic frameworks. PMID- 27000726 TI - Introduction: Why alternative donor transplantation and what are the different options and current challenges? PMID- 27000725 TI - Flexible, High Temperature, Planar Lighting with Large Scale Printable Nanocarbon Paper. AB - Highly efficient broadband thermal radiation from reduced graphene oxide (RGO) paper mixed with single-walled carbon nanotubes (CNTs) is reported. These RGO-CNT paper ribbons routinely reach 3000 K before failure, with some samples exceeding 3300 K, higher than any other carbon nanomaterial. Excellent performance is achieved, with ~90% radiation efficiency, 200 000 on/off cycles, and stable operation for more than 50 hours. PMID- 27000727 TI - HLA mismatching as a strategy to reduce relapse after alternative donor transplantation. AB - Human leukocyte antigen (HLA) mismatches are targets of alloreactive T cells, mediators of graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) after alternative donor transplantation. Exploitation of HLA mismatching in order to reduce relapse is hampered by necessary interventions aimed at controlling GvHD on the one hand, and by the possibility of immune escape through selective loss of mismatched HLA in relapsing leukemia on the other. Retrospective studies reporting the impact of HLA mismatches on post-transplant relapse need to be interpreted with caution, due to many confounding factors, including disease and use of T-cell depletion, and to be constantly updated to the rapidly changing clinical protocols. Current evidence suggests similar relapse rates for 8/8, 7/8 HLA-matched unrelated, T-cell-replete haploidentical and umbilical cord blood transplantation; however, investigations of locus-specific effects are still scarce in the latter two settings. In unrelated transplantation, a specific role for mismatches at HLA-C and HLA-DPB1, and therein of permissive mismatches defined on the basis of T-cell alloreactivity and/or expression levels, in reducing relapse has been demonstrated in independent studies. This observation suggests new approaches to utilize HLA matching in unrelated donor searches, and the need for further research in the field. PMID- 27000728 TI - Alternative donors: cord blood for adults. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with hematological diseases. The probability of finding a human leukocyte antigen (HLA)- identical donor among family members is around 25% and 30% that of having a full matched unrelated donor in the registry. Patients in need may also benefit of a HLA-mismatched HSCT either from an haploidentical donors or from umbilical cord blood (UCB). Much has been learned about UCB transplant (UCBT) since the first human UCBT was performed back in 1988. Cord blood banks have been established worldwide for the collection, cryopreservation, and distribution of UCB for HSCT. Today, a global network of cord blood banks and transplant centers has been established with a large common inventory of more than 650,000 UCB units available, allowing for more than 40,000 UCBT worldwide in children and adults with severe hematological diseases. Several studies have been published on UCBT, assessing risk factors such as cell dose and HLA mismatch. Outcomes of several retrospective comparative studies showed similar results using other stem cell sources both in pediatric and adult setting. New strategies are ongoing to facilitate engraftment and reduce transplant-related mortality. In this issue, we review the current results of UCBT in adults with hematological malignancies and the clinical studies comparing UCBT with other transplant strategies. We provide guidelines for donor algorithm selection in UCBT setting. PMID- 27000729 TI - Transplantations from HLA-identical siblings versus 10/10 HLA-matched unrelated donors. AB - The clinical outcome after allogeneic stem cell transplantation from a human leukocyte antigen (HLA)-matched sibling donor as well as an HLA-matched unrelated donor has clearly improved due in part to the progress made in the domains of HLA typing techniques. Although HLA-matched sibling transplantation is still held as the "gold standard," transplantation from HLA-A, -B, -C, -DRB1, and -DQB1-matched unrelated donors (so called 10/10) represent the first choice for patients without a suitable related donor. Several studies have shown that unmanipulated marrow transplantation from an HLA allele-matched unrelated donor resulted in similar outcomes to those observed following sibling transplantation. However, incorporating anti-thymocyte globulin (ATG) within graft-versus-host disease (GVHD) prophylaxis should be considered for peripheral blood stem cell grafts in order to decrease the risk of developing chronic GVHD. PMID- 27000730 TI - Mismatched unrelated alternative donors for hematological malignancies. AB - For the majority of hematologic malignancies allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option. Sibling donors have been the standard for adult patients. Since there is not a suitable family donor for all patients, the need for alternative donors for HCT is great. Fortunately, the availability of unrelated volunteer donor registries has expanded over the years and the results of HCT with matched unrelated donors (MUD) are comparable to the results with matched related donors (MRD). Nevertheless, there are many patients lacking a well-matched donor. To increase the applicability of transplantation, alternative donors such as mismatched unrelated donors (MMURD), cord blood stem cell products and haploidentical related donors have been widely used. This review seeks to give insights into the use of MMUD donors for HCT and summarize the existing data. PMID- 27000731 TI - Haploidentical stem cell transplantation: anti-thymocyte globulin-based experience. AB - Haploidentical stem cell transplantation (haplo-SCT) with an anti-thymocyte globulin (ATG) preparative regimen is associated with induced immune tolerance, rapid hematopoietic recovery, effective prevention of graft-versus-host disease (GVHD), and lower non-relapse mortality (NRM). This has become a common and successfully applied protocol in patients with hematological diseases undergoing haplo-SCT. Survival rates among patients who undergo unmanipulated haploidentical blood and marrow transplantation (HBMT) with anti-thymocyte globulin (ATG)-based regimens are comparable to those following human leukocyte antigen (HLA)-matched sibling transplantation or unrelated donor transplantation. Unmanipulated HBMT can also be successfully used as a post-remission treatment algorithm for acute lymphoblastic leukemia (ALL) and adult acute myeloid leukemia (AML) in cases with unfavorable cytogenetics. Future investigations should focus on further improving donor selection, optimizing allografts, dealing with primary graft failure, and relapse prophylaxis and treatment. PMID- 27000733 TI - Cord blood versus haploidentical stem cell transplantation for hematological malignancies. AB - Umbilical cord blood (UCB) and haploidentical donor stem cell sources represent common alternative donor strategies used when a matched sibling donor (MRD) or matched unrelated donor (MUD) is not available for hematopoietic stem cell transplantation (HSCT). Both donor sources require less stringent human leukocyte antigen (HLA) matching and thereby increase the donor pool for patients without a complete HLA-matched donor. Although a randomized trial comparing these donor sources is ongoing, currently available comparisons rely on observational data and small phase II trials. In hematologic malignancies, both donor sources offer the chance of eradicating disease, albeit with different results for engraftment time, graft failure, graft-versus-host disease (GVHD), transplant-related mortality (TRM), and relapse risk. This review focuses on comparing those outcomes and providing clinicians with evidence to help guide the decision between these alternative donor sources. PMID- 27000732 TI - Haploidentical bone marrow and stem cell transplantation: experience with post transplantation cyclophosphamide. AB - Allogeneic blood or bone marrow transplantation (BMT) is a potentially curative therapy for high-risk hematologic malignancies not curable by standard chemotherapy, but the procedure is limited by the availability of human leukocyte antigen-matched donors for many patients, as well as toxicities including graft versus-host disease (GVHD). Our group has developed the use of high-dose post transplantation cyclophosphamide (PTCy) to selectively remove alloreactive T cells without compromising engraftment. This protocol has allowed for successful transplantation of human leukocyte antigen (HLA)-haploidentical (haplo) grafts, thus expanding the donor pool for the many patients who would not otherwise be a candidate for this life-saving procedure. In this review we will summarize the data that led to the development of PTCy, then focus on the outcomes of haploBMT trials with PTCy across different transplant platforms for patients with malignant hematologic diseases, and finally we will discuss emerging evidence that suggests equivalency of haploBMT with PTCy compared with more traditional transplants. PMID- 27000734 TI - Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias. AB - The availability of alternative sources of stem cells including most recently T replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). PMID- 27000735 TI - Haploidentical transplantation: selecting optimal conditioning regimen and stem cell source. AB - Recently, haploidentical donor transplant (HIDT) has emerged as a viable option for patients in need of an allogeneic stem cell transplant without an immediately available well-matched human leukocyte antigen (HLA) sibling or unrelated donor. Given the near immediate availability of haploidentical donors, along the high likelihood of a haploidentical match within a patient's first-degree family, HIDT is becoming increasing attractive, particularly for patients with high-risk disease. In the last decade, several strategies of T-cell-replete bone marrow or peripheral blood HIDT has been developed with diverse conditioning regimens and graft-versus-host disease prophylaxis based on diverse in vivo T-cell modulation strategies conducting to a wide development for the treatment of benign and malignant hematological disorders. Several conditioning, different stem cell sources, and graft-versus-host disease (GVHD) prophylaxis regimens have been designed by different groups at the same time. They all demonstrated the feasibility of such transplants with limited non-relapse mortality (NRM) and promising survival rates. However, comparative studies between the different transplant strategies had not been performed. Herein, we discuss the conditioning regimens and stem cell sources that have been used for haploidentical transplant. PMID- 27000736 TI - Alternative donor transplants for severe aplastic anemia: current experience. AB - Patients with acquired severe aplastic anemia (SAA), who lack a human leukocyte antigen (HLA) identical sibling donor (SIB), have two therapeutic options: immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine (CsA), or a transplant from an alternative donor. In these patients, the current guidelines of the European Group for Blood and Marrow Transplantation (EBMT) call for a course of ATG + CsA first and transplantation in case of no response. The alternative donor source can be an unrelated donor (UD), a cord blood (CB) unit, or a family mismatched member, in most instances genetically HLA haplo-mismatched (HAPLO). In the present review, we will discuss recent results of transplants from matched UD and SIB donors, with significantly improved outcome, especially with UD in the past decade. We will also be looking at CB transplants, and the problems of limited stem cell dose. Finally HAPLO grafts have been explored in patients lacking or having rejected an unrelated or CB graft: early results seem encouraging, though the procedure should still be considered experimental. PMID- 27000737 TI - Alternative donor allogeneic hematopoietic cell transplantation for hemoglobinopathies. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative therapy for patients with hemoglobinopathies, mainly severe sickle cell disease (SCD) and thalassemia (TM). However, the applicability of HSCT has been limited mainly by donor availability, with a less than 25%-30% of eligible patients having human leukocyte antigen (HLA)-matched sibling donors. Previous outcomes using alternate donor options have been markedly inferior due to increased regimen-related toxicity, transplant-related mortality, graft failure, and graft versus-host disease (GVHD). Advances in transplant technology, including high resolution HLA typing, improved GVHD prophylactic approaches with tolerance induction, and better supportive care over the last decade, are addressing these historical challenges, resulting in increasing donor options. Herein, we review alternate donor HSCT approaches for severe SCD and TM using unrelated donors, umbilical cord blood units, or related haploidentical donors. Though this is an emerging field, early results are promising and in selected patients, this may be the preferred option to mitigate against the age-related morbidity and early mortality associated with these disorders. PMID- 27000738 TI - Supportive care in alternative donor transplantation. AB - Alternative donor hematopoietic cell transplantation (HCT) using umbilical cord blood, haploidentical or mismatched unrelated donors is a viable option for patients without human leukocyte antigen (HLA)-identical sibling or matched unrelated donors. The same principles of supportive care as conventional graft sources apply to alternative donor HCT recipients. However, there are some unique supportive care issues related to post-transplant complications, engraftment, graft-versus-host disease, immune reconstitution, and infections that are unique to each of the three alternative graft sources, both in the early and late post transplant periods. This review discusses the supportive care issues relevant to this population and their management. PMID- 27000739 TI - Preparation of photonic-magnetic responsive molecularly imprinted microspheres and their application to fast and selective extraction of 17beta-estradiol. AB - Photonic-magnetic responsive molecularly imprinted microspheres (PM-MIMs) were prepared by seed polymerization, through suitable functionalization of magnetic nanoparticles for further coating with photoresponsive functional monomer and imprinted layers, and then were successfully applied to the fast and selective extraction of 17beta-estradiol (17beta-E2) from real samples. The PM-MIMs possessed a sandwich micro-spherical structure containing Fe3O4 core, SiO2 middle layer, and MIPs shell with thickness of 25 nm. The PM-MIMs displayed excellent photoresponsive properties and could be rapidly separated from solutions under an external magnet. The PM-MIMs had specific affinity towards 17beta-E2 with high adsorption capacity (Qmax=0.84 mg g(-1)) and fast binding kinetics (Kd=26.08 mg L(-1)). The PM-MIMs proved to be an ideal photoswitch with the ability of reversible uptake and release of 17beta-E2 upon alternate 365 and 440 nm irradiation: 45.0% of 17beta-E2 released from the PM-MIMs upon 365 nm irradiation, and 94.0% of the released 17beta-E2 was rebound to the PM-MIMs at 440 nm. Accordingly, the PM-MIMs were applied for fast separation and extraction of 17beta-E2 followed by HPLC-UV determination, presenting the low limit of detection (LOD, S/N=3) and quantification (LOQ, S/N=10) of 0.18 and 0.62 MUmol L( 1), respectively. The high recoveries for spiked milk powder and drinking water samples were in the range of 97.5-113.0% with relative standard deviations less than 4.4%. This study reasonably combined photonic response, magnetic separation and surface imprinting, which endowed the PM-MIMs with significant advantages of high adsorption capacity and fast binding kinetics, convenient separation and recycled use, and simple rapid eco-benign adsorption/elution processes for template molecules. Thus, the PM-MIMs based method may be a simple, rapid, convenient, cost-effective and environmentally-friendly way for simultaneous separation, enrichment and detection of trace 17beta-E2 in complicated matrices. PMID- 27000740 TI - Three-step stacking by field-enhanced sample injection, sweeping, and micelle to solvent stacking in capillary electrophoresis: Anionic analytes. AB - Three-step stacking by field-enhanced sample injection (FESI), sweeping, and micelle to solvent stacking (MSS) in co-EOF capillary zone electrophoresis (CZE) is presented for anionic analytes. Long FESI produced an overloaded stacked zone of analytes (four model penicillins). Sweeping of the FESI zone was by electrokinetic injection of cetyltrimethylammonium bromide (CTAB) micelles. MSS was by short injection of 60% methanol that released the swept analytes from CTAB micelles. The sensitivity enhancement factors were 146-279 and 519-954 for conductivity ratio of 10 and 100, respectively. The SEF enhancement factors (factor=SEF from three-step stacking/SEF from FESI) were 16-32 and 6-10, correspondingly. The LODs were between 6.6-13.2 ng/mL, repeatability (intraday and interday) was %RSD<=5.4%, and linearity was R(2)>=0.998. Application to real sample was investigated using fortified plasma after liquid-liquid extraction. PMID- 27000742 TI - Spectroscopic and kinetic evidence for redox cycling, catalase and degradation activities of Mn(III)(TPPS) in a basic aqueous peroxide medium. AB - Mn(III)(TPPS) was found to react rapidly with hydrogen peroxide in basic aqueous solution to form intermediate (TPPS)Mn(V)[double bond, length as m-dash]O and (TPPS)Mn(IV)[double bond, length as m-dash]O species which, in the presence of excess H2O2, are reduced fully back to Mn(III)(TPPS) with clear evidence for redox cycling of Mn(III)(TPPS). The system shows very strong catalase and degradation activities. PMID- 27000744 TI - Chemically functionalized germanene for spintronic devices: a first-principles study. AB - We have carried out first-principles calculations to explore various chemically functionalized germanene nanomaterials as two-dimensional spintronic devices. The germanene functionalized with O on one side and H on the other side is a ferromagnetic metal, and the phenomenon of negative differential conductance is observed. Moreover, we construct a spin-filter device from it, and about 15% spin filter efficiency is achieved in its ground state by using finite bias. The germanene semi-functionalized with a methyl (-CH3) group is a ferromagnetic semiconductor with a small direct bandgap, and it has highly spin-polarized electronic and transport properties. We proposed that a spin-valve nanodevice with a giant magnetoresistance of up to 10(7)% can be obtained from the semi methylated germanene nanostructure by introducing an achievable magnetic field to stabilize its metal-like ferromagnetic state. Our findings could be helpful for practical applications of two-dimensional germanane-based nanomaterials in spintronic devices in the future. PMID- 27000743 TI - Transgenesis in Strongyloides and related parasitic nematodes: historical perspectives, current functional genomic applications and progress towards gene disruption and editing. AB - Transgenesis for Strongyloides and Parastrongyloides was accomplished in 2006 and is based on techniques derived for Caenorhabditis elegans over two decades earlier. Adaptation of these techniques has been possible because Strongyloides and related parasite genera carry out at least one generation of free-living development, with adult males and females residing in soil contaminated by feces from an infected host. Transgenesis in this group of parasites is accomplished by microinjecting DNA constructs into the syncytia of the distal gonads of free living females. In Strongyloides stercoralis, plasmid-encoded transgenes are expressed in promoter-regulated fashion in the F1 generation following gene transfer but are silenced subsequently. Stable inheritance and expression of transgenes in S. stercoralis requires their integration into the genome, and stable lines have been derived from integrants created using the piggyBac transposon system. More direct investigations of gene function involving expression of mutant transgene constructs designed to alter intracellular trafficking and developmental regulation have shed light on the function of the insulin-regulated transcription factor Ss-DAF-16. Transgenesis in Strongyloides and Parastrongyloides opens the possibility of powerful new methods for genome editing and transcriptional manipulation in this group of parasites. Proof of principle for one of these, CRISPR/Cas9, is presented in this review. PMID- 27000745 TI - Polish and European management strategies in patients with atrial fibrillation. Data from the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot). AB - INTRODUCTION: Despite continued efforts of the European Society of Cardiology (ESC) to unify management of patients with atrial fibrillation (AF) across Europe, interregional differences in guideline adherence are likely. OBJECTIVES: The aim of the study was to compare treatment strategies depending on baseline characteristics of AF patients between Poland and other members of the European Union (EU). PATIENTS AND METHODS: We analyzed the baseline data and treatment strategies in participants of the ESC registry: the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. A total of 3119 consecutive patients with AF diagnosed within the last year were included in 67 centers from 9 countries, including 419 patients enrolled in 15 Polish centers. RESULTS: A rhythm control strategy was more frequent in Poland than in other EU countries (20.8% vs 11.9%; P <0.0001). Catheter ablation for AF was also used more frequently in Polish cardiology wards (13.9% vs 8.3%; P = 0.0017), while amiodarone at discharge was used less frequently (12.0% vs 22.7%; P <0.0001). In hospital use of vitamin K antagonists (VKAs) and non-VKA anticoagulants was less frequent in Polish patients with a CHA2DS2-VASc score of 2 or higher than in patients from other EU countries (61.1% vs 79.0%; P <0.0001), but overall anticoagulation rates at discharge were similar to those in other countries (83.3% vs 82.6%). CONCLUSIONS: A rhythm control-oriented strategy in patients with AF with the use of ablation in cardiology wards is more frequent in Poland than in other EU countries. Similar to other EU countries, compliance with the ESC guidelines regarding anticoagulation in AF patients is suboptimal in Poland. Undertreatment was observed in a significant proportion of patients at high risk of stroke, while a large group of low-risk patients are overtreated. Differences between the types of recruiting centers in Poland and other EU countries might have influenced the results. PMID- 27000747 TI - Steam burn on nose by heated, humidified high-flow nasal cannula in neonate. PMID- 27000746 TI - Comparing the short-term outcomes of intracorporeal esophagojejunostomy with extracorporeal esophagojejunostomy after laparoscopic total gastrectomy for gastric cancer. AB - BACKGROUND: Totally laparoscopic distal gastrectomy (TLDG) using intracorporeal anastomosis has gradually developed due to advancements in laparoscopic surgical instruments. However, totally laparoscopic total gastrectomy (TLTG) with intracorporeal esophagojejunostomy (IE) is still uncommon because of technical difficulties. Herein, we evaluated various types of IE after TLTG in terms of the technical aspects. We compared the short-term operative outcomes between TLTG with IE and laparoscopy-assisted total gastrectomy (LATG) with extracorporeal esophagojejunostomy (EE). METHODS: Between March 2006 and December 2014, a total of 213 patients with gastric cancer underwent TLTG and LATG. Overall, 92 patients underwent TLTG with IE, and 121 patients underwent LATG with EE. Generally, there are two methods of IE: mechanical staplers (circular or linear staplers) and hand sewn sutures. Surgical efficiencies and outcomes were compared between two groups. We also described various types of IE using a subgroup analysis. RESULTS: The mean operation times were similar in the two groups, as was the number of retrieved lymph nodes. However, the mean estimated blood loss of TLTG was statistically lower than LATG. There were no significant differences in time to first flatus, the time to restart oral intake, the length of the hospital stay after operation, and postoperative complications. Four types of IE have been applied after TLTG, including 42 cases of hand-sewn IE. The overall mean operation time and the mean anastomotic time in TLTG were 279.5 +/- 38.4 min and 52.6 +/- 18.9 min respectively. There was no case of conversion to open procedure. Postoperative complication occurred in 16 patients (17.4%) and no postoperative mortality occurred. CONCLUSIONS: IE is a feasible procedure and can be safely performed for TLTG with the proper laparoscopic expertise. It is technically feasible to perform hand-sewn IE after TLTG, which can reduce the cost of the laparoscopic procedure. PMID- 27000748 TI - Rejuvenating Muscle Stem Cell Function: Restoring Quiescence and Overcoming Senescence. AB - Elderly humans gradually lose strength and the capacity to repair skeletal muscle. Skeletal muscle repair requires functional skeletal muscle satellite (or stem) cells (SMSCs) and progenitor cells. Diminished stem cell numbers and increased dysfunction correlate with the observed gradual loss of strength during aging. Recent reports attribute the loss of stem cell numbers and function to either increased entry into a presenescent state or the loss of self-renewal capacity due to an inability to maintain quiescence resulting in stem cell exhaustion. Earlier work has shown that exposure to factors from blood of young animals and other treatments could restore SMSC function. However, cells in the presenescent state are refractory to the beneficial effects of being transplanted into a young environment. Entry into the presenescent state results from loss of autophagy, leading to increased ROS and epigenetic modification at the CDKN2A locus due to decreased H2Aub, upregulating cell senescence biomarker p16ink4a. However, the presenescent SMSCs can be rejuvenated by agents that stimulate autophagy, such as the mTOR inhibitor rapamycin. Autophagy plays a critical role in SMSC homeostasis. These results have implications for the development of senolytic therapies that attempt to destroy p16ink4a expressing cells, since such therapies would also destroy a reservoir of potentially rescuable regenerative stem cells. Other work suggests that in humans, loss of SMSC self-renewal capacity is primarily due to decreased expression of sprouty1. DNA hypomethylation at the SPRY1 gene locus downregulates sprouty1, causing inability to maintain quiescence and eventual exhaustion of the stem cell population. A unifying hypothesis posits that in aging humans, first loss of quiescence occurs, depleting the stem cell population, but that remaining SMSCs are increasingly subject to presenescence in the very old. PMID- 27000749 TI - A method of localization and segmentation of intervertebral discs in spine MRI based on Gabor filter bank. AB - BACKGROUND: Spine magnetic resonance image (MRI) plays a very important role in the diagnosis of various spinal diseases, such as disc degeneration, scoliosis, and osteoporosis. Accurate localization and segmentation of the intervertebral disc (IVD) in spine MRI can help accelerate the diagnosis time and assist in the treatment by providing quantitative parameters. In this paper, a method based on Gabor filter bank is proposed for IVD localization and segmentation. METHODS: First, the structural features of IVDs are extracted using a Gabor filter bank. Second, the Gabor features of spine are calculated and spinal curves are detected. Third, the Gabor feature images (GFI) of IVDs are calculated and adjusted according to the spinal curves. Fourth, the IVDs are localized by clustering analysis with GFI. Finally, an optimum grayscale-based algorithm with self-adaptive threshold, combined with the localization results and Gabor features of the spine, is performed for IVDs segmentation. RESULTS: The proposed method is verified by an MRI dataset consisting of 278 IVDs from 37 patients. The accuracy of localization is 98.23 % and the dice similarity index for segmentation evaluation is 0.9237. CONCLUSIONS: The proposed Gabor filter based method is effective for IVD localization and segmentation. It would be useful in computer-aided diagnosis of IVD diseases and computer-assisted spine surgery. PMID- 27000750 TI - Resveratrol Increases Osteoblast Differentiation In Vitro Independently of Inflammation. AB - Low-grade inflammation negatively affects bone. Resveratrol is a natural compound proven to possess both anti-inflammatory and bone protective properties. However, it is uncertain if the bone effects are mediated though anti-inflammatory effects. Firstly, we investigated if resveratrol affects proliferation and differentiation of human bone marrow-derived mesenchymal stem cells. Secondly, we investigated if inflammation negatively affects proliferation and differentiation, and if resveratrol counteracts this through anti-inflammatory effects. Mesenchymal stem cells were obtained from bone marrow aspiration in 13 healthy individuals and cultured towards the osteoblast cell lineage. The cells were stimulated with resveratrol, lipopolysaccharide (LPS), LPS + resveratrol, or vehicle (control) for 21 days. Compared to control, resveratrol decreased cell number by 35 % (p < 0.05) and induced differentiation (a 3-fold increase in alkaline phosphatase (p < 0.002), while P1NP and OPG showed similar trends). LPS induced inflammation with a 44-fold increase in interleukin-6 (p < 0.05) and an extremely prominent increase in interleukin-8 production (p < 0.05) relative to control. In addition, LPS increased cell count (p < 0.05) and decreased differentiation (a reduction in P1NP production (p < 0.02)). Co-stimulation with LPS + resveratrol did not reduce interleukin-6 or interleukin-8, but nonetheless, cell count was reduced (p < 0.05) and alkaline phosphatase, P1NP, and OPG increased (p < 0.05 for all). Thus, resveratrol stimulates osteoblast differentiation independently of inflammation. PMID- 27000751 TI - Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease. AB - Ulcerative colitis (UC) and Crohn's disease (CD) are diseases affecting the gastrointestinal tract. Treatment depends on the severity of the disease, site of inflammation, and patient's response. The aim of this study was to develop a zero order sustained-release tablet containing both the anti-inflammatory drugs mesalazine and budesonide as a new treatment option for ileo-colonic CD and UC. Tablets were attained by wet granulation with hydroxypropyl methylcellulose and direct compression. Our newly developed tablet core was coated with different ColoPulse(r) coating thicknesses and the mesalazine and budesonide release profiles were investigated in a 600-min gastrointestinal simulation system (GISS) experiment, together with commercially available MMX(r)-mesalazine and MMX(r) budesonide. Lag-time, release rate (k0), completeness of release, and zero-order correlation coefficient (R(2)0) could be manipulated by varying ColoPulse(r) coating thickness. Our newly developed combination preparation (C[4.92]) complied with all conducted European Pharmacopoeia tests as well as an accelerated 6-month stability test and had a lag-time of 250min (simulated ileum targeted), a linear release profile (mesalazine R(2)0=0.9002; budesonide R(2)0=0.9481), and drug release of 100% mesalazine and 77% budesonide. Like C[4.92], MMX(r)-mesalazine had a linear (R(2)0=0.9883) and complete release profile (96%). However, C[4.92] lag-time was longer (250 vs. 210min), assuring simulated ileum specificity. Remarkably, MMX(r)-budesonide lag-time was 480min and release was only 7% with a linear character (R(2)0=0.9906). The in vitro results suggest that MMX(r) budesonide effectiveness may be improved if budesonide release in the aqueous phase would be increased and that C[4.92] is a potential, new treatment option for ileo-colonic CD and UC. PMID- 27000752 TI - Improving gross anatomy learning using reciprocal peer teaching. AB - BACKGROUND: The use of cadavers in human anatomy teaching requires adequate number of anatomy instructors who can provide close supervision of the students. Most medical schools are facing challenges of lack of trained individuals to teach anatomy. Innovative techniques are therefore needed to impart adequate and relevant anatomical knowledge and skills. This study was conducted in order to evaluate the traditional teaching method and reciprocal peer teaching (RPT) method during anatomy dissection. METHODS: Debriefing surveys were administered to the 227 first year medical students regarding merits, demerits and impact of both RPT and Traditional teaching experiences on student's preparedness prior to dissection, professionalism and communication skills. Out of this, 159 (70 %) completed the survey on traditional method while 148 (65.2 %) completed survey on RPT method. An observation tool for anatomy faculty was used to assess collaboration, professionalism and teaching skills among students. Student's scores on examinations done before introduction of RPT were compared with examinations scores after introduction of RPT. RESULTS: Our results show that the mean performance of students on objective examinations was significantly higher after introduction of RPT compared to the performance before introduction of RPT [63.7 +/- 11.4 versus 58.6 +/- 10, mean difference 5.1; 95 % CI = 4.0-6.3; p value < 0.0001]. Students with low performance prior to RPT benefited more in terms of examination performance compared to those who had higher performance [Mean difference 7.6; p-value < 0.0001]. Regarding student's opinions on traditional method versus RPT, 83 % of students either agreed or strongly agreed that they were more likely to read the dissection manual before the RPT dissection session compared to 35 % for the traditional method. Over 85 % of respondents reported that RPT improved their confidence and ability to present information to peers and faculty compared to 38 % for the tradition method. The majority of faculty reported that the learning environment of the dissection groups was very active learning during RPT sessions and that professionalism was observed by most students during discussions. CONCLUSIONS: Introduction of RPT in our anatomy dissection laboratory was generally beneficial to both students and faculty. Both objective (student performance) and subjective data indicate that RPT improved student's performance and had a positive learning experience impact. Our future plan is to continue RPT practice and continually evaluate the RPT protocol. PMID- 27000753 TI - Effect of continuous positive airway pressure treatment on pulmonary artery pressure in patients with isolated obstructive sleep apnea: a meta-analysis. AB - Pulmonary hypertension (PH) can occur in patients with obstructive sleep apnea (OSA) in the absence of cardiac or lung disease. Data on the development and severity of PH, and the effect of continuous positive airway pressure (CPAP) therapy on pulmonary artery (PA) pressures in these patients have been inconsistent in the literature. We sought to determine whether CPAP therapy affects PA pressures in patients with isolated OSA in this meta-analysis. We searched PubMed, Medline, EMBASE and other databases from January 1980 to August 2015. Studies of patients with OSA, defined as an apnea-hypopnea index >10 events/h, and PH, defined as PA pressure >25 mmHg were included. Two reviewers independently extracted data and assessed risk of bias. A total of 222 patients from seven studies (341.53 person-years) had reported PA pressures before and after treatment with CPAP therapy. 77 % of participants were men, with a mean age of 52.5 years, a mean apnea-hypopnea index of 58 events/h, and mean PA pressure of 39.3 +/- 6.3 mmHg. CPAP treatment duration ranged from 3 to 70 months. Using fixed effects meta-analysis, CPAP therapy was associated with a decrease in PA pressure of 13.3 mmHg (95 % CI 12.7-14.0) in our study population. This meta analysis found that CPAP therapy is associated with a significantly lower PA pressure in patients with isolated OSA and PH. PMID- 27000755 TI - Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia. AB - Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were markedly higher than those of U937 and KG-1alpha. In contrast, silencing of EZH2 resulted in reduction in proliferation and migration ability and an increase in apoptosis. The latter observation was accompanied by reduced expression of associated proteins p-ERK, p cmyc, and matrix metalloproteinase 2 (MMP-2) and an increase in epithelial cadherin (E-cadherin). These data suggest that higher expression of EZH2 may be associated with extramedullary infiltration in acute myeloid leukemia and affect pathogenesis via activation of the p-ERK/p-cmyc/MMP-2 and E-cadherin signaling pathways. PMID- 27000756 TI - Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis. AB - Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by the development of hundreds to thousands of colonic adenomas and an increased risk of colorectal cancer. Adenomatous polyposis coli (APC), encoding a large multidomain protein involved in antagonizing the Wnt signaling pathway, has been identified as the main causative gene responsible for FAP. In this study, we identified three novel mutations as well as two recurrent mutations in the APC in five Chinese FAP families by sequencing. Immunohistochemical analysis revealed that among these mutations, a nonsense mutation (c.2510C>G) and two small deletions (c.2016_2047del, c.3180_3184del) led to the truncation of the APC protein and the cytoplasmic and nuclear accumulation of beta-catenin in the colorectal samples from affected individuals, respectively. Our study expands the database on mutations of APC and provides evidence to understand the function of APC in FAP. PMID- 27000754 TI - Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology. AB - Inspiratory function is essential for alveolar ventilation and expulsive behaviors that promote airway clearance (e.g., coughing and sneezing). Current evidence demonstrates that inspiratory dysfunction occurs during healthy aging and is accentuated by chronic heart failure (CHF). This inspiratory dysfunction contributes to key aspects of CHF and aging cardiovascular and pulmonary pathophysiology including: (1) impaired airway clearance and predisposition to pneumonia; (2) inability to sustain ventilation during physical activity; (3) shallow breathing pattern that limits alveolar ventilation and gas exchange; and (4) sympathetic activation that causes cardiac arrhythmias and tissue vasoconstriction. The diaphragm is the primary inspiratory muscle; hence, its neuromuscular integrity is a main determinant of the adequacy of inspiratory function. Mechanistic work within animal and cellular models has revealed specific factors that may be responsible for diaphragm neuromuscular abnormalities in CHF and aging. These include phrenic nerve and neuromuscular junction alterations as well as intrinsic myocyte abnormalities, such as changes in the quantity and quality of contractile proteins, accelerated fiber atrophy, and shifts in fiber type distribution. CHF, aging, or CHF in the presence of aging disturbs the dynamics of circulating factors (e.g., cytokines and angiotensin II) and cell signaling involving sphingolipids, reactive oxygen species, and proteolytic pathways, thus leading to the previously listed abnormalities. Exercise-based rehabilitation combined with pharmacological therapies targeting the pathways reviewed herein hold promise to treat diaphragm abnormalities and inspiratory muscle dysfunction in CHF and aging. PMID- 27000757 TI - Pharmacokinetics of Melatonin: The Missing Link in Clinical Efficacy? AB - Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t max value of 30-45 min and a t 1/2elimination of 45 min are well established. Several questions relate to what constitutes a clinically effective plasma concentration, the choice of ideal administration route, and the optimal method of analysis. Furthermore, investigations of melatonin metabolites in humans are urgently needed in order to characterize their biological functions and the metabolic fates of these derivatives. Finally, pharmacokinetics in patients should be investigated further in order to reduce the risk of potential adverse effects, such as daytime sleepiness or unintended sedation. PMID- 27000758 TI - Dose- and Formulation-Dependent Non-Linear Pharmacokinetic Model of Paritaprevir, a Protease Inhibitor for the Treatment of Hepatitis C Virus Infection: Combined Analysis from 12 Phase I Studies. AB - BACKGROUND AND OBJECTIVES: Paritaprevir is a direct-acting antiviral agent that is a component of approved multidrug regimens used in the treatment of hepatitis C virus (HCV) infection. A population pharmacokinetic model for paritaprevir was developed using data from formulation, bioavailability, and drug-drug interaction studies that evaluated the pharmacokinetics of paritaprevir (coadministered with ritonavir to enhance exposure) with or without ombitasvir and/or dasabuvir at different paritaprevir dose levels. METHODS: A non-linear mixed-effects modeling approach was applied to data from 12 phase I, single- and multiple-dose studies that enrolled a total of 369 healthy volunteers. Age, sex, race, ethnicity, body weight, body surface area, body mass index, and baseline creatinine clearance were evaluated as covariates during model development. In addition, the influences of dose, formulation, and concomitant medications (e.g. ombitasvir and dasabuvir) on paritaprevir bioavailability were included in the model. RESULTS: A two-compartment model with first-order absorption and elimination optimally described paritaprevir plasma concentration-time data. Paritaprevir bioavailability was formulation- and dose-dependent, and increased supraproportionally. The accumulation of paritaprevir was 1.57-fold on repeated dosing compared with the first dose. Coadministration of dasabuvir increased paritaprevir bioavailability by 59 %; however, ombitasvir coadministration did not affect the pharmacokinetic profile of paritaprevir. No subject-specific covariate influenced the paritaprevir pharmacokinetics. The pharmacokinetic model was robust in bootstrap evaluations and was consistent with observed data based on diagnostic goodness-of-fit plots and visual predictive checks. CONCLUSION: The complex pharmacokinetics of paritaprevir were well described by the model, which can be used as a basis for clinical trial dosing and further evaluations in patients with HCV. PMID- 27000759 TI - Author's reply to Veloso HH Comment on "The Role of Digitalis Pharmacokinetics in Converting Atrial Fibrillation and Flutter to Sinus Rhythm". PMID- 27000760 TI - Comment on: "The Role of Digitalis Pharmacokinetics in Converting Atrial Fibrillation and Flutter to Sinus Rhythm". PMID- 27000761 TI - Surgery for intracranial arachnoid cysts in children-a prospective long-term study. AB - PURPOSE: Intracranial arachnoid cysts are cystic malformations found in both adults and children. While many are asymptomatic, some cause symptoms and warrant surgical treatment. In this prospective population-based study, we aimed to study the short- and long-term outcome after surgical intervention in children with arachnoid cysts referred to our centre. METHODS: Twenty-seven pediatric patients (13 f. 14 m, mean age 9.4 years) with de novo cysts were consecutively included during a 5-year period. The presenting symptoms were headache (n = 12), balance disturbance and dizziness (n = 6), seizures (n = 6), hydrocephalus (n = 5), and macrocephaly (n = 1). Twenty-two patients underwent surgical treatment with either microsurgical (n = 17) or endoscopic fenestration (n = 5) of the cyst wall. Cyst volume was measured with OsiriX(r) software pre- and postoperatively. Short-term and long-term follow-up of all patients was conducted 3 months and 8.6 years (7-10.5 years) postoperatively. RESULTS: Three months after surgery, 59 % of the patients were improved regarding at least one major complaint, and average cyst volume was reduced to 33.3 ml (0-145 ml). At the long-term follow-up of 8.6 years, 77 % of the patients were improved regarding at least one symptom but subjective symptoms remained in 59 %. There was no permanent postoperative morbidity. We found no association between radiological reduction of cyst volume and clinical improvement. CONCLUSION: Our findings support a restrictive attitude to surgery for intracranial arachnoid cysts, in the absence of objectively verified symptoms and signs or obstruction of CSF pathways. PMID- 27000762 TI - Multidisciplinary assessment of congenital insensitivity to pain syndrome. AB - BACKGROUND: Congenital insensitivity to pain and anhidrosis (CIPA) is a rare clinical condition characterized by the absence of normal subjective and objective responses to noxious stimuli in patients with intact central and peripheral nervous systems. CASE PRESENTATIONS: Two patients with CIPA are reported. The first patient was a 13-year-old girl who presented to our hospital with multiple joint destructions secondary to osteomyelitis. The second patient was a 10-year-old boy who presented with multiple hand lesions and right leg osteomyelitis. Our patients were treated with multiple debridements and intravenous antibiotics according to our hospital protocol. CONCLUSION: Early recognition of the disease is important. The treatment for this condition is focused more on the prevention of bone injuries and joint infection, as opposed to a cure. There are no standard techniques or guidelines available to treat this rare disease. Overall, effective CIPA treatment is built around family education and patient training. PMID- 27000763 TI - A practical 3D printed simulator for endoscopic endonasal transsphenoidal surgery to improve basic operational skills. AB - PURPOSE: We aimed to present a practical three-dimensional (3D) printed simulator to comprehensively and effectively accelerate the learning curve of endoscopic endonasal transsphenoidal surgery (EETS). METHODS: The 3D printed simulator consists of three parts: (1) skull frame, (2) the nasal passage and the nasal alar of the face, and (3) a modified sella turcica. We aimed to improve three basic operational skills of surgeons: drilling, curetting, and aspirating. Eighteen neurosurgeons and five post-graduates were recruited and consented for the training. RESULTS: For trainees, (1) as the training progressed, the scores increased gradually, (2) a significant increase in the average scores was observed in the tenth training compared to the first training, and (3) there is a significant decrease in trainee variability in the shortening of the gap. The 18 neurosurgeons were divided into three groups: experts, assistants, and observers. For all three basic operations, (1) the average score of experts was obviously higher than that of the assistants, observers, and trainees' tenth training and (2) the average scores of assistants and observers were obviously higher than that of trainees' first training. A significant high in the average score between the assistants and the observers was seen for aspirating, but not for drilling or curetting. For curetting and aspirating, the tenth training average score of trainees was obviously higher than that of assistants and observers. CONCLUSION: This 3D printed simulator allows different endoscopic basic operations to be simulated and improves the EETS techniques of surgeons. We believed it to be a practical, simple, and low-cost simulator. PMID- 27000764 TI - Randomized, Blinded Pilot Testing of Nonconventional Stimulation Patterns and Shapes in Parkinson's Disease and Essential Tremor: Evidence for Further Evaluating Narrow and Biphasic Pulses. AB - OBJECTIVES: Evidence suggests that nonconventional programming may improve deep brain stimulation (DBS) therapy for movement disorders. The primary objective was to assess feasibility of testing the tolerability of several nonconventional settings in Parkinson's disease (PD) and essential tremor (ET) subjects in a single office visit. Secondary objectives were to explore for potential efficacy signals and to assess the energy demand on the implantable pulse-generators (IPGs). MATERIALS AND METHODS: A custom firmware (FW) application was developed and acutely uploaded to the IPGs of eight PD and three ET subjects, allowing delivery of several nonconventional DBS settings, including narrow pulse widths, square biphasic pulses, and irregular pulse patterns. Standard clinical rating scales and several objective measures were used to compare motor outcomes with sham, clinically-optimal and nonconventional settings. Blinded and randomized testing was conducted in a traditional office setting. RESULTS: Overall, the nonconventional settings were well tolerated. Under these conditions it was also possible to detect clinically-relevant differences in DBS responses using clinical rating scales but not objective measures. Compared to the clinically optimal settings, some nonconventional settings appeared to offer similar benefit (e.g., narrow pulse widths) and others lesser benefit. Moreover, the results suggest that square biphasic pulses may deliver greater benefit. No unexpected IPG efficiency disadvantages were associated with delivering nonconventional settings. CONCLUSIONS: It is feasible to acutely screen nonconventional DBS settings using controlled study designs in traditional office settings. Simple IPG FW upgrades may provide more DBS programming options for optimizing therapy. Potential advantages of narrow and biphasic pulses deserve follow up. PMID- 27000766 TI - Nanocarbon Allotropes-Graphene and Nanocrystalline Diamond-Promote Cell Proliferation. AB - Two profoundly different carbon allotropes - nanocrystalline diamond and graphene - are of considerable interest from the viewpoint of a wide range of biomedical applications including implant coating, drug and gene delivery, cancer therapy, and biosensing. Osteoblast adhesion and proliferation on nanocrystalline diamond and graphene are compared under various conditions such as differences in wettability, topography, and the presence or absence of protein interlayers between cells and the substrate. The materials are characterized in detail by means of scanning electron microscopy, atomic force microscopy, photoelectron spectroscopy, Raman spectroscopy, and contact angle measurements. In vitro experiments have revealed a significantly higher degree of cell proliferation on graphene than on nanocrystalline diamond and a tissue culture polystyrene control material. Proliferation is promoted, in particular, by hydrophobic graphene with a large number of nanoscale wrinkles independent of the presence of a protein interlayer, i.e., substrate fouling is not a problematic issue in this respect. Nanowrinkled hydrophobic graphene, thus, exhibits superior characteristics for those biomedical applications where high cell proliferation is required under differing conditions. PMID- 27000765 TI - Sensitivity and correlation of hypervariable regions in 16S rRNA genes in phylogenetic analysis. AB - BACKGROUND: Prokaryotic 16S ribosomal RNA (rRNA) sequences are widely used in environmental microbiology and molecular evolution as reliable markers for the taxonomic classification and phylogenetic analysis of microbes. Restricted by current sequencing techniques, the massive sequencing of 16S rRNA gene amplicons encompassing the full length of genes is not yet feasible. Thus, the selection of the most efficient hypervariable regions for phylogenetic analysis and taxonomic classification is still debated. In the present study, several bioinformatics tools were integrated to build an in silico pipeline to evaluate the phylogenetic sensitivity of the hypervariable regions compared with the corresponding full length sequences. RESULTS: The correlation of seven sub-regions was inferred from the geodesic distance, a parameter that is applied to quantitatively compare the topology of different phylogenetic trees constructed using the sequences from different sub-regions. The relationship between different sub-regions based on the geodesic distance indicated that V4-V6 were the most reliable regions for representing the full-length 16S rRNA sequences in the phylogenetic analysis of most bacterial phyla, while V2 and V8 were the least reliable regions. CONCLUSIONS: Our results suggest that V4-V6 might be optimal sub-regions for the design of universal primers with superior phylogenetic resolution for bacterial phyla. A potential relationship between function and the evolution of 16S rRNA is also discussed. PMID- 27000768 TI - Metal-Free Tandem Oxidative Coupling of Primary Alcohols with Azoles for the Synthesis of Hemiaminal Ethers. AB - A novel metal-free tandem oxidative coupling process for the synthesis of hemiaminal ethers has been developed. This protocol could be applied for the C-N bond formation of electron-deficient trizoles, tetrazoles, carbazoles and indazoles with primary alcohols. PMID- 27000767 TI - Bayesian risk profiling of soil-transmitted helminth infections and estimates of preventive chemotherapy for school-aged children in Cote d'Ivoire. AB - BACKGROUND: Soil-transmitted helminthiasis affects more than a billion people in the world and accounts for a global burden of 5.1 million disability-adjusted life years. The objectives of this study were (i) to map and predict the risk of soil-transmitted helminth infections among school-aged children in Cote d'Ivoire; (ii) to estimate school-aged children population-adjusted risk; and (iii) to estimate annual needs for preventive chemotherapy. METHODS: In late 2011/early 2012, a cross-sectional survey was carried out among school-aged children in 92 localities of Cote d'Ivoire. Children provided a single stool sample that was subjected to duplicate Kato-Katz thick smears for the diagnosis of soil transmitted helminths. A Bayesian geostatistical variable selection approach was employed to identify environmental and socioeconomic risk factors for soil transmitted helminth infections. Bayesian kriging was used to predict soil transmitted helminth infections on a grid of 1 * 1 km spatial resolution. The number of school-aged children infected with soil-transmitted helminths and the amount of doses needed for preventive chemotherapy according to World Health Organization guidelines were estimated. RESULTS: Parasitological data were available from 5246 children aged 5-16 years. Helminth infections with hookworm were predominant (17.2 %). Ascaris lumbricoides and Trichuris trichiura were rarely found; overall prevalences were 1.9 % and 1.2 %, respectively. Bayesian geostatistical variable selection identified rural setting for hookworm, soil acidity and soil moisture for A. lumbricoides, and rainfall coefficient of variation for T. trichiura as main predictors of infection. The estimated school aged children population-adjusted risk of soil-transmitted helminth infection in Cote d'Ivoire is 15.5 % (95 % confidence interval: 14.2-17.0 %). We estimate that approximately 1.3 million doses of albendazole or mebendazole are required for school-based preventive chemotherapy, and we provide school-aged children adjusted risk aggregated at health district level. CONCLUSION: We provide the first soil-transmitted helminthiasis risk profile for entire Cote d'Ivoire, based on a robust Bayesian geostatistical framework. Our model-based estimates of treatment needs and risk maps on health district level may guide the national control program in spatial targeting of annual interventions. PMID- 27000770 TI - Overcoming drug resistance to receptor tyrosine kinase inhibitors: Learning from lung cancer. AB - There are various receptor tyrosine kinase (TK)-targeted drugs that are currently used in the treatment of patients with non-small cell lung cancer (NSCLC). Among them, the epidermal growth factor receptor (EGFR) TK inhibitors (TKIs) are the most extensively studied. Receptor TKIs including EGFR TKIs have shown dramatic therapeutic efficacies in malignant tumors, which harbor activating mutations in the EGFR gene. However, within 1 or 2years after treatment, patients harboring these mutations often develop resistance to TKI therapy. This review article is aimed at drawing attention to the fact that we must first understand how receptor TKI resistance is acquired to develop strategies for overcoming resistance to TKIs. Furthermore, an insight into the specific molecules or signaling pathways that mediate resistance is a key factor for understanding and overcoming acquired drug resistance. Finally, we present our views on the continuing battle against "drug resistance," and provide further guidelines and strategies on how to minimize the development of drug-resistant tumors. PMID- 27000771 TI - Influence of different instrumentation modalities on the surface characteristics and biofilm formation on dental implant neck, in vitro. AB - OBJECTIVES: To evaluate surface characteristics of implants after using different instruments and biofilm formation following instrumentation. MATERIAL AND METHODS: Thirty-five commercially available dental implants were embedded into seven plastic models, attached to a phantom head and randomly assigned to seven instrumentation groups: (1) stainless steel (SSC) or (2) titanium curettes (TC); air-polisher using glycine-based (3) perio (PP) or (4) soft (SP) powders or (5) erythritol powder (EP); and an ultrasonic device using (6) stainless steel (PS) or (7) plastic-coated instruments (PI). Half of each implant neck in each group (n = 5) was treated once (30 s), while the other half was left uninstrumented (control). An eighth (8) treatment group used a bur/polisher to smooth two implants (SM). Following instrumentation implants were rinsed (5 ml Ringer's solution), analysed under a scanning electron microscope (SEM) and subjected twice (separately) to bacterial colonization with Streptococcus gordonii (2 h) and a mixed culture (S. gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, Porphyromonas gingivalis and Tannerella forsythia; 24 h). RESULTS: Visual assessment of SEM pictures revealed surface modifications (smoothening to roughening) following instrumentation. These alterations differed between the instrument groups and from the control. Quantitative scoring of the photographs revealed that SSC caused a significantly rougher surface compared to other instruments (P < 0.05), except for SP (P = 0.057) and PP (P = 0.108). After bacterial colonization no significant differences (P > 0.05) were evident between instrumented or control surfaces in either culture. CONCLUSIONS: Overall, no significant differences were observed in the surface characteristics (except for SSC) or bacterial colonization based on one-time instrumentation. PMID- 27000772 TI - Bayesian model selection framework for identifying growth patterns in filamentous fungi. AB - This paper describes a rigorous methodology for quantification of model errors in fungal growth models. This is essential to choose the model that best describes the data and guide modeling efforts. Mathematical modeling of growth of filamentous fungi is necessary in fungal biology for gaining systems level understanding on hyphal and colony behaviors in different environments. A critical challenge in the development of these mathematical models arises from the indeterminate nature of their colony architecture, which is a result of processing diverse intracellular signals induced in response to a heterogeneous set of physical and nutritional factors. There exists a practical gap in connecting fungal growth models with measurement data. Here, we address this gap by introducing the first unified computational framework based on Bayesian inference that can quantify individual model errors and rank the statistical models based on their descriptive power against data. We show that this Bayesian model comparison is just a natural formalization of Occam's razor. The application of this framework is discussed in comparing three models in the context of synthetic data generated from a known true fungal growth model. This framework of model comparison achieves a trade-off between data fitness and model complexity and the quantified model error not only helps in calibrating and comparing the models, but also in making better predictions and guiding model refinements. PMID- 27000773 TI - Improving the microbial community reconstruction at the genus level by multiple 16S rRNA regions. AB - BACKGROUND: 16S rRNA genes have been widely used for phylogenetic reconstruction and the quantification of microbial diversity through the application of next generation sequencing technology. However, long-read sequencing is still costly, while short-read sequencing carries less information for complex microbial community profiling; therefore, the applications of high throughput sequencing platforms still remain challenging in microbial community reconstruction analysis. RESULTS: Here, we developed a method to investigate the profile of aligned 16S rRNA gene sequences and to measure the proper region for microbial community reconstruction, as a step in creating a more efficient way to detect microorganism at the genus level. Finally, we found that each genus has its own preferential genus-specific amplicons for a genus assignment, which are not always located in hyper variable regions (HVRs). It was also noted that the rare genera should contribute less than dominant ones to the common profile of the aligned 16S rRNA sequences and have lower affinity to the common universal primer. CONCLUSIONS: Therefore, using multiple 16S rRNA regions rather than one "universal" region can significantly improve the ability of microbial community reconstruction. In addition, we found that a short fragment is suitable for most genera identifications, and the proper conserved regions used for primer design are larger than before. PMID- 27000774 TI - Mem-ADSVM: A two-layer multi-label predictor for identifying multi-functional types of membrane proteins. AB - Identifying membrane proteins and their multi-functional types is an indispensable yet challenging topic in proteomics and bioinformatics. However, most of the existing membrane-protein predictors have the following problems: (1) they do not predict whether a given protein is a membrane protein or not; (2) they are limited to predicting membrane proteins with single-label functional types but ignore those with multi-functional types; and (3) there is still much room for improvement for their performance. To address these problems, this paper proposes a two-layer multi-label predictor, namely Mem-ADSVM, which can identify membrane proteins (Layer I) and their multi-functional types (Layer II). Specifically, given a query protein, its associated gene ontology (GO) information is retrieved by searching a compact GO-term database with its homologous accession number. Subsequently, the GO information is classified by a binary support vector machine (SVM) classifier to determine whether it is a membrane protein or not. If yes, it will be further classified by a multi-label multi-class SVM classifier equipped with an adaptive-decision (AD) scheme to determine to which functional type(s) it belongs. Experimental results show that Mem-ADSVM significantly outperforms state-of-the-art predictors in terms of identifying both membrane proteins and their multi-functional types. This paper also suggests that the two-layer prediction architecture is better than the one layer for prediction performance. For reader's convenience, the Mem-ADSVM server is available online at http://bioinfo.eie.polyu.edu.hk/MemADSVMServer/. PMID- 27000775 TI - Erratum to: An Up-regulation of IRF-1 After a Spinal Cord Injury: Implications for Neuronal Apoptosis. PMID- 27000769 TI - Emerging therapeutic targets in metastatic progression: A focus on breast cancer. AB - Metastasis is the underlying cause of death for the majority of breast cancer patients. Despite significant advances in recent years in basic research and clinical development, therapies that specifically target metastatic breast cancer remain inadequate, and represents the single greatest obstacle to reducing mortality of late-stage breast cancer. Recent efforts have leveraged genomic analysis of breast cancer and molecular dissection of tumor-stromal cross-talk to uncover a number of promising candidates for targeted treatment of metastatic breast cancer. Rational combinations of therapeutic agents targeting tumor intrinsic properties and microenvironmental components provide a promising strategy to develop precision treatments with higher specificity and less toxicity. In this review, we discuss the emerging therapeutic targets in breast cancer metastasis, from tumor-intrinsic pathways to those that involve the host tissue components, including the immune system. PMID- 27000778 TI - A Secure Cloud-Assisted Wireless Body Area Network in Mobile Emergency Medical Care System. AB - Recent advances in medical treatment and emergency applications, the need of integrating wireless body area network (WBAN) with cloud computing can be motivated by providing useful and real time information about patients' health state to the doctors and emergency staffs. WBAN is a set of body sensors carried by the patient to collect and transmit numerous health items to medical clouds via wireless and public communication channels. Therefore, a cloud-assisted WBAN facilitates response in case of emergency which can save patients' lives. Since the patient's data is sensitive and private, it is important to provide strong security and protection on the patient's medical data over public and insecure communication channels. In this paper, we address the challenge of participant authentication in mobile emergency medical care systems for patients supervision and propose a secure cloud-assisted architecture for accessing and monitoring health items collected by WBAN. For ensuring a high level of security and providing a mutual authentication property, chaotic maps based authentication and key agreement mechanisms are designed according to the concept of Diffie-Hellman key exchange, which depends on the CMBDLP and CMBDHP problems. Security and performance analyses show how the proposed system guaranteed the patient privacy and the system confidentiality of sensitive medical data while preserving the low computation property in medical treatment and remote medical monitoring. PMID- 27000777 TI - A decision support system to improve medical diagnosis using a combination of k medoids clustering based attribute weighting and SVM. AB - The use of machine learning tools has become widespread in medical diagnosis. The main reason for this is the effective results obtained from classification and diagnosis systems developed to help medical professionals in the diagnosis phase of diseases. The primary objective of this study is to improve the accuracy of classification in medical diagnosis problems. To this end, studies were carried out on 3 different datasets. These datasets are heart disease, Parkinson's disease (PD) and BUPA liver disorders. Key feature of these datasets is that they have a linearly non-separable distribution. A new method entitled k-medoids clustering-based attribute weighting (kmAW) has been proposed as a data preprocessing method. The support vector machine (SVM) was preferred in the classification phase. In the performance evaluation stage, classification accuracy, specificity, sensitivity analysis, f-measure, kappa statistics value and ROC analysis were used. Experimental results showed that the developed hybrid system entitled kmAW + SVM gave better results compared to other methods described in the literature. Consequently, this hybrid intelligent system can be used as a useful medical decision support tool. PMID- 27000779 TI - Presence of pathogenic Escherichia coli is correlated with bacterial community diversity and composition on pre-harvest cattle hides. AB - BACKGROUND: Since 1982, specific serotypes of Shiga toxin-producing Escherichia coli (STEC) have been recognized as significant foodborne pathogens acquired from contaminated beef and, more recently, other food products. Cattle are the major reservoir hosts of these organisms, and while there have been advancements in food safety practices and industry standards, STEC still remains prevalent within beef cattle operations with cattle hides implicated as major sources of carcass contamination. To investigate whether the composition of hide-specific microbial communities are associated with STEC prevalence, 16S ribosomal RNA (rRNA) bacterial community profiles were obtained from hide and fecal samples collected from a large commercial feedlot over a 3-month period. These community data were examined amidst an extensive collection of prevalence data on a subgroup of STEC that cause illness in humans, referred to as enterohemorrhagic E. coli (EHEC). Fecal 16S rRNA gene OTUs (operational taxonomic units) were subtracted from the OTUs found within each hide 16S rRNA amplicon library to identify hide-specific bacterial populations. RESULTS: Comparative analysis of alpha diversity revealed a significant correlation between low bacterial diversity and samples positive for the presence of E. coli O157:H7 and/or the non-O157 groups: O26, O111, O103, O121, O45, and O145. This trend occurred regardless of diversity metric or fecal OTU presence. The number of EHEC serogroups present in the samples had a compounding effect on the inverse relationship between pathogen presence and bacterial diversity. Beta diversity data showed differences in bacterial community composition between samples containing O157 and non-O157 populations, with certain OTUs demonstrating significant changes in relative abundance. CONCLUSIONS: The cumulative prevalence of the targeted EHEC serogroups was correlated with low bacterial community diversity on pre-harvest cattle hides. Understanding the relationship between indigenous hide bacterial communities and populations may provide strategies to limit EHEC in cattle and provide biomarkers for EHEC risk assessment. PMID- 27000776 TI - The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age. AB - BACKGROUND: The rapid lengthening of life expectancy has raised the problem of providing social programs to counteract the age-related cognitive decline in a growing number of older people. Physical activity stands among the most promising interventions aimed at brain wellbeing, because of its effective neuroprotective action and low social cost. The purpose of this review is to describe the neuroprotective role exerted by physical activity in different life stages. In particular, we focus on adult neurogenesis, a process which has proved being highly responsive to physical exercise and may represent a major factor of brain health over the lifespan. METHODS: The most recent literature related to the subject has been reviewed. The text has been divided into three main sections, addressing the effects of physical exercise during childhood/ adolescence, adulthood and aging, respectively. For each one, the most relevant studies, carried out on both human participants and rodent models, have been described. RESULTS: The data reviewed converge in indicating that physical activity exerts a positive effect on brain functioning throughout the lifespan. However, uncertainty remains about the magnitude of the effect and its biological underpinnings. Cellular and synaptic plasticity provided by adult neurogenesis are highly probable mediators, but the mechanism for their action has yet to be conclusively established. CONCLUSION: Despite alternative mechanisms of action are currently debated, age-appropriate physical activity programs may constitute a large-scale, relatively inexpensive and powerful approach to dampen the individual and social impact of age-related cognitive decline. PMID- 27000781 TI - Animal timing: a synthetic approach. AB - Inspired by Spence's seminal work on transposition, we propose a synthetic approach to understanding the temporal control of operant behavior. The approach takes as primitives the temporal generalization gradients obtained in prototypical concurrent and retrospective timing tasks and then combines them to synthetize more complex temporal performances. The approach is instantiated by the learning-to-time (LeT) model. The article is divided into three parts. In the first part, we review the basic findings concerning the generalization gradients observed in fixed-interval schedules, the peak procedure, and the temporal generalization procedure and then describe how LeT explains them. In the second part, we use LeT to derive by gradient combination the typical performances observed in mixed fixed-interval schedules, the free-operant psychophysical procedure, the temporal bisection task, and the double temporal bisection task. We also show how the model plays the role of a useful null hypothesis to examine whether temporal control in the bisection task is relative or absolute. In the third part, we identify a set of issues that must be solved to advance our understanding of temporal control, including the shape of the generalization gradients outside the range of trained stimulus durations, the nature of temporal memories, the influence of context on temporal learning, whether temporal control can be inhibitory, and whether temporal control is also relational. These issues attest to the heuristic value of a Spencean approach to temporal control. PMID- 27000780 TI - Critical issues in experimental studies of prosociality in non-human species. AB - Prosociality and acts of altruism are defined as behaviours which benefit another with either no gain or some immediate cost to the self. To understand the evolutionary origins of these behaviours, in recent years, studies have extended to primate species; however, studies on non-primates are still scarce. In light of the fact that phylogenetic closeness to humans does not appear to correlate with prosocial tendencies, but rather differences in the propensity towards prosociality may be linked to allomaternal care or collaborative foraging, it appears that convergent selection pressures may be at work in the evolution of prosociality. It would hence seem particularly important to extend such studies to species outside the primate clade, to allow for comparative hypothesis testing of the factors affecting the evolution of prosocial behaviours. In the current review, we focus on the experimental paradigms which have been used so far (i.e. the prosocial choice task, helping paradigms and food-sharing tests) and highlight the strengths and weaknesses of each method. In line with the aim of encouraging a broader comparative approach to the topic of prosociality, particular emphasis is placed on the methodological issues that need to be taken into account. We conclude that although a number of the paradigms used so far may be successfully applied to non-primate species, there is a need to simplify the cognitive demands of the tasks and ensure task comprehension to allow for a 'fair' comparative approach of prosocial tendencies across species. PMID- 27000782 TI - Comparative analysis of premature mortality among urban immigrants in Bremen, Germany: a retrospective register-based linkage study. AB - OBJECTIVES: The main objective of this study was to explore differences in mortality patterns among two large immigrant groups in Germany: one from Turkey and the other from the former Soviet Union (FSU). To this end, we investigated indicators of premature mortality. DESIGN: This study was conducted as a retrospective population-based study based on mortality register linkage. Using mortality data for the period 2004-2010, we calculated age-standardised death rates (SDR) and standardised mortality ratios (SMR) for premature deaths (20%). For each outcome, a set of logistic regression models were run. Crude and adjusted ORs were estimated for person-level deprivation, age, gender and smoking status. We included practice-level deprivation as a continuous variable and practice as a random effect to account for clustering. RESULTS: People who had lower Indices of Multiple Deprivation (IMD) scores (less deprived) had significantly worse routine CVD risk factor recording (adjusted OR 0.97 (0.95 to 1.00) per IMD decile; p=0.042). Screening attendance was poorer in those with more deprivation (adjusted OR 0.89 (0.86 to 0.91) per IMD decile; p<0.001). Among those who attended screening, the most deprived were more likely to have CVD risk >20% (OR 1.09 (1.03 to 1.15) per IMD decile; p=0.004). CONCLUSIONS: Our data suggest that those who had the most to gain from screening were least likely to attend, potentially exacerbating existing health inequalities. Future research should focus on tailoring the delivery of CVD screening to ensure engagement of socioeconomically deprived groups. PMID- 27000784 TI - Women's knowledge and attitudes surrounding abortion in Zambia: a cross-sectional survey across three provinces. AB - OBJECTIVES: In Zambia, despite a relatively liberal legal framework, there remains a substantial burden of unsafe abortion. Many women do not use skilled providers in a well-equipped setting, even where these are available. The aim of this study was to describe women's knowledge of the law relating to abortion and attitudes towards abortion in Zambia. SETTING: Community-based survey in Central, Copperbelt and Lusaka provinces. PARTICIPANTS: 1484 women of reproductive age (15 44 years). PRIMARY AND SECONDARY OUTCOME MEASURES: Correct knowledge of the legal grounds for abortion, attitudes towards abortion services and the previous abortions of friends, family or other confidants. Descriptive statistics and multivariable logistic regression were used to analyse how knowledge and attitudes varied according to sociodemographic characteristics. RESULTS: Overall, just 16% (95% CI 11% to 21%) of women of reproductive age correctly identified the grounds for which abortion is legal. Only 40% (95% CI 32% to 45% of women of reproductive age knew that abortion was legally permitted in the extreme situation where the pregnancy threatens the life of the mother. Even in urban areas of Lusaka province, only 55% (95% CI 41% to 67%) of women knew that an abortion could legally take place to save the mother's life. Attitudes remain conservative. Women with correct knowledge of abortion law in Zambia tended to have more liberal attitudes towards abortion and access to safe abortion services. Neither correct knowledge of the law nor attitudes towards abortion were associated with knowing someone who previously had an induced abortion. CONCLUSIONS: Poor knowledge and conservative attitudes are important obstacles to accessing safe abortion services. Changing knowledge and attitudes can be challenging for policymakers and public health practitioners alike. Zambia could draw on its previous experience in dealing with its large HIV epidemic to learn cross-cutting lessons in effective mass communication on what is a difficult and sensitive issue. PMID- 27000785 TI - Cardiac rehabilitation referral and enrolment across an academic health sciences centre with eReferral and peer navigation: a randomised controlled pilot trial. AB - OBJECTIVES: To describe (1) cardiac rehabilitation (CR) referral across cardiac units in a tertiary centre with eReferral; (2) characteristics associated with CR referral and enrolment and (3) the effects of peer navigation (PN) on referral and enrolment. This pilot was a 2 parallel-arm, randomised, single-blind trial with allocation concealment. SETTING: 3 cardiac units (ie, interventional, general cardiology, and cardiac surgery) in 1 of 2 hospitals of a tertiary centre. PARTICIPANTS: CR-eligible adult cardiac inpatients were randomised to PN or usual care. 94 (54.7%) patients consented, of which 46 (48.9%) were randomised to PN. Outcomes were ascertained in 76 (80.9%) participants. INTERVENTION: The PN (1) visited participant at the bedside, (2) mailed a card to participant's home reminding about CR and (3) called participant 2 weeks postdischarge to discuss CR barriers. OUTCOME MEASURES: The primary outcome of enrolment was defined as participant attendance at a scheduled CR intake appointment (yes/no). The secondary outcome was referral. Blinded outcome assessment was conducted 12 weeks postdischarge, via CR chart extraction. RESULTS: Those who received care on the cardiac surgery unit (77.9%) were more likely to be referred than those treated on the general cardiology (61.1%) or interventional unit (33.3%; p=0.04). Patients who had cardiac surgery, hypertension and hyperlipidaemia were significantly more likely, and those with congenital heart disease, cancer and a previous cardiac diagnosis were less likely to be referred. Participants referred to a site closer to home (76.2% of those referred) were more likely to enrol than those not (23.7%, p<0.05). PN had no effect on referral (77.6%, p=0.45) or enrolment (46.0%, p=0.24). CONCLUSIONS: There is wide variability in CR referral, even within academic centres, and despite eReferral. Referral was quite high, and thus, PN did not improve CR utilisation. Results support triaging patients to the CR programme closest to their home. TRIAL REGISTRATION NUMBER: NCT02204449; Results. PMID- 27000786 TI - Current status of pregnancy-related maternal mortality in Japan: a report from the Maternal Death Exploratory Committee in Japan. AB - OBJECTIVE: To clarify the problems related to maternal deaths in Japan, including the diseases themselves, causes, treatments and the hospital or regional systems. DESIGN: Descriptive study. SETTING: Maternal death registration system established by the Japan Association of Obstetricians and Gynecologists (JAOG). PARTICIPANTS: Women who died during pregnancy or within a year after delivery, from 2010 to 2014, throughout Japan (N=213). MAIN OUTCOME MEASURES: The preventability and problems in each maternal death. RESULTS: Maternal deaths were frequently caused by obstetric haemorrhage (23%), brain disease (16%), amniotic fluid embolism (12%), cardiovascular disease (8%) and pulmonary disease (8%). The Committee considered that it was impossible to prevent death in 51% of the cases, whereas they considered prevention in 26%, 15% and 7% of the cases to be slightly, moderately and highly possible, respectively. It was difficult to prevent maternal deaths due to amniotic fluid embolism and brain disease. In contrast, half of the deaths due to obstetric haemorrhage were considered preventable, because the peak duration between the initial symptoms and initial cardiopulmonary arrest was 1-3 h. CONCLUSIONS: A range of measures, including individual education and the construction of good relationships among regional hospitals, should be established in the near future, to improve primary care for patients with maternal haemorrhage and to save the lives of mothers in Japan. PMID- 27000787 TI - Perceptions and impact of plain packaging of tobacco products in low and middle income countries, middle to upper income countries and low-income settings in high-income countries: a systematic review of the literature. AB - OBJECTIVE: To review the current literature around the potential impact, effectiveness and perceptions of plain packaging in low income settings. METHOD: A systematic review of the literature. DATA SOURCES: 9 databases (PubMed, Global Health, Social Policy and Practice, Applied Social Sciences Index and Abstracts (ASSIA), CINAHL, PsycINFO, British Library for Development Studies (BLDS), Global Health Library and Scopus) were searched. The terms used for searching combined terms for smoking and tobacco use with terms for plain packaging. STUDY SELECTION: Studies investigating the impact of plain packaging on the determinants of tobacco use, such as smoking behaviour, appeal, prominence, effectiveness of health warnings, response to plain packs, attitudes towards quitting or likelihood of smoking in low-income settings, were identified. Studies must have been published in English and be original research of any level of rigour. DATA EXTRACTION: Two independent reviewers assessed studies for inclusion and extracted data. DATA SYNTHESIS: The results were synthesised qualitatively, with themes grouped under four key headings: appeal and attractiveness; salience of health warnings and perceptions of harm; enjoyment and perceived taste ratings; and perceptions of the impact on tobacco usage behaviour. RESULTS: This review has identified four articles that met the inclusion criteria. Studies identified that tobacco products in plain packaging had less appeal than in branded packaging in low-income settings. CONCLUSIONS: This review indicates that plain packaging appears to be successful in reducing appeal of smoking and packets, and supports the call for plain packaging to be widely implemented in conjunction with other tobacco control policies. However, there are considerable gaps in the amount of research conducted outside high income countries. PMID- 27000788 TI - Quetiapine use in adults in the community: a population-based study in Alberta, Canada. AB - OBJECTIVE: The objective of this study was to evaluate trends in prescribing of the second-generation antipsychotic medication quetiapine to adults in the province of Alberta from 2008 to 2013 through examination of dispensed prescriptions, and diagnoses associated with users of quetiapine in 2013. METHODS: We analysed administrative data from Alberta Health; the Alberta Pharmaceutical Information Network (PIN) Dispenses health data set, the Practitioner Payments (Fee-For-Service claims) health data set and the Population Registry health data set. These data sets allowed us to identify discrete quetiapine recipients for each calendar year from 2008 to 2013. To evaluate diagnoses associated with users of quetiapine, we evaluated diagnostic codes used by physicians in billings claims in 2013. RESULTS: Quetiapine use increased over the 6-year time period studied. In 2008, there were 16,087 unique quetiapine recipients in Alberta (7.2 per 1000). By 2013, there were 35,314 unique quetiapine recipients (13.3 per 1000). Use by women was higher than men at all time points. Depression was most common diagnosis associated with quetiapine recipients, which was present in 56% of users of quetiapine. Other common diagnoses associated with quetiapine use included neurotic disorders, bipolar disorder and sleep disturbances. CONCLUSIONS: The current study of quetiapine use in the province of Alberta provides confirmatory data of the increasing use of quetiapine for the treatment of depression and anxiety disorders. Safe and rational prescribing practices must be encouraged in light of the modest advantages of quetiapine over no treatment as an adjunctive treatment of major depression, and the known harms of this medication. PMID- 27000789 TI - Acid-Labile Amphiphilic PEO-b-PPO-b-PEO Copolymers: Degradable Poloxamer Analogs. AB - Poly ((ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)) triblock copolymers commonly known as poloxamers or Pluronics constitute an important class of nonionic, biocompatible surfactants. Here, a method is reported to incorporate two acid-labile acetal moieties in the backbone of poloxamers to generate acid-cleavable nonionic surfactants. Poly(propylene oxide) is functionalized by means of an acetate-protected vinyl ether to introduce acetal units. Three cleavable PEO-PPO-PEO triblock copolymers (Mn,total = 6600, 8000, 9150 g.mol(-1) ; Mn,PEO = 2200, 3600, 4750 g.mol(-1) ) have been synthesized using anionic ring-opening polymerization. The amphiphilic copolymers exhibit narrow molecular weight distributions (D = 1.06-1.08). Surface tension measurements reveal surface-active behavior in aqueous solution comparable to established noncleavable poloxamers. Complete hydrolysis of the labile junctions after acidic treatment is verified by size exclusion chromatography. The block copolymers have been employed as surfactants in a miniemulsion polymerization to generate polystyrene (PS) nanoparticles with mean diameters of ~200 nm and narrow size distribution, as determined by dynamic light scattering and scanning electron microscopy. Acid-triggered precipitation facilitates removal of surfactant fragments from the nanoparticles, which simplifies purification and enables nanoparticle precipitation "on demand." PMID- 27000790 TI - Extended phylogenetic analysis of a new Israeli isolate of Brevicoryne brassicae virus (BrBV-IL) suggests taxonomic revision of the genus Iflavirus. AB - BACKGROUND: Brevicoryne brassicae virus (BrBV) is a positive-strand genomic RNA virus which is unassigned tentative member of the genus Iflavirus. BrBv was first identified and characterized in the late 90's in the cabbage aphid in the United Kingdom (UK) (J Gen Virol 88:2590-2595, 2007) and was fully sequenced, using random amplification of encapsidated RNA. No other reports have been published demonstrating detection of this virus outside the UK. FINDINGS: A new isolate of the cabbage aphid virus Brevicoryne brassicae virus was identified from Brevicoryne brassicae aphids growing on wild mustard plants (Sinapis arvensis) in northern Israel. The virus genome was partially assembled from purified siRNA using the Illumina MiSeq Sequencing System with limited success. Combining classical viral RNA purification and RT-PCR amplification followed by traditional Sanger sequencing enabled obtaining the complete genomic sequence. The Israeli strain of BrBV shared 95 % nucleotide sequence identity with the BrBV found in the United Kingdom. CONCLUSIONS: The detection of BrBV in Israel indicates a broader geographical distribution of the virus". PMID- 27000791 TI - Genetic toxicology at the crossroads-from qualitative hazard evaluation to quantitative risk assessment. AB - Applied genetic toxicology is undergoing a transition from qualitative hazard identification to quantitative dose-response analysis and risk assessment. To facilitate this change, the Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC) sponsored a workshop held in Lancaster, UK on July 10-11, 2014. The event included invited speakers from several institutions and the contents was divided into three themes-1: Point-of departure Metrics for Quantitative Dose-Response Analysis in Genetic Toxicology; 2: Measurement and Estimation of Exposures for Better Extrapolation to Humans and 3: The Use of Quantitative Approaches in Genetic Toxicology for human health risk assessment (HHRA). A host of pertinent issues were discussed relating to the use of in vitro and in vivo dose-response data, the development of methods for in vitro to in vivo extrapolation and approaches to use in vivo dose-response data to determine human exposure limits for regulatory evaluations and decision making. This Special Issue, which was inspired by the workshop, contains a series of papers that collectively address topics related to the aforementioned themes. The Issue includes contributions that collectively evaluate, describe and discuss in silico, in vitro, in vivo and statistical approaches that are facilitating the shift from qualitative hazard evaluation to quantitative risk assessment. The use and application of the benchmark dose approach was a central theme in many of the workshop presentations and discussions, and the Special Issue includes several contributions that outline novel applications for the analysis and interpretation of genetic toxicity data. Although the contents of the Special Issue constitutes an important step towards the adoption of quantitative methods for regulatory assessment of genetic toxicity, formal acceptance of quantitative methods for HHRA and regulatory decision-making will require consensus regarding the relationships between genetic damage and disease, and the concomitant ability to use genetic toxicity results per se. PMID- 27000792 TI - Genotoxicity assessment of peptide/protein-related biotherapeutics: points to consider before testing. AB - The ICH S6(R1) recommendations on safety evaluation of biotherapeutics have led to uncertainty in determining what would constitute a cause for concern that would require genotoxicity testing. A Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee Workgroup was formed to review the current practice of genotoxicity assessment of peptide/protein-related biotherapeutics. There are a number of properties of peptide/protein-related biotherapeutics that distinguish such products from traditional 'small molecule' drugs and need to be taken into consideration when assessing whether genotoxicity testing may be warranted and if so, how to do it appropriately. Case examples were provided by participating companies and decision trees were elaborated to determine whether and when genotoxicity evaluation is needed for peptides containing natural amino acids, non-natural amino acids and other chemical entities and for unconjugated and conjugated proteins. From a scientific point of view, there is no reason for testing peptides containing exclusively natural amino acids irrespective of the manufacturing process. If non-natural amino acids, organic linkers and other non-linker chemical components have already been tested for genotoxicity, there is no need to re-evaluate them when used in different peptide/protein-related biotherapeutics. Unless the peptides have been modified to be able to enter the cells, it is generally more appropriate to evaluate the peptides containing the non-natural amino acids and other non-linker chemical moieties in vivo where the cleavage products can be formed. For linkers, it is important to determine if exposure to reactive forms are likely to occur and from which origin. When the linkers are anticipated to be potential mutagenic impurities they should be evaluated according to ICH M7. If linkers are expected to be catabolic products, it is recommended to test the entire conjugate in vivo, as this would ensure that the relevant 'free' linker forms stemming from in vivo catabolism are tested. PMID- 27000793 TI - Difficult-to-treat asthma and dysphagia in an adult patient with aberrant right subclavian artery. PMID- 27000795 TI - A cross-sectional study of parental awareness of and reasons for lack of health insurance among minority children, and the impact on health, access to care, and unmet needs. AB - BACKGROUND: Minority children have the highest US uninsurance rates; Latino and African-American children account for 53 % of uninsured American children, despite comprising only 48 % of the total US child population. The study aim was to examine parental awareness of and the reasons for lacking health insurance in Medicaid/CHIP-eligible minority children, and the impact of the children's uninsurance on health, access to care, unmet needs, and family financial burden. METHODS: For this cross-sectional study, a consecutive series of uninsured, Medicaid/CHIP-eligible Latino and African-American children was recruited at 97 urban Texas community sites, including supermarkets, health fairs, and schools. Measures/outcomes were assessed using validated instruments, and included sociodemographic characteristics, uninsurance duration, reasons for the child being uninsured, health status, special healthcare needs, access to medical and dental care, unmet needs, use of health services, quality of care, satisfaction with care, out-of-pocket costs of care, and financial burden. RESULTS: The mean time uninsured for the 267 participants was 14 months; 5 % had never been insured. The most common reason for insurance loss was expired and never reapplied (30 %), and for never being insured, high insurance costs. Only 49 % of parents were aware that their uninsured child was Medicaid/CHIP eligible. Thirty eight percent of children had suboptimal health, and 2/3 had special healthcare needs, but 64 % have no primary-care provider; 83 % of parents worry about their child's health more than others. Unmet healthcare needs include: healthcare, 73 %; mental healthcare, 70 %; mobility aids/devices, 67 %; dental, 61 %; specialty care, 57 %; and vision, 46 %. Due to the child's health, 35 % of parents had financial problems, 23 % cut work hours, and 10 % ceased work. Higher proportions of Latinos lack primary-care providers, and higher proportions of African Americans experience family financial burden. CONCLUSIONS: Half of parents of uninsured minority children are unaware that their children are Medicaid/CHIP eligible. These uninsured children have suboptimal health, impaired access to care, and major unmet needs. The child's health causes considerable family financial burden, and one in 10 parents ceased work. The study findings indicate urgent needs for better parental education about Medicaid/CHIP, and for improved Medicaid/CHIP outreach and enrollment. PMID- 27000796 TI - Health figures: an open source JavaScript library for health data visualization. AB - BACKGROUND: The way we look at data has a great impact on how we can understand it, particularly when the data is related to health and wellness. Due to the increased use of self-tracking devices and the ongoing shift towards preventive medicine, better understanding of our health data is an important part of improving the general welfare of the citizens. Electronic Health Records, self tracking devices and mobile applications provide a rich variety of data but it often becomes difficult to understand. We implemented the hFigures library inspired on the hGraph visualization with additional improvements. The purpose of the library is to provide a visual representation of the evolution of health measurements in a complete and useful manner. RESULTS: We researched the usefulness and usability of the library by building an application for health data visualization in a health coaching program. We performed a user evaluation with Heuristic Evaluation, Controlled User Testing and Usability Questionnaires. In the Heuristics Evaluation the average response was 6.3 out of 7 points and the Cognitive Walkthrough done by usability experts indicated no design or mismatch errors. In the CSUQ usability test the system obtained an average score of 6.13 out of 7, and in the ASQ usability test the overall satisfaction score was 6.64 out of 7. CONCLUSIONS: We developed hFigures, an open source library for visualizing a complete, accurate and normalized graphical representation of health data. The idea is based on the concept of the hGraph but it provides additional key features, including a comparison of multiple health measurements over time. We conducted a usability evaluation of the library as a key component of an application for health and wellness monitoring. The results indicate that the data visualization library was helpful in assisting users in understanding health data and its evolution over time. PMID- 27000794 TI - Urinary proteomics and metabolomics studies to monitor bladder health and urological diseases. AB - BACKGROUND: Assays of molecular biomarkers in urine are non-invasive compared to other body fluids and can be easily repeated. Based on the hypothesis that the secreted markers from the diseased organs may locally release into the body fluid in the vicinity of the injury, urine-based assays have been considered beneficial to monitoring bladder health and urological diseases. The urine proteome is much less complex than the serum and tissues, but nevertheless can contain biomarkers for diagnosis and prognosis of diseases. The urine metabolome has a much higher number and concentration of low-molecular metabolites than the serum or tissues, with a far lower lipid concentration, yet informs directly about dietary and microbial metabolism. DISCUSSION: We here discuss the use of mass spectrometry based proteomics and metabolomics for urine biomarker assays, specifically with respect to the underlying mechanisms that trigger the pathological condition. CONCLUSION: Molecular biomarker profiles, based on proteomics and metabolomics studies, reliably distinguish patients from healthy controls, stratify sub populations with respect to treatment options, and predict therapeutic response of patients with urological disease. PMID- 27000797 TI - Brain functional connectivity and cognition in mild traumatic brain injury. AB - INTRODUCTION: The aim of this study was to analyze brain functional connectivity and its relationship to cognition in patients with mild traumatic brain injury (mTBI). METHODS: Twenty-five patients with mTBI and 25 healthy control subjects were studied using resting-state functional MRI (rs-fMRI). Amplitudes of low frequency fluctuations (ALFFs) and functional connectivity (FC) were calculated and correlated with cognition. RESULTS: Compared with the normal control group, the mTBI patients showed a significant decrease in working memory index (WMI) and processing speed index (PSI), as well as significantly decreased ALFFs in the cingulate gyrus, the middle frontal gyrus and superior frontal gyrus. In contrast, the mTBI patients' ALFFs in the left middle occipital gyrus, the left precuneus, and lingual gyrus increased. Additionally, FC significantly decreased in the thalamus, caudate nucleus, and right hippocampus in the mTBI patients. Statistical analysis further showed a significant positive correlation between the ALFF in the cingulate gyrus and the WMI (R (2) = 0.423, P < 0.05) and a significant positive correlation between the FC in the left thalamus and left middle frontal gyrus and the WMI (R (2) = 0.381, P < 0.05). CONCLUSION: rs-fMRI can reveal the functional state of the brain in patients with mTBI. This finding differed from observations of the normal control group and was significantly associated with clinical cognitive dysfunction. Therefore, rs-fMRI offers an objective imaging modality for treatment planning and prognosis assessment in patients with mTBI. PMID- 27000798 TI - Erratum to: Induction of the Matrix Metalloproteinase 13 Gene in Bronchial Epithelial Cells by Interferon and Identification of its Novel Functional Polymorphism. PMID- 27000799 TI - Self-Treated Hypoglycemia in Type 2 Diabetes Mellitus: Results from the Second Wave of an International Cross-Sectional Survey. AB - INTRODUCTION: The aim of this study was to assess the total frequency of self treated hypoglycemia in type 2 diabetes mellitus patients using regimens including basal insulin analogs, and to describe the psychological impact and behavioral response to these events from the perspective of patients and prescribers (i.e., hospital specialists and primary care physicians). METHODS: The global attitude of patients and physicians 2 (GAPP2) survey was an online multinational, cross-sectional survey of patients with type 2 diabetes mellitus treated with basal insulin analogs, with or without bolus insulin. Prescribers directly involved in the care of these patients were also surveyed. Here, we report the results of the second wave of the GAPP2 survey, in which the primary variable of interest was self-treated hypoglycemia. RESULTS: A total of 855 patients and 1003 prescribers, from 7 countries, completed the survey. Overall, 28% of patients had experienced self-treated hypoglycemia during the previous 30 days, with two-thirds of events occurring during the day and one-third of events occurring nocturnally. Prescribers reported discussing events with 55% of patients over this period. Patients worried about self-treated hypoglycemia in a range of situations, and prescribers under-estimated this worry. Many patients who had experienced self-treated hypoglycemia in the last 30 days reported missing (19%), mistiming (7%), or reducing (7%) their basal insulin dose as a result. CONCLUSION: Self-treated hypoglycemia was relatively common in patients using basal insulin analogs, with or without bolus insulin. Whilst the frequency of hypoglycemia was greater during the daytime than at night, patients worried more about nocturnal events and this level of worry was under-estimated by physicians. Additional advice and support may be needed for both patients and prescribers, to reduce the frequency and impact of self-treated hypoglycemia. FUNDING: Novo Nordisk. PMID- 27000800 TI - Ethical and Practical Considerations in Removing Black Box Warnings from Drug Labels. AB - Boxed warnings-also known as "black box" warnings-can be a powerful tool in communicating drug risks to physicians and patients. The overall number of boxed warnings has grown in recent years as the US Food and Drug Administration (FDA) has approved more drugs on the basis of limited pre-marketing information and as new safety issues for marketed drugs have been identified. Two recent manufacturers' petitions to remove boxed warnings on the drugs rosiglitazone (Avandia) and varenicline (Chantix) have led to divergent FDA decisions and revealed different considerations involved in boxed warning imposition and removal. For ethical and practical reasons, the FDA is justified in applying a higher standard for boxed warning removal than for imposition, as removal of a boxed warning may have unintended effects on physician and patient behavior. However, no guidelines on boxed warning removal currently exist. To promote safe use of approved prescription drugs, the FDA should adopt a uniform and transparent process governing decisions to impose or remove boxed warnings. PMID- 27000801 TI - Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs. AB - Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and N(G)-nitro-L-arginine). Calcium influx studies in bronchopulmonary vagal afferent neurons dissociated from vagal sensory ganglia indicated that the tachykinin-containing C-fibers arising from the jugular ganglia mediate bradykinin-evoked coughing. Also implicating the jugular C-fibers was the observation that simultaneous blockade of neurokinin2 (NK2; SR48968) and NK3 (SR142801 or SB223412) receptors nearly abolished the bradykinin-evoked cough responses. The data suggest that bradykinin induces coughing in guinea pigs by activating B2 receptors on bronchopulmonary C-fibers. We speculate that therapeutics targeting the actions of bradykinin may prove useful in the treatment of cough. PMID- 27000802 TI - Metabolism of Anandamide by Human Cytochrome P450 2J2 in the Reconstituted System and Human Intestinal Microsomes. AB - According to the Centers for Disease Control and Prevention, the incidence of inflammatory bowel diseases (IBD) is about 1 in 250 people in the United States. The disease is characterized by chronic or recurring inflammation of the gut. Because of the localization of the endocannabinoid system in the gastrointestinal tract, it may be a potential pharmacologic target for the treatment of IBD and other diseases. Fatty acid amide hydrolase (FAAH) is a potential candidate because it is upregulated in IBD. FAAH hydrolyzes and, as a consequence, inactivates anandamide (AEA), a prominent endocannabinoid. Inhibition of FAAH would lead to increases in the amount of AEA oxidized by cytochrome P450s (P450s). CYP2J2, the major P450 epoxygenase expressed in the heart, is also expressed in the intestine and has previously been reported to oxidize AEA. We have investigated the possibility that it may play a role in AEA metabolism in the gut and have demonstrated that purified human CYP2J2 metabolizes AEA to form the 20-hydroxyeicosatetraenoic acid ethanolamide (HETE-EA) and several epoxygenated products, including the 5,6-, 8,9-, 11,12-, and 14,15 epoxyeicosatrienoic acid ethanolamides (EET-EAs), in the reconstituted system. Kinetic studies suggest that the KM values for these products range from approximately 10 to 468 MUM and the kcat values from 0.2 to 23.3 pmol/min per picomole of P450. Human intestinal microsomes, which express CYP2J2, metabolize AEA to give the 5,6-, 8,9-, and 11,12-EET-EAs, as well as 20-HETE-EA. Studies using specific P450 inhibitors suggest that although CYP2J2 metabolizes AEA, it is not the primary P450 responsible for AEA metabolism in human intestines. PMID- 27000803 TI - Phylogenomics of a rapid radiation: is chromosomal evolution linked to increased diversification in north american spiny lizards (Genus Sceloporus)? AB - BACKGROUND: Resolving the short phylogenetic branches that result from rapid evolutionary diversification often requires large numbers of loci. We collected targeted sequence capture data from 585 nuclear loci (541 ultraconserved elements and 44 protein-coding genes) to estimate the phylogenetic relationships among iguanian lizards in the North American genus Sceloporus. We tested for diversification rate shifts to determine if rapid radiation in the genus is correlated with chromosomal evolution. RESULTS: The phylogenomic trees that we obtained for Sceloporus using concatenation and coalescent-based species tree inference provide strong support for the monophyly and interrelationships among nearly all major groups. The diversification analysis supported one rate shift on the Sceloporus phylogeny approximately 20-25 million years ago that is associated with the doubling of the speciation rate from 0.06 species/million years (Ma) to 0.15 species/Ma. The posterior probability for this rate shift occurring on the branch leading to the Sceloporus species groups exhibiting increased chromosomal diversity is high (posterior probability = 0.997). CONCLUSIONS: Despite high levels of gene tree discordance, we were able to estimate a phylogenomic tree for Sceloporus that solves some of the taxonomic problems caused by previous analyses of fewer loci. The taxonomic changes that we propose using this new phylogenomic tree help clarify the number and composition of the major species groups in the genus. Our study provides new evidence for a putative link between chromosomal evolution and the rapid divergence and radiation of Sceloporus across North America. PMID- 27000804 TI - Newly discovered population of Aedes japonicus japonicus (Diptera: Culicidae) in Upper Bavaria, Germany, and Salzburg, Austria, is closely related to the Austrian/Slovenian bush mosquito population. AB - BACKGROUND: The German mosquito surveillance instrument 'Mueckenatlas' requests the general public to collect and submit mosquito specimens. Among these, increasing numbers of individuals of invasive species have been registered. Specimens of the Asian bush mosquito Aedes japonicus japonicus submitted from German Upper Bavaria, where this species had not previously been recorded, triggered regional monitoring in mid-2015. METHODS: The search for Ae. j. japonicus breeding sites and developmental stages concentrated on cemeteries in the municipality of origin of the submitted specimens and, subsequently, in the whole region. A virtual grid consisting of 10 * 10 km(2) cells in which up to three cemeteries were checked, was laid over the region. A cell was considered positive as soon as Ae. j. japonicus larvae were detected, and regarded negative when no larvae could be found in any of the cemeteries inspected. All cells surrounding a positive cell were screened accordingly. A subset of collected Aedes j. japonicus specimens was subjected to microsatellite and nad4 sequence analyses, and obtained data were compared to individuals from previously discovered European populations. RESULTS: Based on the grid cells, an area of approximately 900 km(2) was populated by Ae. j. japonicus in Upper Bavaria and neighbouring Austria. Genetic analyses of microsatellites and nad4 gene sequences generated one genotype out of two previously described for Europe and three haplotypes, one of which had previously been found in Europe only in Ae. j. japonicus samples from a population in East Austria and Slovenia. The genetic analysis suggests the new population is closely related to the Austrian/Slovenian population. CONCLUSION: As Ae. j. japonicus is well adapted to temperate climates, it has a strong tendency to expand and to colonise new territories in Central Europe, which is facilitated by human-mediated, passive transportation. The new population in Upper Bavaria/Austria is the seventh separate population described in Europe. According to our data, it originated from a previously detected population in eastern Austria/Slovenia and not from an introduction event from abroad. The dispersal and population dynamics of Ae. j. japonicus should be thoroughly surveyed, as this species is a potential vector of disease agents. PMID- 27000805 TI - Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. AB - Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) with electron transfer flavoprotein dehydrogenase (ETFDH) gene mutations is the most common lipid storage myopathy (LSM) in China. Its clinical features vary widely and pose a challenge for diagnosis. We presented the significant clinical heterogeneity among three Chinese late-onset MADD patients with similar ETFDH genotype by collecting clinical information, muscle histology, and genetic analysis. Three novel compound heterozygous variants of ETFDH gene were identified: c.892C > T (p.Pro298Ser), c.453delA (p.Glu152ArgfsTer15), and c.449_453delTAACA (p.Leu150Ter). Moreover, all patients carried a hotspot mutation c.250G > A (p.Ala84Thr). Western blot analysis of the patients' muscular tissue showed a significantly reduced ETFDH expression, and normal electron transfer flavoprotein A (ETFA) and electron transfer flavoprotein B (ETFB) expression. Two patients with similar genotypes (c.453delA and c.449_453delTAACA) presented a significant clinical heterogeneity. Among them, one exhibited muscle weakness and exercise intolerance as initial and major symptoms, and the other showed episodic recurrent gastrointestinal symptoms before a serious muscle weakness appeared in later life. The novel variants in ETFDH and the corresponding clinical features enrich the variant spectrum of late-onset MADD and provide a new insight into the genotype-phenotype relationship. Late-onset MADD should be included in differential diagnosis for adult myopathy along with chronic digestive disease. PMID- 27000806 TI - Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics. AB - BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer's protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. PMID- 27000807 TI - Native-Language Phonological Interference in Early Hakka-Mandarin Bilinguals' Visual Recognition of Chinese Two-Character Compounds: Evidence from the Semantic Relatedness Decision Task. AB - Previous research has indicated that, in viewing a visual word, the activated phonological representation in turn activates its homophone, causing semantic interference. Using this mechanism of phonological mediation, this study investigated native-language phonological interference in visual recognition of Chinese two-character compounds by early Hakka-Mandarin bilinguals. A visual semantic-relatedness decision task in Chinese was given to native Mandarin speakers and early Hakka-Mandarin bilinguals. Both participant groups made more false positive errors and responded more slowly to the pair of two-character compounds containing a homophone; but only Hakka-Mandarin bilinguals made more false positive errors and responded more slowly to the pair containing a near homophone. We concluded that phonology is needed in both native and nonnative speakers' meaning access of Chinese two-character compounds and that native language phonological interference is universal in L2 visual word recognition, not language type dependent; phonological and orthographic information are "interactive-compensatory" in helping Hakka readers' resolve the interference. PMID- 27000808 TI - Morphology and Spelling in Arabic: Development and Interface. AB - In the current study, two experiments were carried out: the first tested the development of derivational root and word-pattern morphological awareness in Arabic; the second tested morphological processing in Arabic spelling. 143 Arabic native speaking children with normal reading skills in 2nd, 4th and 6th grade participated in the study. The results of the first experiment demonstrated the early emergence of derivational morphological awareness in children, with root awareness emerging earlier than word-pattern awareness. The second experiment supported the implication of morphological processing in spelling words and pseudo words across all grades tested. The results are discussed within a developmental psycholinguistic framework with particular emphasis on the characteristics of the Arabic language and orthography. PMID- 27000809 TI - [Tooth erosion - a multidisciplinary approach]. AB - During the last decades, an increasingly greater interest in dental erosion has been observed in clinical dental practice, in dental public health and in dental research because prevalence of erosive tooth wear is still increasing especially in young age group of population. Erosive tooth wear is a multifactorial etiology process characterized by progressive loss of hard dental tissue. It is defined as the exogenous and/or endogenous acids dissolution of the dental tissue, without bacterial involvement. In the development of dental erosive wear, interactions are required which include chemical, biological, behavioral, diet, time, socioeconomic, knowledge, education, and general health factors. Examples of risk groups could be patients with eating disorders, like anorexia nervosa or bulimia nervosa, gastroesophageal reflux disease, chronic alcohol abuse or dependence. Special nutrition habits groups with high consumption of soft or sport drinks, special diets like vegetarian, vegan or raw food diet, the regular intake of drugs, medications and food supplements can also increase the risk for dental erosion. Comprehensive knowledge of the different risk and protective factors is a perquisite for initiating adequate preventive measures. PMID- 27000810 TI - [The prognostic value of basic laboratory blood tests in predicting the results of cardiac rehabilitation in post STEMI patients]. AB - The possibility of complications and death from cardiovascular causes in patients with acute coronary syndromes (ACS) is an important element in the assessment of their clinical condition. It is believed that the prognosis of patients after ACS is affected, among others, by leukocytosis, anemia, hyperglycemia, thrombocytopenia, and increased volume of these cells and decreased GFR. AIM: The aim of the study was an attempt to use basic laboratory blood tests and an index of own design to predict the results of in-hospital cardiac rehabilitation (phase II) of post STEMI patients. MATERIALS AND METHODS: The study included 100 post STEMI patients, 70 men and 30 women, aged 60,9+/-11,8 years, admitted for cardiac rehabilitation to the Department of Internal Diseases and Cardiac Rehabilitation, MU in Lodz. On admission fasting blood cell count was performed, serum glucose and creatinine level was determined (GFR assessment). The following results were considered abnormal: glucose level >=100mg/dl, GFR <60 ml/min/1,73m(2), RBC <4x10(6)/MUl, WBC >10x10(3)/MUl, PLT <150x10(3)/MUl. Exercise test was performed twice in all patients - before and after the completion of the II phase of rehabilitation to assess its effects. RESULTS: Basing on logistic regression analysis and the results of individual odds ratio (OR) of the tested blood parameters, their prognostic impact on the risk of cardiac rehabilitation failure was determined. This risk was defined on the basis of patient's inability to tolerate workload increment >=20 Watt despite the applied cardiac rehabilitation program. The most statistically significant risk factors were selected as the result of logistic regression model building on the basis of which cardiac rehabilitation failure index was determined. Leukocytosis and anemia determined most significantly the failure of cardiac rehabilitation (respectively: OR=6,4 and OR=2,9;p=0,01). They were used to construct a rehabilitation failure index with the values 0-2, as follows: 0 - corresponds to the situation of the absence of leukocytosis and anemia, 1 - corresponds to the situation of the occurrence of leucocytosis or anemia in post STEMI patients and was associated with 3,5-fold increase in the risk of not obtaining the full effect of cardiac rehabilitation, 2 - corresponds to the situation of the simultaneous occurrence of both parameters (leukocytosis and anemia) and was associated with 12,25-fold increase in the risk of not obtaining full effect of cardiac rehabilitation. CONCLUSIONS: Peripheral blood cell count is essential in predicting cardiac rehabilitation effects. Leukocytosis and anemia determine to the greatest degree the failure of cardiac rehabilitation. Cardiac rehabilitation failure index may be useful in classifying post STEMI patients into an appropriate model of rehabilitation. PMID- 27000811 TI - [Acceptance of the disease in patients with lung cancer]. AB - Lung cancer is the most common malignancy in men and the second frequent in women. Cancer is not without consequences on the life and functioning of a patient. The process of adopting the disease is based on restoring the patient's psychological balance, reduction of the emotional discomfort and self-confidence. AIM: The aim of the study was to assess the acceptance of lung cancer in patients with this diagnosis. MATERIALS AND METHODS: The study included 73 patients treated at the Pulmonology Ward of Podkarpackie Center for Lung Diseases, Department of Clinical Oncology of Podkarpackie Oncology Centre in Rzeszow and at the Department of Chemotherapy, Radiotherapy and Oncological Surgery of Podkarpackie Oncological Center in Brzozow. Author's questionnaire and Acceptance of Illness Scale (AIS) were used in the study. RESULTS: At the time of diagnosis 60.27% of the subjects accepted the disease, while at the time of the study 90.41% reconciled with the cancer diagnosis. The average degree of acceptance was found in 56.16% of the subjects. The respondents up to 60 years of age were characterized by a higher level of acceptance than patients over 60. The effect of age on the degree of being needed was observed, where higher average value was found in people up to 60 (p <0.05). It was demonstrated that age (up to 60) and the time elapsed since the diagnosis (up to 6 months) is significantly associated with less dependence on the others (p <0.05). CONCLUSIONS: The time elapsed since the diagnosis led to the increased in the acceptance of the disease. The age up to 60 was characterized by higher level of acceptance and a higher degree of being needed. PMID- 27000812 TI - Non-sustained ventricular tachycardia during treatment of genotype 3 chronic hepatitis C - a case report. AB - More than 185 million people around the world have been infected with the hepatitis C virus (HCV), of whom 350 000 die each year. HCV is a now a curable disease, and advances in HCV therapy have resulted in steadily higher cure rates. Therapies based on PegINF are still treatment of choice. However PegINF can induce severe adverse events including cardiovascular disease. CASE REPORT: Here we report a 55 year old female patient with the severe hepatitis C and genotype 3 presented with recurring episodes of the loss of consciousness and palpitations in the course of therapy, combining interferon PegINF with ribavirin. During the diagnostics performed the occurrence of non-sustained ventricular. There were no other causes of arrhythmias, such as coronary heart disease or heart failure. It is considered that this is a result of treatment. Because of the confirmed viral clearance completed PegINF therapy at a lower dose, without further complications. CONCLUSIONS: The presented case of our patient illustrates very well the level of difficulty of the taken decisions, especially when treatment complications occurred, while also confirming the fairly assistive and supportive role of the non-invasive methods of cardiovascular diagnostics. PMID- 27000813 TI - [Myopericarditis in a 23-year-old male with herpes zoster]. AB - The varicella zoster virus (VZV) belongs to cardiotropic viruses, although the frequency of cardiac complications during VZV infection is low. Diagnosis of myocarditis or myopericarditis is rare during varicella - primary infection of VZV and sporadic in zoster - reactivation of latent VZV. Only few such cases have been described. The authors present a case of a 23-year-old male in whom clinical symptoms of myopericarditis developed a week after diagnosis of zoster that was localized in the left-upper part of the thorax. Retrosternal chest pain and fever were accompanied by ECG mimicking acute myocardial infarction. A dynamic pattern of troponin I release and slow normalization of ECG were observed. Serial echocardiography showed normal left ventricular function, transient changes in echogenicity of the interventricular septum and small pericardial effusion. In magnetic resonance imaging subepicardial and intramyocardial areas of late gadolinium enhancement were found. He was treated with intravenous acyclovir. No late sequels of the disease were observed. PMID- 27000814 TI - [Life-threatening hypophosphatemia in 74-year-old woman with recurrent pneumonia and progressive muscular atrophy]. AB - Although hypophosphatemia can be a serious threat to health and life, it is a problem rarely taken into consideration in the differential diagnosis in the current clinical practice. The aim of the study was to present the description of hypophosphatemia issues in the context of the threat they may pose to the health and life when undiagnosed. CASE REPORT: 74-year-old internal charged woman , with progressive destruction for a few years, recurrent pneumonia, and a compression fracture of the spine, was admitted to hospital because of fainting and general deterioration. In the course of the performed diagnostics primary hyperparathyroidism was diagnosed with pre-existing inadequate severe hypophosphatemia. Because the presented clinical picture, only partially tie in symptomatology of primary hiperparathyroidism, the diagnostic process was targeted to search for other causes of both hypophosphatemia and symptoms reported by the patient. Finally, in addition to PHPT ( primary hyperparathyroidism) also vitamin D deficiency and tuberculosis was found. The fact that the treatment of infectious disease led to the phosphatemia standardization , and thus to significant improvement of the overall demonstrates, shows the significant contribution of tuberculosis in the pathogenesis of phosphate deficiency in this case. RESULTS: Our case is an example of confirming the need for a thorough and multidirectional analysis of the clinical picture, which is a prerequisite for a correct diagnosis. PMID- 27000815 TI - [Klatskin tumor - a case report]. AB - Cholangiocarcinoma (CCA) is the second most frequent liver malignancy, responsible for 10-15% primary liver cancers. This tumor is difficult to diagnose and characterized by high mortality rate. Extrahepatic CCA is a specific type known as Klatskin tumor. A CASE REPORT: The patient was admitted to the Clinic of Internal Medicine and Gastroenterology with intrahepatic cholestasis. Imaging revealed Bismuth type IV hilum tumor. Due to rare occurrence of this malignancy the patient was directed to the tertiary center. During surgical exploration radical treatment was abandoned as a result of tumor's advanced stadium. Histology evaluation revealed infiltrating adenocarcinoma. ERCP and biliary duct stenting was performed. The patient was qualified for paliative chemotherapy according to gemcytabine+cisplatine protocol (d1, d15 every 28 days). Posttreatment follow-up revealed total remission of the tumor. PMID- 27000816 TI - [Neurologic appearence of Behcet disease in 14-year old boy treated with adalimumab with good result]. AB - Behcet disease is a multiorgan inflammatory vessel disorder of unknown etiology which only occasionally occurs in children. Here, we demonstrate a 14-year-old boy with Behcet disease diagnosed based on recurrent aphthous stomatitis, acneiform facial lesions, subpreputial erosions and extensive thrombosis involving sigmoid sinus, transverse sinus and right internal cervical vein. Treatment with low molecular weight heparins, systemic corticosteroids, and azathioprine only resulted in partial remission of clinical symptoms. Addition of adalimumab led to complete resolution of clinical and biochemical abnormalities and disappearance of thrombosis in central nervous system. PMID- 27000817 TI - [Hereditary pancreatitis]. AB - Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. with an early onset, mostly during childhood. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common are mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). The inflammation results in repeated DNA damage, error-prone repair mechanisms and the progressive accumulation of genetic mutations. Risk of pancreatic adenocarcinoma is a major concern of many patients with hereditary chronic pancreatitis, but the individual risk is poorly defined. Better risk models of pancreatic cancer in individual patients based on etiology of pancreatitis, family history, genetics, smoking, alcohol, diabetes and the patient's age are needed. PMID- 27000818 TI - [Clinical importance and diagnostic methods of minimal hepatic encephalopathy]. AB - Minimal hepatic encephalopathy (MHE) encompasses a number of neuropsychological and neurophysiological disorders in patients suffering from liver cirrhosis, who do not display abnormalities during a medical interview or physical examination. A negative influence of MHE on the quality of life of patients suffering from liver cirrhosis was confirmed, which include retardation of ability of operating motor vehicles and disruption of multiple health-related areas, as well as functioning in the society. The data on frequency of traffic offences and accidents amongst patients diagnosed with MHE in comparison to patients diagnosed with liver cirrhosis without MHE, as well as healthy persons is alarming. Those patients are unaware of their disorder and retardation of their ability to operate vehicles, therefore it is of utmost importance to define this group. The term minimal hepatic encephalopathy (formerly "subclinical" encephalopathy) erroneously suggested the unnecessity of diagnostic and therapeutic procedures in patients with liver cirrhosis. Diagnosing MHE is an important predictive factor for occurrence of overt encephalopathy - more than 50% of patients with this diagnosis develop overt encephalopathy during a period of 30 months after. Early diagnosing MHE gives a chance to implement proper treatment which can be a prevention of overt encephalopathy. Due to continuing lack of clinical research there exist no commonly agreed-upon standards for definition, diagnostics, classification and treatment of hepatic encephalopathy. This article introduces the newest findings regarding the importance of MHE, scientific recommendations and provides detailed descriptions of the most valuable diagnostic methods. PMID- 27000819 TI - [Adipose tissue, adipokines and aging]. AB - Adipokines are substances secreted by white adipose tissue of auto-, para- and endocrine functions. They play part mainly in maintaining energy balance. Aging influences the profile of secreted adipokines, what is caused probably by increasing visceral fat, intensified low grade systemic inflammation (LGSI) and the change in adipocyte size. In this article we focus on some selected adipokines (leptin, adiponectin, visfatin, vaspin, omentin, chemerin and retinol binding protein 4 - RBP4) paying special attention to the impact of aging on their blood concentrations and functions. Blood concentrations of leptin, vaspin, chemerin and RBP4 increase with age. It is associated with adverse lipid profile, insulin resistance and the increased risk of cardiovascular diseases, type 2 diabetes, malignancies and autoimmunity. It has been proved that long-lived people have more beneficial adipokines profile i.e. low leptin and especially high adiponectin concentrations what is additionally connected with higher concentration of HDL cholesterol, lower concentrations of HbA1C hemoglobin and C reactive protein, lower waist-to-hip ratio and fat mass. Moreoer, it seems that maintaining high adiponectin and omentin blood concentrations with low fat mass and preserved insulin sensitivity promote longevity. Furthermore, it has been proved that intensive exercises in old age lead to beneficial changes in adipokines profile, decrease in visceral fat, better insulin sensitivity and lipid profile. PMID- 27000820 TI - [Post-Lyme disease syndrome]. AB - Lyme disease is a chronic infectious disease caused by the bacteria, spirochete of the Borrelia type. Skin, nervous system, musculoskeletal system and heart may be involved in the course of the disease. The prognosis for properly treated Lyme disease is usually good. However, in about 5% of patients so called Post-Lyme disease syndrome (PLSD) develops. It is defined as a syndrome of subjective symptoms persisting despite proper treatment of Borrelia burgdorferi infection. The most common symptoms include: fatigue, muscle and joint pain, and problems with memory and concentration. Pathogenesis of PLDS remains unknown. The differential diagnosis should include neurological, rheumatic and mental diseases. Till now there is no causative treatment of PLDS. In relieving symptom rehabilitation, painkillers, anti-inflammatory and antidepressants medicines are recommended. Emotional and psychological supports are also necessary. Non specific symptoms reported by patients with post- Lyme disease syndrome raise the suspicion of other pathologies. This can lead to misdiagnosis and implementation of unnecessary, potentially harmful to the patient's therapy. An increase in tick borne diseases needs to increase physicians awareness of these issues. PMID- 27000821 TI - [The role of flavonoids in the modulation of inflammation]. AB - Chronic inflammation in the body leads to the formation and development many diseases, e.g. atherosclerosis, diabetes, neurodegenerative diseases or cancer and others. Therefore, the search for new and safe compounds of plant origin having antiinflammatory activity. They include, among others, naturally occurring in the diet of human - flavonoids. Anti-inflammatory effects of these compounds is due to their antioxidant properties, ability to inhibit enzymes involved in the metabolism of eicosanoids and proinflammatory molecules and modulate the expression of certain proinflammatory genes. Intensive studies in vitro and in vivo antiinflammatory activity of flavonoids are important not only because of the knowledge of the mechanisms of action of these compounds, but also to develop a new class of safe anti-inflammatory drugs of plant origin. This should bring prophylactic and therapeutic benefits. A diet rich in flavonoid compounds and/or supplementation with these compounds not only improve the efficiency of prevention of nutrition, but also complement the medical therapy of many diseases. PMID- 27000822 TI - [Treatment of generalized anxiety disorder in terms of cognitive behavioral]. AB - Risk of generalized anxiety disorder (GAD) within life is estimated at 2.6-5.1%. Amongst etiological factors that affect the development of the disorder are: biological and psychological problems, including cognitive models. There are known several cognitive models: metacognitive, Borkovec'c model and the model developed in Quebec. Key cognitive contents that occur with generalized anxiety disorder are focused on two aspects: metacognitive beliefs and intolerance of uncertainty. A primary purpose of cognitive-behavioural therapy (CBT) is the modification of dysfunctional beliefs about worry. Cognitive behavioural therapy is effective in reducing anxiety, makes it easier to operate in the professional sphere and improves the quality of life. PMID- 27000823 TI - Daily Deviations in Anger, Guilt, and Sympathy: A Developmental Diary Study of Aggression. AB - With a diary study of 4- and 8-year-olds, we tested the association between daily deviations in anger and aggressive behavior, and whether this link was moderated by feelings of guilt and sympathy. Caregivers reported their children's anger and aggression for 10 consecutive days (470 records; N = 80, 53 % girls). To calculate daily anger deviations from average anger levels, we subtracted each child's average anger score (i.e., across 10 days) from his/her daily anger scores. Children reported their guilty feelings in response to vignettes depicting intentional harm, as well as their dispositional sympathy levels. Multilevel modeling indicated that within-child spikes in daily anger were associated with more aggression, above and beyond between-child differences in average anger levels. However, this association was weaker for children who reported higher levels of guilt. Sympathy did not moderate the anger-aggression link. We discuss potential implications for affective-developmental models of aggression and interventions that target anger-related aggression. PMID- 27000825 TI - Phytochemicals as Prototypes for Pharmaceutical Leads Towards Drug Development Against Diabetic Cardiomyopathy. AB - Globally diabetes mellitus (DM) is swiftly reaching epidemic proportions and impose major health care and socio-economic challenges that are associated with its complications. DM is considered as the major risk factor for the development of debilitating micro & macro vascular complications. Clinical studies have revealed that development of diabetic cardiomyopathy (DCM) in subjects with diabetes can occur both- dependent and independent of pre-existing increased risk factors such as poor glycemic control, hyperlipidemia, and or hypertension. Therefore, DCM represents as a major challenge for the clinical community for the prompt diagnosis and devising the treatment paradigm to combat the diabetes induced cardiac dysfunction. In Chinese traditional medical practice, heart ailments have been coped with herbal extracts. Phytochemicals bioavailability and pharmacokinetic properties are to yet be established completely in human subjects. However, tremendous progress has been made to isolate, purify the phytochemicals and characterize their effects on mitigating the development of DCM in pre-clinical models. Currently there are no approved drugs available for the treatment of DCM. In this review, we have discussed the progress made in understanding the mechanisms for the phytochemicals cardio-protective actions in the diabetic milieu and their caveats and provide future perspectives for proposing these agents to serve as prototypes in the development of drugs for the management of DCM. PMID- 27000824 TI - Identification of allelic expression imbalance genes in human hepatocellular carcinoma through massively parallel DNA and RNA sequencing. AB - Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. The prognosis and treatment of this disease have changed little in recent decades because the mechanisms underlying most events of this disease remain obscure. Allelic variation of gene expression is associated with many important biological processes, which provide a new perspective to understand HCC pathogenesis at the molecular level. To identify allelic expression imbalance (AEI) genes in HCCs, we developed a computational method that considered accurate mapping and vigorous AEI detection using paired DNA-seq and RNA-seq data. We analyzed the DNA-seq and RNA-seq data derived from two HCC samples and two cell lines. By applying a strict criterion, a total of 203 tumor-specific AEI genes were identified with high confidence, and several genes have been reported to be associated with the migration or proliferation of cancer cells, such as the genes RELN and DHRS3. In addition, we also found some novel AEI genes in HCCs, such as HNRNPR and PTAFR. Our study provides new insight into AEI events that may contribute to understanding gene expression regulation, cell proliferation and migration, and tumorigenesis. PMID- 27000826 TI - The Immunomodulatory Effects of Physical Activity. AB - BACKGROUND: An individual's level of physical activity is one of a set of lifestyle and behavioral factors that can affect immune function and health. METHODS: The purpose of this review is to summarize the current knowledge in this research field and to review the recent developments in exercise immunology. RESULTS: Most studies show that regular exercise training increases immune competence and reduces the risk of infection compared to a sedentary lifestyle. In contrast, acute prolonged bouts of exercise and periods of intensified training are followed by a temporary increase in the risk of infection. These observations have been attributed to differential exercise-induced changes of a series of humoral and cellular immune system parameters. Furthermore, regular exercise training is a countermeasure against a persistent systemic inflammatory state which is a typical feature of cardiovascular and metabolic diseases is by lowering levels of pro-inflammatory cytokines. It is supposed that these effects are mediated by a modification of metabolic signals and innate immune regulation, the release of anti-inflammatory cytokines from muscle, the release of stress hormones, and a process known as browning of adipose tissue. CONCLUSION: The effects of physical activity on the immune system strongly depend on the mode and intensity of exercise or training. Thereby, considerable knowledge has accumulated concerning the significance of exercise as an important lifestyle factor for prevention and therapy of major chronic diseases. PMID- 27000827 TI - Intra-Renal Hemodynamic Changes After Habitual Physical Activity in Patients with Chronic Kidney Disease. AB - BACKGROUND: Chronic Kidney Disease (CKD) is considered a silent epidemic with a continuously growing prevalence around the world. Due to uremia many functional and morphological abnormalities occur in almost all systems. Mostly affected, the cardiovascular system, leads to diminished cardiac function that affects patients' functional capacity and physical activity levels, reducing survival and increasing all-cause mortality. Systematic exercise training ameliorates uremia induced body deficits and significantly improves the survival of CKD patients. Intradialytic exercise training has been recommended as a complementary therapeutic modality equally important to hemodialysis. METHODS: The aim of this systematic review is to provide an update on recent advances in our understanding of how exercise training improves functionality of the cardiovascular system through the hemodynamic changes induced by habitual or intradialytic and/or home based exercise training programs. RESULTS: Systematic exercise training induces beneficial adaptive responses and influences many sensitive physiological biomarkers, such as oxidative stress biomarkers that are implicated in the development of atherosclerosis. Additionally, exercise training decreases the cardiovascular risk by improving the autonomic nervous system activity and the left ventricular function and by reducing nontraditional risk factors such as epicardial adipose tissue. It seems that all these central and peripheral adaptations to exercise training significantly contribute to improvements in functional capacity and exercise tolerance among CKD patients and result in the risk reduction of CKD-associated disorders. CONCLUSION: Exercise training could serve as a complimentary therapeutic strategy in CKD patients while health care providers should motivate patients to engage in any type of exercise training programs. PMID- 27000828 TI - Regular Physical Activity and Vascular Aging. AB - BACKGROUND: Aging and low physical activity are associated with the development of diseases (hypertension, type 2 diabetes, dyslipidemia, obesity) marked by chronic low-grade inflammation. Cardiovascular disease is the most common cause of death worldwide, while exercising muscle tissue can increase the secretion of myokines that can reestablish a possible inflammatory process in virtue of the anti-inflammatory effect. METHODS: The objective of this review is to focus on molecular mechanisms involved between different kinds of exercise and cellular oxidative stress, and the emerging therapeutic strategies which have the potential to promote benefits in vascular health. RESULTS: Regular exercise increases shear stress, mitochondrial biogenesis, and upregulates mitochondrial antioxidant system, inducing anti-inflammatory actions, such as suppression of TNF-alpha which may offer protection against TNF-alpha-induced vascular impairment. CONCLUSION: Exercise training of various durations and intensities appears to prevent and restore the age-related impairment of endothelial function, likely through the restoration of NO availability, reduction in oxidative stress, and turnover of the apoptotic process in the endothelium, thus minimizing vascular inflammation and decreasing the formation of atherosclerotic plaques. PMID- 27000829 TI - Biological Rationale for Regular Physical Exercise as an Effective Intervention for the Prevention and Treatment of Depressive Disorders. AB - Depression is a major medical and social problem. Here we review current body of knowledge on the benefits of exercise as an effective strategy for both the prevention and treatment of this condition. We also analyze the biological pathways involved in such potential benefits, which include changes in neurotrophic factors, oxidative stress and inflammation, telomere length, brain volume and microvessels, neurotransmitters or hormones. We also identify major caveats in this field of research: further studies are needed to identify which are the most appropriate types of exercise interventions (intensity, duration, or frequency) to treat and prevent depression. PMID- 27000830 TI - Water Quality Assessment of River Soan (Pakistan) and Source Apportionment of Pollution Sources Through Receptor Modeling. AB - The present study was designed to determine the spatiotemporal patterns in water quality of River Soan using multivariate statistics. A total of 26 sites were surveyed along River Soan and its associated tributaries during pre- and post monsoon seasons in 2008. Hierarchical agglomerative cluster analysis (HACA) classified sampling sites into three groups according to their degree of pollution, which ranged from least to high degradation of water quality. Discriminant function analysis (DFA) revealed that alkalinity, orthophosphates, nitrates, ammonia, salinity, and Cd were variables that significantly discriminate among three groups identified by HACA. Temporal trends as identified through DFA revealed that COD, DO, pH, Cu, Cd, and Cr could be attributed for major seasonal variations in water quality. PCA/FA identified six factors as potential sources of pollution of River Soan. Absolute principal component scores using multiple regression method (APCS-MLR) further explained the percent contribution from each source. Heavy metals were largely added through industrial activities (28 %) and sewage waste (28 %), nutrients through agriculture runoff (35 %) and sewage waste (28 %), organic pollution through sewage waste (27 %) and urban runoff (17 %) and macroelements through urban runoff (39 %), and mineralization and sewage waste (30 %). The present study showed that anthropogenic activities are the major source of variations in River Soan. In order to address the water quality issues, implementation of effective waste management measures are needed. PMID- 27000831 TI - New Insights into Enhancing Maximal Exercise Performance Through the Use of a Bitter Tastant. AB - It is generally acknowledged that for an orally administered ergogenic aid to enhance exercise performance it must first be absorbed by the gastrointestinal tract before exerting its effects. Recently, however, it has been reported that some ergogenic aids can affect exercise performance without prior absorption by the gastrointestinal tract. This is best illustrated by studies that have shown that rinsing the mouth with a carbohydrate (CHO) solution, without swallowing it, significantly improves exercise performance. The ergogenic effects of CHO mouth rinsing in these studies have been attributed to the activation of the brain by afferent taste signals, but the specific mechanisms by which this brain activation translates to enhanced exercise performance have not yet been elucidated. Given the benefits of CHO mouth rinsing for exercise performance, this raises the issue of whether other types of tastants, such as bitter-tasting solutions, may also improve exercise performance. Recently, we performed a series of studies investigating whether the bitter tastant quinine can improve maximal sprint performance in competitive male cyclists, and, if so, to examine some of the possible mechanisms whereby this effect may occur. These studies have shown that mouth rinsing and ingesting a bitter-tasting quinine solution can significantly improve the performance of a maximal cycling sprint. There is also evidence that the ergogenic effect of quinine is mediated, at least in part, by an increase in autonomic nervous system activation and/or corticomotor excitability. The purpose of this article is to discuss the results and implications of these recent studies and to suggest avenues for further research, which may add to the understanding of the way the brain integrates signals from the oral cavity with motor behaviour, as well as uncover novel strategies to improve exercise performance. PMID- 27000832 TI - In situ expansion of T cells that recognize distinct self-antigens sustains autoimmunity in the CNS. AB - Polyspecific T cells recognizing multiple distinct self-antigens have been identified in multiple sclerosis and other organ-specific autoimmune diseases, but their pathophysiological relevance remains undetermined. Using a mouse model of multiple sclerosis, we show that autoimmune encephalomyelitis induction is strictly dependent on reactivation of pathogenic T cells by a peptide (35-55) derived from myelin oligodendrocyte glycoprotein (MOG). This disease-inducing response wanes after onset. Strikingly, the progression of disease is driven by the in situ activation and expansion of a minority of MOG35-55-specific T cells that also recognize neurofilament-medium (NF-M)15-35, an intermediate filament protein expressed in neurons. This mobilization of bispecific T cells is critical for disease progression as adoptive transfer of NF-M15-35/MOG35-55 bispecific T cell lines caused full-blown disease in wild-type but not NF-M-deficient recipients. Moreover, specific tolerance through injection of NF-M15-35 peptide at the peak of disease halted experimental autoimmune encephalomyelitis progression. Our findings highlight the importance of polyspecific autoreactive T cells in the aggravation and perpetuation of central nervous system autoimmunity. PMID- 27000833 TI - Differential introgression and the maintenance of species boundaries in an advanced generation avian hybrid zone. AB - BACKGROUND: Evolutionary processes, including selection and differential fitness, shape the introgression of genetic material across a hybrid zone, resulting in the exchange of some genes but not others. Differential introgression of molecular or phenotypic markers can thus provide insight into factors contributing to reproductive isolation. We characterized patterns of genetic variation across a hybrid zone between two tidal marsh birds, Saltmarsh (Ammodramus caudacutus) and Nelson's (A. nelsoni) sparrows (n = 286), and compared patterns of introgression among multiple genetic markers and phenotypic traits. RESULTS: Geographic and genomic cline analyses revealed variable patterns of introgression among marker types. Most markers exhibited gradual clines and indicated that introgression exceeds the spatial extent of the previously documented hybrid zone. We found steeper clines, indicating strong selection for loci associated with traits related to tidal marsh adaptations, including for a marker linked to a gene region associated with metabolic functions, including an osmotic regulatory pathway, as well as for a marker related to melanin-based pigmentation, supporting an adaptive role of darker plumage (salt marsh melanism) in tidal marshes. Narrow clines at mitochondrial and sex-linked markers also offer support for Haldane's rule. We detected patterns of asymmetrical introgression toward A. caudacutus, which may be driven by differences in mating strategy or differences in population density between the two species. CONCLUSIONS: Our findings offer insight into the dynamics of a hybrid zone traversing a unique environmental gradient and provide evidence for a role of ecological divergence in the maintenance of pure species boundaries despite ongoing gene flow. PMID- 27000834 TI - Chicken IgY Fc expressed by Eimeria mitis enhances the immunogenicity of E. mitis. AB - BACKGROUND: Eimeria species are obligate intracellular apicomplexan parasites, causing great economic losses in the poultry industry. Currently wild-and attenuated- type anticoccidial vaccines are used to control coccidiosis. However, their use in fast growing broilers is limited by vaccination side effects caused by medium and/or low immunogenic Eimeria spp. There is, therefore, a need for a vaccine with high immunogenicity for broilers. METHODS: The avian yolk sac IgY Fc is the avian counterpart of the mammalian IgG Fc, which enhances immunogenicity of Fc-fusion proteins. Here, we developed a stable transgenic Eimeria mitis expressing IgY Fc (Emi.chFc) and investigated whether the avian IgY Fc fragment enhances the immunogenicity of E. mitis. Two-week-old broilers were immunized with either Emi.chFc or wild type Eimeria and challenged with wild type E. mitis to analyze the protective properties of transgenic Emi.chFc. RESULTS: Chickens immunized with Emi.chFc had significantly lower oocyst output, in comparison with PBS, mock control (transgenic E. mitis expressing HA1 from H9N2 avian influenza virus) and wildtype E. mitis immunized groups after challenge, indicating that IgY Fc enhanced the immunogenicity of E. mitis. CONCLUSIONS: Our findings suggest that IgY Fc-expressing Eimeria may be a better coccidiosis vaccine, and transgenic Eimeria expressing Fc-fused exogenous antigens may be used as a novel vaccine-delivery vehicle against a wide variety of pathogens. PMID- 27000835 TI - Learning from Somaliland? Transferability of learning from volunteering to national health service practice in the UK. AB - BACKGROUND: Capacity building partnerships between healthcare institutions have the potential to benefit both partners particularly in staff development. Previous research suggests that volunteering can contribute to professional development but there is little evidence on how learning is acquired, the barriers and facilitators to learning in this context or the process of translation of learning to the home environment. RESULTS: Volunteers from a healthcare partnership between the UK and Somaliland reported learning in communication, interdisciplinary working, teaching, management, leadership and service development. This learning came from observing familiar practices in unfamiliar environments; alternative solutions to familiar problems; learning about Somali culture; opportunities to assume higher levels of responsibility and new professional relationships. There was variability in the extent of translation to NHS practice. Time and support available for reflection and mentoring were important facilitators of this process. CONCLUSIONS: The professional development outcomes documented in this study came directly from the experience of volunteering. Experiential learning theory suggests that this requires a complex process of critical reflection and new knowledge generation, testing and translation for use in new contexts. This process benefits from identification of learning as an important element of volunteering and support for reflection and the translation translation of learning to UK contexts. We suggest that missed opportunities for volunteer learning will remain until the volunteering process is overtly framed as part of continuing professional development. PMID- 27000836 TI - Maternal Psychological Control and Its Association with Mother and Child Perceptions of Adolescent Adjustment: More Evidence on the Strength of Shared Perspectives. AB - Mothers and adolescents hold distinct albeit correlated views of their relationship and of one another. The present study focuses on disentangling these independent views. Concurrent associations between maternal psychological control and children's adjustment are examined at two time points in order to identify the degree to which associations reflect (a) views that are shared by mothers and adolescents, and (b) views that are unique to mothers and adolescents. A total of 123 (56 % female) U.S. Latino/a adolescents (M = 10.4 years old at the outset) and their mothers reported on maternal psychological control, children's conduct problems, and children's anxiety, twice within a 5-month period. Data were collected at the close of primary school when the adolescents were in grade 5 and again at the beginning of middle school, when they were in grade 6. Results from conventional correlations indicated that mother- and adolescent-reports yielded similar associations between maternal psychological control and adolescent adjustment. Common fate model analyses partitioned results into variance shared across mother and adolescent reports and variance unique to mother and adolescent reports. Results differed for anxiety and conduct problems. Shared views indicated that greater maternal psychological control was associated with heightened child conduct problems; there were no associations unique to either reporter. In contrast, unique reporter views indicated that greater maternal psychological control was associated with child anxiety; there were no associations involving shared views. Although mother- and adolescent-reports agree that maternal psychological control is correlated with children's adjustment, there is considerable divergence in results when associations are partitioned according to shared and unique reporter views. Associations between maternal psychological control and children's anxiety are more apt to be inflated by same-reporter variance bias than are associations between maternal psychological control and children's conduct problems. PMID- 27000837 TI - Targeted Downregulation of dMyc Suppresses Pathogenesis of Human Neuronal Tauopathies in Drosophila by Limiting Heterochromatin Relaxation and Tau Hyperphosphorylation. AB - Human tauopathies such as Alzheimer's Disease (AD), frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease etc., are a group of neurodegenerative diseases which are characterized by abnormal hyperphosphorylation of tau that leads to formation of neurofibrillary tangles. Recapitulating several features of human neurodegenerative disorders, the Drosophila tauopathy model displays compromised lifespan, locomotor function impairment, and brain vacuolization in adult brain which is progressive and age dependent. Here, we demonstrate that tissue-specific downregulation of the Drosophila homolog of human c-myc proto-oncogene (dMyc) suppresses tau-mediated morphological and functional deficits by reducing abnormal tau hyperphosphorylation and restoring the heterochromatin loss. Our studies show for the first time that the inherent chromatin remodeling ability of myc proto oncogenes could be exploited to limit the pathogenesis of human neuronal tauopathies in the Drosophila disease model. Interestingly, recent reports on successful uses of some anti-cancer drugs against Alzheimer's and Parkinson's diseases in clinical trials and animal models strongly support our findings and proposed possibility. PMID- 27000838 TI - Neuroprotective Activity of Grape Seed and Skin Extract Against Lithium Exposure Using Proteomic Research. AB - Lithium (Li) has raised scientific concern because it represents a serious problem threatening human health. This study aimed firstly at analyzing and potentially quantifying the impact of Li and grape seed and skin extract (GSSE) separately and, secondly, describing the possible neuroprotective activity of GSSE against Li toxicity. To this end, rats were exposed for 30 days to different Li concentrations (0, 2, and 100 mg/kg bw), to GSSE (4000 mg/kg bw), and to binary mixture of Li and GSSE. Liquid chromatography (HPLC-MS/MS) analysis used for GSSE showed that 15 phenolic compounds are present in the extract. Significant modifications of proteins were detected in the brain using proteomics research after treatment. Proteins were successfully identified by a linear ion trap-Orbitrap mass spectrometer. These proteins can be roughly related to oxidative stress, glycolysis, signaling pathway, and inflammation. Additionally, proteins involved in cell junction such as myosin, spectrin, tubulin, ERM-binding phosphoprotein, and dynein were also affected by Li exposure. Dose response was detected for most expressed proteins after Li treatment. In contrast, GSSE induced the expression and/or the stabilization of some proteins changed after Li treatment in the brain showing its neuroprotective activity. These data demonstrate that proteomic analysis is a powerful tool to provide valuable insights into mechanisms of toxicity of Li in the nervous system of Wistar rats. To our knowledge, this is the first evidence of using GSSE as neuroprotective model against Li toxicity. These findings provide impetus for future investigation on GSSE against other toxic chemicals. PMID- 27000839 TI - Characterization of a type I pullulanase from Anoxybacillus sp. SK3-4 reveals an unusual substrate hydrolysis. AB - Type I pullulanases are enzymes that specifically hydrolyse alpha-1,6 linkages in polysaccharides. This study reports the analyses of a novel type I pullulanase (PulASK) from Anoxybacillus sp. SK3-4. Purified PulASK (molecular mass of 80 kDa) was stable at pH 5.0-6.0 and was most active at pH 6.0. The optimum temperature for PulASK was 60 degrees C, and the enzyme was reasonably stable at this temperature. Pullulan was the preferred substrate for PulASK, with 89.90 % adsorbance efficiency (various other starches, 56.26-72.93 % efficiency). Similar to other type I pullulanases, maltotriose was formed on digestion of pullulan by PulASK. PulASK also reacted with beta-limit dextrin, a sugar rich in short branches, and formed maltotriose, maltotetraose and maltopentaose. Nevertheless, PulASK was found to preferably debranch long branches at alpha-1,6 glycosidic bonds of starch, producing amylose, linear or branched oligosaccharides, but was nonreactive against short branches; thus, no reducing sugars were detected. This is surprising as all currently known type I pullulanases produce reducing sugars (predominantly maltotriose) on digesting starch. The closest homologue of PulASK (95 % identity) is a type I pullulanase from Anoxybacillus sp. LM14-2 (Pul-LM14 2), which is capable of forming reducing sugars from starch. With rational design, amino acids 362-370 of PulASK were replaced with the corresponding sequence of Pul-LM14-2. The mutant enzyme formed reducing sugars on digesting starch. Thus, we identified a novel motif involved in substrate specificity in type I pullulanases. Our characterization may pave the way for the industrial application of this unique enzyme. PMID- 27000840 TI - Reversible S-nitrosylation limits over synthesis of fungal styrylpyrone upon nitric oxide burst. AB - Nitric oxide (NO) is known to be involved in modulating production of styrylpyrone polyphenols in the basidiomycete Inonotus obliquus. However, it remains unknown how NO orchestrates fungal styrylpyrone biosynthesis. Here, we show that a transient NO burst correlated with an enhanced expression of phenylalanine ammonia lyase (PAL), 4-coumarate CoA ligase (4CL), and styrylpyrone synthase (SPS), the key enzymes involved in styrylpyrone biosynthesis, and subsequently an increased production of styrylpyrone polyphenols. In parallel, the NO burst also resulted in S-nitrosylation of PAL, 4CL, and SPS, which compromised their enzymatic activities mediating a post-translational feedback mechanism that keeps NO-dependent transcriptional activation in check. Moreover, dysfunction of thioredoxin reductase (TrxR) further increased the formation of S nitrosylated proteins, implicating the significance of the Trx system in maintaining a low level of protein-nitrosothiols. Three thioredoxin-like proteins (TrxLs) from I. obliquus show in vitro denitrosylation potential toward S nitrosylated proteins via trans-denitrosylation or mixed disulfide intermediates. Thus, S-nitrosylation triggered by the NO burst limits over production of fungal styrylpyrone polyphenols, and denitrosylation by TrxLs that act in concert with TrxR play a key role in maintaining redox balance and orchestrating catalytic activities of the enzymes engaged in styrylpyrone synthetic metabolism. PMID- 27000841 TI - Nutrient recycling of lipid-extracted waste in the production of an oleaginous thraustochytrid. AB - Improving the economics of microalgae production for the recovery of microbial oil requires a comprehensive exploration of the measures needed to improve productivity as well as to reduce the overall processing costs. One avenue for cost reduction involves recycling the effluent waste water remaining after lipid extraction. This study investigates the feasibility of recycling those wastes for growing thraustochytrid biomass, a heterotrophic microalgae, where wastes were generated from the enzymatic extraction of the lipids from the cell biomass. It was demonstrated that secondary cultures of the tested thraustochytrid grown in the recycled wastes performed favorably in terms of cell and oil production (20.48 g cells L(-1) and 40.9 % (w/w) lipid) compared to the control (13.63 g cells L(-1) and 56.8 % (w/w) lipid). Further, the significant uptake of solubilized cell material (in the form of amino acids) demonstrated that the recycled waste has the potential for offsetting the need for fresh medium components. These results indicate that the implementation of a nutrient recycling strategy for industrial microalgae production could be possible, with significant added benefits such as conserving water resources, improving production efficiency, and decreasing material inputs. PMID- 27000842 TI - Time-trends in rates of hospital admission of adolescents for violent, self inflicted or drug/alcohol-related injury in England and Scotland, 2005-11: population-based analysis. AB - Background: Incidence of emergency admissions for violent injury in 10- to 18 year olds decreased in England and Scotland between 2005 and 2011, but more steeply in Scotland. To generate hypotheses about causes of these differences, we determined whether trends were consistent across admissions for three common types of adversity-related injury (violent, self-inflicted and drug/alcohol related). Methods: Emergency admissions to NHS hospitals were captured using Hospital Episode Statistics and Scottish Morbidity Records. Adversity-related injury was defined using ICD-10 codes. Analyses were stratified by sex/age groups (10-12, 13-15 and 16-18 years) and adjusted for background trends in admissions for injury. Results: During 2005-11, rates declined in all sex/age groups in Scotland (reductions adjusted for background trends ranged from -22.0 to 103.7/100 000) and in girls and boys aged <16 years in England (adjusted reductions -12.0 to -49.9/100 000). However, these rates increased in England for both sexes aged 16-18 years (adjusted increases, girls 71.8/100 000; boys 28.0/100 000). However, throughout 2005-11 overall rates remained relatively similar in England and Scotland for both sexes aged <16 years, and remained higher in Scotland for both sexes aged 16-18 years. Conclusions: A greater decline in the rates of emergency admissions for adversity-related injury for adolescents in Scotland compared with England could signal more effective policies in Scotland for reducing violence, self-harm, or drug/alcohol misuse, particularly for 16 to 18-year olds. PMID- 27000843 TI - The portrayal of infant feeding in British women's magazines: a qualitative and quantitative content analysis. AB - Background: Exclusive breastfeeding is the best start an infant can receive. However, in many high-income countries breastfeeding rates are low and this may be a reflection of social norms which in turn may be influenced by the media. This study therefore explored the portrayal of infant feeding in women's general interest magazines. Methods: The five top selling women's weekly magazines in Britain and Ireland for 2013 over a 4-month period were included. A quantitative and qualitative content analysis was conducted for both written and visual content. Results: In 58 magazines, there were 90 references to infant feeding with an average of 1.5 (range: 0-5) per magazine. Breastfeeding and formula feeding references were present in equal number and both were predominantly portrayed positively. There was only 1 visual representation of breast feeding compared with 11 of bottle feeding. Potential drivers for breastfeeding included its role in post-pregnancy weight loss and celebrity endorsement while family routine, the role of males in the house and concerns about adverse health effects were identified as barriers to breastfeeding. Conclusion: An improvement in visual representations of breast feeding and factual information in women's weekly magazines may be helpful in re-defining social norms regarding infant feeding. Keywords: food and nutrition, health promotion, public health. PMID- 27000844 TI - An investigation into the potential effects of infrapopulation structure and other sources of sampling error, on population genetic studies of the transmission of Schistosoma japonicum (Trematoda: Digenea). AB - BACKGROUND: Schistosoma japonicum remains a major challenge to human and animal health. Earlier microsatellite-based studies reported possible definitive-host specific private alleles within S. japonicum, opening the possibility that different definitive hosts might harbour different parasite strains. Previous investigations have also detected near-identical multilocus genotypes in populations of adult worms - possibly the result of mutations occurring during the asexual (intramolluscan) phase of clonal expansion. Research has also revealed extensive deviations from Hardy-Weinberg Proportions (HWP) and conflicting results among studies. The present study was performed to examine some of the potential effects of infrapopulation structure on microsatellite based studies of the transmission ecology of S. japonicum. Potential sources of bias considered included organotropic distribution of worms, non-random mating and corrections for clonal expansion. RESULTS: Stool samples from naturally infected hosts were used to infect snails in the laboratory and thereby expose mice. 274 individual worms were typed at seven microsatellite loci. Removal of individuals bearing duplicate MLGs (as a correction for presumed clonal expansion) had an impact on both HWP and organotropic genetic differentiation. The study found no evidence that heterozygote deficiencies were caused by a Wahlund effect. Female-male pairings appeared to be random and there was no evidence for mate choice by heterozygosity. There was some indication that excess heterozygosity, induced by clonal expansion, can offset heterozygote deficiencies caused by small population size or populations fragmented by parasite control efforts. CONCLUSIONS: The view is supported that miracidia are preferable to adult worms in investigations into host-specific parasite lineages. Where adults must be used, extreme care should be taken with regard to sampling if infrapopulations of small animals are compared with those of larger animals; this is because of organotropic patterns in genetic variation and the tendency to sample from different organs in differently sized hosts. As corrections for clones may accentuate signals of population subdivision, corrections should only be made if tests for clonal expansion prove positive. Finally, evidence for heterozygote deficiency caused by small sample size, calls for carefully designed random and comprehensive sampling strategies for S. japonicum in China, where control efforts have greatly fragmented parasite populations. PMID- 27000846 TI - Comment on Ueno et al.: Prevalence of laparoscopic surgical treatment and its clinical outcomes in patients with familial adenomatous polyposis in Japan. PMID- 27000845 TI - Prognostic value of glucosylceramide synthase and P-glycoprotein expression in oral cavity cancer. AB - BACKGROUND: Glucosylceramide synthase (GCS) and P-glycoprotein (P-gp) overexpression are associated with multidrug resistance in several human cancers. This study investigated the prognostic value of GCS and P-gp in oral cavity squamous cell carcinoma (OSCC). METHODS: The association between GCS and P-gp overexpression and clinical outcomes was assessed in 186 human clinical specimens of primary tumors obtained from curative surgery. Immunohistochemistry staining results were scored as high or low for GCS, and positive or negative for P-gp. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables. RESULTS: GCS overexpression was observed in 128 (68.8 %) patients and P-gp overexpression in 43 (23.1 %) patients. High GCS expression was significantly correlated with P-gp immunopositivity (P = 0.005). GCS and P-gp overexpression was significantly correlated with cervical nodal metastasis (P < 0.05). Univariate analyses showed that tumor lymphovascular invasion, positive neck lymph nodes, advanced overall TNM stage, high GCS expression, and P-gp immunopositivity were associated with poor locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) (P < 0.05). Multivariate analyses showed that lymphovascular invasion, nodal positivity, and P-gp overexpression remained independent prognostic variables for LRC, DFS, and OS, and that GCS expression was an independent predictor of LRC and DFS (P < 0.05). CONCLUSION: GCS and P-gp expression is associated with poor prognosis, suggesting suitability as novel biomarkers in OSCC. PMID- 27000847 TI - A critical analysis of the review on antimicrobial resistance report and the infectious disease financing facility. AB - Over the past year, two major policy initiatives have been introduced focusing on stimulating antibiotic development for human consumption. The European Investment Bank has announced the development of the Infectious Disease Financing Facility (IDFF) and the British government commissioned the Review on Antimicrobial Resistance, led by Jim O'Neill. Each constitutes a major effort by the European community to address the evolving crisis of antimicrobial resistance. Though both have similar goals, the approaches are unique and worthy of consideration.This manuscript utilizes a previously published framework for evaluation of antibiotic incentive plans to clearly identify the strengths and weaknesses of each proposal. The merits of each proposal are evaluated in how they satisfy four key objectives: 1) Improve the overall net present value (NPV) for new antibiotic projects; 2) Enable greater participation of Small to Medium Sized Enterprises (SME); 3) Encourage participation by large pharmaceutical companies; 4) Facilitate cooperation and synergy across the antibiotic market. The IDFF seeks to make forgivable loans to corporations with promising compounds, while the O'Neill group proposes a more comprehensive framework of early stage funding, along with the creation of a stable global market.Ultimately, the proposals may prove complementary and if implemented together may form a more comprehensive plan to address an impending global crisis. Substantial progress will only be made on these efforts if action is taken at an international level, therefore we recommend consideration of these efforts at the upcoming G20 summit. PMID- 27000848 TI - Paternal Lifelong Socioeconomic Position and Low Birth Weight Rates: Relevance to the African-American Women's Birth Outcome Disadvantage. AB - Objectives To determine the relation of paternal lifelong socioeconomic position (SEP) to the racial disparity in low birth weight (<2500 g, LBW) rates. Methods Stratified and multilevel logistic regression analyses were performed on an Illinois transgenerational dataset of infants (1989-1991) and their parents (1956 1976) with appended U.S. census income data. The neighborhood incomes of father's place of residence at the time of his birth and at the time of his infant's birth were used to measure of lifelong SEP. Population attributable risk (PAR) percentages were calculated to estimate the percentage of LBW infants attributable to paternal low SEP. Results In Cook County, infants (n = 10,168) born to fathers with a lifelong high SEP had a LBW rate of 3.7 %. LBW rates rose among infants born to fathers with early-life (n = 7224), adulthood (n = 2913), or lifelong (n = 7288) low SEP: 5.2, 6.9, and 9.3 %, respectively. The adjusted (controlling for maternal demographic characteristics) OR of LBW for fathers with an early-life, adulthood, or lifelong low (compared to lifelong high) SEP equaled 1.4 (1.2, 1.6), 1.5 (1.3, 1.9), and 2.0 (1.7, 2.3), respectively. The PAR percentages of LBW for paternal low SEP were 40 and 9 % among African-American and White mothers, respectively. Among fathers with a lifelong high SEP, the adjusted OR of LBW for African-American (compared to White) mothers was 1.1 (0.7, 1.7). Conclusions Low paternal SEP is a novel risk factor for infant LBW independent of maternal demographic characteristics. This phenomenon is particularly relevant to the African-American women's birth outcome disadvantage. PMID- 27000849 TI - Racial Differences in DNA-Methylation of CpG Sites Within Preterm-Promoting Genes and Gene Variants. AB - Objective To evaluate the role DNA methylation may play in genes associated with preterm birth for higher rates of preterm births in African-American women. Methods Fetal cord blood samples from births collected at delivery and maternal demographic and medical information were used in a cross-sectional study to examine fetal DNA methylation of genes implicated in preterm birth among black and non-black infants. Allele-specific DNA methylation analysis was performed using a methylation bead array. Targeted maximum likelihood estimation was applied to examine the relationship between race and fetal DNA methylation of candidate preterm birth genes. Receiver-operating characteristic analyses were then conducted to validate the CpG site methylation marker within the two racial groups. Bootstrapping, a method of validation and replication, was employed. Results 42 CpG sites were screened within 20 candidate gene variants reported consistently in the literature as being associated with preterm birth. Of these, three CpG sites on TNFAIP8 and PON1 genes (corresponding to: cg23917399; cg07086380; and cg07404485, respectively) were significantly differentially methylated between black and non-black individuals. The three CpG sites showed lower methylation status among infants of black women. Bootstrapping validated and replicated results. Conclusion for Practice Our study identified significant differences in levels of methylation on specific genes between black and non black individuals. Understanding the genetic/epigenetic mechanisms that lead to preterm birth may lead to enhanced prevention strategies to reduce morbidity and mortality by eventually providing a means to identify individuals with a genetic predisposition to preterm labor. PMID- 27000850 TI - Racial/Ethnic Disparities in the Association Between Preeclampsia Risk Factors and Preeclampsia Among Women Residing in Hawaii. AB - Objective To assess differences in the rates of preeclampsia among a multiethnic population in Hawaii. Methods We performed a retrospective study on statewide inpatient data for delivery hospitalizations in Hawaii between January 1995 and December 2013. Multivariable logistic regression was used to assess the impact of maternal race/ethnicity on the rates of preeclampsia after adjusting for age, multiple gestation, multiparity, chronic hypertension, pregestational diabetes, obesity and smoking. Results A total of 271,569 hospital discharges for delivery were studied. The rates of preeclampsia ranged from 2.0 % for Chinese to 4.6 % for Filipinos. Preeclampsia rates were higher among Native Hawaiians who are age <35 and non-obese (OR 1.54; 95 % CI 1.43-1.66), age >=35 and non-obese (OR 2.31; 95 % CI 2.00-2.68), age >=35 and obese (OR 1.80; 95 % CI 1.24-2.60); other Pacific Islanders who are age <35 and non-obese (OR 1.40; 95 % CI 1.27-1.54), age >=35 and non-obese (OR 2.18; 95 % CI 1.79-2.64), age >=35 and obese (OR 1.68; 95 % CI 1.14-2.49); and Filipinos who are age <35 and non-obese (OR 1.55; 95 % CI 1.43-1.67), age >=35 and non-obese (OR 2.26; 95 % CI 1.97-2.60), age >=35 and obese (OR 1.64; 95 % CI 1.04-2.59) compared to whites. Pregestational diabetes (OR 3.41; 95 % CI 3.02-3.85), chronic hypertension (OR 5.98; 95 % CI 4.98-7.18), and smoking (OR 1.19; 95 % CI 1.07-1.33) were also independently associated with preeclampsia. Conclusions for Practice In Hawaii, Native Hawaiians, other Pacific Islanders and Filipinos have a higher risk of preeclampsia compared to whites. For these high-risk ethnic groups, more frequent monitoring for preeclampsia may be needed. PMID- 27000852 TI - Erratum to: Quantitative assessment of atherosclerotic plaques on 18F-FDG PET/MRI: comparison with a PET/CT hybrid system. PMID- 27000851 TI - Multi-Functional Diarylurea Small Molecule Inhibitors of TRPV1 with Therapeutic Potential for Neuroinflammation. AB - Transient receptor potential vanilloid type 1 (TRPV1), a heat-sensitive calcium channel protein, contributes to inflammation as well as to acute and persistent pain. Since TRPV1 occupies a central position in pathways of neuronal inflammatory signaling, it represents a highly attractive potential therapeutic target for neuroinflammation. In the present work, we have in silico identified a series of diarylurea analogues for hTRPV1, of which 11 compounds showed activity in the nanomolar to micromolar range as validated by in vitro biological assays. Then, we utilized molecular docking to explore the detailed interactions between TRPV1 and the compounds to understand the contributions of the different substituent groups. Tyr511, Leu518, Leu547, Thr550, Asn551, Arg557, and Leu670 were important for the recognition of the small molecules by TRPV1. A hydrophobic group in R2 or a polar/hydrophilic group in R1 contributed significantly to the activities of the antagonists at TRPV1. In addition, the subtle different binding pose of meta-chloro in place of para-fluoro in the R2 group converted antagonism into partial agonism, as was predicted by our short-term molecular dynamics (MD) simulation and validated by bioassay. Importantly, compound 15, one of our best TRPV1 inhibitors, also showed potential binding affinity (1.39 MUM) at cannabinoid receptor 2 (CB2), which is another attractive target for immuno inflammation diseases. Furthermore, compound 1 and its diarylurea analogues were predicted to target the C-X-C chemokine receptor 2 (CXCR2), although bioassay validation of CXCR2 with these compounds still needs to be performed. This prediction from the modeling is of interest, since CXCR2 is also a potential therapeutic target for chronic inflammatory diseases. Our findings provide novel strategies to develop a small molecule inhibitor to simultaneously target two or more inflammation-related proteins for the treatment of a wide range of inflammatory disorders including neuroinflammation and neurodegenerative diseases with potential synergistic effect. PMID- 27000853 TI - Erratum to: 18F-FDG PET/MRI evaluation of retroperitoneal fibrosis: a simultaneous multiparametric approach for diagnosing active disease. PMID- 27000854 TI - Endothelial Dysfunction in Obesity: Role of Inflammation. AB - Endothelium modulates vascular function and structure, mainly by production of nitric oxide which protects the vasculature against the development of atherosclerosis and thrombosis. Abdominal obesity is associated with vascular endothelial dysfunction, caused by a reduced nitric oxide availability secondary to an enhanced oxidative stress production. Pro-inflammatory cytokine generation is a major mechanism whereby obesity is associated with a reduced NO availability. In healthy conditions, perivascular adipose tissue (PVAT) secretes factors that influence vasodilation by increasing NO availability. Such protective effect is lost in PVAT from obese subjects, which in turn is switched towards a functionally active pro-contractile inflammation source, causing a reduction of vascular NO availability and contributing to the endothelin-1/NO imbalance. In such context, vasculature not only represents a main target of PVAT derived pro-inflammatory cytokines, but is also considered as important source of low-grade inflammation and oxidative stress which, together with the PVAT, contribute to endothelial dysfunction which characterizes obese patients. PMID- 27000855 TI - Relative compatibility of Schistosoma mansoni with Biomphalaria sudanica and B. pfeifferi from Kenya as assessed by PCR amplification of the S. mansoni ND5 gene in conjunction with traditional methods. AB - BACKGROUND: Schistosoma mansoni is hosted by several species of Biomphalaria spp. snails in Africa. We were interested in determining if there were differences in compatibility of S. mansoni with Biomphalaria sudanica from Lake Victoria, or with B. pfeifferi from streams and smaller water bodies in Kenya. Does this parasite develop with equal efficiency in both snail species, and does this have implications for transmission in different habitat types? METHODS: Primers for PCR amplification of the S. mansoni ND5 gene were designed and tested for sensitivity and specificity. We exposed laboratory-reared B. sudanica and field derived B. pfeifferi to single miracidium infections and at 1, 2, 4, 8, 16 and 24 days post-exposure (dpe), snails were extracted for the PCR assay. Snails were also shed for cercariae and/or dissected prior to extraction. Additionally, B. sudanica and B. pfeifferi were collected from field locations and tested with the PCR assay. RESULTS: The ND5 PCR assay was sensitive (>0.1 fg S. mansoni genomic DNA) and allowed S. mansoni to be differentiated from other relevant schistosome species or snails. The number of PCR positive snails at 1-4 dpe was higher for B. pfeifferi than for B. sudanica, but not significantly so (P = 0.052). From 8-24 dpe, more B. pfeifferi harbored successfully developing parasites (positive by both dissection and PCR) than did B. sudanica (P = 0.008). At 40 dpe, more B. pfeifferi than B. sudanica shed cercariae or harbored dissection positive/PCR positive infections (P < 0.001). Both immature and failed (dissection negative but PCR positive) S. mansoni infections could also be detected in naturally infected snails of both species. CONCLUSIONS: The PCR assay detected S. mansoni infections in snails exposed to one miracidium for one day. Both B. sudanica and B. pfeifferi supported full development of S. mansoni, but B. pfeifferi was more compatible, with significantly more dissection positive/PCR positive or shedding infections, and significantly fewer failed infections (dissection negative/PCR positive). This highlights the relatively lower compatibility of B. sudanica with S. mansoni, and suggests the factors responsible for incompatibility and how they might affect transmission of S. mansoni in habitats like Lake Victoria deserve additional study. PMID- 27000856 TI - The use of the PEN3 e-nose in the screening of colorectal cancer and polyps. PMID- 27000857 TI - Posterior high sacral segmental disconnection prior to anterior en bloc exenteration for recurrent rectal cancer. AB - This article describes a novel technique for en bloc resection of locally recurrent rectal cancer that invades the high sacral bone (above S3). The involved segment of the sacrum is mobilised with osteotomes during an initial posterior approach before an anterior abdominal phase where the segment of sacral bone is delivered with the specimen. This allows en bloc resection of the involved sacrum while preserving uninvolved distal and contralateral sacral bone and nerve roots. The goal is to obtain a clear bony margin and offer a chance of cure while improving functional outcomes by maintaining pelvic stability and minimising neurological deficit. PMID- 27000858 TI - A new stomaplasty ring (KoringTM) to prevent parastomal hernia: an observational multicenter Swiss study. AB - BACKGROUND: Parastomal hernias (PSH) are one of the most frequent complications of enterostomies with a non-negligible complication rate and a significant socioeconomic effect. Therefore, preventing PSH by placing a mesh at the time of primary surgery has been advocated. The aim of our study was to evaluate the safety and feasibility of the new stomaplasty ring [KoringTM, (Koring GmbH, Basel, Switzerland)] and investigate the reason why surgeons are reluctant to take preventive measures. METHODS: A multicenter observational study was conducted on 30 patients between December 2013 and January 2015. In permanent end colostomies and end ileostomies, the KoringTM was implanted. The primary outcome was the 30-day morbidity (infection and other stoma-related complications). Secondary endpoints were the technical feasibility and the time needed to fix the ring. In addition, an online survey of 107 surgeons was performed. RESULTS: Twenty-seven patients received permanent end colostomies, and three received end ileostomies. No stoma-related complication was detected within the first 30 days post-operatively. The KoringTM ring was evaluated by the surgeons as easy and very easy to implant in more than half of the patients. Average additional operating time for ring implantation was 19 min. CONCLUSIONS: KoringTM implantation at the time of creating the stoma is safe, easy and only adds minimally operating time. A long-term follow-up as well as a randomized controlled study is needed to evaluate the impact of the KoringTM on PSH prevention. The ease and rapidity with which KoringTM can be implanted may help surgeons to overcome their apprehension of using a preventative device. PMID- 27000859 TI - Physalin A induces G2/M phase cell cycle arrest in human non-small cell lung cancer cells: involvement of the p38 MAPK/ROS pathway. AB - Physalin A (PA) is an active withanolide isolated from Physalis alkekengi var. franchetii, a traditional Chinese herbal medicine named Jindenglong, which has long been used for the treatment of sore throat, hepatitis, and tumors in China. In the present study, we firstly investigated the effects of PA on proliferation and cell cycle distribution of the human non-small cell lung cancer (NSCLC) A549 cell line, and the potential mechanisms involved. Here, PA inhibited cell growth in dose- and time-dependent manners. Treatment of A549 cells with 28.4 MUM PA for 24 h resulted in approximately 50 % cell death. PA increased the amount of intracellular ROS and the proportion of cells in G2/M. G2/M arrest was attenuated by the addition of ROS scavenger NAC. ERK and P38 were triggered by PA through phosphorylation in a time-dependent manner. The phosphorylation of ERK and P38 were not attenuated by the addition of NAC, but the use of the p38 inhibitor could reduce, at least in part, PA-induced ROS and the proportion of cells in G2/M. PA induces G2/M cell cycle arrest in A549 cells involving in the p38 MAPK/ROS pathway. This study suggests that PA might be a promising therapeutic agent against NSCLC. PMID- 27000862 TI - The "watering can perineum". PMID- 27000861 TI - Impact and mechanistic role of oral contraceptive pills on the number and epithelial type of ovarian cortical inclusion cysts; a clinicopathology and immunohistochemical study. AB - BACKGROUND: Ovarian epithelial cancers are among the most lethal women's cancers. There is no doubt about the preventive role of oral contraceptive pills (OCPs) in development of ovarian cancers. But, there are limited numbers of studies to address the effect of these agents on the number of cortical inclusion cysts (CICs), their epithelial type and suppression of the metaplastic phenomenon by these pills. The aim of this study was to clarify the role of these agents in the prevention of these cyst formation and tubal metaplasia and also examine the mesenchymal-epithelial transition theory in this context by immunohistochemical methods. METHODS: The representative section(s) of ovarian cortex from a total number of 201 consecutive total abdominal hysterectomy with bilateral or unilateral salpingo-oophorectomy specimens were examined for mean number of CICs and their epithelial type between two groups of the patients. Group A included the patients who were on oral contraceptive pills for more than 5 years. All of the subjects with other contraceptive methods or a history of less than 5 years contraceptive pills usage were stratified in group B. Sections from 20 cases in which more than five inclusion cysts were found, were selected for IHC staining with calretinine and PAX8 as markers for mesothelium and mullerian epithelium respectively. RESULTS: The mean age of the patients was 51.67 years with no significant differences between two groups. The mean number of cysts were 1.27 and 3.23 in group A and B respectively (P =0.0001). Similarly the mean number of CICs, lined by tubal epithelium, was significantly different between two groups (0.65 vs 2.65, P =0.0001). In IHC staining 123 out of 150 CICs (82 %) were PAX+ while only 7 CICs (4.8 %) showed positive reaction for calretinin irrespective of type of epithelium. CONCLUSION: Our findings showed that the use of OCP for more than five years in women, significantly prevents development of cortical inclusion cysts in the ovaries which lined by tubal (PAX8 positive) type epithelium. These findings may explain the alternative mechanism of oral contraceptive pills or long time use of progesterone in suppression of tubal type overgrowth and subsequently prevention of ovarian epithelial cancers. PMID- 27000860 TI - Downregulation and tumor-suppressive role of XPO5 in hepatocellular carcinoma. AB - XPO5 (Exp5, Exportin-5) is a transporter protein mainly mediating pre-microRNAs' nuclear export. Recent studies have demonstrated that XPO5 may play crucial roles in a few of cancers. However, little is known about XPO5 in hepatocellular carcinoma (HCC). In the present study, we elucidated the expression of XPO5 by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining in HCC samples and conducted several functional analyses to address its effects on HCC development. The results demonstrated that both mRNA and protein levels of XPO5 were downregulated in HCC tissues compared to adjacent non-cancerous livers. Ectopic expression of XPO5 significantly suppressed cell proliferation, colony formation, growth in soft agar, and tumorigenicity in nude mice, whereas knockdown of XPO5 by RNA inference showed opposite phenotypes. Moreover, XPO5 knockdown promoted HCC cell migration and decreased the expression of E-cadherin and p53. Additionally, after treatment with DAC and TSA, the mRNA level of XPO5 was upregulated in HCC cells tested, implicating that epigenetic modulation may be involved in the transcription of XPO5. Collectively, our findings suggest that XPO5 functions as a potential tumor suppressor in the development and progression of HCC as well as a promising molecular target for HCC therapy. PMID- 27000863 TI - The "abdominal cocoon". PMID- 27000864 TI - Relationship between FEV1 and arterial stiffness in elderly people with chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is highly prevalent in the elderly, and both COPD and age per se are associated with cardiovascular morbidity. AIMS: We tested the hypothesis that in elderly COPD patients airflow limitation is associated with arterial stiffness and the relationship, if any, is related to endothelial function and systemic inflammation. METHODS: We evaluated lung function, augmentation index (AIx), flow-mediated dilation (FMD), Interleukin-6 (IL-6), and asymmetric dymethilarginine (ADMA) levels in 76 subjects (mean age 73.9 years, SD 6.2) attending a geriatric outpatient clinic. RESULTS: Participants with COPD (N = 41) and controls (N = 35) did not differ in terms of AIx (30 vs 28.2 %, P = 0.30) and FMD (14.2 vs 12.3 %, P = 0.10). Similarly, the two groups did not differ with respect to mean concentrations of inflammation markers (IL-6 and C-reactive protein) and ADMA. Among COPD participants there was an inverse correlation between AIx and Forced Expiratory Volume in the first second (r = -0.349, P = 0.02). This relationship remained significant after correction for potential confounders, including markers of inflammation and ADMA levels (beta = -0.194, P = 0.001). DISCUSSION: According to the results of this study, among COPD patients, bronchial patency and AIx are inversely related, and the relationship is explained neither by endothelial function nor by systemic inflammation. CONCLUSIONS: In elderly COPD people, increased arterial stiffness is related to reduced pulmonary function and it seems worth testing as a potential marker of higher cardiovascular risk. PMID- 27000865 TI - Does the reason for discontinuation of a first TNF inhibitor influence the effectiveness of a second TNF inhibitor in axial spondyloarthritis? Results from the Swiss Clinical Quality Management Cohort. AB - BACKGROUND: With regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA), conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi. METHODS: Patients with a clinical diagnosis of axSpA starting a second TNFi in the Swiss Clinical Quality Management cohort were included. Effectiveness of treatment at 1 year, as well as drug survival, was compared between subgroups having discontinued the first TNFi because of lack of response, adverse events (AEs), or other reasons. Lack of response was further divided into primary or secondary lack of response (PLR or SLR, respectively), depending on whether the first TNFi was stopped before or after 6 months of treatment. RESULTS: Among 632 patients with axSpA, median survival of a second TNFi was 1.1 years after PLR and 3.8 years after SLR (p = 0.003). At least moderate disease activity as defined by an Ankylosing Spondylitis Disease Activity Score using the erythrocyte sedimentation rate (ASDAS-ESR) <2.1 was achieved after 12 months by 11 %, 39 %, 26 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). Only 4 % of patients achieved an ASDAS-ESR inactive disease state after PLR, in comparison to 22 % of those after SLR. Similar results were demonstrated in patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA (n = 488): ASDAS-ESR <2.1 was achieved after 12 months by 9 %, 41 %, 29 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). CONCLUSIONS: The effectiveness of a second TNFi is significantly impaired in patients with axSpA after PLR to a first TNFi compared with SLR. PMID- 27000866 TI - Use of Tigecycline in Pediatric Patients With Infections Predominantly Due to Extensively Drug-Resistant Gram-Negative Bacteria. AB - Background.: Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases. Methods.: We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed. Results.: In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for >=2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009). Conclusions.: Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients. PMID- 27000867 TI - Fulminant Endophthalmitis in a Child Caused by Neisseria meningitidis Serogroup C Detected by Specific DNA. AB - This case report describes a local Neisseria meningitidis eye infection with a long protracted course in a seemingly healthy previously vaccinated child. Bacterial infection was detected by polymerase chain reaction techniques. PMID- 27000868 TI - Glycerolipidome responses to freezing- and chilling-induced injuries: examples in Arabidopsis and rice. AB - BACKGROUND: Glycerolipids are the principal constituent of cellular membranes; remodelling of glycerolipids plays important roles in temperature adaptation in plants. Temperate plants can endure freezing stress, but even chilling at above zero temperatures can induce death in tropical species. However, little is known about the differences in glycerolipid response to low temperatures between chilling-sensitive and freezing-tolerant plants. Using ESI-MS/MS-based lipidomic analysis, we compared the glycerolipidome of chilling (4 and 10 degrees C) treated rice with that of freezing (-6 and -12 degrees C)-treated Arabidopsis, both immediately after these low-temperature treatments and after a subsequent recovery culture period. RESULTS: Arabidopsis is a 16:3 plant that harbours both eukaryotic and prokaryotic-type lipid synthesis pathways, while rice is an 18:3 plant that harbours only the eukaryotic lipid synthesis pathway. Arabidopsis contains higher levels of galactolipids than rice and has a higher double bond index (DBI). Arabidopsis contains lower levels of high melting point phosphatidylglycerol (PG) molecules and has a lower average acyl chain length (ACL). Marked phospholipid degradation occurred during the recovery culture period of non-lethal chilling treated rice, but did not occur in non-lethal freezing treated Arabidopsis. Glycerolipids with larger head groups were synthesized more in Arabidopsis than in rice at sub-lethal low-temperatures. Levels of phosphatidic acid (PA) and phosphatidylinositol (PI) rose in both plants after low-temperature treatment. The DBI and ACL of total lipids did not change during low-temperature treatment. CONCLUSIONS: A higher DBI and a lower ACL could make the membranes of Arabidopsis more fluid at low temperatures. The ability to synthesize glycerolipids containing a larger head group may correlate with low-temperature tolerance. The low-temperature-induced increase of PA may play a dual role in plant responses to low temperatures: as a lipid signal that initiates tolerance responses, and as a structural molecule that, on extensive in large accumulation, could damage the integrity of membranes. Changes in ACL and DBI are responses of plants to long-term low temperature. PMID- 27000869 TI - Non-small-cell lung cancer-induced immunosuppression by increased human regulatory T cells via Foxp3 promoter demethylation. AB - Patients with non-small-cell lung cancer (NSCLC) have immune defects that are poorly understood. Forkhead box protein P3 (Foxp3) is crucial for immunosuppression by CD4(+) regulatory T cells (Tregs). It is not well known how NSCLC induces Foxp3 expression and causes immunosuppression in tumor-bearing patients. Our study found a higher percentage of CD4(+) Tregs in the peripheral blood of NSCLC compared with healthy donors. NSCLC patients showed demethylation of eight CpG sites within the Foxp3 promoter with methylation ratios negatively correlated with CD4(+)CD25(+)Foxp3(+) T levels. Foxp3 expression in CD4(+) Tregs was directly regulated by Foxp3 promoter demethylation and was involved in immunosuppression by NSCLC. To verify the effect of tumor cells on the phenotype and function of CD4(+) Tregs, we established a coculture system using NSCLC cell line and healthy CD4(+) T cells and showed that SPC-A1 induced IL-10 and TGF beta1 secretion by affecting the function of CD4(+) Tregs. The activity of DNA methyltransferases from CD4(+) T was decreased during this process. Furthermore, eight CpG sites within the Foxp3 promoter also appeared to have undergone demethylation. Foxp3 is highly expressed in CD4(+) T cells, and this may be caused by gene promoter demethylation. These induced Tregs are highly immunosuppressive and dramatically inhibit the proliferative activity of naive CD4(+) T cells. Our study provides one possible mechanism describing Foxp3 promoter demethylation changes by which NSCLC down-regulates immune responses and contributes to tumor progression. Foxp3 represents an important target for NSCLC anti-tumor immunotherapy. PMID- 27000870 TI - Altered serum levels of kynurenine metabolites in patients affected by cluster headache. AB - BACKGROUND: The reported efficacy of memantine in the treatment of patients with cluster headache (CH) suggests that NMDA receptors are involved in mechanisms of nociceptive sensitization within the trigeminal system associated with CH. NMDA receptors are activated or inhibited by neuroactive compounds generated by tryptophan metabolism through the kynurenine pathway. In the accompanying manuscript, we have found that serum levels of all kynurenine metabolites are altered in patients with chronic migraine. Here, we have extended the study to patients affected by episodic or chronic CH as compared to healthy controls. METHOD: We assessed serum levels of kynurenine (KYN), kynurenic Acid (KYNA), anthranilic acid (ANA), 3-hydroxy-anthranilic acid (3-HANA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), quinolinic acid (QUINA), tryptophan (Trp) and 5 hydroxyindolacetic acid (5-HIAA) by means of a liquid chromatography/tandem mass spectrometry (LC/MS-MS) method in 21 patients affected by CH (15 with episodic and 6 with chronic CH), and 35 age-matched healthy subjects. Patients with psychiatric co-morbidities, systemic inflammatory, endocrine or neurological disorders, and mental retardation were excluded. RESULTS: LC/MS-MS analysis of kynurenine metabolites showed significant reductions in the levels of KYN (-36 %), KYNA (-34 %), 3-HK (-51 %), 3-HANA (-54 %), XA (-25 %), 5-HIAA (-39 %) and QUINA (-43 %) in the serum of the overall population of patients affected by CH, as compared to healthy controls. Serum levels of Trp and ANA were instead significantly increased in CH patients (+18 % and +54 %, respectively). There was no difference in levels of any metabolite between patients affected by episodic and chronic CH, with the exception of KYN levels, which were higher in patients with chronic CH. CONCLUSION: The reduced levels of KYNA (an NMDA receptor antagonist) support the hypothesis that NMDA receptors are overactive in CH. A similar reduction in KYNA levels was shown in the accompanying manuscript in patients affected by chronic migraine. The reduced levels of XA, a putative analgesic compound, may contribute to explain the severity of pain attacks in CH. These data, associated with the data reported in the accompanying manuscript, supports a role for the kynurenine pathway in the pathophysiology of chronic headache disorders. PMID- 27000871 TI - Advances in personalized cancer immunotherapy. AB - There are currently three major approaches to T cell-based cancer immunotherapy, namely, active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Recently, this latter approach has demonstrated remarkable clinical benefits, putting cancer immunotherapy under the spotlight. Better understanding of the dynamics of anti-tumor immune responses (the "Cancer-Immunity Cycle") is crucial for the further development of this form of treatment. Tumors employ multiple strategies to escape from anti-tumor immunity, some of which result from the selection of cancer cells with immunosuppressive activity by the process of cancer immunoediting. Apart from this selective process, anti-tumor immune responses can also be inhibited in multiple different ways which vary from patient to patient. This implies that cancer immunotherapy must be personalized to (1) identify the rate-limiting steps in any given patient, (2) identify and combine strategies to overcome these hurdles, and (3) proceed with the next round of the "Cancer-Immunity Cycle". Cancer cells have genetic alterations which can provide the immune system with targets by which to recognize and eradicate the tumor. Mutated proteins expressed exclusively in cancer cells and recognizable by the immune system are known as neoantigens. The development of next-generation sequencing technology has made it possible to determine the genetic landscape of human cancer and facilitated the utilization of genomic information to identify such candidate neoantigens in individual cancers. Future immunotherapies will need to be personalized in terms of the identification of both patient-specific immunosuppressive mechanisms and target neoantigens. PMID- 27000872 TI - Quantitative trait loci analysis and genome-wide comparison for silique related traits in Brassica napus. AB - BACKGROUND: Yield of rapeseed is determined by three components: silique number, seed number per silique and thousand seed weight. Seed number per silique and thousand seed weight are influenced by silique length, seed density, silique breadth, silique thickness and silique volume. Some QTLs for silique traits have been reported in B. napus, however, no studies have focused on the six agronomic traits (seed number per silique, silique length, silique breadth, silique thickness, seed density and silique volume) simultaneously, and the genetic determinism of such complex traits have not been fully elucidated. RESULTS: In this study, the six silique traits were evaluated using 348 lines of a doubled haploid population, the KN population. The results showed that 2, 4, 1, 1 and 2 QTLs explaining > 10 % of phenotypic variation were obtained for silique length, silique breadth, silique thickness, seed number per silique and silique volume, respectively. Notably, three major effect QTLs (cqSB-C6-1, cqSB-C6-2 and cqSV-C6 3) were identified in at least three environments, and 17 unique QTLs controlling at least two traits were obtained. A high-density consensus map containing 1225 markers was constructed for QTL comparison by combining the KN map with other five published maps. The comparative results revealed that 14, 13 and 11 QTLs for silique breadth, silique thickness and silique volume might be the potential new QTLs because few QTLs for these traits were reported in B. napus. In addition, potential new QTLs for silique length (11), seed number per silique (6) and seed density (5) were also identified. Twenty-five candidate genes underlying 27 QTLs for silique related traits were obtained. CONCLUSIONS: This study constructed QTL analysis in B. napus, and obtained 60 consensus QTLs for six silique related traits. The potential new QTLs will enhance our understanding of the genetic control of silique traits, and the stable QTLs provided the targets for improving seed yield in future. These findings provided comprehensive insights into the genetic network affecting silique traits at QTL level in B. napus. PMID- 27000873 TI - Toxigenic Corynebacterium ulcerans isolated from a wild bird (ural owl) and its feed (shrew-moles): comparison of molecular types with human isolates. AB - BACKGROUND: Corynebacterium ulcerans is a pathogen causing diphtheria-like illness to humans. In contrast to diphtheria by Corynebacterium diphtheriae circulating mostly among humans, C. ulcerans infection is zoonotic. The present study aimed to clarify how a zoonotic pathogen C. ulcerans circulates among wild birds and animals. RESULTS: By screening 380 birds, a single strain of toxigenic C. ulcerans was isolated from a carnivorous bird, ural owl (Strix uralensis). The bacterium was also isolated from two individuals of Japanese shrew-mole (Urotrichus talpoides), a food preference of the owl. Analysis by ribotyping showed that the owl and mole isolates were classified in a group, suggesting that C. ulcerans can be transmissible among wild birds and their prey animals. Moreover, our isolates were found to belong to a group of previously reported C. ulcerans isolates from dogs and a cat, which are known to serve as sources for human infection. CONCLUSION: The findings suggest that the shrew-mole may be a potential reservoir of a zoonotic pathogen C. ulcerans. PMID- 27000874 TI - Outcomes of Laparoscopic Liver Resection for Patients with Large Colorectal Liver Metastases: A Case-Matched Analysis. AB - BACKGROUND: Despite the expansion of laparoscopic approach in the treatment of liver tumors, limited data have been reported regarding large colorectal liver metastases (CRLMs). This study aimed at assessing the short- and long-term outcomes after laparoscopic liver resection (LLR) for large (>=5 cm) CRLMs. METHODS: This was a case-matched study (1:2) comparing patients with large (group L; >=5 cm) and small (group S; <5 cm) CRLMs using demographic, tumor, and surgical characteristics as matching variables. Postoperative outcomes and survival data were compared in the 2 groups. RESULTS: Forty patients who underwent LLR for large CRLMs were matched with 80 patients with tumors <5 cm. Major hepatectomy was performed with 75.0 % of patients in Group L and 66.3 % in group S (p = 0.403). Operative time was 300 min in group L and 240 min in group S (p = 0.059). The postoperative mortality and overall morbidity rates were comparable in the 2 groups (p = 1.000 and 0.170, respectively). Postoperative major complication (Dindo-Clavien >=3) was similar between the two groups (p = 0.072). R0 resection was achieved in 92.5 % in the group L and in 95.0 % in the group S (p = 1.000). The 5-year overall survival and recurrence-free survival were better for group S than for group L (47.3 vs. 35.4 %, p = 0.044 and 27.3 vs. 14.9 %, p = 0.042, respectively). Multivariate analysis identified positive surgical margins and synchronous presentation as prognostic factors. CONCLUSION: Since LLR was performed safely with favorable oncological adequacy in selected patients with large CRLMs, tumor size should not modify the surgical approach. PMID- 27000875 TI - Quantifying the effect of crop spatial arrangement on weed suppression using functional-structural plant modelling. AB - Suppression of weed growth in a crop canopy can be enhanced by improving crop competitiveness. One way to achieve this is by modifying the crop planting pattern. In this study, we addressed the question to what extent a uniform planting pattern increases the ability of a crop to compete with weed plants for light compared to a random and a row planting pattern, and how this ability relates to crop and weed plant density as well as the relative time of emergence of the weed. To this end, we adopted the functional-structural plant modelling approach which allowed us to explicitly include the 3D spatial configuration of the crop-weed canopy and to simulate intra- and interspecific competition between individual plants for light. Based on results of simulated leaf area development, canopy photosynthesis and biomass growth of the crop, we conclude that differences between planting pattern were small, particularly if compared to the effects of relative time of emergence of the weed, weed density and crop density. Nevertheless, analysis of simulated weed biomass demonstrated that a uniform planting of the crop improved the weed-suppression ability of the crop canopy. Differences in weed suppressiveness between planting patterns were largest with weed emergence before crop emergence, when the suppressive effect of the crop was only marginal. With simultaneous emergence a uniform planting pattern was 8 and 15 % more competitive than a row and a random planting pattern, respectively. When weed emergence occurred after crop emergence, differences between crop planting patterns further decreased as crop canopy closure was reached early on regardless of planting pattern. We furthermore conclude that our modelling approach provides promising avenues to further explore crop-weed interactions and aid in the design of crop management strategies that aim at improving crop competitiveness with weeds. PMID- 27000876 TI - The Rice TCM5 Gene Encoding a Novel Deg Protease Protein is Essential for Chloroplast Development under High Temperatures. AB - BACKGROUND: High temperature affects a broad spectrum of cellular components and metabolism in plants. The Deg/HtrA family of ATP-independent serine endopeptidases is present in nearly all organisms. Deg proteases are required for the survival of Escherichia coli at high temperatures. However, it is still unclear whether rice Deg proteases are required for chloroplast development under high temperatures. RESULTS: In this study, we reported the first rice deg mutant tcm5 (thermo-sensitive chlorophyll-deficient mutant 5) that has an albino phenotype, defective chloroplasts and could not survive after the 4-5 leaf seedling stage when grown at high temperature (32 degrees C). However, when grown at low temperatures (20 degrees C), tcm5 has a normal phenotype. Map-based cloning showed that TCM5 encoding a chloroplast-targeted Deg protease protein. The TCM5 transcripts were highly expressed in all green tissues and undetectable in other tissues, showing the tissue-specific expression. In tcm5 mutants grown at high temperatures, the transcript levels of certain genes associated with chloroplast development especially PSII-associated genes were severely affected, but recovered to normal levels at low temperatures. These results showed important role of TCM5 for chloroplast development under high temperatures. CONCLUSIONS: The TCM5 encodes chloroplast-targeted Deg protease protein which is important for chloroplast development and the maintenance of PSII function and its disruption would lead to a defective chloroplast and affected expression levels of genes associated with chloroplast development and photosynthesis at early rice seedling stage under high temperatures. PMID- 27000877 TI - Guidelines in review: 2015 ACR/ACC/AHA/AATS/ACEP/ASNC/NASCI/SAEM/SCCT/SCMR/SCPC/SNMMI/STR/STS Appropriate Utilization of Cardiovascular Imaging in Emergency Department Patients with Chest Pain: A joint document of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Appropriate Use Criteria Task Force. PMID- 27000878 TI - The use of vasodilator myocardial perfusion imaging in severe aortic stenosis: Is it time for a new prospective study? PMID- 27000879 TI - Using advanced technology to reduce the dose of SPECT MPI radiation. PMID- 27000880 TI - 18F-FDG PET/CT uptake of a nonbacterial thrombotic endocarditis. PMID- 27000881 TI - Translational Hurdles in Stroke Recovery Studies. AB - Emerging understanding of brain plasticity has opened new avenues for the treatment of stroke. The promising preclinical evidence with neuroprotective drugs has not been confirmed in clinical trials, thus nowadays, researchers, pharmaceutical companies, and funding bodies hesitate to initiate these expensive trials with restorative therapies. Since many of the previous failures can be traced to low study quality, a number of guidelines such as STAIR and STEPS were introduced to rectify these shortcomings. However, these guidelines stem from the study design for neuroprotective drugs and one may question whether they are appropriate for restorative approaches, which rely heavily on behavioral testing. Most of the recovery studies conducted in stroke patients have been small-scale, proof-of-concept trials. Consequently, the overall effect sizes of pooled phase II trials have proved unreliable and unstable in most meta-analyses. Although the methodological quality of trials in humans is improving, most studies still suffer from methodological flaws and do not meet even the minimum of evidence based standards for reporting randomized controlled trials. The power problem of most phase II trials is mostly attributable to a lack of proper stratification with robust prognostic factors at baseline as well as the incorrect assumption that all patients will exhibit the same proportional amount of spontaneous neurological recovery poststroke. In addition, most trials suffer from insufficient treatment contrasts between the experimental and control arm and the outcomes have not been sufficiently responsive to detect small but clinically relevant changes in neurological impairments and activities. This narrative review describes the main factors that bias recovery studies, both in experimental animals and stroke patients. PMID- 27000883 TI - Revision with Totally Hand-Sewn Gastrojejunostomy and Vagotomy for Refractory Marginal Ulcer after Laparoscopic Roux-en-Y Gastric Bypass. AB - BACKGROUND: Marginal ulcer is not infrequent after laparoscopic Roux-en-Y gastric bypass and could result in undesirable complications, such as intractability, bleeding, or perforation. Those patients who failed medical therapy, regarded as refractory marginal ulcers, may be considered as candidates for revisional surgery. Herein, we make a video presentation of a laparoscopic revisional procedure for refractory marginal ulcer. METHODS: A 29-year-old morbidly obese woman (initial body mass index 37.1 kg/m(2)), a non-smoker, presented with persistent epigastric pain 3 months after initial laparoscopic Roux-en-Y gastric bypass at another institution. After an exhaustive work-up there, only the gastroendoscopy revealed a marginal ulcer and she underwent medical treatment (proton pump inhibitor and sucralfate) for 3 months, but the patient's symptom aggravated and the serial gastroendoscopies still confirmed the marginal ulcer without obvious resolution after a total of 4 months proton pump inhibitor therapy, suggesting failure of medical treatment and intractability. Laparoscopic revisional procedure with totally hand-sewn gastrojejunostomy and vagotomy was performed to relieve her intractable condition. RESULTS: The procedure took 130 min, without any intra-operative complications. Blood loss was 80 mL. The patient had an uneventful postoperative course, and the postoperative hospital stay was 3 days. She was relieved of her symptoms after this revisional surgery, and a subsequent gastroendoscopy 15 months later showed no marginal ulcers. CONCLUSIONS: Though long-term follow-up is needed to draw a definite conclusion, totally hand-sewn gastrojejunostomy and vagotomy remains a practicable revisional procedure to relieve refractory marginal ulcers. PMID- 27000882 TI - Kaempferol inhibits the production of ROS to modulate OPN-alphavbeta3 integrin pathway in HUVECs. AB - In the present study, we tested the hypothesis that aldosterone regulates osteopontin (OPN)-related signaling pathways to promote nuclear factor kappaB (NF kappaB) activation in primary human umbilical vein endothelial cells (HUVECs) and that kaempferol, a flavonoid compound, blocks those changes. Aldosterone induced productions of reactive oxygen species (ROS), OPN, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) and expression of nicotinamide adenine dinucleotide phosphate-oxidase 4 (Nox4), NF-kappaB, OPN, alphavbeta3 (alphavbeta3) integrin, and inhibitor of NF-kappaB alpha phosphorylation (P IkappaBalpha) in HUVEC. HUVECs were pretreated with kaempferol (0, 1, 3, or 10 MUM) for 1 h and exposed to aldosterone (10(-6) M) for 24 h. Kaempferol reduced ROS, OPN, NF-kappaB, IL-6, and TNF-alpha levels; Nox4, alphavbeta3 integrin; and P-IkappaBalpha expressions. The effect of aldosterone was also abrogated by spironolactone (10(-6) M). In addition, vitamin C (20 mmol/L) reduced ROS production. Vitamin C and LM609 (10 MUg/mL) treatment decreased expressions of OPN, alphavbeta3 integrin, and NF-kappaB (P < 0.05 or P < 0.01). The present results suggest that kaempferol may modulate OPN-alphavbeta3 integrin pathway to inhibit NF-kappaB activation in HUVECs. PMID- 27000884 TI - Lung Tissue Volume is Elevated in Obesity and Reduced by Bariatric Surgery. AB - BACKGROUND: Bariatric surgery (BS) in severely obese subjects causes a significant reduction of body weight with lung function improvement. We have shown that abnormalities in pulmonary gas exchange in morbidly obese subjects are substantially improved with BS. These abnormalities were thought to be related to reduced lung volumes as well as to abnormal endothelial function induced by low grade chronic inflammation linked to perivascular adipose tissue (PVAT). In this study, we used computed tomography (CT) to assess whether BS also caused measurable structural changes in the lung tissue volume (Vtiss) and cross sectional vessel analysis, hypothesizing that these measures could be related to the previously reported lung functional changes. METHODS: This is a post hoc analysis of a previous reported prospective study. Pulmonary vessels and lung volumes, including Vtiss, were quantified in thoracic CT scans. We compared findings in 12 obese women before and after BS and in 8 healthy lean women. RESULTS: Vtiss was significantly elevated in obese subjects before BS compared to control subjects and systematically reduced after BS (by 8 %); other CT lung volumes or vascular areas were not affected in a consistent manner. No relationship was observed between BS-induced individual changes in Vtiss and pulmonary vessel area. CONCLUSIONS: Vtiss is elevated in morbidly obese subjects, compared to lean individuals of similar body height, and is systematically reduced by BS. These effects do not appear related to vascular changes but may be caused by elevated extravascular lung water, due to low-grade inflammation, and/or hypertrophic PVAT in severe obesity. PMID- 27000886 TI - Robotic-assisted oropharyngeal reconstruction. AB - The development of robotic surgery has brought new levels of precision and control to minimally invasive surgical techniques. Its effectiveness, well established in urologic and gynecologic surgery applications, has also been demonstrated in cardiac, endocrine and general surgery. Recently, trans-oral robotic approaches to oropharyngeal tumor resection have been reported and, by eliminating the need for morbid lip and mandible splitting approaches, trans-oral robotic surgery (TORS) has allowed a re-assessment of surgical options for early stage tumors which have until recently been treated primarily with chemoradiation. The application of the TORS approach to malignant and non malignant conditions affecting the oropharynx has created the need to develop robotic-assisted methods of managing the resultant tissue defects and to assess and compare the effectiveness of these procedures. This report details our early experience with the use of robotic surgery for management of soft tissue defects of the oropharynx in 12 patients. PMID- 27000885 TI - Correlation of histomorphologic findings and partial neurovascular bundle preservation during laparoscopic and robotic radical prostatectomy. AB - The objective of this work was to compare the amount of residual periprostatic tissue for radical prostatectomy performed by the partial NS (PNS) technique with that performed by the nerve-sparing (NS) or wide-resection (WR) techniques. Retrospective histomorphologic evaluation of radical prostatectomy specimens (RPSs) from patients undergoing laparoscopic radical prostatectomy (LRP) or robot assisted radical prostatectomy (RARP) was performed. The posterolateral regions corresponding to the neurovascular bundle in RPSs from 48 patients who had undergone NS, PNS, or WR during LRP (n = 30) or RARP (n = 18) were examined by two pathologists unaware of the technique used. The RPSs were evaluated at the base, mid-gland, and apex. The amount of periprostatic tissue at each site was recorded. Measurements were analyzed by use of a linear mixed model. For both LRP and RARP, each gradation of nerve-preservation was associated with periprostatic tissue, except PNS and WR did not differ for LRP at the apex and base or for RARP at the apex, mid-gland, and base. For LRP, a greater amount of tissue was on the left side of the prostate than on the right at the mid-gland level (P = 0.004) whereas for RARP the opposite was found (P = 0.024). Of 18 separate analyses, 13 were significantly associated. The study is limited by its retrospective design. The amount of periprostatic tissue in the neurovascular bundle area correlates well with the nerve-preservation approach used during LRP and RARP, providing anatomic evidence supporting the PNS approach. We also describe a novel finding of laterality bias at the mid-gland level in LRP and RARP specimens. PMID- 27000887 TI - Outcomes of obese versus non-obese subjects undergoing robotic-assisted hysterectomy: a multi-institutional study. AB - The goal of our study was to determine whether there was a difference in operative outcomes in obese versus non-obese subjects undergoing robotic-assisted hysterectomies of varying levels of difficulty. Secondarily, we sought to analyze the published outcomes between robotic-assisted hysterectomy and total laparoscopic hysterectomy in obese women at each of these levels of difficulty. This was a multi-institutional retrospective cohort study of all patients undergoing robotic-assisted hysterectomy by five gynecologic oncologists at four geographically separate locations from April 2003 to March 2008. The cohort was stratified into obese vs. non-obese groups, and defined surgical outcomes compared between groups, then further divided into three subgroups based on case difficulty level. Univariate analysis and regression analysis using SAS 9.1 was performed. We then conducted a literature search of total laparoscopic hysterectomy outcomes in obese women, dividing the resulting studies into three comparative subgroups based on surgical difficulty levels for comparison with our robotic-assisted hysterectomy results. Our cohort had 228 obese and 323 non-obese subjects. Overall, the obese group had higher blood loss and longer operative time. When further stratified by level of difficulty, obese subjects also had a higher average blood loss and longer operative time in the hysterectomy-alone subgroup. No clinically significant differences in operative outcomes exist between obese and non-obese women when utilizing the da Vinci robotic system to perform a hysterectomy, independent of case difficulty level. More prospective, controlled studies which compare the two surgical approaches of robotic-assisted and laparoscopic hysterectomy approaches are needed. PMID- 27000888 TI - Incidence and location of positive surgical margins following open, pure laparoscopic, and robotic-assisted radical prostatectomy and its relation with neurovascular preservation: a single-institution experience. AB - To evaluate whether robotic-assisted radical prostatectomy (dvRP) provides adequate local control of the disease, incidence of positive surgical margins (PSMs) obtained with dvRP was compared with that of laparoscopic radical prostatectomy (LRP) and with that of open radical retropubic prostatectomy (RRP) performed in a single institution by the same surgeons. We also studied whether neurovascular bundle preservation modified PSM rates. The records were retrospectively reviewed from electronic medical data, and three groups of 100 patients were organized. Group 1 included 100 patients who underwent RRP prior to the incorporation of minimally invasive techniques. Group 2 included the first 100 patients who underwent LRP, and group 3 was made up of the first 100 patients who underwent dvRP. All surgical specimens were analyzed by the same pathologist. We used the technique described by Patel et al. for dvRP. LRP was performed using a five-trocar extraperitoneal approach as previously published by the authors. RRP was performed using retrograde dissection as described by Walsh et al. The final decision of preserving neurovascular bundles was made during surgery. Using D'Amico's risk classification, the dvRP group had a lower percentage of patients with low risk (dvRP versus LRP p = 0.017; dvRP versus RRP p = 0.0108). No statistically significant differences were found within high- and intermediate risk groups. A higher percentage of patients with pT3 disease was found in the dvRP group compared with the RRP group (p = 0.0408). There were no statistically significant differences regarding PSMs among groups (RRP: 25, LRP: 14, dvRP: 18), although when we compared the total number of PSMs we found that the dvRP group had 18 PSMs versus 21 and 50 PSMs for LRP and RRP, respectively. All three groups had more PSMs located posterolaterally. There was a higher percentage of nerve sparing procedures in the dvRP group (dvRP: 91 patients, LRP: 47 patients, RRP: 5 patients) (p < 0.0001). No statistically significant differences were found in the PSM rates between the three techniques analyzed. The number of nerve-sparing procedures in the dvRP group was statistically higher. However, this preservation did not modify PSM rates. PMID- 27000889 TI - Learning curves in expert and non-expert laparoscopic surgeons for robotic suturing with the da Vinci((r)) Surgical System. AB - We investigated learning curves for robotic suturing of expert and non-expert laparoscopic surgeons to explore the length of time required to reach an acceptable plateau of technical skills. Laparoscopic suturing skills were evaluated in a training box with conventional laparoscopic instrumentation in phase 1. In phase 2, robotic suturing skills were evaluated during a training program on non-surviving animals by analyzing time required for five intracorporal stitches on the small bowel. Learning curves were plotted. A significant difference in technical skills between the expert and non-expert surgeons was demonstrated in phase 1 and at the beginning of phase 2. Both surgeons reached a learning-curve plateau exhibiting similar robotic suturing skills at the end of 90 min of training. Skills were subsequently retained equally by both surgeons. Short duration of training was sufficient for the non expert laparoscopic surgeon to match the robotic suturing performance of the expert laparoscopic surgeon. PMID- 27000890 TI - Subjective and objective outcomes 1 year after robotic-assisted laparoscopic sacrocolpopexy. AB - We aimed to assess the subjective and objective outcomes 1 year after robotic sacrocolpopexy using a type I polypropylene mesh. This was a case series of 64 patients who underwent a robotic-assisted laparoscopic sacrocolpopexy using a type I monofilament polypropylene mesh coated with hydrophilic porcine collagen. Objective and subjective outcomes were assessed using the pelvic organ prolapse quantification (POP-Q), the short forms of the Pelvic Floor Impact Questionnaire (PFIQ 7) and the Pelvic Floor Distress Inventory (PFDI-20). Outcome measures were collected pre-operatively and 1 year post-operatively on all but one patient, who was lost to follow-up. Paired comparisons between pre- and post-operative outcomes were performed using the Wilcoxon signed rank test. At 1 year, POP-Q stage II or greater and loss of follow-up were considered to be surgical failure. The "surgical cure" rate was 89%. We observed three distal anterior failures, two distal posterior failures and one apical failure, and one patient was lost to follow-up. We found significant differences between pre- and post-operative POP-Q measurements (p < 0.001) and PFDI-20/PFIQ-7 total scores (p < 0.001). Robotic sacrocolpopexy using this polypropylene mesh resulted in significant improvements in subjective and objective outcome measures at 1 year. PMID- 27000891 TI - Comparative analysis of vaginal versus robotic-assisted hysterectomy for benign indications. AB - We aimed to compare perioperative outcomes of robotic-assisted hysterectomy versus vaginal hysterectomy in patients with benign gynecologic conditions, using a retrospective chart review of 240 consecutive benign hysterectomies from May 2008 to April of 2010 performed by a single surgical team at the Eisenhower Medical Center. The analysis included an equal number of cases in each group: 120 robotic-assisted total laparoscopic hysterectomies and 120 total vaginal hysterectomies. Consecutive cases met the inclusion criteria of benign disease. There were no statistically significant differences related to age, body mass index, history of prior abdominal surgery, or uterine weight. Operative times in the robotic group were significantly longer by an average of 59 min (p < 0.001). Patients with robotic-assisted hysterectomy had clinically equivalent estimated blood loss (55.5 ml vs. 84.7 ml, p < 0.001) and the intraoperative complication rates were 1.7% vaginal versus 0% robotic (p = 0.156). There was one conversion in the vaginal group due to pelvic adhesions and no conversions in the robotic group. Length of hospital stay was 1 day for both groups. The perioperative complication rates were equivalent between groups (6.7 vs. 11.7%, p = 0.180), but there were more major complications in the vaginal group (0 vs. 3.3%, p = 0.044). We conclude that, in a comparable group of patients, robotic-assisted hysterectomy takes longer to complete but results in fewer major complications. PMID- 27000892 TI - Robotic assisted radical prostatectomy in morbidly obese patients: how to create a cost-effective adequate optical trocar. AB - Obesity is a major health issue in modern society, and with the progressive widespread employment of robotic assisted radical prostatectomy (RALP), the urologist-robotic surgeon is increasingly involved in the treatment of obese patients. However, the vast majority of urological departments are not equipped with a complete set of bariatric instruments. One of the potential difficulties of robotic surgery on the morbidly obese patient is the relatively short length of the optical trocar sheath, as the optical robotic arm requires some very valuable centimeters of the sheath to hang onto. This condition may make it impossible to properly reach the peritoneal cavity with the optical trocar during the RALP procedure. We present a series of four morbidly obese patients (BMI ranging from 42.1 to 46.2) with localized prostate cancer treated with RALP. We have developed an effective and "easy-to-implement" solution to the problem of properly elongating the sheath of the optical trocar which involves the use of the plastic cylindrical transparent protective tube of a disposable 26-Ch Amplatz sheath. The Amplatz sheath, with an internal diameter of 13 mm and length of 25 cm, perfectly fits outside of the 13-mm trocar usually employed for the optical trocar. Additionally, the cylindrical tube perfectly fits and hangs onto the robotic optical arm system. Mean operative time was 202.5 min (range 185-220 min). Mean blood loss was 284 mL (range 185-380 mL). Catheterization time and hospital stay were 5 and 6 days, respectively, in all patients. All procedures were safely completed, and no minor or major complications were reported. The optical trocar lengthening technique allowed us to properly perform RALP procedures even in severely morbidly obese patients in an urological setting not equipped for bariatric minimally invasive surgery. PMID- 27000893 TI - Measurements of the contact force from myenteric contractions on a solid bolus. AB - The development of robotic capsule endoscopes (RCEs) is one avenue presently investigated by multiple research groups to minimize invasiveness and enhance outcomes of enteroscopic procedures. Understanding the biomechanical response of the small bowel to RCEs is needed for design optimization of these devices. In previous work, the authors developed, characterized, and tested the migrating motor complex force sensor (MFS), a novel sensor for quantifying the contact forces per unit of axial length exerted by the myenteron on a solid bolus. This work is a continuation, in which the MFS is used to quantify the contractile strength in the small intestine proximal, middle, and distal regions of five live porcine models. The MFSs are surgically implanted in a generally anesthetized animal, and force data from 5 min of dwell time are analyzed. The mean myenteric contact force from all porcine models and locations within the bowel is 1.9 +/- 1.0 N cm(-1). Examining the results based on the small bowel region shows a statistically significant strengthening trend in the contractile force from proximal to middle to distal with mean forces of 1.2 +/- 0.5, 1.9 +/- 0.9, and 2.3 +/- 1.0 N cm(-1), respectively (mean +/- one standard deviation). Quantification of the contact force against a solid bolus provides developers of RCEs with a valuable, experimentally derived parameter of the intraluminal environment. PMID- 27000894 TI - Reproductive outcomes following robotic-assisted laparoscopic myomectomy (RALM). AB - Uterine myomas are the most common type of benign tumor in women of reproductive age and are commonly associated with menorrhagia, dysmenorrhea, dyspareunia, and urinary symptoms. Uterine fibroids have been also linked to infertility and pregnancy loss. Women wishing to preserve or restore their fertility are best treated by myomectomy. Robotic-assisted laparoscopic myomectomy is one of the latest technological applications of minimally invasive surgery. Limited data exist regarding the feasibility of robotic-assisted laparoscopic myomectomy (RALM) in terms of pregnancy and surgical outcomes, and more studies are needed. The goal of this study is to assess reproductive outcomes following RALM in a private practice setting. The study was performed in the form of a retrospective chart review. Female patients 22-44 years old diagnosed with intramural myoma were eligible for inclusion. Presence of a myoma was a necessary but not necessarily the presenting symptom. All patients underwent RALM between January 2006 and May 2009 under the care of one surgeon at two clinical sites. Patients were selected postsurgically via chart review based on inclusion parameters outlined above. Median values for pregnancy rate, number of myomas, diameter of largest myoma, surgery duration, and blood loss were calculated and used for subsequent statistical analysis. Clinically useful markers for pregnancy outcomes evaluation following RALM were identified. Thirty patients were enrolled, of whom 16 were interested in conception due to infertility. A pregnancy rate of 75 % was recorded. Among those who conceived, eight patients (67 %) reported natural conception within 6 months of unprotected intercourse, while four patients (33 %) utilized assisted reproductive technologies to conceive. One patient (8 %) miscarried. Two patients (17 %) experienced premature delivery, at 28 and 32 weeks, respectively. All deliveries were performed via Cesarean section. No surgical complications were reported following RALM. There were no cases of scar dehiscence or rupture. The median number of myomas in those who delivered was estimated at 1.0 compared with 3.5 in those unable to conceive (p < 0.05). In addition, median age was 34 compared with 42.5 years, respectively (p < 0.05). This retrospective study assessed pregnancy outcomes following RALM. Our pregnancy rate of 75 % combined with a low incidence of complications contributes to the limited pool of data available on this topic, and supports the need for a multicenter trial to further evaluate effectiveness and safety of RALM in terms of pregnancy outcomes. PMID- 27000895 TI - Initial experiences with RoSS surgical simulator in residency training: a validity and model analysis. AB - Robotic surgery is an important new tool in many surgical procedures, and training curriculums must adapt to this new technology. Robotic surgical simulators have been developed as a means of providing training without the inherent risks of actual surgery. The purpose of this study is to evaluate the construct validity of the RoSS surgical simulator by correlating simulator performance with amount of time in training and to create a performance model in which time in training is a parameter. A total of eight residents with varying amounts of training were given access to the RoSS surgical simulator and were evaluated on performance of a simulated surgical task. This data was then used to create Akaike information criteria to compare goodness of fit. Participants were also given a questionnaire as to their experience with the simulator and their feelings about the use of simulators in training. Training time and performance within the simulator were shown to have a linear relationship. Correlations were high, with R (2) values of 0.95, 0.94, and 0.86 for each of the three performance metrics. Likelihood ratios were similarly high at 4.25 * 10(9), 10,950, and 362. Participant opinion showed that residents feel that robotic training is an important part of their education and that the simulator is an effective supplement. The RoSS surgical simulator accurately corresponds to training level and is a valid evaluation tool of training experience. These findings are encouraging for the use of robotic simulators in surgical training. PMID- 27000896 TI - Using the "Summa Set-up" in robotic assisted gynecologic surgery. AB - During challenging gynecologic (GYN) procedures, the conventional robotic set-up can limit a surgeon's ability to effectively and efficiently perform these procedures. We present a novel set-up using a parallel-docking approach of the da Vinci ((r)) Surgical System with only three robotic arms and incorporating two patient side assist ports to overcome the difficulties presented during challenging GYN procedures. The Summa Set-up (SS) uses 4 ports actively, 2 assist ports and 2 robotic ports, compared to the traditional set-up which uses 4 ports: 1 assist port and 3 robotic ports. With the SS format, the patient-side assistant stands at the head of the bed and can simultaneously retract the uterus and aide in surgical dissection along with the console surgeon. While there are many possibilities of da Vinci ((r)) docking, port placement and assistant placement during robotic-assisted GYN surgery, we believe the SS can be an alternative for many GYN surgeons, especially those in teaching hospitals, for increased mobility and efficiency during complex GYN procedures. PMID- 27000897 TI - Ureteral transection repaired during robot-assisted surgery. AB - During robot-assisted surgery for endometrial cancer, a ureteral injury occurred in two women. Both injuries were repaired successfully with robot-assisted surgery. One of the injuries and its repair are shown in an edited video clip. Ureteral injury is a known complication of gynecologic surgery (Hoffman in OBG Manag 20:16-28, 2008). Transection of the pelvic ureter proximal to the parametrium may be repaired by reapproximation or reimplantation. Robot-assisted surgery has recently been established as useful for the performance of ureteral surgery (Kasturi et al. in Urology 79:680-683, 2012; Rehman et al. in Can J Urol 18:5548-5556, 2011; Patil et al. in Urology 72:47-50, 2008). PMID- 27000898 TI - Transoral robotic resection of an ectopic tongue-base thyroid gland. AB - Lingual thyroid is an uncommon condition, often asymptomatic. Given its benign nature, every treatment should be well balanced in terms of advantages and local morbidity. When a treatment is planned, medical and surgical therapy should be weighed against each other. Among surgical options, robotic techniques offer several advantages compared to traditional transoral procedures and external approaches, in terms of ability of resection, morbidity and quality of life. Here we present the case of a patient with tongue-base ectopic thyroid managed by means of transoral robotic surgery. The intuitiveness of the procedure associated with very minimal invasiveness are confirmed in this case. Particularly when dealing with benign lesions that involve hard-to-reach regions such as the tongue base, robotic techniques should be considered as a truly valid alternative to traditional techniques. PMID- 27000899 TI - Trans-oral robotic submandibular gland removal. AB - Submandibular gland excision is traditionally performed via a trans-cervical approach. While generally regarded as a relatively simple surgical procedure, several complications are possible, including injury to the marginal mandibular branch of the facial nerve, lingual nerve, hypoglossal nerve, facial artery and a visible unsightly neck scar or keloid. The trans-oral route has the ability to eliminate a cervical scar and decrease risk of injury to several structures. Coincident with the development of the trans-oral approach, robotic surgery has been gaining popularity in the operative management of early oral cavity, tonsil, and tongue base malignancies. A 51-year-old female presented to our institution with a 15-year history of recurrent left submandibular gland sialoadenitis. She previously underwent a rhytidectomy with cervicoplasty and was interested in a trans-oral approach to avoid a neck incision. Here we present a novel application of the da Vinci Surgical Robot for trans-oral removal of the submandibular gland. PMID- 27000900 TI - Robot-assisted whipple's operation for solid pseudopapillary tumour of pancreas. AB - Solid pseudopapillary tumor is a rare tumor of the pancreas. They are slow growing with low malignant potential. The prognosis is excellent after surgical resection. Here we report a case of solid pseudopapillary tumor of the pancreas at the uncinate process. There are increasing interests about minimal access surgery for pancreatic lesion. However conventional laparoscopic Whipple's operation is technically difficult. With the benign characteristic of this tumor, as well as the advance in robotic surgery, robot assisted approach is an ideal alternative for this case. The operation was performed with a five-port approach with the use of da Vinci S Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). The operative time was 420 min and operative blood loss was 100 ml. The post operative course was uneventful and the patient was discharged on post operative day 10. This case demonstrates the feasibility of robot assisted Whipple's operation, which has not been extensively reported in the literature. PMID- 27000901 TI - Laparoscopic versus robotic right colectomy: a single surgeon's experience. AB - There is increased interest in robotic techniques for colon resection, but the role of robotics in colorectal surgery has not yet been defined. The purpose of this study was to compare our recent experience with robotic right colectomy to that with laparoscopic right colectomy. From November 2008 to June 2011, a total of 47 consecutive patients underwent elective, right colectomy: 25 laparoscopic right colectomies (LRC) and 22 robotic right colectomies (RRC). All procedures in this study were performed by a single, board-certified colon and rectal surgeon (H.J.L.). Main outcomes recorded included conversion rate, operative time (OT), estimated blood loss (EBL), length of extraction sites, length of stay (LOS), and complications. Data studied were prospectively recorded in a database and were retrospectively reviewed. Mean OT for LRC was 107 +/- 36.7 min (median 98, range 48-207) and for RRC was 189.1 +/- 38.1 min (median 185, range 123-288, P < 0.001). Mean total operating room time (TORT) for LRC was 158.6 +/- 38.1 min (median 149, range 104-274) and for RRC was 258.3 +/- 40.9 (median 251, range 182 372, P < 0.001). The tendency lines for both OT and TORT decreased over time for RRC. EBL for LRC was 70.2 +/- 52.9 ml (median 50, range 10-200) and for RRC was 60.8 +/- 71.3 ml (median 40, range 10-300, P = 0.037). The mean extraction site length for the laparoscopic group was 5.3 +/- 1.3 cm (median 5, range 4-11) and for the robotic group was 4.6 +/- 0.7 cm (median 4.5, range 3.5-6, p = 0.008). LOS was similar for both groups, as were complications. No cases were converted to open. No leaks occurred and there was no 30-day mortality. RRC is safe and feasible, with similar outcomes to LRC. Operative times were longer for RRC; however, they compare favorably with times for LRC published in the literature. Extraction site length and EBL were less for RRC. However, further study is necessary to demonstrate the clinical relevance of these findings. We are optimistic that OT and TORT will continue to improve. PMID- 27000902 TI - An interactive method for achieving ergonomically optimum conditions during laparoscopic surgery. AB - Laparoscopy is widely used during living kidney donation, nephrectomy, bariatric surgery, and surgery for gastrointestinal tumors and colorectal cancer. However, laparoscopic surgery requires prolonged use of instruments and has low mechanical efficiency. In addition, to meet specific surgical demands while visualizing the surgical area on the screen, surgical personnel frequently violate the postures proposed by human factor engineering; this naturally results in a physical burden on the personnel. In this study, using laparoscopic nephrectomy as an example, an auxiliary hoisting device for surgery was designed, and pedals from a variety of equipment were integrated into the auxiliary plant. Both entity testing conducted in the hospital and 3D surgical simulation of the auxiliary plant showed that this device could improve compliance with human factor engineering recommendations during laparoscopic surgery and could also promote interaction and tacit understanding between surgical personnel, thereby providing ergonomically optimum conditions during laparoscopy. PMID- 27000903 TI - Survey of minimally invasive general surgery fellows training in robotic surgery. AB - Minimally invasive surgery fellowships offer experience in robotic surgery, the nature of which is poorly defined. The objective of this survey was to determine the current status and opportunities for robotic surgery training available to fellows training in the United States and Canada. Sixty-five minimally invasive surgery fellows, attending a fundamentals of fellowship conference, were asked to complete a questionnaire regarding their demographics and experiences with robotic surgery and training. Fifty-one of the surveyed fellows completed the questionnaire (83 % response). Seventy-two percent of respondents had staff surgeons trained in performing robotic procedures, with 55 % of respondents having general surgery procedures performed robotically at their institution. Just over half (53 %) had access to a simulation facility for robotic training. Thirty-three percent offered mechanisms for certification and 11 % offered fellowships in robotic surgery. One-third of the minimally invasive surgery fellows felt they had been trained in robotic surgery and would consider making it part of their practice after fellowship. However, most (80 %) had no plans to pursue robotic surgery fellowships. Although a large group (63 %) felt optimistic about the future of robotic surgery, most respondents (72.5 %) felt their current experience with robotic surgery training was poor or below average. There is wide variation in exposure to and training in robotic surgery in minimally invasive surgery fellowship programs in the United States and Canada. Although a third of trainees felt adequately trained for performing robotic procedures, most fellows felt that their current experience with training was not adequate. PMID- 27000904 TI - Robot-assisted single-incision laparoscopic myomectomy: initial report and technique. AB - Single-incision laparoscopic surgery for gynecologic applications has recently been described. Such an ultra-minimally invasive technique is attractive to patients and may have clinical advantages because of the reduced number of abdominal incisions. However, because of its extreme geometrical challenges and instrument crowding, single-incision laparoscopy is such a major deviation from optimum surgical ergonomics that it is unlikely to gain popularity. Robot assistance in single-incision laparoscopy has recently been described for some ablative gynecologic procedures, and it seems to have technical advantages. However, no suture-intensive applications of this technique have yet been reported. We describe our initial experience with robot-assisted single-incision laparoscopic myomectomy and provide essential technical detail to enable successful replication of this technique in the context of an advanced robotic surgical team. PMID- 27000905 TI - Robot-assisted laparoscopic prostatectomy and previous surgical history: a multidisciplinary approach. AB - Previous abdominal or prostate surgery can be a significant barrier to subsequent minimally invasive procedures, including radical prostatectomy (RP). This is relevant to a quarter of prostatectomy patients who have had previous surgery. The technological advances of robot-assisted laparoscopic RP (RALP) can mitigate some of these challenges. To that end, our objective was to elucidate the effect of previous surgery on RALP, and to describe a multidisciplinary approach to the previously entered abdomen. One-thousand four-hundred and fourteen RALP patients were identified from a single-surgeon database. Potentially difficult cases were discussed preoperatively and treated in a multidisciplinary fashion with a general surgeon. Operative, pathological, and functional outcomes were analyzed after stratification by previous surgical history. Four-hundred and twenty (30 %) patients underwent previous surgery at least once. Perioperative outcomes were similar among most groups. Previous major abdominal surgery was associated with increased operative time (147 vs. 119 min, p < 0.001), as was the presence of adhesions (120 vs. 154 min, p < 0.001). Incidence of complications was comparable, irrespective of surgical history. Major complications included two enterotomies diagnosed intraoperatively and one patient requiring reoperation. All cases were performed robotically, without conversion to open-RP. There was no difference in biochemical disease-free survival among surgical groups and continence and potency were equivalent between groups. In conclusion, previous abdominal surgery did not affect the safety or feasibility of RALP, with all patients experiencing comparable perioperative, functional, and oncologic outcomes. PMID- 27000906 TI - The effect of a silicone-coated robotic needle holder. AB - We have evaluated a silicone-coated robotic needle holder. We measured the intensity and extension of a 7-0 Prolene suture after holding it with a robotic instrument. To prevent damage, we modified it by coating the jaws with silicone. In the first study there were four groups: Group C, suture not held by instruments (n = 6); Group R, suture held by a robotic instrument (n = 6); Group SO, suture held by a robotic instrument with one jaw coated with silicone (n = 6); and Group SB, suture held by a robotic instrument with both jaws coated with silicone (n = 6). Finally, one instrument with a single jaw coated with silicone and one with both jaws coated with silicone were tested to evaluate their manipulation capabilities. The intensity and extension of sutures in groups C, R, SO, and SB were 3.05 N/37.9 %, 2.28 N/23.9 %, 3.06 N/37.5 %, and 2.96 N/36.2 %, respectively. We also found that the grip force of the instrument with both jaws coated with silicone was low, which caused the needle to be unstable or to turn, resulting in poor suturing. Manipulation of the instrument with one jaw coated with silicone was satisfactory. It is concluded that the best way to avoid breaking small synthetic monofilament sutures is not to use the robotic needle holder; the holder can be used, however, if one jaw only is coated with silicone. PMID- 27000907 TI - Robot-assisted laparoscopic myomectomy and adenomyomectomy with a flexible CO2 laser device. AB - We describe a novel surgical technique combining the use of a robotic surgical platform with a flexible CO2 laser in gynecologic surgery at a university hospital-based reproductive medicine practice. Thirteen women with symptomatic uterine fibroids and/or adenomyosis, desiring uterine conservation, underwent robot-assisted laparoscopic myomectomy or focal adenomyomectomy with CO2 laser energy using a novel flexible delivery fiber (BeamPath GYN-L fiber, OmniGuide, Cambridge, MA, USA). On average, four myomas or areas of adenomyosis were removed with an average total specimen weight of 95 g. The average operating time was 169 min and the average estimated blood loss was 25 mL. No perioperative complications were observed. Preliminary experience with robot-assisted minimally invasive gynecologic surgery utilizing a novel flexible CO2 laser fiber has comparable operative outcomes to those reported for conventional laparoscopic energy sources, and this technique appears safe. The minimal lateral thermal spread of photonic energy, combined with the enhanced precision allowed by a computer-based surgical platform, appears ideal for reproductive surgical applications. PMID- 27000908 TI - Retrospective analysis of robot-assisted versus standard laparoscopy in the treatment of pelvic pain indicative of endometriosis. AB - We examined the feasibility of treating pelvic pain in patients with suspected endometriosis using robot-assisted laparoscopic techniques compared with CO2 laser laparoscopy, in a retrospective review from a single surgeon's practice, including the last 100 standard laparoscopic (December 2004-September 2007) and the first 180 robot-assisted (July 2007-January 2010) surgeries to treat suspected endometriosis. Perioperative outcomes and postoperative pain were compared by technique. Patients in each group were comparable in gravidity, body mass index, prior endometriosis, prior abdominopelvic surgery, American Fertility Society stage, and biopsy rates. Operative time (77 vs. 72 min), blood loss (29 vs. 25 mL), and complication rates (1.1 vs. 0 %) in robot-assisted and standard laparoscopy were low and similar for both approaches. Differences were apparent in biopsies confirming endometriosis (80 % robot-assisted vs. 56.8 % traditional laparoscopy, p < 0.001). Most patients reported improved postoperative pain at the first follow-up visit with no differences between the surgical approaches (85 % vs. 80 %, p = 0.365). Perioperative outcomes with robot-assisted surgery were comparable to outcomes using CO2 laser laparoscopy. Further investigation is needed to ascertain whether robotics provides better visual acuity and excision of endometriosis, as suggested by these data, and if long-term resolution of symptoms and fertility outcomes differ by surgical approach. PMID- 27000909 TI - Establishment of a new robotic prostatectomy program at a tertiary Veteran's Affairs medical center. AB - The objective of this study is to report the initial results of a newly established robotic prostatectomy (DVP) program at a Veteran's Affairs (VA) medical center. All patients who underwent a radical prostatectomy during the first 18 months of our robotic surgical program were included in this study. These patients were compared to a control group that included all patients who underwent an open prostatectomy 18 months prior to starting our robotic program. Preoperative, intraoperative and postoperative data was compared between open and robotic prostatectomies. 38 men underwent radical retropubic prostatectomy (RRP) between September 2007 and February 2009. With the introduction of robotic prostatectomy, the total number of prostatectomies increased by 84 % to 70 (9 RRP, 61 DVP). Prostate-specific antigen (PSA), Gleason score and clinical stage were similar for both groups. Average estimated blood loss (EBL) was 1205 mL for RRP and 126 mL for DVP. Mean operative times in minutes were 259 and 254 for RRP and DVP, respectively. Complications included two rectal perforations, a cerebrovascular accident, one death after RRP and one open conversion for failure to progress. Average length of stay was 5.1 for RRP and 1.8 days for DVP. Total positive margins were 24 % for RRP and 15 % for DVP. For T2-specific disease, 16.7 % had positive margins after RRP compared to 4.3 % after DVP. The establishment of a robotic prostatectomy program at a tertiary VA medical center was achieved in a safe and efficient manner with improvement in EBL and length of stay when compared to our open prostatectomies. Oncologic outcomes were equivalent when compared to other initial DVP programs. PMID- 27000910 TI - Technique and surgical outcomes of robot-assisted anterior lumbar interbody fusion. AB - The goal of the study was to determine the effectiveness and safety of a novel technique in which the da Vinci S Surgical Robot (Intuitive Surgical Inc., Sunnyvale, CA, USA) was used in the dissection of the ventral lumbar spine to assist with anterior lumbar interbody fusion (R-ALIF). We performed a retrospective chart review of 11 patients who underwent R-ALIF between 2009 and 2010 at our institution. Due to variations in the surgical technique, the data were separated into three patient groups according to which disc level was operated on: L5-S1 (five patients), L4-L5 (two patients), and combined L4-L5 and L5-S1 (four patients). All patients showed radiographic evidence of fusion, and none of the procedures were converted to open. There were no intraoperative vascular complications, and no postoperative transfusions or ileus. This study shows the feasibility and safety of R-ALIF at L5-S1, L4-L5, and L4-L5 and L5-S1. PMID- 27000911 TI - Does hospital setting post robotic fellowship training affect outcomes? A multi institutional comparison of initial outcomes between academic and community settings. AB - The effect of practice setting on skill development post robotic fellowship training is currently unknown. We sought to compare learning curves between a high-volume academic center and a similar volume community hospital, in the setting of building a new robotic prostatectomy program. In addition, we sought to characterize benchmarks for learning curve development for post-fellowship training in robotic surgery. At two institutions, one academic (AC) and the other in the community (CO), the first 150 patients who underwent robotic laparoscopic prostatectomy over a period of 1 year were evaluated. We compared the following outcomes, operative time (OT), estimated blood loss (EBL), and positive surgical margin (PSM) rates, by two surgeons. Both surgeons completed the same surgical robotic fellowship in the same year. Cases were divided by tertile and primary outcomes measures were compared. Demographic data were similar between the two groups. Statistical differences were seen in age, preoperative Sexual Health Inventory for Men score, clinical and pathologic stage, and bladder neck reconstruction rate (p < 0.05). Overall, there was no significant difference in OT between AC (174 min) and CO (181 min) (p = 0.1099). Both EBL and PSM were lower in the AC (155 vs. 197 ml, p < 0.001 and 10 vs. 26 %, p < 0.05). The difference in OT was significant only in the first tertile of cases (AC 168 min vs. CO 193 min, p = 0.002). However, OT increased by 13 min in AC and decreased by 22 min in CO, when comparing the first and last tertile. EBL was different between AC (161ml) and CO (212 ml) only in the first tertile of cases (p = 0.002). Both AC and CO had increased EBL over the last tertile of cases (16.2 vs. 26.5 ml, respectively). These results demonstrate minor differences in outcomes between the two practice settings. Fellowship training in robotic surgery demonstrates a shorter learning curve towards achieving proficiency. Larger and longer term series will be required to assess functional outcomes and time to proficiency. PMID- 27000912 TI - A novel method of bladder neck imbrication to improve early urinary continence following robotic-assisted radical prostatectomy. AB - Early return of continence forms an important component of quality of life for patients after robotic-assisted radical prostatectomy (RALP). Here we describe the steps of bladder neck imbrication and vesico-urethral anastomosis improving early continence after RALP. Between April 2008 and July 2009, 202 consecutive patients underwent RALP for clinically localised prostate cancer in a tertiary referral centre by a single surgeon. One hundred and thirty-two (65 %) of these patients agreed to participate in the study. Prior to November 2008, 51 patients underwent standard RALP as described by Patel et al. From November 2008, 81 patients underwent a novel method of bladder neck imbrication. The robotic urethro-vesical anastomosis commences on the posterior wall of the urethra and proceeds anteriorly. In our technique the anastomosis is halted with the suture arms fixed to the anterior abdominal wall. A new suture is used to perform a two layer repair, anchoring proximally then continuing anteriorly to the level of the urethral stump, where it returns upon itself. The aim is to narrow the urethra to 16 Fr and tighten the second layer to create an imbrication effect. Posterior reconstruction was performed in all patients. Outcome measures were recorded prospectively using the Expanded Prostate Cancer Index Composite tool. Our technique shows significant improvement at all stages of follow-up in urinary summary and incontinence scores. Absolute continence rates increased from 8.2 to 20.5 %, 26.7 to 44.3 %, and 47.7 to 62.3 % at 1.5, 3 and 6 months, respectively. These results support the use of our technique in patients undergoing RALP. PMID- 27000913 TI - Peritoneal dissemination of prostate cancer with the absence of lymph node, skeletal, or visceral metastases in a patient scheduled to undergo robot-assisted radical prostatectomy. AB - Peritoneal dissemination of prostate cancer (PCa) with the absence of other metastases is extremely rare. Atypical sites of metastatic disease, for example the peritoneum, are only a recognized finding at autopsy. Herein, we report a case of peritoneal dissemination of a PCa, with the absence of lymph node, skeletal, or visceral metastases in a patient scheduled to undergo robot-assisted laparoscopic prostatectomy. PMID- 27000914 TI - Robotic-assisted resection of isolated paraaortic lymph node recurrence with right lateral decubitus position. AB - In this report we describe transperitoneal robotic-assisted paraaortic lymphadenectomy via the right lateral decubitus position to treat solitary recurrence in a patient with cervical carcinoma. This is, to our knowledge, the first report utilizing the right lateral decubitus position rather than the traditional approach with the Trendelenberg position. This approach adds another option for surgical approaches to the paraaortic lymph nodes, particularly in subgroups of patients who have significant cardiopulmonary cormobidities and are unable to tolerate the steep Trendelenburg position. PMID- 27000916 TI - Per aspera ad astra (Through hardship to the stars). PMID- 27000915 TI - Internal mammary silicone lymphadenopathy diagnosed by robotic thoracoscopic lymphadenectomy. AB - Internal mammary lymphadenopathy can be caused by a variety of disease processes and is a difficult diagnostic dilemma. We report a case of internal mammary lymphadenopathy, in a patient with a significant history of malignancy, requiring a tissue diagnosis. Robotic thoracoscopic lymphadenectomy was used to facilitate excisional biopsy. Pathology was significant for silicone granulomatous lymphadenitis secondary to silicone breast implants inserted after mastectomy for breast cancer. PMID- 27000917 TI - A special issue on selected papers from the 5th Hamlyn Symposium on Medical Robotics, 2012. PMID- 27000918 TI - Robotic control of a traditional flexible endoscope for therapy. AB - In therapeutic flexible endoscopy a team of physician and assistant(s) is required to control all independent translations and rotations of the flexible endoscope and its instruments. As a consequence the physician lacks valuable force feedback information on tissue interaction, communication errors easily occur, and procedures are not cost-effective. Current tools are not suitable for performing therapeutic procedures in an intuitive and user-friendly way by one person. A shift from more invasive surgical procedures that require external incisions to endoluminal procedures that use the natural body openings could be expected if enabling techniques were available. This paper describes the design and evaluation of a robotic system which interacts with traditional flexible endoscopes to perform therapeutic procedures that require advanced maneuverability. The physician uses one multi-degree-of-freedom input device to control camera steering as well as shaft manipulation of the motorized flexible endoscope, while the other hand is able to manipulate instruments. We identified critical use aspects that need to be addressed in the robotic setup. A proof-of principle setup was built and evaluated to judge the usability of our system. Results show that robotic endoscope control increases efficiency and satisfaction. Participants valued its intuitiveness, its accuracy, the feeling of being in control, and its single-person setup. Future work will concentrate on the design of a system that is fully functional and takes safety, cleanability, and easy positioning close to the patient into account. PMID- 27000919 TI - Lessons learned using the insertable robotic effector platform (IREP) for single port access surgery. AB - This paper presents the preliminary evaluation of a robotic system for single port access surgery. This system may be deployed through a 15-mm incision. It deploys two surgical arms and a third arm manipulating a stereo-vision module that tracks instrument location. The paper presents the design of the robot along with experiments demonstrating the capabilities of this robot. The evaluation includes use of tasks from fundamentals of laparoscopic surgery, evaluation of telemanipulation accuracy, knot tying, and vision tracking of tools. PMID- 27000920 TI - Evaluation of robotic minimally invasive surgical skills using motion studies. AB - Robotic Minimally Invasive Surgery, and the engendered computer-integration, offers unique opportunities for quantitative computer-based surgical-performance evaluation. In this work, we examine extension of traditional manipulative skill assessment, having deep roots in performance evaluation in manufacturing industries, for applicability to robotic surgical skill evaluation. This method relies on: defining task-level segmentation of modular sub-tasks/micro-motions called 'Therbligs' that can be combined to perform a given task; and analyzing intra- and inter-user performance variance by studying surgeons' performance over each 'Therbligs'. Any of the performance metrics of macro-motions-from motion economy, tool motion measurements to handed-symmetry-can now be extended over the micro-motion temporal segments. Evaluation studies were based on video recordings of surgical tasks in two settings: first, we examined performance of two representative manipulation exercises (peg board and pick-and-place) on a da Vinci surgical SKILLS simulator. This affords a relatively-controlled and standardized test-scenarios for surgeons with varied experience-levels. Second, task-sequences from real surgical videos were analyzed with a list of predefined 'Therbligs' in order to investigate its overall usefulness. PMID- 27000922 TI - Preventing slide in Trendelenburg position: randomized trial comparing foam and gel pads. AB - To compare patient slide in Trendelenburg position using egg-crate foam or gel pad. This randomized trial compared slide on friction pads during Trendelenburg position for robotic and laparoscopic gynecologic procedures in 61 patients at the Mayo Clinic Florida between March 11, 2010 and May 31, 2011. Data was analyzed using Student's t test with significance defined as p <= 0.05. There was no significant difference in mean slide according to pad type (foam 3.0 +/- SD 2.1 cm; gel 4.5 +/- SD 4.0 cm, p = 0.08). Minor complaints occurred in 10 % of patients, and did not differ by group (p = 0.4). Most complaints (98 %) were transient shoulder or neck pain. A single patient had both transient right hand numbness and right lateral thigh paresthesia. We assessed outcomes by chart review from the inpatient care and postoperative evaluation notes (mean 44 +/- SD 17 days), and by review of any intervening notes that occurred before the study's end (mean 345 +/- SD 116 days). Trendelenburg-related slide is equivalent on either egg-crate foam or gel pad. PMID- 27000921 TI - Robotically-assisted laparoscopic biliopancreatic diversion with duodenal switch: the utility of the robotic system in bariatric surgery. AB - Biliopancreatic diversion with duodenal switch (BPD/DS) is considered the most effective surgical option for morbidly obese patients. Several techniques have been described: open, laparoscopic, and the combination of open and laparoscopic. Only a few centers in the world perform robotically-assisted laparoscopic BPD/DS and the published literature is limited. We describe our experience using this technique as a safe alternative for treatment of morbid obesity. A review of a prospectively maintained database from 2008 to 2011 was conducted. A total of 107 consecutive patients (F:M = 83:24) were included in this series. Average age was 44.76 years (range 20-67), body mass index 49.97 kg/m(2) (range 37-70), and the number of preoperative comorbidities was 6.24 (range 3-11). The mean operative time for a typical BPD/DS with or without an appendectomy was 264 min (range 192 413), which increased to 298 min (range 210-463) when lysis of adhesion or additional procedures were performed. All study cases were completed using a minimally invasive approach. There were no intraoperative or 30-day major postoperative complications. Two patients returned to the operating room: one for endoscopic release of an inadvertently-sutured nasogastric tube during creation of the duodeno-ileal anastomosis and another patient for a port-site infection. Minor postoperative complications included carpal tunnel syndrome exacerbation (n = 1), which did not require surgical intervention. The median length of stay was 3.0 days (range 2-13). Two patients were readmitted within 30 day due to fluid retention and incarcerated umbilical hernia. The percentages of excess body weight loss (EBWL) at 1, 3, 6, 9, 12, and 18 months were 18.9, 36.4, 54.5, 67.4, 73.9, and 82.42 %, respectively. No mortality occurred in this study. Robotically assisted laparoscopic technique for BPD/DS is a feasible, safe, and effective alternative for weight loss surgery with excellent outcomes. PMID- 27000923 TI - Comparison of anesthetic management and outcomes of robot-assisted versus open radical cystectomy. AB - Robot-assisted cystectomy surgery may be advantageous for patients. The purpose of this study was to compare anesthetic management and outcomes in patients undergoing robot-assisted versus open radical cystectomy. In a retrospective review of 256 cystectomy procedures, procedure duration, blood loss, respiratory parameters, recovery room opiate consumption, pain scores and antiemetic use in the recovery room, and hospital length of stay were compared. After exclusions, 96 robot-assisted and 102 open procedures were analyzed. Anesthesia and surgery duration were significantly longer in the robot-assisted group, while the length of hospital stay was significantly shorter in the robot-assisted group: 7.1 +/- 5.8 versus 9.8 +/- 5.03 days, p = 0.0005. Estimated blood loss was 601.8 +/- 491.4 ml in the open group versus 257.7 +/- 164.3 ml in the robot-assisted group, p < 0.0001. Recovery room opiate consumption was significantly less in the robot assisted group: 9.5 +/- 8.9 versus 12.6 +/- 9.9 mg (morphine equivalents), p = 0.02. The highest recorded respiratory rate was significantly higher in the robot assisted group, as was the highest recorded peak airway pressure. Among patients with arterial blood gas data, the highest arterial partial pressure of CO2 was significantly greater in the robot-assisted group than in the open surgery group: 42.6 +/- 5.6 versus 37.4 +/- 4.8 mmHg CO2, p = 0.0001. Surgeons and anesthesia providers can expect robot-assisted radical cystectomy surgery to last longer than traditional open surgery, but to be associated with less pain and blood loss. Positioning and abdominal insufflation for robot-assisted surgery may contribute to ventilation challenges. PMID- 27000924 TI - Forward kinematic analysis of in-vivo robot for stomach biopsy. AB - The introduction of robotic medical assistance in biopsy and stomach cavity exploration is one of the most important milestones in the field of medical science. The research is still in its infancy and many issues like limitations in dexterity, control, and abdominal cavity vision are the main concerns of many researchers around the globe. This paper presents the design aspects and the kinematic analysis of a 4 degrees of freedom (DOF) hyper-redundant in-vivo robot for stomach biopsy. The proposed robot will be inserted through the tool channel of a conventional 4-DOF endoscope and this will increase the dexterity and ease in reaching the furthest parts of the stomach beyond the duodenum. Unlike the traditional biopsy tool, the present design will enhance dexterity due to its 4 DOF in addition to the endoscope's DOF. The endoscope will be positioned at the entrance to the stomach in the esophagus and the robot will move to the desired position inside the stomach for biopsy and exploration. The current robot is wire actuated and possesses better maneuverability. The forward kinematic analysis of the proposed robot is presented in this paper. PMID- 27000925 TI - Impact of trainee involvement with robotic-assisted radical prostatectomy. AB - Robotic-assisted surgery has been rapidly adopted within urology practice. As a result, academic centers are challenged with the burden of how to effectively train residents and fellows to perform robotic-assisted surgery without compromising outcomes. We evaluated the perioperative outcomes of trainee involvement with robotic-assisted radical prostatectomy (RARP) within our healthcare organization. We retrospectively reviewed RARP cases performed at our institution between September 2008 and December 2010 using a single da Vinci robotic platform. Trainees consisted of urology residents and fellows who operated with staff surgeons on select operating days, whereas two staff surgeon teams performed RARP on alternate days. We compared clinicopathologic variables including operating time, estimated blood loss, surgical margin rates, and complication rates between the trainee and staff-only surgeon groups. Overall, 1,019 RARP surgeries were performed within the study period and trainees participated in 162 cases (16 %). Clinical characteristics were similar between men undergoing surgery with a trainee and those without. Positive surgical margin rates were lower for patients with pT2 disease for cases with trainee involvement (11 vs. 19 %, p = 0.02), although overall margin rates and margin rates for patients with pT3 disease were similar between the groups (p = 0.34). Surgical cases involving trainees were longer (241 vs. 200 min, p < 0.001) and resulted in higher estimated blood loss (190 vs. 120 mL, p < 0.001) than the two staff surgeon cases. However, transfusion rates as well as intraoperative and postoperative complication rates did not differ significantly between groups. In conclusion, surgical margin rates were lower in teaching cases for patients with pT2 disease. Importantly, trainee involvement in RARP is safe, with similar perioperative outcomes to staff-only surgical cases. This information may be useful for training and surgical planning. PMID- 27000926 TI - An analysis of the impact of previous laparoscopic hysterectomy experience on the learning curve for robotic hysterectomy. AB - To analyze and compare the safety and perioperative outcomes of newly trained robotic surgeons with previous laparoscopic hysterectomy experience (TLH Exp) and those without previous laparoscopic hysterectomy experience (Non-TLH Exp). The purpose is to determine the effect of previous advanced laparoscopic skills on the performance in robotic assisted laparoscopic surgery. We will also compare the perioperative outcomes between the total laparoscopic hysterectomies (TLH), and robotic assisted laparoscopic hysterectomies (RALH) of a single experienced (TLH Exp) robotic surgeon. The purpose is to determine benefits and/or risks, if any, of one approach over the other in the hands of an experienced laparoscopic surgeon. Prospective data were collected on the first consecutive series of RALH performed by (TLH Exp) and (Non-TLH Exp) surgeons, with perioperative outcomes and morbidity being evaluated. In addition, retrsopective data were collected on a consecutive series of patients in a TLH group and compared with the outcomes in the robotic group for benign hysterectomies by the same surgeon. The parameters that were analyzed for associations with these two groups were estimated blood loss (EBL), Hb drop, length of hospital stay (LOS), procedure time, pain medication use, and complications. The (TLH Exp) group had 64 patients, and the (Non-TLH Exp) group had 72 patients. When comparing patients in the (TLH Exp) group with patients in (Non-TLH Exp) group, the mean age was 44 and 45 (P = 0.8), mean BMI was 27.7 and 29.5 kg/m(2) (P = 0.2), mean procedure time was 121 and 174 min (P < 0.05), mean console time was 70 and 119 min (P < 0.05), mean EBL was 64 and 84 ml (P = 0.3), with a Hb drop 1.7 and 1.33 (P = 0.2), uterine weight was 192 and 205 gms (P = 0.7), and length of stay was 1.07 and 1.33 days (P = 0.2), respectively. The (TLH Exp) surgeons had a lower OR, procedure and console time, but a higher hemoglobin drop, with no difference in EBL. There were no operative deaths, or conversions in either group. Morbidity occurred in two patients (3 %) in each group, with no statistically significant difference between the groups. In the (TLH Exp) group it included a blood transfusion and a readmission for a postoperative ileus. In the (Non-TLH Exp), the complications included a blood transfusion and a return to the OR for a vaginal cuff dehiscence. When comparing a single (TLH Exp) surgeon's own TLH versus RALH, there were 64 RALH and 49 TLH cases. There was a statistically significant difference in the mean procedure time 121.1 versus 88.8 min (P < 0.05), mean Hb drop 1.7 versus 2.3 (P < 0.05), and mean EBL 64.2 versus 158 ml (P < 0.05), respectively. The RALH group had a longer procedure time, but lower Hb drop, and less estimated blood loss. There were no operative deaths, or conversions in either group. Morbidity occurred in 2 patients in the robotic group, and included one blood transfusion, and one postoperative ileus. There were no complications noted in the laparoscopic hysterectomy group. Previous advanced laparoscopic skills appear to only significantly impact the length of the procedure, but not other variables. Robotic surgery may level the playing field between the basic and advanced laparoscopic surgeon for robotic assisted laparoscopic hysterectomy. In comparing the outcomes of RALH versus TLH by a single surgeon, the robotic assistance appeared to lengthen the procedure time, but reduce the amount of blood loss. Robotic surgery may offer a benefit of reduced blood loss at the expense of longer operating time. Similar studies including different surgeons are needed to validate these points, and thereby determine the risk-benefit balance between the two approaches for benign simple hysterectomies. PMID- 27000927 TI - Robotic-assisted laparoscopic radical prostatectomy after aborted retropubic radical prostatectomy. AB - Robotic-assisted laparoscopic prostatectomy (RALP) has surged in popularity since US Food and Drug Administration approval in 2000. Advantages include improved visualization and increased instrument dexterity within the pelvis. Obesity and narrow pelves have been associated with increased difficulty during open retropubic radical prostatectomy (RRP), but the robotic platform theoretically allows one to perform a radical prostatectomy despite these challenges. We present an example of a RALP performed following an aborted RRP. A 49-year-old male with intermediate risk prostate cancer and body mass index of 38 kg/m(2) presented for RALP after RRP was aborted by an experienced open surgeon following incision of the endopelvic fascia due to poor visualization, a prominent pubic tubercle, and a narrow pelvis. The enhanced visualization and precision of the robotic platform allowed adequate exposure of the prostate and allowed us to proceed with an uncomplicated prostatectomy, which was not possible to perform easily via an open approach. The bladder was densely adherent to the pubis and the anterior prostatic contour and apex were difficult to develop due to a dense fibrotic reaction from the previous endopelvic fascia incision. However, we were able to successfully complete RALP with subtle technical modifications. Estimated blood loss was 160 mL and operating time was 145 min. The patient's pathology was significant for a positive peri-prostatic lymph node and he has been referred to radiation oncology for adjuvant radiotherapy and androgen deprivation therapy. At 3 months follow-up he had a prostate-specific antigen level of 0.06 ng/mL, partial erections, and mild urinary incontinence requiring one pad per day. Superior intracorporeal laparoscopic visualization and improved instrument dexterity afforded by the robotic surgical platform may make RALP the preferred approach in obese men or men with difficult pelvic anatomy who are deemed poor RRP candidates. PMID- 27000928 TI - A comparison of surgeon's postural muscle activity during robotic-assisted and laparoscopic rectal surgery. AB - This study compared the muscular activity in the surgeon's neck and upper limbs during robotic-assisted laparoscopic (R-Lap) surgery and conventional laparoscopic (C-Lap) surgery. Two surgeons performed the same procedure of R-Lap and C-Lap low anterior resection, and real-time surface electromyography was recorded in bilateral cervical erector spinae, upper trapezius (UT) and anterior deltoid muscles for over 60 min in each procedure. In one surgeon, forearm muscle activities were also recorded during robotic surgery. Similar levels of cervical muscle activity were demonstrated in both types of surgery. One surgeon showed much higher activity in the left UT muscle during robotic surgery. In the second surgeon, C-Lap was associated with much higher levels of muscle activity in both UT muscles. This may be related to the bilateral abducted arm posture required in maneuvering the laparoscopic instruments. In the forearm region, the "ulnaris" muscles for wrist flexion and extension bilaterally showed high amplitudes during robotic-assisted surgery. Robotic-assisted surgery seemed to demand a higher level of muscle work in the forearm region while greater efforts of shoulder muscles were involved during laparoscopic surgery. There are also individual variations in postural habits and motor control that can affect the muscle activation patterns. This study demonstrated a method of objectively examining the surgeon's physical workload during real-time surgery in the operating theatre, and further research should explore the surgeon's workload in a larger group of surgeons performing different surgical procedures. PMID- 27000929 TI - Robotic-assisted simple prostatectomy with clamping of bilateral hypogastric arteries. AB - To present a case of laparoscopic robotic-assisted simple prostatectomy with temporary clamping of the bilateral hypogastric arteries. A 74-year-old patient with large prostatic adenoma (> 80 ml) underwent robotic-assisted laparoscopic transvesical adenoma enucleation according to Sotelo's technique. The hypogastric arteries were isolated just below the ureteral cross with the iliac vessels and bilaterally occluded for 12 minutes during enucleation of the adenoma. The patient's pain was mild after surgery and he required short-term analgesics and antibiotic prophylaxis. Blood loss was 80 ml. The transient occlusion of the internal iliac arteries is a proven maneuver to reduce bleeding during pelvic surgery. We propose the temporary clamping of the bilateral internal iliac arteries as a safe and rapid surgical maneuver to reduce the intraoperative risk of bleeding, especially when performing first procedures. PMID- 27000930 TI - A review of the effects of some endocrinological factors on respiratory mechanics. AB - CONTEXT: Endocrinological factors have been recently described to affect respiratory mechanics. OBJECTIVE: To review recent literature data, most of all obtained by the end-inflation occlusion method, describing the effects of molecules of endocrinological interest such as endothelin, erythropoietin and renin-angiotensin, on respiratory mechanics parameters. METHODS: The papers considered in this review were found by inserting in Pubmed/Medline the following indexing terms: hormones, endothelin, erythropoietin, angiotensin and respiratory mechanics. RESULTS: It was found that the above cited molecules, beside their well known physiological main effects, exhibit influences on respiratory mechanics, most of all on the airflow resistance, which was described to be increased by endothelin and angiotensin, and decreased by erythropoietin. CONCLUSIONS: A number of molecules of biological interest exhibit unexpected influences on respiratory mechanics. The clinical effects depend on the consequences of modified inspiratory pressure values the respiratory muscles have to perform for a given breathing pattern. PMID- 27000931 TI - My mum's decision changed my view of assisted dying. PMID- 27000932 TI - In vivo effects of curcumin on the paraoxonase, carbonic anhydrase, glucose-6 phosphate dehydrogenase and beta-glucosidase enzyme activities in dextran sulphate sodium-induced ulcerative colitis mice. AB - Increases in the risk of infections and malignancy due to immune suppressive therapies of inflammatory bowel diseases (IBDs) have led the researchers to focus on more nontoxic and acceptable natural products like curcumin. Here we investigate whether prophylactic and therapeutic application of the curcumin alters the enzyme activities of paraoxonase (PON), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and cytosolic beta-glucosidase in dextran sulphate sodium (DSS)-induced ulcerative colitis mice. Prophylactic application of curcumin resulted in higher MPO activity, less body weight loss and longer colon lengths compared to therapeutic group indicating preventive role of curcumin in IBDs. DSS-induced decrease in liver and serum PON activities were completely recovered by prophylactic administration of curcumin. DSS-induced reduction in liver cytosolic beta-glucosidase activity was not affected by curcumin neither in the prophylactic group nor in the therapeutic group. Erythrocyte CA activity was significantly increased in curcumin groups, however no remarkable change in G6PD activity was observed. PMID- 27000933 TI - Antiplatelet pyrazolopyridines derivatives: pharmacological, biochemical and toxicological characterization. AB - Platelet aggregation is one of the main events involved in vascular thrombus formation. Recently, N'-substituted-phenylmethylene-3-methyl-1,6-diphenyl-1H pyrazolo[3,4-b]pyridine-4-carbohydrazides were described as antiplatelet derivatives. In this work, we explore the properties of these antiplatelet agents through a series of pharmacological, biochemical and toxicological studies. The antiplatelet activity of each derivative was confirmed as 3a, 3b and 3 h significantly inhibited human platelet aggregation induced by arachidonic acid, with no detectable effect on clotting factors or healthy erythrocytes. Importantly, mice treated with derivative 3a showed a higher survival rate at an in vivo model of pulmonary thromboembolism with a lower bleeding risk in comparison to aspirin. The in silico studies pointed a series of structural parameters related to thromboxane synthase (TXS) inhibition by 3a, which was confirmed by tracking plasma levels of PGE2 and TXB2 through an in vitro enzyme immunoassay. Derivative 3a showed selective TXS inhibition allied with low bleeding risk and increased animal survival, revealing the derivative as a promising candidate for treatment of cardiovascular diseases. PMID- 27000934 TI - Margaret McCartney: Looking for dementia--in the name of "awareness". PMID- 27000935 TI - Corrigendum. PMID- 27000936 TI - Interleukin 33: an innate alarm for adaptive responses beyond Th2 immunity emerging roles in obesity, intestinal inflammation, and cancer. AB - Interleukin (IL)-33, a member of the IL-1 family, was originally described in 2005 as a potent initiator of type 2 immunity found during allergic inflammation and parasitic infections. IL-33 has been shown to play important and potent roles bridging innate and adaptive immunity in the regulation of tissue homeostasis, injury, and repair. Recent discoveries have extended the range of functions for IL-33 beyond type 2 conditions and its role as an alarmin at barrier sites, with emerging central roles for IL-33 in T-cell regulation, obesity, viral and tumor immunity. Here, we review the recent advances on how IL-33 activity is regulated, its immunomodulatory properties on innate and adaptive cells, and the newly discovered roles of IL-33 in obesity, intestinal inflammation, and tumorigenesis. PMID- 27000937 TI - Headline writers find sweet spot with sugar tax. PMID- 27000938 TI - Computed tomography scan does not correlate with patient experience of nasal obstruction. AB - OBJECTIVES/HYPOTHESIS: Third-party payors have begun to demand imaging studies to document septal deviation prior to authorizing septoplasties. This study aims to determine whether septal deviation findings on computed tomography (CT) correlate with symptoms of nasal obstruction as determined by the Nasal Obstruction Symptom Evaluation (NOSE) scale. STUDY DESIGN: Prospective and retrospective chart review. METHODS: Patients 18 years or older undergoing CT scans, which included the nasal septum, were asked to complete a NOSE scale survey and report the laterality of any possible obstruction. Coronal CT images of subjects were graded by two blinded otolaryngologists and two blinded neuroradiologists using a grading system devised by the authors. RESULTS: Seventy-three subjects met inclusion/exclusion criteria. Interobserver reliability about the degree of septal deviation on CT scans was moderately good to substantial (kappa values, 0.43 to 0.72). There was poor correlation between NOSE scores and degree of deviation on CT scans (Kendall's tau, 0.031 to 0.045; P values all >.05). There was poor concordance between the side of symptoms that patients reported and the side that observers thought was most deviated on CT. CONCLUSIONS: There is little correlation between septal deviation findings on CT scans and symptoms of nasal obstruction. The results do not support a role for CT scans as either a clinically meaningful or necessary test to investigate uncomplicated nasal obstruction. LEVEL OF EVIDENCE: 4. PMID- 27000939 TI - CymA and Exogenous Flavins Improve Extracellular Electron Transfer and Couple It to Cell Growth in Mtr-Expressing Escherichia coli. AB - Introducing extracellular electron transfer pathways into heterologous organisms offers the opportunity to explore fundamental biogeochemical processes and to biologically alter redox states of exogenous metals for various applications. While expression of the MtrCAB electron nanoconduit from Shewanella oneidensis MR 1 permits extracellular electron transfer in Escherichia coli, the low electron flux and absence of growth in these cells limits their practicality for such applications. Here we investigate how the rate of electron transfer to extracellular Fe(III) and cell survival in engineered E. coli are affected by mimicking different features of the S. oneidensis pathway: the number of electron nanoconduits, the link between the quinol pool and MtrA, and the presence of flavin-dependent electron transfer. While increasing the number of pathways does not significantly improve the extracellular electron transfer rate or cell survival, using the native inner membrane component, CymA, significantly improves the reduction rate of extracellular acceptors and increases cell viability. Strikingly, introducing both CymA and riboflavin to Mtr-expressing E. coli also allowed these cells to couple metal reduction to growth, which is the first time an increase in biomass of an engineered E. coli has been observed under Fe2O3 (s) reducing conditions. Overall, this work provides engineered E. coli strains for modulating extracellular metal reduction and elucidates critical factors for engineering extracellular electron transfer in heterologous organisms. PMID- 27000940 TI - Amygdala Hyperactivity in MAM Model of Schizophrenia is Normalized by Peripubertal Diazepam Administration. AB - In addition to prefrontal cortex (PFC) and hippocampus, amygdala may have a role in the pathophysiology of schizophrenia, given its pivotal role in emotion and extensive connectivity with the PFC and hippocampus. Moreover, abnormal activities of amygdala may be related to the anxiety observed in schizophrenia patients and at-risk adolescents. These at-risk subjects demonstrated heightened levels of anxiety, which are correlated with the onset of psychosis later in life. Similarly, rats that received methyl azoxymethanol acetate (MAM) gestationally exhibited higher levels of anxiety peripubertally. In the current study, the heightened anxiety was also observed in adult MAM animals, as well as higher firing rates of BLA neurons in both peripubertal and adult MAM rats. In addition, the power of BLA theta oscillations of adult MAM rats showed a larger increase in response to conditioned stimuli (CS). We showed previously that administration of the antianxiety drug diazepam during the peripubertal period prevents the hyperdopaminergic state in adult MAM rats. In this study, we found that peripubertal diazepam treatment reduced heightened anxiety, decreased BLA neuron firing rates and attenuated the CS-induced increase in BLA theta power in adult MAM rats, supporting a persistent normalization by this treatment. This study provides a link between BLA hyperactivity and anxiety in schizophrenia model rats and that circumvention of stress may prevent the emergence of pathology in the adult. PMID- 27000941 TI - SIRT3 Deficiency Induces Endothelial Insulin Resistance and Blunts Endothelial Dependent Vasorelaxation in Mice and Human with Obesity. AB - Recent evidence implicates the critical role of Sirtuin 3 (SIRT3) in the development of many metabolic diseases, but the contribution of SIRT3 to vascular homeostasis remains largely unknown. The aim of this study was to investigate the role of SIRT3 in endothelial insulin resistance and vascular dysfunction in obesity. We found an impaired insulin-induced mesenteric vasorelaxation and concomitant reduced vascular SIRT3 expression in morbid obese human subjects compared with the non-obese subjects. Downregulation of SIRT3 in cultured human endothelial cells increased mitochondrial reactive oxygen species (mtROS) and impaired insulin signaling as evidenced by decreased phosphorylation of Akt and endothelial nitric oxide synthase and subsequent reduced nitric oxide (NO) release. In addition, obese mice induced by 24-week high-fat diet (HFD) displayed an impaired endothelium-dependent vasorelaxation to both insulin and acetylcholine, which was further exacerbated by the gene deletion of Sirt3. Scavenging of mtROS not only restored insulin-stimulated NO production in SIRT3 knockdown cells, but also improved insulin-induced vasorelaxation in SIRT3 knockout mice fed with HFD. Taken together, our findings suggest that SIRT3 positively regulates endothelial insulin sensitivity and show that SIRT3 deficiency and resultant increased mtROS contribute to vascular dysfunction in obesity. PMID- 27000942 TI - Larval growth rate is associated with the composition of the gut microbiota in the Glanville fritillary butterfly. AB - The rapidly increasing body of literature on commensal microbiota has revealed a large phylotypic and functional diversity of microbes associated with vertebrates and invertebrates. In insects, the gut microbiota plays a role in digestion and metabolism of the host as well as protects the host against pathogens. In the study reported here, we sampled gut microbiota of the larvae of the Glanville fritillary butterfly (Melitaea cinxia). The larvae were collected from the field or reared in the laboratory. This butterfly has two host plant species, Plantago lanceolata and Veronica spicata, and the host plant species is known from previous studies to influence larval growth rate. However, our results demonstrate that about 50 % of the variation in larval growth rate can be attributed to the effect of the gut microbial composition plus the joint effect of microbiota and the host plant species, while host plant species alone makes no significant contribution. Our results support previous studies showing that diet influences the gut microbiota but, more unexpectedly, that the composition of the gut microbiota significantly influences larval growth rate. We suggest that host plant effects on larval growth and development observed in many previous studies may be mediated via the gut microbiota. While we measured the growth rate only in laboratory-reared larvae, the similarity of the gut microbial composition between samples from field-collected and laboratory-reared larvae suggests that the results can be generalized to natural conditions. PMID- 27000943 TI - Understanding a migratory species in a changing world: climatic effects and demographic declines in the western monarch revealed by four decades of intensive monitoring. AB - Migratory animals pose unique challenges for conservation biologists, and we have much to learn about how migratory species respond to drivers of global change. Research has cast doubt on the stability of the eastern monarch butterfly (Danaus plexippus) population in North America, but the western monarchs have not been as intensively examined. Using a Bayesian hierarchical model, sightings of western monarchs over approximately 40 years were investigated using summer flight records from ten sites along an elevational transect in Northern California. Multiple weather variables were examined, including local and regional temperature and precipitation. Population trends from the ten focal sites and a subset of western overwintering sites were compared to summer and overwintering data from the eastern migration. Records showed western overwintering grounds and western breeding grounds had negative trends over time, with declines concentrated early in the breeding season, which were potentially more severe than in the eastern population. Temporal variation in the western monarch also appears to be largely independent of (uncorrelated with) the dynamics in the east. For our focal sites, warmer temperatures had positive effects during winter and spring, and precipitation had a positive effect during spring. These climatic associations add to our understanding of biotic-abiotic interactions in a migratory butterfly, but shifting climatic conditions do not explain the overall, long-term, negative population trajectory observed in our data. PMID- 27000944 TI - Irresistible ants: exposure to novel toxic prey increases consumption over multiple temporal scales. AB - As species become increasingly exposed to novel challenges, it is critical to understand how evolutionary (i.e., generational) and plastic (i.e., within lifetime) responses work together to determine a species' fate or predict its distribution. The introduction of non-native species imposes novel pressures on the native species that they encounter. Understanding how native species exposed to toxic or distasteful invaders change their feeding behavior can provide insight into their ability to cope with these novel threats as well as broader questions about the evolution of this behavior. We demonstrated that native eastern fence lizards do not avoid consuming invasive fire ants following repeated exposure to this toxic prey. Rather fence lizards increased their consumption of these ants following exposure on three different temporal scales. Lizards ate more fire ants when they were exposed to this toxic prey over successive days. Lizards consumed more fire ants if they had been exposed to fire ants as juveniles 6 months earlier. Finally, lizards from populations exposed to fire ants over multiple generations consumed more fire ants than those from fire ant-free areas. These results suggest that the potentially lethal consumption of fire ants may carry benefits resulting in selection for this behavior, and learning that persists long after initial exposure. Future research on the response of native predators to venomous prey over multiple temporal scales will be valuable in determining the long-term effects of invasion by these novel threats. PMID- 27000945 TI - Male preference for female pubic hair: an evolutionary view. AB - SUMMARY: The ectoparasite avoidance hypothesis proposes that human hairlessness was favoured by sexual selection, because hairless individuals suffered from lower parasite loads. Females have seemingly less hairy bodies than men suggesting that the selection toward hairlessness is more intense in females than in males. This study examined male preference for hairy and shaved female genitalia. Pubic hair, although still functional in terms of dissipation of phermononal secretions, was perceived by heterosexual males recruited in the university (age range: 19-38 years, N = 96) as much less attractive as shaved female genitalia. Males who were more disgust sensitive and those who were sexually unrestricted showed a stronger preference for shaved genitalia than others. Self-reported frequency of pornography consumption was associated, contrary to expectations, with a stronger preference for hairy genitalia which suggests that this may be a result of negative frequency dependent selection. Older males also preferred hairy genitalia more than younger males. Overall, these results suggest that a preference for shaved genitalia may be explained by the superficial resemblance of pubic hair with chest hair, which is less developed as in our evolutionary past, perhaps due to the benefits associated with ectoparasite avoidance. PMID- 27000946 TI - Therapeutic efficacy of natural dipeptide carnosine against human cervical carcinoma cells. AB - Natural substances have been attracted several researchers in the recent years, because of its potential antioxidant, anti-inflammatory and anti-cancer properties. We have investigated the effect of carnosine on cell viability, apoptosis, DNA damage, reactive oxygen species (ROS) and caspase 3 enzyme expression in human cervical carcinoma and Madin-Darby Kidney Cells (MDCK) cells. Carnosine inhibited cancer cell growth up to 23%. ROS level was increased up to 30 and 31% in MDCK and HeLa cells respectively. Tunnel assay showed 42 and 14% of positive apoptotic cells in cancer and normal cells respectively. The alteration in mitochondrial and nuclear morphology was determined. The extended lace-like network of normal mitochondria found in control cells. Carnosine treatment significantly altered the mitochondrial morphology of normal cervical carcinoma cell. Mitochondria were condensed clump structures in carnosine treated cancer cells. Carnosine reduced the number of colonies of cervical carcinoma cells. Caspase 3 expression was corresponded to the appearance of immunofluorescence in the cytoplasm. Caspase 3 expression was gradually increased in cervical carcinoma cells. In Silico, docking study was performed to recognize the binding activity of carnosine against a subunit of the caspase 3, and carnosine was able to bind to the drug binding pocket of caspase 3. The glide energy is -5.2 kcal/mol, suggesting the high binding affinity of carnosine to caspase 3. Taking all these data together, the natural dipeptide L-carnosine could be a suitable antiproliferative agent in cervical carcinoma cells. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27000947 TI - AhR modulates the IL-22-producing cell proliferation/recruitment in imiquimod induced psoriasis mouse model. AB - IL-22 has a detrimental role in skin inflammatory processes, for example in psoriasis. As transcription factor, AhR controls the IL-22 production by several cell types (i.e. Th17 cells). Here, we analyzed the role of Ahr in IL-22 production by immune cells in the inflamed skin, using an imiquimod-induced psoriasis mouse model. Our results indicate that IL-22 is expressed in the ear of imiquimod-treated Ahr(-/-) mice but less than in wild-type mice. We then studied the role of AhR on three cell populations known to produce IL-22 in the skin: gammadelta T cells, Th17 cells, and ILC3, and a novel IL-22-producing cell type identified in this setting: CD4(-) CD8(-) TCRbeta(+) T cells. We showed that AhR is required for IL-22 production by Th17, but not by the three other cell types, in the imiquimod-treated ears. Moreover, AhR has a role in the recruitment of gammadelta T cells, ILC3, and CD4(-) CD8(-) TCRbeta(+) T cells into the inflamed skin or in their local proliferation. Taken together, AhR has a direct role in IL 22 production by Th17 cells in the mouse ear skin, but not by gammadelta T cells, CD4(-) CD8(-) TCRbeta(+) T cells and ILCs. PMID- 27000948 TI - Integration of Metabolic Modeling with Gene Co-expression Reveals Transcriptionally Programmed Reactions Explaining Robustness in Mycobacterium tuberculosis. AB - Robustness of metabolic networks is accomplished by gene regulation, modularity, re-routing of metabolites and plasticity. Here, we probed robustness against perturbations of biochemical reactions of M. tuberculosis in the form of predicting compensatory trends. In order to investigate the transcriptional programming of genes associated with correlated fluxes, we integrated with gene co-expression network. Knock down of the reactions NADH2r and ATPS responsible for producing the hub metabolites, and Central carbon metabolism had the highest proportion of their associated genes under transcriptional co-expression with genes of their flux correlated reactions. Reciprocal gene expression correlations were observed among compensatory routes, fresh activation of alternative routes and in the multi-copy genes of Cysteine synthase and of Phosphate transporter. Knock down of 46 reactions caused the activation of Isocitrate lyase or Malate synthase or both reactions, which are central to the persistent state of M. tuberculosis. A total of 30 new freshly activated routes including Cytochrome c oxidase, Lactate dehydrogenase, and Glycine cleavage system were predicted, which could be responsible for switching into dormant or persistent state. Thus, our integrated approach of exploring transcriptional programming of flux correlated reactions has the potential to unravel features of system architecture conferring robustness. PMID- 27000949 TI - Dietary intake of heat-killed Lactococcus lactis H61 delays age-related hearing loss in C57BL/6J mice. AB - Age-related hearing loss (AHL) is a common disorder associated with aging. In this study, we investigated the effect of the intake of heat-killed Lactococcus lactis subsp. cremoris H61 (strain H61) on AHL in C57BL/6J mice. Measurement of the auditory brainstem response (ABR) demonstrated that female mice at 9 months of age fed a diet containing 0.05% strain H61 for 6 months maintained a significantly lower ABR threshold than control mice. The age-related loss of neurons and hair cells in the cochlea was suppressed by the intake of strain H61. Faecal analysis of bacterial flora revealed that the intake of strain H61 increased the prevalence of Lactobacillales, which is positively correlated with hearing ability in mice. Furthermore, plasma fatty acid levels were negatively correlated with hearing ability. Overall, the results supported that the intake of heat-killed strain H61 for 6 months altered the intestinal flora, affected plasma metabolite levels, including fatty acid levels, and retarded AHL in mice. PMID- 27000950 TI - High-Sensitivity Cardiac Troponin Levels in Supraventricular Tachyarrhythmias. AB - BACKGROUND: High-sensitivity cardiac troponin assays have provided a significant contribution for the early diagnosis of cardiovascular events. However, elevated cardiac troponin levels may occur in other clinical situations as supraventricular tachyarrhythmias with concerns about the mechanism of this elevation. OBJECTIVES AND METHODS: The goal of this study was to describe the performance of high-sensitivity cardiac troponin T (hs-cTnT) assay in patients presenting to the emergency department with a primary diagnosis of supraventricular tachyarrhythmia and to evaluate its relation with cardiovascular events during follow-up. RESULTS: One hundred patients were included; mean age was 64 +/- 12 years and 59.8% were men. The most common arrhythmia at admission was atrial fibrillation (68%), followed by atrial flutter (16%) and reentrant tachycardia (16%). The results of the first determination of hs-cTnT were positive (>14 ng/L) in 44.2% of the patients and the second determination was positive in 50.7% of the cases. The variation between the first and the second troponin levels was 1 (0-5) ng/L, and was >7 ng/L in 24.6% of the cases, with a clear trend toward higher troponin values in reentrant tachycardias. Four events were reported at 30 days; in all the cases the patients had presented atrial fibrillation and there were no significant differences in hs-cTnT values. CONCLUSIONS: There are a significant number of patients with supraventricular tachyarrhythmias who present elevated hs-cTnT levels. The association of this elevation with cardiovascular events seems to be very low. PMID- 27000951 TI - Prevalence and contamination levels of listeria monocytogenes in ready-to-eat foods in Tokyo, Japan. AB - We surveyed prevalence and contamination levels of Listeria monocytogenes in ready-to-eat foods between 2000 and 2012 in Tokyo. L. monocytogenes was isolated from 52 (1.7%) out of 2,980 samples. Comparing the prevalence in the study period, 2.2% were positive in the former period (2000-2005) and 1.2% in the latter (2006-2012). Using the most probable number (MPN) technique, 32 samples were contaminated with fewer than 0.3 L. monocytogenes/g, 10 samples with 0.3 1.0/g and 4 samples with more than 1.0/g (the maximum was 2.3/g). The most common serovar was 1/2a, followed by 1/2b, 4b and 1/2c. We revealed that ready-to-eat foods in Tokyo were contaminated with L. monocytogenes, although the contamination levels were low. PMID- 27000953 TI - Inspirational decoys: a new hunt for effector targets. PMID- 27000952 TI - Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters. AB - Redox switches are important mediators in neoplastic, cardiovascular and neurological disorders. We recently identified spontaneous redox signals in neurons at the single mitochondrion level where transients of glutathione oxidation go along with shortening and re-elongation of the organelle. We now have developed advanced image and signal-processing methods to re-assess and extend previously obtained data. Here we analyze redox and pH signals of entire mitochondrial populations. In total, we quantified the effects of 628 redox and pH events in 1797 mitochondria from intercostal axons and neuromuscular synapses using optical sensors (mito-Grx1-roGFP2; mito-SypHer). We show that neuronal mitochondria can undergo multiple redox cycles exhibiting markedly different signal characteristics compared to single redox events. Redox and pH events occur more often in mitochondrial clusters (medium cluster size: 34.1 +/- 4.8 MUm(2)). Local clusters possess higher mitochondrial densities than the rest of the axon, suggesting morphological and functional inter-mitochondrial coupling. We find that cluster formation is redox sensitive and can be blocked by the antioxidant MitoQ. In a nerve crush paradigm, mitochondrial clusters form sequentially adjacent to the lesion site and oxidation spreads between mitochondria. Our methodology combines optical bioenergetics and advanced signal processing and allows quantitative assessment of entire mitochondrial populations. PMID- 27000954 TI - Old-growth temperate forests harbor hidden nitrogen-fixing bacteria. PMID- 27000955 TI - Resilience to seasonal heat wave episodes in a Mediterranean pine forest. AB - Short-term, intense heat waves (hamsins) are common in the eastern Mediterranean region and provide an opportunity to study the resilience of forests to such events that are predicted to increase in frequency and intensity. The response of a 50-yr-old Aleppo pine (Pinus halepensis) forest to hamsin events lasting 1-7 d was studied using 10 yr of eddy covariance and sap flow measurements. The highest frequency of heat waves was c. four per month, coinciding with the peak productivity period (March-April). During these events, net ecosystem carbon exchange (NEE) and canopy conductance (gc ) decreased by c. 60%, but evapotranspiration (ET) showed little change. Fast recovery was also observed with fluxes reaching pre-stress values within a day following the event. NEE and gc showed a strong response to vapor pressure deficit that weakened as soil moisture decreased, while sap flow was primarily responding to changes in soil moisture. On an annual scale, heat waves reduced NEE and gross primary productivity by c. 15% and 4%, respectively. Forest resilience to short-term extreme events such as heat waves is probably a key to its survival and must be accounted for to better predict the increasing impact on productivity and survival of such events in future climates. PMID- 27000956 TI - Evidence for foliar endophytic nitrogen fixation in a widely distributed subalpine conifer. AB - Coniferous forest nitrogen (N) budgets indicate unknown sources of N. A consistent association between limber pine (Pinus flexilis) and potential N2 fixing acetic acid bacteria (AAB) indicates that native foliar endophytes may supply subalpine forests with N. To assess whether the P. flexilis-AAB association is consistent across years, we re-sampled P. flexilis twigs at Niwot Ridge, CO and characterized needle endophyte communities via 16S rRNA Illumina sequencing. To investigate whether endophytes have access to foliar N2 , we incubated twigs with (13) N2 -enriched air and imaged radioisotope distribution in needles, the first experiment of its kind using (13) N. We used the acetylene reduction assay to test for nitrogenase activity within P. flexilis twigs four times from June to September. We found evidence for N2 fixation in P. flexilis foliage. N2 diffused readily into needles and nitrogenase activity was positive across sampling dates. We estimate that this association could provide 6.8-13.6 MUg N m(-2) d(-1) to P. flexilis stands. AAB dominated the P. flexilis needle endophyte community. We propose that foliar endophytes represent a low-cost, evolutionarily stable N2 -fixing strategy for long-lived conifers. This novel source of biological N2 fixation has fundamental implications for understanding forest N budgets. PMID- 27000957 TI - Corrigendum. PMID- 27000959 TI - Urological cancer: Atezolizumab effective against advanced disease. PMID- 27000958 TI - Driving CAR T-cells forward. AB - The engineered expression of chimeric antigen receptors (CARs) on the surface of T cells enables the redirection of T-cell specificity. Early clinical trials using CAR T cells for the treatment of patients with cancer showed modest results, but the impressive outcomes of several trials of CD19-targeted CAR T cells in the treatment of patients with B-cell malignancies have generated an increased enthusiasm for this approach. Important lessons have been derived from clinical trials of CD19-specific CAR T cells, and ongoing clinical trials are testing CAR designs directed at novel targets involved in haematological and solid malignancies. In this Review, we discuss these trials and present strategies that can increase the antitumour efficacy and safety of CAR T-cell therapy. Given the fast-moving nature of this field, we only discuss studies with direct translational application currently or soon-to-be tested in the clinical setting. PMID- 27000960 TI - Equal access to innovative therapies and precision cancer care. AB - Patients with cancers of differing histologies that express certain biomarkers are likely to benefit from treatment with targeted therapies. However, targets can be present in malignancies other than those indicated by a drug's label, and as a result, affected patients will have no access to those potentially useful drugs. To tackle this issue, the French National Cancer Institute developed the AcSe Programme in 2013. This programme is designed to make treatment decisions or recommendations on the basis of the presence of relevant biomarkers for malignancies with no targeted therapies available and also aims to improve safety, and evaluate the efficacy of targeted drugs used outside of their approved indications. Patients across France have access to molecular testing in 28 molecular genetics centres and to targeted therapies within phase II trials provided no other trials exist in which they could reasonably be included. Trials include patients below the age of 18 if safe dosing data are available. As of January 2016, 183 French clinical sites and over 7,000 patients are participating in AcSe led trials. Proof of concept is being demonstrated through trials designed to investigate the effectiveness of crizotinib and vemurafenib in a wide variety of cancers. PMID- 27000961 TI - Haematological cancer: PomCyDex - a lower-cost option in refractory myeloma? PMID- 27000964 TI - Doctors who take company cash are more likely to prescribe brand name drugs, analysis finds. PMID- 27000963 TI - Beta-tricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo. AB - The drawbacks of traditional bone-defect treatments have prompted the exploration of bone tissue engineering. This study aimed to explore suitable beta-tricalcium phosphate (beta-TCP) granules for bone regeneration and identify an efficient method to establish beta-TCP-based osteo-regenerators. beta-TCP granules with diameters of 1 mm and 1-2.5 mm were evaluated in vitro. The beta-TCP granules with superior osteogenic properties were used to establish in vivo bioreactors, referred to as osteo-regenerators, which were fabricated using two different methods. Improved proliferation of bone mesenchymal stem cells (BMSCs), glucose consumption and ALP activity were observed for 1-2.5 mm beta-TCP compared with 1 mm granules (P < 0.05). In addition, BMSCs incubated with 1-2.5 mm beta-TCP expressed significantly higher levels of the genes for runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 and the osteogenesis-related proteins alkaline phosphatase, collagen type-1 and runt related transcription factor-2 compared with BMSCs incubated with 1 mm beta-TCP (P < 0.05). Fluorochrome labelling, micro-computed tomography and histological staining analyses indicated that the osteo-regenerator with two holes perforating the femur promoted significantly greater bone regeneration compared with the osteo-regenerator with a periosteum incision (P < 0.05). This study provides an alternative to biofunctionalized bioreactors that exhibits improved osteogenesis. PMID- 27000962 TI - Translating neoadjuvant therapy into survival benefits: one size does not fit all. AB - Neoadjuvant therapy has been established as an effective therapeutic approach for patients with locally advanced breast cancer. Similar outcomes between neoadjuvant and adjuvant chemotherapy have been demonstrated in several trials. Nevertheless, neoadjuvant therapy has some advantages over adjuvant therapy, including tumour downstaging, in vivo assessment of therapeutic efficacy, reduced treatment durations, and the need to enrol fewer patients for clinical trials to reach their preplanned objectives. The number of neoadjuvant trials in patients with breast cancer has increased substantially in the past 5 years, particularly in the context of HER2-positive disease. Substantial improvements in the pathological complete response rate to anti-HER2 therapy, a proposed surrogate end point for long-term clinical benefit, have been observed with neoadjuvant dual-agent HER2 blockade. Thus, it was hypothesized that this approach would provide additional survival benefits over standard-of-care therapy with the anti HER2 antibody trastuzumab in the adjuvant setting. Emerging data, however, are calling this notion into question. We discuss potential reasons why results of neoadjuvant trials of targeted therapies have not been mirrored in the adjuvant setting, and other than inherent differences in clinical-trial designs and statistical power, we consider how the biology of the disease, patient characteristics, and drug administration and schedule might influence the results. PMID- 27000965 TI - Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats. AB - Research in the treatment of gastric ulcer has involved the investigation of new alternatives, such as anti-depressant drugs. The present study was designed to investigate the gastroprotective effects of fluoxetine against indomethacin and alcohol induced gastric ulcers in rats and the potential mechanisms of that effect. Fluoxetine (20 mg/kg) was administered IP for 14 days. For comparative purposes, other rats were treated with ranitidine (30 mg/kg). Thereafter, after 24 h of fasting, INDO (100 mg/kg) or absolute alcohol (5 ml/kg) was administered to all rats (saline was administered to naive controls) and rats in each group were sacrificed 5 h (for INDO rats) or 1 h (for alcohol rats) later. Macroscopic examination revealed that both fluoxetine and ranitidine decreased ulcer scores in variable ratios, which was supported by microscopic histopathological examination. Biochemical analysis of fluoxetine- or ranitidine-pre-treated host tissues demonstrated reductions in tumor necrosis factor (TNF)-alpha and myeloperoxidase (MPO) levels and concomitant increases in gastric pH, nitric oxide (NO) and reduced glutathione (GSH) contents. Fluoxetine, more than ranitidine, also resulted in serotonin and histamine levels nearest to control values. Moreover, immuno-histochemical analysis showed that fluoxetine markedly enhanced expression of cyclo-oxygenases COX-1 and COX-2 in both models; in comparison, ranitidine did not affect COX-1 expression in either ulcer model but caused moderate increases in COX-2 expression in INDO-induced hosts and high expression in alcohol-induced hosts. The results here indicated fluoxetine exhibited better gastroprotective effects than ranitidine and this could be due to anti-secretory, anti-oxidant, anti-inflammatory and anti-histaminic effects of the drug, as well as a stabilization of gastric serotonin levels. PMID- 27000966 TI - Selection of urinary sediment miRNAs as specific biomarkers of IgA nephropathy. AB - The miRNAs in urinary sediment are easy to obtain, which provides a new approach to searching for non-invasive biomarkers of IgA nephropathy (IgAN). Compared with normal controls (n = 3), 214 different miRNAs in the urinary sediment of IgAN (n = 9) were found by miRNA chip assay. By quantitative PCR analysis, miR-25-3p, miR 144-3p and miR-486-5p were confirmed to be significantly higher in IgAN (n = 93) than in the normal group (n = 82) or disease control (n = 40). These three miRNAs had good specificity and sensitivity for the diagnosis of IgAN by receiver operating characteristic curve analysis, in which the AUC value of miR-486-5p was the largest at 0.935. Urinary sediment miR-25-3p, miR-144-3p and miR-486-5p were demonstrated to be mainly derived from urinary erythrocytes, which were separated by CD235a magnetic beads. The increased expression of urinary erythrocyte miRNAs in IgAN patients was not associated with those in the blood erythrocytes. In addition, urinary supernatant microvesicles of miR-144-3p and miR-486-5p in the IgAN group were also significantly increased. This study showed that the miR-25 3p, miR-144-3p and miR-486-5p in urinary sediment were mainly derived from urinary erythrocytes, which could be non-invasive candidate biomarkers for IgA nephropathy. PMID- 27000967 TI - Overweight and obesity in children and adolescents from Serbia in the period 2001 2004 and 2011-2014. AB - SUMMARY: OBJECTIVE: In recent years an increasing prevalence in overweight and obesity of children and adolescents has been recorded worldwide. Childhood obesity is a risk factor for adulthood obesity. The aim of the study is to examine the prevalence of overweight and obesity in children and adolescents aged 7-19 in a 10-year long period in Serbia. SUBJECTS AND METHODS: Cross sectional investigation was conducted in the periods 2001-2004 and 2011-2014. The first investigation included 8965 individuals, 4344 schoolboys and 4621 schoolgirls aged 7-19, while the second investigation included 2507 schoolboys and 3083 schoolgirls. The body mass index (BMI kg m(-2)) was obtained from the recorded height and weight and the assessment of overweight and obesity was based on IOTF reference values. RESULTS: In the first period investigation overweight prevalence was detected in 18% of subjects (21.1% in boys and 15.1% in girls) and obesity prevalence in 5.5% of subjects (6.7% in boys and 4.4% in girls). In the second investigation the overweight and obesity prevalence was observed in 17.4% and 4.5% of subjects, respectively (20.6% in boys and 14.8% in girls; 5.3% in boys and 3.9% in girls). CONCLUSION: The results indicate that in the ten-year period there has been no increase in the number of overweight and obese children and adolescents in Serbia. PMID- 27000968 TI - Optimization of staged bioleaching of low-grade chalcopyrite ore in the presence and absence of chloride in the irrigating lixiviant: ANFIS simulation. AB - In this investigation, copper was bioleached from a low-grade chalcopyrite ore using a chloride-containing lixiviant. In this regard, firstly, the composition of the bacterial culture media was designed to control the cost in commercial application. The bacterial culture used in this process was acclimated to the presence of chloride in the lixiviant. Practically speaking, the modified culture helped the bio-heap-leaching system operate in the chloridic media. Compared to the copper recovery from the low-grade chalcopyrite by bioleaching in the absence of chloride, bioleaching in the presence of chloride resulted in improved copper recovery. The composition of the lixiviant used in this study was a modification with respect to the basal salts in 9 K medium to optimize the leaching process. When leaching the ore in columns, 76.81 % Cu (based on solid residues of bioleaching operation) was recovered by staged leaching with lixiviant containing 34.22 mM NaCl. The quantitative findings were supported by SEM/EDS observations, X-ray elemental mapping, and mineralogical analysis of the ore before and after leaching. Finally, Adaptive neuro-fuzzy inference system (ANFIS) was used to simulate the operational parameters affecting the bioleaching operation in chloride-sulfate system. PMID- 27000969 TI - Pitfall in first-trimester diagnosis of chorionicity in twin pregnancy. PMID- 27000971 TI - Electrochemical fecal pellet sensor for simultaneous real-time ex vivo detection of colonic serotonin signalling and motility. AB - Various investigations have focused on understanding the relationship between mucosal serotonin (5-HT) and colonic motility, however contradictory studies have questioned the importance of this intestinal transmitter. Here we described the fabrication and use of a fecal pellet electrochemical sensor that can be used to simultaneously detect the release of luminal 5-HT and colonic motility. Fecal pellet sensor devices were fabricated using carbon nanotube composite electrodes that were housed in 3D printed components in order to generate a device that had shape and size that mimicked a natural fecal pellet. Devices were fabricated where varying regions of the pellet contained the electrode. Devices showed that they were stable and sensitive for ex vivo detection of 5-HT, and no differences in the fecal pellet velocity was observed when compared to natural fecal pellets. The onset of mucosal 5-HT was observed prior to the movement of the fecal pellet. The release of mucosal 5-HT occurred oral to the fecal pellet and was linked to the contraction of the bowel wall that drove pellet propulsion. Taken, together these findings provide new insights into the role of mucosal 5-HT and suggest that the transmitter acts as a key initiator of fecal pellet propulsion. PMID- 27000970 TI - Glucosyl epi-cyclophellitol allows mechanism-based inactivation and structural analysis of human pancreatic alpha-amylase. AB - As part of a search for selective, mechanism-based covalent inhibitors of human pancreatic alpha-amylase we describe the chemoenzymatic synthesis of the disaccharide analog alpha-glucosyl epi-cyclophellitol, demonstrate its stoichiometric reaction with human pancreatic alpha-amylase and evaluate the time dependence of its inhibition. X-ray crystallographic analysis of the covalent derivative so formed confirms its reaction at the active site with formation of a covalent bond to the catalytic nucleophile D197. The structure illuminates the interactions with the active site and confirms OH4' on the nonreducing end sugar as a good site for attachment of fluorescent tags in generating probes for localization and quantitation of amylase in vivo. PMID- 27000972 TI - Highly selective fluorescent chemosensor for detection of Fe(3+) based on Fe3O4@ZnO. AB - The combination of fluorescent nanoparticles and specific molecular probes appears to be a promising strategy for developing fluorescent nanoprobes. In this work, L-cysteine (L-Cys) capped Fe3O4@ZnO core-shell nanoparticles were synthesized for the highly selective detection of Fe(3+). The proposed nanoprobe shows excellent fluorescent property and high selectivity for Fe(3+) due to the binding affinity of L-Cys with Fe(3+). The binding of Fe(3+) to the nanoprobe induces an apparent decrease of the fluorescence. Thus a highly selective fluorescent chemosensor for Fe(3+) was proposed based on Fe3O4@ZnO nanoprobe. The magnetism of the nanoprobe enables the facile separation of bound Fe(3+) from the sample solution with an external magnetic field, which effectively reduces the interference of matrix. The detection limit was 3 nmol L(-1) with a rapid response time of less than 1 min. The proposed method was applied to detect Fe(3+) in both serum and wastewater samples with acceptable performance. All above features indicated that the proposed fluorescent probe as sensing platform held great potential in applications of biological and analytical field. PMID- 27000973 TI - Serum Prolidase Activity as a Biomarker for Choroid Plexus Calcification. AB - The choroid plexus (CP) performs multiple functions such as secretion and reabsorption. CP also acts as the blood-cerebrospinal fluid barrier. Prolidase plays an important role in collagen metabolism by degrading imidodipeptides, in which proline or hydroxyproline residue is located at the C-terminal end. Serum prolidase activity (SPA) may reflect the degree of fibrosis and inflammation. Choroid plexus calcification (CPC) is considered as the physiological calcification of the brain, and CPC is diagnosed by the presence of calcification in the anatomical region on computed tomography (CT). Here, CPC and non-calcified CP were defined by Hounsfield Units (HU) values of > 150 and < 50, respectively. We aimed to measure SPA in subjects with CPC and those with non-calcified CP. This study included 89 subjects who were admitted to the neurology clinic and underwent CT: 44 subjects with CPC and 45 subjects with non-calcified CP. The neurological examination of all subjects was normal; namely, the subjects with CPC were asymptomatic. The SPA level was significantly higher in the CPC group than that in the non-calcified CP group (p < 0.002), and there was a significant positive correlation between vitamin D and SPA levels in the CPC group. In contrast, the vitamin D and parathyroid hormone levels were higher in the CPC group, but the difference was not statically significant (p > 0.05). These findings indicate that SPA is a biomarker for CPC that may be predictive of future brain disease. PMID- 27000974 TI - Cardiac Resynchronization Therapy Online: What Patients Find when Searching the World Wide Web. AB - BACKGROUND: To objectively assess the quality of information available on the World Wide Web on cardiac resynchronization therapy (CRT). Patients frequently search the internet regarding their healthcare issues. It has been shown that patients seeking information can help or hinder their healthcare outcomes depending on the quality of information consulted. On the internet, this information can be produced and published by anyone, resulting in the risk of patients accessing inaccurate and misleading information. METHODS: The search term "Cardiac Resynchronisation Therapy" was entered into the three most popular search engines and the first 50 pages on each were pooled and analyzed, after excluding websites inappropriate for objective review. The "LIDA" instrument (a validated tool for assessing quality of healthcare information websites) was to generate scores on Accessibility, Reliability, and Usability. Readability was assessed using the Flesch Reading Ease Score (FRES). RESULTS: Of the 150 web links, 41 sites met the eligibility criteria. The sites were assessed using the LIDA instrument and the FRES. A mean total LIDA score for all the websites assessed was 123.5 of a possible 165 (74.8%). The average Accessibility of the sites assessed was 50.1 of 60 (84.3%), on Usability 41.4 of 54 (76.6%), on Reliability 31.5 of 51 (61.7%), and 41.8 on FRES. There was a significant variability among sites and interestingly, there was no correlation between the sites' search engine ranking and their scores. CONCLUSION: This study has illustrated the variable quality of online material on the topic of CRT. Furthermore, there was also no apparent correlation between highly ranked, popular websites and their quality. Healthcare professionals should be encouraged to guide their patients toward the online material that contains reliable information. PMID- 27000975 TI - HAV & HBV vaccination among travellers participating in the National Health and Wellness Survey in five European countries. AB - BACKGROUND: A main cause of hepatitis A and B infections in European countries is travel to endemic countries. Most research on hepatitis vaccination among travellers from Europe has been conducted in airports or travel clinics, samples which potentially overrepresented frequent travellers. METHODS: 2102 respondents across France, Germany, Italy, Spain, and UK completed an internet-based questionnaire. Vaccination status, travel to endemic countries, and other characteristics were compared across frequent, occasional, and non-travellers. Logistic regressions tested association between vaccination and travel adjusting for potential confounders. RESULTS: Most respondents were occasional travellers (61%) and 24% were frequent travellers. Frequent travellers had 2.3-2.4 times the odds of being vaccinated relative to non-travellers, and odds of vaccination were 2.5-3.1 times higher among travellers to endemic areas relative to others (all p < .05). Frequent travellers were more aware of their vaccination status (HAV: 80% vs. 72%; HBV: 82% vs. 74%), though many who were vaccinated could not identify the number of injections to complete the series (47% vs. 29%) (all p < .05). CONCLUSION: Travel frequency and destination endemicity are associated with increased hepatitis A and B vaccination. The number of unvaccinated travellers and the lack of recall for the dosing schedule suggest the need to improve travellers' awareness and adherence to recommendations. PMID- 27000977 TI - Medication withdrawal in relapsing-remitting multiple sclerosis: why not? PMID- 27000976 TI - An Integrated Genomic Strategy Delineates Candidate Mediator Genes Regulating Grain Size and Weight in Rice. AB - The present study deployed a Mediator (MED) genes-mediated integrated genomic strategy for understanding the complex genetic architecture of grain size/weight quantitative trait in rice. The targeted multiplex amplicon resequencing of 55 MED genes annotated from whole rice genome in 384 accessions discovered 3971 SNPs, which were structurally and functionally annotated in diverse coding and non-coding sequence-components of genes. Association analysis, using the genotyping information of 3971 SNPs in a structured population of 384 accessions (with 50-100 kb linkage disequilibrium decay), detected 10 MED gene-derived SNPs significantly associated (46% combined phenotypic variation explained) with grain length, width and weight in rice. Of these, one strong grain weight-associated non-synonymous SNP (G/A)-carrying OsMED4_2 gene was validated successfully in low and high-grain weight parental accessions and homozygous individuals of a rice mapping population. The seed-specific expression, including differential up/down regulation of three grain size/weight-associated MED genes (including OsMED4_2) in six low and high-grain weight rice accessions was evident. Altogether, combinatorial genomic approach involving haplotype-based association analysis delineated diverse functionally relevant natural SNP-allelic variants in 10 MED genes, including three potential novel SNP haplotypes in an OsMED4_2 gene governing grain size/weight differentiation in rice. These molecular tags have potential to accelerate genomics-assisted crop improvement in rice. PMID- 27000978 TI - Muscle imaging in inherited and acquired muscle diseases. AB - In this review we discuss the use of conventional (computed tomography, magnetic resonance imaging, ultrasound) and advanced muscle imaging modalities (diffusion tensor imaging, magnetic resonance spectroscopy) in hereditary and acquired myopathies. We summarize the data on specific patterns of muscle involvement in the major categories of muscle disease and provide recommendations on how to use muscle imaging in this field of neuromuscular disorders. PMID- 27000979 TI - Beyond spinal muscular atrophy with lower extremity dominance: cerebellar hypoplasia associated with a novel mutation in BICD2. PMID- 27000980 TI - Stiff leg syndrome after epidural anesthesia. PMID- 27000981 TI - Elevated aspartate aminotransferase and lactate dehydrogenase levels are a constant finding in PLA2G6-associated neurodegeneration. PMID- 27000982 TI - Response to the letter 'Type 2 diabetes and amyotrophic lateral sclerosis'. PMID- 27000983 TI - Low serum levels of vitamin D are associated with post-stroke depression. PMID- 27000985 TI - Long-term changes in body proportions since 1983 to 2010 in children and adolescents from Krakow (Poland). AB - SUMMARY: The aim of the study was to assess changes in body proportions and the rate of growth in boys and girls from the population of Krakow (Poland) in the years 1983-2010. The children and adolescents analyzed in this study were included in three cross-sectional surveys conducted in Krakow in 1983, 2000 and 2010. The sample sizes were the following: 3,214 boys and 3,250 girls in 1983, 2,381 boys and 2,096 girls in 2000, 1,889 boys and 1,989 girls in 2010. The comparison of selected features and indices were made: subischial leg length, biacromial width, biiliac width, reciprocal ponderal index, skelic index, pelvi acromial index, shoulder-height ratio, pelvis-height ratio. To analyze the rate of growth the modeling functions of Preece-Baines (PB1) were used. Over the analyzed period, the children and adolescents from Krakow showed a positive secular trend for all the analyzed traits, especially consistent in the width of the pelvis and shoulders. The acceleration of development was reflected in the earlier pubertal spurt in the studied lengths and widths. The changes in body proportions showed a tendency to more slender body proportions in children between 3 and 8 years of age in girls and after puberty, and the relative shortening of the lower limbs. In the group of boys, there was a distinct widening of hips and pelvis, more pronounced than in height. In girls, similar changes were noted only until the period of puberty, and throughout the entire duration of ontogeny for the shoulders-height ratio. PMID- 27000986 TI - Dermatology team. PMID- 27000987 TI - HESX1 mutations in patients with congenital hypopituitarism: variable phenotypes with the same genotype. AB - INTRODUCTION: Mutations in the transcription factor HESX1 can cause isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD) with or without septo-optic dysplasia (SOD). So far there is no clear genotype phenotype correlation. PATIENTS AND RESULTS: We report four different recessive loss-of-function mutations in three unrelated families with CPHD and no midline defects or SOD. A homozygous p.R160C mutation was found by Sanger sequencing in two siblings from a consanguineous family. These patients presented with ACTH, TSH and GH deficiencies, severe anterior pituitary hypoplasia (APH) or pituitary aplasia (PA) and normal posterior pituitary. The p.R160C mutation was previously reported in a case with SOD, CPHD and ectopic posterior pituitary (EPP). Using exome sequencing, a homozygous p.I26T mutation was found in a Brazilian patient born to consanguineous parents. This patient had evolving CPHD, normal ACTH, APH and normal posterior pituitary (NPP). A previously reported patient homozygous for p.I26T had evolving CPHD and EPP. Finally, we identified compound heterozygous mutations in HESX1, p.[R159W];[R160H], in a patient with PA and CPHD. We showed that both of these mutations abrogate the ability of HESX1 to repress PROP1-mediated transcriptional activation. A patient homozygous for p.R160H was previously reported in a patient with CPHD, EPP, APH. CONCLUSION: These three examples demonstrate that HESX1 mutations cause variable clinical features in patients, which suggests an influence of modifier genes or environmental factors on the phenotype. PMID- 27000988 TI - Generalization of multisensory perceptual learning. AB - Life in a multisensory world requires the rapid and accurate integration of stimuli across the different senses. In this process, the temporal relationship between stimuli is critical in determining which stimuli share a common origin. Numerous studies have described a multisensory temporal binding window-the time window within which audiovisual stimuli are likely to be perceptually bound. In addition to characterizing this window's size, recent work has shown it to be malleable, with the capacity for substantial narrowing following perceptual training. However, the generalization of these effects to other measures of perception is not known. This question was examined by characterizing the ability of training on a simultaneity judgment task to influence perception of the temporally-dependent sound-induced flash illusion (SIFI). Results do not demonstrate a change in performance on the SIFI itself following training. However, data do show an improved ability to discriminate rapidly-presented two flash control conditions following training. Effects were specific to training and scaled with the degree of temporal window narrowing exhibited. Results do not support generalization of multisensory perceptual learning to other multisensory tasks. However, results do show that training results in improvements in visual temporal acuity, suggesting a generalization effect of multisensory training on unisensory abilities. PMID- 27000989 TI - Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours. AB - Treatment of high-risk childhood neuroblastoma is a clinical challenge which has been hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing. PMID- 27000990 TI - Application of CRISPR-mediated genome engineering in cancer research. AB - Cancer is a multistep process that arises from a series of genetic and epigenetic events. With recent technological advances there has been a burst in genome sequencing and epigenetic studies revealing a plethora of alterations that may contribute to cancer. However, the great challenge for the cancer research community is the systematic functional characterization of these genetic and epigenetic events to assess their role in cancer initiation and progression. Recent advances in genome engineering using CRISPR/Cas9, an ancient bacterial immune-like system, have revolutionized cancer genetics. Here we highlight the breakthroughs in the effective use of these novel genome-editing techniques, and we discuss the challenges and potential applications of these tools for cancer biology. PMID- 27000991 TI - G protein-coupled receptors as promising cancer targets. AB - G protein-coupled receptors (GPCRs) regulate an array of fundamental biological processes, such as growth, metabolism and homeostasis. Specifically, GPCRs are involved in cancer initiation and progression. However, compared with the involvement of the epidermal growth factor receptor in cancer, that of GPCRs have been largely ignored. Recent findings have implicated many GPCRs in tumorigenesis, tumor progression, invasion and metastasis. Moreover, GPCRs contribute to the establishment and maintenance of a microenvironment which is permissive for tumor formation and growth, including effects upon surrounding blood vessels, signaling molecules and the extracellular matrix. Thus, GPCRs are considered to be among the most useful drug targets against many solid cancers. Development of selective ligands targeting GPCRs may provide novel and effective treatment strategies against cancer and some anticancer compounds are now in clinical trials. Here, we focus on tumor related GPCRs, such as G protein-coupled receptor 30, the lysophosphatidic acid receptor, angiotensin receptors 1 and 2, the sphingosine 1-phosphate receptors and gastrin releasing peptide receptor. We also summarize their tissue distributions, activation and roles in tumorigenesis and discuss the potential use of GPCR agonists and antagonists in cancer therapy. PMID- 27000992 TI - Combination with gamma-secretase inhibitor prolongs treatment efficacy of BRAF inhibitor in BRAF-mutated melanoma cells. AB - Oncogenic triggering of the MAPK pathway in melanocytes results in senescence, and senescence escape is considered as one critical step for melanocytic transformation. In melanoma, induction of a senescent-like state by BRAF inhibitors (BRAFi) in a fraction of treated cells - instead of killing - contributes to the repression of tumor growth, but may also provide a source for relapse. Here, we demonstrate that NOTCH activation in melanocytes is not only growth-promoting but it also protects these cells against oncogene-induced senescence. In turn, treatment of melanoma cells with an inhibitor of the NOTCH activating enzyme gamma-secretase led to induction of a senescent-like status in a fraction of the cells but overall achieved only a moderate inhibition of melanoma cell growth. However, combination of gamma-secretase inhibitor (GSI) with BRAFi markedly increased the treatment efficacy particularly in long-term culture. Moreover, even melanoma cells starting to regrow after continuous BRAFi treatment - the major problem of BRAFi therapy in patients - can still be affected by the combination treatment. Thus, combining GSI with BRAFi increases the therapeutic efficacy by, at least partially, prolonging the senescent-like state of treated cells. PMID- 27000993 TI - Non-CSCs nourish CSCs through interleukin-17E-mediated activation of NF-kappaB and JAK/STAT3 signaling in human hepatocellular carcinoma. AB - Within the cancer stem cell (CSC) niche, non-CSCs play an indispensable role in facilitating a microenvironment capable of maintaining CSC properties. Non-CSCs contribute to not only the structure and topology of the tumor microenvironment but also the maintenance of the dynamic state of CSCs. Interleukin-17E (IL-17E/IL 25) is important in allergic inflammation and protection against parasitic infection. Moreover, it has also been demonstrated that IL-17E takes part in different cancers recently. Here, for the first time we demonstrate that discrepant expression of IL-17E and the IL-17 receptor B (IL-17RB) exists in Nanog positive (Nanog(Pos)) CSCs and Nanog negative (Nanog(Neg)) non-CSCs in hepatocellular carcinoma (HCC). Moreover, we further demonstrate that IL-17E binding to IL-17RB activates NF-kappaB and JAK/Stat3 pathways to promote proliferation and sustain self-renewal of CSCs in HCC. Meanwhile, the beneficial effect of IL-17E on Nanog(Pos) CSCs could be blocked by specific inhibitors of JAK and NF-kappaB signaling. All the findings indicated that non-CSC-derived secreted IL-17E binds IL-17RB on CSCs to signal via JAK/Stat3 and NF-kappaB pathways to mediate crosstalk between CSCs and non-CSCs. Therefore, IL-17E/IL 17RB signaling represents a potential therapeutic target for treatment of HCC. PMID- 27000994 TI - The degradation potential of PET bottles in the marine environment: An ATR-FTIR based approach. AB - The dominance and persistence of plastic debris in the marine environment are well documented. No information exists in respect to their lifespan in the marine environment. Nevertheless, the degradation potential of plastic litter items remains a critical issue for marine litter research. In the present study, polyethylene terephthalate bottles (PETs) collected from the submarine environment were characterized using ATR-FTIR in respect to their degradation potential attributed to environmental conditions. A temporal indication was used as indicative to the years of presence of the PETs in the environment as debris. PETs seem to remain robust for approximately fifteen years. Afterwards, a significant decrease of the native functional groups was recorded; some even disappear; or new-not typical for PETs-are created. At a later stage, using the PET time series collected from the Saronikos Gulf (Aegean Sea-E. Mediterranean), it was possible to date bottles that were collected from the bottom of the Ionian Sea (W. Greece). It is the first time that such a study has been conducted with samples that were actually degraded in the marine environment. PMID- 27000995 TI - Management of enteroatmospheric fistula with negative pressure wound therapy in open abdomen treatment: a multicentre observational study. AB - The management of enteroatmospheric fistula (EAF) in open abdomen (OA) therapy is challenging and associated with a high mortality rate. The introduction of negative pressure wound therapy (NPWT) in open abdomen management significantly improved the healing process and increased spontaneous fistula closure. Retrospectively, we analysed 16 patients with a total of 31 enteroatmospheric fistulas in open abdomen management who were treated using NPWT in four referral centres between 2004 and 2014. EAFs were diagnosed based on clinical examination and confirmed with imaging studies and classified into low (<200 ml/day), moderate (200-500 ml/day) and high (>500 ml/day) output fistulas. The study group consisted of five women and 11 men with the mean age of 52.6 years [standard deviation (SD) 11.9]. Since open abdomen management was implemented, the mean number of re-surgeries was 3.7 (SD 2.2). There were 24 EAFs located in the small bowel, while four were located in the colon. In three patients, EAF occurred at the anastomotic site. Thirteen fistulas were classified as low output (41.9%), two as moderate (6.5%) and 16 as high output fistulas (51.6%). The overall closure rate was 61.3%, with a mean time of 46.7 days (SD 43.4). In the remaining patients in whom fistula closure was not achieved (n = 12), a protruding mucosa was present. Analysing the cycle of negative pressure therapy, we surprisingly found that the spontaneous closure rate was 70% (7 of 10 EAFs) using intermittent setting of negative pressure, whereas in the group of patients treated with continuous pressure, 57% of EAFs closed spontaneously (12 of 21 EAFs). The mean number of NPWT dressing was 9 (SD 3.3; range 4-16). In two patients, we observed new fistulas that appeared during NPWT. Three patients died during therapy as a result of multi-organ failure. NPWT is a safe and efficient method characterised by a high spontaneous closure rate. However, in patients with mucosal protrusion of the EAFs, spontaneous closure appears to be impossible to achieve. PMID- 27000997 TI - The elusive minimum threshold concentration of levonorgestrel for contraceptive efficacy. PMID- 27000996 TI - Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: single and double dosing. AB - OBJECTIVE: To determine if differences exist in the pharmacokinetics (PK) of levonorgestrel-based emergency contraception (LNG-EC) in obese and normal body mass index (BMI) users and test whether doubling the dose of LNG-EC in obese women increases total and free (active) LNG serum concentrations. STUDY DESIGN: Healthy, reproductive-age women with obese and normal BMIs received 1.5mg LNG orally (ECx1) and then in a subsequent menstrual cycle, the obese group also received 3mg LNG (ECx2). Dosing occurred during the follicular phase. Total and free LNG PK parameters were obtained via serum samples through an indwelling catheter at 0, 0.5, 1, 1.5, 2, and 2.5h. The primary outcome was the difference in total and free LNG concentration maximum (Cmax) between ECx1 and ECx2 in the obese group. RESULTS: A total of 10 women enrolled and completed the study (normal BMI=5, median 22.8kg/m(2), range 20.8-23.7; obese BMI=5, 39.5kg/m(2), range 35.9-46.7). The total LNG Cmax for obese subjects following ECx1 (5.57+/ 2.48ng/mL) was significantly lower than the level observed in normal BMI women (10.30+/-2.47, p=.027). Notably, ECx2 increased the Cmax significantly (10.52+/ 2.76, p=.002); approximating the level in normal BMI subjects receiving ECx1. Free LNG Cmax followed a similar pattern. CONCLUSION: Obesity adversely impacts both the total and free Cmax levels of LNG EC and this likely explains its lack of efficacy in obese women. Doubling the dose appears to correct the obesity related PK changes but additional research is needed to determine if this also improves EC effectiveness in obese women. IMPLICATIONS: This study demonstrates that obesity interferes with the pharmacokinetics of LNG EC, and that doubling the dose may be an effective strategy to improve its efficacy in obese women. PMID- 27000998 TI - Pregnancy following hysteroscopic sterilization at an Urban Abortion Clinic- A case series: Are We looking in the wrong places? AB - OBJECTIVE: Hysteroscopic sterilization (HS) has become one of the most common permanent contraception methods in the U.S. However, recent evidence suggests that the failure rate may be higher than previously reported. We describe women with a history of HS presenting for abortion at a 3-site urban abortion clinic. STUDY DESIGN: Retrospective case series of patients with previous HS who presented to a 3-site urban abortion clinic for pregnancy termination from October 2012 to February 2015. RESULTS: In 28months, 9 patients with prior HS had failure of the method and then an abortion. CONCLUSIONS: This study identifies a number of failures from a setting previously unaccounted. It suggests that perhaps the failure rate is higher than previously reported. The cases here presented, from a 3-site urban abortion clinic over 28months, almost match and sometimes surpass the number of failures reported in multicenter case series in the literature. Surveys of other abortion clinics in the U.S. and elsewhere might also discover other patients whose HS had failed. IMPLICATIONS: We identified a number of hysteroscopic sterilization failures at termination of pregnancy at a 3 site urban abortion clinic. We hypothesize that the HS failure rate underestimates the true method failure because previous analysis have excluded cases such as these. PMID- 27000999 TI - Frequency and correlates of unintended pregnancy risk perceptions. AB - OBJECTIVES: This study is to assess frequency and correlates of women's reports of unintended pregnancy risk in the general population in France. STUDY DESIGN: Data are drawn from the FECOND survey, a national probability survey on sexual and reproductive health conducted in France in 2010. We identified 2969 women ages 15-49years who had heterosexual intercourse in the 4weeks prior to the survey and who were at potential risk of unintended pregnancy. We evaluate women's reports of unintended pregnancy risk in the last 4weeks and identify correlates of such reports using logistic regression modeling. RESULTS: Fifteen percent of women thought that they could have become pregnant in the last 4weeks without wanting to do so. Reports of unintended pregnancy risk were higher among women in very difficult financial situations (OR=1.87 [1.32-2.65]) and foreign born women (OR=1.53 [1.03-2.29]). Exposure in the form of contraceptive practices and errors in use of contraception were the strongest correlates of women's reports of unintended pregnancy risk, yet among the 9.8% of women who reported inconsistent use of contraception or unprotected intercourse in the last 4weeks, 63% did not think they could have become pregnant unintentionally. CONCLUSIONS: Significant discrepancies between pregnancy exposure and women's report of unintended pregnancy risk call for better SRH educational programs to improve pregnancy awareness in the general population. On the other hand, targeted interventions toward women who report being at risk of unintended pregnancy may contribute toward reducing unintended pregnancies given the frequency of such events. PMID- 27001000 TI - Effects of low doses of mifepristone on human embryo implantation process in a three-dimensional human endometrial in vitro co-culture system. AB - OBJECTIVES: We wanted to explore the effects of two different low doses (0.5MUM and 0.05MUM) of mifepristone, exposed during the receptive period, on the human embryo implantation process, using a well-established three-dimensional in vitro cell culture model, specifically developed to study this process. METHODS: An in vitro three-dimensional cell culture model was constructed using human endometrial cells isolated from the endometrium of proven fertile women, collected on cycle day LH+4. After 5 days of culture, supernumerary human embryos were added and cultured for another 5 days with mifepristone 0.5MUM (n=8) or 0.05MUM (n=10) or vehicle as control (n=10). The cultures were checked for embryo attachment and terminated. We studied the expression of 16 reported endometrial receptivity markers in the endometrial constructs using real-time polymerase chain reaction. RESULTS: None of the embryos in 0.5MUM of mifepristone attached to the endometrial constructs (p=.004), whereas 4 out of 10 in 0.05MUM (p=.3698) and 7 out of 10 embryos in the control group attached to the cultures. We found that most of the studied receptivity markers were significantly altered with mifepristone exposure in a similar direction in both treatment groups. Only IL6 was significantly differentially expressed between the treatment groups (p=.017). CONCLUSION: We report for the first time that exposure to a low concentration (0.5MUM) of mifepristone during the receptive period successfully inhibits human embryo implantation process in vitro. Further, we observed a dose-dependent effect of mifepristone on endometrial receptivity at the functional level. IMPLICATION: This study contributes new knowledge that low dose of mifepristone during the short period of receptive phase can inhibit endometrial receptivity, which further promotes mifepristone as a contraceptive agent. This could give women a treatment choice to avoid unwanted pregnancy with high efficacy and minimal side effects. PMID- 27001001 TI - Describing abortion attitudes among young, African American men. AB - OBJECTIVES: This paper describes African American teenaged males' attitudes and perspectives on abortion. METHODS: Data were derived from a larger cross sectional survey of African American males aged 14-19, living in the south side of Chicago. RESULTS: Acceptability of abortion varied by partner type, such that 60% of teenagers felt abortion was acceptable with a casual partner while 37% found it acceptable with committed partners (p<.001). Acceptability also varied by sociocontextual factors, and with overarching uncertainty or inconsistency. CONCLUSIONS: Teenaged African American males have uniquely complex attitudes toward abortion. PMID- 27001002 TI - Hyperglycemia and Inflammatory Property of Circulating Monocytes are Associated with Inflammatory Property of Carotid Plaques in Patients Undergoing Carotid Endarterectomy. AB - AIM: This study aims to determine the association between glucose metabolism and proinflammatory/anti-inflammatory properties of circulating monocytes or those of carotid plaques in patients who underwent carotid endarterectomy. METHODS: Clinical characteristics and expression levels of proinflammatory/anti inflammatory markers in circulating monocytes/carotid plaques were examined in 12 patients with diabetes and 12 patients without diabetes. RESULTS: Circulating monocytes from patients with diabetes revealed higher tumor necrosis factor (TNF) alpha and lower interleukin (IL)-10 expression levels compared with those from patients without diabetes, which was also observed in carotid plaques from patients with diabetes. Hyperglycemia revealed positive and negative correlations with the ratios of IL-6+ and IL-10+ cells in carotid plaques, respectively. Moreover, we determined a positive correlation between circulating monocytes and carotid plaques with respect to TNF-alpha and IL-6 expressions. CONCLUSIONS: The inflammatory property of circulating monocytes was associated with that of carotid plaques. Hyperglycemia increased inflammatory properties and decreased anti-inflammatory properties of carotid plaques. PMID- 27001003 TI - Non-HDL Cholesterol is a More Superior Predictor of Small-Dense LDL Cholesterol than LDL Cholesterol in Japanese Subjects with TG Levels <400 mg/dL. AB - AIM: The Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and treatment of hyperlipidemia in Japanese adults recommend using low-density lipoprotein cholesterol (LDL-C) calculated by Friedewald formula (F_LDL-C) for subjects with triglyceride (TG) levels <400 mg/dL and non-high-density lipoprotein cholesterol (non-HDL-C) levels for subjects with TG levels >=400 mg/dL. Because small-dense LDL particles are more atherogenic than large LDL particles, we sought the better lipid parameter which was more reflective of the high small-dense LDL-C (sdLDL-C) levels in subjects with TG levels <400 mg/dL. METHODS: This study included 769 Japanese subjects who met our inclusion criteria and underwent an annual health examination, including sdLDL-C analyses. RESULTS: The correlation coefficient of non-HDL-C for sdLDL-C (r=0.760) was significantly higher than that of F_LDL-C (r=0.601). The area under the curve (95% confidence interval) was 0.771 (0.731, 0.811) for F_LDL-C and 0.871 (0.842, 0.901) for non HDL-C, which showed significantly higher predictive value for more than fourth quartile value of sdLDL-C (46 mg/dL). The optimal cut-off point of non-HDL-C was 158 mg/dL. Even in subjects stratified by waist circumstance, homeostasis model assessment of insulin resistance, TG, and F_LDL-C levels and non-HDL-C showed stronger relationships with sdLDL-C than F_LDL-C. Moreover, non-HDL-C showed a better relationship with sdLDL-C than total cholesterol (TC), TC/HDL-C, and non HDL-C/HDL-C. CONCLUSION: Our data suggested that non-HDL-C is superior to F_LDL-C and one of the reliable surrogate lipid markers of sdLDL-C in Japanese subjects with TG levels <400 mg/dL. PMID- 27001004 TI - Improvement of Right Ventricular Hemodynamics with Left Ventricular Endocardial Pacing during Cardiac Resynchronization Therapy. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular epicardial (BV-CS) or endocardial left ventricular (LV) stimulation (BV-EN) improves LV hemodynamics. The effect of CRT on right ventricular function is less clear, particularly for BV-EN. Our objective was to compare the simultaneous acute hemodynamic response (AHR) of the right and left ventricles (RV and LV) with BV CS and BV-EN in order to determine the optimal mode of CRT delivery. METHODS: Nine patients with previously implanted CRT devices successfully underwent a temporary pacing study. Pressure wires measured the simultaneous AHR in both ventricles during different pacing protocols. Conventional epicardial CRT was delivered in LV-only (LV-CS) and BV-CS configurations and compared with BV-EN pacing in multiple locations using a roving decapolar catheter. RESULTS: Best BV EN (optimal AHR of all LV endocardial pacing sites) produced a significantly greater RV AHR compared with LV-CS and BV-CS pacing (P < 0.05). RV AHR had a significantly increased standard deviation compared to LV AHR (P < 0.05) with a weak correlation between RV and LV AHR (Spearman rs = -0.06). Compromised biventricular optimization, whereby RV AHR was increased at the expense of a smaller decrease in LV AHR, was achieved in 56% of cases, all with BV-EN pacing. CONCLUSIONS: BV-EN pacing produces significant increases in both LV and RV AHR, above that achievable with conventional epicardial pacing. RV AHR cannot be used as a surrogate for optimizing LV AHR; however, compromised biventricular optimization is possible. The beneficial effect of endocardial LV pacing on RV function may have important clinical benefits beyond conventional CRT. PMID- 27001005 TI - Medical Cannabis Use Is Associated With Decreased Opiate Medication Use in a Retrospective Cross-Sectional Survey of Patients With Chronic Pain. AB - Opioids are commonly used to treat patients with chronic pain (CP), though there is little evidence that they are effective for long term CP treatment. Previous studies reported strong associations between passage of medical cannabis laws and decrease in opioid overdose statewide. Our aim was to examine whether using medical cannabis for CP changed individual patterns of opioid use. Using an online questionnaire, we conducted a cross-sectional retrospective survey of 244 medical cannabis patients with CP who patronized a medical cannabis dispensary in Michigan between November 2013 and February 2015. Data collected included demographic information, changes in opioid use, quality of life, medication classes used, and medication side effects before and after initiation of cannabis usage. Among study participants, medical cannabis use was associated with a 64% decrease in opioid use (n = 118), decreased number and side effects of medications, and an improved quality of life (45%). This study suggests that many CP patients are essentially substituting medical cannabis for opioids and other medications for CP treatment, and finding the benefit and side effect profile of cannabis to be greater than these other classes of medications. More research is needed to validate this finding. PERSPECTIVE: This article suggests that using medical cannabis for CP treatment may benefit some CP patients. The reported improvement in quality of life, better side effect profile, and decreased opioid use should be confirmed by rigorous, longitudinal studies that also assess how CP patients use medical cannabis for pain management. PMID- 27001006 TI - Evolution of photoinduced effects in phase-separated Sm0.5Sr0.5Mn1-yCryO3 thin films. AB - Systematic study on electrical transport properties has been performed in Sm0.5Sr0.5Mn1-yCryO3 thin films illuminated by the light. An evolution of persistent and transient photoinduced effects induced by the impurity doping and temperature has been observed, which is closely related to the number of ferromagnetic clusters. The maximum persistent photoinduced effect is observed at y = 0.08 and the corresponding value is about 61.7% at the power density of 13.7 mW/mm(2). The underlying mechanism can be understood by the coexistence and competition of the multiphases in phase-separated manganites induced by Cr doping. These results would pave the way for practical applications in innovative photoelectric devices of all-oxides. PMID- 27001007 TI - Fetal exposure to tobacco: nicotine and cotinine concentration in amniotic fluid and maternal saliva. AB - OBJECTIVE: Fetal exposure to tobacco constituents is a risk factor for negative birth outcomes. We aimed to determine the relationships between nicotine and cotinine concentrations in amniotic fluid and maternal saliva. METHODS: As part of a therapeutic trial, 42 pregnant smokers agreed to sample amniotic fluid (8 samples from amniocentesis, 34 at birth). Their smoking characteristics were collected along with the newborns' birth outcomes. RESULTS: The median concentrations [IQR] in amniotic fluid and saliva were 11 [7-31] and 38 [7-174] MUg/L for nicotine and 72 [22-123] MUg/L and 55 [17-109] MUg/L for cotinine, respectively. Multivariate models showed that saliva cotinine concentration predicted amniotic fluid nicotine and cotinine concentrations (R2 = 0.398, p < 0.0001 and R2 = 0.708, p < 0.0001 respectively). Amniotic fluid nicotine or cotinine concentration was not associated with birth weight. In multivariate analysis, the time elapsed since the last cigarette was the only variable associated with increased birth weight (R2 = 0.237, p = 0.002). CONCLUSIONS: Maternal saliva sampling for the determination of cotinine concentration is of interest to monitor fetal exposure to nicotine of any origin. Nevertheless, the time elapsed since the last cigarette was a better predictor of birth weight than the biomarkers' concentrations in amniotic fluid or maternal saliva. PMID- 27001008 TI - 'Men at risk': sex work, tourism, and STI/HIV risk in Jamaica. AB - Female sex tourism has become an accepted income generator for many underemployed men in Jamaica who seek to reap economic benefits from relationships with visiting tourist women. This issue provides contexts to explore the numerous ways in which health intersects with issues of masculinity, sexuality and marginality. Based on ethnographic fieldwork in a popular Jamaican resort town, this paper examines the health implications of female sex tourism for the local population and tourist visitors. Data from this project indicate the need for improved sexually transmitted infection education and HIV outreach work towards men who are involved in transactional sex with tourist women. Due to prevalent perceptions of masculinity and gendered notions of sexuality, men who engage in sex tourism constitute a population that rarely receives the attention of local and national health authorities. Data from this qualitative study suggest that engaging this particular vulnerable population could potentially decrease the risk of STI and HIV infection in the country's most popular resort areas. Research of this kind is urgently needed to better understand the risk factors and challenges for Caribbean populations, as well as to inform future prevention efforts in the region. PMID- 27001009 TI - Olmesartan-associated sprue-like enteropathy: know your enemy. PMID- 27001010 TI - Neurological complications and risk factors of cardiopulmonary failure of EV-A71 related hand, foot and mouth disease. AB - From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration >=3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible. PMID- 27001011 TI - NR2A contributes to genesis and propagation of cortical spreading depression in rats. AB - Cortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine. Increasing evidence points to an essential role of NR2A-containing NMDA receptors in CSD propagation in vitro; however, whether these receptors mediate CSD genesis in vivo requires clarification and the role of NR2A on CSD propagation is still under debate. Using in vivo CSD in rats with electrophysiology and in vitro CSD in chick retina with intrinsic optical imaging, we addressed the role of NR2A in CSD. We demonstrated that NVP-AAM077, a potent antagonist for NR2A-containing receptors, perfused through microdialysis probes, markedly reduced cortex susceptibility to CSD, but also reduced magnitude of CSD genesis in rats. Additionally, NVP-AAM077 at 0.3 nmol perfused into the contralateral ventricle, considerably suppressed the magnitude of CSD propagation wave and propagation rate in rats. This reduction in CSD propagation was also observed with TCN-201, a negative allosteric modulator selective for NR2A, at 3 MUM, in the chick retina. Our data provides strong evidence that NR2A subunit contributes to CSD genesis and propagation, suggesting drugs selectively antagonizing NR2A-containing receptors might constitute a highly specific strategy treating CSD associated migraine with a likely better safety profile. PMID- 27001012 TI - Bladder cancer: Atezolizumab effective against advanced-stage disease. PMID- 27001014 TI - Regeneration: Functional kidney progenitors can be isolated from preterm urine. PMID- 27001013 TI - Penile preserving and reconstructive surgery in the management of penile cancer. AB - A major paradigm shift has occurred in the clinical management of penile cancer: the adoption of alternative, less-invasive surgical strategies to address the primary tumour. Such penile-preserving approaches aim to retain aspects of penile function and improve quality of life outcomes by reducing penile alterations and sexual dysfunction incurred by historical surgical approaches without compromising oncological control. Novel options include wide local excision, glansectomy, and glans resurfacing, and these strategies are now included in the spectrum of interventions available to treat penile cancer. Surgical reconstructive techniques have also advanced to include primary closure, closure using skin flaps and grafts, penile lengthening and/or enhancement, and neophalloplasty. All of these options can be readily applied in the risk-informed patient after establishing disease-risk variables and instituting protocols for close surveillance and prompt action for possible disease recurrence. PMID- 27001015 TI - Prostate cancer: Validating early PSA response to enable improved treatment decisions. PMID- 27001017 TI - Systematic review of studies about countertransference in adult psychotherapy. AB - INTRODUCTION: Countertransference, the emotional reaction of a psychotherapist toward a patient, is an important technical element of psychotherapy. The purpose of this systematic review was to identify and describe the main findings of studies that evaluated countertransference in adult psychotherapy. METHODS: A search was conducted of the databases Embase, PubMed, PsycINFO and Web of Knowledge to retrieve data published in any language at any time. RESULTS: Of the 1,081 studies found in the databases, 25 were selected. Most were about psychodynamic psychotherapy, and results indicated that positive countertransference, that is, feelings of closeness to the patient, are associated with positive outcomes, such as symptom improvement and good therapeutic alliance. CONCLUSIONS: Although few studies were found in the literature, countertransference seems to be an important source of knowledge about several aspects, such as treatment outcomes, attachment style, therapeutic alliance, patient symptoms and diagnoses. PMID- 27001016 TI - The implications of ageing and life expectancy in prostate cancer treatment. AB - In patients diagnosed with prostate cancer, the selection of treatment, including the type of therapy and its aggressiveness, is often based on a patient's age and life expectancy. Life expectancy estimates are too often calculated solely on the patient's chronological age, overlooking comorbid conditions and their severity, which can greatly affect life expectancy. If, in addition to chronological age, comorbid conditions are used to assess a patient's life expectancy, the most appropriate treatment options are more likely to be selected. Older, healthy patients might be able to tolerate more aggressive treatment than would be administered on the basis of their age alone, and younger patients with numerous comorbid conditions could avoid harsh therapy that might not be appropriate given their current state of health. The key idea to consider in treatment selection is what a patient's quality of life would be like with or without a particular treatment option. In an era of precision medicine, decisions regarding the provision of health care should be made rationally and on the basis of objective estimates of the threat of disease and the benefits and costs of intervention and within the context of the patient's characteristics and desires. PMID- 27001018 TI - The dialog between psychoanalysis and neuroscience: what does philosophy of mind say? AB - OBJECTIVE: To briefly review how the main monist and dualist currents of philosophy of mind approach the mind-body problem and to describe their association with arguments for and against a closer dialog between psychoanalysis and neuroscience. METHODS: The literature was reviewed for studies in the fields of psychology, psychoanalysis, neuroscience, and philosophy of mind. RESULTS: Some currents are incompatible with a closer dialog between psychoanalysis and neurosciences: interactionism and psychophysical parallelism, because they do not account for current knowledge about the brain; epiphenomenalism, which claims that the mind is a mere byproduct of the brain; and analytical behaviorism, eliminative materialism, reductive materialism and functionalism, because they ignore subjective experiences. In contrast, emergentism claims that mental states are dependent on brain states, but have properties that go beyond the field of neurobiology. CONCLUSIONS: Only emergentism is compatible with a closer dialog between psychoanalysis and neuroscience. PMID- 27001019 TI - Who seeks public treatment for substance abuse in Brazil? Results of a multicenter study involving four Brazilian state capitals. AB - OBJECTIVE: To assess the characteristics of alcohol and drug users who seek treatment at the Brazilian Unified Health System in Brazil. METHOD: A multicenter cross-sectional study involving five clinical and research centers located in four Brazilian state capitals was conducted with 740 in- and outpatients. The only exclusion criterion was the presence of neurological or severe psychiatric symptoms at the moment of the interview. The Addiction Severity Index (ASI-6) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were used to assess the severity of substance use and the problems related. RESULTS: There were significantly more men than women in the sample; mean age was 36 years. The drug most frequently used at all sites was alcohol (78%), followed by cocaine/crack (51%). Alcohol was the drug that most commonly motivated treatment seeking, at all centers. ASI-6 Summary Scores for Recent Functioning (SS-Rs) were quite similar among centers. SS-Rs were compared between users who had never received treatment for psychoactive substance abuse (n = 265, 36.1%) and those who had already been treated at one or more occasions (n = 470, 63.9%). This analysis revealed significant differences between the groups in the drug, psychiatric symptoms, legal, and family/social problems areas (p < 0.05). CONCLUSION: Our findings confirm previous evidence suggesting that the management of patients seeking drug abuse treatment should take several different aspects into consideration, e.g., education, employment, and family relationships, which often appear as areas of concern for these individuals. PMID- 27001020 TI - Emotional dimensions in people with aggressive behavior: differential responses to affective visual stimuli. AB - INTRODUCTION: The emotional interaction between personal attributes and the environment is a key element to understand aggression. This study identified emotional responses of people with different aggressive traits to pictures with a specific affective content. METHODS: Three hundred fifteen individuals were divided into five groups according to their scores on the Buss-Perry Aggression Questionnaire, which consists of 24 pictures of the International Affective Picture System that depict aggression, the suffering of others, filial situations, and sexual content. Each picture was evaluated for valence, arousal, and dominance using the Self-Assessment Manikin scale. RESULTS: Sexual pictures were more appetitive and associated with more arousal in the groups of individuals with some aggression-related dimension than in the non-aggressive group. CONCLUSIONS: A strong interaction was found between aggressive traits (e.g., verbal aggression, physical aggression, anger, and hostility) and pictures with a sexual content. This interaction is decisive in understanding the later phases of aggressive behaviors and sexual aggression. PMID- 27001021 TI - Functioning in early and late stages of schizophrenia. AB - INTRODUCTION: Schizophrenia is frequently associated with a debilitating course and prominent impairment in social and occupational functioning. Although the criteria for classification into stages have not been defined in the literature, illness duration and functioning seem to be good candidates. OBJECTIVE: To compare functioning of patients with schizophrenia at different stages of the disease (early vs. late) and healthy sex- and age-matched controls. METHODS: This double-blinded, case-controlled study included 79 individuals: 23 patients with schizophrenia diagnosed up to 5 years earlier; 19 patients with schizophrenia diagnosed at least 20 years earlier; and healthy matched controls. Diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I Disorder. Functioning was assessed using the Functioning Assessment Short Test (FAST). RESULTS: Patients in the early stage had significantly higher scores than healthy controls in total FAST and in autonomy, occupational functioning, cognitive functioning and interpersonal relationships. Individuals in the late stage had significantly poorer functioning than controls in all domains. The comparison of functioning between the two groups of patients revealed no significant differences, except in occupational functioning, in which late stage patients had a poorer performance. CONCLUSION: Functioning impairment in schizophrenia tends to remain stable despite illness duration. Therefore, functioning should be effectively assessed at an early stage, as illness duration alone may not be the most reliable criterion to stage patients with schizophrenia. PMID- 27001022 TI - Translation and cross-cultural adaptation of the Temperament & Personality Questionnaire into Brazilian Portuguese. AB - INTRODUCTION: The Temperament & Personality Questionnaire (T&P) is a self-report instrument designed to evaluate personality styles overrepresented in patients with depression. This report briefly describes the translation and adaptation of the T&P into Brazilian Portuguese. METHODS: The procedures, which included 10 steps, followed guidelines for the adaptation of self-report instruments defined by the International Society For Pharmacoeconomics and Outcomes Research (ISPOR) Task Force for Translation and Cultural Adaptation. RESULTS: The author of the original T&P questionnaire authorized and participated in the translation conducted by the authors and independent native speakers. Evaluation of the translated questionnaire indicated that only minor adjustments were required in the Portuguese version. CONCLUSIONS: The Brazilian version of T&P, translated and adapted following a rigid standardized process, is available for use free of charge and may be especially useful in pursuing links between personality styles and depressive conditions. PMID- 27001023 TI - Emotional impact of halitosis. AB - OBJECTIVE: To evaluate the emotional impact of halitosis on 18-year-old men using a self-reported questionnaire. METHOD: A total of 2,224 participants underwent dental and medical examinations in the army medical services in the city of Pelotas, southern Brazil, in July 2008. RESULTS: In this sample, 12% of respondents expressed concern about their oral malodor, which had a strong emotional impact on their quality of life. CONCLUSIONS: The individuals reporting halitosis showed a higher degree of concern with their oral malodor. Low educational level and low income were associated with psychological impact and halitosis in this population. PMID- 27001025 TI - Correction to "On the Covalent Character of Rare Gas Bonding Interactions: A New Kind of Weak Interaction". PMID- 27001024 TI - Novel autophosphorylation sites of Src family kinases regulate kinase activity and SH2 domain-binding capacity. AB - Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the C-terminal site to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain. PMID- 27001026 TI - Fathers' experiences of living with cancer: a phenomenological study. AB - There is a paucity of knowledge about fathers' experiences of cancer. This study explored the experiences of fathers diagnosed and living with cancer while also having parental responsibility for children. A hermeneutic phenomenological approach guided the study. Data were generated through 22 in-depth interviews with 10 fathers throughout Northern Ireland. The findings evidenced that fathers' identities are challenged and frequently re-shaped by the cancer experience, in many cases leading to an improved lifestyle behaviour. Heightened engagement with their children can provide a protective effect from the illness. On the other hand a lack of involvement led to frustration and low mood. The findings also demonstrated that father/child relationships were adversely affected by the social complexities that exist in the variances and diversity of fathers parenting roles and status. This knowledge contributes to our understanding of the complex relationships of fathers in non-traditional roles. It extends our understanding of how, when stereotyped gendered roles are ascribed to fathers it can impact on a fathers' ability to fulfil the traditional breadwinner's role. This is knowledge that will inform health care professionals and enable them to provide gendered-sensitive care that takes account of the masculine psychological responses that can shape the cancer experience. PMID- 27001027 TI - Intermuscular force transmission along myofascial chains: a systematic review. AB - The present review aims to provide a systematic overview on tensile transmission along myofascial chains based on anatomical dissection studies and in vivo experiments. Evidence for the existence of myofascial chains is growing, and the capability of force transmission via myofascial chains has been hypothesized. However, there is still a lack of evidence concerning the functional significance and capability for force transfer. A systematic literature research was conducted using MEDLINE (Pubmed), ScienceDirect and Google Scholar. Studied myofascial chains encompassed the superficial backline (SBL), the back functional line (BFL) and the front functional line (FFL). Peer-reviewed human dissection studies as well as in vivo experiments reporting intermuscular tension transfer between the constituents of a myofascial chain were included. To assess methodic quality, two independent investigators rated studies by means of validated assessment tools (QUACS and PEDro Scale). The literature research identified 1022 articles. Nine studies (moderate to excellent methodological quality) were included. Concerning the SBL and the BFL, there is moderate evidence for force transfer at all three transitions (based on six studies), and one of two transitions (three studies). One study yields moderate evidence for a slight, but not significant force transfer at one transition in the FFL. The findings of the present study indicate that tension can be transferred between some of the examined adjacent structures. Force transfer might have an impact in overuse conditions as well as on sports performance. However, different methods of force application and measurement hinder the comparability of results. Considering anatomical variations in the degree of continuity and histological differences of the linking structures is crucial for interpretation. Future studies should focus on the in vivo function of myofascial continuity during isolated active or passive tissue tensioning. PMID- 27001028 TI - NMR-metabolomics profiling of mammary gland secretory tissue and milk serum in two goat breeds with different levels of tolerance to seasonal weight loss. AB - Goats are of special importance in the Mediterranean and tropical regions for producing a variety of dairy products. The scarcity of pastures during the dry season leads to seasonal weight loss (SWL), which affects milk production. In this work, we studied the effect of feed-restriction on two dairy goat breeds, with different tolerance levels to SWL: the Majorera breed (tolerant) and the Palmera breed (susceptible). Nuclear magnetic resonance (NMR) was used to compare the metabolome of an aqueous fraction of the mammary gland and milk serum from both breeds. Goats in mid-lactation were divided by breed, and each in two feed regime groups: the control group and the restricted-fed group (to achieve 15-20% reduction of body weight at the end of the experiment). Milk and mammary gland samples were collected at the end of the experimental period (23rd day). (1)H NMR spectra were collected from the aqueous extract of the mammary gland biopsies and the milk serum. Profiling analysis has led to the identification of 46 metabolites in the aqueous extract of the mammary gland. Lactose, glutamate, glycine and lactate were found to be the most abundant. Analysis of milk serum allowed the identification of 50 metabolites, the most abundant being lactose, citrate and creatine. Significant differences were observed, in mammary gland biopsies and milk serum, between control and restricted-fed groups in both breeds, albeit with no differences between the breeds. Variations seem to be related to metabolism adaptation to the low-energy diet and are indicative of breed-specific microflora. Milk serum showed more metabolites varying between control and restricted groups, than the mammary gland. The Majorera breed also showed more variations than the Palmera breed in milk samples, which could be an indication of a prompt adaptation to SWL by the Majorera breed. PMID- 27001029 TI - Similar exemplar pooling processes underlie the learning of facial identity and handwriting style: Evidence from typical observers and individuals with Autism. AB - Considerable research has addressed whether the cognitive and neural representations recruited by faces are similar to those engaged by other types of visual stimuli. For example, research has examined the extent to which objects of expertise recruit holistic representation and engage the fusiform face area. Little is known, however, about the domain-specificity of the exemplar pooling processes thought to underlie the acquisition of familiarity with particular facial identities. In the present study we sought to compare observers' ability to learn facial identities and handwriting styles from exposure to multiple exemplars. Crucially, while handwritten words and faces differ considerably in their topographic form, both learning tasks share a common exemplar pooling component. In our first experiment, we find that typical observers' ability to learn facial identities and handwriting styles from exposure to multiple exemplars correlates closely. In our second experiment, we show that observers with Autism Spectrum Disorder (ASD) are impaired at both learning tasks. Our findings suggest that similar exemplar pooling processes are recruited when learning facial identities and handwriting styles. Models of exemplar pooling originally developed to explain face learning, may therefore offer valuable insights into exemplar pooling across a range of domains, extending beyond faces. Aberrant exemplar pooling, possibly resulting from structural differences in the inferior longitudinal fasciculus, may underlie difficulties recognising familiar faces often experienced by individuals with ASD, and leave observers overly reliant on local details present in particular exemplars. PMID- 27001030 TI - Plasticity in leaf-level water relations of tropical rainforest trees in response to experimental drought. AB - The tropics are predicted to become warmer and drier, and understanding the sensitivity of tree species to drought is important for characterizing the risk to forests of climate change. This study makes use of a long-term drought experiment in the Amazon rainforest to evaluate the role of leaf-level water relations, leaf anatomy and their plasticity in response to drought in six tree genera. The variables (osmotic potential at full turgor, turgor loss point, capacitance, elastic modulus, relative water content and saturated water content) were compared between seasons and between plots (control and through-fall exclusion) enabling a comparison between short- and long-term plasticity in traits. Leaf anatomical traits were correlated with water relation parameters to determine whether water relations differed among tissues. The key findings were: osmotic adjustment occurred in response to the long-term drought treatment; species resistant to drought stress showed less osmotic adjustment than drought sensitive species; and water relation traits were correlated with tissue properties, especially the thickness of the abaxial epidermis and the spongy mesophyll. These findings demonstrate that cell-level water relation traits can acclimate to long-term water stress, and highlight the limitations of extrapolating the results of short-term studies to temporal scales associated with climate change. PMID- 27001032 TI - Retention costs of periodontally compromised molars in a German population. AB - AIM: This study assessed the long-term costs per retention year for periodontally affected molars. METHODS: A cohort of 379 compliant subjects was retrospectively evaluated. Periodontal, restorative, endodontic, prosthetic and surgical treatment costs were estimated based on fee items of the private German health insurance. Costs/year were calculated and the impact of tooth- and subject related factors on this cost-effectiveness ratio assessed using generalized linear-mixed modelling. RESULTS: 2306 molars received non-regenerative initial and supportive therapy and were followed until extraction or censoring (in mean (SD): 16.5 [6.8] years). Per year, 0.07 (SD: 0.12) deep scalings, 0.04 (0.11) open flap debridements, 0.01 (0.04) resective therapies and 2.49 (0.12) SPTs had been provided. Few teeth received non-periodontal treatments. Costs/year decreased significantly with each tooth a patient had at baseline (mean difference: -0.01, 95% CI: -0.02/-0.01 Euro/year), and increased with each mm of probing-pocket depth (0.04 [0.03/0.06] Euro/year), in upper (0.07 [0.11/0.31] Euro/year) or mobile molars (up to 0.33 [0.18/0.48] Euro/year), those with bone loss (up to 0.11 [0.04/0.17] Euro/year), endodontic treatment (0.24 [0.15/0.33] Euro/year), peri-apical lesions (0.24 [0.11/0.38]) and prosthetic treatment (0.54 [0.49/0.59] Euro/year). CONCLUSIONS: Annual costs for retaining periodontally affected molars were limited, and associated mainly with tooth-level factors. PMID- 27001031 TI - Pediatric liver transplantation: predictors of survival and resource utilization. AB - PURPOSE: We sought to identify factors associated with increased resource utilization and in-hospital mortality for pediatric liver transplantation (LT). METHODS: Kids' Inpatient Database (1997-2009) was used to identify cases of LT in patients <20 years old. RESULTS: Overall, 2905 cases were identified, with an in hospital survival of 91 %. LT was performed most frequently in < 5 year olds (61 %), females (51 %), and Caucasians (56 %). LT was performed at urban teaching hospitals (97 %) and facilities with children's units (51 %). Indications included pathologic conditions of the biliary tract (44 %) and inborn errors of metabolism (34 %), though unspecified end stage liver disease was the most common (75 %). Logistic regression found higher mortality in children undergoing LT for malignant conditions (odds ratio: 4.8) and acute hepatic failure (OR 3.4). Cases complicated by renal failure (OR 7.7) and complications of LT (OR 2.7) had higher mortality rates. Resource utilization increased for children with renal failure and those with hemorrhage as a complication of LT, p < 0.05. CONCLUSION: Hospital survival is predicted by indication and complications associated with LT. Resource utilization increased with renal failure and complications related to LT. Admission length was sensitive to payer status, hospital characteristics, and UNOS region, whereas total costs were unaffected by payer status or hospital type. PMID- 27001033 TI - Rpb1 foot mutations demonstrate a major role of Rpb4 in mRNA stability during stress situations in yeast. AB - The RPB1 mutants in the foot region of RNA polymerase II affect the assembly of the complex by altering the correct association of both the Rpb6 and the Rpb4/7 dimer. Assembly defects alter both transcriptional activity as well as the amount of enzyme associated with genes. Here, we show that the global transcriptional analysis of foot mutants reveals the activation of an environmental stress response (ESR), which occurs at a permissive temperature under optimal growth conditions. Our data indicate that the ESR that occurs in foot mutants depends mostly on a global post-transcriptional regulation mechanism which, in turn, depends on Rpb4-mRNA imprinting. Under optimal growth conditions, we propose that Rpb4 serves as a key to globally modulate mRNA stability as well as to coordinate transcription and decay. Overall, our results imply that post-transcriptional regulation plays a major role in controlling the ESR at both the transcription and mRNA decay levels. PMID- 27001034 TI - Methods to induce labour: a systematic review, network meta-analysis and cost effectiveness analysis. AB - OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of labour induction methods. METHODS: We conducted a systematic review of randomised trials comparing interventions for third-trimester labour induction (search date: March 2014). Network meta-analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision-tree model from a UK NHS perspective and calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit, and cost-effectiveness acceptability curves. MAIN RESULTS: In all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (>=50 MUg) were most likely to achieve VD24. Titrated low-dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (>=50 MUg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra-amniotic prostaglandin E2 reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost-effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low-dose) misoprostol showed the highest probability of being most cost-effective. CONCLUSIONS: Future trials should be designed and powered to detect a method that is more cost-effective than low-dose titrated oral misoprostol. TWEETABLE ABSTRACT: New study ranks methods to induce labour in pregnant women on effectiveness and cost. PMID- 27001035 TI - Incidence and management of inadvertent puncture and sheath placement in the aorta during attempted transseptal puncture. AB - Aims: Transseptal punctures (TSP) are routinely performed in cardiac interventions requiring access to the left heart. While pericardial effusion/tamponade are well-recognized complications, few data exist on accidental puncture of the aorta and its management and outcome. We therefore analysed our single centre database for this complication. Methods and results: We assessed frequency and outcome of inadvertent aortic puncture during TSP in consecutive patients undergoing ablation procedures between January 2005 and December 2014. During the 10-year period, two inadvertent aortic punctures occurred among 2936 consecutive patients undergoing 4305 TSP (0.07% of patients, 0.05% of TSP) and in one Mustard patient during attempted baffle puncture. The first two patients required left ventricular access for catheter ablation of ventricular tachycardia. In both cases, an 11.5F steerable sheath (inner diameter 8.5F) was accidentally placed in the ascending aorta just above the aortic valve. In the presence of surgical standby, the sheaths were pulled back with a wire left in the aorta. Under careful haemodynamic and echocardiographic observation, this wire was also pulled back 30 min later. None of the patients required a closing device or open heart surgery. None of the patients suffered complications from the accidental aortic puncture and sheath placement. Conclusion: Inadvertent aortic puncture and sheath placement are rare complications in patients undergoing TSP for interventional procedures. Leaving a guidewire in place during the observation period may allow introduction of sheaths or other tools in order to control haemodynamic deterioration. PMID- 27001036 TI - Ratchet syndrome in complex congenital heart disease. PMID- 27001037 TI - Multipolar ablation for atrial fibrillation: are we going in circles? PMID- 27001040 TI - Soft drink makers consider legal challenge against sugar tax. PMID- 27001041 TI - Revisiting Bangham's law of adsorption-induced deformation: changes of surface energy and surface stress. AB - When fluids are adsorbed on a solid surface they induce noticeable stresses, which cause the deformation of the solid. D. H. Bangham and co-authors performed a series of experimental measurements of adsorption-induced strains, and concluded that physisorption causes expansion, which is proportional to the lowering of the surface energy Deltagamma. This statement is referred to as the Bangham effect or Bangham's law. However, it is known that the quantity that controls the deformation is actually the change in surface stress Deltaf rather than surface energy Deltagamma, but this difference has not been considered in the context of adsorption-induced deformation of mesoporous materials. We use the Brunauer-Emmett-Teller (BET) theory to derive both values and show the difference between them. We find the condition when the difference between the two vanishes, and Bangham's law is applicable; it is likely that this condition is satisfied in most cases, and prediction of strain based on Deltagamma is a good approximation. We show that this is the case for adsorption of argon and water on Vycor glass. Finally, we show that the difference between Deltagamma and Deltaf can explain some of the experimental data that contradicts Bangham's law. PMID- 27001042 TI - Osmolarity: A hidden factor in Nanotoxicology. AB - In the field of drug delivery, long circulating nanocarriers in the blood have many advantages such as targeted drug delivery and sustained release. Based on our current knowledge, evaluation of the effect of long circulating nanocarriers in the blood stream on osmolarity of plasma has not been reported before. In this study, osmotic pressure developed by some commercially available nanocarriers was estimated based on Van't Hoff equation. It is noteworthy that theoretically, nanocarriers do not have any significant effect on osmolarity of plasma. However, it is worth being evaluated experimentally in order to be taken into account in future studies. PMID- 27001044 TI - Use of healthcare services in the region of origin among patients with an immigrant background in Denmark: a qualitative study of the motives. AB - BACKGROUND: In Denmark, immigrants have been found to have a higher use of healthcare services abroad. Since this use may have an impact on both the individual patient and the healthcare system in the country of residence, research into underlying reasons is of increasing relevance. This study therefore investigates what motives patients with an immigrant background have for seeking healthcare services in their region of origin. METHODS: The study was based on 10 semi-structured interviews with 10 patients who had an immigrant background, primarily originating from Turkey and the Middle East, recruited at a clinic of immigrant medicine in Denmark. The interviews were analysed thematically to elucidate motives for seeking healthcare services abroad, with focus on identifying push and pull factors. RESULTS: Four motives for seeking healthcare in the region of origin were salient in the material: the perception of availability, in terms of quantity and access; familiarity, conceptualised as feeling comfortable within the healthcare system; perception of quality of services; and finally, the perceived need for a second opinion. All motives emerged simultaneously as push factors, motivating immigrants to explore healthcare services abroad, and pull factors, attracting them to their country of origin. Affordability did not emerge as an independent motive but influenced the other factors. CONCLUSION: The use of healthcare services abroad by patients with an immigrant background constitutes active health-seeking behaviours shaped by a range of factors perceived to be limiting access to high-quality services in Denmark. Further research, including quantitative studies, should be initiated to investigate the importance of these motives among larger, more diverse immigrant groups, consequences for treatment regimes, and the healthcare professionals' perspective on the use of healthcare in the region of origin among immigrant patients. PMID- 27001043 TI - Abiraterone acetate in metastatic castration-resistant prostate cancer - the unanticipated real-world clinical experience. AB - BACKGROUND: There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real life clinical practice. METHODS: The clinical records of mCRPC patients treated with AA from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. The treatment efficacy and its determinants, and toxicities were determined. RESULTS: A total of 110 patients with mCRPC were treated with AA in the review period, of whom 58 were chemo-naive and 52 had received prior chemotherapy (post-chemo). The median follow-up time was 7.5/11.4 months for chemo-naive/post-chemo patients. 6.9/15.4 % of chemo-naive/post-chemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 18.1/15.5 months and 6.7/6.4 months for chemo-naive/post-chemo patients, respectively. Among chemo-naive patients, those with visceral diseases had significantly inferior OS (2.8 vs 18.0 p = 0.0007) and PFS (2.8 vs 6.8 months, p = 0.0088) than those without. Pain control was comparable in both groups of patients. The most common grade 3 or above toxicities were hypertension (6.9/5.8 %) and hypokalemia (3.4/3.8 %) in chemo naive/post-chemo patients. In multivariate analysis, the presence of prostate specific antigen (PSA) response (>=50 % drop of PSA from baseline) within the first 3 months of therapy was associated with favorable OS and PFS in both chemo naive and post-chemo group. CONCLUSIONS: In clinical practice outside the trial setting, OS after AA in our chemo-naive patient cohort (18.1 months) was considerably shorter than that reported in the COU-AA-302 trial (34.7 months), and the OS was particularly short in those with visceral metastases (2.8 months). Conversely, AA was efficacious in post-chemo patients. AA resulted in comparable pain control in both groups of patients. The presence of PSA response within the first 3 months of treatment was a significant determinant of survival. PMID- 27001045 TI - Socioeconomic Inequality in mortality using 12-year follow-up data from nationally representative surveys in South Korea. AB - BACKGROUND: Investigations into socioeconomic inequalities in mortality have rarely used long-term mortality follow-up data from nationally representative samples in Asian countries. A limited subset of indicators for socioeconomic position was employed in prior studies on socioeconomic inequalities in mortality. We examined socioeconomic inequalities in mortality using follow-up 12 year mortality data from nationally representative samples of South Koreans. METHODS: A total of 10,137 individuals who took part in the 1998 and 2001 Korea National Health and Nutrition Examination Surveys were linked to mortality data from Statistics Korea. Of those individuals, 1,219 (12.1 %) had died as of December 2012. Cox proportional hazard models were used to estimate the relative risks of mortality according to a wide range of socioeconomic position (SEP) indicators after taking into account primary sampling units, stratification, and sample weights. RESULTS: Our analysis showed strong evidence that individuals with disadvantaged SEP indicators had greater all-cause mortality risks than their counterparts. The magnitude of the association varied according to gender, age group, and specific SEP indicators. Cause-specific analyses using equivalized income quintiles showed that the magnitude of mortality inequalities tended to be greater for cardiovascular disease and external causes than for cancer. CONCLUSION: Inequalities in mortality exist in every aspect of SEP indicators, both genders, and age groups, and four broad causes of deaths. The South Korean economic development, previously described as effective in both economic growth and relatively equitable income distribution, should be scrutinized regarding its impact on socioeconomic mortality inequalities. Policy measures to reduce inequalities in mortality should be implemented in South Korea. PMID- 27001048 TI - Psychiatry and terrorism: exploring the unacceptable. PMID- 27001047 TI - Clinical Evaluation of a Fully-automatic Segmentation Method for Longitudinal Brain Tumor Volumetry. AB - Information about the size of a tumor and its temporal evolution is needed for diagnosis as well as treatment of brain tumor patients. The aim of the study was to investigate the potential of a fully-automatic segmentation method, called BraTumIA, for longitudinal brain tumor volumetry by comparing the automatically estimated volumes with ground truth data acquired via manual segmentation. Longitudinal Magnetic Resonance (MR) Imaging data of 14 patients with newly diagnosed glioblastoma encompassing 64 MR acquisitions, ranging from preoperative up to 12 month follow-up images, was analysed. Manual segmentation was performed by two human raters. Strong correlations (R = 0.83-0.96, p < 0.001) were observed between volumetric estimates of BraTumIA and of each of the human raters for the contrast-enhancing (CET) and non-enhancing T2-hyperintense tumor compartments (NCE-T2). A quantitative analysis of the inter-rater disagreement showed that the disagreement between BraTumIA and each of the human raters was comparable to the disagreement between the human raters. In summary, BraTumIA generated volumetric trend curves of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments comparable to estimates of human raters. These findings suggest the potential of automated longitudinal tumor segmentation to substitute manual volumetric follow-up of contrast-enhancing and non-enhancing T2-hyperintense tumor compartments. PMID- 27001046 TI - Identification of a mismatch-specific endonuclease in hyperthermophilic Archaea. AB - The common mismatch repair system processed by MutS and MutL and their homologs was identified in Bacteria and Eukarya. However, no evidence of a functional MutS/L homolog has been reported for archaeal organisms, and it is not known whether the mismatch repair system is conserved in Archaea. Here, we describe an endonuclease that cleaves double-stranded DNA containing a mismatched base pair, from the hyperthermophilic archaeon Pyrococcus furiosus The corresponding gene revealed that the activity originates from PF0012, and we named this enzyme Endonuclease MS (EndoMS) as the mismatch-specific Endonuclease. The sequence similarity suggested that EndoMS is the ortholog of NucS isolated from Pyrococcus abyssi, published previously. Biochemical characterizations of the EndoMS homolog from Thermococcus kodakarensis clearly showed that EndoMS specifically cleaves both strands of double-stranded DNA into 5'-protruding forms, with the mismatched base pair in the central position. EndoMS cleaves G/T, G/G, T/T, T/C and A/G mismatches, with a more preference for G/T, G/G and T/T, but has very little or no effect on C/C, A/C and A/A mismatches. The discovery of this endonuclease suggests the existence of a novel mismatch repair process, initiated by the double-strand break generated by the EndoMS endonuclease, in Archaea and some Bacteria. PMID- 27001049 TI - Computational modeling approaches to the dynamics of oncolytic viruses. AB - Replicating oncolytic viruses represent a promising treatment approach against cancer, specifically targeting the tumor cells. Significant progress has been made through experimental and clinical studies. Besides these approaches, however, mathematical models can be useful when analyzing the dynamics of virus spread through tumors, because the interactions between a growing tumor and a replicating virus are complex and nonlinear, making them difficult to understand by experimentation alone. Mathematical models have provided significant biological insight into the field of virus dynamics, and similar approaches can be adopted to study oncolytic viruses. The review discusses this approach and highlights some of the challenges that need to be overcome in order to build mathematical and computation models that are clinically predictive. WIREs Syst Biol Med 2016, 8:242-252. doi: 10.1002/wsbm.1332 For further resources related to this article, please visit the WIREs website. PMID- 27001050 TI - Statistics in molecular modeling: a summary. PMID- 27001051 TI - Efficient Transduction of Corneal Stroma by Adeno-Associated Viral Serotype Vectors for Implications in Gene Therapy of Corneal Diseases. AB - Corneal disease is one of the leading causes of blindness worldwide. Gene therapy is an attractive therapeutic strategy for corneal diseases, but currently underdeveloped. Recombinant adeno-associated viral (rAAV) vectors have emerged as a highly promising gene therapy platform. This study aims to identify rAAV vectors that can efficiently transduce corneal stroma for potential applications in studying pathophysiology of corneal diseases and therapeutic development. We characterized 14 rAAV serotypes expressing enhanced green fluorescent protein (EGFP), for cell specificity and transduction efficiency after either intrastromal injection or topical administration in mouse corneas in vivo. Our results show that intrastromal injections of rAAVrh.8, rAAVrh.10, rAAVrh.39, and rAAVrh.43 efficiently transduce mouse corneal stroma in vivo, and that topical administrations of rAAVrh.10 and rAAVrh.39 subsequent to epithelial scraping generate detectable transgene expression. In vivo imaging analysis revealed that transgene expression became detectable by 1 week postadministration, peaked at 2 weeks, and lasted for the duration of the study (i.e., 4 weeks). Both rAAVrh.10 and rAAVrh.39 transduced more than 50% of keratocytes, the major cell type in the corneal stroma, by intrastromal injection and 30% by topical administration. Histopathology indicated that rAAV transduction of cornea caused no morphological adverse effects. Overall, our findings suggest that some rAAV serotype vectors can efficiently transduce corneal stroma in vivo, constituting a potentially powerful and safe gene delivery platform for gene therapy of corneal diseases. PMID- 27001052 TI - Copy number variations and genome-wide associations reveal putative genes and metabolic pathways involved with the feed conversion ratio in beef cattle. AB - The use of genome-wide association results combined with other genomic approaches may uncover genes and metabolic pathways related to complex traits. In this study, the phenotypic and genotypic data of 1475 Nellore (Bos indicus) cattle and 941,033 single nucleotide polymorphisms (SNPs) were used for genome-wide association study (GWAS) and copy number variations (CNVs) analysis in order to identify candidate genes and putative pathways involved with the feed conversion ratio (FCR). The GWAS was based on the Bayes B approach analyzing genomic windows with multiple regression models to estimate the proportion of genetic variance explained by each window. The CNVs were detected with PennCNV software using the log R ratio and B allele frequency data. CNV regions (CNVRs) were identified with CNVRuler and a linear regression was used to associate CNVRs and the FCR. Functional annotation of associated genomic regions was performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID) and the metabolic pathways were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG). We showed five genomic windows distributed over chromosomes 4, 6, 7, 8, and 24 that explain 12 % of the total genetic variance for FCR, and detected 12 CNVRs (chromosomes 1, 5, 7, 10, and 12) significantly associated [false discovery rate (FDR) < 0.05] with the FCR. Significant genomic regions (GWAS and CNV) harbor candidate genes involved in pathways related to energetic, lipid, and protein metabolism. The metabolic pathways found in this study are related to processes directly connected to feed efficiency in beef cattle. It was observed that, even though different genomic regions and genes were found between the two approaches (GWAS and CNV), the metabolic processes covered were related to each other. Therefore, a combination of the approaches complement each other and lead to a better understanding of the FCR. PMID- 27001054 TI - Incidence of contrast-induced acute kidney injury in a pediatric setting: a cohort study. AB - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a common pathology among adult patients, with an incidence ranging from 3-25 % depending on risk factors. Little information is available regarding CI-AKI incidence, risk factors, and prognostic impact in the pediatric population. METHODS: We performed a retrospective study of pediatric patients who underwent computed tomography (CT) scan with iodinated contrast media injection between 2005 and 2014 in five pediatric units of a university hospital. CI-AKI was defined according to Kidney Disease/Improving Global Outcomes (KDIGO) criteria. RESULTS: Of 346 identified patients, 233 had renal function follow-up and were included in our analyses. CI AKI incidence was 10.3 % [95 % confidence interval (CI) 6.4-14.2 %]. CI-AKI was associated with 30-day unfavorable outcome before (45.8 % vs. 19.7 %, P = 0.007) and after [odds ratio (OR) 3.6; 95 % CI 1.4-9.5] adjustment for confounders. No independent risk factors of CI-AKI were identified. CONCLUSIONS: CI-AKI incidence was as high as 10.3 % following intravenous contrast media administration in the pediatric setting. As reported among adults, CI-AKI was associated with unfavorable outcome after adjustment for confounders. Although additional studies are needed in the pediatric setting, our data suggest that physicians should maintain a high degree of suspicion toward this complication among pediatric patients. PMID- 27001053 TI - Role of renal sympathetic nerve activity in prenatal programming of hypertension. AB - Prenatal insults, such as maternal dietary protein deprivation and uteroplacental insufficiency, lead to small for gestational age (SGA) neonates. Epidemiological studies from many different parts of the world have shown that SGA neonates are at increased risk for hypertension and early death from cardiovascular disease as adults. Animal models, including prenatal administration of dexamethasone, uterine artery ligation and maternal dietary protein restriction, result in SGA neonates with fewer nephrons than controls. These models are discussed in this educational review, which provides evidence that prenatal insults lead to altered sodium transport in multiple nephron segments. The factors that could result in increased sodium transport are discussed, focusing on new information that there is increased renal sympathetic nerve activity that may be responsible for augmented renal tubular sodium transport. Renal denervation abrogates the hypertension in programmed rats but has no effect on control rats. Other potential factors that could cause hypertension in programmed rats, such as the renin-angiotensin system, are also discussed. PMID- 27001055 TI - [Current therapy of polyarticular forms of juvenile idiopathic arthritis]. AB - Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in infancy and childhood. Approximately 20 % of patients with JIA suffer from the polyarticular form of the disease, which causes a substantial disease burden and long-term sequelae. Therapeutic approaches have used steroids and conventional disease modifying antirheumatic drugs (DMARD) but over the last decade new drugs have become available for the treatment of JIA, in particular biologic DMARD. This article summarizes the current therapy options for polyarticular JIA. PMID- 27001056 TI - Recruitment of osteogenic cells to bone formation sites during development and fracture repair. AB - Recruitment of osteoblast lineage cells to their bone-forming locations is essential for skeletal development and fracture healing. In developing bones, osteoprogenitor cells invade the cartilage mold to establish the primary ossification center. Similarly, osteogenic cells infiltrate and populate the callus tissue that is formed following an injury. Proper bone development and successful fracture repair must, therefore, rely on controlled temporal and spatial navigation cues guiding the cells to the sites where new bone formation is needed. Some cellular mechanisms and molecular pathways involved have been elucidated. PMID- 27001057 TI - Pneumococcal meningitis: clinical-pathological correlations (MeninGene-Path). AB - Pneumococcal meningitis is associated with substantial mortality and morbidity. We systematically assessed brain histopathology of 31 patients who died of pneumococcal meningitis from a nationwide study (median age 67 years; 21 (67 %) were male) using a pathology score including inflammation and vascular damage. Of the 27 patients with known time from the admission to death, 14 patients died within 7 days of admission and 13 after 7 days of admission. Eleven of 25 (44 %) patients had been treated with adjunctive dexamethasone therapy. Observed pathological processes were inflammation of medium-large arteries in 30 brains (97 %), cerebral haemorrhage in 24 (77 %), cerebritis in 24 (77 %), thrombosis in 21 (68 %), infarction in 19 (61 %) and ventriculitis in 19 (of 28 cases, 68 %). Inflammation of medium-large arteries led to obstruction of the vascular lumen in 14 (of 31 cases, 45 %). Vascular inflammation was associated with infarction and thrombosis of brain parenchymal vessels. Hippocampal dentate gyrus apoptosis between patients treated with and without dexamethasone was similar (p = 0.66); however, dexamethasone treated patients had higher total pathology score than non dexamethasone treated patients (p = 0.003). Our study shows that vascular damage is key in the process of brain damage in pneumococcal meningitis. Data and material of this study will be made open-access for translational research in pneumococcal meningitis (MeninGene-Path). PMID- 27001058 TI - Evolution of East Asia's Arcto-Tertiary relict Euptelea (Eupteleaceae) shaped by Late Neogene vicariance and Quaternary climate change. AB - BACKGROUND: The evolutionary origin and historical demography of extant Arcto Tertiary forest species in East Asia is still poorly understood. Here, we reconstructed the evolutionary and population demographic history of the two extant Euptelea species in China (E. pleiosperma) and Japan (E. polyandra). Chloroplast/nuclear DNA sequences and microsatellite loci were obtained from 36 Euptelea populations to explore molecular structure and diversity in relation to past and present distributions based on ecological niche modelling (ENM). Time calibrated phylogenetic/phylogeographic inferences and niche-identity tests were used to infer the historical process of lineage formation. RESULTS: Euptelea pleiosperma diverged from E. polyandra around the Late Miocene and experienced significant ecological differentiation. A near-simultaneous diversification of six phylogroups occurred during the mid-to-late Pliocene, in response to the abrupt uplift of the eastern Tibetan Plateau and an increasingly cooler and drier climate. Populations of E. pleiosperma seem to have been mostly stationary through the last glacial cycles, while those of E. polyandra reflect more recent climate-induced cycles of range contraction and expansion. CONCLUSIONS: Our results illustrate how Late Neogene climatic/tectonic changes promoted speciation and lineage diversification in East Asia's Tertiary relict flora. They also demonstrate for the first time a greater variation in such species' responses to glacial cycles in Japan when compared to congeners in China. PMID- 27001059 TI - A Proteomic Analysis of Human Uterine Myoma. AB - Uterine leiomyoma is a benign smooth muscle tumor characterized by a high incidence in women of reproductive age. The aetiology of this tumor is still unknown but established risk factors include high levels of female hormones, family history, African ancestry, early age of menarche and obesity. Here, to identify proteomic features associated with this tumor type, we performed a liquid chromatography-mass spectrometry (LC-MS/MS) analysis of uterine myomas. The identified proteins were subjected to a gene ontology analysis to generate biological functions, molecular processes, and protein networks that were relevant to the uploaded dataset. Pathway-based analysis was an effective approach to investigate the molecular mechanisms underlying the disease and to create biological hypotheses about regulation of our proteins including the identification of upstream regulators and main protein nodes. Moreover, proteomic and in silico data were combined with immunohistochemistry and western blotting to identify a group of proteins representative of some selected pathways, with a dysregulated expression in myoma, pseudocapsule, and normal myometrium samples. Based on these results, we confirmed the over-expression of extracellular matrix components, and estrogen and progesterone receptors in uterine myomas, and proposed biological networks, canonical pathways and functions that may be relevant to the pathophysiology of this tumor. PMID- 27001060 TI - Angiogenesis and Vascularization of Uterine Leiomyoma: Clinical Value of Pseudocapsule Containing Peptides and Neurotransmitters. AB - Fibroids or myomas involve large proportion of women of reproductive age. The myoma formation starts from the transformation of the myometrium, causing the progressive formation of a pseudocapsule, which is made of compressed muscle fibers. Numerous studies investigated on myoma pseudocapsule anatomy, discovering many neurotransmitters and neuropeptides, as a neurovascular bundle, influencing myometrial physiology. These substances have a positive impact on wound healing and muscular restoring, also playing a role in sexual and reproductive function. Based on investigations, a distinct surgical technique evolved, called "intracapsular myomectomy", meaning myoma removal from its pseudocapsule, which enables protection of the myoma pseudocapsule, containing neuropeptides and neurofibers involved in physiological myometrial healing. This technique, performed by a gentle myoma enucleating by stretching from myometrium and sparing pseudocapsule, reduces surgical trauma caused by iatrogenic myoma pseudocapsule damage. Intracapsular myomectomy meets the basic surgical anatomy principle: myoma is removed by a bloodless, precise and careful dissection sparing myometrium, as much as possible. The rationale of intracapsular myomectomy should be applied to all myoma removals; therefore, it has been used for both laparoscopic and laparotomic myomectomy, as well as for cesarean myomectomy. Scientific research is still seeks to clarify some reports of myomas with infertility, especially in the case of intramural myomas, but it is clear that in the case of performing myomectomy, it must do by the described intracapsular technique. This enables myometrial preservation, especially peripherally to myoma bed, promoting myometrial healing after myoma removal. PMID- 27001061 TI - Uterine Cervical Neurotransmission and Cervical Remodeling. AB - Cervical remodeling (CR) is a complex process, which, in part, is believed to be induced by physiological inflammation. Even though the female reproductive tissues are richly innervated by nerves from the parasympathetic pelvic autonomic ganglia, sensory dorsal root and nodose ganglia, their roles (neuronal factors) in this process (CR) has been largely attributed to sex steroid hormones, until recently. Here, we discuss the interaction between neuropeptides derived from peripheral nerves associated with uterine cervix and estrogen, and their likely impact on cervical remodeling. It is likely that these neuronal factors, under the influence of estrogen, could induce physiological inflammation during cervical remodeling by promoting the expression of vascular endothelial growth factor, among other factors. PMID- 27001062 TI - Laminin and Collagen IV: Two Polypeptides as Marker of Dystocic Labor. AB - Collagen IV and Laminin are localized in cells and tissue of numerous human organs including the uterus, where these polypeptides control either age changes, or uterus growth in pregnancy, or ripening and dilatation in labor. Authors examined the polypeptides distribution of collagen IV and Laminin in the human pregnant uterus, in normal and dystocic labor, to clarify their physiologic role, by distribution and/or their changes in prolonged dystocic labor. We collected lower uterine segment (LUS) fragments during cesarean section (CS); these biopsies were treated with basic morphological staining for the observation of microscopic- anatomic details. Other samples were processed with immunohistochemical staining for collagen IV and for membrane bound Laminin. All morphological and immunochemical results were analyzed with quantitative analysis of images and statistical analysis of data. Both Collagen IV and Laminin show changes in the pregnant uterus before 4 hours of full cervical dilatation in patients after 4 hours. All the three types of the human uterine cells, mucosal, submucosal and smooth muscular cells, are more reduced in LUS after 4 hours of cervical dilatation in dystocic labor. The connective tissues (including fibroblast) show the most evident changes in the dystocic LUS, collagen IV and laminin changes during cervical dilatation in prolonged dystocic labor, with a decreased elasticity with increased roughness and dryness. The LUS anatomical modifications during labor can be the cause of pathological changes in protracted dystocic labor. In the dystocic labor that lasts more than 4 hours from the complete cervical ripening and dilatation, the laminin and collagen IV concentration reduces in the LUS tissue. In dystocic labor, delivery should be completed before the 3 hours of full dilation, to avoid a reduction of laminin and collagen IV and a worsening of LUS healing for the next pregnancy. PMID- 27001063 TI - Neurotransmitters and Neuropeptides Expression in the Uterine Scar After Cesarean Section. AB - Peptides and neuropeptides influence the uterine disorders of healing or cicatrization, chronic pelvic pain and disorder of pregnancy, labor and puerperium. They also promote changes in the lower uterine segment (LUS) during pregnancy, labor and delivery. We investigated the tissue quantity of neurotensin (NT), neuropeptide tyrosin (NPY) and Protein Gene Product 9.5 (PGP 9.5) in women submitted to elective cesarean section (CS) and urgent CS. During surgery, authors biopsied tissue samples of vesico-uterine space (VUS) to detect nerve fibers, and compared them. VUS samples from 106 patients have been evaluated with light microscopy, immunochemistry and Immunohistochemistry, and finally by Quantimet Leica analyzer software. Significantly higher amount of nerve fibers, containing NT, NPY and PGP 9.5 have been found in VUS tissue samples obtained during the first elective CS and during the first urgent CS were respectively 5+/ 0.7, 7+/-0.6 and 5+/-0.9 CU and 2.5+/-0.5, 3.6+/-0.4 and 3.5+/-0.9 CU (p<0.05). This neurotransmitter reduction should indicate the inflammatory damage of cervical tissue for LUS over distension in dystocic-prolonged labor before CS. These results may be correlated with the decrease of NT, NPY and PGP 9.5, responsible for an optimal healing and LUS functions. In our opinion, the presence of neuropeptides reduction in uterine samples of women undergoing urgent CS may be due to a prolonged fetal head station in LUS, with a tissue denervation, in consequence of both overdistension and inflammatory process of the dystocic LUS. PMID- 27001064 TI - Uterine Wound Healing: A Complex Process Mediated by Proteins and Peptides. AB - Wound healing is the process by which a complex cascade of biochemical events is responsible of the repair the damage. In vivo, studies in humans and mice suggest that healing and post-healing heterogeneous behavior of the surgically wounded myometrium is both phenotype and genotype dependent. Uterine wound healing process involves many cells: endothelial cells, neutrophils, monocytes/macrophages, lymphocytes, fibroblasts, myometrial cells as well a stem cell population found in the myometrium, myoSP (side population of myometrial cells). Transforming growth factor beta (TGF-beta) isoforms, connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNF-beta) are involved in the wound healing mechanisms. The increased TGF- beta1/beta3 ratio reduces scarring and fibrosis. The CTGF altered expression may be a factor involved in the abnormal scars formation of low uterine segment after cesarean section and of the formation of uterine dehiscence. The lack of bFGF is involved in the reduction of collagen deposition in the wound site and thicker scabs. The altered expression of TNF-beta, VEGF, and PDGF in human myometrial smooth muscle cells in case of uterine dehiscence, it is implicated in the uterine healing process. The over-and under-expressions of growth factors genes involved in uterine scarring process could represent patient's specific features, increasing the risk of cesarean scar complications. PMID- 27001065 TI - Biochemical Pathways and Myometrial Cell Differentiation Leading to Nodule Formation Containing Collagen and Fibronectin. AB - Utilizing both primary myometrial cells and a myometrial cell line, we show here that myometrial cells undergo transition to a myofibroblast-like phenotype after a biological insult of 72 hours serum starvation and serum add-back (SB: 1% to 10% FBS). We also found that thrombospondin-1 was increased and that the transforming growth factor-beta (TGFB)-SMAD3/4 pathway was activated. This pathway is a key mediator of fibrosis and extracellular matrix (ECM) deposition. Applying the same insult supplemented with TGFB3 (1-10ng/ml) and ascorbic acid (100MUg/ml) in the serum add-back treatment, we further demonstrated that cells migrated into nodules containing collagen and fibronectin. The number of cellnodules was inversely related to the percentage serum add-back. Using transmission electron microscopy we demonstrated myofibroblast-like cells and fibril-like structures in the extracellular spaces of the nodules. This study is the first direct evidence of induction of myofibroblast transdifferentiation in cultured myometrial cells which is related to the increase of thrombospondin-1 (THBS1) and the activation of TGFBSMAD 3 / 4 pathways. Combined, these observations provide biochemical and direct morphological evidence that fibrotic responses can occur in cultured myometrial cells. The findings are the first to demonstrate uterine healing mechanisms at a molecular level. Our data support the concept that fibrosis may be an initial event in formation of fibroid which exhibits signaling pathways and molecular features of fibrosis and grow by both cellular proliferation and altered extracellular matrix accumulation. Our data assists in further understanding of myometrium tissue remodeling during gestation and postpartum. PMID- 27001066 TI - Plasticity in Uterine Innervation: State of the Art. AB - Early studies often claimed that autonomic nerves were unimportant for uterine function, since denervation of the uterus had little effects on reproductive success. In 1979, Thorbert wrote, "It seems unlikely that Nature has equipped the uterus with a complex innervation merely as a structural ornament. Our ignorance in this area may be rather due to defects in methods of study". Investigations carried out over the last four decades proved that Thorbert's words were correct, because it is now clear that autonomic and sensory nerves regulate many critical uterine functions. However, the most remarkable aspect of uterine innervation is its capacity to change in response to physiological fluctuations in levels of sex hormones, as those accompanying pregnancy, the sex cycle and puberty. The present review provides an overview about how sex hormones influence uterine innervation. Data are presented about how this physiological plasticity is mimicked by exogenous administration of sex hormones, particularly estrogen. We will review recent developments illustrating the complex multifactorial mechanisms regulating uterine neural plasticity and the nature of molecular signals involved. Finally, we will go through recent findings pointing to the relevance of uterine innervation in gynecological diseases leading to pain and infertility. PMID- 27001067 TI - Junior doctors vote to escalate industrial action. PMID- 27001068 TI - BRE plays an essential role in preventing replicative and DNA damage-induced premature senescence. AB - The BRE gene, alias BRCC45, produces a 44 kDa protein that is normally distributed in both cytoplasm and nucleus. In this study, we used adult fibroblasts isolated from wild-type (WT) and BRE knockout (BRE(-/-)) mice to investigate the functional role of BRE in DNA repair and cellular senescence. We compared WT with BRE(-/-) fibroblasts at different cell passages and observed that the mutant fibroblasts entered replicative senescence earlier than the WT fibroblasts. With the use of gamma irradiation to induce DNA damage in fibroblasts, the percentage of SA-beta-Gal(+) cells was significantly higher in BRE(-/-) fibroblasts compared with WT cells, suggesting that BRE is also associated with DNA damage-induced premature senescence. We also demonstrated that the gamma irradiation induced gamma-H2AX foci, a DNA damage marker, persisted significantly longer in BRE(-/-) fibroblasts than in WT fibroblasts, confirming that the DNA repair process is impaired in the absence of BRE. In addition, the BRCA1-A complex recruitment and homologous recombination (HR) dependent DNA repair process upon DNA damage were impaired in BRE(-/-) fibroblasts. Taken together, our results demonstrate a role for BRE in both replicative senescence and DNA damage-induced premature senescence. This can be attributed to BRE being required for BRCA1-A complex-driven HR DNA repair. PMID- 27001069 TI - General odorant-binding proteins and sex pheromone guide larvae of Plutella xylostella to better food. AB - Olfaction of Lepidopteran larvae has received little attention, compared to the damage to crops done by insects at this stage. We report that larvae of the diamondback moth Plutella xylostella are attracted to their natural sex pheromone and to their major component (Z)-11-hexadecenal, but only in a food context. For such task they use two general odorant-binding proteins (GOBPs), abundantly expressed in the three major sensilla basiconica of the larval antenna, as shown by whole-mount immunostaining and immunocytochemistry experiments. None of the three genes encoding pheromone-binding proteins (PBPs) are expressed at this stage. Both recombinant GOBPs bind (Z)-11-hexadecenal and the corresponding alcohol, but not the acetate. Binding experiments performed with five mutants of GOBP2, where aromatic residues in the binding pocket were replaced with leucine showed that only one or two amino acid substitutions can completely abolish binding to the pheromone shifting the affinity to plant-derived compounds. We hypothesise that detection of their species-specific pheromone may direct larvae to the sites of foraging chosen by their mother when laying eggs, to find better food, as well as to reduce competition with individuals of the same or other species sharing the same host plant. We also provide evidence that GOBP2 is a narrowly tuned binding protein, whose affinity can be easily switched from linear pheromones to branched plants terpenoids, representing a tool better suited for the simple olfactory system of larvae, as compared to the more sophisticated organ of adults. PMID- 27001070 TI - The ACBP gene family in Rhodnius prolixus: Expression, characterization and function of RpACBP-1. AB - The acyl-CoA-binding proteins (ACBP) constitute a family of conserved proteins that bind acyl-CoA with high affinity and protect it from hydrolysis. Thus, ACBPs may have essential roles in basal cellular lipid metabolism. The genome of the insect Rhodnius prolixus encodes five ACBP genes similar to those described for other insect species. The qPCR analysis revealed that these genes have characteristic expression profiles in insect organs, suggesting that they have specific roles in insect physiology. Recombinant RpACBP-1 was able to bind acyl CoA in an in vitro gel-shift assay. Moreover, heterologous RpACBP-1 expression in acb1Delta mutant yeast rescued the multi-lobed vacuole phenotype, indicating that RpACBP-1 acts as a bona fide acyl-CoA-binding protein. RpACBP-1 knockdown using RNAi caused triacylglycerol accumulation in the insect posterior midgut and a reduction in the number of deposited eggs. The amount of stored triacylglycerol was reduced in flight muscle, and the incorporation of fatty acids in cholesteryl esters was increased in the fat body. These results showed that RpACBP-1 participates in several lipid metabolism steps in R. prolixus. PMID- 27001071 TI - Knockdown of Drosophila hemoglobin suggests a role in O2 homeostasis. AB - Almost all insects are equipped with a tracheal system, which appears to be sufficient for O2 supply even in phases of high metabolic activity. Therefore, with the exception of a few species dwelling in hypoxic habitats, specialized respiratory proteins had been considered unnecessary in insects. The recent discovery and apparently universal presence of intracellular hemoglobins in insects has remained functionally unexplained. The fruitfly Drosophila melanogaster harbors three different globin genes (referred to as glob1-3). Glob1 is the most highly expressed globin and essentially occurs in the tracheal system and the fat body. To better understand the functions of insect globins, the levels of glob1 were modulated in Drosophila larvae and adults by RNAi-mediated knockdown and transgenic over-expression. No effects on the development were observed in flies with manipulated glob1 levels. However, the knockdown of glob1 led to a significantly reduced survival rate of adult flies under hypoxia (5% and 1.5% O2). Surprisingly, the glob1 knockdown flies also displayed increased resistance towards the reactive oxygen species-forming agent paraquat, which may be explained by a restricted availability of O2 resulting in decreased formation of harmful O2(-). In summary, our results suggest an important functional role of glob1 in O2 homeostasis, possibly by enhancing O2 supply. PMID- 27001072 TI - Preparation of Reactive Oligo(p-Phenylene Vinylene) Materials for Spatial Profiling of the Chemical Reactivity of Intracellular Compartments. AB - An oligo(p-phenylene vinylene) derivative (OPV-pfp) functionalized with pentafluorophenol active ester is designed and synthesized. The high reactivity of OPV-pfp with biological small molecules or macromolecules containing amino groups under physiological conditions leads to spectral changes of OPV-pfp; thus, spatial reactivity discrimination for different subcellular structures inside cells is realized by triggering and imaging the fluorescence signal change of the OPV-pfp. PMID- 27001074 TI - Antimicrobial activity of mul-1867, a novel antimicrobial compound, against multidrug-resistant Pseudomonas aeruginosa. AB - BACKGROUND: There is an urgent need for new antimicrobial compounds to treat various lung infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR PA). METHODS: We studied the potency of Mul-1867 against MDR-PA isolates from patients with cystic fibrosis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia. The minimal inhibitory concentrations (MICs) and minimum biofilm eliminating concentrations (MBECs), defined as the concentrations of drug that kill 50 % (MBEC50), 90 % (MBEC90), and 100 % (MBEC100) of the bacteria in preformed biofilms, were determined by using the broth macrodilution method. RESULTS: Mul-1867 exhibited significant activity against MDR-PA and susceptible control strains, with MICs ranging from 1.0 to 8.0 ug/mL. Mul-1867 also possesses anti-biofilm activity against mucoid and non-mucoid 24-h-old MDR PA biofilms. The MBEC50 value was equal to onefold the MIC. The MBEC90 value ranged from two to fourfold the MIC. Moreover, Mul-1867 completely eradicated mature biofilms at the concentrations tested, with MBEC100 values ranging between 16- and 32-fold the MIC. Mul-1867 was non-toxic to Madin-Darby canine kidney (MDCK) cells at concentrations up to 256 ug/mL. CONCLUSION: Overall, these data indicate that Mul-1867 is a promising locally acting antimicrobial for the treatment and prevention of P. aeruginosa infections. PMID- 27001073 TI - Prognostic factors and risk stratification in patients with castration-resistant prostate cancer receiving docetaxel-based chemotherapy. AB - BACKGROUND: While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy. METHODS: This study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis. RESULTS: PSA response >=50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS. CONCLUSIONS: Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival. PMID- 27001076 TI - Addressing non-communicable diseases in disaster risk reduction - an issue of equity. AB - The issues raised by noncommunicable diseases (NCDs) during and after disasters are a challenge to equity within local communities, as well as between countries. Individuals with NCDs are particularly vulnerable in disasters and their aftermath given health systems are disrupted. Although welcome progress has been made in taking NCDs and equity into account in the UN General Assembly ratified agreement, the Sendai Framework for disaster risk reduction 2015-2030, there is need now for a clear plan of implementation. PMID- 27001075 TI - A simple method for studying the molecular mechanisms of ultraviolet and violet reception in vertebrates. AB - BACKGROUND: Many vertebrate species use ultraviolet (UV) reception for such basic behaviors as foraging and mating, but many others switched to violet reception and improved their visual resolution. The respective phenotypes are regulated by the short wavelength-sensitive (SWS1) pigments that absorb light maximally (lambdamax) at ~360 and 395-440 nm. Because of strong epistatic interactions, the biological significance of the extensive mutagenesis results on the molecular basis of spectral tuning in SWS1 pigments and the mechanisms of their phenotypic adaptations remains uncertain. RESULTS: The magnitudes of the lambdamax-shifts caused by mutations in a present-day SWS1 pigment and by the corresponding forward mutations in its ancestral pigment are often dramatically different. To resolve these mutagenesis results, the A/B ratio, in which A and B are the areas formed by amino acids at sites 90, 113 and 118 and by those at sites 86, 90 and 118 and 295, respectively, becomes indispensable. Then, all critical mutations that generated the lambdamax of a SWS1 pigment can be identified by establishing that 1) the difference between the lambdamax of the ancestral pigment with these mutations and that of the present-day pigment is small (3 ~ 5 nm, depending on the entire lambdamax-shift) and 2) the difference between the corresponding A/B ratios is < 0.002. CONCLUSION: Molecular adaptation has been studied mostly by using comparative sequence analyses. These statistical results provide biological hypotheses and need to be tested using experimental means. This is an opportune time to explore the currently available and new genetic systems and test these statistical hypotheses. Evaluating the lambdamaxs and A/B ratios of mutagenized present-day and their ancestral pigments, we now have a method to identify all critical mutations that are responsible for phenotypic adaptation of SWS1 pigments. The result also explains spectral tuning of the same pigments, a central unanswered question in phototransduction. PMID- 27001077 TI - How Does Scale of Implementation Impact the Environmental Sustainability of Wastewater Treatment Integrated with Resource Recovery? AB - Energy and resource consumptions required to treat and transport wastewater have led to efforts to improve the environmental sustainability of wastewater treatment plants (WWTPs). Resource recovery can reduce the environmental impact of these systems; however, limited research has considered how the scale of implementation impacts the sustainability of WWTPs integrated with resource recovery. Accordingly, this research uses life cycle assessment (LCA) to evaluate how the scale of implementation impacts the environmental sustainability of wastewater treatment integrated with water reuse, energy recovery, and nutrient recycling. Three systems were selected: a septic tank with aerobic treatment at the household scale, an advanced water reclamation facility at the community scale, and an advanced water reclamation facility at the city scale. Three sustainability indicators were considered: embodied energy, carbon footprint, and eutrophication potential. This study determined that as with economies of scale, there are benefits to centralization of WWTPs with resource recovery in terms of embodied energy and carbon footprint; however, the community scale was shown to have the lowest eutrophication potential. Additionally, technology selection, nutrient control practices, system layout, and topographical conditions may have a larger impact on environmental sustainability than the implementation scale in some cases. PMID- 27001078 TI - Gene therapy grows up (and moves out of the house). PMID- 27001079 TI - Patient safety work in Sweden: quantitative and qualitative analysis of annual patient safety reports. AB - BACKGROUND: There is widespread recognition of the problem of unsafe care and extensive efforts have been made over the last 15 years to improve patient safety. In Sweden, a new patient safety law obliges the 21 county councils to assemble a yearly patient safety report (PSR). The aim of this study was to describe the patient safety work carried out in Sweden by analysing the PSRs with regard to the structure, process and result elements reported, and to investigate the perceived usefulness of the PSRs as a tool to achieve improved patient safety. METHODS: The study was based on two sources of data: patient safety reports obtained from county councils in Sweden published in 2014 and a survey of health care practitioners with strategic positions in patient safety work, acting as key informants for their county councils. Answers to open-ended questions were analysed using conventional content analysis. RESULTS: A total of 14 structure elements, 31 process elements and 23 outcome elements were identified. The most frequently reported structure elements were groups devoted to working with antibiotics issues and electronic incident reporting systems. The PSRs were perceived to provide a structure for patient safety work, enhance the focus on patient safety and contribute to learning about patient safety. CONCLUSION: Patient safety work carried out in Sweden, as described in annual PSRs, features a wide range of structure, process and result elements. According to health care practitioners with strategic positions in the county councils' patient safety work, the PSRs are perceived as useful at various system levels. PMID- 27001080 TI - Management of three cardiogenic pulmonary edemas occurring in a patient scheduled for left ventricular assist device implantation: indicators for determining left ventricular assist device pump speed. AB - A male patient with Marfan syndrome underwent aortic root replacement and developed left ventricular (LV) failure. Four years later, he underwent aortic arch and aortic valve replacement. Thereafter, his LV failure progressed, and cardiogenic pulmonary edema (CPE) appeared, which we treated with extracorporeal LV assist device (LVAD) placement. Three months later, the patient developed aspiration pneumonia, which caused hyperdynamic right ventricle (RV) and CPE. We treated by changing his pneumatic LVAD to a high-flow centrifugal pump. A month later, he underwent thoracoabdominal aortic replacement. After four weeks, he developed septic thrombosis and LVAD failure, which caused CPE. We treated with LVAD circuit replacement and an additional membrane oxygenator. Four months later, he underwent DuraHeart((r)) implantation. During this course, pulmonary artery wedge pressure (PAWP) varied markedly. Additionally, systolic pulmonary artery pressure (sPAP), left atrial diameter (LAD), RV end-diastolic diameter (RVEDD) and estimated RV systolic pressure (esRVP) changed with PAWP changes. In this patient, LV failure and hyperdynamic RV caused the CPEs, which we treated by adjusting the LVAD output to the RV output. Determining LVAD output, RV function and LV end-diastolic diameter are typically referred, and PAWP, LAD, RVEDD, and sPAP could be also referred. PMID- 27001082 TI - Inattentional blindness: A combination of a relational set and a feature inhibition set? AB - Two experiments were conducted to directly test the feature set hypothesis and the relational set hypothesis in an inattentional blindness task. The feature set hypothesis predicts that unexpected objects that match the to-be-attended stimuli will be reported most. The relational set hypothesis predicts that unexpected objects that match the relationship between the to-be-attended and the to-be ignored stimuli will be reported the most. Experiment 1 manipulated the luminance of the stimuli. Participants were instructed to monitor the gray letter shapes and to ignore either black or white letter shapes. The unexpected objects that exhibited the luminance relation of the to-be-attended to the to-be-ignored stimuli were reported by participants the most. Experiment 2 manipulated the color of the stimuli. Participants were instructed to monitor the yellower orange or the redder orange letter shapes and to ignore the redder orange or yellower letter shapes. The unexpected objects that exhibited the color relation of the to be-attended to the to-be-ignored stimuli were reported the most. The results do not support the use of a feature set to accomplish the task and instead support the use of a relational set. In addition, the results point to the concurrent use of multiple attentional sets that are both excitatory and inhibitory. PMID- 27001081 TI - Hyperoxic oxidative stress during abdominal surgery: a randomized trial. AB - PURPOSE: The hypothesis of our study is that during anesthesia, administration of 80 % oxygen concentration increases oxidative stress more than 40 % oxygen. METHODS: Forty ASA I-II patients were included in a randomized, single-blind study. Expiratory tidal volumes (ETV) were measured before induction and after extubation. After ventilation with 0.8 FiO2 and intubation, mini-bronchoalveolar lavage (mini-BAL), arterial blood gas (ABG), and blood samples were taken. Patients were randomly assigned to receive 0.8 (group I) or 0.4 (group II) FiO2 during management. Before extubation, mini-BAL, ABG, blood samples were taken. PaO2/FiO2, lactate, malondialdehyde (MDA), protein carbonyl (PCO), superoxide dismutase (SOD), total sulfhydryl (T-SH), non-protein sulfhydryl (NPSH), and protein sulfhydryl (PSH) were measured. In both groups, mean arterial pressure and heart rate values were recorded with 30-min intervals. RESULTS: ETV values were higher in group II after extubation. PaO2/FiO2 values were higher in group II after extubation compared to group I. In both groups, plasma PCO, SOD, and T SH levels increased significantly before extubation, whereas the increase in MDA was not significant between groups. Plasma PCO, T-SH, and lactate levels were higher in group I, and plasma SOD, and PSH were higher in group I before extubation. In both groups, MDA, SOD, T-SH, and NPSH levels in mini-BAL increased significantly before extubation. Between-group comparisons, PCO, T-SH, PSH, and NPSH were significantly higher in the BAL samples of group II, and MDA levels were higher in group I. CONCLUSIONS: We found that 80 % FiO2 decreased ETV and PaO2/FiO2 and increased lactate levels and oxidative stress more, inhibiting antioxidant response compared to 40 % FiO2. PMID- 27001083 TI - Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations, including a known exon 19 deletion (19 del) and exon 21 L858R point mutation (L858R mutation), are strong predictors of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment in lung adenocarcinoma. However, whether patients carrying EGFR 19 del and L858R mutations exhibit different responsiveness to EGFR-TKIs and what are the potential mechanism for this difference remain controversial. This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes. METHODS: Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858R mutations, 532 received EGFR-TKI treatment and were included in this study. EGFR 19 del and L858R mutations were detected by using denaturing high-performance liquid chromatography (DHPLC). T790M mutation, which is a common resistant mutation on exon 20 of EGFR, was detected by amplification refractory mutation system (ARMS). Next-generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations. RESULTS: Of the 532 patients, 319 (60.0%) had EGFR 19 del, and 213 (40.0%) had L858R mutations. The patients with EGFR 19 del presented a significantly higher overall response rate (ORR) for EGFR-TKI treatment (55.2% vs. 43.7%, P = 0.017) and had a longer progression-free survival (PFS) after first-line EGFR-TKI treatment (14.4 vs. 11.4 months, P = 0.034) compared with those with L858R mutations. However, no statistically significant difference in overall survival (OS) was observed between the two groups of patients. T790M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment, and there was no significant difference in the co-existence of T790M mutation with EGFR 19 del and L858R mutations before EGFR-TKI treatment (5.6% vs. 8.8%, P = 0.554) or after treatment (24.4% vs. 35.4%, P = 0.176). In addition, 24 patients with EGFR 19 del and 19 with L858R mutations were analyzed by NGS, and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes. CONCLUSIONS: Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858R mutations. Whether the heterogeneity of tumors with EGFR 19 del and L858R mutations contribute to a therapeutic response difference needs further investigation. PMID- 27001084 TI - Seasonal cues induce phenotypic plasticity of Drosophila suzukii to enhance winter survival. AB - BACKGROUND: As global climate change and exponential human population growth intensifies pressure on agricultural systems, the need to effectively manage invasive insect pests is becoming increasingly important to global food security. Drosophila suzukii is an invasive pest that drastically expanded its global range in a very short time since 2008, spreading to most areas in North America and many countries in Europe and South America. Preliminary ecological modeling predicted a more restricted distribution and, for this reason, the invasion of D. suzukii to northern temperate regions is especially unexpected. Investigating D. suzukii phenology and seasonal adaptations can lead to a better understanding of the mechanisms through which insects express phenotypic plasticity, which likely enables invasive species to successfully colonize a wide range of environments. RESULTS: We describe seasonal phenotypic plasticity in field populations of D. suzukii. Specifically, we observed a trend of higher proportions of flies with the winter morph phenotype, characterized by darker pigmentation and longer wing length, as summer progresses to winter. A laboratory-simulated winter photoperiod and temperature (12:12 L:D and 10 degrees C) were sufficient to induce the winter morph phenotype in D. suzukii. This winter morph is associated with increased survival at 1 degrees C when compared to the summer morph, thus explaining the ability of D. suzukii to survive cold winters. We then used RNA sequencing to identify gene expression differences underlying seasonal differences in D. suzukii physiology. Winter morph gene expression is consistent with known mechanisms of cold-hardening such as adjustments to ion transport and up-regulation of carbohydrate metabolism. In addition, transcripts involved in oogenesis and DNA replication were down-regulated in the winter morph, providing the first molecular evidence of a reproductive diapause in D. suzukii. CONCLUSIONS: To date, D. suzukii cold resistance studies suggest that this species cannot overwinter in northern locations, e.g. Canada, even though they are established pests in these regions. Combining physiological investigations with RNA sequencing, we present potential mechanisms by which D. suzukii can overwinter in these regions. This work may contribute to more accurate population models that incorporate seasonal variation in physiological parameters, leading to development of better management strategies. PMID- 27001085 TI - Childhood overweight in Berlin: intra-urban differences and underlying influencing factors. AB - BACKGROUND: In recent years, childhood overweight and obesity have become an increasing and challenging phenomenon in Western cities. A lot of studies have focused on the analysis of factors such as individual dispositions and nutrition balances, among others. However, little is known about the intra-urban spatial patterns of childhood overweight and its associations with influencing factors that stretch from an individual to a neighbourhood level. The aim of this paper is to analyse the spatial patterns of childhood obesity in Berlin, and also to explore and test for associations with a complex set of risk factors at the individual, household and neighbourhood levels. METHODS: We use data from a survey of 5-6 year-olds that includes health status, height, and weight, as well as several socioeconomic and other risk variables. In addition, we use a set of neighbourhood variables, such as distance, and density measures of parks or fast food restaurants. Our outcome variable is the percentage of children of 5-6 years who were reported overweight or obese in 2012. The aggregated data is available for 60 areas in Berlin. We first analyse the outcome and risk factor data descriptively, and subsequently apply a set of regression analyses to test for associations between reported overweight and obesity, and also individual, household and neighbourhood characteristics. RESULTS: Our analysis returned a distinct spatial distribution of childhood overweight in Berlin with highest shares in the city centre. Moreover, we were able to identify significant effects regarding the social index, and the percentage of non-German children being obese or overweight; additionally, we identified fast food restaurant density as a possible influencing factor. For the other variables, including the neighbourhood variables, we could not identify a significant association on this aggregated level of analysis. CONCLUSIONS: Our findings confirm the results of earlier studies, in which the social status and percentage of non-German children is very important in terms of the association with childhood overweight and obesity. Unlike many studies conducted in North America, this study did not reveal an influence of neighbourhood variables. We argue that European urban structures differ from North American structures and highlight the need for a more detailed analysis of the association between the neighbourhood environment and the physical activity of children in urban setting. PMID- 27001086 TI - Update: New England Journal of Medicine publishes correction to 2012 CHEST trial of hydroxyethyl starch versus colloids. PMID- 27001087 TI - The role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes: A preliminary report. AB - Recent studies suggest that immune activation and cytokines, such as IL-18, are involved in depression. IL-18 is expressed in brain and is increased in patients with moderate to severe depression. In this study we aim to evaluate the role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes, specifically relapse and treatment resistant depression (TRD). We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhaes Lemos, Portugal, within a period of 27 months. Patients carrying IL18-607 CA or AA genotypes were significantly more prone to relapse after AD treatment and present a significantly lower time to relapse than patients carrying CC genotype. Similarly, patients carrying IL18-137 GC or CC genotypes have a significantly higher risk of relapse and display relapse significantly earlier than the ones carrying GG genotype. Due to the low number of IL18-607 CC and IL18-137 GG in the relapse subgroup (n=3 and n=5, respectively), results were validated by bootstrapping analysis, and remained significant. No association was found between the evaluated genetic polymorphisms and TRD. IL18 peripheral mRNA levels were upregulated in IL18-607 CA or AA carriers. This preliminary report indicates that IL18-607C>A and IL18-137G>C genetic polymorphisms seem to influence depression relapse after antidepressant treatment in our subset of depressed patients, and may possibly contribute to the disregulated IL-18 levels found in patients with depression. PMID- 27001088 TI - Exonic rearrangements in the known Parkinson's disease-causing genes are a rare cause of the disease in South African patients. AB - Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. To date, a number of PD-causing genes have been found, including SNCA, LRRK2, VPS35, PARK2, PINK1, DJ-1, ATP13A2, and most recently CHCHD2. Mutations in these genes range from point mutations to larger exonic rearrangements including deletions and duplications. This study aimed to detect possible copy number variation (CNV) in the known PD-causing genes in a cohort of South African patients with PD. Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed on a total of 210 South African PD patients, and possible CNVs were verified using quantitative real time PCR. No homozygous or compound heterozygous exon rearrangements in the genes analysed were found in the patient group. A heterozygous PARK2 exon 4 deletion was found in a sporadic patient with an age at onset of 51 years. Sanger sequencing did not reveal any additional mutations in PARK2 in this patient. Combining our results with that of previous studies in a South African cohort, the frequency of exonic rearrangements in the known PD causing genes is only 1.8% (8/439 patients). In conclusion, CNV in the known PD causing genes are a rare cause of PD in a South African cohort, and there may be as yet unknown genetic causes of PD that are specific to patients of African ethnicity. PMID- 27001089 TI - Innovations to more effectively engage patients and caregivers across the health care spectrum. PMID- 27001090 TI - Crowdsourcing healthcare costs: Opportunities and challenges for patient centered price transparency. AB - Efforts to improve health care price transparency have garnered significant attention from patients, policy makers, and health insurers. In response to increasing consumer demand, state governments, insurance plans, and health care providers are reporting health care prices. However, such data often do not provide consumers with the most salient information: their own actual out-of pocket cost for medical care. Although untested, crowdsourcing, a mechanism for the public to help answer complex questions, represents a potential solution to the problem of opaque hospital costs. This article explores, the challenges and potential opportunities for crowdsourcing out-of-pocket costs for healthcare consumers. PMID- 27001091 TI - Does assessment of patient satisfaction with pain care lead to patient harm? PMID- 27001092 TI - The role of peer support specialists for patients with medical and behavioral health needs--Challenges and opportunities. PMID- 27001093 TI - A design thinking framework for healthcare management and innovation. AB - The business community has learned the value of design thinking as a way to innovate in addressing people's needs--and health systems could benefit enormously from doing the same. This paper lays out how design thinking applies to healthcare challenges and how systems might utilize this proven and accessible problem-solving process. We show how design thinking can foster new approaches to complex and persistent healthcare problems through human-centered research, collective and diverse teamwork and rapid prototyping. We introduce the core elements of design thinking for a healthcare audience and show how it can supplement current healthcare management, innovation and practice. PMID- 27001094 TI - How U.S. children's hospitals use social media: A mixed methods study. AB - BACKGROUND: Social media provide new channels for hospitals to engage with communities, a goal of increasing importance as non-profit hospitals face stricter definitions of community benefit under the Affordable Care Act. We describe the variability in social media presence among US children's hospitals and the distribution of their Facebook content curation. METHODS: Social media data from freestanding children's hospitals were extracted from September November 2013. Social media adoption was reviewed for each hospital-generated Facebook, Twitter, YouTube, Google+ and Pinterest platform. Facebook page (number of Likes) and Twitter account (number of followers) engagement were examined by hospital characteristics. Facebook posts from each hospital over a 6-week period were thematically characterized. RESULTS: We reviewed 5 social media platforms attributed to 45 children's hospitals and 2004 associated Facebook posts. All hospitals maintained Facebook and Twitter accounts and most used YouTube (82%), Google+ (53%) and Pinterest (69%). Larger hospitals were more often high performers for Facebook (67% versus 10%, p<0.01) and Twitter (75% versus 17%, p<0.05) engagement than small hospitals. The most common Facebook post-themes were hospital promotion 35% (706), education and information 35% (694), community partnership or benefit 24% (474), fundraising 21% (426), and narratives 12% (241). Of health education posts, 73% (509) provided pediatric health supervision and anticipatory guidance. CONCLUSIONS: Social media adoption by US children's hospitals was widespread. IMPLICATIONS: Beyond its traditional marketing role, social media can serve as a conduit for health education, engagement with communities, including community benefit. PMID- 27001095 TI - Key ingredients for implementing intensive outpatient programs within patient centered medical homes: A literature review and qualitative analysis. AB - BACKGROUND: Intensive outpatient programs aim to transform care while conserving resources for high-need, high-cost patients, but little is known about factors that influence their implementation within patient-centered medical homes (PCMHs). METHODS: In this mixed-methods study, we reviewed the literature to identify factors affecting intensive outpatient program implementation, then used semi-structured interviews to determine how these factors influenced the implementation of an intensive outpatient program within the Veterans Affairs' (VA) PCMH. Interviewees included facility leadership and clinical staff who were involved in a pilot Intensive Management Patient Aligned Care Team (ImPACT) intervention for high-need, high-cost VA PCMH patents. We classified implementation factors in the literature review and qualitative analysis using the Consolidated Framework for Implementation Research (CFIR). RESULTS: The literature review (n=9 studies) and analyses of interviews (n=15) revealed key implementation factors in three CFIR domains. First, the Inner Setting (i.e., the organizational and PCMH environment), mostly enabled implementation through a culture of innovation, good networks and communication, and positive tension for change. Second, Characteristics of Individuals, including creativity, flexibility, and interpersonal skills, allowed program staff to augment existing PCMH services. Finally, certain Intervention Characteristics (e.g., adaptability) enabled implementation, while others (e.g., complexity) generated implementation barriers. CONCLUSIONS: Resources and structural features common to PCMHs can facilitate implementation of intensive outpatient programs, but program success is also dependent on staff creativity and flexibility, and intervention adaptations to meet patient and organizational needs. IMPLICATIONS: Established PCMHs likely provide resources and environments that permit accelerated implementation of intensive outpatient programs. LEVEL OF EVIDENCE: V. PMID- 27001096 TI - Short-term and long-term effectiveness of a post-hospital care transitions program in an older, medically complex population. AB - BACKGROUND: Care transition programs can potentially reduce 30 day readmission; however, the effect on long-term hospital readmissions is still unclear. OBJECTIVE: We compared short-term (30 day) and long-term (180 day) utilization of participants enrolled in care transitions versus those matched referents eligible but not enrolled. DESIGN: This cohort study was conducted from January 1, 2011 until June 30, 2013 within a primary care academic practice. PARTICIPANTS: Patients at high risk for hospital readmission based on age and comorbid health conditions had participated in care transitions group (cases) or usual care (referent). MAIN MEASURES: The primary outcomes were 30, 90, and 180 day hospital readmissions.. Secondary outcomes included: mortality; emergency room visits and days; combined rehospitalizations and emergency room visits; and total intensive care unit days. Cox proportional hazard models using propensity score matching were used to assess rehospitalization, emergency room visits and mortality. Poisson regression models were used to compare the numbers of hospital days. KEY RESULTS: Compared to referent (n=365), Mayo Clinic Care Transitions patients exhibited a lower 30 day rehospitalization rate compared to referent; 12.4% (95% CI 8.9-15.7) versus 20.1% (95% CI 15.8-24.1%), respectively (P=0.002). At 180 days, there was no difference in rehospitalization between transitions and referent; 39.9% (95% CI 34.6-44.9%) versus 44.8% (95% CI 39.4-49.8%), (P=0.07). CONCLUSION: We observed a reduction in 30 day rehospitalization rates among those enrolled in care transitions compared to referent. However, this effect was not sustained at 180 days. More work is needed to identify how the intervention can be sustained beyond 30 days. PMID- 27001097 TI - Achieving care integration from the patients' perspective: Results from a care management program. PMID- 27001098 TI - Standard work for room entry: Linking lean, hand hygiene, and patient centeredness. AB - BACKGROUND: Healthcare-associated infections are costly and fatal. Substantial front-line, administrative, regulatory, and research efforts have focused on improving hand hygiene. PROBLEM: While broad agreement exists that hand hygiene is the most important single approach to infection prevention, compliance with hand hygiene is typically only about 40%(1). GOALS: Our aim was to develop a standard process for room entry in the intensive care unit that improved compliance with hand hygiene and allowed for maximum efficiency. STRATEGY: We recognized that hand hygiene is a single step in a substantially more complicated process of room entry. We applied Lean engineering techniques to develop a standard process that included both physical steps and also standard communication elements from provider to patients and families and created a physical environment to support this. RESULTS: We observed meaningful improvement in the performance of the new standard as well as time savings for clinical providers with each room entry. We also observed an increase in room entries that included verbal communication and an explanation of what the clinician was entering the room to do. IMPLICATIONS: The design and implementation of a standardized room entry process and the creation of an environment that supports that new process has resulted in measurable positive outcomes on the medical intensive care unit, including quality, patient experience, efficiency, and staff satisfaction. Designing a process, rather than viewing tasks that need to happen in close proximity in time (either serially or in parallel) as unrelated, simplifies work for staff and results in higher compliance to individual tasks. PMID- 27001099 TI - Team-based care to improve control of hypertension in an inner city practice. AB - The purpose of this case study was to identify which intervention or interventions, if any, resulted in improved hypertension control in an intercity public practice. Data includes interventions, graphed chronologically and the results in the form of percentage of patients with controlled hypertension. Challenges to success included understaffing of the practice and significantly limited access to appointments. Also, the variety of patients' languages and cultures presented a challenge. We reached our target of 60% of patients meeting criteria for control of hypertension. Although we instituted several interventions and all cumulatively contributed to the outcome, the two likely to be most effective were the establishment of hypertension-only appointments with either primary providers or with nurses. Both of these interventions resulted in an increased number of available appointments and improved access to timely follow up. PMID- 27001101 TI - Effectively implementing FDA medication alerts utilizing patient centered medical home clinical pharmacists. AB - FDA medication alerts can be successfully implemented within patient centered medical home (PCMH) clinics utilizing clinical pharmacists. Targeted selection of high-risk patients from an electronic database allows PCMH pharmacists to prioritize assessments. Trusting relationships between PCMH clinical pharmacists and primary care providers facilitates high response rates to pharmacist recommendations. This health system approach led by PCMH pharmacists provides a framework for proactive responses to FDA safety alerts and medication related quality measure improvement. PMID- 27001102 TI - Interview with Neel Shah, MD, MPP. PMID- 27001103 TI - Single and multi-gene phylogeny of Hepatospora (Microsporidia) - a generalist pathogen of farmed and wild crustacean hosts. AB - Almost half of all known microsporidian taxa infect aquatic animals. Of these, many cause disease in arthropods. Hepatospora, a recently erected genus, infects epithelial cells of the hepatopancreas of wild and farmed decapod crustaceans. We isolated Hepatospora spp. from three different crustacean hosts, inhabiting different habitats and niches; marine edible crab (Cancer pagurus), estuarine and freshwater Chinese mitten crab (Eriocheir sinensis) and the marine mussel symbiont pea crab (Pinnotheres pisum). Isolates were initially compared using histology and electron microscopy revealing variation in size, polar filament arrangement and nuclear development. However, sequence analysis of the partial SSU rDNA gene could not distinguish between the isolates (~99% similarity). In an attempt to resolve the relationship between Hepatospora isolated from E. sinensis and C. pagurus, six additional gene sequences were mined from on-going unpublished genome projects (RNA polymerase, arginyl tRNA synthetase, prolyl tRNA synthetase, chitin synthase, beta tubulin and heat shock protein 70). Primers were designed based on the above gene sequences to analyse Hepatospora isolated from pea crab. Despite application of gene sequences to concatenated phylogenies, we were unable to discriminate Hepatospora isolates obtained from these hosts and concluded that they likely represent a single species or, at least subspecies thereof. In this instance, concatenated phylogenetic analysis supported the SSU based phylogeny, and further, demonstrated that microsporidian taxonomies based upon morphology alone are unreliable, even at the level of the species. Our data, together with description of H. eriocheir in Asian crab farms, reveal a preponderance for microvariants of this parasite to infect the gut of a wide array of decapods crustacean hosts and the potential for Hepatospora to exist as a cline across wide geographies and habitats. PMID- 27001100 TI - Better health, less spending: Redesigning the transition from pediatric to adult healthcare for youth with chronic illness. AB - Adolescents and young adults (AYA) with serious chronic illnesses face costly and dangerous gaps in care as they transition from pediatric to adult health systems. New, financially sustainable approaches to transition are needed to close these gaps. We designed a new transition model for adolescents and young adults with a variety of serious chronic conditions. Our explicit goal was to build a model that would improve the value of care for youth 15-25 years of age undergoing this transition. The design process incorporated a review, analysis, and synthesis of relevant clinical and health services research; stakeholder interviews; and observations of high-performing healthcare systems. We identified three major categories of solutions for a safer and lower cost transition to adult care: (1) building and supporting self-management during the critical transition; (2) engaging receiving care; and (3) providing checklist-driven guide services during the transition. We propose that implementation of a program with these interventions would have a positive impact on all three domains of the triple aim - improving health, improving the experience of care, and reducing per capita healthcare cost. The transition model provides a general framework as well as suggestions for specific interventions. Pilot tests to assess the model's ease of implementation, clinical effects, and financial impact are currently underway. PMID- 27001104 TI - Simultaneous esophagectomy and off-pump coronary artery bypass grafting: a practicable approach with good survival. AB - Surgery continues to be the mainstay of esophageal cancer treatment. However, it is a big challenge for the surgical treatment of patients with both esophageal cancer and coronary artery disease (CAD). We reported, here, the first case series of esophageal cancer patients treated with simultaneous esophagectomy and off-pump coronary artery bypass grafting (CABG). From August 2010 to August 2012, 2154 esophageal or esophageal gastric junction (EGJ) cancer patients underwent surgical treatment in Tangdu Hospital, Xi'an, China. Among them, six patients with esophageal or EGJ esophageal gastric junction cancer complicated with CAD were given simultaneous esophagectomy and off-pump CABG, and were followed up until August 2014. Four patients were operated through left lateral thoracotomy and two patients were operated through median sternotomy plus upper midline laparotomy. All the patients survived the operation well and the postoperative morbidity rate was 67% (one anastomosis leakage, three cardiac arrhythmias). There was no postoperative mortality. The mean follow-up time was 34.5 +/- 7.8 months (range, 24-46 months). One patient died 36 months later due to tumor recurrence and all the other patients survived until the time to follow up. Simultaneous esophagectomy and off-pump CABG approach might be a safe and effective procedure with good survival in selected patients with both esophageal cancer and CAD. PMID- 27001105 TI - Policy implications of marked reversals of population life expectancy caused by substance use. AB - BACKGROUND: Life expectancy has been increasing steadily over the past century in most countries, with only a few exceptions such as during wartimes. DISCUSSION: Marked reversal of life expectancy has been linked to substance use and related policies. Three such examples are discussed herein, namely the double reversal of life expectancy trends (first to positive, then to negative) associated with reducing alcohol supply in the then Union of Soviet Socialist Republics (USSR), followed by a rapid increase in availability; the impact of the rapid increase of prescription opioids on white non-Hispanics in the US; and the systemic impact of the violence accompanying the drug war in Mexico on the life expectancy of men. Alcohol policies were crucial to initiate the positive reversal in the USSR, and different substance use policies could have avoided the negative impacts on life expectancy of the described large groups or nations. Substance use policies can be responsible for abrupt negative changes in life expectancies. An orientation of such policies towards the goals of public health and societal well-being can help avoid such changes. PMID- 27001106 TI - Identification and functional analyses of sex determination genes in the sexually dimorphic stag beetle Cyclommatus metallifer. AB - BACKGROUND: Genes in the sex determination pathway are important regulators of sexually dimorphic animal traits, including the elaborate and exaggerated male ornaments and weapons of sexual selection. In this study, we identified and functionally analyzed members of the sex determination gene family in the golden metallic stag beetle Cyclommatus metallifer, which exhibits extreme differences in mandible size between males and females. RESULTS: We constructed a C. metallifer transcriptomic database from larval and prepupal developmental stages and tissues of both males and females. Using Roche 454 pyrosequencing, we generated a de novo assembled database from a total of 1,223,516 raw reads, which resulted in 14,565 isotigs (putative transcript isoforms) contained in 10,794 isogroups (putative identified genes). We queried this database for C. metallifer conserved sex determination genes and identified 14 candidate sex determination pathway genes. We then characterized the roles of several of these genes in development of extreme sexual dimorphic traits in this species. We performed molecular expression analyses with RT-PCR and functional analyses using RNAi on three C. metallifer candidate genes--Sex-lethal (CmSxl), transformer-2 (Cmtra2), and intersex (Cmix). No differences in expression pattern were found between the sexes for any of these three genes. In the RNAi gene-knockdown experiments, we found that only the Cmix had any effect on sexually dimorphic morphology, and these mimicked the effects of Cmdsx knockdown in females. Knockdown of CmSxl had no measurable effects on stag beetle phenotype, while knockdown of Cmtra2 resulted in complete lethality at the prepupal period. These results indicate that the roles of CmSxl and Cmtra2 in the sex determination cascade are likely to have diverged in stag beetles when compared to Drosophila. Our results also suggest that Cmix has a conserved role in this pathway. In addition to those three genes, we also performed a more complete functional analysis of the C. metallifer dsx gene (Cmdsx) to identify the isoforms that regulate dimorphism more fully using exon-specific RNAi. We identified a total of 16 alternative splice variants of the Cmdsx gene that code for up to 14 separate exons. Despite the variation in RNA splice products of the Cmdsx gene, only four protein isoforms are predicted. The results of our exon-specific RNAi indicated that the essential CmDsx isoform for postembryonic male differentiation is CmDsxB, whereas postembryonic female specific differentiation is mainly regulated by CmDsxD. CONCLUSIONS: Taken together, our results highlight the importance of studying the function of highly conserved sex determination pathways in numerous insect species, especially those with dramatic and exaggerated sexual dimorphism, because conservation in protein structure does not always translate into conservation in downstream function. PMID- 27001108 TI - Neural arch tuberculosis of cervical spine causing compression of spinal cord. PMID- 27001109 TI - Inferior accessory ossicle of the anterior arch of the atlas in a trauma patient. PMID- 27001107 TI - Achieving change in primary care--causes of the evidence to practice gap: systematic reviews of reviews. AB - BACKGROUND: This study is to identify, summarise and synthesise literature on the causes of the evidence to practice gap for complex interventions in primary care. DESIGN: This study is a systematic review of reviews. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane Library and PsychINFO were searched, from inception to December 2013. Eligible reviews addressed causes of the evidence to practice gap in primary care in developed countries. Data from included reviews were extracted and synthesised using guidelines for meta-synthesis. RESULTS: Seventy reviews fulfilled the inclusion criteria and encompassed a wide range of topics, e.g. guideline implementation, integration of new roles, technology implementation, public health and preventative medicine. None of the included papers used the term "cause" or stated an intention to investigate causes at all. A descriptive approach was often used, and the included papers expressed "causes" in terms of "barriers and facilitators" to implementation. We developed a four-level framework covering external context, organisation, professionals and intervention. External contextual factors included policies, incentivisation structures, dominant paradigms, stakeholders' buy-in, infrastructure and advances in technology. Organisation-related factors included culture, available resources, integration with existing processes, relationships, skill mix and staff involvement. At the level of individual professionals, professional role, underlying philosophy of care and competencies were important. Characteristics of the intervention that impacted on implementation included evidence of benefit, ease of use and adaptability to local circumstances. We postulate that the "fit" between the intervention and the context is critical in determining the success of implementation. CONCLUSIONS: This comprehensive review of reviews summarises current knowledge on the barriers and facilitators to implementation of diverse complex interventions in primary care. To maximise the uptake of complex interventions in primary care, health care professionals and commissioning organisations should consider the range of contextual factors, remaining aware of the dynamic nature of context. Future studies should place an emphasis on describing context and articulating the relationships between the factors identified here. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009410. PMID- 27001110 TI - 18F-fluorodeoxyglucose-positron emission tomography avid paraspinal soft-tissue mass mimicking a malign neoplasm: non-traumatic myositis ossificans. PMID- 27001111 TI - Idiopathic transdural spinal cord herniation. PMID- 27001112 TI - Paraplegia caused by thoracic fracture dislocation in a young patient and management: case report. PMID- 27001113 TI - Kummell disease: illustrative case for definition criteria. PMID- 27001114 TI - Stability of the cytoskeleton of matured buffalo oocytes pretreated with cytochalasin B prior to vitrification. AB - Stabilizing the cytoskeleton system during vitrification can improve the post thaw survival and development of vitrified oocytes. The cytoskeleton stabilizer cytochalasin B (CB) has been used in cryopreservation to improve the developmental competence of vitrified oocytes. To assess the effect of pretreating matured buffalo oocytes with CB before vitrification, we applied 0, 4, 8, or 12 MUg/mL CB for 30 min. The optimum concentration of CB treatment (8 MUg/mL for 30 min) was then used to evaluate the distribution of microtubules and microfilaments, the expression of the cytoskeleton proteins actin and tubulin, and the developmental potential of matured oocytes that were vitrified-warmed by the Cryotop method. Western blotting demonstrated that vitrification significantly decreased tubulin expression, but that the decrease was attenuated for oocytes pretreated with 8 MUg/mL CB before vitrification. After warming and intracytoplasmic sperm injection, oocytes that were pretreated with 8 MUg/mL CB before vitrification yielded significantly higher 8-cell and blastocyst rates than those that were vitrified without CB pretreatment. The values for the vitrified groups in all experiments were significantly lower (P < 0.01) than those of the control groups. In conclusion, pretreatment with 8 MUg/mL CB for 30 min significantly improves the cytoskeletal structure, expression of tubulin, and development capacity of vitrified matured buffalo oocytes. PMID- 27001115 TI - The Risk of Developing Diabetes in Association With Long Working Hours Differs by Shift Work Schedules. AB - BACKGROUND: The impact of long working hours on diabetes is controversial; however, shift work is known to increase the risk of diabetes. This study aimed to investigate the association between long working hours and diabetes among civil servants in Japan separately by shift work schedules. METHODS: A prospective cohort study was conducted from April 2003 to March 2009. A total of 3195 men aged >=35 years who underwent an annual health checkup at baseline were analyzed by shift work schedules (2371 non-shift workers and 824 shift workers). Self-reported working hours were categorized as 35-44 and >=45 hours per week. The incidence of diabetes was confirmed by fasting plasma glucose concentration >=126 mg/dL and/or self-reported medical diagnosis of diabetes at the annual checkup. A Cox proportional model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing diabetes associated with long working hours. RESULTS: The median follow-up period of non-shift and shift workers was 5.0 and 4.9 years, respectively. During this period, 138 non-shift workers and 46 shift workers developed diabetes. A decreased HR was found among non-shift workers working >=45 hours per week (HR 0.84; 95% CI, 0.57-1.24); however, shift workers working >=45 hours per week had a significantly increased risk of diabetes (HR 2.43; 95% CI, 1.21-5.10) compared with those working 35-44 hours per week. An analysis restricted to non-clerical workers also showed similar results. CONCLUSIONS: The risk of diabetes associated with long working hours differed by shift work schedules. PMID- 27001116 TI - Minimum Cost Estimation of a Baseline Survey for a Molecular Epidemiology Cohort Study: Collecting Participants in a Model Region in Japan. AB - BACKGROUND: Some recent molecular epidemiology studies of the effects of genetic and environmental factors on human health have required the enrollment of more than 100 000 participants and the involvement of regional study offices across the country. Although regional study office investigators play a critical role in these studies, including the acquisition of funds, this role is rarely discussed. METHODS: We first differentiated the functions of the regional and central study offices. We then investigated the minimum number of items required and approximate cost of a molecular epidemiology study enrolling 7400 participants from a model region with a population of 100 000 for a 4-year baseline survey using a standard protocol developed based on the protocol of Japan Public Health Center-based Prospective Study for the Next Generation. RESULTS: The functions of the regional study office were identified, and individual expenses were itemized. The total cost of the 4-year baseline survey was 153 million yen, excluding consumption tax. Accounting difficulties in conducting the survey were clarified. CONCLUSIONS: We investigated a standardized example of the tasks and total actual costs of a regional study office. Our approach is easy to utilize and will help improve the management of regional study offices in future molecular epidemiology studies. PMID- 27001117 TI - Preliminary evidence on the use of telehealth in an outpatient behavior clinic. AB - Previous studies have shown that telehealth can be an effective way to deliver behavior-analytic services. In this study, we provided a demonstration of the use of telehealth to assess and initiate treatment of problem behavior in an outpatient clinic. We coached parents of children with autism via telehealth to conduct functional analyses during 1 appointment that lasted 1 hr and subsequently coached them as they implemented functional communication training during 3 subsequent appointments (15 min each). Social functions were identified for most children, and problem behavior was reduced by an average of 65.1%. PMID- 27001118 TI - Association of thymidylate synthase polymorphisms with the tumor response to preoperative chemoradiotherapy in rectal cancer: a systematic review and meta analysis. AB - Preoperative chemoradiotherapy (pCRT) followed by surgery is currently the standard therapy for patients with locally advanced rectal cancer. It is very important to develop biomarkers to prior identify the patients who have a higher likelihood of responding to pCRT. Recently, a series of studies have been conducted to investigate the association of thymidylate synthase (TYMS) polymorphisms with the tumor response to pCRT in rectal cancer, but the results were not consistent and conclusive. In the present study, we performed a systematic literature search for relevant studies up to 30 March 2015 and conducted a meta-analysis to summarize and clarify the association between the TYMS polymorphisms and the tumor response to pCRT in rectal cancer. Finally, 7 studies containing 892 cases for TYMS 2R/3R polymorphism, 7 studies involving 715 cases for TYMS 1494del6 polymorphism and 6 studies containing 616 cases for TYMS 5' untranslated region (UTR) expression allele polymorphism were analyzed in the meta-analysis. The results suggested that TYMS 2R/3R was associated with the response and the patients with 2R/2R or 2R/3R genotype with rectal cancer might benefit more from pCRT than others. On the contrary, neither 1494del6 nor 5'UTR expression allele polymorphisms was associated with the response to pCRT. PMID- 27001119 TI - Response to interferon-beta treatment in multiple sclerosis patients: a genome wide association study. AB - Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-beta) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-beta treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-beta-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 * 10-6) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 * 10-5) and near ZNF697 (combined P-value 8.15 * 10-5). PMID- 27001120 TI - The impact of ABCC11 polymorphisms on the risk of early-onset fluoropyrimidine toxicity. AB - A missense variant (c.1637C>T, T546M) in ABCC11 encoding the MRP8 (multidrug resistance protein 8), a transporter of 5-fluorodeoxyuridine monophosphate, has been associated with an increased risk of 5-fluorouracil-related severe leukopenia. To validate this association, we investigated the impact of the ABCC11 variants c.1637C>T, c.538G>A and c.395+1087C>T on the risk of early-onset fluoropyrimidine-related toxicity in 514 cancer patients. The ABCC11 variant c.1637C>T was strongly associated with severe leukopenia in patients carrying risk variants in DPYD, encoding the key fluoropyrimidine-metabolizing enzyme dihydropyrimidine dehydrogenase (odds ratio (OR): 71.0; 95% confidence interval (CI): 2.5-2004.8; Pc.1637C>T*DPYD=0.013). In contrast, in patients without DPYD risk variants, no association with leukopenia (OR: 0.95; 95% CI: 0.34-2.6) or overall fluoropyrimidine-related toxicity (OR: 1.02; 95% CI: 0.5-2.1) was observed. Our study thus suggests that c.1637C>T affects fluoropyrimidine toxicity to leukocytes particularly in patients with high drug exposure, for example, because of reduced fluoropyrimidine catabolism. PMID- 27001121 TI - Variant alleles in factor V, prothrombin, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase and risk of thromboembolism in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab. AB - Single-nucleotide polymorphisms (SNPs) related to hereditary thrombophilia were investigated as risk factors for thromboembolism in cancer patients. Their effect in metastatic colorectal cancer (mCRC) has never been explored so far. Our aim was to analyse the effect of coagulation factor V (FVL G1691A), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and plasminogen activator inhibitor type 1 (PAI-1 5G/4G) allelic variants in this setting. Fifty-two patients treated with first-line chemotherapy plus bevacizumab who developed a thromboembolic event in their lifetime were initially genotyped. A contemporary cohort of 127 patients who did not experience any thromboembolic event was also analysed. DNA was extracted from peripheral blood and genotypes were determined by real-time PCR, using LightSNiP (TIB MOLBIOL) on LightCcler 480 (Roche). The association between thromboembolism and SNPs was investigated by univariable and multivariable analyses. All SNPs were in Hardy-Weinberg equilibrium (chi2 test P>0.20). FVL G1691A and PT G20210A were present only in heterozygosis in 4 (2.2%) and 7 (3.9%) patients, respectively; MTHFR C677T in homozygosis in 29 (16.2%), MTHFR A1298C in homozygosis in 13 (7.3%); PAI-1 5G/4G in 98 (54.7%) and 4G/4G in 41 (23%) patients. At univariable analysis, treatment duration was significantly associated with thromboembolism (P<0.001), whereas gender, age, obesity, platelets count and chemotherapy backbone were not. Similarly, FVL G1691A and PT G20210A as well as MTHFR C677T and PAI-1 4G allele were significantly associated, whereas MTHFR A1298C was not. At multivariable model including PT G20210A, MTHFR C677T and PAI-1 4G (age, obesity, treatment duration and chemotherapy backbone were included as adjustment factors), the three SNPs were significantlty associated with higher risk of thromboembolism (P=0.025, <0.0001 and P=0.033, respectively). Further validation studies are warranted in order to design a prospective trial of thromboprophylaxis in mCRC patients with high-risk genotypes. PMID- 27001123 TI - HSRPP 2016 Reading - Foreword. PMID- 27001124 TI - Abstracts of Papers Presented at the Health Services Research & Pharmacy Practice Conference, 7-8 April 2016, University of Reading, UK. PMID- 27001125 TI - Atrial Rate-Responsive Pacing and Incidence of Sustained Atrial Arrhythmias in Patients with Implantable Cardioverter Defibrillators. AB - BACKGROUND: Atrial rate-responsive pacing (RRP) has proved to be safe in pacemaker recipients with chronotropic incompetence. Although RRP is available in all current implantable cardioverter defibrillators (ICDs), the outcomes of this pacing mode in ICD patients are unknown. The aim is to evaluate the relationship between atrial RRP and atrial arrhythmias in ICD recipients. METHODS: Dual chamber and triple-chamber ICD patients were included in this multicenter cohort study. Patients with permanent atrial fibrillation (AF) or VVI pacing mode were excluded. The number and duration of atrial tachycardia (AT)/AF episodes were assessed. RESULTS: Data from 415 patients and 80,707 AT/AF episodes (median duration: 0.4 hours) were collected after a 21.3 +/- 14.1-month follow-up. Atrial RRP was programmed in 90 (21.7%) patients and was associated with a higher atrial pacing percentage in the overall study population (51.2 +/- 33.8% vs 18.4 +/- 25.7%, P < 0.001) and to a higher ventricular pacing percentage among dual chamber devices (22.3 +/- 37.6% vs 9.3 +/- 25%, P < 0.001). Independent factors associated with sustained AT/AF episodes (>23 hours) were previous AF (odds ratio [OR]: 7.98; 95% confidence interval [CI]: 4.11-15.47; P < 0.001) and atrial RRP (OR: 3.58; 95% CI: 1.82-7.03; P < 0.001). RRP was related to a lower sustained AT/AF episodes-free survival both in patients with a history of AF (43% vs 70%, P = 0.035) and without a history of AF (82% vs 97%, P = 0.004) at 2 years. CONCLUSIONS: Atrial RRP in ICD patients was related to a higher incidence of sustained atrial arrhythmias. This pacing mode may have an atrial proarrhythmic effect on ICD patients, especially among those with a history of AF. PMID- 27001122 TI - Mechanisms of the placebo effect in pain and psychiatric disorders. AB - Placebo effect research over the past 15 years has improved our understanding of how placebo treatments reduce patient symptoms. The expectation of symptom improvement is the primary factor underlying the placebo effect. Such expectations are shaped by past experiences, contextual cues and biological traits, which ultimately modulate one's degree of response to a placebo. The body of evidence that describes the physiology of the placebo effect has been derived from mechanistic studies primarily restricted to the setting of pain. Imaging findings support the role of endogenous opioid and dopaminergic networks in placebo analgesia in both healthy patients as well as patients with painful medical conditions. In patients with psychiatric illnesses such as anxiety disorders or depression, a vast overlap in neurological changes is observed in drug responders and placebo responders supporting the role of serotonergic networks in placebo response. Molecular techniques have been relatively underutilized in understanding the placebo effect until recently. We present an overview of the placebo responder phenotypes and genetic markers that have been associated with the placebo effect in pain, schizophrenia, anxiety disorders and depression. PMID- 27001126 TI - Functional proteomics within the genus Lactobacillus. AB - Lactobacillus are mainly used for the manufacture of fermented dairy, sourdough, meat, and vegetable foods or used as probiotics. Under optimal processing conditions, Lactobacillus strains contribute to food functionality through their enzyme portfolio and the release of metabolites. An extensive genomic diversity analysis was conducted to elucidate the core features of the genus Lactobacillus, and to provide a better comprehension of niche adaptation of the strains. However, proteomics is an indispensable "omics" science to elucidate the proteome diversity, and the mechanisms of regulation and adaptation of Lactobacillus strains. This review focuses on the novel and comprehensive knowledge of functional proteomics and metaproteomics of Lactobacillus species. A large list of proteomic case studies of different Lactobacillus species is provided to illustrate the adaptability of the main metabolic pathways (e.g., carbohydrate transport and metabolism, pyruvate metabolism, proteolytic system, amino acid metabolism, and protein synthesis) to various life conditions. These investigations have highlighted that lactobacilli modulate the level of a complex panel of proteins to growth/survive in different ecological niches. In addition to the general regulation and stress response, specific metabolic pathways can be switched on and off, modifying the behavior of the strains. PMID- 27001127 TI - The proteome profile of embryogenic cell suspensions of Coffea arabica L. AB - Somatic embryogenesis, is a process by which new viable embryos are produced from somatic tissues. Somatic embryogenesis is not only a useful biotechnological tool for the massive clonal propagation and genetic engineering but it also allows to obtain fundamental knowledge about the molecular changes that take place during embryogenesis. We present the proteome profile of two embryogenic cell suspensions. We identified 1052 non-redundant proteins. We present their known GO annotations and show two protein networks sharing the GO annotations related to stress and embryogenic capacity via the free program Cytoscape. To our knowledge these results give the first high-throughput proteome description of embryogenic cell suspensions and provide new information about somatic embryos for the whole plant community. The published proteome is a first step toward understanding somatic embryogenesis in coffee and toward a better annotation of proteins in an important non-model crop. All data are available via ProteomeXchange with identifier PXD002963. PMID- 27001128 TI - Emergent geometries and nonlinear-wave dynamics in photon fluids. AB - Nonlinear waves in defocusing media are investigated in the framework of the hydrodynamic description of light as a photon fluid. The observations are interpreted in terms of an emergent curved spacetime generated by the waves themselves, which fully determines their dynamics. The spacetime geometry emerges naturally as a result of the nonlinear interaction between the waves and the self induced background flow. In particular, as observed in real fluids, different points of the wave profile propagate at different velocities leading to the self steepening of the wave front and to the formation of a shock. This phenomenon can be associated to a curvature singularity of the emergent metric. Our analysis offers an alternative insight into the problem of shock formation and provides a demonstration of an analogue gravity model that goes beyond the kinematic level. PMID- 27001129 TI - Using primate neural stem cells cultured in self-assembling peptide nanofiber scaffolds to repair injured spinal cords in rats. AB - STUDY DESIGN: Transplanted primates' neural stem cells (NSCs) tissue engineering complex into spinal cord injury (SCI) model rats, analyze and evaluate the long term effects of repairing. OBJECTIVES: Primate NSCs were cultured in self assembling peptide nanofiber scaffolds to repair SCI. SETTING: Sun Yat-sen Memorial Hospital, Guangzhou, China. METHODS: Primate NSCs were isolated and cultured in self-assembling peptide nanofiber scaffolds. T10 SCI model was established; the rats were randomly divided into four groups: NSC plus self assembling peptide scaffold group; NSC group; self-assembling peptide scaffold group; and control group. Immunohistochemical staining and electronic microscope were used to investigate the growth and differentiation of transplanted NSCs. The motor function of the hind limbs of rats was evaluated (P<0.05 was considered as statistically significant). RESULTS: NSCs and NSCs cultured in self-assembling peptide nanofiber scaffolds could be induced to differentiation into neurons, glial cells and oligodendrocytes in vitro. The primate NSC culture was established in self-assembling peptide scaffolds. No significant difference was seen in the differentiation rate between primate NSCs cultured in self-assembling peptide nanofiber scaffolds and primate NSCs cultured in regular medium. The motor function of the hind limbs in the NSC plus self-assembling peptide scaffold group was significantly better than that of the other three groups. In addition, the NSCs of the NSC group mainly differentiated into astrocytes. CONCLUSION: Transplantation of primate NSCs cultured in self-assembling peptide scaffolds is efficient for repairing the injured spinal cord and for improving the motor function of spinal cord in rats. SPONSORSHIP: The National Natural Science Foundation of China; Science and Technology Office of Guangdong Province. PMID- 27001130 TI - Family caregivers of individuals with spinal cord injury: exploring the stresses and benefits. AB - STUDY DESIGN: Cross-sectional, focus group. OBJECTIVES: To explore positive and negative issues reported by family caregivers of people with spinal cord injury (SCI) to develop a relevant and valid tool to assess caregiver distress and benefit for this unique population. METHODS: Seventy-three family caregivers of people with SCI participated in 16 focus groups. We audio-recorded all focus group discussions and transcribed the recordings verbatim. Qualitative analysis of the transcripts was performed to identify major themes and subthemes relating to family caregiving activities. RESULTS: Positive themes were disproportionately limited in comparison with negative themes. Positives included changes in self awareness, enhanced family cohesiveness and feeling appreciated. Negative themes included physical and emotional strain, dissatisfaction with hired carers and strain on family relationships. Health-related themes included fatigue and lack of sleep. Caregivers identified sources of strength that helped them manage stresses including faith and support from friends and co-workers. CONCLUSION: The numerous themes help lay the groundwork to develop a valid and reliable assessment tool to assist health-care providers in treatment planning and the provision of long-term assistance to people with SCI by enhancing areas of strengths and addressing factors that contribute to burden and distress for family caregivers. PMID- 27001131 TI - Bacterial susceptibility patterns in patients with spinal cord injury and disorder (SCI/D): an opportunity for customized stewardship tools. AB - STUDY DESIGN: Retrospective observational study of bacterial susceptibilities in Veterans with SCI/D as compared to a general patient population. OBJECTIVES: The purpose of this project was to evaluate the prevalence and susceptibility of bacteria isolated from spinal cord injury and disorder (SCI/D) patients as compared with a general patient population and determine whether a SCI/D-specific antibiogram, a report of bacterial susceptibilities used to guide empiric antibiotic selection, would be a useful stewardship tool. SETTING: Veterans Affairs Medical Center located in Cook county, IL, USA. METHODS: Microbiology reports from 1 October 2012 to 30 September 2013 were compiled into a SCI/D specific antibiogram and compared to a non-SCI/D antibiogram. RESULTS: Persons with positive cultures and SCI/D were younger and had a higher Charlson Index as compared to non-SCI/D patients (P<0.0001 for both). Five thousand one hundred and thirty-one unique isolate cultures were evaluated (SCI/D=23.0%). Frequencies of pathogens isolated in SCI/D and non-SCI/D differed. Methicillin-resistant Staphylococcus aureus occurred more frequently in SCI/D (27.8% vs 55.4%; P<0.0001). Gram-negatives had generally lower susceptibilities in SCI/D and a higher frequency of organisms producing extended-spectrum Beta-lactamases (17.6% vs 5.0%; P<0.0001), carbapenem-resistant Enterobacteriaceae (2.4% vs 0.5%; P<0.0001), carbapenem resistance (7.6% vs 2.4%; P<0.0001) and isolates resistant to ?3 antibiotic classes (60.7% vs 28.0%; P=0.0001). CONCLUSION: Different pathogens with poorer susceptibilities are isolated in SCI/D. Thus an SCI/D specific antibiogram reflective of resistance patterns in these patients may increase the appropriateness of empiric antibiotic selection. The frequency of multi-drug resistant organisms in cultures obtained from patients with SCI/D is worrisome. PMID- 27001132 TI - An audit of demographics and rehabilitation outcomes in non-traumatic spinal cord injury. AB - STUDY DESIGN: Repeated measures, retrospective cohort study. OBJECTIVES: To classify specific causes of injury in a cohort of non-traumatic spinal cord injury (NTSCI) patients, with the aim of exploring whether there are differences in demographics or rehabilitation outcomes depending on the cause of NTSCI. SETTING: Tertiary care, spinal cord injury rehabilitation unit. METHODS: Patients admitted to the unit with a non-traumatic SCI between July 2008 and April 2015 were considered for this study. Demographic information and rehabilitation outcomes were obtained from the Needs Assessment Checklist (NAC). NAC1 is completed within 4 weeks post mobilisation and NAC2 upon the patient moving to the pre-discharge ward. Data were obtained for 265 patients. RESULTS: The most common causes were vertebral column degenerative disorders, infection and vascular disorders, which together accounted for 80% of all NTSCI in this sample. Patients with vertebral column degenerative disorders were less likely to have a complete injury than patients with infections or vascular disorders. There were differences in rehabilitation outcomes on several domains of the NAC. Overall, patients with an SCI caused by an infection have the highest needs (more dependent), and patients with vertebral column degenerative disorders have the lowest needs (more independent). CONCLUSION: The relationship between non traumatic cause of injury and rehabilitation outcomes may be mediated by severity of injury. Individuals with infection-related NTSCI are more likely to be complete, therefore, present more significant rehab needs, and lower rehabilitation outcomes particularly in physical health, activities of daily living and bowel management domains. This supports previous findings of Kay et al. and provides a possible explanation for the differences. This further informs future interventions. PMID- 27001133 TI - Protein Kinase C Activation as a Potential Therapeutic Strategy in Alzheimer's Disease: Is there a Role for Embryonic Lethal Abnormal Vision-like Proteins? AB - Alzheimer's disease (AD), the most common cause of dementia, is an irreversible and progressive neurodegenerative disorder. It affects predominantly brain areas that are critical for memory and learning and is characterized by two main pathological hallmarks: extracellular amyloid plaques and intracellular neurofibrillary tangles. Protein kinase C (PKC) has been classified as one of the cognitive kinases controlling memory and learning. By regulating several signalling pathways involved in amyloid and tau pathologies, it also plays an inhibitory role in AD pathophysiology. Among downstream targets of PKC are the embryonic lethal abnormal vision (ELAV)-like RNA-binding proteins that modulate the stability and the translation of specific target mRNAs involved in synaptic remodelling linked to cognitive processes. This MiniReview summarizes the current evidence on the role of PKC and ELAV-like proteins in learning and memory, highlighting how their derangement can contribute to AD pathophysiology. This last aspect emphasizes the potential of pharmacological activation of PKC as a promising therapeutic strategy for the treatment of AD. PMID- 27001134 TI - Stereoarrayed CF3 -Substituted 1,3-Diols by Dynamic Kinetic Resolution: Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation. AB - CF3 -substituted 1,3-diols were stereoselectively prepared in excellent enantiopurity and high yield from CF3 -substituted diketones by using an ansa ruthenium(II)-catalyzed asymmetric transfer hydrogenation in formic acid/triethylamine. The intermediate mono-reduced alcohol was also obtained in very high enantiopurity by applying milder reaction conditions. In particular, CF3 C(O)-substituted benzofused cyclic ketones underwent either a single or a double dynamic kinetic resolution during their reduction. PMID- 27001135 TI - Does pedicle screw fixation under age 5 cause spinal canal narrowing? A CT study with minimum 5 years follow-up. AB - PURPOSE: The aim of this retrospective study was to evaluate the changes in the vertebral body and spinal canal area in a group of patients who had pedicle screw fixation under age 5 for the treatment of congenital spinal deformity at least 5 year follow-up. METHODS: 11 patients who had been operated due to spinal deformity under age 5 with who had a CT examination at least 5 years after the initial operation were included in the study. All patients underwent hemivertebrectomy and transpedicular fixation procedures at an average age of 3.18 years (range 2-5 years). All had preoperative CT to evaluate the congenital deformities. Measurements were done at the instrumented vertebrae as well as the un-instrumented ones above and below them to evaluate; vertebral body parameters, pedicle parameters and spinal canal area of upper instrumented vertebra (UIV), lower instrumented vertebra (LIV), upper adjacent un-instrumented vertebra and lower adjacent un-instrumented vertebra. RESULTS: The average follow-up was 7.2 (range 5-12) years. Six of the patients were over age 10 during the final CT examination while 5 were at age 7. Female-to male ratio was 8-3. Measurement of all the parameters in 22 instrumented and 22 non-instrumented segments showed a proportional increase rather than a decrease at each segment. The percentage of canal area growth at UIV and LIV was 21 and 17.5 %, respectively. CONCLUSION: Pedicle screw instrumentation has no adverse effect on further spinal body, pedicle and canal growth and does not result in iatrogenic spinal canal stenosis. PMID- 27001136 TI - Cost-effectiveness of manual therapy versus physiotherapy in patients with sub acute and chronic neck pain: a randomised controlled trial. AB - PURPOSE: To evaluate the cost-effectiveness of manual therapy according to the Utrecht School (MTU) in comparison with physiotherapy (PT) in sub-acute and chronic non-specific neck pain patients from a societal perspective. METHODS: An economic evaluation was conducted alongside a 52-week randomized controlled trial, in which 90 patients were randomized to the MTU group and 91 to the PT group. Clinical outcomes included perceived recovery (yes/no), functional status (continuous and yes/no), and quality-adjusted life-years (QALYs). Costs were measured from a societal perspective using self-reported questionnaires. Missing data were imputed using multiple imputation. To estimate statistical uncertainty, bootstrapping techniques were used. RESULTS: After 52 weeks, there were no significant between-group differences in clinical outcomes. During follow-up, intervention costs (beta:?-32; 95 %CI: -54 to -10) and healthcare costs (beta:? 126; 95 %CI: -235 to -32) were significantly lower in the MTU group than in the PT group, whereas unpaid productivity costs were significantly higher (beta:?186; 95 %CI:19-557). Societal costs did not significantly differ between groups (beta:?-96; 95 %CI:-1975-2022). For QALYs and functional status (yes/no), the maximum probability of MTU being cost-effective in comparison with PT was low (<=0.54). For perceived recovery (yes/no) and functional status (continuous), a large amount of money must be paid per additional unit of effect to reach a reasonable probability of cost-effectiveness. CONCLUSIONS: From a societal perspective, MTU was not cost-effective in comparison with PT in patients with sub-acute and chronic non-specific neck pain for perceived recovery, functional status, and QALYs. As no clear total societal cost and effect differences were found between MTU and PT, the decision about what intervention to administer, reimburse, and/or implement can be based on the preferences of the patient and the decision-maker at hand. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00713843. PMID- 27001137 TI - Accurate prediction of height loss in adolescent idiopathic scoliosis: Cobb angle alone is insufficient. AB - PURPOSE: Spinal height loss due to scoliosis was mostly calculated by equations with Cobb angle as the unique independent variable in adolescent idiopathic scoliosis (AIS), with their accuracy being seriously doubted. The purpose of this study was to compare and correlate the measured loss in spinal height (DeltaSHm) with the calculated loss in spinal height (DeltaSHc), and to identify the key factors associated with height loss in AIS. METHODS: This retrospective study included two stages. In stage I, 277 surgically treated AIS patients were reviewed, and divided into single curve and double curve groups. The accuracy and limitation of each correction equation was testified by comparing the data sets of DeltaSHc with the DeltaSHm, as well as comparing the pre- and post-op spinal length for each correction equation. In stage II, 235 curves within 100 AIS patients were selected to explore the relationship between loss in vertical curve height (?CH) and Cobb angle, curve length (CL), number of vertebrae within the curve (NVC), tilt angle of each curve (alpha) through partial correlation analysis. RESULTS: In stage I, the ?SHm averaged 3.5 cm in single curve group and 4.8 cm in double curve group. The DeltaSHc was only comparable with DeltaSHm using the Bjure's equation. Pre- and post-op spinal length was only comparable in Bjure's corrected group with Cobb angle <60 degrees (p > 0.05). In stage II, the partial correlation coefficients of ?CH with Cobb angle, CL, alpha, and NVC were 0.889, 0.493, -0.723 and -0.175 (p < 0.01), respectively. The ?CH could be calculated by the following formula: ?CH (mm) = 29.305 + 0.506Cobb + 0.083CL - 0.592alpha - 0.796NVC. CONCLUSIONS: Previous height correction equations employing Cobb angle as the unique independent variable are inaccurate. Cobb angle, curve length, curve inclination, and number of vertebrae within the curve are all strong determinants responsible for the height loss in AIS. PMID- 27001138 TI - Microendoscopic discectomy versus open discectomy for lumbar disc herniation: a meta-analysis. AB - PURPOSE: To compare the outcomes of microendoscopic discectomy and open discectomy for patients with lumbar disc herniation. METHODS: An extensive search of studies was performed in PubMed, Medline, Embase, Cochrane library and Google Scholar. The following outcome measures were extracted: visual analogue scale (VAS), Oswestry disability index (ODI), complication, operation time, blood loss and length of hospital stay. Data analysis was conducted with RevMan 5.0. RESULTS: Five randomized controlled trials involving 501 patients were included in this meta-analysis. The pooled analysis showed that there was no significant difference in the VAS, ODI or complication between the two groups. However, compared with the open discectomy, the microendoscopic discectomy was associated with less blood loss [WMD = -151.01 (-288.22, -13.80), P = 0.03], shorter length of hospital stay [WMD = -69.33 (-110.39, -28.28), P = 0.0009], and longer operation time [WMD = 18.80 (7.83, 29.76), P = 0.0008]. CONCLUSIONS: Microendoscopic discectomy, which requires a demanding learning curve, may be a safe and effective alternative to conventional open discectomy for patients with lumbar disc herniation. PMID- 27001139 TI - Mitragynine (Kratom) - monitoring in sports drug testing. AB - In 2014, mitragynine (Kratom) was placed on the Monitoring List of the World Anti Doping Agency to gain information of its current use in professional sports. Therefore, analytical strategies in sports drug testing are presented and the first Kratom case in professional sports is described. It is outlined that thorough monitoring by anti-doping laboratories is of utmost importance to obtain data on Kratom's misuse and to protect athletes from potential health hazards. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001141 TI - Global spatial ecology of three closely-related gadfly petrels. AB - The conservation status and taxonomy of the three gadfly petrels that breed in Macaronesia is still discussed partly due to the scarce information on their spatial ecology. Using geolocator and capture-mark-recapture data, we examined phenology, natal philopatry and breeding-site fidelity, year-round distribution, habitat usage and at-sea activity of the three closely-related gadfly petrels that breed in Macaronesia: Zino's petrel Pterodroma madeira, Desertas petrel P. deserta and Cape Verde petrel P. feae. All P. feae remained around the breeding area during their non-breeding season, whereas P. madeira and P. deserta dispersed far from their colony, migrating either to the Cape Verde region, further south to equatorial waters in the central Atlantic, or to the Brazil Current. The three taxa displayed a clear allochrony in timing of breeding. Habitat modelling and at-sea activity patterns highlighted similar environmental preferences and foraging behaviours of the three taxa. Finally, no chick or adult was recaptured away from its natal site and survival estimates were relatively high at all study sites, indicating strong philopatry and breeding-site fidelity for the three taxa. The combination of high philopatry, marked breeding asynchrony and substantial spatio-temporal segregation of their year-round distribution suggest very limited gene flow among the three taxa. PMID- 27001140 TI - Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes. AB - Hydrogel precursors are liquid solutions that are prone to leaking after surgical placement. This problem was overcome by incorporating either decellularized cartilage (DCC) or devitalized cartilage (DVC) microparticles into traditional photocrosslinkable hydrogel precursors in an effort to achieve a paste-like hydrogel precursor. DCC and DVC were selected specifically for their potential to induce chondrogenesis of stem cells, given that materials that are chondroinductive on their own without growth factors are a revolutionary goal in orthopedic medicine. We hypothesized that DVC, lacking the additional chemical processing steps in DCC to remove cell content, would lead to a more chondroinductive hydrogel with rat bone marrow-derived mesenchymal stem cells. Hydrogels composed of methacrylated hyaluronic acid (MeHA) and either DCC or DVC microparticles were tested with and without exposure to transforming growth factor (TGF)-beta3 over a 6 week culture period, where swelling, mechanical analysis, and gene expression were observed. For collagen II, Sox-9, and aggrecan expression, MeHA precursors containing DVC consistently outperformed the DCC containing groups, even when the DCC groups were exposed to TGF-beta3. DVC consistently outperformed all TGF-beta3-exposed groups in aggrecan and collagen II gene expression as well. In addition, when the same concentrations of MeHA with DCC or DVC microparticles were evaluated for yield stress, the yield stress with the DVC microparticles was 2.7 times greater. Furthermore, the only MeHA containing group that exhibited shape retention was the group containing DVC microparticles. DVC appeared to be superior to DCC in both chondroinductivity and rheological performance of hydrogel precursors, and therefore DVC microparticles may hold translational potential for cartilage regeneration. PMID- 27001142 TI - Evolutionary loss of light-harvesting proteins Lhcb6 and Lhcb3 in major land plant groups--break-up of current dogma. AB - Photosynthesis in plants and algae relies on the coordinated function of photosystems (PS) I and II. Their efficiency is augmented by finely-tuned light harvesting proteins (Lhcs) connected to them. The most recent Lhcs (in evolutionary terms), Lhcb6 and Lhcb3, evolved during the transition of plants from water to land and have so far been considered to be an essential characteristic of land plants. We used single particle electron microscopy and sequence analysis to study architecture and composition of PSII supercomplex from Norway spruce and related species. We have found that there are major land plant families that lack functional lhcb6 and lhcb3 genes, which notably changes the organization of PSII supercomplexes. The Lhcb6 and Lhcb3 proteins have been lost in the gymnosperm genera Picea and Pinus (family Pinaceae) and Gnetum (Gnetales). We also revealed that the absence of these proteins in Norway spruce modifies the PSII supercomplex in such a way that it resembles its counterpart in the alga Chlamydomonas reinhardtii, an evolutionarily older organism. Our results break a deep-rooted concept of Lhcb6 and Lhcb3 proteins being the essential characteristic of land plants, and beg the question of what the evolutionary benefit of their loss could be. PMID- 27001143 TI - Giant Enhancement of Internal Electric Field Boosting Bulk Charge Separation for Photocatalysis. AB - Incorporating carbon into Bi3 O4 Cl enhances its internal electric field by 126 times, which induces a bulk charge separation efficiency (etabulk ) of 80%. This ultrahigh etabulk value presents a state-of-the-art result in tuning the bulk charge separation. The generated C-doped Bi3 O4 Cl has a noble-metal- and electron-scavenger-free water-oxidation ability under visible light, which is difficult to achieve with most existing photocatalysts. PMID- 27001144 TI - Plasmodium falciparum infection and age influence parasite growth inhibition mediated by IgG in Beninese infants. AB - Antibodies that impede the invasion of Plasmodium falciparum (P. falciparum) merozoites into erythrocytes play a critical role in anti-malarial immunity. The Growth Inhibition Assay (GIA) is an in vitro measure of the functional capacity of such antibodies to limit erythrocyte invasion and/or parasite growth. Up to now, it is unclear whether growth-inhibitory activity correlates with protection from clinical disease and there are inconsistent results from studies performed with GIA. Studies that have focused on the relationship between IgGs and their in vitro parasite Growth Inhibition Activity (GIAc) in infants aged less than two years old are rare. Here, we used clinical and parasitological data to precisely define symptomatic or asymptomatic infection with P. falciparum in groups of infants followed-up actively for 18 months post-natally. We quantified the levels of IgG1 and IgG3 directed to a panel of candidate P. falciparum vaccine antigens (AMA-1, MSP1, 2, 3 and GLURP) using ELISA and the functional activity of IgG was quantified using GIA. Data were then correlated with individuals' infection status. At 18 months of age, infants harbouring infections at the time of blood sampling had an average 19% less GIAc than those not infected (p=0.004, multivariate linear regression). GIAc decreased from 12 to 18 months of age (p=0.003, Wilcoxon matched pairs test). Antibody levels quantified at 18 months in infants were strongly correlated with their exposure to malarial infection, however GIAc was not correlated with malaria infectious status (asymptomatic and symptomatic groups). In conclusion, both infection status at blood draw and age influence parasite growth inhibition mediated by IgG in the GIA. Both factors must be taken into account when correlations between GIAc and anti-malarial protection or vaccine efficacy have to be made. PMID- 27001146 TI - Matrix metalloproteinase-13 participates in neuroprotection and neurorepair after cerebral ischemia in mice. AB - New neuroreparative and neuroprotective therapies are being sought to treat stroke patients. One approach is the remodeling of extracellular matrix, which participates in both brain injury and neurovascular repair when matrix metalloproteinases (MMPs) are thought to be key players. Our aim was to investigate the role of MMP-13 (collagenase-3) in the acute (24h and 3days) and delayed (2weeks) phases of stroke. Permanent and transient cerebral ischemia models involving the cortex were induced in MMP-13 knock-out (KO) and wild-type (WT) mice. In the transient model, MMP-13 deficiency reduced the amount of TTC stained infarct tissue, reduced hemorrhagic events and improved functional outcomes (p<0.01). At two weeks, normal neuroblast (DCX+) migration from the subventricular zone toward the peri-infarct area was observed. However, MMP-13 deficiency significantly reduced the number of newborn neuroblasts (DCX+/BrdU+) in the cortical peri-infarct area (p<0.01). This result occurred in parallel with aberrant cortical vascular remodeling: post-stroke peri-infarct vessel density increased in the WT mice (p<0.01) but this increase was blocked in the MMP-13 KO mice. Prior to these vascular alterations, the levels of pro-angiogenic factors, including G-CSF, VEGF-A and angiopoietin-2, were lower in the ischemic cortex of MMP-13 KO mice than in WT mice (p<0.05). In vitro, gene-silencing of MMP-13 in endothelial progenitor cells (EPCs) confirmed the reduced ability of these cells to build tubulogenic networks in MatrigelTM substrate. Together, our results indicate that MMP-13 is a central protease in infarct development and cortical remodeling during post-stroke neurorepair, which is critical for optimal angiogenic and neurogenic responses. PMID- 27001145 TI - Malaria and HIV among pediatric inpatients in two Tanzanian referral hospitals: A prospective study. AB - Malaria remains common in sub-Saharan Africa, but it is frequently over-diagnosed and over-treated in hospitalized children. HIV is prevalent in many malaria endemic areas and may delay parasite clearance and increase mortality among children with malaria. This prospective cohort study enrolled children with suspected malaria between 3 months and 12 years of age hospitalized at two referral hospitals in Tanzania. Both a thick blood smear (BS) and a malaria rapid diagnostic test (mRDT) were performed. If discordant results were obtained, PCR was performed for Plasmodium falciparum. Malaria was confirmed if two out of three tests were positive. Malaria parasite densities were determined for two consecutive days after diagnosis and treatment of malaria. All participants were tested for HIV. Among 1492 hospitalized children, 400 (26.8%) were enrolled with suspected malaria infection. There were 196/400 (49.0%) males, and the median age was 18 [9-36] months. BS was positive in 95/400 (23.8%), and mRDT was positive in 70/400 (17.5%), with moderate agreement (Kappa=0.598). Concordant results excluded malaria in 291/400 (72.8%) and confirmed malaria in 56/400 (14.0%). PCR performed on 53 discordant results confirmed malaria in 1/39 of the BS positive/mRDT-negative cases, and 6/14 of the BS-negative/mRDT-positive cases. The prevalence of confirmed malaria was 63/400 (15.8%). In multivariable logistic regression, malaria was associated with HIV (OR 3.45 [1.65-7.20], p=0.001). Current breastfeeding (OR 0.25 [0.11-0.56], p=0.001) and higher hemoglobin (OR 0.70 [0.60-0.81], p<0.001 per 1g/dL) were associated with decreased odds of malaria. Malaria parasite clearance was delayed in HIV-infected participants (p<0.001). Malaria is over-diagnosed even at referral centers in high transmission areas. Hospitalized HIV-infected children are more likely to have malaria and exhibit delayed clearance of parasites. Hospitals should consider using mRDTs as a first step for malaria testing among hospitalized children in sub-Saharan Africa. PMID- 27001147 TI - Neuronal deficiency of HIF prolyl 4-hydroxylase 2 in mice improves ischemic stroke recovery in an HIF dependent manner. AB - Hypoxia inducible factors (HIFs) mediate the endogenous adaptive responses to hypoxia. HIF prolyl 4-hydroxylase domain proteins (PHD) are important suppressors of the HIF pathway. Recently, we demonstrated that neuron-specific deletion of Phd2 reduces cerebral tissue damage in the very acute phase of ischemic stroke. In the present study, we investigated whether neuronal Phd2 ablation is likewise beneficial for stroke recovery, and aimed to identify underlying cellular mechanisms. Mice underwent permanent occlusion of the distal middle cerebral artery (pdMCAO) for either 7days (sub-acute stage) or 30days (chronic stage). One week after pdMCAO the infarct size of Phd2-deficient mice was significantly reduced as compared to wild-type (WT) mice. Accordingly, Phd2-deficient animals showed less impaired sensorimotor function. Neuronal loss of Phd2 upregulated vascular endothelial growth factor (VEGF) and significantly increased microvascular density along the infarct border in the sub-acute stage of stroke. Phd2-deficient mice showed reduced expression of pro-inflammatory cytokines and increased numbers of resting microglia/macrophages and reactive astrocytes within peri-infarct regions in comparison to WT littermates. Finally, brain tissue protection and increased angiogenesis upon sub-acute ischemic stroke was completely absent in Phd2 knockout mice that were additionally deficient for both Hif1a and Hif2a. Our findings suggest that lack of PHD2 in neurons improves histological and functional long-term outcome from ischemic stroke at least partly by amplifying endogenous adaptive neovascularization through activation of the HIF-VEGF axis. PMID- 27001149 TI - Role of histone acetylation in long-term neurobehavioral effects of neonatal Exposure to sevoflurane in rats. AB - Human studies, and especially laboratory studies, provide evidence that early life exposure to general anesthesia may affect neurocognitive development via largely unknown mechanisms. We explored whether hippocampal histone acetylation had a role in neurodevelopmental effects of sevoflurane administered to neonatal rats. Male Sprague-Dawley rats were exposed to 3% sevoflurane or were subjected to maternal separation only for 2h daily at postnatal days 6, 7, and 8. The histone deacetylase inhibitor, sodium butyrate (250mg/kg, intraperitoneally), or saline was administered starting 2h prior to anesthesia or maternal separation and continued daily until the end of behavioral tests, which were performed between postnatal days 33 and 50. Upon completion of the behavioral tests, the brain tissues were harvested for further analysis. Rats neonatally exposed to sevoflurane exhibited decreased freezing time in the fear conditioning contextual test and increased escape latency, decreased time in target quadrant, and number of platform crossings in the Morris water maze test. The sevoflurane-exposed rats had lower hippocampal density of dendritic spines, reduced levels of the brain derived neurotrophic factor, c-fos protein, microtubule-associated protein 2, synapsin1, postsynaptic density protein 95, pCREB/CREB, CREB binding protein, and acetylated histones H3 and H4, and increased levels of histone deacetylases 3 and 8. These neurobehavioral abnormalities were normalized in the sevoflurane-exposed rats treated with sodium butyrate. Our findings provide evidence that neonatal exposure to sevoflurane induces neurobehavioral abnormalities and long-lasting alterations in histone acetylation; normalization of histone acetylation may alleviate the neurodevelopmental side effects of the anesthetic. PMID- 27001150 TI - c-axis preferential orientation of hydroxyapatite accounts for the high wear resistance of the teeth of black carp (Mylopharyngodon piceus). AB - Biological armors such as mollusk shells have long been recognized and studied for their values in inspiring novel designs of engineering materials with higher toughness and strength. However, no material is invincible and biological armors also have their rivals. In this paper, our attention is focused on the teeth of black carp (Mylopharyngodon piceus) which is a predator of shelled mollusks like snails and mussels. Nanoscratching test on the enameloid, the outermost layer of the teeth, indicates that the natural occlusal surface (OS) has much higher wear resistance compared to the other sections. Subsequent X-ray diffraction analysis reveals that the hydroxyapatite (HAp) crystallites in the vicinity of OS possess c-axis preferential orientation. The superior wear resistance of black carp teeth is attributed to the c-axis preferential orientation of HAp near the OS since the (001) surface of HAp crystal, which is perpendicular to the c-axis, exhibits much better wear resistance compared to the other surfaces as demonstrated by the molecular dynamics simulation. Our results not only shed light on the origin of the good wear resistance exhibited by the black carp teeth but are of great value to the design of engineering materials with better abrasion resistance. PMID- 27001148 TI - Mic60/mitofilin overexpression alters mitochondrial dynamics and attenuates vulnerability of dopaminergic cells to dopamine and rotenone. AB - Mitochondrial dysfunction has been implicated in Parkinson's disease (PD) neuropathology. Mic60, also known as mitofilin, is a protein of the inner mitochondrial membrane and a key component of the mitochondrial contact site and cristae junction organizing system (MICOS). Mic60 is critical for maintaining mitochondrial membrane structure and function. We previously demonstrated that mitochondrial Mic60 protein is susceptible to both covalent modification and loss in abundance following exposure to dopamine quinone. In this study, we utilized neuronally-differentiated SH-SY5Y and PC12 dopaminergic cell lines to examine the effects of altered Mic60 levels on mitochondrial function and cellular vulnerability in response to PD-relevant stressors. Short hairpin RNA (shRNA) mediated knockdown of endogenous Mic60 protein in neuronal SH-SY5Y cells significantly potentiated dopamine-induced cell death, which was rescued by co expressing shRNA-insensitive Mic60. Conversely, in PC12 and SH-SY5Y cells, Mic60 overexpression significantly attenuated both dopamine- and rotenone-induced cell death as compared to controls. Mic60 overexpression in SH-SY5Y cells was also associated with increased mitochondrial respiration, and, following rotenone exposure, increased spare respiratory capacity. Mic60 knockdown cells exhibited suppressed respiration and, following rotenone treatment, decreased spare respiratory capacity. Mic60 overexpression also affected mitochondrial fission/fusion dynamics. PC12 cells overexpressing Mic60 exhibited increased mitochondrial interconnectivity. Further, both PC12 cells and primary rat cortical neurons overexpressing Mic60 displayed suppressed mitochondrial fission and increased mitochondrial length in neurites. These results suggest that altering levels of Mic60 in dopaminergic neuronal cells significantly affects both mitochondrial homeostasis and cellular vulnerability to the PD-relevant stressors dopamine and rotenone, carrying implications for PD pathogenesis. PMID- 27001153 TI - Breast Cancer Risk Variants Affect Estrogen Receptor. AB - Researchers have discovered five risk variants for breast cancer that lie in the vicinity of the gene that codes for the estrogen receptor. Four of the variants occur within enhancer regions and reduce expression of the receptor, and the fifth is in a silencer region and increases expression. PMID- 27001151 TI - Chromosomal Instability Affects the Tumorigenicity of Glioblastoma Tumor Initiating Cells. AB - Tumors are dynamic organs that evolve during disease progression with genetic, epigenetic, and environmental differences among tumor cells serving as the foundation for selection and evolution in tumors. Tumor-initiating cells (TIC) that are responsible for tumorigenesis are a source of functional cellular heterogeneity, whereas chromosomal instability (CIN) is a source of karyotypic genetic diversity. However, the extent that CIN contributes to TIC genetic diversity and its relationship to TIC function remains unclear. Here, we demonstrate that glioblastoma TICs display CIN with lagging chromosomes at anaphase and extensive nonclonal chromosome copy-number variations. Elevating the basal chromosome missegregation rate in TICs decreases both proliferation and the stem-like phenotype of TICs in vitro Consequently, tumor formation is abolished in an orthotopic mouse model. These results demonstrate that TICs generate genetic heterogeneity within tumors, but that TIC function is impaired if the rate of genetic change is elevated above a tolerable threshold. SIGNIFICANCE: Genetic heterogeneity among TICs may produce advantageous karyotypes that lead to therapy resistance and relapse; however, we found that TICs have an upper tolerable limit for CIN. Thus, increasing the chromosome missegregation rate offers a new therapeutic strategy to eliminate TICs from tumors. Cancer Discov; 6(5); 532-45. (c)2016 AACR.This article is highlighted in the In This Issue feature, p. 461. PMID- 27001154 TI - Maternal perception of weight status in first-born Australian toddlers aged 12-16 months--the NOURISH and SAIDI cohorts. AB - BACKGROUND: The preference amongst parents for heavier infants is in contrast to obesity prevention efforts worldwide. Parents are poor at identifying overweight in older children, but few studies have investigated maternal perception of weight status amongst toddlers and none in the Australian setting. METHODS: Mothers (n = 290) completed a self-administered questionnaire at child age 12-16 months, defining their child's weight status as underweight, normal weight, somewhat overweight or very overweight. Weight-for-length z-score was derived from measured weight and length, and children categorized as underweight, normal weight, at risk overweight or obese (WHO standards). Objective classification was compared with maternal perception of weight status. Mean weight-for-length z score was compared across categories of maternal perception using one-way ANOVA. Multinomial logistic regression was used to determine child or maternal characteristics associated with inaccurate weight perception. RESULTS: Most children (83%) were perceived as normal weight. Twenty nine were described as underweight, although none were. Sixty-six children were at risk of overweight, but 57 of these perceived as normal weight. Of the 14 children who were overweight, only 4 were identified as somewhat overweight by their mother. Compared with mothers who could accurately classify their normal weight child, mothers who were older had higher odds of perceiving their normal weight child as underweight, while mothers with higher body mass index had slightly higher odds of describing their overweight/at risk child as normal weight. CONCLUSION: The leaner but healthy weight toddler was perceived as underweight, while only the heaviest children were recognized as overweight. Mothers unable to accurately identify children at risk are unlikely to act to prevent further excess weight gain. Practitioners can lead a shift in attitudes towards weight in infants and young children, promoting routine growth monitoring and adequate but not rapid weight gain. PMID- 27001155 TI - Why should biochemistry students be introduced to molecular dynamics simulations- and how can we introduce them? AB - Molecular dynamics (MD) simulations play an increasingly important role in many aspects of biochemical research but are often not part of the biochemistry curricula at the undergraduate level. This article discusses the pedagogical value of exposing students to MD simulations and provides information to help instructors consider what software and hardware resources are necessary to successfully introduce these simulations into their courses. In addition, a brief review of the MD-based activities in this issue and other sources are provided. PMID- 27001157 TI - Airway smooth muscle enlargement is associated with protease-activated receptor 2/ligand overexpression in patients with difficult-to-control severe asthma. AB - BACKGROUND: Asthma is a complex disease with heterogeneous features of airway inflammation and remodeling. The increase in airway smooth muscle (ASM) mass is an essential component of airway remodeling in patients with severe asthma, yet the pathobiological mechanisms and clinical outcomes associated with ASM enlargement remain elusive. OBJECTIVE: We sought to compare ASM area in control subjects and patients with mild-to-moderate or severe asthma and to identify specific clinical and pathobiological characteristics associated with ASM enlargement. METHODS: Bronchial biopsy specimens from 12 control subjects, 24 patients with mild-to-moderate asthma, and 105 patients with severe asthma were analyzed for ASM area, basement membrane thickness, vessels, eosinophils, neutrophils, T lymphocytes, mast cells, and protease-activated receptor 2 (PAR 2). In parallel, the levels of several ASM mitogenic factors, including the PAR-2 ligands, mast cell tryptase, trypsin, tissue factor, and kallikrein (KLK) 5 and KLK14, were assessed in bronchoalveolar lavage fluid. Data were correlated with asthma severity and control both at inclusion and after 12 to 18 months of optimal management and therapy. RESULTS: Analyses across ASM quartiles in patients with severe asthma demonstrated that patients with the highest ASM quartile (median value of ASM area, 26.3%) were younger (42.5 vs >=50 years old in the other groups, P <= .04) and had lower asthma control after 1 year of optimal management (P <= .006). ASM enlargement occurred independently of features of airway inflammation and remodeling, whereas it was associated with PAR-2 overexpression and higher alveolar tryptase (P <= .02) and KLK14 (P <= .03) levels. CONCLUSION: Increase in ASM mass, possibly involving aberrant expression and activation of PAR-2-mediated pathways, characterizes younger patients with severe asthma with poor asthma control. PMID- 27001158 TI - Persistence of the IgE repertoire in birch pollen allergy. PMID- 27001159 TI - Segmental allergen challenge increases levels of airway follistatin-like 1 in patients with asthma. PMID- 27001161 TI - A novel viral RNA helicase with an independent translation enhancement activity. AB - RNA helicases have not been identified among negative sense RNA viruses. In this study, it is shown that Nonstructural protein (NSs) of Groundnut bud necrosis virus (GBNV) acts as a Mg(2+) - and ATP-dependent bipolar RNA helicase. Biophysical and biochemical analysis of the deletion mutants (NDelta124 NSs, CDelta80 NSs) revealed that both the N- and C-terminal residues are required for substrate binding, oligomerization and helicase activity, but are dispensable for ATPase activity. Interestingly, NSs could enhance the translation of RNA (~ 10 fold) independent of its helicase activity. This is the first report of a RNA helicase from negative strand RNA viruses. PMID- 27001160 TI - Aggregation of Chameleon Peptides: Implications of alpha-Helicity in Fibril Formation. AB - We investigate the relationship between the inherent secondary structure and aggregation propensity of peptides containing chameleon sequences (i.e., sequences that can adopt either alpha or beta structure depending on context) using a combination of replica exchange molecular dynamics simulations, ion mobility mass spectrometry, circular dichroism, and transmission electron microscopy. We focus on an eight-residue long chameleon sequence that can adopt an alpha-helical structure in the context of the iron-binding protein from Bacillus anthracis (PDB id 1JIG ) and a beta-strand in the context of the baculovirus P35 protein (PDB id 1P35 ). We show that the isolated chameleon sequence is intrinsically disordered, interconverting between alpha-helical and beta-rich conformations. The inherent conformational plasticity of the sequence can be constrained by addition of flanking residues with a given secondary structure propensity. Intriguingly, we show that the chameleon sequence with helical flanking residues aggregates rapidly into fibrils, whereas the chameleon sequence with flanking residues that favor beta-conformations has weak aggregation propensity. This work sheds new insights into the possible role of alpha-helical intermediates in fibril formation. PMID- 27001163 TI - Hodgkin lymphoma: 2016 update on diagnosis, risk-stratification, and management. AB - DISEASE OVERVIEW: Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 9,050 new patients annually and representing approximately 11.2% of all lymphomas in the United States. DIAGNOSIS: HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups under the designation of classical HL. RISK STRATIFICATION: An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. RISK-ADAPTED THERAPY: Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. PMID- 27001162 TI - Myocardial imaging using ultrahigh-resolution spectral domain optical coherence tomography. AB - We present an ultrahigh-resolution spectral domain optical coherence tomography (OCT) system in 800 nm with a low-noise supercontinuum source (SC) optimized for myocardial imaging. The system was demonstrated to have an axial resolution of 2.72 MUm with a large imaging depth of 1.78 mm and a 6-dB falloff range of 0.89 mm. The lateral resolution (5.52 MUm) was compromised to enhance the image penetration required for myocardial imaging. The noise of the SC source was analyzed extensively and an imaging protocol was proposed for SC-based OCT imaging with appreciable contrast. Three-dimensional datasets were acquired ex vivo on the endocardium side of tissue specimens from different chambers of fresh human and swine hearts. With the increased resolution and contrast, features such as elastic fibers, Purkinje fibers, and collagen fiber bundles were observed. The correlation between the structural information revealed in the OCT images and tissue pathology was discussed as well. PMID- 27001164 TI - Intermittent chaos in the Bray-Liebhafsky oscillator. Temperature dependence. AB - Intermittent oscillations as a chaotic mixture of large amplitude relaxation oscillations, grouped in bursts and small-amplitude sinusoidal ones or even quiescent parts between them known as gaps, were found and examined in the Bray Liebhafsky (BL) reaction performed in CSTR under controlled temperature variations. They were obtained in a narrow temperature range from 61.0 degrees C to 63.1 degrees C, where 61.0 degrees C is the critical temperature for burst emergence from the stable steady state and 63.1 degrees C is the critical temperature for gap emergence from regular oscillations. Since intermittencies appear gradually from the regular oscillatory state, and no hysteresis was obtained with decreasing/increasing temperature in the vicinity of these two bifurcations, a linear relationship between (tauB/tau)(2) and (tauG/tau)(2) (where tauB, tauG and tau denotes duration of bursts, gaps, and whole experiment, respectively), as a function of the temperature as the control parameter, was expected and obtained. Although these intermittent oscillations are chaotic with respect to the lengths of individual gaps as well as bursts, their deterministic behavior related to temperature was additionally established. Thus, the number of bursts or gaps per unit of time (NB/tau and NG/tau) has the form of a normal distribution function over the temperature range in the region where intermittencies are obtained. Temperature dependence of the Lyapunov exponents was also described by a function of the normal distribution form. Hence, we established some regularities in the chaotic behavior of intermittent oscillations that are common in life but difficult for determinations. PMID- 27001165 TI - Phenotypic plasticity of post-fire activity and thermal biology of a free-ranging small mammal. AB - Ecosystems can change rapidly and sometimes irreversibly due to a number of anthropogenic and natural factors, such as deforestation and fire. How individual animals exposed to such changes respond behaviourally and physiologically is poorly understood. We quantified the phenotypic plasticity of activity patterns and torpor use - a highly efficient energy conservation mechanism - in brown antechinus (Antechinus stuartii), a small Australian marsupial mammal. We compared groups in densely vegetated forest areas (pre-fire and control) with a group in a burned, open habitat (post-fire). Activity and torpor patterns differed among groups and sexes. Females in the post-fire group spent significantly less time active than the other groups, both during the day and night. However, in males only daytime activity declined in the post-fire group, although overall activity was also reduced on cold days in males for all groups. The reduction in total or diurnal activity in the post-fire group was made energetically possible by a ~3.4-fold and ~2.2-fold increase in the proportion of time females and males, respectively, used torpor in comparison to that in the pre-fire and control groups. Overall, likely due to reproductive needs, torpor was more pronounced in females than in males, but low ambient temperatures increased torpor bout duration in both sexes. Importantly, for both male and female antechinus and likely other small mammals, predator avoidance and energy conservation - achieved by reduced activity and increased torpor use - appear to be vital for post-fire survival where ground cover and refuges have been obliterated. PMID- 27001166 TI - Effect of Dust Storms on the Atmospheric Microbiome in the Eastern Mediterranean. AB - We evaluated the impact of Saharan dust storms on the local airborne microbiome in a city in the Eastern Mediterranean area. Samples of particles with diameter less than 10 MUm were collected during two spring seasons on both dusty and nondusty days. DNA was extracted, and partial 16S rRNA gene amplicons were sequenced using the Illumina platform. Bioinformatic analysis showed the effect of dust events on the diversity of the atmospheric microbiome. The relative abundance of desert soil-associated bacteria increased during dust events, while the relative abundance of anthropogenic-influenced taxa decreased. Quantitative polymerase chain reaction measurements of selected clinically significant antibiotic resistance genes (ARGs) showed that their relative abundance decreased during dust events. The ARG profiles on dust-free days were similar to those in aerosol collected in a poultry house, suggesting a strong agricultural influence on the local ambient profiles. We conclude that dust storms enrich the ambient airborne microbiome with new soil-derived bacteria that disappear as the dust settles, suggesting that the bacteria are transported attached to the dust particles. Dust storms do not seem to be an important vector for transport of probed ARGs. PMID- 27001167 TI - Improving neurosurgical communication and reducing risk and registrar burden using a novel online database referral platform. AB - OBJECTIVES: Documentation of urgent referrals to neurosurgical units and communication with referring hospitals is critical for effective handover and appropriate continuity of care within a tertiary service. Referrals to our neurosurgical unit were audited and we found that the majority of referrals were not documented and this led to more calls to the on-call neurosurgery registrar regarding old referrals. We implemented a new referral system in an attempt to improve documentation of referrals, communication with our referring hospitals and to professionalise the service we offer them. METHODS: During a 14-day period, number of bleeps, missed bleeps, calls discussing new referrals and previously processed referrals were recorded. Whether new referrals were appropriately documented and referrers received a written response was also recorded. A commercially provided secure cloud-based data archiving telecommunications and database platform for referrals was subsequently introduced within the Trust and the questionnaire repeated during another 14-day period 1 year after implementation. RESULTS: Missed bleeps per day reduced from 16% (SD +/- 6.4%) to 9% (SD +/- 4.8%; df = 13, paired t-tests p = 0.007) and mean calls per day clarifying previous referrals reduced from 10 (SD +/- 4) to 5 (SD +/- 3.5; df = 13, p = 0.003). Documentation of new referrals increased from 43% (74/174) to 85% (181/210), and responses to referrals increased from 74% to 98%. CONCLUSION: The use of a secure cloud-based data archiving telecommunications and database platform significantly increased the documentation of new referrals. This led to fewer missed bleeps and fewer calls about old referrals for the on call registrar. This system of documenting referrals results in improved continuity of care for neurosurgical patients, a significant reduction in risk for Trusts and a more efficient use of Registrar time. PMID- 27001168 TI - On the deep structure of social affect: Attitudes, emotions, sentiments, and the case of "contempt". AB - Contempt is typically studied as a uniquely human moral emotion. However, this approach has yielded inconclusive results. We argue this is because the folk affect concept "contempt" has been inaccurately mapped onto basic affect systems. "Contempt" has features that are inconsistent with a basic emotion, especially its protracted duration and frequently cold phenomenology. Yet other features are inconsistent with a basic attitude. Nonetheless, the features of "contempt" functionally cohere. To account for this, we revive and reconfigure the sentiment construct using the notion of evolved functional specialization. We develop the Attitude-Scenario-Emotion (ASE) model of sentiments, in which enduring attitudes represent others' social-relational value and moderate discrete emotions across scenarios. Sentiments are functional networks of attitudes and emotions. Distinct sentiments, including love, respect, like, hate, and fear, track distinct relational affordances, and each is emotionally pluripotent, thereby serving both bookkeeping and commitment functions within relationships. The sentiment contempt is an absence of respect; from cues to others' low efficacy, it represents them as worthless and small, muting compassion, guilt, and shame and potentiating anger, disgust, and mirth. This sentiment is ancient yet implicated in the ratcheting evolution of human ultrasocialty. The manifolds of the contempt network, differentially engaged across individuals and populations, explain the features of "contempt," its translatability, and its variable experience as "hot" or "cold," occurrent or enduring, and anger-like or disgust-like. This rapprochement between psychological anthropology and evolutionary psychology contributes both methodological and empirical insights, with broad implications for understanding the functional and cultural organization of social affect. PMID- 27001169 TI - Low Energy Atomic Models Suggesting a Pilus Structure that could Account for Electrical Conductivity of Geobacter sulfurreducens Pili. AB - The metallic-like electrical conductivity of Geobacter sulfurreducens pili has been documented with multiple lines of experimental evidence, but there is only a rudimentary understanding of the structural features which contribute to this novel mode of biological electron transport. In order to determine if it was feasible for the pilin monomers of G. sulfurreducens to assemble into a conductive filament, theoretical energy-minimized models of Geobacter pili were constructed with a previously described approach, in which pilin monomers are assembled using randomized structural parameters and distance constraints. The lowest energy models from a specific group of predicted structures lacked a central channel, in contrast to previously existing pili models. In half of the no-channel models the three N-terminal aromatic residues of the pilin monomer are arranged in a potentially electrically conductive geometry, sufficiently close to account for the experimentally observed metallic like conductivity of the pili that has been attributed to overlapping pi-pi orbitals of aromatic amino acids. These atomic resolution models capable of explaining the observed conductive properties of Geobacter pili are a valuable tool to guide further investigation of the metallic-like conductivity of the pili, their role in biogeochemical cycling, and applications in bioenergy and bioelectronics. PMID- 27001170 TI - Divergent creative thinking in young and older adults: Extending the effects of an episodic specificity induction. AB - Recent research has suggested that an episodic specificity induction-brief training in recollecting the details of a past experience-enhances divergent creative thinking on the alternate uses task (AUT) in young adults, without affecting performance on tasks thought to involve little divergent thinking; however, the generalizability of these results to other populations and tasks is unknown. In the present experiments, we examined whether the effects of an episodic specificity induction would extend to older adults and a different index of divergent thinking, the consequences task. In Experiment 1, the specificity induction significantly enhanced divergent thinking on the AUT in both young and older adults, as compared with a control induction not requiring specific episodic retrieval; performance on a task involving little divergent thinking (generating associates for common objects) did not vary as a function of induction. No overall age-related differences were observed on either task. In Experiment 2, the specificity induction significantly enhanced divergent thinking (in terms of generating consequences of novel scenarios) in young adults, relative to another control induction not requiring episodic retrieval. To examine the types of creative ideas affected by the induction, the participants in both experiments also labeled each of their divergent-thinking responses as an "old idea" from memory or a "new idea" from imagination. New, and to some extent old, ideas were significantly boosted following the specificity induction relative to the control. These experiments provide novel evidence that an episodic specificity induction can boost divergent thinking in young and older adults, and indicate that episodic memory is involved in multiple divergent thinking tasks. PMID- 27001171 TI - Network meta-analysis of efficacy and safety of competitive oral anticoagulants in patients undergoing radiofrequency catheter ablation of atrial fibrillation. AB - PURPOSE: The aim of this network meta-analysis was to evaluate the comparative efficacy and safety of dabigatran, rivaroxaban, apixaban, interrupted vitamin K antagonist (I-VKA), and continuous VKA (C-VKA) in patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify clinical trials comparing dabigatran, rivaroxaban, or apixaban with I-VKA or C-VKA, or against each other, in AF patients undergoing RFCA. A network meta-analysis was conducted to directly and indirectly compare the efficacy and safety of competitive anticoagulation regimens with a Bayesian random-effects model. RESULTS: A total of 39 studies enrolling 27,766 patients were included. C-VKA demonstrated significant superiority over I-VKA in reducing thromboembolic events (risk difference [RD] -0.0068, 95 % confidence interval [CI] -0.0106 to -0.0032) and major bleeding complications (RD -0.0044, 95 % CI 0.0098 to -0.0006). Rivaroxaban compared with I-VKA was associated with a lower risk of thromboembolism (RD -0.0073, 95 % CI -0.0134 to -0.0012), being at the best ranking position among all of the compared anticoagulation regimens in terms of both the efficacy and safety. None of the remaining comparisons reached statistically significant difference in the rate of thromboembolism or major bleeding. CONCLUSIONS: The present study suggests that C-VKA is superior to I-VKA for AF patients undergoing RFCA. Rivaroxaban is the highest probability to be the optimal alternative to C-VKA among the three non-VKA oral anticoagulants in AF ablation. PMID- 27001173 TI - The decline in dental caries among Korean children aged 8 and 12 years from 2000 to 2012 focusing SiC Index and DMFT. AB - BACKGROUND: The aim of this study was to analyse the prevalence and severity of dental caries among Korean children aged 8 and 12 years over a period of 12 years by determining the number of decayed, missing, and filled teeth (DMFT) and the Significant Caries index (SiC index). METHODS: Stratified cluster-sampled data from the National Oral Health Survey conducted from 2000 to 2012 were analysed. In 2000, 2006, and 2012, a total of 2397, 2650, and 9601 children aged 8 and 12 years were examined, respectively. The children's oral health status, including the number of DMFT and fissures sealed teeth, was examined and recorded. The SiC index was calculated according to the child's residential district. RESULTS: Over the 12-year period, the percentages of caries-free children aged 8 and 12 years increased from 26.0 to 42.7 % and from 53.4 to 69.6 %, respectively. The percentages of children aged 8 and 12 years with sealed teeth in 2012 were 62.1 and 62.5 %, respectively, more than triple the rates in 2000. The mean DMFT values of children aged 8 and 12 years decreased from1.04 to 0.67 and from 2.86 to 1.84, respectively. The SiC index of children aged 8 and 12 years also decreased from 2.73 to 1.97 and from 6.13 to 4.51, respectively. The rate of reduction in DMFT among 8- and 12-year-old children in the second 6 years of the observation period was lower than that in the first 6 years. CONCLUSIONS: A remarkable decline in dental caries of 8- and 12-year-old Korean children was observed over the 12-year study period. The mean DMFT values and SiC index of children aged 8 and 12 years decreased. The reduction rate between 2000 and 2006 was higher than that between 2006 and 2012. PMID- 27001172 TI - ITGA6 is directly regulated by hypoxia-inducible factors and enriches for cancer stem cell activity and invasion in metastatic breast cancer models. AB - BACKGROUND: Hypoxia-inducible factors (HIFs) are well-established mediators of tumor growth, the epithelial to mesenchymal transition (EMT) and metastasis. In several types of solid tumors, including breast cancers, the HIFs play a critical role in maintaining cancer stem cell (CSC) activity. Thus, we hypothesized that HIFs may also regulate transcription of markers of breast CSC activity. One approach to enrich for breast cells with stem-like phenotypes is FACS sorting, in which sub-populations of live cells are gated based on the expression of cell surface antigens, including various integrin subunits. Integrin alpha 6 (ITGA6; CD49f) is routinely used in combination with other integrin subunits to enrich for breast stem cells by FACS. Integrins not only mediate interactions with the extracellular matrix (ECM), but also drive intracellular signaling events that communicate from the tumor microenvironment to inside of the tumor cell to alter phenotypes including migration and invasion. METHODS: We used two models of metastatic breast cancer (MBC), polyoma middle T (MMTV-PyMT) and MDA-MB-231 cells, to compare the expression of ITGA6 in wild type and knockout (KO) or knockdown cells. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays verified that ITGA6 is a direct HIF transcriptional target. We also used FACS sorting to enrich for CD49f (+) cells to compare tumorsphere formation, tumor initiating cell activity, invasion and HIF activity relative to CD49f(neg or low) cells. Knockdown of ITGA6 significantly reduced invasion, whereas re expression of ITGA6 in the context of HIF knockdown partially rescued invasion. A search of public databases also revealed that ITGA6 expression is an independent prognostic factor of survival in breast cancer patients. RESULTS: We report that ITGA6 is a HIF-dependent target gene and that high ITGA6 expression enhances invasion and tumor-initiating cell activities in models of MBC. Moreover, cells that express high levels of ITGA6 are enriched for HIF-1alpha expression and the expression of HIF-dependent target genes. CONCLUSIONS: Our data suggest that HIF dependent regulation of ITGA6 is one mechanism by which sorting for CD49f (+) cells enhances CSC and metastatic phenotypes in breast cancers. Our results are particularly relevant to basal-like breast cancers which express higher levels of the HIFalpha subunits, core HIF-dependent target genes and ITGA6 relative to other molecular subtypes. PMID- 27001174 TI - Characterization of cognitive impairments and neurotransmitter changes in a novel transgenic mouse lacking Slc10a4. AB - An orphan member of the solute carrier (SLC) family SLC10, SLC10A4 has been found to be enriched in midbrain and brainstem neurons and has been found to co localize with and to affect dopamine (DA) homeostasis. We generated an SLC10A4 knockout mouse (Slc10a4(Delta/Delta)) using Cre-targeted recombination, and characterized behavioral measures of motor and cognitive function as well as DA and acetylcholine (ACh) levels in midbrain and brainstem. In agreement with previous studies, Slc10a4 mRNA was preferentially expressed in neurons in the brains of wild-type (Slc10a4(+/+)) mice and was enriched in dopaminergic and cholinergic regions. Slc10a4(Delta/Delta) mice had no impairment in motor function or novelty-induced exploratory behaviors but performed significantly worse in measures of spatial memory and cognitive flexibility. Slc10a4(Delta/Delta) mice also did not differ from Slc10a4(+/+) in measures of anxiety. High-performance liquid chromatography (HPLC) measures on tissue punches taken from the dorsal and ventral striatum reveal a decrease in DA content and a corresponding increase in the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), indicating an increase in DA turnover. Punches taken from the brainstem revealed a decrease in ACh as compared with Slc10a4(+/+) littermates. Together, these data indicate that loss of SLC10A4 protein results in neurotransmitter imbalance and cognitive impairment. PMID- 27001175 TI - Direction-dependent activation of the insular cortex during vertical and horizontal hand movements. AB - The planning of any motor action requires a complex multisensory processing by the brain. Gravity - immutable on Earth - has been shown to be a key input to these mechanisms. Seminal fMRI studies performed during visual perception of falling objects and self-motion demonstrated that humans represent the action of gravity in parts of the cortical vestibular system; in particular, the insular cortex and the cerebellum. However, little is known as to whether a specific neural network is engaged when processing non-visual signals relevant to gravity. We asked participants to perform vertical and horizontal hand movements without visual control, while lying in a 3T-MRI scanner. We highlighted brain regions activated in the processing of vertical movements, for which the effects of gravity changed during execution. Precisely, the left insula was activated in vertical movements and not in horizontal movements. Moreover, the network identified by contrasting vertical and horizontal movements overlapped with neural correlates previously associated to the processing of simulated self motion and visual perception of the vertical direction. Interestingly, we found that the insular cortex activity is direction-dependent which suggests that this brain region processes the effects of gravity on the moving limbs through non visual signals. PMID- 27001177 TI - Sex differences in hypothalamic-mediated tonic norepinephrine release for thermal hyperalgesia in rats. AB - Neuropathic pain is treated using serotonin norepinephrine reuptake inhibitors with mixed results. Pain facilitation mediated by alpha1-adrenoceptors may be involved, but whether norepinephrine (NE) is tonically released is unclear. The aim of this study was to determine whether NE is tonically released from A7 cells following chronic constriction injury (CCI), and if the lateral hypothalamus (LH) plays a role in this release in male and female rats with nociceptive and neuropathic pain types. Neuropathic groups received left CCI while nociceptive groups remained naive to injury. Fourteen days later, rats were given intrathecal infusion of either the alpha1-adrenoceptor antagonist WB4101, the alpha2 adrenoceptor antagonist yohimbine (74 MUg), or normal saline for control. Paw withdrawal latency (PWL) from a thermal stimulus was measured. The generalized estimated equation method was used for statistical analysis. Nociceptive rats given WB4101 had a PWL significantly longer than saline control (7.89 +/- 0.63 vs. 5.87 +/- 0.52 s), while the PWL of neuropathic rats given WB4101 was 13.20 +/ 0.52 s compared to 6.78 +/- 0.52 s for the saline control rats. Yohimbine had no significant effect. Microinjection of cobalt chloride (CoCl) in the A7 catecholamine cell group to prevent synaptic transmission blocked the effect of WB4101 in all groups, supporting the notion that spinally descending A7 cells tonically release NE that contributes to alpha1-mediated nociceptive facilitation. Microinjection of CoCl into the left LH blocked the effect of WB4101 in nociceptive and neuropathic male rats, but had no effect in female rats of either pain type, suggesting differential innervation. These findings indicate that tonic release of NE acts at pronociceptive alpha1-adrenoceptors, that this effect is greater in rats with nerve damage, and that, while NE comes primarily from the A7 cell group, LH innervation of the A7 cell group is different between the sexes. PMID- 27001176 TI - Anatomical and functional connections between the locus coeruleus and the nucleus tractus solitarius in neonatal rats. AB - This study was designed to investigate brain connections among chemosensitive areas in newborn rats. Rhodamine beads were injected unilaterally into the locus coeruleus (LC) or into the caudal part of the nucleus tractus solitarius (cNTS) in Sprague-Dawley rat pups (P7-P10). Rhodamine-labeled neurons were patched in brainstem slices to study their electrophysiological responses to hypercapnia and to determine if chemosensitive neurons are communicating between LC and cNTS regions. After 7-10 days, retrograde labeling was observed in numerous areas of the brainstem, including many chemosensitive regions, such as the contralateral LC, cNTS and medullary raphe. Whole-cell patch clamp was done in cNTS. In 4 of 5 retrogradely labeled cNTS neurons that projected to the LC, firing rate increased in response to hypercapnic acidosis (15% CO2), even in synaptic blockade medium (SNB) (high Mg(2+)/low Ca(2+)). In contrast, 2 of 3 retrogradely labeled LC neurons that projected to cNTS had reduced firing rate in response to hypercapnic acidosis, both in the presence and absence of SNB. Extensive anatomical connections among chemosensitive brainstem regions in newborn rats were found and at least for the LC and cNTS, the connections involve some CO2-sensitive neurons. Such anatomical and functional coupling suggests a complex central respiratory control network, such as seen in adult rats, is already largely present in neonatal rats by at least day P7-P10. Since the NTS and the LC play a major role in memory consolidation, our results may also contribute to the understanding of the development of memory consolidation. PMID- 27001178 TI - Visual impairment in FOXG1-mutated individuals and mice. AB - The Forkead Box G1 (FOXG1 in humans, Foxg1 in mice) gene encodes for a DNA binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2 and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1(+/Cre) mice) and of a cohort of subjects carrying FOXG1 mutations or deletions. Visual physiology of Foxg1(+/Cre) mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated individuals with a panel of neuro-ophthalmological assessments, we found that all of them exhibited visual alterations compatible with high-level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and human visual cortical function. PMID- 27001179 TI - Light-emitting diode therapy reduces persistent inflammatory pain: Role of interleukin 10 and antioxidant enzymes. AB - BACKGROUND: During the last decades, the use of light-emitting diode therapy (LEDT) has increased significantly for the treatment of wound healing, analgesia and inflammatory processes. Nevertheless, scientific data on the mechanisms responsible for the therapeutic effect of LEDT are still insufficient. Thus, this study investigated the analgesic, anti-inflammatory and anti-oxidative effect of LEDT in the model of chronic inflammatory hyperalgesia. EXPERIMENTAL PROCEDURES: Mice injected with Complete Freund's Adjuvant (CFA) underwent behavioral, i.e. mechanical and hot hyperalgesia; determination of cytokine levels (tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), IL-10), oxidative stress markers (protein carbonyls and thiobarbituric acid reactive species (TBARS)) and antioxidant enzymes (catalase (CAT) and superoxide dismutase (SOD)). Additionally, mice were pretreated with either naloxone or fucoidin and mechanical hyperalgesia was assessed. RESULTS: LEDT inhibited mechanical and thermal hyperalgesia induced by CFA injection. LEDT did not reduce paw edema, neither influenced the levels of TNF-alpha and IL1-beta; although it increased the levels of IL-10. LEDT significantly prevented TBARS increase in both acute and chronic phases post-CFA injection; whereas protein carbonyl levels were reduced only in the acute phase. LEDT induced an increase in both SOD and CAT activity, with effects observable in the acute but not in the chronic. And finally, pre-administration of naloxone or fucoidin prevented LEDT analgesic effect. CONCLUSIONS: These data contribute to the understanding of the neurobiological mechanisms involved in the therapeutic effect of LEDT as well as provides additional support for its use in the treatment of painful conditions of inflammatory etiology. PMID- 27001180 TI - Characteristics and associated factors of Klee cartilage lesions: preliminary baseline-data of more than 1000 patients from the German cartilage registry (KnorpelRegister DGOU). AB - INTRODUCTION: Knee cartilage lesions are very frequent in arthroscopic surgery. This multi-center-study was aimed to evaluate the distribution and possible associated factors of these pathologies in more than 1000 patients. MATERIALS AND METHODS: The German cartilage registry (KnorpelRegister DGOU) started in 2013. In this paper, we present the baseline-data (distribution of knee cartilage lesions and the demographic data) of more than 1000 cases since the registries' start-up. RESULTS: A total number of 47 centers were involved into this multicenter study. A total of 1071 patients primary were registered. Degenerative knees 629 times (61.8 %) and injured knees 302 times (29.6 %) were involved. In the remaining 89 knees (8.7 %) the genesis of cartilage lesions was unclear. Single defects were observed in 792 cases (77.6 %). Most frequently the medial femoral condyle or the patella was affected. In 78 knees (7.6 %) the main-defect was associated with a defect of the corresponding joint surface. In the remaining cases complex cartilage damages were found. CONCLUSIONS: Our results are in confirmation with other multicenter studies. But these former studies did not differentiate into traumatic and degenerative lesions. Furthermore no characteristics were given regarding to single, kissing or complex lesions. Thus this database will be a sufficient instrument for the investigation of the "natural course" of cartilage lesions, but above all about the effectiveness of different treatment options. PMID- 27001181 TI - A bridging stent to surgery in patients with esophageal and gastroesophageal junction cancer has a dramatic negative impact on patient survival: A retrospective cohort study through data acquired from a prospectively maintained national database. AB - This study aimed to assess the impact of esophageal stenting on postoperative complications and survival in patients with obstructing esophageal and gastroesophageal junction (GEJ) cancer. All patients treated without neoadjuvant therapy that had an R0-resection performed for esophageal and GEJ cancer between January 2003 and December 2010 were identified from a prospectively maintained database. Data on stenting, postoperative mortality, morbidity, recurrence-free survival, complications, and length of hospital stay were collected. Kaplan-Meier plots for survival and recurrence-free survival curves were constructed for R0 resected patients. Data were compared between the stent and no-stent group by nonparametric tests. Two hundred seventy three consecutive R0 resected patients with esophageal or GEJ cancer were identified. Of these patients, 63 had a stent as a bridge to surgery. The male/female ratio was 2.64 (198/75) with a median age in the stent group (SG) of 65.1 versus 64.3 in the no stent group (NSG). Patients were comparable with respect to gender, age, smoking, TNM-classification, oncological treatment, hospital stay, tumor location, and histology. The median survival in the SG was 11.6 months compared with 21.3 months for patients treated without a bridging stent (P < 0.001). There were no statistically significant differences in 30-day mortality between the two groups, but NSG patients exhibited a significantly better two-year survival (P = 0.017). The median recurrence-free survival was 9.1 months for the SG compared with 15.2 months for the NSG. The use of a stent as a bridging procedure to surgery in patients treated without neaoadjuvant therapy for an esophageal or GEJ cancer that later underwent R0 resection decreased the two year survival and the recurrence-free survival. PMID- 27001182 TI - Peak in deaths in 2015 is not a complete mystery. PMID- 27001183 TI - Time Dependent Distribution of MicroRNA 144 after Intravenous Delivery. AB - BACKGROUND: miR-144 has potential benefits in protecting against myocardial ischemia and suppression of tumor growth. We have previously shown that a single intravenous injection of miR-144 provides potent cardioprotection, but its kinetics and distribution are not known. METHODS: Single stranded mature miR-144 or Cy3-labelled-miR-144 was delivered into C57/B6 mice by tail vein injection. RESULTS: After intravenous injection, the signal of Cy3-labelled-miR-144 in the kidney, brain, heart and liver peaks at 60 minutes, and is predominantly localised to the endothelium at that stage. In the kidney and heart, Cy3-labelled miR-144 signal is detectable within the parenchymal tissues for at least 3 days, after which it starts to decrease, but brain Cy3-miR-144 signal rapidly decreases after 1 hour, and is lost at day 1, with no parenchymal uptake detected. Cy3-miR 144 signal can be detected until day 28 in the liver. Stem loop RTPCR confirmed the temporal pattern shown by miR-144 in kidney, brain and heart, but in liver there was a continuous rise following the initial injection until day 28 with no signs of decrease, suggesting de-novo synthesis. CONCLUSION: There is early endothelial uptake of injected miR-144 followed by organ-specific distribution and kinetics. In the liver, there appears to be a positive feedback process that leads to continued accumulation of miR-144 that persists for at least 28 days. These observations should be taken into account when designing experiments utilizing parenteral miR-144 and assessing the biology of its actions. PMID- 27001184 TI - Anti-proliferative Properties of miR-20b and miR-363 from the miR-106a-363 Cluster on Human Carcinoma Cells. AB - BACKGROUND: The miR-106a-363 cluster, encoding six miRNAs (miR- 106a, miR-18b, miR-20b, miR-19b-2, miR-92-2 and miR-363), has been shown to be overexpressed in various tumours. In oral carcinoma cells, however only miR- 106a was detectable from this cluster. We have investigated how effects of transfection of oral carcinoma cells with a non-expressed member of this cluster affect mRNA transcriptomes and cellular selected functions. METHODS: Investigate effects of miR-20b and miR-363 mimics on cellular respiration, glycolysis and mobility. Effects on mRNA transcriptomes were monitored using microarrays. RESULTS: The studies show that in oral carcinoma cells transfected with miR-20b -, or miR-363 3p or miR-363-5p mimic different mRNAs were differentially expressed. Nevertheless, bioinformatics analysis suggested significant associations of differentially expressed genes to inhibition of cellular proliferation, cell cycle and cellular migration. These results were also experimentally confirmed. CONCLUSIONS: Transfection of miRNA mimics for unexpressed members of the miR-106a 363 cluster (miR20b, miR-363-3p and miR-363-5p) exhibit an anti-proliferative effect on oral carcinoma cells, although likely mediated by different regulatory mechanisms. PMID- 27001185 TI - Resistin-Like Molecule-beta Promotes Invasion and Migration of Gastric Carcinoma Cells. AB - BACKGROUND: Resistin-like molecule-beta (RELMbeta) is a novel secretory protein from intestinal goblet cells and participates in epithelial differentiation, tumor occurrence, and immune response. RELMbeta is absent in normal gastric mucosa but is abundantly expressed in gastric carcinoma tissues, and is correlated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) is an important mechanism governing tumor cell invasion. This study thus investigated the modulation of RELMbeta in gastric cancer metastasis and its correlation with EMT. MATERIAL/METHODS: We used RELMbeta-low expression AGS cell line of gastric cancer and normal mucosa cell line GES1 as in vitro models, on which RELMbeta0-expressing vector was transfected. The invasion and migration of cells were quantified by Transwell assay. EMT-related protein including E cadherin, N-cadherin, Snail, and Vimentin were detected by Western blotting in transfected AGS cells. RESULTS: RELMbeta transfection significantly potentiated invasion and migration abilities of AGS cells, whose RELMbeta protein level was significantly elevated compared to those in untransfected AGS or GES1 cells. After RELMb transfection, EMT-related proteins, including N-cadherin, Snail, and Vimentin levels, were elevated, but E-cadherin expression was depressed. CONCLUSIONS: RELMbeta-overexpression can facilitate invasion and migration of gastric carcinoma cells and it increases the expression of EMT-related proteins, such as N-cadherin, Snail, Vimentin, but decreases E-cadherin level, thus promoting the progression of EMT. PMID- 27001186 TI - A phase II clinical trial of fludarabine and cyclophosphamide followed by thalidomide for angioimmunoblastic T-cell lymphoma. An NCRI clinical trial. CRUK number C17050/A5320. PMID- 27001187 TI - Zika virus and neurologic autoimmunity: the putative role of gangliosides. AB - An increasing number of severe neurological complications associated with Zika virus (ZIKV), chiefly Guillain-Barre syndrome (GBS) and primary microcephaly, have led the World Health Organization to declare a global health emergency. Molecular mimicry between glycolipids and surface molecules of infectious agents explain most of the cases of GBS preceded by infection, while a direct toxicity of ZIKV on neural cells has been raised as the main mechanism by which ZIKV induces microcephaly. Gangliosides are crucial in brain development, and their expression correlates with neurogenesis, synaptogenesis, synaptic transmission, and cell proliferation. Targeting the autoimmune response to gangliosides may represent an underexploited opportunity to examine the increased incidence of neurological complications related to ZIKV infection. PMID- 27001188 TI - Chx10 functions as a regulator of molecular pathways controlling the regional identity in the primordial retina. AB - The light-sensitive neural retina (NR) and the retinal pigmented epithelium (RPE) develop from a common primordium, the optic vesicle, raising the question of how they acquire and maintain distinct identities. Here, we demonstrate that sustained misexpression of the Chx10 homeobox gene in the presumptive RPE in chick suppresses accumulation of melanin pigments and promotes ectopic NR-like neural differentiation. This phenotypic change involved ectopic expression of NR transcription factor genes, Sox2, Six3, Rx1 and Optx2, which, when misexpressed, counteracted RPE development without upregulating Chx10. These results suggest that Chx10 can function as a cell autonomous regulator of the regional identity in the primordial retina, presumably through a downstream transcriptional cascade. PMID- 27001189 TI - Waon Therapy for Managing Chronic Heart Failure - Results From a Multicenter Prospective Randomized WAON-CHF Study. AB - BACKGROUND: Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain. METHODS AND RESULTS: In 19 institutes, we prospectively enrolled hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60C for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group. CONCLUSIONS: Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF. PMID- 27001190 TI - Beneficial Effect of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation - Results of the J-RHYTHM Registry 2. AB - BACKGROUND: The J-RHYTHM Registry 2 was a multicenter, prospective observational study that extended the follow-up period of the J-RHYTHM Registry in order to investigate long-term outcomes and effects of non-vitamin K antagonist oral anticoagulants (NOACs) in Japanese patients with atrial fibrillation (AF). METHODS AND RESULTS: Among 6,616 patients with nonvalvular AF (NVAF) (men 71.0%, 69.7+/-9.9 years, CHADS2score 1.7+/-1.2), event rates were compared among patients receiving warfarin (n=3,964), NOACs (n=923), and no anticoagulation therapy (No-OAC, n=753) at the end of follow-up, except for 976 patients lacking anticoagulant data. During the 5-year follow-up period, thromboembolism occurred in 196 (4.9%), 19 (2.1%), and 45 (6.0%) patients, respectively; major hemorrhage in 233 (5.9%), 22 (2.4%), and 36 (4.8%); all-cause death in 230 (5.8%), 13 (1.4%), and 105 (13.9%), (P<0.001 for each). After adjusting for the components of the CHA2DS2-VASc score and antiplatelet drug use, the odds ratio (OR) in the Warfarin group was significantly lower for all-cause death compared with that in the No-OAC group (OR 0.30, 95% confidence interval [CI] 0.23-0.39, P<0.001), whereas ORs in the NOACs group were significantly lower for all events (OR 0.42, 95% CI 0.24-0.74, P=0.003 for thromboembolism; OR 0.53, 95% CI 0.31-0.93, P=0.027 for major hemorrhage; and OR 0.10, 95% CI 0.06-0.18, P<0.001 for all-cause death, respectively). CONCLUSIONS: NOACs could be beneficial for reducing event rates of all types in Japanese NVAF patients. PMID- 27001191 TI - Efficacy and Safety of Inhaled Iloprost in Japanese Patients With Pulmonary Arterial Hypertension - Insights From the IBUKI and AIR Studies. AB - BACKGROUND: Inhaled iloprost is approved for pulmonary arterial hypertension (PAH) in many countries. IBUKI was a phase III, non-randomized, open-label study of the efficacy and safety of inhaled iloprost in Japanese patients with PAH. METHODS AND RESULTS: Adults with PAH who were treatment-naive or administered endothelin receptor antagonists (ERAs) and/or phosphodiesterase type 5 inhibitors (PDE5-Is) and in NYHA/WHO functional class (FC) III/IV had inhaled iloprost (2.5 ug, increased to 5.0 ug if tolerated) 6-9 times daily for 12 weeks. Eligible patients entered a 40-week extension phase. Endpoints included change from baseline to week 12 in pulmonary vascular resistance (PVR; primary endpoint), other efficacy parameters, and safety. Data were compared with new subgroup analyses of treatment-naive Western PAH patients from the global phase III AIR study. 27 patients received iloprost: 89% were treated with an ERA and/or PDE5-I; 70% with both. At week 12, PVR improved from baseline by -124 dyn.sec.cm(-5)(95% CI, -177 to -72) and 6-min walking distance increased by 36.0 m (95% CI, 14.9 to 57.1). NYHA/WHO FC improved in 62%; none worsened. Common drug-related adverse events were headache (37%) and cough (15%); 1 patient experienced hypotension; none reported syncope or hemoptysis. There were no deaths and no unexpected long term safety findings. AIR PAH subgroup analyses showed similar results. CONCLUSIONS: Inhaled iloprost appeared effective and safe in Japanese PAH patients, including ERA- and PDE5-I-treated patients, consistent with findings of the AIR PAH subpopulation and previous iloprost studies. PMID- 27001192 TI - Characteristics and Predictors of Mortality in Patients With Cardiovascular Shock in Japan - Results From the Japanese Circulation Society Cardiovascular Shock Registry. AB - BACKGROUND: There are little data about cardiovascular shock caused by various diseases. We evaluated the characteristics and predictors of 30-day mortality in patients with cardiovascular shock in Japan. METHODS AND RESULTS: The Japanese Circulation Society Cardiovascular Shock registry was a prospective, observational, multicenter, cohort study. Between May 2012 and June 2014, 979 patients with cardiovascular shock were analyzed. The primary endpoint was 30-day all-cause mortality. The mean systolic blood pressure on hospital arrival was 78+/-18 mmHg. The main causes of shock were acute coronary syndrome (51.0%), non ischemic arrhythmia (16.4%), and aortic disease (14.9%). The 30-day all-cause mortality was 34.3%. After adjustment for independent predictors of 30-day mortality, the odds ratios for systolic blood pressure (per 10-mmHg decrease), consciousness disturbance, congestive heart failure, out-of-hospital cardiac arrest, estimated glomerular filtration rate (per 10-ml/min/1.73 m(2)decrease), and causes of shock (non-ischemic arrhythmia, aortic disease, and myocarditis) were 1.15 (95% confidence interval [CI], 1.08-1.22), 2.62 (95% CI, 1.80-3.82), 2.58 (95% CI, 1.67-3.99), 1.62 (95% CI, 1.05-2.51), 1.20 (95% CI, 1.10-1.30), and 0.48 (95% CI, 0.30-0.77), 3.98 (95% CI, 2.32-6.81), and 3.25 (95% CI, 1.20-8.84), respectively. CONCLUSIONS: The 30-day mortality for cardiovascular shock was still high at 34%. Primary predictors of mortality were cardiorenal function on hospital arrival and shock etiology. PMID- 27001193 TI - Henry Krum, PhD 1958-2015. PMID- 27001194 TI - Acne-Like Subcutaneous Phaeohyphomycosis Caused by Cladosporium cladosporioides: A Rare Case Report and Review of Published Literatures. AB - We report a rare case of subcutaneous phaeohyphomycosis caused by Cladosporium cladosporioides. A 21-year-old man was presented to our clinic with the history of cysts and nodules on his face and neck for 5 years. He was diagnosed subcutaneous phaeohyphomycosis according to the finding of fungal elements in histopathological examination and direct microscopic examination of cyst pus, which was confirmed by positive culture of the cyst pus. The isolate grown on culture was identified as C. cladosporioides on the basis of morphological characters and sequence of the ITS region of ribosomal DNA. After treatment with oral itraconazole, he almost completely resolved the inflammatory lesions. To the best of our knowledge, this is the first case report of C. cladosporioides infection presented with multiple cysts and nodules like acne. PMID- 27001196 TI - Pott's puffy tumour: the usefulness of MRI in complicated sinusitis. AB - The sinuses are common sites of infection in children, and if clinical presentation is delayed, there is a high risk of complications including intracranial spread. We present a case of a 5-year-old boy who presented with non specific symptoms of sinusitis. He went on to develop osteomyelitis of the frontal bone and a subperiosteal abscess known as Pott's puffy tumour. Whilst computed tomography provides an excellent initial imaging, this case report emphasizes the advantages of magnetic resonance imaging, especially when there is extensive involvement of the sinuses with an absence of ionizing radiation. Prompt surgical treatment is imperative as there is a potential for significant morbidity if not quickly diagnosed and treated. PMID- 27001195 TI - Improving the utility of MeSH(r) terms using the TopicalMeSH representation. AB - OBJECTIVE: To evaluate whether vector representations encoding latent topic proportions that capture similarities to MeSH terms can improve performance on biomedical document retrieval and classification tasks, compared to using MeSH terms. MATERIALS AND METHODS: We developed the TopicalMeSH representation, which exploits the 'correspondence' between topics generated using latent Dirichlet allocation (LDA) and MeSH terms to create new document representations that combine MeSH terms and latent topic vectors. We used 15 systematic drug review corpora to evaluate performance on information retrieval and classification tasks using this TopicalMeSH representation, compared to using standard encodings that rely on either (1) the original MeSH terms, (2) the text, or (3) their combination. For the document retrieval task, we compared the precision and recall achieved by ranking citations using MeSH and TopicalMeSH representations, respectively. For the classification task, we considered three supervised machine learning approaches, Support Vector Machines (SVMs), logistic regression, and decision trees. We used these to classify documents as relevant or irrelevant using (independently) MeSH, TopicalMeSH, Words (i.e., n-grams extracted from citation titles and abstracts, encoded via bag-of-words representation), a combination of MeSH and Words, and a combination of TopicalMeSH and Words. We also used SVM to compare the classification performance of tf-idf weighted MeSH terms, LDA Topics, a combination of Topics and MeSH, and TopicalMeSH to supervised LDA's classification performance. RESULTS: For the document retrieval task, using the TopicalMeSH representation resulted in higher precision than MeSH in 11 of 15 corpora while achieving the same recall. For the classification task, use of TopicalMeSH features realized a higher F1 score in 14 of 15 corpora when used by SVMs, 12 of 15 corpora using logistic regression, and 12 of 15 corpora using decision trees. TopicalMeSH also had better document classification performance on 12 of 15 corpora when compared to Topics, tf-idf weighted MeSH terms, and a combination of Topics and MeSH using SVMs. Supervised LDA achieved the worst performance in most of the corpora. CONCLUSION: The proposed TopicalMeSH representation (which combines MeSH terms with latent topics) consistently improved performance on document retrieval and classification tasks, compared to using alternative standard representations using MeSH terms alone, as well as, several standard alternative approaches. PMID- 27001197 TI - A high-fat diet combined with food deprivation increases food seeking and the expression of candidate biomarkers of addiction. AB - A mouse model has been developed to study the effect of dietary fat combined with food deprivation periods on palatable food seeking and on the expression of three potential addiction biomarkers in the nucleus accumbens: fumarate hydratase (FH), ATP synthase subunit alpha (ATP5a1) and transketolase (TKT). Forty C57BL/6 J male mice, four-week old, were fed either with a high-fat (HF) diet or standard diet along the experiment. After 3 weeks of differential feeding, animals underwent a two-week training period of two daily sessions where visual cues were paired either to palatable food (chocolate cereals) or no food at all. This training was prolonged one more week with similar, one daily sessions preceded by 12 hours of food deprivation. A behavioural test was finally conducted where mice were confined for 30 minutes either in food unpaired compartments or in compartments previously paired with cereals, but now with empty food trays. Total activity during this behavioural test and serum corticosterone levels right after it were similar in all experimental groups. Mice tested in food-paired compartments showed a marked preference for the empty food tray that gradually disappeared in standard diet-fed individuals but persisted in HF-fed mice. HF-fed mice also overexpressed FH, ATP5a1 and TKT, which positively correlated with the persistence of preference for the empty food tray. It is suggested that HF diets combined with food deprivation may enhance food seeking behaviours while upregulating FH/ATP5a1/TKT, which are further envisaged as biomarkers of addiction. PMID- 27001198 TI - Body composition analysis using abdominal scans from routine clinical care in patients with Crohn's Disease. AB - OBJECTIVE: Crohn's Disease is associated with body composition changes, which have important treatment and prognostic implications. Measurement of body composition usually requires dedicated scanning or measurement, with retrospective analysis of existing datasets impossible. We sought to determine whether single slice analysis of abdominal scans, obtained during routine clinical care, in patients with Crohn's Disease accurately predicts body composition compartments. MATERIALS AND METHODS: Abdominal CT images of patients with Crohn's disease were analyzed and comparison was made with total body fat free mass, total body fat mass, femoral neck t-score, and other parameters reported from DXA, the reference method. RESULTS: Thirty-seven subjects were identified, 15 male and 22 female, with a mean age of 43.8 years. There was significant correlation (Pearson r = 0.923, p < 0.001) between skeletal muscle area from CT and total fat-free mass measured by DXA. Similarly, total body fat mass correlated strongly (r = 0.928, p < 0.0001) with subcutaneous fat area. In this cohort of ambulatory Crohn's Disease patients, low muscle mass/sarcopenia was prevalent and predictive of lower bone mineral density. CONCLUSIONS: Fat mass, fat-free mass, and appendicular skeletal muscle index can be predicted by analysis of a single CT slice in patients with Crohn's Disease. Similar to published data from healthy subjects, the L3 vertebral body level provided the most robust correlation with most parameters. This study represents the first published use of routinely obtained abdominal imaging to demonstrate this relationship - and to predict body composition components - in patients with inflammatory bowel disease. PMID- 27001200 TI - Dying with dignity: a concept analysis. AB - AIMS AND OBJECTIVES: This article is a report of an analysis of the concept of dying with dignity. BACKGROUND: Dignity is an important component of providing care for dying patients and their families. Nevertheless, given that this concept is poorly defined, concept analysis is one of the best ways to define and clarify the concept of death with dignity with the aim to enhance its application in clinical practice, research and education. DESIGN: A search of multiple nursing and social sciences databases was undertaken, including Academic Search Complete, Science Direct, ProQuest, Scopus, Medline, PubMed, EBSCO, Ovid, Noormage, Cinahl, Magiran, PsycINFO and SID. METHODS: After an extensive review of the literature from 1998-2014, about 14 related articles were included in the study. Based on these articles, the applications, attributes and experimental results of and references to death with dignity were recorded. RESULTS: Based on this analysis, the most important attributes of this concept included respect for privacy, respect, spiritual peace and hope. The antecedents of this concept included consideration of moral values during caregiving, preservation of human dignity as a patient right and professional ethics, and belief in the dignity of self and others, consideration of culture in providing end-of-life care. The consequences of this concept included a sense of peace in the patient and their family, peaceful death and provision of patient privacy and comfort. CONCLUSION: The concept of patient dignity has been referred to in many contexts. However, considering the dignity of dying patients commensurate with their culture is the most important component of care provided by nurses to facilitate a peaceful death. RELEVANCE TO CLINICAL PRACTICE: Respecting the dignity of the patient results in the reduction of her/his suffering and prepares her/him for a comfortable death. PMID- 27001201 TI - Shape of the Pulmonary Artery Doppler-Flow Profile Predicts the Hemodynamics of Pulmonary Hypertension Caused by Left-Sided Heart Disease. AB - BACKGROUND: Previous studies demonstrated a relationship between pulmonary hemodynamics and shape of pulmonary artery (PA) Doppler-flow profiles in a mixed pulmonary hypertension (PH) cohort. HYPOTHESIS: Shape of PA Doppler-flow profiles could illustrate the hemodynamic characteristics of pulmonary venous hypertension (PVH), especially identifying it with or without pulmonary vascular disease (PVD). METHODS: We retrospectively analyzed hemodynamic, echocardiographic, and clinical data from 47 patients referred for PH caused by left-sided heart disease (PH-LHD). All patients underwent right-sided heart catheterization within 1 week of echocardiography. We concluded a simple echocardiographic prediction rule to give hemodynamic differentiation of PVH with PVD, defined as capillary wedge pressure >15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units (WU). The PA Doppler-flow profiles were categorized into 2 groups, no notch (NN) and MSN/LSN. RESULTS: The PVR was higher in the MSN/LSN group at 4.04 WU (interquartile range, 3.1-5.3) vs the NN group at 1.91 WU (interquartile range, 1.8-3.0; P < 0.001). Pulmonary artery Doppler-flow notching (MSN and LSN) was highly associated with PVR >3 WU, whereas the NN pattern predicted a PVR <=3 WU (odds ratio: 19.8, 95% confidence interval: 4.3-91.3) and normal transpulmonary pressure gradient <=12 mm Hg (odds ratio: 4.7, 95% confidence interval: 1.3 16.2). The NN pattern had 74% specificity and 88% sensitivity for PVR <=3 WU. CONCLUSIONS: Absence of PA Doppler-flow notching was highly associated with PVH, and a notching pattern indicated PVH with PVD in the PH-LHD cohort. PMID- 27001199 TI - Identification and functional analysis of secreted effectors from phytoparasitic nematodes. AB - BACKGROUND: Plant parasitic nematodes develop an intimate and long-term feeding relationship with their host plants. They induce a multi-nucleate feeding site close to the vascular bundle in the roots of their host plant and remain sessile for the rest of their life. Nematode secretions, produced in the oesophageal glands and secreted through a hollow stylet into the host plant cytoplasm, are believed to play key role in pathogenesis. To combat these persistent pathogens, the identity and functional analysis of secreted effectors can serve as a key to devise durable control measures. In this review, we will recapitulate the knowledge over the identification and functional characterization of secreted nematode effector repertoire from phytoparasitic nematodes. RESEARCH: Despite considerable efforts, the identity of genes encoding nematode secreted proteins has long been severely hampered because of their microscopic size, long generation time and obligate biotrophic nature. The methodologies such as bioinformatics, protein structure modeling, in situ hybridization microscopy, and protein-protein interaction have been used to identify and to attribute functions to the effectors. In addition, RNA interference (RNAi) has been instrumental to decipher the role of the genes encoding secreted effectors necessary for parasitism and genes attributed to normal development. Recent comparative and functional genomic approaches have accelerated the identification of effectors from phytoparasitic nematodes and offers opportunities to control these pathogens. CONCLUSION: Plant parasitic nematodes pose a serious threat to global food security of various economically important crops. There is a wealth of genomic and transcriptomic information available on plant parasitic nematodes and comparative genomics has identified many effectors. Bioengineering crops with dsRNA of phytonematode genes can disrupt the life cycle of parasitic nematodes and therefore holds great promise to develop resistant crops against plant parasitic nematodes. PMID- 27001203 TI - Author's Reply. PMID- 27001202 TI - Coronary Artery Calcium as an Independent Surrogate Marker in the Risk Assessment of Patients With Atrial Fibrillation and an Intermediate Pretest Likelihood for Coronary Artery Disease Admitted to a German Chest Pain Unit. AB - BACKGROUND: About 10% of patients admitted to a chest pain unit (CPU) exhibit atrial fibrillation (AF). HYPOTHESIS: To determine whether calcium scores (CS) are superior over common risk scores for coronary artery disease (CAD) in patients presenting with atypical chest pain, newly diagnosed AF, and intermediate pretest probability for CAD within the CPU. METHODS: In 73 subjects, CS was related to the following risk scores: Global Registry of Acute Coronary Events (GRACE) score, including a new model of a frequency-normalized approach; Thrombolysis In Myocardial Infarction score; European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE); Framingham risk score; and Prospective Cardiovascular Munster Study score. Revascularization rates during index stay were assessed. RESULTS: Median CS was 77 (interquartile range, 1-270), with higher values in men and the left anterior descending artery. Only the modified GRACE (rho = 0.27; P = 0.02) and the SCORE (rho = 0.39; P < 0.005) were significantly correlated with CS, whereas the GRACE (tau = 0.21; P = 0.04) and modified GRACE (tau = 0.23; P = 0.02) scores were significantly correlated with percentile groups. Only the CS significantly discriminated between those with and without stenosis (P < 0.01). CONCLUSIONS: Apart from modified GRACE score, overall correlations between risk scores and calcium burden, as well as revascularization rates during index stay, were low. By contrast, the determination of CS may be used as an additional surrogate marker in risk stratification in AF patients with intermediate pretest likelihood for CAD admitted to a CPU. PMID- 27001204 TI - Tissue fixed with formalin and processed without paraffin embedding is suitable for imaging of both peptides and lipids by MALDI-IMS. AB - Type and quality of sample preparation have significant impact on imaging mass spectrometry results. Though imaging of fresh-frozen tissues is considered to give the best results, they are incompatible with clinical practice, since routine diagnostics is most frequently performed using formalin-fixed tissues, and formalin-fixed paraffin-embedded material is a gold standard in histopathology. We aimed to assess utility of formalin-fixed tissue specimen processed without paraffin embedding (i.e., deep-frozen and cryo-sectioned) for MALDI imaging of both peptides and lipids. Peptide and lipid imaging was performed in fresh-frozen, FFPE and formalin-fixed/frozen samples of a mouse kidney, then composition of the resulting spectra was compared. We demonstrated similarity of spectra registered during peptide imaging in FFPE and formalin fixed/frozen tissues, and similarity of spectra registered during lipid imaging in fresh-frozen and formalin-fixed/frozen material. Furthermore, molecular images of formalin-fixed/frozen tissue resembled the features of both fresh-frozen and FFPE tissue in the case of peptide imaging, and the features of fresh-frozen tissue in the case of lipid imaging. We conclude that tissue preserved by formalin fixation and processed without paraffin embedding can be considered as an alternative to both fresh-frozen and FFPE material. PMID- 27001205 TI - Microwave-antenna induced in situ synthesis of Cu nanowire threaded ZIF-8 with enhanced catalytic activity in H2 production. AB - A microwave-antenna strategy was developed for the in situ synthesis of Cu nanowire (CuNW) threaded ZIF-8. The CuNWs acted as microwave-antennas to generate surface "super hot" dots. The high temperature of "super hot" dots induced adsorption and coordination of metal ions and organic ligands, followed by in situ assembly and crystal-growth along the CuNWs. This catalyst exhibited high activity and stability in H2 production via NH3BH3 hydrolysis owing to the synergetic effect. The CuNWs supplied a rapid electron transfer channel while ZIF 8 assembled on the CuNWs offered a large capacity for adsorbing reactants and channels for rapidly transferring H(-)/H(+) ions toward Cu active sites. Other one-dimensional threaded MOFs, including CuNW threaded MOF-5 and UIO-66, or carbon nanotube threaded ZIF-8 and ZIF-67 could also be prepared using the microwave-antenna strategy. PMID- 27001206 TI - Multi-spectral Metasurface for Different Functional Control of Reflection Waves. AB - Metasurface have recently generated much interest due to its strong manipulation of electromagnetic wave and its easy fabrication compared to bulky metamaterial. Here, we propose the design of a multi-spectral metasurface that can achieve beam deflection and broadband diffusion simultaneously at two different frequency bands. The metasurface is composed of two-layered metallic patterns backed by a metallic ground plane. The top-layer metasurface utilizes the cross-line structures with two different dimensions for producing 0 and pi reflection phase response, while the bottom-layer metasurface is realized by a topological morphing of the I-shaped patterns for creating the gradient phase distribution. The whole metasurface is demonstrated to independently control the reflected waves to realize different functions at two bands when illuminated by a normal linear-polarized wave. Both simulation and experimental results show that the beam deflection is achieved at K-band with broadband diffusion at X-Ku band. PMID- 27001207 TI - Subharmonic instability of a self-organized granular jet. AB - Downhill flows of granular matter colliding in the lowest point of a valley, may induce a self-organized jet. By means of a quasi two-dimensional experiment where fine grained sand flows in a vertically sinusoidally agitated cylinder, we show that the emergent jet, that is, a sheet of ejecta, does not follow the frequency of agitation but reveals subharmonic response. The order of the subharmonics is a complex function of the parameters of driving. PMID- 27001208 TI - Hormone receptor positive, HER2 negative metastatic breast cancer: A systematic review of the current treatment landscape. AB - Endocrine therapy for the treatment of hormone receptor positive, HER2 negative, metastatic breast cancer is continually evolving. We systematically reviewed phase 2 and 3 randomized controlled trials (RCTs) of agents used in this setting to assess the effectiveness and safety of these agents for postmenopausal women. Across the 32 studies in more than 10,000 patients, the greatest improvement in progression-free survival (PFS) was seen with the addition of a cyclin-dependent kinase (CDK)4/6 inhibitor to standard endocrine therapy. Treatment with a mammalian target of rapamycin (mTOR) inhibitor, phosphoinositol-3-kinase (Pi3K) inhibitor, vascular endothelial growth factor (VEGF) inhibitor and with a selective estrogen receptor degrader (SERD) also showed benefit in PFS for selected trials. Overall survival (OS) improved with the use of mTOR inhibitors and a SERD; however, studies were not powered for an OS endpoint. Encouraging results from early studies of histone deacetylase (HDAC) and B-cell lymphoma (BCL2) inhibitors are yet to be confirmed in phase III clinical trials. Study discontinuation rates and toxicity-related deaths were highest with VEGF inhibitors in combination with endocrine therapy, limiting their use in hormone receptor positive breast cancer. CDK4/6 inhibitors and mTOR inhibitors appeared to have activity in both first and second line settings, but required additional monitoring for common toxicities. The activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors was limited to the first-line setting and treatment discontinuation rates were higher than with mTOR inhibitors and SERDs. Overall, PFS benefit appears to be greatest when agents acting on CDK4/6, mTOR and Pi3K pathways, and SERDs are added to standard endocrine therapy. If these early results persist in further studies, these data are likely to change the way we treat hormone receptor positive, HER2 negative metastatic breast cancer. In the follow-up article to this review, we will consider the potential future treatment options for these patients. PMID- 27001209 TI - Hormone receptor positive, HER2 negative metastatic breast cancer: Future treatment landscape. AB - Endocrine therapy is an established and effective treatment strategy for hormone receptor positive metastatic breast cancer. The clinical utility of endocrine therapy is lost over time due to evolving changes in tumor biology and the development of endocrine resistance. Many agents targeting the intracellular signaling pathways associated with endocrine resistance are in development. Encouraging early results have been seen for agents which directly target the estrogen receptor (ER), inhibitors of co-signaling pathways, inhibitors of ER chaperones, ER antagonists able to inhibit mutated or otherwise activated ERs, and modulators of histone acetylation restoring synthesis of ER signaling components. Following our systematic review of treatments with established benefits in this supplement, we review some of the more promising new strategies for overcoming endocrine resistance, looking at the impact on disease control and quality of life for women with hormone receptor positive, HER2 negative breast cancer. We also examine the biomarkers that may guide selection of the best therapy for the individual. PMID- 27001210 TI - A Hydrazone-Based exo-Directing-Group Strategy for beta C-H Oxidation of Aliphatic Amines. AB - Described is a new hydrazone-based exo-directing group (DG) strategy developed for the functionalization of unactivated primary beta C-H bonds of aliphatic amines. Conveniently synthesized from protected primary amines, the hydrazone DGs are shown to site-selectively promote the beta-acetoxylation and tosyloxylation via five-membered exo-palladacycles. Amines with a wide scope of skeletons and functional groups are tolerated. Moreover, the hydrazone DG can be readily removed, and a one-pot C-H acetoxylation/DG removal protocol was also discovered. PMID- 27001211 TI - Anterior cingulum white matter is altered in tobacco smokers. AB - BACKGROUND AND OBJECTIVES: The anterior cingulate cortex (ACC) is hypothesized to be involved in decision making and emotion regulation. Previous observations of drug dependent individuals indicate that substance dependence may be associated with cingulum white matter abnormalities. The present study evaluated cingulum white matter in cigarette smokers. METHODS: Diffusion tensor imaging (DTI) in adult tobacco smokers and healthy non-smoker controls (total N = 70) was performed in a 3T Siemens Trio MRI scanner. RESULTS: Analyses of DTI tractography of the cingulum in tobacco-smoking individuals and controls indicated that tobacco abusers have significantly reduced fractional anisotropy (FA) in the right cingulum. In addition, FA in the left cingulum white matter was negatively associated with the number of cigarettes smoked per day and the Fagerstrom test for nicotine dependence, a self-report measure of tobacco dependence severity. CONCLUSIONS: The white matter of the cingulum is altered in a non-symmetrical way in tobacco smokers. An inverse relationship between FA and reported number of cigarettes per day was observed. Previous studies have also noted altered neural connectivity in cigarette smokers using similar methods. Similar white matter differences in the cingulum have been observed in methamphetamine dependent individuals and patients with dementia, which suggests that the cingulum may be altered by mechanisms not specific to tobacco exposure. SCIENTIFIC SIGNIFICANCE: By better understanding the effects of tobacco abuse on the brain, we hope to gain insight into how drug dependence influences the neurological foundations of behavior. PMID- 27001212 TI - Transcriptome and metabolite profiling reveals that prolonged drought modulates the phenylpropanoid and terpenoid pathway in white grapes (Vitis vinifera L.). AB - BACKGROUND: Secondary metabolism contributes to the adaptation of a plant to its environment. In wine grapes, fruit secondary metabolism largely determines wine quality. Climate change is predicted to exacerbate drought events in several viticultural areas, potentially affecting the wine quality. In red grapes, water deficit modulates flavonoid accumulation, leading to major quantitative and compositional changes in the profile of the anthocyanin pigments; in white grapes, the effect of water deficit on secondary metabolism is still largely unknown. RESULTS: In this study we investigated the impact of water deficit on the secondary metabolism of white grapes using a large scale metabolite and transcript profiling approach in a season characterized by prolonged drought. Irrigated grapevines were compared to non-irrigated grapevines that suffered from water deficit from early stages of berry development to harvest. A large effect of water deficit on fruit secondary metabolism was observed. Increased concentrations of phenylpropanoids, monoterpenes, and tocopherols were detected, while carotenoid and flavonoid accumulations were differentially modulated by water deficit according to the berry developmental stage. The RNA-sequencing analysis carried out on berries collected at three developmental stages-before, at the onset, and at late ripening-indicated that water deficit affected the expression of 4,889 genes. The Gene Ontology category secondary metabolic process was overrepresented within up-regulated genes at all the stages of fruit development considered, and within down-regulated genes before ripening. Eighteen phenylpropanoid, 16 flavonoid, 9 carotenoid, and 16 terpenoid structural genes were modulated by water deficit, indicating the transcriptional regulation of these metabolic pathways in fruit exposed to water deficit. An integrated network and promoter analyses identified a transcriptional regulatory module that encompasses terpenoid genes, transcription factors, and enriched drought responsive elements in the promoter regions of those genes as part of the grapes response to drought. CONCLUSION: Our study reveals that grapevine berries respond to drought by modulating several secondary metabolic pathways, and particularly, by stimulating the production of phenylpropanoids, the carotenoid zeaxanthin, and of volatile organic compounds such as monoterpenes, with potential effects on grape and wine antioxidant potential, composition, and sensory features. PMID- 27001214 TI - Simultaneous detection of xenon and krypton in equine plasma by gas chromatography-tandem mass spectrometry for doping control. AB - Xenon can activate the hypoxia-inducible factors (HIFs). As such, it has been allegedly used in human sports for increasing erythropoiesis. Krypton, another noble gas with reported narcosis effect, can also be expected to be a potential and less expensive erythropoiesis stimulating agent. This has raised concern about the misuse of noble gases as doping agents in equine sports. The aim of the present study is to establish a method for the simultaneous detection of xenon and krypton in equine plasma for the purpose of doping control. Xenon- or krypton fortified equine plasma samples were prepared according to reported protocols. The target noble gases were simultaneously detected by gas chromatography-triple quadrupole mass spectrometry using headspace injection. Three xenon isotopes at m/z 129, 131, and 132, and four krypton isotopes at m/z 82, 83, 84, and 86 were targeted in selected reaction monitoring mode (with the precursor ions and product ions at identical mass settings), allowing unambiguous identification of the target analytes. Limits of detection for xenon and krypton were about 19 pmol/mL and 98 pmol/mL, respectively. Precision for both analytes was less than 15%. The method has good specificity as background analyte signals were not observed in negative equine plasma samples (n = 73). Loss of analytes under different storage temperatures has also been evaluated. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001213 TI - Deficiency of 14-3-3epsilon and 14-3-3zeta by the Wnt1 promoter-driven Cre recombinase results in pigmentation defects. AB - BACKGROUND: The seven 14-3-3 protein isoforms bind to numerous proteins and are involved in a wide variety of cellular events, including the cell cycle, cell division, apoptosis and cancer. We previously found the importance of 14-3-3 proteins in neuronal migration of pyramidal neurons in the developing cortex. Here, we test the function of 14-3-3 proteins in the development of neural crest cells in vivo using mouse genetic approaches. RESULTS: We found that 14-3-3 proteins are important for the development of neural crest cells, in particular for the pigmentation of the fur on the ventral region of mice. CONCLUSIONS: Our data obtained from the 14-3-3epsilon/14-3-3zeta/Wnt1-Cre mice strongly indicate the importance of 14-3-3 proteins in the development of melanocyte lineages. PMID- 27001215 TI - PSCA rs2294008 polymorphism contributes to the decreased risk for cervical cancer in a Chinese population. AB - Recently, three genome-wide association studies have identified the PSCA (prostate stem cell antigen) rs2294008 polymorphism (C > T) associated with susceptibility to gastric cancer, bladder cancer, and duodenal ulcers, highlighting its critical role in disease pathogenesis. Given PSCA is reported to be overexpressed in cervical cancer and the rs2294008 can influence PSCA transcription, we aimed to determine the role of rs2294008 in susceptibility to cervical cancer. The genotyping was performed in the 1126 cases and 1237 controls. Our results showed the rs2294008 TT genotype significantly associated with a reduced risk of cervical cancer (adjusted OR = 0.55, 95% CI = 0.38-0.79; recessive model). Stratified analyses revealed that the association was restricted to the subgroups of age > 49 years, parity <= 1, abortion and early stage cervical cancer. Immunohistochemistry assay showed the individuals carrying the TT genotype having lower PSCA expression than those with CC/CT genotypes. In summary, the PSCA rs2294008 polymorphism may serve as a biomarker of cervical cancer, particularly of early-stage cervical cancer. PMID- 27001216 TI - A Fiber Supercapacitor with High Energy Density Based on Hollow Graphene/Conducting Polymer Fiber Electrode. AB - A hollow graphene/conducting polymer composite fiber is created with high mechanical and electronic properties and used to fabricate novel fiber-shaped supercapacitors that display high energy densities and long life stability. The fiber supercapacitors can be woven into flexible powering textiles that are particularly promising for portable and wearable electronic devices. PMID- 27001217 TI - Preoperative voiding dysfunction is a risk factor for operative failure according to the VALUE study! PMID- 27001218 TI - Decorin over-expression by decidual cells in preeclampsia: a potential blood biomarker. AB - BACKGROUND: Decorin, a leucine-rich proteoglycan that is produced by decidual cells, limits invasion and endovascular differentiation of extravillous trophoblast cells during early placentation by binding to multiple tyrosine kinase receptors, in particular, vascular endothelial growth factor receptor-2. OBJECTIVE: Because many studies have reported an association between poor trophoblast invasion and endovascular differentiation with preeclampsia, the studies reported here tested (1) whether decorin over-expression in the chorionic villi and/or basal decidua is associated with preeclampsia and, if so, (2) whether this association results in a hypoinvasive placenta, and (3) whether elevated plasma decorin concentration in the second trimester is a predictive biomarker for preeclampsia. STUDY DESIGN: Decorin messenger RNA expression was measured with quantitative polymerase chain reaction at the tissue level and with in situ hybridization at the cellular level using (35)S-labeled antisense complimentary RNA probe in placentas from healthy control subjects and subjects with preeclampsia (14 each, 23-40 weeks of gestation). Tissue sections of the same placentas were also immunostained for decorin protein. A decorin over expressing human endometrial stromal cell line was tested for invasion-regulatory effects on an invasive first-trimester extravillous trophoblast cell line HTR 8/SVneo plated in cocultures that were separated by a semipermeable membrane. Furthermore, we conducted retrospective measurements of plasma decorin levels during the second trimester (15-18 weeks of gestation) in a cohort of 28 body mass index-matched pairs of control subjects and subjects with preeclampsia before the onset of clinical disease. RESULTS: First, decorin messenger RNA expression at the cellular level measured with in situ hybridization exhibited profoundly higher expression levels in basal plate decidual cells within the placentas from preeclamptic subjects than those from control subjects at all gestational ages, whereas no difference between the 2 subject groups was noted in villus mesenchymal cells. Similarly decorin messenger RNA expression at the tissue level in chorionic villi (primarily resulting from fetally derived mesenchymal cells) did not differ significantly between control and preeclampsia placentas. These findings were validated with immunostaining for decorin protein. Second, knocking down decorin gene in a decorin over-expressing endometrial cell line (used as an in vitro surrogate of decorin over-expressing decidual cells) in cocultures with extravillous trophoblast cells abrogated its invasion-restraining actions on trophoblast cells, which indicated paracrine contribution of decorin over-expressing decidua to the poor trophoblast invasiveness in situ. Finally, retrospective measurement of plasma decorin levels during the second trimester in 28 body mass index-matched pairs of control subjects and subjects with preeclampsia revealed elevated plasma decorin levels in all subjects with preeclampsia in all body mass index groups. A receiver operating characteristic curve analysis revealed strong diagnostic performance of plasma decorin in the prediction of preeclampsia status. Although there was no significant gestational age-related change in decorin levels during the second trimester in control or subjects with preeclampsia, we found that plasma decorin had a significant inverse relationship with body mass index or bodyweight. CONCLUSION: We conclude that decorin over-expression by basal decidual cells is associated with hypoinvasive phenotype and poor endovascular differentiation of trophoblast cells in preeclampsia and that elevated plasma decorin concentration is a potential predictive biomarker for preeclampsia before the onset of clinical signs. PMID- 27001219 TI - Textile properties of synthetic prolapse mesh in response to uniaxial loading. AB - BACKGROUND: Although synthetic mesh is associated with superior anatomic outcomes for the repair of pelvic organ prolapse, the benefits of mesh have been questioned because of the relatively high complication rates. To date, the mechanisms that result in such complications are poorly understood, yet the textile characteristics of mesh products are believed to play an important role. Interestingly, the pore diameter of synthetic mesh has been shown to impact the host response after hernia repair greatly, and such findings have served as design criteria for prolapse meshes, with larger pores viewed as more favorable. Although pore size and porosity are well-characterized before implantation, the changes in these textile properties after implantation are unclear; the application of mechanical forces has the potential to greatly alter pore geometries in vivo. Understanding the impact of mechanical loading on the textile properties of mesh is essential for the development of more effective devices for prolapse repair. OBJECTIVE: The objective of this study was to determine the effect of tensile loading and pore orientation on mesh porosity and pore dimensions. STUDY DESIGN: In this study, the porosity and pore diameter of 4 currently available prolapse meshes were examined in response to uniaxial tensile loads of 0.1, 5, and 10 N while mimicking clinical loading conditions. The textile properties were compared with those observed for the unloaded mesh. Meshes included Gynemesh PS (Ethicon, Somerville, NJ), UltraPro (Artisyn; Ethicon), Restorelle (Coloplast, Minneapolis, MN), and Alyte Y-mesh (Bard, Covington, GA). In addition to the various pore geometries, 3 orientations of Restorelle (0-, 5-, 45-degree offset) and 2 orientations of UltraPro (0-, 90 degree offset) were examined. RESULTS: In response to uniaxial loading, both porosity and pore diameter dramatically decreased for most mesh products. The application of 5 N led to reductions in porosity for nearly all groups, with values decreasing by as much as 87% (P < .05). On loading to 10 N of force, nearly all mesh products that were tested were found to have porosities that approached 0% and 0 pores with diameters >1 mm. CONCLUSION: In this study, it was shown that the pore size of current prolapse meshes dramatically decreases in response to mechanical loading. These findings suggest that prolapse meshes, which are more likely to experience tensile forces in vivo relative to hernia repair meshes, have pores that are unfavorable for tissue integration after surgical tensioning and/or loading in urogynecologic surgeries. Such decreases in pore geometry support the hypothesis that regional increases in the concentration of mesh leads to an enhanced local foreign body response. Although pore deformation in transvaginal meshes requires further characterization, the findings presented here provide a mechanical understanding that can be used to recognize potential areas of concern for complex mesh geometries. Understanding mesh mechanics in response to surgical and in vivo loading conditions may provide improved design criteria for mesh and a refinement of surgical techniques, ultimately leading to better patient outcomes. PMID- 27001220 TI - Excision of an epidermal inclusion cyst: Correction of a long-term complication of female genital circumcision. AB - Epidermal inclusion cysts are a late complication of female genital circumcision, which is a practice that affects 125 million women primarily from Africa and the Middle East. A 30-year-old woman, gravida 4, para 1, presented to our clinic with an 8-year history of a slowly enlarging periclitoral mass. The patient had undergone female genital circumcision at the age of 5 years. We describe and video-illustrate the surgical technique of excising the 8-cm epidermal inclusion cyst. Using this technique, the entire cyst was resected intact, excess vulvar skin removed, and defect repaired. Postoperatively, she had minimal pain, no dyspareunia, and good cosmesis. Restoration of anatomy for this late complication of female genital circumcision is achievable with knowledge of anatomy, adherence to basic surgical principles that include tension-free closure, and close postoperative follow up. PMID- 27001221 TI - Rates of human papillomavirus vaccine uptake amongst girls five years after introduction of statewide mandate in Virginia. AB - BACKGROUND: The Commonwealth of Virginia enacted statewide school-entry human papillomavirus vaccine mandate in 2008 requiring all girls to receive the vaccine before starting the 6th grade. The mandate, one of very few in the country, has been in effect for 5 years. This study assesses the impact that it has had on the rates of human papillomavirus uptake. OBJECTIVE: The purpose of this study was to evaluate the uptake of the human papillomavirus vaccine among girls seeking well child care 5 years after the introduction of a statewide mandate in Virginia in October 2008. STUDY DESIGN: This prospective cohort study used the Clinical Data Repository at the University of Virginia to identify girls 11-12 years old who was seen for well-child care from January to December 2014. Billing and diagnosis codes were used to establish human papillomavirus vaccine administration. Those girls who were identified through the Clinical Data Repository were then contacted by advance letter followed by a representative from the University of Virginia Center for Survey Research who invited the responsible parent or guardian to complete a 50-item telephone questionnaire. Questionnaire results were used to inform objective findings and to assess parental attitudes that were related to human papillomavirus vaccination. Findings were compared against those of Pierce et al (2013), who evaluated human papillomavirus vaccination levels in a similar cohort of patients in 2008, before mandate enactment, to assess relative change attributable to vaccine mandate. RESULTS: Nine hundred eight girls were identified through the Clinical Data Repository; 50.9% of the girls received at least 1 dose of human papillomavirus vaccine. White race and private insurance coverage were found to be associated negatively with human papillomavirus vaccine uptake (relative risk, 0.74 and 0.71; 95% confidence interval, 0.64-0.85 and 0.62-0.81, respectively). Black race and public insurance coverage were found to be associated positively with vaccine uptake (relative risk, 1.35 and 1.39; 95% confidence interval, 1.17-1.55 and 1.22-1.58, respectively). In comparison with the previous study, there has been no change in human papillomavirus vaccine uptake or distribution of uptake after the introduction of the statewide mandate for human papillomavirus vaccination. CONCLUSION: The statewide human papillomavirus vaccine mandate has had no impact on the overall rate of human papillomavirus vaccination, nor has it diminished the previously described racial or payer disparities in vaccine uptake in school aged girls being seen for well-child care in the state of Virginia. PMID- 27001222 TI - Reply. PMID- 27001223 TI - Early failure with the Journey-Deuce bicompartmental knee arthroplasty. AB - The aim of this study was to evaluate the early functional outcome and survivorship of a bicompartmental knee arthroplasty implant (Journey-Deuce) in a cohort of patients with combined medial and patellofemoral degenerative osteoarthritis. Fifteen patients with a mean age of 57 years were followed up prospectively and evaluated with clinical examination, Oxford knee score and radiology imaging. Poor pain scores, concerns about the tibial fixation, early aseptic loosening of the tibial component and a revision rate of 60 % at a minimum follow-up of 54 months are reported. Implantation of this prosthesis was stopped at our institution well before the first revision due to an unfavourable early clinical response. This was further endorsed by an unacceptable revision rate. The outcome of the Journey-Deuce bicompartmental knee replacement was considerably worse than the published outcome of total knee replacement. PMID- 27001224 TI - Relationship between the different torsion-related thoracic deformity parameters of adolescent idiopathic scoliosis. AB - INTRODUCTION: Torsion has recently become essential in curve evaluation, not only to assess the degree of clinical deformity that can influence decision making, but also to predict curve progression. Since torsion cannot be currently measured using plain X-rays, our aim was to study the relationships between the different torsion-related parameters measured on 2D radiographs that can indirectly guide the clinician about the torsion of a given curve. METHODS: This is a cross sectional study analyzing prospectively registered data of a consecutive cohort of 113 AIS patients with progressive main thoracic deformity. Demographic data, the Adams test and eight radiographic torsion-related coronal and sagittal deformity parameters [apical vertebral rotation (AVR)-Stokes method, Mehta angle (RVAD), main thoracic Cobb side-bending, T5-T12 kyphosis, T5-T8 kyphosis, T9-T12 kyphosis, kyphotic change and double rib contour sign (rib index)] were correlated between each other and with the main thoracic Cobb angle (MTCobb). Univariate linear regression and multiple linear stepwise regression analyses were performed as well. RESULTS: The radiographically measurable deformity parameters that best correlated with the MTCobb angle in idiopathic curves were: side-bending, RVAD, AVR and the Adams test. Sagittal variables were correlated the least with MTCobb. Coronal parameters as AVR, RVAD, side-bending and Adam test are highly intercorrelated. Sagittal variables are related between each other but are not directly related to coronal parameters. CONCLUSIONS: There is a strong relationship between the Cobb angle, curve bending, the Mehta angle and the apical vertebral rotation. Together with the clinical Adams test, these are the most important radiographic torsion-related parameters to measure when assessing scoliosis in 2D. LEVEL OF EVIDENCE: 3. PMID- 27001225 TI - Bioresorbable vascular scaffolds: Biodegradation, drug delivery and vascular remodeling. AB - The metallic stents with durable polymers have been effective in reducing the need for revascularization, but the permanent presence of the metal and polymer have been associated with persistent inflammation, hypersensitivity reactions and incidence of thrombosis. Recent innovations of bioresorbable polymers are in development which could serve as temporary scaffolds that degrade into molecules and eventually resorb overtime, and leave the artery free of any permanent prosthetic constraints. The transient scaffolding has the advantages of restoring blood vessel to natural state, improve vasomotor tone and increase lumen enlargement because of expansive remodeling following completion of polymer resorption. The success of bioresorbable vascular scaffolds will depend on the degradation timeline, such that the elastic recoil of the blood vessel and negative remodeling which could potentially lead to restenosis are prevented. Bioresorbable scaffolds with bulky backbone and thick struts could lead to prolonged biodegradation, alter blood flow dynamics and increase thrombogenicity. The development of bioresorbable scaffolds is challenging because of the complexity of finding an ideal balance of polymer biodegradation and controlled drug release over time, such that the fractional drug released achieves optimal inhibitory concentration until the blood vessel remodels to a stable set point. This review discusses the various types of biodegradable materials, factors affecting biodegradation, drug release kinetics, vascular biocompatibility, adaptive vascular remodeling, and challenges in the development of bioresorbable scaffolds to treat vascular restenosis. PMID- 27001226 TI - The pharmacological management of psychiatric comorbidities in patients with epilepsy. AB - Psychiatric disorders represent a frequent comorbidity in patients with epilepsy affecting quality of life, morbidity and mortality. Evidence-based data on the management of these conditions are limited but a number of recommendations are now available to guide clinical practice. The present paper reviews the pharmacological treatment of psychiatric problems in epilepsy with special attention to data coming from randomised controlled trials (RCTs), pharmacological interactions with AEDs and the issue of seizure worsening during treatment with psychotropic drugs. Epidemiologically or clinically relevant psychiatric conditions are discussed namely mood and anxiety disorders, psychoses and attention deficit hyperactivity disorder. PMID- 27001227 TI - Regenerative pharmacology for the treatment of acute kidney injury: Skeletal muscle stem/progenitor cells for renal regeneration? AB - Regenerative pharmacology and advanced therapy medicinal products is a relatively new and challenging field in drug development. Acute kidney injury (AKI) is a common clinical condition in nephrology with increasing incidence and high mortality rate. During the last few decades, researchers have been eagerly trying to find novel therapeutic strategies for AKI treatment, including advanced pharmacological therapies using mesenchymal stem cells (MSCs). Several types of MSCs have been thoroughly investigated, including bone marrow, adipose derived and umbilical cord blood MSCs and shown promising results in kidney repair. Research has demonstrated, that MSCs exert their effect through reduction of apoptosis, increased production of growth factors, suppression of oxidative stress and inflammatory processes, promotion of renal tubular cell proliferation, as well as by migration and direct incorporation into the renal tissue. Skeletal muscle-derived stem/progenitor cells (MDSPCs) are mesenchymal stem cell lineage of multipotent cells, demonstrating long-term proliferation, high self-renewal capacities, and ability to enhance endogenous tissue repair. The capacity of MDSPCs to regenerate a variety of different tissues following acute injury or destructive tissue diseases have been demonstrated in preclinical and clinical studies. MDSPCs were also reported to promote endogenous tissue repair via paracrine pathway. Considering advantageous properties of MDSPCs, the administration of these cells might be considered as a potential strategy for the treatment of AKI. However, to date, the therapeutic effect of MDSPCs for renal regeneration has not been investigated. This review reflects the current development in AKI treatment using different types of MSCs and the pilot results of the experimental study in vivo using a novel type of stem cells - MDSPCs for the treatment of gentamicin-induced AKI. PMID- 27001228 TI - The Caudate Lobe: The Blind Spot in Radioembolization or an Overlooked Opportunity? AB - PURPOSE: The caudate lobe (CL) is impartial to the functional left and right hemi liver and has outspoken inter-individual differences in arterial vascularization. Unfortunately, this complexity is not specifically taken into account during radioembolization treatment (RE), potentially resulting in under- or overtreatment of the CL. The objective of this study was to evaluate the CL coverage in RE and determine the detection rate of the CL arteries on CT angiography during work-up. METHODS: In all consecutive patients who underwent RE treatment between May 2012-January 2015, (99m)Tc-MAA SPECT/CT and posttreatment scans ((90)Y-bremsstrahlung SPECT/CT, (90)Y-PET/CT, or (166)Ho-SPECT/CT) were reviewed for activity in the CL. Pretreatment CT angiographies were reviewed for the visibility of the CL arteries. RESULTS: Eighty-two patients were treated. In 32/82 (39 %) the CL was involved. In 6/32 (19 %) patients, no activity was seen on the posttreatment scan in the CL, whereas in 40/50 (80 %) patients without CL tumor involvement, the CL was treated. (99m)Tc-MAA SPECT/CT and final posttreatment scans were discordant in 16/78 (21 %). (99m)Tc-MAA SPECT/CT had a positive and negative predictive value of 94 % and 46 %, respectively, for activity in the CL after RE. In untreated CLs, significant hypertrophy was observed with a median volume increase of 33 % (p = 0.02). CL arteries were seldom visible on the pretreatment CT; the identification rate was 12-17 %. CONCLUSION: Currently in RE treatments, targeting or sparing of the CL is highly erratic and independent of tumor involvement. Intentional treatment or bypassing of the CL seems worthwhile to either improve tumor coverage or enhance the functional liver remnant. PMID- 27001229 TI - Letter to the Editor Regarding the Article 'Ultrasound-Guided Percutaneous Nephrostomy Performed on Neonates and Infants Using a "14-4" (Trocar and Cannula) Technique'. PMID- 27001230 TI - Differential expression of GAS5 in rapamycin-induced reversion of glucocorticoid resistance. AB - This study evaluates the association between the long noncoding RNA GAS5 levels and the anti-proliferative effect of the glucocorticoid (GC) methylprednisolone (MP) alone and in combination with rapamycin in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. The effect of MP, rapamycin, and MP plus rapamycin was determined in 17 healthy donors by labelling metabolically active cells with [methyl-3H] thymidine and the expression levels of GAS5 gene were evaluated by real-time RT-PCR TaqMan analysis. We confirmed a role for GAS5 in modulating GC response: poor responders presented higher levels of GAS5 in comparison with good responders. Interestingly, when PBMCs were treated with the combination of rapamycin plus MP, the high levels of GAS5 observed for each drug in the MP poor responders group decreased in comparison with rapamycin (P value = 0.0134) or MP alone (P value = 0.0193). GAS5 is involved in GC resistance and co treatment of rapamycin with GCs restores GC effectiveness in poor responders through the downregulation of the long noncoding RNA. GAS5 could be considered a biomarker to personalize therapy and a novel therapeutic target useful for the development of new pharmacological approaches to restore GC sensitivity. PMID- 27001231 TI - Expression and function of transient receptor potential channels in the female bovine reproductive tract. AB - The epithelium lining the oviduct is critical for early reproductive events, many of which are mediated via intracellular calcium ions. Despite this, little is known about the regulation of calcium homeostasis in the oviductal epithelium. Epithelial transient receptor potential channels (TRPCs) modulate calcium flux in other tissues, and their expression and functional regulation have therefore been examined using the bovine oviduct as a model for the human. The effects of FSH, LH, 17beta-estradiol, and progesterone on TRPCs expression and intracellular calcium flux were determined. Transient receptor potential channels 1, 2, 3, 4, and 6 were expressed in the bovine reproductive tract, and their gene expression varied throughout the estrous cycle. In more detailed studies undertaken on TRPC1 and 6, we show that protein expression varied through the estrus cycle; specifically, 17beta-estradiol, FSH, and LH individually and in combination upregulated TRPC1 and 6 expression in cultured bovine oviduct epithelial cells although progesterone antagonized these effects. Functional studies showed changes in calcium mobilization in bovine oviduct epithelial cells were dependent on TRPCs. In conclusion, TRPC1, 2, 3, 4, and 6 are present in the epithelium lining the bovine oviduct, and TRPC1 and 6 vary through the estrous cycle suggesting an important role in early reproductive function. PMID- 27001232 TI - Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters. AB - We screened small-molecule compounds that inhibit osteoclast differentiation to find new anti-osteoporosis agents and found that a novel compound, SUKU-1, suppressed osteoclastogenesis. We also synthesized 38 derivatives of SUKU-1 and discovered that nine of them had inhibitory effects on osteoclastogenesis and that SUKU-33 was the most potent inhibitor. Next, we investigated the mechanisms by which SUKU-33 suppressed osteoclast differentiation. By measuring the uptake of [(3) H]-uridine in cells, we found that SUKU-33 suppressed both equilibrative nucleoside transporters and concentrative nucleoside transporters. These results suggest that SUKU-33 inhibits osteoclast differentiation by suppressing nucleoside transporters. PMID- 27001233 TI - Safety surveillance in haemophilia and allied disorders. AB - The introduction of clotting factor concentrates has transformed the lives of persons with inherited bleeding disorders. With the use of prophylactic treatment, it is now possible to prevent bleeding in these individuals. The early concentrates were contaminated with the HIV and hepatitis C viruses (HCV) and resulted in major morbidity and mortality in the recipients. Current products are much safer, especially in terms of infectious agents, but other adverse events such as alloantibodies (inhibitors), allergic reactions and thrombotic risks remain of concern. Approximately 30% of previously untreated patients with severe haemophilia A develop inhibitors, making this the most important issue in haemophilia care today. Recently, it was suggested that one of the most commonly used concentrates was associated with a higher inhibitor risk, but this was not supported by the evidence from all studies. Good safety surveillance systems are essential for all diseases and products but are particularly so in the group of individuals with inherited bleeding disorders treated with clotting factor concentrates who have suffered disproportionately from the adverse effects of their treatment. National and multinational systems are now in place to allow reporting of adverse events in patients with inherited bleeding disorders. All clinicians treating individuals with inherited bleeding disorders should prospectively report adverse events to treatment even if they are believed to be common and well recognized. PMID- 27001234 TI - Evidence-Based Clinical Practice Guidelines in Neurosurgery. PMID- 27001235 TI - Traumatic Lumbar Subdural Hematoma in the Absence of Intracranial Disease. AB - BACKGROUND: Traumatic spinal subdural hematoma is an exceedingly rare condition, with those occurring in the absence of intracranial disease being particularly uncommon. Only 13 such cases have been reported. Although theories exist to describe the pathophysiology of traumatic spinal subdural hematoma, the precise mechanism and guidelines for management remain unclear. CASE DESCRIPTION: This report describes a 37-year-old woman who suffered a traumatic assault who developed progressive low back pain with radicular symptoms 2 days after presentation. Magnetic resonance imaging revealed a lumbar subdural hematoma extending from L1 to L5. No intracranial disease was detected on imaging. CONCLUSIONS: Definitive guidelines for management of this condition are uncertain; however, successful use of conservative management, lumbar drainage, and surgical evacuation has been reported. This patient underwent a lumbar laminectomy with evacuation of the hematoma, resulting in immediate pain relief and resolution of symptoms within 1 week of the procedure. PMID- 27001236 TI - Ipsilateral Dural Thickening and Enhancement: A Sign of Isolated Cortical Vein Thrombosis? A Case Report and Review of the Literature. AB - BACKGROUND: Isolated cortical vein thrombosis (ICVT) being a rare condition (6% of intracranial vein thromboses), no clinical guidelines and few radiologic clues to it have been established. ICVT mostly appears in conjunction with sinus vein thromboses. ICVTs primarily occur during pregnancy and puerperium (35%). The great variability of cortical veins and difficulty identifying small occluded vessels complicate ICVT diagnosis. We present the first case of isolated ipsilateral dural thickening and enhancement as a potential radiologic sign of ICVT shown on magnetic resonance imaging. CASE DESCRIPTION: A 30-year-old woman presented with sudden position-independent severe headache and neck pain 2 weeks postpartum. Standard magnetic resonance imaging revealed ipsilateral dural thickening and enhancement of the meninges (left hemisphere). The symptoms and findings were interpreted as a post-lumbar puncture syndrome associated with the epidural anesthesia during labor and birth. Deteriorating, the patient was referred to our hospital after a computed tomography scan had revealed atypical left parietal intracranial hemorrhage. Digital cerebral subtraction angiography confirmed a left parietal ICVT as the underlying disease. When systemic anticoagulation was initiated, the patient's condition further deteriorated. Progressive aphasia and right-sided face and arm weakness and numbness developed as a result of increased intracranial hemorrhage volume. We therefore performed craniotomy and hematoma evacuation, after which the patient fully recovered. CONCLUSIONS: We hypothesize that ipsilateral dural thickening and enhancement in patients presenting with severe headache may indicate ICVT and we suggest further diagnostic workup, using venographic study such as computed tomographic venography or magnetic resonance venography. In an inconclusive venographic study with high clinical suspicion for ICVT, catheter cerebral angiography is indicated. PMID- 27001237 TI - Reply to Underlying Mechanism of Trigeminal Neuralgia: Central, Peripheral, or Both? PMID- 27001238 TI - Patterns and Time Dependence of Unspecific Enhancement in Postoperative Magnetic Resonance Imaging After Glioblastoma Resection. AB - OBJECTIVE: Postoperative magnetic resonance imaging (MRI) is recommended soon after glioma surgery to avoid reactive nonneoplastic contrast enhancement indistinguishable from tumor. The purpose of this study was to analyze these patterns of postoperative contrast enhancement at 3 T to define the optimal time frame for postoperative MRI. METHODS: MRI for 206 glioblastoma surgeries in 173 patients who underwent pre- and postoperative and at least 1 follow-up 3T MRI for each surgery were analyzed retrospectively. Postoperative MRI was assessed in consensus by 2 neuroradiologists, blinded to the time after surgery. Postoperative contrast enhancement marginal to the resection cavity was analyzed and classified as vascular, linear, or nodular. The cause of the contrast enhancement (ie, reactive vs. tumor) was assessed by comparing pre-, postoperative, and follow-up MRI. RESULTS: Within 45 hours after surgery, reactive enhancement appeared in 17.9% of cases. After 45 hours, the fraction of reactive changes increased to 34.1%. Linear enhancement was more often reactive (66.1%, 39/59 cases), whereas nodular enhancement was mainly residual tumor (93.2%, 68/73 cases). Specificity of nodular enhancement was high for tumor recurrence/tumor progression (91.5%). CONCLUSIONS: To avoid an increasing number of MRIs with reactive contrast enhancement, postoperative MRI at 3 T should be performed within 45 hours after surgery. However, reactive contrast enhancement can occur at all time points. In these cases, the pattern of the contrast enhancement may help to differentiate its cause. PMID- 27001239 TI - Optimizing the Volume of the Initial Framing Coil to Facilitate Tight Packing of Intracranial Aneurysms. AB - BACKGROUND: During endovascular treatment of an aneurysm, the importance of the initial coil volume for facilitating tight packing is unclear. We retrospectively studied the relationships between initial packing density (PD; initial coil volume divided by aneurysm volume), final PD (volume of all coils divided by aneurysm volume). METHODS: We reviewed 105 aneurysms in 98 patients who underwent endovascular coiling between April 2011 and March 2014. The initial coil was defined as the first coil in the single-catheter method and the first 2 coils in the double-catheter method. The patient data were divided into groups with or without a final PD >=20%, and the significant predictors of a final PD >=20% were determined using multivariable logistic regression. The optimal cutoff value for the initial PD was determined using a receiver operating characteristic curve. RESULTS: Of 105 aneurysms, 56 and 49 were treated with single- and double catheter methods, respectively. Statistically significant differences in rupture status, neck size, dome/neck ratio, and initial PD were observed between aneurysms with and without a final PD >=20% (all P < 0.05). Multivariate analysis showed that initial PD (P = 0.025; odds ratio, 1.22) and rupture status (P = 0.002; odds ratio, 0.19) were significantly associated with a final PD >=20%. Using receiver operating characteristic curve analysis, the cutoff points of initial PD to achieve a final PD >=20% were 8.0% and 10.0% in single- and double catheter groups, respectively. CONCLUSIONS: Initial PD appears to be a critical factor for achieving tight packing. PMID- 27001240 TI - The Importance of Exercise in the Well-Rounded Physician: Dialogue for the Inclusion of a Physical Fitness Program in Neurosurgery Resident Training. AB - Exercise, diet, and personal fitness programs are essentially lacking in modern graduate medical education. In the context of long hours and alternating shift and sleep cycles, the lack of exercise and poor dietary choices may have negative consequences on physician physical and mental health. This opinion piece aims to generate important dialogue regarding the scope of the problem, the literature supporting the health benefits of exercise, potential solutions to enhancing diet and exercise among resident trainees, and possible pitfalls to the adoption of exercise programs within graduate medical education. PMID- 27001242 TI - Electrocorticography Is Not Necessary During Awake Brain Surgery for Gliomas. PMID- 27001241 TI - Laparoscopic Treatment of Ventriculoperitoneal Shunt Complication Caused by Distal Catheter Isolation Inside the Falciform Ligament. AB - BACKGROUND: A ventriculoperitoneal shunt is a widely recognized treatment that we use to treat hydrocephalus. In one's lifetime, there is a high possibility of being diagnosed with shunt dysfunction. Occasionally, complications caused by the distal catheter located in the intra-abdominal cavity may occur. CASE DESCRIPTION: In this case, after undergoing shunt surgery, the patient's distal catheter had not moved and was fixed in 1 place. Therefore, we used abdominal computed tomography and discovered the presence of a pseudocyst where the distal catheter was located. Through laparoscopic-assisted surgery performed by the department of general surgery, we discovered that the distal catheter entered into the falciform ligament and caused it to expand, creating a cyst. The fascia of the falciform ligament was dissected using a harmonic scalpel. Cerebrospinal fluid and the distal catheter were noted. Afterwards, the distal catheter was placed into the peritoneal cavity. After surgery, the patient was discharged without any complications. CONCLUSIONS: Although this is an unusual circumstance, there have been reports of some cases in which the ventriculoperitoneal shunt distal catheter entered the falciform ligament. Therefore, one must pay close attention during the operation. In addition, when treatment is necessary, laparoscopic-assisted surgery might serve as an effective diagnostic and therapeutic modality. PMID- 27001243 TI - Efficacious and save use of biosimilar filgrastim for hematopoietic progenitor cell chemo-mobilization with vinorelbine in multiple myeloma patients. AB - Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio(r) combined with vinorelbine for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not been evaluated yet. We compared the efficacy of vinorelbine combined with this biosimilar filgrastim for HPC mobilization to vinorelbine plus original filgrastim (Neupogen(r)). Overall, 105 multiple myeloma patients received vinorelbine 35 mg/m2 intravenously on day 1 and either original filgrastim (n = 61;58%) or biosimilar filgrastim (n = 44;42%) at a dose of 5 ug per kg body weight (BW) twice daily subcutaneously starting day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and performed for a maximum of three consecutive days until at least 4 * 106 HPC/kg BW were collected. All patients proceeded to leukapheresis. In 102 (97%) patients the leukapheresis sessions were started as planned at day 8. The median number of collected HPC was 7.3 * 106 /kg BW (0.2-18.3) with original filgrastim compared to 9 * 106 /kg BW (4.2-23.8) with the biosimilar filgrastim (P = 0.16). HPC collection was successful in 57 (93%) of 61 patients of the original group and in all 44 (100%) patients of the biosimilar group (P = 0.14). No differences were observed regarding side effects. Duration of neutrophil engraftment after autologous HPC transplantation was similar between the two groups (P = 0.17). Biosimilar and original filgrastim achieve comparable results in combination with vinorelbine regarding HPC mobilization and transplantation outcome in multiple myeloma patients. J. Clin. Apheresis 32:21-26, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27001244 TI - Complexation thermodynamics of diglycolamide with f-elements: solvent extraction and density functional theory analysis. AB - Comparative extraction of trivalent lanthanide and actinide ions (La(3+), Eu(3+), Lu(3+), Am(3+) and Cm(3+)) with tetra-n-octyl diglycolamide (TODGA) was studied and showed the trend: Lu(3+) > Eu(3+) > Cm(3+) > Am(3+) > La(3+). The structure, bonding, energetic and thermodynamic parameters of the trivalent lanthanide and actinide ions (La(3+), Eu(3+), Lu(3+), Am(3+) and Cm(3+)) with a tridentate ligand, tetra-methyl diglycolamide (TMDGA), are reported in the gas and solvent phases in order to understand their complexation and extraction behaviour. The calculations were performed using the generalized gradient approximated BP86 density functional and the hybrid B3LYP functional using SVP and TZVPP basis sets. The calculated structure obtained at the BP86/SVP level of optimization was found to be in close agreement with the X-ray data and also with the structure obtained at the B3LYP/TZVP level of theory. The free energy of extraction was found to be exergonic for the explicit monomer water model. From the solvent extraction experiment the order of extraction was observed as Lu(3+) > Eu(3+) > Cm(3+) > Am(3+) > La(3+), which was in line with the trends predicted based on the free energy changes in the gas phase calculations (DeltaGgp). The Born-Haber thermodynamic cycle and the COSMO (conductor like screening model) solvation model were applied to calculate the free energy of extraction, DeltaGext, of lanthanide and actinide ions in the aqueous-dodecane biphasic system and DeltaGext, however, predicted different extraction trends. After dispersion correction (B3LYP-D3), the free energy of extraction for the metal ions was found to follow the order: Lu(3+) > Eu(3+) > La(3+), which was also observed in the solvent extraction experiments. Both COSMO and DCOSMO-RS models predict the same metal ion selectivity trend. Different bonding analyses indicate the electrostatic and less covalent nature of interactions between the ligands and the metal ions. PMID- 27001246 TI - A comparison of the Full Outline of UnResponsiveness (FOUR) score and Glasgow Coma Score (GCS) in predictive modelling in traumatic brain injury. AB - OBJECTIVES: To compare the performance of multivariate predictive models incorporating either the Full Outline of UnResponsiveness (FOUR) score or Glasgow Coma Score (GCS) in order to test whether substituting GCS with the FOUR score in predictive models for outcome in patients after TBI is beneficial. MATERIAL AND METHODS: A total of 162 TBI patients were prospectively enrolled in the study. Stepwise logistic regression analysis was conducted to compare the prediction of (1) in-ICU mortality and (2) unfavourable outcome at 3 months post-injury using as predictors either the FOUR score or GCS along with other factors that may affect patient outcome. The areas under the ROC curves (AUCs) were used to compare the discriminant ability and predictive power of the models. The internal validation was performed with bootstrap technique and expressed as accuracy rate (AcR). RESULTS: The FOUR score, age, the CT Rotterdam score, systolic ABP and being placed on ventilator within day one (model 1: AUC: 0.906 +/- 0.024; AcR: 80.3 +/- 4.8%) performed equally well in predicting in-ICU mortality as the combination of GCS with the same set of predictors plus pupil reactivity (model 2: AUC: 0.913 +/- 0.022; AcR: 81.1 +/- 4.8%). The CT Rotterdam score, age and either the FOUR score (model 3) or GCS (model 4) equally well predicted unfavourable outcome at 3 months post-injury (AUC: 0.852 +/- 0.037 vs. 0.866 +/- 0.034; AcR: 72.3 +/- 6.6% vs. 71.9%+/-6.6%, respectively). Adding the FOUR score or GCS at discharge from ICU to predictive models for unfavourable outcome increased significantly their performances (AUC: 0.895 +/- 0.029, p = 0.05; AcR: 76.1 +/- 6.5%; p < 0.004 when compared with model 3; and AUC: 0.918 +/- 0.025, p < 0.05; AcR: 79.6 +/- 7.2%, p < 0.009 when compared with model 4), but there was no benefit from substituting GCS with the FOUR score. CONCLUSION: Results showed that FOUR score and GCS perform equally well in multivariate predictive modelling in TBI. PMID- 27001245 TI - Mobile Phone Interventions for the Secondary Prevention of Cardiovascular Disease. AB - Mobile health in the form of text messaging and mobile applications provides an innovative and effective approach to promote prevention and management of cardiovascular disease (CVD); however, the magnitude of these effects is unclear. Through a comprehensive search of databases from 2002-2016, we conducted a quantitative systematic review. The selected studies were critically evaluated to extract and summarize pertinent characteristics and outcomes. A large majority of studies (22 of 28, 79%) demonstrated text messaging, mobile applications, and telemonitoring via mobile phones were effective in improving outcomes. Some key factors associated with successful interventions included personalized messages with tailored advice, greater engagement (2-way text messaging, higher frequency of messages), and use of multiple modalities. Overall, text messaging appears more effective than smartphone-based interventions. Incorporating principles of behavioral activation will help promote and sustain healthy lifestyle behaviors in patients with CVD that result in improved clinical outcomes. PMID- 27001247 TI - THE GHOST IN THE MACHINE? THE VALUE OF EXPERT ADVICE IN THE PRODUCTION OF EVIDENCE-BASED GUIDANCE: A MIXED METHODS STUDY OF THE NICE INTERVENTIONAL PROCEDURES PROGRAMME. AB - OBJECTIVES: The aim of this study was to determine the aspects of expert advice that decision makers find most useful in the development of evidence-based guidance and to identify the characteristics of experts providing the most useful advice. METHODS: First, semi-structured interviews were conducted with seventeen members of the Interventional Procedures Advisory Committee of the UK's National Institute of Health and Care Excellence. Interviews examined the usefulness of expert advice during guidance development. Transcripts were analyzed inductively to identify themes. Second, data were extracted from 211 experts' questionnaires for forty-one consecutive procedures. Usefulness of advice was scored using an index developed through the qualitative work. Associations between usefulness score and characteristics of the expert advisor were investigated using univariate and multivariate analyses. RESULTS: Expert opinion was seen as a valued complement to empirical evidence, providing context and tacit knowledge unavailable in published literature, but helpful for interpreting it. Interviewees also valued advice on the training and experience required to perform a procedure, on patient selection criteria and the place of a procedure within a clinical management pathway. Limitations of bias in expert opinion were widely acknowledged and skepticism expressed regarding the anecdotal nature of advice on safety or efficacy outcomes. Quantitative analysis demonstrated that the most useful advice was given by clinical experts with direct personal experience of the procedure, particularly research experience. CONCLUSIONS: Evidence-based guidance production is often characterized as a rational, pipeline process. This ignores the valuable role that expert opinion plays in guidance development, complementing and supporting the interpretation of empirical data. PMID- 27001248 TI - Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study. AB - Protein-bound uraemic toxins (PBUTs) cause various deleterious effects in end stage kidney disease patients, because their removal by conventional haemodialysis (HD) is severely limited by their low free fraction in plasma. Here we provide an experimental validation of the concept that the HD dialytic removal of PBUTs can be significantly increased by extracorporeal infusion of PBUT binding competitors. The binding properties of indoxyl sulfate (IS), indole-3 acetic acid (IAA) and hippuric acid (HIPA) and their binding competitors, ibuprofen (IBU), furosemide (FUR) and tryptophan (TRP) were studied in uraemic plasma. The effect of binding competitor infusion on fractional removal of PBUT was then quantified in an ex vivo single-pass HD model using uraemic human whole blood. The infusion of a combination of IBU and FUR increased the fractional removal of IS from 6.4 +/- 0.1 to 18.3 +/- 0.4%. IAA removal rose from 16.8 +/- 0.3 to 34.5 +/- 0.7%. TRP infusion increased the removal of IS and IAA to 10.5 +/ 0.1% and 27.1 +/- 0.3%, respectively. Moderate effects were observed on HIPA removal. Pre-dialyzer infusion of PBUT binding competitors into the blood stream can increase the HD removal of PBUTs. This approach can potentially be applied in current HD settings. PMID- 27001249 TI - New cytotoxic compounds of endophytic fungus Alternaria sp. isolated from Broussonetia papyrifera (L.) Vent. AB - From the ethyl acetate extract of a culture of the endophytic fungus Alternaria species G7 in Broussonetia papyrifera, a new compound altertoxin IV (1) together with nine known compounds were isolated and identified by means of bioassay guided fractionation. The structures of these compounds were established on the basis of spectroscopic methods, among which the absolute configuration of compound 1, a new tetrahydroperylenone derivative, was determined by means of X Ray Crystallographic analysis. The isolated compounds were subjected to cytotoxic activity against three human cancer cell lines (A549, MG-63, and SMMC-7721). Compound 2 showed significant cytotoxic activities against tested cell lines, with IC50 values of 1.47, 2.11 and 7.34 MUg/mL, respectively. Additionally, compound 4 also exhibited significant cytotoxic activities against cell lines MG 63 and SMMC-7721, with IC50 values of 0.53 and 2.92 MUg/mL. Endophytic fungi Alternaria from B. papyrifera might be promising sources of natural bioactive and novel metabolites. PMID- 27001250 TI - Assessment of the incidence of squamous cell papilloma of the esophagus and the presence of high-risk human papilloma virus. AB - BACKGROUND AND AIMS: There has been a recent increase in the incidence of oropharyngeal cancer (OPC) associated with high-risk human papilloma virus (HPV) infection. We investigated the incidence of esophageal papilloma and the presence of high-risk HPV infection. METHODS: This is a cross-sectional study conducted at a County teaching hospital. Patients with esophageal papilloma between January 2000 and December 2013 were identified. Patients with sufficient specimens were tested for the HPV virus. RESULTS: Sixty patients with esophageal papilloma lesions were identified from 2000 to 2013. (31 males, age 51 +/- 13 years). The incidence was 0.13% in 2000 and increased to 0.57% in 2013 (P < 0.0001). Twenty nine patients (48.3%) had a papilloma that was more than 5 mm in size, and 20% had multiple lesions. The papilloma was located in the distal esophagus in 35 (58.3%) patients, mid esophagus in 17 (28.3%) patients, and proximal in 8 (13.3%) patients. Three (5%) patients had associated OPC, and 9 (47.4%) of the 19 patients tested were positive for high-risk HPV serotype 16. CONCLUSIONS: The incidence of esophageal papilloma has increased by fourfolds over the past 14 years. About half of the tested patients demonstrated high risk HPV. This may suggest a potential growing risk for esophageal squamous cell cancer in the future. PMID- 27001251 TI - Holistic processing for bodies and body parts: New evidence from stereoscopic depth manipulations. AB - Although holistic processing has been documented extensively for upright faces, it is unclear whether it occurs for other visual categories with more extensive substructure, such as body postures. Like faces, body postures have high social relevance, but they differ in having fine-grain organization not only of basic parts (e.g., arm) but also subparts (e.g., elbow, wrist, hand). To compare holistic processing for whole bodies and body parts, we employed a novel stereoscopic depth manipulation that creates either the percept of a whole body occluded by a set of bars, or of segments of a body floating in front of a background. Despite sharing low-level visual properties, only the stimulus perceived as being behind bars should be holistically "filled in" via amodal completion. In two experiments, we tested for better identification of individual body parts within the context of a body versus in isolation. Consistent with previous findings, recognition of body parts was better in the context of a whole body when the body was amodally completed behind occluders. However, when the same bodies were perceived as floating in strips, performance was significantly worse, and not significantly different, from that for amodally completed parts, supporting holistic processing of body postures. Intriguingly, performance was worst for parts in the frontal depth condition, suggesting that these effects may extend from gross body organization to a more local level. These results provide suggestive evidence that holistic representations may not be "all-or-none," but rather also operate on body regions of more limited spatial extent. PMID- 27001252 TI - High apolipoprotein M serum levels correlate with chronic obstructive pulmonary disease. AB - BACKGROUND: Recently, variations in a component of high-density lipoprotein (HDL), namely apolipoprotein M (apoM), were found to be associated with chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the association between apoM and COPD severity. Factors associated with apoM, COPD, or coronary artery disease (CAD) were also assessed. METHODS: A total of 110 COPD patients and 110 age- and sex-matched non-COPD controls were included. Among them, thirty COPD patients and seven non-COPD controls had CAD. ApoM and pentraxin-3 levels were measured by ELISA. Additionally, the levels of high sensitivity C-reactive protein (hs-CRP), cholesterol, and triglyceride were assessed using an automatic biochemical analyzer. RESULTS: Serum apoM levels increased gradually with COPD severity, with the most prominent apoM elevation observed in very severe COPD cases. In addition, ApoM was correlated with percent predicted forced expiratory volume in one second (% predicted FEV1) (r = -0.38, P < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = 0.23, P < 0.017), and hs-CRP (r = 0.24, P = 0.01) in COPD patients. Furthermore, apoM was shown to be a risk factor for COPD onset (OR = 1.095, 95% CI = 1.034-1.160, P = 0.002), but not associated with CAD in COPD patients. CONCLUSIONS: Serum apoM was elevated in COPD patients and increased gradually with COPD severity. However, there was no association between apoM and CAD development in COPD patients. PMID- 27001253 TI - Cleansing effect of acidic L-arginine on human oral biofilm. AB - BACKGROUND: Dental plaque formed on tooth surfaces is a complex ecosystem composed of diverse oral bacteria and salivary components. Accumulation of dental plaque is a risk factor for dental caries and periodontal diseases. L-arginine has been reported to decrease the risk for dental caries by elevating plaque pH through the activity of arginine deiminase in oral bacteria. Here we evaluated the potential of L-arginine to remove established oral biofilms. METHODS: Biofilms were formed using human saliva mixed with Brain Heart Infusion broth supplemented with 1 % sucrose in multi-well plates or on plastic discs. After washing the biofilms with saline, citrate (10 mM, pH3.5), or L-arginine (0.5 M, pH3.5), the retained biofilms were analyzed by crystal violet staining, scanning electron microscopy, and Illumina-based 16S rDNA sequencing. RESULTS: Washing with acidic L-arginine detached oral biofilms more efficiently than saline and significantly reduced biofilm mass retained in multi-well plates or on plastic discs. Illumina-based microbiota analysis showed that citrate (pH3.5) preferentially washed out Streptococcus from mature oral biofilm, whereas acidic L-arginine prepared with 10 mM citrate buffer (pH3.5) non-specifically removed microbial components of the oral biofilm. CONCLUSIONS: Acidic L-arginine prepared with citrate buffer (pH3.5) effectively destabilized and removed mature oral biofilms. The acidic L-arginine solution described here could be used as an additive that enhances the efficacy of mouth rinses used in oral hygiene. PMID- 27001254 TI - Rates and consequences of posttraumatic distress among American Indian adults with type 2 diabetes. AB - This study examined the prevalence of screened posttraumatic stress disorder (PTSD) and associated diabetes-related outcomes. A sample of American Indian adults with type 2 diabetes (n = 218) participated in interviewer-administered surveys. Using a cutoff of 3 on the Primary Care PTSD screener, 21.8 % of participants screened positive for PTSD. PTSD symptoms were negatively associated with self-rated health status and positively associated with past year hospitalization after controlling for several demographic factors, but not after controlling for depressive symptoms. Past month frequency of hyperglycemia symptoms was not related to PTSD symptoms. When grouped by mental health conditions (neither screened PTSD nor depressive symptoms, screened PTSD only, depressive symptoms only, and both), those with both screened PTSD and depressive symptoms reported the highest proportion of any past month hyperglycemia, past year hospitalization, and low self-rated health status. Screened PTSD, especially in those with comorbid depressive symptoms, is an important consideration in diabetes care. PMID- 27001255 TI - An evaluation of factors associated with sexual risk taking among Black men who have sex with men: a comparison of younger and older populations. AB - In the United States, rates of human immunodeficiency virus (HIV) infection are highest among Black men who have sex with men (BMSM). Prior research indicates that younger BMSM in particular (i.e., BMSM 29 years of age and younger) are most at risk for HIV infection, and that HIV incidence in this subpopulation has risen in recent years. It remains unclear, however, why younger BMSM, relative to BMSM 30 years of age and older, are at increased risk for HIV infection. For the current study, we surveyed 450 BMSM located in the Atlanta, GA metropolitan and surrounding areas. We assessed BMSM's depressive symptoms, substance use during sex, psycho-social risk factors (i.e., HIV risk perceptions, condom use self efficacy, internalized homophobia, and perceived HIV stigmatization), and sexual risk taking (i.e., condomless anal intercourse [CAI]). We found that younger BMSM (YBMSM) and older BMSM (OBMSM) differed with respect to factors associated with CAI. In multivariable models, alcohol use before or during sex, lower educational attainment, and sexual orientation (i.e., bisexual sexual orientation) were significantly associated with increased CAI for YBMSM, while HIV risk perceptions and internalized homophobia were significantly, negatively associated with CAI among OBMSM. Rates of engaging in CAI were similar across the two age cohorts; however, factors related to CAI varied by these two groups. Findings emphasize the need to consider targeted interventions for different generational cohorts of BMSM. PMID- 27001256 TI - Dizziness and vestibular function before and after cochlear implantation. AB - Vestibular problems after cochlear implantation (CI) were explored by categorizing them according to clinical course and changes in objective vestibular function. The changes in vestibular function of 62 patients (66 ears) were analyzed and vestibular symptoms were divided into three categories by their time course and nature. Etiologies were determined by analyzing the symptoms in combination with changes in objective vestibular function, measured using the caloric and/or video head impulse test. Before surgery, vestibular function was normal in 31 cases (47.0 %), unilaterally hypofunctional in 14 (21.2 %), and bilaterally hypofunctional in 21 (31.8 %). Eight cases (12.1 %) reported dizziness before surgery. A total of 18 cases (27.3 %) experienced postoperative dizziness. Ten patients experienced immediate transient dizziness (including 2 cases of benign positional paroxysmal vertigo); four experienced immediate prolonged dizziness (including 3 cases of bilateral vestibular hypofunction); and four experienced recurrent episodic dizziness (including 3 cases of suspicious endolymphatic hydrops). The sums of the maximal slow-phase velocities (SPVs) of the implanted ears were changed from 22.70 +/- 17.31 to 12.55 +/- 12.02 degrees /s after implantation (p = 0.004) with very little changes in the other side (32.65 +/- 24.85-31.40 +/- 29.10 degrees /s). Careful review of vestibular status is an important step, especially when deciding implantation in the only vestibular functioning ear or bilateral implantation. PMID- 27001258 TI - Conditions for making trial data available to other investigators. PMID- 27001257 TI - Woodworkers and the inflammatory effects of softwood/hardwood dust: evidence from nasal cytology. AB - Our primary aim was to use nasal cytology to compare a group of woodworkers with a group of unexposed subjects to see whether wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary aim was to seek any differences in nasal symptoms or nasal cytology between workers exposed to softwood vs hardwood dust, thereby comparing the inflammatory harmful potential of the two woods. Among 117 woodworkers at factories in the Veneto region (Italy), 40 exposed to either softwood or hardwood dust were assessed by means of a questionnaire, nasal cytology, and personal wood dust sampling, and compared with 40 unexposed controls. Woodworkers reported significantly more nasal symptoms than controls (p = 0.0007). The woodworker group's nasal smears contained significantly more neutrophils (p < 0.00001) and lymphocytes (p = 0.02) than the control group's. The softwood workers had significantly lower levels of personal exposure to wood dust than the hardwood workers (p = 0.04); there were no significant differences in age, history of cigarette smoking, or period of exposure between these two sub-cohorts of woodworkers. A statistical trend indicated that softwood workers had more eosinophils (p = 0.05) and lymphocytes (p = 0.05) in their rhinocytograms. Nasal cytology revealed chronic inflammatory rhinitis in a significant proportion of woodworkers' enroled in this study. It also suggested a different harmful potential for softwood and hardwood dust. Nasal cytology could prove useful in screening woodworkers for chronic inflammatory rhinitis. Further investigations are needed to examine the role of different types of wood dust in nasal inflammation. PMID- 27001259 TI - N-Methylated alpha-Amino Acids And Peptides: Synthesis And Biological Activity. AB - The simplest and minimal modification of a single amino acid or peptide bonds is represented by N-methylation. This can improve the pharmacokinetic properties of biologically active peptides as well as resulting in analogues that show specific biological activity such as enzyme inhibitors, receptor antagonists and agonists, building blocks in combinatorial chemistry for the screening of new potential drugs. Further, structural and conformational studies performed with N-methylated analogues of natural amino acids and peptides enabled to (i) produce stable foldamers with different topology with respect to the helix of natural and endogenous peptides, (ii) confer to modified peptides high stability against proteases and (iii) enhance lipophilicity and bioavailability for pharmacological purposes. Consequentially, it is crucial to provide optically pure N-methyl-amino acids and N-methylated peptides with a large supply. The present report will focus on the results obtained in the last decade in the field of chemical synthetic methodologies for the N-methylation of amino acids. PMID- 27001260 TI - Differing effects of high-fat or high-carbohydrate meals on food hedonics in overweight and obese individuals. AB - Although the effects of dietary fat and carbohydrate on satiety are well documented, little is known about the impact of these macronutrients on food hedonics. We examined the effects of ad libitum and isoenergetic meals varying in fat and carbohydrate on satiety, energy intake and food hedonics. In all, sixty five overweight and obese individuals (BMI=30.9 (sd 3.8) kg/m2) completed two separate test meal days in a randomised order in which they consumed high-fat/low carbohydrate (HFLC) or low-fat/high-carbohydrate (LFHC) foods. Satiety was measured using subjective appetite ratings to calculate the satiety quotient. Satiation was assessed by intake at ad libitum meals. Hedonic measures of explicit liking (subjective ratings) and implicit wanting (speed of forced choice) for an array of HFLC and LFHC foods were also tested before and after isoenergetic HFLC and LFHC meals. The satiety quotient was greater after ad libitum and isoenergetic meals during the LFHC condition compared with the HFLC condition (P=0.006 and P=0.001, respectively), whereas ad libitum energy intake was lower in the LFHC condition (P<0.001). Importantly, the LFHC meal also reduced explicit liking (P<0.001) and implicit wanting (P=0.011) for HFLC foods compared with the isoenergetic HFLC meal, which failed to suppress the hedonic appeal of subsequent HFLC foods. Therefore, when coupled with increased satiety and lower energy intake, the greater suppression of hedonic appeal for high-fat food seen with LFHC foods provides a further mechanism for why these foods promote better short-term appetite control than HFLC foods. PMID- 27001261 TI - A high-throughput screening strategy for accurate quantification of menaquinone based on fluorescence-activated cell sorting. AB - To enhance the screening efficiency and accuracy of a high-yield menaquinone (vitamin K2, MK) bacterial strain, a novel, quantitative method by fluorescence activated cell sorting (FACS) was developed. The staining technique was optimized to maximize the differences in fluorescence signals between spontaneous and MK accumulating cells. The fluorescence carrier rhodamine 123 (Rh123), with its ability to reflect membrane potential, proved to be an appropriate fluorescent dye to connect the MK content with fluorescence signal quantitatively. To promote adequate access of the fluorescent molecule to the target and maintain higher cell survival rates, staining and incubation conditions were optimized. The results showed that 10 % sucrose facilitated uptake of Rh123, while maintaining a certain level of cell viability. The pre-treatment of cells with MgCl2 before staining with Rh123 also improved cell viability. Using FACS, 50 thousands cells can easily be assayed in less than 1 h. The optimized staining protocol yielded a linear response for the mean fluorescence against high performance liquid chromatography-measured MK content. We have developed a novel and useful staining protocol in the high-throughput evaluation of Flavobacterium sp. mutant libraries, using FACS to identify mutants with increased MK-accumulating properties. This study also provides reference for the screening of other industrial microbial strains. PMID- 27001262 TI - Characterization of a salt-activated protease with temperature-dependent secretion in Stenotrophomonas maltophilia FF11 isolated from frozen Antarctic krill. AB - Seafood is sometimes wasted due to the growth of psychrotolerant microbes which secrete proteases and break down proteins. Stenotrophomonas maltophilia FF11, isolated from frozen Antarctic krill, grows at a wide range of temperatures and secretes more proteases at low temperatures. According to zymogram analysis, two kinds of proteases were produced from this strain. A major protease was produced largely at 15 degrees C, but not at 37 degrees C. The temperature-dependent secreted protease was purified to homogeneity. Its molecular mass was determined at 37.4 kDa and its amino acid sequence was also obtained. This protease is a member of the subtilase group according to the NCBI blast analysis. The enzyme was highly stable at high salt concentration (4 M). Interestingly, its activity increased about 1.6-fold under high salt condition. The enzyme remains active and stable in different organic solvents (50 %, v/v) such as dimethylsulfoxide, dimethyl formamide, dioxane and acetone. These properties may provide potential applications in quality control for sea foods, in protein degradation at high salt concentration, in biocatalysis and biotransformation within non-aqueous media, such as detergent and transesterification. PMID- 27001263 TI - Indoxyl sulfate promotes vascular smooth muscle cell calcification via the JNK/Pit-1 pathway. AB - We determined the effect of indoxyl sulfate (IS) on Pit-1 expression and the role of Pit-1 in IS-induced osteoblastic differentiation and calcification of vascular smooth muscle cells (VSMCs). To assess osteoblastic differentiation and Pit-1 expression, VSMCs were incubated with various concentrations of IS for different durations. Phosphonoformic acid (PFA), a competitive inhibitor of Pit-1, was used to verify the role of Pit-1. Western blot analysis and quantitative real-time polymerase chain reaction (PCR) were performed to assess Pit-1 protein and mRNA levels, respectively. To evaluate calcification, calcium content was measured. After IS treatment, we observed osteoblastic differentiation and calcification of VSMCs and up-regulation of Pit-1 expression. Moreover, the effect of IS on osteoblastic differentiation and Pit-1 expression was partly dose- and time dependent. PFA abrogated the IS-induced osteoblastic differentiation and calcification of VSMCs to a certain extent. The c-Jun N-terminal kinase (JNK) pathway was activated after treatment with IS, whereas inhibition of the JNK pathway partially attenuated the effect of IS on both the stimulation of Pit-1 expression and calcium deposition. Our study is the first to demonstrate that IS promotes Pit-1 expression in part by activation of the JNK pathway that is involved in the mechanism of IS-induced osteoblastic differentiation and matrix mineralization. PMID- 27001264 TI - Hypertension Is Associated With Undiagnosed OSA During Rapid Eye Movement Sleep. AB - BACKGROUND: Evidence linking OSA with hypertension in population studies is conflicting. We examined longitudinal and cross-sectional associations of previously unrecognized OSA, including OSA occurring in rapid eye movement (REM) sleep, with hypertension. METHODS: The Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study is a longitudinal study of community dwelling men in Adelaide, South Australia. Biomedical assessments at baseline (2002-2006) and follow-up (2007-2010) identified hypertension (systolic >= 140 mm Hg and/or diastolic >= 90 mm Hg, or medication) and risk factors. In 2010 to 2011, 837 men without a prior diagnosis of OSA underwent full in-home unattended polysomnography of whom 739 recorded >= 30 min of REM sleep. Hypertension at follow-up (concomitant with OSA status) was defined as prevalent hypertension. Recent-onset hypertension was defined as hypertension at biomedical follow-up (56 months mean follow-up [range, 48-74]) in men free of hypertension at baseline. RESULTS: Severe REM OSA (apnea hypopnea index >=30/h) showed independent adjusted associations with prevalent (OR, 2.40, 95% CI, 1.42-4.06), and recent-onset hypertension (2.24 [1.04-4.81]). Significant associations with non-REM AHI were not seen. In men with AHI < 10, REM OSA (apnea hypopnea index) >= 20/h was significantly associated with prevalent hypertension (2.67 [1.33-5.38]) and the relationship with recent-onset hypertension was positive but not statistically significant (2.32 [0.79-6.84]). Similar results were seen when analyses were confined to men with non-REM AHI < 10. CONCLUSIONS: In men not considered to have OSA (AHI < 10), hypertension was associated with OSA during REM sleep. REM OSA may need consideration as an important clinical entity requiring treatment but further systematic assessment and evidence is needed. PMID- 27001266 TI - Severely Calcified and Dilated Meandering Mesenteric Artery Complicating Abdominal Aorta Stenosis. PMID- 27001265 TI - Elevated Levels of Circulating Bone Morphogenetic Protein 7 Predict Mortality in Pulmonary Arterial Hypertension. AB - BACKGROUND: This study aimed to show whether circulating bone morphogenetic proteins (BMPs) levels are associated with increased risk of mortality in patients with pulmonary arterial hypertension (PAH). METHODS: A total of 156 patients with PAH including 43 with heritable PAH (HPAH) and 113 with idiopathic PAH (IPAH) diagnosed by gene screening were enrolled in the study. Circulating BMPs were measured by ELISA in plasma samples from patients with HPAH (n = 43) and IPAH (n = 113) and from control subjects (n = 51). Clinical characteristics at baseline and long-term survival were compared according to the different BMP levels. RESULTS: Patients with HPAH had significantly higher BMP7 concentrations than patients with IPAH and control subjects (20.1 [interquartile range (IQR), 9.4, 55.2] vs 6.5 [IQR, 3.5, 11.7] and 2.5 [IQR, 0.9, 6.6] pg/mL, respectively; P < .001). Elevated plasma BMP7 were associated with a higher risk of mortality after adjustment for sex, 6-minute walk distance, mean right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (HR, 1.904; 95% CI, 1.021-3.551; P = .043). Patients with IPAH with a BMP7 level > 7.85 pg/mL had a higher risk of mortality than those with a low BMP7 concentration (P = .042, log-rank test). CONCLUSIONS: Levels of circulating BMP7 correlate with mortality in PAH, and may be a predictor of disease in patients with HPAH and IPAH. PMID- 27001267 TI - Stratifying Risk in Barrett's Esophagus With Low-grade Dysplasia: Making the Best of a (Not So) Bad Situation. PMID- 27001268 TI - Letter to "Statin Use Is Associated With Reduced Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases". PMID- 27001269 TI - Preconception Care Reduces Relapse of Inflammatory Bowel Disease During Pregnancy. AB - BACKGROUND & AIMS: Women with inflammatory bowel disease (IBD) may have incorrect beliefs about their disease and its medication in relation to pregnancy. We studied the effects of preconception care (PCC) on patients' behavior during pregnancy, disease relapse during pregnancy, and birth outcomes. METHODS: In a prospective study, we followed up all women with IBD seen at the preconception outpatient clinic at Erasmus MC-University Medical Center in Rotterdam, The Netherlands (from 2008 through 2014). We compared patients who received PCC before they became pregnant (PCC group; n = 155) with patients who visited the clinic after they already were pregnant (no-PCC group; n = 162). We collected data on lifestyle, medication adherence, planning of conception, disease activity, and birth outcomes. We compared adherence to medical advice, rates of disease relapse during pregnancy, and birth outcomes. RESULTS: The PCC group was on average younger than the no-PCC group (29.7 vs 31.4 y; P = .001), and a greater proportion were nulliparous (76.1% vs 51.2%; P = .0001). PCC was associated with adherence to IBD medication during pregnancy (adjusted odds ratio [aOR],5.69; 95% confidence interval [CI], 1.88-17.27), adequate folic acid intake (aOR, 5.26; 95% CI, 2.70-10.26), and smoking cessation (aOR, 4.63; 95% CI, 1.22 17.55). PCC reduced disease relapse during pregnancy independent of parity, disease duration, or disease activity before conception (aOR, 0.51; 95% CI, 0.28 0.95). The PCC group was less likely to deliver babies of low birth weight (aOR, 0.08; 95% CI, 0.01-0.48). CONCLUSIONS: In a prospective study, we found that preconception care reduces IBD relapse during pregnancy by promoting adherence to medication and smoking cessation. Preconception also reduces risk for babies of low birth weight. PMID- 27001270 TI - Genetic association and stress mediated down-regulation in trabecular meshwork implicates MPP7 as a novel candidate gene in primary open angle glaucoma. AB - BACKGROUND: Glaucoma is the largest cause of irreversible blindness affecting more than 60 million people globally. The disease is defined as a gradual loss of peripheral vision due to death of Retinal Ganglion Cells (RGC). The RGC death is largely influenced by the rate of aqueous humor production by ciliary processes and its passage through the trabecular meshwork (TM) in the anterior part of the eye. Primary open angle glaucoma (POAG), the most common subtype, is a genetically complex disease. Multiple genes and many loci have been reported to be involved in POAG but taken together they explain less than 10 % of the patients from a genetic perspective warranting more studies in different world populations. The purpose of this study was to perform genome-wide search for common variants associated with POAG in an east-Indian population. METHODS: The study recruited 746 POAG cases and 697 controls distributed into discovery and validation cohorts. In the discovery phase, genome-wide genotype data was generated on Illumina Infinium 660 W-Quad platform and the significant SNPs were genotyped using Illumina GGGT assay in the second phase. Logistic regression was used to test association in the discovery phase to adjust for population sub structure and chi-square test was used for association analysis in validation phase. Publicly available expression dataset for trabecular meshwork was used to check for expression of the candidate gene under cyclic mechanical stress. Western blot and immunofluorescence experiments were performed in human TM cells and murine eye, respectively to check for expression of the candidate gene. RESULTS: Meta-analysis of discovery and validation phase data revealed the association of rs7916852 in MPP7 gene (p = 5.7x10(-7)) with POAG. We have shown abundant expression of MPP7 in the HTM cells. Expression analysis shows that upon cyclic mechanical stress MPP7 was significantly down-regulated in HTM (Fold change: 2.6; p = 0.018). MPP7 protein expression was also found to be enriched in the ciliary processes of the murine eye. CONCLUSION: Using a genome-wide approach we have identified MPP7 as a novel candidate gene for POAG with evidence of its expression in relevant ocular tissues and dysregulation under mechanical stress possibly mimicking the disease scenario. PMID- 27001272 TI - Skin Absorption of Anions: Part Two. Skin Absorption of Halide Ions. AB - PURPOSE: The purpose of the study was to sort skin penetration of anions with respect to their properties and to assess their mechanisms of penetration. METHODS: Aqueous solutions of halides at two concentrations were prepared and quantitative penetration studies were carried out for 24 h using Franz diffusion cells. The iodide permeation was also measured after blocking of anion channels and transporters to investigate the role of this specific transport. RESULTS: Absorption of halide ions into skin revealed large differences of transport between these anions according to the Hofmeister series. Increasing steady-state fluxes and lag times in the order F(-) < Cl(-) < Br(-) < I(-) were observed in permeation experiments. The steady-state fluxes were proportional to the concentration for each halide ion. Longer lag times for iodide or bromide ions were explained by the ability of such sticky chaotropic anions to interact with apolar lipids especially in the stratum corneum. Inhibiting ion exchangers and channels decreased the flux of iodide ions by 75%, showing the high contribution of the facilitated transport over the passive pathway. CONCLUSION: Ions transport had contributions coming from passive diffusion through the skin layers and transport mediated by ion channels and binding to ion transporters. PMID- 27001274 TI - Twin metabolomics: the key to unlocking complex phenotypes in nutrition research. AB - Twin studies are a valuable resource for studying phenotypes and their underlying biology. Heritability estimates based on the classic twin model show that genes influence human traits including health, diet, and food choice. Metabolomics is a promising tool in nutrition and health research where complex metabolite profiles reflect the metabolic effects of foods and diets as well as the biological pathways associated with diet-related diseases. In recent years, publications arising from twin research have incorporated metabolomic analysis, providing insights into genetic and environmental influences on metabolomic profiles. This article reviews the application of metabolomics in twin research with a particular focus on nutrition and diet-related diseases. The review begins by describing the classic twin study design, followed by a look at its application in nutrition research. Indeed, there is clear evidence for a genetic influence on dietary intake, regardless of the outcome measure: energy, macronutrients, dietary patterns, or food choice. The latter part of the review introduces metabolomic research showing how twin studies can separate aspects of the metabolome that are strongly influenced by genetics vs those that are more influenced by environment. The combination of metabolomics and twin research brings the promise of untangling gene-environment effects on complex phenotypes such as the metabolome, obesity, and diet-related diseases. For example, metabolomics is used in nutrition research to identify metabolites associated with particular dietary patterns. When combined within a twin study design, heritability of metabolite-dietary pattern associations can be established allowing further insight into complex gene-environment interactions that shape individual metabolomes. PMID- 27001273 TI - Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence. AB - Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals. PMID- 27001275 TI - Cinnamon users with prediabetes have a better fasting working memory: a cross sectional function study. AB - Working memory (WM) is impaired in prediabetes. We hypothesized that culinary herbs and spices may decrease insulin resistance (IR) and improve WM in prediabetes. Healthy people aged >=60 years with prediabetes (fasting blood glucose 100-125 mg/dL) (47 men and 46 women) whose food and culinary herb intakes were established with a food frequency questionnaire had body composition assessed and fasting glucose and insulin measured. Working memory and Mini-Mental State Examination (MMSE) were assessed on the same occasion. The contributions to associations between WM and diet, body fat, and IR were estimated by linear regression. Compared with nonusers, cinnamon users had significantly less frequent physical activity (2.9 vs. 4.4 times per week) and more often used fresh ginger (93.3% vs. 64.1%) and ginger in cooking (60.0% vs. 32.1%). Cinnamon users also had a better WM (2.9 vs. 2.5, P < .001). Cinnamon had a significant effect (users were 0.446 higher), but not ginger or curry usage, in predicting WM. For sociodemographic variables, only education (years) was significant in predicting WM (beta = 0.065). Other significant determinants of WM were total fat mass (kilograms) (beta = -0.024) and MMSE (beta = 0.075). After adjustment for age and sex, cinnamon use, education, and MMSE remained significant individual predictors. In the final model, in which all variables listed were adjusted simultaneously, cinnamon users still had a significantly higher WM than nonusers. Cinnamon usage is associated with a better WM, not accounted for by dietary quality or IR, in untreated prediabetes. PMID- 27001276 TI - Circulating adiponectin concentrations are increased by dietary resistant starch and correlate with serum 25-hydroxycholecalciferol concentrations and kidney function in Zucker diabetic fatty rats. AB - We previously reported that dietary resistant starch (RS) type 2 prevented proteinuria and promoted vitamin D balance in type 2 diabetic (T2D) rats. Here, our primary objective was to identify potential mechanisms that could explain our earlier observations. We hypothesized that RS could promote adiponectin secretion and regulate the renin-angiotensin system activity in the kidney. Lean Zucker rats (n = 5) were fed control diet; Zucker diabetic fatty rats (n = 5/group) were fed either an AIN-93G control diet (DC) or AIN-93G diet containing either 10% RS or 20% RS (HRS) for 6 weeks. Resistant starch had no impact on blood glucose concentrations and hemoglobin A1c percentage, yet circulating adiponectin was 77% higher in HRS-fed rats, compared to DC rats. Adiponectin concentrations strongly correlated with serum 25-hydroxycholecalciferol (r = 0.815; P < .001) and urinary creatinine concentrations (r = 0.818; P < .001) and inversely correlated with proteinuria (r = -0.583; P = .02). Serum angiotensin II concentrations were 44% lower, and expression of the angiotensin II receptor, type 1, was attenuated in RS-fed rats. Moreover, we observed a 14-fold increase in messenger RNA expression of nephrin, which is required for functioning of the renal filtration barrier, in HRS rats. The HRS, but not 10% RS diet, increased circulating 25 hydroxycholecalciferol concentrations and attenuated urinary loss of vitamin D metabolites in Zucker diabetic fatty rats. Taken together, we provide evidence that vitamin D balance in the presence of hyperglycemia is strongly associated with serum adiponectin levels and reduced renal renin-angiotensin system signaling. PMID- 27001277 TI - A high-fat diet increases body weight and circulating estradiol concentrations but does not improve bone structural properties in ovariectomized mice. AB - Bone health is influenced by body mass and estrogen. The objective of the study was to determine whether high-fat diet-induced obesity affects bone structure and alters markers of bone turnover in ovariectomized (OVX) mice. We hypothesized that a high-fat diet would increase body weight gain and serum estradiol levels in OVX mice but would not improve bone structural parameter in OVX mice. Thirty five C57BL/6 mice were either sham operated or OVX at the age of 4 months and then fed either a normal-fat diet (10% energy as fat) or a high-fat diet (45% energy as fat with extra fat from lard) ad libitum for 11 weeks. Ovariectomy increased body weight, serum tartrate-resistant acid phosphatase concentration, and expression of cathepsin K in bone; decreased serum estradiol concentration; and induced significant bone loss manifested by decreased bone volume/total volume (BV/TV), connectivity density (Conn.D), trabecular number, and trabecular thickness with increased trabecular separation and structural model index (P < .01). The high-fat diet increased body weight (P < .01) in OVX mice and nonsignificantly decreased BV/TV (P = .08) and Conn.D (P = .10). Despite having similar serum estradiol concentrations and higher body weight, OVX mice consuming the high-fat diet had lower BV/TV, Conn.D, trabecular number, trabecular thickness, and higher structural model index and trabecular separation than did sham mice fed the normal-fat diet. These findings indicate that increased body weight and elevated serum estradiol concentration induced by a high-fat diet do not mitigate ovariectomy-induced bone loss in mice. PMID- 27001278 TI - Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism. AB - We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. PMID- 27001279 TI - Lactobacillus sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression. AB - A high-fat diet (HFD) induces obesity and the associated increases in blood glucose and inflammation through changes in gut microbiota, endotoxemia, and increased gut permeability. To counteract this, researchers have suggested that the use of probiotics that suppress production of proinflammatory lipopolysaccharide (LPS). Here, we tested whether Lactobacillus sakei OK67, which inhibits gut microbiota LPS production selected from among the lactic acid bacteria isolated from kimchi, exerted antihypoglycemic or anti-inflammatory effects in HFD-fed mice. Mice were randomly divided into 2 groups and fed an HFD or a low-fat diet for 4 weeks. These groups were further subdivided; 1 subgroup was treated with L sakei OK67 and fed the experimental diet for 4.5 weeks, whereas the other subgroup was fed the experimental diet alone. L sakei OK67 treatment lowered HFD-elevated LPS levels in blood and colonic fluid and significantly decreased HFD-elevated fasting blood glucose levels and the area under the curve in an oral glucose tolerance test. L sakei OK67 treatment inhibited HFD-induced body and epididymal fat weight gains, suppressed HFD induced tumor necrosis factor-alpha and interleukin-1beta expression and nuclear factor-kappaB activation in the colon, and significantly increased HFD-suppressed interleukin-10 and tight junction protein expression in the colon. Oral administration of L sakei OK67 significantly downregulated HFD-induced expression of peroxisome proliferator-activated receptor gamma, fatty acid synthase, and tumor necrosis factor-alpha in adipose tissue. In addition, L sakei OK67 treatment strongly inhibited nuclear factor-kappaB activation in LPS-stimulated peritoneal macrophages. We report that L sakei OK67 ameliorates HFD-induced hyperglycemia and obesity by reducing inflammation and increasing the expression of colon tight junction proteins in mice. PMID- 27001280 TI - Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice. AB - The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated glucose and insulin tolerance in KD-fed diabetic mice was found, although the body weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of adipose tissue in KD mice was greater than in the other groups. The KD diet resulted in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover, the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed significant changes in several key genes such as sterol regulatory element binding protein, fibroblast growth factor 21, and peroxisome proliferator activated receptor alpha, which are all important in metabolism. In summary, KD ameliorates glucose and insulin tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and hepatic steatosis were observed, which should be considered carefully in the long-term application of KD. PMID- 27001281 TI - Modification of a traditional breakfast leads to increased satiety along with attenuated plasma increments of glucose, C-peptide, insulin, and glucose dependent insulinotropic polypeptide in humans. AB - Our hypothesis was that carbohydrate, fat, and protein contents of meals affect satiety, glucose homeostasis, and hormone secretion. The objectives of this crossover trial were to examine satiety, glycemic-insulinemic response, and plasma peptide levels in response to 2 different recommended diabetes diets with equivalent energy content. One traditional reference breakfast and one test breakfast, with lower carbohydrate and higher fat and protein content, were randomly administered to healthy volunteers (8 men, 12 women). Blood samples were collected, and satiety was scored on a visual analog scale before and 3 hours after meals. Plasma glucose was measured, and levels of C-peptide, ghrelin, glucagon, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide (GIP), insulin, plasminogen activator inhibitor-1, and adipokines were analyzed by Luminex. Greater satiety, visual analog scale, and total and delta area under the curve (P < .001), and lower glucose postprandial peak (max) and change from baseline (dmax; P < .001) were observed after test meal compared with reference meal. Postprandial increments of C-peptide, insulin, and GIP were suppressed after test meal compared with reference meal (total delta area under the curve [P = .03, .006, and .004], delta area under the curve [P = .006, .003, and .02], max [P = .01, .007, and .002], and dmax [P = .004, .008, and .007], respectively). Concentrations of other peptides were similar between meals. A lower carbohydrate and higher fat and protein content provides greater satiety and attenuation of C peptide, glucose, insulin, and GIP responses compared with the reference breakfast but does not affect adipokines, ghrelin, glucagon, glucagon-like peptide-1, and plasminogen activator inhibitor-1. PMID- 27001282 TI - Opuntia ficus-indica seed attenuates hepatic steatosis and promotes M2 macrophage polarization in high-fat diet-fed mice. AB - Opuntia ficus-indica (L.) is a popular edible plant that possesses considerable nutritional value and exhibits diverse biological actions including anti inflammatory and antidiabetic activities. In this study, we hypothesized that DWJ504, an extract of O ficus-indica seed, would ameliorate hepatic steatosis and inflammation by regulating hepatic de novo lipogenesis and macrophage polarization against experimental nonalcoholic steatohepatitis. Mice were fed a normal diet or a high-fat diet (HFD) for 10 weeks. DWJ504 (250, 500, and 1000 mg/kg) or vehicle (0.5% carboxymethyl cellulose) were orally administered for the last 4 weeks of the 10-week HFD feeding period. DWJ504 treatment remarkably attenuated HFD-induced increases in hepatic lipid content and hepatocellular damage. DWJ504 attenuated increases in sterol regulatory element-binding protein 1 and carbohydrate-responsive element-binding protein expression and a decrease in carnitine palmitoyltransferase 1A. Although DWJ504 augmented peroxisome proliferator-activated receptor alpha protein expression, it attenuated peroxisome proliferator-activated receptor gamma expression. Moreover, DWJ504 promoted hepatic M2 macrophage polarization as indicated by attenuation of the M1 marker genes and enhancement of M2 marker genes. Finally, DWJ504 attenuated expression of toll-like receptor 4, nuclear factor kappaB, tumor necrosis factor alpha, interleukin 6, TIR-domain-containing adapter-inducing interferon beta, and interferon beta levels. Our results demonstrate that DWJ504 prevented intrahepatic lipid accumulation, induced M2 macrophage polarization, and suppressed the toll-like receptor 4-mediated inflammatory signaling pathway. Thus, DWJ504 has therapeutic potential in the prevention of nonalcoholic fatty liver disease. PMID- 27001283 TI - Suppressive effects of polyozellin on TGFBIp-mediated septic responses in human endothelial cells and mice. AB - Polyozellus multiplex (Thelephoraceae) is a wild mushroom in Korea and Japan and is usually harvested in early autumn for food. Polyozellin, a major constituent of the edible mushroom P multiplex, has been known to exhibit biological activities such as antioxidative and anti-inflammatory effects. Transforming growth factor beta-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-beta. TGFBIp is released by human umbilical vein endothelial cells and functions as a mediator of experimental sepsis. We hypothesized that polyozellin could reduce TGFBIp mediated severe inflammatory responses in human endothelial cells and mice. Here, we investigated the antiseptic effects and underlying mechanisms of polyozellin against TGFBIp-mediated septic responses. Polyozellin effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses. In addition, polyozellin suppressed cecal ligation and puncture induced sepsis lethality and pulmonary injury. In conclusion, polyozellin suppressed TGFBIp-mediated and cecal ligation and puncture-induced septic responses. Therefore, polyozellin could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway. PMID- 27001284 TI - Comparison of adenoma detection rate and adenoma per colonoscopy as a quality indicator of colonoscopy. AB - BACKGROUND: Although adenoma detection rate (ADR) has been proposed as a quality indicator of colonoscopies, adenomas per colonoscopy (APC) is a promising alternative to ADR, as it reflects inspection over the entire length of the colon. This study investigated the correlation between ADR and APC, and compared the efficacy of ADR and APC based on the correlation of each with the advanced adenoma detection rate (AADR). STUDY: Two prospectively collected databases, including the 1142 subjects who underwent screening colonoscopies by 28 colonoscopists, were retrospectively reviewed. AADR1 were definded as the proportion of participants having advanced neoplasms, and AADR2 were definded as the proportion of participants having advanced neoplasms or three or more adenomas. Pearson correlation and Steiger's z-test was used to evaluate the relationship between ADR-APC, ADR-AADR and APC-AADR. RESULTS: The ADRs ranged from 16.67 to 66.67% (mean, 37.29%) and APCs ranged from 0.22 to 1.28 (mean, 0.65). The ADR and APC showed a significant correlation (R = 0.82; p < 0.001). The screening ADR was significantly correlated with AADR1/AADR2 (R = 0.60; p = 0.001 and R = 0.64; p < 0.001, respectively). APC was also significantly correlated with AADR1/AADR2 (R = 0.65; p < 0.001 and R = 0.77; p < 0.001, respectively). The correlation coefficient for APC-AADR2 was higher than ADR AADR2 (0.77 versus 0.64, p = 0.04). CONCLUSIONS: Colonoscopists' ADRs and APC were significantly correlated. Moreover, as the correlation coefficient for AADR was higher with APC than it was with ADR, APC might be a better quality indicator of colonoscopy than ADR. PMID- 27001285 TI - Symmetrical Intertriginous and Flexural Exanthema due to Bortezomib (a Proteasome Inhibitor) Given for Myeloma. PMID- 27001286 TI - Electrocatalytic activity of NiO on silicon nanowires with a carbon shell and its application in dye-sensitized solar cell counter electrodes. AB - To improve the catalytic activity of a material, it is critical to maximize the effective surface area by directly contacting the electrolyte. Nanowires are a promising building block for catalysts in electrochemical applications because of their large surface area. Nickel oxide (NiO) decoration was achieved by drop casting a nickel-dissolved solution onto vertically aligned silicon nanowire arrays with a carbon shell (SiNW/C). Based on the hybridization of the NiO and silicon nanowire arrays with a carbon shell this study aimed to achieve a synergic effect for the catalytic activity performance. This study demonstrated that the resulting nanomaterial exhibits excellent electrocatalytic activity and performs well as a counter electrode for dye-sensitized solar cells (DSSCs). The compositions of the materials were examined using X-ray diffraction, X-ray photoelectron spectroscopy, and energy dispersive spectroscopy. Their micro- and nano-structures were investigated using scanning electron microscopy and transmission electron microscopy. The electrochemical activity toward I(-)/I3(-) was examined using cyclic voltammetry and electrochemical impedance spectroscopy. The obtained peak power conversion efficiency of the DSSC based on the NiO@SiNW/C counter electrode was 9.49%, which was greater than that of the DSSC based on the Pt counter electrode. PMID- 27001287 TI - Expression changes of proteins associated with the development of preeclampsia in maternal plasma: A case-control study. AB - Defective deep placentation, involving abnormal transformation of the spiral arteries in the junctional zone of the myometrium, is known to cause significant obstetric complications, such as preeclampsia (PE), fetal growth restriction, and placental infarction leading to fetal death. Serological biomarkers to predict and diagnose PE would help antenatal care and reduce obstetric complications. To discover candidate PE biomarkers, we first performed global proteomic profiling of three pairs of plasma samples obtained from pregnant women in the early second trimester, who subsequently developed PE, and controls to identify candidate proteins that were abundant in the patients. We further evaluated the changes in the expression of PE-representing proteins in stored plasma samples of a cohort that subsequently developed PE and their matched controls by MRM-MS analysis. We identified that both complement C1s subcomponent (C1S) and protein AMBP were elevated in the plasma samples of the PE cohort before the manifestation of clinical disease. We propose that these proteins may be involved in the remodeling process of the spiral arteries even before PE manifestation. These proteins can serve as potential plasma biomarkers to predict the pregnant women having an increased risk of developing PE. PMID- 27001288 TI - Which factors make clean intermittent (self) catheterisation successful? AB - AIMS AND OBJECTIVES: To explore which factors determine successful intermittent catheterisation. BACKGROUND: Intermittent catheterisation is a safe, effective treatment and is associated with improved quality of life, although negative issues are reported. Factors which determine adherence are largely unknown. An additional qualitative study was conducted to gain insight into patient's experience with intermittent catheterisation in everyday life. DESIGN: A prospective multicentre study was conducted between March 2012-March 2013 with one year follow-up. METHODS: Patients with a variety of diagnoses referred to the outpatient clinic, >=18 years, performed catheterisation at least once a day for >=3 months were included. Data were obtained by patients' specific questionnaire Visual Analog Scale of quality of life regarding voiding problems, a questionnaire about catheterisation in daily practice, King's Health questionnaire, and a short questionnaire after one year. RESULTS: Of the 129 (72 male) patients, mean age 62 (22-86) years, seven died and 63 stopped, 32/63 (50%) due to recovered bladder function. Fifty-nine (47%) continued to perform catheterisation after one year. Forty-seven (86%) patients reported catheterisation had become part of their life or had a positive effect on their life. A weak correlation was found between increasing age and cessation of catheterisation. Visual Analogue Scale - score on quality of life improved for the total group. The King's Health questionnaire identified in the total group that the impact of the bladder problem in daily life, limitations in daily activities and negative emotions decreased over time. CONCLUSION: Adherence of successful intermittent catheterisation can be influenced negatively by increasing age. However, we think catheterisation should be considered as an option for older patients. We could not conform that if intermittent catheterisation was beneficial for the patient, it would positively influence adherence. Further prospective studies on adherence of intermittent catheterisation in larger groups need to be undertaken. RELEVANCE TO CLINICAL PRACTICE: After implementation of the national guideline in 2008, we were able to perform a multicentre study. This prospective study gives insight into patients who were undertaking intermittent catheterisation and which factors determine successful intermittent catheterisation adherence. After following the national guideline, we found no factors for additional interventions in assessment or coaching intermittent catheterisation. Post void residual volume turned out to be not a predictor for the necessity of intermittent catheterisation. A large group of patients could discontinue intermittent catheterisation during follow-up due to bladder function recovery. Although a weak correlation was found between increasing age and ceasing of catheterisation, we think the older can benefit from intermittent catheterisation. In the first period, additional support, for example given by a district nurse, may be necessary for this group to achieve better outcomes. PMID- 27001289 TI - Velocity distribution in active particles systems. AB - We derive an analytic expression for the distribution of velocities of multiple interacting active particles which we test by numerical simulations. In clear contrast with equilibrium we find that the velocities are coupled to positions. Our model shows that, even for two particles only, the individual velocities display a variance depending on the interparticle separation and the emergence of correlations between the velocities of the particles. When considering systems composed of many particles we find an analytic expression connecting the overall velocity variance to density, at the mean-field level, and to the pair distribution function valid in the limit of small noise correlation times. Finally we discuss the intriguing analogies and main differences between our effective free energy functional and the theoretical scenario proposed so far for phase-separating active particles. PMID- 27001290 TI - Characterization of flagellins isolated from a highly motile strain of Lactobacillus agilis. AB - BACKGROUND: Most lactic acid bacteria are non-motile but some of them are flagellated and exhibit motility. So far, motile lactobacilli have rarely been studied, and characteristics of their flagellins are poorly understood. In this study, a highly motile strain of Lactobacillus agilis was recruited for transcriptional analysis and characterization of its flagellins. RESULTS: Unlike another motile lactic acid bacteria of intestinal isolate, Lactobacillus ruminis, flagellar filaments of the L. agilis strain probably consist of two homologous but distinct flagellins. Glycosylation of the flagellar filaments and their resistance to heat, acid and SDS were also observed. The immunological activity of the flagellins was evaluated through the stimulation of Caco-2 cells. The results show that TLR5-stimulating activity of the protein is attenuated, likely due to an incomplete TLR5-recognition site. CONCLUSIONS: The flagella filaments of L. agilis BKN88 consist of two homologous glycosylated flagellins, which likely have an incomplete TLR5-recognition site. The characteristics of the flagellin are presumably a consequence of adaptation as a commensal microbe in the gastrointestinal tract. PMID- 27001291 TI - Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. AB - Interaction with intestinal microbes in infancy has a profound impact on health and disease in later life through programming of immune and metabolic pathways. We collected maternal faeces, placenta, amniotic fluid, colostrum, meconium and infant faeces samples from 15 mother-infant pairs in an effort to rigorously investigate prenatal and neonatal microbial transfer and gut colonisation. To ensure sterile sampling, only deliveries at full term by elective caesarean section were studied. Microbiota composition and activity assessment by conventional bacterial culture, 16S rRNA gene pyrosequencing, quantitative PCR, and denaturing gradient gel electrophoresis revealed that the placenta and amniotic fluid harbour a distinct microbiota characterised by low richness, low diversity and the predominance of Proteobacteria. Shared features between the microbiota detected in the placenta and amniotic fluid and in infant meconium suggest microbial transfer at the foeto-maternal interface. At the age of 3-4 days, the infant gut microbiota composition begins to resemble that detected in colostrum. Based on these data, we propose that the stepwise microbial gut colonisation process may be initiated already prenatally by a distinct microbiota in the placenta and amniotic fluid. The link between the mother and the offspring is continued after birth by microbes present in breast milk. PMID- 27001292 TI - Crenalkalicoccus roseus gen. nov., sp. nov., a thermophilic bacterium isolated from alkaline hot springs. AB - Two closely related thermophilic bacterial strains, designated YIM 78023T and YIM 78058, were isolated from samples collected from two alkaline hot springs in Tengchong county, Yunnan province, south-west China. The novel isolates were Gram stain-negative, non-motile, aerobic ovoid- to coccoid-shaped and non-spore forming. Strain YIM 78023T grew at 20-60 oC and pH 6.0-9.0 with optimal growth observed at 40-50 oC and pH 8.0, while strain YIM 78058 grew at 25-60 oC and pH 6.0-10.0 with optimal growth at 45-50 oC and pH 8.0. Phylogenetic analysis based on 16S rRNA gene sequences affiliated these two isolates within the family Acetobacteraceae with high sequence similarities to members of the genera Roseomonas and Belnapia (all sequence similarities <94.5 %). In addition to the above two genera, these strains also clustered with the genera Craurococcus and Paracraurococcus (having sequence similarities <93.3 %) in the phylogenetic tree, but with a distinct lineage within the family Acetobacteraceae. The major ubiquinone was Q-10 and the major fatty acids observed were C18:1omega7c, summed feature 4 and C16:0. The genomic DNA G+C contents observed for strains YIM 78023T and YIM 78058 were 74.3 and 74.0 mol%, respectively. Morphological, phylogenetic and chemotaxonomic results suggest that strains YIM 78023T and YIM 78058 are representatives of a novel species of a new genus within the family Acetobacteraceae, for which the name Crenalkalicoccus roseus gen. nov., sp. nov. is proposed. The type strain of Crenalkalicoccus roseus is YIM 78023T (=JCM 19657T=KACC 17825T). PMID- 27001293 TI - Outcome of cervix uteri cancer patients: Clinical treatment results and toxicity profile in a retrospective study from Saudi Arabia. AB - AIM: This study evaluated the survival outcome, pattern of failure and prognostic factors in cervix uteri cancer patients. METHODS: We reviewed the data of 60 patients with stages IB-IVA cancer who were treated between January 2004 and December 2010. RESULTS: Most patients (n = 50; 83%) had squamous cell carcinoma. Stage IIB was the most common presentation (n = 41; 68%). Forty-seven patients (78%) received Cisplatin concurrent with radiotherapy (CRT). The 2- and 4-year overall survival (OS) was 82% and 79%, respectively. Prolongation of the overall treatment time (OAT) for greater than 56 days, advanced stage and pretreatment hemoglobin (Hb) levels (<10 g/dL) negatively predicted OS (P = 0.039, P = 0.044 and P = 0.008, respectively). The 2- and 4-year disease-free survival (DFS) rates were 80% and 69%, respectively. Vaginal infiltration and brachytherapy (orthogonal versus CT-based planning) were significant factors for the prediction of relapse (P = 0.048 and P = 0.049, respectively). The 2- and 4-year loco regional control (LRC) rates were 78% and 70%, respectively, and the distant metastasis-free survival (DMFS) rates were 82% and 79%, respectively. Vaginal infiltration was the only negative predictive factor for LRC (P = 0.045), and pathological tumor grade was the only factor indicative of distant metastases (P = 0.037). Grade 3 or 4 late rectal reactions were reported in two patients (3%), and no patients developed grade 3 or 4 urinary reactions. CONCLUSION: The treatment results in our cervix uteri cancer patients and the prognostic factors are comparable to those of previous reports. Orthogonal brachytherapy planning and vaginal infiltration negatively predicted relapse. PMID- 27001294 TI - Triage for Out-of-Office Blood Pressure. PMID- 27001295 TI - Unattended Blood Pressure Measurements in the Systolic Blood Pressure Intervention Trial: Implications for Entry and Achieved Blood Pressure Values Compared With Other Trials. PMID- 27001296 TI - Adventures in the Adventitia. PMID- 27001297 TI - Angiotensin II Stimulation of Cardiac Hypertrophy and Functional Decompensation in Osteoprotegerin-Deficient Mice. AB - Circulating and myocardial expressions of receptor activator of nuclear factor kappab ligand and osteoprotegerin are activated in heart failure; however, it remains to be determined their pathophysiological roles on left ventricular structure and function in interaction with renin-angiotensin system. We conducted experiments using 8-week-old osteoprotegerin(-/-) mice and receptor activator of nuclear factor-kappab ligand-transgenic mice to assess whether they affect the angiotensin II-induced left ventricular remodeling. Subcutaneous infusion of angiotensin II to osteoprotegerin(-/-) mice progressed the eccentric hypertrophy, resulting in left ventricular systolic dysfunction for 28 days, and this was comparable with wild-type mice, showing concentric hypertrophy, irrespective of equivalent elevation of systolic blood pressure. The structural alteration was associated with reduced interstitial fibrosis, decreased procollagen alpha1 and syndecan-1 expressions, and the increased number of apoptotic cells in the left ventricle, compared with wild-type mice. In contrast, angiotensin II infusion to the receptor activator of nuclear factor-kappab ligand-transgenic mice revealed the concentric hypertrophy with preserved systolic contractile function. Intraperitoneal administration of human recombinant osteoprotegerin, but not subcutaneous injection of anti-receptor activator of nuclear factor-kappab ligand antibody, to the angiotensin II-infused osteoprotegerin(-/-) mice for 28 days ameliorated the progression of heart failure without affecting systolic blood pressure. These results underscore the biological activity of osteoprotegerin in preserving myocardial structure and function during the angiotensin II-induced cardiac hypertrophy, independent of receptor activator of nuclear factor-kappab ligand activity. In addition, the antiapoptotic and profibrotic actions of osteoprotegerin that emerged from our data might be involved in the mechanisms. PMID- 27001298 TI - Excessive Adventitial Remodeling Leads to Early Aortic Maladaptation in Angiotensin-Induced Hypertension. AB - The primary function of central arteries is to store elastic energy during systole and to use it to sustain blood flow during diastole. Arterial stiffening compromises this normal mechanical function and adversely affects end organs, such as the brain, heart, and kidneys. Using an angiotensin II infusion model of hypertension in wild-type mice, we show that the thoracic aorta exhibits a dramatic loss of energy storage within 2 weeks that persists for at least 4 weeks. This diminished mechanical functionality results from increased structural stiffening as a result of an excessive accumulation of adventitial collagen, not a change in the intrinsic stiffness of the wall. A detailed analysis of the transmural biaxial wall stress suggests that the exuberant production of collagen results more from an inflammatory response than from a mechano-adaptation, hence reinforcing the need to control inflammation, not just blood pressure. Although most clinical assessments of arterial stiffening focus on intimal-medial thickening, these results suggest a need to measure and control the highly active and important adventitia. PMID- 27001299 TI - Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP): Derivation and Validation of a Tool to Improve the Accuracy of Blood Pressure Measurement in Clinical Practice. AB - Patients often have lower (white coat effect) or higher (masked effect) ambulatory/home blood pressure readings compared with clinic measurements, resulting in misdiagnosis of hypertension. The present study assessed whether blood pressure and patient characteristics from a single clinic visit can accurately predict the difference between ambulatory/home and clinic blood pressure readings (the home-clinic difference). A linear regression model predicting the home-clinic blood pressure difference was derived in 2 data sets measuring automated clinic and ambulatory/home blood pressure (n=991) using candidate predictors identified from a literature review. The model was validated in 4 further data sets (n=1172) using area under the receiver operator characteristic curve analysis. A masked effect was associated with male sex, a positive clinic blood pressure change (difference between consecutive measurements during a single visit), and a diagnosis of hypertension. Increasing age, clinic blood pressure level, and pulse pressure were associated with a white coat effect. The model showed good calibration across data sets (Pearson correlation, 0.48-0.80) and performed well-predicting ambulatory hypertension (area under the receiver operator characteristic curve, 0.75; 95% confidence interval, 0.72-0.79 [systolic]; 0.87; 0.85-0.89 [diastolic]). Used as a triaging tool for ambulatory monitoring, the model improved classification of a patient's blood pressure status compared with other guideline recommended approaches (93% [92% to 95%] classified correctly; United States, 73% [70% to 75%]; Canada, 74% [71% to 77%]; United Kingdom, 78% [76% to 81%]). This study demonstrates that patient characteristics from a single clinic visit can accurately predict a patient's ambulatory blood pressure. Usage of this prediction tool for triaging of ambulatory monitoring could result in more accurate diagnosis of hypertension and hence more appropriate treatment. PMID- 27001300 TI - Role of VEGF-A in angiogenesis promoted by umbilical cord-derived mesenchymal stromal/stem cells: in vitro study. AB - BACKGROUND: Mesenchymal stromal/stem cells derived from human umbilical cord (UC MSCs) uniquely combine properties of embryonic and postnatal MSCs and may be the most acceptable, safe, and effective source for allogeneic cell therapy e.g. for therapeutic angiogenesis. In this report we describe pro-angiogenic properties of UC-MSCs as manifested in vitro. METHODS: UC-MSCs were isolated from human Wharton's jelly by enzymatic digestion. Presence of soluble forms of VEGF-A in UC MSC-conditioned media was measured by ELISA. Effects of the conditioned media on human umbilical vein-derived endothelial EA.hy926 cells proliferation were measured by MTT-assay; changes in cell motility and directed migration were assessed by scratch wound healing and transwell chamber migration assays. Angiogenesis was modeled in vitro as tube formation on basement membrane matrix. Progressive differentiation of MSCs to endothelioid progeny was assessed by CD31 immunostaining. RESULTS: Although no detectable quantities of soluble VEGF-A were produced by UC-MSCs, the culture medium, conditioned by the UC-MSCs, effectively stimulated proliferation, motility, and directed migration of EA.hy926 cells. In 2D culture, UC-MSCs were able to acquire CD31(+) endothelial cell-like phenotype when stimulated by EA.hy926-conditioned media supplemented with VEGF-A165. UC MSCs were capable of forming unstable 2D tubular networks either by themselves or in combinations with EA.hy926 cells. Active spontaneous sprouting from cell clusters, resulting from disassembling of such networks, was observed only in the mixed cultures, not in pure UC-MSC cultures. In 3D mode of sprouting experimentation, structural support of newly formed capillary-like structures was provided by UC-MSCs that acquired the CD31(+) phenotype in the absence of exogenous VEGF-A. CONCLUSION: These data suggest that a VEGF-A-independent paracrine mechanism and at least partially VEGF-A-independent differentiation mechanism are involved in the pro-angiogenic activity of UC-MSCs. PMID- 27001302 TI - The Acceleration of Immigrant Unhealthy Assimilation. AB - It is well known that immigrants tend to be healthier than US natives and that this advantage erodes with time spent in the USA. However, we know less about the heterogeneity of these trajectories among arrival cohorts. Recent studies have shown that later arrival cohorts of immigrants have lower entry wages and experience less economic assimilation. In this paper, we investigate whether similar cohort effects can be observed in the weight assimilation of immigrants in the USA. Focusing on obesity, we show that more recent immigrant cohorts arrive with higher obesity rates and experience a faster 'unhealthy assimilation' in terms of weight gain. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001301 TI - Abscisic acid transcriptomic signaling varies with grapevine organ. AB - BACKGROUND: Abscisic acid (ABA) regulates various developmental processes and stress responses over both short (i.e. hours or days) and longer (i.e. months or seasons) time frames. To elucidate the transcriptional regulation of early responses of grapevine (Vitis vinifera) responding to ABA, different organs of grape (berries, shoot tips, leaves, roots and cell cultures) were treated with 10 MUM (S)-(+)-ABA for 2 h. NimbleGen whole genome microarrays of Vitis vinifera were used to determine the effects of ABA on organ-specific mRNA expression patterns. RESULTS: Transcriptomic analysis revealed 839 genes whose transcript abundances varied significantly in a specific organ in response to ABA treatment. No single gene exhibited the same changes in transcript abundance across all organs in response to ABA. The biochemical pathways affected by ABA were identified using the Cytoscape program with the BiNGO plug-in software. The results indicated that these 839 genes were involved in several biological processes such as flavonoid metabolism, response to reactive oxygen species, response to light, and response to temperature stimulus. ABA affected ion and water transporters, particularly in the root. The protein amino acid phosphorylation process was significantly overrepresented in shoot tips and roots treated with ABA. ABA affected mRNA abundance of genes (CYP707As, UGTs, and PP2Cs) associated with ABA degradation, conjugation, and the ABA signaling pathway. ABA also significantly affected the expression of several transcription factors (e.g. AP2/ERF, MYC/MYB, and bZIP/AREB). The greatest number of significantly differentially expressed genes was observed in the roots followed by cell cultures, leaves, berries, and shoot tips, respectively. Each organ had a unique set of gene responses to ABA. CONCLUSIONS: This study examined the short term effects of ABA on different organs of grapevine. The responses of each organ were unique indicating that ABA signaling varies with the organ. Understanding the ABA responses in an organ-specific manner is crucial to fully understand hormone action and plant responses to water deficit. PMID- 27001303 TI - A cluster of salivirus A1 (Picornaviridae) infections in newborn babies with acute gastroenteritis in a neonatal hospital unit in Hungary. AB - Salivirus (family Picornaviridae) may be associated with acute gastroenteritis in humans, but there have been no reports of salivirus outbreaks. Salivirus A1 infection with faecal virus concentrations of 2.1-2.6 * 10(9)/g were identified retrospectively in newborn babies, between the ages of 1.5 and 5 days, with apparent clinical symptoms of diarrhea (100 %), fever (40 %), vomiting (40 %), and loss of appetite (40 %) in a neonatal hospital unit in Hungary in July 2013. The complete genome sequence of the salivirus (including the 5'-terminal end) was determined. Salivirus mono-infection may be associated with gastroenteritis in babies who are a few days old. Salivirus testing should be done in public health laboratories in gastroenteritis outbreaks with unknown etiology. PMID- 27001304 TI - Complete genome sequence of Xishuangbanna flavivirus, a novel mosquito-specific flavivirus from China. AB - A new flavivirus, Xishuangbanna flavivirus (XFV), infecting Aedes albopictus mosquitoes in Yunnan Province, China, was isolated and sequenced. The single stranded RNA genome of 10,884 nt contained two open reading frames (ORFs) encoding the polyprotein and FIFO. The genome had a maximum nucleotide sequence identity of 65 % to Parramatta River virus with coverage of only 27 %. Phylogenetic analysis suggested that this virus is most closely related to recognized classical insect-specific flaviviruses (cISF) and most likely has a similar host range. Sequence comparisons and phylogenetic analysis demonstrated that XFV is a new member of the genus Flavivirus. PMID- 27001305 TI - Detection of West Nile virus and tick-borne encephalitis virus in birds in Slovakia, using a universal primer set. AB - West Nile virus (WNV) is a mosquito-borne neurotropic pathogen that presents a major public health concern. Information on WNV prevalence and circulation in Slovakia is insufficient. Oral and cloacal swabs and bird brain samples were tested for flavivirus RNA by RT-PCR using newly designed generic primers. The species designation was confirmed by sequencing. WNV was detected in swab and brain samples, whereas one brain sample was positive for tick-borne encephalitis virus (TBEV). The WNV sequences clustered with lineages 1 and 2. These results confirm the circulation of WNV in birds in Slovakia and emphasize the risk of infection of humans and horses. PMID- 27001306 TI - Response to Sildenafil in a Patient With Coexisting Post-Liver Transplant Portopulmonary Hypertension and Hepatopulmonary Syndrome. AB - Hepatopulmonary syndrome and portopulmonary hypertension are complications of portal hypertension with opposing mechanisms that can coexist. Moderate portopulmonary hypertension, which is a contraindication to a liver transplant, must be managed with pulmonary vasodilators to normalize pulmonary arterial pressures before a transplant listing. Concomitant hepatopulmonary syndrome complicates the management of portopulmonary hypertension, as pulmonary vasodilators can theoretically exacerbate the intrapulmonary dilatation believed to cause hepatopulmonary syndrome. We describe a case of a post-liver transplant patient with concomitant hepatopulmonary syndrome and portopulmonary hypertension safely treated with sildenafil. PMID- 27001308 TI - Evaluating Effects of Hypomorphic Thoc1 Alleles on Embryonic Development in Rb1 Null Mice. AB - The Rb1 tumor suppressor protein is a molecular adaptor that physically links transcription factors like E2f with various proteins acting on DNA or RNA to repress gene expression. Loss of Rb1 liberates E2f to activate the expression of genes mediating resulting phenotypes. Most Rb1 binding proteins, including E2f, interact through carboxyl-terminal protein interaction domains, but genetic evidence suggests that an amino-terminal protein interaction domain is also important. One protein that binds Rb1 through the amino-terminal domain is encoded by Thoc1, a required component of the THO ribonucleoprotein complex important for RNA processing and transport. The physiological relevance of this interaction is unknown. Here we tested whether Thoc1 mediates effects of Rb1 loss on mouse embryonic development. We found that Thoc1 deficiency delays embryo death, and this delay correlates with reduced apoptosis in the brain. E2f protein levels are reduced in Rb1:Thoc1-deficient brain tissue. Expression of apoptotic regulatory genes regulated by E2f, like Apaf1 and Bak1, is also reduced. These observations suggest that Thoc1 is required to support increased expression of E2f and apoptotic regulatory genes that trigger apoptosis upon Rb1 loss. These findings implicate Rb1 in the regulation of the THO ribonucleoprotein complex. PMID- 27001309 TI - Evans syndrome secondary to chronic lymphocytic leukaemia: presentation, treatment, and outcome. AB - Evans syndrome (ES) is defined by the combination (either simultaneous or sequential) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA). When related to secondary conditions, ES may arise in patients with chronic lymphocytic leukaemia (CLL), which is frequently associated to autoimmune cytopenias (AIC). We analysed 25 patients with ES secondary to CLL, which were identified from a large series of consecutive patients with CLL, diagnosed and followed up in two institutions. They represented 2.9 % of the whole series. Thirteen patients presented with concurrent ITP and AIHA (simultaneous ES), while others developed the two AIC sequentially. Occurrence of ES was associated with unfavourable biological prognostic factors like ZAP-70 expression, unmutated immunoglobulin heavy chain variable region gene status, 17-p13 deletion and TP53 gene mutations. Of note, the majority of patients with ES (66 %) had stereotyped B cell receptor configuration. Most patients had short-lasting remissions and required second-line treatments to control the autoimmune manifestations of ES. Patients with ES were associated with inferior survival compared to patients not developing AIC, especially when ES developed early in the course of CLL, although the reduced survival was not confirmed by multivariate analysis. In conclusion, ES secondary to CLL is a difficult-to-treat complication, characterised by adverse biological features and clinical outcome. PMID- 27001307 TI - Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction. AB - Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor kappaB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction. PMID- 27001310 TI - Simultaneous determination of tricarboxylic acid cycle metabolites by high performance liquid chromatography with ultraviolet detection. AB - Here we describe a simple high-performance liquid chromatography (HPLC) procedure for the simultaneous detection and quantitation in standard solutions of 13 important metabolites of cellular energy metabolism, including 9 tricarboxylic acid (TCA) cycle components and 4 additional metabolites. The metabolites are detected by their absorbance at 210 nm. The procedure does not require prior derivatization, and an analysis can be carried out at ambient temperature within 15 min. The significance of the current work is that the current HPLC procedure should motivate the development of simplified TCA cycle enzyme assays, isotopomer analysis, and determination of selected TCA metabolite levels in plasma/tissues. PMID- 27001311 TI - An Innovative Use of Case Conference to Teach Future Educators in Addiction Psychiatry. AB - Objective An innovative course was developed for fellows enrolled in the Yale School of Medicine Addiction Psychiatry program to educate them in key principles of adult learning, apply these principles in a case conference presentation, and to improve skills in providing and receiving feedback. Methods An initial training module on educational skills was followed by individual mentorship to prepare a case presentation. A feedback module provided space to learn and practice skills in feedback delivery. Results The program showed positive results and improved confidence levels of the participants in presenting and providing/receiving feedback. Conclusions Implementing a course designed to improve teaching and feedback skills is feasible in a 1-year Addiction Psychiatry fellowship. PMID- 27001312 TI - B7-H4(B7x)-Mediated Cross-talk between Glioma-Initiating Cells and Macrophages via the IL6/JAK/STAT3 Pathway Lead to Poor Prognosis in Glioma Patients. AB - PURPOSE: The objective of this study was to evaluate clinical significance and immunosuppressive mechanisms of B7-H4 (B7x/B7S1), a B7 family member, in glioma. EXPERIMENTAL DESIGN: B7-H4 levels in glioma tissue/cerebral spinal fluid (CSF) were compared between different grades of glioma patients. Survival data were analyzed with Kaplan-Meier to determine the prognostic value of B7-H4. Cytokines from CD133(+) cells to stimulate the expression of B7-H4 on human macrophages (Mphis) were investigated by FACS, neutralizing antibodies, and Transwell chemotaxis assay. shRNA, reporter vector, and chromatin immunoprecipitation were used to determine the binding of STAT3 to the B7-H4 promoter. The function of B7 H4(+) Mphis in vitro was evaluated through phagocytosis, T-cell proliferation/apoptosis, and cytokine production as well as in the xenografted model for in vivo analysis. RESULTS: We found that B7-H4 expression in tumors was associated with prognosis of human glioblastoma and correlated directly with malignant grades. Mechanistically, glioma initiating CD133(+) cells and Mphis/microglia cointeraction activated expression of B7-H4 via IL6 and IL10 in both tumor cells and microenvironment supporting cells. IL6-activated STAT3 bound to the promoter of B7-H4 gene and enhanced B7-H4 expression. Furthermore, CD133(+) cells mediated immunosuppression through B7-H4 expression on Mphis/microglia by silencing of B7-H4 expression on these cells, which led to increased microenvironment T-cell function and tumor regression in the xenograft glioma mouse model. CONCLUSIONS: We have identified B7-H4 activation on Mphis/microglia in the microenvironment of gliomas as an important immunosuppressive event blocking effective T-cell immune responses. Clin Cancer Res; 22(11); 2778-90. (c)2016 AACR. PMID- 27001313 TI - Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays. AB - PURPOSE: Rational development of targeted MET inhibitors for cancer treatment requires a quantitative understanding of target pharmacodynamics, including molecular target engagement, mechanism of action, and duration of effect. EXPERIMENTAL DESIGN: Sandwich immunoassays and specimen handling procedures were developed and validated for quantifying full-length MET and its key phosphospecies (pMET) in core tumor biopsies. MET was captured using an antibody to the extracellular domain and then probed using antibodies to its C-terminus (full-length) and epitopes containing pY1234/1235, pY1235, and pY1356. Using pMET:MET ratios as assay endpoints, MET inhibitor pharmacodynamics were characterized in MET-amplified and -compensated (VEGFR blockade) models. RESULTS: By limiting cold ischemia time to less than two minutes, the pharmacodynamic effects of the MET inhibitors PHA665752 and PF02341066 (crizotinib) were quantifiable using core needle biopsies of human gastric carcinoma xenografts (GTL-16 and SNU5). One dose decreased pY1234/1235 MET:MET, pY1235-MET:MET, and pY1356-MET:MET ratios by 60% to 80% within 4 hours, but this effect was not fully sustained despite continued daily dosing. VEGFR blockade by pazopanib increased pY1235-MET:MET and pY1356-MET:MET ratios, which was reversed by tivantinib. Full length MET was quantifiable in 5 of 5 core needle samples obtained from a resected hereditary papillary renal carcinoma, but the levels of pMET species were near the assay lower limit of quantitation. CONCLUSIONS: These validated immunoassays for pharmacodynamic biomarkers of MET signaling are suitable for studying MET responses in amplified cancers as well as compensatory responses to VEGFR blockade. Incorporating pharmacodynamic biomarker studies into clinical trials of MET inhibitors could provide critical proof of mechanism and proof of concept for the field. Clin Cancer Res; 22(14); 3683-94. (c)2016 AACR. PMID- 27001314 TI - Women's Work Pathways Across the Life Course. AB - Despite numerous changes in women's employment in the latter half of the twentieth century, women's employment continues to be uneven and stalled. Drawing from data on women's weekly work hours in the National Longitudinal Survey of Youth (NLSY79), we identify significant inequality in women's labor force experiences across adulthood. We find two pathways of stable full-time work for women, three pathways of part-time employment, and a pathway of unpaid labor. A majority of women follow one of the two full-time work pathways, while fewer than 10% follow a pathway of unpaid labor. Our findings provide evidence of the lasting influence of work-family conflict and early socioeconomic advantages and disadvantages on women's work pathways. Indeed, race, poverty, educational attainment, and early family characteristics significantly shaped women's work careers. Work-family opportunities and constraints also were related to women's work hours, as were a woman's gendered beliefs and expectations. We conclude that women's employment pathways are a product of both their resources and changing social environment as well as individual agency. Significantly, we point to social stratification, gender ideologies, and work-family constraints, all working in concert, as key explanations for how women are "tracked" onto work pathways from an early age. PMID- 27001315 TI - The long non-coding RNA FMR4 promotes proliferation of human neural precursor cells and epigenetic regulation of gene expression in trans. AB - Triplet repeat expansions in the Fragile X mental retardation 1 (FMR1) gene cause either intellectual disability and autism, or adult-onset neurodegeneration, with poorly understood variability in presentation. Previous studies have identified several long noncoding RNAs (lncRNAs) at the FMR1 locus, including FMR4. Similarly to FMR1, FMR4 is silenced by large-repeat expansions that result in enrichment of DNA and histone methylation within the shared promoter and repeat sequence, suggesting a possible role for this noncoding RNA in the pathophysiology of Fragile X. We therefore assessed the functional role of FMR4 to gain further insight into the molecular processes in Fragile X-associated disorders. Previous work showed that FMR4 does not exhibit cis-regulation of FMR1. Here, we found that FMR4 is a chromatin-associated transcript and, using genome-wide chromatin immunoprecipitation experiments, showed that FMR4 alters the chromatin state and the expression of several hundred genes in trans. Among the genes regulated by FMR4, we found enrichment for those involved in neural development and cellular proliferation. S-phase marker assays further demonstrated that FMR4 may promote cellular proliferation, rather than differentiation, of human neural precursor cells (hNPCs). By establishing this novel function for FMR4 in hNPCs, we lend support to existing evidence of the epigenetic involvement of lncRNA in nervous system development, and increase our understanding of the complex pathogenesis underlying neurological disorders associated with FMR1 repeat expansions. PMID- 27001316 TI - Psychodermatologic Effects of Atopic Dermatitis and Acne: A Review on Self-Esteem and Identity. AB - Atopic dermatitis (AD) and acne vulgaris are among the most-prevalent skin diseases in children. Both have been well documented in the literature to have significant negative effects on quality of life. Herein, we discuss the results of a comprehensive literature review aimed at assessing the impact of acne and AD on self-esteem and identity. We highlight clinical tools for their assessment and offer coping strategies for patients and families. Multiple factors including relationships with parents and classmates, sports participation, and the sex of the patient contribute to the development of self-esteem and identity in individuals with AD and acne. Atopic dermatitis was found to have significant behavioral effects on children, ultimately resulting in a lack of opportunity to develop proper coping. AD had a more-prominent role in identity formation and gender roles in girls. Acne vulgaris was found to have a more direct effect on self-esteem, self-confidence and identity, especially in girls. The Cutaneous Body Image Scale is reviewed and offered as an easy and reliable tool to evaluate a patient's mental perception of the appearance of their skin. Coping strategies that may be offered to patients and families include empowerment and cognitive adaptation. PMID- 27001319 TI - Patient Perspectives: What is Psoriasis? PMID- 27001318 TI - Cutaneous Lupus Erythematosus in Children: Experience from a Tertiary Care Pediatric Dermatology Clinic. AB - BACKGROUND/OBJECTIVES: The manifestations of cutaneous lupus erythematosus (CLE) and their relevance to systemic disease are well characterized in adults, but data are limited in children. The objective of the current study was to examine the spectrum of CLE and its relationship to systemic disease in children from a tertiary care pediatric dermatology clinic. MATERIALS AND METHODS: An analysis of 26 children with CLE registered consecutively over 14 years was performed. RESULTS: Ninety-six percent of the patients were of Arab ethnicity. They included seven (27%) cases with neonatal lupus erythematosus (LE) (71% females and 29% males). Of the other 19 children with CLE, 95% were female. The mean and median age at diagnosis was 11 years. Eighty-nine percent of the patients fulfilled the criteria for systemic LE. All patients had LE-specific lesions and 83% had LE nonspecific manifestations. Atypical initial presentations were recorded in 28% of the patients, and 22% of the patients had the rare LE variants. Of the LE specific manifestations, acute CLE was seen in 83%, subacute in 44%, and chronic in 22%. Autoimmune associations were recorded in 44% and a positive family history of autoimmune diseases in 61%. CONCLUSION: This study highlights a striking female predominance, higher risk of systemic disease in children presenting with CLE, higher prevalence of atypical presentation and rare CLE variants, and underrepresentation of discoid LE in children and signifies the need for more surveys to delineate the spectrum of pediatric CLE in different parts of the world. PMID- 27001317 TI - Effects of a New Emollient-Based Treatment on Skin Microflora Balance and Barrier Function in Children with Mild Atopic Dermatitis. AB - BACKGROUND/OBJECTIVES: The use of emollients is widely recommended for the management of atopic dermatitis (AD), especially between flares. An imbalance of skin microflora is suspected of playing a key role in exacerbations of AD. Our aim was to evaluate the effect of a new emollient balm on clinical parameters (SCORing Atopic Dermatitis [SCORAD], xerosis, pruritus), skin barrier function (transepidermal water loss and loricrin, filaggrin, corneodesmosin, and involucrin expression], skin microflora biodiversity, and Staphylococcus aureus and Staphylococcus epidermidis balance in children with mild AD. METHODS: Fifty four children (1-4 yrs old) were enrolled in this randomized, controlled study. Subjects applied a hygiene product and the emollient balm (emollient group, n = 28) or the hygiene product only (control group, n = 26) twice a day for 28 days. RESULTS: We found improvement in favor of the emollient group in SCORAD (p < 0.001), pruritus (p = 0.06), and xerosis (p = 0.06) after 28 days of application. Moreover, transepidermal water loss decreased in the emollient group by 34% (p = 0.06) and involucrin expression by 37% (p = 0.001) at day 28 from baseline in association with improvement in barrier function, whereas other barrier-specific proteins did not vary. S. aureus increased significantly in the control group only (6.5 times, p = 0.01), whereas S. epidermidis remained stable in both groups. The Shannon index (H' = 2.3) did not vary with treatment in either group. CONCLUSION: Twice-daily application of a new emollient balm in children with mild AD protected the skin from S. aureus proliferation and preserved microflora biodiversity. PMID- 27001320 TI - A Facial Rash in an Infant. PMID- 27001321 TI - Verrucous Plaque in a Healthy Teen. PMID- 27001322 TI - Purple-Grey Indurations with Linear and Arcuate Scarring on a Neonate. PMID- 27001323 TI - A 17-Year-Old Boy with a Fungating and Ulcerative Plaque on the Chest. PMID- 27001324 TI - Doing Our Part to Reduce Medical Costs. PMID- 27001325 TI - Management of Pediatric Psoriasis: What's True, What's Left to Do? PMID- 27001326 TI - Herbal Remedy for Lymphatic Malformations: Will This Join Our Treatment Armamentarium? PMID- 27001327 TI - Managing Molluscum with Imiquimod: Ignoring the Evidence. PMID- 27001328 TI - Chikungunya: What We Need to Know. PMID- 27001329 TI - Recurrent Aphthous Stomatitis As a Marker of Celiac Disease in Children. PMID- 27001330 TI - The "Jewelry Addict": Allergic Contact Dermatitis from Repetitive Multiple Children's Jewelry Exposures. AB - A 9-year-old girl with atopic dermatitis developed persistent plaques on the lips, hands, and fingers that were unresponsive to topical steroids. Her mother reported that she was "addicted" to costume jewelry and developed rashes in reaction to a number of adornments, ranging from rubber bracelets to costume metal jewelry and belt buckles. A careful history of jewelry exposures was taken and patch testing was performed to identify allergenic sources. Patch testing revealed allergy to nickel, gold, and thiuram mix. The case illustrates the importance of investigating a range of different types of allergens when evaluating for jewelry sensitivity in children with frequent use of accessories, including rubber jewelry, plastics, dyed yarns, beads, metals, and ceramics. This article provides an overview of jewelry allergies and the potential allergens requiring screening. PMID- 27001331 TI - Hair Follicle Nevus Located on the Chin of an Infant: Case Report and Review of Literature. AB - Hair follicle nevi are rare, benign, congenital hamartomas that usually occur in the distribution of the first brachial arch. Histopathologically, the distinction between hair follicle nevus, trichofolliculoma, and accessory tragus has recently come into question, and it may be that they are all on a spectrum of the same condition. We report the case of a 7-day-old boy who presented with a "tag"-like lesion on his midline chin that had been present since birth. Biopsy of the lesion proved it to be a hair follicle nevus. PMID- 27001332 TI - Association Between Discoid Lupus Erythematosus and Chronic Granulomatous Disease -Report of Two Cases and Review of the Literature. AB - Discoid lupus erythematosus (DLE) is known to be associated with chronic granulomatous disease (CGD), but most DLE occurs in female carriers of X-linked CGD, with few reports of these lesions in CGD-affected individuals--this observation is unexplained. We describe two cases of DLE-like lesions in boys with CGD: one boy with partial neutrophil function and another whose lesions were related to voriconazole use. Reviewing other previously reported cases, we conclude that the risk of developing DLE-like lesions appears to be greater primarily in two subsets of the population with CGD: those with partial neutrophil function and those with near-absent neutrophil function in whom there is a second trigger. In light of recent literature on the role of neutrophils in lupus pathogenesis, we propose that pathogenesis of DLE in CGD may be related to NETosis, neutrophil dysfunction and a deficiency of reactive oxygen species, which medications such as voriconazole also influence. PMID- 27001333 TI - Spitz Nevus: A Rare Lesion of the Oral Cavity. AB - Pigmented mucosal lesions represent a group of rare entities with different etiopathogenetic origins, histopathologic features, dermoscopic appearances, and clinical course. Solitary pigmented lesions of melanocytic origin are uncommon in the oral mucosa, and intraoral occurrence of Spitz nevus is very rare. Here we present a case of Spitz nevus occurring on the hard palate of a 26-month-old boy. PMID- 27001334 TI - Drug Reaction with Eosinophilia and Systemic Symptoms in Children: A Prospective Study. AB - Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction that can affect any age group. We carried out a prospective study of the clinicoepidemiologic aspects of DRESS in children. We prospectively studied all patients ages 12 years and younger admitted to the departments of pediatrics and dermatology at a tertiary care hospital over a 3-year period with probable or definite DRESS, defined based on the RegiSCAR scoring system. A total of 11 patients were studied. Lamotrigine (four patients) and pencillins (three patients) were the most common offending drugs. Not adhering to the standard guidelines of introduction and gradual titration of lamotrigine to therapeutic dose may have increased the chance of lamotrigine-induced DRESS. A short latent period between the onset of drug intake and drug reaction was noted in DRESS induced by antibiotics. PMID- 27001335 TI - Port-Wine Stain-Like Presentation of a Tufted Angioma on the Face. AB - Tufted angioma is an uncommon benign vascular tumor that typically is noted during infancy or childhood, with variable clinical presentation. We report the case of an infant with a tufted angioma initially presenting as a port-wine stain like patch of the left cheek. PMID- 27001336 TI - Delayed-Onset Sclerema Neonatorum in a Critically Ill Premature Infant. AB - Sclerema neonatorum is extremely rare in the 21st century. We report a premature infant managed in a neonatal intensive care unit with delayed development of sclerema neonatorum. PMID- 27001337 TI - Subungual Posttraumatic Ectopic Nail. AB - Ectopic nail is defined as the malformation of nail tissue in a location other than the usual nail unit. We present a 12-year-old boy with a single dystrophic thumb nail after an injury. The nail was observed under the original nail and it is linked to the original nail plate by longitudinal bridge formation with parallel growth. According to these clinical findings, the diagnosis of subungual posttraumatic ectopic nail was made. PMID- 27001338 TI - Syringomas Accentuated on the Upper Lip. AB - An 8-year-old boy presented with small, skin-colored papules of 9-months duration on the upper lip. Results of the histopathologic examination were consistent with syringoma. To the best of our knowledge, this is the first case report of syringoma of the mustache area of a child. PMID- 27001339 TI - Anti-Tumor Necrosis Factor alpha-Related Psoriatic Lesions in Children with Inflammatory Bowel Disease: Case Report and Systematic Literature Review. AB - We report a child with Crohn's disease and infliximab-induced guttate psoriasis. We also performed a systematic literature review on this intriguing paradoxical phenomenon in children with inflammatory bowel disease. PMID- 27001340 TI - UniBic: Sequential row-based biclustering algorithm for analysis of gene expression data. AB - Biclustering algorithms, which aim to provide an effective and efficient way to analyze gene expression data by finding a group of genes with trend-preserving expression patterns under certain conditions, have been widely developed since Morgan et al. pioneered a work about partitioning a data matrix into submatrices with approximately constant values. However, the identification of general trend preserving biclusters which are the most meaningful substructures hidden in gene expression data remains a highly challenging problem. We found an elementary method by which biologically meaningful trend-preserving biclusters can be readily identified from noisy and complex large data. The basic idea is to apply the longest common subsequence (LCS) framework to selected pairs of rows in an index matrix derived from an input data matrix to locate a seed for each bicluster to be identified. We tested it on synthetic and real datasets and compared its performance with currently competitive biclustering tools. We found that the new algorithm, named UniBic, outperformed all previous biclustering algorithms in terms of commonly used evaluation scenarios except for BicSPAM on narrow biclusters. The latter was somewhat better at finding narrow biclusters, the task for which it was specifically designed. PMID- 27001341 TI - Selection of new objects by onset capture and visual marking. AB - Visual search is easier after looking at some distractors in advance because previewed distractors are excluded from the search (preview benefit). A dominant explanation for preview benefit is that it occurs because of the inhibition of old objects (visual marking). However, another view claims that preview benefit simply reflects automatic attentional orienting to new objects (onset capture). To address the question of whether visual marking plays any role in addition to onset capture, we compared the search performance for a target that always appeared as a new item ("marking" condition) with the performance for a target that appeared equally as a new or old item ("capture" condition). When items were presented at random positions in an invisible matrix, the slope in the "marking" condition was shallower than that in the "capture" condition, favoring the involvement of visual marking (Experiments 1 and 2). In contrast, no difference in slope was found among the search conditions regardless of changes in old items when items were arranged around the circumference of a circle (Experiment 3). These findings suggest that the contribution of visual marking depends on the configuration of search items; with complex displays, prioritizing selection for new objects is more effective if coupled with de-prioritizing de-selection for old objects. PMID- 27001342 TI - Absorption of plant lignans from cereals in an experimental pig model. AB - Plant lignans are diphenolic compounds ingested with whole grains and seeds and converted to enterolignans by the colonic microbiota. In the present study, we investigated absorption and metabolism of plant lignans and enterolignans in vivo after consumption of cereal-based diets. Six pigs fitted with catheters in the mesenteric artery and portal vein and with a flow probe attached to the portal vein along with twenty pigs for quantitative collection of urine were used for this study. The animals were fed bread based on wheat flour low in plant lignans and three lignan-rich breads based on whole-wheat grain, wheat aleurone flour or rye aleurone flour. Plant lignans and enterolignans in plasma were monitored daily at fast after 0-3 d of lignan-rich intake, and on the 4th day of lignan rich intake a 10-h profile was completed. Urine samples were collected after 11 d of lignan-rich diet consumption. The concentrations of plant lignans were low at fast, and was 1.2-2.6 nmol/l after switching from the low-lignan diet to the lignan-rich diets. However, on the profile day, the concentration and quantitative absorption of plant lignans increased significantly from 33 nmol/h at fast to 310 nmol/h 0-2.5 h after ingestion with a gradual increase in the following periods. Quantitatively, the absorption of plant lignans across diets amounted to 7 % of ingested plant lignans, whereas the urinary excretion of plant lignans was 3 % across diets. In conclusion, there is a substantial postprandial uptake of plant lignans from cereals, suggesting that plant lignans are absorbed from the small intestine. PMID- 27001343 TI - Hepatocyte nuclear factor 1 beta induces transformation and epithelial-to mesenchymal transition. AB - Gene amplification can be a cause of cancer, and driver oncogenes have been often identified in amplified regions. However, comprehensive analysis of other genes coamplified with an oncogene is rarely performed. We focused on the 17q12-21 amplicon, which contains ERBB2. We established a screening system for oncogenic activity with the NMuMG epithelial cell line. We identified a homeobox gene, HNF1B, as a novel cooperative transforming gene. HNF1B induced cancerous phenotypes, which were enhanced by the coexpression of ERBB2, and induced epithelial-to-mesenchymal transition and invasive phenotypes. These results suggest that HNF1B is a novel oncogene that can work cooperatively with ERBB2. PMID- 27001344 TI - Prediction of disease-free survival using relative change in FDG-uptake early during neoadjuvant chemoradiotherapy for potentially curable esophageal cancer: A prospective cohort study. AB - 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) has been investigated as a tool for monitoring response to neoadjuvant chemo- and chemoradiotherapy (CT and CRT, respectively) and as a predictor for survival in patients with esophageal cancer. In contrast to patients who undergo neoadjuvant CT, it is not known whether patients who are clinically identified as responders after neoadjuvant CRT show better disease-free survival (DFS) than patients identified as nonresponders. The aim of the study was to determine the predictive value of FDG-uptake measured prior to and early during neoadjuvant CRT. Patients treated with neoadjuvant CRT between 2004 and 2009 within a randomized trial were included. FDG-uptake was measured at baseline and after 14 days of CRT. According to the PERCIST-criteria, patients were allocated to have metabolic response, stable disease, or progression. Patients were followed until recurrence of disease or death. The predictive value of FDG-PET was determined with univariable and multivariable analysis in patients who underwent potentially curative surgery. One-hundred and six patients were included in the analysis. Minimal follow-up for surviving patients was 60 months. No significant differences in DFS were found between patients with metabolic response, stable disease, or progression, with 5-year DFS rates of 66%, 53%, and 67%, respectively (P = 0.39). Relative change in FDG uptake after 14 days of CRT is not associated with DFS in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery. These measurements should not be used for prognostication in this specific group of patients. PMID- 27001345 TI - Selective zircon accumulation in a new benthic foraminifer, Psammophaga zirconia, sp. nov. AB - Benthic foraminifera are single-celled eukaryotes that make a protective organic, agglutinated or calcareous test. Some agglutinated, single-chambered taxa, including Psammophaga Arnold, 1982, retain mineral particles in their cytoplasm, but the selective mechanism of accumulation is not clear. Here, we report the ability of a foraminiferal species to select and accumulate zircons and other heavy minerals in their cytoplasm. In particular, the use of Scanning Electron Microscope coupled with an Energy Dispersive X-ray microanalysis system (SEM-EDS) enabled a representative overview of the mineral diversity and showed that the analysed Psammophaga zirconia sp. nov. individuals contained dominantly crystals of zircon (51%), titanium oxides (27%), and ilmenite (11%) along with minor magnetite and other minerals. The studied specimens occur in the shallow central Adriatic Sea where the sediment has a content of zircon below 1% and of other heavy minerals below 4%. For that reason we hypothesize that: (i) P. zirconia may be able to chemically select minerals, specifically zircon and rutile; (ii) the chemical mechanism allowing the selection is based on electrostatic interaction, and it could work also for agglutinated foraminifera (whether for ingestion, like Xenophyophores, or incorporation in the test as in many other described taxa). In particular, this aptitude for high preferential uptake and differential ingestion or retention of zircon is reported here for the first time, together with the selection of other heavy minerals already described in members of the genus Psammophaga. They are generally counted among early foraminifera, constructing a morphologically simple test with a single chamber. Our molecular phylogenetic study confirms that P. zirconia is a new species, genetically distinctive from other Psammophaga, and occurs in the Adriatic as well as in the Black Sea. PMID- 27001346 TI - Tuning of dye optical properties by environmental effects: a QM/MM and experimental study. AB - The present work is aimed at a deeper investigation of two recently synthesized heteroaromatic fluorophores by means of a computational multilayer approach, integrating quantum mechanics (QM) and molecular mechanics (MM). In particular, dispersion of the title dyes in a polymer matrix is studied in connection with potential applications as photoactive species in luminescent solar concentrators (LSCs). Molecular dynamics simulations, based on accurate QM-derived force fields, reveal increased stiffness of these organic dyes when going from CHCl3 solution to the polymer matrix. QM/MM computations of UV spectra for snapshots extracted from MD simulations show that this different flexibility permits explaining the different spectral shapes obtained experimentally for the two different environments. Moreover, the general spectroscopic trends are reproduced well by static computations employing a polarizable continuum description of environmental effects. PMID- 27001347 TI - Rules of Macrocycle Topology: A [13]-Macrodilactone Case Study. AB - Shape is an inherent trait of a molecule that dictates how it interacts with other molecules, either in binding events or intermolecular reactions. Large-ring macrocyclic compounds in particular leverage their shape when they are selectively bound by biomolecules and also when they exhibit macrocyclic diastereoselectivity. Nonetheless, rules that link structural parameters to the conformation of a macrocycle are still rudimentary. Here we use a structural investigation of a family of [13]-macrodilactones as a case study to develop rules that can be applied generally to macrocycles of different sizes and with a variety of functionality. A characteristic "ribbon" shape is adopted by the [13] macrodilactones in the absence of stereogenic centres, which exhibits planar chirality. When one stereogenic centre at key positions on the backbone is incorporated into the structure, the planar chirality is dictated by the configuration of the centre. In cases where two stereogenic centres are present, their relationships can either reinforce the characteristic ribbon shape or induce alternative shapes to be adopted. The rules established in the case study are then applied to the analysis of a structure of the natural product migrastatin. They lay the groundwork for the development of models to understand macrocycle-biomolecule interactions and for the preparation of macrocycles with designed properties and activities. PMID- 27001348 TI - Nevus Spilus Associated with Agminated Blue Nevus: A Rare Combination. PMID- 27001349 TI - Sarcoidal Necrobiosis Lipoidica in a Nondiabetic Patient: Usefulness of Skin Ultrasound. PMID- 27001350 TI - Order in the absence of an effect: Identifying rate-dependent relationships. AB - The heterogeneity of group data can obscure a significant effect of an intervention due to differential baseline scores. Instead of discarding the seemingly heterogeneous response set, an orderly lawful relationship could be present. Rate dependence describes a pattern between a baseline and the change in that baseline following some intervention. To highlight the importance of analyzing data from a rate-dependent perspective, we (1) briefly review research illustrating that rate-dependent effects can be observed in response to both drug and non-drug interventions in varied schedules of reinforcement in clinical and preclinical populations; (2) observe that the process of rate-dependence likely requires multiple parts of a system operating simultaneously to evoke differential responding as a function of baseline; and (3) describe several statistical methods for consideration and posit that Oldham's correlation is the most appropriate for rate-dependent analyses. Finally, we propose future applications for these analyses in which the level of baseline behavior exhibited prior to an intervention may determine the magnitude and direction of behavior change and can lead to the identification of subpopulations that would be benefitted. In sum, rate dependence is an invaluable perspective to examine data following any intervention in order to identify previously overlooked results. PMID- 27001351 TI - Immunogenicity of an adeno-vector vaccine expressing the F protein of a respiratory syncytial virus manufactured from serum-free suspension culture. AB - We have developed an efficient cell culture process to scale up the production of a recombinant adenovirus that expresses the membrane-trunked fusion protein of respiratory syncytial virus (RSV; Ad-F0DeltaTM). Adherent cells of human embryonic kidney (HEK) 293-derived cell, 293A, which supports the production of E1/E3-deleted Ad-F0DeltaTM when cultured in the presence of fetal bovine serum (FBS), were adapted to suspension growth under serum-free medium. In doing so, we studied the immunogenicity of Ad-F0DeltaTMsus, which propagated in a bioreactor that was cultured with serum-free suspension of 293A, in comparison with Ad F0DeltaTMadh, which was produced from parental 293A cells that were adherently cultured in medium containing FBS. The size and morphology of Ad-F0DeltaTMsus and Ad-F0DeltaTMadh virions were identical upon inspection with electron microscopy. The results showed that anti-F IgG and RSV-neutralizing titer were raised in the serum of both mice that were intranasally immunized twice with Ad-F0DeltaTMsus or Ad-F0DeltaTMadh at two-week injection intervals. Furthermore, the immune responses persisted for six months after vaccination. Activation of F protein specific CD8(+) T cell's epitope associated IFN-gamma and IL-4 was induced in both Ad-F0DeltaTMsus- and Ad-F0DeltaTMadh, but not in Ad-LacZsus, -immunized mouse splenocytes. No vaccine-enhanced lung inflammation, airway mucus occlusion or eosinophils infiltration were observed in Ad-immunized mice followed by RSV challenge; however, these symptoms were observed following immunization with formalin-inactivated RSV vaccine. These results indicate that the safety and potency of Ad-F0DeltaTM produced from either adherent cells or suspension and serum-free cells are the same. PMID- 27001352 TI - Mechanics of the eukaryotic flagellar axoneme: Evidence for structural distortion during bending. AB - The sliding doublet mechanism is the established explanation that allows us to understand the process of ciliary and flagellar bending. In this study, we apply the principles of the sliding doublet mechanism to analyze the mechanics of the counterbend phenomenon in sea urchin sperm flagella. When a passive, vanadate treated, flagellum is forced into a bend with a glass microprobe, the portion of the flagellum distal to the probe exhibits a bend of opposite curvature (counterbend) to the imposed bend. This phenomenon was shown to be caused by the induction of inter-doublet shear and is dependent on the presence of an inter doublet shear resistance. Here we report that in sea urchin flagella there is systematically less shear induced in the distal flagellum than is predicted by the sliding doublet mechanism, if we follow the assumption that the diameter of the flagellum is uniform. To account for the reduced shear that is observed, the likeliest and most direct interpretation is that the portion of the axoneme that is forced to bend undergoes substantial compression of the axoneme in the bending plane. A compression of 30-50 nm would be sufficient to account for the shear reduction from a bend of 2 radians. A compression of this magnitude would require considerable flexibility in the axoneme structure. This would necessitate that the radial spokes and/or the central pair apparatus are easily compressed by transverse stress. (c) 2016 Wiley Periodicals, Inc. PMID- 27001353 TI - Enhanced all-optical modulation in a graphene-coated fibre with low insertion loss. AB - Graphene is a highly versatile two-dimensional material platform that offers exceptional optical and electrical properties. Of these, its dynamic conductivity and low effective carrier mass are of particular interest for optoelectronic applications as they underpin the material's broadband nonlinear optical absorption and ultra-fast carrier mobility, respectively. In this paper, we utilize these phenomena to demonstrate a high-speed, in-fibre optical modulator developed on a side-polished optical fibre platform. An especially low insertion loss (<1 dB) was achieved by polishing the fibre to a near atomically smooth surface (<1 nm RMS), which minimized scattering and ensured excellent contact between the graphene film and the fibre. In order to enhance the light-matter interaction, the graphene film is coated with a high index polyvinyl butyral layer, which has the added advantage of acting as a barrier to the surrounding environment. Using this innovative approach, we have fabricated a robust and stable all-fibre device with an extinction ratio as high as 9 dB and operation bandwidth of 0.5 THz. These results represent a key step towards the integration of low-dimensional materials within standard telecoms networks. PMID- 27001354 TI - A tailored treatment strategy: a modern approach for stroke prevention in patients with atrial fibrillation. AB - The main priority in atrial fibrillation (AF) management is stroke prevention, following which decisions about rate or rhythm control are focused on the patient, being primarily for management of symptoms. Given that AF is commonly associated with various comorbidities, risk factors such as hypertension, heart failure, diabetes mellitus and sleep apnoea should be actively looked for and managed in a holistic approach to AF management. The objective of this review is to provide an overview of modern AF stroke prevention with a focus on tailored treatment strategies. Biomarkers and genetic factors have been proposed to help identify 'high-risk' patients to be targeted for oral anticoagulation, but ultimately their use must be balanced against that of more simple and practical considerations for everyday use. Current guidelines have directed focus on initial identification of 'truly low-risk' patients with AF, that is those patients with a CHA2 DS2 -VASc [congestive heart failure, hypertension, age >=75 years (two points), diabetes mellitus, stroke (two points), vascular disease, age 65-74 years, sex category] score of 0 (male) or 1 (female), who do not need any antithrombotic therapy. Subsequently, patients with >=1 stroke risk factors can be offered effective stroke prevention, that is oral anticoagulation. The SAMe TT2 R2 [sex female, age <60 years, medical history (>2 comorbidities), treatment (interacting drugs), tobacco use (two points), race non-Caucasian (two points)] score can help physicians make informed decisions on those patients likely to do well on warfarin (SAMe-TT2 R2 score 0-2) or those who are likely to have a poor time in therapeutic range (SAMe-TT2 R2 score >2). A clinically focused tailored approach to assessment and stroke prevention in AF with the use of the CHA2 DS2 VASc, HAS-BLED [hypertension, abnormal renal/liver function (one or two points), stroke, bleeding history or predisposition, labile international normalized ratio, elderly (>65 years) drugs/alcohol concomitantly (one or two points)] and SAMeTT2 R2 scores to evaluate stroke risk, bleeding risk and likelihood of successful warfarin therapy, respectively, is discussed. PMID- 27001356 TI - Comprehensive US government program for dried plasma development. AB - Transfusion of plasma early after severe injury has been associated with improved survival. There are significant logistic factors that limit the ability to deliver plasma where needed in austere environments, such as the battlefield or during a significant civilian emergency. While some countries have access to more logistically supportable dried plasma, there is no such product approved for use in the United States. There is a clear need for a Food and Drug Administration (FDA)-approved dried plasma for military and emergency-preparedness uses, as well as for civilian use in remote or austere settings. The Department of Defense (DoD) and Biomedical Advanced Research and Development Authority are sponsoring development of three dried plasma products, incorporating different technologic approaches and business models. At the same time, the DoD is sponsoring prospective, randomized clinical studies on the prehospital use of plasma. These efforts are part of a coordinated program to provide a dried plasma for military and civilian applications and to produce additional information on plasma use so that, by the time we have an FDA-approved dried plasma, we will better understand how to use it. PMID- 27001357 TI - Efficacy and safety of pathogen-reduced platelet concentrates in children with cancer: a retrospective cohort study. AB - BACKGROUND: The safety of blood component transfusions is still of concern and the use of pathogen reduction (PR) methods is increasing. Limited data are available describing safety and efficacy of PR platelet (PLT) transfusions in children. We report the results of a retrospective evaluation of prophylactic transfusions of PR PLT units treated with riboflavin and ultraviolet light in pediatric patients with malignant disorders. STUDY DESIGN AND METHODS: A total of 137 patients (PR, 51; control, 86) and 432 transfusions (PR, 141; control, 291) with mean age of 11 years were evaluated. The primary clinical efficacy endpoint was the proportion of patients with bleeding on any day of PLT support. Secondary endpoints included 1- and 24-hour PLT increments, corrected count increments (CCIs), and the number of days between PLT transfusions. Safety endpoints included number of posttransfusion adverse reactions. RESULTS: The incidence of bleeding events, severity, and localization of bleeding sites did not differ between the study groups. Posttransfusion PLT counts and 1- and 4-hour CCIs (12.25 +/- 4.26 and 25.67 +/- 7.11; p < 0.05; PR vs. control, respectively) and 18- to 24-hour CCIs (9.41 +/- 6.42 and 12.47 +/- 6.25; p < 0.05) after transfusions were significantly lower in the PR group. Transfusion-related adverse event rates did not differ between groups (8.3% vs. 9.8%, p = 0.73). CONCLUSION: In spite of lower numerical increase in PLT count, the hemostatic efficacy and safety of PR PLT transfusions was comparable with the control group. Adverse event rates did not differ between groups, but the sample size was relatively small. PMID- 27001358 TI - The role of hemovigilance and postmarketing studies when introducing innovation into transfusion medicine practice: the amotosalen-ultraviolet A pathogen reduction treatment model. AB - BACKGROUND: Innovations in transfusion medicine require randomized controlled clinical trials (RCTs) to demonstrate safety and efficacy before approval; however, these studies are costly and limited in scope and may be underpowered to detect rare adverse events (AEs). Regulatory agencies, such as the Food and Drug Administration, require postmarketing surveillance, hemovigilance (HV), and controlled Phase IV studies to monitor performance and confirm safety. STUDY DESIGN AND METHODS: The INTERCEPT Blood System (IBS) is an illustrative model for implementation of a transformative technology for which sponsored active HV, regulatory authority HV, and Phase IV studies were used to extend preapproval efficacy and safety information. RESULTS: After CE mark registration in Europe, 13,644 patients received 76,346 IBS components prepared largely without gamma irradiation or bacterial screening in sponsored active HV studies documenting no increased incidence of AEs compared to historical controls and no increased component utilization. National HV systems in France and Switzerland specifically demonstrated no transfusion-associated graft-versus-host disease or increased incidence of transfusion-associated acute lung injury, after transfusion of 317,669 IBS platelet (PLT) components, and significant reduction of transfusion transmitted bacterial infection as well as acute transfusion reactions. Cumulatively, these studies provide new information about safety and efficacy of IBS PLT and plasma components not obtainable from RCTs. CONCLUSION: Although inherently different from RCTs, properly designed postmarketing studies are informative regarding the safety and efficacy of innovative transfusion technologies in large patient populations under conditions of routine use. PMID- 27001359 TI - What is innovation? PMID- 27001360 TI - Hemovigilance survey of pathogen-reduced blood components in the Warsaw Region in the 2009 to 2013 period. AB - BACKGROUND: In 2009 the Mirasol Pathogen Reduction Technology (PRT) was introduced to the routine blood component production of the Regional Blood Transfusion Center in Warsaw (RBTCW). The goal of this study was to investigate the safety of Mirasol-treated blood components. STUDY DESIGN AND METHODS: The accumulated passive hemovigilance data of Mirasol-treated blood components collected at the RBTCW are presented and compared to historical and contemporary data. Furthermore, active hemovigilance data collected from patients with different hematologic disorders transfused with Mirasol-treated or untreated blood components at the Institute of Hematology and Transfusion Medicine (IHTM) are presented and discussed. RESULTS: The adverse reaction (AR) reporting rate by hospitals to the RBTCW after the implementation of the Mirasol technology was 0.39% for Mirasol-treated platelet concentrates (M-PCs) and 0.05% for Mirasol treated fresh-frozen plasma. When comparing contemporary rates of ARs recorded by RBTCW in the time period 2011 to 2012, no statistical difference was observed between Mirasol-treated and untreated blood components. No serious AR was attributed to Mirasol-treated components. At the IHTM a lower rate of ARs after transfusion of M-PCs was observed than with untreated PCs. Despite the fact that very large amounts of Mirasol-treated plasma have been transfused to patients with congenital or acquired thrombotic thrombocytopenic purpura, no significant increase in AR rates was observed. CONCLUSION: Treatment of blood components with the Mirasol PRT System has proven to be safe for patients and is not associated with increased rates and grades of adverse events in patients of hospitals in the Warsaw Region. PMID- 27001361 TI - Transfusion-transmitted leishmaniasis: a practical review. AB - In the Balearic Islands, as in other areas in southern Europe, there are a significant proportion of asymptomatic Leishmania infantum-infected blood donors. Theoretically, these donors may represent an important challenge for blood transfusion safety. However, despite an active search of multiply transfused patients, there have been, so far, no cases of transfusion-transmitted leishmaniasis (TTL) in our region. On the other hand, there is scarce evidence of the TTL in the literature. A review of asymptomatic Leishmania-infected blood donors' studies in endemic areas and TTL reports published in the English literature were performed, to ascertain the factors that determine the real risk of transfusion transmission of Leishmania. PMID- 27001362 TI - The effects of 22 degrees C and 4 degrees C storage of platelets on vascular endothelial integrity and function. AB - BACKGROUND: Although a majority of the studies conducted to date on platelet (PLT) storage have been focused on PLT hemostatic function, the effects of 4 degrees C PLTs on regulation of endothelial barrier permeability are still not known. In this study, we compared the effects of room temperature (22 degrees C) stored and (4 degrees C) stored PLTs on the regulation of vascular endothelial cell (EC) permeability in vitro and in vivo. STUDY DESIGN AND METHODS: Day 1, Day 5, and Day 7 leukoreduced apheresis PLTs stored at 4 or 22 degrees C were studied in vitro and in vivo. In vitro, PLT effects on EC permeability and barrier function, adhesion, and impedance aggregometry were investigated. In vivo, using a mouse model of vascular leak, attenuation of vascular leak and circulating PLT numbers were measured. RESULTS: Treatment of EC monolayers with Day 5 or Day 7 PLTs, stored at both 22 degrees C and 4 degrees C, resulted in similar decreases in EC permeability on average. However, analysis of individual samples revealed significant variation that was donor dependent. Additional in vitro measurements revealed a decrease in inflammatory mediators, nonspecific PLT-endothelial aggregation and attenuated loss of aggregation over time to TRAP, ASPI, ADP, and collagen with 4 degrees C storage. In mice, while 22 degrees C and 4 degrees C PLTs both demonstrated significant protection against vascular endothelial growth factor A (VEGF-A)-induced vascular leak 22 degrees C PLTs exhibited increased protection compared to 4 degrees C PLTs. Systemic circulating levels of 4 degrees C PLTs were decreased compared to 22 degrees C PLTs. CONCLUSIONS: In vitro, 4 degrees C-stored PLTs exhibit a greater capacity to inhibit EC permeability than 22 degrees C-stored PLTs. In vivo, 22 degrees C PLTs provide superior control of vascular leak induced by VEGF-A. This discrepancy may be due to increased clearance of 4 degrees C PLTs from the systemic circulation. PMID- 27001363 TI - Treatment of blood with a pathogen reduction technology using ultraviolet light and riboflavin inactivates Ebola virus in vitro. AB - BACKGROUND: Transfusion of plasma from recovered patients after Ebolavirus (EBOV) infection, typically called "convalescent plasma," is an effective treatment for active disease available in endemic areas, but carries the risk of introducing other pathogens, including other strains of EBOV. A pathogen reduction technology using ultraviolet light and riboflavin (UV+RB) is effective against multiple enveloped, negative-sense, single-stranded RNA viruses that are similar in structure to EBOV. We hypothesized that UV+RB is effective against EBOV in blood products without activating complement or reducing protective immunoglobulin titers that are important for the treatment of Ebola virus disease (EVD). STUDY DESIGN AND METHODS: Four in vitro experiments were conducted to evaluate effects of UV+RB on green fluorescent protein EBOV (EBOV-GFP), wild-type EBOV in serum, and whole blood, respectively, and on immunoglobulins and complement in plasma. Initial titers for Experiments 1 to 3 were 4.21 log GFP units/mL, 4.96 log infectious units/mL, and 4.23 log plaque-forming units/mL. Conditions tested in the first three experiments included the following: 1-EBOV-GFP plus UV+RB; 2-EBOV GFP plus RB only; 3-EBOV-GFP plus UV only; 4-EBOV-GFP without RB or UV; 5-virus free control plus UV only; and 6-virus-free control without RB or UV. RESULTS: UV+RB reduced EBOV titers to nondetectable levels in both nonhuman primate serum (>=2.8- to 3.2-log reduction) and human whole blood (>=3.0-log reduction) without decreasing protective antibody titers in human plasma. CONCLUSION: Our in vitro results demonstrate that the UV+RB treatment efficiently reduces EBOV titers to below limits of detection in both serum and whole blood. In vivo testing to determine whether UV+RB can improve convalescent blood product safety is indicated. PMID- 27001365 TI - Bioenergetic profiling of platelet mitochondria during storage: 4 degrees C storage extends platelet mitochondrial function and viability. AB - BACKGROUND: Platelets (PLTs) are stored at room temperature (RT) to preserve in vivo circulation time, but PLT quality is degraded. The PLT storage lesion is mitigated by refrigeration, but questions remain regarding effects of cold storage (4 degrees C) on mitochondrial function. Mitochondrial reactive oxygen species (ROS) generation may adversely affect PLT function and viability during storage, and refrigeration may mitigate these effects. STUDY DESIGN AND METHODS: PLTs were stored under two temperature conditions (RT, 20-24 degrees C; or 4 degrees C, 1-6 degrees C) and four storage durations (baseline [BL] and Days 3, 5, and 7). Mitochondrial respiration and maximal oxygen utilization were assessed with high-resolution respirometry. Mitochondrial ROS generation was assessed using a superoxide stain. Rotational thromboelastometry (ROTEM) was performed at BL and on Day 5 to assess PLT function. Collagen-induced PLT aggregation was measured by impedance aggregometry. RESULTS: Mitochondrial ROS in 4 degrees C stored samples were lower compared to RT and retained a greater capacity to generate ROS after activation. Mitochondrial respiration and maximal mitochondrial utilization was conserved in PLTs stored at 4 degrees C. ROTEM data demonstrated that net maximum clot firmness was higher in 4 degrees C samples compared to RT and prevented fibrinolysis. The aggregation response to collagen was preserved in the 4 degrees C samples versus RT-stored PLTs. Aggregation impairment correlated well with attenuated mitochondrial respiration and elevated production of intracellular mitochondrial ROS in the RT PLTs. CONCLUSION: Mitochondrial damage and ROS production may contribute to loss of PLT viability during storage, whereas cold storage is known to preserve PLT function. Here we demonstrate that 4 degrees C storage results in less oxidant stress and preserves mitochondrial function and potential compared to RT. PMID- 27001364 TI - Platelets regulate vascular endothelial stability: assessing the storage lesion and donor variability of apheresis platelets. AB - BACKGROUND: In current blood banking practices, platelets (PLTs) are stored in plasma at 22 degrees C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known. STUDY DESIGN AND METHODS: In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry. RESULTS: Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A-induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A-challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs CONCLUSIONS: In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22 degrees C, thereby suggesting that Day 5 PLTs are diminished in their ability to attenuate vascular endothelial permeability. PMID- 27001366 TI - US Army blood program: 2025 and beyond. AB - In preparing to support the Army in 2025 and beyond, the Army Blood Program remains actively engaged with the research and advanced development of blood products and medical technology to improve blood safety and efficacy in conjunction with the US Army Medical Research and Materiel Command. National and International Blood Bank authorities have noted that the US Army research and development efforts in providing new blood products and improving blood safety operate on the cutting edge of technology and are transformational for the global blood industry. Over the past 14 years, the Army has transformed how blood support is provided and improved the survival rate of casualties. Almost every product or process developed by or for the military has found an application in treating civilian patients. Conflicts have many unwanted consequences; however, in times of conflict, one positive aspect is the identification of novel solutions to improve the safety and efficacy of the blood supply. PMID- 27001367 TI - Patient blood management: the global view. PMID- 27001368 TI - Macrophages Aggravate Hypoxia-Induced Cardiac Microvascular Endothelial Cell Injury via Peroxynitrite: Protection by Tongxinluo. AB - Activated macrophages contribute to endothelial dysfunction; however, it is unclear how peroxynitrite contributes to macrophage-mediated human cardiac microvascular endothelial cell (HCMEC) injury in hypoxia. In macrophage-HCMEC co cultures subjected to hypoxia, there was an increase in hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, inducible nitric oxide synthase (iNOS), endothelin converting enzyme (ECE)-1 and cyclooxygenase-2 (COX-2), and concomitant decrease in prostacyclin synthase (PGIS). This was mimicked by a peroxynitrite donor and attenuated by its decomposition catalyst. Tongxinluo (TXL) could decrease HIF 2alpha, iNOS, ECE-1 and COX-2 and increase PGIS in a dose-dependent manner, with increase of vascular endothelial growth factor. The protein alterations verified the remarkably affected mRNAs, indicating that the effects of TXL were similar to but better than that of peroxynitrite decomposition catalyst. Furthermore, TXL inhibited macrophage-mediated nitrotyrosine accumulation and attenuated HCMEC injury. The results suggest that peroxynitrite contributes to macrophage-mediated HCMEC injury in hypoxia, and TXL attenuates HCMEC injury mainly by inhibiting peroxynitrite. PMID- 27001369 TI - Dose-dependent autophagic effect of titanium dioxide nanoparticles in human HaCaT cells at non-cytotoxic levels. AB - BACKGROUND: Interactions between nanoparticles and cells are now the focus of a fast-growing area of research. Though many nanoparticles interact with cells without any acute toxic responses, metal oxide nanoparticles including those composed of titanium dioxide (TiO2-NPs) may disrupt the intracellular process of macroautophagy. Autophagy plays a key role in human health and disease, particularly in cancer and neurodegenerative diseases. We herein investigated the in vitro biological effects of TiO2-NPs (18 nm) on autophagy in human keratinocytes (HaCaT) cells at non-cytotoxic levels. RESULTS: TiO2-NPs were characterized by transmission electron microscopy (TEM) and dynamic light scattering techniques. Cellular uptake, as evaluated by TEM and NanoSIMS revealed that NPs internalization led to the formation of autophagosomes. TiO2-NPs treatment did not reduce cell viability of HaCaT cells nor increased oxidative stress. Cellular autophagy was additionally evaluated by confocal microscopy using eGFP-LC3 keratinocytes, western blotting of autophagy marker LC3I/II, immunodetection of p62 and NBR1 proteins, and gene expression of LC3II, p62, NBR1, beclin1 and ATG5 by RT-qPCR. We also confirmed the formation and accumulation of autophagosomes in NPs treated cells with LC3-II upregulation. Based on the lack of degradation of p62 and NBR1 proteins, autophagosomes accumulation at a high dose (25.0 MUg/ml) is due to blockage while a low dose (0.16 MUg/ml) promoted autophagy. Cellular viability was not affected in either case. CONCLUSIONS: The uptake of TiO2-NPs led to a dose-dependent increase in autophagic effect under non-cytotoxic conditions. Our results suggest dose dependent autophagic effect over time as a cellular response to TiO2-NPs. Most importantly, these findings suggest that simple toxicity data are not enough to understand the full impact of TiO2-NPs and their effects on cellular pathways or function. PMID- 27001370 TI - An in-situ gas chromatography investigation into the suppression of oxygen gas evolution by coated amorphous cobalt-phosphate nanoparticles on oxide electrode. AB - The real time detection of quantitative oxygen release from the cathode is performed by in-situ Gas Chromatography as a tool to not only determine the amount of oxygen release from a lithium-ion cell but also to address the safety concerns. This in-situ gas chromatography technique monitoring the gas evolution during electrochemical reaction presents opportunities to clearly understand the effect of surface modification and predict on the cathode stability. The oxide cathode, 0.5Li2MnO3?0.5LiNi0.4Co0.2Mn0.4O2, surface modified by amorphous cobalt phosphate nanoparticles (a-CoPO4) is prepared by a simple co-precipitation reaction followed by a mild heat treatment. The presence of a 40 nm thick a-CoPO4 coating layer wrapping the oxide powders is confirmed by electron microscopy. The electrochemical measurements reveal that the a-CoPO4 coated overlithiated layered oxide cathode shows better performances than the pristine counterpart. The enhanced performance of the surface modified oxide is attributed to the uniformly coated Co-P-O layer facilitating the suppression of O2 evolution and offering potential lithium host sites. Further, the formation of a stable SEI layer protecting electrolyte decomposition also contributes to enhanced stabilities with lesser voltage decay. The in-situ gas chromatography technique to study electrode safety offers opportunities to investigate the safety issues of a variety of nanostructured electrodes. PMID- 27001371 TI - Sclerostin levels in uremic patients: a link between bone and vascular disease. AB - Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 +/- 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 +/- 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy. PMID- 27001372 TI - Do the ball-ended probe cause less damage than sharp explorers?-An ultrastructural analysis. AB - BACKGROUND: No evidence about damage caused by ball-ended probes on tooth is available. No study compared probing defects caused by ball-ended probes with sharp explorers during tactile examinations of primary teeth. This exploratory study aimed to compare ultrastructural defects caused by ball-ended probes with sharp explorers during tactile examinations of primary teeth. METHODS: Forty-nine primary extracted teeth were tactile examined as performed for caries activity assessment. Surfaces were randomly divided into groups based on probe type (ball ended probe or sharp explorer). Two examiners probed different surfaces using the sharp explorer and the ball-ended probe. The order for examination was randomly determined. Images were captured using environmental scanning electron microscopy (ESEM) before and after probing. Two external examiners evaluated independently the ESEM images and scored them as: 0) no damage, 1) slight marks, 2) distinct marks, 3) marks with discontinuity, 4) enamel break-offs. Multilevel Poisson regression models were used to analyze associations between probing ultrastructural damage and surface type, baseline condition and probe type. Prevalence ratios (PR) were calculated with 95 % confidence interval (CI). RESULTS: The most common defects observed on the dental surfaces were probing marks without discontinuity (scores 1 and 2). Ball-ended probes caused significantly less severe damage than sharp explorers (PR: 0.28; CI: 0.11-0.76, p = 0.01). CONCLUSION: Ball-ended probes cause less damage than sharp explorers when probing gently dental surfaces of primary teeth. PMID- 27001373 TI - Adjusting an Available Online Peer Support Platform in a Program to Supplement the Treatment of Perinatal Depression and Anxiety. AB - BACKGROUND: Perinatal depression and anxiety are common and debilitating conditions. Novel, cost effective services could improve the uptake and the impact of mental health resources among women who suffer from these conditions. E mental health products are one example of such services. Many publically available e-mental health products exist, but these products lack validation and are not designed to be integrated into existing health care settings. OBJECTIVE: The objective of the study was to present a program to use 7 Cups of Tea (7Cups), an available technological platform that provides online peer (ie, listener) based emotional support, to supplement treatment for women experiencing perinatal depression or anxiety and to summarize patient's feedback on the resultant program. METHODS: This study consisted of two stages. First, five clinicians specializing in the treatment of perinatal mood disorders received an overview of 7Cups. They provided feedback on the 7Cups platform and ways it could complement the existing treatment efforts to inform further adjustments. In the second stage, nine women with perinatal depression or anxiety used the platform for a single session and provided feedback. RESULTS: In response to clinicians' feedback, guidelines for referring patients to use 7Cups as a supplement for treatment were created, and a training program for listeners was developed. Patients found the platform usable and useful and their attitudes toward the trained listeners were positive. Overall, patients noted a need for support outside the scheduled therapy time and believed that freely available online emotional support could help meet this need. Most patients were interested in receiving support from first time mothers and those who suffered in the past from perinatal mood disorders. CONCLUSIONS: The study results highlight the use of 7Cups as a tool to introduce accessible and available support into existing treatment for women who suffer from perinatal mood disorders. Further research should focus on the benefits accrued from such a service. However, this article highlights how a publicly available eHealth product can be leveraged to create new services in a health care setting. PMID- 27001374 TI - Functional adaptation of the masticatory system to implant-supported mandibular overdentures. AB - OBJECTIVES: The purpose of this study was to investigate the adaptation behavior of the stomatognathic system after immediate loading (24 to 72 h after surgery) of two implants supporting mandibular overdentures, assessed on insertion and three months later. The study hypothesis was that insertion of the overdentures would significantly change masticatory performance and muscle activity at both times. MATERIAL AND METHODS: Thirty subjects (nine female, mean age 69.64 +/- 11.81 years; 21 male, mean age 68.67 +/- 7.41 years) who participated in a randomized clinical trial were included in the study. Each patient was examined three times: (i) at baseline, after already having worn new dentures for three months (T1); (ii) immediately after insertion of the overdentures on the implants (T2); and (iii) after an adaptation period of three months (T3). Examination comprised assessment of masticatory performance with artificial test food (Optocal), and simultaneous bilateral surface EMG recording of the masseter and anterior temporalis muscles. Particle-size distribution (representative value X50 ), maximum muscle contraction (MVC), and total muscle work (TMW; area under the curve) were compared by use of repeated-measures analysis of variance (ANOVA). RESULTS: At T3, all measured variables (i.e., masticatory performance and muscle activity) were significantly different from those at T1. At T2, no significant changes were observed. The study hypothesis had to be rejected for T2 but accepted for T3. CONCLUSION: Functional rehabilitation (in terms of masticatory performance and masticatory muscle activity) does not occur immediately after immediate loading of two implants with mandibular overdentures, but requires a significant time for functional improvement. PMID- 27001375 TI - Chemoselective Sequential Click Ligations Directed by Enhanced Reactivity of an Aromatic Ynamine. AB - Aromatic ynamines or N-alkynylheteroarenes are highly reactive alkyne components in Cu-catalyzed Huisgen [3 + 2] cycloaddition ("click") reactions. This enhanced reactivity enables the chemoselective formation of 1,4-triazoles using the representative aromatic ynamine N-ethynylbenzimidazole in the presence of a competing aliphatic alkyne substrate. The unique chemoselectivity profile of N ethynylbenzimidazole is further demonstrated by the sequential click ligation of a series of highly functionalized azides using a heterobifunctional diyne, dispelling the need for alkyne protecting groups. PMID- 27001376 TI - INTEGRATING HEALTH TECHNOLOGY ASSESSMENT PRINCIPLES IN FORMULARY MANAGEMENT. AB - OBJECTIVES: Effective formulary management in healthcare institutions safeguards rational drug use and optimizes health outcomes. We implemented a formulary management program integrating the principles of health technology assessment (HTA) to improve the safe, appropriate, and cost-effective use of medicine in Singapore. METHODS: A 3-year formulary management program was initiated in 2011 in five public healthcare institutions. This program was managed by a project team comprising HTA researchers. The project team worked with institutional pharmacy and therapeutics (P&T) committees to: (i) develop tools for formulary drug review and decision making; (ii) enhance the HTA knowledge and skills of formulary pharmacists and members of P&T committees; (iii) devise a prioritization framework to overcome resource constraints and time pressure; and (iv) conceptualize and implement a framework to review existing formulary. RESULTS: Tools that facilitate drug request submission, drug review, and decision making were developed for formulary drug inclusion. A systematic framework to review existing formulary was also developed and tested in selected institutions. A competency development plan was rolled out over 2 years to enhance formulary pharmacists' proficiency in systematic literature search and review, meta analysis, and pharmacoeconomic evaluation. The plan comprised training workshops and on-the-job knowledge transfer between the project team and institutional formulary pharmacists through collaborating on selected drug reviews. A resource guide that consolidated the tools and templates was published to encourage the adoption of best practices in formulary management. CONCLUSIONS: Based on the concepts of HTA, we implemented an evidence-based approach to optimize formulary management. PMID- 27001377 TI - Involvement of nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test. AB - Antidepressant-like effects of 5-hydroxytryptamine subtype 3 (5-HT3) antagonists including tropisetron and ondansetron have been previously demonstrated in the literature. It was reported that stimulation of 5-HT3 receptors activate the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, which is involved in regulation of behavioral and emotional functions. In our study, treating animals with tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01 and 0.1ug/kg) significantly decreased the immobility time in forced swimming test (FST) and tail-suspension test (TST). Co-administration of subeffective doses of tropisetron (1mg/kg) and ondansetron (0.001ug/kg) with subeffective dose of l NAME (10mg/kg, nonselective NO synthase (NOS) inhibitor) and 7-nitroindazole (25mg/kg, neural NOS inhibitor) exerted antidepressant-like effect in FST and TST, while aminoguanidine (50mg/kg, inducible NOS inhibitor) did not enhance the antidepressant-like effect of 5-HT3 antagonists. Besides, l-arginine (750mg/kg, NO precursor) and sildenafil (5mg/kg, phosphodiesterase inhibitor) suppressed the anti-immobility effect of 5-HT3 antagonists. None of the treatments altered the locomotor behavior of mice in open-field test. Also, hippocampal (but not cortical) nitrite level was significantly lower in tropisetron and ondansetron treated mice compared with saline-injected mice. Also, co-administration of 7 nitroindazole with tropisetron or ondansetron caused a significant decrease in hippocampal nitrite levels. In conclusion, we suggest that antidepressant-like effect of tropisetron and ondansetron are partially mediated by modulation of NO cGMP pathway. PMID- 27001378 TI - Inhibition of c-Rel DNA binding is critical for the anti-inflammatory effects of novel PIKfyve inhibitor. AB - Aberrant production of proinflammatory cytokines is linked to many autoimmune diseases, and their inhibition by small molecule compounds is considered beneficial. Here, we performed phenotypic screening in IFNgamma/LPS-activated RAW264.7, mouse macrophage cells, and discovered AS2677131 and AS2795440 as novel and potent inhibitors of IL-12p40, a subunit of IL-23. Interestingly, these compounds exhibited unique pharmacological activities in their inhibition of the production of IL-12p40, IL-6 and IL-1beta but not TNFalpha in activated macrophages or dendritic cells, and expression of IgM-induced MHC class II on B cells. To reveal these mechanisms, we synthesized two different activity probes which were structurally related to the AS compounds, and identified probe specific binding proteins, including PIKfyve, a Class III PI kinase. The AS compounds inhibited PIKfyve activity and mimicked the properties of PIKfyve deficient cells, eventually validating PIKfyve as target molecule. Regarding mechanism, AS2677131 regulated DNA binding activity of c-Rel on IL-12p40 and IL 1beta promoter. As expected, a PIKfyve inhibitor prevented the development of arthritis in rats. Taken together, our findings of the novel and potent PIKfyve inhibitors AS2677131 and AS2795440 reveal the critical role of PIKfyve in proinflammatory cytokine production and B cell activation, and may indicate a potential new therapeutic option for treatment of inflammatory diseases. PMID- 27001379 TI - Disclosure of medical errors involving gametes and embryos: an Ethics Committee opinion. AB - Medical providers have an ethical duty to disclose clinically significant errors involving gametes and embryos as soon as they are discovered. Clinics also should have written policies in place for reducing and disclosing errors. This document was reviewed and affirmed in 2015 and replaces the earlier document of the same name (Fertil Steril 2011;96:1312-4). PMID- 27001380 TI - Defining embryo donation: an Ethics Committee opinion. AB - Building families through the adoption of children has been supported by human society throughout history. The ethical appropriateness of patients donating embryos to other patients for family building, or for research, is well established and is affirmed by this Committee. The use of the term ''adoption'' for embryos is inaccurate and should be avoided. This document replaces the ASRM Ethics Committee statement by the same name, last published in 2013 (Fertil Steril 2013;99:1846-7). PMID- 27001381 TI - Future evaluation and treatment of unexplained infertility. PMID- 27001382 TI - Risk factors for ectopic pregnancy in assisted reproductive technology: a 6-year, single-center study. AB - OBJECTIVE: To explore factors affecting the incidence of ectopic pregnancy (EP) in assisted reproductive technology (ART). DESIGN: A retrospective cohort study on the incidence of EPs in IVF/intracytoplasmic sperm injection (ICSI) and IUI cycles from June 2009 to August 2015. Age of patients, tubal factor infertility, type of cycle (fresh or thawed), embryo being transferred (cleavage embryo or blastocyst), and number of embryos transferred were analyzed to explore their relationship with the incidence of EP. SETTING: Teaching hospital. PATIENT(S): A total of 18,432 pregnancies resulting from ART treatment were retrospectively analyzed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ectopic pregnancy rate. RESULT(S): For IVF/ICSI cycles, the incidence of EP was different between cycles transferred with cleavage embryo and blastocyst (3.45% vs. 2.47%). In multivariate logistic regression analysis, tubal infertility was associated with EP (adjusted odds ratio 1.716, 95% confidence interval 1.444-2.039). For IUI cycles, EP was significantly higher in stimulated cycles compared with natural cycles (2.62% vs. 0.99%). The EP rate in cycles with sperm from donor and husband was 1.08% and 3.54%, respectively. However, when patients were stratified according to tubal infertility, the EP rate increased with level of peak estrogen. In thawed embryo transfer cycles, the EP rate was lower in blastocyst transfer cycles and in cycles transferred with fewer embryos. CONCLUSION(S): Irrespective of tubal infertility, for fresh IVF/ICSI cycles the rate of EP is positively associated with ovarian stimulation; for thawed IVF/ICSI cycles, blastocyst transfer or transfer with fewer embryos reduces the EP rate. In IUI cycles, EP is associated with sperm source. PMID- 27001383 TI - Pure animal phobia is more specific than other specific phobias: epidemiological evidence from the Zurich Study, the ZInEP and the PsyCoLaus. AB - Interest in subtypes of mental disorders is growing in parallel with continuing research progress in psychiatry. The aim of this study was to examine pure animal phobia in contrast to other specific phobias and a mixed subtype. Data from three representative Swiss community samples were analysed: PsyCoLaus (n = 3720), the ZInEP Epidemiology Survey (n = 1500) and the Zurich Study (n = 591). Pure animal phobia and mixed animal/other specific phobias consistently displayed a low age at onset of first symptoms (8-12 years) and clear preponderance of females (OR > 3). Meanwhile, other specific phobias started up to 10 years later and displayed almost a balanced sex ratio. Pure animal phobia showed no associations with any included risk factors and comorbid disorders, in contrast to numerous associations found in the mixed subtype and in other specific phobias. Across the whole range of epidemiological parameters examined in three different samples, pure animal phobia seems to represent a different entity compared to other specific phobias. The etiopathogenetic mechanisms and risk factors associated with pure animal phobias appear less clear than ever. PMID- 27001384 TI - Optimal level of the reference transducer for central venous pressure and pulmonary artery occlusion pressure monitoring in supine, prone, and sitting position. AB - To guarantee accurate measurement of central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP), proper positioning of a reference transducer is a prerequisite. We investigated ideal transducer levels in supine, prone, and sitting position in adults. Chest computed tomography images of 113 patients, taken in supine or prone position were reviewed. For supine position, distances between the back and the uppermost blood level of both atria and their ratios to the largest anteroposterior (AP) diameter of thorax were calculated. For prone position, same distances and ratios were calculated from the anterior chest. For sitting position, distances between the mid-sternoclavicular joint and the most cephalad blood level of both atria and their ratios to the sternal length were calculated. The ratio of the uppermost blood level of right atrium (RA) and left atrium (LA) to the largest AP diameter of thorax was 0.81 +/- 0.04 and 0.59 +/- 0.03 from the back in supine position. That calculated from the anterior chest in prone position was 0.54 +/- 0.03 and 0.46 +/- 0.03. The ratio of the most cephalad blood level of RA and LA to the sternal length was 0.70 +/- 0.10 and 0.68 +/- 0.09 from the mid-sternoclavicular joint in sitting position, which corresponded to the upper border of 4th rib. Optimal CVP transducer levels are at four-fifths of the AP diameter of thorax in supine position, at a half of that in prone position, and at upper border of the 4th sternochondral joint in sitting position. PAOP transducer levels are similar in prone and sitting position, except for supine position which is at three-fifths of the AP diameter of thorax. PMID- 27001385 TI - Transport and uptake effects of marine complex lipid liposomes in small intestinal epithelial cell models. AB - Nowadays, marine complex lipids, including starfish phospholipids (SFP) and cerebrosides (SFC) separated from Asterias amurensis as well as sea cucumber phospholipids (SCP) and cerebrosides (SCC) isolated from Cucumaria frondosa, have received much attention because of their potent biological activities. However, little information is known on the transport and uptake of these lipids in liposome forms in small intestinal cells. Therefore, this study was undertaken to investigate the effects of these complex lipid liposomes on transport and uptake in Caco-2 and M cell monolayer models. The results revealed that SFP and SCP contained 42% and 47.9% eicosapentaenoic acid (EPA), respectively. The average particle sizes of liposomes prepared in this study were from 169 to 189 nm. We found that the transport of the liposomes across the M cell monolayer model was much higher than the Caco-2 cell monolayer model. The liposomes consisting of SFP or SCP showed significantly higher transport and uptake than soy phospholipid (soy-PL) liposomes in both Caco-2 and M cell monolayer models. Our results also exhibited that treatment with 1 mM liposomes composed of SFP or SCP for 3 h tended to increase the EPA content in phospholipid fractions of both differentiated Caco-2 and M cells. Moreover, it was also found that the hybrid liposomes consisting of SFP/SFC/cholesterol (Chol) revealed higher transport and uptake across the M cell monolayer in comparison with other liposomes. Furthermore, treatment with SFP/SFC/Chol liposomes could notably decrease the trans-epithelial electrical resistance (TEER) values of Caco-2 and M cell monolayers. The present data also showed that the cell viability of differentiated Caco-2 and M cells was not affected after the treatment with marine complex lipids or soy-PL liposomes. Based on the data in this study, it was suggested that marine complex lipid liposomes exhibit prominent transport and uptake in small intestinal epithelial cell models. PMID- 27001386 TI - The Advantage of Synthetic MRI for the Visualization of Early White Matter Change in an Infant with Sturge-Weber Syndrome. PMID- 27001387 TI - Hepatic Amyloidosis with an Extremely High Stiffness Value on Magnetic Resonance Elastography. PMID- 27001388 TI - MR Imaging of Uterine Epithelioid Trophoblastic Tumor: A Case Report. AB - Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic neoplasm of chorionic-type intermediate trophoblasts, and it is most frequently located in the lower uterine segment and endocervix. Due to the epithelial-growth pattern with geographic necrosis exhibited by the neoplastic cells, ETT is commonly confused, both clinically and pathologically, with squamous cell carcinoma. Although there have been no previous reports of ETT focusing on computed tomography (CT) or magnetic resonance imaging (MRI) findings, we report a case of uterine ETT with special attention to the MRI findings referring to the pathological findings and MR images of previous reports. A 42-year-old Japanese woman (gravid 1, para 1) presented with uterus enlargement during screening, and complained of recent-onset lower abdominal pain. The MRI showed a solid tumor throughout the entire myometrium of the lower uterine segment, with the hemorrhagic cystic portion extending to the posterior subserosal space. Following hysterectomy, the final pathological diagnosis was ETT. An ETT is essentially a solid tumor composed of intermediate trophoblasts that exhibit an epithelial-like growth pattern and contain geographic necrosis with calcification. In our case, MRI revealed a non-specific-intensity solid tumor in the lower uterine segment with massive necrosis and hemorrhage extending to the subserosa. While it is difficult to distinguish between ETT and uterine carcinomas, recognition of certain tumor shapes and necrosis could enable more accurate diagnosis before treatment. PMID- 27001389 TI - "Sun Ray" Appearance in a Case of Cardiac Angiosarcoma: A Comparison of MRI and PET/CT. AB - Our article reports a case of a 35-year-old man with cardiac mass, who underwent a wide range of imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). Contrast enhanced MRI images revealed "sun ray" pattern in the mass. Final histopathological diagnosis of angiosarcoma was confirmed during autopsy. To our knowledge, our case is the second direct observation of this MRI diagnostic pattern and the first one that allows a comparison with PET/CT findings. PMID- 27001390 TI - Doppler Ultrasound Triggering for Cardiovascular MRI at 3T in a Healthy Volunteer Study. AB - PURPOSE: Electrocardiogram (ECG) triggering for cardiac magnetic resonance (CMR) may be influenced by electromagnetic interferences with increasing magnetic field strength. The aim of this study was to evaluate the performance of Doppler ultrasound (DUS) as an alternative trigger technique for CMR in comparison to ECG and pulse oximetry (POX) at 3T and using different sequence types. METHODS: Balanced turbo field echo two-dimensional (2D) short axis cine CMR and 2D phase contrast angiography of the ascending aorta was performed in 11 healthy volunteers at 3T using ECG, DUS, and POX for cardiac triggering. DUS and POX triggering were compared to the reference standard of ECG in terms of trigger quality (trigger detection and temporal variability), image quality [endocardial blurring (EB)], and functional measurements [left ventricular (LV) volumetry and aortic blood flow velocimetry]. RESULTS: Trigger signal detection and temporal variability did not differ significantly between ECG/DUS (I = 0.6) and ECG/POX (P = 0.4). Averaged EB was similar for ECG, DUS, and POX (pECG/DUS = 0.4, pECG/POX = 0.9). Diastolic EB was significantly decreased for DUS in comparison to ECG (P = 0.02) and POX (P = 0.04). The LV function assessment and aortic blood flow were not significantly different. CONCLUSION: This study demonstrated the feasibility of DUS for gating human CMR at 3T. The magnetohydrodynamic effect did not significantly disturb ECG triggering in this small healthy volunteer study. DUS showed a significant improvement in diastolic EB but could not be identified as a superior trigger method. The potential benefit of DUS has to be evaluated in a larger clinical patient population. PMID- 27001391 TI - Volume of Interest Analysis of Spatially Normalized PRESTO Imaging to Differentiate between Parkinson Disease and Atypical Parkinsonian Syndrome. AB - PURPOSE: Various magnetic resonance imaging (MRI) techniques including T2* weighted imaging, susceptibility-weighted imaging, and MR relaxometry had been performed to evaluate different patterns of brain iron depositions in Parkinsonian syndrome. The aim of the present study was to evaluate the diagnostic value of a volume of interest (VOI) analysis on the principles of echo shifting with a train of observations (PRESTO) imaging using the statistical parametric mapping (SPM) 8 and the WFU PickAtlas program for the diagnosis of Parkinsonian syndrome.,Methods: Fifty subjects, including 13 with the Parkinsonian variant of multiple system atrophy (MSA-P), 12 with progressive supranuclear palsy (PSP), 12 with Parkinson's disease (PD) and 13 controls were evaluated in this study. After the spatial normalization of PRESTO images on SPM8, the WFU PickAtlas program was performed to create target VOIs in the putamen, red nucleus, substantia nigra, subthalamic nucleus, and dentate nucleus. The signal intensity ratio (SIR) was calculated by normalizing the signal of each VOI to that of the cerebrospinal fluid space. These SIRs were used as determinants in receiver operating characteristic (ROC) analyses. RESULTS: SIR of the putamen was significantly lower in MSA-P than in PSP (P = 0.0051) and controls (P = 0.0004). In contrast, SIR of the red nucleus was significantly lower in PSP than in MSA-P (P = 0.0003), PD (P = 0.0029), and controls (P = 0.0011). In ROC analyses, SIR of the putamen exhibited the highest areas under the curves (AUCs) of 0.83 (vs. PSP) and 0.91 (vs. controls) in the diagnosis of MSA-P. On the other hand, SIR of the red nucleus exhibited the highest AUCs of 0.87 (vs. MSA-P), 0.90 (vs. PD), and 0.89 (vs. controls) in the diagnosis of PSP. CONCLUSIONS: The VOI analysis based on spatially normalized PRESTO images may be useful for depicting hypointensity, indicative of abnormal iron depositions, of the putamen and red nucleus in the diagnosis of MSA-P and PSP. PMID- 27001392 TI - Breath-holding during the Calibration Scan Improves the Reproducibility of Parallel Transmission at 7T for Human Brain. AB - PURPOSE: The B0 and B1+ maps required for calculation of the radiofrequency (RF) pulse of parallel transmission (pTx) are obtained in calibration scans; however, they may be affected by respiratory motion. We aimed to compare the reproducibility of B0 and B1+ maps and gradient echo (GRE) images of the brain scanned with pTx at 7T between free-breathing (FB) and breath-holding (BH) conditions during the calibration scan. METHODS: Nine healthy volunteers were scanned by 7T MRI using a two-channel quadrature head coil. In the pTx calibration scans performed with FB and BH, the B0 map was obtained from two different TE images and the B1+ map was calculated by the Bloch-Siegert method. A GRE image (gradient-recalled-acquisition in steady state) was also obtained with RF shimming and RF design of pTx with spoke method, as well as quadrature transmission (qTx). All the scans were repeated over five sessions. The reproducibility of the B0 and B1+ maps and GRE image was evaluated with region-of interest measurements using inter-session standard deviation (SD) and coefficient of variation (CV) values. Intensity homogeneity of GRE images was also assessed with in-plane CV. RESULTS: Inter-session SDs of B0 and B1+ maps were significantly smaller in BH (P < 0.01). Inter-session CVs of GRE images were significantly smaller in qTx than BH and FB (P < 0.01, both); however, the CVs of BH were significantly smaller (P < 0.01). In-plane CVs of FB and BH with RF shimming were not significantly different with qTx; however, CVs of FB and BH with RF design were significantly smaller than those of qTx (P < 0.05 and P < 0.01, respectively). CONCLUSION: BH could improve the reproducibility of B0 and B1+ maps in pTx calibration scans and GRE images. These results might facilitate the development of pTx in human brain at 7T. PMID- 27001393 TI - Arterial Spin-labeling in Central Nervous System Infection. AB - PURPOSE: To investigate the characteristics of arterial spin-labeling magnetic resonance imaging (ASL-MRI) in central nervous system (CNS) infection. METHODS: Thirty-two patients with CNS infections underwent a pulsed ASL-MRI. The findings on ASL-MRI were retrospectively assessed for the pathogens as well as each of the following four pathology classified based on conventional MRI findings: non purulent parenchymal involvement, meningeal involvement, abscess formation, and ventricular involvement. RESULTS: Among the 17 patients with non-purulent parenchymal involvement, ASL-MRI revealed high perfusion in 8 patients (47%) and low perfusion 1 patient (6%). Especially, four of five patients (80%) with definite or suspected herpes simplex virus (HSV) infection showed high perfusion on ASL-MRI. Seventeen of 22 patients (77%) with meningeal involvement showed high perfusion along the cerebral sulci irrespective of the pathogens. Meanwhile, 4 of 16 lesions (25%) with abscess formation showed low perfusion and one of six patients (17%) with ventricular involvement had high perfusion. CONCLUSIONS: The characteristics of ASL-MRI in CNS infections were clearly delineated. ASL-MRI could be helpful for monitoring the brain function in CNS infections noninvasively. PMID- 27001394 TI - Tmax Determined Using a Bayesian Estimation Deconvolution Algorithm Applied to Bolus Tracking Perfusion Imaging: A Digital Phantom Validation Study. AB - PURPOSE: The Bayesian estimation algorithm improves the precision of bolus tracking perfusion imaging. However, this algorithm cannot directly calculate Tmax, the time scale widely used to identify ischemic penumbra, because Tmax is a non-physiological, artificial index that reflects the tracer arrival delay (TD) and other parameters. We calculated Tmax from the TD and mean transit time (MTT) obtained by the Bayesian algorithm and determined its accuracy in comparison with Tmax obtained by singular value decomposition (SVD) algorithms. METHODS: The TD and MTT maps were generated by the Bayesian algorithm applied to digital phantoms with time-concentration curves that reflected a range of values for various perfusion metrics using a global arterial input function. Tmax was calculated from the TD and MTT using constants obtained by a linear least-squares fit to Tmax obtained from the two SVD algorithms that showed the best benchmarks in a previous study. Correlations between the Tmax values obtained by the Bayesian and SVD methods were examined. RESULTS: The Bayesian algorithm yielded accurate TD and MTT values relative to the true values of the digital phantom. Tmax calculated from the TD and MTT values with the least-squares fit constants showed excellent correlation (Pearson's correlation coefficient = 0.99) and agreement (intraclass correlation coefficient = 0.99) with Tmax obtained from SVD algorithms. CONCLUSIONS: Quantitative analyses of Tmax values calculated from Bayesian-estimation algorithm-derived TD and MTT from a digital phantom correlated and agreed well with Tmax values determined using SVD algorithms. PMID- 27001395 TI - Visualization of Middle Ear Ossicles in Elder Subjects with Ultra-short Echo Time MR Imaging. AB - PURPOSE: To evaluate the visualization of middle ear ossicles by ultra-short echo time magnetic resonance (MR) imaging at 3T in subjects over 50 years old. MATERIALS AND METHODS: Sixty ears from 30 elder patients that underwent surgical or interventional treatment for neurovascular diseases were included (ages: 50 82, median age: 65; 10 men, 20 women). Patients received follow-up MR imaging including routine T1- and T2-weighted images, time-of-flight MR angiography, and ultra-short echo time imaging (PETRA, pointwise encoding time reduction with radial acquisition). All patients underwent computed tomography (CT) angiography before treatment. Thin-section source CT images were correlated with PETRA images. Scan parameters for PETRA were: TR 3.13, TE 0.07, flip angle 6 degrees, 0.83 * 0.83 * 0.83 mm resolution, 3 min 43 s scan time. Two radiologists retrospectively evaluated the visibility of each ossicular structure as positive or negative using PETRA images. The structures evaluated included the head of the malleus, manubrium of the malleus, body of the incus, long process of the incus, and the stapes. Signal intensity of the ossicles was classified as: between labyrinthine fluid and air, similar to labyrinthine fluid, between labyrinthine fluid and cerebellar parenchyma, or higher than cerebellar parenchyma. RESULTS: In all ears, the body of the incus was visible. The head of the malleus was visualized in 36/60 ears. The manubrium of the malleus and long process of the incus was visualized in 1/60 and 4/60 ears, respectively. The stapes were not visualized in any ear. Signal intensity of the visible structures was between labyrinthine fluid and air in all ears. CONCLUSION: The body of the incus was consistently visualized with intensity between air and labyrinthine fluid on PETRA images in aged subjects. Poor visualization of the manubrium of the malleus, long process of the incus, and the stapes limits clinical significance of middle ear imaging with current PETRA methods. PMID- 27001396 TI - Simple Estimation of the Endolymphatic Volume Ratio after Intravenous Administration of a Single-dose of Gadolinium Contrast. AB - PURPOSE: To evaluate the feasibility of a simple estimation for the endolymphatic volume ratio (endolymph volume/total lymph volume = %ELvolume) from an area ratio obtained from only one slice (%EL1slice) or from three slices (%EL3slices). The %ELvolume, calculated from a time-consuming measurement on all magnetic resonance (MR) slices, was compared to the %EL1slice and the %EL3slices. METHODS: In 40 ears of 20 patients with a clinical suspicion of endolymphatic hydrops, MR imaging was performed 4 hours after intravenous administration of a single dose of gadolinium-based contrast material (IV-SD-GBCM). Using previously reported HYDROPS2-Mi2 MR imaging, the %ELvolume values in the cochlea and the vestibule were measured separately by two observers. The correlations between the %EL1slice or the %EL3slices and the %ELvolume values were evaluated. RESULTS: A strong linear correlation was observed between the %ELvolume and the %EL3slices or the %EL1slice in the cochlea. The Pearson correlation coefficient (r) was 0.968 (3 slices) and 0.965 (1 slice) for observer A, and 0.968 (3 slices) and 0.964 (1 slice) for observer B (P < 0.001, for all). A strong linear correlation was also observed between the %ELvolume and the %EL3slices or the %EL1slice in the vestibule. The Pearson correlation coefficient (r) was 0.980 (3 slices) and 0.953 (1 slice) for observer A, and 0.979 (3 slices) and 0.952 (1 slice) for observer B (P < 0.001, for all). The high intra-class correlation coefficients (0.991-0.997) between the endolymph volume ratios by two observers were observed in both the cochlea and the vestibule for values of the %ELvolume, the %EL3slices and the %EL1slice. CONCLUSION: The %ELvolume might be easily estimated from the %EL3slices or the %EL1slice. PMID- 27001397 TI - Balanced Turbo Field Echo with Extended k-space Sampling: A Fast Technique for the Thoracic Ductography. AB - We evaluated the visibility of the thoracic duct by fast balanced turbo field echo with extended k-space sampling (bTFEe). The thoracic duct of 10 healthy volunteers was scanned by bTFEe using a 1.5-T magnetic resonance imaging (MRI), which was acquired in approximately 2 minutes. Three-dimensional (3D) turbo spin echo (TSE) was obtained for comparison. The thoracic duct including draining location of the venous system was overall well visualized on bTFEe, compared to TSE. PMID- 27001398 TI - Echo-Planar Imaging for a 9.4 Tesla Vertical-Bore Superconducting Magnet Using an Unshielded Gradient Coil. AB - Echo-planar imaging (EPI) sequences were developed for a 9.4 Tesla vertical standard bore (~54 mm) superconducting magnet using an unshielded gradient coil optimized for live mice imaging and a data correction technique with reference scans. Because EPI requires fast switching of intense magnetic field gradients, eddy currents were induced in the surrounding metallic materials, e.g., the room temperature bore, and this produced serious artifacts on the EPI images. We solved the problem using an unshielded gradient coil set of proper size (outer diameter = 39 mm, inner diameter = 32 mm) with time control of the current rise and reference scans. The obtained EPI images of a phantom and a plant sample were almost artifact-free and demonstrated the promise of our approach. PMID- 27001400 TI - Measurement of Strain in Cardiac Myocytes at Micrometer Scale Based on Rapid Scanning Confocal Microscopy and Non-Rigid Image Registration. AB - Measurement of cell shortening is an important technique for assessment of physiology and pathophysiology of cardiac myocytes. Many types of heart disease are associated with decreased myocyte shortening, which is commonly caused by structural and functional remodeling. Here, we present a new approach for local measurement of 2-dimensional strain within cells at high spatial resolution. The approach applies non-rigid image registration to quantify local displacements and Cauchy strain in images of cells undergoing contraction. We extensively evaluated the approach using synthetic cell images and image sequences from rapid scanning confocal microscopy of fluorescently labeled isolated myocytes from the left ventricle of normal and diseased canine heart. Application of the approach yielded a comprehensive description of cellular strain including novel measurements of transverse strain and spatial heterogeneity of strain. Quantitative comparison with manual measurements of strain in image sequences indicated reliability of the developed approach. We suggest that the developed approach provides researchers with a novel tool to investigate contractility of cardiac myocytes at subcellular scale. In contrast to previously introduced methods for measuring cell shorting, the developed approach provides comprehensive information on the spatio-temporal distribution of 2-dimensional strain at micrometer scale. PMID- 27001401 TI - US researchers blocked from testing Cuban drug. PMID- 27001399 TI - Evaluation of Direct Collocation Optimal Control Problem Formulations for Solving the Muscle Redundancy Problem. AB - Estimation of muscle forces during motion involves solving an indeterminate problem (more unknown muscle forces than joint moment constraints), frequently via optimization methods. When the dynamics of muscle activation and contraction are modeled for consistency with muscle physiology, the resulting optimization problem is dynamic and challenging to solve. This study sought to identify a robust and computationally efficient formulation for solving these dynamic optimization problems using direct collocation optimal control methods. Four problem formulations were investigated for walking based on both a two and three dimensional model. Formulations differed in the use of either an explicit or implicit representation of contraction dynamics with either muscle length or tendon force as a state variable. The implicit representations introduced additional controls defined as the time derivatives of the states, allowing the nonlinear equations describing contraction dynamics to be imposed as algebraic path constraints, simplifying their evaluation. Problem formulation affected computational speed and robustness to the initial guess. The formulation that used explicit contraction dynamics with muscle length as a state failed to converge in most cases. In contrast, the two formulations that used implicit contraction dynamics converged to an optimal solution in all cases for all initial guesses, with tendon force as a state generally being the fastest. Future work should focus on comparing the present approach to other approaches for computing muscle forces. The present approach lacks some of the major limitations of established methods such as static optimization and computed muscle control while remaining computationally efficient. PMID- 27001402 TI - Sex differences in substance use disorders: focus on side effects. AB - Although sex differences in several aspects of substance use disorders (SUDs) have been identified, less is known about the importance of possible sex differences in side effects induced by substances of abuse or by medications used to treat SUDs. In the SUD field, the perception of certain subjective effects are actively sought, while all other manifestations might operationally be considered side effects. This article was aimed at reviewing sex differences in side effects induced by alcohol, nicotine, heroin, marijuana and cocaine and by medications approved for alcohol, nicotine and heroin use disorders. A large body of evidence suggests that women are at higher risk of alcohol-induced injury, liver disease, cardiomyopathy, myopathy, brain damages and mortality. The risk of tobacco induced coronary heart disease, lung disease and health problems is higher for women than for men. Women also experience greater exposure to side effects induced by heroin, marijuana and cocaine. In addition, women appear to be more vulnerable to the side effects induced by medications used to treat SUDs. Patients with SUDs should be advised that the risk of developing health problems may be higher for women than for men after consumption of the same amount of substances of abuse. Doses of medications for SUD women should be adjusted at least according to body weight. The sex differences observed also indicate an urgent need to recruit adequate numbers of female subjects in pre-clinical and clinical studies to improve our knowledge about SUDs in women. PMID- 27001403 TI - Development of SSR Markers Linked to Low Hydrocyanic Acid Content in Sorghum Sudan Grass Hybrid Based on BSA Method. AB - Sorghum-Sudan grass hybrid containing high hydrocyanic acid content can cause hydrocyanic acid poisoning to the livestock and limit the popularization of this forage crop. Molecular markers associated with low hydrocyanic acid content can speed up the process of identification of genotypes with low hydrocyanic acid content. In the present study, 11 polymorphic SSR primers were screened and used for bulked segregant analysis and single marker analysis. Three SSR markers Xtxp7230, Xtxp7375 and Bnlg667960 associated with low hydrocyanic acid content were rapidly identified by BSA. In single marker analysis, six markers Xtxp7230, Xtxp7375, Bnlg667960, Xtxp67-11, Xtxp295-7 and Xtxp12-9 were linked to low hydrocyanic acid content, which explained the proportion of phenotypic variation from 7.6 % to 41.2 %. The markers identified by BSA were also verified by single marker analysis. The three SSR marker bands were then cloned and sequenced for sequence homology analysis in NCBI. It is the first report on the development of molecular markers associated with low hydrocyanic acid content in sorghum- Sudan grass hybrid. These markers will be useful for genetic improvement of low hydrocyanic acid sorghum-Sudan grass hybrid by marker-assisted breeding. PMID- 27001404 TI - Isolation and Functional Characterization of a Novel Gene Encoding a Dehydration Responsive Element Binding Transcription Factor from Populus euphratica. AB - Dehydration responsive element binding (DREB) transcription factors (TFs) play a key role in regulating abiotic stress related genes. A new gene (PeDREB2b) encoding an unidentified DRE-binding protein was isolated from 20% PEG6000 treated Populus euphratica Oliv. seedlings by RT-PCR and RACE. Full length of PeDREB2b cDNA was 1110 bp, and an ORF of 870 bp, which encoded 289-amino-acids polypeptide, were included. The deduced amino acid sequence analysis revealed that this protein was a putative AP2/EREBP transcription factor with a conserved AP2/EREBP domain of 64 amino acids and a potential nuclear localization signal (NLS). Based on phylogenetic characterization, PeDREB2b was classified as a member of A-5 group belonged to the DREB family. The PeDREB2b gene is induced by salinization, low temperature, drought and phytohormones GA3, NAA and 6BA, but not by ABA treatment. The fact that the product of PeDREB2b as a DREB transcription factor was verified in our further experiment: the nuclear localization of the gene when it was expressed transiently as a GFP fusion in onion epidermal cells. In addition, PeDREB2b was capable of activating reporter gene expression. To study the salt and drought stress responses for PeDREB2b transgenic Arabidopsis thaliana in detail, integrated physiological, biochemical and genetic approach methods were used. Results indicated that the PeDREB2b gene was over-expressed under stress-inducible rd29A promotor in transgenic plants alleviates the adverse effects of environmental stresses. PMID- 27001405 TI - Research on Root Responses to Pb and Zn Combined Stress of Carex putuoshan. AB - Pb hyper-accumulated Carex putuoshan was taken as experimental material and subjected to combined stress of Pb and Zn. The differential expression of proteins in their roots were analyzed by Proteomic Approach. The protein that was directly involved in the cellular defense under the Pb and Zn combined stress was separated, and expression of those genes was analyzed with Carex Evergold as control. The results were obtained by MALDI-TOF/MS analysis. After applying Pb and Zn combined stress, the expression of 9 protein spots (including 7 different proteins, 2 identical proteins, 1 unknown protein) in Carex putuoshan root was found to be significantly up-regulated. Five proteins were obtained from the 9 proteins related to carbohydrate metabolism, including malate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, frutose-1,6-bisphosphate aldolase, enolase, and 6- phosphogluconate dehydrogenase. Two proteins were related to protein biosynthesis, including isoflavone reductase and phytochelatin synthase (PCS). From these proteins, the most important protein is PCS, which is a key enzyme in the synthesis of phytochelatins (PCs) and plays an important role in chelation. It is directly involved in cellular defense under Pb and Zn stress. After Pb and Zn combined stress, the CpPCS in Carex putuoshan was cloned. The full length of cDNA is 1461 bps, and it encodes 486 amino acids with molecular weight of 53.86 kD and pI value of 6.12. Two typical phytochelatin synthase subfamily domains constitute CpPCS protein, which includes three adjacent Cys-Cys elements in the C-terminal region. Phylogenetic analysis of PCS proteins from different species showed that it had the closest relationship with the Oryza sativa and Triticum aestivum. Real-time quantitative PCR analysis indicated that CpPCS and CePCS (Carex Evergold) genes were expressed in the root. The CpPCS and CePCS genes were up-regulated by Pb and Zn treatments. The expression of CpPCS was higher than that of CePCS under the same condition. The study found that CpPCS expression was increased by Pb and Zn stress in the Carex putuoshan enrichment process of Pb, which lead to high expression of PCS protein. CpPCS improved the accumulation ability and resistance of Carex putuoshan to heavy metals with the expression level of glucose metabolism related proteins increasing after Pb and Zn stress. PMID- 27001406 TI - Overexpression of the Lotus corniculatus Soloist Gene LcAP2/ERF107 Enhances Tolerance to Salt Stress. AB - The AP2/ERF play a key role in multiple stress responses in plants. we here report a novel salt stress-related gene, LcAP2/ERF107 that encodes an AP2/ERF protein in Lotus corniculatus cultivar Leo. LcAP2/ERF107 was classified into the soloist subfamiliy based on phylogenetic relationship. The transcription of LcAP2/ERF107 were strongly induced by salt and other phytohormones (ABA, ACC, MeJA). A subcellular localization experiment indicated that LcAP2/ERF107 is a nuclear protein that activates transcription. LcAP2/ERF107 overexpression in Arabidopsis resulted in pleiotropic phenotypes, including higher seed germination rate and transgenic plants with enhanced tolerance to salt stress. Further, under salt tolerance the transgenic lines elevated the relative moisture content; however, the relative electrolyte leakage was lower than in control plants. The expression levels of indicative genes RD22, RD29A, LEA4-5, P5CS1 and P5CS2 were found to be increased in the transgenic plants compared with the WT plants. These results indicated that LcAP2/ERF107 play an important role in the responses of plant to salt stress. PMID- 27001407 TI - Investigating the disposal of expired and unused medication in Riyadh, Saudi Arabia: a cross-sectional study. AB - Background Improper disposal of medication has several possible consequences such as childhood poisoning, environmental pollution, a negative impact on wildlife, and antibiotic resistance. The number of studies conducted to characterize pharmaceutical disposal practices is limited, particularly in the Middle East. Objective The aim of this cross-sectional study was to examine the behaviour of individuals with respect to the disposal of expired and unused medications. Furthermore, we aimed to identify the best methods of education regarding appropriate, safe disposal of medication. Setting The study was carried out in King Khalid University Hospital (KKUH), and King Saud University (KSU), during a 3-month period from February 2015 to April 2015. Method Twelve hundred patients were randomly selected from KKUH and KSU. Participants were invited to complete paper-based questionnaire with self enumeration. Pilot testing was conducted and involved 50 randomly selected participants. Main outcome measures The proportion of expired medications present in the home and their therapeutic groups, disposal methods of expired and unused medications, and preferred educational methods regarding safe and proper disposing of medications. Results A substantial proportion (79.15 %) of respondents disposed of unwanted medication via household waste, while a small proportion (1.70 %) returned unwanted medication to a pharmacy. Although currently practised disposal methods are undoubtedly unsuitable, 70.20 % of respondents considered finding appropriate, safe methods via which to dispose of unwanted medication their responsibility, and 78.6 % expressed an interest in receiving information concerning the correct disposal of unwanted medication. Conclusion We have demonstrated that a low percentage of respondents have ever received information regarding correct medication disposal. Moreover, the results have shown that over half of the respondents store antibiotics in their households. Additionally, respondents weren't aware of the consequences of keeping expired medication at home. It is quite clear that the awareness of proper and safe drug disposal among the Saudi population is quite low making it a priority of concerned authorities to implement educational programs. PMID- 27001408 TI - The pharmacokinetics of ampicillin-sulbactam in anuric patients: dosing optimization for prophylaxis during cardiovascular surgery. AB - Background The administration of antibiotic prophylaxis during cardiothoracic surgery can reduce the rate of surgical site infections. Trials of cardiothoracic antibiotic prophylaxis have found it to be beneficial in preventing postoperative wound infections. Objective To determine the more appropriate timing of repeated doses of ampicillin-sulbactam to maintain adequate antibiotic concentrations during cardiovascular surgery in anuric patients. Method Five adult anuric dialysis patients who received ampicillin-sulbactam during cardiovascular surgery at Kagoshima University Hospital, the total plasma concentrations of ampicillin and sulbactam were monitored after ampicillin (1 g)-sulbactam (0.5 g) administration. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin and sulbactam. Results The mean values for the volume of distribution, total clearance, elimination rate constant and the elimination half-life for ampicillin were 8.9 +/- 2.4 L, 1.69 +/- 0.93 L/h, 0.180 +/- 0.059 h(-1) and 4.23 +/- 1.48 h, respectively. The pharmacokinetic parameters were similar to those of sulbactam. When ampicillin (1 g)-sulbactam (0.5 g) was intravenously administered at 8, 12 and 24 h intervals, the predicted free trough plasma concentrations of ampicillin were 28.72, 12.06 and 1.25 MUg/mL, respectively. Conclusion We suggest that ampicillin (1 g)-sulbactam (0.5 g) should be intravenously administered every 12 h in order to maintain a free ampicillin concentration of more than 12 MUg/mL in anuric patients during cardiovascular surgery. PMID- 27001409 TI - Cost-effectiveness of screening strategies to detect heart failure in patients with type 2 diabetes. AB - BACKGROUND: Heart failure (HF), especially with preserved ejection fraction (HFpEF) is common in older patients with type 2 diabetes (T2DM), but often not recognized. Early HF detection in older T2DM patients may be worthwhile because treatment may be initiated in an early stage, with clear beneficial treatment in those with reduced ejection fraction (HFrEF), but without clear prognostic beneficial treatment in those with HFpEF. Because both types of HF may be uncovered in older T2DM, screening may improve health outcomes at acceptable costs. We assessed the cost-effectiveness of five screening strategies in patients with T2DM aged 60 years or over. METHODS: We built a Markov model with a lifetime horizon based on the prognostic results from our screening study of 581 patients with T2DM, extended with evidence from literature. Cost-effectiveness was calculated from a Dutch healthcare perspective as additional costs (Euros) per additional quality-adjusted life-year (QALY) gained. We performed probabilistic sensitivity analysis to assess robustness of these outcomes. Scenario analyses were performed to assess the influence of the availability of effective treatment of heart failure with preserved ejection fraction. RESULTS: For willingness to pay values in the range of ?6050/QALY-?31,000/QALY for men and ?6300/QALY-?42,000/QALY for women, screening-based checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms had the highest probability of being cost-effective. For higher willingness-to-pay values, direct echocardiography was the preferred screening strategy. Cost-effectiveness of all screening strategies improved with the increase in effectiveness of treatment for HFpEF. CONCLUSIONS: Screening for HF in older community-dwelling patients with T2DM is cost-effective at the commonly used willingness-to-pay threshold of ?20.000/QALY by checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms. The simplicity of such a strategy makes it feasible for implementation in existing primary care diabetes management programs. PMID- 27001410 TI - Studying the effects of asymmetry on the bending rigidity of lipid membranes formed by microfluidics. AB - In this article we detail a robust high-throughput microfluidic platform capable of fabricating either symmetric or asymmetric giant unilamellar vesicles (GUVs) and characterise the mechanical properties of their membranes. PMID- 27001411 TI - An evaluation of nursing students' perceptions on the efficacy of high fidelity clinical simulation to enhance their confidence, understanding and competence in managing psychiatric emergencies. PMID- 27001412 TI - Coulomb blockade in monolayer MoS2 single electron transistor. AB - Substantial effort has been dedicated to understand the intrinsic electronic properties of molybdenum disulfide (MoS2). However, electron transport study on monolayer MoS2 has been challenging to date, especially at low temperatures due to large metal/semiconductor junction barriers. Herein, we report the fabrication and characterization of the monolayer MoS2 single-electron transistor. High performance devices are obtained through the use of low work function metal (zinc) contact and a rapid thermal annealing step. Coulomb blockade is observed at low temperatures and is attributed to single-electron tunneling via two tunnel junction barriers. The nature of Coulomb blockade is also investigated by temperature-dependent conductance oscillation measurement. Our results hold promise for the study of novel quantum transport phenomena in 2D semiconducting atomic layer crystals. PMID- 27001413 TI - Recalcitrant Livedoid Vasculopathy Associated with Hyperhomocysteinaemia Responding to Folic Acid and Vitamins B6/B12 Supplementation. PMID- 27001414 TI - Anti-migratory activity of marine alkaloid monanchocidin A - proteomics-based discovery and confirmation. AB - Monanchocidin A (MonA) is a novel marine alkaloid with promising anti-cancer properties. We recently demonstrated its high efficacy in human urogenital cancers including germ cell tumors. Here, we applied a global proteome screening approach to investigate molecular targets and biological processes affected by MonA in the human cisplatin-resistant germ cell cancer cell line NCCIT-R. Bioinformatical analysis of the proteomics data predicted an effect of MonA on cancer cell migration. Thus, proteins known to be involved in cancer cell migration and invasion were chosen for further validation. The protein alterations identified by proteomics resulted from both, regulation of the total protein expression and post-transcriptional modifications. Among others, regulation of an isoform of vimentin, up-regulation of multiple apolipoprotein E isoforms, and inhibition of hypusination of eukaryotic translation initiation factor 5A-1 were found upon treatment with MonA. Further functional analyses were performed and revealed decreased cell migration and colony formation of cancer cells treated with MonA at non-cytotoxic and non-antiproliferative concentrations. This work provides further insights into the molecular mechanisms behind MonA bioactivity. Furthermore, our research is exemplary for the ability of proteomics to predict drug targets and mode of action of natural anti-cancer agents. PMID- 27001415 TI - Selector-free resistive switching memory cell based on BiFeO3 nano-island showing high resistance ratio and nonlinearity factor. AB - Highly nonlinear bistable current-voltage (I-V) characteristics are necessary in order to realize high density resistive random access memory (ReRAM) devices that are compatible with cross-point stack structures. Up to now, such I-V characteristics have been achieved by introducing complex device structures consisting of selection elements (selectors) and memory elements which are connected in series. In this study, we report bipolar resistive switching (RS) behaviours of nano-crystalline BiFeO3 (BFO) nano-islands grown on Nb-doped SrTiO3 substrates, with large ON/OFF ratio of 4,420. In addition, the BFO nano-islands exhibit asymmetric I-V characteristics with high nonlinearity factor of 1,100 in a low resistance state. Such selector-free RS behaviours are enabled by the mosaic structures and pinned downward ferroelectric polarization in the BFO nano islands. The high resistance ratio and nonlinearity factor suggest that our BFO nano-islands can be extended to an N * N array of N = 3,740 corresponding to ~10(7) bits. Therefore, our BFO nano-island showing both high resistance ratio and nonlinearity factor offers a simple and promising building block of high density ReRAM. PMID- 27001416 TI - The neurotoxicity of DE-71: effects on neural development and impairment of serotonergic signaling in zebrafish larvae. AB - The underlying mechanism of polybrominated diphenyl ether (PBDE)-induced neurotoxicity is still a major concern due to its ubiquitous nature and persistence. Here, zebrafish embryos (2 h postfertilization, hpf) were exposed to different concentrations of the commercial PBDE mixture DE-71 (0-100 ug l-1 ) until 120 hpf, and the impact on neural development and serotonergic system was investigated. The in vivo results revealed significantly reduced transcription of genes involved in neurogenesis (fgf8, shha, wnt1), and contents of proteins in neuronal morphogenesis (myelin basic protein, synapsin IIa), suggesting an impairment of neural development in zebrafish embryos. Further results demonstrated a reduction of 5-hydroxytryptamine neuron and a dose-dependent decrease of whole-body serotonin levels, as well as the transcription of genes involved in serotonergic synthesis (tph1, tph2, trhr) and neurotransmission (serta/b, htr1aa/b). In addition, we predicted possible targets of PBDEs by molecular docking, and the results indicated that PBDE congeners showed high binding affinities with fibroblast growth factor 8 other than SHH and HTR1B. Taken together, this study demonstrated that PBDE exposure during embryogenesis could damage neural development and cause impairment of the serotonergic system as secondary effects in the zebrafish larvae. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001418 TI - A Single Excitation-Duplexed Imaging Strategy for Profiling Cell Surface Protein Specific Glycoforms. AB - This work develops a site-specific duplexed luminescence resonance energy transfer system on cell surface for simultaneous imaging of two kinds of monosaccharides on a specific protein by single near-infrared excitation. The single excitation-duplexed imaging system utilizes aptamer modified upconversion luminescent nanoparticles as an energy donor to target the protein, and two fluorescent dye acceptors to tag two kinds of cell surface monosaccharides by a dual metabolic labeling technique. Upon excitation at 980 nm, only the dyes linked to protein-specific glycans can be lit up by the donor by two parallel energy transfer processes, for in situ duplexed imaging of glycoforms on specific protein. Using MUC1 as the model, this strategy can visualize distinct glycoforms of MUC1 on various cell types and quantitatively track terminal monosaccharide pattern. This approach provides a versatile platform for profiling protein specific glycoforms, thus contributing to the study of the regulation mechanisms of protein functions by glycosylation. PMID- 27001417 TI - Functional Connectome before and following Temporal Lobectomy in Mesial Temporal Lobe Epilepsy. AB - As mesial temporal lobe epilepsy (mTLE) has been recognized as a network disorder, a longitudinal connectome investigation may shed new light on the understanding of the underlying pathophysiology related to distinct surgical outcomes. Resting-state functional MRI data was acquired from mTLE patients before (n = 37) and after (n = 24) anterior temporal lobectomy. According to surgical outcome, patients were classified as seizure-free (SF, n = 14) or non seizure-free (NSF, n = 10). First, we found higher network resilience to targeted attack on topologically central nodes in the SF group compared to the NSF group, preoperatively. Next, a two-way mixed analysis of variance with between-subject factor 'outcome' (SF vs. NSF) and within-subject factor 'treatment' (pre operation vs. post-operation) revealed divergent dynamic reorganization in nodal topological characteristics between groups, in the temporoparietal junction and its connection with the ventral prefrontal cortex. We also correlated the network damage score (caused by surgical resection) with postsurgical brain function, and found that the damage score negatively correlated with postoperative global and local parallel information processing. Taken together, dynamic connectomic architecture provides vital information for selecting surgical candidates and for understanding brain recovery mechanisms following epilepsy surgery. PMID- 27001419 TI - Identification and functional analysis of the L-ascorbate-specific enzyme II complex of the phosphotransferase system in Streptococcus mutans. AB - BACKGROUND: Streptococcus mutans is the primary etiological agent of human dental caries. It can metabolize a wide variety of carbohydrates and produce large amounts of organic acids that cause enamel demineralization. Phosphoenolpyruvate dependent sugar phosphotransferase system (PTS) plays an important role in carbohydrates uptake of S. mutans. The ptxA and ptxB genes in S. mutans encode putative enzyme IIA and enzyme IIB of the L-ascorbate-specific PTS. The aim of this study was to analyze the function of these proteins and understand the transcriptional regulatory mechanism. RESULTS: ptxA (-), ptxB (-), as well as ptxA (-) , ptxB (-) double-deletion mutants all had more extended lag phase and lower growth yield than wild-type strain UA159 when grown in the medium using L ascorbate as the sole carbon source. Acid production and acid killing assays showed that the absence of the ptxA and ptxB genes resulted in a reduction in the capacity for acidogenesis, and all three mutant strains did not survive an acid shock. According to biofilm and extracellular polysaccharides (EPS) formation analysis, all the mutant strains formed much less prolific biofilms with small amounts of EPS than wild-type UA159 when using L-ascorbate as the sole carbon source. Moreover, PCR analysis and quantitative real-time PCR revealed that sgaT, ptxA, ptxB, SMU.273, SMU.274 and SMU.275 appear to be parts of the same operon. The transcription levels of these genes were all elevated in the presence of L ascorbate, and the expression of ptxA gene decreased significantly once ptxB gene was knockout. CONCLUSIONS: The ptxA and ptxB genes are involved in the growth, aciduricity, acidogenesis, and formation of biofilms and EPS of S. mutans when L ascorbate is the sole carbon source. In addition, the expression of ptxA is regulated by ptxB. ptxA, ptxB, and the upstream gene sgaT, the downstream genes SMU.273, SMU.274 and SMU.275 appear to be parts of the same operon, and L ascorbate is a potential inducer of the operon. PMID- 27001420 TI - COMPARISON OF ULTRASOUND-GUIDED VS. STANDARD LANDMARK TECHNIQUES FOR TRAINING NOVICE OPERATORS IN PLACING NEEDLES INTO THE LUMBAR SUBARACHNOID SPACE OF CANINE CADAVERS. AB - The standard technique for placing a needle into the canine lumbar subarachnoid space is primarily based on palpation of anatomic landmarks and use of probing movements of the needle, however, this technique can be challenging for novice operators. The aim of the current observational, prospective, ex vivo, feasibility study was to compare ultrasound-guided vs. standard anatomic landmark approaches for novices performing needle placement into the lumbar subarachnoid space using dog cadavers. Eight experienced operators validated the canine cadaver model as usable for training landmark and ultrasound-guided needle placement into the lumbar subarachnoid space based on realistic anatomy and tissue consistency. With informed consent, 67 final year veterinary students were prospectively enrolled in the study. Students had no prior experience in needle placement into the lumbar subarachnoid space or use of ultrasound. Each student received a short theoretical training about each technique before the trial and then attempted blind landmark-guided and ultrasound-guided techniques on randomized canine cadavers. After having performed both procedures, the operators completed a self-evaluation questionnaire about their performance and self confidence. Total success rates for students were 48% and 77% for the landmark- and ultrasound-guided techniques, respectively. Ultrasound guidance significantly increased total success rate when compared to the landmark-guided technique and significantly reduced the number of attempts. With ultrasound guidance self confidence was improved, without bringing any significant change in duration of the needle placement procedure. Findings indicated that use of ultrasound guidance and cadavers are feasible methods for training novice operators in needle placement into the canine lumbar subarachnoid space. PMID- 27001421 TI - Augmentation of phosphate-induced osteo-/chondrogenic transformation of vascular smooth muscle cells by homoarginine. AB - AIMS: Reduced homoarginine plasma levels are associated with unfavourable cardiovascular outcome in chronic kidney disease (CKD). Cardiovascular events in CKD are fostered by vascular calcification, an active process promoted by hyperphosphatemia and involving osteo-/chondrogenic transformation of vascular smooth muscle cells (VSMCs). The present study explored the effect of homoarginine on phosphate-induced osteo-/chondrogenic signalling and vascular calcification. METHODS AND RESULTS: Experiments were performed in hyperphosphatemic klotho-hypomorphic mice (kl/kl), in subtotal nephrectomy and vitamin D3-overload mouse calcification models and in primary human aortic smooth muscle cells (HAoSMCs). As a result, plasma homoarginine levels were lower in kl/kl mice than in wild-type mice and in both genotypes significantly increased by lifelong treatment with homoarginine. Surprisingly, homoarginine treatment of kl/kl mice and of mice with renal failure after subtotal nephrectomy augmented vascular calcification and enhanced the transcript levels of plasminogen activator inhibitor 1 (Pai1) and of osteogenic markers Msx2, Cbfa1, and Alpl. Similarly, homoarginine treatment of HAoSMCs increased phosphate-induced calcium deposition, ALP activity, as well as PAI1, MSX2, CBFA1, and ALPL mRNA levels. Homoarginine alone up-regulated osteo-/chondrogenic signalling and indicators of oxidative stress in HAoSMCs. Furthermore, homoarginine reduced citrulline formation from arginine by nitric oxide (NO) synthase (NOS) isoforms. NO formation by NOS was reduced when using homoarginine as a substrate instead of arginine. The osteoinductive effects of homoarginine were mimicked by NOS inhibitor L-NAME and abolished by additional treatment with the NO donors DETA NONOate and PAPA-NONOate or the antioxidants TEMPOL and TIRON. Furthermore, homoarginine augmented vascular calcification and aortic osteo-/chondrogenic signalling in mice after vitamin D3-overload, effects reversed by the NO donor molsidomine. CONCLUSION: Homoarginine augments osteo-/chondrogenic transformation of VSMCs and vascular calcification, effects involving impaired NO formation from homoarginine. PMID- 27001422 TI - Cardiac salvage by tweaking with beta-3-adrenergic receptors. AB - Overstimulation of the orthosympathetic system leads to cardiovascular cell and tissue damage through prolonged activation of beta-1-2 adrenergic receptors (BARs). The more recent identification of the third isotype of BAR (B3AR) in cardiac myocytes and endothelial cells with a distinctive coupling and effect on cardiac function and remodelling introduced a new facet to this paradigm. In particular, B3AR is up-regulated in cardiac disease and less prone to homologous desensitization, which may reinforce its influence on the diseased myocardium. Mice with transgenic cardiac-specific expression of the human B3AR are protected from cardiac hypertrophy and fibrosis in response to neurohormonal stimulation. B3AR has also been implicated in cardiac protection after ischaemia-reperfusion and the benefits of exercise on the heart. Many of these salvage mechanisms are mediated by B3AR coupling to nitric oxide synthase (eNOS and nNOS) and downstream cGMP/protein kinase G signalling. Notably, B3AR exerts antioxidant protective effects on these and other signalling elements, which may subserve its protective properties in the setting of chronic heart failure. Additional vasorelaxing properties and paracrine NO-mediated signalling by B3AR in endothelium, together with systemic metabolic effects on beige/brown fat complete the pleiotropic protective properties of this new therapeutic target. PMID- 27001423 TI - Mechanistic insights into the first Lygus-active beta-pore forming protein. AB - The cotton pests Lygus hesperus and Lygus lineolaris can be controlled by expressing Cry51Aa2.834_16 in cotton. Insecticidal activity of pore-forming proteins is generally associated with damage to the midgut epithelium due to pores, and their biological specificity results from a set of key determinants including proteolytic activation and receptor binding. We conducted mechanistic studies to gain insight into how the first Lygus-active beta-pore forming protein variant functions. Biophysical characterization revealed that the full-length Cry51Aa2.834_16 was a stable dimer in solution, and when exposed to Lygus saliva or to trypsin, the protein underwent proteolytic cleavage at the C-terminus of each of the subunits, resulting in dissociation of the dimer to two separate monomers. The monomer showed tight binding to a specific protein in Lygus brush border membranes, and also formed a membrane-associated oligomeric complex both in vitro and in vivo. Chemically cross-linking the beta-hairpin to the Cry51Aa2.834_16 body rendered the protein inactive, but still competent to compete for binding sites with the native protein in vivo. Our study suggests that disassociation of the Cry51Aa2.834_16 dimer into monomeric units with unoccupied head-region and sterically unhindered beta-hairpin is required for brush border membrane binding, oligomerization, and the subsequent steps leading to insect mortality. PMID- 27001424 TI - Single-column purification of the tag-free, recombinant form of the neuronal calcium sensor protein, hippocalcin expressed in Escherichia coli. AB - Hippocalcin is a 193 aa protein that is a member of the neuronal calcium sensor protein family, whose functions are regulated by calcium. Mice that lack the function of this protein are compromised in the long term potentiation aspect of memory generation. Recently, mutations in the gene have been linked with dystonia in human. The protein has no intrinsic enzyme activity but is known to bind to variety of target proteins. Very little information is available on how the protein executes its critical role in signaling pathways, except that it is regulated by binding of calcium. Further delineation of its function requires large amounts of pure protein. In this report, we present a single-step purification procedure that yields high quantities of the bacterially expressed, recombinant protein. The procedure may be adapted to purify the protein from inclusion bodies or cytosol in its myristoylated or non-myristoylated forms. MALDI-MS (in source decay) analyses demonstrates that the myristoylation occurs at the glycine residue. The protein is also biologically active as measured through tryptophan fluorescence, mobility shift and guanylate cyclase activity assays. Thus, further analyses of hippocalcin, both structural and functional, need no longer be limited by protein availability. PMID- 27001425 TI - Effect of propofol and sevoflurane on the inflammatory response of patients undergoing craniotomy. AB - BACKGROUND: The purpose of this randomised, single-centre study was to prospectively investigate the impact of anaesthetic techniques for craniotomy on the release of cytokines IL-6, IL-8, IL-10, and to determine whether intravenous anaesthesia compared to inhalational anaesthesia attenuates the inflammatory response. METHODS: The study enroled 40 patients undergoing craniotomy, allocated into two equal groups to receive either sevoflurane (n = 20) or propofol (n = 20) in conjunction with remifentanil and rocuronium. The lungs were ventilated mechanically to maintain normocapnia. Remifentanil infusion was adjusted according to the degree of surgical manipulation and increased when mean arterial pressure and the heart rate increased by more than 30 % from baseline. The depth of anaesthesia was adjusted to maintain a bispectral index (BIS) of 40-60. Invasive haemodynamic monitoring was used. Serum levels of IL-6, IL-8 and IL-10 were measured before surgery and anaesthesia, during tumour removal, at the end of surgery, and at 24 and 48 h after surgery. Postoperative complications (pain, vomiting, changes in blood pressure, infection and pulmonary, cardiovascular and neurological events) were monitored during the first 15 days after surgery. RESULTS: Compared with patients anaesthetised with sevoflurane, patients who received propofol had higher levels of IL-10 (p = 0.0001) and lower IL-6/IL-10 concentration ratio during and at the end of surgery (p = 0.0001). Both groups showed only a minor response of IL- 8 during and at the end of the surgery (p = 0.57). CONCLUSIONS: Patients who received propofol had higher levels of IL-10 during surgery. Neither sevoflurane nor propofol had any significant impact on the occurrence of postoperative complications. Our findings should incite future studies to prove a potential medically important anti-inflammatory role of propofol in neuroanaesthesia. CLINICAL TRIAL REGISTRATION: Identified as NCT02229201 at www.clinicaltrials.gov. PMID- 27001426 TI - Retinoic acid receptor signaling preserves tendon stem cell characteristics and prevents spontaneous differentiation in vitrox. AB - BACKGROUND: Previous studies have reported that adult mesenchymal stem cells (MSCs) tend to gradually lose their stem cell characteristics in vitro when placed outside their niche environment. They subsequently undergo spontaneous differentiation towards mesenchymal lineages after only a few passages. We observed a similar phenomenon with adult tendon stem cells (TSCs) where expression of key tendon genes such as Scleraxis (Scx), are being repressed with time in culture. We hypothesized that an environment able to restore or maintain Scleraxis expression could be of therapeutic interest for in vitro use and tendon cell-based therapies. METHODS: TSCs were isolated from human cadaveric Achilles tendon and expanded for 4 passages. A high content imaging assay that monitored the induction of Scx protein nuclear localization was used to screen ~1000 known drugs. RESULTS: We identified retinoic acid receptor (RAR) agonists as potent inducers of nuclear Scx in the small molecule screen. The upregulation correlated with improved maintenance of tendon stem cell properties through inhibition of spontaneous differentiation rather than the anticipated induction of tenogenic differentiation. Our results suggest that histone epigenetic modifications by RAR are driving this effect which is not likely only dependent on Scleraxis nuclear binding but also mediated through other key genes involved in stem cell self renewal and differentiation. Furthermore, we demonstrate that the effect of RAR compounds on TSCs is reversible by revealing their multi-lineage differentiation ability upon withdrawal of the compound. CONCLUSION: Based on these findings, RAR agonists could provide a valid approach for maintaining TSC stemness during expansion in vitro, thus improving their regenerative potential for cell-based therapy. PMID- 27001427 TI - Modulation of biosynthesis of photosynthetic pigments and light-harvesting complex in wild-type and gun5 mutant of Arabidopsis thaliana during impaired chloroplast development. AB - Plants in response to different environmental cues need to modulate the expression of nuclear and chloroplast genomes that are in constant communication. To understand the signals that are responsible for inter-organellar communication, levulinic acid (LA), an inhibitor of 5-aminolevulinic acid dehydratase, was used to suppress the synthesis of pyrrole-derived tetrapyrroles chlorophylls. Although, it does not specifically inhibit carotenoid biosynthesis enzymes, LA reduced the carotenoid contents during photomorphogenesis of etiolated Arabidopsis seedlings. The expression of nuclear genes involved in carotenoid biosynthesis, i.e., geranylgeranyl diphosphate synthase, phytoene synthase, and phytoene desaturase, was downregulated in LA-treated seedlings. Similarly, the transcript abundance of nuclear genes, i.e., Lhcb1, PsbO, and RcbS, coding for chloroplastic proteins was severely attenuated in LA-treated samples. In contrast, LA treatment did not affect the transcript abundance of chalcone synthase, a marker gene for cytoplasm, and beta-ATP synthase, a marker gene for mitochondria. This demonstrates the retrograde signaling from chloroplast to nucleus to suppress chloroplastic proteins during impaired chloroplast development. However, under identical conditions in LA-treated tetrapyrrole-deficient gun5 mutant, retrograde signal continued. The tetrapyrrole biosynthesis inhibitor LA suppressed formation of all tetrapyrroles both in WT and gun5. This rules out the role of tetrapyrroles as signaling molecules in WT and gun5. The removal of LA from the Arabidopsis seedlings restored the chlorophyll and carotenoid contents and expression of nuclear genes coding for chloroplastic proteins involved in chloroplast biogenesis. Therefore, LA could be used to modulate chloroplast biogenesis at a desired phase of chloroplast development. PMID- 27001428 TI - Stimulus-dependent synchronization in delayed-coupled neuronal networks. AB - Time delay is a general feature of all interactions. Although the effects of delayed interaction are often neglected when the intrinsic dynamics is much slower than the coupling delay, they can be crucial otherwise. We show that delayed coupled neuronal networks support transitions between synchronous and asynchronous states when the level of input to the network changes. The level of input determines the oscillation period of neurons and hence whether time-delayed connections are synchronizing or desynchronizing. We find that synchronizing connections lead to synchronous dynamics, whereas desynchronizing connections lead to out-of-phase oscillations in network motifs and to frustrated states with asynchronous dynamics in large networks. Since the impact of a neuronal network to downstream neurons increases when spikes are synchronous, networks with delayed connections can serve as gatekeeper layers mediating the firing transfer to other regions. This mechanism can regulate the opening and closing of communicating channels between cortical layers on demand. PMID- 27001430 TI - Successful Treatment of Severe Immune Thrombocytopenia After Orthotopic Liver Transplant. AB - Here, we report a case of severe immune thrombocytopenia that occurred after orthotopic liver transplant. On day 16 after transplant, the patient was readmitted to our hospital with a platelet count of 0 cells/mL, with the count remaining at a low level of 1000 to 10 000 cells/mL for 46 days. A diagnosis was made, after exclusion of other causes, of thrombocytopenia. Platelet blood transfusion and high-dose prednisone (1mg/kg/d) combined with intravenous immunoglobulin (0.5g/kg/d) were administered with no improvement. After additional treatments, which included altered use of immunosuppressive agents, changing adefovir to lamivudine and continuous steroid therapy, the patient was discharged with a platelet count of 55 000 cells/mL. Both liver and renal functions generally stayed well during hospitalization. The patient was discharged uneventfully and achieved remission during 10-month follow-up after discharge. PMID- 27001431 TI - Diagnostic dilemmas in enlarged and diffusely hemorrhagic adrenal glands. AB - We have noted an increasing number of cases of enlarged adrenal glands where the underlying diagnosis was masked by a diffusely hemorrhagic process. We identified from our database 59 cases (32 consults, 27 routine) of adrenal glands with diffuse (>25%) hemorrhage received between 2000 and 2014. Fifty-three adrenalectomies and 6 biopsies were identified. The diagnoses after central review were 41 adrenocortical adenomas, 1 nodular adrenocortical hyperplasia with associated myelolipoma, 1 benign adrenocortical cyst, and 10 nonneoplastic adrenal glands with hemorrhage. A definitive diagnosis for the 6 biopsies was precluded by the sample size. The adrenocortical adenomas (size, 1-13 cm; 25%-95% hemorrhage) showed clear cell change in the neoplastic area (10%-80% of the tumor), 19 showed focal calcification (1 with ossification), 11 showed areas of papillary endothelial hyperplasia, 10 showed scattered lymphoplasmacytic inflammation, 6 showed benign cortical tissue extending beyond the adrenal capsule into soft tissue, 1 showed necrosis in the form of ghost cells, 2 showed lipomatous change, and 6 were associated with incidental benign lesions (1 cortical cyst, 1 schwannoma, and 4 myelolipomas). Twenty-four of the adrenocortical adenomas were consults where the referring pathologist had trouble classifying the lesion. Of the 10 nonneoplastic adrenals (4.5-22 cm; 40%-80% hemorrhage), 2 were consults. In summary, pathologists have difficulties recognizing adrenocortical adenomas in the setting of a massively enlarged and hemorrhagic adrenal gland. Although there is a correlation between adrenocortical malignancy and size, hemorrhage into nonmalignant adrenal glands can result in markedly enlarged adrenals. PMID- 27001432 TI - Medullary carcinoma in the colorectum: a systematic review and meta-analysis. AB - Medullary carcinoma (MC) is a very rare variant of colorectal carcinoma (CRC). Its clinicopathologic findings are not fully elucidated. The aim of this study was to investigate the clinicopathological characteristics of MC in the colorectum through a systematic review and meta-analysis. The meta-analysis examined the incidence, age, sex, site, mismatch repair deficiency (MMRd), MMR protein expression, ARID1A expression, BRAF(V600E) mutation, KRAS mutation, and survival rate of MC. The 21469 CRCs included 462 MCs in 16 eligible studies, representing an estimated incidence of MC of 0.027 (95% confidence interval [CI] 26 0.016-0.045). MC frequently occurred in female patients and in the right colon. Lymph node metastasis of MC was significantly lower than that of poorly differentiated adenocarcinoma/undifferentiated adenocarcinoma (PDA/UDA). In addition, MC had a higher MMRd rate (0.892, 95% CI 0.758-0.956), higher BRAF(V600E) mutation rate (0.652, 95% CI 0.143-0.954) and lower KRAS mutation rate (0.171, 95% CI 0.065-0.378) than PDA/UDA and conventional adenocarcinoma. Patients with MC had significantly better overall survival rate compared to patients with PDA/UDA (hazard ratio 0.441, 95% CI 0.262-0.742). However, there was no significant difference of overall survival rate between MC and conventional adenocarcinoma patients. MC predominantly occurred in females and in the right colon, and had different molecular characteristics and behaviors compared to PDA/UDA and conventional adenocarcinoma. PMID- 27001433 TI - PIK3CA promotes proliferation and motility but is unassociated with lymph node metastasis or prognosis in esophageal squamous cell carcinoma. AB - The PIK3CA mutation has been extensively reported in the setting of cancers; however, the clinicopathological significance of PIK3CA expression has rarely been discussed in esophageal squamous cell carcinoma. In the present study, to confirm the significance of PIK3CA expression in association with metastasis and prognosis, which has been somewhat controversial in esophageal squamous cell carcinoma (ESCC), the relationship between clinicopathological features of ESCC and PIK3CA expression was analyzed using immunohistochemistry with a tissue microarray. Meanwhile, as additional verification and an ethnic control, another independent small cohort of Kazakh ESCC were analyzed by immunohistochemistry. To investigate the pilot role of PIK3CA in ESCC cells, ESCC cell lines ECa109 and EC9706 were transiently transfected with specific siRNA against PIK3CA. The silencing effect was detected by Western blot. Cell proliferation was examined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay; apoptosis and the cell cycles were analyzed by flow cytometry. Furthermore, the migratory and invasive ability were evaluated by wound healing and transwell invasion assay, respectively. Expression of PIK3CA was significantly higher in ESCC than in paired normal controls and was ethnicity independent; no statistically significant difference was observed between PIK3CA expression and sex, age, depth of invasion, tumor differentiation, lymph node metastasis, or prognosis. Proliferation, migration, and invasion were all markedly reduced after knockout of PIK3CA. Moreover, the cell cycle was arrested at the S phase, and the apoptosis rate was significantly increased, suggesting that PIK3CA plays a key role in promoting the proliferation and motility of ESCC cells. PMID- 27001429 TI - The IL-1 cytokine family and its role in inflammation and fibrosis in the lung. AB - The IL-1 cytokine family comprises 11 members (7 ligands with agonist activity, 3 receptor antagonists and 1 anti-inflammatory cytokine) and is recognised as a key mediator of inflammation and fibrosis in multiple tissues including the lung. IL 1 targeted therapies have been successfully employed to treat a range of inflammatory conditions such as rheumatoid arthritis and gouty arthritis. This review will introduce the members of the IL-1 cytokine family, briefly discuss the cellular origins and cellular targets and provide an overview of the role of these molecules in inflammation and fibrosis in the lung. PMID- 27001434 TI - The expression profiles of the galectin gene family in colorectal adenocarcinomas. AB - We aim to investigate the expression profiles of galectin family genes (galectins 1, 2, 3, 4, 7, 8, 9, 10, and 11) in colorectal carcinomas. Messenger RNA (mRNA) expression of galectin family members (1, 2, 3, 4, 7, 8, 9, 10, and 12) was analyzed by real-time polymerase chain reaction in colorectal tissues from 201 patients (54 noncancer colorectal tissues, 49 adenomas, and 98 adenocarcinomas). Galectin-1 and galectin-3 protein expressions were determined by immunohistochemistry. In general, high galectin mRNA expression was noted in colorectal carcinomas in early stages of their pathogenesis. Significant differences in galectins-2, 3, 7, 8, and 10 mRNA expression were associated with pathologic stages (P<.05). Increased prevalence of galectins-2, 7, 8, and 10 mRNA overexpression was noted in nonmetastatic colorectal carcinomas (P<.05). Galectin 1 and galectin-3 proteins were present in the nucleus and cytoplasm of the colorectal tissues and expressed significantly higher in colorectal carcinomas when compared to colorectal adenomas (61% and 95%, respectively). Patients with colorectal carcinoma with high levels of galectin-3 mRNA and protein expression showed better prognosis (P=.052). To conclude, many novel correlations between the deregulation of galectin family genes and various clinicopathological features in colorectal adenocarcinoma were noted. Overexpression of galectins at the mRNA level and proteins were predominant in earlier stages of colorectal carcinomas. These altered expression patterns of galectin genes suggest the multifunctional role of galectin genes in the regulation of colorectal cancer development, progression, and metastasis. PMID- 27001436 TI - Associations between meal and snack frequency and overweight and abdominal obesity in US children and adolescents from National Health and Nutrition Examination Survey (NHANES) 2003-2012. AB - The association between eating frequency (EF) and adiposity in young populations is inconsistent. This cross-sectional study examined associations of EF, meal frequency (MF) and snack frequency (SF) with adiposity measures in US children aged 6-11 years (n 4346) and adolescents aged 12-19 years (n 6338) participating in the National Health and Nutrition Examination Survey 2003-2012. Using data from two 24-h dietary recalls, all eating occasions providing >=210 kJ of energy were divided into meals or snacks based on contribution to energy intake (>=15 or <15 %), self-report and time (06.00-09.00, 12.00-14.00 and 17.00-20.00 hours or others). When analysed without adjustment for the ratio of reported energy intake:estimated energy requirement (EI:EER), all measures of EF, MF and SF showed inverse or null associations with overweight (BMI>=85th percentile of BMI for-age) and abdominal obesity (waist circumference>=90th percentile) in both children and adolescents. After adjustment for EI:EER, however, EF and SF, but not MF, showed positive associations in children, irrespective of the definition of meals and snacks. In adolescents, after adjustment for EI:EER, positive associations were observed for EF (abdominal obesity only), SF based on energy contribution and MF based on self-report, whereas there was an inverse association between MF based on energy contribution and overweight. In conclusion, higher SF and EF, but not MF, were associated with higher risks of overweight and abdominal obesity in children, whereas associations varied in adolescents, depending on the definition of meals and snacks. Prospective studies are needed to establish the associations observed here. PMID- 27001435 TI - Update on parathyroid carcinoma. AB - INTRODUCTION: Parathyroid carcinoma (PC) is a rare endocrine disorder, commonly causing severe primary hyperparathyroidism (PHPT). PC is mainly a sporadic disease, but it may occur in familial PHPT. Patients with PC usually present markedly elevated serum calcium and PTH. The clinical features are mostly due to the effects of the excessive secretion of PTH rather than to the spread of tumor. At times, the diagnosis can be difficult. PURPOSE: The aim of this work is to review the available data on PC, and focus its molecular pathogenesis and the clinical utility of CDC73 genetic testing and immunostaining of its product, parafibromin. The pathological diagnosis of PC is restricted to lesions showing unequivocal growth into adjacent tissues or metastasis. Inactivating mutations of the cell division cycle 73 (CDC73) gene have been identified in up to 70 % of apparently sporadic PC and in one-third are germline. Loss of parafibromin immunostaining has been shown in most PC. The association of CDC73 mutations and loss of parafibromin predicts a worse clinical outcome and a lower overall 5- and 10-year survival. CONCLUSIONS: The treatment of choice is the en bloc resection of the tumor. The course of PC is variable; most patients have local recurrences or distant metastases and die from unmanageable hypercalcemia. PMID- 27001437 TI - Drought and Recovery: Independently Regulated Processes Highlighting the Importance of Protein Turnover Dynamics and Translational Regulation in Medicago truncatula. AB - Climate change in conjunction with population growth necessitates a systems biology approach to characterize plant drought acclimation as well as a more thorough understanding of the molecular mechanisms of stress recovery. Plants are exposed to a continuously changing environment. Extremes such as several weeks of drought are followed by rain. This requires a molecular plasticity of the plant enabling drought acclimation and the necessity of deacclimation processes for recovery and continuous growth.During drought stress and subsequent recovery, the metabolome and proteome are regulated through a sequence of molecular processes including synthesis and degradation and molecular interaction networks are part of this regulatory process. In order to study this complex regulatory network, a comprehensive analysis is presented for the first time, investigating protein turnover and regulatory classes of proteins and metabolites during a stress recovery scenario in the model legume Medicago truncatula The data give novel insights into the molecular capacity and differential processes required for acclimation and deacclimation of severe drought stressed plants.Functional cluster and network analyses unraveled independent regulatory mechanisms for stress and recovery with different dynamic phases that during the course of recovery define the plants deacclimation from stress. The combination of relative abundance levels and turnover analysis revealed an early transition phase that seems key for recovery initiation through water resupply and is independent from renutrition. Thus, a first indication for a metabolite and protein-based load capacity was observed necessary for the recovery from drought, an important but thus far ignored possible feature toward tolerance. The data indicate that apart from the plants molecular stress response mechanisms, plasticity may be related to the nutritional status of the plant prior to stress initiation. A new perspective and possible new targets as well as metabolic mechanisms for future plant-bioengineering toward enhanced drought stress tolerance are presented. PMID- 27001438 TI - Characterization of an in vitro fed-batch model to obtain cells released from S. epidermidis biofilms. AB - Both dynamic and fed-batch systems have been used for the study of biofilms. Dynamic systems, whose hallmark is the presence of continuous flow, have been considered the most appropriate for the study of the last stage of the biofilm lifecycle: biofilm disassembly. However, fed-batch is still the most used system in the biofilm research field. Hence, we have used a fed-batch system to collect cells released from Staphylococcus epidermidis biofilms, one of the most important etiological agents of medical device-associated biofilm infections. Herein, we showed that using this model it was possible to collect cells released from biofilms formed by 12 different S. epidermidis clinical and commensal isolates. In addition, our data indicated that biofilm disassembly occurred by both passive and active mechanisms, although the last occurred to a lesser extent. Moreover, it was observed that S. epidermidis biofilm-released cells presented higher tolerance to vancomycin and tetracycline, as well as a particular gene expression phenotype when compared with either biofilm or planktonic cells. Using this model, biofilm-released cells phenotype and their interaction with the host immune system could be studied in more detail, which could help providing significant insights into the pathophysiology of biofilm related infections. PMID- 27001439 TI - Contrasted enzymatic cocktails reveal the importance of cellulases and hemicellulases activity ratios for the hydrolysis of cellulose in presence of xylans. AB - Various enzymatic cocktails were produced from two Trichoderma reesei strains, a cellulase hyperproducer strain and a strain with beta-glucosidase activity overexpression. By using various carbon sources (lactose, glucose, xylose, hemicellulosic hydrolysate) for strains growth, contrasted enzymatic activities were obtained. The enzymatic cocktails presented various levels of efficiency for the hydrolysis of cellulose Avicel into glucose, in presence of xylans, or not. These latter were also hydrolyzed with different extents according to cocktails. The most efficient cocktails (TR1 and TR3) on Avicel were richer in filter paper activity (FPU) and presented a low ratio FPU/beta-glucosidase activity. Cocktails TR2 and TR5 which were produced on the higher amount of hemicellulosic hydrolysate, possess both high xylanase and beta-xylosidase activities, and were the most efficient for xylans hydrolysis. When hydrolysis of Avicel was conducted in presence of xylans, a decrease of glucose release occurred for all cocktails compared to hydrolysis of Avicel alone. Mixing TR1 and TR5 cocktails with two different ratios of proteins (1/1 and 1/4) resulted in a gain of efficiency for glucose release during hydrolysis of Avicel in presence of xylans compared to TR5 alone. Our results demonstrate the importance of combining hemicellulase and cellulase activities to improve the yields of glucose release from Avicel in presence of xylans. In this context, strategies involving enzymes production with carbon sources comprising mixed C5 and C6 sugars or combining different cocktails produced on C5 or on C6 sugars are of interest for processes developed in the context of lignocellulosic biorefinery. PMID- 27001440 TI - Crystal structure and molecular mechanism of an aspartate/glutamate racemase from Escherichia coli O157. AB - EcL-DER, the aspartate/glutamate racemase from the pathogen Escherichia coli O157, exhibits racemase activity for l-aspartate and l-glutamate. This study reports the crystal structures of apo-EcL-DER, the EcL-DER-l-aspartate and the EcL-DER-d-aspartate complexes. The EcL-DER structure contains two domains, forming pseudo-mirror symmetry in the active site. A unique catalytic pair consisting of Thr(83) and Cys(197) exists in the active site. The characteristic conformations of l-Asp and d-Asp in the active site provide a straight structural evidence for the racemization mechanism of EcL-DER. In addition, the diversity of catalytic pairs implies that PLP-independent amino acid racemases adopt various catalytic mechanisms and are classified into different subgroups. PMID- 27001441 TI - Influence of self-care advice on patient satisfaction and healthcare utilization. AB - AIM: The aim of this study is to explore the influence of nurse-led self-care advice on healthcare utilization and patients' satisfaction with telephone nursing. BACKGROUND: Many consultations in high-cost settings are for conditions that are manageable through self-care and callers with greater satisfaction with the nurse interaction are nearly four times more likely to engage in self-care. DESIGN: Cross-sectional study. METHODS: Questionnaires were sent out to 500 randomly selected callers to the Swedish Healthcare Direct in Northern Sweden during March 2014. Callers were asked about their satisfaction with the consultation, their intended actions prior to consultation, the recommendation given by the nurse and the action undertaken after the call. RESULTS: Young callers and persons recommended watchful waiting or recurrence if no improvements were significantly less satisfied with their care. When calling on their own behalf, both men and women rated the severity of their symptoms equally and were advised to self-care to the same extent. Self-care advice had a constricting influence on self-reported healthcare utilization, with 66.1% of cases resulting in a lower level of care than first intended. Feeling reassured after the call was the aspect of nursing care that influenced satisfaction the most. CONCLUSION: Receiving self-care advice rather than referral to a general practitioner influences patient satisfaction negatively. Feeling reassured after consultation is strongly related to satisfaction, which in turn has been found to increase the likelihood of engaging in self-care behaviour. PMID- 27001442 TI - Worldwide trends in surgical techniques in the treatment of esophageal and gastroesophageal junction cancer. AB - The aim of this study was to evaluate the worldwide trends in surgical techniques for esophageal cancer surgery by comparing it to our survey from 2007. In addition, new questions were added for gastroesophageal junction (GEJ) cancer. An international survey on surgery of esophageal and GEJ cancer was performed among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association. Also, surgeons from personal networks were contacted. The participants filled out a web based questionnaire about surgical strategies for esophageal and gastroesophageal cancer. The overall response rate was 478/1147 (42%). The respondents represented 49 different countries and 6 different continents. The annual cumulative number of esophageal and gastric resections per surgeon was low (<=11) in 11%, medium (11-21) in 17%, and high (>=21) in 72% of respondents. In a subgroup analysis of esophageal surgeons the number of high volume surgeons increased from 45 to 54% over the past 7 years. The preferred lymph node dissection was two-field in 86%. A gastric conduit was the preferred method of reconstruction in 95%. In 2014, the preferred approach to esophagectomy was minimally invasive transthoracic in 43%, compared with 14% in 2007. In minimally invasive transthoracic esophagectomy the cervical anastomosis was favored in 54% of respondents in 2014 compared with 87% in 2007. The preferred technique of construction of the cervical anastomosis was hand-sewn in 64% and stapled in 36%, whereas the thoracic anastomosis was stapled in 77% and hand-sewn in 23%. The preferred surgical approach for Siewert type 1 tumors (5-1 cm proximal of the GEJ) was esophagectomy in 93% of respondents, whereas 6% favored gastrectomy and 3% combined a distal esophagectomy with a proximal gastrectomy. For Siewert type 2 tumors (1-2 cm from the GEJ) an extended gastrectomy was favored by 66% of respondents, followed by esophagectomy in 27% and total gastrectomy in 7%. Siewert type 3 tumors (2-5 cm distal of the GEJ) were preferably treated with gastrectomy in 90% of respondents, esophagectomy in 6%, and extended gastrectomy in 4%. The preferred curative surgical treatment of esophageal cancer is minimally invasive transthoracic esophagectomy with a two field lymph node dissection and gastric conduit reconstruction. A strong worldwide trend toward minimally invasive surgery is observed. The preferred surgical treatment of GEJ tumors is esophagectomy for Siewert type 1 tumors and gastrectomy for Siewert type 3 tumors. The majority of surgeons favor an extended gastrectomy for Siewert type 2 tumors. PMID- 27001443 TI - The treatment of canine mast cell tumours with electrochemotherapy with or without surgical excision. AB - To describe the results of electrochemotherapy (ECT) in dogs with mast cell tumours (MCTs) either as first line therapy or as an adjuvant to surgery. The treatment combines administration of low dose chemotherapeutic drugs with the application of microsecond electric pulses, which cause the temporary permeabilization and increased porosity of the tumour cell membranes. The design of this study is a retrospective case series. A total of 51 dogs with MCTs were included and classified according to ECT procedure into 4 groups (ECT only, 15 cases, intra-surgery ECT, 11, ECT Adjuvant to surgery, 14, Surgery followed by ECT, 11). The four groups (staged with location, size and grade) were evaluated to assess complete or partial remission, disease free interval, overall survival time and local toxicity. In this case series, Boxers, mixed breed and Labrador Retrievers, male dogs, between 4 and 9 years old were more represented. MCTs were predominantly grade 2 (Patnaik) and T stage 0-1, I-1 (World Health Organization). Treated lesions were most commonly identified on the hindlimb and head where curative surgery would involve cosmetic or functional compromise. The intra surgery group of dogs showed the best disease free interval with Kaplan-Meyer analysis. Local toxicity induced by ECT ranged mostly from 1 to 4 in a 5-point arbitrary scale with 0 - no toxicity to 5 - highest toxicity. In this study, ECT can be applied successfully as an exclusive therapy in smaller MCTs as an alternative to surgery. ECT can be combined with surgery either intra-operatively or post operatively for larger lesions without significant toxicity. PMID- 27001444 TI - First Clinical Experience with ONO-4232: A Randomized, Double-blind, Placebo controlled Healthy Volunteer Study of a Novel Lusitropic Agent for Acutely Decompensated Heart Failure. AB - PURPOSE: The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic parameters of up to 15 dose levels of ONO-4232, a selective agonist for the EP4 subtype of the prostaglandin E2 receptor, with a dual left ventricular lusitropic and venodilatory action, in healthy, adult, male and female volunteers. METHODS: In this randomized, single-center, double-blind, placebo-controlled, single-dose, sequential-group escalation, first in human study, ONO-4232 (0.001, 0.003, 0.01, 0.02, 0.04, 0.08, 0.12, 0.15, 0.18, or 0.27 ng/kg/min) or placebo was administered as a continuous intravenous infusion over 3 hours. Safety, tolerability, and pharmacokinetic data were collected during dosing and over a period of 3 days (Day -1 to Day 2), and at the follow-up visit (Day 7 [+/-2 days]). FINDINGS: Fifty-seven subjects received ONO-4232 and 19 subjects received placebo. Ten of the planned 15 cohorts (dose range, 0.001-0.27 ng/kg/min) were conducted. A total of 34 treatment-emergent adverse events (TEAEs) were reported in 23 subjects. Overall, the majority of TEAEs were mild. No serious TEAEs or deaths were reported and no subjects discontinued due to adverse events. The most frequently reported TEAE was infusion site erythema. A decrease in systolic blood pressure from baseline occurred for ONO-4232 subjects compared with placebo that was statistically significant for the 0.08 ng/kg/min dose, and a dose-dependent increase in heart rate starting at 0.04 ng/kg/min and achieving statistical significance compared with placebo at 0.15 ng/kg/min and above. More orthostatic events occurred in the higher-dose groups and the dose escalation was terminated due to increasing occurrences of orthostatic hypotension/intolerance. Plasma concentrations of ONO-4232 reached steady state approximately 2 hours after the start of infusion and then declined rapidly after the end of infusion, and systemic exposure appeared to increase in a dose proportional manner. Approximately 30% of the administered dose of ONO-4232 was excreted in the urine. IMPLICATIONS: In healthy adults ONO-4232 was generally well tolerated in the dose range of 0.001 to 0.27 ng/kg/min. There were dose related changes in systolic blood pressure and heart rate. Infusion site erythema, which was likely associated with a venodilatory effect and possible evidence for the pharmacologic effects of ONO-4232, occurred increasingly with increasing dose. Pharmacokinetic parameters appeared to be dose-proportional. The study results support further evaluation of the cardiovascular effects of this first-in-class selective left ventricular lusitropic and venodilatory drug in patients with acutely decompensated heart failure. PMID- 27001445 TI - From Bottles to Diapers: How Manipulating and Exploring the Microbiome Is Defining Newborn Care. PMID- 27001446 TI - Multiscale computational modeling of (13)C DNP in liquids. AB - Dynamic nuclear polarization (DNP) enables the substantial enhancement of the NMR signal intensity in liquids. While proton DNP is dominated by the dipolar interaction between the electron and nuclear spins, the Fermi contact (scalar) interaction is equally important for heavier nuclei. The impossibility to predict the magnitude and field dependence of the scalar contribution hampers the application of high-field DNP to nuclei other than (1)H. We demonstrate that molecular dynamics (MD) simulations followed by density functional calculations of the Fermi contacts along the MD trajectory lead to quantitative agreement with the DNP coupling factors of the methyl and carbonyl carbons of acetone in water at 0.35 T. Thus, the accurate calculation of scalar-dominated DNP enhancement at a desired magnetic field is demonstrated for the first time. For liquid chloroform at fields above 9 T, our methodology predicts direct (13)C DNP enhancements that are two orders of magnitude larger than those of (1)H. PMID- 27001447 TI - Trends in P2Y12 Inhibitor Use in Patients Referred for Invasive Evaluation of Coronary Artery Disease in Contemporary US Practice. AB - Practice in patients undergoing invasive evaluation for coronary artery disease is variable regarding choice of P2Y12 inhibitor and timing of treatment initiation and is usually dictated by institutional or even individual operator preference. Limited data are available on the actual patterns of P2Y12 inhibitor use in contemporary practice in the United States. We used electronic medical records from the Cerner "Health Facts" database of adults who underwent coronary angiography with or without percutaneous coronary intervention (PCI) from January 2008 to June 2013 and who received a loading dose of clopidogrel, prasugrel, or ticagrelor at any time from 48 hours before the start of procedure up to 6 hours after. Timing of P2Y12 inhibitor administration was categorized as >2 hours before, 0 to 2 hours before (pretreatment groups), or after the start of procedure. Results were also evaluated according to type of P2Y12 inhibitor and patient clinical presentation. A total of 37,964 patients underwent coronary angiography, and 28,306 proceeded to PCI. Pretreatment with a P2Y12 inhibitor was observed in 28% and 23% in the overall and PCI populations, respectively. Moderate variability of pretreatment rates was noted relative to clinical presentation and P2Y12 inhibitor type. Pretreatment rates remained fairly constant over time with the exception of a decreasing trend with prasugrel. In conclusion, among patients referred for invasive evaluation of coronary artery disease, P2Y12 inhibitor pretreatment was low in contemporary US practice, an observation consistent over time and for all available agents and clinical presentations. PMID- 27001448 TI - Usefulness of the CHA2DS2-VASC Score to Predict Adverse Outcomes in Patients Having Percutaneous Coronary Intervention. AB - The application of the CHA2DS2-VASC score as a novel risk stratification tool for predicting outcome in clinical applications other than atrial fibrillation and stroke prevention has been previously examined. However, its usefulness in a population of patients with coronary artery disease after percutaneous coronary intervention (PCI) has not been explored. We investigated 12,785 consecutive patients who underwent PCI in a tertiary medical center from April 2004 to August 2014 (mean follow-up 6.5 years) and computed the CHA2DS2-VASC score on their index PCI. We assessed the relation between the CHA2DS2-VASC score and clinical outcomes (for example, all-cause mortality and mortality or myocardial infarction) at 1 and 5 years. The mean CHA2DS2-VASC score was 3.7 +/- 1.7, 59.1% of patients obtained a score of 3 to 5. Both the primary and secondary outcomes at 1 and 5 years were significantly more frequent as the CHA2DS2-VASC score increased. Overall, the mortality rate after PCI was 10 times higher for patients with a CHA2DS2-VASC score of 5 compared with a score of 1 at both 1-and 5-year follow-up. The CHA2DS2-VASC score predicted all-cause mortality and death or nonfatal myocardial infarction in a significant (p <0.001, C-index 0.73 and 0.72) and linear fashion. In conclusion, the CHA2DS2-VASC score can be used as a simple and effective tool to predict long-term clinical outcomes in patients undergoing PCI. PMID- 27001449 TI - Impact of Race, Ethnicity, and Multimodality Biomarkers on the Incidence of New Onset Heart Failure With Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis). AB - Heart failure with preserved ejection fraction (HFpEF) is a prevalent condition with no established prevention or treatment strategies. Furthermore, the pathophysiology and predisposing risk factors for HFpEF are incompletely understood. Therefore, we sought to characterize the incidence and determinants of HFpEF in the Multi-Ethnic Study of Atherosclerosis (MESA). Our study included 6,781 MESA participants (White, Black, Chinese, and Hispanic men and women age 45 to 84 years, free of baseline cardiovascular disease). The primary end point was time to diagnosis of HFpEF (left ventricular ejection fraction >=45%). Multivariable adjusted hazard ratios (HRs) with 95% confidence intervals were calculated to identify predictors of HFpEF. Over median follow-up of 11.2 years (10.6 to 11.7), 111 subjects developed HFpEF (cumulative incidence 1.7%). Incidence rates were similar across all races/ethnicities. Age (HR 2.3 [1.7 to 3.0]), hypertension (HR 1.8 [1.1 to 2.9]), diabetes (HR 2.3 [1.5 to 3.7]), body mass index (HR 1.4 [1.1 to 1.7]), left ventricular hypertrophy by electrocardiography (HR 4.3 [1.7 to 11.0]), interim myocardial infarction (HR 4.8 [2.7 to 8.6]), elevated N-terminal of the prohormone brain natriuretic peptide (HR 2.4 [1.5 to 4.0]), detectable troponin T (HR 4.5 [1.9 to 10.9]), and left ventricular mass index by magnetic resonance imaging (MRI; 1.3 [1.0 to 1.6]) were significant predictors of incident HFpEF. Worsening renal function, inflammatory markers, and coronary artery calcium were significant univariate but not multivariate predictors of HFpEF. Gender was neither a univariate nor multivariate predictor of HFpEF. In conclusion, we demonstrate several risk factors and biomarkers associated with incident HFpEF that were consistent across different racial/ethnic groups and may represent potential therapeutic targets for the prevention and treatment of HFpEF. PMID- 27001451 TI - Omnidirectional optical attractor in structured gap-surface plasmon waveguide. AB - An optical attractor based on a simple and easy to fabricate structured metal dielectric-metal (SMDM) waveguide is proposed. The structured waveguide has a variable thickness in the vicinity of an embedded microsphere and allow for adiabatic nano-focusing of gap-surface plasmon polaritons (GSPPs). We show that the proposed system acts as an omnidirectional absorber across a broad spectral range. The geometrical optics approximation is used to provide a description of the ray trajectories in the system and identify the singularity of the deflection angle at the photon sphere. The analytical theory is validated by full-wave numerical simulations demonstrating adiabatic, deep sub-wavelength focusing of GSPPs and high local field enhancement. The proposed structured waveguide is an ideal candidate for the demonstration of reflection free omnidirectional absorption of GSPP in the optical and infrared frequency ranges. PMID- 27001450 TI - Investigating direct interaction between Escherichia coli topoisomerase I and RecA. AB - Protein-protein interactions are of special importance in cellular processes, including replication, transcription, recombination, and repair. Escherichia coli topoisomerase I (EcTOP1) is primarily involved in the relaxation of negative DNA supercoiling. E. coli RecA, the key protein for homologous recombination and SOS DNA-damage response, has been shown to stimulate the relaxation activity of EcTOP1. The evidence for their direct protein-protein interaction has not been previously established. We report here the direct physical interaction between E. coli RecA and topoisomerase I. We demonstrated the RecA-topoisomerase I interaction via pull-down assays, and surface plasmon resonance measurements. Molecular docking supports the observation that the interaction involves the topoisomerase I N-terminal domains that form the active site. Our results from pull-down assays showed that ATP, although not required, enhances the RecA-EcTOP1 interaction. We propose that E. coli RecA physically interacts with topoisomerase I to modulate the chromosomal DNA supercoiling. PMID- 27001452 TI - Coordination Chemistry Inside Polymeric Nanoreactors: Interparticle Metal Exchange and Ionic Compound Vectorization in Phosphine-Functionalized Amphiphilic Polymer Latexes. AB - Stable latexes of hierarchically organized core-cross-linked polymer micelles that are functionalized at the core with triphenylphosphine (TPP@CCM) have been investigated by NMR spectroscopic analysis at both natural (ca. pH 5) and strongly basic (pH 13.6) pH values after core swelling with toluene. The core shell interface structuring forces part of the hydrophilic poly(ethylene oxide) (PEO) chains to reside inside the hydrophobic core at both pH values. Loading the particle cores with [Rh(acac)(CO)2 ] (acac=acetylacetonate) at various Rh/P ratios yielded polymer-supported [Rh(acac)(CO)(TPP)] (TPP=triphenylphosphine). The particle-to-particle rhodium migration is very fast at natural pH, but slows down dramatically at high pH, whereas the size distribution of the nanoreactors remains unchanged. The slow migration at pH 13.6 leads to the generation of polymer-anchored [Rh(OH)(CO)(TPP)2 ], which is also generated immediately upon the addition of NaOH to the particles with a [Rh(acac)(CO)] loading of 50 %. Similarly, treatment of the same particles with NaCl yielded polymer-anchored [RhCl(CO)(TPP)2 ]. Interparticle coupling occurs during these rapid processes. These experiments prove that the major contribution to metal migration is direct core-core contact. The slow migration at the high pH value, however, must result from a pathway that does not involve core-core contact. The facile penetration of the polymer cores by NaOH and NaCl results from the presence of shell-linked poly(ethylene oxide) methyl ether functions both outside and inside the polymer core-shell interface. PMID- 27001453 TI - Task-positive and task-negative networks and their relation to depression: EEG beamformer analysis. AB - Major Depressive Disorder (MDD) has been associated with predominance of the default-mode network (DMN) over the task-positive network (TPN), which is considered a neurobiological base for ruminative responding. It is not known whether this predominance is a signature of the full-blown MDD or it already exists at preclinical stages. Besides, all relevant evidence has been obtained using fMRI, which allows for a precise spatial characterization of resting state networks (RSNs), but their neural correlates remain elusive. Here we show that after leakage correction of beamformer-projected resting EEG time series, seed based oscillatory-power envelope correlation analysis allows revealing RSNs with significant similarity to respective fMRI RSNs. In a non-clinical sample, depressive symptoms, as measured by the Beck Depression Inventory, are associated with predominance of DMN over TPN connectivity in the right insula and the right temporal lobe in the delta frequency band. These findings imply that in individuals with heightened level of depressive symptoms, emotional circuits are stronger connected with DMN than TPN and should be more easily engaged in self referential rumination than in responding to environmental challenges. The study's findings are in agreement with fMRI evidence, thus confirming the neural base of the observed in fMRI research effects and showing that implicated in depression neural mechanism may already be in action even at preclinical stages. PMID- 27001454 TI - Familiar companions diminish cocaine conditioning and attenuate cocaine stimulated dopamine release in the nucleus accumbens. AB - This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. PMID- 27001455 TI - Procedural learning as a measure of functional impairment in a mouse model of ischemic stroke. AB - Basal ganglia stroke is often associated with functional deficits in patients, including difficulties to learn and execute new motor skills (procedural learning). To measure procedural learning in a murine model of stroke (30min right MCAO), we submitted C57Bl/6J mice to various sensorimotor tests, then to an operant procedure (Serial Order Learning) specifically assessing the ability to learn a simple motor sequence. Results showed that MCAO affected the performance in some of the sensorimotor tests (accelerated rotating rod and amphetamine rotation test) and the way animals learned a motor sequence. The later finding seems to be caused by difficulties regarding the chunking of operant actions into a coherent motor sequence; the appeal for food rewards and ability to press levers appeared unaffected by MCAO. We conclude that assessment of motor learning in rodent models of stroke might improve the translational value of such models. PMID- 27001456 TI - Altered expression of ATP-sensitive K(+) channels in Hirschsprung's disease. AB - PURPOSE: Hirschsprung's disease-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's disease (HSCR). Altered intestinal epithelial barrier function has been suggested to play a role in the causation of HAEC. In rodent experimental models of colitis, a decreased expression of K(ATP) channels (Subunits: Kir6.1/6.2 and SUR1/2) is reported. We designed this study to determine if K(ATP) channels exist within the human colon and to investigate the expression of different subunits in Hirschsprung's disease. METHODS: We investigated Kir6.1, Kir6.2, SUR1, and SUR2 expression in ganglionic and aganglionic bowel of HD patients (n=5) and controls (n=5). Western blotting and confocal immunofluorescence were performed. MAIN RESULTS: Western blot analysis revealed that Kir6.1, Kir6.2, SUR1, and SUR2 are strongly expressed in the normal human colon. Kir6.1, Kir6.2, SUR1, and SUR2 expression was significantly decreased in the aganglionic bowel compared to ganglionic bowel and controls. Kir6.1 and SUR1 expression were also significantly decreased in the ganglionic bowel of HSCR patients compared to controls. CONCLUSION: We demonstrate for the first time the existence of K(ATP) channels in the human colon. The decreased K(ATP) channel expression in HSCR specimens suggests that an altered K(ATP) expression may interfere with intestinal epithelium barrier function and predispose to HAEC. PMID- 27001457 TI - Removal of foreign bodies from the respiratory tract of young children: Treatment outcomes using newly developed foreign-body grasping forceps. AB - BACKGROUND: Although a foreign body in the airway of children constitutes a medical emergency, most available therapeutic tools are insufficient, and treatment can be difficult. Herein, we evaluated the outcomes of various treatment methods of foreign body removal from the respiratory tract. METHODS: We retrospectively analyzed 24 children (13 boys, 11 girls; median age, 18months [range, 9-60months]) treated for airway foreign bodies from January 1994 to December 2013 by examining their preoperative diagnoses and anesthesia and surgical methods. RESULTS: The foreign body was a peanut, green soybean, almond, chestnut, dental prosthesis, and bead in 15, 3, 3, 1, 1, and 1 cases, respectively. General anesthesia was used in all cases, and flexible bronchoscopy was performed under airway maintenance using a laryngeal mask in 23 cases. The mean operation time was 51+/-32min. Grasping forceps, basket forceps, and a Fogarty catheter were used in 14, 7, and 2 cases, respectively. In July 2003, 3 pronged foreign-body grasping forceps with a 2.0-mm diameter designed for use with a thin bronchoscope were introduced. Of 16 treated cases, 9 were successfully treated with only forceps. The mean operation time was significantly shortened to 38+/-24min (range, 7-91min) compared to the traditional operation time of 82+/-42min (range, 23-147min) (p=0.01). CONCLUSIONS: These novel forceps are useful for reducing the operation time and are suitable for removing airway foreign bodies from children with a narrow tracheobronchial caliber. PMID- 27001458 TI - Analysis of risk factors contributing to morbidity from gastrojejunostomy feeding tubes in children. AB - PURPOSE: The purpose of this study was to define morbidity from gastrojejunostomy tube (GJT) placement in children. METHODS: A retrospective single-center 5-year review of GJT placement in children was performed. Age, weight, prior surgery, indication, type of GJT, and complications (GJT replacement, wound complications, and perforation) were recorded. Logistic regression for morbidity was performed. RESULTS: 142 children underwent 394 GJT placements at a median age of 2.7years (range 5 weeks-18years). The most common indications were failure to thrive (62%) and reflux (25%). Among the 296 GJT replacements, the most common reason was tube dislodgement (30%). Risk factors for replacement, which occurred at a median interval of 12 weeks (range 2days-2.4years), were peristomal complaint (OR=5.4, p=0.02) and prior GJT replacement (OR=1.8, p=0.03). In all, 7 (5%) jejunal perforations occurred at a median of 3 days (range 0-21 days) from GJT placement. Patients with perforation had a median weight of 4.6kg (range 3-11.2kg) and age of 3.9months (range 8 weeks-2.1years). Lower weight (p<0.01) and younger age (p=0.02) predicted perforation, with those weighing less than 6kg (OR=51.9, p<0.001) or younger than 6months (OR=28.6, p<0.01) at highest risk. CONCLUSIONS: GJT placement has a significant risk of recurrent dislodgement and the highest risk of perforation in children weighing less than 6kg or younger than 6months. Alternate feeding options should be strongly considered in this vulnerable population. PMID- 27001460 TI - Paper-based upconversion fluorescence resonance energy transfer biosensor for sensitive detection of multiple cancer biomarkers. AB - A paper-based upconversion fluorescence resonance energy transfer assay device is proposed for sensitive detection of CEA. The device is fabricated on a normal filter paper with simple nano-printing method. Upconversion nanoparticles tagged with specific antibodies are printed to the test zones on the test paper, followed by the introduction of assay antigen. Upconversion fluorescence measurements are directly conducted on the test zones after the antigen-to antibody reactions. Furthermore, a multi-channel test paper for simultaneous detection of multiple cancer biomarkers was established by the same method and obtained positive results. The device showed high anti-interfere, stability, reproducible and low detection limit (0.89 ng/mL), moreover it is very easy to fabricate and operate, which is a promising prospect for a clinical point-of-care test. PMID- 27001461 TI - Mediation analysis of relationships between chronic inflammation and quality of life in older adults. AB - BACKGROUND: This article summarizes exploratory analyses of relationships between chronic inflammation, its physical consequences, and quality of life (QoL). It summarizes key findings from preliminary analyses, and contextualizes these results with extant sociomedical literature to recommend directions for future research. METHODS: Cross-sectional data from the National Social Life, Health, and Aging Project (NSHAP) were used to explore these relationships. Inflammation was assessed via the biomarker C-reactive protein (CRP). We examined associations between CRP levels and two different domains of QoL: happiness with life in general and happiness with intimate relationships. We used ordinal logistic regression with companion OLS models and Sobel-Goodman tests to assess potential mediation, and also conducted a variety of sensitivity analyses. RESULTS: Findings suggest that mediation pathways for the overall association between chronic inflammation and QoL may differ markedly across particular outcome constructs. Specifically, it shows mediation potential for the clinical sequelae of chronic inflammation in frameworks using happiness as an outcome measure, but not in those using relationship satisfaction. Disability appears to mediate the effect of inflammation by 27 %; chronic pain appears to exert a similar mediation effect of 21 %. CONCLUSIONS: Pain and disability linked to chronic inflammation appear to play a small but significant mediating role in the overall reduction in QoL observed among older adults with biomarker evidence of chronic inflammation. We note that these patterns are best framed as dynamic elements of a complex causal fabric, rather than powerful determinants that override other factors contributing to QoL. Hypotheses for further exploration using longitudinal data from the NSHAP are thus offered, pending availability of Wave III data in future years. PMID- 27001462 TI - Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury. AB - Ischemia is the most frequent cause of acute kidney injury (AKI), which is characterized by apoptosis of renal tubular cell. A common result of ischemia in AKI is dysfunction of endoplasmic reticulum (ER), which causes the protein folding capacity to lag behind the protein-folding load. The abundance of misfolded proteins stressed the ER and results in induction of the unfolded protein response (UPR). While the UPR is an adaptive response, over time it can result in apoptosis when cells are unable to recover quickly. Recent research suggests that ER stress is a major factor in renal tubular cell apoptosis resulting from ischemic AKI. Thus, ER stress may be an important new progression factor in the pathology of ischemic AKI. In this article, we review UPR signaling, describe pathology and pathophysiology mechanisms of ischemic AKI, and highlight the dual function of ER stress on renal tubular cell apoptosis. PMID- 27001459 TI - Structure, Regulation and Function of Gap Junctions in Liver. AB - Gap junctions are a specialized group of cell-to-cell junctions that mediate direct intercellular communication between cells. They arise from the interaction of two hemichannels of adjacent cells, which in turn are composed of six connexin proteins. In liver, gap junctions are predominantly found in hepatocytes and play critical roles in virtually all phases of the hepatic life cycle, including cell growth, differentiation, liver-specific functionality and cell death. Liver gap junctions are directed through a broad variety of mechanisms ranging from epigenetic control of connexin expression to post-translational regulation of gap junction activity. This paper reviews established and novel aspects regarding the architecture, control and functional relevance of liver gap junctions. PMID- 27001463 TI - Pu-erh Tea Extract Attenuates Nicotine-Induced Foam Cell Formation in Primary Cultured Monocytes: An in Vitro Mechanistic Study. AB - In this study, the mechanisms by which pu-erh tea extract (PETE) attenuates nicotine-induced foam cell formation were investigated. Monocytes were purified from healthy individuals using commercial antibodies coated with magnetic beads. We found that the nicotine-induced (1-10 MUM) expression of oxidized low-density lipoprotein receptors (ox-LDLRs) and alpha9-nAchRs in monocytes was significantly attenuated by 24 h of PETE (10 MUg/mL; *, p < 0.05) cotreatment. Nicotine (1 MUM for 24 h) significantly induced the expression of the surface adhesion molecule ICAM-1 and the monocyte integrin adhesion molecule (CD11b) by human umbilical vein endothelial cells (HUVECs) and triggered monocytes to differentiate into macrophages via interactions with the endothelium. After treatment with nicotine (0.1-10 MUM for 24 h), the HUVECs released chemotactic factors (IL-8) to attract monocytes into the tunica intima of the artery, and the monocytes then transformed into foam cells. We demonstrated that PETE treatment (>1 MUg/mL for 24 h; *, p < 0.05) significantly attenuates nicotine-induced (1 MUM) monocyte migration toward HUVECs and foam cell formation. This study suggests that tea components effectively attenuate the initial step (foam cell formation) of nicotine-induced atherosclerosis in circulating monocytes. PMID- 27001464 TI - Molecularly Responsive Binding through Co-occupation of Binding Space: A Lock-Key Story. AB - When two guest molecules co-occupy a binding pocket of a water-soluble host, the first guest could be used as a signal molecule to turn on the binding of the second. This type of molecularly responsive binding strongly depends on the size of the two guests and the location of the signal molecule. PMID- 27001465 TI - CK2 inhibition induced PDK4-AMPK axis regulates metabolic adaptation and survival responses in glioma. AB - Understanding mechanisms that link aberrant metabolic adaptation and pro-survival responses in glioma cells is crucial towards the development of new anti-glioma therapies. As we have previously reported that CK2 is associated with glioma cell survival, we evaluated its involvement in the regulation of glucose metabolism. Inhibition of CK2 increased the expression of metabolic regulators, PDK4 and AMPK along with the key cellular energy sensor CREB. This increase was concomitant with altered metabolic profile as characterized by decreased glucose uptake in a PDK4 and AMPK dependent manner. Increased PDK4 expression was CREB dependent, as exogenous inhibition of CREB functions abrogated CK2 inhibitor mediated increase in PDK4 expression. Interestingly, PDK4 regulated AMPK phosphorylation which in turn affected cell viability in CK2 inhibitor treated glioma cells. CK2 inhibitor 4,5,6,7-Tetrabromobenzotriazole (TBB) significantly retarded the growth of glioma xenografts in athymic nude mouse model. Coherent with the in vitro findings, elevated senescence, pAMPK and PDK4 levels were also observed in TBB-treated xenograft tissue. Taken together, CK2 inhibition in glioma cells drives the PDK4 AMPK axis to affect metabolic profile that has a strong bearing on their survival. PMID- 27001466 TI - Enhanced expression of hepatocyte-specific microRNAs in valproic acid mediated hepatic trans-differentiation of human umbilical cord derived mesenchymal stem cells. AB - MicroRNAs (miRNAs) play an important role in the control of cell fate determination during differentiation. In this study, we analyzed the expression pattern of microRNAs (miRNAs) during hepatic trans-differentiation. The protocol employed the use of histone deacetylase inhibitor (HDACI), valproic acid (VPA) to induce hepatic trans-differentiation of human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUC-MSCs). The differentiated hepatocyte like cells (HLCs) from hUC-MSCs shared typical characteristics with mature hepatocytes, including morphology, expression of hepatocyte -specific genes at the molecular and cellular level. Moreover, the functionality of HLCs was confirmed through various liver function tests such as periodic acid-Schiff (PAS) stain for glycogen accumulation, enzyme-linked immunosorbent assay (ELISA) for synthesis of albumin and release of urea. The aim of the present work was to examine the effect of VPA treatment on miRNA expression during hepatic trans differentiation. The analysis at miRNA level showed that there was a significant increase in expression of miRNAs involved in hepatic differentiation, due to VPA pre-treatment during differentiation. The study, thus demonstrated that improved expression of hepatocyte-specific miRNAs, miR-23b cluster (miR-27b-3p, miR-24-1 5p and miR-23b-3p), miR-30a-5p, miR-26a-5p, miR-148a-3p, miR-192-5p, miR-122-5p due to VPA pre-treatment contributed to a more efficient hepatic trans differentiation from hUC-MSCs. The putative targets of these upregulated miRNAs were predicted using Bioinformatics analysis. Finally, miR-122-5p, highly upregulated miRNA during hepatic differentiation, was selected for target verification studies. Thus, this study also provides the basis for the function of miR-122-5p during hepatic differentiation of hUC-MSCs. PMID- 27001467 TI - First report of Cryptosporidium canis in foxes (Vulpes vulpes) and raccoon dogs (Nyctereutes procyonoides) and identification of several novel subtype families for Cryptosporidium mink genotype in minks (Mustela vison) in China. AB - Despite the rapid and extensive advances in molecular epidemiology of Cryptosporidium in humans and a variety of animals, the prevalence and genetic traits of the parasite in wildlife bred in captivity and the role of the neglected hosts in zoonotic transmission of human cryptosporidiosis are rarely understood. This study investigated the prevalence, species/genotype, and subtype of Cryptosporidium in farmed fur animals in China and assessed the possibility of zoonotic transmission. Three of 191 (1.6%) foxes (Vulpes vulpes), 17 of 162 (10.5%) raccoon dogs (Nyctereutes procyonoides), and 48 of 162 (29.6%) minks (Mustela vison) were positive for Cryptosporidium by nested PCRs targeting the small subunit rRNA gene. Sequence analysis indicated the presence of only Cryptosporidium canis in foxes and raccoon dogs. There is no significant difference in prevalence between young and adult foxes (or raccoon dogs). Three Cryptosporidium species or genotype including C. canis, Cryptosporidium meleagridis, and mink genotype were determined in minks aged five to six months. Subtyping based on nucleotide and amino acid sequence polymorphisms of the 60kDa glycoprotein facilitated identification of three novel subtype families named as Xb to Xd for Cryptosporidium mink genotype. The presence of zoonotic C. canis, C. meleagridis, and Cryptosporidium mink genotype in captive-bred fur animals is of public health concerns. The findings expanded the host ranges of C. canis and C. meleagridis and confirmed genetic diversity at the subtype level in Cryptosporidium mink genotype. This is the first study reporting Cryptosporidium infections in foxes and raccoon dogs in China. PMID- 27001468 TI - Assessment of colorimetric amplification methods in a paper-based immunoassay for diagnosis of malaria. AB - Colorimetric detection methods that produce results readable by eye are important for diagnostic tests in resource-limited settings. In this work, we have compared three main types of colorimetric methods - enzymatic reactions, silver deposition catalyzed by gold nanoparticles, and polymerization-based amplification - in a paper-based immunoassay for detection of Plasmodium falciparum histidine-rich protein 2, a biomarker of malarial infection. We kept the binding events in the immunoassay constant in order to isolate the effect of the detection method on the outcome of the test. We have highlighted that the optimal readout time in a test can vary significantly - ranging from immediately after addition of a visualization agent to 25 minutes after addition of a visualization agent - depending on the colorimetric method being used, and accurate time keeping is essential to prevent false positives in methods where substantial color develops over time in negative tests. We have also shown that the choice of a colorimetric method impacts the calculated limit-of-detection, the ease of visual perception of the readout, and the total cost of the assay, and therefore directly impacts the feasibility and the ease-of-use of a test in field settings. PMID- 27001470 TI - Prevalence and factors associated with potentially inappropriate prescriptions among older patients at hospital discharge. AB - RATIONALE, AIMS AND OBJECTIVES: Explicit criteria have been used worldwide to identify suboptimal prescribing such as potentially inappropriate prescriptions (PIPs). The objective of our study was to determine prevalence, types and factors associated with PIPs in older people discharged from an Albanian hospital. METHOD: Retrospective, cross-sectional study conducted among patients aged 60 years and more discharged from the Cardiology and Internal Medicine departments of the University Hospital Center 'Mother Theresa' Tirana during 2013. PIPs were identified by using Beers (2012 update) and STOPP criteria (2008 and 2014 versions). Chi-square analysis and Student Test were performed. Crude and adjusted odds ratios with their 95% confidence intervals were estimated by logistic regression analysis. RESULTS: Medical files for 319 patients were assessed. The median number of drugs prescribed was 7.8 (SD 2.2). PIPs prevalence at hospital discharge was 34.5% (95% CI 27.5-42.2%; 110 patients) according to both Beers and STOPP version 1 criteria. STOPP version 2 identified 201 (63.0%) patients with at least one PIP (95% CI 55.2-70.2%; 312 PIPs). The drugs more frequently involved in PIPs were aspirin, spironolactone, benzodiazepines, digoxin and methyldopa. The odds of having a PIP were higher in patients discharged from Internal Medicine (P < 0.005). The PIP index was 0.056%, 0.054% and 0.125% respectively for Beers, STOPP 2008 and STOPP 2014 criteria. A significant positive correlation was found between the number of prescribed drugs and PIP occurrence. CONCLUSIONS: Our study found that between one and two out of three older patients has at least one PIP among the treatment prescribed at hospital discharge, depending on the tool used for detection. The high frequency of PIPs suggests the urgent need for interventions to reduce them. PMID- 27001469 TI - Human eosinophil activin A synthesis and mRNA stabilization are induced by the combination of IL-3 plus TNF. AB - Eosinophils contribute to immune regulation and wound healing/fibrosis in various diseases, including asthma. Growing appreciation for the role of activin A in such processes led us to hypothesize that eosinophils are a source of this transforming growth factor-beta superfamily member. Tumor necrosis factor-alpha (TNF) induces activin A by other cell types and is often present at the site of allergic inflammation along with the eosinophil-activating common beta (betac) chain-signaling cytokines (interleukin (IL)-5, IL-3, granulocyte-macrophages colony-stimulating factor (GM-CSF)). Previously, we established that the combination of TNF plus a betac chain-signaling cytokine synergistically induces eosinophil synthesis of the remodeling enzyme matrix metalloproteinase-9. Therefore, eosinophils were stimulated ex vivo by these cytokines and in vivo through an allergen-induced airway inflammatory response. In contrast to IL-5+TNF or GM-CSF+TNF, the combination of IL-3+TNF synergistically induced activin A synthesis and release by human blood eosinophils. IL-3+TNF enhanced activin A mRNA stability, which required sustained signaling of pathways downstream of p38 and extracellular signal-regulated kinase mitogen-activated protein kinases. In vivo, following segmental airway allergen challenge of subjects with mild allergic asthma, activin A mRNA was upregulated in airway eosinophils compared with circulating eosinophils, and ex vivo, circulating eosinophils tended to release more activin A in response to IL-3+TNF. These data provide evidence that eosinophils release activin A and that this function is enhanced when eosinophils are present in an allergen-induced inflammatory environment. Moreover, these data provide the first evidence for posttranscriptional control of activin A mRNA. We propose that an environment rich in IL-3+TNF will lead to eosinophil-derived activin A, which has an important role in regulating inflammation and/or fibrosis. PMID- 27001471 TI - A randomized, double-blind, crossover, placebo-controlled clinical trial to assess effects of the single ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase on oral malodor. AB - BACKGROUND: The main components of oral malodor have been identified as volatile sulfur compounds (VSCs) including hydrogen sulfide (H2S) and methyl mercaptan (CH3SH). VSCs also play an important role in the progression of periodontal disease. The aim of the present study was to assess the effects of the single ingestion of a tablet containing 20 mg of lactoferrin, 2.6 mg of lactoperoxidase, and 2.6 mg of glucose oxidase on VSCs in the mouth. METHOD: Subjects with VSCs greater than the olfactory threshold in their mouth air ingested a test or placebo tablet in two crossover phases. The concentrations of VSCs were monitored at baseline and 10 and 30 min after ingestion of the tablets using portable gas chromatography. RESULTS: Thirty-nine subjects were included in the efficacy analysis based on a full analysis set (FAS). The concentrations of total VSCs and H2S at 10 min were significantly lower in the test group than in the placebo group (-0.246 log ng/10 ml [95 % CI -0.395 to -0.098], P = 0.002; -0.349 log ng/10 ml; 95 % CI -0.506 to -0.192; P < 0.001, respectively). In the subgroup analysis, a significant difference in the concentration of total VSCs between the groups was also observed when subjects were fractionated by sex (male or female) and age (20-55 or 56-65 years). The reducing effect on total VSCs positively correlated with the probing pocket depth (P = 0.035). CONCLUSIONS: These results suggest that the ingestion of a tablet containing lactoferrin, lactoperoxidase, and glucose oxidase has suppressive effects on oral malodor. TRIAL REGISTRATION: This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (number: UMIN000015140 , date of registration: 16/09/2014). PMID- 27001472 TI - Simultaneous Surface-Near and Solution Fluorescence Correlation Spectroscopy. AB - We report the first simultaneous measurement of surface-confined and solution fluorescence correlation spectroscopy (FCS). We use an optical configuration for tightly focused excitation and separate detection of light emitted below (undercritical angle fluorescence, UAF) and above (supercritical angle fluorescence, SAF) the critical angle of total internal reflection of the coverslip/sample interface. This creates two laterally coincident detection volumes which differ in their axial extent. While detection of far-field UAF emission producesa standard confocal volume, near-field-mediated SAF produces a highly surface-confined detection volume at the coverslip/sample interface which extends only ~200 nm into the sample. A characterization of the two detection volumes by FCS of free diffusion is presented and compared with analytical models and simulations. The presented FCS technique allows to determine bulk solution concentrations and surface-near concentrations at the same time. PMID- 27001474 TI - [The pathogenicity of somatic mutation to common tumors and developmental malformation of the nervous system]. AB - In the course of development, both endogenous and exogenous factors can cause DNA damage, which resulted in somatic mutations. It is recongnized that somatic mutations are the causation of many nervous cancers, the pathogenicity of somatic mutation in developmental malformation of nervous system is unknown yet. With the development of next generation sequencing (NGS), especially the clinical application of the whole-exome sequencing and the targeted massively parallel sequencing, the somatic mutations with low levels can be detected precisely. The detection of low-level and tissue-specific somatic mutation in patients enables researchers to re-recognize the contribution of somatic mutation to neurological disorders. In this review, we systematically summarize the pathogenicity and characteristics of the somatic mutations in the common tumors and developmental malformation of nervous system, and the new technologies to detect somatic mutation in order to extend our understanding of its genetic etiologies and identifying the new drug targets in the future. PMID- 27001473 TI - New insights into sex chromosome evolution in anole lizards (Reptilia, Dactyloidae). AB - Anoles are a clade of iguanian lizards that underwent an extensive radiation between 125 and 65 million years ago. Their karyotypes show wide variation in diploid number spanning from 26 (Anolis evermanni) to 44 (A. insolitus). This chromosomal variation involves their sex chromosomes, ranging from simple systems (XX/XY), with heterochromosomes represented by either micro- or macrochromosomes, to multiple systems (X1X1X2X2/X1X2Y). Here, for the first time, the homology relationships of sex chromosomes have been investigated in nine anole lizards at the whole chromosome level. Cross-species chromosome painting using sex chromosome paints from A. carolinensis, Ctenonotus pogus and Norops sagrei and gene mapping of X-linked genes demonstrated that the anole ancestral sex chromosome system constituted by microchromosomes is retained in all the species with the ancestral karyotype (2n = 36, 12 macro- and 24 microchromosomes). On the contrary, species with a derived karyotype, namely those belonging to genera Ctenonotus and Norops, show a series of rearrangements (fusions/fissions) involving autosomes/microchromosomes that led to the formation of their current sex chromosome systems. These results demonstrate that different autosomes were involved in translocations with sex chromosomes in closely related lineages of anole lizards and that several sequential microautosome/sex chromosome fusions lead to a remarkable increase in size of Norops sagrei sex chromosomes. PMID- 27001475 TI - [Advances on the profiling of 5-hydroxymethylcytosine]. AB - 5-hydroxymethylcytosine (5hmC) is a naturally existing component in mammalian genomic DNA and is regarded as the sixth DNA base. Accumulating studies have revealed the essential role of 5hmC in embryonic development, brain function and cancer research. Compared to another well-known cytosine methylation derivate, 5 methylcytosine (5mC), the detection of 5hmC is difficult for its lower lever existing in most tissues. To distinguish 5hmC from other cytosine derivates, the methods using chemical or enzymatic DNA treatment, have been applied in targeted 5hmC detection or non-targeted 5hmC enrichment. Therefore, profiling DNA hydroxymethylcytosine by sensitive, accurate and reliable method is crucial for epigenetic study. This review discusses the principles behind recently developed techniques for 5hmC quantification and mapping. By comparing the advantages and shortcomings of these methods, the general guidelines were provided on how to select appropriate methods for specific experimental contexts. PMID- 27001476 TI - [Application of CRISPR/Cas9 mediated genome editing in farm animals]. AB - CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) is an acquired immune system found in bacteria and archaea that fight against invasion of viruses or plasmids. CRISPR/Cas systems are currently classified into three main types: I, II and III, of which type II has relatively simple components. The CRISPR/Cas9 technology modified from type II CRISPR/Cas system has been developed as an efficient genome editing tool. Since the initial application of the CRISPR/Cas9 technology in mammals in 2013, the reports of this system for genomic editing has skyrocketed. Farm animals are not only economically important animals, but also ideal animal models for human diseases and biomedical studies. In this review, we summarize the applications of CRISPR/Cas9 in farm animals, briefly describe the off-target effects and the main solutions, and finally highlight the future perspectives of this technology. PMID- 27001477 TI - [The application of genome editing in identification of plant gene function and crop breeding]. AB - Plant genome can be modified via current biotechnology with high specificity and excellent efficiency. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system are the key engineered nucleases used in the genome editing. Genome editing techniques enable gene targeted mutagenesis, gene knock-out, gene insertion or replacement at the target sites during the endogenous DNA repair process, including non-homologous end joining (NHEJ) and homologous recombination (HR), triggered by the induction of DNA double-strand break (DSB). Genome editing has been successfully applied in the genome modification of diverse plant species, such as Arabidopsis thaliana, Oryza sativa, and Nicotiana tabacum. In this review, we summarize the application of genome editing in identification of plant gene function and crop breeding. Moreover, we also discuss the improving points of genome editing in crop precision genetic improvement for further study. PMID- 27001478 TI - [Identification and analysis of the NAC transcription factor family in Triticum urartu]. AB - NAC transcription factors are one of plant-specific gene families with diverse functions, and they regulate plant development, organ formation and stress responses. Currently, the researches about NAC transcription factors mainly focus on model plants, Arabidopsis and rice, whereas such studies are hardly reported in wheat and other plants. In this study, the full-length coding sequences (CDS) of NAC transcription factors from Triticum urartu (TuNAC) were identified through bioinformatic analysis. Their biological function, evolutionary relationship, gene duplication and chromosomal locations were further predicted and analyzed. The quantitative real-time PCR (qRT-PCR) assay was used to verify the expression pattern of abiotic-related TuNAC transcription factors. A total of 87 TuNAC transcription factors with full-length CDS were identified, which were divided into seven subgroups through phylogenetic analysis. Thirty-nine TuNAC transcription factors were located on seven chromosomes, and five pairs of TuNAC transcription factors were duplicated. The expression of four TuNAC transcription factors was consistently increased under diverse abiotic stress by qRT-PCR assay. Our study thus provides basis for further functional investigations of TuNAC transcription factors. PMID- 27001479 TI - [Genome-wide identification and expression analysis of the WRKY gene family in peach]. AB - The WRKY transcription factors are one of the largest families of transcriptional regulators and play diverse regulatory roles in biotic and abiotic stresses, plant growth and development processes. In this study, the WRKY DNA-binding domain (Pfam Database number: PF03106) downloaded from Pfam protein families database was exploited to identify WRKY genes from the peach (Prunus persica 'Lovell') genome using HMMER 3.0. The obtained amino acid sequences were analyzed with DNAMAN 5.0, WebLogo 3, MEGA 5.1, MapInspect and MEME bioinformatics softwares. Totally 61 peach WRKY genes were found in the peach genome. Our phylogenetic analysis revealed that peach WRKY genes were classified into three Groups: I, II and III. The WRKY N-terminal and C-terminal domains of Group I (group I-N and group I-C) were monophyletic. The Group II was sub-divided into five distinct clades (groupII-a, II-b, II-c, II-d and II-e). Our domain analysis indicated that the WRKY regions contained a highly conserved heptapeptide stretch WRKYGQK at its N-terminus followed by a zinc-finger motif. The chromosome mapping analysis showed that peach WRKY genes were distributed with different densities over 8 chromosomes. The intron-exon structure analysis revealed that structures of the WRKY gene were highly conserved in the peach. The conserved motif analysis showed that the conserved motifs 1, 2 and 3, which specify the WRKY domain, were observed in all peach WRKY proteins, motif 5 as the unknown domain was observed in group II-d, two WRKY domains were assigned to GroupI. SqRT-PCR and qRT-PCR results indicated that 16 PpWRKY genes were expressed in roots, stems, leaves, flowers and fruits at various expression levels. Our analysis thus identified the PpWRKY gene families, and future functional studies are needed to reveal its specific roles. PMID- 27001480 TI - A bridge too far. PMID- 27001481 TI - Trade-offs between salinity preference and antipredator behaviour in the euryhaline sailfin molly Poecilia latipinna. AB - Salinity preference and responses to predatory chemical cues were examined both separately and simultaneously in freshwater (FW) and saltwater (SW)-acclimated sailfin mollies Poecilia latipinna, a euryhaline species. It was hypothesized that P. latipinna would prefer FW over SW, move away from chemical cues from a crayfish predator, and favour predator avoidance over osmoregulation when presented with both demands. Both FW and SW-acclimated P. latipinna preferred FW and actively avoided predator cues. When presented with FW plus predator cues v. SW with no cues, P. latipinna were more often found in FW plus predator cues. These results raise questions pertaining to the potential osmoregulatory stress of salinity transitions in euryhaline fishes relative to the potential fitness benefits and whether euryhalinity is utilized for predator avoidance. This study sheds light on the potential benefits and consequences of being salt tolerant or intolerant and complicates the understanding of the selection pressures that have favoured the different osmoregulatory mechanisms among fishes. PMID- 27001482 TI - Cutaneous T-cell Lymphoma and Pruritus: The Expression of IL-31 and its Receptors in the Skin. AB - Approximately 88% of cutaneous T-cell lymphoma (CTCL) patients are affected by pruritus that responds poorly to current antipruritic therapies. Interleukin (IL) 31, a Th2 cytokine, has been found to be increased in the serum of CTCL patients and to correlate with itch severity. This study investigated the role of IL-31 and its receptors (IL-31 receptor-alpha [IL-31RA] and OSMRbeta) in the skin of CTCL patients with mild versus moderate/severe pruritus. Expression levels of IL 31, IL-31RA, and OSMRbeta in the skin were measured using immunohistochemistry and correlated to pruritus severity and disease stage. In CTCL patients with moderate/severe pruritus, IL-31 was significantly elevated in the epidermis and dermal infiltrate, while IL-31RA and OSMRbeta were significantly elevated only in the epidermis. Furthermore, epidermal IL-31 levels correlated to itch severity. These results show that IL-31 may play a role in CTCL pruritus by exerting indirect effects on sensory nerves through epidermal neoplastic T cells and keratinocytes to transmit itch. PMID- 27001483 TI - Investigation of the DNA damage response to SFOM-0046, a new small-molecule drug inducing DNA double-strand breaks. AB - 2-Ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) is a novel anticancer agent that arrests cell cycle in S-phase and causes DNA replication stress leading to the phosphorylation of H2AX into gamma-H2AX. First, using the M21, HT29, HT-1080 and HeLa cell lines, we confirmed that S-phase cell cycle arrest and gamma-H2AX foci induction by SFOM-0046 is a general mechanism occurring in diverse cancer cell lines. In addition to gamma-H2AX, SFOM-0046 activates preferentially ATR-Chk1 in M21 and HT29 cells while both ATR-Chk1 and ATM-Chk2 pathways are activated in HCT116 cells. Co-localization of SFOM-0046-induced 53BP1 foci with gamma-H2AX foci validates that the DNA damage generated corresponds to double-strand-breaks (DSBs). Consistent with an S-phase arrest, SFOM-0046 treatment induces RAD51 foci formation but not DNA-PKcs foci, confirming that homologous recombination is the major DSB repair pathway targeted by the drug. Furthermore, using isogenic HCT116 p53+/+ and HCT116 p53-/- cells, we showed that p53 plays a key role in the survival mechanism to SFOM-0046. Finally, SFOM-0046 exhibits a dose-dependent antitumor activity on human fibrosarcoma HT-1080 tumours grafted onto chick chorioallantoic membranes without showing embryo toxicity even at high doses. Altogether, our results highlight SFOM-0046 as a very promising drug that induces a replication stress response. PMID- 27001484 TI - Further insight into reproductive incompatibility between putative cryptic species of the Bemisia tabaci whitefly complex. AB - The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), with its global distribution and extensive genetic diversity, is now known to be a complex of over 35 cryptic species. However, a satisfactory resolution of the systematics of this species complex is yet to be achieved. Here, we designed experiments to examine reproductive compatibility among species with different levels of mitochondrial cytochrome oxidase I (mtCOI) divergence. The data show that putative species with mtCOI divergence of >8% between them consistently exhibited complete reproductive isolation. However, two of the putative species, Asia II 9 and Asia II 3, with mtCOI divergence of 4.47% between them, exhibited near complete reproductive compatibility in one direction of their cross, and partial reproductive compatibility in the other direction. Together with some recent reports on this topic from the literature, our data indicates that, while divergence in the mtCOI sequences provides a valid molecular marker for species delimitation in most clades, more genetic markers and more sophisticated molecular phylogeny will be required to achieve adequate delimitation of all species in this whitefly complex. While many attempts have been made to examine the reproductive compatibility among genetic groups of the B. tabaci complex, our study represents the first effort to conduct crossing experiments with putative species that were chosen with considerations of their genetic divergence. In light of the new data, we discuss the best strategy and protocols to conduct further molecular phylogenetic analysis and crossing trials, in order to reveal the overall pattern of reproductive incompatibility among species of this whitefly complex. PMID- 27001485 TI - Seven day services: how relevant is the junior doctors' contract? PMID- 27001486 TI - One-step growth of 3D CoNi2S4 nanorods and cross-linked NiCo2S4 nanosheet arrays on carbon paper as anodes for high-performance lithium ion batteries. AB - 3D CoNi2S4 and cross-linked NiCo2S4 arrays have been grown on carbon paper (CP) using a one-step hydrothermal method. The 3D cross-linked structure provides a convenient channel for electron and lithium-ion (Li(+)) transport and performs a facile strain relaxation during cycling, exhibits high capacity, excellent rate capability and superior cycle performance. PMID- 27001487 TI - Detection of a specific pattern of hyaluronan oligosaccharides and their binding proteins in human ovarian tumour. AB - Tumour cells generate hyaluronan (HA) oligomers (O-HA) by an autocrine mechanism to regulate their own behaviour through receptor interaction, necessitating analysis of HA sizes and its receptor expression in tumour progression. In this study for the first time, we identified specific size of HA in malignant ovarian tumour compared to benign tumour tissue. Therefore, we prepared the identified HA probes and conducted multiplex and monoplex ligand blot analysis and Immunohistochemistry to identify their receptor expression and distribution. Although, HA recognized CD44 as principle receptors despite of size, multiplex analysis showed multiple receptor expression with distribution at the tumour cell surface. Furthermore, the HA 6-mer (major O-HA of ovarian tumour) pull down of tumour tissue proteins showed 120 kDa protein along with CD44 with over expression in the malignant tumour. Upon depletion of CD44 protein HA 6-mer showed a major 120 kDa protein with distribution at nuclear membrane, suggesting that this protein may play an important role in ovarian tumour progression. In summary, ovarian tumour cells of different grade showed heterogeneity in generation of HA oligomers and their interaction with specific receptors. Therefore, simultaneous analysis of O-HA and their receptors expression could serve as a prognostic indicator during tumorigenesis. Copyright (c) 2016 John Wiley & Sons, Ltd. SIGNIFICANCE OF THE STUDY: Down regulation of hyaluronan (HA) at tumour epithelial cells results in the generation of O-HA. Increasing evidence about O-HA biological functions (mainly in vitro) are available, but we lack information of O-HA sizes generated during tumorigenesis and less information is available about their receptor interaction. We used biochemical approaches and identified that tumour cells of different grade possessing heterogeneity in generation of O-HA and specificity towards receptor binding. We identified a new receptor for HA 6-mer that over express in cancer tissue that shows its role in tumour progression. Collectively, simultaneous identification of HA sizes and their receptors could serve as a prognostic marker. PMID- 27001488 TI - Enhanced near-infrared photoresponse of organic phototransistors based on single component donor-acceptor conjugated polymer nanowires. AB - Single-component near-infrared phototransistors based on ambipolar organic semiconductor nanowires have been investigated and compared with their corresponding thin-film counterparts. The nanowire organic phototransistors (NW OPTs) showed photocurrent/dark-current ratios and photoresponsivities as high as 1.3 * 10(4) and 440 mA W(-1) for the p-type channel, and 3.3 * 10(4) and 70 mA W( 1) for the n-type channel, respectively, upon near-infrared illumination with an intensity of 47.1 mW cm(-2). These were much higher values compared to their thin film counterparts. The enhancement of the near-infrared photoresponse could be attributed to the larger trap density originating from the semiconductor/insulator interface and the semiconductor/air interface. The performance of NW-OPTs was demonstrated to open up new possibilities to improve the near-infrared photoresponse of single-component devices. PMID- 27001490 TI - Corrigendum. PMID- 27001489 TI - Diet analysis of small mammal pests: A comparison of molecular and microhistological methods. AB - Knowledge of what pest species are eating is important to determine their impact on stored food products and to plan management strategies accordingly. In this study, we investigated the food habits of 2 rodents, Rattus rattus (ship rat) and Mus musculus castaneus (house mouse) as well as an insectivore, Suncus murinus (shrew), present in human dwellings. Both a microhistological approach and a DNA barcoding approach were used in the present study. Following DNA extraction, amplification was performed using group-specific primers targeting birds, plants and invertebrates. Resulting polymerase chain reaction products were sequenced and analyzed to identify the different prey species present in the gut contents. The findings from the application of both techniques were in agreement, but the detection of prey type with each technique was different. The DNA barcoding approach gave greater species-level identification when compared to the microhistological method, especially for the invertebrate and avian prey. Overall, with both techniques, 23 prey taxa were identified in the gut contents of the 3 species, including 15 plants, 7 insects and a single bird species. We conclude that with a selection of suitable "barcode genes" and optimization of polymerase chain reaction protocols, DNA barcoding can provide more accurate and faster results. Prey detection from either technique alone can bias the dietary information. Hence, combining prey information of both microhistological analysis and DNA barcoding is recommended to study pest diet, especially if the pest is an omnivore or insectivore species. PMID- 27001491 TI - Challenges for Worldwide Harmonization of Newborn Screening Programs. AB - BACKGROUND: Inherited metabolic disorders (IMDs) are caused by a defect in a metabolic pathway, leading to malfunctioning metabolism and/or the accumulation of toxic intermediate metabolites. To date, hundreds of IMDs have been identified. Many of these diseases are potentially fatal conditions that are not apparent at birth. Newborn screening (NBS) programs involve the clinical and laboratory examination of neonates who exhibit no health problems, with the aim of discovering those infants who are, in fact, suffering from a treatable condition. CONTENT: In recent years, the introduction of tandem mass spectrometry has allowed the expansion of screening programs. However, this expansion has brought a high degree of heterogeneity in the IMDs tested among different NBS programs. An attempt to harmonize the metabolic conditions recommended to be screened has been carried out. Two uniform screening panels have been proposed in the US and European Union, by knowledgeable organizations. Here, we review current evidence-based processes to assess and expand NBS programs. We also discuss the IMDs that have recently been introduced in some screening programs, such as severe combined immunodeficiencies, lysosomal storage disorders, and adrenoleukodystrophy. SUMMARY: NBS programs have been an established public health function for more than 50 years to efficiently and cost-effectively identify neonates with severe conditions. However, NBS is not yet optimal. This review is intended to elucidate the current degree of harmonization of NBS programs worldwide as well as to describe the major controversial points and discuss the multiple challenges that must be confronted in expanded NBS strategies. PMID- 27001492 TI - Biological Variation: The Effect of Different Distributions on Estimated Within Person Variation and Reference Change Values. AB - BACKGROUND: Good estimates of within-person biological variation, CVI, are essential for diagnosing and monitoring patients and for setting analytical performance specifications. The aim of the present study was to use computer simulations to evaluate the impact of various measurement distributions on different methods for estimating CVI and reference change value (RCV). METHOD: Data were simulated on the basis of 3 models for distributions of the within person effect. We evaluated 3 different methods for estimating CVI: standard ANOVA, ln-ANOVA, and CV-ANOVA, and 3 different methods for calculating RCV: classic, ln-RCV, and a nonparametric method. We estimated CVI and RCV with the different methods and compared the results with the true values. RESULTS: The performance of the methods varied, depending on both the size of the CVI and the type of distributions. The CV-ANOVA model performed well for the estimation of CVI with all simulated data. The ln-RCV method performed best if data were ln normal distributed or CVI was less than approximately 12%. The nonparametric RCV method performed well for all simulated data but was less precise. CONCLUSIONS: The CV-ANOVA model is recommended for both calculation of CVI and the step-by step approach of checking for outliers and homogeneity in replicates and samples. The standard method for calculation of RCV should not be used when using CVs. PMID- 27001493 TI - Early-Phase Studies of Biomarkers: What Target Sensitivity and Specificity Values Might Confer Clinical Utility? AB - BACKGROUND: Many cancer biomarker research studies seek to develop markers that can accurately detect or predict future onset of disease. To design and evaluate these studies, one must specify the levels of accuracy sought. However, justified target levels are rarely available. METHODS: We describe a way to calculate target levels of sensitivity and specificity for a biomarker intended to be applied in a defined clinical context. The calculation requires knowledge of the prevalence or incidence of cases in the clinical population and the ratio of benefit associated with the clinical consequences of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average in the population, and they rely on some assumptions about uniformity of costs and benefits to those tested. RESULTS: Calculations are illustrated with 3 applications: predicting colon cancer recurrence in stage 1 patients; predicting interval breast cancer (between mammography screenings); and screening for ovarian cancer. CONCLUSIONS: It is feasible to specify target levels of biomarker performance that enable evaluation of the potential clinical impact of biomarkers in early-phase studies. Nevertheless, biomarkers meeting the criteria should still be tested rigorously in studies that measure the actual impact on patient outcomes of using the biomarker to make clinical decisions. PMID- 27001494 TI - Growth hormone receptor exon 3 isoforms may have no importance in the clinical setting of multiethnic Brazilian acromegaly patients. AB - BACKGROUND: Acromegaly is associated with significant morbidity and increased mortality, but has a variable severity phenotype. The presence of the exon 3 deleted isoform of the growth hormone receptor (d3-GHR) may influence the disease phenotype and treatment outcomes, including the frequency of biochemical discordance after medical treatment. AIMS: The objective of this study was to analyze the influence of the d3-GHR isoform on clinical and biochemical characteristics and in the treatment outcomes of Brazilian multiethnic acromegaly patients. METHODS: We retrospectively analyzed our acromegaly outpatient clinic databank and collected demographic, clinical, biochemical and treatment outcome data from those patients who agreed to participate in the study. A blood sample was collected from all patients, the DNA was extracted and the GHR isoforms were evaluated by PCR, with the full length (fl)-GHR represented by a 935-bp fragment and the d3-GHR represented by a 532-bp fragment. RESULTS: A total of 121 patients were included. Fifty-six patients (46.3 %) were full-length homozygous (fl/fl), 48 (39.7 %) were heterozygous (fl/d3) and 17 (14.0 %) were d3-GHR homozygous (d3/d3). There was no difference between patients homozygous for the fl isoform and those harboring at least one d3-GHR allele in the demographic, clinical and biochemical data or in the treatment outcomes, including somatostatin receptor ligands (SRL) monotherapy, combination therapy with SRL and cabergoline and pegvisomant treatment. There was also no difference between the groups for the frequency of GH and IGF-I discordance after medical treatment. CONCLUSION: GHR exon 3 genotyping appears to have no clinical significance, at least in Brazilian acromegaly patients. PMID- 27001496 TI - Formation of names of genera of prokaryotes that end on -oides or -opsis. A proposal for addenda to Rule 65(2) and Appendix 9 of the International Code of Nomenclature of Prokaryotes. AB - In view of the current confusion about the correct gender of genus names ending on -oides, and possible confusion in the future for genus names ending on -opsis, we propose non-retroactive addenda to Rule 65(2) and Appendix 9 of the International Code of Nomenclature of Prokaryotes so that new genera to be formed by adding the ending -oides to the stem of an existing genus name or another (Neo ) Latin word must be treated as neuter and genus names ending on -opsis are to be treated as feminine. PMID- 27001495 TI - Metabolic markers associated with insulin resistance predict type 2 diabetes in Koreans with normal blood pressure or prehypertension. AB - BACKGROUND: Questions remain as to the association between essential hypertension and increased incidence of type 2 diabetes (T2DM). The premise of this analysis is that insulin resistance/compensatory hyperinsulinemia is a major predictor of T2DM, and the greater the prevalence of insulin resistance within any population, normotensive or hypertensive, the more likely T2DM will develop. The hypothesis to be tested is that surrogate estimates of insulin resistance will predict incident T2DM to a significant degree in persons with normal blood pressure or prehypertension. METHODS: Analysis of data from a population-based survey of 10, 038 inhabitants of rural and urban areas of Korea, >=40 years-old, initiated in 2001, with measures of demographic and metabolic characteristics at baseline and 8-years later. Participants were classified as having normal blood pressure or prehypertension, and three simple manifestations of insulin resistance related to the pathophysiology of T2DM used to predict incident T2DM: (1) glycemia (plasma glucose concentration 2-hour after 75 g oral glucose challenge = 2-hour PG); (2) hyperinsulinemia (plasma insulin concentration 2-hour after 75 g oral glucose challenge = 2-hour PI); and (3) dyslipidemia (ratio of fasting plasma triglyceride/high/density lipoprotein cholesterol concentration = TG/HDL-C ratio). RESULTS: Fully adjusted hazard ratios (HR, 95 % CI) for incident T2DM were highest (P < 0.001) in the quartile of individuals with the highest 2-hour PG concentrations, ranging from 5.84 (3.37-10.1) in women with prehypertension to 12.2 (7.12-21.00) in men with normal blood pressure. T2DM also developed to a significantly greater degree in subjects within the highest quartile of TG/HDL-C ratios, with HRs varying from 2.91 (1.63-2.58) in women with prehypertension (P < 0.001) to 1.77 (1.12-2.81, P < 0.05) in men with prehypertension. The least predictive index of insulin resistance was the 2-hour PI concentration. Subjects with normal blood pressure in the highest quartile of 2-hour PI concentrations were significantly associated with incident T2DM, with HRs of 1.5 (1.02-2.20, P = 0.25) and 2.02 (1.35-3.02, P < 0.001), in men and women, respectively. Finally, incidence of T2DM in the highest quartile was somewhat greater in patients with prehypertension, irrespective of predictor. CONCLUSIONS: Metabolic variables associated with insulin resistance (glycemia, insulinemia, and dyslipidemia) predict the development of T2DM in patients with either normal blood pressure or prehypertension. PMID- 27001497 TI - Visual information representation and rapid-scene categorization are simultaneous across cortex: An MEG study. AB - Perceiving the visual world around us requires the brain to represent the features of stimuli and to categorize the stimulus based on these features. Incorrect categorization can result either from errors in visual representation or from errors in processes that lead to categorical choice. To understand the temporal relationship between the neural signatures of such systematic errors, we recorded whole-scalp magnetoencephalography (MEG) data from human subjects performing a rapid-scene categorization task. We built scene category decoders based on (1) spatiotemporally resolved neural activity, (2) spatial envelope (SpEn) image features, and (3) behavioral responses. Using confusion matrices, we tracked how well the pattern of errors from neural decoders could be explained by SpEn decoders and behavioral errors, over time and across cortical areas. Across the visual cortex and the medial temporal lobe, we found that both SpEn and behavioral errors explained unique variance in the errors of neural decoders. Critically, these effects were nearly simultaneous, and most prominent between 100 and 250ms after stimulus onset. Thus, during rapid-scene categorization, neural processes that ultimately result in behavioral categorization are simultaneous and co-localized with neural processes underlying visual information representation. PMID- 27001498 TI - Increased integrity of white matter pathways after dual n-back training. AB - Dual n-back WM training has been shown to produce broad transfer effects to different untrained cognitive functions. The task is demanding to the cognitive system because it includes a bi-modal (auditory and visual) dual-task component. A previous WM training study showed increased white matter integrity in the parietal lobe as well as the anterior part of the corpus callosum after visual n back training. We investigated dual n-back training-related changes in white matter pathways. We anticipated dual n-back training to increase white matter integrity in pathways that connect brain regions related to WM processes. Additionally, we hypothesized that dual n-back training would produce more brain wide white matter changes than single n-back training because of the involvement of two modalities and the additional dual-task coordination component of the task. The dual n-back training group showed increased white matter integrity (reflected as increased fractional anisotropy, FA) after training. The effects were mostly left lateralized as compared with changes from pretest to posttest in the passive and active control groups. Additionally, significant effects were observed in the anterior part of the corpus callosum, when the training group was compared with the passive control group. There were no changes in pretest to posttest FA changes between the passive and active control groups. The results therefore show that dual n-back training produces increased integrity in white matter pathways connecting different brain regions. The results are discussed in reference to the bi-modal dual-task component of the training task. PMID- 27001499 TI - Assessment of trait anxiety and prediction of changes in state anxiety using functional brain imaging: A test-retest study. AB - Anxiety is a multidimensional construct that includes stable trait anxiety and momentary state anxiety, which have a combined effect on our mental and physical well-being. However, the relationship between intrinsic brain activity and the feeling of anxiety, particularly trait and state anxiety, remain unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) (amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo)) to determine the effects of intrinsic brain activity on stable inter-individual trait anxiety and intra-individual state anxiety variability in a cross-sectional and test-retest study. We found that at both time points, the trait anxiety score was significantly associated with intrinsic brain activity (both the ALFF and ReHo) in the right ventral medial prefrontal cortex (vmPFC) and ALFF of the dorsal anterior cingulate cortex/anterior midcingulate cortex (dACC/aMCC). More importantly, the change in intrinsic brain activity in the right insula was predictive of intra-individual state anxiety variability over a 9-month interval. The test-retest nature of this study's design could provide an opportunity to distinguish between the intrinsic brain activity associated with state and trait anxiety. These results could deepen our understanding of anxiety from a neuroscientific perspective. PMID- 27001500 TI - Reduced functional segregation between the default mode network and the executive control network in healthy older adults: A longitudinal study. AB - The effects of age on functional connectivity (FC) of intrinsic connectivity networks (ICNs) have largely been derived from cross-sectional studies. Far less is known about longitudinal changes in FC and how they relate to ageing-related cognitive decline. We evaluated intra- and inter-network FC in 78 healthy older adults two or three times over a period of 4years. Using linear mixed modeling we found progressive loss of functional specialization with ageing, evidenced by a decline in intra-network FC within the executive control (ECN) and default mode networks (DMN). In contrast, longitudinal inter-network FC between ECN and DMN showed a u-shaped trajectory whereby functional segregation between these two networks initially increased over time and later decreased as participants aged. The rate of loss in functional segregation between ECN and DMN was associated with ageing-related decline in processing speed. The observed longitudinal FC changes and their associations with processing speed remained after correcting for longitudinal reduction in gray matter volume. These findings help connect ageing-related changes in FC with ageing-related decline in cognitive performance and underscore the value of collecting concurrent longitudinal imaging and behavioral data. PMID- 27001501 TI - Alpha suppression and connectivity modulations in left temporal and parietal cortices index partial awareness of words. AB - The partial awareness hypothesis is a theoretical proposal that recently provided a reconciling solution to graded and dichotomous accounts of consciousness. It suggests that we can become conscious of distinct properties of an object independently, ranging from low-level features to complex forms of representation. We investigated this hypothesis using classic visual word masking adapted to a near-threshold paradigm. The masking intensity was adjusted to the individual perception threshold, at which individual alphabetical letters, but not words, could be perceived in approximately half of the trials. We confined perception to a pre-lexical stage of word processing that corresponded to a clear condition of partial awareness. At this level of representation, the stimulus properties began to emerge within consciousness, yet they did not escalate to full stimulus awareness. In other words, participants were able to perceive individual letters, while remaining unaware of the whole letter strings presented. Cortical activity measured with MEG was compared between physically identical trials that differed in perception (perceived, not perceived). We found that compared to no awareness, partial awareness of words was characterized by suppression of oscillatory alpha power in left temporal and parietal cortices. The analysis of functional connectivity with seeds based on the power effect in these two regions revealed sparse connections for the parietal seed, and strong connections between the temporal seed and other regions of the language network. We suggest that the engagement of language regions indexed by alpha power suppression is responsible for establishing and maintaining conscious representations of individual pre-lexical units. PMID- 27001502 TI - Clinical Implications of Assisted Peak Cough Flow Measured With an External Glottic Control Device for Tracheostomy Decannulation in Patients With Neuromuscular Diseases and Cervical Spinal Cord Injuries: A Pilot Study. AB - OBJECTIVE: To investigate the clinical usefulness and significance of an external control device substituting for glottic function in determining the feasibility of decannulation in tracheostomized patients with neuromuscular diseases and cervical spinal cord injuries whose assisted peak cough flow (APCF) was unmeasurable or <160L/min. DESIGN: Before-after trial. SETTING: Inpatient setting in a university hospital. PARTICIPANTS: Tracheostomized patients (N=16; 11 with neuromuscular diseases and 5 with cervical spinal cord injuries) were recruited. INTERVENTIONS: Unassisted peak cough flow (UPCF) and APCF were measured with and without an external glottic control device. Among patients whose APCF without the device was <160L/min, if their APCF with the device was measured as >=160L/min, they were decannulated. After decannulation, UPCF and APCF were measured again. MAIN OUTCOME MEASURES: APCF with and without an external glottic control device as well as APCF after decannulation. RESULTS: After successful decannulation, APCFs were greater than or equal to those measured with the device before decannulation. No patients underwent intubation or retracheostomy, and there were no respiratory complications. CONCLUSIONS: The external glottic control device substituting for innate glottic function is beneficial for determining tracheostomy decannulation. It provides an objective and accurate APCF. It is particularly helpful for patients whose APCF is >=160L/min while using the device, even if APCF is <160L/min without this device. PMID- 27001503 TI - Response and resilience of soil microbial communities inhabiting in edible oil stress/contamination from industrial estates. AB - BACKGROUND: Gauging the microbial community structures and functions become imperative to understand the ecological processes. To understand the impact of long-term oil contamination on microbial community structure soil samples were taken from oil fields located in different industrial regions across Kadi, near Ahmedabad, India. Soil collected was hence used for metagenomic DNA extraction to study the capabilities of intrinsic microbial community in tolerating the oil perturbation. RESULTS: Taxonomic profiling was carried out by two different complementary approaches i.e. 16S rDNA and lowest common ancestor. The community profiling revealed the enrichment of phylum "Proteobacteria" and genus "Chromobacterium," respectively for polluted soil sample. Our results indicated that soil microbial diversity (Shannon diversity index) decreased significantly with contamination. Further, assignment of obtained metagenome reads to Clusters of Orthologous Groups (COG) of protein and Kyoto Encyclopedia of Genes and Genomes (KEGG) hits revealed metabolic potential of indigenous microbial community. Enzymes were mapped on fatty acid biosynthesis pathway to elucidate their roles in possible catalytic reactions. CONCLUSION: To the best of our knowledge this is first study for influence of edible oil on soil microbial communities via shotgun sequencing. The results indicated that long-term oil contamination significantly affects soil microbial community structure by acting as an environmental filter to decrease the regional differences distinguishing soil microbial communities. PMID- 27001504 TI - Young people's views about consenting to data linkage: findings from the PEARL qualitative study. AB - BACKGROUND: Electronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study. The Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. Qualitative research was incorporated in the PEARL study to examine participants' views about data linkage and inform approaches to information sharing. This paper focusses on issues of consent. METHODS: Digitally recorded interviews were conducted with 55 participants aged 17-19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach. RESULTS: Participant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with 'opt-in' consent through which participants are 'asked' if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented with different scenarios, and were sometimes inconsistent. CONCLUSIONS: Findings from this study question the validity of 'informed consent' as a cornerstone of good governance, and the extent to which potential research participants understand different types of consent and what they are consenting, or not consenting, to. Pragmatic, imaginative and flexible approaches are needed if research using data linkage is to successfully realise its potential for public good without undermining public trust in the research process. PMID- 27001505 TI - Hematopoietic Stem Cell Transplant for Primary Immunodeficiency Diseases: A Single-Center Experience. AB - OBJECTIVES: The only curative treatment for many patients with primary immunodeficiency disease is hematopoietic stem cell transplant. In this study, we report the transplant outcomes of patients with primary immunodeficiency diseases. MATERIALS AND METHODS: Herein, we present the transplant outcomes of 20 patients with primary immunodeficiency disease seen at our center in Kayseri, Turkey, from 2010 to 2015. RESULTS: The disease distribution of the 20 patients were as follows: 6 patients with severe combined immunodeficiency, 4 patients with hemophagocytic lymphohistiocytosis, 2 patients with chronic granulomatous disease, 2 patients with type 2 Griscelli syndrome, 2 patients with B-cell deficiency plus bone marrow failure, 1 patient with severe congenital neutropenia, 1 patient with X-linked lymphoproliferative disease, 1 patient with T-cell deficiency plus relapsed non-Hodgkin lymphoma, and 1 patient with type 1 leukocyte adhesion deficiency. Of the 20 patients, 11 received related HLA matched, 6 received haploidentical, 2 received unrelated HLA-matched, and 1 received HLA-mismatched transplant. The median age at transplant was 21 months, and median follow-up was 5 months. Overall survival rate was 65%. Mean engraftment times for neutrophils and platelets were 14.25 +/- 3.08 and 24.7 +/- 11.4 days. Graft-versus-host disease was observed in 30% of patients. CONCLUSIONS: Patients with primary immunodeficiency disease treated at our center had acceptable transplant outcomes. This study supports the use of hematopoietic stem cell transplant in patients with primary immunodeficiency disease. PMID- 27001506 TI - First-ever Reported Obstructing Ureteral Nephrogenic Adenoma in a Child and Subsequent Robotic-assisted Laparoscopic Ileal Ureter. AB - To report the first known case of a completely intracorporeal robotic-assisted laparoscopic ileal ureter in the pediatric population, a 12-year-old boy with near-complete replacement of his right ureter with nephrogenic adenoma and resulting debilitating renal colic. Intracorporeal robotic-assisted laparoscopic ileal ureter was performed without complication. A detailed description of our surgical technique is included. The patient had improvement in hydronephrosis and complete resolution of renal colic symptoms with minimal incisional length compared to traditional laparotomy. Intracorporeal robotic-assisted laparoscopic ileal ureter provides the benefits of minimally invasive surgery when complete ureteral replacement is needed. PMID- 27001507 TI - ESR study of molecular orientation and dynamics of TEMPO derivatives in CLPOT 1D nanochannels. AB - The molecular orientations and dynamics of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) radical derivatives with large substituent groups at the 4-position (4-X TEMPO) in the organic one-dimensional nanochannels within the nanosized molecular template 2,4,6-tris(4-chlorophenoxy)-1,3,5-triazine (CLPOT) were examined using ESR. The concentrations of guest radicals, including 4-methoxy-TEMPO (MeO-TEMPO) or 4-oxo-TEMPO (TEMPONE), in the CLPOT nanochannels in each inclusion compound (IC) were reduced by co-including 4-substituted-2,2,6,6-tetramethylpiperidine (4 R-TEMP) compounds at a ratio of 1 : 30-1 : 600. At higher temperatures, the guest radicals in each IC underwent anisotropic rotational diffusion in the CLPOT nanochannels. The rotational diffusion activation energy, Ea , associated with MeO-TEMPO or TEMPONE in the CLPOT nanochannels (6-7 kJ mol(-1) ), was independent of the size and type of substituent group and was similar to the Ea values obtained for TEMPO and 4- hydroxy-TEMPO (TEMPOL) in our previous study. However, in the case in which TEMP was used as a guest compound for dilution (spacer), the tilt of the rotational axis to the principal axis system of the g-tensor, and the rotational diffusion correlation time, tauR , of each guest radical in the CLPOT nanochannels were different from the case with other 4-R-TEMP. These results indicate the possibility of controlling molecular orientation and dynamics of guest radicals in CLPOT ICs through the appropriate choice of spacer. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001508 TI - 'Modulation of the enzymatic activities of replicative helicase (DnaB) by interaction with Hp0897: a possible mechanism for helicase loading in Helicobacter pylori'. AB - DNA replication in Helicobacter pylori is initiated from a unique site (oriC) on its chromosome where several proteins assemble to form a functional replisome. The assembly of H. pylori replication machinery is similar to that of the model gram negative bacterium Escherichia coli except for the absence of DnaC needed to recruit the hexameric DnaB helicase at the replisome assembly site. In the absence of an obvious DnaC homologue inH. pylori, the question arises as to whether HpDnaB helicase is loaded at theHp-replication origin by itself or is assisted by other unidentified protein(s). A high-throughput yeast two-hybrid study has revealed two proteins of unknown functions (Hp0897 and Hp0340) that interact with HpDnaB. Here we demonstrate that Hp0897 interacts with HpDnaB helicase in vitro as well as in vivo Furthermore, the interaction stimulates the DNA binding activity of HpDnaB and modulates its adenosine triphosphate hydrolysis and helicase activities significantly. Prior complex formation of Hp0897 and HpDnaB enhances the binding/loading of DnaB onto DNA. Hp0897, along with HpDnaB, colocalizes with replication complex at initiation but does not move with the replisome during elongation. Together, these results suggest a possible role of Hp0897 in loading of HpDnaB at oriC. PMID- 27001509 TI - Mechanism of fusidic acid inhibition of RRF- and EF-G-dependent splitting of the bacterial post-termination ribosome. AB - The antibiotic drug fusidic acid (FA) is commonly used in the clinic against gram positive bacterial infections. FA targets ribosome-bound elongation factor G (EF G), a translational GTPase that accelerates both messenger RNA (mRNA) translocation and ribosome recycling. How FA inhibits translocation was recently clarified, but FA inhibition of ribosome recycling by EF-G and ribosome recycling factor (RRF) has remained obscure. Here we use fast kinetics techniques to estimate mean times of ribosome splitting and the stoichiometry of GTP hydrolysis by EF-G at varying concentrations of FA, EF-G and RRF. These mean times together with previous data on uninhibited ribosome recycling were used to clarify the mechanism of FA inhibition of ribosome splitting. The biochemical data on FA inhibition of translocation and recycling were used to model the growth inhibitory effect of FA on bacterial populations. We conclude that FA inhibition of translocation provides the dominant cause of bacterial growth reduction, but that FA inhibition of ribosome recycling may contribute significantly to FA induced expression of short regulatory open reading frames, like those involved in FA resistance. PMID- 27001510 TI - Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1. AB - DNA damage tolerance (DDT) is responsible for genomic stability and cell viability by bypassing the replication block. In Saccharomyces cerevisiae DDT employs two parallel branch pathways to bypass the DNA lesion, namely translesion DNA synthesis (TLS) and error-free lesion bypass, which are mediated by sequential modifications of PCNA. Rad5 has been placed in the error-free branch of DDT because it contains an E3 ligase domain required for PCNA polyubiquitination. Rad5 is a multi-functional protein and may also play a role in TLS, since it interacts with the TLS polymerase Rev1. In this study we mapped the Rev1-interaction domain in Rad5 to the amino acid resolution and demonstrated that Rad5 is indeed involved in TLS possibly through recruitment of Rev1. Genetic analyses show that the dual functions of Rad5 can be separated and reconstituted. Crystal structure analysis of the Rad5-Rev1 interaction reveals a consensus RFF motif in the Rad5 N-terminus that binds to a hydrophobic pocket within the C terminal domain of Rev1 that is highly conserved in eukaryotes. This study indicates that Rad5 plays a critical role in pathway choice between TLS and error free DDT. PMID- 27001511 TI - Nonsense-mediated decay regulates key components of homologous recombination. AB - Cells frequently experience DNA damage that requires repair by homologous recombination (HR). Proteins involved in HR are carefully coordinated to ensure proper and efficient repair without interfering with normal cellular processes. In Saccharomyces cerevisiae, Rad55 functions in the early steps of HR and is regulated in response to DNA damage through phosphorylation by the Mec1 and Rad53 kinases of the DNA damage response. To further identify regulatory processes that target HR, we performed a high-throughput genetic interaction screen with RAD55 phosphorylation site mutants. Genes involved in the mRNA quality control process, nonsense-mediated decay (NMD), were found to genetically interact with rad55 phospho-site mutants. Further characterization revealed that RAD55 transcript and protein levels are regulated by NMD. Regulation of HR by NMD extends to multiple targets beyond RAD55, including RAD51, RAD54 and RAD57 Finally, we demonstrate that loss of NMD results in an increase in recombination rates and resistance to the DNA damaging agent methyl methanesulfonate, suggesting this pathway negatively regulates HR under normal growth conditions. PMID- 27001512 TI - The Hsp70 homolog Ssb and the 14-3-3 protein Bmh1 jointly regulate transcription of glucose repressed genes in Saccharomyces cerevisiae. AB - Chaperones of the Hsp70 family interact with a multitude of newly synthesized polypeptides and prevent their aggregation. Saccharomyces cerevisiae cells lacking the Hsp70 homolog Ssb suffer from pleiotropic defects, among others a defect in glucose-repression. The highly conserved heterotrimeric kinase SNF1/AMPK (AMP-activated protein kinase) is required for the release from glucose repression in yeast and is a key regulator of energy balance also in mammalian cells. When glucose is available the phosphatase Glc7 keeps SNF1 in its inactive, dephosphorylated state. Dephosphorylation depends on Reg1, which mediates targeting of Glc7 to its substrate SNF1. Here we show that the defect in glucose repression in the absence of Ssb is due to the ability of the chaperone to bridge between the SNF1 and Glc7 complexes. Ssb performs this post-translational function in concert with the 14-3-3 protein Bmh, to which Ssb binds via its very C-terminus. Raising the intracellular concentration of Ssb or Bmh enabled Glc7 to dephosphorylate SNF1 even in the absence of Reg1. By that Ssb and Bmh efficiently suppressed transcriptional deregulation of Deltareg1 cells. The findings reveal that Ssb and Bmh comprise a new chaperone module, which is involved in the fine tuning of a phosphorylation-dependent switch between respiration and fermentation. PMID- 27001513 TI - Distinct genetic control of homologous recombination repair of Cas9-induced double-strand breaks, nicks and paired nicks. AB - DNA double-strand breaks (DSBs) are known to be powerful inducers of homologous recombination (HR), but single-strand breaks (nicks) have also been shown to trigger HR. Both DSB- and nick-induced HR ((nick)HR) are exploited in advanced genome-engineering approaches based on the bacterial RNA-guided nuclease Cas9. However, the mechanisms of (nick)HR are largely unexplored. Here, we applied Cas9 nickases to study (nick)HR in mammalian cells. We find that (nick)HR is unaffected by inhibition of major damage signaling kinases and that it is not suppressed by nonhomologous end-joining (NHEJ) components, arguing that nick processing does not require a DSB intermediate to trigger HR. Relative to a single nick, nicking both strands enhances HR, consistent with a DSB intermediate, even when nicks are induced up to ~1kb apart. Accordingly, HR and NHEJ compete for repair of these paired nicks, but, surprisingly, only when 5' overhangs or blunt ends can be generated. Our study advances the understanding of molecular mechanisms driving nick and paired-nick repair in mammalian cells and clarify phenomena associated with Cas9-mediated genome editing. PMID- 27001514 TI - Novel glycylated sugar alcohols protect ESC-specific microRNAs from degradation in iPS cells. AB - Excessive accumulation of embryonic stem cell (ESC)-specific microRNAs occurs in both ESCs and induced pluripotent stem cells (iPSC); yet, the mechanism involved is unknown. In iPSCs, we for the first time found that novel glycylated sugar alcohols, particularly glycylglycerins, are tightly bound with ESC-specific microRNA precursors (pre-miRNA), such as pre-miR-302. Among these isolated glycylglycerins, we further identified that 1,3-diglycylglycerin and 1,2,3 triglycylglycerin are two major compounds bonded with negatively charged nucleic acids via electro-affinity and subsequently forming sugar-like coats in the hairpin-like double helix structures of pre-miRNAs. As a result, such glycylglycerin-formed coating serves as a protection layer against miRNA degradation. Moreover, we found that the pH value of iPSC cytosol determines the charges of these glycylglycerins. During iPSC differentiation, the cytosol pH is increased and hence neutralizes the charges of glycylglycerins, consequently leading to fast miRNA degradation. Therefore, the current findings not only explain how ESC-specific miRNAs are preserved and accumulated in iPSCs and ESCs but also demonstrate an important function of glycylglycerins in protecting the structural integrity of highly degradable miRNAs, providing a useful means for maintaining miRNA/siRNA function as well as developing the related RNA interference (RNAi) applications. PMID- 27001515 TI - Novel modes of RNA editing in mitochondria. AB - Gene structure and expression in diplonemid mitochondria are unparalleled. Genes are fragmented in pieces (modules) that are separately transcribed, followed by the joining of module transcripts to contiguous RNAs. Some instances of unique uridine insertion RNA editing at module boundaries were noted, but the extent and potential occurrence of other editing types remained unknown. Comparative analysis of deep transcriptome and genome data from Diplonema papillatum mitochondria reveals ~220 post-transcriptional insertions of uridines, but no insertions of other nucleotides nor deletions. In addition, we detect in total 114 substitutions of cytosine by uridine and adenosine by inosine, amassed into unusually compact clusters. Inosines in transcripts were confirmed experimentally. This is the first report of adenosine-to-inosine editing of mRNAs and ribosomal RNAs in mitochondria. In mRNAs, editing causes mostly amino-acid additions and non-synonymous substitutions; in ribosomal RNAs, it permits formation of canonical secondary structures. Two extensively edited transcripts were compared across four diplonemids. The pattern of uridine-insertion editing is strictly conserved, whereas substitution editing has diverged dramatically, but still rendering diplonemid proteins more similar to other eukaryotic orthologs. We posit that RNA editing not only compensates but also sustains, or even accelerates, ultra-rapid evolution of genome structure and sequence in diplonemid mitochondria. PMID- 27001516 TI - Ribosome hibernation factor promotes Staphylococcal survival and differentially represses translation. AB - In opportunistic Gram-positive Staphylococcus aureus, a small protein called hibernation-promoting factor (HPFSa) is sufficient to dimerize 2.5-MDa 70S ribosomes into a translationally inactive 100S complex. Although the 100S dimer is observed in only the stationary phase in Gram-negative gammaproteobacteria, it is ubiquitous throughout all growth phases in S. aureus The biological significance of the 100S ribosome is poorly understood. Here, we reveal an important role of HPFSa in preserving ribosome integrity and poising cells for translational restart, a process that has significant clinical implications for relapsed staphylococcal infections. We found that the hpf null strain is severely impaired in long-term viability concomitant with a dramatic loss of intact ribosomes. Genome-wide ribosome profiling shows that eliminating HPFSa drastically increased ribosome occupancy at the 5' end of specific mRNAs under nutrient-limited conditions, suggesting that HPFSa may suppress translation initiation. The protective function of HPFSa on ribosomes resides at the N terminal conserved basic residues and the extended C-terminal segment, which are critical for dimerization and ribosome binding, respectively. These data provide significant insight into the functional consequences of 100S ribosome loss for protein synthesis and stress adaptation. PMID- 27001517 TI - Pif1 removes a Rap1-dependent barrier to the strand displacement activity of DNA polymerase delta. AB - Using an in vitro reconstituted system in this work we provide direct evidence that the yeast repressor/activator protein 1 (Rap1), tightly bound to its consensus site, forms a strong non-polar barrier for the strand displacement activity of DNA polymerase delta. We propose that relief of inhibition may be mediated by the activity of an accessory helicase. To this end, we show that Pif1, a 5'-3' helicase, not only stimulates the strand displacement activity of Pol delta but it also allows efficient replication through the block, by removing bound Rap1 in front of the polymerase. This stimulatory activity of Pif1 is not limited to the displacement of a single Rap1 molecule; Pif1 also allows Pol delta to carry out DNA synthesis across an array of bound Rap1 molecules that mimics a telomeric DNA-protein assembly. This activity of Pif1 represents a novel function of this helicase during DNA replication. PMID- 27001518 TI - Inducible DamID systems for genomic mapping of chromatin proteins in Drosophila. AB - Dam identification (DamID) is a powerful technique to generate genome-wide maps of chromatin protein binding. Due to its high sensitivity, it is particularly suited to study the genome interactions of chromatin proteins in small tissue samples in model organisms such as Drosophila Here, we report an intein-based approach to tune the expression level of Dam and Dam-fusion proteins in Drosophila by addition of a ligand to fly food. This helps to suppress possible toxic effects of Dam. In addition, we describe a strategy for genetically controlled expression of Dam in a specific cell type in complex tissues. We demonstrate the utility of the latter by generating a glia-specific map of Polycomb in small samples of brain tissue. These new DamID tools will be valuable for the mapping of binding patterns of chromatin proteins in Drosophila tissues and especially in cell lineages. PMID- 27001519 TI - Rbfox proteins regulate microRNA biogenesis by sequence-specific binding to their precursors and target downstream Dicer. AB - Rbfox proteins regulate tissue-specific splicing by targeting a conserved GCAUG sequence within pre-mRNAs. We report here that sequence-specific binding of the conserved Rbfox RRM to miRNA precursors containing the same sequence motif in their terminal loops, including miR-20b and miR-107, suppresses their nuclear processing. The structure of the complex between precursor miR-20b and Rbfox RRM shows the molecular basis for recognition, and reveals changes in the stem-loop upon protein binding. In mammalian cells, Rbfox2 downregulates mature miR-20b and miR-107 levels and increases the expression of their downstream targets PTEN and Dicer, respectively, suggesting that Rbfox2 indirectly regulates many more cellular miRNAs. Thus, some of the widespread cellular functions of Rbfox2 protein are attributable to regulation of miRNA biogenesis, and might include the mis-regulation of miR-20b and miR-107 in cancer and neurodegeneration. PMID- 27001520 TI - Functional annotation of the vlinc class of non-coding RNAs using systems biology approach. AB - Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlinc RNAs genes likely function in cisto activate nearby genes. This effect while most pronounced in closely spaced vlinc RNA-gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlinc RNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non coding RNAs. PMID- 27001521 TI - Influence of major-groove chemical modifications of DNA on transcription by bacterial RNA polymerases. AB - DNA templates containing a set of base modifications in the major groove (5 substituted pyrimidines or 7-substituted 7-deazapurines bearing H, methyl, vinyl, ethynyl or phenyl groups) were prepared by PCR using the corresponding base modified 2'-deoxyribonucleoside triphosphates (dNTPs). The modified templates were used in an in vitro transcription assay using RNA polymerase from Bacillus subtilis and Escherichia coli Some modified nucleobases bearing smaller modifications (H, Me in 7-deazapurines) were perfectly tolerated by both enzymes, whereas bulky modifications (Ph at any nucleobase) and, surprisingly, uracil blocked transcription. Some middle-sized modifications (vinyl or ethynyl) were partly tolerated mostly by the E. colienzyme. In all cases where the transcription proceeded, full length RNA product with correct sequence was obtained indicating that the modifications of the template are not mutagenic and the inhibition is probably at the stage of initiation. The results are promising for the development of bioorthogonal reactions for artificial chemical switching of the transcription. PMID- 27001522 TI - Enrichment of IFN-gamma producing cells in different murine adipose tissue depots upon infection with an apicomplexan parasite. AB - Here we report that lean mice infected with the intracellular parasite Neospora caninum show a fast but sustained increase in the frequency of IFN-gamma producing cells noticeable in distinct adipose tissue depots. Moreover, IFN-gamma mediated immune memory could be evoked in vitro in parasite antigen-stimulated adipose tissue stromal vascular fraction cells collected from mice infected one year before. Innate or innate-like cells such as NK, NK T and TCRgammadelta(+) cells, but also CD4(+) and CD8(+) TCRbeta(+) lymphocytes contributed to the IFN gamma production observed since day one of infection. This early cytokine production was largely abrogated in IL-12/IL23 p40-deficient mice. Moreover, production of IFN-gamma by stromal vascular fraction cells isolated from these mice was markedly lower than that of wild-type counterparts upon stimulation with parasite antigen. In wild-type mice the increased IFN-gamma production was concomitant with up-regulated expression of genes encoding interferon-inducible GTPases and nitric oxide synthase, which are important effector molecules in controlling intracellular parasite growth. This increased gene expression was markedly impaired in the p40-deficient mice. Overall, these results show that NK cells but also diverse T cell populations mediate a prompt and widespread production of IFN-gamma in the adipose tissue of N. caninum infected mice. PMID- 27001523 TI - Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma. AB - Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology. PMID- 27001524 TI - The use, publication and future directions of immunocytochemistry in veterinary medicine: a consensus of the Oncology-Pathology Working Group. AB - One of the primary objectives of the Oncology Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for oncologic pathology. Consensus is established through review of relevant peer reviewed literature relative to a subgroup's particular focus. In this document, the authors provide descriptions of the literature reviewed, the review process, and a summary of the information gathered on immunocytochemistry. The intent of this publication is to help educate practitioners and pathologists on the process of immunocytochemistry and to provide a guide for the use of this technique in veterinary medicine. This document represents the opinions of the working group and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society. PMID- 27001525 TI - Hypercapnic acidosis attenuates pulmonary epithelial stretch-induced injury via inhibition of the canonical NF-kappaB pathway. AB - BACKGROUND: Hypercapnia, with its associated acidosis (HCA), is a consequence of respiratory failure and is also seen in critically ill patients managed with conventional "protective" ventilation strategies. Nuclear factor kappa-B (NF kappaB), a pivotal transcription factor, is activated in the setting of injury and repair and is central to innate immunity. We have previously established that HCA protects against ventilation-induced lung injury in vivo, potentially via a mechanism involving inhibition of NF-kappaB signaling. We wished to further elucidate the role and mechanism of HCA-mediated inhibition of the NF-kappaB pathway in attenuating stretch-induced injury in vitro. METHODS: Initial experiments examined the effect of HCA on cyclic stretch-induced inflammation and injury in human bronchial and alveolar epithelial cells. Subsequent experiments examined the role of the canonical NF-kappaB pathway in mediating stretch-induced injury and the mechanism of action of HCA. The contribution of pH versus CO2 in mediating this effect of HCA was also examined. RESULTS: Pulmonary epithelial high cyclic stretch (22 % equibiaxial strain) activated NF-kappaB, enhanced interleukin-8 (IL-8) production, caused cell injury, and reduced cell survival. In contrast, physiologic stretch (10 % strain) did not activate inflammation or cause cell injury. HCA reduced cyclic mechanical stretch-induced NF-kappaB activation, attenuated IL-8 production, reduced injury, and enhanced survival, in bronchial and alveolar epithelial cells, following shorter (24 h) and longer (120 h) cyclic mechanical stretch. Pre-conditioning with HCA was less effective than when HCA was applied after commencement of cell stretch. HCA prevented the stretch-induced breakdown of the NF-kappaB cytosolic inhibitor IkappaBalpha, while IkappaBalpha overexpression "occluded" the effect of HCA. These effects were mediated by a pH-dependent mechanism rather than via CO2 per se. CONCLUSIONS: HCA attenuates adverse mechanical stretch-induced epithelial injury and death, via a pH-dependent mechanism that inhibits the canonical NF-kappaB activation by preventing IkappaBalpha breakdown. PMID- 27001526 TI - Body size and meta-community structure: the allometric scaling of parasitic worm communities in their mammalian hosts. AB - In this paper we derive from first principles the expected body sizes of the parasite communities that can coexist in a mammal of given body size. We use a mixture of mathematical models and known allometric relationships to examine whether host and parasite life histories constrain the diversity of parasite species that can coexist in the population of any host species. The model consists of one differential equation for each parasite species and a single density-dependent nonlinear equation for the affected host under the assumption of exploitation competition. We derive threshold conditions for the coexistence and competitive exclusion of parasite species using invasion criteria and stability analysis of the resulting equilibria. These results are then used to evaluate the range of parasites species that can invade and establish in a target host and identify the 'optimal' size of a parasite species for a host of a given body size; 'optimal' is defined as the body size of a parasite species that cannot be outcompeted by any other parasite species. The expected distributions of parasites body sizes in hosts of different sizes are then compared with those observed in empirical studies. Our analysis predicts the relative abundance of parasites of different size that establish in the host and suggests that increasing the ratio of parasite body size to host body size above a minimum threshold increases the persistence of the parasite population. PMID- 27001527 TI - Shell-isolated nanoparticle-enhanced Raman spectroscopy study of the adsorption behaviour of DNA bases on Au(111) electrode surfaces. AB - For the first time, we used the electrochemical shell-isolated nanoparticle enhanced Raman spectroscopy (EC-SHINERS) technique to in situ characterize the adsorption behaviour of four DNA bases (adenine, guanine, thymine, and cytosine) on atomically flat Au(111) electrode surfaces. The spectroscopic results of the various molecules reveal similar features, such as the adsorption-induced reconstruction of the Au(111) surface and the drastic Raman intensity reduction of the ring breathing modes after the lifting reconstruction. As a preliminary study of the photo-induced charge transfer (PICT) mechanism, the in situ spectroscopic results obtained on single crystal surfaces are excellently illustrated with electrochemical data. PMID- 27001528 TI - Where is the leak in the pipeline? Investigating gender differences in academic promotion at an academic medical centre. AB - BACKGROUND: Women are still under-represented in the senior ranks of academic medicine. As local surveys represent a critical initial step in addressing the challenges of gender disparities in academic promotion within institutions, we surveyed faculty at an academic medical centre to identify factors to improve the academic advancement of women. METHODS: We conducted an electronic survey of all full-time faculty members in a Department of Medicine assessing academic rank and factors important in consideration for promotion. RESULTS: 106 faculty members (46 %) responded to the survey; 40 % of the respondents were women. There was a statistically significant gender gap in faculty rank (p = 0.002), with only 2 of 17 full professor positions occupied by women. Among faculty who had not yet requested promotion, women were more likely to report that they did not think an academic promotion would benefit them (69 vs. 32 % in men, p = 0.01), and to report a lack of encouragement for requesting promotion (50 vs. 29 %, p = 0.08). CONCLUSIONS: Targeting the perceived value of academic promotion among women faculty, increasing junior faculty mentorship and modifying annual review processes could address gender disparities in academic medicine ranks. PMID- 27001529 TI - Core size determination and structural characterization of intravenous iron complexes by cryogenic transmission electron microscopy. AB - Understanding physicochemical properties of intravenous (IV) iron drug products is essential to ensure the manufacturing process is consistent and streamlined. The history of physicochemical characterization of IV iron complex formulations stretches over several decades, with disparities in iron core size and particle morphology as the major source of debate. One of the main reasons for this controversy is room temperature sample preparation artifacts, which affect accurate determination of size, shape and agglomeration/aggregation of nanoscale iron particles. The present study is first to report the ultra-fine iron core structures of four IV iron complex formulations, sodium ferric gluconate, iron sucrose, low molecular weight iron dextran and ferumoxytol, using a cryogenic transmission electron microscopy (cryo-TEM) preservation technique, as opposed to the conventional room temperature (RT-TEM) technique. Our results show that room temperature preparation causes nanoparticle aggregation and deformation, while cryo-TEM preserves IV iron colloidal suspension in their native frozen-hydrated and undiluted state. In contrast to the current consensus in literature, all four IV iron colloids exhibit a similar morphology of their iron oxide cores with a spherical shape, narrow size distribution and an average size of 2nm. Moreover, out of the four tested formulations, ferumoxytol exhibits a cluster-like community of several iron carbohydrate particles which likely accounts for its large hydrodynamic size of 25nm, measured with dynamic light scattering. Our findings outline a suitable method for identifying colloidal nanoparticle core size in the native state, which is increasingly important for manufacturing and design control of complex drug formulations, such as IV iron drug products. PMID- 27001530 TI - An industrial perspective on the design and development of medicines for older patients. AB - An increasing elderly population is leading to a change in the global demographics. This presents a new challenge to society and the pharmaceutical industry. This demographic shift is providing an opportunity for the pharmaceutical industry to meet the specific needs of the changing patient population. One issue that has been identified is defining what is meant by "an older patient", since this definition cannot be simply limited to chronological age. The fundamental purpose of the design and development process is to create a product that can be used by the patient group in a safe and efficacious manner. In the pharmaceutical industry ICH Q8 is used to guide the design and development of medicines. The process leads to the definition of the Quality Target Product Profile (QTPP) for a specific drug product and patient population. One can imagine a product with various presentations described in the QTPP which suit paediatrics, adults and older patients. It is recognised that designing medicines for smaller population groups will result in multiple presentations that could lead to smaller manufacturing batch sizes. In the short to medium term; dose flexibility, easy-to-swallow formulations, and easier access packaging are all factors under consideration. Dose flexibility could be achieved with various dosage forms such as oral liquids, mini-tablets, or multi-particulates. Whilst patient dosage preferences are beginning to be understood, further investigation is needed to balance the needs of the patient, care giver, prescriber, and payer. There also remain a number of challenges with the engineering solutions and delivery device for mini-tablets and multi-particulates (aside from filled capsules) to accurately and robustly deliver the dose, and issues with handling the device and the packaging for an older patient. It is also recognised that there are numerous challenges, not least of which is the definition of the older patient and a generic QTPP for an older patients' drug product. It is likely that there will be no simple solution or 'one-size-fits-all' approach in drug product development to resolve the complex issues presented by the ageing population. PMID- 27001531 TI - Physiological function and inflamed-brain migration of mouse monocyte-derived macrophages following cellular uptake of superparamagnetic iron oxide nanoparticles-Implication of macrophage-based drug delivery into the central nervous system. AB - This study was designed to use superparamagnetic iron oxide nanoparticles (SPIONs) as evaluating tools to study monocyte-derived macrophages (MDM)-mediated delivery of small molecular agents into the diseased brains. MDM were tested with different-configured SPIONs at selected concentrations for their impacts on carrier cells' physiological and migratory properties, which were found to depend largely on particle size, coating, and treatment concentrations. SHP30, a SPION of 30-nm core size with oleic acids plus amphiphilic polymer coating, was identified to have high cellular uptake efficiency and cause little cytotoxic effects on MDM. At lower incubation dose (25MUg/mL), few alteration was observed in carrier cells' physiological and in vivo migratory functions, as tested in a lipopolysaccharide-induced acute neuroinflammation mouse model. Nevertheless, significant increase in monocyte-to-macrophage differentiation, and decrease in in vivo carrier MDM inflamed-brain homing ability were found in groups treated with a higher dose of SHP30at 100MUg/mL. Overall, our results have identified MDM treatment at 25MUg/mL SHP30 resulted in little functional changes, provided valuable parameters for using SPIONs as evaluating tools to study MDM-mediated therapeutics carriage and delivery, and supported the concepts of using monocytes macrophages as cellular vehicles to transport small molecular agents to the brain. PMID- 27001532 TI - Chemotherapy-induced nausea and vomiting is less controlled at delayed phase in patients with esophageal cancer: a prospective registration study by the CINV Study Group of Japan. AB - Chemotherapy is an indispensable therapeutic approach for esophageal cancer. Although chemotherapy-induced nausea and vomiting (CINV) is one of the most crucial adverse events, the current state of CINV in patients with esophageal cancer remains unclear. This multicenter prospective observational study analyzed data for 192 patents with esophageal cancer who underwent moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). The patients recorded their CINV incidence and severity daily for 7 days after receiving chemotherapy, using visual analog scales (VAS). Of the 192 patients, 181 received HEC including cisplatin, and 11 patients received MEC including nedaplatin. Approximately 81% of HEC and 82% of MEC patients received antiemetic therapy in compliance with guidelines. Although CINV was controlled relatively well in the early phase (days 1-4), it was not fully controlled in late phase (days 5-7) for both the HEC and MEC groups. Female sex was a major risk factor for delayed vomiting (P=0.034). Multivariate logistic regression analysis for VAS revealed that motion sickness, age, and use of other antiemetics were risk factors for delayed nausea. Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed CINV in both HEC and MEC patients. Identification of individual risk factors, such as female sex, will help develop personalized treatments for CINV. In the clinical setting for esophageal cancer, regimens that include nedaplatin might need to be treated as HEC. PMID- 27001533 TI - Determination of pseudocontact shifts of low-populated excited states by NMR chemical exchange saturation transfer. AB - Despite the critical roles of excited states in protein functions, they remain intractable for most structural studies because of their notably low populations. Chemical shifts for "invisible" states in slow exchange with the ground state are intuitively observed using nuclear magnetic resonance (NMR) chemical exchange saturation transfer (CEST) experiments. Here, we present a CEST NMR spectroscopy study for the observation of protein pseudocontact shifts (PCSs) of excited states, which carry valuable angular and distance information about these states. We first validate this approach, dubbed PCS-CEST, in the slow-exchange system of Abp1p SH3-Ark1p labeled with lanthanide ions, where the PCSs of the minor states resemble those of the holo-form ground state as expected. We further demonstrate that pre-existing folding transitional conformations of an FF domain exhibit remarkably lower PCS values than the ground state, which suggests that the low populated ensemble is unfolded or largely unfolded. A higher resolution of PCSs of the minor states is achieved using our 1D selective CEST experiments. Thus, PCS-CEST provides an exquisite structural probe into the minor but functionally essential excited states. PMID- 27001534 TI - Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning: A 5-Year Prospective Study. AB - PURPOSE: To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. DESIGN: Prospective study. PARTICIPANTS: A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for >=5 years. METHODS: Retinal nerve fiber layer imaging and VF testing were performed at ~4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (>=3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group. MAIN OUTCOME MEASURES: The HRs of VF progression. RESULTS: A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group. CONCLUSIONS: Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and its relevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment. PMID- 27001535 TI - Total Synthesis, Stereochemical Assignment, and Field-Testing of the Sex Pheromone of the Strepsipteran Xenos peckii. AB - The sex pheromone of the endoparasitoid insect Xenos peckii (Strepsiptera: Xenidae) was recently identified as (7E,11E)-3,5,9,11-tetramethyl-7,11 tridecadienal. Herein we report the asymmetric synthesis of three candidate stereostructures for this pheromone using a synthetic strategy that relies on an sp(3) -sp(2) Suzuki-Miyaura coupling to construct the correctly configured C7 alkene function. Comparison of (1) H NMR spectra derived from the candidate stereostructures to that of the natural sex pheromone indicated a relative configuration of (3R*,5S*,9R*). Chiral gas chromatographic (GC) analyses of these compounds supported an assignment of (3R,5S,9R) for the natural product. Furthermore, in a 16-replicate field experiment, traps baited with the synthetic (3R,5S,9R)-enantiomer alone or in combination with the (3S,5R,9S)-enantiomer captured 23 and 18 X. peckii males, respectively (mean+/-SE: 1.4+/-0.33 and 1.1+/ 0.39), whereas traps baited with the synthetic (3S,5R,9S)-enantiomer or a solvent control yielded no captures of males. These strong field trapping data, in combination with spectroscopic and chiral GC data, unambiguously demonstrate that (3R,5S,9R,7E,11E)-3,5,9,11-tetramethyl-7,11-tridecadienal is the X. peckii sex pheromone. PMID- 27001536 TI - Quality by Design Approaches to Formulation Robustness-An Antibody Case Study. AB - The International Conference on Harmonization Q8 (R2) includes a requirement that "Critical formulation attributes and process parameters are generally identified through an assessment of the extent to which their variation can impact the quality of the drug product," that is, the need to assess the robustness of a formulation. In this article, a quality-by-design-based definition of a "robust formulation" for a biopharmaceutical product is proposed and illustrated with a case study. A multivariate formulation robustness study was performed for a selected formulation of a monoclonal antibody to demonstrate acceptable quality at the target composition as well as at the edges of the allowable composition ranges and fulfillment of the end-of-shelf-life stability requirements of 36 months at the intended storage temperature (2 degrees C-8 degrees C). Extrapolation of 24 months' formulation robustness data to end of shelf life showed that the MAb formulation was robust within the claimed formulation composition ranges. Based on this case study, we propose that a formulation can be claimed as "robust" if all drug substance and drug product critical quality attributes remain within their respective end-of-shelf-life critical quality attribute-acceptance criteria throughout the entire claimed formulation composition range. PMID- 27001537 TI - Excreted Cytoplasmic Proteins Contribute to Pathogenicity in Staphylococcus aureus. AB - Excretion of cytoplasmic proteins in pro- and eukaryotes, also referred to as "nonclassical protein export," is a well-known phenomenon. However, comparatively little is known about the role of the excreted proteins in relation to pathogenicity. Here, the impact of two excreted glycolytic enzymes, aldolase (FbaA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), on pathogenicity was investigated in Staphylococcus aureus Both enzymes bound to certain host matrix proteins and enhanced adherence of the bacterial cells to host cells but caused a decrease in host cell invasion. FbaA and GAPDH also bound to the cell surfaces of staphylococcal cells by interaction with the major autolysin, Atl, that is involved in host cell internalization. Surprisingly, FbaA showed high cytotoxicity to both MonoMac 6 (MM6) and HaCaT cells, while GAPDH was cytotoxic only for MM6 cells. Finally, the contribution of external FbaA and GAPDH to S. aureus pathogenicity was confirmed in an insect infection model. PMID- 27001538 TI - Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization. AB - Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx. PMID- 27001539 TI - Staphylococcus aureus Phenol-Soluble Modulins Impair Interleukin Expression in Bovine Mammary Epithelial Cells. AB - The role of the recently described interleukin-32 (IL-32) in Staphylococcus aureus-induced mastitis, an inflammation of the mammary gland, is unclear. We determined expression of IL-32, IL-6, and IL-8 in S. aureus- and Escherichia coli infected bovine mammary gland epithelial cells. Using live bacteria, we found that in S. aureus-infected cells, induction of IL-6 and IL-8 expression was less pronounced than in E. coli-infected cells. Notably, IL-32 expression was decreased in S. aureus-infected cells, while it was increased in E. coli-infected cells. We identified the staphylococcal phenol-soluble modulin (PSM) peptides as key contributors to these effects, as IL-32, IL-6, and IL-8 expression by epithelial cells exposed to psm mutant strains was significantly increased compared to that in cells exposed to the isogenic S. aureus wild-type strain, indicating that PSMs inhibit the production of these interleukins. The use of genetically complemented strains confirmed this observation. Inasmuch as the decreased expression of IL-32, which is involved in dendritic cell maturation, impairs immune responses, our results support a PSM-dependent mechanism that allows for the development of chronic S. aureus-related mastitis. PMID- 27001540 TI - Displacement of Pathogens by an Engineered Bacterium Is a Multifactorial Process That Depends on Attachment Competition and Interspecific Antagonism. AB - Pathogen attachment to host cells is a key process during infection, and inhibition of pathogen adhesion is a promising approach to the prevention of infectious disease. We have previously shown that multivalent adhesion molecules (MAMs) are abundant in both pathogenic and commensal bacterial species, mediate early attachment to host cells, and can contribute to virulence. Here, we investigated the efficacy of an engineered bacterium expressing a commensal MAM on its surface in preventing pathogen attachment and pathogen-mediated cytotoxicity in a tissue culture infection model. We were able to dissect the individual contributions of adhesion and interspecific antagonism on the overall outcome of infection for a range of different pathogens by comparison with the results obtained with a fully synthetic adhesion inhibitor. We found that the potential of the engineered bacterium to outcompete the pathogen is not always solely dependent on its ability to hinder host attachment but, depending on the pathogenic species, may also include elements of interspecific antagonism, such as competition for nutrients and its ability to cause a loss of fitness due to production of antimicrobial factors. PMID- 27001542 TI - USE OF PATIENT ASSESSED HEALTH-RELATED QUALITY OF LIFE INSTRUMENTS IN PROSTATE CANCER RESEARCH: A SYSTEMATIC REVIEW OF THE LITERATURE 2002-15. AB - OBJECTIVES: The objectives of this study were to identify and qualitatively describe, in a systematic literature review, published studies that collected prostate cancer patients' health-related quality of life (HRQoL) estimates by using validated, generic instruments. METHODS: Systematic searches of the literature were made using the Medline, Cochrane Library, PsycINFO, and CINAHL electronic databases from 2002 to 2015. RESULTS: The search identified 2,171 references, of which 237 were obtained for full-text assessment; thirty-three of these articles were deemed relevant and included in the systematic review. An indirect valuation method was used in 73 percent (n = 24) of the studies. The most commonly used HRQoL instrument with an indirect valuation method was the EuroQol (EQ-5D; n = 21), and the second most common was the 15D (n = 5). A direct valuation method was used in 48 percent (n = 16) of the studies. Of these, the Visual Analogue Scale (VAS) was the most often used (n = 10), followed by the Time-Trade-Off (n = 6). HRQoL scores varied in localized and early stage disease between 0.63 and 0.91, and in advanced or metastatic disease stage between 0.50 and 0.87. There was also variance in the HRQoL instruments and study methods used, which explains the large variance in HRQoL scores between the various disease stages. CONCLUSIONS: Although utility and quality-adjusted life-years gained are considered important measures of effectiveness in health care, the number of studies in which utilities of prostate cancer patients have been estimated using generic HRQoL instruments, based on either direct or indirect measurement of HRQoL, is fairly small. PMID- 27001541 TI - N-Formyl-Perosamine Surface Homopolysaccharides Hinder the Recognition of Brucella abortus by Mouse Neutrophils. AB - Brucella abortus is an intracellular pathogen of monocytes, macrophages, dendritic cells, and placental trophoblasts. This bacterium causes a chronic disease in bovines and in humans. In these hosts, the bacterium also invades neutrophils; however, it fails to replicate and just resists the killing action of these leukocytes without inducing significant activation or neutrophilia. Moreover, B. abortus causes the premature cell death of human neutrophils. In the murine model, the bacterium is found within macrophages and dendritic cells at early times of infection but seldom in neutrophils. Based on this observation, we explored the interaction of mouse neutrophils with B. abortus In contrast to human, dog, and bovine neutrophils, naive mouse neutrophils fail to recognize smooth B. abortus bacteria at early stages of infection. Murine normal serum components do not opsonize smooth Brucella strains, and neutrophil phagocytosis is achieved only after the appearance of antibodies. Alternatively, mouse normal serum is capable of opsonizing rough Brucella mutants. Despite this, neutrophils still fail to kill Brucella, and the bacterium induces cell death of murine leukocytes. In addition, mouse serum does not opsonize Yersinia enterocolitica O:9, a bacterium displaying the same surface polysaccharide antigen as smooth B. abortus Therefore, the lack of murine serum opsonization and absence of murine neutrophil recognition are specific, and the molecules responsible for the Brucella camouflage are N-formyl-perosamine surface homopolysaccharides. Although the mouse is a valuable model for understanding the immunobiology of brucellosis, direct extrapolation from one animal system to another has to be undertaken with caution. PMID- 27001543 TI - Production of Quaternary alpha-Aminonitriles by Means of Indium-Catalyzed Three Component Reaction of Alkynes, Amines, and Trimethylsilyl Cyanide. AB - A novel synthesis of alpha-aminonitriles is described via an indium-catalyzed three-component coupling reaction of alkynes, amines, and trimethylsilyl cyanide (Me3SiCN). Hydroamination of alkynes with a subsequent nucleophilic addition of Me3SiCN resulted in a novel approach to quaternary alpha-aminonitrile derivatives. PMID- 27001545 TI - An automated microreactor for semi-continuous biosensor measurements. AB - Living bacteria or yeast cells are frequently used as bioreporters for the detection of specific chemical analytes or conditions of sample toxicity. In particular, bacteria or yeast equipped with synthetic gene circuitry that allows the production of a reliable non-cognate signal (e.g., fluorescent protein or bioluminescence) in response to a defined target make robust and flexible analytical platforms. We report here how bacterial cells expressing a fluorescence reporter ("bactosensors"), which are mostly used for batch sample analysis, can be deployed for automated semi-continuous target analysis in a single concise biochip. Escherichia coli-based bactosensor cells were continuously grown in a 13 or 50 nanoliter-volume reactor on a two-layered polydimethylsiloxane-on-glass microfluidic chip. Physiologically active cells were directed from the nl-reactor to a dedicated sample exposure area, where they were concentrated and reacted in 40 minutes with the target chemical by localized emission of the fluorescent reporter signal. We demonstrate the functioning of the bactosensor-chip by the automated detection of 50 MUgarsenite-As l(-1) in water on consecutive days and after a one-week constant operation. Best induction of the bactosensors of 6-9-fold to 50 MUg l(-1) was found at an apparent dilution rate of 0.12 h(-1) in the 50 nl microreactor. The bactosensor chip principle could be widely applicable to construct automated monitoring devices for a variety of targets in different environments. PMID- 27001546 TI - Sympathetic hyper-excitation in obesity and pulmonary hypertension: physiological relevance to the 'obesity paradox'. AB - BACKGROUND: Within the lung, sympathetic nerve activity (SNA) has an important role in facilitating pulmonary vasodilation. As SNA is elevated in obesity, we aimed to assess the impact of sympathetic hyper-excitation on pulmonary vascular homeostasis in obesity, and its potential role in ameliorating the severity of pulmonary hypertension (PH); the well-documented 'obesity paradox' phenomenon. METHODS: Zucker obese and lean rats were exposed to normoxia or chronic hypoxia (CH-10% O2) for 2 weeks. Subsequently, pulmonary SNA (pSNA) was recorded (electrophysiology), or the pulmonary microcirculation was visualized using Synchrotron microangiography. Acute hypoxic pulmonary vasoconstriction (HPV) was assessed before and after blockade of beta1-adrenergic receptors (ARs) (atenolol, 3 mg kg(-1)) and beta1+beta2-adrenergic (propranolol, 2 mg kg(-1)). RESULTS: pSNA of normoxic obese rats was higher than lean counterparts (2.4 and 0.5 MUV s, respectively). SNA was enhanced following the development of PH in lean rats, but more so in obese rats (1.7 and 6.8 MUV s, respectively). The magnitude of HPV was similar for all groups (for example, ~20% constriction of the 200-300 MUm vessels). Although beta-blockade did not modify HPV in lean rats, it significantly augmented the HPV in normoxic obese rats (beta1 and beta2 blockade), and more so in obese rats with PH (beta2-blockade alone). Western blots showed, while the expression of pulmonary beta1-ARs was similar for all rats, the expression of beta2-ARs was downregulated in obesity and PH. CONCLUSIONS: This study suggests that sympathetic hyper-excitation in obesity may have an important role in constraining the severity of PH and, thus, contribute in part to the 'obesity paradox' in PH. PMID- 27001547 TI - The utility of linked cancer registry and health administration data for describing system-wide outcomes and research: a BreastScreen example. AB - RATIONALE, AIMS AND OBJECTIVES: Stratification of women with screen-detected ductal carcinoma in situ (DCIS) by risk of subsequent invasive breast cancer (IBC) could assist treatment planning and selection of surveillance protocols that accord with risk. We assessed the utility of routinely collected administrative data for stratifying by IBC risk following DCIS detection in a population-based screening programme to inform ongoing surveillance protocols. METHODS: A retrospective cohort design was used, employing linked data from the South Australian breast screening programme and cancer registry. Women entered the study at screening commencement and were followed until IBC diagnosis, death or end of the study period (1 December 2010), whichever came first. Routinely collected administrative data were analyzed to identify predictors of invasive breast cancer. RESULTS: Proportional hazards regression confirmed that the DCIS cohort had an elevated risk of IBC after adjustment for relevant confounders (HR = 4.0 (95% CL 3.4, 4.8)), which accorded with previous study results. Within the DCIS cohort, conservative breast surgery and earlier year of screening commencement were both predictive of an elevated invasive breast cancer risk. CONCLUSIONS: These linked cancer registry and administrative data gave plausible estimates of IBC risk following DCIS diagnosis, but were limited in coverage of key items for further risk stratification. It is important that the research utility of administrative datasets is maximized in their design phase in collaboration with researchers. PMID- 27001544 TI - Targeting human oligodendrocyte progenitors for myelin repair. AB - Oligodendrocyte development has been studied for several decades, and has served as a model system for both neurodevelopmental and stem/progenitor cell biology. Until recently, the vast majority of studies have been conducted in lower species, especially those focused on rodent development and remyelination. In humans, the process of myelination requires the generation of vastly more myelinating glia, occurring over a period of years rather than weeks. Furthermore, as evidenced by the presence of chronic demyelination in a variety of human neurologic diseases, it appears likely that the mechanisms that regulate development and become dysfunctional in disease may be, in key ways, divergent across species. Improvements in isolation techniques, applied to primary human neural and oligodendrocyte progenitors from both fetal and adult brain, as well as advancements in the derivation of defined progenitors from human pluripotent stem cells, have begun to reveal the extent of both species-conserved signaling pathways and potential key differences at cellular and molecular levels. In this article, we will review the commonalities and differences in myelin development between rodents and man, describing the approaches used to study human oligodendrocyte differentiation and myelination, as well as heterogeneity within targetable progenitor pools, and discuss the advances made in determining which conserved pathways may be both modeled in rodents and translate into viable therapeutic strategies to promote myelin repair. PMID- 27001549 TI - Toxicological interactions of silver nanoparticles and organochlorine pesticides in mouse peritoneal macrophages. AB - Nanotechnology occupies a prominent space in economy and science due to the beneficial properties of nanomaterials. However, nanoparticles may pose risks to living organisms due to their adsorption and pro-oxidative properties. The aim of the current study was to investigate the effects of polymer-coated silver nanoparticles (AgNPs) and organochlorine pesticides (OCPs), as well as their combined effects on mouse peritoneal macrophages. Macrophages were isolated and exposed to three concentrations of AgNPs (groups: N1 = 30, N2 = 300 and N3 = 3000 ng.ml(-1)), two concentrations of OCPs (groups: P1 = 30 and P2 = 300 ng.ml(-1)) and the six possible combinations of these two contaminants for 24 h. AgNPs had irregular shape, Feret diameter of 8.7 +/- 7.5 nm and zeta potential of -28.7 +/- 3.9 mV in water and -10.7 +/- 1.04 mV in culture medium. OCP mixtures and the lower concentrations of AgNPs had no detectable effects on cell parameters, but the highest AgNPs concentration showed high toxicity (trypan blue and MTT assays) resulting in morphological changes, increase of nitric oxide levels and phagocytic index. Foremost, the association of N3 and P2 led to distinct effects from those observed under single exposure. PMID- 27001548 TI - Validation of PRISM (Pictorial Representation of Illness and Self Measure) as a novel visual assessment tool for the burden of suffering in tinnitus patients. AB - BACKGROUND: Chronic subjective tinnitus is a frequent condition that affects the subject's quality of life. The lack of objective measures of tinnitus necessitates the use of self-reporting and often time-consuming questionnaires for evaluating tinnitus severity. The Pictorial Representation of Illness and Self Measure (PRISM) is a two dimensional pictorial method to assess the burden of suffering. Patients illustrate their burden of suffering by the distance from a "self" to an illness circle, whereby a shorter distance indicates a higher burden of suffering. The aim of this prospective observational study was to validate the burden of suffering measured with PRISM in tinnitus patients by comparing it with different standardized questionnaires currently used in tinnitus evaluation. METHODS: A total of 188 patients filled out an online-based survey including sociodemographic variables and the following questionnaires: Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), WHO Quality of Life-Questionnaire (WHOQOL-BREF), and the Beck Depression Inventory (BDI). The subtle differences in the burden of suffering were accessed by using PRISM as an iPad version. Based on PRISM performance patients could easily be assigned in three groups, these being mildly, moderately, or severely affected akin to the standard questionnaires. RESULTS: The burden of suffering measured with PRISM correlated with the tinnitus severity (THI and TQ), depressive symptoms (BDI), and health related quality of life (WHOQOL-BREF) (all p <= 0.001). In the three PRISM groups tinnitus severity (THI and TQ), and depressive symptoms (BDI) differed significantly (all p <= 0.01). CONCLUSION: PRISM is an easily understood and time saving method for the assessment of burden of suffering in tinnitus patients. In daily clinical practice PRISM can help to identify patients with decompensated tinnitus that require more intensive treatment. PMID- 27001550 TI - Substrate specificity of proteolytic activity in the testes fluid and seminal plasma of the common carp Cyprinus carpio. AB - Substrate specificity in the seminal plasma and testes fluids of the common carp Cyprinus carpio was determined using gelatin, casein, albumin and haemoglobin. Proteolytic profiles of the testes and seminal plasma were compared. Different ranges of pH (5.5-9.5) and temperature (4-37 degrees C) were used during incubations of seminal plasma proteinases. Differences in proteolytic activity between testes and seminal plasma may reflect specific functions of the testes and sperm ducts in semen production. Seminal plasma metalloproteinases were characterized by higher substrate specificity than were serine proteinases. Zymography optimization for seminal plasma indicated that pH 7.5 and 22 degrees C were the optimal conditions for gel incubations. PMID- 27001551 TI - Factors associated with alcohol abuse and dependence among public transport workers in the metropolitan region of Belo Horizonte. AB - PURPOSE: Alcohol use may be associated with occupational factors. The objective of this study was to describe the prevalence and identify factors independently associated with alcohol abuse and dependence among urban public workers. METHODS: In this cross-sectional study, a proportional sample of 1607 bus drivers and conductors in three municipalities within the metropolitan region of Belo Horizonte was analyzed (total population: 17,740). Face-to-face interviews were conducted using a digital questionnaire that investigated working conditions and health. Affirmative responses to at least two questions in the CAGE questionnaire were considered to represent situations of abuse and dependence. The magnitude of the associations was estimated by means of logistic regression in univariable and multivariable models. RESULTS: The prevalence of alcohol abuse and dependence was 13.5 %. Positive associations with the following were identified: lower schooling level (incomplete high school: OR 1.77; 95 % CI 1.14-2.74; and elementary education: OR 1.57; 95 % CI 1.10-2.26); current smoking (OR 2.12; 95 % CI 1.47 3.07); non-participation in social activities (OR 1.74; 95 % CI 1.21-2.48); medical diagnosis of three of more diseases (OR 1.57; 95 % CI 1.01-2.42); aggression at work (OR 1.39; 95 % CI 1.01-1.93); and work-related distress (OR 1.85; 95 % CI 1.27-2.71). Workers who did not have children presented a lower chance of alcohol abuse and dependence than did those with children (OR 0.67; 95 % CI 0.45-0.99). CONCLUSIONS: Results of this study point that the urban public transport workers, users of public transport and also pedestrians could be on increased risk of accidents. So considering the importance of this service for all society and the risk involved in this activity, prospective studies are needed to clarify the relationships observed. PMID- 27001553 TI - Behaviour change communication in programmes to enhance infant and young child feeding: lessons from the field. PMID- 27001552 TI - HOLD study (Home care Obstructive Lung Disease): natural history of patients with advanced COPD. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth cause of death in western countries. Its final stage has clearly been forgotten by medical research in recent years. There exists consensus regarding the need to integrate palliative care in assisting these patients, but the difficulty in establishing a prognosis for the disease, establishing limits for life support measures, the lack of information about the disease's natural course and ignorance as to the most effective health-care structure for these patients' palliative treatment may be responsible for their late inclusion or non-inclusion in specific programmes. The main purpose of this work is to find out the natural background of patients with stage IV COPD and the main prognostic factors that influence these patients' survival. METHODS/DESIGN: Prospective observational study of a home patient cohort with stage IV COPD sent from Neumology consultations and Palliative Care Unit in La Paz Hospital in Madrid and Primary Care Health Centres in the area to the palliative care home support team. The goal is to study socio-demographic variables, prognosis, nutritional status, use of health resources, perceived quality of life, functionality, main symptomatology, use and effectiveness of opioids, adherence to treatment, prognostic information regarding the disease, information given by professionals, advance directives, social backup requirements and overburden level of the main caregiver. DISCUSSION: The HOLD study is a project aimed at finding out the prognostic factors and evolution of the disease COPD in its most advanced stage. The final goal is to improve the health and quality of life, in a personalised, integral way up to end of life and explore and foster communication with patients, as well as their participation and collaboration in decision-taking. The HOLD study can help us better understand what these patients' real palliative and care needs are, in order to more efficiently organise their treatment at end of life. PMID- 27001554 TI - The Role of Appearance in Adolescents' Experiences of Neurofibromatosis Type 1: A Survey of Young People and Parents. AB - Neurofibromatosis type 1 (NF1) is a genetic condition which can result in varying degrees of visible difference (disfigurement). Adolescence is a time when appearance concerns become more salient for many young people and is acknowledged as a particularly challenging time for individuals with NF1. There is currently little research into the psychosocial impact of the appearance changes associated with NF1 during this stage of life. In order to address this, surveys of young people with NF1 aged 14-24 years (n = 73), and parents of young people with NF1 (n = 55) were developed following interview studies with these groups. The surveys included the Perceived Stigma Questionnaire, Social Comfort Questionnaire, Body Esteem Scale (appearance subscale) and the Subjective Happiness Scale. Young people and parents identified appearance as central to young peoples' experience of NF1, however no significant difference was found on measures of body esteem, happiness, stigma or social comfort between those young people who reported their NF1 was noticeable to others and those who reported it was not. Findings from the parent survey indicated that their reports of greater perceived noticeability did relate to greater perceived stigma and lower levels of social comfort. Findings highlight the importance of attending to young people's concerns around appearance in general and managing the possibility of future appearance changes, rather than the current noticeability of NF1. PMID- 27001555 TI - Soil warming enhances the hidden shift of elemental stoichiometry by elevated CO2 in wheat. AB - Increase in atmospheric CO2 concentration ([CO2]) and associated soil warming along with global climate change are expected to have large impacts on grain mineral nutrition in wheat. The effects of CO2 elevation (700 MUmol l(-1)) and soil warming (+2.4 degrees C) on K, Ca and Mg concentrations in the xylem sap and their partitioning in different organs of wheat plant during grain filling were investigated. Results showed that the combination of elevated [CO2] and soil warming improved wheat grain yield, but decreased plant K, Ca and Mg accumulation and their concentrations in the leaves, stems, roots and grains. The reduced grain mineral concentration was attributed to the lowered mineral uptake as exemplified by both the decreased stomatal conductance and mineral concentration in the xylem sap. These findings suggest that future higher atmospheric [CO2] and warmer soil conditions may decrease the dietary availability of minerals from wheat crops. Breeding wheat cultivars possessing higher ability of mineral uptake at reduced xylem flux in exposure to climate change should be a target. PMID- 27001556 TI - Synthesis of high molecular weight polyethylene using iminopyridyl nickel catalysts. AB - A series of iminopyridyl Ni(ii) catalysts containing both the dibenzhydryl and the naphthyl moieties can polymerize ethylene with high activity and high thermal stability, generating polyethylene with a molecular weight of up to one million. In alpha-olefin polymerization, semicrystalline polymers with high melting temperatures are generated. PMID- 27001557 TI - Post-transcriptional regulation of gene expression in neural stem cells. AB - Expression of each gene can be controlled at several steps during the flow of genetic information from DNA to protein. Tight regulation of gene expression is especially important for stem cells because of their greater ripple effects, compared with terminally differentiated cells. Dysregulation of gene expression arising in stem cells can be perpetuated within the stem cell pool via self renewal throughout life. In addition, transcript profiles within stem cells can determine the selective advantage or disadvantage of each cell, leading to changes in cell fate, such as a tendency for proliferation, death, and differentiation. The identification of neural stem/progenitor cells (NSPCs) and greater understanding of their cellular physiology have raised the possibility of using NSPCs to replace damaged or injured neurons. However, an accurate grasp of gene expression control must take precedence in order to use NSPCs in therapies for neurological diseases. Recently, accumulating evidence has demonstrated the importance of post-transcriptional regulation in NSPC fate decisions. In this review, we will summarize and discuss the recent findings on key mRNA modulators and their vital roles in NSPC homeostasis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001558 TI - Major inter-personal variation in the increase and maximal level of 25-hydroxy vitamin D induced by UVB. AB - Vitamin D influences skeletal health as well as other aspects of human health. Even when the most obvious sources of variation such as solar UVB exposure, latitude, season, clothing habits, skin pigmentation and ethnicity are selected for, variation in the serum 25-hydroxy vitamin D (25(OH)D) response to UVB remains extensive and unexplained. Our study assessed the inter-personal variation in 25(OH)D response to UVR and the maximal obtainable 25(OH)D level in 22 healthy participants (220 samples) with similar skin pigmentation during winter with negligible ambient UVB. Participants received identical UVB doses on identical body areas until a maximal level of 25(OH)D was reached. Major inter personal variation in both the maximal obtainable UVB-induced 25(OH)D level (range 85-216 nmol l(-1), mean 134 nmol l(-1)) and the total increase in 25(OH)D (range 3-139 nmol l(-1), mean 48 nmol l(-1)) was found. A linear model including measured 25(OH)D baselines as personal intercepts explained 54.9% of the variation. By further including personal slopes in the model, as much as 90.8% of the variation could be explained. The explained variation constituted by personal differences in slopes thus represented 35.9%. Age, vitamin D receptor gene polymorphisms, height and constitutive skin pigmentation (a skin area not exposed to UVB) explained 15.1% of this variation. Despite elimination of most known external sources of variation, our study demonstrated inter-personal variation corresponding to an observed maximal difference of 136 nmol l(-1) in the total increase of 25(OH)D and 131 nmol l(-1) in the maximal level of 25(OH)D. PMID- 27001559 TI - Social anhedonia and gamma band abnormalities as a composite/multivariate endophenotype for schizophrenia: a dense array EEG study. AB - AIM: Social anhedonia and gamma band oscillations are proposed as a promising endophenotype for schizophrenia (SZ). The aim was to assess whether social anhedonia and spontaneous gamma band oscillations could be used as multivariate/composite endophenotypic measures for SZ. METHODS: Sixty consented subjects, of which 20 remitted SZ patients, 20 unaffected siblings of patients with schizophrenia (US) and 20 healthy controls (HC) were recruited for the study. The Revised Social Anhedonia Scale, Temporal Experience of Pleasure Scale and the Schizotypal Personality Questionnaire assessed social anhedonia, temporal experience of pleasure and schizotypal features. All participants underwent awake, resting state 192-channel dense array electroencephalographic recording. Gamma spectral power and coherence were calculated. We performed chi-square test, one-way analysis of variance, Pearsons correlation coefficient and step-by-step linear discriminant functional analysis. RESULTS: Social anhedonia was significantly higher and anticipatory aspects of pleasure were significantly lower in both SZ and US compared with HC. US scored significantly higher than HC in the Schizotypal Personality Questionnaire. Spectral power of high gamma band (>70 Hz) was significantly lower over the right temporo-parietal and midline regions in both SZ and US than HC. We accurately classified (85%) three groups when social anhedonia, high gamma band spectral power of midline, right frontal and right fronto-temporal interhemispheric gamma coherence were considered as composite measures rather than each variable representing independently. CONCLUSION: We propose region-specific high gamma spectral 'power and coherence' and social anhedonia as composite/multivariate measures could be a useful measure in distinguishing schizophrenia patients and unaffected siblings from healthy controls. PMID- 27001560 TI - Effect of bed exercises and gum chewing on abdominal sounds, flatulence and early discharge in the early period after caesarean section. AB - AIMS AND OBJECTIVES: The purpose of this study was to determine the effects of bed exercises and gum chewing on abdominal sounds, flatulence and early discharge on women who have given birth at the Cengiz Gokcek Gynecology and Obstetrics Hospital surgery services in Gaziantep city centre. BACKGROUND: Caesarean operation is the most significant surgical intervention that affects central nervous system and decelerates bowel movements in the postoperative period. Conducted studies show that practices such as gum chewing ensure that bowel functions start in a short time through early feeding and mobilisation and shorten the duration of hospital stay. DESIGN: A randomised controlled experimental was used. METHOD: A total of 120 women participated in the study in three groups of 40 for gum, exercise and control groups. Gum was given to the groups in the gum section two hours after the ceasarean, the women chewed gum for the first eight hours until flatulence for 15 minutes every two hours. However, the women in the exercise group started moving two hours after the caesarean for the first eight hours until flatulence for five minutes every two hours. The control group consisted of women under routine treatment and care of the hospital. All women were hourly evaluated in terms of abdominal sounds, flatulence and defaecation. RESULTS: It was determined that following caesarean, bowel functions started in three groups at the same time, there was no significant difference between three groups. It was determined that the gum group, exercise group and the control group were discharged earlier, there was no significant difference between three groups CONCLUSION: The study results show that spinal anaesthesia have positive effects on discharge time after caesarean section operation. RELEVANCE TO CLINICAL PRACTICE: This study provides useful information to clinician and researchers when determining practices such as postoperative standing up in early period, gum chewing and early liquid intake related to postoperative bowel functions after abdominal operations. PMID- 27001561 TI - Deep anesthesia worsens outcome of rats with inflammatory responses. AB - OBJECTIVE: We tested the hypothesis that deep anesthesia with sevoflurane, known as a potent immunomodulator, for 4 h would worsen the 24-h outcomes of rats through modulation of the inflammatory responses. METHODS: Forty-nine male Wistar rats, administered low dose of lipopolysaccharide (0.5 mg/kg) intravenously to elicit moderate inflammatory responses mimicked mild surgical stress, underwent one minimum alveolar concentration (MAC) or 2 MAC sevoflurane anesthesia for 4 h. The 24-h survival rate, arterial blood gases, plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha concentrations, and rate of T lymphocyte apoptosis in spleen were evaluated. We further examined the effects of hypotension and TNF alpha discharge on the survival rate. RESULTS: The survival rate in 2 MAC group was significantly lower accompanied with decreased base excess and increased level of cytokines (IL-6, TNF-alpha) compared to 1 MAC group. The apoptosis rate did not differ between the two groups. Neither norepinephrine infusion to restore hypotension nor administration of anti-TNF-alpha antibody improved the outcome in the 2 MAC group. CONCLUSIONS: Deep anesthesia with sevoflurane even for a short term period augments the release of inflammatory cytokines evoked by inflammatory insults like surgical stress, impairs the acid-base balance, and subsequently deteriorates the outcomes. PMID- 27001562 TI - Water in Ionic Liquids: Correlation between Anion Hydrophilicity and Near Infrared Fingerprints. AB - We show that fingerprints of the different states of water association can be clearly distinguished in the range of the first overtone of water's symmetric O-H stretching in the spectra of water-saturated [EMIm](+) -based ionic liquids with anions of substantially different hydrophilicity, such as hydrophobic [(CF3 SO2 )2 N](-) , moderately hydrophilic [CF3 SO3 ](-) , and highly hydrophilic [HSO4 ]( ) . PMID- 27001564 TI - Definition of First-Line Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer. PMID- 27001563 TI - 21-Gene Recurrence Score Assay As a Predictor of Adjuvant Chemotherapy Administration for Early-Stage Breast Cancer: An Analysis of Use, Therapeutic Implications, and Disparity Profile. AB - PURPOSE: The 21-gene Recurrence Score (RS) assay is used to predict disease recurrence and benefit of chemotherapy in estrogen receptor-positive, lymph node negative early-stage breast cancer (EBC). Our study is the first analysis of trends and differences in the use of the RS assay and its impact on recommending chemotherapy in a population-based data set. METHODS: Patients with EBC diagnosed from 2004 to 2012 and included in the National Cancer Data Base were analyzed. Multivariate logistic regression analysis was used to estimate the covariates associated with use of the test and its impact on chemotherapy decisions. RESULTS: The RS assay was ordered for 54.0% of the 143,032 identified patients. Of all the variables, RS assay had the strongest association with recommendation for chemotherapy, with an adjusted odds ratio (AOR) of 83 for high assay scores. When indicated, test use was significantly associated with younger age, white race, academic centers, private insurance, and pT2/pN0(i+) grade 2 to 3 disease. Black patients (AOR, 1.31; 95% CI, 1.20 to 1.43) and those treated in community facilities (AOR, 1.49; 95% CI, 1.35 to 1.63) were more likely to be tested outside the National Comprehensive Cancer Network guidelines. Black patients (AOR, 1.51; 95% CI, 1.31 to 1.69) and those with high tumor grade (AOR, 30.76; 95% CI, 26.48 to 35.73) had significantly higher assay scores. Younger black patients (AOR, 1.33; 95% CI, 1.16 to 1.54) were more likely to receive chemotherapy despite low assay scores. CONCLUSION: The RS assay significantly influences clinicians' recommendations for chemotherapy in patients with EBC. Black patients tended to have higher assay scores, which may reflect use patterns or less favorable tumor biology for estrogen receptor-positive disease. There are significant differences in use and clinical implications of the test on the basis of race, insurance, and type of facility. PMID- 27001565 TI - Association of Vitamin D Levels With Outcome in Patients With Melanoma After Adjustment For C-Reactive Protein. AB - PURPOSE: To evaluate for an association between 25-hydroxyvitamin D levels (vitamin D) and outcome measures in patients with melanoma after evaluation is controlled for systemic inflammatory response (SIR) on the basis of simultaneous C-reactive protein (CRP) measurement. MATERIALS AND METHODS: Plasma samples from 1,042 prospectively observed patients with melanoma were assayed for vitamin D and CRP. The associations of demographics and CRP with vitamin D were determined, followed by a determination of the association between vitamin D and stage and outcome measures from the date of blood draw. The vitamin D level was considered sufficient if it was 30 to 100 ng/mL. Kaplan-Meier and Cox regression analyses were performed. RESULTS: The median vitamin D level was 25.0 ng/mL. The median follow-up time was 7.1 years. A lower vitamin D was associated with the blood draw during fall/winter months (P < .001), older age (P = .001), increased CRP (P < .001), increased tumor thickness (P < .001), ulcerated tumor (P = .0105), and advanced melanoma stage (P = .0024). On univariate analysis, lower vitamin D was associated with poorer overall (OS; P < .001), melanoma-specific survival (MSS; P = .0025), and disease-free survival (DFS; P = .0466). The effect of vitamin D on these outcome measures persisted after adjustment for CRP and other covariates. Multivariable hazards ratios per unit decrease of vitamin D were 1.02 for OS (95% CI, 1.01 to 1.04; P = .0051), 1.02 for MSS (95% CI, 1.00 to 1.04; P = .048), and 1.02 for DFS (95% CI, 1.00 to 1.04; P = .0427). CONCLUSION: Lower vitamin D levels in patients with melanoma were associated with poorer outcomes. Although lower vitamin D was strongly associated with higher CRP, the associations of lower vitamin D with poorer OS, MSS, and DFS were independent of this association. Investigation of mechanisms responsible for these associations may be of value to patients with melanoma. PMID- 27001566 TI - Therapy for Secondary CNS Involvement in Malignant Lymphomas: No Standard Yet! PMID- 27001567 TI - Reply to A. Korfel et al. PMID- 27001568 TI - A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse. AB - PURPOSE: Farletuzumab is a humanized monoclonal antibody that binds to folate receptor-alpha, which is highly expressed in ovarian carcinoma and largely absent from normal tissue. Farletuzumab was investigated in a double-blind, randomized phase III study in platinum-sensitive ovarian cancer. PATIENTS AND METHODS: Eligible patients had first recurrent ovarian cancer 6-24 months following completion of platinum-taxane chemotherapy. All patients received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomly assigned test products in a 1:1:1 ratio: farletuzumab 1.25 mg/kg, farletuzumab 2.5 mg/kg, or placebo). The single-agent test product was continued weekly until disease progression. The primary end point was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors. Additional analyses not outlined in the original protocol were prespecified in the final statistical analysis plan, including a subgroup analysis by baseline CA-125 and farletuzumab exposure levels. RESULTS: A total of 1,100 women were randomly assigned to treatment dose or placebo. PFS from the primary analysis was 9.0, 9.5, and 9.7 months for the placebo, farletuzumab 1.25 mg/kg, and farletuzumab 2.5 mg/kg groups, respectively. Neither farletuzumab group was statistically different from the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.81 to 1.21] and 0.86 [95% CI, 0.70 to 1.06] for farletuzumab 1.25 mg/kg and 2.5 mg/kg group v placebo, respectively). In the prespecified subgroup, baseline CA-125 levels not more than three times the upper limit of normal (ULN) correlated with longer PFS (HR, 0.49; P = .0028) and overall survival (OS) (HR, 0.44; P = .0108) for farletuzumab 2.5 mg/kg versus placebo. Subgroup analysis of farletuzumab exposure above the median, regardless of dose, showed significantly better PFS versus placebo. The most common adverse events were those associated with chemotherapy. CONCLUSION: Neither farletuzumab dose met the study's primary PFS end point. Prespecified subgroup analyses demonstrated that patients with CA-125 levels not more than three times the ULN and patients with higher farletuzumab exposure showed superior PFS and OS compared with placebo. PMID- 27001569 TI - Racial/Ethnic Differences in Adverse Outcomes Among Childhood Cancer Survivors: The Childhood Cancer Survivor Study. AB - PURPOSE: Childhood cancer survivors carry a high burden of treatment-related morbidity; however, race/ethnicity-specific risks of adverse outcomes are not well understood. METHODS: Data from the Childhood Cancer Survivor Study, a cohort of survivors of at least 5 years, were used to compare Hispanic (n = 750, 5.4%) and non-Hispanic black (NHB: n = 694, 5.0%) survivors to non-Hispanic white patients (NHW: n = 12,397, 89.6%) for late mortality, subsequent neoplasms, and chronic health conditions. RESULTS: NHBs and Hispanics reported lower socioeconomic status (SES) and higher prevalence of obesity, and NHBs reported higher prevalence of hypertension. NHBs had higher rate of all-cause mortality (relative rate [RR], 1.4; 95% CI, 1.1 to 1.9; P = .008), which was abrogated (RR, 1.0; 95% CI, 0.8 to 1.4; P = .9) after adjusting for SES. Nonmelanoma skin cancer was not observed among irradiated NHBs, and the risk was lower among Hispanic survivors (RR, 0.3; 95% CI, 0.1 to 0.7) compared with NHWs. Both NHBs and Hispanics demonstrated elevated risks for diabetes; these risks persisted after adjusting for SES and obesity (NHBs: RR, 2.8; 95% CI, 1.1 to 6.7; Hispanics: RR, 3.1; 95% CI, 1.5 to 6.4). NHBs were more likely to report cardiac conditions (RR, 1.8; 95% CI, 1.1 to 2.7), but the risk was attenuated after adjusting for cardiovascular risk factors. Therapeutic exposures did not affect racial/ethnic differences in mortality (all cause or cause specific), chronic health conditions, or subsequent neoplasms. CONCLUSION: By and large, NHB and Hispanic childhood cancer survivors experience a comparable burden of morbidity and mortality to their NHW counterparts. The few differences in risk were explained by the racial/ethnic differences in socioeconomic status and/or cardiovascular risk factors. PMID- 27001571 TI - A Plethora of Therapeutic Opportunities for Elderly Patients With Cancer: A Nontrivial Choice. PMID- 27001570 TI - Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. AB - PURPOSE: Recurrent glioblastoma multiforme (GBM) is incurable with current therapies. Biallelic mismatch repair deficiency (bMMRD) is a highly penetrant childhood cancer syndrome often resulting in GBM characterized by a high mutational burden. Evidence suggests that high mutation and neoantigen loads are associated with response to immune checkpoint inhibition. PATIENTS AND METHODS: We performed exome sequencing and neoantigen prediction on 37 bMMRD cancers and compared them with childhood and adult brain neoplasms. Neoantigen prediction bMMRD GBM was compared with responsive adult cancers from multiple tissues. Two siblings with recurrent multifocal bMMRD GBM were treated with the immune checkpoint inhibitor nivolumab. RESULTS: All malignant tumors (n = 32) were hypermutant. Although bMMRD brain tumors had the highest mutational load because of secondary polymerase mutations (mean, 17,740 +/- standard deviation, 7,703), all other high-grade tumors were hypermutant (mean, 1,589 +/- standard deviation, 1,043), similar to other cancers that responded favorably to immune checkpoint inhibitors. bMMRD GBM had a significantly higher mutational load than sporadic pediatric and adult gliomas and all other brain tumors (P < .001). bMMRD GBM harbored mean neoantigen loads seven to 16 times higher than those in immunoresponsive melanomas, lung cancers, or microsatellite-unstable GI cancers (P < .001). On the basis of these preclinical data, we treated two bMMRD siblings with recurrent multifocal GBM with the anti-programmed death-1 inhibitor nivolumab, which resulted in clinically significant responses and a profound radiologic response. CONCLUSION: This report of initial and durable responses of recurrent GBM to immune checkpoint inhibition may have implications for GBM in general and other hypermutant cancers arising from primary (genetic predisposition) or secondary MMRD. PMID- 27001572 TI - Modifiable Factors Associated With Aging Phenotypes Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia. AB - PURPOSE: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for low bone mineral density (BMD) and frail health, outcomes potentially modifiable by altering health behaviors and/or treating endocrine abnormalities. We evaluated associations between lifestyle and hormonal deficits with risk of low BMD and frailty among survivors of ALL. PATIENTS AND METHODS: Participants included 862 survivors of ALL (median age, 31.3 years [range, 18.4 to 59.7 years]) enrolled in the St Jude Lifetime Cohort study. Bone density was measured using quantitative computed tomography of L1 through L2 vertebrae; low BMD was defined as an age- and sex-standardized z score < -1. The presence of frailty or prefrailty was defined as having at least two of the following: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Hormonal deficiencies were determined according to medical history, medications, and laboratory findings (insulin-like growth factor 1, follicle stimulating hormone, luteinizing hormone, and testosterone levels). Logistic regression was used to examine associations between lifestyle (smoking, alcohol consumption, and activity levels) and deficiencies in growth hormone (GHD) and/or sex steroids with low BMD and frailty. RESULTS: Thirty percent of survivors met criteria for low BMD, and 18.6% for frailty/prefrailty. After adjusting for body mass index, low BMD was associated with GHD (odds ratio [OR], 1.59; 95% CI, 1.02 to 2.13) and current smoking (OR, 1.71; 95% CI, 1.02 to 2.85) among men; and GHD (OR, 2.18; 95% CI, 1.26 to 3.78) and moderate alcohol consumption (OR, 2.09; 95% CI, 1.14 to 3.83) among women. After adjusting for current age, the odds of frailty/prefrailty were increased among men with GHD (OR, 2.97; 95% CI, 1.56 to 5.67) and those who smoked (OR, 3.26; 95% CI, 1.65 to 6.43); there were no significant associations among women. CONCLUSION: The findings suggest that survivors of ALL should receive counseling regarding lifestyle and undergo screening for hormonal deficits to minimize the risk of low BMD and frailty. PMID- 27001573 TI - [18F]Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) in Suspected Recurrent Breast Cancer: A Prospective Comparative Study of Dual-Time-Point FDG-PET/CT, Contrast-Enhanced CT, and Bone Scintigraphy. AB - PURPOSE: To prospectively investigate the diagnostic accuracy of [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with dual-time-point imaging, contrast-enhanced CT (ceCT), and bone scintigraphy (BS) in patients with suspected breast cancer recurrence. PATIENTS AND METHODS: One hundred women with suspected recurrence of breast cancer underwent 1-hour and 3-hour FDG-PET/CT, ceCT, and BS within approximately 10 days. The study was powered to estimate the precision of the individual imaging tests. Images were visually interpreted using a four-point assessment scale, and readers were blinded to other test results. The reference standard was biopsy along with treatment decisions and clinical follow-up (median, 17 months). RESULTS: FDG-PET/CT resulted in no false negatives and fewer false positives than the other imaging techniques. Accuracy of results were similar for 1-hour and 3 hour FDG-PET/CT. For distant recurrence, the area under the receiver operating curve was 0.99 (95% CI, 0.97 to 1) for FDG-PET/CT, 0.84 (95% CI, 0.73 to 0.94) for ceCT, and 0.86 (95% CI, 0.77 to 0.94) for the combined ceCT+BS. Of 100 patients, 22 (22%) were verified with distant recurrence, and 18 of these had bone involvement. Nineteen patients (19%) had local recurrence only. In exploratory analyses, diagnostic accuracy of FDG-PET/CT was better than ceCT alone or ceCT combined with BS in diagnosing distant, bone, and local recurrence, shown by a greater area under the receiver operating curve and higher sensitivity, specificity, and superior likelihood ratios. CONCLUSION: FDG-PET/CT was accurate in diagnosing recurrence in breast cancer patients. It allowed for distant recurrence to be correctly ruled out and resulted in only a small number of false-positive cases. Exploratory findings suggest that FDG-PET/CT has greater accuracy than conventional imaging technologies in this patient group. PMID- 27001574 TI - Reply to A. Fiorentino et al. PMID- 27001575 TI - Reply to A. Korfel et al. PMID- 27001576 TI - Reply to T. Reinert et al. PMID- 27001577 TI - On Adjuvant Hormone Therapy in Epithelial Ovarian Cancer. PMID- 27001578 TI - Reply to C. Shah et al. PMID- 27001579 TI - Radiation Therapy and the Evolving Definition of Low Risk in Ductal Carcinoma in Situ. PMID- 27001580 TI - US Food and Drug Administration and Representation of Older Adults in Clinical Trials. PMID- 27001581 TI - Better Evidence About Older Adults With Cancer Will Not Improve Survival Rates Alone; Clinicians Need More Support. PMID- 27001582 TI - Reply to S. Kilickap et al, Y. Karakas et al, and I.A. Voutsadakis. PMID- 27001583 TI - Reply to N. Lowy et al and to J. Dhanda et al. PMID- 27001584 TI - Does Adjuvant Hormone Therapy Improve Survival in Epithelial Ovarian Cancer? PMID- 27001585 TI - Analysis of the Adjuvant Hormone Therapy Randomized Trial. PMID- 27001586 TI - Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations. AB - PURPOSE: An American Society of Clinical Oncology (ASCO) panel considered the Cancer Care Ontario (CCO) recommendations on the role of patient and disease factors in selecting adjuvant therapy for women with early-stage breast cancer for endorsement. METHODS: ASCO staff reviewed the CCO guideline for methodologic rigor, and an ASCO panel of content experts reviewed the content of the recommendations. CCO RECOMMENDATIONS: For making decisions regarding adjuvant therapy, nodal status, tumor size, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, and lymphovascular invasion are relevant; Oncotype DX score and Adjuvant! Online may be used as risk stratification tools; and age, menopausal status, and medical comorbidities should be considered. Chemotherapy should be considered for patients with positive lymph nodes, ER-negative disease, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node-negative tumors (T > 5 mm), triple-negative (ER-negative, PgR-negative, HER2-negative) tumors, lymphovascular invasion positivity, or estimated distant relapse risk of greater than 15% at 10 years based on Oncotype DX recurrence score (RS). Chemotherapy may not be beneficial or required for small node-negative tumors (T < 5 mm) without high-risk features or for patients with HER2-negative, strongly ER-positive, and PgR-positive cancer with micrometastatic nodal disease, T less than 5 mm, or Oncotype DX RS with an estimated distant relapse risk of less than 15% at 10 years. ASCO PANEL CONCLUSION: The ASCO panel endorses the recommendations with minor suggested revisions and highlights three areas that warrant further consideration: tumor histology and adjuvant therapy recommendations, risk stratification tools and proposed Oncotype DX RS thresholds to guide decisions about chemotherapy, and patient factors in decision making. PMID- 27001587 TI - Incorporating Androgen Deprivation With Dose-Escalated External-Beam Radiotherapy for Prostate Cancer. AB - The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.A 71-year-old man was seen by his primary care physician for routine evaluation in early 2015. On digital rectal examination, his prostate was moderately enlarged, although he had no obvious areas of palpable disease. His prostate-specific antigen (PSA) level was 7.1 ng/mL. A standard ultrasound-guided biopsy of his prostate revealed a 60-mL prostate volume and a single core (out of 12) of Gleason 3 + 3 disease. He chose to undergo surveillance. Six months later, his PSA level had risen to 10.0 ng/mL; there was still no palpable disease on digital rectal examination. Multiparametric magnetic resonance imaging of his prostate and pelvis revealed two suspicious intraprostatic lesions with restricted diffusion, focal and earlier enhancement with contrast than adjacent normal prostate, and hypointense features on T2-weighted imaging; these findings were highly suspicious for high grade prostate cancer (Fig 1). Magnetic resonance imaging-ultrasound fusion targeted biopsy of each lesion yielded a total of four positive biopsy cores of Gleason 4 + 3 = 7, involving 50% to 80% of each core, with perineural invasion noted. The patient's medical history is notable for overweight (but not morbidly obese), hypercholesterolemia, hypertension, cataract surgeries, and inguinal hernia repair, but the patient is otherwise healthy. He has decided against prostatectomy and brachytherapy because of strong personal preference. In particular, he wanted to avoid anesthesia, and was concerned about the potential for greater urinary incontinence and/or urinary irritation associated with these treatments compared with external-beam radiotherapy (RT).(1,2). PMID- 27001588 TI - Antiangiogenic Therapy for Glioblastoma: Complex Biology and Complicated Results. PMID- 27001589 TI - Window-of-Opportunity Trials in the Preoperative Setting: Insights Into Drug Development for Estrogen Receptor-Positive Breast Cancer. PMID- 27001591 TI - Optimizing Treatment Risk and Benefit for Elderly Patients With Advanced Non Small-Cell Lung Cancer: The Right Treatment for the Right Patient. AB - The Oncology Grand Rounds series is designed to place original reports published in theJournal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published inJournal of Clinical Oncology, to patients seen in their own clinical practice.A 78-year-old woman with a 40-pack year smoking history has been referred for treatment of advanced non-small-cell lung cancer. She presented with a persistent cough and worsening dyspnea on exertion. A chest x-ray followed by a chest computed tomography scan revealed a 3 cm right upper lobe mass along with a moderate-size pleural effusion. Pleural fluid cytology was positive for adenocarcinoma. A brain magnetic resonance imaging scan was negative. A reflex molecular profile, includingKRAS,EGFR,ALK,BRAF,HER2,RET,MET, andROS, did not reveal an actionable abnormality. Her past medical history includes diabetes, hypertension, and osteopenia. Her medications include a beta-blocker, angiotensin-converting enzyme inhibitor, oral antidiabetic agent, calcium, and vitamin D. The laboratory evaluation is notable for a hemoglobin of 10.8 g/dL and a creatinine clearance of 36 mL/min. The other laboratories are within normal limits. She is somewhat limited by the shortness of breath but maintains an Eastern Cooperative Oncology Group performance status of 1. She is independent in all of her instrumental and basic activities of daily living and denies falls. She has been referred to discuss treatment options. PMID- 27001592 TI - What Is the Malignancy Risk in Neurofibromatosis Type 1? PMID- 27001590 TI - Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013. AB - PURPOSE: The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013. PATIENTS AND METHODS: TBCRC 013 was a multicenter prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. From July 2009 to April 2012, 127 patients from 14 sites were enrolled; 109 (86%) patients had pretreatment primary tumor samples suitable for 21-gene RS analysis. Clinical variables, time to first progression (TTP), and 2-year overall survival (OS) were correlated with the 21-gene RS by using log-rank, Kaplan-Meier, and Cox regression. RESULTS: Median patient age was 52 years (21 to 79 years); the majority had hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (72 [66%]) or hormone receptor-positive/HER2-positive (20 [18%]) breast cancer. At a median follow-up of 29 months, median TTP was 20 months (95% CI, 16 to 26 months), and median survival was 49 months (95% CI, 40 months to not reached). An RS was generated for 101 (93%) primary tumor samples: 22 (23%) low risk (< 18), 29 (28%) intermediate risk (18 to 30); and 50 (49%) high risk (>= 31). For all patients, RS was associated with TTP (P = .01) and 2-year OS (P = .04). In multivariable Cox regression models among 69 patients with estrogen receptor (ER)-positive/HER2-negative cancer, RS was independently prognostic for TTP (hazard ratio, 1.40; 95% CI, 1.05 to 1.86; P = .02) and 2-year OS (hazard ratio, 1.83; 95% CI, 1.14 to 2.95; P = .013). CONCLUSION: The 21-gene RS is independently prognostic for both TTP and 2-year OS in ER-positive/HER2-negative de novo stage IV breast cancer. Prospective validation is needed to determine the potential role for this assay in the clinical management of this patient subset. PMID- 27001593 TI - Guideline on Muscle-Invasive and Metastatic Bladder Cancer (European Association of Urology Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement. AB - PURPOSE: To endorse the European Association of Urology guideline on muscle invasive (MIBC) and metastatic bladder cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS: The guideline on MIBC and metastatic bladder cancer was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and recommendations. RESULTS: The ASCO Endorsement Panel determined that the recommendations from the European Association of Urology guideline on MIBC and metastatic bladder cancer, published online in March 2015, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorses the guideline on MIBC and metastatic bladder cancer and has added qualifying statements, including highlighting the use of chemoradiotherapy for select patients with MIBC and recommending a preference for clinical trials in the treatment of metastatic disease in the second-line setting. RECOMMENDATIONS: Multidisciplinary care for patients with MIBC and metastatic bladder cancer is critical. The standard treatment of MIBC (cT2-T4a N0M0) is neoadjuvant cisplatin based combination chemotherapy followed by radical cystectomy. In cisplatin ineligible patients, radical cystectomy alone is recommended. Adjuvant cisplatin based chemotherapy may be offered to high-risk patients who have not received neoadjuvant therapy. Chemoradiotherapy may be offered as an alternative to cystectomy in appropriately selected patients with MIBC and in some patients for whom cystectomy is not an option. Metastatic disease should be treated with cisplatin-containing combination chemotherapy or with carboplatin combination chemotherapy or single agents in patients ineligible for cisplatin.Additional information is available at http://www.asco.org/endorsements/MIBC and www.asco.org/guidelineswiki. PMID- 27001594 TI - Conserved motif VIII of murine DNA methyltransferase Dnmt3a is essential for methylation activity. AB - BACKGROUND: Dnmt3a is a DNA methyltransferase that establishes de novo DNA methylation in mammals. The structure of the Dnmt3a C-terminal domain is similar to the bacterial M. HhaI enzyme, a well-studied prokaryotic DNA methyltransferase. No X-ray structure is available for the complex of Dnmt3a with DNA and the mechanistic details of DNA recognition and catalysis by mammalian Dnmts are not completely understood. RESULTS: Mutant variants of the catalytic domain of the murine Dnmt3a carrying substitutions of highly conserved N167, R200, and R202 have been generated by site directed mutagenesis and purified. Their methylation activity, DNA binding affinity, ability to flip the target cytosine out of the DNA double helix and covalent complex formation with DNA have been examined. Substitutions of N167 lead to reduced catalytic activity and reduced base flipping. Catalytic activity, base flipping, and covalent conjugate formation were almost completely abolished for the mutant enzymes with substitutions of R200 or R202. CONCLUSIONS: We conclude that R202 plays a similar role in catalysis in Dnmt3a-CD as R232 in M.SssI and R165 in M.HhaI, which could be positioning of the cytosine for nucleophilic attack by a conserved Cys. R200 of Dnmt3a-CD is important in both catalysis and cytosine flipping. Both conserved R200 and R202 are involved in creating and stabilizing of the transient covalent intermediate of the methylation reaction. N167 might contribute to the positioning of the residues from the motif VI, but does not play a direct role in catalysis. PMID- 27001595 TI - The drug industry can help reduce cancer drug costs. PMID- 27001596 TI - Seeing illness in art and medicine: a patient and printmaker collaboration. AB - For many patients, viewing one's illness through medical imaging technology can be an unsettling experience. Patients are likely not to see themselves represented in medical images and may find it difficult to reconcile this new image with their own body image. In this article, a patient with multiple sclerosis and a printmaker describe a collaborative project they have developed, wherein the patient's medical images are incorporated into pieces of fine art. The aim of the project is to open up the interpretation of the ill-body to persons outside the medical field, so as to do justice to the multiple dimensions of the body chronically ill persons often inhabit. PMID- 27001597 TI - Development of syndrome of inappropriate antidiuretic hormone secretion (SIADH) after Onyx embolisation of a cavernous carotid fistula. AB - Patients with cavernous carotid fistulas (CCFs) can present with pituitary hypoperfusion and hypopituitarism; however, there are no previous reports of pituitary or hormonal abnormalities developing after CCF embolisation in an asymptomatic patient. We describe a patient with no hormonal abnormalities who developed syndrome of inappropriate antidiuretic hormone (SIADH) secretion after CCF embolisation. The patient had bilateral indirect CCFs, which were completely embolised via a transvenous approach, and was neurologically stable postoperatively and discharged. In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment. One year later the patient was weaned off all medications and remained neurologically stable. SIADH may be a delayed phenomenon after CCF embolisation. Given the proximity of embolised vessels to the pituitary's vascular supply, CCF treatment may result in flow disturbance, ischaemia and hormonal abnormalities. PMID- 27001598 TI - Giant cell tumour of the femur in a 9-year-old girl, resulting in severe leg length discrepancy. AB - Giant cell tumour of bone (GCTB) is a rare benign tumour noted before physeal closure. GCTB cases in patients younger than 10 years are especially uncommon. The authors report the case of a 9-year-old girl with a GCTB of the distal femur. After initial intralesional excision and curettage of the tumour, local recurrence occurred, which needed two more additional surgeries to treat. The primary tumour and the local relapse invaded the growth plate of the right distal femur, leading to growth disturbance of the femur and requiring leg lengthening using Ilizarov apparatus. Surgeons should note the possibility of this rare condition while treating radiographic lytic lesions even in skeletally immature patients. The occurrence of late limb length discrepancy would be more likely in younger patients. PMID- 27001599 TI - Case of pneumatosis intestinalis and hepatic portal venous gas following a laparoscopic right hemicolectomy. AB - Hepatic portal venous gas (HPVG) in most cases signifies either mechanical migration of air into the portal system due to bowel ischaemia (pneumatosis intestinalis) or portal sepsis due to gas-forming organisms. Successful management of portal sepsis involves early identification of the condition, intensive resuscitation, broad-spectrum antibiotics and a laparotomy for possible bowel ischaemia. In this report, we discuss the case of a patient with pneumatosis intestinalis and HPVG after an elective laparoscopic right hemicolectomy. After an initial slow recovery, on postoperative day seven, the patient had profuse diarrhoea and confusion, and was hyponatraemic. A CT scan revealed pneumatosis intestinalis and HPVG. A laparotomy showed no obvious cause for HPVG and there was no ischaemic bowel. She was managed with intensive care, hyperbaric oxygen therapy, broad-spectrum antibiotics and total-parenteral nutrition. She has made a good recovery. This case highlights the presenting features, differential diagnoses, and management of pneumatosis intestinalis and HPVG. PMID- 27001600 TI - Intraductal papillary mucinous neoplasm presenting with recurrent pancreatitis: a report of a painful 3-decade-long history. AB - Intraductal papillary mucinous neoplasm represents the most common pancreatic cystic neoplasm and harbours significant malignant potential. Duct obliteration can lead to recurrent episodes of pancreatic inflammation mimicking acute and chronic pancreatitis. We report a case of a patient with multiple episodes of idiopathic pancreatitis occurring over a period of three decades. Following admission with severe upper gastrointestinal bleeding, the patient was diagnosed as having invasive pancreatic adenocarcinoma. Examination of the surgical specimen confirmed an intraductal papillary mucinous neoplasm with multiple foci of invasive adenocarcinoma. This case is of significant interest, highlighting the long delay until diagnosis seen in this situation. Intraductal papillary mucinous neoplasm should be considered in the presence of recurrent acute or chronic pancreatitis of unknown aetiology. PMID- 27001601 TI - New insights into paulomycin biosynthesis pathway in Streptomyces albus J1074 and generation of novel derivatives by combinatorial biosynthesis. AB - BACKGROUND: Streptomyces albus J1074 produces glycosylated antibiotics paulomycin A, B and E that derive from chorismate and contain an isothiocyanate residue in form of paulic acid. Paulomycins biosynthesis pathway involves two glycosyltransferases, three acyltransferases, enzymes required for paulic acid biosynthesis (in particular an aminotransferase and a sulfotransferase), and enzymes involved in the biosynthesis of two deoxysugar moieties: D-allose and L paulomycose. RESULTS: Inactivation of genes encoding enzymes involved in deoxysugar biosynthesis, paulic acid biosynthesis, deoxysugar transfer, and acyl moieties transfer has allowed the identification of several biosynthetic intermediates and shunt products, derived from paulomycin intermediates, and to propose a refined version of the paulomycin biosynthesis pathway. Furthermore, several novel bioactive derivatives of paulomycins carrying modifications in the L-paulomycose moiety have been generated by combinatorial biosynthesis using different plasmids that direct the biosynthesis of alternative deoxyhexoses. CONCLUSIONS: The paulomycins biosynthesis pathway has been defined by inactivation of genes encoding glycosyltransferases, acyltransferases and enzymes involved in paulic acid and L-paulomycose biosynthesis. These experiments have allowed the assignment of each of these genes to specific paulomycin biosynthesis steps based on characterization of products accumulated by the corresponding mutant strains. In addition, novel derivatives of paulomycin A and B containing L paulomycose modified moieties were generated by combinatorial biosynthesis. The production of such derivatives shows that L-paulomycosyl glycosyltransferase Plm12 possesses a certain degree of flexibility for the transfer of different deoxysugars. In addition, the pyruvate dehydrogenase system form by Plm8 and Plm9 is also flexible to catalyze the attachment of a two-carbon side chain, derived from pyruvate, into both 2,6-dideoxyhexoses and 2,3,6-trideoxyhexoses. The activity of the novel paulomycin derivatives carrying modifications in the L paulomycose moiety is lower than the original compounds pointing to some interesting structure-activity relationships. PMID- 27001602 TI - Circum-Mediterranean phylogeography of a bat coupled with past environmental niche modeling: A new paradigm for the recolonization of Europe? AB - The isolation of populations in the Iberian, Italian and Balkan peninsulas during the ice ages define four main paradigms that explain much of the known distribution of intraspecific genetic diversity in Europe. In this study we investigated the phylogeography of a wide-spread bat species, the bent-winged bat, Miniopterus schreibersii around the Mediterranean basin and in the Caucasus. Environmental Niche Modeling (ENM) analysis was applied to predict both the current distribution of the species and its distribution during the last glacial maximum (LGM). The combination of genetics and ENM results suggest that the populations of M. schreibersii in Europe, the Caucasus and Anatolia went extinct during the LGM, and the refugium for the species was a relatively small area to the east of the Levantine Sea, corresponding to the Mediterranean coasts of present-day Syria, Lebanon, Israel, and northeastern and northwestern Egypt. Subsequently the species first repopulated Anatolia, diversified there, and afterwards expanded into the Caucasus, continental Europe and North Africa after the end of the LGM. The fossil record in Iberia and the ENM results indicate continuous presence of Miniopterus in this peninsula that most probably was related to the Maghrebian lineage during the LGM, which did not persist afterwards. Using our results combined with similar findings in previous studies, we propose a new paradigm explaining the general distribution of genetic diversity in Europe involving the recolonization of the continent, with the main contribution from refugial populations in Anatolia and the Middle East. The study shows how genetics and ENM approaches can complement each other in providing a more detailed picture of intraspecific evolution. PMID- 27001603 TI - The phylogenetic position and diversity of the enigmatic mongrel frog Nothophryne Poynton, 1963 (Amphibia, Anura). AB - The phylogenetic relationships of the African mongrel frog genus Nothophryne are poorly understood. We provide the first molecular assessment of the phylogenetic position of, and diversity within, this monotypic genus from across its range-the Afromontane regions of Malawi and Mozambique. Our analysis using a two-tiered phylogenetic approach allowed us to place the genus in Pyxicephalidae. Within the family, Nothophryne grouped with Tomopterna, a hypothesis judged significantly better than alternative hypotheses proposed based on morphology. Our analyses of populations across the range of Nothophryne suggest the presence of several cryptic species, at least one species per mountain. Formal recognition of these species is pending but there is a major conservation concern for these narrowly distributed populations in an area impacted by major habitat change. The phylogenetic tree of pyxicephalids is used to examine evolution of life history, ancestral habitat, and biogeography of this group. PMID- 27001604 TI - 187-gene phylogeny of protozoan phylum Amoebozoa reveals a new class (Cutosea) of deep-branching, ultrastructurally unique, enveloped marine Lobosa and clarifies amoeba evolution. AB - Monophyly of protozoan phylum Amoebozoa, and subdivision into subphyla Conosa and Lobosa each with different cytoskeletons, are well established. However early diversification of non-ciliate lobose amoebae (Lobosa) is poorly understood. To clarify it we used recently available transcriptomes to construct a 187-gene amoebozoan tree for 30 species, the most comprehensive yet. This robustly places new genus Atrichosa (formerly lumped with Trichosphaerium) within lobosan class Tubulinea, not Discosea as previously supposed. We identified an earliest diverging lobosan clade comprising marine amoebae armoured by porose scaliform cell-envelopes, here made a novel class Cutosea with two pseudopodially distinct new families. Cutosea comprise Sapocribrum, ATCC PRA-29 misidentified as 'Pessonella', plus from other evidence Squamamoeba. We confirm that Acanthamoeba and ATCC 50982 misidentified as Stereomyxa ramosa are closely related. Discosea have a strongly supported major subclade comprising Thecamoebida plus Glycostylida (suborders Dactylopodina, Stygamoebina; Vannellina) phylogenetically distinct from Centramoebida. Stygamoeba is sister to Dactylopodina. Himatismenida are either sister to Centramoebida or deeper branching. Discosea usually appear holophyletic (rarely paraphyletic). Paramoeba transcriptomes include prokinetoplastid Perkinsela-like endosymbiont sequences. Cunea, misidentified as Mayorella, is closer to Paramoeba than Vexillifera within holophyletic Dactylopodina. Taxon-rich site-heterogeneous rDNA trees confirm cutosan distinctiveness, allow improved conosan taxonomy, and reveal previous dictyostelid tree misrooting. PMID- 27001605 TI - Latin-American-Mediterranean lineage of Mycobacterium tuberculosis: Human traces across pathogen's phylogeography. AB - Currently, Mycobacterium tuberculosis isolates of Latin-American Mediterranean (LAM) family may be detected far beyond the geographic areas that coined its name 15years ago. Here, we established the framework phylogeny of this geographically intriguing and pathobiologically important mycobacterial lineage and hypothesized how human demographics and migration influenced its phylogeography. Phylogenetic analysis of LAM isolates from all continents based on 24 variable number of tandem repeats (VNTR) loci and other markers identified three global sublineages with certain geographic affinities and defined by large deletions RD115, RD174, and by spoligotype SIT33. One minor sublineage (spoligotype SIT388) appears endemic in Japan. One-locus VNTR signatures were established for sublineages and served for their search in published literature and geographic mapping. We suggest that the LAM family originated in the Western Mediterranean region. The most widespread RD115 sublineage seems the most ancient and encompasses genetically and geographically distant branches, including extremely drug resistant KZN in South Africa and LAM-RUS recently widespread across Northern Eurasia. The RD174 sublineage likely started its active spread in Brazil; its earlier branch is relatively dominated by isolates from South America and the derived one is dominated by Portuguese and South/Southeastern African isolates. The relatively most recent SIT33-sublineage is marked with enigmatic gaps and peaks across the Americas and includes South African clade F11/RD761, which likely emerged within the SIT33 subpopulation after its arrival to Africa. In addition to SIT388-sublineage, other deeply rooted, endemic LAM sublineages may exist that remain to be discovered. As a general conclusion, human mass migration appears to be the major factor that shaped the M. tuberculosis phylogeography over large time-spans. PMID- 27001606 TI - Mapping phase diagrams of supported lipid bilayers by atomic force microscopy. AB - In this work, we present the method followed to construct a pseudophase diagram of two phospholipids: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine and 1 palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol). Two different techniques, DSC and AFM, have been used based in the determination of the onset (Tonset ) and completion (Toffset ) temperatures of the gel-to-liquid crystalline phases (Lbeta ->Lalpha ), the first from the endotherms from liposomes and the second from the topographic images of supported lipid bilayers. The features of both phase diagrams are discussed emphasizing the influence of Ca2+ presence and the substrate (mica) on the transition undergone by the phospholipid mixture. Microsc. Res. Tech. 80:4-10, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27001607 TI - Haloparvum sedimenti gen. nov., sp. nov., a member of the family Haloferacaceae. AB - Two extremely halophilic archaeal strains, DYS4T and Y2, were isolated from rock salt of the Jiangcheng Salt Mine, Yunnan province, China. Cells of the two strains were non-motile, pleomorphic rods and Gram-stain-negative. The cells produced light red-pigmented colonies. Strains DYS4T and Y2 required 2.6-3.4 M NaCl, pH 7.5- 8.0 and 42 oC in aerobic conditions for optimal growth. Mg2+ was required for growth. The major polar lipids of both strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and sulfated mannosyl glucosyl diether. An unidentified minor glycolipid spot was present for strains DYS4T and Y2, which differentiates them from the closely related species of the genera Halorubrum and Halopenitus. The lipid core of the glycolipid was sn-2,3-diphytanylglycerol (C20C20). The sequence similarity of the 16S rRNA gene demonstrated that the closest relatives of strains DYS4T and Y2 were Halorubrum aidingense 31-hongT (94.1 % and 93.6 % 16S rRNA gene sequence similarity to DYS4T and Y2, respectively) and Halopenitus salinus SKJ47T (93.4% and 93.1%). Phylogenetic analysis of the 16S rRNA gene and the rpoB' gene revealed that strains DYS4T and Y2 formed an independent lineage closely related to the genera Halorubrum and Halopenitus. The DNA G+C contents of strains DYS4T and Y2 were 68.2 and 67.0 mol%, respectively. The DNA-DNA relatedness value between strains DYS4T and Y2 was 90.0 +/- 0.5%, while that between strain DYS4T and other closest relatives was less than 26 % (19 +/- 0.7 % for Halorubrum aidingense 31-hongT and 25 +/- 0.3% for Halopenitus salinus SKJ47T). The phenotypic, chemotaxonomic and phylogenetic properties suggest that strains DYS4T and Y2 (=CGMCC 1.15000=JCM 30892) represent a novel species of a new genus within the family Haloferacaceae, for which the name Haloparvum sedimenti gen. nov., sp. nov. is proposed. The type strain of the type species is DYS4T (=CGMCC 1.14998T=JCM 30891T). PMID- 27001608 TI - Tools to overcome potential barriers to chlamydia screening in general practice: Qualitative evaluation of the implementation of a complex intervention. AB - BACKGROUND: Chlamydia trachomatis remains a significant public health problem. We used a complex intervention, with general practice staff, consisting of practice based workshops, posters, computer prompts and testing feedback and feedback to increase routine chlamydia screening tests in under 25 year olds in South West England. We aimed to evaluate how intervention components were received by staff and to understand what determined their implementation into ongoing practice. METHODS: We used face-to-face and telephone individual interviews with 29 general practice staff analysed thematically within a Normalisation Process Theory Framework which explores: 1. Coherence (if participants understand the purpose of the intervention); 2. Cognitive participation (engagement with and implementation of the intervention); 3. Collective action (work actually undertaken that drives the intervention forwards); 4. Reflexive monitoring (assessment of the impact of the intervention). RESULTS: Our results showed coherence as all staff including receptionists understood the purpose of the training was to make them aware of the value of chlamydia screening tests and how to increase this in their general practice. The training was described by nearly all staff as being of high quality and responsible for creating a shared understanding between staff of how to undertake routine chlamydia screening. Cognitive participation in many general practice staff teams was demonstrated through their engagement by meeting after the training to discuss implementation, which confirmed the role of each staff member and the use of materials. However several participants still felt unable to discuss chlamydia in many consultations or described sexual health as low priority among colleagues. National targets were considered so high for some general practice staff that they didn't engage with the screening intervention. Collective action work undertaken to drive the intervention included use of computer prompts which helped staff remember to make the offer, testing rate feedback and having a designated lead. Ensuring patients collected samples when still in the general practice was not attained in most general practices. Reflexive monitoring showed positive feedback from patients and other staff about the value of screening, and feedback about the general practices testing rates helped sustain activity. CONCLUSIONS: A complex intervention including interactive workshops, materials to help implementation and feedback can help chlamydia screening testing increase in general practices. PMID- 27001609 TI - Analysis of the structure and function of EMRE in a yeast expression system. AB - The mitochondrial calcium uniporter (MCU) complex is a highly-selective calcium channel, and this complex is believed to consist of a pore-forming subunit, MCU, and its regulatory subunits. As yeast cells lack orthologues of the mammalian proteins, the yeast expression system for the mammalian calcium uniporter subunits is useful for investigating their functions. We here established a yeast expression system for the native-form mouse MCU and 4 other subunits. This expression system enabled us to precisely reconstitute the properties of the mammalian MCU complex in yeast mitochondria. Using this expression system, we analyzed the essential MCU regulator (EMRE), which is a key subunit for Ca(2+) uptake but whose functions and structure remain unclear. The topology of EMRE was revealed: its N- and C-termini projected into the matrix and the inter membrane space, respectively. The expression of EMRE alone was insufficient for Ca(2+) uptake; and co-expression of MCU with EMRE was necessary. EMRE was independent of the protein levels of other subunits, indicating that EMRE was not a protein stabilizing factor. Deletion of acidic amino acids conserved in EMRE did not significantly affect Ca(2+) uptake; thus, EMRE did not have basic properties of ion channels such as ion-selectivity filtration and ion concentration. Meanwhile, EMRE closely interacted with the MCU on both sides of the inner membrane, and this interaction was essential for Ca(2+) uptake. This close interaction suggested that EMRE might be a structural factor for opening of the MCU-forming pore. PMID- 27001610 TI - Effect of atmospheric carbon dioxide levels and nitrate fertilization on glucosinolate biosynthesis in mechanically damaged Arabidopsis plants. AB - BACKGROUND: Increased atmospheric carbon dioxide (CO2) levels predicted to occur before the end of the century will impact plant metabolism. In addition, nitrate availability will affect metabolism and levels of nitrogen-containing defense compounds, such as glucosinolates (GSLs). We compared Arabidopsis foliar metabolic profile in plants grown under two CO2 regimes (440 vs 880 ppm), nitrate fertilization (1 mM vs 10 mM) and in response to mechanical damage of rosette leaves. RESULTS: Constitutive foliar metabolites in nitrate-limited plants show distinct global patterns depending on atmospheric CO2 levels; in contrast, plants grown under higher nitrate fertilization under elevated atmospheric CO2 conditions have a unique metabolite signature. Nitrate fertilization dampens the jasmonate burst in response to wounding in plants grown at elevated CO2 levels. Leaf GSL profile mirrors the jasmonate burst; in particular, indole GSLs increase in response to damage in plants grown at ambient CO2 but only in nitrate-limited plants grown under elevated CO2 conditions. CONCLUSIONS: This may reflect a reduced capacity of C3 plants grown under enriched CO2 and nitrate levels to signal changes in oxidative stress and has implications for future agricultural management practices. PMID- 27001611 TI - Characteristics and prognosis of patients with early-stage endometrial cancer who refuse adjuvant radiotherapy. AB - OBJECTIVE: To investigate the risk factors for refusing adjuvant radiotherapy in patients who have undergone surgery for early-stage endometrial cancer, and to compare their survival rates with patients who have undergone adjuvant radiotherapy. METHODS: Data from the Surveillance, Epidemiology, and End Results database for patients operated on for histologically-proven early-stage endometrioid endometrial cancer, between 1988 and 2012, were screened. Univariate and multivariate logistic regression analyses tested the associations between refusal of adjuvant radiotherapy and demographic, tumoral, and management characteristics. Overall and cancer-related survival rates were compared between 376 patients who refused adjuvant radiotherapy and 752 patients who received adjuvant radiotherapy, matched for demographics (age, race, year of diagnosis, marital status, region), tumoral (grade, FIGO stage, size), and management (lymphadenectomy performed) criteria. RESULTS: 434 of the 16,014 patients (2.7%) who were proposed adjuvant radiotherapy refused this treatment. Older, widowed, divorced, or separated patients, who were recently diagnosed and managed in the Northern plains or Pacific coast (USA), with limited tumoral extension, were more likely to refuse adjuvant radiotherapy. Five-year cancer-related survival was significantly lower in patients who refused adjuvant radiotherapy (88.9% vs. 95.7%, p<0.001) whereas overall survival did not significantly differ between the two groups (76.4% vs. 83.7%, p=0.23). CONCLUSIONS: We have identified the patients' characteristics related to refusal of adjuvant radiotherapy. Refusing adjuvant radiotherapy increased cancer-related death but probably does not reduce overall survival. PMID- 27001612 TI - The High Mobility Group A1 (HMGA1) gene is highly overexpressed in human uterine serous carcinomas and carcinosarcomas and drives Matrix Metalloproteinase-2 (MMP 2) in a subset of tumors. AB - OBJECTIVES: Although uterine cancer is the fourth most common cause for cancer death in women worldwide, the molecular underpinnings of tumor progression remain poorly understood. The High Mobility Group A1 (HMGA1) gene is overexpressed in aggressive cancers and high levels portend adverse outcomes in diverse tumors. We previously reported that Hmga1a transgenic mice develop uterine tumors with complete penetrance. Because HMGA1 drives tumor progression by inducing MatrixMetalloproteinase (MMP) and other genes involved in invasion, we explored the HMGA1-MMP-2 pathway in uterine cancer. METHODS: To investigate MMP-2 in uterine tumors driven by HMGA1, we used a genetic approach with mouse models. Next, we assessed HMGA1 and MMP-2 expression in primary human uterine tumors, including low-grade carcinomas (endometrial endometrioid) and more aggressive tumors (endometrial serous carcinomas, uterine carcinosarcomas/malignant mesodermal mixed tumors). RESULTS: Here, we report for the first time that uterine tumor growth is impaired in Hmga1a transgenic mice crossed on to an Mmp-2 deficient background. In human tumors, we discovered that HMGA1 is highest in aggressive carcinosarcomas and serous carcinomas, with lower levels in the more indolent endometrioid carcinomas. Moreover, HMGA1 and MMP-2 were positively correlated, but only in a subset of carcinosarcomas. HMGA1 also occupies the MMP 2 promoter in human carcinosarcoma cells. CONCLUSIONS: Together, our studies define a novel HMGA1-MMP-2 pathway involved in a subset of human carcinosarcomas and tumor progression in murine models. Our work also suggests that targeting HMGA1 could be effective adjuvant therapy for more aggressive uterine cancers and provides compelling data for further preclinical studies. PMID- 27001613 TI - Deficits in striatal dopamine release in cannabis dependence. AB - Most drugs of abuse lead to a general blunting of dopamine release in the chronic phase of dependence, which contributes to poor outcome. To test whether cannabis dependence is associated with a similar dopaminergic deficit, we examined striatal and extrastriatal dopamine release in severely cannabis-dependent participants (CD), free of any comorbid conditions, including nicotine use. Eleven CD and 12 healthy controls (HC) completed two positron emission tomography scans with [11C]-(+)-PHNO, before and after oral administration of d-amphetamine. CD stayed inpatient for 5-7 days prior to the scans to standardize abstinence. Magnetic resonance spectroscopy (MRS) measures of glutamate in the striatum and hippocampus were obtained in the same subjects. Percent change in [11C]-(+)-PHNO binding potential (DeltaBPND) was compared between groups and correlations with MRS glutamate, subclinical psychopathological and neurocognitive parameters were examined. CD had significantly lower DeltaBPND in the striatum (P=0.002, effect size (ES)=1.48), including the associative striatum (P=0.003, ES=1.39), sensorimotor striatum (P=0.003, ES=1.41) and the pallidus (P=0.012, ES=1.16). Lower dopamine release in the associative striatum correlated with inattention and negative symptoms in CD, and with poorer working memory and probabilistic category learning performance in both CD and HC. No relationships to MRS glutamate and amphetamine-induced subclinical positive symptoms were detected. In conclusion, this study provides evidence that severe cannabis dependence-without the confounds of any comorbidity-is associated with a deficit in striatal dopamine release. This deficit extends to other extrastriatal areas and predicts subclinical psychopathology. PMID- 27001614 TI - Whole-genome sequencing in multiplex families with psychoses reveals mutations in the SHANK2 and SMARCA1 genes segregating with illness. AB - A current focus in psychiatric genetics is detection of multiple common risk alleles through very large genome-wide association study analyses. Yet families do exist, albeit rare, that have multiple affected members who are presumed to have a similar inherited cause to their illnesses. We hypothesized that within some of these families there may be rare highly penetrant mutations that segregate with illness. In this exploratory study, the genomes of 90 individuals across nine families were sequenced. Each family included a minimum of three available relatives affected with a psychotic illness and three available unaffected relatives. Twenty-six variants were identified that are private to a family, alter protein sequence, and are transmitted to all sequenced affected individuals within the family. In one family, seven siblings with schizophrenia spectrum disorders each carry a novel private missense variant within the SHANK2 gene. This variant lies within the consensus SH3 protein-binding motif by which SHANK2 may interact with post-synaptic glutamate receptors. In another family, four affected siblings and their unaffected mother each carry a novel private missense variant in the SMARCA1 gene on the X chromosome. Both variants represent candidates that may be causal for psychotic disorders when considered in the context of their transmission pattern and known gene and disease biology. PMID- 27001615 TI - Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise. AB - Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.+/-6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies. PMID- 27001616 TI - Monoacylglycerol lipase inhibitors produce pro- or antidepressant responses via hippocampal CA1 GABAergic synapses. AB - The probability of suffering the mood disorder depression is up to 30% in women and 15% in men during their life span. Pharmacological options for depression are limited: conventional antidepressants have low efficacy and a delayed onset of action (several weeks). Here we investigate the antidepressant actions of inhibitors of monoacylglycerol lipase (MAGL), the major degradative enzyme of the endocannabinoid 2-arachidonoylglycerol. A low-dose of MAGL inhibitors produces antidepressant effects on acute stress-exposed mice, through glutamatergic synaptic long-term depression (LTD), without significant effects on chronic corticosterone-exposed mice. In contrast, a high-dose of MAGL inhibitors produces pro- or antidepressant effects on acute stress- or chronic corticosterone-exposed mice, respectively, through GABAergic synaptic disinhibition. In the hippocampus, in vivo inhibition of MAGL induces a CB1 cannabinoid receptor (CB1R)-dependent suppression of inhibitory GABAergic synapses and an in vivo LTD of excitatory glutamatergic synapses. LTD induction requires CB1R in astroglial cells (but not in GABAergic or glutamatergic neurons) and postsynaptic glutamate receptors. The conventional antidepressant fluoxetine produces rapid or delayed antidepressant effects in acute stress- or chronic corticosterone-exposed mice, respectively. We propose that depression-like behavior of animals in response to acute stress is the normal behavioral response, and thus, MAGL inhibitors, which produce antidepressant effects in chronic corticosterone-exposed animals through GABAergic synaptic disinhibition, represent a new class of rapidly-acting and long-lasting antidepressants. PMID- 27001618 TI - Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer's disease neuropathological deficits. AB - Extensive evidence has indicated that a high rate of cholesterol biogenesis and abnormal neuronal energy metabolism play key roles in Alzheimer's disease (AD) pathogenesis. Here, for we believe the first time, we used osmotin, a plant protein homolog of mammalian adiponectin, to determine its therapeutic efficacy in different AD models. Our results reveal that osmotin treatment modulated adiponectin receptor 1 (AdipoR1), significantly induced AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) activation and reduced SREBP2 (sterol regulatory element-binding protein 2) expression in both in vitro and in vivo AD models and in Adipo-/- mice. Via the AdipoR1/AMPK/SIRT1/SREBP2 signaling pathway, osmotin significantly diminished amyloidogenic Abeta production, abundance and aggregation, accompanied by improved pre- and post-synaptic dysfunction, cognitive impairment, memory deficits and, most importantly, reversed the suppression of long-term potentiation in AD mice. Interestingly, AdipoR1, AMPK and SIRT1 silencing not only abolished osmotin capability but also further enhanced AD pathology by increasing SREBP2, amyloid precursor protein (APP) and beta-secretase (BACE1) expression and the levels of toxic Abeta production. However, the opposite was true for SREBP2 when silenced using small interfering RNA in APPswe/ind-transfected SH-SY5Y cells. Similarly, osmotin treatment also enhanced the non-amyloidogenic pathway by activating the alpha-secretase gene that is, ADAM10, in an AMPK/SIRT1-dependent manner. These results suggest that osmotin or osmotin-based therapeutic agents might be potential candidates for AD treatment. PMID- 27001619 TI - Clinical impact of five large-scale screening projects for chronic hepatitis B in Chinese migrants in the Netherlands. AB - BACKGROUND & AIMS: In low-endemic countries it is debated whether first generation migrants should be screened for chronic hepatitis B infection. We describe the clinical impact of five large-scale Dutch screening projects for hepatitis B in first-generation Chinese migrants. METHODS: Between 2009 and 2013 five independent outreach screening projects for hepatitis B targeting first generation Chinese migrants were conducted in five main Dutch regions. To explore the relevance of our screening we defined clinical impact as the presence of an indication for: (i) antiviral therapy, (ii) strict follow-up because of high hepatitis B DNA levels and/or (iii) surveillance for hepatocellular carcinoma. RESULTS: In total, 4423 persons participated in the projects of whom 6.0% (n = 264) were HBsAg positive. One hundred and twenty-nine newly diagnosed HBsAg positive patients were analysed in specialist care. Among these patients prevalence of cirrhosis was 6.9% and antiviral therapy for hepatitis B was started in 32 patients (25%). In patients without a treatment indication, strict follow-up because of high hepatitis B DNA levels and/or surveillance for hepatocellular carcinoma was considered indicated in 64 patients (50%). CONCLUSIONS: In our screening project in first-generation Chinese migrants, antiviral treatment, strict follow-up because of high hepatitis B DNA levels and/or surveillance for hepatocellular carcinoma were considered indicated in three of four analysed HBsAg-positive patients. These data show that detection of hepatitis B in Chinese migrants can have considerable impact on patient care. PMID- 27001620 TI - Late Pulmonary Toxicity Associated With Everolimus in a Renal Transplant Patient and Review of the Literature. AB - The use of inhibitors of mammalian target of rapamycin is associated with adverse pulmonary effects. Although sirolimus-related pneumonitis has been well described, reports on pneumonitis with everolimus are scarce. We report a case of everolimus-induced pneumonitis in a renal transplant recipient 5 years after initiation of everolimus treatment, and we also review the literature regarding everolimus-induced pneumonitis in renal transplant patients. PMID- 27001621 TI - Editorial for 31,1. PMID- 27001617 TI - System-based proteomic and metabonomic analysis of the Df(16)A+/- mouse identifies potential miR-185 targets and molecular pathway alterations. AB - Deletions on chromosome 22q11.2 are a strong genetic risk factor for development of schizophrenia and cognitive dysfunction. We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/ mice, a model of the 22q11.2 deletion syndrome. Proteomic results were compared with previous transcriptomic profiling studies of the same brain regions. The aim was to investigate how the combined effect of the 22q11.2 deletion and the corresponding miRNA dysregulation affects the cell biology at the systems level. The proteomic brain profiling analysis revealed PFC and HPC changes in various molecular pathways associated with chromatin remodelling and RNA transcription, indicative of an epigenetic component of the 22q11.2DS. Further, alterations in glycolysis/gluconeogenesis, mitochondrial function and lipid biosynthesis were identified. Metabonomic profiling substantiated the proteomic findings by identifying changes in 22q11.2 deletion syndrome (22q11.2DS)-related pathways, such as changes in ceramide phosphoethanolamines, sphingomyelin, carnitines, tyrosine derivates and panthothenic acid. The proteomic findings were confirmed using selected reaction monitoring mass spectrometry, validating decreased levels of several proteins encoded on 22q11.2, increased levels of the computationally predicted putative miR-185 targets UDP-N-acetylglucosamine-peptide N acetylglucosaminyltransferase 110 kDa subunit (OGT1) and kinesin heavy chain isoform 5A and alterations in the non-miR-185 targets serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform, neurofilament light chain and vesicular glutamate transporter 1. Furthermore, alterations in the proteins associated with mammalian target of rapamycin signalling were detected in the PFC and with glutamatergic signalling in the hippocampus. Based on the proteomic and metabonomic findings, we were able to develop a schematic model summarizing the most prominent molecular network findings in the Df(16)A+/- mouse. Interestingly, the implicated pathways can be linked to one of the most consistent and strongest proteomic candidates, (OGT1), which is a predicted miR-185 target. Our results provide novel insights into system-biological mechanisms associated with the 22q11DS, which may be linked to cognitive dysfunction and an increased risk to develop schizophrenia. Further investigation of these pathways could help to identify novel drug targets for the treatment of schizophrenia. PMID- 27001623 TI - Intercontinental distribution of a new trypanosome species from Australian endemic Regent Honeyeater (Anthochaera phrygia). AB - Establishing a health screening protocol is fundamental for successful captive breeding and release of wildlife. The aim of this study was to undertake a parasitological survey focusing on the presence of trypanosomes in a cohort of Regent Honeyeaters, Anthochaera phrygia, syn. Xanthomyza phrygia (Aves: Passeriformes) that are part of the breeding and reintroduction programme carried out in Australia. We describe a new blood parasite, Trypanosoma thomasbancrofti sp. n. (Kinetoplastida: Trypanosomatidae) with prevalence of 24.4% (20/81) in a captive population in 2015. The sequence of the small subunit rRNA gene (SSU rDNA) and kinetoplast ultrastructure of T. thomasbancrofti sp. n. are the key differentiating characteristics from other Trypanosoma spp. T. thomasbancrofti sp. n. is distinct from Trypanosoma cf. avium found in sympatric Noisy Miners (Manorina melanocephala). The SSU rDNA comparison suggests an intercontinental distribution of T. thomasbancrofti sp. n. and Culex mosquitoes as a suspected vector. Currently, no information exists on the effect of T. thomasbancrofti sp. n. on its hosts; however, all trypanosome-positive birds remain clinically healthy. This information is useful in establishing baseline health data and screening protocols, particularly prior to release to the wild. PMID- 27001624 TI - Deposition, patterning, and utility of conductive materials for the rapid prototyping of chemical and bioanalytical devices. AB - Rapid prototyping is a critical step in the product development cycle of miniaturized chemical and bioanalytical devices, often categorized as lab-on-a chip devices, biosensors, and micro-total analysis systems. While high throughput manufacturing methods are often preferred for large-volume production, rapid prototyping is necessary for demonstrating and predicting the performance of a device and performing field testing and validation before translating a product from research and development to large volume production. Choosing a specific rapid prototyping method involves considering device design requirements in terms of minimum feature sizes, mechanical stability, thermal and chemical resistance, and optical and electrical properties. A rapid prototyping method is then selected by making engineering trade-off decisions between the suitability of the method in meeting the design specifications and manufacturing metrics such as speed, cost, precision, and potential for scale up. In this review article, we review four categories of rapid prototyping methods that are applicable to developing miniaturized bioanalytical devices, single step, mask and deposit, mask and etch, and mask-free assembly, and we will focus on the trade-offs that need to be made when selecting a particular rapid prototyping method. The focus of the review article will be on the development of systems having a specific arrangement of conductive or semiconductive materials. PMID- 27001625 TI - Anti-tumor effect of hot aqueous extracts from Sonchus oleraceus (L.) L. and Juniperus sabina L - Two traditional medicinal plants in China. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sonchus oleraceus (L.) L (SO) and Juniperus sabina L (JS) are traditional medicinal plants in China. And the aqueous extracts of them have been used to treat tumor, inflammatory diseases, infection and so on in Chinese folk culture. However, the underlying mechanisms of their anti-tumor activities have not been illustrated yet. OBJECTIVE: This study aims to evaluate the inhibitory effects of aqueous extracts from SO and JS on tumor cells. MATERIALS AND METHODS: The prepared aqueous extracts of SO and JS were used to treat HepG-2 and K562 tumor cells, while the human peripheral blood mononuclear cells (PBMCs) were set as normal control. The viabilities, cell cycle and apoptosis of tumor cells after extracts treatment were assessed, in addition the expression of apoptosis-related genes (FasL, caspase 3, 6, 7, 8, 9, and 10) were analyzed. Meanwhile, the adherence and migration of HepG-2 were tested, and the expression levels of MMPs and ICAM-1 were analyzed. On top of that, the pSTAT in the two cells were also analyzed and suggested the related signaling pathway that the extracts acted on with in these tumor cells. RESULTS: Results showed that aqueous extracts of SO and JS have inhibitory effects on HepG-2 and K562 cells by decreasing cell viability and inducing apoptosis via up-regulation of the expression of the apoptosis-related genes FasL, caspase 3 and caspase 9. The extracts had different IC50 on tumor cells and PBMCs, which could block the tumor cell cycle at the G(0)/G(1) stage and significantly inhibit the adherence of HepG 2 cells. The extracts inhibited migration of these cells by inhibiting the expression of ICAM-1, MMP-2 and MMP-9. Further study indicated that the inhibition of pSTAT1 and 3 might be responsible for the inhibitory effects of the extracts on tumor cells. DISCUSSION AND CONCLUSION: The results of this study indicated that SO and JS extracts had the anti-tumor effects, which may be developed as novel anti-tumor drugs and used in cancer therapy. PMID- 27001626 TI - (1)H NMR and MS based metabolomics study of the therapeutic effect of Cortex Fraxini on hyperuricemic rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cortex Fraxini (CF) is an important traditional Chinese herbal medicine used for the treatment of gout and hyperuricemia. AIM OF THE STUDY: The aim of this study was to evaluate the anti-hyperuricemic effect of CF on hyperuricemic rats and to investigate its mechanism of action. MATERIALS AND METHODS: Metabolomics based on NMR and MS was used to study the therapeutic effect of CF on hyperuricemic rats. Plasma determination of uric acid (UA) showed that CF treatment markedly improved the UA level. Subsequently, metabolomics analysis was conducted using samples of plasma, kidney and urine, and orthogonal partial least squares-discriminant analysis (OPLS-DA) combined with principal component analysis (PCA) were used to detect potential biomarkers. RESULTS: A total of 26 biomarkers were identified as being primarily involved in amino acid metabolism, lipid metabolism, purine metabolism, amino acid metabolism and carbohydrate metabolism, and hyperuricemia can disturb the balance of many of these metabolic pathways in vivo. CONCLUSIONS: The variations in biomarkers revealed the therapeutic mechanism of CF, and a number of these biomarkers are not only significant for early diagnosis but also for predicting hyperuricemia. PMID- 27001627 TI - Ketamine-Induced Apoptosis in Normal Human Urothelial Cells: A Direct, N-Methyl-d Aspartate Receptor-Independent Pathway Characterized by Mitochondrial Stress. AB - Recreational abuse of ketamine has been associated with the emergence of a new bladder pain syndrome, ketamine-induced cystitis, characterized by chronic inflammation and urothelial ulceration. We investigated the direct effects of ketamine on normal human urothelium maintained in organ culture or as finite cell lines in vitro. Exposure of urothelium to ketamine resulted in apoptosis, with cytochrome c release from mitochondria and significant subsequent caspase 9 and 3/7 activation. The anesthetic mode-of-action for ketamine is mediated primarily through N-methyl d-aspartate receptor (NMDAR) antagonism; however, normal (nonimmortalized) human urothelial cells were unresponsive to NMDAR agonists or antagonists, and no expression of NMDAR transcript was detected. Exposure to noncytotoxic concentrations of ketamine (<=1 mmol/L) induced rapid release of ATP, which activated purinergic P2Y receptors and stimulated the inositol trisphosphate receptor to provoke transient release of calcium from the endoplasmic reticulum into the cytosol. Ketamine concentrations >1 mmol/L were cytotoxic and provoked a larger-amplitude increase in cytosolic Ca(2+) concentration that was unresolved. The sustained elevation in cytosolic Ca(2+) concentration was associated with pathological mitochondrial oxygen consumption and ATP deficiency. Damage to the urinary barrier initiates bladder pain and, in ketamine-induced cystitis, loss of urothelium from large areas of the bladder wall is a reported feature. This study offers first evidence for a mechanism of direct toxicity of ketamine to urothelial cells by activating the intrinsic apoptotic pathway. PMID- 27001630 TI - Electrical double layer effects on ion transfer reactions. AB - The potential dependence of the thermodynamics and kinetics of ion transfer reactions as influenced by the electrical double layer are studied via two dimensional free energy surfaces calculated with an extension of the Anderson Newns Hamiltonian. The Gibbs energy difference between the reduced and oxidized states, the activation barrier and the resulting current-potential curves are investigated as a function of the potential of zero charge and the Debye length, which are applied to characterize the external electric field. It is found that the current-potential curves of different redox systems are distinctly affected by the electrical double layer depending on the charges of the solution-phase and adsorbed species. For the redox couples sensitive to double layer effects, it is shown that the external electric field can cause a decrease in the driving force for the ion transfer process, which leads to the reversible peak current deviating significantly from the ideal, Nernstian predictions and the effective transfer coefficient being less than 1 even though the ion transfer is kinetically fully reversible. PMID- 27001629 TI - Efficacy of docetaxel, cisplatin, and 5-fluorouracil chemotherapy for superficial esophageal squamous cell carcinoma. AB - The anticancer efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy has been reported to be better than that of conventional regimens for advanced or relapsed esophageal squamous cell carcinoma (ESCC), and may become a standard therapy for this disease. Because it is extremely rare for chemotherapy to be administered as treatment for early cancer alone, the efficacy of DCF for superficial ESCC remains unknown. However, from a clinical oncological standpoint, it is important to investigate the anticancer efficacy of chemotherapy for early cancer, which may be useful for understanding the development of treatment resistance against chemotherapy in cancer. This retrospective, single-center analysis included 28 patients with superficial ESCC who received DCF for synchronous head and neck squamous cell carcinoma between June 2007 and July 2013. The response rate to DCF was 60.7%. In 14 of 17 patients who had been judged to have a complete response, local recurrence was eventually confirmed by follow-up esophagogastroduodenoscopy. The median progression-free survival for all 28 patients was 6.0 months. The anticancer efficacy of DCF was not found to be dependent on tumor progression stage or on the volume of local and metastatic tumors but on the drug sensitivity of the individual. Our results suggest that the efficacy of DCF against superficial esophageal squamous cell carcinoma appears to be limited to local lesions and metastases of regional lymph nodes, and the expected effect of DCF for early ESCC is similar to that for advanced, metastatic, or recurrent esophageal cancer. PMID- 27001628 TI - GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer. AB - Human breast cancer precursor cells remain to be elucidated. Using breast cancer gene product GT198 (PSMC3IP; alias TBPIP or Hop2) as a unique marker, we revealed the cellular identities of GT198 mutant cells in human breast tumor stroma. GT198 is a steroid hormone receptor coactivator and a crucial factor in DNA repair. Germline mutations in GT198 are present in breast and ovarian cancer families. Somatic mutations in GT198 are present in ovarian tumor stromal cells. Herein, we show that human breast tumor stromal cells carry GT198 somatic mutations and express cytoplasmic GT198 protein. GT198(+) stromal cells share vascular smooth muscle cell origin, including myoepithelial cells, adipocytes, capillary pericytes, and stromal fibroblasts. Frequent GT198 mutations are associated with GT198(+) tumor stroma but not with GT198(-) tumor cells. GT198(+) progenitor cells are mostly capillary pericytes. When tested in cultured cells, mutant GT198 induces vascular endothelial growth factor promoter, and potentially promotes angiogenesis and adipogenesis. Our results suggest that multiple lineages of breast tumor stromal cells are mutated in GT198. These findings imply the presence of mutant progenitors, whereas their descendants, carrying the same GT198 mutations, are collectively responsible for forming breast tumor microenvironment. GT198 expression is, therefore, a specific marker of mutant breast tumor stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer. PMID- 27001631 TI - Carbon Materials for Lithium Sulfur Batteries-Ten Critical Questions. AB - Lithium-sulfur batteries are among the most promising electrochemical energy storage devices of the near future. Especially the low price and abundant availability of sulfur as the cathode material and the high theoretical capacity in comparison to state-of-the art lithium-ion technologies are attractive features. Despite significant research achievements that have been made over the last years, fundamental (electro-) chemical questions still remain unanswered. This review addresses ten crucial questions associated with lithium-sulfur batteries and critically evaluates current research with respect to them. The sulfur-carbon composite cathode is a particular focus, but its complex interplay with other hardware components in the cell, such as the electrolyte and the anode, necessitates a critical discussion of other cell components. Modern in situ characterisation methods are ideally suited to illuminate the role of each component. This article does not pretend to summarise all recently published data, but instead is a critical overview over lithium-sulfur batteries based on recent research findings. PMID- 27001632 TI - Completely resected follicular dendritic cell sarcoma of the posterior mediastinum: report of a case. AB - Follicular dendritic cell sarcoma is a rare malignant neoplasm originating from follicular dendritic cells, and most of them develop in lymph nodes of the head and neck. One third of follicular dendritic cell sarcomas occur in the extranodal sites such as the tonsils, mesentery, and retroperitoneal organs, but those of mediastinal origin are rare. Here, we present the case of a 16-year-old female with a large follicular dendritic cell sarcoma of posterior mediastinal origin. The tumor was found by a chest X-ray mass examination at her high school, and she had no subjective symptoms or significant past medical history. The tumor was diagnosed as a follicular dendritic cell sarcoma by computed tomography-guided needle biopsy. Although the tumor compressed the mediastinal organs and showed moderate uptake in 18-fluorodeoxyglucose positron emission tomography imaging, it was completely resected through posterolateral incision. Histological examination revealed that spindle-shaped tumor cells formed fascicular or storiform pattern with cellular pleomorphism. By immunohistochemical examination, the tumor cells were found to be positive for CD21 and follicular dendritic cell antigen. Two years after surgery, the patient remains alive with no signs of tumor recurrence. PMID- 27001633 TI - The transport mechanism of the mitochondrial ADP/ATP carrier. AB - The mitochondrial ADP/ATP carrier imports ADP from the cytosol and exports ATP from the mitochondrial matrix, which are key transport steps for oxidative phosphorylation in eukaryotic organisms. The transport protein belongs to the mitochondrial carrier family, a large transporter family in the inner membrane of mitochondria. It is one of the best studied members of the family and serves as a paradigm for the molecular mechanism of mitochondrial carriers. Structurally, the carrier consists of three homologous domains, each composed of two transmembrane alpha-helices linked with a loop and short alpha-helix on the matrix side. The transporter cycles between a cytoplasmic and matrix state in which a central substrate binding site is alternately accessible to these compartments for binding of ADP or ATP. On both the cytoplasmic and matrix side of the carrier are networks consisting of three salt bridges each. In the cytoplasmic state, the matrix salt bridge network is formed and the cytoplasmic network is disrupted, opening the central substrate binding site to the intermembrane space and cytosol, whereas the converse occurs in the matrix state. In the transport cycle, tighter substrate binding in the intermediate states allows the interconversion of conformations by lowering the energy barrier for disruption and formation of these networks, opening and closing the carrier to either side of the membrane in an alternating way. Conversion between cytoplasmic and matrix states might require the simultaneous rotation of three domains around a central translocation pathway, constituting a unique mechanism among transport proteins. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID- 27001634 TI - Ultrasound-Guided Parasternal Block Allows Optimal Pain Relief and Ventilation Improvement After a Sternal Fracture. AB - INTRODUCTION: Sternal fractures are a painful condition which can result in pulmonary morbidity if not treated promptly. The management of isolated fractures has changed from hospital to home-based treatment, provided other major injuries have been excluded. Pain management is the mainstay of treatment. In this case report, we describe how a parasternal block under ultrasound guidance for sternal fracture provided better analgesia thereby improving ventilation. CASE REPORT: A 26-year-old man was admitted to the emergency department following a road traffic accident. His initial evaluation revealed a radio-cubital displaced fracture at the elbow level with severe tenderness over the sternum. Chest X-ray on admission did not reveal any abnormality. On preoperative checkup he was found to have altered chest mechanics with severe pain and tenderness over the sternum. Arterial blood gas (ABG) analysis showed respiratory acidosis. Pulmonary electrical impedance tomography showed hypoventilation of anterior portions of both lungs. An ultrasound examination of the sternum showed a fractured sternum with complete disjunction. An ultrasound-guided bilateral parasternal block was performed which resulted in efficient analgesia and thereby improved his ventilation as indicated by the improvement in ABG. CONCLUSION: Timely and proper analgesia can reduce the pulmonary morbidity in sternal fractures. Of the various analgesic techniques, parasternal block under ultrasound guidance is a relatively simple, safe, and target-specific procedure that can provide efficient pain relief. PMID- 27001635 TI - Reply by Authors. PMID- 27001636 TI - Editorial Comment. PMID- 27001637 TI - Editorial Comment. PMID- 27001638 TI - Editorial Comment. PMID- 27001639 TI - Moderating effects of social engagement on driving cessation in older women. AB - BACKGROUND: Driving cessation in later life is associated with depression. This study examines if social support can buffer the negative effects of driving cessation on older women's mental health. METHODS: Participants were drawn from the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health (ALSWH) and included 4,075 older women (aged 76-87 years) who drove at baseline, following them for three years to assess driving cessation. The outcome variable was mental health, measured by the mental health index (MHI) of the SF-36. The explanatory variables were social support factors, including social interaction, whether the women were living alone or with others, and engagement in social activities. Control variables included age, country of birth, area of residence, ability to manage on income, marital status, and general health. RESULTS: Main effect results showed that poor mental health was predicted by driving cessation, low levels of social interaction, and non-engagement in social activities. There was a significant interaction effect of driving status by social activities engagement on mental health. Women who remained active in their engagement of social activities were able to maintain a good level of mental health despite driving cessation. CONCLUSION: Engagement and participation in social activities can help older women who stopped driving maintain a good level of mental health. PMID- 27001640 TI - Endoscopic ultrasonography is not required for staging malignant esophageal strictures that preclude the passage of a diagnostic gastroscope. AB - BACKGROUND AND AIM: Endoscopic ultrasound (EUS) is considered the most sensitive modality for local staging of esophageal cancer (ECA) and current guidelines recommend EUS in all patients with non-metastatic disease. Our aim was to identify a subset of patients with stenotic, non-metastatic ECA who will not benefit from staging EUS. METHODS: This multicenter study evaluated consecutive patients with newly diagnosed non-metastatic ECA referred for local staging by EUS. All patients had endoscopic evaluation of malignant strictures with 9.8/9.9 mm diagnostic gastroscope prior to EUS. Main outcome measure was to evaluate the relationship between degree of malignant stenosis and tumor staging by EUS. RESULTS: Of 100 patients (median age, 65 years; male 81%), gastroscope could not be advanced past the stricture in 46, all of whom (100%) had locally advanced disease at EUS: T3N0/N+ in 39 and T4N0/N+ in seven. Echoendoscope could not traverse the stricture in any of these patients. Gastroscope could be advanced through the stricture in 54 patients in whom EUS staging was T1N0 in five, T2N0/N+ in eight and T3N0/N+ in 41; echoendoscope could not pass through the stricture in 24 of these 54 (44.4%) patients, all of whom had T3N0/N+ disease. On logistic regression analysis, inability to pass a gastroscope through the stricture was significantly associated with advanced (T3/4) tumor stage (OR = 28.7, 95% CI = 1.64-501.2; P = 0.021). CONCLUSION: Routine EUS examination may not be required in all patients with ECA as the inability to advance a diagnostic gastroscope past a malignant stricture correlates 100% with locally advanced disease on EUS. PMID- 27001641 TI - Sweeteners and health: findings from recent research and their impact on obesity and related metabolic conditions. AB - Few topics in nutrition engender more controversy than added sugars in general, and fructose-containing sugars in particular. Some investigators have argued that added sugars are associated with increased risk of obesity, cardiovascular disease, diabetes, non-alcoholic fatty liver disease and even sugar 'addiction'. Other investigators have questioned the scientific basis for all of these assertions. This debate has extended far beyond the scientific community into various media outlets including the internet and other non-refereed venues often with heated rhetoric and little science. Against this backdrop, a group of experts and researchers in the metabolism and health effects of added sugars presented a symposium 'Sweeteners and Health: Findings from Recent Research and their Impact on Obesity and Related Metabolic Conditions' at the European Congress on Obesity on 7 May 2015. The papers in this supplement are based on the presentations made at this meeting. The current article is intended to serve as an Introduction to this supplement. PMID- 27001642 TI - A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction? AB - Addiction to a wide range of substances of abuse has been suggested to reflect a 'Reward Deficiency Syndrome'. That is, drugs are said to stimulate the reward mechanisms so intensely that, to compensate, the population of dopamine D2 receptors (DD2R) declines. The result is that an increased intake is necessary to experience the same degree of reward. Without an additional intake, cravings and withdrawal symptoms result. A suggestion is that food addiction, in a similar manner to drugs of abuse, decrease DD2R. The role of DD2R in obesity was therefore examined by examining the association between body mass index (BMI) and the Taq1A polymorphism, as the A1 allele is associated with a 30-40% lower number of DD2R, and is a risk factor for drug addiction. If a lower density of DD2R is indicative of physical addiction, it was argued that if food addiction occurs, those with the A1 allele should have a higher BMI. A systematic review found 33 studies that compared the BMI of those who did and did not have the A1 allele. A meta-analysis of the studies compared those with (A1/A1 and A1/A2) or without (A2/A2) the A1 allele; no difference in BMI was found (standardized mean difference 0.004 (s.e. 0.021), variance 0.000, Z=0.196, P<0.845). It was concluded that there was no support for a reward deficiency theory of food addiction. In contrast, there are several reports that those with the A1 allele are less able to benefit from an intervention that aimed to reduce weight, possibly a reflection of increased impulsivity. PMID- 27001643 TI - Added sugars and risk factors for obesity, diabetes and heart disease. AB - The effects of added sugars on various chronic conditions are highly controversial. Some investigators have argued that added sugars increase the risk of obesity, diabetes and cardiovascular disease. However, few randomized controlled trials are available to support these assertions. The literature is further complicated by animal studies, as well as studies which compare pure fructose to pure glucose (neither of which is consumed to any appreciable degree in the human diet) and studies where large doses of added sugars beyond normal levels of human consumption have been administered. Various scientific and public health organizations have offered disparate recommendations for upper limits of added sugar. In this article, we will review recent randomized controlled trials and prospective cohort studies. We conclude that the normal added sugars in the human diet (for example, sucrose, high-fructose corn syrup and isoglucose) when consumed within the normal range of normal human consumption or substituted isoenergetically for other carbohydrates, do not appear to cause a unique risk of obesity, diabetes or cardiovascular disease. PMID- 27001644 TI - What nutritional physiology tells us about diet, sugar and obesity. AB - In this closing perspective, the author exposes why targeting a single nutrient like sugar is in his opinion unlikely to be efficient in preventing obesity and metabolic diseases. He defends the proposal that the concept of fructose toxicity is based on major misconceptions of nutritional physiology. He specifically proposes that (1) sugar being a non-essential nutrient does not obligatorily imply that it has no beneficial effect; (2) alterations of blood triglyceride concentration and hepatic glucose production within the normal range may merely reflect adaptations to a fructose-rich diet rather than early markers of diseases; (3) overfeeding is a normal physiological response to exposure to an energy-dense, palatable nutrient rather than the consequence of 'leptin resistance'; (4) we may presently overemphasize the role of biological regulations and of gene-related heredity when assessing the effects of fructose in particular, and the determinants of obesity in general. PMID- 27001646 TI - Self-healing gold mirrors and filters at liquid-liquid interfaces. AB - The optical and morphological properties of lustrous metal self-healing liquid like nanofilms were systematically studied for different applications (e.g., optical mirrors or filters). These nanofilms were formed by a one-step self assembly methodology of gold nanoparticles (AuNPs) at immiscible water-oil interfaces, previously reported by our group. We investigated a host of experimental variables and herein report their influence on the optical properties of nanofilms: AuNP mean diameter, interfacial AuNP surface coverage, nature of the organic solvent, and nature of the lipophilic organic molecule that caps the AuNPs in the interfacial nanofilm. To probe the interfacial gold nanofilms we used in situ (UV-vis-NIR spectroscopy and optical microscopy) as well as ex situ (SEM and TEM of interfacial gold nanofilms transferred to silicon substrates) techniques. The interfacial AuNP surface coverage strongly influenced the morphology of the interfacial nanofilms, and in turn their maximum reflectance and absorbance. We observed three distinct morphological regimes; (i) smooth 2D monolayers of "floating islands" of AuNPs at low surface coverages, (ii) a mixed 2D/3D regime with the beginnings of 3D nanostructures consisting of small piles of adsorbed AuNPs even under sub-full-monolayer conditions and, finally, (iii) a 3D regime characterised by the 2D full-monolayer being covered in significant piles of adsorbed AuNPs. A maximal value of reflectance reached 58% in comparison with a solid gold mirror, when 38 nm mean diameter AuNPs were used at a water-nitrobenzene interface. Meanwhile, interfacial gold nanofilms prepared with 12 nm mean diameter AuNPs exhibited the highest extinction intensities at ca. 690 nm and absorbance around 90% of the incident light, making them an attractive candidate for filtering applications. Furthermore, the interparticle spacing, and resulting interparticle plasmon coupling derived optical properties, varied significantly on replacing tetrathiafulvalene with neocuproine as the AuNP capping ligand in the nanofilm. These interfacial nanofilms formed with neocuproine and 38 nm mean diameter AuNPs, at monolayer surface coverages and above, were black due to aggregation and broadband absorbance. PMID- 27001645 TI - Physiological handling of dietary fructose-containing sugars: implications for health. AB - Fructose has always been present in our diet, but its consumption has increased markedly over the past 200 years. This is mainly due to consumption of sucrose or high-fructose corn syrup in industrial foods and beverages. Unlike glucose, fructose cannot be directly used as an energy source by all cells of the human body and needs first to be converted into glucose, lactate or fatty acids in the liver, intestine and kidney. Because of this specific two-step metabolism, some energy is consumed in splanchnic organs to convert fructose into other substrates, resulting in a lower net energy efficiency of fructose compared with glucose. A high intake of fructose-containing sugars is associated with body weight gain in large cohort studies, and fructose can certainly contribute to energy imbalance leading to obesity. Whether fructose-containing foods promote obesity more than other energy-dense foods remains controversial, however. A short-term (days-weeks) high-fructose intake is not associated with an increased fasting glycemia nor to an impaired insulin-mediated glucose transport in healthy subjects. It, however, increases hepatic glucose production, basal and postprandial blood triglyceride concentrations and intrahepatic fat content. Whether these metabolic alterations are early markers of metabolic dysfunction or merely adaptations to the specific two-step fructose metabolism remain unknown. PMID- 27001649 TI - Validity and reliability of the Thai version of the leicester cough questionnaire in chronic cough. AB - BACKGROUND: Chronic cough is a common problem potentially disturbing the quality of life (QoL) of coughers. The Leicester Cough Questionnaire (LCQ), previously developed in England, is a validated, self-completed QoL instrument for assessment of chronic cough. This study aimed to develop a Thai version of the LCQ (LCQ-T) and assess its validity and reliability among adult Thai patients with subacute to chronic cough. METHODS: A total of 146 patients with a cough lasting for more than 3 weeks consented to participate in this study and self administered the LCQ-T, together with the following 3 instruments: Borg Cough Scale (BCS), Short Form-36 (SF-36), and Hospital Anxiety Depression Scale (Thai HADS). The LCQ-T was developed by applying a forward-backward translation approach. The LCQ-T comprises 19 items divided into 3 domains: physical (8 items), psychological (7 items), and social (4 items). To validate the LCQ-T, concurrent validity, internal consistency reliability, and test-retest reliability were assessed. RESULTS: Participants included 96 women and 50 men with a mean (SD) age of 59.6 (14.4) years. The concurrent validity comparing LCQ T to BCS yielded statistically significant Pearson correlation coefficients (r= 0.74, P<0.05). The correlation coefficients for SF-36 and Thai-HADS were also significant. The LCQ-T demonstrated very good internal consistency in all domains and the overall scale, with the Cronbach's alpha coefficients ranging from 0.89 to 0.94. The 3-day repeatability of the LCQ-T in 25 clinically stable patients was high with the intra-class correlation coefficients ranging between 0.81 and 0.90. CONCLUSION: LCQ-T is a valid and reliable cough-specific instrument for assessing symptoms and QoL of adult Thai patients with subacute to chronic cough. PMID- 27001650 TI - Aberrant neutrophil function among heavy smokers and chronic obstructive pulmonary disease patients. AB - BACKGROUD: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammation disease of the respiratory tract. The aberrant functions of neutrophils has been reported in COPD patients including respiratory burst and phagocytosis. Unfortunately, there is little evidence of neutrophil functions in healthy smokers who are considered a high risk group for COPD. OBJECTIVE: To determine the alteration of leukocytic parameters, intracellular reactive oxygen species (ROS) levels and phagocytosis percentages among smokers and COPD. METHOD: Sixteen smokers, 17 COPD patients and 10 healthy controls were recruited. The informed consent and recruitment process were ethically approved by the WU-IRB committee. Leukocyte percentages were analyzed by automated cell counter. Polymorphonuclear cells were purified by gradient centrifugation. The cell suspensions were incubated with FITC-conjugated bacteria to allow phagocytosis. Dichlorofluorescin diacetate was loaded to the cells followed by porbol-12-myristyl acetate stimulation to generate ROS. The percentages of phagocytosis and intracellular ROS levels were analyzed using flow cytometry. Mean of leukocyte numbers, mean fluorescence intensities and phagocytosis percentages were compared by t-test using SPSS (version 17). RESULTS: An increased ROS level of circulating neutrophils was observed among heavy smokers and COPD (p<0.05) compared to healthy controls. There was concordance to neutrophil percentages. However, the function on phagocytosis of neutrophils was not abolished in any group of smokers except COPD. CONCLUSIONS: Our findings suggested that the elevation of intracellular ROS generated by circulating neutrophils resulted in pools of inflammatory mediators among heavy smokers, which was suspected as one of the factors causing COPD in high risk people. PMID- 27001651 TI - Biochemical and functional analysis of COS3A, a novel CD63-specific monoclonal antibody. AB - BACKGROUND: Monoclonal antibodies (mAbs) have become essential tools in life science research and in medicine, because of their extreme specificity. Several mAbs against leukocyte surface molecules have been generated in our laboratory. From these, mAb COS3A was selected for biochemical and functional analysis. OBJECTIVE: To analyze the properties and function of the mAb COS3A. METHOD: Cellular distribution was analyzed by immunofluorescence staining and flow cytometry. Biochemical characterization of the molecular target of COS3A was approached by immunoprecipitation, Western blotting and amino acid sequencing using LC-MS. N-glycosidase F treatment of COS3A-precipitated protein and culture of U937 cells in the presence of tunicamycin before cell lysate preparation were used to study the glycosylation state of proteins. Phagocytosis was examined by flow cytometry. RESULTS: MAb COS3A bound specifically to a molecule expressed on the surface of various human hematopoietic cells and cell lines but not on erythrocytes. The antigen had a molecular weight of 30-70 kDa, which was reduced to 25 kDa by elimination of N-linked glycan. LC-MS data and immunoprecipitation indicated that mAb COS3A bound specifically to the CD63 molecule. Remarkably, functional analysis demonstrated that mAb COS3A dramatically reduced granulocyte phagocytosis. CONCLUSIONS: The mAb COS3A recognized the CD63 molecule and strongly diminished granulocyte phagocytosis of E. coli, suggesting that CD63 may play a crucial role in the initial step of phagocytosis. MAb COS3A is, therefore, suitable for both biochemical and functional studies of CD63, and may be used for further study of the mechanism of phagocytosis and also in therapeutic approaches. PMID- 27001653 TI - Cloning and characterization of recombinant tropomyosin of giant freshwater shrimp M. rosenbergii to determine major allergens causing allergic reactions among shrimp-allergic children. AB - BACKGROUND: Seawater and freshwater shrimp are some of the most common causes of food allergy among children in Thailand. Tropomyosin has been reported as a major allergen for shrimp allergic populations around the world. Despite a high number of shrimp-allergic Thai children, however, it is unknown whether shrimp tropomyosin is a major cause of allergic reactions. OBJECTIVES: To clone and characterize tropomyosin of giant freshwater shrimp Macrobrachium rosenbergii (Mr) and determine whether this tropomyosin is a major cross-reactive allergen for Thai children with shrimp allergy. METHODS: Recombinant shrimp Mr tropomyosin (Mac r1.0101) was expressed in yeast Pichia pastoris. Secondary structure composition of purified recombinant Mac r1.0101 was determined by Circular Dichroism. IgE reactivity was examined by immunoblot, direct binding ELISA and inhibition of IgE ELISA using serum from shrimp-allergic children. RESULTS AND CONCLUSION: The amino acid sequence of Mac r1.0101 showed 2 polymorphic amino acids (F44 and S45) indicating a variant of tropomyosin. Purified recombinant Mac r1.0101 obtained a nature-like alpha-helix structure which can be bound by serum specific IgE. The binding affinity of serum-specific IgE to Mac r1.0101 based on the IC50 value was ~1.8 ng/ml. Ten of 13 shrimp-allergic Thai children had serum specific IgE against Mac r1.0101, but at different levels. Results of the inhibition of specific IgE using Mac r1.0101 showed that 7 of the tested serum samples also had specific IgE against other shrimp allergens in addition to IgE against Mac r1.0101. Tropomyosin therefore appears to be a major cross-reactive allergen for Thai children who are allergic to both seawater and giant freshwater shrimp. PMID- 27001652 TI - Serum IFN-gamma-inducible chemokines CXCL9 and CXCL10 are elevated in non immediate drug hypersensitivity reactions. AB - BACKGROUND: The recruitment to the skin of drug-responsive T cells is responsible for the inflammatory profiles of non-immediate drug hypersensitivity reactions (niDHRs). Maculopapular exanthema (MPE) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have quite distinct T cell infiltrating patterns. OBJECTIVE: To investigate serum levels of CXCL9, CXCL10 and IFN-gamma in patients with niDHRs, including MPE and SJS/TEN, to evaluate correlations between the cytokines, and to determine whether the inflammatory factors correlate with clinical severity in patients with SJS/TEN. METHOD: Twenty-four patients with SJS/TEN, 24 patients with MPE, and 24 healthy donors with good tolerance to the drugs involved in the drug reactions were recruited into the study. The modified severity-of-illness score for TEN (SCORTEN) and detachment of body surface area (dBSA) were used to assess the clinical severity of SJS/TEN. Serum levels of CXCL9, CXCL10 and IFN-? were determined by ELISA. RESULTS: The niDHRs group, SJS/TEN and MPE subgroups all exhibited significantly higher levels of CXCL9, CXCL10 and IFN-gamma compared with the control group (P < 0.001). Serum IFN-gamma levels were positively correlated with CXCL9 levels and CXCL10 levels in patients with niDHRs (rs = 0.576, rs = 0.449, P < 0.05). None of the levels of CXCL9, CXCL10 and IFN-gamma had any correlation with modified SCOTEN index or dBSA in SJS/TEN group. CONCLUSIONS: The results suggest Th1 cytokine IFN-gamma and chemokines CXCL9 and CXCL10 may play roles in the pathogenesis of niDHRs. PMID- 27001654 TI - Effects of fastigial nucleus electrostimulation on airway inflammation and remodeling in an experimental rat model of asthma. AB - BACKGROUND: Asthma is a chronic disease involving an immune response, which is characterized by non-specific inflammation and airway remodeling. Glucocorticoids are clinically beneficial in controlling asthma, but further options are needed. In our study, fastigial nucleus electrostimulation (FNS) was applied in a rat asthma model for the first time to investigate the effects of pre-intervention. OBJECTIVE: To observe the effects of FNS on airway inflammation and remodeling in asthmatic rats. METHODS: Forty rats were assigned randomly to the normal control (CON), model (MDL), FNS, or budesonide (BUD) groups. Asthma was induced with chicken egg (OVA). The animals in the CON and MDL groups were treated with normal saline. The animals in the other two groups received FNS or budesonide, respectively. RESULTS: The results indicated that IgE in the serum and airway fiber areas were higher in the MDL group than in other groups. After treatment for 3 weeks, collagen fibers in the bronchial wall in the FNS group were significantly lower compared with the MDL group. CONCLUSION: FNS significantly reduced IL-4, IL-13, TNF-alpha, OVA-IgE and TGF-beta1 in serum and BALF, and increased IFN-gamma. Our results suggest that FNS may ameliorate asthma symptoms and induce changes of cytokines in the serum and lung milieu. PMID- 27001655 TI - Tumour necrosis factor alpha polymorphism (TNF-308alpha G/A) in association with asthma related phenotypes and air pollutants among children in KwaZulu-Natal. AB - BACKGROUND: The study of gene-environment interactions enables us to further understand the pathogenesis of asthma and inflammation. The TNF-alpha gene has been associated with airway pathology in asthma but there is limited information in relation to pollutant exposure and the TNF-alpha 308G/A polymorphism. OBJECTIVE: To determine the risk conferred by the TNF-alpha 308(G/A) polymorphism on respiratory outcome and to evaluate whether the association between exposure to ambient air pollutants such as SO2, NO2, NO, and PM10 and variation in lung function measures is modified by genotype. METHODS: The sample comprised 129 African children (between 9-11 years old). A questionnaire based on guidelines from the British Medical Research Council and the American Thoracic Society was administered to all caregivers to evaluate the prevalence of respiratory symptoms. Atopy was evaluated by skin prick testing. Bihourly measures of lung function (spirometry) were collected at school five days per week over three week periods in each of four seasons (2004-2005) using digital hand-held devices. During each of the four intensive 3-week phases, gaseous air pollutant concentrations were monitored continuously. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-PFLP) analysis was used to detect the TNF-alpha 308 genotype and plasma TNF-alpha levels were measured using the human TNF-alpha Max StandardTM Enzyme-linked immuno-absorbent assay (ELISA) kit. RESULTS: The TNF alpha variant A allele was common among this sample of African children (40% with an allelic frequency of 0.24). There was no significant association with the TNF alpha G/A polymorphism and any respiratory linked phenotype, nor cytokine levels. However, when exposure to pollutants were analyzed with genotypic and phenotypic data, we found relatively modest interaction effects for the TNF-alpha 308 genotype. GEE models showed that children with the TNF-alpha 308 A allele had increased deterioration of lung function post pollution exposure to SO2 [beta=2.62, CI:0.51-4.71, p=0.02 and pint=0.03] and NO [beta=3.28, CI:0.68-5.89, p=0.01, pint=0.03]. CONCLUSION: The TNF-alpha 308 (G/A) polymorphism may be associated with increased pollutant-associated effects on FEV1 intraday variability for both SO2 and NO. The A allele may increase susceptibility to the adverse effects of air pollutants. PMID- 27001656 TI - Age-dependent distribution of the atopic phenotype and allergen sensitization among asthmatic children in southern Taiwan. AB - BACKGROUND: Asthma is divided into atopic and non-atopic phenotypes. The percentages of atopic asthma and allergen sensitization in patients of different ages have not been well studied. OBJECTIVE: To determine the percentage distribution of atopic and non-atopic phenotypes in different age groups of asthmatic children, and investigate the distribution of specific IgE to different allergens when stratified by age group in southern Taiwan. METHOD: We conducted this hospital-based, retrospective, cross-sectional study in southern Taiwan between 2004 and 2006. Asthmatic children aged 3 to 18 years who were diagnosed according to the Global Initiative for Asthma guidelines were enrolled. The MAST CLA system was used to detect 36 allergen-specific IgEs. RESULTS: A total of 620 asthmatic children were divided into three groups: preschool (3-6 years old, n=360), school-aged (7-12 years old, n=213), and adolescent (13-18 years old, n=41) children. The atopic and non-atopic phenotypes were observed in 54.8% and 45.2% of the asthmatic children, respectively. The atopic phenotype was observed in 45.6%, 65.7%, and 80.5% of the preschool, school-aged and adolescent groups, respectively. The percentages of the atopic phenotype were significantly different when stratified by age group (p<0.001), and there was a positive trend of percentage distribution. The percentages of sensitization to aeroallergens were significantly different and observed in 44.0%, 65.7%, and 80.5% of the preschool, school-aged and adolescent groups, respectively (p<0.001). There were positive trends between age groups and prevalence rates of sensitization to the main aeroallergen and other aeroallergen groups, but not to each allergen of the seafood or other food allergen group. CONCLUSIONS: A trend of an increasing percentage of the atopic phenotype when stratified by age group was found in asthmatic children in southern Taiwan. Aeroallergens contributed more to pediatric asthma than food allergens. The prevalence of sensitization to aeroallergens increased with increasing age when stratified by age group. PMID- 27001657 TI - Clinical features of chronic urticaria in aging population. AB - BACKGROUND: Different clinical features of skin diseases have been addressed between aging patients and non-aging patients. However, data focusing on the clinical features of chronic urticaria (CU) in aging patients especially in the Asian population are still limited. OBJECTIVE: This study aimed to investigate the clinical characteristics of CU in aging and non-aging patients in the Asian population. METHODS: Case records of 1622 CU patients attending the Urticaria Clinic, Department of Dermatology, Siriraj Hospital, Mahidol University, Thailand between 2000 and 2013 were retrospectively reviewed. All CU patients older than 60 years were recruited. Twice the number of CU patients who were non-aging were enrolled using a systematic sampling method. RESULTS: Of the 1622 CU patients, 67 (4.1%) were aging patients. From these, 134 non-aging patients with CU were recruited. The majority of patients for both groups were female, with 67.2% and 77.6% of the aging and non-aging groups, respectively. In both groups, the most common cause of CU was chronic spontaneous urticaria. In the aging group, positive autologous serum skin test, anti-thyroid antibodies and antinuclear antibodies were found more commonly than in the non-aging group, without a statistically significant difference. The mean duration of the disease tended to be shorter in the aging group. CONCLUSION: Our study showed that CU in aging patients was uncommon (4.1%). Aging patients with CU seemed to have shorter disease duration and higher percentages of autoantibodies than non-aging patients with CU without a statistically significant difference. PMID- 27001658 TI - Perilla leaf extract prevents atopic dermatitis induced by an extract of Dermatophagoides farinae in NC/Nga mice. AB - BACKGROUND: Perilla (Perilla frutescens Britton) leaf comprises many types of active components, mainly flavonoids, and acts as an anti-inflammatory agent in in vitro and in vivo atopic dermatitis (AD) models. OBJECTIVE: We investigated the effects of orally administered perilla leaf extract (PLE) on the symptoms of AD induced by Dermatophagoides farinae extract (DFE) in NC/Nga AD model mice. METHODS: The mice were allowed free intake of 0.5% PLE. Skin lesions were assessed, and blood was sampled from the caudal vein on days 0, 7, 14, 21, and 31. On day 31, all mice were sacrificed to obtain blood, skin, spleen, and intestinal tissue samples. RESULTS: The assessment scores of the skin lesions and total serum IgE levels of PLE-treated mice (PLE group) were significantly lower than DFE-treated mice (DFE group) on days 7, 14, and 21. On day 31, the serum periostin and thymus and activation-regulated chemokine (TARC) levels in the PLE group were significantly lower than those in the DFE group. Histological analysis of the skin revealed that hyperplasia of the epidermal and dermal layers and infiltration of inflammatory cells (cell infiltration in corium tissues) were suppressed by PLE. Periostin deposition was observed in the skin tissue obtained from the DFE group. Moreover, the CD4+/CD8+ ratio of splenic T cells was suppressed in the PLE group but not in the DFE group. PMID- 27001659 TI - Regulatory T, natural killer T and gammadelta T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison. AB - BACKGROUND: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (gammadelta T) cells may also be dysregulated in CFS/ME and MS. OBJECTIVE: To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls. METHOD: Sixty three volunteers were included in this study: 24 were CFS/ME patients, 11 were MS patients and 27 were healthy controls. Blood samples were obtained from all participants for flow cytometry analysis of iNKT cells, Tregs and gammadelta T cell phenotypes. RESULTS: We observed a significant increase in Tregs in the CFS/ME group (p<=0.05) compared to the healthy control group. Total gammadelta and gammadelta2 T cells were significantly reduced in MS patients in comparison with the healthy control group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and the double-negative iNKT percentage of iNKT significantly decreased compared with the healthy control group. CONCLUSIONS: This study has not identified any immunological disturbances that are common in both MS and CFS/ME patients. However, the differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies. PMID- 27001660 TI - Strategies to improve the immunogenicity of prM+E dengue virus type-2 DNA vaccine. AB - BACKGROUND: An important goal for dengue vaccines is to induce a high and durable level of neutralizing antibody. OBJECTIVE: Three strategies were investigated for improving the immunogenicity of a prM+E dengue serotype 2 (DENV-2) DNA vaccine: 1) expression in two different plasmids; 2) adjustment of dose; and, 3) introduction of the E sequence of Japanese encephalitis virus (JEV) at the carboxy-terminal portion of DENV-2 E. METHOD: Expression cassettes were designed to encode a full-length prM+E sequence of DENV-2 virus employing human-preferred codons (D2prMEopt), or a chimeric prM+E sequence in which the 100-residue carboxy terminal region of E was derived from JEV (D2prMEJE20opt). pHIS and pCMVkan in the presence and absence of CpG motif, respectively, were used for cassette expression. The immunogenicity was compared in mice. RESULTS: Three injections of full-length-D2prMEopt in pHIS and pCMVkan induced a comparable neutralizing antibody titer at post-week-2-injection and post-week-4-injection. The 100-MUg DNA dose induced a numerically but not statistically higher neutralizing antibody titer than the 10-MUg dose. The chimeric-D2prMEJE20opt produced higher extracellular prM and E protein levels in transfected Vero cells, but had a tendency to induce a lower neutralizing antibody titer in mice when compared with the full-length-D2prMEopt. To optimize the immunogenicity of D2prMEopt-DNA candidate, both expression plasmids can be used to generate reproducible high neutralizing titer. A higher dose of DNA immunogen may induce a higher neutralizing antibody response. CONCLUSION: The strategy of the C-terminal region chimeric counterpart with JE20 did not improve but may have reduced the induction of neutralizing antibodies. PMID- 27001661 TI - Identification and expression analysis of the sting gene, a sensor of viral DNA, in common carp Cyprinus carpio. AB - Stimulator of interferon gene (sting) was identified and characterized from common carp Cyprinus carpio. The sting messenger (m)RNA encoded a polypeptide of 402 amino acids with a calculated molecular mass of 46.184 kDa and an isoelectronic point of 6.08. The deduced protein of sting contained a signal peptide, three transmembrane motifs in the N-terminal region and four putative motifs (RXR) found in resident endoplasmic reticulum proteins. mRNA expression of sting was present in twelve investigated tissues, and was up-regulated by koi herpesvirus (KHV) in vivo and in vitro. The transcription of sting was altered by poly(I:C) and poly(dT:dA) stimulation in vitro. The findings suggested that sting is an inducible gene involved in innate immunity against DNA- and RNA-derived pathogens. To investigate defence mechanisms in C. carpio development, sting level in embryos, larvae and juvenile fish was monitored following KHV challenge. The sting message was negligible in embryos prior to hatching, but observed at higher transcriptional levels throughout larval and juvenile stages. Investigation showed the mRNA expression profiles of genes encoding for proteins promoting various functions in the interferon pathway, from pattern recognition receptors to antiviral genes, to be significantly induced in all examined organs by in vivo infection with KHV. Following KHV infection, the ifn message was significantly downregulated in spleen, head kidney, brain and hepatopancreas but notably up-regulated in gill, intestine and skin, suggesting that ifn induction might be related to the mucosal immune system and virus anti-ifn mechanisms. These results provided the basis for further research into the role and mechanisms of sting in fishes. PMID- 27001662 TI - Protective effect of Dunaliella sp., lipid extract rich in polyunsaturated fatty acids, on hepatic and renal toxicity induced by nickel in rats. AB - AIMS: The present study was undertaken to investigate the protective effect of lipid extract of Dunaliella sp. (LE) rich in polyunsaturated fatty acids (PUFA), against oxidative stress induced by nickel in experimental rats. METHODS: Our investigation evaluated the antioxidant activity of LE using both DPPH and NBT assays. Twenty female albino Wistar rats, randomly allocated into four experimental groups, namely (C): control, (Nit): nickel-treated rats with 5 mg/kg/d of NiCl2 during 30 days, (LEa): lipid extract-administered rats with 5 mg/kg BW/d during 30 days and (Nit + LEa): rats treated with Ni and LE administered during 30 days. RESULTS: The in vitro antioxidant activity demonstrated that LE presents an important antioxidant potential. In vivo, the (Nit + LEa) cotreatment decreased the level of malondialdehyde and restored the antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase) in livers and kidneys in comparison with those treated with Ni only. LE administration to rats treated with Ni also ameliorated biochemical and histological parameters as compared to only Ni-treated group. LE of Dunaliella sp., rich in polyunsaturated fatty acids showed a significant hepato- and reno protective effect against metal-induced toxicity. CONCLUSION: LE of Dunaliella sp., rich in PUFA has been proven to be effective in protection against Ni induced toxicity. PMID- 27001663 TI - Betel nut chewing history is an independent prognosticator for smoking patients with locally advanced stage IV head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil. AB - BACKGROUND: Smoking and betel nut chewing are well-known risk factors for head and neck squamous cell carcinoma (HNSCC). Smoking is also a strong prognosticator for patients with locally advanced HNSCC receiving induction chemotherapy. Smoking with or without betel nut chewing is a common practice in Asia. However, little is known regarding whether betel nut chewing can serve as a prognostic factor for smoking patients with locally advanced HNSCC receiving induction chemotherapy. The aim of this study was to evaluate the prognostic impact of betel nut chewing in such patients receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF). METHODS: From January 2010 to December 2012, we retrospectively analyzed 162 smoking patients with locally advanced HNSCC who received induction chemotherapy with TPF at our institution. Background characteristics, including a history of betel nut chewing, were analyzed as potential prognostic factors. RESULTS: Among the 162 smoking patients, 131 patients (81%) were betel nut chewers, while 31 (19%) were non betel nut chewers. One hundred fifty-six (96%) were men, and 6 (4%) were women. The median age was 53 years. The overall response rates to induction chemotherapy were 57 and 77% in patients with and without betel nut chewing history, respectively (P = 0.038). The 2-year progression survival rates were 37 and 67% in patients with and without betel nut chewing history, respectively (P = 0.004). The 2-year overall survival rates were 47 and 71% in patients with and without betel nut chewing history, respectively (P = 0.017). Betel nut chewing history was independently associated with a poor response to induction chemotherapy, an inferior progression-free survival rate, and a poor overall survival rate. CONCLUSIONS: Our results indicate that betel nut chewing history is independently associated with poor prognosis in smoking patients with locally advanced HNSCC receiving induction chemotherapy with TPF. Further investigation is warranted to explain this effect of betel nut chewing history on these patients' prognosis. PMID- 27001664 TI - Genetic polymorphisms to predict gains in maximal O2 uptake and knee peak torque after a high intensity training program in humans. AB - PURPOSE: The study aimed to identify single nucleotide polymorphisms (SNPs) that significantly influenced the level of improvement of two kinds of training responses, including maximal O2 uptake (V'O2max) and knee peak torque of healthy adults participating in the high intensity training (HIT) program. The study also aimed to use these SNPs to develop prediction models for individual training responses. METHODS: 79 Healthy volunteers participated in the HIT program. A genome-wide association study, based on 2,391,739 SNPs, was performed to identify SNPs that were significantly associated with gains in V'O2max and knee peak torque, following 9 weeks of the HIT program. To predict two training responses, two independent SNPs sets were determined using linear regression and iterative binary logistic regression analysis. False discovery rate analysis and permutation tests were performed to avoid false-positive findings. RESULTS: To predict gains in V'O2max, 7 SNPs were identified. These SNPs accounted for 26.0 % of the variance in the increment of V'O2max, and discriminated the subjects into three subgroups, non-responders, medium responders, and high responders, with prediction accuracy of 86.1 %. For the knee peak torque, 6 SNPs were identified, and accounted for 27.5 % of the variance in the increment of knee peak torque. The prediction accuracy discriminating the subjects into the three subgroups was estimated as 77.2 %. CONCLUSIONS: Novel SNPs found in this study could explain, and predict inter-individual variability in gains of V'O2max, and knee peak torque. Furthermore, with these genetic markers, a methodology suggested in this study provides a sound approach for the personalized training program. PMID- 27001665 TI - An exploration of contextual dimensions impacting goals of care conversations in postgraduate medical education. AB - BACKGROUND: Postgraduate medical trainees are not well prepared difficult conversations about goals of care with patients and families in the acute care clinical setting. While contextual nuances within the workplace can impact communication, research to date has largely focused on individual communication skills. Our objective was to explore contextual factors that influence conversations between trainees and patients/families about goals of care in the acute care setting. METHODS: We conducted an exploratory qualitative study involving five focus groups with Internal Medicine trainees (n = 20) and a series of interviews with clinical faculty (n = 11) within a single Canadian centre. Thematic framework analysis was applied to categorize the data and identify themes and subthemes. RESULTS: Challenges and factors enabling goals of care conversations emerged within individual, interpersonal and system dimensions. Challenges included inadequate preparation for these conversations, disconnection between trainees, faculty and patients, policies around documentation, the structure of postgraduate medical education, and resource limitations; these challenges led to missed opportunities, uncertainty and emotional distress. Enabling factors were awareness of the importance of goals of care conversations, support in these discussions, collaboration with colleagues, and educational initiatives enabling skill development; these factors have resulted in learning, appreciation, and an established foundation for future educational initiatives. CONCLUSIONS: Contextual factors impact how postgraduate medical trainees communicate with patients/families about goals of care. Attention to individual, interpersonal and system-related factors will be important in designing educational programs that help trainees develop the capacities needed for challenging conversations. PMID- 27001666 TI - Leveraging protein quaternary structure to identify oncogenic driver mutations. AB - BACKGROUND: Identifying key "driver" mutations which are responsible for tumorigenesis is critical in the development of new oncology drugs. Due to multiple pharmacological successes in treating cancers that are caused by such driver mutations, a large body of methods have been developed to differentiate these mutations from the benign "passenger" mutations which occur in the tumor but do not further progress the disease. Under the hypothesis that driver mutations tend to cluster in key regions of the protein, the development of algorithms that identify these clusters has become a critical area of research. RESULTS: We have developed a novel methodology, QuartPAC (Quaternary Protein Amino acid Clustering), that identifies non-random mutational clustering while utilizing the protein quaternary structure in 3D space. By integrating the spatial information in the Protein Data Bank (PDB) and the mutational data in the Catalogue of Somatic Mutations in Cancer (COSMIC), QuartPAC is able to identify clusters which are otherwise missed in a variety of proteins. The R package is available on Bioconductor at: http://bioconductor.jp/packages/3.1/bioc/html/QuartPAC.html . CONCLUSION: QuartPAC provides a unique tool to identify mutational clustering while accounting for the complete folded protein quaternary structure. PMID- 27001667 TI - Sex-dependent differences in avian malaria prevalence and consequences of infections on nestling growth and adult condition in the Tawny pipit, Anthus campestris. AB - BACKGROUND: Parasites play pivotal roles in host population dynamics and can have strong ecological impacts on hosts. Knowledge of the effects of parasites on hosts is often limited by the general observation of a fraction of individuals (mostly adults) within a population. The aim of this study was to assess the prevalence of malaria parasites in adult (>= 1 year old) and nestling (7-11 day old) Tawny pipits Anthus campestris, to evaluate the influence of the host sex on parasite prevalence in both groups of age, and explore the association between infections and body condition (adults) and growth (nestlings). METHODS: Two hundred Tawny pipits (105 adults and 95 nestlings) from one Spanish population were screened for avian malaria parasites (Haemoproteus and Plasmodium) using the polymerase chain reaction (PCR)-based methods. Body condition (body mass against a linear measure of size) was measured in adults and growth rate (daily mass gain) was calculated for nestlings. RESULTS: The overall prevalence of infection was 46%. Sixteen different mitochondrial cytochrome b haplotypes of Plasmodium spp. and one Haemoproteus spp. haplotype were found. Malaria parasites were equally prevalent in nestlings and adults (45 and 46%, respectively). Males were more likely to be infected by parasites than females, and this sex-bias parasitism was evident in both adults and nestlings. Furthermore, a lower daily mass gain during nestling growth in males than in females following infections were found, whereas the effect of infections on body condition of adults was detrimental for females but not for males. CONCLUSIONS: Age-specific differences in physiological trade-offs and ecological factors, such as nest predation would explain, at least in part, the observed host sex and age-related patterns in Tawny pipits. PMID- 27001669 TI - Association of retirement age with mortality: a population-based longitudinal study among older adults in the USA. AB - BACKGROUND: Retirement is an important transitional process in later life. Despite a large body of research examining the impacts of health on retirement, questions still remain regarding the association of retirement age with survival. We aimed to examine the association between retirement age and mortality among healthy and unhealthy retirees and to investigate whether sociodemographic factors modified this association. METHODS: On the basis of the Health and Retirement Study, 2956 participants who were working at baseline (1992) and completely retired during the follow-up period from 1992 to 2010 were included. Healthy retirees (n=1934) were defined as individuals who self-reported health was not an important reason to retire. The association of retirement age with all cause mortality was analysed using the Cox model. Sociodemographic effect modifiers of the relation were examined. RESULTS: Over the study period, 234 healthy and 262 unhealthy retirees died. Among healthy retirees, a 1-year older age at retirement was associated with an 11% lower risk of all-cause mortality (95% CI 8% to 15%), independent of a wide range of sociodemographic, lifestyle and health confounders. Similarly, unhealthy retirees (n=1022) had a lower all cause mortality risk when retiring later (HR 0.91, 95% CI 0.88 to 0.94). None of the sociodemographic factors were found to modify the association of retirement age with all-cause mortality. CONCLUSIONS: Early retirement may be a risk factor for mortality and prolonged working life may provide survival benefits among US adults. PMID- 27001668 TI - Aminochrome induces dopaminergic neuronal dysfunction: a new animal model for Parkinson's disease. AB - L-Dopa continues to be the gold drug in Parkinson's disease (PD) treatment from 1967. The failure to translate successful results from preclinical to clinical studies can be explained by the use of preclinical models which do not reflect what happens in the disease since these induce a rapid and extensive degeneration; for example, MPTP induces a severe Parkinsonism in only 3 days in humans contrasting with the slow degeneration and progression of PD. This study presents a new anatomy and develops preclinical model based on aminochrome which induces a slow and progressive dysfunction of dopaminergic neurons. The unilateral injection of aminochrome into rat striatum resulted in (1) contralateral rotation when the animals are stimulated with apomorphine; (2) absence of significant loss of tyrosine hydroxylase-positive neuronal elements both in substantia nigra and striatum; (3) cell shrinkage; (4) significant reduction of dopamine release; (5) significant increase in GABA release; (6) significant decrease in the number of monoaminergic presynaptic vesicles; (7) significant increase of dopamine concentration inside of monoaminergic vesicles; (8) significant increase of damaged mitochondria; (9) significant decrease of ATP level in the striatum (10) significant decrease in basal and maximal mitochondrial respiration. These results suggest that aminochrome induces dysfunction of dopaminergic neurons where the contralateral behavior can be explained by aminochrome-induced ATP decrease required both for anterograde transport of synaptic vesicles and dopamine release. Aminochrome could be implemented as a new model neurotoxin to study Parkinson's disease. PMID- 27001671 TI - Cupriavidus nantongensis sp. nov., a novel chlorpyrifos-degrading bacterium isolated from sludge. AB - A Gram-stain-negative, aerobic, coccoid to small rod-shaped bacterium, designated X1T, was isolated from sludge collected from the vicinity of a pesticide manufacturer in Nantong, Jiangsu Province, China. Based on 16S rRNA gene sequence analysis, strain X1T belonged to the genus Cupriavidus, and was most closely related to Cupriavidus taiwanensis LMG 19424T (99.1 % 16S rRNA gene sequence similarity) and Cupriavidus alkaliphilus LMG 26294T (98.9 %). Strain X1T showed 16S rRNA gene sequence similarities of 97.2-98.2 % with other species of the genus Cupriavidus. The major cellular fatty acids of strain X1T were C16 : 0, C16 : 1omega7c and/or iso-C15 : 0 2-OH (summed feature 3), C18 : 1omega7c and C17 : 0 cyclo, and the major respiratory quinone was ubiquinone Q-8. The major polar lipids of strain X1T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid, phospholipid and hydroxyphosphatidylethanolamine. The DNA G+C content was 66.6 mol%. The DNA-DNA relatedness values of strain X1T with the five reference strains C. taiwanensis LMG 19424T, C. alkaliphilus LMG 26294T, Cupriavidus necator LMG 8453T, Cupriavidus gilardii LMG 5886T and 'Cupriavidus yeoncheonense' KCTC 42053 were lower than 70 %. The results obtained from phylogenetic analysis, phenotypic characterization and DNA-DNA hybridization indicated that strain X1T should be proposed to represent a novel species of the genus Cupriavidus, for which the name Cupriavidus nantongensis sp. nov. is proposed. The type strain is X1T (=KCTC 42909T=LMG 29218T). PMID- 27001670 TI - Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia. AB - This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for >=48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for >=7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, P<.001 in propensity score-matched subgroups). Administration of antifungal agents was not associated with A. baumannii VAP (29% vs. 21%, P=.153) but with higher in-hospital mortality (53% vs. 39%, P=.037). Candida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP. PMID- 27001672 TI - General practitioners as educators in adolescent health: a training evaluation. AB - BACKGROUND: General practitioners play an important role in the primary care of adolescents in both community and clinical settings. Yet studies show that GPs can lack confidence, skills and knowledge in adolescent health. This study evaluates the effectiveness of an innovative training intervention on medical participants' knowledge and confidence as adolescent health educators in a school setting. METHODS: 15 general practitioners, 12 general practice registrars and 18 medical students participated in an adolescent health education workshop followed by field experience in health education sessions in secondary schools. The mixed method design included a pre and post intervention survey and focus group interviews. RESULTS: Mean scores on the Confidence to Teach scale increased significantly (3.34 +/- 0.51 to 4.09 +/- 0.33) (p < .001) as did confidence to communicate with adolescents (3.64 +/- 0.48 to 4.19 +/- 0.33) (p < .001). Mean knowledge scores increased significantly (7.00 +/- 1.22 to 8.98 +/- 1.11) (p < .001). Participants highlighted the value of learning about adolescent health issues and generic teaching skills especially lesson planning and design, practicing experiential teaching strategies and finding the 'sweet spot' when communicating with adolescents. Some participants reported that these skills would transfer to the practice setting. CONCLUSION: An applied training intervention that uses evidence-based, experiential teaching strategies and focuses on developing knowledge and practical teaching skills appropriate for the health education of adolescents can enhance knowledge and confidence to engage in community-based adolescent health education. PMID- 27001673 TI - A review of the surgical management of right-sided aortic arch aneurysms. AB - Aneurysms and dissections of the right-sided aortic arch are rare and published data are limited to a few case reports and small series. The optimal treatment strategy of this entity and the challenges associated with their management are not yet fully investigated and conclusive. We performed a systematic review of the literature to identify all patients who underwent surgical or endovascular intervention for right aortic arch aneurysms or dissections. The search was limited to the articles published only in English. We focused on presentation and critically assessed different management strategies and outcomes. We identified 74 studies that reported 99 patients undergoing surgical or endovascular intervention for a right aortic arch aneurysm or dissection. The median age was 61 years. The commonest presenting symptoms were chest or back pain and dysphagia. Eighty-eight patients had an aberrant left subclavian artery with only 11 patients having the mirror image variant of a right aortic arch. The commonest pathology was aneurysm arising from a Kommerell's diverticulum occurring in over 50% of the patients. Twenty-eight patients had dissections, 19 of these were Type B and 9 were Type A. Eighty-one patients had elective operations while 18 had emergency procedures. Sixty-seven patients underwent surgical treatment, 20 patients had hybrid surgical and endovascular procedures and 12 had totally endovascular procedure. There were 5 deaths, 4 of which were in patients undergoing emergency surgery and none in the endovascular repair group. Aneurysms and dissections of a right-sided aortic arch are rare. Advances in endovascular treatment and hybrid surgical and endovascular management are making this rare pathology amenable to these approaches and may confer improved outcomes compared with conventional extensive repair techniques. PMID- 27001674 TI - Outcomes of Fontan conversion for failing Fontan circulation: mid-term results. AB - OBJECTIVES: We investigated the results of a revision of a previous Fontan connection to total cavopulmonary connection (TCPC) in patients with failing Fontan circulation. METHODS: From July 1998 to April 2013, 21 patients who had failing Fontan circulation underwent revision of the previous Fontan operation to TCPC. The median age at TCPC conversion was 17.9 years (range, 4.6-38.1 years) and the median interval between initial Fontan operation and TCPC was 13.8 years (range, 2.1-25.4 years). There were 37 indications for Fontan revision in 21 patients. The indications were huge right atrium (n = 15), atrial arrhythmia (n = 8), intra-atrial thrombi (n = 6), protein-losing enteropathy (PLE) (n = 3) and more than mild atrioventricular valve regurgitation (n = 5). The previous Fontan operation was revised to extracardiac conduit replacement (n = 20) and intra atrial lateral tunnel (n = 1). Concomitant surgery for atrial arrhythmia was performed in 8 patients. Fenestration was performed in 7 patients. The median follow-up duration was 7.1 years (range, 0.3-13.4 years). RESULTS: There were no operative deaths and two late deaths occurred 7.9 and 8.1 years after operation. Actuarial 5- and 10-year survival rates were 92.3 and 83.1%, respectively. Postoperative complications included bleeding (n = 3), deep sternal infection (n = 1) and prolonged pleural effusion for more than 2 weeks (n = 5). During follow up, atrial arrhythmia recurred in 6 patients, PLE recurred in 2 patients and pleural effusion recurred in 2 patients. All patients were classified as New York Heart Association Class I (n = 15) or Class II (n = 4). CONCLUSIONS: Fontan conversion to TCPC in patients with failing Fontan circulation can be performed with low risk of morbidity and mortality. The procedure confers better quality of life and is functional for patients with failed Fontan circulation. PMID- 27001675 TI - Paediatric and congenital cardiac surgery in emerging economies: surgical 'safari' versus educational programmes. AB - To attract the interest of all people potentially involved in humanitarian activities in the emerging economies, in particular giving attention to the basic requirements of the organization of paediatric cardiac surgery activities, the requirements for a successful partnership with the local existing organizations and the basic elements of a patient-centred multidisciplinary integrated approach. Unfortunately, for many years, the interventions in the low and middle income countries were largely limited to short-term medical missions, not inappropriately nicknamed 'surgical safari', because of negative general and specific characteristics. The negative aspects and the limits of the short-term medical missions can be overcome only by long-term educational programmes. The most suitable and consistent models of long-term educational programmes have been combined and implemented with the personal experience to offer a proposal for a long-term educational project, with the following steps: (i) site selection; (ii) demographic research; (iii) site assessment; (iv) organization of surgical educational teams; (v) regular frequency of surgical educational missions; (vi) programme evolution and maturation; (vii) educational outreach and interactive support. Potential limits of a long-term educational surgical programme are: (i) financial affordability; (ii) basic legal needs; (iii) legal support; (iv) non profit indemnification. The success should not be measured by the number of successful operations of any given mission, but by the successful operations that our colleagues perform after we leave. Considering that the children in need outnumber by far the people able to provide care, in this humanitarian medicine there should be plenty of room for cooperation rather than competition. The main goal should be to provide teaching to local staff and implement methods and techniques to support the improvement of the care of the patients in the long run. This review focuses on the organization of paediatric cardiac activities in the emerging economies, but 'the less privileged parts of the world' can be anywhere, not necessarily limited to economic constraints. Lack of diversity because of social, intellectual, educational and professional growth, the last consisting in cultural stagnation, is responsible for the lack of scientific progress and development. PMID- 27001676 TI - Functional Biomedical Images of Alzheimer's Disease. A Green's Function-based Empirical Mode Decomposition Study. AB - Positron emission tomography (PET) provides a functional imaging modality to detect signs of dementias in human brains. Two-dimensional empirical mode decomposition (2D-EMD) provides means to analyze such images. It decomposes the latter into characteristic modes which represent textures on different spatial scales. These textures provide informative features for subsequent classification purposes. The study proposes a new EMD variant which relies on a Green's function based estimation method including a tension parameter to fast and reliably estimate the envelope hypersurfaces interpolating extremal points of the two dimensional intensity distrubution of the images. The new method represents a fast and stable bi-dimensional EMD which speeds up computations roughly 100-fold. In combination with proper classifiers these exploratory feature extraction techniques can form a computer aided diagnosis (CAD) system to assist clinicians in identifying various diseases from functional images alone. PET images of subjects suffering from Alzheimer's disease are taken to illustrate this ability. PMID- 27001677 TI - Intracellular Abeta and its Pathological Role in Alzheimer's Disease: Lessons from Cellular to Animal Models. AB - Accumulation of intraneuronal amyloid-beta peptide (Abeta) appears to be an early event in Alzheimer's disease (AD), suggesting its important role in the neurodegenerative process of AD. It is indicated that intracellular Abeta originates from a portion of Abeta, which is not secreted and consequently remains intracellular, or alternatively from the secreted Abeta, which is internalized into intracellular Abeta pool. A number of cell and transgenic animal models are established to study the pathological role of intracellular Abeta, and to screen for drugs against Abeta aggregation and associated toxicity. Abeta aggregates, particularly oligomers, may lead to synaptic dysfunction and neuronal loss. Screened from high-throughput methods, a number of cellpermeable agents reduce the aggregation of intracellular Abeta and antagonize its cytotoxicity by inhibiting the formation of Abeta oligomers in vivo. The multi functional roles of Abeta in alternate pathways and associated clinical implications for AD treatment are also discussed. PMID- 27001678 TI - Left Anterior Temporal Glucose Metabolism and not Amyloid-beta Load Predicts Naming Impairment in Alzheimer's Disease. AB - Naming impairment in Alzheimer's disease dementia (AD) is associated with atrophy of the left anterior temporal lobe (ATL). We aimed to elucidate if regional cerebral glucose metabolism, as a biomarker of synaptic dysfunction and neurodegeneration, of the left ATL predicts naming impairment, and if amyloid beta (Abeta) deposition, a pathological hallmark of AD, contributes to the prediction. Twenty-nine patients with AD underwent combined [(11)C]PIB and [(18)F]FDG PET examinations for assessment of Abeta load and regional cerebral glucose metabolism. An a priori defined region of interest was used for regional PET analyses of the left ATL. In linear stepwise regression analyses, glucose metabolism of the left ATL was the only significant predictor of naming performance, independent of sex, age, and education. Neither regional nor global Abeta load contributed to the prediction. Left ATL glucose metabolism predicts naming impairment in AD. By contrast, Abeta deposition does not predict naming impairment. PMID- 27001679 TI - Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity. AB - Viruses from the Filoviridae family, as many other virus families, require an acidic pH for successful infection and are therefore susceptible to the actions of 4-aminoquinolines, such as chloroquine. Although the mechanisms of action of chloroquine clearly indicate that it might inhibit filoviral infections, several clinical trials that attempted to use chloroquine in the treatment of other acute viral infections - including dengue and influenza A and B - caused by low pH dependent viruses, have reported that chloroquine had no clinical efficacy, and these results demoted chloroquine from the potential treatments for other virus families requiring low pH for infectivity. The present review is aimed at investigating whether chloroquine could combat the present Ebola virus epidemic, and also at exploring the main reasons for the reported lack of efficacy. Literature was sourced from PubMed, Scopus, Google Scholar, reference list of articles and textbooks - Fields Virology (Volumes 1and 2), the cytokine handbook, Pharmacology in Medicine: Principles and Practice, and hydroxychloroquine and chloroquine retinopathy. The present analysis concludes that (1) chloroquine might find a place in the treatment of Ebola, either as a monotherapy or in combination therapies; (2) the ineffectiveness of chloroquine, or its analogue, hydroxychloroquine, at treating infections from low pH-dependent viruses is a result of the failure to attain and sustain a steady state concentration sufficient to increase and keep the pH of the acidic organelles to approximately neutral levels; (3) to successfully treat filoviral infections - or other viral infections that emerge or emerged from low pH-dependent viruses - a steady state chloroquine plasma concentration of at least 1 ug/mL(~3.125 MUM/L) or a whole blood concentration of 16 MUM/L must be achieved and be sustained until the patients' viraemia becomes undetectable. These concentrations, however, do not rule out the efficacy of other, higher, steady state concentrations - although such concentrations might be accompanied by severe adverse effects or toxicities. The feasibility of the conclusion in the preceding texts has recently been supported by a subsequent study that shows that amodiaquine, a derivative of CQ, is able to protect humans infected with Ebola from death. PMID- 27001680 TI - The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity. AB - Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect. PMID- 27001681 TI - Clonal Mapping of Astrocytes in the Olfactory Bulb and Rostral Migratory Stream. AB - Astrocytes are the most abundant glial population in the central nervous system, where they fulfill multiple essential tasks. Such diverse functions require a heterogeneous population of cells, yet it is still unclear how this cellular heterogeneity emerges during development. To clarify to what extent such diversity is determined by lineage, we have elaborated the first clonal map of astrocytes in the olfactory bulb and rostral migratory stream. Astrocyte clones are comprised of a limited number of cells, which arise from local progenitors and that are arranged following a radial pattern. Although astroglia exhibit a vast morphological diversity, this was layer-dependent rather than determined by lineage. Likewise, lineage did not strictly determine their position, although we found a striking relationship between the clones and olfactory glomeruli. A distinctive morphology and other clonal features, together with the occurrence of immature forms, reflect the singularity of these astroglial populations. PMID- 27001682 TI - Clinicopathological features and surgical outcomes of intraductal tubulopapillary neoplasm of the pancreas: a systematic review. AB - BACKGROUND AND AIMS: Intraductal tubulopapillary neoplasms (ITPNs) of the pancreas are rare. The purpose of this study was to collate and analyze published data on ITPNs of the pancreas to determine the clinicopathological features of the tumors and the surgical outcomes of patients. PATIENTS AND METHODS: We searched MEDLINE and Igakuchuo-Zasshi for the period of 1980 to 2015 for case reports on surgical resection for ITPN of the pancreas. We evaluated the clinicopathological data associated with pancreatic ITPNs, the prognosis for each patient, and surgical outcomes described in the case reports. RESULTS: We obtained clinicopathological data for 58 patients (33 men and 25 women) with a mean age of 61 years (range, 35-84 years) who had undergone surgical resection for ITPN of the pancreas, including one patient from our clinic. Although ITPNs of the pancreas have different clinicopathological features to intraductal papillary mucinous neoplasms, the treatment strategy for patients with ITPNs is the same as for patients with other cystic neoplasms of the pancreas. The immunohistochemical features of ITPNs included testing positive for cytokeratin 7 and/or cytokeratin 19 and negative for trypsin, MUC2, MUC5AC, and fascin. The overall 1-, 3-, and 5-year survival rates after surgery for the 37 cases with available data were 97.3, 80.7, and 80.7 %, respectively. CONCLUSION: Surgical treatment is the only curative management option for patients with ITPN of the pancreas. To determine the best management strategy for this tumor and improve accuracy of prognosis for patients, we will continue to collect and analyze epidemiological and pathological data. PMID- 27001683 TI - Linear compared to circular stapler anastomosis in laparoscopic Roux-en-Y gastric bypass leads to comparable weight loss with fewer complications: a matched pair study. AB - OBJECTIVE: In the course of laparoscopic Roux-en-Y gastric bypass (LRYGB), a tight gastroenterostomy (GE) may lead to higher weight loss but possibly to an increase of local complications such as strictures and ulcers. Different operative techniques for Roux-en-Y reconstruction may also influence the rate of internal hernias, a typical late complication of LRYGB. The objective of this study was to compare weight loss, rates of strictures, internal hernias, and ulcerations of linear versus circular stapler anastomosis. METHODS: Retrospective analysis of prospectively collected data in a 3:1-matched pair study. A total of 228 patients with a minimal follow-up of 2 years were matched according to BMI at baseline, age, and gender. The follow-up rate was 100 % at 1 and 2 years postoperatively; the mean follow-up time was 3.8 +/- 1.63 years. In group C (circular), 57 patients were operated with a 25-mm circular stapler technique (average BMI 44.7 +/- 5.18 kg/m(2), age 44.1 +/- 10.8 years, 80.7 % female). In group L (linear), 171 patients were operated using a linear stapler (approximately 30 mm, average BMI 43.8 +/- 5.24 kg/m(2), age 43.7 +/- 12.5 years, 70.8 % female). A propensity score matching and a logrank test were used for statistical analysis. RESULTS: The average excessive BMI loss (EBMIL) after 1 year was not statistically different (70.6 +/- 20.2 % in group C vs 72.5 +/- 20.4 % in group L) as well as after 2 years (71.6 +/- 22.5 % in group C vs 74.6 +/- 19.6 % in group L). The average operation time was 155 +/- 53 min in group C and 109 +/- 57 min in group L (p = 0.0001). In group L, patients had significantly lower overall stricture rates at the GE compared to group C (0 [0 %] vs. 4 [7 %], p = 0.0004), a lower rate and severity of internal hernias (10 [5.8 %] vs. 7 [12.3 %] p = 0.466), and equal local ulcerations rates (3 [1.8 %] vs. 1 [1.8 %] p = 0.912). CONCLUSION: Linear stapler anastomosis in LRYGB compared to circular anastomosis leads to equal weight loss and less strictures. The lower rate of internal hernias in linear stapler anastomosis was not significantly different. PMID- 27001686 TI - Gravitational collapse of depletion-induced colloidal gels. AB - We study the ageing and ultimate gravitational collapse of colloidal gels in which the interparticle attraction is induced by non-adsorbing polymers via the depletion effect. The gels are formed through arrested spinodal decomposition, whereby the dense phase arrests into an attractive glass. We map the experimental state diagram onto a theoretical one obtained from computer simulations and theoretical calculations. Discrepancies between the experimental and simulated gel regions in the state diagram can be explained by the particle size and density dependence of the boundary below which the gel is not strong enough to resist gravitational stress. Visual observations show that gravitational collapse of the gels falls into two distinct regimes as the colloid and polymer concentrations are varied, with gels at low colloid concentrations showing the onset of rapid collapse after a delay time. Magnetic resonance imaging (MRI) was used to provide quantitative, spatio-temporally resolved measurements of the solid volume fraction in these rapidly collapsing gels. We find that during the delay time, a dense region builds up at the top of the sample. The rapid collapse is initiated when the gel structure is no longer able to support this dense layer. PMID- 27001685 TI - Modeling the integration of bacterial rRNA fragments into the human cancer genome. AB - BACKGROUND: Cancer is a disease driven by the accumulation of genomic alterations, including the integration of exogenous DNA into the human somatic genome. We previously identified in silico evidence of DNA fragments from a Pseudomonas-like bacteria integrating into the 5'-UTR of four proto-oncogenes in stomach cancer sequencing data. The functional and biological consequences of these bacterial DNA integrations remain unknown. RESULTS: Modeling of these integrations suggests that the previously identified sequences cover most of the sequence flanking the junction between the bacterial and human DNA. Further examination of these reads reveals that these integrations are rich in guanine nucleotides and the integrated bacterial DNA may have complex transcript secondary structures. CONCLUSIONS: The models presented here lay the foundation for future experiments to test if bacterial DNA integrations alter the transcription of the human genes. PMID- 27001684 TI - Ruptured abdominal aortic aneurysm-epidemiology, predisposing factors, and biology. AB - PURPOSE: Abdominal aortic aneurysm is a common degenerative vascular disorder associated with sudden death due to aortic rupture. This review describes epidemiology, predisposing factors, and biology of ruptured abdominal aortic aneurysms (rAAAs). METHODS: Based on a selective literature search in Medline (PubMed), original publications, meta-analyses, systematic reviews, and Cochrane reviews were evaluated for rAAA. RESULTS: The hospital admission rate for rAAA is decreasing and is now in the range of approximately 10 per 100,000 population in men. Smoking contributes to about 50 % of population risk for rupture or surgically treated AAA. AAA rupture is a multifaceted biological process involving biochemical, cellular, and proteolytic influences, in addition to biomechanical factors. AAA rupture occurs when the stress (force per unit area) on the aneurysm wall exceeds wall strength. Proteolytic activities of matrix metalloproteinases have been implicated in aneurysm wall weakening and rupture. Aneurysm diameter is the most prominent predisposing factor for aneurysm growth and rupture. Wall stress, aneurysm shape and geometry, intraluminal thrombus, wall thickness, calcification, and metabolic activity influence the rupture risk. CONCLUSION: The best conservative option to avoid AAA rupture consists in smoking cessation and control of hypertension. Many biological factors influence rupture risk. PMID- 27001687 TI - The influence of a novel simulated learning environment upon student clinical subjective refraction performance: A pilot study. AB - BACKGROUND: Optometry students are taught the process of subjective refraction through lectures and laboratory-based practicals before progressing to supervised clinical practice. Simulated leaning environments (SLEs) form part of an emerging technology used in a range of health disciplines; however, there is limited evidence regarding the effectiveness of clinical simulators as educational tools. METHODS: Forty optometry students (20 fourth year and 20 fifth year) were assessed twice by a qualified optometrist (two examinations separated by four to eight weeks), while completing a monocular non-cycloplegic subjective refraction on the same patient with an unknown refractive error, simulated using contact lenses. Half of the students were granted access to an online simulated learning environment, The Brien Holden Vision Institute (BHVI) Virtual Refractor, and the remaining students formed a control group. The primary outcome measures at each visit were; accuracy of the clinical refraction compared to a qualified optometrist and relative to the Optometry Council of Australia and New Zealand (OCANZ) subjective refraction examination criteria. Secondary measures of interest included descriptors of student SLE engagement, student self-reported confidence levels and correlations between performance in the simulated and real world clinical environment. RESULTS: Eighty per cent of students in the intervention group interacted with the simulated learning environment (for an average of 100 minutes); however, there was no correlation between measures of student engagement with the BHVI Virtual Refractor and speed or accuracy of clinical subjective refractions. Fifth year students were typically more confident and refracted more accurately and more quickly than fourth year students. A year group by experimental group interaction (p = 0.03) was observed for accuracy of the spherical component of refraction and post hoc analysis revealed that less experienced students exhibited greater gains in clinical accuracy following exposure to the SLE intervention. CONCLUSIONS: Short-term exposure to a SLE can positively influence clinical subjective refraction outcomes for less experienced optometry students and may be of benefit in increasing the skills of novice refractionists to levels appropriate for commencing supervised clinical interactions. PMID- 27001688 TI - Beyond bicarbonate: complete acid-base assessment in patients receiving intermittent hemodialysis. AB - Background: Acid-base assessments in hemodialysis patients have been limited almost entirely to measurements of total CO 2 concentration, and assumptions have been made about the presence of acid-base disorders. To gain a fuller understanding of the acid-base status of stable hemodialysis patients, we analyzed measurements of pCO 2 , pH and HCO 3 - obtained in a cohort of chronic stable hemodialysis patients over a 5-year period. Methods: We reviewed acid-base measurements taken pre-dialysis from fistula blood in 53 outpatients receiving hemodialysis thrice weekly between 2008 and 2012. In these patients, pH and pCO 2 were measured using an onsite blood gas analyzer, and HCO 3 - was computed. Relevant clinical and laboratory data were obtained from medical records. Factors affecting serum HCO 3 - were identified. Simple and mixed acid-base disorders were diagnosed using accepted rules. Results: Serum HCO 3 - was affected by age, normalized protein catabolic rate, interdialytic weight gain and length of interval between treatments. As expected, metabolic acidosis was the most common acid-base disorder, but respiratory acid-base disturbances, as simple or complex disorders, were found in 41% of the measurements. Respiratory alkalosis was seen more frequently than respiratory acidosis, but the latter disorder was more commonly associated with serious comorbidities. Conclusions: Respiratory acid base disorders are an important component of the acid-base abnormalities seen in hemodialysis patients and are not identified by measuring total CO 2 concentration; hence, complete acid-base measurements are needed to determine the components of hemodialysis patients' acid-base status that are contributing to mortality risk. PMID- 27001689 TI - ? PMID- 27001690 TI - Anthropogenic effects on bacterial diversity and function along a river-to estuary gradient in Northwest Greece revealed by metagenomics. AB - Studies assessing the effects of anthropogenic inputs on the taxonomic and functional diversity of bacterioplankton communities in lotic ecosystems are limited. Here, we applied 16S rRNA gene amplicon and whole-genome shotgun sequencing to examine the microbial diversity in samples from the Kalamas River (Northwest Greece), a mid-size river that runs through agricultural and NATURA protected areas, but also receives urban sewage from a large city through a manmade ditch. Samples from three different locations between the exit of the ditch and the estuary, during three different months showed that temporal differences of taxonomic and functional diversity were more pronounced than spatial ones, and <1% of total taxa were shared among all samples, revealing a highly dynamic ecosystem. Comparisons of gene diversity with other aquatic habitats showed that only the high flow winter samples resembled more to freshwater environments while samples during the decreased water flow months were dominated by sewage inputs and soil-related organisms. Notably, microbial human gut signals were detectable over background freshwater and soil/runoff related signals, even at tens of kilometers downstream the city. These findings revealed the significance of allochthonous inputs on the composition and dynamics of river bacterial communities, and highlighted the potential of metagenomics for source tracking purposes. PMID- 27001691 TI - Fast solid-phase extraction of N-linked glycopeptides by amine-functionalized mesoporous silica nanoparticles. AB - Selective enrichment is a crucial step before the mass spectrometric analysis of glycoproteins. A new approach using 3-aminopropyltriethoxysilane (APTES) functionalized mesoporous silica materials (SBA-15) was reported to enrich the glycoproteins. Selective extraction of glycopeptides was achieved through coupling the oxidized glycan chains on the glycopeptides with the amine groups on SBA-15 through a reductive amination reaction, then the captured glycopeptides were detached from the SBA-15 for the following MS analysis using the enzyme PNGase F. Because the mesoporous material has a confinement effect, the efficiency of enrichment and enzymatic deglycosylation was improved dramatically. The coupling time was shortened from 4 hours to 1 hour, and the deglycosylation time was greatly shortened from 6 hours to 3 hours. This approach was successfully applied to profile the N-glycoproteome of human colorectal cancer serum. 84 N-linked glycosylation sites from 56 N-linked glycoproteins were identified from as little as 5 MUL serum. PMID- 27001692 TI - Cathepsin K osteoporosis trials, pycnodysostosis and mouse deficiency models: Commonalities and differences. AB - INTRODUCTION: The osteoporosis market reached a value of more than $11 billion in 2015. Current treatments remain mostly antiresorptive and comprise of bisphosphonates, the anti-RANKL antibody, denusomab, and selective estrogen receptor modulators (SERMs). The most promising novel antiresorptives are cathepsin K inhibitors, which selectively target the bone matrix, degrading protease without interfering with osteoclast viability or formation as all other antiresorptives do. AREAS COVERED: This review analyses the current status of cathepsin K inhibitor development, its side effects, and compares the phenotypes of mouse and human cathepsin K deficiencies with drug treatment outcomes. EXPERT OPINION: Several selective cathepsin K inhibitors have been developed and evaluated in preclinical and clinical studies. Although all compounds were effective in reducing bone resorption markers, the development of some compounds was terminated either due to side effects or market competition. The most advanced compound is odanacatib, which significantly reduced bone fracture rates in a 5-year trial but still exhibits safety concerns. The analysis of mouse and human catK deficiencies sheds some light on the consequences of a cathepsin K inhibitor treatment. How predictive the knockout phenotypes are regarding long term cathepsin K treatment remains unclear. Clearly, more studies are needed to understand the mechanism of the observed side effects and novel approaches are needed to make CatK inhibitors either osteoclast-specific or selective for the inhibition of the collagen matrix without affecting the other activities of the protease. PMID- 27001693 TI - R-process enrichment from a single event in an ancient dwarf galaxy. AB - Elements heavier than zinc are synthesized through the rapid (r) and slow (s) neutron-capture processes. The main site of production of the r-process elements (such as europium) has been debated for nearly 60 years. Initial studies of trends in chemical abundances in old Milky Way halo stars suggested that these elements are produced continually, in sites such as core-collapse supernovae. But evidence from the local Universe favours the idea that r-process production occurs mainly during rare events, such as neutron star mergers. The appearance of a plateau of europium abundance in some dwarf spheroidal galaxies has been suggested as evidence for rare r-process enrichment in the early Universe, but only under the assumption that no gas accretes into those dwarf galaxies; gas accretion favours continual r-process enrichment in these systems. Furthermore, the universal r-process pattern has not been cleanly identified in dwarf spheroidals. The smaller, chemically simpler, and more ancient ultrafaint dwarf galaxies assembled shortly after the first stars formed, and are ideal systems with which to study nucleosynthesis events such as the r-process. Reticulum II is one such galaxy. The abundances of non-neutron-capture elements in this galaxy (and others like it) are similar to those in other old stars. Here, we report that seven of the nine brightest stars in Reticulum II, observed with high resolution spectroscopy, show strong enhancements in heavy neutron-capture elements, with abundances that follow the universal r-process pattern beyond barium. The enhancement seen in this 'r-process galaxy' is two to three orders of magnitude higher than that detected in any other ultrafaint dwarf galaxy. This implies that a single, rare event produced the r-process material in Reticulum II. The r-process yield and event rate are incompatible with the source being ordinary core-collapse supernovae, but consistent with other possible sources, such as neutron star mergers. PMID- 27001695 TI - Understanding the Zr and Si interdispersion in Zr1-xSixO2 mesoporous thin films by using FTIR and XANES spectroscopy. AB - Zr-Si mixed mesoporous oxides were obtained in a wide range of proportions, from 0 to 30% and from 70 to 100% of Si, using Si(OEt)4 and ZrCl4 as precursors and Pluronic F127 as a template. The oxide mesostructure was characterized by transmission electron microscopy and 2D-small angle X-ray scattering. Fourier transform infrared spectroscopy measurements suggested a local homogeneous interdispersion of both cations. Further selective studies using X-ray Absorption Near Edge Structure (XANES) spectroscopy for separately Zr and Si local environments, allowed for demonstrating that the Zr coordination varies from close to 7 to 6, when its concentration in the mixed oxide is reduced. In addition, it was possible to determine that in mixed oxides with low Zr concentrations, Zr can fit into the spaces occupied by Si in SiO2 pure oxide. An equivalent XANES result was obtained for Si, which is also compatible with the information obtained by FTIR. Furthermore, the Zr-O distance varied from close to 2.2 A to 1.7 A when the Zr concentration decreased. Finally, our study also demonstrates the usefulness of XANES to selectively assess the local structure (coordination, symmetry and chemical state) of specific atoms in nanostructured systems. PMID- 27001694 TI - A specific area of olfactory cortex involved in stress hormone responses to predator odours. AB - Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising <5% of the olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents. PMID- 27001703 TI - Neonatal malnutrition programs the oxidant function of macrophages in response to Candida albicans. AB - Experimental maternal nutrition restriction models are used to investigate short or long-term consequences of nutritional deficiency on puppies' growth. By assuming that the immune function is directly related to host's nutritional status, the current study aims to investigate the effects of neonatal malnutrition on oxidative stress and on the cell death of the alveolar macrophage after in vitro infection by Candida albicans. Wistar rats were suckled by mothers fed on diets containing 17% protein (Nourished group) or 8% protein (Malnourished group) in the current assay. Both groups received the standard diet used in the vivarium until adulthood, after weaning. The results showed that the offspring from mothers fed on low-protein diet presented lower body weight from 5 days of life on. Their low weight remained until adulthood when it was compared to that of rats in the nourished group. Superoxide and nitric oxide production was lower in malnourished animals and it was accompanied by low inducible nitric oxide synthase gene expression levels in systems in which the alveolar macrophages were challenged by immunogenic stimulus. No significant differences were observed in comparisons performed between the nourished and malnourished groups in any of the analyzed cell viability (apoptosis/necrosis) parameters. The fungal inoculum stimulated system induced higher oxidative stress and cell death by necrosis. The current study demonstrated that dietary restriction during lactation alters the oxidant function of alveolar macrophages in puppies; It happens from the gene transcription step to the release of mediators, thus compromising the host's defenses against Candida albicans. It raises the possibility that Candida albicans may cease to be a commensal fungus to become a pathogen in offspring that have suffered nutritional deficiency during critical developmental periods, due to impaired immune responses. PMID- 27001704 TI - How people with dementia and their families decide about moving to a care home and support their needs: development of a decision aid, a qualitative study. AB - BACKGROUND: People with dementia and their relatives find decisions about the person with dementia living in a care home difficult. METHODS: We interviewed 20 people with dementia or family carers around the time of this decision in order to design a decision-aid. RESULTS: Decision-makers balanced the competing priorities of remaining somewhere familiar, family's wish they remain at home, reduction of risk and effects on carer's and person with dementia's physical health. The person with dementia frequently resented their lack of autonomy as decisions about care home moves were made after insight and judgment were impaired. Family consultation usually helped carers but sometimes exacerbated tensions. Direct professional support was appreciated where it was available. There is a need for healthcare professionals to facilitate these conversations around decision-making and to include more than signposting to other organisations. CONCLUSIONS: There is a need for a healthcare professional facilitated decision-aid. This should detail what might change for the person with dementia and their carer, possible resources and alternatives and assist in facilitating discussion with the wider family; further research will develop and test a tool to facilitate decision making about place of care needs. PMID- 27001705 TI - Evaluation of two multi-locus sequence typing schemes for commensal Escherichia coli from dairy cattle in Washington State. AB - Multi-locus sequence typing (MLST) is a useful system for phylogenetic and epidemiological studies of multidrug-resistant Escherichiacoli. Most studies utilize a seven-locus MLST, but an alternate two-locus typing method (fumC and fimH; CH typing) has been proposed that may offer a similar degree of discrimination at lower cost. Herein, we compare CH typing to the standard seven locus method for typing commensal E. coli isolates from dairy cattle. In addition, we evaluated alternative combinations of eight loci to identify combinations that maximize discrimination and congruence with standard seven locus MLST among commensal E. coli while minimizing the cost. We also compared both methods when used for typing uropathogenic E. coli (UPEC). CH typing was less discriminatory for commensal E. coli than the standard seven-locus method (Simpson's Index of Diversity=0.933 [0.902-0.964] and 0.97 [0.96-0.979], respectively). Combining fimH with housekeeping gene loci improved discriminatory power for commensal E. coli from cattle but resulted in poor congruence with MLST. We found that a four-locus typing method including the housekeeping genes adk, purA, gyrB and recA could be used to minimize cost without sacrificing discriminatory power or congruence with Achtman seven-locus MLST when typing commensal E. coli. PMID- 27001706 TI - Dementia-specific quality of life instruments: a conceptual analysis. AB - BACKGROUND: Over the past 20 years, many researchers have worked in developing various methods for measuring quality of life (QoL) of people with dementia. The aim of this review is to develop the conceptual frameworks of the dementia specific QoL instruments, to identify their evolution over time and to provide elements of reflection on the QoL concept in dementia and its evaluation. METHODS: An electronic search was conducted on PsycINFO and MEDLINE databases, from January 1985 to June 2015 using a combination of key words that include QoL, dementia, and review. RESULTS: The analysis of the conceptual frameworks of the 18 selected dementia-specific QoL tools shows a great diversity in: (1) the QoL definitions (e.g. health-related QoL definitions, QoL definitions based on Lawton's work, or similar to this latter); (2) the theoretical QoL models (e.g. Lawton' work and modified Lawton, adaptation, personhood); (3) the domains and dimensions; (4) the way to construct the instrument (e.g. development based on literature, opinion of the experts), and (5) the items' formulation (e.g. use of criterion of intensity or frequency). CONCLUSIONS: There are different conceptual frameworks in the dementia-specific QoL measures with improvements over time (e.g. inclusion of interesting concepts such as adaptation, taking into account the views of patients themselves). Each of the conceptual parameters (definitions, models, domains, and dimensions) is discussed to identify the scales that are conceptually the strongest. Through their review, recommendations for future instrument refinement and development are discussed and a new QoL definition is proposed. PMID- 27001707 TI - Evaluation of spray application methods for navel orangeworm control in almonds. AB - BACKGROUND: Gear Up/Throttle Down (GUTD) and Inward Only strategies represent potential alternatives to conventional airblast applications to reduce spray drift. This study evaluates Inward Only and a modified version of GUTD in almonds, the largest US tree crop, at the recommended hull split treatment timing for control of navel orangeworm (NOW), the key almond insect pest. RESULTS: Conventional treatment produced the most drift (15.6% of total bifenthrin load), while the GUTD and Inward Only treatments produced only 7.6 and 9.7% respectively. For all methods, 92-94% of the drift was found in the first 15.2 m downwind of the orchard. NOW control was lower for the Inward Only treatment compared with the GUTD and conventional treatments. NOW control was consistently lower at 4.88 m height relative to 2.44 m in all treatments, reflecting the reduced deposition higher in the tree canopy recorded in deposition samples. CONCLUSION: While Inward Only treatments reduced spray drift relative to the conventional application method, poorer control of NOW, the key insect pest of almonds, in the Inward Only treatment would likely limit its voluntary use by growers. However, GUTD holds promise for use at the hull split treatment timing to address spray drift. (c) 2016 Society of Chemical Industry. PMID- 27001708 TI - Cellular internalization of LiNbO3 nanocrystals for second harmonic imaging and the effects on stem cell differentiation. AB - Second harmonic generation (SHG) nanocrystals have recently been reported to label cancer cells and other functional cell lines due to their unique double frequency property. In this paper, we report for the first time the use of lithium niobate (LiNbO3, LN) nanocrystals as SHG labels for imaging stem cells. Rat mesenchymal stem cells (rMSCs) were labeled with LN nanocrystals in order to study the cellular internalization of the nanocrystals and the influence on stem cell differentiation. The results showed that LN nanocrystals were endocytosed by the rMSCs and the distribution of the internalized nanoparticles demonstrated a high consistency with the orientation of the actin filaments. Besides, LN-labeled rMSCs showed a concentration-dependent viability. Most importantly, rMSCs labeled with 50 MUg per mL of LN nanocrystals retained their ability to differentiate into both osteogenic and adipogenic lineages. The results prove that LN nanocrystals can be used as a cytocompatible, near-infrared (NIR) light driven cell label for long-term imaging, without hindering stem cell differentiation. This work will promote the use of LN nanocrystals to broader applications like deep-tissue tracking, remote drug delivery and stem cell therapy. PMID- 27001709 TI - Hybrid particle-field molecular dynamics simulation for polyelectrolyte systems. AB - To achieve simulations on large spatial and temporal scales with high molecular chemical specificity, a hybrid particle-field method was proposed recently. This method is developed by combining molecular dynamics and self-consistent field theory (MD-SCF). The MD-SCF method has been validated by successfully predicting the experimentally observable properties of several systems. Here we propose an efficient scheme for the inclusion of electrostatic interactions in the MD-SCF framework. In this scheme, charged molecules are interacting with the external fields that are self-consistently determined from the charge densities. This method is validated by comparing the structural properties of polyelectrolytes in solution obtained from the MD-SCF and particle-based simulations. Moreover, taking PMMA-b-PEO and LiCF3SO3 as examples, the enhancement of immiscibility between the ion-dissolving block and the inert block by doping lithium salts into the copolymer is examined by using the MD-SCF method. By employing GPU acceleration, the high performance of the MD-SCF method with explicit treatment of electrostatics facilitates the simulation study of many problems involving polyelectrolytes. PMID- 27001710 TI - Effect of extremely low-frequency electromagnetic fields on antioxidant activity in the human keratinocyte cell line NCTC 2544. AB - Some epidemiological studies have suggested possible associations between exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) and various diseases. Recently, ELF-EMF has been considered as a therapeutic agent. To support ELF-EMF use in regenerative medicine, in particular in the treatment of skin injuries, we investigated whether significant cell damage occurs after ELF EMF exposure. Reactive oxygen species (ROS) production was evaluated in the human keratinocyte exposed for 1 H to 50 Hz ELF-EMF in a range of field strengths from 0.25 to 2 G. Significant ROS increases resulted at 0.5 and 1 G and under these flux densities ROS production, glutathione content, antioxidant defense activity, and lipid peroxidation markers were assessed for different lengths of time. Analyzed parameters of antioxidant defense and membrane integrity showed a different trend at two selected magnetic fluxes, with a greater sensitivity of the cells exposed to 0.5 G, especially after 1 H. All significant alterations observed in the first 4 H of exposure reverted to controls 24 H after suggesting that under these conditions, ELF-EMF induces a slight oxidative stress that does not overwhelm the metabolic capacity of the cells or have a cytotoxic effect. PMID- 27001711 TI - Evaluation of Audiometric Thresholds and Speech Perception Sentence Test in Adults and Elderly After Cochlear Implantation. AB - AIM: To compare the audiometric thresholds and speech perception sentence test, between two groups with bilateral post-lingual, severe to profound sensorineural hearing loss. METHODS: Retrospective and analytical study, with 59 patients divided into 2 groups (under 60 years and above 60 years old) implanted between May/2002 and February/2007. RESULTS: The first group (control) included 30 patients with a mean age of 44 years. The audiometric threshold value in this group was 26 dB, and the average value of speech perception test was 94%. The second group included 29 patients with a mean age of 69 years. The average audiometric threshold was 29 dB, and the average value of SPT was 90%. The Mann Whitney U-test was considered significant (P<0.05) only for 6-8 KHz frequencies and for SPT. CONCLUSION: Both groups had excellent outcomes in audiometric and speech testing with the use of CI, but with a significantly better performance in the adult group. PMID- 27001712 TI - Heterotrophic Proteobacteria in the vicinity of diffuse hydrothermal venting. AB - Deep-sea hydrothermal vents are highly dynamic habitats characterized by steep temperature and chemical gradients. The oxidation of reduced compounds dissolved in the venting fluids fuels primary production providing the basis for extensive life. Until recently studies of microbial vent communities have focused primarily on chemolithoautotrophic organisms. In our study, we targeted the change of microbial community compositions along mixing gradients, focusing on distribution and capabilities of heterotrophic microorganisms. Samples were retrieved from different venting areas within the Menez Gwen hydrothermal field, taken along mixing gradients, including diffuse fluid discharge points, their immediate surroundings and the buoyant parts of hydrothermal plumes. High throughput 16S rRNA gene amplicon sequencing, fluorescence in situ hybridization, and targeted metagenome analysis were combined with geochemical analyses. Close to diffuse venting orifices dominated by chemolithoautotrophic Epsilonproteobacteria, in areas where environmental conditions still supported chemolithoautotrophic processes, we detected microbial communities enriched for versatile heterotrophic Alpha- and Gammaproteobacteria. The potential for alkane degradation could be shown for several genera and yet uncultured clades. We propose that hotspots of chemolithoautotrophic life support a 'belt' of heterotrophic bacteria significantly different from the dominating oligotrophic microbiota of the deep sea. PMID- 27001713 TI - Occurrence of alkylphenols and bisphenol A in wild mussel samples from the Spanish Atlantic coast and Bay of Biscay. AB - Wild mussels (Mytilus galloprovincialis) were selected as bioindicators of chemical pollution to evaluate the occurrence and spatial distribution of five endocrine disrupting compounds in the Spanish Atlantic coast and Bay of Biscay. A total of 24 samples were collected in May, 2011 and analysed by selective pressurized liquid extraction followed by liquid chromatography tandem mass spectrometry determination. Branched alkylphenols (4-tert-octylphenol and nonylphenol) were determined in more than 90% of the analysed samples whereas the presence of linear alkylphenols (4-n-octylphenol and 4-n-nonylphenol) was scarcely detected (<12% of the samples). Wastewater treatment plants discharges and nautical, fishing and shipping activities were considered the primary sources of contamination by alkylphenols. Bisphenol A was found in 16% of the analysed samples associated to punctual industrial discharges. A total endocrine disrupting compound (alkylphenols and bisphenol A) average concentration of 604ngg(-1) dw was calculated and nonylphenol was the main contributor in almost all sampling points. PMID- 27001714 TI - Effects of temperature and nutrients on changes in genetic diversity of bacterioplankton communities in a semi-closed bay, South Korea. AB - Bacterioplankton communities in a semi-closed bay (Jangmok Bay, South Korea) were analysed using a 16S rDNA multiplex 454 pyrosequencing approach. Diversity and operational taxonomic units of bacterioplankton communities in the Jangmok Bay are highest in cold water seasons and lowest in warm water ones. During cold seasons, alpha-proteobacteria respond rapidly to pulses of the concentration of inorganic nutrients, while gamma-proteobacteria during warm water seasons are the most active type of bacterioplankton resent in the prevailing conditions, which include high dissolved organic carbon, chemical oxygen demand and primary production. Cyanobacteria, a minor group constituting 4.58% of the total bacterioplankton, are more abundant at low temperature. Flavobacteria are more abundant in nutrient-rich conditions and the abundance of this group also demonstrated a delayed decline following summer phytoplankton blooms. The pronounced seasonal oscillations in phosphorus concentration and temperature exert strong selection pressure on bacterioplankton communities. PMID- 27001715 TI - Transcriptomic response to water accommodated fraction of crude oil exposure in the gill of Japanese flounder, Paralichthys olivaceus. AB - Illumina-based RNA-seq was used to determine the short-term transcriptomic responses of Paralichthys olivaceus gill to an environmentally relevant level of water accommodated fraction (WAF) of crude oil. 213,979 transcripts and 128,482 unigenes were obtained. Differential expression analysis revealed that 1641 and 2142 genes were significantly up- and down-regulated. Enrichment analysis identified a set of GO terms and putative pathways involved in the response of P. olivaceus to WAF exposure. Analysis of the transcripts revealed the effective protective mechanisms of P. olivaceus to reduce the toxic effects of WAF. Moreover, WAF exposure induced the metabolism of energy substrates, and downstream pathway genes were modified to provide protection against toxic damage. Transcripts analysis demonstrated that the genes involved in circadian rhythm signaling were regulated in gills of P. olivaceus exposed to WAF. These results provide insights into the mechanisms of WAF-induced toxicity in fishes and into the WAF-sensitive biomarkers in P. olivaceus. PMID- 27001716 TI - Spatial assessment and source identification of heavy metals pollution in surface water using several chemometric techniques. AB - This study presents the determination of the spatial variation and source identification of heavy metal pollution in surface water along the Straits of Malacca using several chemometric techniques. Clustering and discrimination of heavy metal compounds in surface water into two groups (northern and southern regions) are observed according to level of concentrations via the application of chemometric techniques. Principal component analysis (PCA) demonstrates that Cu and Cr dominate the source apportionment in northern region with a total variance of 57.62% and is identified with mining and shipping activities. These are the major contamination contributors in the Straits. Land-based pollution originating from vehicular emission with a total variance of 59.43% is attributed to the high level of Pb concentration in the southern region. The results revealed that one state representing each cluster (northern and southern regions) is significant as the main location for investigating heavy metal concentration in the Straits of Malacca which would save monitoring cost and time. CAPSULE: The monitoring of spatial variation and source of heavy metals pollution at the northern and southern regions of the Straits of Malacca, Malaysia, using chemometric analysis. PMID- 27001718 TI - Odor-Specific Loss of Smell Sensitivity with Age as Revealed by the Specific Sensitivity Test. AB - The perception of odor mixtures plays an important role in human food intake, behavior, and emotions. Decline of smell acuity with normal aging could impact food perception and preferences at various ages. However, since the landmark Smell Survey by National Geographic, little has been elucidated on differences in the onset and extent of loss in olfactory sensitivity toward single odorants. Here, using the Specific Sensitivity test, we show the onset and extent of loss in both identification and detection thresholds of odorants with age are odorant specific. Subjects of Chinese descent in Singapore (186 women, 95 men), aged 21 80 years, were assessed for olfactory sensitivity of 10 odorants from various odor groups. Notably, subjects in their 70s required 179 times concentration of rose-like odorant (2-phenylethanol) than subjects in the 20s, while thresholds for onion-like 2-methyloxolane-3-thiol only differed by 3 times between the age groups. In addition, identification rate for 2-phenylethanol was negatively correlated with age throughout adult life whereas mushroom-like oct-1-en-3-ol was equally identified by subjects across all ages. Our results demonstrated the girth of differentiated olfactory loss due to normal ageing, which potentially affect overall perception and preferences of odor mixtures with age. PMID- 27001717 TI - Development of a short-term chronic toxicity test with a tropical mysid. AB - There is an increasing need to develop reliable methodologies for chronic toxicity testing using tropical species. The present work aimed at developing a suitable short-term chronic toxicity test with Mysidopsis juniae using zinc (Zn) and nickel (Ni) as model chemicals and growth (length and dry weight), survival, and egg production (number of females with eggs) as endpoints after seven days of exposure. Survival and growth of newborn M. juniae were affected by chronic exposure to zinc, while nickel affected only survival. For zinc, dry weight was the most sensitive endpoint with significant effects even at the lowest tested concentration (75MUgZn.L(-1)), whereas for nickel, survival was the most sensitive parameter (LC20 of 26MUgNi.L(-1)). Egg production was not affected. M. juniae short-term chronic testing is a sensitive approach to evaluating metal toxicity; further studies are necessary to assess chronic toxicity for others contaminants in the proposed assay. PMID- 27001719 TI - Another four bricks in the wall. PMID- 27001720 TI - Changing chemistry by degrees. PMID- 27001721 TI - Synthetic biology: Tailor-made genetic codes. PMID- 27001722 TI - Oxide interfaces: Mismatched lattices patched up. PMID- 27001723 TI - Metal-organic frameworks: A thin film opening. PMID- 27001724 TI - Click chemistry: Straining to react. PMID- 27001725 TI - Substrate channelling as an approach to cascade reactions. AB - Millions of years of evolution have produced biological systems capable of efficient one-pot multi-step catalysis. The underlying mechanisms that facilitate these reaction processes are increasingly providing inspiration in synthetic chemistry. Substrate channelling, where intermediates between enzymatic steps are not in equilibrium with the bulk solution, enables increased efficiencies and yields in reaction and diffusion processes. Here, we review different mechanisms of substrate channelling found in nature and provide an overview of the analytical methods used to quantify these effects. The incorporation of substrate channelling into synthetic cascades is a rapidly developing concept, and recent examples of the fabrication of cascades with controlled diffusion and flux of intermediates are presented. PMID- 27001726 TI - Expanding the amino acid repertoire of ribosomal polypeptide synthesis via the artificial division of codon boxes. AB - In ribosomal polypeptide synthesis the library of amino acid building blocks is limited by the manner in which codons are used. Of the proteinogenic amino acids, 18 are coded for by multiple codons and therefore many of the 61 sense codons can be considered redundant. Here we report a method to reduce the redundancy of codons by artificially dividing codon boxes to create vacant codons that can then be reassigned to non-proteinogenic amino acids and thereby expand the library of genetically encoded amino acids. To achieve this, we reconstituted a cell-free translation system with 32 in vitro transcripts of transfer RNASNN (tRNASNN) (S = G or C), assigning the initiator and 20 elongator amino acids. Reassignment of three redundant codons was achieved by replacing redundant tRNASNNs with tRNASNNs pre-charged with non-proteinogenic amino acids. As a demonstration, we expressed a 32-mer linear peptide that consists of 20 proteinogenic and three non proteinogenic amino acids, and a 14-mer macrocyclic peptide that contains more than four non-proteinogenic amino acids. PMID- 27001727 TI - Microscopic origin of chiral shape induction in achiral crystals. AB - In biomineralization, inorganic materials are formed with remarkable control of the shape and morphology. Chirality, as present in the biomolecular world, is therefore also common for biominerals. Biomacromolecules, like proteins and polysaccharides, are in direct contact with the mineral phase and act as modifiers during nucleation and crystal growth. Owing to their homochirality- they exist only as one of two possible mirror-symmetric isomers--their handedness is often transferred into the macroscopic shape of the biomineral crystals, but the way in which handedness is transmitted into achiral materials is not yet understood at the atomic level. By using the submolecular resolution capability of scanning tunnelling microscopy, supported by photoelectron diffraction and density functional theory, we show how the chiral 'buckybowl' hemibuckminsterfullerene arranges copper surface atoms in its vicinity into a chiral morphology. We anticipate that such new insight will find its way into materials synthesis techniques. PMID- 27001728 TI - Effects of correlated parameters and uncertainty in electronic-structure-based chemical kinetic modelling. AB - Kinetic models based on first principles are becoming common place in heterogeneous catalysis because of their ability to interpret experimental data, identify the rate-controlling step, guide experiments and predict novel materials. To overcome the tremendous computational cost of estimating parameters of complex networks on metal catalysts, approximate quantum mechanical calculations are employed that render models potentially inaccurate. Here, by introducing correlative global sensitivity analysis and uncertainty quantification, we show that neglecting correlations in the energies of species and reactions can lead to an incorrect identification of influential parameters and key reaction intermediates and reactions. We rationalize why models often underpredict reaction rates and show that, despite the uncertainty being large, the method can, in conjunction with experimental data, identify influential missing reaction pathways and provide insights into the catalyst active site and the kinetic reliability of a model. The method is demonstrated in ethanol steam reforming for hydrogen production for fuel cells. PMID- 27001730 TI - Interface control by chemical and dimensional matching in an oxide heterostructure. AB - Interfaces between different materials underpin both new scientific phenomena, such as the emergent behaviour at oxide interfaces, and key technologies, such as that of the transistor. Control of the interfaces between materials with the same crystal structures but different chemical compositions is possible in many materials classes, but less progress has been made for oxide materials with different crystal structures. We show that dynamical self-organization during growth can create a coherent interface between the perovskite and fluorite oxide structures, which are based on different structural motifs, if an appropriate choice of cations is made to enable this restructuring. The integration of calculation with experimental observation reveals that the interface differs from both the bulk components and identifies the chemical bonding requirements to connect distinct oxide structures. PMID- 27001729 TI - Modular synthesis of N-glycans and arrays for the hetero-ligand binding analysis of HIV antibodies. AB - A new class of broadly neutralizing antibodies (bNAbs) from HIV donors has been reported to target the glycans on gp120--a glycoprotein found on the surface of the virus envelope--thus renewing hope of developing carbohydrate-based HIV vaccines. However, the version of gp120 used in previous studies was not from human T cells and so the glycosylation pattern could be somewhat different to that found in the native system. Moreover, some antibodies recognized two different glycans simultaneously and this cannot be detected with the commonly used glycan microarrays on glass slides. Here, we have developed a glycan microarray on an aluminium-oxide-coated glass slide containing a diverse set of glycans, including homo- and mixed N-glycans (high-mannose, hybrid and complex types) that were prepared by modular chemo-enzymatic methods to detect the presence of hetero-glycan binding behaviours. This new approach allows rapid screening and identification of optimal glycans recognized by neutralizing antibodies, and could speed up the development of HIV-1 vaccines targeting cell surface glycans. PMID- 27001732 TI - Iterative reactions of transient boronic acids enable sequential C-C bond formation. AB - The ability to form multiple carbon-carbon bonds in a controlled sequence and thus rapidly build molecular complexity in an iterative fashion is an important goal in modern chemical synthesis. In recent times, transition-metal-catalysed coupling reactions have dominated in the development of C-C bond forming processes. A desire to reduce the reliance on precious metals and a need to obtain products with very low levels of metal impurities has brought a renewed focus on metal-free coupling processes. Here, we report the in situ preparation of reactive allylic and benzylic boronic acids, obtained by reacting flow generated diazo compounds with boronic acids, and their application in controlled iterative C-C bond forming reactions is described. Thus far we have shown the formation of up to three C-C bonds in a sequence including the final trapping of a reactive boronic acid species with an aldehyde to generate a range of new chemical structures. PMID- 27001731 TI - Designed metalloprotein stabilizes a semiquinone radical. AB - Enzymes use binding energy to stabilize their substrates in high-energy states that are otherwise inaccessible at ambient temperature. Here we show that a de novo designed Zn(II) metalloprotein stabilizes a chemically reactive organic radical that is otherwise unstable in aqueous media. The protein binds tightly to and stabilizes the radical semiquinone form of 3,5-di-tert-butylcatechol. Solution NMR spectroscopy in conjunction with molecular dynamics simulations show that the substrate binds in the active site pocket where it is stabilized by metal-ligand interactions as well as by burial of its hydrophobic groups. Spectrochemical redox titrations show that the protein stabilized the semiquinone by reducing the electrochemical midpoint potential for its formation via the one electron oxidation of the catechol by approximately 400 mV (9 kcal mol(-1)). Therefore, the inherent chemical properties of the radical were changed drastically by harnessing its binding energy to the metalloprotein. This model sets the basis for designed enzymes with radical cofactors to tackle challenging chemistry. PMID- 27001733 TI - Reprogramming the assembly of unmodified DNA with a small molecule. AB - The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA 'alphabet' by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces, reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid (PNA) all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials. PMID- 27001734 TI - Crystalline coordination framework endowed with dynamic gate-opening behaviour by being downsized to a thin film. AB - The fabrication of porous coordination frameworks in thin-film forms has been investigated intensively with a view to using their structural response to external stimuli and guests for potential nanotechnological applications, for example as membranes for gas separation. Here we report a coordination framework that exhibits a dynamic guest-sorption behaviour in a nanometre-sized thin-film form (16 nm thick), yet shows no guest uptake in the bulk. Highly oriented crystalline thin films of this coordination framework--which consists of interdigitated two-dimensional layers of {Fe(py)2[Pt(CN)4]} (py, pyridine)--were fabricated through liquid-phase layer-by-layer synthesis. The resulting thin film exhibited a clear guest uptake with a structural transformation of the gate opening type as characterized by in situ X-ray diffraction. Increasing the film's thickness markedly suppressed this behaviour. We envisage that such a crystal downsizing effect may be observed with other coordination frameworks, and may be of use to develop functional materials, for example, for switching or sensing devices. PMID- 27001735 TI - Chemical amplification of magnetic field effects relevant to avian magnetoreception. AB - Magnetic fields as weak as the Earth's can change the yields of radical pair reactions even though the energies involved are orders of magnitude smaller than the thermal energy, kBT, at room temperature. Proposed as the source of the light dependent magnetic compass in migratory birds, the radical pair mechanism is thought to operate in cryptochrome flavoproteins in the retina. Here we demonstrate that the primary magnetic field effect on flavin photoreactions can be amplified chemically by slow radical termination reactions under conditions of continuous photoexcitation. The nature and origin of the amplification are revealed by studies of the intermolecular flavin-tryptophan and flavin-ascorbic acid photocycles and the closely related intramolecular flavin-tryptophan radical pair in cryptochrome. Amplification factors of up to 5.6 were observed for magnetic fields weaker than 1 mT. Substantial chemical amplification could have a significant impact on the viability of a cryptochrome-based magnetic compass sensor. PMID- 27001736 TI - Iridium's impact. PMID- 27001737 TI - How free are Canada's unmuzzled scientists? PMID- 27001738 TI - Nunavut's new suicide prevention strategy. PMID- 27001740 TI - Ethical qualms about genetic prognosis. PMID- 27001739 TI - Comparative effectiveness of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers in patients with type 2 diabetes and retinopathy. AB - BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective treatments for diabetic retinopathy, but randomized trials and meta-analyses comparing their effects on macrovascular complications have yielded conflicting results. We compared the effectiveness of these drugs in patients with pre-existing diabetic retinopathy in a large population-based cohort. METHODS: We conducted a propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. We included adult patients prescribed an ACE inhibitor or ARB within 90 days after diagnosis of diabetic retinopathy between 2000 and 2010. Primary outcomes were all-cause death and major adverse cardiovascular events (myocardial infarction, ischemic stroke or cardiovascular death). Secondary outcomes were hospital admissions with acute kidney injury or hyperkalemia. RESULTS: We identified 11 246 patients receiving ACE inhibitors and 15 173 receiving ARBs, of whom 9769 patients in each group were matched successfully by propensity scores. In the intention-to-treat analyses, ARBs were similar to ACE inhibitors in risk of all-cause death (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.87-1.01) and major adverse cardiovascular events (HR 0.95, 95% CI 0.87-1.04), including myocardial infarction (HR 1.03, 95% CI 0.88-1.20), ischemic stroke (HR 0.94, 95% CI 0.85 1.04) and cardiovascular death (HR 1.01, 95% CI 0.88-1.16). They also did not differ from ACE inhibitors in risk of hospital admission with acute kidney injury (HR 1.01, 95% CI 0.91-1.13) and hospital admission with hyperkalemia (HR 1.01, 95% CI 0.86-1.18). Results were similar in as-treated analyses. INTERPRETATION: Our study showed that ACE inhibitors were similar to ARBs in risk of all-cause death, major adverse cardiovascular events and adverse effects among patients with pre-existing diabetic retinopathy. PMID- 27001741 TI - Zika virus and microcephaly. PMID- 27001742 TI - Decriminalize payment of donors and surrogates, says MP. PMID- 27001743 TI - Diaphragmatic stimulation caused by cardiac resynchronization treatment. PMID- 27001744 TI - Epidemiology of laboratory confirmed measles virus cases in Amhara Regional State of Ethiopia, 2004-2014. AB - BACKGROUND: Measles is a highly contagious viral infection causing large outbreaks all over the world. Despite the availability of safe and cost effective vaccine, measles remained endemic with persistent periodic outbreaks in the Horn of Africa. The aim of this study is to characterize laboratory confirmed measles cases in Amhara Regional State, which was one of the highly affected regions in Ethiopia. METHOD: A suspected measles case was defined as any person presenting with fever, maculopapular rash and one or more of the three symptoms cough, coryza or conjunctivitis or a patient in whom a clinician suspects measles. A blood sample was collected for any measles suspected patient with a case based investigation form and specimen transported to the National Measles Laboratory in good condition where it was to be tested for Measles IgM antibody by ELISA technique. Data was entered and analyzed using Epi-Info 3.5.4 software. RESULT: A total of 6579 samples were tested for measles IgM among 7296 samples collected in Amhara Regional State over 11 years (2004-2014). Of the tested samples, 2412 (36.7%) were found positive, while 3965 and 202 samples were found to be negative and equivocal (compatible) respectively. Patients with age >= 10 years were the most affected. The highest number of laboratory confirmed measles cases were detected in 2014 and cases were occurred in all of the 11 zones of the state. A seasonal peak was noted in the hot-dry season of the year. CONCLUSION: Measles remains to be a public health problem in Amhara Regional State of Ethiopia, mostly affecting people >= 10 years of age. Measles virus was detected in all zones of the state, reaching its peak in the hot-dry season. To reduce the incidence of measles, it is highly recommended to improve routine immunization, and conduct a wide age group campaign. Additional research to evaluate the knowledge, attitudes and practices of the general population and health care professionals about measles infection and vaccination is important. Genotyping of circulating measles virus strain is recommended. PMID- 27001745 TI - Microfluidic Manipulation of Core/Shell Nanoparticles for Oral Delivery of Chemotherapeutics: A New Treatment Approach for Colorectal Cancer. AB - A microfluidics approach to synthesize core-shell nanocarriers with high pH tunability is described. The sacrificial shell protects the core layer with the drugs and prevents their release in the severe pH conditions of the gastrointestinal tract, while allowing for drug release in the proximity of a tumor. The proposed nanoparticulate drug-delivery system is designed for the oral administration of cancer therapeutics. PMID- 27001746 TI - Probing the effects of the ester functional group, alkyl side chain length and anions on the bulk nanostructure of ionic liquids: a computational study. AB - The effects of ester addition on nanostructural properties of biodegradable ILs composed of 1-alkoxycarbonyl-3-alkyl-imidazolium cations ([C1COOCnC1im](+), n = 1, 2, 4) combined with [Br](-), [NO3](-), [BF4](-), [PF6](-), [TfO](-), and [Tf2N](-) were explored by using the molecular dynamics (MD) simulations and quantum theory of atoms in molecules (QTAIM) analysis at 400 K. Various thermodynamic properties of these ILs were extensively computed in our earlier work (Ind. Eng. Chem. Res., 2015, 54, 11678-11700). Nano-scale segregation analysis demonstrates the formation of a small spherical island-like hydrocarbon within the continuous ionic domain for ILs with short alkyl side chain ([C1COOC1C1im]), and a sponge-like nanostructure for the compound with long alkyl side chain ([C1COOC4C1im]). Ester-functionalized ILs with ethyl side chain ([C1COOC2C1im]) are the turning point between two different morphologies. Non polar channels were observed for [C1COOC4C1im] ILs composed of smaller anions such as [Br] and [NO3], whereas clustering organization was found for the other anions. Formation of the spherical micelle-like nanostructure was seen for lengthened cations. Finally, the incorporation of an ester group into the alkyl side chain of the cation leads to stronger segregation between charged and uncharged networks, which consequently increased the possibility of self-assembly and micelle formation. PMID- 27001747 TI - The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation. AB - IRF8 and IRF1 are transcriptional regulators that play critical roles in the development and function of myeloid cells, including activation of macrophages by proinflammatory signals such as interferon-gamma (IFN-gamma). Loss of IRF8 or IRF1 function causes severe susceptibility to infections in mice and in humans. We used chromatin immunoprecipitation sequencing and RNA sequencing in wild type and inIRF8andIRF1mutant primary macrophages to systematically catalog all of the genes bound by (cistromes) and transcriptionally activated by (regulomes) IRF8, IRF1, PU.1, and STAT1, including modulation of epigenetic histone marks. Of the seven binding combinations identified, two (cluster 1 [IRF8/IRF1/STAT1/PU.1] and cluster 5 [IRF1/STAT1/PU.1]) were found to have a major role in controlling macrophage transcriptional programs both at the basal level and after IFN-gamma activation. They direct the expression of a set of genes, the IRF8/IRF1 regulome, that play critical roles in host inflammatory and antimicrobial defenses in mouse models of neuroinflammation and of pulmonary tuberculosis, respectively. In addition, this IRF8/IRF1 regulome is enriched for genes mutated in human primary immunodeficiencies and with loci associated with several inflammatory diseases in humans. PMID- 27001750 TI - First Genome-Wide Mutational Map of Macaques a Boon for Evolutionary Studies. PMID- 27001748 TI - Absence of MHC class II on cDCs results in microbial-dependent intestinal inflammation. AB - Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative importance in maintaining immune homeostasis is poorly understood. To examine the significance of cDC-initiated adaptive immunity in maintaining homeostasis, independent of their innate activities, we generated a cDC-specific Cre mouse and crossed it to a floxed MHC class II (MHCII) mouse. Absence of MHCII on cDCs resulted in chronic intestinal inflammation that was alleviated by antibiotic treatment and entirely averted under germ-free conditions. Uncoupling innate and adaptive functions of cDCs revealed that innate immune functions of cDCs are insufficient to maintain homeostasis and antigen presentation by cDCs is essential for a mutualistic relationship between the host and intestinal bacteria. PMID- 27001749 TI - Conditional deletion of L1CAM in human neurons impairs both axonal and dendritic arborization and action potential generation. AB - Hundreds of L1CAM gene mutations have been shown to be associated with congenital hydrocephalus, severe intellectual disability, aphasia, and motor symptoms. How such mutations impair neuronal function, however, remains unclear. Here, we generated human embryonic stem (ES) cells carrying a conditional L1CAM loss-of function mutation and produced precisely matching control and L1CAM-deficient neurons from these ES cells. In analyzing two independent conditionally mutant ES cell clones, we found that deletion of L1CAM dramatically impaired axonal elongation and, to a lesser extent, dendritic arborization. Unexpectedly, we also detected an ~20-50% and ~20-30% decrease, respectively, in the levels of ankyrinG and ankyrinB protein, and observed that the size and intensity of ankyrinG staining in the axon initial segment was significantly reduced. Overexpression of wild-type L1CAM, but not of the L1CAM point mutants R1166X and S1224L, rescued the decrease in ankyrin levels. Importantly, we found that the L1CAM mutation selectively decreased activity-dependent Na(+)-currents, altered neuronal excitability, and caused impairments in action potential (AP) generation. Thus, our results suggest that the clinical presentations of L1CAM mutations in human patients could be accounted for, at least in part, by cell-autonomous changes in the functional development of neurons, such that neurons are unable to develop normal axons and dendrites and to generate normal APs. PMID- 27001751 TI - Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity-[(11) C]MP4A PET study. PMID- 27001752 TI - Inspired by nonenveloped viruses escaping from endo-lysosomes: a pH-sensitive polyurethane micelle for effective intracellular trafficking. AB - A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core exposure, resulting from the detachment of the hydrophilic polyethylene glycol (PEG) shell, are similar to the behavior of a nonenveloped virus when trapped in acidic endo lysosomes. Moreover, the degradation mechanism was verified by gel permeation chromatography (GPC). The endo-lysosomal membrane rupture induced by these transformed micelles is clearly observed by transmission electron microscopy. Consequently, excellent antitumor activity is confirmed both in vitro and in vivo. The results verify that the pHPM could be a promising new drug delivery tool for the treatment of cancer and other diseases. PMID- 27001753 TI - Predictors of opportunistic illnesses incidence in post combination antiretroviral therapy era in an urban cohort from Rio de Janeiro, Brazil. AB - BACKGROUND: Opportunistic illnesses still account for a huge proportion of hospitalizations and deaths among HIV-infected patients in the post combination antiretroviral therapy (cART) era, particularly in middle- and low-income countries. The aim of this study was to assess predictors of the top four most incident opportunistic illnesses (tuberculosis, esophageal candidiasis, cerebral toxoplasmosis and Pneumocystis jiroveci pneumonia) in an HIV clinical cohort from a middle-income country in the post cART era. METHODS: A total of 2835 HIV infected participants aged >= 18 years at enrollment were followed from January 2000 to December 2012 until the occurrence of their first opportunistic illness, death or end of study, whichever occurred first. Extended Cox proportional hazards regression models, stratified by use of cART, were fitted to assess predictors of opportunistic illness incidence during follow-up. RESULTS: The incidence rates of tuberculosis, esophageal candidiasis, cerebral toxoplasmosis and Pneumocystis jiroveci pneumonia were 15.3, 8.6, 6.0, 4.8 per 1000 persons year, respectively. Disease specific adjusted Cox models showed that presence of an opportunistic illness at enrollment significantly increased disease incidence while higher nadir CD4+ T lymphocyte count had a significant protective effect in patients not in use of cART. Duration of cART use also significantly reduced disease incidence. CONCLUSIONS: Our findings show that, still in the post-cART era, prevention of opportunistic infections can be achieved by preventing immune deterioration by instituting early use of cART. Interventions focusing on early diagnosis and linkage to care in addition to the prompt initiation of cART are essential to reduce the incidence of opportunistic illnesses among HIV infected patients in post-cART era. PMID- 27001754 TI - Serological Evidence of Infection with Endemic Human Pathogens Among Free-Ranging Old World Monkeys in Puerto Rico. AB - Serum specimens from free-ranging but nonnative patas monkeys (Erythrocebus patas) and rhesus macaques (Macaca mulatta) in southwestern Puerto Rico (PR) were tested for antibodies to infection with dengue viruses (DENVs), West Nile virus (WNV), Leptospira species, and Burkholderia pseudomallei by microneutralization, plaque reduction neutralization, microscopic agglutination, and indirect hemagglutination, respectively. Of 23 animals (21 E. patas and two M. mulatta) tested, all had evidence of prior DENV infection, and of 17 animals tested for WNV, nine (53%) had evidence of prior infection. Of 24 (22 E. patas, two M. mulatta) tested for Leptospira spp., 10 (42%) had evidence of prior exposure, and one patas monkey had antibodies against B. pseudomallei The acquisition of pathogens endemic among humans in PR by resident nonhuman primates merits further study to define modes of acquisition. PMID- 27001755 TI - Habitat Partitioning of Malaria Vectors in Nchelenge District, Zambia. AB - Nchelenge District in Luapula Province, northern Zambia, experiences holoendemic malaria despite implementation of vector control programs. The major Anopheles vectors that contribute to Plasmodium falciparum transmission in this area had not previously been well defined. Three collections performed during the 2012 wet and dry seasons and the 2013 wet season revealed Anopheles funestus sensu stricto and Anopheles gambiae sensu stricto as the main vectors, where 80-85% of each collection was composed of An. funestus Both vectors were found to be highly anthropophilic, and An. funestus has higher sporozoite infection rates (SIRs) and entomological inoculation rates (EIRs) year-round compared with An. gambiae: SIRs of 1.8-3.0% and 0-2.5%, respectively, and EIRs of 3.7-41.5 infectious bites per 6 month period (ib/p/6mo) and 0-5.9 ib/p/6mo, respectively. Spatial and temporal changes in each vector's dynamics and bionomics were also observed. Anopheles funestus was the predominant vector in the villages near Kenani Stream in both wet and dry seasons, whereas An. gambiae was found to be the main vector in areas near Lake Mweru during the wet season. The vector data illustrate the need for broader temporal and spatial sampling in Nchelenge and present unique opportunities to further our understanding of malarial transmission and implications for malarial control in high-risk areas. PMID- 27001756 TI - A Case of Fatal Serotonin Syndrome-Like Human Rabies Caused by Tricolored Bat Associated Rabies Virus. AB - Human rabies is a fatal disease, transmitted by saliva of infected animals, and the diagnosis requires a high index of suspicion. Very few cases are reported annually in the United States. We present a case of human rabies without a clear exposure history that masqueraded as serotonin syndrome. PMID- 27001757 TI - Hepatitis B Vaccination Coverage and Prevalence of Hepatitis B Surface Antigen Among Children in French Polynesia, 2014. AB - French Polynesia is considered to be moderately endemic for chronic hepatitis B virus infection, with an estimated 3% of the population having hepatitis B surface antigen (HBsAg). From 1990 to 1992, a 3-dose hepatitis B vaccination series was introduced into the routine infant immunization schedule in French Polynesia, including a birth dose (BD). In 2014, a nationally representative 2 stage cluster survey was undertaken to evaluate the impact of the vaccination program on HBsAg prevalence among school children (~6 years of age) in Cours Preparatoire (CP). Documented vaccination data were reviewed for all eligible children; children with consent were tested for HBsAg with a rapid point-of-care test. In total, 1,660 students were identified; 1,567 (94%) had vaccination data for review and 1,196 (72%) participated in the serosurvey. Three-dose vaccination coverage was 98%, while timely BD coverage, defined as a dose administered within 24 hours of life, was 89%. Receipt of the second and third doses was often delayed, with 75% and 55% receiving a second and third dose within 1 month of the recommended age, respectively. No children tested positive for HBsAg. French Polynesia's vaccination program has achieved high coverage and an HBsAg seroprevalence of 0% (0-0.5%) among CP school children, but timeliness of vaccination could be improved. PMID- 27001758 TI - Integrating Water Treatment into Antenatal Care: Impact on Use of Maternal Health Services and Household Water Treatment by Mothers-Rural Uganda, 2013. AB - To increase maternal health service use and household water treatment (HWT), free water treatment kits were provided at first antenatal care (ANC) visits and free water treatment sachet refills were provided at follow-up ANC visits, delivery, and postnatal visits in 46 health facilities in rural Uganda. We evaluated the impact by surveying 226 women in the initiative (intervention group) and 207 women who received ANC before the initiative began (comparison group). There was no differences in the percentages of intervention and comparison group women with >= 4 ANC visits; however, a higher percentage of intervention group women reported treating their drinking water (31.7% versus 19.7%, P = 0.01), and had free chlorine residual in stored water (13.5% versus 3.4%, P = 0.02) than comparison group women. The intervention did not appear to motivate increased maternal health service use, but demonstrated improvements in HWT. PMID- 27001759 TI - Investigation of Recurrent Melioidosis in Lao People's Democratic Republic by Multilocus Sequence Typing. AB - Melioidosis is an infectious disease caused by the saprophytic bacterium Burkholderia pseudomallei In northeast Thailand and northern Australia, where the disease is highly endemic, a range of molecular tools have been used to study its epidemiology and pathogenesis. In the Lao People's Democratic Republic (Laos) where melioidosis has been recognized as endemic since 1999, no such studies have been undertaken. We used a multilocus sequence typing scheme specific for B. pseudomallei to investigate nine cases of culture-positive recurrence occurring in 514 patients with melioidosis between 2010 and 2015: four were suspected to be relapses while the other five represented reinfections. In addition, two novel sequence types of the bacterium were identified. The low overall recurrence rates (2.4%) and proportions of relapse and reinfection in the Laos are consistent with those described in the recent literature, reflecting the effective use of appropriate antimicrobial therapy. PMID- 27001760 TI - Analyzing Deoxyribose Nucleic Acid from Malaria Rapid Diagnostic Tests to Study Plasmodium falciparum Genetic Diversity in Mali. AB - We evaluated the use of positive malaria rapid diagnostic tests (mRDTs) to determine genetic diversity of Plasmodium falciparum in Mali. Genetic diversity was assessed via multiple loci variable number of tandem repeats analysis (MLVA). We performed DNA extraction from 104 positive and 30 negative used mRDTs that had been stored at ambient temperature for up to 14 months. Extracted DNA was analyzed via quantitative polymerase chain reaction (qPCR), and MLVA genotyping was then assessed on positive qPCR samples. Eighty-three of the positive mRDTs (83/104, 79.8%) and none of the negative mRDTs were confirmed P. falciparum positive via qPCR. We achieved complete genotyping of 90.4% (75/83) of the qPCR positive samples. Genotyping revealed high genetic diversity among P. falciparum populations in Mali and an absence of population clustering. We show that mRDTs are useful to monitor P. falciparum genetic diversity and thereby can provide essential data to guide malaria control programs. PMID- 27001761 TI - Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission. AB - Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation. PMID- 27001762 TI - The Impact of Prior Flavivirus Infections on the Development of Type 2 Diabetes Among the Indigenous Australians. AB - It is estimated that 5% of Australians over the age of 18 have diabetes, with the number of new cases increasing every year. Type 2 diabetes (T2D) also represents a significant disease burden in the Australian indigenous population, where prevalence is three times greater than that of non-indigenous Australians. Prevalence of T2D has been found to be higher in rural and remote indigenous Australian populations compared with urban indigenous Australian populations. Several studies have also found that body mass index and waist circumference are not appropriate for the prediction of T2D risk in indigenous Australians. Regional and remote areas of Australia are endemic for a variety of mosquito borne flaviviruses. Studies that have investigated seroprevalence of flaviviruses in remote aboriginal communities have found high proportions of seroconversion. The family Flaviviridae comprises several genera of viruses with non-segmented single-stranded positive sense RNA genomes, and includes the flaviviruses and hepaciviruses. Hepatitis C virus (HCV) has been shown to be associated with insulin resistance and subsequent development of T2D. Flaviviruses and HCV possess conserved proteins and subgenomic RNA structures that may play similar roles in the development of insulin resistance. Although dietary and lifestyle factors are associated with increased risk of developing T2D, the impact of infectious diseases such as arboviruses has not been assessed. Flaviviruses circulating in indigenous Australian communities may play a significant role in inducing glucose intolerance and exacerbating T2D. PMID- 27001763 TI - Absence of Association Between Sickle Trait Hemoglobin and Placental Malaria Outcomes. AB - Heterozygous hemoglobin S (HbAS), or sickle trait, protects children from life threatening falciparum malaria, potentially by attenuating binding of Plasmodium infected red blood cells (iRBCs) to extracellular ligands. Such binding is central to the pathogenesis of placental malaria (PM). We hypothesized that HbAS would be associated with reduced risks of PM and low birth weight (LBW). We tested this hypothesis in 850 delivering women in southern Malawi. Parasites were detected by polymerase chain reaction in placental and peripheral blood, and placentae were scored histologically for PM. The prevalence of HbAS was 3.7%, and 11.2% of infants were LBW (< 2,500 g). The prevalence of Plasmodium falciparum was 12.7% in placental and 8.5% in peripheral blood; 24.4% of placentae demonstrated histological evidence of P. falciparum HbAS was not associated with reduced prevalence of P. falciparum in placental (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.50-3.23, P = 0.61) or peripheral blood (OR: 2.53, 95% CI: 1.08-2.54, P = 0.03), prevalence of histological PM (OR: 0.97, 95% CI: 0.40 2.34, P = 0.95), or prevalence of LBW (OR: 0.82, 95% CI: 0.24-2.73, P = 0.74). Mean (standard deviation) birth weights of infants born to HbAS (2,947 g [563]) and, homozygous hemoglobin A (2,991 g [465]) mothers were similar. Across a range of parasitologic, clinical, and histologic outcomes, HbAS did not confer protection from PM or its adverse effects. PMID- 27001764 TI - Geographical Distribution of MDR1 Expression in Leishmania Isolates, from Greece and Cyprus, Measured by the Rhodamine-123 Efflux Potential of the Isolates, Using Flow Cytometry. AB - Leishmaniasis, a neglected vector-borne disease caused by the protozoan parasite Leishmania, is encountered in 98 countries causing serious concerns to public health. The most alarming is the development of parasite drug resistance, a phenomenon increasingly encountered in the field rendering chemotherapy ineffective. Although resistance to drugs is a complex phenomenon, the rate of efflux of the fluorescent dye Rhodamine-123 from the parasite body, using flow cytometry, is an indication of the isolate's ability to efflux the drug, thus avoiding death. The rate of efflux measured 275 Leishmania strains, isolated from patients and dogs from Greece and Cyprus, was measured and mapped to study the geographical distribution of the multidrug resistance (MDR) gene expression as an indication of the drug resistance of the parasite. The map showed that out of the seven prefectures, where dogs presented high efflux rates, five also had patients with high efflux rates. In one, out of the 59 prefectures studied, the highest number of isolates with efflux slope alpha > 1, in both human and dog isolates, was found; a fact which may suggest that spread of drug resistance is taking place. The virulence of the Leishmania strains, assessed after infecting human macrophages of the THP-1 cell line, fluctuated from 1% to 59.3% with only 2.5% of the isolates showing infectivity > 50%. The most virulent strains were isolated from Attica and Crete. PMID- 27001765 TI - Novel Small-Molecule CX3CR1 Antagonist Impairs Metastatic Seeding and Colonization of Breast Cancer Cells. AB - Recent evidence indicates that cancer cells, even in the absence of a primary tumor, recirculate from established secondary lesions to further seed and colonize skeleton and soft tissues, thus expanding metastatic dissemination and precipitating the clinical progression to terminal disease. Recently, we reported that breast cancer cells utilize the chemokine receptor CX3CR1 to exit the blood circulation and lodge to the skeleton of experimental animals. Now, we show that CX3CR1 is overexpressed in human breast tumors and skeletal metastases. To assess the clinical potential of targeting CX3CR1 in breast cancer, a functional role of CX3CR1 in metastatic seeding and progression was first validated using a neutralizing antibody for this receptor and transcriptional suppression by CRISPR interference (CRISPRi). Successively, we synthesized and characterized JMS-17-2, a potent and selective small-molecule antagonist of CX3CR1, which was used in preclinical animal models of seeding and established metastasis. Importantly, counteracting CX3CR1 activation impairs the lodging of circulating tumor cells to the skeleton and soft-tissue organs and also negatively affects further growth of established metastases. Furthermore, nine genes were identified that were similarly altered by JMS-17-2 and CRISPRi and could sustain CX3CR1 prometastatic activity. In conclusion, these data support the drug development of CX3CR1 antagonists, and promoting their clinical use will provide novel and effective tools to prevent or contain the progression of metastatic disease in breast cancer patients. IMPLICATIONS: This work conclusively validates the instrumental role of CX3CR1 in the seeding of circulating cancer cells and is expected to pave the way for pairing novel inhibitors of this receptor with current standards of care for the treatment of breast cancer patients. Mol Cancer Res; 14(6); 518-27. (c)2016 AACR. PMID- 27001766 TI - End TB strategy: the need to reduce risk inequalities. AB - BACKGROUND: Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases. DISCUSSION: Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle. PMID- 27001767 TI - Infectious canine hepatitis in red foxes (Vulpes vulpes) in wildlife rescue centres in the UK. AB - Outbreaks of infectious canine hepatitis are described in red foxes ( ITALIC! Vulpes vulpes) at two wildlife rescue centres in the UK. Disease occurred in two month-old to four-month-old juvenile foxes, which were held in small enclosures in groups of three to eight animals. The foxes died or were euthanased after a short clinical course, sometimes including neurological signs and jaundice, with a high case fatality rate. Four red foxes submitted for postmortem examination had enlarged, congested livers, with rounded borders and mild accentuation of the lobular pattern. On histological examination, there was random, multifocal to massive hepatic necrosis, along with multifocal vasculitis in the central nervous system (CNS) and mild, multifocal glomerulonephritis. Intranuclear inclusion bodies, typical of canine adenovirus type 1 (CAV-1) infection, were present in hepatocytes, vascular endothelial cells in the CNS, renal glomeruli and renal tubular epithelial cells. CAV-1 was detected in tissues from affected foxes by PCR and sequencing. Congregation of juvenile foxes in wildlife rescue centres is likely to be a risk factor for transmission of CAV-1. Preventive measures in wildlife centres should be implemented to prevent the spread of the virus among conspecifics and to other susceptible species. PMID- 27001768 TI - Player Load in Elite Netball: Match, Training, and Positional Comparisons. AB - CONTEXT: The activity profile of competition and training in elite netball has not been comprehensively reported in the literature. PURPOSE: To measure and analyze player load in elite netballers during matches and training sessions. The primary research question was, How does player load vary between playing positions in a match and between matches and training sessions? METHODS: Various measures of player load were recorded in 12 elite professional netballers with a mean +/- SD age of 26 +/- 4.9 y and height of 183.2 +/- 8.7 cm. Player load was assessed using a published method that uses accelerometry. Load was represented as total load in arbitrary units (au), playing intensity (au/min), and relative time spent in each of 4 playing intensity zones (low, low to moderate, moderate, and high). Data from 15 games and up to 17 training sessions were analyzed for each player. RESULTS: Player load in matches for the goal-based positions (goal shooter, goal keeper, and goal defense) tended to be lower than the attacking and wing-based positions (goal attack, wing attack, wing defense, and center). The difference was largely due to the amount of time spent in low-intensity activity. Playing intensity of matches was greater than in training sessions; however, the total time spent in moderate- to high-intensity activities was not practically different. CONCLUSIONS: Accelerometry is a valuable method of measuring player load in netball, and the present results provide new information about the activity profile of different playing positions. PMID- 27001769 TI - [Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests]. AB - Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course. PMID- 27001770 TI - [Neurophysiology of Vasculitic Peripheral Neuropathy]. AB - Nerve conduction studies (NCSs) are essential to the work up of peripheral neuropathy. NCSs are useful in vasculitic neuropathy because they can serve as a guide in the nerve biopsy, as well as detect asymptomatic vasculitic neuropathy. NCSs characteristically show axonal loss of motor and sensory fibers with asymmetric or non-length-dependent patterns. Occasionally, conduction block (CB) or pseudo CB are observed. Pseudo CB is appears in the acute phase before Wallerian degeneration has developed distal to the infarcted nerve, and then disappears within two weeks. PMID- 27001771 TI - [Pathology of Vasculitic Neuropathies]. AB - Prompt diagnosis of vasculitis is necessary because neuropathy may be the first symptom of vasculitic syndrome, and it is crucial for the management of patients. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, rheumatoid vasculitis, cryoglobulinemia, Sjogren's syndrome, and non-systemic vasculitic neuropathy are disorders frequently associated with vasculitic neuropathy. Pathological features such as the size of the involved vessels and the type of inflammatory cells, combined with general symptoms and laboratory data, may contribute to the specific diagnosis. ANCA may be involved in the pathogenesis of microscopic polyangiitis, and eosinophilic toxins may injure the nerve fibers in some patients with eosinophilic granulomatosis with polyangiitis. We detected B cell follicle-like structures adjacent to the inflamed vessels in rheumatoid vasculitis, which may be associated with the pathogenesis. PMID- 27001772 TI - [Non-systemic Vasculitic Neuropathy]. AB - Non-systemic vasculitic neuropathy (NSVN) is a vasculitis confined to the peripheral nervous system. It is one of the most common causes of vasculitic neuropathy, along with microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). It remains unclear whether this disease is truly an isolated nosological entity, or part of the spectrum of systemic vasculitides. Anti-neutrophil cytoplasmic antibodies (ANCA) are negative in NSVN even though the size of affected vessels in this disease is similar to that in ANCA-associated vasculitis. Although the concept of single organ vasculitis was added to the 2012 revised International Chapel Hill Consensus Conference (CHCC) nomenclature of vasculitides, a description of NSVN has not yet been incorporated. Further studies are needed to elucidate the pathogenesis of NSVN, particularly a search for causative antibodies or participation of complement pathways. These studies may help clarify the position of NSVN along the spectrum of vasculitides based on CHCC nomenclature. PMID- 27001773 TI - [Evidence-based Treatment for Vasculitic Neuropathies]. AB - Vasculitic neuropathies are caused by ischemic damage due to vessel wall inflammation. This damage may cause axonal degeneration leading to permanent neurological disabilities. Therefore, early initiation of effective treatment is crucial. For primary systemic vasculitis, a combined treatment of corticosteroid and immunosuppressive agents is recommended in the evidence-based guidelines as initial standard therapy for induction of remission. However, limited data are available regarding therapies for vasculitic neuropathies and it remains unclear whether combined treatment should be employed as an initial therapy for all patients with vasculitic neuropathies. In approximately half the patients with vasculitic neuropathies, monotherapy with corticosteroids is insufficient in preventing long-lasting neurological disabilities. Addition of intravenous immunoglobulin at an early stage of the disease may be a promising treatment option obviating the need for potent but potentially harmful immunosuppressive agents in some mild or localized cases. PMID- 27001774 TI - [Molecular Genetics as Best Evidence in Glioma Diagnostics]. AB - The development of a genomic landscape of gliomas has led to the internally consistent, molecularly-based classifiers. However, development of a biologically insightful classification to guide therapy is still ongoing. Further, tumors are heterogeneous, and they change and adapt in response to drugs. The challenge of developing molecular classifiers that provide meaningful ways to stratify patients for therapy remains a major challenge for the field. Therefore, by incorporating molecular markers into the new World Health Organization (WHO) classification of tumors of the central nervous system, the traditional principle of diagnosis based on histologic criteria will be replaced by a multilayered approach combining histologic features and molecular information in an "integrated diagnosis", to define tumor entities as narrowly as possible. We herein review the current status of diagnostic molecular markers for gliomas, focusing on IDH mutation, ATRX mutation, 1p/19q co-deletion, and TERT promoter mutation in adult tumors, as well as BRAF and H3F3A aberrations in pediatric gliomas, the combination of which will be a promising endeavor to render molecular genetics as a best evidence in the glioma diagnositics. PMID- 27001775 TI - [Neuroanatomy of Isolated Body Lateropulsion]. AB - Axial body lateropulsion, a phenomenon where the body is pulled toward the side of the lesion, with tendency of falling down, is the well-known transient feature of lateral medullary syndrome. In some cases, axial body lateropulsion occurs without vestibular and cerebellar symptoms (isolated body lateropulsion:[iBL]). Patients with iBL have a lesion located in the spinocerebellar tract, descending lateral vestibulospinal tract, vestibulo-thalamic pathway, dentatorubrothalamic pathway, or thalamocortical fascicle. This review deals with the anatomic basis and clinical significance of iBL. PMID- 27001776 TI - [Cerebellar Control of Ocular Movements: Application to the Topographical Diagnosis of Cerebellar Lesions]. AB - Over the last decade, substantial information on cerebellar oculomotor control has been provided by the use of sophisticated neuroanatomical, neurophysiological, and imaging techniques. We now know that an intact cerebellum is a prerequisite for normal oculomotor performance. This review clarifies the current knowledge on structure-function correlations of the cerebellum in relation to ocular movements and allows them to be applied to topographical diagnosis of cerebellar lesions. The cerebellar regions most closely related to oculomotor function are: (1) the flocculus/paraflocculus for VOR suppression, cancellation, smooth pursuit eye movement and gaze-holding, (2) the nodulus/ventral uvula for velocity storage and low frequency prolonged vestibular response, and (3) the dorsal oculomotor vermis (declive VI, folium VII) and the posterior portion of the fastigial nucleus (fastigial oculomotor region) for saccades and smooth pursuit initiation. Symptomatically, defects in the flocculus/parflocculus cause saccadic pursuit, downbeat nystagmus, and impairments to visual suppression of the VOR. Lesions of the nodulus/uvula reveal as periodic alternating nystagmus. Lesions of the oculomotor vermis and the fastigial nucleus can induce saccadic dysmetria, while fastigial nucleus lesions may also cause ocular flutter/opsoclonus. A detailed knowledge of cerebellar anatomy and the physiology of eye movements enables localization of lesions to specific areas of the cerebellum. PMID- 27001777 TI - [A Patient with Acute Limbic Encephalitis Associated with Anti-Glutamate Receptor Antibodies and Subsequent Optic Neuritis]. AB - A 19-year-old woman presented with headache and fever. Cerebrospinal fluid (CSF) analysis revealed increased pressure (>200 mmH2O) and pleocytosis. Brain MRI showed high intensity in the medial part of the right temporal lobe, insular regions, and basal ganglia of the right hemisphere on fluid attenuated inversion recovery images. Based on a tentative diagnosis of limbic encephalitis caused by viral infection, acyclovir therapy was started. However, 10 days after admission, a right superior temporal quadrantanopia developed in the left eye. MRI detected abnormal intensity in the left optic nerve on short tau inversion recovery images. After three courses of steroid pulse therapy, the optic neuritis quickly improved and the patient was maintained on subsequent oral administration of prednisolone, without relapse for one year. The CSF was positive for anti glutamate receptor (GluR) antibodies (GluN2B, GluN1, and GluD2); however, anti-N methyl-D-aspartate receptor antibody was not detected in both serum and CSF with cell-based asseys. Compared to previously reported anti-GluR positive cases combined with optic neuritis, the clinical outcome of our patient was short, with good prognosis. Our results indicate that an autoimmune mechanism involving anti GluR antibodies contributes to the pathogenesis of optic neuritis as well as limbic encephalitis. PMID- 27001778 TI - [BIOLOGICAL IMPLANTS IN ABDOMINAL WALL HERNIA REPAIR (REVIEW)]. AB - The use of synthetic meshes as a material for abdominal wall hernia repair does not always ensure a recurrence-free treatment outcome and full recovery of the abdominal wall functional activity. There are well-known disadvantages such as poor resistance to infection, the infiltrate formation in the place of implantation, expressed adhesive process in cases of introperitoneal fixation, to create certain restrictions on the using of these implants for abdominal wall reconstruction. The search for alternative materials that could minimize the risk of complications, has led to the study of biological grafts. It is known that various methods for the manufacturing biological implants determine endogenous properties for each material separately, and may be cause a variety of biological responses in vivo after implantation. The question has not been resolved, what the fresh raw material is better to use for derive biological implants. In this review we investigated the interaction of different types of biological implants between the abdominal wall and the organs of abdominal cavity of the recipient, their ability to resist infection and the development of relapses, as a leading indicator of the effectiveness of hernioplasty. PMID- 27001779 TI - [THE CHARACTER OF EXPRESSION AND THE ROLE OF APOPTOSIS MARKERS IN THE DEVELOPMENT OF PLACENTAL DYSFUNCTION IN PREGNANT WITH UROGENITAL INFECTIONS]. AB - The aim of the current study was to examine the expression level and possibilities of apoptotic markers in realization of placental insufficiency in pregnant women with urogenital infections. The study was conducted on 250 pregnant women with urogenital infections (1-st group - 50 pregnant women with bacterial infections (Chlamydia, ureaplasma, mycoplasma), 2-nd group - 50 pregnant women with viral infections (CMV and herpes simplex virus), 3-rd group - 150 patients with mixed viral and bacterial infections) and 50 pregnant women with normal pregnancy. The content of apoptosis inducers: sFasL and TNF-alpha in blood serum of pregnant women was determined; the level of caspase-3 in placental sample was analyzed; sonographic examination of the placenta was performed. Maximal indices of apoptosis inducers were observed in the 3-rd group (with mixed viral and bacterial infections). Changes in the placenta according to ultrasound data were determined in all pregnant women with urogenital infections. It was suggested that increased placental cell death in apoptosis might be one of the key points, triggering the development of placental dysfunction. PMID- 27001781 TI - [ORIGINAL PERFORMANCE OF THE INTEGRATED CIRCUITS NEUROPROTECTIVE LECHNIYA ANTERIOR ISCHEMIC OPTIC NEUROPATHY DEPENDING ON BLOOD PRESSURE]. AB - Anterior ischemic optic neuropathy (AION) is one of the main reasons of vision disorders among middle-aged and elderly people. During the examination of patients with AION, we were interested by the fact of low efficiency of the standard treatment course. Moreover, over 60% of such patients underwent the development of AION on the other eye during 1 year after the beginning of the disease. The purpose of the given study is the development of efficient and original neuroprotection treatment scheme for AION, depending on the arterial pressure rate. We examined 58 patients (65 eyes) with AION, depending on the arterial pressure rate. The patients were divided into two clinical groups. For the first group of 38 patients (38 eyes), we used the original AION treatment scheme developed by us. The group was divided into 3 subgroups, depending on their arterial pressure rate: patients with normal ap., patients with hypertension of I-II stages and patients with hypotension. For the control group, the standard treatment scheme was used. The results received allow us to make a conclusion that the original treatment scheme, developed by us, is more efficient, and it can be recommended as a neuroprotection treatment scheme for AION among the patients with arterial hypertension of I-II stages. PMID- 27001780 TI - INTRA-ARTERIAL INFUSIONS AND DOPLEROGRAPIC CONTROL FOR COMPLEX TREATMENT OF UPPER AND MIDDLE FACIAL ZONES, CONCOMITANT WITH TRAUMATIC CRANIOCEREBRAL INJURIES. AB - Maxillofacial traumatic injuries concomitant with craniocerebral trauma are still considered as an actual problem in emergency medicine. For this category of patients one of the dangerous and severe complications is development of inflammatory process in the injured areas. Fracture lines of upper and middle facial zones pass through the accessory sinuses of the nose, maxillary/upper dental arch area and are considered to be open and infected fractures. Combination of these fractures with craniocerebral injuries and especially, with open traumas creates predisposition for development of inflammatory processes in CNS that can result in heavy outcome. 29 patients (among them 5-females and 24 males) with severe and open craniofacial fractures were observed by the authors. For prevention of inflammatory complications in complex treatment of the patients, intra-arterial infusions of therapeutic agents (wide spectrum of antibiotics, Heparin) were used for stimulation of reparative regeneration in fractured fragments of facial bones. After the main surgical interventions (neurosurgery, surgery of facial bones) sanitation of infected centers (accessory sinuses of the nose, oral cavity) and catheterization of external carotid arteries through the temporal arteries were performed. According to the severity of the trauma and its preferential localization, catheterization of carotid arteries was conducted unilaterally (12 cases) or bilaterally (17 cases). Insertion depth through femoral artery was 6-8 cm. Catheter was stayed in the artery for 7-8 days. Intra-arterial infusions were carried out in the morning and evening. Therapeutic agents for arterial infusion included: antibiotic (Rocephin and its analogues), Heparin. To determine the effectiveness of vascular therapy dopplerography of external carotid artery, its branches and supratrochlear artery was performed. Dopplerography of supratrochlear artery, which is the branch of internal carotid artery, was conducted to detect the impact of therapeutic agents, administered in external carotid artery, on the internal carotid artery. During the treatment of complicated concomitant craniofacial injuries in a sequential order, development of inflammatory processes was not observed even in the patients with basic inflammatory processes in accessory sinuses of the nose. After infusion of therapeutic agents to external carotid artery, dopplerographically, sharp increase in blood flow in main artery and its branches, indicates to the stimulation of microcirculation that serves as a guarantee for osteogenic type healing of fractured fragments. PMID- 27001782 TI - THE EFFECTIVENESS OF PHYSICAL FACTORS IN THE TREATMENT OF COMPRESSION-DISLOCATION DYSFUNCTION OF THE TEMPOROMANDIBULAR JOINT. AB - The aim of the study was clinical and functional assessment of the effectiveness of physical factors in the treatment of patients with compression-dislocation dysfunction of the temporomandibular joint. We observed two groups of patients. All patients were undergone the repositioning of the joint heads of the lower jaw. Patients of the index group were assigned a vibrating massage of all masseter muscles, tourmaline ceramic on the joint area and a local physical therapy. Patients in the control group had only lidocaine blockade of periarticular area twice a week. Treatment efficacy was evaluated on the eighth day after the start of the treatment according to the bioelectric activity of the genuine masseter and temporal muscles, the intensity of pain according to in Visual Analog Scale, and according to the results of the clinical examination. In most patients of the index group the electromyography data after treatment were approaching to norm, the phenomenon of dysfunction of the temporomandibular joints was reversed. In the control group the full restoration of the functional activity of muscle did not occur. The addition to the complex of therapeutic measures a vibration massage, tourmaline ceramics and local physical therapy for patients with dysfunction of the temporomandibular joints allows to get a positive effect. PMID- 27001783 TI - CLINICAL AND PHARMACEUTICAL ASPECTS OF THE USE OF ANTITHROMBOTIC DRUGS IN PATIENTS SUFFERING FROM ISCHEMIC HEART DISEASE (REVIEW). AB - The review article discusses the possibilities and evidence base of the use of antithrombotic drugs in common clinical practice. Presents information about the basic clinical trials of the effectiveness of antithrombotic medications (CAPRIE, CURE, VA, RISC, ISIS2, PLATO) in the treatment and secondary prevention of the consequences of atherothrombosis. Also presents the algorithms for prescription of antithrombotic drugs and the principles of rational use of antiplatelet agents. PMID- 27001784 TI - OPTIMUM APPLICATION OF MODERN ANTITHROMBOTIC DRUGS AMONG PATIENTS WITH THE ACUTE CORONARY SYNDROME WITH THE RISK OF STRICTURE FORMATION OF CORONARY ARTERIES. AB - The purpose of the research is to give the effectiveness and safety of ticagrelor in combination with acetylsalicylic acid as preoperative treatment of primary stenting in patients with ACS. We have investigated 42 patients with ACS, 3 of which were diagnosed with cardiogenic shock, age from 38 to 82 years (63 +/- 6.5 years). The ACS diagnosis was verified using the results of the ECG, a troponin test and x-ray contrast coronary angiography. The purpose of preoperative antiplatelet treatment prior to primary PCI ticagrelor was administered in the dose of 180 mg and aspirin at a dose of 200 mg. Emergency coronary angiography and primary PCI was performed 15-90 minutes from the time of diagnosis. TIMI III flow in the infarct-related coronary arteries was achieved in all patients. None of the patients the phenomenon of "No-Reflow" has not developed. The appointment of the antiplatelet drug ticagrelor before primary PCI contributes to the achievement of full blood flow restoration in the infarct-related coronary artery, and also reduces the risk of intraoperative and postoperative complications. PMID- 27001785 TI - GENDER AND PROFESSIONAL FACTORS OF MEDICAL STUDENTS' PSYCHOLOGICAL READINESS FOR PERFORMING PROFESSIONAL DUTIES. AB - The article describes the results of the psychological readiness for performing professional duties study performed in 2010-2015 among the O.Bogomolets' National medical university students; contains analysis of the gender and professional factors of the readiness. The authors have described the results obtained in motivation, cognitive, conative, emotional and communicative components of the psychological readiness by using the classic and author authentic methods. It has been estimated that the female respondents are characterized by a higher level of psychological readiness than the male ones, which may be explained due to higher female conformity resulting from higher demands for profession. The conducted analysis of professional factors of the psychological readiness has shown that the students of the "Preventive medicine" specialization exhibit higher level of psychological readiness than the "Pediatrics" and "Stomatology" specialization students due to dominating altruistic motivation of professional activity, independent career choice and higher level of the emotional component development. PMID- 27001786 TI - [FEATURES BONE METABOLISM IN ADOLESCENTS LIVING IN KAZAKHSTAN (ON THE EXAMPLE AKTOBE)]. AB - The purpose of this work is to study by densitometry the bone mineral density (BMD) in Kazakhstan adolescents of Aktobe and biological markers of the bone metabolism. By obtained data revealed the presence of osteopenia among apparently healthy Kazakhstan adolescents in 72% of cases. Indicators of bone mineral density in adolescents two ethnic groups (Kazakhs and Russian) were unremarkable. Sexual features of the BMD concluded that the sign of osteoporosis was 1.5 times higher among boys than girls. Remodeling of bone tissue in the examined pupils was due to the markers of osteosynthesis and osteoresorption respectively PINP and beta-CrossLaps with their strong correlation (r=0.8) in normal and reduced BMD. Reduced BMD in Kazakhstan adolescents is reflected in increased value of the marker beta-CrossLaps and humoral regulator of PTH, responsible for osteoresorbtion of the overall process of the bone remodeling. PMID- 27001787 TI - NEVUS FLAMMEUS ASSOCIATED WITH DYSPLASTIC NEVI AND LICHEN SCLEROSUS: THE FIRST REPORT IN THE MEDICAL LITERATURE. AB - We describe a rare case of a 28 year-old male patient presenting with pruritus and increased sensitivity of the prepuce accompanied by erythematous confluent papules, unilateral nevus flammeus (NF) along almost the whole length of the right lower limb and two dysplastic nevi (DN), one located on the mid back and the other on the medial border of the right fifth toe, the latter coinciding with the NF. A biopsy of the prepuce revealed lichen sclerosus et atrophicus (LSA). Mental health assessment revealed anxiety disorder and predisposition to panic attacks. Several clinical, paraclinical and histopathological examinations were undertaken to evaluate potential underlying factors for such unusual combination of findings. Both dysplastic nevi were surgically removed. A topical calcineurin inhibitor treatment of the LSA was prescribed. For the first time in medical literature, we report an extremely rare association of NF, DN (including DN over NF) and LSA, and we are focusing our discussion on a potentially common genetic background which could explain this unusual combination of different diseases, which could in turn be caused by different mutations in common genes and/or different genes with close location in the genome. PMID- 27001788 TI - [A STUDY OF IMPACT OF MERCURY CHLORIDE ON MYOCARDIUM IN EXPERIMENT]. AB - The article is devoted to the study of the myocardium structural reorganization features under the action of 0,01 LD50 of mercury chloride (II) rats when comparing chronic (30 injections) and subchronic (10 injections) exposures. Structural-metabolic reorganization of the myocardium was studied using histological, histochemical and electron microscopic methods. Computer morphometric analysis with subsequent statistical processing was applied. It was established that the main mechanisms of cardiotoxic effect of mercuric chloride are: hypoxia (due to damage to micro vessels; disorder of myogenic regulation at the expense of damage intercalated discs) and the appearance of cell detrits and abnormal proteins as a result of the destruction of cardiomyocytes. Sensitive to the toxic effects of chloride mercuric in low doses are myofibrils, sarcoplasmic network and the energy apparatus of cardiomyocytes - the mitochondria. It was found that chronic exposure to low doses of mercuric chloride causes non-specific qualitative and quantitative changes in all structural components of the heart, damage to the tissue barrier is ongoing and dynamic and resorptive insufficiency hemomicrocirculatory bed of the heart that leads to chronic swelling that causes the development of diffuse fibrosis and enhances cardiac decompensation activities. PMID- 27001789 TI - ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY). AB - Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability. PMID- 27001790 TI - [REACTIVE CHANGES IN SPINAL CORD MOTONEURONS AFTER SCIATIC NERVE INJURY AFTER HIGH-FREQUENCY ELECTROSURGICAL INSTRUMENT APPLICATION]. AB - A new experimental model for tissues connection at peripheral nerve injury site in form of tissues welding was designed. In current study we investigated motoneuron state 1, 3, 6 and 12 weeks after peripheral nerve injury and surgical repair with high-frequency electrosurgical technology. Spinal cord sections was stained by Nissl method and observed with light microscopy. We found that postoperative period in animals from experimental groups characterized by qualitative changes in neurons from spinal motor centers that can be interpreted as compensatory processes as response to alteration. In animals from group with high-frequency electrosurgical technology usage stabilization processes passes more quickly comparatively to animals with epineural sutures. High-frequency electrosurgical technology usage provides less harmful effects on motoneurons than epineural suturing. PMID- 27001791 TI - CHANGES OF LIPOPEROXIDATION AND ANTIOXIDATIVE ENZYMES DURING CRUSH-SYNDROME MODELLING. AB - Crush-syndrome (CS) is characterized by numerous pathological deviations due to the soft tissue damage and their further reperfusion. The aim of the study was to investigate pro- and antioxidative processes during different regimens of crush syndrome. The experiment was carried out on randomly selected 200-250gr. mass 50 laboratory rats using crush syndrome modeling classical method. Investigations were conducted at various stages of compression and decompression period. Activity of antioxidant enzymes - total ceruloplasmin, oxidized ceruloplasmin was determined in blood serum. LOO. and free oxygen species were as well determined with the use of relevant methods. According to our findings we can conclude that: - Lipoperoxidation intensity increases in compliance with crush syndrome duration; - Short-term (3-hour) compression causes enhancement of lipoperoxidation however, in further 1 hour decompression there is revealed a trend toward normalization of processes. Lipoperoxides and free oxygen species content decreases and the antioxidant enzymes activity is almost restored; - Long lasting compression (6 hours) leads to severe disorders in the body (total ceruloplasmin impaired production and after 6 hours from decompression antioxidant enzymes inactivation). PMID- 27001792 TI - The living legacy of a biomaterials founder: remembering Samuel F Hulbert, PhD. PMID- 27001793 TI - Sensitivity and accuracy of Sensitherm/Esotherm oesophageal temperature probe. PMID- 27001794 TI - Sensitivity and accuracy of Sensitherm/Esotherm oesophageal temperature probe: reply. PMID- 27001795 TI - Health-care-related adverse events leading to admission in older individuals: incidence, predictive factors and consequences. AB - BACKGROUND: Older individuals are particularly prone to suffer health-care related adverse events (AEs); they often have more comorbidity and, thus, require more health-care. Since our society is ageing, insight into AEs leading to hospital admissions is necessary. We aimed to assess the incidence, predictive factors and consequences of AEs leading to admission in older individuals. METHODS: We performed a retrospective cohort study of all older patients (>=65 years) who were admitted through the emergency department (ED) to the department of internal medicine in the last week of every month in 2011. We retrieved the incidence and possible predictive factors for AEs leading to admission and mortality (both in-hospital and within 28 days after discharge). The control group consisted of older patients admitted because of other reasons. RESULTS: In the study period, there were 262 admissions, of which 106 (40.5%) were because of an AE. The most common AE was medication-related (55.7%). Predictive factors of admission because of an AE were the number of medications used [odds ratio (OR) 1.16 per medication, 95% confidence intervals (CI) 1.08-1.25] and dependency in instrumental activities of daily living (IADL) (OR 0.35, 95% CI 0.14-0.91). Both in-hospital mortality and mortality within 28 days after discharge were lower in the AE group (5.7% vs. 16.0%, P = 0.01, and 0 vs. 6.9%, P < 0.05, respectively). CONCLUSION: Admissions through the ED to the department of internal medicine of older patients are often because of AEs (40.5%), with medication use being the greatest culprit. Surprisingly, mortality was lower in the AE group. The number of medications used (positive) and IADL dependency (negative) were predictive factors for being admitted because of an AE. PMID- 27001796 TI - Incidence and Prevalence of Opportunistic and Other Infections and the Impact of Antiretroviral Therapy Among HIV-infected Children in Low- and Middle-income Countries: A Systematic Review and Meta-analysis. AB - BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the incidence and prevalence of 14 opportunistic infections (OIs) and other infections as well as the impact of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected children (aged <18 years) in low- and middle-income countries (LMICs), to understand regional burden of disease, and inform delivery of HIV services. METHODS: Eligible studies described the incidence of OIs and other infections in ART-naive and -exposed children from January 1990 to November 2013, using Medline, Global Health, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Knowledge, and Literatura Latino Americana em Ciencias da Saude databases. Summary incident risk (IR) and prevalent risk for each OI in ART-naive and ART-exposed children were calculated, and unadjusted odds ratios calculated for impact of ART. The number of OI cases and associated costs averted were estimated using the AIDS impact model. RESULTS: We identified 4542 citations, and 88 studies were included, comprising 55 679 HIV infected children. Bacterial pneumonia and tuberculosis were the most common incident and prevalent infections in both ART-naive and ART-exposed children. There was a significant reduction in IR with ART for the majority of OIs. There was a smaller impact on bacterial sepsis and pneumonia, and an increase observed for varicella zoster. ART initiation based on 2010 World Health Organization guidelines criteria for ART initiation in children was estimated to potentially avert >161 000 OIs (2013 UNAIDS data) with estimated cost savings of at least US$17 million per year. CONCLUSIONS: There is a decrease in the risk of most OIs with ART use in HIV-infected children in LMICs, and estimated large potential cost savings in OIs averted with ART use, although there are greater uncertainties in pediatric data compared with that of adults. PMID- 27001797 TI - Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone. AB - BACKGROUND: Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone. METHODS: A survivor clinic opened within an Ebola treatment center compound in Freetown, Sierra Leone. At each visit, clinical and psychological assessments were conducted and free treatment was offered. Survivors were referred to a partner's hospitals if their condition could not be managed in the clinic. We used routinely collected data from the clinic to describe long-term complications of EVD and their risk factors. RESULTS: A total of 1001 medical consultations for 166 patients were performed between 3 February and 21 June 2015. The most frequent complaints and diagnoses were arthralgia (n = 129 [77.7%]), fatigue (n = 116 [69.8%]), abdominal pain (n = 90 [54.2%]), headache (n = 87 [52.4%]), anemia (n = 83 [50%]), skin disorders (n = 81 [48.8%]), back pain (n = 54 [32.5%]), and alopecia (n = 53 [31.9%]). Ocular complications were diagnosed in 94 survivors (56.7%); uveitis was the most common (n = 57 [34%]). Survivors were 10 times more likely to develop uveitis post-EVD if they presented with red/injected eyes during the acute phase of their illness. CONCLUSIONS: Post EVD complications among our patients were similar to those described previously and were detected early following the acute phase of disease. Follow-up of survivors should begin immediately after discharge to address sequelae as they arise and reduce the potential for development of long-term disabilities such as blindness. PMID- 27001798 TI - Cytomegalovirus Immunity and Exhaustive CD8+ T Cell Proliferation in Treated Human Immunodeficiency Virus Infection. PMID- 27001800 TI - Effects of CD4 Cell Counts and Viral Load Testing on Mortality Rates in Patients With HIV Infection Receiving Antiretroviral Treatment: An Observational Cohort Study in Rural Southwest China. AB - BACKGROUND: Recent studies have suggested that CD4 cell count monitoring has little added value in patients who are virologically suppressed and immunologically stable if viral load (VL) testing is routinely available. These conclusions have not been directly assessed using mortality rate as a study end point in a real-world setting. METHODS: This human immunodeficiency virus (HIV) treatment cohort study from 2008 to 2014 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between the frequency of CD4 cell counts and VL testing and death. RESULTS: Compared with monitoring CD4 cell counts >=3 times during the first year of antiretroviral therapy (ART) initiation, as currently suggested by the Chinese National Free Antiretroviral Treatment Program, monitoring them less than twice during the first year of ART was significantly associated with death; however, monitoring them twice in that year did not significantly increase mortality rates. Compared with testing VL at least once during the first year of ART, as currently suggested by the National Free Antiretroviral Treatment Program, performing no VL tests in the first year after ART initiation was significantly associated with higher mortality rates. Routine CD4 cell count monitoring did not have an impact on mortality rates among HIV-infected patients with VLs <1000 copies/mL or CD4 cell counts >=350/MUL beyond 12 months after ART initiation. CONCLUSIONS: Our study suggests that CD4 cell counts can be reduced to twice during the first year of ART and be reduced or stopped for patients who have achieved virologic suppression or immunologic stability after 12 months of treatment. PMID- 27001799 TI - Multistate Outbreak of Respiratory Infections Among Unaccompanied Children, June 2014-July 2014. AB - BACKGROUND: From January 2014-July 2014, more than 46 000 unaccompanied children (UC) from Central America crossed the US-Mexico border. In June-July, UC aged 9 17 years in 4 shelters and 1 processing center in 4 states were hospitalized with acute respiratory illness. We conducted a multistate investigation to interrupt disease transmission. METHODS: Medical charts were abstracted for hospitalized UC. Nonhospitalized UC with influenza-like illness were interviewed, and nasopharyngeal and oropharyngeal swabs were collected to detect respiratory pathogens. Nasopharyngeal swabs were used to assess pneumococcal colonization in symptomatic and asymptomatic UC. Pneumococcal blood isolates from hospitalized UC and nasopharyngeal isolates were characterized by serotyping and whole-genome sequencing. RESULTS: Among 15 hospitalized UC, 4 (44%) of 9 tested positive for influenza viruses, and 6 (43%) of 14 with blood cultures grew pneumococcus, all serotype 5. Among 48 nonhospitalized children with influenza-like illness, 1 or more respiratory pathogens were identified in 46 (96%). Among 774 nonhospitalized UC, 185 (24%) yielded pneumococcus, and 70 (38%) were serotype 5. UC transferring through the processing center were more likely to be colonized with serotype 5 (odds ratio, 3.8; 95% confidence interval, 2.1-6.9). Analysis of core pneumococcal genomes detected 2 related, yet independent, clusters. No pneumococcus cases were reported after pneumococcal and influenza immunization campaigns. CONCLUSIONS: This respiratory disease outbreak was due to multiple pathogens, including Streptococcus pneumoniae serotype 5 and influenza viruses. Pneumococcal and influenza vaccinations prevented further transmission. Future efforts to prevent similar outbreaks will benefit from use of both vaccines. PMID- 27001802 TI - Editorial Commentary: Resurrecting a Live Oral Cholera Vaccine. PMID- 27001801 TI - Does Increasing Treatment Frequency Address Suboptimal Responses to Ivermectin for the Control and Elimination of River Blindness? AB - BACKGROUND: Several African countries have adopted a biannual ivermectin distribution strategy in some foci to control and eliminate onchocerciasis. In 2010, the Ghana Health Service started biannual distribution to combat transmission hotspots and suboptimal responses to treatment. We assessed the epidemiological impact of the first 3 years of this strategy and quantified responses to ivermectin over 2 consecutive rounds of treatment in 10 sentinel communities. METHODS: We evaluated Onchocerca volvulus community microfilarial intensity and prevalence in persons aged >=20 years before the first, second, and fifth (or sixth) biannual treatment rounds using skin snip data from 956 participants. We used longitudinal regression modeling to estimate rates of microfilarial repopulation of the skin in a cohort of 217 participants who were followed up over the first 2 rounds of biannual treatment. RESULTS: Biannual treatment has had a positive impact, with substantial reductions in infection intensity after 4 or 5 rounds in most communities. We identified 3 communities all having been previously recognized as responding suboptimally to ivermectin with statistically significantly high microfilarial repopulation rates. We did not find any clear association between microfilarial repopulation rate and the number of years of prior intervention, coverage, or the community level of infection. CONCLUSIONS: The strategy of biannual ivermectin treatment in Ghana has reduced O. volvulus microfilarial intensity and prevalence, but suboptimal responses to treatment remain evident in a number of previously and consistently implicated communities. Whether increasing the frequency of treatment will be sufficient to meet the World Health Organization's 2020 elimination goals remains uncertain. PMID- 27001803 TI - Reply to Barrett, et al. PMID- 27001805 TI - Transcatheter Replacement of Stenotic Aortic Valve Normalizes Cardiac-Coronary Interaction by Restoration of Systolic Coronary Flow Dynamics as Assessed by Wave Intensity Analysis. AB - BACKGROUND: Aortic valve stenosis (AS) can cause angina despite unobstructed coronary arteries, which may be related to increased compression of the intramural microcirculation, especially at the subendocardium. We assessed coronary wave intensity and phasic flow velocity patterns to unravel changes in cardiac-coronary interaction because of transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Intracoronary pressure and flow velocity were measured at rest and maximal hyperemia in undiseased vessels in 15 patients with AS before and after TAVI and in 12 control patients. Coronary flow reserve, systolic and diastolic velocity time integrals, and the energies of forward (aorta-originating) and backward (microcirculatory-originating) coronary waves were determined. Coronary flow reserve was 2.8+/-0.2 (mean+/-SEM) in control and 1.8+/-0.1 in AS (P<0.005) and was not restored by TAVI. Compared with control, the resting backward expansion wave was 45% higher in AS. The peak of the systolic forward compression wave was delayed in AS, consistent with a delayed peak aortic pressure, which was partially restored after TAVI. The energy of forward waves doubled after TAVI, whereas the backward expansion wave increased by >30%. The increase in forward compression wave with TAVI was related to an increase in systolic velocity time integral. AS or TAVI did not alter diastolic velocity time integral. CONCLUSIONS: Reduced coronary forward wave energy and systolic velocity time integral imply a compromised systolic flow velocity with AS that is restored after TAVI, suggesting an acute relief of excess compression in systole that likely benefits subendocardial perfusion. Vasodilation is observed to be a major determinant of backward waves. PMID- 27001804 TI - Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. AB - BACKGROUND: No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2 dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model. METHODS: Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 * 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 * 10(5) CFU of wild type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. RESULTS: The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (>=3.0 L) to severe (>=5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001). CONCLUSIONS: The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine. CLINICAL TRIALS REGISTRATION: NCT01895855. PMID- 27001806 TI - Assessing Predictive Performance of Published Population Pharmacokinetic Models of Intravenous Tobramycin in Pediatric Patients. AB - Several population pharmacokinetic models describe the dose-exposure relationship of tobramycin in pediatric patients. Before the implementation of these models in clinical practice for dosage adjustment, their predictive performance should be externally evaluated. This study tested the predictive performance of all published population pharmacokinetic models of tobramycin developed for pediatric patients with an independent patient cohort. A literature search was conducted to identify suitable models for testing. Demographic and pharmacokinetic data were collected retrospectively from the medical records of pediatric patients who had received intravenous tobramycin. Tobramycin exposure was predicted from each model. Predictive performance was assessed by visual comparison of predictions to observations, by calculation of bias and imprecision, and through the use of simulation-based diagnostics. Eight population pharmacokinetic models were identified. A total of 269 concentration-time points from 41 pediatric patients with cystic fibrosis were collected for external evaluation. Three models consistently performed best in all evaluations and had mean errors ranging from 0.4 to 1.8 mg/liter, relative mean errors ranging from 4.9 to 29.4%, and root mean square errors ranging from 47.8 to 66.9%. Simulation-based diagnostics supported these findings. Models that allowed a two-compartment disposition generally had better predictive performance than those that used a one compartment disposition model. Several published models of the pharmacokinetics of tobramycin showed reasonable low levels of bias, although all models seemed to have some problems with imprecision. This suggests that knowledge of typical pharmacokinetic behavior and patient covariate values alone without feedback concentration measurements from individual patients is not sufficient to make precise predictions. PMID- 27001807 TI - Investigating the Extremes of Antibiotic Use with an Epidemiologic Framework. AB - Benchmarks for judicious use of antimicrobials are needed. Metrics such as defined daily doses (DDDs) and days of therapy (DOTs) quantify antimicrobial consumption. However, benchmarking with these metrics is complicated by interhospital variability. Thus, it is important for each hospital to monitor its own temporal consumption trends. Time series analyses allow trends to be detected; however, many of these methods are complex. We present simple regressive methods and caveats in using them to define potential antibiotic over- and underutilizations. PMID- 27001808 TI - Emergence and Diversity of Salmonella enterica Serovar Indiana Isolates with Concurrent Resistance to Ciprofloxacin and Cefotaxime from Patients and Food Producing Animals in China. AB - Salmonellosis is a major global foodborne infection, and strains that are resistant to a great variety of antibiotics have become a major public health concern. The aim of this study was to identify genes conferring resistance to fluoroquinolones and extended-spectrum beta-lactams in nontyphoidal Salmonella (NTS) from patients and food-producing animals in China. In total, 133 and 21 NTS isolates from animals and humans, respectively, exhibiting concurrent resistance to ciprofloxacin and cefotaxime were cultured independently from 2009 to ~2013. All of the isolates were identified, serotyped, and subjected to antimicrobial susceptibility testing. Importantly, the isolates with concurrent resistance to ciprofloxacin and cefotaxime all were confirmed as S. enterica serovar Indiana. The presence of fluoroquinolone resistance genes and extended-spectrum beta lactamases (ESBLs) was established by PCR and DNA sequencing. The occurrence and diversity of different genes conferring fluoroquinolone resistance [qepA, oqxAB, and aac(6')-Ib-cr] with mutations in topoisomerase-encoding genes (gyrA and parC) and several ESBLs (including CTX-M-65, CTX-M-27, CTX-M-15, CTX-M-14, and CTX-M 14/CTX-M-15) were noteworthy. Genes located on mobile genetic elements were identified by conjugation and transformation. Pulsed-field gel electrophoresis, used to determine the genetic relationships between these isolates, generated 91 pulsotypes from 133 chicken isolates and 17 pulsotypes from the 21 clinical isolates that showed considerable diversity. Analysis of the pulsotypes obtained with the isolates showed some clones appeared to have existed for several years and had been disseminating between humans and food-producing animals. This study highlights the emergence of ciprofloxacin- and cefotaxime-resistant S. enterica serovar Indiana, posing a threat to public health. PMID- 27001809 TI - SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin Resistant Staphylococcus aureus Strain N315. AB - Increasing cases of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains in healthy individuals have raised concerns worldwide. MRSA strains are resistant to almost the entire family of beta-lactam antibiotics due to the acquisition of an extra penicillin-binding protein, PBP2a. Studies have shown that spoVG is involved in oxacillin resistance, while the regulatory mechanism remains elusive. In this study, we have found that SpoVG plays a positive role in oxacillin resistance through promoting cell wall synthesis and inhibiting cell wall degradation in MRSA strain N315. Deletion of spoVG in strain N315 led to a significant decrease in oxacillin resistance and a dramatic increase in Triton X-100-induced autolytic activity simultaneously. Real-time quantitative reverse transcription-PCR revealed that the expression of 8 genes related to cell wall metabolism or oxacillin resistance was altered in the spoVG mutant. Electrophoretic mobility shift assay indicated that SpoVG can directly bind to the putative promoter regions of lytN (murein hydrolase), femA, and lytSR (the two-component system). These findings suggest a molecular mechanism in which SpoVG modulates oxacillin resistance by regulating cell wall metabolism in MRSA. PMID- 27001810 TI - Secreted Compounds of the Probiotic Bacillus clausii Strain O/C Inhibit the Cytotoxic Effects Induced by Clostridium difficile and Bacillus cereus Toxins. AB - Although the use of probiotics based on Bacillus strains to fight off intestinal pathogens and antibiotic-associated diarrhea is widespread, the mechanisms involved in producing their beneficial effects remain unclear. Here, we studied the ability of compounds secreted by the probiotic Bacillus clausii strain O/C to counteract the cytotoxic effects induced by toxins of two pathogens, Clostridium difficile and Bacillus cereus, by evaluating eukaryotic cell viability and expression of selected genes. Coincubation of C. difficile and B. cereus toxic culture supernatants with the B. clausii supernatant completely prevented the damage induced by toxins in Vero and Caco-2 cells. The hemolytic effect of B. cereus was also avoided by the probiotic supernatant. Moreover, in these cells, the expression of rhoB, encoding a Rho GTPase target for C. difficile toxins, was normalized when C. difficile supernatant was pretreated using the B. clausii supernatant. All of the beneficial effects observed with the probiotic were abolished by the serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF). Suspecting the involvement of a secreted protease in this protective effect, a protease was purified from the B. clausii supernatant and identified as a serine protease (M-protease; GenBank accession number Q99405). Experiments on Vero cells demonstrated the antitoxic activity of the purified protease against pathogen supernatants. This is the first report showing the capacity of a protease secreted by probiotic bacteria to inhibit the cytotoxic effects of toxinogenic C. difficile and B. cereus strains. This extracellular compound could be responsible, at least in part, for the protective effects observed for this human probiotic in antibiotic-associated diarrhea. PMID- 27001811 TI - Dalbavancin Activity When Tested against Streptococcus pneumoniae Isolated in Medical Centers on Six Continents (2011 to 2014). AB - Dalbavancin, a novel lipoglycopeptide, was approved for use in 2014 by regulatory agencies in the United States and Europe for the treatment of skin and skin structure infections. The activity of dalbavancin was also widely assessed by determination of its activity against Streptococcus pneumoniae clinical isolates collected from patients on six continents monitored during two time intervals (2011 to 2013 and 2014). A total of 18,186 pneumococcal isolates were obtained from 49 nations and submitted to a monitoring laboratory as part of the SENTRY Antimicrobial Surveillance Program for reference susceptibility testing. The potency of dalbavancin against S. pneumoniae was consistent across the years that it was monitored, with the MIC50 and MIC90 being 0.015 and 0.03 MUg/ml, respectively, and all isolates were inhibited by <=0.12 MUg/ml. The activity of dalbavancin was not adversely influenced by nonsusceptibility to beta-lactams (ceftriaxone or penicillin), macrolides, clindamycin, fluoroquinolones, or tetracyclines or multidrug resistance (MDR). Regional variations in dalbavancin activity were not detected, but S. pneumoniae strains isolated in the Asia Pacific region were more likely to be nonsusceptible to penicillin and ceftriaxone as well as to be MDR than strains isolated in North or South America and Europe. Direct comparisons of potency illustrated that dalbavancin (MIC50 and MIC90, 0.015 and 0.03 MUg/ml, respectively) was 16-fold or more active than vancomycin (MIC50, 0.25 MUg/ml), linezolid (MIC50, 1 MUg/ml), levofloxacin (MIC50, 1 MUg/ml), ceftriaxone (MIC90, 1 MUg/ml), and penicillin (MIC90, 2 MUg/ml). In conclusion, dalbavancin had potent and consistent activity against this contemporary (2011 to 2014) collection of S. pneumoniae isolates. PMID- 27001812 TI - In Vitro and In Vivo Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis. AB - Leishmaniasis is endemic in 98 countries and territories worldwide. The therapies available for leishmaniasis have serious side effects, thus prompting the search for new therapies. The present study investigated the antileishmanial activities of 2,3-diarylsubstituted quinoxaline derivatives against Leishmania amazonensis The antiproliferative activities of 6,7-dichloro-2,3-diphenylquinoxaline (LSPN329) and 2,3-di-(4-methoxyphenyl)-quinoxaline (LSPN331) against promastigotes and intracellular amastigotes were assessed, and the cytotoxicities of LSPN329 and LSPN331 were determined. Morphological and ultrastructural alterations were examined by electron microscopy, and biochemical alterations, reflected by the mitochondrial membrane potential (DeltaPsim), mitochondrial superoxide anion (O2.(-)) concentration, the intracellular ATP concentration, cell volume, the level of phosphatidylserine exposure on the cell membrane, cell membrane integrity, and lipid inclusions, were evaluated. In vivo antileishmanial activity was evaluated in a murine cutaneous leishmaniasis model. Compounds LSPN329 and LSPN331 showed significant selectivity for promastigotes and intracellular amastigotes and low cytotoxicity. In promastigotes, ultrastructural alterations were observed, including an increase in lipid inclusions, concentric membranes, and intense mitochondrial swelling, which were associated with hyperpolarization of DeltaPsim, an increase in the O2.(-) concentration, decreased intracellular ATP levels, and a decrease in cell volume. Phosphatidylserine exposure and DNA fragmentation were not observed. The cellular membrane remained intact after treatment. Thus, the multifactorial response that was responsible for the cellular collapse of promastigotes was based on intense mitochondrial alterations. BALB/c mice treated with LSPN329 or LSPN331 showed a significant decrease in lesion thickness in the infected footpad. Therefore, the antileishmanial activity and mitochondrial mechanism of action of LSPN329 and LSPN331 and the decrease in lesion thickness in vivo brought about by LSPN329 and LSPN331 make them potential candidates for new drug development for the treatment of leishmaniasis. PMID- 27001813 TI - Inhibitory Potential of Antifungal Drugs on ATP-Binding Cassette Transporters P Glycoprotein, MRP1 to MRP5, BCRP, and BSEP. AB - Inhibition of ABC transporters is a common mechanism underlying drug-drug interactions (DDIs). We determined the inhibitory potential of antifungal drugs currently used for invasive fungal infections on ABC transporters P-glycoprotein (P-gp), MRP1 to MRP5, BCRP, and BSEP in vitro Membrane vesicles isolated from transporter-overexpressing HEK 293 cells were used to investigate the inhibitory potential of antifungal drugs (250 MUM) on transport of model substrates. Concentration-inhibition curves were determined if transport inhibition was >60%. Fifty percent inhibitory concentrations (IC50s) for P-gp and BCRP were both 2 MUM for itraconazole, 5 and 12 MUM for hydroxyitraconazole, 3 and 6 MUM for posaconazole, and 3 and 11 MUM for isavuconazole, respectively. BSEP was strongly inhibited by itraconazole and hydroxyitraconazole (3 and 17 MUM, respectively). Fluconazole and voriconazole did not inhibit any transport for >60%. Micafungin uniquely inhibited all transporters, with strong inhibition of MRP4 (4 MUM). Anidulafungin and caspofungin showed strong inhibition of BCRP (7 and 6 MUM, respectively). Amphotericin B only weakly inhibited BCRP-mediated transport (127 MUM). Despite their wide range of DDIs, azole antifungals exhibit selective inhibition on efflux transporters. Although echinocandins display low potential for clinically relevant DDIs, they demonstrate potent in vitro inhibitory activity. This suggests that inhibition of ABC transporters plays a crucial role in the inexplicable (non-cytochrome P450-mediated) DDIs with antifungal drugs. PMID- 27001814 TI - Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies. AB - The emergence and spread of artemisinin-resistant Plasmodium falciparum is of huge concern for the global effort toward malaria control and elimination. Artemisinin resistance, defined as a delayed time to parasite clearance following administration of artemisinin, is associated with mutations in the Pfkelch13 gene of resistant parasites. To date, as many as 60 nonsynonymous mutations have been identified in this gene, but whether these mutations have been selected by artemisinin usage or merely reflect natural polymorphism independent of selection is currently unknown. To clarify this, we sequenced the Pfkelch13 propeller domain in 581 isolates collected before (420 isolates) and after (161 isolates) the implementation of artemisinin combination therapies (ACTs), from various regions of endemicity worldwide. Nonsynonymous mutations were observed in 1% of parasites isolated prior to the introduction of ACTs. Frequencies of mutant isolates, nucleotide diversity, and haplotype diversity were significantly higher in the parasites isolated from populations exposed to artemisinin than in those from populations that had not been exposed to the drug. In the artemisinin exposed population, a significant excess of dN compared to dS was observed, suggesting the presence of positive selection. In contrast, pairwise comparison of dN and dS and the McDonald and Kreitman test indicate that purifying selection acts on the Pfkelch13 propeller domain in populations not exposed to ACTs. These population genetic analyses reveal a low baseline of Pfkelch13 polymorphism, probably due to purifying selection in the absence of artemisinin selection. In contrast, various Pfkelch13 mutations have been selected under artemisinin pressure. PMID- 27001815 TI - Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients. AB - The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the use of at least one drug that resulted in a severe DDI. The findings of this study demonstrate that a majority of hospitalized patients receiving MAT are at risk for severe drug-drug interactions and highlight the need for antifungal stewardship. PMID- 27001816 TI - Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease. AB - Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-gamma], interleukin 4 [IL-4], and MIP1 alpha), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy. PMID- 27001817 TI - Candida albicans Airway Colonization Facilitates Subsequent Acinetobacter baumannii Pneumonia in a Rat Model. AB - The objective of the study was to determine the effects of Candida albicans respiratory tract colonization on Acinetobacter baumannii pneumonia in a rat model. Rats were colonized with C. albicans by instillation of 3 * 10(6) CFU into their airways, while sterile saline was instilled in the control group. The colonized rats were further divided into two groups: treated with amphotericin B or not. The rats were subsequently infected with A. baumannii (10(8) CFU by tracheobronchial instillation). A. baumannii lung CFU counts, cytokine lung levels, and rates of A. baumannii pneumonia were compared between groups. In vitro expression of A. baumannii virulence genes was measured by reverse transcription (RT)-PCR after 24-hour incubation with C. albicans or with Mueller Hinton (MH) broth alone. Rats with Candida colonization developed A. baumannii pneumonia more frequently and had higher A. baumannii CFU burdens and heavier lungs than controls. After A. baumannii infection, lung interleukin 17 (IL-17) concentrations were lower and gamma interferon (IFN-gamma) concentrations were higher in Candida-colonized rats than in controls. Candida-colonized rats treated with amphotericin B had a decreased rate of A. baumannii pneumonia and lower IFN gamma levels but higher IL-17 levels than untreated rats. Expression of basC, barB, bauA, ptk, plc2, and pld2 was induced while expression of ompA and abaI was suppressed in A. baumannii cultured in the presence of C. albicans C. albicans colonization facilitated the development of A. baumannii pneumonia in a rat model. Among Candida-colonized rats, antifungal treatment lowered the incidence of A. baumannii pneumonia. These findings could be due to modification of the host immune response and/or expression of A. baumannii virulence genes by Candida spp. PMID- 27001818 TI - Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure. AB - Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants. PMID- 27001819 TI - Effects of Saline, an Ambient Acidic Environment, and Sodium Salicylate on OXA Mediated Carbapenem Resistance in Acinetobacter baumannii. AB - Different physiological conditions, such as NaCl, low pH, and sodium salicylate, have been shown to affect antibiotic resistance determinants in Acinetobacter baumannii isolates. Therefore, the aim of this study was to investigate the effects of NaCl, sodium salicylate, and low pH on the susceptibility of A. baumannii to carbapenem. We cloned genes encoding oxacillinases (OXA) of different subclasses, with their associated promoters, from carbapenem-resistant A. baumannii isolates into the same vector and transferred them to the A. baumannii reference strains ATCC 19606 and ATCC 17978. Carbapenem MICs were determined at least in triplicate by agar dilution under standard conditions, as well as in the presence of 200 mM NaCl or 16 mM sodium salicylate, or at pH 5.8. OXA-58-like gene expression was determined by reverse transcription-quantitative PCR (qRT-PCR). Under some experimental conditions, significant MIC reductions were shown for some transformants but not for others. Only in one instance were all transformants harboring the same OXA affected by the same condition: at pH 5.8, the imipenem and meropenem MICs for strains expressing OXA-58-like enzymes decreased from a resistant level (32 to 64 mg/liter) to an intermediate susceptible level (8 mg/liter). However, blaOXA-58-like gene expression remained the same. MICs for both wild-type reference strains were not affected by the conditions tested. Our results indicate that the effects of the experimental conditions tested on OXA in vivo are mostly strain dependent. MICs were not reduced to wild-type levels, suggesting that the conditions tested do not lead to complete OXA inhibition in the bacterial cell. PMID- 27001820 TI - Pharmacokinetics-Pharmacodynamics of a Novel beta-Lactamase Inhibitor, CB-618, in Combination with Meropenem in an In Vitro Infection Model. AB - The usefulness of beta-lactam antimicrobial agents is threatened as never before by beta-lactamase-producing bacteria. For this reason, there has been renewed interest in the development of broad-spectrum beta-lactamase inhibitors. Herein we describe the results of dose fractionation and dose-ranging studies carried out using a one-compartment in vitro infection model to determine the exposure measure for CB-618, a novel beta-lactamase inhibitor, most predictive of the efficacy when given in combination with meropenem. The challenge panel included Enterobacteriaceae clinical isolates, which collectively produced a wide range of beta-lactamase enzymes (KPC-2, KPC-3, FOX-5, OXA-48, SHV-11, SHV-27, and TEM-1). Human concentration-time profiles were simulated for each drug, and samples were collected for drug concentration and bacterial density determinations. Using data from dose fractionation studies and a challenge Klebsiella pneumoniae isolate (CB 618-potentiated meropenem MIC = 1 mg/liter), relationships between change from baseline in log10 CFU/ml at 24 h and each of CB-618 area under the concentration time curve over 24 h (AUC0-24), maximum concentration (Cmax), and percentage of the dosing interval that CB-618 concentrations remained above a given threshold were evaluated in combination with meropenem at 2 g every 8 h (q8h). The exposure measures most closely associated with CB-618 efficacy in combination with meropenem were the CB-618 AUC0-24 (r(2) = 0.835) and Cmax (r(2) = 0.826). Using the CB-618 AUC0-24 indexed to the CB-618-potentiated meropenem MIC value, the relationship between change from baseline in log10 CFU/ml at 24 h and CB-618 AUC0 24/MIC ratio in combination with meropenem was evaluated using the pooled data from five challenge isolates; the CB-618 AUC0-24/MIC ratio associated with net bacterial stasis and the 1- and 2-log10 CFU/ml reductions from baseline at 24 h were 27.3, 86.1, and 444.8, respectively. These data provide a pharmacokinetics pharmacodynamics (PK-PD) basis for evaluating potential CB-618 dosing regimens in combination with meropenem in future studies. PMID- 27001821 TI - Advanced Molecular Detection of Malarone Resistance. AB - The rapid emergence of drug-resistant malaria parasites during the course of an infection remains a major challenge for providing accurate treatment guidelines. This is particularly important in cases of malaria treatment failure. Using a previously well-characterized case of malaria treatment failure, we show the utility of using next-generation sequencing for early detection of the rise and selection of a previously reported atovaquone-proguanil (malarone) drug resistance-associated mutation. PMID- 27001822 TI - Successful Salvage of Central Venous Catheters in Patients with Catheter-Related or Central Line-Associated Bloodstream Infections by Using a Catheter Lock Solution Consisting of Minocycline, EDTA, and 25% Ethanol. AB - In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line associated bloodstream infections (CLABSI) while retaining the catheter in situ Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.). PMID- 27001824 TI - Successful Surgical Treatment of an Electrical Storm in a Patient With Atypical Noncompaction Cardiomyopathy. PMID- 27001823 TI - Oritavancin Activity Tested against Molecularly Characterized Staphylococci and Enterococci Displaying Elevated Linezolid MIC Results. AB - Oritavancin (MIC50/90, 0.03/0.06 to 0.12 MUg/ml) had potent activity against linezolid-resistant staphylococci, as well as Enterococcus faecalis and Enterococcus faecium (oritavancin MIC50/90, 0.015/0.12 MUg/ml against both species). All linezolid-resistant isolates were inhibited by oritavancin at <=0.12 MUg/ml. These results confirmed the absence of cross-resistance between linezolid and oritavancin in staphylococci and enterococci. PMID- 27001825 TI - Combgap contributes to recruitment of Polycomb group proteins in Drosophila. AB - Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as "Polycomb response elements" (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms. PMID- 27001826 TI - Behavioral contagion during learning about another agent's risk-preferences acts on the neural representation of decision-risk. AB - Our attitude toward risk plays a crucial role in influencing our everyday decision-making. Despite its importance, little is known about how human risk preference can be modulated by observing risky behavior in other agents at either the behavioral or the neural level. Using fMRI combined with computational modeling of behavioral data, we show that human risk-preference can be systematically altered by the act of observing and learning from others' risk related decisions. The contagion is driven specifically by brain regions involved in the assessment of risk: the behavioral shift is implemented via a neural representation of risk in the caudate nucleus, whereas the representations of other decision-related variables such as expected value are not affected. Furthermore, we uncover neural computations underlying learning about others' risk-preferences and describe how these signals interact with the neural representation of risk in the caudate. Updating of the belief about others' preferences is associated with neural activity in the dorsolateral prefrontal cortex (dlPFC). Functional coupling between the dlPFC and the caudate correlates with the degree of susceptibility to the contagion effect, suggesting that a frontal-subcortical loop, the so-called dorsolateral prefrontal-striatal circuit, underlies the modulation of risk-preference. Taken together, these findings provide a mechanistic account for how observation of others' risky behavior can modulate an individual's own risk-preference. PMID- 27001828 TI - Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2. AB - The lysosomal integral membrane protein type-2 (LIMP-2) plays a pivotal role in the delivery of beta-glucocerebrosidase (GC) to lysosomes. Mutations in GC result in Gaucher's disease (GD) and are the major genetic risk factor for the development of Parkinson's disease (PD). Variants in the LIMP-2 gene cause action myoclonus-renal failure syndrome and also have been linked to PD. Given the importance of GC and LIMP-2 in disease pathogenesis, we studied their interaction sites in more detail. Our previous data demonstrated that the crystal structure of LIMP-2 displays a hydrophobic three-helix bundle composed of helices 4, 5, and 7, of which helix 5 and 7 are important for ligand binding. Here, we identified a similar helical motif in GC through surface potential analysis. Coimmunoprecipitation and immunofluorescence studies revealed a triple-helical interface region within GC as critical for LIMP-2 binding and lysosomal transport. Based on these findings, we generated a LIMP-2 helix 5-derived peptide that precipitated and activated recombinant wild-type and GD-associated N370S mutant GC in vitro. The helix 5 peptide fused to a cell-penetrating peptide also activated endogenous lysosomal GC and reduced alpha-synuclein levels, suggesting that LIMP-2-derived peptides can be used to activate endogenous as well as recombinant wild-type or mutant GC efficiently. Our data also provide a structural model of the LIMP-2/GC complex that will facilitate the development of GC chaperones and activators as potential therapeutics for GD, PD, and related synucleinopathies. PMID- 27001829 TI - Ancient lipids document continuity in the use of early hunter-gatherer pottery through 9,000 years of Japanese prehistory. AB - The earliest pots in the world are from East Asia and date to the Late Pleistocene. However, ceramic vessels were only produced in large numbers during the warmer and more stable climatic conditions of the Holocene. It has long been assumed that the expansion of pottery was linked with increased sedentism and exploitation of new resources that became available with the ameliorated climate, but this hypothesis has never been tested. Through chemical analysis of their contents, we herein investigate the use of pottery across an exceptionally long 9,000-y sequence from the Jomon site of Torihama in western Japan, intermittently occupied from the Late Pleistocene to the mid-Holocene. Molecular and isotopic analyses of lipids from 143 vessels provides clear evidence that pottery across this sequence was predominantly used for cooking marine and freshwater resources, with evidence for diversification in the range of aquatic products processed during the Holocene. Conversely, there is little indication that ruminant animals or plants were processed in pottery, although it is evident from the faunal and macrobotanical remains that these foods were heavily exploited. Supported by other residue analysis data from Japan, our results show that the link between pottery and fishing was established in the Late Paleolithic and lasted well into the Holocene, despite environmental and socio-economic change. Cooking aquatic products in pottery represents an enduring social aspect of East Asian hunter gatherers, a tradition based on a dependable technology for exploiting a sustainable resource in an uncertain and changing world. PMID- 27001827 TI - Neural basis of reward anticipation and its genetic determinants. AB - Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature. PMID- 27001830 TI - Spatial landmarks regulate a Cdc42-dependent MAPK pathway to control differentiation and the response to positional compromise. AB - A fundamental problem in cell biology is to understand how spatial information is recognized and integrated into morphogenetic responses. Budding yeast undergoes differentiation to filamentous growth, which involves changes in cell polarity through mechanisms that remain obscure. Here we define a regulatory input where spatial landmarks (bud-site-selection proteins) regulate the MAPK pathway that controls filamentous growth (fMAPK pathway). The bud-site GTPase Rsr1p regulated the fMAPK pathway through Cdc24p, the guanine nucleotide exchange factor for the polarity establishment GTPase Cdc42p. Positional landmarks that direct Rsr1p to bud sites conditionally regulated the fMAPK pathway, corresponding to their roles in regulating bud-site selection. Therefore, cell differentiation is achieved in part by the reorganization of polarity at bud sites. In line with this conclusion, dynamic changes in budding pattern during filamentous growth induced corresponding changes in fMAPK activity. Intrinsic compromise of bud-site selection also impacted fMAPK activity. Therefore, a surveillance mechanism monitors spatial position in response to extrinsic and intrinsic stress and modulates the response through a differentiation MAPK pathway. PMID- 27001832 TI - Correction for Roberts et al., Continuity of mammalian fauna over the last 200,000 y in the Indian subcontinent. PMID- 27001833 TI - Correction for Rodrigues et al., Biophysical principles predict fitness landscapes of drug resistance. PMID- 27001831 TI - Identification of three LRR-RKs involved in perception of root meristem growth factor in Arabidopsis. AB - A peptide hormone, root meristem growth factor (RGF), regulates root meristem development through the PLETHORA (PLT) stem cell transcription factor pathway, but it remains to be uncovered how extracellular RGF signals are transduced to the nucleus. Here we identified, using a combination of a custom-made receptor kinase (RK) expression library and exhaustive photoaffinity labeling, three leucine-rich repeat RKs (LRR-RKs) that directly interact with RGF peptides in Arabidopsis These three LRR-RKs, which we named RGFR1, RGFR2, and RGFR3, are expressed in root tissues including the proximal meristem, the elongation zone, and the differentiation zone. The triple rgfr mutant was insensitive to externally applied RGF peptide and displayed a short root phenotype accompanied by a considerable decrease in meristematic cell number. In addition, PLT1 and PLT2 protein gradients, observed as a gradual gradient decreasing toward the elongation zone from the stem cell area in wild type, steeply declined at the root tip in the triple mutant. Because RGF peptides have been shown to create a diffusion-based concentration gradient extending from the stem cell area, our results strongly suggest that RGFRs mediate the transformation of an RGF peptide gradient into a PLT protein gradient in the proximal meristem, thereby acting as key regulators of root meristem development. PMID- 27001834 TI - Manipulating spin-polarized photocurrents in 2D transition metal dichalcogenides. AB - Manipulating spin polarization of electrons in nonmagnetic semiconductors by means of electric fields or optical fields is an essential theme of the conceptual nonmagnetic semiconductor-based spintronics. Here we experimentally demonstrate an electric method of detecting spin polarization in monolayer transition metal dichalcogenides (TMDs) generated by circularly polarized optical pumping. The spin-polarized photocurrent is achieved through the valley-dependent optical selection rules and the spin-valley locking in monolayer WS2, and electrically detected by a lateral spin-valve structure with ferromagnetic contacts. The demonstrated long spin-valley lifetime, the unique valley contrasted physics, and the spin-valley locking make monolayer WS2 an unprecedented candidate for semiconductor-based spintronics. PMID- 27001835 TI - Biosynthesis of coral settlement cue tetrabromopyrrole in marine bacteria by a uniquely adapted brominase-thioesterase enzyme pair. AB - Halogenated pyrroles (halopyrroles) are common chemical moieties found in bioactive bacterial natural products. The halopyrrole moieties of mono- and dihalopyrrole-containing compounds arise from a conserved mechanism in which a proline-derived pyrrolyl group bound to a carrier protein is first halogenated and then elaborated by peptidic or polyketide extensions. This paradigm is broken during the marine pseudoalteromonad bacterial biosynthesis of the coral larval settlement cue tetrabromopyrrole (1), which arises from the substitution of the proline-derived carboxylate by a bromine atom. To understand the molecular basis for decarboxylative bromination in the biosynthesis of 1, we sequenced two Pseudoalteromonas genomes and identified a conserved four-gene locus encoding the enzymes involved in its complete biosynthesis. Through total in vitro reconstitution of the biosynthesis of 1 using purified enzymes and biochemical interrogation of individual biochemical steps, we show that all four bromine atoms in 1 are installed by the action of a single flavin-dependent halogenase: Bmp2. Tetrabromination of the pyrrole induces a thioesterase-mediated offloading reaction from the carrier protein and activates the biosynthetic intermediate for decarboxylation. Insights into the tetrabrominating activity of Bmp2 were obtained from the high-resolution crystal structure of the halogenase contrasted against structurally homologous halogenase Mpy16 that forms only a dihalogenated pyrrole in marinopyrrole biosynthesis. Structure-guided mutagenesis of the proposed substrate-binding pocket of Bmp2 led to a reduction in the degree of halogenation catalyzed. Our study provides a biogenetic basis for the biosynthesis of 1 and sets a firm foundation for querying the biosynthetic potential for the production of 1 in marine (meta)genomes. PMID- 27001836 TI - PGE2 induced in and released by dying cells functions as an inhibitory DAMP. AB - Cellular components released into the external milieu as a result of cell death and sensed by the body are generally termed damage-associated molecular patterns (DAMPs). Although DAMPs are conventionally thought to be protective to the host by evoking inflammatory responses important for immunity and wound repair, there is the prevailing notion that dysregulated release of DAMPs can also underlie or exacerbate disease development. However, the critical issue for how resultant DAMP-mediated responses are regulated has heretofore not been fully addressed. In the present study, we identify prostaglandin E2 (PGE2) as a DAMP that negatively regulates immune responses. We show that the production of PGE2 is augmented under cell death-inducing conditions via the transcriptional induction of the cyclooxygenase 2 (COX2) gene and that cell-released PGE2 suppresses the expression of genes associated with inflammation, thereby limiting the cell's immunostimulatory activities. Consistent with this, inhibition of the PGE2 synthesis pathway potentiates the inflammation induced by dying cells. We also provide in vivo evidence for a protective role of PGE2 released upon acetaminophen-induced liver injury as well as a pathogenic role for PGE2 during tumor cell growth. Our study places this classically known lipid mediator in an unprecedented context-that is, an inhibitory DAMP vis-a-vis activating DAMPs, which may have translational implications for designing more effective therapeutic regimens for inflammation-associated diseases. PMID- 27001838 TI - Invasive species triggers a massive loss of ecosystem services through a trophic cascade. AB - Despite growing recognition of the importance of ecosystem services and the economic and ecological harm caused by invasive species, linkages between invasions, changes in ecosystem functioning, and in turn, provisioning of ecosystem services remain poorly documented and poorly understood. We evaluate the economic impacts of an invasion that cascaded through a food web to cause substantial declines in water clarity, a valued ecosystem service. The predatory zooplankton, the spiny water flea (Bythotrephes longimanus), invaded the Laurentian Great Lakes in the 1980s and has subsequently undergone secondary spread to inland lakes, including Lake Mendota (Wisconsin), in 2009. In Lake Mendota, Bythotrephes has reached unparalleled densities compared with in other lakes, decreasing biomass of the grazer Daphnia pulicaria and causing a decline in water clarity of nearly 1 m. Time series modeling revealed that the loss in water clarity, valued at US$140 million (US$640 per household), could be reversed by a 71% reduction in phosphorus loading. A phosphorus reduction of this magnitude is estimated to cost between US$86.5 million and US$163 million (US$430 US$810 per household). Estimates of the economic effects of Great Lakes invasive species may increase considerably if cases of secondary invasions into inland lakes, such as Lake Mendota, are included. Furthermore, such extreme cases of economic damages call for increased investment in the prevention and control of invasive species to better maximize the economic benefits of such programs. Our results highlight the need to more fully incorporate ecosystem services into our analysis of invasive species impacts, management, and public policy. PMID- 27001837 TI - Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in parkinsonism. AB - Midbrain dopaminergic neurons are essential for appropriate voluntary movement, as epitomized by the cardinal motor impairments arising in Parkinson's disease. Understanding the basis of such motor control requires understanding how the firing of different types of dopaminergic neuron relates to movement and how this activity is deciphered in target structures such as the striatum. By recording and labeling individual neurons in behaving mice, we show that the representation of brief spontaneous movements in the firing of identified midbrain dopaminergic neurons is cell-type selective. Most dopaminergic neurons in the substantia nigra pars compacta (SNc), but not in ventral tegmental area or substantia nigra pars lateralis, consistently represented the onset of spontaneous movements with a pause in their firing. Computational modeling revealed that the movement-related firing of these dopaminergic neurons can manifest as rapid and robust fluctuations in striatal dopamine concentration and receptor activity. The exact nature of the movement-related signaling in the striatum depended on the type of dopaminergic neuron providing inputs, the striatal region innervated, and the type of dopamine receptor expressed by striatal neurons. Importantly, in aged mice harboring a genetic burden relevant for human Parkinson's disease, the precise movement-related firing of SNc dopaminergic neurons and the resultant striatal dopamine signaling were lost. These data show that distinct dopaminergic cell types differentially encode spontaneous movement and elucidate how dysregulation of their firing in early Parkinsonism can impair their effector circuits. PMID- 27001839 TI - CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing. AB - Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24-48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors. PMID- 27001840 TI - Virological factors that increase the transmissibility of emerging human viruses. AB - The early detection of pathogens with epidemic potential is of major importance to public health. Most emerging infections result in dead-end "spillover" events in which a pathogen is transmitted from an animal reservoir to a human but is unable to achieve the sustained human-to-human transmission necessary for a full blown epidemic. It is therefore critical to determine why only some virus infections are efficiently transmitted among humans whereas others are not. We sought to determine which biological features best characterized those viruses that have achieved sustained human transmission. Accordingly, we compiled a database of 203 RNA and DNA human viruses and used an information theoretic approach to assess which of a set of key biological variables were the best predictors of human-to-human transmission. The variables analyzed were as follows: taxonomic classification; genome length, type, and segmentation; the presence or absence of an outer envelope; recombination frequency; duration of infection; host mortality; and whether or not a virus exhibits vector-borne transmission. This comparative analysis revealed multiple strong associations. In particular, we determined that viruses with low host mortality, that establish long-term chronic infections, and that are nonsegmented, nonenveloped, and, most importantly, not transmitted by vectors were more likely to be transmissible among humans. In contrast, variables including genome length, genome type, and recombination frequency had little predictive power. In sum, we have identified multiple biological features that seemingly determine the likelihood of interhuman viral transmissibility, in turn enabling general predictions of whether viruses of a particular type will successfully emerge in human populations. PMID- 27001841 TI - Revealing metallic ink in Herculaneum papyri. AB - Writing on paper is essential to civilization, as Pliny the Elder remarks in his Natural History, when he describes the various types of papyri, the method of manufacturing them, and all that concerns writing materials in the mid-first century AD. For this reason, a rigorous scientific study of writing is of fundamental importance for the historical understanding of ancient societies. We show that metallic ink was used several centuries earlier than previously thought. In particular, we found strong evidence that lead was intentionally used in the ink of Herculaneum papyri and discuss the possible existence of ruled lines traced on the papyrus texture. In addition, the metallic concentrations found in these fragments deliver important information in view of optimizing future computed tomography (CT) experiments on still-unrolled Herculaneum scrolls to improve the readability of texts in the only surviving ancient Greco-Roman library. PMID- 27001842 TI - Structural analysis of the dodecameric proteasome activator PafE in Mycobacterium tuberculosis. AB - The human pathogen Mycobacterium tuberculosis (Mtb) requires a proteasome system to cause lethal infections in mice. We recently found that proteasome accessory factor E (PafE, Rv3780) activates proteolysis by the Mtb proteasome independently of adenosine triphosphate (ATP). Moreover, PafE contributes to the heat-shock response and virulence of Mtb Here, we show that PafE subunits formed four-helix bundles similar to those of the eukaryotic ATP-independent proteasome activator subunits of PA26 and PA28. However, unlike any other known proteasome activator, PafE formed dodecamers with 12-fold symmetry, which required a glycine-XXX glycine-XXX-glycine motif that is not found in previously described activators. Intriguingly, the truncation of the PafE carboxyl-terminus resulted in the robust binding of PafE rings to native proteasome core particles and substantially increased proteasomal activity, suggesting that the extended carboxyl-terminus of this cofactor confers suboptimal binding to the proteasome core particle. Collectively, our data show that proteasomal activation is not limited to hexameric ATPases in bacteria. PMID- 27001843 TI - Discovery of unfixed endogenous retrovirus insertions in diverse human populations. AB - Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from <0.0005 to >0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity. PMID- 27001845 TI - QnAs with Karl Deisseroth. PMID- 27001844 TI - Direction of information flow in large-scale resting-state networks is frequency dependent. AB - Normal brain function requires interactions between spatially separated, and functionally specialized, macroscopic regions, yet the directionality of these interactions in large-scale functional networks is unknown. Magnetoencephalography was used to determine the directionality of these interactions, where directionality was inferred from time series of beamformer reconstructed estimates of neuronal activation, using a recently proposed measure of phase transfer entropy. We observed well-organized posterior-to-anterior patterns of information flow in the higher-frequency bands (alpha1, alpha2, and beta band), dominated by regions in the visual cortex and posterior default mode network. Opposite patterns of anterior-to-posterior flow were found in the theta band, involving mainly regions in the frontal lobe that were sending information to a more distributed network. Many strong information senders in the theta band were also frequent receivers in the alpha2 band, and vice versa. Our results provide evidence that large-scale resting-state patterns of information flow in the human brain form frequency-dependent reentry loops that are dominated by flow from parieto-occipital cortex to integrative frontal areas in the higher frequency bands, which is mirrored by a theta band anterior-to-posterior flow. PMID- 27001846 TI - Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species. AB - Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ~12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation. PMID- 27001847 TI - Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5 mediated m6A-demethylation of NANOG mRNA. AB - N(6)-methyladenosine (m(6)A) modification of mRNA plays a role in regulating embryonic stem cell pluripotency. However, the physiological signals that determine the balance between methylation and demethylation have not been described, nor have studies addressed the role of m(6)A in cancer stem cells. We report that exposure of breast cancer cells to hypoxia stimulated hypoxia inducible factor (HIF)-1alpha- and HIF-2alpha-dependent expression of AlkB homolog 5 (ALKBH5), an m(6)A demethylase, which demethylated NANOG mRNA, which encodes a pluripotency factor, at an m(6)A residue in the 3'-UTR. Increased NANOG mRNA and protein expression, and the breast cancer stem cell (BCSC) phenotype, were induced by hypoxia in an HIF- and ALKBH5-dependent manner. Insertion of the NANOG 3'-UTR into a luciferase reporter gene led to regulation of luciferase activity by O2, HIFs, and ALKBH5, which was lost upon mutation of the methylated residue. ALKBH5 overexpression decreased NANOG mRNA methylation, increased NANOG levels, and increased the percentage of BCSCs, phenocopying the effect of hypoxia. Knockdown of ALKBH5 expression in MDA-MB-231 human breast cancer cells significantly reduced their capacity for tumor initiation as a result of reduced numbers of BCSCs. Thus, HIF-dependent ALKBH5 expression mediates enrichment of BCSCs in the hypoxic tumor microenvironment. PMID- 27001848 TI - Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. AB - Females have a greater immunological advantage than men, yet they are more prone to autoimmune disorders. The basis for this sex bias lies in the X chromosome, which contains many immunity-related genes. Female mammals use X chromosome inactivation (XCI) to generate a transcriptionally silent inactive X chromosome (Xi) enriched with heterochromatic modifications and XIST/Xist RNA, which equalizes gene expression between the sexes. Here, we examine the maintenance of XCI in lymphocytes from females in mice and humans. Strikingly, we find that mature naive T and B cells have dispersed patterns of XIST/Xist RNA, and they lack the typical heterochromatic modifications of the Xi. In vitro activation of lymphocytes triggers the return of XIST/Xist RNA transcripts and some chromatin marks (H3K27me3, ubiquitin-H2A) to the Xi. Single-cell RNA FISH analysis of female T cells revealed that the X-linked immunity genes CD40LG and CXCR3 are biallelically expressed in some cells. Using knockout and knockdown approaches, we find that Xist RNA-binding proteins, YY1 and hnRNPU, are critical for recruitment of XIST/Xist RNA back to the Xi. Furthermore, we examined B cells from patients with systemic lupus erythematosus, an autoimmune disorder with a strong female bias, and observed different XIST RNA localization patterns, evidence of biallelic expression of immunity-related genes, and increased transcription of these genes. We propose that the Xi in female lymphocytes is predisposed to become partially reactivated and to overexpress immunity-related genes, providing the first mechanistic evidence to our knowledge for the enhanced immunity of females and their increased susceptibility for autoimmunity. PMID- 27001849 TI - Convergence in the temperature response of leaf respiration across biomes and plant functional types. AB - Plant respiration constitutes a massive carbon flux to the atmosphere, and a major control on the evolution of the global carbon cycle. It therefore has the potential to modulate levels of climate change due to the human burning of fossil fuels. Neither current physiological nor terrestrial biosphere models adequately describe its short-term temperature response, and even minor differences in the shape of the response curve can significantly impact estimates of ecosystem carbon release and/or storage. Given this, it is critical to establish whether there are predictable patterns in the shape of the respiration-temperature response curve, and thus in the intrinsic temperature sensitivity of respiration across the globe. Analyzing measurements in a comprehensive database for 231 species spanning 7 biomes, we demonstrate that temperature-dependent increases in leaf respiration do not follow a commonly used exponential function. Instead, we find a decelerating function as leaves warm, reflecting a declining sensitivity to higher temperatures that is remarkably uniform across all biomes and plant functional types. Such convergence in the temperature sensitivity of leaf respiration suggests that there are universally applicable controls on the temperature response of plant energy metabolism, such that a single new function can predict the temperature dependence of leaf respiration for global vegetation. This simple function enables straightforward description of plant respiration in the land-surface components of coupled earth system models. Our cross-biome analyses shows significant implications for such fluxes in cold climates, generally projecting lower values compared with previous estimates. PMID- 27001851 TI - Analysis and valuation of the health and climate change cobenefits of dietary change. AB - What we eat greatly influences our personal health and the environment we all share. Recent analyses have highlighted the likely dual health and environmental benefits of reducing the fraction of animal-sourced foods in our diets. Here, we couple for the first time, to our knowledge, a region-specific global health model based on dietary and weight-related risk factors with emissions accounting and economic valuation modules to quantify the linked health and environmental consequences of dietary changes. We find that the impacts of dietary changes toward less meat and more plant-based diets vary greatly among regions. The largest absolute environmental and health benefits result from diet shifts in developing countries whereas Western high-income and middle-income countries gain most in per capita terms. Transitioning toward more plant-based diets that are in line with standard dietary guidelines could reduce global mortality by 6-10% and food-related greenhouse gas emissions by 29-70% compared with a reference scenario in 2050. We find that the monetized value of the improvements in health would be comparable with, or exceed, the value of the environmental benefits although the exact valuation method used considerably affects the estimated amounts. Overall, we estimate the economic benefits of improving diets to be 1-31 trillion US dollars, which is equivalent to 0.4-13% of global gross domestic product (GDP) in 2050. However, significant changes in the global food system would be necessary for regional diets to match the dietary patterns studied here. PMID- 27001850 TI - Functional identification of a neurocircuit regulating blood glucose. AB - Previous studies implicate the hypothalamic ventromedial nucleus (VMN) in glycemic control. Here, we report that selective inhibition of the subset of VMN neurons that express the transcription factor steroidogenic-factor 1 (VMN(SF1) neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMN(SF1) neurons causes diabetes-range hyperglycemia. Moreover, this hyperglycemic response is reproduced by selective activation of VMN(SF1) fibers projecting to the anterior bed nucleus of the stria terminalis (aBNST), but not to other brain areas innervated by VMN(SF1) neurons. We also report that neurons in the lateral parabrachial nucleus (LPBN), a brain area that is also implicated in the response to hypoglycemia, make synaptic connections with the specific subset of glucoregulatory VMN(SF1) neurons that project to the aBNST. These results collectively establish a physiological role in glucose homeostasis for VMN(SF1) neurons and suggest that these neurons are part of an ascending glucoregulatory LPBN->VMN(SF1)->aBNST neurocircuit. PMID- 27001852 TI - Invasive mammal eradication on islands results in substantial conservation gains. AB - More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List-6% of all these highly threatened species-likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna. PMID- 27001853 TI - Epigenome confrontation triggers immediate reprogramming of DNA methylation and transposon silencing in Arabidopsis thaliana F1 epihybrids. AB - Genes and transposons can exist in variable DNA methylation states, with potentially differential transcription. How these epialleles emerge is poorly understood. Here, we show that crossing an Arabidopsis thaliana plant with a hypomethylated genome and a normally methylated WT individual results, already in the F1 generation, in widespread changes in DNA methylation and transcription patterns. Novel nonparental and heritable epialleles arise at many genic loci, including a locus that itself controls DNA methylation patterns, but with most of the changes affecting pericentromeric transposons. Although a subset of transposons show immediate resilencing, a large number display decreased DNA methylation, which is associated with de novo or enhanced transcriptional activation and can translate into transposon mobilization in the progeny. Our findings reveal that the combination of distinct epigenomes can be viewed as an epigenomic shock, which is characterized by a round of epigenetic variation creating novel patterns of gene and TE regulation. PMID- 27001855 TI - Origin of low sodium capacity in graphite and generally weak substrate binding of Na and Mg among alkali and alkaline earth metals. AB - It is well known that graphite has a low capacity for Na but a high capacity for other alkali metals. The growing interest in alternative cation batteries beyond Li makes it particularly important to elucidate the origin of this behavior, which is not well understood. In examining this question, we find a quite general phenomenon: among the alkali and alkaline earth metals, Na and Mg generally have the weakest chemical binding to a given substrate, compared with the other elements in the same column of the periodic table. We demonstrate this with quantum mechanics calculations for a wide range of substrate materials (not limited to C) covering a variety of structures and chemical compositions. The phenomenon arises from the competition between trends in the ionization energy and the ion-substrate coupling, down the columns of the periodic table. Consequently, the cathodic voltage for Na and Mg is expected to be lower than those for other metals in the same column. This generality provides a basis for analyzing the binding of alkali and alkaline earth metal atoms over a broad range of systems. PMID- 27001856 TI - Phase transitions in semidefinite relaxations. AB - Statistical inference problems arising within signal processing, data mining, and machine learning naturally give rise to hard combinatorial optimization problems. These problems become intractable when the dimensionality of the data is large, as is often the case for modern datasets. A popular idea is to construct convex relaxations of these combinatorial problems, which can be solved efficiently for large-scale datasets. Semidefinite programming (SDP) relaxations are among the most powerful methods in this family and are surprisingly well suited for a broad range of problems where data take the form of matrices or graphs. It has been observed several times that when the statistical noise is small enough, SDP relaxations correctly detect the underlying combinatorial structures. In this paper we develop asymptotic predictions for several detection thresholds, as well as for the estimation error above these thresholds. We study some classical SDP relaxations for statistical problems motivated by graph synchronization and community detection in networks. We map these optimization problems to statistical mechanics models with vector spins and use nonrigorous techniques from statistical mechanics to characterize the corresponding phase transitions. Our results clarify the effectiveness of SDP relaxations in solving high dimensional statistical problems. PMID- 27001854 TI - Club cells surviving influenza A virus infection induce temporary nonspecific antiviral immunity. AB - A brief window of antigen-nonspecific protection has been observed after influenza A virus (IAV) infection. Although this temporary immunity has been assumed to be the result of residual nonspecific inflammation, this period of induced immunity has not been fully studied. Because IAV has long been characterized as a cytopathic virus (based on its ability to rapidly lyse most cell types in culture), it has been a forgone conclusion that directly infected cells could not be contributing to this effect. Using a Cre recombinase expressing IAV, we have previously shown that club cells can survive direct viral infection. We show here not only that these cells can eliminate all traces of the virus and survive but also that they acquire a heightened antiviral response phenotype after surviving. Moreover, we experimentally demonstrate temporary nonspecific viral immunity after IAV infection and show that surviving cells are required for this phenotype. This work characterizes a virally induced modulation of the innate immune response that may represent a new mechanism to prevent viral diseases. PMID- 27001858 TI - Cell-specific localization of alkaloids in Catharanthus roseus stem tissue measured with Imaging MS and Single-cell MS. AB - Catharanthus roseus (L.) G. Don is a medicinal plant well known for producing antitumor drugs such as vinblastine and vincristine, which are classified as terpenoid indole alkaloids (TIAs). The TIA metabolic pathway in C. roseus has been extensively studied. However, the localization of TIA intermediates at the cellular level has not been demonstrated directly. In the present study, the metabolic pathway of TIA in C. roseus was studied with two forefront metabolomic techniques, that is, Imaging mass spectrometry (MS) and live Single-cell MS, to elucidate cell-specific TIA localization in the stem tissue. Imaging MS indicated that most TIAs localize in the idioblast and laticifer cells, which emit blue fluorescence under UV excitation. Single-cell MS was applied to four different kinds of cells [idioblast (specialized parenchyma cell), laticifer, parenchyma, and epidermal cells] in the stem longitudinal section. Principal component analysis of Imaging MS and Single-cell MS spectra of these cells showed that similar alkaloids accumulate in both idioblast cell and laticifer cell. From MS/MS analysis of Single-cell MS spectra, catharanthine, ajmalicine, and strictosidine were found in both cell types in C. roseus stem tissue, where serpentine was also accumulated. Based on these data, we discuss the significance of TIA synthesis and accumulation in the idioblast and laticifer cells of C. roseus stem tissue. PMID- 27001857 TI - Suramin inhibits cullin-RING E3 ubiquitin ligases. AB - Cullin-RING E3 ubiquitin ligases (CRL) control a myriad of biological processes by directing numerous protein substrates for proteasomal degradation. Key to CRL activity is the recruitment of the E2 ubiquitin-conjugating enzyme Cdc34 through electrostatic interactions between E3's cullin conserved basic canyon and the acidic C terminus of the E2 enzyme. This report demonstrates that a small molecule compound, suramin, can inhibit CRL activity by disrupting its ability to recruit Cdc34. Suramin, an antitrypansomal drug that also possesses antitumor activity, was identified here through a fluorescence-based high-throughput screen as an inhibitor of ubiquitination. Suramin was shown to target cullin 1's conserved basic canyon and to block its binding to Cdc34. Suramin inhibits the activity of a variety of CRL complexes containing cullin 2, 3, and 4A. When introduced into cells, suramin induced accumulation of CRL substrates. These observations help develop a strategy of regulating ubiquitination by targeting an E2-E3 interface through small-molecule modulators. PMID- 27001859 TI - Structural basis of rifampin inactivation by rifampin phosphotransferase. AB - Rifampin (RIF) is a first-line drug used for the treatment of tuberculosis and other bacterial infections. Various RIF resistance mechanisms have been reported, and recently an RIF-inactivation enzyme, RIF phosphotransferase (RPH), was reported to phosphorylate RIF at its C21 hydroxyl at the cost of ATP. However, the underlying molecular mechanism remained unknown. Here, we solve the structures of RPH from Listeria monocytogenes (LmRPH) in different conformations. LmRPH comprises three domains: an ATP-binding domain (AD), an RIF-binding domain (RD), and a catalytic His-containing domain (HD). Structural analyses reveal that the C-terminal HD can swing between the AD and RD, like a toggle switch, to transfer phosphate. In addition to its catalytic role, the HD can bind to the AD and induce conformational changes that stabilize ATP binding, and the binding of the HD to the RD is required for the formation of the RIF-binding pocket. A line of hydrophobic residues forms the RIF-binding pocket and interacts with the 1 amino, 2-naphthol, 4-sulfonic acid and naphthol moieties of RIF. The R group of RIF points toward the outside of the pocket, explaining the low substrate selectivity of RPH. Four residues near the C21 hydroxyl of RIF, His825, Arg666, Lys670, and Gln337, were found to play essential roles in the phosphorylation of RIF; among these the His825 residue may function as the phosphate acceptor and donor. Our study reveals the molecular mechanism of RIF phosphorylation catalyzed by RPH and will guide the development of a new generation of rifamycins. PMID- 27001860 TI - Photochemical reaction cycle transitions during anion channelrhodopsin gating. AB - A recently discovered family of natural anion channelrhodopsins (ACRs) have the highest conductance among channelrhodopsins and exhibit exclusive anion selectivity, which make them efficient inhibitory tools for optogenetics. We report analysis of flash-induced absorption changes in purified wild-type and mutant ACRs, and of photocurrents they generate in HEK293 cells. Contrary to cation channelrhodopsins (CCRs), the ion conducting state of ACRs develops in an L-like intermediate that precedes the deprotonation of the retinylidene Schiff base (i.e., formation of an M intermediate). Channel closing involves two mechanisms leading to depletion of the conducting L-like state: (i) Fast closing is caused by a reversible L<=>M conversion. Glu-68 in Guillardia theta ACR1 plays an important role in this transition, likely serving as a counterion and proton acceptor at least at high and neutral pH. Incomplete suppression of M formation in the GtACR1_E68Q mutant indicates the existence of an alternative proton acceptor. (ii) Slow closing of the channel parallels irreversible depletion of the M-like and, hence, L-like state. Mutation of Cys-102 that strongly affected slow channel closing slowed the photocycle to the same extent. The L and M intermediates were in equilibrium in C102A as in the WT. In the position of Glu 123 in channelrhodopsin-2, ACRs contain a noncarboxylate residue, the mutation of which to Glu produced early Schiff base proton transfer and strongly inhibited channel activity. The data reveal fundamental differences between natural ACR and CCR conductance mechanisms and their underlying photochemistry, further confirming that these proteins form distinct families of rhodopsin channels. PMID- 27001863 TI - Swallow (deglutition) syncope. PMID- 27001862 TI - Alfred Gilman: Intrepid, committed scientist. PMID- 27001864 TI - Preparing clinicians for genomic medicine. PMID- 27001861 TI - Spatiotemporal dynamics of auditory attention synchronize with speech. AB - Attention plays a fundamental role in selectively processing stimuli in our environment despite distraction. Spatial attention induces increasing and decreasing power of neural alpha oscillations (8-12 Hz) in brain regions ipsilateral and contralateral to the locus of attention, respectively. This study tested whether the hemispheric lateralization of alpha power codes not just the spatial location but also the temporal structure of the stimulus. Participants attended to spoken digits presented to one ear and ignored tightly synchronized distracting digits presented to the other ear. In the magnetoencephalogram, spatial attention induced lateralization of alpha power in parietal, but notably also in auditory cortical regions. This alpha power lateralization was not maintained steadily but fluctuated in synchrony with the speech rate and lagged the time course of low-frequency (1-5 Hz) sensory synchronization. Higher amplitude of alpha power modulation at the speech rate was predictive of a listener's enhanced performance of stream-specific speech comprehension. Our findings demonstrate that alpha power lateralization is modulated in tune with the sensory input and acts as a spatiotemporal filter controlling the read-out of sensory content. PMID- 27001865 TI - Triethylenetetramine modulates polyamine and energy metabolism and inhibits cancer cell proliferation. AB - Polyamine metabolism is an attractive anticancer drug target, since polyamines are absolutely required for cellular proliferation, and increased levels of polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) are associated with cancer. Triethylenetetramine (TETA) is a charge-deficient isosteric analogue of the polyamine spermidine (Spd) and a Cu(II)-chelating compound used for the treatment of Wilson's disease, and it has been implicated as a potential anticancer therapeutic drug. In the present study, we studied the effects of TETA in comparison with two other Cu(II)-chelators, D-penicillamine (PA) and tetrathiomolybdate (TTM), on polyamine metabolism in DU145 prostate carcinoma, MCF-7 breast carcinoma and JEG-3 choriocarcinoma cells. TETA induced antizyme, down-regulated ODC and inhibited [(14)C] Spd uptake. Moreover, it completely prevented alpha-difluoromethylornithine (DFMO)-induced increase in [(14)C] Spd uptake, and inhibited [(14)C] putrescine (Put) uptake and ODC activity in vivo Seven-day treatment of DU145 cells with TETA caused growth cessation by reducing intracellular polyamine levels and suppressing the formation of hypusinated eukaryotic translation initiation factor 5A (eIF5A). TETA or its N-acetylated metabolites also inhibited spermine (Spm), diamine and semicarbazide-sensitive amine oxidases and decreased the level of intracellular reactive oxygen species. Moreover, TETA inhibited the utilization of Put as energy source via the tricarboxylic acid (TCA) cycle, as indicated by decreased production of (14)CO2 from [(14)C] Put. These results indicate that TETA attacks multiple proven anticancer drug targets not attributed to copper chelation, which warrants further studies to reveal its potential in cancer chemoprevention and cure. PMID- 27001866 TI - Kinetic characterization and regulation of the human retinaldehyde dehydrogenase 2 enzyme during production of retinoic acid. AB - Retinoic acid (RA) is an important regulator of embryogenesis and tissue homoeostasis. Perturbation of RA signalling causes developmental disorders, osteoarthritis, schizophrenia and several types of tumours. RA is produced by oxidation of retinaldehyde from vitamin A. The main enzyme producing RA in the early embryo is retinaldehyde dehydrogenase 2 (RALDH2, ALDH1A2). In the present study we describe in depth the kinetic properties and regulation of the human RALDH2 (hRALDH2) enzyme. We show that this enzyme produces RA using in vivo and in vitro assays. We studied the naturally occurring all-trans-, 9-cis- and 13-cis retinaldehyde isomers as substrates of hRALDH2. Based on the values measured for the Michaelis-Menten constant Km and the maximal rate Vmax, in vitro hRALDH2 displays the same catalytic efficiency for their oxidation. We characterized two known inhibitors of the vertebrate RALDH2 and determined their kinetic parameters on hRALDH2. In addition, RA was studied as a possible inhibitor of hRALDH2 and a regulator of its activity. We show that hRALDH2 is not inhibited by its oxidation product, all-trans-RA, suggesting the absence of a negative feedback regulatory loop. Expression of the Raldh2 gene is known to be regulated by RA itself, suggesting that the main regulation of the hRALDH2 activity level is transcriptional. PMID- 27001867 TI - Re-examining high reliability: actively organising for safety. PMID- 27001868 TI - Robot-assisted low anterior resection in fifty-three consecutive patients: an Indian experience. AB - From December 2005 to December 2009, we performed 150 laparoscopic colorectal procedures. Based on this experience, we started offering robot-assisted colorectal surgery from December 2009. This study is a prospective evaluation of consecutive patients in order to study the technical feasibility and oncological outcome of robot-assisted low anterior resection. This investigation was conducted at a single minimal access surgery institute. Between December 2009 and December 2011, 53 consecutive patients with rectal adenocarcinoma underwent a robot-assisted low anterior resection (LAR) or ultralow anterior resection (ULAR) with total mesorectal excision (TME), using the standard da Vinci 'S' model. Patient demographics, mean operative time, mean postoperative hospital stay, blood loss, days to first flatus, resumption of oral feeds, urinary incontinence, and sexual dysfunction were studied. Surgical and pathological outcomes such as quality of TME, free circumferential margins, and number of lymph nodes dissected were also evaluated. Robot docking and undocking times were noted. Of the 53 patients, 41 were men and 12 were women. Their mean age was 66.7 years (range 37 90 years). The ASA grades were distributed as follows: ASA I 15 (28.3 %), ASA II 25 (47.16 %), ASA III 12 (22.64 %), ASA IV 1 (1.88 %). The mean operative time was 180 min (150-230 min) and the mean blood loss was 101.6 ml (50-300 ml). The robot docking time was 10 min (15-25 min) and the undocking time was 5 min (3-10 min). The mean hospital stay was 8 days (7-15 days). None of the patients was converted to either laparoscopic or open procedure. The longitudinal and circumferential margins were negative in all patients. Histopathological reports of 45 patients showed complete TME while 8 patients showed nearly complete TME. No repositioning of the robot was needed for splenic flexure mobilization, thus decreasing the operative time. Along with TME, even the splenic flexure mobilization was achieved through the same robotic ports without undocking the robot. Robot-assisted LAR and ULAR is technically feasible, and a complete TME is possible. PMID- 27001869 TI - Robotic-assisted radical parametrectomy in patients with malignant gynecological tumors. AB - We describe the operative technique of robotic-assisted laparoscopic radical parametrectomy and analyze perioperative data including adequacy of resections, pathology, and complications in our initial cases. A retrospective study was performed of seven patients with gynecological cancers involving the cervix who had previously been treated with simple hysterectomies and then underwent robotic assisted radical parametrectomies. Pathology from the initial hysterectomies and the radical parametrectomies was reviewed. Postoperative complications, operative times, estimated blood loss, and length of hospital stay were assessed. The upper part of the vagina, parametrial tissue, and bilateral pelvic lymph nodes of all seven patients who had undergone a previous simple hysterectomy were removed. The mean age was 56.4 (SD +/- 10.7) years. Diagnoses from hysterectomy specimens were invasive squamous carcinoma (n = 4), endometrial adenocarcinoma (n = 2), and clear-cell papillary adenocystic cervical carcinoma (n = 1). The median number of lymph nodes removed was 8 (min 4, max 29), and one patient had nodal metastasis. The mean operative time was 228.6 (SD +/- 38.9) min, estimated blood loss was 147 (SD +/- 58.2) ml, and length of hospital stay was five (SD +/- 2.3) days. One intraoperative complication (cystotomy) occurred and was successfully repaired. One postoperative fistula developed on postoperative day 10. This early experience demonstrates that the basic surgical and anatomical principles of radical parametrectomy can be applied to robotic-assisted laparoscopic surgery. Genitourinary fistulae are always a concern with this procedure, and minimization of electrocautery near the bladder and ureters may further reduce complications. PMID- 27001870 TI - Contribution of robotics to minimally invasive esophagectomy. AB - Robot-assisted surgery has the advantages of a three-dimensional view, versatility of instruments and better ergonomics. It allows fine dissection and difficult anastomoses in deep fields. Based on our experience, we try to define what are the main contributions of robotics to minimally invasive esophagectomy. From December 2009 to July 2012, we performed 24 minimally invasive esophagectomies (9 transhiatal, 5 Ivor-Lewis and 10 three-field), 16 of them robotically (8, 5 and 3, respectively). Eighteen patients (18/24 = 75 %) received neoadjuvant therapy. Nine patients (9/24 = 37.5 %) had symptomatic complications: 4 anastomotic leaks treated conservatively, one staple failure of the gastric plasty needing reoperation, one biliary peritonitis secondary to a gangrenous cholecystitis, one intrathoracic gastric migration after the only nonresectable case, one chylothorax and one patient with major cardiopulmonary complications. The median number of lymph nodes harvested was 12 +/- 7. Median length of stay was 14 +/- 13.5 days. Thirty-day mortality was nil. Complications were not related to the robot itself but to the complexity of both the technique and the patient. Although we found no advantages for the use of robotics during threefield minimally invasive esophagectomy, robotic mediastinal dissection during transhiatal esophagectomy can be performed safely under direct vision. Moreover, hand-sewn robotic-assisted technique in the prone position is promising and maybe the simplest way to carry out thoracic anastomosis during Ivor-Lewis esophagectomy. PMID- 27001872 TI - Robot-assisted laparoscopic radical prostatectomy using modular training programme in a private hospital. AB - The aim of the study was to demonstrate an efficacious robotic fellowship model that balances safety of patients, time efficiency and adequate training, in a private hospital. Sixty-four patients underwent robot-assisted laparoscopic radical prostatectomy using a 13-step modular training programme in a single private institute. The patients were compared with 64 consecutive patients operated on by the mentoring surgeon immediately prior to the implementation of the programme. The main parameters analysed included console time, total operating time, blood loss, positive surgical margin rate and postoperative complications. There was a marginal difference in mean console time (92.67 vs. 90.41 min; p = 0.02). Statistical difference disappeared when comparing mean total operating time (136.09 vs. 134.14 min; p = 0.16), mean blood loss (165 vs. 172 ml; p = 0.96) and margin positivity (8 vs. 13; p = 0.34). The trainee was able to complete significant numbers of modular training steps whilst maintaining momentum of the operation from the commencement of the fellowship programme. This study demonstrates that a comprehensive modular training programme in complicated robotic procedures could be implemented without compromising patient safety or time efficiency. PMID- 27001871 TI - Robotic-assisted surgery for the treatment of pelvic masses in pregnant patients: a series of four cases and literature review. AB - The purpose of this study was to assess the safety and feasibility of robotic assisted surgery for the treatment of a pelvic mass in gravid patients. We retrospectively reviewed the charts of all pregnant women who were diagnosed with a pelvic mass by individual obstetric physicians and referred to our gynecologic oncology service from January 2009 until March 2012; four patients were identified and treated with robotic-assisted surgery by the same group of gynecologic oncologists. The following patient data were collected: age, disease origin, histology, tumor size, gravid status at surgery, surgical procedure, intra- and postoperative surgical complications, and both maternal and fetal outcomes. The gynecologic lesions comprised an immature teratoma, a mucinous cystadenoma, a hemorrhagic cyst and an ovarian endometrioma; in each case, blood loss was minimal and no maternal or fetal intra-operative complications were encountered. All patients had normal, spontaneous vaginal deliveries at term. Robotic-assisted surgery for the treatment of pelvic masses in pregnant patients is ostensibly feasible and associated with favorable outcomes for both the patient and fetus. PMID- 27001873 TI - Robotic-assisted laparoscopic trachelectomy: a case series and review of surgical technique. AB - We present a retrospective case series of patients who underwent robotic-assisted laparoscopic trachelectomies from August 1, 2011 to August 30, 2012, with a description of the surgical technique for successful cervical removal. The patients, at the Department of Obstetrics and Gynecology, Division of Urogynecology and Minimally Invasive Surgery at Penn State Milton S. Hershey Medical Center, were identified using ICD-9 coding for robotic-assisted trachelectomy. Of the 180 patients who had robotic-assisted gynecologic surgery during the study period, eight underwent robotic-assisted laparoscopic trachelectomy. The patients' average age was 40.4 years, average parity was 1.5, and mean body mass index was 28. The time interval from initial surgery of supracervical hysterectomy to robotic-assisted trachelectomy was 4 years. Pre operative cervical cytology was negative in all patients. The average length of stay was one overnight admission. The primary indication for prior supracervical hysterectomy was dense pelvic adhesions, and the main indications for robotic assisted trachelectomy were pelvic pain due to endometriosis and cyclic vaginal bleeding. Surgical outcomes included minimal blood loss (<50 ml) and mean operative time of 1.15 h (74.88 min), without any immediate intra-operative or post-operative complications reported. Histopathology reports on all cervical specimens were normal. Adnexectomy is the most common concomitant procedure performed with trachelectomy. Robotic-assisted laparoscopic trachelectomy is a viable option for patients requesting a minimally invasive approach to cervical stump removal. PMID- 27001874 TI - A practical system for recording instrument interactions during live robotic surgery. AB - We have developed a system for measuring and recording the high-frequency vibrations that characterize instrument interactions during minimally invasive robotic surgery. Consisting of simple circuitry and a DVD recorder, this system is low-cost and easily implementable, requires no sterilization, and enables measurement of a validated, objective technical skill metric in both the simulated setting and the operating room. The vibration recordings of fourteen sleeve gastrectomies were processed by segmenting the operation into seven phases and calculating the root mean square (RMS) vibration within each phase. Statistical analysis showed that the observed differences match expectations drawn from knowledge of the operation, substantiating the premise that RMS vibration provides a good measure of the intensity of instrument interactions during live robotic surgery. PMID- 27001875 TI - Comparison of robotic-assisted and open radical cystectomy in a community-based, non-tertiary health care setting. AB - We examined the safety and feasibility of transitioning from open radical cystectomies to robotic-assisted laparoscopic cystectomies in a community-based, non-tertiary health care setting. A retrospective review and analysis of our most recent 14 unselected consecutive patients who underwent open cystectomy was compared to our first 14 unselected consecutive patients who underwent robotic assisted laparoscopic cystectomy. Perioperative and pathologic outcomes were reviewed to determine the safety and oncologic equivalence of the two procedures. From 2003 to 2010, 14 consecutive patients underwent an open cystectomy and from 2010 to 2012 another 14 consecutive patients underwent a robotic-assisted laparoscopic cystectomy. The operative time was significantly longer in the robotic group (6 h 23 min vs. 4 h 28 min; p < 0.05) and intraoperative blood loss was significantly lower compared with the open radical cystectomy (ORC) group (470 ml vs. 942 ml; p < 0.05). Regarding complications, 21 % of robotic-assisted radical cystectomy (RARC) patients experienced major complications versus 14 % of ORC patients. Overall, there was no statistically significant difference in complication rates or length of hospital stay between the ORC and RARC groups. No pathologic differences were noted between the two groups and lymph node counts were similar in the two groups, with the median numbers being 11.9 and 9.5 in RARC and ORC, respectively. RARC can be accomplished in a community-based, non tertiary health care setting without compromising perioperative or pathologic outcomes during the institution of this minimally invasive procedure. PMID- 27001876 TI - Multidisciplinary validation study of the da Vinci Skills Simulator: educational tool and assessment device. AB - Despite the increased dexterity and precision of robotic surgery, like any new surgical technology it is still associated with a learning curve that can impact patient outcomes. The use of surgical simulators outside of the operating room, in a low-stakes environment, has been shown to shorten such learning curves. We present a multidisciplinary validation study of a robotic surgery simulator, the da Vinci((r)) Skills Simulator (dVSS). Trainees and attending faculty from the University of Toronto, Departments of Surgery and Obstetrics and Gynecology (ObGyn), were recruited to participate in this validation study. All participants completed seven different exercises on the dVSS (Camera Targeting 1, Peg Board 1, Peg Board 2, Ring Walk 2, Match Board 1, Thread the Rings, Suture Sponge 1) and, using the da Vinci S Robot (dVR), completed two standardized skill tasks (Ring Transfer, Needle Passing). Participants were categorized as novice robotic surgeon (NRS) and experienced robotic surgeon (ERS) based on the number of robotic cases performed. Statistical analysis was conducted using independent T test and non-parametric Spearman's correlation. A total of 53 participants were included in the study: 27 urology, 13 ObGyn, and 13 thoracic surgery (Table 1). Most participants (89 %) either had no prior console experience or had performed <10 robotic cases, while one (2 %) had performed 10-20 cases and five (9 %) had performed >=20 robotic surgeries. The dVSS demonstrated excellent face and content validity and 97 and 86 % of participants agreed that it was useful for residency training and post-graduate training, respectively. The dVSS also demonstrated construct validity, with NRS performing significantly worse than ERS on most exercises with respect to overall score, time to completion, economy of motion, and errors (Table 2). Excellent concurrent validity was also demonstrated as dVSS scores for most exercises correlated with performance of the two standardized skill tasks using the dVR (Table 3). This multidisciplinary validation study of the dVSS provides excellent face, content, construct, and concurrent validity evidence, which supports its integrated use in a comprehensive robotic surgery training program, both as an educational tool and potentially as an assessment device. Table 1 dVSS validation study participant demographic information Survey question Response Number (%) Gender Male 36 (67.9) Female 17 (32.1) Handedness Right-hand dominant 45 (84.9) Left-hand dominant 4 (7.5) Ambidextrous 3 (5.7) Level of training Junior Resident (R1-R3) 17 (32.1) Senior Resident (R4-R5) 12 (22.6) Fellow 16 (30.2) Staff Surgeon 8 (15.1) Specialty Urology 27 (50.9) ObGyn 13 (24.5) Thoracics 13 (24.5) Previous MIS experience (laparoscopic or thoracoscopic) None/minimal 17 (32.1) Moderate 11 (20.8) Significant 18 (34.0) Fellowship-trained in MIS 4 (7.5) Previous robotic surgery experience None 32 (60.4) Yes 21 (39.6) If yes, number of operative cases as surgical assistant 0 cases 33 (62.3) <10 cases 9 (17.0) 10-20 cases 3 (5.7) >20 cases 8 (9.4) If yes, number of operative cases at robotic console for at least 30 min 0 cases 41 (77.4) <10 cases 6 (11.3) 10-20 cases 1 (1.9) >20 cases 5 (9.4) MIS minimally invasive surgery Table 2 dVSS construct validity evidence dVSS exercise All subjects' overall score (%, mean +/- SD) Novice robotic surgeon overall score (%, mean +/- SD) Expert robotic surgeon overall score (%, mean +/- SD) p value Camera Targeting 1 69.943 +/- 21.7489 67.170 +/- 21.5258 91.667 +/- 4.2269 0.008 Peg Board 1 78.596 +/- 11.9824 76.913 +/- 11.6616 91.500 +/- 3.8341 0.004 Match Board 1 69.880 +/- 17.7691 67.864 +/- 17.9075 84.667 +/- 6.1860 0.028 Thread the Rings 74.152 +/- 16.4289 71.825 +/- 16.2605 89.667 +/- 5.8878 0.011 Suture Sponge 1 74.787 +/- 14.3086 73.171 +/- 14.5067 85.833 +/- 5.6716 0.042 Ring Walk 2 75.098 +/- 20.0861 73.333 +/- 20.1099 88.333 +/- 15.4100 0.086 Peg Board 2 84.308 +/- 11.7633 83.283 +/- 12.0861 92.167 +/- 3.6009 0.082 Table 3 dVSS concurrent validity evidence NP time NP errors RT time RT errors Camera Targeting 1 overall score 0.471 (0.001) 0.083 (0.575) 0.291 (0.045) 0.061 (0.685) Peg Board 1 overall score 0.486 (0.001) 0.141 (0.344) 0.325 (0.026) 0.088 (0.555) Match Board 1 overall score 0.543 (<0.001) 0.096 (0.530) 0.295 (0.050) 0.215 (0.162) Thread the Rings overall score 0.432 (0.005) 0.231 (0.147) 0.533 (<0.001) 0.163 (0.310) Suture Sponge 1 overall score 0.592 (<0.001) 0.105 (0.509) 0.437 (0.004) 0.015 (0.925) Ring Walk 2 overall score 0.454 (0.002) 0.179 (0.234) 0.399 (0.006) 0.022 (0.884) Peg Board 2 overall score 0.675 (<0.001) 0.058 (0.696) 0.073 (0.626) 0.045 (0.762) Subjects' overall score for each dVSS exercise is correlated with the time to complete (time) and number of errors (errors) for the Needle Passing (NP) and Ring Transfer (RT) tasks performed using the dVR. Data is expressed as Pearson correlation coefficient (p value). PMID- 27001877 TI - A pilot study of robotic uterine and vaginal vault manipulation: the ViKY Uterine PositionerTM. AB - A pilot study of uterine and vaginal vault manipulation using a new surgical robot-The ViKY Uterine PositionerTM--enrolled 36 cases comprising 31 hysterectomies, two myomectomies, two sacrocolpopexies and one excision of severe endometriosis performed between July 2010 and February 2012 in a tertiary referral District General Hospital in the UK. Mean age was 48 years, body mass index 25.7 kg/m(2) and uterine weight 231 g. Nine cases were foot-controlled and 27 by Bluetooth voice control. ViKY UPTM docking time once V-CareTM was inserted was 4.3 min. The device caused no peri-operative complications. Adequate mobilization, visualization and range of movement was possible in 81, 78 and 61 % of cases, respectively, with most of the problems arising in cases with uterine weight >350 g. ViKY UPTM was detached and an assistant was required in three cases, whilst V-CareTM came out of the uterus in one case. The learning curve led to various adjustments including optimizing patient position, increasing the device range of movement and adjusting device sensitivity. As a result, problems were minimized in our last nine cases. Adding robotic uterine manipulation is the obvious next step to give the gynecologist the ultimate control and stability of the uterus during robotic-assisted surgery without having to lift their head from the viewfinder or rely on a remotely situated perineal assistant. ViKY UPTM is the first device to deliver this. Pilot study results did not demonstrate compromised safety, and the device appears to be effective and easy to learn. PMID- 27001878 TI - Transoral robotic surgery and transoral laser microsurgery for oropharyngeal squamous cell cancer. AB - The aim of our study was to compare transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) for primary resection of oropharyngeal squamous cell cancer (OPSCC). This was a retrospective chart analysis of 33 patients with OPSCC treated at one academic medical center with either TORS (n = 17) or TLM (n = 16) between July 2008 and December 2010. Six patients in the TLM group and seven patients in the TORS group had primary cancer of the tonsil; the remaining patients had base of tongue cancer. Two patients in the TORS group had Stage I or II disease; the other 31 patients had Stage III [1/16 (6 %) TLM; 5/17 (29 %) TORS] or Stage IV cancer [15/16 (94 %) TLM; 10/17 (59 %) TORS]. The intervention was transoral surgery for OPSCC, and the main outcome measures were perioperative variables and functional outcomes. Mean operative time was 170 versus 115 min for TLM and TORS, respectively (p = 0.057). One patient, in the TLM group, required a temporary tracheostomy. Perioperative feeding tubes were placed in 6/16 (38 %) patients who underwent TLM and in 4/17 (24 %) patients who underwent TORS (p = 0.465). At a median follow-up of 14.5 months, the average MD Anderson Dysphagia Inventory score was 65.2 for TLM and 70.8 for TORS (p = 0.431). All TORS procedures were performed with a single oral retractor, while multiple laryngoscopes were required in 9/16 (56 %) TLM cases (p = 0.0003). The mean number of total specimens were 6.2 for TORS and 13.6 for TLM (p = 0.002). These results demonstrate that TLM and TORS have comparable perioperative variables with no significant differences in functional outcomes. For a subset of patients, TORS reduced the spatial complexity of surgery, suggested by the decreased need for multiple laryngoscopes, fewer specimens, and shorter operative times, while larger tumors were more amenable to TLM. PMID- 27001879 TI - Robotic adrenalectomy for a large right adrenal tumour. AB - The robotic approach for adrenalectomy has revolutionized the field of minimal access surgery for benign adrenal tumours. Robotic adrenal surgery has the edge over conventional laparoscopic adrenal surgery as it provides 3D stereoscopic vision, a high degree of dexterity with the use of EndoWrist instruments, and an ergonomic position for the surgeon. Here, we present our experience with robotic adrenal surgery in a large right adrenal tumour. PMID- 27001880 TI - Simultaneous robot-assisted radical cystoprostatectomy and nephroureterectomy in a patient with multifocal invasive urothelial carcinoma and previous contralateral nephroureterectomy. AB - We present a case of simultaneous robot-assisted radical cystoprostatectomy and nephroureterectomy with extended lymphadenectomy for multifocal invasive urothelial carcinoma in a patient with recurrent high-grade urothelial cancer and a previous right nephroureterectomy. The total urinary exenteration and extended lymphadenectomy was successfully performed with robot-assisted surgery in this unique case where the patient was rendered anephric at the end of the operation. We discuss the operative steps and the techniques performed to optimize the oncological results of robot-assisted surgery for invasive urothelial carcinoma, while attempting to preserve the renal function until the patient's urinary system was totally exenterated. PMID- 27001881 TI - Robot-assisted vaginal hysterectomy: two cases. AB - Hysterectomy remains the most frequent surgical gynaecological procedure. We report two cases of robot-assisted vaginal hysterectomy and show its feasibility. Robotic assistance in vaginal hysterectomy could combine both the advantage of the vaginal route (reducing surgical length, blood loss, hospitalisation and recovery), and the advantage of the robot assistance (3D endoscopic vision, easier instrumental handling, surgical ergonomics) especially when the hysterectomy is difficult. It could be used in other pathologies that are already treated by vaginal route. PMID- 27001882 TI - Robotic-assisted thoracoscopic resection of a benign anterior mediastinal teratoma. AB - There is an emerging body of evidence to support robotic-assisted mediastinal surgery, particularly for thymectomy. We describe the case of a 42-year-old woman with a benign anterior mediastinal teratoma resected by robotic-assisted thoracoscopy. This case illustrates the use of robotic-assisted surgery in a less commonly encountered mass of the anterior mediastinum. PMID- 27001883 TI - Prolonged steep Trendelenburg position: risk of postoperative upper airway obstruction. PMID- 27001884 TI - "The Lister Technique": a new technique for the management of the distal ureter during radical robotic nephroureterectomy. AB - We describe "The Lister Technique"-a new 3 step procedure developed in our department for robotic assisted laparoscopic nephroureterectomy (RANU). Our new technique facilitates the complete excision of the whole ureter including ureteric orifice and reduces this risk of tumour spillage from the distal ureter without the need for bivalving the bladder. Our initial data indicates that the technique is associated with reduction in bladder recurrence post-operatively in comparison to current published series. Longer follow up and larger patient numbers are required to validate these results further. PMID- 27001885 TI - Comparison of Macintosh, McCoy and C-MAC D-Blade video laryngoscope intubation by prehospital emergency health workers: a simulation study. AB - The aim of the this study is to evaluate the intubation success rates of emergency medical technicians using a Macintosh laryngoscope (ML), McCoy laryngoscope (MCL), and C MAC D-Blade (CMDB) video laryngoscope on manikin models with immobilized cervical spines. This randomized crossover study included 40 EMTs with at least 2 years' active service in ambulances. All participating technicians completed intubations in three scenarios-a normal airway model, a rigid cervical collar model, and a manual in-line cervical stabilization model with three different laryngoscopes. The scenario and laryngoscope model were determined randomly. We recorded the scenario, laryngoscope method, intubation time in seconds, tooth pressure, and intubation on a previously prepared study form. We performed Friedman tests to determine whether there is a significant change in the intubation success rate, duration of tracheal intubation, tooth pressure, and visual analog scale scores due to violations of parametric test assumptions. We performed the Wilcoxon test to determine the significance of pairwise differences for multiple comparisons. An overall 5 % type I error level was used to infer statistical significance. We considered a p value of less than 0.05 statistically significant. The CMDB and MCL success rates were significantly higher than the ML rates in all scenario models (p < 0.05). The CMDB intubation duration was significantly shorter when compared with ML and MCL in all models. CMDB and MCL may provide an easier, faster intubation by prehospital emergency health care workers in patients with immobilized cervical spines. PMID- 27001887 TI - Internal and Emergency Medicine from a 2016 perspective. PMID- 27001886 TI - Cardiovascular disease and hypertension in sub-Saharan Africa: burden, risk and interventions. AB - Cardiovascular disease, including stroke, heart failure and kidney disease, has been common in sub-Saharan Africa for many years, and rapid urbanization is causing an upsurge of ischaemic heart disease and metabolic disorders. At least two-thirds of cardiovascular deaths now occur in low- and middle-income countries, bringing a double burden of disease to poor and developing world economies. High blood pressure (or hypertension) is by far the commonest underlying risk factor for cardiovascular disease. Its prevention, detection, treatment and control in sub-Saharan Africa are haphazard and suboptimal. This is due to a combination of lack of resources and health-care systems, non-existent effective preventive strategies at a population level, lack of sustainable drug therapy, and barriers to complete compliance with prescribed medications. The economic impact for loss of productive years of life and the need to divert scarce resources to tertiary care are substantial. PMID- 27001888 TI - Renal denervation for resistant hypertension: no. AB - In recent years, catheter-based radiofrequency denervation of the renal arteries (RDN) has emerged as a potential treatment for resistant hypertension. Though initial non-randomized and randomized small studies demonstrate large reductions in office blood pressure, RDN superiority to conventional treatment is not confirmed either by randomized controlled trials or by large international registries. Increasing evidence supports the hypothesis that a rational pharmacological therapeutic scheme is equally or more effective; this approach, together with an intervention aimed at increasing patient's compliance with treatment, might solve most of the cases of refractory hypertension. Thus, based on current evidence, renal denervation should not be routinely used to treat resistant hypertension. Though the possibility that RDN might be useful in other subsets of hypertensive patients exists, it has never been proven. Thus, its use should be limited to extreme situations, when all other possible treatments have failed. PMID- 27001889 TI - Blood stains of the Turin Shroud 2015: beyond personal hopes and limitations of techniques. AB - In the early '80s, evidence was provided that, rather than a dye (red okra), hemoglobin was indeed responsible for the alleged blood stains of the Turin Shroud. Such stains were shown to belong to an MNS positive individual of the AB group, and the halos surrounding the blood stains were compatible with serum containing trace amounts of bilirubin, albumin and immunoglobulins. However, being only based on indirect and circumstantial evidence, most of these data were challenged. In the late '90s, together with the evidence of the gene coding beta globin, contamination between male and female DNA was documented on the Turin Shroud. Although the presence of male was more noticeable than female DNA, these data were considered null and void. These days, to establish that blood indisputably belongs to an MNS positive individual of the AB group, and to exclude DNA contamination, high-specificity techniques with monoclonal antibodies and molecular studies on nuclear and mitochondrial DNA are needed. Indeed, consistent with DNA contamination on the Turin Shroud, sequences from multiple subjects of different ethnic origins have been recently detected on the human mitochondrial genome extracted from dust particles of the linen. Innovative concepts are likely to come up using modern research approaches to evaluate the issue of blood stains of the Turin Shroud. Nor can we rule out the possibility that religious implications of the new findings on the Turin Shroud might be envisaged. Conceivably enough, the ongoing debate will be fierce and passionate, especially in the media. PMID- 27001891 TI - Thermally Activated Delayed Fluorescence Polymers for Efficient Solution Processed Organic Light-Emitting Diodes. AB - Thermally activated delayed fluorescence (TADF) pi-conjugated polymers are developed for solution-processed TADF-OLEDs. Benzophenone-based alternating donor acceptor structures contribute to the small ?EST , enabling efficient exciton harvesting through TADF. Solution-processed OLEDs using the TADF polymers as emitters can achieve high maximum external electroluminescence efficiencies of up to 9.3%. PMID- 27001890 TI - Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals. AB - Germline removal provokes longevity in several species and shifts resources towards survival and repair. Several Caenorhabditis elegans transcription factors regulate longevity arising from germline removal; yet, how they work together is unknown. Here we identify a Myc-like HLH transcription factor network comprised of Mondo/Max-like complex (MML-1/MXL-2) to be required for longevity induced by germline removal, as well as by reduced TOR, insulin/IGF signalling and mitochondrial function. Germline removal increases MML-1 nuclear accumulation and activity. Surprisingly, MML-1 regulates nuclear localization and activity of HLH 30/TFEB, a convergent regulator of autophagy, lysosome biogenesis and longevity, by downregulating TOR signalling via LARS-1/leucyl-transfer RNA synthase. HLH-30 also upregulates MML-1 upon germline removal. Mammalian MondoA/B and TFEB show similar mutual regulation. MML-1/MXL-2 and HLH-30 transcriptomes show both shared and preferential outputs including MDL-1/MAD-like HLH factor required for longevity. These studies reveal how an extensive interdependent HLH transcription factor network distributes responsibility and mutually enforces states geared towards reproduction or survival. PMID- 27001892 TI - Assessing the therapeutic efficacy of VEGFR-1-targeted polymer drug conjugates in mouse tumor models. AB - Polymer-drug conjugates that can actively target the tumor vasculature have emerged as an attractive technology for improving the therapeutic efficacy of cytotoxic drugs. We have recently provided, for the first time, in vivo evidence showing the significant advantage of the E-selectin-targeted N-(2 hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin conjugate, P-(Esbp) DOX, in inhibiting primary tumor growth and preventing the formation and development of cancer metastases. Here, we describe the design of a vascular endothelial growth factor receptor (VEGFR)-1-targeted HPMA copolymer-DOX conjugate (P-(F56)-DOX) that can actively and simultaneously target different cell types in the tumor microenvironment, such as endothelial cells (ECs), bone marrow-derived cells and many human cancer cells of diverse tumor origin. The VEGFR-1-targeted copolymer was tested for its binding, internalization and in vitro cytotoxicity in ECs (bEnd.3 and cEND cells) and cancer cells (B16-F10, 3LL and HT29). The in vivo anti-cancer activity of P-(F56)-DOX was then tested in two tumor-bearing mice (TBM) models (i.e., primary Lewis lung carcinoma (3LL) tumors and B16-F10 melanoma pulmonary metastases), relative to that of the E-selectin targeted system (P-(Esbp)-DOX) that solely targets ECs. Our results indicate that the binding and internalization profiles of the VEGFR-1-targeted copolymer were superior towards ECs as compared to cancer cells and correlated well to the level of VEGFR-1 expression in cells. Accordingly, the VEGFR-1-targeted copolymer (P (F56)-DOX) was more toxic towards bEnd.3 cells than to cancer cells, and exhibited significantly higher cytotoxicity than did the non-targeted control copolymer. P-(F56)-DOX inhibited 3LL tumor growth and significantly prolonged the survival of mice with B16-F10 pulmonary metastases. When compared to a system that actively targets only tumor vascular ECs, P-(F56)-DOX and P-(Esbp)-DOX exhibited comparable efficacy in slowing the growth of primary 3LL tumors and prolonging the survival of these mice. Still, P-(Esbp)-DOX had more pronounced anti-tumor activity in mice bearing B16-F10 lung metastases after a single intravenous injection, at an equivalent DOX dose. Overall, our results indicate that the VEGFR-1- and E-selectin-targeted drug delivery systems evaluated here show enhanced anti-cancer activity, and prolonged the survival of mice after a single intravenous injection. This is thus the first study comparing the anti tumor activity of VEGFR-1- and E-selectin-targeted polymer drug conjugates in the same TBM models at an equivalent drug dose. PMID- 27001895 TI - Unprecedented iron-catalyzed selective hydrogenation of activated amides to amines and alcohols. AB - The first example of hydrogenation of amides homogeneously catalyzed by an earth abundant metal complex is reported. The reaction is catalyzed by iron PNP pincer complexes. A wide range of secondary and tertiary N-substituted 2,2,2 trifluoroacetamides were hydrogenated to form amines and trifluoroethanol. PMID- 27001894 TI - A novel in situ hydrophobic ion paring (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system. AB - The present studies were aimed at formulating AZD2811-loaded polylactic acid polyethylene glycol (PLA-PEG) nanoparticles with adjustable release rates without altering the chemical structures of the polymer or active pharmaceutical ingredient (API). This was accomplished through the use of a hydrophobic ion pairing approach. A series of AZD2811-containing nanoparticles with a variety of hydrophobic counterions including oleic acid, 1-hydroxy-2-naphthoic acid, cholic acid, deoxycholic acid, dioctylsulfosuccinic acid, and pamoic acid is described. The hydrophobicity of AZD2811 was increased through formation of ion pairs with these hydrophobic counterions, producing nanoparticles with exceptionally high drug loading-up to five fold higher encapsulation efficiency and drug loading compared to nanoparticles made without hydrophobic ion pairs. Furthermore, the rate at which the drug was released from the nanoparticles could be controlled by employing counterions with various hydrophobicities and structures, resulting in release half-lives ranging from about 2 to 120h using the same polymer, nanoparticle size, and nanoemulsion process. Process recipe variables affecting drug load and release rate were identified, including pH and molarity of quench buffer. Ion pair formation between AZD2811 and pamoic acid as a model counterion was investigated using solubility enhancement as well as nuclear magnetic resonance spectroscopy to demonstrate solution-state interactions. Further evidence for an ion pairing mechanism of controlled release was provided through the measurement of API and counterion release profiles using high-performance liquid chromatography, which had stoichiometric relationships. Finally, Raman spectra of an AZD2811-pamoate salt compared well with those of the formulated nanoparticles, while single components (AZD2811, pamoic acid) alone did not. A library of AZD2811 batches was created for analytical and preclinical characterization. Dramatically improved preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development. PMID- 27001893 TI - Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma. AB - Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy. PMID- 27001896 TI - The development of Attitudes of People from Ethnic Minorities to Help-Seeking for Dementia (APEND): a questionnaire to measure attitudes to help-seeking for dementia in people from South Asian backgrounds in the UK. AB - BACKGROUND: People from South Asian backgrounds present to dementia services relatively late, often responding to crises. We aimed to devise and validate a theory of planned behaviour questionnaire to measure attitudes that predict medical help-seeking for UK-based South Asian people, to assess the effectiveness of future interventions promoting earlier help-seeking. METHODS: We used focus groups to establish the content validity of culturally relevant questionnaire items, then asked participants to complete the questionnaire. We analysed reliability and validity and established the concurrent validity of questionnaire attitudes through correlation with willingness to seek help from a doctor for memory problems. We also correlated the scale with knowledge of dementia. RESULTS: The strongest predictor of willingness to seek help was perceived social pressure from significant others around help-seeking; these attitudes were associated with beliefs about the views of family members and embarrassment around help-seeking. Willingness to seek help was also strongly associated with attitudes about the benefits of seeing a doctor for memory problems, attitudes that were related to specific beliefs about what doctors can do to help. Attitudes in the questionnaire predicted 77% of variance in willingness to seek help, but no relationship was found with dementia knowledge. CONCLUSIONS: We present the Attitudes of People from Ethnic Minorities to Help-Seeking for Dementia (APEND) questionnaire, a valid and reliable measure of attitudes that influence help-seeking for dementia in people from South Asian backgrounds, which could assess the impact of intervention studies. We suggest that interventions target attitudes specified here, rather than dementia knowledge. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001897 TI - Analysis of polymorphisms of genes associated with folate-mediated one-carbon metabolism and neural tube defects in Chinese Han Population. AB - BACKGROUND: The polymorphism of genes involved in folate-mediated one-carbon metabolism may be a risk factor for neural tube defects (NTDs). In the present study, we aimed to investigate the single nucleotide polymorphisms (SNPs) of the genes BHMT, CUBN, FTCD, GAMT, GART, SARDH, SHMT1, and MUT, and their effect on NTDs in the Chinese Han population. METHODS: A total of 270 NTDs cases and 192 controls were enrolled in this study. The SNPs were analyzed with the next generation sequencing method. The folate levels of brain tissues from 113 available NTDs cases and 123 available controls were measured. RESULTS: Next generation sequencing identified 818 single nucleotide variants, including 214 SNPs used for further analysis. Statistical analysis showed that two independent SNP loci, rs2797840 and rs2073817 in SARDH, may be associated with the susceptibility of NTDs. Specifically, the minor allele G of rs2797840 was significantly associated with NTDs risk in spina bifida subgroup (p value = 0.0348). For subjects whose folate content was measured, the protective allele G of rs2797840 was significantly associated with increased folate content of brain. rs2797840 is within several ENCODE regulatory regions, indicating this SNPs may influence expression of SARDH. CONCLUSION: The SNPs rs2797840 and rs2073817 in SARDH may serve as an indicator for the occurrence of NTDs in the Chinese Han population, and rs2797840 may also be an indicator for folate content of brain. PMID- 27001898 TI - Rare double spin canting antiferromagnetic behaviours in a [Co24] cluster. AB - A fish-basket-shaped [Co24] cluster, [Co24(MU3-O)4(ampc)4(MU3-OH)4(MU2 OH)4(NO3)5(HCO2)22(H2O)10].[(HCO2).2(CH3OH).x(H2O)], was woven by bridging oxygen atoms from O(2-), OH(-), NO3(-) and HCO2(-) groups, and stabilized terminally by a semi-rigid organic ligand 4',4'-[(dimethylamino)dimethylene]-bis[(1,1' biphenyl)-2-carboxylate] (ampc(-)). Magnetic analyses indicate that the [Co24] cluster exhibits two types of spin canting orders, spin flop and a small hysteresis with a coercive field of ca. 661 Oe and a remanent magnetization of 0.466 Nbeta. PMID- 27001900 TI - Surface-Plasmon-Enhanced Photodriven CO2 Reduction Catalyzed by Metal-Organic Framework-Derived Iron Nanoparticles Encapsulated by Ultrathin Carbon Layers. AB - Highly efficient utilization of solar light with an excellent reduction capacity is achieved for plasmonic Fe@C nanostructures. By carbon layer coating, the optimized catalyst exhibits enhanced selectivity and stability applied to the solar-driven reduction of CO2 into CO. The surface-plasmon effect of iron particles is proposed to excite CO2 molecules, and thereby facilitates the final reaction activity. PMID- 27001899 TI - Different states of synaptotagmin regulate evoked versus spontaneous release. AB - The tandem C2-domains of synaptotagmin 1 (syt) function as Ca(2+)-binding modules that trigger exocytosis; in the absence of Ca(2+), syt inhibits spontaneous release. Here, we used proline linkers to constrain and alter the relative orientation of these C2-domains. Short poly-proline helices have a period of three, so large changes in the relative disposition of the C2-domains result from changing the length of the poly-proline linker by a single residue. The length of the linker was varied one residue at a time, revealing a periodicity of three for the ability of the linker mutants to interact with anionic phospholipids and drive evoked synaptic transmission; syt efficiently drove exocytosis when its tandem C2-domains pointed in the same direction. Analysis of spontaneous release revealed a reciprocal relationship between the activation and clamping activities of the linker mutants. Hence, different structural states of syt underlie the control of distinct forms of synaptic transmission. PMID- 27001901 TI - Synthesis of highly substituted gamma-hydroxybutenolides through the annulation of keto acids with alkynes and subsequent hydroxyl transposition. AB - An efficient synthesis of highly functionalized gamma-hydroxybutenolides through BF3-catalyzed annulation of keto acids with alkynes is described. Many advantages such as the use of routine reagents, easy operation, and a 100% atom efficiency are demonstrated in the method. The reaction can be readily scaled up to gram quantities, offering good practicality. PMID- 27001902 TI - A new chapter in pharmaceutical manufacturing: 3D-printed drug products. AB - FDA recently approved a 3D-printed drug product in August 2015, which is indicative of a new chapter for pharmaceutical manufacturing. This review article summarizes progress with 3D printed drug products and discusses process development for solid oral dosage forms. 3D printing is a layer-by-layer process capable of producing 3D drug products from digital designs. Traditional pharmaceutical processes, such as tablet compression, have been used for decades with established regulatory pathways. These processes are well understood, but antiquated in terms of process capability and manufacturing flexibility. 3D printing, as a platform technology, has competitive advantages for complex products, personalized products, and products made on-demand. These advantages create opportunities for improving the safety, efficacy, and accessibility of medicines. Although 3D printing differs from traditional manufacturing processes for solid oral dosage forms, risk-based process development is feasible. This review highlights how product and process understanding can facilitate the development of a control strategy for different 3D printing methods. Overall, the authors believe that the recent approval of a 3D printed drug product will stimulate continual innovation in pharmaceutical manufacturing technology. FDA encourages the development of advanced manufacturing technologies, including 3D printing, using science- and risk-based approaches. PMID- 27001903 TI - Use of medications that antagonize mediators of inflammatory responses may reduce the risk of delirium in older adults: a nested case-control study. AB - OBJECTIVE: The objective of this study is to explore whether the use of medications that antagonize mediators of inflammatory responses reduces the risk of delirium in older adults. METHODS: A nested case-control study was conducted using data from a prospective study of delirium in older long-term care residents from 7 long-term care facilities in Montreal and Quebec City, Canada. The Confusion Assessment Method was used to diagnose incident delirium. The use of medications that antagonize mediators of inflammatory responses was determined by examining facility pharmacy databases and coding medications received daily by each resident. Risk sets were built using incidence density sampling: each risk set consisted of a case with incident delirium and all controls without incident delirium at the same date and facility. Conditional logistic regression was used to assess the association of exposure to inflammation antagonist medications with the incidence of delirium. RESULTS: Of 254 residents, 95 developed incident delirium during 24 weeks (cases); each case was matched with up to 35 controls. Unadjusted and adjusted odds ratios (95% CI) of delirium for residents exposed to at least one inflammation antagonist medication were 0.53 (0.34, 0.81) and 0.60 (0.38, 0.92), respectively. Estimates of the risk of incident delirium associated with specific medications and medication classes were mostly protective but not statistically significant. CONCLUSION: The use of medications that antagonize mediators of inflammatory responses may reduce the risk of delirium in older adults. Despite study limitations, the findings merit further investigation using larger patient samples, more precise measures of exposure and better control of potential confounding variables. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001904 TI - Maternal exposure to radiographic exams and major structural birth defects. AB - BACKGROUND: An increasing number of radiologic exams are performed in the United States, but very few studies have examined the effects of maternal exposure to radiologic exams during the periconceptional period and birth defects. OBJECTIVES: To assess the association between maternal exposure to radiologic exams during the periconceptional period and 19 categories of birth defects using a large population-based study of birth defects. METHODS: We studied 27,809 case mothers and 10,200 control mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. Maternal exposure to radiologic exams that delivered ionizing radiation to the urinary tract, lumbar spine, abdomen, or pelvis were identified based on the mother's report of type of radiologic exams, organ or body part scanned and the month during which the exam occurred RESULTS: Overall, 0.9% of mothers reported exposure to one of these types of radiographic exams during the periconceptional period. We observed significant associations between maternal exposure during the first trimester and isolated Dandy-Walker malformation (odds ratio = 7.7; 95% confidence interval, 1.8-33) and isolated d-transposition of the great arteries (odds ratio = 3.8; 95% confidence interval, 1.4-10.3). However, the result for isolated Dandy-Walker malformation was based on only two exposed cases. CONCLUSION: These results should be interpreted cautiously because multiple statistical tests were conducted and measurements of exposure were based on maternal report. However, our results may be useful for generating hypotheses for future studies. Birth Defects Research (Part A) 106:563-572, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27001905 TI - Super-resolution imaging-based single particle tracking reveals dynamics of nanoparticle internalization by live cells. AB - By combining super-resolution photoactivation localization microscopy with single particle tracking, we have visualized the endocytic process in the live-cell environment with nanoparticles (NPs) of different size and surface functionalization. This allowed us to analyze the dynamics of NPs interacting with cells with high spatial and temporal resolution. We identified two distinctly different types of pathways by which NPs are internalized via clathrin coated pits (CCPs). Predominantly, NPs first bind to the membrane and, subsequently, CCPs form at this site. However, there are also instances where a NP diffuses on the membrane and utilizes a preformed CCP. Moreover, we have applied this new method to further explore the effects of size and surface functionalization on the NP dynamics on the plasma membrane and the ensuing endocytosis. PMID- 27001908 TI - Cationic aluminum hydride complexes: reactions of carbene-alane adducts with trityl-borate. AB - Reaction of (Idipp)AlH3 with [Ph3C][B(C6F5)4] in toluene affords the dimeric aluminum dication [((Idipp)AlH(MU-H))2][B(C6F5)4]22. In contrast, the reaction of (IBn)AlH3 with [Ph3C][B(C6F5)4] in bromobenzene gives a redistribution product, the salt of a monomeric dication [(IBn)2AlH][B(C6F5)4]24. PMID- 27001906 TI - MicroRNA-378 limits activation of hepatic stellate cells and liver fibrosis by suppressing Gli3 expression. AB - Hedgehog (Hh) signalling regulates hepatic fibrogenesis. MicroRNAs (miRNAs) mediate various cellular processes; however, their role in liver fibrosis is unclear. Here we investigate regulation of miRNAs in chronically damaged fibrotic liver. MiRNA profiling shows that expression of miR-378 family members (miR-378a 3p, miR-378b and miR-378d) declines in carbon tetrachloride (CCl4)-treated compared with corn-oil-treated mice. Overexpression of miR-378a-3p, directly targeting Gli3 in activated hepatic stellate cells (HSCs), reduces expression of Gli3 and profibrotic genes but induces gfap, the inactivation marker of HSCs, in CCl4-treated liver. Smo blocks transcriptional expression of miR-378a-3p by activating the p65 subunit of nuclear factor-kappaB (NF-kappaB). The hepatic level of miR-378a-3p is inversely correlated with the expression of Gli3 in tumour and non-tumour tissues in human hepatocellular carcinoma. Our results demonstrate that miR-378a-3p suppresses activation of HSCs by targeting Gli3 and its expression is regulated by Smo-dependent NF-kappaB signalling, suggesting miR 378a-3p has therapeutic potential for liver fibrosis. PMID- 27001907 TI - Sleep disturbances are key symptoms of very early stage Alzheimer disease with behavioral and psychological symptoms: a Japan multi-center cross-sectional study (J-BIRD). AB - BACKGROUND: Sleep disturbances in Alzheimer disease (AD) may affect behavioral and psychological symptoms of dementia (BPSD). Our aim was to elucidate the associations between sleep disturbances and other BPSD at different stages of AD. METHODS: This investigation was part of a multicenter-retrospective study in Japan (J-BIRD). Eligible for final analyses were 684 AD patients. Global severity of dementia was estimated using the Clinical Dementia Rating (CDR) scale. BPSD were assessed using the Neuropsychiatric Inventory (NPI). We analyzed the relationships between sleep disturbances and BPSD at different stages of AD according to the CDR score. RESULTS: Among the 684 AD patients, 146 (21.3%) had sleep disturbances. Patients with very early AD (CDR 0.5) and sleep disturbances had significantly more BPSD than those without sleep disturbances, as indicated by the higher prevalence of the following four NPI items: anxiety, euphoria, disinhibition, and aberrant motor behavior. In AD at CDR 2, (moderate AD) only one NPI item (irritability) was affected, while none was affected at CDR 1 (mild AD) and 3 (severe AD). Multiple regression analyses were performed in those with AD having various CDR scores. At CDR 0.5, the presence of sleep disturbances was associated with a high total NPI score (beta = 0.32, p < 0.001). However, other factors, including cognitive decline, age, gender, and years of education, were not significantly associated with the NPI score. At CDR 1 and 2, no factor was significantly related to BPSD. CONCLUSION: Sleep disturbances were strongly associated with other BPSD in the very early stage of AD. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27001909 TI - Precision medicine company takes aim at genetically based epilepsy: Pairnomix offers individualized genetic research services. PMID- 27001910 TI - Spectrum of gene variants linked to cystic fibrosis in nonwhites: Research finds certain screening panels may be inadequate. PMID- 27001914 TI - Synthesis of novel polycyano-containing organic ligands via double carbanion cleavage of 1',3'-dioxo-1',3'-dihydrospiro[cyclopropane-1,2'-indene] derivatives. AB - A novel fast, convenient and inexpensive synthesis of 1',3'-dioxo-1',3' dihydrospiro[cyclopropane-1,2'-indene]-2,2,3,3-tetracarbonitrile and dimethyl 2,3 dicyano-1',3'-dioxo-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-2,3 dicarboxylate is reported. These compounds undergo double carbanion cleavage under the action of alcohols resulting in the formation of stable salts, containing new allylic-type anions with potential application in organic electronics and as ionic liquid components. PMID- 27001912 TI - Extending the mutation spectrum for Galloway-Mowat syndrome to include homozygous missense mutations in the WDR73 gene. AB - Galloway-Mowat syndrome is a rare autosomal-recessive disorder classically described as the combination of microcephaly and nephrotic syndrome. Recently, homozygous truncating mutations in WDR73 (WD repeat domain 73) were described in two of 31 unrelated families with Galloway-Mowat syndrome which was followed by a report of two sibs in an Egyptian consanguineous family. In this report, seven affecteds from four families showing biallelic missense mutations in WDR73 were identified by exome sequencing and confirmed to follow a recessive model of inheritance. Three-dimensional modeling predicted conformational alterations as a result of the mutation, supporting pathogenicity. An additional 13 families with microcephaly and renal phenotype were negative for WDR73 mutations. Missense mutations in the WDR73 gene are reported for the first time in Galloway-Mowat syndrome. A detailed phenotypic comparison of all reported WDR73-linked Galloway Mowat syndrome patients with WDR73 negative patients showed that WDR73 mutations are limited to those with classical Galloway-Mowat syndrome features, in addition to cerebellar atrophy, thin corpus callosum, brain stem hypoplasia, occasional coarse face, late-onset and mostly slow progressive nephrotic syndrome, and frequent epilepsy. PMID- 27001915 TI - Calcium-based multi-element chemistry for grid-scale electrochemical energy storage. AB - Calcium is an attractive material for the negative electrode in a rechargeable battery due to its low electronegativity (high cell voltage), double valence, earth abundance and low cost; however, the use of calcium has historically eluded researchers due to its high melting temperature, high reactivity and unfavorably high solubility in molten salts. Here we demonstrate a long-cycle-life calcium metal-based rechargeable battery for grid-scale energy storage. By deploying a multi-cation binary electrolyte in concert with an alloyed negative electrode, calcium solubility in the electrolyte is suppressed and operating temperature is reduced. These chemical mitigation strategies also engage another element in energy storage reactions resulting in a multi-element battery. These initial results demonstrate how the synergistic effects of deploying multiple chemical mitigation strategies coupled with the relaxation of the requirement of a single itinerant ion can unlock calcium-based chemistries and produce a battery with enhanced performance. PMID- 27001918 TI - Fe-catalyzed synthesis of substituted N-aryl oxazolidines. AB - A novel iron-catalyzed synthesis of substituted N-aryl oxazolidines was developed via C-N bond formation and methylenation. The reaction of aryl hydroxylamines with allyl alcohols, in the presence of formaldehyde or its equivalents, afforded variety of oxazolidine heterocycles in very good yields. This catalytic method is most effective for para-substituted aryl hydroxylamines and 3-methyl allyl alcohols. Furthermore, acid catalyzed demethylenation of oxazolidines allowed access to N-aryl amino alcohols in good yields. PMID- 27001916 TI - Copper-catalyzed regio- and enantioselective aminoboration of alkylidenecyclopropanes: the synthesis of cyclopropane-containing beta aminoalkylboranes. AB - A Cu-catalyzed regio- and enantioselective aminoboration of alkylidenecyclopropanes (ACPs) with bis(pinacolato)-diboron (B2pin2) and hydroxylamines has been described in this paper, affording the corresponding cyclopropane-containing beta-aminoalkylboranes in good yields under mild conditions. Moreover, a catalytic asymmetric variant of this transformation has also been realized by using a copper complex with a (S)-BINAP ligand along with further transformation of the product to give cyclopropane-containing 1,2 aminoalcohols. PMID- 27001919 TI - Synergistic eradication of antibiotic-resistant bacteria based biofilms in vivo using a NIR-sensitive nanoplatform. AB - In this work, a novel multifunctional NIR-sensitive nanoplatform has been developed for synergistic eradication of antibiotic-resistant bacteria based biofilms in vitro and in vivo. With high biocompatibility and an outstanding synergistic effect, our system provides a promising avenue to preventing and combating biofilm-associated infections. PMID- 27001920 TI - Regulation of mitochondrial calcium in plants versus animals. AB - Ca(2+) acts as an important cellular second messenger in eukaryotes. In both plants and animals, a wide variety of environmental and developmental stimuli trigger Ca(2+) transients of a specific signature that can modulate gene expression and metabolism. In animals, mitochondrial energy metabolism has long been considered a hotspot of Ca(2+) regulation, with a range of pathophysiology linked to altered Ca(2+) control. Recently, several molecular players involved in mitochondrial Ca(2+) signalling have been identified, including those of the mitochondrial Ca(2+) uniporter. Despite strong evidence for sophisticated Ca(2+) regulation in plant mitochondria, the picture has remained much less clear. This is currently changing aided by live imaging and genetic approaches which allow dissection of subcellular Ca(2+) dynamics and identification of the proteins involved. We provide an update on our current understanding in the regulation of mitochondrial Ca(2+) and signalling by comparing work in plants and animals. The significance of mitochondrial Ca(2+) control is discussed in the light of the specific metabolic and energetic needs of plant and animal cells. PMID- 27001921 TI - High resolution mapping of traits related to whole-plant transpiration under increasing evaporative demand in wheat. AB - Atmospheric vapor pressure deficit (VPD) is a key component of drought and has a strong influence on yields. Whole-plant transpiration rate (TR) response to increasing VPD has been linked to drought tolerance in wheat, but because of its challenging phenotyping, its genetic basis remains unexplored. Further, the genetic control of other key traits linked to daytime TR such as leaf area, stomata densities and - more recently - nocturnal transpiration remains unknown. Considering the presence of wheat phenology genes that can interfere with drought tolerance, the aim of this investigation was to identify at an enhanced resolution the genetic basis of the above traits while investigating the effects of phenology genes Ppd-D1 and Ppd-B1 Virtually all traits were highly heritable (heritabilities from 0.61 to 0.91) and a total of mostly trait-specific 68 QTL were detected. Six QTL were identified for TR response to VPD, with one QTL (QSLP.ucl-5A) individually explaining 25.4% of the genetic variance. This QTL harbored several genes previously reported to be involved in ABA signaling, interaction with DREB2A and root hydraulics. Surprisingly, nocturnal TR and stomata densities on both leaf sides were characterized by highly specific and robust QTL. In addition, negative correlations were found between TR and leaf area suggesting trade-offs between these traits. Further, Ppd-D1 had strong but opposite effects on these traits, suggesting an involvement in this trade-off. Overall, these findings revealed novel genetic resources while suggesting a more direct role of phenology genes in enhancing wheat drought tolerance. PMID- 27001923 TI - Facile creation of FRET systems from a pH-responsive AIE fluorescent vesicle. AB - We demonstrate a facile approach to constructing aggregation induced emission (AIE) fluorescent vesicles assembled using a PEG-POSS-(TPE)7 polymer. The narrow wall thickness provides an ideal confined space for creating fluorescence resonance energy transfer (FRET) systems between TPE donors and encapsulated FITC or DOX acceptors. PMID- 27001922 TI - Nucleation of amorphous shear bands at nanotwins in boron suboxide. AB - The roles of grain boundaries and twin boundaries in mechanical properties are well understood for metals and alloys. However, for covalent solids, their roles in deformation response to applied stress are not established. Here we characterize the nanotwins in boron suboxide (B6O) with twin boundaries along the {0111} planes using both scanning transmission electron microscopy and quantum mechanics. Then, we use quantum mechanics to determine the deformation mechanism for perfect and twinned B6O crystals for both pure shear and biaxial shear deformations. Quantum mechanics suggests that amorphous bands nucleate preferentially at the twin boundaries in B6O because the twinned structure has a lower maximum shear strength by 7.5% compared with perfect structure. These results, which are supported by experimental observations of the coordinated existence of nanotwins and amorphous shear bands in B6O, provide a plausible atomistic explanation for the influence of nanotwins on the deformation behaviour of superhard ceramics. PMID- 27001924 TI - The synthesis of a series of adenosine A3 receptor agonists. AB - A series of 1'-(6-aminopurin-9-yl)-1'-deoxy-N-methyl-beta-d-ribofuranuronamides that were characterised by 2-dialkylamino-7-methyloxazolo[4,5-b]pyridin-5 ylmethyl substituents on N6 of interest for screening as selective adenosine A3 receptor agonists, have been synthesised. This work involved the synthesis of 2 dialkylamino-5-aminomethyl-7-methyloxazolo[4,5-b]pyridines and analogues that were coupled with the known 1'-(6-chloropurin-9-yl)-1'-deoxy-N-methyl-beta-d ribofuranuronamide. The oxazolo[4,5-b]pyridines were synthesized by regioselective functionalisation of 2,4-dimethylpyridine N-oxides. The regioselectivities of these reactions were found to depend upon the nature of the heterocycle with 2-dimethylamino-5,7-dimethyloxazolo[4,5-b]pyridine-N-oxide undergoing regioselective functionalisation at the 7-methyl group on reaction with trifluoroacetic anhydride in contrast to the reaction of 4,6-dimethyl-3 hydroxypyridine-N-oxide with acetic anhydride that resulted in functionalisation of the 6-methyl group. To optimise selectivity for the A3 receptor, 5-aminomethyl 7-bromo-2-dimethylamino-4-[(3-methylisoxazol-5-yl)methoxy]benzo[d]oxazole was synthesised and coupled with the 1'-(6-chloropurin-9-yl)-1'-deoxy-N-methyl-beta-d ribofuranuronamide. The products were active as selective adenosine A3 agonists. PMID- 27001925 TI - Growth, nutritional, and gastrointestinal aspects of focal dermal hypoplasia (Goltz-Gorlin syndrome). AB - Focal dermal hypoplasia (FDH) is a rare genetic disorder caused by mutations in the PORCN gene located on the X-chromosome. In the present study, we characterized the pattern of growth, body composition, and the nutritional and gastrointestinal aspects of children and adults (n = 19) affected with this disorder using clinical anthropometry and a survey questionnaire. The mean birth length (P < 0.06) and weight (P < 0.001) z-scores of the participants were lower than the reference population. The mean head circumference (P < 0.001), height (length) (P < 0.001), weight (P < 0.01), and BMI (P < 0.05) for age z-scores of the participants were lower than the reference population. The height-for-age and weight-for-age z-scores of the participants did not differ significantly between birth and current measurements. Three-fourths of the group reported having one or more nutritional or gastrointestinal problems including short stature (65%), underweight (77%), oral motor dysfunction (41%), gastroesophageal reflux (24%), gastroparesis (35%), and constipation (35%). These observations provide novel clinical information about growth, body composition, and nutritional and gastrointestinal aspects of children and adults with FDH and underscore the importance of careful observation and early clinical intervention in the care of individuals affected with this disorder. PMID- 27001926 TI - Ophthalmologic manifestations of focal dermal hypoplasia (Goltz syndrome): A case series of 18 patients. AB - Focal Dermal Hypoplasia (FDH) or Goltz syndrome is a rare multi-system disorder with cutaneous, ocular, dental, and skeletal anomalies due to dysplasia of mesoectodermal derived tissues. It is an X-linked inheritance syndrome caused by mutations in the PORCN gene. This study is aimed to investigate the ocular findings in patients with Goltz syndrome. To date, there have been a limited number of case reports on the ocular manifestations of FDH. This is a prospective, non-consecutive, observational case series. Prospective ophthalmologic evaluation was performed on 18 patients with confirmed genetic testing for FDH, Goltz Syndrome, as a component of a larger multi-subspecialty study to better characterize the findings of this condition. Special attention was placed on evaluating the incidence of anophthalmia, microphthalmia, colobomas (iris, optic nerve, and/or retinal), cataracts, nystagmus, and strabismus. A complete ophthalmologic exam was done on all the patients. The mean patient age was 12.8 years (1-55 years). Eighty-nine percent were female and 77% (14/18) of patients had some form of an ophthalmologic manifestation of the condition. Ophthalmological findings included chorioretinal colobomas (61%), iris colobomas (50%), microphthalmia (44%), anophthalmia (11%), cataracts (11%), and conjunctival and eyelid papillomas (5%). Nystagmus was present in 33% and strabismus in 22% of the patients. Visual acuity ranged from 20/20 to no light perception. This study demonstrates a higher incidence of ophthalmologic manifestations as previously reported (77% vs. 40%). To our knowledge, this is the largest case series reported in the literature with 18 patients. PMID- 27001927 TI - Gynecologic findings in Goltz syndrome: A case series. AB - There is limited information available related to the gynecologic findings in Goltz syndrome. We report exclusively on external genitalia findings in 17 girls with a known diagnosis of focal dermal hypoplasia. This is the largest series to date. Some of our findings have been reported previously; however, some novel features including short perineum body not previously mentioned are noted as well. We recommend referral to a pediatric gynecologist for early evaluation of the reproductive tract as this can have an impact on the future fertility of these girls. PMID- 27001929 TI - Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation. AB - Although proteins mediate highly ordered DNA organization in vivo, theoretical studies suggest that homologous DNA duplexes can preferentially associate with one another even in the absence of proteins. Here we combine molecular dynamics simulations with single-molecule fluorescence resonance energy transfer experiments to examine the interactions between duplex DNA in the presence of spermine, a biological polycation. We find that AT-rich DNA duplexes associate more strongly than GC-rich duplexes, regardless of the sequence homology. Methyl groups of thymine acts as a steric block, relocating spermine from major grooves to interhelical regions, thereby increasing DNA-DNA attraction. Indeed, methylation of cytosines makes attraction between GC-rich DNA as strong as that between AT-rich DNA. Recent genome-wide chromosome organization studies showed that remote contact frequencies are higher for AT-rich and methylated DNA, suggesting that direct DNA-DNA interactions that we report here may play a role in the chromosome organization and gene regulation. PMID- 27001930 TI - Transition-metal-free cascade reaction of alpha-halo-N-tosylhydrazones, indoles and arylboronic acids. AB - alpha-Halo-N-tosylhydrazones are employed as reagents for the formation of multiple carbon-carbon bonds in the three-component reactions. In this transformation, a strategy has been designed to generate the diazo intermediate by using a nucleophile to react with the azoalkene intermediate generated in situ from the alpha-halo-N-tosylhydrazone. The diazo intermediate thus generated further undergoes transition-metal-free C-C bond forming reaction with arylboronic acids. PMID- 27001931 TI - Flow-dependent separation selectivity for organic molecules on metal-organic frameworks containing adsorbents. AB - A new flow-dependent separation selectivity (FDSS) effect was discovered in isocratic HPLC. Significant changes in chromatographic selectivity were achieved by simple variation of the mobile phase flow rate. The FDSS effect was observed for a core-shell stationary phase using silica particles as a core and a Zr-based metal-organic framework (UiO-66) as a shell. PMID- 27001932 TI - Crowned spiropyran fluoroionophores with a carboxyl moiety for the selective detection of lithium ions. AB - The absorbance and fluorescence spectra of carboxylated spiropyrans containing methyl-1-aza-12-crown-4, methyl-1-aza-15-crown-5, methyl-1-aza-18-crown-6 moieties are compared. Characteristic changes in spectra after addition of the alkali metal salts of Li(+), Na(+), K(+) and Cs(+) were observed. Chromism induced by the binding of the metal cations was observed as an increase in absorbance and fluorescence. Of these metal cations, the Li(+) ion produced the largest change in all three spiropyran systems. Reversible photoswitching of the spiropyran-metal complexes was observed on irradiation with alternating 352 nm UV and white light. This results in reversible fluorescence based sensing of lithium ions with potential for use in a biological sensor device. PMID- 27001933 TI - Stabilization of pre-optimized multicolor antibody cocktails for flow cytometry applications. AB - BACKGROUND: Flow cytometry has a multitude of applications in nearly all fields of biology. Newly described biological markers enable the creation of novel reagents which then aid in the elucidation of unique subsets of cells and their potential role in health and disease. In order to enable the simultaneous detection of an even greater number of parameters, the future progress of flow cytometry relies on advances in instrument engineering and the parallel development of new fluorophores. METHODS: In order to address the issues of reagent reliability, reproducibility, and work-flow optimization, we have used the freeze-dry technique to stabilize pre-mixed, pre-optimized, multicolor 'cocktails' of antibodies within 12 * 75 mm flow cytometry tubes (Lyotube). In this study we describe several lyophilized stabilized reagent combinations that are functional for extended periods of time (18 months and beyond), and can be stored at ambient temperature, eliminating cold-chain requirements during transportation and storage. This improves precision and reduces the redundant labor and error-potential associated with mixing antibodies to create "home-brew" cocktails. RESULTS: We have stained different types of samples including normal and leukemic whole blood, bone marrow, and PBMCs, as well as cell lines, directly with BD Lyotube reagents: The data show comparable and consistent performance of multiple batches of dehydrated, stabilized mixtures of antibodies and their liquid counterparts. CONCLUSIONS: The approach we describe here, the Lyotube, facilitates the improvement and implementation of standardization measures in clinical settings and in multi-site studies, a useful tool which can also be applied to determining the efficacy and safety of candidate therapeutics and vaccines. (c) 2016 International Clinical Cytometry Society. PMID- 27001934 TI - Boosting the photocatalytic performance of (001) BiOI: enhancing donor density and separation efficiency of photogenerated electrons and holes. AB - Herein, we demonstrate a simple strategy to boost the photocatalytic performance of BiOI by introducing oxygen defects into the BiOI. The oxygen-deficient BiOI exhibits superior photocatalytic performance for the degradation of formaldehyde gas. The enhancement of photocatalytic activity is due to the enhanced separation and migration efficiency of photogenerated electrons and holes. PMID- 27001935 TI - Discovery of abnormal lithium-storage sites in molybdenum dioxide electrodes. AB - Developing electrode materials with high-energy densities is important for the development of lithium-ion batteries. Here, we demonstrate a mesoporous molybdenum dioxide material with abnormal lithium-storage sites, which exhibits a discharge capacity of 1,814 mAh g(-1) for the first cycle, more than twice its theoretical value, and maintains its initial capacity after 50 cycles. Contrary to previous reports, we find that a mechanism for the high and reversible lithium storage capacity of the mesoporous molybdenum dioxide electrode is not based on a conversion reaction. Insight into the electrochemical results, obtained by in situ X-ray absorption, scanning transmission electron microscopy analysis combined with electron energy loss spectroscopy and computational modelling indicates that the nanoscale pore engineering of this transition metal oxide enables an unexpected electrochemical mass storage reaction mechanism, and may provide a strategy for the design of cation storage materials for battery systems. PMID- 27001937 TI - Dynamic covalent assembly and disassembly of nanoparticle aggregates. AB - The quantitative assembly and disassembly of a new type of dynamic covalent nanoparticle (NP) building block is reported. In situ spectroscopic characterization reveals constitutionally adaptive NP-bound monolayers of boronate esters. Ditopic linker molecules are used to produce covalently connected AuNP assemblies, displaying open dendritic morphologies, and which, despite being linked by covalent bonds, can be fully disassembled on application of an appropriate chemical stimulus. PMID- 27001936 TI - The Three Domains of Conservation Genetics: Case Histories from Hawaiian Waters. AB - The scientific field of conservation biology is dominated by 3 specialties: phylogenetics, ecology, and evolution. Under this triad, phylogenetics is oriented towards the past history of biodiversity, conserving the divergent branches in the tree of life. The ecological component is rooted in the present, maintaining the contemporary life support systems for biodiversity. Evolutionary conservation (as defined here) is concerned with preserving the raw materials for generating future biodiversity. All 3 domains can be documented with genetic case histories in the waters of the Hawaiian Archipelago, an isolated chain of volcanic islands with 2 types of biodiversity: colonists, and new species that arose from colonists. This review demonstrates that 1) phylogenetic studies have identified previously unknown branches in the tree of life that are endemic to Hawaiian waters; 2) population genetic surveys define isolated marine ecosystems as management units, and 3) phylogeographic analyses illustrate the pathways of colonization that can enhance future biodiversity. Conventional molecular markers have advanced all 3 domains in conservation biology over the last 3 decades, and recent advances in genomics are especially valuable for understanding the foundations of future evolutionary diversity. PMID- 27001938 TI - [Development and basics of metabolic monitoring in dairy cows. Focus on research in Eastern Germany and at the University of Leipzig, Germany]. AB - Systematic metabolic monitoring began in German-speaking countries in the late 1960s, early 1970s, due to an increase in metabolic disorders as a cause of infertility and mastitis and aimed at their prevention through early diagnosis. Development of a unified monitoring standard: Initiated by Rossow, Gurtler, Ehrentraut, Seidel and Furcht a standard "metabolic monitoring in cattle production" was developed in the 1970s. It included farm analysis, clinical and biochemical controls, prophylaxis and follow-up controls. Key points were: periodic screenings of heavily loaded, healthy indicator animals 2-4 days post partum (p. p.), 2-8 weeks p. p. and 1-2 weeks ante partum, maximal 10 animals/group, pooled samples are useful, optimal are individual samples, use of informative sample substrate and parameters, precise handling of specimens, expert assessment and follow-up. Metabolic controls during 1982-1989 in approximately 242 000 cows revealed means of 32.9% ketoses, 20.0% metabolic acidosis, 21.9% metabolic alkalosis, 34.2% nitrogen-metabolism disorders, 17.3% sodium deficiency and 23.7% liver disorders. Development of a metabolic profile after 1989: Reference values at higher milk yield, early diagnosis of diseases of the fat mobilization syndrome and improved early diagnosis by new indicators, including creatine kinase (CK), alkaline phosphatase (AP) with isoenzymes, acute phase proteins, cytokines, antioxidants, carnitine and lipoprotein fractions, were established. Optimized blood and urine screenings have important advantages over milk analysis. They are an important method of health and performance stabilization by exact analysis of causes and derived prevention. CLINICAL RELEVANCE: The fertility related parameters free fatty acids, beta hydroxybutyrate, urea, inorganic phosphate, CK, AP, sodium, potassium, selenium, copper, beta-carotene and net acid-base excretion proved to be a standard spectrum for screenings. These should be tested once a year/herd, if necessary as an inexpensive pool sample for approximately 50 ?. PMID- 27001939 TI - Expression of death receptor 3 on peripheral blood mononuclear cells differes in adult IBD patients and children with newly diagnosed IBD. AB - BACKGROUND: Interaction between TL1A and death receptor 3 (DR3) is associated with the pathogenesis of inflammatory bowel disease (IBD), although their role in the development of this disease remains not fully explained. Some studies showed elevated expression of TL1A and DR3 in inflamed intestinal tissue but currently there are no reports concerning expression of DR3 on peripheral blood mononuclear cells (PBMCs) of IBD patients which was the subject of our study. METHODS: We performed flow cytometry analysis of DR3 expression on CD4(+), CD8(+), CD11c(+), CD14(+) or CD20(+) PBMCs of adults and children with IBD and healthy volunteers with respect to C-reactive protein (CRP) levels in blood. Blood samples were collected from pediatric patients before the beginning of therapy, whereas adults patients were undergoing anti-inflammatory IBD treatment and had much lower CRP levels. RESULTS: With regard to appropriate healthy volunteers, children with IBD had elevated percentage of DR3-expressing CD4(+), CD8(+), CD11c(+) and CD20(+) PBMCs which, with the exception of DR3(+) CD11c(+) cells in children with ulcerative colitis, was correlated with CRP level in blood. Adult patients had increased frequency of DR3(+) CD8(+) and CD20(+) PBMCs and their CRP levels correlated only with DR3(+) CD8(+) cells. CONCLUSIONS: In comparison to healthy volunteers, untreated children with IBD have higher percentage of DR3(+) PBMCs than adults with IBD undergoing anti-inflammatory treatment. In most of the investigated PBMCs populations, the frequency of DR3(+) cells is correlated with the level of CRP. We suggest anti-inflammatory treatment may lead to reduction in the frequency of DR3(+) PBMCs. (c) 2016 International Clinical Cytometry Society. PMID- 27001942 TI - 1,1-Disubstituted olefin synthesis via Ni-catalyzed Markovnikov hydroalkylation of alkynes with alkyl halides. AB - A Ni-catalyzed Markovnikov hydroalkylation of alkynes with alkyl halides is described. The reaction proceeds smoothly without the use of sensitive organometallic reagents and shows good functional-group compatibility, enabling the efficient synthesis of a variety of 1,1-disubstituted olefins. It also provides a straightforward approach for the modification of complex organic molecules. PMID- 27001940 TI - Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration. AB - Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL 1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL 1beta which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3beta/beta-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications. PMID- 27001941 TI - An evaluation of the engraftment and the blood flow of porcine skin autografts inactivated by high hydrostatic pressure. AB - We previously reported that exposure to a high hydrostatic pressure (HHP) of 200 MPa could completely inactivate porcine skin without damaging the extracellular matrix. In this study, we used an autologous porcine skin graft model and explored whether the skin inactivated by HHP could be engrafted without inflammation to the residual cellular components. Twenty-one full-thickness skin grafts of 1.5 * 1.5 cm in size were prepared from a minipig (n = 2). Grafts were either nonpressurized or pressurized to 100, 150, 200, 300, 500, or 1000 MPa (n = 3) and randomly implanted on the fascia and removed at 1 and 4 weeks after grafting. All grafts showed complete engraftment at the macroscopic level and microcirculation was detected by a full-field laser speckle perfusion imager. The epidermis was removed and skin appendages were not observed in the grafts pressurized to more than 200 MPa. Azan and Elastica van Gieson staining showed no sign of dermal collagen fiber degeneration, while elastin fibers were observed. The fibroblasts and capillaries were observed to have infiltrated to dermis in all groups without severe inflammation. In conclusion, we showed that skin inactivated by HHP up to 1000 MPa could be engrafted successfully without removing cellular remnants. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1091-1101, 2017. PMID- 27001943 TI - Microchannel neural interface manufacture by stacking silicone and metal foil laminae. AB - OBJECTIVE: Microchannel neural interfaces (MNIs) overcome problems with recording from peripheral nerves by amplifying signals independent of node of Ranvier position. Selective recording and stimulation using an MNI requires good insulation between microchannels and a high electrode density. We propose that stacking microchannel laminae will improve selectivity over single layer MNI designs due to the increase in electrode number and an improvement in microchannel sealing. APPROACH: This paper describes a manufacturing method for creating MNIs which overcomes limitations on electrode connectivity and microchannel sealing. Laser cut silicone-metal foil laminae were stacked using plasma bonding to create an array of microchannels containing tripolar electrodes. Electrodes were DC etched and electrode impedance and cyclic voltammetry were tested. MAIN RESULTS: MNIs with 100 MUm and 200 MUm diameter microchannels were manufactured. High electrode density MNIs are achievable with electrodes present in every microchannel. Electrode impedances of 27.2 +/- 19.8 kOmega at 1 kHz were achieved. Following two months of implantation in Lewis rat sciatic nerve, micro-fascicles were observed regenerating through the MNI microchannels. SIGNIFICANCE: Selective MNIs with the peripheral nervous system may allow upper limb amputees to control prostheses intuitively. PMID- 27001944 TI - Serum ST2 in inflammatory bowel disease: a potential biomarker for disease activity. AB - ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9-87.2) pg/mL) compared to HC and IBS (30.7 (20.2 54.3), p<0.001 and 39.9 (25.9-68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3-93.0) pg/mL) and CD (63.8 (42.7-88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1-99.5) vs 40.0 (34.7-51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7-88.4) vs 48.4 (29.6-56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding. PMID- 27001945 TI - Development and validation of a composite score for excessive alcohol use screening. AB - This study was undertaken to develop a composite measure that combines the discriminant values of individual laboratory markers routinely used for excessive alcohol use (EAU) for an improved screening performance. The training sample consisted of 272 individuals with known history of EAU and 210 non-alcoholic individuals. The validation sample included 100 EAU and 75 controls. We used the estimated regression coefficients and the observed marker values to calculate the individual's composite screening score; this score was converted to a probability measure for excessive drinking in the given individual. A threshold value for the screening score based on an examination of the estimated sensitivity and specificity associated with different threshold values was proposed. Using regression coefficients estimated from the training sample, a composite score based on the levels of aspartate aminotransferase, alanine aminotransferase, per cent carbohydrate-deficient transferrin and mean corpuscular volume was calculated. The areas under the receiver operating characteristic curve (AUC) value of the selected model was 0.87, indicating a strong discriminating power and the AUC was better than that of each individual test. The score >0.23 corresponded to a sensitivity of 90% and a specificity of nearly 60%. The AUC value remained at a respectable level of 0.83 with the sensitivity and specificity at 91% and 49%, respectively, in the validation sample. We developed a novel composite score by using a combination of commonly used biomakers. However, the development of the mechanism-based biomarkers of EAU is needed to improve the screening and diagnosis of EAU in clinical practice. PMID- 27001946 TI - Restoring motor control and sensory feedback in people with upper extremity amputations using arrays of 96 microelectrodes implanted in the median and ulnar nerves. AB - OBJECTIVE: An important goal of neuroprosthetic research is to establish bidirectional communication between the user and new prosthetic limbs that are capable of controlling >20 different movements. One strategy for achieving this goal is to interface the prosthetic limb directly with efferent and afferent fibres in the peripheral nervous system using an array of intrafascicular microelectrodes. This approach would provide access to a large number of independent neural pathways for controlling high degree-of-freedom prosthetic limbs, as well as evoking multiple-complex sensory percepts. APPROACH: Utah Slanted Electrode Arrays (USEAs, 96 recording/stimulating electrodes) were implanted for 30 days into the median (Subject 1-M, 31 years post-amputation) or ulnar (Subject 2-U, 1.5 years post-amputation) nerves of two amputees. Neural activity was recorded during intended movements of the subject's phantom fingers and a linear Kalman filter was used to decode the neural data. Microelectrode stimulation of varying amplitudes and frequencies was delivered via single or multiple electrodes to investigate the number, size and quality of sensory percepts that could be evoked. Device performance over time was assessed by measuring: electrode impedances, signal-to-noise ratios (SNRs), stimulation thresholds, number and stability of evoked percepts. MAIN RESULTS: The subjects were able to proportionally, control individual fingers of a virtual robotic hand, with 13 different movements decoded offline (r = 0.48) and two movements decoded online. Electrical stimulation across one USEA evoked >80 sensory percepts. Varying the stimulation parameters modulated percept quality. Devices remained intrafascicularly implanted for the duration of the study with no significant changes in the SNRs or percept thresholds. SIGNIFICANCE: This study demonstrated that an array of 96 microelectrodes can be implanted into the human peripheral nervous system for up to 1 month durations. Such an array could provide intuitive control of a virtual prosthetic hand with broad sensory feedback. PMID- 27001947 TI - Designing the structure and folding pathway of modular topological bionanostructures. AB - Polypeptides and polynucleotides are programmable natural polymers whose linear sequence can be easily designed and synthesized by the cellular transcription/translation machinery. Nature primarily uses proteins as the molecular machines and nucleic acids as the medium for the manipulation of heritable information. A protein's tertiary structure and function is defined by multiple cooperative weak long-range interactions that have been optimized through evolution. DNA nanotechnology uses orthogonal pairwise interacting modules of complementary nucleic acids as a strategy to construct defined complex 3D structures. A similar approach has recently been applied to protein design, using orthogonal dimerizing coiled-coil segments as interacting modules. When concatenated into a single polypeptide chain, they self-assemble into the 3D structure defined by the topology of interacting modules within the chain. This approach allows the construction of geometric polypeptide scaffolds, bypassing the folding problem of compact proteins by relying on decoupled pairwise interactions. However, the folding pathway still needs to be optimized in order to allow rapid self-assembly under physiological conditions. Again the modularity of designed topological structures can be used to define the rules that guide the folding pathway of long polymers, such as DNA, based on the stability and topology of connected building modules. This approach opens the way towards incorporation of designed foldamers in biological systems and their functionalization. PMID- 27001948 TI - A novel semi-immersive virtual reality visuo-motor task activates ventrolateral prefrontal cortex: a functional near-infrared spectroscopy study. AB - OBJECTIVE: In the last few years, the interest in applying virtual reality systems for neurorehabilitation is increasing. Their compatibility with neuroimaging techniques, such as functional near-infrared spectroscopy (fNIRS), allows for the investigation of brain reorganization with multimodal stimulation and real-time control of the changes occurring in brain activity. The present study was aimed at testing a novel semi-immersive visuo-motor task (VMT), which has the features of being adopted in the field of neurorehabilitation of the upper limb motor function. APPROACH: A virtual environment was simulated through a three-dimensional hand-sensing device (the LEAP Motion Controller), and the concomitant VMT-related prefrontal cortex (PFC) response was monitored non invasively by fNIRS. Upon the VMT, performed at three different levels of difficulty, it was hypothesized that the PFC would be activated with an expected greater level of activation in the ventrolateral PFC (VLPFC), given its involvement in the motor action planning and in the allocation of the attentional resources to generate goals from current contexts. Twenty-one subjects were asked to move their right hand/forearm with the purpose of guiding a virtual sphere over a virtual path. A twenty-channel fNIRS system was employed for measuring changes in PFC oxygenated-deoxygenated hemoglobin (O2Hb/HHb, respectively). MAIN RESULTS: A VLPFC O2Hb increase and a concomitant HHb decrease were observed during the VMT performance, without any difference in relation to the task difficulty. SIGNIFICANCE: The present study has revealed a particular involvement of the VLPFC in the execution of the novel proposed semi-immersive VMT adoptable in the neurorehabilitation field. PMID- 27001949 TI - Spin manipulation in nanoscale superconductors. AB - The interplay of superconductivity and magnetism in nanoscale structures has attracted considerable attention in recent years due to the exciting new physics created by the competition of these antagonistic ordering phenomena, and the prospect of exploiting this competition for superconducting spintronics devices. While much of the attention is focused on spin-polarized supercurrents created by the triplet proximity effect, the recent discovery of long range quasiparticle spin transport in high-field superconductors has rekindled interest in spin dependent nonequilibrium properties of superconductors. In this review, the experimental situation on nonequilibrium spin injection into superconductors is discussed, and open questions and possible future directions of the field are outlined. PMID- 27001950 TI - Effect of Mn doping on ultrafast carrier dynamics in thin films of the topological insulator Bi2Se3. AB - Transient reflectivity (TR) measured at laser photon energy 1.51 eV from the indirectly intersurface-coupled topological insulator Bi2-x Mn x Se3 films (12 nm thick) revealed a strong dependence of the rise-time and initial decay-time constants on photoexcited carrier density and Mn content. In undoped samples (x = 0), these time constants are exclusively governed by electron-electron and electron-phonon scattering, respectively, whereas in films with x = 0.013-0.27 ultrafast carrier dynamics are completely controlled by photoexcited electron trapping by ionized Mn(2+) acceptors and their dimers. The shortest decay-time (~0.75 ps) measured for the film with x = 0.27 suggests a great potential of Mn doped Bi2Se3 films for applications in high-speed optoelectronic devices. Using Raman spectroscopy exploiting similar laser photon energy (1.58 eV), we demonstrate that due to indirect intersurface coupling in the films, the photoexcited electron trapping in the bulk enhances the electron-phonon interaction strength in Dirac surface states. PMID- 27001951 TI - Fano q-reversal in topological insulator Bi2Se3. AB - We studied the magneto-optical response of a canonical topological insulator Bi2Se3 with the goal of addressing a controversial issue of electron-phonon coupling. Magnetic-field induced modifications of reflectance are very pronounced in the infrared part of the spectrum, indicating strong electron-phonon coupling. This coupling causes an asymmetric line-shape of the 60 cm(-1) phonon mode, and is analyzed within the Fano formalism. The analysis reveals that the Fano asymmetry parameter (q) changes sign when the cyclotron resonance is degenerate with the phonon mode. To the best of our knowledge this is the first example of magnetic field driven q-reversal. PMID- 27001952 TI - TRAIL-coated lipid-nanoparticles overcome resistance to soluble recombinant TRAIL in non-small cell lung cancer cells. AB - PURPOSE: Non-small cell lung cancer (NSCLC) is one the types of cancer with higher prevalence and mortality. Apo2-Ligand/TRAIL is a TNF family member able to induce apoptosis in tumor cells but not in normal cells. It has been tested in clinical trials against different types of human cancer including NSCLC. However, results of clinical trials have shown a limited efficacy of TRAIL-based therapies. Recently we have demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) greatly improved TRAIL cytotoxic ability being capable of killing chemoresistant hematological cancer cells. In the present work we have extended the study to NSCLC. METHODS/PATIENTS: LUV-TRAIL induced cytotoxicity was assessed on different NSCLC cell lines with different sensitivity to soluble TRAIL and on primary human tumor cells from three patients suffering from NSCLC cancer. We also tested LUV-TRAIL-cytotoxic ability in combination with several anti-tumor agents. RESULTS: LUV-TRAIL exhibited a greater cytotoxic effect compared to soluble TRAIL both in A549 cells and primary human NSCLC cells. LUV-TRAIL-induced cell death was dependent on caspase-8 and caspase-3 activation. Moreover, combination of LUV-TRAIL with other anti-tumor agents such as flavopiridol, and SNS-032 clearly enhanced LUV-TRAIL-induced cytotoxicity against NSCLC cancer cells. CONCLUSION: The novel formulation of TRAIL based on displaying it on the surface of lipid nanoparticles greatly increases its anti-tumor activity and has clinical potential in cancer treatment. PMID- 27001953 TI - High-Resolution Longitudinal Study of HIV-1 Env Vaccine-Elicited B Cell Responses to the Virus Primary Receptor Binding Site Reveals Affinity Maturation and Clonal Persistence. AB - Because of the genetic variability of the HIV-1 envelope glycoproteins (Env), the elicitation of neutralizing Abs to conserved neutralization determinants including the primary receptor binding site, CD4 binding site (CD4bs), is a major focus of vaccine development. To gain insight into the evolution of Env-elicited Ab responses, we used single B cell analysis to interrogate the memory B cell Ig repertoires from two rhesus macaques after five serial immunizations with Env/adjuvant. We observed that the CD4bs-specific repertoire displayed unique features in the third CDR of Ig H chains with minor alterations along the immunization course. Progressive affinity maturation occurred as evidenced by elevated levels of somatic hypermutation (SHM) in Ab sequences isolated at the late immunization time point compared with the early time point. Abs with higher SHM were associated with increased binding affinity and virus neutralization capacity. Moreover, a notable portion of the CD4bs-specific repertoire was maintained between early and late immunization time points, suggesting that persistent clonal lineages were induced by Env vaccination. Furthermore, we found that the predominant persistent CD4bs-specific clonal lineages had larger population sizes and higher affinities than that from the rest of the repertoires, underscoring the critical role of Ag affinity selection in Ab maturation and clonal expansion. Genetic and functional analyses revealed that the accumulation of SHM in both framework regions and CDRs contributed to the clonal affinity and antigenicity evolution. Our longitudinal study provides high resolution understanding of the dynamically evolving CD4bs-specific B cell response after Env immunization in primates. PMID- 27001955 TI - Topical Application of Fingolimod Perturbs Cutaneous Inflammation. AB - The prevalence of allergies, including rhinitis, eczema, and anaphylaxis, is rising dramatically worldwide. This increase is especially problematic in children who bear the greatest burden of this rising trend. Increasing evidence identifies neutrophils as primary perpetrators of the more severe and difficult to manage forms of inflammation. A newly recognized mechanism by which neutrophils are recruited during the early phase of histamine-induced inflammation involves the sphingosine kinase (SK)/sphingosine-1-phosphate axis. This study examines whether topical application of fingolimod, an established SK/sphingosine-1-phosphate antagonist already in clinical use to treat multiple sclerosis, may be repurposed to treat cutaneous inflammation. Using two mouse models of ear skin inflammation (histamine- and IgE-mediated passive cutaneous anaphylaxis) we topically applied fingolimod prophylactically, as well as after establishment of the inflammatory response, and examined ear swelling, SK activity, vascular permeability, leukocyte recruitment, and production of proinflammatory mediators. The present study reveals that when applied topically, fingolimod attenuates both immediate and late-phase responses to histamine with reduced extravasation of fluid, SK-1 activity, proinflammatory cytokine and chemokine production, and neutrophil influx and prevents ear swelling. Intravital microscopy demonstrates that histamine-induced neutrophil rolling and adhesion to the postcapillary venules in the mouse ears is significantly attenuated even after 24 h. More importantly, these effects are achievable even once inflammation is established. Translation into humans was also accomplished with epicutaneous application of fingolimod resolving histamine-induced and allergen-induced inflammatory reactions in forearm skin. Overall, this study demonstrates, to our knowledge for the first time, that fingolimod may be repurposed to treat cutaneous inflammation. PMID- 27001954 TI - TGF-beta-Induced Regulatory T Cells Directly Suppress B Cell Responses through a Noncytotoxic Mechanism. AB - Foxp3(+) regulatory T cells (Treg) playing a crucial role in the maintenance of immune tolerance and prevention of autoimmune diseases consist of thymus-derived naturally occurring CD4(+)Foxp3(+) Treg cells (nTreg) and those that can be induced ex vivo with TGF-beta (iTreg). Although both Treg subsets share similar phenotypes and functional characteristics, they also have potential biologic differences on their biology. The role of iTreg in regulating B cells remains unclear so far. The suppression assays of Treg subsets on activation, proliferation, and Abs production of B cells were measured using a Treg and B cell coculture system in vitro. Transwell and Ab blockade experiments were performed to assess the roles of cell contact and soluble cytokines. Treg were adoptively transferred to lupus mice to assess in vivo effects on B cells. Like nTreg, iTreg subset also directly suppressed activation and proliferation of B cells. nTreg subset suppressed B cell responses through cytotoxic manner related to expression of granzyme A, granzyme B, and perforin, whereas the role of iTreg subset on B cells did not involve in cytotoxic action but depending on TGF-beta signaling. Furthermore, iTreg subset can significantly suppress Ab produced by lupus B cells in vitro. Comparison experiments using autoantibodies microarrays demonstrated that adoptive transfer of iTreg had a superior effect than nTreg subset on suppressing lupus B cell responses in vivo. Our data implicate a role and advantage of iTreg subset in treating B cell-mediated autoimmune diseases, boosting the translational potential of these findings. PMID- 27001956 TI - Subcutaneous Allergic Sensitization to Protease Allergen Is Dependent on Mast Cells but Not IL-33: Distinct Mechanisms between Subcutaneous and Intranasal Routes. AB - Protease activity of papain, a plant-derived occupational allergen homologous to mite major allergens, is essential to IgE/IgG1 production and lung eosinophilia induced by intranasal papain administration in mice, and IL-33 contributes to these responses. In this work, we investigate skin and Ab responses induced by s.c. papain administration into ear lobes and responses induced by subsequent airway challenge with papain. Subcutaneous papain injection induced swelling associated with increased epidermal thickness, dermal inflammation, serum IgE/IgG1 responses, and Th2 cytokine production in draining lymph node cells restimulated in vitro. These responses were markedly less upon s.c. administration of protease inhibitor-treated papain. Results obtained by using mast cell-deficient mice and reconstitution of tissue mast cells suggested the contribution of mast cells to papain-specific IgE/IgG1 responses and eosinophil infiltration. The responses were equivalent between wild-type and IL-33(-/-) mice. After the subsequent airway challenge, the s.c. presensitized wild-type mice showed more severe lung eosinophilia than those without the presensitization. The presensitized IL-33(-/-) mice showed modest lung eosinophilia, which was absent without the presensitization, but its severity and IgE boost by the airway challenge were markedly less than the presensitized wild type mice, in which protease activity of inhaled papain contributed to the responses. The results suggest that mechanisms for the protease-dependent sensitization differ between skin and airway and that cooperation of mast cell dependent, IL-33-independent initial sensitization via skin and protease-induced, IL-33-mediated mechanism in re-exposure via airway to protease allergens maximizes the magnitude of the transition from skin inflammation to asthma in natural history of progression of allergic diseases. PMID- 27001957 TI - IL-15-Independent Maintenance of Tissue-Resident and Boosted Effector Memory CD8 T Cells. AB - IL-15 regulates central and effector memory CD8 T cell (TCM and TEM, respectively) homeostatic proliferation, maintenance, and longevity. Consequently, IL-15 availability hypothetically defines the carrying capacity for total memory CD8 T cells within the host. In conflict with this hypothesis, previous observations demonstrated that boosting generates preternaturally abundant TEM that increases the total quantity of memory CD8 T cells in mice. In this article, we provide a potential mechanistic explanation by reporting that boosted circulating TEM do not require IL-15 for maintenance. We also investigated tissue-resident memory CD8 T cells (TRM), which protect nonlymphoid tissues from reinfection. We observed up to a 50-fold increase in the total magnitude of TRM in mouse mucosal tissues after boosting, suggesting that the memory T cell capacity in tissues is flexible and that TRM may not be under the same homeostatic regulation as primary central memory CD8 T cells and TEM Further analysis identified distinct TRM populations that depended on IL-15 for homeostatic proliferation and survival, depended on IL-15 for homeostatic proliferation but not for survival, or did not depend on IL-15 for either process. These observations on the numerical regulation of T cell memory indicate that there may be significant heterogeneity among distinct TRM populations and also argue against the common perception that developing vaccines that confer protection by establishing abundant TEM and TRM will necessarily erode immunity to previously encountered pathogens as the result of competition for IL-15. PMID- 27001959 TI - Deterministic radiative coupling between plasmonic nanoantennas and semiconducting nanowire quantum dots. AB - We report on the deterministic coupling between single semiconducting nanowire quantum dots emitting in visible and plasmonic Au nanoantennas. Both systems are separately and carefully characterized through micro-photoluminescence and cathodoluminescence. A two-step realignment process using cathodoluminescence allows for electron-beam lithography of Au antennas near individual nanowire quantum dots with a precision of 50 nm. A complete set of optical properties was measured before and after antenna fabrication. They evidence both an increase of the nanowire absorption, and an improvement of the quantum dot emission rate up to a factor of two in presence of the antenna. PMID- 27001958 TI - Cutting Edge: Foxp1 Controls Naive CD8+ T Cell Quiescence by Simultaneously Repressing Key Pathways in Cellular Metabolism and Cell Cycle Progression. AB - Previously we have shown that transcription factor Foxp1 plays an essential role in maintaining naive T cell quiescence; in the absence of Foxp1, mature naive CD8(+) T cells proliferate in direct response to homeostatic cytokine IL-7. In this study, we report that the deletion of Foxp1 in naive CD8(+) T cells leads to enhanced activation of the PI3K/Akt/mammalian target of rapamycin signaling pathway and its downstream cell growth and metabolism targets in response to IL 7. We found that Foxp1 directly regulates PI3K interacting protein 1, a negative regulator of PI3K. Additionally, we found that deletion of Foxp1 in naive CD8(+) T cells results in increased expression levels of E2fs, the critical components for cell cycle progression and proliferation, in a manner that is not associated with increased phosphorylation of retinoblastoma protein. Taken together, our studies suggest that Foxp1 enforces naive CD8(+) T cell quiescence by simultaneously repressing key pathways in both cellular metabolism and cell cycle progression. PMID- 27001963 TI - Bmo-miR-2758 Targets BmFMBP-1 (Lepidoptera: Bombycidae) and Suppresses Its Expression in BmN Cells. AB - MicroRNAs (miRNAs) are an abundant family of endogenous noncoding small RNA molecules. They play crucial roles on regulation of life processes both in plants and animals. Fibroin modulator binding protein-1 (FMBP-1) is a silk gland transcription factor of Bombyx mori, which is considered as a trans-activator of fibroin genes. And bioinformatics prediction showed that at the 3' untranslated region (3' UTR) of BmFMBP-1 there were binding sites for three bmo-miRNAs, bmo miR-2b*, bmo-miR-305, and bmo-miR-2758, separately. In order to validate whether these bmo-miRNAs involved in the regulation of BmFMBP-1 expression, the expression levels of three bmo-miRNAs and BmFMBP-1 in the middle silk gland (MSG) and posterior silk gland (PSG) during the fourth- and fifth-larval stages of B. mori were measured by semi-quantitative reverse transcription polymerase chain reaction. The results revealed that the expression level of bmo-miR-2758 was the highest in the three, and it expressed higher in the PSG than in the MSG with a similar expression pattern as BmFMBP-1, implying that bmo-miR-2758 may involved in regulation of BmFMBP-1. To validate the regulation function of bmo-miR-2758 on BmFMBP-1, recombinant plasmids pcDNA3 [ie1-egfp-pri-bmo-miR-2758-SV40] and pGL3 [A3-luc-FMBP-1 3' UTR-SV40] were constructed and co-transfected in BmN cells. The dual-luciferase reporter assay system was used for assay of transient expression. The results showed that the expression of the luciferase reporter was significantly decreased when pGL3 [A3-luc-FMBP-1 3' UTR-SV40] co-transfected with pcDNA3 [ie1-egfp-pri-bmo-miR-2758-SV40] (P < .01). Furthermore, when the artificial antisense RNA of bmo-miR-2758 (inhibitor) was added to the above co transfection, the expression of the luciferase reporter was recovered significantly (P < 0.01). These results suggest that bmo-miR-2758 represses the expression of BmFMBP-1 in vitro. PMID- 27001960 TI - Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus. AB - BACKGROUND: Vaccination and passive antibody therapies are critical for controlling infectious diseases. Passive antibody administration has limitations, including the necessity for purification and multiple injections for efficacy. Vaccination is associated with a lag phase before generation of immunity. Novel approaches reported here utilize the benefits of both methods for the rapid generation of effective immunity. METHODS: A novel antibody-based prophylaxis/therapy entailing the electroporation-mediated delivery of synthetic DNA plasmids encoding biologically active anti-chikungunya virus (CHIKV) envelope monoclonal antibody (dMAb) was designed and evaluated for antiviral efficacy, as well as for the ability to overcome shortcomings inherent with conventional active vaccination and passive immunotherapy. RESULTS: One intramuscular injection of dMAb produced antibodies in vivo more rapidly than active vaccination with an anti-CHIKV DNA vaccine. This dMAb neutralized diverse CHIKV clinical isolates and protected mice from viral challenge. Combination of dMAb and the CHIKV DNA vaccine afforded rapid and long-lived protection. CONCLUSIONS: A DNA-based dMAb strategy induced rapid protection against an emerging viral infection. This method can be combined with DNA vaccination as a novel strategy to provide both short- and long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment and control strategies. PMID- 27001964 TI - Abundance and Frequency of the Asiatic Oak Weevil (Coleoptera: Curculionidae) and Defoliation on American, Chinese, and Hybrid Chestnut (Castanea). AB - The Asiatic oak weevil, Cyrtepistomus castaneus Roelofs (Coleoptera: Curculionidae), is a nonnative defoliator of trees in the Fagaceae family in the United States but has not been studied on Castanea species in the southern Appalachian Mountains. Planted trees of Castanea dentata (Marsh.) Borkh. (Fagales: Fagaceae), Castanea mollissima Blume (Fagales: Fagaceae), and four hybrid breeding generations were evaluated in 2012 for insect defoliation and C. castaneus abundance and frequency. Defoliation was visually assessed throughout the growing season at two sites in the southern Appalachian Mountains (western North Carolina and eastern Tennessee). C. castaneus abundance and frequency were monitored on trees using beat sheets and emergence was recorded from ground traps. Asiatic oak weevils were more abundant and more frequently collected on American chestnut (Ca. dentata) and its most closely related BC3F3 hybrid generation than on the Asian species Ca. mollissima. In most months, C. castaneus colonization of hybrid generations was not significantly different than colonization of parental species. Frequency data for C. castaneus suggested that adults were distributed relatively evenly throughout the study sites rather than in dense clusters. Emergence of C. castaneus was significantly higher under a canopy dominated by Quercus species than under non-Quercus species or open sky. C. castaneus emergence began in May and peaked in late June and early July. These results may be useful for resource managers trying to restore blight-resistant chestnut to the Southern Appalachians while minimizing herbivory by insect pests. PMID- 27001965 TI - Treatment Effect of Clopidogrel Plus Aspirin Within 12 Hours of Acute Minor Stroke or Transient Ischemic Attack. AB - BACKGROUND: The aim of this study was to analyze the benefits and safety associated with the combination therapy of clopidogrel and aspirin among minor stroke or transient ischemic attack patients treated within 12 hours. METHODS AND RESULTS: This was a subanalysis of the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial, mainly limited to the prespecified group of patients randomized within 12 hours to either the combination of clopidogrel plus aspirin or aspirin alone. The primary outcome was ischemic stroke during 90-day follow-up. Recurrent ischemic stroke and progressive ischemic stroke were analyzed. Multivariable Cox modeling showed that randomization within 12 hours was an independent predictor of ischemic stroke events (hazard ratio [95% CI] 1.25 [1.04-1.49], P=0.02). Among 2573 patients randomized within 12 hours, 282 (10.96%) patients had ischemic stroke events. Among them, 158 (12.34%) of 1280 patients taking aspirin experienced ischemic stroke compared with 124 (9.59%) of 1293 patients taking clopidogrel-aspirin (P=0.02). The dual antiplatelet was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke (6.57% versus 8.91%, P=0.03) but not progressive ischemic stroke (3.02% versus 3.43%, P=0.28). There was no significant difference in hemorrhagic events (P=0.39). CONCLUSIONS: Among patients treated within 12 hours, the combination of clopidogrel and aspirin was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke during the 90-day follow-up and did not increase the hemorrhagic risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00979589. PMID- 27001966 TI - Interplay Between the Effects of Dilated Cardiomyopathy Mutation (R206L) and the Protein Kinase C Phosphomimic (T204E) of Rat Cardiac Troponin T Are Differently Modulated by alpha- and beta-Myosin Heavy Chain Isoforms. AB - BACKGROUND: We hypothesized that the functional effects of R206L-a rat analog of the dilated cardiomyopathy (DCM) mutation R205L in human cardiac troponin T (TnT) were differently modulated by myosin heavy chain (MHC) isoforms and T204E, a protein kinase C (PKC) phosphomimic of TnT. Our hypothesis was based on two observations: (1) alpha- and beta-MHC differentially influence the functional effects of TnT; and (2) PKC isoforms capable of phosphorylating TnT are upregulated in failing human hearts. METHODS AND RESULTS: We generated 4 recombinant TnT variants: wild type; R206L; T204E; and R206L+T204E. Functional effects of the TnT variants were tested in cardiac muscle fibers (minimum 14 per group) from normal (alpha-MHC) and propylthiouracil-treated rats (beta-MHC) using steady-state and dynamic contractile measurements. Notably, in alpha-MHC fibers, Ca(2+)-activated maximal tension was attenuated by R206L (~32%), T204E (~63%), and R206L+T204E (~64%). In beta-MHC fibers, maximal tension was unaffected by R206L, but was attenuated by T204E (~33%) and R206L+T204E (~40%). Thus, beta-MHC differentially counteracted the attenuating effects of the TnT variants on tension. However, in beta-MHC fibers, R206L+T204E attenuated tension to a greater extent when compared to T204E alone. In beta-MHC fibers, R206L+T204E attenuated the magnitude of the length-mediated recruitment of new cross-bridges (~28%), suggesting that the Frank-Starling mechanism was impaired. CONCLUSIONS: Our findings are the first (to our knowledge) to demonstrate that the functional effects of a DCM-linked TnT mutation are not only modulated by MHC isoforms, but also by the pathology-associated post-translational modifications of TnT. PMID- 27001968 TI - Uterine natural killer cell partnerships in early mouse decidua basalis. AB - The decidua basalis of developing mouse implantation sites is highly enriched in CD45+ leukocytes. In intact, syngeneically mated C57BL/6 decidua basalis examined at gestation day 8.5 by whole-mount in situ immunohistochemistry, leukocyte, but not trophoblast, conjugations were reported. Nothing is known regarding time course, frequency, composition, or importance of physiologic decidual CD45+ cell pairing. In this study, we confirmed the presence of anti-CD54+/anti-CD11a+ immune synapses in CD45+ decidual cell conjugates and characterized their cellular heterogeneity. Conjugated cell pairs were virtually absent before implantation (virgin and gestation days 3.5 and 4.5), were infrequent at gestation day 5.5, but involved 19% of all CD45+ cells by gestation day 8.5, then declined. By gestation day 8.5, almost all CD45+ cells coexpressed CD31, and 2 CD45+CD31+ cells composed most conjugates. Conjugation partners were defined for 2 nonoverlapping uterine natural killer cell subsets (Ly49C/I +/Dolichos biflorus agglutinin lectin- and Ly49C/I-/Dolichos biflorus agglutinin lectin+). Ly49C/I+ uterine natural killer cells were the major subset from before mating up to gestation day 6.5. At gestation day 5.5/6.5, uterine natural killer cell conjugates involving Ly49C/I + cells were more abundant. By gestation day 8.5/9.5, Dolichos biflorus agglutinin lectin+ uterine natural killer cells were the dominant subset with Dolichos biflorus agglutinin lectin+/Dolichos biflorus agglutinin lectin+ homologous conjugates and Dolichos biflorus agglutinin lectin+/Dolichos biflorus agglutinin lectin- heterologous conjugates dominating uterine natural killer cell pairings. At gestation day 6.5, both Ly49C/I+/CD45+ and Dolichos biflorus agglutinin lectin+/CD45+ heterologous conjugate pairs strongly engaged antigen-presenting cells (CD11c+, CD68+, or major histocompatibility complex class II+). By gestation day 8.5, dominant partners of Ly49C/I+/CD45+ and Dolichos biflorus agglutinin lectin+/CD45+ heterologous conjugates are T cells (CD8+ >CD4+). Heterologous conjugates that did not involve uterine natural killer cells occurred but did not suggest antigen presentation to T cells. These data identify gestation day 6.5-8.5 in the pregnant mouse as a critical window for leukocyte interactions that may establish immune regulation within implantation sites. PMID- 27001967 TI - Tetrahydrobiopterin Protects Against Hypertrophic Heart Disease Independent of Myocardial Nitric Oxide Synthase Coupling. AB - BACKGROUND: Nitric oxide synthase uncoupling occurs under conditions of oxidative stress modifying the enzyme's function so it generates superoxide rather than nitric oxide. Nitric oxide synthase uncoupling occurs with chronic pressure overload, and both are ameliorated by exogenous tetrahydrobiopterin (BH4)-a cofactor required for normal nitric oxide synthase function-supporting a pathophysiological link. Genetically augmenting BH4 synthesis in endothelial cells fails to replicate this benefit, indicating that other cell types dominate the effects of exogenous BH4 administration. We tested whether the primary cellular target of BH4 is the cardiomyocyte or whether other novel mechanisms are invoked. METHODS AND RESULTS: Mice with cardiomyocyte-specific overexpression of GTP cyclohydrolase 1 (mGCH1) and wild-type littermates underwent transverse aortic constriction. The mGCH1 mice had markedly increased myocardial BH4 and, unlike wild type, maintained nitric oxide synthase coupling after transverse aortic constriction; however, the transverse aortic constriction-induced abnormalities in cardiac morphology and function were similar in both groups. In contrast, exogenous BH4 supplementation improved transverse aortic constricted hearts in both groups, suppressed multiple inflammatory cytokines, and attenuated infiltration of inflammatory macrophages into the heart early after transverse aortic constriction. CONCLUSIONS: BH4 protection against adverse remodeling in hypertrophic cardiac disease is not driven by its prevention of myocardial nitric oxide synthase uncoupling, as presumed previously. Instead, benefits from exogenous BH4 are mediated by a protective effect coupled to suppression of inflammatory pathways and myocardial macrophage infiltration. PMID- 27001970 TI - microRNA-129-5p, a c-Myc negative target, affects hepatocellular carcinoma progression by blocking the Warburg effect. AB - Deregulation of microRNAs (miRNAs) and c-Myc (Myc) contributes to hepatocellular carcinoma (HCC) progression, but how miRNAs and Myc regulate each other in hepatocarcinogenesis is still poorly understood. Using a functional screen, we identified miR-129-5p as a miRNA that inhibits HCC cell growth. miR-129-5p targets the mitochondrial matrix protein pyruvate dehydrogenase kinase 4 (PDK4), which leads to decreased phosphorylation of the E1alpha subunit of pyruvate dehyrogenase (PDH) complex, inhibition of glycolysis, retarded tumor growth, and impaired lung colonization. Enforced expression of PDK4 refractory to inhibition by miR-129-5p rescued all of these phenotypes. Targeting PDK4 by shRNA recapitulated the effects caused by miR-129-5p. miR-129-5p is transcriptionally repressed by a complex comprised of Myc, histone deacetylase 3 (HDAC3), and enhancer of zeste 2 polycomb repressive complex 2 (EZH2). Levels of miR-129-5p negatively correlated with clinical stages in human HCC. Restoring miR-129-5p expression suppressed the diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. Thus, we concluded that miR-129-5p, which is a negative target of Myc, blocks glycolysis to retard hepatocarcinogenesis via targeting PDK4. The critical link between miR-129-5p and PDK4 in the progression of HCC suggests potential points of therapeutic intervention for this disease. PMID- 27001969 TI - Arterial Stiffening in Perspective: Advances in Physical and Physiological Science Over Centuries. AB - Arterial stiffening is not a new issue in medicine or research but was the prime concern of Richard Bright in the early 19th century and of the prominent London physicians and pathologists who tried to unscramble the relationship between kidney, heart, and cerebrovascular disease and hardness of the pulse in the late 19th century. It was of major concern to medical educators including Osler and Mackenzie who were still active in practice 100 years ago. It is all too easy (when dependent on the Internet) to consider arterial stiffness to be a new issue. The terms arterial stiffness, aortic stiffness, or wave reflection do not appear as categories for articles such as this in respectable journals, nor in categories for meetings of specialized physicians. Yet as described in this article, the subject was of interest to clinicians, to investigators such as Harvey in the 17th century, and to physicists who developed laws and principles of elasticity from the study of biological materials including ligaments and arteries. This paper provides a perspective on arterial stiffness from the time of William Harvey and Isaac Newton to the present, with a glance into the future. PMID- 27001971 TI - Personalized evaluation based on quantitative proteomics for drug-treated patients with chronic kidney disease. AB - The patient's response to drug treatment is usually systems-wide based on multi spots through either direct or indirect targets. Thus, the evaluation of the treatment cannot rely on single targeted biomarker, especially for complex diseases such as chronic kidney disease. In the present study, we performed a systems-wide analysis using proteomic approach to quantify changes in the proteomic profiles of the plasma from IgA nephropathy (IgAN) patients before and after treatment. In particular, the patient-to-health distances based on global proteome quantification before and after treatment were calculated and considered as quantitative readouts to measure patient divergences from the healthy condition. We found that the patient-to-health distance nicely correlated with the patient's response to drug treatment and long-term prognosis, which created a self-tracking platform for personalized evaluation. In addition, the steroid treatment plays a role in immunosuppression, while the Chinese Traditional Medicine (TCM) can modulate whole-body systems. Our results indicated that STC therapy normalized the proteomic profile more significantly than SA therapy. This work provides an omics-based and systematic platform for personalized evaluation of disease treatment. This strategy could help us to evaluate treatment outcomes and predict prognosis in patients with IgAN and other complex diseases. PMID- 27001972 TI - Development of an inducible transposon system for efficient random mutagenesis in Clostridium acetobutylicum. AB - Clostridium acetobutylicum is an industrially important Gram-positive organism, which is capable of producing economically important chemicals in the ABE (Acetone, Butanol and Ethanol) fermentation process. Renewed interests in the ABE process necessitate the availability of additional genetics tools to facilitate the derivation of a greater understanding of the underlying metabolic and regulatory control processes in operation through forward genetic strategies. In this study, a xylose inducible, mariner-based, transposon system was developed and shown to allow high-efficient random mutagenesis in the model strain ATCC 824. Of the thiamphenicol resistant colonies obtained, 91.9% were shown to be due to successful transposition of the catP-based mini-transposon element. Phenotypic screening of 200 transposon clones revealed a sporulation-defective clone with an insertion in spo0A, thereby demonstrating that this inducible transposon system can be used for forward genetic studies in C. acetobutylicum. PMID- 27001973 TI - Xanthomonas oryzae pv. oryzae requires H-NS-family protein XrvC to regulate virulence during rice infection. AB - Histone-like nucleoid-structuring (H-NS) proteins, which are conserved in Gram negative bacteria, bind DNA and act as the global transcriptional repressors. In this study, we identified and characterized the xrvC gene encoding a H-NS protein in Xathomonas oryzae pv. oryzae (Xoo) Philippines strain PXO99(A) Compared with the wild type, the xrvC-deficient mutant of PXO99(A) (named PXO99DeltaxrvC) showed a reduced growth rate in both nutrient-rich and nutrient-limited media. Interestingly, PXO99DeltaxrvC exhibited significantly reduced virulence on rice cultivar IRBB214, but its virulence on 31 other rice cultivars was not affected. Transcriptional analysis revealed that the expression of hrpG, hrpX and hpa1 and of 15 out of 18 tested non-TAL (transcription activator-like) effector genes was decreased significantly in the xrvC mutant compared with that in the wild type. In addition, loss of xrvC also impaired the induction of the rice susceptibility gene Os8N3 in IRBB214 by PXO99(A) Our results suggest that the xrvC gene is involved in bacterial growth, and it plays a vital role in virulence by positively regulating the expression of hrp genes and non-TAL effector genes in PXO99(A) and the susceptibility gene Os8N3 in rice. PMID- 27001974 TI - Possible Brain Mechanisms of Creativity. AB - Creativity is the new discovery, understanding, development and expression of orderly and meaningful relationships. Creativity has three major stages: preparation, the development (nature and nurture) of critical knowledge and skills; innovation, the development of a creative solution; and creative production. Successful preparation requires a basic level of general intelligence and domain specific knowledge and skills and highly creative people may have anatomic alterations of specific neocortical regions. Innovation requires disengagement and divergent thinking primarily mediated by frontal networks. Creative people are often risk-takers and novelty seekers, behaviors that activate their ventral striatal reward system. Innovation also requires associative and convergent thinking, activities that are dependent on the integration of highly distributed networks. People are often most creative when they are in mental states associated with reduced levels of brain norepinephrine, which may enhance the communication between distributed networks. We, however, need to learn more about the brain mechanisms of creativity. PMID- 27001975 TI - Therapeutic expansion of CD4+FoxP3+ regulatory T cells limits allergic airway inflammation during pulmonary fungal infection. AB - Allergic asthma can be frequently caused and exacerbated by sensitization to ubiquitous fungal allergens associated with pulmonary mucus production, airway hyperresponsiveness and bronchial constriction, resulting in a complex disease that is often difficult to treat. Fungal infections are frequently complicated by the development of a type 2 immune response that prevents successful elimination of the fungal pathogen. Furthermore, production of type 2 cytokines triggers allergic airway inflammation. Following intranasal infection of BALB/c mice with the fungusCryptococcus neoformans, we recently described a more pronounced type 2 immune response in the absence of regulatory T (Treg) cells. To determine whether Treg cell expansion is able to suppress type 2-related fungal allergic inflammation, we increased Treg cell numbers during pulmonaryC. neoformansinfection by administration of an interleukin (IL)-2/anti-IL-2 complex. Expansion of Treg cells resulted in reduced immunoglobulin E production and decreased allergic airway inflammation including reduced production of pulmonary mucus and type 2 cytokines as well as production of immunosuppressive cytokines such as IL-10 and transforming growth factor-beta1. From our data we conclude that Treg cells and/or their suppressive mediators represent potential targets for therapeutic intervention during allergic fungal airway disease. PMID- 27001978 TI - Compounding oversight a work in progress for states, FDA. PMID- 27001976 TI - Comparative analysis of sequences, polymorphisms and topology of yeasts aquaporins and aquaglyceroporins. AB - Efficient homeostasis of water and glycerol is a prerequisite for osmoregulation and other aspects of yeasts life. The cellular status of these molecules is often associated with functional presence of aquaporins and aquaglyceroporins. The present study provides a detailed updated analysis of aquaporins and aquaglyceroporins in 47 yeast species. A comprehensive analysis of aquaporins and aquaglyceroporins in 38 strains of Saccharomyces cerevisiae from different ecological niches is also presented. The functionality of specific aquaporins in yeasts has been associated with their adaptation requirements in different environmental conditions. In the present study, various inactivating mutations in aquaporin sequences were found in strains of S. cerevisiae Likewise, several new interesting polymorphisms in aquaglyceroporin sequences of some commercial wine and brewing strains, vineyard and bakery strains were also observed. Conceivably, both in the case of aquaporins and aquaglyceroporins inactivating mutations resulted in competitive advantage in selected environments. Topology and conservation of important regulatory residues within all sequences are also analyzed. We expect that the present review may contribute to establish the functional relevance of aquaporins/aquaglyceroporins for various aspects of yeasts physiology. PMID- 27001979 TI - Pharmacy adopts "universal precautions" for medication lists. PMID- 27001980 TI - Midwest healthcare group puts pharmacists in patients' homes. PMID- 27001981 TI - The pharmacist: An indispensable partner in HIV care. PMID- 27001982 TI - Individualization of resident orientation for nontraditional pharmacy residents. PMID- 27001983 TI - Cultivating statistical knowledge in pharmacy residents' research. PMID- 27001984 TI - Implementation of clinical decision support rules. PMID- 27001985 TI - Panobinostat: A histone deacetylase inhibitor for the treatment of relapsed or refractory multiple myeloma. AB - PURPOSE: The mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, interaction potential, adverse effects, and place in therapy of panobinostat are reviewed. SUMMARY: Panobinostat (Farydak, Novartis) is a novel pan-deacetylase inhibitor approved for use in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) who have received at least two regimens containing an immunomodulatory drug and bortezomib. National Comprehensive Cancer Network (NCCN) guidelines recommend the use of panobinostat plus bortezomib and dexamethasone as a preferred regimen for previously treated multiple myeloma (MM). A Phase III trial comparing panobinostat or placebo use in combination with bortezomib and dexamethasone demonstrated improved median progression-free survival in the panobinostat group (11.99 months [95% CI, 10.33-12.94 months] versus 8.08 months [95% CI, 7.56-9.23 months]; hazard ratio, 0.63 [95% CI, 0.52-0.76]; p < 0.0001), as well as a significantly higher rate of complete or near complete response (27.6% [95% CI, 23.2-32.4%] versus 15.7% [95% CI, 12.2-19.8%]; p = 0.00006). Common grade 3 or 4 laboratory abnormalities and adverse events associated with panobinostat include thrombocytopenia, lymphopenia, diarrhea, asthenia, fatigue, and peripheral neuropathy. CONCLUSION: Panobinostat is a promising alternative to well-studied, NCCN-recommended regimens for the treatment of RRMM. It has demonstrated efficacy when used in combination with bortezomib and dexamethasone for the treatment of patients with MM who have received at least two prior regimens including bortezomib and an immunomodulatory agent. Despite the observed benefits, concern regarding toxicity may limit panobinostat use in practice. PMID- 27001986 TI - Prevention of perinatal transmission of zidovudine- and nevirapine-resistant HIV. AB - PURPOSE: The use of a three-drug regimen for the prevention of perinatal transmission of zidovudine- and nevirapine-resistant HIV is described. SUMMARY: A 17-year-old Hispanic woman infected with HIV arrived at our clinic for the management of her first pregnancy. The patient was in her second trimester of her pregnancy, had not previously been treated with antiretroviral therapy, and was only taking daily prenatal vitamins at the time of her first clinic visit. Her HIV RNA viral load was 240 copies/mL, and the virus was resistant to both zidovudine and nevirapine. Nelfinavir (compounded suspension), lamivudine, and zidovudine were prescribed for the mother, though she was generally nonadherent to therapy. Nelfinavir, lamivudine, and zidovudine were initiated for the newborn within eight hours of delivery. Six months later, the patient returned to the clinic in the first trimester of her second pregnancy. At this visit, her HIV RNA viral load was 120 copies/mL. After the birth of her second child, the infant received the same regimen received by her firstborn: zidovudine 4 mg/kg orally twice daily for six weeks, lamivudine 2 mg/kg orally twice daily for two weeks, and nelfinavir 55 mg/kg orally twice daily for two weeks. At four months of age, each infant was found to be HIV-negative. CONCLUSION: A prophylactic regimen that included nelfinavir, lamivudine, and zidovudine was used to prevent perinatal transmission of HIV in two neonates. The regimen was well tolerated, and both infants were determined to be HIV-negative at four months of age. PMID- 27001987 TI - Economic and patient satisfaction outcomes of a layered learning model in a small community hospital. AB - PURPOSE: Results of a study of economic and patient satisfaction outcomes of implementing a "layered learning model" (LLM) in a community hospital are presented. METHODS: An LLM consisting of a clinical pharmacist, two postgraduate year 1 pharmacy residents, and pharmacy students participating in rounds and providing patient education was implemented at a small community hospital. The primary endpoint was the difference in mean total drug cost per discharge in cases managed by physicians who rounded with pharmacy representatives (the intervention group) and cases managed by physicians who rounded with no pharmacist present (the control group). Secondary outcomes were drug expenditures associated with eight common diagnoses and patient satisfaction scores in medication education domains of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. Statistical analysis was performed using Student's t test and chi-square tests. RESULTS: The intervention-group data comprised 2737 hospital discharges, as compared with 3983 discharges for the control group. The geometric mean total drug cost per discharge was $161.52 for the intervention group, as compared with $210.15 for the control group (difference, $48.63; p < 0.001); drug costs for pneumonia and urinary tract infection were significantly lower for the intervention group. Patient satisfaction scores were significantly improved in the intervention group relative to baseline scores (8th percentile versus 39th percentile, p < 0.001). CONCLUSION: Implementation of the LLM in a small community hospital reduced medication costs and improved HCAHPS patient satisfaction scores. PMID- 27001988 TI - Implementation of a new dantrolene formulation across a multifacility health system. AB - PURPOSE: An initiative to optimize the treatment of malignant hyperthermia in surgical patients through a dantrolene product conversion program is described. SUMMARY: A large health system's formulary evaluation of a new dantrolene sodium product indicated that despite a higher cost per treatment course, the product could offer key advantages over older formulations of dantrolene in terms of preparation and administration time, product content, and storage requirements. A work group, consisting of pharmacy personnel, an anesthesiologist, a nurse anesthetist, and a representative of the health system's group purchasing organization, determined that a switch to the new dantrolene product would offer both patient care benefits and process benefits. With the approval of the health system's pharmacy and therapeutics committee, the new product was added to the formulary as the preferred dosage form of dantrolene, and existing dantrolene product stock was converted to the new formulation. Key implementation steps included (1) concurrent replacement of dantrolene stock on all "malignant hyperthermia carts" across the 15-hospital health system, (2) development of educational materials to raise awareness of the conversion and revised product preparation procedures, (3) anesthesiology provider and pharmacy staff education, (4) revision of dantrolene listings in each hospital's computerized prescriber order-entry system, and (5) redistribution of returned dantrolene product stock. The dantrolene product conversion occurred over a four-month period. CONCLUSION: A multifacility health system was successful in converting an existing stock of dantrolene to a newly available formulation. PMID- 27001989 TI - Nerve ultrasound and 3D-MR neurography suggestive of intraneural perineurioma. PMID- 27001990 TI - Risk factors of postictal generalized EEG suppression in generalized convulsive seizures. PMID- 27001991 TI - Mystery case: Intracranial hemorrhage in adult vein of Galen malformation. PMID- 27001992 TI - Visual cortex hyperexcitability in migraine in response to sound-induced flash illusions. PMID- 27001993 TI - Clinical Reasoning: Stepwise paralysis in a patient with adenocarcinoma of lung. PMID- 27001994 TI - Pearls & Oy-sters: Symptomatic innominate artery disease. PMID- 27001995 TI - Teaching NeuroImages: Severe vasospasm in traumatic brain injury. PMID- 27001996 TI - Identification of Key Items Regarding Personality, Environment, and Life Events to Assess Risk and Resilience Factors for Harmful Alcohol Drinking in Adolescents. AB - AIMS: Alcohol misuse often develops during adolescence involving interacting factors deriving from personality, environment and life events that can be assessed with well-established instruments. However, for specific research purposes, involving the assessment of large data sets, it may be beneficial having a short tool of key items representing the most important risk factors. METHODS: We identified a set of key items from standard questionnaires assessed in about 2000 adolescents. In our longitudinal study we identified important items on personality, environment, and life events explaining alcohol drinking behaviour at the age of 14 years and the increase of alcohol consumption 2 years later. RESULTS: The key items explained 33.4% of variance in alcohol drinking behaviour (vs. 34.8% for original battery) and can be completed in six minutes. CONCLUSIONS: Our item list represents a powerful easy-to-use tool for the examination of alcohol drinking behaviour in adolescents. PMID- 27001997 TI - Occupations associated with COPD risk in the large population-based UK Biobank cohort study. AB - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Exposure to occupational hazards is an important preventable risk factor but the contribution of specific occupations to COPD risk in a general population is uncertain. Our aim was to investigate the association of COPD with occupation in the UK population. METHODS: In 2006-2010, the UK Biobank cohort recruited 502 649 adults aged 40-69 years. COPD cases were identified by prebronchodilator forced expiratory volume in 1 s/forced vital capacity0.05). Hypermethylation at the PPARgamma promoter of plasma DNA correlated with changes in hepatocellular rather than myofibroblast DNA methylation. Similar results were demonstrated in patients with ALD cirrhosis. CONCLUSIONS: Differential DNA methylation at the PPARgamma promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPARgamma could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease. PMID- 27002008 TI - The Impact of Continuous Quality Improvement on a System's Healthcare Costs. PMID- 27002007 TI - Standardized Clinical Pathways for Hospitalized Children and Outcomes. AB - BACKGROUND AND OBJECTIVE: Clinical pathways standardize care for common health conditions. We sought to assess whether institution-wide implementation of multiple standardized pathways was associated with changes in utilization and physical functioning after discharge among pediatric inpatients. METHODS: Interrupted time series analysis of admissions to a tertiary care children's hospital from December 1, 2009 through March 30, 2014. On the basis of diagnosis codes, included admissions were eligible for 1 of 15 clinical pathways implemented during the study period; admissions from both before and after implementation were included. Postdischarge physical functioning improvement was assessed with the Pediatric Quality of Life Inventory 4.0 Generic Core or Infant Scales. Average hospitalization costs, length of stay, readmissions, and physical functioning improvement scores were calculated by month relative to pathway implementation. Segmented linear regression was used to evaluate differences in intercept and trend over time before and after pathway implementation. RESULTS: There were 3808 and 2902 admissions in the pre- and postpathway groups, respectively. Compared with prepathway care, postpathway care was associated with a significant halt in rising costs (prepathway vs postpathway slope difference $155 per month [95% confidence interval -$246 to -$64]; P = .001) and significantly decreased length of stay (prepathway vs post-pathway slope difference -0.03 days per month [95% confidence interval -0.05 to -0.02]; P = .02), without negatively affecting patient physical functioning improvement or readmissions. CONCLUSIONS: Implementation of multiple evidence-based, standardized clinical pathways was associated with decreased resource utilization without negatively affecting patient physical functioning improvement. This approach could be widely implemented to improve the value of care provided. PMID- 27002009 TI - eComment. High-risk multidisciplinary team meetings in thoracic surgery. PMID- 27002011 TI - eComment. Why should aortic valve replacement be performed in asymptomatic patients with an enlarged left ventricle but normal left ventricular function? PMID- 27002010 TI - Serum carbohydrate antigen 12-5 level enhances the prognostic value in primary adenosquamous carcinoma of the lung: a two-institutional experience. AB - OBJECTIVES: Primary adenosquamous carcinoma (ASC) of the lung is rare. The current study was a retrospective two-institutional analysis of surgical therapy with respect to the clinicopathological characteristics and prognostic factors associated with ASC of the lung. METHODS: The clinical records of patients with pathologically confirmed ASC of the lung treated surgically in two centres between January 2008 and December 2014 were retrospectively reviewed. RESULTS: One hundred and four patients with ASC of the lung after surgical intervention, including 68 males and 36 females were identified. The 5-year overall survival (OS) and disease-free survival (DFS) of all ASC stages were 38.3 and 16.9%, respectively. Patients with N0, N1 and N2 ASC [N0 vs N1 (P = 0.047) and N1 vs N2 (P = 0.028), respectively], or Stage I, II and IIIA ASC [Stage I vs Stage II (P = 0.005) and Stage II vs Stage IIIA (P = 0.016), respectively] had significant differences with respect to OS. Multivariate analysis using a Cox proportional hazards model indicated that the level of serum carbohydrate antigen 12-5 (CA 12 5) (normal vs high level, P = 0.029), TNM stage [Stage I vs Stage IIIA (P < 0.001), Stage II vs Stage IIIA (P = 0.001)] and adjuvant chemotherapy (P = 0.027) were significant factors associated with OS in ASC patients, and TNM stage [Stage I vs Stage IIIA (P < 0.001), Stage II vs Stage IIIA (P = 0.003)] and adjuvant chemotherapy (P < 0.001) were the significant prognostic variables for DFS. CONCLUSIONS: Serum CA 12-5 level and TNM status predict the long-term prognosis of resected primary ASC of the lung. Postoperative platinum-based chemotherapy improved survival in patients with ASC. PMID- 27002012 TI - Haemodynamic performance of the small supra-annular Trifecta bioprosthesis: results from a French multicentre study. AB - OBJECTIVES: The St Jude Medical Trifecta bioprosthesis incorporates a single pericardial sheet externally mounted on a titanium stent that provides excellent haemodynamic results. The purpose of this multicentre study was to report on the haemodynamic performance and the expected lower risk of prosthesis-patient mismatch in patient with small aortic annulus diameters. METHODS: The 19- and 21 mm Trifecta valves were implanted in 88 and 266 eligible patients, respectively between 2011 and 2013 at three centres in France (Angers, Rennes and Amiens). The mean age of the population was 78 +/- 7 and 76 +/- 6 years for 19- and 21-mm valve sizes of which 96.6 and 68% were female, respectively. The aortic valve replacement was associated with another surgery in 18.2 and 21.8% in each group, respectively. RESULTS: The mean follow-up was 20.3 +/- 11.9 and 24 +/- 11.4 months for 19- and 21-mm valves, respectively. Early all-cause mortality was 2.5% and late mortality occurred in 5.8% of patients. The mean pressure gradient and the effective orifice area at discharge and at 1 year were respectively 12.4 +/- 4.6 and 14.7 +/- 5.8 mmHg (P = 0.003), 1.5 +/- 0.3 and 1.4 +/- 0.9 cm(2) (P = 0.06) in the 19-mm valve group; 10.4 +/- 3.8 and 11.7 +/- 4.5 mmHg (P = 0.001), 1.8 +/- 0.3 and 1.5 +/- 0.4 cm(2) (P = 0.1) in the 21-mm valve group. At 1 year, only 38 (11%) and 28 (8.1%) patients presented a moderate or severe prosthesis patient mismatch for the two groups. After univariate analysis, no risk factor of mismatch was found. CONCLUSIONS: The 19- and 21-mm St Jude Medical Trifecta provide excellent haemodynamic performance and the rate of moderate and severe prosthesis-patient mismatch is low. PMID- 27002013 TI - eComment. Re: Is cardiac magnetic resonance imaging as accurate as echocardiography in the assessment of aortic valve stenosis? PMID- 27002014 TI - Treatment solution by Omura et al. PMID- 27002015 TI - Treatment solution by Elzain et al. PMID- 27002016 TI - Early transcatheter valve dysfunction after transapical mitral valve-in-valve implantation. AB - Some patients who underwent previous mitral valve surgery experience bioprosthetic valve degeneration or recurrent mitral valve regurgitation, and the transcatheter valve-in-valve or valve-in-ring procedure is a promising therapeutic option. Early thrombotic complications have been recently reported in 0.6-0.8% of TAVI prostheses implanted in aortic position. To the best of our knowledge, this article reports on the first case of thrombotic transcatheter mitral valve dysfunction which occurred on oral anticoagulation with Coumadin in combination with antiplatelet therapy. Although it is quite a rare complication, early thrombotic dysfunction of transcatheter valve prosthesis may occur. PMID- 27002017 TI - Use of the frozen elephant trunk technique in complicated chronic dissection with porcelain aorta and visceral arteries originating from different lumens. AB - A rare case of aortic arch aneurysm combined with chronic aortic dissection is reported. Because the visceral arteries originated from different, equivalently perfused lumens and the descending aorta was circumferentially calcified (porcelain aorta) limiting the possibilities of anastomosing, careful planning of the surgical strategy was of utmost importance. The complex surgery consisted of ascending and total arch replacement using the 'frozen elephant trunk' technique with ThoraflexTM Hybrid Prosthesis (Vascutek, Terumo, Inchinnan, Scotland); however, before insertion of the stent graft, an angioscopic resection of the dissection membrane in the proximal part of the descending aorta was carried out to ensure a complete expansion of the distal edge of the stent within the entire common lumen of the aorta and unimpaired distal flow in both lumens below the stent graft. The surgery and the postoperative course were uneventful. PMID- 27002018 TI - eComment. Re: Use of the frozen elephant trunk technique in complicated chronic dissection with porcelain aorta and visceral arteries originating from different lumens. PMID- 27002019 TI - eComment. Images of aortic dissection while on extracorporeal membrane oxygenation. PMID- 27002020 TI - Management of a patient with giant aneurysms in the popliteal and coronary arteries. AB - Coexistence of multiple peripheric arterial and coronary artery aneurysms of different sizes is extremely rare in young adults. We present a case of rare giant coronary aneurysm and concurrent giant left popliteal aneurysm treated with classical open repair. PMID- 27002021 TI - eComment: The value of the correct diagnosis is not inferior to the efficiency of the appropriate treatment. PMID- 27002023 TI - Three-Dimensional Visualization of the Tubular-Lamellar Transformation of the Internal Plastid Membrane Network during Runner Bean Chloroplast Biogenesis. AB - Chloroplast biogenesis is a complex process that is integrated with plant development, leading to fully differentiated and functionally mature plastids. In this work, we used electron tomography and confocal microscopy to reconstruct the process of structural membrane transformation during the etioplast-to-chloroplast transition in runner bean (Phaseolus coccineus). During chloroplast development, the regular tubular network of paracrystalline prolamellar bodies (PLBs) and the flattened porous membranes of prothylakoids develop into the chloroplast thylakoids. Three-dimensional reconstruction is required to provide us with a more complete understanding of this transformation. We provide spatial models of the bean chloroplast biogenesis that allow such reconstruction of the internal membranes of the developing chloroplast and visualize the transformation from the tubular arrangement to the linear system of parallel lamellae. We prove that the tubular structure of the PLB transforms directly to flat slats, without dispersion to vesicles. We demonstrate that the grana/stroma thylakoid connections have a helical character starting from the early stages of appressed membrane formation. Moreover, we point out the importance of particular chlorophyll-protein complex components in the membrane stacking during the biogenesis. The main stages of chloroplast internal membrane biogenesis are presented in a movie that shows the time development of the chloroplast biogenesis as a dynamic model of this process. PMID- 27002024 TI - 3D Visualization of Thylakoid Membrane Development. PMID- 27002025 TI - S-type Anion Channels SLAC1 and SLAH3 Function as Essential Negative Regulators of Inward K+ Channels and Stomatal Opening in Arabidopsis. AB - Drought stress induces stomatal closure and inhibits stomatal opening simultaneously. However, the underlying molecular mechanism is still largely unknown. Here we show that S-type anion channels SLAC1 and SLAH3 mainly inhibit inward K+ (K+in) channel KAT1 by protein-protein interaction, and consequently prevent stomatal opening in Arabidopsis. Voltage-clamp results demonstrated that SLAC1 inhibited KAT1 dramatically, but did not inhibit KAT2. SLAH3 inhibited KAT1 to a weaker degree relative to SLAC1. Both the N terminus and the C terminuses of SLAC1 inhibited KAT1, but the inhibition by the N terminus was stronger. The C terminus was essential for the inhibition of KAT1 by SLAC1. Furthermore, drought stress strongly up-regulated the expression of SLAC1 and SLAH3 in Arabidopsis guard cells, and the over-expression of wild type and truncated SLAC1 dramatically impaired K+in currents of guard cells and light-induced stomatal opening. Additionally, the inhibition of KAT1 by SLAC1 and KC1 only partially overlapped, suggesting that SLAC1 and KC1 inhibited K+in channels using different molecular mechanisms. Taken together, we discovered a novel regulatory mechanism for stomatal movement, in which singling pathways for stomatal closure and opening are directly coupled together by protein-protein interaction between SLAC1/SLAH3 and KAT1 in Arabidopsis. PMID- 27002059 TI - Very Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiological Changes in Responders and Nonresponders. AB - OBJECTIVE: Type 2 diabetes mellitus (T2DM) is generally regarded as an irreversible chronic condition. Because a very low-calorie diet (VLCD) can bring about acute return to normal glucose control in some people with T2DM, this study tested the potential durability of this normalization. The underlying mechanisms were defined. RESEARCH DESIGN AND METHODS: People with a T2DM duration of 0.5-23 years (n = 30) followed a VLCD for 8 weeks. All oral agents or insulins were stopped at baseline. Following a stepped return to isocaloric diet, a structured, individualized program of weight maintenance was provided. Glucose control, insulin sensitivity, insulin secretion, and hepatic and pancreas fat content were quantified at baseline, after return to isocaloric diet, and after 6 months to permit the primary comparison of change between post-weight loss and 6 months in responders. Responders were defined as achieving fasting blood glucose <7 mmol/L after return to isocaloric diet. RESULTS: Weight fell (98.0 +/- 2.6 to 83.8 +/- 2.4 kg) and remained stable over 6 months (84.7 +/- 2.5 kg). Twelve of 30 participants achieved fasting plasma glucose <7 mmol/L after return to isocaloric diet (responders), and 13 of 30 after 6 months. Responders had a shorter duration of diabetes and a higher initial fasting plasma insulin level. HbA1c fell from 7.1 +/- 0.3 to 5.8 +/- 0.2% (55 +/- 4 to 40 +/- 2 mmol/mol) in responders (P < 0.001) and from 8.4 +/- 0.3 to 8.0 +/- 0.5% (68 +/- 3 to 64 +/- 5 mmol/mol) in nonresponders, remaining constant at 6 months (5.9 +/- 0.2 and 7.8 +/- 0.3% [41 +/- 2 and 62 +/- 3 mmol/mol], respectively). The responders were characterized by return of first-phase insulin response. CONCLUSIONS: A robust and sustainable weight loss program achieved continuing remission of diabetes for at least 6 months in the 40% who responded to a VLCD by achieving fasting plasma glucose of <7 mmol/L. T2DM is a potentially reversible condition. PMID- 27002061 TI - Evidence for a Role for NAD(P)H Dehydrogenase in Concentration of CO2 in the Bundle Sheath Cell of Zea mays. AB - Prior studies with Nicotiana and Arabidopsis described failed assembly of the chloroplastic NDH [NAD(P)H dehydrogenase] supercomplex by serial mutation of several subunit genes. We examined the properties of Zea mays leaves containing Mu and Ds insertions into nuclear gene exons encoding the critical o- and n subunits of NDH, respectively. In vivo reduction of plastoquinone in the dark was sharply diminished in maize homozygous mutant compared to normal leaves but not to the extreme degree observed for the corresponding lesions in Arabidopsis. The net carbon assimilation rate (A) at high irradiance and saturating CO2 levels was reduced by one-half due to NDH mutation in maize although no genotypic effect was evident at very low CO2 levels. Simultaneous assessment of chlorophyll fluorescence and A in maize at low (2% by volume) and high (21%) O2 levels indicated the presence of a small, yet detectable, O2-dependent component of total linear photosynthetic electron transport in 21% O2 This O2-dependent component decreased with increasing CO2 level indicative of photorespiration. Photorespiration was generally elevated in maize mutant compared to normal leaves. Quantification of the proportion of total electron transport supporting photorespiration enabled estimation of the bundle sheath cell CO2 concentration (Cb) using a simple kinetic model of ribulose bisphosphate carboxylase/oxygenase function. The A versus Cb relationships overlapped for normal and mutant lines consistent with occurrence of strictly CO2-limited photosynthesis in the mutant bundle sheath cell. The results are discussed in terms of a previously reported CO2 concentration model [Laisk A, Edwards GE (2000) Photosynth Res 66: 199-224]. PMID- 27002062 TI - Effect of Rifampin on the Disposition of Brivaracetam in Human Subjects: Further Insights into Brivaracetam Hydrolysis. AB - Brivaracetam (BRV) is a high-affinity synaptic vesicle protein 2A ligand developed for the treatment of uncontrolled partial-onset seizures. The present phase I, open-label, two-way crossover study was designed to assess the effect of rifampin on the pharmacokinetics of BRV and its hydroxy (BRV-OH), acid (BRV-AC), and hydroxy acid (BRV-OHAC) metabolites. Twenty-six healthy subjects received BRV (150-mg single oral dose) either alone or following 5 days of rifampin 600 mg/day. BRV and its metabolites were examined for their plasma profiles and urinary excretion. Pharmacokinetic modeling was developed to estimate the rate constants of the various metabolic routes. Parallel in vitro assays were conducted to characterize the hydrolysis of BRV to BRV-AC as well as to identify any potential effect of rifampin on the hydrolysis reaction. Rifampin did not significantly affect the maximum plasma concentration (Cmax) of BRV, but decreased its area under the curve (AUC) by 45%. In addition, rifampin significantly increased the AUC of BRV-OH (+109%), decreased the AUC of BRV-AC ( 53%), but had little effect on BRV-OHAC (-10%). In vitro assays showed that the major urinary metabolite BRV-AC (33% of the dose) was likely to be formed by amidase EC 3.5.1.4. In vitro data indicated that the enzyme was not significantly inhibited nor induced by rifampin. Modeling confirmed that all of the observed changes in vivo were secondary to the induction of the CYP2C19-mediated hydroxylation of BRV to BRV-OH (3.7-fold increase in the rate constant). PMID- 27002060 TI - Comparative Transcriptomic Approaches Exploring Contamination Stress Tolerance in Salix sp. Reveal the Importance for a Metaorganismal de Novo Assembly Approach for Nonmodel Plants. AB - Metatranscriptomic study of nonmodel organisms requires strategies that retain the highly resolved genetic information generated from model organisms while allowing for identification of the unexpected. A real-world biological application of phytoremediation, the field growth of 10 Salix cultivars on polluted soils, was used as an exemplar nonmodel and multifaceted crop response well-disposed to the study of gene expression. Sequence reads were assembled de novo to create 10 independent transcriptomes, a global transcriptome, and were mapped against the Salix purpurea 94006 reference genome. Annotation of assembled contigs was performed without a priori assumption of the originating organism. Global transcriptome construction from 3.03 billion paired-end reads revealed 606,880 unique contigs annotated from 1588 species, often common in all 10 cultivars. Comparisons between transcriptomic and metatranscriptomic methodologies provide clear evidence that nonnative RNA can mistakenly map to reference genomes, especially to conserved regions of common housekeeping genes, such as actin, alpha/beta-tubulin, and elongation factor 1-alpha. In Salix, Rubisco activase transcripts were down-regulated in contaminated trees across all 10 cultivars, whereas thiamine thizole synthase and CP12, a Calvin Cycle master regulator, were uniformly up-regulated. De novo assembly approaches, with unconstrained annotation, can improve data quality; care should be taken when exploring such plant genetics to reduce de facto data exclusion by mapping to a single reference genome alone. Salix gene expression patterns strongly suggest cultivar-wide alteration of specific photosynthetic apparatus and protection of the antenna complexes from oxidation damage in contaminated trees, providing an insight into common stress tolerance strategies in a real-world phytoremediation system. PMID- 27002063 TI - Understanding dislocation mechanics at the mesoscale using phase field dislocation dynamics. AB - In this paper, we discuss the formulation, recent developments and findings obtained from a mesoscale mechanics technique called phase field dislocation dynamics (PFDD). We begin by presenting recent advancements made in modelling face-centred cubic materials, such as integration with atomic-scale simulations to account for partial dislocations. We discuss calculations that help in understanding grain size effects on transitions from full to partial dislocation mediated slip behaviour and deformation twinning. Finally, we present recent extensions of the PFDD framework to alternative crystal structures, such as body centred cubic metals, and two-phase materials, including free surfaces, voids and bi-metallic crystals. With several examples we demonstrate that the PFDD model is a powerful and versatile method that can bridge the length and time scales between atomistic and continuum-scale methods, providing a much needed understanding of deformation mechanisms in the mesoscale regime. PMID- 27002064 TI - A structured continuum modelling framework for martensitic transformation and reorientation in shape memory materials. AB - Models for shape memory material behaviour can be posed in the framework of a structured continuum theory. We study such a framework in which a scalar phase fraction field and a tensor field of martensite reorientation describe the material microstructure, in the context of finite strains. Gradients of the microstructural descriptors naturally enter the formulation and offer the possibility to describe and resolve phase transformation localizations. The constitutive theory is thoroughly described by a single free energy function in conjunction with a path-dependent dissipation function. Balance laws in the form of differential equations are obtained and contain both bulk and surface terms, the latter in terms of microstreses. A natural constraint on the tensor field for martensite reorientation gives rise to reactive fields in these balance laws. Conditions ensuring objectivity as well as the relation of this framework to that provided by currently used models for shape memory alloy behaviour are discussed. PMID- 27002065 TI - Some variance reduction methods for numerical stochastic homogenization. AB - We give an overview of a series of recent studies devoted to variance reduction techniques for numerical stochastic homogenization. Numerical homogenization requires that a set of problems is solved at the microscale, the so-called corrector problems. In a random environment, these problems are stochastic and therefore need to be repeatedly solved, for several configurations of the medium considered. An empirical average over all configurations is then performed using the Monte Carlo approach, so as to approximate the effective coefficients necessary to determine the macroscopic behaviour. Variance severely affects the accuracy and the cost of such computations. Variance reduction approaches, borrowed from other contexts in the engineering sciences, can be useful. Some of these variance reduction techniques are presented, studied and tested here. PMID- 27002066 TI - Existence, numerical convergence and evolutionary relaxation for a rate independent phase-transformation model. AB - We revisit the model for a two-well phase transformation in a linearly elastic body that was introduced and studied in Mielke et al. (2002 Arch. Ration. Mech. Anal. 162: , 137-177). This energetic rate-independent system is posed in terms of the elastic displacement and an internal variable that gives the phase portion of the second phase. We use a new approach based on mutual recovery sequences, which are adjusted to a suitable energy increment plus the associated dissipated energy and, thus, enable us to pass to the limit in the construction of energetic solutions. We give three distinct constructions of mutual recovery sequences which allow us (i) to generalize the existence result in Mielke et al. (2002), (ii) to establish the convergence of suitable numerical approximations via space time discretization and (iii) to perform the evolutionary relaxation from the pure-state model to the relaxed-mixture model. All these results rely on weak converge and involve the H-measure as an essential tool. PMID- 27002067 TI - Capillary-induced deformations of a thin elastic sheet. AB - We develop a three-dimensional model for capillary origami systems in which a rectangular plate has finite thickness, is allowed to stretch and undergoes small deflections. This latter constraint limits our description of the encapsulation process to its initial folding phase. We first simplify the resulting system of equations to two dimensions by assuming that the plate has infinite aspect ratio, which allows us to compare our approach to known two-dimensional capillary origami models for inextensible plates. Moreover, as this two-dimensional model is exactly solvable, we give an expression for its solution in terms of its parameters. We then turn to the full three-dimensional model in the limit of small drop volume and provide numerical simulations showing how the plate and the drop deform due to the effect of capillary forces. PMID- 27002068 TI - Length scales and pinning of interfaces. AB - The pinning of interfaces and free discontinuities by defects and heterogeneities plays an important role in a variety of phenomena, including grain growth, martensitic phase transitions, ferroelectricity, dislocations and fracture. We explore the role of length scale on the pinning of interfaces and show that the width of the interface relative to the length scale of the heterogeneity can have a profound effect on the pinning behaviour, and ultimately on hysteresis. When the heterogeneity is large, the pinning is strong and can lead to stick-slip behaviour as predicted by various models in the literature. However, when the heterogeneity is small, we find that the interface may not be pinned in a significant manner. This shows that a potential route to making materials with low hysteresis is to introduce heterogeneities at a length scale that is small compared with the width of the phase boundary. Finally, the intermediate setting where the length scale of the heterogeneity is comparable to that of the interface width is characterized by complex interactions, thereby giving rise to a non-monotone relationship between the relative heterogeneity size and the critical depinning stress. PMID- 27002069 TI - Phase-field modelling of ductile fracture: a variational gradient-extended plasticity-damage theory and its micromorphic regularization. AB - This work outlines a novel variational-based theory for the phase-field modelling of ductile fracture in elastic-plastic solids undergoing large strains. The phase field approach regularizes sharp crack surfaces within a pure continuum setting by a specific gradient damage modelling. It is linked to a formulation of gradient plasticity at finite strains. The framework includes two independent length scales which regularize both the plastic response as well as the crack discontinuities. This ensures that the damage zones of ductile fracture are inside of plastic zones, and guarantees on the computational side a mesh objectivity in post-critical ranges. PMID- 27002070 TI - Discrete structures in continuum descriptions of defective crystals. AB - I discuss various mathematical constructions that combine together to provide a natural setting for discrete and continuum geometric models of defective crystals. In particular, I provide a quite general list of 'plastic strain variables', which quantifies inelastic behaviour, and exhibit rigorous connections between discrete and continuous mathematical structures associated with crystalline materials that have a correspondingly general constitutive specification. PMID- 27002071 TI - Continuum mechanics, stresses, currents and electrodynamics. AB - The Eulerian approach to continuum mechanics does not make use of a body manifold. Rather, all fields considered are defined on the space, or the space time, manifolds. Sections of some vector bundle represent generalized velocities which need not be associated with the motion of material points. Using the theories of de Rham currents and generalized sections of vector bundles, we formulate a weak theory of forces and stresses represented by vector-valued currents. Considering generalized velocities represented by differential forms and interpreting such a form as a generalized potential field, we present a weak formulation of pre-metric, p-form electrodynamics as a natural example of the foregoing theory. Finally, it is shown that the assumptions leading to p-form electrodynamics may be replaced by the condition that the force functional is continuous with respect to the flat topology of forms. PMID- 27002072 TI - Zig-zag twins and helical phase transformations. AB - We demonstrate the large bending deformation induced by an array of permanent magnets (applied field ~0.02 T) designed to minimize poles in the bent state of the crystal. Planar cantilevers of NiMnGa (5M modulated martensite) ferromagnetic shape memory alloy deform into an arched shape according to theory, with a zig zag microstructure that complies with the kinematic and magnetic compatibility between adjacent twin variants. A general theory of bent and twisted states is given, applicable to both twinning and austenite/martensite transformations. Some of these configurations achieve order-of-magnitude amplification of rotation and axial strain. We investigate also atomistic analogues of these bent and twisted configurations with perfect interfaces between phases. These mechanisms of large deformation, induced by small magnetic fields or temperature changes, have potential application to the development of new actuation technologies for micro robotic systems. PMID- 27002073 TI - Trends and challenges in the mechanics of complex materials: a view. AB - This article introduces the collection of papers in this issue of the Philosophical Transactions of the Royal Society A and offers a perspective view on the description of the mechanics of material characterized by a prominent influence of small-scale phenomena on the gross mechanical behaviour. PMID- 27002074 TI - A long-acting formulation of the integrase inhibitor raltegravir protects humanized BLT mice from repeated high-dose vaginal HIV challenges. AB - OBJECTIVES: Pre-exposure prophylaxis (PrEP) using antiretroviral drugs (ARVs) has been shown to reduce HIV transmission in people at high risk of HIV infection. Adherence to PrEP strongly correlates with the level of HIV protection. Long acting injectable ARVs provide sustained systemic drug exposures over many weeks and can improve adherence due to infrequent parenteral administration. Here, we evaluated a new long-acting formulation of raltegravir for prevention of vaginal HIV transmission. METHODS: Long-acting raltegravir was administered subcutaneously to BALB/c, NSG (NOD-scid-gamma) and humanized BLT (bone marrow liver-thymus) mice and rhesus macaques. Raltegravir concentration in peripheral blood and tissue was analysed. Suppression of HIV replication was assessed in infected BLT mice. Two high-dose HIV vaginal challenges were used to evaluate protection from HIV transmission in BLT mice. RESULTS: Two weeks after a single subcutaneous injection of long-acting raltegravir in BLT mice (7.5 mg) and rhesus macaques (160 mg), the plasma concentration of raltegravir was comparable to 400 mg orally, twice daily in humans. Serum collected from mice 3 weeks post administration of long-acting raltegravir efficiently blocked HIV infection of TZM-bl indicator cells in vitro. Administration of long-acting raltegravir suppressed viral RNA in plasma and cervico-vaginal fluids of infected BLT mice, demonstrating penetration of active raltegravir into the female reproductive tract. Using transmitted/founder HIV we observed that BLT mice administered a single subcutaneous dose of long-acting raltegravir were protected from two high dose HIV vaginal challenges 1 week and 4 weeks after drug administration. CONCLUSIONS: These preclinical results demonstrated the efficacy of long-acting raltegravir in preventing vaginal HIV transmission. PMID- 27002075 TI - Is the problem list in the eye of the beholder? An exploration of consistency across physicians. AB - OBJECTIVE: Quantify the variability of patients' problem lists - in terms of the number, type, and ordering of problems - across multiple physicians and assess physicians' criteria for organizing and ranking diagnoses. MATERIALS AND METHODS: In an experimental setting, 32 primary care physicians generated and ordered problem lists for three identical complex internal medicine cases expressed as detailed 2- to 4-page abstracts and subsequently expressed their criteria for ordering items in the list. We studied variability in problem list length. We modified a previously validated rank-based similarity measure, with range of zero to one, to quantify agreement between pairs of lists and calculate a single consensus problem list that maximizes agreement with each physician. Physicians' reasoning for the ordering of the problem lists was recorded. RESULTS: Subjects' problem lists were highly variable. The median problem list length was 8 (range: 3-14) for Case A, 10 (range: 4-20) for Case B, and 7 (range: 3-13) for Case C. The median indices of agreement - taking into account the length, content, and order of lists - over all possible physician pairings was 0.479, 0.371, 0.509, for Cases A, B, and C, respectively. The median agreements between the physicians' lists and the consensus list for each case were 0.683, 0.581, and 0.697 (for Cases A, B, and C, respectively).Out of a possible 1488 pairings, 2 lists were identical. Physicians most frequently ranked problem list items based on their acuity and immediate threat to health. CONCLUSIONS: The problem list is a physician's mental model of a patient's health status. These mental models were found to vary significantly between physicians, raising questions about whether problem lists created by individual physicians can serve their intended purpose to improve care coordination. PMID- 27002076 TI - The frequency of inappropriate nonformulary medication alert overrides in the inpatient setting. AB - BACKGROUND: Experts suggest that formulary alerts at the time of medication order entry are the most effective form of clinical decision support to automate formulary management. OBJECTIVE: Our objectives were to quantify the frequency of inappropriate nonformulary medication (NFM) alert overrides in the inpatient setting and provide insight on how the design of formulary alerts could be improved. METHODS: Alert overrides of the top 11 (n = 206) most-utilized and highest-costing NFMs, from January 1 to December 31, 2012, were randomly selected for appropriateness evaluation. Using an empirically developed appropriateness algorithm, appropriateness of NFM alert overrides was assessed by 2 pharmacists via chart review. Appropriateness agreement of overrides was assessed with a Cohen's kappa. We also assessed which types of NFMs were most likely to be inappropriately overridden, the override reasons that were disproportionately provided in the inappropriate overrides, and the specific reasons the overrides were considered inappropriate. RESULTS: Approximately 17.2% (n = 35.4/206) of NFM alerts were inappropriately overridden. Non-oral NFM alerts were more likely to be inappropriately overridden compared to orals. Alerts overridden with "blank" reasons were more likely to be inappropriate. The failure to first try a formulary alternative was the most common reason for alerts being overridden inappropriately. CONCLUSION: Approximately 1 in 5 NFM alert overrides are overridden inappropriately. Future research should evaluate the impact of mandating a valid override reason and adding a list of formulary alternatives to each NFM alert; we speculate these NFM alert features may decrease the frequency of inappropriate overrides. PMID- 27002077 TI - Lifestyle factors and health-related quality of life in bladder cancer survivors: a systematic review. AB - PURPOSE: Diet, physical activity, and smoking cessation are modifiable lifestyle factors that have been shown to improve health-related quality of life (HRQOL) in many cancer survivors. Our objective was to systematically review the literature on the associations between lifestyle factors, namely diet, physical activity, smoking status, and HRQOL in bladder cancer survivors. METHODS: We queried PubMed, EMBASE, and Cochrane libraries. Two reviewers reviewed abstracts independently, and a third reviewer arbitrated disagreements. A descriptive analysis was performed. Quality assessment was conducted using the Newcastle Ottawa Quality Assessment Scale for observational studies and the Cochrane Risk of Bias Tool for clinical trials. RESULTS: We identified 1167 publications in the initial search, of which 9 met inclusion criteria for full-text review. We were able to obtain data on the outcomes of interest for 5 publications. A total of 1288 patients who underwent treatment for bladder cancer were included. Three studies were observational by design and two were randomized controlled trials. Physical activity was addressed by 4 studies, smoking status by 2 studies, and diet by 1 study. CONCLUSIONS: The review highlights the limited evidence around lifestyle factors and quality of life in bladder cancer survivors. There is some evidence for a positive association between HRQOL and physical activity, but insufficient evidence upon which to draw conclusions about the effects of consuming fruits and vegetables or non-smoking. IMPLICATIONS FOR CANCER SURVIVORS: There is limited evidence to support a positive association between health-related quality of life and physical activity, but insufficient evidence upon which to base any conclusions about consumption of fruits and vegetables or smoking cessation in bladder cancer survivors. PMID- 27002078 TI - NK Cells in HIV Disease. AB - Natural killer (NK) cells play a critical role in viral immunity. In the setting of HIV infection, epidemiologic and functional evidence support a role for NK cells in both protection from new infection and in viral control. Specifically, NK cells directly mediate immune pressure leading to virus evolution, and NK cell receptor genotypic profiles, clonal repertoires, and functional capacity have all been implicated in virus containment. In addition, indirect NK cell-mediated antibody-dependent cellular cytotoxicity has been linked to vaccine-induced protective immunity against HIV infection. With recent advances in our understanding of NK cell deficiency, development, memory-like responses, and editing of the adaptive immune system, the opportunities to direct and exploit NK cell antiviral immunity to target HIV have exponentially grown. In this review, we seek to highlight the intersections between discoveries in basic NK cell biology and the challenges of HIV chronic infection, vaccine development, and cure/eradication strategies. PMID- 27002080 TI - Geography as Disparity: The Shifting Burden of Heart Disease. PMID- 27002082 TI - Impact of Socioeconomic Status, Ethnicity, and Urbanization on Risk Factor Profiles of Cardiovascular Disease in Africa. AB - Africa is a continent characterized by marked ethnic, sociodemographic, and economic diversity, with profound changes in many regions over the past 2 decades. This diversity has an impact on cardiovascular disease presentation and outcomes. Within Africa and within the individual countries, one can find regions having predominantly communicable diseases such as rheumatic heart disease, tuberculous pericarditis, or cardiomyopathy and others having a marked increase in noncommunicable disease such as hypertension and hypertensive heart disease. Ischemic heart disease remains rare in most countries. Difficulties in the planning and implementation of effective health care in most African countries are compounded by a paucity of studies and a low rate of investment in research and data acquisition. The fiduciary responsibilities of companies working in Africa should include the effective and efficient use of natural resources to promote the overall health of populations. PMID- 27002081 TI - Changes in the Geographic Patterns of Heart Disease Mortality in the United States: 1973 to 2010. AB - BACKGROUND: Although many studies have documented the dramatic declines in heart disease mortality in the United States at the national level, little attention has been given to the temporal changes in the geographic patterns of heart disease mortality. METHODS AND RESULTS: Age-adjusted and spatially smoothed county-level heart disease death rates were calculated for 2-year intervals from 1973 to 1974 to 2009 to 2010 for those aged >=35 years. Heart disease deaths were defined according to the International Classification of Diseases codes for diseases of the heart in the eighth, ninth, and tenth revisions of the International Classification of Diseases. A fully Bayesian spatiotemporal model was used to produce precise rate estimates, even in counties with small populations. A substantial shift in the concentration of high-rate counties from the Northeast to the Deep South was observed, along with a concentration of slow decline counties in the South and a nearly 2-fold increase in the geographic inequality among counties. CONCLUSIONS: The dramatic change in the geographic patterns of heart disease mortality during 40 years highlights the importance of small-area surveillance to reveal patterns that are hidden at the national level, gives communities the historical context for understanding their current burden of heart disease, and provides important clues for understanding the determinants of the geographic disparities in heart disease mortality. PMID- 27002083 TI - Absent at Birth: An Unusual Case of Deep Vein Thrombosis. PMID- 27002084 TI - ECG Response: March 22, 2016. PMID- 27002079 TI - Managing Migraine During Pregnancy and Lactation. AB - While over half of women with migraine report improvement during pregnancy, having a history of migraine may increase the chance of negative health outcomes. The state of pregnancy increases the risk of several dangerous secondary headache disorders, especially those associated with hypertensive disorders of pregnancy, and providers need to know the red flags to diagnose and treat emergently. Non pharmacological migraine treatments can be instituted in advance of pregnancy as many are considered the safest options during pregnancy, but understanding the safety of medications and dietary supplements ensures appropriate care for the refractory migraine patient. New controversy exists over the safety of several historically routine and safe migraine treatment options in pregnancy, such as magnesium, acetaminophen, ondansetron, and butalbital. While it is not clear if breastfeeding decreases the postpartum recurrence of migraine, understanding safe treatment options during lactation can allow women to continue breastfeeding while achieving migraine relief. PMID- 27002085 TI - Giant Pulmonary Artery Aneurysm in a Patient With Marfan Syndrome and Pulmonary Hypertension. PMID- 27002086 TI - Mending a Darkened Heart: Alkaptonuria Discovered During Aortic Valve Replacement. PMID- 27002087 TI - Letter by Daniels and Burns Regarding Article, "Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A Decade in Review". PMID- 27002088 TI - Response to Letter Regarding Article, "Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A Decade in Review". PMID- 27002089 TI - Letter by Aquaro et al Regarding Article, "Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis". PMID- 27002090 TI - Letter by Cohen and Maurer Regarding Article, "Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis". PMID- 27002092 TI - Letter by Kuller and Neaton Regarding Article, "Association of Race With Mortality and Cardiovascular Events in a Large Cohort of US Veterans". PMID- 27002093 TI - Response to Letter Regarding Article, "Association of Race With Mortality and Cardiovascular Events in a Large Cohort of US Veterans". PMID- 27002091 TI - Response to Letters Regarding Article, "Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis". PMID- 27002095 TI - Intracardiac fistula in a child: a rare complication of infective endocarditis. PMID- 27002094 TI - Relative Risk Factors for Cardiac Erosion Following Transcatheter Closure of Atrial Septal Defects: A Case-Control Study. AB - BACKGROUND: Transcatheter closure of secundum atrial septal defects (ASD) using the Amplatzer septal occluder is generally safe and effective, but erosion into the pericardial space or aorta has been described. Although the absolute risk of this complication is low, there has been no assessment of relative risk factors. METHODS AND RESULTS: All erosions reported to St. Jude Medical after ASD closure with an Amplatzer septal occluder (cases) were compared with controls (matched 2:1) who underwent ASD closure but did not develop an erosion. A total of 125 erosions were reported between 2002 and 2014, including 95 with an available echocardiogram. The median duration from implant to erosion was 14 days, but was >1 year in 16 patients. Nine patients (all age >=17 years) who died were more likely to have an oversized device, and to have erosion into the aorta, than survivors. Aortic or superior vena cava rim deficiencies were more common in cases than in controls. In addition, larger balloon-sized ASD diameter, Amplatzer septal occluder device size, and device size-ASD diameter difference, and smaller weight:device size ratio were associated with erosion. On multivariable analysis, deficiency of any rim, device >5 mm larger than ASD diameter, and weight:device size ratio were associated with erosion. CONCLUSIONS: In addition to aortic rim deficiency, which was almost universal among erosion cases, there were several relative risk factors for erosion after ASD closure with the Amplatzer septal occluder device. To understand the mechanisms of and absolute risk factors for this uncommon but serious complication, an adequately powered prospective study with thorough echocardiographic evaluation will be critical. PMID- 27002096 TI - Acute aortic regurgitation due to rupture of an anomalous cord from the raphe. PMID- 27002097 TI - About thymic carcinomas: challenges in diagnosis and management. AB - BACKGROUND: Thymic carcinomas are rare tumors with a challenging diagnosis. Our aim was to report our 17-year experience of these tumors and to highlight the challenges encountered and the main differential diagnoses ruled out. METHODS: We studied 12 (92%) men and 1 (7.7%) woman with a mean age of 37 years (range 15-60 years). All patients were symptomatic, with chest pain representing the most frequent symptom. Radiology revealed anterior mediastinal masses in all cases, with either infiltration of the adjacent organs or pulmonary parenchymal metastases. RESULTS: The diagnosis was made on surgical biopsies in 12 cases and a lymph node biopsy in one. Microscopic examination revealed squamous carcinoma in 3 cases, synovial sarcoma in 1, mucinous adenocarcinoma in 1, undifferentiated carcinoma in 2, clear cell carcinoma in 1, lymphoepithelioma-like carcinoma in 2, atypical carcinoid tumor in 2, and sarcomatoid carcinoma in 1. Total surgical resection was possible in one patient after neoadjuvant chemotherapy and radiotherapy. Follow-up was possible in only 6 patients, and the mean survival reached 13 months. CONCLUSION: In spite of the lack of follow-up information, this study demonstrates the poor outcome associated with these tumors and the need for standardized treatment. PMID- 27002098 TI - Procalcitonin level for prediction of postoperative infection in cardiac surgery. AB - BACKGROUND: Diagnosing infection after cardiac surgery remains difficult due to the systemic inflammatory response induced by cardiopulmonary bypass. We compared procalcitonin levels with white blood cell counts as predictors of infection after cardiac surgery. METHODS: We prospectively enrolled 100 consecutive adult cardiac patients. Postoperative white blood cell counts, serum procalcitonin levels, and blood cultures were examined. RESULT: The sensitivity and specificity of white blood cell count and procalcitonin > 2 ng mL(-1) were 60% and 100%, 58.8% and 42.5%, respectively. Procalcitonin > 7 ng mL(-1) had 95% sensitivity and 80% specificity. Receiver-operating characteristic analysis showed a greater area under the curve for procalcitonin level (p < 0.0001) compared to white blood cell count (p = 0.31). Patients with positive blood cultures had significantly higher procalcitonin levels (51.97 +/- 39.62 vs. 6.67 +/- 10.73 ng mL(-1)), Acute Physiology and Chronic Health Evaluation-II scores (16.95 +/- 3.24 vs. 13.60 +/- 2.98), and intensive care unit stay (6.35 +/- 3.42 vs. 4.6 +/- 2.2 days). Non survivors had significantly higher Acute Physiology and Chronic Health Evaluation II scores (19.09 +/- 1.30 vs. 13.67 +/- 2.97) and procalcitonin levels (43.83 +/- 52.15 vs. 12.26 +/- 19.89 ng mL(-1)) but on logistic regression analysis, only Acute Physiology and Chronic Health Evaluation-II score was an independent risk factor for mortality. CONCLUSION: The diagnostic accuracy of procalcitonin for bacterial infection is fairly high. Acute Physiology and Chronic Health Evaluation-II score is a better predictor of mortality and morbidity than absolute procalcitonin level. Procalcitonin > 7 ng mL(-1) can prognosticate and identify the high-risk group. PMID- 27002099 TI - Type A aortic dissection model to improve endovascular research and technologies. AB - OBJECTIVE: Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment. METHODS: Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models. RESULTS: Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.9 +/- 1.4 cm proximally from the aortic annulus, with a length of 4.6 +/- 0.9 cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.63 +/- 0.163 cm in the ascending aorta. After stent implantation, this distance decreased to 0.26 +/- 0.12 cm. CONCLUSION: This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons. PMID- 27002100 TI - Genetic polymorphism in postoperative sepsis after open heart surgery in infants. AB - BACKGROUND: Sepsis is one of the complications following open heart surgery. Toll like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. METHODS: A prospective cohort study was conducted in 108 children <1-year old who underwent open heart surgery with a Basic Aristotle score >=6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. RESULTS: Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. CONCLUSIONS: Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants <1-year old undergoing complex open heart surgery. PMID- 27002101 TI - The Association Between Serum Procalcitonin Levels and Severity of Coronary Artery Disease Assessed by SYNTAX Score in Patients With Acute Coronary Syndrome. AB - The SYNTAX score (SX score) is a useful score for assessing the severity of coronary artery disease (CAD). Previous studies have demonstrated a close relationship between SX score and inflammation. Procalcitonin (PCT) is an early inflammatory marker, especially during sepsis. Thus, in this study, we aimed to investigate the relationship between SX score and serum PCT levels. A total of 545 patients were enrolled in this prospective cross-sectional study and were divided into 2 subgroups, according to their SX score. Serum PCT and high sensitivity C-reactive protein levels were measured. Serum PCT levels were higher in the high SX score group compared to the low-intermediate SX score group (P < .001). Serum PCT levels were an independent predictor of a high SX score in patients with acute coronary syndrome (P = .001). As patients with a higher SX score had increased serum PCT levels on admission, serum PCT may be useful for identifying patients with severe CAD. PMID- 27002102 TI - Hamstring and Quadriceps Isokinetic Strength Deficits Are Weak Risk Factors for Hamstring Strain Injuries: A 4-Year Cohort Study. AB - BACKGROUND: A hamstring strain injury (HSI) has become the most common noncontact injury in soccer. Isokinetic muscle strength deficits are considered a risk factor for HSIs. However, underpowered studies with small sample sizes unable to determine small associations have led to inconclusive results regarding the role of isokinetic strength and strength testing in HSIs. PURPOSE: To examine whether differences in isokinetic strength measures of knee flexion and extension represent risk factors for hamstring injuries in a large cohort of professional soccer players in an adequately powered study design. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 614 professional soccer players from 14 teams underwent isokinetic strength testing during preseason screening. Testing consisted of concentric knee flexion and extension at 60 deg/s and 300 deg/s and eccentric knee extension at 60 deg/s. A clustered multiple logistic regression analysis was used to identify variables associated with the risk of HSIs. Receiver operating characteristic (ROC) curves were calculated to determine sensitivity and specificity. RESULTS: Of the 614 players, 190 suffered an HSI during the 4 seasons. Quadriceps concentric strength at 60 deg/s (odds ratio [OR], 1.41; 95% CI, 1.03-1.92; P = .03) and hamstring eccentric strength at 60 deg/s (OR, 1.37; 95% CI, 1.01-1.85; P = .04) adjusted for bodyweight were independently associated with the risk of injuries. The absolute differences between the injured and uninjured players were 6.9 N.m and 9.1 N.m, with small effect sizes (d < 0.2). The ROC analyses showed an area under the curve of 0.54 and 0.56 for quadriceps concentric strength and hamstring eccentric strength, respectively, indicating a failed combined sensitivity and specificity of the 2 strength variables identified in the logistic regression models. CONCLUSION: This study identified small absolute strength differences and a wide overlap of the absolute strength measurements at the group level. The small associations between lower hamstring eccentric strength and lower quadriceps concentric strength with HSIs can only be considered as weak risk factors. The identification of these risk factors still does not allow the identification of individual players at risk. The use of isokinetic testing to determine the association between strength differences and HSIs is not supported. PMID- 27002103 TI - The Effect of Autologous Hamstring Graft Diameter on the Likelihood for Revision of Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Hamstring autografts for anterior cruciate ligament (ACL) reconstruction (ACLR) have become popular in the past 2 decades; however, it is difficult to predict the diameter of the harvested tendons before surgery. Previous biomechanical studies have suggested that a smaller graft diameter leads to a lower load to failure, but clinical studies looking at various predictors for failure, including graft size, have been inconclusive. PURPOSE: To evaluate the relationship of hamstring graft diameter to ACL revision within a large cohort of patients, while controlling for sex, age, body mass index (BMI), and femoral and tibial fixation type. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A case-control study using patients registered in an ACLR registry was conducted. Revision was used as a marker for graft failure. A case was defined as a patient who underwent primary ACLR with a hamstring autograft that was revised during the study period (April 2006 to September 2012). Three controls, defined as patients who underwent primary ACLR with a hamstring autograft that was not revised, were matched to each of the cases according to age, sex, BMI, and femoral and tibial fixation type. Descriptive characteristics were employed, and conditional logistic regression was conducted to produce estimates of odds ratios and 95% CIs. RESULTS: A total of 124 cases and 367 controls were identified. There were no significant differences between cases and controls in the distribution of sex (52.4% male vs 52.9% male, respectively; P = .932), median age (17.6 years [interquartile range (IQR), 15.9-20.4] vs 17.6 years [IQR, 15.9-20.4], respectively; P = .999), median BMI (23.4 kg/m(2) [IQR, 21.5-26.4] vs 23.4 kg/m(2) [IQR, 21.6-25.8], respectively; P = .954), femoral fixation (P = .459), and tibial fixation (P = .766). The mean (+/-SD) graft diameter was 7.9 +/- 0.75 mm in the cases and 8.1 +/- 0.73 mm in the controls. The likelihood of a patient needing revision ACLR in the study cohort was 0.82 times lower (95% CI, 0.68-0.98) for every 0.5-mm increase in the graft diameter from 7.0 to 9.0 mm. CONCLUSION: In this study, within the range of 7.0 to 9.0 mm, there was a 0.82 times lower likelihood of being a revision case with every 0.5 mm incremental increase in graft diameter. PMID- 27002104 TI - Reply to the letter to the editor 'Survival in young adults diagnosed with follicular lymphoma' by Calvo et al. PMID- 27002105 TI - Inhibition of Hedgehog signaling for the treatment of lymphoma and CLL: a phase II study from the LYSA. PMID- 27002106 TI - The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT: a Danish-Canadian study. AB - BACKGROUND: The added diagnostic and prognostic value of routine bone marrow biopsy (BMB) in patients with diffuse large B-cell lymphoma (DLBCL) undergoing positron emission tomography combined with computed tomography (PET/CT) staging is controversial. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL who underwent both staging PET/CT and BMB were retrospectively identified in British Columbia, Aalborg, and Copenhagen. Original written PET/CT and pathology reports were retrospectively reviewed to determine Ann Arbor stage and outcomes, with and without the contribution of BMB. RESULTS: A total of 530 patients were identified: 146 (28%) had focal bone marrow (BM) lesions on PET/CT and 87 (16%) had positive BMB. Fifty-two of 146 patients (36%) with positive PET/CT had a positive BMB [39 DLBCL, 13 indolent non-Hodgkin lymphoma (iNHL)], while 35 of 384 patients (9%) with negative PET/CT had positive BMB (12 DLBCL, 23 iNHL). BMB upstaged 12/209 (6%) of stage I/II patients to stage IV, although this was the case for only 3 (1%) patients with DLBCL in the BMB. PET/CT identified BM involvement by BMB with sensitivity 60%, specificity 79%, positive predictive value 36%, and negative predictive value 91%. Concordant histological involvement of the BM by DLBCL was associated with worse overall survival and progression free survival than discordant or no involvement in univariate and multivariate analyses. CONCLUSIONS: In patients with DLBCL, staging PET/CT can miss BM involvement with concordant DLBCL (less common) or discordant iNHL (more common). Routine BMB does not add relevant diagnostic or prognostic value over PET/CT alone in the majority of patients with DLBCL. PMID- 27002107 TI - Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): a randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX. AB - BACKGROUND: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. PATIENTS AND METHODS: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progression-free survival (PFS). Tumour tissues were assessed by next generation sequencing (NGS). This report is the final analysis. RESULTS: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32 1.02); P = 0.056]. CONCLUSIONS: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials. PMID- 27002108 TI - Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. AB - OBJECTIVES: To explore the effects of tofacitinib-an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA)-with or without methotrexate (MTX), on MRI endpoints in MTX-naive adult patients with early active RA and synovitis in an index wrist or hand. METHODS: In this exploratory, phase 2, randomised, double-blind, parallel-group study, patients received tofacitinib 10 mg twice daily + MTX, tofacitinib 10 mg twice daily + placebo (tofacitinib monotherapy), or MTX + placebo (MTX monotherapy), for 1 year. MRI endpoints (Outcome Measures in Rheumatology Clinical Trials RA MRI score (RAMRIS), quantitative RAMRIS (RAMRIQ) and dynamic contrast-enhanced (DCE) MRI) were assessed using a mixed-effect model for repeated measures. Treatment differences with p<0.05 (vs MTX monotherapy) were considered significant. RESULTS: In total, 109 patients were randomised and treated. Treatment differences in RAMRIS bone marrow oedema (BME) at month 6 were -1.55 (90% CI -2.52 to -0.58) for tofacitinib + MTX and -1.74 (-2.72 to -0.76) for tofacitinib monotherapy (both p<0.01 vs MTX monotherapy). Numerical improvements in RAMRIS synovitis at month 3 were -0.63 ( 1.58 to 0.31) for tofacitinib + MTX and -0.52 (-1.46 to 0.41) for tofacitinib monotherapy (both p>0.05 vs MTX monotherapy). Treatment differences in RAMRIQ synovitis were statistically significant at month 3, consistent with DCE MRI findings. Less deterioration of RAMRIS and RAMRIQ erosive damage was seen at months 6 and 12 in both tofacitinib groups versus MTX monotherapy. CONCLUSIONS: These results provide consistent evidence using three different MRI technologies that tofacitinib treatment leads to early reduction of inflammation and inhibits progression of structural damage. TRIAL REGISTRATION NUMBER: NCT01164579. PMID- 27002114 TI - Openness and honesty when things go wrong: the professional duty of candour (GMC guideline). PMID- 27002113 TI - Genetic manipulation for inherited neurodegenerative diseases: myth or reality? AB - Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. PMID- 27002116 TI - Neutrophil heterogeneity: implications for homeostasis and pathogenesis. AB - Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a homogenous population of terminally differentiated cells with a well-defined and highly conserved function. Indeed, their short lifespan, the absent proliferative capacity, their limited ability to produce large amounts of cytokines, and the failure to recirculate from the tissue to the bloodstream have sustained this idea. However, increasing evidence over the last decade has demonstrated an unexpected phenotypic heterogeneity and functional versatility of the neutrophil population. Far beyond their antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. These emerging discoveries open a new door to understand the role of neutrophils during homeostatic but also pathogenic immune processes. Thus, this review details novel insights of neutrophil phenotypic and functional heterogeneity during homeostasis and disease. PMID- 27002115 TI - Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. AB - The International Myeloma Working Group consensus updates the definition for high risk (HR) multiple myeloma based on cytogenetics Several cytogenetic abnormalities such as t(4;14), del(17/17p), t(14;16), t(14;20), nonhyperdiploidy, and gain(1q) were identified that confer poor prognosis. The prognosis of patients showing these abnormalities may vary with the choice of therapy. Treatment strategies have shown promise for HR cytogenetic diseases, such as proteasome inhibition in combination with lenalidomide/pomalidomide, double autologous stem cell transplant plus bortezomib, or combination of immunotherapy with lenalidomide or pomalidomide. Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. Cross-trial comparisons may provide insight into the effect of new drugs in patients with cytogenetic abnormalities. However, to achieve this, consensus on definitions of analytical techniques, proportion of abnormal cells, and treatment regimens is needed. Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p), whereas lenalidomide may be associated with improved progression-free survival in t(4;14) and del(17/17p). Patients with multiple adverse cytogenetic abnormalities do not benefit from these agents. FISH data are implemented in the revised International Staging System for risk stratification. PMID- 27002117 TI - VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. AB - The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamide dexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P = .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P = .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT. This trial was registered at www.clinicaltrials.gov as #NCT01564537 and at EudraCT as #2013-003174-27. PMID- 27002118 TI - Cardiolipin-mediated procoagulant activity of mitochondria contributes to traumatic brain injury-associated coagulopathy in mice. AB - Cardiolipin (CL) is an anionic phospholipid located exclusively in the mitochondrial inner membrane. Its presence in blood indicates mitochondrial damage and release from injured cells. Here, we report the detection of CL exposed brain-derived mitochondrial microparticles (mtMPs) at 17 547 +/- 2677/MUL in the peripheral blood of mice subjected to fluid percussion injury to the brain. These mtMPs accounted for 55.2% +/- 12.6% of all plasma annexin V-binding microparticles found in the acute phase of injury. They were also released from cultured neuronal and glial cells undergoing apoptosis. The mtMPs synergized with platelets to facilitate vascular leakage by disrupting the endothelial barrier. The disrupted endothelial barrier allowed the release of mtMPs into the systemic circulation to promote coagulation in both traumatically injured and mtMP- or CL injected mice, leading to enhanced fibrinolysis, vascular fibrin deposition, and thrombosis. This mtMP-induced coagulation was mediated by CL transported from the inner to the outer mitochondrial membrane and was blocked by the scavenging molecule lactadherin. The mtMP-bound CL was ~1600 times as active as purified CL in promoting coagulation. This study uncovered a novel procoagulant activity of CL and CL-exposed mitochondria that may contribute to traumatic brain injury associated coagulopathy and identified potential pathways to block this activity. PMID- 27002119 TI - IL-4 enhances expression and function of surface IgM in CLL cells. AB - Kinase inhibitors targeting the B-cell receptor (BCR) are now prominent in the treatment of chronic lymphocytic leukemia (CLL). We have focused here on interleukin 4 (IL-4), a cytokine that protects normal and malignant B cells from apoptosis and increases surface immunoglobulin M (sIgM) expression on murine splenic B cells. First, we have demonstrated that IL-4 treatment increased sIgM expression in vitro on peripheral blood B cells obtained from healthy individuals. In CLL, IL-4 target genes are overexpressed in cells purified from the lymph nodes of patients compared with cells derived from matched blood and bone marrow samples. As for normal B cells, IL-4 increased sIgM expression on CLL cells in vitro, especially in samples expressing unmutated V-genes. IL-4-induced sIgM expression was associated with increased receptor signalling activity, measured by anti-IgM-induced calcium mobilization, and with increased expression of CD79B messenger RNA and protein, and the "mature" glycoform of sIgM. Importantly, the ability of the BCR-associated kinase inhibitors idelalisib and ibrutinib, approved for treatment of CLL and other B-cell malignancies, to inhibit anti-IgM-induced signalling was reduced following IL-4 pretreatment in samples from the majority of patients. In contrast to stimulatory effects on sIgM, IL-4 decreased CXCR4 and CXCR5 expression; therefore, CLL cells, particularly within the progressive unmutated V-gene subset, may harness the ability of IL-4 to promote BCR signalling and B-cell retention within lymph nodes. Effects of IL-4 were mediated via JAK3/STAT6 and we propose a potential role for JAK inhibitors in combination with BCR kinase inhibitors for the treatment of CLL. PMID- 27002122 TI - Nearly half of general practices are failing to investigate complaints properly. PMID- 27002121 TI - Invasive coronary imaging: any role in primary and secondary prevention? AB - This review discusses the possibilities offered by new modalities of non-invasive and invasive coronary imaging in an effort to optimize risk stratification for coronary artery disease, and identify subgroups at high risk that may benefit from an aggressive, personalized approach, with access to a growing number of novel drugs and interventions. Special emphasis is placed on the progress of novel invasive imaging techniques such as near infrared spectroscopy and optical coherence tomography that can reliably identify thin-capped fibroatheromas. Multiple trials are exploring the feasibility of these techniques to guide modulation of risk factor control and treatment of non-flow limiting lesions at high risk of destabilization and progression in patients undergoing clinically mandated angioplasty of angiographically critical lesions. Asymptomatic patients at high risk of cardiovascular ischaemic events may also benefit, with the intermediate step of a wider application of calcium score and angiography with multi-slice computed tomography, by a selective use of invasive imaging. PMID- 27002123 TI - Risky, Impulsive, and Self-Destructive Behavior Questionnaire (RISQ): A Validation Study. AB - Risky behaviors increase the likelihood of premature death, long-term disability, and poor mental health outcomes. Most current measures of risky behavior only assess behaviors within a single domain, fail to evaluate affective triggers for engaging in these behaviors, do not index the consequences of these behaviors, and are often limited to a narrow developmental period. The present study developed and evaluated a new 38-item questionnaire-based measure, the Risky, Impulsive, and Self-Destructive Behavior Questionnaire (RISQ), designed to address each of these limitations by expanding the breadth and depth of previous questionnaires. A bifactor model with a general factor and eight domain-specific factors (measuring drug use, aggression, self-harm, gambling, risky sexual behavior, impulsive eating, heavy alcohol use, and reckless behavior) best fit the RISQ, and indicators of internal consistency, as well as, construct validity were strong. Results provide initial validation for the RISQ as a broad, yet relatively brief, measure that quantifies and qualifies risky behaviors by assessing the severity, chronicity, and triggers for a range of harmful behaviors. PMID- 27002125 TI - Environment may play significant role in multiple sclerosis. PMID- 27002124 TI - Higher and Lower Order Factor Analyses of the Temperament in Middle Childhood Questionnaire. AB - The Temperament in Middle Childhood Questionnaire (TMCQ) is a widely used parent report measure of temperament. However, neither its lower nor higher order structures has been tested via a bottom-up, empirically based approach. We conducted higher and lower order exploratory factor analyses (EFAs) of the TMCQ in a large ( N = 654) sample of 9-year-olds. Item-level EFAs identified 92 items as suitable (i.e., with loadings >=.40) for constructing lower order factors, only half of which resembled a TMCQ scale posited by the measure's authors. Higher order EFAs of the lower order factors showed that a three-factor structure (Impulsivity/Negative Affectivity, Negative Affectivity, and Openness/Assertiveness) was the only admissible solution. Overall, many TMCQ items did not load well onto a lower order factor. In addition, only three factors, which did not show a clear resemblance to Rothbart's four-factor model of temperament in middle childhood, were needed to account for the higher order structure of the TMCQ. PMID- 27002126 TI - Compact and High Performance Spectrometers based on Novel Transmission Gratings with High Dispersion. AB - In this article we outline how ultra-compact, yet high performance spectrometers can be designed and built with highly dispersive transmission gratings. By using fused silica as the grating material, and by careful design of the detailed grating structure, we demonstrate an ultraviolet spectrometer with a high and nearly flat efficiency from 178 to 409 nm, a resolution of 0.2 nm, and dimensions of only 61 mm * 64 mm * 19 mm. We tested this spectrometer in a laser-induced breakdown spectroscopy experiment and showed that the spectral information gathered with the spectrometer can be used to obtain quantitative results for sulfur. PMID- 27002128 TI - Identification of the Three Genes Involved in Controlling Production of a Phytotoxin Tropolone in Burkholderia plantarii. AB - Tropolone, a phytotoxin produced by Burkholderia plantarii, causes rice seedling blight. To identify genes involved in tropolone synthesis, we systematically constructed mutations in the genes encoding 55 histidine kinases and 72 response regulators. From the resulting defective strains, we isolated three mutants, KE1, KE2, and KE3, in which tropolone production was repressed. The deleted genes of these mutants were named troR1, troK, and troR2, respectively. The mutant strains did not cause rice seedling blight, and complementation experiments indicated that TroR1, TroK, and TroR2 were involved in the synthesis of tropolone in B. plantarii However, tropolone synthesis was repressed in the TroR1 D52A, TroK H253A, and TroR2 D46A site-directed mutants. These results suggest that the putative sensor kinase (TroK) and two response regulators (TroR1 and TroR2) control the production of tropolone in B. plantarii IMPORTANCE: A two-component system is normally composed of a sensor histidine kinase (HK) and a cognate response regulator (RR) pair. In this study, HK (TroK) and two RRs (TroR1 and TroR2) were found to be involved in controlling tropolone production in B. plantarii These three genes may be part of a bacterial signal transduction network. Such networks are thought to exist in other bacteria to regulate phytotoxin production, as well as environmental adaptation and signal transduction. PMID- 27002127 TI - The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress. AB - Cytoplasmic chemoreceptors are widespread among prokaryotes but are far less understood than transmembrane chemoreceptors, despite being implicated in many processes. One such cytoplasmic chemoreceptor is Helicobacter pylori TlpD, which is required for stomach colonization and drives a chemotaxis response to cellular energy levels. Neither the signals sensed by TlpD nor its molecular mechanisms of action are known. We report here that TlpD functions independently of the other chemoreceptors. When TlpD is the sole chemoreceptor, it is able to localize to the pole and recruits CheW, CheA, and at least two CheV proteins to this location. It loses the normal membrane association that appears to be driven by interactions with other chemoreceptors and with CheW, CheV1, and CheA. These results suggest that TlpD can form an autonomous signaling unit. We further determined that TlpD mediates a repellent chemotaxis response to conditions that promote oxidative stress, including being in the presence of iron, hydrogen peroxide, paraquat, and metronidazole. Last, we found that all tested H. pylori strains express TlpD, whereas other chemoreceptors were present to various degrees. Our data suggest a model in which TlpD coordinates a signaling complex that responds to oxidative stress and may allow H. pylori to avoid areas of the stomach with high concentrations of reactive oxygen species. IMPORTANCE: Helicobacter pylori senses its environment with proteins called chemoreceptors. Chemoreceptors integrate this sensory information to affect flagellum-based motility in a process called chemotaxis. Chemotaxis is employed during infection and presumably aids H. pylori in encountering and colonizing preferred niches. A cytoplasmic chemoreceptor named TlpD is particularly important in this process, and we report here that this chemoreceptor is able to operate independently of other chemoreceptors to organize a chemotaxis signaling complex and mediate a repellent response to oxidative stress conditions. H. pylori encounters and must cope with oxidative stress during infection due to oxygen and reactive oxygen species produced by host cells. TlpD's repellent response may allow the bacteria to escape niches experiencing inflammation and elevated reactive oxygen species (ROS) production. PMID- 27002129 TI - AB5 Preassembly Is Not Required for Shiga Toxin Activity. AB - Shiga toxin (Stx)-producing Escherichia coli (STEC) is a major cause of foodborne illness, including the life-threatening complication hemolytic-uremic syndrome. The German outbreak in 2011 resulted in nearly 4,000 cases of infection, with 54 deaths. Two forms of Stx, Stx1 and Stx2, differ in potency, and subtype Stx2a is most commonly associated with fatal human disease. Stx is considered to be an AB5 toxin. The single A (enzymatically active) subunit inhibits protein synthesis by cleaving a catalytic adenine from the eukaryotic rRNA. The B (binding) subunit forms a homopentamer and mediates cellular association and toxin internalization by binding to the glycolipid globotriaosylceramide (Gb3). Both subunits are essential for toxicity. Here we report that unlike other AB5 toxin family members, Stx is produced by STEC as unassembled A and B subunits. A preformed AB5 complex is not required for cellular toxicity or in vivo toxicity to mice, and toxin assembly likely occurs at the cell membrane. We demonstrate that disruption of A- and B-subunit association by use of A-subunit peptides that lack enzymatic activity can protect mice from lethal doses of toxin. Currently, no treatments have been proven to be effective for hemolytic-uremic syndrome. Our studies demonstrate that agents that interfere with A- and B-subunit assembly may have therapeutic potential. Shiga toxin (Stx) produced by pathogenic Escherichia coli is considered to be an AB5 heterohexamer; however, no known mechanisms ensure AB5 assembly. Stx released by E. coli is not in the AB5 conformation and assembles at the receptor interface. Thus, unassembled Stx can impart toxicity. This finding shows that preventing AB5 assembly is a potential treatment for Stx-associated illnesses. IMPORTANCE: Complications due to Shiga toxin are frequently fatal, and at present, supportive care is the only treatment option. Furthermore, antibiotic treatment is contraindicated due to the ability of antibiotics to amplify bacterial expression of Shiga toxin. We report, contrary to prevailing assumptions, that Shiga toxin produced by STEC circulates as unassembled A and B subunits at concentrations that are lethal to mice. Similar to the case for anthrax toxin, assembly occurs on receptors expressed on the surfaces of mammalian target cells. Disruption of Shiga toxin assembly by use of A-subunit peptides that lack enzymatic activity protects mice from lethal challenge with Shiga toxin, suggesting a new approach for development of therapeutics. PMID- 27002130 TI - Transcriptome Analysis of Escherichia coli during dGTP Starvation. AB - Our laboratory recently discovered that Escherichia coli cells starved for the DNA precursor dGTP are killed efficiently (dGTP starvation) in a manner similar to that described for thymineless death (TLD). Conditions for specific dGTP starvation can be achieved by depriving an E. coli optA1 gpt strain of the purine nucleotide precursor hypoxanthine (Hx). To gain insight into the mechanisms underlying dGTP starvation, we conducted genome-wide gene expression analyses of actively growing optA1 gpt cells subjected to hypoxanthine deprivation for increasing periods. The data show that upon Hx withdrawal, the optA1 gpt strain displays a diminished ability to derepress the de novo purine biosynthesis genes, likely due to internal guanine accumulation. The impairment in fully inducing the purR regulon may be a contributing factor to the lethality of dGTP starvation. At later time points, and coinciding with cell lethality, strong induction of the SOS response was observed, supporting the concept of replication stress as a final cause of death. No evidence was observed in the starved cells for the participation of other stress responses, including the rpoS-mediated global stress response, reinforcing the lack of feedback of replication stress to the global metabolism of the cell. The genome-wide expression data also provide direct evidence for increased genome complexity during dGTP starvation, as a markedly increased gradient was observed for expression of genes located near the replication origin relative to those located toward the replication terminus. IMPORTANCE: Control of the supply of the building blocks (deoxynucleoside triphosphates [dNTPs]) for DNA replication is important for ensuring genome integrity and cell viability. When cells are starved specifically for one of the four dNTPs, dGTP, the process of DNA replication is disturbed in a manner that can lead to eventual death. In the present study, we investigated the transcriptional changes in the bacterium E. coli during dGTP starvation. The results show increasing DNA replication stress with an increased time of starvation, as evidenced by induction of the bacterial SOS system, as well as a notable lack of induction of other stress responses that could have saved the cells from cell death by slowing down cell growth. PMID- 27002131 TI - Teichoic Acid Polymers Affect Expression and Localization of dl-Endopeptidase LytE Required for Lateral Cell Wall Hydrolysis in Bacillus subtilis. AB - In Bacillus subtilis, the dl-endopeptidase LytE is responsible for lateral peptidoglycan hydrolysis during cell elongation. We found that sigma(I)-dependent transcription of lytE is considerably enhanced in a strain with a mutation in ltaS, which encodes a major lipoteichoic acid (LTA) synthase. Similar enhancements were observed in mutants that affect the glycolipid anchor and wall teichoic acid (WTA) synthetic pathways. Immunofluorescence microscopy revealed that the LytE foci were considerably increased in these mutants. The localization patterns of LytE on the sidewalls appeared to be helix-like in LTA-defective or WTA-reduced cells and evenly distributed on WTA-depleted or -defective cell surfaces. These results strongly suggested that LTA and WTA affect both sigma(I) dependent expression and localization of LytE. Interestingly, increased LytE localization along the sidewall in the ltaS mutant largely occurred in an MreBH independent manner. Moreover, we found that cell surface decorations with LTA and WTA are gradually reduced at increased culture temperatures and that LTA rather than WTA on the cell surface is reduced at high temperatures. In contrast, the amount of LytE on the cell surface gradually increased under heat stress conditions. Taken together, these results indicated that reductions in these anionic polymers at high temperatures might give rise to increases in SigI dependent expression and cell surface localization of LytE at high temperatures. IMPORTANCE: The bacterial cell wall is required for maintaining cell shape and bearing environmental stresses. The Gram-positive cell wall consists of mesh-like peptidoglycan and covalently linked wall teichoic acid and lipoteichoic acid polymers. It is important to determine if these anionic polymers are required for proliferation and environmental adaptation. Here, we demonstrated that these polymers affect the expression and localization of a peptidoglycan hydrolase LytE required for lateral cell wall elongation. Moreover, we found that cell surface decorations with teichoic acid polymers are substantially decreased at high temperatures and that the peptidoglycan hydrolase is consequently increased. These findings suggest that teichoic acid polymers control lateral peptidoglycan hydrolysis by LytE, and bacteria drastically change their cell wall content to adapt to their environment. PMID- 27002132 TI - Allosteric Activation of Escherichia coli Glucosamine-6-Phosphate Deaminase (NagB) In Vivo Justified by Intracellular Amino Sugar Metabolite Concentrations. AB - We have investigated the impact of growth on glucosamine (GlcN) and N acetylglucosamine (GlcNAc) on cellular metabolism by quantifying glycolytic metabolites in Escherichia coli Growth on GlcNAc increased intracellular pools of both GlcNAc6P and GlcN6P 10- to 20-fold compared to growth on glucose. Growth on GlcN produced a 100-fold increase in GlcN6P but only a slight increase in GlcNAc6P. Changes to the amounts of downstream glycolytic intermediates were minor compared to growth on glucose. The enzyme glucosamine-6P deaminase (NagB) is required for growth on both GlcN and GlcNAc. It is an allosteric enzyme in E. coli, displaying sigmoid kinetics with respect to its substrate, GlcN6P, and is allosterically activated by GlcNAc6P. The high concentration of GlcN6P, accompanied by the small increase in GlcNAc6P, drives E. coli NagB (NagBEc) into its high activity state, as observed during growth on GlcN (L. I. Alvarez-Anorve, I. Bustos-Jaimes, M. L. Calcagno, and J. Plumbridge, J Bacteriol 191:6401-6407, 2009, http://dx.doi.org/10.1128/JB.00633-09). The slight increase in GlcNAc6P during growth on GlcN is insufficient to displace NagC, the GlcNAc6P-responsive repressor of the nag genes, from its binding sites, so there is only a small increase in nagB expression. We replaced the gene for the allosteric NagBEc enzyme with that of the nonallosteric, B. subtilis homologue, NagBBs We detected no effects on growth rates or competitive fitness on glucose or the amino sugars, nor did we detect any effect on the concentrations of central metabolites, thus demonstrating the robustness of amino sugar metabolism and leaving open the question of the role of allostery in the regulation of NagB. IMPORTANCE: Chitin, the polymer of N-acetylglucosamine, is an abundant biomaterial, and both glucosamine and N-acetylglucosamine are valuable nutrients for bacteria. The amino sugars are components of numerous essential macromolecules, including bacterial peptidoglycan and mammalian glycosaminoglycans. Controlling the biosynthetic and degradative pathways of amino sugar metabolism is important in all organisms to avoid loss of nitrogen and energy via a futile cycle of synthesis and breakdown. The enzyme glucosamine-6P deaminase (NagB) is central to this control, and N-acetylglucosamine-6P is the key signaling molecule regulating amino sugar utilization in Escherichia coli Here, we investigate how the metabolic status of the bacteria impacts on the activity of NagBEc and the N acetylglucosamine-6P-sensitive transcriptional repressor, NagC. PMID- 27002133 TI - Effects of Lipopolysaccharide Core Sugar Deficiency on Colanic Acid Biosynthesis in Escherichia coli. AB - When 10 Escherichia coli mutant strains with defects in lipopolysaccharide (LPS) core biosynthesis were grown on agar medium at 30 degrees C, four of them, the DeltawaaF, DeltawaaG, DeltawaaP, and DeltawaaB strains, formed mucoid colonies, while the other six, the DeltawaaU, DeltawaaR, DeltawaaO, DeltawaaC, DeltawaaQ, and DeltawaaY strains, did not. Using light microscopy with tannin mordant staining, the presence of exopolysaccharide around the cells of the mutants that formed mucoid colonies could be discerned. The DeltawaaF mutant produced the largest amounts of exopolysaccharide, regardless of whether it was grown on agar or in liquid medium. The exopolysaccharide was isolated from the liquid growth medium of DeltawaaF cells, hydrolyzed, and analyzed by high-performance liquid chromatography with an ion-exchange column, and the results indicated that the exopolysaccharide was consistent with colanic acid. When the key genes related to the biosynthesis of colanic acid, i.e., wza, wzb, wzc, and wcaA, were deleted in the DeltawaaF background, the exopolysaccharide could not be produced any more, further confirming that it was colanic acid. Colanic acid could not be produced in strains in which rcsA, rcsB, rcsD, or rcsF was deleted in the DeltawaaF background, but a reduced level of colanic acid production was detected when the rcsC gene was deleted, suggesting that a change of lipopolysaccharide structure in DeltawaaF cells might be sensed by the RcsCDB phosphorelay system, leading to the production of colanic acid. The results demonstrate that E. coli cells can activate colanic acid production through the RcsCDB phosphorelay system in response to a structural deficiency of lipopolysaccharide. IMPORTANCE: Lipopolysaccharide and colanic acid are important forms of exopolysaccharide for Escherichia coli cells. Their metabolism and biological significance have been investigated, but their interrelation with the cell stress response process is not understood. This study demonstrates, for the first time, that E. coli cells can activate colanic acid production through the RcsCDB phosphorelay system in response to a structural change of lipopolysaccharide, suggesting that bacterial cells can monitor the outer membrane integrity, which is essential for cell survival and damage repair. PMID- 27002134 TI - Rv2744c Is a PspA Ortholog That Regulates Lipid Droplet Homeostasis and Nonreplicating Persistence in Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a significant cause of morbidity and mortality worldwide, despite the availability of a live attenuated vaccine and anti-TB antibiotics. The vast majority of individuals infected with M. tuberculosis develop an asymptomatic latent infection in which the bacterium survives within host-generated granulomatous lesions in a physiologically altered metabolic state of nonreplicating persistence. The granuloma represents an adverse environment, as M. tuberculosis is exposed to various stressors capable of disrupting the essential constituents of the bacterium. In Gram-negative and Gram-positive bacteria, resistance to cell envelope stressors that perturb the plasma membrane is mediated in part by proteins comprising the phage shock protein (Psp) system. PspA is an important component of the Psp system; in the presence of envelope stress, PspA localizes to the inner face of the plasma membrane, homo-oligomerizes to form a large scaffold-like complex, and helps maintain plasma membrane integrity to prevent a loss of proton motive force. M. tuberculosis and other members of the Mycobacterium genus are thought to encode a minimal functional unit of the Psp system, including an ortholog of PspA. Here, we show that Rv2744c possesses structural and physical characteristics that are consistent with its designation as a PspA family member. However, although Rv2744c is upregulated under conditions of cell envelope stress, loss of Rv2744c does not alter resistance to cell envelope stressors. Furthermore, Rv2744c localizes to the surface of lipid droplets in Mycobacterium spp. and regulates lipid droplet number, size, and M. tuberculosis persistence during anaerobically induced dormancy. Collectively, our results indicate that Rv2744c is a bona fide ortholog of PspA that may function in a novel role to regulate lipid droplet homeostasis and nonreplicating persistence (NRP) in M. tuberculosis IMPORTANCE: Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease associated with significant morbidity and mortality worldwide. M. tuberculosis is capable of establishing lifelong asymptomatic infections in susceptible individuals and reactivating during periods of immune suppression to cause active disease. The determinants that are important for persistent infection of M. tuberculosis or for reactivation of this organism from latency are poorly understood. In this study, we describe our initial characterizations of Rv2744c, an ortholog of phage shock protein A (PspA) that regulates the homeostasis of lipid bodies and nonreplicating persistence in M. tuberculosis This function of PspA in M. tuberculosis is novel and suggests that PspA may represent a unique bacterial target upon which to base therapeutic interventions against this organism. PMID- 27002135 TI - The Inhibitory Site of a Diguanylate Cyclase Is a Necessary Element for Interaction and Signaling with an Effector Protein. AB - Many bacteria contain large cyclic diguanylate (c-di-GMP) signaling networks made of diguanylate cyclases (DGCs) and phosphodiesterases that can direct cellular activities sensitive to c-di-GMP levels. While DGCs synthesize c-di-GMP, many DGCs also contain an autoinhibitory site (I-site) that binds c-di-GMP to halt excess production of this small molecule, thus controlling the amount of c-di-GMP available to bind to target proteins in the cell. Many DGCs studied to date have also been found to signal for a specific c-di-GMP-related process, and although recent studies have suggested that physical interaction between DGCs and target proteins may provide this signaling fidelity, the importance of the I-site has not yet been incorporated into this model. Our results from Pseudomonas fluorescens indicate that mutation of residues at the I-site of a DGC disrupts the interaction with its target receptor. By creating various substitutions to a DGC's I-site, we show that signaling between a DGC (GcbC) and its target protein (LapD) is a combined function of the I-site-dependent protein-protein interaction and the level of c-di-GMP production. The dual role of the I-site in modulating DGC activity as well as participating in protein-protein interactions suggests caution in interpreting the function of the I-site as only a means to negatively regulate a cyclase. These results implicate the I-site as an important positive and negative regulatory element of DGCs that may contribute to signaling specificity. IMPORTANCE: Some bacteria contain several dozen diguanylate cyclases (DGCs), nearly all of which signal to specific receptors using the same small molecule, c-di-GMP. Signaling specificity in these networks may be partially driven by physical interactions between DGCs and their receptors, in addition to the autoinhibitory site of DGCs preventing the overproduction of c-di-GMP. In this study, we show that disruption of the autoinhibitory site of a DGC in Pseudomonas fluorescens can result in the loss of interactions with its target receptor and reduced biofilm formation, despite increased production of c-di-GMP. Our findings implicate the autoinhibitory site as both an important feature for signaling specificity through the regulation of c-di-GMP production and a necessary element for the physical interaction between a diguanylate cyclase and its receptor. PMID- 27002136 TI - Brief Online Mindfulness Training: Immediate Impact. AB - BACKGROUND: Online training is feasible, but the impact of brief mindfulness training on health professionals needs to be better understood. METHODS: We analyzed data from health professionals and trainees who completed self reflection exercises embedded in online mindfulness training between May 2014 and September, 2015; their changes in mindfulness were measured using standardized scales. RESULTS: Participants included nurses (34%), physicians (24%), social workers and psychologists (10%), dietitians (8%), and others (25%); 85% were women, and 20% were trainees. The most popular module was Introduction to Mindfulness (n = 161), followed by Mindfulness in Daily Life (n = 146), and Mindful Breathing and Walking (n = 129); most (68%) participants who took 1 module took all 3 modules. There were no differences in participation in any module by gender, trainee status, or profession. Completing modules was associated with small but significant improvements on the Cognitive and Affective Mindfulness Scale-Revised, the Mindful Attention Awareness Scale, and the Five Facet Mindfulness Questionnaire (P < 0.001 for all). CONCLUSION: Online training reaches diverse health professionals and is associated with immediate improvements in mindfulness. Additional research is warranted to compare the long term cost-effectiveness of different doses of online and in-person mindfulness training on clinician burnout and quality of care. PMID- 27002137 TI - Cross-Validation of the Implementation Leadership Scale (ILS) in Child Welfare Service Organizations. AB - The Implementation Leadership Scale (ILS) is a brief, pragmatic, and efficient measure that can be used for research or organizational development to assess leader behaviors and actions that actively support effective implementation of evidence-based practices (EBPs). The ILS was originally validated with mental health clinicians. This study validates the ILS factor structure with providers in community-based organizations (CBOs) providing child welfare services. Participants were 214 service providers working in 12 CBOs that provide child welfare services. All participants completed the ILS, reporting on their immediate supervisor. Confirmatory factor analyses were conducted to examine the factor structure of the ILS. Internal consistency reliability and measurement invariance were also examined. Confirmatory factor analyses showed acceptable fit to the hypothesized first- and second-order factor structure. Internal consistency reliability was strong and there was partial measurement invariance for the first-order factor structure when comparing child welfare and mental health samples. The results support the use of the ILS to assess leadership for implementation of EBPs in child welfare organizations. PMID- 27002138 TI - Update on hypertension: target blood pressure, comorbidities, and outcome. PMID- 27002139 TI - CardioPulse. The SPRINT trial results. PMID- 27002140 TI - Multi-vendor, multicentre comparison of contrast-enhanced SSFP and T2-STIR CMR for determining myocardium at risk in ST-elevation myocardial infarction. AB - AIMS: Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2 short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2 STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi vendor settings. METHODS AND RESULTS: A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1-8 days. These patients participated in the MITOCARE or CHILL-MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 +/- 6%, P = 0.96, r(2) = 0.71, P < 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44). CONCLUSION: In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials. PMID- 27002141 TI - Comparison of SAPIEN 3 and SAPIEN XT transcatheter heart valve stent-frame expansion: evaluation using multi-slice computed tomography. AB - AIMS: Stent-frame morphology of the newer-generation, balloon-expandable transcatheter heart valve (THV), the SAPIEN 3 (S3), after transcatheter aortic valve implantation (TAVI) is unknown. We evaluated the THV stent-frame morphology post TAVI of the S3 using multi-slice computed tomography (MSCT) compared with the prior-generation THV, SAPIEN XT (S-XT). METHODS AND RESULTS: A total of 94 consecutive participants of RESOLVE registry (NCT02318342) had MSCT after balloon expandable TAVI (S3 = 39 and S-XT = 55). The morphology of the THV stent-frame was evaluated for expansion area and eccentricity at the THV-inflow, native annulus, mid-THV and THV-outflow levels. Mean %-expansion area for the S3 and the S-XT was 100.9 +/- 5.7 and 96.1 +/- 5.5%, respectively (P < 0.001). In the S3 group, the THV-inflow level had the largest value of %-expansion area, which decreased from THV-inflow to mid-THV level (105.2 +/- 6.4 to 96.5 +/- 5.9%, P < 0.001). However, in the S-XT group, %-expansion area increased from THV-inflow level to mid-THV level (93.2 +/- 6.2 to 95.1 +/- 6.1%, P = 0.0058). On nominal delivery balloon volume, the S3 in 88.5% of cases had overexpansion at the THV inflow level. The observed degree of THV oversizing of the S3 was significantly lower than the S-XT (6.3 +/- 8.6 vs. 11.8 +/- 8.5%, P = 0.0027). Nonetheless, the incidence of post-procedural paravalvular aortic regurgitation (PVR) >= mild following the S3 TAVI was also significantly lower than the S-XT TAVI (17.9 vs. 43.6%, P = 0.014). CONCLUSION: The newer-generation, balloon-expandable device, the S3, has a flared inflow morphology, whereas the prior-generation device, the S-XT, has relatively constrained inflow morphology post TAVI. This may contribute to a lesser degree of PVR with the S3. PMID- 27002142 TI - Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells. AB - Parthenolide (PTL), a major active sesquiterpene lactone from the herbal plant Tanacetum parthenium, has been applied in traditional Chinese medicine for centuries. Although PTL demonstrates potent anticancer efficacy in numerous types of malignant cells, the cellular targets of PTL have not been well defined. We reported here that PTL interacts with both cytosolic thioredoxin reductase (TrxR1) and mitochondrial thioredoxin reductase (TrxR2), two ubiquitous selenocysteine-containing antioxidant enzymes, to elicit reactive oxygen species mediated apoptosis in HeLa cells. PTL selectively targets the selenocysteine residue in TrxR1 to inhibit the enzyme function, and further shifts the enzyme to an NADPH oxidase to generate superoxide anions, leading to reactive oxygen species accumulation and oxidized thioredoxin. Under the conditions of inhibition of TrxRs in cells, PTL does not cause significant alteration of cellular thiol homeostasis, supporting selective target of TrxRs by PTL. Importantly, overexpression of functional TrxR1 or Trx1 confers protection, whereas knockdown of the enzymes sensitizes cells to PTL treatment. Targeting TrxRs by PTL thus discloses an unprecedented mechanism underlying the biological activity of PTL, and provides deep insights to understand the action of PTL in treatment of cancer. PMID- 27002143 TI - IQ Motif and SEC7 Domain-containing Protein 3 (IQSEC3) Interacts with Gephyrin to Promote Inhibitory Synapse Formation. AB - Gephyrin is a central scaffold protein that mediates development, function, and plasticity of mammalian inhibitory synapses by interacting with various inhibitory synaptic proteins. Here, we show that IQSEC3, a guanine nucleotide exchange factor for ARF6, directly interacts with gephyrin, an interaction that is critical for the inhibitory synapse localization of IQSEC3. Overexpression of IQSEC3 increases inhibitory, but not excitatory, synapse density in a guanine nucleotide exchange factor activity-dependent manner. Conversely, knockdown of IQSEC3 decreases size of gephyrin cluster without altering gephyrin puncta density. Collectively, these data reveal that IQSEC3 acts together with gephyrin to regulate inhibitory synapse development. PMID- 27002144 TI - Human Cells Cultured under Physiological Oxygen Utilize Two Cap-binding Proteins to recruit Distinct mRNAs for Translation. AB - Translation initiation is a focal point of translational control and requires the binding of eIF4E to the 5' cap of mRNA. Under conditions of extreme oxygen depletion (hypoxia), human cells repress eIF4E and switch to an alternative cap dependent translation mediated by a homolog of eIF4E, eIF4E2. This homolog forms a complex with the oxygen-regulated hypoxia-inducible factor 2alpha and can escape translation repression. This complex mediates cap-dependent translation under cell culture conditions of 1% oxygen (to mimic tumor microenvironments), whereas eIF4E mediates cap-dependent translation at 21% oxygen (ambient air). However, emerging evidence suggests that culturing cells in ambient air, or "normoxia," is far from physiological or "normal." In fact, oxygen in human tissues ranges from 1-11% or "physioxia." Here we show that two distinct modes of cap-dependent translation initiation are active during physioxia and act on separate pools of mRNAs. The oxygen-dependent activities of eIF4E and eIF4E2 are elucidated by observing their polysome association and the status of mammalian target of rapamycin complex 1 (eIF4E-dependent) or hypoxia-inducible factor 2alpha expression (eIF4E2-dependent). We have identified oxygen conditions where eIF4E is the dominant cap-binding protein (21% normoxia or standard cell culture conditions), where eIF4E2 is the dominant cap-binding protein (1% hypoxia or ischemic diseases and cancerous tumors), and where both cap-binding proteins act simultaneously to initiate the translation of distinct mRNAs (1-11% physioxia or during development and stem cell differentiation). These data suggest that the physioxic proteome is generated by initiating translation of mRNAs via two distinct but complementary cap-binding proteins. PMID- 27002145 TI - Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1. AB - Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1( /-)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(-/ ) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid beta-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(-/-) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty acid synthase activity could underlie altered energy balance in these mice. PMID- 27002146 TI - Identification and Structural Characterization of an Intermediate in the Folding of the Measles Virus X Domain. AB - Although most proteins fold by populating intermediates, the transient nature of such states makes it difficult to characterize their structures. In this work we identified and characterized the structure of an intermediate of the X domain of phosphoprotein (P) of measles virus. We obtained this result by a combination of equilibrium and kinetic measurements and NMR chemical shifts used as structural restraints in replica-averaged metadynamics simulations. The structure of the intermediate was then validated by rationally designing four mutational variants predicted to affect the stability of this state. These results provide a detailed view of an intermediate state and illustrate the opportunities offered by a synergistic use of experimental and computational methods to describe non-native states at atomic resolution. PMID- 27002147 TI - Up-regulation of Histone Methyltransferase, DOT1L, by Matrix Hyaluronan Promotes MicroRNA-10 Expression Leading to Tumor Cell Invasion and Chemoresistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma. AB - Human head and neck squamous cell carcinoma is a solid tumor malignancy associated with major morbidity and mortality. In this study, we determined that human head and neck squamous cell carcinoma-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by a high level of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. Importantly, matrix hyaluronan (HA) induces the up-regulation of stem cell markers that display the hallmark CSC properties. Histone methyltransferase, DOT1L, is also up-regulated by HA in CSCs (isolated from HSC-3 cells). Further analyses indicate that the stimulation of microRNA-10b (miR-10b) expression is DOT1L-specific and HA/CD44-dependent in CSCs. This process subsequently results in the overexpression of RhoGTPases and survival proteins leading to tumor cell invasion and cisplatin resistance. Treatment of CSCs with DOT1L-specific small interfering RNAs (siRNAs) effectively blocks HA/CD44-mediated expression of DOT1L, miR-10b production, and RhoGTPase/survival protein up-regulation as well as reduces tumor cell invasion and enhances chemosensitivity. CSCs were also transfected with a specific anti miR-10b inhibitor to silence miR-10b expression and block its target functions. Our results demonstrate that the anti-miR-10 inhibitor not only decreases RhoGTPase/survival protein expression and tumor cell invasion, but also increases chemosensitivity in HA-treated CSCs. Taken together, these findings strongly support the contention that histone methyltransferase, DOT1L-associated epigenetic changes induced by HA play pivotal roles in miR-10 production leading to up-regulation of RhoGTPase and survival proteins. All of these events are critically important for the acquisition of cancer stem cell properties, including self-renewal, tumor cell invasion, and chemotherapy resistance in HA/CD44-activated head and neck cancer. PMID- 27002148 TI - A Positive Feed-forward Loop Associating EGR1 and PDGFA Promotes Proliferation and Self-renewal in Glioblastoma Stem Cells. AB - Glioblastomas are the most common primary brain tumors, highly vascularized, infiltrating, and resistant to current therapies. This cancer leads to a fatal outcome in less than 18 months. The aggressive behavior of glioblastomas, including resistance to current treatments and tumor recurrence, has been attributed to glioma stemlike/progenitor cells. The transcription factor EGR1 (early growth response 1), a member of a zinc finger transcription factor family, has been described as tumor suppressor in gliomas when ectopically overexpressed. Although EGR1 expression in human glioblastomas has been associated with patient survival, its precise location in tumor territories as well as its contribution to glioblastoma progression remain elusive. In the present study, we show that EGR1-expressing cells are more frequent in high grade gliomas where the nuclear expression of EGR1 is restricted to proliferating/progenitor cells. We show in primary cultures of glioma stemlike cells that EGR1 contributes to stemness marker expression and proliferation by orchestrating a PDGFA-dependent growth stimulatory loop. In addition, we demonstrate that EGR1 acts as a positive regulator of several important genes, including SHH, GLI1, GLI2, and PDGFA, previously linked to the maintenance and proliferation of glioma stemlike cells. PMID- 27002149 TI - An Intein-based Strategy for the Production of Tag-free Huntingtin Exon 1 Proteins Enables New Insights into the Polyglutamine Dependence of Httex1 Aggregation and Fibril Formation. AB - The first exon of the Huntingtin protein (Httex1) is one of the most actively studied Htt fragments because its overexpression in R6/2 transgenic mice has been shown to recapitulate several key features of Huntington disease. However, the majority of biophysical studies of Httex1 are based on assessing the structure and aggregation of fusion constructs where Httex1 is fused to large proteins, such as glutathione S-transferase, maltose-binding protein, or thioredoxin, or released in solution upon in situ cleavage of these proteins. Herein, we report an intein-based strategy that allows, for the first time, the rapid and efficient production of native tag-free Httex1 with polyQ repeats ranging from 7Q to 49Q. Aggregation studies on these proteins enabled us to identify interesting polyQ length-dependent effects on Httex1 oligomer and fibril formation that were previously not observed using Httex1 fusion proteins or Httex1 proteins produced by in situ cleavage of fusion proteins. Our studies revealed the inability of Httex1-7Q/15Q to undergo amyloid fibril formation and an inverse correlation between fibril length and polyQ repeat length, suggesting possible polyQ length dependent differences in the structural properties of the Httex1 aggregates. Altogether, our findings underscore the importance of working with tag-free Httex1 proteins and indicate that model systems based on non-native Httex1 sequences may not accurately reproduce the effect of polyQ repeat length and solution conditions on Httex1 aggregation kinetics and structural properties. PMID- 27002150 TI - Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production. AB - Metformin is the most commonly prescribed oral anti-diabetic agent worldwide. Surprisingly, about 35% of diabetic patients either lack or have a delayed response to metformin treatment, and many patients become less responsive to metformin over time. It remains unknown how metformin resistance or insensitivity occurs. Recently, we found that therapeutic metformin concentrations suppressed glucose production in primary hepatocytes through AMPK; activation of the cAMP PKA pathway negatively regulates AMPK activity by phosphorylating AMPKalpha subunit at Ser-485, which in turn reduces AMPK activity. In this study, we find that metformin failed to suppress glucose production in primary hepatocytes with constitutively activated PKA and did not improve hyperglycemia in mice with hyperglucagonemia. Expression of the AMPKalpha1(S485A) mutant, which is unable to be phosphorylated by PKA, increased both AMPKalpha activation and the suppression of glucose production in primary hepatocytes treated with metformin. Intriguingly, salicylate/aspirin prevents the phosphorylation of AMPKalpha at Ser 485, blocks cAMP-PKA negative regulation of AMPK, and improves metformin resistance. We propose that aspirin/salicylate may augment metformin's hepatic action to suppress glucose production. PMID- 27002151 TI - Propionate Increases Hepatic Pyruvate Cycling and Anaplerosis and Alters Mitochondrial Metabolism. AB - In mammals, pyruvate kinase (PK) plays a key role in regulating the balance between glycolysis and gluconeogenesis; however, in vivo regulation of PK flux by gluconeogenic hormones and substrates is poorly understood. To this end, we developed a novel NMR-liquid chromatography/tandem-mass spectrometry (LC-MS/MS) method to directly assess pyruvate cycling relative to mitochondrial pyruvate metabolism (VPyr-Cyc/VMito) in vivo using [3-(13)C]lactate as a tracer. Using this approach, VPyr-Cyc/VMito was only 6% in overnight fasted rats. In contrast, when propionate was infused simultaneously at doses previously used as a tracer, it increased VPyr-Cyc/VMito by 20-30-fold, increased hepatic TCA metabolite concentrations 2-3-fold, and increased endogenous glucose production rates by 20 100%. The physiologic stimuli, glucagon and epinephrine, both increased hepatic glucose production, but only glucagon suppressed VPyr-Cyc/VMito These data show that under fasting conditions, when hepatic gluconeogenesis is stimulated, pyruvate recycling is relatively low in liver compared with VMito flux and that liver metabolism, in particular pyruvate cycling, is sensitive to propionate making it an unsuitable tracer to assess hepatic glycolytic, gluconeogenic, and mitochondrial metabolism in vivo. PMID- 27002152 TI - Suppression of WHITE COLLAR-independent frequency Transcription by Histone H3 Lysine 36 Methyltransferase SET-2 Is Necessary for Clock Function in Neurospora. AB - The circadian system in Neurospora is based on the transcriptional/translational feedback loops and rhythmic frequency (frq) transcription requires the WHITE COLLAR (WC) complex. Our previous paper has shown that frq could be transcribed in a WC-independent pathway in a strain lacking the histone H3K36 methyltransferase, SET-2 (su(var)3-9-enhancer-of-zeste-trithorax-2) (1), but the mechanism was unclear. Here we disclose that loss of histone H3K36 methylation, due to either deletion of SET-2 or H3K36R mutation, results in arrhythmic frq transcription and loss of overt rhythmicity. Histone acetylation at frq locus increases in set-2(KO) mutant. Consistent with these results, loss of H3K36 methylation readers, histone deacetylase RPD-3 (reduced potassium dependence 3) or EAF-3 (essential SAS-related acetyltransferase-associated factor 3), also leads to hyperacetylation of histone at frq locus and WC-independent frq expression, suggesting that proper chromatin modification at frq locus is required for circadian clock operation. Furthermore, a mutant strain with three amino acid substitutions (histone H3 lysine 9, 14, and 18 to glutamine) was generated to mimic the strain with hyperacetylation state of histone H3. H3K9QK14QK18Q mutant exhibits the same defective clock phenotype as rpd-3(KO) mutant. Our results support a scenario in which H3K36 methylation is required to establish a permissive chromatin state for circadian frq transcription by maintaining proper acetylation status at frq locus. PMID- 27002153 TI - The Nuclear Receptor Rev-erbalpha Regulates Adipose Tissue-specific FGF21 Signaling. AB - FGF21 is an atypical member of the FGF family that functions as a hormone to regulate carbohydrate and lipid metabolism. Here we demonstrate that the actions of FGF21 in mouse adipose tissue, but not in liver, are modulated by the nuclear receptor Rev-erbalpha, a potent transcriptional repressor. Interrogation of genes induced in the absence of Rev-erbalpha for Rev-erbalpha-binding sites identified betaKlotho, an essential coreceptor for FGF21, as a direct target gene of Rev erbalpha in white adipose tissue but not liver. Rev-erbalpha ablation led to the robust elevated expression of betaKlotho. Consequently, the effects of FGF21 were markedly enhanced in the white adipose tissue of mice lacking Rev-erbalpha. A major Rev-erbalpha-controlled enhancer at the Klb locus was also bound by the adipocytic transcription factor peroxisome proliferator-activated receptor (PPAR) gamma, which regulates its activity in the opposite direction. These findings establish Rev-erbalpha as a specific modulator of FGF21 signaling in adipose tissue. PMID- 27002154 TI - Intrinsic Pleckstrin Homology (PH) Domain Motion in Phospholipase C-beta Exposes a Gbetagamma Protein Binding Site. AB - Mammalian phospholipase C-beta (PLC-beta) isoforms are stimulated by heterotrimeric G protein subunits and members of the Rho GTPase family of small G proteins. Although recent structural studies showed how Galphaq and Rac1 bind PLC beta, there is a lack of consensus regarding the Gbetagamma binding site in PLC beta. Using FRET between cerulean fluorescent protein-labeled Gbetagamma and the Alexa Fluor 594-labeled PLC-beta pleckstrin homology (PH) domain, we demonstrate that the PH domain is the minimal Gbetagamma binding region in PLC-beta3. We show that the isolated PH domain can compete with full-length PLC-beta3 for binding Gbetagamma but not Galphaq, Using sequence conservation, structural analyses, and mutagenesis, we identify a hydrophobic face of the PLC-beta PH domain as the Gbetagamma binding interface. This PH domain surface is not solvent-exposed in crystal structures of PLC-beta, necessitating conformational rearrangement to allow Gbetagamma binding. Blocking PH domain motion in PLC-beta by cross-linking it to the EF hand domain inhibits stimulation by Gbetagamma without altering basal activity or Galphaq response. The fraction of PLC-beta cross-linked is proportional to the fractional loss of Gbetagamma response. Cross-linked PLC-beta does not bind Gbetagamma in a FRET-based Gbetagamma-PLC-beta binding assay. We propose that unliganded PLC-beta exists in equilibrium between a closed conformation observed in crystal structures and an open conformation where the PH domain moves away from the EF hands. Therefore, intrinsic movement of the PH domain in PLC-beta modulates Gbetagamma access to its binding site. PMID- 27002155 TI - Scabin, a Novel DNA-acting ADP-ribosyltransferase from Streptomyces scabies. AB - A bioinformatics strategy was used to identify Scabin, a novel DNA-targeting enzyme from the plant pathogen 87.22 strain of Streptomyces scabies Scabin shares nearly 40% sequence identity with the Pierisin family of mono-ADP ribosyltransferase toxins. Scabin was purified to homogeneity as a 22-kDa single domain enzyme and was shown to possess high NAD(+)-glycohydrolase (Km (NAD) = 68 +/- 3 MUm; kcat = 94 +/- 2 min(-1)) activity with an RSQXE motif; it was also shown to target deoxyguanosine and showed sigmoidal enzyme kinetics (K0.5(deoxyguanosine) = 302 +/- 12 MUm; kcat = 14 min(-1)). Mass spectrometry analysis revealed that Scabin labels the exocyclic amino group on guanine bases in either single-stranded or double-stranded DNA. Several small molecule inhibitors were identified, and the most potent compounds were found to inhibit the enzyme activity with Ki values ranging from 3 to 24 MUm PJ34, a well known inhibitor of poly-ADP-ribosyltransferases, was shown to be the most potent inhibitor of Scabin. Scabin was crystallized, representing the first structure of a DNA-targeting mono-ADP-ribosyltransferase enzyme; the structures of the apo form (1.45 A) and with two inhibitors (P6-E, 1.4 A; PJ34, 1.6 A) were solved. These x-ray structures are also the first high resolution structures of the Pierisin subgroup of the mono-ADP-ribosyltransferase toxin family. A model of Scabin with its DNA substrate is also proposed. PMID- 27002156 TI - Translation Control of Swarming Proficiency in Bacillus subtilis by 5-Amino pentanolylated Elongation Factor P. AB - Elongation factor P (EF-P) accelerates diprolyl synthesis and requires a posttranslational modification to maintain proteostasis. Two phylogenetically distinct EF-P modification pathways have been described and are encoded in the majority of Gram-negative bacteria, but neither is present in Gram-positive bacteria. Prior work suggested that the EF-P-encoding gene (efp) primarily supports Bacillus subtilis swarming differentiation, whereas EF-P in Gram negative bacteria has a more global housekeeping role, prompting our investigation to determine whether EF-P is modified and how it impacts gene expression in motile cells. We identified a 5-aminopentanol moiety attached to Lys(32) of B. subtilis EF-P that is required for swarming motility. A fluorescent in vivo B. subtilis reporter system identified peptide motifs whose efficient synthesis was most dependent on 5-aminopentanol EF-P. Examination of the B. subtilis genome sequence showed that these EF-P-dependent peptide motifs were represented in flagellar genes. Taken together, these data show that, in B. subtilis, a previously uncharacterized posttranslational modification of EF-P can modulate the synthesis of specific diprolyl motifs present in proteins required for swarming motility. PMID- 27002157 TI - Translation Regulation of the Glutamyl-prolyl-tRNA Synthetase Gene EPRS through Bypass of Upstream Open Reading Frames with Noncanonical Initiation Codons. AB - In the integrated stress response, phosphorylation of eIF2alpha (eIF2alpha-P) reduces protein synthesis while concomitantly promoting preferential translation of specific transcripts associated with stress adaptation. Translation of the glutamyl-prolyl-tRNA synthetase gene EPRS is enhanced in response to eIF2alpha-P. To identify the underlying mechanism of translation control, we employed biochemical approaches to determine the regulatory features by which upstream ORFs (uORFs) direct downstream translation control and expression of the EPRS coding region. Our findings reveal that translation of two inhibitory uORFs encoded by noncanonical CUG and UUG initiation codons in the EPRS mRNA 5'-leader serve to dampen levels of translation initiation at the EPRS coding region. By a mechanism suggested to involve increased translation initiation stringency during stress-induced eIF2alpha-P, we observed facilitated ribosome bypass of these uORFs, allowing for increased translation of the EPRS coding region. Importantly, EPRS protein expression is enhanced through this preferential translation mechanism in response to multiple known activators of eIF2alpha-P and likely serves to facilitate stress adaptation in response to a variety of cellular stresses. The rules presented here for the regulated ribosome bypass of noncanonical initiation codons in the EPRS 5'-leader add complexity into the nature of uORF-mediated translation control mechanisms during eIF2alpha-P and additionally illustrate the roles that previously unexamined uORFs with noncanonical initiation codons can play in modulating gene expression. PMID- 27002158 TI - Enhancing NAD+ Salvage Pathway Reverts the Toxicity of Primary Astrocytes Expressing Amyotrophic Lateral Sclerosis-linked Mutant Superoxide Dismutase 1 (SOD1). AB - Nicotinamide adenine dinucleotide (NAD(+)) participates in redox reactions and NAD(+)-dependent signaling pathways. Although the redox reactions are critical for efficient mitochondrial metabolism, they are not accompanied by any net consumption of the nucleotide. On the contrary, NAD(+)-dependent signaling processes lead to its degradation. Three distinct families of enzymes consume NAD(+) as substrate: poly(ADP-ribose) polymerases, ADP-ribosyl cyclases (CD38 and CD157), and sirtuins (SIRT1-7). Because all of the above enzymes generate nicotinamide as a byproduct, mammalian cells have evolved an NAD(+) salvage pathway capable of resynthesizing NAD(+) from nicotinamide. Overexpression of the rate-limiting enzyme in this pathway, nicotinamide phosphoribosyltransferase, increases total and mitochondrial NAD(+) levels in astrocytes. Moreover, targeting nicotinamide phosphoribosyltransferase to the mitochondria also enhances NAD(+) salvage pathway in astrocytes. Supplementation with the NAD(+) precursors nicotinamide mononucleotide and nicotinamide riboside also increases NAD(+) levels in astrocytes. Amyotrophic lateral sclerosis (ALS) is caused by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. Superoxide dismutase 1 (SOD1) mutations account for up to 20% of familial ALS and 1-2% of apparently sporadic ALS cases. Primary astrocytes isolated from mutant human superoxide dismutase 1-overexpressing mice as well as human post-mortem ALS spinal cord-derived astrocytes induce motor neuron death in co-culture. Increasing total and mitochondrial NAD(+) content in ALS astrocytes increases oxidative stress resistance and reverts their toxicity toward co cultured motor neurons. Taken together, our results suggest that enhancing the NAD(+) salvage pathway in astrocytes could be a potential therapeutic target to prevent astrocyte-mediated motor neuron death in ALS. PMID- 27002159 TI - Activated alpha2-Macroglobulin Regulates Transcriptional Activation of c-MYC Target Genes through Cell Surface GRP78 Protein. AB - Activated alpha2-macroglobulin (alpha2M*) signals predominantly through cell surface GRP78 (CS-GRP78) to promote proliferation and survival of cancer cells; however, the molecular mechanism remains obscure. c-MYC is an essential transcriptional regulator that controls cell proliferation. We hypothesize that alpha2M*/CS-GRP78-evoked key signaling events are required for transcriptional activation of c-MYC target genes. Activation of CS-GRP78 by alpha2M* requires ligation of the GRP78 primary amino acid sequence (Leu(98)-Leu(115)). After stimulation with alpha2M*, CS-GRP78 signaling activates 3-phosphoinositide dependent protein kinase-1 (PDK1) to induce phosphorylation of PLK1, which in turn induces c-MYC transcription. We demonstrate that PLK1 binds directly to c MYC and promotes its transcriptional activity by phosphorylating Ser(62) Moreover, activated c-MYC is recruited to the E-boxes of target genes FOSL1 and ID2 by phosphorylating histone H3 at Ser(10) In addition, targeting the carboxyl terminal domain of CS-GRP78 with a mAb suppresses transcriptional activation of c MYC target genes and impairs cell proliferation. This work demonstrates that alpha2M*/CS-GRP78 acts as an upstream regulator of the PDK1/PLK1 signaling axis to modulate c-MYC transcription and its target genes, suggesting a therapeutic strategy for targeting c-MYC-associated malignant progression. PMID- 27002160 TI - Three in a row-how sodium ions cross the channel. PMID- 27002161 TI - Does emergency physician empathy reduce thoughts of litigation? A randomised trial. AB - BACKGROUND: We hypothesised the addition of brief empathetic statements to physician-patient interaction might decrease thoughts regarding litigation. METHODS: We enrolled a convenience sample of adults in our emergency department (ED) waiting room into a randomised, double-blind controlled trial. Subjects watched videos of simulated discharge conversations between physicians and patient actors; half of the videos differed only by the inclusion of two brief empathetic statements: verbalisations that (1) the physician recognises that the patient is concerned about their symptoms and (2) the patient knows their typical state of health better than a physician seeing them for the first time and did the right thing by seeking evaluation. After watching the video subjects were asked to score a five-point Likert scale their thoughts regarding suing this physician in the event of a missed outcome leading to lost work (primary outcome), and four measures of satisfaction with the physician encounter (secondary outcomes). RESULTS: We enrolled and randomised 437 subjects. 213 in the empathy group and 208 in the non-empathy group completed the trial. Sixteen subjects did not complete the trial due to computer malfunction or incomplete data sheets. Empathy group subjects reported statistically significant less thoughts of litigation than the non-empathy group (mean Likert scale 2.66 vs 2.95, difference -0.29, 95% CI -0.04 to -0.54, p=0.0176). All four secondary measures of satisfaction with the physician encounter were better in the empathy group. CONCLUSIONS: In this study, the addition of brief empathetic statements to ED discharge scenarios was associated with a statistically significant reduction in thoughts regarding litigation. CLINICAL TRIAL REGISTRATION: NCT01837706. PMID- 27002162 TI - 'You're never making just one decision': exploring the lived experiences of ambulance Emergency Operations Centre personnel. AB - BACKGROUND: The aim of this study was to explore the experiences of ambulance dispatch personnel, identifying key stressors and their impact on staff well being. METHODS: Qualitative methodology was used. Nine semistructured interviews were conducted with National Health Service (NHS) ambulance Emergency Operations Centre (EOC) dispatch personnel in the UK between July and August 2014. Participants were asked about their experiences of the role, stress experienced and current strategies they use to deal with stress. Transcripts were analysed using an inductive, bottom-up thematic analysis. RESULTS: Three key themes were identified: (1) 'How dispatch is perceived by others', (2) 'What dispatch really involves' and (3) 'Dealing with the stresses of dispatch'. All participants expressed pride in their work, but felt overloaded by the workload and undervalued by others. Several sources of additional stress, not directly related to the execution of their work, were identified, including the need to mentally unwind from work at the end of a shift. Participants were able to identify a number of ways in which they currently manage work-related stress, but they also suggested changes the organisation could put in place in order to reduce stress in the working environment. CONCLUSIONS: Building on existing theory on work stress and postwork recovery, it was concluded that EOC dispatch staff require greater support at work, including skills training to promote postshift recovery, in order to reduce the likelihood of sickness absence, and prevent work-related fatigue. PMID- 27002164 TI - Cutting edge science: Laser surgery illuminates viscoelasticity of merotelic kinetochores. AB - Increasing evidence in eukaryotic cells suggests that mechanical forces are essential for building a robust mitotic apparatus and correcting inappropriate chromosome attachments. In this issue, Cojoc et al. (2016. J. Cell Biol., http://dx.doi.org/10.1083/jcb.201506011) use laser microsurgery in vivo to measure and study the viscoelastic properties of kinetochores. PMID- 27002165 TI - Correction: Elevated p62/SQSTM1 determines the fate of autophagy-deficient neural stem cells by increasing superoxide. PMID- 27002163 TI - Laser microsurgery reveals conserved viscoelastic behavior of the kinetochore. AB - Accurate chromosome segregation depends on proper kinetochore-microtubule attachment. Upon microtubule interaction, kinetochores are subjected to forces generated by the microtubules. In this work, we used laser ablation to sever microtubules attached to a merotelic kinetochore, which is laterally stretched by opposing pulling forces exerted by microtubules, and inferred the mechanical response of the kinetochore from its length change. In both mammalian PtK1 cells and in the fission yeast Schizosaccharomyces pombe, kinetochores shortened after microtubule severing. Interestingly, the inner kinetochore-centromere relaxed faster than the outer kinetochore. Whereas in fission yeast all kinetochores relaxed to a similar length, in PtK1 cells the more stretched kinetochores remained more stretched. Simple models suggest that these differences arise because the mechanical structure of the mammalian kinetochore is more complex. Our study establishes merotelic kinetochores as an experimental model for studying the mechanical response of the kinetochore in live cells and reveals a viscoelastic behavior of the kinetochore that is conserved in yeast and mammalian cells. PMID- 27002166 TI - MLL5 maintains spindle bipolarity by preventing aberrant cytosolic aggregation of PLK1. AB - Faithful chromosome segregation with bipolar spindle formation is critical for the maintenance of genomic stability. Perturbation of this process often leads to severe mitotic failure, contributing to tumorigenesis. MLL5 has been demonstrated to play vital roles in cell cycle progression and the maintenance of genomic stability. Here, we identify a novel interaction between MLL5 and PLK1 in the cytosol that is crucial for sustaining spindle bipolarity during mitosis. Knockdown of MLL5 caused aberrant PLK1 aggregation that led to acentrosomal microtubule-organizing center (aMTOC) formation and subsequent spindle multipolarity. Further molecular studies revealed that the polo-box domain (PBD) of PLK1 interacted with a binding motif on MLL5 (Thr887-Ser888-Thr889), and this interaction was essential for spindle bipolarity. Overexpression of wild-type MLL5 was able to rescue PLK1 mislocalization and aMTOC formation in MLL5-KD cells, whereas MLL5 mutants incapable of interacting with the PBD failed to do so. We thus propose that MLL5 preserves spindle bipolarity through maintaining cytosolic PLK1 in a nonaggregated form. PMID- 27002167 TI - Correction: A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. PMID- 27002168 TI - Mother centrioles are kicked out so that starfish zygote can grow. AB - Most oocytes eliminate their centrioles during meiotic divisions through unclear mechanisms. In this issue, Borrego-Pinto et al. (2016. J Cell. Biol. http://dx.doi.org/10.1083/jcb.201510083) show that mother centrioles need to be eliminated from starfish oocytes by extrusion into the polar bodies for successful embryo development. PMID- 27002169 TI - Correction: Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death. PMID- 27002172 TI - Correction: Fat2 acts through the WAVE regulatory complex to drive collective cell migration during tissue rotation. PMID- 27002170 TI - Smoothened determines beta-arrestin-mediated removal of the G protein-coupled receptor Gpr161 from the primary cilium. AB - Dynamic changes in membrane protein composition of the primary cilium are central to development and homeostasis, but we know little about mechanisms regulating membrane protein flux. Stimulation of the sonic hedgehog (Shh) pathway in vertebrates results in accumulation and activation of the effector Smoothened within cilia and concomitant disappearance of a negative regulator, the orphan G protein-coupled receptor (GPCR), Gpr161. Here, we describe a two-step process determining removal of Gpr161 from cilia. The first step involves beta-arrestin recruitment by the signaling competent receptor, which is facilitated by the GPCR kinase Grk2. An essential factor here is the ciliary trafficking and activation of Smoothened, which by increasing Gpr161-beta-arrestin binding promotes Gpr161 removal, both during resting conditions and upon Shh pathway activation. The second step involves clathrin-mediated endocytosis, which functions outside of the ciliary compartment in coordinating Gpr161 removal. Mechanisms determining dynamic compartmentalization of Gpr161 in cilia define a new paradigm for down regulation of GPCRs during developmental signaling from a specialized subcellular compartment. PMID- 27002171 TI - Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo. AB - Increasing evidence implicates Ca(2+) in the control of cell migration. However, the underlying mechanisms are incompletely understood. Acidic Ca(2+) stores are fast emerging as signaling centers. But how Ca(2+) is taken up by these organelles in metazoans and the physiological relevance for migration is unclear. Here, we identify a vertebrate Ca(2+)/H(+)exchanger (CAX) as part of a widespread family of homologues in animals. CAX is expressed in neural crest cells and required for their migration in vivo. It localizes to acidic organelles, tempers evoked Ca(2+) signals, and regulates cell-matrix adhesion during migration. Our data provide new molecular insight into how Ca(2+) is handled by acidic organelles and link this to migration, thereby underscoring the role of noncanonical Ca(2+) stores in the control of Ca(2+)-dependent function. PMID- 27002174 TI - Amplification of actin polymerization forces. AB - The actin cytoskeleton drives many essential processes in vivo, using molecular motors and actin assembly as force generators. We discuss here the propagation of forces caused by actin polymerization, highlighting simple configurations where the force developed by the network can exceed the sum of the polymerization forces from all filaments. PMID- 27002173 TI - Distinct mechanisms eliminate mother and daughter centrioles in meiosis of starfish oocytes. AB - Centriole elimination is an essential process that occurs in female meiosis of metazoa to reset centriole number in the zygote at fertilization. How centrioles are eliminated remains poorly understood. Here we visualize the entire elimination process live in starfish oocytes. Using specific fluorescent markers, we demonstrate that the two older, mother centrioles are selectively removed from the oocyte by extrusion into polar bodies. We show that this requires specific positioning of the second meiotic spindle, achieved by dynein-driven transport, and anchorage of the mother centriole to the plasma membrane via mother-specific appendages. In contrast, the single daughter centriole remaining in the egg is eliminated before the first embryonic cleavage. We demonstrate that these distinct elimination mechanisms are necessary because if mother centrioles are artificially retained, they cannot be inactivated, resulting in multipolar zygotic spindles. Thus, our findings reveal a dual mechanism to eliminate centrioles: mothers are physically removed, whereas daughters are eliminated in the cytoplasm, preparing the egg for fertilization. PMID- 27002177 TI - A review on electronic bio-sensing approaches based on non-antibody recognition elements. AB - In this review, recent advances in the development of electronic detection methodologies based on non-antibody recognition elements such as functional liposomes, aptamers and synthetic peptides are discussed. Particularly, we highlight the progress of field effect transistor (FET) sensing platforms where possible as the number of publications on FET-based platforms has increased rapidly. Biosensors involving antibody-antigen interactions have been widely applied in diagnostics and healthcare in virtue of their superior selectivity and sensitivity, which can be attributed to their high binding affinity and extraordinary specificity, respectively. However, antibodies typically suffer from fragile and complicated functional structures, large molecular size and sophisticated preparation approaches (resource-intensive and time-consuming), resulting in limitations such as short shelf-life, insufficient stability and poor reproducibility. Recently, bio-sensing approaches based on synthetic elements have been intensively explored. In contrast to existing reports, this review provides a comprehensive overview of recent advances in the development of biosensors utilizing synthetic recognition elements and a detailed comparison of their assay performances. Therefore, this review would serve as a good summary of the efforts for the development of electronic bio-sensing approaches involving synthetic recognition elements. PMID- 27002178 TI - Preface. PMID- 27002179 TI - Water sampler. PMID- 27002180 TI - GABAA receptor-mediated neurotransmission: Not so simple after all. AB - GABAA receptors are ligand-gated ion channels that form a fundamental component of inhibitory neurotransmission in the central and peripheral nervous systems. However, since the initial recordings of inhibitory electrical activity of neurons in response to GABA, these receptors have been found to play a more complex role and can, under some circumstances, function in an excitatory manner. This has been demonstrated via electrophysiological recordings conducted in both mature and developing neurons from different brain regions, as well as in various subcellular locations such as dendritic and axonal membranes. The balance between the inhibitory and excitatory effects mediated by GABAA receptor activation depends not only on multiple factors that govern the equilibrium of the transmembrane chloride gradient, but also on bicarbonate concentration. Moreover, electrophysiological and fluorescence measurements have revealed that a spatial distribution of the chloride gradient exists within neurons, which locally influences the effects mediated by GABAA receptor activation. In recent years, it has also become apparent that intra-neuronal chloride concentration is partially regulated by cation-chloride co-transporters (CCCs), in particular NKCC1 and KCC2. The aim of the present commentary is to discuss, in light of the latest findings, potential implications of the tight spatial and temporal regulation of chloride equilibrium in health and disease, as well as its relevance for the therapeutic effects of molecules acting at GABAA receptors. PMID- 27002181 TI - A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials. AB - BACKGROUND: A loss of repolarization reserve due to downregulation of K(+) currents has been observed in cultured ventricular myocytes. A similar reduction of K(+) currents is well documented under numerous pathophysiological conditions. We examined the extent of K(+) current downregulation in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48 h. Current and voltage clamp recordings were made using patch electrodes. Application of NS3623 to coronary-perfused left ventricular wedges resulted in increased phase 1 magnitude, epicardial AP notch and J wave amplitude. Patch clamp measurements of IKr and Ito revealed an increase in the magnitude of both currents. Culturing of Mid ventricular cells resulted in a significant decrease in Ito and IKr density. NS3623 increased Ito from 16.4 +/- 2.23 to 31.8 +/- 4.5 pA/pF, and IKr from 0.28 +/- 0.06 to 0.47 +/- 0.09 pA/pF after 2 days in culture. AP recordings from 2 day cultured cells exhibited a reduced phase 1 repolarization, AP prolongation, and early afterdepolarizations (EADs). NS3623 restored the AP notch and was able to suppress EADs. CONCLUSIONS: NS3623 is a dual Ito and IKr activator. Application of this compound to cells with a reduced repolarization reserve resulted in an increase in these currents and a shortening of AP duration, increase in phase 1 repolarization and suppression of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure. PMID- 27002183 TI - Metabolism meets immunity: The role of free fatty acid receptors in the immune system. AB - There are significant numbers of nutrient sensing G protein-coupled receptors (GPCRs) that can be found in cells of the immune system and in tissues that are involved in metabolic function, such as the pancreas or the intestinal epithelium. The family of free fatty acid receptors (FFAR1-4, GPR84), plus a few other metabolite sensing receptors (GPR109A, GPR91, GPR35) have been for this reason the focus of studies linking the effects of nutrients with immunological responses. A number of the beneficial anti-inflammatory effects credited to dietary fats such as omega-3 fatty acids are attributed to their actions on FFAR4.This might play an important protective role in the development of obesity, insulin resistance or asthma. The role of the short-chain fatty acids resulting from fermentation of fibre by the intestinal microbiota in regulating acute inflammatory responses is also discussed. Finally we assess the therapeutic potential of this family of receptors to treat pathologies where inflammation is a major factor such as type 2 diabetes, whether by the use of novel synthetic molecules or by the modulation of the individual's diet. PMID- 27002184 TI - Hypoxia up-regulates mitochondrial genome-encoded transcripts in Arabidopsis roots. AB - Plants are frequently exposed to limitations in oxygen availability during their lifetime. During evolution, they have developed a number of physiological and morphological adaptations to tolerate oxygen and other stress conditions. These include regulation of growth by gene expression and ATP generation. The regulation of nuclear genes after hypoxia and anoxia is well studied; however, the regulation of mitochondrial genes in response to oxygen stress has not been characterized to date. Therefore, we have established an Arabidopsis mitochondrial genome-specific microarray that accommodates probes for all mitochondrial DNA-encoded genes and conserved open reading frames. Our analysis showed an up-regulation of mitochondrial transcripts in Arabidopsis roots after 48 h of hypoxia. Since no significant difference was detected in the expression of mitochondrial RNA polymerases or the mitochondrial DNA content per cell, we propose a transcriptional mode of induction of mitochondrial gene expression under hypoxia. PMID- 27002185 TI - Transmissible amyloid. AB - There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein-based biomaterials. PMID- 27002186 TI - Oral subchronic toxicity evaluation of a novel antitumor agent 25 methoxydammarane-3, 12, 20-triol from Panax notoginseng in Sprague-Dawley rats. AB - Panax notoginseng and its main active ingredients ginsenosides have long been used as medicines and food additives in China. Comparing with the extensive uses and active researches of P. notoginseng and its products, the side effect and probable toxicity were rare. 25-Methoxydammarane-3,12,20-triol (25-OCH3-PPD), a novel dammarane-type triterpene sapogenin that was first isolated from the extract of P. notoginseng, was proven to have strong antitumor activities against prostate cancer, breast cancer and lung cancer. The aim of the present study was to investigate the potential subchronic toxicity of 25-OCH3-PPD after it was repeatedly orally administered to Sprague-Dawley rats (5/sex/group/each time point) at dose levels of 0, 150, 300 or 600 mg/kg/day for 13 weeks and 4-week recovery. No mortality and treatment-related toxicity effects were observed as a result of the administration of 25-OCH3-PPD at any dose level (150, 300 and 600 mg/kg) for 92 consecutive days. Although there were some statistical changes, such as increased weights in female rats and decreased organ weights and coefficients of the liver, spleen, kidney, and adrenal gland compared with the control group at the corresponding time, the autopsy and histopathological examination of the target organs did not show any abnormal responses. As a result, 25-OCH3-PPD was well tolerated by SD rat at doses of up to 600 mg/kg and that it is a potential candidate for therapeutic use. PMID- 27002182 TI - Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C. AB - Cantharidin is a natural toxin and an active constituent in a traditional Chinese medicine used to treat tumors. Cantharidin acts as a semi-selective inhibitor of PPP-family ser/thr protein phosphatases. Despite sharing a common catalytic mechanism and marked structural similarity with PP1C, PP2AC and PP5C, human PP4C was found to be insensitive to the inhibitory activity of cantharidin. To explore the molecular basis for this selectivity, we synthesized and tested novel C5/C6 derivatives designed from quantum-based modeling of the interactions revealed in the co-crystal structures of PP5C in complex with cantharidin. Structure-activity relationship studies and analysis of high-resolution (1.25A) PP5C-inhibitor co crystal structures reveal close contacts between the inhibitor bridgehead oxygen and both a catalytic metal ion and a non-catalytic phenylalanine residue, the latter of which is substituted by tryptophan in PP4C. Quantum chemistry calculations predicted that steric clashes with the bulkier tryptophan side chain in PP4C would force all cantharidin-based inhibitors into an unfavorable binding mode, disrupting the strong coordination of active site metal ions observed in the PP5C co-crystal structures, thereby rendering PP4C insensitive to the inhibitors. This prediction was confirmed by inhibition studies employing native human PP4C. Mutation of PP5C (F446W) and PP1C (F257W), to mimic the PP4C active site, resulted in markedly suppressed sensitivity to cantharidin. These observations provide insight into the structural basis for the natural selectivity of cantharidin and provide an avenue for PP4C deselection. The novel crystal structures also provide insight into interactions that provide increased selectivity of the C5/C6 modifications for PP5C versus other PPP-family phosphatases. PMID- 27002188 TI - Precipitation shapes communities of arbuscular mycorrhizal fungi in Tibetan alpine steppe. AB - Tibetan Plateau is one of the largest and most unique habitats for organisms including arbuscular mycorrhizal fungi (AMF). However, it remains unclear how AMF communities respond to key environmental changes in this harsh environment. To test if precipitation could be a driving force in shaping AMF community structures at regional scale, we examined AMF communities associated with dominant plant species along a precipitation gradient in Tibetan alpine steppe. Rhizosphere soils were collected from five sites with annual precipitation decreasing from 400 to 50 mm. A total of 31 AMF operational taxonomic units (OTUs) were identified. AMF community composition varied significantly among sites, whereas AMF community composition did not vary among plant species. Path analysis revealed that precipitation directly affected AMF hyphal length density, and indirectly influenced AMF species richness likely through the mediation of plant coverage. Our results suggested that water availability could drive the changes of AMF communities at regional scale. Given the important roles AMF could play in the dynamics of plant communities, exploring the changes of AMF communities along key environmental gradients would help us better predict the ecosystem level responses of the Tibetan vegetation to future climate change. PMID- 27002189 TI - 'Change4Life Smart Swaps': quasi-experimental evaluation of a natural experiment. AB - OBJECTIVE: To evaluate the impact on food purchasing behaviour of the 'Change4Life Smart Swaps' campaign to encourage families to make small changes to lower-fat or lower-sugar versions of commonly eaten foods and drinks. DESIGN: Quasi-experimental study comparing the proportion of swaps made by an intervention group (267 families who had signed up to the 'Smart Swaps' campaign promoted through various media, including television and radio advertising in early 2014) and a comparison group (135 families resident in Wales, signed up for 'Change4Life' materials, but not directly exposed to the 'Smart Swaps' campaign). During weeks 1, 2 and 3 of the campaign participants were asked to record their purchases of dairy products, carbonated drinks and breakfast cereals, using a mobile phone app questionnaire, when making a purchase within the category. SETTING: England and Wales. SUBJECTS: Families registered with 'Change4Life'. RESULTS: In weeks 2 and 3 a significantly higher percentage of the intervention group had made 'smart swaps' than the comparison group. After week 3, 58 % of participants had swapped to a lower-fat dairy product compared with 26 % of the comparison group (P<0.001), 32 % of the intervention group had purchased a lower sugar drink compared with 19 % of the comparison group (P=0.01), and 24 % had made a change to a lower-sugar cereal compared with 12 % of the comparison group (P=0.009). CONCLUSIONS: In the short term a national campaign to change purchase habits towards healthier products may have some merit but the sustainability of change requires further investigation. PMID- 27002190 TI - Unraveling the formation mechanism of graphitic nitrogen-doping in thermally treated graphene with ammonia. AB - Nitrogen-doped graphene (N-graphene) has attractive properties that has been widely studied over the years. However, its possible formation process still remains unclear. Here, we propose a highly feasible formation mechanism of the graphitic-N doing in thermally treated graphene with ammonia by performing ab initio molecular dynamic simulations at experimental conditions. Results show that among the commonly native point defects in graphene, only the single vacancy 5-9 and divacancy 555-777 have the desirable electronic structures to trap N containing groups and to mediate the subsequent dehydrogenation processes. The local structure of the defective graphene in combining with the thermodynamic and kinetic effect plays a crucial role in dominating the complex atomic rearrangement to form graphitic-N which heals the corresponding defect perfectly. The importance of the symmetry, the localized force field, the interaction of multiple trapped N-containing groups, as well as the catalytic effect of the temporarily formed bridge-N are emphasized, and the predicted doping configuration agrees well with the experimental observation. Hence, the revealed mechanism will be helpful for realizing the targeted synthesis of N-graphene with reduced defects and desired properties. PMID- 27002191 TI - N-Adamantyl-4-methylthiazol-2-amine suppresses amyloid beta-induced neuronal oxidative damage in cortical neurons. AB - Recently, we have reported that N-adamantyl-4-methylthiazol-2-amine (KHG26693) successfully reduced the production of oxidative stress in streptozotocin-induced diabetic rats and lipopolysaccharide-induced BV-2 microglial cells by increasing their antioxidant capacity. However, antioxidative effects of KHG26693 against Abeta (Abeta)-induced oxidative stress have not yet been reported. In the present study, we further investigated the antioxidative function of KHG26693 in Abeta mediated primary cultured cortical neurons. We showed here that KHG26693 attenuated Abeta-induced cytotoxicity, increase of Bax/Bcl-2 ratio, elevation of caspase-3 expression, and impairment of mitochondrial membrane potential in cultured primary cortical neurons. KHG26693 also decreases the Abeta-mediated formation of malondialdehyde, reactive oxygen species, and NO production by decreasing nitric oxide synthase (iNOS) and NADPH oxidase level. Moreover, KHG26693 suppress the Abeta-induced oxidative stress through a possible mechanism involving attenuation of GSH and antioxidant enzyme activities such as glutathione reductase and glutathione peroxidase (GPx). Finally, pretreatment of cortical neurons with KHG26693 significantly reduced the Abeta-induced protein oxidation and nitration. To our knowledge, this is the first report, showing that KHG26693 significantly attenuates Abeta-induced oxidative stress in primary cortical neurons, and may prove attractive strategies to reduce Abeta-induced neural cell death. PMID- 27002193 TI - Crowding in the Emergency Department. PMID- 27002187 TI - Understanding craniosynostosis as a growth disorder. AB - Craniosynostosis is a condition of complex etiology that always involves the premature fusion of one or multiple cranial sutures and includes various anomalies of the soft and hard tissues of the head. Steady progress in the field has resulted in identifying gene mutations that recurrently cause craniosynostosis. There are now scores of mutations on many genes causally related to craniosynostosis syndromes, though the genetic basis for the majority of nonsyndromic cases is unknown. Identification of these genetic mutations has allowed significant progress in understanding the intrinsic properties of cranial sutures, including mechanisms responsible for normal suture patency and for pathogenesis of premature suture closure. An understanding of morphogenesis of cranial vault sutures is critical to understanding the pathophysiology of craniosynostosis conditions, but the field is now poised to recognize the repeated changes in additional skeletal and soft tissues of the head that typically accompany premature suture closure. We review the research that has brought an understanding of premature suture closure within our reach. We then enumerate the less well-studied, but equally challenging, nonsutural phenotypes of craniosynostosis conditions that are well characterized in available mouse models. We consider craniosynostosis as a complex growth disorder of multiple tissues of the developing head, whose growth is also targeted by identified mutations in ways that are poorly understood. Knowledge gained from studies of humans and mouse models for these conditions underscores the diverse, associated developmental anomalies of the head that contribute to the complex phenotypes of craniosynostosis conditions presenting novel challenges for future research. WIREs Dev Biol 2016, 5:429-459. doi: 10.1002/wdev.227 For further resources related to this article, please visit the WIREs website. PMID- 27002192 TI - The p-eIF2alpha/ATF4 pathway links endoplasmic reticulum stress to autophagy following the production of reactive oxygen species in mouse spermatocyte-derived cells exposed to dibutyl phthalate. AB - Dibutyl phthalate (DBP) is a widely used plasticizer that has been shown to induce germ cell apoptosis-related testicular atrophy and cause reproductive toxicity. Our previous results indicated that endoplasmic reticulum (ER) stress activated autophagy served as a self-defense mechanism against DBP-induced germ cell apoptosis. However, the specific pathways that link ER stress and autophagy remain unclear. Here, we showed that exposure to DBP enhanced autophagic flux in mouse spermatocyte-derived GC-2 cells and that the eukaryotic translation initiation factor 2/activating transcription factor 4 pathway mediated ER stress related autophagy independent of the mTOR and Beclin-1 pathways. Moreover, we demonstrated that DBP treatment led to the generation of reactive oxygen species (ROS) and that the inhibition of ROS by melatonin abrogated both ER stress and autophagy. The results indicated that excessive ROS production might be involved in DBP-induced ER stress and autophagy in GC-2 cells. Thus, ROS may serve as upstream mediators of ER stress and autophagy in DBP-treated GC-2 cells. PMID- 27002194 TI - Human Trafficking and the Emergency Nurse. PMID- 27002195 TI - Are Peripheral Venous Catheters Necessary in Intensive Care Units? PMID- 27002196 TI - Response. PMID- 27002197 TI - Intravenous Catheters and Blood Samples. PMID- 27002198 TI - Cardiac or Anxiety: A Literature Review of the Young Adult Patient Who Presents to the Emergency Department With Chest Pain. PMID- 27002199 TI - Peer to Peer Education: OB Visits the ED. AB - Ongoing education, an ever-present challenge in a hectic clinical environment, can be addressed by utilizing peer-to-peer education. Enhancing nurses' comfort level with specialty topics can reduce anxiety while enhancing core knowledge and skill proficiency for the provision of safe care. Increased self-confidence in a nurse's ability to detect a new or developing concern can lead to fewer delays in care. Critical problems identified and addressed promptly support better outcomes. PMID- 27002200 TI - After Action Reviews in the Emergency Department: The Positives of Real-Time Feedback. PMID- 27002201 TI - Role Modeling as a Teaching Strategy for the Novice Nurse in the Emergency Department. PMID- 27002202 TI - Adopt the 2016-2017 Targeted Best Practices for Medication Safety. PMID- 27002203 TI - Emergency Nursing Review Questions: March 2016. AB - The review questions that are featured in each of issue of JEN are based on the Emergency Nursing Core Curriculum and other pertinent resources to emergency nursing practice, pediatric and adult. These questions offer emergency nurses an opportunity to test their knowledge about their practice. PMID- 27002204 TI - Whiteboardology. PMID- 27002205 TI - Holistic Care of Older Lesbian, Gay, Bisexual, and Transgender Patients in the Emergency Department. PMID- 27002206 TI - Building the Conversation for Hospital-Based Injury Prevention Program Capacity. PMID- 27002207 TI - Vietnam: A Medical Mission Diary. PMID- 27002208 TI - Hidden Child Abuse Identification in the Emergency Department. PMID- 27002209 TI - The Journey Toward Routinization: Triage Nursing and the Success of an Emergency Department-Based Routine HIV Testing Program. PMID- 27002210 TI - Iron-Carbonyl-Catalyzed Redox-Neutral [4+2] Annulation of N-H Imines and Internal Alkynes by C-H Bond Activation. AB - Stoichiometric C-H bond activation of arenes mediated by iron carbonyls was reported by Pauson as early as in 1965, yet the catalytic C-H transformations have not been developed. Herein, an iron-catalyzed annulation of N-H imines and internal alkynes to furnish cis-3,4-dihydroisoquinolines is described, and represents the first iron-carbonyl-catalyzed C-H activation reaction of arenes. Remarkablely, this is also the first redox-neutral [4+2] annulation of imines and alkynes proceeding by C-H activation. The reaction also features only cis stereoselectivity and excellent atom economy as neither base, nor external ligand, nor additive is required. Experimental and theoretical studies reveal an oxidative addition mechanism for C-H bond activation to afford a dinuclear ferracycle and a synergetic diiron-promoted H-transfer to the alkyne as the turnover-determining step. PMID- 27002211 TI - Risk-preferring rats make worse decisions and show increased incubation of craving after cocaine self-administration. AB - Maladaptive decision-making may play an integral role in the development and maintenance of an addiction. Substance-dependent individuals make riskier choices on the Iowa Gambling Task, and these deficits persist during withdrawal and are predictive of relapse. However, it is unclear from clinical studies whether this cognitive impairment is a cause or consequence of drug use. We trained male Long Evans rats on the rat Gambling Task, a rodent analogue of the Iowa Gambling Task, to determine how choice preference influenced, and was influenced by, cocaine self-administration, withdrawal and incubation of craving. Rats that exhibited a preference for the risky, disadvantageous options at baseline were uniquely and adversely affected by cocaine self-administration. Risky choice was exacerbated in these rats when decision-making was assessed during the same diurnal period as cocaine self-administration, whereas the choice pattern of optimal decision makers was unaffected. This decision-making deficit was maintained during 30 days of withdrawal and correlated with greater cue-induced incubation of craving. Risk preferring rats also made more drug-seeking responses during cocaine self administration. These data demonstrate that poor decision-making prior to contact with addictive drugs is associated with a pro-addictive behavioural phenotype, characterized by further increased risky choice and heightened responding for drug both during cocaine self-administration and withdrawal. Such findings indicate that the elevated risky decision-making observed in substance-dependent populations is not merely circumstantial, but makes an important contribution to addiction vulnerability and severity that can now be effectively modelled in laboratory rats. PMID- 27002212 TI - Portopulmonary hypertension. AB - Portopulmonary hypertension (PoPH) refers to the condition that pulmonary arterial hypertension (PAH) occur in the stetting of portal hypertension. The development of PoPH is thought to be independent of the severity of portal hypertension or the etiology or severity of liver disease. PoPH results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. Untreated PoPH is associated with a poor prognosis. As PoPH is frequently asymptomatic or symptoms are generally non specific, patients should be actively screened for the presence of PoPH. Two dimensional transthoracic echocardiography is a useful non-invasive screening tool, but a definitive diagnosis requires invasive hemodynamic confirmation by right heart catheterization. Despite a dearth of randomized, prospective data, an ever-expanding clinical experience shows that patients with PoPH benefit from therapy with PAH-specific medications including with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and/or prostanoids. Due to high perioperative mortality, transplantation should be avoided in those patients who have severe PoPH that is refractory to medical therapy. PMID- 27002213 TI - The Community Health and Advocacy Milestones Profile: A Novel Tool Linking Community Pediatrics and Advocacy Training to Assessment of Milestones-Based Competence in Pediatric Residency Training. PMID- 27002214 TI - Parental Perceptions of Weight During the First Year of Life. AB - BACKGROUND: More than half of parents underestimate their overweight child's weight; however, previous research focuses on children older than 2 years of age. The objective of this study was to assess whether parents of 2- to 12-month-old infants are able to accurately perceive their children's weight status. METHODS: We performed a cross-sectional analysis of data collected from the Greenlight study, a cluster randomized obesity prevention trial, at 4 pediatric clinics serving diverse and low-income populations. Infants' length and weight were measured at well-child checks, and parents completed questionnaires including demographic characteristics and perception of their children's weight. Weight-for length (WFL) percentile at the fifth to <=95 was considered healthy weight and WFL percentile >95th was considered overweight. We used chi-squared tests to compare accuracy according to weight category and performed logistic regression analysis to assess accuracy at each time point. RESULTS: Approximately 85% to 90% of infants (n = 853 at 2 months, n = 563 at 12 months) were at a healthy WFL at all measurement times, and parents of these infants were more likely to have an accurate perception of their child's weight (accuracy 89%-95%) than overweight children (accuracy 7%-26%; P < .001 across time points). Approximately 10% of healthy weight infants were perceived as underweight by their parents at all time points. At 12 months, mothers who were overweight were significantly more likely to underestimate their child's weight status (P = .008). CONCLUSIONS: In our diverse and low-income sample, parents of overweight infants infrequently know that their infants are overweight. Future studies should examine how perception is related to feeding habits and weight status over time. PMID- 27002215 TI - Can school counselors deliver cognitive-behavioral treatment for social anxiety effectively? A randomized controlled trial. AB - BACKGROUND: Social anxiety disorder (SAD) typically onsets in adolescence and is associated with multiple impairments. Despite promising clinical interventions, most socially anxious adolescents remain untreated. To address this clinical neglect, we developed a school-based, 12-week group intervention for youth with SAD, Skills for Academic and Social Success (SASS). When implemented by psychologists, SASS has been found effective. To promote dissemination and optimize treatment access, we tested whether school counselors could be effective treatment providers. METHOD: We randomized 138, ninth through 11th graders with SAD to one of three conditions: (a) SASS delivered by school counselors (C-SASS), (b) SASS delivered by psychologists (P-SASS), or (c) a control condition, Skills for Life (SFL), a nonspecific counseling program. Blind, independent, evaluations were conducted with parents and adolescents at baseline, post-intervention, and 5 months beyond treatment completion. We hypothesized that C-SASS and P-SASS would be superior to the control, immediately after treatment and at follow-up. No prediction was made about the relative efficacy of C-SASS and P-SASS. RESULTS: Compared to controls, adolescents treated with C-SASS or P-SASS experienced significantly greater improvement and reductions of anxiety at the end of treatment and follow-up. There were no significant differences between SASS delivered by school counselors and psychologists. CONCLUSION: With training, school counselors are effective treatment providers to adolescents with social anxiety, yielding benefits comparable to those obtained by specialized psychologists. Questions remain regarding means to maintain counselors' practice standards without external support. PMID- 27002216 TI - DephosSite: a machine learning approach for discovering phosphotase-specific dephosphorylation sites. AB - Protein dephosphorylation, which is an inverse process of phosphorylation, plays a crucial role in a myriad of cellular processes, including mitotic cycle, proliferation, differentiation, and cell growth. Compared with tyrosine kinase substrate and phosphorylation site prediction, there is a paucity of studies focusing on computational methods of predicting protein tyrosine phosphatase substrates and dephosphorylation sites. In this work, we developed two elegant models for predicting the substrate dephosphorylation sites of three specific phosphatases, namely, PTP1B, SHP-1, and SHP-2. The first predictor is called MGPS DEPHOS, which is modified from the GPS (Group-based Prediction System) algorithm with an interpretable capability. The second predictor is called CKSAAP-DEPHOS, which is built through the combination of support vector machine (SVM) and the composition of k-spaced amino acid pairs (CKSAAP) encoding scheme. Benchmarking experiments using jackknife cross validation and 30 repeats of 5-fold cross validation tests show that MGPS-DEPHOS and CKSAAP-DEPHOS achieved AUC values of 0.921, 0.914 and 0.912, for predicting dephosphorylation sites of the three phosphatases PTP1B, SHP-1, and SHP-2, respectively. Both methods outperformed the previously developed kNN-DEPHOS algorithm. In addition, a web server implementing our algorithms is publicly available at http://genomics.fzu.edu.cn/dephossite/ for the research community. PMID- 27002217 TI - CCAR1 5' UTR as a natural miRancer of miR-1254 overrides tamoxifen resistance. AB - MicroRNAs (miRNAs) typically bind to unstructured miRNA-binding sites in target RNAs, leading to a mutual repression of expression. Here, we report that miR-1254 interacts with structured elements in cell cycle and apoptosis regulator 1 (CCAR1) 5' untranslated region (UTR) and this interaction enhances the stability of both molecules. miR-1254 can also act as a repressor when binding to unstructured sites in its targets. Interestingly, structured miR-1254-targeting sites act as both a functional RNA motif-sensing unit, and an independent RNA functional unit that enhances miR-1254 expression. Artificially designed miRNA enhancers, termed "miRancers", can stabilize and enhance the activity of miRNAs of interest. We further demonstrate that CCAR1 5' UTR as a natural miRancer of endogenous miR-1254 re-sensitizes tamoxifen-resistant breast cancer cells to tamoxifen. Thus, our study presents a novel model of miRNA function, wherein highly structured miRancer-like motif-containing RNA fragments or miRancer molecules specifically interact with miRNAs, leading to reciprocal stabilization. PMID- 27002218 TI - Drugging the undruggables: exploring the ubiquitin system for drug development. AB - Dynamic modulation of protein levels is tightly controlled in response to physiological cues. In mammalian cells, much of the protein degradation is carried out by the ubiquitin-proteasome system (UPS). Similar to kinases, components of the ubiquitin system are often dysregulated, leading to a variety of diseases, including cancer and neurodegeneration, making them attractive drug targets. However, so far there are only a handful of drugs targeting the ubiquitin system that have been approved by the FDA. Here, we review possible therapeutic intervention nodes in the ubiquitin system, analyze the challenges, and highlight the most promising strategies to target the UPS. PMID- 27002219 TI - E2 enzymes: more than just middle men. AB - Ubiquitin-conjugating enzymes (E2s) are the central players in the trio of enzymes responsible for the attachment of ubiquitin (Ub) to cellular proteins. Humans have ~40 E2s that are involved in the transfer of Ub or Ub-like (Ubl) proteins (e.g., SUMO and NEDD8). Although the majority of E2s are only twice the size of Ub, this remarkable family of enzymes performs a variety of functional roles. In this review, we summarize common functional and structural features that define unifying themes among E2s and highlight emerging concepts in the mechanism and regulation of E2s. PMID- 27002220 TI - A positive role for polycomb in transcriptional regulation via H4K20me1. AB - The highly conserved polycomb group (PcG) proteins maintain heritable transcription repression of the genes essential for development from fly to mammals. However, sporadic reports imply a potential role of PcGs in positive regulation of gene transcription, although systematic investigation of such function and the underlying mechanism has rarely been reported. Here, we report a Pc-mediated, H3K27me3-dependent positive transcriptional regulation of Senseless (Sens), a key transcription factor required for development. Mechanistic studies show that Pc regulates Sens expression by promoting H4K20me1 at the Sens locus. Further bioinformatic analysis at genome-wide level indicates that the existence of H4K20me1 acts as a selective mark for positive transcriptional regulation by Pc/H3K27me3. Both the intensities and specific patterns of Pc and H3K27me3 are important for the fates of target gene transcription. Moreover, binding of transcription factor Broad (Br), which physically interacts with Pc and positively regulates the transcription of Sens, is observed in Pc(+)H3K27me3(+)H4K20me1(+) genes, but not in Pc(+)H3K27me3(+)H4K20me1(-) genes. Taken together, our study reveals that, coupling with the transcription factor Br, Pc positively regulates transcription of Pc(+)H3K27me3(+)H4K20me1(+) genes in developing Drosophila wing disc. PMID- 27002221 TI - Towards a structural understanding of allosteric drugs at the human calcium sensing receptor. AB - Drugs that allosterically target the human calcium-sensing receptor (CaSR) have substantial therapeutic potential, but are currently limited. Given the absence of high-resolution structures of the CaSR, we combined mutagenesis with a novel analytical approach and molecular modeling to develop an "enriched" picture of structure-function requirements for interaction between Ca(2+)o and allosteric modulators within the CaSR's 7 transmembrane (7TM) domain. An extended cavity that accommodates multiple binding sites for structurally diverse ligands was identified. Phenylalkylamines bind to a site that overlaps with a putative Ca(2+)o-binding site and extends towards an extracellular vestibule. In contrast, the structurally and pharmacologically distinct AC-265347 binds deeper within the 7TM domains. Furthermore, distinct amino acid networks were found to mediate cooperativity by different modulators. These findings may facilitate the rational design of allosteric modulators with distinct and potentially pathway-biased pharmacological effects. PMID- 27002222 TI - Trauma-Informed Mindfulness-Based Stress Reduction for Female Survivors of Interpersonal Violence: Results From a Stage I RCT. AB - OBJECTIVE: This pilot randomized controlled trial evaluated a novel trauma informed model of mindfulness-based stress reduction (TI-MBSR) as a phase I trauma intervention for female survivors of interpersonal violence (IPV). METHOD: A community-based sample of women (mean age = 41.5, standard deviation = 14.6) with a history of IPV was randomly assigned to an 8-week TI-MBSR intervention (n = 23) or a waitlist control group (n = 22). Symptoms of posttraumatic stress disorder (PTSD) and depression as well as anxious and avoidant attachment were assessed pre- and postintervention. RESULTS: Relative to the control group, participation in TI-MBSR was associated with statistically and clinically significant decreases in PTSD and depressive symptoms and significant reductions in anxious attachment. Retention in the intervention was high, with most participants completing at least 5 of the 8 sessions for the intervention. Minutes of mindfulness practice per week significantly predicted reductions in PTSD symptoms. CONCLUSION: TI-MBSR appears to be a promising and feasible phase I intervention for female survivors of interpersonal trauma. PMID- 27002224 TI - The impact of parenthood on physical aggression: Evidence from criminal data. AB - Evolutionary approaches to sex differences in physical aggression weigh the potential benefits of aggression against the likely costs to inclusive fitness, with some authors focusing on the damage physical injury would do to female inclusive fitness, and others on the extent to which success in physical competition may particularly enhance male fitness. This study tested a hypothesis derived from these approaches: that parents would be less physically aggressive than non-parents because of the damage any physical injury would do to their inclusive fitness. Analysis was carried out using the United States federal sentencing records for 1994-1999 (22,344 individuals). The proportion of theft convictions which were violent (robbery; vs. larceny) was significantly greater for men than women (odds ratio 7.7). As predicted, non-parents were significantly more likely to be violent than parents (odds ratio 1.6). Parenthood had a similar effect on relative rates of violence in men and women, although the baseline was considerably higher for men. There was also a significant effect in men of marital status, which interacted with parental status such that parenthood was only associated with a reduction in rates of violence in males recorded as partnered. The results are interpreted in terms of both evolutionary theory and recent work on the hormonal impacts of marriage and parenthood. Aggr. Behav. 42:577-584, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27002223 TI - Systematic collection of patient reported outcome research data: A checklist for clinical research professionals. AB - Understanding the human experience is no longer an outcome explored strictly by social and behavioral researchers. Increasingly, biomedical researchers are also including patient reported outcomes (PROs) in their clinical research studies not only due to calls for increased patient engagement in research but also healthcare. Collecting PROs in clinical research studies offers a lens into the patient's unique perspective providing important information to industry sponsors and the FDA. Approximately 30% of trials include PROs as primary or secondary endpoints and a quarter of FDA new drug, device and biologic applications include PRO data to support labeling claims. In this paper PRO, represents any information obtained directly from the patient or their proxy, without interpretation by another individual to ascertain their health, evaluate symptoms or conditions and extends the reference of PRO, as defined by the FDA, to include other sources such as patient diaries. Consumers and clinicians consistently report that PRO data are valued, and can aide when deciding between treatment options; therefore an integral part of clinical research. However, little guidance exists for clinical research professionals (CRPs) responsible for collecting PRO data on the best practices to ensure quality data collection so that an accurate assessment of the patient's view is collected. Therefore the purpose of this work was to develop and validate a checklist to guide quality collection of PRO data. The checklist synthesizes best practices from published literature and expert opinions addressing practical and methodological challenges CRPs often encounter when collecting PRO data in research settings. PMID- 27002225 TI - Neurophysiological changes associated with implant placement. AB - OBJECTIVES: The objective of the study was to evaluate the feasibility of a standardized Quantitative Sensory Testing (QST) protocol extra- and intraoral in patients to detect and quantify sensory disturbances of the inferior alveolar nerve due to the proximity of implantation procedures to the inferior alveolar nerve canal. MATERIAL AND METHODS: Patients who had obtained an implant placement were examined by implementing a comprehensive QST protocol for extra- and intraoral use. The study included 33 patients after implant placement in the lower jaw and one patient suffering from an inferior alveolar nerve injury. Patients were tested bilaterally (chin and mucosal lower lip). RESULTS: Comparing the implanted vs. the control side, QST parameters revealed no significant neurophysiological changes in all parameters. Evaluating the development of sensory disturbances in dependency of the proximity of the implant to the inferior alveolar nerve canal, mechanical QST parameters showed no significant correlation. The mean distance of the inserted implant to the inferior nerve canal was 2.65 +/- 1.75 mm. In the case of one patient suffering from impairment of the nerve function due to implant placement, we found abnormal sensory responses to touch coexisting with numbness and temperature algesia. CONCLUSIONS: Monitoring of trigeminal nerve fiber functions by QST intra- and extraoral is feasible to evaluate oral sensory pattern after implantation procedures. Sensory disturbances of the inferior alveolar nerve were shown to be avoided by keeping an average safety zone of 2.65 mm between implant and nerve. PMID- 27002226 TI - THE EARLY BIRD CATCHES THE WORM: EARLY COST-EFFECTIVENESS ANALYSIS OF NEW MEDICAL TESTS. AB - OBJECTIVES: There is little specific guidance on performing an early cost effectiveness analysis (CEA) of medical tests. We developed a framework with general steps and applied it to two cases. METHODS: Step 1 is to narrow down the scope of analysis by defining the test's application, target population, outcome measures, and investigating current test strategies and test strategies if the new test were available. Step 2 is to collect evidence on the current test strategy. Step 3 is to develop a conceptual model of the current and new test strategies. Step 4 is to conduct the early-CEA by evaluating the potential (cost )effectiveness of the new test in clinical practice. Step 5 involves a decision about the further development of the test. RESULTS: The first case illustrated the impact of varying the test performance on the headroom (maximum possible price) of an add-on test for patients with an intermediate-risk of having rheumatoid arthritis. Analyses showed that the headroom is particularly dependent on test performance. The second case estimated the minimum performance of a confirmatory imaging test to predict individual stroke risk. Different combinations of sensitivity and specificity were found to be cost-effective; if these combinations are attainable, the medical test developer can feel more confident about the value of further development of the test. CONCLUSIONS: A well designed early-CEA methodology can improve the ability to develop (cost )effective medical tests in an efficient manner. Early-CEAs should continuously integrate insights and evidence that arise through feedback, which may convince developers to return to earlier steps. PMID- 27002227 TI - Lived experience of vulnerability from a Gypsy Roma Traveller perspective. AB - AIMS AND OBJECTIVES: To describe the lived experience of vulnerability of individuals within a Gypsy Roma Travelling community. BACKGROUND: People experience vulnerability whenever their health or usual functioning is compromised. This may increase when they enter unfamiliar surroundings, situations or relationships. One's experience of vulnerability can also be heightened through interactions between the individual and the society within which they live. Gypsy Roma Travellers are often identified as vulnerable owing to increased morbidity and mortality as well as their marginalised status within society. Yet little is known of the experiences of vulnerability by the individuals themselves. Without their stories and experiences, health professionals cannot effectively develop services that meet their needs. DESIGN: This descriptive phenomenological study sought to explore the lived experience of vulnerability in a Gypsy Roma Travelling community. METHODS: Seventeen Gypsy Roma Travellers were interviewed in 2013-2014 about their experiences of feeling vulnerable. This paper reports on the findings from the depth phase in which 13 individuals were interviewed. The interviews were conducted and analysed using Giorgi's descriptive phenomenological approach. FINDINGS: Six constituents of the phenomenon of vulnerability were identified as feeling: defined and homogenised as a group; pressurised to conform to live in a particular way; split in one's identity; a loss of one's heritage; discriminated, persecuted and threatened; and powerlessness. RELEVANCE TO CLINICAL PRACTICE: There is a wealth of evidence that Gypsy Roma Travellers experience high levels of morbidity and mortality, which has led to them being identified by health professionals and policy makers as a vulnerable community. Exploring their lived experience of vulnerability presents a different perspective regarding this concept and can help explain why they may experience poorer levels of physical and mental health. PMID- 27002229 TI - Congenital cardiac surgery fellowship training: A status update. AB - BACKGROUND: In 2007, congenital cardiac surgery became a recognized fellowship by the Accreditation Council of Graduate Medical Education (ACGME) and leads to board certification through the American Board of Thoracic Surgery (ABTS). We highlight the strengths and weaknesses in the current system of accredited training. METHODS: Data were collected from program directors, the ACGME, and the ABTS. In addition, surveys were sent to training program graduates. Topics included program accreditation status, number of fellows trained per year and per program, match results, fellow operative experience, fellow satisfaction, and post-fellowship employment status. RESULTS: There are twelve active accredited fellowship programs, and 44 trainees have completed accredited training. Each active program has trained a median of 3 fellows (range: 0-7). Operative logs were obtained from 38 of 44 (86%) graduates. The median number of total cases (minimum 75) was 136 (range: 75-236). For complex neonates (minimum 5), the median number of cases was 6 (range: 2-17). Some fellows failed to meet the minimum requirements. Thirty-six (82%) graduates responded to the survey; most were satisfied with their overall operative experience, but less with their neonatal operative experience. Of this total, 84% are currently practicing congenital cardiac surgery, and 74% secured jobs prior to completing their residency. CONCLUSIONS: Since 2007, congenital cardiac surgery training has been accredited by the ACGME. In general, the training is uniform, the operative experience is robust, and the fellows are satisfied. Although shortcomings remain, this study highlights the many strengths of the current system. PMID- 27002230 TI - Integration of protein tethering in a rapid and label-free SERS screening platform for drugs of abuse. AB - Surface enhanced Raman spectroscopy (SERS) has emerged as a promising technique for the rapid and ultrasensitive detection of molecular species such as drugs of abuse in biofluids. Yet, it remains a significant challenge to create a viable screening tool for multiple drug classes, owing to the lack of affinity of certain species for the SERS substrate and to the matrix interference in complex media. Here we report a protein tethering SERS approach, which blends plasmonic enhancement with facile drug binding, to engineer a rapid, label-free and versatile screening tool for narcotics. By exploiting the known binding attributes of human serum albumin, we determine the effective concentration of narcotics present in solution through differential enhancement of the spectral markers. In conjunction with chemometric methods, this approach not only enables unambiguous recognition of different drug classes, such as barbiturates, opiates, amphetamines and benzodiazepines, but also offers a lower limit of detection in comparison to direct SERS application. Through molecular docking simulations, we probe the mechanistic underpinnings of the protein tethering approach paving the way for narcotic detection in clinical samples in the near future. PMID- 27002228 TI - Typical 2-Cys peroxiredoxins in human parasites: Several physiological roles for a potential chemotherapy target. AB - Peroxiredoxins (Prxs) are ubiquitary proteins able to play multiple physiological roles, that include thiol-dependent peroxidase, chaperone holdase, sensor of H2O2, regulator of H2O2-dependent signal cascades, and modulator of the immune response. Prxs have been found in a great number of human pathogens, both eukaryotes and prokaryotes. Gene knock-out studies demonstrated that Prxs are essential for the survival and virulence of at least some of the pathogens tested, making these proteins potential drug targets. However, the multiplicity of roles played by Prxs constitutes an unexpected obstacle to drug development. Indeed, selective inhibitors of some of the functions of Prxs are known (namely of the peroxidase and holdase functions) and are here reported. However, it is often unclear which function is the most relevant in each pathogen, hence which one is most desirable to inhibit. Indeed there are evidences that the main physiological role of Prxs may not be the same in different parasites. We here review which functions of Prxs have been demonstrated to be relevant in different human parasites, finding that the peroxidase and chaperone activities figure prominently, whereas other known functions of Prxs have rarely, if ever, been observed in parasites, or have largely escaped detection thus far. PMID- 27002231 TI - Understanding the salinity effect on cationic polymers in inducing flocculation of the microalga Neochloris oleoabundans. AB - A mechanistic study was performed to evaluate the effect of salinity on cationic polymeric flocculants, that are used for the harvesting of microalgae. The polyacrylamide Synthofloc 5080H and the polysaccharide Chitosan were employed for the flocculation of Neochloris oleoabundans. In seawater conditions, a maximum biomass recovery of 66% was obtained with a dosage of 90mg/L Chitosan. This recovery was approximately 25% lower compared to Synthofloc 5080H reaching recoveries greater than 90% with dosages of 30mg/L. Although different recoveries were obtained with both flocculants, the polymers exhibit a similar apparent polymer length, as was evaluated from viscosity measurements. While both flocculants exhibit similar polymer lengths in increasing salinity, the zeta potential differs. This indicates that polymeric charge dominates flocculation. With increased salinity, the effectivity of cationic polymeric flocculants decreases due to a reduction in cationic charge. This mechanism was confirmed through a SEM analysis and additional experiments using flocculants with various charge densities. PMID- 27002232 TI - Complete genome of Thauera humireducens SgZ-1, a potential bacterium for environmental remediation and wastewater treatment. AB - Thauera humireducens SgZ-1(T) (KACC 16524(T)=CCTCC M2011497(T)), isolated from the anode biofilm of a microbial fuel cell, is able to grow under anaerobic conditions via the oxidation of various organic compounds coupled to the reduction of humus, Fe(III) species and nitrate. Addtionally, the strain has the ability to produce exopolysaccharide (EPS). Here, we report the complete genome sequence of T. humiruducens SgZ-1(T), which is relevant to metabolism of electron donors and acceptors for environmental remediation and wastewater treatment. PMID- 27002233 TI - Twigged streptavidin polymer as a scaffold for protein assembly. AB - Protein assemblies are an emerging tool that is finding many biological and bioengineering applications. We here propose a method for the site-specific assembly of proteins on a twigged streptavidin (SA) polymer using streptavidin as a functional scaffold. SA was genetically appended with a G tag (sortase A recognition sequence) and a Y tag (HRP recognition sequence) on its N- and C termini, respectively, to provide G-SA-Y. G-SA-Y was polymerized using HPR mediated tyrosine coupling, then fluorescent proteins were immobilized on the polymer by biotin-SA affinity and sortase A-mediated ligation. Fluorescence measurements showed that the proteins were immobilized in close proximity to each other. Hydrolyzing enzymes were also functionally assembled on the G-SA-Y polymer. The site-specific assembly of proteins on twigged SA polymer may find new applications in various biological and bioengineering fields. PMID- 27002234 TI - miRNA profiling of high, low and non-producing CHO cells during biphasic fed batch cultivation reveals process relevant targets for host cell engineering. AB - Fed-batch cultivation of recombinant Chinese hamster ovary (CHO) cell lines is one of the most widely used production modes for commercial manufacturing of recombinant protein therapeutics. Furthermore, fed-batch cultivations are often conducted as biphasic processes where the culture temperature is decreased to maximize volumetric product yields. However, it remains to be elucidated which intracellular regulatory elements actually control the observed pro-productive phenotypes. Recently, several studies have revealed microRNAs (miRNAs) to be important molecular switches of cell phenotypes. In this study, we analyzed miRNA profiles of two different recombinant CHO cell lines (high and low producer), and compared them to a non-producing CHO DG44 host cell line during fed-batch cultivation at 37 degrees C versus a temperature shift to 30 degrees C. Taking advantage of next-generation sequencing combined with cluster, correlation and differential expression analyses, we could identify 89 different miRNAs, which were differentially expressed in the different cell lines and cultivation phases. Functional validation experiments using 19 validated target miRNAs confirmed that these miRNAs indeed induced changes in process relevant phenotypes. Furthermore, computational miRNA target prediction combined with functional clustering identified putative target genes and cellular pathways, which might be regulated by these miRNAs. This study systematically identified novel target miRNAs during different phases and conditions of a biphasic fed-batch production process and functionally evaluated their potential for host cell engineering. PMID- 27002235 TI - Full chirality transfer in the synthesis of hindered tertiary boronic esters under in situ lithiation-borylation conditions. AB - Hindered tertiary neopentyl glycol boronic esters can be prepared by using in situ lithiation-borylation of enantiopure secondary benzylic carbamates at -20 degrees C with full chirality transfer. PMID- 27002237 TI - Carbon Dioxide Expanded Ethanol Extraction: Solubility and Extraction Kinetics of alpha-Pinene and cis-Verbenol. AB - In general, diffusion rates in extractions are enhanced by increasing the temperature. In this study, we instead add compressed liquid carbon dioxide to the extraction phase to accomplish faster mass transfer. The feasibility of using carbon dioxide expanded ethanol (CXE) as the extraction phase was explored, targeting two medium-polar analytes, alpha-pinene and cis-verbenol in Boswellia sacra tree resin. Hansen solubility parameters (HSP) were first calculated for the analytes and the extraction phases investigated, ethanol, CXE, and supercritical carbon dioxide (scCO2) containing ethanol as a cosolvent. Second, an extraction method with CXE as the extraction phase was optimized using a Box Behnken design, giving optimal conditions of 40 degrees C, 9.3 MPa, and 0.31 molar fraction of CO2 in ethanol. Third, the developed method was compared with a supercritical fluid extraction (SFE) method and a conventional solid liquid extraction (SLE) method, showing that CXE enables faster and more efficient extraction than both SFE and SLE. In fact, calculations based on Peleg's equation showed that the initial extraction rate of the new method is up to 10 times faster than SFE when using the highest flow rate tested, 3 mL/min. It was also discovered that it is crucial to cool the makeup solvent in the collection system for efficient analyte collection, at least in modern SFE equipment where pressure is regulated by a backpressure regulator. The use of CXE and pertinently also other CO2-expanded liquids in sample preparation shows a great potential in terms of increasing the extraction rate without elevating the temperature. PMID- 27002236 TI - Single-Molecule Investigation of Response to Oxidative DNA Damage by a Y-Family DNA Polymerase. AB - Y-family DNA polymerases are known to bypass DNA lesions in vitro and in vivo and rescue stalled DNA replication machinery. Dpo4, a well-characterized model Y family DNA polymerase, is known to catalyze translesion synthesis across a variety of DNA lesions including 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxo-dG). Our previous X-ray crystallographic, stopped-flow Forster resonance energy transfer (FRET), and computational simulation studies have revealed that Dpo4 samples a variety of global conformations as it recognizes and binds DNA. Here we employed single-molecule FRET (smFRET) techniques to investigate the kinetics and conformational dynamics of Dpo4 when it encountered 8-oxo-dG, a major oxidative lesion with high mutagenic potential. Our smFRET data indicated that Dpo4 bound the DNA substrate in multiple conformations, as suggested by three observed FRET states. An incoming correct or incorrect nucleotide affected the distribution and stability of these states with the correct nucleotide completely shifting the equilibrium toward a catalytically competent complex. Furthermore, the presence of the 8-oxo-dG lesion in the DNA stabilized both the binary and ternary complexes of Dpo4. Thus, our smFRET analysis provided a basis for the enhanced efficiency which Dpo4 is known to exhibit when replicating across from 8-oxo-dG. PMID- 27002238 TI - Instantaneous Directional Growth of Block Copolymer Nanowires During Heterogeneous Radical Polymerization (HRP). AB - Polymeric nanowires that consist of ultrahigh molecular weight block copolymers were instantaneously prepared via one-step surfactant-free heterogeneous radical polymerization (HRP). Under heterogeneous reaction and initiator-starvation conditions, the sequential copolymerization of hydrophilic and hydrophobic monomers facilitates the formation of amphiphilic ultrahigh molecular weight block copolymers, which instantaneously assemble to polymeric nanowires. As polymerization progresses, initially formed nanoparticles exhibit the directional growth due to localized repulsive forces of hydrophilic blocks and confinement of the hydrophobic blocks that adopt favorable high aspect ratio nanowire morphologies. Using one-step synthetic approach that requires only four ingredients (water as a solvent, two polymerizable monomers (one hydrophilic and one hydrophobic), and water-soluble initiator), block copolymer nanowires ~70 nm in diameter and hundreds of microns in length are instantaneously grown. For example, when 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA) and styrene (St) were copolymerized, high aspect ratio nanowires consist of ultrahigh (>10(6) g/mol) molecular weight pDMAEMA-b-St block copolymers and the presence of temperature responsive pDMAEMA blocks facilitates nanowire diameter changes as a function of temperature. These morphologies may serve as structural components of the higher order biological constructs at micro and larger length scales, ranging from single strand nanowires to engineered biomolecular networks capable of responding to diverse and transient environmental signals, and capable of dimensional changes triggered by external stimuli. PMID- 27002239 TI - Letter to: "Alim S, Ozer S, Demir S, et al. Peripapillary Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness in Children with Familial Mediterranean Fever". PMID- 27002240 TI - Quasi-Classical Trajectory Study of Atom-Diatomic Molecule Collisions in Symmetric Hyperspherical Coordinates: The F + HCl Reaction as a Test Case. AB - We investigate the reactive dynamics of the triatomic system F + HCl -> HF + Cl for total angular momentum equal zero and for different low-lying rovibrational states of the diatomic molecule. For each of the initial vibrational quantum numbers, the time evolution of the atom-diatom collision process is investigated for a wide range of impact angles and collision energies. To this purpose, the Quasi-Classical Trajectories (QCT) method was implemented in a hyperspherical configuration space. The Hamilton equations of motion are solved numerically in an intermediate effective Cartesian space to exploit the relative simplicity of this intermediate representation. Interatomic interactions are described by a London-Eyring-Polanyi-Sato potential energy surface, specifically developed for the title reaction, and the results of the QCT simulations are discussed in terms of the time-evolution of the hyperangles. The analysis of the collision dynamics using symmetric hyperspherical coordinates provides, in addition to the description in terms of a natural reaction coordinate (the hyperradius), a more striking representation of the exchange dynamics, in terms of the time-dependent probability distribution along the kinematic rotation hyperangle, and a precise distinction between direct and indirect mechanisms of the reaction. PMID- 27002241 TI - The role of endothelial cells on islet function and revascularization after islet transplantation. AB - Islet transplantation has become a widely accepted therapeutic option for selected patients with type 1 diabetes mellitus. However, in order to achieve insulin independence a great number of islets are often pooled from 2 to 4 pancreata donors. Mostly, it is due to the massive loss of islets immediately after transplant. The endothelium plays a key role in the function of native islets and during the revascularization process after islet transplantation. However, if a delayed revascularization occurs, even the remaining islets will also undergo to cell death and late graft dysfunction. Therefore, it is essential to understand how the signals are released from endothelial cells, which might regulate both differentiation of pancreatic progenitors and thereby maintenance of the graft function. New strategies to facilitate islet engraftment and a prompt revascularization could be designed to intervene and might lead to improve future results of islet transplantation. PMID- 27002242 TI - Thiol/Disulfide Homeostasis in Patients with Central Serous Chorioretinopathy. AB - PURPOSE: To evaluate dynamic thiol/disulfide homeostasis in patients with chronic central serous chorioretinopathy (cCSC). METHODS: This prospective study included 34 cCSC cases and 37 healthy individuals who were age- and sex-matched. A new colorimetric method for measuring thiol/disulfide homeostasis was used. Native thiol, total thiol/disulfide levels, disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were measured. RESULTS: The age and gender distributions were similar in both main groups. The mean duration of disease was 47.29 +/- 24 months. Native and total thiol levels were significantly lower among the cCSC group relative to the control group (p < 0.001). There was not a statistically significant difference between the cCSC and the control group in terms of disulfide levels (p = 0.492). While disulfide/native thiol and disulfide/total thiol ratios were elevated, the native thiol/total thiol ratio was decreased in the cCSC group (p = 0.017, 0.021, 0.036, respectively). Ratios obtained using plasma native thiol, total thiol, and disulfide levels differed significantly between the both groups. CONCLUSION: Disulfide/thiol ratio was significantly greater in cCSC patients relative to healthy control subjects. Our results suggest that the oxidative process is involved in the pathogenesis of the cCSC. PMID- 27002243 TI - Discovery of a Selective and Potent Inhibitor of Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Utilizing Structure-Based Drug Design. AB - The discovery of a highly potent and selective small molecule inhibitor 9 for in vitro target validation of MNK1/2 kinases is described. The aminopyrazine benzimidazole series was derived from an HTS hit and optimized by utilization of a docking model, conformation analysis, and binding pocket comparison against antitargets. PMID- 27002244 TI - Biochemical changes in black oat (avena strigosa schreb) cultivated in vineyard soils contaminated with copper. AB - Soils used for the cultivation of grapes generally have a long history of copper (Cu) based fungicide applications. As a result, these soils can accumulate Cu at levels that are capable of causing toxicity in plants that co-inhabit the vineyards. The aim of the present study was to evaluate growth parameters and oxidative stress in black oat plants grown in vineyard soils contaminated with high levels of Cu. Soil samples were collected from the Serra Gaucha and Campanha Gaucha regions, which are the main wine producing regions in the state of Rio Grande do Sul, in southern Brazil. Experiments were conducted in a greenhouse in 2009, with soils containing Cu concentrations from 2.2 to 328.7 mg kg(-1). Evaluated parameters included plant root and shoot dry matter, Cu concentration in the plant's tissues, and enzymatic and non-enzymatic biochemical parameters related to oxidative stress in the shoots of plants harvested 15 and 40 days after emergence. The Cu absorbed by plants predominantly accumulated in the roots, with little to no translocation to the shoots. Even so, oat plants showed symptoms of toxicity when grown in soils containing high Cu concentrations. The enzymatic and non-enzymatic antioxidant systems of oat plants were unable to reverse the imposed oxidative stress conditions. PMID- 27002245 TI - Metabolic syndrome in young adults with epilepsy. AB - PURPOSE: Persons with epilepsy have higher cardiovascular mortality and morbidity compared to general population and alteration of their biochemical milieu is one of the proposed mechanisms. We aimed to study the prevalence of metabolic syndrome and cardiovascular risk factors in young adults with epilepsy and the association with antiepileptic drug use. METHOD: An observational study was conducted in persons with epilepsy aged 20-49 years using antiepileptic drugs regularly for the previous three years. The subjects were examined and their blood samples were collected for fasting blood glucose and lipid profile. RESULTS: Over 18 months, 183 patients (120 males; 63 females) were recruited (mean age 32.5 +/- 8.9 years). Metabolic syndrome (MetS) by ATP III criteria was present in 54 (29.5%) subjects. People with MetS in our group had higher frequency of abdominal obesity (50.0%) and hypertriglyceridemia (55.5%) than diabetes/impaired fasting glucose (27.8%). Older age (p=0.005) and use of valproate (p=0.012) were associated with significant risk of MetS. CONCLUSION: Clinicians need to be vigilant regarding the risk of MetS while initiating treatment and following up persons with epilepsy. PMID- 27002246 TI - Movement pattern components and mastery of an object control skill with error reduced learning. AB - OBJECTIVES: This paper reports the effects of error-reduced learning on movement components and mastery of overhand throwing in children with and without intellectual disability. METHODS: Secondary data analysis was performed on two samples of children (typically developing, TD; intellectual disability, ID) who practiced overhand throwing in either an error-reduced (ER) or error-strewn (ES) condition. Movement pattern components were assessed using a sub-skill of Test of Gross Motor Development-2. RESULTS: In TD participants, ER learners displayed improved follow-through while ES learners did not. Among children with ID, ER learners displayed greater improvements of hip/shoulder rotation and follow through, than ES learners. Discriminant function analysis confirmed that changes in these components differentiated learning groups. Greater percentage of ER, compared to ES, participants progressed to mastery. CONCLUSIONS: With suppressed errors, the follow-through component of overhand throwing is likely to emerge, particularly in children with inferior abilities, and cognitive limitations. Error-reduced learning facilitates mastery. PMID- 27002247 TI - Photoferroelectric and Photopiezoelectric Properties of Organometal Halide Perovskites. AB - Piezoelectrics play a critical role in various applications. The permanent dipole associated with the molecular cations in organometal halide perovskites (OMHPs) may lead to spontaneous polarization and thus piezoelectricity. Here we explore the piezoelectric properties of OMHPs with density functional theory. We find that the piezoelectric coefficient depends sensitively on the molecular ordering and that the experimentally observed light-enhanced piezoelectricity is likely due to a nonpolar to polar structural transition. By comparing OMHPs with different atomic substitutions in the ABX3 architecture, we find that the displacement of the B-site cation contributes to nearly all of the piezoelectric response and that the competition between A-X hydrogen bond and B-X metal-halide bond in OMHPs controls the piezoelectric properties. These results highlight the potential of the OMHP architecture for designing new functional photoferroelectrics and photopiezoelectrics. PMID- 27002248 TI - Description of the Adsorption and Exciton Delocalizing Properties of p Substituted Thiophenols on CdSe Quantum Dots. AB - This work describes the quantitative characterization of the interfacial chemical and electronic structure of CdSe quantum dots (QDs) coated in one of five p substituted thiophenolates (X-TP, X = NH2, CH3O, CH3, Cl, or NO2), and the dependence of this structure on the p-substituent X. (1)H NMR spectra of mixtures of CdSe QDs and X-TPs yield the number of X-TPs bound to the surface of each QD. The binding data, in combination with the shift in the energy of the first excitonic peak of the QDs as a function of the surface coverage of X-TP and Raman and NMR analysis of the mixtures, indicate that X-TP binds to CdSe QDs in at least three modes, two modes that are responsible for exciton delocalization and a third mode that does not affect the excitonic energy. The first two modes involve displacement of OPA from the QD core, whereas the third mode forms cadmium-thiophenolate complexes that are not electronically coupled to the QD core. Fits to the data using the dual-mode binding model also yield the values of Deltar1, the average radius of exciton delocalization due to binding of the X-TP in modes 1 and 2. A 3D parametrized particle-in-a-sphere model enables the conversion of the measured value of Deltar1 for each X-TP to the height of the potential barrier that the ligand presents for tunneling of excitonic hole into the interfacial region. The height of this barrier increases from 0.3 to 0.9 eV as the substituent, X, becomes more electron-withdrawing. PMID- 27002249 TI - Sport Safety Policy Changes: Saving Lives and Protecting Athletes. PMID- 27002250 TI - Implementing Health and Safety Policy Changes at the High School Level From a Leadership Perspective. AB - CONTEXT: Although consensus statements and recommendations from professional organizations aim to reduce the incidence of injury or sudden death in sport, nothing is mandated at the high school level. This allows states the freedom to create and implement individual policies. An example of a recommended policy is heat acclimatization. Despite its efficacy in reducing sudden death related to heat stroke, very few states follow the recommended guidelines. OBJECTIVE: To retroactively examine why and how 3 states were able to facilitate the successful creation and adoption of heat-acclimatization guidelines. DESIGN: Qualitative study. SETTING: High school athletic associations in Arkansas, Georgia, and New Jersey. PATIENTS OR OTHER PARTICIPANTS: Eight men and 3 women (n = 11; 6 athletic trainers; 2 members of high school athletic associations; 2 parents; 1 physician) participated. Participant recruitment ceased when data saturation was reached. DATA COLLECTION AND ANALYSIS: All phone interviews were digitally recorded and transcribed verbatim. A grounded-theory approach guided analysis and multiple analysts and peer review were used to establish credibility. RESULTS: Each state had a different catalyst to change (student-athlete death, empirical data, proactivity). Recommendations from national governing bodies guided the policy creation. Once the decision to implement change was made, the states displayed 2 similarities: shared leadership and open communication between medical professionals and members of the high school athletic association helped overcome barriers. CONCLUSIONS: The initiating factor that spurred the change varied, yet shared leadership and communication fundamentally allowed for successful adoption of the policy. Our participants were influenced by the recommendations from national governing bodies, which align with the institutional change theory. As more states begin to examine and improve their health and safety policies, this information could serve as a valuable resource for athletic trainers in other states and for future health and safety initiatives. PMID- 27002251 TI - Variables associated with disability in male and female long-term survivors from acute myocardial infarction. Results from the MONICA/KORA Myocardial Infarction Registry. AB - Increasing attention is paid on functional limitations and disability among people with chronic diseases. However, only few studies have explored disability in persons with acute myocardial infarction (AMI). The objective of this study was to provide a description of disability and to identify determinants of disability in a population-based sample of long-term AMI survivors. The sample consisted of 1943 persons (35-85years) with AMI from the German population-based MONICA/KORA Myocardial Infarction Registry, who responded to a postal follow-up survey in 2011. Disability was assessed with the 12-item version of the World Health Organization Disability Schedule (WHODAS). Multivariate linear regression models were established in order to identify socioeconomic and clinical factors, risk factors and comorbidities which are associated with disability. The mean WHODAS score for the total sample was 7.86+/-9.38. The regression model includes 26 variables that explained 37.2% of the WHODAS variance. Most of the explained variance could be attributed to the presence of depression, female sex, joint disorders, digestive disorders, and stroke. Depression was the most important determinant of disability in both sexes. Replacement of single comorbidities by the total number of comorbidities resulted in a model with 15 variables explaining 31.9% of the WHODAS variance. Most of the variance was explained by the number of comorbidities. Further significant determinants of disability were female sex, low education level, angina pectoris, and no revascularization therapy. In AMI patients, the number of comorbidities and particularly the presence of depression are important determinants of disability and should be considered in post-AMI health care. PMID- 27002252 TI - Self-reported prenatal influenza vaccination and early childhood vaccine series completion. AB - BACKGROUND: No studies have examined associations between prenatal vaccination and childhood vaccination. Mothers who refuse influenza vaccinations during pregnancy report similar attitudes and beliefs to those who refuse vaccinations for their children. The objective of this study was to examine the association between self-reported prenatal influenza vaccination and early childhood vaccination. METHODS: A retrospective cohort study was conducted with existing surveillance data from 4022 mothers who responded to the 2009-2011 Minnesota Pregnancy Risk Assessment Monitoring System survey and child vaccination records from the Minnesota Immunization Information Connection database. The childhood vaccine series outcome included the following vaccines: diphtheria, tetanus, and pertussis; poliovirus; measles, mumps, and rubella; Haemophilus influenzae type b (Hib); hepatitis B; varicella; and pneumococcal conjugate. To evaluate the association between self-reported prenatal influenza vaccination and early childhood vaccination, unadjusted and adjusted logistic regression was used to estimate log odds for childhood vaccination status, while margins post-estimation commands were used to obtain predicted probabilities and risk differences. RESULTS: Vaccine series completion was 10.86% higher (95% confidence interval (CI) 7.33%-14.40%, adjusted and weighted model) in children of mothers who had a prenatal influenza vaccine compared to those who did not. For individual vaccines in the recommended series, risk differences ranged from 7.83% (95% CI 5.37%, 10.30%) for the Hib vaccine to 10.06% (95% CI 7.29%, 12.83%) for the hepatitis B vaccine. CONCLUSION: Self-reported prenatal influenza vaccination was associated with increased early childhood vaccination. More research is needed to confirm these results and identify potential intervention strategies. PMID- 27002253 TI - A double-risk monitoring and movement restriction policy for Ebola entry screening at airports in the United States. AB - This paper provides an alternative policy for Ebola entry screening at airports in the United States. This alternative policy considers a social contact tracing (SCT) risk level, in addition to the current health risk level used by the CDC. The performances of both policies are compared based on the scenarios that occur and the expected cost associated with implementing such policies. Sensitivity analysis is performed to identify conditions under which one policy dominates the other policy. This analysis takes into account that the alternative policy requires additional data collection, which is balanced by a more cost-effective allocation of resources. PMID- 27002254 TI - Differential association of cardiorespiratory fitness and central adiposity among US adolescents and adults: A quantile regression approach. AB - Previous studies assessing the association between cardiorespiratory fitness (CRF) and waist circumference (WC) have often restricted their evaluation to the association of CRF on average WC. Consequently, the assessment of important variations in the relationship of CRF across the WC distribution was precluded. The purpose of this study was to comprehensively evaluate the association between CRF and the distribution of WC using quantile regression. Secondary data analysis was conducted using data from the 1999-2004 NHANES. Participants (n=8260) aged 12 49years with complete data on estimated maximal oxygen consumption and WC were included. Quantile regression models were performed to assess the association between CRF and the 10th, 25th, 50th, 75th and 90th WC percentiles and were adjusted for age and race/ethnicity. For male and female adolescents with high CRF compared to low-fit counterparts, significant negative estimates (2.8 to 20.2cm and 2.3 to 11.2cm, respectively) were observed across most WC percentiles. Similarly, among male and female adults, high CRF was associated with significant reductions in WC across all percentiles (9.5 to 12.0cm and 3.7 to 9.2cm, respectively). For both populations, an increasing trend in the magnitude of the association of high CRF across the WC percentiles was observed. CRF appears to have a differential relationship across the WC distribution with the largest reductions in WC were found among high-fit individuals with the greatest amount of central adiposity (WC>=90th percentile). Additionally, this differential association highlights the significant limitations of statistical techniques used in previous analyses which focused on the center of the distribution. PMID- 27002255 TI - Cardiovascular disease documentation and counseling in electronic medical records. AB - The purpose of this paper is to explore the relationship between clinical reminders generated by electronic medical record (EMR) systems and providers giving prevention counseling to patients at-risk for cardiovascular disease (CVD). Data were extracted from the 2012 National Ambulatory Medical Care Survey (NAMCS). Results indicate that the providers routinely using clinical reminders are significantly more likely to document height and weight data to determine risk and provide the recommended counseling to patients that merit the intervention. The findings are important for policymakers and managers that have been promoting the adoption of more sophisticated EMR decision support functionalities across the care delivery spectrum. In particular, the ability to intervene prior to negative health events is an important feature of the movement to improve care quality and reduce costs. PMID- 27002256 TI - Vertebral osteomyelitis caused by non-tuberculous mycobacteria: Predisposing conditions and clinical characteristics of six cases and a review of 63 cases in the literature. AB - Background Several case series have reported on clinical and radiographic characteristics of patients with vertebral osteomyelitis (VO) caused by non tuberculous mycobacteria (NTM). However, only a few patients were included, and systematic reviews are still lacking. The aim of this study was to update and summarise the pre-disposing conditions, clinical and radiographic characteristics of such cases due to NTM. Methods In this study, a systematic review was conducted of the English-language literature from 1961-2014 to investigate the pre-disposing conditions and characteristics of cases of VO due to NTM. Also, six additional cases diagnosed in the study hospitals were described; these cases are included in an analysis of a total of 69 cases of NTM VO. Results The most common species, regardless of the presence of HIV co-infection, was M. avium Complex followed by M. xenopi. Ten cases with HIV infection had a median CD4 lymphocyte count of 320/mm(3) (range = 41-465/mm(3)) at the time of diagnosis of NTM VO. The VO in the cases with HIV infections occurred at an earlier age and more often involved the thoracic spine than in the cases without HIV infection. Pre disposing trauma or surgery was reported in 14.5% (10/69) of the cases. A variety of immunosuppressive diseases were observed in 49.3% of the patients, including the 10 with HIV infections and corticosteroids were used in 27.5% of the cases. Surgery was performed in 67.6% and improvement was reported in 80.6%. Conclusion NTM should be considered in immunocompromised patients with indolent VO without confirmation of tuberculosis. PMID- 27002257 TI - Umbilical cord and preeclampsia. AB - INTRODUCTION: Preeclampsia is associated with abnormalities in the umbilical cord in several ways: morphological, biochemical and functional. Alteration in blood vessels of the placenta, decidua and circulatory system of the fetus might be related to factors that cause preeclampsia and may be associated with alterations of the umbilical cord. OBJECTIVES: This study aimed to analyze the relationship between each type of umbilical cord abnormality and the different subtypes of hypertensive gestational disorders. METHODS: We conducted a prospective study on consecutive autopsies and its placentas, looking for abnormalities in the umbilical cord's features and their clinical associations. RESULTS: Umbilical cord abnormalities including length, diameter, insertion, entanglements, knots and coils were associated with maternal gestational hypertension. CONCLUSION: In women with gestational hypertension, umbilical cord abnormalities are associated with fetal and neonatal consequences. PMID- 27002259 TI - Increased tissue factor and thrombomodulin expression and histopathological changes in placentas of pregnancies with preeclampsia. AB - INTRODUCTION: Preeclampsia has a global frequency of 2-8% and a frequency of 10% in developing countries. In Colombia, preeclampsia causes 42% of maternal mortality. Alterations in placental homeostasis have been proposed to be involved in its pathophysiology. The aim of this study was to compare mRNA and protein levels of tissue factor (F3) and thrombomodulin (THBD) and the histopathological findings of placentas. MATERIALS AND METHODS: We studied 16 placentas from patients with preeclampsia and 19 term placentas with uncomplicated pregnancy. An expert pathologist, who was masked to the group assignment, conducted an evaluation to determine specific histological changes. Assessments of mRNA and protein levels of F3 and THBD were performed using real-time PCR and ELISA, respectively. RESULTS: Cases and controls differed in the frequency of decidual arteriopathy (p = 0.027), acute infarction (p = 0.001) and hyperplasia of the syncytiotrophoblast (p = 0.0017). Cases had increased levels of F3 mRNA (p = 0.0124) and protein (p < 0.0001) and THBD mRNA (p < 0.0001) and protein (p < 0.0001). CONCLUSION: In placenta of patients with preeclampsia, we detected abnormal expression of F3 and THBD with increased protein and mRNA levels. The role of these molecules in the pathogenesis of this disease and in alterations of hemostatic and histopathological aspects of placentas need further studying. PMID- 27002258 TI - Effect of intrauterine growth pattern on serum visfatin concentrations in full term infants at birth and at 6 months of life. AB - OBJECTIVE: Visfatin is a hormone discovered in fat cells and is directly related to diabetes. We aimed to investigate the relationship between intrauterine growth pattern and serum visfatin concentrations in full-term infants at birth and at 6 months of life. METHODS: Cord blood visfatin concentrations were assessed in 90 full-term neonates enrolled into; Group I: 30 appropriate for gestational age (AGA) neonates to healthy mothers, Group II: 30 intra-uterine growth restricted (IUGR) neonates, 19 were born to mothers with pre-eclampsia, Group III: 30 large for gestational age (LGA) neonates, 16 were infants of diabetic mothers (IDMs). Neonates were followed up at six months of age for visfatin concentrations. RESULTS: Cord blood visfatin concentrations were increased in IUGR compared to AGA group (p = 0.002). Cord blood visfatin concentrations were increased in LGA compared to AGA and IUGR groups (P < 0.001, P < 0.001). Cord blood visfatin concentrations were positively correlated to birth weight in AGA, LGA groups (r = 0.39, p = 0.045, r = 0.449, p = 0.013 respectively). Visfatin concentrations in neonates born to mothers with pre-eclampsia and IDMs were higher than in those born to mothers without pre-eclampsia and to non-diabetic mothers (p = 0.040, p = 0.002 respectively). At six months, serum visfatin concentrations decreased compared to cord blood visfatin concentrations in IUGR and LGA groups (p < 0.001). Levels in LGA were still higher than IUGR (p = 0.004). Serum visfatin concentrations were positively correlated to cord visfatin in IUGR neonates (r = 0.497, p = 0.005). CONCLUSION: Cord blood visfatin concentrations were increased in LGA and IUGR neonates. At six months, serum visfatin concentrations decreased compared to cord blood visfatin concentrations in LGA and IUGR groups, still higher in the former than the latter. PMID- 27002260 TI - A novel analytical approach to sensing fitness bracelets for a personalized perinatal care: A case report. PMID- 27002261 TI - Epsilon globin gene expression in developing human fetal tissues. AB - OBJECTIVE: The discovery of free fetal DNA in plasma of pregnant women has opened a new avenue for non-invasive prenatal diagnosis. We hypothesized that epsilon (E)-globin gene expression could serve as a positive control for the presence of fetal nucleic acid. STUDY DESIGN: We measured E-globin mRNA in human fetal tissues and compared concentrations with that measured in adult non-pregnant and pregnant samples. Total RNA was isolated from fetal marrow, liver, blood, and placenta (10-24 weeks gestation), from adult peripheral blood mononuclear cells, and from maternal plasma. RNA was reverse transcribed and quantitative polymerase chain reaction performed for E-globin expression. RESULTS: E-globin gene expression was detected in all fetal samples, was detected in plasma of pregnant women, but was negligible in non-pregnant samples. Relative E-globin gene expression was significantly greater in fetal blood compared to fetal liver, and was minimally expressed in placenta. E-globin gene expression decreased at the highest gestational ages in fetal blood, while expression was greatest at 15-19 weeks in fetal marrow. CONCLUSION: Fetal E-globin gene expression is significantly greater than adult expression and is increased in maternal plasma compared to non-pregnant samples. E-globin gene expression might serve as a positive control when determining the presence of fetal nucleic acid in total nucleic acid isolated from maternal plasma. PMID- 27002262 TI - Outcomes of peripherally inserted double lumen central catheter in very low birth weight infants. AB - OBJECTIVE: In order to evaluate safety and usefulness of peripherally inserted double lumen central catheter (PIDLCC) in very low birth weight (VLBW) infants, outcomes of VLBW infants who had PIDLCC was studied. SUBJECTIVE: Thirty-nine VLBW infants who were admitted to our NICU in 2013 were retrospectively analyzed. RESULTS: Mean birth weight and gestational age was 1042.7 gram and 28.5 weeks, respectively. Total duration of indwelling PIDLCC was 1121 days (mean 28.5+18.2 days) with 85 PIDLCCs used. Dressing at the insertion site was done twice weekly with 10% povidone iodine. Four (10.3% with mean of 48 days) infants had catheter related blood stream infection (CRBSI), with a 3.57 infection per 1000 catheter day. The mean for days of PIDLCC in 35 infants without CRBSI was 26.5 days. Organisms isolated were Staphylococcus epidermidis, Staphylococcus aureus and Staphylococcus capitis ureolytic. Our study showed significant difference in the duration of indwelling catheter (p = 0.023) and intraventricular hemorrhage (p = 0.043) between the CRBSI group and non-CRBSI group. Five (12.8%) infants had abnormal thyroid function test, in which two infants required thyroxine supplementation upon discharge. However, duration of PIDLCC and abnormal thyroid function test was not statistically significant (p = 0.218). One (2.5%) infant died (death was not related to CRBSI). There was no serious adverse effects secondary to PIDLCC. CONCLUSION: It is concluded that the use and maintenance of PIDLCC is safe for VLBW infants, but close monitoring should be observed to detect early signs of infection. PMID- 27002263 TI - Incidence and risk factors of urinary tract infection in very low birth weight infants. AB - OBJECTIVES: To describe the incidence and associated risk factors of urinary tract infection (UTI) in very low birth weight (VLBW) infants and to determine the value of diagnostic imaging studies after the first UTI episode before discharge from the neonatal intensive care unit (NICU). METHODS: VLBW infants born during 2003-2012 were reviewed for UTI. In a nested case-control study, potential risk factors of UTI were compared between infants with UTI (cases) versus birth weight and gestational age matched controls. Renal ultrasonography (USG) and voiding cystourethrography (VCUG) results were reviewed in cases. RESULTS: During the study period, 54.7% of urine culture specimens were collected by sterile methods. 3% (45/1,495) of VLBW infants met the study definition for UTI. UTI was diagnosed at mean postnatal age of 33.1+/-22.9 days. There was no significant difference in gender, ethnicity, antenatal steroid exposure, blood culture positive sepsis, ionotropic support, respiratory support and enteral feeding practices between cases and controls. Cases had a significantly higher cholestasis compared to controls (22% vs. 9% ; p = 0.03). However, cholestasis was not a significant predictor of UTI in the adjusted analysis [adjusted OR 2.38 (95% CI 0.84 to 6.80), p = 0.11]. Cases had higher central line days, parenteral nutrition days, total mechanical ventilation days, chronic lung disease, and length of stay compared to controls. Renal USG was abnormal in 37% and VCUG was abnormal in 17% of cases. CONCLUSIONS: The incidence of UTI in contemporary VLBW infants is relatively low compared to previous decades. Since no significant UTI predictors could be identified, urine culture by sterile methods is the only reliable way to exclude UTI. The majority of infants with UTI have normal renal anatomy. UTI in VLBW infants is associated with increased morbidity and length of stay. PMID- 27002264 TI - A rock and a hard place: The selective serotonin reuptake inhibitor dilemmas in addressing perinatal mood and anxiety disorders. AB - Untreated perinatal depression and anxiety increase the risk of pregnancy complications, introducing significant maternal and neonatal complications. Unfortunately, antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) is similarly associated with adverse perinatal outcomes. Providers should consider all maternal and fetal outcomes when addressing this dilemma. PMID- 27002265 TI - The impact of obesity on cervical cerclage efficacy: A systematic review of the literature. AB - BACKGROUND: Cervical cerclage is a commonly applied procedure which is used as a preventive measure against preterm births among women with a short cervix (<25mm) or with previous painless mid-trimester pregnancy losses. The purpose of the present study is to evaluate whether the presence of maternal obesity reduces the efficacy of cervical cerclage. MATERIALS AND METHODS: We searched Medline (1966 2015), Scopus (2004-2015), Popline (1974-2015) and ClinicalTrials.gov (2008-2015) along with reference lists of electronically retrieved studies. RESULTS: Three studies were included in our review which involved 606 women. Among them 210 were obese (BMI>30 kg/m2) and 47 morbidly obese (BMI >40 kg/m2). The presence of obesity among women who had a cervical cerclage due to ultrasound or history indications did not seem to affect the gestational age at delivery or the neonatal birthweight. Furthermore, according to the findings of a single study it did not seem to reduce the gestational latency period in days (normal weight group 24.3+/-3.2, overweight group 21.1+/-5.1, obese group 21.4+/-4.9 p = 0.171). CONCLUSION: According to the findings of our systematic review obesity does not influence the efficacy of cervical cerclage. However, firm results are precluded due to the small number and the methodological heterogeneity of existing studies. Further, studies are needed to corroborate our findings. PMID- 27002266 TI - Incorrect umbilical vein catheterization is associated with severe periventricular hemorrhages and mortality in extremely premature newborns. AB - OBJECTIVE: To investigate the relationship between umbilical vein catheter (UVC) placement and death in extremely premature newborns (<29 weeks gestation). STUDY DESIGN: Utilizing a retrospective, case-control study design, results for newborns that received UVC placements and died were compared with those who received UVC placements and survived (n = 719) by univariate and multiple logistic regression analyses. RESULT: Death rate was 30% in infants with low lines versus 16% in those without (p = 0.012). High UVC tip placement significantly and independently increased severe periventricular hemorrhages (p = 0.014). Severe periventricular hemorrhage increased death rates by 3-fold independent of gestational age (p < 0.001). Proper line placement significantly reduced severe periventricular hemorrhage by 2.5-fold independent of gestational age (p = 0.019). CONCLUSION: In extremely premature newborns, incorrect UVC placement is significantly associated with death through its relation to severe periventricular hemorrhage. PMID- 27002267 TI - Parental preferences regarding administration of an animal-derived versus a synthetic medication to newborn infants. AB - AIM: We examined the perceptions of parents with regard to animal-derived versus synthetic medications of comparable efficacy. We hypothesized that this issue is a concern in neonatal care and that the perceptions of parents from one geographical location would be similar to those of another. METHODS: A survey was distributed to parents of neonates admitted to a neonatal intensive care unit of a southeastern hospital. RESULTS: Of 153 parents surveyed, 150 (98%) responded. More mothers than fathers completed the surveys (113 vs. 34). Fifty-six percent of participants indicated a college or higher education; 40% had an income of $51,000/yr or higher. Thirty-four percent of parents had concerns about animal derived medications, 41% preferred a synthetic medication of equivalent efficacy, and 69% would like to be informed if a medication was animal-derived. CONCLUSION: Parents have concerns about exposing neonates to animal-derived medication and wish to be informed if an animal-derived medication is being considered. PMID- 27002268 TI - Significance of antenatal glucocorticoid exposure for pressure injury prevalence in neonates. AB - AIMS: Studies have highlighted that antenatal steroids could have an effect on neonatal skin maturation. This study examined if there was a relationship between the administration of antenatal glucocorticoids for mothers and the skin injuries in their neonates. Data from skin injury audit were extracted from the neonatal database and analyzed to determine differences in the prevalence of neonates with pressure injuries [cases] whose mothers had received antenatal steroids, compared to those without pressure injuries [control]. RESULTS: Of 247 neonates audited, 77 [31%], had documented pressure injuries, 170 [69%] had no documented injury. The median birth weight and gestation were 1400 g [IQR 893-2268 g] and 30.3 weeks [IQR 26.3-40.0 weeks] respectively. Of the neonates born less than 34 weeks, 80% were exposed to antenatal steroids and were equally distributed across patient genders. Within the 77 cases, 53 [66%] were exposed to antenatal steroids compared to controls in which 88 [53%] had not. The effect between cases and controls was not statistically significant [chi2 = 2.81, P = 0.09]. However a difference was noted between genders, as female neonates benefited from the exposure to steroids [OR = 0.317, 95% [CI 0.105-0.956], p value -0.041]. CONCLUSION: Antenatal glucocorticoids appear to be beneficial in reducing pressure injury prevalence in female neonates. PMID- 27002269 TI - Preeclampsia: Long-term effects on pediatric disability. AB - BACKGROUND: Preeclampsia affects up to 10% of pregnancies worldwide and is one of the main causes of fetal morbidity and mortality. Although it has been linked to developmental delay, its long-term effects on neurologic development in children have yet to be sufficiently quantified. OBJECTIVES: To evaluate whether preeclampsia's severity and its obstetric management correlate to the degree of disability in these infants. MATERIALS AND METHOD: This is an observational and descriptive study performed on a population of 96 women who were diagnosed with preeclampsia at Hospital General Universitario Gregorio Maranon between 2007 and 2014, and their 111 children. To evaluate the mother, we gathered data pertaining to her medical history, renal function markers, and medical management of the preeclampsia. To assess the children, we collected fetal growth measurements, acute fetal distress markers and main diagnoses at birth. We used the Pediatric Evaluation of Disability Inventory in its computerized adaptive test version (PEDI-CAT) to study performance in the relevant areas, and the TNO-AZL Preschool children Quality of Life (TAPQOL) to estimate health-related quality of life. RESULTS: PEDI-CAT percentiles were consistently lower in the social/cognitive domain than in other areas. Lower social/cognitive percentiles were associated to both lower maternal IgG levels and presence of necrotizing enterocolitis during the neonatal period. CONCLUSIONS: A connection between preeclampsia and poor social/cognitive outcomes exists that warrants further research. PMID- 27002270 TI - Scrotoschisis in a neonate with meconium peritonitis and periorchitis. AB - We present the case of an infant born with scrotoschisis and evidence of meconium periorchitis and peritonitis. A scrotal defect was noted with exposure of the left testis and spermatic cord. Meconium peritonitis and periorchitis were confirmed on operative exploration. Given the history, cystic fibrosis was suspected, but initial screening and diagnostic tests were negative. PMID- 27002271 TI - Antenatal corticosteroids in the late preterm period: A prospective cohort study. AB - OBJECTIVE: The study objective was to examine the effect of antenatal corticosteroids on the incidence of short-term neonatal morbidities in singletons born during the late preterm period. STUDY DESIGN: This was a prospective cohort study of singleton gestations at risk of imminent delivery between 34 0/7 and 36 6/7 weeks. Short-term neonatal morbidities were compared between the corticosteroid exposed and non-exposed groups. The rates of Neonatal Morbidity Composite and Any Adverse Neonatal Morbidity were then compared between the two groups. RESULTS: During the two-year study period, a total of 295 subjects were included. Of those, 74 were exposed to antenatal corticosteroids, while 221 cases constituted the non-exposed group. There was no statistically significant difference in the rate of Any Adverse Neonatal Morbidity (47.3% vs. 40.7% , p = 0.32) or the rate of Neonatal Morbidity Composite (34.4% vs. 37.8% , p = 0.59) between the two groups. Additionally, there was no statistically significant difference in the rates of neonatal intensive care unit admission, respiratory distress syndrome, transient tachypnea of the newborn, hypothermia, and need for phototherapy. CONCLUSION: Administration of antenatal corticosteroids to parturients at risk of imminent delivery during the late preterm period does not appear to reduce short-term neonatal morbidities. PMID- 27002272 TI - Fine Iron Aerosols Are Internally Mixed with Nitrate in the Urban European Atmosphere. AB - Atmospheric iron aerosol is a bioavailable essential nutrient playing a role in oceanic productivity. Using aerosol time-of-flight mass spectrometry (ATOFMS), the particle size (0.3-1.5 MUm), chemical composition and mixing state of Fe containing particles collected at two European urban sites (London and Barcelona) were characterized. Out of the six particle types accounting for the entire Fe aerosol population, that arising from long-range transport (LRT) of fine Fe containing particles (Fe-LRT, 54-82% across the two sites) was predominant. This particle type was found to be internally mixed with nitrate and not with sulfate, and likely mostly associated with urban traffic activities. This is in profound contrast with previous studies carried out in Asia, where the majority of iron containing particles are mixed with sulfate and are of coal combustion origin. Other minor fine iron aerosol sources included mineral dust (8-11%), traffic brake wear material (1-17%), shipping/oil (1-6%), biomass combustion (4-13%) and vegetative debris (1-3%). Overall, relative to anthropogenic Asian Fe-sulfate dust, anthropogenic European dust internally mixed with additional key nutrients such as nitrate is likely to play a different role in ocean global biogeochemical cycles. PMID- 27002273 TI - Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure. AB - OBJECTIVES: We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. DESIGN: Crossover design. SETTING: University animal research laboratory. SUBJECTS: Anesthetized landrace pigs. INTERVENTIONS: Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. MEASUREMENTS AND RESULTS: Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from -5.6 +/- 1.3 to -2.0 +/- 0.7 cm H2O, while concomitantly reducing pendelluft and tidal recruitment. No pendelluft was observed in the absence of spontaneous effort. CONCLUSIONS: Spontaneous effort at low positive end-expiratory pressure improved oxygenation but promoted tidal recruitment associated with pendelluft. Optimized positive end-expiratory pressure (set after lung recruitment) may reverse the harmful effects of spontaneous breathing by reducing inspiratory effort, pendelluft, and tidal recruitment. PMID- 27002274 TI - Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU. AB - OBJECTIVE: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a "banana bag" as a reflexive standard of therapy. The difficulty of diagnosing Wernicke's encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence. DATA SOURCE: MEDLINE/PubMed (1966 to June 2015) database search, the Cochrane Database of Systematic Reviews, and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to Wernicke's encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected. Articles were narratively synthesized for this review. DATA SYNTHESIS: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation as for prescribing thiamine in this setting. There is no available evidence supporting the prescription of a multivitamin. CONCLUSIONS: Based on the published literature, for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke's encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200-500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4 5 g for most adult patients), and 400-1,000 MUg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline. PMID- 27002275 TI - Serum Amyloid P Contained in Alveolar Fluid From Patients With Acute Respiratory Distress Syndrome Mediates the Inhibition of Monocyte Differentiation into Fibrocyte. AB - OBJECTIVE: Alveolar fibrocytes are monocyte-derived mesenchymal cells associated with poor prognosis in patients with acute respiratory distress syndrome. Our aims were to determine the following: 1) the ability of monocytes from acute respiratory distress syndrome patients to differentiate into fibrocytes; 2) the influence of the acute respiratory distress syndrome alveolar environment on fibrocyte differentiation; and 3) mediators involved in this modulation, focusing on serum amyloid P. DESIGN: Experimental in vitro investigation. SETTING: Two ICUs of a teaching hospital. PATIENTS: Twenty-five patients (19 mild-to-severe acute respiratory distress syndrome and six matched ventilated controls without acute respiratory distress syndrome) were enrolled. Six healthy volunteers served as non-ventilated controls. INTERVENTIONS: Peripheral blood mononuclear cells were isolated from acute respiratory distress syndrome, ventilated controls, and non-ventilated controls blood and cultured in vitro. Fibrocytes were counted at basal condition and after culture with broncho-alveolar lavage fluid. Plasma and broncho-alveolar lavage fluid serum amyloid P contents were determined by western blot and enzyme-linked immunosorbent assay. Serum amyloid P was located in normal and acute respiratory distress syndrome lung by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Acute respiratory distress syndrome peripheral blood mononuclear cells had a three-fold increased ability to differentiate into fibrocytes compared to ventilated controls or non-ventilated controls. Acute respiratory distress syndrome broncho-alveolar lavage fluid inhibited by 71% (55 94) fibrocyte differentiation compared to saline control. Ventilated controls' broncho-alveolar lavage fluid was a less potent inhibitor (51% [23-66%] of inhibition), whereas non-ventilated controls' broncho-alveolar lavage fluid had no effect on fibrocyte differentiation. Serum amyloid P concentration was decreased in plasma and dramatically increased in broncho-alveolar lavage fluid during acute respiratory distress syndrome. Alveolar serum amyloid P originated, in part, from the release of serum amyloid P associated with lung connective tissue during acute respiratory distress syndrome. Serum amyloid P depletion decreased the inhibitory effect of acute respiratory distress syndrome broncho alveolar lavage fluid by 60%, whereas serum amyloid P replenishment of serum amyloid P-depleted acute respiratory distress syndrome broncho-alveolar lavage fluid restored their full inhibitory effect. CONCLUSIONS: The presence of fibrocytes in the lung during acute respiratory distress syndrome could result in a balance between higher ability of monocytes to differentiate into fibrocytes and the inhibitory effect of the alveolar environment, mainly dependent on serum amyloid P. PMID- 27002276 TI - Risks and Benefits of Stress Ulcer Prophylaxis for Patients With Severe Sepsis. AB - OBJECTIVES: The Surviving Sepsis Campaign Guidelines recommend stress ulcer prophylaxis for patients with severe sepsis who have bleeding risks. Although sepsis has been considered as a risk factor for gastrointestinal bleeding, the effect of stress ulcer prophylaxis has not been studied in patients with severe sepsis. Furthermore, stress ulcer prophylaxis may be associated with an increased risk of hospital-acquired pneumonia or Clostridium difficile infection. The aim of this study was to investigate the risks and benefits of stress ulcer prophylaxis for patients with severe sepsis. DESIGN: Retrospective cohort study. SETTING: Five hundred twenty-six acute care hospitals in Japan. PATIENTS: A total of 70,862 patients with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-to-one propensity score matching created 15,651 pairs of patients who received stress ulcer prophylaxis within 2 days of admission and those who did not. Patient characteristics were well balanced between the two groups. No significant differences were seen between the stress ulcer prophylaxis group and the control group with regard to gastrointestinal bleeding requiring endoscopic hemostasis (0.6% vs 0.5%; p = 0.208), 30-day mortality (16.4% vs 16.9%; p = 0.249), and Clostridium difficile infection (1.4% vs 1.3%; p = 0.588). The stress ulcer prophylaxis group had a significantly higher proportion of hospital acquired pneumonia (3.9% vs 3.3%; p = 0.012) compared with the control group. CONCLUSIONS: Since the rate of gastrointestinal bleeding requiring endoscopic hemostasis is not different comparing patients with and without stress ulcer prophylaxis, and the increase in hospital-acquired pneumonia is significant, routine stress ulcer prophylaxis for patients with severe sepsis may be unnecessary. PMID- 27002277 TI - Use of the GlideScope Ranger Video Laryngoscope for Emergency Intubation in the Prehospital Setting: A Randomized Control Trial. AB - OBJECTIVES: We sought to assess whether the GlideScope Ranger video laryngoscope may be a reliable alternative to direct laryngoscopy in the prehospital setting. DESIGN: Multicenter, prospective, randomized, control trial with patient recruitment over 18 months. SETTING: Four study centers operating physician staffed rescue helicopters or ground units in Austria and Norway. PATIENTS: Adult emergency patients requiring endotracheal intubation. INTERVENTIONS: Airway management strictly following a prehospital algorithm. First and second intubation attempt employing GlideScope or direct laryngoscopy as randomized; third attempt crossover. After three failed intubation attempts, immediate use of an extraglottic airway device. MEASUREMENTS AND MAIN RESULTS: A total of 326 patients were enrolled. Success rate with the GlideScope (n = 168) versus direct laryngoscopy (n = 158) group was 61.9% (104/168) versus 96.2% (152/158), respectively (p < 0.001). The main reasons for failed GlideScope intubation were failure to advance the tube into the larynx or trachea (26/168 vs 0/158; p < 0.001) and/or impaired sight due to blood or fluids (21/168 vs 3/158; p < 0.001). When GlideScope intubation failed, direct laryngoscopy was successful in 61 of 64 patients (95.3%), whereas GlideScope enabled intubation in four of six cases (66.7%) where direct laryngoscopy failed (p = 0.055). In addition, GlideScope was prone to impaired visualization of the monitor because of ambient light (29/168; 17.3%). There was no correlation between success rates and body mass index, age, indication for airway management, or experience of the physicians, respectively. CONCLUSIONS: Video laryngoscopy is an established tool in difficult airway management, but our results shed light on the specific problems in the emergency medical service setting. Prehospital use of the GlideScope was associated with some major problems, thus resulting in a lower intubation success rate when compared with direct laryngoscopy. PMID- 27002278 TI - Irisin Increased the Number and Improved the Function of Endothelial Progenitor Cells in Diabetes Mellitus Mice. AB - The dysfunction of endothelial progenitor cells (EPCs) was found to be associated with vascular complications in diabetes mellitus (DM) patients. Previous studies found that regular exercise could improve the function of EPCs in DM patients, but the underling mechanism was unclear. Irisin, a newly identified myokine, was induced by exercise and has been demonstrated to mediate some of the positive effects of exercise. In this study, we hypothesize that irisin may have direct effects on EPC function in DM mice. These data showed for the first time that irisin increased the number of EPCs in peripheral blood of DM mice and improved the function of EPCs derived from DM mice bone marrow. The mechanism for the effect of irisin is related to the PI3K/Akt/eNOS pathway. Furthermore, irisin was demonstrated to improve endothelial repair in DM mice that received EPC transplants after carotid artery injury. The results of this study indicate a novel effect of irisin in regulating the number and function of EPCs via the PI3K/Akt/eNOS pathway, suggesting a potential for the administration of exogenous irisin as a succedaneum to improve EPC function in diabetic patients who fail to achieve such improvements through regular exercise. PMID- 27002279 TI - Does Antiarrhythmic Drug During Cardiopulmonary Resuscitation Improve the One month Survival: The SOS-KANTO 2012 Study. AB - BACKGROUND: Antiarrhythmic drugs (AAD) are often used for fatal ventricular arrhythmias during cardiopulmonary resuscitation (CPR). However, the efficacy of initial AAD administration during CPR in improving long-term prognosis remains unknown. This study retrospectively evaluated the effect of AAD administration during CPR on 1-month prognosis in the SOS-KANTO 2012 study population. METHODS AND RESULTS: Of the 16,164 out-of-hospital cardiac arrest cases, 1350 shock refractory patients were included: 747 patients not administered AAD and 603 patients administered AAD. Statistical adjustment for potential selection bias was performed using propensity score matching, yielding 1162 patients of whom 792 patients were matched (396 pairs). The primary outcome was 1-month survival. The secondary outcome was the proportion of patients with favorable neurological outcome at 1 month. Logistic regression with propensity scoring demonstrated an odds ratio (OR) for 1-month survival in the AAD group of 1.92 (P < 0.01), whereas the OR for favorable neurological outcome at 1 month was 1.44 (P = 0.26). CONCLUSIONS: Significantly greater 1-month survival was observed in the AAD group compared with the non-AAD group. However, the effect of ADD on the likelihood of a favorable neurological outcome remains unclear. The findings of the present study may indicate a requirement for future randomized controlled trials evaluating the effect of ADD administration during CPR on long-term prognosis. PMID- 27002280 TI - Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin Associated Erosions and Ulcers. AB - Aspirin for secondary cardiovascular disease prevention is well established, but treatment discontinuation, often because of gastrointestinal mucosal injury or symptoms, can lead to increased risk for cardiovascular events. Proton pump inhibitor therapy is recommended for aspirin-treated patients at gastrointestinal risk. PA32540 [enteric-coated aspirin (EC-ASA) 325 mg + immediate-release omeprazole 40 mg] was compared with EC-ASA 325 mg alone once daily for 6 months in 2 duplicate, randomized double-blind trials in gastrointestinal-risk patients taking aspirin for >=3 months for secondary prevention. In this post hoc analysis, we determined the prevalence of endoscopic upper gastrointestinal ulcers at screening and whether baseline endoscopic gastric erosions impacted subsequent ulcer development. At the screening endoscopy, 6% of subjects had upper gastrointestinal ulcers (not eligible for randomization) and 40% had gastric erosions. Conditional logistic regression modeling showed that baseline gastric erosions are significantly associated with endoscopic gastric ulcer development (OR = 2.12, 95% confidence interval, 1.26-3.57). In subjects with baseline gastric erosion, 4.2% of PA32540-treated versus 13.0% of EC-ASA-treated subjects (P = 0.001) subsequently developed endoscopic gastric ulcers. These data suggest that gastric injury predisposes to gastric ulcer development when taking EC-ASA, and exposure to immediate-release omeprazole in the presence of aspirin therapy significantly reduces the likelihood of progressing to gastric ulcers. PMID- 27002281 TI - A Tireless Giant in Vascular Research. PMID- 27002282 TI - Assessment of heavy metals bioavailability and toxicity toward Vibrio fischeri in sediment of the Huelva estuary. AB - Relationship between toxicity and bioavailable metals in sediments from the Huelva estuary and its littoral of influence was analyzed. Toxicity was assessed with Microtox(r) bioassay using a marine luminescent bacterium: Vibrio fischeri. Bioavailable metals were considered as both, acid extractable fraction of BCR procedure and the sum of exchangeable and bound to carbonates fractions of Tessier sequential extraction. A bioavailable metals index was calculated to integrate results in a single figure. Toxicity and bioavailable metals showed a similar pattern. Higher levels were found in the estuary than in the littoral (140 TU/g). In Huelva estuary, highest levels were found in the Tinto estuary (5725 TU/g), followed by the Odiel estuary (5100 TU/g) and the Padre Santo Canal (2500 TU/g). Results in this area were well over than those in nearby estuaries. Furthermore, they are similar to or even higher than those in other polluted sediments around the world. Bioavailable metal index showed a stronger correlation with acid extractable fraction of BCR (R(2) = 0.704) than that for the sum of exchangeable and bound to carbonates fractions of Tessier (R(2) = 0.661). These results suggest that bioavailable metals are an important source of sediment toxicity in the Huelva estuary and its littoral of influence, an area with one of the highest mortality risks of Spain. PMID- 27002283 TI - Variability in the substance use disorder exclusion criterion in antidepressant efficacy trials. AB - BACKGROUND: Substance use disorders are the most commonly excluded psychiatric disorder in antidepressant efficacy trials (AETs). In a recent review of AETs we noticed variability in the definition of the substance use disorder exclusion criterion. In the present report we examined in greater detail the variability in defining the substance use disorder exclusion criterion, the potential impact of this variability on excluding patients from an AET, and whether the definition of the criterion has changed in the past 20 years. METHODS: We identified 170 AETs published during the past 20 years and compared the studies published during the past 5 years (n=56) to the studies published during the 15 prior years (n=114). RESULTS: Substance abuse was more frequently used as an exclusion criterion than substance dependence. Six time frames have been used as the basis of exclusion, the most frequent being the past 12 months. The time frame had a greater impact on the number of patients who would be excluded than the abuse/dependence distinction. The definition of the substance use exclusion criterion was no different in the studies of the past 5 years compared to the prior 15 years. LIMITATIONS: A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants. CONCLUSION: Studies varied in whether abuse or dependence was the basis of exclusion, whether alcohol or illicit drugs or both were the basis of exclusion, and the time frame of the disorders' presence. We raise the question of whether the routine exclusion of patients with a substance use disorder should be reflected in a product's label. PMID- 27002284 TI - Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression. AB - BACKGROUND: Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD. METHODS: The association between CRTC1 polymorphisms and MDD was investigated in three case control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored. RESULTS: CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, beta=-1.32%, 95% CI -2.07 to -0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, beta=-0.75kg/m(2), 95% CI -1.30 to 0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study. LIMITATIONS: Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample. CONCLUSIONS: CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases. PMID- 27002285 TI - Is salivary estriol detectable in very early pregnancy? AB - OBJECTIVE: Estriol (E3) is produced by the placenta and is important for early pregnancy maintenance. In blood, E3 can be detected from the 8th week of pregnancy. Under the influence of the hypothalamic-pituitary-adrenal (HPA) axis hormone ACTH, E3 levels increase sharply after the 10th week. Although E3 can be reliably analyzed in saliva, till now information about the concentrations during the first trimester is missing. The aim of this study was to verify whether the sensitivity of a newly developed enzyme immunoassay is sufficient for the determination of salivary E3 (sE3) in very early pregnancy. METHODS: Saliva samples were collected at home, once weekly in 25 healthy pregnant women from the 6th week of gestation to the end of the first trimester. RESULTS: sE3 was detectable from the beginning of the 6th pregnancy week (M = 3.17 pg/ml, SD = 2.13). A steep significant increase between the 7th and the 8th week (p = 0.029) and again between the 10th and the 11th week (p = 0.001) was apparent. CONCLUSION: Low concentrations of sE3 can be measured during very early pregnancy and may serve as a promising, easily assessable marker for future research on the mechanisms of healthy pregnancy. PMID- 27002286 TI - Morphometrical analysis of placental functional efficiency in normotensive versus preeclamptic South African black women. AB - OBJECTIVE: To assess the umbilical cord centrality, placental morphometrics, and functional efficiency in preeclampsia. METHODS: Placental morphometry of normotensive (n = 69) and preeclamptic (n = 69) patients was evaluated. RESULTS: There was a significant reduction in mean placental surface area (p = 0.0001), length (p = 0.0001), thickness (p = 0.016), and volume (p = 0.0001) in the preeclamptic than in the normotensive groups. Umbilical cord insertion was predominantly eccentric with marginal in early (29%) and late-onset preeclampsia (16%). Placental and birth weight was lower (p = 0.0001) in preeclampsia than in the normotensive group. Placental efficiency was reduced in early-onset preeclampsia. CONCLUSION: This study demonstrates reduced placental morphometrics with impaired placental efficiency in preeclampsia. PMID- 27002288 TI - Yersinia pseudotuberculosis infection intractable by antibiotics: A rare case report. AB - INTRODUCTION: Yersinia pseudotuberculosis infection is usually cured spontaneously or with administration of antibiotics. PRESENTATION OF CASE: The patient is a twelve-year-old boy with right lower quadrant pain who had enterocolitis one month previously. Contrast-enhanced abdominal computed tomography showed a distended and edematous ileum and an intra-abdominal abscess adjacent to the mesentery with a normal appendix. The patient's general condition did not improve with antibiotics, so an ileocecectomy was performed. DISCUSSION: Yersinia pseudotuberculosis infection requiring an operation is rare. In our case, antibiotics were not effective in treating the abscess therefore surgery was required. An early diagnosis using serological studies, ultrasound of the abdomen, and fecal culture, with appropriate administration of antibiotics, may have avoided the need for surgery. Considering YP infection as a differential diagnosis is therefore important when encountering patients with enterocolitis, especially with right lower quadrant pain. Early diagnosis may assist in avoiding unnecessary operations. CONCLUSION: Diagnosis of YP infection may be missed or delayed because it is rare and difficult to detect, and must be distinguished from appendicitis. Although most YP infections are self-limiting, some rare cases will require surgery, therefore early diagnosis is essential. PMID- 27002287 TI - The effects of HIV disease and older age on laboratory-based, naturalistic, and self-perceived symptoms of prospective memory: does retrieval cue type and delay interval matter? AB - There is a rising prevalence of older HIV+ adults who are at risk of deficits in higher order neurocognitive functions and associated problems in everyday functioning. The current study applied multiprocess theory to examine the effects of HIV and aging on measures of laboratory-based, naturalistic, and self perceived symptoms of prospective memory (PM). Participants included 125 Younger (48 with HIV, age = 32 +/- 4.6 years) and 189 Older (112 with HIV, age = 56 +/- 4.9 years) adults. Controlling for global neurocognitive functioning, mood, and other demographics, older age and HIV had independent effects on long-delay time based PM in the laboratory, whereas on a naturalistic PM task older HIV- adults performed better than older HIV+ adults and younger persons. In line with the naturalistic findings, older age, but not HIV, was associated with a relative sparing of self-perceived PM failures in daily life across longer delay self-cued intervals. Findings suggest that, even in relatively younger aging cohorts, the effects of HIV and older age on PM can vary across PM delay intervals by the strategic demands of the retrieval cue type, are expressed differently in the laboratory and in daily life, and are independent of other higher order neurocognitive functions (e.g., retrospective memory). PMID- 27002289 TI - Successful laparoscopic management of duplicate gallbladder: A case report and review of literature. AB - INTRODUCTION: Gallbladder duplication is a rare congenital anomaly. Recognition of this anomaly and its various types is important since it can complicate a simple hepatobiliary surgical procedure. PRESENTATION OF CASE: We report a case of a 42 year old female who presented a 6 year history of intermittent right upper quadrant abdominal pain. Her basic blood investigations including liver function tests were normal. Pre-operative imaging revealed a cystic lesion communicating with biliary tree representing duplicated gallbladder. She subsequently underwent successful laparoscopic cholecystectomy. The operative challenges were more than those anticipated at the usual laparoscopic gallbladder procedures. After six months follow up the patient remained asymptomatic. DISCUSSION: Preoperative diagnosis plays a crucial role in planning surgery, and preventing possible biliary injuries or re-operation if accessory gallbladder has been overlooked during initial surgery. Magnetic resonance cholangiopancreatography (MRCP) is the imaging modality of choice for suspected duplicate gallbladder. Laparoscopic cholecystectomy for duplicate gallbladder is a challenging operation and should be performed with meticulous dissection of the cysto-hepatic triangle. CONCLUSION: Gallbladder anomalies should be anticipated in the presence of a cystic lesion reported around the gallbladder. The laparoscopic cholecystectomy remains feasible for intervention and should be done by an experienced laparoscopic surgeon. PMID- 27002290 TI - New technique for treating abdominal surgical site infection using CT woundgraphy and NPWT: A case report. AB - INTRODUCTION: Negative pressure wound therapy (NPWT) for abdominal surgical site infection (SSI) is becoming increasingly common, although enterocutaneous fistula (ECF) has been reported as a complication. To avoid ECF, we used computed tomography (CT) woundgraphy to evaluate the relationship between the wound and the intestine, and then safely treated the abdominal SSI with NPWT. CASE PRESENTATION: Following a laparoscopic intersphincteric resection for low rectal neuroendocrine tumor and covering ileostomy, a 59-year-old woman underwent stoma closure. Six days after surgery, we diagnosed SSI. We suspected ECF, because the wound was deep and the pus resembled enteric fluid. However, CT woundgraphy showed that the wound was separated from the abdominal cavity and the intestine by the abdominal rectus muscle. Accordingly, we performed NPWT. SSI was cured and the wound was well granulated. Twenty-three days after surgery, the patient was discharged. Eventually, the wound was completely epithelialized. DISCUSSION: Although successful NPWT has been reported for open abdominal wounds, ECF is a common complication. ECF can be prevented by separating the wound from the intestine by the omentum or muscle fascia, protecting the intestinal serosa during surgery, and applying low vacuum pressure. The relationships among the wound, the fascia, and the intestine must be evaluated before abdominal SSI treatment. One good method is CT woundgraphy, which evaluates wound extent and depth, closure of muscle fascia, and the relationship between the wound and the intestine. CONCLUSION: We report a case of CT woundgraphy before NPWT for abdominal SSI. CT woundgraphy is a good candidate for evaluating wound condition. PMID- 27002294 TI - Effects of Habitual Cigarette Smoking on Retinal Circulation in Patients With Type 2 Diabetes. AB - PURPOSE: To examine the long-term effects of cigarette smoking on retinal circulation in patients with type 2 diabetes. METHODS: Seventy-four patients with type 2 diabetes mellitus and minimal (no or mild nonproliferative) diabetic retinopathy (DR) were evaluated. These patients with type 2 diabetes were divided into three groups based on their smoking history: current smokers (n = 19), past smokers (n = 20), and never smoked (n = 35). The retinal circulatory parameters were measured with laser Doppler velocimetry and were compared among the groups. RESULTS: There were significant decreases in the retinal blood flow (RBF; 8.9 +/- 2.9 vs. 11.6 +/- 3.1 MUL/min, P = 0.009) with decreased blood velocity (V; 29.6 +/- 6.8 vs. 37.8 +/- 9.0 mm/s, P = 0.003) but no difference in the vessel diameter (D; 112.0 +/- 11.9 vs. 113.7 +/- 8.6 MUm, P = 0.57) in the current smokers compared with those who never smoked. There were no differences in the RBF, blood V, and vessel D in the past smokers compared with those who never smoked and current smokers. Multiple regression analysis showed that the creatinine level was correlated negatively with the RBF and that current smoking was significantly and independent correlated with decreased RBF. CONCLUSIONS: Our results indicated that the blood V and RBF in the retinal arterioles may decrease in patients with type 2 diabetes who are chronic smokers, suggesting that chronic smoking may be associated with decreased RBF, probably via lower blood V in the retinal arterioles in early-phase DR. PMID- 27002293 TI - A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork. AB - PURPOSE: To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. METHODS: Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. RESULTS: Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 +/- 1.9 mm Hg at fixed pump perfusion with 3 MUL/min compared to gravity perfused COgr with imputed 3.7 +/- 1.6 MUL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. CONCLUSIONS: Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID- 27002295 TI - Topical Administration of beta-1,3-Glucan to Modulate Allergic Conjunctivitis in a Murine Model. AB - PURPOSE: Recent studies on beta-1,3-glucan (BG), a cell wall component of a variety of fungi, yeasts, and bacteria, demonstrated that it affects the balance of Th1/Th2 immune responses. We therefore determined whether topical application of BG modulates ocular allergy in a murine model. METHODS: We sensitized 7- to 8 week-old BALB/c mice once with ovalbumin (OVA) and aluminum hydroxide via intraperitoneal injection. Mice were rested for 2 weeks and then challenged by instillation of OVA eye drops once daily for 13 days. We administered BG eye drops 5 minutes after OVA challenge once daily. Clinical signs were measured, the infiltration of eosinophils and mast cells into conjunctiva was assessed with flow cytometry, and the serum levels of OVA-specific IgE production and Th2 cytokines after in vitro stimulation of T cells in draining lymph nodes (LN) were determined. RESULTS: Mice treated with BG showed attenuated allergic conjunctivitis, as indicated by clinical signs and decreased production of serum OVA-specific IgE. In addition, BG treatment led to decreased infiltration of CD45+ immune cells, eosinophils, and mast cells into the conjunctiva, compared with the mice treated with vehicle alone (control mice). Administration of BG suppressed Th2 cytokine production in in vitro T-cell assays partially through the induction of interleukin (IL)-10-producing CD4 T cells in draining LNs. CONCLUSIONS: Taken together, these results suggest that BG is capable of stimulating IL-10-producing CD4+ T cells and suppressing both the Th2 response in draining LNs and conjunctival eosinophil infiltration. We therefore demonstrated the therapeutic potential of topical BG administration for allergic conjunctivitis. PMID- 27002297 TI - Structural and electronic properties of graphene nanoflakes on Au(111) and Ag(111). AB - We investigate the electronic properties of graphene nanoflakes on Ag(111) and Au(111) surfaces by means of scanning tunneling microscopy and spectroscopy as well as density functional theory calculations. Quasiparticle interference mapping allows for the clear distinction of substrate-derived contributions in scattering and those originating from graphene nanoflakes. Our analysis shows that the parabolic dispersion of Au(111) and Ag(111) surface states remains unchanged with the band minimum shifted to higher energies for the regions of the metal surface covered by graphene, reflecting a rather weak interaction between graphene and the metal surface. The analysis of graphene-related scattering on single nanoflakes yields a linear dispersion relation E(k), with a slight p doping for graphene/Au(111) and a larger n-doping for graphene/Ag(111). The obtained experimental data (doping level, band dispersions around EF, and Fermi velocity) are very well reproduced within DFT-D2/D3 approaches, which provide a detailed insight into the site-specific interaction between graphene and the underlying substrate. PMID- 27002296 TI - Elevated Fundus Autofluorescence in Monkeys Deficient in Lutein, Zeaxanthin, and Omega-3 Fatty Acids. AB - PURPOSE: We quantified fundus autofluorescence (FAF) in the nonhuman primate retina as a function of age and diets lacking lutein and zeaxanthin (L/Z) and omega-3 fatty acids. METHODS: Quantitative FAF was measured in a cross-sectional study of rhesus macaques fed a standard diet across the lifespan, and in aged rhesus macaques fed lifelong diets lacking L/Z and providing either adequate or deficient levels of omega-3 fatty acids. Macular FAF images were segmented into multiple regions of interest, and mean gray values for each region were calculated using ImageJ. The resulting FAF values were compared across ages within the standard diet animals, and among diet groups and regions. RESULTS: Fundus autofluorescence increased with age in the standard diet animals, and was highest in the perifovea. Monkeys fed L/Z-free diets with either adequate or deficient omega-3 fatty acids had significantly higher FAF overall than age matched standard diet monkeys. Examined by region, those with adequate omega-3 fatty acids had higher FAF in the fovea and superior regions, while monkeys fed the diet lacking L/Z and omega-3 fatty acids had higher FAF in all regions. CONCLUSIONS: Diets devoid of L/Z resulted in increased retinal autofluorescence, with the highest values in animals also lacking omega-3 fatty acids. The increase was equivalent to a 12- to 20-year acceleration in lipofuscin accumulation compared to animals fed a standard diet. Together these data add support for the role of these nutrients as important factors in lipofuscin accumulation, retinal aging, and progression of macular disease. PMID- 27002298 TI - A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 2 and 4 Weeks of Twice-Daily Ocular Trabodenoson in Adults with Ocular Hypertension or Primary Open-Angle Glaucoma. AB - PURPOSE: To evaluate the safety and ocular hypotensive efficacy of 4 trabodenoson doses administered twice daily over 14 or 28 days in subjects with ocular hypertension or primary open-angle glaucoma (POAG). METHODS: In this multicenter, randomized, double-masked, placebo-controlled, dose-escalation Phase 2 study, patients received unilateral topical twice-daily trabodenoson (50, 100, or 200 mcg) or placebo for 14 days, or 500 mcg trabodenoson or placebo for 28 days. Ocular and systemic safety and tolerability were assessed by examinations, clinical and laboratory studies. Intraocular pressure (IOP) was assessed using Goldmann tonometry. RESULTS: Trabodenoson was well tolerated; no clinically meaningful ocular or systemic side effects were identified. Trabodenoson produced a dose-dependent IOP reduction. IOP reductions in the 500 mcg group were significantly greater than placebo at all time points at Day 28. Mean IOP reductions from diurnal baseline ranged from -3.5 to -5.0 mmHg with a mean change of -4.1 mmHg in the 500 mcg group compared -1.0 to -2.5 mmHg with a mean change of -1.6 mmHg for the placebo group, and the Day 28 drop was significantly greater than at Day 14 (P = 0.0163) indicating improvement in IOP lowering with longer treatment time. IOP remained significantly reduced 24 h after the final 500 mcg dose (P = 0.048). CONCLUSION: Twice-daily ocular doses of trabodenoson, from 50 to 500 mcg, were well tolerated and showed a dose-related decrease in IOP that was statistically significant and clinically relevant at 500 mcg in patients with ocular hypertension or POAG. PMID- 27002301 TI - Polycystic ovary syndrome and vitiligo: simple association or tight connection? PMID- 27002299 TI - Loading rates during walking in adolescents with type II osteonecrosis secondary to pelvic osteotomy. AB - Although Pemberton osteotomy has shown a high success rate even in older children, the occurrence of osteonecrosis (ON) remains one of the most severe complications, leading to premature osteoarthritis. Patients with type II ON are characterized by a valgus deformity of the proximal femur with altered musculoskeletal conditions, affecting the ability to attenuate or sustain the impulsive loading from the ground reaction force. It remains unclear whether these conditions also predispose these patients to harmful impulsive loadings. This study aimed to bridge the gap by measuring the loading rates in the lower limbs during level walking in adolescents who were treated during their infancy for unilateral developmental dysplasia of the hip by a pelvic osteotomy, with or without having developed type II ON. Patients with type II ON were found to display increased loading rates, not only at both the affected and unaffected hip, but also at other joints of the affected limb during level walking when compared to patients without ON changes (p < 0.05). These results suggest that patients with type II ON may be at a higher risk of developing premature hip osteoarthritis that is closely related to abnormal loading rates during gait. It is suggested that regular monitoring of joint loading rates in patients with type II ON is necessary for early identification of damaging loadings, and that early intervention aimed at reducing these loadings should be considered. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2199-2206, 2016. PMID- 27002302 TI - Ataxia telangiectasia, Menkes kinky hair disease and neurocutaneous melanosis. AB - This article explores three neurocutaneous syndromes (NCSs), i.e. genetic disorders producing developmental abnormalities of the skin and an increased risk of neurological complications. In this review, different aspects of ataxia telangiectasia, Menkes kinky hair disease and neurocutaneous melanosis are examined: clinical features, genetic defect, mutation spectrum, pathogenesis, and neurobiological basis; indications for clinical practice are also provided to the readers. The aim of this review is to stress the importance of cooperation among dermatologists, neurologists and psychiatrists, in order to provide patients suffering from these diseases with timely diagnosis and targeted treatments. PMID- 27002303 TI - Detection of influenza virus using peroxidase-mimic of gold nanoparticles. AB - A modified enzyme-linked immunosorbent assay (ELISA) with nanomaterials is an effective and powerful method to amplify the signal and reduce the cost of detecting and measuring trace biomarkers or proteins. In this study, an ultra sensitive colorimetric immunoassay was designed, and its ability to detect influenza viruses using positively charged gold nanoparticles ((+)Au NPs) was assessed as a possible role for peroxidase-mimic inorganic enzymes. This method detected influenza virus A (H1N1) with a linear range up to 10 pg mL(-1) and clinically isolated influenza virus A (H3N2) up to 10 plaque forming units (PFU) mL(-1) , where its sensitivity improved to 500-fold higher than that of commercial virus kits. The sensitivity of this proposed method was not declined even though in complex biological media in compared to conventional ELISA. These results revealed that the (+)AuNP-based colorimetric immunoassay could be suitable for lab-on-a-chip device and open new opportunities for clinical protein diagnostics. Biotechnol. Bioeng. 2016;113: 2298-2303. (c) 2016 Wiley Periodicals, Inc. PMID- 27002304 TI - Longitudinal Changes and Seasonal Variation in Body Composition in Professional Australian Football Players. AB - PURPOSE: To compare development and variations in body composition of early-, mid , and late-career professional Australian Football (AF) players over 3 successive seasons. METHODS: Regional and total-body composition (body mass [BM], fat mass [FM], fat-free soft-tissue mass [FFSTM], and bone mineral content [BMC]) were assessed 4 times, at the same time of each season-start preseason (SP), end preseason (EP), midseason (MS), and end season (ES)-from 22 professional AF players using pencil-beam dual-energy X-ray absorptiometry. Nutritional intake for each player was evaluated concomitantly using 3-d food diaries. Players were classified according to their age at the beginning of the observational period as either early- (<21 y, n = 8), mid- (21 to 25 y, n = 9), or late- (>25 y, n = 5) career athletes. RESULTS: Early-career players had lower FFSTM, BMC, and BM than mid- and late-career throughout. FM and %FM had greatest variability, particularly in the early-career players. FM reduced and FFSTM increased from SP to EP, while FM and FFSTM decreased from EP to MS. FM increased and FFSTM decreased from MS to ES, while FM and FFSTM increased during the off-season. CONCLUSIONS: Early-career players may benefit from greater emphasis on specific nutrition and resistance-training strategies aimed at increasing FFSTM, while all players should balance training and diet toward the end of season to minimize increases in FM. PMID- 27002305 TI - Serological Survey of West Nile Virus in Domestic Animals from Northwest Senegal. AB - In Africa, infection with West Nile virus (WNV) is frequent but almost always asymptomatic in humans and equids. The aim of this study was to identify whether any other domestic animal living in the same enzootic locality may be the sentinel of WNV circulation. In northwest Senegal, blood samples were collected from 283 adult domestic animals (136 sheep, 64 horses, 29 donkeys, 29 goats, 14 cattle, and 11 dogs), in three localities near Keur Momar Sarr. Each serum was tested for WNV immunoglobulin G using enzyme-linked immunosorbent assay. The prevalence among donkeys, horses, dogs, goats, cattle, and sheep was 86.2%, 68.7%, 27.3%, 6.9%, 0%, and 0%, respectively. This survey confirms that equids and dogs could be the best sentinel animals for surveillance of WNV. The ruminants do not play a role in WNV epidemiology. PMID- 27002307 TI - Human papillomavirus integration pattern and demographic, clinical, and survival characteristics of patients with oropharyngeal squamous cell carcinoma. AB - BACKGROUND: In human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC), reported rates of HPV integration into the host genome vary. Among patients with oropharyngeal SCC, we determined differences in demographic, clinical, and survival characteristics between those with integrated and episomal HPV. METHODS: The analysis included patients with newly diagnosed oropharyngeal SCC presenting to one institution during 1996 to 2011. HPV-positive samples were classified according to HPV physical state as integrated, episomal, or mixed. Overall, progression-free, and disease-specific survival, distant metastasis rate, and second primary malignancy rate were calculated. RESULTS: Among 307 patients, 179 had HPV-positive tumors. Of these, 22 (12%) had episomal, 42 (24%) had integrated, and 115 (64%) had mixed HPV. Among the 3 subgroups, there were no significant differences in demographic, clinical, or survival characteristics. CONCLUSION: The majority of HPV-positive oropharyngeal SCCs have either integrated or both episomal and integrated HPV with no significant differences in survival among the groups. (c) 2016 Wiley Periodicals, Inc. Head Neck 38:1139 1144, 2016. PMID- 27002306 TI - Y-632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein, and exerts antitumor activity in vitro and in vivo. AB - Heat shock protein 90 (Hsp90) stabilizes a variety of proteins required for cancer cell survival and has been identified as a promising drug target for cancer treatment. To date, several Hsp90 inhibitors have entered into clinical trials, but none has been approved for cancer therapy yet. Thus, exploring new Hsp90 inhibitors with novel mechanisms of action is urgent. In the present study, we show that Y-632, a novel pyrimidine derivative, inhibited Hsp90 in a different way from the conventional Hsp90 inhibitor geldanamycin. Y-632 induced degradation of diverse Hsp90 client proteins through the ubiquitin-proteasome pathway, as geldanamycin did; however, it neither directly bound to Hsp90 nor inhibited Hsp90 ATPase activity. Y-632 inhibited Hsp90 function mainly through inducing intracellular thiol oxidation, which led to disruption of the Hsp90-Hsp70/Hsp90 organizing protein complex and further induced cell adhesion inhibition, G0 /G1 cell cycle arrest, and apoptosis. Moreover, Y-632 efficiently overcame imatinib resistance mediated by Bcr-Abl point mutations both in vitro and in vivo. We believe that Y-632, acting as a novel small-molecule inhibitor of the Hsp90 Hsp70/Hsp90 organizing protein complex, has great potential to be a promising Hsp90 inhibitor for cancer therapy, such as for imatinib-resistant leukemia. PMID- 27002308 TI - The Dam Bursts for Porous Liquids. AB - In 2007 the idea was put forward that, through careful molecular design, it should be possible to synthesize liquids which contain permanent, well-defined molecule-sized cavities (pores). Such "porous liquids" could be a kind of liquid zeolite, or liquid MOF (metal-organic framework), exhibiting the size and shape selective sorption (or dissolution) associated with microporous solids as well as the fluidity of liquids - a new and potentially useful combination of properties. However, these materials remained essentially hypothetical until recently. In 2014 and 2015 three papers were published which describe convincing examples of porous liquids, and studies have shown that they do exhibit some remarkable properties, such as very fast gas diffusion and high gas solubilities. The examples reported so far are almost certainly only the tip of the iceberg. Now that porous liquids are 'real', a new area of materials science may open up, with clear potential for long-term applications in chemical processes. PMID- 27002309 TI - Wide bandgap mesoporous hematite nanowire bundles as a sensitive and rapid response ethanol sensor. AB - In this study, alpha-Fe2O3 nanowires were synthesized using mesoporous SBA-15 silica as the hard templates with the nanocasting method, and then mesoporous alpha-Fe2O3 nanowire bundles (NWBs) were separated from the well-dispersed alpha Fe2O3 nanowires (NWs) by the centrifugation technique. Both samples were characterized by x-ray diffraction, transmission electron microscopy (TEM), nitrogen adsorption/desorption isotherm and UV-vis spectra. All results indicated that the alpha-Fe2O3 NWBs with mesoporous structure presented a higher BET surface area (95 m(2) g(-1)) and wider bandgap (2.08 eV) than those of alpha Fe2O3 NWs (32 m(2) g(-1) and 1.91 eV). The bandgap of alpha-Fe2O3 NWBs was in accordance with the bulk alpha-Fe2O3, while the BET surface area was much higher. The results from the gas-sensing measurement revealed that the alpha-Fe2O3 NWBs based gas sensor exhibited a high sensitivity of 21.7, fast response-recovery of 7.5 s and 1 s, and good selectivity to ethanol at 340 degrees C. The sensitivity (21.7) for ethanol of alpha-Fe2O3 NWBs was much better than that of the alpha Fe2O3 NWs (12.2), which should be attributed to the higher BET surface area and wider bandgap of alpha-Fe2O3 NWBs. PMID- 27002310 TI - High desolvation temperature facilitates the ESI-source H/D exchange at non labile sites of hydroxybenzoic acids and aromatic amino acids. AB - Hydrogen/deuterium exchange coupled with high-resolution mass spectrometry has become a powerful analytical approach for structural investigations of complex organic matrices. Here we report the feasibility of the site-specific H/D exchange of non-labile hydrogens directly in the electrospray ionization (ESI) source, which was facilitated by an increase in the desolvation temperature from 200 degrees C up to 400 degrees C. We have found that the exchanges at non labile sites were observed only for the model compounds capable of keto-enol tautomeric transformations (e.g., 2,3-, 2,4-dihydroxybenzoic acids, gallic acid, DOPA), and only when water was used as a solvent. We hypothesized that the detected additional exchanges were induced by the presence of hydroxyls in the sprayed water droplets generated in the negative ESI mode. It was indicative of the exchange reactions taking place in the sprayed droplets rather than in the gas phase. To support this hypothesis, the H/D exchange experiments were run in deuterated water under base-catalyzed conditions for three model compounds, which showed the most intensive exchanges in the MS experiments: DOPA, 2,4-DHB, and 5 acetylsalicylic acid. (2)H NMR spectroscopy has confirmed keto-enolic transformations of the model compounds leading to the specific labeling of the corresponding non-labile sites. We believe that the proposed technique will be useful for structural investigations of natural complex mixtures (e.g. proteins, humic substances) using site-specific H/D exchange. PMID- 27002311 TI - HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction. AB - Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABO compatibility, and donor size. HLA matching is not routinely considered; however, the presence or later development of anti-HLA antibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLA incompatibility was a significant predictor of CLAD. One hundred seventy-five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post-LTx monitoring was continued for at least 12 months, or until patient death. HLA typing was performed by sequence-based typing and Luminex sequence-specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA-DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD (hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71-8.29 p < 0.001). When bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) were analyzed independently, HLA-DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS (HR 8.3, 95% CI: 2.46-27.97 p < 0.001) but not BOS (HR 1.92, 95% CI: 0.64-5.72, p = 0.237). HLA-A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor-recipient immune compatibility in LTx. PMID- 27002312 TI - Platelet closure time in anesthetized Greyhounds with hemorrhagic shock treated with hydroxyethyl starch 130/0.4 or 0.9% sodium chloride infusions. AB - OBJECTIVE: To measure platelet closure time (PCT) in dogs during controlled hemorrhagic shock and after fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 or 0.9% sodium chloride. DESIGN: Experimental interventional study. SETTING: University veterinary teaching hospital. ANIMALS: Eleven healthy Greyhounds. INTERVENTIONS: Dogs were anesthetized and had 48 mL/kg of blood removed to induce hemorrhagic shock. Dogs received 20 mL/kg of HES 130/0.4 (n = 6) or 80 mL/kg of 0.9% sodium chloride (NaCl; n = 5) intravenously over 20 minutes. PCT was measured using the Platelet Function Analyzer-100 with collagen and adenosine-diphosphate cartridges at: T0 = 60 minutes after induction of anesthesia prior to hemorrhage, T1 = during hemorrhagic shock, and T2 = 40 minutes after completion of fluid bolus. Packed cell volume and platelet count were concurrently measured. MEASUREMENT AND MAIN RESULTS: Hemorrhagic shock did not significantly change PCT, with no difference between T0 and T1. Both the HES 130/0.4 and 0.9% NaCl group had a significantly increased mean PCT at T2 of 91.4 seconds (95% CI 69.3-113.4) and 95.5 seconds (95% CI 78.2-112.8), respectively, compared to T1. The magnitude of change was significantly greater for the 0.9% NaCl group than the HES 130/0.4 group. There was no difference in the magnitude of change in PCV and platelet count between the 2 groups. The PCV and platelet count were >25% and >100,000/MUL, respectively, in all dogs, except for dogs in the HES 130/0.4 group at T2 where platelet counts were <100,000/MUL. CONCLUSION: Controlled hemorrhagic shock in Greyhounds under anesthesia did not cause a significant change in PCT. Both HES 130/0.4 and 0.9% NaCl administration after induction of shock increased PCT. These results do not support that HES 130/0.4 causes relevant platelet dysfunction beyond hemodilution. PMID- 27002313 TI - Phenolic Profiles and Contribution of Individual Compounds to Antioxidant Activity of Apple Powders. AB - Apples (Malus domestica L.) are the most common source of phenolic compounds in northern European diet. Besides pectins, dietary fibers, vitamins, and oligosaccharides they contain phenolic compounds of different classes. Apple powders are convenient functional forms retaining significant amounts of phenolic antioxidants. In this study reducing and radical scavenging profiles of freeze dried powders of "Aldas,? "Auksis,? "Connel Red,? "Ligol,? "Lodel,? and "Rajka? were determined and phenolic constituents were identified using ultra high performance liquid chromatography coupled to quadrupole and time-of-flight mass spectrometers. A negative ionization mode was applied and seventeen compounds: phenolic acids (coumaroylquinic, chlorogenic), flavonoids (quercetin derivatives), and procyanidin derivatives (B1, B2, and C1) were identified in all tested apple samples. Total values of Trolox equivalents varied from 7.72 +/- 0.32 up to 20.02 +/- 0.52 and from 11.10 +/- 0.57 up to 21.42 +/- 0.75 MUmol/g of dry weight of apple powder in FRAP (ferric reducing antioxidant power) and ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) postcolumn assays, respectively. The greatest Trolox equivalent values were determined for apples of "Aldas? cultivar. Chlorogenic acid and procyanidin C1 were the most significant contributors to total reducing and radical scavenging activity in all apple cultivars tested, therefore they could be considered as markers of antioxidant activity. PMID- 27002314 TI - Reliability and Normative Data for the Dynamic Visual Acuity Test for Vestibular Screening. AB - HYPOTHESIS: The purpose of this study was to determine reliability of computerized dynamic visual acuity (DVA) testing and to determine reference values for younger and older adults. BACKGROUND: A primary function of the vestibular system is to maintain gaze stability during head motion. The DVA test quantifies gaze stabilization with the head moving versus stationary. Commercially available computerized systems allow clinicians to incorporate DVA into their assessment; however, information regarding reliability and normative values of these systems is sparse. METHODS: Forty-six healthy adults, grouped by age, with normal vestibular function were recruited. Each participant completed computerized DVA testing including static visual acuity, minimum perception time, and DVA using the NeuroCom inVision System. Testing was performed by two examiners in the same session and then repeated at a follow-up session 3 to 14 days later. Intraclass correlation coefficients (ICCs) were used to determine inter-rater and test-retest reliability. RESULTS: ICCs for inter-rater reliability ranged from 0.323 to 0.937 and from 0.434 to 0.909 for horizontal and vertical head movements, respectively. ICCs for test-retest reliability ranged from 0.154 to 0.856 and from 0.377 to 0.9062 for horizontal and vertical head movements, respectively. Overall, raw scores (left/right DVA and up/down DVA) were more reliable than DVA loss scores. CONCLUSION: Reliability of a commercially available DVA system has poor-to-fair reliability for DVA loss scores. The use of a convergence paradigm and not incorporating the forced choice paradigm may contribute to poor reliability. PMID- 27002315 TI - Highly diverse posaviruses in swine faeces are aquatic in origin. AB - Posaviruses are a group of highly divergent viruses identified in swine faeces that are distantly related to other members of the order Picornavirales. Eighteen posavirus genomes were assembled from 10 out of 25 (40 %) faecal-swab pools collected from healthy adult swine. Phylogenetic analysis of the conserved RNA dependent RNA polymerase (Pol) domain found that posaviruses form a large, highly diverse, monophyletic clade, which includes similar viruses identified in human (husavirus) and fish (fisavirus) faeces or intestinal contents, respectively. Quantitative reverse transcription PCR analysis of water samples collected from commercial swine barns identified four out of 19 (21 %) samples were positive using a 5'-nuclease assay targeting the Pol region of posavirus 1. ICPD (immunoprecipitation coupled to PCR detection) assays to explore serological evidence of posavirus infection found only a single positive sample, suggesting posaviruses do not commonly infect swine, and together these results suggests a likely aquatic host. PMID- 27002316 TI - Inhibition of MMP activity can restore NKG2D ligand expression in gastric cancer, leading to improved NK cell susceptibility. AB - BACKGROUND AND METHODS: Natural killer (NK) cells can react with tumor cells through the balance of inhibitory and stimulatory signals between NK cell surface receptors and their ligands, such as MHC class I chain-related A (MICA), MHC class I chain-related B (MICB), and several UL16-binding proteins (ULBPs). In the present study, we evaluated the relationship between NKG2D ligand expression and matrix metalloproteinase (MMP) activity in in vitro culture systems of a panel of gastric cancer cell lines (n = 10) and clinical samples (n = 102). RESULTS: First, the surface expression of NK group 2 member D (NKG2D) ligands (MICA, MICB, ULBP-2, and ULBP-3) on tumor cells was markedly downregulated on in vitro culture, in parallel to the upregulation of MMPs analyzed by gelatin zymography and gene expression microarray, whereas the transcript levels of NKG2D ligands remained unchanged on in vitro culture. Second, MMP-specific inhibitors could restore the downregulated expression of NKG2D ligands and functionally improve susceptibilities to NK cells in vitro. Third, the production of soluble NKG2D ligands was increased on in vitro culture and was inhibited by MMP-specific inhibitors. Finally, there was a significant inverse correlation between MMP-9 expression and NKG2D ligand expression as analyzed by immunohistochemistry in clinical tumor samples. CONCLUSION: The present study is a comprehensive study demonstrating that upregulation of MMP activity can induce a downregulation of expression of NKG2D ligands in gastric cancer cells, leading to lower-level susceptibility to NK cells. PMID- 27002317 TI - Addressing Medicaid Expansion from the Perspective of Patient Experience in Hospitals. AB - BACKGROUND: More Medicaid holders are entering the healthcare system consequential to Medicaid expansion. Their experience has financial consequences for hospitals and crucial implications for the provision of patient-centered care. This study examined how the hospital characteristics, especially the rates of Medicaid coverage and racial/ethnic minorities, impact the quality of inpatient care. METHODS: Using data for years 2009-2011 for 870 observations of California hospitals, and data collected from patients via the Hospital Consumer Assessment of Healthcare Providers and Systems survey coupled with data from the Healthcare Cost and Utilization Project and American Hospital Association Annual Survey, we used a generalized estimating equation approach to evaluate patients' experience with hospital care. Our multivariate model includes a comprehensive set of characteristics capturing market, structural, process, and patient demographics associated with the patient's hospital stay. RESULTS: The findings indicate that high concentrations of Medicaid patients in the hospital negatively impact the perceived patient experience. In addition, all things being equal, hospitals with higher concentrations of Hispanic, Black, and Asian patients received lower patient satisfaction results on 28 of the 30 regression coefficients capturing patient satisfaction, with 22 of the 30 negative coefficients statistically significant. CONCLUSIONS: Hospitals serving higher concentrations of Medicaid patients and more racial/ethnic diverse patients experienced a less satisfactory patient experience than patients utilizing other payers or patients who were White. Our research magnifies the challenge for addressing the disparities that exist in healthcare. Further research is called for clarifying the underlying reasons for these disparities and the optimal strategies for addressing these problems. PMID- 27002318 TI - Understanding the Patient Perspective of Seizure Severity in Epilepsy: Development of a Conceptual Model. AB - PURPOSE: For patients with uncontrolled epilepsy, the severity and postictal sequelae of seizures might be more impactful than their frequency. Seizure severity is often assessed using patient-reported outcome (PRO) instruments; however, evidence of content validity for existing instruments is lacking. Our aim was to understand the real-life experiences of patients with uncontrolled epilepsy. METHODS: A preliminary conceptual model was developed. The model was refined through (1) a targeted literature review of qualitative research on seizure severity; (2) interviews with four clinical epilepsy experts to evaluate identified concepts; and (3) qualitative interviews with patients with uncontrolled epilepsy, gathering descriptions of symptoms and impacts of epilepsy, focusing on how patients experience and describe "seizure severity." Findings were summarized in a final conceptual model of seizure severity in epilepsy. RESULTS: Twenty-five patients (12 who experienced primary generalized tonic-clonic seizures and 13 who experienced partial-onset seizures) expressed 42 different symptoms and 26 different impacts related to seizures. The final conceptual model contained a wide range of concepts related to seizure frequency, symptoms, and duration. CONCLUSION: Our model identified several new concepts that characterize the patient experience of seizure severity. A seizure severity PRO instrument should cover a wide range of seizure symptoms alongside frequency and duration of seizures. This qualitative work reinforces the notion that measuring seizure frequency is insufficient and that seizure severity is important in defining the patient's experience of epilepsy. This model could be used to assess the content validity of existing PRO instruments, or could support the development of a new one. PMID- 27002319 TI - A comprehensive 6-year retrospective study on medialisation thyroplasty in the Indian population. AB - The purpose of this paper is to describe a series of patients who have undergone medialisation thyroplasty (with or without arytenoid adduction) at our centre with respect to demographics, aetiology for unilateral vocal fold paralysis, pre- and postoperative maximum phonation time, amount of anterior and posterior medialisation required and complications. A comparative analysis with international studies was also performed. A retrospective analysis was performed on 67 patients, who underwent medialisation thyroplasty at our centre from August 2008 to August 2014. All the medialisation thyroplasty were performed using Netterville's technique. The average anterior medialisation needed was 2.25 mm (SD 1.05 mm) while the average posterior medialisation needed was 6.75 mm (SD 1.79 mm). Our study is the first to determine the amount of anterior and posterior medialisation needed in the Indian population. Mean anterior and posterior medialisation required was found to be the same, regardless of the age, gender of the patient and side of surgery. PMID- 27002320 TI - A Unifying Concept of Uveal Pigment Cell Distribution and Dissemination Based on an Animal Model: Insights into Ocular Melanogenesis. AB - Pigmented cells are derived from neural crest cells, which migrate along the peripheral nerve sheets into their specific final region. During their migration, cells progressively acquire pigment-producing capabilities, maturation, and the shape of melanocytes. These insights, along with specific clinical characteristics of melanocytic nevi, have led to new concepts of cutaneous, periocular, and iris nevogenesis. To further elucidate the specific ocular embryogenic melanoblast distribution and dissemination - that could explain the distinct distribution of uveal melanocytic neoplasms - we investigated the ocular pigmentation of dogs affected by a specific mutation called Merle, which results in either pigment- (wild type) or non-pigment- (mutated type) producing cells. Based on our observations, we propose a unifying concept of uveal pigment cell distribution and dissemination, which postulates melanoblast migration and maturation following the trigeminal V1 branch and, later, their entrance into the eye along the ciliary nerves and their finest iris branches. Our concept provides an explanation not only for the specific distribution of ocular melanocytic lesions, including uveal and iris nevi, but also for the different locations depending on the metastatic potential of the ocular melanoma. Though speculative, the higher metastatic potential of posterior uveal melanomas compared to iris melanomas may be related to a less differentiated stage in the maturation of migrating melanocytes in the posterior segment compared to the anterior segment of the eye. However, there is a need of further studies focusing on cell differentiation markers of melanocytes at different locations in the eye. PMID- 27002321 TI - Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo. AB - BACKGROUND: Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo. METHODS: Cryo transmission electron microscopy (TEM) examined ApoA-II's influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT) by fluorescence imaging. Scavenger receptor class B type 1(SR-B1) expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively. RESULTS: ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A II) and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6) and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold. CONCLUSION: Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities. PMID- 27002322 TI - Compassionate and Proactive Interventions by Health Workers in the United Kingdom: A Better Approach to Prevent and Respond to Female Genital Mutilation? AB - Amasanti and colleagues consider female genital mutilation in the UK, how overly intrusive efforts to help might make the problem worse, and how best to move forwards. PMID- 27002323 TI - The Gastropod Menace: Slugs on Brassica Plants Affect Caterpillar Survival through Consumption and Interference with Parasitoid Attraction. AB - Terrestrial molluscs and insect herbivores play a major role as plant consumers in a number of ecosystems, but their direct and indirect interactions have hardly been explored. The omnivorous nature of slugs makes them potential disrupters of predator-prey relationships, as a direct threat to small insects and through indirect, plant-mediated effects. Here, we examined the effects of the presence of two species of slugs, Arion rufus (native) and A. vulgaris (invasive) on the survivorship of young Pieris brassicae caterpillars when feeding on Brassica rapa plants, and on plant attractiveness to the main natural enemy of P. brassicae, the parasitoid Cotesia glomerata. In two separate predation experiments, caterpillar mortality was significantly higher on plants co-infested with A. rufus or A. vulgaris. Moreover, caterpillar mortality correlated positively with slug mass and leaf consumption by A. vulgaris. At the third trophic level, plants infested with slugs and plants co-infested with slugs and caterpillars were far less attractive to parasitoids than plants damaged by caterpillars only, independently of slug species. Chemical analyses confirmed that volatile emissions, which provide foraging cues for parasitoids, were strongly reduced in co-infested plants. Our study shows that the presence of slugs has the potential to affect insect populations, directly via consumptive effects, and indirectly via changes in plant volatiles that result in a reduced attraction of natural enemies. The fitness cost for P. brassicae imposed by increased mortality in presence of slugs may be counterbalanced by the benefit of escaping its parasitoids. PMID- 27002324 TI - High Prevalence of Post-Traumatic Stress Symptoms in Relation to Social Factors in Affected Population One Year after the Fukushima Nuclear Disaster. AB - OBJECTIVE: This study investigated post-traumatic stress symptoms in relation to the population affected by the Fukushima Nuclear Disaster, one year after the disaster. Additionally, we investigated social factors, such as forced displacement, which we hypothesize contributed to the high prevalence of post traumatic stress. Finally, we report of written narratives that were collected from the impacted population. DESIGN AND SETTINGS: Using the Impact of Event Scale-Revised (IES-R), questionnaires were sent to 2,011 households of those displaced from Fukushima prefecture living temporarily in Saitama prefecture. Of the 490 replies; 350 met the criteria for inclusion in the study. Multiple logistic regression analysis was performed to examine several characteristics and variables of social factors as predictors of probable post-traumatic stress disorder, PTSD. RESULTS: The mean score of IES-R was 36.15+/-21.55, with 59.4% having scores of 30 or higher, thus indicating a probable PTSD. No significant differences in percentages of high-risk subjects were found among sex, age, evacuation area, housing damages, tsunami affected, family split-up, and acquaintance support. By the result of multiple logistic regression analysis, the significant predictors of probable PTSD were chronic physical diseases (OR = 1.97), chronic mental diseases (OR = 6.25), worries about livelihood (OR = 2.27), lost jobs (OR = 1.71), lost social ties (OR = 2.27), and concerns about compensation (OR = 3.74). CONCLUSION: Although there are limitations in assuming a diagnosis of PTSD based on self-report IES-R, our findings indicate that there was a high-risk of PTSD strongly related to the nuclear disaster and its consequent evacuation and displacement. Therefore, recovery efforts must focus not only on medical and psychological treatment alone, but also on social and economic issues related to the displacement, as well. PMID- 27002325 TI - A phase II prospective study of the trastuzumab combined with 5-weekly S-1 and CDDP therapy for HER2-positive advanced gastric cancer. AB - BACKGROUND: We evaluated the efficacy and safety of 5-weekly S-1 and cisplatin combined with trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2 (HER2) for HER2-positive advanced gastric cancer (AGC). METHODS: This phase II study treatment consisted of S-1 (80-120 mg per day) orally on day 1-21, cisplatin (60 mg/m(2)) intravenously on day 8, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival, progression-free survival (PFS), response rate (RR), and safety. RESULTS: A total 22 patients from seven centers were enrolled. In the 20 patients evaluable for analysis, the 1-year survival rate was 70 % (95 % confidence interval (CI) 49.9-90.1 %), and median survival time, PFS, and RR were 15.3, 7.5 months and 41.2 %, respectively. Major grade 3/4 adverse events were neutropenia (30 %), anorexia (30 %), leukopenia (25 %), fatigue (20 %), and anemia (15 %). CONCLUSIONS: Five-weekly S-1 and cisplatin combined with trastuzumab showed effective with favorable safety profile in patients with HER2-positive AGC. PMID- 27002326 TI - (1)H, (15)N and (13)C backbone and side chain resonance assignments of the RRM domain from human RBM24. AB - Tissue development requires the expression of a regulated subset of genes, and it is becoming clear that the process of alternative splicing also plays an important role in the production of necessary tissue-specific isoforms. However, only a few of these tissue-specific splicing factors in mammals have so far been discovered. One of these factors is the RNA-binding protein RBM24 which has been recently identified as a major regulator of alternative splicing in cardiac and skeletal muscle development. The RBM24 protein contains an RNA recognition motif (RRM) domain that presumably mediates the binding to target pre-mRNA required for regulation of the splicing patterns. Here we report (1)H, (15)N and (13)C chemical shift assignments of the backbone and sidechain atoms for the RRM domain from human RBM24. Secondary chemical shift analysis and relaxation measurement confirm the canonical architecture of the RRM domain. The data will allow for atomic level studies aimed at understanding splicing regulation of target genes in heart and muscle development and investigation into a separate role of RBM24 in modulating mRNA stability of genes involved in the p53 tumor suppressor pathway. PMID- 27002327 TI - Psychopathological Symptoms Assessed by a System-Specific Approach Are Related to Global Functioning in Schizophrenic Disorders. AB - BACKGROUND: By mostly using a positive-negative approach, several studies have identified factors that influence day-to-day functioning. We applied a different, system-specific approach to expand the knowledge of this issue. SAMPLING AND METHODS: We recruited a sample of 100 inpatients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Psychopathological characteristics were assessed with the Bern Psychopathology Scale (BPS) and functional characteristics with the Global Assessment of Functioning (GAF) scale. Linear regression analyses were performed with the GAF score as the dependent variable and the global values of the BPS subscores as independent variables. The model was controlled for confounding variables. Spearman rank correlation analyses were used to identify associations between the relevant BPS subdomains and global functioning. RESULTS: Higher absolute global values of the BPS domains language (px2009; = x2009;0.038) and motor behavior (px2009; = x2009;0.049) were significantly associated with lower GAF scores. These findings remained stable after adjusting for potential confounding variables. A statistically significant negative correlation was found between both qualitative symptoms (rx2009; = x2009;-0.273, px2009; = x2009;0.006) and indirect signs (rx2009; = x2009;-0.269, px2009; = x2009;0.007) of the language domain and GAF scores. Also, quantitative (rx2009; = x2009;-0.211, px2009; = x2009;0.035) and qualitative symptoms (rx2009; = x2009;-0.214, px2009; = x2009;0.033) in the motor behavior domain were associated with poorer functioning. CONCLUSIONS: A system-specific approach can describe subgroups of patients with poor functioning. Identifying such subgroups could help to utilize targeted treatment opinions in a timely manner. Another goal of future research is to clarify the underlying neurobiological deficits. PMID- 27002328 TI - Stress fractures: pathophysiology, clinical presentation, imaging features, and treatment options. AB - Stress fracture, in its most inclusive description, includes both fatigue and insufficiency fracture. Fatigue fractures, sometimes equated with the term "stress fractures," are most common in runners and other athletes and typically occur in the lower extremities. These fractures are the result of abnormal, cyclical loading on normal bone leading to local cortical resorption and fracture. Insufficiency fractures are common in elderly populations, secondary to osteoporosis, and are typically located in and around the pelvis. They are a result of normal or traumatic loading on abnormal bone. Subchondral insufficiency fractures of the hip or knee may cause acute pain that may present in the emergency setting. Medial tibial stress syndrome is a type of stress injury of the tibia related to activity and is a clinical syndrome encompassing a range of injuries from stress edema to frank-displaced fracture. Atypical subtrochanteric femoral fracture associated with long-term bisphosphonate therapy is also a recently discovered entity that needs early recognition to prevent progression to a complete fracture. Imaging recommendations for evaluation of stress fractures include initial plain radiographs followed, if necessary, by magnetic resonance imaging (MRI), which is preferred over computed tomography (CT) and bone scintigraphy. Radiographs are the first-line modality and may reveal linear sclerosis and periosteal reaction prior to the development of a frank fracture. MRI is highly sensitive with findings ranging from periosteal edema to bone marrow and intracortical signal abnormality. Additionally, a brief description of relevant clinical management of stress fractures is included. PMID- 27002329 TI - Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation. AB - The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5 MTP) as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs) prevented endothelial hyperpermeability and VE cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK. PMID- 27002330 TI - Modulation of photosynthetic activity and photoprotection in Haematococcus pluvialis cells during their conversion into haematocysts and back. AB - The engagement of different photoprotective mechanisms in the cells of the carotenogenic astaxanthin-accumulating chlorophyte Haematococcus pluvialis (i) under favorable conditions, (ii) in the course of stress-induced haematocyst formation and (iii) during recovery from the stress was studied. To this end, we followed the changes in primary photochemistry, electron flow at the acceptor side of photosystem II, and non-photochemical quenching (NPQ) using PAM chlorophyll fluorimetry. A general trend recorded in the stressed cells undergoing transition to haematocysts (and reversed during recovery from the stress) was a gradual reduction of the photosynthetic apparatus accompanied by down-regulation of energy-dependent photoprotective mechanisms such as NPQ, along with the accumulation of astaxanthin. On this background, a transient up regulation of the photosynthetic activity was detected at the intermediated stages (20-50 h of the stress exposure) of haematocyst formation. This phenomenon was tentatively related with the peak of metabolic activity found earlier in the forming haematocysts. The role of secondary carotenogenesis coupled with a reversible transition from 'active' (energy-dependent) to 'passive' photoprotective mechanisms in the extremely high stress tolerance of carotenogenic phototrophs is discussed. PMID- 27002331 TI - Effect of Octreotide on Hepatic Steatosis in Diet-Induced Obesity in Rats. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) caused by liver lipid dysregulation is linked to obesity. Somatostatin (SST) and its analogs have been used to treat pediatric hypothalamic obesity. However, the application of such drugs for the treatment of NAFLD has not been evaluated. OBJECTIVE: This study aimed to investigate the expression levels of important regulators of hepatic lipid metabolism and the possible effect of the SST analog octreotide on these regulators. METHODS: SD rats were assigned to a control group and a high-fat diet group. Obese rats from the high-fat diet group were further divided into the obese and octreotide-treated groups. The body weight, plasma SST, fasting plasma glucose (FPG), insulin, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acid (FFA) levels were measured. Hepatic steatosis was evaluated based on the liver TG content, HE staining and oil red O staining. The SREBP-1c, ACC1, FAS, MTP, apoB and ADRP expression levels in the liver were also determined by RT PCR, qRT-PCR, western blot or ELISA. RESULTS: The obese rats induced by high-fat diet expressed more SREBP-1c, FAS and ADRP but less MTP protein in the liver than those of control rats, whereas octreotide intervention reversed these changes and increased the level of apoB protein. Compared to the control group, obese rats showed increased liver ACC1, SREBP-1c and apoB mRNA levels, whereas octreotide treated rats showed decreased mRNA levels of apoB and SREBP-1c. This was accompanied by increased body weight, liver TG contents, FPG, TG, TC, LDL-C, FFA, insulin and derived homeostatic model assessment (HOMA) values. Octreotide intervention significantly decreased these parameters. Compared to the control group, the obese group showed a decreasing trend on plasma SST levels, which were significantly increased by the octreotide intervention. CONCLUSION: Octreotide can ameliorate hepatic steatosis in obese rats, possibly by decreasing hepatic lipogenesis and increasing TG export from hepatocytes. PMID- 27002332 TI - Antagonistic potential of Pseudomonas graminis 49M against Erwinia amylovora, the causal agent of fire blight. AB - In a previous study (Mikicinski et al. in Eur J Plant Pathol, doi: 10.1007/s10658 015-0837-y , 2015), we described the characterization of novel strain 49M of Pseudomonas graminis, isolated from the phyllosphere of apple trees in Poland showing a good protective activity against fire blight on different organs of host plants. We now report investigations to clarify the basis for this activity. Strain 49M was found to produce siderophores on a medium containing complex CAS Fe(3+) and HDTMA, but was not able to produce N-acyl homoserine lactones (AHLs). Moreover, it formed a biofilm on polystyrene and polyvinyl chloride (PVC) surfaces. Strain 49M gave a positive reaction in PCR with primers complementary to gacA, the regulatory gene influencing the production of several secondary metabolites including antibiotics. The genes prnD (encoding pyrrolnitrin), pltC, pltB (pyoluteorin), phlD (2,4-diacetyl-phloroglucinol) and phzC as well as phzD (and their homologs phzF and phzA encoding phenazine), described for antagonistic fluorescent pseudomonads, however, were not detected. Research into the biotic relationship between strain 49M and Erwinia amylovora strain Ea659 on five microbiological media showed that this strain clearly inhibited the growth of the pathogen on King's B and nutrient agar with glycerol media, to a very small extent on nutrient agar with sucrose, and not at all on Luria-Bertani agar. On medium 925, strain 49M even stimulated E. amylovora growth. The addition of ferric chloride to King's B resulted in the loss of its inhibitory ability. Testing the survival of 49M in vitro showed its resistance to drought, greater than that of E. amylovora. PMID- 27002333 TI - Photometric Compliance of Tablet Screens and Retro-Illuminated Acuity Charts As Visual Acuity Measurement Devices. AB - Mobile technology is increasingly used to measure visual acuity. Standards for chart-based acuity tests specify photometric requirements for luminance, optotype contrast and luminance uniformity. Manufacturers provide some photometric data but little is known about tablet performance for visual acuity testing. This study photometrically characterised seven tablet computers (iPad, Apple inc.) and three ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity charts with room lights on and off, and compared findings with visual acuity measurement standards. Tablet screen luminance and contrast were measured using nine points across a black and white checkerboard test screen at five arbitrary brightness levels. ETDRS optotypes and adjacent white background luminance and contrast were measured. All seven tablets (room lights off) exceeded the most stringent requirement for mean luminance (>= 120 cd/m2) providing the nominal brightness setting was above 50%. All exceeded contrast requirement (Weber >= 90%) regardless of brightness setting, and five were marginally below the required luminance uniformity threshold (Lmin/Lmax >= 80%). Re-assessing three tablets with room lights on made little difference to mean luminance or contrast, and improved luminance uniformity to exceed the threshold. The three EDTRS charts (room lights off) had adequate mean luminance (>= 120 cd/m2) and Weber contrast (>= 90%), but all three charts failed to meet the luminance uniformity standard (Lmin/Lmax >= 80%). Two charts were operating beyond manufacturer's recommended lamp replacement schedule. With room lights on, chart mean luminance and Weber contrast increased, but two charts still had inadequate luminance uniformity. Tablet computers showed less inter-device variability, higher contrast, and better luminance uniformity than charts in both lights-on and lights-off environments, providing brightness setting was >50%. Overall, iPad tablets matched or marginally out-performed ETDRS charts in terms of photometric compliance with high contrast acuity standards. PMID- 27002334 TI - Filling in the Gap of Human Chromosome 4: Single Molecule Real Time Sequencing of Macrosatellite Repeats in the Facioscapulohumeral Muscular Dystrophy Locus. AB - A majority of facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of macrosatellite repeats called D4Z4 that are located in the subtelomeric region of human chromosome 4q35. Sequencing the FSHD locus has been technically challenging due to its long size and nearly identical nature of repeat elements. Here we report sequencing and partial assembly of a BAC clone carrying an entire FSHD locus by a single molecule real time (SMRT) sequencing technology which could produce long reads up to about 18 kb containing D4Z4 repeats. De novo assembly by Hierarchical Genome Assembly Process 1 (HGAP.1) yielded a contig of 41 kb containing all but a part of the most distal D4Z4 element. The validity of the sequence model was confirmed by an independent approach employing anchored multiple sequence alignment by Kalign using reads containing unique flanking sequences. Our data will provide a basis for further optimization of sequencing and assembly conditions of D4Z4. PMID- 27002335 TI - Molecular Imaging of Pituitary Pathology. AB - The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas. PMID- 27002336 TI - Biomass-Derived Thermally Annealed Interconnected Sulfur-Doped Graphene as a Shield against Electromagnetic Interference. AB - Electrically conductive thin carbon materials have attracted remarkable interest as a shielding material to mitigate the electromagnetic interference (EMI) produced by many telecommunication devices. Herein, we developed a sulfur-doped reduced graphene oxide (SrGO) with high electrical conductivity through using a novel biomass, mushroom-based sulfur compound (lenthionine) via a two-step thermal treatment. The resultant SrGO product exhibited excellent electrical conductivity of 311 S cm(-1), which is 52% larger than 205 S cm(-1) for undoped rGO. SrGO also exhibited an excellent EMI shielding effectiveness of 38.6 dB, which is 61% larger than 24.4 dB measured for undoped rGO. Analytical examinations indicate that a sulfur content of 1.95 atom % acts as n-type dopant, increasing electrical conductivity and, therefore, EMI shielding of doped graphene. PMID- 27002337 TI - Development and Evaluation of a Parallel Reaction Monitoring Strategy for Large Scale Targeted Metabolomics Quantification. AB - Recent advances in mass spectrometers which have yielded higher resolution and faster scanning speeds have expanded their application in metabolomics of diverse diseases. Using a quadrupole-Orbitrap LC-MS system, we developed an efficient large-scale quantitative method targeting 237 metabolites involved in various metabolic pathways using scheduled, parallel reaction monitoring (PRM). We assessed the dynamic range, linearity, reproducibility, and system suitability of the PRM assay by measuring concentration curves, biological samples, and clinical serum samples. The quantification performances of PRM and MS1-based assays in Q Exactive were compared, and the MRM assay in QTRAP 6500 was also compared. The PRM assay monitoring 237 polar metabolites showed greater reproducibility and quantitative accuracy than MS1-based quantification and also showed greater flexibility in postacquisition assay refinement than the MRM assay in QTRAP 6500. We present a workflow for convenient PRM data processing using Skyline software which is free of charge. In this study we have established a reliable PRM methodology on a quadrupole-Orbitrap platform for evaluation of large-scale targeted metabolomics, which provides a new choice for basic and clinical metabolomics study. PMID- 27002338 TI - Optimized Basis Sets for the Environment in the Domain-Specific Basis Set Approach of the Incremental Scheme. AB - Minimal basis sets, denoted DSBSenv, based on the segmented basis sets of Ahlrichs and co-workers have been developed for use as environmental basis sets for the domain-specific basis set (DSBS) incremental scheme with the aim of decreasing the CPU requirements of the incremental scheme. The use of these minimal basis sets within explicitly correlated (F12) methods has been enabled by the optimization of matching auxiliary basis sets for use in density fitting of two-electron integrals and resolution of the identity. The accuracy of these auxiliary sets has been validated by calculations on a test set containing small- to medium-sized molecules. The errors due to density fitting are about 2-4 orders of magnitude smaller than the basis set incompleteness error of the DSBSenv orbital basis sets. Additional reductions in computational cost have been tested with the reduced DSBSenv basis sets, in which the highest angular momentum functions of the DSBSenv auxiliary basis sets have been removed. The optimized and reduced basis sets are used in the framework of the domain-specific basis set of the incremental scheme to decrease the computation time without significant loss of accuracy. The computation times and accuracy of the previously used environmental basis and that optimized in this work have been validated with a test set of medium- to large-sized systems. The optimized and reduced DSBSenv basis sets decrease the CPU time by about 15.4% and 19.4% compared with the old environmental basis and retain the accuracy in the absolute energy with standard deviations of 0.99 and 1.06 kJ/mol, respectively. PMID- 27002339 TI - Au Nanoparticles Decorated TiO2 Nanotube Arrays as a Recyclable Sensor for Photoenhanced Electrochemical Detection of Bisphenol A. AB - A photorefreshable and photoenhanced electrochemical sensing platform for bisphenol A (BPA) detection based on Au nanoparticles (NPs) decorated carbon doped TiO2 nanotube arrays (TiO2/Au NTAs) is described. The TiO2/Au NTAs were prepared by quick annealing of anodized nanotubes in argon, followed by controllable electrodeposition of Au NPs. The decoration of Au NPs not only improved photoelectrochemical behavior but also enhanced electrocatalytic activities of the resulted hybrid NTAs. Meanwhile, the high photocatalytic activity of the NTAs allowed the electrode to be readily renewed without damaging the microstructures and surface states after a short UV treatment. The electrochemical detection of BPA on TiO2/Au NTAs electrode was significantly improved under UV irradiation as the electrode could provide fresh reaction surface continuously and the further increased photocurrent resulting from the improved separation efficiency of the photogenerated electron-hole pairs derived from the consumption of holes by BPA. The results showed that the refreshable TiO2/Au NTAs electrode is a promising sensor for long-term BPA monitoring with the detection limit (S/N = 3) of 6.2 nM and the sensitivity of 2.8 MUA.MUM( 1).cm(-2). PMID- 27002340 TI - Pelianthinarubins A and B, Red Pyrroloquinoline Alkaloids from the Fruiting Bodies of the Mushroom Mycena pelianthina. AB - Pelianthinarubin A (1) and pelianthinarubin B (2), two previously unknown pyrroloquinoline alkaloids, have been isolated from fruiting bodies of Mycena pelianthina. The structures of these alkaloids have been deduced from their HR (+)-ESIMS and 2D NMR data. The absolute configurations of the pelianthinarubins A (1) and B (2) were assigned by analysis of the NOE correlations and coupling constants and by comparison of the CD spectra of 1 and 2 and of hercynine obtained by degradation of 1 with suitable compounds of known absolute configuration. The pelianthinarubins A (1) and B (2), which contain an S hercynine moiety, differ considerably from the known pyrroloquinoline alkaloids from marine organisms and other Mycena species, such as the mycenarubins, the haematopodins, and the sanguinones. PMID- 27002342 TI - Role of myokines in the maintenance of whole-body metabolic homeostasis. AB - Obesity is reaching epidemic proportions in developed countries and is on the rise in developing countries. Obesity-related changes in lipid and glucose metabolism predispose to the development of metabolic syndrome and type 2 diabetes. Skeletal muscle constitutes about 40 percent of total body weight and is unique compared to other muscle types since it is one of the most important organs for insulin-dependent glucose metabolism in humans. Abnormalities in skeletal muscle lipid and glucose metabolism as well as abnormal accumulation of intramyocellular lipids could predispose for the development of type 2 diabetes. Skeletal muscle synthesizes and secretes factors with autocrine/paracrine/endocrine functions that can regulate skeletal muscle metabolism as well as affect other organs. These factors secreted by skeletal muscle are called myokines. Secretion and action of myokines is regulated by physiological conditions. Some myokines have positive effect on metabolism, improving functions of multiple organs. Yet, other myokines are released under pathological conditions and might exacerbate abnormal metabolic functions. Expression and/or secretion of a number of myokines are regulated by exercise and therefore might mediate positive effects of physical activity on whole-body metabolism. In the current review we summarized current knowledge on some of the myokines with important physiological functions in lipid and glucose metabolism. A better understanding of the effects of myokines on whole-body metabolism can aid in development of the future pharmacologic therapies for counteracting the current worldwide obesity epidemic and obesity-mediated abnormalities. PMID- 27002341 TI - Fast Magnetic Domain-Wall Motion in a Ring-Shaped Nanowire Driven by a Voltage. AB - Magnetic domain-wall motion driven by a voltage dissipates much less heat than by a current, but none of the existing reports have achieved speeds exceeding 100 m/s. Here phase-field and finite-element simulations were combined to study the dynamics of strain-mediated voltage-driven magnetic domain-wall motion in curved nanowires. Using a ring-shaped, rough-edged magnetic nanowire on top of a piezoelectric disk, we demonstrate a fast voltage-driven magnetic domain-wall motion with average velocity up to 550 m/s, which is comparable to current-driven wall velocity. An analytical theory is derived to describe the strain dependence of average magnetic domain-wall velocity. Moreover, one 180 degrees domain-wall cycle around the ring dissipates an ultrasmall amount of heat, as small as 0.2 fJ, approximately 3 orders of magnitude smaller than those in current-driven cases. These findings suggest a new route toward developing high-speed, low-power dissipation domain-wall spintronics. PMID- 27002343 TI - Dependence of the Nature of the Pedaling Activity on Maximal Aerobic Power in Cycling. AB - PURPOSE: To analyze the effect of the pedaling activity in different 4-min time trials (TT4s) (laboratory and field conditions) and compare TT4 and maximal aerobic power (MAP) determined from the classical incremental exercise test in laboratory. It was hypothesized that the exercises performed on the field would determine higher physical (power output [PO]) and mental involvements due to different environmental conditions. METHODS: Sixteen male cyclists underwent an incremental test to exhaustion and 3 TT4s under different conditions: cycle ergometer (CE), level ground (LG), and uphill (UP). RESULTS: Correlation was observed for PO with a trivial effect size and narrow limits of agreement between MAP and CE TT4 (r = .96, P < .001). The comparison between the CE, LG, and UP tests indicates that PO was significantly higher in UP than in CE (+8.0%, P < .001) and LG (+11.0%, P < .001). CONCLUSIONS: The results suggest that PO depends on the nature of the pedaling activity. Moreover, PO under CE TT4 is a relevant predictor of MAP. It seems important to measure MAP by taking into account the cycling conditions, considering that coaches and scientists use this parameter to assess the aerobic potential of athletes and determine the exercise intensities useful for monitoring adaptation to training. PMID- 27002344 TI - Gestational weight gain and its related social and demographic factors in health care settings of rural and urban areas in northwest Iran. AB - The current study was aimed to evaluate gestational weight gain and its socio demographic determinants among pregnant women in north-west of Iran. In the current cross-sectional study, four hundred eighty one pregnant women aged 26.12 +/- 7.45 years were enrolled. Data on pre-pregnancy weight, height, age, educational attainment, parity, household size, hemoglobin status and total pregnancy weight gain were extracted from routine health center records. The pregnant women were categorized based on their pre-pregnancy body mass index (BMI) as underweight, normal weight and overweight or obese according to the 2009 Institute of Medicine (IOM) recommendations. Participants were also classified according to their educational level into three 'some school', 'high school' and 'college' groups. Gestational weight gain in 27.6% of pregnant women was in normal IOM recommended range; while, weight gain in 49% and 23.2% of pregnant women was below and above recommended range respectively. Women with high educational attainment (>=12 years) have significantly higher weight gain compared with low-educated women (<12 years) (P < 0.001). Age was in negative relationship with gestational weigh gain even after adjusting for confounder effects of residency, educational attainment and household size (r = 0.2, P < 0.001). Our data showed a high prevalence of abnormal gestational weight gain in pregnant women attending to public health centers in northwest of Iran. Moreover educational level, parity and age were significant determinants of gestational weight gain in pregnancy. Special attention should be focused on prenatal nutritional status and health care programs in current health care services in Iran. PMID- 27002345 TI - Reason of Choroidal Thickening in Rheumatoid Arthritis May be Temperature Rise of the Body. PMID- 27002346 TI - Acute Corneal Toxicity of Combined Antiglaucoma Topical Eyedrops. AB - PURPOSE: To investigate the corneal toxicity of three combined antiglaucoma topical eyedrops using transepithelial electrical resistance (TER) and scanning electron microscopy (SEM). METHODS: Corneal TER changes after a 60-s exposure to latanoprost/timolol with 0.02% benzalkonium chloride (BAC), travoprost/timolol with polyquaternium-1, and dorzolamide/timolol with 0.005% BAC were measured in living rabbits. Corneal damage was also examined by SEM. Hank's balanced salt solution (HBSS) was used as a control. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to latanoprost/timolol with 0.02% BAC. Travoprost/timolol with polyquaternium-1 and dorzolamide/timolol with 0.005% BAC did not produce any significant decrease in the corneal TER as compared to HBSS control eyes. SEM revealed that superficial cells of corneas treated with latanoprost/timolol with 0.02% BAC were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to travoprost/timolol with polyquaternium-1 or dorzolamide/timolol with 0.005% BAC appeared normal and had normal microvilli under SEM examinations. CONCLUSION: The corneal toxicity of latanoprost/timolol with 0.02% BAC is greater than that of travoprost/timolol with polyquaternium-1 and dorzolamide/timolol with 0.005% BAC. Latanoprost/timolol contains 0.02% BAC, which may be responsible for the corneal toxicity. PMID- 27002348 TI - Acute Alcohol Use and Injury Patterns in Young Adult Prehospital Patients. AB - The objective was to determine if acute alcohol consumption is associated with differences in injury pattern among young adult patients with traumatic injuries presenting to emergency medical services (EMS). A cross-sectional, retrospective review of prehospital patient care reports (PCRs) was conducted evaluating injured patients who presented to a collegiate EMS agency from January 1, 2011 to December 31, 2012. Included patients were age 18-24 y and sustained an injury within the previous 24 h. PCRs were reviewed independently by two abstractors to determine if the patient was documented to have acutely consumed alcohol proximate to his/her injury. Primary and secondary sites of regional body injury were recorded. Injury severity was recorded using the Revised Trauma Score (RTS). The association between primary injury site and acute alcohol use was assessed using a chi-square test. Multiple logistic regression was used to control for sex in predicting injury type. Of 440 injured patients, 135 (30.6%) had documented alcohol use prior to injury. Acute alcohol consumption altered the overall pattern of regional injury (p < 0.001). Alcohol users were more likely to present with injury secondary to assault, fall/trip, and unknown mechanism of injury (p < 0.001, all comparisons). RTS scores were statistically lower in the alcohol group (p < 0.001), although the clinical significance of this is unclear. Controlling for sex, acute alcohol consumption predicted increased risk of head/neck injury 5.59-fold (p < 0.001). Acute alcohol use in collegiate EMS patients appears to alter injury patterns in young adults and increases risk of head/neck injury. EMS providers in similar agencies should consider these trends when assessing and treating injured college-aged patients. PMID- 27002349 TI - Effective Use of Naloxone by Law Enforcement in Response to Multiple Opioid Overdoses. AB - OBJECTIVE: Growing rates of opioid abuse and overdose throughout the nation have lead some community organizations to develop naloxone administration programs. METHODS: In Pitt County North Carolina, two of our law enforcement agencies were trained in the identification of opioid overdose and use of naloxone therapy. RESULTS: Attributed partially to introduction of fentanyl into the illicit drug market, our community experienced a 48-hour period in which officers successfully deployed five doses of antagonist medication to four individuals. CONCLUSION: This article presents case descriptions demonstrating the feasibility and safety of law enforcement naloxone programs. PMID- 27002347 TI - MicroRNA-26a/b and their host genes synergistically regulate triacylglycerol synthesis by targeting the INSIG1 gene. AB - The microRNA-26 (miR-26) family is known to control adipogenesis in non ruminants. The genomic loci of miR-26a and miR-26b have been localized in the introns of genes encoding for the proteins of the C-terminal domain RNA polymerase II polypeptide A small phosphatase (CTDSP) family. Insulin-induced gene 1 (INSIG1) encodes a protein with a key role in the regulation of lipogenesis in rodent liver. In the present study, we investigated the synergistic function of the miR-26 family and their host genes in goat mammary epithelial cells (GMEC). Downregulation of miR-26a/b and their host genes in GMEC decreased the expression of genes relate to fatty acid synthesis (PPARG, LXRA, SREBF1, FASN, ACACA, GPAM, LPIN1, DGAT1 and SCD1), triacylglycerol accumulation and unsaturated fatty acid synthesis. Luciferase reporter assays confirmed INSIG1 as a direct target of miR-26a/b. Furthermore, inhibition of the CTDSP family also downregulated the expression of INSIG1. Taken together, our findings highlight a functional association of miR-26a/b, their host genes and INSIG1, and provide new insights into the regulatory network controlling milk fat synthesis in GMEC. The data indicate that targeting this network via nutrition might be important for regulating milk fat synthesis in ruminants. PMID- 27002350 TI - Patients Immobilized with a Long Spine Board Rarely Have Unstable Thoracolumbar Injuries. AB - Most Emergency Medical Services (EMS) protocols require spine immobilization with both a cervical collar and long spine board for patients with suspected spine injuries. The goal of this research was to determine the prevalence of unstable thoracolumbar spine injuries among patients receiving prehospital spine immobilization: a 4-year retrospective review of adult subjects who received prehospital spine immobilization and were transported to a trauma center. Prehospital and hospital records were linked. Data was reviewed to determine if spine imaging was ordered, whether acute thoracolumbar fractures, dislocations, or subluxations were present. Thoracolumbar injuries were classified as unstable if operative repair was performed. Prehospital spine immobilization was documented on 5,593 unique adult subjects transported to the study hospital. A total of 5,423 (97.0%) prehospital records were successfully linked to hospital records. The subjects were 60.2% male, with a mean age of 40.6 (SD = 17.5) years old. An total of 5,286 (97.4%) subjects had sustained blunt trauma. Hospital providers ordered imaging to rule out spine injury in 2,782 (51.3%) cases. An acute thoracolumbar fracture, dislocation, or subluxation was present in 233 (4.3%) cases. An unstable injury was present in 29 (0.5%) cases. No unstable injuries were found among the 951 subjects who were immobilized following ground level falls. Hospital providers ordered at least one spine x-ray or CT in most patients, and a thoracolumbar imaging in half of all patients immobilized. Only 0.5% of patients who received prehospital spine immobilization had an unstable thoracolumbar spine injury. PMID- 27002352 TI - [Formula: see text]Parental ratings of daily behavior and child cognitive test performance after pediatric mild traumatic brain injury. AB - This study aimed to evaluate the degree to which the Behavior Rating Inventory of Executive Function (BRIEF) and Child Behavior Checklist (CBCL) measure overlapping vs. distinct constructs in pediatric patients with mild traumatic brain injury (TBI), and to examine the demographic and injury correlates of such constructs as well as those of cognitive test performance. A total of 100 parents completed the BRIEF and the CBCL within 1 to 12 months after the injury of their child. Groups were contrasted based on the presence vs. absence of impairment on, respectively, the BRIEF and the CBCL. Exploratory maximum likelihood factor analysis was used to evaluate latent constructs. Correlates of the various factor scores were evaluated through regression analysis and contrasted with those of a test of verbal learning and memory.The results revealed that the BRIEF and the CBCL disagree about the presence vs. absence of impairment in about one quarter of cases. A prior history of attention deficit/hyperactivity disorder (ADHD) was associated with an increased likelihood of impairment on both the BRIEF and the CBCL, whereas prior outpatient psychiatric treatment was associated with the increased likelihood of selective impairment on the CBCL. Latent constructs manifested themselves along cognitive regulation, emotional adjustment and behavioral regulation factors. Whereas premorbid characteristics were the exclusive correlates of these factors, performance on a test of verbal learning and memory was negatively affected by intracranial lesions on neuroimaging.It is concluded that the BRIEF and the CBCL offer complementary and non-redundant information about daily functioning after pediatric mild TBI. The correlates of cognitive test performance and parental behavior ratings after such injuries are different and reflect a divergence between premorbid and injury-related influences. PMID- 27002351 TI - Relationships of Feeding and Mother's Own Milk with Fecal Calprotectin Levels in Preterm Infants. AB - OBJECTIVE: To describe longitudinal effects of feeding volume and type of milk on fecal calprotectin (f-CP) in very low-birth weight (VLBW) infants. STUDY DESIGN: Prospective data were collected across Neonatal Intensive Care Unit (NICU) admission for 6 weeks or until discharge in 75 VLBW neonates. The mean gestational age on entry into the study was 29 weeks. RESULTS: Seventy-four (99%) mothers provided expressed milk in varying amounts. Twenty-three mothers (31%) provided exclusive mother's own milk (MOM) throughout. Preterm infant formula (PIF) and pasteurized donor milk were added to feedings of remaining infants. Pooled MOM was analyzed weekly for levels of a panel of cytokines, chemokines, and growth factors, and secretory Immunoglobulin A (sIgA) so that the exact amount of exposure to the gut of these milk bioactives could be estimated. f-CP levels ranged from 160 to 350 MUg/g stool. Total feeding volume was positively associated with f-CP, controlling for infant weight, and f-CP levels rose across time. Exclusive MOM feedings for the entire measurement period were associated with rising levels of f-CP, but mixed feedings (MOM with added PIF or pasteurized donor milk (PDM) did not show this increase over time. CONCLUSION: The presence of f-CP may represent a response to milk volumes and MOM, which represents normal development rather than always implicating pathological inflammation in the VLBW infant. PMID- 27002353 TI - Parental mediation of adolescent media use and demographic factors as predictors of Kenyan high school students' exposure to sexual content in television. AB - Research in Western nations suggests that parents' involvement in their children's media use can make a difference in how adolescents select, process and respond to sexual television messages. Little or no published research has investigated this issue in sub-Saharan Africa, even though adolescents and young adults remain among the groups at highest risk for HIV transmission. This study investigated the relationship between Kenyan adolescents' level of exposure to sexual television content and their parents' mediation of their television use. A cluster sample of 427 Nairobi public high school students was surveyed regarding parental mediation of their media use and their intake of sexual television content. Co-viewing with opposite sex friends was associated with higher intake of sexual TV content. This relationship was stronger among boarding school students than among day school students. Parental mediation and co-viewing variables predicted three times as much variance among boarding than among day school students. PMID- 27002354 TI - Involving parents from the start: formative evaluation for a large randomised controlled trial with Botswana Junior Secondary School students. AB - While HIV prevention research conducted among adolescent populations may encounter parental resistance, the active engagement of parents from inception to trial completion may alleviate opposition. In preparation for implementing a large randomised controlled trial (RCT) examining the efficacy of a behavioural intervention targeting adolescent sexual risk behaviours, a formative evaluation was undertaken to assess parental reactions to the proposed trial. Six focus groups were conducted with parents of adolescents (aged 13-17) from rural, peri urban and urban junior secondary schools in Botswana. Focus groups explored comprehension and acceptability among parents of the forthcoming trial including HSV-2 testing, the return of results to the adolescent (not the parent), trial information materials and the parental consent process. Parents welcomed the study and understood and accepted its moral and ethical considerations. Their reactions regarding return of HSV-2 results only to adolescents (not the parent) were mixed. Parents understood the consent process and most agreed to consent, while indicating their desire to remain informed and involved throughout the RCT. The focus group discussions (FGDs) provided valuable information and insights that helped strengthen the study. As a result of parents' feedback, counselling procedures were strengthened and direct linkages to local services and care were made. Informational materials were revised to increase clarity, and materials and procedures were developed to encourage and support parental involvement and parent-child dialogue. Ultimately, parental feedback led to a decision by the Government of Botswana to allow parents to access their child's HSV-2 test results. PMID- 27002355 TI - The use of cash transfers for HIV prevention--are we there yet? AB - Poverty and social inequality are significant drivers of the HIV epidemic and are risk factors for acquiring HIV. As such, many individuals worldwide are at risk for new HIV infection, especially young women in East and Southern Africa. By addressing these drivers, social protection programmes may mitigate the impact of poverty and social inequality on HIV risk. There is reason to believe that social protection can be used successfully for HIV prevention; social protection programmes, including cash transfers, have led to positive health outcomes and behaviour in other contexts, and they have been used successfully to promote education and increased income and employment opportunities. Furthermore, cash transfers have influenced sexual behaviour of young women and girls, thereby decreasing sexual risk factors for HIV infection. When HIV outcomes have been measured, several randomised controlled trials have shown that indirectly, cash transfers have led to reduced HIV prevalence and incidence. In these studies, school attendance and safer sexual health were directly incentivised through the cash transfer, yet there was a positive effect on HIV outcomes. In this review, we discuss the growth of social protection programmes, their benefits and impact on health, education and economic potential, and how these outcomes may affect HIV risk. We also review the studies that have shown that cash transfers can lead to reduced HIV infection, including study limitations and what questions still remain with regard to using cash transfers for HIV prevention. PMID- 27002356 TI - Oral histories of HIV/AIDS support group members, NGO workers and home-based carers in KwaZulu-Natal. AB - The purpose of this paper is to bring to the attention of the AIDS research community the existence of an oral history project known as the Memories of AIDS Project. The project focused on HIV/AIDS support group members, non-governmental organisation (NGO) workers and home-based carers in the Umgungundlovu (Pietermaritzburg) District Municipality, South Africa. The project was carried out by the Sinomlando Centre for Oral History and Memory Work, a research and community development centre of the University of KwaZulu-Natal, over a period of three years (2011-2013). Sixty-five individual oral history interviews of 1 to 4 hours duration and 11 focus group sessions were recorded, transcribed and translated from isiZulu into English when necessary. The life stories of community workers and support group members documented in the interviews show, on the part of the informants, a remarkable degree of agency and assertiveness in matters of sexuality, gender relations and religious beliefs. They found innovative ways of navigating through the conflicting claims of biomedicine, Christianity and African traditional religion. As much as the epidemic caused grief and suffering, it opened the door to new knowledge and new opportunities. PMID- 27002357 TI - HIV/AIDS among pastoralists and refugees in north-east Africa: a neglected problem. AB - The eight member states (Djibouti, Eritrea, Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) of the Intergovernmental Authority for Development (IGAD) have the largest proportions of cross-border mobile pastoralists and refugees in Africa. Although all IGAD countries have had national HIV/AIDS prevention, care and treatment programmes since the late 1980s, the IGAD Regional HIV & AIDS Partnership Program was (IRAPP) established in 2007 to mitigate the challenges of HIV among neglected pastoral and refugee communities. This article assesses vulnerability of pastoralists and refugee communities to HIV and interventions targeting these groups in the IGAD countries. Outcomes from this study may serve as a baseline for further research and to improve interventions. Published articles were accessed through web searches using PubMed and Google Scholar engines and unpublished documents were collected manually. The search terms were HIV risk behaviour, vulnerability, HIV prevalence and interventions, under the headings pastoralists, refugees, IGAD and north-east Africa for the period 2001-2014. Of the 214 documents reviewed, 78 met the inclusion criteria and were included. Most HIV/AIDS related studies focusing of pastoral communities in IGAD countries were found to be limited in scope and coverage but reveal precarious situations. Sero-prevalence among various pastoral populations ranged from 1% to 21% in Ethiopia, Kenya, Somalia and Uganda and from 1% to 5% among refugees in Sudan, Kenya and Uganda. Socioeconomic, cultural, logistic, infrastructure and programmatic factors were found to contribute to continuing vulnerability to HIV. Interventions need to be further contextualised to the needs of those impoverished populations and integrated into national HIV/AIDS programmes. HIV/AIDS remains a major public health concern among the pastoral and refugee communities of IGAD countries. This calls for IGAD to collaborate with national and international partners in designing and implementing more effective prevention and control programmes. Furthermore, interventions must extend beyond the health sector and improve the livelihood of these populations. PMID- 27002358 TI - Gender inequality dynamics in the prevention of a heterosexual HIV epidemic in sub-Saharan Africa. AB - This paper critiques the approach to the elimination of gender inequality as an HIV prevention strategy in the just ended era of the Millennium Development Goals, with the aim of contributing to the formulation of policy guidelines for sub-Saharan Africa in the Sustainable Development Goals. The aim is to underscore the mutual responsibility of women and men in achieving a sustainable HIV response and ending the epidemic. While taking into account the real vulnerability of women, prevention programmes can reflect gender dynamics more accurately so that attention is given to the role of both sexes in propagating - or stemming - a predominantly heterosexual HIV epidemic. More emphasis could be given to the harm caused to both men and women by certain norms related to masculinity and sexuality, and the subsequent need for combined efforts in reducing intimate partner violence and concurrency. The empowerment and engagement of both women and men as agents of change would need to be dealt with more creatively. PMID- 27002359 TI - New insights into HIV epidemic in South Africa: key findings from the National HIV Prevalence, Incidence and Behaviour Survey, 2012. AB - This article presents key findings from the 2012 HIV prevalence, incidence and behaviour survey conducted in South Africa and explores trends in the HIV epidemic. A representative household based survey collected behavioural and biomedical data among people of all ages. Chi-squared test for association and formal trend tests (2002, 2005, 2008 and 2012) were used to test for associations and trends in the HIV epidemic across the four surveys. In 2012 a total of 38 431 respondents were interviewed from 11 079 households; 28 997 (67.5%) of 42 950 eligible individuals provided blood specimens. HIV prevalence was 12.2% [95% CI: 11.4-13.1] in 2012 with prevalence higher among females 14.4% than males 9.9%. Adults aged 25-49 years were most affected, 25.2% [95% CI: 23.2-27.3]. HIV prevalence increased from 10.6% [95%CI: 9.8-11.6] in 2008 to 12.2% [95% CI: 11.4 13.1] in 2012 (p < 0.001). Antiretroviral treatment (ART) exposure doubled from 16.6% in 2008 to 31.2% in 2012 (p < 0.001). HIV incidence in 2012 among persons 2 years and older was 1.07% [95% CI: 0.87-1.27], with the highest incidence among Black African females aged 20-34 years at 4.5%. Sexual debut before 15 years was reported by 10.7% of respondents aged 15-24 years, and was significantly higher among male youth than female (16.7% vs. 5.0% respectively, p < 0.001). Reporting of multiple sexual partners in the previous 12 months increased from 11.5% in 2002 to 18.3% in 2012 (p < 0.001). Condom use at last sex dropped from 45.1% in 2008 to 36.2% in 2012 (p < 0.001). Levels of accurate HIV knowledge about transmission and prevention were low and had decreased between 2008 and 2012 from 31.5% to 26.8%. South Africa is on the right track with scaling up ART. However, there have been worrying increases in most HIV-related risk behaviours. These findings suggest that there is a need to scale up prevention methods that integrate biomedical, behavioural, social and structural prevention interventions to reverse the tide in the fight against HIV. PMID- 27002360 TI - Home-based rehabilitation interventions for adults living with HIV: a scoping review. AB - Home-based rehabilitation (HBR) has been shown to improve the lives of people living with a wide range of chronic diseases in resource-rich settings. This may also be a particularly effective strategy in resource-poor settings, where access to institution-based rehabilitation is limited. This review aimed to summarise and discuss the evidence related to the effectiveness of home-based rehabilitation (HBR) interventions designed specifically for adults living with HIV. A scoping review methodology was employed, involving systematic search techniques and appraisal of appropriate evidence. English-language journal articles that assessed the quality of life or functional ability outcomes of HBR interventions for adults living with HIV were considered for this review. Out of an initial 1 135 publications retrieved from the search of databases, six articles met this review's inclusion criteria. While this review highlights the scarcity of empirical evidence related to HBR interventions for adults living with HIV, the findings of these six articles are that HBR is a safe management option that may confer a number of physical and psychological benefits for this population. Future research on HBR interventions should include a wider range of assessment measures, including cost-benefit analyses and specific tools designed to assess the functional ability and participation in activities of daily living of participants involved in these programmes. In particular, more research on HBR is required in resource-poor environments, such as sub-Saharan Africa where HIV is endemic, to assess whether this is a feasible strategy that is both effective and practical in the areas that may need it most. PMID- 27002361 TI - A Mother's Story: Fighting Rett Syndrome Head On. PMID- 27002362 TI - Variations of malondialdehyde in pre-eclampsia. AB - Malondialdehyde, as a biomarker of oxidative stress in pre-eclampsia, is discussed in terms of the determination methods, the validity of the obtained data, and variations in different studies, and it is concluded that there is a need for re-validation of the analytical methods and re-evaluation of its role as a biomarker of oxidative stress. PMID- 27002363 TI - Dose-response association between maternal body mass index and small for gestational age: a meta-analysis. AB - OBJECTIVE: This study was performed to determine the dose-response relationships between maternal anthropometric variables and risk of small for gestational age (SGA). METHODS: Linear and nonlinear dose-response meta-analyses were performed to summarize the adjusted relative risks of SGA. Ten databases, including PubMed (MEDLINE), were searched. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: A total of 323 243 subjects were extracted from high-quality studies to evaluate maternal body mass index (BMI) (n = 9). The generalizability of the findings regarding height and weight (n = 3 and 2, respectively) was limited. The non-linear model (p for non-linearity < 0.05) showed a significant and inverse association of maternal BMI with risk of SGA, although only two of nine studies involved obese women (i.e. BMI >= 30 kg/m2). The slope of the dose response curve between maternal BMI and SGA (i.e. the amount of reduction in SGA risk) decreased gradually. CONCLUSIONS: SGA risk may be reduced by increasing BMI of normal (i.e. 18.5 kg/m2 <= BMI < 25 kg/m2) and overweight women (i.e. 25 kg/m2 <= BMI < 30 kg/m2), but the most marked reduction is achieved by increasing BMI of underweight women (i.e. BMI < 18.5 kg/m2). PMID- 27002368 TI - Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa. AB - As more human immunodeficiency virus (HIV)-infected patients access combination antiretroviral therapy (cART), higher proportions of newly infected patients may be infected with drug-resistant viruses. Regular surveillance of transmitted drug resistance (TDR) is required in southern Africa where high rates of transmission persist despite rapid expansion of ART. Dried blood spot samples from cART-naive participants from two rounds of an annual population-based HIV surveillance program in rural KwaZulu-Natal were tested for HIV RNA, and samples with HIV RNA >10,000 copies/ml were genotyped for drug resistance. The 2009 surveillance of drug resistance mutation (SDRM) list was used for drug resistance interpretation. The data were added to previously published data from the same program, and the chi(2) test for trend was used to test for trend in estimated prevalence of any TDR. Seven hundred and one participants' data were analyzed: 67 (2010), 381 (2011), and 253 (2012). No TDR was detected in 2010. Years 2011 and 2012 had 18 participants with SDRMs 4.7% and 7.1%, respectively (p = .02, chi(2) test for trend). The nonnucleoside reverse transcriptase inhibitor mutation, K103N, was the most common mutation, occurring in 27 (3.8%) of the participants, while nucleoside reverse transcriptase inhibitor (NRTI) SDRMs were detected in 10 (1.4%) of the participants, of whom eight had only a single NRTI SDRM. The increase in levels of drug resistance observed in this population could be a signal of increasing transmission of drug-resistant HIV. Thus, continued surveillance is critical to inform public health policies around HIV treatment and prevention. PMID- 27002372 TI - A comparison of direct and iterative finite element inversion techniques in dynamic elastography. AB - As part of tissue elasticity imaging or elastography, an inverse problem needs to be solved to find the elasticity distribution from the measured displacements. The finite element method (FEM) is a common method for solving the inverse problem in dynamic elastography. This problem has been solved with both direct and iterative FEM schemes. Each of these methods has its own advantages and disadvantages which are examined in this paper. Choosing the data resolution and the excitation frequency are critical for achieving the best estimation of the tissue elasticity in FEM methods. In this paper we investigate the performance of both direct and iterative FEMs for different ranges of excitation frequency. A new form of iterative method is suggested here which requires a lower mesh density compared to the original form. Also two forms of the direct method are compared in this paper: one using the exact fit for derivatives calculation and the other using the least squares fit. We also perform a study on the spatial resolution of these methods using simulations. The comparison is also validated using a phantom experiment. The results suggest that the direct method with least squares fit is more robust to noise compared to other methods but has slightly lower resolution results. For example, for the homogenous region with 20 dB noise added to the data, the RMS error for the direct method with least squares fit is approximately half of the iterative method. It was observed that the ratio of voxel size to the wavelength should be within a specific range for the results to be reliable. For example for the direct method with least squares fit, for the case of 20 dB noise level, this ratio should be between 0.1 to 0.2. On balance, considering the much higher computational cost of the iterative method, the dependency of the iterative method on the initial guess, and the greater robustness of the direct method to noise, we suggest using the direct method with least squares fit for linear elasticity cases. PMID- 27002374 TI - Revision Surgery for "Real" Recurrent Lumbar Disk Herniation: A Systematic Review. AB - STUDY DESIGN: A systematic review. OBJECTIVE: To systematically review the previous literature regarding revision surgery for real recurrent lumbar disk herniation. SUMMARY OF BACKGROUND DATA: "Real" recurrent lumbar disk herniation means the presence of herniated disk material at the same level and side as the primary disk herniation. If conservative treatment fails, revision surgery, a major concern, is indicated. It is important for both patients and spine surgeons to understand epidemiology trends and outcomes of revision surgery for real recurrent lumbar disk herniation (real-RLDH). METHODS: The electronic databases PubMed, the Cochrane library, and EMBASE were queried for English articles regarding revision surgery for real-RLDH, published between January 1980 and May 2014. The incidence, interval between primary and revision surgery, risk factors, surgery type, complications, and clinical outcomes of revision surgery for real RLDH were summarized. RESULTS: The reported incidence of revision surgery, specifically for real-RLDH, lies between 1.4% and 11.4%. The complication rate is reported between 0% and 34.6%, with dural tear being the most common complication. Previous studies revealed that satisfactory or successful clinical outcome was achieved in 60%-100% of patients after revision surgery for real RLDH. Several studies reported similar clinical outcomes between primary and revision surgery. CONCLUSIONS: The incidence of revision surgery for real-RLDH is relatively low. It is essential to pay careful attention to prevent a dural tear. Patients may expect clinical outcomes similar to those following primary discectomy. PMID- 27002375 TI - Minimally Invasive Spinopelvic Fixation for Unstable Bilateral Sacral Fractures. AB - STUDY DESIGN: Retrospective case series. OBJECTIVE: We present a minimally invasive spinopelvic fixation technique for unstable bilateral sacral fractures and describe a technical report. SUMMARY OF BACKGROUND DATA: Unstable sacral fractures are severe injuries with high mortality and morbidity due to pain and malunion. Galveston technique is useful for rigid fixation of an unstable sacral fracture. However, wound-related complications with this technique have been relatively common because of extensive contusion of the skin or poor blood supply after embolization. MATERIALS AND METHODS: There were 34 patients with unstable pelvic fractures between 2005 and 2012. We performed conventional open surgery between 2005 and 2009. Minimally invasive spinopelvic fixation was performed between 2009 and 2012. Minimally invasive technique needs 4 small, lateral incisions for percutaneous lumbar pedicle screw insertion. We pushed a pure titanium rod into the paravertebral muscle. RESULTS: The average surgical time was 345 minutes in the conventional fixation and 208 minutes with the minimally invasive fixation. The average intraoperative bleeding was 520 mL in the conventional fixation and 290 mL in minimally invasive fixation. When comparing deep wound infection, 3 of 8 (38%) patients who received conventional fixation had methicillin-resistant Staphylococcus aureus infections, whereas nobody who received the minimally invasive fixation acquired infection. Bony union was achieved in 15 of the 16 patients. CONCLUSIONS: In this study, minimally invasive spinopelvic fixation required a shorter surgical time, incurred less bleeding, and had a lower infection rate than fixation with the conventional Galveston technique. PMID- 27002369 TI - Current status of new tuberculosis vaccine in children. AB - Pediatric tuberculosis contributes significantly to the burden of TB disease worldwide. In order to achieve the goal of eliminating TB by 2050, an effective TB vaccine is urgently needed to prevent TB transmission in children. BCG vaccination can protect children from the severe types of TB such as TB meningitis and miliary TB, while its efficacy against pediatric pulmonary TB ranged from no protection to very high protection. In recent decades, multiple new vaccine candidates have been developed, and shown encouraging safety and immunogenicity in the preclinical experiments. However, the limited data on protective efficacy in infants evaluated by clinical trials has been disappointing, an example being MVA85A. To date, no vaccine has been shown to be clinically safer and more effective than the presently licensed BCG vaccine. Hence, before a new vaccine is developed with more promising efficacy, we must reconsider how to better use the current BCG vaccine to maximize its effectiveness in children. PMID- 27002376 TI - Unilateral Extraforaminal Lumbar Interbody Fusion (ELIF): Surgical Technique and Clinical Outcome in 107 Patients. AB - STUDY DESIGN: Description of the technique and retrospective study of patients treated with unilateral extraforaminal lumbar interbody fusion (ELIF) for degenerative lumbar spinal disorders. OBJECTIVE: To investigate clinical and radiologic outcome of patients treated with unilateral ELIF. SUMMARY OF BACKGROUND DATA: Lumbar interbody fusion is the classic treatment for higher grades of degenerative disk disease or lumbar segment instability and is performed by posterior (PLIF), posterolateral, or anterior (ALIF) approaches. Those techniques are well established with known limitations and complications. Today, minimally invasive procedures generate more interest especially in terms of muscle damage to achieve better functional outcome. We introduce a unilateral extraforaminal fusion technique which respects neural as well as muscle structures aiming to preserve function. METHODS: Intraoperative and perioperative data, neurological status, Oswestry Disability Index, the Visual Analogue Scale for leg and back pain, and patient satisfaction were investigated preoperatively and at latest follow-up. Fusion status was controlled by x-ray and CT scans at a 6 months' follow-up investigation. RESULTS: A total of 107 patients [female/male: 67/40; average age, 52.8 (+/- 13.8) y] were included at a maximum of 31(+/- 9.4) months. Complications occurred in 4% of patients. Transient radicular pain was investigated in 16 patients. The Oswestry Disability Index and the Visual Analogue Scale for back and leg pain improved significantly. Patients showed a short hospital stay and high percentage of return to work ratio (70%). Fusion was achieved in 97% of patients. CONCLUSIONS: The unilateral ELIF fusion technique demonstrates encouraging clinical and radiologic midterm outcome that for some indications is comparable with established fusion techniques. PMID- 27002377 TI - A genome-wide study of lipid response to fenofibrate in Caucasians: a combined analysis of the GOLDN and ACCORD studies. AB - BACKGROUND: Fibrates are commonly prescribed for hypertriglyceridemia, but they also lower LDL cholesterol and increase HDL cholesterol. Large interindividual variations in lipid response suggest that some patients may benefit more than others and genetic studies could help identify such patients. METHODS: We carried out the first genome-wide association study of lipid response to fenofibrate using data from two well-characterized clinical trials: the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study. Genome-wide association study data from both studies were imputed to the 1000 Genomes CEU reference panel (phase 1). Lipid response was modeled as the log ratio of the post-treatment lipid level to the pretreatment level. Linear mixed models (GOLDN, N=813 from 173 families) and linear regression models (ACCORD, N=781) adjusted for pretreatment lipid level, demographic variables, clinical covariates, and ancestry were used to evaluate the association of genetic markers with lipid response. Among Caucasians, the results were combined using inverse-variance weighted fixed effects meta-analyses. The main findings from the meta-analyses were examined in other ethnic groups from the HyperTG study (N=267 Hispanics) and ACCORD (N=83 Hispanics, 138 African Americans). RESULTS: A known lipid locus harboring the pre B-cell leukemia homeobox 4 (PBX4) gene on chromosome 19 is important for LDL cholesterol response to fenofibrate (smallest P=1.5*10). The main results replicated with nominal statistical significance in Hispanics from ACCORD (P<0.05). CONCLUSION: Future research should evaluate the usefulness of this locus to refine clinical strategies for lipid-lowering treatments. PMID- 27002378 TI - Electrical Transport and Network Percolation in Graphene and Boron Nitride Mixed Platelet Structures. AB - Percolating network of mixed 2D nanomaterials (2DNs) can leverage the unique electronic structures of different 2DNs, their interfacial doping, manipulable conduction pathways, and local traps. Here, we report on the percolation mechanism and electro-capacitive transport pathways of mixed-platelet network of hexagonal boron nitride (hBN) and reduced graphene oxide (rGO), two isostructural and isoelectronic 2DNs. The transport mechanism is explained in terms of electron hopping through isolated hBN defect traps between rGO (possibly via electron tunneling/hopping through "funneling" points). With optical bandgaps of 4.57 and 4.08 eV for the hBN-domains and 2.18 eV for the rGO domains, the network of hBN with rGO exhibits Poole-Frenkel emission-based transport with mean hopping gap of 1.12 nm (~hBN trilayer) and an activation barrier of ~15 +/- 0.7 meV. Further, hBN (1.7 pF) has a 6-fold lower capacitance than 1:1 hBN:rGO, which has a resistance 2 orders of magnitude higher than that of rGO (1.46 MOmega). These carrier transport results can be applied to other multi-2DN networks for development of next-generation functional 2D-devices. PMID- 27002379 TI - Library-Aided Probing of Linker Determinants in Hybrid Photoreceptors. AB - Signaling proteins comprise interaction and effector modules connected by linkers. Throughout evolution, these recurring modules have multiply been recombined to produce the present-day plethora of signaling proteins. Likewise, modular recombination lends itself to the engineering of hybrid signal receptors, whose functionality hinges on linker topology, sequence, and length. Often, numerous linkers must be assessed to obtain functional receptors. To expedite linker optimization, we devised the PATCHY strategy (primer-aided truncation for the creation of hybrid proteins) for the facile construction of hybrid gene libraries with defined linker distributions. Empowered by PATCHY, we engineered photoreceptors whose signal response was governed by linker length: whereas blue light-repressed variants possessed linkers of 7n or 7n+5 residues, variants with 7n+1 residues were blue-light-activated. Related natural receptors predominantly displayed linker lengths of 7n and 7n+5 residues but rarely of 7n+1 residues. PATCHY efficiently explores linker sequence space to yield functional hybrid proteins including variants transcending the natural repertoire of signaling proteins. PMID- 27002380 TI - Troubles in the Systematic Prediction of Transition Metal Thermochemistry with Contemporary Out-of-the-Box Methods. AB - The recently developed DLPNO-CCSD(T) method and seven popular DFT functionals (B3LYP, M06, M06L, PBE, PBE0, TPSS, and TPSSh) with and without an empirical dispersion term have been tested to reproduce 111 gas phase reaction enthalpies involving 11 different transition metals. Our calculations, corrected for both relativistic effects and basis set incompleteness, indicate that most of the methods applied with default settings perform with acceptable accuracy on average. Nevertheless, our calculations also evidenced unexpected and nonsystematic large deviations for specific cases. For group 12 metals (Zn, Cd, Hg), most of the methods provided mean unsigned errors (MUE) less than 5.0 kcal/mol, with DLPNO-CCSD(T) and PBE methods performing excellently (MUE lower 2.0 kcal/mol). Problems started with group 4 metals (Ti and Zr). The best performer for Zr complexes with MUE of 1.8 kcal/mol, PBE0-D3, provides MUE larger than 8 kcal/mol for Ti. DLPNO-CCSD(T) provides a reasonable MUE of 3.3 kcal/mol for Ti reactions but gives MUE a larger than 14.4 kcal/mol for Zr complexes, with all the larger deviations for reactions involving ZrF4. Large and nonsystematic errors have been obtained for group 6 metals (Mo and W), for eight reactions containing Fe, Cu, Nb, and Re complexes. Finally, for the whole set of 111 reactions, the DLPNO-CCSD(T), B3LYP-D3, and PBE0-D3 methods turned out to be the best performers, all providing MUE below 5.0 kcal/mol. Since DFT results cannot be systematically improved and large nonsystematic deviations of 20-30 kcal/mol were obtained even for best performers, our results indicate that current DFT methods are still unable to provide robust predictions in transition metal thermochemistry, at least for the functionals explored in this work. The same conclusion holds for both DLPNO-CCSD(T) and canonical CCSD(T) methods when used entirely as out-of-the-box. However, if careful investigation of core correlation is performed, relativistic effects are properly included and the quality of the reference wave function is properly checked, CCSD(T) methods can still provide good quality results that might even be used to validate DFT methods due to paucity of accurate thermodynamic data for realistic-sized transition metal complexes. PMID- 27002381 TI - La3N@C92: An Endohedral Metallofullerene Governed by Kinetic Factors? AB - Different structures have been proposed so far for the C92 isomer that encapsulates M3N (M = La, Ce, Pr). We show here that the electrochemical properties of the predicted most abundant (thermodynamic) isomer for La3N@C92 does not agree with experiment. After a systematic search within the huge number of possible C92 isomers, we propose other candidates with larger electrochemical gaps for La3N@C92 before its structure could be finally determined by X-ray crystallography. We do not discard that the thermodynamic isomer could be detected in future experiments though. PMID- 27002382 TI - Influence of Birch Bark Triterpenes on Keratinocytes and Fibroblasts from Diabetic and Nondiabetic Donors. AB - Impaired wound healing is one of the main risk factors associated with diabetes mellitus. Few options are available to treat diabetic wounds, and therefore efficient remedies are urgently needed. An interesting option might be an extract of birch bark (TE) that has been clinically proven to accelerate acute wound healing. We investigated the effects of TE and its main components betulin and lupeol in cultured normal keratinocytes and dermal fibroblasts from diabetic and nondiabetic donors. These in vitro models can provide insights into possible beneficial effects in wound healing. TE and betulin treatment led to increased mRNA levels of chemokines, pro-inflammatory cytokines, and mediators important in wound healing, e.g., IL-6, TNFalpha, IL-8, and RANTES. We observed a pronounced upregulation of MIF, IL-8, and RANTES on the protein level. Furthermore, a shape change of the actin cytoskeleton was seen in keratinocytes and fibroblasts, and the Rho-GTPases and p38-MAPK were found to be activated in keratinocytes. On the basis of our results, TE is worthy of further study as a potential option to influence wound-healing processes under diabetic conditions. These first insights need to be confirmed by clinical studies with diabetic patients. PMID- 27002383 TI - The value of magnetic resonance imaging in investigating complex atypical hyperplasia of the endometrium. AB - BACKGROUND: Magnetic resonance imaging (MRI) has been recommended to rule out myometrial invasion or distant metastasis before treatment for complex atypical hyperplasia (CAH). This study aimed to evaluate whether preoperative MRI in patients diagnosed with CAH on initial biopsy will have any impact on their management. METHODS: A retrospective study of women diagnosed with CAH on initial endometrial biopsy that subsequently had hysterectomies. Definitive diagnosis was established at histology of the hysterectomy specimens and compared with preoperative MRI findings. RESULTS: Preoperative MRI scan was performed in 33 of 106 patients and myometrial invasion was reported in 12 patients with final histology diagnosing endometrial cancer in 10 patients. Twenty-one out of 33 cases were reported as no invasion on MRI but nine patients were confirmed with endometrial cancer on histology. Of the thirty-three patients diagnosed with endometrial cancer, twenty had stage 1a cancer, eight had stage 1b and five had stage 2 cancer. Twenty-seven patients had grade 1 and six patients had grade 2 cancer with no high-grade subtypes. CONCLUSIONS: In our series, we found that MRI had no value in the management of CAH. Thirty-three endometrioid endometrial cancers (31%) were identified and we found no high-risk subtypes, and simple hysterectomy and bilateral salpingo-oophorectomy would be performed and the few stage 2 cases diagnosed were microscopic and would not have been diagnosed on MRI. PMID- 27002384 TI - Current trends and controversies in reproductive surgery. AB - Even in the context of the expansion of assisted reproductive technologies (ART), reproductive surgery continues to fulfill its deserved place in the arsenal of fertility treatments. Rather than being competitive, these two avenues of treatment can optimize fertility care when utilized as an adjunct to one another. Surgical indications and techniques in modern reproductive surgery continue to evolve based on new information about the effects of pelvic pathology on infertility and new technology. This review aims to disentangle some of the common clinical dilemmas facing reproductive specialists in regard to the effect of benign gynecologic pathology on fertility and the relevance of surgical intervention in enhancing or preserving fertility in women. To this end, we focus on the management of intramural myomata, adenomyosis, ovarian and peritoneal endometriosis and teratomas in women of reproductive age. In addition, we also review the role of recently developed techniques in the field of ovarian tissue preservation as well as uterine transplantation. PMID- 27002385 TI - Changes in Strength, Power, and Speed Across a Season in English County Cricketers. AB - PURPOSE: Previous research has investigated changes in athletes' strength, power, and speed performances across the competitive season of many sports, although this has not been explored in cricketers. The aim of this study was to investigate changes in lower-body strength and jump and sprint performances across an English county cricket season. METHODS: Male cricketers (N = 12; age 24.4 +/- 2.3 y, body mass 84.3 +/- 9.9 kg, height 184.1 +/- 8.1 cm) performed countermovement jumps (CMJs) and 20-m sprints on 4 separate occasions and back squat strength testing on 3 separate occasions across a competitive season. RESULTS: Both absolute (12.9%, P = .005, effect size [ES] = 0.53) and relative lower-body strength (15.8%, P = .004, ES = 0.69) and CMJ height (5.3%, P = .037, ES = 0.42) improved significantly over the preseason training period, although no significant change (1.7%, P > .05) in sprint performance was observed. In contrast, absolute (14.3%, P = .001, ES = 0.72) and relative strength (15.0%, P = .001, ES = 0.77), CMJ height (4.2%, P = .023, ES = 0.40), and sprint performance (3.8%, P = .012, ES = 0.94) declined significantly across the season. CONCLUSIONS: The results of this study show that neither the demands of the competitive cricket season nor current in-season training practices provide a sufficient stimulus to maintain strength, jump, and sprint performances in these cricketers. Therefore, coaches should implement a more-frequent, higher-load strength-training program across the competitive cricket season. PMID- 27002386 TI - Crystal Phase- and Orientation-Dependent Electrical Transport Properties of InAs Nanowires. AB - We report a systematic study on the correlation of the electrical transport properties with the crystal phase and orientation of single-crystal InAs nanowires (NWs) grown by molecular-beam epitaxy. A new method is developed to allow the same InAs NW to be used for both the electrical measurements and transmission electron microscopy characterization. We find both the crystal phase, wurtzite (WZ) or zinc-blende (ZB), and the orientation of the InAs NWs remarkably affect the electronic properties of the field-effect transistors based on these NWs, such as the threshold voltage (VT), ON-OFF ratio, subthreshold swing (SS) and effective barrier height at the off-state (PhiOFF). The SS increases while VT, ON-OFF ratio, and PhiOFF decrease one by one in the sequence of WZ ?0001?, ZB ?131?, ZB ?332?, ZB ?121?, and ZB ?011?. The WZ InAs NWs have obvious smaller field-effect mobility, conductivities, and electron concentration at VBG = 0 V than the ZB InAs NWs, while these parameters are not sensitive to the orientation of the ZB InAs NWs. We also find the diameter ranging from 12 to 33 nm shows much less effect than the crystal phase and orientation on the electrical transport properties of the InAs NWs. The good ohmic contact between InAs NWs and metal remains regardless of the variation of the crystal phase and orientation through temperature-dependent measurements. Our work deepens the understanding of the structure-dependent electrical transport properties of InAs NWs and provides a potential way to tailor the device properties by controlling the crystal phase and orientation of the NWs. PMID- 27002388 TI - In silico prediction of long intergenic non-coding RNAs in sheep. AB - Long non-coding RNAs (lncRNAs) are transcribed RNA molecules >200 nucleotides in length that do not encode proteins and serve as key regulators of diverse biological processes. Recently, thousands of long intergenic non-coding RNAs (lincRNAs), a type of lncRNAs, have been identified in mammalians using massive parallel large sequencing technologies. The availability of the genome sequence of sheep (Ovis aries) has allowed us genomic prediction of non-coding RNAs. This is the first study to identify lincRNAs using RNA-seq data of eight different tissues of sheep, including brain, heart, kidney, liver, lung, ovary, skin, and white adipose. A computational pipeline was employed to characterize 325 putative lincRNAs with high confidence from eight important tissues of sheep using different criteria such as GC content, exon number, gene length, co-expression analysis, stability, and tissue-specific scores. Sixty-four putative lincRNAs displayed tissues-specific expression. The highest number of tissues-specific lincRNAs was found in skin and brain. All novel lincRNAs that aligned to the human and mouse lincRNAs had conserved synteny. These closest protein-coding genes were enriched in 11 significant GO terms such as limb development, appendage development, striated muscle tissue development, and multicellular organismal development. The findings reported here have important implications for the study of sheep genome. PMID- 27002389 TI - Breast hamartoma: A report of 14 cases of an under-recognized and under-reported entity. AB - OBJECTIVES: Mammary hamartoma is a rare benign lesion accounting for approximately 4.8% of all benign breast masses. It is often underdiagnosed and therefore is underreported mostly due to lack of awareness of the characteristic clinical and histological features. Raising awareness of this poorly recognized benign entity is of utmost significance as it clinically mimics other breast tumors including both benign and malignant ones. This study is to report and present our experience of breast hamartomas from Johns Hopkins Aramco Healthcare in the Eastern province of Saudi Arabia from which there have not been previous studies in literature. METHOD: A retrospective review of our pathology files was done from 1994 to 2014 for cases diagnosed as breast hamartoma during this 20 year period. RESULTS: A total of 14 cases with diagnosis of breast hamartoma were identified in our institute. Histologically the lesion is mostly sharply demarcated showing a mixture of varying proportions of fibrous, adipose, and glandular tissue. 13 cases were seen in females (93%) and only one rare occurrence in a male patient (7%). The age ranges quite vastly from 18 to 51 years (mean 33 years). Two-third of these lesions were seen involving the right breast (9 cases/64.3%) and only one-third in the left side (5 cases/35.7%). 13 out of 14 patients had a well circumscribed lesion (92.9%) while only 1 case showed irregular borders (7.1%). The size varied from 1.4 to 9.5cm. Three cases (21.4%) showed evidence of myoid differentiation, a histopathologic variance which is important to identify however has no clinical significance. 3 cases had associated epithelial ductal hyperplasia of the usual type varying from mild (2 cases) to moderate (1 case); with two of these cases exhibiting additional features of fibrocystic mastopathy including adenosis, apocrine metaplasia, and cyst formation. None of our cases showed any malignancy or pseudoangiomatous stroma hyperplasia (PASH). PMID- 27002390 TI - Marine Metabolites Modulating CB Receptors and TRP Channels. AB - Transient receptor potential channels and cannabinoid receptors are deputed to the regulation of sensory, homeostatic, and inflammatory events in the human organism. Therefore, their modulation promises to have relevant applications in important therapeutic areas such as inflammation, pain, and cancer. This review summarizes the contribution of marine research in this relatively young field, highlighting the potential of the chemodiversity carried by marine natural products in the discovery of new ligands. PMID- 27002387 TI - Prenatal fat exposure and hypothalamic PPAR beta/delta: Possible relationship to increased neurogenesis of orexigenic peptide neurons. AB - Gestational exposure to a fat-rich diet, while elevating maternal circulating fatty acids, increases in the offspring's hypothalamus and amygdala the proliferation and density of neurons that express neuropeptides known to stimulate consummatory behavior. To understand the relationship between these phenomena, this study examined in the brain of postnatal offspring (day 15) the effect of prenatal fat exposure on the transcription factor, peroxisome proliferator-activated receptor (PPAR) beta/delta, which is sensitive to fatty acids, and the relationship of PPAR beta/delta to the orexigenic neuropeptides, orexin, melanin-concentrating hormone, and enkephalin. Prenatal exposure to a fat rich diet compared to low-fat chow increased the density of cells immunoreactive for PPAR beta/delta in the hypothalamic paraventricular nucleus (PVN), perifornical lateral hypothalamus (PFLH), and central nucleus of the amygdala (CeA), but not the hypothalamic arcuate nucleus or basolateral amygdaloid nucleus. It also increased co-labeling of PPAR beta/delta with the cell proliferation marker, BrdU, or neuronal marker, NeuN, and the triple labeling of PPAR beta/delta with BrdU plus NeuN, indicating an increase in proliferation and density of new PPAR beta/delta neurons. Prenatal fat exposure stimulated the double-labeling of PPAR beta/delta with orexin or melanin-concentrating hormone in the PFLH and enkephalin in the PVN and CeA and also triple-labeling of PPAR beta/delta with BrdU and these neuropeptides, indicating that dietary fat increases the genesis of PPAR beta/delta neurons that produce these peptides. These findings demonstrate a close anatomical relationship between PPAR beta/delta and the increased proliferation and density of peptide-expressing neurons in the hypothalamus and amygdala of fat-exposed offspring. PMID- 27002391 TI - Effect of Ginger and Turmeric Rhizomes on Inflammatory Cytokines Levels and Enzyme Activities of Cholinergic and Purinergic Systems in Hypertensive Rats. AB - Inflammation exerts a crucial pathogenic role in the development of hypertension. Hence, the aim of the present study was to investigate the effects of ginger (Zingiber officinale) and turmeric (Curcuma longa) on enzyme activities of purinergic and cholinergic systems as well as inflammatory cytokine levels in Nomega-nitro-L-arginine methyl ester hydrochloride-induced hypertensive rats. The rats were divided into seven groups (n = 10); groups 1-3 included normotensive control rats, hypertensive (Nomega-nitro-L-arginine methyl ester hydrochloride) rats, and hypertensive control rats treated with atenolol (an antihypertensive drug), while groups 4 and 5 included normotensive and hypertensive (Nomega-nitro L-arginine methyl ester hydrochloride) rats treated with 4 % supplementation of turmeric, respectively, and groups 6 and 7 included normotensive and hypertensive rats treated with 4 % supplementation of ginger, respectively. The animals were induced with hypertension by oral administration of Nomega-nitro-L-arginine methyl ester hydrochloride, 40 mg/kg body weight. The results revealed a significant increase in ATP and ADP hydrolysis, adenosine deaminase, and acetylcholinesterase activities in lymphocytes from Nomega-nitro-L-arginine methyl ester hydrochloride hypertensive rats when compared with the control rats. In addition, an increase in serum butyrylcholinesterase activity and proinflammatory cytokines (interleukin-1 and - 6, interferon-gamma, and tumor necrosis factor-alpha) with a concomitant decrease in anti-inflammatory cytokines (interleukin-10) was observed in Nomega-nitro-L-arginine methyl ester hydrochloride hypertensive rats. However, dietary supplementation of both rhizomes was efficient in preventing these alterations in hypertensive rats by decreasing ATP hydrolysis, acetylcholinesterase, and butyrylcholinesterase activities and proinflammatory cytokines in hypertensive rats. Thus, these activities could suggest a possible insight about the protective mechanisms of the rhizomes against hypertension-related inflammation. PMID- 27002392 TI - New Cytotoxic Tigliane Diterpenoids from Croton caudatus. AB - Three new tigliane-type diterpenoids were isolated from the methanolic extract of the twigs and leaves of Croton caudatus, trivially named crotusins A-C (1-3). The structures of compounds 1-3 were elucidated on the basis of extensive spectral methods. These new compounds were highly oxygenated and heavily substituted. Cytotoxic activity against five human tumor cell lines was assessed for compounds 1-3 of which compound 3 showed significant inhibitory activity with IC50 values ranging from 0.49 to 4.19 uM against these cells, while crotusins A and B exhibited moderate activity. PMID- 27002393 TI - (-)-Hinokinin Induces G2/M Arrest and Contributes to the Antiproliferative Effects of Doxorubicin in Breast Cancer Cells. AB - Breast cancer incidence rises worldwide and new chemotherapeutical strategies have been investigated to overcome chemoresistance. (-)-Hinokinin is a dibenzylbutyrolactone lignan derived from the partial synthesis of (-)-cubebin extracted from Piper cubeba seeds. Biological effects of dibenzylbutyrolactone lignans include antiviral, antitumor, anti-inflammatory, and trypanocidal activities. In the present study, we evaluated the ability of (-)-hinokinin to modulate the antiproliferative effects of doxorubicin intumoral (MCF-7 and SKBR 3) and normal (MCF-10 A) breast cell lines. Treatment with (-)-hinokinin did not affect the cellular proliferation or contribute to the antitproliferative effects of doxorubicin in MCF-10 A cells. After 24 and 48 hours of treatment with (-) hinokinin, MCF-7 and SKBR-3 were accumulated in G2/M and, when combined with doxorubicin, (-)-hinokinin contributed to the antiproliferative effects of this chemotherapic by modulation of the cyclin-dependent kinase inhibitor 1. Apoptotic cell death was observed in response to (-)-hinokinin alone in MCF-7, but not in SKBR-3 even 72 hours after treatment. In MCF-7, doxorubicin-induced apoptosis was not increased by (-)-hinokinin. The findings of the present study suggest (-) hinokinin as an antiproliferative agent that contributes to the effects of doxorubicin. (-)-Hinokinin modulates apoptotic cell death via the molecular regulation of the cell cycle and apoptotic control genes, but the cellular genetic background directly affects the cell fate decision in response to treatment. PMID- 27002394 TI - New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility. AB - Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10-3 and 3 * 10-8 M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index (< 0.20) was found in both formulations. Formulation 1 was selected to test in vitro drug release because it was superior in terms of encapsulation efficiency (62 %) and loading capacity (32 %). The solubility of curcumin was increased ca. 415 and 150 times with respect to the unformulated drug, respectively, for formulation 1 and formulation 2. The release of curcumin from the nanoparticles showed an interesting prolonged and sustained release profile. PMID- 27002395 TI - Development of Blood-Brain Barrier Permeable Nanoparticles as Potential Carriers for Salvianolic Acid B to CNS. AB - The blood-brain barrier hinders the passage of systemically delivered therapeutics and the brain extracellular matrix limits the distribution and durability of locally delivered agents. Drug-loaded nanocarriers represent a promising strategy to overcome these barriers and address specific drug delivery challenges due to their small size and versatile design. We synthetized [fluorescent poly(ethyl-cyanoacrylate) nanoparticles coated with Tween 80 by an emulsion polymerization method to target and reach the brain after intravenous and intraperitoneal administration. Nanoparticles were characterized in terms of dimensional analysis, polydispersity and zeta potential (zeta-potential), morphology, encapsulation efficacy, and loading capacity. After intracerebral injection in healthy rats, nanoparticles were distributed within the injected hemisphere and mainly interacted with microglial cells, presumably involved in their clearance by phagocytosis. Furthermore, nanoparticles were able to pass the blood-brain barrier after systemic administration in rats, and the lack of toxicity in C57/B6 mice chronically administered was highlighted. The data obtained helped to clarify the nanoparticles distribution, accumulation, fate, and toxicity into the brain. The selected nanoparticles may represent a biocompatible promising carrier to be further investigated as brain delivery systems. Salvianolic acid B from Salvia miltiorrhiza is a promising molecule in the protection of degeneration in several animal models by various biological mechanisms, but its poor chemical stability and low bioavailability limits its clinical application for central nervous system neuronal injury and degeneration. Nanoparticles were loaded with salvianolic acid B obtaining an encapsulation efficacy and loading capacities of 98.70 % +/- 0.45 and 53.3 % +/- 0.24, respectively. They were suitable for parental administration because their mean diameter was smaller than 300 nm, with a polydispersity of 0.04 +/- 0.03, and a zeta-potential of - 8.38 mV +/- 3.87. The in vitro release of salvianolic acid B from the nanoparticles was sustained and prolonged during 8 h, suitable for a promising clinical application. PMID- 27002396 TI - Anti-MMP-2 Activity and Skin-Penetrating Capability of the Chemical Constituents from Rhodiola rosea. AB - Based on the significant inhibitory activity toward matrix metalloproteinase-2 and collagenase noticed in preliminary studies, crude extracts of Rhodiola rosea were partitioned and chromatographed sequentially to afford three new compounds, 1,2,3,6-tetra-O-galloyl-4-O-p-hydroxybenzoyl-beta-D-glucopyranoside (1), (E) creoside I (2), and (R,Z)-2-methylhept-2-ene-1,6-diol (3), along with twenty-four known compounds (4-27). Their structures were determined by spectroscopic data analyses. All isolated compounds were subjected to bioactivity assays. In these, 1 specifically inhibited matrix metalloproteinase-2 activity with an IC50 value of 16.3 +/- 1.6 uM, while its analogue 1,2,3,6-tetra-O-galloyl-beta-D glucopyranonoside (17) inhibited matrix metalloproteinase-2 with an IC50 value of 23.0 +/- 4.8 uM. In the collagenase activity assay, the inhibitory effects of 1 and 17 at concentrations of both 20 and 40 uM were more potent than those of the positive control, 1,10-phenanthroline. In order to realize whether 17 could penetrate from the epidermal layer into the basal and dermal layers of the human skin to inhibit the activity of matrix metalloproteinase-2 and collagenase or not, a transdermal penetration test in nude and white mice skins was performed. Penetration percentages of 17 quantified by LC-MS were 27.8 % and 74.8 % in 24 hours, respectively. PMID- 27002397 TI - Antifungal Indole Alkaloids from Winchia calophylla. AB - Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 uM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 uM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 uM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 uM, respectively. PMID- 27002398 TI - Peniphenylanes A-G from the Deep-Sea-Derived Fungus Penicillium fellutanum HDN14 323. AB - Seven new 6-methylsaligenin derivatives, including the trimeric peniphenylanes A B (1-2) and dimeric peniphenylanes C-G (3-7), together with four known biogenetically related compounds (8-11) were discovered from the extract of the deep-sea-derived fungus Penicillium fellutanum HDN14-323. The structures of the new compounds were established through extensive analysis. Their cytotoxic activity against HeLa, HL-60, and HCT-116 cell lines was evaluated, with compound 4 exhibiting the best activity against the HeLa cell line (IC50 = 9.3 uM). PMID- 27002399 TI - Changes in Plasma Lipid Levels and Antioxidant Activities in Rats after Supplementation of Obtusifolin. AB - Obtusifolin, an anthraquinone from Cassia obtusifolia seeds, has been reported to reduce blood lipid levels in diabetic rats induced by streptozocin. However, it remains unclear whether obtusifolin possesses a lipid-lowering effect on hyperlipidemia caused by a high-fat diet. Moreover, hyperlipidemia is known to impair the endothelial function by causing oxidative stress. Therefore, in the present study, we investigated the antidyslipidemic and antioxidant effects of obtusifolin in hyperlipidemic rats induced by a high-fat diet. Rats with oral fat emulsion were used as our hyperlipidemic model. We measured the body weight of the rats, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, as well as nitric oxide, malondialdehyde, and superoxide dismutase. Our results showed that oral obtusifolin application significantly reversed the changes induced by hyperlipidemia in body weight, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Furthermore, obtusifolin treatment increased serum superoxide dismutase and nitric oxide, but reduced malondialdehyde. Collectively, our findings suggest that obtusifolin may improve hyperlipidemia by enhancing antioxidant activity. This study indicates a potential therapeutic importance of obtusifolin for ameliorating lipid dysfunction induced by a high-fat diet. PMID- 27002400 TI - Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae. AB - Sponges are a useful source of bioactive natural products. Members of the family Mycalidae, in particular, have provided a variety of chemical structures including alkaloids, polyketides, terpene endoperoxides, peptides, and lipids. This review highlights the compounds isolated from Mycalid sponges and their associated biological activities. A diverse group of 190 compounds have been reported from over 40 specimens contained in 49 references. Over half of the studies have reported on the biological activities for the compounds isolated. The polyketides, in particular the macrolides, displayed potent cytotoxic activities (< 1 uM), and the alkaloids, in particular the 2,5-disubstituted pyrrole derivatives, were associated with moderate cytotoxic activities (1-20 uM). The pyrrole alkaloids and the cyclic peroxides appear to be phylogenetically restricted to sponges and thus might prove useful when applied to sponge taxonomy. The observed diversity of chemical structures suggests this family makes a good target for targeted biodiscovery projects. PMID- 27002401 TI - Combined LC/UV/MS and NMR Strategies for the Dereplication of Marine Natural Products. AB - Drug discovery from marine natural products has experienced a revival since the beginning of this century. To be successful in this field, rapid dereplication (identification of already known bioactive compounds) is essential in order to assess the chemical novelty of crude extracts and their fractions. Access to the appropriate state-of-the-art analytical instrumentation and to suitable databases is a fundamental requirement in such a task. A brief survey of the most robust LC/UV/MS- and NMR-based approaches employed for marine natural product dereplication is presented alongside a description of the procedures followed to achieve this goal in our research group. PMID- 27002402 TI - Arabidopsis DREB1B in transgenic Salvia miltiorrhiza increased tolerance to drought stress without stunting growth. AB - Multiple stress response genes are controlled by transcription factors in a coordinated manner; therefore, these factors can be used for molecular plant breeding. CBF1/DREB1B, a known stress-inducible gene, was isolated from Arabidopsis thaliana and introduced into Salvia miltiorrhiza under the control of the CaMV35S or RD29A promoter. Under drought stress, relative water content, chlorophyll content, and the net photosynthetic rate were observed to be higher in the transgenic lines than in the wild type (WT). Moreover, O2(-) and H2O2 accumulation was observed to be lower in the transgenic lines. Additional analyses revealed that the AtDREB1B transgenic plants generally displayed lesser malondialdehyde (MDA) but higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities than the WT under drought stress. Quantitative real time polymerase chain reaction of a subset of genes involved in photosynthesis, stress response, carbohydrate metabolism, and cell protection further verified that AtDREB1B could enhance tolerance to drought by activating different downstream DREB/CBF genes in the transgenic plants. Furthermore, no growth inhibition was detected in transgenic S. miltiorrhiza plants that expressed AtDREB1B driven by either the constitutive CaMV35S promoter or the stress inducible RD29A promoter. Together, these results suggest that AtDREB1B is a good candidate gene for increasing drought tolerance in transgenic S. miltiorrhiza. PMID- 27002403 TI - Elsholtzia ciliata (Thunb.) Hylander attenuates renal inflammation and interstitial fibrosis via regulation of TGF-beta and Smad3 expression on unilateral ureteral obstruction rat model. AB - BACKGROUND: Renal interstitial fibrosis is characterized by excessive accumulation of extracellular matrix, which leads to end-stage renal failure. PURPOSE: The aim of this study was to explore the effect of Elsholtzia ciliata (Thunb.) Hylander ethanol extract (ECE) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). STUDY DESIGN: After quantitative analysis of ECE using the high performance liquid chromatography-photodiode array (HPLC PDA) method, an in vitro study was performed to assess the anti-inflammatory and anti-fibrotic effects of ECE, using lipopolysaccharide (LPS) and transforming growth factor-beta (TGF-beta), respectively. METHODS: For in vivo study, all male Sprague Dawley (SD) rats (n=10/group), except for those in the control group, underwent UUO. The rats were orally treated with water (control), captopril (positive control, 200 mg/kg), and ECE (300 and 500 mg/kg) for 14 days. RESULTS: In ECE, luteolin and rosmarinic acid were relatively abundant among the other flavonoids and phenolic acids. ECE treatment ameliorated LPS-induced overexpression of nuclear factor-kappaB, tumor necrosis factor (TNF-alpha), and interleukin-6 and improved oxidative stress in RAW 264.7 cells. Furthermore, ECE treatment suppressed TGF-beta-induced alpha-smooth muscle actin and matrix metalloproteinase 9 expression in human renal mesangial cells. In the UUO model, 14 consecutive days of ECE treatment improved UUO-induced renal damage and attenuated histopathological alterations and interstitial fibrosis. Moreover, the renal expression of TNF-alpha, TGF-beta, and Smad 3 were inhibited by ECE treatment. CONCLUSION: Taken together, the effects of ECE may be mediated by blocking the activation of TGF-beta and inflammatory cytokines, leading subsequently to degradation of the ECM accumulation pathway. Based on these findings, ECE might serve as an improved treatment strategy for renal fibrotic disease. PMID- 27002404 TI - Wedelolactone metabolism in rats through regioselective glucuronidation catalyzed by uridine diphosphate-glucuronosyltransferases 1As (UGT1As). AB - BACKGROUND: Wedelolactone (WEL), a medicinal plant-derived coumestan, has been reported to exhibit a diverse range of pharmacological activities. However, the metabolism and disposition of WEL remain unexplored. PURPOSE: The present study aims to investigate the metabolism of WEL in rats and identify the enzymes responsible for forming major WEL metabolites. METHODS: Plasma, urine, feces, and bile samples were collected before and after 50 mg/kg WEL was orally administered to rats. Metabolites were profiled by ultrahigh performance liquid chromatography/quadrupole time-of-flight mass spectrometry and identified by high performance liquid chromatography-solid-phase extraction-nuclear magnetic resonance spectroscopy. The in vitro WEL glucuronidation activities of human liver microsomes, human kidney microsomes, human intestine microsomes, and 12 recombinant human uridine diphosphate-glucuronosyltransferase (UGT) isoforms were screened. Molecular docking simulation of the interaction between WEL and UGT1A9 was conducted. RESULTS: WEL underwent extensive metabolism, and 17 metabolites were identified. The major metabolic pathways observed were glucuronidation and methylation. Glucuronic acid was preferentially introduced into 5-OH, whereas no obvious regioselectivity was observed in the methylation of 11-OH and 12-OH. Multiple UGTs, including UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10, were involved in forming WEL glucuronides and O-methylated WEL glucuronides. CONCLUSION: The extensive glucuronidation and methylation is responsible for the low oral bioavailability of WEL in rats. UGT1A1 and UGT1A9 were the major enzymes involved in the glucuronidation of WEL and O-methylated WEL. Molecular docking studies revealed that 5-OH was accessible to the catalytic domain of UGT1As; therefore, 5-OH exhibited a high probability of glucuronidation. PMID- 27002405 TI - Protective role of gambogic acid in experimental pulmonary fibrosis in vitro and in vivo. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. The treatment options for IPF are very limited. Gambogic acid (GA) has anticancer effect and anti-proliferative activity which is extracted from a dried yellow resin of the Garcinia hanburyi Hook.f. [Clusiaceae (Guttiferae)] in Southeast Asia. However, the anti-fibrotic activities of GA have not been previously investigated. METHODS: In this study, the effects of GA on TGF-beta1-mediated epithelial-mesenchymal transition (EMT) in A549 cells and endothelial-mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMECs), on the proliferation of human lung fibroblasts (HLF 1) were investigated in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo. RESULTS: In TGF-beta1 stimulated A549 cells, treatment with GA resulted in a reduction of EMT with a decrease in vimentin and p-Smad3 and an increase in E-cadherin instead. In TGF-beta1 stimulated HPMECs, treatment with GA resulted in a reduction of EndoMT with a decrease in vimentin, and an increase in VE-cadherin instead. In the hypoxic HPMECs, treatment with GA reduced Vasohibin-2 (VASH-2), whereas increased VASH-1. In TGF-beta1 stimulated HLF-1, treatment with GA reduced HLF-1 proliferation with a decrease in platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF-2) expressions. In vivo, treatment with GA for 2 weeks resulted in an amelioration of the BLM-induced pulmonary fibrosis in rats with a lower VASH-2. Instead, it was observed a higher VASH-1 expression at early stage of fibrosis at 1 mg/kg, with reductions of the pathological score, collagen deposition, alpha-SMA, PDGF and FGF-2 expressions at fibrotic stage at 0.5 mg/kg and 1 mg/kg. CONCLUSION: In summary, GA reversed EMT and EndoMT, as well as HLF-1 proliferation in vitro and prevented pulmonary fibrosis in vivo by modulating VASH-2/VASH-1 and suppressing the TGF-beta1/Smad3 pathway. PMID- 27002406 TI - Glabridin induces apoptosis and autophagy through JNK1/2 pathway in human hepatoma cells. AB - BACKGROUND: Extensive research results support the use of herbal medicine or natural food to augment therapy for various cancers. Studies have associated glabridin with numerous biological activities, such as regulating energy metabolism and estrogenic, neuroprotective, antiosteoporotic, and skin-whitening activities. HYPOTHESIS/PURPOSE: However, how glabridin affects tumor cell autophagy has not been clearly determined. METHODS: Autophagy is a lysosomal degradation pathway essential for cell survival and tissue homeostasis. In this study, the roles of autophagy and related signaling pathways during glabridin induced autophagy in human liver cancer cells were investigated. Additionally, the molecular mechanism of the anticancer effects of glabridin in human hepatoma cells was investigated. RESULTS: The results revealed that glabridin significantly inhibited cell proliferation in human hepatoma cells. Glabridin induced apoptosis dose-dependently in Huh7 cells through caspase-3, -8, and -9 activation and PARP cleavage. Furthermore, autophagy was detected as early as 12h after exposure to a low dose of glabridin, as indicated by the up-regulated expression of LC3-II and beclin-1 proteins. The inhibition of JNK1/2 and p38 MAPK by specific inhibitors significantly reduced glabridin-induced activation of caspases-3, -8, and -9. Blocking autophagy sensitize the Huh7 cells to apoptosis. CONCLUSION: This study demonstrated for the first time that autophagy occurs earlier than apoptosis does during glabridin-induced apoptosis in human liver cancer cell lines. Glabridin induces Huh7 cell death through apoptosis through the p38 MAPK and JNK1/2 pathways and is a potential chemopreventive agent against human hepatoma. PMID- 27002407 TI - Amygdalin, quackery or cure? AB - BACKGROUND: The cyanogenic diglucoside, amygdalin, has gained high popularity among cancer patients together with, or in place of, conventional therapy. Still, evidence based research on amygdalin is sparse and its benefit controversial. PURPOSE: Since so many cancer patients consume amygdalin, and many clinicians administer it without clear knowledge of its mode of action, current knowledge has been summarized and the pros and cons of its use weighed. METHODS: A retrospective analysis was conducted for amygdalin relevant reports using the PubMed database with the main search term "Amygdalin" or "laetrile", at times combined with "cancer", "patient", "cyanide" or "toxic". We did not exclude any "unwanted" articles. Additionally, internet sources authorized by governmental or national institutions have also been included. SECTIONS: Individual chapters summarize pharmacokinetics, preclinical and clinical studies and toxicity. CONCLUSION: No convincing evidence showing that amygdalin induces rapid, distinct tumor regression in cancer patients, particularly in those with late-stage disease, is apparent. However, there is also no evidence that purified amygdalin, administered in "therapeutic" dosage, causes toxicity. Multiple aspects of amygdalin administration have not yet been adequately explored, making further investigation necessary to evaluate its actual therapeutic potential. PMID- 27002408 TI - An effective identification and quantification method for Ginkgo biloba flavonol glycosides with targeted evaluation of adulterated products. AB - BACKGROUND: Ginkgo biloba L. (Ginkgoaceae) leaf extract is one of the most popular herbal products on the market, as it contains flavone glycosides (>= 24%) and terpene lactones (>= 6%), which are proposed to have significant physiological effects. Unfortunately, the challenging financial climate has resulted in a natural health product market containing adulterated ginkgo products. PURPOSE: 42 ginkgo samples were analyzed to establish an HPLC profile for authentic ginkgo and common ginkgo adulterants, and to develop a method capable of easily detecting adulteration in ginkgo commercial products. METHOD: In this study an efficient and targeted HPLC analysis method was established that is capable of distinguishing flavonol glycosides and aglycones simultaneously for the evaluation of ginkgo powdered extracts (PEs) and finished products in a single, 13 min run. Thirteen ginkgo leaf samples, fifteen standardized powdered extracts, and fourteen commercially available ginkgo products have been analyzed using this new HPLC method. Chromatograms were compared to six standard reference materials: one flavonol glycoside (rutin), three aglycones (quercetin, kaempferol and isorhamnetin), and two isoflavones (genestin and genistein). The quantitative chromatographic data was interpreted by principal component analysis (PCA), which assisted in the detection of unexpected chromatographic features in various adulterated botanical products. RESULTS: Only three of the commercially available ginkgo finished products tested in this study were determined to be authentic, with flavonol glycoside rutin, and aglycones quercetin, kaempferol, and isorhamnetin found to be common adulterants in the ginkgo powdered extract and finished product samples. CONCLUSION: Despite evidence of adulteration in most of the samples, each of the samples discussed herein met most of the current pharmacopeial standards. It is therefore critical that a preliminary evaluation be utilized to detect adulteration in commercial ginkgo products, prior to the acid hydrolysis procedure utilized in the current testing methods. PMID- 27002409 TI - Osteomeles schwerinae extracts inhibits the binding to receptors of advanced glycation end products and TGF-beta1 expression in mesangial cells under diabetic conditions. AB - BACKGROUND: Osteomeles schwerinae C. K. Schneid. (Rosaceae, OSSC) is a medicinal plant traditionally used to treat various diseases in Asia. The chemical constituents of OSSC have an inhibitory effect on aldose reductase activity, which has been implicated in the pathogenesis of diabetic complications. However, the protective effects of the pharmacological activity and potential mechanisms in diabetic nephropathy are still not known. OBJECTIVE: In the present study, OSSC extracts and major compounds were examined for their effects on binding to the receptors of advanced glycation end products (RAGE) and on transforming growth factor-beta1 (TGF-beta1) expression-related signal mechanisms in mouse glomerular mesangial cells (GMCs). MATERIALS AND METHODS: A simple, rapid and efficient method was developed for the simultaneous determination of the marker compounds in the ethanol extract of the leaves and twigs of OSSC using HPLC-diode array detector (DAD). In this study, we determined the effects of OSSC extract and hyperoside on AGE and RAGE binding, and studied the mechanism of OSSC extract effects on AGE-bovine serum albumin (BSA)-treated GMCs. GMCs overexpressing human RAGE were cultured in AGE-BSA labeled with Alexa 488, and OSSC extract. AGE/RAGE binding were measured using fluorescence (excitation 485 nm/emission 528 nm). TGF beta1 protein expression levels were determined by western blot analyses. RESULTS: OSSC extracts of leaves and twigs inhibited on AGE/RAGE binding and TGF beta1 protein expression in a dose-dependent manner in GMCs. Furthermore, OSSC extracts reduced the effects on AGE-BSA-induced reactive oxidative species (ROS) formation and nuclear translocalization of transcription factor NF-kappaB. OSSC extracts inhibited phosphorylation of extracellular signal-regulated protein kinases1/2 (ERK1/2), p38 mitogen-activated protein kinases (p38MAPK), and IkappaB. Hyperoside also inhibited AGE/RAGE binding and ROS formation, and reduced TGF-beta1 expression and IkB phosphorylation. CONCLUSIONS: OSSC extracts and hyperoside may attenuate AGE/RAGE binding and expression of TGF-beta1 by downregulating of pERK1/2, p38MAPK and IkappaB phosphorylations in GMCs under diabetic condition and retard the development of diabetic complications such as diabetic nephropathy. PMID- 27002410 TI - Potent anti-angiogenic and cytotoxic effect of conferone on human colorectal adenocarcinoma HT-29 cells. AB - BACKGROUND: Cancer is one of the leading causes of death worldwide, both in developed and developing countries. Of note, colorectal adenoma encompasses a high rate of gastrointestinal-associated cancer death in human being. Today, different strategies, including surgery approaches, photodynamic therapy, radiation and particularly natural compounds have been extensively used to manage tumor behavior in human body. METHODS: The objective of the present study was to elucidate the multilateral effects of conferone on HT-29 cell lines. In addition to cell cytotoxicity, the extent of lipid peroxidation, MDA formation, catalase, superoxide dismutase and intracellular ROS levels, as markers of oxidative stress, were also studied. P-glycoprotein-mediated cellular efflux effectiveness, anti-angiogenic and finally anti-migratory capacities of conferone-exposed HT-29 cells were monitored over a course of 72 h. RESULTS: It was found that, conferone mediated cell proliferation arrest and induced cell death through both apoptosis and necrosis phenomena. HT-29 cells, exposed to 20 uM conferone, under gone oxidative stress and total content of reactive oxygen species was increased in a time-dependent manner. Intracellular accumulation of rhodamine 123 and cell's swelling under iso- and hypo-osmotic conditions could be related to P glycoprotein incorrect performance in the presence of conferone. A significant reduction in CD31 positive cells population and in vitro tubulogenesis of endothelial cells was also observed after incubation with conditioned medium collected from 72 h conferone-treated HT-29 cells. Conferone also precluded angiogenesis capability of treated HT-29 cells through an altered secretome profile, including vascular endothelial growth factor, Angiopoietin-1 and -2 factors. In addition to anti-angiogenic properties of conferone, a profound decrease in migration capability of HT-29 cells was also evident. PMID- 27002411 TI - Cleistopholine isolated from Enicosanthellum pulchrum exhibits apoptogenic properties in human ovarian cancer cells. AB - BACKGROUND: Cleistopholine is a natural alkaloid present in plants with numerous biological activities. However, cleistopholine has yet to be isolated using modern techniques and the mechanism by which this alkaloid induces apoptosis in cancer cells remains to be elucidated. HYPOTHESIS/PURPOSE: This study aims to isolate cleistopholine from the roots of Enicosanthellum pulchrum by using preparative-HPLC technique and explore the mechanism by which this alkaloid induces apoptosis in human ovarian cancer (CAOV-3) cells in vitro from 24 to 72 h. This compound may be developed as an anticancer agent that induces apoptosis in ovarian cancer cells. STUDY DESIGN/METHODS: Cytotoxicity was assessed via the cell viability assay and changes in cell morphology were observed via the acridine orange/propidium iodide (AO/PI) assay. The involvement of apoptotic pathways was evaluated through caspase analysis and multiple cytotoxicity assays. Meanwhile, early and late apoptotic events via the Annexin V-FITC and DNA laddering assays, respectively. The mechanism of apoptosis was explored at the molecular level by evaluating the expression of specific genes and proteins. In addition, the proliferation of CAOV-3-cells treated with cleistopholine was analysed using the cell cycle arrest assay. RESULTS: The IC50 of cleistopholine (61.4 uM) was comparable with that of the positive control cisplatin (62.8 uM) at 24 h of treatment. Apoptos is was evidenced by cell membrane blebbing, chromatin compression and formation of apoptotic bodies. The initial phase of apoptosis was detected at 24 h by the increase in Annexin V-FITC binding to cell membranes. A DNA ladder was formed at 48 h, indicating DNA fragmentation in the final phase of apoptosis. The mitochondria participated in the process by stimulating the intrinsic pathway via caspase 9 with a reduction in mitochondrial membrane potential (MMP) and an increase in cytochrome c release. Cell death was further validated through the mRNA and protein overexpression of Bax, caspase 3 and caspase 9 in the treated cells compared with the untreated cells. In contrast, Bcl-2, Hsp70 and survivin decreased in expression upon cleistopholine treatment. Cell cycle was arrested at the G0/G1 phase and cell population percentage significantly increased to 43.5%, 45.4% and 54.3% in time-dependent manner in the cleistopholine-treated CAOV-3 cells compared with the untreated cells at 24, 48 and 72 h respectively. CONCLUSION: The current study indicated that cleistopholine can be a potential candidate as a new drug to treat ovarian cancer disease. PMID- 27002413 TI - Evaluation of the new simple and objective clinical decision rule "I-DVT" in patients with clinically suspected acute deep vein thrombosis. AB - INTRODUCTION: The Wells rule is the recommended first step in the work-up of suspected deep vein thrombosis (DVT). However, it is often incorrectly used leading to an excessive number of diagnostic tests used in daily practice and diagnostic failures. A simpler objective risk stratification tool may improve adherence to the guidelines. We evaluated the diagnostic performance of the I-DVT score, which consists of four easy assessable variables: Immobilization, >3cm Difference in calve circumferences, prior Venous thromboembolism (VTE) and active malignant Tumor. METHODS: We performed an observational study in 617 consecutive patients with suspected DVT. All patients were managed according to the recommended algorithm starting with the Wells rule followed by D-dimer test and/or compression ultrasonography (CUS). The I-DVT score was prospectively calculated at baseline and evaluated post-hoc. RESULTS: The DVT prevalence was 36%. DVT could be excluded in 13% of patients without CUS by the Wells rule and a normal D-dimer test, with a 3-month VTE incidence of 1.2% (95%CI 0.03-6.5%). Using the I-DVT score, DVT would have been excluded in 9.1% of patients without additional CUS, with a 3-month VTE incidence of 0% (95%CI 0.0-6.4%). The area under the ROC curve (AUC) was 0.70 (95%CI 0.66-0.74) and 0.65 (95%CI 0.61-0.70) for the Wells rule and I-DVT score respectively (difference 0.049, 95%CI -0.01 0.11; p=0.13). CONCLUSIONS: The simple I-DVT score and Wells rule have comparable diagnostic accuracy. It's safety, efficiency and associated potential improvement of guideline adherence in clinical practice has to be further evaluated in a prospective management study. PMID- 27002412 TI - NF-kappaB pathway inhibition by anthrocyclic glycoside aloin is key event in preventing osteoclastogenesis in RAW264.7 cells. AB - BACKGROUND: Osteoporosis is a bone pathology leading to increased fracture risk and challenging the quality of life. As current treatments can exhibit deleterious side effects, the use of phyto-compounds with therapeutic and preventive activities against orthopaedic related problems represents a promising alternative. PURPOSE: We investigated the effect of aloin, an anthrocyclic compound, on inhibition of osteoclastogenesis using receptor of the nuclear factor kappaB (NF-kappaB) ligand (RANKL)-induced RAW264.7 macrophage cells. STUDY DESIGN/METHODS: The inhibitory effect of aloin on in vitro osteoclastogenesis was evaluated by reduction in tartrate-resistant acid phosphatase (TRAP) content and expression levels of osteoclast-specific gene, cathepsin K. Multinuclear formation of osteoclast was assessed with haematoxylin and eosin staining. F4/80 content the marker of the murine monocyte/macrophage cells, was evaluated by immunocytochemistry. The underlining mechanisms were assessed by Western blots and EMSA. Effect of aloin on generation of intracellular reactive oxygen species (ROS) was estimated by dichlorofluorescein diacetate (DCFH-DA). Bone degradation effect was evaluated by bone pit assay. The bone pit culture supernatant was studied by Fluorescein assay. RESULTS: We demonstrated that aloin reduced TRAP content and levels of osteoclast-specific gene and protein, cathepsin K. Treatment with aloin (0.75 uM) prevented multinuclear formation (haematoxylin and eosin staining), reduced intracellular TRAP content (TRAP Staining) and increased F4/80 content (F4/80 immunohistochemistry) in RANKL (20 ng/ml) treated RAW cells. Treatment of the RAW cells with aloin suppressed RANKL-induced NF-kappaB pathway components like IKKalpha, IKKbeta, Phospho.IKK alpha/beta, NF-kappaB-p65, Phospho NF-kappaB-p65 and IkappaBalpha. EMSA studies showed aloin dose dependently reduced DNA binding activity of NF-kappaB. Additionally, in vitro bone pit assay revealed that aloin prevented bone degradation and also decreased the fluorescence content in cells, thus confirming the role of aloin in inhibition of osteoclastogenesis . CONCLUSION: Collectively, this study identifies aloin as a potent inhibitor of osteoclastogenesis and bone resorption. The action of aloin was in par with alendronate sodium trihydrate and may provide evidence for its therapeutic potential to treat diseases involving abnormal bone lysis. PMID- 27002415 TI - Serum Vitamin D Levels in Patients with Acute Anterior Uveitis. AB - PURPOSE: To evaluate serum 25-hydroxyvitamin D levels in patients with acute anterior uveitis (AAU). METHODS: This observational case-control study involved 20 patients with AAU, and 20 consecutive, age and sex-matched healthy subjects without any ocular or systemic diseases. Serum 25-hydroxyvitamin D was quantified with electrochemiluminescence technique. RESULTS: No significant differences were found between the groups with respect to age (p = 0.185) and sex (p = 0.465). Serum vitamin D levels of the subjects with AAU (mean 5.75 +/- 4.50 ng/mL, median 4.00 ng/mL, range: 3.00-19.00 ng/mL) were significantly lower than the control group (mean 12.96 +/- 5.89 ng/mL, median 11.00 ng/mL, range: 5.20-25.92 ng/mL) (p<0.001). CONCLUSIONS: We found significantly low serum levels of vitamin D in patients with AAU, which suggest that vitamin D deficiency may play a role in the pathogenesis of anterior uveitis. Further studies are necessary to demonstrate the efficacy of vitamin D supplementation in the management of patients with anterior uveitis. PMID- 27002414 TI - BMPR2 mutation is a potential predisposing genetic risk factor for congenital heart disease associated pulmonary vascular disease. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) frequently arises in patients with congenital heart disease (CHD) and can lead to pulmonary vascular disease (PVD). The present study was initiated to distinguish the predisposing effect of bone morphogenetic protein receptor 2 (BMPR2) in CHD by comparing the different mutation features of BMPR2 between CHD patients with or without PVD. METHODS AND RESULTS: 294 CHD-PVD and 161 CHD without PVD patients were enrolled. PAH was diagnosed by heart catheterization at rest after CHD was first recognized by echocardiography. PVD was defined as a pulmonary vascular resistance (PVR) more than 3 Wood units. BMPR2 gene was screened by direct sequencing. A total of 24 mutations were identified, accounting for 22 of the 294 patients with CHD-PVD (7.5%) and 2 of the 161 CHD patients without PVD (1.2%, P=0.004). Female/male CHD PVD patient ratio was 1.6:1, while in the BMPR2 mutation carriers female patients were more dominant (4.5:1, P=0.042). A significant higher BMPR2 mutation rate (12.6%) was found in repaired CHD-PVD (P=0.010). BMPR2 mutations in CHD-PVD patients were identified in different clinical phenotypes. Missense mutation of BMPR2 is the dominant mutation type. CONCLUSION: Genetic predisposing factor may be an important component in the process of development of PVD in CHD patients. Female, repaired patients are more likely to be detected with genetic mutations. PMID- 27002416 TI - Linguistic analysis of discourse in aphasia: A review of the literature. AB - This review examined previous research applications of linguistic discourse analysis to assess the language of adults with aphasia. A comprehensive literature search of seven databases identified 165 studies that applied linguistic measures to samples of discourse collected from people with aphasia. Analysis of methodological applications revealed an increase in published research using linguistic discourse analysis over the past 40 years, particularly to measure the generalisation of therapy outcomes to language in use. Narrative language samples were most frequently subject to analysis though all language genres were observed across included studies. A total of 536 different linguistic measures were applied to examine language behaviours. Growth in the research use of linguistic discourse analysis and suggestions that this growth may be reflected in clinical practice requires further investigation. Future research directions are discussed to investigate clinical use of discourse analysis and examine the differences that exist between research and clinical practice. PMID- 27002417 TI - Regulation of poly(A) RNA retention in the nucleus as a survival strategy of plants during hypoxia. AB - Last finding indicates that post-transcriptional processes are significant in low oxygen conditions, but their nature is poorly understood. Here, we localized poly(A) RNA and mRNA coding proteins involved and not involved with resistance to hypoxia in Lupinus luteus and Arabidopsis thaliana during submergence and after recovery of aerobic conditions. We showed a strong nuclear accumulation of poly(A) RNA and 6 of 7 studied mRNAs with a concurrent strong reduction in RNA polymerase II transcription during hypoxia. In this study, the nucleus did not accumulate mRNA of the ADH1 (alcohol dehydrogenase 1) gene, which is a core hypoxia gene. The RNA accumulation in the nucleus is among the mechanisms of post transcriptional gene regulation that prevents translation. However re-aeration was accompanied by a strong increase in the amount of the mRNAs in the cytoplasm and a simultaneous decrease in nuclear mRNAs. This finding indicates that the nucleus is a storage site for those of mRNAs which are not involved in the response to hypoxia for use by the plants after the hypoxic stress. In this study, the highest intensity of RNA accumulation occurred in Cajal bodies (CBs); the intensity of accumulation was inversely correlated with transcription. Under hypoxia, ncb-1 mutants of Arabidopsis thaliana with a complete absence of CBs died sooner than wild type (WT), accompanied by a strong reduction in the level of poly(A) RNA in the nucleus. These results suggest that the CBs not only participate in the storage of the nuclear RNA, but they also could take part in its stabilization under low-oxygen conditions. PMID- 27002418 TI - The Impact of Acquisition Dose on Quantitative Breast Density Estimation with Digital Mammography: Results from ACRIN PA 4006. AB - Purpose To investigate the impact of radiation dose on breast density estimation in digital mammography. Materials and Methods With institutional review board approval and Health Insurance Portability and Accountability Act compliance under waiver of consent, a cohort of women from the American College of Radiology Imaging Network Pennsylvania 4006 trial was retrospectively analyzed. All patients underwent breast screening with a combination of dose protocols, including standard full-field digital mammography, low-dose digital mammography, and digital breast tomosynthesis. A total of 5832 images from 486 women were analyzed with previously validated, fully automated software for quantitative estimation of density. Clinical Breast Imaging Reporting and Data System (BI RADS) density assessment results were also available from the trial reports. The influence of image acquisition radiation dose on quantitative breast density estimation was investigated with analysis of variance and linear regression. Pairwise comparisons of density estimations at different dose levels were performed with Student t test. Agreement of estimation was evaluated with quartile-weighted Cohen kappa values and Bland-Altman limits of agreement. Results Radiation dose of image acquisition did not significantly affect quantitative density measurements (analysis of variance, P = .37 to P = .75), with percent density demonstrating a high overall correlation between protocols (r = 0.88-0.95; weighted kappa = 0.83-0.90). However, differences in breast percent density (1.04% and 3.84%, P < .05) were observed within high BI-RADS density categories, although they were significantly correlated across the different acquisition dose levels (r = 0.76-0.92, P < .05). Conclusion Precision and reproducibility of automated breast density measurements with digital mammography are not substantially affected by variations in radiation dose; thus, the use of low-dose techniques for the purpose of density estimation may be feasible. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 27002419 TI - Subjective Cognitive Decline: Mapping Functional and Structural Brain Changes-A Combined Resting-State Functional and Structural MR Imaging Study. AB - Purpose To determine whether individuals with subjective cognitive decline (SCD) exhibit functional and structural brain alterations by using resting-state functional and structural magnetic resonance (MR) imaging. Materials and Methods This study received institutional review board approval, and all participants gave informed consent. Resting-state functional MR imaging and structural MR imaging techniques were used to measure amplitude of low-frequency fluctuations (ALFF) and regional gray matter volume in 25 subjects with SCD (mean age, 65.52 years +/- 6.12) and 61 control subjects (mean age, 64.11 years +/- 8.59). Voxel wise general linear model analyses were used to examine between-group differences in ALFF or in gray matter volume and to further determine the brain-behavioral relationship. Results Subjects with SCD exhibited higher ALFF values than did control subjects in the bilateral inferior parietal lobule (left: 0.44 +/- 0.25 vs 0.27 +/- 0.18, respectively; P = .0003; right: 1.46 +/- 0.45 vs 1.10 +/- 0.37, respectively; P = .0015), right inferior (0.45 +/- 0.15 vs 0.37 +/- 0.08, repectively; P = .0106) and middle (1.03 +/- 0.32 vs 0.83 +/- 0.20, respectively; P = .0008) occipital gyrus, right superior temporal gyrus (0.11 +/- 0.07 vs 0.07 +/- 0.04, respectively; P = .0016), and right cerebellum posterior lobe (0.51 +/- 0.27 vs 0.39 +/- 0.15, respectively; P = .0010). In the SCD group, significant correlations were found between Auditory Verbal Learning Test recognition scores and ALFF in the left inferior parietal lobe (r = -0.79, P < .001) and between Auditory Verbal Learning Test immediate recall scores and ALFF values in the right middle occipital gyrus (r = -0.64, P = .002). Nonsignificant group differences were found in gray matter volume (P > .05, corrected). Conclusion Individuals with SCD had altered spontaneous functional activity, suggesting that resting-state functional MR imaging may be a noninvasive method for characterizing SCD. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 27002420 TI - Correlates of Executive Functions in Multiple Sclerosis Based on Structural and Functional MR Imaging: Insights from a Multicenter Study. AB - Purpose To study the concomitant use of structural and functional magnetic resonance (MR) imaging correlates to explain information processing speed (IPS) and executive function (EF) in multiple sclerosis (MS). Materials and Methods Local ethics committee approval was obtained at all sites for this prospective, multicenter study. All subjects provided written informed consent. Twenty-six patients with relapsing-remitting MS and 32 healthy control subjects from four centers underwent structural and functional MR imaging, including a go/no-go task and neuropsychological assessment. Subtests of the Brief Repeatable Battery of Neuropsychological Tests, the Wisconsin Card Sorting Test, and the performance with the functional MR imaging paradigm were used as estimates of IPS and EF. Activation of the thalamus and the inferior frontal gyrus (pars triangularis), thalamic volume, T2 lesion load, and age were used to explain IPS and EF in regression models. Results Compared with control subjects, patients showed increased activation in a frontoparietal network, including both thalami, during the execution of the go/no-go task. Patients had decreased thalamic volume (P < .001). Among tested variables, thalamic volume (beta = 0.606, P = .001), together with thalamic activation (beta = -0.410, P = .022), were the best predictors of IPS and EF and helped explain 52.7% of the variance in IPS and EF. Conclusion This study highlights the potential of the combined use of functional and morphologic parameters to explain IPS and EF in patients with relapsing-remitting MS and confirms the central role of the thalamus as a relay station in executive functioning. ((c)) RSNA, 2016. PMID- 27002421 TI - Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks. AB - OBJECTIVES: Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been associated with weight loss in a broad range of patients with type 2 diabetes mellitus (T2DM). This analysis further evaluated changes in body weight and composition with canagliflozin in two 104-week, Phase 3 studies. METHODS: In Study 1, patients aged 18-80 years (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride as add-on to metformin for a 52-week core treatment period, followed by a 52-week extension period. In Study 2, patients aged 55-80 years (N = 714) received canagliflozin 100 or 300 mg or placebo added to stable background antihyperglycemic agents for a 26-week core treatment period, followed by a 78 week extension period. Percent change from baseline in body weight; proportion of patients with any weight loss, >=5% weight loss, and >=10% weight loss; change in body mass index (BMI) and waist circumference; change in body weight across weight-loss quartiles; and changes in body composition were evaluated in both studies. RESULTS: Canagliflozin 100 and 300 mg provided sustained weight loss versus either glimepiride or placebo over 104 weeks. More patients experienced any weight loss and >=5% weight loss with canagliflozin versus comparator. Across the 3 highest weight-loss quartiles, canagliflozin provided greater weight loss versus glimepiride or placebo. BMI and waist circumference reductions were observed with canagliflozin 100 and 300 mg versus either glimepiride or placebo over 104 weeks; more patients had BMI or waist circumference reductions with canagliflozin versus comparator. Body composition analysis indicated that the majority of weight loss was due to loss of fat mass. Canagliflozin was generally well tolerated, with increased incidence of adverse events related to the SGLT2 inhibition mechanism. CONCLUSIONS: Canagliflozin 100 and 300 mg provided sustained reductions in body weight, BMI, and waist circumference in a greater proportion of patients with T2DM versus glimepiride or placebo over 104 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT00968812, NCT01106651. PMID- 27002424 TI - Do women with recurrent miscarriage constitute a high-risk obstetric population? AB - The aim of this study was to examine if women with history of recurrent miscarriage have a higher risk of maternal and foetal complications in future pregnancies. This was a retrospective case control study that analysed data collected prospectively between 2001 and 2007 from 400 women with history of recurrent miscarriage who achieved pregnancies progressing beyond 24 weeks gestation compared to 39,860 deliveries from the general obstetric database within the same time period. Results showed that women with recurrent miscarriage had significantly increased odds of low Apgar scores at one (odds ratios (OR) 1.57, 95% CI 1.20-2.05) and five minutes (OR 2.0, 95% CI 1.23-3.27), small for gestational age (OR 1.96, 95% CI 1.12-3.43), preterm delivery (OR 1.64, 95% CI 1.22-2.19) and antepartum haemorrhage (OR 7.67, 95% CI 4.23-13.91). The risks were increased in the presence of a male foetus but no difference was observed between primary and secondary miscarriage patients. In conclusion, women with recurrent miscarriage have an increased risk of several maternal and foetal complications and therefore may require closer monitoring during the antenatal period particularly when pregnant with a male foetus. PMID- 27002423 TI - Investigation of association between hip morphology and prevalence of osteoarthritis. AB - The cause of hip osteoarthritis (OA) remains unclear, morphologic abnormality of hip was thought to be a contributing factor to hip OA. The hypothesis was that there were subtle anatomical morphology differences of the hip between normal and OA subjects; the objective of this study was to explore these anatomical differences which are predisposing to hip OA based on CT 3D reconstruction. Ninety-three normal subjects (186 hips) and 66 mild-to-moderate hip OA subjects (132 hips) were recruited in this study. Three parameters of the head-neck relationship were assessed: translation, rotation and concavity. Translation was the potential translational movements of femoral head related to the neck's axis. Rotation was described by the physeal scar to evaluate the rotation tendency of femoral head related to the neck at the head-neck junction. Concavity was used to assess the sphericity of the head as it joins the neck. The femoral neck anteversion angle and some parameters of the acetabulum: anteversion, inclination and CE angle were measured too. By comparison, it was found that OA subjects had less femoral head sphericity, head-neck junction concavity, acetabular and femoral neck anteversion angle; but greater acetabular coverage. These characteristics increased the risk of hip OA in OA subjects. PMID- 27002425 TI - A 50 bp deletion in the SOD1 promoter lowers enzyme expression but is not associated with ALS in Sweden. AB - Mutations in the superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). A 50 base pair (bp) deletion of SOD1 has been suggested to reduce transcription and to be associated with later disease onset in ALS. This study was aimed to reveal if the 50 bp deletion influenced SOD1 enzymatic activity, occurrence and phenotype of the disease in a Swedish ALS/control cohort. Blood samples from 512 Swedish ALS patients and 354 Swedish controls without coding SOD1 mutations were analysed for the 50 bp deletion allele. The enzymatic activity of SOD1 in erythrocytes was analysed and genotype-phenotype correlations were assessed. Results demonstrated that the genotype frequencies of the 50 bp deletion were all found to be in Hardy-Weinberg equilibrium. No significant differences were found for age of onset, disease duration or site of onset. SOD1 enzymatic activity showed a statistically significant decreasing trend in the control group, in which the allele was associated with a 5% reduction in SOD1 activity. The results suggest that the 50 bp deletion has a moderate reducing effect on SOD1 synthesis. No modulating effects, however, were found on ALS onset, phenotype and survival in the Swedish population. PMID- 27002428 TI - Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature. AB - OBJECTIVE: Rubella virus infection during the first trimester of pregnancy can cause congenital rubella syndrome (CRS). We aimed to describe the abnormalities in order to define the ultrasound features to look for when performing prenatal scans. The goal of this review is to focus specifically on the signs of CRS accessible to prenatal diagnosis. METHODS: We analyzed every case of CRS described before and/or after birth that we identified in the Pubmed database and classified them as accessible or not to prenatal diagnosis. RESULTS: The most frequently reported malformations accessible to prenatal diagnosis were: cardiac septal defects, pulmonary artery stenosis, microcephaly, cataract, microphtalmia, and hepatosplenomegaly. CONCLUSION: This extensive literature review shows that the ultrasound features of CRS are not well known, even though rubella was the first teratogenic virus described. This review will help clinicians in the management of rubella during pregnancy by clarifying the findings to be sought. PMID- 27002432 TI - Evening: Kenneth M. Adams. PMID- 27002429 TI - A hormone-related female anti-aphrodisiac signals temporary infertility and causes sexual abstinence to synchronize parental care. AB - The high energetic demand of parental care requires parents to direct their resources towards the support of existing offspring rather than investing into the production of additional young. However, how such a resource flow is channelled appropriately is poorly understood. In this study, we provide the first comprehensive analysis of the physiological mechanisms coordinating parental and mating effort in an insect exhibiting biparental care. We show a hormone-mediated infertility in female burying beetles during the time the current offspring is needy and report that this temporary infertility is communicated via a pheromone to the male partner, where it inhibits copulation. A shared pathway of hormone and pheromone system ensures the reliability of the anti-aphrodisiac. Female infertility and male sexual abstinence provide for the concerted investment of parental resources into the existing developing young. Our study thus contributes to our deeper understanding of the mechanisms underlying adaptive parental decisions. PMID- 27002441 TI - Equity in Cancer Care and Outcomes of Treatment: A Different Type of Cancer Moonshot. PMID- 27002442 TI - A PIECE OF MY MIND. The Power of "My". PMID- 27002443 TI - Is It Time to Make Mind-Body Approaches Available for Chronic Low Back Pain? PMID- 27002444 TI - Data Sharing: An Ethical and Scientific Imperative. PMID- 27002445 TI - Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial. AB - IMPORTANCE: Mindfulness-based stress reduction (MBSR) has not been rigorously evaluated for young and middle-aged adults with chronic low back pain. OBJECTIVE: To evaluate the effectiveness for chronic low back pain of MBSR vs cognitive behavioral therapy (CBT) or usual care. DESIGN, SETTING, AND PARTICIPANTS: Randomized, interviewer-blind, clinical trial in an integrated health care system in Washington State of 342 adults aged 20 to 70 years with chronic low back pain enrolled between September 2012 and April 2014 and randomly assigned to receive MBSR (n = 116), CBT (n = 113), or usual care (n = 113). INTERVENTIONS: CBT (training to change pain-related thoughts and behaviors) and MBSR (training in mindfulness meditation and yoga) were delivered in 8 weekly 2-hour groups. Usual care included whatever care participants received. MAIN OUTCOMES AND MEASURES: Coprimary outcomes were the percentages of participants with clinically meaningful (>=30%) improvement from baseline in functional limitations (modified Roland Disability Questionnaire [RDQ]; range, 0-23) and in self-reported back pain bothersomeness (scale, 0-10) at 26 weeks. Outcomes were also assessed at 4, 8, and 52 weeks. RESULTS: There were 342 randomized participants, the mean (SD) [range] age was 49.3 (12.3) [20-70] years, 224 (65.7%) were women, mean duration of back pain was 7.3 years (range, 3 months-50 years), 123 (53.7%) attended 6 or more of the 8 sessions, 294 (86.0%) completed the study at 26 weeks, and 290 (84.8%) completed the study at 52 weeks. In intent-to-treat analyses at 26 weeks, the percentage of participants with clinically meaningful improvement on the RDQ was higher for those who received MBSR (60.5%) and CBT (57.7%) than for usual care (44.1%) (overall P = .04; relative risk [RR] for MBSR vs usual care, 1.37 [95% CI, 1.06-1.77]; RR for MBSR vs CBT, 0.95 [95% CI, 0.77-1.18]; and RR for CBT vs usual care, 1.31 [95% CI, 1.01-1.69]). The percentage of participants with clinically meaningful improvement in pain bothersomeness at 26 weeks was 43.6% in the MBSR group and 44.9% in the CBT group, vs 26.6% in the usual care group (overall P = .01; RR for MBSR vs usual care, 1.64 [95% CI, 1.15-2.34]; RR for MBSR vs CBT, 1.03 [95% CI, 0.78-1.36]; and RR for CBT vs usual care, 1.69 [95% CI, 1.18-2.41]). Findings for MBSR persisted with little change at 52 weeks for both primary outcomes. CONCLUSIONS AND RELEVANCE: Among adults with chronic low back pain, treatment with MBSR or CBT, compared with usual care, resulted in greater improvement in back pain and functional limitations at 26 weeks, with no significant differences in outcomes between MBSR and CBT. These findings suggest that MBSR may be an effective treatment option for patients with chronic low back pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01467843. PMID- 27002446 TI - Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution: A Randomized Clinical Trial. AB - IMPORTANCE: Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. OBJECTIVE: To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. DESIGN, SETTING, AND PARTICIPANTS: Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. INTERVENTIONS: Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. MAIN OUTCOMES AND MEASURES: Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of -15%. RESULTS: There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, -3.0% to infinity; P < .001). Given the prespecified noninferiority margin of -15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01221311. PMID- 27002447 TI - Antibiotic Exposure During the First 6 Months of Life and Weight Gain During Childhood. AB - IMPORTANCE: Early-life antibiotic exposure has been associated with increased adiposity in animal models, mediated through the gut microbiome. Infant antibiotic exposure is common and often inappropriate. Studies of the association between infant antibiotics and childhood weight gain have reported inconsistent results. OBJECTIVE: To assess the association between early-life antibiotic exposure and childhood weight gain. DESIGN AND SETTING: Retrospective, longitudinal study of singleton births and matched longitudinal study of twin pairs conducted in a network of 30 pediatric primary care practices serving more than 200,000 children of diverse racial and socioeconomic backgrounds across Pennsylvania, New Jersey, and Delaware. PARTICIPANTS: Children born between November 1, 2001, and December 31, 2011, at 35 weeks' gestational age or older, with birth weight of 2000 g or more and in the fifth percentile or higher for gestational age, and who had a preventive health visit within 14 days of life and at least 2 additional visits in the first year of life. Children with complex chronic conditions and those who received long-term antibiotics or multiple systemic corticosteroid prescriptions were excluded. We included 38,522 singleton children and 92 twins (46 matched pairs) discordant in antibiotic exposure. Final date of follow-up was December 31, 2012. EXPOSURE: Systemic antibiotic use in the first 6 months of life. MAIN OUTCOMES AND MEASURES: Weight, measured at preventive health visits from age 6 months through 7 years. RESULTS: Of 38,522 singleton children (50% female; mean birth weight, 3.4 kg), 5287 (14%) were exposed to antibiotics during the first 6 months of life (at a mean age of 4.3 months). Antibiotic exposure was not significantly associated with rate of weight change (0.7%; 95% CI, -0.1% to 1.5%; P = .07, equivalent to approximately 0.05 kg; 95% CI, -0.004 to 0.11 kg of added weight gain between age 2 years and 5 years). Among 92 twins (38% female; mean birth weight, 2.8 kg), the 46 twins who were exposed to antibiotics during the first 6 months of life received them at a mean age of 4.5 months. Antibiotic exposure was not significantly associated with a weight difference (-0.09 kg; 95% CI, -0.26 to 0.08 kg; P = .30). CONCLUSIONS AND RELEVANCE: Exposure to antibiotics within the first 6 months of life compared with no exposure was not associated with a statistically significant difference in weight gain through age 7 years. There are many reasons to limit antibiotic exposure in young, healthy children, but weight gain is likely not one of them. PMID- 27002449 TI - Bariatric Surgery for Type 2 Diabetes: Getting Closer to the Long-term Goal. PMID- 27002450 TI - Screening for Gonorrhea, Chlamydia, and Hepatitis B. PMID- 27002448 TI - Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial. AB - IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. OBJECTIVE: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah. INTERVENTIONS: Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months. MAIN OUTCOMES AND MEASURES: The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden. RESULTS: Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. [table: see text]. CONCLUSIONS AND RELEVANCE: Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT 01187901. PMID- 27002451 TI - ERBB2 (HER2) Testing in Breast Cancer. PMID- 27002452 TI - Use of Open Access Platforms for Clinical Trial Data. PMID- 27002453 TI - Intensive Care Unit Admission and Mortality Among Medicare Beneficiaries With Pneumonia. PMID- 27002454 TI - Repeat Tdap Vaccination and Adverse Birth Outcomes. PMID- 27002455 TI - Intensive Care Unit Admission and Mortality Among Medicare Beneficiaries With Pneumonia--Reply. PMID- 27002456 TI - Nonlinear Exposure-Outcome Associations and Public Health Policy. PMID- 27002457 TI - Repeat Tdap Vaccination and Adverse Birth Outcomes--Reply. PMID- 27002458 TI - Nonlinear Exposure-Outcome Associations and Public Health Policy. PMID- 27002459 TI - Nonlinear Exposure-Outcome Associations and Public Health Policy--Reply. PMID- 27002461 TI - Medical Ethics: Medical Etiquette. PMID- 27002462 TI - JAMA PATIENT PAGE. Treating Constipation With Medications. PMID- 27002463 TI - Attitudes Toward Use of Benzodiazepines among U.S. Hospice Clinicians: Survey and Review of the Literature. AB - BACKGROUND: Benzodiazepines are commonly used in inpatient hospices internationally. U.S. hospice clinician views toward benzodiazepines are unknown. OBJECTIVES: Study objectives were (1) to assess inpatient hospice clinician attitudes towards the benefits of benzodiazepines for various indications and (2) to compare these attitudes to current clinical recommendations and literature. METHODS: A survey was developed and distributed to hospices with inpatient units nationwide. Results were analyzed, then compared to current clinical guidelines. Literature review was performed. U.S. hospice physicians and nurses were the study subjects. Participants were asked to indicate their level of agreement regarding benefit from benzodiazepines for various end-of-life symptoms and to answer questions regarding benzodiazepines in delirium. RESULTS: Of 143 surveys returned, 128 surveys were completed. For anxiety, 80% of participants agreed that benzodiazepines were beneficial for restlessness, dyspnea 77%, insomnia 68%, dying process 65%, agitation 57%, nausea 54%, hyperactive delirium 42%, and severe pain 38%. Nurses found benzodiazepines beneficial for more indications than physicians. Over 50% reported benzodiazepines on their order sets for agitation, insomnia, acute anxiety, chronic anxiety, chronic panic, restlessness, seizures, and withdrawal. Among physicians, 39% believe that benzodiazepines are overused within their own hospice. A literature review found very limited evidence of overall benefit from benzodiazepines for the symptoms listed above. In addition, this revealed significant evidence for risks and harms from benzodiazepines, particularly in patients at risk for delirium. CONCLUSIONS: Benzodiazepines are viewed favorably by most hospice nurses and many hospice physicians for various indications, despite little supportive clinical evidence along with significant potential for harm. PMID- 27002464 TI - Intraocular T-cell Lymphoma: Clinical Presentation, Diagnosis, Treatment, and Outcome. AB - PURPOSE: To report on the clinical data of seven patients with T-cell intraocular lymphoma (IOL). METHODS: Retrospective case series. RESULTS: Seven immunocompetent patients, 12 eyes, 6 women, with T-cell-IOL were included from five countries. Mean age was 53.5 years (range: 25-82). Four patients had systemic-ocular lymphoma, two had CNS-ocular lymphoma, and one had systemic-CNS- ocular lymphoma. Vitritis was the most frequent clinical sign, followed by anterior uveitis and serous retinal detachment. Cytopathologic examination was performed on all ocular specimens (vitreous in six and iris mass biopsy in one patient). Adjunctive diagnostic procedures included immunohistochemistry, molecular tests, and cytokine profiling of vitreous samples. Treatment modalities included systemic chemotherapy (five patients), intravitreal methotrexate (three patients), globe radiotherapy, and intrathecal chemotherapy. Mean survival from diagnosis was 21.7 months (range: 2-69). Two patients are still alive. CONCLUSIONS: T-cell IOL has variable clinical manifestations and prognosis. Systemic involvement, SRD, and vitreoretinal involvement were frequently observed. PMID- 27002466 TI - Volatile Anesthetics. Is a New Player Emerging in Critical Care Sedation? AB - Volatile anesthetic agent use in the intensive care unit, aided by technological advances, has become more accessible to critical care physicians. With increasing concern over adverse patient consequences associated with our current sedation practice, there is growing interest to find non-benzodiazepine-based alternative sedatives. Research has demonstrated that volatile-based sedation may provide superior awakening and extubation times in comparison with current intravenous sedation agents (propofol and benzodiazepines). Volatile agents may possess important end-organ protective properties mediated via cytoprotective and antiinflammatory mechanisms. However, like all sedatives, volatile agents are capable of deeply sedating patients, which can have respiratory depressant effects and reduce patient mobility. This review seeks to critically appraise current volatile use in critical care medicine including current research, technical consideration of their use, contraindications, areas of controversy, and proposed future research topics. PMID- 27002465 TI - Cellular Interferon Gamma and Granzyme B Responses to Cytomegalovirus-pp65 and Influenza N1 Are Positively Associated in Elderly. AB - Morbidity and mortality in the elderly are associated with viral infections, including influenza and cytomegalovirus (CMV). With increasing age, cellular immunity gains importance in protection to influenza, but latent CMV is highly prevalent and associated with immune dysfunction. An insight into the association between immunity against influenza and CMV adds to the understanding of healthy aging. Here we first aimed to measure influenza-specific cellular immunity using granzyme B (GrzB) and interferon-gamma (IFN-gamma)-ELISpot. Next, influenza specific cellular immunity was associated with humoral and cellular CMV-specific immunity in healthy 65+ elderly. Vaccine trial participants gave additional blood samples 3 weeks after receiving a H1N1 containing vaccine. CMV serology was determined and peripheral blood mononuclear cells were stimulated with influenza N1 or CMV pp65-derived peptide pools for 7 days and rechallenged to assess antigen-specific GgrzB and IFN-gamma responses using ELISpot assays. Results were compared using chi-square and correlation analysis. Eighty-three individuals (60% men, 65% CMV IgG+, age range 65-78y) participated. We found significant positive associations between IFN-gamma and GrzB responses to both influenza and CMV, but also between a positive CMV serostatus and an influenza N1-specific activation marker response (p = 0.013). CMV pp65 responses were detected in CMV IgG+ individuals, but remarkably also in CMV IgG- individuals (27%). In this study, following influenza vaccination, elderly with cellular immunity against CMV were more likely to have cellular immunity against influenza vaccine N1 antigen. These findings stress the need to continue exploring the possible role of CMV in immunosenescence. PMID- 27002470 TI - Clinical commissioning of an in vivo range verification system for prostate cancer treatment with anterior and anterior oblique proton beams. AB - The purpose of this work is the clinical commissioning of a recently developed in vivo range verification system (IRVS) for treatment of prostate cancer by anterior and anterior oblique proton beams. The IRVS is designed to perform a complete workflow for pre-treatment range verification and adjustment. It contains specifically designed dosimetry and electronic hardware and a specific software for workflow control with database connection to the treatment and imaging systems. An essential part of the IRVS system is an array of Si-diode detectors, designed to be mounted to the endorectal water balloon routinely used for prostate immobilization. The diodes can measure dose rate as function of time from which the water equivalent path length (WEPL) and the dose received are extracted. The former is used for pre-treatment beam range verification and correction, if necessary, while the latter is to monitor the dose delivered to patient rectum during the treatment and serves as an additional verification. The entire IRVS workflow was tested for anterior and 30 degree inclined proton beam in both solid water and anthropomorphic pelvic phantoms, with the measured WEPL and rectal doses compared to the treatment plan. Gafchromic films were also used for measurement of the rectal dose and compared to IRVS results. The WEPL measurement accuracy was in the order of 1 mm and after beam range correction, the dose received by the rectal wall were 1.6% and 0.4% from treatment planning, respectively, for the anterior and anterior oblique field. We believe the implementation of IRVS would make the treatment of prostate with anterior proton beams more accurate and reliable. PMID- 27002471 TI - Commentary on a Rethink on Hyaluronidase Injection, Intra-arterial Injection and Blindness. PMID- 27002472 TI - Basal Cell Carcinoma of the Dorsal Hand: An Update and Comprehensive Review of the Literature. AB - BACKGROUND: Excessive ultraviolet radiation (UVR) exposure is the primary predisposing factor for basal cell carcinoma (BCC). However, surprisingly, BCCs occur very rarely on the dorsal hand, which is subject to intense sun exposure, and their infrequent presentation in this location suggests that other factors besides UVR may play a role in BCC pathogenesis. Because dorsal hand BCCs are uncommon, knowledge of their characteristics is limited, and more data are needed to describe their clinical presentation and treatment. OBJECTIVE: To perform an updated review of the literature on the management of dorsal hand BCCs. METHODS: The authors conducted a comprehensive literature review by searching the PubMed database with the key phrases "basal cell carcinoma dorsal hand," "basal cell carcinoma hand," and "basal cell carcinoma finger," and "basal cell carcinoma thumb." RESULTS: The authors identified 176 cases of dorsal hand BCCs in the literature, 120 of which had sufficient data for analysis. Only 4 cases were treated with Mohs micrographic surgery (MMS). The authors present 14 additional cases of dorsal hand BCCs treated with MMS. CONCLUSION: Basal cell carcinomas on the dorsal hand occur infrequently, and potential risk factors include being a male of white descent and personal history of skin cancer. Mohs micrographic surgery seems to be an effective treatment method. PMID- 27002473 TI - Engaging older adults in the visualization of sensor data facilitated by an open platform for connected devices. AB - BACKGROUND: The use of smart home sensor systems is growing primarily due to the appeal of unobtrusively monitoring older adult health and wellness. However, integrating large-scale sensor systems within residential settings can be challenging when deployment takes place across multiple environments, requiring customization of applications, connection across various devices and effective visualization of complex longitudinal data. OBJECTIVE: The objective of the study was to demonstrate the implementation of a smart home system using an open, extensible platform in a real-world setting and develop an application to visualize data real time. METHODS: We deployed the open source Lab of Things platform in a house of 11 residents as a demonstration of feasibility over the course of 3 months. The system consisted of Aeon Labs Z-wave Door/Window sensors and an Aeon Labs Multi-sensor that collected data on motion, temperature, luminosity, and humidity. We applied a Rapid Iterative Testing and Evaluation approach towards designing a visualization interface engaging gerontological experts. We then conducted a survey with 19 older adult and caregiver stakeholders to inform further design revisions. RESULTS: Our initial visualization mockups consisted of a bar chart representing activity level over time. Family members felt comfortable using the application. Older adults however, indicated it would be difficult to learn to use the application, and had trouble identifying utility. A key for older adults was ensuring that the data collected could be utilized by their family members, physicians, or caregivers. CONCLUSIONS: The approach described in this work is generalizable towards future smart home deployments and can be a valuable guide for researchers to scale a study across multiple homes and connected devices, and to create personalized interfaces for end users. PMID- 27002474 TI - A short-stem hip implant with metaphyseal anchorage in patients with developmental dysplasia of the hip. AB - BACKGROUND: Short-stem implants are routinely used for total hip arthroplasty in younger patients that are more likely to have secondary osteoarthritis than older patients. OBJECTIVE: To investigate the applicability of short-stem hip implants for secondary osteoarthritis due to developmental dysplasia of the hip. METHODS: This study analyzed the clinical and radiological results of patients with developmental dysplasia of the hip (DDH, 58 hips) and compared them to those of patients with primary osteoarthritis (POA, 59 hips) treated with the metaphyseal total hip arthroplasty (Metha(r)) short stem with metaphyseal fixation. RESULTS: The mean clinical and radiological follow-up periods were 2.9 +/- 1.1 years and 3.8 +/- 1.9 years, respectively. The mean Harris Hip Score (HHS) significantly increased in both groups over this period (p< 0.0001). The caput-collum-diaphysis (CCD) angle was significantly lower in the POA group prior to surgery and significantly increased in the POA and and decreased in DDH groups, respectively. The preoperative femoral offset was lower in the DDH group and increased significantly after surgery. CONCLUSIONS: The Metha(r) short stem in patients with DDH allows good reconstruction of joint biomechanics with a good clinical outcome. PMID- 27002475 TI - New Alkaloids and alpha-Glucosidase Inhibitory Flavonoids from Ficus hispida. AB - Two new pyrrolidine alkaloids, ficushispimines A (1) and B (2), a new omega (dimethylamino)caprophenone alkaloid, ficushispimine C (3), and a new indolizidine alkaloid, ficushispidine (4), together with the known alkaloid 5 and 11 known isoprenylated flavonoids 6 - 16, were isolated from the twigs of Ficus hispida. Their structures were elucidated by spectroscopic methods. Isoderrone (8), 3'-(3-methylbut-2-en-1-yl)biochanin A (11), myrsininone A (12), ficusin A (13), and 4',5,7-trihydroxy-6-[(1R*,6R*)-3-methyl-6-(1-methylethenyl)cyclohex-2 en-1-yl]isoflavone (14) showed inhibitory effects on alpha-glucosidase in vitro. PMID- 27002476 TI - Isolation and identification of biocellulose-producing bacterial strains from Malaysian acidic fruits. AB - Biocellulose (BC) is pure extracellular cellulose produced by several species of micro-organisms that has numerous applications in the food, biomedical and paper industries. However, the existing biocellulose-producing bacterial strain with high yield was limited. The aim of this study was to isolate and identify the potential biocellulose-producing bacterial isolates from Malaysian acidic fruits. One hundred and ninety-three bacterial isolates were obtained from 19 local acidic fruits collected in Malaysia and screened for their ability to produce BC. A total of 15 potential bacterial isolates were then cultured in standard Hestrin Schramm (HS) medium statically at 30 degrees C for 2 weeks to determine the BC production. The most potent bacterial isolates were identified using 16S rRNA gene sequence analysis, morphological and biochemical characteristics. Three new and potent biocellulose-producing bacterial strains were isolated from soursop fruit and identified as Stenotrophomonas maltophilia WAUPM42, Pantoea vagans WAUPM45 and Beijerinckia fluminensis WAUPM53. Stenotrophomonas maltophilia WAUPM42 was the most potent biocellulose-producing bacterial strain that produced the highest amount of BC 0.58 g l(-1) in standard HS medium. Whereas, the isolates P. vagans WAUPM45 and B. fluminensis WAUPM53 showed 0.50 and 0.52 g l( 1) of BC production, respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: Biocellulose (BC) is pure extracellular cellulose that is formed by many micro organisms in the presence of carbon source and acidic condition. It can replace plant-based cellulose in multifarious applications due to its unique characteristics. In this study, three potential biocellulose-producing bacterial strains were obtained from Malaysian acidic fruits and identified as Stenotrophomonas maltophilia WAUPM42, Pantoea vagans WAUPM45 and Beijerinckia fluminensis WAUPM53. This study reports for the first time the new biocellulose producing bacterial strains isolated from Malaysian acidic fruits. PMID- 27002477 TI - Three dimensional microstructural network of elastin, collagen, and cells in Achilles tendons. AB - Similar to most biological tissues, the biomechanical, and functional characteristics of the Achilles tendon are closely related to its composition and microstructure. It is commonly reported that type I collagen is the predominant component of tendons and is mainly responsible for the tissue's function. Although elastin has been found in varying proportions in other connective tissues, previous studies report that tendons contain very small quantities of elastin. However, the morphology and the microstructural relationship among the elastic fibres, collagen, and cells in tendon tissue have not been well examined. We hypothesize the elastic fibres, as another fibrillar component in the extracellular matrix, have a unique role in mechanical function and microstructural arrangement in Achilles tendons. It has been shown that elastic fibres present a close connection with the tenocytes. The close relationship of the three components has been revealed as a distinct, integrated and complex microstructural network. Notably, a "spiral" structure within fibril bundles in Achilles tendons was observed in some samples in specialized regions. This study substantiates the hierarchical system of the spatial microstructure of tendon, including the mapping of collagen, elastin and tenocytes, with 3-dimensional confocal images. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1203-1214, 2017. PMID- 27002478 TI - Low-Voltage Complementary Electronics from Ion-Gel-Gated Vertical Van der Waals Heterostructures. AB - Low-voltage complementary circuits comprising n-type and p-type van der Waals heterojunction vertical field-effect transistors (VFETs) are demonstrated. The resulting VFETs possess high on-state current densities (>3000 A cm(-2) ) and on/off current ratios (>10(4) ) in a narrow voltage window (<3 V). PMID- 27002479 TI - Evolutionary engineering of Geobacillus thermoglucosidasius for improved ethanol production. AB - The ability to grow at high temperatures makes thermophiles attractive for many fermentation processes. In this work, we used evolutionary engineering to increase ethanol production in the thermophile Geobacillus thermoglucosidasius. This bacterium is a facultative anaerobe, grows at an optimal temperature of 60 degrees C, and can ferment diverse carbohydrates. However, it natively performs mixed-acid fermentation. To improve ethanol productivity, we first eliminated lactate and formate production in two strains of G. thermoglucosidasius, 95A1 and C56-YS93. These deletion strains were generated by selection on spectinomycin, which represents, to the best of our knowledge, the first time this antibiotic has been shown to work with thermophiles. Both knockout strains, however, were unable to grow under microaerobic conditions. We were able to recover growth in G. thermoglucosidasius 95A1 by serial adaptation in the presence of acetic acid. The evolved 95A1 strain was able to efficiently produce ethanol during growth on glucose or cellobiose. Genome sequencing identified loss-of-function mutations in adenine phosphoribosyltransferase (aprt) and the stage III sporulation protein AA (spoIIIAA). Disruption of both genes improved ethanol production in the unadapted strains: however, the increase was significant only when aprt was deleted. In conclusion, we were able to engineer a strain of G. thermoglucosidasius to efficiently produce ethanol from glucose and cellobiose using a combination of metabolic engineering and evolutionary strategies. This work further establishes this thermophile as a platform organism for fuel and chemical production. Biotechnol. Bioeng. 2016;113: 2156-2167. (c) 2016 Wiley Periodicals, Inc. PMID- 27002480 TI - Identification of ganglioside GM2 activator playing a role in cancer cell migration through proteomic analysis of breast cancer secretomes. AB - Cancer cell secretomes are considered a potential source for the discovery of cancer markers. In this study, the secretomes of four breast cancer (BC) cell lines (Hs578T, MCF-7, MDA-MB-231, and SK-BR-3) were profiled with liquid chromatography-tandem mass spectrometry analysis. A total of 1410 proteins were identified with less than 1% false discovery rate, of which approximately 55% (796 proteins) were predicted to be secreted from cells. To find BC-specific proteins among the secreted proteins, data of immunohistochemical staining compiled in the Human Protein Atlas were investigated by comparing the data of BC tissues with those of normal tissues. By applying various criteria, including higher expression level in BC tissues, higher predicted potential of secretion, and sufficient number of tandem mass spectra, 12 biomarker candidate proteins including ganglioside GM2 activator (GM2A) were selected for confirmation. Western blot analysis and ELISA for plasma samples of healthy controls and BC patients revealed elevation of GM2A in BC patients, especially those who were estrogen receptor-negative. Additionally, siRNA-mediated knockdown of GM2A in BC cells decreased migration in vitro, whereas the overexpression of GM2A led to an increase in cell migration. Although GM2A as a diagnostic and prognostic marker in BC should be carefully verified further, this study has established the potential role of GM2A in BC progression. PMID- 27002481 TI - Impact of p16 expression, nodal status, and smoking on oncologic outcomes of patients with head and neck unknown primary squamous cell carcinoma. AB - BACKGROUND: The prognostic significance of human papillomavirus (HPV) in the context of head and neck squamous cell carcinoma (HNSCC) of cancer of unknown primary (CUP) origin is unclear. METHODS: Patients treated for CUP at the Princess Margaret Cancer Centre between 2001 and 2013 were stratified by p16 status and retrospectively reviewed. RESULTS: Of the 73 patients included, those with p16-positive tumors (63%) had less advanced nodal status (N1-N2b; 52% vs 89%; p = .035) and less aggressive treatment. Patients with p16-positive tumors had improved 3-year disease-free survival (DFS; 79% vs 56%; p = .012) independent of nodal status and treatment in multivariable analysis (hazard ratio [HR] = 0.27; 95% confidence interval [CI] = 0.08-0.95). CONCLUSION: Among patients with CUP, p16-positive status is an independent predictor of DFS but not overall survival (OS). (c) 2016 Wiley Periodicals, Inc. Head Neck, 2016 (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1347-1353, 2016. PMID- 27002482 TI - Coral-Inspired Nanoengineering Design for Long-Cycle and Flexible Lithium-Ion Battery Anode. AB - Conversion reaction electrode materials (CREMs) have gained significant interest in lithium-ion batteries (LIBs) owing to their high theoretical gravimetric capacity. However, traditional CREMs-based electrodes, with large strain arising from Li(+) intercalation/deintercalation causes pulverization or electrical breakdown and cracking of the active materials which leads to structural collapse, limiting performance. Therefore, in order to construct electrodes with a strong tolerance to the strain incurred during the conversion reaction process, we design a coral-like three-dimensional (3D) hierarchical heterostructure by using cross-linked nanoflakes interspersed with nanoparticles (NPs) standing vertically on graphene foam (GF). The coral-like 3D hierarchical heterostructures can efficiently disperse the strain from both internal and external forces as well as increase the specific surface area for enhanced electrochemical reactions. These features lead to long-cycle stability and excellent flexibility in LIBs. Fe3O4 NPs and CoO NFs are utilized as a model system to demonstrate our strategy. The as-prepared coral-like hierarchical electrode is studied as an anode in LIBs for the first time and is shown to deliver a high reversible specific gravimetric capacity of ~1200 mA h g(-1) at a rate of 0.5 A g(-1) for 400 cycles. In addition, our batteries can even power a green light-emitting diode when bent to high degrees confirming the excellent flexibility of the material. PMID- 27002483 TI - Hysteresis in Carbon Nanotube Transistors: Measurement and Analysis of Trap Density, Energy Level, and Spatial Distribution. AB - We present a measurement technique, which we call the Pulsed Time-Domain Measurement, for characterizing hysteresis in carbon nanotube field-effect transistors, and demonstrate its applicability for a broad range of 1D and 2D nanomaterials beyond carbon nanotubes. The Pulsed Time-Domain Measurement enables the quantification (density, energy level, and spatial distribution) of charged traps responsible for hysteresis. A physics-based model of the charge trapping process for a carbon nanotube field-effect transistor is presented and experimentally validated using the Pulsed Time-Domain Measurement. Leveraging this model, we discover a source of traps (surface traps) unique to devices with low-dimensional channels such as carbon nanotubes and nanowires (beyond interface traps which exist in today's silicon field-effect transistors). The different charge trapping mechanisms for interface traps and surface traps are studied based on their temperature dependencies. Through these advances, we are able to quantify the interface trap density for carbon nanotube field-effect transistors (~3 * 10(13) cm(-2) eV(-1) near midgap), and compare this against a range of previously studied dielectric/semiconductor interfaces. PMID- 27002484 TI - Vascular imaging with contrast agent in hard and soft tissues using microcomputed tomography. AB - Vascularization is essential for many tissues and is a main requisite for various tissue-engineering strategies. Different techniques are used for highlighting vasculature, in vivo and ex vivo, in 2-D or 3-D including histological staining, immunohistochemistry, radiography, angiography, microscopy, computed tomography (CT) or micro-CT, both stand-alone and synchrotron system. Vascularization can be studied with or without a contrast agent. This paper presents the results obtained with the latest Skyscan micro-CT (Skyscan 1272, Bruker, Belgium) following barium sulphate injection replacing the bloodstream in comparison with results obtained with a Skyscan In Vivo 1076. Different hard and soft tissues were perfused with contrast agent and were harvested. Samples were analysed using both forms of micro-CT, and improved results were shown using this new micro-CT. This study highlights the vasculature using micro-CT methods. The results obtained with the Skyscan 1272 are clearly defined compared to results obtained with Skyscan 1076. In particular, this instrument highlights the high number of small vessels, which were not seen before at lower resolution. This new micro-CT opens broader possibilities in detection and characterization of the 3-D vascular tree to assess vascular tissue engineering strategies. PMID- 27002485 TI - Multifractal characterization of morphology of human red blood cells membrane skeleton. AB - The purpose of this paper is to show applicability of multifractal analysis in investigations of the morphological changes of ultra-structures of red blood cells (RBCs) membrane skeleton measured using atomic force microscopy (AFM). Human RBCs obtained from healthy and hypertensive donors as well as healthy erythrocytes irradiated with neutrons (45 MUGy) were studied. The membrane skeleton of the cells was imaged using AFM in a contact mode. Morphological characterization of the three-dimensional RBC surfaces was realized by a multifractal method. The nanometre scale study of human RBCs surface morphology revealed a multifractal geometry. The generalized dimensions Dq and the singularity spectrum f(alpha) provided quantitative values that characterize the local scale properties of their membrane skeleton organization. Surface characterization was made using areal ISO 25178-2: 2012 topography parameters in combination with AFM topography measurement. The surface structure of human RBCs is complex with hierarchical substructures resulting from the organization of the erythrocyte membrane skeleton. The analysed AFM images confirm a multifractal nature of the surface that could be useful in histology to quantify human RBC architectural changes associated with different disease states. In case of very precise measurements when the red cell surface is not wrinkled even very fine differences can be uncovered as was shown for the erythrocytes treated with a very low dose of ionizing radiation. PMID- 27002486 TI - Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors. AB - The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophysical assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD = 15 MUM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent selectivity against human drug-metabolizing P450s. Analysis of the factors governing ligand potency and selectivity using X-ray crystallography, UV-vis spectroscopy, and native mass spectrometry provides insight for subsequent drug development. PMID- 27002487 TI - Antiferromagnetism in a Family of S = 1 Square Lattice Coordination Polymers NiX2(pyz)2 (X = Cl, Br, I, NCS; pyz = Pyrazine). AB - The crystal structures of NiX2(pyz)2 (X = Cl (1), Br (2), I (3), and NCS (4)) were determined by synchrotron X-ray powder diffraction. All four compounds consist of two-dimensional (2D) square arrays self-assembled from octahedral NiN4X2 units that are bridged by pyz ligands. The 2D layered motifs displayed by 1-4 are relevant to bifluoride-bridged [Ni(HF2)(pyz)2]EF6 (E = P, Sb), which also possess the same 2D layers. In contrast, terminal X ligands occupy axial positions in 1-4 and cause a staggered packing of adjacent layers. Long-range antiferromagnetic (AFM) order occurs below 1.5 (Cl), 1.9 (Br and NCS), and 2.5 K (I) as determined by heat capacity and muon-spin relaxation. The single-ion anisotropy and g factor of 2, 3, and 4 were measured by electron-spin resonance with no evidence for zero-field splitting (ZFS) being observed. The magnetism of 1-4 spans the spectrum from quasi-two-dimensional (2D) to three-dimensional (3D) antiferromagnetism. Nearly identical results and thermodynamic features were obtained for 2 and 4 as shown by pulsed-field magnetization, magnetic susceptibility, as well as their Neel temperatures. Magnetization curves for 2 and 4 calculated by quantum Monte Carlo simulation also show excellent agreement with the pulsed-field data. Compound 3 is characterized as a 3D AFM with the interlayer interaction (J?) being slightly stronger than the intralayer interaction along Ni-pyz-Ni segments (J(pyz)) within the two-dimensional [Ni(pyz)2](2+) square planes. Regardless of X, J(pyz) is similar for the four compounds and is roughly 1 K. PMID- 27002488 TI - Sociodemographic characteristics, risk factors and psychobehavioral disorders associated to alcohol consumption in adolescents of Veneto. AB - BACKGROUND: This study aims to estimate the alcohol consumption in a large student population in Veneto (North Italy) and to identify possible psychosocial factors associated, with particular attention to the relationship between alcohol consumption and psychopathological vulnerability. METHODS: Two semi-structured questionnaires were administered: the Questionnaire for Adolescents' Saturday evening, ad hoc designed for the study, which investigates the habits and alcohol consumption patterns, and the Youth Self Report which assesses the possible presence of psychic and behavioral problems. We recruited 10,465 students attending secondary and high schools in two Venetian provinces (age range 11-19 years). Frequency and amount of alcohol consumption were analyzed in relation to socio-demographic characteristics, habits, and vulnerability to psycho-behavioral problems. RESULTS: Data confirmed the high occurrence of alcohol consumption among young people (36.5%), with a higher prevalence among males (58,0%); the frequency of consumption and the amount of alcohol in taking increase with age, in greater measure after the transition to higher education level (10.4% in secondary school, 36,% in first year till 50% in third year of high school). Alcohol misuse was associated with: pubs and clubs attendance, coming back home late, a greater availability of money and externalizing behavioral problems. CONCLUSIONS: Results from this study confirmed the worrying data about the prevalence of alcohol misuse among young people, pointing out some protective and risk factors to be taken into account in planning of preventive interventions. PMID- 27002489 TI - Adolescence, imperceptible boundary between normality and pathology: a literature review. AB - A reorganization of the brain occurs in adolescence and it is documented by neuroimaging, neurophysiology and pathology of development. The high levels of neural plasticity allow the intellectual and emotional development during adolescence, a transition period of life full of physical and psychological changes. However, potentially dangerous agents could be the genesis of psychopathology of the adult and mental illness or distress. Adolescence is a crucial phase for the maturation of the brain. Therefore, future research should study how the environment affects and influences the function and the organization of the brain. Teenagers look for new experiences and strong emotions, sometimes endangering their health. Neuroscientific explanations have been proposed for the typical teenagers' behavior. In the postnatal period the highest density of gray matter can be found in the primary sensorimotor cortex, while prefrontal cortex matures later. Subcortical areas of the brain, especially the limbic system and the reward system, develop earlier; therefore, there is an imbalance between the more mature subcortical areas and the less mature prefrontal areas during adolescence. This could explain the typical behavior patterns of this period of life. PMID- 27002490 TI - Validity of a Simple Method for Measuring Force-Velocity-Power Profile in Countermovement Jump. AB - PURPOSE: To analyze the reliability and validity of a simple computation method to evaluate force (F), velocity (v), and power (P) output during a countermovement jump (CMJ) suitable for use in field conditions and to verify the validity of this computation method to compute the CMJ force-velocity (F-v) profile (including unloaded and loaded jumps) in trained athletes. METHODS: Sixteen high-level male sprinters and jumpers performed maximal CMJs under 6 different load conditions (0-87 kg). A force plate sampling at 1000 Hz was used to record vertical ground-reaction force and derive vertical-displacement data during CMJ trials. For each condition, mean F, v, and P of the push-off phase were determined from both force-plate data (reference method) and simple computation measures based on body mass, jump height (from flight time), and push off distance and used to establish the linear F-v relationship for each individual. RESULTS: Mean absolute bias values were 0.9% (+/- 1.6%), 4.7% (+/- 6.2%), 3.7% (+/- 4.8%), and 5% (+/- 6.8%) for F, v, P, and slope of the F-v relationship (SFv), respectively. Both methods showed high correlations for F-v profile-related variables (r = .985-.991). Finally, all variables computed from the simple method showed high reliability, with ICC >.980 and CV <1.0%. CONCLUSIONS: These results suggest that the simple method presented here is valid and reliable for computing CMJ force, velocity, power, and F-v profiles in athletes and could be used in practice under field conditions when body mass, push-off distance, and jump height are known. PMID- 27002491 TI - The adrenal specific toxicant mitotane directly interacts with lipid membranes and alters membrane properties depending on lipid composition. AB - Mitotane (o,p'.-DDD) is an orphan drug approved for the treatment of adrenocortical carcinoma. The mechanisms, which are responsible for this activity of the drug, are not completely understood. It can be hypothesized that an impact of mitotane is mediated by the interaction with cellular membranes. However, an interaction of mitotane with (lipid) membranes has not yet been investigated in detail. Here, we characterized the interaction of mitotane and its main metabolite o,p'-dichlorodiphenyldichloroacetic acid (o,p'-DDA) with lipid membranes by applying a variety of biophysical approaches of nuclear magnetic resonance, electron spin resonance, and fluorescence spectroscopy. We found that mitotane and o,p'-DDA bind to lipid membranes by inserting into the lipid-water interface of the bilayer. Mitotane but not o,p'-DDA directly causes a disturbance of bilayer structure leading to an increased permeability of the membrane for polar molecules. Mitotane induced alterations of the membrane integrity required the presence of phosphatidylethanolamine and/or cholesterol. Collectively, our data for the first time characterize the impact of mitotane on the lipid membrane structure and dynamics, which may contribute to a better understanding of specific mitotane effects and side effects. PMID- 27002492 TI - Electromechanically Tunable Suspended Optical Nanoantenna. AB - Coupling mechanical degrees of freedom with plasmonic resonances has potential applications in optomechanics, sensing, and active plasmonics. Here we demonstrate a suspended two-wire plasmonic nanoantenna acting like a nanoelectrometer. The antenna wires are supported and electrically connected via thin leads without disturbing the antenna resonance. As a voltage is applied, equal charges are induced on both antenna wires. The resulting equilibrium between the repulsive Coulomb force and the restoring elastic bending force enables us to precisely control the gap size. As a result the resonance wavelength and the field enhancement of the suspended optical nanoantenna can be reversibly tuned. Our experiments highlight the potential to realize large bandwidth optical nanoelectromechanical systems. PMID- 27002493 TI - An evaluation of materials and methods for vapour measurement of the isotopic composition of pore water in deep, unsaturated zones. AB - The development of in situ vapour sampling methods to measure delta(2)H and delta(18)O in pore water of deep, unsaturated soil profiles, including mine tailings and waste rock, is required to improve our ability to track water migration through these deposits. To develop appropriate field sampling methods, a laboratory study was first undertaken to evaluate potential materials and sampling methods to collect and analyse vapour samples from unsaturated mine waste. Field methods were developed based on these findings and tested at two mine sites using either on-site analyses with a portable isotope laser spectrometer or sample collection and storage prior to laboratory analyses. The field sites included a series of deep (>50 m) multiport profiles within a coal waste rock dump and open wells installed in a sand tailings dyke at an oil sands mine. Laboratory results show that memory effects in sample bags and tubing require 3-5 pore volumes of vapour flushing prior to sample collection and sample storage times are limited to 24 h. Field sampling highlighted a number of challenges including the need to correct for sample humidity and in situ temperature. Best results were obtained when a portable laser spectrometer was used to measure vapour samples in situ. PMID- 27002494 TI - The effects of alpha-tocopherol administration in chronically lead exposed workers. AB - The aim of the study was to investigate whether alpha-tocopherol supplementation for workers who are chronically exposed to lead would normalize/improve the values of parameters that are associated with the lead-induced oxidative stress. Study population included chronically lead exposed males who were divided into two groups. Workers in the first group (reference group) were not given any antioxidants, while workers in the second group (alphaT group) received supplementation with alpha-tocopherol. After treatment, the blood lead and leukocyte malondialdehyde levels decreased significantly in the alphaT group compared to the baseline levels and reference group. However, the erythrocyte malondialdehyde, conjugated dienes, and lipofuscin levels significantly increased compared to the baseline levels. The glutathione level significantly increased compared with the baseline. Effects of supplementation with alpha-tocopherol on oxidative damage were not satisfactory. Therefore, there is no reason to administer alpha-tocopherol to workers chronically exposed to lead as a prophylaxis of lead poisoning. PMID- 27002495 TI - Perceived autonomy support, psychological needs satisfaction, depressive symptoms and apathy in French hospitalized older people. AB - Based on the self-determination theory, the aim of the present study was (1) to provide a better understanding of older people's psychological needs satisfaction in geriatric care units, then to link this information with depressive symptoms and apathy; (2) to examine whether the perceived autonomy support from health care professionals differs between needs satisfaction profiles; and (3) to investigate for all participants how each need satisfaction was related to depressive symptoms and apathy. Participants (N=100; Mage=83.33years, SD=7.78, 61% female) completed the measures of psychological needs satisfaction, perceived autonomy support, geriatric depression and apathy. Sociodemographic data were also collected. Cluster analyses showed three distinct profiles: one profile with low-moderate need satisfaction, one profile with high-moderate need satisfaction and one profile with high need satisfaction. These profiles are distinct, and did not differ in terms of participants' characteristics, except gender. Multivariate analysis of covariance (MANCOVA) revealed that participants with low-moderate need satisfaction profile have significantly higher level of depressive symptoms and apathy, and lower levels of perceived autonomy support than participants of the two other profiles. Moreover, for all participants, regression analyses revealed that both competence and relatedness needs satisfaction significantly and negatively explained 28% of the variance in depressive symptoms score and 44% of the variance in apathy score. Our results highlight the interest to examine more thoroughly the variables fostering autonomy-supportive environment in geriatric care units, and to deepen the relationship between competence and relatedness needs satisfaction and depressive symptoms and apathy. PMID- 27002496 TI - [In Process Citation]. PMID- 27002497 TI - Pediatric Oncologic Imaging: A Key Application of Combined PET/MRI. AB - Pediatric imaging has been identified as a key application of combined whole-body PET/MRI. First studies have revealed the clinical feasibility and possible advantages of PET/MRI over PET/CT and MRI. Besides a significant reduction in radiation exposure of about 50 - 75 %, combined whole-body PET/MRI offers the diagnostic advantage of the multiparametric characterization of pathophysiologic processes and helps reduce the number of necessary imaging studies. However, very few studies focusing on pediatric PET/MRI have been published to date. Additional studies are necessary in order to fully appreciate the clinical impact of this novel method. This review article shall summarize the existing literature concerning pediatric PET/MRI and give insight into the practical experience derived from over 160 pediatric PET/MRI examinations that were performed in Tubingen. KEY POINTS: *Combined PET/MR is a promising imaging modality in pediatric oncology. *Using combined PET/MRI, diagnostic radiation exposure of pediatric patients and the number of necessary imaging studies can be reduced. *Further clinical studies are necessary in order to define specific indications for combined PET/MRI in pediatric radiology. PMID- 27002498 TI - Use of Paclitaxel-Coated Balloon Catheter Dilation to Reduce In-Stent Restenosis in Transjugular Intrahepatic Portosystemic Shunt (TIPS). AB - PURPOSE: Paclitaxel-coated balloons (PCB) inhibit neointimal proliferation in arteries. The purpose of this retrospective analysis was to investigate the effect of PCB in in-stent restenosis after transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhotic liver disease. MATERIALS AND METHODS: Six patients (mean age: 65 +/- 10 years) with recurrent in-stent restenoses in TIPS (5 bare stents, 1 covered stent) underwent a single percutaneous transluminal angioplasty (PTA) with PCB (3 ug paclitaxel/mm(2)). Post-interventional outcome and patency were compared with those of prior plain optimal balloon angioplasty (POBA) in the same patients. During a two-year follow up period, all patients underwent angiographic examinations at 6-month intervals. In-stent minimal lumen diameter (MLD) and late lumen loss (LLL) were assessed. Paclitaxel residues on balloon and sheath surfaces as well as venous plasma concentrations (0 - 24 hours) were analyzed. RESULTS: PCB decreased the need for clinically driven repeat PTA (POBA: 53 % of angiographic examinations; paclitaxel PTA: 19 %; P = 0.014). LLL/diameter stenosis was higher after POBA (2.4 +/- 1.5 mm/28 +/- 18 %) than after PCB (0.5 +/- 0.8 mm/7 +/- 11 %, P = 0.029). Residual paclitaxel on balloons was 28 +/- 9 % of dose and 0.2 +/- 0.1 % on sheath surfaces. Paclitaxel plasma concentrations were below detectable levels throughout the first 24 hours after the interventions in all patients. The procedure was well tolerated and no clinical side effects attributable to paclitaxel were observed. CONCLUSION: In patients with recurrent in-stent stenoses, a single PTA with PCB resulted in a prolonged secondary patency due to pseudointimahyperplasia without a systemic effect of paclitaxel. KEY POINTS: *Intimahyperplasia is a common reason for long-time TIPS dysfunction. *First-in man local paclitaxel application in TIPS patients with recurrent in-stent stenoses. *PTA with PCB resulted in a prolonged secondary patency compared to POBA. *No systemic effects of Paclitaxel were detected. PMID- 27002499 TI - Systemic immunodominant CD8 responses with an effector-like phenotype are induced by intravaginal immunization with attenuated HSV vectors expressing HIV Tat and mediate protection against HSV infection. AB - Mucosal HSV infection remains a public health issue in developing and developed world. However, an effective vaccine is still missing, partly because of the incomplete knowledge of correlates of protection. In this study we have investigated the kinetics and quality of immunity elicited by an attenuated HSV1 vector expressing the immunomodulatory Tat protein of HIV-1 (HSV1-Tat). Animals were immunized by intravaginal (IVag) or intradermal (ID) route with HSV1-Tat or with a control HSV1 vector expressing the LacZ gene (HSV1-LacZ) and immune responses were characterized in different anatomical districts. IVag immunization with HSV1-Tat enhanced both expansion and memory phases of HSV-specific immunodominant CD8 responses at systemic, but not local, level and induced short- and long-term protection against mucosal challenge. Conversely, ID immunization with HSV1-Tat favored HSV-subdominant CD8 responses, which protected mice only at early time points after immunization. IVag immunization, in particular with HSV1 Tat, compared to ID immunization, induced the differentiation of CD8(+) T lymphocytes into short-lived effector (SLEC) and effector memory (Tem) cells, generating more robust recall responses associated with increased control of virus replication. Notably, systemic SLEC and Tem contributed to generate protective local secondary responses, demonstrating their importance for mucosal control of HSV. Finally, IgG responses were observed mostly in IVag HSV1-Tat immunized animals, although seemed dispensable for protection, which occurred even in few IgG negative mice. Thus, HSV1 vectors expressing Tat induce protective anti-HSV1 immune responses. PMID- 27002500 TI - A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy. AB - BACKGROUND: HIV-1 specific cellular immunity plays an important role in controlling viral replication. In this first-in-human therapeutic vaccination study, a replication-defective HIV-1 vaccine (HIVAX) was tested in HIV-1 infected participants undergoing highly active antiretroviral therapy (HAART) to enhance anti-HIV immunity (Clinicaltrials.gov, identifier NCT01428596). METHODS: A010 was a randomized, placebo-controlled trial to evaluate the safety and the immunogenicity of a replication defective HIV-1 vaccine (HIVAX) given as a subcutaneous injection to HIV-1 infected participants who were receiving HAART with HIV-1 viral load <50 copies/ml and CD4 cell count >500 cells/mm(3). HIV-1 specific immune responses were monitored by INF-gamma enzyme linked immunospot (Elispot) and intracellular cytokine staining (ICS) assay after vaccination. Following the randomized placebo-controlled vaccination phase, subjects who received HIVAX vaccine and who met eligibility underwent a 12-week analytical antiretroviral treatment interruption (ATI). Viral load was monitored throughout the study. RESULTS: HIVAX was well tolerated in trial participants. Transient grade 1 to 2 (mild to moderate) injection site reactions occurred in 8 of 10 vaccinated participants. HIVAX was immunogenic in all vaccinated participants. The functionality of T cells was significantly enhanced after vaccination. Median viral load (3.45 log10 copies/ml, range of 96-12,830 copies/ml) at the end of the 12-week treatment interruption in HIVAX vaccinated group was significantly lower than the pre-treatment levels. Three vaccinated participants extended ATI for up to 2 years with stable CD4 cells and low viral loads. CONCLUSIONS: HIVAX vaccine is generally safe, elicits strong anti-HIV-1 immune responses, and may play an important role in controlling viral load during treatment interruption in HIV-1 infected participants. PMID- 27002502 TI - HIV care: A missed opportunity for immunization. PMID- 27002503 TI - On the need to wait 4 weeks between two live attenuated vaccines. PMID- 27002501 TI - Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting. AB - BACKGROUND: Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. METHODS: We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. RESULTS: Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs <= $790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs <= $444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) versus annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0% and nearly eliminated hookworm infection in children. CONCLUSION: Using a human hookworm vaccine would be cost effective and in many cases economically dominant, providing both health benefits and cost-savings. It could become a key technology in effecting control and elimination efforts for hookworm globally. PMID- 27002505 TI - Environmental estrogens have an impact on the ERs and their signaling in ER responsive tissues and organs. PMID- 27002504 TI - Epidemiological impact and cost-effectiveness of introducing vaccination against serogroup B meningococcal disease in France. AB - INTRODUCTION: Despite its low incidence in France, invasive serogroup B meningococcal disease remains a public health concern. A new vaccine against the disease, Bexsero((r)), has been licensed in the EU. We studied the epidemiological impact and cost-effectiveness of routine vaccination using Bexsero((r)) in order to inform the decision-making process regarding its potential inclusion in the vaccination schedule. METHODS: A multi-generational Markov model was used. Time horizon was set to 100 years. Five vaccination strategies were evaluated: infants at 3, 5, 6 and 13 months, toddlers at 13, 15 and 27 months and adolescents at 15 years provided 2 doses one month apart. A booster dose at 15 years old and a catch-up for 15 years old subjects during the first 15 years of the programme were added to the infant and toddler strategies. Costs per QALY gained were computed from a restricted societal perspective including direct costs only. Herd immunity was simulated in an alternative base case scenario and sensitivity analyses. RESULTS: In the base-case analysis without herd immunity and with all cohorts vaccinated, at ? 40 per vaccine dose, routine infant vaccination would provide the lowest cost per QALY gained (? 380,973) despite only preventing 18% of cases. Under the assumption of herd immunity, the adolescent vaccination would provide the lowest cost per QALY gained (? 135,902) preventing 24% of cases. Infant vaccination with a late booster and catch-up would prevent 51% of cases with a cost of ? 188,511 per QALY gained. CONCLUSIONS: Given current meningococcal epidemiology in France and the available data on the protection provided by Bexsero((r)), our modelling work showed that routine vaccination against serogroup B meningococcal disease is not cost-effective. PMID- 27002506 TI - Revisiting dosing regimen using PK/PD modeling: the MODEL1 phase I/II trial of docetaxel plus epirubicin in metastatic breast cancer patients. AB - The MODEL1 trial is the first model-driven phase I/II dose-escalation study of densified docetaxel plus epirubicin administration in metastatic breast cancer patients, a regimen previously known to induce unacceptable life-threatening toxicities. The primary objective was to determine the maximum tolerated dose of this densified regimen. Study of the efficacy was a secondary objective. Her2 negative, hormone-resistant metastatic breast cancer patients were treated with escalating doses of docetaxel plus epirubicin every 2 weeks for six cycles with granulocyte colony stimulating factor support. A total of 16 patients were treated with total doses ranging from 85 to 110 mg of docetaxel plus epirubicin per cycle. Dose escalation was controlled by a non-hematological toxicity model. Dose densification was guided by a model of neutrophil kinetics, able to optimize docetaxel plus epirubicin dosing with respect to pre-defined acceptable levels of hematological toxicity while ensuring maximal efficacy. The densified treatment was safe since hematological toxicity was much lower compared to previous findings, and other adverse events were consistent with those observed with this regimen. The maximal tolerated dose was 100 mg given every 2 weeks. The response rate was 45 %; median progression-free survival was 10.4 months, whereas 54.6 months of median overall survival was achieved. The optimized docetaxel plus epirubicin dosing regimen led to fewer toxicities associated with higher efficacy as compared with standard or empirical densified dosing. This study suggests that model-driven dosage adjustment can lead to improved efficacy-toxicity balance in patients with cancer when several anticancer drugs are combined. PMID- 27002507 TI - Equivalence of MammaPrint array types in clinical trials and diagnostics. AB - MammaPrint is an FDA-cleared microarray-based test that uses expression levels of the 70 MammaPrint genes to assess distant recurrence risk in early-stage breast cancer. The prospective RASTER study proved that MammaPrint Low Risk patients can safely forgo chemotherapy, which is further subject of the prospective randomized MINDACT trial. While MammaPrint diagnostic results are obtained from mini-arrays, clinical trials may be performed on whole-genome arrays. Here we demonstrate the equivalence and reproducibility of the MammaPrint test. MammaPrint indices were collected for breast cancer samples: (i) on both customized certified array types (n = 1,897 sample pairs), (ii) with matched fresh and FFPE tissues (n = 552 sample pairs), iii) for control samples replicated over a period of 10 years (n = 11,333), and iv) repeated measurements (n = 280). The array type indicated a near perfect Pearson correlation of 0.99 (95 % CI: 0.989-0.991). Paired fresh and FFPE samples showed an excellent Pearson correlation of 0.93 (95 % CI 0.92-0.94), in spite of the variability introduced by intratumoral tissue heterogeneity. Control samples showed high consistency over 10 year's time (overall reproducibility of 97.4 %). Precision and repeatability are overall 98.2 and 98.3 %, respectively. Results confirm that the combination of the near perfect correlation between array types, excellent equivalence between tissue types, and a very high stability, precision, and repeatability demonstrate that results from clinical trials (such as MINDACT and I-SPY 2) are equivalent to current MammaPrint FFPE and fresh diagnostics, and can be used interchangeably. PMID- 27002508 TI - Effectiveness of bisphosphonate use and risk of contralateral breast cancer and recurrence in women with early-stage breast cancer treated with tamoxifen. AB - The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781 women diagnosed with early-stage breast cancer from 1996 to 2007, treated with tamoxifen, and followed through December 31, 2009 at Kaiser Permanente Northern California (KPNC, n = 8857) and Southern California (KPSC, n = 7924). Sociodemographic, clinical, and pharmacy information were extracted from electronic medical records and cancer registries. CBC was identified from cancer registries, and recurrences from electronic health records and chart reviews. Multivariate Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) treating BP use and hormonal therapy as time-varying variables. After mean 6.4 years of follow-up, 494 (3.0 %) women developed CBC. BP use post-breast cancer diagnosis (>93 % alendronate) ranged from 14.5 to 24.9 % at both study sites. Overall, there was no association of BP use with reduced risk of CBC (ever use, HR = 0.96; 95 % CI 0.67-1.38 and continuous use, HR = 1.03; 95 % CI 0.88, 1.20). Similar null associations were observed for recurrence (ever use, HR = 0.98; 95 % CI 0.82, 1.17 and continuous use, HR = 1.00; 95 % CI 0.92, 1.09). Associations varied somewhat by site yet confidence intervals overlapped. BP use was not associated with reduced risk of recurrence or new primary disease among women diagnosed with early breast cancer and treated with tamoxifen. PMID- 27002510 TI - Impact of migraine on fibromyalgia symptoms. AB - BACKGROUND: Fibromyalgia (FMS) and high frequency episodic/chronic migraine (M) very frequently co-occur, suggesting common pathophysiological mechanisms; both conditions display generalized somatic hyperalgesia. In FMS-M comorbidity we assessed if: a different level of hyperalgesia is present compared to one condition only; hyperalgesia is a function of migraine frequency; migraine attacks trigger FMS symptoms. METHODS: Female patients with fibromyalgia (FMS)(n.40), high frequency episodic migraine (M1)(n.41), chronic migraine (M2)(n.40), FMS + M1 (n.42) and FMS + M2 (n.40) underwent recording of: electrical pain thresholds in skin, subcutis and muscle and pressure pain thresholds in control sites, -pressure pain thresholds in tender points (TePs), number of monthly migraine attacks and fibromyalgia flares (3-month diary). Migraine and FMS parameters were evaluated before and after migraine prophylaxis, or no prophylaxis, for 3 months with calcium-channel blockers, in two further FMS + H1 groups (n.49, n.39). 1-way ANOVA was applied to test trends among groups, Student's t-test for paired samples was used to compare pre and post-treatment values. RESULTS: The lowest electrical and pressure thresholds at all sites and tissues were found in FMS + M2, followed by FMS + H1, FMS, M2 and M1 (trend: p < 0.0001). FMS monthly flares were progressively higher in FMS, FMS + M1 and FMS + M2 (p < 0.0001); most flares (86-87 %) occurred within 12 h from a migraine attack in co-morbid patients (p < 0.0001). Effective migraine prophylaxis vs no prophylaxis also produced a significant improvement of FMS symptoms (decreased monthly flares, increased pain thresholds)(0.0001 < p < 0.003). CONCLUSIONS: Co morbidity between fibromyalgia and migraine involves heightened somatic hyperalgesia compared to one condition only. Increased migraine frequency - with shift towards chronicity - enhances both hyperalgesia and spontaneous FMS pain, which is reversed by effective migraine prophylaxis. These results suggest different levels of central sensitization in patients with migraine, fibromyalgia or both conditions and a role for migraine as a triggering factor for FMS. PMID- 27002509 TI - Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity. AB - Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochondria-targeted antioxidant Mito-Tempo (MT) was given 1.5 h later. APAP caused severe liver injury in mice, as indicated by the increase in plasma ALT activities and centrilobular necrosis. MT dose-dependently reduced the injury. Importantly, MT did not affect APAP-protein adducts formation, glutathione depletion or c-jun N-terminal kinase activation and its mitochondrial translocation. In contrast, hepatic glutathione disulfide and peroxynitrite formation were dose-dependently reduced by MT, indicating its effective mitochondrial oxidant stress scavenging capacity. Consequently, mitochondrial translocation of Bax and release of mitochondrial intermembrane proteins such as apoptosis-inducing factor were prevented, and nuclear DNA fragmentation was eliminated. To demonstrate the importance of mitochondria specific antioxidant property of MT, we compared its efficacy with Tempo, which has the same pharmacological mode of action as MT but lacks the mitochondria targeting moiety. In contrast to the dramatic protection by MT, the same molar dose of Tempo did not significantly reduce APAP hepatotoxicity. In contrast, even a 3 h post-treatment with MT reduced 70 % of the injury, and the combination of MT with N-acetylcysteine (NAC) provided superior protection than NAC alone. We conclude that MT protects against APAP overdose in mice by attenuating the mitochondrial oxidant stress and preventing peroxynitrite formation and the subsequent mitochondrial dysfunction. MT is a promising therapeutic agent for APAP overdose patients. PMID- 27002511 TI - Socioeconomic value of intervention for chronic pain. AB - PURPOSE: The purpose of this study was to examine the cost-effectiveness of pain treatments in two pain centers in Japan. METHODS: The study population comprised 91 patients receiving various treatments for chronic pain, which were divided into three categories: (1) medication, (2) medication + nerve block, and (3) other modalities (exercise and/or pain education). Pain was assessed using the Pain Disability Assessment Scale (PDAS) score, Hospital Anxiety and Depression Scale (HADS) score, Pain Catastrophizing Scale (PCS) score, and EQ-5D score. First, the reliability of the EQ-5D score first assessed by evaluating the correlation this score with those of the other pain-related evaluation instruments, and then the cost effectiveness of the pain treatments was evaluated. Evaluation of medical costs was based on data provided from the Management Services of the hospital, which in turn were based on national health scheme medical treatment fees. The quality-adjusted life year (QALY) value was calculated from the EQ-5D score, converted to 12 months, and then used for cost benefit analysis along with medical treatment fees. RESULTS: According to the recent IASP classification, more patients had chronic neuropathic pain (41) than chronic primary pain (37 patients) or chronic musculoskeletal pain (27 patients). There was a significant correlation between the EQ-5D score and the PDAS, HADS, and PCS scores, which demonstrated the reliability of the EQ-5D score. Significant improvement in the HADS, PCS, and EQ-5D scores was noted after 3 months of pain treatment. Calculation of the cost-effectiveness based on the estimated annual medical treatment cost and QALY revealed a mean value of US $45,879 +/- 103,155 per QALY (median US $16,903), indicating adequate socioeconomic utility. CONCLUSION: Based on our results, the EQ-5D is reliable for evaluating chronic pain in patients. The medico-economic balance was appropriate for all treatments provided in two comprehensive pain centers in Japan. PMID- 27002512 TI - Healthy Skin: Cancer Education for School Teachers and Nurses Using a "Train and Equip" Method. AB - Skin cancer, especially malignant melanoma, continues on the increase. Different interventions are attempting to impact on this problem. The approach used by the Partners in Health Sciences program at the University of Arkansas for Medical Science is to both "train" and, importantly, "equip" classroom teachers and school nurses in a "Healthy Skin" professional development curriculum. Each participant not only received face-to-face interactive content training in a workshop setting that lasted 6 h; each also received a resource kit of supplies, materials, and equipment used in the workshop and designed for the trainee to use with students in a classroom/school setting. This single "hit" professional development event then can be replicated by each trainee annually for the span of her/his teaching/school-nursing career. A total of 588 trainees participated in "Healthy Skin" workshops that were held in 17 communities throughout the state. Participants attended from 188 different towns/cities. Of those in attendance, 511 (87 %) were females, 77 (13 %) males, 81 % Caucasian, 16 % African Americans, and the remaining 3 % self-identified as "other". There were 471 teachers, 85 nurses, and 32 "others" (administrators, school counselors). Trainees completed anonymous pre/post test measures with an increase in knowledge of 28.5 %. A short term evaluation was conducted at the end of the workshop. After a minimum of 6 months had elapsed, a long-term evaluation was used to capture data on how the workshop experience transferred into new curricular/learning activities for the students of the workshop participants. There was a high level of satisfaction with the workshop experience and use of workshop content and resource kits. Our experiences in this type of professional development outreach provide a model of how institutions of higher education could contribute to the professional development of K-12 teachers and their students in any content area. PMID- 27002513 TI - Dual Degrees in Medicine: Options for Medical Students. AB - Increasingly, more universities are showing an interest in offering combined degrees (most commonly research-based) with their medical degree. Intercalated degrees often require the medical student to take time off their medical course in order to pursue the second degree full-time. Concurrent degrees, on the other hand, do not usually require taking additional time to complete; rather, they are integrated into the medical curriculum. Exposing medical students to the array of opportunities offered by their academic institutions will hopefully allow interested students to pursue studies in an area of their preference, at a pace of their own and for a cost (time and financial) they could afford. This article explores the different degrees offered around the world to students in combination with medical degrees. PMID- 27002514 TI - Modelling the fear effect in predator-prey interactions. AB - A recent field manipulation on a terrestrial vertebrate showed that the fear of predators alone altered anti-predator defences to such an extent that it greatly reduced the reproduction of prey. Because fear can evidently affect the populations of terrestrial vertebrates, we proposed a predator-prey model incorporating the cost of fear into prey reproduction. Our mathematical analyses show that high levels of fear (or equivalently strong anti-predator responses) can stabilize the predator-prey system by excluding the existence of periodic solutions. However, relatively low levels of fear can induce multiple limit cycles via subcritical Hopf bifurcations, leading to a bi-stability phenomenon. Compared to classic predator-prey models which ignore the cost of fear where Hopf bifurcations are typically supercritical, Hopf bifurcations in our model can be both supercritical and subcritical by choosing different sets of parameters. We conducted numerical simulations to explore the relationships between fear effects and other biologically related parameters (e.g. birth/death rate of adult prey), which further demonstrate the impact that fear can have in predator-prey interactions. For example, we found that under the conditions of a Hopf bifurcation, an increase in the level of fear may alter the direction of Hopf bifurcation from supercritical to subcritical when the birth rate of prey increases accordingly. Our simulations also show that the prey is less sensitive in perceiving predation risk with increasing birth rate of prey or increasing death rate of predators, but demonstrate that animals will mount stronger anti predator defences as the attack rate of predators increases. PMID- 27002516 TI - Baked Egg and Milk Exposure as Immunotherapy in Food Allergy. AB - Baked milk and egg have the potential to act as a form of oral immunotherapy (OIT). Clinical studies have shown that a majority of milk- and egg-allergic children can tolerate these allergens modified in baked form, and immunologic changes reported in subjects ingesting baked milk and egg mirror those seen in food allergy OIT trials. In addition, several studies have indicated that resolution of milk and egg allergies occur sooner in populations regularly ingesting baked milk and egg. Oral food challenges remain the best method for determining tolerability of baked milk and egg since baseline characteristics and diagnostic testing have not been reliable predictors. In this review, we explore the tolerability of baked milk and egg and their potential as OIT treatment for milk and egg allergy. PMID- 27002517 TI - Use of Intermediate Endpoints in the Economic Evaluation of New Treatments for Advanced Cancer and Methods Adopted When Suitable Overall Survival Data are Not Available. AB - OBJECTIVES: This study assessed the use of intermediate endpoints in the economic evaluation of new treatments for advanced cancer and the methodological approaches adopted when overall survival (OS) data are unavailable or of limited use. METHODS: A systematic literature review was conducted to identify economic evaluations of treatments for advanced cancer published between 2003 and 2013. Cost-effectiveness and cost-utility analyses expressed in cost per life-year gained and cost per quality-adjusted life-year using an intermediate endpoint as an outcome measure were eligible. Characteristics of selected studies were extracted and comprised population, treatment of interest, comparator, line of treatment, study perspective, and time horizon. Use of intermediate endpoints and methods adopted when OS data were lacking were analyzed. RESULTS: In total, 7219 studies were identified and 100 fulfilled the eligibility criteria. Intermediate endpoints mostly used were progression-free survival and time to progression, accounting for 92 % of included studies. OS data were unavailable for analysis in nearly 25 % of economic evaluations. In the absence of OS data, studies most commonly assumed an equal risk of death for all treatment groups. Other methods included use of indirect comparison based on numerous assumptions, use of a proxy for OS, consultation with clinical experts, and use of published external information from different treatment settings. CONCLUSION: Intermediate endpoints are widely used in the economic evaluation of new treatments for advanced cancer in order to estimate OS. Currently, different methods are used in the absence of suitable OS data and the choice of an appropriate method depends on many factors including the data availability. PMID- 27002515 TI - Pollen Allergens for Molecular Diagnosis. AB - Pollen allergens are one of the main causes of type I allergies affecting up to 30% of the population in industrialized countries. Climatic changes affect the duration and intensity of pollen seasons and may together with pollution contribute to increased incidences of respiratory allergy and asthma. Allergenic grasses, trees, and weeds often present similar habitats and flowering periods compromising clinical anamnesis. Molecule-based approaches enable distinction between genuine sensitization and clinically mostly irrelevant IgE cross reactivity due to, e. g., panallergens or carbohydrate determinants. In addition, sensitivity as well as specificity can be improved and lead to identification of the primary sensitizing source which is particularly beneficial regarding polysensitized patients. This review gives an overview on relevant pollen allergens and their usefulness in daily practice. Appropriate allergy diagnosis is directly influencing decisions for therapeutic interventions, and thus, reliable biomarkers are pivotal when considering allergen immunotherapy in the context of precision medicine. PMID- 27002518 TI - Economic Evaluations of Opioid Use Disorder Interventions. AB - BACKGROUND: The economic costs associated with opioid misuse are immense. Effective interventions for opioid use disorders are available; however, given the scarce resources faced by substance use treatment providers and payers of all kinds, evidence of effectiveness is not always sufficient to encourage adoption of a given therapy-nor should it be. Economic evaluations can provide evidence that will help stakeholders efficiently allocate their resources. OBJECTIVE: The purpose of this study was to review the literature on economic evaluations of opioid use disorder interventions. METHODS: We performed a systematic review of the major electronic databases from inception until August 2015. A sensitive approach was used to ensure a comprehensive list of relevant articles. Given the quality of the existing reviews, we narrowed our search to studies published since 2007. The Drummond checklist was used to evaluate and categorize economic evaluation studies according to their quality. RESULTS: A total of 98 articles were identified as potentially relevant to the current study. Of these 98 articles, half (n = 49) were included in this study. Six of the included articles were reviews. The remaining 43 articles reported economic evaluation studies of interventions for opioid use disorders. In general, the evidence on methadone maintenance therapy (MMT) supports previous findings that MMT is an economically advantageous opioid use disorder therapy. The economic literature comparing MMT with other opioid use disorder pharmacotherapies is limited, as is the literature on other forms of therapy. CONCLUSION: With the possible exception of MMT, additional high-quality economic evaluations are needed in order to assess the relative value of existing opioid use disorder interventions. PMID- 27002519 TI - Cancer Drugs Fund 2.0: A Missed Opportunity? PMID- 27002520 TI - Medical effects of internal contamination with actinides: further controversy on depleted uranium and radioactive warfare. AB - The Nuclear Age began in 1945 with testing in New Mexico, USA, and the subsequent bombings of Hiroshima and Nagasaki. Regardless of attempts to limit the development of nuclear weapons, the current world arsenal has reached the staggering dimensions and presents a significant concern for the biosphere and mankind. In an explosion of a nuclear weapon, over 400 radioactive isotopes are released into the biosphere, 40 of which pose potential dangers including iodine, cesium, alkaline earths, and actinides. The immediate health effects of nuclear explosions include thermal, mechanical, and acute radiation syndrome. Long-term effects include radioactive fallout, internal contamination, and long-term genotoxicity. The current controversial concern over depleted uranium's somatic and genetic toxicity is still a subject of worldwide sustained research. The host of data generated in the past decades has demonstrated conflicting findings, with the most recent evidence showing that its genotoxicity is greater than previously considered. Of particular concern are the osteotropic properties of uranium isotopes due to their final retention in the crystals of exchangeable and nonexchangeable bone as well as their proximity to pluripotent stem cells. Depleted uranium remains an unresolved issue in both warfare and the search for alternative energy sources. PMID- 27002521 TI - The relevance of 'mixed anxiety and depression' as a diagnostic category in clinical practice. AB - According to ICD-10 criteria, mixed anxiety and depressive disorder (MADD) is characterized by co-occurring, subsyndromal symptoms of anxiety and depression, severe enough to justify a psychiatric diagnosis, but neither of which are clearly predominant. MADD appears to be very common, particularly in primary care, although prevalence estimates vary, often depending on the diagnostic criteria applied. It has been associated with similarly pronounced distress, impairment of daily living skills, and reduced health-related quality of life as fully syndromal depression and anxiety. Although about half of the patients affected remit within a year, non-remitting patients are at a high risk of transition to a fully syndromal psychiatric disorder. The validity and clinical usefulness of MADD as a diagnostic category are under debate. It has not been included in the recently released DSM-5 since the proposed diagnostic criteria turned out to be not sufficiently reliable. Moreover, reviewers have disputed the justification of MADD based on divergent results regarding its prevalence and course, diagnostic stability over time, and nosological inconsistencies between subthreshold and threshold presentations of anxiety and depressive disorders. We review the evidence in favor and against MADD and argue that it should be included into classification systems as a diagnostic category because it may enable patients to gain access to appropriate treatment early. This may help to reduce patients' distress, prevent exacerbation to a more serious psychiatric disorder, and ultimately reduce the societal costs of this very common condition. PMID- 27002522 TI - Internet-Based Interventions for Addictive Behaviours: A Systematic Review. AB - Internet-based interventions have emerged as a new treatment and intervention modality for psychological disorders. Given their features of treatment flexibility, anonymity and confidentiality, this modality may be well suited in the management of addictive behaviours. A systematic literature review of the effectiveness and treatment outcomes of Internet-based interventions for smoking cessation, problematic alcohol use, substance abuse and gambling was performed. Studies were included if they met the following criteria: clients received a structured therapeutic Internet-based intervention for a problematic and addictive behaviour; included more than five clients; effectiveness was based on at least one outcome; outcome variables were measured before and immediately following the interventions; had a follow-up period; and involved at least minimal therapist contact over the course of the program. Sixteen relevant studies were found; nine addressed the effects of Internet-based interventions on smoking cessation, four on gambling, two on alcohol and one on opioid dependence. All studies demonstrated positive treatment outcomes for their respective addictive behaviours. The current review concluded that Internet-based interventions are effective in achieving positive behavioural change through reducing problematic behaviours. This mode of therapy has been found to have the capacity to provide effective and practical services for those who might have remained untreated, subsequently reducing the barriers for help-seekers. This in turn provides imperative information to treatment providers, policy makers, and academic researchers. PMID- 27002523 TI - Cost-Effectiveness of Blood Donation Screening for Trypanosoma cruzi in Mexico. AB - An estimated 2 million inhabitants are infected with Chagas disease in Mexico, with highest prevalence coinciding with highest demographic density in the southern half of the country. After vector-borne transmission, Trypanosoma cruzi is principally transmitted to humans via blood transfusion. Despite initiation of serological screening of blood donations or donors for T. cruzi since 1990 in most Latin American countries, Mexico only finally included mandatory serological screening nationwide in official Norms in 2012. Most recent regulatory changes and segmented blood services in Mexico may affect compliance of mandatory screening guidelines. The objective of this study was to calculate the incremental cost-effectiveness ratio for total compliance of current guidelines from both Mexican primary healthcare and regular salaried worker health service institutions: the Secretary of Health and the Mexican Institute for Social Security. We developed a bi-modular model to analyze compliance using a decision tree for the most common screening algorithms for each health institution, and a Markov transition model for the natural history of illness and care. The incremental cost effectiveness ratio based on life-years gained is US$ 383 for the Secretary of Health, while the cost for an additional life-year gained is US$ 463 for the Social Security Institute. The results of the present study suggest that due to incomplete compliance of Mexico's national legislation during 2013 and 2014, the MoH has failed to confirm 15,162 T. cruzi infections, has not prevented 2,347 avoidable infections, and has lost 333,483 life-years. Although there is a vast difference in T. cruzi prevalence between Bolivia and Mexico, Bolivia established mandatory blood screening for T.cruzi in 1996 and until 2002 detected and discarded 11,489 T. cruzi -infected blood units and prevented 2,879 potential infections with their transfusion blood screening program. In the first two years of Mexico's mandated program, the two primary institutions failed to prevent due to incomplete compliance more potential infections than those gained from the first five years of Bolivia's program. Full regulatory compliance should be clearly understood as mandatory for the sake of blood security, and its monitoring and analysis in Mexico should be part of the health authority's responsibility. PMID- 27002524 TI - Can Scat Analysis Describe the Feeding Habits of Big Cats? A Case Study with Jaguars (Panthera onca) in Southern Pantanal, Brazil. AB - Large cats feeding habits have been studied through two main methods: scat analysis and the carcasses of prey killed by monitored animals. From November 2001 to April 2004, we studied jaguar predation patterns using GPS telemetry location clusters on a cattle ranch in southern Pantanal. During this period, we recorded 431 carcasses of animals preyed upon by monitored jaguars. Concurrently, we collected 125 jaguar scats opportunistically. We compared the frequencies of prey found through each method. We also compared the prey communities using Bray Curtis similarity coefficient. These comparisons allowed us to evaluate the use of scat analysis as a means to describe jaguar feeding habits. Both approaches identified prey communities with high similarity (Bray-Curtis coefficient > 70). According to either method, jaguars consume three main prey: cattle (Bos taurus), caiman (Caiman yacare) and peccaries (Tayassu pecari and Pecari tajacu). The two methods did not differ in the frequency of the three main prey over dry and wet seasons or years sampled. Our results show that scat analysis is effective and capable of describing jaguar feeding habits. PMID- 27002525 TI - In Vivo and In Vitro Detection of Luminescent and Fluorescent Lactobacillus reuteri and Application of Red Fluorescent mCherry for Assessing Plasmid Persistence. AB - Lactobacillus reuteri is a symbiont that inhabits the gastrointestinal (GI) tract of mammals, and several strains are used as probiotics. After introduction of probiotic strains in a complex ecosystem like the GI tract, keeping track of them is a challenge. The main objectives of this study were to introduce reporter proteins that would enable in vivo and in vitro detection of L. reuteri and increase knowledge about its interactions with the host. We describe for the first time cloning of codon-optimized reporter genes encoding click beetle red luciferase (CBRluc) and red fluorescent protein mCherry in L. reuteri strains ATCC PTA 6475 and R2LC. The plasmid persistence of mCherry-expressing lactobacilli was evaluated by both flow cytometry (FCM) and conventional plate count (PC), and the plasmid loss rates measured by FCM were lower overall than those determined by PC. Neutralization of pH and longer induction duration significantly improved the mCherry signal. The persistency, dose-dependent signal intensity and localization of the recombinant bacteria in the GI tract of mice were studied with an in vivo imaging system (IVIS), which allowed us to detect fluorescence from 6475-CBRluc-mCherry given at a dose of 1*1010 CFU and luminescence signals at doses ranging from 1*105 to 1*1010 CFU. Both 6475-CBRluc mCherry and R2LC-CBRluc were localized in the colon 1 and 2 h after ingestion, but the majority of the latter were still found in the stomach, possibly reflecting niche specificity for R2LC. Finally, an in vitro experiment showed that mCherry-producing R2LC adhered efficiently to the intra cellular junctions of cultured IPEC-J2 cells. In conclusion, the two reporter genes CBRluc and mCherry were shown to be suitable markers for biophotonic imaging (BPI) of L. reuteri and may provide useful tools for future studies of in vivo and in vitro interactions between the bacteria and the host. PMID- 27002526 TI - Development and recovery of histopathological alterations in the gonads of zebrafish (Danio rerio) after single and combined exposure to endocrine disruptors (17alpha-ethinylestradiol and fadrozole). AB - Exposure of wildlife to endocrine disrupting chemicals (EDCs) is not necessarily continuous. Due to seasonal changes and variable industrial and agricultural activities it often occurs intermittently. Thus, it is possible that aquatic organisms may be more affected by periodic peak exposure than by chronic exposure. Therefore, an experimental scenario including an exposure from 2h to 90 days post-fertilization (dpf) and a subsequent recovery period until 150 dpf was chosen to assess the potential reversibility of the effects of sex steroids on sexual and gonad development of zebrafish (Danio rerio). The aim of this study was to investigate the persistence of the endocrine effects of an estrogen (EE2 17alpha-ethinylestradiol, 4ng/L), an inhibitor of estrogen synthesis (Fad fadrozole, 50MUg/L) or their binary mixture (Mix-EE2+ Fad, 4ng/L+50MUg/L). Afterwards, a semi-quantitative histological assessment was used to investigate histopathological changes on gonad differentiation and development. The data showed that fadrozole, alone or in combination with EE2, permanently disrupts the sexual development, inducing masculinization and causing severe pathological alterations in testis, such as intersex associated to the enlargement of sperm ducts, interstitial changes, asynchronous development and detachment of basal membrane. After exposures to both EDCs and their mixture, the gonad histopathology revealed interstitial proteinaceous fluid deposits and, in ovaries, there were atretic oocytes, and presumably degenerative mineralization. On the other hand, the gonadal changes induced by EE2 alone seem to be partially reversible when the exposure regime changed to a recovery period. In addition, EE2 enhanced zebrafish growth in both genders, with male fish presenting signs of early obesity such as the presence of adipocytes in testis. Moreover, sex ratio was slightly skewed toward females, at 90 and 105 dpf, in zebrafish exposed to EE2. The data further indicate that long-term studies on impacts of single EDCs and their mixtures with recovery periods are crucial to reveal the possibility of sex reversal and pathological changes of gonads that can adversely affect breeding. PMID- 27002528 TI - Migration, Remittances and Nutrition Outcomes of Left-Behind Children: A National Level Quantitative Assessment of Guatemala. AB - Historically, Guatemalans have suffered high rates of poverty and malnutrition while nearly ten percent of their population resides abroad. Many Guatemalan parents use economic migration, mainly international migration to the United States, as a means to improve the human capital prospects of their children. However, as this investigation shows, the timing of migration events in relation to left-behind children's ages has important, often negative and likely permanent, repercussions on the physical development of their children. To illustrate these dynamics, this investigation uses an instrumental variables framework to disentangle the countervailing effects of Guatemalan fathers' absences due to migration from concomitant remittances on left-behind children's growth outcomes. Based on national-level data collected in 2000, the investigation reveals that the international migration of a father in the previous year is correlated with a 22.1% lower length/height-for-age z-score for the average left-behind child aged <= 3. In contrast, the receipt of remittance income has no influence on the physical stature of a child, which may indicate that migrant fathers with young children are not able to achieve economic success soon enough during their ventures abroad to fully ameliorate the harmful effects caused by their absences. PMID- 27002527 TI - Discovery and functional characterization of novel miRNAs in the marine medaka Oryzias melastigma. AB - The marine medaka Oryzias melastigma has often been used as a marine fish model to investigate the biological responses to environmental stresses and pollutants in marine environments. miRNAs are post-transcriptional regulators of many biological processes in a variety of organisms, and have been shown to be affected by environmental stresses, but the novel miRNA profile of marine medaka has not been reported. Using both genome and small RNA sequencings coupled with different bioinformatics analyses, we have discovered 58, 82, 234, and 201 unannotated miRNAs in the brain, liver, ovary and testis tissues of marine medaka, respectively. Furthermore, these novel miRNAs were found to target genes with tissue-specific roles such as neuron development and synaptic transmission in the brain, glucose and fat metabolism in the liver and steroidogenesis in the gonads. We here report, for the first time, novel miRNA profile of marine medaka, which will provide a foundation for future biomarkers and transgenerational studies for the assessment of environmental stresses and pollutions in the marine environments. In a boarder context, our data will provide novel insight into our knowledge of miRNome and miR research. PMID- 27002529 TI - Phase-Sensitive Inversion-Recovery MRI Improves Longitudinal Cortical Lesion Detection in Progressive MS. AB - Previous studies comparing phase sensitive inversion recovery (PSIR) to double inversion recovery (DIR) have demonstrated that use of PSIR improves cross sectional in vivo detection of cortical lesions (CL) in multiple sclerosis. We studied the utility of PSIR in detection/characterization of accrual of CL over time in a 1-year longitudinal study in primary progressive multiple sclerosis (PPMS) compared to DIR. PSIR and DIR images were acquired with 3T magnetic resonance imaging (MRI) in 25 patients with PPMS and 19 healthy controls at baseline, and after 1 year in 20 patients with PPMS. CL were classified as intracortical, leucocortical or juxtacortical. Lesion counts and volumes were calculated for both time points from both sequences and compared. Correlations with measures of physical and cognitive disability were determined as well as new CL counts and volumes. Compared to DIR, PSIR led to detection of a higher number of CL involving a larger proportion of patients with PPMS both cross-sectionally (p = 0.006, 88%) and longitudinally (p = 0.007, 95%), and led to the reclassification of a third of CL seen on DIR at each time point. Interestingly, PSIR was more sensitive to new CL accumulation over time compared to DIR. PSIR is a promising technique to monitor cortical damage and disease progression in patients with PPMS over a short-term follow-up. PMID- 27002530 TI - Are You Your Friends' Friend? Poor Perception of Friendship Ties Limits the Ability to Promote Behavioral Change. AB - Persuasion is at the core of norm creation, emergence of collective action, and solutions to 'tragedy of the commons' problems. In this paper, we show that the directionality of friendship ties affect the extent to which individuals can influence the behavior of each other. Moreover, we find that people are typically poor at perceiving the directionality of their friendship ties and that this can significantly limit their ability to engage in cooperative arrangements. This could lead to failures in establishing compatible norms, acting together, finding compromise solutions, and persuading others to act. We then suggest strategies to overcome this limitation by using two topological characteristics of the perceived friendship network. The findings of this paper have significant consequences for designing interventions that seek to harness social influence for collective action. PMID- 27002531 TI - Microhabitat Conditions in Wyoming's Sage-Grouse Core Areas: Effects on Nest Site Selection and Success. AB - The purpose of our study was to identify microhabitat characteristics of greater sage-grouse (Centrocercus urophasianus) nest site selection and survival to determine the quality of sage-grouse habitat in 5 regions of central and southwest Wyoming associated with Wyoming's Core Area Policy. Wyoming's Core Area Policy was enacted in 2008 to reduce human disturbance near the greatest densities of sage-grouse. Our analyses aimed to assess sage-grouse nest selection and success at multiple micro-spatial scales. We obtained microhabitat data from 928 sage-grouse nest locations and 819 random microhabitat locations from 2008 2014. Nest success was estimated from 924 nests with survival data. Sage-grouse selected nests with greater sagebrush cover and height, visual obstruction, and number of small gaps between shrubs (gap size >=0.5 m and <1.0 m), while selecting for less bare ground and rock. With the exception of more small gaps between shrubs, we did not find any differences in availability of these microhabitat characteristics between locations within and outside of Core Areas. In addition, we found little supporting evidence that sage-grouse were selecting different nest sites in Core Areas relative to areas outside of Core. The Kaplan Meier nest success estimate for a 27-day incubation period was 42.0% (95% CI: 38.4-45.9%). Risk of nest failure was negatively associated with greater rock and more medium-sized gaps between shrubs (gap size >=2.0 m and <3.0 m). Within our study areas, Wyoming's Core Areas did not have differing microhabitat quality compared to outside of Core Areas. The close proximity of our locations within and outside of Core Areas likely explained our lack of finding differences in microhabitat quality among locations within these landscapes. However, the Core Area Policy is most likely to conserve high quality habitat at larger spatial scales, which over decades may have cascading effects on microhabitat quality available between areas within and outside of Core Areas. PMID- 27002533 TI - Volubility of the human infant: Effects of parental interaction (or lack of it). AB - Although parental volubility, or amount of talk, has received considerable recent attention, infant volubility has received comparatively little attention despite its potential significance for communicative risk status and later linguistic and cognitive outcomes. Volubility of 16 typically developing infants from 2 to 11 months of age was longitudinally investigated in the present study across three social circumstances: parent talking to infant, parent not talking to infant and parent talking to interviewer while the infant was in the room. Results indicated that volubility was least in the Interview circumstance. There were no significant differences in volubility between the parent Talk and No Talk circumstances. Volubility was found to reduce with age. These results suggest that infants vocalise in a variety of circumstances, even when no one talks to or interacts with them. The presence of a stranger or perhaps overhearing adults speaking to each other, however, may significantly reduce infant volubility. PMID- 27002532 TI - Does the Microbiome Cause B27-related Acute Anterior Uveitis? AB - The microbiome is strongly implicated in a broad spectrum of immune-mediated diseases. Data support the concept that HLA molecules shape the microbiome. We provide hypotheses to reconcile how HLA-B27 might affect the microbiome and in turn predispose to acute anterior uveitis. These theories include bacterial translocation, antigenic mimicry, and dysbiosis leading to alterations in regulatory and effector T-cell subsets. Received 31 October 2015; revised 7 January 2016; accepted 8 January 2016; published online 22 March 2016. PMID- 27002535 TI - Imaging of Neuroendocrine Tumors. AB - Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies with a very variable clinical expression and progression. They present unique properties that are important to consider for radiological and nuclear imaging, such as APUD-characteristics (amine precursor uptake and dearboxylation), as well as the expression of somatostatin receptors. The most common localizations are the lungs, gastrointestinal tract and pancreas. The only curative treatment is surgery, but more than 50% present metastatic disease at the time of diagnosis. The systemic treatment includes chemotherapy and targeted agents, as well as peptide receptor radiotherapy. The diagnosis and follow-up of these tumors necessitate a large number of different imaging methods, such as CT, MRI, US, SRS and PET. Ultrasonography offers the possibility to take guided biopsies from different lesions. Somatostatin receptor scintigraphy was developed in the 1990s and nowadays presents the standard of care for NETs in most countries. The procedure offers a total body examination and a better staging of the disease. However, it has been replaced in most centers by PET/CT with 68Ga-DOTA somatostatin analogues with a superior spatial resolution and faster imaging (one stop procedure). Another tracer used for PET/CT is 18FDG, particularly for high grade tumors. Other more specific tracers are 18F-L-DOPA, 11C-L-DOPA and 11C-5 hydroxytryptophan, which have demonstrated excellent imaging results. The new targeted agents present a challenge in the evaluation procedure of treatment and, therefore, new imaging techniques and an improvement of currently available techniques are mandatory. PMID- 27002534 TI - Compartmentalization of functions and predicted miRNA regulation among contiguous regions of the nematode intestine. AB - The intestine of parasitic nematodes has proven an important target for therapies aimed at prevention and treatment of diseases caused by these pathogens in humans, animals and plants. We have developed a unique research model with the intestine of Ascaris suum, the large round worm of swine and humans, that will enhance biological research on this tissue. To expand utility of this model, we quantitatively compared expression of 15,382 coding RNAs and 277 noncoding, micro RNAs (miRNAs) among 3 contiguous regions of the adult A. suum intestine. Differentially expressed transcripts were identified among regions, with the largest number expressed at significantly higher levels in the anterior region, identifying this region as the most functionally unique compared to middle and posterior regions. We further identified 64 exon splice variants (from 47 genes) that are differentially expressed among these regions. A total of 2,063 intestinal mRNA transcripts were predicted to be targeted by intestinal miRNA, and negative correlation coefficients for miRNA:mRNA abundances predicted 22 likely influential miRNAs and 503 likely associated miRNA:mRNA pairs. A. suum intestinal miRNAs were identified that are conserved with intestinal miRNAs from C. elegans (10 mature sequences and 13 seed sequences conserved), and prospective intestinal miRNAs from the murine gastrointestinal nematode, Heligmosomoides polygyrus (5 mature and 11 seeds). Most of the conserved intestinal miRNAs were also high abundance miRNAs. The data provide the most comprehensive compilation of constitutively and differentially expressed genes along the length of the intestine for any nematode species. The information will guide prospective development of many hypotheses on nematode intestinal functions encoded by mRNAs, miRNAs and interactions between these RNA populations. PMID- 27002536 TI - Bilateral Ventral Intermediate Nucleus Thalamic Deep Brain Stimulation in Orthostatic Tremor. AB - BACKGROUND: Orthostatic tremor (OT) is characterized by high-frequency leg tremor when standing still, resulting in a sense of imbalance, with limited treatment options. Ventral intermediate (Vim) nucleus thalamic deep brain stimulation (DBS) has been reported as beneficial in a few cases. OBJECTIVE: To report clinical outcomes, lead locations, and stimulation parameters in 2 patients with severe medication-refractory OT treated with Vim DBS. METHODS: The patients underwent surface electromyography (EMG) to confirm the OT diagnosis. Outcomes were measured as change in tolerated standing time at the last follow-up. Lead locations were quantified using postoperative MRI. RESULTS: Vim DBS was well tolerated and resulted in improvement in standing time (patient 1: 50 s at baseline to 15 min 16 months after surgery; patient 2: 34 s at baseline to 4.2 min 7 months after surgery). Postoperative surface EMG for patient 1 demonstrated a delayed onset of tremor, lower-amplitude tremor, and periods of quiescence, but an unchanged tremor frequency. CONCLUSION: These cases provide further support for Vim DBS to improve standing time in severe medication-refractory OT. The location of the effective thalamic target for OT does not differ from the effective target for essential tremor. PMID- 27002537 TI - Verification of the Inactivation of Melanocytic Nevus in vitro Using a Newly Developed Portable High Hydrostatic Pressure Device. AB - High hydrostatic pressure (HHP) technology is a physical method for inactivating tissue. We reported that nevus specimens were inactivated after HHP at 200 MPa and that the inactivated nevus could be used as autologous dermis for covering skin defects. In this study, we verified the inactivation of nevus specimens using a newly developed portable HHP device which will be used in a clinical trial. Nevus tissue specimens were obtained from 5 patients (mean age 7.2 years, range 1-19). We cultured fibroblasts and nevus cells from the tissue specimens and then evaluated their inactivation after HHP at 200 MPa by confirming the attachment of the suspensions and by the live/dead staining of the suspensions, through the dissociation of the cells on chamber slides and by the live/dead staining of the remaining cells. The cells were also quantitatively evaluated by WST-8 assay. We then confirmed the inactivation of the nevus specimens after HHP using explant culture. Our results indicated that fibroblasts and nevus cells were inactivated after HHP at 200 MPa, with the exception of a small percentage of green-colored cells, which reflected the remaining activity of the cellular esterases after HHP. No cells migrated from the nevus specimens after HHP at 200 MPa. We verified the inactivation of fibroblasts and nevus cells cultured from nevus specimens, and in the nevus samples themselves after pressurization at 200 MPa using this device. This device could be used in clinical trials for giant congenital melanocytic nevi and may thus become useful in various medical fields. PMID- 27002538 TI - A theoretical physiologically based pharmacokinetic approach for modeling the fate of anthocyanins in vivo. AB - Recent studies on the pharmacokinetics of anthocyanins (ACNs) and their metabolites have uncovered evidence for hitherto unknown physiological effects affecting the fate of these compounds in vivo. In particular, it has been shown that the stomach, in addition to the small intestine, has an important role in absorption. Most studies still use a noncompartmental or one-compartmental approach to determine the pharmacokinetic parameters of ACNs, which does not represent the anatomical and physiological conditions that a compound is subject to in the organism. Thus, the objective of this study was to review the current knowledge of the different processes involved in the metabolism of ACNs once ingested and, based on this information, propose a theoretical physiologically based, multicompartmental pharmacokinetic (PBMK) model to describe their fate in vivo. This is the first study that reports a PBMK model for ACNs; the model provides a more physiologically representative approach for ANC metabolism, which could be used as a basis for experimental designs and interspecies scale-up. PMID- 27002539 TI - Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator. AB - Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 MUA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy. PMID- 27002540 TI - Application of the thermofluor PaSTRy technique for improving foot-and-mouth disease virus vaccine formulation. AB - Foot-and-mouth disease (FMD) has a major economic impact throughout the world and is a considerable threat to food security. Current FMD virus (FMDV) vaccines are made from chemically inactivated virus and need to contain intact viral capsids to maximize efficacy. FMDV exists as seven serotypes, each made up by a number of constantly evolving subtypes. A lack of immunological cross-reactivity between serotypes and between some strains within a serotype greatly complicates efforts to control FMD by vaccination. Thus, vaccines for one serotype do not afford protection against the others, and multiple-serotype-specific vaccines are required for effective control. The FMDV serotypes exhibit variation in their thermostability, and the capsids of inactivated preparations of the O, C and SAT serotypes are particularly susceptible to dissociation at elevated temperature. Methods to quantify capsid stability are currently limited, lack sensitivity and cannot accurately reflect differences in thermostability. Thus, new, more sensitive approaches to quantify capsid stability would be of great value for the production of more stable vaccines and to assess the effect of production conditions on vaccine preparations. Here we have investigated the application of a novel methodology (termed PaSTRy) that utilizes an RNA-binding fluorescent dye and a quantitative (q)PCR machine to monitor viral genome release and hence dissociation of the FMDV capsid during a slow incremental increase in temperature. PaSTRy was used to characterize capsid stability of all FMDV serotypes. Furthermore, we have used this approach to identify stabilizing factors for the most labile FMDV serotypes. PMID- 27002541 TI - Reliability of Neurobehavioral Assessments from Birth to Term Equivalent Age in Preterm and Term Born Infants. AB - : Neurobehavioral assessments provide insight into the functional integrity of the developing brain and help guide early intervention for preterm (<37 weeks' gestation) infants. In the context of shorter hospital stays, clinicians often need to assess preterm infants prior to term equivalent age. Few neurobehavioral assessments used in the preterm period have established interrater reliability. AIM: To evaluate the interrater reliability of the Hammersmith Neonatal Neurological Examination (HNNE) and the NICU Network Neurobehavioral Scale (NNNS), when used both preterm and at term (>36 weeks). METHODS: Thirty-five preterm infants and 11 term controls were recruited. Five assessors double-scored the HNNE and NNNS administered either preterm or at term. A one-way random effects, absolute, single-measures interclass correlation coefficient (ICC) was calculated to determine interrater reliability. RESULTS: Interrater reliability for the HNNE was excellent (ICC > 0.74) for optimality scores, and good (ICC 0.60 0.74) to excellent for subtotal scores, except for 'Tone Patterns' (ICC 0.54). On the NNNS, interrater reliability was predominantly excellent for all items. Interrater agreement was generally excellent at both time points. CONCLUSIONS: Overall, the HNNE and NNNS neurobehavioral assessments demonstrated mostly excellent interrater reliability when used prior to term and at term. PMID- 27002542 TI - Enhanced brain targeting efficacy of Olanzapine through solid lipid nanoparticles. AB - Olanzapine (OLZ) is a typical anti-psychotic drug, which is highly lipophilic in nature, belongs to Biopharmaceutical Classification System (BCS) class II category. Though OLZ is an effective agent in the treatment of Schizophrenia, but it exhibits poor bioavailability (57%) due to extensive first-pass metabolism resulted in high dose is required to achieve therapeutic concentration in brain. Emerging evidences are indicating that high dose administration of OLZ may cause Extrapyramidal symptoms (EPS) in the psychotic patients. Hence, the present study is designed to develop Olanzapine solid lipid (OLZ-SLNs) using minimal dose of OLZ thereby enhancing the brain efficacy as well as to reduce the side effects associated with OLZ. OLZ-SLNs have been prepared by "solvent diffusion method" using lipids, such as glyceryl monostearate (GMS), tripalmitin (TP), Tween 80, and Stearyl amine as positive charge inducer. The prepared OLZ-SLNs were subjected to particle size analysis, zeta potential, and poly dispersity index measurement by using Malvern Zetasizer. Pharmacokinetics assessments of OLZ-SLNs were carried in conscious male Wistar rats through intravenous administration. Results have shown that average particle size and zeta potential of SLNs of GMS and TP were ranged from 165.1 +/- 2.2 to 110.5 +/- 0.5 and 35.29 +/- 1.2 and 66.50 +/- 0.7 mV, respectively. Relative bioavailability of OLZ in the brain was increased up to 23-fold and clearance was decreased when OLZ-SLNs while administrated intravenously. The area under the curve (AUC) and mean residence time (MRT) of OLZ-SLNs in brain were higher than OLZ suspension. These results indicate that SLNs are a promising drug delivery for OLZ. It may be an effective tool to enhance the bioavailability of OLZ in the brain with less dose administration, which could reduce the EPS associated with OLZ. PMID- 27002543 TI - Solitonic dynamics and excitations of the nonlinear Schrodinger equation with third-order dispersion in non-Hermitian PT-symmetric potentials. AB - Solitons are of the important significant in many fields of nonlinear science such as nonlinear optics, Bose-Einstein condensates, plamas physics, biology, fluid mechanics, and etc. The stable solitons have been captured not only theoretically and experimentally in both linear and nonlinear Schrodinger (NLS) equations in the presence of non-Hermitian potentials since the concept of the parity-time -symmetry was introduced in 1998. In this paper, we present novel bright solitons of the NLS equation with third-order dispersion in some complex symmetric potentials (e.g., physically relevant -symmetric Scarff-II-like and harmonic-Gaussian potentials). We find stable nonlinear modes even if the respective linear -symmetric phases are broken. Moreover, we also use the adiabatic changes of the control parameters to excite the initial modes related to exact solitons to reach stable nonlinear modes. The elastic interactions of two solitons are exhibited in the third-order NLS equation with -symmetric potentials. Our results predict the dynamical phenomena of soliton equations in the presence of third-order dispersion and -symmetric potentials arising in nonlinear fiber optics and other physically relevant fields. PMID- 27002546 TI - Fermentable oligosaccharide, disaccharide, monosaccharide and polyol content of foods commonly consumed by ethnic minority groups in the United Kingdom. AB - Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is an effective management approach for functional bowel disorders; however, its application is limited by the paucity of food composition data available for ethnic minority groups. The aim was to identify and measure the FODMAP content of these commonly consumed foods. According to their perceived importance to clinical practise, the top 20 ranked foods underwent FODMAP analysis using validated analytical techniques (total fructans, Megazyme hexokinase (HK) assay; all others, high-performance liquid chromatography (HPLC) with evaporative light scattering detectors). Of the 20 foods analysed, five were identified as significant sources of at least one FODMAP. Fructans and galacto-oligosaccharides were the major FODMAPs in these foods, including channa dal (0.13 g/100 g; 0.36 g/100 g), fenugreek seeds (1.11 g/100 g; 1.27 g/100 g), guava (0.41 g/100 g; not detected), karela (not detected; 1.12 g/100 g) and tamarind (2.35 g/100 g; 0.02 g/100 g). Broadening the availability of FODMAP composition data will increase the cultural application of low FODMAP dietary advice. PMID- 27002548 TI - When should pregnancies that extended beyond term be induced? AB - OBJECTIVE: To compare maternal and neonatal outcomes associated with a policy for induction of labor at >= 41 versus at >=42 weeks'. STUDY DESIGN: Retrospective cohort study of a 2 years' period before and after policy change from induction of labor at >= 42 gestational weeks' versus >=41 gestational weeks. RESULTS: During the 41-policy period (N = 968), the induction rate was higher, 60% versus 40% (p < 0.0001) while the cesarean delivery (CD) rate was lower, 15% versus 19.4% (p = 0.0135). Moreover, among women that were induced, the rate of CD was lower during the 41-policy period, 19% versus 27% (p = 0.0067). No significant differences in maternal or neonatal outcomes were noted. There was one case of intrauterine fetal death at 41 + 4 weeks during the 42-policy period. CONCLUSION: As a policy for induction of labor at >= 41 reduces the rate of CD without any adverse maternal or neonatal outcomes, such a policy seems to be superior to a policy for induction at >= 42 weeks. PMID- 27002550 TI - Ambient and focal visual processing of naturalistic activity. AB - When people inspect a picture, they progress through two distinct phases of visual processing: an ambient, or exploratory, phase that emphasizes input from peripheral vision and rapid acquisition of low-frequency information, followed by a focal phase that emphasizes central vision, salient objects, and high-frequency information. Does this qualitative shift occur during dynamic scene viewing? If so, when? One possibility is that shifts to exploratory processing are triggered at subjective event boundaries. This shift would be adaptive, because event boundaries typically occur when activity features change and when activity becomes unpredictable. Here, we used a perceptual event segmentation task, in which people identified boundaries between meaningful units of activity, to test this hypothesis. In two studies, an eye tracker recorded eye movements and pupil size while participants first watched movies of actors engaged in everyday activities and then segmented them into meaningful events. Saccade amplitudes and fixation durations during the initial viewings suggest that event boundaries function much like the onset of a new picture during static picture presentation: Viewers initiate an ambient processing phase and then progress to focal viewing as the event progresses. These studies suggest that this shift in processing mode could play a role in the formation of mental representations of the current environment. PMID- 27002551 TI - Impairment of visual memory for objects in natural scenes by simulated central scotomata. AB - Because of the close link between foveal vision and the spatial deployment of attention, typically only objects that have been foveated during scene exploration may form detailed and persistent memory representations. In a recent study on patients suffering from age-related macular degeneration, however, we found surprisingly accurate visual long-term memory for objects in scenes. Normal exploration patterns that the patients had learned to rereference saccade targets to an extrafoveal retinal location. This rereferencing may allow use of an extrafoveal location as a focus of attention for efficient object encoding into long-term memory. Here, we tested this hypothesis in normal-sighted observers with gaze-contingent central scotoma simulations. As these observers were inexperienced in scene exploration with central vision loss and had not developed saccadic rereferencing, we expected deficits in long-term memory for objects. We used the same change detection task as in our patient study, probing sensitivity to object changes after a period of free scene exploration. Change detection performance was significantly reduced for two types of scotoma simulation diminishing foveal and parafoveal vision--a visible gray disc and a more subtle image warping--compared with unimpaired controls, confirming our hypothesis. The impact of a smaller scotoma covering specifically foveal vision was less distinct, leading to a marginally significant decrease of long-term memory performance compared with controls. We conclude that attentive encoding of objects is deficient when central vision is lost as long as successful saccadic rereferencing has not yet developed. PMID- 27002549 TI - Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton. AB - The unicellular cyanobacterium UCYN-A, one of the major contributors to nitrogen fixation in the open ocean, lives in symbiosis with single-celled phytoplankton. UCYN-A includes several closely related lineages whose partner fidelity, genome wide expression and time of evolutionary divergence remain to be resolved. Here we detect and distinguish UCYN-A1 and UCYN-A2 lineages in symbiosis with two distinct prymnesiophyte partners in the South Atlantic Ocean. Both symbiotic systems are lineage specific and differ in the number of UCYN-A cells involved. Our analyses infer a streamlined genome expression towards nitrogen fixation in both UCYN-A lineages. Comparative genomics reveal a strong purifying selection in UCYN-A1 and UCYN-A2 with a diversification process ~91 Myr ago, in the late Cretaceous, after the low-nutrient regime period occurred during the Jurassic. These findings suggest that UCYN-A diversified in a co-evolutionary process, wherein their prymnesiophyte partners acted as a barrier driving an allopatric speciation of extant UCYN-A lineages. PMID- 27002552 TI - Visual Functioning and Health-related Quality-of-Life are Compromised in Patients with Uveitis. AB - PURPOSE: To assess the vision-related (VR) and health-related (HR) quality-of life (QoL) of patients with uveitis. METHODS: In total, 60 patients with uveitis, 81 patients with diabetic retinopathy (DR), and 70 healthy subjects completed the National Eye Institute Visual Functioning Questionnaire and the Medical Outcome Study 36-Item Short Form. RESULTS: Patients with uveitis reported lower HR- and VR-QoL than healthy subjects (p<0.05) and lower VR-QoL (p<0.001) than patients with DR. For patients with uveitis, multiple linear regression analyses indicated that lower HR-QoL scores were predicted by younger age (p<0.01), while lower VR QoL scores were predicted by poorer visual acuity (p<0.001), ocular comorbidities (p<0.05), and female sex (p<0.05). CONCLUSIONS: Patients with uveitis have significantly poorer VR- and HR-QoL than healthy control subjects. Uveitis has a more debilitating impact on VR-QoL than DR. PMID- 27002553 TI - Severe alcohol withdrawal syndrome: Evolution of care and impact of adjunctive therapy on course and complications of 171 intensive care unit patients. AB - This single site retrospective observational study assessed the evolution of sedation therapy for severe alcohol withdrawal syndrome in the intensive care unit. Patient records for 2 intervals were reviewed: Interval 1, which included 87 intensive care unit patients admitted January 2005 through September 2007, for whom benzodiazedpine monotherapy was utilized; and Interval 2, January 2010 through December 2010, for whom 54 of 84 (64.3%) intensive care unit patients, including all those intubated, received adjunctive agents, including dexmedetomidine or propofol. Clinical management was similar for both intervals, as well as prevalence of alcohol withdrawal syndrome versus total adult hospital admissions and comorbid conditions. Overall, respiratory failure (53 versus 39%), seizures (36 versus 18%), and pneumonia (51 versus 38%) were less frequent during Interval 2 (all p < .05), with lower benzodiazedpine basal dose requirements for those given adjunctive therapy. However, if instances of pneumonia or respiratory failure related to seizures prior to intensive care unit admission are excluded, the prevalence of these complications was similar (p = ns) for Interval 1 and Interval 2. Intensive care unit and hospital length of stay were not altered by adjunctive therapy, which was typically employed for more severely affected patients. High intensity sedation with adjunctive drugs led to few cardiovascular adverse events and may have facilitated management, but did not alter intensive care unit course of severe alcohol withdrawal syndrome. PMID- 27002554 TI - Real-Time Visualization of Left Lung Consolidation Relief Using Lung Ultrasound. PMID- 27002558 TI - Review of ultrasound image guidance in external beam radiotherapy part II: intra fraction motion management and novel applications. AB - Imaging has become an essential tool in modern radiotherapy (RT), being used to plan dose delivery prior to treatment and verify target position before and during treatment. Ultrasound (US) imaging is cost-effective in providing excellent contrast at high resolution for depicting soft tissue targets apart from those shielded by the lungs or cranium. As a result, it is increasingly used in RT setup verification for the measurement of inter-fraction motion, the subject of Part I of this review (Fontanarosa et al 2015 Phys. Med. Biol. 60 R77 114). The combination of rapid imaging and zero ionising radiation dose makes US highly suitable for estimating intra-fraction motion. The current paper (Part II of the review) covers this topic. The basic technology for US motion estimation, and its current clinical application to the prostate, is described here, along with recent developments in robust motion-estimation algorithms, and three dimensional (3D) imaging. Together, these are likely to drive an increase in the number of future clinical studies and the range of cancer sites in which US motion management is applied. Also reviewed are selections of existing and proposed novel applications of US imaging to RT. These are driven by exciting developments in structural, functional and molecular US imaging and analytical techniques such as backscatter tissue analysis, elastography, photoacoustography, contrast-specific imaging, dynamic contrast analysis, microvascular and super resolution imaging, and targeted microbubbles. Such techniques show promise for predicting and measuring the outcome of RT, quantifying normal tissue toxicity, improving tumour definition and defining a biological target volume that describes radiation sensitive regions of the tumour. US offers easy, low cost and efficient integration of these techniques into the RT workflow. US contrast technology also has potential to be used actively to assist RT by manipulating the tumour cell environment and by improving the delivery of radiosensitising agents. Finally, US imaging offers various ways to measure dose in 3D. If technical problems can be overcome, these hold potential for wide-dissemination of cost-effective pre-treatment dose verification and in vivo dose monitoring methods. It is concluded that US imaging could eventually contribute to all aspects of the RT workflow. PMID- 27002559 TI - Closed Incision Negative-Pressure Therapy Is Associated with Decreased Surgical Site Infections: A Meta-Analysis. PMID- 27002560 TI - Is Double-Blinded Peer Review Necessary? The Effect of Blinding on Review Quality. PMID- 27002561 TI - Reconstruction of Large Abdominal Wall Defects Using Neurotized Vascular Composite Allografts. PMID- 27002562 TI - Implications of Rheumatic Disease and Biological Response-Modifying Agents in Plastic Surgery. PMID- 27002563 TI - Reply: Reconstruction of Large Abdominal Wall Defects Using Neurotized Vascular Composite Allografts. PMID- 27002564 TI - Development of cross-priming amplification for direct detection of the African Swine Fever Virus, in pig and wild boar blood and sera samples. AB - African swine fever (ASF) is considered a major threat to the production of pigs worldwide. The ASF aetiological agent, ASFV, is the sole member of the Asfivirus genus, belonging to the Asfarviridae family. An effective ASF vaccine is not currently available, thus the only measures of ASF spread control include, reliable and fast diagnosis. Officially approved, diagnostic methods include, virus isolation, serological assays, including enzyme-linked immunosorbent assay and immunoperoxidase assay (IPT) and different modifications of the polymerase chain reaction (PCR). This paper describes the first development and application of a cross-priming amplification method (CPA) for the direct detection of genetic ASFV material, in blood and sera from pigs and wild boars. This method is specific only to ASFV DNA. The study showed that CPA had equal sensitivity, in comparison to the official, universal probe library (UPL) real-time PCR and reached 7.2 copies of standard plasmid DNA, containing a p72 gene fragment. This method was capable of detecting ASFV DNA in all examined blood samples, originating from pigs; n = 10 and wild boars; n = 76. The obtained results were also confirmed by the officially approved, real-time PCR. The developed CPA might be further used by local and county veterinary officers, hunters or pig farmers, for preliminary ASF diagnosis. SIGNIFICANCE AND IMPACT OF THE STUDY: The spread of the African swine fever virus (ASFV) among infected pigs and wild boars, is currently one of the most important facets of virus transmission in eastern Europe. Cross-priming amplification (CPA) has been developed, for fast and direct development of genetic ASFV material in the blood and sera of infected pigs and wild boars. It has been shown that CPA is a rapid, sensitive and specific isothermal method for the detection of ASFV DNA, in directly collected blood or sera from pigs and wild boars. PMID- 27002565 TI - Characteristics and outcome of patients presenting to the emergency department after autologous/allogeneic stem cell transplantation. AB - INTRODUCTION: Hematopoietic stem cell transplantations are still associated with a high risk of complications. Here, we characterize patients after autologous or allogeneic transplantation presenting to the emergency department and investigate factors associated with patients' outcome after hospitalization. METHODS: Patients who had previously undergone autologous or allogeneic stem cell transplantation were included in this study and data were collected retrospectively. We analyzed patients' characteristics and outcome, and identified factors associated with outcome. RESULTS: A total of 35% of presenting autologous and 52% of allogeneic patients were hospitalized for more than 7 days. In-hospital mortality was 4% (autologous) and 11% (allogeneic patients). In patients with a history of autologous transplantation, multivariate analysis indicated radiologic signs of pneumonia as an independent factor associated with the endpoint 'hospitalization of more than 7 days' (P<0.001). Furthermore, in multivariate analysis, C-reactive protein levels greater than 5 mg/l (P=0.006), low hemoglobin (P=0.002), and radiologic signs of pneumonia (P=0.004) were associated independently with an increase in the endpoint 'total duration of hospitalization'. In patients with a history of allogeneic transplantation, multivariate analysis indicated radiologic signs of pneumonia (P<0.001) and graft versus-host-disease (P=0.006) to be associated independently with the endpoint 'hospitalization of more than 7 days'. Furthermore, radiologic signs of pneumonia were associated independently with the endpoints 'ICU treatment' (P<0.001), the 'total duration of hospitalization' (P<0.001), and 'in-hospital mortality' (P=0.002). A low platelet count was associated independently with an increase in the endpoint 'duration of hospitalization' (P=0.001). CONCLUSION: Radiologic signs of pneumonia were associated independently with worse clinical outcomes including hospitalization, the need for ICU treatment, and death. PMID- 27002566 TI - The Abbreviated Mental Test 4 for cognitive screening of older adults presenting to the Emergency Department. AB - OBJECTIVES: A commonly cited reason for the infrequent detection of cognitive impairment in the Emergency Department (ED) is the lack of an appropriate screening tool. The Abbreviated Mental Test 4 (AMT4) is a brief instrument recommended for cognitive screening of older adults in the ED. However, its exact utility in the detection of altered mental status in the ED is yet to be fully determined. METHODS: The present study evaluated the ability of the AMT4 to identify impaired mental status in the ED, defined as positive scores on either the Confusion Assessment Method-ICU for delirium, the standardized Mini Mental State Examination as a general cognitive screener or the Eight-item Interview to Differentiate Aging and Dementia for dementia. RESULTS: Of 196 adults at least 70 years of age (mean: 78.5+/-5.9), the AMT4 had a sensitivity of 0.53 (0.42-0.63) and a specificity of 0.96 (0.89-0.99) for impaired mental status in the ED. The AMT4 was positive in almost all patients (92%; 24/26) screening positive for delirium, but less than half (47.8%; 22/46) of those screening positive for probable dementia, and less than a quarter (22.2%; 6/27) of those screening positive for probable cognitive impairment. CONCLUSION: The present study found that the limited sensitivity of the AMT4 in identifying the majority of cognitively impaired persons restricts its use in isolation as a general cognitive screener in the ED. PMID- 27002567 TI - The need to improve reporting of routinely collected dermatology data for patient benefit. PMID- 27002568 TI - Ingenol mebutate for actinic keratosis: a field-directed therapy with short duration. PMID- 27002569 TI - Skin autofluorescence in dermatology - is photography an option? PMID- 27002570 TI - Hidradenitis suppurativa, neutrophilic dermatoses and autoinflammation: what's the link? PMID- 27002571 TI - Diagnosing dermatophytic infections in the molecular age. PMID- 27002572 TI - Beyond the tip of the iceberg: the role of phosphoinositide 3-kinase/AKT in acne inversa/hidradenitis suppurativa. PMID- 27002573 TI - Psoriasis, extradomain A+ fibronectin and the extracellular matrix. PMID- 27002574 TI - Plasma will.... PMID- 27002575 TI - Diverse methodologies for assessing photoaged skin. PMID- 27002576 TI - Evaluating the genotypes and neuropsychiatric phenotypes in Darier disease. PMID- 27002577 TI - Using dermoscopy to detect tinea of vellus hair. PMID- 27002578 TI - Cover Image: A dashed hair. PMID- 27002580 TI - Image Gallery: Linear unilateral basaloid follicular hamartoma: a unique presentation. PMID- 27002585 TI - Conflict of Interest Disclosures. PMID- 27002581 TI - Image Gallery: Xeroderma pigmentosum. PMID- 27002587 TI - Dopamine Surface Modification of Trititanate Nanotubes: Proposed In-Situ Structure Models. AB - Two models for self-assembled dopamine on the surface of trititanate nanotubes are proposed: individual monomer units linked by pi-pi stacking of the aromatic regions and mono-attached units interacting through hydrogen bonds. This was investigated with solid state NMR spectroscopy studies and powder X-ray diffraction. PMID- 27002588 TI - Factors Associated With Full Implementation of Scope of Practice. AB - PURPOSE: To describe whether nurses fully implement their scope of practice; nurses' perceptions of future practice implementation; and the association between scope of practice implementation with professional autonomy and self efficacy. DESIGN: A descriptive correlational study was conducted using a convenience sample of 145 registered nurses with post-basic certification from two Israeli university hospitals, from May 2012 to September 2013. METHODS: Five questionnaires were distributed: (a) Demographic and Work Characteristics, (b) Implementation of Scope of Practice, (c) Attitudes Towards Future Practice, (d) Practice Behavior Scale, and (e) Practice Self-Efficacy. Descriptive statistics for all demographic and questionnaire data were analyzed. Two regression models were developed, where current and future implementations were the criterion variables and demographic and work characteristics, professional autonomy, and self-efficacy were the predictors. FINDINGS: High levels of professional autonomy, self-efficacy, and attitudes towards future practice were found in contrast to low or moderate levels of current implementation of the full extent of scope of practice. Primary reasons associated with low implementation were lack of relevance to practice and permission to perform the practice. Significant associations were found between professional autonomy, self-efficacy, and attitudes towards future practice, but not with current implementation. CONCLUSIONS: Nurses wanted to practice to the full extent of their scope of practice and felt able to do so but were hindered by administrative and not personal barriers. CLINICAL RELEVANCE: Even though staff nurses with post-basic certification had high levels of professional autonomy and self-efficacy, many were not implementing the full extent of their scope of practice. Similar to findings from around the world, external factors, such as administrative and policy barriers, were found to thwart the full implementation of nurses' full scope of practice. Therefore, practicing nurses should be aware of these barriers and work towards reducing them. PMID- 27002589 TI - Distally based subcutaneous veins for venous insufficiency of the reverse posterior interosseous artery flap. AB - BACKGROUND: The reverse posterior interosseous artery flap (PIAF) provides soft, thin, and pliable tissue for upper extremity reconstruction without sacrificing any major arteries of the hand. The authors performed a new technique that included one extra distally based subcutaneous vein within the pedicle to diminish venous insufficiency and they aimed to present the results of reconstruction with this technique. PATIENTS AND METHODS: Twelve patients with a mean age of 30 years (range 5-52 years) underwent reverse PIAF surgery. The defects were located on the hand and wrist, with a mean area of 57.8 cm2 (range 20-99 cm2) . After the skin between the distal edge and the pivot point of the flap was elevated, the most reliable subcutaneous vein was chosen, chased, and included within the flap. RESULTS: The average size of the PIAF was 6 * 5 cm to 12 * 9 cm (mean area: 64.4 cm2 ) and the median follow-up time was 13 months (range 4-16 months). The mean quick Disabilities of the Arm, Shoulder and Hand (DASH) score was 21.4, indicating a low degree of disability. Of the 12 patients, ten were very satisfied and two were satisfied with the result of the reconstruction. All but one flap survived completely. One flap was nearly totally lost due to arterial insufficiency after hemodialysis. We observed no venous congestion or insufficiency in the patients. CONCLUSIONS: Subcutaneous veins may be reliable and useful for overcoming major drawbacks associated with reverse flow posterior interosseous artery flap and for diminishing flap loss due to venous insufficiency. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:384-390, 2016. PMID- 27002590 TI - Fiber-Shaped Perovskite Solar Cells with High Power Conversion Efficiency. AB - A perovskite solar cell fiber is created with a high power conversion efficiency of 7.1% through a controllable deposition method. A combination of aligned TiO2 nanotubes, a uniform perovskite layer, and transparent aligned carbon nanotube sheet contributes to the high photovoltaic performance. It is flexible and stable, and can be woven into smart clothes for wearable applications. PMID- 27002591 TI - Effect of polaprezinc on oral mucositis, irradiation period, and time to discharge in patients with head and neck cancer. AB - BACKGROUND: The purpose of the present study was to determine whether polaprezinc suspension in sodium alginate (P-AG) reduces the irradiation period and time to discharge after completion of radiotherapy in patients with head and neck cancer. METHODS: The incidence and severity of oral mucositis, the irradiation period, and the time to discharge in patients who received radiotherapy with head and neck cancer were investigated retrospectively from the medical records. RESULTS: The incidence of grade 3 oral mucositis was significantly lower in the P-AG group than in the control group (16.5% vs 52.0%; p = .0003). P-AG also significantly reduced median duration of radiotherapy (hazard ratio [HR] = 0.557; 95% confidence interval [CI] = 0.357-0.871; p = .0149) and median time to discharge after completion of radiotherapy (HR = 0.604; 95% CI = 0.386-0.946; p = .028). CONCLUSION: P-AG reduced the irradiation period and the time to discharge after completion of radiotherapy by preventing oral mucositis in patients with head and neck cancer. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1387-1392, 2016. PMID- 27002592 TI - Demographic responses to weather fluctuations are context dependent in a long lived amphibian. AB - Weather fluctuations have been demonstrated to affect demographic traits in many species. In long-lived organisms, their impact on adult survival might be buffered by the evolution of traits that reduce variation in interannual adult survival. For example, skipping breeding is an effective behavioral mechanism that may limit yearly variation in adult survival when harsh weather conditions occur; however, this in turn would likely lead to strong variation in recruitment. Yet, only a few studies to date have examined the impact of weather variation on survival, recruitment and breeding probability simultaneously in different populations of the same species. To fill this gap, we studied the impact of spring temperatures and spring rainfall on survival, on reproductive skipping behavior and on recruitment in five populations of a long-lived amphibian, the yellow-bellied toad (Bombina variegata). Based on capture recapture data, our findings demonstrate that survival depends on interactions between age, population and weather variation. Varying weather conditions in the spring result in strong variation in the survival of immature toads, whereas they have little effect on adult toads. Breeding probability depends on both the individual's previous reproductive status and on the weather conditions during the current breeding season, leading to high interannual variation in recruitment. Crucially, we found that the impact of weather variation on demographic traits is largely context dependent and may thus differ sharply between populations. Our results suggest that studies predicting the impact of climate change on population dynamics should be taken with caution when the relationship between climate and demographic traits is established using only one population or few populations. We therefore highly recommend further research that includes surveys replicated in a substantial number of populations to account for context-dependent variation in demographic processes. PMID- 27002593 TI - Molecular Architectonics of Naphthalenediimides for Efficient Structure-Property Correlation. AB - We present a bioinspired design strategy to effectively tailor the assembly of naphthalenediimides (NDIs) into a wide variety of architectures by functionalizing with amino acid derivatives. This bioinspired process of custom designing and engineering molecular assemblies is termed "bioinspired architectonics". By employing minute structural mutations in the form of alpha substituents of amino acids, we successfully engineered molecular assembly of NDIs into zero-dimensional (0D, spheres), one-dimensional (1D, fibers), and two dimensional (2D, sheets) architectures. The 2D sheets of phenylalanine methylester appended NDI 1 showed remarkable bulk electron mobility of up to 1 cm(2) V(-1)s(-1). With the aid of photophysical, diffraction, and microscopy techniques we rationalize the effect of molecular structure with their ordering and electronic properties in an effort to find structure-property correlations via a bioinspired modular approach. PMID- 27002594 TI - Highly Stable and Conductive Microcapsules for Enhancement of Joule Heating Performance. AB - Nanocarbons show great promise for establishing the next generation of Joule heating systems, but suffer from the limited maximum temperature due to precociously convective heat dissipation from electrothermal system to surrounding environment. Here we introduce a strategy to eliminate such convective heat transfer by inserting highly stable and conductive microcapsules into the electrothermal structures. The microcapsule is composed of encapsulated long-chain alkanes and graphene oxide/carbon nanotube hybrids as core and shell material, respectively. Multiform carbon nanotubes in the microspheres stabilize the capsule shell to resist volume-change-induced rupture during repeated heating/cooling process, and meanwhile enhance the thermal conductance of encapsulated alkanes which facilitates an expeditious heat exchange. The resulting microcapsules can be homogeneously incorporated in the nanocarbon-based electrothermal structures. At a dopant of 5%, the working temperature can be enhanced by 30% even at a low voltage and moderate temperature, which indicates a great value in daily household applications. Therefore, the stable and conductive microcapsule may serve as a versatile and valuable dopant for varieties of heat generation systems. PMID- 27002596 TI - Single Hydrogen Bond Donation from Flavin N5 to Proximal Asparagine Ensures FAD Reduction in DNA Photolyase. AB - The spread of the absorbance of the stable FADH(*) radical (300-700 nm) allows CPD photolyase to highly efficiently form FADH(-), making it functional for DNA repair. In this study, FTIR spectroscopy detected a strong hydrogen bond, from FAD N5-H to the carbonyl group of the Asn378 side chain, that is modulated by the redox state of FAD. The observed characteristic frequency shifts were reproduced in quantum-mechanical models of the flavin binding site, which were then employed to elucidate redox tuning governed by Asn378. We demonstrate that enhanced hydrogen bonding of the Asn378 side chain with the FADH(*) radical increases thermodynamic stabilization of the radical state, and further ensures kinetic stabilization and accumulation of the fully reduced FADH(-) state. PMID- 27002597 TI - Combined Theoretical and in Situ Scattering Strategies for Optimized Discovery and Recovery of High-Pressure Phases: A Case Study of the GaN-Nb2O5 System. AB - The application of pressure in solid-state synthesis provides a route for the creation of new and exciting materials. However, the onerous nature of high pressure techniques limits their utility in materials discovery. The systematic search for novel oxynitrides-semiconductors for photocatalytic overall water splitting-is a representative case where quench high-pressure synthesis is useful and necessary in order to obtain target compounds. We utilize state of the art crystal structure prediction theory (USPEX) and in situ synchrotron-based X-ray scattering to speed up the discovery and optimization of novel compounds using high-pressure synthesis. Using this approach, two novel oxynitride phases were discovered in the GaN-Nb2O5 system. The (Nb2O5)0.84:(NbO2)0.32:(GaN)0.82 rutile structured phase was formed at 1 GPa and 900 degrees C and gradually transformed to a alpha-PbO2-related structure above 2.8 GPa and 1000 degrees C. The low pressure rutile type phase was found to have a direct optical band gap of 0.84 eV and an indirect gap of 0.51 eV. PMID- 27002598 TI - Peak fat oxidation during self-paced activities of daily life: influence of sex and body composition. AB - BACKGROUND: Increasing physical activity is a cornerstone in the treatment of overweight individuals and self-selected exercise intensity leads to higher adherence to physical activity. However, information on differences in energy expenditure and fat oxidation between sexes regarding common self-paced activities of daily living are rare. METHODS: We divided 33 subjects into normal weight (NW, N.=21) and overweight (OW, N.=12). Energy expenditure and substrate oxidation was measured during six self-paced physical activities of daily living using a portable spirometric system. We also determined maximum aerobic capacity (VO2max) and estimated free-living physical activity with a multi-sensor device. RESULTS: For all six activities, total energy expenditure was not different between NW and OW subjects in both sexes. The peak fat oxidation during physical activities was reached at higher intensities for women (NW 57+/-15%; OW 53+/-8% of VO2max) compared to men (NW 41+/-8%; OW 42+/-9% of VO2max) with no differences between NW and OW subjects. The majority of OW (92%) but not NW (42%) subjects reached their highest fat oxidation during walking. The self-selected walking speed was not significantly different between NW and OW men (NW 5.25+/-0.48 km/h, OW 5.52+/-0.42 km/h) and NW and OW women (NW 5.16+/-0.89 km/h, OW 5.01+/-0.42 km/h). CONCLUSIONS: When physical activity aims to maximizing fat oxidation, women should exercise at higher relative intensities than men, regardless of being normal weight or overweight. Self-paced walking is a suitable activity for overweight subjects to achieve high rates of both total energy expenditure and fat oxidation. PMID- 27002599 TI - Tales of mystery and imagination in stable isotope geochemistry: celebrating the 75th birthday of Jochen Hoefs. AB - We celebrate the contribution of Jochen Hoefs to the development of stable isotope (bio)geochemistry on the occasion of his 75th birthday. PMID- 27002600 TI - Oxygen isotope composition of North American bobcat (Lynx rufus) and puma (Puma concolor) bone phosphate: implications for provenance and climate reconstruction. AB - Feline carnivores are threatened by illegal wildlife trade. Tracing the provenance of unknown felid tissues via stable isotope analysis could provide important information in wildlife crime investigations. The oxygen isotope composition of mammalian skeletal phosphate (delta(18)Op) is widely applied to trace the origin of animal remains and to reconstruct migratory patterns in palaeontological, archaeological, ecological and wildlife forensic applications. Teeth and bones of terrestrial mammals form at constant body temperature in isotope equilibrium with body water, which is predominantly controlled by ingested meteoric water (delta(18)Ow) that varies systematically with latitude, altitude and climate. Here we analysed delta(18)Op of 106 North American puma and bobcat bones of known geographic origin to establish the first delta(18)Op delta(18)Ow regression for feline carnivores: delta(18)Op = 0.40(+/-0.04) * delta(18)Ow + 20.10(+/-0.40) (R(2) = 0.46, n = 106). This was compared with those from their respective prey species (deer and rabbit), a canid carnivore (fox) and other placental mammals. Effects of species, sex and relative humidity on the feline delta(18)Op-delta(18)Ow correlation were analysed and additional intra individual tissue comparisons (hair delta(18)Oh vs. bone delta(18)Op) were performed for some bobcat individuals. Bobcats and pumas exhibited only a moderate delta(18)Op-delta(18)Ow correlation, which differed from canid carnivores and other placental mammals. However, feline delta(18)Op values revealed a moderate relation with delta(18)Ow, which lacks for the delta(18)Oh of hair from the same bobcat individuals. This indicates a difference in oxygen isotope routing from body water to bioapatite and hair. Most herbivores and omnivores track delta(18)Ow in their bioapatite delta(18)Op values much better, whereas delta(18)Op and especially delta(18)Oh values of feline carnivores are less precise proxies for meteoric water delta(18)Ow values and thus for provenance determination in wildlife forensics and palaeoclimate reconstructions. Oxygen isotope fingerprinting of bobcat and puma is biased by factors related to their diet, behaviour and metabolism that need to be better understood. PMID- 27002601 TI - Visible-Light-Induced Direct Thiolation at alpha-C(sp(3))-H of Ethers with Disulfides Using Acridine Red as Photocatalyst. AB - A simple and efficient method for the preparation of alpha-arylthioethers through a visible-light-induced direct thiolation at alpha-C(sp(3))-H of ethers with diaryl disulfides was developed using acridine red as a novel photocatalyst. The reactions occurred at ambient conditions and generated the corresponding products in good to excellent yields, ignoring steric effect of disulfides. PMID- 27002602 TI - Enantioselective endocrine disrupting effects of omeprazole studied in the H295R cell assay and by molecular modeling. AB - Enantiomers possess different pharmacokinetic and pharmacodynamic properties and this may not only influence the therapeutic effect of a drug but also its toxicological effects. In the present work we investigated the potential enantioselective endocrine disrupting effects of omeprazole (OME) and its two enantiomers on the human steroidogenesis using the H295R cell line. Differences in production of 16 steroid hormones were analyzed using LC-MS/MS. Additionally, to evaluate the differences in binding modes of these enantiomers, docking and molecular dynamics (MD) simulations of S-omeprazole (S-OME) and R-omeprazole (R OME) in CYP17A1, CYP19A1 and CYP21A2 were carried out. Exposing H295R cells to OME and its enantiomers resulted in an increase of progesterone (PRO) and 17alpha hydroxy-progesterone (OH-PRO) levels. At the same time, a decrease in the corticosteroid and androgen synthesis was observed, indicating inhibition of CYP21A2 and CYP17A1. In both cases, the effect of R-OME was smaller compared to that of the S-OME and a certain degree of enantioselectivity of CYP17A1 and CYP21A2 was suggested. Docking indicated that the N-containing rings of OME possibly could interact with the iron atom of the heme for S-OME in CYP17A1 and S and R-OME in CYP21A2. However, density functional theory calculations suggest that the direct N-Fe interaction is weak. The study demonstrates enantioselective differences in the endocrine disrupting potential of chiral drugs such as omeprazole. These findings may have potential implications for drug safety and drug design. PMID- 27002603 TI - Emergency Contraception: Two Steps Forward, One Step Back. AB - Emergency contraceptives can prevent pregnancy, when used after unprotected sex around the time of ovulation. In the past 15 years, access to emergency contraception (EC) in the United States has increased and more women use it. Emerging data may tailor EC prescribing based on patient weight and starting other contraception. There are several EC options-oral levonorgestrel and oral ulipristal acetate and the copper intrauterine device. Ideally, women should have EC access at low or no cost. Yet, several barriers-limited patient and provider knowledge about EC, cost, EC stocking practices, and state and federal laws exempting providers from supplying EC-make it difficult to integrate this time sensitive treatment into women's reproductive health care. PMID- 27002604 TI - Particle-Stabilized Powdered Water-in-Oil Emulsions. AB - The preparation of powdered water-in-oil (w/o) emulsions by gentle aeration of w/o emulsions stabilized by hydrophobic fumed silica particles in the presence of oleophobic fluorinated clay particles is reported for an alkane and a triglyceride oil. The resultant powders consist of water drops dispersed in oil globules themselves dispersed in air (w/o/a). They contain ~80 wt % of the precursor w/o emulsion and were stable to phase separation for over 1 year but release oil and water when sheared on a substrate. Above a certain ratio of w/o emulsion:fluorinated clay particles, the powdered emulsions partially invert to an emulsion paste, composed of air bubbles and water droplets dispersed in oil. The tap density and angle of repose of the powdered emulsions were measured and compared with those of the corresponding powdered oils making up the continuous phase of the precursor emulsions. The contact angles of water droplets under oil on glass slides spin coated with silica particles and oil drops and w/o emulsion droplets in air on compressed disks of fluorinated clay particles are consistent with the stabilization of w/o emulsions and powdered emulsions, respectively. PMID- 27002605 TI - Synthesis, characterization of alpha-amino acid Schiff base derived Ru/Pt complexes: Induces cytotoxicity in HepG2 cell via protein binding and ROS generation. AB - We have synthesized two new complexes of platinum (1) and ruthenium (2) with alpha-amino acid, l-alanine, and 2,3-dihydroxybenzaldehyde derived Schiff base (L). The ligand and both complexes were characterized by using elemental analysis and several other spectroscopic techniques viz; IR, (1)H, (13)C NMR, EPR, and ESI MS. Furthermore, the protein-binding ability of synthesized complexes was monitored by UV-visible, fluorescence and circular dichroism techniques with a model protein, human serum albumin (HSA). Both the PtL2 and RuL2 complexes displayed significant binding towards HSA. Also, in vitro cytotoxicity assay for both complexes was carried out on human hepatocellular carcinoma cancer (HepG2) cell line. The results showed concentration-dependent inhibition of cell viability. Moreover, the generation of reactive oxygen species was also evaluated, and results exhibited substantial role in cytotoxicity. PMID- 27002607 TI - Success of transdisciplinary science requires monodisciplinary support. PMID- 27002606 TI - Effect of IFN-gamma, IL-12 and IL-10 cytokine production and mRNA expression in tuberculosis patients with diabetes mellitus and their household contacts. AB - OBJECTIVE: The study was carried out to understand the influence of IFN-gamma, IL 12 and IL-10 cytokine production and expression in tuberculosis patients with diabetes mellitus (TBDM) and their household contacts (HHC). METHODOLOGY: The study involved a total of 300 subjects, 50 in each category of TBDM, TBDM HHC, pulmonary tuberculosis patients (PTB), PTB HHC, DM and healthy controls (HC). TBDM, PTB and their HHC, 25 each were followed at different intervals to determine their immune responses in Ag85A stimulated culture supernatants by Enzyme Linked Immunosorbent Assay (ELISA). mRNA expression by TRIZOL method in 5 cases of each category and follow-up studies were performed. RESULTS: IFN-gamma and IL-12 cytokine production markedly decreased and that of IL-10 increased after Ag85A M.tb stimulation, however anti TB treatment reconstituted the response in TBDM and PTB patients. The household contacts revealed cytokine gene expression similar to that of patients and two of them developed the disease during follow-up. CONCLUSION: Cytokine responses of the patients retained after treatment highlighting the antigen importance, hence further studies with recombinant cytokines may help in coming up with a biomarker. Analogous immune responses of household contacts with the TBDM and PTB patients may assist in recognizing the high risk individuals. PMID- 27002608 TI - Hepatitis B virus genotype A: design of reference sequences for sub-genotypes. AB - Genotype A of hepatitis B virus (HBV/A) is widespread and is currently divided into six sub-genotypes. Suitable reference sequences for different sub-genotypes can facilitate research on HBV/A. However, the current reference sequences for this virus are insufficient. In the present work, we retrieved 442 full-length HBV/A genomic sequences from the GenBank database and classified them into sub genotypes by phylogenetic analysis. By the maximum likelihood method using the MEGA6.0 software, we established the reference sequences for different HBV/A sub genotypes. Our analyses demonstrated that these reference sequences clustered phylogenetically with known strains, indicating that the reference sequences we established indeed belonged to the right sub-genotypes. HBV/A subtype sequences were selected by geographic origins and grouped as sub-genotypes including A1 South Africa, A2-Europe, A3-Cameroon, and A5-Haiti. Reference sequences of sub genotypes A1, A2, A3, and A5 were constructed and deposited into GenBank (KP234050-KP234053). By applying phylogenetic analyses, we further determined the time to most recent common ancestor of HBV/A lineages. In conclusion, these newly established reference sequences can provide suitable reference standards for studies on the molecular biology and virology of HBV genotype A. PMID- 27002609 TI - Fast detection of coliform bacteria by means of gas chromatography-differential mobility spectrometry. AB - In this study, we demonstrate that the combination of an enzymatic method (based on Colilert-18 medium) and gas chromatography-differential mobility spectrometry (GC-DMS) can reduce the time required for detection of coliform bacteria (including Escherichia coli) from 18 to 2.5 h. The presented method includes the incubation (~2.5 h) of the sample containing coliform bacteria in Colilert-18 medium. The incubation time of 2.5 h is required for the activation of the beta galactosidase enzyme. Produced during the incubation biomarker o-nitrophenol (ONP) can be detected by means of GC-DMS within just 200 s. The detection limit for ONP was 45 ng (on-column). The method developed in this work provides significantly shorter analysis time compared with standard methods, and can be potentially adapted to the field conditions. Therefore, this method is a promising tool for an early detection of coliform bacteria (including E. coli). Graphical Abstract Fast detection of coliform bacteria by means of GC-DMS. PMID- 27002610 TI - A toxin-free enzyme-linked immunosorbent assay for the analysis of aflatoxins based on a VHH surrogate standard. AB - A toxin-free enzyme-linked immunosorbent assay (ELISA) for aflatoxins was developed using an anti-idiotype nanobody VHH 2-5 as surrogate standard. Anti idiotype nanobody VHH 2-5 was generated by immunizing an alpaca with anti aflatoxin monoclonal antibody 1C11. This assay was used to detect aflatoxins in agro-products after a simple extraction with 75 % methanol/H2O. Aflatoxin concentration was calculated by a two-step approach: the concentration of VHH 2-5 was first obtained by a four-parameter logistic regression from the detected absorbance value at 450 nm, and then converted to aflatoxin concentration by a linear equation. The assay exhibits a limit of detection (LOD) of 0.015 ng mL( 1), which is better than or comparable with conventional immunoassays. The performance of our VHH surrogate-based ELISA was further validated with a high performance liquid chromatography (HPLC) method for total aflatoxins determination in 20 naturally contaminated peanut samples, displaying a good correlation (R (2) = 0.988). In conclusion, the proposed assay represents a first example applying an anti-idiotype VHH antibody as a standard surrogate in ELISA. With the advantages of high stability and ease of production, the VHH antibody based standard surrogate can be extended in the future to immunoassays for other highly toxic compounds. Graphical Abstract ?. PMID- 27002611 TI - Fast analysis of caffeine in beverages and drugs by paper spray tandem mass spectrometry. AB - A simple and fast method based on paper spray mass spectrometry for the determination of caffeine in commercial beverages and drugs has been developed; the analyses were carried out in MRM mode, monitoring the transitions m/z 195 -> m/z 138 for caffeine and m/z 198 -> m/z 140 for the labeled internal standard. To verify the reliability of the proposed approach, a spiked sample (soda drink and paracetamol tablet) with a known amount of caffeine has been prepared and analyzed by PS-MS, providing accuracy values about 100 %; the LOQ and LOD values were calculated at 1.2 and 1.6 MUg/mL, respectively. Both beverages and drugs were also analyzed with the classic analytical method based on LC-UV measurements, showing consistent results between the two approaches, thus confirming the reliability of the developed ambient MS determination. Graphical Abstract The assay of caffeine by paper mass spectrometry. PMID- 27002612 TI - In vitro and in vivo stability of oseltamivir within a bioequivalence trial. AB - A simple, precise, and rapid method to simultaneously determine the levels of oseltamivir (OS) and oseltamivir carboxylate (OSC) in human plasma was developed. Additionally, the stability of both substances in plasma was investigated under different conditions. The method involved protein precipitation (0.01 % HCl in acetonitrile), and then the supernatant was injected into the high-performance liquid chromatography (HPLC)-MS/MS. The chromatographic separation was achieved on a YMC-Triart C18 (100 * 2.0 mm, 5 MUm) column using acetonitrile/water (30:70, v/v) containing 0.1 % formic acid as the mobile phase. Sample volume was 5 MUl. The linearity of the method was established in the concentration range of 0.5-100 ng/mL for OS and 1.0-1000 ng/mL for OSC. The intra-day precision and accuracy for oseltamivir were 1.5-8.9 and 94.4-101.0 %, respectively. For oseltamivir carboxylate, the intra-day precision and accuracy were 3.2-12.7 and 92.8-108.8 %, respectively, whereas the inter-day precision and accuracy were 5.5-11.5 and 94.6 104.0 % for oseltamivir and 4.7-11.5 and 99.9-103.9 % for oseltamivir carboxylate, respectively. The application of this method was demonstrated by a bioequivalence study in 28 healthy humans with 75 mg oseltamivir phosphate capsules (Tamiflu(r)). Sodium fluoride (2.4 mg/mL) with potassium oxalate (3 mg/mL) was used as anticoagulant within sampling of trial. The assay reproducibility was established by reanalysis of 80 incurred samples. PMID- 27002613 TI - HS-GC/MS volatile profile of different varieties of garlic and their behavior under heating. AB - Garlic is one of the most used seasonings in the world whose beneficial health effects, mainly ascribed to organosulfur compounds, are shared with the rest of the Allium family. The fact that many of these compounds are volatile makes the evaluation of the volatile profile of garlic interesting. For this purpose, three garlic varieties-White, Purple, and Chinese-cultivated in the South of Spain were analyzed by a method based on a headspace (HS) device coupled to a gas chromatograph and mass detector (HS-GC/MS). The main temperatures in the HS were optimized to achieve the highest concentration of volatiles. A total number of 45 volatiles were tentatively identified (among them 17 were identified for the first time in garlic); then, all were classified, also for the first time, and their relative concentration in three garlic varieties was used to evaluate differences among them and to study their profiles according to the heating time. Chinese garlic was found to be the richest variety in sulfur volatiles, while the three varieties presented a similar trend under preset heating times allowing differentiation between varieties and heating time using principal component analysis. Graphical Abstract HS-GC/MS analysis of the volatile profile of garlic. PMID- 27002614 TI - The classification of recurrent spinal epidural hematoma: a review of the literature and a comparison with the cases. AB - Symptomatic postoperative spinal epidural hematoma (SEH) and spontaneous spinal epidural hematoma (SSEH) are both rare conditions, and recurrent SEH occurs even less frequently. Therefore, we describe a case of symptomatic postoperative SEH after surgical evacuation of SSEH, which was diagnosed using magnetic resonance imaging (MRI) and managed with negative pressure wound therapy (NPWT). The authors classified the reported recurrent SEHs into two types based on the cause of their previous hematoma, which can be classified as spontaneous or postoperative. The characteristics, diagnosis, managements, and results of recurrent SEHs were analyzed. The authors suggest that the postoperative SEH in the Type II will be treated with NPWT, and the new classification will be helpful for prognosis, diagnosis, and management of the recurrent SEHs. PMID- 27002615 TI - Ratio of lumbar 3-column osteotomy closure: patient-specific deformity characteristics and level of resection impact correction of truncal versus pelvic compensation. AB - PURPOSE: The resection point of a lumbar three-column osteotomy (3CO) creates separation of the spino-pelvic complex. This study investigates the impact of patients' baseline deformity and level of 3CO resection on the distribution of correction between the trunk and the pelvis following osteotomy closure. METHODS: Patients who underwent single lumbar 3CO, upper instrumented vertebra (UIV) T1 T10, and 6 month follow-up were included. The truncal and pelvic closures were calculated based on the vertebrae adjacent to the osteotomy level and the impact of radiographic parameters and level of 3CO on the closures were analyzed. RESULTS: 113 patients were included. Patients who experienced more pelvic correction had significantly higher Pelvic Tilt and lower Sagittal Vertical Axis at baseline. Patients who underwent more caudal osteotomies with higher pelvic compensation with modest SVA sustained more pelvic correction. CONCLUSIONS: The osteotomy closure is driven by patient's specific deformity. More caudal osteotomy level leads to greater pelvic tilt improvement. LEVEL OF EVIDENCE: III. PMID- 27002616 TI - A biomechanical analysis on the impact of episiotomy during childbirth. AB - Episiotomy is still a controversy issue among physicians, despite the enormous growth of clinical research. Therefore, the potential of numerical modeling of anatomical structures to simulate biomechanical processes was exploited to realize quantitatively the real effects of the episiotomy and its consequences on the pelvic floor muscle. As such, a numerical model was used composed of pelvic floor muscles, a surface delimiting the anterior region, and a fetus body. A normal vaginal delivery without and with different episiotomies was simulated with the fetus in vertex presentation and occipitoanterior position. According to our numerical results, a mediolateral episiotomy has a protective effect, reducing the stress on the muscles, and the force required to delivery successfully up to 52.2 %. The intervention also has benefits on muscle injury, reducing the damage to a small zone. This study demonstrates the feasibility of using a computational modeling approach to study parturition, namely the capability to isolate and evaluate the mechanical significance of a single feature. It must, however, be taken into account that the numerical model does not assess problems that may occur as blood loss, infections and others, so it is necessary to examine whether the benefits of an intervention outweigh the risks. PMID- 27002617 TI - Long non-coding RNA TUSC7 acts a molecular sponge for miR-10a and suppresses EMT in hepatocellular carcinoma. AB - Despite advances in the roles of long non-coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) in cancer biology, which has been identified as a tumor suppressor by regulating cell proliferation, apoptosis, migration, invasion, cell cycle, and tumor growth, the function of TUSC7 in hepatocellular carcinoma (HCC) remains unknown. In this study, we observed that the expression of TUSC7 was immensely decreased in HCC. Clinically, the lower expression of TUSC7 predicted poorer survival and may be an independent risk factor for HCC patients. Moreover, TUSC7 inhibited cell metastasis, invasion, and epithelial-to-mesenchymal transformation (EMT) through competitively binding miR-10a. Furthermore, we found that TUSC7 could decrease the expression of Eph tyrosine kinase receptor A4 (EphA4), a downstream target of miR-10a as well as an EMT suppressor, through TUSC7-miR-10a-EphA4 axis. Taken together, we demonstrate that TUSC7 suppresses EMT through the TUSC7-miR-10a-EphA4 axis, which may be a potential target for therapeutic intervention in HCC. PMID- 27002618 TI - Familial Hypercholesterolaemia in the Era of Genetic Testing. AB - Familial hypercholesterolaemia (FH) is a relatively common autosomal dominant genetic condition leading to premature ischaemic vascular disease and mortality if left untreated. Currently, a universal consensus on the diagnostic criteria of FH does not exist but the diagnosis of FH largely relies on the evaluation of low density lipoprotein-cholesterol (LDL-C) levels, a careful documentation of family history, and the identification of clinical features. Diagnosis based purely on lipid levels remains common but there are several limitations to this method of diagnosis both practically and in the proportion of false-negatives and false positives detected, resulting in substantial under-diagnosis of FH. In some countries, diagnostic algorithms are supplemented with genetic testing of the index case as well as genetic and lipid testing of relatives of the index case. Such "cascade" screening of families following identification of index cases appears to not only improve the rate of diagnosis but is also cost-effective. Currently, we observe a great variation in the excess mortality among patients with FH, which likely reflects a combination of additional genetic and environmental effects on risk overlaid on the risk associated with FH. Current accepted drug therapies for FH include statins and PSCK9 inhibitors. Further work is required to evaluate the cardiovascular disease risk in patients with genetically diagnosed FH and to determine whether a risk-based approach to the treatment of FH is appropriate. PMID- 27002619 TI - CETP Inhibition in CVD Prevention: an Actual Appraisal. AB - By virtue of their effects on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and cellular cholesterol efflux, there is considerable interest in the potential use of pharmacological inhibitors of cholesteryl ester transfer protein (CETP) as a novel approach for cardiovascular disease prevention. This is supported by observations from genetic and animal studies suggesting that less CETP activity has favorable cardiovascular effects. Despite the adverse effects of the first CETP inhibitor to move forward in clinical development, torcetrapib, there remains considerable interest in developing alternative CETP inhibitors without the off-target effects of torcetrapib. The clinical development programs leading to a number of promising CETP inhibitors will be reviewed. PMID- 27002620 TI - Clinical Approaches to the Patient with a Failing Fontan Procedure. AB - The Fontan operation has been nothing short of revolutionary in its influence on the modern management of patients born with functionally univentricular hearts. The vast majority of these individuals are now surviving well into adulthood. In the 45 years since its introduction, however, there has been increasing recognition of Fontan survivors as a vulnerable population with an altered physiology that has remarkably broad, adverse impact on their long-term health. In this review, the authors discuss the varied manifestations, both cardiac and extracardiac, of the failing Fontan circulation and potential therapeutic options. In addition, a general clinical approach to the patient presenting with Fontan failure is proposed. Ultimately, the key to improving our care and understanding of the Fontan population lies in multi-institutional collaboration and partnership between subspecialty cardiologists and specialists in other organ systems. PMID- 27002621 TI - Choosing Between MRI and CT Imaging in the Adult with Congenital Heart Disease. AB - Improvements in the outcomes of surgical and catheter-based interventions and medical therapy have led to a growing population of adult patients with congenital heart disease. Adult patients with previously undiagnosed congenital heart disease or those previously palliated or repaired may have challenging echocardiographic examinations. Understanding the distinct anatomic and hemodynamic features of the congenital anomaly and quantifying ventricular function and valvular dysfunction plays an important role in the management of these patients. Rapid advances in imaging technology with magnetic resonance imaging (MRI) and computed tomography angiography (CTA) allow for improved visualization of complex cardiac anatomy in the evaluation of this unique patient population. Although echocardiography remains the most widely used imaging tool to evaluate congenital heart disease, alternative and, at times, complimentary imaging modalities should be considered. When caring for adults with congenital heart disease, it is important to choose the proper imaging study that can answer the clinical question with the highest quality images, lowest risk to the patient, and in a cost-efficient manner. PMID- 27002622 TI - Left Ventricular Non-Compaction in Athletes: To Play or Not to Play. AB - Isolated left ventricular non-compaction (LVNC) has usually been viewed as a rare cardiomyopathy in athletes. However, with advances in diagnostic imaging techniques and increased use of pre-participation screening electrocardiograms (ECGs), apparent LVNC is being recognized in an increasing number of athletes. Given the lack of a true gold standard for diagnosis, significant debate continues regarding optimal diagnostic criteria. There are increasing data to support the possibility of over-diagnosing this cardiomyopathy in an athletic population due to the physiologic adaptation to the extreme preload and afterload characteristic of intense athletic participation. This appears to be particularly true in African-American or African-Caribbean athletes. The most common presenting symptom in the athlete with true LVNC is exertional syncope. Evaluation of the at-risk athlete will typically include a complete history, with attention to cardiac symptoms, family history of premature cardiovascular disease or sudden cardiac death (SCD), physical examination, 12-lead ECG, two-dimensional echocardiography, and, in some cases, cardiac magnetic resonance imaging with gadolinium contrast. In addition, stress echocardiography, 24- to 48-h Holter monitoring, or 30-day event monitoring for arrhythmias may be necessary to fully evaluate the athlete's risk. Adverse outcomes with LVNC include ventricular dysfunction, arrhythmias, syncope, SCD, and thromboembolism. Asymptomatic athletes with hypertrabeculation of the left ventricle but normal ventricular function likely do not require restrictions on activity. Symptomatic individuals who meet criteria for LVNC, especially those with abnormal ventricular function and exercise-induced symptoms or arrhythmias, should be prohibited from participating in vigorous sports activities. PMID- 27002623 TI - Does Habitual Physical Activity Increase the Sensitivity of the Appetite Control System? A Systematic Review. AB - BACKGROUND: It has been proposed that habitual physical activity improves appetite control; however, the evidence has never been systematically reviewed. OBJECTIVE: To examine whether appetite control (e.g. subjective appetite, appetite-related peptides, food intake) differs according to levels of physical activity. DATA SOURCES: Medline, Embase and SPORTDiscus were searched for articles published between 1996 and 2015, using keywords pertaining to physical activity, appetite, food intake and appetite-related peptides. STUDY SELECTION: Articles were included if they involved healthy non-smoking adults (aged 18-64 years) participating in cross-sectional studies examining appetite control in active and inactive individuals; or before and after exercise training in previously inactive individuals. STUDY APPRAISAL AND SYNTHESIS: Of 77 full-text articles assessed, 28 studies (14 cross-sectional; 14 exercise training) met the inclusion criteria. RESULTS: Appetite sensations and absolute energy intake did not differ consistently across studies. Active individuals had a greater ability to compensate for high-energy preloads through reductions in energy intake, in comparison with inactive controls. When physical activity level was graded across cross-sectional studies (low, medium, high, very high), a significant curvilinear effect on energy intake (z-scores) was observed. LIMITATIONS: Methodological issues existed concerning the small number of studies, lack of objective quantification of food intake, and various definitions used to define active and inactive individuals. CONCLUSION: Habitually active individuals showed improved compensation for the energy density of foods, but no consistent differences in appetite or absolute energy intake, in comparison with inactive individuals. This review supports a J-shaped relationship between physical activity level and energy intake. Further studies are required to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42015019696. PMID- 27002625 TI - Barriers Accessing Mental Health Services Among Culturally and Linguistically Diverse (CALD) Immigrant Women in Australia: Policy Implications. AB - Immigrant and refugee women from diverse ethnic backgrounds encounter multiple barriers in accessing mental healthcare in various settings. A systematic review on the prevalence of mental health disorders among culturally and linguistically diverse (CALD) women in Australia documented the following barriers: logistical, language and communication, dissonance between participants and care providers and preference for alternative interventions. This article proposes recommendations for policies to better address the mental health needs of immigrant and refugee women. Key policy recommendations include: support for gender specific research, implementation and evaluation of transcultural policies, cultural responsiveness in service delivery, review of immigration and refugee claims policies and social integration of immigrants. PMID- 27002624 TI - Weight Loss Success Among Overweight and Obese Women of Mexican-Origin Living in Mexico and the United States: A Comparison of Two National Surveys. AB - We assessed variations in and correlates of weight-loss success (WLS) among overweight/obese women in Mexico (WIMX) and Mexican-American women (MA). We used cross-national data from 2006 ENSANUT (Mexico) and NHANES (2001-2008) to compare 5061 WIMX with 550 MA's without known metabolic conditions. WLS was defined as losing >=5 % of body weight over 1 year. MA's were more likely to attain WLS (OR 1.31; 95 % CI 1.01-1.70). WLS among WIMX was higher in those with at least high school, a provider screen of overweight and a lower BMI. Among MA's, an incomplete high school versus primary education reduced the odds of WLS. Among women who lost >=10 lbs, weight-loss strategies such as eating less were higher among MA's. MA women were more likely than WIMX to attain WLS. Understanding these disparities can help design customized public health interventions that curb the obesity epidemic in these women in both countries. PMID- 27002626 TI - Morbidity, Self-Perceived Health and Mortality Among non-Western Immigrants and Their Descendants in Denmark in a Life Phase Perspective. AB - To enable preventive policies to address health inequity across ethnic groups, this review overviews the current knowledge on morbidity, self-perceived health and mortality among non-Western immigrants and their descendants in Denmark. A systematic search in PUBMED, SCOPUS, Embase and Cochrane as well as in national databases was undertaken. The final number of publications included was 45. Adult immigrants had higher morbidity, but lower mortality compared to ethnic Danes. Immigrant children had higher mortality and morbidity compared to ethnic Danes. Immigrants' health is critical to reach the political goals of integration. Despite non-Western immigrants' higher morbidity than ethnic Danes, no national strategy targeting immigrants' health has been implemented. Future research should include elderly immigrants and children, preferably employing a life course perspective to enhance understanding of parallel processes of societal adaptation and health. PMID- 27002627 TI - Elevation of NT-proBNP and cardiac troponins in sepsis-related deaths: a forensic perspective. AB - In the present study, the levels of NT-proBNP, troponin T, and troponin I were measured in postmortem serum from femoral blood in a series of sepsis-related fatalities that had undergone forensic autopsies. We aimed to assess whether a possible increase in the concentrations of these biomarkers was correlated to macroscopic or microscopic observations that suggest myocardial damage or cardiac dysfunction. Two study groups were retrospectively formed, a sepsis-related fatalities group and a control group. Both groups consisted of 16 forensic autopsy cases. Unenhanced computed tomography scan, autopsy, histological, toxicological, microbiological, and biochemical analyses were performed for all cases in both groups. Levels of procalcitonin, C-reactive protein, NT-proBNP, troponin T, and troponin I were systematically measured in postmortem serum from femoral blood. The preliminary results suggest that the postmortem serum troponin I, troponin T, and NT-proBNP levels are increased in sepsis-related deaths in the absence of any relevant coronary artery disease, myocardial ischemia, or signs of heart failure. These findings corroborate clinical data from previous studies pertaining to the usefulness of troponins and natriuretic peptides as indicators of toxic and inflammatory damage to the heart in cases of severe sepsis and septic shock without concomitant underlying coronary syndromes. PMID- 27002628 TI - Validation of the sex estimation method elaborated by Schutkowski in the Granada Osteological Collection of identified infant and young children: Analysis of the controversy between the different ways of analyzing and interpreting the results. AB - Sex estimation of juveniles in the Physical and Forensic Anthropology context is currently a task with serious difficulties because the discriminatory bone characteristics are minimal until puberty. Also, the small number of osteological collections of children available for research has made it difficult to develop effective methodologies in this regard. This study tested the characteristics of the ilium and jaw proposed by Schutkowski in 1993 for estimation of sex in subadults. The study sample consisted of 109 boys and 76 girls, ranging in age from 5 months of gestation to 6 years, from the identified osteological collection of Granada (Spain). For the analysis and interpretation of the results, we have proposed changes from previous studies because we believe they raised methodological errors relating to the calculation of probabilities of success and sex distribution in the sample. The results showed correct assignment probabilities much lower than those obtained by Schutkowski as well as by other authors. The best results were obtained with the angle and depth of the sciatic notch, with 0.73 and 0.80 probability of correct assignment respectively if the male trait was observed. The results obtained with the other criteria were too small to be valid in the context of Physical or Forensic Anthropology. From our results, we concluded that Schutkowski method should not be used in forensic context, and that the sciatic notch is the most dimorphic trait in subadults and, therefore, the most appropriate to develop more effective methods for estimating sex. PMID- 27002629 TI - Molecular Analysis of South African Ovine Herpesvirus 2 Strains Based on Selected Glycoprotein and Tegument Genes. AB - Ovine herpesvirus 2 (OvHV-2), is the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), a generally fatal disease of cattle and other captive wild ruminants. Information on the OvHV-2 strains circulating in South Africa (SA) and other African countries with regard to genetic structure and diversity, and pattern of distribution is not available. This study aimed to characterize the OvHV-2 strains circulating in SA using selected genes encoding glycoproteins and tegument proteins. To establish the genetic diversity of OvHV-2 strains, four genes, Ov 7, Ov 8 ex2, ORF 27 and ORF 73 were selected for analysis by PCR and DNA sequencing. Nucleotide and amino acid multiple sequence analyses revealed two genotypes for ORF 27 and ORF 73, and three genotypes for Ov 7 and Ov 8 ex2, randomly distributed throughout the regions. Ov 7 and ORF 27 nucleotide sequence analysis revealed variations that distinguished SA genotypes from those of reference OvHV-2 strains. Epitope mapping analysis showed that mutations identified from the investigated genes are not likely to affect the functions of the gene products, particularly those responsible for antibody binding activities associated with B-cell epitopes. Knowledge of the extent of genetic diversity existing among OvHV-2 strains has provided an understanding on the distribution patterns of OvHV-2 strains or genotypes across the regions of South Africa. This can facilitate the management of SA-MCF in SA, in terms of introduction of control measures or safe practices to monitor and control OvHV-2 infection. The products encoded by the Ov 7, Ov 8 ex2 and ORF 27 genes are recommended for evaluation of their coded proteins as possible antigens in the development of an OvHV-2 specific serodiagnostic assay. PMID- 27002630 TI - Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C. AB - Fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac-2 bp) are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F >= 2). In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F >= 3). In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB4) index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC) was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C. PMID- 27002631 TI - Expectation-Maximization Binary Clustering for Behavioural Annotation. AB - The growing capacity to process and store animal tracks has spurred the development of new methods to segment animal trajectories into elementary units of movement. Key challenges for movement trajectory segmentation are to (i) minimize the need of supervision, (ii) reduce computational costs, (iii) minimize the need of prior assumptions (e.g. simple parametrizations), and (iv) capture biologically meaningful semantics, useful across a broad range of species. We introduce the Expectation-Maximization binary Clustering (EMbC), a general purpose, unsupervised approach to multivariate data clustering. The EMbC is a variant of the Expectation-Maximization Clustering (EMC), a clustering algorithm based on the maximum likelihood estimation of a Gaussian mixture model. This is an iterative algorithm with a closed form step solution and hence a reasonable computational cost. The method looks for a good compromise between statistical soundness and ease and generality of use (by minimizing prior assumptions and favouring the semantic interpretation of the final clustering). Here we focus on the suitability of the EMbC algorithm for behavioural annotation of movement data. We show and discuss the EMbC outputs in both simulated trajectories and empirical movement trajectories including different species and different tracking methodologies. We use synthetic trajectories to assess the performance of EMbC compared to classic EMC and Hidden Markov Models. Empirical trajectories allow us to explore the robustness of the EMbC to data loss and data inaccuracies, and assess the relationship between EMbC output and expert label assignments. Additionally, we suggest a smoothing procedure to account for temporal correlations among labels, and a proper visualization of the output for movement trajectories. Our algorithm is available as an R-package with a set of complementary functions to ease the analysis. PMID- 27002632 TI - Evaluation of carotid artery intima-media thickness in patients with moderate-to severe obstructive sleep apnea syndrome after nasal surgery and uvulopalatopharyngoplasty. PMID- 27002633 TI - Clinical progression of ocular injury following arsenical vesicant lewisite exposure. AB - Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2 mg/L) vapor for 2.5, 5.0, 7.5 and 10.0 min and clinical progression of injury was observed for 28 days post-exposure (dose-response study), or exposed to same LEW dose for 2.5 and 7.5 min and clinical progression of injury was observed for up to 56 days post-exposure (time-response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6 h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1 day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22-35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury. PMID- 27002634 TI - Health Insurance Coverage and Hypertension Control in China: Results from the China Health and Nutrition Survey. AB - BACKGROUND: China has rapidly expanded health insurance coverage over the past decade but its impact on hypertension control is not well known. We analyzed factors associated with hypertension and the impact of health insurance on the management of hypertension in China from 1991 to 2009. METHODS AND FINDINGS: We used individual-level data from the China Health and Nutrition Survey (CHNS) for blood pressure, BMI, and other socio-economic variables. We employed multi-level logistic regression models to estimate the factors associated with prevalence and management of hypertension. We also estimated the effects of health insurance on management of hypertension using propensity score matching. We found that prevalence of hypertension increased from 23.8% (95% CI: 22.5-25.1%) in 1991 to 31.5% (28.5-34.7%) in 2009. The proportion of hypertensive patients aware of their condition increased from 31.7% (28.7-34.9%) to 51.1% (45.1-57.0%). The proportion of diagnosed hypertensive patients in treatment increased by 35.5% in the 19 years, while the proportion of those in treatment with controlled blood pressure remained low. Among diagnosed hypertensives, health insurance increased the probability of receiving treatment by 28.7% (95% CI: 10.6-46.7%) compared to propensity-matched individuals not covered by health insurance. CONCLUSIONS: Hypertension continues to be a major health threat in China and effective control has not improved over time despite large improvements in awareness and treatment access. This suggests problems in treatment quality, medication adherence and patient understanding of the condition. Improvements in hypertension management, quality of medical care for those at high risk, and better health insurance packages are needed. PMID- 27002636 TI - MAPK Activation Is Essential for Waddlia chondrophila Induced CXCL8 Expression in Human Epithelial Cells. AB - BACKGROUND: Waddlia chondrophila (W. chondrophila) is an emerging agent of respiratory and reproductive disease in humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial agents, such as Chlamydia abortus (C. abortus). The current study investigated the growth characteristics and innate immune responses of human and ruminant epithelial cells in response to infection with W. chondrophila. METHODS: Human epithelial cells (HEp2) were infected with W. chondrophila for 24h. CXCL8 release was significantly elevated in each of the cell lines by active-infection with live W. chondrophila, but not by exposure to UV-killed organisms. Inhibition of either p38 or p42/44 MAPK significantly inhibited the stimulation of CXCL8 release in each of the cell lines. To determine the pattern recognition receptor through which CXCL8 release was stimulated, wild-type HEK293 cells which express no TLR2, TLR4, NOD2 and only negligible NOD1 were infected with live organisms. A significant increase in CXCL8 was observed. CONCLUSIONS/SIGNIFICANCE: W. chondrophila actively infects and replicates within both human and ruminant epithelial cells stimulating CXCL8 release. Release of CXCL8 is significantly inhibited by inhibition of either p38 or p42/44 MAPK indicating a role for this pathway in the innate immune response to W. chondrophila infection. W. chondrophila stimulation of CXCL8 secretion in HEK293 cells indicates that TLR2, TLR4, NOD2 and NOD1 receptors are not essential to the innate immune response to infection. PMID- 27002637 TI - Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data. AB - Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths. PMID- 27002638 TI - Establishment and Maintenance of Primary Fibroblast Repositories for Rare Diseases-Friedreich's Ataxia Example. AB - Friedreich's ataxia (FRDA) represents a rare neurodegenerative disease caused by expansion of GAA trinucleotide repeats in the first intron of the FXN gene. The number of GAA repeats in FRDA patients varies from approximately 60 to <1000 and is tightly correlated with age of onset and severity of the disease symptoms. The heterogeneity of Friedreich's ataxia stresses the need for a large cohort of patient samples to conduct studies addressing the mechanism of disease pathogenesis or evaluate novel therapeutic candidates. Herein, we report the establishment and characterization of an FRDA fibroblast repository, which currently includes 50 primary cell lines derived from FRDA patients and seven lines from mutation carriers. These cells are also a source for generating induced pluripotent stem cell (iPSC) lines by reprogramming, as well as disease relevant neuronal, cardiac, and pancreatic cells that can then be differentiated from the iPSCs. All FRDA and carrier lines are derived using a standard operating procedure and characterized to confirm mutation status, as well as expression of FXN mRNA and protein. Consideration and significance of creating disease-focused cell line and tissue repositories, especially in the context of rare and heterogeneous disorders, are presented. Although the economic aspect of creating and maintaining such repositories is important, the benefits of easy access to a collection of well-characterized cell lines for the purpose of drug discovery or disease mechanism studies overshadow the associated costs. Importantly, all FRDA fibroblast cell lines collected in our repository are available to the scientific community. PMID- 27002635 TI - Bloodstream infections in neutropenic cancer patients: A practical update. AB - Bloodstream infections (BSI) are among the most frequent complications in neutropenic cancer patients and, if caused by Gram-negative rods, are associated with high mortality. Thus, fever during neutropenia warrants prompt empirical antibiotic therapy which should be active against the most frequent Gram negatives. In the last decade, there has been a worldwide increase in multidrug resistant (MDR) strains. In these cases, the traditional choices such as oral therapy, ceftazidime, cefepime, piperacillin-tazobactam, or even carbapenems, might be ineffective. Therefore novel de-escalation approach has been proposed for patients who are at high risk for infections due to MDR bacteria. It consists of starting antibiotics which cover the most probable resistant strain but it is narrowed down after 72 hours if no MDR pathogen is isolated. With increasing bacterial resistance, the benefit of fluoroquinolone prophylaxis during prolonged neutropenia remains to be confirmed. Antibiotic stewardship and infection control programs are mandatory in every cancer center. PMID- 27002639 TI - On the Ecology and Conservation of Sericinus montelus (Lepidoptera: Papilionidae) - Its Threats in Xiaolongshan Forests Area (China). AB - CONTENTS AND METHODS: Here we present a detailed analysis of the life history, mobility and habitat requirements of the butterfly Sericinus montelus on the basis of extensive field observations, experimental breeding, capture-mark- recapture (CMR) and transect surveys. LIFE HISTORY: We found that S. montelus has three generations per year and overwinters as pupae on shrub branches in Xiaolongshan. The adults of first generation have a peak of emergence in late April. The second generation emerges at the end of June and the third in early to middle August. Within the study region, larvae of S. montelus are monophagous on Aristolochia contorta. Adults fly slowly and lay eggs in clusters. KEY FACTORS: Life tables show that natural enemies and human activities such as mowing, weeding and trampling during the egg and larval stages are key factors causing high mortality, killing up to 43% of eggs and 72% of larvae thereby limiting population growth and recovery. POPULATION ECOLOGY: The populations of S. montelus in Xiaolongshan have a rather patchy distribution. According to CMR data, adults fly a maximum distance of 700m within a lifespan of 6 days. The host plant A. contorta, grows along the low banks of fields, irrigation ditches and paths, and can be highly affected by agricultural activities, like mowing, weeding and herding, which impact larval survival. POPULATION MAINTENANCE: For S. montelus should mainly focus on reducing agricultural threats to the host plant A. contorta and on increasing habitat connectivity. PMID- 27002640 TI - Changes in the clinical features of child and adolescent psychiatric inpatients: a nationwide time-trend study from Finland. AB - BACKGROUND: Few studies have focused on the recent trends in clinical features child and adolescent inpatient. AIMS: This study focuses on the change in the characteristics of child and adolescent psychiatric inpatients in Finland. METHODS: The data collection was carried out on selected study days in 2000 and 2011. Questionnaires were sent to the psychiatrists of all child and adolescent wards in Finland. RESULTS: By comparing the data obtained in 2000 (n = 504) and 2011 (n = 412), several changes were found: the percentage of girls in adolescent wards grew and the diagnoses of depression, anxiety disorders, attention deficit hyperactivity disorder and eating disorders increased. In contrast, the diagnoses of psychosis and conduct or oppositional disorders decreased. General functioning was evaluated with the Childrens Global Assessment Scale (CGAS). There were no changes in the distribution of CGAS scores among child inpatients, whereas among adolescents the share of inpatients with lowest CGAS scores (1-30) increased significantly. The mean length of stay dropped. CONCLUSIONS: The growing percentage of girls in adolescent wards is associated with an increase in diagnoses that are more prevalent among girls than boys, namely depression, anxiety, and eating disorders. The changes in the distribution of diagnoses may be due to changes in diagnostic or referral practices, or reflect true changes in the prevalence of disorders among children and adolescents in need of inpatient treatment. The share of adolescent inpatients with the poorest general functioning has increased. The observed shortening in inpatient treatment time seems to be a result of changes in treatment practices. PMID- 27002641 TI - Controlled release of curcumin from poly(HEMA-MAPA) membrane. AB - In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 degrees C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h. PMID- 27002642 TI - Optimizing the Histological Diagnosis of Adenomyosis Using in vitro Three Dimensional Ultrasonography. AB - The use of in vitro three-dimensional ultrasound examination with needle stereotaxis after hysterectomy is illustrated in a case of extensive adenomyosis. The quality of the images at in vitro ultrasonography was compared with the quality of the images obtained at the preoperative ultrasound examination. The ultrasound findings were compared with the macroscopical and the microscopical examination. This new approach helps in indicating the precise location of the preoperatively identified adenomyosis lesions to the pathologist. This may optimize the diagnostic accuracy of the histological examination in women with adenomyosis. PMID- 27002643 TI - The Effects of Arsenic Trioxide in Combination with Retinoic Acids on Cutaneous T Cell Lymphoma Cell Lines. AB - Cutaneous T-cell lymphomas (CTCL) are characterized by an infiltration of the skin with malignant T cells. Curative treatments for aggressive entities such as Sezary syndrome have not been identified yet. Arsenic trioxide (AsO3) is used for the treatment of acute promyelocytic leukemia in combination with retinoids. As the latter are established treatment options in CTCL, we sought to evaluate the efficacy of AsO3 for mono- and combination therapy in vitro. Analyses for apoptosis, cell cycle inhibition, cytotoxicity and cell viability were made after incubation of CTCL cells with AsO3 alone or in combination with the retinoids all trans-retinoic acid or bexarotene. While AsO3 induced apoptosis, retinoids did not at the time point of analysis. However, retinoids strongly reduced cell viability. Due to the efficient apoptosis induction, AsO3 might be a potentially suitable agent for CTCL treatment, although this effect was not increased by retinoids. PMID- 27002644 TI - A novel fluorescent protein from the deep-sea anemone Cribrinopsis japonica (Anthozoa: Actiniaria). AB - A fluorescent protein was identified and cloned from the deep-sea anemone Cribrinopsis japonica. Bioluminescence and fluorescence expression were examined by direct observations of live specimens and RNA-Seq analysis. Both approaches revealed a novel green fluorescent protein in the tentacles of the anemone, but bioluminescence was not observed. Behavioural observations revealed that a blue light excited the fluorescence in the tentacles, and initiated a behavioural response whereby the fluorescent tentacles became fully exposed to the blue light. The excitation and emission peaks of C. japonica's fluorescent protein were at 500 and 510 nm, respectively, which were greener than those reported in homologs. Furthermore, this protein was highly tolerant of increased temperatures and repeated freeze-thaw treatments. The current study presents an example of fluorescence in a deep-sea cnidarian, demonstrating that fluorescent proteins could have important roles, regardless of the presence or absence of strong sunlight. It also demonstrates that this deep-sea fluorescent protein has unique characteristics, including high stability, perhaps as an adaptation to the extreme environment. PMID- 27002645 TI - The Effect of Prior Caffeine Consumption on Neuropsychological Test Performance: A Placebo-Controlled Study. AB - BACKGROUND: The aim of this study was to investigate whether the prior consumption of 200 mg of pure caffeine affected neuropsychological test scores in a group of elderly participants aged over 60 years. METHOD: Using a double-blind placebo versus caffeine design, participants were randomly assigned to receive 200 mg of caffeine or placebo. A neuropsychological assessment testing the domains of general cognitive function, processing speed, semantic memory, episodic memory, executive function, working memory and short-term memory was carried out. RESULTS: Significant interaction effects between age, caffeine and scores of executive function and processing speed were found; participants who had received caffeine showed a decline in performance with increasing age. This effect was not seen for participants who received placebo. CONCLUSION: The results highlight the need to consider and control prior caffeine consumption when scoring neuropsychological assessments in the elderly, which is important for accuracy of diagnosis and corresponding normative data. PMID- 27002648 TI - Eugenol in combination with lactic acid bacteria attenuates Listeria monocytogenes virulence in vitro and in invertebrate model Galleria mellonella. AB - Listeria monocytogenes is a human enteric pathogen that causes severe foodborne illness in high-risk populations. Crossing the intestinal barrier is the first critical step for Listeria monocytogenes infection. Therefore, reducing L. monocytogenes colonization and invasion of intestinal epithelium and production of virulence factors could potentially control listeriosis in humans. This study investigated the efficacy of sub-inhibitory concentration (SIC) of the plant derived antimicrobial eugenol, either alone, or in combination with five lactic acid bacteria (LAB), namely Bifidobacterium bifidum (NRRL-B41410), Lactobacillus reuteri (B-14172), Lactobacillus fermentum (B-1840), Lactobacillus plantarum (B 4496) and Lactococcus lactis subspecies lactis (B-633) in reducing Listeria monocytogenes adhesion to and invasion of human intestinal epithelial cells (Caco 2). Additionally, the effect of the aforementioned treatments on Listeria monocytogenes listeriolysin production, epithelial E-cadherin binding and expression of virulence genes was investigated. Moreover, the in vivo efficacy of eugenol-LAB treatments in reducing Listeria monocytogenes virulence in the invertebrate model Galleria mellonella was studied. Eugenol and LAB, either alone or in combination, significantly reduced Listeria monocytogenes adhesion to and invasion of intestinal cells (P < 0.05). Moreover, eugenol-LAB treatments decreased Listeria monocytogenes haemolysin production, E-cadherin binding and virulence gene expression (P < 0.05). In addition, the eugenol-LAB treatments significantly enhanced the survival rates of G. mellonella infected with lethal doses of Listeria monocytogenes (P < 0.05). The results highlight the antilisterial effect of eugenol either alone or in combination with LAB, and justify further investigations in a mammalian model. PMID- 27002649 TI - Designing and validation of a yoga-based intervention for schizophrenia. AB - CONTEXT: Schizophrenia is a chronic mental illness which causes significant distress and dysfunction. Yoga has been found to be effective as an add-on therapy in schizophrenia. Modules of yoga used in previous studies were based on individual researcher's experience. AIM: This study aimed to develop and validate a specific generic yoga-based intervention module for patients with schizophrenia. The study was conducted at NIMHANS Integrated Centre for Yoga (NICY). MATERIALS AND METHODS: A yoga module was designed based on traditional and contemporary yoga literature as well as published studies. The yoga module along with three case vignettes of adult patients with schizophrenia was sent to 10 yoga experts for their validation. RESULTS: Experts (n = 10) gave their opinion on the usefulness of a yoga module for patients with schizophrenia with some modifications. In total, 87% (13 of 15 items) of the items in the initial module were retained, with modification in the remainder as suggested by the experts. CONCLUSION: A specific yoga-based module for schizophrenia was designed and validated by experts. Further studies are needed to confirm efficacy and clinical utility of the module. Additional clinical validation is suggested. PMID- 27002651 TI - Optimising the diagnosis of ectopic pregnancy. AB - This retrospective cohort study reviewed the diagnosis of all ectopic pregnancies within a district general hospital over a 5-year period after the establishment of a dedicated Early Pregnancy Assessment Unit (EPAU). Of 215 ectopic pregnancies identified, notes were available for 208 (97%). Two-hundred and two cases were determined to have been diagnosed and managed as ectopic pregnancies. Six cases were excluded as they were pregnancies of unknown location managed as such. Overall, 91% were diagnosed by ultrasound scan, 5% were diagnosed clinically and 3% were diagnosed on serial human chorionic gonadotrophin (hCG) levels. This study found that the introduction of a dedicated, multi-professional, EPAU with a stable workforce improved ultrasound visualisation of ectopic pregnancies at first ultrasound scan from 22% prior to its commencement, to 61% over this period. The improvement in positive scan diagnosis of ectopic pregnancy was associated with a reduction in negative laparoscopy rate from 13% to 6%. PMID- 27002653 TI - Controlled chiral electrochromism of polyoxometalates incorporated in supramolecular complexes. AB - A three-component supramolecular system was constructed by combining host-guest recognition and electrostatic interaction for realization of induced circular dichroism of achiral polyanionic clusters in aqueous solution, while the induced chiral heteropoly blue was built and switched off by controlling the redox of the inorganic component via electrochemistry. PMID- 27002652 TI - Genomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria. AB - African apes harbour at least six Plasmodium species of the subgenus Laverania, one of which gave rise to human Plasmodium falciparum. Here we use a selective amplification strategy to sequence the genome of chimpanzee parasites classified as Plasmodium reichenowi and Plasmodium gaboni based on the subgenomic fragments. Genome-wide analyses show that these parasites indeed represent distinct species, with no evidence of cross-species mating. Both P. reichenowi and P. gaboni are 10 fold more diverse than P. falciparum, indicating a very recent origin of the human parasite. We also find a remarkable Laverania-specific expansion of a multigene family involved in erythrocyte remodelling, and show that a short region on chromosome 4, which encodes two essential invasion genes, was horizontally transferred into a recent P. falciparum ancestor. Our results validate the selective amplification strategy for characterizing cryptic pathogen species, and reveal evolutionary events that likely predisposed the precursor of P. falciparum to colonize humans. PMID- 27002655 TI - Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models. AB - After decades of sociopolitical obstacles, the field of psychiatry is experiencing a revived interest in the use of hallucinogenic agents to treat brain disorders. Along with the use of ketamine for depression, recent pilot studies have highlighted the efficacy of classic serotonergic hallucinogens, such as lysergic acid diethylamide and psilocybin, in treating addiction, post traumatic stress disorder, and anxiety. However, many basic pharmacological and toxicological questions remain unanswered with regard to these compounds. In this study, we discuss psychedelic medicine as well as the behavioral and toxicological effects of hallucinogenic drugs in zebrafish. We emphasize this aquatic organism as a model ideally suited to assess both the potential toxic and therapeutic effects of major known classes of hallucinogenic compounds. In addition, novel drugs with hallucinogenic properties can be efficiently screened using zebrafish models. Well-designed preclinical studies utilizing zebrafish can contribute to the reemerging treatment paradigm of psychedelic medicine, leading to new avenues of clinical exploration for psychiatric disorders. PMID- 27002654 TI - Ferritinophagy drives uropathogenic Escherichia coli persistence in bladder epithelial cells. AB - Autophagy is a cellular recycling pathway, which in many cases, protects host cells from infections by degrading pathogens. However, uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections (UTIs), persist within the urinary tract epithelium (urothelium) by forming reservoirs within autophagosomes. Iron is a critical nutrient for both host and pathogen, and regulation of iron availability is a key host defense against pathogens. Iron homeostasis depends on the shuttling of iron-bound ferritin to the lysosome for recycling, a process termed ferritinophagy (a form of selective autophagy). Here, we demonstrate for the first time that UPEC shuttles with ferritin-bound iron into the autophagosomal and lysosomal compartments within the urothelium. Iron overload in urothelial cells induces ferritinophagy in an NCOA4-dependent manner causing increased iron availability for UPEC, triggering bacterial overproliferation and host cell death. Addition of even moderate levels of iron is sufficient to increase and prolong bacterial burden. Furthermore, we show that lysosomal damage due to iron overload is the specific mechanism causing host cell death. Significantly, we demonstrate that host cell death and bacterial burden can be reversed by inhibition of autophagy or inhibition of iron-regulatory proteins, or chelation of iron. Together, our findings suggest that UPEC persist in host cells by taking advantage of ferritinophagy. Thus, modulation of iron levels in the bladder may provide a therapeutic avenue to controlling UPEC persistence, epithelial cell death, and recurrent UTIs. PMID- 27002660 TI - Prevalence causes and impact of work related musculoskeletal disorders among physical therapists. AB - BACKGROUND: Physical therapists are particularly vulnerable to work-related musculoskeletal disorders (WRMDs). OBJECTIVE: To evaluate the prevalence, causes and impact of WRMDs among physical therapists in the Kingdom of Saudi Arabia (KSA). METHODS: A cross-sectional study of physical therapists using a valid and reliable questionnaire. A total of 690 completed surveys were returned (response rate = 69%). The T-test and Pearson's correlation were used to identify correlations between variables and the incidence of WRMDs. RESULTS: Working hours/week and WRMDs were significantly correlated (p = 0.005). Lower back (46.5%) and neck (26.6%) pain were most commonly encountered. WRMDs were significantly correlated with altered work habits (p = 0.036) but not with body mass index (p = 0.297). The prevalence of WRMDs among physical therapists was 47.7% with a significant difference between full- and part-time practice (p = 0.023). Adjustable beds/plinths (20%) and splints (18%) were the most commonly used assistive devices. CONCLUSIONS: Physical therapists are especially vulnerable to WRMDs with a prevalence of 47.7%. WRMDs are impacted by both work status and setting. Low back pain is the most common form of WRMDs (46.5%). Avoidance of poor work habits, increased ergonomic awareness and application of safety measures are essential to prevent WRMDs. PMID- 27002656 TI - Sphingosine kinase 1/sphingosine-1-phosphate regulates the expression of interleukin-17A in activated microglia in cerebral ischemia/reperfusion. AB - BACKGROUND: Microglial activation is one of the causative factors of neuroinflammation in cerebral ischemia/reperfusion (IR). Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P), plays an important role in the regulation of proinflammatory cytokines in activated microglia. Recent research demonstrated that S1P increased IL-17A-secretion and then worsened CNS (central nervous system) inflammation. Thus, in the present study, we sought to use microglial cells as the object of study to discuss the molecular mechanisms in Sphk1/S1P regulated IL-17A-secretion in IR. METHODS: We used immunofluorescence and confocal microscopy to detect whether Sphk1 is expressed in microglia after cerebral IR or oxygen-glucose deprivation (OGDR). Western blot analysis was used to estimate the total Sphk1 protein level at different time points after OGDR. To detect cytokine secretion in microglial supernatants in response to OGDR, we measured the concentration of IL-17A in the culture supernatants using an enzyme linked immunosorbent assay (ELISA). To evaluate whether microglia subjected to OGDR exhibited neuronal injury, we used a commercially available terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) kit to detect apoptotic neurons. RESULTS: Sphk1 was expressed in microglia in response to cerebral IR or OGDR at appointed time. Pre-injection with PF-543, an inhibitor of Sphk1, before IR clearly reduced the expression of Sphk1 in microglia relative to brain IR alone. The number of TUNEL-positive neurons was also decreased in the PF-543-pretreated animals before IR compared to the animals with IR alone. When S1P was administered in OGDR microglia, IL-17A expression and neuronal apoptosis were increased compared to OGDR alone and the administration of S1P alone. ELISA further confirmed the above results. Moreover, the inhibition of Sphk1 by siRNA reduced IL-17A production and relieved neuronal apoptosis in OGDR microglia. CONCLUSION: These results indicated that Sphk1/S1P regulates the expression of IL-17A in activated microglia, inducing neuronal apoptosis in cerebral ischemia/reperfusion. The microglial Sphk1/S1P pathway may thus be a potential therapeutic target to control neuroinflammation in brain IR. PMID- 27002661 TI - Ligamentum flavum thickening at lumbar spine is associated with facet joint degeneration: An MRI study. AB - OBJECTIVE: Degenerative changes in posterior elements of the spine such as thickening or hypertrophy of the ligamentum flavum (LF) may result in spinal stenosis. In the present study, we aimed to investigate the potential factors including age, intervertebral disc degeneration (IDD), facet joint degeneration (FJD), end plate degeneration (EPD), which may affect LF thickening and to reveal the relationship among those factors at each level of lumbar spine by evaluating the magnetic resonance images (MRI). METHODS: A total of 200 individuals with low back and/or leg pain complaints who had undergone lumbar MRI were included in this study. The thickness of LF, FJD, IDD and EPD were assessed at all lumbar levels. RESULTS: Totally 1000 end plates, 1000 intervertebral discs and 2000 facet joints were evaluated and the thicknesses of 2000 LFs were measured from MRI images of 200 patients (100 males and 100 females). The mean age was 46.87 +/ 12.47 years. LF thickness was strongly associated with FJD especially on the ipsilateral side. Age and IDD were correlated at whole vertebral levels. The age related changes (LF thickness, FJD, IDD and EPD) were more prominent at L4-L5 vertebral level. However, gender had no effect on LF thickness. CONCLUSION: The results of this study suggest that LF thickening may occur independently or could be associated with FJD especially on the ipsilateral side and this relationship is due to the vertebral level. The degree of disc degeneration increases with age and age related changes may be predominantly observed at L4-L5 vertebral level. PMID- 27002662 TI - Continuous passive motion in adhesive capsulitis patients with diabetes mellitus: A randomized controlled trial. AB - BACKGROUND: The aim of this study was to clarify the effects of continuous passive motion (CPM) treatment on adhesive capsulitis (AC) in diabetes mellitus (DM) patients. METHODS: Forty-one DM patients with AC were randomized to two treatment groups. The first group (n= 20) (CPM group) received CPM treatments; the second group (n= 21) had conventional physical therapy (CPT group), including active stretching, range of motion (ROM) and pendulum exercises. All patients received electrotherapy. After a four-week-long physical therapy program, the patients were instructed to continue with an eight-week home exercise program. The patients rated the pain they felt at night, both while at rest and in motion, in the past week using the visual analogue scale (VAS). Functional outcome evaluations were performed using the Constant Shoulder Score (CSS) and Shoulder Pain and Disability Index (SPADI). All patients were evaluated at baseline, and during the fourth and twelfth weeks of the study. RESULTS: There were significant improvements in both groups' active and passive ROM for the shoulder, VAS measures, SPADI pain and disability scores and CSS, and excluding the active and passive internal and external rotation of shoulder increased with both treatment methods (CPM or CPT) over time (p< 0.001), however these differences were found to be prominent in patients receiving CPM therapy. CONCLUSIONS: Both the CPM and CPT therapies seemed to be beneficial for the treatment of AC in DM patients, however CPM revealed more distinctive improvements in the function and pain levels of the AC patients. PMID- 27002663 TI - Does proprioceptive acuity during active knee rotation in the transverse plane vary at different ranges? AB - BACKGROUND: Knee proprioception in the sagittal plane has been widely investigated in prospective studies, however limited information is known about proprioceptive acuity during active knee rotation and the way most commonly injured. OBJECTIVE: To investigate whether proprioceptive acuity during active internal and external knee rotation varies at different ranges in the transverse plane. METHODS: Healthy volunteers (N: 26) without previous injury or surgery of the knee joint participated in the study.Knee rotation proprioceptive acuity was measured using a custom-designed device. The measure of proprioceptive acuity used in this study was the just-noticeable-difference (JND). Participants actively rotated the knee at different intervals(initial, mid, and terminal internal or external rotation range) to one of four movement blocks and the magnitude of the permitted motion was judged. RESULTS: The means of the JND for proprioceptive acuity at initial internal rotation (0.80 degrees +/- 0.06) were significantly (p< 0.002) lower than for mid (1.62 degrees +/- 0.18), and terminal (2.08 degrees +/- 0.35) internal rotation. The means of the JND for proprioceptive acuity at initial external rotation (1.16 degrees +/- 0.10) were significantly (p< 0.04) lower than for mid (1.95 degrees +/- 0.30), and terminal (1.97 degrees +/- 0.24) internal rotation. CONCLUSIONS: Participants perceived smaller differences between active internal and external rotation movements at initial rotation range than at the mid and terminal rotation range of movement. This suggests better proprioceptive acuity at the initial rotation range of movement in the transverse plane. PMID- 27002664 TI - Correlates of shoulder pain in wheelchair basketball players from the Japanese national team: A cross-sectional study. AB - OBJECTIVE: To reveal correlates of shoulder pain in wheelchair basketball players from the Japanese national team. METHODS: Study participants were 19 males (29.7 +/- 5.2 years) and 21 females (29.0 +/- 8.2 years) players. We assessed shoulder pain using the wheelchair user's shoulder pain index (WUSPI). As potential correlates of shoulder pain, age, ability class, practice time and years of experience in wheelchair basketball were collected. RESULTS: The total WUSPI score for men (16.18 +/- 17.39 points) was significantly higher than that for women (8.62 +/- 15.70 points). In men, higher age was significantly correlated with greater shoulder pain for total WUSPI score and on two WUSPI items. Lower ability in wheelchair basketball was correlated with men's greater shoulder pain on three WUSPI items. In men, there were also significant correlations between longer years of experience and greater shoulder pain for total WUSPI score and on three WUSPI items. For women, there were significant correlations between longer practice time and less pain for total WUSPI score and on four WUSPI items. CONCLUSIONS: Because top male wheelchair basketball players have a higher risk of shoulder pain than female players, daily care of shoulder and periodic medical checkups are needed, especially for older male players with lower ability and more experience. PMID- 27002665 TI - Efficiency of therapeutic ultrasound on pain, disability, anxiety, depression, sleep and quality of life in patients with subacromial impingement syndrome: A randomized controlled study. AB - BACKGROUND: Subacromial impingement syndrome (SIS) is characterized by pain and disability of shoulder. Various treatment methods have been used for SIS. OBJECTIVES: The aim of our study was to evaluate efficacy of therapeutic ultrasound (US) on pain, disability, anxiety, depression, sleep quality and quality of life in patients with SIS. METHODS: Patients with SIS were randomly divided into two groups, including the group 1 (continuous US group; 3 MHz, 1.5 W/cm2, n = 26) and group 2 (sham US group, n = 24). Additionally, transcutaneous electrical nerve stimulation (TENS) + exercise program were added in both groups. Pain and disability of the shoulder were assessed by the Shoulder Pain and Disability Index (SPADI), while anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality. Quality of life was evalutaed by the Nottingham Health Profile (NHP). Patients were evaluated at baseline and after end of three weeks. RESULTS: Both groups had significantly improvements in terms of SPADI-pain, SPADI-disability, SPADI-total, NHP-pain and NHP-sleep scores after the three weeks interventions. There were significantly improvements in the Group 1 in terms of PSQI-total, and NHP-physical activity. Group 2 had significantly improvements in terms of anxiety-HADS, depression-HADS and NHP-emotional reaction scores. In the inter-group comparison, there were no significantly differences in the change scores were observed in any domains of SPADI scores, anxiety, depression and sleep scores, or any NHP scores. CONCLUSIONS: Our study showed that US does not have any benefits on SIS. TENS + exercise program are not effective on anxiety, depression and fatigue, however TENS +$ exercise program are effective on pain, disability and sleep disturbance in patients with SIS. PMID- 27002666 TI - Differences in the angle of the medial longitudinal arch and muscle activity of the abductor hallucis and tibialis anterior during sitting short-foot exercises between subjects with pes planus and subjects with neutral foot. AB - BACKGROUND AND OBJECTIVES: Excessive activity of the tibialis anterior muscle may be a causal mechanism in overuse injuries such as stress fracture in pes planus patients. However, information about this relationship is limited. In this study, we compared the angle of the medial longitudinal arch, the activities of the abductor hallucis and tibialis anterior muscles, and the activity ratio of tibialis anterior/abductor hallucis in individuals with pes planus and those with a neutral foot position during short-foot exercises conducted while sitting. METHODS: Differences between the groups were analyzed using an independent t test. In all, 28 university students participated in this study (14 subjects in each group). RESULTS: The activity of the abductor hallucis muscle was significantly lower (p < 0.001), and the activity ratio of tibialis anterior/abductor hallucis was significantly greater (p = 0.012) in the pes planus group than in the neutral foot group during the exercise. CONCLUSIONS: Clinicians should recognize that pes planus patients may compensate for reduced activation of the abductor hallucis to maintain the angle of the medial longitudinal arch during the sitting short-foot exercise. PMID- 27002667 TI - Short-term effects of upper extremity circuit resistance training on muscle strength and functional independence in patients with paraplegia. AB - BACKGROUND AND OBJECTIVES: A number of exercises to strengthen the upper extremities are recommended to increase functional independence and quality of life (QoL) in patients with paraplegia. Circuit resistance training (CRT) is a type of progressive resistive exercise performed repeatedly at fixed mechanical exercise stations. The aim of this study was to investigate the potential benefits of CRT for upper extremity muscle strength, functional independence, and QoL in patients with paraplegia. MATERIALS AND METHODS: Twenty-six patients with paraplegia who were participating in a conventional rehabilitation program at a tertiary education and research hospital were enrolled in this study. The participants were randomly assigned to two groups. The exercise group participated in the CRT program, which consisted of repetitive exercises for the upper extremities performed at fixed mechanical stations 5 sessions per week for 6 weeks, in addition to conventional rehabilitation. Participants in the control group received only conventional rehabilitation over the same period. We compared the groups with respect to QoL, as well as isokinetic muscle test outcomes in the upper extremities, using the Functional Independence Measure (FIM) and Borg's scale. RESULTS: We observed significant increases in scores on the physical component of the FIM, Borg's scale, and QoL in both the exercise and control groups. Furthermore, the large majority of isokinetic values were significantly more improved in the exercise group compared to the control group. When post treatment outcomes were compared between the groups, improvements in scores on the physical component of the FIM and in most isokinetic values were significantly greater in the exercise group. CONCLUSIONS: This study showed that CRT has positive effects on muscle strength in the upper extremities and the physical disability components of the FIM when added to conventional rehabilitation programs for paraplegic patients. However, we observed no significant improvement in QoL scores after adding CRT to a conventional treatment regime. LEVEL OF EVIDENCE: Randomized trial (Level II). PMID- 27002668 TI - Respiratory muscle endurance training reduces chronic neck pain: A pilot study. AB - BACKGROUND: Patients with chronic neck pain show also respiratory dysfunctions. OBJECTIVE: To investigate the effects of respiratory muscle endurance training (RMET) on chronic neck pain. METHODS: In this pilot study (single-subject design: 3 baseline measurements, 4 measurements during RMET), 15 neck patients (49.3 +/- 13.7 years; 13 females) conducted 20 sessions of home-based RMET using a SpiroTiger(r) (normocapnic hyperpnoea). Maximal voluntary ventilation (MVV), maximal inspiratory (Pimax) and expiratory (Pemax) pressure were measured before and after RMET. Neck flexor endurance, cervical and thoracic mobility, forward head posture, chest wall expansion and self-assessed neck disability [Neck Disability Index (NDI), Bournemouth questionnaire] were weekly assessed. Repeated measure ANOVA (Bonferroni correction) compared the first and last baseline and the last measurement after RMET. RESULTS: RMET significantly increased MVV (p= 0.025), Pimax (p= 0.001) and Pemax (p< 0.001). During RMET, neck disability significantly decreased (NDI: p= 0.001; Bournemouth questionnaire: p= 0.002), while neck flexor endurance (p< 0.001) and chest wall expansion (p< 0.001) increased. The changes in respiratory and musculoskeletal parameters did not correlate. CONCLUSIONS: RMET emerged from this pilot study as a feasible and effective therapy for reducing disability in patients with chronic neck pain. The underlying mechanisms, including blood gas analyses, need further investigation in a randomized controlled study. PMID- 27002669 TI - Reply. PMID- 27002670 TI - From the Editors. PMID- 27002671 TI - Quantitative Microbiological Risk Assessment and Source Attribution for Salmonella: Taking it Further. PMID- 27002673 TI - Assessing the Effectiveness of On-Farm and Abattoir Interventions in Reducing Pig Meat-Borne Salmonellosis within E.U. Member States. AB - As part of the evidence base for the development of national control plans for Salmonella spp. in pigs for E.U. Member States, a quantitative microbiological risk assessment was funded to support the scientific opinion required by the EC from the European Food Safety Authority. The main aim of the risk assessment was to assess the effectiveness of interventions implemented on-farm and at the abattoir in reducing human cases of pig meat-borne salmonellosis, and how the effects of these interventions may vary across E.U. Member States. Two case study Member States have been chosen to assess the effect of the interventions investigated. Reducing both breeding herd and slaughter pig prevalence were effective in achieving reductions in the number of expected human illnesses in both case study Member States. However, there is scarce evidence to suggest which specific on-farm interventions could achieve consistent reductions in either breeding herd or slaughter pig prevalence. Hypothetical reductions in feed contamination rates were important in reducing slaughter pig prevalence for the case study Member State where prevalence of infection was already low, but not for the high-prevalence case study. The most significant reductions were achieved by a 1- or 2-log decrease of Salmonella contamination of the carcass post evisceration; a 1-log decrease in average contamination produced a 90% reduction in human illness. The intervention analyses suggest that abattoir intervention may be the most effective way to reduce human exposure to Salmonella spp. However, a combined farm/abattoir approach would likely have cumulative benefits. On-farm intervention is probably most effective at the breeding-herd level for high-prevalence Member States; once infection in the breeding herd has been reduced to a low enough level, then feed and biosecurity measures would become increasingly more effective. PMID- 27002672 TI - A Quantitative Microbiological Risk Assessment for Salmonella in Pigs for the European Union. AB - A farm-to-consumption quantitative microbiological risk assessment (QMRA) for Salmonella in pigs in the European Union has been developed for the European Food Safety Authority. The primary aim of the QMRA was to assess the impact of hypothetical reductions of slaughter-pig prevalence and the impact of control measures on the risk of human Salmonella infection. A key consideration during the QMRA development was the characterization of variability between E.U. Member States (MSs), and therefore a generic MS model was developed that accounts for differences in pig production, slaughterhouse practices, and consumption patterns. To demonstrate the parameterization of the model, four case study MSs were selected that illustrate the variability in production of pork meat and products across MSs. For the case study MSs the average probability of illness was estimated to be between 1 in 100,000 and 1 in 10 million servings given consumption of one of the three product types considered (pork cuts, minced meat, and fermented ready-to-eat sausages). Further analyses of the farm-to-consumption QMRA suggest that the vast majority of human risk derives from infected pigs with a high concentration of Salmonella in their feces (>=10(4) CFU/g). Therefore, it is concluded that interventions should be focused on either decreasing the level of Salmonella in the feces of infected pigs, the introduction of a control step at the abattoir to reduce the transfer of feces to the exterior of the pig, or a control step to reduce the level of Salmonella on the carcass post-evisceration. PMID- 27002674 TI - Application of Molecular Typing Results in Source Attribution Models: The Case of Multiple Locus Variable Number Tandem Repeat Analysis (MLVA) of Salmonella Isolates Obtained from Integrated Surveillance in Denmark. AB - Salmonella is an important cause of bacterial foodborne infections in Denmark. To identify the main animal-food sources of human salmonellosis, risk managers have relied on a routine application of a microbial subtyping-based source attribution model since 1995. In 2013, multiple locus variable number tandem repeat analysis (MLVA) substituted phage typing as the subtyping method for surveillance of S. Enteritidis and S. Typhimurium isolated from animals, food, and humans in Denmark. The purpose of this study was to develop a modeling approach applying a combination of serovars, MLVA types, and antibiotic resistance profiles for the Salmonella source attribution, and assess the utility of the results for the food safety decisionmakers. Full and simplified MLVA schemes from surveillance data were tested, and model fit and consistency of results were assessed using statistical measures. We conclude that loci schemes STTR5/STTR10/STTR3 for S. Typhimurium and SE9/SE5/SE2/SE1/SE3 for S. Enteritidis can be used in microbial subtyping-based source attribution models. Based on the results, we discuss that an adjustment of the discriminatory level of the subtyping method applied often will be required to fit the purpose of the study and the available data. The issues discussed are also considered highly relevant when applying, e.g., extended multi-locus sequence typing or next-generation sequencing techniques. PMID- 27002675 TI - Erratum. PMID- 27002676 TI - Transjugular intrahepatic portosystemic shunt in refractory hydrothorax - a contribution to an unexplored indication. AB - BACKGROUND AND AIMS: Hepatic hydrothorax is a rare complication of portal hypertension, but may be potentially severe. Although conservative therapy may be effective, it is not without risk and refractory cases are not rare. The portal decompression achieved by transjugular intrahepatic portosystemic shunts (TIPS) has shown positive results in the treatment of refractory ascites, and in that sense, the analysis of their value in other complications of portal hypertension becomes relevant. The aim of this study was to evaluate the efficacy and safety of TIPS in patients with refractory hydrothorax. METHODS: This was a retrospective study including patients with refractory hydrothorax undergoing TIPS in a tertiary hospital in the period between 2000 and 2014, and evaluated the following: demographic characteristics, liver disease, and outcomes (efficacy and safety, including complications after TIPS, liver transplantation, 30-day, and 1-year mortality). RESULTS: Nineteen patients with hydrothorax underwent TIPS; most had previously undergone multiple thoracocentesis and all had hypoalbuminemia. In all, 57.9% of the patients were men, with a mean age 63+/-9 years, and 84.2% had cirrhosis of alcoholic etiology and a mean Model for End Stage Liver Disease-16, Child-Pugh B in 42.1%/Child-Pugh C in 47.4%. TIPS was effective in 73.3% of the cases. Portosystemic encephalopathy was recorded in 66.6% of the cases. Mortality was 25% at 30 days and 42.8% at 1 year with septic complications or progression of liver disease. Two patients underwent liver transplantation. The mean follow-up duration was 704 days (3-3485 days). CONCLUSION: TIPS appears to be a relatively efficient method to control hydrothorax, making it a valid option in refractory cases despite the high risk of portosystemic encephalopathy and mortality. PMID- 27002677 TI - 2015 ISSVD, ISSWSH, and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia. AB - INTRODUCTION: In 2014, the executive council of the International Society for the Study of Vulvovaginal Disease, the boards of directors of the International Society for the Study of Women's Sexual Health, and the International Pelvic Pain Society acknowledged the need to revise the current terminology of vulvar pain, on the basis of the significant increase in high-quality etiologic studies published in the last decade. MATERIALS AND METHODS: The new terminology was achieved in the following 4 steps. The first involved a terminology consensus conference with representatives of the 3 societies, held in April 2015. Then, an analysis of the relevant published studies was used to establish a level of evidence for each factor associated with vulvodynia. The terminology was amended on the basis of feedback from members of the societies. Finally, each society's board accepted the new terminology. RESULTS AND CONCLUSIONS: In 2015, the International Society for the Study of Vulvovaginal Disease, International Society for the Study of Women's Sexual Health, and International Pelvic Pain Society adopted a new vulvar pain and vulvodynia terminology that acknowledges the complexity of the clinical presentation and pathophysiology involved in vulvar pain and vulvodynia, and incorporates new information derived from evidence-based studies conducted since the last terminology published in 2003. PMID- 27002679 TI - Porphyrin-Alkaline Earth MOFs with the Highest Adsorption Capacity for Methylene Blue. AB - A series of four porphyrin-alkaline earth metal- organic frameworks [Mg(HDCPP)2 (DMF)2 ]n ?(H2 O)7 n (1), [Ca(HDCPP)2 (H2 O)2 ]n (DMF)1.5 n (2), [Sr(DCPP)(H2 O)(DMA)]n (3), and [Ba(DCPP)(H2 O)(DMA)]n (4) was isolated for the first time from solvothermal reaction between metal-free 5,15-di(4- carboxyphenyl)porphyrin (H2 DCPP) and alkaline earth ions. Single-crystal X-ray diffraction analysis reveals the 2D and 3D supramolecular network with periodic nanosized porosity for 1/2 and 3/4, respectively. The whole series of MOFs, in particular, compounds 1 and 2 with intrinsic low molecular formula weight, exhibit superior adsorption performance for methylene blue (MB) with excellent capture capacity as represented by the thus far highest adsorption amount of 952 mg g(-1) for 2 and good selectivity, opening a new way for the potential application of the main group metal-based MOFs. PMID- 27002678 TI - American Cancer Society Head and Neck Cancer Survivorship Care Guideline. AB - Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. (c) 2016 American Cancer Society. PMID- 27002680 TI - Chromogenic assay for BAY 81-8973 potency assignment has no impact on clinical outcome or monitoring in patient samples. AB - Essentials Discrepancies can exist in factor VIII activity measured by the one stage or chromogenic assays. LEOPOLD trial data were used to assess clinical impact of BAY 81-8973 potency assignment assay. Efficacy was not affected by the assay used for potency assignment and dosing of BAY 81-8973. Either assay may be used to measure factor VIII activity after BAY 81-8973 infusion. SUMMARY: Background Product-specific discrepancies have been reported for factor VIII (FVIII) activity determined with one-stage or chromogenic assays. Objective To assess the clinical impact of potency assignment of BAY 81-8973, a full-length, unmodified, recombinant human FVIII, by use of the chromogenic assay or chromogenic assay adjusted to mimic results obtained with the one-stage assay Patients/methods Patients aged 12-65 years with severe hemophilia A received BAY 81-8973 in LEOPOLD I (20-50 IU kg(-1) two or three times weekly [investigator decision]) and LEOPOLD II (randomized to 20-30 IU kg(-1) twice weekly, 30-40 IU kg(-1) three times weekly, or on-demand treatment). Both trials included two 6 month crossover periods in which potency labeling was determined with the chromogenic substrate assay as per the European Pharmacopoeia (CS/EP) or the chromogenic substrate assay adjusted to mimic results obtained with the one-stage assay (CS/ADJ). The annualized bleeding rate (ABR) and FVIII incremental recovery were assessed by the use of pooled data. Results The analysis was perfomed on 121 patients. Median (quartile [Q] 1; Q3) ABRs during the CS/EP and CS/ADJ periods were 1.98 (0; 5.92) and 1.98 (0; 7.34), respectively. The mean incremental recovery was > 2 IU dL(-1) per IU kg(-1) in both periods with the use of either assay for postinfusion FVIII measurements. The median (Q1; Q3) chromogenic/one stage assay recovery ratio was 1.054 (0.892; 1.150) for the CS/EP period when a plasma standard was used for calibration. Conclusions No impact on the ABR was observed with chromogenic-based as compared with one-stage assay-based potency and dosing. Either assay may be used to determine FVIII plasma activity after infusion of BAY 81-8973 without the need for a product-specific standard. PMID- 27002681 TI - Health impact of catch-up growth in low-birth weight infants: systematic review, evidence appraisal, and meta-analysis. AB - This study aimed to systematically review and appraise evidence on the short-term (e.g. morbidity, mortality) and long-term (obesity and non-communicable diseases, NCDs) health consequences of catch-up growth (vs. no catch-up growth) in individuals with a history of low birth weight (LBW).We searched MEDLINE, EMBASE, Global Health, CINAHL plus, Cochrane Library, ProQuest Dissertations and Thesis and reference lists. Study quality was assessed using the risk of bias assessment tool from the Agency for Health Care Research and Quality, and the evidence base was assessed using the GRADE tool. Eight studies in seven cohorts (two from high income countries, five from low-middle-income countries) met the inclusion criteria for short-term (mean age: 13.4 months) and/or longer-term (mean age: 11.1 years) health outcomes of catch-up growth, which had occurred by 24 or 59 months. Of five studies on short-term health outcomes, three found positive associations between weight catch-up growth and body mass and/or glucose metabolism; one suggested reduced risk of hospitalisation and mortality with catch-up growth. Three studies on longer-term health outcomes found catch-up growth were associated with higher body mass, BMI or cholesterol. GRADE assessment suggested that evidence quantity and quality were low. Catch-up growth following LBW may have benefits for the individual with LBW in the short term, and may have adverse population health impacts in the long-term, but the evidence is limited. Future cohort studies could address the question of the consequences of catch-up growth following LBW more convincingly, with a view to informing future prevention of obesity and NCDs. (c) 2016 John Wiley & Sons Ltd. PMID- 27002682 TI - Na+ and solute diffusion in aqueous channels of Myverol bicontinuous cubic phase: PGSE NMR and computer modelling. AB - The apparent diffusion coefficients of 23 Na+ ions and the solute 2 fluoroethylamine present in the aqueous domain of a Myverol/water bulk bicontinuous cubic phase (BCP) were measured using pulsed field-gradient spin echo (PGSE) NMR spectroscopy. The measured values were dependent on the diffusion time interval, which is a characteristic of restricted diffusion. The translational motion of 23 Na+ and water in the aqueous channels of a cubic phase were simulated using a Monte-Carlo random walk algorithm, and the simulation results were compared with those from real PGSE NMR experiments. The simulations indicated that diffusion of 23 Na+ ions and water would appear to be restricted even on the shortest timescales available to PGSE NMR experiments. The micro viscosity of the aqueous domain of the BCPs was estimated from the longitudinal relaxation times of 23 Na+ and 2-fluoroethylamine; this was three times higher than in free solution and suggests one of (but not the only) likely impediments to the release of hydrophilic drugs from stabilised aqueous dispersions of BCPs (cubosomes) when they are used therapeutically in vivo. Monte Carlo simulations of diffusive efflux from cubosomes suggest that the principal impediment to drug release is presented by a surfactant or lipid barrier at the cubosome surface, which separates the BCP aqueous channels from the bulk solution. The dynamics inferred from these studies informs quantitative predictions of drug delivery from cubosomes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27002683 TI - D-A1-D-A2 Copolymer Based on Pyridine-Capped Diketopyrrolopyrrole with Fluorinated Benzothiadiazole for High-Performance Ambipolar Organic Thin-Film Transistors. AB - A novel donor-acceptor-donor-acceptor (D-A1-D-A2) pi-conjugated copolymer (PDBPyDT2FBT) has been prepared by Stille coupling reaction. It is found that PDBPyDT2FBT exhibits low LUMO energy level mainly because of multiple electron deficient units and donor-acceptor interaction, which is favorable to obtain more efficient electron injection and transport in organic thin-film transistors (OTFTs). Moreover, introducing two electron-deficient moieties into the thiophene containing copolymer increases the length of conjugated main chain and enhances the coplanarity of the backbone, which may be beneficial for promoting the molecular crystallinity and improving molecular ordering capability at low temperatures. High electron and hole mobilities up to 0.65 and 0.24 cm(2) V(-1) s(-1) were obtained at relatively low annealing temperatures of 100 and 80 degrees C, respectively, implying that PDBPyDT2FBT is a promising ambipolar polymer semiconductor applied in low-cost and large-area manufacturing of OTFTs. PMID- 27002684 TI - Contrasting changes in the abundance and diversity of North American bird assemblages from 1971 to 2010. AB - Although it is generally recognized that global biodiversity is declining, few studies have examined long-term changes in multiple biodiversity dimensions simultaneously. In this study, we quantified and compared temporal changes in the abundance, taxonomic diversity, functional diversity, and phylogenetic diversity of bird assemblages, using roadside monitoring data of the North American Breeding Bird Survey from 1971 to 2010. We calculated 12 abundance and diversity metrics based on 5-year average abundances of 519 species for each of 768 monitoring routes. We did this for all bird species together as well as for four subgroups based on breeding habitat affinity (grassland, woodland, wetland, and shrubland breeders). The majority of the biodiversity metrics increased or remained constant over the study period, whereas the overall abundance of birds showed a pronounced decrease, primarily driven by declines of the most abundant species. These results highlight how stable or even increasing metrics of taxonomic, functional, or phylogenetic diversity may occur in parallel with substantial losses of individuals. We further found that patterns of change differed among the species subgroups, with both abundance and diversity increasing for woodland birds and decreasing for grassland breeders. The contrasting changes between abundance and diversity and among the breeding habitat groups underscore the relevance of a multifaceted approach to measuring biodiversity change. Our findings further stress the importance of monitoring the overall abundance of individuals in addition to metrics of taxonomic, functional, or phylogenetic diversity, thus confirming the importance of population abundance as an essential biodiversity variable. PMID- 27002685 TI - Simultaneous Tunable Selection and Self-Assembly of Si Nanowires from Heterogeneous Feedstock. AB - Semiconducting nanowires (NWs) are becoming essential nanobuilding blocks for advanced devices from sensors to energy harvesters, however their full technology penetration requires large scale materials synthesis together with efficient NW assembly methods. We demonstrate a scalable one-step solution process for the direct selection, collection, and ordered assembly of silicon NWs with desired electrical properties from a poly disperse collection of NWs obtained from a supercritical fluid-liquid-solid growth process. Dielectrophoresis (DEP) combined with impedance spectroscopy provides a selection mechanism at high signal frequencies (>500 kHz) to isolate NWs with the highest conductivity and lowest defect density. The technique allows simultaneous control of five key parameters in NW assembly: selection of electrical properties, control of NW length, placement in predefined electrode areas, highly preferential orientation along the device channel, and control of NWs deposition density from few to hundreds per device. Direct correlation between DEP signal frequency and deposited NWs conductivity is confirmed by field-effect transistor and conducting AFM data. Fabricated NW transistor devices demonstrate excellent performance with up to 1.6 mA current, 10(6)-10(7) on/off ratio and hole mobility of 50 cm(2) V(-1) s(-1). PMID- 27002686 TI - Control by reinforcers across time and space: A review of recent choice research. AB - Reinforcers affect behavior. A fundamental assumption has been that reinforcers strengthen the behavior they follow, and that this strengthening may be context specific (stimulus control). Less frequently discussed, but just as evident, is the observation that reinforcers have discriminative properties that also guide behavior. We review findings from recent research that approaches choice using nontraditional procedures, with a particular focus on how choice is affected by reinforcers, by time since reinforcers, and by recent sequences of reinforcers. We also discuss how conclusions about these results are impacted by the choice of measurement level and display. Clearly, reinforcers as traditionally considered are conditionally phylogenetically important to animals. However, their effects on behavior may be solely discriminative, and contingent reinforcers may not strengthen behavior. Rather, phylogenetically important stimuli constitute a part of a correlated compound stimulus context consisting of stimuli arising from the organism, from behavior, and from physiologically detected environmental stimuli. Thus, the three-term contingency may be seen, along with organismic state, as a correlation of stimuli. We suggest that organisms may be seen as natural stimulus correlation detectors so that behavioral change affects the overall correlation and directs the organism toward currently appetitive goals and away from potential aversive goals. As a general conclusion, both historical and recent choice research supports the idea that stimulus control, not reinforcer control, may be fundamental. PMID- 27002687 TI - Behavioral variability in an evolutionary theory of behavior dynamics. AB - McDowell's evolutionary theory of behavior dynamics (McDowell, 2004) instantiates populations of behaviors (abstractly represented by integers) that evolve under the selection pressure of the environment in the form of positive reinforcement. Each generation gives rise to the next via low-level Darwinian processes of selection, recombination, and mutation. The emergent patterns can be analyzed and compared to those produced by biological organisms. The purpose of this project was to explore the effects of high mutation rates on behavioral variability in environments that arranged different reinforcer rates and magnitudes. Behavioral variability increased with the rate of mutation. High reinforcer rates and magnitudes reduced these effects; low reinforcer rates and magnitudes augmented them. These results are in agreement with live-organism research on behavioral variability. Various combinations of mutation rates, reinforcer rates, and reinforcer magnitudes produced similar high-level outcomes (equifinality). These findings suggest that the independent variables that describe an experimental condition interact; that is, they do not influence behavior independently. These conclusions have implications for the interpretation of high levels of variability, mathematical undermatching, and the matching theory. The last part of the discussion centers on a potential biological counterpart for the rate of mutation, namely spontaneous fluctuations in the brain's default mode network. PMID- 27002688 TI - Choice in transition: Replication and extension to preschool children in a naturalistic setting. AB - This study replicated previous basic research into the dynamics of choice and extended this analysis to children's behavior in a naturalistic setting. Two preschoolers with disabilities were observed interacting with their teachers at baseline and during an experimental analysis involving four pairs of concurrent variable-interval schedules of adult attention implemented by an experimenter. Each child was exposed to four experimental phases in which the relative reinforcer rates for on- and off-task behavior were 10:1, 1:1, 1:10, and reversed back to 10:1. The 10:1 phase was designed to mimic the same schedules and types of adult attention observed at baseline. We used the generalized matching equation to model steady-state behavior at the end of the transition phases and to evaluate changes in sensitivity at various points throughout the phases. Choice in transition was evaluated by plotting log behavior ratios by session, cumulated time on- and off-task and cumulated attention for on- and off-task behavior by session, and interreinforcer behavior ratios following different sequences of the first four reinforcer deliveries. The generalized matching equation accounted for a large proportion of variance in steady-state responding, sensitivity values increased steadily throughout the phases, patterns of choice in transition were similar to those reported in basic research, and interreinforcer preference generally shifted toward the just-reinforced alternative. These findings are consistent with previous basic research and support the generality of the dynamics of choice to children's on- and off-task behavior reinforced by adult attention. PMID- 27002689 TI - Large Porous Particles for Sustained Release of a Decoy Oligonucelotide and Poly(ethylenimine): Potential for Combined Therapy of Chronic Pseudomonas aeruginosa Lung Infections. AB - We have recently demonstrated that the specific inhibition of nuclear factor kappaB by a decoy oligonucleotide (dec-ODN) delivered through inhalable large porous particles (LPP) made of poly(lactic-co-glycolic acid) (PLGA) may be highly beneficial for long-term treatment of lung inflammation. Nevertheless, besides chronic inflammation, multifunctional systems aimed to control also infection are required in chronic lung diseases, such as cystic fibrosis (CF). In this work, we tested the hypothesis that engineering PLGA-based LPP with branched poly(ethylenimine) (PEI) may improve LPP properties for pulmonary delivery of dec ODN, with particular regard to the treatment of Pseudomonas aeruginosa lung infections. After getting insight into the role of PEI on the technological properties of PLGA-based LPP for delivery of dec-ODN, the putative synergistic effect of PEI free or PEI released from LPP on in vitro antimicrobial activity of tobramycin (Tb) and aztreonam (AZT) against P. aeruginosa was elucidated. Meanwhile, cytotoxicity studies on A549 cells were carried out. Results clearly demonstrate that the dry powders have promising aerosolization properties and afford a prolonged in vitro release of both dec-ODN and PEI. The encapsulation of PEI into LPP results in a 2-fold reduction of the minimum inhibitory concentration of AZT, while reducing the cytotoxic effect of PEI. Of note, the developed ODN/PLGA/PEI LPP persisted at lung at least for 14 days after intratracheal administration in rats where they can provide sustained and combined release of dec-ODN and PEI. dec-ODN will likely act as an anti inflammatory drug, while PEI may enhance the therapeutic activity of inhaled antibiotics, which are commonly employed for the treatment of concomitant lung infections. PMID- 27002690 TI - Structuralization of Ca(2+)-Based Metal-Organic Frameworks Prepared via Coordination Replication of Calcium Carbonate. AB - The emergence of metal-organic frameworks (MOFs) as potential candidates to supplant existing adsorbent types in real-world applications has led to an explosive growth in the number of compounds available to researchers, as well as in the diversity of the metal salts and organic linkers from which they are derived. In this context, the use of carbonate-based precursors as metal sources is of interest due to their abundance in mineral deposits and their reaction chemistry with acids, resulting in just water and carbon dioxide as side products. Here, we have explored the use of calcium carbonate as a metal source and demonstrate its versatility as a precursor to several known frameworks, as well as a new flexible compound based on the 2,5-dihydroxybenzoquinone (H2dhbq) linker, Ca(dhbq)(H2O)2. Furthermore, inspired by the ubiquity and unique structures of biomineralized forms of calcium carbonate, we also present examples of the preparation of superstructures of Ca-based MOFs via the coordination replication technique. In all, the results confirm the suitability of carbonate based metal sources for the preparation of MOFs and further expand upon the growing scope of coordination replication as a convenient strategy for the preparation of structuralized materials. PMID- 27002691 TI - Expedient Synthesis of Furo[2,3-d][1,3]thiazinamines and Pyrano[2,3 d][1,3]thiazinamines from Enones and Thiourea. AB - Michael addition of thiourea to enones with subsequent intramolecular aminal ether formation provided easy access to furo[2,3-d]thiazinamines and pyrano[2,3 d][1,3]thiazin-2-amines. These amines served as versatile intermediates to a variety of beta-amyloid cleaving enzyme-1 (BACE1) inhibitors. PMID- 27002692 TI - Rhodium-Catalyzed Cycloisomerization of 2-Silylethynyl Phenols and Anilines via 1,2-Silicon Migration. AB - It has been established that a cationic rhodium(I)/BINAP complex catalyzes the cycloisomerization of 2-silylethynylphenols, leading to 3-silylbenzofurans, via 1,2-silicon migration. Similarly, the cycloisomerization of 2 silylethynylanilines, leading to 3-silylindoles, via 1,2-silicon migration was catalyzed by a cationic rhodium(I)/H8-BINAP complex. PMID- 27002693 TI - Concurrent Validity of GPS for Deriving Mechanical Properties of Sprint Acceleration. AB - PURPOSE: To test the concurrent validity of data from 2 different global positioning system (GPS) units for obtaining mechanical properties during sprint acceleration using a field method recently validated by Samozino et al. METHODS: Thirty-two athletes performed maximal straight-line sprints, and their running speed was simultaneously measured by GPS units (sampling rate: 20 or 5 Hz) and either a radar or laser device (devices taken as references). Lower-limb mechanical properties of sprint acceleration (theoretical maximal force, theoretical maximal speed, maximal power) were derived from a modeling of the speed-time curves using an exponential function in both measurements. Comparisons of mechanical properties from 20- and 5-Hz GPS units with those from reference devices were performed for 80 and 62 trials, respectively. RESULTS: The percentage bias showed a wide range of overestimation or underestimation for both systems (-7.9% to 9.7% and -5.1% to 2.9% for 20- and 5-Hz GPS), while the ranges of its 90% confidence limits for 20-Hz GPS were markedly smaller than those for 5 Hz GPS. These results were supported by the correlation analyses. CONCLUSIONS: Overall, the concurrent validity for all variables derived from 20-Hz GPS measurements was better than that obtained from the 5-Hz GPS units. However, in the current state of GPS devices' accuracy for speed-time measurements over a maximal sprint acceleration, it is recommended that radar, laser devices, and timing gates remain the reference methods for implementing the computations of Samozino et al. PMID- 27002694 TI - [Comparative study bone tissue temperature changes by using conventional and piezosurgical methods in dental implantology]. AB - The laboratory study compared thermal bone lesion by the formation of dental implant bed using traditional and piezosurgical method with varying degrees of irrigation. The study was carried out on cadaveric mandible and porcine mandible with preserved soft tissues. Implant bed was formed by Implantmed dispenser (W&H, Austria) and AstraTech drills (Sweden) according to standard clinical protocol or by piezosurgical device Implant Center (Satelec Acteon Group, France) with Intra Lift II (Satelec Acteon Group, Frantsiya) and No1 scalpel tips with D1 power under minimal and maximal irrigation. The results showed that the formation of the bone bed was safe when using both conventional and piezosurgical method under copious irrigation. The possibility of bone tissue thermal damage increases when using minimum irrigation or no irrigation. PMID- 27002695 TI - [Physiological changes in the morphology of the main structural enamel unit - hydroxyapatite crystal - during its life span (in vitro study)]. AB - The in vitro study by means of complex laboratory techniques including X-ray faze analysis, infrared spectroscopy, scanning electron and atomic force microscopy defined age-related physiological mineralization process as a shift of the structural enamel unit - nanocrystalline hydroxyapatite crystals - TO microcrystal phase. Relevant anatomical sites with age-dependent enamel optical characteristics corresponding to certain ratio of hydroxyapatite phases and the compliance of their color characteristics to composites enamel layers were revealed. PMID- 27002696 TI - [Optimization of complex treatment of patients with severe oral leukoplakia]. AB - The aim of the study was to prove the rationale for antiviral therapy combined with surgical procedures for treatment of severe oral leukoplakia. Complex clinical and laboratory evaluation and treatment was performed in 56 patients divided in 2 groups. Control group was presented by 13 patients receiving dental treatment, local and systemic keratoplastic formulations. Main group involved 43 patients in which conventional treatment protocol was completed by antiviral therapy and surgical procedures. Leukoplakia diagnosis was based on clinical findings, histological and immunohistochemical studies as well as optic coherent tomography data. The obtained results evidently prove the necessity for including antiviral therapy and surgical procedures in treatment scheme of severe oral leukoplakia. PMID- 27002697 TI - [Remineralizing effectiveness of desensitizing toothpastes in the prevention of dental diseases among workers with harmful working conditions]. AB - The study of desensitizing and remineralizing effect of Sensodyn series toothpastes among 407 medical workers with harmful industrial factors was carried out. It was revealed that harmful working conditions contributed to the development of teeth hard tissues pathology of carious and non-carious origin. The investigated toothpastes eliminate hypersensitivity, stabilize the processes of demineralization and normalize the remineralization processes. PMID- 27002698 TI - [Social and hygienic aspects of mandible fractures in Republic of Sakha (Yakutia)]. AB - Comprehensive social and hygienic survey of 209 patients with mandible fracture was conducted. Their social features were: young adults, predominantly male, ethnicity mainly yakuts, temporarily unemployed, with secondary and post secondary education and health behavior problems. The majority of jaw injuries were caused by household (26.21 +/- 0.92%) and street traumas (63.03 +/- 0.46%). High prevalence of major oral diseases depends strongly on the low sanitary culture, which had a negative impact on the development of posttraumatic complications. PMID- 27002699 TI - [Features of the hormonal status in patients with temporomandibular joint dysfunction and class II malocclusion]. AB - The article presents data on androgen levels in female patients with temporomandibular joint (TMJ) dysfunction of varying degree and class II malocclusion. The study revealed significant correlation between degenerative and inflammatory TMJ changes and androgens level in patients with stigmas of connective tissue dysplasia (p<0.05), probably due to indirect proinflammatory action of androgens as they stimulate inflammatory mediators expression. PMID- 27002700 TI - [The effect of orthodontic treatment on the change of oropharynx features in patients with dentoalveolar anomalies and nasopharyngeal tonsil hypertrophy]. AB - The paper presents the results of comprehensive survey and orthodontic treatment of 40 children with dentoalveolar anomalies and nasopharyngeal tonsil hypertrophy aged 7-9 years. The linear parameters obtained by cone beam CT and TWH in the lateral projection were analyzed. The study revealed changes, indicating that the presence of nasopharyngeal tonsil hypertrophy, leads to pathology of the dental system and estimated the efficiency of muscle training and combined use of functional devices and elastopositioner "Corrector" for the treatment of anomalies of dentition and the formation of physiological occlusion in the process of permanent teeth eruption. PMID- 27002701 TI - [Juvenile paradental cysts in children after mandible distraction: case-control study and clinical cases presentation]. AB - Seventy-five children aged 6-17 years (mean age 9.8+/-4.1 years) that received mandible distraction (MD) at the age of 0-17 years (mean age at MD 6.1+/-4.3) were included in the study. Indication for MD were hemifacial microsomia (n=41), Goldenhar syndrome (n=4), Robin sequence (n=10), Treacher, Collins syndrome (n=7) or acquired mandible underdevelopment (n=13). Control groups consisted of 22 children aged 5-14 years (mean age 7.0+/-3.7 years) with mandible underdevelopment of similar origin (hemifacial microsomia (n=15), Goldenhar syndrome (n=2), Robin sequence (n=4), Treacher, Collins syndrome (n=1)) with no history of MD and 80 healthy children aged 6-10 years (mean age 7.1+/-2.2 years). Case-control study results proved MD to be the risk factor for juvenile paradental cysts (JPCs) with the risk more prominent in early MD cases. JPCs often do not manifest clinically and may resolve spontaneously but in refractory cases lesion curettage without endodontic treatment is an adequate approach, as JPCs are usually not associated with pulp necrosis. PMID- 27002702 TI - [The study of caries incidence in children according to WHO Significant Index of Caries]. AB - The dental hard tissues state was evaluated by SIC index according to a survey of the 5-16-year-old children from Lviv. The highest SIC index of the primary teeth was estimated in children of 6 years old (9.91+/-0.40) and the highest mean of the SIC index of the permanent teeth (9.40+/-0.36) was estimated in 16-year-old children. It was established that SIC of the permanent teeth in children of 6-9 years old is higher than the average caries intensity in 2.1-2.94 times, indicating the need for a more thorough approach to cariespreventive work among schoolchildren of this age. PMID- 27002703 TI - Perceived stress and anhedonia predict short-and long-term weight change, respectively, in healthy adults. AB - OBJECTIVE: Perceived stress; emotional eating; anhedonia; depression and dietary restraint, hunger, and disinhibition have been studied as risk factors for obesity. However, the majority of studies have been cross-sectional and the directionality of these relationships remains unclear. In this longitudinal study, we assess their impact on future weight change. METHODS: Psychological predictors of weight change in short- (6month) and long-term (>1year) periods were studied in 65 lean and obese individuals in two cohorts. Subjects participated in studies of food intake and metabolism that did not include any type of medication or weight loss interventions. They completed psychological questionnaires at baseline and weight change was monitored at follow-up visits. RESULTS: At six months, perceived stress predicted weight gain (r(2)=0.23, P=0.02). There was a significant interaction (r(2)=.38, P=0.009) between perceived stress and positive emotional eating, such that higher scores in both predicted greater weight gain, while those with low stress but high emotional eating scores lost weight. For long-term, higher anhedonia scores predicted weight gain (r(2)=0.24, P=0.04). Depression moderated these effects such that higher scores in both predicted weight gain but higher depression and lower anhedonia scores predicted weight loss. CONCLUSION: There are different behavioral determinants for short- and long-term weight change. Targeting perceived stress may help with short-term weight loss while depression and anhedonia may be better targets for long-term weight regulation. PMID- 27002705 TI - [Journal Sportverletzung Sportschaden--Quo vadis 2016?]. PMID- 27002704 TI - Environmental enrichment rescues the effects of early life inflammation on markers of synaptic transmission and plasticity. AB - Environmental enrichment (EE) has been successful at rescuing the brain from a variety of early-life psychogenic stressors. However, its ability to reverse the behavioral and neural alterations induced by a prenatal maternal infection model of schizophrenia is less clear. Moreover, the specific interactions between the components (i.e. social enhancement, novelty, physical activity) of EE that lead to its success as a supportive intervention have not been adequately identified. In the current study, standard housed female Sprague-Dawley rats were administered either the inflammatory endotoxin lipopolysaccharide (LPS; 100MUg/kg) or pyrogen-free saline (equivolume) on gestational day 15. On postnatal day 50, offspring were randomized into one of three conditions: EE (group housed in a large multi-level cage with novel toys, tubes and ramps), Colony Nesting (CN; socially-housed in a larger style cage), or Standard Care (SC; pair-housed in standard cages). Six weeks later we scored social engagement and performance in the object-in-place task. Afterwards hippocampus and prefrontal cortex (n=7-9) were collected and evaluated for excitatory amino acid transporter (EAAT) 1-3, brain-derived neurotrophic factor (BDNF), and neurotrophic tyrosine kinase, receptor type 2 (TrkB) gene expression (normalized to GAPDH) using qPCR methods. Overall, we show that gestational inflammation downregulates genes critical to synaptic transmission and plasticity, which may underlie the pathogenesis of neurodevelopmental disorders such as schizophrenia and autism. Additionally, we observed disruptions in both social engagement and spatial discrimination. Importantly, behavioral and neurophysiological effects were rescued in an experience dependent manner. Given the evidence that schizophrenia and autism may be associated with infection during pregnancy, these data have compelling implications for the prevention and reversibility of the consequences that follow immune activation in early in life. PMID- 27002706 TI - [Effects of Complex Versus Block Strength Training on the Athletic Performance of Elite Youth Soccer Players]. AB - BACKGROUND: Muscle strength and speed are important determinants of soccer performance. It has previously been shown that complex training (CT, combination of strength and plyometric exercises within a single training session) is effective to enhance strength and speed performance in athletes. However, it is unresolved whether CT is more effective than conventional strength training that is delivered in one single block (BT) to increase proxies of athletic performance. Thus, the aim of the present study was to investigate the effects of CT versus BT on measures of muscle strength/power, speed, and agility in elite youth soccer players. METHODS: Eighteen male elite youth soccer players conducted six weeks (2 sessions/week, 30 min. each) of progressive CT (n = 10, age: 18.5 +/ 2.2 years) or BT (n = 8, age: 18.1 +/- 1.6 years) in addition to their regular soccer training (approx. 6 sessions/week, 60-90 min. each). Before and after training, tests were conducted for the assessment of strength (one-repetition maximum [1RM] squat), power (countermovement jump [CMJ]), speed (30-m linear sprint), and agility (T test). Non-parametric analyses were used to calculate differences within (Wilcoxon test) and between (Mann-Whitney-U test) groups. RESULTS: Both CT and BT proved to be safe (i.e. no training-related, but six match-related injuries reported) and feasible (i.e. attendance rate of >= 80% in both groups) training regimens when implemented in addition to regular soccer training. The statistical analysis revealed significant improvements from pre training to post-training tests for the CT group in 1 RM squat (p = 0.043) and CMJ height (p = 0.046). For the BT-group, significantly enhanced sprint times were observed over 5 m (p = 0.039) and 10 m (p = 0.026). Furthermore, both groups significantly improved their t test time (CT: p = 0.046; BT: p = 0.027). However, group comparisons (CT vs. BT) over time (post-training minus pre-training test) did not show any significant differences. CONCLUSION: Six weeks of CT and BT resulted in significant improvements in proxies of athletic performance. Yet CT did not produce any additional effects compared to BT. Future research is needed to examine whether the observed test-specific changes, i.e. improvements in strength/power for the CT-group and improvements in speed for the BT-group, are due to the applied configuration of strength, plyometric, and sprint exercises or if they rather indicate a general training response. PMID- 27002707 TI - [Interdisciplinary Assessment Criteria for Rehabilitation after Injuries of the Lower Extremity: A Function-Based Return to Activity Algorithm]. AB - BACKGROUND: In the treatment of patients with lower extremity injuries, a paradigm shift is taking place: Time-dependent concepts are increasingly being replaced by function-based concepts. METHODS: A function-based Return to Activity Algorithm is presented which contains a level classification (I-IV). Qualitative and subsequent quantitative tests are assigned to every level. Within each level, first the respective qualitative test has to be passed before patients are allowed to perform the corresponding quantitative test. Criteria for success are qualitative and quantitative comparisons with the unaffected side. Before entering the next level, both tests have to be successfully passed. The levels are ordered according to increasing demands on the loco-motor system. These demands are adequate stability without impact interaction in sagittal plane for level I, followed by dynamic stability demands for level II. Impacts in frontal plane are added for level III and finally multidirectional impacts have to be compensated at level IV. The time expenditure per level is no more than five minutes. The case of a professional soccer player will serve to exemplify the Return to Activity Algorithm. Following a knee injury, he underwent arthroscopy with ACL reconstruction (patellar tendon) and a partial meniscectomy (lateral and medial). RESULTS: The athlete was able to successfully pass each level and finished his rehabilitation 203 days post injury. He returned to the team training 221 days post injury. 247 days post injury, the athlete completed his first game. CONCLUSION: The Return to Activity Algorithm is able to support the evaluation of the functional status of the loco-motor system after injury or surgery and is furthermore capable of uncovering deficits or asymmetries, which are a proven risk for re-injury. This function-oriented individual approach is able to adequately dose the therapeutic efforts on an individual basis. With this approach, the right timing for a safe return to sports activities can be detected with high certainty. PMID- 27002708 TI - [Injury of the Obturator Internus Muscle--a Rare Differential Diagnosis in a Soccer Player]. AB - BACKGROUND: Lesions/irritations of the obturator internus muscle (OIM) are rare, several differential diagnoses are possible. PATIENT: This paper describes the case of an OIM injury in a professional football player. RESULTS: On clinical examination, painful internal rotation of the hip joint was an indication for a lesion/irritation of the OIM. MRI was the procedure of choice for imaging. Movement analysis served to detect a functional malposition. CONCLUSION: A short recovery time requires functional treatment as well as the use of orthopaedic aids to correct possible deformities. PMID- 27002709 TI - Sapovirus prevalence in children less than five years of age hospitalised for diarrhoeal disease in South Africa, 2009-2013. AB - BACKGROUND: Although sapovirus (SaV) has been detected in 2.2-12.7% of gastroenteritis cases globally, there are limited data on SaV epidemiology. OBJECTIVES: Describe the epidemiology, clinical characteristics and factors associated with SaV gastroenteritis in hospitalised children <5 years of age in South Africa. STUDY DESIGN: Between 2009 and 2013 during prospective diarrhoeal surveillance, stool specimens were collected from four sites and screened for SaVs and associated enteric pathogens using ELISA, microscopy, conventional and real-time PCR. Epidemiological and clinical data were compared in patients with or without SaV. Odds ratios were assessed by bivariate and stepwise multivariable logistic regression analysis. RESULTS: Sapoviruses were detected in 7.7% (238/3103) of children admitted to hospital and 11.4% (9/79) of deaths. Sapovirus was detected more commonly in children 19-24 months compared to<6months (aOR=2.3; p=0.018) and in males (aOR=2.0; p=0.001). Additional factors associated with SaV detection included residing with>=7 inhabitants compared to <=3 (aOR=2.2; p=0.011) and concomitant norovirus infections (aOR=3.0; p=0.003). HIV-infected children with SaV were more likely to have bloody stools (aOR=16.8; p<0.001), low birth weight (<2.5kg; aOR=5.8; p=0.007) and live in environments without flush toilets (aOR=8.1; p=0.003) compared to HIV-uninfected children. CONCLUSIONS: Sapoviruses, which are perceived to cause mild diarrhoea, were detected in hospitalised children and diarrhoeal deaths in South Africa. Determinants increasing the odds of SaV included overcrowding and concomitant infections while HIV-infected children with SaV displayed bloody stools, low birth weight and reduced access to proper sanitation. Mitigation strategies against SaV infections include improved sanitation. PMID- 27002710 TI - Sourcing of the WHO human papillomavirus type 18 international standards for HPV antibody levels. AB - BACKGROUND: HPV serology is important for studies of vaccine immunogenicity, but can not be performed in a comparable manner without international standardisation. OBJECTIVES: To find suitable candidate sera from naturally infected persons for use as International Standards (IS) for antibodies to high risk HPVs, with priority for HPV-18. STUDY DESIGN: 946 healthy Thai women (median age 44, range 18-83) and 61 cervical cancer patients were screened using an HPV pseudovirion-Luminex assay to detect antibodies to genital (HPV-6,-11,-16,-18, 31,-33,-45,-52,-58,-68) and non-genital HPV types (HPV-5,-15,-32,-38 and -76). Suitable candidate sera should ideally be mono-specific (have reactivity against only one genital HPV) and have high antibody levels that are stable over time. RESULTS: Seroprevalences of HPV-16,-31,-52 and -58 were at least twice as high among cancer patients compared to healthy individuals. Thirteen healthy women who met the IS inclusion criteria in initial testing also consented to blood-bag donations. Donations from 2 women with high HPV-18 Ab titers were pooled to the HPV-18 candidate IS, later established as the WHO official IS for HPV antibodies. Sera that could potentially be used as candidate IS for other oncogenic HPVs have also been identified. CONCLUSIONS: In the Thai population, seroepidemiology implicated HPV types HPV-16,-31,-52 and -58 as particularly associated with cervical cancer. A well characterized cohort study has allowed sourcing of materials for an IS for HPV-18 antibodies and could conceivably be used for IS for other HPV types as well. PMID- 27002711 TI - Theoretical Analysis of a Self-Replicator With Reduced Template Inhibition Based on an Informational Leaving Group. AB - The first non-enzymatic self-replicating systems, as proposed by von Kiedrowski (Angew Chem Int Ed Engl 25(10):932-935, 1986) and Orgel (Nature 327(6120):346 347, 1987), gave rise to the analytical background still used today to describe artificial replicators. What separates a self-replicating from an autocatalytic system is the ability to pass on structural information (Orgel, Nature 358(6383):203-209, 1992). Utilising molecular information, nucleic acids were the first choice as prototypical examples. But early self-replicators showed parabolic over exponential growth due to the strongly bound template duplex after template-directed ligation of substrates. We propose a self-replicating scheme with a weakly bound template duplex, using an informational leaving group. Such a scheme is inspired by the role of tRNA as leaving group and information carrier during protein synthesis, and is based on our previous experience with nucleotide chemistry. We analyse theoretically this scheme and compare it to the classical minimal replicator model. We show that for an example hexanucleotide template mirroring that is used by von Kiedrowski (Bioorganic chemistry frontiers, 1993) for the analysis of the classical minimal replicator, the proposed scheme is expected to result in higher template self-replication rate. The proposed self replicating scheme based on an informational leaving group is expected to outperform the classical minimal replicator because of a weaker template duplex bonding, resulting in reduced template inhibition. PMID- 27002713 TI - Granulocyte colony-stimulating factor (G-CSF) increases histone-complexed DNA plasma levels in healthy volunteers. AB - Granulocyte colony-stimulating factor (G-CSF) is an activator of neutrophil granulocytes. Neutrophil extracellular traps are a defensive mechanism consisting of neutrophils, platelets, DNA, histones and antimicrobial proteins. This study was performed to determine whether G-CSF increases histone-complexed DNA in the plasma of healthy volunteers. In total, 51 healthy volunteers (25 males and 26 females) were treated with G-CSF (18 with 300 ug single dose i.v., 27 with 5 ug/kg s.c. for 4 days) and six participants received a placebo. Histone-complexed DNA was measured by enzyme immunoassay in plasma samples at predefined time points (0, 2, 4, 6, 24 h after single dose, day 1, day 2 and day 5 after repeated doses). Histone levels were quantified by Western blotting. A single dose of G CSF rapidly increased hc-DNA by about 50 % (p < 0.05 for 2-24 h). After repeated doses the increase was even more pronounced: hc-DNA increased by about 50 % (3.0 +/- 0.9, p < 0.001 after 24 h and about fourfold after 96 h (p < 0.001)). A statistical significant increase in histone levels was detected as early as 4 h after G-CSF injection (0.43 +/- 0.2 vs. 1.08 +/- 0.3 ug/ml; p = 0.034). In the placebo group no significant changes occurred. Moreover, significantly higher levels of hc-DNA were measured in male compared to female subjects (226 +/- 43 vs. 84 +/- 19, p < 0.001). G-CSF injection substantially increases hc-DNA levels in healthy volunteers. There is a significant gender difference in hc-DNA at the baseline. PMID- 27002714 TI - Clinical value and pitfalls of fluorescent cholangiography during single-incision laparoscopic cholecystectomy. AB - PURPOSE: To clarify the clinical value and pitfalls of fluorescent cholangiography (FC) during single-incision laparoscopic cholecystectomy (SILC). METHODS: Our SILC procedure utilized the SILS-Port with additional 5-mm forceps through an umbilical incision. A laparoscopic fluorescent imaging system developed by Karl Storz Endoskope was utilized for fluorescent cholangiography. RESULTS: We performed fluorescent cholangiography during SILC in 21 patients. All procedures were completed successfully without biliary injury. The detectability of the running course of the cystic duct, the confluence between the cystic duct and the common hepatic duct, and the common hepatic duct before the dissection in Calot's triangle was 47.6, 71.4, and 81.0 %, respectively. The detectability of biliary structures was worse in 9 obese patients (body mass index >= 25.0 kg/m2) than in 12 non-obese patients. The mean operative time for the patients in whom fluorescent cholangiography could identify the running course of the cystic duct before dissection in Calot's triangle (68 +/- 16 min) was shorter than that for the other patients (91 +/- 35 min; p = 0.037). CONCLUSIONS: Fluorescent cholangiography can prevent biliary injury during SILC and facilitate SILC. Obesity is the most important factor that can prevent identification of biliary structures under fluorescent cholangiography. PMID- 27002712 TI - Guanosine and its role in neuropathologies. AB - Guanosine is a purine nucleoside thought to have neuroprotective properties. It is released in the brain under physiological conditions and even more during pathological events, reducing neuroinflammation, oxidative stress, and excitotoxicity, as well as exerting trophic effects in neuronal and glial cells. In agreement, guanosine was shown to be protective in several in vitro and/or in vivo experimental models of central nervous system (CNS) diseases including ischemic stroke, Alzheimer's disease, Parkinson's disease, spinal cord injury, nociception, and depression. The mechanisms underlying the neurobiological properties of guanosine seem to involve the activation of several intracellular signaling pathways and a close interaction with the adenosinergic system, with a consequent stimulation of neuroprotective and regenerative processes in the CNS. Within this context, the present review will provide an overview of the current literature on the effects of guanosine in the CNS. The elucidation of the complex signaling events underlying the biochemical and cellular effects of this nucleoside may further establish guanosine as a potential therapeutic target for the treatment of several neuropathologies. PMID- 27002715 TI - The effect of foot position on Power Doppler Ultrasound grading of Achilles enthesitis. AB - The aim of this study was to determine whether foot position could modify power Doppler grading in evaluation of the Achilles enthesis. Eighteen patients with clinical Achilles enthesitis were studied with power Doppler ultrasound (PDUS) in five different positions of the foot: active and passive dorsiflexion, neutral position, active and passive plantar flexion. The Doppler signal was graded in any position and compared with the others. The Doppler signal was higher with the foot in plantar flexion and decreased gradually, sometimes till to disappear, while increasing dorsiflexion. The Doppler signal was always less during the active keeping of the position of the joint, than during the passive. The PDUS examination of the Achilles enthesis should be performed also with the foot in passive plantar flexion, in order not to underestimate the degree of vascularization. PMID- 27002716 TI - The Cavitron ultrasonic surgical aspirator with a low amplitude is a useful dissection device for surgical procedures: application to vascular detachment and lymph node dissection. AB - In surgical procedures, although resection and hemostasis maneuvers have become more efficient through the use of dedicated devices, no dedicated device for the dissecting (detaching) maneuver exists at present. The Cavitron ultrasonic surgical aspirator (CUSA: Integra lifesciences Corporation, NJ, USA) is a device originally used mainly for hepatic parenchyma resection in the gastrointestinal surgical field. Tissue is selectively fragmented by an ultrasonically vibrating chip at the tip of the device. Furthermore, physiologic saline is ejected from the tip and aspirated with the fragmented tissue by the device. By reducing the amplitude of the CUSA to 10-20 %, we have been using the device not only for hepatic parenchyma resection but also for dissection in gastrointestinal surgical procedures in general. Here, we explain the details of the techniques that we routinely use, such as dissection of vessels and lymph nodes in radical operations for gastrointestinal cancer. With the CUSA set at a greatly reduced amplitude, dissection can be performed in consideration of layers, surfaces, and membranes while tissue damage and bleeding are minimized. The device is useful for performing higher quality operations. PMID- 27002718 TI - Matrix effects on a cell-based assay used for the detection of paralytic shellfish toxins in bivalve shellfish samples. AB - Detecting marine biotoxins such as paralytic shellfish toxins (PSTs) is essential to ensuring the safety of seafood. The mouse bioassay is the internationally accepted method for monitoring PSTs, but technical and ethical issues have led to a search for new detection methods. The mouse neuroblastoma cell-based assay (Neuro-2a CBA) using ouabain and veratridine (O/V) has proven useful for the detection of PSTs. However, CBAs are sensitive to shellfish-associated matrix interferences. As the extraction method highly influences matrix interferences, this study compared three extraction protocols: Association of Official Analytical Chemists (AOAC) 2005.06, AOAC 2011.02 and an alternative liquid-liquid method. These methods were used to assess the matrix effect of extracts from four commercially important bivalve species (Chilean mussel, Magellan mussel, clam and Pacific oyster) in Neuro-2a CBA. Extracts from all three protocols caused a toxic effect in Neuro-2a cells (without O/V) when tested at a concentration of 25 mg of tissue-equivalent (TE) ml(-1). The greatest toxicity was obtained through the AOAC 2011.02 protocol, especially for the Chilean mussel and Pacific oyster extracts. Similar toxicity levels (less than 15%) were observed in all extracts at 3.1 mg TE ml(-1). When assessed in Neuro-2a CBA, AOAC 2005.06 extracts presented the lowest matrix interferences, while the highest interferences were observed for AOAC 2011.02 in Magellan mussel and clam extracts. Finally, the AOAC 2005.06 and alternative protocols were compared using Chilean mussel samples fortified with 40 and 80 ug STX per 100 g meat. The AOAC 2005.06 method demonstrated better results. In conclusion, the AOAC 2005.06 extracts exhibited the fewest interferences in the Neuro-2a CBA. Therefore, this extraction method should be considered for the implementation of Neuro-2a CBA as a high-throughput screening methodology for PST detection. PMID- 27002717 TI - Hypertension, Blood Pressure Variability, and Target Organ Lesion. AB - Hypertensive patients have a higher risk of developing health complications, particularly cardiovascular (CV) events, than individuals with normal blood pressure (BP). Severity of complications depends on the magnitude of BP elevation and other CV risk factors associated with the target organ damage. Therefore, BP control and management of organ damage may contribute to reduce this risk. BP variability (BPV) has been considered a physiological marker of autonomic nervous system control and may be implicated in increased CV risk in hypertension. This review will present some evidence relating BPV and target organ damage in hypertension in clinical and experimental settings. PMID- 27002719 TI - alpha-Mangostin Inhibits alpha-Synuclein-Induced Microglial Neuroinflammation and Neurotoxicity. AB - Microglia-mediated neuroinflammation induced by alpha-synuclein in the substantianigra likely either initiates or aggravates nigral neuro degeneration in Parkinson's disease (PD). We aimed to explore the effects of alpha-mangostin (alpha-M), a polyphenolicxanthone derivative from mangosteen on alpha-synuclein stimulated DA neurodegeneration. Primary microglia, mesencephalic neuron, mesencephalic neuron-glianeuronal cultures, and transwell co-cultures were prepared separately. Liquid scintillation counting was used to determine the radioactivity in DA uptake. Enzyme-linked immunosorbent assay (ELISA) was performed in the IL-1beta, IL-6, and TNF-alpha assay. The expression of proteins was analyzed by Western blot. alpha-M inhibited the increased levels of pro inflammatory cytokines, NO, and ROS in alpha-synuclein-stimulated primary microglia. Mechanistic study revealed that alpha-M functioned by inhibition of nuclear factor kappa B (NF-kappaB) and NADPH oxidase. Further, alpha-M protected alpha-synuclein-induced microglial and direct neurotoxicity. Although detailed mechanisms remain to be defined, our observations suggest a potential compound, which inhibits microglial activation induced by alpha-synuclein by targeting NADPH oxidase, might be a therapeutic possibility in preventing PD progression. PMID- 27002720 TI - Involvement of Fra-1 in Retinal Ganglion Cell Apoptosis in Rat Light-Induced Retina Damage Model. AB - Cell cycle re-entry, in which Fra-1 (transcription factor FOS-related antigen 1) plays an important role, is a key process in neuronal apoptosis. However, the expression and function of Fra-1 in retinal ganglion cell (RGC) apoptosis are unknown. To investigate whether Fra-1 was involved in RGC apoptosis, we performed a light-induced retinal damage model in adult rats. Western blot revealed that up regulation of Fra-1 expression appeared in retina after light exposure (LE). Immunostaining indicated that increased Fra-1 was mainly expressed in RGCs in retinal ganglion cell layer (GCL) after LE. Co-localization of Fra-1 with active caspase-3 or TUNEL-positive cells in GCL after LE was also detected. In addition, Fra-1 expression increased in parallel with cyclin D1 and phosphorylated mitogen activated protein kinase p38 (p-p38) expression in retina after LE. Furthermore, Fra-1, cyclin D1, and active caspase-3 protein expression decreased by intravitreal injection of SB203580, a highly selective inhibitor of p38 MAP kinase (p38 MAPK). All these results suggested that Fra-1 may be associated with RGC apoptosis after LE regulated by p38 MAPK through cell cycle re-entry mechanism. PMID- 27002721 TI - Precursor miR-499a Variant but not miR-196a2 is Associated with Rheumatoid Arthritis Susceptibility in an Egyptian Population. AB - INTRODUCTION: Rheumatoid arthritis (RA) has a complex component induced by several genes that interact together with environmental and hormonal factors. We aimed to investigate the association of miR-196a2 rs11614913 (C/T) and miR-499a rs3746444 (A/G) polymorphisms and their combination with RA susceptibility and disease activity in an Egyptian population, and to evaluate their impact on methotrexate drug response and toxicity. MATERIALS AND METHODS: Bioinformatics databases were searched to select potential micro RNA (miRNA)-messenger RNA (mRNA) interactions involved in RA pathogenesis. Ninety-five RA patients diagnosed according to the American College of Rheumatology and 200 healthy controls were genotyped using real-time polymerase chain reaction technology. RESULTS: In overall and stratified analysis, miR-499a, but not miR-196a2, was associated with RA risk. Heterozygote carriers with rs3746444*A/G displayed protection against developing RA (p = 0.005) with an odds ratio of 0.2 (95 % confidence interval 0.17-0.62). The carriage of the combinations (miR499a*AG + miR196a2*CC) and (miR499a*AA + miR196a2*TT) were 3 and 7.5 times more likely to develop RA, respectively, while the combinations (miR499a*GG + miR196a2*CC), (miR499a*AG + miR196a2*TT) and (miR499a*AA + miR196a2*CT) show less susceptibility to have RA disease (all p < 0.05). rs3746444*AA genotype had a higher disease activity score (DAS28) [p = 0.023], tender joint count (TJC) (p = 0.007), and methotrexate-induced gastrointestinal toxicity (p = 0.043) compared with both AG/GG genotypes. rs11614913*C carriers were associated with higher DAS28 activity (p = 0.021). Homozygote male patients (CC and TT) had higher TJC (p = 0.046) and higher rheumatoid factor levels (p = 0.026), whereas, TT homozygote females had higher levels of ALT (p = 0.022). CONCLUSIONS: Different genotypes of miR-499a rs3746444 single nucleotide polymorphisms (SNPs) are associated with RA risk, disease activity, and methotrexate toxicity in our population. In combination with specific miR-196a2 rs11614913 genotypes, this risk could increase or decrease according to the type of combination. Further functional analysis of the SNP and its impact on mRNA targets is required to confirm the relationship between genotype and phenotype. PMID- 27002722 TI - A Comparative Study on the In Vitro Effects of the DNA Methyltransferase Inhibitor 5-Azacytidine (5-AzaC) in Breast/Mammary Cancer of Different Mammalian Species. AB - Murine models are indispensible for the study of human breast cancer, but they have limitations: tumors arising spontaneously in humans must be induced in mice, and long-term follow up is limited by the short life span of rodents. In contrast, dogs and cats develop mammary tumors spontaneously and are relatively long-lived. This study examines the effects of the DNA methyltransferase (DNMT) inhibitor 5-Azacytidine (5-AzaC) on normal and tumoral mammary cell lines derived from dogs, cats and humans, as proof of concept that small companion animals are useful models of human breast cancer. Our findings show that treatment with 5 AzaC reduces in vitro tumorigenicity in all three species based on growth and invasion assays, mitochondrial activity and susceptibility to apoptosis. Interestingly, we found that the effects of 5-AzaC on gene expression varied not only between the different species but also between different tumoral cell lines within the same species, and confirmed the correlation between loss of methylation in a specific gene promotor region and increased expression of the associated gene using bisulfite sequencing. In addition, treatment with a high dose of 5-AzaC was toxic to tumoral, but not healthy, mammary cell lines from all species, indicating this drug has therapeutic potential. Importantly, we confirmed these results in primary malignant cells isolated from canine and feline adenocarcinomas. The similarities observed between the three species suggest dogs and cats can be useful models for the study of human breast cancer and the pre-clinical evaluation of novel therapeutics. PMID- 27002723 TI - A microwave antigen retrieval method using two heating steps for enhanced immunostaining on aldehyde-fixed paraffin-embedded tissue sections. AB - Antigen retrieval is an immunohistochemical procedure that results in better exposure of target antigens in aldehyde-fixed, paraffin-embedded tissue sections to antibodies. However, the commercially recommended or conventional protocols for antigen retrieval do not always succeed in expressing the target antigen. Here, an improved method was developed for antigen retrieval from aldehyde-fixed, paraffin-embedded histological sections. Proliferating cell nuclear antigen (PCNA), tight junction proteins Claudin-2 and Claudin-7, and water channel aquaporins in kidney tissue were selected as test antigens. Typically, PCNA and Claudin-2 and Claudin-7 show negative, weak, or nonspecific immunoreactions with conventional antigen retrieval methods using microwave heating. In the present study, microwave heating was performed twice with an interval of 30 min between the two steps to allow the buffer solution to cool. Sodium citrate buffer (10 mM sodium citrate, pH 6.0) was used for PCNA, and Tris-EDTA buffer (10 mM Tris, 1 mM EDTA, pH 9.0) was used for the Claudins. Compared with conventionally prepared tissues, the tissues exhibited both enhanced and specific immunostaining, and well-preserved morphology. In conclusion, the conventional protocol could be supplemented with a second microwave heating step to improve the expression of antigens that do not respond well to the conventional method. PMID- 27002724 TI - Super-Resolution Imaging of Molecular Emission Spectra and Single Molecule Spectral Fluctuations. AB - Localization microscopy can image nanoscale cellular details. To address biological questions, the ability to distinguish multiple molecular species simultaneously is invaluable. Here, we present a new version of fluorescence photoactivation localization microscopy (FPALM) which detects the emission spectrum of each localized molecule, and can quantify changes in emission spectrum of individual molecules over time. This information can allow for a dramatic increase in the number of different species simultaneously imaged in a sample, and can create super-resolution maps showing how single molecule emission spectra vary with position and time in a sample. PMID- 27002725 TI - Increased Intraocular Pressure and Hyperglycemic Level in Diabetic Patients. AB - PURPOSE: To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: A retrospective chart review was performed on subjects with a diagnosis of NPDR and a corresponding HbA1c level measured within 90 days before or after an IOP measurement over a two-year period. Exclusion criteria included a diagnosis of glaucoma or treatment with IOP lowering medications or oral or topical steroids. RESULTS: Using 14.5mmHg as a baseline mean value for IOP, 42 subjects had an IOP < 14.5mmHg and mean HbA1c of 8.1+/-1.1, while 72 subjects had an IOP >= 14.5mmHg and a mean HbA1c of 9.0+/-2.1. Although there was an overlap in the confidence intervals, a significant difference (P = 0.01) in the mean HbA1c level was observed in regression analysis between the two groups. Importantly, diabetic subjects with elevated HbA1c levels rarely (<1%) exhibited reduced IOP levels. CONCLUSIONS: Diabetic subjects with elevated HbA1c levels exhibited significantly higher IOPs compared to those with lower HbA1c levels. Findings from this study indicate an association between hyperglycemia and elevated IOP and that poor glycemic control may contribute to increased IOP levels in long-term diabetic patients. PMID- 27002726 TI - Computer-Assisted Orthognathic Surgery for Patients with Cleft Lip/Palate: From Traditional Planning to Three-Dimensional Surgical Simulation. AB - BACKGROUND: Although conventional two-dimensional (2D) methods for orthognathic surgery planning are still popular, the use of three-dimensional (3D) simulation is steadily increasing. In facial asymmetry cases such as in cleft lip/palate patients, the additional information can dramatically improve planning accuracy and outcome. The purpose of this study is to investigate which parameters are changed most frequently in transferring a traditional 2D plan to 3D simulation, and what planning parameters can be better adjusted by this method. PATIENTS AND METHODS: This prospective study enrolled 30 consecutive patients with cleft lip and/or cleft palate (mean age 18.6+/-2.9 years, range 15 to 32 years). All patients received two-jaw single-splint orthognathic surgery. 2D orthodontic surgery plans were transferred into a 3D setting. Severe bony collisions in the ramus area after 2D plan transfer were noted. The position of the maxillo mandibular complex was evaluated and eventually adjusted. Position changes of roll, midline, pitch, yaw, genioplasty and their frequency within the patient group were recorded as an alternation of the initial 2D plan. Patients were divided in groups of no change from the original 2D plan and changes in one, two, three and four of the aforementioned parameters as well as subgroups of unilateral, bilateral cleft lip/palate and isolated cleft palate cases. Postoperative OQLQ scores were obtained for 20 patients who finished orthodontic treatment. RESULTS: 83.3% of 2D plans were modified, mostly concerning yaw (63.3%) and midline (36.7%) adjustments. Yaw adjustments had the highest mean values in total and in all subgroups. Severe bony collisions as a result of 2D planning were seen in 46.7% of patients. Possible asymmetry was regularly foreseen and corrected in the 3D simulation. CONCLUSION: Based on our findings, 3D simulation renders important information for accurate planning in complex cleft lip/palate cases involving facial asymmetry that is regularly missed in conventional 2D planning. PMID- 27002727 TI - Brachial artery flow mediated dilation and pulsatility index change as independent predictors for hypertensive disorders in the second trimester of pregnancy. AB - OBJECTIVE: To assess brachial artery flow mediated dilatation (FMD) and pulsatility index change (PIC) as independent parameters for prediction hypertensive disorders (preeclampsia - PE and gestational hypertension - GH) in the second trimester of pregnancy. STUDY DESIGN: We performed a prospective cohort study with 372 singleton pregnant women who underwent routine second trimester morphology scan. FMD and PIC were measured immediately after the ultrasound scan using the following formulas: FMD (%)=[(post occlusion arterial diameter-baseline arterial diameter)/baseline arterial diameter]*100 and PIC (%)=[(pulsatility index pre-pulsatility index post)/pulsatility index pre]. The control and hypertensive disorder groups were compared using the Kruskal-Wallis to continue variables and Chi-square and Fisher exact tests to categorical variables. We assessed the predictive accuracy of FMD and PIC by the area under the receiver operating characteristics (ROC) curve with its respective 95% confidence interval (CI). RESULTS: We did not observe statistical difference between control and hypertensive disorder groups regarding the FMD and PIC (p=0.17 and p=0.38, respectively). Areas under ROC curve for prediction of GH using FMD and PIC were 0.59 (CI95% 0.48-0.71) and 0.60 (CI95% 0.47-0.73), respectively. Areas under ROC curve for prediction of PE using FMD and PIC were 0.55 (CI95% 0.46-0.64) and 0.52 (CI95% 0.61-0.69), respectively. CONCLUSION: Brachial artery FMD and PIC as independent parameters did not show good prediction for hypertensive disorders in the second trimester of pregnancy. PMID- 27002728 TI - Diabetes-Related Distress, Depression and Distress-Depression among Adults with Type 2 Diabetes Mellitus in Malaysia. AB - Type 2 diabetes mellitus (T2DM) brings about an increasing psychosocial problem in adult patients. Prevalence data on and associated factors of diabetes related distress (DRD) and depression have been lacking in Asia. This study aimed to examine the prevalence of DRD and depression, and their associated factors in Asian adult T2DM patients. This study was conducted in three public health clinics measuring DRD (Diabetes Distress Scale, DDS), and depression (Patient Health Questionnaire, PHQ). Patients who were at least 30 years of age, had T2DM for more than one year, with regular follow-up and recent laboratory results (< 3 months) were consecutively recruited. Associations between DRD, depression and the combination DRD-depression with demographic and clinical characteristics were analysed using generalized linear models. From 752 invited people, 700 participated (mean age 56.9 years, 52.8% female, 52.9% Malay, 79.1% married). Prevalence of DRD and depression were 49.2% and 41.7%, respectively. Distress and depression were correlated, spearman's r = 0.50. Patients with higher DRD were younger (OR 0.995, 95% CI 0.996 to 0.991), Chinese (OR 1.2, 95% CI 1.04 to 1.29), attending Dengkil health clinic (OR 1.1, 95% CI 1.00 to 1.22) and had higher scores on the PHQ (OR 1.1, 95% CI 1.04 to 1.06). Depression was less likely in the unmarried compared to divorced/separately living and those attending Dengkil health clinic, but more likely in patients with microvascular complications (OR 1.4, 95% CI 1.06 to 1.73) and higher DDS (OR 1.03, 95% CI 1.02 to 1.03). For the combination of DRD and depression, unemployment (OR 4.7, 95% CI 1.02 to 21.20) had positive association, whereas those under medical care at the Salak health clinics (OR 0.28, 95% CI 0.12 to 0.63), and those with a blood pressure > 130/80 mmHg (OR 0.53, 95% CI 0.32 to 0.89) were less likely to experience both DRD and depression. DRD and depression were common and correlated in Asian adults with T2DM at primary care level. Socio-demographic more than clinical characteristics were related to DRD and depression. PMID- 27002729 TI - The Formation of Social Conventions in Real-Time Environments. AB - Why are some behaviors governed by strong social conventions while others are not? We experimentally investigate two factors contributing to the formation of conventions in a game of impure coordination: the continuity of interaction within each round of play (simultaneous vs. real-time) and the stakes of the interaction (high vs. low differences between payoffs). To maximize efficiency and fairness in this game, players must coordinate on one of two equally advantageous equilibria. In agreement with other studies manipulating continuity of interaction, we find that players who were allowed to interact continuously within rounds achieved outcomes with greater efficiency and fairness than players who were forced to make simultaneous decisions. However, the stability of equilibria in the real-time condition varied systematically and dramatically with stakes: players converged on more stable patterns of behavior when stakes are high. To account for this result, we present a novel analysis of the dynamics of continuous interaction and signaling within rounds. We discuss this previously unconsidered interaction between within-trial and across-trial dynamics as a form of social canalization. When stakes are low in a real-time environment, players can satisfactorily coordinate 'on the fly', but when stakes are high there is increased pressure to establish and adhere to shared expectations that persist across rounds. PMID- 27002731 TI - Developmental Age Differentially Mediates the Calcium-Binding Protein Parvalbumin in the Rat: Evidence for a Selective Decrease in Hippocampal Parvalbumin Cell Counts. AB - Local circuit GABAergic neurons, including parvalbumin (PV)-containing basket cells, likely play a key role in the development, physiology, and pathology of neocortical circuits. Regionally selective and well-defined decreases in PV have been described in human postmortem schizophrenic brain tissue in both the hippocampus and prefrontal cortex. Animal models of schizophreniform dysfunction following acute and/or chronic ketamine treatment have also demonstrated decreases in PV expression. Conflicting reports with respect to PV immunoreactivity following acute and chronic ketamine treatments in rodents question the utility of using PV as a biological marker of pathology-related dysfunction. The current literature lacks sufficient and systematic characterization of normative PV expression in pharmacologically and behaviorally naive rodent tissue. In order to understand developmental changes in PV and its putative role in neuropathology, we examined the baseline distribution of the number of cells expressing this protein at distinct developmental ages. The present study examined PV cell counts across the septotemporal axis of the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, as well as within the retrosplenial, somatosensory, and prefrontal cortices, in 1-, 6-, and 12-month old naive rats. Our findings suggest that the hippocampal PV+ cell number significantly decreases as a function of age with considerable regional (CA1, CA3, and DG) and septotemporal variation, a finding that was specific to the hippocampus. Additionally, we observed a modest increase in PV cell number within the prefrontal (anterior cingulate) cortex, which is in line with findings indicating a delayed developmental maturation of this region. The present work highlights decreases in PV+ cell counts within the hippocampus across development, and points to the need for a greater understanding of the role of PV and local circuit developmental changes, as well as consideration of their development when modeling developmentally related neuropathological disorders (e.g. schizophrenia, autism). PMID- 27002732 TI - Correction: Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter, Double Blind, Randomized Controlled Trial. PMID- 27002730 TI - RGS6 as a Novel Therapeutic Target in CNS Diseases and Cancer. AB - Regulator of G protein signaling (RGS) proteins are gatekeepers regulating the cellular responses induced by G protein-coupled receptor (GPCR)-mediated activation of heterotrimeric G proteins. Specifically, RGS proteins determine the magnitude and duration of GPCR signaling by acting as a GTPase-activating protein for Galpha subunits, an activity facilitated by their semiconserved RGS domain. The R7 subfamily of RGS proteins is distinguished by two unique domains, DEP/DHEX and GGL, which mediate membrane targeting and stability of these proteins. RGS6, a member of the R7 subfamily, has been shown to specifically modulate Galphai/o protein activity which is critically important in the central nervous system (CNS) for neuronal responses to a wide array of neurotransmitters. As such, RGS6 has been implicated in several CNS pathologies associated with altered neurotransmission, including the following: alcoholism, anxiety/depression, and Parkinson's disease. In addition, unlike other members of the R7 subfamily, RGS6 has been shown to regulate G protein-independent signaling mechanisms which appear to promote both apoptotic and growth-suppressive pathways that are important in its tumor suppressor function in breast and possibly other tissues. Further highlighting the importance of RGS6 as a target in cancer, RGS6 mediates the chemotherapeutic actions of doxorubicin and blocks reticular activating system (Ras)-induced cellular transformation by promoting degradation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) to prevent its silencing of pro apoptotic and tumor suppressor genes. Together, these findings demonstrate the critical role of RGS6 in regulating both G protein-dependent CNS pathology and G protein-independent cancer pathology implicating RGS6 as a novel therapeutic target. PMID- 27002733 TI - Informing the Historical Record of Experimental Nonhuman Primate Infections with Ebola Virus: Genomic Characterization of USAMRIID Ebola Virus/H.sapiens tc/COD/1995/Kikwit-9510621 Challenge Stock "R4368" and Its Replacement "R4415". AB - The creation of licensed medical countermeasures against Select Agents such as Ebola virus (EBOV) is critically dependent on the use of standardized reagents, assays, and animal models. We performed full genome reconstruction, population genomics, contaminant analysis, and characterization of the glycoprotein gene editing site of historical United States Army Medical Research Institute of Infectious Diseases (USAMRIID) nonhuman-primate challenge stock Ebola virus Kikwit "R4368" and its 2014 replacement "R4415." We also provide characterization of the master stock used to create "R4415." The obtained data are essential to understanding the quality of the seed stock reagents used in pivotal animal studies that have been used to inform medical countermeasure development. Furthermore, these data might add to the understanding of the influence of EBOV variant populations on pathogenesis and disease outcome and inform attempts to avoid the evolution of EBOV escape mutants in response to current therapeutics. Finally, as the primary challenge stocks have changed over time, these data will provide a baseline for understanding and correlating past and future animal study results. PMID- 27002734 TI - Diglycolic acid, the toxic metabolite of diethylene glycol, chelates calcium and produces renal mitochondrial dysfunction in vitro. AB - CONTEXT: Diethylene glycol (DEG) has caused many cases of acute kidney injury and deaths worldwide. Diglycolic acid (DGA) is the metabolite responsible for the renal toxicity, but its toxic mechanism remains unclear. OBJECTIVE: To characterize the mitochondrial dysfunction produced from DGA by examining several mitochondrial processes potentially contributing to renal cell toxicity. MATERIALS AND METHODS: The effect of DGA on mitochondrial membrane potential was examined in normal human proximal tubule (HPT) cells. Isolated rat kidney mitochondria were used to assess the effects of DGA on mitochondrial function, including respiratory parameters (States 3 and 4), electron transport chain complex activities and calcium-induced opening of the mitochondrial permeability transition pore. DGA was compared with ethylene glycol tetraacetic acid (EGTA) to determine calcium chelating ability. DGA cytotoxicity was assessed using lactate dehydrogenase leakage from cultured proximal tubule cells. RESULTS: DGA decreased the mitochondrial membrane potential in HPT cells. In rat kidney mitochondria, DGA decreased State 3 respiration, but did not affect State 4 respiration or the ADP/O ratio. DGA reduced glutamate/malate respiration at lower DGA concentrations (0.5 mmol/L) than succinate respiration (100 mmol/L). DGA inhibited Complex II activity without altering Complex I, III or IV activities. DGA blocked calcium induced mitochondrial swelling, indicating inhibition of the calcium-dependent mitochondrial permeability transition. DGA and EGTA reduced the free calcium concentration in solution in an equimolar manner. DGA toxicity and mitochondrial dysfunction occurred as similar concentrations. DISCUSSION: DGA inhibited mitochondrial respiration, but without uncoupling oxidative phosphorylation. The more potent effect of DGA on glutamate/malate respiration and the inhibition of mitochondrial swelling was likely due to its chelation of calcium. CONCLUSION: These results indicate that DGA produces mitochondrial dysfunction by chelating calcium to decrease the availability of substrates and of reducing equivalents to access Complex I and by inhibiting Complex II activity at higher concentrations. PMID- 27002735 TI - New variant of an imipenemase, IMP-32, in Klebsiella pneumoniae from a fatal case of a Thai patient. PMID- 27002736 TI - Effects of functional endoscopic sinus surgery on the treatment of bronchiectasis combined with chronic rhino-sinusitis. AB - CONCLUSION: Idiopathic bronchiectasis is closely associated with chronic rhino sinusitis. It can effectively control bronchiectasic symptoms to treat chronic rhino-sinusitis by FESS in the cases with bronchiectasis and chronic rhino sinusitis. OBJECTIVE: To explore the effect of functional endoscopic sinus surgery (FESS) on the treatment of bronchiectasis combined with chronic rhino sinusitis. METHODS: In this study, a total of 161 cases with bronchiectasis and chronic rhino-sinusitis were divided into medication group and operation group according to the therapeutic method for chronic rhino-sinusitis selected by them. For the treatment of chronic rhino-sinusitis, the cases in the operation group received FESS, but in the medication group cases took drugs alone. The score of clinical symptoms for bronchiectasis, forced expiratory volume in one second (FEV1), SNOT-22 score, and Lund-Mackay score were evaluated for all cases before and after treatment, respectively, and then the value changes in the score of clinical symptoms, FEV1, SNOT-22 score, and Lund-Mackay score between both time points were calculated. The frequency of acute exacerbation for bronchiectasis was also recorded within the 6-month follow-up. RESULTS: In this study, 58.9% of cases with bronchiectasis had chronic rhino-sinusitis. Follow-up lasted 6 months. Compared with pre-therapy, post-therapy score of clinical symptoms, SNOT-22 score, and Lund-Mackay score were all significantly decreased (all p < 0.05), but post-therapy FEV1 failed to significantly improve (p > 0.05) in both groups. During the 6-month follow-up, the frequency of acute exacerbation was significantly less in the operation group than in the medication group (p < 0.01). Post-treatment score of clinical symptoms (p < 0.01), SNOT-22 score (p < 0.05), and Lund-Mackay score (p < 0.05) also were all significantly less in the operation group than in the medication group. However, there was no significant difference in post-therapy FEV1 between the two groups (p > 0.05). PMID- 27002739 TI - Cranial bone regeneration via BMP-2 encoding mesenchymal stem cells. AB - Cranial bone repair and regeneration via tissue engineering principles has attracted a great deal of interest from researchers during last decade. Here, within this study, 6 mm critical-sized bone defect regeneration via genetically modified mesenchymal stem cells (MSC) were monitored up to 4 months. Cranial bone repair and new bone formations were evaluated by histological staining and real time PCR analysis in five different groups including autograft and bone morphogenetic protein-2 (BMP-2) transfected MSC groups. Results presented here indicate a proper cranial regeneration in autograft groups and a prospering regeneration for hBMP-2 encoding mesenchymal stem cells. PMID- 27002738 TI - Genetic link between renal birth defects and congenital heart disease. AB - Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD. PMID- 27002740 TI - Toward a Tailored Treatment of Achalasia: An Evidence-Based Approach. AB - BACKGROUND: The treatment options in achalasia patients aim to improve symptoms by reducing the functional obstruction at the level of the gastroesophageal junction. Available treatment modalities are endoscopic botulinum toxin injection (EBTI), pneumatic dilatation (PD), laparoscopic Heller myotomy (LHM), and peroral endoscopic myotomy (POEM). We provide an evidence-based review of current indications, limitations, and future perspectives of these options for the treatment of achalasia. METHODS: The PubMed/Medline electronic databases and the Cochrane Library were searched. Quality of evidence was assessed according to the GRADE system. RESULTS: Functional outcomes after EBTI are significantly worse than those after PD or LHM. LHM with partial fundoplication is associated with low complication rates and provides excellent long-term results with lower need for additional treatment of recurrent dysphagia than PD. POEM is a new promising treatment option with good short-term outcomes and low morbidity in experienced hands. CONCLUSIONS: LHM should be considered the procedure of choice for the treatment of achalasia in patients who are fit for surgery. Large randomized controlled trials with long follow-up are needed to validate the role of POEM. PMID- 27002737 TI - The unfolded protein response in skeletal development and homeostasis. AB - Osteoblasts and chondrocytes produce a large number of extracellular matrix proteins to generate and maintain the skeletal system. To cope with their functions as secretory cells, these cells must acquire a considerable capacity for protein synthesis and also the machinery for the quality-control and transport of newly synthesized secreted proteins. The unfolded protein response (UPR) plays a crucial role during the differentiation of these cells to achieve this goal. Unexpectedly, however, studies in the past several years have revealed that the UPR has more extensive functions in skeletal development than was initially assumed, and the UPR critically orchestrates many facets of skeletal development and homeostasis. This review focuses on recent findings on the functions of the UPR in the differentiation of osteoblasts, chondrocytes, and osteoclasts. These findings may have a substantial impact on our understanding of bone metabolism and also on establishing treatments for congenital and acquired skeletal disorders. PMID- 27002742 TI - Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy. AB - PURPOSE: The perioperative management of patients on antithrombotic therapy is currently an unresolved problem as these therapies pose a considerable risk for perioperative hemorrhagic complications. The presented studies investigated the efficacy of a new collagen technology to achieve hemostasis. A polyethylene glycol-coated collagen pad (PCC) was compared to a marketed fibrinogen-thrombin coated collagen pad (FTC) for the treatment of an aortotomy incision in heparinized swine on dual antiplatelet therapy. MATERIALS AND METHODS: Twenty eight 3-mm aortotomy incisions were created in nine heparinized pigs without antiplatelet therapy and treated with PCC. Sixty-eight aortotomy incisions were created in ten heparinized pigs that received clopidogrel (10-11 mg/kg) and acetylsalicylic acid (8-11 mg/kg) orally for 5 days, and treated with either PCC or FTC (N = 34/group). Dual antiplatelet therapy resulted in significantly reduced platelet function. Aortotomy incisions resulted in life-threatening bleeding of 35-292 ml/min. RESULTS: In animals without antiplatelet treatment, PCC provided 96% immediate hemostatic success. In animals with antiplatelet treatment, FTC provided 18% immediate hemostatic success increasing to 74% after 10 min. Strikingly, PCC provided 94% immediate success increasing to 100% after 10 min. Controlling for differences in pretreatment bleeding rates, statistical model-estimated time to hemostasis was 12 times shorter in PCC-treated lesions (p < .02). CONCLUSION: The combination of a procoagulant collagen pad with a synthetic sealing component provides excellent hemostatic properties under a worst-case scenario. PCC rapidly and firmly adheres to tissue, thereby controlling severe arterial bleeding, even when platelet function is significantly reduced. Treatment with PCC provided superior time to hemostasis compared to FTC. PMID- 27002743 TI - Gender-related differences in urothelial carcinoma of the bladder: a population based study from the Swedish National Registry of Urinary Bladder Cancer. AB - OBJECTIVE: The aim of this investigation was to describe tumour characteristics, treatments and survival in patients with urinary bladder cancer (UBC) in a national population-based cohort, with special reference to gender-related differences. MATERIAL AND METHODS: All primary UBC patients with urothelial pathology reported to the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) from 1997 to 2011 were included in the study. Groups were compared regarding tumour, node, metastasis classification, primary treatment and survival. RESULTS: In total, 30,310 patients (74.9% male, 25.1% female) with UBC were analysed. A larger proportion of women than men had stage T2-T4 (p < 0.001), and women also had more G1 tumours (p < 0.001). However, compared to women, a larger proportion of men with carcinoma in situ or T1G3 received intravesical treatment with bacillus Calmette-Guerin or intravesical chemotherapy, and a larger proportion of men with stage T2-T4 underwent radical cystectomy (38% men vs 33% women, p < 0.0001). The cancer-specific survival at 5 years was 77% for men and 72% for women (p < 0.001), and the relative survival at 5 years was 72% for men and 69% for women (p < 0.001). CONCLUSIONS: In this population-based cohort comprising virtually all patients diagnosed with UBC in Sweden between 1997 and 2011, female gender was associated with inferior cancer-specific and relative survival. Although women had a higher rate of aggressive tumours, a smaller proportion of women than men received optimal treatment. PMID- 27002744 TI - Migration as a risk and a livelihood strategy: HIV across the life course of migrant families in India. AB - Migrant workers are understood to be vulnerable to HIV. However, little is known about the experience of migration-based households following HIV infection. This qualitative study examined the migration-HIV relationship beyond the point of infection, looking at how it affects livelihood choices, household relationships and the economic viability of migrant families. We conducted semi-structured interviews with 33 HIV-positive migrant men and women recruited from an anti retroviral therapy (ART) centre in north India. Following infection among the migrant men, contact with free, public-sector HIV services was often made late, after the development of debilitating symptoms, abandonment of migrant work and return to native villages. After enrolment at the ART centre participants' health eventually stabilised but they now faced serious economic debt, an inflexible treatment regimen and reduced physical strength. Insecure migrant job markets, monthly drug collection and discriminatory employment policies impeded future migration plans. HIV-positive wives of migrants occupied an insecure position in the rural marital household that depended on their husbands' health and presence of children. The migration-HIV relationship continued to shape the life course of migrant families beyond the point of infection, often exposing them again to the economic insecurity that migration had helped to overcome, threatening their long term survival. PMID- 27002747 TI - Integrated dual-mode 3 dB power coupler based on tapered directional coupler. AB - A dual-mode 3 dB power coupler based on silicon-on-insulator platform for mode division multiplexing system is proposed and demonstrated. The device, which consists of a tapered directional coupler and two output bend waveguides, has a 50:50 coupling ratio around the wavelength of 1550 nm for both fundamental and first order transverse magnetic (TM0 and TM1) modes. Based on asymmetrical tapered structure, a short common coupling length of ~15.2 MUm for both modes is realized by optimizing the width of the tapered waveguide. The measured insertion loss for both modes is less than 0.7 dB. The crosstalks are about -14.3 dB for TM0 mode and -18.1 dB for TM1 mode. PMID- 27002746 TI - Of Disasters and Dragon Kings: A Statistical Analysis of Nuclear Power Incidents and Accidents. AB - We perform a statistical study of risk in nuclear energy systems. This study provides and analyzes a data set that is twice the size of the previous best data set on nuclear incidents and accidents, comparing three measures of severity: the industry standard International Nuclear Event Scale, the Nuclear Accident Magnitude Scale of radiation release, and cost in U.S. dollars. The rate of nuclear accidents with cost above 20 MM 2013 USD, per reactor per year, has decreased from the 1970s until the present time. Along the way, the rate dropped significantly after Chernobyl (April 1986) and is expected to be roughly stable around a level of 0.003, suggesting an average of just over one event per year across the current global fleet. The distribution of costs appears to have changed following the Three Mile Island major accident (March 1979). The median cost became approximately 3.5 times smaller, but an extremely heavy tail emerged, being well described by a Pareto distribution with parameter alpha = 0.5-0.6. For instance, the cost of the two largest events, Chernobyl and Fukushima (March 2011), is equal to nearly five times the sum of the 173 other events. We also document a significant runaway disaster regime in both radiation release and cost data, which we associate with the "dragon-king" phenomenon. Since the major accident at Fukushima (March 2011) occurred recently, we are unable to quantify an impact of the industry response to this disaster. Excluding such improvements, in terms of costs, our range of models suggests that there is presently a 50% chance that (i) a Fukushima event (or larger) occurs every 60-150 years, and (ii) that a Three Mile Island event (or larger) occurs every 10-20 years. Further-even assuming that it is no longer possible to suffer an event more costly than Chernobyl or Fukushima-the expected annual cost and its standard error bracket the cost of a new plant. This highlights the importance of improvements not only immediately following Fukushima, but also deeper improvements to effectively exclude the possibility of "dragon-king" disasters. Finally, we find that the International Nuclear Event Scale (INES) is inconsistent in terms of both cost and radiation released. To be consistent with cost data, the Chernobyl and Fukushima disasters would need to have between an INES level of 10 and 11, rather than the maximum of 7. PMID- 27002748 TI - Managing Pain in Women Living With HIV/AIDS: A Randomized Controlled Trial Testing the Effect of a Six-Week Peer-Led Exercise and Education Intervention. AB - This study tested an intervention program based on a chronic pain management model for pain. We conducted a trial of a 6-week, peer-led exercise and education intervention on pain in amaXhosa women living with HIV/AIDS. Participants were monitored over 15 months of routine care before randomization. The control group was provided with educational workbooks, and the experimental group attended the intervention. Pain was reassessed monthly for 4 months. There was no significant reduction in pain during 15 months of routine care and no difference between groups at any of the time points (d = 0.04). Both groups experienced equivalent pain reduction during the intervention compared with the period of routine care with meaningful reductions in pain at months 3 (Cohen's d = 0.41) and 4 (Cohen's d = 0.59). Provision of a workbook and participating in a 6-week peer-led exercise and education intervention are efficacious methods to treat pain in amaXhosa women living with HIV/AIDS. PMID- 27002749 TI - Childhood Antecedents and Maintaining Factors in Maladaptive Daydreaming. AB - This study explored the fantasy activity of 16 individuals who were seeking online peer-support and advice for maladaptive daydreaming (MD). MD is an under researched mental activity described as persistent vivid fantasy activity that replaces human interaction and/or interferes with important areas of functioning. We employed a grounded theory methodology that yielded seven common themes presented as a sequential descriptive narrative about the nature, precursors, and consequences of MD. The presented "storyline" included the following themes: (1) daydreaming as an innate talent for vivid fantasy; (2) daydreaming and social isolation-a two-way street; (3) the role of trauma in the development of MD; (4) the rewards of daydreaming; (5) the insatiable yearning for daydreaming; (6) shame and concealment; (7) unsuccessful treatment attempts. A main conclusion of our study is that there is an urgent need for early identification of MD and its correct diagnoses in adulthood. PMID- 27002753 TI - Anesthesia for Placement of a Paracorporeal Lung Assist Device and Subsequent Heart-Lung Transplantation in a Child with Suprasystemic Pulmonary Hypertension and End-Stage Respiratory Failure. AB - Pediatric patients with end-stage respiratory failure and pulmonary hypertension traditionally have poor outcomes when bridged with extracorporeal membrane oxygenation to lung or heart-lung transplantation. Therefore, several institutions have attempted paracorporeal lung assist devices as a bridge. However, given the small number of patients, little is known about approaches to anesthetic induction in these hemodynamically unstable patients either before placement of a device or anesthetic induction once a device is in situ. In this case report, we describe our anesthetic experience managing a 13-year-old boy for both paracorporeal lung assist device placement and subsequent heart-lung transplantation. PMID- 27002754 TI - Bilateral Dilated Nonreactive Pupils in a Neonate After Surgery. AB - Fixed and dilated pupils are disturbing when encountered during a physical examination in the pediatric intensive care unit, particularly when sedation or neuromuscular blockade confounds the neurologic examination. Rocuronium, a nondepolarizing neuromuscular drug, does not cross the blood-brain barrier and is not considered a causative agent for fixed mydriasis. We report a case of bilateral fixed and dilated pupils in a 1-week-old low-birth-weight neonate, which we contend was secondary to centrally mediated neuromuscular blockade. PMID- 27002755 TI - Serum TK1 is a more reliable marker than CEA and AFP for cancer screening in a study of 56,286 people. AB - BACKGROUND: The World Health Organization (WHO) has estimated that the number of cancer patients will increase by about 70% during the next 25 years world-wide. To deal with this problem, WHO has suggested a focus on prevention of tumor incidence and health screening for early detection of people with tumors. OBJECTIVE: To investigate the use of thymidine kinase 1 (TK1), CEA and AFP in serum to discover people with malignant tumors through health cancer screening. METHODS: Of a cohort in 486,085 people of a routine health screening at the Health Centre, Fujun 180 Hospital, Quanzhou city, China, 56,286 people were investigated according to the presence of cancer during 2009-2014. The concentration of CEA and AFP were determined by an electrochemiluminescence immunoassay from Roche Diagnostics e601GmbH and STK1 by a commercial kit based on an enhanced chemiluminescent dot blot assay. RESULTS: The cancer incident rate increased from 0.048/100,000 to 0.220/100,000. The most common types of tumors were those of the liver, cervix and lung. STK1 correlated to tumor growth rate, was more sensitive than CEA and AFP for discovering people with malignant tumors and more sensitive among people who had diagnosis of malignant tumor. STK1 was also a prognostic biomarker for death at 10-40 months follow-up, while CEA and AFP were not. A combination of these markers increased the sensitivity by about 30%. CONCLUSION: STK1 is a reliable biomarker for discovering people with malignant tumors in cancer screening. PMID- 27002756 TI - Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentration in urine is superior to CA19-9 and Ca 125 in differentiation of pancreatic mass: Preliminary report. AB - BACKGROUND: Currently pancreatic cancer is the fourth leading cause of cancer related death worldwide. Because of its late manifestation and consequent dismal prognosis, there is an urgent need to develop highly sensitive and specific marker. Neutrophil Gelatinase-Associated Lipocalin (NGAL) recently emerged as a protein playing an important role in carcinogenesis of various neoplasms. OBJECTIVE: Our aim was to assess the potential of urine and bile concentration of NGAL in differentiating pancreatic adenocarcinoma from chronic pancreatitis. METHODS: Forty-two patients operated on due to pancreatobiliary lesions were enrolled in this study. All enrolled patients had eGFR within reference range. Levels of CEA, CA 125 and Ca19-9 were assessed using standard laboratory protocols. A sample of urine was collected prior to the surgery. Intraoperatively a 5 ml sample of bile was collected directly from the common bile duct. Bile and urine levels of NGAL were measured using a ELISA kit. After standard pathological examination of specimens obtained during surgery, patients were divided into 2 groups: 21 patients with pancreatic adenocarcinoma and 15 patients with focal chronic pancreatitis. RESULTS: NGAL concentration in bile in patients with PDAC vs CP was 75.72 +/- 16.05 ng/mL vs 62.62 +/- 18.6 ng/mL respectively (p= 0,011). NGAL concentration in urine was 43.26 +/- 21.21 ng/mL vs 17.96 +/- 14.58 ng/mL (p= 0.002) respectively. In order to compare these markers with routinely used ones, ROC curve was built for Ca125 to establish cutoff point and in case of CA19 9 clinically used cutoff (>= 37U/mL) was applied. Sensitivity and specificity for NGALurine with cutoff value of 27 ng/mL was 80.95% and 80% respectively, while these values for NGALbile were 71.43% and 80% respectively. Ca19-9 measured in plasma with clinically used cutoff value had sensitivity of 71.43% and specificity of 73.33%. Sensitivity and specificity for Ca 125 measured in plasma with cutoff value of 13 U/mL were 85.71% and 66.67% respectively. CONCLUSIONS: In conclusion, NGAL in urine and bile are remarkably accurate in differentiating pancreatic mass due to chronic pancreatitis from pancreatic adenocarcinoma. Therefore, NGAL concentrations in bile and urine should be further investigated in order to assess their usefulness in early pancreatic adenocarcinoma diagnosis. PMID- 27002757 TI - Higher circulating levels of chemokine CXCL10 in patients with breast cancer: Evaluation of the influences of tumor stage and chemokine gene polymorphism. AB - BACKGROUND: The CXCL10 receptor, CXCR3, is preferentially expressed on Th1 and NK cells. Therefore, CXCL10 acts as a chemoattractant for these cells. OBJECTIVE: The aim was to evaluate the CXCL10 levels and a single nucleotide polymorphism (SNP), rs4508917, in chemokine gene, in patients with breast cancer (BC). METHODS: A total of 200 subjects including 100 women with BC and 100 healthy women were enrolled into study. The serum CXCL10 levels were measured by ELISA and the SNP rs4508917 was determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). RESULTS: The CXCL10 levels were significantly higher in patients than control group (P< 0.0001). There was also significant difference between tumor stages regarding the CXCL10 levels (P< 0.0001). The frequencies of GG genotype and G allele at rs4508917 were significantly higher in patients than controls (P< 0.0001). The CXCL10 levels were higher in patients with GG genotype whereas they were lower in healthy subjects having GG genotype as compared with those having AA genotype at rs4508917 (P< 0.001). CONCLUSION: Higher CXCL10 levels in patients with BC represent that the chemokine may contributes in tumor development. The rs4508917 may play a role in the susceptibility to BC. Different association was also observed between rs4508917 and CXCL10 levels in patients with BC and healthy subjects. PMID- 27002758 TI - Inflammatory myofibroblastic duodenal tumor: A rare cause of massive intestinal bleeding. AB - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor, which can develop in nearly all anatomical locations. It is extremely rare in the duodenum and only seven cases have been reported previously.These lesions are of unknown etiology characterized by proliferation of myofibroblastic with an inflammatory infiltrate. It is considered a tumor of borderline malignancy. OBJECTIVE: We report the first case described of IMT located isolated in the third duodenal portion, which develops as a massive intestinal bleeding in a 14 years old girl. RESULTS: Complete surgical excision was successful and after 36 months of follow up the patient is asymptomatic. PMID- 27002759 TI - New miRNA expression abnormalities in laryngeal squamous cell carcinoma. AB - BACKGROUND: Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers - and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS: We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21 3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR 885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21 3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa. PMID- 27002760 TI - Anaplastic lymphoma kinase (ALK) gene alteration in gastric signet ring cell carcinoma. AB - BACKGROUND: This study was aimed to investigating the frequency of Anaplastic lymphoma kinase (ALK) alterations in patients with gastric signet ring cell carcinoma (SRC) and the correlations between ALK alterations and the clinical pathological features. METHODS: The expression of ALK protein was first determined in paraffin-embedded tissue specimens (FFPE) from 177 pathologically confirmed SRC patients by Ventana Immunohistochemistry (IHC). Then patients with ALK positive detected by IHC were assayed in ALK rearrangement by Fluorescence in Situ Hybridization (FISH). RESULTS: We assessed 4 of 177 cases (2.3%) as positive by IHC. 3 of the 4 patients had T4 tumors and positive nodal status, and 1 of them had metastasis. All of them were HER2 negative. All of the 4 patients were positive for ALK rearrangement using the standard criteria of FISH. COUCLUSION: Our analysis showed that about 2.3% of Chineses SRC patients treated in our hospital were ALK positive. Ventana IHC and FISH were both of the reliable approaches in SRC patients. Patients with ALK positive seemed to have deep infiltrated and positive lymph nodes and HER2 negative. PMID- 27002761 TI - Copy number variation in archival melanoma biopsies versus benign melanocytic lesions. AB - BACKGROUND: Skin melanocytes can give rise to benign and malignant neoplasms. Discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. However, previous studies have shown that in contrast to benign nevi, melanoma demonstrates pervasive chromosomal aberrations. OBJECTIVE: This substantial difference between melanoma and benign nevi can be exploited to discriminate between melanoma and benign nevi. METHODS: Array comparative genomic hybridization (aCGH) is an approach that can be used on DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues to assess the entire genome for the presence of changes in DNA copy number. In this study, high resolution, genome-wide single-nucleotide polymorphism (SNP) arrays were utilized to perform comprehensive and detailed analyses of recurrent copy number aberrations in 41 melanoma samples in comparison with 21 benign nevi. RESULTS: We found statistically significant copy number gains and losses within melanoma samples. Some of the identified aberrations are previously implicated in melanoma. Moreover, novel regions of copy number alterations were identified, revealing new candidate genes potentially involved in melanoma pathogenesis. CONCLUSIONS: Taken together, these findings can help improve melanoma diagnosis and introduce novel melanoma therapeutic targets. PMID- 27002762 TI - Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients. AB - BACKGROUND: Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. OBJECTIVE: The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. METHODS: Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). RESULTS: Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP 11 level as an independent predictor of OS and DFS. CONCLUSION: Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients. PMID- 27002763 TI - Serum phosphatidylethanolamine levels distinguish benign from malignant solitary pulmonary nodules and represent a potential diagnostic biomarker for lung cancer. AB - BACKGROUND: Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable. OBJECTIVE: Identify blood-based metabolite biomarkers for diagnosing lung cancer. MEHTODS: Serum samples from subjects participating in a CT screening trial were analyzed using untargeted GC-TOFMS and HILIC-qTOFMS-based metabolomics. Samples were acquired prior to diagnosis (pre-diagnostic, n= 17), at-diagnosis (n= 25) and post-diagnosis (n= 19) of lung cancer and from subjects with benign nodules (n= 29). RESULTS: Univariate analysis identified 40, 102 and 30 features which were significantly different between subjects with malignant (pre-, at- and post diagnosis) solitary pulmonary nodules (SPNs) and benign SPNs, respectively. Ten metabolites were consistently different between subjects presenting malignant (pre- and at-diagnosis) or benign SPNs. Three of these 10 metabolites were phosphatidylethanolamines (PE) suggesting alterations in lipid metabolism. Accuracies of 77%, 83% and 78% in the pre-diagnosis group and 69%, 71% and 67% in the at-diagnosis group were determined for PE(34:2), PE(36:2) and PE(38:4), respectively. CONCLUSIONS: This study demonstrates evidence of early metabolic alterations that can possibly distinguish malignant from benign SPNs. Further studies in larger pools of samples are warranted. PMID- 27002764 TI - Beclin-1 and hypoxia-inducible factor-1alpha genes expression: Potential biomarkers in acute leukemia patients. AB - BACKGROUND: Beclin-1, an important autophagic gene, and hypoxia-inducible factor 1alpha (HIF-1alpha), the master regulator of the hypoxic response, are reported in several human cancers. However, their expressions in acute leukemia haven't yet been well investigated. OBJECTIVE: This study was designed to investigate the gene expression of beclin-1, microtubule-associated protein-1 light chain-3B (MAB1LC3B), the anti-apoptotic marker Bcl-2, and HIF-1alpha, as well as to evaluate the relationship between their expressions profile and prognosis in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) adult patients. METHODS: The study involved 30 AML patients, 25 ALL patients, and 20 controls. Gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). RESULTS: In both AML and ALL groups, beclin 1 and MAB1LC3B expressions were significantly down-regulated (p < 0.001), while HIF-1alpha (p < 0.01) and Bcl-2 (p < 0.001) expressions were significantly up regulated compared to the control group. HIF-1alpha fold expression was significantly negatively correlated with beclin-1 (p < 0.01). Moreover, decreased beclin-1 gene expression and increased HIF-1alpha gene expression were both associated with poor survival, supporting their pivotal role in the development and progression of acute leukemia. CONCLUSIONS: Both Beclin-1 and HIF-1alpha could be considered as important biomarkers determinants of pathogenesis and survival in acute leukemia. PMID- 27002765 TI - MGMT hypermethylation and BCL-2 overexpression associated with superficial bladder cancer and recurrence. AB - BACKGROUND: Urinary bladder carcinoma is one of the leading causes of death among men, and its high recurrence rates make it one of the most solid tumors to treat. The silencing of the tumor suppressor gene by hypermethylation of the CpG islands and overexpression of proto-oncogene proteins are the main mechanisms in cancers. Here, we investigate methylation status of O6-methylguanine-DNA-methyltransferase (MGMT), a tumor suppressor gene and expression level of BCL-2 a proto-oncogene protein that is frequently observed in bladder carcinoma and its recurrences. MATERIALS AND METHODS: We analyzed the methylation of MGMT in 80 tissue samples of patients suffering from bladder cancer and 80 urine samples of cancer-free individuals by MS-PCR. Additionally, BCL-2 protein expression level was analyzed on these 80 tissue samples by immunohistochemistry. RESULTS: 45% of patients had MGMT methylation, of which this hypermethylation does not have significant association with an increase in grade, but there was significant association in cases with recurrence tumors and metastasis tumors. Among patients with recurrence tumor, 92.5% patients showed MGMT hypermethylation; 66% of these showed BCL-2 overexpression. CONCLUSION: Our data indicate that MGMT hypermethylation and BCL-2 overexpression may have an intense role in superficial bladder cancer recurrences. PMID- 27002766 TI - PARP1 is a novel independent prognostic factor for the poor prognosis of chordoma. AB - OBJECTIVE: To evaluate the expression of PARP1 in chordoma and analyzed its association with clinical factors and patients' prognosis. METHODS: The expression of Poly (ADP-ribose) polymerase 1 (PARP1) in chordoma specimens from 74 chordoma patients (50 primary and 24 recurrent tumors of 50 patients)and 20 distant normal tissue specimens was measured by immunohistochemical staining. The association of PARP1with the clinical factors and patients' prognosis was also analyzed. RESULTS: Of all the chordoma samples, 78% showed high expression of PARP1, whereas, only 10% of distant normal tissues expressed a high level of PARP1 (p< 0.01). Chi-square analysis revealed that high expression of PARP1 was significantly correlated with tumor recurrence (p< 0.01) and invasion into surrounding muscle (p< 0.01), while the data did not indicate any association with patients' gender, age, tumor location and size (p> 0.05). Kaplan-Meier survival curve and log-rank test showed that continuous disease free survival time (CDFS) was significantly shorter in the PARP1-positive group than in the PARP1-negative group (P= 0.019). CONCLUSION: High expression of PARP1 is significantly associated with chordoma invasion and recurrence. PARP1 may become a potential biomarker for chordoma in predicting its recurrence and patients' prognosis. PMID- 27002767 TI - Functional polymorphisms in the IL-10 gene with susceptibility to esophageal, nasopharyngeal, and oral cancers. AB - Emerging evidence showed that functional polymorphisms in the IL-10 gene may have effects on individuals' susceptibility to nasopharyngeal, oral and esophageal cancers, yet individually published findings are inconsistent. We therefore designed the meta-analysis to investigate the correlations of IL-10 genetic polymorphisms with susceptibility to nasopharyngeal, oral and esophageal cancers. The EMBASE, MEDLINE, CINAHL, Web of Science and the Chinese Biomedical Database (CBM) databases were searched with no language restrictions. We use Comprehensive Meta-analysis 2.0 software to carry out statistical analysis. Ten case-control studies with a number of 1,883 patients and 2,857 healthy subjects were enrolled. Our results revealed that IL-10 rs1800872 T>G and rs1800896 A>G polymorphisms has a significantly association with the increased risk of esophageal cancer under the allele and dominant models; rs1800871 T>G, rs1800872 T>G and rs1800896 A>G under allele and dominant models could increase the risk of nasopharyngeal cancer; rs1800871T>G, rs1800872T>G and rs1800896 A>G SNPs under allele model were closely related to the susceptibility to oral cancer. Our findings support the point that IL-10 genetic polymorphisms may play essential role in identifying esophageal cancer, nasopharyngeal cancer and oral cancer at early stage. PMID- 27002768 TI - Metabonomic characteristics and biomarker research of human lung cancer tissues by HR1H NMR spectroscopy. AB - BACKGROUND: The combination of NMR spectroscopy and multivariate data analysis (MVDA), such as orthogonal partial least squares-discriminant analysis (OPLS-DA), has been collectively acknowledged as an excellent tool to investigate tissue metabolism and provide metabolite information for the diagnosis of disease, and become an important metabonomic platform for studies in biological tissues so far. METHODS: Both ex vivo high resolution magic-angle spinning1H NMR and in vitro1H NMR spectroscopy technique were synchronously employed to analyze the metabonomic characteristics of 102 lung tissues from 34 patients with lung cancer in hope to identify potential diagnostic biomarkers for malignancy detection in lung tissues. RESULTS: Significant elevations in the levels of lipids and lactate and significant reductions in the levels of myo-inositol and valine in the cancer tissues had been identified when compared with the adjacent non-involved tissues. Furthermore, the OPLSDA models calculated by two1H NMR spectra provided for relatively high sensitivity, specificity and good prediction accuracy in the identification of class membership regardless of the number of metabolites involved. CONCLUSIONS: MVDA in combination with1H NMR spectra highlighted the potential of metabonomics in clinical settings so that the techniques might be further exploited for future lung cancer biomarker research or identification. PMID- 27002769 TI - Significance of CD99 expression in T-lineage acute lymphoblastic leukemia. AB - BACKGROUND: CD99 was first isolated as an antigen on the T acute lymphoblastic leukemia cells. It has been shown to participate in T cell adhesion and is widely expressed on a variety of hematopoietic and non-hematopoietic cell types. AIM OF WORK: Detection of the expression pattern of CD99 on leukemic and normal T cells and assessing the possibility of its use as a tool for the diagnosis and monitoring of T-ALL cases. METHODOLOGY: We used flow cytometry technique to determine the expression level of CD99 in 62 newly diagnosed T-ALL patients. Patients were followed up for the presence of minimal residual disease on day 15 and day 42 post-therapy. 20 age and sex matched healthy controls were enrolled in our study. RESULTS: CD99 was expressed in all T-ALL patients, with a higher median expression level when compared to controls (58.5% versus 1.38%, p< 0.001). On day 42 post-therapy, 100% of follow up patients who had initial CD99 expression <= 50% had no minimal residual disease, while only 45.5% of those who had initial CD99 expression > 50% had no minimal residual disease (P= 0.03). There was no significant influence of CD99 expression on the 1-year overall survival probability (P= 0.82). CONCLUSION: CD99 could be used to complement current strategy relying on TdT for diagnosis and monitoring of minimal residual disease during the post-therapy follow up of T-ALL patients. Further studies are needed to confirm these findings. PMID- 27002770 TI - Exposure to violence and psychological well-being over time in children affected by HIV/AIDS in South Africa and Malawi. AB - Many of the risk factors for violence against children are particularly prevalent in families and communities affected by HIV/AIDS. Yet, in sub-Saharan Africa, where HIV rates are high, efforts to prevent or address violence against children and its long-lasting effects are hampered by a lack of evidence. We assessed the relationship between violence exposure and mental health among HIV-affected children attending community-based organisations in South Africa (n = 834) and Malawi (n = 155, total sample n = 989) at baseline and 12-15-month follow-up. Exposure to violence in the home and in the community was high. HIV-negative children who lived with an HIV-positive person experienced most violence overall, followed by HIV-positive children. Children unaffected by HIV experienced least violence (all p < .05). Interpersonal violence in the home predicted child depression (beta = 0.17, p < .001), trauma symptoms (beta = 0.17, p < .001), lower self-esteem (beta = -0.17, p < .001), and internalising and externalising behavioural problems (beta = 0.07, p < .05), while exposure to community violence predicted trauma symptoms (beta = 0.16, p < .001) and behavioural problems (beta = 0.07, p < .05). Harsh physical discipline predicted lower self-esteem (beta = 0.18, p < .001) and behavioural problems for children (beta = 0.24, p < .001). Exposure to home (OR: 1.89, 95% CI: 1.23-2.85) and community violence predicted risk behaviour (OR: 2.39, 95% CI: 1.57-3.62). Over time, there was a decrease in depressed mood and problem behaviours, and an increase in self-esteem for children experiencing different types of violence at baseline. This may have been due to ongoing participation in the community-based programme. These data highlight the burden of violence in these communities and possibilities for programmes to include violence prevention to improve psychosocial well-being in HIV-affected children. PMID- 27002771 TI - A rehabilitation model as key to comprehensive care in the era of HIV as a chronic disease in South Africa. AB - In the era of widespread access to antiretroviral therapy, people living with HIV survive; however, this comes with new experiences of comorbidities and HIV related disability posing new challenges to rehabilitation professionals and an already fragile health system in Southern Africa. Public health approaches to HIV need to include not only prevention, treatment and support but also rehabilitation. While some well-resourced countries have developed rehabilitation approaches for HIV, resource-poor settings of Southern Africa lack a model of care that includes rehabilitation approaches providing accessible and comprehensive care for people living with HIV. In this study, a learning in action approach was used to conceptualize a comprehensive model of care that addresses HIV-related disability and a feasible rehabilitation framework for resource-poor settings. The study used qualitative methods in the form of a focus group discussion with thirty participants including people living with HIV, the multidisciplinary healthcare team and community outreach partners at a semi-rural health facility in South Africa. The discussion focused on barriers and enablers of access to rehabilitation. Participants identified barriers at various levels, including transport, physical access, financial constraints and poor multi stakeholder team interaction. The results of the group discussions informed the design of an inclusive model of HIV care. This model was further informed by established integrated rehabilitation models. Participants emphasized that objectives need to respond to policy, improve access to patient-centered care and maintain a multidisciplinary team approach. They proposed that guiding principles should include efficient communication, collaboration of all stakeholders and leadership in teams to enable staff to implement the model. Training of professional staff and lay personnel within task-shifting approaches was seen as an essential enabler to implementation. The health facility as well as outreach services such as intermediate clinics, home-based care, outreach and community based rehabilitation was identified as important structures for potential rehabilitation interventions. PMID- 27002773 TI - Visible-Light-Driven Photocatalytic Activation of Inert Sulfur Ylides for 3-Acyl Oxindole Synthesis. AB - Bicarbonyl-substituted sulfur ylide is a useful, but inert reagent in organic synthesis. Usually, harsh reaction conditions are required for its transformation. For the first time, it was demonstrated that a new, visible-light photoredox catalytic annulation of sulfur ylides under extremely mild conditions, permits the synthesis of oxindole derivatives in high selectivities and efficiencies. The key to its success is the photocatalytic single-electron transfer (SET) oxidation of the inert amide and acyl-stabilized sulfur ylides to reactive radical cations, which easily proceeds with intramolecular C-H functionalization to give the final products. PMID- 27002772 TI - Depression and HIV risk among men who have sex with men in Tanzania. AB - Studies have shown high rates of depression among men who have sex with men (MSM) in developed countries. Studies have also shown association between depression and HIV risk among MSM. However, very little research has been done on depression among African MSM. We assessed depression and HIV risk among a sample of MSM in Tanzania. We reviewed data on 205 MSM who were recruited from two Tanzanian cities using the respondent driven sampling method. Demographic and behavioral data were collected using a structured questionnaire. HIV and sexually transmitted infections data were determined from biological tests. Depression scores were assessed using the Patient Health Questionnaire (PHQ-9). For the analysis, depression scores were dichotomized as depressed (PHQ > 4) and not depressed (PHQ <= 4). Bivariate and multivariable Poisson regression analyses were conducted to assess factors associated with depression. The prevalence of depression in the sample was 46.3%. The mean (+/-SD) age of the sample was 25 (+/ 5) years. In bivariate analysis, depression was associated with self-identifying as gay (p = .001), being HIV positive (p < .001: <8% of MSM knew they were HIV infected) and having a high number of sexual partners in the last 6 months (p = .001). Depression was also associated with sexual (p = .007), physical (p = .003) and verbal (p < .001) abuse. In the Poisson regression analysis, depression was associated with verbal abuse (APR = 1.91, CI = 1.30-2.81). Depression rates were high among MSM in Tanzania. It is also associated with abuse, HIV and HIV risk behaviors. Thus, reducing the risk of depression may be helpful in reducing the risk of HIV among MSM in Africa. We recommend the colocation of mental health and HIV preventive services as a cost-effective means of addressing both depression and HIV risk among MSM in Africa. PMID- 27002774 TI - Transfer of multivariate regression models between high-resolution NMR instruments: application to authenticity control of sunflower lecithin. AB - In recent years the number of spectroscopic studies utilizing multivariate techniques and involving different laboratories has been dramatically increased. In this paper the protocol for calibration transfer of partial least square regression model between high-resolution nuclear magnetic resonance (NMR) spectrometers of different frequencies and equipped with different probes was established. As the test system previously published quantitative model to predict the concentration of blended soy species in sunflower lecithin was used. For multivariate modelling piecewise direct standardization (PDS), direct standardization, and hybrid calibration were employed. PDS showed the best performance for estimating lecithin falsification regarding its vegetable origin resulting in a significant decrease in root mean square error of prediction from 5.0 to 7.3% without standardization to 2.9-3.2% for PDS. Acceptable calibration transfer model was obtained by direct standardization, but this standardization approach introduces unfavourable noise to the spectral data. Hybrid calibration is least recommended for high-resolution NMR data. The sensitivity of instrument transfer methods with respect to the type of spectrometer, the number of samples and the subset selection was also discussed. The study showed the necessity of applying a proper standardization procedure in cases when multivariate model has to be applied to the spectra recorded on a secondary NMR spectrometer even with the same magnetic field strength. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27002775 TI - Periimplant Bone Response in Human-Retrieved, Clinically Stable, Successful, and Functioning Dental Implants After a Long-Term Loading Period: A Report of 17 Cases From 4 to 20 Years. AB - OBJECTIVE: This study aimed at a histologic and histomorphometric analysis of the periimplant tissues and bone-titanium interface reactions in successfully osseointegrated, clinically stable, and immobile human titanium dental implants retrieved after a long loading period. MATERIALS AND METHODS: In the last 30 months (2013-2015), 21 implants, retrieved from individuals for different causes after a loading period ranging from 4 to 20 years, were sent to the Implant Retrieval Center, University of Chieti-Pescara, Italy. In 4 cases, almost all the bone had been lost during the retrieval, whereas in the remaining 17 cases, mineralized bone was still present. RESULTS: Around the majority of the implants, mature compact bone with few marrow spaces was found. The trabecular bone, constituted by a few thin bone trabeculae, was in a periimplant location around only a few implants. A high percentage of bone-implant contact (BIC) (comprised between 32 +/- 4.1% and 83 +/- 2.9%) was present. In almost all implants, the space within the threads was almost completely filled by compact lamellar bone or by a thin layer of bone. Close and tight contact between bone and implant surface was observed in all specimens with no gaps or connective tissue at the interface. CONCLUSIONS: All implants appeared to be well integrated in the surrounding mineralized bone, and all of them showed adequate bone-to-implant contact percentages. PMID- 27002776 TI - The Use of Dental Implants in Organ Transplant Patients Undergoing Immunosuppressive Therapy: An Overview of Publications. AB - INTRODUCTION: Immunosuppressive treatment has been commonly considered a contraindication to the use of dental implants. This article is aimed at analyzing the publications related to that issue and answering the question of whether such treatment is viable in patients with organ transplants. MATERIALS AND METHODS: The following databases have been searched to find related publications: Clinical Key, Web of Science, Up to date, PubMed, and Medline. Full research paper texts published over the past 15 years have been taken into consideration. The selected publications were divided depending on the type of study material, that is, whether they focused on animal tests or human tests. RESULTS: The studies performed on animals showed negative impact of immunosuppression on the bones surrounding the implants. Publications presenting clinical cases of organ transplant patients indicated no significant disorders in the process of implant osseointegration despite the use of immunosuppressive drugs. CONCLUSIONS: Despite the negative impact of immunosuppressive drugs on the process of bone healing, it is possible to treat organ transplant patients with intraosseous titanium implants. The key to success is the observance of appropriate treatment procedures and proper hygienic routines. An alteration of medication regimen that currently makes use of immunosuppressive drugs of much lower toxicity is also extremely significant. PMID- 27002777 TI - Call for Implementing a Radiation Protection Culture in Fluoroscopically Guided Interventional Procedures. AB - OBJECTIVE: The purpose of this article is to discuss the first prospective study published to date that followed a large cohort of radiologic technologists; the authors examined the risks of cancer incidence and mortality in U.S. radiologic technologists (radiographers) assisting in fluoroscopically guided interventional procedures. CONCLUSION: There is an urgent need for implementing a radiation protection culture for medical procedures that use ionizing radiation. PMID- 27002778 TI - Production of a novel bioflocculant and its flocculation performance in aluminum removal. AB - A novel bioflocculant CBF with high flocculating activity, produced by mixed culture of Rhizobium radiobacter F2 and Bacillus sphaericus F6 from soil, was investigated with regard to its production and flocculation performance in Al(III) removal. The most preferred carbon source, nitrogen source and C/N ratio (w/w) for strains F2 and F6 to produce CBF were glucose, urea and 20, respectively. The optimal inoculum size for CBF production was 10 % (v/v). The optimal initial pH, culture temperature and shaking speed were 7-8, 30 degrees C and 140 r/min for 24 h, respectively, under which the flocculating activity of the bioflocculant reached 98.52 %. According to literature review, flocculant dosage, coagulant aid dosage, pH, hydraulic condition of coagulation and sedimentation time are considered as influencing parameters for CBF flocculation performance in Al(III) removal by L16(4(5)) orthogonal design. The optimal conditions for Al(III) removal obtained through analysis and verification experiments were as follows: CBF, 28 mg/L; coagulant aid, 1.5 mL/L; initial pH, 8.0; and hydraulic conditions of coagulation: stir speed, 160 r/min; stir time, 40 s; and sedimentation time, 30 min. Under the optimal conditions, the removal efficiency of Al(III) was 92.95 %. Overall, these findings indicate that bioflocculant CBF offers an effective alternative method of decreasing Al(III) during drinking water treatment. PMID- 27002780 TI - Head and Neck Cancer Survivorship Care Guideline. PMID- 27002779 TI - Exposure to multiple languages enhances communication skills in infancy. AB - Early exposure to multiple languages can enhance children's communication skills, even when children are effectively monolingual (Fan, Liberman, Keysar & Kinzler, ). Here we report evidence that the social benefits of multilingual exposure emerge in infancy. Sixteen-month-old infants participated in a communication task that required taking a speaker's perspective to understand her intended meaning. Infants were presented with two identical toys, such as two cars. One toy was mutually visible to both the infant and the speaker, but the other was visible only to the infant and was blocked from the speaker's view by an opaque barrier. The speaker requested the mutually visible toy and we evaluated whether infants understood the speaker's request. Whereas monolingual infants were at chance in choosing between the two toys, infants with multilingual exposure reliably chose the toy the speaker requested. Successful performance was not related to the degree of exposure to other languages, suggesting that even minimal multilingual exposure may enhance communication skills. PMID- 27002781 TI - The Effects of Fluvoxamine on the Steady-State Plasma Concentrations of Escitalopram and Desmethylescitalopram in Depressed Japanese Patients. AB - BACKGROUND: The aim of this study was to determine the impact of fluvoxamine, an inhibitor of Cytochrome P450 (CYP) 2C19 (CYP2C19), on the pharmacokinetics of escitalopram, a substrate of CYP2C19. METHODS: Thirteen depressed patients initially received a 20-mg/d dose of escitalopram alone. Subsequently, a 50-mg/d dose of fluvoxamine was administered because of the insufficient efficacy of escitalopram. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using high-performance liquid chromatography before and after fluvoxamine coadministration. The QT and corrected QT (QTc) intervals were measured before and after fluvoxamine coadministration. RESULTS: Fluvoxamine significantly increased the plasma concentrations of escitalopram (72.3 +/- 36.9 ng/mL versus 135.2 +/- 79.7 ng/mL, P < 0.01) but not those of desmethylescitalopram (21.5 +/- 7.0 ng/mL versus 24.9 +/- 12.0 ng/mL, no significance [ns]). The ratios of desmethylescitalopram to escitalopram were significantly decreased during fluvoxamine coadministration (0.37 +/- 0.21 versus 0.21 +/- 0.10, P < 0.01). The CYP2C19 genotype did not fully explain the degree of the change. Fluvoxamine coadministration did not change the QT or QTc intervals. CONCLUSIONS: The results of this study suggest that adjunctive treatment with fluvoxamine increases the concentration of escitalopram. The QTc interval did not change in this condition. PMID- 27002782 TI - Interventions for Cardiovascular Patients with Type D Personality: A Systematic Review. AB - BACKGROUND: Cardiovasculardisease (CVD) is a major cause of death worldwide. Type D personality, a newly identified risk factor for cardiac outcomes, can deteriorate the health outcomes of CVD patients. Several interventional studies have been conducted on CVD patients with type D personality. AIM: To provide the best available evidence of the effects and characteristics of interventions applied to cardiac patients with type D personality. METHODS: Experimental studies on the effects of interventions for cardiac patients with type D personality were reviewed. English and Chinese electronic databases were searched from inception to December 2014. The eligibility and quality of each article were reviewed by two independent reviewers. The outcomes of interest included psychological health (anxiety & depression), physical functioning, and quality of life. Data were synthesized in a narrative form rather than meta-analysis because of the heterogeneity of studies and the insufficient data for statistical pooling. RESULTS: Four studies (one randomized controlled trial and three single group pre- and posttests) involving 967 cardiac patients were identified. The quality of included studies was moderate, with three studies rated as fair and one study rated as poor. Cardiac rehabilitation programs were the interventions identified in all the included studies, with main components of physical exercise, patient education, psychological intervention, and individual counseling. The findings of this review indicated that cardiac rehabilitation can significantly reduce anxiety and depression, improve physical functioning, and quality of life in cardiac patients with type D personality. The evidence of optimal duration, frequency of interventions, and length of each session was not established. LINKING EVIDENCE TO ACTION: This review provides preliminary evidence for the use of cardiac rehabilitation as an effective intervention to improve health outcomes in cardiac patients with type D personality. The optimal delivery format of the intervention for cardiac patients with type D personality needs to be explored. PMID- 27002783 TI - Opioid overdose and naloxone education in a substance use disorder treatment program. AB - BACKGROUND AND OBJECTIVES: Opioid users in treatment are at high risk of relapse and overdose, making them an important target for efforts to reduce opioid overdose mortality. Overdose Education (OE) is one such intervention, and this study tests the effectiveness of OE in a community substance use disorder treatment program. METHODS: Opioid users were recruited from a community treatment center for the study. The Opioid Overdose Knowledge Scale (OOKS) was administered before and after an educational intervention (small group lecture, slideshow, and handout based on previously published content) to assess knowledge of the risks, signs, and actions associated with opioid overdose, including use of naloxone. Additional survey questions assessed naloxone access, naloxone education, and overdose experiences at treatment and 3-month follow-up. Subjects (n = 43) were 28% female and had a mean age of 31 years. OOKS scores were compared at pre-intervention, post-intervention, and follow-up, and results were also compared with a historical non-intervention control group (n = 14). RESULTS: Total score on the OOKS increased significantly from pre- to post-education, and improvement was maintained at follow-up (p < .0001). OOKS subdomains of actions and naloxone use also had significant increases (p < .0001). Four subjects reported possessing naloxone in the past, and only one subject who did not already have naloxone at the time of treatment had obtained it at follow-up. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Education about opioid overdose and naloxone use in a community treatment program increases overdose knowledge, providing support for the idea of making OE a routine part of substance use disorder treatment. However, the rate of follow through on accessing naloxone was low with this education-only intervention. PMID- 27002785 TI - 'Tandem balloon tamponade' for arterial bleeding from the uterine fundus: two case reports. PMID- 27002786 TI - Amphiphobic Polytetrafluoroethylene Membranes for Efficient Organic Aerosol Removal. AB - Polytetrafluoroethylene (PTFE) membrane is an extensively used air filter, but its oleophilicity leads to severe fouling of the membrane surface due to organic aerosol deposition. Herein, we report the fabrication of a new amphiphobic 1H,1H,2H,2H-perfluorodecyl acrylate (PFDAE)-grafted ZnO@PTFE membrane with enhanced antifouling functionality and high removal efficiency. We use atomic layer deposition (ALD) to uniformly coat a layer of nanosized ZnO particles onto porous PTFE matrix to increase surface area and then subsequently graft PFDAE with plasma. Consequently, the membrane surface showed both superhydrophobicity and oleophobicity with a water contact angle (WCA) and an oil contact angle (OCA) of 150 degrees and 125 degrees , respectively. The membrane air permeation rate of 513 (m(3) m(-2) h(-1) kPa(-1)) was lower than the pristine membrane rate of 550 (m(3) m(-2) h(-1) kPa(-1)), which indicates the surface modification slightly decreased the membrane air permeation. Significantly, the filtration resistance of this amphiphobic membrane to the oil aerosol system was much lower than the initial one. Moreover, the filter exhibited exceptional organic aerosol removal efficiencies that were greater than 99.5%. These results make the amphiphobic PTFE membranes very promising for organic aerosol-laden air-filtration applications. PMID- 27002788 TI - Magnesia-Based Cements: A Journey of 150 Years, and Cements for the Future? AB - This review examines the detailed chemical insights that have been generated through 150 years of work worldwide on magnesium-based inorganic cements, with a focus on both scientific and patent literature. Magnesium carbonate, phosphate, silicate-hydrate, and oxysalt (both chloride and sulfate) cements are all assessed. Many such cements are ideally suited to specialist applications in precast construction, road repair, and other fields including nuclear waste immobilization. The majority of MgO-based cements are more costly to produce than Portland cement because of the relatively high cost of reactive sources of MgO and do not have a sufficiently high internal pH to passivate mild steel reinforcing bars. This precludes MgO-based cements from providing a large-scale replacement for Portland cement in the production of steel-reinforced concretes for civil engineering applications, despite the potential for CO2 emissions reductions offered by some such systems. Nonetheless, in uses that do not require steel reinforcement, and in locations where the MgO can be sourced at a competitive price, a detailed understanding of these systems enables their specification, design, and selection as advanced engineering materials with a strongly defined chemical basis. PMID- 27002789 TI - Expedient Route To Access Rare Deoxy Amino l-Sugar Building Blocks for the Assembly of Bacterial Glycoconjugates. AB - Bacterial glycoproteins and oligosaccharides contain several rare deoxy amino l sugars which are virtually absent in the human cells. This structural difference between the bacterial and host cell surface glycans can be exploited for the development of carbohydrate based vaccines and target specific drugs. However, the unusual deoxy amino l-sugars present in the bacterial glycoconjugates are not available from natural sources. Thus, procurement of orthogonally protected rare l-sugar building blocks through efficient chemical synthesis is a crucial step toward the synthesis of structurally well-defined and homogeneous complex glycans. Herein, we report a general and expedient methodology to access a variety of unusual deoxy amino l-sugars starting from readily available l rhamnose and l-fucose via highly regioselective, one-pot double serial and double parallel displacements of the corresponding 2,4-bistriflates using azide and nitrite anions as nucleophiles. Alternatively, regioselective monotriflation at O2, O3, and O4 of l-rhamnose/l-fucose allowed selective inversions at respective positions leading to diverse rare sugars. The orthogonally protected deoxy amino l-sugar building blocks could be stereoselectively assembled to obtain biologically relevant bacterial O-glycans, as exemplified by the first total synthesis of the amino linker-attached, conjugation-ready tetrasaccharide of O-PS of Yersinia enterocolitica O:50 strain 3229 and the trisaccharide of Pseudomonas chlororaphis subsp. aureofaciens strain M71. PMID- 27002790 TI - Experimental and Theoretical Investigation of a Series of Novel Dimanganese(III) MU-Hydroxo Bisporphyrins: Magneto-Structural Correlation and Effect of Metal Spin on Porphyrin Core Deformation. AB - The synthesis, structure, and properties of a new family of five ethane-bridged dimanganese(III) MU-hydroxo bisporphyrins with the same core structure but different counteranions are reported here. Additions of 10% Bronsted acids such as HI, HBF4, HSbF6, HPF6, and HClO4 to a dichloromethane solution of the dichloro dimanganese(III) bisporphyrin produces complexes having a remarkably bent MU hydroxo group with I3(-), BF4(-), SbF6(-), PF6(-), and ClO4(-) as counteranions, respectively. The X-ray structures of all complexes have been determined, which have revealed the presence of two equivalent high-spin manganese(III) centers with equally distorted porphyrin rings in the complexes, in sharp contrast with the case for the diiron(III) MU-hydroxo bisporphyrin analogues. (1)H NMR spectra have shown highly deshielded meso resonances, unlike the case for the diiron(III) analogues, where the meso resonances are highly shielded. The variable temperature magnetic data have been subjected to a least-squares fit which provides a moderate antiferromagnetic coupling through the hydroxo bridge between two zero-field split Mn(III) centers with coupling constant (J) values ranging from -29.5 to -38.6 cm(-1). Fairly good correlations are observed for J with Mn O(H) distances and Mn-O(H)-Mn angles for all the complexes except for that having an I3(-) counteranion. DFT calculations support the stabilization of two equivalent high-spin Mn(III) porphyrin cores in the complexes and have also explored the role of metal spin in controlling porphyrin ring deformation. Unlike diiron(III) MU-hydroxo bisporphyrin complexes, the dimanganese(III) analogues do not have easily accessible spin states of the metal attainable by subtle environmental perturbations and, therefore, can only stabilize the high-spin state with a variety of counteranions. PMID- 27002791 TI - Caring for Premature Life and Death: The Relational Dynamics of Detachment in a NICU. AB - Drawing on fieldwork in a neonatal intensive care unit (NICU) in Chiang Mai during 2010 and 2012, I examine neonatal care as a contingent entanglement of technological and ethical relationships with vulnerable others. Along the continuum of universal antenatal and delivery care, neonatal medicine becomes a normative part of reproductive health care in Chiang Mai. As the NICU opens its door to sick newborns whose belonging to kinship and the nation-state is uncertain, neonatal care requires deliberate practices to incorporate them into life-sustaining connections. By tracing medical staff's effort to be accountable to their fragile patients, I show that withdrawing of intensive care is relational work that requires affective involvement and distancing through commensality, prosthetic extensions, and karmic network. This specific mode of care, which is premised on the combination of unconditional openness and careful detachment, offers insight into a possible enactment of hospitality within biomedical institutions. PMID- 27002787 TI - Multiple myeloma in the marrow: pathogenesis and treatments. AB - Multiple myeloma (MM) is a B cell malignancy resulting in osteolytic lesions and fractures. In the disease state, bone healing is limited owing to increased osteoclastic and decreased osteoblastic activity, as well as an MM-induced forward-feedback cycle where bone-embedded growth factors further enhance tumor progression as bone is resorbed. Recent work on somatic mutation in MM tumors has provided insight into cytogenetic changes associated with this disease; the initiating driver mutations causing MM are diverse because of the complexity and multitude of mutations inherent in MM tumor cells. This manuscript provides an overview of MM pathogenesis by summarizing cytogenic changes related to oncogenes and tumor suppressors associated with MM, reviewing risk factors, and describing the disease progression from monoclonal gammopathy of undetermined significance to overt MM. It also highlights the importance of the bone marrow microenvironment (BMM) in the establishment and progression of MM, as well as associated MM-induced bone disease, and the relationship of the bone marrow to current and future therapeutics. This review highlights why understanding the basic biology of the healthy and diseased BMM is crucial in the quest for better treatments and work toward a cure for genetically diverse diseases such as MM. PMID- 27002792 TI - Access to 1,2,3,4-Tetraoxygenated Benzenes via a Double Baeyer-Villiger Reaction of Quinizarin Dimethyl Ether: Application to the Synthesis of Bioactive Natural Products from Antrodia camphorata. AB - The first systematic investigation into the Baeyer-Villiger reaction of an anthraquinone is presented. The double Baeyer-Villiger reaction of quinizarin dimethyl ether is viable, directly providing the dibenzo[b,f][1,4]-dioxocin-6,11 dione ring-system, which is otherwise difficult to prepare. This methodology provides rapid access to 1,2,3,4-tetraoxygenated benzenes, and has been exploited by application to the total synthesis of a natural occurring benzodioxole and its biphenyl dimer, which both display noteworthy biological activity. Interestingly, the axially chiral biphenyl was found to be configurationally stable, but the resolved enantiomers exhibit no optical activity at the alphaD-line. PMID- 27002794 TI - Investigating the Reactivity of 1,4-Anthracene-Incorporated Cycloparaphenylene. AB - Cycloparaphenylenes (CPPs) and their derivatives are unique conjugated macrocycles with novel optoelectronic and host-guest properties. A better understanding of their reactivity is essential for creating new functional materials utilizing these strained aromatic molecules as building blocks. 1,4 Anthracene-incorporated CPP 1 was synthesized and exhibited Diels-Alder reactivity but was unable to photodimerize. Comparison studies with cyclophane 2 and unstrained 3 indicated that the distorted anthracene geometry is likely the major contributor to the anomalous reactivity of 1. PMID- 27002795 TI - The Relationship Between Whole-Body External Loading and Body-Worn Accelerometry During Team-Sport Movements. AB - PURPOSE: To investigate the relationship between whole-body accelerations and body-worn accelerometry during team-sport movements. METHODS: Twenty male team sport players performed forward running and anticipated 45 degrees and 90 degrees side-cuts at approach speeds of 2, 3, 4, and 5 m/s. Whole-body center-of mass (CoM) accelerations were determined from ground-reaction forces collected from 1 foot-ground contact, and segmental accelerations were measured from a commercial GPS accelerometer unit on the upper trunk. Three higher-specification accelerometers were also positioned on the GPS unit, the dorsal aspect of the pelvis, and the shaft of the tibia. Associations between mechanical load variables (peak acceleration, loading rate, and impulse) calculated from both CoM accelerations and segmental accelerations were explored using regression analysis. In addition, 1-dimensional statistical parametric mapping (SPM) was used to explore the relationships between peak segmental accelerations and CoM acceleration profiles during the whole foot-ground contact. RESULTS: A weak relationship was observed for the investigated mechanical load variables regardless of accelerometer location and task (R2 values across accelerometer locations and tasks: peak acceleration .08-.55, loading rate .27-.59, and impulse .02-.59). Segmental accelerations generally overestimated whole-body mechanical load. SPM analysis showed that peak segmental accelerations were mostly related to CoM accelerations during the first 40-50% of contact phase. CONCLUSIONS: While body-worn accelerometry correlates to whole-body loading in team-sport movements and can reveal useful estimates concerning loading, these correlations are not strong. Body-worn accelerometry should therefore be used with caution to monitor whole-body mechanical loading in the field. PMID- 27002793 TI - Vaccination of adults with 23-valent pneumococcal polysaccharide vaccine induces robust antibody responses against pneumococcal serotypes associated with serious clinical outcomes. AB - PNEUMOVAXTM 23, a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates recovered from adult cases of invasive pneumococcal disease. Several studies have demonstrated that pneumococcal serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A are associated with higher case-fatality or meningitis rates than other pneumococcal serotypes. This study (U05-PnPS-403; EudraCT: 2008-003648-12) evaluated the immune response followings administration of PPV23 for 4 of these serotypes (10A, 11A, 15B, and 17F), that are included in PPV23 but not in licensed pneumococcal conjugate vaccines. Serotype-specific IgG geometric mean concentrations (GMCs) and geometric mean fold-rises (GMFRs) for these 4 serotypes were measured by a validated enzyme-linked immunosorbent assay (ELISA) in 104 subjects >50 y of age who were enrolled in a study evaluating the safety and immunogenicity of a single-dose of PPV23. At 1 month post-vaccination, GMCs for serotypes10A, 11A, 15B and 17F were 6.5, 4.3, 14.7, and 5.1 ug/mL, respectively. GMFRs from baseline were 9.0, 4.5, 8.4, and 11.5, respectively. The percentages of subjects achieving >2-fold increases in IgG GMCs between pre vaccination and 1 month post-vaccination were 90%, 85%, 88% and 89%, respectively. In conclusion, PPV23 induces a robust immune response in adults to pneumococcal serotypes 10A, 11A, 15B, and 17F, which have been associated with elevated case-fatality or meningitis rates. PMID- 27002796 TI - Gestational Diabetes Mellitus Is Strongly Associated With Non-Alcoholic Fatty Liver Disease. AB - OBJECTIVES: Insulin resistance is central to the development of non-alcoholic fatty liver disease (NAFLD), and gestational diabetes mellitus (GDM) is an early marker of insulin resistance. We hypothesized that a history of GDM would identify women at higher risk of NAFLD in middle age. METHODS: Women from the multicenter Coronary Artery Risk Development in Young Adults (CARDIA) cohort study who delivered >=1 birth, were free of diabetes prior to pregnancy(ies), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n=1,115). History of GDM by self-report, validated in a subsample by review of antenatal glucose testing, and metabolic risk factors were assessed prospectively. NAFLD was defined by liver attenuation (LA)<=40 Hounsfield Units on CT scan after exclusion of other causes of hepatic steatosis. RESULTS: Of 1,115 women meeting selection criteria (57% black, 43% white, median age 25 years at baseline), 124 (11%) reported a history of GDM and 75 (7%) met the CT definition for NAFLD at year 25. The crude risk of NAFLD at the 25-year visit was significantly higher in women with GDM compared to those without (14 vs. 5.8%, OR: 2.56, 95% CI: 1.44-4.55, P<0.01). History of GDM remained associated with NAFLD (OR: 2.29, 95% CI: 1.23-4.27, P=0.01) after adjustment for covariates in multivariable logistic regression. Addition of incident diabetes mellitus (DM) into the final model attenuated the association between GDM and NAFLD (OR: 1.48, 95% CI: 0.73-3.02, P=0.28). CONCLUSION: GDM is a risk marker for NAFLD and represents an opportunity to identify women at risk for NAFLD at a young age and may be mediated by the development of incident DM. PMID- 27002797 TI - The Risk of Relapse after Anti-TNF Discontinuation in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. AB - OBJECTIVES: To perform a meta-analysis of the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC), to evaluate risk factors for relapse, and to assess the response to retreatment with the same anti-TNF. METHODS: Studies evaluating the incidence of relapse after anti-TNF discontinuation in patients with CD or UC who reached clinical remission with anti-TNFs were included. Bibliographies up to January 2015 were searched. Frequency of relapse after discontinuation of anti-TNF agents was determined; meta-analyses were performed using the inverse-variance method. RESULTS: We included 27 studies (21 infliximab and 6 infliximab/adalimumab). The overall risk of relapse after discontinuation of anti-TNF therapy was 44% for CD (95% confidence interval (CI) 36-51%; I(2)=79%; 912 patients) and 38% for UC (23-52%; I(2)=82%; 266 patients). In CD, the relapse rate was 38% at 6 months after discontinuation (short term), 40% at 12 months (medium term), and 49% at >25 months (long term). In UC, 28% of patients relapsed at 12 months. In CD, when clinical remission was the only criterion for stopping anti-TNF therapy, the relapse rate after 1 year was 42%, which decreased to 26% when endoscopic remission was also required. Retreatment with the same anti-TNF induced remission again in 80% of cases (68-91%). CONCLUSIONS: Approximately one-third of patients with inflammatory bowel disease in remission under anti-TNF treatment relapsed 1 year after discontinuation. This proportion increased to half in the long term. In CD patients, the risk of relapse was lower when the criterion for discontinuation was endoscopic remission and not only clinical remission. Response to retreatment with the same anti-TNF agent was favorable. PMID- 27002799 TI - Vitamin D Deficiency Is Associated With Increased Risk of Non-alcoholic Steatohepatitis in Adults With Non-alcoholic Fatty Liver Disease: Possible Role for MAPK and NF-kappaB? AB - OBJECTIVES: The objective of this study was to determine the relationship of serum vitamin D deficiency (VDD) to histologic features of non-alcoholic fatty liver disease (NAFLD), and associated demographic, clinical, laboratory, and transcriptomic data in the well-characterized Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN) cohort. METHODS: Serum vitamin D 25(OH)D (VD) was quantified by liquid chromatography-tandem mass spectrometry in 190 adults (>18 years) with biopsy-proven NAFLD. Subjects were categorized according to their level of VD as either sufficient (>30 ng/ml), insufficient (>=20<=30 ng/ml), or deficient (VDD; <20 ng/ml). Multivariable logistic regression was used to investigate the association of VDD and the presence of definite NASH and individual histological features of NAFLD after adjusting for age, sex, race, body mass index, alanine aminotransferase, and diabetes status. Hepatic transcriptomic data was compared between VDD and non-VDD subjects. RESULTS: VDD was present in 55% of subjects and was independently associated with definitive NASH (odds ratio (OR) 3.15, 95% confidence interval (CI), 1.62-6.15, P=0.001), increased lobular inflammation (OR=1.98, 95% CI, 1.08-3.61, P=0.026), more ballooning (OR=2.38, 95% CI, 1.32-4.30, P=0.004), and the presence of fibrosis (OR=2.32, 95% CI, 1.13-4.77, P=0.022). There was a significant inverse relationship between lower levels of serum resistin and increased VD level category (P=0.013). The KRT10, SEMA3B, SNORD3C, ARSD, and IGKV4-1 genes were differentially expressed (false discovery rate <0.05) between VDD and non-VDD subjects. Gene ontology and pathway analysis suggest activation of the mitogen activated protein kinase and nuclear factor-kappaB pathways in VDD NAFLD subjects. CONCLUSIONS: VDD is prevalent among US adult NAFLD patients and is independently associated with a definitive diagnosis of NASH and increased histological severity. Novel associations in proinflammatory pathways were identified, which suggest the mechanism for VDD in the pathogenesis of NASH and support dietary and/or lifestyle modifications to increase vitamin D levels in these patients. PMID- 27002800 TI - Poor Correlation Between Clinical Disease Activity and Mucosal Inflammation, and the Role of Psychological Comorbidity, in Inflammatory Bowel Disease. AB - OBJECTIVES: There is a move toward patient-reported outcome measures as end points in clinical trials of novel therapies for inflammatory bowel disease (IBD). However, the association between patient-reported symptoms and mucosal inflammation, and the influence of psychological factors, remains unclear. We examined this in a secondary care population. METHODS: Validated patient-reported disease activity indices were used to define clinically active disease in a cohort of 356 patients with ulcerative colitis (UC) or Crohn's disease (CD). A fecal calprotectin >=250 MUg/g was used to define active mucosal inflammation. The hospital anxiety and depression scale (HADS) and patient health questionnaire (PHQ)-15 were used to assess for anxiety, depression, or somatization, respectively. Logistic regression analysis was performed to determine the association between symptoms, mucosal inflammation, and psychological comorbidity. RESULTS: Clinical disease activity was associated with mucosal inflammation in UC (odds ratio (OR) 3.36; 95% confidence interval (CI) 1.34-8.47) but not in CD (OR 1.69; 95% CI 0.74-3.83). Depression in UC (OR 1.21 per 1-point increase in HADS; 95% CI 1.02-1.44) and somatization in UC (OR 1.17 per 1-point increase in PHQ-15; 95% CI 1.03-1.33) and CD (OR 1.31 per 1-point increase in PHQ 15; 95% CI 1.13-1.52) were associated with clinical disease activity. Overall, patient-reported symptoms yielded poor positive predictive values for mucosal inflammation in both CD and UC. CONCLUSIONS: Patient-reported symptoms and the Harvey-Bradshaw index were poor predictors of mucosal inflammation in CD. Psychological comorbidity was associated with gastrointestinal symptom-reporting. A shift in the focus of IBD management toward one addressing both psychological and physical well-being is required. PMID- 27002798 TI - Novel 3D Magnetic Resonance Elastography for the Noninvasive Diagnosis of Advanced Fibrosis in NAFLD: A Prospective Study. AB - OBJECTIVES: Recent studies show two-dimensional (2D)-magnetic resonance elastography (MRE) is accurate in diagnosing advanced fibrosis (stages 3 and 4) in nonalcoholic fatty liver disease (NAFLD) patients. Three-dimensional (3D)-MRE is a more advanced version of the technology that can image shear-wave fields in 3D of the entire liver. The aim of this study was to prospectively compare the diagnostic accuracy of 3D-MRE and 2D-MRE for diagnosing advanced fibrosis in patients with biopsy-proven NAFLD. METHODS: This cross-sectional analysis of a prospective study included 100 consecutive patients (56% women) with biopsy proven NAFLD who also underwent MRE. Area under the receiver operating characteristic (AUROC) analysis was performed to assess the accuracy of 2D- and 3D-MRE in diagnosing advanced fibrosis. RESULTS: The mean (+/-s.d.) of age and body mass index were 50.2 (+/-13.6) years and 32.1 (+/-5.0) kg/m(2), respectively. The AUROC for diagnosing advanced fibrosis was 0.981 for 3D-MRE at 40 Hz, 0.927 for 3D-MRE at 60 Hz (standard shear-wave frequency), and 0.921 for 2D-MRE at 60 Hz (standard shear-wave frequency). At a threshold of 2.43 kPa, 3D MRE at 40 Hz had sensitivity 1.0, specificity 0.94, positive predictive value 0.72, and negative predictive value 1.0 for diagnosing advanced fibrosis. 3D-MRE at 40 Hz had significantly higher AUROC (P<0.05) than 2D-MRE at 60 Hz for diagnosing advanced fibrosis. CONCLUSIONS: Utilizing a prospective study design, we demonstrate that 3D MRE at 40 Hz has the highest diagnostic accuracy in diagnosing NAFLD advanced fibrosis. Both 2D- and 3D-MRE at 60 Hz, the standard shear-wave frequency, are also highly accurate in diagnosing NAFLD advanced fibrosis. PMID- 27002801 TI - Duration of Inflammatory Bowel Disease Is Associated With Increased Risk of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis and IBD. AB - OBJECTIVES: Primary sclerosing cholangitis (PSC) often coexists with inflammatory bowel disease (IBD) and can be complicated by cholangiocarcinoma (CCA), a lethal malignancy for which reliable predictors remain unknown. We aimed to characterize the influence of colectomy and IBD duration on risk of CCA in patients with PSC IBD. METHODS: A retrospective review of patients with PSC-IBD seen at the Mayo Clinic, Rochester, between January 2005 and May 2013 was performed. The primary outcome was time to development of CCA and our goal was to determine whether the risk differed between patients with and without colectomy. Risk factors were assessed using univariable and multivariable Cox proportional hazard models where colectomy, IBD disease duration, and development of advanced liver disease were treated as time-dependent covariates. RESULTS: A total of 399 patients with PSC IBD were included in the study, of whom 137 had a colectomy and 123 patients developed CCA. Age-adjusted univariate Cox proportional hazard models demonstrated that colectomy (hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.05-2.22, P=0.02) and duration of IBD (HR 1.37, 95% CI 1.15-1.63, P<0.01) were associated with an increased risk of CCA, and colonic neoplasia (HR 1.52, 95% CI 0.97-2.37, P=0.06) and colectomy for colonic neoplasia (HR 1.62, 95% CI 1.01 2.61, P=0.05) approached significance. Among patients with a history of colectomy, colonic neoplasia as the indication for surgery was associated with a particularly increased risk of CCA (HR 2.91, 95% CI 1.24-6.84, P=0.01) compared with medically refractory disease. On multivariate analysis, duration of IBD remained significantly associated with CCA (HR 1.33, 95% CI 1.11-1.60, P<0.01). The influence of IBD duration on CCA risk was not modified after colectomy (P=0.69). CONCLUSIONS: Prolonged duration of IBD is associated with an increased risk of CCA in patients with PSC-IBD, and colectomy itself does not modify this risk. These findings identify a subset of patients who are at high risk of this lethal complication and in need of close surveillance. PMID- 27002803 TI - The role of glucocorticoid receptors in metabolic syndrome and psychiatric illness. AB - Glucocorticoids (GCs) are involved in a large number of the physiological changes associated with metabolic syndrome and certain psychiatric illness. Although significance is often given to the concentration of GC, its biological action is determined by the activation of intracellular GC receptors (GR). Genetic polymorphisms of the GR and the large array of GR related cofactors can directly or indirectly affect the pathophysiology and evolution of these conditions. This review will discuss the effects of GR mutations on metabolic syndrome and psychotic depression. PMID- 27002804 TI - In Memoriam - Prof. G. Barry Pierce (1925-2015). PMID- 27002802 TI - African Americans Have Better Outcomes for Five Common Gastrointestinal Diagnoses in Hospitals With More Racially Diverse Patients. AB - OBJECTIVES: We sought to characterize the relationship between hospital inpatient racial diversity and outcomes for African-American patients including rates of major complications or mortality during hospitalization for five common gastrointestinal diagnoses. METHODS: Using the 2012 National Inpatient Sample database, hospital inpatient racial diversity was defined as the percentage of African-American patients discharged from each hospital. Logistic regression was used to predict major complication rates or death, long length of stay, and high total charges. Control variables included age, gender, payer type, patient location, area-associated income quartile, hospital characteristics including size, urban vs. rural, teaching vs. nonteaching, region, and the interaction of the percentage of African Americans with patient race. RESULTS: There were 848,395 discharges across 3,392 hospitals. The patient population was on average 27% minority (s.d.+/-21%) with African Americans accounting for 14% of all patients. Overall, African-American patients had higher rates of major complications or death relative to white patients (adjusted odds ratio (aOR) 1.19; 95% confidence interval (CI) 1.16-1.23). However, when treated in hospitals with higher patient racial diversity, African-American patients experienced significantly lower rates of major complications or mortality (aOR 0.80; 95% CI 0.74-0.86). CONCLUSIONS: African Americans have better outcomes for five common gastrointestinal diagnoses when treated in hospitals with higher inpatient racial diversity. This has major ramifications on total hospital charges. PMID- 27002805 TI - Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey. AB - Claudins are major constituents of tight junctions, contributing both to their intercellular sealing and selective permeability properties. While claudins and claudin-like molecules are present in some invertebrates, the association of claudins with tight junctions has been conclusively documented only in vertebrates. Here we report the sequencing, phylogenetic analysis and comprehensive spatiotemporal expression analysis of the entire claudin gene family in the basal extant vertebrate, the sea lamprey. Our results demonstrate that clear orthologues to about half of all mammalian claudins are present in the lamprey, suggesting that at least one round of whole genome duplication contributed to the diversification of this gene family. Expression analysis revealed that claudins are expressed in discrete and specific domains, many of which represent vertebrate-specific innovations, such as in cranial ectodermal placodes and the neural crest; whereas others represent structures characteristic of chordates, e.g. pronephros, notochord, somites, endostyle and pharyngeal arches. By comparing the embryonic expression of claudins in the lamprey to that of other vertebrates, we found that ancestral expression patterns were often preserved in higher vertebrates. Morpholino mediated loss of Cldn3b demonstrated a functional role for this protein in placode and pharyngeal arch morphogenesis. Taken together, our data provide novel insights into the origins and evolution of the claudin gene family and the significance of claudin proteins in the evolution of vertebrates. PMID- 27002806 TI - Expressional characterization of mRNA (guanine-7) methyltransferase (rnmt) during early development of Xenopus laevis. AB - Methylation of the guanosine cap structure at the 5' end of mRNA is essential for efficient translation of all eukaryotic cellular mRNAs, gene expression and cell viability and promotes transcription, splicing, polyadenylation and nuclear export of mRNA. In the current study, we present the spatial expression pattern of the Xenopus laevis rnmt homologue. A high percentage of protein sequence similarity, especially within the methyltransferase domain, as well as an increased expression in the cells of the transcriptionally active stages, suggests a conserved RNA cap methylation function. Spatial expression analysis identified expression domains in the brain, the retina, the lens, the otic vesicles and the branchial arches. PMID- 27002807 TI - Unusual Morphologies of Poly(vinyl alcohol) Thin Films Adsorbed on Poly(dimethylsiloxane) Substrates. AB - Adsorption of poly(vinyl alcohol) (PVOH), 99% and 88% hydrolyzed poly(vinyl acetate), to poly(dimethylsiloxane) (PDMS) substrates was studied. The substrates were prepared by covalently attaching linear PDMS polymers of 2, 9, 17, 49, and 116 kDa onto silicon wafers. As the PDMS molecular weight/thickness increases, the adsorbed PVOH thin films progressively transition from continuous to discontinuous morphologies, including honeycomb and fractal/droplet. The structures are the result of thin film dewetting that occurs upon exposure to air. The PVOH film thickness does not vary significantly on these PDMS substrates, implicating the PDMS thickness as the cause for the morphology differences. The adsorbed PVOH thin films are less stable and have a stronger tendency to dewet on thicker, more liquid-like PDMS layers. When PVOH(99%) and PVOH(88%) thin films are compared, fractal and droplet morphologies are observed on high molecular weight PDMS substrates, respectively. The formation of the unique fractal features in the PVOH(99%) thin films as well as other crystalline and semicrystalline thin films is most likely driven by crystallization during the dehydration process in a diffusion-limited aggregation fashion. The only significant enhancement in hydrophilicity via PVOH adsorption was obtained on PDMS(2k), which is completely covered with a PVOH thin film. To mimic the lower receding contact angle and less liquid-like character of the PDMS(2k) substrate, light plasma treatment of the higher molecular weight PDMS substrates was carried out. On the treated PDMS substrates, the adsorbed PVOH thin films are in the more continuous honeycomb morphology, giving rise to significantly enhanced wettability. Furthermore, hydrophobic recovery of the hydrophilized PDMS substrates was not observed during a 1 week period. Thus, light plasma oxidation and subsequent PVOH adsorption can be utilized as a means to effectively hydrophilize conventional PDMS substrates. This study illustrates that the stability and morphology of adsorbed polymer thin films depend on polymer crystallinity as well as substrate physical properties. PMID- 27002809 TI - Ascorbic acid intake and oxalate synthesis. AB - In humans, approximately 60 mg of ascorbic acid (AA) breaks down in the body each day and has to be replaced by a dietary intake of 70 mg in women and 90 mg in men to maintain optimal health and AA homeostasis. The breakdown of AA is non enzymatic and results in oxalate formation. The exact amount of oxalate formed has been difficult to ascertain primarily due to the limited availability of healthy human tissue for such research and the difficulty in measuring AA and its breakdown products. The breakdown of 60 mg of AA to oxalate could potentially result in the formation of up to 30 mg oxalate per day. This exceeds our estimates of the endogenous production of 10-25 mg oxalate per day, indicating that degradative pathways that do not form oxalate exist. In this review, we examine what is known about the pathways of AA metabolism and how oxalate forms. We further identify how gaps in our knowledge may be filled to more precisely determine the contribution of AA breakdown to oxalate production in humans. The use of stable isotopes of AA to directly assess the conversion of vitamin to oxalate should help fill this void. PMID- 27002810 TI - Updated survey of Fusarium species and toxins in Finnish cereal grains. AB - The aim of the project was to produce updated information during 2005-14 on the Fusarium species found in Finnish cereal grains, and the toxins produced by them, as the last comprehensive survey study of Fusarium species and their toxins in Finland was carried out at the turn of the 1960s and the 1970s. Another aim was to use the latest molecular and chemical methods to investigate the occurrence and correlation of Fusarium species and their mycotoxins in Finland. The most common Fusarium species found in Finland in the FinMyco project 2005 and 2006 were F. avenaceum, F. culmorum, F. graminearum, F. poae, F. sporotrichioides and F. langsethiae. F. avenaceum was the most dominant species in barley, spring wheat and oat samples. The occurrence of F. culmorum and F. graminearum was high in oats and barley. Infection by Fusarium fungi was the lowest in winter cereal grains. The incidence of Fusarium species in 2005 was much higher than in 2006 due to weather conditions. F. langsethiae has become much more common in Finland since 2001. F. graminearum has also risen in the order of importance. A highly significant correlation was found between Fusarium graminearum DNA and deoxynivalenol (DON) levels in Finnish oats, barley and wheat. When comparing the FinMyco data in 2005-06 with the results of the Finnish safety monitoring programme for 2005-14, spring cereals were noted as being more susceptible to infection by Fusarium fungi and the formation of toxins. The contents of T-2 and HT-2 toxins and the frequency of exceptionally high DON concentrations all increased in Finland during 2005-14. Beauvericin (BEA), enniatins (ENNs) and moniliformin (MON) were also very common contaminants of Finnish grains in 2005 06. Climate change is leading to warmer weather, and this may indicate more changes in Finnish Fusarium mycobiota and toxin contents and profiles in the near future. PMID- 27002811 TI - Food wastes as fish feeds for polyculture of low-trophic-level fish: bioaccumulation and health risk assessments of heavy metals in the cultured fish. AB - The major purpose of this study was to use different types of food wastes which serve as the major sources of protein to replace the fish meal used in fish feeds to produce quality fish. Two types of food waste-based feed pellets FW A (with cereals) and FW B (with cereals and meat products) and the commercial feed Jinfeng(r) were used to culture fingerlings of three low-trophic-level fish species: bighead carp, grass carp, and mud carp (in the ratio of 1:3:1) for 1 year period in the Sha Tau Kok Organic Farm in Hong Kong. Heavy metal concentrations in all of the fish species fed with food waste pellets and commercial pellets in Sha Tau Kok fish ponds were all below the local and international maximum permissible levels in food. Health risk assessments indicated that human consumption of the fish fed with food waste feed pellets was safe for the Hong Kong residents. The present results revealed that recycling of food waste for cultivating low-trophic-level fish (mainly herbivores and detritus feeders) is feasible, and at the same time will ease the disposal pressure of food waste, a common problem of densely populated cities like Hong Kong. PMID- 27002813 TI - 2016 Annual Meeting Official Proceedings, Volume XVII. PMID- 27002814 TI - Is there a Benefit of Multidisciplinary Cancer Team Meetings for Patients with Gastrointestinal Malignancies? AB - BACKGROUND: Multidisciplinary cancer team meetings are intended to optimize the diagnosis of a patient with a malignancy. The aim of this study was to assess the number of correct diagnoses formulated by the multidisciplinary team (MDT) and whether MDT decisions were implemented. METHODS: In a prospective study, data of consecutive patients discussed at gastrointestinal oncology MDT meetings were studied, and MDT diagnoses were validated with pathology or follow-up. Factors of influence on the correct diagnosis were identified by use of a Poisson regression model. Electronic patient records were used to assess whether MDT decisions were implemented, and reasons to deviate from these decisions were hand-searched within these records. RESULTS: In 74 MDT meetings, 551 patients were discussed a total of 691 times. The MDTs formulated a correct diagnosis for 515/551 patients (93.4 %), and for 120/551 (21.8 %) patients the MDT changed the referral diagnosis. Of the MDT diagnoses, 451/515 (87.6 %) were validated with pathology. Patients presented to the MDT by their treating physician were 20 % more likely to receive a correct diagnosis [relative risk (RR) 1.2, 95 % confidence interval (CI) 1.1-1.5], while the number of patients discussed or the duration of the meeting had no influence on this (RR 1.0, 95 % CI 0.99-1.0; RR 1.0, 95 % CI 0.9 1.1; resp.). MDT decisions were implemented in 94.4 % of cases. Deviations of MDT decisions occurred when a patient's wishes or physical condition were not taken into account. CONCLUSIONS: MDTs rectify 20 % of the referral diagnoses. The presence of the treating physician is the most important factor to ensure a correct diagnosis and adherence to the treatment plan. PMID- 27002815 TI - Botulinum toxin therapy: reduction of injection site pain by pH normalisation. AB - Botulinum toxin (BT) is injected intramuscularily and may produce injection site pain (ISP). We wanted to explore whether the pH value of the reconstituted BT drug contributes to ISP and, if so, what strategies can be applied to reduce it. In part 1 of the study, pH values of different reconstitution solutions and of major BT drugs reconstituted with different reconstitution solutions were assessed. In part 2, the effects of reconstitution with normal saline (NS) and Ringer acetate (RA) were compared intraindividually and in a double blind fashion in 34 patients with blepharospasm. pH values of reconstitution solutions were 5.52 +/- 0.02 for NS, 6.98 for RA, 6.31 for Ringer lactate, 6.56 for electrolyte and 5.31 for bacteriostatic solution. pH values for NS-reconstitution were 6.09 +/- 0.20 for Botox((r)), 5.95 +/- 0.24 for Dysport((r)) and 5.81 +/- 0.18 for Xeomin((r)). pH values for RA-reconstitution were 6.95 +/- 0.03 for Botox((r)), 7.01 +/- 0.02 for Dysport((r)) and 6.87 +/- 0.06 for Xeomin((r)). By using RA instead of NS the pH could be increased by 0.86 for Botox((r)), by 1.06 for Dysport((r)) and by 1.06 for Xeomin((r)). 47 % of the patients experienced less ISP when Botox((r))-RA was given rather than Botox((r))-NS, 76 % when Xeomin((r)) RA was given rather than Xeomin((r))-NS. None of the patients reported a difference in efficacy between NS- and RA-reconstitution. Despite previous reports, reconstituted BT type A drugs show acidic pH values. Normalising these pH values by use of RA instead of NS reduces ISP considerably without sacrificing clincial efficacy. PMID- 27002812 TI - Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group. AB - Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders. PMID- 27002816 TI - Adverse Childhood Experiences Among Inpatient Youths with Severe and Early-Onset Psychiatric Disorders: Prevalence and Clinical Correlates. AB - This study aimed to determine the prevalence and the clinical correlates of Adverse Childhood Experiences (ACEs) among 158 inpatient youths with two types of severe psychiatric disorders. ACEs were retrospectively collected with the ACEs scale and the List of Threatening Experiences Questionnaire in 77 patients hospitalized for a catatonic syndrome (average age 15.2 years) and 81 for a manic or mixed episode (average age 15.7 years). ACEs were frequent in youths suffering from bipolar disorder type I (BD-I) (58 %) and from catatonia (57 %), with around one quarter exposed to severe abuse (i.e., physical/sexual/emotional abuse or physical/emotional neglect). Youths with BD-I were more likely to be exposed to family violence compared to those with catatonia. Youths who had been exposed to ACEs did not exhibit a more severe presentation or a poorer response to treatment compared to others, either in the bipolar group or in the catatonic group. PMID- 27002817 TI - The impact of hypoxia on intestinal epithelial cell functions: consequences for invasion by bacterial pathogens. AB - The maintenance of oxygen homeostasis in human tissues is mediated by several cellular adaptations in response to low-oxygen stress, called hypoxia. A decrease in tissue oxygen levels is initially counteracted by increasing local blood flow to overcome diminished oxygenation and avoid hypoxic stress. However, studies have shown that the physiological oxygen concentrations in several tissues are much lower than atmospheric (normoxic) conditions, and the oxygen supply is finely regulated in individual cell types. The gastrointestinal tract has been described to subsist in a state of physiologically low oxygen level and is thus depicted as a tissue in the state of constant low-grade inflammation. The intestinal epithelial cell layer plays a vital role in the immune response to inflammation and infections that occur within the intestinal tissue and is involved in many of the adaptation responses to hypoxic stress. This is especially relevant in the context of inflammatory disorders, such as inflammatory bowel disease (IBD). Therefore, this review aims to describe the intestinal epithelial cellular response to hypoxia and the consequences for host interactions with invading gastrointestinal bacterial pathogens. PMID- 27002818 TI - Design and Development of a Sharable Clinical Decision Support System Based on a Semantic Web Service Framework. AB - Clinical decision support (CDS) systems provide clinicians and other health care stakeholders with patient-specific assessments or recommendations to aid in the clinical decision-making process. Despite their demonstrated potential for improving health care quality, the widespread availability of CDS systems has been limited mainly by the difficulty and cost of sharing CDS knowledge among heterogeneous healthcare information systems. The purpose of this study was to design and develop a sharable clinical decision support (S-CDS) system that meets this challenge. The fundamental knowledge base consists of independent and reusable knowledge modules (KMs) to meet core CDS needs, wherein each KM is semantically well defined based on the standard information model, terminologies, and representation formalisms. A semantic web service framework was developed to identify, access, and leverage these KMs across diverse CDS applications and care settings. The S-CDS system has been validated in two distinct client CDS applications. Model-level evaluation results confirmed coherent knowledge representation. Application-level evaluation results reached an overall accuracy of 98.66 % and a completeness of 96.98 %. The evaluation results demonstrated the technical feasibility and application prospect of our approach. Compared with other CDS engineering efforts, our approach facilitates system development and implementation and improves system maintainability, scalability and efficiency, which contribute to the widespread adoption of effective CDS within the healthcare domain. PMID- 27002819 TI - Intracortical inhibition in the soleus muscle is reduced during the control of upright standing in both young and old adults. AB - PURPOSE: In a previous study, we reported that a short-interval intracortical inhibition (SICI) decreases in old but not in young adults when standing on foam vs. a rigid surface. Here, we examined if such an age by task difficulty interaction in motor cortical excitability also occurs in easier standing tasks. METHODS: Fourteen young (23 +/- 2.7 years) and fourteen old (65 +/- 4.1 years) adults received transcranial magnetic brain stimulation and peripheral nerve stimulation, while they stood with or without support on a force platform. RESULTS: In the soleus, we found that SICI was lower in unsupported (35 % inhibition) vs. supported (50 %) standing (p = 0.007) but similar in young vs. old adults (p = 0.591). In the tibialis anterior, SICI was similar between conditions (p = 0.597) but lower in old (52 %) vs. young (72 %) adults (p = 0.030). Age and standing with or without support did not affect the Hoffmann reflex in the soleus. CONCLUSIONS: The current data suggest that the motor cortex is involved in standing control, and that its role becomes more prominent with an increase in task difficulty. PMID- 27002820 TI - Topical application of cream containing nonivamide and nicoboxil does not enhance the performance of experienced cyclists during a 4-km time-trial. AB - PURPOSE: Topical application of nonivamide-nicoboxil cream to resting legs has been shown to enhance the level of oxygenated haemoglobin in leg muscles 15 min later. Here, we examined whether such application improves the performance of experienced cyclists in a subsequent 4-km time-trial. METHODS: Nine male cyclists [26 +/- 8 years; 176 +/- 9 cm; 73.5 +/- 12.8 kg; peak oxygen uptake: 50.7 +/- 4.0 mL min(-1) kg(-1) (mean +/- SD)] performed three 4-km time-trials on an ergometer with either topical application of nonivamide-nicoboxil cream (CREAM) or cream without active components (SHAM) to both their thigh muscles or no application (CONTROL). RESULTS: Only the skin temperature immediately before and after the time-trial was higher with cream than SHAM and CONTROL (best p < 0.001, best d = 1.16). All other parameters evaluated, i.e., the average power output during the time-trial (p > 0.05, best d = 0.08), the tissue saturation index of the m. vastus lateralis (p > 0.05, best d = 0.57), cardiac output, heart rate, oxygen uptake, blood lactate concentration, and perceived exertion (p > 0.05, best d = 1.1) were similar under all three conditions. CONCLUSIONS: Our present findings reveal that topical application of cream containing nonivamide and nicoboxil to the thighs of cyclists prior to a 4-km time-trial does not improve their power output, saturation of the m. vastus lateralis with oxygen, oxygen uptake, heart rate, cardiac parameters, or perceived level of exertion. PMID- 27002821 TI - Vasculoprotective Effects of 3-Hydroxybenzaldehyde against VSMCs Proliferation and ECs Inflammation. AB - 3-hydroxybenzaldehyde (3-HBA) is a precursor compound for phenolic compounds like Protocatechuic aldehyde (PCA). From recent reports, PCA has shown vasculoprotective potency, but the effects of 3-HBA remain unclear. The aim of this study is to investigate the vasculoprotective effects of 3-HBA in endothelial cells, vascular smooth muscle cells and various animal models. We tested effects of 3-HBA in both vitro and vivo. 3-HBA showed that it prevents PDGF-induced vascular smooth muscle cells (VSMCs) migration and proliferation from MTS, BrdU assays and inhibition of AKT phosphorylation. It arrested S and G0/G1 phase of VSMC cell cycle in PI staining and it also showed inhibited expression levels of Rb1 and CD1. In human umbilical vein endothelial cells (HUVECs), 3-HBA inhibited inflammatory markers and signaling molecules (VCAM-1, ICAM-1, p-NF-kappaB and p-p38). For ex vivo, 3-HBA has shown dramatic effects in suppressing the sprouting from aortic ring of Spargue Dawley (SD) rats. In vivo data supported the vasculoprotective effects of 3-HBA as it inhibited angiogenesis from Matrigel Plug assay in C57BL6 mouse, prevented ADP-induced thrombus generation, increased blood circulation after formation of thrombus, and attenuated neointima formation induced by common carotid artery balloon injury of SD rats. 3-HBA, a novel therapeutic agent, has shown vasculoprotective potency in both in vitro and in vivo. PMID- 27002822 TI - Tree Biomass Allocation and Its Model Additivity for Casuarina equisetifolia in a Tropical Forest of Hainan Island, China. AB - Casuarina equisetifolia is commonly planted and used in the construction of coastal shelterbelt protection in Hainan Island. Thus, it is critical to accurately estimate the tree biomass of Casuarina equisetifolia L. for forest managers to evaluate the biomass stock in Hainan. The data for this work consisted of 72 trees, which were divided into three age groups: young forest, middle-aged forest, and mature forest. The proportion of biomass from the trunk significantly increased with age (P<0.05). However, the biomass of the branch and leaf decreased, and the biomass of the root did not change. To test whether the crown radius (CR) can improve biomass estimates of C. equisetifolia, we introduced CR into the biomass models. Here, six models were used to estimate the biomass of each component, including the trunk, the branch, the leaf, and the root. In each group, we selected one model among these six models for each component. The results showed that including the CR greatly improved the model performance and reduced the error, especially for the young and mature forests. In addition, to ensure biomass additivity, the selected equation for each component was fitted as a system of equations using seemingly unrelated regression (SUR). The SUR method not only gave efficient and accurate estimates but also achieved the logical additivity. The results in this study provide a robust estimation of tree biomass components and total biomass over three groups of C. equisetifolia. PMID- 27002823 TI - Psychometric Properties of the Japanese Version of the STarT Back Tool in Patients with Low Back Pain. AB - BACKGROUND AND OBJECTIVE: The STarT Back Tool uses prognostic indicators to classify patients with low back pain into three risk groups to guide early secondary prevention in primary care. The present study aimed to evaluate the psychometric properties of the Japanese version of the tool (STarT-J). METHODS: An online survey was conducted among Japanese patients with low back pain aged 20 64 years. Reliability was assessed by examining the internal consistency of the overall and psychosocial subscales using Cronbach's alpha coefficients. Spearman's correlation coefficients were used to evaluate the concurrent validity between the STarT-J total score/psychosocial subscore and standard reference questionnaires. Discriminant validity was evaluated by calculating the area under the curves (AUCs) for the total and psychosocial subscale scores against standard reference cases. Known-groups validity was assessed by examining the relationship between low back pain-related disability and STarT-J scores. RESULTS: The analysis included data for 2000 Japanese patients with low back pain; the mean (standard deviation [SD]) age was 47.7 (9.3) years, and 54.1% were male. The mean (SD) STarT-J score was 2.2 (2.1). The Cronbach's alpha coefficient was 0.75 for the overall scale and 0.66 for the psychosocial subscale. Spearman's correlation coefficients ranged from 0.30 to 0.59, demonstrating moderate to strong concurrent validity. The AUCs for the total score ranged from 0.65 to 0.83, mostly demonstrating acceptable discriminative ability. For known-groups validity, participants with more somatic symptoms had higher total scores. Those in higher STarT-J risk groups had experienced more low back pain-related absences. CONCLUSIONS: The overall STarT-J scale was internally consistent and had acceptable concurrent, discriminant, and known-groups validity. The STarT-J can be used with Japanese patients with low back pain. PMID- 27002824 TI - The Distribution and Host Shifts of Cotton-Melon Aphids in Northern China. AB - Aphis gossypii Glover (Hemiptera: Aphididae) is a serious pest of cotton in northern China. A microsatellite analysis was used to characterize the genetic structure of A. gossypii populations from different geographic, host plant, and seasonal populations in 2014. Among 906 individuals, 507 multilocus genotypes were identified, with genotypic richness values of 0.07-1.00 for the populations. We observed moderate levels of genetic differentiation among geographic populations (FST = 0.103; 95% confidence interval: 0.065-0.145) and host plant populations (FST = 0.237; 95% confidence interval: 0.187-0.296). A Mantel test of isolation by distance revealed no significant correlations between Slatkin's linearized FST and the natural logarithm of geographic distance. A Bayesian analysis of population genetic structures identified three clusters. An analysis of molecular variance revealed significant differences among the three clusters (F = 0.26596, P < 0.0001), among seasons (F = 0.04244, P = 0.00381), and among host populations (F = 0.12975, P = 0.0029). Thus, the A. gossypii populations in northern China exhibit considerable genotypic diversity. Additionally, our findings indicated that the 31 analyzed populations could be classified as one of three host biotypes (i.e., cotton, cucumber, and pomegranate biotypes). There were also clear seasonal effects on population genetic structure diversity among aphids collected from Anyang. PMID- 27002825 TI - Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide. AB - OBJECTIVE: To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). METHODS: We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria <=0.33g/day and serum creatinine <=124 umol/l. Partial remission (PR) was defined as proteinuria <=1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. RESULTS: Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 +/- 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile->105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile->105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. CONCLUSION: This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients. PMID- 27002826 TI - Vestibular function disorders and potential mechanisms in irradiation nasopharyngeal carcinoma patients. AB - CONCLUSIONS: Vestibular function disorders were widespread among nasopharyngeal carcinoma (NPC) patients. The radiation doses to the inner ears were associated with the incidence of vestibular function disorders, but the correlations were mild. The inflammatory responses and possible resolution obstacles of inflammation participated in persistent vestibular function disorders after irradiation. OBJECTIVES: To investigate the incidence of vestibular function disorders in NPC patients after irradiation and potential mechanisms. METHODS: Patients who received radical intensity-modulated radiotherapy for their NPC were recruited. The serum levels of IL-6 and IL-17 were detected by ELISA method. Vestibular evoked myogenic potential (VEMP) tests were used to evaluate vestibular function and correlation analyses were used to analyze the potential mechanisms of vestibular function disorders. RESULTS: Thirty-eight patients were included. The incidences of abnormal ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were 65.79% and 80.26% at the time of completion of radiotherapy, and 61.84% and 71.05% at 3 months after radiotherapy. The mean and maximum radiation doses to the inner ears were both significantly associated with abnormal oVEMP and cVEMP (p < 0.05, all), but the correlations were all mild. The serum levels of IL-6 and IL-17 were both significantly associated with abnormal oVEMP and cVEMP after irradiation (p < 0.05, all). PMID- 27002828 TI - Investigation of early and advanced stages in ovarian cancer using human plasma by differential scanning calorimetry and mass spectrometry. AB - Ovarian cancer is recognized with high mortality due to asymptomatic nature of the disease and difficulties in diagnosing early stage of the cancer. The present study evaluates the use of differential scanning calorimetry (DSC) in differentiating the severity of ovarian cancer from healthy women. 47 diseased women were subdivided into four stages with respect to clinical relevance and severity. Stages I-II were regarded as early stages and stages III-IV were regarded as advanced stages. The two average transition temperatures (T m ) increased with disease severity from 64.84 and 70.32 degrees C (healthy) to 68.46 and 75.24 degrees C (stage IV), respectively. T m were increased depending on clinical groups. In addition, the change in heat capacity was also dependent on the disease severity. To further support and investigate the nature of the proposed interactions, matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis is employed. The results suggest the differences in peptide expression between early and advanced stage of ovarian cancer, affected abundant proteins in plasma. The combined DSC and MS approach was supportive in identifying a unique signature of ovarian cancer stages, and demonstrates the potential of DSC as a complementary diagnostic tool in the evaluation of early stage ovarian cancer. PMID- 27002827 TI - Hypothalamic Phosphodiesterase 3B Pathway Mediates Anorectic and Body Weight Reducing Effects of Insulin in Male Mice. AB - BACKGROUND: Insulin action in the hypothalamus plays a critical role in the regulation of energy homeostasis, yet the intracellular signaling mechanisms mediating insulin action are incompletely understood. Although phosphodiesterase 3B (PDE3B) mediates insulin action in the adipose tissue and it is highly expressed in the hypothalamic areas implicated in energy homeostasis, its role, if any, in mediating insulin action in the hypothalamus is unknown. We tested the hypothesis that insulin action in the hypothalamus is mediated by PDE3B. METHODS: Using enzymatic assay, we examined the effects of peripheral or central administration of insulin on hypothalamic PDE3B activity in adult mice. Western blotting and immunohistochemistry also examined p-Akt and p-STAT3 levels in the hypothalamus. Effects of leptin on these parameters were also compared. We injected cilostamide, a PDE3 inhibitor, prior to central injection of insulin and examined the 12- to 24-hour food intake and 24-hour body weight. Finally, we examined the effect of cilostamide on insulin-induced proopiomelanocortin (Pomc), neurotensin (Nt), neuropeptide Y (Npy) and agouti-related peptide (Agrp) gene expression in the hypothalamus by qPCR. RESULTS: Peripheral or central injection of insulin significantly increased PDE3B activity in the hypothalamus in association with increased p-Akt levels but without any change in p-STAT3 levels. However, leptin-induced increase in PDE3B activity was associated with an increase in both p-Akt and p-STAT3 levels in the hypothalamus. Prior administration of cilostamide reversed the anorectic and body weight-reducing effects as well as stimulatory effect of insulin on hypothalamic Pomc mRNA levels. Insulin did not alter Nt, Npy and Agrp mRNA levels. CONCLUSION: Insulin induction of hypothalamic PDE3B activity and the reversal of the anorectic and body weight-reducing effects and stimulatory effect of insulin on hypothalamic Pomc gene expression by cilostamide suggest that activation of PDE3B is a novel mechanism of insulin signaling in the hypothalamus. PMID- 27002829 TI - Sonography of Normal and Abnormal Thyroid and Parathyroid Glands. AB - Ultrasonography (US) represents the most sensitive and efficient method for the evaluation of the thyroid and parathyroid glands. Infectious and autoimmune thyroiditis are common diseases, usually diagnosed and followed up by clinical examination and laboratory analyses. Nevertheless, US plays an important role in confirming diagnoses, predicting outcomes and, in autoimmune hyperthyroidism, in titrating therapy. Conversely, in nodular thyroid disease US is the imaging method of choice for the characterization and surveillance of lesions. It provides consistent clues in predicting the risk of malignancy, thus directing patient referral for fine-needle aspiration (FNA) biopsy. Suspicious US features generally include marked hypoechogenicity, a shape taller than it is wide, ill defined or irregular borders, microcalcifications and hardness at elastographic evaluation. Finally, the role of US in thyroid cancer is to evaluate extension beyond the thyroid capsule and to assess nodal metastases or tumor recurrence. The main application of US in parathyroid diseases is represented by primary hyperparathyroidism. In this condition, US plays a role after biochemical diagnosis, and it should always be strictly performed for localization purposes. In both thyroidal and parathyroid diseases, US is recommended as a guide in FNA biopsies. PMID- 27002830 TI - Regulating a Post-Transcriptional Regulator: Protein Phosphorylation, Degradation and Translational Blockage in Control of the Trypanosome Stress-Response RNA Binding Protein ZC3H11. AB - The life cycle of the mammalian pathogen Trypanosoma brucei involves commuting between two markedly different environments: the homeothermic mammalian host and the poikilothermic invertebrate vector. The ability to resist temperature and other stresses is essential for trypanosome survival. Trypanosome gene expression is mainly post-transcriptional, but must nevertheless be adjusted in response to environmental cues, including host-specific physical and chemical stresses. We investigate here the control of ZC3H11, a CCCH zinc finger protein which stabilizes stress response mRNAs. ZC3H11 protein levels increase at least 10-fold when trypanosomes are stressed by heat shock, proteasome inhibitors, ethanol, arsenite, and low doses of puromycin, but not by various other stresses. We found that increases in protein stability and translation efficiency both contribute to ZC3H11 accumulation. ZC3H11 is an in vitro substrate for casein kinase 1 isoform 2 (CK1.2), and results from CK1.2 depletion and other experiments suggest that phosphorylation of ZC3H11 can promote its instability in vivo. Results from sucrose density centrifugation indicate that under normal culture conditions translation initiation on the ZC3H11 mRNA is repressed, but after suitable stresses the ZC3H11 mRNA moves to heavy polysomes. The ZC3H11 3'-UTR is sufficient for translation suppression and a region of 71 nucleotides is required for the regulation. Since the control works in both bloodstream forms, where ZC3H11 translation is repressed at 37 degrees C, and in procyclic forms, where ZC3H11 translation is activated at 37 degrees C, we predict that this regulatory RNA sequence is targeted by repressive trans acting factor that is released upon stress. PMID- 27002831 TI - Subverting misconceptions about radiation therapy. PMID- 27002832 TI - Reply to: "Subverting misconceptions about radiation therapy". PMID- 27002833 TI - ReGLUation of cGAS. PMID- 27002834 TI - Barrier regulation: tolerance stops at cell death. PMID- 27002835 TI - Transcriptionally defining ILC heterogeneity in humans. PMID- 27002836 TI - Big impact of microRNAs on central B cell tolerance. PMID- 27002845 TI - Erratum: Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity. PMID- 27002844 TI - Emerging concepts of T cell metabolism as a target of immunotherapy. AB - T cells have a pivotal protective role in defense against infection and cancer but also are instrumental in the development of many autoimmune diseases. The regulation of nutrient uptake and utilization in T cells is critically important for the control of their differentiation, and manipulating metabolic pathways in these cells can alter their function and longevity. While the importance of T cell metabolic remodeling in different physiological settings is not fully understood, there is a growing realization that inappropriate metabolic remodeling underlies many aberrant immune responses and that manipulating cellular metabolism can beneficially enhance or temper immunity. Here we comment on the basic metabolic pathways in T cells, followed by a discussion on up-to date findings about the relationship between metabolism and T cell function and longevity. Furthermore, we expand on potential approaches and applications in which T cells might be manipulated by the reprogramming of metabolic pathways for therapeutic purposes. PMID- 27002843 TI - Innate cell communication kick-starts pathogen-specific immunity. AB - Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, including innate cells and epithelial cells. Rather than acting as isolated effector cells, innate cells are in constant communication with other responding cells of the immune system, locally and distally. These interactions are critically important for the efficient control of primary infections as well for the development of 'trained' innate cells that facilitate the rapid elimination of homologous or heterologous infections. PMID- 27002846 TI - Corrigendum: The burgeoning family of unconventional T cells. PMID- 27002848 TI - Erratum: Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment. PMID- 27002849 TI - Corrigendum: Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events. PMID- 27002850 TI - Medical management of glaucoma: focus on ophthalmologic drug delivery systems of timolol maleate. AB - Eye is a vital organ of our body and any complication not only poses the risk of serious medical condition but also economic burden on the individual. Timolol maleate is one of the preferable therapeutic agents for the management of glaucoma. Globally, eye drops are among the most common and popular conventional formulations, but they are also associated with some limitations in terms of therapeutic response, bioavailability, dosing frequency and poor patient compliance. Present paper gives an overview of the drug delivery systems developed for management of glaucoma, advances and novel approaches with special emphasis on timolol drug delivery. PMID- 27002851 TI - TLR4-Dependent Secretion by Hepatic Stellate Cells of the Neutrophil Chemoattractant CXCL1 Mediates Liver Response to Gut Microbiota. AB - BACKGROUND & AIMS: The gut microbiota significantly influences hepatic immunity. Little is known on the precise mechanism by which liver cells mediate recognition of gut microbes at steady state. Here we tested the hypothesis that a specific liver cell population was the sensor and we aimed at deciphering the mechanism by which the activation of TLR4 pathway would mediate liver response to gut microbiota. METHODS: Using microarrays, we compared total liver gene expression in WT versus TLR4 deficient mice. We performed in situ localization of the major candidate protein, CXCL1. With an innovative technique based on cell sorting, we harvested enriched fractions of KCs, LSECs and HSCs from the same liver. The cytokine secretion profile was quantified in response to low levels of LPS (1ng/mL). Chemotactic activity of stellate cell-derived CXCL1 was assayed in vitro on neutrophils upon TLR4 activation. RESULTS: TLR4 deficient liver had reduced levels of one unique chemokine, CXCL1 and subsequent decreased of neutrophil counts. Depletion of gut microbiota mimicked TLR4 deficient phenotype, i.e., decreased neutrophils counts in the liver. All liver cells were responsive to low levels of LPS, but hepatic stellate cells were the major source of chemotactic levels of CXCL1. Neutrophil migration towards secretory hepatic stellate cells required the TLR4 dependent secretion of CXCL1. CONCLUSIONS: Showing the specific activation of TLR4 and the secretion of one major functional chemokine-CXCL1, the homolog of human IL-8-, we elucidate a new mechanism in which Hepatic Stellate Cells play a central role in the recognition of gut microbes by the liver at steady state. PMID- 27002852 TI - Socioeconomic Disconnection as a Risk Factor for Increased HIV Infection in Young Men Who Have Sex with Men. AB - PURPOSE: HIV disproportionately affects young men who have sex with men (YMSM), particularly black YMSM. Increasingly, researchers are turning to social, economic, and structural factors to explain these disproportionate rates. In this study, we explore the relationship between socioeconomic disconnection and HIV status and factors related to HIV infection, including drug use, condomless anal sex, and binge drinking. We operationalize socioeconomic disconnection in this young population as lack of engagement in educational and employment opportunities. METHODS: Baseline data were analyzed from a longitudinal cohort study of YMSM aged 16-20 years recruited from the Chicago area (N = 450). Bivariate analyses of the association of socioeconomic disconnection and HIV positive status, drug and alcohol use, and condomless anal sex were assessed using chi-square tests. The relationship of socioeconomic disconnection and HIV positive status was then examined in multivariate logistic regression models, controlling for age and race/ethnicity and significant behavioral factors. RESULTS: Among study participants, 112 (25%) were not in school, 310 (69%) were not currently working, and 81 (18%) were neither in school nor working. Black MSM were more likely to be socioeconomically disconnected (neither in school nor working; n = 56, 23.3%). The results revealed that disconnected YMSM were more likely to binge drink (AOR = 2.34; 95% CI = 1.16, 4.74) and be HIV positive (AOR = 2.24; 95% CI = 1.04, 4.83). Subpopulation analysis for black participants revealed similar associations (AOR of binge drinking = 2.92; 95% CI = 1.07, 8.01; AOR of HIV positive = 2.38; 95% CI = 1.03, 5.51). Controlling for substance use, the association between disconnection and HIV-positive status remained significant (AOR = 2.37; 95% CI = 1.08, 5.20). CONCLUSION: Socioeconomic disconnection is significantly and positively associated with HIV status among YMSM, suggesting that the two factors are related. Socioeconomic factors present an important area for future research focusing on HIV infection in this high-risk group. PMID- 27002853 TI - Risk factors for KPC-producing Klebsiella pneumoniae: watch out for surgery. AB - This study describes the molecular characteristics and risk factors associated with carbapenem-resistant Klebsiella pneumoniae strains. Risk factors associated with KPC-producing K. pneumoniae strains were investigated in this case-control study from May 2011 to May 2013. Bacterial identification was performed by matrix assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined by broth microdilution. Carbapenemase production was assessed by both modified Hodge test (MHT) and ertapenem hydrolysis using MALDI-TOF MS. The presence of beta-lactamase-encoding genes was evaluated by PCR and DNA sequencing. Alterations in genes encoding K. pneumoniae outer membrane proteins were analysed by PCR and DNA sequencing as well as SDS-PAGE. Genetic relatedness among strains was determined by pulsed field gel electrophoresis. This study included 94 patients. Longer hospitalisation, mechanical ventilation, catheters, and previous surgery were associated with KPC-producing K. pneumoniae. Sixty-eight strains showed resistance to carbapenems. Carbapenemase production was detected by MHT in 67 K. pneumoniae strains and by MALDI-TOF MS in 57. The presence of the blaKPC-2 gene was identified in 57 strains. The blaKPC-2 gene was not found in 11 carbapenem resistant K. pneumoniae; instead, the blaCTX-M-1-like, blaCTX-M-2-like, blaCTX-M 8 like, blaCTX-M-14-like and blaSHV- like genes associated with OmpK35 and OmpK36 alterations were observed. Thirty-three KPC-producing K. pneumoniae strains were clonally related, and patients infected with these strains had a higher mortality rate (78.78 %). Our results show that KPC-producing K. pneumoniae was associated with several healthcare-related risk factors, including recent surgery. PMID- 27002854 TI - Therapy Modalities for Antibody Mediated Rejection in Renal Transplant Patients. AB - INTRODUCTION: The aim of our study was to determine the effectiveness of immunoglobulin, rituximab and plasmapheresis in renal transplant patients with antibody mediated rejection (AMR). PATIENTS AND METHODS: Fourteen renal transplant patients with AMR were included in this study. The mean age of the patients was 33.9 +/- 10.3 years and 10 (71.4%) of them were male. Lymphocyte cross match was negative for all patients and 10 (71.4%) of them were living donor transplants. Six patients were administered tacrolimus, three patients cyclosporine, two patients everolimus, and three patients sirolimus for immunosuppression. The patients with AMR were administered IVIG, rituximab and plasmapheresis. RESULTS: Patient survival rate was 100%, graft survival rate after AMR was 50% in the first year and 33% in the 2nd and third years. AMR developed 31.9 +/- 25.9 months after transplantation. Seven (50%) patients lost their grafts. Delayed graft function was observed in 28.6%, chronic allograft dysfunction in 78.5%, diabetes after transplantation in 14.3%, and cytomegalovirus infection in 7.1% of the patients. At the last follow-up, the mean blood creatinine was 3.1 +/- 1.4, the mean proteinuria was 2300 (1300-3300) mg/day and the mean GFR was 34.5 +/- 17.6 ml/min. C4d was positive in peritubullar capillaries in all patients, while neutrophil accumulation in peritubular and glomerular capillaries was observed in 8 patients. Chronic allograft vasculopathy was observed in 12 patients. CONCLUSION: AMR leads to progressive loss of renal function and has low graft survival. More effective treatment alternatives are needed for this clinical issue. PMID- 27002855 TI - The Economic Burden of Autonomic Dysreflexia during Hospitalization for Individuals with Spinal Cord Injury. AB - We sought to determine the economic burden of autonomic dysreflexia (AD) from the perspective of the Canadian healthcare system in a case series of individuals with spinal cord injury (SCI) presenting to emergency care. In doing so, we sought to illustrate the potential return on investments in the translation of evidence-informed practices and developments in the prevention, diagnosis, and management of AD. Activity-based costing methodology was employed to estimate the direct healthcare or hospitalization costs of AD following presentation to the emergency department. Differences in trends were noted between patients who were promptly diagnosed, managed, and discharged, and patients whose experience followed a less direct or ideal path to discharge. We recorded 29 emergency room visits for conditions ultimately diagnosed as AD. Overall, median length of stay was 3 days (interquartile range [IQR] = 1.25-5.75), but extended up to 103 consecutive days. Cost analysis revealed median healthcare costs of $5029 (IQR = $2397-9522) for hospital admissions for AD, with the highest estimated hospital cost for a single admission > $190,000. Emergency room admissions resulting from AD can result in dramatic healthcare costs. Delayed diagnosis and inefficient management of AD may lead to further complications, adding to the strain on already limited healthcare resources. Prompt recognition of AD; broader translation of evidence-informed practices; and novel diagnosis, self-management, and/or therapeutic/pharmaceutical applications may prove to mitigate the burden of AD and improve patient well-being. PMID- 27002856 TI - [Evidence/Transparence: ENT - Quo vadis? : 87th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery in Dusseldorf, May 4(th) 7(th), 2016]. PMID- 27002857 TI - [Balloon dilatation of the Eustachian tube during middle ear surgery : Study planning and first experiences during recruitment]. AB - BACKGROUND: Eustachian tube dysfunction is considered a major contributor to chronic middle ear disease. In clinical case series, the results of balloon dilation (balloon Eustachian tuboplasty, BET) as a treatment for Eustachian tube dysfunction have been reported. OBJECTIVE: This study aims to analyze whether patients undergoing planned surgery for chronic middle ear disease would benefit from additional BET. METHODS: In a randomized controlled, patient and observer (not surgeon)-blind clinical study, 100 adult patients with planned surgery for chronic middle ear disease will be investigated. Patients will be randomized into two groups, one of which (50%) will receive additional BET of the affected side during the planned surgery. Eustachian tube function will be evaluated using the Valsalva maneuver and tubomanometry according to Esteve, as well as on the basis of patient reports. Various scores will be used as outcome measures, including ETS-5 (Eustachian Tube Score 5), the extended version ETS-7, and the ETDQ-7 (Seven-Item Eustachian Tube Dysfunction Questionnaire). Follow-up is at 3, 6, and 12 months. RESULTS: From June to December 2015, 162 patients underwent microscopic ear surgery. Inclusion criteria were not fulfilled by 90 patients. Of the remaining 72 patients with chronic middle ear disease, 12 patients (17%) have been randomized so far, 28 (39%) did not exhibit Eustachian tube dysfunction, and 32 (44%) patients could not be included for other reasons. CONCLUSION: The rate of recruitment was lower than expected. Depending on the case number calculations for the patient groups identified in the study for whom BET might be particularly beneficial, multicenter studies in specific disease groups may follow. PMID- 27002858 TI - Comparisons of Cocaine-Only, Opioid-Only, and Users of Both Substances in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). AB - BACKGROUND: Cocaine and opioid co-use is a notable public health concern, but little is known about correlates of this behavior. Most prior findings come from treatment samples and concern cocaine and heroin. Findings from a nationally representative sample involving primarily prescription opioid misuse would expand knowledge. METHODS: Past-12-month cocaine and/or opioid users in Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) formed the sample (N = 839). Cocaine-only, opioid-only, and cocaine/opioid co-users were compared regarding sociodemographics, other substance involvement, psychiatric, and medical conditions/events. RESULTS: Opioid-only users were the largest group (n = 622), followed by cocaine-only (n = 144) and co-users (n = 73). The vast majority of opioid misuse was of prescription opioids (1.4% with past-12-month use of heroin). Notably, co-users did not differ from single drug users in frequency of use of either drug. Co-users did not have significantly greater incidence of any psychiatric conditions, medial conditions, or events. In preliminary analyses, co-users were more likely than either single use group to report several classes of other drug use. However, for most comparisons, opioid use did not add substantial risk beyond cocaine use. Differences on multiple sociodemographic variables suggested opioid-only users were at lowest risk of negative outcomes. These results may relate to a finding that opioid-only users were less likely to have sought treatment. CONCLUSIONS/IMPORTANCE: This sample of past-12-month cocaine and/or opioid users had greater involvement with other substances, more psychiatric and medical conditions compared to the general population. Co-users had greater involvement with other substances than opioid only users in particular. PMID- 27002859 TI - Impact of a workplace intervention on attitudes and practices related to gender equity in Bengaluru, India. AB - We describe the evaluation of a participatory, garment factory-based intervention to promote gender equity. The intervention comprised four campaigns focused on gender and violence against women, alcoholism, sexual and reproductive health, and HIV/AIDS, which were implemented using information displays (standees and posters) and interactive methods (street play, one-to-one interactions, experience-sharing, and health camps). Each campaign lasted six days and the entire intervention was implemented over 10 months. We evaluated the intervention using a quasi-experimental design in which one factory served as the intervention site and a second as a delayed control. Two mobile-phone-based cross-sectional surveys were conducted at baseline and 12 months with separate systematic random samples of employees from each site. Data on socio-demographic characteristics and knowledge and attitudes related to gender equity, intimate partner violence (IPV) and alcohol use were assessed, and differences in these variables associated with the intervention were examined using difference-in-difference estimation. Analyses of data from 835 respondents revealed substantial, statistically significant improvements in attitudes related to gender equity, unacceptability of IPV, and awareness of IPV and alcohol-related support services. In conclusion, our study offers compelling evidence on the effectiveness of workplace-based interventions in advancing gender equity. PMID- 27002860 TI - Improved pharmacokinetics of mercaptopurine afforded by a thermally robust hemihydrate. AB - Structural and thermal data were obtained for a novel hemihydrate of 6 mercaptopurine. The hemihydrate shows increased solubility and bioavailability when compared to the monohydrate form, better stability against conversion in aqueous media than the anhydrate form, and a dehydration temperature of 240 degrees C, the highest of any known hydrate crystal. PMID- 27002862 TI - An efficient and sensitive fluorescent pH sensor based on amino functional metal organic frameworks in aqueous environment. AB - A pH sensor is fabricated via a reaction between an Al(III) salt and 2 aminoterephthalic acid in DMF which leads to a MOF (Al-MIL-101-NH2) with free amino groups. The Al-MIL-101-NH2 samples show good luminescence and an intact structure in aqueous solutions with pH ranging from 4.0 to 7.7. Given its exceptional stability and pH-dependent fluorescence intensity, Al-MIL-101-NH2 has been applied to fluorescent pH sensing. Significantly, in the whole experimental pH range (4.0-7.7), the fluorescence intensity almost increases with increasing pH (R(2) = 0.99688) which can be rationalized using a linear equation: I = 2.33 pH + 26.04. In addition, error analysis and cycling experiments have demonstrated the accuracy and utilizability of the sensor. In practical applications (PBS and lake water), Al-MIL-101-NH2 also manifests its analytical efficiency in pH sensing. And the samples can be easily isolated from an aqueous solution by incorporating Fe3O4 nanoparticles. Moreover, the possible sensing mechanism based on amino protonation is discussed in detail. This work is on of the few cases for integrated pH sensing systems in aqueous solution based on luminescent MOFs. PMID- 27002861 TI - Two phases of aging separated by the Smurf transition as a public path to death. AB - Aging's most obvious characteristic is the time dependent increase of an individual's probability to die. This lifelong process is accompanied by a large number of molecular and physiological changes. Although numerous genes involved in aging have been identified in the past decades its leading factors have yet to be determined. To identify the very processes driving aging we have developed in the past years an assay to identify physiologically old individuals in a synchronized population of Drosophila melanogaster. Those individuals show an age dependent increase of intestinal permeability followed by a high risk of death. Here we show that this physiological marker of aging is conserved in 3 invertebrate species Drosophila mojavensis, Drosophila virilis, Caenorhabditis elegans as well as in 1 vertebrate species Danio rerio. Our findings suggest that intestinal barrier dysfunction may be an important event in the aging process conserved across a broad range of species, thus raising the possibility that it may also be the case in Homo sapiens. PMID- 27002873 TI - The Affordable Care Act: Who Will Write the Next Chapter? PMID- 27002874 TI - Cultivating Physician Leadership Is Necessary for Lasting and Meaningful Change. PMID- 27002875 TI - Slowing Medical Education Through Schwartz Center Rounds. PMID- 27002876 TI - In Reply to Ho. PMID- 27002877 TI - Bolstering the Biosocial Paradigm: The Next Steps in Medical Education and Practice. PMID- 27002878 TI - In Reply to Agonafer and Bui. PMID- 27002879 TI - Creating a Humanistic Surgical Theater: The Patient-Centered Pause. PMID- 27002880 TI - Social Science and Humanities Research in MD-PhD Training. PMID- 27002881 TI - Intellectual Virtue Vaccination Schedules Need to Include Boosters. PMID- 27002882 TI - In Reply to Falk. PMID- 27002883 TI - My First Hand Lessons. PMID- 27002884 TI - Three Things to Do With Stories: Using Literature in Medical, Health Professions, and Interprofessional Education. AB - It would be unusual to find a current medical school administrator or faculty member who has not heard the phrase "literature and medicine" or who does not know that literature is taught in various forms-short stories, novels, poems, essays-at many points in the curriculum at U.S. medical schools. Yet the phrase is used in slippery if not elusive ways, with no clear referent common to all who use it. This article focuses on three theoretical and pedagogical uses for literature in medical, health professions, and interprofessional education: close reading, ethical or moral inquiry, and drawing illustrations. Summaries of these approaches are provided, followed by demonstrations of how they might work in the classroom by using the story "Blankets," by Native American writer Sherman Alexie.Close reading requires reading slowly and carefully to enrich an initial encounter with a text. Ethical or moral inquiry turns to literary representations to challenge readers' assumptions and prejudices. Literature offers rich, provoking, and unusual depictions of common phenomena, so it can be used to draw illustrations. Although each approach can be used on its own, the authors argue that reading closely makes the other two approaches possible and meaningful because it shares with the diagnostic process many practices critical to skilled interprofessional caregiving: paying attention to details, gathering and reevaluating evidence, weighing competing interpretations. By modeling a close reading of a text, faculty can demonstrate how this skill, which courts rather than resists ambiguity, can assist students in making ethical and compassionate judgments. PMID- 27002885 TI - Course Offerings in the Fourth Year of Medical School: How U.S. Medical Schools Are Preparing Students for Internship. AB - The fourth year of medical school remains controversial, despite efforts to reform it. A committee from the Clerkship Directors in Internal Medicine and the Association of Program Directors in Internal Medicine examined transitions from medical school to internship with the goal of better academic advising for students. In 2013 and 2014, the committee examined published literature and the Web sites of 136 Liaison Committee on Medical Education-accredited schools for information on current course offerings for the fourth year of medical school. The authors summarized temporal trends and outcomes when available.Subinternships were required by 122 (90%) of the 136 schools and allow students to experience the intern's role. Capstone courses are increasingly used to fill curricular gaps. Revisiting basic sciences in fourth-year rotations helps to reinforce concepts from earlier years. Many schools require rotations in specific settings, like emergency departments, intensive care units, or ambulatory clinics. A growing number of schools require participation in research, including during the fourth year. Students traditionally take fourth-year clinical electives to improve skills, both within their chosen specialties and in other disciplines. Some students work with underserved populations or seek experiences that will be henceforth unavailable, whereas others use electives to "audition" at desired residency sites. Fourth-year requirements vary considerably among medical schools, reflecting different missions and varied student needs. Few objective outcomes data exist to guide students' choices. Nevertheless, both medical students and educators value the fourth year of medical school and feel it can fill diverse functions in preparing for residency. PMID- 27002886 TI - Artist's Statement: N = 1: An Internal Struggle. PMID- 27002887 TI - The Letters of Anton Chekhov Letters of Anton Chekhov Doctor Chekhov: A Study in Literature and Medicine [Excerpts]. PMID- 27002889 TI - The Gold-Hope Tang, MD 2015 Humanism in Medicine Essay Contest: Third Place: Gauze and Guns. PMID- 27002890 TI - Stillborn. PMID- 27002891 TI - Going "Fourth" From Medical School: Fourth-Year Medical Students' Perspectives on the Fourth Year of Medical School. AB - PURPOSE: To learn what graduating medical students considered the primary purposes of the fourth year of medical school, their approach to residency selection, and the challenges they faced in meeting their fourth-year goals. METHOD: A 52-question Web-based survey was administered to fourth-year students from 20 U.S. MD-granting medical schools in spring 2014. Quantitative data were analyzed with one-way analysis of variance, chi-square analysis, or paired t tests. Responses to an open-ended question were coded into themes and confirmed. RESULTS: A total of 1,367/2,884 (47.4%) students responded. Students applied to a mean of 36.4 (SD = 22.6) residency programs and interviewed at a mean of 12.3 (SD = 5.6) programs. Surgery applicants applied to more programs (mean = 58.2, SD = 22.3; P < .001); radiology applicants interviewed at more programs (mean = 16.9, SD = 8.5; P < .001). Students took a mean of 1.8 (SD = 0.8) monthlong away electives in their career specialty of choice; surgery and emergency medicine applicants were more likely to complete away electives (P < .001). Students agreed the fourth year has multiple valuable purposes, including maximizing the likelihood of matching into their residency of choice, gaining a broad educational experience, and preparing for residency. The main purpose varied by specialty, but overall students ranked preparing for residency highest. Completing away electives and interviewing were expensive; approximately 35% of students could not complete away electives because of financial constraints. CONCLUSIONS: Medical students view the fourth year as a time for residency selection and preparation. PMID- 27002892 TI - Effect of yeast biomass with high content of carotenoids on erythrocyte deformability, NO production and Na,K-ATPase activity in healthy and LPS treated rats. AB - Measurements of red blood cell (RBC) deformability together with estimation of NO synthase activity and Na,K-ATPase activity were used for characterization of RBC functionality in rats subjected to single dose of Escherichia coli lipopolysaccharides (LPS) at a dose of 1 mg/kg. We hypothesized that LPS might initiate a malfunction of RBC. We also investigated the potential effect of carotenoids (10 mg/kg/day) produced in red yeast biomass of Rhodotorula glutinis on RBC in LPS-challenged rats. LPS significantly reduced the deformability of RBC (by 14%) together with decrease of NO-synthase activity by 20%. Daily supplementation of carotenoids for 10 days attenuated the LPS-induced injury, as observed by 22% increase of RBC deformability and 23% increase of NO-synthase activity. The activity of Na,K-ATPase was also improved probably due to increased number of active enzyme molecules as indicated by 66% enhancement of Vmax value, hence maintaining the activity of erythrocyte Na,K-ATPase to the level even higher as compared with healthy control animals. It may be concluded that administration of yeast biomass with high content of carotenoids resulted in advanced function of erythrocytes as concerns their ability to squeeze through narrow capillaries of the circulation, better intrinsic production of NO and improvement of intracellular homeostasis of sodium. PMID- 27002893 TI - Effect of endoleaks on changes in aortoiliac volume after endovascular repair for abdominal aortic aneurysm. AB - PURPOSE: To evaluate changes in aortoiliac volume after endovascular repair (EVAR) for abdominal aortic aneurysm (AAA) in patients with and without endoleaks. MATERIALS AND METHODS: We retrospectively analyzed 137 patients who underwent EVAR for AAA. We manually measured the aortoiliac volume on pre procedural baseline CT angiograms (CTAs) and post-procedural follow-up CTAs. All post-procedural CTAs were evaluated for the presence of endoleaks. Follow-up examinations were grouped into five time points relative to the date of the EVAR procedure and mean aortoiliac volume changes from the baseline were calculated. RESULTS: In 51 patients (37.2%), endoleaks were detected during follow-up. In patients without any endoleaks, mean aortoiliac volume decreased by 21.1% from the pre-interventional baseline examination to the last follow-up examination. In patients with any endoleak during follow-up aortoiliac volume increased by 12.2% and in patients with only transient, post-procedural endoleaks (n = 18), aortoiliac volume decreased by 13.4% over the same time period. CONCLUSION: After EVAR for AAA, aortoiliac volume on CT angiography decreases by approximately 20% over time in the absence of endoleaks and increases in the presence of endoleaks. Transient post-procedural endoleaks, however, do not influence long-term volume regression. PMID- 27002894 TI - Elevated red blood cell distribution width is associated with liver function tests in patients with primary hepatocellular carcinoma. AB - BACKGROUND: Red blood cell distribution width (RDW), a routinely tested parameter of the complete blood count (CBC), has been reported to be increased in various cancers and correlated with the patients' clinical characteristics. However, the significance of RDW in primary hepatocellular carcinoma (pHCC) is largely unknown. The aim of this study was to evaluate the associations between RDW and the clinical characteristics of pHCC patients. METHODS: Medical records of 110 treatment-naive pHCC patients were retrospectively reviewed. Their clinical characteristics on admission, including RDW, liver function tests and tumor stage, were extracted, and their relationships were analyzed using Spearman correlation and Kruskal-Wallis test. Sixty-eight healthy individuals were set as controls. RESULTS: RDW was significantly increased in pHCC patients and correlated with the liver function tests. However, no correlation between RDW and tumor stage was found. CONCLUSION: RDW may be used to assess the liver function, but not the tumor stage in pHCC patients. PMID- 27002895 TI - Hemorheological in vitro action of propofol on erythrocytes from healthy donors and diabetic patients. AB - Drugs used during anesthesia might induce disturbance on microcirculation due to their systemic cardiovascular actions and to direct hemorheological effects. A comparative investigation of the hemorheological alterations related to in vitro propofol treatment of red blood cells (RBCs) from healthy and diabetic volunteers is presented here. Viscoelasticity and aggregation of RBCs from type 2 diabetic patients (DBT) and healthy donors (HD) were studied from RBCs incubated with propofol near steady-state concentration. 'S parameter', which measures the aggregation degree, was obtained using digital analysis of microscopic images. Erythrocyte viscoelasticity parameters were determined using an Erythrocyte Rheometer. Results obtained from DBT samples showed an increase of 10% or more in aggregation due to the propofol action. The phase shift between erythrocyte response and oscillating shear stress applied at 1 Hz was altered by propofol treatment of erythrocyte from HD and DBT. Propofol could produce slight alterations in the rheological behavior of erythrocyte from HD and DBT, at concentrations near those of steady state. Moreover, this anesthetic could induce an adverse effect in DBT, particularly on erythrocyte aggregation. The observed hemorheologic alteration would increase the possibility of microcapillary obstruction. Hence, this type of study [0] would prove relevant to avoid possible postoperative complications. PMID- 27002896 TI - Wavelet transform analysis of skin perfusion during thermal stimulation. AB - This work elucidates the mechanisms of skin microcirculation response to local heating at 44 degrees C in vasculopathic patients. Laser Doppler and tcpO2 were simultaneously acquired. Patients were selected on the basis of tcpO2: Group A <30 mmHg; Group B 30-50 mmHg; Group C >50 mmHg. The wavelet analysis of signal oscillations displays six frequency intervals. Each interval is assigned to a specific cardiovascular activity. The contributions of cardiac, myogenic and neurogenic activities were selectively detected. Thermal stimulation increased relative amplitude in all patients: heart activity by +103.26% in A, +162.84% in B, +454.54% in C; myogenic activity by +52.45% in A, +38.51% in B, +156.19% in C; neurogenic activity +43.36% in A, +74.15% in B, +242.42% in C. Thermal stimulation increased relative power in all patients: heart activity by +365.30% in A, +473.72% in B, +1393.77% in C; myogenic activity by +106.92% in A, +66.03% in B, +380.18% in C; neurogenic activity by +77.00% in A, +162.65% in B, +771.93% in C.This work demonstrates that the spectral analysis allows extracting from Laser Doppler signals more information than that can be gained by solely investigating perfusion values over time. PMID- 27002898 TI - Synthesis of the Strychnos Alkaloid (-)-Strychnopivotine and Confirmation of its Absolute Configuration. AB - The first enantioselective synthesis of (-)-strychnopivotine from a known and inexpensive phenol has been achieved in 15 steps. The strategy is based on a new diastereoselective aza-Michael-enol-ether cascade desymmetrization of a dienone, guided by a removable lactic acid-derived chiral auxiliary. Synthesis involves a phenol dearomatization, a conjugated silicon addition, a stereoselective double reductive amination, and two Heck-type carbopalladations as key steps. The absolute configuration of the natural compound, which, to date, has been uncertain, was confirmed by using circular dichroism (CD) spectroscopy and X-ray analyses. PMID- 27002899 TI - Inflammation, lipids and aortic intima-media thickness in newborns following chorioamnionitis. AB - AIM: This study investigated whether chorioamnionitis was associated with increased inflammation, dyslipidaemia and adverse cardiovascular phenotypes in the immediate postnatal period. METHODS: This prospective case-control study included preterm infants (30(+0) -35(+6) weeks gestational age, GA) whose mothers did not have pregnancy-related conditions that may influence outcomes. Chorioamnionitis was diagnosed by placental histology, and infants were divided retrospectively into cases (chorioamnionitis-exposed) and controls (unexposed). Serum high-sensitivity C-reactive protein (hsCRP), lipid profile, far-wall abdominal aortic intima-media thickness (aIMT) and blood pressure (BP) were measured in the first week of life. RESULTS: There were 20 (16 male, mean GA 32.4 weeks) cases and 31 (12 male, mean GA 32.6 weeks) controls. Histological chorioamnionitis was associated with a significant increase in hsCRP and a non significant trend towards an adverse lipid profile. There was no evidence of differences in aIMT or BP. CONCLUSION: Preterm infants exposed to chorioamnionitis have greater postnatal inflammation. There were no early postnatal differences in aIMT or BP. The inflammatory stimulus of chorioamnionitis late in gestation may be of insufficient intensity and duration to result in immediate postnatal alterations to arterial structure. Cardiovascular follow-up of infants exposed to chorioamnionitis may identify differential risk trajectories and subsequent inflammatory responses. PMID- 27002900 TI - Photon source term after single collision in targets of silicon, copper and lead for 50-500 keV X-ray beams. AB - Single-scattered X-ray doses at 1 m from silicon, copper and lead targets were calculated using an analytical point-kernel method considering the self absorption, and the calculated values were compared with detailed results of a Monte Carlo calculation with respect to the emission angle. In the calculations, a slab slanted at 3 degrees to the beam axis was used for silicon in addition to the cylindrical targets for the three materials, and the slab geometry showed the largest doses. The analytical calculations were underestimated compared with the Monte Carlo calculations by less than 24% for silicon and 40% for copper, particularly at large-angle scattering, which was attributable to the buildup effect of the single-scattered X-rays in the targets. By considering the buildup effect, the difference from Monte Carlo results decreased to less than 20%. For lead, the influence of fluorescent X-rays produced by the source beam was dominant in the backward direction, which was also calculated analytically. The simple analytical program can be applied to any target size and shape by considering self-absorption and the buildup effect, both of which inform the simple dose estimation method. PMID- 27002901 TI - Monte-Carlo simulation of a slot-scanning digital mammography system for tomosynthesis. AB - BACKGROUND: Digital breast tomosynthesis (DBT) reconstructs planar slices of the breast based on two-dimensional angular projections. Early studies and clinical trials show that DBT is an improvement over full field digital mammography (FFDM) because it provides the radiologist with better image quality and more information. OBJECTIVE: This paper presents a simulation system to model the performance of a slot-scanning FFDM and DBT system. METHODS: A tissue-equivalent three dimensional (3D) breast phantom was constructed, validated for slot scanning digital mammography and used in simulating digital breast tomosynthesis. The simulation system was validated by comparing images acquired with a slot scanning mammography machine with simulated phantom images, using the edge-test method and image quality metrics modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE). Different two-dimensional (2D) projections of the 3D phantom were simulated and the phantom was reconstructed using filtered backprojection. RESULTS: Image quality metrics showed equivalence between simulated and real images. CONCLUSIONS: The simulation tool is suitable for slot-scanning FFDM and DBT and may be used for the design and comparison of mammography systems. PMID- 27002902 TI - Temporal sparsity exploiting nonlocal regularization for 4D computed tomography reconstruction. AB - X-ray imaging applications in medical and material sciences are frequently limited by the number of tomographic projections collected. The inversion of the limited projection data is an ill-posed problem and needs regularization. Traditional spatial regularization is not well adapted to the dynamic nature of time-lapse tomography since it discards the redundancy of the temporal information. In this paper, we propose a novel iterative reconstruction algorithm with a nonlocal regularization term to account for time-evolving datasets. The aim of the proposed nonlocal penalty is to collect the maximum relevant information in the spatial and temporal domains. With the proposed sparsity seeking approach in the temporal space, the computational complexity of the classical nonlocal regularizer is substantially reduced (at least by one order of magnitude). The presented reconstruction method can be directly applied to various big data 4D (x, y, z+time) tomographic experiments in many fields. We apply the proposed technique to modelled data and to real dynamic X-ray microtomography (XMT) data of high resolution. Compared to the classical spatio temporal nonlocal regularization approach, the proposed method delivers reconstructed images of improved resolution and higher contrast while remaining significantly less computationally demanding. PMID- 27002903 TI - Ordered-subset Split-Bregman algorithm for interior tomography. AB - Inspired by the Compressed Sensing (CS) theory, it has been proved that the interior problem of computed tomography (CT) can be accurately and stably solved if a region-of-interest (ROI) is piecewise constant or polynomial, resulting in the CS-based interior tomography. The key is to minimize the total variation (TV) of the ROI under the constraint of the truncated projections. Coincidentally, the Split-Bregman (SB) method has attracted a major attention to solve the TV minimization problem for CT image reconstruction. In this paper, we apply the SB approach to reconstruct an ROI for the CS-based interior tomography assuming a piecewise constant imaging model. Furthermore, the ordered subsets (OS) technique is used to accelerate the convergence of SB algorithm, leading to a new OS-SB algorithm for interior tomography. The conventional OS simultaneous algebraic reconstruction technique (OS-SART) and soft-threshold filtering (STF) based OS SART are also implemented as references to evaluate the performance of the proposed OS-SB algorithm for interior tomography. Both numerical simulations and clinical applications are performed and the results confirm the advantages of the proposed OS-SB method. PMID- 27002904 TI - X-ray CT geometrical calibration via locally linear embedding. AB - For X-ray computed tomography (CT), geometric calibration and rigid patient motion compensation are inter-related issues for optimization of image reconstruction quality. Non-calibrated system geometry and patient movement during a CT scan will result in streak-like, blurring and other artifacts in reconstructed images. In this paper, we propose a locally linear embedding based calibration approach to address this challenge under a rigid 2D object assumption and a more general way than what has been reported before. In this method, projections are linearly represented by up-sampled neighbors via locally linear embedding, and CT system parameters are iteratively estimated from projection data themselves. Numerical and experimental studies show that images reconstructed with calibrated parameters are in excellent agreement with the counterparts reconstructed with the true parameters. PMID- 27002905 TI - Quantification of fat deposition in bone marrow in the lumbar vertebra by proton MRS and in-phase and out-of-phase MRI for the diagnosis of osteoporosis. AB - The goal for this study was to investigate if proton MRS (1H-MRS) and out-of phase and in-phase MRI can quantify the fat deposition in bone marrow within the lumbar vertebra that can be used to distinguish well between osteoporosis patients and healthy control subjects. Sixty-eight subjects participated in this study. The diagnostic results from dual-energy x-ray absorptiometry served as the gold standard, which was able to separate the subjects into osteoporosis (38 subjects) and non-osteoporosis group (30 subjects). Then the 68 subjects were further scanned by 1H-MRS and in-phase and out-of-phase MRI and the findings from the imaging methods were also compared and analyzed. It was found that the measured signal intensity ratio (SIR), lipid-water ratio (LWR) and fat fraction (FF) in L2 vertebra from the two imaging methods were able to identify the fat deposition in bone marrow, which could be used to diagnose osteoporosis. Diagnostic accuracy for osteoporosis based on identified SIR, LRW and FF was analyzed by using ROC curves. Our findings suggested that statistically significant differences were identified between osteoporosis patients and healthy subjects. The sensitivity and specificity equal to 78.9% and 75.9% for SIR, 79.2% and 66.7% for LRW, 71.4% and 72.4% for FF, can be achieved when fat deposition related parameters in bone marrow from the lumbar vertebra are used as classifiers. Our results showed that fat deposition-related parameters including fat content in bone marrow and water content in the lumbar vertebra are clearly different between the osteoporosis and non-osteoporosis group, suggesting that both 1H-MRS and in-phase and out-of-phase MRI can be used for diagnosing osteoporosis and monitoring its progression. PMID- 27002906 TI - Influence of the X-ray beam quality on the dose increment in CT with iodinated contrast medium. AB - BACKGROUND: In computed tomography (CT), the image contrast is given by the difference in X-ray attenuation in the various tissues of the patient and contrast media are used to enhance image contrast in anatomic regions characterized by similar attenuation coefficients. OBJECTIVE: Aim of the present work is to enlarge the range of applicability of the method previously introduced for organ dosimetry in contrast-enhanced CT, by studying the effects of X-ray beam quality on the parameters of the model. Furthermore, an experimental method for the evaluation of the attenuation properties of iodinated solutions is proposed. METHODS: Monte Carlo simulations of anthropomorphic phantoms were carried out to determine a bi-parametrical (a and b) analytical relationship between iodine concentration and dose increase in organs of interest as a function of the tube kilo-voltage peak potential (kVp) and filtration. Experimental measurements of increments in Hounsfield Units (HU) were conducted in several CT scanners, at all the kVp available, in order to determine the parameter gamma which relates the HU increment with the iodine mass fraction. A cylindrical phantom that can be filled with iodine solutions provided with an axial housing for a pencil ionization chamber was designed and assembled in order to measure the attenuation properties of iodine solutions under irradiation of a CT scanner and to obtain a further validation of Monte Carlo simulations. RESULTS: The simulation-derived parameters of the model, a and b, are only slightly dependent upon the tube kilo-voltage peak potential and filtration, while such scanner-dependent features influence mainly the experimentally-derived gamma parameter. Relative dose variations registered by the ionization chamber inside the iodine-filled cylindrical phantom decrease when the X-ray mean energy increases, and reaches about 50% for 10 mg/ml of iodine. CONCLUSIONS: The dosimetric method for contrast-enhanced CT can be applied to all CT scanners by adopting average simulative parameters and by carrying out a simple measurement with a series of iodine contrast solutions. The novel experimental methodology introduced can provide a direct measurement of iodine attenuation properties. PMID- 27002907 TI - Development of multimodal neuroimaging markers for neurological disorders - Part 1. PMID- 27002908 TI - Basal vein in the posterior incisural space: An anatomical comparison based on autopsy, digital subtraction angiography and computed tomographic venography. AB - BACKGROUND: During surgical procedures, the basal vein in the posterior incisural space is susceptible to obstruction. In such circumstances, venous infarction can occur along with venous damage. OBJECTIVE: The aim of this study was to correlate the microanatomy of the basal vein in the posterior incisural space with the digital subtraction angiography (DSA) and computed tomographic venography (CTV). METHODS: Twenty cadavers and 42 patients were examined in this study. The head of each cadaver was injected with blue-colored gelatin via the internal jugular veins. Venograms for each patient were obtained from the venous phases of DSA or CTV. RESULTS: Compared to the cadavers, in the patients, DSA and CTV revealed 90% and 95% of the basal vein, respectively. According to difference of entrance, three types of basal veins were identified. No statistical difference of typing was found among the cadavers, DSA images and CTV images. On three sides of the cadavers and one side of the CTV images, the basal vein entered the straight sinus through the meningeal vein in the tentorium cerebelli. CONCLUSIONS: Preoperative DSA and CTV are useful in the design of individualized surgical approaches and the preservation of the basal vein in the posterior incisural space. PMID- 27002909 TI - Differentially disrupted functional connectivity of the subregions of the amygdala in Alzheimer's disease. AB - The amygdala is an important brain area involved in cognitive procession and emotional regulation. Previous studies have typically considered the amygdala as a single structure, which likely masks contribution of individual amygdala subdivisions. Actually, the amygdala is heterogeneous and composed of structurally and functionally distinct nuclei, which may present different connectivity patterns and predict to relevant cognitive deficits in Alzheimer's disease (AD). However, little is known about functional connectivity of amygdala subregions in the resting state in AD subjects. Here, we employed resting-state functional MRI (fMRI) to examine functional connectivity changes of subregions comparing the AD patients with the age-matched control subjects. Thirty-two AD and 38 control subjects were analyzed. We defined three subregions of the amygdala according to probabilistic cytoarchitectonic atlases and mapped the whole-brain resting-state functional connectivity for each subregion: The central medial nucleus (CM) of amygdala exhibited connections with the lentiform nucleus, parahippocampus and lateral temporal gyrus; the lateral basal nucleus (LB) of amygdala functionally connected with the parahippocampus, lateral temporal gyrus, middle occipital gyrus and medial prefrontal cortex; and the superficial nucleus (SF) of amygdala had connection with the parahippocampus, lentiform nucleus, lateral temporal gyrus, insula, middle occipital gyrus, precentral and postcentral gyrus. Comparing with the controls, the AD patients presented disrupted connectivity patterns in the LB of amygdala, which predicted disconnection with the left uncus, right insula, right precentral gyrus, the left superior temporal gyrus and right claustrum. These findings in a large part supported our hypothesis and provided a new insight in understanding the pathophysiological mechanisms of AD. PMID- 27002910 TI - Cerebral activation effects of acupuncture using Zusanli (ST36) and Yanglingquan (GB34) points based on Regional Homogeneity indices: A resting-state fMRI study. AB - OBJECTIVE: This study aimed to observe the cerebral activation effects of acupuncturing the Zusanli (ST36) plusYanglingquan (GB34) points in young healthy volunteers based on Regional Homogeneity (ReHo) indices. METHODS: Ten healthy volunteers were enrolled, including 4 males and 6 females between the ages 20 and 34 years with a median age of 23 years. Magnetic resonance imaging (GE Signa HDxt 3.0T) was performed in four groups: Before acupuncture (Control Group), after acupuncture at Zusanli (ST36 Group), after acupuncture at Yanglingquan (GB34 Group) and after acupuncture at both Zusanli and Yanglingquan (Compatibility Group). Differences in the brain ReHo indices of the 4 groups were analyzed by statistical parametric mapping (SPM8) and ReHo data processing methods. The significantly different brain regions were obtained using a false discovery rate correction (FDR-Corrected). RESULTS: The ReHo indices revealed that the main significant effect was in the Compatibility Group. Compared with the resting state of the Control Group, the ReHo values of the Compatibility Group increased in the right middle frontal gyrus (BA8, 9), left superior temporal areas (BA22), ventral anterior cingulate area (BA24) and right inferior parietal lobe (BA40); in contrast, the ReHo values decreased in the left thalamus, right insular cortex (BA13), left inferior frontal lobe (BA9) and right dorsal anterior cingulate area (BA32). Our analysis showed that the Compatibility Group had higher ReHo values than the left inferior parietal lobule (BA40) and right frontal cortex (BA6) of the ST36 Group and the posterior lobe of the right cerebellum, dorsal anterior cingulate (BA32), left and right middle frontal gyrus (BA46, BA9), left precuneus (BA7), right inferior parietal love (BA40) of the GB34 Group. CONCLUSION: The results of our neuroimaging study suggest that the combination of acupoints could more widely activate areas of the brain compared to a single acupoint. Additionally, the combination of acupoints can activate some new brain areas and generate new curative effects. PMID- 27002911 TI - The changes of HRV in refractory epilepsy: The potential index to predict the onset of epilepsy in children. AB - In this study, we examine the potential of heart rate variability (HRV) as an efficient tool for predicting the onset of epilepsy in children. We totally collected 53 seizures EEG and ECG data using Video - EEG - ECG monitoring system. We then separated the ECG data into three segments: ten-minute before onset of each seizure, five-minute before onset of each seizure, and five-minute from the onset of each seizure. After the HRV parameters in all segments were calculated, we compared the differences between pre-ictal period and ictal period. We found that the values of meanHR, LF and LF/HF were greater in onset period. And the values of meanRR and the HF were less in ictal period. And it presented the similar changes when seizures occurred in the daytime and seizures occurred in the nighttime. In brief, we found that the sympathetic nervous system was under a more active status during onset period. We speculated that the HRV parameters such as the LF, HF or LF/HF could have potential to predict the seizures in children with epilepsy. PMID- 27002912 TI - Altered regional homogeneity in epileptic patients with infantile spasm: A resting-state fMRI study. AB - Infantile spasm (IS) syndrome is an age-related epileptic encephalopathy that occurs in children. The purpose of this study was to investigate regional homogeneity (ReHo) changes in IS patients. Resting-state fMRI was performed on 11 patients with IS, along with 35 age- and sex-matched healthy subjects. Group comparisons between the two groups demonstrate that the pattern of regional synchronization synchronization in IS patients is changed. Decreased ReHo values were found in default mode network, bilateral motor-related areas and left occipital gyrus of the patient group. Increased ReHo was found in regions of cingulum, cerebellum, supplementary motor area and brain deep nucleus, such as hippocampus, caudate, thalamus and insula. The significant differences might indicate that epileptic action have some injurious effects on the motor, executive and cognitive related regions. In addition, ReHo values of left precuneus and right superior frontal gyrus were associated with the epilepsy duration in the IS group. The correlation results indicate that the involvement of these regions may be related to the seizure generation. Our results suggest that IS may have an injurious effect on the brain activation. The findings may shed new light on the understanding the neural mechanism of IS epilepsy. PMID- 27002913 TI - Development of multimodal neuroimaging markers for neurological disorders - Part 2. PMID- 27002914 TI - Lifestyle and clinical determinants of skin autofluorescence in a population based cohort study. AB - BACKGROUND: Skin autofluorescence (SAF) is a noninvasive marker of advanced glycation end products (AGEs). In diabetes, higher SAF levels have been positively associated with long-term complications, cardiovascular morbidity and mortality. Because little is known about the factors that influence SAF in nondiabetic individuals, we assessed the association of clinical and lifestyle parameters with SAF as well as their interactions in a large-scale, nondiabetic population and performed the same analysis in a type 2 diabetic subgroup. METHODS: In a cross-sectional study in participants from the LifeLines Cohort Study, extensive clinical and biochemical phenotyping, including SAF measurement, was assessed in 9009 subjects of whom 314 (3.5%) subjects with type 2 diabetes. RESULTS: Mean SAF was 2.04 +/- 0.44 arbitrary units (AU) in nondiabetic individuals and 2.44 +/- 0.55 AU in type 2 diabetic subjects (P < 0.0001). Multivariate backward regression analysis showed that in the nondiabetic population, SAF was significantly and independently associated with age, BMI, HbA1c, creatinine clearance, genetic polymorphism in NAT2 (rs4921914), current smoking, pack-years of smoking and coffee consumption. In the type 2 diabetic group, a similar set of factors was associated with SAF, except for coffee consumption. CONCLUSIONS: In addition to the established literature on type 2 diabetes, we have demonstrated that SAF levels are associated with several clinical and lifestyle factors in the nondiabetic population. These parameters should be taken into consideration when using SAF as a screening or prediction tool for populations at risk for cardiovascular disease and diabetes. PMID- 27002915 TI - Green synthesis of nanosilver particles by Aspergillus terreus HA1N and Penicillium expansum HA2N and its antifungal activity against mycotoxigenic fungi. AB - AIMS: The aim of this study was to synthesize silver nanoparticles (AgNPs) by an eco-friendly and low-cost method using the fungi Aspergillus terreus HA1N and Penicillium expansum HA2N as an alternative to chemical procedures mostly requiring drastic experimental conditions emitting toxic chemical byproducts. Also, this study has been extended to evaluate the effect of AgNPs on the growth of some mycotoxigenic fungi and ochratoxin A (OTA) produced by Aspergillus ochraceus. METHODS AND RESULTS: The AgNPs have been characterized by UV-Visible Spectrophotometer, Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR) and Transmission Electron Microscope (TEM). The TEM analysis has revealed that the size of AgNPs ranged between 14 and 25 nm in the case of P. expansum and 10-18 nm in the case of A. terreus. The antifungal activity of AgNP colloids has indicated that the highest inhibition zone was detected with AgNPs synthesized by A. terreus HA1N against all tested fungi. The highest inhibition zone was detected with Aspergillus niger at concentrations 3 and 6 MUg of AgNP solution (7.56 +/- 0.38 and 11.3 +/- 1.8 mm, respectively) while, A. ochraceus showed the maximum inhibition zone (16.33 +/- 0.96 mm) at the concentration 9 MUg of AgNPs synthesized by A. terreus. The results have also indicated that the AgNPs synthesized by A. terreus and P. expansum at the concentration 220 MUg/100 ml media gave the highest reduction of OTA, where the percentages of reduction were 58.87 and 52.18% respectively. CONCLUSIONS: The smallest size AgNPs synthesized by A. terreus HA1N are better in their antifungal activity against all tested mycotoxigenic fungi than the largest one synthesized by P. expansum HA2N. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study focused on using AgNPs in control of OTA production. PMID- 27002916 TI - Analysis of Risk Factors for Abnormal Pulmonary Function in Pediatric Cancer Survivors. AB - BACKGROUND: Childhood cancer survivors are at increased risk for pulmonary related morbidity and mortality. The Children's Oncology Group Long-Term Follow Up (COG-LTFU) guidelines recommend pulmonary function testing after treatment with bleomycin, busulfan, carmustine, lomustine, thoracic radiation, bone marrow transplant, or pulmonary surgery. The aim of this analysis was to determine the prevalence of pulmonary function abnormalities in a pediatric survivor cohort. PROCEDURE: Patients >=5 years old seen in our survivor clinic with at least one exposure outlined by COG-LFTU Guidelines were included. Original pulmonary function test (PFT) results were obtained and blindly reinterpreted by a single reviewer. Demographic, diagnosis, treatment factors, and clinical and/or patient reported symptoms of cough, wheeze, and/or dyspnea were abstracted from their medical record. RESULTS: Overall, 143 (63.3%) survivors had PFT results available; 55.2% were male, 49.7% were white, and the mean age was 14.1 +/- 4.8 years. Abnormal PFTs were found in 65.0% (n = 93) with 21.0% having multiple abnormalities. Specifically, 41.3% had hyperinflation, 25.9% had obstructive, and 13.3% had restrictive disease. Patients diagnosed at <5 years were more likely to have a pulmonary abnormality (P = 0.04); a majority of those diagnosed <5 years underwent pulmonary surgery or thoracic radiation. Regardless of the presence of a PFT abnormality, more than 80% of survivors were asymptomatic (82.9% vs.81.5%; P-value = 0.54). CONCLUSIONS: Almost two-thirds of survivors screened per the COG LTFU Guidelines had an abnormal PFT but a majority reported no clinical symptoms. Hyperinflation was the most prevalent abnormality. PMID- 27002917 TI - Modified Activation Technique for Nasal Stent of Nasoalveolar Molding Appliance for Columellar Lengthening in Bilateral Cleft Lip/Palate. AB - Bilateral cleft lip/cleft palate is associated with nasal deformities typified by a short columella. The presurgical nasoalveolar molding (NAM) therapy approach includes reduction of the size of the intraoral alveolar cleft as well as positioning of the surrounding deformed soft tissues and cartilages. In a bilateral cleft patient, NAM, along with columellar elongation, eliminates the need for columellar lengthening surgery. Thus the frequent surgical intervention to achieve the desired esthetic results can be avoided. This article proposes a modified activation technique of the nasal stent for a NAM appliance for columellar lengthening in bilateral cleft lip/palate patients. The design highlights relining of the columellar portion of the nasal stent and the wire bending of the nasal stent to achieve desirable results within the limited span of plasticity of the nasal cartilages. With this technique the vertical taping of the premaxilla to the oral plate can be avoided. PMID- 27002918 TI - Hydrogen Attachment/Abstraction Dissociation (HAD) of Gas-Phase Peptide Ions for Tandem Mass Spectrometry. AB - Dissociation of gas-phase peptide ions through interaction with low-energy hydrogen (H) radical (~0.15 eV) was observed with a quadrupole ion trap mass spectrometry. The H radical generated by thermal dissociation of H2 molecules passing through a heated tungsten capillary (~2000 degrees C) was injected into the ion trap containing target peptide ions. The fragmentation spectrum showed abundant c-/z- and a-/x-type ions, attributable to H attachment/abstraction to/from peptide ion. Because the low-energy neutral H radical initiated the fragmentation, the charge state of the precursor ion was maintained during the dissociation. As a result, precursor ions of any charge state, including singly charged positive and negative ions, could be analyzed for amino acid sequence. The sequence coverage exceeding 90% was obtained for both singly protonated and singly deprotonated substance P peptide. This mass spectrometry also preserved labile post-translational modification bonds. The modification sites of triply phosphorylated peptide (kinase domain of insulin receptor) were identified with the sequence coverage exceeding 80%. PMID- 27002919 TI - Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction. AB - The diabetic foot ulcer (DFU) is the leading cause of lower extremity amputation worldwide and is directly associated with comorbidity, disability and mortality. Oxidative stress mechanisms have been implicated in the pathogenesis of these wounds. Intra-lesional infiltration of epidermal growth factor has emerged as a potential therapeutic alternative to allow for physiological benefit while avoiding the proteolytic environment at the centre of the wound. The aim of this study was to characterise the response of patients with DFUs to epidermal growth factor treatment in terms of redox status markers. Experimental groups included patients with DFUs before and 3-4 weeks after starting treatment with epidermal growth factor; compensated and non-compensated diabetic patients without ulcers; and age-matched non-diabetic subjects. Evaluations comprised serum levels of oxidative stress and antioxidant reserve markers. Patients with DFUs exhibited the most disheveled biochemical profile, with elevated oxidative stress and low antioxidant reserves, with respect to non-ulcerated diabetic patients and to non diabetic subjects. Epidermal growth factor intra-lesional administration was associated with a significant recovery of oxidative stress and antioxidant reserve markers. Altogether, our results indicate that epidermal growth factor intra-ulcer therapy contributes to restore systemic redox balance in patients with DFUs. PMID- 27002920 TI - Potent Antigen-Adjuvant Delivery System by Conjugation of Mycobacterium tuberculosis Ag85B-HspX Fusion Protein with Arabinogalactan-Poly(I:C) Conjugate. AB - Protein-based vaccine is promising to improve or replace Mycobacterium bovis BCG vaccine for its specificity, safety, and easy production. However, protein-based vaccine calls for potent adjuvants and improved delivery systems to protect against Mycobacterium tuberculosis. Poly(I:C) is one of the most potent pathogen associated molecular patterns that signals primarily via TLR3. Arabinogalactan (AG) is a biocompatible polysaccharide that can increase splenocyte proliferation and stimulate macrophages. The AG-poly(I:C) conjugate (AG-P) showed an adjuvant potency through a synergistic interaction of AG and poly(I:C). Ag85B and HspX are two important virulent protein antigens of Mycobacterium tuberculosis and Ag85B HspX fusion protein (AH) was prepared. An antigen-adjuvant delivery system (AH-AG P) was developed by conjugation of AH with AG-P to ensure that both AH and AG-P reach the APCs simultaneously. AH-AG-P elicited high AH-specific IgG titers and stimulated lymphocyte proliferation. AH-AG-P provoked the secretion of Th1-type cytokines (TNF-alpha, IFN-gamma, and IL-2) and Th2-type cytokines (IL-4 and IL 10). Pharmacokinetics revealed that conjugation with AG-P could prolong the serum exposure of AH to the immune system. Pharmacodynamics suggested that conjugation with AG-P led to a rapid and intense production of AH-specific IgG. Accordingly, conjugation with AG-P could promote a robust cellular and humoral immune response to AH. Thus, conjugation of AH with a potent adjuvant AG-P is an effective strategy to develop an efficacious protein-based vaccine against Mycobacterium tuberculosis. PMID- 27002922 TI - Layer-by-Layer Assembly of Multifunctional Flame Retardant Based on Brucite, 3 Aminopropyltriethoxysilane, and Alginate and Its Applications in Ethylene-Vinyl Acetate Resin. AB - An efficient and multifunctional brucite/3-aminopropyltriethoxysilane (APTES)/nickel alginate/APTES (B/A/Nia/A) hybrid flame retardant was fabricated via the layer-by-layer assembly technique with brucite, silane coupling agents, nickel chloride, and sodium alginate. The morphology, chemical composition, and structure of the hybrid flame retardant were characterized. The results confirmed the multilayer structure and indicated that the assembled driving forces were electrostatic interactions, dehydration condensation, hydrogen bonds, and coordination bonds. When used in ethylene-vinyl acetate (EVA) resin, the multifunctional flame retardant had better performance than brucite in improving the flame retardancy, smoke suppression, and mechanical properties. With 130 phr loading, the multifunctional flame retardant achieved a limiting oxygen index value of 32.3% and a UL 94 V-0 rating, whereas the brucite achieved only 31.1% and a V-2 rating, respectively. The peak heat release rate and total heat released decreased by 41.5% and 8.9%, respectively. The multifunctional flame retardant had an excellent performance in reducing the smoke, CO, and CO2 production rates. These improvements could be attributed to the catalyzing carbonization of nickel compounds and the formation of more protective char layers. Moreover, the elongation at break increased by 97.5%, which benefited from the improved compatibility and the sacrificial bonds in the nickel alginate. The mechanism of flame retardant, smoke suppression, and toughening is proposed. PMID- 27002921 TI - Evaluation of allogeneic transplantation in first or later minimal residual disease - negative remission following adult-inspired therapy for acute lymphoblastic leukemia. AB - Comparisons without hematopoietic cell transplantation (HCT) to myeloablative (MAC) or reduced-intensity HCT (RIC) for adults with acute lymphoblastic leukemia (ALL) in first minimal-residual-disease negative remission (MRD(Neg) CR1) are limited. Further, the importance of MRD(Neg) following salvage therapy (MRD(Neg) CR2+) is unknown. We evaluated 89 patients in MRD(Neg) CR1 after adult-inspired treatment: 33 received MAC (12 Philadelphia chromosome [Ph]+), 17 received RIC (13 Ph+), and 39 Deferred HCT (3 Ph+). Three-year overall survival (OS) estimates for MAC, RIC, and Deferred HCT were 71%, 69%, and 68%, while 3-year event-free survival (EFS) estimates were 65%, 54%, and 28%, respectively. Further, HCT in MRD(Neg) CR1 performed similarly to MRD(Neg) CR2+: 3-year OS estimates were 70% and 69%, and 3-year EFS estimates were 62% and 62%, respectively. In conclusion, adults with ALL in MRD(Neg) CR1 following adult-inspired therapy had similar OS with or without HCT, and HCT in MRD(Neg) CR2 + can yield long-term survival. PMID- 27002923 TI - Exploration of Binding Interactions of Cu(2+) with d-Penicillamine and its O- and Se- Analogues in Both Gas and Aqueous Phases: A Theoretical Approach. AB - We have theoretically explored the entire binding phenomena of d-penicillamine and its O- and Se-analogues with Cu(2+) in both gas and aqueous phases. At first, a brief conformational analysis has been performed via -XH and -COOH rotations to investigate such conformers that are suitable for binding in both bidentate as well as tridentate fashions. The stability of each bidentate and tridentate complex is determined on the basis of relative energy (DeltaE) and gas phase metal ion affinity (MIA) along with the bonding analysis by using atoms in molecule theory. The effect of conformational change on the stability of the complexes is also examined thoroughly. By analyzing the MIA values, we have shown that the side chain substitution makes an impact on the binding process. To delve into the binding phenomena in aqueous phase, we have introduced both the first and second hydration sphere models. In first hydration sphere model, to realize the precise effect of water molecules we have considered stable octahedral hexa aqua copper complex, [Cu(H2O)6](+2) and accordingly substituted water molecules depending on the bidentate or tridentate nature of the chelating agents. The influence of bulk water molecules on the energetics and geometries of the first hydrated sphere complexes have also been investigated by employing second hydration sphere model assuming physiological pH through the implementation of implicit COSMO and polarizable continuum models, respectively. In the second hydration sphere model, the zwitterionic structures of the amino acids and their side chain deprotonated forms are also included to study the binding phenomena with Cu(2+). The complete work furnishes both the binding properties and the energetics of the copper-artificial amino acid complexes in both gas and aqueous phases that will reflect a realistic overview of the entire binding phenomena. PMID- 27002924 TI - In Vitro Lesion Bypass Studies of O(4)-Alkylthymidines with Human DNA Polymerase eta. AB - Environmental exposure and endogenous metabolism can give rise to DNA alkylation. Among alkylated nucleosides, O(4)-alkylthymidine (O(4)-alkyldT) lesions are poorly repaired in mammalian systems and may compromise the efficiency and fidelity of cellular DNA replication. To cope with replication-stalling DNA lesions, cells are equipped with translesion synthesis DNA polymerases that are capable of bypassing various DNA lesions. In this study, we assessed human DNA polymerase eta (Pol eta)-mediated bypass of various O(4)-alkyldT lesions, with the alkyl group being Me, Et, nPr, iPr, nBu, iBu, (R)-sBu, or (S)-sBu, in template DNA by conducting primer extension and steady-state kinetic assays. Our primer extension assay results revealed that human Pol eta, but not human polymerases kappa and iota or yeast polymerase zeta, was capable of bypassing all O(4)-alkyldT lesions and extending the primer to generate full-length replication products. Data from steady-state kinetic measurements showed that Pol eta preferentially misincorporated dGMP opposite O(4)-alkyldT lesions with a straight chain alkyl group. The nucleotide misincorporation opposite most lesions with a branched-chain alkyl group was, however, not selective, where dCMP, dGMP, and dTMP were inserted at similar efficiencies opposite O(4)-iPrdT, O(4)-iBudT, and O(4)-(R)-sBudT. These results provide important knowledge about the effects of the length and structure of the alkyl group in O(4)-alkyldT lesions on the fidelity and efficiency of DNA replication mediated by human Pol eta. PMID- 27002926 TI - Antioxidant status in a group of institutionalised elderly people with chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is one of the most important and prevalent diseases suffered by the elderly. Evidence exists that its onset and severity might be conditioned by antioxidant status. The aim of the present study was to investigate the relationship between antioxidant status and COPD in institutionalised elderly people. In all, 183 elderly people aged >65 years (twenty-one had COPD and 160 healthy controls) were studied. The subjects' diets were investigated via the use of precise individual weighing for 7 d. Body weight, height, and biceps and triceps skinfold thickness were measured, and body fat (kg) and BMI (kg/m2) were calculated. Serum retinol, alpha-tocopherol, beta carotene and vitamin C levels were determined. Subjects with COPD ate less fruits than healthy controls (117 (sd 52) v. 192 (sd 161) g/d), their coverage of the recommended intake of vitamin C was smaller (150 (sd 45) v. 191 (sd 88) %; note that both exceeded 100 %) and their diets had a lower antioxidant capacity (6558 (sd 2381) v. 9328 (sd 5367) mmol trolox equivalent/d). Those with COPD had lower serum vitamin C and alpha-tocopherol concentrations than healthy controls (32.4 (sd 15.3) v. 41.5 (sd 14.8) umol/l and 12.1 (sd 3.2) v. 13.9 (sd 2.8) umol/l, respectively). In addition, subjects with alpha-tocopherol <14.1umol/l (50th percentile) were at 6.43 times greater risk of having COPD than those subjects with >=14.1umol/l (OR 6.43; 95 % CI 1.17, 35.24; P<0.05), taking sex, age, use of tobacco, body fat and vitamin E intake as covariables. Subjects with COPD had diets of poorer antioxidant quality, especially with respect to vitamins C and E, compared with healthy controls. PMID- 27002925 TI - Long-term neuropathological and behavioral impairments after exposure to nerve agents. AB - One of the deleterious effects of acute nerve agent exposure is the induction of status epilepticus (SE). If SE is not controlled effectively, it causes extensive brain damage. Here, we review the neuropathology observed after nerve agent induced SE, as well as the ensuing pathophysiological, neurological, and behavioral alterations, with an emphasis on their time course and longevity. Limbic structures are particularly vulnerable to damage by nerve agent exposure. The basolateral amygdala (BLA), which appears to be a key site for seizure initiation upon exposure, suffers severe neuronal loss; however, GABAergic BLA interneurons display a delayed death, perhaps providing a window of opportunity for rescuing intervention. The end result is a long-term reduction of GABAergic activity in the BLA, with a concomitant increase in spontaneous excitatory activity; such pathophysiological alterations are not observed in the CA1 hippocampal area, despite the extensive neuronal loss. Hyperexcitability in the BLA may be at least in part responsible for the development of recurrent seizures and increased anxiety, while hippocampal damage may underlie the long-term memory impairments. Effective control of SE after nerve agent exposure, such that brain damage is also minimized, is paramount for preventing lasting neurological and behavioral deficits. PMID- 27002927 TI - Transition-Metal Oxos as the Lewis Basic Component of Frustrated Lewis Pairs. AB - The reaction of oxorhenium complexes that incorporate diamidopyridine (DAP) ligands with B(C6F5)3 results in the formation of classical Lewis acid-base adducts. The adducts effectively catalyze the hydrogenation of a variety of unactivated olefins at 100 degrees C. Control reactions with these complexes or B(C6F5)3 alone did not yield any hydrogenated products under these conditions. Mechanistic studies suggest a frustrated Lewis pair is generated between the oxorhenium DAP complexes and B(C6F5)3, which is effective at olefin hydrogenation. Thus, we demonstrate for the first time that the incorporation of a transition-metal oxo in a frustrated Lewis pair can have a synergistic effect and results in enhanced catalytic activity. PMID- 27002929 TI - Japan's Public Health Paradigm: Governmentality and the Containment of Harmful Behavior. AB - In this essay, I revisit the politics of social control in the context of contemporary public health discussions, touching on the management of obesity and chronic illness. Foucault's cautionary observations regarding the infiltration of normative social values into the terrain of healing offer a productive framework for considering the politics of public health in the industrialized world. I explore Japan's public health paradigm and its key features of bureaucratic reform and health interventions through screening, socialization, education, and aggressive lifestyle training, and I consider the close proximity between health and socio-cultural values in the management of chronic conditions in Japan. PMID- 27002928 TI - X-Band Electron Paramagnetic Resonance Comparison of Mononuclear Mn(IV)-oxo and Mn(IV)-hydroxo Complexes and Quantum Chemical Investigation of Mn(IV) Zero-Field Splitting. AB - X-band electron paramagnetic resonance (EPR) spectroscopy was used to probe the ground-state electronic structures of mononuclear Mn(IV) complexes [Mn(IV)(OH)2(Me2EBC)](2+) and [Mn(IV)(O)(OH)(Me2EBC)](+). These compounds are known to effect C-H bond oxidation reactions by a hydrogen-atom transfer mechanism. They provide an ideal system for comparing Mn(IV)-hydroxo versus Mn(IV)-oxo motifs, as they differ by only a proton. Simulations of 5 K EPR data, along with analysis of variable-temperature EPR signal intensities, allowed for the estimation of ground-state zero-field splitting (ZFS) and (55)Mn hyperfine parameters for both complexes. From this analysis, it was concluded that the Mn(IV)-oxo complex [Mn(IV)(O)(OH)(Me2EBC)](+) has an axial ZFS parameter D (D = +1.2(0.4) cm(-1)) and rhombicity (E/D = 0.22(1)) perturbed relative to the Mn(IV) hydroxo analogue [Mn(IV)(OH)2(Me2EBC)](2+) (|D| = 0.75(0.25) cm(-1); E/D = 0.15(2)), although the complexes have similar (55)Mn values (a = 7.7 and 7.5 mT, respectively). The ZFS parameters for [Mn(IV)(OH)2(Me2EBC)](2+) were compared with values obtained previously through variable-temperature, variable-field magnetic circular dichroism (VTVH MCD) experiments. While the VTVH MCD analysis can provide a reasonable estimate of the magnitude of D, the E/D values were poorly defined. Using the ZFS parameters reported for these complexes and five other mononuclear Mn(IV) complexes, we employed coupled-perturbed density functional theory (CP-DFT) and complete active space self-consistent field (CASSCF) calculations with second-order n-electron valence-state perturbation theory (NEVPT2) correction, to compare the ability of these two quantum chemical methods for reproducing experimental ZFS parameters for Mn(IV) centers. The CP DFT approach was found to provide reasonably acceptable values for D, whereas the CASSCF/NEVPT2 method fared worse, considerably overestimating the magnitude of D in several cases. Both methods were poor in reproducing experimental E/D values. Overall, this work adds to the limited investigations of Mn(IV) ground-state properties and provides an initial assessment for calculating Mn(IV) ZFS parameters with quantum chemical methods. PMID- 27002931 TI - Inherently Chiral Azonia[6]helicene-Modified beta-Cyclodextrin: Synthesis, Characterization, and Chirality Sensing of Underivatized Amino Acids in Water. AB - The (P)- and (M)-3-azonia[6]helicenyl beta-cyclodextrins exhibit L/D selectivities of up to 12.4 and P/M preferences of up to 28.2 upon complexation with underivatized proteinogenic amino acids in aqueous solution at pH 7.3. PMID- 27002930 TI - Maternal and infant outcomes among women vaccinated against pertussis during pregnancy. AB - Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination is recommended for all women during each pregnancy to prevent pertussis in young infants. However, data on the safety of this protective measure are limited and conflicting. To assess maternal and infant outcomes associated with administration of this vaccine during pregnancy, we reviewed medical records of 1,759 women who delivered a singleton infant at a southeast Texas public hospital between November 1, 2012 and June 30, 2014. After excluding women who had inadequate prenatal care or who delivered at <27 weeks gestation, we used multivariable logistic regression analyses to compare 13 outcomes between those who did and did not receive the Tdap vaccine. We examined 6 maternal outcomes (chorioamnionitis, postpartum endometritis, preterm delivery, preterm premature rupture of membranes, induced labor, and mode of delivery) and 7 infant outcomes (low birth weight, very low birth weight, small for gestational age, 5-minute Apgar score, birth defects, and neonatal intensive care unit admission). Maternal Tdap vaccination was associated with decreased odds of cesarean delivery. No associations between maternal Tdap vaccination and infant outcomes were observed. This study demonstrates that Tdap vaccination during pregnancy does not increase the risk of adverse outcomes. PMID- 27002932 TI - Rhodium(III) Catalyzed Carboamination of Alkenes Triggered by C-H Activation of N Phenoxyacetamides under Redox-Neutral Conditions. AB - N-Alkoxyacrylamides are coupled with N-phenoxyacetamides by Rh(III) catalysis through C-H functionalization and amido group transfer under external oxidant free conditions, which affords acyclic alkene carboamination products in an atom economical way. Mechanistic insight into this transformation indicates the amide group in N-alkoxyacrylamide plays a critical role in this C-C/C-N bond formation reaction. This methodology provides a highly efficient way to construct o tyrosine derivatives under mild conditions. PMID- 27002933 TI - The Decremental Protocol as an Alternative Protocol to Measure Maximal Oxygen Consumption in Athletes. AB - PURPOSE: To determine whether a decremental protocol could elicit a higher maximal oxygen consumption (VO2max) than an incremental protocol in trained participants. A secondary aim was to examine whether cardiac-output (Q) and stroke-volume (SV) responses differed between decremental and incremental protocols in this sample. METHODS: Nineteen runners/triathletes were randomized to either the decremental or incremental group. All participants completed an initial incremental VO2max test on a treadmill, followed by a verification phase. The incremental group completed 2 further incremental tests. The decremental group completed a second VO2max test using the decremental protocol, based on their verification phase. The decremental group then completed a final incremental test. During each test, VO2, ventilation, and heart rate were measured, and cardiac variables were estimated with thoracic bioimpedance. Repeated-measures analysis of variance was conducted with an alpha level set at .05. RESULTS: There were no significant main effects for group (P = .37) or interaction (P = .10) over time (P = .45). VO2max was similar between the incremental (57.29 +/- 8.94 mL . kg-1 . min-1) and decremental (60.82 +/- 8.49 mL . kg-1 . min-1) groups over time. Furthermore, Q and SV were similar between the incremental (Q 22.72 +/- 5.85 L/min, SV 119.64 +/- 33.02 mL/beat) and decremental groups (Q 20.36 +/- 4.59 L/min, SV 109.03 +/- 24.27 mL/beat) across all 3 trials. CONCLUSIONS: The findings suggest that the decremental protocol does not elicit higher VO2max than an incremental protocol but may be used as an alternative protocol to measure VO2max in runners and triathletes. PMID- 27002934 TI - Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. AB - BACKGROUND: Rucaparib is an orally available potent selective small-molecule inhibitor of poly(ADP-ribose) polymerase (PARP) 1 and 2. Rucaparib induces synthetic lethality in cancer cells defective in the homologous recombination repair pathway including BRCA-1/2. We investigated the efficacy and safety of single-agent rucaparib in germline (g) BRCA mutation carriers with advanced breast and ovarian cancers. METHODS: Phase II, open-label, multicentre trial of rucaparib in proven BRCA-1/2 mutation carriers with advanced breast and or ovarian cancer, WHO PS 0-1 and normal organ function. Intravenous (i.v.) and subsequently oral rucaparib were assessed, using a range of dosing schedules, to determine the safety, tolerability, dose-limiting toxic effects and pharmacodynamic (PD) and pharmacokinetic (PK) profiles. RESULTS: Rucaparib was well tolerated in patients up to doses of 480 mg per day and is a potent inhibitor of PARP, with sustained inhibition ?24 h after single doses. The i.v. rucaparib (intermittent dosing schedule) resulted in an objective response rate (ORR) of only 2% but with 41% (18 out of 44) patients achieved stable disease for ?12 weeks and 3 patients maintaining disease stabilisation for >52 weeks. The ORR for oral rucaparib (across all six dose levels) was 15%. In the oral cohorts, 81% (22 out of 27) of the patients had ovarian cancer and 12 out of 13, who were dosed continuously, achieved RECIST complete response/partial response (CR/PR) or stable disease (SD) ?12 weeks, with a median duration of response of 179 days (range 84-567 days). CONCLUSIONS: Rucaparib is well tolerated and results in high levels of PARP inhibition in surrogate tissues even at the lowest dose levels. Rucaparib is active in gBRCA-mutant ovarian cancer and this activity correlates with platinum-free interval. The key lessons learned from this study is that continuous rucaparib dosing is required for optimal response, the recommended phase 2 dose (RP2D) for continuous oral scheduling has not been established and requires further exploration and, thirdly, the use of a PD biomarker to evaluate dose-response has its limitations. PMID- 27002936 TI - Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy. AB - BACKGROUND: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect of leaving chronic oral foci of infection untreated on the development of infectious complications in intensively treated haematological patients. METHODS: We included and prospectively evaluated all intensively treated leukaemic patients and patients undergoing ASCT who were referred to our medical centre between September 2012 and May 2014, and who matched the inclusion/exclusion criteria. Acute oral foci of infection were removed before chemotherapy or ASCT, whereas chronic oral foci were left untreated. RESULTS: In total 28 leukaemic and 35 ASCT patients were included. Acute oral foci of infection were found in 2 leukaemic (7%) and 2 ASCT patients (6%), and chronic oral foci of infection in 24 leukaemic (86%) and 22 ASCT patients (63%). Positive blood cultures with microorganisms potentially originating from the oral cavity occurred in 7 patients during treatment, but were uneventful on development of infectious complications. CONCLUSIONS: Our prospective study supports the hypothesis that chronic oral foci of infection can be left untreated as this does not increase infectious complications during intensive chemotherapy. PMID- 27002935 TI - Diagnostic and prognostic role of serum protein peak at 6449 m/z in gastric adenocarcinoma based on mass spectrometry. AB - BACKGROUND: Gastric cancer (GC) is a highly aggressive cancer type associated with significant mortality owing to delayed diagnosis and non-specific symptoms observed in the early stages. Therefore, identification of novel specific GC serum biomarkers for screening purposes is an urgent clinical requirement. METHODS: This study recruited a total of 432 serum samples from 296 GC patients split into the mining and testing sets. We aimed to screen for reliable protein biomarkers from matched serum samples based on mass spectrometry, followed by comparison with three representative conventional markers using receiver operating characteristic and survival curve analyses to ascertain their potential values as diagnostic and prognostic biomarkers for GC. RESULTS: We identified an apoC-III fragment with confirmation in an independent test set from a second hospital. We found that the diagnostic ability of this fragment performed better than current standard GC diagnostic biomarkers both individually and in combination in distinguishing patients with GC from healthy individuals. Moreover, we found that this apoC-III protein fragment represents a more robust potential prognostic factor for GC than the three conventional markers. CONCLUSIONS: In view of these findings, we suggest that apoC-III protein fragment is a novel diagnostic and prognostic biomarker, a complement to conventional biomarkers in detecting GC. PMID- 27002937 TI - Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection. AB - BACKGROUND: Aberrant expression of interleukin-35 (IL-35) has been implicated in dampening antitumour immunity. The aim of this study was to explore the prognostic significance of IL-35 expression in patients with hepatocellular carcinoma (HCC) following curative resection. Furthermore, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy. METHODS: Immunohistochemistry was applied to explore IL-35 expression as well as CD39(+)Foxp3(+) and Foxp3(+) regulatory T cell (Treg) infiltration in tissue microarrays in primary cohort comprising 210 randomly selected HCC patients who underwent curative resection. The results were further verified in an independent validation cohort of 138 HCC patients. RESULTS: Patients with higher expression of IL-35 are more likely to suffer postoperative recurrence. Interleukin-35 was also identified as an independent prognostic factor for recurrence free survival in multivariate analysis. No correlation was detected between IL-35 expression and Foxp3(+) Treg infiltration, whereas significant positive correlation was found between IL-35 expression and CD39(+)Foxp3(+) Treg infiltration. In addition, CD39(+)Foxp3(+) Treg infiltration was also an independent predictor for postoperative recurrence. The nomogram comprising tumour size, tumour vascular invasion, IL-35 and CD39(+)Foxp3(+) Tregs had better predictive accuracy when compared with BCLC stage for RFS. These results were further validated in the validation cohort. CONCLUSIONS: Our data suggest for the first time that IL-35 expression correlates with HCC aggressiveness and emerged as a novel independent prognostic factor for recurrence, thus conferring the rationale to develop a novel therapy of targeting IL-35. Furthermore, IL-35 should be incorporated into nomogram to generate a more accurate predictive model. PMID- 27002939 TI - Loss of the cell polarity determinant human Discs-large is a novel molecular marker of nodal involvement and poor prognosis in endometrial cancer. AB - BACKGROUND: Recent Drosophila studies showed that Discs-large (Dlg) is critical for regulation of cell polarity and tissue architecture. We investigated the possibility that loss of the human homologue of Drosophila Dlg (DLG1) is involved in endometrial carcinogenesis. METHODS: We analysed DLG1 expression in 160 endometrial cancers by immunohistochemical staining. Its expression was confirmed by quantitative real-time PCR (RT-PCR). We investigated the roles of DLG1 in growth and invasion by knockdown experiment in endometrial cancer cell lines. RESULTS: Human DLG1 localises at cellular membrane in normal endometrial tissues. Loss of DLG1 was observed in 37 cases (23.1%). Loss of DLG1 was observed in patients with advanced stage and high-grade histology. It was also observed in patients with nodal metastasis, deep myometrial invasion, and negative oestrogen and progesterone receptors. Patients with loss of DLG1 showed poorer overall survival (P=0.0019). Immunohistochemistry data correlated with RT-PCR data. Knockdown of Dlg1 in endometrial cancer cells resulted in accelerated tumour migration and invasion in vitro. CONCLUSIONS: Tissue polarity disturbance because of loss of DLG1 was shown to confer more aggressive characteristics to endometrial cancer cells. Our study revealed that DLG1 expression is a novel molecular biomarker of nodal metastasis, high-grade histology, and poor prognosis in endometrial cancer. PMID- 27002938 TI - A first in man, dose-finding study of the mTORC1/mTORC2 inhibitor OSI-027 in patients with advanced solid malignancies. AB - BACKGROUND: The kinase activity of mTOR involves 2 multiprotein complexes, (mTORC1-mTORC2). Targeting mTORC1 with rapalogues induces compensatory feedback loops resulting in AKT/ERK activation, which may be abrogated by mTORC2 inhibition. A first-in-human trial evaluating tolerability, pharmacokinetics and pharmacodynamics of the dual TORC1/TORC2 inhibitor OSI-027 was conducted. METHODS: Dose escalation was pursued for three schedules of administration (three consecutive days per week (S1), once a week (S2) and daily dosing (S3)), until dose-limiting toxicities (DLT) were identified. Expansion cohorts with paired tumour biopsies were initiated based on tolerability and pharmacodynamics. RESULTS: One hundred and twenty eight patients with advanced cancer were enrolled. DLT consisted predominantly of fatigue, renal function disturbances and cardiac events. OSI-027 exposure was dose proportional, with Tmax within 4 h and a half-life of ~14 h. Expansion cohorts were initiated for S1 and S2, as MTD for S3 was overall considered suboptimal. Target modulation in peripheral blood mononuclear cells were observed from 30 mg, but in tumour biopsies 120 mg QD were needed, which was a non-tolerable dose due to renal toxicity. No RECIST responses were recorded, with stable disease >6 months in six (5%) patients. CONCLUSIONS: OSI-027 inhibits mTORC1/2 in patients with advanced tumour s in a dose-dependent manner but doses above the tolerable levels in S1 and S3 are required for a sustained biological effect in tumour biopsies. PMID- 27002940 TI - Prognostic role of ERBB2, MET and VEGFA expression in metastatic colorectal cancer patients treated with anti-EGFR antibodies. AB - BACKGROUND: High amplification of epiregulin (EREG) and amphireglin (AREG) in tumour tissues has been previously reported to be associated with better outcome in metastatic colorectal cancer (mCRC) patients who were treated with anti-EGFR antibodies. Here we investigated associations between the expression of other candidate prognostic biomarkers and outcome in mCRC patients receiving similar treatment. METHODS: The relative mRNA levels of seven genes including ERBB2, MET, VEGFA, EREG, AREG, PTEN and ERCC1 between tumour (T) and non-tumour (NT) tissue sections were analysed by quantitative real-time PCR. Relative mRNA values, that is, T/NT ratios, of target genes were calculated and hazard ratios (HRs) for each gene of interest were adjusted for age, gender, performance status, minor RAS mutations and other clinicopathological variables which exhibited P-values<0.1 on the basis of univariate analysis. RESULTS: Among 108 cases who received anti-EGFR antibodies, there were 96 cases of KRAS exon2 wild-type patients enroled in this study. When the cutoff values for relative mRNA levels were set to the upper 25th percentile of all patients, there were statistically significant differences in overall survival (OS) between the patients with high and low levels of EREG (HR: 0.326, 95% CI: 0.136-0.772, P=0.011), ERBB2 (HR: 1.31, 95% CI: 1.084-1.652, P=0.040), MET (HR: 2.48, 95% CI: 1.356-5.463, P=0.026), and VEGF-A (HR: 1.29, 95% CI: 1.036-1.606, P=0.046). In addition, patients with high ERBB2 had shorter progression-free survival (PFS) compared with low ERBB2 (HR: 1.98, 95% CI: 1.062 3.850). There were no significant differences in PFS and OS with respect to relative expression levels of PTEN and ERCC1. The prognostic role of AREG was evaluated in only T sections, as the mRNA expression level of this gene was mostly (91% cases) undetectable in NT sections. Patients with high AREG had longer OS compared with low AREG (HR: 0.227, 95% CI: 0.095-0.808). CONCLUSIONS: Our study has shown that higher T/NT ratios of ERBB2, MET and VEGFA mRNA were associated with worse OS in mCRC patients treated with anti-EGFR antibodies, with higher EREG and AREG were associated with better prognosis in the same setting. These findings will contribute the further understanding and management of anti EGFR antibody treatment in mCRC patients. PMID- 27002942 TI - The Third and Fourth Decades. PMID- 27002941 TI - Factors affecting quality of life in adults with epilepsy in Taiwan: A cross sectional, correlational study. AB - PURPOSE: The purpose of this study was to assess eight factors considered important for quality of life in persons with epilepsy in order to determine which of these components affect quality of life in adults with epilepsy in Taiwan. METHODS: A cross-sectional, correlational study using structured questionnaires assessed 260 patients with epilepsy purposively sampled from a medical center in Northern Taiwan. Health-related quality of life (HRQoL) was evaluated with the Quality of Life in Epilepsy-31 (QOLIE-31) questionnaire. Data also included personal and health-related characteristics, knowledge of epilepsy, efficacy in the self-management of epilepsy, and social support. RESULTS: Scores for the QOLIE-31 were correlated with the following factors: (1) demographic characteristics of age, gender, and income; (2) sleep quality; (3) symptoms of anxiety and depression; (4) epilepsy-specific variables: seizure frequency; types, number, and frequency of antiepileptic drugs (AEDs); and adverse events of AEDs; and (5) social support. Stepwise regression analysis showed that seven factors were predictive for quality of life: anxiety, depression, adverse events of AEDs, social support, seizure frequency of at least once in three months, household income of NT$ 40,001-100,000, and male gender. These factors accounted for 58.2% of the variance of quality of life. SIGNIFICANCE: Our study assessed multiple factors in an examination of relationships and predictive factors for quality of life in adults with epilepsy in Taiwan. Knowledge of these contributing factors can assist health-care providers when evaluating patients with epilepsy to help target interventions for improving quality of life. PMID- 27002943 TI - Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients. AB - BACKGROUND: The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. METHODS AND RESULTS: Thirty-six HF patients (>=60 years) and 40 healthy controls (68 +/- 7 vs 67 +/- 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (beta = -0.34 vs beta = -0.35) were significant predictors of attention, and CCA-BFV (beta = -0.34) was a predictor of executive function. CONCLUSIONS: Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients. PMID- 27002944 TI - Clinical Characteristics, Management, and Outcomes of Hospitalized Heart Failure in a Chinese Population-The Hong Kong Heart Failure Registry. AB - BACKGROUND: Epidemiological data for heart failure (HF) in the Chinese population is scarce. In this study, we described the clinical characteristics and outcomes of new-onset HF in our population. METHODS AND RESULTS: We conducted a retrospective, observational study on consecutive Chinese patients hospitalized for new-onset HF between 2005 and 2012 in our center. A total of 1940 patients (mean age, 78.2 +/- 11.8 years, 54.2% female) were identified. The rate of new HF hospitalization was 0.59 per 1000 population. The most prevalent comorbidities were hypertension (69.8%) and coronary artery disease (29.3%), and 52.3% had HF with preserved ejection fraction (HFpEF). The all-cause mortality was 19.5% at 1 year, 32.1% at 2 years, and 54% at 5 years. Cardiovascular mortality was 7.2% at 1 year, 11.8% at 2 years, and 20.7% at 5 years. No difference in all-cause mortality or cardiovascular mortality was observed between those with HF with reduced ejection fraction than HFpEF. CONCLUSIONS: Our patients with new-onset HF shared similar clinical characteristics with the Caucasian population. The prognosis was poor with high all-cause mortality for both HFpEF and HF with reduced ejection fraction. PMID- 27002945 TI - Reconsidering the benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer. AB - Colorectal cancer is one of the most frequent solid tumors in the western world, with low survival rates in patients with metastatic disease. Doublet chemotherapy regimens such as FOLFOX or FOLFIRI are the mainstay of standard first-line chemotherapy in the metastatic setting. The conventional treatment as a first line approach is continuous application until progression or intolerable toxicities. However, only one third of patients are treated until progression mainly due to the side effects of chemotherapy. Notably, oxaliplatin-containing regimens such as FOLFOX/CapOx or FOLFOXIRI are associated with oxaliplatin induced neuropathy, which is the main reason for treatment discontinuation or treatment de-escalation. On this basis, recent studies have investigated the clinical benefits of bevacizumab-based intermittent and continuous treatment regimens in the metastatic colorectal setting, together with various strategies to optimize maintenance therapy including regimens with targeted therapies, such as cetuximab, ziv-aflibercept and regorafenib. Recent studies have also investigated when maintenance therapy should be initiated as well individualizing treatment based on patient, tumor and treatment characteristics, as well as molecular biomarkers. This article reviews the current evidence for the clinical benefit of intermittent versus continuous treatment in the maintenance treatment setting of metastatic colorectal cancer, and also evaluates the effect of RAS and BRAF mutational status on maintenance strategies. PMID- 27002946 TI - Axillary coverage by whole breast irradiation in 1 to 2 positive sentinel lymph nodes in breast cancer patients. AB - PURPOSE: To evaluate the dosimetric coverage of axillary levels I, II, and III obtained with standard whole breast irradiation in 1 to 2 positive sentinel lymph nodes (SLNs) patients not submitted to axillary lymph nodes dissection (ALND), and to compare the lymph nodes areas coverage obtained with 3D conformal radiation therapy, intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT). METHODS: Patients with 1 to 2 positive SLNs undergoing breast-conserving therapy, without ALND, were included in the analysis. For each patient, 3 treatment plans were performed: a 3D conventional tangential plan, a static IMRT plan, and a volumetric IMRT, designed to encompass the entire breast parenchyma. The volumes of axillary levels I, II, and III receiving 90% and 95% (V90, V95) of the whole breast prescribed dose were evaluated. Dose-volume histograms were compared by means of the Friedman test. RESULTS: Ten patients were enrolled. All defined breast volumes received >95% of the prescribed dose with the 3 techniques. Median V95 for axillary level I was 26.4% (range 4.7%-61.3%) for 3D plans, 8.6% (range 0.64%-19.1%) for static IMRT plans, and 2.6% (range 0.4%-4.7%) for volumetric IMRT plans (p<0.001). Median V95 for axillary level II was 5.4% (range 0%-14.6%), 1.9% (range 0%-15%), and 2.6% (range 0.4%-4.7%) for 3D, static IMRT, and volumetric IMRT, respectively (p<0.001). CONCLUSIONS: Results of our analysis showed that standard 3D tangential whole breast irradiation failed to deliver a therapeutic dose to axillary levels I and II. The coverage was even lower using static and volumetric IMRT techniques. PMID- 27002948 TI - Sequential boost in neoadjuvant irradiation for T3N0-1 rectal cancer: long-term results from a single-center experience. AB - PURPOSE: To evaluate the influence of radiation dose on tumor regression grade (TRG) and sphincter preservation rate in a series of cT3N0-1 rectal cancer patients treated with neoadjuvant chemoradiotherapy (CT-RT) with or without a sequential radiation boost. MATERIALS AND METHODS: Between May 2002 and September 2013, 116 cases were eligible for retrospective evaluation. Radiotherapy was delivered for a total dose of 45 Gy (no boost arm) or 50.4 Gy (boost arm). TRG was evaluated with the Dworak scale. RESULTS: Median follow-up was 62 months (range, 12-138 months). The 5-year overall survival and local control rates were 72% and 93%, respectively. Fifty-five patients (47%) were treated with a sequential radiation boost and 61 (53%) without a boost. Eighty patients (72%) presented T3N0 disease and 32 (28%) T3N1 disease. Concomitant capecitabine was administered in 92 cases (79%) and intravenous 5-fluorouracil in 24 cases (21%). Sphincter preservation was performed in 82% of patients in the boost arm and 66% in the no-boost arm. A higher TRG was related to a longer interval between neoadjuvant treatment and surgery (p<0.001). The probability of a TRG >=2 was 2.5 times higher in the boost arm. A gain in local control, estimated at 4% during the first 3 years after CT-RT, favored the boost arm. CONCLUSIONS: The long-term results from our single-center experience confirm literature data on the role of a sequential boost in tumor response after neoadjuvant CT-RT in a series of cT3N0 1 rectal cancer patients. PMID- 27002947 TI - Combination chemotherapy of solid tumors: an American-Italian collaboration: a celebration of the work of Gianni Bonadonna. AB - This article highlights the important collaboration between the U.S. NCI in Bethesda, Maryland and the Istituto Tumori in Milan, Italy that had a major impact on the development of curative regimens for breast cancer, Hodgkin's disease and diffuse large B cell lymphoma.In addition to his contribution to developing new therapies, Gianni Bonadonna played an important role in bringing highly focused, disciplined, ethical clinical trials to the European continent. PMID- 27002949 TI - Response of extensive breast cancer skin metastases to rechallenge with trastuzumab together with low-dose chemotherapy and insulin. AB - INTRODUCTION: Cutaneous metastasis occurs in about 29% of breast cancer patients and has a deep impact on patient quality of life. METHODS: A 60-year-old woman with cutaneous metastases from heavily pretreated HER2-positive breast cancer received CMFVP (oral cyclophosphamide 100 mg daily; oral prednisone 12.5 mg daily for 2 weeks, then 7.5 mg daily; intravenous weekly methotrexate 25 mg/m2, 5-5 fluorouracil 400 mg/m2 and vincristine 0.5 mg) with weekly trastuzumab and subcutaneous insulin until disease progression. RESULTS: From March 2009 to November 2009 the patient was treated with the described regimen. At the best response, we observed the disappearance of some lesions and cessation of bleeding and thoracic pain. Time to progression was 8 months. CONCLUSIONS: Our patient had clinical benefit from reintroduction of trastuzumab, low-dose chemotherapy and insulin. The explanation of this prolonged response is only speculative and requires further clinical confirmation in the treatment strategy of HER2-positive breast cancer. PMID- 27002950 TI - Transarterial chemoembolization combination therapy vs monotherapy in unresectable hepatocellular carcinoma: a meta-analysis. AB - PURPOSE: To perform a meta-analysis examining the efficacy of transcatheter arterial chemoembolization (TACE) alone or in combination with radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or high-intensity focused ultrasound (HIFU) for unresectable hepatocellular carcinoma (HCC). METHODS: Medline, Embase, the Cochrane Library, and Google Scholar were searched through May 31, 2014, using the following keywords: hepatocellular carcinoma, transarterial chemoembolization, percutaneous ethanol ablation, percutaneous ethanol injection, radiofrequency ablation, and high-intensity focused ultrasound. Randomized controlled trials (RCTs) comparing 1- and 3-year mortality rates in patients with unresectable HCC receiving either TACE alone or TACE in combination with RFA, PEI, or HIFU were included. One- and 3-year survival rates were compared. RESULTS: Eleven RCTs were included. The total number of patients ranged from 37 to 189, mean age ranged from 52 to 73 years, and percentage male ranged from 54% to 94%. Overall, TACE alone was associated with higher 1-year mortality than TACE combination therapies (pooled odds ratio [OR] 2.47, 95% confidence interval [CI] 1.37 to 4.43, p = 0.003). The 1-year mortality rate between TACE alone vs TACE + PEI was not different, but TACE + PEI was associated with a significantly lower 3-year mortality as compared to TACE alone (pooled OR 6.02, 95% CI 3.03 to 11.93, p<0.001). The RFA alone was associated with higher 1 year mortality compared with TACE + RFA (pooled OR 2.20, 95% CI 1.11 to 4.32, p = 0.023). CONCLUSIONS: Transcatheter arterial chemoembolization in combination with percutaneous ablation therapies may improve the survival of patients with unresectable HCC. PMID- 27002951 TI - Risk stratification system and pattern of relapse in patients treated with adjuvant radiotherapy after radical prostatectomy. AB - PURPOSE: To retrospectively evaluate the role of adjuvant radiotherapy (ART) as monotherapy in a cohort of prostate cancer patients with undetectable prostate specific antigen (PSA) after surgery and to propose a risk stratification system. METHODS: Between 2003 and 2010, 174 consecutive patients were treated with ART (median dose 71 Gy) at a single institution. Subsequently, we assigned a score of 1 to the following risk factors (RF): T stage >=3b, presurgical PSA >=10 ng/mL, pathologic Gleason score (GS) >=4 + 3, and positive surgical margin (R1). The scores were then summed to stratify the population into low risk (LR), intermediate risk (IR), and high risk (HR). RESULTS: Median follow-up was 61 months (range 4-105). Five-year biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), and overall survival (OS) were respectively 93%, 97.1%, and 98.6%. On univariate analyses, GS was the only variable related to bRFS (p = 0.04) and to cRFS (p = 0.05). Any variable was related to OS. Kaplan-Meier analysis showed that HR patients (3-4 RF) had a worse bRFS (p = 0.02) compared to LR patients (0 RF or R1 as single RF); IR patients (1 2 RF) had a lower bRFS compared to LR patients (p = 0.06). Patients with R1 as single RF have the same bRFS as patients with 0 RF (p = 0.6) and are considered as LR patients. CONCLUSIONS: Adjuvant radiotherapy leads to excellent bRFS and cRFS rates at 5 years (93.3% and 97.1%, respectively) in our population. Patients with multiple RF are at higher risk of bRFS. Patients with R1 as single RF have bRFS rates comparable to patients without any RF. PMID- 27002952 TI - Leukocytoclastic vasculitis associated with hairy cell leukemia at diagnosis: a case report and review of the literature. AB - BACKGROUND: Autoimmune manifestations may occur in patients with hairy cell leukemia (HCL), and some rare cases of polyarteritis nodosa and leukocytoclastic vasculitis have been reported. However, data regarding the treatment of these cutaneous manifestations are lacking, given the rarity of the concomitance of HCL and vasculitic syndromes. CASE PRESENTATION: We present a 37-year-old man with paraneoplastic leukocytoclastic vasculitis complicating newly diagnosed HCL. The vasculitis completely resolved after the first 3 weekly administrations of cladribine, which is regarded as the gold-standard treatment for this disease. The underlying leukemia showed refractoriness to the same agent, thus requiring a second line of treatment. CONCLUSIONS: The clinical picture we have observed is of interest for the following reasons: i) it confirms an existing pathogenetic relationship between this lymphoproliferative disorder and its cutaneous manifestations, as suggested by the prompt resolution of the purpuric lesions upon cladribine administration; ii) it indicates that cladribine is an effective treatment for HCL-related paraneoplastic syndromes, including leukocytoclastic vasculitis; iii) the evolution and the outcomes of the paraneoplastic manifestations may be independent of those of the underlying leukemia, which showed less than a partial response to its initial treatment. PMID- 27002953 TI - The evaluation of clopidogrel use in perioperative general surgery patients: a prospective randomized controlled trial. AB - BACKGROUND: The perioperative safety profile of clopidogrel, a potent antiplatelet agent used in the management of cardiovascular disease, is unknown, and there are no evidence-based guidelines recommending for either its interruption or continuation at this time. The aim of this study was to determine whether patients who are maintained on clopidogrel before general surgical procedures are at increased risk of perioperative bleeding complications. METHODS: Patients receiving clopidogrel at the time of elective general surgery were randomized to either discontinue clopidogrel 1 week before surgery (group A) or continue clopidogrel into surgery (group B). All other antiplatelet and anticoagulant agents were discontinued before surgery. The primary end points were perioperative bleeding requiring intraoperative or postoperative transfusion of blood or blood components and bleeding-related readmission, reoperation, or mortality within 90 days of surgery. The secondary end points were perioperative myocardial infarction or cerebrovascular accidents within 90 days of surgery. RESULTS: Thirty-nine patients were enrolled and underwent 43 general surgical operations. Twenty-one procedures were randomized to group A and 22 to group B. The most commonly performed individual procedures were open inguinal hernia repair (23%), laparoscopic cholecystectomy (21%), open ventral hernia repair (15%), laparoscopic ventral hernia repair (11%), and laparoscopic inguinal hernia repair (9%). No perioperative mortalities, bleeding events requiring blood transfusion, or reoperations occurred. One readmission for intra-abdominal hematoma requiring percutaneous drainage occurred in each group (group A: 4.8% vs group B: 4.5%; P = 1.0). No myocardial infarctions or cerebrovascular accidents were observed or reported. CONCLUSIONS: The outcomes from this prospective study suggest that, patients undergoing commonly performed elective general surgical procedures can be safely maintained on clopidogrel without increased perioperative bleeding risk. PMID- 27002954 TI - Recurrence in patients with clinically early-stage papillary thyroid carcinoma according to tumor size and surgical extent. AB - BACKGROUND: To investigate whether post-treatment recurrence differs by tumor size or surgical extent in clinically early-stage papillary thyroid carcinoma (PTC) patients. METHODS: A total of 1,041 surgical patients with PTC 4 cm or less and no clinical evidence of metastases to regional or distant sites were included. Cox proportional hazard models were used to identify the clinicopathological variables predictive of post-treatment recurrence. RESULTS: Central nodal involvement was found in 313 (34.1%) of 918 patients who underwent prophylactic central lymph node dissection. For the median follow-up of 83 months, 25 (2.4%) of 1,041 patients had a regional recurrence and 12 (1.2%) patients died of other causes. Male gender, tumor size, extranodal extension, and positive resection margin remained independent variables predictive of recurrence by multivariate analysis (P < .05 each). There was no significant impact of age (<45 vs >=45 years, P = .944) or surgical extent (unilateral vs bilateral thyroidectomy, P = .776) on recurrence. CONCLUSIONS: Tumor size in patients with PTC of 4 cm or less is an important predictive factor for post-treatment recurrence. PMID- 27002955 TI - The routine use of prosthetic mesh in austere environments: dogma vs data. AB - BACKGROUND: Mesh repair has become the standard in adult hernia repairs. Mesh infection is an uncommon but potentially devastating complication. Currently, there is widespread dogma against the use of prosthetic mesh (PM) in deployed or austere environments but little available data to support or refute this bias. METHODS: Retrospective review of all hernia repairs over 1 year in a forward deployed surgical unit in Afghanistan. Demographics, hernia type, repair performed, and mesh type were evaluated. Follow-up was completed up to 6 weeks and then as needed for up to a year, and complications to include infection were recorded. RESULTS: Sixty-six patients were identified, mean age was 38 (range 3 to 80) and 98% were male. Single-dose perioperative antibiotics and standard sterile technique were used in all cases. The majority (70%) had PM placed. The mean operative time was 54 min, and mean estimated blood loss was less than 25 cm(3). The vast majority of our hernias were inguinal (95%) with 1 ventral and 2 umbilical hernias. In the PM group, there were no surgical site infections, no mesh infections, and no mesh explantation or reoperation. There were no recurrences in either group identified at up to 1-year postoperation. There was no statistically significant difference in any outcome measure between the PM and no-PM groups. CONCLUSIONS: The use of PM for hernia repairs in the austere or forward environment appears safe and did not increase the risk of wound infection, mesh infections, or recurrence. PMID- 27002956 TI - Content Analysis and User Characteristics of a Smartphone-Based Online Support Group for People Living with HIV. AB - BACKGROUND: Although there is growing interest in mobile applications and online support groups to enhance chronic disease self-management, little is known about their potential impact for people living with HIV (PLWH). INTRODUCTION: We developed an innovative online support group delivered through a community message board (CMB) within a clinic-affiliated smartphone application Positive Links (PL). We analyzed characteristics of posters and nonposters to the CMB and evaluated content posted to the CMB. MATERIALS AND METHODS: For this study, 38 HIV-infected patients received cell phones with the PL application that included the opportunity to interact with other users on a CMB. Logistic regressions investigated associations between participant characteristics and posting. CMB messages were downloaded and analyzed qualitatively. RESULTS: 24 participants posted to the CMB; 14 did not. Participants had lower odds of posting if they were white (p = 0.028) and had private insurance (p = 0.003). Participants had higher odds of posting if they had unsuppressed viral loads (p = 0.034). Of the 840 CMB messages over 8 months, 62% had psychosocial content, followed by community chat (29%), and biomedical content (10%). DISCUSSION: Psychosocial content was most prevalent on this CMB, in contrast to other online forums dominated by informational content. Participants who posted expressed support for each other, appreciation for the community, and a perception that the app played a positive role in their HIV self-management. CONCLUSIONS: This CMB on a clinic affiliated mobile application may reach vulnerable populations, including racial/ethnic minorities and those of lower socioeconomic status, and provide psychosocial support to PLWH. PMID- 27002958 TI - Nanozymes: an emerging field bridging nanotechnology and biology. PMID- 27002959 TI - Eye contact affects attention more than arousal as revealed by prospective time estimation. AB - Eye contact can both increase arousal and engage attention. Because these two changes impact time estimation differently, we were able to use a prospective time estimation task to assess the relative changes in arousal and attention during eye contact. Pairs of participants made a 1-minute prospective time estimate while sitting side-by-side and performing three different gaze trials: looking at the wall away from their partner (baseline/away trials), looking at their partner's profile (profile trials), or making eye contact with their partner (eye contact trials). We found that participants produced significantly longer estimates when they were engaged in eye contact, more so than when they looked at another person's profile or baseline. As research has shown that people produce shorter estimates during arousing events and longer estimates when attention is captured, we attribute this difference to the attention-demanding process of interacting with another person, via mutual eye contact, over and above any changes in arousal. PMID- 27002960 TI - Auditory spatial localization: Developmental delay in children with visual impairments. AB - For individuals with visual impairments, auditory spatial localization is one of the most important features to navigate in the environment. Many works suggest that blind adults show similar or even enhanced performance for localization of auditory cues compared to sighted adults (Collignon, Voss, Lassonde, & Lepore, 2009). To date, the investigation of auditory spatial localization in children with visual impairments has provided contrasting results. Here we report, for the first time, that contrary to visually impaired adults, children with low vision or total blindness show a significant impairment in the localization of static sounds. These results suggest that simple auditory spatial tasks are compromised in children, and that this capacity recovers over time. PMID- 27002961 TI - Lentibacillus kimchii sp. nov., an extremely halophilic bacterium isolated from kimchi, a Korean fermented vegetable. AB - A Gram-positive, aerobic, non-motile and extremely halophilic bacterial strain, designated K9(T), was isolated from kimchi, a Korean fermented food. The strain was observed as endospore-forming rod-shaped cells showing oxidase and catalase activity. It was found to grow at 10.0-30.0 % (w/v) NaCl (optimum, 15.0-20.0 %), pH 7.0-8.0 (optimum, pH 7.5) and 15-40 degrees C (optimum, 30 degrees C). The polar lipids of strain K9(T) were identified as phosphatidylglycerol, three unidentified phospholipids and an unidentified glycolipid. The isoprenoid quinone was identified as menaquinone-7. The major cellular fatty acids (>20 % of the total) were found to be anteisio-C15:0 and anteisio-C17:0. The cell wall peptidoglycan composition was determined to contain meso-diaminopimelic acid. The G + C content of genomic DNA was determined to be 48.2 mol %. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the isolated strain is closely related to Lentibacillus salinarum AHS-1(T) (96.7 % sequence similarity). Based on its phenotypic, chemotaxonomic and phylogenetic data, strain K9(T) is considered to represent a novel species of the genus Lentibacillus, for which the name Lentibacillus kimchii sp. nov., is proposed. The type strain is K9(T) (=KACC 18490(T) = JCM 30234(T)). PMID- 27002962 TI - Abundances, diversity and seasonality of (non-extremophilic) Archaea in Alpine freshwaters. AB - The objectives of this study were to assess abundances and community compositions of Archaea within a heterogeneous set of freshwater systems in the Austrian Alps. Seasonal changes and geographical differences within Archaea, considering abiotic and biotic factors (e.g. temperature, pH, total organic carbon (TOC), NH4 (+), bacteria, fungi), were analysed in this context. Water samples were collected from 8 lakes, 10 creeks and the river Inn in 2014. Qualitative-quantitative data were derived via a comprehensive set of (quantitative) PCR assays and PCR-DGGE (denaturing gradient gel electrophoresis) based methodology, which was evaluated concerning specificity and reliability either previously or in this study. QPCR derived archaeal abundances reached values of 10(3) copies mL(-1) on average, with a peak in winter-spring ('Cold Peak'), and covered 0-15 % (average: 1 %) of the microbial populations. This peak correlated with significantly raised TOC and low NH4 (+) levels during the cold seasons. Stagnant waters showed significantly higher archaeal abundances and diversities than flowing ones. Among methanogens, Methanosarcinales were the most common order. PCR-DGGE data showed that the archaeal communities were site-specific and could function as an ecological marker, in contrast to the more heterogeneous and unsteady bacterial and fungal community. This is attributable to the highly heterogeneous community of methanogenic Archaea (MA, Euryarchaeota), while only two species, Nitrosopumilus maritimus and Ca. Nitrososphaera gargensis, were found to be the ubiquitous representatives of ammonia-oxidizing Archaea (AOA, Thaumarchaeota) in Alpine freshwaters. This work emphasises the diversity, distribution and seasonality of non-extremophilic Archaea in Alpine freshwaters, with a first insight into their ecophysiological potential. PMID- 27002963 TI - Editorial: Cell biology in agriculture and food sciences. PMID- 27002964 TI - Morpho-histodifferentiation of Billbergia Thunb. (Bromeliaceae) nodular cultures. AB - Nodule cultures are formed through an intermediate morphogenetic route that lies between organogenesis and somatic embryogenesis. Although well described in many species, different aspects of the morphological and histological development of nodules remain to be clarified. Based on their threatened status and high ornamental value, Billbergia alfonsi-joannis and Billbergia zebrina, two epiphytic bromeliad species endemic to the South American Atlantic Forest, were studied. Nodular cultures were induced to grow from nodal segments taken from etiolated seedlings grown in vitro for 12 weeks in the dark on MS medium supplemented with 1 MUM TDZ. Samples were taken for analysis weekly over 8 weeks of growth and analyzed under light, transmission electron, and scanning electron microscopes. Morphological and histological analysis showed that nodular clusters originated from stem pericycles and consisted of a polycenter, cambial tissue, cortical parenchyma, and a covering tissue. The polycenter consisted of an organizational center dispersed in parenchymal tissue. Each organizational center was formed by a vascular system surrounded by a bundle sheath. A cambial tissue surrounded these polycenters, promoting the regeneration of new nodules and leading to the formation of buds and roots. Primary nodules could generate secondary nodules in a repetitive process. Thus, histological analysis revealed the origin and formation of nodular cultures. These new data will support the establishment of micropropagation protocols and regeneration on a large scale for these species. PMID- 27002965 TI - In silico study on Arabidopsis BAG gene expression in response to environmental stresses. AB - BAG (Bcl-2 athanogene) family proteins are conserved in a wide range of eukaryotes, and they have been proposed to play a crucial role in plant programmed cell death (PCD). During the past decade, with the help of advanced bioinformatics tools, seven homologs of BAG genes have been identified in the Arabidopsis genome; these genes are involved in pathogen attack and abiotic stress conditions. In this study, gene expression of Arabidopsis BAG family members under environmental stresses was analyzed using the Botany Array Resource (BAR) expression browser tool and the in silico data were partially confirmed by qRT-PCR analysis for the selected stress- and hormone-treated conditions related to environmental stresses. Particularly, the induction of AtBAG6 gene in response to heat shock was confirmed by using GUS reporter lines. The loss of the AtBAG6 gene resulted into impairment in basal thermotolerance of plant and showed enhanced cell death in response to heat stress. To elucidate the regulatory mechanisms of BAG genes, we analyzed ~1-kbp promoter regions for the presence of stress-responsive elements. Our transcription profiling finally revealed that the Arabidopsis BAG genes differentially respond to environmental stresses under the control of specifically organized upstream regulatory elements. PMID- 27002966 TI - Recent developments in ex vivo platelet production. AB - The platelet is a component of blood that functions to initiate blood clotting. Abnormal platelet count and function can lead to a life-threatening condition caused by excessive bleeding. At present, platelet supply for transfusion can be obtained only from platelet donation. However, platelets cannot be stored for longer than 7 days, meaning that routine isolation is required to maintain platelet supply for transfusion. To mitigate for potential platelet shortages, several strategies have been proposed to generate platelets ex vivo. By employing both of natural and artificial approaches, several researchers have successfully generated biomaterials with characteristics similar to human-derived platelets. Their reports indicated that the biomaterials could mimic the aggregation of human-isolated platelets, further suggesting the possibility to substitute or complement human-isolated platelets. The current review summarizes the progress in ex vivo platelet production and gives a prospect for the possible approaches to achieving a feasible platelet factory, based on the Good Manufacturing Practice standards. PMID- 27002967 TI - Erratum to: Post-herpetic Neuralgia: a Review. PMID- 27002968 TI - Is frailty a prognostic factor for critically ill elderly patients? AB - AIM: The study aimed to investigate the effects of frailty on clinical outcomes of patients in an intensive care unit (ICU). METHODS: In this prospective study, 122 patients (59 frail, 37 pre-frail and 26 robust) were included. A frailty index (FI) derived from comprehensive geriatric assessment parameters was used for the evaluation. The FI score of <=0.25 was considered as robust, 0.25-0.40 as pre-frail and >0.40 as frail. The prognostic effects of FI were investigated and FI and APACHE II and SOFA scores, the prognostic scores using in ICU, were compared. RESULTS: Median age of the patients was 71 years old and 50.8 % were male. ICU mortality rate and median length of stay (LOS) were 51.6 % and 8 days (min-max: 1-148), respectively. ICU mortality was higher (69.2, 56.8 and 40.7 %, respectively, p = 0.040) and median overall survival was lower in frail group compared to pre-frail and robust subjects (23, 31 and 140 days, p = 0.013, respectively). Long term mortality over 3 and 6 months in frail patients were 80.8 and 84.6 %, respectively and significantly higher than others. Multivariate analysis showed that LOS in ICU (HR 1.067, 95 % CI 1.021-1.114), SOFA score (HR 1.272, 95 % CI 1.096-1.476) and FI (HR 39.019, 95 % CI 1.235-1232.537) were the independent correlates for ICU mortality (p = 0.004, p = 0.002 and 0.038, respectively). There was a weak but statistically significant positive correlation between APACHE II and FI scores (r = 0.190, p = 0.036). CONCLUSIONS: FI may be used as a predictor for the evaluation of elderly patients' clinical outcomes in ICUs. PMID- 27002969 TI - Keeping Quiet Just Wouldn't be Right: Children's and Adolescents' Evaluations of Challenges to Peer Relational and Physical Aggression. AB - Youth peer groups hold many different types of norms, including norms supporting aggressive behavior. Challenging or standing up to such aggressive norms can be difficult for children and adolescents, given the pressures to conform to groups. In the current study, the relationship between individual judgments and expectations of the judgments of a peer group about the acceptability of challenging aggressive group norms was investigated. The sample included 9-10 and 13-14 year-olds (N = 292, 52.4 % female). Participants evaluated groups with norms condoning physical and relational aggression. Participants were more supportive of challenges to relational aggression than challenges to physical aggression. Additionally, age-related differences were found, with younger children perceiving challenges to group norms as more feasible than did adolescents. Participants individually rated challenging aggressive norms as okay, but thought that groups would be much less supportive of such challenges. The results also documented the influence of gender stereotypes about aggressive behavior on children's and adolescents' evaluations. PMID- 27002970 TI - Plant pressure sensitive adhesives: similar chemical properties in distantly related plant lineages. AB - MAIN CONCLUSION: A mixture of resins based on aliphatic esters and carboxylic acids occurs in distantly related genera Peperomia and Roridula , serving different functions as adhesion in seed dispersal and prey capture. According to mechanical characteristics, adhesive secretions on both leaves of the carnivorous flypaper Roridula gorgonias and epizoochorous fruits of Peperomia polystachya were expected to be similar. The chemical analysis of these adhesives turned out to be challenging because of the limited available mass for analysis. Size exclusion chromatography and Fourier transform infrared spectroscopy were suitable methods for the identification of a mixture of compounds, most appropriately containing natural resins based on aliphatic esters and carboxylic acids. The IR spectra of the Peperomia and Roridula adhesive resemble each other; they correspond to that of a synthetic ethylene-vinyl acetate copolymer, but slightly differ from that of natural tree resins. Thus, the pressure sensitive adhesive properties of the plant adhesives are chemically proved. Such adhesives seem to appear independently in distantly related plant lineages, habitats, life forms, as well as plant organs, and serve different functions such as prey capture in Roridula and fruit dispersal in Peperomia. However, more detailed chemical analyses still remain challenging because of the small available volume of plant adhesive. PMID- 27002971 TI - Gr and hp-1 tomato mutants unveil unprecedented interactions between arbuscular mycorrhizal symbiosis and fruit ripening. AB - MAIN CONCLUSION: Systemic responses to an arbuscular mycorrhizal fungus reveal opposite phenological patterns in two tomato ripening mutants depending whether ethylene or light reception is involved. The availability of tomato ripening mutants has revealed many aspects of the genetics behind fleshy fruit ripening, plant hormones and light signal reception. Since previous analyses revealed that arbuscular mycorrhizal symbiosis influences tomato berry ripening, we wanted to test the hypothesis that an interplay might occur between root symbiosis and fruit ripening. With this aim, we screened seven tomato mutants affected in the ripening process for their responsiveness to the arbuscular mycorrhizal fungus Funneliformis mosseae. Following their phenological responses we selected two mutants for a deeper analysis: Green ripe (Gr), deficient in fruit ethylene perception and high-pigment-1 (hp-1), displaying enhanced light signal perception throughout the plant. We investigated the putative interactions between ripening processes, mycorrhizal establishment and systemic effects using biochemical and gene expression tools. Our experiments showed that both mutants, notwithstanding a normal mycorrhizal phenotype at root level, exhibit altered arbuscule functionality. Furthermore, in contrast to wild type, mycorrhization did not lead to a higher phosphate concentration in berries of both mutants. These results suggest that the mutations considered interfere with arbuscular mycorrhiza inducing systemic changes in plant phenology and fruits metabolism. We hypothesize a cross talk mechanism between AM and ripening processes that involves genes related to ethylene and light signaling. PMID- 27002973 TI - Revisiting the iron pools in cucumber roots: identification and localization. AB - MAIN CONCLUSION: Fe deficiency responses in Strategy I causes a shift from the formation of partially removable hydrous ferric oxide on the root surface to the accumulation of Fe-citrate in the xylem. Iron may accumulate in various chemical forms during its uptake and assimilation in roots. The permanent and transient Fe microenvironments formed during these processes in cucumber which takes up Fe in a reduction based process (Strategy I) have been investigated. The identification of Fe microenvironments was carried out with (57)Fe Mossbauer spectroscopy and immunoblotting, whereas reductive washing and high-resolution microscopy was applied for the localization. In plants supplied with (57)Fe(III)-citrate, a transient presence of Fe-carboxylates in removable forms and the accumulation of partly removable, amorphous hydrous ferric oxide/hydroxyde have been identified in the apoplast and on the root surface, respectively. The latter may at least partly be the consequence of bacterial activity at the root surface. Ferritin accumulation did not occur at optimal Fe supply. Under Fe deficiency, highly soluble ferrous hexaaqua complex is transiently formed along with the accumulation of Fe-carboxylates, likely Fe-citrate. As (57)Fe-citrate is non removable from the root samples of Fe deficient plants, the major site of accumulation is suggested to be the root xylem. Reductive washing results in another ferrous microenvironment remaining in the root apoplast, the Fe(II) bipyridyl complex, which accounts for ~30 % of the total Fe content of the root samples treated for 10 min and rinsed with CaSO4 solution. When (57)Fe(III)-EDTA or (57)Fe(III)-EDDHA was applied as Fe-source higher soluble ferrous Fe accumulation was accompanied by a lower total Fe content, confirming that chelates are more efficient in maintaining soluble Fe in the medium while less stable natural complexes as Fe-citrate may perform better in Fe accumulation. PMID- 27002972 TI - Renaissance in phytomedicines: promising implications of NGS technologies. AB - MAIN CONCLUSION: Medicinal plant research is growing significantly in faith to discover new and more biologically compatible phytomedicines. Deposition of huge genome/trancriptome sequence data assisted by NGS technologies has revealed the new possibilities for producing upgraded bioactive molecules in medicinal plants. Growing interest of investors and consumers in the herbal drugs raises the need for extensive research to open the facts and details of every inch of life canvas of medicinal plants to produce improved quality of phytomedicines. As in agriculture crops, knowledge emergence from medicinal plant's genome/transcriptome, can be used to assure their amended quality and these improved varieties are then transported to the fields for cultivation. Genome studies generate huge sequence data which can be exploited further for obtaining information regarding genes/gene clusters involved in biosynthesis as well as regulation. This can be achieved rapidly at a very large scale with NGS platforms. Identification of new RNA molecules has become possible, which can lead to the discovery of novel compounds. Sequence information can be combined with advanced phytochemical and bioinformatics tools to discover functional herbal drugs. Qualitative and quantitative analysis of small RNA species put a light on the regulatory aspect of biosynthetic pathways for phytomedicines. Inter or intra genomic as well as transcriptomic interactive processes for biosynthetic pathways can be elucidated in depth. Quality management of herbal material will also become rapid and high throughput. Enrichment of sequence information will be used to engineer the plants to get more efficient phytopharmaceuticals. The present review comprises of role of NGS technologies to boost genomic studies of pharmaceutically important plants and further, applications of sequence information aiming to produce enriched phytomedicines. Emerging knowledge from the medicinal plants genome/transcriptome can give birth to deep understanding of the processes responsible for biosynthesis of medicinally important compounds. PMID- 27002975 TI - No Habitat Selection during Spring Migration at a Meso-Scale Range across Mosaic Landscapes: A Case Study with the Woodcock (Scolopax rusticola). AB - Success of migration in birds in part depends on habitat selection. Overall, it is still poorly known whether there is habitat selection amongst landbird migrants moving across landscapes. Europe is chiefly covered by agro-forestry mosaic landscapes, so migratory species associated to either agricultural landscapes or woodland habitats should theoretically find suitable stopover sites along migration. During migration from wintering to breeding quarters, woodcocks (Scolopax rusticola) tagged with PTT satellite-tracking transmitters were used to test for the hypothesis that migrants associated to agro-forest habitats have no habitat selection during migration, at a meso-scale level. Using a GIS platform we extracted at a meso-scale range habitat cover at stopover localities. Results obtained from comparisons of soil covers between points randomly selected and true stopover localities sites revealed, as expected, the species may not select for particular habitats at a meso-scale range, because the habitat (or habitats) required by the species can be found virtually everywhere on their migration route. However, those birds stopping over in places richer in cropland or mosaic habitats including both cropland and forest and with proportionally less closed forest stayed for longer than in areas with lower surfaces of cropland and mosaic and more closed forest. This suggests that areas rich in cropland or mosaic habitat were optimal. PMID- 27002974 TI - Exogenous nitric oxide improves sugarcane growth and photosynthesis under water deficit. AB - MAIN CONCLUSION: Nitric oxide (NO)-mediated redox signaling plays a role in alleviating the negative impact of water stress in sugarcane plants by improving root growth and photosynthesis. Drought is an environmental limitation affecting sugarcane growth and yield. The redox-active molecule nitric oxide (NO) is known to modulate plant responses to stressful conditions. NO may react with glutathione (GSH) to form S-nitrosoglutathione (GSNO), which is considered the main reservoir of NO in cells. Here, we investigate the role of NO in alleviating the effects of water deficit on growth and photosynthesis of sugarcane plants. Well-hydrated plants were compared to plants under drought and sprayed with mock (water) or GSNO at concentrations ranging from 10 to 1000 MUM. Leaf GSNO sprayed plants showed significant improvement of relative water content and leaf and root dry matter under drought compared to mock-sprayed plants. Additionally, plants sprayed with GSNO (>= 100 MUM) showed higher leaf gas exchange and photochemical activity as compared to mock-sprayed plants under water deficit and after rehydration. Surprisingly, a raise in the total S-nitrosothiols content was observed in leaves sprayed with GSH or GSNO, suggesting a long-term role of NO mediated responses to water deficit. Experiments with leaf discs fumigated with NO gas also suggested a role of NO in drought tolerance of sugarcane plants. Overall, our data indicate that the NO-mediated redox signaling plays a role in alleviating the negative effects of water stress in sugarcane plants by protecting the photosynthetic apparatus and improving shoot and root growth. PMID- 27002976 TI - D-Alanine-Controlled Transient Intestinal Mono-Colonization with Non-Laboratory Adapted Commensal E. coli Strain HS. AB - Soon after birth the mammalian gut microbiota forms a permanent and collectively highly resilient consortium. There is currently no robust method for re-deriving an already microbially colonized individual again-germ-free. We previously developed the in vivo growth-incompetent E. coli K-12 strain HA107 that is auxotrophic for the peptidoglycan components D-alanine (D-Ala) and meso diaminopimelic acid (Dap) and can be used to transiently associate germ-free animals with live bacteria, without permanent loss of germ-free status. Here we describe the translation of this experimental model from the laboratory-adapted E. coli K-12 prototype to the better gut-adapted commensal strain E. coli HS. In this genetic background it was necessary to complete the D-Ala auxotrophy phenotype by additional knockout of the hypothetical third alanine racemase metC. Cells of the resulting fully auxotrophic strain assembled a peptidoglycan cell wall of normal composition, as long as provided with D-Ala and Dap in the medium, but could not proliferate a single time after D-Ala/Dap removal. Yet, unsupplemented bacteria remained active and were able to complete their cell cycle with fully sustained motility until immediately before autolytic death. Also in vivo, the transiently colonizing bacteria retained their ability to stimulate a live-bacteria-specific intestinal Immunoglobulin (Ig)A response. Full D-Ala auxotrophy enabled rapid recovery to again-germ-free status. E. coli HS has emerged from human studies and genomic analyses as a paradigm of benign intestinal commensal E. coli strains. Its reversibly colonizing derivative may provide a versatile research tool for mucosal bacterial conditioning or compound delivery without permanent colonization. PMID- 27002977 TI - The Impact of WHO Essential Medicines Policies on Inappropriate Use of Antibiotics. AB - BACKGROUND: Inappropriate overuse of antibiotics contributes to antimicrobial resistance (AMR), yet policy implementation to reduce inappropriate antibiotic use is poor in low and middle-income countries. AIMS: To determine whether public sector inappropriate antibiotic use is lower in countries reporting implementation of selected essential medicines policies. MATERIALS AND METHODS: Results from independently conducted antibiotic use surveys in countries that did, and did not report implementation of policies to reduce inappropriate antibiotic prescribing, were compared. Survey data on four validated indicators of inappropriate antibiotic use and 16 self-reported policy implementation variables from WHO databases were extracted. The average difference for indicators between countries reporting versus not reporting implementation of specific policies was calculated. For 16 selected policies we regressed the four antibiotic use variables on the numbers of policies the countries reported implementing. RESULTS: Data were available for 55 countries. Of 16 policies studied, four (having a national Ministry of Health unit on promoting rational use of medicines, a national drug information centre and provincial and hospital drugs and therapeutics committees) were associated with statistically significant reductions in antibiotic use of >=20% in upper respiratory infection (URTI). A national strategy to contain antibiotic resistance was associated with a 30% reduction in use of antibiotics in acute diarrheal illness. Policies seemed to be associated with greater effects in antibiotic use for URTI and diarrhea compared with antibiotic use in all patients. There were negative correlations between the numbers of policies reported implemented and the percentage of acute diarrhoea cases treated with antibiotics (r = -0.484, p = 0.007) and the percentage of URTI cases treated with antibiotics (r = -0.472, p = 0.005). Major study limitations were the reliance on self-reported policy implementation data and antibiotic use data from linited surveys. CONCLUSIONS: Selected essential medicines policies were associated with lower antibiotic use in low and middle income countries. PMID- 27002978 TI - Closed reduction for arytenoid dislocation under local anesthesia. AB - CONCLUSION: Closed reduction under local anesthesia continues to be an effective and well-tolerated method for treating arytenoid dislocation. Bilateral arytenoid dislocation is an uncommon occurrence, and the principles of management are the same as for unilateral dislocation. OBJECTIVES: To evaluate the treatment outcomes of closed reduction for arytenoid dislocation under local anesthesia and to conduct an exhaustive review of the literature on bilateral arytenoid dislocation. METHODS: Thirty-three patients with arytenoid dislocation were treated with closed reduction under local anesthesia. Arytenoid motion, GRBAS (grade, roughness, breathiness, asthenia, strain), maximum phonation time (MPT), self-assessed Voice Handicap Index (VHI), and acoustic voice analysis were used to evaluate the clinical outcomes. RESULTS: Following closed reduction, 33 patients were divided into a 'satisfied' group (n = 26) and a 'dissatisfied' group (n = 7). In the 'satisfied' group, G, R, B, A, MPT, VHI, jitter%, shimmer%, normalized noise energy (NNE), and noise-to-harmonic ratio (NHR) were significantly improved compared with measurements taken before closed reduction (p < 0.05). The results for F0 and S score were not significantly different. In the 'dissatisfied' group, VHI, MPT, F0, and shimmer% were not significantly different 1 month after reduction. However, statistically significant change was observed in jitter% and NHR. PMID- 27002980 TI - Species-Specific Effects of Ant Inhabitants on Bromeliad Nutrition. AB - Predator activities may lead to the accumulation of nutrients in specific areas of terrestrial habitats where they dispose of prey carcasses. In their feeding sites, predators may increase nutrient availability in the soil and favor plant nutrition and growth. However, the translocation of nutrients from one habitat to another may depend on predator identity and diet, as well as on the amount of prey intake. Here we used isotopic (15N) and physiological methods in greenhouse experiments to evaluate the effects of the identity of predatory ants (i.e., the consumption of prey and nest sites) on the nutrition and growth of the bromeliad Quesnelia arvensis. We showed that predatory ants with protein-based nutrition (i.e., Odontomachus hastatus, Gnamptogenys moelleri) improved the performance of their host bromeliads (i.e., increased foliar N, production of soluble proteins and growth). On the other hand, the contribution of Camponotus crassus for the nutritional status of bromeliads did not differ from bromeliads without ants, possibly because this ant does not have arthropod prey as a preferred food source. Our results show, for the first time, that predatory ants can translocate nutrients from one habitat to another within forests, accumulating nutrients in their feeding sites that become available to bromeliads. Additionally, we highlight that ant contribution to plant nutrition may depend on predator identity and its dietary requirements. Nest debris may be especially important for epiphytic and terrestrial bromeliads in nutrient-poor environments. PMID- 27002979 TI - Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma. AB - BACKGROUND: Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. METHODS: We conducted a population-based birth cohort study of mother child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. RESULTS: Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose dependent manner. Compared with vaginal delivery, C-section delivery increased odds of childhood asthma by 34% (OR 1.34, 95%CI 1.29, 1.39) in the univariate analysis and 11% after adjusting for other environmental exposures and covariates (AOR 1.11, 95%CI 1.06, 1.15). Maternal GBS was associated with a significant increased risk of childhood asthma in the univariate analysis (OR 1.27, 95%CI 1.19, 1.35), but not in the adjusted analysis (AOR 1.03, 95%CI 0.96, 1.10). In the subgroup analysis of children whose maternal antibiotic use information was available, maternal antibiotic use was associated with an increased risk of childhood asthma in a similar dose-dependent manner in the univariate and adjusted analyses (OR 1.13, 95%CI 1.12, 1.15; AOR 1.06, 95%CI 1.05, 1.08 for every additional course). Compared with infants with the lowest number of exposures (no UTI during pregnancy, vaginal delivery, at least five older siblings at home, no antibiotics during infancy), infants with the highest number of exposures (at least three UTIs during pregnancy, C-section delivery, no older siblings, eight or more courses of antibiotics during infancy) had a 7.77 fold increased odds of developing asthma (AOR: 7.77, 95%CI: 6.25, 9.65). Lastly, infant antibiotic use had the greatest impact on asthma risk compared with maternal UTI during pregnancy, mode of delivery and having older siblings at home. CONCLUSION: Early-life exposures, maternal UTI during pregnancy (maternal antibiotic use), mode of delivery, infant antibiotic use, and having older siblings at home, are associated with an increased risk of childhood asthma in a cumulative manner, and for those continuous variables, a dose-dependent relationship. Compared with in utero exposures, exposures occurring during infancy have a greater impact on the risk of developing childhood asthma. PMID- 27002982 TI - Cholinesterase Inhibitor Donepezil Increases Mitochondrial Biogenesis through AMP Activated Protein Kinase in the Hippocampus. AB - OBJECTIVE: Donepezil, a widely prescribed drug for Alzheimer's disease (AD), is now considered to have multimodal actions beyond cholinesterase inhibition. We aimed to see whether donepezil enhances mitochondrial biogenesis and relevant signaling pathways since mitochondrial dysfunction is a key feature of the hypometabolic AD brain. METHODS: As a metabolic gauge, AMP-activated protein kinase (AMPK) was investigated as a tentative mediator of neurometabolic action of donepezil. Changes in phospho-AMPK levels, mitochondrial biogenesis, and ATP levels were measured upon donepezil treatment using neuroblastoma cells, primary cultured neurons and ex vivo hippocampal tissue of adult mice. RESULTS: Donepezil dose-dependently increased mitochondrial biogenesis and ATP levels as well as expression of PGC-1alpha and NRF-1 in neuroblastoma cells. Donepezil dose dependently activated AMPK; however, inhibition of AMPK abolished the observed effects of donepezil, indicating that AMPK is a key mediator of donepezil's action. Notably, mitochondrial biogenesis upon donepezil treatment was mainly observed within dendritic regions of primary cultured hippocampal neurons. Levels of synaptic markers were also increased by donepezil. Finally, AMPK- dependent mitochondrial biogenesis by donepezil was confirmed in organotypic hippocampal tissue. CONCLUSIONS: Our findings indicate that AMPK/PGC-1alpha signaling is involved in beneficial actions of donepezil on neurometabolism. Pharmacological activation of AMPK might be a promising approach to counteract AD pathogenesis associated with brain hypometabolism. PMID- 27002981 TI - Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn's disease and ulcerative colitis. AB - OBJECTIVE: The infliximab biosimilar CT-P13 (Remsima((r)), Inflectra((r))) was approved in Europe for the treatment of inflammatory bowel disease (IBD) based on extrapolation of data from patients with rheumatic disease. Because there are limited published reports on clinical outcomes for IBD patients treated with CT P13, we monitored responses to induction treatment with this biosimilar in patients with Crohn's disease (CD) or ulcerative colitis (UC) in centres across the Czech Republic. MATERIAL AND METHODS: Fifty-two patients with CD (n = 30) or UC (n = 22) were treated with 5 mg/kg CT-P13 for up to 14 weeks. Effectiveness of therapy was evaluated with the Crohn's Disease Activity Index (CDAI) or the Mayo Scoring System (MSS) in patients with CD or UC, respectively, before and after 14 weeks. Additional goals were to evaluate weight changes, serum C-reactive protein (CRP) levels, and complications/adverse events. RESULTS: In patients with CD, remission (CDAI <150) was achieved in 50.0% of cases, and partial response (>=70 point decrease in CDAI score from baseline) in the remaining 50.0%. In patients with UC, remission (total score on partial Mayo index <=2 points) was achieved in 40.9% of cases, partial response (>=2-point decrease in partial Mayo score from baseline) in 54.5%, and no response in 4.5%. There were statistically significant improvements in CDAI, MSS and CRP serum levels after 14 weeks of therapy, and body weight increased. Four adverse events were identified (n = 1 each): lower extremity phlebothrombosis, herpes labialis, pneumonia and allergic reaction. CONCLUSIONS: This prospective observational study provides evidence of the effectiveness of CT-P13 in IBD. PMID- 27002983 TI - New time-saving predictor algorithm for multiple breath washout in adolescents. AB - BACKGROUND: Multiple breath washout (MBW) is an informative but time-consuming test. This study evaluates the uncertainty of a time-saving predictor algorithm in adolescents. METHODS: Adolescents were recruited from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) birth cohort. MBW trials were performed at 13 y of age with Innocor model Inn00400 using sulfur hexafluoride (SF6) as tracer gas. Measurements were analyzed using a mixed model focusing on two prediction points doubling (t5%) and quadrupling (t10%) the standard end point (t2.5%). RESULTS: One hundred and seventy-two MBW trials conducted in 78 adolescents with and without asthma from COPSAC2000 were included. At t10%, the washout time (WoT) was reduced by 41%, and an uncertainty of 0.159 lung clearance index (LCI) units was introduced (+/-2 SD), +/-1.27). At t5%, the WoT was reduced by 25%, with an uncertainty of 0.083 LCI units (+/ 0.558). The optimal prediction point, which led to most saved time and least uncertainty was t5%. CONCLUSION: The predictor algorithm is capable of shortening the MBW test time but introduces an increasing uncertainty with earlier prediction points. This first-of-a-kind prediction algorithm holds promise in shortening the MBW test in children but should be used with caution in subjects with normal LCI values. PMID- 27002984 TI - Clinical associations with immature breathing in preterm infants: part 2-periodic breathing. AB - BACKGROUND: Periodic breathing (PB) is a normal immature breathing pattern in neonates that, if extreme, may be associated with pathologic conditions. METHODS: We used our automated PB detection system to analyze all bedside monitor chest impedance data on all infants <35 wk' gestation in the University of Virginia Neonatal Intensive Care Unit from 2009-2014 (n = 1,211). Percent time spent in PB was calculated hourly (>50 infant-years' data). Extreme PB was identified as a 12 h period with PB >6 SDs above the mean for gestational age (GA) and postmenstrual age and >10% time in PB. RESULTS: PB increased with GA, with the highest amount in infants 30-33 wk' GA at about 2 wk' chronologic age. Extreme PB was identified in 76 infants and in 45% was temporally associated with clinical events including infection or necrotizing enterocolitis (NEC), immunizations, or caffeine discontinuation. In 8 out of 28 cases of septicemia and 10 out of 21 cases of NEC, there was a >2-fold increase in %PB over baseline on the day prior to diagnosis. CONCLUSION: Infants <35 wk GA spend, on average, <6% of the time in PB. An acute increase in PB may reflect illness or physiological stressors or may occur without any apparent clinical event. PMID- 27002985 TI - ROBO2 gene variants in children with primary nonsyndromic vesicoureteral reflux with or without renal hypoplasia/dysplasia. AB - BACKGROUND: Primary nonsyndromic vesicoureteral reflux (VUR) and VUR with renal hypoplasia/dysplasia (VUR-RHD) are common congenital anomalies of the kidney and urinary tract (CAKUT). Sequence variations of the ROBO2 gene were investigated in children with nonsyndromic VUR or VUR-RHD. METHODS: Single-strand conformation polymorphism (SSCP) electrophoresis or multiple restriction fragment SSCP (MRF SSCP), followed occasionally by direct sequencing, was used to screen 103 patients and 200 controls for nucleotide changes. Gene polymorphisms and transposable elements were investigated using bioinformatics. RESULTS: Two single nucleotide polymorphisms were detected: IVS1-53 and IVS5-31. The frequency of A allele of IVS1-53G>A did not differ significantly between patients and controls. IVS1-53 does not affect mRNA splicing according to in silico analysis. IVS5-31A>G substitution was found in one patient, reported here for the first time in VUR. In silico results demonstrated alteration in two serine/arginine-rich (SR) protein-binding sites and two additional acceptor sites. The ROBO2 gene sequence was found to contain 25.9% transposable elements. CONCLUSION: ROBO2 variants were not found to be associated with nonsyndromic VUR or VUR-RHD, providing further evidence for genetic heterogeneity. The role of transposable elements in ROBO2 gene expression in CAKUT needs further investigation since they are generally considered to be mutagens. PMID- 27002986 TI - Preparation and characterization of PLGA-beta-CD polymeric nanoparticles containing methotrexate and evaluation of their effects on T47D cell line. AB - Among all cancers that affect women, breast cancer has most mortality rate. It is essential to attain more safe and efficient anticancer drugs. Recent advances in medical nanotechnology and biotechnology have caused in novel improvements in breast and other cancer drug delivery. Methotrexate is an anticancer drug that prevents the dihydrofolate reductase enzyme, which inhibits in the formation of DNA, RNA and proteins which have poor water-solubility. For enhancing the solubility and stability of drugs in delivery systems, we used methotrexate loaded PLGA- beta-cyclodextrin nanoparticles. The PLGA- beta-cyclodextrin nanoparticles were synthesized by a double emulsion method and characterized with FT-IR and SEM. T47D breast cancer cell lines were treated with equal concentrations of methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles and free methotrexate. MTT assay confirmed that methotrexate-loaded PLGA- beta cyclodextrin nanoparticles enhanced cytotoxicity and drug delivery in T47D breast cancer cells. These results indicate that encapsulated drugs could be effective in controlled drug release for a sustained period would serve the purpose for long-term treatment of many diseases such as breast cancer. PMID- 27002987 TI - CodHonEditor: Spreadsheets for Codon Optimization and Editing of Protein Coding Sequences. AB - Gene synthesis is getting more important with the growing availability of low cost commercial services. The coding sequences are often "optimized" as for the relative synonymous codon usage (RSCU) before synthesis, which is generally included in the commercial services. However, the codon optimization processes are different among different providers and are often hidden from the users. Here, the d'Hondt method, which is widely adopted as a method for determining the number of seats for each party in proportional-representation public elections, is applied to RSCU fitting. This allowed me to make a set of electronic spreadsheets for manual design of protein coding sequences for expression in Escherichia coli, with which users can see the process of codon optimization and can manually edit the codons after the automatic optimization. The spreadsheets may also be useful for molecular biology education. PMID- 27002988 TI - The functional capacity and quality of life of women with advanced breast cancer. AB - BACKGROUND: The rehabilitation needs of patients with metastatic breast cancer (MBC) are poorly studied. The primary aim of the study was to evaluate the functional capacity of women with MBC and quality of life (QoL). METHODS: The present study is an open, non-randomized, prospective cross-sectional observation study. The functional capacity of 128 MBC patients with ongoing cancer treatments, were studied in Helsinki University Hospital (HUS): Peak expiratory flow (PEF), dynamic and static balance, 6 minute walking distance (6MWD), 10 meter walking, sit-to-stand test, repeated squat, grip strength, shoulder movement, pain, and QoL by Beck's depression scale (BDI), health assessment questionnaire (HAQ), RAND SF-36 and EORTC QLQ-30 items. RESULTS: The walking capacity was compromised in half and the strength of the lower extremities in one third of the patients. PEF was below the normal reference in 55 %, static balance in 62 % and dynamic balance in 73 % (<=60 year olds) and 81 % (>=61 year olds). The grip power was lowered in 44/30 % of the patients (right/left) and the shoulder movement was restricted in 30 %. Some disability in physical functioning experienced 55 % (HAQ) and 37 % felt depressive (BDI). The QoL (RAND SF-36) was poor especially in the field of physical, role and social functioning and bodily pain (<0.001). Pain, depression, and a poor 6MWD results independently determined the physical component of QoL (p < 0.001). CONCLUSIONS: The functional capacity of patients with MBC was significantly lowered. This, in association with distressing symptoms like pain and depression causes a vicious circle further leading to functional disabilities and impaired QoL. PMID- 27002989 TI - Computed Tomography and Magnetic Resonance Imaging of the Thyroid and Parathyroid Glands. AB - Computed tomography (CT) and magnetic resonance imaging (MRI) are advanced imaging modalities that are not typically utilized as part of the initial evaluation of thyroid and parathyroid pathology. However, both modalities have applications in complex cases, particularly in the reoperative setting and in operative planning for initial or recurrent carcinomas. As part of a multimodal approach, CT and MRI can increase the successful preoperative localization of abnormal parathyroid glands. Newer imaging modalities, such as PET-CT and SPECT CT in thyroid imaging, and 4D-CT in parathyroid imaging, can provide information on the anatomy as well as the function of pathologic tissues. Both modalities provide excellent assessment of the extent of disease, local invasion and distant metastases. Drawbacks include cost and availability, and these should be weighed against benefits in the context of the management of thyroid and parathyroid disease. PMID- 27002990 TI - Ethical Challenges for the Medical Expert Witness. PMID- 27002991 TI - Managing Care of an Intrapartum Patient with Agitation and Psychosis: Ethical and Legal Implications. PMID- 27002992 TI - Expedited Partner Therapy: Clinical Considerations and Public Health Explorations. PMID- 27002993 TI - How Should Clinicians Treat Patients Who Might Be Undocumented? PMID- 27002994 TI - One Model of Collaborative Learning for Medical and Law Students at the University of Baltimore and Johns Hopkins University. PMID- 27002995 TI - Enabling Individualized Criminal Sentencing While Reducing Subjectivity: A Tablet Based Assessment of Recidivism Risk. PMID- 27002996 TI - Needle Exchange Programs' Status in US Politics. PMID- 27002997 TI - Graduate Medical Education Specialty Mix and Geographic Residency Program Maldistribution: Is There a Role for the ACGME? AB - As we've stated, GME is the final common pathway toward clinical medical practice in the US. It makes sense, then, that national physician workforce policy aimed at meeting future public health demands should be directed at this phase of medical education. It would also make sense that ACGME, as the single accreditor of all residency programs in the US, should be engaged in physician workforce policymaking on behalf of the public. We identified three issues that must be addressed in order for the ACGME to assume this role: First, there must be a national agreed-upon and long-term plan for the design and implementation of the health care delivery system. Second, there must be a nationally coordinated strategy for identifying long-term physician workforce needs and funding mechanisms to physician and other health care professional developments. Third, in order to execute these roles, the ACGME must receive support from the profession and national and state-level statutory protection from enforcement of state and federal antitrust law. PMID- 27002998 TI - Shedding Privacy Along With our Genetic Material: What Constitutes Adequate Legal Protection against Surreptitious Genetic Testing? PMID- 27002999 TI - State Oversight of Hospital Consolidation: Inadequate to Protect Patients' Rights and Community Access to Care. PMID- 27003000 TI - Privacy Protection in Billing and Health Insurance Communications. PMID- 27003001 TI - Federal Privacy Protections: Ethical Foundations, Sources of Confusion in Clinical Medicine, and Controversies in Biomedical Research. PMID- 27003002 TI - Medical Malpractice Reform--Historical Approaches, Alternative Models, and Communication and Resolution Programs. PMID- 27003003 TI - Undocumented Immigrants Face a Unique Set of Risks from Tuberculosis Treatment: Is This Just? PMID- 27003005 TI - Correction: Integrated and Total HIV-1 DNA Predict Ex Vivo Viral Outgrowth. PMID- 27003004 TI - Nanoparticles for intravascular applications: physicochemical characterization and cytotoxicity testing. AB - AIM: We report the physicochemical analysis of nanosystems intended for cardiovascular applications and their toxicological characterization in static and dynamic cell culture conditions. METHODS: Size, polydispersity and zeta potential were determined in 10 nanoparticle systems including liposomes, lipid nanoparticles, polymeric and iron oxide nanoparticles. Nanoparticle effects on primary human endothelial cell viability were monitored using real-time cell analysis and live-cell microscopy in static conditions, and in a flow model of arterial bifurcations. RESULTS & CONCLUSIONS: The majority of tested nanosystems were well tolerated by endothelial cells up to the concentration of 100 MUg/ml in static, and up to 400 MUg/ml in dynamic conditions. Pilot experiments in a pig model showed that intravenous administration of liposomal nanoparticles did not evoke the hypersensitivity reaction. These findings are of importance for future clinical use of nanosystems intended for intravascular applications. PMID- 27003009 TI - Stricter pathogen limits imminent for poultry. PMID- 27003010 TI - Implications of small intestinal thickening in cats. PMID- 27003006 TI - Assessment of In Vivo Antidiabetic Properties of Umbelliferone and Lupeol Constituents of Banana (Musa sp. var. Nanjangud Rasa Bale) Flower in Hyperglycaemic Rodent Model. AB - Banana is an extensively cultivated plant worldwide, mainly for its fruit, while its ancillary product, the banana flower is consumed as a vegetable and is highly recommended for diabetics in the traditional Indian medicine system. This study is based on an investigation of the in vivo antihyperglycaemic activity of Umbelliferone (C1) and Lupeol (C2) isolated from the ethanol extract of banana flower (EF) in alloxan induced diabetic rat model. Diabetic rats which were administered with C1, C2 and EF (100 and 200 mg/kg b. wt.) for 4 weeks showed deterioration in fasting hyperglycaemia and reversal of abnormalities in serum/urine protein, urea and creatinine, when compared to the diabetic control group of rats. The diabetic group of rats fed with EF, C1 and C2 (100 mg/kg b. wt.) once daily, for a period of 28 days resulted in a significant reduction of diabetic symptoms viz., polyphagia, polydipsia, polyuria and urine sugar together with an improved body weight. HbA1c extent was reduced whereas levels of insulin and Hb were increased. Both the extract and compounds wielded positive impacts in diabetic rats by reversal of altered activities of hepatic marker enzymes viz., aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP); glycolytic enzyme (hexokinase); shunt enzyme (glucose-6-phosphate dehydrogenase); gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6 bisphosphatase, lactate dehydrogenase) and pyruvate kinase. The characteristic diabetic complications such as hypercholesterolemia and hypertriacylglycerolemia also significantly reverted to normal in the serum/liver of diabetic rats. Besides these, the treatment increased the activities of enzymatic and non enzymatic antioxidants in the serum and liver. The histological observations revealed a marked regeneration of the beta-cells in the drug treated diabetic rats. In conclusion, the present study illustrates that EF, C1 and C2 enhances the glycolytic activities, besides increasing the hepatic glucose utilization in diabetic rats by stimulating insulin secretion from the remnant beta-cells along with potential enzymatic and non-enzymatic antioxidant activities. PMID- 27003012 TI - New Veterinary Biologic Products. PMID- 27003011 TI - Preparing veterinary students for entry-level practice by identifying new graduate outcomes. PMID- 27003013 TI - What Is Your Diagnosis? Embryonal subclass of juvenile rhabdomyosarcoma. PMID- 27003014 TI - What Is Your Diagnosis? Herniation of the left caudal lung lobe through the left seventh intercostal space. PMID- 27003015 TI - ECG of the Month. PMID- 27003016 TI - Anesthesia Case of the Month. PMID- 27003017 TI - Correction: Compendium of Animal Rabies Prevention and Control, 2016. PMID- 27003018 TI - Pathology in Practice. Poorly productive, osteoblastic osteosarcoma of the left paranasal sinuses in a 1-year-old colt. PMID- 27003019 TI - Rabies surveillance in the United States during 2014. PMID- 27003020 TI - Comparison of refractometry and biuret assay for measurement of total protein concentration in canine abdominal and pleural fluid specimens. AB - OBJECTIVE: To compare total protein (TP) concentrations in canine pleural and abdominal fluid specimens as measured by refractometry and biuret assay. DESIGN: Diagnostic test evaluation. SAMPLE: Data regarding 92 pleural and 148 abdominal fluid specimens from dogs with various diseases. PROCEDURES: TP concentrations in fluid specimens as measured by refractometry and biuret assay were recorded. Strength of association between sets of measurements was assessed by Spearman rank correlations and Bland-Altman plots. Optimal concentration cutoff for diagnostic discrimination between exudate and nonexudate was identified by construction of receiver operating characteristic curves. RESULTS: Median TP concentration in pleural fluid specimens was 2.7 g/dL (range, 0.3 to 4.8 g/dL) for refractometry and 2.9 g/dL (range, 0.7 to 5.8 g/dL) for biuret assay. Median TP concentration in abdominal fluid specimens was 3.5 g/dL (range, 0.1 to 6.0 g/dL) for refractometry and 3.5 g/dL (range, 0.6 to 5.7 g/dL) for biuret assay. Correlation was significant between refractometric and biuret results for pleural (rho = 0.921) and abdominal (rho = 0.908) fluid. Bland-Altman plots revealed bias of -0.18 g/dL for pleural fluid and -0.03 g/dL for abdominal fluid for refractometry versus biuret assay. With a TP concentration of >= 3 g/dL used to distinguish exudate from nonexudate, sensitivity of refractometry was 77% for pleural fluid and 80% for abdominal fluid. Specificity was 100% and 94%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Refractometry yielded acceptable results for measurement of TP concentration in canine pleural and abdominal fluid specimens, providing a more rapid and convenient method than biuret assay. PMID- 27003021 TI - Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits. AB - OBJECTIVE: To determine the clinical effectiveness and safety of a compounded sustained-release formulation of buprenorphine, compared with effects of regular buprenorphine, for postoperative analgesia in rabbits. DESIGN: Blinded randomized controlled clinical trial. ANIMALS: 24 purpose-bred adult male New Zealand White rabbits. PROCEDURES: Rabbits received titanium implants in each tibia as part of another study. Immediately prior to surgery, each rabbit received regular buprenorphine hydrochloride (0.02 mg/kg [0.009 mg/lb], SC, q 12 h for 3 days) or 1 dose of a compounded sustained-release formulation of buprenorphine (0.12 mg/kg [0.055 mg/lb], SC) followed by an equal volume of saline (0.9% NaCl) solution (SC, q 12 h for 3 days) after surgery. For 7 days after surgery, rabbits were evaluated for signs of pain by means of rabbit grimace and activity scoring and for adverse effects. RESULTS: No significant differences were identified between treatment groups in grimace and activity scores at any point. No major adverse effects were detected for either drug. However, 3 rabbits that received regular buprenorphine had pain scores suggestive of moderate to severe pain by the time dose administration was due (ie, within the 12-hour administration interval). No clinically important differences were detected in intraoperative anesthetic or postoperative recovery variables. CONCLUSIONS AND CLINICAL RELEVANCE: Sustained release buprenorphine administered SC at 0.12 mg/kg was at least as effective as regular buprenorphine in providing analgesia for rabbits following orthopedic surgery without any major adverse effects. This sustained-release formulation represents an important alternative for rabbit analgesia with potential to improve rabbit welfare over existing analgesic standards. PMID- 27003022 TI - Hepatocutaneous syndrome in Shih Tzus: 31 cases (1996-2014). AB - OBJECTIVE: To characterize findings in Shih Tzus with progressive superficial necrolytic dermatitis and degenerative vacuolar hepatopathy consistent with hepatocutaneous syndrome. DESIGN: Retrospective case series. ANIMALS: 31 Shih Tzus. PROCEDURES: Medical records were reviewed to obtain information on signalment, history, treatment, outcome, and results of clinicopathologic testing, abdominal ultrasonography, and histologic examination of skin and liver specimens. A pedigree analysis was performed. RESULTS: There were 16 males and 15 females. Median age at the time of diagnosis was 8 years (range, 5 to 14 years). Common clinical signs included lethargy, inappetence, weight loss, and lameness. Twenty-five dogs had cutaneous lesions consistent with hepatocutaneous syndrome; the remaining 6 initially only had hepatic abnormalities, but 3 of the 6 subsequently developed cutaneous lesions. Common clinicopathologic abnormalities included microcytosis (15/24 [63%] dogs) and high serum alkaline phosphatase activity (24/24 [100%] dogs). Hepatic ultrasonographic findings included a hyperechoic or heteroechoic appearance to the parenchyma with innumerable hypoechoic nodules. Histologic hepatic lesions consisted of degenerative vacuolar (glycogen and lipid) hepatopathy associated with minimally fibrotic to nonfibrotic, noninflammatory, proliferative nodules. Pedigree analysis confirmed a common ancestry in 12 of 18 dogs. Median survival time was 3 months (range, 1 to 36 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that HCS may have a heritable component in Shih Tzus, although the condition may also be identified in Shih Tzus without affected relatives. Clinical, clinicopathologic, ultrasonographic, and histologic abnormalities in affected Shih Tzus were similar to those previously reported for dogs of other breeds with HCS. PMID- 27003023 TI - Evaluation of baseline cortisol concentration to monitor efficacy of twice-daily administration of trilostane to dogs with pituitary-dependent hyperadrenocorticism: 22 cases (2008-2012). AB - OBJECTIVE: To evaluate use of cortisol concentration prior to ACTH stimulation (baseline) to monitor efficacy of twice-daily administration of trilostane to dogs with pituitary-dependent hyperadrenocorticism (PDH). DESIGN: Retrospective case series. ANIMALS: 22 dogs with PDH. PROCEDURES: The database of a veterinary hospital was searched to identify dogs with PDH that were treated with the FDA approved veterinary formulation of trilostane twice daily between January 1, 2008, and December 31, 2012. For each dog, signalment and details regarding each hospital visit including comorbidities, electrolyte concentrations, and clinical signs were extracted from the record. For each ACTH stimulation test performed, the respective correlations between baseline cortisol concentration and the cortisol concentration after ACTH stimulation (ACTH-stimulated cortisol concentration) and resultant decision regarding trilostane dose adjustment were determined. Excessive suppression of cortisol production was defined as an ACTH stimulated cortisol concentration < 2.0 MUg/dL. The ability of various baseline cortisol concentrations to predict whether a dog had excessive suppression of cortisol production was determined. RESULTS: 109 ACTH stimulation tests were performed for the 22 dogs. A baseline cortisol concentration > 3.2 MUg/dL predicted that ACTH-stimulated cortisol concentration would be >= 2.0 MUg/dL with 100% certainty; however, 14 of 64 tests with a baseline cortisol concentration > 3.2 MUg/dL had an ACTH-stimulated cortisol concentration <= 3.2 MUg/dL, which was suggestive of inadequate adrenocortical cortisol reserves. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that baseline cortisol concentration should not be used as the sole monitoring tool for management of dogs with PDH treated with trilostane twice daily. PMID- 27003024 TI - Vaginal fold prolapse in a dog with pyometra and ovarian papillary cystadenocarcinoma. AB - CASE DESCRIPTION: A 7-year-old 42-kg (92.4-lb) sexually intact nulliparous female Italian Mastiff was examined because of a history of vaginal prolapse during diestrus. CLINICAL FINDINGS: A physical examination revealed vaginal fold prolapse. Abdominal ultrasonography revealed an enlarged uterus with hypoechogenic content, corpora lutea in the ovaries, and a cyst in the right ovary. Hematologic abnormalities included leukocytosis, neutrophilia, mild anemia, and low Hct. Progesterone and estradiol concentrations were 9.36 ng/mL and 30.42 pg/mL, respectively, in serum and 72.72 ng/mL and 792 pg/mL, respectively, in the ovarian cystic fluid. TREATMENT AND OUTCOME: Ovariohysterectomy was performed; the prolapsed tissue was repositioned by external manipulation and maintained in situ by temporary apposition of the vulvar lips with a retention suture. Anatomic and histologic examinations of the excised tissues revealed pyometra and papillary cystadenocarcinoma in the right ovary. The vaginal hyperplasia completely regressed at 35 days after surgery; 5 months after surgery, the dog's general condition was considered good. CLINICAL RELEVANCE: Findings in this case were indicative of a hormonally active ovarian papillary cystadenocarcinoma in a female dog in diestrus. Hormone production by the cystadenocarcinoma was the predisposing factor that induced pyometra, mucosal hyperplasia, and vaginal fold prolapse in the dog. On the basis of these concurrent disorders, ovariohysterectomy was an appropriate treatment. PMID- 27003025 TI - Identification of Heterobilharzia americana infection in a dog residing in Indiana with no history of travel. AB - CASE DESCRIPTION: A 1-year-old castrated male dog residing in Indiana was examined because of intermittent vomiting of 4 months' duration. CLINICAL FINDINGS: The dog's condition did not resolve with medication. Diagnostic imaging revealed a possible partial obstruction at the ileocecal junction. An exploratory laparotomy was performed. The jejunum contained diffusely distributed, nodular, intramural lesions; 2 biopsy specimens were collected from representative lesions. The pancreas was grossly swollen, and pancreatitis was presumed present. No other abnormalities were observed in the abdomen. Histologic examination of the submitted biopsy specimens revealed infection with Heterobilharzia americana. TREATMENT AND OUTCOME: After diagnosis, the dog was treated with fenbendazole suspension (48 mg/kg [21.8 mg/lb], PO, q 24 h) for 10 days. This treatment was subsequently repeated 11 and 80 days later. One week after the end of the last fenbendazole treatment, several H americana eggs were detected in a fecal sample via saline sedimentation, and the dog was given praziquantel (25 mg/kg [11.4 mg/lb], PO, q 8 h) for 2 days. No gastrointestinal signs were evident 4 months after that treatment. CLINICAL RELEVANCE: The dog described in this report was the first autochthonous canine case of H americana infection in Indiana, to the authors' knowledge; this case has confirmed that the distribution of this parasite in the Midwestern United States is broader than previously known. Increased awareness of the distribution of H americana should aid veterinarians in early, noninvasive diagnosis and appropriate treatment of affected animals. Repeated treatments and recheck fecal examinations may be necessary when managing these cases. PMID- 27003026 TI - SLUG expression is an indicator of tumour recurrence in high-grade endometrial carcinomas. AB - AIMS: To investigate how SNAIL and SLUG were involved in the nature of high-grade endometrial carcinomas (grade 3 endometrioid carcinoma, serous carcinoma and clear cell carcinoma), we analysed the correlation of their expression status with clinicopathological characteristics and evaluated their prognostic significance. METHODS AND RESULTS: We performed immunohistochemical staining in 52 high-grade endometrial carcinomas. Expression status of SNAIL and SLUG was classified into a high expression (positive in more than 50% of the tumour cells) and a low expression. Thirteen cases (25%) showed a high expression of SLUG, whereas all 52 cases showed a low expression of SNAIL. High expression of SLUG was correlated significantly with tumour recurrence (P = 0.0203) and aberrant p53 expression (P = 0.000559). Overall survival was worse in patients with high SLUG expression at all stages (P = 0.0327) and in those who underwent adjuvant therapy (P = 0.00963). Among the patients with complete tumour resection, high SLUG expression was associated with worse recurrence-free survival (RFS) in the patients at all stages (P = 0.00264), at stages III/IV (P = 0.0146), and who underwent adjuvant therapy (P = 0.000743). SLUG expression was identified as an independent factor of RFS by multivariate analysis (hazard ratio 5.938, 95% confidence interval 1.251-28.18, P = 0.025). CONCLUSIONS: SLUG expression could be correlated with TP53 mutational status and could be involved in therapeutic resistance resulting in tumour recurrence. A high expression level of SLUG can be an indicator of recurrence and a therapeutic target for long-term remission in high-grade endometrial carcinomas. PMID- 27003028 TI - Comparison of Femoral Head Rotation and Varus Collapse Between a Single Lag Screw and Integrated Dual Screw Intertrochanteric Hip Fracture Fixation Device Using a Cadaveric Hemi-Pelvis Biomechanical Model. AB - OBJECTIVE: This study compared the stabilizing effect of 2 intertrochanteric (IT) fracture fixation devices in a cadaveric hemi-pelvis biomechanical model. METHODS: Eleven pairs of cadaveric osteopenic female hemi-pelves with intact hip joint and capsular ligaments were used. An unstable IT fracture (OTA 31-A2) was created in each specimen and stabilized with a single lag screw device (Gamma 3) or an integrated dual screw (IDS) device (InterTAN). The hemi-pelves were inverted, coupled to a biaxial apparatus and subjected to 13.5 k cycles of loading (3 months) using controlled, oscillating pelvic rotation (0-90 degrees) plus cyclic axial femoral loading at a 2:1 body weight (BW) ratio. Femoral head rotation and varus collapse were monitored optoelectonically. For specimens surviving 3 months of loading, additional loading was performed in 0.25 * BW/250 cycle increments to a maximum of 4 * BW or failure. RESULTS: Femoral head rotation with IDS fixation was significantly less than the single lag screw construct after 3 months of simulated loading (P = 0.016). Maximum femoral head rotation at the end of 4 * BW loading was 7* less for the IDS construct (P = 0.006). Varus collapse was significantly less with the IDS construct over the entire loading cycle (P = 0.021). CONCLUSIONS: In this worst-case model of an osteopenic, unstable, IT fracture, the IDS construct, likely owing to its larger surface area, noncylindrical profile, and fracture compression, provided significantly greater stability and resistance to femoral head rotation and varus collapse. PMID- 27003027 TI - Role of metabolic modulator Bet-CA in altering mitochondrial hyperpolarization to suppress cancer associated angiogenesis and metastasis. AB - Solid tumors characteristically reflect a metabolic switching from glucose oxidation to glycolysis that plays a fundamental role in angiogenesis and metastasis to facilitate aggressive tumor outcomes. Hyperpolarized mitochondrial membrane potential is a manifestation of malignant cells that compromise the intrinsic pathways of apoptosis and confer a suitable niche to promote the cancer associated hallmark traits. We have previously reported that co-drug Bet-CA selectively targets cancer cells by inducing metabolic catastrophe without a manifest in toxicity. Here we report that the same molecule at a relatively lower concentration deregulates the cardinal phenotypes associated with angiogenesis and metastasis. In mice syngeneic 4T1 breast cancer model, Bet-CA exhibited effective abrogation of angiogenesis and concomitantly obliterated lung metastasis consistent with altered mitochondrial bioenergetics. Furthermore, Bet CA significantly lowered vascular endothelial growth factor (VEGF) levels and obviated matrix metalloproteases (MMP-2/9) production directly to the criterion where abrogation of autocrine VEGF/VEGFR2 signalling loop was documented. In vitro studies anticipatedly documented the role of Bet-CA in inhibiting actin remodeling, lamellipodia formation and cell membrane ruffling to constitutively suppress cell motility and invasion. Results comprehensively postulate that Bet CA, a mitochondria targeting metabolic modulator may serve as an excellent candidate for combating angiogenesis and metastasis. PMID- 27003029 TI - Periprosthetic Atypical Femoral Fractures in Patients on Long-term Bisphosphonates: A Multicenter Retrospective Review. AB - OBJECTIVES: To define the characteristics of periprosthetic atypical femoral fractures (PAFFs) in patients on long-term bisphosphonate treatment and to provide a guide to the diagnosis and long-term treatment of these patients based on the literature. DESIGN: Multicenter retrospective review. SETTING: Fifteen orthopaedic centers in the United States and Canada, including members of the Canadian Orthopaedic Trauma Society. PATIENTS/PARTICIPANTS: Patients on long-term bisphosphonates who presented with either periprosthetic fractures or femoral fractures, over a 10-year period. MAIN OUTCOME MEASUREMENTS: Time to union and complications. RESULTS: Clinically significant differences were identified in time to union, mortality, and complications. There was a statistically significant difference in complications. Imaging review demonstrated identical features in both atypical femoral fractures (AFFs) and PAFFs. CONCLUSIONS: This is the largest comparative case series reported on PAFFS and AFFs and provides compelling evidence that PAFFs in patients on long-term bisphosphonates are indeed a subset of periprosthetic fractures that exhibit atypical femoral fracture (AFF) characteristics. As such, these fractures pose serious diagnostic and management challenges to trauma and arthroplasty surgeons. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27003031 TI - Surgical Versus Nonsurgical Treatment of Adults With Displaced Fractures of the Proximal Humerus: The PROFHER Randomized Clinical Trial. PMID- 27003030 TI - A Review of Atypical Femoral Fractures From a Tertiary Care Teaching Hospital: An Alarming Trend? AB - OBJECTIVE: To evaluate the experience of a single tertiary care teaching hospital with the association between use of bisphosphonates and atypical femoral fractures, and to identify potential risk factors and chronologic incidence. DESIGN: Retrospective review. SETTING: Tertiary-care teaching hospital. PATIENTS: Thirty-two patients with a total of 43 fractures met inclusion criteria. INTERVENTION: Treatment for atypical femur fractures. MAIN OUTCOME MEASUREMENTS: Radiographic assessments, duration of bisphosphonate therapy, prodromal symptoms, associated medications/comorbidities. RESULTS: Thirty-one female patients and 1 male patient, with a total of 43 fractures, with an average age of 71.0 (47-92 years) +/- 11.01 years at time of fracture, had an average duration of bisphosphonate therapy of 7.57 (1-12 years) +/- 3.07 years. Prodromal thigh pain was reported in 20 of 43 fractures (46.5%). Eleven of the forty-three (25.5%) fractures occurred between 2001 and 2005. From 2006 to May 2011, however, 32/43 (74.5%) were reported. Beta-blockers, ACE/ARBs, and Statins (43.8%) were the most common concomitant medications, whereas Levothyroxine (21.8%), H-2 blockers (15.6%), and Glucocorticoids (12.5%) were less common. CONCLUSIONS: There is an increasing trend of atypical femur fractures in the current adult population. Bisphosphonate therapy beyond 7 years may place patients at increased risk. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27003035 TI - Atomic-scale insights into structural and thermodynamic stability of Pd-Ni bimetallic nanoparticles. AB - Atomic-scale understanding of structures and thermodynamic stability of core shell nanoparticles is important for both their synthesis and application. In this study, we systematically investigated the structural stability and thermodynamic evolution of core-shell structured Pd-Ni nanoparticles by molecular dynamics simulations. It has been revealed that dislocations and stacking faults occur in the shell and their amounts are strongly dependent on the core/shell ratio. The presence of these defects lowers the structural and thermal stability of these nanoparticles, resulting in even lower melting points than both Pd and Ni monometallic nanoparticles. Furthermore, different melting behaviors have been disclosed in Pd-core/Ni-shell and Ni-core/Pd-shell nanoparticles. These diverse behaviors cause different relationships between the melting temperature and the amount of stacking faults. Our results display direct evidence for the tunable stability of bimetallic nanoparticles. This study provides a fundamental perspective on core-shell structured nanoparticles and has important implications for further tailoring their structural and thermodynamic stability by core/shell ratio or composition controlling. PMID- 27003034 TI - Early antiretroviral therapy initiation in west Africa has no adverse social consequences: a 24-month prospective study. AB - Based on social indicators collected within the TEMPRANO-ANRS12136 trial, we assessed the social consequences of early antiretroviral therapy (ART) initiation in west Africa. We did not observe any significant differences in the levels or the time trends of various social indicators, including union status, HIV disclosure and HIV-related discrimination, between early and deferred ART initiation. Early ART does not carry detectable adverse social consequences that could impair its clinical and preventive benefits. PMID- 27003036 TI - Recent breakthroughs have unveiled the many knowledge gaps in Clostridium perfringens-associated necrotic enteritis in chickens: the first International Conference on Necrotic Enteritis in Poultry. PMID- 27003038 TI - Preferential alkali metal adduct formation by cis geometrical isomers of dicaffeoylquinic acids allows for efficient discrimination from their trans isomers during ultra-high-performance liquid chromatography/quadrupole time-of flight mass spectrometry. AB - RATIONALE: Caffeoylquinic acid (CQA) derivatives are a group of structurally diverse phytochemicals that have attracted attention due to their many health benefits. The structural diversity of these molecules is due in part to the presence of regio- and geometrical isomerism. This structural diversity hampers the accurate annotation of these molecules in plant extracts. Mass spectrometry (MS) is successfully used to differentiate between the different regioisomers of the CQA derivatives; however, the accurate discrimination of the geometrical isomers of these molecules has proven to be an elusive task. METHODS: UV irradiated methanolic solutions of diCQA were analyzed using an ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOFMS) method in negative ionisation mode. An in-source collision-induced dissociation (ISCID) method was optimized by varying both the capillary and cone voltages to achieve differential fragmentation patterns between UV-generated geometrical isomers of the diCQAs during MS analyses. RESULTS: Changes in the capillary voltage did not cause a significant difference to the fragmentation patterns of the four geometrical isomers, while changes in the cone voltage resulted in significant differences in the fragmentation patterns. The results also show, for the first time, the preferential formation of alkali metal (Li(+), Na(+) and K(+)) adducts by the cis geometrical isomers of diCQAs, compared to their trans counterparts. CONCLUSIONS: Optimized QTOFMS-based methods may be used to differentiate the geometrical isomers of diCQAs. Finally, additives such as metal salts to induce adduct formation can be applied as an alternative method to differentiate closely related isomers which could have been difficult to differentiate under normal MS settings. PMID- 27003037 TI - A phase 3, open-label study of daclatasvir plus asunaprevir in Asian patients with chronic hepatitis C virus genotype 1b infection who are ineligible for or intolerant to interferon alfa therapies with or without ribavirin. AB - BACKGROUND AND AIM: Daclatasvir plus asunaprevir has demonstrated efficacy and safety in patients with chronic hepatitis C virus genotype 1b infection. This study focused on evaluating daclatasvir plus asunaprevir in interferon (+/ ribavirin)-ineligible or -intolerant Asian patients with genotype 1b infection from mainland China, Korea, and Taiwan. METHODS: Interferon (+/-ribavirin) ineligible and -intolerant patients with genotype 1b infection received daclatasvir 60 mg tablets once daily plus asunaprevir 100 mg soft capsules twice daily for 24 weeks. The primary endpoint was sustained virologic response at post treatment week 24 (SVR24). RESULTS: Of the 159 patients treated, 89.3% were Chinese, 65.4% were female, and 73.6% were interferon-intolerant. Cirrhosis was present in 32.7% of patients, and 40.3% had IL28B non-CC genotypes. SVR24 was achieved by 145/159 (91.2%) patients (100% concordance with SVR12) and was similarly high in cirrhotic patients (47/52, 90.4%). SVR24 was higher in patients without baseline NS5A (L31M or Y93H) resistance-associated variants (RAVs) (137/139, 98.6%), including those with cirrhosis (43/44, 97.7%). Prevalence of baseline NS5A RAVs was low (19/159, 11.9%), particularly in mainland China (10/127, 7.9%). One death (0.6%), five serious adverse events (3.1%), and three grade 4 laboratory abnormalities (1.9%) occurred on treatment; none were considered related to study drugs. Two patients (1.3%) discontinued because of adverse events. Treatment was generally well tolerated regardless of cirrhosis status. CONCLUSIONS: Daclatasvir plus asunaprevir achieved a SVR24 rate of 91.2%, rising to 98.6% in patients without baseline NS5A RAVs, and was generally well tolerated in interferon (+/-ribavirin)-ineligible or -intolerant patients with genotype 1b infection from mainland China, Korea, and Taiwan. PMID- 27003039 TI - Mass spectrometric real-time monitoring of an enzymatic phosphorylation assay using internal standards and data-handling freeware. AB - RATIONALE: Continuous-flow reaction detection systems (monitoring enzymatic reactions with mass spectrometry (MS)) lack quantitative values so far. Therefore, two independent internal standards (IS) are implemented in a way that the online system stability can be observed, quantitative conversion values for substrate and product can be obtained and they can be used as mass calibration standards for high MS accuracy. METHODS: An application previously developed for the MS detection of peptide phosphorylation by cAMP-dependent protein kinase A (PKA) (De Boer et al., Anal. Bioanal. Chem. 2005, 381, 647-655) was transferred to a continuous-flow reaction detection system. This enzymatic reaction, involving enzyme activation as well as the transfer of a phosphate group from ATP to a peptide substrate, was used to prove the compatibility of a quantitative enzymatic assay in a continuous-flow real-time system (connected to MS). RESULTS: Moreover (using internal standards), the critical parameter reaction temperature (including solution density variations depending on temperature) was studied in the continuous-flow mixing system. Furthermore, two substrates (malantide and kemptide), two enzyme types (catalytic subunit of PKA and complete PKA) and one inhibitor were tested to determine system robustness and long-term availability. Even spraying solutions that contained significant amount of MS contaminants (e.g. the polluted catalytic subunit) resulted in quantifiable MS signal intensities. Subsequent recalculations using the internal standards led to results representing the power of this application. CONCLUSIONS: The presented methodology and the data evaluation with available Achroma freeware enable the direct coupling of biochemical assays with quantitative MS detection. Monitoring changes such as temperature, reaction time, inhibition, or compound concentrations can be observed quantitatively and thus enzymatic activity can be calculated. PMID- 27003040 TI - Towards matrix-free femtosecond-laser desorption mass spectrometry for in situ space research. AB - RATIONALE: There is an increasing interest in the quest for low molecular weight biomarkers that can be studied on extra-terrestrial objects by direct laser desorption mass spectrometry (LD-MS). Although molecular structure investigations have recently been carried out by direct LD-MS approaches, there is still a lack of suitable instruments for implementation on a spacecraft due to weight, size and power consumption demands. In this contribution we demonstrate the feasibility of LD-MS structural analysis of molecular species by a miniature laser desorption-ionization mass spectrometer (instrument name LMS) originally designed for in situ elemental and isotope analysis of solids in space research. METHODS: Direct LD-MS studies with molecular resolution were carried out by means of a Laser Ablation/Ionization Mass Spectrometry (LIMS) technique. Two polymer samples served as model systems: neutral polyethylene glycol (PEG) and cationic polymerizates of imidazole and epichlorohydrin (IMEP). Optimal conditions for molecular fragmentation could be identified for both polymers by tuning the laser energy and the instrument-sample distance. RESULTS: PEG and IMEP polymers show sufficient stability over a relatively wide laser energy range. Under mild LD conditions only moderate fragmentation of the polymers takes place so that valuable structural characterization based on fragment ions can be achieved. As the applied laser pulse energy rises, the abundance of fragment ions increases, reaches a plateau and subsequently drops down due to more severe fragmentation and atomization of the polymers. At this final stage, usually referred to as laser ablation, only elemental/isotope analysis can be achieved. CONCLUSIONS: Our investigations demonstrate the versatility of the LMS instrument that can be tuned to favourable laser desorption conditions that successfully meet molecule specific requirements and deliver abundant fragment ion signals with detailed structural information. Overall, the results show promise for use in similar studies on planetary surfaces beyond Earth where no or minimal sample preparation is essential. PMID- 27003041 TI - Mass fingerprint analysis of spider mites (Acari) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for rapid discrimination. AB - RATIONALE: Discrimination of spider mite species is still performed using morphological information, although DNA and other biological approaches have been attempted for identification purposes. These techniques need much time, are expensive, and require specialist staff. As an alternative, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) analysis is applied for rapid discrimination of spider mite species. METHODS: Spider mites were analyzed using MALDI-TOFMS after extraction with 70% formic acid and acetonitrile. A single spider mite was also analyzed directly on double-sided carbon tape. A dendrogram was compiled from the MS data. RESULTS: Evolutionarily close and morphologically similar spider mites, the Kanzawa (Tetranychus kanzawai) and the two-spotted (T. urticae) spider mites, as well as three other related species of spider mites, could be discriminated by mass fingerprints. Although female adults were mainly used in this report, male adults and nymphs showed almost the same mass fingerprints and were not considered to affect discrimination capability. A single spider mite on double-sided carbon tape was analyzed directly by MALDI-TOFMS. CONCLUSIONS: Spider mites could be analyzed directly by MALDI-TOFMS, with evolutionarily and morphologically closely related spider mites showing different mass fingerprints, allowing for their identification. PMID- 27003042 TI - Tandem mass spectrometry determination of the putative structure of a heterogeneous mixture of Lipid As isolated from the lipopolysaccharide of the Gram-negative bacteria Aeromonas liquefaciens SJ-19a. AB - RATIONALE: We report herein the electrospray ionization mass spectrometry (ESI MS) and low-energy collision-induced dissociation tandem mass spectrometry analysis (CID-MS/MS) of a mixture of lipid As isolated from the rough lipopolysaccharide (LPS) of the mutant wild strain of the Gram-negative bacteria Aeromonas liquefaciens (SJ-19a, resistant) grown in the presence of phages. The interaction between the phages and the Gram-negative bacteria regulates host specificity and the heterogeneity of the lipid A component of the LPS. METHODS: The heterogeneous mixture of lipid As was isolated by the aqueous phenol method from the LPS of the rough wild strain of Gram-negative bacteria Aeromonas liquefaciens (SJ-19a). Hydrolysis of the LPS was with 1% acetic acid, and purification was by chromatography using Sephadex G-50 and Sephadex G-15. ESI-MS and low-energy CID-MS/MS analyses were performed with a triple-quadrupole (QqQ) and a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. RESULTS: Preliminary analysis of the lipid As mixture was conducted by ESI-MS in the negative ion mode and the spectrum obtained suggested that the lipid A SJ-19a was composed of a heterogeneous mixture of different lipid A molecules. CID-MS/MS experiments confirmed the identities of the various mono-phosphorylated beta-D GlcpN-(1->6)-alpha-D-GlcpN disaccharide entities. This lipid As mixture was asymmetrically substituted with fatty acids such as ((R)-14:0(3-OH)), (14:0(3-(R) (O-12:0)) and (14:0(3-(R)-O-(14:0)) located on the O-3, O-3', N-2 and N-2' positions, respectively. CONCLUSIONS: Low-energy collision-induced dissociation tandem mass spectrometry in-space (QqQ-MS/MS) and in-time (FTICR-MS/MS) allowed the exact determination of the fatty acid acylation positions on the H2 PO3 ->4 O'-beta-D-GlcpN-(1->6)-alpha-D-GlcpN disaccharide backbones of this heterogeneous mixture of lipid As , composed inter alia of seven different substituted lipid As , formed from the incomplete biosynthesis of their respective LPS. PMID- 27003043 TI - Recombinant acetylated trypsin demonstrates superior stability and higher activity than commercial products in quantitative proteomics studies. AB - RATIONALE: Trypsin is an important digestive enzyme in peptide sample preparation for proteomics. It digests proteins at the C-terminal of Arg or Lys residues. The majority of commercial products are obtained from animal sources. In a previous study, we reported the production process for recombinant trypsin (r-trypsin) and acetylated trypsin (r-Ac-trypsin). In this paper, we want to evaluate whether the r-trypsin and r-Ac-trypsin are suitable for proteomics research. METHODS: The trypsins used in this research were first normalized to the same concentration and used for further evaluation. The stability and buffer compatibility (2M urea, 0.1% SDS and 10% acetonitrile) were compared and visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The digestion efficiency and specificity were compared based on a simple protein substrate, human serum albumin (HSA) and a complex proteomic sample, yeast lysate. The acquisition of proteomics data was achieved by ultra-high performance liquid chromatography (UPLC) connected to an LTQ Orbitrap Velos mass spectrometer. RESULTS: r-Ac trypsin demonstrated similar tolerance to 2 M urea and 10% acetonitrile but weaker 0.1% SDS tolerance than commercial trypsins. Based on simple protein sample HSA, the activity and specificity of r-Ac-trypsin were similar to that of commercial trypsins. However, it demonstrated superior activity and specificity on complicated samples like yeast lysate. More interestingly, the newly developed r-Ac-trypsin was more resistant to autolysis, which enabled more complete digestion of proteomic samples. CONCLUSIONS: The r-Ac-trypsin described here is a recombinant product. In addition it showed similar or superior properties such as stability activity and specificity to commercial products. It can be used in peptide sample preparation in proteomics studies. PMID- 27003044 TI - Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by human hepatocyte and liver microsome incubations and high-resolution mass spectrometry. AB - RATIONALE: AMB (methyl (1-pentyl-1H-indazole-3-carbonyl)-L-valinate)) and its fluoro analog 5F-AMB (methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)-L valinate) are two new synthetic cannabinoids that are structural analogs of AB PINACA and 5F-AB-PINACA, respectively. 5F-AMB is scheduled as an illicit drug in China, Germany, Singapore and Japan, and no metabolism data are currently available for either drug. The aim of the present work was to investigate the metabolism of AMB and 5F-AMB and propose appropriate markers to identify their intake in clinical or forensic cases. METHODS: AMB and 5F-AMB were incubated in human hepatocytes (10 MUmol/L) to generate phase I and II metabolites, which were identified with a TripleTOF 5600(+) high-resolution mass spectrometer. AMB and 5F AMB metabolic stability studies also were performed with human liver microsomes (HLM) to evaluate metabolic clearances, and to adequately design the human hepatocyte experiment. RESULTS: AMB and 5F-AMB were quickly metabolized in HLM with a 1.1 +/- 0.1 and 1.0 +/- 0.2 min T1/2, respectively. The predominant metabolic pathway for AMB and 5F-AMB in hepatocytes was ester hydrolysis, and further oxidation and/or glucuronidation. In total, 19 metabolites were identified for AMB and 17 for 5F-AMB. We describe metabolites to differentiate AMB from 5F-AMB, and metabolites that are common to both analytes due to oxidative defluorination of 5F-AMB. CONCLUSIONS: For the first time, AMB and 5F AMB metabolism profiles were characterized, providing valuable data for identifying these two novel psychoactive substances. The difficulties of differentiating AMB and 5F-AMB from AB-PINACA/5F-AB-PINACA metabolites also were examined. These data improve the interpretation of urinary markers after AMB and 5F-AMB intake. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27003045 TI - Design and performance evaluation of a novel ion funnel driven by a phase modulated rectangular wave. AB - RATIONALE: The ion funnel has proven to be an important ion transport device. It is used in mass spectrometry as a replacement for the ion transmission limited skimmer. However, conventional out-of-phase radiofrequency (RF) supply approaches inevitably produce potential barriers, decreasing transmission efficiency. A novel RF supply method is proposed that produces better transmission performance. METHODS: We designed an ion funnel driven by a phase-modulated rectangular wave (PMRW). The potential field distributions of the PMRW ion funnel and a conventional ion funnel were computer simulated to evaluate their focusing properties. A series of simulations were produced using the SIMION ion-optics simulation program to compare the transmission efficiency of the two types of funnel. Preliminary experimental results were obtained using an electrospray ionization mass spectrometry platform with polypropylene glycol, propylamine and butylamine samples. RESULTS: The electrical potential distribution of a PMRW ion funnel has a bowl shape at the cross section of the electrodes, rather than in the field-free region; this benefits focusing performance. A comparison of ion trajectories and flight time data produced by the SIMION simulations showed that the potential barrier did not exist in the PMRW mode. The experimental results showed that the PMRW method increased the signal intensity by 150-200% for propylamine and butylamine and 50% for polypropylene glycol. CONCLUSIONS: A novel PMRW ion funnel has been designed and developed. The simulation and experimental results indicate that the PMRW ion funnel has better transmission efficiency than the conventional ion funnel, particularly for low mass-to-charge ratio ions. PMID- 27003046 TI - Extension of the Q Orbitrap intrascan dynamic range by using a dedicated customized scan. AB - RATIONALE: The intrascan dynamic range of modern Orbitrap instrumentation is specified to reach 1:5000, while the interscan dynamic range is significantly larger due to the utilization of the automatic gain control feature. There are some applications (e.g. residue analysis in complex matrices, metabolomics or structural elucidation) where a wider intrascan dynamic range is desirable. METHODS: The Application Programming Interface (API) of the Q Exactive Orbitrap mass spectrometer has been used to program a customized scan in order to cover a larger intrascan dynamic range. Different approaches were used, which were all based on the variation of the isolation time of low-abundance versus high abundance mass range segments. The differently attenuated mass range segments isolated by the quadrupole were sequentially forwarded to the C-trap. Finally, the accumulated mass segments were measured within the Orbitrap analyzer. RESULTS: The spectra obtained by the customized scans show an enlarged dynamic range. This has been demonstrated by monitoring the higher isotope mass peaks (first and second isotope) of a low intensity analyte. Furthermore, a practical application (veterinary drugs in bovine kidney) has been investigated with the proposed customized scan. Analytes eluting within the retention time region of very intense matrix peaks (e.g. peptides) showed improved detectability when utilizing the customized scan. CONCLUSIONS: The extension of the intrascan dynamic range by a customized scan is helpful when analyzing residues which happen to elute together with a dominating matrix peak or within a high ion abundance region (e.g. dead volume). Furthermore, this feature helps in the process of determining the elemental composition of compounds by permitting the investigation of low-abundance ions (e.g. belonging to the isotopic fine structure of the investigated compound). PMID- 27003047 TI - Polydimethylsiloxane microchannel coupled to surface acoustic wave nebulization mass spectrometry. PMID- 27003048 TI - Men (and Women) in Academic Radiology: How Can We Reduce the Gender Discrepancy? AB - OBJECTIVE: There is a chronic gender imbalance in academic radiology departments, which could limit our field's ability to foster creative, productive, and innovative environments. We recently reviewed 51 major academic radiology faculty rosters and discovered that 34% of academic radiologists are women, but only 25% of vice chairs and section chiefs and 9% of department chairs are women. CONCLUSION: Active intervention is needed to correct this imbalance, which should start with awareness of the issue, exposing medical students to radiology early in their training, and implementing better mentorship programs for female radiologists. PMID- 27003049 TI - Whole-Tumor Quantitative Apparent Diffusion Coefficient Histogram and Texture Analysis to Predict Gleason Score Upgrading in Intermediate-Risk 3 + 4 = 7 Prostate Cancer. AB - OBJECTIVE: The objective of our study was to evaluate whole-lesion quantitative apparent diffusion coefficient (ADC) for the prediction of Gleason score (GS) upgrading in 3 + 4 = 7 prostate cancer. MATERIALS AND METHODS: Fifty-four patients with GS 3 + 4 = 7 prostate cancer diagnosed at systematic transrectal ultrasound (TRUS)-guided biopsy underwent 3-T MRI and radical prostatectomy (RP) between 2012 and 2014. A blinded radiologist contoured dominant tumors on ADC maps using histopathologic correlation. The whole-lesion mean ADC, ADC ratio (normalized to peripheral zone), ADC histogram, and texture analysis were compared between tumors with GS upgrading and those without GS upgrading using multivariate ROC analyses and logistic regression modeling. RESULTS: Tumors were upgraded to GS 4 + 3 = 7 after RP in 26% (n = 14) of the 54 patients, and tumors were downgraded after RP in none of the patients. The mean ADC, ADC ratio, 10th centile ADC, 25th-centile ADC, and 50th-centile ADC were similar between patients with GS 3 + 4 = 7 tumors (0.99 +/- 0.22, 0.58 +/- 0.15, 0.77 +/- 0.31, 0.94 +/- 0.28, and 1.15 +/- 0.24, respectively) and patients with upgraded GS 4 + 3 = 7 tumors (1.02 +/- 0.18, 0.55 +/- 0.11, 0.71 +/- 0.26, 0.89 +/- 0.20, and 1.11 +/- 0.16) (p > 0.05). Regression models combining texture features improved the prediction of GS upgrading. The combination of kurtosis, entropy, and skewness yielded an AUC of 0.76 (SE = 0.07) (p < 0.001), a sensitivity of 71%, and a specificity of 73%. The combination of kurtosis, heterogeneity, entropy, and skewness yielded an AUC of 0.77 (SE = 0.07) (p < 0.001), a sensitivity of 71%, and a specificity of 78%. CONCLUSION: In this study, whole-lesion mean ADC, ADC ratio, and ADC histogram analysis were not predictive of pathologic upgrading of GS 3 + 4 = 7 prostate cancer after RP. ADC texture analysis improved accuracy. PMID- 27003050 TI - Association of Medial Meniscus Extrusion With the Prominence of a Fascicular Capsulofemoral Band Subjacent to the Deep Medial Collateral Ligament. AB - OBJECTIVE: The objective of our study was to test our hypothesis that a transverse oblique fascicular anteromedial capsulofemoral band partially subjacent to the deep medial collateral ligament (MCL) is more prominent in knees with medial meniscal extrusion. MATERIALS AND METHODS: We retrospectively analyzed all knee MRI examinations from a 6-month period for the presence and dimensions of the anteromedial capsulofemoral band on coronal proton-density fat saturated images and also for medial meniscus extrusion, which was defined as extrusion of 3 mm or greater. Edemalike signal intensity within or in the vicinity of the anteromedial capsulofemoral band, partial or complete tears of the MCL, a history of MCL surgery, or a neoplastic mass lesion violating the medial supporting structures were exclusion criteria. We reviewed procedural videos of patients who subsequently underwent knee arthroscopy. MRI of a cadaveric knee was performed and was followed by dissection and histologic examination. RESULTS: MRI examinations of 346 knees of 312 patients met the inclusion criteria; of these knees, 50 had medial meniscus extrusion. The anteromedial capsulofemoral band was discernible on MRI in all knees except five (98.6%), and it was visible in six of the arthroscopy videos of 17 knees. The anteromedial capsulofemoral band was thicker on MRI of patients with medial meniscus extrusion (p < 0.0001). The anteromedial capsulofemoral band was identified on MRI and at dissection of the cadaveric knee, and histologic examination revealed that the anteromedial capsulofemoral band was a capsuloligamentous structure. CONCLUSION: A transverse oblique anteromedial capsulofemoral band subjacent to the deep MCL is thicker in knees with medial meniscus extrusion. PMID- 27003051 TI - Prominent Inferior Intercavernous Sinus on Sagittal T1-Weighted Images: A Sign of Intracranial Hypotension. AB - OBJECTIVE: The purpose of this study is to describe the diagnostic accuracy of the dilatation of the inferior intercavernous sinus as a sign of intracranial hypotension and to raise awareness of this anatomic structure, which can be mistaken for a focal pituitary lesion. MATERIALS AND METHODS: Sagittal T1 weighted images of 26 patients with intracranial hypotension and 28 control subjects were evaluated to determine the presence of a distended inferior intercavernous sinus. Information about the shape, size, and signal of the inferior intercavernous sinus was also collected. The chi-square test was used to compare both groups. Sensitivity and specificity of the dilatation of the inferior intercavernous sinus as a sign of intracranial hypotension were calculated. RESULTS: A visible inferior intercavernous sinus was found in 13 of 26 patients with intracranial hypotension (50%) and in four of 28 control subjects (14.3%). These percentages were significantly different (p = 0.005). There was no significant difference in size of the inferior intercavernous sinus in the intracranial hypotension group (median, 5.86 mm(2); interquartile range, 6.28 mm(2)) compared with the control group (median, 8.25 mm(2); interquartile range, 16.69 mm(2)). Changes in the size of the inferior intercavernous sinus were detected in congruence with the appearance or resolution of intracranial hypotension. CONCLUSION: Dilatation of the inferior intercavernous sinus is frequently associated with intracranial hypotension, although it can also be found in the healthy adult as a normal anatomic variant. Recognition of this anatomic structure is important to avoid mistaking it for a focal pituitary lesion. PMID- 27003052 TI - Mummified Thyroid Syndrome. AB - OBJECTIVE: The purpose of this article is to highlight the various sonographic characteristics that should help to differentiate a restructured benign collapsed thyroid nodule from histologically proven thyroid carcinoma by different imaging means, including Doppler sonography, and fine-needle aspiration cytologic analysis. CONCLUSION: Benign thyroid nodules may display morphologic changes over time, which can have misleading sonographic features suggestive of malignancy. Precise knowledge of certain sonographic imaging features, such as regular eggshell calcifications, peripheral hypoechoic or hypoechoic rim, posterior shadowing, and absence of intranodular vascularization, and meticulous comparison with previous images showing thyroid nodule shrinkage over time are useful for reaching the correct final diagnosis. Fine-needle aspiration cytologic assessment of such initially suspicious thyroid nodules and sonographic follow-up contribute to establishing the final diagnosis of benign thyroid findings. Knowledge of the elements described should help to identify the so-called mummified thyroid nodule and avert surgical excision. PMID- 27003053 TI - FDG Avidity and Tumor Burden: Survival Outcomes for Patients With Recurrent Breast Cancer. AB - OBJECTIVE: The objective of this study was to assess the value of quantitative PET parameters in the prediction of survival for patients with recurrent breast cancer. MATERIALS AND METHODS: We conducted a retrospective study of 78 women who had recurrent breast cancer identified by biopsy or follow-up examinations from 2000 to 2012. The maximum and peak standardized uptake values (SUVmax and SUVpeak, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured for each recurrent lesion at primary, nodal, and distant metastatic sites, with the use of the gradient segmentation method. The optimum cutoff point (i.e., the value with the maximum Youden index, defined as sensitivity plus specificity minus 1) was calculated using the ROC curve. The median follow-up duration was 28.5 months (range, 0-94 months). The primary outcome measure was overall survival (OS). Kaplan-Meier survival plots and Cox regression analyses were performed. RESULTS: The mean (+/- SD) values noted for the study population were as follows: an SUVmax of 6.70 +/- 4.1, an SUVpeak of 5.12 +/- 3.4, total lesion glycolysis of all recurrent lesions (TLGtotal) of 359.73 +/- 1114.4 g, and metabolic tumor volume of all recurrent lesions (MTVtotal) of 68.04 +/- 144.9 mL. The mean OS for patients who died was 25.5 months, whereas for patients who survived, it was 36.7 months (p = 0.04). Univariate analysis showed that age (p = 0.02), optimum SUVmax (p = 0.006), SUVpeak (p = 0.006), and TLGtotal (p = 0.034) were associated with OS; however, none of the factors remained statistically significant in multivariate analysis. Kaplan-Meier survival analysis was performed, and the SUVmax (threshold, 2.9; hazard ratio [HR], 5.2 [95% CI, 1.6-16.7]; p = 0.002), SUVpeak (threshold, 2.34; HR, 4.3 [95% CI, 1.5-12]; p = 0.002), and TLG (threshold, 11.85 g; HR, 2.8 [95% CI, 1.0-7.1]; p = 0.025) were statistically significant predictors of death during follow-up. An integrated risk stratification model with FDG avidity (SUVmax) and MTVtotal divided into three subgroups of patients predicted patient survival outcomes (HR, 2.48 [95% CI, 1.38-4.46]; p = 0.005, by log-rank test). CONCLUSION: FDG PET-determined SUVmax, SUVpeak, and TLG values and an integrated risk stratification scheme using FDG avidity and total tumor burden appear to provide prognostic survival information for patients with recurrent breast cancer. PMID- 27003054 TI - Correlation of Observed-to-Expected MRI Fetal Lung Volume and Ultrasound Lung-to Head Ratio at Different Gestational Times in Fetuses With Congenital Diaphragmatic Hernia. AB - OBJECTIVE: The purpose of this study is to compare the observed-to-expected MRI fetal lung volume and the observed-to-expected ultrasound lung-to-head ratio intraindividually for prediction of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD) at different times of gestation (< 28, 28-32, and > 32 weeks) in fetuses with congenital diaphragmatic hernia (CDH), and to analyze the intraindividual correlation of observed-to-expected MRI fetal lung volume and observed-to expected ultrasound lung-to-head ratio. MATERIALS AND METHODS: Two hundred one fetuses were included in our study. Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio were calculated for 270 MRI and ultrasound examinations performed within 72 hours of each other. The prognostic accuracy of observed-to-expected MRI fetal lung volume and observed-to expected ultrasound lung-to-head ratio was assessed by performing ROC analysis. Correlation was determined using linear regression analysis. RESULTS: The results revealed statistically significant differences between the observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio for the prediction of survival, the need for ECMO therapy, and the development of CLD in fetuses with left-sided CDH (p <= 0.0444), with the highest prognostic accuracy for survival (AUC = 0.863). Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio correlated statistically significantly (p < 0.0001) for left-sided CDH with correlation coefficients (r) of 0.71, 0.71, and 0.56 for early, intermediate, and late times of gestation, respectively. The correlation was not statistically significant at any time for right-sided CDH (p >= 0.3947; r <= 0.26). CONCLUSION: Observed-to-expected MRI fetal lung volume and observed-to-expected ultrasound lung-to-head ratio are valuable prognostic parameters for prenatal prediction of survival, the need for ECMO therapy, and the development of CLD in fetuses with left-sided CDH at all times of gestation. Observed-to-expected MRI fetal lung volume and observed-to expected ultrasound lung-to-head ratio correlate statistically significantly for left-sided CDH, and the correlation is best before 32 weeks' gestation, but they do not correlate statistically significantly for right-sided CDH. PMID- 27003055 TI - Contribution of FDG PET/CT for the Optimization of the Management of Additional Lesions Detected on Local Staging Breast MRI. AB - OBJECTIVE: The purpose of this study is to evaluate the added value of FDG PET/CT for the management of additional lesions detected by breast MRI during initial staging of known breast cancer. MATERIALS AND METHODS: We retrospectively queried our database for all consecutive patients with biopsy-confirmed breast cancer who underwent breast MRI and FDG PET/CT before neoadjuvant chemotherapy between November 2011 and November 2012. The final population comprised 80 patients. Initially, two readers retrospectively analyzed the breast MRI data for the presence of lesions in addition to the previously confirmed index neoplasm. Analysis of FDG PET/CT data followed; two different readers evaluated the presence or absence of FDG uptake in both breasts. The reference standard for additional lesions was percutaneous biopsy with subsequent 2-year follow-up for benign results. Statistical analysis was conducted with nonparametric analysis and the Fisher exact test. RESULTS: The readers detected 61 additional breast lesions at MRI in 45 patients (56.2%); 37 of 61 (61%) additional lesions were malignant and 24 of 61 (39%) were benign. Among the 61 additional breast lesions detected by MRI, only 32 were positive at FDG PET/CT, with a positive predictive value of 90.6% and negative predictive value of 72%. The sensitivity, specificity, and accuracy of FDG PET/CT were 78.3%, 87.5%, and 81.9%, respectively. In eight cases, FDG PET/CT missed additional malignant lesions. All missed malignant additional lesions were smaller than 1 cm. In three cases, additional lesions also detected at FDG PET/CT were benign. CONCLUSION: In the case of additional lesions detected at MRI, a negative FDG PET/CT finding could replace a breast biopsy for lesions larger than 1 cm. PMID- 27003056 TI - Corrections. PMID- 27003057 TI - Medicolegal-Malpractice and Ethical Issues in Radiology. PMID- 27003058 TI - Sonographic Detection of Perirenal Transplant Hematomas. PMID- 27003059 TI - Overdiagnosis Versus Misdiagnosis of Pulmonary Embolism. PMID- 27003060 TI - Reply to "Overdiagnosis Versus Misdiagnosis of Pulmonary Embolism". PMID- 27003061 TI - Authorship for Leading Journals: Issue on Ethical Problems. PMID- 27003062 TI - A review of sulfide emissions in sewer networks: overall approach and systemic modelling. AB - The problems related to hydrogen sulfide in terms of deterioration of sewer networks, toxicity and odor nuisance have become very clear to the network stakeholders and the public. The hydraulic and (bio)chemical phenomena and parameters controlling sulfide formation, emission and their incidences in sewer networks are very complex. Recent research studies have been developed in gravity and pressure sewers and some transfer models have been published. Nevertheless, the models do not take into account all the physical phenomena influencing the emission process. After summing up the main scientific knowledge concerning the production, oxidation, transfer and emission processes, the present review includes: (i) a synthetic analysis of sulfide and hydrogen sulfide emission models in sewer networks, (ii) an estimation of their limit, (iii) perspectives to improve the modelling approach. It shows that sulfide formation and uptake models still need refinements especially for some phenomena such as liquid to gas mass transfer. Transfer models that have been published so far are purposely simplified and valid for simple systems. More efforts have to be undertaken in order to better understand the mechanisms and the dynamics of hydrogen sulfide production and emission in real conditions. PMID- 27003063 TI - Spatial and temporal variations of water quality in an artificial urban river receiving WWTP effluent in South China. AB - Urban wastewater treatment plant (WWTP) effluent as reclaimed water provides an alternative water resource for urban rivers and effluent will pose a significant influence on the water quality of rivers. The objective of this study was to investigate the spatial and temporal variations of water quality in XZ River, an artificial urban river in Shenzhen city, Guangdong Province, China, after receiving reclaimed water from WWTP effluent. The water samples were collected monthly at different sites of XZ River from April 2013 to September 2014. Multivariate statistical techniques and a box-plot were used to assess the variations of water quality and to identify the main pollution factor. The results showed the input of WWTP effluent could effectively increase dissolved oxygen, decrease turbidity, phosphorus load and organic pollution load of XZ River. However, total nitrogen and nitrate pollution loads were found to remain at higher levels after receiving reclaimed water, which might aggravate eutrophication status of XZ River. Organic pollution load exhibited the lowest value on the 750 m downstream of XZ River, while turbidity and nutrient load showed the lowest values on the 2,300 m downstream. There was a higher load of nitrogen and phosphorus pollution in the dry season and at the beginning of wet season. PMID- 27003064 TI - Partial nitrification in MBBRs for mainstream deammonification with thin biofilms and alternating feed supply. AB - A new principle for mainstream nitrogen removal through nitritation followed by anammox was studied in a two-stage moving bed biofilm reactor (MBBR) configuration. The first stage was optimized for nitritation by using thin biofilms and a feed alternating between synthetic mainstream wastewater at 15 degrees C and, for shorter periods, synthetic reject water at 30 degrees C. The exposure of the biofilm to reject water conditions aimed to improve the growth conditions for ammonia oxidizing bacteria, while inhibiting nitrite oxidizing bacteria. The biofilm thickness was maintained below 200 MUm to ensure high exposure of the total biomass to the bulk reactor conditions. Nitritation was successfully achieved in the configuration, with a nitrite accumulation ratio above 75% during the majority of the study, and ammonia removal rates between 0.25 and 0.50 g NH4-N/L,d. The anoxic second stage, optimized for anammox, was fed with the effluent from the nitritation reactor, reaching nitrogen removal rates above 0.20 g TN/L,d. PMID- 27003065 TI - Nutrient removal performance and microbial characteristics of a full-scale IFAS EBPR process treating municipal wastewater. AB - This work describes the nutrient removal performance and microbial characteristics of a full-scale integrated fixed-film activated sludge-enhanced biological phosphorus removal (IFAS-EBPR) process for municipal wastewater treatment. The polymerase chain reaction-denaturing gradient gel electrophoresis results showed that the presence of bacteria in this process, including Nitrosomonas sp., Nitrospira sp., Nitrobacter sp., Pseudomonas sp. and Acinetobacter sp., clusters. The fluorescence in situ hybridization results implied that there were more nitrifiers and denitrifiers on the biofilm carriers than in the suspended sludge, whereas more phosphorus-accumulating organisms (PAOs) resided in the suspended sludge. With the cooperation of these functional microbial populations both on the biofilm carriers and in the suspended sludge, the chemical oxygen demand (COD), NH4(+)-N, total nitrogen (TN) and total phosphorus (TP) removal efficiencies were maintained at 84, 97, 70 and 81%, and the effluent concentrations of them averaged 30, 1.0, 11.5 and 0.6 mg/L, which all satisfy the Chinese discharge standard (COD <50 mg/L, NH4(+)-N <5 mg/L, TN <15 mg/L and TP <1 mg/L), respectively. Therefore, the IFAS-EBPR process is a reliable and effective process for nutrient removal. PMID- 27003066 TI - Removal of sunset yellow FCF from aqueous solution using polyethyleneimine modified MWCNTs. AB - A novel adsorbent consisting of polyethyleneimine-modified multi-wall carbon nanotubes (PEI-MWCNTs) was synthesized by grafting PEI on the carboxyl MWCNTs. The surface properties of the PEI-MWCNTs were measured by scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared, and zeta potential. The adsorption behavior of the PEI-MWCNTs was investigated using sunset yellow FCF as adsorbate. The effects of dosage of adsorbent, the initial pH of solution, contact time and temperature on the adsorption capacity were studied. Then, the kinetics and thermodynamics of the adsorption process were further investigated. Experimental results showed that the adsorption kinetics fitted a pseudo-second-order model and the adsorption isotherms agreed well with the Langmuir model. The adsorption process occurred very fast and the adsorption capacity of PEI-MWCNTs was much higher than that of many of the previously reported adsorbents. Additionally, the plausible adsorption mechanism was discussed. PMID- 27003067 TI - Hexavalent chromium removal performance of anionic functionalized monolithic polymers: column adsorption, regeneration and modelling. AB - Anionic functionalized monolithic macro-porous polymers were used for the removal of hexavalent chromium(VI) anions from aqueous solution in column experiments. At a flux of 1.0 cm min and 30 mg Cr(VI) L(-1) feed concentration, breakthrough capacity and apparent capacity were 0.066 g Cr(VI) g(-1) anionic monolith and 0.144 g Cr(VI) g(-1) anionic monolith, respectively. The degree of column utilization was found to lie in the range 41-46%. Two kinetic models, theoretical and Thomas models, were applied to experimental data to predict the breakthrough curves and to determine the characteristic parameters of the column useful for process design. The simulation of the whole breakthrough curve was effective with the models. At a flux of 1.0 cm min and 30 mg Cr(VI) L(-1) feed concentration, the dispersion coefficient and adsorption equilibrium constant (K) were 3.14 * 10(-7) m s(-1) and 3,840, respectively. Also, Thomas model parameters k1 (rate constant of adsorption) and qm (equilibrium solid-phase concentration of sorbed solute) were 1.08 * 10(-3) L mg(-1) min(-1) and 0.124 g g(-1), respectively. After reaching equilibrium adsorption capacity, the monoliths were regenerated using 1 N HCl and were subsequently re-tested. It was found that the regeneration efficiency reduced from 98% after second usage to 97% after the third usage. PMID- 27003068 TI - Local-scale recovery of wastewater nitrogen for edible plant growth. AB - An anaerobic/ion exchange (AN-IX) system was developed for recovery and reuse of wastewater nitrogen at point-of-origin. AN-IX combines upflow solids blanket anaerobic treatment with ammonium ion adsorption onto granular natural zeolite. AN-IX operates passively and without energy input. A 57 L empty-bed prototype was operated for 355 days on wastewater primary effluent. Total nitrogen removal exceeded 95% over the first 214 days of operation and ammonia reduction exceeded 99%; accumulation of oxidized nitrogen species (NO3(-) + NO2(-)) was not observed. The wastewater flowrate was increased during the last 35 days of operation to deliberately exhaust the ion exchange media. Spent granular media was removed from the AN-IX prototype and deployed in plant chamber experiments for cultivation of Solanum lycopersicum (cherry tomato). Wastewater nitrogen captured on zeolite was capable of supplying the total growth requirement for nitrogen. Canopy volume and plant flowering and fruiting were higher for wastewater nitrogen than for artificial fertilizer. The AN-IX process is a passive, mechanically simple and reliable system for local-scale nitrogen recovery. AN-IX is modular, scalable, adaptable and can be applied in diverse treatment contexts and recycling scenarios. AN-IX benefits include appropriate technology for local-scale nitrogen recovery, low capital and energy costs, and protection of health and the environment. PMID- 27003069 TI - Enhanced sonochemical degradation of tetracycline by sulfate radicals. AB - Tetracyclines (TCs) are widely used antibiotics in human and veterinary medicine and as growth promoters in the world. Sulfate radical-based advanced oxidation processes have been of great interest due to the high oxidizing potential of sulfate radical to degrade refractory organic pollutants in aqueous solution. In this study, the degradation of antibiotic TC in aqueous solution by silver activated persulfate (Na2S2O8) in the presence of ultrasound irradiation under various conditions has been investigated. The effects of several parameters such as Ag2SO4, Na2S2O8 concentration, temperature, ultrasonic (US) power, initial TC concentration and initial pH on the degradation of TC were investigated. More than 83% of TC removal was achieved within 120 min under optimal conditions. The optimum operational conditions were found to be as follows: Ag2SO4 dosage 3.5 mmol/L, Na2S2O8 concentration 70 mmol/L, reaction temperature 25 degrees C, US power 120 W, initial TC concentration 50 mg/L, pH 3.0 and contact time 120 min. The degradation of TC in the persulfate/Ag(+)/US process followed the pseudo first-order kinetics. PMID- 27003070 TI - Comparative study of raw and chemically treated mangrove leaf for remediation of 304 Methyl Violet 2B dye from aqueous solution: thermo-kinetics aspect. AB - The adsorption process is the most attractive alternative way for the treatment of industrial effluents. The main objective of the study is to compare the efficacy of adsorption by raw and chemically treated forms of mangrove plant leaf powder. It acts as adsorbent, and would not only be economical but also help to reduce pollution. The adsorbent was characterized by Fourier transform infra-red spectroscopy and scanning electron microscopy. Results showed that percent removal of dye was higher by chemically treated mangrove leaf (98%) than by raw mangrove leaf (75%) under all determined conditions. The equilibrium and kinetics adsorption data were analyzed by the Langmuir isotherm and the pseudo second order model. They were found to be the best fit to interpret the present data. The thermodynamic parameters were calculated by using the Langmuir equilibrium constant. Results suggested that dye adsorption on mangrove leaf was a spontaneous and exothermic process with enthalpy change = -15.26 kJ/mol, and there was decrease in disorder with entropy change = -5.089 kJ/mol K. PMID- 27003071 TI - Treatment of soil eluate containing nitro aromatic compounds by adsorption on activated coke (AC). AB - Soil washing is a kind of physical method to remove organic matters from contaminated soil. However, its eluate after washing may result in secondary pollution to the environment. In this study, activated coke (AC) was used to remove organic pollutants from contaminated soil eluate. The effect of temperature, initial chemical oxygen demand (COD) and AC dosage on COD removal efficiency was investigated. The results showed that the organic matter can be removed in the eluate because the COD dropped a lot. When the AC dosage was 20 g.L(-1), 88.92% of COD decreased after 480 min of adsorption at 50 degrees C. The process of adsorption can be described by the Redlich-Peterson isotherm. The adsorption was spontaneous and endothermic. The pseudo-second-order model can be used to describe the adsorption process. After adsorption, the acute toxicity of the eluate was reduced by 76%, and the water qualities were in agreement with Chinese discharge standard GB 14470.1-2002, which means the eluate could be discharged to the environment. PMID- 27003072 TI - Modelling the influence of total suspended solids on E. coli removal in river water. AB - Following sewer overflows, fecal indicator bacteria enter surface waters and may experience different lysis or growth processes. A 1D mathematical model was developed to predict total suspended solids (TSS) and Escherichia coli concentrations based on field measurements in a large-scale flume system simulating a combined sewer overflow. The removal mechanisms of natural inactivation, UV inactivation, and sedimentation were modelled. For the sedimentation process, one, two or three particle size classes were incorporated separately into the model. Moreover, the UV sensitivity coefficient alpha and natural inactivation coefficient kd were both formulated as functions of TSS concentration. It was observed that the E. coli removal was predicted more accurately by incorporating two particle size classes. However, addition of a third particle size class only improved the model slightly. When alpha and kd were allowed to vary with the TSS concentration, the model was able to predict E. coli fate and transport at different TSS concentrations accurately and flexibly. A sensitivity analysis revealed that the mechanisms of UV and natural inactivation were more influential at low TSS concentrations, whereas the sedimentation process became more important at elevated TSS concentrations. PMID- 27003073 TI - In situ microscopy as a tool for the monitoring of filamentous bacteria: a case study in an industrial activated sludge system dominated by M. parvicella. AB - The present study demonstrates the application of in situ microscopy for monitoring the growth of filamentous bacteria which can induce disturbances in an industrial activated sludge process. An in situ microscope (ISM) is immersed directly into samples of activated sludge with Microthrix parvicella as dominating species. Without needing further preparatory steps, the automatic evaluation of the ISM-images generates two signals: the number of individual filaments per image (ISM-filament counting) and the total extended filament length (TEFL) per image (ISM-online TEFL). In this first version of the image processing algorithm, closely spaced crossing filament-segments or filaments within bulk material are not detected. The signals show highly linear correlation both with the standard filament index and the TEFL. Correlations were further substantiated by comparison with real-time polymerase chain reaction (real-time PCR) measurements of M. parvicella and of the diluted sludge volume index. In this case study, in situ microscopy proved to be a suitable tool for straightforward online-monitoring of filamentous bacteria in activated sludge systems. With future adaptation of the system to different filament morphologies, including cross-linking filaments, bundles, and attached growth, the system will be applicable to other wastewater treatment plants. PMID- 27003074 TI - Evaluation of the applicability of the SWAT model in an arid piedmont plain oasis. AB - Hetao Oasis is located in a typical piedmont alluvial plain bounded by the Langshan Mountain Range in the north, desert in the west, and the Yellow River in the south. Agricultural activities within the oasis significantly impact the hydrological cycle and water quality in downstream locations. The research uses the Soil and Water Assessment Tool (SWAT) for a piedmont plain by defining the watershed boundary as coinciding with the natural mountain ridge, the border between the oasis and the desert, and the Yellow River. The model simulates water discharge with coefficient of determination and a Nash-Sutcliffe model efficiency of 0.78 and 0.62 during model calibration, and 0.75 and 0.69 during model validation, suggesting that delineation of the watershed as carried out in this research is suitable for piedmont plain topography. From the results, the mountains contribute 28.4% to the water discharge at the outlet of the watershed, and water-use efficiency of irrigated water is about 40%, which is consistent with field-based measurements. Methodologies used in delineating watershed boundaries and parameterizing SWAT provide a solid foundation for water balance studies in other regions of the world with similar topography. PMID- 27003075 TI - Efficiency of wastewater treatment in SBR and IFAS-MBSBBR systems in specified technological conditions. AB - The objective of this study is to compare wastewater treatment effectiveness in sequencing batch reactor (SBR) and integrated fixed-film activated sludge-moving bed sequencing batch biofilm reactor (IFAS-MBSBBR) systems in specific technological conditions. The comparison of these two technologies was based on the following assumptions, shared by both series, I and II: the reactor's active volume was 28 L; 8-hour cycle of reactor's work, with the same sequence and duration of its consecutive phases; and the dissolved oxygen concentration in the aerobic phases was maintained at a level of 3.0 mg O2/L. For both experimental series (I and II), comparable effectiveness of organic compound (chemical oxygen demand (COD)) removal, nitrification and biological phosphorus removal has been obtained at levels of 95.1%, 97% and 99%, respectively. The presence of the carrier improved the efficiency of total nitrogen removal from 86.3% to 91.7%. On the basis of monitoring tests, it has been found that the ratio of simultaneous denitrification in phases with aeration to the total efficiency of denitrification in the cycle was 1.5 times higher for IFAS-MBSBBR. PMID- 27003076 TI - Treatment of wastewater containing o-phenylenediamine by ozone in a rotor-stator reactor. AB - This work employed a novel rotor-stator reactor (RSR) to intensify the degradation process of o-phenylenediamine (o-PDA) by ozone. The effects of different operating parameters including initial pH, temperature, rotation speed, liquid volumetric flow rate and inlet ozone concentration on the removal efficiency of o-PDA were investigated in an attempt to establish the optimum conditions. The removal efficiency was evaluated in terms of degradation ratio and chemical oxygen demand (COD) reduction ratio of the o-PDA wastewater. Results indicate that the removal efficiency decreased with increasing liquid volumetric flow rate but increased with an increase in pH and inlet ozone concentration. Also, the removal efficiency increased up to a certain level with an increase in rotation speed and temperature. Additionally, a comparison experiment was carried out in a stirred tank reactor (STR), and the results show that the degradation and COD reduction ratios reached a maximum of 94.6% and 61.2% in the RSR as compared to 45.3% and 28.6% in the STR, respectively. This work demonstrates that ozone oxidation carried out in RSR may be a promising alternative for pre treatment of o-PDA wastewater. PMID- 27003077 TI - Complete solids retention activated sludge process. AB - In a slaughterhouse's full-scale extended aeration activated sludge wastewater treatment plant (WWTP), operating under complete solids retention time, the evolution of mixed liquor suspended solids (MLSS) and mixed liquor volatile suspended solids (MLVSS) concentration, food to micro-organisms ratio (F/M) and substrate utilization rate (SUR) were studied for over a year. Biomass growth phases in correlation to sludge biological and morphological characteristics were studied. Three distinguished growth phases were observed during the 425 days of monitoring. The imposed operational conditions led the process to extended biomass starvation conditions, minimum F/M, minimum SUR and predator species growth. MLSS and MLVSS reached a stabilization phase (plateau phase) where almost zero sludge accumulation was observed. The concept of degradation of the considered non-biodegradable particulate compounds in influent and in biomass (cell debris) was also studied. Comparison of evolution of observed sludge yields (Yobs) in the WWTP with Yobs predictions by activated sludge models verified the degradation concept for the considered non-biodegradable compounds. Control of the sedimentation process was achieved, by predicting the solids loading rate critical point using state point analysis and stirred/unstirred settling velocity tests and by applying a high return activated sludge rate. The nitrogen gas related sedimentation problems were taken into consideration. PMID- 27003078 TI - The effect of electromagnetic fields, from two commercially available water treatment devices, on bacterial culturability. AB - Commercially available pulsed-electromagnetic field (PEMF) devices are currently being marketed and employed to ostensibly manage biofouling. The reliable application and industry acceptance of such technologies require thorough scientific validation - and this is currently lacking. We have initiated proof-of principle research in an effort to investigate whether such commercially available PEMF devices can influence the viability (culturability) of planktonic bacteria in an aqueous environment. Thus two different commercial PEMF devices were investigated via a static (i.e. non-flowing) treatment system. 'Healthy' Escherichia coli cells, as well as cultures that were physiologically compromised by silver nano-particles, were exposed to the PEMFs from both devices under controlled conditions. Although relatively minor, the observed effects were nevertheless statistically significant and consistent with the hypothesis that PEMF exposure under controlled conditions may result in a decrease in cellular viability and culturability. It has also been observed that under certain conditions bacterial growth is actually stimulated. PMID- 27003079 TI - Porous calcium niobate nanosheets prepared by an exfoliation-restacking route. AB - The single phase layered perovskite-type niobate KCa2Nb3O10 was obtained by a solid state reaction of the starting materials (K2CO3, CaCO3 and Nb2O5) at 1,200 degrees C. Then the H(+)-exchanged form (HCa2Nb3O10) was successfully exfoliated into colloidal porous single layers on the intercalating action of tetra(butyl)ammonium ion. The various characterization techniques such as X-ray diffraction (XRD), field-emission scanning electron microscopy, N2 absorption desorption and diffuse reflectance UV-visible spectrometry gave important information on the unusual structural features of the perovskite-related niobate nanosheets. XRD analysis of the exfoliated nanosheets showed a unique profile with wide peaks that represented individual molecular aspects of the nanosheets. The Brunauer-Emmett-Teller isotherm of the exfoliated coiled nanosheets showed a sharp increase in the surface area by a factor of >30 in comparison to parent layered material, which is due to the exfoliation and restacking process. The nanosheets in this study were also found to act as a semiconductor with a wide band gap that is due to the quantum size effect. PMID- 27003080 TI - Environmental performance of wastewater reuse systems: impact of system boundaries and external conditions. AB - Wastewater reclamation will be a significant part of future water management and the environmental assessment of various treatment systems to reuse wastewater has become an important research field. The secondary treatment process and sludge handling on-site are, especially, electricity demanding processes due to aeration, pumping, mixing, dewatering, etc. used for operation and are being identified as the main contributor for many environmental impacts. This study discusses how the environmental performance of reuse treatment systems may be influenced by surrounding conditions. This article illustrates and discusses the importance of factors commonly treated as externalities and as such not being included in optimization strategies of reuse systems, but that are necessary to environmentally assess wastewater reclamation systems. This is illustrated by two up-stream and downstream processes; electricity supply and the use of sludge as fertilizer commonly practiced in regions considered for wastewater reclamation. The study shows that external conditions can have a larger impact on the overall environmental performance of reuse treatment systems than internal optimizations could compensate for. These results imply that a more holistic environmental assessment of reuse schemes could provide less environmental impacts as externalities could be included in measures to reduce the overall impacts. PMID- 27003081 TI - Fate of phthalate esters in municipal wastewater treatment plant and their environmental impact. AB - The fate and distribution of six phthalate esters (PAEs) in a municipal wastewater treatment plant (WWTP) employing an anaerobic/anoxic/oxic (A(2)/O) process were investigated. The process achieved relatively high removal efficiencies of PAEs in the range 55-97%. It illustrated that biotransformation and sludge-adsorption were major elimination pathways by analyzing the mass balance and flux of PAEs. About 83% of ?PAEs was entirely removed by A(2)/O bioreactors indicating biotransformation is the dominant removal mechanism. PAEs with shorter alkyl chain length and higher water solubility were more biodegradable. Less than 6% of ?PAEs were removed by excess sludge adsorption. The sludge-adsorption capacity of PAE depends on its hydrophobicity. The levels and fluxes of PAEs were analyzed by monitoring different sites of the receiving river of the WWTP effluent to clarify the potential impact of discharge. Daily flux of PAEs upstream and downstream of the discharging point were 113 kg.d(-1) and 205 kg.d(-1), respectively, which were higher than the effluent devotion value of 6.67 kg.d(-1). It suggested that the emissions from the WWTP appeared to be less than those from the other possible sources, such as potential untreated discharge and surface runoff. Improvement of wastewater collection efficiencies is necessary to eliminate the PAE load in the urban river. PMID- 27003082 TI - The effects of Parachlorella kessleri cultivation on brewery wastewater. AB - Bioindustrial wastewaters, often characterised by high carbon and nitrogen contents, have shown promise as a valuable resource for the cultivation of beneficial microorganisms. The purpose of this study was to assess if Parachlorella kessleri could utilise brewery wastewater (Br WW) for growth and production of metabolites. P. kessleri was cultivated on different concentrations of Br WW over 14 days. Higher concentrations of Br WW led to an approximate two fold increase in dry cell weight yielding a maximum of 12.3 g DCW/L. High glucose and nitrogen utilisation was associated with high algal biomass yields, with a 97% reduction in glucose achieved in 50% (v/v) Br WW cultures after 14 days. Assessing the benefits to P. kessleri, increases in oleic and alpha-linoleic acids were seen in 50 and 10% (v/v) Br WW cultures. Concentration of Br WW did not have an impact on the overall antioxidant activities of microalgal cultures, however, it did affect phenolic levels (2.4-fold increase) in 50% (v/v) Br WW cultures. This research demonstrated that P. kessleri did utilise the carbon and nitrogen content in the Br WW for growth and metabolite production, thereby reducing the nutrient load of the Br WW. PMID- 27003083 TI - A clinoptilolite-PDMS mixed-matrix membrane for high temperature water softening. AB - A mixed-matrix membrane composed of polydimethylsiloxane (PDMS) as the continuous phase and clinoptilolite, a naturally occurring zeolite, as the active phase has been used to decrease the conductivity of water by more than 80% across the membrane. Testing was carried out using a cross-flow configuration at temperatures as high as 160 degrees C using a constant transmembrane pressure of 8 bar. The simple fabrication method for the membrane, the durability of the system under the test conditions, and a suitable flux rate make such membranes promising candidates for industrial wastewater treatment. PMID- 27003084 TI - Continuous flow electrocoagulation in the treatment of wastewater from dairy industries. AB - Dairy industry wastewater contains high levels of organic matter, consisting mainly of fat, protein and products of their partial microbial decomposition. In the present study, the use of continuous electrocoagulation is proposed for the primary treatment of dairy wastewater. The electrochemical treatment was carried out in a continuous flow cell with aluminum electrodes. The influence of the voltage, the distance between the electrodes and the hydraulic residence time (HRT) on the process performance was assessed, by measuring the removal of color, turbidity, total organic carbon (TOC) and chemical oxygen demand (COD). The optimum voltage, distance between the electrodes and HRT were 10 V, 1 cm and 90 min, respectively, yielding a current density of 13.3 A.m(-2). Under these conditions, removal of color, turbidity, TOC and COD were 94%, 93%, 65% and 69%, respectively, after a steady state was reached in the continuous flow reactor. PMID- 27003085 TI - The color removal and fate of organic pollutants in a pilot-scale MBR-NF combined process treating textile wastewater with high water recovery. AB - A combination of membrane bioreactor (MBR) and nanofiltration (NF) was tested at pilot-scale treating textile wastewater from the wastewater treatment station of a textile mill in Wuqing District of Tianjin (China). The MBR-NF process showed a much better treatment efficiency on the removal of the chemical oxygen demand, total organic carbon, color and turbidity in comparison with the conventional processes. The water recovery rate was enhanced to over 90% through the recycling of NF concentrate to the MBR, while the MBR-NF showed a stable permeate water quality that met with standards and could be directly discharged or further reused. The recycled NF concentrate caused an accumulation of refractory compounds in the MBR, which significantly influenced the treatment efficiency of the MBR. However, the sludge characteristics showed that the activated sludge activity was not obviously inhibited. The results of fluorescence spectra and molecular weight distribution indicated that those recalcitrant pollutants were mostly protein-like substances and a small amount of humic acid-like substances (650-6,000 Da), which contributed to membrane fouling of NF. Although the penetrated protein-like substances caused the residual color in NF permeate, the MBR-NF process was suitable for the advanced treatment and reclamation of textile wastewater under high water yield. PMID- 27003086 TI - Microfiltration of vinasse: sustainable strategy to improve its nutritive potential. AB - The purpose of this article was to evaluate and establish microfiltration (MF) operating conditions for vinasse (ethanol industries wastewater also known as stillage, slop, distillery effluent or dunder) concentration aiming to improve the use of its nutritive potential. The operating conditions influence permeate flux that has been evaluated by monitoring the flow rate profile during the operation on bench scale in different conditions (feed pH, aeration condition and recovery rate). From the results found, the process scale up was then effected. The bench scale findings showed that the vinasse microfiltration under air flow of 0.5 m(3).h(-1) between membrane fibers, with no pH adjustment, and recovery rate of 93% produced two flows, one of permeate that may be used to wash the sugarcane during the ethanol production processing, and the other of concentrate that contains a high organic compounds and nutrients concentration. This concentrate has additional potentiality of being used as organic compound supplement in contaminated soil bioremediation, and as a supplier of microbial biomass or substrate for biosurfactant production. PMID- 27003087 TI - Effect of calcium oxide on the efficiency of ferrous ion oxidation and total iron precipitation during ferrous ion oxidation in simulated acid mine drainage treatment with inoculation of Acidithiobacillus ferrooxidans. AB - Calcium oxide was added into ferrous ion oxidation system in the presence of Acidithiobacillus ferrooxidans at concentrations of 0-4.00 g/L. The pH, ferrous ion oxidation efficiency, total iron precipitation efficiency, and phase of the solid minerals harvested from different treatments were investigated during the ferrous ion oxidation process. In control check (CK) system, pH of the solution decreased from 2.81 to 2.25 when ferrous ions achieved complete oxidation after 72 h of Acidithiobacillus ferrooxidans incubation without the addition of calcium oxide, and total iron precipitation efficiency reached 20.2%. Efficiency of ferrous ion oxidation and total iron precipitation was significantly improved when the amount of calcium oxide added was <=1.33 g/L, and the minerals harvested from systems were mainly a mixture of jarosite and schwertmannite. For example, the ferrous ion oxidation efficiency reached 100% at 60 h and total iron precipitation efficiency was increased to 32.1% at 72 h when 1.33 g/L of calcium oxide was added. However, ferrous ion oxidation and total iron precipitation for jarosite and schwertmannite formation were inhibited if the amount of calcium oxide added was above 2.67 g/L, and large amounts of calcium sulfate dihydrate were generated in systems. PMID- 27003088 TI - Mesquite wood chips (Prosopis) as filter media in a biofilter system for municipal wastewater treatment. AB - The biofiltration system over organic bed (BFOB) uses organic filter material (OFM) to treat municipal wastewater (MWW). This study evaluated the performance of a BFOB system employing mesquite wood chips (Prosopis) as OFM. It also evaluated the effect of hydraulic loading rates (HLRs) in order to achieve the operational parameters required to remove organic matter, suspended material, and pathogens, thus meeting Mexican and US regulations for reuse in irrigation. Two biofilters (BFs) connected in series were installed; the first one aerated (0.62 m(3)air m(-2)h(-1)) and the second one unaerated. The source of MWW was a treatment plant located in Durango, Mexico. For 200 days, three HLRs (0.54, 1.07, and 1.34 m(3)m(-2)d(-1)) were tested. The maximum HLR at which the system showed a high removal efficiency of pollutants and met regulatory standards for reuse in irrigation was 1.07 m(3)m(-2)d(-1), achieving removal efficiencies of biochemical oxygen demand (BOD5) 92%, chemical oxygen demand (COD) 78%, total suspended solids (TSS) 95%, and four log units of fecal coliforms. Electrical conductivity in the effluent ensures that it would not cause soil salinity. Therefore, mesquite wood chips can be considered an innovative material suitable as OFM for BFs treating wastewaters. PMID- 27003089 TI - Adsorption of crystal violet with diatomite earth&carbon by a modification of hydrothermal carbonization process. AB - The high colority and difficulty of decolorization are the most important tasks on printing and dyeing wastewater. This study investigates the ability of diatomite earth&carbon (DE&C) as an adsorbent to removal crystal violet (CV) from aqueous solutions. Fourier transform infrared spectroscopy results indicate the importance of functional groups during the adsorption of CV. The obtained N2 adsorption-desorption isotherm values accord with well IUPAC type II. Our calculations determined a surface area of 73.15 m(2) g(-1) for DE&C and an average pore diameter of 10.56 nm. Equilibrium data of the adsorption process fitted very well to the Langmuir model (R(2) > 0.99). The results of kinetics study showed that the pseudo-second-order model fitted to the experimental data well. The thermodynamic parameters were also evaluated. DeltaH degrees <0, DeltaS degrees > 0 and DeltaG degrees < 0 demonstrated that the adsorption process was spontaneous and exothermic for dye. Furthermore the positive value of DeltaS degrees reflected good affinity of the CV dye. PMID- 27003090 TI - Probability distribution of turbulence in curvilinear cross section mobile bed channel. AB - The present study investigates the probability density functions (PDFs) of two dimensional turbulent velocity fluctuations, Reynolds shear stress (RSS) and conditional RSSs in threshold channel obtained by using Gram-Charlier (GC) series. The GC series expansion has been used up to the moments of order four to include the skewness and kurtosis. Experiments were carried out in the curvilinear cross section sand bed channel at threshold condition with uniform sand size of d50 = 0.418 mm. The result concludes that the PDF distributions of turbulent velocity fluctuations and RSS calculated theoretically based on GC series expansion satisfied the PDFs obtained from the experimental data. The PDF distribution of conditional RSSs related to the ejections and sweeps are well represented by the GC series exponential distribution, except that a slight departure of inward and outward interactions is observed, which may be due to weaker events. This paper offers some new insights into the probabilistic mechanism of sediment transport, which can be helpful in sediment management and design of curvilinear cross section mobile bed channel. PMID- 27003091 TI - An investigation into the relationship between water quality volume (design storage volume) and stormwater wetland performance. AB - An investigation on free water surface wetland, which has an area of 0.23 ha and is employed to control the non-point source pollution from a watershed of 7.4 ha, was carried out to examine how the WQvr (the ratio of stormwater inflow volume to water quality volume (WQv)) affects the wetland treatment performance. As stormwater went through the wetland, TSS (total suspended solids), TCOD (total chemical oxygen demand), TN (total nitrogen) and TP (total phosphorus) were reduced by 85%, 57%, 6% and 68%, on average, respectively. Increase in the WQvr resulted in a decrease in the reduction efficiencies of TSS, TCOD and TP, but a slight increase in TN removal. WQv was identified as a useful parameter for the design of stormwater wetlands, as this volumetric design approach overcomes the variation in flow rate and pollutant concentrations with respect to time and rainfall conditions. However, the design goal of 80% TSS reduction was not accomplished as inflow water volume equal to designed WQv. On the other hand, it was found that TCOD and TP reduction could also be considered as wetland design goals together with TSS. However, TN reduction did not show any significant relationship with the WQv. PMID- 27003092 TI - Corrigendum: Water Science and Technology 72 (9), 1543-1551: Feasibility of anaerobic membrane bioreactors (AnMBR) for onsite sanitation and resource recovery (nutrients, energy and water) in urban slums, doi: 10.2166/wst.2015.349. PMID- 27003093 TI - The effect of cannabinoids on the stretch reflex in multiple sclerosis spasticity. AB - The aim of this observational study was to assess the efficacy of a tetrahydrocannabinol-cannabidiol (THC : CBD) oromucosal spray on spasticity using the stretch reflex in patients with multiple sclerosis (MS). Numeric rating scale (NRS) for spasticity, modified Ashworth scale (MAS), and the stretch reflex were assessed before and during treatment in 57 MS patients with spasticity eligible for THC : CBD treatment. A significant reduction in stretch reflex amplitude as well as significant reductions of NRS and MAS scores were observed. There was a low concordance between the three measures (stretch reflex, NRS, and MAS), likely related to the different aspects of muscle hypertonia assessed. Stretch reflex responders were taking a significantly higher number of puffs, whereas no differences were found in the responders by the other scales, suggesting that a higher dosage would add benefit if tolerated. The present study confirms the efficacy of cannabinoids in reducing spasticity in patients with MS, suggesting a higher sensitivity and specificity of the stretch reflex compared with other measures. As an objective and quantitative measure of spasticity, the stretch reflex is particularly useful to assess the effects of cannabinoids on spinal excitability and may play a role in future pharmacological studies. PMID- 27003094 TI - Use of Boswellia-based cream for prevention of adjuvant radiotherapy skin damage in mammary carcinoma. PMID- 27003095 TI - Primary Metastatic Synovial Sarcoma: Experience of the CWS Study Group. AB - BACKGROUND: Prognostic factors for localized synovial sarcoma are well defined. However, few data exist regarding patients with metastases at diagnosis. Poor outcome is described but the optimal therapeutic regimen remains unclear. Our aim was to assess the outcome, identify prognostic factors, and analyze treatment strategies. METHODS: Patients <21 years with synovial sarcoma and primary distant metastases treated in the consecutive prospective European Cooperative Weichteilsarkom Studiengruppe trials 1980-2010 were analyzed. RESULTS: Twenty nine of 296 patients had primary metastases. Twenty-seven could be included. Median age was 16.7 years. Primaries were mainly located in the limbs (78%) and 74% were >=10 cm. Metastases involved the lungs in all patients. Two patients presented with synchronous bone metastases. Sixty-three percent of patients achieved a first remission, whereas only 26% maintained it. Relapses were metastatic with pulmonary metastases in nearly all patients. Five-year event-free survival and overall survival (OS) rates were 26% and 30%, respectively. Prognosis was best for patients with oligometastatic lung metastases (5-year OS probability 85%). Prognosis was worse for patients with multiple bilateral lung metastases (5-year OS 13%) and even poorer for those with concurrent bone metastases. Treatment elements associated with superior survival were adequate local therapy of the primary tumor and, if feasible, for metastases, chemotherapy with an ifosfamide/doxorubicin-based regimen. The use of whole lung irradiation was not correlated with better outcomes. CONCLUSIONS: The overall prognosis of primary metastatic synovial sarcoma is poor. However, individuals with oligometastatic lung metastases had very good chance for long-term survival when treated with adequate multimodal therapy. PMID- 27003096 TI - Dental Applications of Natural-Origin Polymers in Hard and Soft Tissue Engineering. AB - Clinical advances in the treatment of dentoalveolar defects continue to evolve with the introduction of new innovations in regenerative medicine and tissue bioengineering. Recent developments in tissue engineering are aimed at safely and effectively regenerating a damaged or necrotic area by replenishing its cells and increasing surrounding gene expression. Various techniques have successfully given rise to porous scaffolds being used by clinicians to treat the defect and initiate the repair process. Tissue reconstruction using bioengineered scaffolds is advantageous over traditional autografting, since it prevents the instigation of pain and donor site morbidity while ultimately creating both the environment and machinery needed to induce cell proliferation, migration, and reattachment within the affected area. This review article aims to describe and review the available literature regarding the regenerative capacity of natural polymers used for the treatment of dentoalveolar defects. The repair mechanisms, advantages of protein and polysaccharide derivatives, and the potential of stem cell therapy are discussed. PMID- 27003097 TI - An Update on Calcineurin Inhibitor-Free Regimens: The Need Persists, but the Landscape has Changed. AB - Calcineurin inhibitors (CNIs) have failed to improve long-term renal allograft survival. Their association with cardiovascular morbidity in addition to their suboptimal inhibition of a chronic alloimmune response has shifted investigative efforts toward CNI-free regimens. Sotrastaurin, a small molecule targeting protein kinase C isoforms, failed to provide adequate immunosuppression, whereas the Janus kinase 3 inhibitor tofacitinib's success in the treatment of rheumatoid arthritis led to biopharma's abandonment of it as a transplant agent. Like tofacitinib, tocilizumab, a biologic targeting the IL-6 pathway, has been approved for use in rheumatoid arthritis and interest in transplantation has been confined to several investigator-initiated trials. Belatacept, a second generation, higher avidity variant of CTLA4Ig (abatacept), was approved by the Food and Drug Administration for prophylaxis of transplant rejection in 2011. Long-term follow-up of recipients on belatacept has demonstrated superior glomerular filtration rates as compared with CNIs, albeit with an increased risk of early and histologically severe rejection. Focus on optimizing belatacept inclusive regimens has led to studies using lymphocyte depletion as induction and maintenance therapy with target of rapamycin inhibitors. ASKP1240, the most advanced of the anti-CD40 antibodies targeting the CD40/CD154 costimulatory pathway has just completed a phase II trial with a CNI-free arm. Animal models suggest that its highest efficacy may be in combination with belatacept. Finally, nonagonistic CD28 antibodies, which would allow CTLA4 and PD-LI binding of CD80/CD86 and activation of inhibitory pathways, have re-emerged with 2 anti-CD28 candidates in preclinical development. A reliable nontoxic CNI-free regimen may ultimately require the combination of biologic agents that provide efficacy as well as safety. PMID- 27003098 TI - Risk Factors for BK Polyoma Virus Treatment and Association of Treatment With Kidney Transplant Failure: Insights From a Paired Kidney Analysis. AB - BACKGROUND: Identification of risk factors for BK polyoma virus (BKPyV) without confounding by donor factors and era effects in paired analysis may inform strategies to prevent BKPyV. METHODS: In this analysis of 21,575 mate kidney pairs in the Scientific Registry of Transplant Recipients between 2004 and 2010, the presence of a treatment code for BKPyV virus in follow-up forms was used to identify pairs in which 1 of 2 mate kidneys was treated (discordant treatment) or both mate kidneys were treated (concordant treatment). RESULTS: Among 1975 discordant pairs, younger than 18 years or 60 years or older, male sex, HLA mismatch or 4 greater, acute rejection, and depleting antibody induction had a higher odds of treatment, whereas diabetes and sirolimus had a lower odds of treatment, and treatment was associated with a higher risk of allograft failure (hazards ratio, 2.01; 95% confidence interval, 1.63-2.48). The rate of concordant treatment (0.81%) was 2.8 times higher than expected. Concordant treatment was associated with nonwhite donor ethnicity, donation after circulatory death, transplantation after 2008, and transplantation of mate kidneys in the same center. CONCLUSIONS: This analysis of kidneys from the same donor in which only 1 transplant was treated for BKPyV identifies specific risk factors (age <18 or >= 60 years, male sex, depleting antibody, HLA mismatch >= 4) for BKPyV and provides an estimate of the BKPyV-associated risk of allograft failure (hazards ratio = 2.01) without confounding by donor factors or era effects. The higher than expected rate of concordant treatment suggests the importance of donor factors in BKPyV pathogenesis and warrants further study. PMID- 27003099 TI - Capillary Thrombosis in the Skin: A Pathologic Hallmark of Severe/Chronic Rejection of Human Vascularized Composite Tissue Allografts? AB - BACKGROUND: Vascularized composite tissue allografts (VCA) can undergo rejection, manifesting pathologically with skin changes that form the basis of the Banff 2007 classification of VCA rejection. METHODS: We have followed 10 human VCA recipients (7 with hand allografts, 3 with face allografts) for pathological signs of rejection. All of them developed episodes of acute rejection. Two patients with hand allografts presented in some of their skin biopsies an as yet unreported pathological finding in human VCA, consisting of capillary thromboses (CT) in the upper dermis. RESULTS: Capillary thrombosis was associated with other typical changes of grade II to III VCA rejection, namely, perivascular T cell infiltrates, but not with vascular C4d deposits (in formalin-fixed tissue). Clinically, the lesions presented as red or violaceous (lichenoid) cutaneous maculopapules. The first patient had several episodes of acute rejection during the 7-year follow-up. The second patient developed donor-specific antibodies; some months after CT were first observed, he developed chronic rejection leading to partial amputation of the allograft. Pathological examination of the skin showed graft vasculopathy and occasional C4d deposits in cutaneous capillaries. CONCLUSIONS: Capillary thrombosis seems to be a novel pathologic finding associated with human VCA rejection. Although its mechanism (immunologic vs nonimmunologic) remains unclear, this finding could carry an unfavorable prognostic significance, prompting close monitoring of the patients for severe/chronic rejection. PMID- 27003100 TI - Platelet function in diabetic and nondiabetic patients with chronic obstructive pulmonary disease: a case control study. AB - BACKGROUND: The effect of association between chronic obstructive pulmonary disease (COPD) and diabetes (DM) on platelet function has not been studied before. OBJECTIVES: To evaluate the effect of the association between COPD and DM on platelet function and C reactive protein (CRP). PATIENTS AND METHODS: This case control study was carried out on 110 stable COPD patients who were classified into diabetic and nondiabetic groups. In addition, 40 apparently healthy, age and sex-matched individuals were included in this study as a control group. Chest X-ray, pulmonary function testing and arterial blood gases were done for COPD patients. CRP and complete blood count (CBC) were measured in both patient and control groups. RESULTS: Mean platelet volume (MPV), platelet distribution width (PDW), platelet crit (PCT) and CRP were significantly higher in COPD patients either nondiabetic or diabetic compared to control group. Moreover, MPV and CRP markers were significantly higher in COPD diabetic patients compared to nondiabetic. There was no significant difference in various laboratory data among different stages of COPD either diabetic or nondiabetic (P > 0.05). In COPD patients, MPV was a significantly positively correlated with CRP and PDW (r = 0.346, P < 0.001; r = 0.510, P < 0.001, respectively) and negatively correlated with PLT count (r = -0.294, P = 0.002). CONCLUSION: MPV, PDW, PCT and CRP were significantly higher in COPD patients either nondiabetic or diabetic. Platelet function may be modified by the systemic inflammation that associated with COPD. Platelet activation as a prothrombotic sequence of this disease may be used as novel therapeutic target. PMID- 27003101 TI - Interrogating the Role of Receptor-Mediated Mechanisms: Biological Fate of Peptide-Functionalized Radiolabeled Gold Nanoparticles in Tumor Mice. AB - To get a better insight on the transport mechanism of peptide-conjugated nanoparticles to tumors, we performed in vivo biological studies of bombesin (BBN) peptide functionalized gold nanoparticles (AuNPs) in human prostate tumor bearing mice. Initially, we sought to compare AuNPs with thiol derivatives of acyclic and macrocyclic chelators of DTPA and DOTA types. The DTPA derivatives were unable to provide a stable coordination of (67)Ga, and therefore, the functionalization with the BBN analogues was pursued for the DOTA-containing AuNPs. The DOTA-coated AuNPs were functionalized with BBN[7-14] using a unidentate cysteine group or a bidentate thioctic group to attach the peptide. AuNPs functionalized with thioctic-BBN displayed the highest in vitro cellular internalization (~ 25%, 15 min) in gastrin releasing peptide (GRP) receptor expressing cancer cells. However, these results fail to translate to in vivo tumor uptake. Biodistribution studies following intravenous (IV) and intraperitoneal (IP) administration of nanoconjugates in tumor bearing mice indicated that the presence of BBN influences to some degree the biological profile of the nanoconstructs. For IV administration, the receptor-mediated pathway appears to be outweighed by the EPR effect. By contrast, in IP administration, it is reasoned that the GRPr-mediated mechanism plays a role in pancreas uptake. PMID- 27003104 TI - Ordered Self-Similar Patterns in Anisotropic Stochastic Growth. AB - We propose an anisotropic stochastic growth model to rationalize the anisotropic self-assembly of supramolecules to form elongated two-dimensional ribbon structures in a recent experiment. The model exhibits distinct growth scenarios that are critically controlled by the ratio of the transverse and the longitudinal growth rate. In the regime of suppressed transverse growth, the model generates the experimentally observed elongated structures through layer-by layer growing. We further observe the convergence of rough clusters toward smooth regular elliptic patterns by averaging over a number of independent growth processes. Remarkably, these resulting elliptic clusters are self-similar in each instantaneous moment in the growth process. Statistical analysis suggests that the realization of such ordered patterns does not rely on the delicate coordination of different parts in the cluster growth. The self-similarity phenomenon derived from this idealized model may have wider implications, notably in the designed clustering of various elementary building blocks with anisotropic interactions. PMID- 27003103 TI - Highly Dynamic Interactions Maintain Kinetic Stability of the ClpXP Protease During the ATP-Fueled Mechanical Cycle. AB - The ClpXP protease assembles in a reaction in which an ATP-bound ring hexamer of ClpX binds to one or both heptameric rings of the ClpP peptidase. Contacts between ClpX IGF-loops and clefts on a ClpP ring stabilize the complex. How ClpXP stability is maintained during the ATP-hydrolysis cycle that powers mechanical unfolding and translocation of protein substrates is poorly understood. Here, we use a real-time kinetic assay to monitor the effects of nucleotides on the assembly and disassembly of ClpXP. When ATP is present, complexes containing single-chain ClpX assemble via an intermediate and remain intact until transferred into buffers containing ADP or no nucleotides. ATP binding to high affinity subunits of the ClpX hexamer prevents rapid dissociation, but additional subunits must be occupied to promote assembly. Small-molecule acyldepsipeptides, which compete with the IGF loops of ClpX for ClpP-cleft binding, cause exceptionally rapid dissociation of otherwise stable ClpXP complexes, suggesting that the IGF-loop interactions with ClpP must be highly dynamic. Our results indicate that the ClpX hexamer spends almost no time in an ATP-free state during the ATPase cycle, allowing highly processive degradation of protein substrates. PMID- 27003102 TI - Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma. AB - Mutations in histone acetyltransferases (HATs) are among the most common mutations in diffuse large B-cell lymphoma (DLBCL). We previously showed that two human DLBCL cell lines, RC-K8 and SUDHL2, express C-terminally truncated, HAT domain-deficient p300 proteins (p300DeltaC) that are required for optimal cell proliferation. Microarray analysis of mRNA expression in RC-K8 cells following p300DeltaC knockdown shows upregulation of NF-kappaB and p53 gene expression programs and downregulation of a MYC gene expression program. Experiments indicate that these gene expression changes are due to inhibitory effects of p300DeltaC on NF-kappaB activity and on p53 protein levels and stimulatory effects on MYC protein levels, suggesting that p300DeltaC mutants enhance the proliferation of DLBCL cells by adjusting the transcriptional output of cell specific oncoproteins. We propose that p300/CBP gene truncation represents a new class of oncogenic mutation that optimizes the activity of context-specific oncogenic transcription factors. We propose 'oncogenic modifier' to describe such mutations. PMID- 27003105 TI - ASA must be given to classify multiple NSAID-hypersensitivity patients as selective or cross-intolerant. PMID- 27003106 TI - Timing Correlations in Proteins Predict Functional Modules and Dynamic Allostery. AB - How protein structure encodes functionality is not fully understood. For example, long-range intraprotein communication can occur without measurable conformational change and is often not captured by existing structural correlation functions. It is shown here that important functional information is encoded in the timing of protein motions, rather than motion itself. I introduce the conditional activity function to quantify such timing correlations among the degrees of freedom within proteins. For three proteins, the conditional activities between side-chain dihedral angles were computed using the output of microseconds-long atomistic simulations. The new approach demonstrates that a sparse fraction of side-chain pairs are dynamically correlated over long distances (spanning protein lengths up to 7 nm), in sharp contrast to structural correlations, which are short-ranged (<1 nm). Regions of high self- and inter-side-chain dynamical correlations are found, corresponding to experimentally determined functional modules and allosteric connections, respectively. PMID- 27003107 TI - Correction to 'Spontaneity is a meticulously prepared art': Commentary on Taber et al. (2016). PMID- 27003109 TI - Interplay of Nitrogen-Atom Inversion and Conformational Inversion in Enantiomerization of 1H-1-Benzazepines. AB - A series of 2,4-disubstituted 1H-1-benzazepines, 2a-d, 4, and 6, were studied, varying both the substituents at C2 and C4 and at the nitrogen atom. The conformational inversion (ring-flip) and nitrogen-atom inversion (N-inversion) energetics were studied by variable-temperature NMR spectroscopy and computations. The steric bulk of the nitrogen-atom substituent was found to affect both the conformation of the azepine ring and the geometry around the nitrogen atom. Also affected were the Gibbs free energy barriers for the ring flip and the N-inversion. When the nitrogen-atom substituent was alkyl, as in 2a c, the geometry of the nitrogen atom was nearly planar and the azepine ring was highly puckered; the result was a relatively high-energy barrier to ring-flip and a low barrier to N-inversion. Conversely, when the nitrogen-atom substituent was a hydrogen atom, as in 2d, 4, and 6, the nitrogen atom was significantly pyramidalized and the azepine ring was less puckered; the result here was a relatively high energy barrier to N-inversion and a low barrier to ring-flip. In these N-unsubstituted compounds, it was found computationally that the lowest energy stereodynamic process was ring-flip coupled with N-inversion, as N inversion alone had a much higher energy barrier. PMID- 27003108 TI - Comparing human papillomavirus vaccine knowledge and intentions among parents of boys and girls. AB - BACKGROUND/OBJECTIVE: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Previous research suggests some differences between male and female adolescents in correlates of vaccine receipt and reasons for non-vaccination; few studies examine both sexes together. This analysis assessed knowledge and attitudes related to HPV disease and vaccination, intention to vaccinate, and reasons for delayed vaccination or non-vaccination among parents of boys and girls 13-17 y old in 50 states, the District of Columbia, and selected local areas. METHODS: National Immunization Survey-Teen 2013 data were analyzed and gender differences examined. RESULTS: In this sample, adolescent boys were more likely than girls to be unvaccinated and less likely to have completed the HPV vaccination series (p < 0.005 for both). Parents of girls were more likely than parents of boys to report a provider recommendation for HPV vaccination (65.0% vs. 42.1%). Only 29% of girls' parents reported a provider recommendation to begin vaccination by 11-12 y old. Among unvaccinated teens, parental intention to vaccinate in the next 12 months did not differ by sex, but reasons for vaccination or non-vaccination did. Many parents do not know the recommended number of HPV doses. CONCLUSIONS: Gender differences in provider vaccination recommendations and reasons for vaccination might partially explain differential HPV uptake by male and female adolescents. Clinicians should offer strong recommendations for HPV vaccination at 11-12 y old for both girls and boys. To reduce missed opportunities, HPV vaccination should be presented in the context of, and given concurrently with, other routinely administered vaccines. PMID- 27003110 TI - 1,1-Hydroboration of Fused Azole-Isoindole Analogues as an Approach for Construction of B,N-Heterocycles and Azole-Fused B,N-Naphthalenes. AB - Three isoelectronic analogues of pyrido[2,1-a]isoindole have been found to undergo a facile 1,1-hydroboration with HBMes2 borane, which provides a new and convenient method for the synthesis of B,N-heterocycles 1a-3a in high yields. Compounds 1a-3a can undergo photoelimination upon irradiation at 300 nm, generating heterocycle-fused B,N-naphthalene molecules 1b-3b, which display distinct yellow-green and blue fluorescent colors, respectively. Compound 1a undergoes thermal elimination, producing 1b at 280 degrees C, while compound 2a only undergoes partial elimination, forming 2b at 320 degrees C. Compound 3a is thermally stable up to 320 degrees C. PMID- 27003111 TI - Three-Minute All-Out Test in Swimming. AB - PURPOSE: To validate the 3-minute all-out exercise test (3MT) protocol against the traditional critical-speed (CS) model (CSM) in front-crawl swimming. METHODS: Ten healthy swimmers or triathletes (mean +/- SD age 35.2 +/- 10.5 y, height 176.5 +/- 5.4 cm, body mass 69.6 +/- 8.2 kg) completed 5 tests (3MT, 100m, 200m, 400m, 800m) over 2 wk on separate days. Traditional CS and anaerobic distance capacity (D') were determined for each of the 3 traditional CSMs (linear distance time, LIN; linear speed/time, INV; nonlinear time-speed, NLIN) from the 4 set distance time trials. For the 3MT, CS was determined as the mean speed during the final 30 s of the test and D' was estimated as the power-time integral above the CS. RESULTS: Our results indicated no significant difference between the CS estimates determined from the traditional CSM and 3MT except for the INV model (P = .0311). Correlations between traditional CSMs and 3MT were high (r = .95, P < .01) However, D' differed and post hoc analysis indicated that D' estimated from 3MT was significantly lower than LIN (P = .0052) and NLIN (P < .0001). Correlations were weak (r < .55, P > .1). In addition, Bland-Altman plots between the traditional CSMs and 3MT CS estimates showed scattered points above and below the zero line, suggesting there is no consistent bias of one approach versus the other. CONCLUSIONS: The 3MT is a valid protocol for swimming to estimate CS. The demonstrated concurrent validity of the 3MT may allow more widespread use of CSMs to evaluate participants and responses to training. PMID- 27003112 TI - Correlation of visceral adipose tissue measured by Lunar Prodigy dual X-ray absorptiometry with MRI and CT in older men. AB - Quantification of abdominal visceral adipose tissue (VAT) is important to understand obesity-related comorbidities. We hypothesized that dual X-ray absorptiometry (DXA) measurements of VAT would correlate with traditional gold standards of magnetic resonance imaging (MRI) and computed tomography (CT) in older men. Deming regression and Bland-Altman plots were used to assess the agreement between VAT measured simultaneously by DXA and MRI (n=95) in a cohort of older males participating in a randomized trial of testosterone replacement for diabetes. We also correlated DXA with single-slice CT (n=102) in a cohort of older males undergoing testosterone deprivation for prostate cancer. Lunar Prodigy DXA scanners using enCORE software was used to measure VAT. DXA VAT volume strongly correlated with MRI VAT volume (r=0.90, P<0.0001) and CT VAT area (r=0.83, P<0.0001). As DXA assesses VAT volume in a smaller compartment than MRI, Bland-Altman analysis demonstrated DXA systematically underestimated VAT by an approximately 30% proportional bias. DXA VAT volume measured by Lunar Prodigy DXA scanners correlate well with gold standard MRI and CT quantification methods, and provides a low radiation, efficient, cost-effective option. Future clinical studies examining the effects of interventions on body composition and regional fat distribution may find DXA an appropriate volumetric method to quantify VAT. PMID- 27003113 TI - Anti-B7-H3 monoclonal antibody ameliorates the damage of acute experimental pancreatitis by attenuating the inflammatory response. AB - B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l-arginine-induced acute experimental pancreatitis. Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF kappaB signaling pathway, and ameliorated the pancreas disruption in l-arginine induced pancreatitis. In addition, although l-arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells, administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response. PMID- 27003114 TI - l-arginine and docetaxel synergistically enhance anti-tumor immunity by modifying the immune status of tumor-bearing mice. AB - l-arginine (l-Arg) supplementation has been reported to enhance the function of immune cells, including dendritic cells (DCs) and T lymphocytes, in cancer models thereby countering the suppressive effects of myeloid-derived suppressor cells (MDSCs). The balance of the active immune cells is one factor that determines the progression of cancers in vivo. Docetaxel (DTX), an immunomodulatory chemotherapeutic agent, is now widely used in several types of malignancies including breast cancer. We hypothesized that the combination of DTX and l-Arg would elicit a more robust antitumor response than either molecule alone. To test this hypothesis we utilized BALB/c mice inoculated with 4T1 mammary carcinoma cells. DTX and l-Arg synergistically limited tumor growth in vivo and moderately increased the life span of tumor bearing mice. The anti-tumor effects were associated with the proliferation of splenic CD8(+) CTL and CD4(+) Th1 effector cells, as well as increased serum levels of interferon gamma. More importantly, DTX+l-Arg effectively increased anti-tumor immunity within the tumor microenvironment. Furthermore, the combined therapy increased the number of myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, potent activators of the T cell response, and enhanced expression of the maturation markers CD86 and MHC II (required for antigen presentation). The combination therapy also reduced the proliferation of MDSCs. These data suggest that DTX+l-Arg may be a novel therapeutic strategy for breast cancer patients. PMID- 27003115 TI - The role of medial prefrontal corticosterone and dopamine in the antidepressant like effect of exercise. AB - Despite the well-documented beneficial effect of exercise on stress coping and depression treatment, its underlying neurobiological mechanism remains unclear. This is further complicated by a 'side effect' of exercise: it increases basal glucocorticoid (CORT), the stress hormone, which has been shown to be a mediator linking stress to depressive disorders. Here we show that three weeks of voluntary wheel running reduced rats' immobility in the forced swim test (FST), an antidepressant-like effect. Monitoring extracellular fluids in the medial prefrontal cortex PFC (mPFC) using microdialysis we found that, wheel running was associated with higher baseline CORT, but lower FST-responsive CORT. Further, wheel running resulted in a higher dopamine (DA) both at baseline and following FST. Interestingly, the antidepressant-like effect of wheel running was completely abolished by intra-mPFC pre-microinjection of a D2R (haloperidol) but not D1R (SCH23390) antagonist, at a dose that does not affect normal rats' performance in the FST. It suggests that exercise exerts antidepressant-like effect through upregulated DA and in a D2R dependent way in the mPFC. Importantly, the antidepressant-like effect of wheel running was also abolished by intra-mPFC pre-microinjection of a GR antagonist (RU486). Finally, intra-mPFC pre-microinjection of RU486 also downregulated the originally elevated basal and FST-responsive DA in the mPFC of exercise rats. These results suggest a causal pathway linking CORT, GR, DA, and D2R, to the antidepressant-like effect of exercise. In conclusion, exercise achieves antidepressant-like effect through the CORT-GR-DA-D2R pathway and that the increased basal CORT by exercise itself may be beneficial rather than detrimental. PMID- 27003116 TI - Learning to cope with stress modulates anterior cingulate cortex stargazin expression in monkeys and mice. AB - Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping with gains in subsequent emotion regulation. Here we investigate the effects of learning to cope with stress on anterior cingulate cortex gene expression in monkeys and mice. Anterior cingulate cortex is involved in learning, memory, cognitive control, and emotion regulation. Monkeys and mice were randomized to either stress coping or no-stress treatment conditions. Profiles of gene expression were acquired with HumanHT-12v4.0 Expression BeadChip arrays adapted for monkeys. Three genes identified in monkeys by arrays were then assessed in mice by quantitative real-time polymerase chain reaction. Expression of a key gene (PEMT) involved in acetylcholine biosynthesis was increased in monkeys by coping but this result was not verified in mice. Another gene (SPRY2) that encodes a negative regulator of neurotrophic factor signaling was decreased in monkeys by coping but this result was only partly verified in mice. The CACNG2 gene that encodes stargazin (also called TARP gamma-2) was increased by coping in monkeys as well as mice randomized to coping with or without subsequent behavioral tests of emotionality. As evidence of coping effects distinct from repeated stress exposures per se, increased stargazin expression induced by coping correlated with diminished emotionality in mice. Stargazin modulates glutamate receptor signaling and plays a role in synaptic plasticity. Molecular mechanisms of synaptic plasticity that mediate learning and memory in the context of coping with stress may provide novel targets for new treatments of disorders in human mental health. PMID- 27003117 TI - Changes in hippocampal volume and neuron number co-occur with memory decline in old homing pigeons (Columba livia). AB - The mammalian hippocampus is particularly susceptible to age-related structural changes, which have been used to explain, in part, age-related memory decline. These changes are generally characterized by atrophy (e.g., a decrease in volume and number of synaptic contacts). Recent studies have reported age-related spatial memory deficits in older pigeons similar to those seen in older mammals. However, to date, little is known about any co-occurring changes in the aging avian hippocampal formation (HF). In the current study, it was found that the HF of older pigeons was actually larger and contained more neurons than the HF of younger pigeons, a finding that suggests that the pattern of structural changes during aging in the avian HF is different from that seen in the mammalian hippocampus. A working hypothesis for relating the observed structural changes with spatial-cognitive decline is offered. PMID- 27003118 TI - Strain commonalities and differences in response-outcome decision making in mice. AB - The ability to select between actions that are more vs. less likely to be reinforced is necessary for survival and navigation of a changing environment. A task termed "response-outcome contingency degradation" can be used in the laboratory to determine whether rodents behave according to such goal-directed response strategies. In one iteration of this task, rodents are trained to perform two food-reinforced behaviors, then the predictive relationship between one instrumental response and the associated outcome is modified by providing the reinforcer associated with that response non-contingently. During a subsequent probe test, animals can select between the two trained responses. Preferential engagement of the behavior most likely to be reinforced is considered goal directed, while non-selective responding is considered a failure in response outcome conditioning, or "habitual." This test has largely been used with rats, and less so with mice. Here we compiled data collected from several cohorts of mice tested in our lab between 2012 and 2015. Mice were bred on either a C57BL/6 or predominantly BALB/c strain background. We report that both strains of mice can use information acquired as a result of instrumental contingency degradation training to select amongst multiple response options the response most likely to be reinforced. Mice differ, however, during the training sessions when the familiar response-outcome contingency is being violated. BALB/c mice readily generate perseverative or habit-like response strategies when the only available response is unlikely to be reinforced, while C57BL/6 mice more readily inhibit responding. These findings provide evidence of strain differences in response strategies when an anticipated reinforcer is unlikely to be delivered. PMID- 27003119 TI - Microextraction by packed sorbent (MEPS)-UHPLC-UV: A simple and efficient method for the determination of five benzodiazepines in an alcoholic beverage. AB - This article describes a nano-scale method for the determination and quantification of five benzodiazepines (BDZ) in an alcoholic grappa drink (chlordiazepoxide; lorazepam; diazepam; oxazepam; medazepam). BDZ are typically used in drug-facilitated crimes (DFC) for their accessibility and synergistic effects with alcohol. Specimens collected on the crime scene must be rapidly analyzed to prove the crime, though, in most cases, a very small amount is available. Off-line MEPS extraction of diluted grappa samples proved to be an efficient and reliable method for the recovery of the selected compounds. Requiring a very small amount of extraction solvents, MEPS is an environment friendly technique. LC separation with UV detection was used as the analytical technique because it is simple, robust, relatively economic and easy-to-find in most laboratories. The method was validated in terms of precision, accuracy and recovery. Limits of detection and quantitation were in the range of 0.5-2ng/MUL. Linearity (R(2)) spanned from 0.9994 and 1.0000. Intra- and inter-day repeatabilities were lower than 12% at any concentration. Recovery percentages of an equivalent-to-real sample at three different concentrations were between 70.7 and 74.1%. PMID- 27003120 TI - Rapid determination of recent cocaine use with magnetic particles-based enzyme immunoassays in serum, saliva, and urine fluids. AB - Cocaine is one of the most worldwide used illicit drugs. We report a magnetic particles-based enzyme-linked immunoassay (mpEIA) method for the rapid and sensitive determination of cocaine (COC) in saliva, urine and serum samples. Under optimized conditions, the limits of detections were 0.09ngmL(-1) (urine), 0.15ngmL(-1) (saliva), and 0.06ngmL(-1) COC (human serum). Sensitivities were in the range EC50=0.6-2.5ngmL(-1) COC. The cross-reactivity with the principal metabolite benzoylecgonine (BZE) was only 1.6%. Recovering percentages of doped samples (0, 10, 50, and 100ngmL(-1) of COC) ranged from about 86-111%. Some advantages of the developed mpEIA over conventional ELISA kits are faster incubations, improved reproducibility, and consumption of lower amounts of antibody and enzyme conjugates due to the use of magnetic beads. The reported method was validated following the guidelines on bioanalytical methods of the European Medicines Agency (2011). Unmetabolized COC detection has a great interest in pharmacological, pharmacokinetics, and toxicokinetics studies, and can be used to detect a very recent COC use (1-6h). PMID- 27003121 TI - Generation and characterization of a unique panel of anti-adalimumab specific antibodies and their application in therapeutic drug monitoring assays. AB - A number of assays are currently available to support therapeutic drug monitoring of adalimumab. A complete characterization of the assays and comparison of different assays has not been performed. The aim of this study, therefore, is to generate and characterize of a panel of monoclonal antibodies towards adalimumab (MA-ADM); to use this panel to develop novel assays to determine adalimumab concentrations; to assess the impact of tumor necrosis factor (TNF) and (non )neutralizing antibodies on adalimumab detection and to compare the performance of assays. In total, ten specific MA-ADM were generated of which four revealed a neutralizing potency of >78%. At least six different clusters were identified using principal component analysis. MA-ADM40D8 was selected as detecting antibody to determine adalimumab in the TNF-coated ELISA (A) and the MA-ADM28B8/MA-ADM40D8 antibody pair was chosen for use in the MA-coated ELISA (B). The impact of TNF and (non-) neutralizing antibodies was similar in both ELISAs. Finally, serum samples of adalimumab-treated Crohn's disease patients were collected and used for an external validation using the assay of Sanquin (C) and the apDia kit (D). All adalimumab assays showed excellent Pearson correlation: r=0.96 for A versus B, 0.96 for A versus C, 0.94 for A versus D, 0.97 for B versus C, 0.95 for B versus D and 0.94 for C and D. The excellent agreement with the two commercially available ELISAs allows harmonization of treatment algorithms in and between different hospitals/infusion centers. PMID- 27003122 TI - Identification and characterization of in vitro and in vivo generated metabolites of the adiponectin receptor agonists AdipoRon and 112254. AB - Peroxisome proliferator-activated receptors (PPARs), peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha), sirtuin 1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK) are regulators of transcriptional processes and effects of exercise and pseudo-exercise situations. Compounds occasionally referred to as endurance exercise mimetics such as AdipoRon and 112254, both adiponectin receptor agonists, can be used to simulate the physiology of endurance exercise via pathways including these transcriptional regulators. Adiponectin supports fatty acid utilization and triglyceride-content reduction in cells and increases both the mitochondrial biogenesis and the oxidative metabolism in muscle cells. In routine doping control analysis, knowledge about phase-I and -II metabolic products of target analytes is essential. Hence, in vitro- and in vivo-metabolism experiments are frequently employed tools in preventive doping research to determine potential urinary metabolites for sports drug testing purposes, especially concerning new, (yet) unapproved compounds. In the present study, in vitro assays were conducted using human liver microsomal and S9 fractions, and rat in vivo experiments were performed using both AdipoRon and 112254. For AdipoRon, obtained samples were analyzed using liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry with both electrospray ionization or atmospheric-pressure chemical ionization techniques. Overall, more than five phase I-metabolites were found in vitro and in vivo, including particularly monohydroxylated and hydrogenated species. No phase II-metabolites were found in vitro; conversely, signals suggesting the presence of glucuronic acid or other conjugates in samples collected from in vivo experiment were observed, the structures of which were however not conclusively identified. Also for 112254, several phase-I metabolites were found in vitro, e.g. monohydroxylated and demethylated species. Here, no phase II-metabolites were observed neither using in vitro nor in vivo samples. Based on the generated data, the implementation of metabolites and unmodified drug candidates into routine doping control protocols is deemed warranted for comprehensive sports drug testing programs until human elimination study data are available. PMID- 27003123 TI - Teriflunomide for multiple sclerosis. AB - BACKGROUND: This is an update of the Cochrane review "Teriflunomide for multiple sclerosis" (first published in The Cochrane Library 2012, Issue 12).Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system. It is clinically characterized by recurrent relapses or progression, or both, often leading to severe neurological disability and a serious decline in quality of life. Disease-modifying therapies (DMTs) for MS aim to prevent occurrence of relapses and disability progression. Teriflunomide is a pyrimidine synthesis inhibitor approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as a DMT for adults with relapsing remitting MS (RRMS). OBJECTIVES: To assess the absolute and comparative effectiveness and safety of teriflunomide as monotherapy or combination therapy versus placebo or other disease-modifying drugs (DMDs) (interferon beta (IFNbeta), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, dimethyl fumarate, alemtuzumab) for modifying the disease course in people with MS. SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Specialised Trials Register (30 September 2015). We checked reference lists of published reviews and retrieved articles and searched reports (2004 to September 2015) from the MS societies in Europe and America. We also communicated with investigators participating in trials of teriflunomide and the pharmaceutical company, Sanofi-Aventis. SELECTION CRITERIA: We included randomized, controlled, parallel-group clinical trials with a length of follow-up of one year or greater evaluating teriflunomide, as monotherapy or combination therapy, versus placebo or other approved DMDs for people with MS without restrictions regarding dose, administration frequency and duration of treatment. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures of Cochrane. Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among the review authors. We contacted the principal investigators of included studies for additional data or confirmation of data. MAIN RESULTS: Five studies involving 3231 people evaluated the efficacy and safety of teriflunomide 7 mg and 14 mg, alone or with add-on IFNbeta, versus placebo or IFNbeta-1a for adults with relapsing forms of MS and an entry Expanded Disability Status Scale score of less than 5.5.Overall, there were obvious clinical heterogeneities due to diversities in study designs or interventions and methodological heterogeneities across studies. All studies had a high risk of detection bias for relapse assessment and a high risk of bias due to conflicts of interest. Among them, three studies additionally had a high risk of attrition bias due to a high dropout rate and two studies had an unclear risk of attrition bias. The studies of combination therapy with IFNbeta (650 participants) and the study with IFNbeta-1a as controls (324 participants) also had a high risk for performance bias and a lack of power due to the limited sample.Two studies evaluated the benefit and the safety of teriflunomide as monotherapy versus placebo over a period of one year (1169 participants) or two years (1088 participants). A meta-analysis was not conducted. Compared to placebo, administration of teriflunomide at a dose of 7 mg/day or 14 mg/day as monotherapy reduced the number of participants with at least one relapse over one year (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.59 to 0.87, P value = 0.001 with 7 mg/day and RR 0.60, 95% CI 0.48 to 0.75, P value < 0.00001 with 14 mg/day) or two years (RR 0.85, 95% CI 0.74 to 0.98, P value = 0.03 with 7 mg/day and RR 0.80, 95% CI 0.69 to 0.93, P value = 0.004 with 14 days). Only teriflunomide at a dose of 14 mg/day reduced the number of participants with disability progression over one year (RR 0.55, 95% CI 0.36 to 0.84, P value = 0.006) or two years (RR 0.74, 95% CI 0.56 to 0.96, P value = 0.02). When taking the effect of drop-outs into consideration, the likely-case scenario analyses still showed a benefit in reducing the number of participants with at least one relapse, but not for the number of participants with disability progression. Both doses also reduced the annualized relapse rate and the number of gadolinium-enhancing T1-weighted lesions over two years. Quality of evidence for relapse outcomes at one year or at two years was low, while for disability progression at one year or at two years was very low.When compared to IFNbeta-1a, teriflunomide at a dose of 14 mg/day had a similar efficacy to IFNbeta-1a in reducing the proportion of participants with at least one relapse over one year, while teriflunomide at a dose of 7 mg/day was inferior to IFNbeta-1a (RR 1.52, 95% CI 0.87 to 2.67, P value = 0.14; 215 participants with 14 mg/day and RR 2.74, 95% CI 1.66 to 4.53, P value < 0.0001; 213 participants with 7 mg/day). However, the quality of evidence was very low.In terms of safety profile, the most common adverse events associated with teriflunomide were diarrhoea, nausea, hair thinning, elevated alanine aminotransferase, neutropenia and lymphopenia. These adverse events had a dose-related effects and rarely led to treatment discontinuation. AUTHORS' CONCLUSIONS: There was low-quality evidence to support that teriflunomide at a dose of 7 mg/day or 14 mg/day as monotherapy reduces both the number of participants with at least one relapse and the annualized relapse rate over one year or two years of treatment in comparison with placebo. Only teriflunomide at a dose of 14 mg/day reduced the number of participants with disability progression and delayed the progression of disability over one year or two years, but the quality of the evidence was very low. The quality of available data was too low to evaluate the benefit teriflunomide as monotherapy versus IFNbeta-1a or as combination therapy with IFNbeta. The common adverse effects were diarrhoea, nausea, hair thinning, elevated alanine aminotransferase, neutropenia and lymphopenia. These adverse effects were mostly mild-to-moderate in severity, but had a dose-related effect. New studies of high quality and longer follow-up are needed to evaluate the comparative benefit of teriflunomide on these outcomes and the safety in comparison with other DMTs. PMID- 27003124 TI - Small for gestational age and exposure to particulate air pollution in the early life environment of twins. AB - Several studies in singletons have shown that maternal exposure to ambient air pollutants is associated with restricted fetal growth. About half of twins have low birth weight compared with six percent in singletons. So far, no studies have investigated maternal air pollution exposure in association with birth weight and small for gestational age in twins. We examined 4760 twins of the East Flanders Prospective Twins Survey (2002-2013), to study the association between in utero exposure to air pollution with birth weight and small for gestational age. Maternal particulate air pollution (PM10) and nitric dioxide (NO2) exposure was estimated using a spatial temporal interpolation method over various time windows during pregnancy. In the total group of twins, we observed that higher PM10 and NO2 exposure during the third trimester was significantly associated with a lower birth weight and higher risk of small for gestational age. However, the association was driven by moderate to late preterm twins (32-36 weeks of gestation). In these twins born between 32 and 36 weeks of gestation, birth weight decreased by 40.2g (95% CI: -69.0 to -11.3; p=0.006) and by 27.3g (95% CI: -52.9 to -1.7; p=0.04) in association for each 10ug/m3 increment in PM10 and NO2 concentration during the third trimester. The corresponding odds ratio for small for gestational age were 1.68 (95% CI: 1.27-2.33; p=0.0003) and 1.51 (95% CI: 1.18-1.95; p=0.001) for PM10 or NO2, respectively. No associations between air pollution and birth weight or small for gestational age were observed among term born twins. Finally, in all twins, we found that for each 10ug/m3 increase in PM10 during the last month of pregnancy the within-pair birth weight difference increased by 19.6g (95% CI: 3.7-35.4; p=0.02). Assuming causality, an achievement of a 10ug/m3 decrease of particulate air pollution may account for a reduction by 40% in small for gestational age, in twins born moderate to late preterm. PMID- 27003125 TI - Marine sponge cyclic peptide theonellamide A disrupts lipid bilayer integrity without forming distinct membrane pores. AB - Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides derived from the marine sponge Theonella sp. These peptides specifically bind to 3beta-hydroxysterols, resulting in 1,3-beta-D-glucan overproduction and membrane damage in yeasts. The inclusion of cholesterol or ergosterol in phosphatidylcholine membranes significantly enhanced the membrane affinity of theonellamide A (TNM-A) because of its direct interaction with 3beta-hydroxyl groups of sterols. To better understand TNM-induced membrane alterations, we investigated the effects of TNM-A on liposome morphology. (31)P nuclear magnetic resonance (NMR) and dynamic light scattering (DLS) measurements revealed that the premixing of TNM-A with lipids induced smaller vesicle formation. When giant unilamellar vesicles were incubated with exogenously added TNM-A, confocal micrographs showed dynamic changes in membrane morphology, which were more frequently observed in cholesterol-containing than sterol-free liposomes. In conjunction with our previous data, these results suggest that the membrane action of TNM-A proceeds in two steps: 1) TNM-A binds to the membrane surface through direct interaction with sterols and 2) accumulated TNM-A modifies the local membrane curvature in a concentration-dependent manner, resulting in dramatic membrane morphological changes and membrane disruption. PMID- 27003126 TI - Role of charged lipids in membrane structures - Insight given by simulations. AB - Lipids and proteins are the main components of cell membranes. It is becoming increasingly clear that lipids, in addition to providing an environment for proteins to work in, are in many cases also able to modulate the structure and function of those proteins. Particularly charged lipids such as phosphatidylinositols and phosphatidylserines are involved in several examples of such effects. Molecular dynamics simulations have proved an invaluable tool in exploring these aspects. This so-called computational microscope can provide both complementing explanations for the experimental results and guide experiments to fruitful directions. In this paper, we review studies that have utilized molecular dynamics simulations to unravel the roles of charged lipids in membrane structures. We focus on lipids as active constituents of the membranes, affecting both general membrane properties as well as non-lipid membrane components, mainly proteins. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 27003127 TI - On the physiological/pathological link between Abeta peptide, cholesterol, calcium ions and membrane deformation: A molecular dynamics study. AB - The dynamic interplay between cholesterol, asymmetrically (at physiological condition) or symmetrically (hallmark of aging) distributed in membrane, and beta amyloid peptides is investigated by a computational approach. The drawn overall picture, starting from the very appearance of beta amyloid peptides and going through their self-assembling into potentially toxic oligomeric species, reinforces some of the experimental and theoretical shots recently reported in literature, while new important molecular hints on the physiological role played by the beta amyloid peptide are proposed. The so dreaded formation of amyloid pores selective for the passage of calcium ions could in fact explain their physiological concomitant recruitment in the regulation of synaptic plasticity. PMID- 27003129 TI - Freezing-induced uptake of trehalose into mammalian cells facilitates cryopreservation. AB - The aim of this study was to investigate if membrane-impermeable molecules are taken up by fibroblasts when exposing the cells to membrane phase transitions and/or freezing-induced osmotic forces. The membrane-impermeable fluorescent dye lucifer yellow (LY) was used to visualize and quantify uptake during endocytosis, and after freezing-thawing. In addition, trehalose uptake after freezing and thawing was studied. Fourier transform infrared spectroscopic studies showed that fibroblasts display a minor non-cooperative phase transition during cooling at suprazero temperatures, whereas cells display strong highly cooperative fluid-to gel membrane phase transitions during freezing, both in the absence and presence of protectants. Cells do not show uptake of LY upon passing the suprazero membrane phase transition at 30-10 degrees C, whereas after freezing and thawing cells show intracellular LY equally distributed within the cell. Both, LY and trehalose are taken up by fibroblasts after freezing and thawing with loading efficiencies approaching 50%. When using 250 mM extracellular trehalose during cryopreservation, intracellular concentrations greater than 100 mM were determined after thawing. A plot of cryosurvival versus the cooling rate showed a narrow inverted-'U'-shaped curve with an optimal cooling rate of 40 degrees C min(-1). Diluting cells cryopreserved with trehalose in isotonic cell culture medium resulted in a loss of cell viability, which was attributed to intracellular trehalose causing an osmotic imbalance. Taken together, mammalian cells can be loaded with membrane-impermeable compounds, including the protective agent trehalose, by subjecting the cells to freezing-induced osmotic stress. PMID- 27003128 TI - Enthalpy-driven interactions with sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides. AB - The first step of cell membrane penetration of arginine peptides is thought to occur via electrostatic interactions between positive charges of arginine residues and negative charges of sulfated glycosaminoglycans (GAGs) on the cell surface. However, the molecular interaction of arginine peptides with GAG still remains unclear. Here, we compared the interactions of several arginine peptides of Tat, R8, and Rev and their analogues with heparin in relation to the cell membrane penetration efficiency. The high-affinity binding of arginine peptides to heparin was shown to be driven by large favorable enthalpy contributions, possibly reflecting multidentate hydrogen bondings of arginine residues with sulfate groups of heparin. Interestingly, the lysine peptides in which all arginine residues are substituted with lysine residues exhibited negligible binding enthalpy despite of their considerable binding to heparin. In CHO-K1 cells, arginine peptides exhibited a great cell-penetrating ability whereas their corresponding lysine peptides did not penetrate into cells. The degree of cell penetration of arginine peptides markedly decreased by the chlorate treatment of cells which prevents the sulfation of GAG chains. Significantly, the cell penetration efficiency of arginine peptides was found to be correlated with the favorable enthalpy of binding to heparin. These results suggest that the enthalpy driven strong interaction with sulfated GAGs such as heparan sulfate plays a critical role in the efficient cell membrane penetration of arginine peptides. PMID- 27003130 TI - Genetics: modes of reproduction and genetic analysis. AB - Classical and reverse genetics remain invaluable tools for the scientific investigation of model organisms. Genetic analysis of endoparasites is generally difficult because the sexual adults required for crossing and other manipulations are usually hidden within their host. Strongyloides spp. and Parastrongyloides spp. are notable exceptions to this and their free-living adults offer unique opportunities to manipulate these parasites experimentally. Here I review the modes of inheritance in the two generations of Strongyloides/Parastrongyloides and I discuss the opportunities and the limitations of the currently available methodology for the genetic analysis of these two genera. PMID- 27003131 TI - Expression of fibroblast growth factor 21 in patients with biliary atresia. AB - Fibroblast growth factor 21 is a critical circulating adipokine involving in metabolic disorders and various liver diseases. This study was performed to investigate whether FGF21 is also associated with the pathophysiology of biliary atresia. Serum FGF21 levels were measured in 57 BA patients and 20 age matched healthy controls. We also examined hepatic FGF21 mRNA expression and FGF21 protein levels in liver tissues obtained from 15 BA patients undergoing liver transplantation and 5 cases of pediatric donation after cardiac death donor without liver diseases by RT-PCR and Western blotting. Patients with BA showed significantly higher serum FGF21 levels than those without BA (554.7pg/mL [83 2300] vs. 124.5pg/mL [66-270], P<0.05). Patients with BA also had significantly higher FGF21 mRNA and protein levels in hepatic tissues than control subjects. Serum FGF21 expression increased corresponding to the severity of liver fibrosis. Furthermore, serum FGF21 levels dropped significantly in BA patients within 6months after liver transplantation and approached baseline in healthy controls (P>0.05). In vivo, FXR knockout could significantly abrogate cholestasis induced FGF21 expression. FGF21 levels in serum and liver tissue increased significantly in BA patients. In vivo, cholestasis could induce FGF21 expression in FXR dependent manner. PMID- 27003132 TI - Evaluation of diagnostic performance of whole-body simultaneous PET/MRI in pediatric lymphoma. AB - BACKGROUND: Whole-body (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard of care for lymphoma. Simultaneous PET/MRI (magnetic resonance imaging) is a promising new modality that combines the metabolic information of PET with superior soft-tissue resolution and functional imaging capabilities of MRI while decreasing radiation dose. There is limited information on the clinical performance of PET/MRI in the pediatric setting. OBJECTIVE: This study evaluated the feasibility, dosimetry, and qualitative and quantitative diagnostic performance of simultaneous whole body FDG-PET/MRI in children with lymphoma compared to PET/CT. MATERIALS AND METHODS: Children with lymphoma undergoing standard of care FDG-PET/CT were prospectively recruited for PET/MRI performed immediately after the PET/CT. Images were evaluated for quality, lesion detection and anatomical localization of FDG uptake. Maximum and mean standardized uptake values (SUVmax/mean) of normal organs and SUVmax of the most FDG-avid lesions were measured for PET/MRI and PET/CT. Estimation of radiation exposure was calculated using specific age related factors. RESULTS: Nine PET/MRI scans were performed in eight patients (mean age: 15.3 years). The mean time interval between PET/CT and PET/MRI was 51 +/- 10 min. Both the PET/CT and PET/MRI exams had good image quality and alignment with complete (9/9) concordance in response assessment. The SUVs from PET/MRI and PET/CT were highly correlated for normal organs (SUVmean r(2): 0.88, P<0.0001) and very highly for FDG-avid lesions (SUVmax r(2): 0.94, P=0.0002). PET/MRI demonstrated an average percent radiation exposure reduction of 39% +/- 13% compared with PET/CT. CONCLUSION: Simultaneous whole-body PET/MRI is clinically feasible in pediatric lymphoma. PET/MRI performance is comparable to PET/CT for lesion detection and SUV measurements. Replacement of PET/CT with PET/MRI can significantly decrease radiation dose from diagnostic imaging in children. PMID- 27003133 TI - Posteromedial subtalar coalitions: prevalence and associated morphological alterations of the sustentaculum tali. AB - BACKGROUND: A variant form of subtalar coalition isolated to the posterior sustentaculum has been previously described, though its prevalence is not known and its relationship to the middle facet has not been characterized. OBJECTIVE: To determine the prevalence and morphological alterations of isolated posteromedial subtalar coalitions. MATERIALS AND METHODS: Computed tomography (CT) images of the foot or ankle performed from 2004 to 2012 were reviewed and 97 patients (mean age: 13.3+/-2.9 years; range: 9-19 years) with subtalar coalition were identified. In 41 (42%) of these, the condition was bilateral, yielding a total of 138 subtalar coalitions. In the 33 patients where CT demonstrated isolated posteromedial subtalar coalitions, multiplanar reformats along the long axis of the sustentaculum tali were generated, from which the anteroposterior dimensions of the sustentaculum tali and middle facet were measured. Posterior sustentaculum measurements defining the posterior extension of the sustentaculum beyond the middle facet were directly measured by two radiologists. Ratios of middle facet to posterior sustentaculum measurements were calculated. Thirty three patients undergoing CT for ankle fracture served as controls. RESULTS: Ninety-seven of 138 coalitions (70.2%) affected the middle facet and 2/138 (1.4%) involved the posterior facet. There were 39 (28.2%) posteromedial subtalar coalitions in 33 patients. Mean AP measurements of the middle facet and posterior sustentaculum in patients with posteromedial subtalar coalitions were 12.6 mm and 18.2 mm, respectively, compared to 16.6 mm and 9.2 mm in controls (P<0.001). Mean middle facet/posterior sustenaculum (MF/PS) ratios were 0.74 for posteromedial subtalar coalitions vs. 1.92 for controls (P<0.001). CONCLUSION: Posteromedial subtalar coalitions comprise more than one-quarter of subtalar coalitions, and are associated with an intact, but shorter, middle facet and longer sustentaculum tali. This observation may aid in accurate diagnosis and management of this relatively common disorder. PMID- 27003134 TI - Ultrasound of the duodenum in children. AB - Ultrasound is well suited for examining the pediatric duodenum, given the small size of the patients, the lack of ionizing radiation and high-resolution imaging potential. Technical considerations, normal anatomy, congenital and acquired pathology of the duodenum, and the advantages and limitations of US are discussed and illustrated in this review. PMID- 27003135 TI - Evaluation of single right atrial volume and function with magnetic resonance imaging in children with hypoplastic left heart. AB - BACKGROUND: Standardized methods to evaluate atrial properties in single ventricles are lacking. OBJECTIVE: To determine the feasibility of quantifying right atrial volumes and function in hypoplastic left heart using MRI. MATERIALS AND METHODS: We studied 15 infants with hypoplastic left heart prior to Glenn surgery (mean age 4.2 months [standard deviation 0.3]) who underwent cardiac MRI with evaluation of atrial volumes and emptying fraction using monoplane two chamber, monoplane four-chamber, and biplane methods, all of which were compared to the atrial short-axial oblique stack method. We compared atrial end-diastolic volume, end-systolic volume and emptying fraction among these methods. We analyzed reproducibility of the methods using Bland-Altman plots. RESULTS: Both four-chamber and biplane methods showed high correlations for atrial end diastolic volume (r = 0.7 and r = 0.8, respectively; P < 0.01) and end-systolic volume (r = 0.8 and r = 0.9, respectively; P < 0.01) with small mean differences (-0.2 +/- 2.9 standard deviation [SD] ml and -0.8 +/- 1.6 ml, respectively, for atrial end-diastolic volume and -0.8 +/- 1.5 ml and -0.9 +/- 0.9 ml, respectively, for atrial end-systolic volume). The short-axial oblique method was the most reproducible, followed by the four-chamber method. CONCLUSION: MRI assessment of atrial volume and function is feasible in hypoplastic left heart and might provide further insight into single-ventricle mechanics. PMID- 27003136 TI - Intimate Partner Violence in the Great Recession. AB - In the United States, the Great Recession was marked by severe negative shocks to labor market conditions. In this study, we combine longitudinal data from the Fragile Families and Child Wellbeing Study with U.S. Bureau of Labor Statistics data on local area unemployment rates to examine the relationship between adverse labor market conditions and mothers' experiences of abusive behavior between 2001 and 2010. Unemployment and economic hardship at the household level were positively related to abusive behavior. Further, rapid increases in the unemployment rate increased men's controlling behavior toward romantic partners even after we adjust for unemployment and economic distress at the household level. We interpret these findings as demonstrating that the uncertainty and anticipatory anxiety that go along with sudden macroeconomic downturns have negative effects on relationship quality, above and beyond the effects of job loss and material hardship. PMID- 27003137 TI - A Supervisor-Targeted Implementation Approach to Promote System Change: The R3 Model. AB - Opportunities to evaluate strategies to create system-wide change in the child welfare system (CWS) and the resulting public health impact are rare. Leveraging a real-world, system-initiated effort to infuse the use of evidence-based principles throughout a CWS workforce, a pilot of the R3 model and supervisor targeted implementation approach is described. The development of R3 and its associated fidelity monitoring was a collaboration between the CWS and model developers. Outcomes demonstrate implementation feasibility, strong fidelity scale measurement properties, improved supervisor fidelity over time, and the acceptability and perception of positive change by agency leadership. The value of system-initiated collaborations is discussed. PMID- 27003138 TI - A retrospective, semi-quantitative image quality analysis of cone beam computed tomography (CBCT) and MSCT in the diagnosis of distal radius fractures. AB - OBJECTIVE: To compare image quality and diagnostic validity of CBCT and MSCT for distal radius fractures. METHODS: 35 CBCT and 33 MSCT scans were retrospectively reviewed with a visual grading scale regarding the depiction of cortical bone, trabecular bone, articular surfaces, and soft tissue. The extent and type of artefacts was analyzed. Agreement on AO classification and measurement of cortical disruption and length of the fracture gap was determined. Fracture reduction was evaluated in post-treatment x-rays. Statistical analysis was performed with visual grading characteristics (VGC), chi square tests, and Kendall's coefficient of concordance. RESULTS: CBCT performed significantly worse for cortical bone, articular surfaces, and especially soft tissue. Trabecular bone showed no significant difference. Significantly more CBCT images showed artefacts. Physics-based artefacts were the most common. CBCT scans also showed motion artefacts. There was no significant difference in agreement on AO classification. The agreement on measurements was substantial for both modalities. Slightly more fractures that had undergone MSCT imaging showed adequate reduction. CONCLUSION: This initial study of an orthopaedic extremity CBCT scanner showed that the image quality of a CBCT scanner remains inferior for most structures at standard settings. Diagnostic validity of both modalities for distal radius fractures seems similar. KEY POINTS: * Subjectively, CBCT remains inferior to MSCT in depicting most structures. * Similar diagnostic validity for CBCT and MSCT imaging of distal radius fractures. * CBCT is a possible alternative to MSCT in musculoskeletal imaging. * Visual grading characteristics (VGC) analysis proves useful in analyzing visual grading scales. PMID- 27003139 TI - Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion- and perfusion-weighted imaging. AB - OBJECTIVES: To investigate whether amide proton transfer (APT) MR imaging can differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) among gliomas without intense contrast enhancement (CE). METHODS: This retrospective study evaluated 34 patients (22 males, 12 females; age 36.0 +/- 11.3 years) including 20 with LGGs and 14 with HGGs, all scanned on a 3T MR scanner. Only tumours without intense CE were included. Two neuroradiologists independently performed histogram analyses to measure the 90th-percentile (APT90) and mean (APTmean) of the tumours' APT signals. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were also measured. The parameters were compared between the groups with Student's t-test. Diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis. RESULTS: The APT90 (2.80 +/- 0.59 % in LGGs, 3.72 +/- 0.89 in HGGs, P = 0.001) and APTmean (1.87 +/- 0.49 % in LGGs, 2.70 +/- 0.58 in HGGs, P = 0.0001) were significantly larger in the HGGs compared to the LGGs. The ADC and rCBV values were not significantly different between the groups. Both the APT90 and APTmean showed medium diagnostic performance in this discrimination. CONCLUSIONS: APT imaging is useful in discriminating HGGs from LGGs among diffuse gliomas without intense CE. KEY POINTS: * Amide proton transfer (APT) imaging helps in grading non-enhancing gliomas * High-grade gliomas showed higher APT signal than low-grade gliomas * APT imaging showed better diagnostic performance than diffusion- and perfusion weighted imaging. PMID- 27003140 TI - Repeatability of derived parameters from histograms following non-Gaussian diffusion modelling of diffusion-weighted imaging in a paediatric oncological cohort. AB - OBJECTIVES: To examine repeatability of parameters derived from non-Gaussian diffusion models in data acquired in children with solid tumours. METHODS: Paediatric patients (<16 years, n = 17) were scanned twice, 24 h apart, using DWI (6 b-values, 0-1000 mm-2 s) at 1.5 T in a prospective study. Tumour ROIs were drawn (3 slices) and all data fitted using IVIM, stretched exponential, and kurtosis models; percentage coefficients of variation (CV) calculated for each parameter at all ROI histogram centiles, including the medians. RESULTS: The values for ADC, D, DDCalpha, alpha, and DDCK gave CV < 10 % down to the 5th centile, with sharp CV increases below 5th and above 95th centile. K, f, and D* showed increased CV (>30 %) over the histogram. ADC, D, DDCalpha, and DDCK were strongly correlated (rho > 0.9), DDCalpha and alpha were not correlated (rho = 0.083). CONCLUSION: Perfusion- and kurtosis-related parameters displayed larger, more variable CV across the histogram, indicating observed clinical changes outside of D/DDC in these models should be interpreted with caution. Centiles below 5th for all parameters show high CV and are unreliable as diffusion metrics. The stretched exponential model behaved well for both DDCalpha and alpha, making it a strong candidate for modelling multiple-b-value diffusion imaging data. KEY POINTS: * ADC has good repeatability as low 5th centile of the histogram distribution. * High CV was observed for all parameters at extremes of histogram. * Parameters from the stretched exponential model showed low coefficients of variation. * The median ADC, D, DDC alpha , and DDC K are highly correlated and repeatable. * Perfusion/kurtosis parameters showed high CV variations across their histogram distributions. PMID- 27003141 TI - Interpersonal psychotherapy (IPT) for major depression following perinatal loss: a pilot randomized controlled trial. AB - This randomized controlled pilot trial examined the feasibility, acceptability, and preliminary efficacy of an adapted interpersonal psychotherapy (IPT) for major depressive disorder (MDD) following perinatal loss (miscarriage, stillbirth, or early neonatal death). Fifty women who experienced a perinatal loss within the past 18 months, whose current depressive episode onset occurred during or after the loss, were randomized to the group IPT adapted for perinatal loss (the Group IPT for Major Depression Following Perinatal Loss manual developed for this study is available at no cost by contacting either of the first two authors) or to the group Coping with Depression (CWD), a cognitive behavioral treatment which did not focus on perinatal loss nor social support. Assessments occurred at baseline, treatment weeks 4 and 8, post-treatment, and 3 and 6 months after the end of treatment. IPT was feasible and acceptable in this population. Although some participants were initially hesitant to discuss their losses in a group (as occurred in IPT but not CWD), end of treatment satisfaction scores were significantly (p = 0.001) higher in IPT than in CWD. Confidence intervals around between-groups effect sizes favored IPT for reductions in depressive symptoms during treatment as well as for improvement in mode-specific targets (social support, grief symptoms) and recovery from a post-traumatic stress disorder over follow-up. This group IPT treatment adapted for MDD after perinatal loss is feasible, acceptable, and possibly efficacious. PMID- 27003142 TI - Natural History of Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) remains among the most common liver diseases worldwide, with increasing prevalence in concert with the obesity and metabolic syndrome epidemic. The evidence on the natural history, albeit with some ambiguity, suggests the potential for some subsets of NAFLD to progress to cirrhosis, liver-related complications and mortality with fibrosis being the most important predictor of hard long-term endpoints such as mortality and liver complications. In this setting, NAFLD proves to be a formidable disease entity, with considerable clinical burden, for both the present and the future. Our understanding of the natural history of NAFLD is constantly evolving, with nascent data challenging current dogma. Further clarification of the natural history is required with well-designed, well-defined studies using prospectively collected data. Identifying the predictors of long-term outcomes should be used to direct development of clinical trial endpoints in NAFLD. PMID- 27003143 TI - Novel Pharmacotherapy Options for NASH. AB - While simple to recommend, diet and lifestyle measures as a first-line therapy for nonalcoholic steatohepatitis (NASH) are hardly a model of successful therapy, as most clinicians can testify. They can be complex to implement, hard to sustain, and of limited efficacy in advanced stages of the disease. The need for specific pharmacotherapy is now acknowledged by practitioners, the pharmaceutical industry, and regulators and is largely expected by patients. The result is a clear move away from products developed second hand for NASH (such as pioglitazone or metformin) or from generic, non-specific hepatoprotectors (such as pentoxifylline, ursodeoxycholic acid, or antioxidants) toward molecules developed and tested specifically for NASH that aim to correct one or several of the pathways of liver injury in this disease. The two most advanced molecules, obeticholic acid and elafibranor, have shown encouraging data on improving hepatic histology. Both compounds appear to clear NASH, with obeticholic acid improving liver fibrosis and elafibranor improving the glycemic and lipid profile. Much larger trials, currently ongoing, will need to confirm these preliminary data and better characterize the safety and tolerability profile. Meanwhile, other compounds are being tested, a few in phase 2b studies (cenicriviroc, aramchol for NASH, and simtuzumab for NASH fibrosis) and many more in earlier, smaller trials. Most of these drug candidates target different pathways, which speaks to the diversity and dynamism of the NASH pipeline. PMID- 27003144 TI - Overview of High-Risk Medical Device Innovation in Gastroenterology from 2000 to 2014: Enhancing the Pipeline. AB - Medical devices are a critical component in the diagnosis and treatment of diseases of the alimentary tract. The United States Food and Drug Administration database was mined for high-risk medical device development via the pre-market approval (PMA) pathway from 2000 to 2014. In total, there were only nine GI (gastrointestinal) devices approved during this period. Furthermore, only one GI device was granted expedited review. The clinical studies leading to approval were mostly limited to non-blinded, non-randomized studies. Only a minority of pivotal studies defined and met their primary endpoints (27 %). Eight out of nine devices were required to undergo post-marketing studies. Ultimately, cardiology led with 157 total approvals in the time period studied. GI ranked 12 out of 18 across various medical and surgical specialties and accounted for <2 % of total PMA approvals. Future efforts should focus on spurring more high-risk device innovation in the field. PMID- 27003145 TI - Comparison of Performance Characteristics of Oval Cup Forceps Versus Serrated Jaw Forceps in Gastric Biopsy. AB - BACKGROUND: Obtaining quality endoscopic biopsy specimens is vital in making successful histological diagnoses. The influence of forceps cup shape and size on quality of biopsy specimens is unclear. AIM: To identify whether oval cup or two different serrated jaw biopsy forceps could obtain specimens of superior size. Secondary endpoints were tissue adequacy, depth of tissue acquisition, and crush artifact. METHODS: A single-center, prospective, pathologist-masked, randomized controlled trial was performed. In total 136 patients with a clinical indication for esophagogastroduodenoscopy with biopsy were randomized to receive serial biopsies with a large-capacity serrated forceps with jaw diameter 2.2 mm (SER1) and either a large-capacity oval forceps with jaw diameter 2.4 mm (OVL) or large capacity serrated biopsy forceps with jaw diameter 2.4 mm (SER2) in two parallel groups. RESULTS: SER2 provided significantly larger specimens than did the other forceps (SER2 3.26 +/- 1.09 vs. SER1 2.92 +/- 0.88 vs. OVL 2.92 +/- 0.76; p = 0.026), with an average size difference of 0.34 mm greater with SER2 compared to SER1 and OVL. OVL provided significantly deeper biopsies compared to SER1 and SER2 (p = 0.02), with 31 % of OVL biopsies reaching the submucosa. SER2 had significantly less crush artifact than SER1 and OVL (p < 0.0001). CONCLUSION: Serrated forceps provided larger samples compared to oval jaw forceps of the same size, with SER2 providing the largest specimen size. Oval cup forceps had deeper penetration of epithelium, while the larger jaw diameter serrated jaw forceps had less crush artifact. All three forceps provided specimens adequate for diagnostic purposes. PMID- 27003147 TI - Fecal Microbiota Transplantation for Ulcerative Colitis: FoMenTing Change? PMID- 27003148 TI - Evaluation of cochlear nerve diameter and cross-sectional area in ANSD patients by 3.0-Tesla MRI. AB - CONCLUSIONS: The size of cochlear nerve (CN) is atrophic in adult auditory neuropathy spectrum disorder (ANSD) patients compared with non-ANSD sensorineural hearing loss (SNHL) patients and normal hearing subjects, and CN deficiency is one of the lesions for ANSD patients. OBJECTIVES: To evaluate the dimensions of CN in adult ANSD patients on magnetic resonance imaging (MRI) and confirm the hypothesis that CN deficiency is one of the lesions for ANSD patients. METHODS: Medical records and MRI of 24 adult ANSD patients reviewed retrospectively and 20 non-ANSD SNHL and 24 volunteers with normal hearing were recruited as control groups. The long diameter (LD), short diameter (SD), and cross-sectional area (CSA) of CN and facial nerve (FN) were measured. RESULTS: Among the 24 ANSD patients, this study was able to reconstruct and measure the CN of 91.7% (22/24, total 43 ears) of patients and FN of 83.3% (20/24, total 38 ears) of patients. The mean values and standard deviations of LD, SD, and CSA of CN in ANSD patients were 0.65 +/- 0.20 mm, 0.44 +/- 0.15 mm, and 0.30 +/- 0.19 mm(2), respectively. They were significantly smaller in ANSD patients than in control groups (p < 0.001). PMID- 27003146 TI - Amoxicillin-Clavulanate-Induced Liver Injury. AB - BACKGROUND AND AIMS: Amoxicillin-clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC DILI to those of other drugs. METHODS: Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. RESULTS: One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. CONCLUSION: AC-DILI causes a moderately severe, mixed hepatocellular-cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation. PMID- 27003149 TI - Biodegradable biliary stents have a different effect than covered metal stents on the expression of proteins associated with tissue healing in benign biliary strictures. AB - BACKGROUND: Benign biliary strictures (BBS) are primarily treated endoscopically with covered self-expandable metal stents (CSEMS). Biodegradable biliary stents (BDBS) may be the future of endoscopic therapy of BBS. The aim was to assess the expression of proteins related to tissue healing in BBS compared with the intact bile duct (BD), and to study the protein expression after therapy with CSEMS or BDBS. METHODS: Pigs with ischemic BBS were endoscopically treated either with BDBS or CSEMS. Samples were harvested from pigs with intact BD (n = 5), untreated BBS (n = 5), and after six months of therapy with BDBS (n = 4) or CSEMS (n = 5) with subsequent histologic analysis. Two-dimensional electrophoresis with protein identification was performed to evaluate protein expression patterns. RESULTS: In BBS, the expression of galectin-2 and annexin-A4 decreased, compared to intact BD. Treatment with biodegradable stents normalized galectin-2 level; with CSEMS therapy it remained low. Transgelin expression of intact BD and BBS remained low after BDBS treatment but increased after CSEMS therapy. Histologic analysis did not show unwanted foreign body reaction or hyperplasia in the BD in either group. CONCLUSIONS: The expression of proteins related to tissue healing in BBS is different after treatment with biodegradable stents and CSEMS. Treatment with biodegradable stents may bring protein expression towards what is seen in intact BD. BDBS seem to have a good biocompatibility. PMID- 27003151 TI - Assessing Rates of Inadequate Feeding Practices Among Children 12-24 months: Results from a Cross-Sectional Survey in Myanmar. AB - Objectives To ensure proper nutrition and optimal health outcomes, it is critical that infants are exclusively breastfed (0-6 months) and then receive adequate feeding from 6-23 months (breastfeeding and frequent feedings of complementary foods). Despite policies and guidelines on adequate feeding in Myanmar, past research has found low rates of adequately fed infants 0-11 months and little is known about the adequacy of feeding practices for children 12-23 months. The aim of this study is to understand the feeding practices of children aged 0-24 months in Myanmar and maternal characteristics associated with adequate feeding practices. Methods This study examines the rates of adequately fed infants and young children (0-23 months) in hard-to-reach townships in Myanmar from a cross sectional, multistage cluster survey. Survey data on nutritional practices were collected from 489 mothers. Data were analyzed using multivariate regressions. Results We found that 41.8 % of infants under 6 months were exclusively breastfed, 63.2 % of those aged 6-11 months were adequately fed, and 10.3 % of 12 23 month-olds were adequately fed. In multivariate regressions we found that antenatal care visits [1-4 visits, AOR = 6.59 (p < 0.01) and >4 visits, AOR = 6.63 (p < 0.05)] was associated with exclusive breastfeeding for under 6 month old infants. Having >4 antenatal care visits [AOR = 9.97 (p < 0.05)] was associated with adequate feeding for 6-11 months old infants. Conclusions Future nutritional interventions and policies should focus on improving messaging about adequate feeding practices, especially for 12-23 months olds. PMID- 27003150 TI - Gestational Weight Gain, Body Mass Index, and Risk of Hypertensive Disorders of Pregnancy in a Predominantly Puerto Rican Population. AB - Objectives To prospectively evaluate the association between gestational weight gain (GWG), prepregnancy body mass index (BMI), and hypertensive disorders of pregnancy using the revised Institute of Medicine (IOM) Guidelines. Methods We examined these associations among 1359 participants in Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011 among women from the Caribbean Islands. Information on prepregnancy BMI, GWG, and incident diagnoses of hypertension in pregnancy were based on medical record abstraction. Results Four percent (n = 54) of women were diagnosed with hypertension in pregnancy, including 2.6 % (n = 36) with preeclampsia. As compared to women who gained within IOM GWG guidelines (22.8 %), those who gained above guidelines (52.5 %) had an odds ratio of 3.82 for hypertensive disorders (95 % CI 1.46-10.00; ptrend = 0.003) and an odds ratio of 2.94 for preeclampsia (95 % CI 1.00-8.71, ptrend = 0.03) after adjusting for important risk factors. Each one standard deviation (0.45 lbs/week) increase in rate of GWG was associated with a 1.74 odds of total hypertensive disorders (95 % CI 1.34-2.27) and 1.86 odds of preeclampsia (95 % CI 1.37-2.52). Conclusions for Practice Findings from this prospective study suggest that excessive GWG is associated with hypertension in pregnancy and could be a potentially modifiable risk factor in this high-risk ethnic group. PMID- 27003152 TI - Latina and Non-Latina Mothers' Perceived Health Barriers and Benefits and Their Relationship to Children's Health Behaviors. AB - Objectives Disparities exist in rates of overweight/obesity between Latino and non-Latino populations. Attention should be given to risk factors that may be modifiable through interventions involving both the parent and child. The current study sought to identify ethnic differences in parental health beliefs and their relation to children's health behaviors. Methods Latina and non-Latina mothers (N = 203) at rural and urban clinics and health departments completed self-report questionnaires. Key information included beliefs about barriers and benefits to health practices and children's health behaviors. Results Children of Latina mothers consumed significantly more soda and fried foods and exercised less than children of non-Latina mothers. Latina mothers were significantly more likely to perceive barriers to healthy eating and significantly less likely to perceive benefits to healthy eating and physical activity than non-Latina mothers. Ethnicity mediated the relationship between maternal views of health benefits and soda consumption. Conclusions Policy changes are needed to promote health education and increase the accessibility of healthy foods and safe places to exercise for Latino families. PMID- 27003153 TI - Abdominal aortic calcification in patients with CKD. AB - BACKGROUND: Abdominal aortic calcification (AAC) is independently associated with cardiovascular events in dialysis patients and in the general population. However, data in non-dialysis chronic kidney disease (CKD) patients are limited. We analyzed determinants and prognostic value of AAC in non-dialysis CKD patients. METHODS: We included patients with CKD not receiving renal replacement therapy from the MASTERPLAN study, a randomized controlled trial that started in 2004. In the period 2008-2009, an X-ray to evaluate AAC was performed in a subgroup of patients. We studied AAC using a semi-quantitative scoring system by lateral lumbar X-ray. We used baseline and 2-year data to find determinants of AAC. We used a composite cardiovascular endpoint and propensity score matching to evaluate the prognostic value of AAC. RESULTS: In 280 patients an X-ray was performed. In 79 patients (28 %) the X-ray showed no calcification, in 62 patients (22 %) calcification was minor (<4), while 139 patients (50 %) had moderate or heavy calcification (>=4). Older age, prior cardiovascular disease, higher triglyceride levels, and higher phosphate levels were independent determinants of a calcification score >=4. AAC score >=4 was independently associated with cardiovascular events, with a hazard ratio of 5.5 (95 % confidence interval 1.2-24.8). CONCLUSIONS: Assessment of AAC can identify CKD patients at higher cardiovascular risk, and may provide important information for personalized treatment. Whether this approach will ultimately translate into better outcomes remains to be answered. PMID- 27003154 TI - Giant cell rich osteosarcoma revisited-diagnostic criteria and histopathologic patterns, Ki67, CDK4, and MDM2 expression, changes in response to bisphosphonate and denosumab treatment. AB - Defining giant cell-rich osteosarcoma (GCRO) as "an osteosarcoma in which more than 50% of the tumor consists of numerous uniformly distributed osteoclastic giant cells amidst oval or spindle mononuclear cells embedded in a fibrovascular stroma," eight such cases identified among 265 cases of osteosarcoma were analysed. Their age ranges from 11 to 33 years, with peak incidence in the second decade and equal sex distribution. Seventy-five percent presented with pain, commonest in the knee, affecting the metaphysis. Most appeared radiologically as well-circumscribed expansile multiloculated osteolytic lesions, and many are displayed periosteal reaction. They showed several distinct histologic patterns: the stromal and giant cell, fibrohistiocytic, aneurysmal-cystic, osteoblastoma like, and parosteal and fibrous dysplasia-like patterns. Focal subtle lacelike osteoid deposition, permeative infiltration into adjacent native bony trabeculae and over 30 % Ki67 proliferative index were characteristic. There was no CDK4 and MDM2 amplification. In those having bisphosphonate and denosumab treatment, there was limited focal necrosis with reduction in the number of giant cells and broad trabecular woven bone formation but no giant osteoclast was seen. Two patients with initial diagnosis of giant cell tumor treated by curettage and local resection pursued aggressive clinical courses, died after 14 and 21 months. The others survived 12 to 110 months. GCRO accounts for about 3 % of all osteosarcomas and apart from its more frequent diaphyseal location and associated normal bone-specific alkaline phosphate levels; it shares with conventional high grade osteosarcoma the same patient demographics, sites of occurrence, absence of CDK4 and MDM2 amplification, and probably clinical course. PMID- 27003155 TI - NGS-based BRCA1/2 mutation testing of high-grade serous ovarian cancer tissue: results and conclusions of the first international round robin trial. AB - With the approval of olaparib as monotherapy treatment in platinum-sensitive, relapsed high-grade serous ovarian cancer by the European Medical Agency (EMA), comprehensive genotyping of BRCA1 and BRCA2 in tumor tissue has become a mandatory pre-therapeutic test. This requires significant advances in routine tumor test methodologies due to the large size of both genes and the lack of mutational hot spots. Classical focused screening approaches, like Sanger sequencing, do not allow for a sensitive, rapid, and economic analysis of tumor tissue. Next-generation sequencing (NGS) approaches employing targeted panels for BRCA1/2 to interrogate formalin-fixed and paraffin-embedded tumor samples from either surgical resection or biopsy specimens can overcome these limitations. Although focused NGS methods have been implemented by few centers in routine molecular diagnostics for the analysis of some druggable oncogenic mutations, the reliable diagnostic testing of the entire coding regions of BRCA1 and BRCA2 was a new challenge requiring extensive technological improvement and quality management. Here, we describe the implementation and results of the first round robin trial for BRCA1/2 mutation testing in tumor tissue that was conducted in central Europe on May 2015, shortly after the approval and prior to the official release of olaparib. The high success rate of 81 % (21/26 test centers) demonstrates that BRCA1/2 multicenter mutation testing is well feasible in FFPE tumor tissue, extending to other tumor entities beyond ovarian cancer. The high number of test centers passing the trial demonstrates the success of the concerted efforts by German, Swiss, and Austrian pathology centers to ensure quality-controlled NGS-based testing and proves the potential of this technology in routine molecular pathology. On the basis of our results, we provide recommendations for predictive testing of tumor tissue for BRCA1/2 to clinical decision making in ovarian cancer patients. PMID- 27003156 TI - Serous tubal intraepithelial carcinoma, chronic fallopian tube injury, and serous carcinoma development. AB - Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p < 0.001). No differences in tubal injury or inflammation were seen when comparing the sporadic serous cancer group and the control group or within the hereditary group. STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified. PMID- 27003157 TI - Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors. AB - Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays. PMID- 27003158 TI - Loss of DAB2IP expression in human urothelial carcinoma is associated with poorer recurrence-free survival. AB - The purpose of this study is to investigate the clinical relevance of deletion of ovarian carcinoma 2/disabled homolog 2 (DOC-2/DAB2) interacting protein (DAB2IP) expression in human urothelial carcinoma (UC). We studied DAB2IP protein expression by immunohistochemistry in 130 UCs (90 of the bladder and 40 of the upper urinary tract) and 79 adjacent normal tissues and assessed its prognostic value in terms of recurrence-free and progression-free survival in superficial bladder UC. Twelve human UC cell lines were examined for DAB2IP messenger RNA (mRNA) and protein expression using quantitative RT-PCR and western blotting. Selected cell lines were used to study the effect of treatment with chromatin modifying agents (5-aza-2'-deoxycytidine, Trichostatin A, or both) on DAB2IP expression. Of 90 bladder tumors, 50 (56 %) and, of 40 upper tract UC, 11 (28 %) were positive for DAB2IP immunostaining (bladder cancer versus upper tract UC, p = 0.003). In 65 superficial cases of bladder cancer loss of DAB2IP, expression was significantly associated with decreased recurrence-free survival (p = 0.046), but not with progression-free survival. Most human urothelial cancer cell lines consistently express DAB2IP mRNA and protein, without any relation to S-phase kinase protein expression. After treatment with either 5-aza-2'-deoxycytidine or Trichostatin A or both, the low DAB2IP-expressing bladder cancer cell lines BFTC905 and BFTC909 showed increased DAB2IP mRNA expression. DAB2IP protein levels are higher in bladder cancer than in upper tract UC and in superficial bladder cancer. This is associated with longer recurrence-free survival. Epigenetic regulation of DAB2IP protein appears to play an important role in human urothelial carcinoma. PMID- 27003159 TI - Proteasome activators, PA28gamma and PA200, play indispensable roles in male fertility. AB - Protein degradation mediated by the proteasome is important for the protein homeostasis. Various proteasome activators, such as PA28 and PA200, regulate the proteasome function. Here we show double knockout (dKO) mice of Psme3 and Psme4 (genes for PA28gamma and PA200), but not each single knockout mice, are completely infertile in male. The dKO sperms exhibited remarkable defects in motility, although most of them showed normal appearance in morphology. The proteasome activity of the mutant sperms decreased notably, and the sperms were strongly positive with ubiquitin staining. Quantitative analyses of proteins expressed in dKO sperms revealed up-regulation of several proteins involved in oxidative stress response. Furthermore, increased 8-OHdG staining was observed in dKO sperms head, suggesting defective response to oxidative damage. This report verified PA28gamma and PA200 play indispensable roles in male fertility, and provides a novel insight into the role of proteasome activators in antioxidant response. PMID- 27003160 TI - The Burden of Drug-Resistant Tuberculosis in Papua New Guinea: Results of a Large Population-Based Survey. AB - BACKGROUND: Reliable estimates of the burden of multidrug-resistant tuberculosis (MDR-TB) are crucial for effective control and prevention of tuberculosis (TB). Papua New Guinea (PNG) is a high TB burden country with limited information on the magnitude of the MDR-TB problem. METHODS: A cross-sectional study was conducted in four PNG provinces: Madang, Morobe, National Capital District and Western Province. Patient sputum samples were tested for rifampicin resistance by the Xpert MTB/RIF assay and those showing the presence of resistance underwent phenotypic susceptibility testing to first- and second-line anti-TB drugs including streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, ofloxacin, amikacin, kanamycin and capreomycin. RESULTS: Among 1,182 TB patients enrolled in the study, MDR-TB was detected in 20 new (2.7%; 95% confidence intervals [CI] 1.1-4.3%) and 24 previously treated (19.1%; 95%CI: 8.5-29.8%) TB cases. No case of extensively drug-resistant TB (XDR-TB) was detected. Thirty percent (6/20) of new and 33.3% (8/24) of previously treated cases with MDR-TB were detected in a single cluster in Western Province. CONCLUSION: In PNG the proportion of MDR-TB in new cases is slightly lower than the regional average of 4.4% (95%CI: 2.6-6.3%). A large proportion of MDR-TB cases were identified from a single hospital in Western Province, suggesting that the prevalence of MDR-TB across the country is heterogeneous. Future surveys should further explore this finding. The survey also helped strengthening the use of smear microscopy and Xpert MTB/RIF testing as diagnostic tools for TB in the country. PMID- 27003161 TI - The Molecular Epidemiology of Resistance in Cefotaximase-Producing Escherichia coli Clinical Isolates from Dublin, Ireland. AB - In view of continued high clinical prevalence of infections involving extended spectrum beta-lactamase (ESBL)-producing Escherichia coli, this study sought to characterise the blaCTX-M genes, their associated mobile genetic elements and the integrons present in 100 ESBL-producing E. coli isolates collected in a Dublin hospital and associated community healthcare facilities. Polymerase chain reaction (PCR) mapping and sequencing was used to detect blaCTX-M alleles, their associated insertion sequences (ISs) and class 1 and 2 integrons in the collection. ESBL plasmids were characterised by PCR-based replicon typing and replicon sequence typing (RST). Cefotaximases were harboured by 94% of isolates (66 blaCTX-M-15, 8 blaCTX-M-14, 7 blaCTX-M-1, 4 blaCTX-M-3, 3 blaCTX-M-9, 2 blaCTX-M-27, 2 blaCTX-M-55, 1 blaCTX-M-32 and 1 blaCTX-M-2). An ISEcp1 promoter was linked to a group 1 blaCTX-M gene in 45% of isolates. A further 34% of isolates contained blaCTX-M-15 downstream of IS26, an arrangement typical of epidemic UK strain A. Class 1 integrons were found in 66% of isolates, most carrying trimethoprim/aminoglycoside resistance genes. CTX-M plasmids were primarily of multireplicon IncF or IncI1 type, but IncN and unidentified types were also found. Novel IncF RSTs F1:A-:B-, F45:A1:B-, F45:A4:B- and a novel IncI1 sequence type, ST159, were identified. CTX-M plasmids and integrons resembled those identified recently in animal isolates from Ireland and Western Europe. The molecular epidemiology of CTX-M-producing E. coli in Dublin suggests that horizontal spread of mobile genetic elements contributes to antimicrobial resistant human infections. Further investigations into whether animals or animal products represent an important local reservoir for these elements are warranted. PMID- 27003162 TI - Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection. AB - Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID- 27003164 TI - An In Vivo Study of Self-Regulated Study Sequencing in Introductory Psychology Courses. AB - Study sequence can have a profound influence on learning. In this study we investigated how students decide to sequence their study in a naturalistic context and whether their choices result in improved learning. In the study reported here, 2061 undergraduate students enrolled in an Introductory Psychology course completed an online homework tutorial on measures of central tendency, a topic relevant to an exam that counted towards their grades. One group of students was enabled to choose their own study sequence during the tutorial (Self Regulated group), while the other group of students studied the same materials in sequences chosen by other students (Yoked group). Students who chose their sequence of study showed a clear tendency to block their study by concept, and this tendency was positively associated with subsequent exam performance. In the Yoked group, study sequence had no effect on exam performance. These results suggest that despite findings that blocked study is maladaptive when assigned by an experimenter, it may actually be adaptive when chosen by the learner in a naturalistic context. PMID- 27003163 TI - Effects of a Gentle, Self-Administered Stimulation of Perineal Skin for Nocturia in Elderly Women: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial. AB - BACKGROUND: Somatic afferent nerve stimuli are used for treating an overactive bladder (OAB), a major cause of nocturia in the elderly. Clinical evidence for this treatment is insufficient because of the lack of appropriate control stimuli. Recent studies on anesthetized animals show that gentle stimuli applied to perineal skin with a roller could inhibit micturition contractions depending on the roller's surface material. We examined the efficacy of gentle skin stimuli for treating nocturia. METHODS: The study was a cross-over, placebo-controlled, double-blind randomized clinical study using two rollers with different effects on micturition contractions. Participants were elderly women (79-89 years) with nocturia. Active (soft elastomer roller) or placebo (hard polystyrene roller) stimuli were applied to perineal skin by participants for 1 min at bedtime. A 3 day baseline assessment period was followed by 3-day stimulation and 4-day resting periods, after which the participants were subjected to other stimuli for another 3 days. The primary outcome was change in the frequency of nighttime urination, for which charts were maintained during each 3-day period. RESULTS: Twenty-four participants were randomized, of which 22 completed all study protocols. One participant discontinued treatment because of an adverse event (abdominal discomfort). In participants with OAB (n = 9), change from baseline in the mean frequency of urination per night during the active stimuli period (mean +/- standard deviation, -0.74 +/- 0.7 times) was significantly greater than that during placebo stimuli periods (-0.15 +/- 0.8 times [p < 0.05]). In contrast, this difference was not observed in participants without OAB (n = 13). CONCLUSIONS: These results suggest that gentle perineal stimulation with an elastomer roller is effective for treating OAB-associated nocturia in elderly women. Here the limitation was a study period too short to assess changes in the quality of sleep and life. TRIAL REGISTRATION: UMIN Clinical Trial Registry (CTR) UMIN000015809. PMID- 27003165 TI - Prevalence and Antimicrobial Susceptibility of Mycobacterium abscessus in a General Hospital, China. AB - OBJECTIVE: To gain greater insight into the prevalence drug resistant profiles of M. abscessus from a general hospital in Beijing, China. METHODS: Partial gene sequencing of 16S, hsp65, and rpoB were used to distinguish the species of NTM isolates. All strains identified as M. abscessus were further enrolled in the drug susceptibility testing by using broth microdilution method. RESULTS: We found that M. avium complex was the most frequent NTM organism, accounting for 54.1% (33/61) of all isolates. Behind MAC, the second most common organisms were M. abscessus (22 out of 61, 36.1%). Average rates of resistance were 4.5% for AMK, 9.1% for LZD, and 13.6% for CLA, respectively. In contrast, resistance to LEV (17/22, 77.3%), IMI (9/22, 40.9%), and SMX (10/22, 45.5%) was noted in more than 40% of M. abscessus isolates. DNA sequencing revealed that all the CLA resistant isolates harbored nucleotide substitutions in position 2058 (1/3, 33.3%) or 2059 (2/3, 66.7%) of 23S rRNA. CONCLUSION: In conclusion, our data demonstrated that M. intracellulare and M. abscessus were the most common NTM species in the general hospital of Beijing. CLA, AMK, LZD showed promising activity, where as LEV, IMI, and SMX exhibited poor activity against M. abscessus in vitro. PMID- 27003166 TI - Prevalence and Risk Factors of Primary Drug-Resistant Tuberculosis in China. AB - OBJECTIVE: To investigate the prevalence of primary drug-resistant tuberculosis (TB) and associated risk factors in China. We also explored factors contributing to the transmission of multidrug-resistant tuberculosis (MDR-TB). METHODS: A total of 2794 representative, Mycobacterium tuberculosis isolates from treatment naive patients were subjected to drug susceptibility testing, and risk factors for drug-resistant TB were analyzed. We also analyzed MDR-TB strain sublineages, drug-resistance-conferring mutations, and risk factors associated with clustered primary MDR strains. RESULTS: Among 2794 Mycobacterium tuberculosis isolates from treatment-naive patients, the prevalence of any resistance to first-line drugs was 33.2% and the prevalence of MDR-TB was 5.7%. We did not find any risk factors significantly associated with resistance to first-line drugs. The 93 primary MDR TB isolates were classified into six sublineages, of which, 75 (80.6%) isolates were the RD105-deleted Beijing lineage. The largest sublineage included 65 (69.9%) isolates with concurrent deletions of RD105, RD207, and RD181. Twenty nine (31.2%) primary MDR strains grouped in clusters; MDR isolates in clusters were more likely to have S531L rpoB mutation. CONCLUSION: This study indicates that primary drug-resistant TB and MDR-TB strains are prevalent in China, and multiple measures should be taken to address drug-resistant TB. PMID- 27003167 TI - The Survey of Cronobacter spp. (formerly Enterbacter sakazakii) in Infant and Follow-up Powdered Formula in China in 2012. AB - OBJECTIVE: To determine Cronobacter spp. contamination in infant and follow-up powdered formula in China. METHODS: All of 2282 samples were collected from the retail markets in China from January 2012 to December 2012, and analyzed for Cronobacter spp. by the Chinese National Food Safety Standard. Characterization of the isolates was analyzed by pulsed-field gel electrophoresis (PFGE) with XbaI and SpeI restriction enzymes. RESULTS: Cronobacter spp. strains were isolated from 25 samples, and the positive rates in infant powdered formulas and follow-up powdered formulas were 0.90% (10/1011) and 1.18% (15/1271), respectively. Analysis of variable data regarding different purchasing store formats, seasonality, and production locations as well as comparison of infant versus follow-up formulas did not reveal statistically significant factors. During the sampling period, one of six surveillance zones did exhibit a statistically significant trend towards higher positive rate. PFGE characterization of Cronobacter spp. to elucidate genetic diversity revealed only three pairs of Cronobacter spp. out of 25 having the same PFGE patterns. CONCLUSION: The current investigation indicated a lower positive rate of Cronobacter spp. in the powdered formula in China. This evidence suggested contamination originating from multiple different sources during the manufacturing process. PMID- 27003168 TI - The Cellular Toxicity of PM2.5 Emitted from Coal Combustion in Human Umbilical Vein Endothelial Cells. AB - OBJECTIVE: To explore the relationship between different components of fine particulate matter (PM2.5) emitted from coal combustion and their cytotoxic effect in the vascular endothelial cells. METHODS: Coal-fired PM(2.5) was sampled using a fixed-source dilution channel and flow sampler. The sample components were analyzed by ion chromatography and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The PM(2.5) suspension was extracted using an ultrasonic water-bath method and then human umbilical vein endothelial cells (EA.hy926) were treated with various concentrations of the PM(2.5) suspension. Cell proliferation, oxidative DNA damage, and global DNA methylation levels were used to measure the cellular toxicity of PM(2.5) emitted from coal combustion. RESULTS: Compared to other types of coal-fired PM(2.5) preparations, the PM2.5 suspension from Yinchuan coal had the highest cytotoxicity. PM(2.5) suspension from Datong coal had the highest toxic effect while that from Yinchuan coal had the lowest. Exposure to coal-fired PM(2.5) from Jingxi coal resulted in lower 8 hydroxy-2'-deoxyguanosine (8-OHdG) levels. At the same dose, PM(2.5) emitted from coal combustion could produce more severe DNA impairment compared to that produced by carbon black. Cell survival rate was negatively correlated with chloride and potassium ions content. The 5-methylcytosine (5-mC) level was positively correlated with Mn and negatively correlated with Zn levels. The 8 OHdG% level was positively correlated with both Mn and Fe. CONCLUSION: PM(2.5) emitted from coal combustion can decrease cell viability, increase global DNA methylation, and cause oxidative DNA damage in EA.hy926 cells. Metal components may be important factors that influence cellular toxicity. PMID- 27003169 TI - Cadmium Activates Reactive Oxygen Species-dependent AKT/mTOR and Mitochondrial Apoptotic Pathways in Neuronal Cells. AB - OBJECTIVE: To examine the role of Cd-induced reactive oxygen species (ROS) generation in the apoptosis of neuronal cells. METHODS: Neuronal cells (primary rat cerebral cortical neurons and PC12 cells) were incubated with or without Cd post-pretreatment with rapamycin (Rap) or N-acetyl-L-cysteine (NAC). Cell viability was determined by MTT assay, apoptosis was examined using flow cytometry and fluorescence microscopy, and the activation of phosphoinositide 3' kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and mitochondrial apoptotic pathways were measured by western blotting or immunofluorescence assays. RESULTS: Cd-induced activation of Akt/mTOR signaling, including Akt, mTOR, p70 S6 kinase (p70 S6K), and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Rap, an mTOR inhibitor and NAC, a ROS scavenger, blocked Cd-induced activation of Akt/mTOR signaling and apoptosis of neuronal cells. Furthermore, NAC blocked the decrease of B-cell lymphoma 2/Bcl-2 associated X protein (Bcl-2/Bax) ratio, release of cytochrome c, cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G (Endo G). CONCLUSION: Cd induced ROS generation activates Akt/mTOR and mitochondrial pathways, leading to apoptosis of neuronal cells. Our findings suggest that mTOR inhibitors or antioxidants have potential for preventing Cd-induced neurodegenerative diseases. PMID- 27003170 TI - Bioremediation of Hexavalent Chromium Pollution by Sporosarcina saromensis M52 Isolated from Offshore Sediments in Xiamen, China. AB - OBJECTIVE: Cr(VI) removal from industrial effluents and sediments has attracted the attention of environmental researchers. In the present study, we aimed to isolate bacteria for Cr(VI) bioremediation from sediment samples and to optimize parameters of biodegradation. METHODS: Strains with the ability to tolerate Cr(VI) were obtained by serial dilution and spread plate methods and characterized by morphology, 16S rDNA identification, and phylogenetic analysis. Cr(VI) was determined using the 1,5-diphenylcarbazide method, and the optimum pH and temperature for degradation were studied using a multiple-factor mixed experimental design. Statistical analysis methods were used to analyze the results. RESULTS: Fifty-five strains were obtained, and one strain (Sporosarcina saromensis M52; patent application number: 201410819443.3) having the ability to tolerate 500 mg Cr(VI)/L was selected to optimize the degradation conditions. M52 was found be able to efficiently remove 50-200 mg Cr(VI)/L in 24 h, achieving the highest removal efficiency at pH 7.0-8.5 and 35 degrees C. Moreover, M52 could completely degrade 100 mg Cr(VI)/L at pH 8.0 and 35 degrees C in 24 h. The mechanism involved in the reduction of Cr(VI) was considered to be bioreduction rather than absorption. CONCLUSION: The strong degradation ability of S. saromensis M52 and its advantageous functional characteristics support the potential use of this organism for bioremediation of heavy metal pollution. PMID- 27003171 TI - Gene Knockdown in Human Rhinovirus 1B Using 2'-OMe-modified siRNAs Results in the Reactivation of the Interferon Response. AB - The aim of this study was to investigate the knockdown efficiency of 2'-O methylated (2'-OMe)-modified small interfering RNAs (siRNAs) on human rhinovirus 1B (HRV1B) replication and the interferon response. Thus, 24 2'-OMe-modified siRNAs were designed to target HRV1B. The RNA levels of HRV1B, Toll-like receptor 3, melanoma differentiation-associated gene 5, retinoic acid inducible gene-I, and interferons were determined in HRV1B-infected HeLa and BEAS-2B epithelial cells transfected with 2'-OMe-modified siRNAs. The results revealed that all 2' OMe-modified siRNAs interfered with the replication of HRV1B in a cell-specific and transfection efficiency-dependent manner. Viral activation of Toll-like receptor 3, melanoma differentiation-associated gene 5, retinoic acid inducible gene-I, and the interferon response was detected. In conclusion, the 2'-OMe modified siRNAs used in this study could interfere with HRV1B replication, possibly leading to the reactivation of the interferon response. PMID- 27003172 TI - Protective Effects of Lycopene on Furan-treated Diabetic and Non-diabetic Rat Lung. AB - We assessed the effects of furan and lycopene on the histopathological and biochemical changes on lungs, body and lung weights, and food consumption of rats. Furan and diabetes caused histopathological changes, increment in malondialdehyde levels, and decrease in antioxidant enzyme activities. Lycopene showed a protective effect against these damages, except for glutathione-S transferase and glutathione peroxidase activities. Consequently, furan and diabetes resulted in lung toxicity. Our findings demonstrate that furan treatment resulted in more alterations in histology and biochemical parameters in diabetic rats and lycopene showed protective effects against these alterations. PMID- 27003173 TI - Evaluation of Protective Effects of Bioactive Phytochemicals Against Methotrexate in Salmonella typhimurium TA1535/pSK1002 Coupled with Micronucleus Assay. AB - We evaluated the antimutagenic effects of 10 kinds of bioactive phytochemicals and some phytochemical combinations against methotrexate (MTX)-induced genotoxicity by the umu test in Salmonella typhimurium TA1535/pSK1002 combined with a micronucleus assay. We observed that allicin, proanthocyanidins, polyphenols, eleutherosides, and isoflavones had higher antimutagenic activities than the other five types of bioactive phytochemicals. At the highest dose tested, MTX-induced genotoxicity was inhibited by 25%-75%. Kunming mice treated by MTX along with bioactive phytochemical combinations showed significant reduction in micronucleus induction and sperm abnormality rate (P<0.01). These results indicate that bioactive phytochemical combinations can be potentially used as new cytoprotectors. PMID- 27003174 TI - Dimethylacetamide-induced Hepatic Injury in Vitro: Mechanism and Potential Preventive Strategy. AB - N,N-Dimethylacetamide (DMAc) is a widely used organic solvent in modern chemical industry with low to moderate hepatotoxicity to occupational health of employees. But so far, there are fewer and less conclusive data concerning its pathogenic mechanism in detail. In current study, the toxicity of DMAc was firstly investigated on human normal hepatocytes (LO-2), using a series of molecular biology measurements to ananlyze the effect and mechanism of DMAc-induced hepatic cell injury and explore effective prophylactic measures. We found that DMAc triggered LO-2 apoptosis in a obviously dose-dependent manner, caused by increased ROS generation and activation of Bcl-2 pathway. Significantly, glutathione (GSH) rather than vitamin C (Vit C) could partially inhibit DMAc induced apoptosis thus showing potential as a effective precaution for workers. PMID- 27003175 TI - Interleukin 8 Gene Polymorphisms Are Not Associated with Tuberculosis Susceptibility in the Chinese Population. AB - Interleukin 8 (IL8) is an important chemokine that elicits host immune response against tuberculosis (TB). However, whether there is an association between IL8 gene polymorphism and TB susceptibility in the Chinese population is unknown. IL8 gene was amplified and sequenced to search for nucleotide polymorphisms among the Chinese population. Four single nucleotide polymorphisms (SNPs) were identified, selected, and analyzed in a cohort of 438 patients with TB and 536 healthy controls. Allelic, genotypic, and haplotypic analysis demonstrated that the distribution of the four IL8 SNPs between patients with TB and healthy controls was not significantly different (P>0.05). The four IL8 SNPs detected in this study were not associated with TB susceptibility in the Chinese population. Secretion of IL8 by peripheral blood cells was greatly stimulated upon exposure to Mycobacterium tuberculosis whole cell extract, but such enhanced secretion was not associated with the IL8 rs4073 alleles. PMID- 27003176 TI - The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review. AB - OBJECTIVE: x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices. METHODS: In this work we review the literature discussing the findings from animal models to clinical studies focused on the neurobiological pathways of endogenous but mainly exogenous GHB. RESULTS: Chronic abuse of GHB exerts multifarious neurotransmitter and neuromodulator effects on x03B3; aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine and cholinergic systems. Moreover, important effects on neurosteroidogenesis and oxytocin release are wielded. GHB acts mainly via a bidirectional effect on GABAB receptors (GABABR; subunits GABAB1 and GABAB2), depending on the subunit of the GIRK (G-protein-dependent ion inwardly rectifying potassium) channel involved, and an indirect effect of the cortical and limbic inputs outside the nucleus accumbens. GHB also activates a specific GHB receptor and beta1-subunits of alpha4-GABAAR. Reversing this complex interaction of neurobiological mechanisms by the abrupt cessation of GHB use results in a withdrawal syndrome with a diversity of symptoms of different intensity, depending on the pattern of GHB abuse. CONCLUSION: The GHB withdrawal symptoms cannot be related to a single mechanism or neurological pathway, which implies that different medication combinations are needed for treatment. A single drug class, such as benzodiazepines, gabapentin or antipsychotics, is unlikely to be sufficient to avoid life-threatening complications. Detoxification by means of titration and tapering of pharmaceutical GHB can be considered as a promising treatment that could make polypharmacy redundant. PMID- 27003177 TI - Isoniazid toxicity and TB development during biological therapy of patients with psoriasis in Colombia. AB - Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 +/- 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up. PMID- 27003178 TI - Delivery of a drug cache to glioma cells overexpressing platelet-derived growth factor receptor using lipid nanocarriers. AB - AIM: Glioblastoma multiforme is a devastating disease with no curative options due to the difficulty in achieving sufficient quantities of effective chemotherapies into the tumor past the blood-brain barrier. Micelles loaded with temozolomide (TMZ) were designed to increase the delivery of this drug into the brain. MATERIALS & METHODS: pH-responsive micelles composed of distearoyl phosphoethanolamine-PEG-2000-amine and N-palmitoyl homocysteine were surface functionalized with PDGF peptide and Dylight 680 fluorophore. RESULTS & CONCLUSION: PDGF-micelles containing TMZ have specific uptake and increased killing in glial cells compared with untargeted micelles. In vivo studies demonstrated selective accumulation of PDGF-micelles containing TMZ in orthotopic gliomas implanted in mice. Targeted micelle-based drug carrier systems hold potential for delivery of a wide variety of hydrophobic drugs thereby reducing its systemic toxicity. PMID- 27003180 TI - Rice: The First Crop Genome. AB - Rice was the first sequenced crop genome, paving the way for the sequencing of additional and more complicated crop genomes. The impact that the genome sequence made on rice genetics and breeding research was immediate, as evidence by citations and DNA marker use. The impact on other crop genomes was evident too, particularly for those within the grass family. As we celebrate 10 years since the completion of the rice genome sequence, we look forward to new empowering tool sets that will further revolutionize research in rice genetics and breeding and result in varieties that will continue to feed a growing population. PMID- 27003179 TI - Multimodal MRI Evaluation of the MitoPark Mouse Model of Parkinson's Disease. AB - The MitoPark mouse, a relatively new genetic model of Parkinson's disease (PD), has a dopaminergic neuron-specific knock-out that inactivates the mitochondrial transcription factor A (Tfam), a protein essential for mitochondrial DNA expression and maintenance. This study used multimodal MRI to characterize the neuroanatomical correlates of PD-related deficits in MitoPark mice, along with functional behavioral tests. Compared with age-matched wild-type animals, MitoPark mice at 30 weeks showed: i) reduced whole-brain volume and increased ventricular volume, indicative of brain atrophy, ii) reduced transverse relaxation time (T2*) of the substantia nigra and striatum, suggestive of abnormal iron accumulation, iii) reduced apparent diffusion coefficient in the substantia nigra, suggestive of neuronal loss, iv) reduced fractional anisotropy in the corpus callosum and substantia nigra, indicative of white-matter damages, v) cerebral blood flow was not significantly affected, and vi) reduced motor activity in open-field tests, reduced memory in novel object recognition tests, as well as decreased mobility in tail suspension tests, an indication of depression. In sum, MitoPark mice recapitulate changes in many MRI parameters reported in PD patients. Multimodal MRI may prove useful for evaluating neuroanatomical correlates of PD pathophysiology in MitoPark mice, and for longitudinally monitoring disease progression and therapeutic interventions for PD. PMID- 27003181 TI - Role of Nuclear Medicine in the Diagnosis of Benign Thyroid Diseases. AB - A deep understanding of thyroid pathophysiology is the basis for diagnosing and treating benign thyroid diseases with radioactive materials, known as radiopharmaceuticals, which are introduced into the body by injection or orally. After the radiotracer administration, the patient becomes the emitting source, and several devices have been studied to detect and capture these emissions (gamma or beta-negative) and transform them into photons, parametric images, numbers and molecular information. Thyroid scintigraphy is the only technique that allows the assessment of thyroid regional function and, therefore, the detection of areas of autonomously functioning thyroid nodules. Scintigraphy visualizes the distribution of active thyroid tissue and displays the differential accumulation of radionuclides in the investigated cells, thus providing a functional map. Moreover, this technique is a fundamental tool in the clinical and surgical management of thyroid diseases, including: single thyroid nodules with a suppressed thyroid-stimulating hormone level, for which fine needle aspiration biopsy (FNAB) is used to identify hot nodules; multinodular goiters, especially larger ones, to identify cold or indeterminate areas requiring FNAB and hot areas that do not need cytologic evaluation, and to evaluate mediastinal extension; the diagnosis of ectopic thyroid tissue; subclinical hyperthyroidism to identify occult hyperfunctioning tissue; follicular lesions to identify a functioning cellular adenoma that could be benign, although such nodules are mostly cold on scintigraphy; to distinguish low uptake from high-uptake thyrotoxicosis, and to determine eligibility for radioiodine therapy. PMID- 27003182 TI - Embryonal Rhabdomyosarcoma of the Cervix in Young Women. AB - PURPOSE: Cervical rhabdomyosarcoma (RMS) is an extremely rare disease, and there is no precise criteria related to its treatment. Our aim was to describe the clinical and pathological features of cervical RMS. METHODS: Clinicopathological data of cases with cervical RMS were retrieved from the computerized database of Etlik Zubeyde Hanim Women's Health and Research Hospital. Five patients with the diagnosis of cervical RMS who underwent surgical treatment and had adjuvant chemotherapy between 2003 and 2015 were included in the study. RESULTS: Mean age of patients at the time of diagnosis was 15.8 +/- 2 years. Abnormal vaginal bleeding and mass were the most common complaints. All patients had embryonal rhabdomyosarcoma (E-RMS) and Group I disease according to the Intergroup Rhabdomyosarcoma Study Group clinical classification system. Cone biopsy and polypectomy were performed in four patients, and radical abdominal hysterectomy with pelvic-paraaortic lymphadenectomy was performed in one patient. Chemotherapy consisting vincristine, dactinomycin, and cyclophosphamide was given as an adjuvant therapy. Estimated 5-year overall survival and disease-free survival were 40% and 37.5%, respectively. CONCLUSIONS: We report a small series of patients with cervical E-RMS who were treated with surgery and adjuvant chemotherapy. Although all patients in the present study had good prognostic factors, survival was not as good as indicated in the literature. Diminished survival of our patient group may be associated with underlying molecular and pathophysiologic differences other than stage and histological subtype that have not been discovered yet. PMID- 27003183 TI - Evaluation of a two-part regression calibration to adjust for dietary exposure measurement error in the Cox proportional hazards model: A simulation study. AB - Dietary questionnaires are prone to measurement error, which bias the perceived association between dietary intake and risk of disease. Short-term measurements are required to adjust for the bias in the association. For foods that are not consumed daily, the short-term measurements are often characterized by excess zeroes. Via a simulation study, the performance of a two-part calibration model that was developed for a single-replicate study design was assessed by mimicking leafy vegetable intake reports from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. In part I of the fitted two part calibration model, a logistic distribution was assumed; in part II, a gamma distribution was assumed. The model was assessed with respect to the magnitude of the correlation between the consumption probability and the consumed amount (hereafter, cross-part correlation), the number and form of covariates in the calibration model, the percentage of zero response values, and the magnitude of the measurement error in the dietary intake. From the simulation study results, transforming the dietary variable in the regression calibration to an appropriate scale was found to be the most important factor for the model performance. Reducing the number of covariates in the model could be beneficial, but was not critical in large-sample studies. The performance was remarkably robust when fitting a one-part rather than a two-part model. The model performance was minimally affected by the cross-part correlation. PMID- 27003184 TI - Measurement of Myocardial T1rho with a Motion Corrected, Parametric Mapping Sequence in Humans. AB - PURPOSE: To develop a robust T1rho magnetic resonance imaging (MRI) sequence for assessment of myocardial disease in humans. MATERIALS AND METHODS: We developed a breath-held T1rho mapping method using a single-shot, T1rho-prepared balanced steady-state free-precession (bSSFP) sequence. The magnetization trajectory was simulated to identify sources of T1rho error. To limit motion artifacts, an optical flow-based image registration method was used to align T1rho images. The reproducibility and accuracy of these methods was assessed in phantoms and 10 healthy subjects. Results are shown in 1 patient with pre-ventricular contractions (PVCs), 1 patient with chronic myocardial infarction (MI) and 2 patients with hypertrophic cardiomyopathy (HCM). RESULTS: In phantoms, the mean bias was 1.0 +/- 2.7 msec (100 msec phantom) and 0.9 +/- 0.9 msec (60 msec phantom) at 60 bpm and 2.2 +/- 3.2 msec (100 msec) and 1.4 +/- 0.9 msec (60 msec) at 80 bpm. The coefficient of variation (COV) was 2.2 (100 msec) and 1.3 (60 msec) at 60 bpm and 2.6 (100 msec) and 1.4 (60 msec) at 80 bpm. Motion correction improved the alignment of T1rho images in subjects, as determined by the increase in Dice Score Coefficient (DSC) from 0.76 to 0.88. T1rho reproducibility was high (COV < 0.05, intra-class correlation coefficient (ICC) = 0.85-0.97). Mean myocardial T1rho value in healthy subjects was 63.5 +/- 4.6 msec. There was good correspondence between late-gadolinium enhanced (LGE) MRI and increased T1rho relaxation times in patients. CONCLUSION: Single-shot, motion corrected, spin echo, spin lock MRI permits 2D T1rho mapping in a breath-hold with good accuracy and precision. PMID- 27003185 TI - Do footfall patterns in forefoot runners change over an exhaustive run? AB - The purpose of this study was to investigate possible footfall pattern changes in habitual forefoot runners over a prolonged, exhaustive run. A prolonged run was performed to exhaustion in 14 habitual forefoot runners. Vertical ground reaction forces (VGRFs) and kinematics were collected at the beginning and end of the run. Ankle plantar flexor torque and triceps surae electromyographic activity were measured during pre- and post-run isometric contractions. By run's end, there was an increase in VGRF loading rate and impact peak magnitude, greater dorsiflexion at foot contact and greater knee flexion angle throughout stance. Ankle plantar flexor torque decreased significantly from pre- to post-run tests. This was accompanied by a decrease in the integrated electromyographic activity (iEMG) output for the lateral and medial gastrocnemius. There were significant changes in landing mechanics for forefoot runners that indicate a transition towards more midfoot footfall patterns. A contributing factor may be ankle plantar flexor muscle fatigue that, at touchdown, is exposed to exaggerated eccentric loading. These findings suggest that a forefoot running pattern may become difficult to maintain in longer endurance events, and thus runners should pay attention to this in training to improve performance and mitigate potential injury. PMID- 27003186 TI - Taurocholic acid metabolism by gut microbes and colon cancer. AB - Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively. PMID- 27003187 TI - Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures. AB - Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement. PMID- 27003188 TI - The effects of the dopamine stabilizer (-)-OSU6162 on aggressive and sexual behavior in rodents. AB - The dopamine stabilizer (-)-OSU61612 dampens locomotion in rodents rendered hyperactive by exposure to a novel environment or treatment with amphetamine, but stimulates locomotion in habituated animals displaying low motor activity, tentatively exerting this profile by selectively blocking extrasynaptic D2 receptors. The major aim of the present study was to explore the possible usefulness of (-)-OSU61612 as an anti-aggressive drug. To this end, the effect of (-)-OSU61612 on isolation-induced aggression in male mice and estrous cycle dependent aggression in female rats were studied using the resident intruder test; in addition, the possible influence of (-)-OSU61612 on sexual behavior in male mice and on elevated plus maze (EPM) performance in male rats were assessed. (-)-OSU61612 at doses influencing neither locomotion nor sexual activity reduced aggression in male mice. The effect was observed also in serotonin-depleted animals and is hence probably not caused by the antagonism of serotonin receptors displayed by the drug; refuting the possibility that it is due to 5-HT1B activation, it was also not counteracted by isamoltane. (-)-OSU61612 did not display the profile of an anxiogenic or anxiolytic drug in the EPM but caused a general reduction in activity that is well in line with the previous finding that it reduces exploratory behavior of non-habituated animals. In line with the observations in males, (-)-OSU61612 reduced estrus cycle-related aggression in female Wistar rats, a tentative animal model of premenstrual dysphoria. By stabilizing dopaminergic transmission, (-)-OSU61612 may prove useful as a well tolerated treatment of various forms of aggression and irritability. PMID- 27003191 TI - Trends in long-term opioid prescribing in primary care patients with musculoskeletal conditions: an observational database study. AB - Long-term opioids may benefit patients with chronic pain but have also been linked to harmful outcomes. In the United Kingdom, the predominant source of opioids is primary care prescription. The objective was to examine changes in the incidence, length, and opioid potency of long-term prescribing episodes for musculoskeletal conditions in UK primary care (2002-2013). This was an observational database study (Clinical Practice Research Datalink, 190 practices). Participants (>=18 years) were prescribed an opioid for a musculoskeletal condition (no opioid prescribed in previous 6 months), and issued >=2 opioid prescriptions within 90 days (long-term episode). Opioids were divided into short- and long-acting noncontrolled and controlled drugs. Annual incidence of long-term opioid episodes was determined, and for those still in a long-term episode, the percentage of patients prescribed each type 1 to 2 years, and >2 years after initiation. Annual denominator population varied from 1.25 to 1.38 m. A total of 76,416 patients started 1 long-term episode. Annual long-term episode incidence increased (2002-2009) by 38% (42.4-58.3 per 10,000 person-years), remaining stable to 2011, then decreasing slightly to 55.8/10,000 (2013). Patients prescribed long-acting controlled opioids within the first 90 days of long-term use increased from 2002 to 2013 (2.3%-9.9%). In those still in a long term opioid episode (>2 years), long-acting controlled opioid prescribing increased from 3.5% to 22.6%. This study has uniquely shown an increase in prescribing long-term opioids to 2009, gradually decreasing from 2011 in the United Kingdom. The trend was towards increased prescribing of controlled long acting opioids and earlier use. Further research into the risks and benefits of opioids is required. PMID- 27003192 TI - Age-related variance in decisions under ambiguity is explained by changes in reasoning, executive functions, and decision-making under risk. AB - Previous literature has explained older individuals' disadvantageous decision making under ambiguity in the Iowa Gambling Task (IGT) by reduced emotional warning signals preceding decisions. We argue that age-related reductions in IGT performance may also be explained by reductions in certain cognitive abilities (reasoning, executive functions). In 210 participants (18-86 years), we found that the age-related variance on IGT performance occurred only in the last 60 trials. The effect was mediated by cognitive abilities and their relation with decision-making performance under risk with explicit rules (Game of Dice Task). Thus, reductions in cognitive functions in older age may be associated with both a reduced ability to gain explicit insight into the rules of the ambiguous decision situation and with failure to choose the less risky options consequently after the rules have been understood explicitly. Previous literature may have underestimated the relevance of cognitive functions for age-related decline in decision-making performance under ambiguity. PMID- 27003189 TI - Functional magnetic resonance imaging in awake transgenic fragile X rats: evidence of dysregulation in reward processing in the mesolimbic/habenular neural circuit. AB - Anxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were 'odor naive' to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology. PMID- 27003193 TI - [Periprosthetic fractures]. PMID- 27003194 TI - Homogeneity of doping with paramagnetic ions by NMR. AB - In NMR, paramagnetic dopants change the relaxation behavior and the chemical shift of the nuclei in their immediate environment. Based on the concept that the "immediate environment" in a diamagnetic host material can be described as a sphere with radius r0, we developed a function for the fraction of unperturbed nuclei (the fraction of nuclei outside the sphere) which gives a link between the effective radius and the doping concentration. In the case of a homogeneous doping scenario a characteristic dependence is observed in both theory and experiment. We validated the model on a sample series where paramagnetic Eu(II) ions are doped into crystalline SrH2. The fraction of unperturbed nuclei was determined from the (1)H NMR signal and follows the predicted curve for a homogeneous doping scenario where the radius r0 is 17 A. PMID- 27003195 TI - Does Delay in Taking the American Board of Physical Medicine and Rehabilitation Certification Examinations Affect Passing Rates? AB - OBJECTIVES: The objective of this study was to examine whether a delay in initially taking the Part I or Part II American Board of Physical Medicine and Rehabilitation certification examinations influences the score or passing rates of candidates and whether enrollment in a subspecialty fellowship influences performance on the Part II certification examination. DESIGN: This was a retrospective review of first-time candidates taking the American Board of Physical Medicine and Rehabilitation initial certification examinations from 2010 to 2014. RESULTS: Passing rates declined as candidates delayed the examination past the time of initial eligibility. Passing rates for Part I were as follows (mean [95% confidence interval]): no delay, 91% (89%-94%); 1-yr delay, 68% (56% 82%); and more that 2 yrs' delay, 59% (55%-68%). For Part II, passing rates were as follows: no delay, 90% (85%-94%); 1-yr delay, 83% (72%-94%); and more than 2 yrs' delay, 68% (50%-83%). Those completing an accredited fellowship performed better (92% pass rate) on the Part II examination than did those who did not (81% pass rate), but they also had higher final year evaluations from their residency program directors. CONCLUSIONS: It seems preferable to take both Part I and Part II examinations as soon as one is eligible. Enrollment in an accredited fellowship may be associated with a higher chance of passing the examination. PMID- 27003196 TI - How Do Candidates Perform When Repeating the American Board of Physical Medicine and Rehabilitation Certification Examinations? AB - OBJECTIVE: The objective of this study was to examine the likelihood of passing the Part I and Part II American Board of Physical Medicine and Rehabilitation (ABPMR) certification examinations after initially failing. DESIGN: This was a retrospective review of candidates who had taken the ABPMR initial certification examinations between 2010 and 2014. RESULTS: Passing rates declined markedly with repeated attempts for both part I and part II. Passing rates (mean [95% confidence interval]) for part I were first attempt, 90% (87%-92%); second attempt, 58% (52%-66%); third attempt, 41% (26%-54%); fourth or greater attempt, 17% (3%-31%). For part II, the passing rates were first attempt, 87% (82%-92%); second attempt, 65% (56%-75%); third attempt, 41% (17%-65%); fourth or greater attempt, 20% (0%-59%). Those who were closer to the passing score on their initial attempt had a greater chance of passing on successive attempts. CONCLUSIONS: Passing rates for the ABPMR certification examination decline markedly with greater numbers of attempts. Those who fail again after one repeat attempt should rethink their examination preparation strategy before attempting the examination again. PMID- 27003197 TI - Ultrasound Imaging of Persistent Median Artery and Veins in an Asymptomatic Patient With a Bifid Median Nerve. PMID- 27003198 TI - Injury of the Ascending Reticular Activating System by Subfalcine Herniation After Subdural Hematoma: A Case Report. PMID- 27003199 TI - Ideomotor Apraxia Due to Injury of the Superior Longitudinal Fasciculus. AB - We report on a patient who showed ideomotor apraxia due to injury of the superior longitudinal fasciculus following brain tumor and tumor bleeding, which was demonstrated by diffusion tensor tractography (DTT). A 60-yr-old, right-handed male patient underwent removal of brain meningioma and drainage of intraventricular hemorrhage and intracerebral hemorrhage in the left fronto parietal lobe. At the time of DTT scanning (5 wk after onset), he was able to move the right upper extremity against gravity. The patient exhibited an intact ideational plan for motor performance. In addition, he was able to use actual objects (scissors, eraser) using his right wrist and hand. However, he had difficulty in using his right upper extremity for pantomime of object use, imitating gestures (meaningless or meaningful), and movement of his right upper extremity proximal. Score on the ideomotor apraxia test for the right side was 4 (cut-off score < 32). DTTs for the left superior longitudinal fasciculus to the left premotor cortex and left inferior parietal lobule showed partial injury, compared with the right superior longitudinal fasciculus. These injuries appeared to be the reason for ideomotor apraxia in this patient. PMID- 27003200 TI - "Numb Chin Syndrome": Two Additional Cases of Mental Nerve Mononeuropathy Resulting from Metastasis and Infection: -A Redux! PMID- 27003202 TI - Blind Injections: Ethical but not Eligible. PMID- 27003201 TI - Determining the Minimal Clinically Important Difference for 6-Minute Walk Distance in Fibromyalgia. AB - OBJECTIVE: The aim of this study was to estimate the minimal clinically important difference (MCID) for 6-min walk distance (6MWD) in patients with fibromyalgia. DESIGN: Data from a recently completed trial that included 187 patients who completed the 6-min walk test, Fibromyalgia Impact Questionnaire (FIQ), and Short Form 36 (SF36) at 12 and 36 wks were used to examine longitudinal changes in 6MWD. An anchor-based approach that used linear regression analyses was used to determine the MCID for 6MWD, using the total FIQ score (FIQ-Total) and SF36 physical function domain as clinical anchors. RESULTS: The mean (SD) change in 6MWD from baseline to week 36 was 34.4 (65.2) m (P < 0.001). The anchor-based MCIDs for the 6MWD were 156 and 167 m for the FIQ and SF36-physical function domain, respectively. These MCIDs correspond with clinically meaningful improvements in FIQ (14% reduction) and SF36-physical function domain (10-point increase). CONCLUSION: The MCID for 6MWD in patients with fibromyalgia was 156 to 167 m. These findings provide the first evidence of the change in 6MWD that is perceived by patients to be clinically meaningful. Further research using other MCID calculation methods is needed to refine estimates of the MCID for 6MWD in patients with fibromyalgia. PMID- 27003203 TI - Ultrasound Guidance for Technically Challenging Intrathecal Baclofen Pump Refill: Three Cases and Procedure Description. AB - Intrathecal baclofen (ITB) therapy is a common treatment used to reduce spasticity due to neurologic disorders and injuries. A variety of factors can increase the difficulty of ITB pump refill. Excess subcutaneous fat overlying the pump, spasticity, suboptimal positioning, pump rotation or inversion, and scar formation over the reservoir fill port can create challenges during pump refill. As a result, multiple unsuccessful attempts at accessing the reservoir fill port can be painful and increase the risk of infection, particularly when repeat skin puncture is required. Blind attempts to refill a pump in challenging cases may also result in subcutaneous injection or pocket fill, resulting in a potentially fatal baclofen withdrawal syndrome. We describe 3 successful ITB pump refills in technically challenging cases when using ultrasound guidance. This represents an innovative approach to using ultrasound guidance to facilitate ITB refill in adults with intractable spasticity. We present these new clinical data with a literature review of potential complications related to inaccurate pump refill procedures and discuss the utility of ultrasound guidance for preventing such adverse events. PMID- 27003204 TI - Hemiplegic Shoulder Pain Reduces Quality of Life After Acute Stroke: A Prospective Population-Based Study. AB - OBJECTIVE: Hemiplegic shoulder pain is a common complication of stroke. The primary aim of this study was to determine the association of hemiplegic shoulder pain with health-related quality of life at 12 months after first stroke in a population-based registry. The secondary aim was to identify other factors associated with health-related quality-of-life outcomes. DESIGN: A prospective population-based study in a geographically defined region of Adelaide, South Australia was conducted. Multiple ascertainment methods identified all cases of stroke within a 12-month period. Objective and subjective measures were undertaken at baseline and at 4 and 12 months' follow-up. Multiple regression analyses identified independent variables (including exposure to shoulder pain and depression, 12-month dependence, access to formal rehabilitation) associated with health-related quality of life, defined by the summary index score derived from EuroQol-5D-3L at 12 months post-stroke. RESULTS: Hemiplegic shoulder pain, depression, increased dependency, stroke severity, and absence of initial rehabilitation were each associated with reduction in quality of life. Age, sex, stroke type, Oxfordshire classification, and discharge destination were not related to quality of life. CONCLUSION: Hemiplegic shoulder pain reduces health related quality of life at 12 months. More effort should be directed towards screening and management of this frequent complication of stroke. PMID- 27003205 TI - Self-Selected and Maximal Walking Speeds Provide Greater Insight Into Fall Status Than Walking Speed Reserve Among Community-Dwelling Older Adults. AB - OBJECTIVE: To determine the degree to which self-selected walking speed (SSWS), maximal walking speed (MWS), and walking speed reserve (WSR) are associated with fall status among community-dwelling older adults. DESIGN: WS and 1-year falls history data were collected on 217 community-dwelling older adults (median age = 82, range 65-93 years) at a local outpatient PT clinic and local retirement communities and senior centers. WSR was calculated as a difference (WSRdiff = MWS - SSWS) and ratio (WSRratio = MWS/SSWS). RESULTS: SSWS (P < 0.001), MWS (P < 0.001), and WSRdiff (P < 0.01) were associated with fall status. The cutpoints identified were 0.76 m/s for SSWS (65.4% sensitivity, 70.9% specificity), 1.13 m/s for MWS (76.6% sensitivity, 60.0% specificity), and 0.24 m/s for WSRdiff (56.1% sensitivity, 70.9% specificity). SSWS and MWS better discriminated between fallers and non-fallers (SSWS: AUC = 0.69, MWS: AUC = 0.71) than WSRdiff (AUC = 0.64). CONCLUSIONS: SSWS and MWS seem to be equally informative measures for assessing fall status in community-dwelling older adults. Older adults with SSWSs less than 0.76 m/s and those with MWSs less than 1.13 m/s may benefit from further fall risk assessment. Combining SSWS and MWS to calculate an individual's WSR does not provide additional insight into fall status in this population. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Describe the different methods for calculating walking speed reserve and discuss the potential of the metric as an outcome measure; (2) Explain the degree to which self-selected walking speed, maximal walking speed, and walking speed reserve are associated with fall status among community-dwelling older adults; and (3) Discuss potential limitations to using walking speed reserve to identify fall status in populations without mobility restrictions. LEVEL: Advanced ACCREDITATION: : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity. PMID- 27003206 TI - Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head. AB - This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients. PMID- 27003207 TI - Exercise Prevents Amyloid-beta-Induced Hippocampal Network Disruption by Inhibiting GSK3beta Activation. AB - Exercise is becoming a promising therapeutic approach to prevent alterations both in Alzheimer's disease (AD) patients and in transgenic models of AD. This neuroprotection has been associated with changes in hippocampal structure and function, as well as with the reduction of amyloid-beta (Abeta) production and accumulation. However, whether exercise produces lasting changes in hippocampal population activity and renders it resistant to Abeta-induced network dysfunction is still unknown. Thus, we tested whether voluntary exercise changes hippocampal population activity and prevents its alteration in the presence of Abeta, which has been associated to glycogen synthase kinase-3beta (GSK3beta) activation. We found that the hippocampal population activity recorded in slices obtained from mice that exercised voluntarily (with free access to a running wheel for 21 days) exhibits higher power and faster frequency composition than slices obtained from sedentary animals. Moreover, the hippocampal network of mice that exercised becomes insensitive to Abeta-induced inhibition of spontaneous population activity. This protective effect correlates with the inability of Abeta to activate GSK3beta, is mimicked by GSK3beta inhibition with SB126763 (in slices obtained from sedentary mice), and is abolished by the inhibition of PI3K with LY294002 (in slices obtained from mice that exercised). We conclude that voluntary exercise produces a lasting protective state in the hippocampus, maintained in hippocampal slices by a PI3K-dependent mechanism that precludes its functional disruption in the presence of Abeta by avoiding GSK3beta activation. PMID- 27003208 TI - Expression of Tau Produces Aberrant Plasma Membrane Blebbing in Glial Cells Through RhoA-ROCK-Dependent F-Actin Remodeling. AB - Abnormal aggregation of Tau in glial cells has been reported in Alzheimer's disease (AD) and other tauopathies; however, the pathological significance of these aggregates remains unsolved to date. In this study, we evaluated whether full-length Tau (Tau441) and its aspartic acid421-truncated Tau variant (Tau421) produce alterations in the normal organization of the cytoskeleton and plasma membrane (PM) when transiently expressed in cultured C6-glial cells. Forty-eight hours post-transfection, abnormal microtubule bundling was observed in the majority of the cells, which expressed either Tau441 or Tau421. Moreover, both variants of Tau produced extensive PM blebbing associated with cortical redistribution of filamentous actin (F-Actin). These effects were reverted when Tau-expressing cells were incubated with drugs that depolymerize F-Actin. In addition, when glial cells showing Tau-induced PM blebbing were incubated with inhibitors of the Rho-associated protein kinase (ROCK) signaling pathway, both formation of abnormal PM blebs and F-Actin remodeling were avoided. All of these effects were initiated upstream by abnormal Tau-induced microtubule bundling, which may release the microtubule-bound guanine nucleotide exchange factor-H1 (GEF-H1) into the cytoplasm in order to activate its major effector RhoA-GTPase. These results may represent a new mechanism of Tau toxicity in which Tau-induced microtubule bundling produces activation of the Rho-GTPase-ROCK pathway that in turn mediates the remodeling of cortical Actin and PM blebbing. In AD and other tauopathies, these Tau-induced abnormalities may occur and contribute to the impairment of glial activity. PMID- 27003209 TI - Association of Plasma Abeta40 Peptides, But Not Abeta42, with Coronary Artery Disease and Diabetes Mellitus. AB - BACKGROUND/OBJECTIVE: Plasma levels of amyloid-beta (Abeta) 1-40 peptide have been proposed to be associated with cardiovascular mortality in patients with coronary artery disease (CAD). Therefore, we aimed to investigate the association of plasma Abeta levels with CAD, cardiovascular risk factors (CVRF), and APOE genotype in non-demented elderly individuals. METHODS: Plasma Abeta1 - 40 and Abeta1 - 42 levels of 526 individuals (mean age of 63.0+/-7.3 years) were quantified with the INNO-BIA plasma Abeta forms assay based on multiplextrademark technique. APOE genotype was determined with an established protocol. Presence of CAD and CVRFs were ascertained using a questionnaire and/or medical records. RESULTS: Plasma Abeta1 - 40 levels were significantly higher in individuals with CAD (p = 0.043) and, independently, in individuals with diabetes mellitus (DM) type 2 (p = 0.001) while accounting for age- and gender-effects. Plasma Abeta1 - 42 levels were higher in APOEE4 carriers (p = 0.004), but were neither relevantly associated with CAD nor with any CVRF. Plasma Abeta1 - 40 showed no association with APOE genotype. DISCUSSION: Our findings argue for an association of circulating plasma Abeta1 - 40 peptides with incident CAD and DM. Further investigations are needed to entangle the role of Abeta1 - 40 role in the pathophysiology of cardiovascular disease independent of its known role in Alzheimer's disease. PMID- 27003210 TI - Bridging Integrator 1 (BIN1) Genotypes Mediate Alzheimer's Disease Risk by Altering Neuronal Degeneration. AB - BACKGROUND: Bridging integrator 1 (BIN1) has been identified as one of the most associated loci for Alzheimer's disease (AD), and recently was reported to modulate tau pathology to mediate AD in vitro. However, the effects of BIN1 on the AD related biomarkers in AD continuum were not specifically assessed. OBJECTIVE: We explored the effects of BIN1 loci on AD specific biomarkers (CSF proteins, brain structures, glucose and amyloid-beta (Abeta) metabolisms) to investigate the role BIN1 in AD pathogenesis. METHODS: We calculated the associations of BIN1 loci with these markers at baseline and follow-up in multiple linear models in 812 ADNI subjects. RESULTS: BIN1 loci were significantly associated with the levels of T-tau (rs744373: pc = 0.047, rs13031703: pc = 0.042) and P-tau (rs744373: pc = 0.044, rs13031703: pc = 0.019), but not with Abeta in CSF test. BIN1 genotypes were strongly related to atrophy of hippocampus (rs7561528: pc = 0.011), CA1 (rs1469980: pc = 0.029) and parahippocampus (rs72838284, pc = 0.017) on MRI, and to glucose metabolism on FDG PET, but not to Abeta deposition on AV45-PET imaging. Furthermore, haplotype and subgroup analysis confirmed these significant findings. In addition, the loci associated with these markers were also identified to influence the risk for AD in the meta-analysis of 74 046 European individuals. CONCLUSION: This study supported that BIN1 contributes to the risk of AD by altering neural degeneration (abnormal tau, brain atrophy and glucose metabolism) but not Abeta pathology. PMID- 27003211 TI - Age-Related Effects of the Apolipoprotein E Gene on Brain Function. AB - The apolipoprotein E (ApoE) E4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE E4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4+/-4.6 years, 25 E4 carriers) and old (n = 40; age 66.1+/ 7.0 years, 20 E4 carriers) participants. A cross-sectional factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in E4 carriers. The increased BOLD response in old E4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the E4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young E4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age. PMID- 27003212 TI - ABCA7 Genotypes Confer Alzheimer's Disease Risk by Modulating Amyloid-beta Pathology. AB - ABCA7 gene has been identified as a strong genetic locus for Alzheimer's disease (AD) susceptibility in genome wide association studies (GWAS). However, the possible roles of ABCA7 variants in AD pathology were not specifically assessed. Using tagger methods, we extracted 15 targeted ABCA7 loci to investigate their associations with cerebrospinal fluid (CSF) and neuroimaging markers in Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Finally, although we did not detect any significant associations of previously published GWAS SNPs (rs3764650 and rs78117248) with all the CSF (Abeta1 - 42, T-tau, and P-tau) and neuroimaging markers, three other variants (rs3752242, rs3752240, and rs4147912) at ABCA7 loci were detected to show significant associations with amyloid deposition on AV-45 PET in brain. Moreover, haplotype and subgroup analysis confirmed these significant findings. Furthermore, there were no remarkable correlations between ABCA7 variants and neuronal degeneration biomarkers (elevated CSF tau, brain structure atrophy, and hypometabolism on imaging) in this study. Thus, our study suggested that ABCA7 genotypes contribute to the AD risk through involvement in amyloid-beta deposition on in vivo imaging, but not in tau pathology, brain atrophy, or decreased glucose metabolism. PMID- 27003213 TI - Dogs with Cognitive Dysfunction as a Spontaneous Model for Early Alzheimer's Disease: A Translational Study of Neuropathological and Inflammatory Markers. AB - Aged companion dogs with canine cognitive dysfunction (CCD) spontaneously develop varying degrees of progressive cognitive decline and particular neuropathological features correspondent to the changes associated with Alzheimer's disease (AD) in humans. The aim of the present study was to characterize certain aspects of neuropathology and inflammatory markers related to aging and CCD in dogs in comparison with human AD. Fifteen brains from aged dogs with normal cognitive function, mild cognitive impairment, or CCD were investigated and compared with two control brains from young dogs and brain sections from human AD subjects. The neuropathological investigations included evaluation of amyloid-beta (Abeta) plaque deposition (N-terminally truncated and pyroglutamyl-modified Abeta included), tau pathology, and inflammatory markers in prefrontal cortex. Cortical Abeta deposition was found to be only of the diffuse subtype as no dense-core or neuritic plaques were found. The Abeta deposition followed a progressive pattern in four maturation stages. Accumulation of the Abeta peptide was also observed in the vessel walls. Both immunohistochemically and biochemically measured levels of Abeta pathology in prefrontal cortex showed a consistent positive correlation to age but not to cognitive deficit severity. No evidence of neurofibrillary tau pathology was found. The level of pro-inflammatory cytokines was generally low and showed no significant association to cognitive status. The findings of the present study support the senescent dog with spontaneous cognitive dysfunction as a valuable non-transgenic model for further investigations of the molecular events involved in the neurodegenerative processes associated with aging and early stage AD, especially the Abeta-related pathology. PMID- 27003214 TI - M2 Macrophage Transplantation Ameliorates Cognitive Dysfunction in Amyloid-beta Treated Rats Through Regulation of Microglial Polarization. AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly population. Neuroinflammation induced by amyloid-beta (Abeta) aggregation is considered to be the critical factor underlying AD pathological mechanisms. Alternatively activated (M2) macrophages/microglia have been reported to have neuroprotective effects in neurodegenerative disease. In this study, we characterized the neuroprotective effects of M2 macrophage transplantation in AD model rats and investigated the underlying mechanisms. Intracerebroventricular injection of Abeta1 - 42 to rats was used to model AD and resulted in cognitive impairment, neuronal damage, and inflammatory changes in the brain microenvironment. We observed an increased interferon regulatory factor (IRF) 5/IRF4 ratio, resulting in greater production of classically activated (M1) versus M2 microglia. M2 macrophage transplantation attenuated inflammation in the brain, reversed Abeta1 - 42-induced changes in the IRF4-IRF5 ratio, drove endogenous microglial polarization toward the M2 phenotype, and ameliorated cognitive impairment. Nerve growth factor (NGF) treatment reduced the IRF5/IRF4 ratio and induced primary microglial polarization to the M2 phenotype in vitro; these effects were prevented by tyrosine Kinase Receptor A (TrkA) inhibition. M2 macrophage transplantation restored the balance of IRF4-IRF5 by affecting the expression of NGF and inflammatory cytokines in the brains of AD model rats. This drove microglial polarization to the M2 phenotype, promoted termination of neuroinflammation, and resulted in improved cognitive abilities. PMID- 27003215 TI - The Folate-Vitamin B12 Interaction, Low Hemoglobin, and the Mortality Risk from Alzheimer's Disease. AB - Abnormal hemoglobin levels are a risk factor for Alzheimer's disease (AD). Although the mechanism underlying these associations is elusive, inadequate micronutrients, particularly folate and vitamin B12, may increase the risk for anemia, cognitive impairment, and AD. In this study, we investigated whether the nutritional status of folate and vitamin B12 is involved in the association between low hemoglobin levels and the risk of AD mortality. Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and the NHANES (1999-2006) Linked Mortality File. A total of 4,688 participants aged >=60 years with available baseline data were included in this study. We categorized three groups based on the quartiles of folate and vitamin B12 as follows: Group I (low folate and vitamin B12); Group II (high folate and low vitamin B12 or low folate and high vitamin B12); and Group III (high folate and vitamin B12). Of 4,688 participants, 49 subjects died due to AD. After adjusting for age, sex, ethnicity, education, smoking history, body mass index, the presence of diabetes or hypertension, and dietary intake of iron, significant increases in the AD mortality were observed in Quartile1 for hemoglobin (HR: 8.4, 95% CI: 1.4-50.8), and the overall risk of AD mortality was significantly reduced with increases in the quartile of hemoglobin (p for trend = 0.0200), in subjects with low levels of both folate and vitamin B12 at baseline. This association did not exist in subjects with at least one high level of folate and vitamin B12. Our finding shows the relationship between folate and vitamin B12 levels with respect to the association between hemoglobin levels and AD mortality. PMID- 27003216 TI - Phenomenological Reliving and Visual Imagery During Autobiographical Recall in Alzheimer's Disease. AB - Multiple studies have shown compromise of autobiographical memory and phenomenological reliving in Alzheimer's disease (AD). We investigated various phenomenological features of autobiographical memory to determine their relative vulnerability in AD. To this aim, participants with early AD and cognitively normal older adult controls were asked to retrieve an autobiographical event and rate on a five-point scale metacognitive judgments (i.e., reliving, back in time, remembering, and realness), component processes (i.e., visual imagery, auditory imagery, language, and emotion), narrative properties (i.e., rehearsal and importance), and spatiotemporal specificity (i.e., spatial details and temporal details). AD participants showed lower general autobiographical recall than controls, and poorer reliving, travel in time, remembering, realness, visual imagery, auditory imagery, language, rehearsal, and spatial detail-a decrease that was especially pronounced for visual imagery. Yet, AD participants showed high rating for emotion and importance. Early AD seems to compromise many phenomenological features, especially visual imagery, but also seems to preserve some other features. PMID- 27003217 TI - A Population Perspective on Ethical Compliance with Drug Trial Standards of Practice. PMID- 27003218 TI - Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe. AB - Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN, TMEM106B, ABCC9, and KCNMB2 (minor allele frequency for each is >30%). A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (~50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults. PMID- 27003219 TI - Subthalamic Stimulation Reduces Vowel Space at the Initiation of Sustained Production: Implications for Articulatory Motor Control in Parkinson's Disease. AB - BACKGROUND: Stimulation of the subthalamic nuclei (STN) is an effective treatment for Parkinson's disease, but complaints of speech difficulties after surgery have been difficult to quantify. Speech measures do not convincingly account for such reports. OBJECTIVE: This study examined STN stimulation effects on vowel production, in order to probe whether DBS affects articulatory posturing. The objective was to compare positioning during the initiation phase with the steady prolongation phase by measuring vowel spaces for three "corner" vowels at these two time frames. METHODS: Vowel space was measured over the initial 0.25 sec of sustained productions of high front (/i/), high back (/u/) and low vowels (/a/), and again during a 2 sec segment at the midpoint. Eight right-handed male subjects with bilateral STN stimulation and seven age-matched male controls were studied based on their participation in a larger study that included functional imaging. Mean values: age = 57+/-4.6 yrs; PD duration = 12.3+/-2.7 yrs; duration of DBS = 25.6+/-21.2 mos, and UPDRS III speech score = 1.6+/-0.7. STN subjects were studied off medication at their therapeutic DBS settings and again with their stimulators off, counter-balanced order. RESULTS: Vowel space was larger in the initiation phase compared to the midpoint for both the control and the STN subjects off stimulation. With stimulation on, however, the initial vowel space was significantly reduced to the area measured at the mid-point. For the three vowels, the acoustics were differentially affected, in accordance with expected effects of front versus back position in the vocal tract. CONCLUSIONS: STN stimulation appears to constrain initial articulatory gestures for vowel production, raising the possibility that articulatory positions normally used in speech are similarly constrained. PMID- 27003220 TI - Temporal variation in the prevalence and species richness of Campylobacter spp. in a prairie watershed impacted by urban and agricultural mixed inputs. AB - Campylobacter spp. are a substantial cause of gastroenteritis worldwide. Human infection can result from ingestion of contaminated food or water from a variety of sources, including the consumption of fresh produce that is contaminated with the pathogen via the use of contaminated irrigation water. Using molecular methods, we investigated the occurrence of Campylobacter in the Qu'Appelle River watershed, an important source of irrigation water for vegetable producers in southern Saskatchewan, Canada. Water samples were collected from 7 sampling sites from April to September 2009 (145 samples), and from 5 sampling sites from May to October 2013 (116 samples). Campylobacter was detected in 57% and 16% of the samples collected in 2009 and 2013, respectively. Campylobacter detection was highest in May and June for both sampling years. In 2009, the predominant species were Campylobacter lari and Campylobacter jejuni, with prevalences of 84% and 41%, respectively. Other Campylobacter spp. were detected less frequently. Only C. lari was detected in 2013. The results in 2009 demonstrate the species richness of Campylobacter in water sources within the watershed. The occurrence of Campylobacter in the study area also underscores the importance of monitoring irrigation water used to irrigate fresh produce from a public health prospective. PMID- 27003221 TI - Treatment of Non-infectious Uveitic Macular Edema with the Intravitreal Dexamethasone Implant. AB - PURPOSE: To describe the clinical outcome of phakic eyes with macular edema (ME) due to non-infectious uveitis treated with a dexamethasone intravitreal implant. METHODS: A retrospective analysis of 41 eyes treated with a total of 58 dexamethasone intravitreal implants was conducted. Best corrected visual acuity (BCVA), central retinal thickness (CRT) and complications data were collected. RESULTS: One month after the first implant, even as CRT improved significantly in most eyes (p<0.001), 31.7% showed no improvement in BCVA. At 6 months post implantation, CRT and BCVA had deteriorated in up to 70% of patients. Thirteen eyes were re-implanted, with a similar effect to that of the first implant. Ocular hypertension developed in 36.2% of eyes, and three eyes had cataract surgery, all in eyes with repeated implants. CONCLUSIONS: The dexamethasone intravitreal implant can be safely used to treat ME due to non-infectious uveitis, but with a limited and short effect on BCVA. PMID- 27003222 TI - Long-term outcome of 154 patients receiving balloon-occluded retrograde transvenous obliteration for gastric fundal varices. AB - BACKGROUND AND AIM: This study aims to clarify the long-term outcome of therapeutic strategies including balloon-occluded retrograde transvenous obliteration (B-RTO) for patients with gastric fundal varices. METHODS: The subjects were 154 patients with gastric fundal varices fulfilling the criteria for receiving B-RTO. In patients showing variceal bleeding, endoscopic therapies and/or balloon tamponade was performed to achieve hemostasis. B-RTO was accomplished with injection of 5% ethanolamine oleate through a standard balloon catheter except for patients with atypical varices, in whom a microballoon catheter was used to occlude drainage vessels other than a gastrorenal shunt. In patients complicated with esophageal varices at baseline, endoscopic therapies were performed following B-RTO. RESULTS: Balloon-occluded retrograde transvenous obliteration was performed successfully in 147 patients (95%), including 15 patients using a microballoon catheter. Complete variceal obliteration was achieved in all patients. Additional endoscopic therapies for esophageal varices were performed in 31 patients. Gastric varices did not recur in any of these patients. The cumulative survival rates at 1, 3, and 5 years after B-RTO were 91%, 76%, and 72%, respectively. Child-Pugh scores and hepatocellular carcinoma complication were identified as prognostic factors associated with survival rates. The cumulative exacerbation rates of esophageal varices at 1, 3, and 5 years were 13%, 20%, and 27%, respectively, and rupture developed in six patients, which were successfully treated with endoscopic therapies. CONCLUSIONS: Therapeutic strategies including B-RTO with a microballoon catheter were useful to achieve a favorable outcome in patients with gastric fundal varices especially in those manifesting Child-Pugh class-A liver damage and/or those without hepatocellular carcinoma complication. PMID- 27003223 TI - Model-based estimation of microscopic anisotropy using diffusion MRI: a simulation study. AB - Non-invasive estimation of cell size and shape is a key challenge in diffusion MRI. This article presents a model-based approach that provides independent estimates of pore size and eccentricity from diffusion MRI data. The technique uses a geometric model of finite cylinders with gamma-distributed radii to represent pores of various sizes and elongations. We consider both macroscopically isotropic substrates and substrates of semi-coherently oriented anisotropic pores and we use Monte Carlo simulations to generate synthetic data. We compare the sensitivity of single and double diffusion encoding (SDE and DDE) sequences to the size distribution and eccentricity, and further analyse different protocols of DDE sequences with parallel and/or perpendicular pairs of gradients. We show that explicitly accounting for size distribution is necessary for accurate microstructural parameter estimates, and a model that assumes a single size yields biased eccentricity values. We also find that SDE sequences support estimates, although DDE sequences with mixed parallel and perpendicular gradients enhance accuracy. In the case of macroscopically anisotropic substrates, this model-based approach can be extended to a rotationally invariant framework to provide features of pore shape (specifically eccentricity) in the presence of size distribution and orientation dispersion. PMID- 27003224 TI - The ecological drivers of nuptial color evolution in darters (Percidae: Etheostomatinae). AB - Closely related animal lineages often vary in male coloration, and ecological selection is hypothesized to shape this variation. The role of ecological selection in inhibiting male color has been documented extensively at the population level, but relatively few studies have investigated the evolution of male coloration across a clade of closely related species. Darters are a diverse group of fishes that vary in the presence of elaborate male nuptial coloration, with some species exhibiting vivid color patterns and others mostly or entirely achromatic. We used phylogenetic logistic regression to test for correlations between the presence/absence of color traits across darter species and the ecological conditions in which these species occur. Environmental variables were correlated with the presence of nuptial color in darters with colorful species tending to inhabit environments that would support fewer predators and potentially transmit a broader spectrum of natural light compared to species lacking male coloration. We also tested the color preferences of a common darter predator, largemouth bass, and found that it exhibits a strong preference for red, providing further evidence of predation as a source of selection on color evolution in darters. Ecological selection therefore appears to be an important factor in dictating the presence or absence of male coloration in this group of fishes. PMID- 27003225 TI - 3D evaluation of mandibular skeletal changes in juvenile arthritis patients treated with a distraction splint: A retrospective follow-up. AB - OBJECTIVE: To evaluate three-dimensional (3D) condylar and mandibular growth in patients with juvenile idiopathic arthritis (JIA) with unilateral temporomandibular joint involvement treated with a distraction splint. MATERIALS AND METHODS: Cone-beam computed tomography (CBCT) scans were taken for 16 patients with JIA with unilateral TMJ involvement before treatment (T0) and 2 years after treatment (T1). All patients received orthopedic treatment with a distraction splint. Eleven patients without JIA who were undergoing orthodontic treatment without a functional appliance or Class II mechanics and who had taken CBCT scans before and after treatment, served as controls. Reconstructed 3D models of the mandibles at T0 and T1 were superimposed on stable structures. Intra- and intergroup growth differences in condylar and mandibular ramus modifications and growth vector direction of the mandibular ramus were evaluated. RESULTS: In all patients with JIA there were asymmetric condylar volume, distal and vertical condylar displacement, and ramus length differences that were smaller on the affected side. Condylar displacement was more distal and less vertical in the JIA group than in the control group. A larger distal growth of the condylar head and a more medial rotation of the ramus on the affected side were found in the JIA group. CONCLUSION: The orthopedic functional treatment for patients with JIA allows for condylar adaptation and modeling, thereby hindering, although with a widely variable response, a further worsening of the asymmetry. Unilateral affection has a possible influence on the growth of the nonaffected side. PMID- 27003226 TI - Indirect arterial blood pressure measurement in healthy anesthetized cats using a device that combines oscillometry with photoplethysmography. AB - We investigated the basic characteristics of indirect arterial blood pressure (ABP) measurement using a device that combines oscillometry and photoplethysmography in cats. Dobutamine was infused intravenously in four anesthetized cats. Direct ABP was measured by a catheter. Indirect ABP was measured from the left forelimb. Dobutamine significantly elevated both systolic arterial pressure (SAP) and mean arterial pressure (MAP) in a dose-dependent manner. The indirect SAP, MAP and diastolic arterial pressure (DAP) values were closely correlated with the direct ABP values (r=0.88, 0.89 and 0.83, respectively). The mean bias for SAP, MAP and DAP was 3.4, 0.2 and -2.4 mmHg, respectively. The indirect ABP measured by this device may be used to reliably monitor ABP changes in anesthetized cats. PMID- 27003229 TI - Conversion of Nitric Oxide into Nitrous Oxide as Triggered by the Polarization of Coordinated NO by Hydrogen Bonding. AB - Reduction of the {Co(NO)}(8) cobalt-nitrosyl N-confused porphyrin (NCP) [Co(CTPPMe)(NO)] (1) produced electron-rich {Co(NO)}(9) [Co(CTPPMe)(NO)][Co(Cp*)2 ] (2), which was necessary for NO-to-N2 O conversion. Complex 2 was NO-reduction silent in neat THF, but was partially activated to a hydrogen-bonded species 2???MeOH in THF/MeOH (1:1, v/v). This species coupling with 2 transformed NO into N2 O, which was fragmented from an [N2 O2 ]-bridging intermediate. An intense IR peak at 1622 cm(-1) was ascribed to nu(NO) in an [N2 O2 ]-containing intermediate. Time-course ESI(-) mass spectra supported the presence of the dimeric [Co(NCP)]2 (N2 O2 ) intermediate. Five complete NO-to-N2 O conversion cycles were possible without significant decay in the amount of N2 O produced. PMID- 27003228 TI - Selective binding and lateral clustering of alpha5beta1 and alphavbeta3 integrins: Unraveling the spatial requirements for cell spreading and focal adhesion assembly. AB - Coordination of the specific functions of alpha5beta1 and alphavbeta3 integrins is crucial for the precise regulation of cell adhesion, spreading and migration, yet the contribution of differential integrin-specific crosstalk to these processes remains unclear. To determine the specific functions of alphavbeta3 and alpha5beta1 integrins, we used nanoarrays of gold particles presenting immobilized, integrin-selective peptidomimetic ligands. Integrin binding to the peptidomimetics is highly selective, and cells can spread on both ligands. However, spreading is faster and the projected cell area is greater on alpha5beta1 ligand; both depend on ligand spacing. Quantitative analysis of adhesion plaques shows that focal adhesion size is increased in cells adhering to alphavbeta3 ligand at 30 and 60 nm spacings. Analysis of alphavbeta3 and alpha5beta1 integrin clusters indicates that fibrillar adhesions are more prominent in cells adhering to alpha5beta1 ligand, while clusters are mostly localized at the cell margins in cells adhering to alphavbeta3 ligand. alphavbeta3 integrin clusters are more pronounced on alphavbeta3 ligand, though they can also be detected in cells adhering to alpha5beta1 ligand. Furthermore, alpha5beta1 integrin clusters are present in cells adhering to alpha5beta1 ligand, and often colocalize with alphavbeta3 clusters. Taken together, these findings indicate that the activation of alphavbeta3 integrin by ligand binding is dispensable for initial adhesion and spreading, but essential to formation of stable focal adhesions. PMID- 27003227 TI - Sparse Reconstruction Techniques in Magnetic Resonance Imaging: Methods, Applications, and Challenges to Clinical Adoption. AB - The family of sparse reconstruction techniques, including the recently introduced compressed sensing framework, has been extensively explored to reduce scan times in magnetic resonance imaging (MRI). While there are many different methods that fall under the general umbrella of sparse reconstructions, they all rely on the idea that a priori information about the sparsity of MR images can be used to reconstruct full images from undersampled data. This review describes the basic ideas behind sparse reconstruction techniques, how they could be applied to improve MRI, and the open challenges to their general adoption in a clinical setting. The fundamental principles underlying different classes of sparse reconstructions techniques are examined, and the requirements that each make on the undersampled data outlined. Applications that could potentially benefit from the accelerations that sparse reconstructions could provide are described, and clinical studies using sparse reconstructions reviewed. Lastly, technical and clinical challenges to widespread implementation of sparse reconstruction techniques, including optimization, reconstruction times, artifact appearance, and comparison with current gold standards, are discussed. PMID- 27003230 TI - Autologous Cord Blood Cells Infusion as Salvage Therapy for Engraftment Failure After Haploidentical Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia. PMID- 27003231 TI - Measurements of Repeated Tightening and Loosening Torque of Seven Different Implant/Abutment Connection Designs and Their Modifications: An In Vitro Study. AB - PURPOSE: Repeated tightening and loosening of the abutment screw may alter its mechanical and physical properties affecting the optimal torque and ultimate reliability of an implant/abutment connection. The purpose of this study was to evaluate the effect of repeated tightening and loosening of implant/abutment screws on the loosening torque of implant/abutment connections of commercially available implant systems. MATERIALS AND METHODS: Seven different implant/abutment connections and their modifications were tested. The screws of each system were tightened according to the manufacturer's specifications. After 20 minutes the screws were loosened. This procedure was repeated ten times, and the differences between the 1st and 10th cycle were expressed as a percentage change RTq(%) and correlated with initial torque, the number of threads, the length of shank, and thread surface area employing Spearman's analysis. RESULTS: All systems showed significant differences in residual torque (RTq) value (p < 0.05) between the 1st and 10th cycle except groups 6 and 11 (p > 0.05). All connections but group 3 (p = 1.000) showed a significant change from the initial torque (ITq) to the RTq values. The first successive RTq values increased in two connection groups 1 and 2. The remaining connections showed reduced RTq values ranging from -1.2 % (group 5) to -23.5% (group 6). The RTq values declined gradually with every repeated tightening in groups 1, 2, 3, 8, 9, 11, 12. In group 2, after the tenth tightening the RTq was still above the ITq value. Only length of shank demonstrated a correlation with the RTq(%) change over the successive tightening loosening cycles (p < 0.05). CONCLUSION: Repeated tightening and loosening of implant/abutment screws caused varying torque level changes among the different systems. These observations can probably be attributed to connection design. CLINICAL IMPLICATIONS: Limiting the number of tightening/loosening cycles in clinical and laboratory procedures is advisable for most of the implant systems tested. PMID- 27003232 TI - Beneficial Effect on Surrogate Markers of Heart Failure with Bisoprolol Up Titration to Recommended Targets in Korean Patients with Heart Failure and Left Ventricular Systolic Dysfunction. AB - INTRODUCTION: The objective of this study was to establish the benefit of bisoprolol up-titration toward recommended dosage targets, versus lower-dose maintenance, in heart failure (HF) patients with systolic dysfunction. METHODS: Korean HF patients received bisoprolol 1.25 mg/day, incrementally up-titrated toward 10 mg/day in the absence of contraindications. After 26 weeks' treatment, patients were grouped as low-dose (<3.75 mg/day) or high-dose (>=3.75 mg/day). Primary endpoint was change in serum N-terminal probrain natriuretic peptide (NT proBNP). Other markers of HF were also evaluated. RESULTS: 159 of 180 enrolled patients were evaluable. After 16 weeks' follow-up, there were 52 and 107 patients in the low- and high-dose groups respectively. Mean bisoprolol dosage was 5.4 mg/day; 24% of patients achieved target (10 mg/day). Mean logNT-proBNP significantly decreased in both groups, with no significant difference in the magnitude of change between groups. Mean heart rate (HR) and blood pressure decreased significantly in both groups, but only HR showed a significantly greater change in high-dose versus low-dose patients. In both groups, mean left ventricular (LV) end-systolic and end-diastolic dimensions were significantly decreased and mean LV ejection fraction was significantly improved. Mean 6-min walk test distances improved in both groups (significant in low-dose patients only). Functional class improvement was observed in both low- and high-dose patients. No patients were rehospitalized due to aggravated HF. CONCLUSIONS: In HF patients with systolic dysfunction, any bisoprolol dose is beneficial, but an attempt to up-titrate toward guideline-recommended dosages offers additional benefit in terms of restoration of LV systolic function and remodeling. PMID- 27003233 TI - Influence of osteoclasts and osteoprotegerin on the mode of calcific degeneration of aortic valves. AB - INTRODUCTION: Calcific aortic valve disease is associated with inflammation and calcification, thus the osteoprotegerin (OPG), receptor activator of nuclear factor kappaB (RANK) and its ligand (RANKL) system involved in osteoclastogenesis and inflammation may play a significant role in valve degeneration. OBJECTIVES: The aim of this study was to assess whether circulating OPG, sRANKL, and other bone metabolism markers can predict the presence of osteoclasts in stenotic valves and to evaluate their impact on the mode of degeneration. PATIENTS AND METHODS: The study involved 60 patients with aortic stenosis who underwent valve replacement surgery and subsequently were divided into 2 groups: osteoclastic (n = 12) and nonosteoclastic (n = 48), according to the presence or absence of intravalvular osteoclasts. Before the surgery, we measured serum levels of OPG, sRANKL, osteocalcin, osteopontin, tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, and IL-6. Immunohistochemistry and morphometry were used to determine the extent of valve calcification, lipid accumulation, neovascularization, and the number and phenotype of macrophages. RESULTS: Compared with the nonosteoclastic group, patients with intravalvular osteoclasts had lower levels of OPG (P = 0.0006) and TNF-alpha (P = 0.02) and less frequently had diabetes (P = 0.04). Their valves showed higher incidence of ossification (P = 0.002), higher total (P = 0.008) and M2 macrophage counts (P = 0.0002), increased neovascularization (P = 0.003), and lower accumulation of lipids (P = 0.04). They also showed a negative correlation between valve calcification and age (r = -0.79, P = 0.002), which was not observed in patients without osteoclasts. In a multivariate analysis, low circulating OPG levels and the absence of diabetes were predictors of intravalvular osteoclastic differentiation. CONCLUSIONS: The presence of osteoclasts in stenotic valves associated with low circulating OPG levels and an enhanced proportion of M2 macrophages can represent a variant of calcific aortic valve disease with a specifically regulated calcification process. PMID- 27003234 TI - Correction to Alternative Conformations of Cytochrome c: Structure, Function, and Detection. PMID- 27003235 TI - Femtosecond Stimulated Raman Exposes the Role of Vibrational Coherence in Condensed-Phase Photoreactivity. AB - Femtosecond spectroscopy has revealed coherent wave packet motion time and time again, but the question as to whether these coherences are necessary for reactivity or merely a consequence of the experiment has remained open. For diatomic systems in the gas phase, such as sodium iodide, the dimensionality of the system requires coordinated atomic motion along the reaction coordinate. Coherent dynamics are also readily observed in condensed-phase multidimensional systems such as chromophores in proteins and solvated charge transfer dimers. Is precisely choreographed nuclear motion (i.e., coherence) required for reactivity in these systems? Can this coherence reveal anything about the reaction coordinate? In this Account, we describe our efforts to tackle these questions using femtosecond stimulated Raman spectroscopy (FSRS). Results of four exemplary systems are summarized to illustrate the role coherence can play in condensed phase reactivity, the exploitation of vibrational coherence to measure vibrational anharmonicities, and the development of two-dimensional FSRS (2D FSRS). We begin with rhodopsin, the protein responsible for vertebrate vision. The rhodopsin photoreaction is preternaturally fast: ground-state photoproduct is formed in less than 200 fs. However, the reactively important hydrogen out-of plane motions as well as various torsions and stretches remain vibrationally coherent long after the reaction is complete, indicating that vibrational coherence can and does survive reactive internal conversion. Both the ultrashort time scale of the reaction and the observed vibrational coherence indicate that the reaction in rhodopsin is a vibrationally coherent process. Next we examine the functional excited-state proton transfer (ESPT) reaction of green fluorescent protein. Oscillations in the phenoxy C-O and imidazolinone C?N stretches in the FSRS spectrum indicated strong anharmonic coupling to a low-frequency phenyl wagging mode that gates the ESPT reaction. In this case, the coherence revealed not only itself but also the mode coupling that is necessary for reactivity. Curious as to whether vibrational coherence is a common phenomenon, we examined two simpler photochemical systems. FSRS studies of the charge transfer dimer tetramethylbenzene:tetracyanoquinodimethane revealed many vibrational oscillations with high signal-to-noise ratio that allowed us to develop a 2D-FSRS technique to quantitatively measure anharmonic vibrational coupling for many modes within a reacting excited state. Armed with this technique, we turned our attention to a bond-breaking reaction, the cycloreversion of a cyclohexadiene derivative. By means of 2D-FSRS, the vibrational composition of the excited-state transition state and therefore the reaction coordinate was revealed. In aggregate, these FSRS measurements demonstrate that vibrational coherences persist for many picoseconds in condensed phases at room temperature and can survive reactive internal conversion. Moreover, these coherences can be leveraged to reveal quantitative anharmonic couplings between a molecule's normal modes in the excited state. These anharmonic couplings are the key to determining how normal modes combine to form a reaction coordinate. It is becoming clear that condensed-phase photochemical reactions that occur in 10 ps or less require coordinated, coherent nuclear motion for efficient reactive internal conversion. PMID- 27003236 TI - The effect of FLT3-ITD and NPM1 mutation on survival in intensively treated elderly patients with cytogenetically normal acute myeloid leukemia. PMID- 27003237 TI - Regio- and Enantioselective Synthesis of Azole Hemiaminal Esters by Lewis Base Catalyzed Dynamic Kinetic Resolution. AB - We report a modular three-component dynamic kinetic resolution (DKR) that affords enantiomerically enriched hemiaminal esters derived from azoles and aldehydes. The novel and scalable reaction can be used to synthesize valuable substituted azoles in a regioselective manner by capping (e.g., acylation) of the equilibrating azole-aldehyde adduct. With the use of a prolinol-derived DMAP catalyst as the chiral Lewis base, the products can be obtained in high chemical yield and with high enantiomeric excess. The DKR was performed on a multikilogram scale to produce a tetrazole prodrug fragment for a leading clinical candidate that posed formidable synthesis challenges. PMID- 27003238 TI - Nanoparticle-based measurements of pH and O2 dynamics in the rhizosphere of Zostera marina L.: effects of temperature elevation and light-dark transitions. AB - Seagrasses can modulate the geochemical conditions in their immediate rhizosphere through the release of chemical compounds from their below-ground tissue. This is a vital chemical defence mechanism, whereby the plants detoxify the surrounding sediment. Using novel nanoparticle-based optical O2 and pH sensors incorporated in reduced and transparent artificial sediment, we investigated the spatio temporal dynamics of pH and O2 within the entire rhizosphere of Zostera marina L. during experimental manipulations of light and temperature. We combined such measurements with O2 microsensor measurements of the photosynthetic productivity and respiration of seagrass leaves. We found pronounced pH and O2 microheterogeneity within the immediate rhizosphere of Z. marina, with higher below-ground tissue oxidation capability and rhizoplane pH levels during both light exposure of the leaf canopy and elevated temperature, where the temperature mediated stimuli of biogeochemical processes seemed to predominate. Low rhizosphere pH microenvironments appeared to correlate with plant-derived oxic microzones stimulating local sulphide oxidation and thus driving local proton generation, although the rhizoplane pH levels generally where much higher than the bulk sediment pH. Our data show that Z. marina can actively alter its rhizosphere pH microenvironment alleviating the local H2 S toxicity and enhancing nutrient availability in the adjacent sediment via geochemical speciation shift. PMID- 27003239 TI - The epidemiological and serological characteristics of measles in Dongguan, China, 2005-2014. AB - This study examined the epidemiological and serological characteristics of measles in Dongguan, China. From 2005 to 2014, a total of 8,224 measles cases were reported in Dongguan, 33.5% of which were aged <1 y and 30.6% >14 y. From 2005 to 2014, the proportion of the <1 y measles cases increased year by year from 24.3% to 47.9%. Of the cases aged >=8 months (n = 6,768 cases), only 11.6% had been immunized with at least one dose of measles vaccine. Of the 2,213 cases who had never been immunized with measles vaccine, immigrants accounted for 82.4%. 52.4% of the measles cases were diagnosed with pneumonia, and 12 cases died from respiratory failure. Seroprevalence rate in women and their newborns was 86.0% and 82.5%, respectively. Measurement of serum measles antibody levels for infants aged less than 8 months indicated that seroprevalence rate dramatically declined from 97.3% at birth to 9.3% and 13.2% at 6- and 7- month old. The existence of a sufficient pool of unvaccinated people (especially immigrants) and decreased level of passively transferred measles antibodies in infants from vaccinated mothers contributed to the sustained transmission observed in Dongguan. In addition to high routine vaccination coverage, new strategies and innovations for measles vaccination are needed to eliminate measles. PMID- 27003240 TI - The Day the President of the United States Said "That Data is Mine". PMID- 27003241 TI - Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation. AB - Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures. PMID- 27003242 TI - Effects of Tai Chi training on postural control and cognitive performance while dual tasking - a randomized clinical trial. AB - BACKGROUND: This single-blinded, randomized controlled study investigated the effects of practicing Tai Chi on the postural control and cognitive performance of older women while dual tasking. METHODS: Community-dwelling older women (n=31) were recruited from community centers. They were randomized to Tai Chi group (n=15, 12-form Yang style Tai Chi training) or a control group (n=16, general interest classes) for 16 weeks. Balance was tested in single leg stance after stepping down from a step, with and without a concurrent auditory response task (auditory Stroop test). Balance was measured by total sway path and sway area of subject's center of pressure (COP). The reaction time and the correctness of the auditory Stroop test were also measured. RESULTS: Tai Chi subjects made fewer errors in auditory Stroop test under dual-task condition after Tai Chi training (p=0.01). They also showed significant decreases in the COP path (p<0.05) and the COP area (p<0.05) in their postural control after training in both single- and dual-task conditions. The subjects in the control group did not show any significant improvement in dual-task condition after the intervention. CONCLUSIONS: Tai Chi training improves the cognitive and postural control performance of older women when dual tasking. PMID- 27003243 TI - Thieno[2,3-b]indole-Based Small Push-Pull Chromophores: Synthesis, Structure, and Electronic Properties. AB - Small push-pull molecules were synthesized in high yields by connecting a N methyl or N-phenyl substituted thieno[2,3-b]indole electron-donating block directly to a 2,2-dicyanovinyl or (1-(dicyanomethylene)-3-oxo-1-inden-2 ylidene)methyl electron-withdrawing group. The effects of the N-substitution on thieno[2,3-b]indole and the nature of the electron-accepting group on the electrochemical, optical, and charge-transport properties were investigated by cyclic voltammetry, UV-vis spectroscopy, and the space-charge-limited current method, respectively. These results, together with the 1% power conversion efficiency of a bilayer solar cell prepared with the smallest compound of the series, show the potential of thieno[2,3-b]indole for organic electronics. PMID- 27003244 TI - Diversity and oceanic distribution of the Parmales (Bolidophyceae), a picoplanktonic group closely related to diatoms. AB - Bolidomonas is a genus of picoplanktonic flagellated algae that is closely related to diatoms. Triparma laevis, a species belonging to the Parmales, which are small cells with a siliceous covering, has been shown to form a monophyletic group with Bolidomonas. We isolated several novel strains of Bolidophyceae that have permitted further exploration of the diversity of this group using nuclear, plastidial and mitochondrial genes. The resulting phylogenetic data led us to formally emend the taxonomy of this group to include the Parmales within the Bolidophyceae, to combine Bolidomonas within Triparma and to define a novel species, Triparma eleuthera sp. nov. The global distribution of Bolidophyceae was then assessed using environmental sequences available in public databases, as well as a large 18S rRNA V9 metabarcode data set from the Tara Oceans expedition. Bolidophyceans appear ubiquitous throughout the sampled oceans but always constitute a minor component of the phytoplankton community, corresponding to at most ~4% of the metabarcodes from photosynthetic groups (excluding dinoflagellates). They are ~10 times more abundant in the small size fraction (0.8-5 MUm) than in larger size fractions. T. eleuthera sp. nov. constitutes the most abundant and most widespread operational taxonomic unit (OTU) followed by T. pacifica, T. mediterranea and the T. laevis clade. The T. mediterranea OTU is characteristic of Mediterranean Sea surface waters and the T. laevis clade OTU is most prevalent in colder waters, in particular off Antarctica. PMID- 27003245 TI - Defining the microbial transcriptional response to colitis through integrated host and microbiome profiling. AB - The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess modifications to both bacterial community structure and transcriptional activity in a mouse model of colitis. By using transcriptomic analysis of colonic tissue and luminal RNA derived from the host, we have also characterised how host transcription relates to the microbial transcriptional response in inflammation. In colitis, increased abundance and transcription of diverse microbial gene families involved in responses to nutrient deprivation, antimicrobial peptide production and oxidative stress support an adaptation of multiple commensal genera to withstand a diverse set of environmental stressors in the inflammatory environment. These data are supported by a transcriptional signature of activated macrophages and granulocytes in the gut lumen during colitis, a signature that includes the transcription of the key antimicrobial genes S100a8 and S100a9 (calprotectin). Genes involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase were identified as changing to a greater extent at the level of transcription than would be predicted by DNA abundance changes, implicating a role for increased oxygen tension and/or host-derived reactive oxygen species in driving transcriptional changes in commensal microbes. PMID- 27003246 TI - Regulation of Sticholysin II-Induced Pore Formation by Lipid Bilayer Composition, Phase State, and Interfacial Properties. AB - Sticholysin II (StnII) is a pore-forming toxin that uses sphingomyelin (SM) as the recognition molecule in targeting membranes. After StnII monomers bind to SM, several toxin monomers act in concert to oligomerize into a functional pore. The regulation of StnII binding to SM, and the subsequent pore-formation process, is not fully understood. In this study, we examined how the biophysical properties of bilayers, originating from variations in the SM structure, from the presence of sterol species, or from the presence of increasingly polyunsaturated glycerophospholipids, affected StnII-induced pore formation. StnII-induced pore formation, as determined from calcein permeabilization, was fastest in the pure unsaturated SM bilayers. In 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/saturated SM bilayers (4:1 molar ratio), pore formation became slower as the chain length of the saturated SMs increased from 14 up to 24 carbons. In the POPC/palmitoyl-SM (16:0-SM) 4:1 bilayers, SM could not support pore formation by StnII if dimyristoyl-PC was included at 1:1 stoichiometry with 16:0-SM, suggesting that free clusters of SM were required for toxin binding and/or pore formation. Cholesterol and other sterols facilitated StnII-induced pore formation markedly, but the efficiency did not appear to correlate with the sterol structure. Benzyl alcohol was more efficient than sterols in enhancing the pore formation process, suggesting that the effect on pore formation originated from alcohol-induced alteration of the hydrogen-bonding network in the SM-containing bilayers. Finally, we observed that pore formation by StnII was enhanced in the PC/16:0-SM 4:1 bilayers, in which the PC was increasingly unsaturated. We conclude that the physical state of bilayer lipids greatly affected pore formation by StnII. Phase boundaries were not required for pore formation, although SM in a gel state attenuated pore formation. PMID- 27003247 TI - Treatment for chronic methicillin-sensitive Staphylococcus aureus pulmonary infection in people with cystic fibrosis. AB - BACKGROUND: Cystic fibrosis is an inherited life-threatening multisystem disorder with lung disease characterized by abnormally thick airway secretions and persistent bacterial infection. Chronic, progressive lung disease is the most important cause of morbidity and mortality in the condition and is therefore the main focus of clinical care and research. Staphylococcus aureus is a major cause of chest infection in people with cystic fibrosis. Early onset, as well as chronic, lung infection with this organism in young children and adults results in worsening lung function, poorer nutrition and increases the airway inflammatory response, thus leading to a poor overall clinical outcome. There are currently no evidence-based guidelines for chronic suppressive therapy for Staphylococcus aureus infection in cystic fibrosis such as those used for Pseudomonas aeruginosa infection. OBJECTIVES: To assess the evidence regarding the effectiveness of long-term antibiotic treatment regimens for chronic infection with methicillin-sensitive Staphylococcus aureus (MSSA) infection in people with cystic fibrosis and to determine whether this leads to improved clinical and microbiological outcomes. SEARCH METHODS: Trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, Embase, handsearching article reference lists and through contact with local and international experts in the field. We also searched ongoing trials databases.Date of the last search of the Group's Cystic Fibrosis Trials Register: 03 March 2016. SELECTION CRITERIA: Randomised or quasi randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials used as suppressive therapy for chronic infection with methicillin-sensitive Staphylococcus aureus compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: The authors independently assessed all search results for eligibility. No eligible trials were identified. MAIN RESULTS: The searches identified 55 trials, but none were eligible for inclusion in the current version of this review. AUTHORS' CONCLUSIONS: No randomised controlled trials were identified which met the inclusion criteria for this review. Although methicillin-sensitive Staphylococcus aureus is an important and common cause of lung infection in people with cystic fibrosis, there is no agreement on how best to treat long-term infection. The review highlights the need to organise well designed trials that can provide evidence to support the best management strategy for chronic methicillin-sensitive Staphylococcus aureus infection in people with cystic fibrosis. PMID- 27003248 TI - Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection. AB - The deregulation of cellular long non-coding RNA (lncRNA) expression during a human adenovirus infection was studied by deep sequencing. Expression of lncRNAs increased substantially following the progression of the infection. Among 645 significantly expressed lncRNAs, the expression of 398 was changed more than 2 fold. More than 80% of them were up-regulated and 80% of them were detected during the late phase. Based on the genomic locations of the deregulated lncRNAs in relation to known mRNAs and miRNAs, they were predicted to be involved in growth, structure, apoptosis and wound healing in the early phase, cell proliferation in the intermediate phase and protein synthesis, modification and transport in the late phase. The most significant functions of cellular RNA binding proteins, previously shown to interact with the deregulated lncRNAs identified here, are involved in RNA splicing, nuclear export and translation events. We hypothesize that adenoviruses exploit the lncRNA network to optimize their reproduction. PMID- 27003249 TI - Understanding the control of acyl flux through the lipid metabolic network of plant oil biosynthesis. AB - Plant oil biosynthesis involves a complex metabolic network with multiple subcellular compartments, parallel pathways, cycles, and pathways that have a dual function to produce essential membrane lipids and triacylglycerol. Modern molecular biology techniques provide tools to alter plant oil compositions through bioengineering, however with few exceptions the final composition of triacylglycerol cannot be predicted. One reason for limited success in oilseed bioengineering is the inadequate understanding of how to control the flux of fatty acids through various fatty acid modification, and triacylglycerol assembly pathways of the lipid metabolic network. This review focuses on the mechanisms of acyl flux through the lipid metabolic network, and highlights where uncertainty resides in our understanding of seed oil biosynthesis. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID- 27003250 TI - Assessing compartmentalized flux in lipid metabolism with isotopes. AB - Metabolism in plants takes place across multiple cell types and within distinct organelles. The distributions equate to spatial heterogeneity; though the limited means to experimentally assess metabolism frequently involve homogenizing tissues and mixing metabolites from different locations. Most current isotope investigations of metabolism therefore lack the ability to resolve spatially distinct events. Recognition of this limitation has resulted in inspired efforts to advance metabolic flux analysis and isotopic labeling techniques. Though a number of these efforts have been applied to studies in central metabolism; recent advances in instrumentation and techniques present an untapped opportunity to make similar progress in lipid metabolism where the use of stable isotopes has been more limited. These efforts will benefit from sophisticated radiolabeling reports that continue to enrich our knowledge on lipid biosynthetic pathways and provide some direction for stable isotope experimental design and extension of MFA. Evidence for this assertion is presented through the review of several elegant stable isotope studies and by taking stock of what has been learned from radioisotope investigations when spatial aspects of metabolism were considered. The studies emphasize that glycerolipid production occurs across several locations with assembly of lipids in the ER or plastid, fatty acid biosynthesis occurring in the plastid, and the generation of acetyl-CoA and glycerol-3 phosphate taking place at multiple sites. Considering metabolism in this context underscores the cellular and subcellular organization that is important to enhanced production of glycerolipids in plants. An attempt is made to unify salient features from a number of reports into a diagrammatic model of lipid metabolism and propose where stable isotope labeling experiments and further flux analysis may help address questions in the field. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID- 27003251 TI - Vitamin D supplement improved testicular function in diabetic rats. AB - This study was designed to investigate the role that 1,25(OH)2D3 plays against testicular lesion in diabetic rats and try to find its possible mechanism of the steroidogenesis and the spermatogenesis. In diabetic rats, prolonged hyperglycemia evaluated inflammatory cytokines, damaged sperm production function and redox balance, diminished serum testosterone. After treated with 1,25(OH)2D3 at two different doses respectively for 12 months, all the alternations were effectively normalized. 1,25(OH)2D3 showed inhibitory effect on excessive inflammatory biomarkers and adjusted the expression reproductive genes and testicular androgen synthesis. It also upregulated Bcl-2 expression, decreased Bax and COX-2 expression and inhibited active caspase cascade (caspase 8 and caspase 3), which may preserved the testicular cells under diabetic condition. It revealed that vitamin D supplement may protect the cells through suppressing inflammation factors and alleviating cell apoptotic death, as well as upregulating the expression of genes related to reproductive and testosterone synthesis. PMID- 27003252 TI - TRPV4 is endogenously expressed in vertebrate spermatozoa and regulates intracellular calcium in human sperm. AB - Transient Receptor Potential Vanilloid sub-type 4 (TRPV4) is a non-selective cationic channel involved in regulation of temperature, osmolality and different ligand-dependent Ca(2+)-influx. Recently, we have demonstrated that TRPV4 is conserved in all vertebrates. Now we demonstrate that TRPV4 is endogenously expressed in all vertebrate sperm cells ranging from fish to mammals. In human sperm, TRPV4 is present as N-glycosylated protein and its activation induces Ca(2+)-influx. Its expression and localization differs in swim-up and swim-down cells suggesting that TRPV4 is an important determining factor for sperm motility. We demonstrate that pharmacological activation or inhibition of TRPV4 regulates Ca(2+)-wave propagation from head to tail. Such findings may have wide application in male fertility-infertility, contraception and conservation of endangered species as well. PMID- 27003253 TI - Involvement of ribosomal protein L6 in assembly of functional 50S ribosomal subunit in Escherichia coli cells. AB - Ribosomal protein L6, an essential component of the large (50S) subunit, primarily binds to helix 97 of 23S rRNA and locates near the sarcin/ricin loop of helix 95 that directly interacts with GTPase translation factors. Although L6 is believed to play important roles in factor-dependent ribosomal function, crucial biochemical evidence for this hypothesis has not been obtained. We constructed and characterized an Escherichia coli mutant bearing a chromosomal L6 gene (rplF) disruption and carrying a plasmid with an arabinose-inducible L6 gene. Although this DeltaL6 mutant grew more slowly than its wild-type parent, it proliferated in the presence of arabinose. Interestingly, cell growth in the absence of arabinose was biphasic. Early growth lasted only a few generations (LI-phase) and was followed by a suspension of growth for several hours (S-phase). This suspension was followed by a second growth phase (LII-phase). Cells harvested at both LI- and S-phases contained ribosomes with reduced factor-dependent GTPase activity and accumulated 50S subunit precursors (45S particles). The 45S particles completely lacked L6. Complete 50S subunits containing L6 were observed in all growth phases regardless of the L6-depleted condition, implying that the DeltaL6 mutant escaped death because of a leaky expression of L6 from the complementing plasmid. We conclude that L6 is essential for the assembly of functional 50S subunits at the late stage. We thus established conditions for the isolation of L6-depleted 50S subunits, which are essential to study the role of L6 in translation. PMID- 27003254 TI - PNMA2 mediates heterodimeric interactions and antagonizes chemo-sensitizing activities mediated by members of PNMA family. AB - PNMA2, a member of the Paraneoplastic Ma Family (PNMA), was identified through expression cloning by using anti-sera from patients with paraneoplastic disorder. Tissue expression studies showed that PNMA2 was predominantly expressed in normal human brain; however, the protein was shown to exhibit abnormal expression profile as it was found to be expressed in a number of tumour tissues obtained from paraneopalstic patients. The abnormal expression profile of PNMA2 suggests that it might play an important role in tumorigenesis; however, apart from protein expression and immunological studies, the physiological role of PNMA2 remains unclear. In order to determine potential role of PNMA2 in tumorigenesis, and its functional relationship with PNMA family members, MOAP-1 (PNMA4) and PNMA1, expression constructs encoding the respective proteins were generated for both in vitro and in vivo studies. Our investigations showed that over-expressed MOAP-1 and PNMA1 promoted apoptosis and chemo-sensitization in MCF-7 cells as evidenced by condensed nuclei and Annexin-V positive MCF-7 cells; however, the effects mediated by these proteins were significantly inhibited or abolished when co-expressed with PNMA2 in MCF-7 cells. Furthermore, co-immunoprecipitation study showed that PNMA1 and MOAP-1 failed to associate with each other but readily formed respective heterodimer with PNMA2, suggesting that PNMA2 functions as antagonist of MOAP-1 and PNMA1 through heterodimeric interaction. PMID- 27003255 TI - MiR-30a-5p/UBE3C axis regulates breast cancer cell proliferation and migration. AB - Aberrant expression of ubiquitin Protein ligase E3C (UBE3C) has been documented in breast cancer (BC). MicroRNAs (miRNAs) were shown to play an important role in the regulation of tumor properties in BC. However, whether miRNAs contributes to UBE3C expression in BC cells remains poorly understood. In this study, we report that UBE3C was a direct target of miR-30a-5p. Expression of miR-30a-5p in BC cells reduced UBE3C expression. MCF-7 and MDA-MB-453 cells were transfected miR 30a-5p-overexpression, and found that cell proliferation and migration were inhibited. In contrast, when miR-30a-5p inhibitor were transfected into MCF-7 and MDA-MB-453 cells, cell proliferation and migration were promoted. We study demonstrated that upregulation of miR-30a-5p was significantly suppressed levels of cyclin B1, cyclin D1 and c-myc. Moreover, Correlation analysis indicated that expression of miR-30a-5p was highly negatively correlated with UBE3C, which was upregulated in BC specimens. These data highlight the important role of miR-30a 5p/UBE3C axis in BC development and progression. Therefore, miR-30a-5p activation or UBE3C inhibition may be provide a novel strategy for the treatment of BC. PMID- 27003256 TI - Rhein triggers apoptosis via induction of endoplasmic reticulum stress, caspase-4 and intracellular calcium in primary human hepatic HL-7702 cells. AB - Rhein is an active component of rhubarb; a traditional Chinese medicine reported to induce apoptosis and cause liver toxicity. However, rhein's apoptotic-inducing effects, as well as its molecular mechanisms of action on hepatic cells need to be further explored. In the present study, rhein was found to trigger apoptosis in primary human hepatic HL-7702 cells as showed by annexin V/PI double staining assay and nuclear morphological changes demonstrated by Hoechst 33258 staining. Moreover, it was observed that the mechanism implicated in rhein-induced apoptosis was caspase-dependent, presumably via ER-stress associated pathways, as illustrated by up-regulation of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), C-Jun N-terminal kinase (JNK) and CCAAT/enhancer-binding protein homologous protein (CHOP). Meanwhile, caspase-4 as a hallmark of ER stress, was also showed to be activated following by caspase-3 activation. Furthermore, rhein also promoted intracellular elevation of calcium that contributed in apoptosis induction. Interestingly, pre-treatment with calpain inhibitor I reduced the effects of rhein on apoptosis induction and JNK activation. These data suggested that rhein-induced apoptosis through ER-stress and elevated intracellular calcium level in HL-7702 cells. PMID- 27003257 TI - Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity. AB - Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC 1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer. PMID- 27003259 TI - Imiquimod induces ER stress and Ca(2+) influx independently of TLR7 and TLR8. AB - Endoplasmic reticulum (ER) stress is a physiological response to protein overload or misfolded proteins in the ER. Certain anti-cancer drugs, e.g. bortezomib and nelfinavir, induce ER stress implying that this could be a successful therapeutic strategy against several forms of cancer. To find novel ER-stress inducers we screened a panel of natural and synthetic Toll-like receptor (TLR) agonists against human keratinocytes and identified the anti-cancer drug imiquimod (IMQ) as a potent inducer of ER stress. Other TLR7 and TLR8 agonists, including resiquimod and gardiquimod, did not induce ER stress, demonstrating that IMQ induces ER stress independently of TLR7 and TLR8. We further confirmed this by showing that IMQ could still induce ER stress in mouse Tlr7(-/-) cells. IMQ also induced a rapid and transient influx of extracellular Ca(2+) together with the release of Ca(2+) from internal stores. Depletion of Ca(2+) from the ER is a known cause of ER stress suggesting that IMQ induces ER stress via depletion of ER Ca(2+). The ER-stress inducing property of IMQ is possibly of importance for its efficacy in treating basal cell carcinoma, in situ melanoma, and squamous cell carcinoma. Our data could potentially be harnessed for rational design of even more potent ER-stress inducers and new anti-cancer drugs. PMID- 27003258 TI - HBsAg blocks TYPE I IFN induced up-regulation of A3G through inhibition of STAT3. AB - Interferon (IFN) is a regularly utilized therapeutic for the treatment of chronic hepatitis B and appears to induce superior HBeAg seroconversion comparing nucleos/tide analogs. However, the mechanisms underlying IFN inhibition of HBV replication, as well as poor responses to IFN are unclear. Apobec3G has been reported to be involved in regulating HBV replication. In this study, we investigated Apobec3G expression and regulatory pathways during HBV infection. We show that over-expression of A3G leads to inhibition of HBV replication. We also show that IFN induces a significant increase in A3G protein expression, which is associated with STAT3 activation. We further show that A3G expression in HBV patients is lower compared to non-infected controls, possibly by HBsAg which inhibits IFN induced A3G up-regulation in a dose dependent manner. This process is likely mediated through inhibition of STAT3-Ser727 phosphorylation. The results presented in this study indicate that STAT3 plays an important role in IFN-induced A3G production, and HBsAg may correlated with poor response to IFN treatment. PMID- 27003260 TI - Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. AB - Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. PMID- 27003261 TI - PAK1 translocates into nucleus in response to prolactin but not to estrogen. AB - Tyrosyl phosphorylation of the p21-activated serine-threonine kinase 1 (PAK1) has an essential role in regulating PAK1 functions in breast cancer cells. We previously demonstrated that PAK1 serves as a common node for estrogen (E2)- and prolactin (PRL)-dependent pathways. We hypothesize herein that intracellular localization of PAK1 is affected by PRL and E2 treatments differently. We demonstrate by immunocytochemical analysis that PAK1 nuclear translocation is ligand-dependent: only PRL but not E2 stimulated PAK1 nuclear translocation. Tyrosyl phosphorylation of PAK1 is essential for this nuclear translocation because phospho-tyrosyl-deficient PAK1 Y3F mutant is retained in the cytoplasm in response to PRL. We confirmed these data by Western blot analysis of subcellular fractions. In 30 min of PRL treatment, only 48% of pTyr-PAK1 is retained in the cytoplasm of PAK1 WT clone while 52% re-distributes into the nucleus and pTyr PAK1 shuttles back to the cytoplasm by 60 min of PRL treatment. In contrast, PAK1 Y3F is retained in the cytoplasm. E2 treatment causes nuclear translocation of neither PAK1 WT nor PAK1 Y3F. Finally, we show by an in vitro kinase assay that PRL but not E2 stimulates PAK1 kinase activity in the nuclear fraction. Thus, PAK1 nuclear translocation is ligand-dependent: PRL activates PAK1 and induces translocation of activated pTyr-PAK1 into nucleus while E2 activates pTyr-PAK1 only in the cytoplasm. PMID- 27003262 TI - California mussels (Mytilus californianus) as sentinels for marine contamination with Sarcocystis neurona. AB - Sarcocystis neurona is a terrestrial parasite that can cause fatal encephalitis in the endangered Southern sea otter (Enhydra lutris nereis). To date, neither risk factors associated with marine contamination nor the route of S. neurona infection to marine mammals has been described. This study evaluated coastal S. neurona contamination using California mussels (Mytilus californianus) as sentinels for pathogen pollution. A field investigation was designed to test the hypotheses that (1) mussels can serve as sentinels for S. neurona contamination, and (2) S. neurona contamination in mussels would be highest during the rainy season and in mussels collected near freshwater. Initial validation of molecular assays through sporocyst spiking experiments revealed the ITS-1500 assay to be most sensitive for detection of S. neurona, consistently yielding parasite amplification at concentrations ?5 sporocysts/1 mL mussel haemolymph. Assays were then applied on 959 wild-caught mussels, with detection of S. neurona confirmed using sequence analysis in three mussels. Validated molecular assays for S. neurona detection in mussels provide a novel toolset for investigating marine contamination with this parasite, while confirmation of S. neurona in wild mussels suggests that uptake by invertebrates may serve as a route of transmission to susceptible marine animals. PMID- 27003263 TI - Things happen: Individuals with high obsessive-compulsive tendencies omit agency in their spoken language. AB - The study examined the prediction that obsessive-compulsive tendencies are related to an attenuated sense of agency (SoA). As most explicit agency judgments are likely to reflect also motivation for and expectation of control, we examined agency in sentence production. Reduced agency can be expressed linguistically by omitting the agent or by using grammatical framings that detach the event from the entity that caused it. We examined the use of agentic language of participants with high vs. low scores on a measure of obsessive-compulsive (OC) symptoms, using structured linguistic tasks in which sentences are elicited in a conversation-like setting. As predicted, high OC individuals produced significantly more non-agentic sentences than low OC individuals, using various linguistic strategies. The results suggest that OC tendencies are related to attenuated SoA. We discuss the implications of these findings for explicating the SoA in OCD and the potential contribution of language analysis for understanding psychopathology. PMID- 27003264 TI - Altered states of consciousness are related to higher sexual responsiveness. AB - Altered states of consciousness lead to profound changes in the sense of self, time and space. We assessed how these changes were related to sexual responsiveness during sex. 116 subjects reported (a) intensity of awareness concerning body, space and time, and (b) satisfaction, desire, arousal, and orgasm occurrence. We differentiated vaginal intercourse orgasm from noncoital orgasm. Female vaginal intercourse orgasm was further differentiated as with or without concurrent clitoral masturbation. Overall, sexual responsiveness was related to greater body awareness and lesser time and space awareness. Satisfaction, desire, and arousal were especially associated with less time awareness in women. Female orgasms during vaginal intercourse were related to greater body awareness and lesser time awareness, but noncoital orgasms were unrelated. Our findings provide empirical support for the hypotheses that altered states of consciousness with attentional absorption are strongly related to sexual responsiveness in women, and to a lesser extent in men. PMID- 27003265 TI - Vantage perspective during encoding: The effects on phenomenological memory characteristics. AB - The vantage perspective from which a memory is retrieved influences the memory's emotional impact, intrusiveness, and phenomenological characteristics. This study tested whether similar effects are observed when participants were instructed to imagine the events from a specific perspective. Fifty student participants listened to a verbal report of car-accidents and visualized the scenery from either a field or observer perspective. There were no between-condition differences in emotionality of memories and the number of intrusions, but imagery experienced from a relative observer perspective was rated as less self-relevant. In contrast to earlier studies on memory retrieval, vantage perspective influenced phenomenological memory characteristics of the memory representation such as sensory details, and ratings of vividness and distancing of the memory. However, vantage perspective is most likely not a stable phenomenological characteristic itself. Implications and suggestions for future research are discussed. PMID- 27003266 TI - Current practice of preconception care by primary caregivers in the Netherlands. AB - OBJECTIVES: Over the past decade the value of preconception care (PCC) consultations has been acknowledged. Investments have been made to promote delivery and uptake of PCC consultations in the Dutch primary care setting. We assessed current activities, perceptions and prerequisites for delivery of PCC in primary care. METHODS: A questionnaire was compiled and distributed by mail or e mail among 1682 general practitioners (GPs) and 746 midwives in the Netherlands between 2013 and 2014. RESULTS: The questionnaire was completed by 449 GPs and 250 midwives. While GPs and midwives were frequently asked about preconception risks, explicit requests by patients for a PCC consultation were less frequent. Although caregivers gave information on preconception risk factors, only a minority recommended PCC in the form of a dedicated consultation. Such consultations occurred infrequently. Risk factor assessment varied between GPs and midwives. Respondents' perceptions of PCC consultations, however, were generally positive. A small proportion believed that PCC medicalised pregnancy, and recognised barriers in actively raising the topic of patients' pregnancy wishes. More training, staff, promotion of PCC and adequate reimbursement were prerequisites for future delivery. GPs differed in their opinion of whether they or midwives were primarily responsible for PCC consultations. Midwives, however, saw themselves as responsible for providing PCC consultations. CONCLUSIONS: Primary care is underserving prospective parents with regards to PCC consultations. Targets to increase delivery of systematic PCC are: (1) promotion during routine care; (2) increased use of tools; (3) increased collaboration among primary caregivers; (4) reduction of caregivers' negative perceptions; and (5) tailoring PCC consultations to suit women's preferences. PMID- 27003267 TI - An inducible tool for random mutagenesis in Aspergillus niger based on the transposon Vader. AB - The ascomycete Aspergillus niger is widely used in the biotechnology, for instance in producing most of the world's citric acid. It is also known as a major food and feed contaminant. While generation of gene knockouts for functional genomics has become feasible in ku70 mutants, analyzing gene functions or metabolic pathways remains a laborious task. An unbiased transposon-based mutagenesis approach may aid this process of analyzing gene functions by providing mutant libraries in a short time. The Vader transposon is a non autonomous DNA-transposon, which is activated by the homologous tan1-transposase. However, in the most commonly used lab strain of A. niger (N400 strain and derivatives), we found that the transposase, encoded by the tan1 gene, is mutated and inactive. To establish a Vader transposon-based mutagenesis system in the N400 background, we expressed the functional transposase of A. niger strain CBS 513.88 under the control of an inducible promoter based on the Tet-on system, which is activated in the presence of the antibiotic doxycycline (DOX). Increasing amounts of doxycycline lead to higher Vader excision frequencies, whereas little to none activity of Vader was observed without addition of doxycycline. Hence, this system appears to be suitable for producing stable mutants in the A. niger N400 background. PMID- 27003268 TI - Probing phenotypic growth in expanding Bacillus subtilis biofilms. AB - We develop an optical imaging technique for spatially and temporally tracking biofilm growth and the distribution of the main phenotypes of a Bacillus subtilis strain with a triple-fluorescent reporter for motility, matrix production, and sporulation. We develop a calibration procedure for determining the biofilm thickness from the transmission images, which is based on Beer-Lambert's law and involves cross-sectioning of biofilms. To obtain the phenotype distribution, we assume a linear relationship between the number of cells and their fluorescence and determine the best combination of calibration coefficients that matches the total number of cells for all three phenotypes and with the total number of cells from the transmission images. Based on this analysis, we resolve the composition of the biofilm in terms of motile, matrix-producing, sporulating cells and low fluorescent materials which includes matrix and cells that are dead or have low fluorescent gene expression. We take advantage of the circular growth to make kymograph plots of all three phenotypes and the dominant phenotype in terms of radial distance and time. To visualize the nonlocal character of biofilm growth, we also make kymographs using the local colonization time. Our technique is suitable for real-time, noninvasive, quantitative studies of the growth and phenotype distribution of biofilms which are either exposed to different conditions such as biocides, nutrient depletion, dehydration, or waste accumulation. PMID- 27003269 TI - GRE2 from Scheffersomyces stipitis as an aldehyde reductase contributes tolerance to aldehyde inhibitors derived from lignocellulosic biomass. AB - Scheffersomyces (Pichia) stipitis is one of the most promising yeasts for industrial bioethanol production from lignocellulosic biomass. S. stipitis is able to in situ detoxify aldehyde inhibitors (such as furfural and 5 hydroxymethylfurfural (HMF)) to less toxic corresponding alcohols. However, the reduction enzymes involved in this reaction remain largely unknown. In this study, we reported that an uncharacterized open reading frame PICST_72153 (putative GRE2) from S. stipitis was highly induced in response to furfural and HMF stresses. Overexpression of this gene in Saccharomyces cerevisiae improved yeast tolerance to furfural and HMF. GRE2 was identified as an aldehyde reductase which can reduce furfural to FM with either NADH or NADPH as the co-factor and reduce HMF to FDM with NADPH as the co-factor. This enzyme can also reduce multiple aldehydes to their corresponding alcohols. Amino acid sequence analysis indicated that it is a member of the subclass "intermediate" of the short-chain dehydrogenase/reductase (SDR) superfamily. Although GRE2 from S. stipitis is similar to GRE2 from S. cerevisiae in a three-dimensional structure, some differences were predicted. GRE2 from S. stipitis forms loops at D133-E137 and T143-N145 locations with two alpha-helices at E154-K157 and E252-A254 locations, different GRE2 from S. cerevisiae with an alpha-helix at D133-E137 and a beta sheet at T143-N145 locations, and two loops at E154-K157 and E252-A254 locations. This research provided guidelines for the study of other SDR enzymes from S. stipitis and other yeasts on tolerant mechanisms to aldehyde inhibitors derived from lignocellulosic biomass. PMID- 27003270 TI - In-situ biogas sparging enhances the performance of an anaerobic membrane bioreactor (AnMBR) with mesh filter in low-strength wastewater treatment. AB - In the recent years, anaerobic membrane bioreactor (AnMBR) technology is being considered as a very attractive alternative for wastewater treatment due to the striking advantages such as upgraded effluent quality. However, fouling control is still a problem for the application of AnMBR. This study investigated the performance of an AnMBR using mesh filter as support material to treat low strength wastewater via in-situ biogas sparging. It was found that mesh AnMBR exhibited high and stable chemical oxygen demand (COD) removal efficiencies with values of 95 +/- 5 % and an average methane yield of 0.24 L CH4/g CODremoved. Variation of transmembrane pressure (TMP) during operation indicated that mesh fouling was mitigated by in-situ biogas sparging and the fouling rate was comparable to that of aerobic membrane bioreactor with mesh filter reported in previous researches. The fouling layer formed on the mesh exhibited non-uniform structure; the porosity became larger from bottom layer to top layer. Biogas sparging could not change the composition but make thinner thickness of cake layer, which might be benefit for reducing membrane fouling rate. It was also found that ultrasonic cleaning of fouled mesh was able to remove most foulants on the surface or pores. This study demonstrated that in-situ biogas sparging enhanced the performance of AnMBRs with mesh filter in low-strength wastewater treatment. Apparently, AnMBRs with mesh filter can be used as a promising and sustainable technology for wastewater treatment. PMID- 27003272 TI - Are corticosteroids useful in all degrees of severity and rapid recovery of Bell's palsy? AB - Conclusions The results provide preliminary evidence that corticosteroids were not effective in all grades of dysfunction and for achieving a rapid remission in the early phase of BP, highlighting the need to define standard and rigorous criteria to prescribe corticosteroids in these patients. Objectives The main aim of this study was to investigate whether the use of corticosteroids better associated than paralleled with neuromuscular training (C + FNT) is more effective than facial neuromuscular training (FNT) applied alone, in terms of recovery degree and facial symmetry during the early phase of Bell's palsy (BP). Patients and methods A prospective single-blinded study involved 73 patients: the C + FNT group (n = 42; median age = 37.5 years) and FNT group (n = 31; median age = 49.0 years). Patients were assessed before and 6 weeks after treatment by House Brackmann (HB-FGS) and Sunnybrook Facial Grading System (SB-FGS). Results Recovery degree and facial symmetry improved significantly in both groups (p < 0.001), without differences between groups (p > 0.05). However, the C + FNT group displayed better outcomes for cheek (p = 0.004) and mouth (p = 0.022) resting symmetry at SB-FGS, instead of compared to the FNT group. The corticosteroids had no significant effect on all recovery degrees (p = 0.992) and rapid remission (p = 0.952). Multiple linear regression analysis showed that the type of intervention was not a significant predictor for recovery degree (p = 0.917). PMID- 27003271 TI - Predicting Individual Survival After Hepatectomy for Hepatocellular Carcinoma: a Novel Nomogram from the "HCC East & West Study Group". AB - INTRODUCTIONS: Different staging systems have been devised for patients undergoing resection for hepatocellular carcinoma (HCC) with disparate results. The aim of this study was to create a new nomogram to predict individual survival after hepatectomy for HCC. METHODS: Based on the "Hepatocellular Carcinoma: Eastern & Western Experiences Network," data from 2046 patients who underwent HCC resections at ten centers were reviewed. Patient survival was analyzed with Cox regression analysis to construct a unique nomogram and contour plots to predict survival. RESULTS: The nomograms built on the multivariate analyses, which showed that the independent predictors were tumor size, tumor number, vascular invasion, cirrhosis, preoperative bilirubin value, and esophageal varices, showed good calibration and discriminatory abilities with C-index value of 0.62 (95 % CI, 0.59-0.69) and 0.61 (95 % CI, 0.56-0.64) for overall and disease-free survival, respectively. The 5-year survival contour plots showed that the presence of vascular invasion was associated with decreased survival, regardless of the tumor number or size. Cirrhosis and varices were equally associated with decreased survival, according to the tumor number or size. CONCLUSIONS: These nomograms accurately predict individual prognosis after HCC resection and support an expansion of the selection criteria for resection. They offer useful guidance to clinicians for individual survival prediction. PMID- 27003274 TI - Back on the scent: the olfactory system in CNS demyelinating diseases. AB - Olfactory dysfunction is recognised across an ever broadening spectrum of neuropsychiatric conditions including central nervous system (CNS) demyelinating diseases such as multiple sclerosis (MS) and neuromyelitis optica (NMO). In this review, we unravel the striking evidence highlighting how olfactory loss is a common clinical feature in MS and NMO. We provide an overview of the supportive psychophysical, electrophysiological, radiological and pathological data that point to the anatomical substrate of olfactory deficits in these diseases. The pattern of underlying pathology affecting the olfactory system is shown to be complex, involving multiple structures that are affected in different ways throughout the course of the disease. This review is the first to synthesise the expanding body of literature on the topic, provides novel insight into the way in which the olfactory system is affected in CNS demyelinating diseases, and raises intriguing questions about the role of this system in the pathogenesis of these diseases. PMID- 27003273 TI - Phylogeography of Rhipicephalus sanguineus sensu lato and its relationships with climatic factors. AB - Brown dog ticks morphologically identifiable as Rhipicephalus sanguineus sensu lato, are distributed world-wide and their systematics is controversial. Results of genetic and reproductive compatibility studies of geographically distinct populations of R. sanguineus s.l. indicate that the R. sanguineus complex is paraphyletic. To further elucidate systematic relationships within R. sanguineus s.l. and geographic boundaries of its lineages, we conducted a phylogeographical study of 136 tick specimens from 23 countries. Voucher specimens were morphologically identified. A phylogenetic tree was constructed using concatenated partial mitochondrial 12S and 16S rDNA gene sequences and analyzed by the Neighbor-Joining method. A set of 19 bioclimatic variables within the WorldClim dataset were extracted and analyzed to assess correlations between distribution of R. sanguineus s.l. lineages and climatic variables. The following four branches are clearly recognized on the phylogenetic tree: R. sanguineus s.l. tropical and temperate clades, R. leporis, and R. turanicus. DNA sequences of Rhipicephalus ticks from Israel differ from those of other groups. Strong association between geographical locations of major clades of R. sanguineus s.l. and temperature was identified. The tropical clade of R. sanguineus s.l. occupies areas with the annual mean temperature >20 degrees C, whereas the temperate clade is present in areas with the annual mean temperature <20 degrees C. Our results indicate that ticks in two closely related phylogenetic clades are adapted to different environmental conditions and support proposals for re classification of R. sanguineus complex. Differences in R. sanguineus s.l. ecology and human/animal pathogens transmitted by different taxa of brown dog tick need to be studied. PMID- 27003275 TI - Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy). AB - OBJECTIVE: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. METHODS: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. RESULTS: A total of 3492 cases (mean age, 73.0+/-12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. CONCLUSIONS: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions. PMID- 27003276 TI - The value of reasons for encounter in early detection of colorectal cancer. AB - BACKGROUND: Symptoms with a high predictive power for colorectal cancer (CRC) do not exist. OBJECTIVE: To explore the predictive value of patients' reason for encounter (RFE) in the two years prior to the diagnosis of CRC. METHODS: A retrospective nested case-control study using prospectively collected data from electronic records in general practice over 20 years. Matching was done based on age (within two years), gender and practice. The positive likelihood ratios (LR+) and odds ratios (OR) were calculated for RFE between cases and controls in the two years before the index date. RESULTS: We identified 184 CRC cases and matched 366 controls. Six RFEs had significant LR + and ORs for CRC, which may have high predictive power. These RFEs are part of four chapters in the International Classification of Primary Care (ICPC) that include tiredness (significant at 3-6 months prior to the diagnosis; LR+ 2.6 and OR 3.07; and from 0 to 3 months prior to the diagnosis; LR+ 2.0 and OR 2.36), anaemia (significant at three months before diagnosis; LR+ 9.8 and OR 16.54), abdominal pain, rectal bleeding and constipation (significant at 3-6 months before diagnosis; LR+ 3.0 and OR 3.33; 3 months prior to the diagnosis LR+ 8.0 and OR 18.10) and weight loss (significant at three months before diagnosis; LR+ 14.9 and OR 14.53). CONCLUSION: Data capture and organization in ICPC permits study of the predictive value of RFE for CRC in primary care. PMID- 27003277 TI - Impact of surgeon-defined capsular incision during radical prostatectomy on biochemical recurrence rates. AB - PURPOSE: To determine the impact of intraoperative surgeon-defined incision of the prostatic capsule (CapI) on cancer recurrence and to give an overview of the different definitions of CapI. CapI during radical prostatectomy (RP) occurs in a non-negligible number of patients; still, its impact on biochemical recurrence (BCR) remains controversial as definition of CapI differs in literature. METHODS: We analyzed the data of 3253 consecutive RP between 2009 and 2011. Occurrence and side of intraoperative CapI was documented by the surgeon. Factors influencing CapI were addressed using logistic regressions. The impact of CapI on BCR was analyzed using Cox regressions including traditional prognosticators. RESULTS: Median follow-up was 36.2 months. Unilateral (bilateral) CapI occurred in 22.2 % (12.1 %) of patients. CapI was reported more often following open RP (p < 0.0001) and nerve-sparing procedure (p = 0.0004). Three-year BCR-free survival was 78.8, 79.9 and 82.1 % (p = 0.13) for patients with no, unilateral and bilateral CapI. In multivariate analysis, pT-stage (p < 0.0001), Gleason grade (p < 0.0005) and nodal status (p < 0.0005) were significantly associated with BCR. However, CapI had no independent impact on BCR (unilateral vs. no CapI, p = 0.55, bilateral vs. no CapI, p = 0.32). CONCLUSIONS: Intraoperative CapI occurs in a relevant number of RP and is more frequent during nerve-sparing procedure and open RP. However, there seems to be no impact of CapI and its extent on the incidence of early BCR. PMID- 27003278 TI - Bonding effectiveness and multi-interfacial characterization of two direct buildup resin core systems bonded to post-space dentin. AB - OBJECTIVES: The aim of the present study was to evaluate the bonding effectiveness of two resin core buildup systems using conventional methods in the field of adhesive dentistry and a new non-destructive method. MATERIALS AND METHODS: Twenty-four single-rooted human teeth were built up with dual-cure one step self-etch adhesive and composite systems (SY1: Clearfil DC bond and Clearfil DC core automix, SY2: Clearfil bond SE one and Clearfil DC core automix one). The prepared samples were sectioned into approximately 1 * 1-mm-thick beams and subjected to micro-tensile bond strength (MUTBS) testing (n = 24). The fractured beams after MUTBS testing were analyzed by SEM and energy-dispersive X-ray (EDX) spectrometry. The three teeth filled with each resin core system were sectioned and embedded in epoxy resin to observe the dentin-bonding interface under TEM (n = 6). Moreover, three of each resin core-filled teeth without any processing were examined using MUCT (n = 6). RESULTS: Two-way ANOVA revealed that the two factors "root region" (p < 0.001, F = 15.22) and "system" (SY1 < SY2; p < 0.001, F = 22.52) had a significant influence. The MUTBS gradually decreased from the coronal side to the apical side of the root canal. Morphological evaluation revealed that SY2 was superior in terms of resin curing at the apical side. MUCT non-destructive evaluation clearly revealed gap formation in SY1. CONCLUSION: SY2, which included a new light-independent catalyst, showed better bonding effectiveness and adhesive interface to dentin compared to that of SY1. CLINICAL RELEVANCE: The new catalyst, which is activated by contact with adhesive and resin composite, can be used for resin core buildup restorations. PMID- 27003279 TI - Effect of light and nutrient availability on the release of dissolved organic carbon (DOC) by Caribbean turf algae. AB - Turf algae increasingly dominate benthic communities on coral reefs. Given their abundance and high dissolved organic carbon (DOC) release rates, turf algae are considered important contributors to the DOC pool on modern reefs. The release of photosynthetically fixed carbon as DOC generally, but not always, increases with increased light availability. Nutrient availability was proposed as an additional factor to explain these conflicting observations. To address this proposed but untested hypothesis, we documented the interactive contributions of light and nutrient availability on the release of DOC by turf algae. DOC release rates and oxygen production were quantified in incubation experiments at two light levels (full and reduced light) and two nutrient treatments (natural seawater and enriched seawater). In natural seawater, DOC release at full light was four times higher than at reduced light. When nutrients were added, DOC release rates at both light levels were similar to the natural seawater treatment at full light. Our results therefore show that low light in combination with low nutrient availability reduces the release of DOC by turf algae and that light and nutrient availability interactively determine DOC release rates by this important component of Caribbean reef communities. PMID- 27003280 TI - Prognostic models for prediction of outcomes after traumatic brain injury based on patients admission characteristics. AB - OBJECTIVE: To identify the best performing prognostic model using admission characteristics to predict mortality at 30 days and functioning outcome at 6 months post-admission in patients with moderate or severe brain injury. METHODS: Using a retrospective database (n = 1466 patients) of a tertiary trauma care centre, three different models were developed using logistic regression methods for predicting mortality and functioning outcome. The performance of the models was assessed in terms of discrimination and calibration. The models were validated using split sample method. For facilitating clinical usefulness, score charts were derived from the regression models. RESULTS: The variables motor score, hypotension, pupillary reactivity, age, creatinine level, limb movement (hemiparesis), and tSAH/IVH were found to be the most predictive independent prognostic factors of both mortality and functioning outcome. For both the outcomes, discriminative ability of the three prognostic models was excellent in the development dataset (AUC = 0.845--0.905) as well as the validation data set (AUC = 0.836-0.880). Calibration in the validation data set for model-2 was good (H-L test p-value > 0.05); however, for model-1 and model-3, it was poor (H-L test p-value < 0.05). CONCLUSION: For clinical decision-making, model-2 is recommended on the basis of good performance in predicting outcomes in patients with moderate or severe TBI in India and other similar countries. PMID- 27003281 TI - Production of Poly (3-Hydroxybutyric Acid) by Ralstonia eutropha in a Biocalorimeter and its Thermokinetic Studies. AB - Bioplastic production from microbial sources is an emerging area which provides opportunities even to convert the wastes into bioplastics. Poly (3-hydroxybutyric acid), commonly called as PHB, is a bioplastic, which is stored as intracellular cytoplasmic inclusions in microorganisms. The objectives of this study are to calorimetrically monitor the PHB production and evaluate the thermokinetic data in a bioreaction calorimeter (BioRC1e). Thus, a well-known PHB-producing bacteria Ralstonia eutropha was selected for batch process in a bioreaction calorimeter. The metabolic heat generated was found to be correlated with the biomass, substrate consumption, oxygen uptake rate (OUR), carbon dioxide evolution rate (CER) and PHB production. The OUR pattern explained the oxidative metabolism of the strain R. eutropha. The heat yields due to biomass and glucose consumption during PHB production were found to be 12.56 and 13.56 kJ/g, respectively. The oxycalorific value obtained for the PHB production was 443.80 kJ/mol of O2. The concentration of PHB obtained in BioRC1e was 4.33 g/L with a production rate of 0.09 g/L/h. The chemical structure of the extracted PHB by R. eutropha was confirmed using fourier transform infrared spectroscopy (FT-IR) and (1)H and (13)C nuclear magnetic resonance (NMR) analysis. PMID- 27003282 TI - Optimization of the Production of Inactivated Clostridium novyi Type B Vaccine Using Computational Intelligence Techniques. AB - Clostridium novyi causes necrotic hepatitis in sheep and cattle, as well as gas gangrene. The microorganism is strictly anaerobic, fastidious, and difficult to cultivate in industrial scale. C. novyi type B produces alpha and beta toxins, with the alpha toxin being linked to the presence of specific bacteriophages. The main strategy to combat diseases caused by C. novyi is vaccination, employing vaccines produced with toxoids or with toxoids and bacterins. In order to identify culture medium components and concentrations that maximized cell density and alpha toxin production, a neuro-fuzzy algorithm was applied to predict the yields of the fermentation process for production of C. novyi type B, within a global search procedure using the simulated annealing technique. Maximizing cell density and toxin production is a multi-objective optimization problem and could be treated by a Pareto approach. Nevertheless, the approach chosen here was a step-by-step one. The optimum values obtained with this approach were validated in laboratory scale, and the results were used to reload the data matrix for re parameterization of the neuro-fuzzy model, which was implemented for a final optimization step with regards to the alpha toxin productivity. With this methodology, a threefold increase of alpha toxin could be achieved. PMID- 27003283 TI - Physicochemical Properties and Storage Stability of Microencapsulated DHA-Rich Oil with Different Wall Materials. AB - This study aimed to evaluate the physicochemical properties and storage stability of microencapsulated DHA-rich oil spray dried with different wall materials: model 1 (modified starch, gum arabic, and maltodextrin), model 2 (soy protein isolate, gum arabic, and maltodextrin), and model 3 (casein, glucose, and lactose). The results indicated that model 3 exhibited the highest microencapsulation efficiency (98.66 %) and emulsion stability (>99 %), with a moisture content and mean particle size of 1.663 % and 14.173 MUm, respectively. Differential scanning calorimetry analysis indicated that the Tm of DHA-rich oil microcapsules was high, suggesting that the entire structure of the microcapsules remained stable during thermal processing. A thermogravimetric analysis curve showed that the product lost 5 % of its weight at 172 degrees C and the wall material started to degrade at 236 degrees C. The peroxide value of microencapsulated DHA-rich oil remained at one ninth after accelerated oxidation at 45 degrees C for 8 weeks to that of the unencapsulated DHA-rich oil, thus revealing the promising oxidation stability of DHA-rich oil in microcapsules. PMID- 27003284 TI - Positive anomalous concentrations of Pb in some gabbroic rocks of Afikpo basin southeastern Nigeria. AB - Gabbroic rocks have intruded the sedimentary sequence at Ameta in Afikpo basin southeastern Nigeria. Petrographic and geochemical features of the rocks were studied in order to evaluate their genetic and geotectonic history. The petrographic results show that the rocks contain plagioclase, olivine, pyroxene, biotite, iron oxide, and traces of quartz in three samples. Major element characteristics show that the rocks are subalkaline. In addition, the rocks have geochemical characteristics similar to basaltic andesites. The trace elements results show inconsistent concentrations of high field strength elements (Zr, Nb, Th, Ta), moderate enrichment of large-ion lithophile elements (Rb, Sr, Ba) and low concentrations of Ni and Cr. Rare earth element results show that the rocks are characterized by enrichment of light rare earth elements, middle rare earth elements enrichment, and depletion of heavy rare earth elements with slight positive europium anomalies. Zinc concentrations are within the normal range in basaltic rocks. There are extremely high concentrations of Pb in three of the rock samples. The high Pb concentrations in some of these rocks could be as a result of last episodes of magmatic crystallization. The rocks intruded the Asu River Group; organic components in the sedimentary sequence probably contain Pb which has been assimilated into the magma at the evolutionary stage of the magma. Weathering of some rocks that contain galena could lead to an increase in the concentration of lead in the gabbroic rocks, especially when the migration and crystallization of magma take place in an aqueous environment. Nevertheless, high concentration of lead is hazardous to health and environment. PMID- 27003285 TI - Interleukin-12 inhibits the hepatocellular carcinoma growth by inducing macrophage polarization to the M1-like phenotype through downregulation of Stat 3. AB - Hepatocellular carcinoma is the third most common cause of cancer death worldwide. Novel early detection biomarkers and efficacious therapy strategies are needed. Macrophages recruited from circulation monocytes are the major component of solid cancer and play an important role in the carcinogenesis. Whether overexpression of L-12 in monocytes could induce the phenotype directional differentiation into tumoricidal M1 macrophages and inhibit HCC growth in tumor microenvironment was investigated in this study. For the establishment of the monocyte/IL-12 and polarization of M1-like macrophage, the IL-12 overexpressing recombinant monocyte/IL-12 cells were established by infecting with pAd5F35-CMV/IL-12 adenovirus and co-cultured with HCC SMMC-7721 and Hep3B cells. It was found that the phenotype of monocyte/IL-12 polarized to M1-like macrophages with CD197high IL-12high CD206low IL-10low, and decreased expression of TGF-beta, VEGF-A, and MMP-9. In order to explore the mechanism underlying the macrophages polarization, we detected the Stat-3 pathway and its downstream transcription factor c-myc, and found that the p-Stat-3 and c-myc were down-regulated. To evaluate the effects of monocyte/IL-12 on inhibiting HCC growth, various assays including CCK8, flow cytometry, colony-forming and Transwell assays in vitro, and xenograft mouse models and immunohistochemical analyses in vivo were used to detect the HCC growth and relative markers. Treated with IL-12 overexpressing monocytes, the xenograft tumor growth was significantly inhibited in vivo. These results have proven that IL-12-overexpressed monocytes could directionally differentiate to M1-like macrophages through downregulation of Stat-3 and result in the inhibition of HCC growth. PMID- 27003286 TI - Haldane and Mayr: a response to Rao and Nanjundiah. AB - The discussion with Rao and Nanjundiah about the history of interactions between J. B. S. Haldane and Ernst Mayr is further extended in this note. The nature of the dispute about beanbag genetics is explicated as consisting of two separate issues, one about the role of mathematical analysis in evolutionary biology, and the other about the value of single-locus genic models. PMID- 27003287 TI - OXA-Carbapenemases Present in Clinical Acinetobacter baumannii-calcoaceticus Complex Isolates from Patients in Kurdistan Region, Iraq. AB - In addition to intrinsic resistance in Acinetobacter baumannii, many different types of acquired resistance mechanisms have been reported, including the presence of VIM and IMP metallo beta-lactamases and also of blaOXA-23-like and blaOXA-58-like enzymes. In the Kurdistan region of Iraq, the multiresistant A. baumannii-calcoaceticus complex is prevalent. We characterized the different mechanisms of resistance present in clinical isolates collected from different wards and different hospitals from the Kurdistan region. One hundred twenty clinical nonduplicate A. baumannii-calcoaceticus complex isolates were collected from four hospitals between January 2012 and October 2013. The identification of the isolates was confirmed by MALDI-TOF. The susceptibility to different antibiotics was determined by disk diffusion and analyzed in accordance to EUCAST guidelines. By PCR, the presence of blaOXA-51-like, blaOXA-23-like, blaOXA-24 like, and blaOXA-58-like genes was determined as well as the presence of the insertion element ISAba1. Clonal diversity was analyzed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme ApaI and, in addition, multilocus sequence typing (MLST) was performed on a selected subset of 15 isolates. All 120 A. baumannii isolates harbored blaOXA-51-like genes. One hundred one out of 110 (92%) imipenem (IMP)-resistant A. baumannii-calcoaceticus complex isolates additionally carried the blaOXA-23-like gene and four isolates (3%) were positive for blaOXA-24-like. All 101 blaOXA-23-like-positive isolates had the ISAba1 insertion sequence, 1,600 bp upstream of the blaOXA-23-like gene. The blaOXA-58-like gene was not detected in any of the 110 IMP-resistant strains. Eight different PFGE clusters were identified and distributed over the different hospitals. MLST analysis performed on a subset of 15 representative isolates revealed the presence of the international clone ST2 (Pasteur). Besides ST2 (Pasteur), also many other STs (Pasteur) were encountered such as ST136, ST94, ST623, ST792, and ST793, all carrying the blaOXA-23 gene. In clinical A. baumannii-calcoaceticus complex isolates from Kurdistan-Iraq, the blaOXA-23 gene in combination with the upstream ISAba1 insertion element is largely responsible for carbapenem resistance. Several small clusters of identical genotypes were found from patients admitted to the same ward and during overlapping time periods, suggesting transmission within the hospital. Identification of source(s) and limiting the transmission of these strains to patients needs to be prioritized. PMID- 27003288 TI - Meta-analytic connectivity modeling of the human superior temporal sulcus. AB - The superior temporal sulcus (STS) is a critical region for multiple neural processes in the human brain Hein and Knight (J Cogn Neurosci 20(12): 2125-2136, 2008). To better understand the multiple functions of the STS it would be useful to know more about its consistent functional coactivations with other brain regions. We used the meta-analytic connectivity modeling technique to determine consistent functional coactivation patterns across experiments and behaviors associated with bilateral anterior, middle, and posterior anatomical STS subregions. Based on prevailing models for the cortical organization of audition and language, we broadly hypothesized that across various behaviors the posterior STS (pSTS) would coactivate with dorsal-stream regions, whereas the anterior STS (aSTS) would coactivate with ventral-stream regions. The results revealed distinct coactivation patterns for each STS subregion, with some overlap in the frontal and temporal areas, and generally similar coactivation patterns for the left and right STS. Quantitative comparison of STS subregion coactivation maps demonstrated that the pSTS coactivated more strongly than other STS subregions in the same hemisphere with dorsal-stream regions, such as the inferior parietal lobule (only left pSTS), homotopic pSTS, precentral gyrus and supplementary motor area. In contrast, the aSTS showed more coactivation with some ventral-stream regions, such as the homotopic anterior temporal cortex and left inferior frontal gyrus, pars orbitalis (only right aSTS). These findings demonstrate consistent coactivation maps across experiments and behaviors for different anatomical STS subregions, which may help future studies consider various STS functions in the broader context of generalized coactivations for individuals with and without neurological disorders. PMID- 27003289 TI - Evolutionary genomics of epidemic visceral leishmaniasis in the Indian subcontinent. AB - Leishmania donovani causes visceral leishmaniasis (VL), the second most deadly vector-borne parasitic disease. A recent epidemic in the Indian subcontinent (ISC) caused up to 80% of global VL and over 30,000 deaths per year. Resistance against antimonial drugs has probably been a contributing factor in the persistence of this epidemic. Here we use whole genome sequences from 204 clinical isolates to track the evolution and epidemiology of L. donovani from the ISC. We identify independent radiations that have emerged since a bottleneck coincident with 1960s DDT spraying campaigns. A genetically distinct population frequently resistant to antimonials has a two base-pair insertion in the aquaglyceroporin gene LdAQP1 that prevents the transport of trivalent antimonials. We find evidence of genetic exchange between ISC populations, and show that the mutation in LdAQP1 has spread by recombination. Our results reveal the complexity of L. donovani evolution in the ISC in response to drug treatment. PMID- 27003290 TI - A glucose-starvation response regulates the diffusion of macromolecules. AB - The organization and biophysical properties of the cytosol implicitly govern molecular interactions within cells. However, little is known about mechanisms by which cells regulate cytosolic properties and intracellular diffusion rates. Here, we demonstrate that the intracellular environment of budding yeast undertakes a startling transition upon glucose starvation in which macromolecular mobility is dramatically restricted, reducing the movement of both chromatin in the nucleus and mRNPs in the cytoplasm. This confinement cannot be explained by an ATP decrease or the physiological drop in intracellular pH. Rather, our results suggest that the regulation of diffusional mobility is induced by a reduction in cell volume and subsequent increase in molecular crowding which severely alters the biophysical properties of the intracellular environment. A similar response can be observed in fission yeast and bacteria. This reveals a novel mechanism by which cells globally alter their properties to establish a unique homeostasis during starvation. PMID- 27003291 TI - A novel biosensor to study cAMP dynamics in cilia and flagella. AB - The cellular messenger cAMP regulates multiple cellular functions, including signaling in cilia and flagella. The cAMP dynamics in these subcellular compartments are ill-defined. We introduce a novel FRET-based cAMP biosensor with nanomolar sensitivity that is out of reach for other sensors. To measure cAMP dynamics in the sperm flagellum, we generated transgenic mice and reveal that the hitherto methods determining total cAMP levels do not reflect changes in free cAMP levels. Moreover, cAMP dynamics in the midpiece and principal piece of the flagellum are distinctively different. The sole cAMP source in the flagellum is the soluble adenylate cyclase (SACY). Although bicarbonate-dependent SACY activity requires Ca(2+), basal SACY activity is suppressed by Ca(2+). Finally, we also applied the sensor to primary cilia. Our new cAMP biosensor features unique characteristics that allow gaining new insights into cAMP signaling and unravel the molecular mechanisms underlying ciliary function in vitro and in vivo. PMID- 27003292 TI - A pH-driven transition of the cytoplasm from a fluid- to a solid-like state promotes entry into dormancy. AB - Cells can enter into a dormant state when faced with unfavorable conditions. However, how cells enter into and recover from this state is still poorly understood. Here, we study dormancy in different eukaryotic organisms and find it to be associated with a significant decrease in the mobility of organelles and foreign tracer particles. We show that this reduced mobility is caused by an influx of protons and a marked acidification of the cytoplasm, which leads to widespread macromolecular assembly of proteins and triggers a transition of the cytoplasm to a solid-like state with increased mechanical stability. We further demonstrate that this transition is required for cellular survival under conditions of starvation. Our findings have broad implications for understanding alternative physiological states, such as quiescence and dormancy, and create a new view of the cytoplasm as an adaptable fluid that can reversibly transition into a protective solid-like state. PMID- 27003293 TI - An Engineered Endomorphin-2 Gene for Morphine Withdrawal Syndrome. AB - An optimal therapeutics to manage opioid withdrawal syndrome is desired for opioid addiction treatment. Down-regulation of endogenous endomorphin-2 (EM2) level in the central nervous system after continuous morphine exposure was observed, which suggested that increase of EM2 could be an alternative novel method for opioid dependence. As a short peptide, the short half-life of EM2 limits its clinical usage through conventional administration. In the present study, we engineered an EM2 gene using a signal peptide of mouse growth factor for an out-secretory expression of EM2 and an adenovirus as a vector, which ultimately sustained the release of EM-2. After administration of the adenovirus in central nervous system, a sustained increase of EM2 level in the cerebral spinal fluid (CSF) was observed along with a reduction of morphine withdrawal syndrome. These findings suggest that the engineered EM2 gene delivered to the central nervous system could be a novel therapeutics for withdrawal syndrome in opioid dependent subjects. PMID- 27003294 TI - Association between Body Mass Index, Asymmetric Dimethylarginine and Risk of Cardiovascular Events and Mortality in Norwegian Patients with Suspected Stable Angina Pectoris. AB - BACKGROUND: Asymmetric dimethylarginine (ADMA) is associated with increased risk of atherosclerotic cardiovascular disease and mortality through inhibition of nitrogen oxide (NO) synthesis. As positive correlations between serum concentrations of NO and body mass index (BMI) have been observed, we aimed to explore whether the potential associations between plasma ADMA levels and the risk of acute myocardial infarction (AMI) and mortality were modified by BMI. METHODS: Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HR) for AMI, cardiovascular death and all-cause mortality according to baseline plasma ADMA levels in 4122 patients with suspected stable angina pectoris. Analyses were subsequently repeated in patients with BMI below (low BMI) or above (high BMI) median. RESULTS: A total of 2982 patients (72%) were men. Median (range) age, plasma ADMA level and BMI were 62 (21-88) years, 0.54 (0.10-1.25) MUmol/L and 26.3 (18.5-54.3) kg/m2, respectively. During a mean (standard deviation) follow-up time of 4.7 (1.4) years, 337 (8%) patients suffered from an AMI, 300 (7%) died, whereof 165 (55%) due to cardiovascular disease. Each 0.1 MUmol/L increment in plasma ADMA level was associated with an increased risk of AMI (HR (95% CI) 1.21 (1.08, 1.35) and cardiovascular death 1.30 (1.13, 1.49) in participants with low BMI only. Interactions were significant for AMI (p = 0.04) and CV death (p = 0.03). BMI did not modify the association between plasma ADMA levels and all-cause mortality. CONCLUSION: Plasma ADMA levels were associated with risk of AMI and cardiovascular death among patients with low BMI only. PMID- 27003295 TI - An early developmental vertebrate model for nanomaterial safety: bridging cell based and mammalian toxicity assessment. AB - AIM: With the rise in production of nanoparticles (NPs) for an ever-increasing number of applications, there is an urgent need to efficiently assess their potential toxicity. We propose a NP hazard assessment protocol that combines mammalian cytotoxicity data with embryonic vertebrate abnormality scoring to determine an overall toxicity index. RESULTS: We observed that, after exposure to a range of NPs, Xenopus phenotypic scoring showed a strong correlation with cell based in vitro assays. Magnetite-cored NPs, negative for toxicity in vitro and Xenopus, were further confirmed as nontoxic in mice. CONCLUSION: The results highlight the potential of Xenopus embryo analysis as a fast screening approach for toxicity assessment of NPs, which could be introduced for the routine testing of nanomaterials. PMID- 27003296 TI - Genetic Diversity and Population Structure of the Rare and Endangered Plant Species Pulsatilla patens (L.) Mill in East Central Europe. AB - Pulsatilla patens s.s. is a one of the most endangered plant species in Europe. The present range of this species in Europe is highly fragmented and the size of the populations has been dramatically reduced in the past 50 years. The rapid disappearance of P. patens localities in Europe has prompted the European Commission to initiate active protection of this critically endangered species. The aim of this study was to estimate the degree and distribution of genetic diversity within European populations of this endangered species. We screened 29 populations of P. patens using a set of six microsatellite primers. The results of our study indicate that the analyzed populations are characterized by low levels of genetic diversity (Ho = 0.005) and very high levels of inbreeding (FIS = 0.90). These results suggest that genetic erosion could be partially responsible for the lower fitness in smaller populations of this species. Private allelic richness was very low, being as low as 0.00 for most populations. Average genetic diversity over loci and mean number of alleles in P. patens populations were significantly correlated with population size, suggesting severe genetic drift. The results of AMOVA point to higher levels of variation within populations than between populations.The results of Structure and PCoA analyses suggest that the genetic structure of the studied P. patens populations fall into three clusters corresponding to geographical regions. The most isolated populations (mostly from Romania) formed a separate group with a homogeneous gene pool located at the southern, steppic part of the distribution range. Baltic, mostly Polish, populations fall into two genetic groups which were not fully compatible with their geographic distribution.Our results indicate the serious genetic depauperation of P. patens in the western part of its range, even hinting at an ongoing extinction vortex. Therefore, special conservation attention is required to maintain the populations of this highly endangered species of European Community interest. PMID- 27003297 TI - Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome. AB - Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID- 27003298 TI - Oxidative Stress and DNA Damage in Untreated First-Episode Psychosis in Adolescents. AB - OBJECTIVE: Oxidative stress has been reported to play a role in the psychopathology of schizophrenia, though only a few studies have investigated the relationship between early-onset schizophrenia and oxidative stress. The aim of the present study is to evaluate the level of oxidative stress and the presence of DNA damage in first-episode psychosis (FEP) in adolescents. METHODS: This study was conducted in the Department of Child Psychiatry of the Dicle University Hospital. It included 20 adolescent patients (age 11-17 years) with psychosis (acute psychosis, schizophreniform disorder, or schizophrenia) according to DSM IV criteria who had received no previous psychiatric therapy (patient group) and 20 age/gender-matched healthy adolescents (control group). Structured psychiatric interviews [Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL) and Positive and Negative Symptom Scale (PANSS)] were conducted on the patients, and the Clinical Global Impressions (CGI) scale was used to evaluate the severity of disease. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-hydroxy-2-deoxyguanosine (8 OHdG) levels were determined using the ELISA method and commercial ELISA kits. RESULTS: The mean age was 14.5 +/- 1.6 years in the FEP group (male-to-female ratio: 8/12) and 14.4 +/- 1.5 years in the control group (male-to-female ratio: 8/12). There were no differences between the patient and control groups in terms of SOD, GPx, or 8-OHdG values (p > 0.05). CONCLUSIONS: This study on DNA damage and oxidative stress in FEP in adolescents had a small sample size, and our data suggest that oxidative stress is associated with a chronic disease course rather than being an early sign of early-onset schizophrenia. PMID- 27003299 TI - Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals in the European Union. AB - CONTEXT: A growing body of evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to female reproductive disorders. OBJECTIVE: To calculate the associated combined health care and economic costs attributable to specific EDC exposures within the European Union (EU). DESIGN: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. Cost-of-illness estimation used multiple peer-reviewed sources. SETTING, PATIENTS AND PARTICIPANTS AND INTERVENTION: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. RESULTS: The most robust EDC-related data for female reproductive disorders exist for 1) diphenyldichloroethene attributable fibroids and 2) phthalate-attributable endometriosis in Europe. In both cases, the strength of epidemiological evidence was rated as low and the toxicological evidence as moderate, with an assigned probability of causation of 20%-39%. Across the EU, attributable cases were estimated to be 56 700 and 145 000 women, respectively, with total combined economic and health care costs potentially reaching ?163 million and ?1.25 billion. CONCLUSIONS: EDCs (diphenyldichloroethene and phthalates) may contribute substantially to the most common reproductive disorders in women, endometriosis and fibroids, costing nearly ?1.5 billion annually. These estimates represent only EDCs for which there were sufficient epidemiologic studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs. PMID- 27003300 TI - Fibroblast Growth Factor-23 (FGF-23) Levels Differ Across Populations by Degree of Industrialization. AB - CONTEXT: Compensatory increases in fibroblast growth factor 23 (FGF23) with increasing phosphate intake may adversely impact health. However, population and clinical studies examining the link between phosphate intake and FGF23 levels have focused mainly on populations living in highly industrialized societies in which phosphate exposure may be homogenous. OBJECTIVE: The objective of the study was to contrast dietary phosphate intake, urinary measures of phosphate excretion, and FGF23 levels across populations that differ by the level of industrialization. DESIGN: This was a cross-sectional analysis of three populations. SETTING: The study was conducted in Maywood, Illinois; Mahe Island, Seychelles; and Kumasi, Ghana. PARTICIPANTS: Adults with African ancestry aged 25 45 years participated in the study. MAIN OUTCOME: FGF23 levels were measured. RESULTS: The mean age was 35.1 (6.3) years and 47.9% were male. Mean phosphate intake and fractional excretion of phosphate were significantly higher in the United States vs Ghana, whereas no significant difference in phosphate intake or fractional excretion of phosphate was noted between the United States and Seychelles for men or women. Overall, median FGF23 values were 57.41 RU/mL (interquartile range [IQR] 43.42, 75.09) in the United States, 42.49 RU/mL (IQR 33.06, 55.39) in Seychelles, and 33.32 RU/mL (IQR 24.83, 47.36) in Ghana. In the pooled sample, FGF23 levels were significantly and positively correlated with dietary phosphate intake (r = 0.11; P < .001) and the fractional excretion of phosphate (r = 0.13; P < .001) but not with plasma phosphate levels (r = -0.001; P = .8). Dietary phosphate intake was significantly and positively associated with the fractional excretion of phosphate (r = 0.23; P < .001). CONCLUSION: The distribution of FGF23 levels in a given population may be influenced by the level of industrialization, likely due to differences in access to foods preserved with phosphate additives. PMID- 27003301 TI - Acute Female Hypogonadism Alters Adipose Tissue Fatty Acid Storage Factors and Chylomicronemia. AB - CONTEXT: Chronic sex steroid deficiency has effects on adipose fatty acid (FA) storage mechanisms and fat oxidation, but the chronology of events are not well understood. OBJECTIVE: The objective of the study was to examine the acute effects of female sex steroid suppression on cellular mechanisms affecting abdominal and femoral subcutaneous adipose tissue FA storage. DESIGN: This study had a randomized, longitudinal, parallel study design. SETTING: The study was conducted at the Mayo Clinic Clinical Research Unit. PARTICIPANTS: Thirty-eight nonsmoking premenopausal women aged 18-50 years participated in the study. INTERVENTION: The intervention included randomization to receive one of the following: 1) no treatment (control), 2) 3.75 mg of Lupron, or 3) 3.75 mg of Lupron and estrogen, but not progesterone, replacement for 49 days, resulting in at least 4 weeks of sex steroid suppression. MAIN OUTCOME MEASURES: Body composition, fat cell size, postprandial chylomicron and nonchylomicron triglyceride concentrations, adipose tissue meal FA storage, direct free fatty acid storage, lipoprotein lipase, acyl CoA synthetase, and diacylglycerol acyltransferase activities, and CD36 content were measured. RESULTS: Compared with the control group, the fed state femoral lipoprotein lipase activity was reduced in women taking Lupron and those taking Lupron and estrogen replacement. In addition, we observed significantly greater postprandial chylomicronemia in the Lupron group than in the other two groups. There were no differences in overall fat storage and oxidation. Depending on the mode of data expression (per unit lipid vs per 1000 adipocytes), there were modest changes in acyl CoA synthetase, diacylglycerol acyltransferase, and CD36 in response to acute sex hormone suppression. CONCLUSIONS: Our results suggest estrogen and progesterone may have different effects on the regulation of FA metabolism and that acute sex steroid deficiency in women does not alter fat storage and oxidation. PMID- 27003303 TI - Metabolic and Transcriptional Changes in Cultured Muscle Stem Cells from Low Birth Weight Subjects. AB - CONTEXT/OBJECTIVE: Developmental programming of human muscle stem cells could in part explain why individuals born with low birth weight (LBW) have an increased risk of developing type 2 diabetes (T2D) later in life. We hypothesized that immature muscle stem cell functions including abnormal differentiation potential and metabolic function could link LBW with the risk of developing T2D. Design/Settings/Participants: We recruited 23 young men with LBW and 16 age matched control subjects with normal birth weight. Biopsies were obtained from vastus lateralis, and muscle stem cells were isolated and cultured into fully differentiated myotubes. MAIN OUTCOME MEASURES: We studied glucose uptake, glucose transporters, insulin signaling, key transcriptional markers of myotube maturity, selected site-specific DNA methylation, and mitochondrial gene expression. RESULTS: We found reduced glucose uptake as well as decreased levels of glucose transporter-1 and -4 mRNA and of the Akt substrate of 160-kDa mRNA and protein in myotubes from LBW individuals compared with normal birth weight individuals. The myogenic differentiation markers, myogenin and myosin heavy chain 1 and 2, were decreased during late differentiation in LBW myotubes. Additionally, mRNA levels of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha and cytochrome c oxidase polypeptide 7A were reduced in LBW myotubes. Decreased gene expression was not explained by changes in DNA methylation levels. CONCLUSION: We demonstrate transcriptional and metabolic alterations in cultured primary satellite cells isolated from LBW individuals after several cell divisions, pointing toward a retained intrinsic defect conserved in these myotubes. PMID- 27003302 TI - Steroid Sulfatase Deficiency and Androgen Activation Before and After Puberty. AB - CONTEXT: Steroid sulfatase (STS) cleaves the sulfate moiety off steroid sulfates, including dehydroepiandrosterone (DHEA) sulfate (DHEAS), the inactive sulfate ester of the adrenal androgen precursor DHEA. Deficient DHEA sulfation, the opposite enzymatic reaction to that catalyzed by STS, results in androgen excess by increased conversion of DHEA to active androgens. STS deficiency (STSD) due to deletions or inactivating mutations in the X-linked STS gene manifests with ichthyosis, but androgen synthesis and metabolism in STSD have not been studied in detail yet. PATIENTS AND METHODS: We carried out a cross-sectional study in 30 males with STSD (age 6-27 y; 13 prepubertal, 5 peripubertal, and 12 postpubertal) and 38 age-, sex-, and Tanner stage-matched healthy controls. Serum and 24-hour urine steroid metabolome analysis was performed by mass spectrometry and genetic analysis of the STS gene by multiplex ligation-dependent probe amplification and Sanger sequencing. RESULTS: Genetic analysis showed STS mutations in all patients, comprising 27 complete gene deletions, 1 intragenic deletion and 2 missense mutations. STSD patients had apparently normal pubertal development. Serum and 24-hour urinary DHEAS were increased in STSD, whereas serum DHEA and testosterone were decreased. However, total 24-hour urinary androgen excretion was similar to controls, with evidence of increased 5alpha-reductase activity in STSD. Prepubertal healthy controls showed a marked increase in the serum DHEA to DHEAS ratio that was absent in postpubertal controls and in STSD patients of any pubertal stage. CONCLUSIONS: In STSD patients, an increased 5alpha-reductase activity appears to compensate for a reduced rate of androgen generation by enhancing peripheral androgen activation in affected patients. In healthy controls, we discovered a prepubertal surge in the serum DHEA to DHEAS ratio that was absent in STSD, indicative of physiologically up-regulated STS activity before puberty. This may represent a fine tuning mechanism for tissue-specific androgen activation preparing for the major changes in androgen production during puberty. PMID- 27003304 TI - Exposure to Famine in Early Life and Nonalcoholic Fatty Liver Disease in Adulthood. AB - CONTEXT: Epidemiologic studies have indicated that early life nutrition influences later risk of obesity, type 2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is also considered a metabolic disease. OBJECTIVE: The aim was to explore the association between adult NAFLD and fetal or childhood exposure to Great Chinese Famine between 1959 and 1962 during fetal and childhood period. DESIGN AND SETTING: In total, 5306 subjects from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study were divided into a fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and nonexposed (1963-1974, reference) group. MAIN OUTCOME MEASURE: The degrees of steatosis of NAFLD were determined by ultrasonography. RESULTS: The prevalences of NAFLD in the nonexposed (1963-1974), fetal-exposed, and childhood-exposed participants were 55.9%, 55.8%, and 55.4% in men and 33.0%, 46.3%, and 51.7% in women, respectively. Compared with those nonexposed, fetal- and childhood-exposed women but not men had a significantly higher prevalence of moderate-severe steatosis (P < .05). A significant association existed in women between increased alanine aminotransferase and both fetal and childhood exposure to famine, after adjusting for age, rural/urban residence, economic status, body mass index, diabetes, dyslipidemia, and hypertension (both P < .05). Famine exposure during the fetal period (odds ratio 1.77, 95% confidence interval 1.22, 2.57) and childhood (odds ratio 1.82, 95% confidence interval 1.35, 2.46) was associated with an increased prevalence of moderate-severe NAFLD in women in the above fully adjusted model. CONCLUSIONS: Exposure to the Great Famine in early life had sex-specific association with moderate-severe NAFLD. This indicates that malnutrition in early life may influence the development of adult NAFLD; thus pregnant women and their infants and children may require the highest priority in obtaining nutritional relief. PMID- 27003305 TI - Cholecystokinin-Induced Gallbladder Emptying and Metformin Elicit Additive Glucagon-Like Peptide-1 Responses. AB - CONTEXT: Bile acids have been suggested to mediate glucagon-like peptide-1 (GLP 1) secretion. Metformin, too, has been shown to increase GLP-1 levels. The effect of gallbladder emptying, metformin, or a combination has, however, never been studied. OBJECTIVE: We hypothesized that cholecystokinin (CCK)-8-induced gallbladder emptying stimulates human GLP-1 secretion and that metformin would potentiate this effect. DESIGN: A double-blinded, randomized study. SETTING: The study was conducted at a specialized research unit. PARTICIPANTS: Ten healthy male subjects with no family history of diabetes (age, 22 [range, 20-32] years; body mass index, 21.7 [19.3-24.2] kg/m(2); fasting plasma glucose, 4.9 [4.7-5.3] mm; and glycosylated hemoglobin A1c, 5.1 [4.4-5.8] %). INTERVENTION: On 4 separate days, the subjects received metformin or placebo and a concomitant 60 minute intravenous infusion of saline or CCK. Blood was sampled for 4 hours, and gallbladder volume was measured by ultrasound. MAIN OUTCOME MEASURES: Plasma levels of GLP-1. RESULTS: CCK-induced gallbladder emptying and metformin alone (no observed effect on gallbladder emptying) both elicited significant and additive GLP-1 responses. Metformin alone or combined with gallbladder emptying elicited a significant peptide YY response. CCK-induced gallbladder emptying resulted in a short-lasting glucose-dependent insulinotropic polypeptide response independent of metformin. No effects were seen on plasma glucose, insulin, C peptide, or gastrin. CONCLUSIONS: CCK-induced gallbladder emptying in healthy subjects elicits significant GLP-1 secretion, which can be potentiated by metformin. PMID- 27003306 TI - Deletion of CPEB1 Gene: A Rare but Recurrent Cause of Premature Ovarian Insufficiency. AB - CONTEXT: Premature ovarian insufficiency (POI) may be secondary to chemotherapy, radiotherapy, or environmental factors. Genetic causes are identified in 20-25% of cases, but most POI cases remain idiopathic. OBJECTIVE: This study aimed to identify new genes involved in POI and to characterize the implication of CPEB1 gene in POI. DESIGN AND SETTING: This was a case report and cohort study replicate conducted in academic medical centers. PATIENTS AND METHODS: A deletion including CPEB1 gene was first identified in a patient with primary amenorrhea. Secondly, 191 sporadic POI cases and 68 familial POI cases were included. For each patient, karyotype was normal and FMR1 premutation was excluded. Search for CPEB1 deletions was performed by quantitative multiplex PCR of short fluorescent fragments or DNA microarray analysis. Gene sequencing of CPEB1 was performed for 95 patients. RESULTS: We identified three patients carrying a microdeletion in band 15q25.2. The proximal breakpoint, for the three patients, falls within a low copy repeat region disrupting the CPEB1 gene, which represents a strong candidate gene for POI as it is known to be implicated in oocyte meiosis. No mutation was identified by sequencing CPEB1 gene. Therefore, heterozygous deletion of CPEB1 gene leading to haploinsufficiency could be responsible for POI in humans. CONCLUSION: Microdeletions of CPEB1 were identified in 1.3% of patients with POI, whereas no mutation was identified. This microdeletion is rare but recurrent as it is mediated by nonallelic homologous recombination due to the existence of low copy repeats in the region. This result demonstrates the importance of DNA microarray analysis in etiological evaluation and counseling of patients with POI. PMID- 27003307 TI - Cumulus Cell Mitochondrial Resistance to Stress In Vitro Predicts Oocyte Development During Assisted Reproduction. AB - CONTEXT: Complex cumulus cell-oocyte interactions govern energy utilization during oocyte development. OBJECTIVE: This study investigates the relationship of cumulus cell mitochondria with oocyte development during ovarian stimulation for in vitro fertilization (IVF). DESIGN: This is a prospective cohort study. SETTING: The setting was an academic center. PATIENTS: Thirty women underwent ovarian stimulation for IVF. INTERVENTION(S): Pooled cumulus cells were collected; numbers of total and mature oocytes and two-pronuclear (day 1), six- to eight-cell cleavage (day 3), and blastocyst (day 5) embryos were recorded. MAIN OUTCOME MEASURE(S): A mitochondrial bioassay was developed with Jurkat cells and used with cumulus cells from IVF patients to correlate mitochondrial membrane potential resistance to carbonyl cyanide 3-chlorophenylhydrazone (CCCP) stress with oocyte development and embryogenesis. RESULTS: Adjusting for FSH administered and maternal age, cumulus cell mitochondrial membrane potential resistance to CCCP positively correlated with numbers of total (P < .025) and mature (P < .025) oocytes retrieved. The highest oocyte numbers that correlated with cumulus cell mitochondrial membrane potential occurred in women with the greatest ovarian response to FSH (mitochondrial membrane potential resistance to CCCP-log FSH interactions: total oocytes P < .025; mature oocytes P < .05). Multiple regression modeling of mature oocyte numbers, age, and cumulus cell mitochondrial membrane potential resistance to CCCP showed that numbers of mature oocytes best correlated with numbers of embryos at all stages (P < .0001). CONCLUSION: During ovarian stimulation for IVF, cumulus cell mitochondrial membrane potential resistance to stress correlates with numbers of total and mature oocytes retrieved, suggesting that cumulus cell-oocyte interactions involving energy facilitate oocyte development. PMID- 27003309 TI - Acyl hydrolases from trans-AT polyketide synthases target acetyl units on acyl carrier proteins. AB - Acyl hydrolase (AH) domains are a common feature of trans-AT PKSs. They have been hypothesised to perform a proofreading function by removing acyl chains from stalled sites. This study determines the substrate tolerance of the AH PedC for a range of acyl-ACPs. Clear preference towards short, linear acyl-ACPs is shown, with acetyl-ACP the best substrate. These results imply a more targeted housekeeping role for PedC: namely the removal of unwanted acetyl groups from ACP domains caused by erroneous transfer of acetyl-CoA, or possibly by decarboxylation of malonyl-ACP. PMID- 27003310 TI - Hybrid Molecular Imaging in Differentiated Thyroid Carcinoma. AB - Radioactive isotopes of radioiodine are frequently used in differentiated thyroid carcinoma (DTC) both for diagnosis and therapy. Their accumulation in thyroid cancer tissue is dependent on the expression and activity of the sodium-iodide symporter (NIS). Scintigraphic imaging using either planar or single-photon emission computed tomography (SPECT) cameras allows the visualization of their distribution within the human body. Due to only a poor visualization of morphology by these techniques, their diagnostic accuracy is, however, limited. This limitation is overcome when hybrid systems integrating a SPECT camera with an X-ray CT scanner are used. Roughly one third of patients with diagnostically unclear foci of radioiodine accumulation will benefit from the use of SPECT/CT, also in terms of therapeutic management. SPECT/CT has, therefore, become the gold standard of nuclear imaging in DTC. NIS expression may be absent in DTC. In this case, the glucose transporters are usually upregulated. Therefore, PET/CT using 18F-deoxyglucose can be used to diagnose and localize tumor recurrence as a prerequisite to, in particular, surgical intervention. PMID- 27003308 TI - Quantitative Three-Dimensional Imaging of Lipid, Protein, and Water Contents via X-Ray Phase-Contrast Tomography. AB - X-ray phase-contrast computed tomography is an emerging imaging technology with powerful capabilities for three-dimensional (3D) visualization of weakly absorbing objects such as biological soft tissues. This technique is an extension of existing X-ray applications because conventional attenuation-contrast images are simultaneously acquired. The complementary information provided by both the contrast modalities suggests that enhanced material characterization is possible when performing combined data analysis. In this study, we describe how protein, lipid, and water concentrations in each 3D voxel can be quantified by vector decomposition. Experimental results of dairy products, porcine fat and rind, and different human soft tissue types are presented. The results demonstrate the potential of phase-contrast imaging as a new analysis tool. The 3D representations of protein, lipid, and water contents open up new opportunities in the fields of biology, medicine, and food science. PMID- 27003311 TI - Categorical variables with many categories are preferentially selected in bootstrap-based model selection procedures for multivariable regression models. AB - Automated variable selection procedures, such as backward elimination, are commonly employed to perform model selection in the context of multivariable regression. The stability of such procedures can be investigated using a bootstrap-based approach. The idea is to apply the variable selection procedure on a large number of bootstrap samples successively and to examine the obtained models, for instance, in terms of the inclusion of specific predictor variables. In this paper, we aim to investigate a particular important problem affecting this method in the case of categorical predictor variables with different numbers of categories and to give recommendations on how to avoid it. For this purpose, we systematically assess the behavior of automated variable selection based on the likelihood ratio test using either bootstrap samples drawn with replacement or subsamples drawn without replacement from the original dataset. Our study consists of extensive simulations and a real data example from the NHANES study. Our main result is that if automated variable selection is conducted on bootstrap samples, variables with more categories are substantially favored over variables with fewer categories and over metric variables even if none of them have any effect. Importantly, variables with no effect and many categories may be (wrongly) preferred to variables with an effect but few categories. We suggest the use of subsamples instead of bootstrap samples to bypass these drawbacks. PMID- 27003312 TI - Surgical Management of Clostridium difficile Infection: The Role of Colectomy. AB - Management of Clostridium difficile infections is usually accomplished through appropriate antimicrobial therapy. However, in patients that do not respond to this therapy, rapid and potentially lethal progressive organ dysfunction care occurs. Although supportive care and continued antimicrobial therapy is important, surgical therapy is critical to eradication of the inflammatory process and reversal of the dysregulated immunity associated with severe C. difficile infections. In the following paper, the role of colectomy is reviewed. PMID- 27003313 TI - Biodegradable system for drug delivery of hydrolytically labile azanucleoside drugs. AB - BACKGROUND: The archetypal DNA methyltransferase inhibitors, 5-azacytidine (AZA) and 5-aza-2'-deoxycytidine (DAC) are potent antineoplastic agents used in the treatment of mainly, blood malignancies. However, the administration of these drugs is confounded by their hydrolytic lability which decreases plasma circulation time. Here, we describe a new biodegradable, polyanhydride formulation for drug delivery that circumvents this drawback. METHODS: Injectable/implantable polymeric microbeads containing dispersed microcrystals of hydrophilic AZA or DAC packed in a dry environment are protected from hydrolysis, until the hydrolytic zone reaches the core. Diclofenac is embedded into the formulation to decrease any local inflammation. The efficacy of the formulations was confirmed by monitoring the induced demethylation, and cytostatic/cytotoxic effects of continuous drug release from the time-course dissolution of the microbeads, using an in vitro developed cell based reporter system. RESULTS: Poly(sebaccic acid-co-1,4-cyclohexanedicarboxylic acid) containing 30 wt. % drug showed zero-order release (R(2) = 0.984 for linear regression), and release rate of 10.0 %/h within the first 5 h, and subsequent slower release of the remaining drug, thus maintaining the level of drugs in the outer environment considerably longer than the typical plasma half-life of free azanucleosides. At lower concentrations, the differences between powder drug formulations and microbeads were very low or negligible, however, at higher concentrations, we discovered equivalent or increasing effects of the drugs loaded in microbeads. CONCLUSIONS: The study provides evidence that microbead formulations of the hydrolytically labile azanucleoside drugs could prevent their chemical decomposition in aqueous solution, and effectively increase plasma circulation time. PMID- 27003314 TI - MicroRNAs in the key events of systemic lupus erythematosus pathogenesis. AB - BACKGROUND: Small non-coding RNA molecules (miRs) are involved in immune cell maturation and function and might influence immunopathological processes of systemic lupus erythematosus (SLE) pathogenesis. METHODS AND RESULTS: This paper presents the results of a literature search for publications dealing with the relationship between miRs and pathological factors related to SLE such as genetic background, immune dysregulation and gender-associated differences participating in SLE development. In SLE, distinct miRs are differentially expressed in SLE cells of innate and adaptive immunity. The miR-146a and miR-155 genes, among others, interfere with intracellular signalling pathways downstream of toll-like receptors 7 and 9 (TLR- 7, TLR-9) and influences interferon (IFN)-type I synthesis in plasmacytoid dendritic cells. In T and B cells, miR-126, miR-21, miR 146a, miR-155, miR-1246 and others might influence gene expression by epigenetic modifications, support abnormal cytosine release, differentiation of cell subsets, B cell hyperactivity and autoantibody production. Besides, estrogen might up- and downregulate immunologically active miRs, which are potential mediators of hormonal influences in SLE development. Moreover, SLE genetic basis included some polymorphisms of the miR-146a gene, which varies across populations. CONCLUSION: Distinct miRs are differentially expressed in both SLE mice models and human patients and promote autoimmune features of immune processes. MiRs are important molecules modulating susceptibility to SLE as well as its onset, clinical diversity and progression. PMID- 27003316 TI - 3- and 4-(alpha-diazobenzyl)pyridine-N-oxides as photoresponsive magnetic couplers for 2p-4f heterospin systems: formation of carbene-Tb(III) and carbene Dy(III) single-molecule magnets. AB - 3- and 4-(alpha-diazophenyl)pyridine-N-oxides, and , were prepared as new photoresponsive magnetic couplers in heterospin systems. Lanthanide dinuclear complexes, [Ln(III)(tta)3()]2; Ln(III) = Gd (), Tb (), and Dy () and tta = 4,4,4 trifluoro-1-(2-thienyl)-1,3-butanedionate, bridged with in MU2 coordination mode were obtained. The obtained , , and were isostructures. The isomeric complex, [Tb(III)(tta)3()]2 was also prepared. In the carbene-Ln(III) complexes [Ln(III)(tta)3( and )]2 generated by photolysis, regioselectively interacted with the Ln(III) ions through pyridine-N-oxide, in which the magnetic coupling of was weakly ferromagnetic, while that of was insignificant. Before and after irradiation of , no SMM behavior was observed. In contrast, the Tb(III) and Dy(III) complexes being anisotropic functioned as heterospin SMMs. Before irradiation, showed no SMM behavior. After irradiation, two species showing slow magnetic relaxations were produced and one of them exhibited SMM behavior with the thermal activation barrier, Ueff/kB = 30 K, and tau0 = 5.8 * 10(-8) s. In , SMM behaviors were observed before and after irradiation, and the Ueff/kB value of 102 K (tau0 = 3.6 * 10(-7) s) before irradiation was reduced to 39 K (tau0 = 1.5 * 10(-8) s) after irradiation. PMID- 27003315 TI - Epidemiology of hospital-acquired pneumonia: Results of a Central European multicenter, prospective, observational study compared with data from the European region. AB - BACKGROUND: Hospital-acquired pneumonia (HAP) is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of HAP. This project was aimed at collecting multicenter epidemiological data on patients with HAP in the Czech Republic and comparing them with supraregional data. METHODS: This prospective, multicenter, observational study processed data from a database supported by a Czech Ministry of Health grant project. Included were all consecutive patients aged 18 and over who were admitted to participating intensive care units (ICUs) between 1 May 2013 and 31 December 2014 and met the inclusion criterion of having HAP. The primary endpoint was to analyze the relationships between 30-day mortality (during the stay in or after discharge from ICUs) and the microbiological etiological agent and adequacy of initial empirical antibiotic therapy in HAP patients. RESULTS: The group dataset contained data on 330 enrolled patients. The final validated dataset involved 214 patients, 168 males (78.5%) and 46 females (21.5%), from whom 278 valid lower airway samples were obtained. The mean patient age was 59.9 years. The mean APACHE II score at admission was 21. Community-acquired pneumonia was identified in 13 patients and HAP in 201 patients, of whom 26 (12.1%) had early-onset and 175 (81.8%) had late-onset HAP. Twenty-two bacterial species were identified as etiologic agents but only six of them exceeded a frequency of detection of 5% (Klebsiella pneumoniae 20.4%, Pseudomonas aeruginosa 20.0%, Escherichia coli 10.8%, Enterobacter spp. 8.1%, Staphylococcus aureus 6.2% and Burkholderia cepacia complex 5.8%). Patients infected with Staphylococcus aureus had significantly higher rates of early-onset HAP than those with other etiologic agents. The overall 30-day mortality rate for HAP was 29.9%, with 19.2% mortality for early-onset HAP and 31.4% mortality for late-onset HAP. Patients with late onset HAP receiving adequate initial empirical antibiotic therapy had statistically significantly lower 30-day mortality than those receiving inadequate initial antibiotic therapy (23.8% vs 42.9%). Patients with ventilator associated pneumonia (VAP) had significantly higher mortality than those who developed HAP with no association with mechanical ventilation (34.6% vs 12.7%). Patients having VAP treated with adequate initial antibiotic therapy had lower 30 day mortality than those receiving inadequate therapy (27.2% vs 44.8%). CONCLUSIONS: The present study was the first to collect multicenter data on the epidemiology of HAP in the Central European Region, with respect to the incidence of etiologic agents causing HAP. It was concerned with relationships between 30 day patient mortality and the type of HAP, etiologic agent and adequacy of initial empirical antibiotic therapy. PMID- 27003319 TI - Development of pediatric orthopedic training and practice in China: administrative, socioeconomic, and cultural impacts. PMID- 27003318 TI - Poly(ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Benzo(a)pyrene Induced Cell Transformation. AB - Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant and known carcinogen, which can induce malignant transformation in rodent and human cells. Poly(ADP-ribose) glycohydrolase (PARG), the primary enzyme that catalyzes the degradation of poly(ADP-ribose) (PAR), has been known to play an important role in regulating DNA damage repair and maintaining genomic stability. Although PARG has been shown to be a downstream effector of BaP, the role of PARG in BaP induced carcinogenesis remains unclear. In this study, we used the PARG-deficient human bronchial epithelial cell line (shPARG) as a model to examine how PARG contributed to the carcinogenesis induced by chronic BaP exposure under various concentrations (0, 10, 20 and 40 MUM). Our results showed that PARG silencing dramatically reduced DNA damages, chromosome abnormalities, and micronuclei formations in the PARG-deficient human bronchial epithelial cells compared to the control cells (16HBE cells). Meanwhile, the wound healing assay showed that PARG silencing significantly inhibited BaP-induced cell migration. Furthermore, silencing of PARG significantly reduced the volume and weight of tumors in Balb/c nude mice injected with BaP induced transformed human bronchial epithelial cells. This was the first study that reported evidences to support an oncogenic role of PARG in BaP induced carcinogenesis, which provided a new perspective for our understanding in BaP exposure induced cancer. PMID- 27003320 TI - Phase evolution in sonochemically synthesized Fe(3+) doped BaTiO3 nanocrystallites: structural, magnetic and ferroelectric characterisation. AB - The properties of nanomaterials are highly dependent on their size, morphology, crystal phase, etc., which in turn depend on the method of synthesis. We report here the electrical and magnetic characterisation of sonochemically synthesized Fe(3+) doped nano BaTiO3 samples. The dopant ion concentration has been optimized and the coexistence of ferromagnetism and ferroelectricity has been observed in the sample. With increase in Fe(3+) doping from 0 to 20 mol%, a gradual phase change from tetragonal to hexagonal occurred in these sonochemically synthesized BaTiO3 nanomaterials. Below 15 mol% Fe concentration the material displays ferroelectric behaviour with the absence of any magnetic ordering, while at an Fe concentration of ~15 mol% the material exhibits both room temperature ferromagnetism and ferroelectricity. Ferromagnetism as well as relaxor type behaviour has been observed in the BaTiO3:Fe(3+)(20%) sample. We have studied the ferromagnetic and ferroelectric ordering in these sonochemically synthesized Fe(3+) doped BaTiO3 nanomaterials and have tried to correlate the results with their crystal structure and morphology. The origin of ferromagnetism in these materials has been attributed to both intrinsic as well as extrinsic factors. PMID- 27003321 TI - Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable. AB - There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng.kg.min with subsequent up-titration by 1 ng.kg.min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng.kg.min with an interquartile range (IQR) of 20-23 ng.kg.min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng.kg.min (range: 17 30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng.kg.min (IQR: 20-23.5), and the median up titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable. PMID- 27003322 TI - [Requirements for drug approval and additional benefits assessment: Regulatory aspects and experiences]. AB - The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G-BA and applicants. Under these aspects the BfArM and G-BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits. PMID- 27003323 TI - Adalimumab for Ocular Inflammation. AB - PURPOSE: To evaluate adalimumab as an immunomodulatory treatment for non infectious ocular inflammatory diseases. METHODS: Characteristics of patients treated with adalimumab were abstracted in a standardized chart review. Main outcomes measured were control of inflammation, corticosteroid-sparing effect, and visual acuity. RESULTS: In total, 32 patients with ocular inflammation were treated with adalimumab. The most common ophthalmic diagnoses were anterior uveitis, occurring in 15 patients (47%), and scleritis, occurring in 9 patients (28%). At 6 months of therapy, among 15 eyes with active inflammation, 7 (47%) became completely inactive, and oral prednisone was reduced to <=10 mg/day in 2 of 4 patients (50%). On average, visual acuity decreased by 0.13 lines during the first 6 months of treatment. Adalimumab was discontinued because of lack of effectiveness in four patients within 6 months. CONCLUSIONS: Adalimumab was moderately effective in controlling inflammation in a group of highly pre-treated cases of ocular inflammatory disease. PMID- 27003324 TI - Structural plasticity of the Salmonella FliS flagellar export chaperone. AB - The Salmonella FliS flagellar export chaperone is a highly alpha-helical protein. Proteolytic experiments suggest that FliS has a compact core. However, the calorimetric melting profile of FliS does not show any melting transition in the 25-110 degrees C temperature range. Circular dichroism measurements reveal that FliS is losing its helical structure over a broad temperature range upon heating. These observations indicate that FliS unfolds in a noncooperative way and its native state shows features reminiscent of the molten globule state of proteins possessing substantial structural plasticity. As FliS has several binding partners within the cell, conformational adaptability seems to be an essential requirement to fulfill its multiple roles. PMID- 27003325 TI - Loss of the calcium channel beta4 subunit impairs parallel fibre volley and Purkinje cell firing in cerebellum of adult ataxic mice. AB - The auxiliary voltage-gated calcium channel subunit beta4 supports targeting of calcium channels to the cell membrane, modulates ionic currents and promotes synaptic release in the central nervous system. beta4 is abundant in cerebellum and its loss causes ataxia. However, the type of calcium channels and cerebellar functions affected by the loss of beta4 are currently unknown. We therefore studied the structure and function of Purkinje cells in acute cerebellar slices of the beta4 (-/-) ataxic (lethargic) mouse, finding that loss of beta4 affected Purkinje cell input, morphology and pacemaker activity. In adult lethargic cerebellum evoked postsynaptic currents from parallel fibres were depressed, while paired-pulse facilitation and spontaneous synaptic currents were unaffected. Because climbing fibre input was spared, the parallel fibre/climbing fibre input ratio was reduced. The dendritic arbor of adult lethargic Purkinje cells displayed fewer and shorter dendrites, but a normal spine density. Accordingly, the width of the molecular and granular layers was reduced. These defects recapitulate the impaired cerebellar maturation observed upon Cav 2.1 ataxic mutations. However, unlike Cav 2.1 mutations, lethargic Purkinje cells also displayed a striking decrease in pacemaker firing frequency, without loss of firing regularity. All these deficiencies appear in late development, indicating the importance of beta4 for the normal differentiation and function of mature Purkinje cells networks. The observed reduction of the parallel fibre input, the altered parallel fibre/climbing fibre ratio and the reduced Purkinje cell output can contribute to the severe motor impairment caused by the loss of the calcium channel beta4 subunit in lethargic mice. PMID- 27003326 TI - Academic Productivity of Interventional Pulmonology Training Programs. AB - RATIONALE: The Hirsch index (h-index) has been validated as a measure of academic productivity and may be an appropriate tool to assess the scholarly activity of interventional pulmonology (IP). OBJECTIVES: This study aimed to elucidate the factors associated with increasing h-index scores among IP training programs. METHODS: A cross-sectional study was conducted of IP training programs across the United States and Canada. Data, including their respective h-index, number of publications, academic rank, geographic location, and possession of an advanced degree, were collected on IP faculty and fellows from 23 teaching institutions. MEASUREMENTS AND MAIN RESULTS: Ninety-three IP physicians (48 faculty, 45 fellows) in all were included in the study from 23 institutions with a total of 101 data points. The faculty h-index mean was 3.88. The proportion of faculty with an h-index greater than the mean value was increased significantly with higher academic rank (P < 0.0001). In addition, physicians holding an advanced degree beyond an M.D./D.O. had a significantly higher h-index than did those without (P = 0.0062). CONCLUSIONS: For academic interventional pulmonologists, the h-index rises with increasing academic rank and possession of an advanced degree. The h-index for IP is roughly comparable to that for other surgical and procedural-based specialties. PMID- 27003328 TI - Tuning the Activation Wavelength of Photochromic Oxazines. AB - The activation wavelength of a photochromic oxazine can be shifted bathochromically with the introduction of a methoxy substituent on the chromophore responsible for initiating the photochemical transformation. This structural modification permits switching under mild illumination conditions, enhances the photoisomerization quantum yield and ensures outstanding fatigue resistance. Thus, these results can guide the design of new members of this family of photoresponsive molecular switches with improved photochemical and photophysical properties. PMID- 27003327 TI - Triptolide mitigates radiation-induced pulmonary fibrosis via inhibition of axis of alveolar macrophages-NOXes-ROS-myofibroblasts. AB - PURPOSE: IR-induced pulmonary fibrosis is one of the most severe late complications of radiotherapy for lung cancer. It is urgently needed to discover a new drug for anti-IR lung fibrosis. Our previous studies have indicated that TPL exhibits both anti-IR lung fibrosis and anti-tumor activities. To reveal the mechanism of TPL on anti-IR lung fibrosis, alveolar macrophages (AMs) were examined for TPL effect on their axis of Nicotinamide adenine dinucleotide phosphate oxidase-reactive oxygen species (NOXes-ROS) and myofibroblast activation. METHODS AND MATERIALS: The fibrosis-prone C57BL/6 mice were irradiated with 15 Gy on whole chest, then one day later, mice were treated without or with TPL (i.v. 0.25 mg/kg, qod for 1 month). The AMs were collected from bronchoalveolar lavage fluids and studied for the production of ROS and the levels of NOXes. The effect of AMs on myofibroblast activation as labeled with F4/80 or alpha-SMA (alpha-smooth muscle actin) were examined using flow cytometry, Western blotting, or immunohistochemical staining. RESULTS: TPL effectively reduced the IR-induced lung fibrosis as evidenced by the less myofibroblasts, less collagen deposit and less ROS in the IR-lung tissues. We found that ROS which responsible for myofibroblasts activation was mainly from AMs and was NOX2 and NOX4 dependent. TPL significantly reduced the infiltrated AMs in IR-lung tissues, and in addition, down regulated the level of NOX2 and NOX4 in AMs both in vitro and in vivo. Furthermore, by inhibiting NOXes dependent ROS in AMs, TPL deprived AMs' paracrine activation of myofibroblasts. CONCLUSIONS: Our work demonstrated that the anti-fibrotic effect of TPL on IR induced pulmonary fibrosis was related to its inhibition on the axis of alveolar macrophages-NOXes-ROS-myofibroblasts. PMID- 27003329 TI - Severe Thrombocytopenia as Initial Signs of Primary Sjogren Syndrome in a 9-Year Old Female. PMID- 27003330 TI - Tacrolimus Concentration/Dose Ratio is Associated with Renal Function After Liver Transplantation. AB - BACKGROUND: The calcineurin inhibitor (CNI) tacrolimus (Tac) is an effective immunosuppressant used after liver transplantation (LTx), but is often associated with CNI nephrotoxicity. Currently, there is no simple clinical predictor for CNI nephrotoxicity after LTx. We hypothesized that the Tac metabolism rate - defined as the blood concentration normalized by its daily dose (the C/D ratio) - is associated with post-LTx renal impairment. MATERIAL AND METHODS: We analyzed the relationship between the C/D ratio and post-transplant renal function in 179 patients who underwent LTx between 2000 and 2012 and were initially immunosuppressed with Tac, mycophenolate mofetil, and prednisolone. Six months after LTx, 115 patients were categorized into 1 of 2 groups based on their Tac C/D ratio (<1.09 or >=1.09): fast (n=58) or slow (n=57) metabolizers. The renal function was determined 36 months after LTx using the estimated glomerular filtration rate (eGFR) as described by Cockcroft and Gault. RESULTS: At the time of LTx there was no statistically significant difference between the eGFR of fast and slow metabolizers. Six months (P=0.016), 12 months (P=0.001), and 36 months (P=0.018) after LTx, fast Tac metabolizers had significantly more impaired renal function than slow metabolizers. Because of a presumption of CNI nephrotoxicity, 32.8% of fast metabolizers and 14.0% of slow metabolizers were switched from Tac to other immunosuppressants (P=0.027). CONCLUSIONS: In this study, the Tac metabolism rate appears to influence renal function after LTx, suggesting that a C/D ratio of <1.09 is associated with increased CNI nephrotoxicity in LTx recipients. PMID- 27003331 TI - Correction to Investigation of (E)-3-[4-(2-Oxo-3-aryl-chromen-4 yl)oxyphenyl]acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators. PMID- 27003333 TI - Chemoselective Polymerizations from Mixtures of Epoxide, Lactone, Anhydride, and Carbon Dioxide. AB - Controlling polymer composition starting from mixtures of monomers is an important, but rarely achieved, target. Here a single switchable catalyst for both ring-opening polymerization (ROP) of lactones and ring-opening copolymerization (ROCOP) of epoxides, anhydrides, and CO2 is investigated, using both experimental and theoretical methods. Different combinations of four model monomers-epsilon-caprolactone, cyclohexene oxide, phthalic anhydride, and carbon dioxide-are investigated using a single dizinc catalyst. The catalyst switches between the distinct polymerization cycles and shows high monomer selectivity, resulting in block sequence control and predictable compositions (esters and carbonates) in the polymer chain. The understanding gained of the orthogonal reactivity of monomers, specifically controlled by the nature of the metal-chain end group, opens the way to engineer polymer block sequences. PMID- 27003332 TI - Unfavorable surgical outcomes in partial epilepsy with secondary bilateral synchrony: Intracranial electroencephalography study. AB - OBJECTIVE: Secondary bilateral synchrony (SBS) indicates bilaterally synchronous epileptiform discharges arising from a focal cortical origin. The present study aims to investigate SBS in partial epilepsy with regard to surgical outcomes and intracranial EEG findings. METHODS: We retrospectively reviewed consecutive patients who underwent epilepsy surgery following extraoperative intracranial electroencephalography (EEG) study from 2008 to 2012. The presence of SBS was determined based upon the results of scalp EEG monitoring performed for presurgical evaluations. We reviewed scalp EEG, neuroimaging, intracranial EEG findings, and surgical outcomes in patients with SBS. RESULTS: We found 12 patients with SBS who were surgically treated for intractable partial epilepsy. Nine (75%) patients had lateralized ictal semiology and only two (16.6%) patients showed localized ictal onset in scalp EEG. Brain MRI showed epileptogenic lesion in three (25%) patients. Intracranial EEG demonstrated that ictal onset zone was widespread or non-localized in six (50%) patients. Low-voltage fast activity was the most common ictal onset EEG pattern. Rapid propagation of ictal onset was noted in 10 (83.3%) patients. Eleven patients underwent resective epilepsy surgery and only two patients (18.2%) achieved seizure-freedom (median follow-up 56 months). MRI-visible brain lesions were associated with favorable outcomes (p=0.024). Patients with SBS, compared to frontal lobe epilepsy without SBS, showed lesser localization in ictal onset EEG (p=0.029) and more rapid propagation during evolution of ictal rhythm (p=0.015). CONCLUSIONS: The present results suggested that resective surgery for partial epilepsy with SBS should be decided carefully, especially in case of nonlesional epilepsy. Poor localization and rapid spread of ictal onset were prominent in intracranial EEG, which might contribute to incomplete resection of the epileptogenic zone and poor surgical outcomes. PMID- 27003334 TI - Metal-Free sp(2)-C-H Borylation as a Common Reactivity Pattern of Frustrated 2 Aminophenylboranes. AB - C-H borylation is a powerful and atom-efficient method for converting affordable and abundant chemicals into versatile organic reagents used in the production of fine chemicals and functional materials. Herein we report a facile C-H borylation of aromatic and olefinic C-H bonds with 2-aminophenylboranes. Computational and experimental studies reveal that the metal-free C-H insertion proceeds via a frustrated Lewis pair mechanism involving heterolytic splitting of the C-H bond by cooperative action of the amine and boryl groups. The adapted geometry of the reactive B and N centers results in an unprecedentently low kinetic barrier for both insertion into the sp(2)-C-H bond and intramolecular protonation of the sp(2)-C-B bond in 2-ammoniophenyl(aryl)- or -(alkenyl)borates. This common reactivity pattern serves as a platform for various catalytic reactions such as C H borylation and hydrogenation of alkynes. In particular, we demonstrate that simple 2-aminopyridinium salts efficiently catalyze the C-H borylation of hetarenes with catecholborane. This reaction is presumably mediated by a borenium species isoelectronic to 2-aminophenylboranes. PMID- 27003335 TI - Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells. AB - AIM: To investigate the effect of simvastatin on lipopolysaccharide (LPS) stimulated inflammatory cytokines, cell adhesion molecules and nuclear factor kappaB (NF-kappaB) transcription factors in human dental pulp cells (HDPCs). METHODOLOGY: The effect of LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using a 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) assay. The expression of inflammatory cytokines and cell adhesion molecules was evaluated by reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. NF-kappaB transcription factors were evaluated by Western blot analysis. Statistical analysis was performed with analysis of variance (anova). RESULTS: The viability of cells exposed to different concentrations of E. coli LPS, P. gingivalis LPS and simvastatin was not significantly different compared with that of control cells (P > 0.05). LPS significantly increased interleukin (IL)-1beta (P < 0.05) and IL-6 mRNA expression (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) (P < 0.05) and intercellular adhesion molecule-1 (ICAM-1) protein expression (P < 0.05) in HDPCs. Treatment with simvastatin significantly attenuated LPS-stimulated production of IL-1beta, IL-6, VCAM-1 and ICAM-1 (P < 0.05). Treatment with simvastatin decreased LPS-induced expression of p65 and phosphorylation of IkappaB and also significantly decreased the phosphorylation of p65 and IkappaB in the cytoplasm and the level of p65 in the nucleus (P < 0.05). CONCLUSIONS: Simvastatin has a suppressing effect on LPS induced inflammatory cytokine, cell adhesion molecules and NF-kappaB transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp-capping agent in vital pulp therapy. PMID- 27003336 TI - Historical context and the roots of Jenner's discovery. AB - May 2016 marks the 220th anniversary of Edward Jenner's first experimental vaccination using cowpox to protect against smallpox. Jenner's discovery, and its rapid adoption around the world, launched a medical revolution that continues to shape how we approach disease prevention. The historical roots of vaccination are found in the popularization of smallpox inoculation during the 18th century, part of an Enlightenment culture that fostered scientific inquiry and the global circulation of knowledge. Jenner was part of that culture and his study of cowpox stemmed from his varied interests as a natural historian, his contacts with leading savants in London, and his medical practice in a flourishing dairy area of England. The amazingly quick spread of vaccination resulted from organized hospital trials in major cities, the severe smallpox epidemic at the turn of the century, disease environment, and policies of European colonial powers. PMID- 27003337 TI - Association of rs4331426 and rs2057178 with Risk of Tuberculosis: Evidence from a Meta-Analysis. AB - AIMS: A growing number of genome-wide association studies (GWAS) have revealed associations between single-nucleotide polymorphisms (SNPs) and susceptibility to tuberculosis (TB). However, the results of these studies have been inconclusive. This study evaluated whether the SNPs rs4331426 and rs2057178, identified by GWAS, are associated with TB susceptibility. METHODS: We performed meta-analyses for rs4331426, based on eight case-control studies which included a total of 4988 TB cases and 9041 controls; and rs2057178, based on five case-control studies, including a total of 9400 TB cases and 14,459 controls. RESULTS: Our meta analyses indicated that both rs4331426 and rs2057178 were associated with increased risk of TB (G vs. A: odds ratio [OR] = 1.15, 95% confidence interval [CI]: 1.08-1.22 and A vs. G: OR = 0.84, 95% CI: 0.80-0.88, respectively), especially in an African subgroup. However, no significant TB association was found with rs4331426 in an Asian subgroup. CONCLUSIONS: These meta-analyses indicate that rs4331426 and rs2057178 might play a role in the risk of developing TB, especially in Africans; however, rs4331426 might not play a significant role in the risk of developing TB in Asians. PMID- 27003338 TI - Predicting the Efficiency of Photoswitches Using Force Analysis. AB - Photoswitches convert light into mechanical energy by exerting forces on their environment during photoisomerization. However, the mechanical efficiency of this conversion is limited because a plethora of internal modes of the photoswitch do not contribute to the desired switching function but are also changed during the photoisomerization. Here we present a computational approach to quantify the efficiency of a photoswitch during the initial motion on the excited-state potential energy surface. We demonstrate the gist of our method by looking at the excited-state relaxation of carbon monoxide. Subsequently, the photoswitching efficiency of p-coumaric acid is analyzed as one representative example of the approach. PMID- 27003340 TI - Mouse models reveal why Alzheimer's treatment fails. PMID- 27003341 TI - Stem cell therapy for a debilitating retinal disorder. PMID- 27003343 TI - A mechanism for inherited metabolic disorders. PMID- 27003346 TI - Considering the risks and safety of intraperitoneal injections. PMID- 27003344 TI - A novel adjuvant promises improved rabies vaccine. PMID- 27003347 TI - A miniscule model for research. PMID- 27003348 TI - A review of USDA enforcement actions in 2014. PMID- 27003349 TI - Collaboration requires mutual understanding. PMID- 27003350 TI - Too many IACUCs in the kitchen. PMID- 27003351 TI - Naked transparency in communication. PMID- 27003352 TI - Roles and Responsibilities. PMID- 27003353 TI - Aspects of the husbandry and management of captive cervids. AB - In a continuing effort to better understand the transmission and persistence of chronic wasting disease in wild populations of cervids, Colorado State University, Fort Collins houses two species of deer indoors to study the pathogenesis of chronic wasting disease. Here we report key aspects regarding the husbandry and medication of Reeves' muntjac and white-tailed deer in captivity for research purposes. PMID- 27003354 TI - Differences in the estrous cycles of Goto-Kakizaki and Wistar rats. AB - Goto-Kakizaki rats are an important model of type 2 diabetes, but it is difficult to maintain and expand colonies of these rats because they exhibit poor fertility. In this work, we studied the estrous cycle of Goto-Kakizaki and Wistar rats to characterize differences that might underlie these reproductive difficulties. We monitored rats from weaning to vaginal opening to assess pubertal development, and we monitored the estrous cycle and basal glycemia of each rat for 20 days at 1 month of age and at 6 months of age. At an early age we found no differences between Goto-Kakizaki and Wistar rats with respect to the onset of puberty or the periodicity of the estrous cycle. However, at 6 months Goto-Kakizaki rats spent more time in proestrus and less time in estrus each cycle, compared to Wistar rats. This delay in proceeding from proestrus to estrus could reflect a dysregulation of the hypothalamic-pituitary-gonadal axis, accompanying progression of the diabetic condition. It might also cause anovulatory cycles, which could explain the reduced reproductive capacity of Goto Kakizaki rats. PMID- 27003355 TI - Outreach: managers need to do it. PMID- 27003356 TI - Sharing our work with pride. PMID- 27003357 TI - Use of point-of-care tests among general practitioners: a cross-sectional study in Saxony, Germany. AB - INTRODUCTION: There is little knowledge about the use of point-of-care (POC) tests among general practitioners (GPs). The aim of this study was to determine which POC tests are known and used by GPs and how they estimate the usefulness of those tests. The use of POC tests among GPs and university-associated general practitioners who teach undergraduates (GPTUs) was elucidated. Differences between GPs working in urban and rural areas were also investigated. METHODS: The knowledge, utilisation and usefulness (as estimated by the responders) of 27 POC tests were assessed with a self-designed questionnaire in a random sample of GPs (n=244) and GPTUs (n=48) in Saxony, Germany. RESULTS: A total of 63 GPs and 31 GPTUs (response rates 26.5% and 64.6%, respectively) responded. No relevant difference between GPs and GPTUs was found. The GPs were familiar with 22.5+/-4.5 (mean +/- standard deviation) of the laboratory parameters, the GPTUs with 22.9+/ 4.3 (p=0.427). The amount of recognised POC tests was 11.6+/-4.9 vs 12.4+/-5.5 (GPs vs GPTUs; p=0.441). The amount of utilised POC tests was 5.5+/-2.3 vs 6.0+/ 2.5 (GPs vs GPTUs; p=0.431). Rural GPs were familiar with more POC tests than urban GPs (mean number of tests (rural vs urban): 13.3+/-5.5 vs 10.6+/-4.4; p=0.011), but there was no difference in the amount of utilised POC tests. Twelve of the 27 POC tests were estimated as useful by more than 50% of the responders who answered this item. CONCLUSIONS: Only a limited number of rapid tests are estimated as useful and are used by GPs in Saxony. PMID- 27003358 TI - The Effect of Lipopolysaccharide Core Oligosaccharide Size on the Electrostatic Binding of Antimicrobial Proteins to Models of the Gram Negative Bacterial Outer Membrane. AB - Understanding the electrostatic interactions between bacterial membranes and exogenous proteins is crucial to designing effective antimicrobial agents against Gram-negative bacteria. Here we study, using neutron reflecometry under multiple isotopic contrast conditions, the role of the uncharged sugar groups in the outer core region of lipopolysaccharide (LPS) in protecting the phosphate-rich inner core region from electrostatic interactions with antimicrobial proteins. Models of the asymmetric Gram negative outer membrane on silicon were prepared with phopshatidylcholine (PC) in the inner leaflet (closest to the silicon), whereas rough LPS was used to form the outer leaflet (facing the bulk solution). We show how salt concentration can be used to reversibly alter the binding affinity of a protein antibiotic colicin N (ColN) to the anionic LPS confirming that the interaction is electrostatic in nature. By examining the interaction of ColN with two rough LPS types with different-sized core oligosaccharide regions we demonstrate the role of uncharged sugars in blocking short-range electrostatic interactions between the cationic antibiotics and the vulnerable anionic phosphate groups. PMID- 27003359 TI - Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease. AB - Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury. PMID- 27003360 TI - Rainbow trout CK9, a CCL25-like ancient chemokine that attracts and regulates B cells and macrophages, the main antigen presenting cells in fish. AB - CK9 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to mammalian CCL25. Although CK9 is known to be transcriptionally regulated in response to inflammation particularly in mucosal tissues, its functionality has never been revealed. In the current work, we have demonstrated that CK9 is chemoattractant for antigen presenting cells (APCs) expressing major histocompatibility complex class II (MHC II) on the cell surface. Among these APCs, CK9 has a strong chemotactic capacity for both B cells (IgM+ and IgT+) and macrophages. Along with its chemotactic capacities, CK9 modulated the MHC II turnover of B lymphocytes and up-regulated the phagocytic capacity of both IgM+ cells and macrophages. Although CK9 had no lymphoproliferative effects, it increased the survival of IgT+ lymphocytes. Furthermore, we have established that the chemoattractant capacity of CK9 is strongly increased after pre-incubation of leukocytes with a T-independent antigen, whereas B cell receptor (BCR) cross linking strongly abrogated their capacity to migrate to CK9, indicating that CK9 preferentially attracts B cells at the steady state or under BCR-independent stimulation. These results point to CK9 being a key regulator of B lymphocyte trafficking in rainbow trout, able to modulate innate functions of teleost B lymphocytes and macrophages. PMID- 27003361 TI - TGF-beta1-Smad signaling pathways are not required for epidermal LC homeostasis. PMID- 27003362 TI - Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC. AB - Eukaryotic translation initiation factor 4 gamma 1(EIF4G1) is related to tumorigenesis and tumor progression. However, its role and the underlying mechanisms in the regulation of tumor development in non-small cell lung cancers (NSCLC) remain largely unknown. Here we report that the levels of EIF4G1 expression are much higher in NSCLC cell lines and tumor tissues than those in the normal lung cells and adjacent normal tissues from the same patients. Using shRNA to knock down EIF4G1 expression stably, we found EIF4G1 required for NSCLC cell proliferation, anchorage-independent growth, migration and invasion. Furthermore, silencing of EIF4G1 induces NSCLC cell apoptosis and causes G0/G1 cell cycle arrest. To identify the partner protein network of EIF4G1 in NSCLC cells, we found that Ubiquitin-specific protease 10 (USP10) can directly interacts with EIF4G1, while acting as a negative regulator for EIF4G1-mediated functions. Together, our results indicate that EIF4G1 functions as an oncoprotein during NSCLC development, which may represent a novel and promising therapeutic target in lung cancer. PMID- 27003364 TI - Cheilitis in acne vulgaris patients with no previous use of systemic retinoid products. AB - BACKGROUND/OBJECTIVES: Isotretinoin is commonly used in the treatment of acne vulgaris. While one of the more common side-effects is cheilitis, we have observed an increased incidence of cheilitis prior to the commencement of systemic isotretinoin. The aim of this study was to assess the prevalence of cheilitis among acne vulgaris patients. METHODS: A non-interventional cross sectional study of patients with acne vulgaris. Patients with previous use of systemic retinoids were excluded. The patients were examined for signs and symptoms of cheilitis. RESULTS: Of a total of 400 patients, 134 (34%) had evidence of cheilitis at initial presentation. Two-thirds (63%) were female (P < 0.001). The distribution of the cheilitis was as follows; 55% on the lower lip, 30% on both lips, and 16% on the upper lip. Over a quarter (27%) of patients with cheilitis had acne excorie, compared with only 8% of patients with no signs of cheilitis. CONCLUSION: Our findings suggest that cheilitis is quite common among acne vulgaris patients even before treatment with isotretinoin. PMID- 27003363 TI - Prospective phase II trial of pazopanib plus CapeOX (capecitabine and oxaliplatin) in previously untreated patients with advanced gastric cancer. AB - We designed a single-arm, open label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx (capecitabine and oxaliplatin) in metastatic /recurrent advanced gastric cancer (AGC) patients. Previously untreated AGC patients received capecitabine (850 mg/m2 bid, day 1-14) plus oxaliplatin (130 mg/m2, day 1) in combination with pazopanib (800 mg, day 1 21) every three weeks. Treatment was continued until progression of the disease or intolerable toxicity was observed. In all, 66 patients were treated with pazopanib plus CapeOx. The median age of the patients was 51.5 years (range, 23.0 77), and the median ECOG performance status was 1 (0-1). Among all 66 patients, one complete response and 37 partial responses were observed (overall response rate, 62.4%; 95% confidence interval (CI), 45.7-73.5% accounting for the 2-stage design of this trial). Stable disease was observed in 23 patients (34.8%), revealing a 92.4% disease control rate. The median progression free survival and overall survival were 6.5 months (95% CI, 5.6-7.4) and 10.5 months (95% CI, 8.1 12.9), respectively. Thirty-four patients (51.5%) experienced a treatment-related toxicity of grade 3 or more. The most common toxicities of grade 3 or more were neutropenia (15.1%), anemia (10.6%), thrombocytopenia (10.6%), anorexia (7.6%), nausea (3.0%), and vomiting (3.0%). There were no treatment-related deaths. The combination of pazopanib and CapeOx showed moderate activity and an acceptable toxicity profile as a first-line treatment in metastatic / recurrent AGC patients (ClinicalTrials.gov NCT01130805). PMID- 27003365 TI - Presence of heavy metals in fruits and vegetables: Health risk implications in Bangladesh. AB - The presence of toxic heavy metals such as As, Cd, Pb, Cr, Mn, Ni, Cu, and Zn in nationally representative samples of highly consumed fruits and vegetables was determined by inductively coupled plasma mass spectrometry (ICP-MS). Their concentrations exceeded the maximum allowable concentration (MAC) set by FAO/WHO for Pb in mango and Cd in tomato among the analyzed fruits and vegetables. Pb content in mango was found to be six times higher than the safe limit at production level. Health risks associated with the intake of these metals were evaluated in terms of estimated daily intake (EDI), and carcinogenic and noncarcinogenic risks by target hazard quotient (THQ) and hazard index (HI). EDI values of all the metals were found to be below the maximum tolerable daily intake (MTDI). The THQs of all metals were <1, suggesting no health hazards for adult population. However, total THQs of Mn and Cu were >1 through consumption of all vegetables, indicating significant health risks. HI was found to be <1 (0.825) for consumption of fruits; however, it was >1 (3.727) for vegetable consumption, suggesting adverse health effects from vegetable consumption only. The total carcinogenic risk (CR) of As was below the threshold level (10(-6)) and 9.82E-05 for Pb, suggesting no potential CR from As consumption, but indicating the risk of Pb-induced carcinogenesis. The findings of this study reveal the health risks associated with the consumption of heavy metals through the intake of selected fruits and vegetables in adult population of Bangladesh. PMID- 27003366 TI - Impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased. AB - Groundwater quality deterioration has attracted world-wide concerns due to its importance for human water supply. Although more and more studies have shown that human activities and climate are changing the groundwater status, an investigation on how different groundwater heavy metals respond to human activity modes (e.g. mining, waste disposal, agriculture, sewage effluent and complex activity) in a varying climate has been lacking. Here, for each of six heavy metals (i.e. Fe, Zn, Mn, Pb, Cd and Cu) in groundwater, we use >330 data points together with mixed-effect models to indicate that (i) human activity modes significantly influence the Cu and Mn but not Zn, Fe, Pb and Cd levels, and (ii) annual mean temperature (AMT) only significantly influences Cu and Pb levels, while annual precipitation (AP) only significantly affects Fe, Cu and Mn levels. Given these differences, we suggest that the impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased. PMID- 27003367 TI - Influence of UVB radiation on the lethal and sublethal toxicity of dispersed crude oil to planktonic copepod nauplii. AB - Toxic effects of petroleum to marine zooplankton have been generally investigated using dissolved petroleum hydrocarbons and in the absence of sunlight. In this study, we determined the influence of natural ultraviolet B (UVB) radiation on the lethal and sublethal toxicity of dispersed crude oil to naupliar stages of the planktonic copepods Acartia tonsa, Temora turbinata and Pseudodiaptomus pelagicus. Low concentrations of dispersed crude oil (1 MUL L(-1)) caused a significant reduction in survival, growth and swimming activity of copepod nauplii after 48 h of exposure. UVB radiation increased toxicity of dispersed crude oil by 1.3-3.8 times, depending on the experiment and measured variables. Ingestion of crude oil droplets may increase photoenhanced toxicity of crude oil to copepod nauplii by enhancing photosensitization. Photoenhanced sublethal toxicity was significantly higher when T. turbinata nauplii were exposed to dispersant-treated oil than crude oil alone, suggesting that chemical dispersion of crude oil may promote photoenhanced toxicity to marine zooplankton. Our results demonstrate that acute exposure to concentrations of dispersed crude oil and dispersant (Corexit 9500) commonly found in the sea after oil spills are highly toxic to copepod nauplii and that natural levels of UVB radiation substantially increase the toxicity of crude oil to these planktonic organisms. Overall, this study emphasizes the importance of considering sunlight in petroleum toxicological studies and models to better estimate the impact of crude oil spills on marine zooplankton. PMID- 27003368 TI - Preconceptional, prenatal and postnatal exposure to outdoor and indoor environmental factors on allergic diseases/symptoms in preschool children. AB - BACKGROUND: Environmental factors have been found to be associated with allergic diseases, but it is unclear which environmental factor during which exposure window causes what kind of allergic diseases. OBJECTIVES: We investigated association between exposure to some predominant outdoor and indoor environmental factors during preconceptional, prenatal, and postnatal periods and allergic diseases/symptoms in 2598 children in China. METHODS: Children's lifetime incidence of allergic diseases and current prevalence of allergic symptoms and exposure to indoor new furniture/redecoration and mold/dampness was surveyed by a questionnaire. Exposure to outdoor air pollutants was estimated by the concentrations measured at air quality monitoring stations. Multiple logistic regression model was used to evaluate the associations between outdoor air pollutants and indoor environmental factors and allergic diseases (asthma, allergic rhinitis, and eczema) and symptoms (wheezing, night cough, and rhinitis like). RESULTS: We found that preconceptional, prenatal, and postnatal exposure to outdoor industrial and traffic air pollutants were significantly associated with increase in the risk of childhood asthma, and also positively associated with allergic rhinitis and eczema. However, we cannot distinguish the effect of outdoor air pollutants and exposure windows because of their high correlations. New furniture was associated with eczema and allergic rhinitis during postnatal exposure, but redecoration associated with asthma and eczema during prenatal exposure. Indoor visible mold/damp stains was significant for eczema during prenatal exposure and asthma during postnatal exposure respectively, but window condensation was significant for all childhood allergic diseases during both prenatal and postnatal exposures. Allergic symptoms in children were found to be associated with exposure to indoor factors only. CONCLUSIONS: Associations between outdoor air pollutants and indoor environmental factors and childhood allergic diseases/symptoms were divergent and related to the timing of exposure. PMID- 27003369 TI - Rotenone causing dysfunctional mitochondria and lysosomes in cerebral ganglions of Lumbricus terrestris degenerate giant fibers and neuromuscular junctions. AB - Rotenone is well-documented to cause neurodegenerative condition such as Parkinson's, in the exposed systems. However, its detrimental effect on particular sites of neuronal pathway is still under investigation. We aimed at elucidating the impact of rotenone on cerebral ganglions (CG) of Lumbricus terrestris which control movement and behaviour of the worms. Worms were exposed to 0-0.4 ppm/mL of rotenone. Mitochondrial and lysosomal integrities were found to be affected beyond 0.2 ppm/mL of rotenone. Activities of cholinergic enzymes and the expression of tyrosine hydroxylase showed an impaired neuronal transmission in CGs at the dose of 0.2 ppm/mL of rotenone. Histopathological and immunoflourescent analyses showed neuronal apoptosis, reduced nucleic acid content and inhibited of neurosecretion at 0.3 ppm/mL. Electron microscopy showed that the neurons and neuromuscular junctions were affected at 0.2 ppm/mL. Dose dependent changes were also observed in the motor function such as burrowing behaviours and locomotion. Conduction velocity (CV) and locomotion assessment showed that the CV of lateral giant fiber (LGF) was reduced while that of MGF remains unaffected at 0.2 ppm, the dose at which the burrowing behaviour was also not affected. LGF, cholinergic enzymes and tyrosine hydroxylase are primarily targeted by rotenone affecting locomotion at 0.2 ppm/mL while MGF, neuropile and the burrowing behaviour were affected at 0.3 ppm/mL. We demonstrate, in addition to dose-dependent effects, that the bioaccumulation factors range 0.28-0.32 ppm/MUg of rotenone cause degenerative impact on giant fibers affecting neuronal behaviors/locomotion of worms. We also propose worms for studying mechanisms of neuronal pathology caused by chemicals prevailing in earth's atmosphere. PMID- 27003370 TI - Monitoring of (7)Be and gross beta in particulate matter of surface air from Mallorca Island, Spain. AB - Measurements of airbone radionuclides (7)Be and gross beta (Abeta) jointly with atmospheric aerosols, i.e. particulate matter (PM) were routinely carried out for 10 years (2004-2014) at the University of the Balearic Islands, Spain. A total of 728 filter (0.8 MUm pore size) samples were collected, and in all of them (7)Be and Abeta specific activities were detected. The maximum and minimum specific activities monitored were 0.73 +/- 0.41 - 15.8 +/- 1.26 mBq m(-3) of (7)Be and 0.14 +/- 0.02 - 2.55 +/- 0.04 mBq m(-3) of Abeta. PM concentrations were also determined, showing seasonal behavior with the highest concentration in summer and the lowest one in winter. Several meteorological parameters have been considered to explain this intra-annual variation. Principal component analysis (PCA) was applied to the dataset indicating that it is well represented by two principal components that explain 76.6% of total variance. Additionally, a second study with preliminary results of the specific activities of two natural radiotracers ((7)Be and (210)Pb) in PM10 samples was carried out. They were monitored for two years (2013-2015) in air of Mallorca Island. (7)Be and (210)Pb were detected in most of the PM10 filters, in 100% and 93% of them, respectively. The relationship between activities of both radionuclides and several relevant meteorological parameters was established at 95% confidence level. As a common result to PM and PM10 samples, a strong positive correlation between the evaluated radionuclides and temperature was found. PMID- 27003371 TI - Hollow mesoporous TiO2 microspheres for enhanced photocatalytic degradation of acetaminophen in water. AB - Hollow core-shell mesoporous TiO2 microspheres were synthesized by a template free solvothermal route for efficient photocatalytic degradation of acetaminophen. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Barrett-Joyner-Halenda data revealed a micrometer-sized mesoporous anatase TiO2 hollow sphere with large surface area and efficient light harvesting. For the photocatalytic degradation of acetaminophen in 60 min, the conversion fraction of the drug increased from 88% over commercial Degussa P25 TiO2 to 94% over hollow spheres with about 25% increase in the initial reaction rate. Even after 10 repeated runs, the recycled hollow spheres showed good photodegradation activity. The intermediates generated in the photocatalytic reactions were eventually converted into molecules that are easier to handle. The simple fabrication route would facilitate the development of photocatalysts for the decomposition of environmental contaminants. PMID- 27003372 TI - The toxic effect and bioaccumulation in aquatic oligochaete Limnodrilus hoffmeisteri after combined exposure to cadmium and perfluorooctane sulfonate at different pH values. AB - Cadmium (Cd) and Perfluorooctane sulfonate (PFOS) have been detected in aquatic environment. In this study, we investigated the acute effect, bioaccumulation and oxidative stress status in the aquatic oligocheate Limnodrilus hoffmeisteri after exposure to Cd and PFOS at different pH values. In the studied pH range, acute Cd toxicity was significantly enhanced with pH increasing from 6.2 to 8.0, and the 48h-EC50 of Cd was (significantly) decreased in the presence of PFOS. Bioaccumulation analysis results show that the accumulated Cd/PFOS in single exposure group increased with increasing exposure concentrations, and co-exposure makes internal Cd concentration significantly lowered for Cd(0.1) group at pH 8.0. Significant changes in superoxide dismutase activity, glutathione level and malondialdehyde content were observed in single and combined treatments. Based on IBR value, single Cd and PFOS exposure caused largest damage to the antioxidant defense system at pH 8.0 and pH 6.2, respectively, while the harmful effects of joint exposure were always the "compromise" between single Cd and PFOS exposure. This work could provide useful information for the risk assessment of co-exposure to perfluorinated compounds and heavy metals in natural environment. PMID- 27003373 TI - An increased CDT camouflaged a monoclonal light chain gammopathy: An approach for diagnosis. AB - INTRODUCTION: Carbohydrate-deficient transferrin (CDT) is the most reliable indicator for the detection of chronic alcohol consumption. Recently, we have investigated a clinical case in which a concomitant monoclonal light chain gammopathy mimicked an increase of this biomarker. MATERIALS AND METHODS: A patient's serum was routinely examined by capillary electrophoresis (CE) for evaluation of CDT, and it was subsequently analysed through high-performance liquid chromatography (HPLC) to confirm the referred result. Then, according to the patient's clinical history, we performed serum and urine immunofixation, together with k and lambda free light chain measurement. RESULTS: The pathological CDT value obtained by CE agreed with the patient's previous data, but it was not confirmed by the HPLC. The patient's medical record revealed hypogammaglobulinaemia since 2006, which had been recently examined by a haematological visit. Serum and urine immunofixation revealed a light chain gammopathy, which had been suspected but never confirmed by laboratory assessment. The k and lambda free light chain measurement completed the diagnostic process. CONCLUSION: To the best of the authors' knowledge, this is the first study of its kind to report on a perfect camouflaging of a monoclonal light chain as disialo-transferrin. The importance of the careful examination of the patient's clinical history for the correct evaluation of laboratory results, thereby preventing misinterpretations, is also highlighted. PMID- 27003374 TI - Noradrenergic modulation of emotional memory in aging. AB - Interest in the role of the noradrenergic system in the modulation of emotional memories has recently increased. This study briefly reviews this timely line of research with a specific focus on aging. After having identified surprisingly few studies that investigated emotional memory in older adults from a neurobiological perspective, we found a significant interaction between noradrenergic activity and emotional memory enhancement in older adults. This pattern of data are explained both in terms of a top-down modulation of behavioral processes (e.g., changes in priority and individual goals) and in terms of greater activity of noradrenergic system during aging. Altogether, both behavioral and genetic variations studies (e.g., Alpha 2 B Adrenoceptor genotype) have shown that healthy older adults are able to circumvent or minimize the experience of negative emotions and stabilize or even enhance positive emotional experiences. Future studies are highly warranted to better clarify the relationship between noradrenaline and emotional memories in the aging brain. PMID- 27003375 TI - Left bundle branch block, chest pain and catheterization laboratory activation: an unavoidable cascade reaction? AB - Identification of acute myocardial infarction (AMI) in the presence of left bundle branch block (LBBB) remains challenging. European guidelines recommend prompt reperfusion therapy in patients with suspected ongoing myocardial ischemia and new or presumably new LBBB, whereas AHA/ACC guidelines state that LBBB should not be considered diagnostic of AMI in isolation. Sgarbossa criteria and their recent modified version with the introduction of ST/S ratio can be helpful in this setting. A clinical-instrumental algorithm to manage suspected AMI in the presence of LBBB has been recently proposed. We present five paradigmatic clinical cases. PMID- 27003376 TI - Disorder-specific versus transdiagnostic and clinician-guided versus self-guided internet-delivered treatment for panic disorder and comorbid disorders: A randomized controlled trial. AB - Transdiagnostic cognitive behaviour therapy (TD-CBT) aims to target the symptoms of multiple disorders whereas disorder-specific CBT (DS-CBT) targets the symptoms of principal disorders. This study compared the relative benefits of internet delivered TD-CBT and DS-CBT when provided in clinician-guided (CG-CBT) and self guided (SG-CBT) formats for people with a principal diagnosis of Panic Disorder (PD). Participants (n=145) were randomly allocated to receive TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of PD (Cohen's d >= 0.71; avg. reduction >= 36%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen's d >= 0.71; avg. reduction >= 33%), generalised anxiety disorder (Cohen's d >= 0.91; avg. reduction >= 34%) and social anxiety disorder (Cohen's d >= 0.50; avg. reduction >= 15%) were found over the 24-month follow-up period. Highlighting their efficacy and acceptability, no marked and consistent differences were observed between TD-CBT and DS-CBT or CG-CBT and DS-CBT. PMID- 27003378 TI - First molecular survey and identification of Anaplasma spp. in white yaks (Bos grunniens) in China. AB - Anaplasmosis is caused by a group of obligate intracellular bacteria in the genus Anaplasma, which are transmitted by ticks and infect humans, domestic animals and wildlife. This study was conducted to determine the prevalence and molecular characterization of Anaplasma spp. in semi-wild white yaks sampled in Tianzhu Tibetan Autonomous County, northwest China. Out of 332 samples tested, 35 (10.9%) were positive for Anaplasma spp. The positive rates were 6.2% (20/322) and 5.3% (17/322) for Anaplasma bovis and Anaplasma phagocytophilum in white yaks, respectively. None of the sample was positive for Anaplasma marginale. Two (0.6%) samples were simultaneously positive to A. bovis and A. phagocytophilum. Sequence analysis of the 16S rRNA gene revealed two genotypes (ApG1 and ApG2) of A. phagocytophilum and two sequence types (ST1 and ST2) of A. bovis in white yaks. This study is the first to document the presence of Anaplasma in white yaks. Our findings extend the host range for Anaplasma species and provide more valuable information for the control and management of anaplasmosis in white yaks. PMID- 27003379 TI - Exploring the use of Generalized Indirect Covariance to reconstruct pure shift NMR spectra: Current Pros and Cons. AB - The current Pros and Cons of a processing protocol to generate pure chemical shift NMR spectra using Generalized Indirect Covariance are presented and discussed. The transformation of any standard 2D homonuclear and heteronuclear spectrum to its pure shift counterpart by using a reference DIAG spectrum is described. Reconstructed pure shift NMR spectra of NOESY, HSQC, HSQC-TOCSY and HSQMBC experiments are reported for the target molecule strychnine. PMID- 27003380 TI - Spectral density mapping at multiple magnetic fields suitable for (13)C NMR relaxation studies. AB - Standard spectral density mapping protocols, well suited for the analysis of (15)N relaxation rates, introduce significant systematic errors when applied to (13)C relaxation data, especially if the dynamics is dominated by motions with short correlation times (small molecules, dynamic residues of macromolecules). A possibility to improve the accuracy by employing cross-correlated relaxation rates and on measurements taken at several magnetic fields has been examined. A suite of protocols for analyzing such data has been developed and their performance tested. Applicability of the proposed protocols is documented in two case studies, spectral density mapping of a uniformly labeled RNA hairpin and of a selectively labeled disaccharide exhibiting highly anisotropic tumbling. Combination of auto- and cross-correlated relaxation data acquired at three magnetic fields was applied in the former case in order to separate effects of fast motions and conformational or chemical exchange. An approach using auto correlated relaxation rates acquired at five magnetic fields, applicable to anisotropically moving molecules, was used in the latter case. The results were compared with a more advanced analysis of data obtained by interpolation of auto correlated relaxation rates measured at seven magnetic fields, and with the spectral density mapping of cross-correlated relaxation rates. The results showed that sufficiently accurate values of auto- and cross-correlated spectral density functions at zero and (13)C frequencies can be obtained from data acquired at three magnetic fields for uniformly (13)C-labeled molecules with a moderate anisotropy of the rotational diffusion tensor. Analysis of auto-correlated relaxation rates at five magnetic fields represents an alternative for molecules undergoing highly anisotropic motions. PMID- 27003381 TI - Fertility awareness-based mobile application for contraception. AB - OBJECTIVES: The aim of the study was to retrospectively evaluate the effectiveness of a fertility awareness-based method supported by a mobile-based application to prevent unwanted pregnancies as a method of natural birth control. METHODS: In a retrospective analysis, the application's efficiency as a contraceptive method was examined on data from 4054 women who used the application as contraception for a total of 2085 woman-years. RESULTS: The number of identified unplanned pregnancies was 143 during 2053 woman-years, giving a Pearl Index of 7.0 for typical use. Ten of the pregnancies were due to the application falsely attributing a safe day within the fertile window, producing a perfect-use Pearl Index of 0.5. Calculating the cumulative pregnancy probability by life-table analysis resulted in a pregnancy rate of 7.5% per year (95% confidence interval 5.9%, 9.1% per year). CONCLUSIONS: The application appears to improve the effectiveness of fertility awareness-based methods and can be used to prevent pregnancies if couples consistently protect themselves on fertile days. PMID- 27003382 TI - Pigment Epithelium-Derived Factor Inhibits Oxygen-Induced Retinal Neovascularization in a Murine Model. AB - BACKGROUND: The inhibitory effects of pigment epithelium-derived factor (PEDF) on retinal neovascularization were observed in a murine model of oxygen-induced retinopathy. METHODS: PEDF was administered via intravitreal injection into the right eye of mice subjected to hyperoxia. The proliferative neovascular response was assessed by evaluating the vascular pattern in retinal flat-mounts and quantified by counting the number of new vascular cell nuclei extending into the internal limiting membrane. Retinas were stained for vascular endothelial growth factor (VEGF), PEDF, and CD31 with immunohistochemical method. RESULTS: The effect of PEDF on retinal neovascularization is related to the postnatal age at the time of injection and the number of injections. The injection of 2 ug of PEDF at postnatal day 12 (P12) and P14 markedly inhibited retinal neovascularization. CONCLUSION: Locally administered PEDF is a potentially effective vascular inhibitory factor for the treatment and prevention of retinopathy of prematurity. PMID- 27003383 TI - Role of kisspeptin in polycystic ovary syndrome (PCOS). AB - OBJECTIVE: Due to the complex relationship between kisspeptin and the hypothalamic-pituitary-gonadal axis, the study was planned to measure the kisspeptin levels in polycystic ovary syndrome (PCOS) and to analyze the correlations between kisspeptin and PCOS-related reproductive, metabolic changes. METHODS: The study was designed as a prospective study in Dokuz Eylul University between December 2011 and September 2013. A total of 285 PCOS cases and 162 controls were recruited. After the antropometric measeruments and physcial examination, blood samples were taken for biochemical analysis. RESULTS: PCOS group's mean BMI was 24.32 +/- 3.40 and for the control group, BMI value was 23.44 kg/m2 +/- 4.08 (p = 0.351). PCOS patients' FSH level was 5.10 +/- 2.01 mIU/L, LH value was 7.75 +/- 4.31 mIU/mL, LH/FSH ratio was 1.70 +/- 1.28, DHEAS value was 221.84 +/- 105.02 mg/dl, total testosterone value was 50.51 +/- 27.93 ng/ml, free testosterone value was 2.52 +/- 1.05 pg/ml, SHBG was 63.74 +/- 45.62 nmol/L, LDL was 102.56 +/- 23.45 mg/dL, HDL value was 51.36 +/- 12.15 mg/dL, total cholesterol value was 214.85 +/- 39.27 mg/dL, triglyceride value was 112.95 +/- 46.88 mg/dL, Apo A1 value was 171.30 +/- 35.35 mg/dL, Apo B value was 71.08 +/- 19.07 mg/dL, Apo B/A1 ratio was 0.42 +/- 0.14, free androgen index was 13.77 +/- 14.15, fasting glucose value was 80.68 +/- 13.80 mg/dL, fasting insulin levels was 14.13 +/- 9.11 MUiU/mL, HOMA-IR index was 2.76 +/- 2.34, AMH value was 5.93 +/- 3:33 in ng/ml, and found to be significantly higher (p < 0.001). Leptin value was 9.71 +/- 5.54 pg/ml and kisspeptin value was 1.92 +/- 1.29 ng/ml, respectively. Kisspeptin and leptin levels showed no statistically significant difference with control group and PCOS group. In all PCOS patients, kisspeptin showed positive correlations between LH and leptin levels. CONCLUSION: In this study, kisspeptin had a positive correlation with LH and leptin levels in PCOS. In fact, the serum levels of kisspeptin and leptin does not differ statistically between PCOS and healthy women. There are limited data in the literature with regard to changes in kisspeptin levels and its relation with metabolic and hormonal disturbances. PMID- 27003385 TI - Sleep and cancer: Synthesis of experimental data and meta-analyses of cancer incidence among some 1,500,000 study individuals in 13 countries. AB - Sleep and its impact on physiology and pathophysiology are researched at an accelerating pace and from many different angles. Experiments provide evidence for chronobiologically plausible links between chronodisruption and sleep and circadian rhythm disruption (SCRD), on the one hand, and the development of cancer, on the other. Epidemiological evidence from cancer incidence among some 1 500 000 study individuals in 13 countries regarding associations with sleep duration, napping or "poor sleep" is variable and inconclusive. Combined adjusted relative risks (meta-RRs) for female breast cancer, based on heterogeneous data, were 1.01 (95% CI: 0.97-1.06). Meta-RRs for cancers of the colorectum and of the lung in women and men and for prostate cancer were 1.08 (95% CI: 1.03-1.13), 1.11 (95% CI: 1.00-1.22) and 1.05 (95% CI: 0.83-1.33), respectively. The significantly increased meta-RRs for colorectal cancer, based on homogeneous data, warrant targeted study. However, the paramount epidemiological problem inhibiting valid conclusions about the associations between sleep and cancer is the probable misclassification of the exposures to facets of sleep over time. Regarding the inevitable conclusion that more research is needed to answer How are sleep and cancer linked in humans? we offer eight sets of recommendations for future studies which must take note of the complexity of multidirectional relationships. PMID- 27003386 TI - Painful lateral foot swelling. Diagnosis. PMID- 27003384 TI - Single-cell lineage tracking analysis reveals that an established cell line comprises putative cancer stem cells and their heterogeneous progeny. AB - Mammalian cell culture has been used in many biological studies on the assumption that a cell line comprises putatively homogeneous clonal cells, thereby sharing similar phenotypic features. This fundamental assumption has not yet been fully tested; therefore, we developed a method for the chronological analysis of individual HeLa cells. The analysis was performed by live cell imaging, tracking of every single cell recorded on imaging videos, and determining the fates of individual cells. We found that cell fate varied significantly, indicating that, in contrast to the assumption, the HeLa cell line is composed of highly heterogeneous cells. Furthermore, our results reveal that only a limited number of cells are immortal and renew themselves, giving rise to the remaining cells. These cells have reduced reproductive ability, creating a functionally heterogeneous cell population. Hence, the HeLa cell line is maintained by the limited number of immortal cells, which could be putative cancer stem cells. PMID- 27003387 TI - Fibrodysplasia ossificans progressiva: initial presentation with a preosseous lesion of the scalp and its MRI appearance. AB - This case subject is a 1-year-old girl presenting with recurrent diffuse soft tissue swelling of the scalp and periorbital region. Her family denied any known history of trauma. There was no obvious discoloration or local heat at the lesion. Magnetic resonance imaging (MRI) revealed diffuse soft tissue swelling of the scalp manifesting as high signal intensity on T2-weighted images and low signal intensity on T1-weighted images with diffuse enhancement after gadolinium contrast administration. Biopsy yielded inconclusive pathological results. Fibrodysplasia ossificans progressiva (FOP) was not suspected until malformation of the patient's toes was noticed. The scalp lesion underwent spontaneous regression, and subsequent radiographs of the chest and cervical spine revealed heterotopic ossifications of the neck and thorax. Early diagnosis of FOP is vital because trauma, unnecessary biopsy and intramuscular injection are known to cause acceleration of heterotopic ossifications. Previous studies reported diffuse soft tissue swelling at the posterior neck, thoracic wall or paraspinal region as preosseous lesions of FOP (Shiva Kumar et al. Neurology. 2010;74(6):e20, Merchant et al. Pediatr Radiol. 2006;36(10):1108-11, Hagiwara et al. AJR Am J Roentgenol. 2003;181(4):1145-7). To our knowledge, diffuse soft tissue swelling of the scalp as a preosseous lesion of FOP and associated MRI findings have not yet been reported. We believe that awareness of preosseous lesions presenting as diffuse soft tissue swelling, in addition to shortening and valgus deformity of the great toes, is an important diagnostic clue for establishing FOP. PMID- 27003388 TI - How did medicaid expansions affect labor supply and welfare enrollment? Evidence from the early 2000s. AB - In the early 2000s, Arizona, Maine, New Mexico, New York, Oregon, and Vermont expanded Medicaid to cover more low-income individuals, primarily childless adults. This change provides the researcher with an opportunity to analyze the effects of these expansions on labor supply and welfare enrollment. I use a large data set of 176 counties over 7 years, including 3 years of pre-expansion period, 1 year of implementation year, and 3 years of post-expansion period. Using a difference-in-differences approach, I find the most-affected counties had a 1.4 percentage-point more decline in labor force participation rate in comparison to other counties. Furthermore, I observe a 0.32 h decrease in average weekly hours and a 1.1 % increase in average weekly wages. This indicates labor supply was affected more than labor demand. I also observe a 0.49 % increase in Supplemental Nutrition Assistance Program (SNAP) enrollment after the Medicaid expansions. These results are robust to an alternative identification of the most-affected counties, inclusion of counties from comparison states, limiting the control group to only high-poverty counties from comparison states, exclusion of county specific time trends, and different configuration of clustered errors. My findings provide early insights on the potential effects of new Medicaid expansions of the Affordable Care Act (ACA), since 82 % of those newly eligible are expected to be childless adults. PMID- 27003389 TI - Deconvoluting the relationships between autophagy and metastasis for potential cancer therapy. AB - Autophagy is a highly conserved lysosome-dependent degradation process that may digest some long-lived proteins and damaged organelles. As an essential homeostasis maintaining system in normal cells, autophagy plays a key role in several pathological settings, especially cancer. Metastasis, known as a crucial hallmark of cancer progression, is the primary cause of cancer lethality. The role of autophagy in metastasis is quite complex as supportive evidence has indicated both pro-metastatic and anti-metastatic functions of autophagy. Autophagy can inhibit metastasis by restricting necrosis and mediating autophagic cell death, whereas it may also promote metastasis by enhancing cancer cell fitness in response to stress. Moreover, the function of autophagy is context- and stage-dependent. Specifically, during the early steps of metastasis, autophagy mainly serves as a suppressor, while it plays a pro-metastatic role in the later steps. Here, we focus on highlighting the dual roles of autophagy in metastasis and address the molecular mechanisms involved in this process, which may provide a new insight into cancer biology. While, we also summarize several anti-metastatic agents manipulating autophagy, in the hope of shedding light on exploration of potential novel drugs for future cancer therapy. PMID- 27003391 TI - Developmental Plasticity and Language: A Comparative Perspective. AB - The growing field of evo-devo is increasingly demonstrating the complexity of steps involved in genetic, intracellular regulatory, and extracellular environmental control of the development of phenotypes. A key result of such work is an account for the remarkable plasticity of organismal form in many species based on relatively minor changes in regulation of highly conserved genes and genetic processes. Accounting for behavioral plasticity is of similar potential interest but has received far less attention. Of particular interest is plasticity in communication systems, where human language represents an ultimate target for research. The present paper considers plasticity of language capabilities in a comparative framework, focusing attention on examples of a remarkable fact: Whereas there exist design features of mature human language that have never been observed to occur in non-humans in the wild, many of these features can be developed to notable extents when non-humans are enculturated through human training (especially with intensive social interaction). These examples of enculturated developmental plasticity across extremely diverse taxa suggest, consistent with the evo-devo theme of highly conserved processes in evolution, that human language is founded in part on cognitive capabilities that are indeed ancient and that even modern humans show self-organized emergence of many language capabilities in the context of rich enculturation, built on the special social/ecological history of the hominin line. Human culture can thus be seen as a regulatory system encouraging language development in the context of a cognitive background with many highly conserved features. PMID- 27003390 TI - Behavioral activation for late adolescents with subthreshold depression: a randomized controlled trial. AB - The main behavioral characteristic of subthreshold depression that is observed in adolescents is the low frequency of exposure to environmental rewards. Therefore, it was considered that a simple intervention conducted in short sessions, focusing on increasing access to positively reinforcing activities, would be efficacious in increasing the availability of rewards. We conduct a randomized controlled trial to examine the efficacy of such a behavioral activation program that was conducted weekly for 5 weeks in 60-min sessions. Late adolescent university students aged 18-19 years with subthreshold depression were randomly allocated to a treatment (n = 62) or a control group (n = 56). The primary outcome of the study was the Beck Depression Inventory-II score. Results indicated that late adolescent students in the treatment group showed significant improvements in their depressive symptoms (effect size -0.90, 95 % CI -1.28 to 0.51) compared to the control group. Students in the treatment group also showed significant improvements in self-reported rating of quality of life and in behavioral characteristics. It is concluded that this intervention had a large and significant effect despite being short and simple and that this low-intensity cognitive behavioral therapy program could be conducted in many different types of institutions. It is suggested that the long-term effects of the treatment program should be targeted for investigation in future studies. PMID- 27003392 TI - Effect of Enalapril on Preventing Anthracycline-Induced Cardiomyopathy. AB - Anthracycline (ANT) is a topoisomerase-interacting agent that is used in most malignancy treatments. We investigated the efficacy of enalapril (angiotensin converting enzyme inhibitor) in the prevention of ANT-induced cardiomyopathy. In this randomized, single-blind, and placebo-controlled study, 69 patients with a newly diagnosed malignancy for which ANT therapy was planned were randomly assigned to either a group receiving enalapril (n = 34) or placebo (n = 35). Echocardiography studies were performed before chemotherapy and at 6 months after randomization. Additionally, troponin I and creatinine kinase-MB (CK-MB) were measured 1 month after the initiation of chemotherapy. In the enalapril group, the mean left ventricular ejection fraction (LVEF) (p = 0.58) was the same at baseline and 6 months after randomization. Conversely, LVEF significantly decreased in the control group (p < 0.001). Additionally, LV end systolic volume and left atrial diameter were significantly increased compared with the baseline measures in the control group. According to the tissue Doppler study, the mitral annuli early diastolic (e') and peak systolic (s') velocities were significantly reduced, and the E (the peak early diastolic velocity)/e' ratio was significantly increased in the control group. Furthermore, the TnI and CK-MB levels were significantly higher in the control group than in the enalapril group. Enalapril appears efficacious in preserving systolic and diastolic function in cancer patients treated with ANTs. PMID- 27003393 TI - Novel domino procedures for the synthesis of chromene derivatives and their isomerization. AB - Novel tricyclic keto diesters have been synthesized by a one-pot three-component procedure via DABCO-catalyzed domino Knoevenagel-Michael addition reactions. Also, an efficient four-component reaction for the synthesis of another new group of tricyclic keto diesters has been developed via domino Knoevenagel intramolecular oxo-Diels-Alder reactions. A selective thermal isomerization of the synthesized chromenes to fumarates is also described. X-ray analyses confirm unambiguously the structures of the products. PMID- 27003394 TI - Hepatocyte Growth Factor and Satellite Cell Activation. AB - Satellite cells are the "currency" for the muscle growth that is critical to meat production in many species, as well as to phenotypic distinctions in development at the level of species or taxa, and for human muscle growth, function and regeneration. Careful research on the activation and behaviour of satellite cells, the stem cells in skeletal muscle, including cross-species comparisons, has potential to reveal the mechanisms underlying pathological conditions in animals and humans, and to anticipate implications of development, evolution and environmental change on muscle function and animal performance. PMID- 27003395 TI - Cytokine Mediated Control of Muscle Stem Cell Function. AB - Skeletal muscle stem cells, known as satellite cells (SC), are an absolute requirement for muscle regeneration and contribute significantly to post-natal muscle growth. This stem cell population is governed by a network of transcription factors collectively referred to as the myogenic regulatory factors. These factors are responsible for the progression of a SC from the quiescent state through activation, proliferation and terminal differentiation in a process referred to as the myogenic programme. At each stage in this process, cytokines and growth factors have been shown to play a role in directing the myogenic response. The myogenic programme is complex and requires input from a host of factors that provide both stimulatory and inhibitory signals that regulate SC. Despite years of work in this field, there remains a paucity of information on the precise factors that drive the myogenic programme. In recent years, factors, such as IL-6, have been shown to be critical factors in promoting SC proliferation. In fact, a complete absence of IL-6 in skeletal muscle substantially impairs muscle SC proliferation. These observations highlight the potential importance of the inflammatory response and the cross-talk between inflammatory cells and SC in promoting muscle repair and growth. This chapter will focus on recent advances in cytokine (and some growth factors) regulation of SC. Work from cell, animal and human models will be discussed. PMID- 27003396 TI - The Role of Leukemia Inhibitory Factor Receptor Signaling in Skeletal Muscle Growth, Injury and Disease. AB - Cytokines are an incredibly diverse group of secreted proteins with equally diverse functions. The actions of cytokines are mediated by the unique and sometimes overlapping receptors to which the soluble ligands bind. Classified within the interleukin-6 family of cytokines are leukemia inhibitory factor (LIF), oncostatin-M (OSM), cardiotrophin-1 (CT-1) and ciliary neurotrophic factor (CNTF). These cytokines all bind to the leukemia inhibitory factor receptor (LIFR) and gp130, and in some cases an additional receptor subunit, leading to activation of downstream kinases and transcriptional activators. LIFR is expressed on a broad range of cell types and can generate pleiotropic effects. In the context of skeletal muscle physiology, these cytokines have been shown to exert effects on motor neurons, inflammatory and muscle cells. From isolated cells through to whole organisms, manipulations of LIFR signaling cytokines have a wide range of outcomes influencing muscle cell growth, myogenic differentiation, response to exercise, metabolism, neural innervation and recruitment of inflammatory cells to sites of muscle injury. This article will discuss the shared and distinct processes that LIFR cytokines regulate in a variety of experimental models with the common theme of skeletal muscle physiology. PMID- 27003397 TI - Function of Membrane-Associated Proteoglycans in the Regulation of Satellite Cell Growth. AB - Muscle growth can be divided into embryonic and postnatal periods. During the embryonic period, mesenchymal stem cells proliferate and differentiate to form muscle fibers. Postnatal muscle growth (hypertrophy) is characterized by the enlargement of existing muscle fiber size. Satellite cells (also known as adult myoblasts) are responsible for hypertrophy. The activity of satellite cells can be regulated by their extracellular matrix (ECM). The ECM is composed of collagens, proteoglycans, non-collagenous glycoproteins, cytokines and growth factors. Proteoglycans contain a central core protein with covalently attached glycosaminoglycans (GAGs: chondroitin sulfate, keratan sulfate, dermatan sulfate, and heparan sulfate) and N- or O-linked glycosylation chains. Membrane-associated proteoglycans attach to the cell membrane either through a glycosylphosphatidylinositol anchor or transmembrane domain. The GAGs can bind proteins including cytokines and growth factors. Both cytokines and growth factors play important roles in regulating satellite cell growth and development. Cytokines are generally associated with immune cells. However, cytokines can also affect muscle cell development. For instance, interleukin-6, tumor necrosis factor-alpha, and leukemia inhibitory factor have been reported to affect the proliferation and differentiation of satellite cells and myoblasts. Growth factors are potent stimulators or inhibitors of satellite cell proliferation and differentiation. The proper function of some cytokines and growth factors requires an interaction with the cell membrane-associated proteoglycans to enhance the affinity to bind to their primary receptors to initiate downstream signal transduction. This chapter is focused on the interaction of membrane associated proteoglycans with cytokines and growth factors, and their role in satellite cell growth and development. PMID- 27003398 TI - The TGF-beta Signalling Network in Muscle Development, Adaptation and Disease. AB - Skeletal muscle possesses remarkable ability to change its size and force producing capacity in response to physiological stimuli. Impairment of the cellular processes that govern these attributes also affects muscle mass and function in pathological conditions. Myostatin, a member of the TGF-beta family, has been identified as a key regulator of muscle development, and adaptation in adulthood. In muscle, myostatin binds to its type I (ALK4/5) and type II (ActRIIA/B) receptors to initiate Smad2/3 signalling and the regulation of target genes that co-ordinate the balance between protein synthesis and degradation. Interestingly, evidence is emerging that other TGF-beta proteins act in concert with myostatin to regulate the growth and remodelling of skeletal muscle. Consequently, dysregulation of TGF-beta proteins and their associated signalling components is increasingly being implicated in muscle wasting associated with chronic illness, ageing, and inactivity. The growing understanding of TGF-beta biology in muscle, and its potential to advance the development of therapeutics for muscle-related conditions is reviewed here. PMID- 27003399 TI - Adipokines in Healthy Skeletal Muscle and Metabolic Disease. AB - Adipose tissue not only functions as a reserve to store energy but has become of major interest as an endocrine organ, releasing signalling molecules termed adipokines which impact on other tissues, such as skeletal muscle. Adipocytes, within skeletal muscle and adipose tissue, secrete adipokines to finely maintain the balance between feed intake and energy expenditure. This book chapter focuses on the three adipokines, adiponectin, leptin and IL-6, which have potent effects on skeletal muscle during rest and exercise. Similarly, adiponectin, leptin and IL-6 enhance glucose uptake and increase fatty acid oxidation in skeletal muscle. Fatty acid oxidation is increased through activation of AMPK (adenosine monophosphate-activated protein kinase signalling) causing phosphorylation and inhibition of ACC (acetyl-coenzyme A carboxylase), decreasing availability of malonyl CoA. Leptin and adiponectin also control feed intake via AMPK signalling in the hypothalamus. Adipokines function to maintain energy homeostasis, however, when feed intake exceeds energy expenditure adipokines can become dysregulated causing lipotoxicity in skeletal muscle and metabolic disease can prevail. Cross talk between adipocytes and skeletal muscle via correct control by adipokines is important in controlling energy homeostasis during rest and exercise and can help prevent metabolic disease. PMID- 27003400 TI - Role of Growth Factors in Modulation of the Microvasculature in Adult Skeletal Muscle. AB - Post-natal skeletal muscle is a highly plastic tissue that has the capacity to regenerate rapidly following injury, and to undergo significant modification in tissue mass (i.e. atrophy/hypertrophy) in response to global metabolic changes. These processes are reliant largely on soluble factors that directly modulate muscle regeneration and mass. However, skeletal muscle function also depends on an adequate blood supply. Thus muscle regeneration and changes in muscle mass, particularly hypertrophy, also demand rapid changes in the microvasculature. Recent evidence clearly demonstrates a critical role for soluble growth factors in the tight regulation of angiogenic expansion of the muscle microvasculature. Furthermore, exogenous modulation of these factors has the capacity to impact directly on angiogenesis and thus, indirectly, on muscle regeneration, growth and performance. This chapter reviews recent developments in understanding the role of growth factors in modulating the skeletal muscle microvasculature, and the potential therapeutic applications of exogenous angiogenic and anti-angiogenic mediators in promoting effective growth and regeneration, and ameliorating certain diseases, of skeletal muscle. PMID- 27003402 TI - Macroinvertebrate diversity loss in urban streams from tropical forests. AB - The increase of human activities in recent years has significantly interfered and affected aquatic ecosystems. In this present study, we investigate the effects of urbanization in the community structure of aquatic macroinvertebrates from Atlantic Forest streams. The sampling was conducted in the mountainous region of the State of Rio de Janeiro, Brazil in 10 urban and 10 preserved streams during the dry season (August-September) of 2012. The streams were characterized for its environmental integrity conditions and physico-chemical properties of water. The macroinvertebrates were sampled on rocky substrates with a kicknet. A total of 5370 individuals were collected from all streams and were distributed among Ephemeroptera, Odonata, Plecoptera, Hemiptera, Megaloptera, Coleoptera, Trichoptera, Lepidoptera, and Diptera. In urban sites, all those orders were found, except Megaloptera, while only Mollusca was not found in preserved streams. We performed a non-metric multidimensional scaling (NMDS) analysis that separated two groups distributed among sites in urban communities and another group outside this area. The dominance was significantly higher at urban sites, while the alpha diversity and equitability were greater in preserved sites. A canonical correspondence analysis (CCA) was also performed, indicating that most taxa associated with high values of the Habitat Integrity Index (HII) and a few genus of the order Diptera with the high values of ammonia, total nitrogen, associated to streams in urban sites. Urban and preserved streams differ by physical-chemical variables and aquatic macroinvertebrates. In urban streams, there is most dominance, while alpha diversity and equitability are higher in preserved streams. PMID- 27003401 TI - The mismatch of bioaccumulated trace metals (Cu, Pb and Zn) in field and transplanted oysters (Saccostrea glomerata) to ambient surficial sediments and suspended particulate matter in a highly urbanised estuary (Sydney estuary, Australia). AB - A significant correlation between sedimentary metals, particularly the 'bio available' fraction, and bioaccumulated metal concentrations in the native Sydney rock oyster (Saccostrea glomerata) tissues has been successfully demonstrated previously for Cu and Zn in a number of estuaries in New South Wales, Australia. However, this relationship has been difficult to establish in a highly modified estuary (Sydney estuary, Australia) where metal contamination is of greatest concern and where a significant relationship would be most useful for environmental monitoring. The use of the Sydney rock oyster as a biomonitoring tool for metal contamination was assessed in the present study by investigating relationships between metals attached to sediments and suspended particulate matter (SPM) to bioaccumulated concentrations in oyster tissues. Surficial sediments (both total and fine-fraction), SPM and wild oysters were collected over 3 years from three embayments (Chowder Bay, Mosman Bay and Iron Cove) with each embayment representing a different physiographic region of Sydney estuary. In addition, a transplant experiment of farmed oysters was conducted in the same embayments for 3 months. No relationship was observed between sediments or SPM metals (Cu, Pb and Zn) to tissue of wild oysters; however, significant relationship was observed against transplanted oysters. The mismatch between wild and farmed, transplanted oysters is perplexing and indicates that wild oysters are unsuitable to be used as a biomonitoring tool due to the involvement of unknown complex factors while transplanted oysters hold strong potential. PMID- 27003403 TI - Development of a new method for sampling and monitoring oncology staff exposed to cyclophosphamide drug. AB - Treatment using cytotoxic drugs is considered to be the most common treatment for cancers. However, the widespread use of these drugs on the health status of the staff at the oncology department has become a great concern. Due to challenges of sampling and analysis of cytotoxic drugs, the aim of this study was to development a novel practical method called Needle trap devices (NTD) for sampling and analysis of personal exposure to cyclophosphamide drug. The sampler consisted of a stainless steel hyper needle gauge 21 of length 9 cm packed with Carboxen 1000 for adsorbing cyclophosphamide. A total of 41 samples of staff's air breathing zone in different wards of the oncology department were taken with the sampler. Samples were analyzed by gas chromatography coupled with electron capture detector (ECD). Linear range concentration was 212-1062 MUg/m(3), and LOD and LOQ were 100 and 191 MUg/m(3), respectively. The mean inter-day and intra-day coefficient variations for standards within linear range concentration were 8.9 and 4.8 %, respectively. Detectable levels of cyclophosphamide were measured in 31.7 % of air samples. The developed method is user-friendly, quick, and precise for sampling of airborne cyclophosphamide. The results showed that some staff of the oncology department were exposed to the carcinogenic drug and their health were at risk. Since carcinogens do not have a threshold and oncology staffs with their continuous exposure might be at risk, therefore, proper work practice and adequate control measures are essential to ensure their wellbeing. PMID- 27003404 TI - Anopheles (Anopheles) petragnani Del Vecchio 1939-a new mosquito species for Germany. AB - The so far known species of the Anopheles Claviger Complex, Anopheles claviger s.s. and Anopheles petragnani, can only be distinguished by partial overlapping characteristics of immature stages and by nucleotide sequence variation of the genomic ribosomal DNA (rDNA) internal transcribed spacer 2 (ITS2) region. The known distribution of An. petragnani is so far restricted to the western Mediterranean region, whereas An. claviger s.s. occurs across most of Europe, up to the Middle East and North Africa. In our study, we investigated the larval mosquito fauna in rock pools of the Murg valley (Black Forest, Germany) once a month from April to December 2015.Among other species, larvae belonging to the Anopheles Claviger Complex were found. The fourth instar larvae were morphologically identified by chaetotaxy of the head and abdomen. The results were confirmed by a multiplex PCR and additional sequencing of the amplificates.Of the 1289 collected larvae from the rock pools, seven belonged to the Anopheles Claviger Complex. Five individuals were determined morphologically as An. petragnani and two as An. claviger s.s. The associated mosquito fauna comprised of Aedes japonicus japonicus (548 individuals), Culex pipiens s.l. and Culex torrentium (493 individuals) and Culex hortensis (241 individuals).This is the first record of An. petragnani north of the Alps. Further studies will reveal whether this is an isolated population of An. petragnani and if the investigated rock pool breeding sites represent typical habitats of this species in temperate regions in Central Europe. PMID- 27003405 TI - Evaluation of medicated feeds with antiparasitical and immune-enhanced Chinese herbal medicines against Ichthyophthirius multifiliis in grass carp (Ctenopharyngodon idellus). AB - Since malachite green was banned for using in food fish due to its carcinogenic and teratogenic effects on human, the search of alternative drug to treat Ichthyophthirius multifiliis becomes urgent. This study aimed to (1) evaluate the ethanol extracts of medicinal plants Cynanchum atratum, Zingiber officinale, Cynanchum paniculatum, immunostimulant (A), and immunostimulant (B) for their efficacy against I. multifiliis, and (2) determine effects of medicated feeds with C. atratum, Z. officinale, C. paniculatum, and immunostimulant (A) to treat I. multifiliis in grass carp. The results in this study showed that the minimum concentrations of C. atratum, Z. officinale, and C. paniculatum extracts for killing all theronts were 16, 8, and 16 mg/L, respectively. In vivo experiments, fish fed with medicated feeds of C. atratum for 10 days, or Z. officinale for 3 days, or combination of three plants for 10 days resulted in a significant reduction in the I. multifiliis infective intensity on grass carp after theronts exposure. Grass carp fed with medicated feeds of immunostimulant (A) for 21 days showed no infection and 100 % of survival 15 days post theronts exposure. Therefore, immunostimulant (A) is a promising feed supplement to treated I. multifiliis with good antiparasitic efficacy. PMID- 27003406 TI - Identification of Hepatozoon erhardovae Krampitz, 1964 from bank voles (Myodes glareolus) and fleas in Southern Hungary. AB - In order to investigate the prevalence and life cycle of apicomplexan parasites, small mammals were live-trapped with modified Sherman traps in Southern Hungary between 2010 and 2012. Altogether, 528 rodents (Apodemus flavicollis Melchior, 1834, Apodemus agrarius Pallas, 1771, Myodes glareolus Schreber, 1780, Microtus agrestis Linnaeus, 1761, Mus musculus Linnaeus, 1758 and Micromys minutus Pallas, 1771) were collected and four shrews (Sorex spp.) were by-catched. Captured animals belonging to non-protected species were euthanized, and spleen samples were preserved for histological and molecular analyses. During the examination of spleen smears, Hepatozoon parasites were observed in eight out of 48 bank voles (M. glareolus). DNA was isolated from altogether 221 spleen samples, and 18S rDNA was amplified using two different PCR protocols. The eight bank vole samples were positive with PCR, but none of the other M. glareolus spleen samples or any of the tissue samples from other species were found to be infected. Sequenced amplicons were very similar to Hepatozoon spp. detected in M. glareolus in Spain and Poland. Ectoparasites were collected from the small mammal carcasses and from the vegetation. Hepatozoon DNA was not found in the 181 ticks removed from the small mammals or in the 162 ticks collected with flagging, but was detected in all three flea species (4/43 Megabothris turbidus Rothschild, 1909, 3/10 Ctenophthalmus assimilis Taschenberg, 1880 and 7/78 Ctenophthalmus agyrtes Heller, 1896). Based on gamont morphology, vertebrate and arthropod host species and DNA sequences, the parasites in our study can be identified as Hepatozoon erhardovae. PMID- 27003407 TI - The Preferred Directions of Conjunctive Grid X Head Direction Cells in the Medial Entorhinal Cortex Are Periodically Organized. AB - The discovery of speed-modulated grid, head direction, and conjunctive grid x head direction cells in the medial entorhinal cortex has led to the hypothesis that path integration, the updating of one's spatial representation based on movement, may be carried out within this region. This hypothesis has been formalized by many computational models, including a class known as attractor network models. While many of these models propose specific mechanisms by which path integration might occur, predictions of these specific mechanisms have not been tested. Here I derive and test a key prediction of one attractor network path integration mechanism. Specifically, I first demonstrate that this mechanism predicts a periodic distribution of conjunctive cell preferred directions in order to minimize drift. Next, I test whether conjunctive cell preferred directions are in fact periodically organized. Results indicate that conjunctive cells are preferentially tuned to increments of 36 degrees , consistent with drift minimization in this path integration mechanism. By contrast, no periodicity was observed in the preferred directions of either pure grid or pure head direction cells. These results provide the first neural evidence of a nonuniform structure in the directional preferences of any head direction representation found in the brain. PMID- 27003408 TI - Assessment of Glial Scar, Tissue Sparing, Behavioral Recovery and Axonal Regeneration following Acute Transplantation of Genetically Modified Human Umbilical Cord Blood Cells in a Rat Model of Spinal Cord Contusion. AB - OBJECTIVE AND METHODS: This study investigated the potential for protective effects of human umbilical cord blood mononuclear cells (UCB-MCs) genetically modified with the VEGF and GNDF genes on contusion spinal cord injury (SCI) in rats. An adenoviral vector was constructed for targeted delivery of VEGF and GDNF to UCB-MCs. Using a rat contusion SCI model we examined the efficacy of the construct on tissue sparing, glial scar severity, the extent of axonal regeneration, recovery of motor function, and analyzed the expression of the recombinant genes VEGF and GNDF in vitro and in vivo. RESULTS: Transplantation of UCB-MCs transduced with adenoviral vectors expressing VEGF and GDNF at the site of SCI induced tissue sparing, behavioral recovery and axonal regeneration comparing to the other constructs tested. The adenovirus encoding VEGF and GDNF for transduction of UCB-MCs was shown to be an effective and stable vehicle for these cells in vivo following the transplantation into the contused spinal cord. CONCLUSION: Our results show that a gene delivery using UCB-MCs-expressing VEGF and GNDF genes improved both structural and functional parameters after SCI. Further histological and behavioral studies, especially at later time points, in animals with SCI after transplantation of genetically modified UCB-MCs (overexpressing VEGF and GDNF genes) will provide additional insight into therapeutic potential of such cells. PMID- 27003409 TI - A Large Proportion of the Mexican Population Remained Susceptible to A(H1N1)pdm09 Infection One Year after the Emergence of 2009 Influenza Pandemic. AB - BACKGROUND: The 2009 H1N1 influenza pandemic initially affected Mexico from April 2009 to July 2010. By August 2010, a fourth of the population had received the monovalent vaccine against the pandemic virus (A(H1N1)pdm09). To assess the proportion of the Mexican population who remained potentially susceptible to infection throughout the summer of 2010, we estimated the population seroprevalence to A(H1N1)pdm09 in a serosurvey of blood donors. METHODS: We evaluated baseline cross-reactivity to the pandemic strain and set the threshold for seropositivity using pre-pandemic (2005-2008) stored serum samples and sera from confirmed A(H1N1)pdm09 infected individuals. Between June and September 2010, a convenience sample serosurvey of adult blood donors, children, and adolescents was conducted in six states of Mexico. Sera were tested by the microneutralization (MN) and hemagglutination inhibition (HI) assays, and regarded seropositive if antibody titers were equal or exceeded 1:40 for MN and 1:20 for HI. Age-standardized seroprevalence were calculated using the 2010 National Census population. RESULTS: Sera from 1,484 individuals were analyzed; 1,363 (92%) were blood donors, and 121 (8%) children or adolescents aged <=19 years. Mean age (standard deviation) was 31.4 (11.5) years, and 276 (19%) were women. A total of 516 (35%) participants declared history of influenza vaccination after April 2009. The age-standardized seroprevalence to A(H1N1)pdm09 was 48% by the MN and 41% by the HI assays, respectively. The youngest quintile, aged 1 to 22 years, had the highest the seroprevalence; 61% (95% confidence interval [CI]: 56, 66%) for MN, and 56% (95% CI: 51, 62%) for HI. CONCLUSIONS: Despite high transmission of A(H1N1)pdm09 observed immediately after its emergence and extensive vaccination, over a half of the Mexican population remained potentially susceptible to A(H1N1)pdm09 infection. Subsequent influenza seasons with high transmission of A(H1N1)pdm09, as 2011-2012 and 2013-2014, are compatible with these findings. PMID- 27003410 TI - Background Speech Effects on Sentence Processing during Reading: An Eye Movement Study. AB - Effects of background speech on reading were examined by playing aloud different types of background speech, while participants read long, syntactically complex and less complex sentences embedded in text. Readers' eye movement patterns were used to study online sentence comprehension. Effects of background speech were primarily seen in rereading time. In Experiment 1, foreign-language background speech did not disrupt sentence processing. Experiment 2 demonstrated robust disruption in reading as a result of semantically and syntactically anomalous scrambled background speech preserving normal sentence-like intonation. Scrambled speech that was constructed from the text to-be read did not disrupt reading more than scrambled speech constructed from a different, semantically unrelated text. Experiment 3 showed that scrambled speech exacerbated the syntactic complexity effect more than coherent background speech, which also interfered with reading. Experiment 4 demonstrated that both semantically and syntactically anomalous speech produced no more disruption in reading than semantically anomalous but syntactically correct background speech. The pattern of results is best explained by a semantic account that stresses the importance of similarity in semantic processing, but not similarity in semantic content, between the reading task and background speech. PMID- 27003412 TI - Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine Pancreas. AB - Endoscopic ultrasound (EUS) imaging of adrenal glands and its application to diagnostic procedures of adrenal diseases has been reported since 1998. It can be considered a relevant advantage in the field of adrenal diseases. Indeed, EUS allows the detection of adrenal lesions (even very small ones) and their characterization, the assessment of malignancy criteria, the early detection of neoplastic recurrences, the preoperative identification of morphologically healthy parts of the glands, the differentiation of extra-adrenal from adrenal tumors, and of the pathological entities associated with adrenal insufficiency, and the fine-needle aspiration biopsy (EUS-FNA) of suspicious lesions. At the same time, its clinical relevance depends on the experience of the endosonographer. Moreover, EUS is also by far the best and most sensitive imaging technique to detect and assess the follow-up of pancreatic manifestation of MEN1 disease. It furthermore enables the preoperatively localization of insulinomas and critical structures in their neighborhood, and may be relevant in planning surgical strategy. A positive EUS in a case of insulinoma furthermore confirms the endocrine diagnosis, especially considering the differential diagnosis of hypoglycemia factitia by oral antidiabetics. It can be supplemented by EUS-FNA. Again, it has to be considered that EUS may reveal false positive and false negative results, and the quality of the findings largely depends on the endosonographer's skills and experience. The most important technical details together with the advantages and limitations of EUS, and the pathognomonic characteristic of benign and malignant disorders of the adrenals and pancreas are presented here. PMID- 27003411 TI - Juvenile Hormone Is Required in Adult Males for Drosophila Courtship. AB - Juvenile Hormone (JH) has a prominent role in the regulation of insect development. Much less is known about its roles in adults, although functions in reproductive maturation have been described. In adult females, JH has been shown to regulate egg maturation and mating. To examine a role for JH in male reproductive behavior we created males with reduced levels of Juvenile Hormone Acid O-Methyl Transferase (JHAMT) and tested them for courtship. JHAMT regulates the last step of JH biosynthesis in the Corpora Allata (CA), the organ of JH synthesis. Males with reduced levels of JHAMT showed a reduction in courtship that could be rescued by application of Methoprene, a JH analog, shortly before the courtship assays were performed. In agreement with this, reducing JHAMT conditionally in mature flies led to courtship defects that were rescuable by Methoprene. The same result was also observed when the CA were conditionally ablated by the expression of a cellular toxin. Our findings demonstrate that JH plays an important physiological role in the regulation of male mating behavior. PMID- 27003413 TI - [Pancreatic neuroendocrine neoplasms]. AB - Pancreatic neuroendocrine neoplasms (NEN) account for 1-2% of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. PMID- 27003414 TI - Cytokines of Cervical Mucosa and Human Papilloma Virus Infection of the Cervix: A Descriptive Study. AB - OBJECTIVE: The production of cytokines by various cervical cells can be triggered by antigenic stimuli, including human papilloma virus (HPV) infection. The aim of the present study was to evaluate differences in cytokine levels between various intraepithelial cervical lesions. STUDY DESIGN: A total of 97 women participated in this descriptive study. Within our study population, 27 subjects presented with high-grade squamous intraepithelial lesions (HSIL), 48 with low-grade squamous intraepithelial lesion (LSIL) and 22 with a normal smear. Colposcopy and directed biopsy were performed as needed. To confirm the presence of HPV, an HPV DNA test was performed using polymerase chain reaction. Using flow cytometry to ThinPrep cervical samples, we assessed the family of interleukins (ILs), including IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF)-alpha and TNF-beta and transforming growth factor-beta1. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS for Windows; version 20.0). RESULTS: Significantly lower levels of IL-1alpha, IL-2, IL-4 and TNF-alpha were detected in cervical samples obtained from the LSIL group when compared to samples obtained from the HSIL group. CONCLUSION: Significant differences in tissue cytokine levels exist between intraepithelial cervical lesions obtained from patients presenting with HSIL versus LSIL. PMID- 27003415 TI - Application of Rigidity Theory to the Thermostabilization of Lipase A from Bacillus subtilis. AB - Protein thermostability is a crucial factor for biotechnological enzyme applications. Protein engineering studies aimed at improving thermostability have successfully applied both directed evolution and rational design. However, for rational approaches, the major challenge remains the prediction of mutation sites and optimal amino acid substitutions. Recently, we showed that such mutation sites can be identified as structural weak spots by rigidity theory-based thermal unfolding simulations of proteins. Here, we describe and validate a unique, ensemble-based, yet highly efficient strategy to predict optimal amino acid substitutions at structural weak spots for improving a protein's thermostability. For this, we exploit the fact that in the majority of cases an increased structural rigidity of the folded state has been found as the cause for thermostability. When applied prospectively to lipase A from Bacillus subtilis, we achieved both a high success rate (25% over all experimentally tested mutations, which raises to 60% if small-to-large residue mutations and mutations in the active site are excluded) in predicting significantly thermostabilized lipase variants and a remarkably large increase in those variants' thermostability (up to 6.6 degrees C) based on single amino acid mutations. When considering negative controls in addition and evaluating the performance of our approach as a binary classifier, the accuracy is 63% and increases to 83% if small-to-large residue mutations and mutations in the active site are excluded. The gain in precision (predictive value for increased thermostability) over random classification is 1.6-fold (2.4-fold). Furthermore, an increase in thermostability predicted by our approach significantly points to increased experimental thermostability (p < 0.05). These results suggest that our strategy is a valuable complement to existing methods for rational protein design aimed at improving thermostability. PMID- 27003416 TI - Glycogen Synthase Kinase-3beta: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals. AB - Evidence indicates a role for glycogen synthase kinase-3beta (GSK-3beta) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3beta activity over time is unknown. We aimed to investigate GSK-3beta activity over time and its possible correlation with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3beta and serine-9-phosphorylated GSK-3beta in peripheral blood mononuclear cells were quantitated using enzyme immunometric assays. The activity of GSK-3beta (serine-9-phosphorylated GSK-3beta/total GSK-3beta) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3beta and serine-9-phosphorylated GSK-3beta. Exploratory analysis revealed lower activity of GSK-3beta in spring and summer compared with the fall season. No correlation was observed between GSK-3beta activity and emotional lability, subjective mood fluctuations or cognitive function. The results suggest that intra- and interindividual variation in GSK 3beta activity over time could contribute to the heterogeneity of findings in clinical studies. The stability of GSK-3beta activity and the role of potential moderators of GSK-3beta activity warrant further investigation. Clinical studies of GSK-3beta should consider including repeated measures of both cases and healthy individuals. PMID- 27003417 TI - Imaging characteristic of dual-phase (18)F-florbetapir (AV-45/Amyvid) PET for the concomitant detection of perfusion deficits and beta-amyloid deposition in Alzheimer's disease and mild cognitive impairment. AB - PURPOSE: We investigated dual-phase (18)F-florbetapir (AV-45/Amyvid) PET imaging for the concomitant detection of brain perfusion deficits and beta-amyloid deposition in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), and in cognitively healthy controls (HCs). METHODS: A total of 82 subjects (24 AD patients, 44 MCI patients and 14 HCs) underwent both dual phase (18)F-AV-45 PET and MRI imaging. Dual-phase dynamic PET imaging consisted of (1) five 1-min scans obtained 1 - 6 min after tracer injection (perfusion (18)F-AV-45 imaging, pAV-45), and (2) ten 1-min scans obtained 50 - 60 min after tracer injection (amyloid (18)F-AV-45 imaging). Amyloid-negative MCI/AD patients were excluded. Volume of interest analysis and statistical parametric mapping of pAV-45 and (18)F-AV-45 images were performed to investigate the perfusion deficits and the beta-amyloid burden in the three study groups. The associations between Mini-Mental State Examination (MMSE) scores and global perfusion deficits and amyloid deposition were investigated with linear and segmental linear correlation analyses. RESULTS: HCs generally had normal pAV-45 findings, whereas perfusion deficits were evident in the hippocampus, and temporal, parietal and middle frontal cortices in both MCI and AD patients. The motor-sensory cortex was relatively preserved. MMSE scores in the entire study cohort were significantly associated with the degree of perfusion impairment as assessed by pAV-45 imaging (r = 0.5156, P < 0.0001). (18)F-AV-45 uptake was significantly higher in AD patients than in the two other study groups. However, the correlation between MMSE scores and (18)F-AV-45 uptake in MCI patients was more of a binary phenomenon and began in MCI patients with MMSE score 23.14 when (18)F-AV-45 uptake was higher and MMSE score lower than in patients with early MCI. Amyloid deposition started in the precuneus and the frontal and temporal regions in early MCI, ultimately reaching the maximum burden in advanced MCI. CONCLUSION: Our results indicate that brain perfusion deficits and beta-amyloid deposition in AD follow different trajectories that can be successfully traced using dual-phase (18)F-AV-45 PET imaging. PMID- 27003419 TI - Adolescent autonomy revisited: clinicians need clearer guidance. AB - In 1996, Brazier and Bridge raised the question 'is adolescent autonomy truly dead and buried' following judicial decisions which had seemed to reverse the Gillick-inspired trend for greater child autonomy in healthcare. Subsequent decisions by the courts have reinforced the view that those below 18 years in England and Wales remain children with limited rights to refuse treatment compared with adults. This is at variance with the daily experience of those working with young people who increasingly seek to actively involve them in making freely informed decisions about their healthcare, in accordance with the principles enunciated in the UN Convention of the Rights of the Child and the UK Children Acts. We review the derivation of the law in England and Wales in this area, in the light of another recent family court judgement enforcing treatment on a 'competent' child without his or her consent and ask: 'How can the Common Law and the ethical practice of those caring for young people have diverged so far?' Either young people can decide whether to have a recommended treatment, or they cannot. Given Ian McEwan's book, the Children Act, has stimulated wider social debate in this area might this be an opportune moment to seek public policy resolution with regards to healthcare decision making by young people? We argue that events since the Gillick case have underlined the need for a comprehensive review of legal policy and practice in this area. While absolute autonomy and freedom of choice are arguably inconsistent with the protection rights that society has agreed are owed to children, healthcare practitioners need clarity over the circumstances in which society expects that autonomous choices of adolescents can be overridden. PMID- 27003418 TI - D-Serine and Glycine Differentially Control Neurotransmission during Visual Cortex Critical Period. AB - N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity. Their activation requires the binding of both glutamate and d-serine or glycine as co-agonist. The prevalence of either co-agonist on NMDA-receptor function differs between brain regions and remains undetermined in the visual cortex (VC) at the critical period of postnatal development. Here, we therefore investigated the regulatory role that d-serine and/or glycine may exert on NMDARs function and on synaptic plasticity in the rat VC layer 5 pyramidal neurons of young rats. Using selective enzymatic depletion of d-serine or glycine, we demonstrate that d-serine and not glycine is the endogenous co-agonist of synaptic NMDARs required for the induction and expression of Long Term Potentiation (LTP) at both excitatory and inhibitory synapses. Glycine on the other hand is not involved in synaptic efficacy per se but regulates excitatory and inhibitory neurotransmission by activating strychnine-sensitive glycine receptors, then producing a shunting inhibition that controls neuronal gain and results in a depression of synaptic inputs at the somatic level after dendritic integration. In conclusion, we describe for the first time that in the VC both D serine and glycine differentially regulate somatic depolarization through the activation of distinct synaptic and extrasynaptic receptors. PMID- 27003420 TI - Unit 731 and moral repair. AB - Unit 731, a biological warfare research organisation that operated under the authority of the Imperial Japanese Army in the 1930s and 1940s, conducted brutal experiments on thousands of unconsenting subjects. Because of the US interest in the data from these experiments, the perpetrators were not prosecuted and the atrocities are still relatively undiscussed. What counts as meaningful moral repair in this case-what should perpetrators and collaborator communities do decades later? We argue for three non-ideal but realistic forms of moral repair: (1) a national policy in Japan against human experimentation without appropriate informed and voluntary consent; (2) the establishment of a memorial to the victims of Unit 731; and (3) US disclosure about its use of Unit 731 data and an apology for failing to hold the perpetrators accountable. PMID- 27003421 TI - Tobacco bans and smokers' autonomy. PMID- 27003422 TI - Thermal tolerance and survival responses to scenarios of experimental climatic change: changing thermal variability reduces the heat and cold tolerance in a fly. AB - Climate change poses one of the greatest threats to biodiversity. Most analyses of the impacts have focused on changes in mean temperature, but increasing variance will also impact organisms and populations. We assessed the combined effects of the mean and the variance of temperature on thermal tolerances-i.e., critical thermal maxima, critical thermal minima, scope of thermal tolerance, and survival in Drosophila melanogaster. Our six experimental climatic scenarios were: constant mean with zero variance or constant variance or increasing variance; changing mean with zero variance or constant variance or increasing variance. Our key result was that environments with changing thermal variance reduce the scope of thermal tolerance and survival. Heat tolerance seems to be conserved, but cold tolerance decreases significantly with mean low as well as changing environmental temperatures. Flies acclimated to scenarios of changing variance-with either constant or changing mean temperatures-exhibited significantly lower survival rate. Our results imply that changing and constant variances would be just as important in future scenarios of climate change under greenhouse warming as increases in mean annual temperature. To develop more realistic predictions about the biological impacts of climate change, such interactions between the mean and variance of environmental temperature should be considered. PMID- 27003423 TI - The 12-day thermoregulatory metamorphosis of Red-winged Blackbirds (Agelaius phoeniceus). AB - We examined development of endothermy in altricial Red-winged Blackbirds (Agelaius phoeniceus) by measuring oxygen consumption [Formula: see text], body temperature and ventilation at ambient temperatures from 35 to 15 degrees C. Mitochondrial respiration of permeabilized skeletal muscle was also measured from breast (pectoralis) and thigh (femorotibialis) muscles. Animals were studied from the first day of hatching through fledging (12 days post-hatch, dph). Nestling whole-body metabolic rate began to show an endothermic response to cold temperature midway between hatching and fledging. Nestlings less than 5 dph were unable to maintain elevated [Formula: see text] and body temperature when exposed to gradually decreasing temperature, whereas 7 dph nestlings maintained [Formula: see text] until ~25 degrees C, after which [Formula: see text] decreased. From 10 dph to fledging, animals maintained elevated [Formula: see text] and body temperature when exposed to gradual cooling; full endothermic capacity was achieved. Ventilation followed a similar developmental trend to that of [Formula: see text], with increases in 10 dph fledglings occurring in tidal volume rather than ventilation frequency. LEAK respiration and oxidative phosphorylation (OXPHOS) through complex I of breast muscle mitochondria increased significantly after 3 dph. Expression of avUCP and PCG-1alpha mRNA increased significantly at 3 dph and remained elevated in both skeletal muscle types. Increased metabolic capacity at the cellular level occurred prior to that of the whole animal. This change in whole animal metabolic capacity increased steadily upon hatching as evidenced by the shift of metabolic rate from an ectothermic to endothermic phenotype and the increase of mitochondrial OXPHOS activity of the shivering muscles of this altricial avian species. PMID- 27003424 TI - The Expression of Nuclear Transcription Factor Kappa B (NF-kappaB) in the Case of Critically Ill Polytrauma Patients with Sepsis and Its Interactions with microRNAs. AB - Critical polytrauma patients present a series of pathophysiological disturbances, biochemical and molecular dysfunction, which comprise to be the major cause of intensive care unit admission. In regard to molecular damage, there exists a series of factors, which all together contribute to the aggravation of the clinical status leading to increased mortality rate in these patients. One of the most important biochemical factors involved is the nuclear transcription factor B (NF-kappaB). Impaired NF-kappaB functioning is reflected on the clinical status of the patient through increased production of pro-inflammatory molecule, leading to multiple organ dysfunction syndrome. In addition to this, through microRNAs interactions, various pathophysiological as well as biochemical disturbances are produced, which altogether further reduce the patient's survival rate. In this paper, we would like to present the modifications seen in the expression of NF kappaB in critically polytraumatized patients with sepsis. In additions to this, we would like to discuss the correlation between the microRNAs and its further implications in clinical status of these patients. PMID- 27003425 TI - Inflammatory and Immune Response Genes Polymorphisms are Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Tatars Population from Russia. AB - Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system affecting primarily distal respiratory pathways and lung parenchyma. This work was designed as a case-control study aimed at investigating the association of COPD with polymorphisms in inflammatory and immune response genes (JAK1, JAK3, STAT1, STAT3, NFKB1, IL17A, ADIPOQ, ADIPOR1, etc.) in Tatar population from Russia. Ten SNPs (rs310216, rs3212780, rs12693591, rs2293152, rs28362491, rs4711998, rs1974226, rs1501299, rs266729, and rs12733285) were genotyped by the real-time polymerase chain reaction (TaqMan assays) in a case-control study (425 COPD patients and 457 in the control group, from Ufa, Russia). Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and pack-years. In Tatar population, significant associations of JAK1 (rs310216) (P = 0.0002, OR 1.70 in additive model), JAK3 (rs3212780) (P = 0.001, OR 1.61 in dominant model), and IL17A (rs1974226) (P = 0.0037, OR 2.31 in recessive model) with COPD were revealed. The disease risk was higher in carriers of insertion allele of NFKB1 (rs28362491) (P = 0.045, OR 1.22). We found a significant gene-by-environment interaction of smoking status and IL17A (rs1974226) (P interact = 0.016), JAK3 (rs3212780) (P interact = 0.031), ADIPOQ (rs266729) (P interact = 0.013), and ADIPOR1 (rs12733285) (P interact = 0.018). The relationship between the rs4711998, rs1974226, rs310216, rs3212780, rs28362491, and smoking pack-years was found (P = 0.045, P = 0.004, P = 0.0005, P = 0.021, and P = 0.042). A significant genotype-dependent variation of forced vital capacity was observed for NFKB1 (rs28362491) (P = 0.017), ADIPOR1 (rs12733285) (P = 0.043), and STAT1 (rs12693591) (P = 0.048). The genotypes of STAT1 (rs12693591) (P = 0.013) and JAK1 (rs310216) (P = 0.048) were associated with forced expiratory volume in 1 s. PMID- 27003426 TI - Hyperoxia toxicity after cardiac arrest: What is the evidence? AB - This review gives an overview of current knowledge on hyperoxia pathophysiology and examines experimental and human evidence of hyperoxia effects after cardiac arrest. Oxygen plays a pivotal role in critical care management as a lifesaving therapy through the compensation of the imbalance between oxygen requirements and supply. However, growing evidence sustains the hypothesis of reactive oxygen species overproduction-mediated toxicity during hyperoxia, thus exacerbating organ failure by various oxidative cellular injuries. In the cardiac arrest context, evidence of hyperoxia effects on outcome is fairly conflicting. Although prospective data are lacking, retrospective studies and meta-analysis suggest that hyperoxia could be associated with an increased mortality. However, data originate from retrospective, heterogeneous and inconsistent studies presenting various biases that are detailed in this review. Therefore, after an original and detailed analysis of all experimental and clinical studies, we herein provide new ideas and concepts that could participate to improve knowledge on oxygen toxicity and help in developing further prospective controlled randomized trials on this topic. Up to now, the strategy recommended by international guidelines on cardiac arrest (i.e., targeting an oxyhemoglobin saturation of 94-98 %) should be applied in order to avoid deleterious hypoxia and potent hyperoxia. PMID- 27003427 TI - Dropwise Evaporative Cooling of Heated Surfaces with Various Wettability Characteristics Obtained by Nanostructure Modifications. AB - A numerical and experimental investigation was conducted to analyze dropwise evaporative cooling of heated surfaces with various wettability characteristics. The surface wettability was tuned by nanostructure modifications. Spray-cooling experiments on these surfaces show that surfaces with better wettability have better heat transfer rate and higher critical heat flux (CHF). Single droplet impingement evaporative cooling of a heated surface was then investigated numerically with various wettability conditions to characterize the effect of contact angle on spray-cooling heat transfer. The volume of fluid (VOF) model with variable-time stepping was used to capture the time-dependent liquid-gas interface motion throughout the computational domain with the kinetic theory model used to predict the evaporation rate at the liquid-gas interface. The numerical results agree with the spray-cooling experiments that dropwise evaporative cooling is much better on surfaces with better wettability because of the better liquid spreading and convection, better liquid-solid contact, and stronger liquid evaporation. PMID- 27003428 TI - Improved Efficiency of Silicon Nanoholes/Gold Nanoparticles/Organic Hybrid Solar Cells via Localized Surface Plasmon Resonance. AB - Silicon is the most widely used material for solar cells due to its abundance, non-toxicity, reliability, and mature fabrication process. In this paper, we fabricated silicon nanoholes (SiNHS)/gold nanoparticles (AuNPS)/organic hybrid solar cells and investigated their spectral and opto-electron conversion properties. SiNHS nanocomposite films were fabricated by metal-assisted electroless etching (EE) method. Then, we modified the surface of the nanocomposite films by exposing the samples in the air. After that, polymer poly(3,4-ethylenedioxythiophene):poly (styrenesulfonate) ( PEDOT: PSS) blended with AuNPS were spin-coated on the surface of the SiNHS nanocomposite films as a hole-transporting layer. The external quantum efficiency (EQE) values of the solar cells with AuNPS are higher than that of the samples without AuNPS in the spectral region of 600-1000 nm, which were essential to achieve high performance photovoltaic cells. The power conversion efficiency (PCE) of the solar cells incorporating AuNPS exhibited an enhancement of 27 %, compared with that of the solar cells without AuNPS. We thought that the improved efficiency were attributed to localized surface plasmon resonance (LSPR) triggered by gold nanoparticles in SiNHS nanocomposite films. PMID- 27003429 TI - Magnetic Nanocomposites as Efficient Sorption Materials for Removing Dyes from Aqueous Solutions. AB - Magnetic composite sorbents based on saponite clays with different content of magnetite (2-7 wt%.) were synthesized. The samples were analyzed by X-ray diffraction methods, and it was found that the Fe3O4 in composites is in the nanorange. It has been shown that the magnetic nanocomposites have more developed microporosity and mesoporosity compared to saponite clay. The sorption properties of magnetic nanocomposite sorbents were determined, and the results evidenced that their efficiency is significantly higher than the individual phases of the composite. It was shown that all waste composite magnetic sorbents are successfully removed from the water environment by magnetic separation. PMID- 27003430 TI - Mechanical circulatory support for patients with peripartum cardiomyopathy. AB - Peripartum cardiomyopathy (PPCM) challenges different disciplines including gynecologists, cardiologists and cardiac surgeons. It is a severe cardiac failure occurring at the end of pregnancy or within the first months after delivery. Urgent intervention is necessary to stabilize hemodynamics with appropriate medication and mechanical assist support. Data of 4 patients with PPCM at a mean age of 28.2 years were analyzed retrospectively. Echocardiography was used to evaluate cardiac function. Despite varying courses of PPCM all women received left ventricular assist devices (LVAD) since their hemodynamics could not be stabilized by medical treatment. Mean gestational week at delivery was 31.5 +/- 4.9. Left ventricular ejection fractions of all patients were severely impaired (17.8 +/- 3.5 %) before LVAD implantations. After long-term mechanical support (282 and 417 days, respectively) 2 patients were successfully transplanted. Two other females could be weaned from LVAD therapy after 944 and 612 days, respectively. LVAD explanations were performed according to a standardized weaning protocol. Myocardial recovery was confirmed by regular echocardiography, spiroergometry and right heart catheterization. Mechanical assist device support is a surgical strategy either as bridge to transplantation or as bridge to recovery for patients with PPCM. PMID- 27003431 TI - Development of in vivo tissue-engineered microvascular grafts with an ultra small diameter of 0.6 mm (MicroBiotubes): acute phase evaluation by optical coherence tomography and magnetic resonance angiography. AB - Biotubes, i.e., in vivo tissue-engineered connective tubular tissues, are known to be effective as vascular replacement grafts with a diameter greater than several millimeters. However, the performance of biotubes with smaller diameters is less clear. In this study, MicroBiotubes with diameters <1 mm were prepared, and their patency was evaluated noninvasively by optical coherence tomography (OCT) and magnetic resonance angiography (MRA). MicroBiotube molds, containing seven stainless wires (diameter 0.5 mm) covered with silicone tubes (outer diameter 0.6 mm) per mold, were embedded into the dorsal subcutaneous pouches of rats. After 2 months, the molds were harvested with the surrounding capsular tissues to obtain seven MicroBiotubes (internal diameter 0.59 +/- 0.015 mm, burst pressure 4190 +/- 1117 mmHg). Ten-mm-long MicroBiotubes were allogenically implanted into the femoral arteries of rats by end-to-end anastomosis. Cross sectional OCT imaging demonstrated the patency of the MicroBiotubes immediately after implantation. In a 1-month follow-up MRA, high patency (83.3 %, n = 6) was observed without stenosis, aneurysmal dilation, or elongation. Native-like vascular structure was reconstructed with completely endothelialized luminal surfaces, mesh-like elastin fiber networks, regular circumferential orientation of collagen fibers, and alpha-SMA-positive cells. Although the long-term patency of MicroBiotubes still needs to be confirmed, they may be useful as an alternative ultra-small-caliber vascular substitute. PMID- 27003432 TI - Safe ECMO femoral decannulation by placement of inferior vena cava filter via internal jugular vein. AB - Veno-arterial extracorporeal membrane oxygenation (ECMO) is a lifesaving treatment in patients with cardiogenic shock or cardiac arrest caused by massive pulmonary embolism. In these patients, positioning an inferior vena cava filter is often advisable, especially if deep venous thrombosis is not resolved at the time of the ECMO suspension. Moreover, in ECMO patients, a high incidence of deep venous thrombosis at the site of venous cannulation has been reported, and massive pulmonary embolism following ECMO decannulation has been described. Nonetheless, an inferior vena cava filter cannot be positioned as long as an ECMO cannula is inside the inferior vena cava. Thus, we developed a strategy to allow placement of an inferior vena cava filter through the internal jugular concurrently with the removal of the femoral venous ECMO cannula. In two women supported by veno-arterial ECMO for cardiac arrest secondary to pulmonary embolism, this novel approach allowed for safe ECMO decannulation. PMID- 27003433 TI - Delaying time to first nocturnal void may have beneficial effects on reducing blood glucose levels. AB - Experimental studies disrupting sleep and epidemiologic studies of short sleep durations indicate the importance of deeper and longer sleep for cardiometabolic health. We examined the potential beneficial effects of lengthening the first uninterrupted sleep period (FUSP) on blood glucose. Long-term data (>=3 months of treatment) were derived from three clinical trials, testing low-dose (10-100 ug) melt formulations of desmopressin in 841 male and female nocturia patients (90 % of which had nocturnal polyuria). We performed post hoc multiple regression with non-fasting blood glucose as dependent variable and the following potential covariates/factors: time-averaged change of FUSP since baseline, age, gender, race, ethnicity, baseline glucose, baseline weight, change in weight, patient metabolic status (normal, metabolic syndrome, type II diabetes), dose, follow-up interval, and time of random glucose sampling. Increases in FUSP resulted in statistically significant reductions in blood glucose (p = 0.0131), even after controlling for all remaining covariates. Per hour increase in time to first void was associated with glucose decreases of 1.6 mg/dL. This association was more pronounced in patients with increased baseline glucose levels (test of baseline glucose by FUSP change interaction: p < 0.0001). Next to FUSP change, other statistically significant confounding factors/covariates also associated with glucose changes were gender, ethnicity, metabolic subgroup, and baseline glucose. These analyses indicate that delaying time to first void may have beneficial effects on reducing blood glucose in nocturia patients. These data are among the first to suggest that improving sleep may have salutary effects on a cardiometabolic measure. PMID- 27003434 TI - Acute liver damage following intravenous glucocorticoid treatment for Graves' ophthalmopathy. AB - PURPOSE: Over the last years, there have been several reports on the occurrence of acute liver damage (ALD) in patients affected with Graves' ophthalmopathy (GO) receiving intravenous glucocorticoids (ivGCs). This article is aimed at reviewing the literature on this specific topic and reporting two new cases of ALD occurring in GO patients while on ivGCs. METHODS: The terms "glucocorticoid therapy" and "Graves' Ophthalmopathy"/"Graves' Orbitopathy"/"Thyroid eye disease" were used both separately and in conjunction with the terms "liver disease," "liver damage," "hepatotoxicity," "liver failure," to search MEDLINE for articles published since the first report of ALD in 2000 and up to 2015. RESULTS: ALD [defined as an increase in alanine aminotransferase (ALT) >300 U/L] during or after completion of ivGCs has been so far reported in 17 fully documented cases. Overall, one-half of those patients were diagnosed as having autoimmune hepatitis (AIH) and in the vast majority of the remaining cases a diagnosis of methylprednisolone(MP)-induced hepatotoxicity was suspected. The clinical course of liver injury varied from asymptomatic hypertransaminasemia in the vast majority of patients to fatal hepatic failure in four patients receiving higher (>8 g) cumulative doses of MP. CONCLUSIONS: The overall risk of ALD is relatively low (~1 %), and seems higher using a single dose >0.5 g and a cumulative dose >8.5 g MP. Whenever ivGC treatment is required, serum liver enzymes, viral hepatitis markers, and autoantibodies related to AIH should be obtained prior to ivGC administration. Liver function should be monitored during ivGC and up to 6 months after the end of treatment. Prolonging observation after 6 months is likely unnecessary, since all cases of ALD so far reported always occurred well within this term. PMID- 27003435 TI - Premixed insulin regimens in type 2 diabetes: pros. AB - Because of the increasing prevalence of type 2 diabetes, the need to intensify treatment to manage hyperglycemia is expanding. Premixed insulin regimens were designed to maximize patient convenience and reduce the number of daily injections required by providing both rapid-acting and intermediate-acting components in one formulation. Although the basal bolus insulin regimen is considered by many as "the golden standard" in reaching goals of glycemic control, proper use of intensified insulin regimens, such as basal bolus or premixed, will result in similar HbA1c reduction, hypoglycemic events, and weight gain. At the same number of daily insulin injections (2 shots/day), the premixed regimen is associated with a significant 0.2 % HbA1c decrease, as compared with the basal plus regimen (one shot of long-acting plus one shot of short-acting insulin). The choice of insulin regimen should consider the preferences, and resources of the individual and the family for adapting treatment to the patient needs. At last, the process of insulin initiation and intensification in type 2 diabetes must be carried out in the context of patient safety, minimizing the risk of hypoglycemia, weight gain, and injection burden. PMID- 27003436 TI - The prevalence and predictive value of the SLC30A8 R325W polymorphism and zinc transporter 8 autoantibodies in the development of GDM and postpartum type 1 diabetes. AB - The objectives were to evaluate possible associations between the SLC30A8 R325W polymorphism and gestational diabetes mellitus (GDM) as well as postpartum development of type 2 diabetes. Furthermore, we wanted to confirm the prevalence of zinc transporter 8 autoantibodies (ZnT8A), as previously reported, in a larger population and study its predictive value in relation to other beta cell specific autoantibodies in postpartum development of type 1 diabetes. Women diagnosed with GDM (n = 776) and women without diabetes (n = 511) were included in the study. Autoantibodies were analyzed in all women using enzyme-linked immunosorbent assay. DNA was extracted when possible from women with GDM (n = 536) and all of the controls. R325W was detected through polymerase chain reaction and specific restriction digestion. The R325W C-allele were more frequent in women with GDM compared to in controls (OR 1.47, 95 % CI 1.16-1.88, p = 0.0018) but not significantly increased in women with GDM and postpartum development of type 2 diabetes. Autoantibodies were found in 6.8 % (53/776) of the women with GDM and approximately 3.2 % (25/776) were ZnT8A positive. Approximately 19 % (10/53) of the autoantibody positive women with GDM developed postpartum type 1 diabetes. In conclusion, this is the first study to report a significant association between the R325W C-allele and increased risk of developing GDM. All of the autoantibody positive women with GDM who developed postpartum type 1 diabetes were positive for autoantibodies against glutamic acid decarboxylase (GADA). Thus ZnT8A did not have any additional predictive value in postpartum development of type 1 diabetes. PMID- 27003437 TI - Recent Progress in the Diagnosis of Pathogenic Candida Species in Blood Culture. AB - Candidemia has become an emerging invasive fungal disease. Prompt treatment with appropriate antifungal agent is crucial to reduce the mortality of candidemia. The conventional blood culture method, which is considered the gold standard for candidemia diagnosis, has a low sensitivity and is time-consuming to perform. Recently, several novel advanced diagnostic methods that have a higher sensitivity and a shorter turnaround time than the conventional blood culture method have been developed for the early detection of Candida in blood samples or in blood culture broth. Most of these newer methods were developed using various molecular techniques, such as matrix-assisted laser desorption/ionization time-of flight mass spectrometry, peptide nucleic acid fluorescence in situ hybridization, and a number of DNA-based techniques including in-house and commercial polymerase chain reactions. In this article, we review and summarize the novel molecular methods that have been recently used for the detection and identification of Candida organisms in blood specimens. PMID- 27003438 TI - Fine mapping and candidate gene analysis of an anthocyanin-rich gene, BnaA.PL1, conferring purple leaves in Brassica napus L. AB - Because of the advantages of anthocyanins, the genetics and breeding of crops rich in anthocyanins has become a hot research topic. However, due to the lack of anthocyanin-related mutants, no regulatory genes have been mapped in Brassica napus. In this study, we first report the characterization of a B. napus line with purple leaves and the fine mapping and candidate screening of the BnaA.PL1 gene. The amount of anthocyanins in the purple leaf line was six times higher than that in a green leaf line. A genetic analysis indicated that the purple character was controlled by an incomplete dominant gene. Through map-based cloning, we localized the BnaA.PL1 gene to a 99-kb region at the end of B. napus chromosome A03. Transcriptional analysis of 11 genes located in the target region revealed that the expression level of only the BnAPR2 gene in seedling leaves decreased from purple to reddish green to green individuals, a finding that was consistent with the measured anthocyanin accumulation levels. Molecular cloning and sequence analysis of BnAPR2 showed that the purple individual-derived allele contained 17 variants. Markers co-segregating with BnaA.PL1 were developed from the sequence of BnAPR2 and were validated in the BC4P2 population. These results suggested that BnAPR2, which encodes adenosine 5'-phosphosulfate reductase, is likely to be a valuable candidate gene. This work may lay the foundation for the marker-assisted selection of B. napus vegetables that are rich in anthocyanins and for an improved understanding of the molecular mechanisms controlling anthocyanin accumulation in Brassica. PMID- 27003439 TI - Pull or Push? Octopuses Solve a Puzzle Problem. AB - Octopuses have large brains and exhibit complex behaviors, but relatively little is known about their cognitive abilities. Here we present data from a five-level learning and problem-solving experiment. Seven octopuses (Octopus vulgaris) were first trained to open an L shaped container to retrieve food (level 0). After learning the initial task all animals followed the same experimental protocol, first they had to retrieve this L shaped container, presented at the same orientation, through a tight fitting hole in a clear Perspex partition (level 1). This required the octopuses to perform both pull and release or push actions. After reaching criterion the animals advanced to the next stage of the test, which would be a different consistent orientation of the object (level 2) at the start of the trial, an opaque barrier (level 3) or a random orientation of the object (level 4). All octopuses were successful in reaching criterion in all levels of the task. At the onset of each new level the performance of the animals dropped, shown as an increase in working times. However, they adapted quickly so that overall working times were not significantly different between levels. Our findings indicate that octopuses show behavioral flexibility by quickly adapting to a change in a task. This can be compared to tests in other species where subjects had to conduct actions comprised of a set of motor actions that cannot be understood by a simple learning rule alone. PMID- 27003440 TI - Generation and Standardized, Systemic Phenotypic Analysis of Pou3f3L423P Mutant Mice. AB - Increased levels of blood plasma urea were used as phenotypic parameter for establishing novel mouse models for kidney diseases on the genetic background of C3H inbred mice in the phenotype-driven Munich ENU mouse mutagenesis project. The phenotypically recessive mutant line HST011 was established and further analyzed. The causative mutation was detected in the POU domain, class 3 transcription factor 3 (Pou3f3) gene, which leads to the amino acid exchange Pou3f3L423P thereby affecting the conserved homeobox domain of the protein. Pou3f3 homozygous knockout mice are published and show perinatal death. Line Pou3f3L423P is a viable mouse model harboring a homozygous Pou3f3 mutation. Standardized, systemic phenotypic analysis of homozygous mutants was carried out in the German Mouse Clinic. Main phenotypic changes were low body weight and a state of low energy stores, kidney dysfunction and secondary effects thereof including low bone mineralization, multiple behavioral and neurological defects including locomotor, vestibular, auditory and nociceptive impairments, as well as multiple subtle changes in immunological parameters. Genome-wide transcriptome profiling analysis of kidney and brain of Pou3f3L423P homozygous mutants identified significantly regulated genes as compared to wild-type controls. PMID- 27003441 TI - Development of an Immunoassay for Chloramphenicol Based on the Preparation of a Specific Single-Chain Variable Fragment Antibody. AB - Specific antibodies are essential for the immune detection of small molecule contaminants. In the present study, the heavy and light variable regions (V(H )and V(L)) of the immunoglobulin genes from a hybridoma secreting a chloramphenicol (CAP)-specific monoclonal antibody (mAb) were cloned and sequenced. In addition, the light and heavy chains obtained from the monoclonal antibody were separated using SDS-PAGE and analyzed using Orbitrap mass spectrometry. The results of DNA sequencing and mass spectrometry analysis were compared, and the V(H) and V(L) chains specific for CAP were determined and used to construct a single-chain variable fragment (scFv). This fragment was recombinantly expressed as a soluble scFv-alkaline phosphatase fusion protein and used to develop a direct competitive ELISA. Compared with the parent mAb, scFv exhibits lower sensitivity but better food matrix resistance. This work highlights the application of engineered antibodies for CAP detection. PMID- 27003442 TI - GHR/PRLR Heteromultimer Is Composed of GHR Homodimers and PRLR Homodimers. AB - GH receptor (GHR) and prolactin (PRL) receptor (PRLR) are homologous transmembrane cytokine receptors. Each prehomodimerizes and ligand binding activates Janus Kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) signaling pathways by inducing conformational changes within receptor homodimers. In humans, GHR is activated by GH, whereas PRLR is activated by both GH and PRL. We previously devised a split luciferase complementation assay, in which 1 receptor is fused to an N-terminal luciferase (Nluc) fragment, and the other receptor is fused to a C-terminal luciferase (Cluc) fragment. When receptors approximate, luciferase activity (complementation) results. Using this assay, we reported ligand-independent GHR-GHR complementation and GH-induced complementation changes characterized by acute augmentation above basal signal, consistent with induction of conformational changes that bring GHR cytoplasmic tails closer. We also demonstrated association between GHR and PRLR in T47D human breast cancer cells by coimmunoprecipitation, suggesting that, in addition to forming homodimers, these receptors form hetero-assemblages with functional consequences. We now extend these analyses to examine basal and ligand-induced complementation of coexpressed PRLR-Nluc and PRLR-Cluc chimeras and coexpressed GHR-Nluc and PRLR-Cluc chimeras. We find that PRLR-PRLR and GHR-PRLR form specifically interacting ligand-independent assemblages and that either GH or PRL augments PRLR-PRLR complementation, much like the GH-induced changes in GHR-GHR dimers. However, in contrast to the complementation patterns for GHR-GHR or PRLR PRLR homomers, both GH and PRL caused decline in luciferase activity for GHR-PRLR heteromers. These and other data suggest that GHR and PRLR associate in complexes comprised of GHR-GHR/PRLR-PRLR heteromers consisting of GHR homodimers and PRLR homodimers, rather than GHR-PRLR heterodimers. PMID- 27003443 TI - Regulation of Energy Balance via BDNF Expressed in Nonparaventricular Hypothalamic Neurons. AB - Brain-derived neurotrophic factor (BDNF) expressed in the paraventricular hypothalamus (PVH) has been shown to play a key role in regulating energy intake and energy expenditure. BDNF is also expressed in other hypothalamic nuclei; however, the role in the control of energy balance for BDNF produced in these structures remains largely unknown. We found that deleting the Bdnf gene in the ventromedial hypothalamus (VMH) during embryogenesis using the Sf1-Cre transgene had no effect on body weight in mice. In contrast, deleting the Bdnf gene in the adult VMH using Cre-expressing virus led to significant hyperphagia and obesity. These observations indicate that the lack of a hyperphagia phenotype in the Sf1 Cre/Bdnf mutant mice is likely due to developmental compensation. To investigate the role of BDNF expressed in other hypothalamic areas, we employed the hypothalamus-specific Nkx2.1-Cre transgene to delete the Bdnf gene. We found that the Nkx2.1-Cre transgene could abolish BDNF expression in many hypothalamic nuclei, but not in the PVH, and that the resulting mutant mice developed modest obesity due to reduced energy expenditure. Thus, BDNF produced in the VMH plays a role in regulating energy intake. Furthermore, BDNF expressed in hypothalamic areas other than PVH and VMH is also involved in the control of energy expenditure. PMID- 27003444 TI - Research Resource: Roles for Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CaMKK2) in Systems Metabolism. AB - A number of epidemiological studies have implicated calcium (Ca(2+)) signaling as a major factor in obesity that contributes to aberrant systems metabolism. Somewhat paradoxically, obesity correlates with decreased circulating Ca(2+) levels, leading to increased release of intracellular Ca(2+) stores from the endoplasmic reticulum. These findings suggest that insulin resistance associated with the obese state is linked to activation of canonical Ca(2+) signaling pathways. Mechanistically, increased intracellular Ca(2+) binds calmodulin (CaM) to activate a set of Ca(2+)/CaM-dependent protein kinases. In this research resource, we explore the metabolic functions and implications of Ca(2+)/CaM dependent protein kinase kinase 2 (CaMKK2) as a metabolic effector of Ca(2+)/CaM action. We reveal the importance of CaMKK2 for gating insulin release from pancreatic beta-cells while concomitantly influencing the sensitivity of insulin responsive tissues. To provide a better understanding of the metabolic impact of CaMKK2 loss, we performed targeted metabolomic analyses of key metabolic byproducts of glucose, fatty acid, and amino acid metabolism in mice null for CaMKK2. We quantified amino acids and acyl carnitines in 3 insulin-sensitive tissues (liver, skeletal muscle, plasma) isolated from CaMKK2(-/-) mice and their wild-type littermates under conditions of dietary stress (low-fat diet, normal chow, high-fat diet, and fasting), thereby unveiling unique metabolic functions of CaMKK2. Our findings highlight CaMKK2 as a molecular rheostat for insulin action and emphasize the importance of Ca(2+)/CaM/CaMKK2 in regulation of whole body metabolism. These findings reveal that CaMKK2 may be an attractive therapeutic target for combatting comorbidities associated with perturbed insulin signaling. PMID- 27003445 TI - Adaptation-Induced Compression of Event Time Occurs Only for Translational Motion. AB - Adaptation to fast motion reduces the perceived duration of stimuli displayed at the same location as the adapting stimuli. Here we show that the adaptation induced compression of time is specific for translational motion. Adaptation to complex motion, either circular or radial, did not affect perceived duration of subsequently viewed stimuli. Adaptation with multiple patches of translating motion caused compression of duration only when the motion of all patches was in the same direction. These results show that adaptation-induced compression of event-time occurs only for uni-directional translational motion, ruling out the possibility that the neural mechanisms of the adaptation occur at early levels of visual processing. PMID- 27003446 TI - Classification of Promoters Based on the Combination of Core Promoter Elements Exhibits Different Histone Modification Patterns. AB - Four different histones (H2A, H2B, H3, and H4; two subunits each) constitute a histone octamer, around which DNA wraps to form histone-DNA complexes called nucleosomes. Amino acid residues in each histone are occasionally modified, resulting in several biological effects, including differential regulation of transcription. Core promoters that encompass the transcription start site have well-conserved DNA motifs, including the initiator (Inr), TATA box, and DPE, which are collectively called the core promoter elements (CPEs). In this study, we systematically studied the associations between the CPEs and histone modifications by integrating the Drosophila Core Promoter Database and time series ChIP-seq data for histone modifications (H3K4me3, H3K27ac, and H3K27me3) during development in Drosophila melanogaster via the modENCODE project. We classified 96 core promoters into four groups based on the presence or absence of the TATA box or DPE, calculated the histone modification ratio at the core promoter region, and transcribed region for each core promoter. We found that the histone modifications in TATA-less groups were static during development and that the core promoters could be clearly divided into three types: i) core promoters with continuous active marks (H3K4me3 and H3K27ac), ii) core promoters with a continuous inactive mark (H3K27me3) and occasional active marks, and iii) core promoters with occasional histone modifications. Linear regression analysis and non-linear regression by random forest showed that the TATA-containing groups included core promoters without histone modifications, for which the measured RNA expression values were not predictable accurately from the histone modification status. DPE-containing groups had a higher relative frequency of H3K27me3 in both the core promoter region and transcribed region. In summary, our analysis showed that there was a systematic link between the existence of the CPEs and the dynamics, frequency and influence on transcriptional activity of histone modifications. PMID- 27003447 TI - No evidence that HPV vaccination leads to sexual risk compensation. AB - Uptake of the HPV vaccine has been lower than the uptake of most other childhood vaccines offered in public programs. Since the HPV vaccine protects against a sexually transmitted virus, one barrier to uptake specific to the HPV vaccine may be the concern that vaccination may encourage risky sexual behaviour. Unanimous findings from recent studies show that HPV vaccination does not lead to sexual risk compensation, which is an important message to parents, clinicians and other decision-makers regarding HPV vaccination. Some issues remain to be investigated, like HPV vaccination and sexual risk compensation among boys. PMID- 27003449 TI - A Novel Glutamyl (Aspartyl)-Specific Aminopeptidase A from Lactobacillus delbrueckii with Promising Properties for Application. AB - Lactic acid bacteria (LAB) are auxotrophic for a number of amino acids. Thus, LAB have one of the strongest proteolytic systems to acquit their amino acid requirements. One of the intracellular exopeptidases present in LAB is the glutamyl (aspartyl) specific aminopeptidase (PepA; EC 3.4.11.7). Most of the PepA enzymes characterized yet, belonged to Lactococcus lactis sp., but no PepA from a Lactobacillus sp. has been characterized so far. In this study, we cloned a putative pepA gene from Lb. delbrueckii ssp. lactis DSM 20072 and characterized it after purification. For comparison, we also cloned, purified and characterized PepA from Lc. lactis ssp. lactis DSM 20481. Due to the low homology between both enzymes (30%), differences between the biochemical characteristics were very likely. This was confirmed, for example, by the more acidic optimum pH value of 6.0 for Lb-PepA compared to pH 8.0 for Lc-PepA. In addition, although the optimum temperature is quite similar for both enzymes (Lb-PepA: 60 degrees C; Lc-PepA: 65 degrees C), the temperature stability after three days, 20 degrees C below the optimum temperature, was higher for Lb-PepA (60% residual activity) than for Lc PepA (2% residual activity). EDTA inhibited both enzymes and the strongest activation was found for CoCl2, indicating that both enzymes are metallopeptidases. In contrast to Lc-PepA, disulfide bond-reducing agents such as dithiothreitol did not inhibit Lb-PepA. Finally, Lb-PepA was not product inhibited by L-Glu, whereas Lc-PepA showed an inhibition. PMID- 27003448 TI - The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. AB - Nanoparticle-based technologies offer exciting new approaches to disease diagnostics and therapeutics. To take advantage of unique properties of nanoscale materials and structures, the size, shape and/or surface chemistry of nanoparticles need to be optimized, allowing their functionalities to be tailored for different biomedical applications. Here we review the effects of nanoparticle size on cellular interaction and in vivo pharmacokinetics, including cellular uptake, biodistribution and circulation half-life of nanoparticles. Important features of nanoparticle probes for molecular imaging and modeling of nanoparticle size effects are also discussed. PMID- 27003450 TI - The Reliability of Functional Movement Screening and In-Season Changes in Physical Function and Performance Among Elite Rugby League Players. AB - This study aimed to (a) assess the reliability of the functional movement screening (FMS) protocol and (b) to establish changes in both FMS and tests of physical performance throughout a season. The reliability of the FMS components (12 in total) was assessed through a nonparametric statistical approach, based on 2 trials, separated by 1 week. Score on the FMS, strength (3 repetition maximum full squat, 1 repetition maximum [1 RM] bench press), running speed (10 and 40 m), and jump height of 12 elite male under-19 rugby league players was monitored at pre-, mid-, and late-season periods. There was no bias (p > 0.05) found between trials for the FMS, with the majority of components reaching 100% "perfect agreement," reflecting the good reliability of the FMS tool. There were no effects (p > 0.05) of season stage on any of the FMS components; however, an improvement (p <= 0.05) between the pre- and both mid- and late-season periods was apparent in every component of fitness, such as 1 RM bench press (112.92 +/- 24.54 kg; 125.83 +/- 21.41 kg; 125.98 +/- 24.48 kg) and 40-m sprint time (5.69 +/ 0.35 seconds; 5.62 +/- 0.31 seconds; 5.64 +/- 0.27 seconds). Our findings demonstrate that the FMS can be reliably administered to elite rugby league players but will not change in accordance with physical performance across a competitive season. Our findings should not necessarily deter practitioners from using the FMS but begin to question the specific qualities that are being assessed through its administration. PMID- 27003451 TI - The Effects of Attentional Focusing Instructions on Force Production During the Isometric Midthigh Pull. AB - Verbal instructions play a key role in motor learning and performance. Whereas directing one's attention toward bodily movements or muscles (internal focus) tends to hinder performance, instructing persons to focus on the movement outcome, or an external object related to the performed task (external focus) enhances performance. The study's purpose was to examine whether focus of attention affects maximal force production during an isometric midthigh pull (IMTP) among 18 trained athletes (8F & 10M). Athletes performed 3 IMTP trials a day for 3 consecutive days. The first day was a familiarization session in which athlete's received only control instructions. The following 2 days athletes received either control, internal, or external focus of attention instructions in a randomized, within-subject design. Compared to performance with an internal focus of attention, athletes applied 9% greater force when using an external focus of attention (p < 0.001, effect size [ES] = 0.33) and 5% greater force with control instructions (p = 0.001, ES = 0.28). A small positive 3% advantage was observed between performances with an external focus of attention compared with control instructions (p = 0.03, ES = 0.13). Focusing internally on body parts and/or muscle groups during a movement task that requires maximal force hinders performance, whereas focusing on an object external to the self leads to enhanced force production, even when using a simple multijoint static task such as the IMTP. PMID- 27003452 TI - Impact Forces of Walking and Running at the Same Intensity. AB - Moderate-intensity walking (horizontal, WH), vigorous-intensity walking (incline, WI), and vigorous-intensity running (horizontal, R) were compared. The hypothesis is that running creates greater loading forces than walking even at the same aerobic intensity. Young adults (10 M and 10 F; age, 22.8 +/- 0.5 years) performed 3 exercise trials in a counter-balanced order: walking 5.5 kph at 0% grade (WH); walking 5.5 kph at 11% (WI); and running at 8.0 kph at 0% (R). Oxygen consumption (V[Combining Dot Above]O2), step frequency, peak vertical ground reaction force (VGRF), and vertical force loading rate were recorded during the last 5 minutes of each trial. Results are mean +/- SE. Net V[Combining Dot Above]O2 during WH (10.5 +/- 0.3 ml.min.kg) was significantly less than WI (26.3 +/- 0.3) and R (25.1 +/- 0.7 ml.min.kg). Step frequency was significantly greater during R (163 +/- 1.5 steps per minute) than both walking conditions (WH, 128 +/- 1.0 steps per minute; WI, 126 +/- 1.2 steps per minute). Peak VGRF was significantly greater during running (844 +/- 47 N) than both walking conditions (WH, 581 +/- 27 N; WI, 565 +/- 28 N). Force loading rate was significantly greater with R (8,214 +/- 26 N.s) than WH (6,497 +/- 15 N.s ) and WI (5,699 +/- 16 N.s ), with WH > WI. Vigorous-intensity walking produced no greater loading forces than moderate-intensity walking. However, running at a vigorous intensity produced substantially greater loading forces than walking of the same intensity. These findings suggest that vigorous aerobic exercise may be performed without elevated orthopedic stress, depending on the mode prescribed. PMID- 27003453 TI - Influence of Compression and Stiffness Apparel on Vertical Jump Performance. AB - Compression apparel alters both compression of the soft tissues and the hip joint stiffness of athletes. It is not known whether it is the compression elements, the stiffness elements, or some combination that increases performance. Therefore, the purpose of this study was to determine how systematically increasing upper leg compression and hip joint stiffness independently from one another affects vertical jumping performance. Ten male athletes performed countermovement vertical jumps in 8 concept apparel conditions and 1 control condition (loose fitting shorts). The 8 apparel conditions, 4 that specifically altered the amount of compression exerted on the thigh and 4 that altered the hip joint stiffness by means of elastic thermoplastic polyurethane bands, were tested on 2 separate testing sessions (one testing the compression apparel and the other testing the stiffness apparel). Maximum jump height was measured, while kinematic data of the hip, knee, and ankle joint were recorded with a high-speed camera (480 Hz). Both compression and stiffness apparel can have a positive influence on vertical jumping performance. The increase in jump height for the optimal compression was due to increased hip joint range of motion and a trend of increasing the jump time. Optimal stiffness also increased jump height and had the trend of decreasing the hip joint range of motion and hip joint angular velocity. The exact mechanisms by which apparel interventions alter performance is not clear, but it may be due to alterations to the force-length and force velocity relationships of muscle. PMID- 27003454 TI - Effects of Jaw Clenching While Wearing a Customized Bite-Aligning Mouthpiece on Strength in Healthy Young Men. AB - Recent studies have investigated the ergogenic effects of different types of mouthguards. There is evidence of the benefits of clenching customized mouthpieces on force and power development. The phenomenon called concurrent activation potentiation (CAP) promoted in jaw clenching seems to enhance the muscular strength and power in maximal isometric contractions and powerful actions in sport. Moreover, a bite-aligning mouthpiece may promote a more aligned and powerful clench. The objective of the present study was to investigate the effects of jaw clenching while wearing a customized bite-aligning mouthpiece (MP) on jump ability and isometric maximal strength tests in contrast to 2 other conditions: nonjaw clenching (NON-JAW) and jaw clenching without the mouthpiece (JAW). A within-subjects design was used to assess the jump performance and the maximal isometric force in 28 physically active male subjects. Statistical analyses revealed significantly higher performance in JAW and NON-JAW conditions for handgrip force (HG-peakforce) and all variables of the back-row exercise (BRW) and countermovement vertical jump (CMVJ) (p <= 0.05). Significant differences between NON-JAW and JAW were found for HG-peakforce (p <= 0.05). These findings suggest that it is advisable to use a customized bite-aligning mouthpiece to improve strength and power performance. PMID- 27003455 TI - Variable Changes in Body Composition, Strength and Lower-Body Power During an International Rugby Sevens Season. AB - This study determined whether body composition, strength, and power changes that occur during preseason can be maintained during an international rugby sevens season. Fourteen male international rugby sevens players (age 21.4 +/- 2.2 years; mean +/- SD) were categorized as forward (n = 7) or back (n = 7), and assessed for height, mass (M), skinfolds (S) (?7), upper-body (UB) strength, lower-body (LB) strength, and LB power. Bench press, back squat, and a countermovement jump were used to measure strength and power at 3 time points: initial, early season, and late season. Forwards were taller (185 +/- 4 cm), heavier (95 +/- 6 kg), and possessed a greater lean body mass (55.5 +/- 4.0 M.S) than backs (181 +/- 8 cm, 88.5 +/- 5.5 kg, and 51.9 +/- 3.4 M.S). Over the full season, small (~5 +/- 5%; mean +/- 90% confidence limits) positive changes occurred in body composition. Lower-body strength gained during the preseason, decayed in-season, whereas UB strength increased moderately (~10 +/- 3%) across the season. Power showed inconsistencies between measured variables with a moderate positive change across the season in mean velocity and relative peak power. Forwards showed a small decrease in peak power (relative and absolute). Moderate changes were observed in mean power over the season, forwards decreasing (~6 +/- 6%) and backs increasing (~8 +/- 6%). Rugby sevens forwards in this study found it difficult to maintain and improve power qualities in-season. Training loads of forwards and backs should be differentiated to maximize strength and power in-season. PMID- 27003456 TI - Experimental Validation of Plastic Mandible Models Produced by a "Low-Cost" 3 Dimensional Fused Deposition Modeling Printer. AB - BACKGROUND: The objective of this study was to investigate the accuracy of 3 dimensional (3D) plastic (ABS) models generated using a low-cost 3D fused deposition modelling printer. MATERIAL/METHODS: Two human dry mandibles were scanned with a cone beam computed tomography (CBCT) Accuitomo device. Preprocessing consisted of 3D reconstruction with Maxilim software and STL file repair with Netfabb software. Then, the data were used to print 2 plastic replicas with a low-cost 3D fused deposition modeling printer (Up plus 2(r)). Two independent observers performed the identification of 26 anatomic landmarks on the 4 mandibles (2 dry and 2 replicas) with a 3D measuring arm. Each observer repeated the identifications 20 times. The comparison between the dry and plastic mandibles was based on 13 distances: 8 distances less than 12 mm and 5 distances greater than 12 mm. RESULTS: The mean absolute difference (MAD) was 0.37 mm, and the mean dimensional error (MDE) was 3.76%. The MDE decreased to 0.93% for distances greater than 12 mm. CONCLUSIONS: Plastic models generated using the low cost 3D printer UPplus2(r) provide dimensional accuracies comparable to other well-established rapid prototyping technologies. Validated low-cost 3D printers could represent a step toward the better accessibility of rapid prototyping technologies in the medical field. PMID- 27003457 TI - Thermogenesis induced by amino acid administration prevents intraoperative hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy. AB - Minimally invasive thoracoscopic esophagectomy has potential advantages in minimizing the impairment of respiratory function and reducing surgical stress. However, thoracoscopic esophagectomy occasionally results in anesthesia-induced hypothermia, particularly in cases involving artificial pneumothorax with CO2. Thermogenesis induced by amino acid administration has been reported during anesthesia. Here, we tested the efficacy of amino acid treatment for the prevention of hypothermia, and we investigated the potential of this treatment to reduce postoperative infectious complications after thoracoscopic esophagectomy. We conducted a randomized trial in patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position in two groups and analyzed the incidences of hypothermia and surgical complications. One-hundred and thirty patients were randomized. Administration of amino acids resulted in a significant increase in core body temperature. In the saline (n = 60) and amino acid (n = 70) administration groups, 30% and 14.2% of patients, respectively, experienced infectious surgical complications (P = 0.029), and 21.6% and 22.8% of patients, respectively, experienced noninfectious surgical complications (P = 0.86). Univariate analysis revealed that blood loss and amino acid administration were significant factors for infectious surgical complications. Multivariate analysis revealed that amino acid administration was an independent factor reducing infectious surgical complications (P = 0.025, 95% confidence interval: 0.105 0.864). Administration of amino acids prevents hypothermia and reduces postoperative infectious complications after thoracoscopic esophagectomy. PMID- 27003458 TI - Association of Vitamin D with outcome after intra cytoplasmic sperm injection. AB - OBJECTIVE: To observe effects of vitamin D levels on pregnancy outcome after intra cytoplasmic sperm injection (ICSI). METHOD: It was a cross-sectional study conducted in Australian Concept Infertility Medical Center from July 2011 to August 2014. Estimation of 25-hydroxy cholecalciferol (25-OHD) of consented females (252) was done before treatment protocol for ICSI. Results of beta hCG performed 14 days after embryo transfer categorized groups; Pregnant with beta hCG more than 25 IU/mL and rest included in non-pregnant group. Both groups were compared by independent sample t-test and Pearson's Chi Square test. Binary Logistic Regression Analysis was used to estimate odds ratio of pregnancy outcome with its predictors including Vitamin D. RESULTS: The mean value of 25-OHD, number of oocytes, fertilized oocytes and endometrial thickness was significantly higher in pregnant women. A significant positive association of 25-OHD with clinical pregnancy and thickness of endometrium was observed. After adjustment with female age and BMI, positive association of vitamin D with endometrial thickness was observed. CONCLUSION: Deficiency of 25-OHD in females hinders the accomplishment of optimal endometrial thickness required for implantation of embryo after ICSI. The improvement in vitamin D status can thus improve success results in assisted reproductive clinics. PMID- 27003459 TI - Kinetic and molecular characterization of the pyruvate phosphate dikinase from Trypanosoma cruzi. AB - Trypanosoma cruzi, like other trypanosomatids analyzed so far, can use both glucose and amino acids as carbon and energy source. In these parasites, glycolysis is compartmentalized in glycosomes, authentic but specialized peroxisomes. The major part of this pathway, as well as a two-branched glycolytic auxiliary system, are present in these organelles. The first enzyme of one branch of this auxiliary system is the PPi-dependent pyruvate phosphate dikinase (PPDK) that converts phosphoenolpyruvate (PEP), inorganic pyrophosphate (PPi) and AMP into pyruvate, inorganic phosphate (Pi) and ATP, thus contributing to the ATP/ADP balance within the glycosomes. In this work we cloned, expressed and purified the T. cruzi PPDK. It kinetic parameters were determined, finding KM values for PEP, PPi and AMP of 320, 70 and 17 MUM, respectively. Using molecular exclusion chromatography, two native forms of the enzyme were found with estimated molecular weights of 200 and 100 kDa, corresponding to a homodimer and monomer, respectively. It was established that T. cruzi PPDK's specific activity can be enhanced up to 2.6 times by the presence of ammonium in the assay mixture. During growth of epimastigotes in batch culture an apparent decrease in the specific activity of PPDK was observed. However, when its activity is normalized for the presence of ammonium in the medium, no significant modification of the enzyme activity per cell in time was found. PMID- 27003460 TI - Identification and characterization of profilin antigen among Babesia species as a common vaccine candidate against babesiosis. AB - We have characterized a member of the profilin (PROF) family protein as a common antigen in three pathogens-Babesia bovis (B. bovis), Babesia bigemina (B. bigemina), and Babesia microti (B. microti)-and evaluated its immunogenic and cross-protective properties against a challenge infection with B. microti in BALB/c mice. The recombinant PROF proteins of B. bovis, B. bigemina, and B. microti were successfully expressed in Escherichia coli (E. coli) as soluble GST fusion proteins (rBboPROF, rBbigPROF, and rBmPROF, respectively), and they were found to be antigenic. On probing with mouse anti-rPROF serum, green fluorescence was observed on the parasites' cytosols by confocal laser microscopy. Immunization regimes in BALB/c mice using rPROFs induced cross-protective immunity against B. microti infection based on high levels of cytokines and immunoglobulin (IgG) titers, a reduction in peak parasitemia levels, and earlier clearance of the parasite as compared with control mice. The findings of the present study indicate that PROF is a common antigen among bovine and murine Babesia parasites, and it might be used as a common vaccine candidate against babesiosis. PMID- 27003461 TI - Surface binding properties of aged and fresh (recently excreted) Toxoplasma gondii oocysts. AB - The surfaces of aged (10 years) and fresh (recently excreted) oocysts of Toxoplasma gondii were investigated using monoclonal antibody (mAb) and lectin binding assays. Fresh oocysts bound a wall-specific mAb labelled with fluorescein isothiocyanate while aged oocysts did not. In contrast, the walls of aged oocysts bound a lectin (wheat germ agglutinin, WGA), but not the walls of fresh oocysts. Exposure of oocysts to detergent solutions or trypsin did not affect the binding properties of the walls of the oocysts. However, exposure of fresh oocysts to acidified pepsin enabled labelling of the walls with WGA, presumably due to the relevant moieties on the oocyst walls becoming exposed. WGA binding, but not mAb binding, was partially abrogated with periodate exposure. These findings reveal a significant difference in the binding properties of oocyst walls from "aged" and "fresh" oocysts. The results are of relevance when considering technologies for isolating or detecting T. gondii oocysts in environmental samples based on oocyst surface properties, as used for other protozoan parasites. Our results suggest the possibility of developing a WGA-based separation procedure for isolating Toxoplasma oocysts from environmental matrices, in which pepsin pre-treatment would be included to ensure that both fresh and aged oocysts were isolated. PMID- 27003463 TI - [Not Available]. PMID- 27003464 TI - The predictive distribution of the residual variability in the linear-fixed effects model for clinical cross-over trials. AB - In the linear model for cross-over trials, with fixed subject effects and normal i.i.d. random errors, the residual variability corresponds to the intraindividual variability. While population variances are in general unknown, an estimate can be derived that follows a gamma distribution, where the scale parameter is based on the true unknown variability. This gamma distribution is often used for the sample size calculation for trial planning with the precision approach, where the aim is to achieve in the next trial a predefined precision with a given probability. But then the imprecision in the estimated residual variability or, from a Bayesian perspective, the uncertainty of the unknown variability is not taken into account. Here, we present the predictive distribution for the residual variability, and we investigate a link to the F distribution. The consequence is that in the precision approach more subjects will be necessary than with the conventional calculation. For values of the intraindividual variability that are typical of human pharmacokinetics, that is a gCV of 17-36%, we would need approximately a sixth more subjects. PMID- 27003465 TI - The role of surface modification for TiO2 nanoparticles in cancer cells. AB - Titanium dioxide nanoparticles (TiO2 NPs) have a potential in the field of biological application. However, its poor dispersibility in water hampered its applications. In this study, 3-phosphonopropionic acid and 3-aminopropyl triethoxysilane were respectively used for surface modification on TiO2 NPs with negative and positive surface charges (denoted as TiO2-COOH and TiO2-NH2). Zeta potentials of the prepared samples with high absolute value demonstrate the great improvement in their dispersibility. In terms of viability experiment, both TiO2 COOH and TiO2-NH2 showed low cytotoxicity. The cellular uptake efficiency and the uptake pathways of TiO2-COOH and TiO2-NH2 for cancer cells were studied. The exocytosis of TiO2-NH2 was also observed in the experiment. PMID- 27003466 TI - Ultra-flexible nanocarriers for enhanced topical delivery of a highly lipophilic antioxidative molecule for skin cancer chemoprevention. AB - PURPOSE: In this study, we developed cationic ultra-flexible nanocarriers (UltraFLEX-Nano) to surmount the skin barrier structure and to potentiate the topical delivery of a highly lipophilic antioxidative diindolylmethane derivative (DIM-D) for the inhibition of UV-induced DNA damage and skin carcinogenesis. METHODS: UltraFLEX-Nano was prepared with 1,2-dipalmitoyl-sn-glycero-3 phosphocholine, 1,2-dioleoyl-3-trimethylammonium-propane, cholesterol and tween 80 by ethanolic injection method; was characterized by Differential Scanning Calorimetric (DSC), Fourier Transform Infrared (FT-IR) and Atomic Force Microscopic (phase-imaging) analyses and permeation studies were performed in dermatomed human skin. The efficacy of DIM-D-UltraFLEX-Nano for skin cancer chemoprevention was evaluated in UVB-induced skin cancer model in vivo. RESULTS: DIM-D-UltraFLEX-Nano formed a stable mono-dispersion (110.50+/-0.71nm) with >90% encapsulation of DIM-D that was supported by HPLC, DSC, FT-IR and AFM phase imaging. The blank formulation was non-toxic to human embryonic kidney cells. UltraFLEX-Nano was vastly deformable and highly permeable across the stratum corneum; there was significant (p<0.01) skin deposition of DIM-D for UltraFLEX Nano that was superior to PEG solution (13.83-fold). DIM-D-UltraFLEX-Nano pretreatment delayed the onset of UVB-induced tumorigenesis (2 weeks) and reduced (p<0.05) the number of tumors observed in SKH-1 mice (3.33-fold), which was comparable to pretreatment with sunscreen (SPF30). Also, DIM-D-UltraFLEX-Nano caused decrease (p<0.05) in UV-induced DNA damage (8-hydroxydeoxyguanosine), skin inflammation (PCNA), epidermal hyperplasia (c-myc, CyclinD1), immunosuppression (IL10), cell survival (AKT), metastasis (Vimentin, MMP-9, TIMP1) but increase in apoptosis (p53 and p21). CONCLUSION: UltraFLEX-Nano was efficient in enhancing the topical delivery of DIM-D. DIM-D-UltraFLEX-Nano was efficacious in delaying skin tumor incidence and multiplicity in SKH mice comparable to sunscreen (SPF30). PMID- 27003468 TI - A Quality by design (QbD) approach on starch-based nanocapsules: A promising platform for topical drug delivery. AB - Exploring novel applications for approved excipients with a history of safe use in therapeutics is a smart strategy to obtain improved pharmaceutical products. The present study aimed at developing a novel starch-based nanoparticulate carrier system (StNC) for topical delivery of lipophilic bioactive molecules. The role of the different factors that affect the particle size distribution and zeta potential of StNC prepared by the emulsification-solvent evaporation method was assessed using a quality by design approach. An optimal formulation was selected and fully characterized in terms of molecular interactions (DSC and FTIR), morphology (TEM and AFM), as well as in vitro and in vivo biological properties, including biological sensitivity/irritation studies performed in human volunteers. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. In addition, all tested formulations presented a zeta potential of ca. +33.6+/-6.7 mV, indicating a good physical stability, while revealing an excellent compromise between stability, safety and cosmeticity, evidencing that StNC are suitable nanocarriers for topical use. Finally, the design planning methodology has clearly shown its usefulness for optimizing the formulation, being also crucial for the understanding of StNC formation process. The StNC proved to be a promising formulation strategy and a potential nanocarrier for topical lipophilic bioactive molecules. PMID- 27003467 TI - Smart lipid nanoparticles containing levofloxacin and DNase for lung delivery. Design and characterization. AB - Levofloxacin (LV) is a hydrophilic broad-spectrum antibiotic commonly used in pulmonary treatment against recurrent infections of Pseudomonas aeruginosa, and particularly in cystic fibrosis (CF) disease. In order to study feasible carriers for LV, solid lipid nanoparticles (SLN) of myristyl myristate were prepared by the ultrasonication method in the presence of Pluronic((r))F68 under different experimental conditions and characterized by dynamic light scattering, optical, transmission and scanning electron microscopy for size and morphology. Alternatively, nanostructured lipid carriers (NLCs) were developed to improve LV encapsulation and storage. SLN showed 20.1+/-1.4% LV encapsulation efficiency, while the NLCs encapsulated 55.9+/-1.6% LV. NLC formulation exhibited a more controlled release profile than SLN formulation, but both showed a biphasic drug release pattern with burst release at the first 5h and prolonged release afterwards, demonstrated by in vitro tests. The hydrodynamic average diameter and zeta potential of NLC were 182.6+/-3.2nm and -10.2+/-0.2mV, respectively, and were stable for at least 3 months. Additionally, DNase type I was incorporated into the formulations as a "smart" component, since the enzyme could help to decrease the viscoelasticity found in the lungs of CF patients and improves the antibiotic diffusion. FTIR, XRD, DSC, TGA and nitrogen adsorption isotherms of the nanoparticles indicate the presence of the loads in a noncrystalline state. The developed formulation showed an active antimicrobial activity against P. aeruginosa and even against other opportunistic pathogens such as Staphylococcus aureus. The presence of LV-loaded NLCs reduced the formation of a bacterial biofilm, which highlighted the significance of the nanodevice as a new alternative for CF treatment. PMID- 27003470 TI - MOF-Based Membrane Encapsulated ZnO Nanowires for Enhanced Gas Sensor Selectivity. AB - Gas sensors are of a great interest for applications including toxic or explosive gases detection in both in-house and industrial environments, air quality monitoring, medical diagnostics, or control of food/cosmetic properties. In the area of semiconductor metal oxides (SMOs)-based sensors, a lot of effort has been devoted to improve the sensing characteristics. In this work, we report on a general methodology for improving the selectivity of SMOx nanowires sensors, based on the coverage of ZnO nanowires with a thin ZIF-8 molecular sieve membrane. The optimized ZnO@ZIF-8-based nanocomposite sensor shows markedly selective response to H2 in comparison with the pristine ZnO nanowires sensor, while showing the negligible sensing response to C7H8 and C6H6. This original MOF membrane encapsulation strategy applied to nanowires sensor architecture pave the way for other complex 3D architectures and various types of applications requiring either gas or ion selectivity, such as biosensors, photo(catalysts), and electrodes. PMID- 27003471 TI - Layer-by-layer assembly of versatile nanoarchitectures with diverse dimensionality: a new perspective for rational construction of multilayer assemblies. AB - Over the past few decades, layer-by-layer (LbL) assembly of multilayer thin films has garnered considerable interest on account of its ability to modulate nanometer control over film thickness and its extensive choice of usable materials for coating planar and particulate substrates, thus allowing for the fabrication of responsive and functional thin films for their potential applications in a myriad of fields. Herein, we provide elaborate information on the current developments of LbL assembly techniques including different properties, molecular interactions, and assembly methods associated with this promising bottom-up strategy. In particular, we highlight the principle for rational design and fabrication of a large variety of multilayer thin film systems including multi-dimensional capsules or spatially hierarchical nanostructures based on the LbL assembly technique. Moreover, we discuss how to judiciously choose the building block pairs when exerting the LbL assembly buildup which enables the engineering of multilayer thin films with tailor-made physicochemical properties. Furthermore, versatile applications of the diverse LbL-assembled nanomaterials are itemized and elucidated in light of specific technological fields. Finally, we provide a brief perspective and potential future challenges of the LbL assembly technology. It is anticipated that our current review could provide a wealth of guided information on the LbL assembly technique and furnish firm grounds for rational design of LbL assembled multilayer assemblies toward tangible applications. PMID- 27003472 TI - Psychological health in long-term cancer survivorship: an Italian survey on depression and anxiety. AB - Since long-term survivorship is now a reality for an increasingly number of people with a history of cancer, understanding their psychological health can inform health care policy as well as help supporting individual patients. This study was aimed to describe depression and anxiety (i.e. two of the most common psychological symptoms reported in oncology) in a sample of Italian long-term cancer survivors (LTCSs) defined as people who have been free from cancer and cancer treatments for at least five years. Four hundred and four Italian adult LTCSs completed a battery of questionnaires including the Zung Self-rating Depression Scale and the State Anxiety sub-scale of the State-Trait Anxiety Inventory respectively for depression and anxiety assessment. 16.5% of the sample displayed mild depression, 11.1% moderate depression, and 7.1% severe depression. depression was negatively associated with education (p = .017), perceived social support as provided by the family (p = .028), and perceived social support provided by friends (p = .008), and it was positively associated with occupational status (p = .023), presence of health issues (p = .010), and anxiety (p < .001). 8.7 and 15.8% of the sample were respectively possible and probable cases of anxiety. Anxiety was negatively associated with occupational status (p = .038) and it was positively associated with depression (p < .001). These data support ongoing assessment and monitoring of depression and anxiety in LTCSs, and stimulate the development and testing of psychological interventions for such individuals. In addition, they encourage further study on the psychological health of this specific population. PMID- 27003473 TI - Mass spectrometry-based identification of allergens from Curvularia pallescens, a prevalent aerospore in India. AB - The worldwide prevalence of fungal allergy in recent years has augmented mining allergens from yet unexplored ones. Curvularia pallescens (CP) being a dominant aerospore in India and a major sensitiser on a wide range of allergic population, pose a serious threat to human health. Therefore, we aimed to identify novel allergens from CP in our present study. A cohort of 22 CP-sensitised patients was selected by positive Skin prick grade. Individual sera exhibited elevated specific IgE level and significant histamine release on a challenge with antigenic extract of CP. First gel-based profiling of CP proteome was done by 1- and 2-dimensional gel. Parallel 1- and 2-dimensional immunoblot were performed applying individual as well as pooled patient sera. Identification of the sero reactive spots from the 2-dimensional gel was found to be challenging as CP was not previously sequenced. Hence, mass spectrometry-based proteomic workflow consisting of conventional database search was not alone sufficient. Therefore, de novo sequencing preceded homology search was implemented for further identification. Altogether 11 allergenic proteins including Brn-1, vacuolar protease, and fructose-bis-phosphate aldolase were identified with high statistical confidence (p<0.05). This is the first study to report on any allergens from CP. This kind of proteome-based analysis provided a catalogue of CP allergens that would lead an improved way of diagnosis and therapy of CP related allergy. PMID- 27003476 TI - Providing a Voice for Our Littlest Patients: Strategies for Writing Case of the Month Manuscripts. PMID- 27003478 TI - Ankyloglossia and the Breastfeeding Infant: Assessment and Intervention. AB - BACKGROUND: Our current culture defines breastfeeding and the use of human breast milk as the preferred criterion standard for infant nutrition. Medical and health professionals have a responsibility to support breastfeeding in the mother-infant dyad. This includes the recognition of anatomical barriers to breastfeeding such as a tongue-tie, ankyloglossia. PURPOSE: The purpose of this article is to enrich and expand the clinical knowledge of health professionals about the physical assessment of ankyloglossia and its impact on breastfeeding. Techniques for assessing anterior and posterior ankyloglossia and interventions across the spectrum are discussed. We also explore maternal emotional experiences of breastfeeding an infant with ankyloglossia. METHODS/SEARCH STRATEGY: A systematic literature search from MEDLINE, CINAHL, and Cochrane databases was performed. The search results consisted of qualitative and quantitative studies performed involving infants with anykloglossia and breastfeeding experiences. Data and findings from the search results were analyzed and reviewed. FINDINGS: Ankyloglossia, commonly referred to as tongue-tied, can result in weight loss, painful breastfeeding, and a cessation of breastfeeding prematurely. Depending on severity, interventions to alleviate breastfeeding difficulties can range from a lactation consultation to surgical intervention. The options for treatment and intervention must be discussed thoroughly with caregivers. IMPLICATIONS FOR PRACTICE: Thorough assessment of the breastfeeding dyad is essential to discovering ankyloglossia and its role in breastfeeding difficulties. Intervening appropriately can prevent negative outcomes associated with ankyloglossia and breastfeeding. IMPLICATIONS FOR RESEARCH: Future studies should be focused on developing universal tools for grading ankyloglossia and the effects of ankyloglossia on speech development. There is also a gap in the knowledge regarding ankyloglossia in the preterm infant and its impact on developing breast and bottle-feeding technique in the neonatal intensive care unit. PMID- 27003474 TI - Effect of Outer-Sphere Side Chain Substitutions on the Fate of the trans Iron Nitrosyl Dimer in Heme/Nonheme Engineered Myoglobins (Fe(B)Mbs): Insights into the Mechanism of Denitrifying NO Reductases. AB - Denitrifying NO reductases are transmembrane protein complexes that utilize a heme/nonheme diiron center at their active sites to reduce two NO molecules to the innocuous gas N2O. Fe(B)Mb proteins, with their nonheme iron sites engineered into the heme distal pocket of sperm whale myoglobin, are attractive models for studying the molecular details of the NO reduction reaction. Spectroscopic and structural studies of Fe(B)Mb constructs have confirmed that they reproduce the metal coordination spheres observed at the active site of the cytochrome c dependent NO reductase from Pseudomonas aeruginosa. Exposure of Fe(B)Mb to excess NO, as examined by analytical and spectroscopic techniques, results primarily in the formation of a five-coordinate heme-nitrosyl complex without N2O production. However, substitution of the outer-sphere residue Ile107 with a glutamic acid (i.e., I107E) decreases the formation rate of the five-coordinate heme-nitrosyl complex and allows for the substoichiometric production of N2O. Here, we aim to better characterize the formation of the five-coordinate heme-nitrosyl complex and to explain why the level of N2O production increases with the I107E substitution. We follow the formation of the five-coordinate heme-nitrosyl inhibitory complex through the sequential exposure of Fe(B)Mb to different NO isotopomers using rapid-freeze-quench resonance Raman spectroscopy. The data show that the complex is formed by the displacement of the proximal histidine by a new NO molecule after the weakening of the Fe(II)-His bond in the intermediate six coordinate low-spin (6cLS) heme-nitrosyl complex. These results lead us to explore diatomic migration within the scaffold of myoglobin and whether substitutions at residue 107 can be sufficient to control access to the proximal heme cavities. Results on a new Fe(B)Mb construct with an I107F substitution (Fe(B)Mb3) show an increased rate for the formation of the five-coordinate low spin heme-nitrosyl complex without N2O production. Taken together, our results suggest that production of N2O from the [6cLS heme {FeNO}(7)/{Fe(B)NO}(7)] trans iron-nitrosyl dimer intermediate requires a proton transfer event facilitated by an outer-sphere residue such as E107 in Fe(B)Mb2 and E280 in P. aeruginosa cNOR. PMID- 27003480 TI - Chronic Recurrent Vogt-Koyanagi-Harada Disease and Development of 'Sunset Glow Fundus' Predict Worse Retinal Sensitivity. AB - PURPOSE: To investigate prognostic factors for retinal sensitivity assessed by microperimetry in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: In total, 34 patients with initial-onset acute disease and 19 patients with chronic recurrent disease were retrospectively evaluated. RESULTS: The mean follow-up period was 40.4 +/- 40.5 months. Sensitivity was significantly worse in eyes with more severe anterior segment inflammation at presentation, as indicated by the presence of mutton-fat keratic precipitates, anterior chamber reaction >=2+, and posterior synechiae. Chronic recurrent presentation, development of complications, and 'sunset glow fundus' were significantly associated with worse sensitivity. Using logistic regression analysis, better sensitivity was significantly associated with initial-onset acute presentation (odds ratio, OR = 6.9; 95% confidence interval, CI = 1.53-9.66). CONCLUSIONS: Chronic recurrent presentation and development of complications and 'sunset glow fundus' are associated with a worse sensitivity outcome. PMID- 27003481 TI - rFRET: A comprehensive, Matlab-based program for analyzing intensity-based ratiometric microscopic FRET experiments. AB - Fluorescence or Forster resonance energy transfer (FRET) remains one of the most widely used methods for assessing protein clustering and conformation. Although it is a method with solid physical foundations, many applications of FRET fall short of providing quantitative results due to inappropriate calibration and controls. This shortcoming is especially valid for microscopy where currently available tools have limited or no capability at all to display parameter distributions or to perform gating. Since users of multiparameter flow cytometry usually apply these tools, the absence of these features in applications developed for microscopic FRET analysis is a significant limitation. Therefore, we developed a graphical user interface-controlled Matlab application for the evaluation of ratiometric, intensity-based microscopic FRET measurements. The program can calculate all the necessary overspill and spectroscopic correction factors and the FRET efficiency and it displays the results on histograms and dot plots. Gating on plots and mask images can be used to limit the calculation to certain parts of the image. It is an important feature of the program that the calculated parameters can be determined by regression methods, maximum likelihood estimation (MLE) and from summed intensities in addition to pixel-by-pixel evaluation. The confidence interval of calculated parameters can be estimated using parameter simulations if the approximate average number of detected photons is known. The program is not only user-friendly, but it provides rich output, it gives the user freedom to choose from different calculation modes and it gives insight into the reliability and distribution of the calculated parameters. (c) 2016 International Society for Advancement of Cytometry. PMID- 27003482 TI - Editorial. PMID- 27003483 TI - Beyond Empathy: The Tree of Compassion With Malevolent Ego States. AB - Therapy with seriously dissociated patients requires the transformation and integration of malevolent ego states that produce a wide assortment of negative experiences and behaviors in the patient. During the course of therapy, they can present dangers to both patient and therapist, as well as to the therapeutic process (Watkins & Watkins, 1984). Perhaps the greatest challenges for therapists in this work are the development and the maintenance of empathy for these personality aspects. Without some degree of empathy, a healing therapeutic alliance cannot be formed, and absent a secure, healing, intersubjective experience, it is unlikely that malevolent ego states can undergo sufficient transformation for integration. Essential elements for developing and sustaining both the necessary empathy and the compassion, the altruistic activity that empathy engenders, are presented. PMID- 27003484 TI - Advantageous Use of Hypnosis in a Case of Psychogenic Vomiting. AB - This case study describes in detail the role of hypnosis in treatment of a case of psychogenic vomiting. The patient, a 60-yearold woman, had been suffering for 9 months from episodes of vomiting which resulted in weight loss, dehydration, and hypokalemia. She was a conscientious woman with high standards of behavior, which did not allow an expression of the extreme hostility she felt toward her daughter-in-law. Hypnotherapeutic sessions reduced her anxiety, restored her sleep, improved mood, and helped deepen rapport, all of which created the ideal setting for Gestalt's empty chair technique. Integrating hypnosis greatly enhanced the quality of the empty chair dialogue, which by bringing about a shift in the patient's emotions from hostility to sympathy, facilitated recovery. PMID- 27003485 TI - A Case Study of Hypnosis for Phagophobia: It's No Choking Matter. AB - In this case study the author reviews the benefits of hypnosis for a 13-year-old female suffering from a specific phobia involving a fear of choking and generalized fear of swallowing that resulted in an episode of Restrictive Food Intake Disorder with associated significant weight loss. At the time of the initial consultation, three weeks after her choking episode, the patient weighed 93 pounds. Standing at 5'2", her Body Mass Index (BMI) was 17 (15th percentile) indicative of healthy weight for a child her age and height. She continued to lose weight over the course of 2 months and at her worst weighed 85 pounds (BMI = 15.5, 3rd percentile, classified as underweight). Prior to the incident, she weighed 105 pounds with a BMI of 19.2 (46th percentile). Treatment initially consisted of 12 hypnosis sessions (over a 5-month period), conducted on a weekly and eventually biweekly basis. A scheduled one-month follow-up visit was conducted following the 12th session, at which time the patient was consuming solid foods without fear of choking. Her BMI at that time was 18.7 (39th percentile). Two months after terminating treatment, the patient experienced a mild relapse triggered by conflicts with some female peers. After four additional hypnosis sessions, the patient's symptoms again remitted. During her last session we shared a pizza, providing clear and convincing evidence that she had overcome her fear of swallowing. She retained therapeutic benefits for at least 3 years following treatment. PMID- 27003486 TI - Impact of Hypnosis Intervention in Alleviating Psychological and Physical Symptoms During Pregnancy. AB - Physical symptoms (e.g., vomiting) and psychological symptoms (stress, anxiety, and depression) during pregnancy are common. Various strategies such as hypnosis are available to reduce these symptoms. The objective of the authors in this study is to investigate the impact of a hypnosis intervention in reducing physical and psychological symptoms during pregnancy. A pre-test/post-test quasi experimental design was employed in this study. The hypnosis intervention was given to the experimental group participants at weeks 16 (baseline), 20 (time point 1), 28 (time point 2), and 36 (time point 3) of their pregnancy. Participants in the control group received only the traditional antenatal care. Participants from both groups completed the Depression Anxiety Stress Scale-21 (DASS-21) and a Pregnancy Symptoms Checklist at weeks 16, 20, 28 and 36 of pregnancy. Results indicated that stress and anxiety symptoms were significantly reduced for the experimental group, but not for the control group. Although mean differences for the depressive symptoms were not significant, the experimental group had lower symptoms at time point 3. The physical symptoms' results showed significant group differences at time point 3, indicating a reduction in the experience of physical symptoms for the experimental group participants. Our study showed that hypnosis intervention during pregnancy aided in reducing physical and psychological symptoms during pregnancy. PMID- 27003487 TI - Hypnosis and Mindfulness: The Twain Finally Meet. AB - Mindfulness meditation (or simply mindfulness) is an ancient method of attention training. Arguably, developed originally by the Buddha, it has been practiced by Buddhists over 2,500 years as part of their spiritual training. The popularity in mindfulness has soared recently following its adaptation as Mindfulness-Based Stress Management by Jon Kabat-Zinn (1995). Mindfulness is often compared to hypnosis but not all assertions are accurate. This article, as a primer, delineates similarities and dissimilarities between mindfulness and hypnosis in terms of 12 specific facets, including putative neuroscientific findings. It also provides a case example that illustrates clinical integration of the two methods. PMID- 27003488 TI - Using Hypnosis to Enhance Learning Second Language Vocabulary. AB - In this article, we measure the effects of hypnosis and suggestions for learning second language vocabulary. Participants (N = 70) were randomly assigned to a hypnosis or a control group. They were pre-tested, and then presented 21 Spanish words, post-tested immediately and 1 week later. The data were analyzed using repeated measures analysis of variance with group (experimental versus control) as the between-subjects factor, and time as the within-subjects factor. The experimental group performed significantly better in both tests. Our results indicate that hypnosis is beneficial for second language vocabulary learning and retrieval. PMID- 27003489 TI - Are Anesthesia Providers Ready for Hypnosis? Anesthesia Providers' Attitudes Toward Hypnotherapy. AB - This study sought to measure current attitudes toward hypnosis among anesthesia providers using an in-person survey distributed at a single grand rounds at a single academic teaching hospital. One hundred twenty-six anesthesia providers (anesthesiologists and nurse anesthetists) were included in this study. A 10 question Institutional Review Board (IRB)-approved questionnaire was developed. One hundred twenty-six (73% of providers at the meeting) anesthesia providers completed the survey. Of the respondents, 54 (43%) were anesthesiologists, 42 (33%) were trainees (interns/residents/fellows) in anesthesia, and 30 (24%) were nurse anesthetists. Over 70% of providers, at each level of training, rated their knowledge of hypnosis as either below average or having no knowledge. Fifty-two (42%) providers agreed or strongly agreed that hypnotherapy has a place in the clinical practice of anesthesia, while 103 (83%) believed that positive suggestion has a place in the clinical practice of anesthesia (p < .0001). Common reasons cited against using hypnosis were that it is too time consuming (41%) and requires special training (34%). Only three respondents (2%) believed that there were no reasons for using hypnosis in their practice. These data suggest that there is a self-reported lack of knowledge about hypnosis among anesthesia providers, although many anesthesia providers are open to the use of hypnosis in their clinical practice. Anesthesia providers are more likely to support the use of positive suggestion in their practice than hypnosis. Practical concerns should be addressed if hypnosis and therapeutic verbal techniques are to gain more widespread use. PMID- 27003491 TI - Psychoaerobics: An Experiential Method to Empower Therapist Excellence by Zeig, Jeffrey K. PMID- 27003490 TI - Tranceforming Ericksonian Methods: Methods 21st Century Visions by Loriedo, Camillo, Zeig, Jeffrey, and Nardone, Giorgio. PMID- 27003492 TI - Review of the International Literature. PMID- 27003493 TI - Fracture Prediction With Modified-FRAX in Older HIV-Infected and Uninfected Men. AB - BACKGROUND: FRAX is a validated, computer-based clinical fracture risk calculator that estimates the 10-year risk of major osteoporotic (clinical spine, forearm, hip, or shoulder) fracture, and hip fracture alone. It is widely used for decision making in fracture prevention, but it may underestimate the risk in HIV infected individuals. Some experts recommend considering HIV as a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals. METHODS: From the Veterans Aging Cohort Study Virtual Cohort, we included 24,451 HIV-infected and uninfected men aged 50-70 years with complete data in the year 2000 to approximate all but 2 factors (ie, history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10 year observational data for incident fragility fracture. The accuracy of the modified-FRAX calculation was compared by the observed/estimated (O/E) ratios of fracture by HIV status. RESULTS: The accuracy of modified-FRAX was less for HIV infected [O/E = 1.62, 95% confidence interval (CI) 1.45 to 1.81] than uninfected men (O/E = 1.29, 95% CI: 1.19 to 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E = 1.20, 95% CI: 1.08 to 1.34). However, only 3%-6% of men with incident fractures were correctly identified by the modified FRAX using accepted FRAX thresholds for pharmacologic therapy. CONCLUSIONS: Modified-FRAX underestimated the fracture rates more in older HIV-infected than in otherwise similar uninfected men. The accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV infected individuals. PMID- 27003494 TI - Implementation and Operational Research: Impact of Nurse-Targeted Care on HIV Outcomes Among Immunocompromised Persons: A Before-After Study in Uganda. AB - INTRODUCTION: Improving HIV outcomes among severely immunocompromised HIV infected persons who have increased morbidity and mortality remains an important issue in sub-Saharan Africa. We sought to evaluate the impact of targeted clinic based nurse care on antiretroviral therapy (ART) initiation and retention among severely immunocompromised HIV-infected persons. METHODS: The study included ART naive patients with CD4 counts <100 cells per microliter registered in seven urban clinics in Kampala, Uganda. Data were retrospectively collected on patients enrolled from July to December 2011 (routine care cohort). Between July 2012 and September 2013, 1 additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation, and trace those who were lost to follow-up. We compared time to ART initiation and 6-month retention in care between cohorts and used a generalized linear model to estimate the relative risk of retention. RESULTS: The study included 258 patients in the routine care cohort and 593 in the nurse counselor cohort. The proportion of patients who initiated ART increased from 190 (73.6%) in the routine care cohort to 506 (85.3%) in the nurse counselor cohort (P < 0.001). At 6 months, 62% of the routine care cohort were retained in care versus 76% in the nurse counselor cohort (P = 0.001). A 21% increase in the likelihood of retention in the nurse counselor cohort (relative risk: 1.21, 95% CI: 1.09 to 1.34) compared with the routine care cohort was observed. CONCLUSIONS: Implementation of targeted nurse-led care of severely immunocompromised HIV-infected patients in public outpatient health care facilities resulted in decreased time to ART initiation and increased retention. PMID- 27003495 TI - FOXP3+Helios+ Regulatory T Cells, Immune Activation, and Advancing Disease in HIV Infected Children. AB - Regulatory T cells (Tregs) are functionally suppressive CD4 T cells, critical for establishing peripheral tolerance and controlling inflammatory responses. Previous reports of Tregs during chronic HIV disease have conflicting results with higher or lower levels compared with controls. Identifying true Tregs with suppressive activity proves challenging during HIV infection, as traditional Treg markers, CD25 and FOXP3, may transiently upregulate expression as a result of immune activation (IA). Helios is an Ikaros family transcription factor that marks natural Tregs with suppressive activity and does not upregulate expression after activation. Coexpression of FOXP3 and Helios has been suggested as a highly specific marker of "bona fide" Tregs. We evaluated Treg subsets by FOXP3 coexpressed with either CD25 or Helios and their association with HIV disease progression in perinatally infected HIV-positive children. Identifying Tregs by FOXP3 coexpression with Helios rather than CD25 revealed markedly higher Treg frequencies, particularly in HIV+ children. Regardless of antiretroviral therapy, HIV-infected children had a selective expansion of memory FOXP3+Helios+ Tregs. The rise in memory Tregs correlated with declining HIV clinical status, indicated by falling CD4 percentages and CD4:CD8 ratios and increasing HIV plasma viremia and IA. In addition, untreated HIV+ children exhibited an imbalance between the levels of Tregs and activated T cells. Finally, memory Tregs expressed IA markers CD38 and Ki67 and exhaustion marker, PD-1, that tightly correlated with a similar phenotype in memory CD4 T cells. Overall, HIV-infected children had significant disruptions of memory Tregs that associated with advancing HIV disease. PMID- 27003496 TI - Frequent HIV Testing: Impact on HIV Risk Among Chinese Men Who Have Sex with Men. AB - BACKGROUND: The HIV epidemic continues to expand among men who have sex with men (MSM) in China. The NIMH Project Accept/HPTN 043 trial suggested a borderline significant trend toward HIV incidence reduction among persons with higher testing rates. METHODS: We assessed HIV testing histories and infection status among a community-based Beijing MSM. HIV serostatus was lab confirmed. We ascertained demographic/behavioral factors through questionnaire-based interviews. Associations of previous HIV testing with odds of current HIV infection were assessed, seeking improved like-with-like risk comparisons through multivariable logistic regression analysis with propensity score adjustment and restricted cubic spline modeling. RESULTS: Among 3588 participants, 12.7% were HIV infected; 70.8% reported having ever tested for HIV. Compared with MSM who never tested, those ever testing had a 41% reduction in the odds of being HIV positive [adjusted odds ratio (aOR): 0.59; 95% confidence interval (CI): 0.48 to 0.74. Higher HIV testing frequencies were associated with a decreasing trend in the odds of being infected with HIV vs. a referent group with no previous testing [>6 tests (aOR: 0.27; 95% CI: 0.18 to 0.41); 4-6 (aOR: 0.55; 95% CI: 0.39 to 0.78); 2-3 (aOR: 0.61; 95% CI: 0.45 to 0.82); P for trend <0.001]. The multivariable-adjusted model with restricted cubic spline of HIV testing frequency showed a higher frequency of previous HIV testing associated with lower odds of HIV infection, particularly among men with >=10 lifetime male sexual partners. CONCLUSIONS: Using risk probability adjustments to enable less biased comparisons, frequent HIV testing was associated with a lower HIV odds among Chinese MSM. PMID- 27003497 TI - Brief Report: L-Selectin (CD62L) Is Downregulated on CD4+ and CD8+ T Lymphocytes of HIV-1-Infected Individuals Naive for ART. AB - The expression of L-selectin (CD62L) in HIV-1 infection has not been extensively investigated. Here, we measured CD62L expression on T-cell subsets of HIV-1 infected individuals naive for antiretroviral therapy (ART-naive) or receiving therapy (ART), and seronegative control subjects (HIV-neg). We found reduced frequencies of CD62L(+) cells among CD4(+) and CD8(+) T cells from ART-naive as compared with ART and HIV-neg groups, particularly within naive and central memory subsets. CD62L expression on T cells inversely correlated with viral load and rapidly increased after ART initiation. Plasma sCD62L levels did not correlate with CD62L expression, being higher in all HIV-1-infected individuals as compared with HIV-neg subjects. Finally, CD62L downregulation was found associated with the expression of the CD38 activation marker in CD8(+) T cells, but not in CD4(+) T cells. We suggest that CD62L downregulation due to unconstrained HIV-1 replication may have important consequences for T-cell circulation and function and for disease progression. PMID- 27003498 TI - Stabilizing nanocellulose-nonionic surfactant composite foams by delayed Ca induced gelation. AB - Aggregation of dispersed rod-like particles like nanocellulose can improve the strength and rigidity of percolated networks but may also have a detrimental effect on the foamability. However, it should be possible to improve the strength of nanocellulose foams by multivalent ion-induced aggregation if the aggregation occurs after the foam has been formed. Lightweight and highly porous foams based on TEMPO-mediated oxidized cellulose nanofibrils (CNF) were formulated with the addition of a non-ionic surfactant, pluronic P123, and CaCO3 nanoparticles. Foam volume measurements show that addition of the non-ionic surfactant generates wet CNF/P123 foams with a high foamability. Foam bubble size studies show that delayed Ca-induced aggregation of CNF by gluconic acid-triggered dissolution of the CaCO3 nanoparticles significantly improves the long-term stability of the wet composite foams. Drying the Ca-reinforced foam at 60 degrees C results in a moderate shrinkage and electron microscopy and X-ray tomography studies show that the pores became slightly oblate after drying but the overall microstructure and pore/foam bubble size distribution is preserved after drying. The elastic modulus (0.9-1.4 MPa) of Ca-reinforced composite foams with a density of 9-15 kg/m(3) is significantly higher than commercially available polyurethane foams used for thermal insulation. PMID- 27003499 TI - Experimental and theoretical studies on the corrosion inhibition of copper by two indazole derivatives in 3.0% NaCl solution. AB - Corrosion experiments and theoretical calculations were performed to investigate the inhibition mechanism of indazole (IA) and 5-aminoindazole (AIA) for copper in NaCl solution. The results obtained from weight loss and electrochemical experiments are in good agreement, and reveal that these compounds are high efficiency inhibitors with inhibition efficiency order: AIA>IA, which was further confirmed by field emission scanning electronic microscope (FESEM) observation. Besides, the quantum chemical calculations and molecular dynamics (MD) simulation showed that both studied inhibitors are adsorbed strongly on the copper surface in parallel mode. The adsorption of these molecules on copper substrate was found to obey Langmuir isotherm. PMID- 27003500 TI - Effect of gel matrix confinement on the solvent dynamics in supramolecular gels. AB - Supramolecular gels formed by the sugar gelator of methyl-4,6-O-(p nitrobenzylidene)-alpha-d-glucopyranoside (1) with 1,3-propanediol (PG) and 1 butanol (BU) were prepared with different gelator concentrations. The solvent dynamics within gels, characterized by the diffusion coefficient (D) and the spin lattice relaxation time (T1), was the subject of NMR diffusometry and relaxometry studies. The diffusion was studied as a function of diffusion time and gelator concentrations. The relaxation time was measured as a function of Larmor frequency. The decrease of the diffusion coefficient was observed as a function of diffusion time for both gels and for all studied gelator concentrations. It is indicative of the confinement effect due to the geometrical restrictions of the gel matrix. The relaxation data for PG solvent confined in 1/PG gel revealed the low frequency dispersion (in kHz region) which is a fingerprint of a specific interaction experienced by PG solvents in the presence of the rigid structure of gelator 1 aggregates. The relaxation model, well known from the interpretation of liquid confined in nanopores as reorientations mediated by translational displacements (RMTD), was successfully applied to analyze the data of studied solvents confined in matrices of supramolecular gels. The microstructures of gel matrices were imaged by Polarized Microscopy. PMID- 27003501 TI - Drought-Proofing Groundwater. PMID- 27003502 TI - Construction and Validation of a Self-Efficacy Scale for Latex Barrier Use. AB - Some studies have concluded there is a relationship between perceived self efficacy and behaviors that prevent HIV transmission. This paper presents the construction and validation of the latex barrier use self-efficacy scale (LBSS), which 480 participants filled out. Exploratory factor analysis yielded two components: positive expectations of self-efficacy (ES-POS) and negative expectations of self-efficacy (ES-NEG), which together accounted for 65.59% of total variance. That structure was later verified through confirmatory factor analysis. Internal consistency was .80 for the total scale, and .78 for each of the two factors. Moreover, the instrument had adequate convergent validity and was positively related with condom use self-efficacy, attitudes toward condom and latex barrier use, and ability to refuse sex if the partner refuses to use preventive methods. In conclusion, this instrument is a useful measure of self efficacy in latex barrier use. PMID- 27003503 TI - Enhanced Intracranial Microdialysis by Reduction of Traumatic Penetration Injury at the Probe Track. AB - Microdialysis provides deep insight into chemical neuroscience by enabling in vivo intracranial chemical monitoring. Nevertheless, implanting a microdialysis probe causes a traumatic penetration injury (TPI) of brain tissue at the probe track. The TPI, which is clearly documented by voltammetry and histochemical imaging, is a drawback because it perturbs the exact tissue from which the brain dialysate samples are derived. Our goal is to reduce, if not eventually eliminate, the TPI and its detrimental effects on neurochemical monitoring. Here, we demonstrate that combining a 5-day wait period after probe implantation with the continuous retrodialysis of a low-micromolar concentration of dexamethasone vastly reduces the TPI. Our approach to reducing the TPI reinstates normal evoked dopamine release activity in the tissue adjacent to the microdialysis probe, brings evoked dopamine release at the probe outlet into quantitative agreement with evoked dopamine release next to the probe, reinstates normal immunoreactivity for tyrosine hydroxylase and the dopamine transporter near the probe track, and greatly suppresses glial activation and scaring near the probe track. This reduction of the TPI and reinstatement of normal evoked dopamine release activity adjacent to the probe track appears to be due to dexamethasone's anti-inflammatory actions. PMID- 27003504 TI - Sensitive Visual Detection of AHPND Bacteria Using Loop-Mediated Isothermal Amplification Combined with DNA-Functionalized Gold Nanoparticles as Probes. AB - Acute hepatopancreatic necrosis disease (AHPND) is a component cause of early mortality syndrome (EMS) of shrimp. In 2013, the causative agent was found to be unique isolates of Vibrio parahaemolyticus (VPAHPND) that contained a 69 kbp plasmid (pAP1) carrying binary Pir-like toxin genes PirvpA and PirvpB. In Thailand, AHPND was first recognized in 2012, prior to knowledge of the causative agent, and it subsequently led to a precipitous drop in shrimp production. After VPAHPND was characterized, a major focus of the AHPND control strategy was to monitor broodstock shrimp and post larvae for freedom from VPAHPND by nucleic acid amplification methods, most of which required use of expensive and sophisticated equipment not readily available in a shrimp farm setting. Here, we describe a simpler but equally sensitive approach for detection of VPAHPND based on loop-mediated isothermal amplification (LAMP) combined with unaided visual reading of positive amplification products using a DNA-functionalized, ssDNA labled nanogold probe (AuNP). The target for the special set of six LAMP primers used was the VPAHPND PirvpA gene. The LAMP reaction was carried out at 65 degrees C for 45 min followed by addition of the red AuNP solution and further incubation at 65 degrees C for 5 min, allowing any PirvpA gene amplicons present to hybridize with the probe. Hybridization protected the AuNP against aggregation, so that the solution color remained red upon subsequent salt addition (positive test result) while unprotected AuNP aggregated and underwent a color change from red to blue and eventually precipitated (negative result). The total assay time was approximately 50 min. The detection limit (100 CFU) was comparable to that of other commonly-used methods for nested PCR detection of VPAHPND and 100-times more sensitive than 1-step PCR detection methods (104 CFU) that used amplicon detection by electrophoresis or spectrophotometry. There was no cross reaction with DNA templates derived from non-AHPND bacteria commonly found in shrimp ponds (including other Vibrio species). The new method significantly reduced the time, difficulty and cost for molecular detection of VPAHPND in shrimp hatchery and farm settings. PMID- 27003505 TI - The Ebb and Flow of Airborne Pathogens: Monitoring and Use in Disease Management Decisions. AB - Perhaps the earliest form of monitoring the regional spread of plant disease was a group of growers gathering together at the market and discussing what they see in their crops. This type of reporting continues to this day through regional extension blogs, by crop consultants and more formal scouting of sentential plots in the IPM PIPE network (http://www.ipmpipe.org/). As our knowledge of plant disease epidemiology has increased, we have also increased our ability to detect and monitor the presence of pathogens and use this information to make management decisions in commercial production systems. The advent of phylogenetics, next generation sequencing, and nucleic acid amplification technologies has allowed for development of sensitive and accurate assays for pathogen inoculum detection and quantification. The application of these tools is beginning to change how we manage diseases with airborne inoculum by allowing for the detection of pathogen movement instead of assuming it and by targeting management strategies to the early phases of the epidemic development when there is the greatest opportunity to reduce the rate of disease development. While there are numerous advantages to using data on inoculum presence to aid management decisions, there are limitations in what the data represent that are often unrecognized. In addition, our understanding of where and how to effectively monitor airborne inoculum is limited. There is a strong need to improve our knowledge of the mechanisms that influence inoculum dispersion across scales as particles move from leaf to leaf, and everything in between. PMID- 27003506 TI - Newly Emerged Populations of Plasmopara halstedii Infecting Rudbeckia Exhibit Unique Genotypic Profiles and Are Distinct from Sunflower-Infecting Strains. AB - The oomycete Plasmopara halstedii emerged at the onset of the 21st century as a destructive new pathogen causing downy mildew disease of ornamental Rudbeckia fulgida (rudbeckia) in the United States. The pathogen is also a significant global problem of sunflower (Helianthus annuus) and is widely regarded as the cause of downy mildew affecting 35 Asteraceae genera. To determine whether rudbeckia and sunflower downy mildew are caused by the same genotypes, population genetic and phylogenetic analyses were performed. A draft genome assembly of a P. halstedii isolate from sunflower was generated and used to design 15 polymorphic simple sequence repeat (SSR) markers. SSRs and two sequenced phylogenetic markers measured differentiation between 232 P. halstedii samples collected from 1883 to 2014. Samples clustered into two main groups, corresponding to host origin. Sunflower-derived samples separated into eight admixed subclusters, and rudbeckia derived samples further separated into three subclusters. Pre-epidemic rudbeckia samples clustered separately from modern strains. Despite the observed genetic distinction based on host origin, P. halstedii from rudbeckia could infect sunflower, and exhibited the virulence phenotype of race 734. These data indicate that the newly emergent pathogen populations infecting commercial rudbeckia are a different species from sunflower-infecting strains, notwithstanding cross infectivity, and genetically distinct from pre-epidemic populations infecting native rudbeckia hosts. PMID- 27003507 TI - A Genome-Wide Association Study for Partial Resistance to Maize Common Rust. AB - Quantitative resistance to maize common rust (causal agent Puccinia sorghi) was assessed in an association mapping population of 274 diverse inbred lines. Resistance to common rust was found to be moderately correlated with resistance to three other diseases and with the severity of the hypersensitive defense response previously assessed in the same population. Using a mixed linear model accounting for the confounding effects of population structure and flowering time, genome-wide association tests were performed based at 246,497 single nucleotide polymorphism loci. Three loci associated with maize common rust resistance were identified. Candidate genes at each locus had predicted roles, mainly in cell wall modification. Other candidate genes included a resistance gene and a gene with a predicted role in regulating accumulation of reactive oxygen species. PMID- 27003508 TI - Relationship of Soil Properties and Sugarcane Yields to Red Stripe in Louisiana. AB - Symptoms of red stripe disease caused by Acidovorax avenae subsp. avenae in Louisiana between 1985 and 2010 were limited to the leaf stripe form, which caused no apparent yield loss. During 2010, the more severe top rot form was observed, and a study was initiated to investigate the distribution of red stripe in the field and determine its effects on cane and sugar yields. Soil properties data, red stripe incidence, and sugarcane yields were all highly variable and were not randomly distributed in the field. Combined harvest data showed a negative correlation between yield components and red stripe incidence, with the strongest relationship between sucrose per metric ton and disease incidence. Red stripe incidence was positively correlated with several soil properties, including phosphorus, potassium, zinc, and calcium. Red stripe incidence also was found to increase with increasing nitrogen rate, with the greatest effects in heavy soils. Results also indicated that using red-stripe-infected cane as a seed source can significantly decrease shoot emergence, stalk population, and subsequent cane and sugar yields. These combined data suggest that red stripe disease can exhibit a highly variable rate of infection in commercial sugarcane fields and may also significantly decrease sugar yields. PMID- 27003509 TI - Lithium and bipolar disorder: Impacts from molecular to behavioural circadian rhythms. AB - Bipolar disorder (BD) is a severe and common psychiatric disorder. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. Lithium (Li) is the first-line treatment in BD, and its therapeutic action has been related to its ability to alter circadian rhythms. We systematically searched the PubMed database until January 2016, aiming to critically examine published studies investigating direct and indirect effects of Li on circadian rhythms. The results, from the 95 retained studies, indicated that Li: acts directly on the molecular clocks; delays the phase of sleep-wakefulness rhythms and the peak elevation of diurnal cycle body temperature; reduces the amplitude and shortens the duration of activity rhythms and lengthens free-running rhythms. Chronic Li treatment stabilizes free-running activity rhythms, by improving day-to-day rhythmicity of the activity, with effects that appear to be dose related. Pharmacogenetics demonstrate several associations of Li's response with circadian genes (NR1D1, GSK3beta, CRY1, ARNTL, TIM, PER2). Finally, Li acts on the retinal-hypothalamic pineal pathway, influencing light sensitivity and melatonin secretion. Li is a highly investigated chronobiologic agent, and although its chronobiological effects are not completely understood, it seems highly likely that they constitute an inherent component of its therapeutic action in the treatment of mood disorders. PMID- 27003510 TI - Heavy Element Effects in the Diagonal Born-Oppenheimer Correction within a Relativistic Spin-Free Hamiltonian. AB - Methodologies beyond the Born-Oppenheimer (BO) approximation are nowadays important to explain high precision spectroscopic measurements. Most previous evaluations of the BO correction are, however, focused on light-element molecules and based on a nonrelativistic Hamiltonian, so no information about the BO approximation (BOA) breakdown in heavy-element molecules is available. The present work is the first to investigate the BOA breakdown for the entire periodic table, by considering scalar relativistic effects in the Diagonal BO correction (DBOC). In closed shell atoms, the relativistic EDBOC scales as Z(1.25) and the nonrelativistic EDBOC scales as Z(1.17), where Z is the atomic number. Hence, we found that EDBOC becomes larger in heavy element atoms and molecules, and the relativistic EDBOC increases faster than nonrelativistic EDBOC. We have further investigated the DBOC effects on properties such as potential energy curves, spectroscopic parameters, and various energetic properties. The DBOC effects for these properties are mostly affected by the lightest atom in the molecule. Hence, in X2 or XAt molecule (X = H, Li, Na, K, Rb, and Cs) the effect of DBOC systematically decreases when X becomes heavier but in HX molecules, the effect of DBOC seems relatively similar among all the molecules. PMID- 27003511 TI - A Comprehensive Review of Recent Studies on Herb-Drug Interaction: A Focus on Pharmacodynamic Interaction. AB - OBJECTIVES: The concomitant use of herbal and conventional drugs accelerates the possibility of clinically significant herb-drug interactions (HDIs). This paper aims to analyze the current status of HDI studies worldwide and to review studies on HDI-induced pharmacodynamic (PD) interactions. METHODS: HDI studies published from 2000 to 2014 and indexed in PubMed were categorized according to publication year, area/country, study methods and objectives, and disease categories. The reviewed studies focused on HDI-induced PD; each PD interaction with concurrent use of approximately 100 herbal drugs and 70 conventional drugs was summarized. All PD-related articles were categorized according to four characteristics: herbal drugs, conventional drugs, types of PD interaction, and type of study. Among them, 17 well-designed clinical studies were evaluated by using the Jadad Quality Assessment Scale. RESULTS: The number of HDI reports has gradually increased since 2000, with a primary focus on neoplasms and diseases of the circulatory system. Most of these investigated pharmacokinetic reactions, such as cytochrome P450 enzyme metabolism, with fewer reports investigating PD. Most PD interaction studies investigated warfarin, ginkgo leaves, and St. John's wort. An evaluation of 17 studies revealed a generally positive view of PD effects involving synergism or reduced toxicity and a high average quality score (>3 points on a 0-5 scale). CONCLUSIONS: These results demonstrate that most HDI studies so far have examined PK interactions and have been limited to very few conventional drugs and herbal drugs. This suggests that more studies focusing on PD are necessary to understand interactions between commonly used herbal and conventional drugs. PMID- 27003512 TI - A Comparison of the Characteristics of Acupuncture- and Non-Acupuncture-Preferred Consumers: A Secondary Analysis of NHIS 2012 Data. AB - OBJECTIVES: To determine whether acupuncture use, sociodemographic characteristics, and existing health conditions differ between acupuncture preferred consumers (i.e., those who deem acupuncture to be one of the three most important complementary and alternative medicine [CAM] modalities used) and non acupuncture-preferred consumers who used acupuncture in the past 12 months METHODS: This is a secondary analysis of the National Health Interview Survey Sample Adult File and Adult Alternative Medicine datasets collected by the Centers for Disease Control and Prevention during 2012. The sample was drawn from the noninstitutionalized civilian population of the United States. The datasets yielded 34,525 respondents aged 18 years and older. Measures included in the analysis were acupuncture use in the past 12 months, sociodemographic characteristics, and existing health conditions. Analyses were performed by using Stata software, version 9.0 (Stata Corp., College Station, TX). RESULTS: Of the 10,158 adults who responded to the question regarding the "three most important" CAM modalities used, 572 (5.6%) had used acupuncture in the past 12 months. Of these, 456 (79.7%) chose acupuncture as one of the top three CAM modalities most important to their health. Acupuncture-preferred consumers reported significantly more visits to acupuncturists (7.46 versus 3.99 visits; p < 0.001), as well as higher out-of-pocket costs ($342.8 versus $246.4; p < 0.001), compared with non acupuncture-preferred consumers. The logistic regression model revealed that with every additional CAM modality used, the likelihood of deeming acupuncture as one of the three CAM modalities most important to one's health decreased by 39% (odds ratio, 0.61; 95% confidence interval, 0.52-0.71; p < 0.001). Health conditions were not statistically significant predictors. CONCLUSIONS: A consumer's preference for acupuncture appeared not to be driven by health conditions but rather was related to sociodemographic factors. This suggests that health education regarding acupuncture may need to be tailored to certain consumer groups, such as those residing in the South, and could provide more information on the comparative effectiveness of acupuncture for various health conditions. PMID- 27003513 TI - A Blue-Light-Emitting BODIPY Probe for Lipid Membranes. AB - Here we describe a new BODIPY-based membrane probe (1) that provides an alternative to dialkylcarbocyanine dyes, such as DiI-C18, that can be excited in the blue spectral region. Compound 1 has unbranched octadecyl chains at the 3,5 positions and a meso-amino function. In organic solvents, the absorption and emission maxima of 1 are determined mainly by solvent acidity and dipolarity. The fluorescence quantum yield is high and reaches 0.93 in 2-propanol. The fluorescence decays are well fitted with a single-exponential in pure solvents and in small and giant unilamellar vesicles (GUV) with a lifetime of ca. 4 ns. Probe 1 partitions in the same lipid phase as DiI-C18(5) for lipid mixtures containing sphingomyelin and for binary mixtures of dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC). The lipid phase has no effect on the fluorescence lifetime but influences the fluorescence anisotropy. The translational diffusion coefficients of 1 in GUVs and OLN-93 cells are of the same order as those reported for DiI-C18. The directions of the absorption and emission transition dipole moments of 1 are calculated to be parallel. This is reflected in the high steady-state fluorescence anisotropy of 1 in high ordered lipid phases. Molecular dynamic simulations of 1 in a model of the DOPC bilayer indicate that the average angle of the transition moments with respect to membrane normal is ca. 70 degrees , which is comparable with the value reported for DiI-C18. PMID- 27003514 TI - The catalytic activity of TET2 is essential for its myeloid malignancy suppressive function in hematopoietic stem/progenitor cells. PMID- 27003515 TI - A triad of telomerase, androgen receptor and early growth response 1 in prostate cancer cells. AB - Telomerase activation is one of the key mechanisms that allow cells to bypass replicative senescence. Telomerase activity is primarily regulated at the level of transcription of its catalytic unit- hTERT. Prostate cancer (PCa), akin to other cancers, is characterized by high telomerase activity. Existing data suggest that hTERT expression and telomerase activity are positively regulated by androgenic stimuli in androgen-dependent prostate cancer (ADPC) cells. A part of the present study reaffirmed this by demonstrating a decline in the hTERT expression and telomerase activity on "loss of AR" in ADPC cells. The study further addressed 2 unresolved queries, i) whether AR-mediated signaling is of any relevance to hTERT expression in castration-resistant prostate cancer (CRPC) and ii) whether this signaling involves EGR1. Our data suggest that AR-mediated signaling negatively regulates hTERT expression in CRPC cells. Incidental support for the possibility of EGR1 being a regulator of hTERT expression in PCa was provided by i) immunolocalization of hTERT and EGR1 proteins in the same cell type (secretory epithelium) of PCa and BPH tissues; ii) significantly (p< 0.001) higher levels of both these proteins in CRPC (PC3 and DU145), compared with ADPC (LNCaP) cells. A direct evidence for the role of EGR1 in hTERT expression was evident by a significant (p<0.0001) decrease in the hTERT transcript levels in the EGR1-silenced CRPC cells. Further, "gain of AR" led to a significant reduction in the levels of hTERT and EGR1 in CRPC cells. However, restoration of EGR1 levels prevented the decline in the hTERT transcript levels in these cells. Taken together, our data indicate that AR regulates the expression of EGR1, which in turn acts as a positive regulator of hTERT expression in CRPC cells. Thus, AR exerts an inhibitory effect on hTERT expression and telomerase activity by modulating EGR1 levels in CRPC cells. PMID- 27003517 TI - Intravitreal Ranibizumab and Aqueous Humor Factors/Cytokines in Major and Macular Branch Retinal Vein Occlusion. AB - Aqueous humor levels of cytokines and growth/inflammatory factors were measured in 38 patients with macular edema who had major branch retinal vein occlusion (BRVO) or macular BRVO and were treated with intravitreal ranibizumab injection (IRI). Patients with recurrence of macular edema received further IRI as needed. Aqueous humor levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1), and other cytokines/factors were measured. Compared with major BRVO, macular BRVO was associated with lower aqueous humor levels of sVEGFR 1, its ligands (VEGF and placental growth factor), and other growth/inflammatory factors (platelet-derived growth factor-AA, monocyte chemotactic protein-1, soluble intercellular adhesion molecule-1, interleukin-6, and interleukin-8). The mean number of IRI over 6 months was significantly lower in the macular BRVO group than in the major BRVO group. These findings suggest that macular BRVO requires fewer IRI than major BRVO and is associated with lower aqueous humor levels of various growth/inflammatory factors and cytokines. PMID- 27003518 TI - On the Simple Complexity of Carbon Monoxide on Oxide Surfaces: Facet-Specific Donation and Backdonation Effects Revealed on TiO2 Anatase Nanoparticles. AB - Atomic-scale relationships between the structure of TiO2 surfaces and the physicochemical properties of surface sites, functional for titania-based applications, can be obtained from IR spectroscopy by using carbon monoxide (CO) as a molecular probe. In the literature, it is reported that strongly unsaturated cationic Ti sites (Lewis acid), which are important for reactivity, should cause a large upshift of the CO stretching frequency. By using IR spectroscopy of CO on TiO2 nanomaterials and theoretical analyses, here this model is challenged. It is shown that the stretching frequency of adsorbed CO results from a facet-dependent and synergic CO-surface donation (upshift) - surface-CO backdonation (downshift) mechanism. These results imply that the interaction of adsorbed molecules with the Ti centers is tuned by the surface oxygen atoms of the first coordination sphere, which play an active role as indirect electron density donors (Lewis base). PMID- 27003516 TI - Development of Glucose Regulated Protein 94-Selective Inhibitors Based on the BnIm and Radamide Scaffold. AB - Glucose regulated protein 94 (Grp94) is the endoplasmic reticulum resident of the heat shock protein 90 kDa (Hsp90) family of molecular chaperones. Grp94 associates with many proteins involved in cell adhesion and signaling, including integrins, Toll-like receptors, immunoglobulins, and mutant myocilin. Grp94 has been implicated as a target for several therapeutic areas including glaucoma, cancer metastasis, and multiple myeloma. While 85% identical to other Hsp90 isoforms, the N-terminal ATP-binding site of Grp94 possesses a unique hydrophobic pocket that was used to design isoform-selective inhibitors. Incorporation of a cis-amide bioisostere into the radamide scaffold led to development of the original Grp94-selective inhibitor, BnIm. Structure-activity relationship studies have now been performed on the aryl side chain of BnIm, which resulted in improved analogues that exhibit better potency and selectivity for Grp94. These analogues also manifest superior antimigratory activity in a metastasis model as well as enhanced mutant myocilin degradation in a glaucoma model compared to BnIm. PMID- 27003520 TI - [Not Available]. PMID- 27003519 TI - Serum nitrate and NOx levels in preeclampsia are higher than in normal pregnancy. AB - OBJECTIVES: To compare nitric oxide (NO) serum levels in women with and without preeclampsia. METHODS: 106 women were classified into preeclampsia group (n = 40) and normotensive group (n = 66). NO content was measured in the serum. Clinical and laboratorial data were recorded for comparison. RESULTS: Preeclampsia presented a significant increase in nitrate and NOx levels compared to the control group. Uric acid, gestational age, systolic and diastolic blood pressure, and creatinine showed correlation with nitrates and NOx. CONCLUSION: Increase of NO was observed in preeclampsia women. Failure in the mechanism of action, dependent on cyclic GMP, may justify this finding. PMID- 27003521 TI - [Not Available]. AB - Shoulder dislocations are not rare in a radiology department working with emergency radiology. The majority are anteriorly dislocated and easy to diagnose. The posteriorly dislocated shoulders are more rare and often more difficult to spot on plain X-ray films. This case report describes a very rare condition with bilateral posterior fracture dislocations in a healthy man following generalized seizures of unknown cause. In spite of complaints of discomfort in the shoulders, two days passed by before the shoulder dislocations were diagnosed. PMID- 27003522 TI - [Not Available]. AB - For the most severely injured and unstable patients physician staffed second tier emergency medical service (EMS) units are used in many European areas. Physician staffed prehospital care is associated with a high rate of survival, advanced trauma care and beneficial cost-effectiveness. In the Nordic countries anaesthesiologists staff the rapid response cars and ambulance helicopters. This article reviews the current status of physician EMS in Sweden and the rapid development of new prehospital intensive care methods. PMID- 27003523 TI - [Not Available]. AB - Hyponatremia is the most frequent electrolyte abnormality seen postoperatively in pediatric patients receiving maintenance fluid therapy. Hyponatremia is also common in acute pediatric illness. The main factors contributing to hyponatremia in these conditions are increased secretion of antidiuretic hormone (ADH) and routine use of sodium hypotonic fluids. An increased ADH secretion results in an impaired ability to excrete free water. If the sodium concentration falls to less than 125 mmol/L hyponatremic encephalopathy might develop, resulting in cerebral edema. This is avoided if hypotonic maintenance fluids are not used perioperatively or for rehydration or maintenance during acute critical illness in children. PMID- 27003524 TI - [Not Available]. PMID- 27003525 TI - [Not Available]. AB - There are three main points (guidelines, patient safety and taboo of suicide) in the article. Guidelines for meeting suicidal patients presented by the Aeschi group are now available. These are based on the psychology of suicidality and are in line with the issue of client-centeredness in health care. To view suicidality as a patient safety issue also means that suicidal acts can be understood as a form of accident. The taboo of suicide has decreased, which has opened new doors for research. PMID- 27003526 TI - [The pediatrician who renewed poetry assisted over 3,000 women during delivery]. PMID- 27003527 TI - [Use the right method to prove sobriety in driver's license issues]. PMID- 27003528 TI - [Not Available]. PMID- 27003529 TI - ["Medical Child Abuse" lack scientific basis]. PMID- 27003530 TI - [Uterus transplantation in Sweden - the 5 first children in the world born. Promising results - all the children are healthy]. PMID- 27003531 TI - [Indicators and let down patients]. PMID- 27003532 TI - [Not Available]. PMID- 27003533 TI - [Merits and transparency]. PMID- 27003534 TI - [The national audit office and CBT]. PMID- 27003535 TI - [New whooping cough deaths]. PMID- 27003536 TI - [The waiting time for internship is a bottleneck - the government should take over the responsibility]. PMID- 27003537 TI - [The faculties should review the requirements for professional medical ethicists]. PMID- 27003538 TI - [Reply from The Society of Women Physicians: Surrogacy is not about the children but about the adults]. PMID- 27003539 TI - [Not Available]. PMID- 27003540 TI - [Uterus transplantation requires ethical consideration. Research progress does not automatically call for routine medical care]. PMID- 27003541 TI - [Not Available]. PMID- 27003542 TI - [Not Available]. PMID- 27003543 TI - [Reply to Victor Madsen: It is up to the Ministry of Education]. PMID- 27003544 TI - A new insight into the conformation and melt dynamics of hydrogenated polybutadiene as revealed by computer simulations. AB - Extensive molecular dynamics simulations of the macromolecular conformation and the melt dynamics for model polymers of different molecular weights have been carried out. The selected models are hydrogenated polybutadienes with a 2% content of ethyl branches and linear polyethylene. It will be shown that the density and chain stiffness are clearly affected by both the molecular weight and the presence of ethyl branches. Furthermore, the results obtained from the simulations on the molecular size and, more remarkably, chain dynamics, perfectly match the neutron scattering experiments performed by Zamponi et al. in hydrogenated polybutadienes. We observe a clear chain contraction and a slow dynamics for the hydrogenated polybutadiene with respect to the linear chain of the same molecular length. Using the Likhtman-McLeish definitions, the obtained values of the entanglement relaxation time (taue) and the tube diameter (a) are found to be in agreement with the available experimental data (by rheology and neutron spin echo) as well as with those obtained by the simulations. Finally, a very good agreement of diffusion coefficients as a function of the molecular weight between simulations and experiments is observed. Therefore, there exists a clear difference between the results obtained for branched and linear polyethylene, accounting for a definitive effect of the short chain branching on the conformational properties and the melt dynamics of polyolefins. PMID- 27003546 TI - Behavioural evidence for separate mechanisms of audiovisual temporal binding as a function of leading sensory modality. AB - The ability to integrate auditory and visual information is critical for effective perception and interaction with the environment, and is thought to be abnormal in some clinical populations. Several studies have investigated the time window over which audiovisual events are integrated, also called the temporal binding window, and revealed asymmetries depending on the order of audiovisual input (i.e. the leading sense). When judging audiovisual simultaneity, the binding window appears narrower and non-malleable for auditory-leading stimulus pairs and wider and trainable for visual-leading pairs. Here we specifically examined the level of independence of binding mechanisms when auditory-before visual vs. visual-before-auditory input is bound. Three groups of healthy participants practiced audiovisual simultaneity detection with feedback, selectively training on auditory-leading stimulus pairs (group 1), visual-leading stimulus pairs (group 2) or both (group 3). Subsequently, we tested for learning transfer (crossover) from trained stimulus pairs to non-trained pairs with opposite audiovisual input. Our data confirmed the known asymmetry in size and trainability for auditory-visual vs. visual-auditory binding windows. More importantly, practicing one type of audiovisual integration (e.g. auditory visual) did not affect the other type (e.g. visual-auditory), even if trainable by within-condition practice. Together, these results provide crucial evidence that audiovisual temporal binding for auditory-leading vs. visual-leading stimulus pairs are independent, possibly tapping into different circuits for audiovisual integration due to engagement of different multisensory sampling mechanisms depending on leading sense. Our results have implications for informing the study of multisensory interactions in healthy participants and clinical populations with dysfunctional multisensory integration. PMID- 27003547 TI - Using Certification to Promote Uptake of Real-World Evidence by Payers. AB - Most randomized controlled trials are unable to generate information about a product's real-world effectiveness. Therefore, payers use real-world evidence (RWE) generated in observational studies to make decisions regarding formulary inclusion and coverage. While some payers generate their own RWE, most cautiously rely on RWE produced by manufacturers who have a strong financial interest in obtaining coverage for their products. We propose a process by which an independent body would certify observational studies as generating valid and unbiased estimates of the effectiveness of the intervention under consideration. This proposed process includes (a) establishing transparent criteria for assessment, (b) implementing a process for receipt and review of observational study protocols from interested parties, (c) reviewing the submitted protocol and requesting any necessary revisions, (d) reviewing the study results, (e) assigning a certification status to the submitted evidence, and (f) communicating the certification status to all who seek to use this evidence for decision making. Accrediting organizations such as the National Center for Quality Assurance and the Joint Commission have comparable goals of providing assurance about quality to those who look to their accreditation results. Although we recognize potential barriers, including a slowing of evidence generation and costs, we anticipate that processes can be streamlined, such as when familiar methods or familiar datasets are used. The financial backing for such activities remains uncertain, as does identification of organizations that might serve this certification function. We suggest that the rigor and transparency that will be required with such a process, and the unassailable evidence that it will produce, will be valuable to decision makers. PMID- 27003548 TI - Challenges for Managed Care from 340B Contract Pharmacies. AB - The federal 340B Drug Pricing Program has expanded rapidly, with important yet still unmeasured impact on both managed care practice and policies. Notably, providers increasingly rely on external, contract pharmacies to extend 340B pricing to a broad set of patients. In 2014, 1 in 4 U.S. retail, mail, and specialty pharmacy locations acted as contract pharmacies for 340B-covered entities. This commentary discusses crucial ways in which 340B growth is affecting managed care pharmacy through formulary rebates, profits from managed care paid prescriptions, disruption of retail pharmacy networks, and reduced generic dispensing rates. Managed care should become more engaged in the discussion on how the 340B program should evolve and offer policy proposals to mitigate the challenges being encountered. There is also an urgent need for objective, transparent research on the 340B program's costs, benefits, and implications for managed care pharmacy and practice. PMID- 27003549 TI - Using an Electronic Medication Refill System to Improve Provider Productivity in an Accountable Care Setting. AB - BACKGROUND: Even within fully integrated health care systems, primary care providers (PCPs) often lack support for medication management. Because challenges with conducting medication reconciliation, improving adherence, and achieving optimal patient outcomes continue to be prevalent nationally, it is critical that PCPs are provided the resources and support they need to provide high-quality, patient-centered care in an accountable care environment. PROGRAM DESCRIPTION: Sharp Rees-Stealy Medical Group uses a fully electronic medication refill system that allows for a centralized team to manage all incoming requests. Over time, 16 disease-specific protocols were created that allowed the pharmacy team to absorb approximately 80% of incoming refill requests for all enrolled PCPs. The refill clinic assessed all clinic information that a PCP would normally review in order to approve a refill. Tasks performed by the clinical pharmacists included medication reconciliation, dosage adjustment, and coordination of distribution from external mail order and retail pharmacies. OBSERVATIONS: In 2014, the number of tasks related to refill management reviewed by the refill/medication therapy management service totaled 302,592, resulting in 140,350 refill authorizations and multiple interventions related to medication use. Physicians have estimated that the service provides between 20 and 30 minutes of time savings per day. Assuming an annual PCP salary of around $200,000, 20 to 30 minutes per day would amount to $33 to $50 saved per day per physician. The savings is even higher when time savings from other clinical staff is included. IMPLICATIONS: The development of this electronic medication refill service has provided the following important lessons: (a) organizations rely on a leader or champion to push through process reforms--this program started with reluctant physicians first to determine best practices; (b) the lack of clinical pharmacist profiles within electronic health records (EHR) is a serious concern, since the creation of these profiles may not be easy or timely; and (c) PCPs working within an EHR environment will quickly embrace the idea of a service that can save them up to 30 minutes per day. With PCPs continuing to take on additional population health management tasks in accountable care organizations, pharmacists can provide workload offsets by meaningfully contributing to medication-related care. PMID- 27003550 TI - Primary Nonadherence, Associated Clinical Outcomes, and Health Care Resource Use Among Patients with Rheumatoid Arthritis Prescribed Treatment with Injectable Biologic Disease-Modifying Antirheumatic Drugs. AB - BACKGROUND: Adherence to biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with rheumatoid arthritis (RA) is often suboptimal in routine clinical practice. Low or nonadherence can reduce the effectiveness of bDMARD therapies. OBJECTIVE: To evaluate filling of newly prescribed initial bDMARDs for the treatment of RA and evaluate potential for characterizing treatment decisions and patient outcomes. METHODS: In this retrospective cohort analysis, patients aged >= 18 years with an RA diagnosis (ICD-9-CM code 714.xx) were selected from a de-identified database of clinical information from the Electronic Health Record (EHR; Humedica) database linked to health care claims (Optum) from commercial and Medicare Advantage health plans (2007-2013). The first biologic prescription date in EHR was the index date. Patients were categorized as filling the prescription within 30 days (early fillers), 31-180 days (late fillers), or not at all within 180 days (nonfillers) of index date. RESULTS: Of 373 patients meeting inclusion criteria, 170 (45.6%), 59 (15.8%), and 144 (38.6%) were categorized as early fillers, late fillers, and nonfillers, respectively. Most prescriptions were written or ordered for tumor necrosis factor inhibitors (88.7%). Compared with late and nonfillers, early fillers were younger and more likely to be female, with higher pain scores (among those reporting pain scores) and RA severity scores pre-index, and filled more prescriptions for any reason pre-index. More nonfillers (66.0%) were Medicare patients than early (17.7%) and late (35.6%) fillers. During days 0-30 post-index, conventional synthetic DMARD use was greatest for early fillers (45.9%) and lowest among nonfillers (24.3%); however, during days 31-180 post-index, the proportion was highest for late fillers (61.0%) and lowest for nonfillers (35.4%). Of early fillers, 12.9% did not fill/receive a bDMARD after 30 days. Only 23 patients had pre/post-index pain scores, and 47 patients had a rationale for stopping or not filling a bDMARD. In patients with pharmacy and medical coverage for 180 days post-index, early fillers had greater RA-related pharmacy and medical resource use and costs than late and nonfillers combined. CONCLUSIONS: These findings confirm a high rate of primary nonadherence to bDMARDs among patients with RA. PMID- 27003551 TI - Patterns of Care in Patients with Metastatic Renal Cell Carcinoma Among a U.S. Payer Population with Commercial or Medicare Advantage Membership. AB - BACKGROUND: Several systemic therapies are now approved for first- and second line treatment of metastatic renal cell carcinoma (mRCC). Although the National Comprehensive Cancer Network (NCCN) guidelines offer physicians evidence-based recommendations for therapy, there are few real-world studies to help inform the utilization of these agents in clinical practice. OBJECTIVES: To (a) describe the patterns of use associated with systemic therapies for mRCC among Humana members in the United States diagnosed with mRCC, (b) assess consistency with the NCCN guidelines for treatment, and (c) to describe the initial first-line therapy regimen by prescriber specialty and site of care. METHODS: This was a retrospective study using Humana's claims database of commercially insured patients and patients insured by the Medicare Advantage Prescription Drug plan. The study period was from January 1, 2007, to December 31, 2013. Patients with mRCC were identified by ICD-9-CM codes 189.0/189.1 and 196.xx to 199.xx; all patients were between 18 and 89 years of age, had received systemic therapy for their disease, and were followed up for 180 days. Outcome measures included choice of initial systemic therapy, starting and ending doses, first-line treatment persistence and compliance, and choice of second-line therapy. Persistence was measured using time to discontinuation of first-line therapy and proportion of days covered (PDC; the ratio of [total days of drug available minus days of supply of last prescription] to [last prescription date minus first prescription date]). Compliance was measured using the medication possession ratio (MPR; the ratio of [total days supply minus days supply of last prescription] to [last prescription date minus first prescription date]). RESULTS: A total of 649 patients met all inclusion criteria; 109 were insured by commercial plans and 540 were insured by Medicare. The mean +/- SD age of patients was 68.6 +/- 9.4 years, and 68.6% were male; Medicare patients were older than commercial patients (71.7 +/- 7.4 vs. 56.6 +/- 9.1 years, respectively; P < 0.001). The most common comorbidities among the patient population were hypertension, hyperlipidemia, diabetes, and heart disease. The majority of patients (68.6%) received an oral tyrosine kinase inhibitor (TKI) as their first line of therapy: 43.9% received sunitinib, 14.0% received sorafenib, 10.0% received pazopanib, and 0.6% received axitinib. Mean +/- SD time to discontinuation of first-line TKI treatment was 169.1 +/- 29.5 days with sunitinib, 160.3 +/- 41.1 days with pazopanib, and 160.1 +/- 41.4 days with sorafenib. Other first-line therapies included inhibitors of mammalian target of rapamycin (mTOR) (19.7%) and the antivascular endothelial growth factor agent bevacizumab (9.4%). Among patients receiving mTOR inhibitors, 14.8% were started on temsirolimus and 4.9% were started on everolimus. The median starting and ending doses were the same for each drug except for sunitinib. Mean +/- SD times to discontinuation of temsirolimus, everolimus, and bevacizumab were 171.8 +/- 26.2, 137.0 +/- 62.2, and 150.8 +/- 56.0 days, respectively. Persistence on first line regimen as measured by PDC was high (PDC >= 80%) for 89% of oral therapies and 77% of injectable therapies; first-line compliance was high (MPR >= 80%) for 77% of oral therapies and 68% of injectables. Among patients who received second line therapy, the most common regimen was everolimus (29.2%), followed by bevacizumab (19.8%), temsirolimus (15.6%), and sunitinib (13.6%). Specialty codes obtained from the database provider identified internal medicine specialists and oncologists as the most common prescribers of TKIs and mTOR inhibitors. CONCLUSIONS: Patterns of use were similar for each of the prescribed systemic treatments for mRCC, and the majority of patients were highly persistent and compliant with first-line therapies. Time to treatment discontinuation was slightly longer with oral agents compared with injectable drugs. PMID- 27003552 TI - Factors Associated with Adherence Rates for Oral and Intravenous Anticancer Therapy in Commercially Insured Patients with Metastatic Colon Cancer. AB - BACKGROUND: Over the past decade, oncology therapies have trended toward orally administered regimens, and there has been growing attention on evaluation of factors that affect adherence. There has not been a rigorous investigation of factors associated with adherence to intravenous (i.v.) and oral anticancer drugs in the setting of metastatic colorectal cancer (mCRC). OBJECTIVES: To (a) assess potential patient-specific factors related to adherence to mCRC chemotherapy regimens and (b) compare adherence with IV versus oral dosage forms. METHODS: A retrospective analysis was performed using the Optum Oncology Management claims database. Patients aged 18 years and older diagnosed with mCRC between July 1, 2004, and December 31, 2010, who were insured by a commercial health plan were included in the study. Adherence to i.v. and oral chemotherapy regimens was assessed using the National Comprehensive Cancer Network (NCCN) guidelines as the standard for expected cycle/regimen duration. The most commonly prescribed chemotherapy regimens were assessed. Adherence was evaluated using the medication possession ratio (MPR), calculated as the number of days a patient was covered by their chemotherapy regimen, according to NCCN guidelines, divided by the number of days elapsed from the first to the last infusion of that regimen. For most analyses, the MPR was considered a continuous variable that could take on values between 0 and 1. In other analyses, a dichotomous categorical variable designated if the MPR was at least 0.8 versus less than 0.8. The Wilcoxon rank sum, Kruskal Wallis, and Student's t-test were used to detect differences in continuous measures between patients receiving oral capecitabine therapy versus i.v. chemotherapy. The chi square test (X(2) test) or Fisher's exact test was used to assess differences in the dichotomous MPR variable. Generalized estimating equation (GEE) models were used for regimen-level analyses to account for correlated responses within individuals. RESULTS: A total of 6,780 patients were included in the analysis, virtually all (98%) with commercial insurance coverage and the remaining (2%) with Medicare Advantage. Patients with mCRC received 17,095 regimens of chemotherapy, including 2,252 regimens of oral capecitabine. Of the 17,095 regimens, 6,780 (40%) were first-line regimens (i.e., the first time mCRC was treated for a given patient). The most common chemotherapy regimen, regardless of line of therapy, was FOLFOX (2,991 regimens, 17.5% of all regimens used). FOLFOX-based therapies with or without bevacizumab were the most common regimens for first- and second-line chemotherapy, while oral capecitabine treatment was the most commonly prescribed regimen for patients in third- or fourth-line therapy. Overall, medication adherence across all regimens was relatively high, with a mean MPR of 0.87 (SD = 0.17). Evaluation of the distribution of i.v. and oral capecitabine regimens revealed that 28% of all regimens were associated with an MPR of less than 0.8. The average MPR was clinically similar, but statistically higher for i.v. chemotherapy regimens (0.881) compared with oral capecitabine regimens (0.799; P < 0.0001). In the multivariable GEE model, lung or liver metastases were associated with a higher MPR, while lower Charlson Comorbidity Index and oral anticancer therapy were associated with lower MPR. Furthermore, as line of therapy increased, the difference in MPR between patients receiving oral capecitabine and i.v. chemotherapy increased. CONCLUSIONS: This analysis determined that adherence with i.v. chemotherapy regimens was clinically similar, but statistically higher, compared to oral capecitabine therapy. The difference in adherence rates between the 2 routes of administration increased as the line of anticancer regimen increased. These results suggest that there should be an increased focus on improving adherence rates in patients receiving oral capecitabine. PMID- 27003553 TI - The Burden of Opioid-Induced Constipation: Discordance Between Patient and Health Care Provider Reports. AB - BACKGROUND: Opioid-induced constipation (OIC), a common side effect of opioid treatment for chronic pain, affects patient health-related quality of life (HRQL) and may prompt some patients to lower the dose or alter adherence to their opioid medication, compromising pain relief. Although health care providers (HCPs) are aware of the potential for OIC, patients may not inform their HCPs of their OIC symptoms, and HCPs may not initiate conversation regarding OIC if their patients' pain is controlled. Patients often try to address OIC symptoms on their own by using natural approaches or over-the-counter options. When OIC is discussed in an office visit, HCPs typically recommend conventional laxatives to relieve symptoms, but the efficacy of this approach is unproven and often suboptimal. In many areas of medicine, HCP perceptions of the impact of adverse effects of treatment on a patient's HRQL do not align with the patient's experience. OBJECTIVES: To (a) describe HCP-reported understanding of his or her patients' experiences with OIC and (b) evaluate the level of agreement or discordance in perception between patients and their HCPs of OIC's impact on clinical outcomes. METHODS: This was a prospective, longitudinal, observational cohort study conducted in the United States, Canada, Germany, and the United Kingdom (NCT01928953) in patients aged 18 to 85 years who had been receiving daily opioid therapy for >= 4 weeks for chronic noncancer pain with presence of OIC in the past 2 weeks. Data were collected from retrospective chart reviews, HCP questionnaires, and web-based patient surveys. Eligible patients enrolled online and completed the Patient Assessment of Constipation-Symptoms, the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem, the EuroQOL 5 Dimensions, and the Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue standardized questionnaires. The patient-reported component included 1 baseline survey and 8 follow-up surveys over 24 weeks. HCPs completed a web-based survey at baseline and at week 24 to assess their perceptions of OIC burden, treatment patterns, laxative use, and overall treatment satisfaction. The correspondence of patient- and HCP-reported data was evaluated for all similar outcomes from these 2 databases. RESULTS: Patients (N = 489) reported a mean (SD) number of bowel movements (BMs) per week and spontaneous BMs per week of 3.7 (2.9) and 1.4 (2.3), respectively, at baseline. Most (87%) reported chronic pain of >= 2 years duration; 65% had used opioids for >= 2 years; and the mean pain score at baseline was 6.3, consistent with a moderate-to-severe pain population. Most (97%) patients at baseline reported any gastrointestinal-related symptom of at least moderate intensity, with 82% reporting the same intensity of any symptom at week 24. Of the 405 patients who had seen their HCPs in the past month, 63% reported that they had spoken to their HCPs about constipation, and 62% reported that their HCPs had asked them if they had constipation in the past month. The proportion of agreement between HCPs and their patients on the presence of constipation at baseline was 61%. Similar average pain ratings between HCPs and patients (5.9 vs. 6.0) at week 24 suggested clear communication regarding the level of pain experienced by the patient; however, OIC symptoms, laxative use and effectiveness, and impact of OIC on pain management and HRQL were not fully appreciated by HCPs. CONCLUSIONS: The importance and severity of OIC are perceived differently by patients and their HCPs, a discordance that complicates pain management and demonstrates a need for greater communication. These disparate perceptions indicate a need for clinical education and coordination of care by HCPs to improve understanding and proactively manage OIC in patients with chronic noncancer pain. PMID- 27003554 TI - Satisfaction with Therapy Among Patients with Chronic Noncancer Pain with Opioid Induced Constipation. AB - BACKGROUND: Greater satisfaction with medication is associated with better adherence; however, specific to opioid-induced constipation (OIC), data on the relationship between medication satisfaction and efficacy are lacking. OBJECTIVE: To understand satisfaction with therapy among patients with chronic noncancer pain and OIC. METHODS: A prospective longitudinal study was conducted in the United States, Canada, Germany, and the United Kingdom using web-based patient surveys. Patients on daily opioid therapy for >= 74 weeks for the treatment of chronic noncancer pain with OIC were recruited from physician offices and completed a web-based survey at baseline and weeks 2, 4, 6, 8, 12, 16, 20, and 24. When completing each survey, patients selected the remedies used in the previous 2 weeks to relieve constipation; options included natural/behavioral therapies, over-the-counter (OTC) therapies, and prescription laxatives. Patients selected the amount of relief and satisfaction with each selected therapy. Descriptive statistics were calculated; Spearman's correlations were calculated for symptom relief and satisfaction. RESULTS: Mean age of the 489 patients who met the criteria for OIC and completed the baseline survey was 52.6 +/- 11.6 years; 62% were female; 85% were white. Increasing levels of relief from constipation were associated with increasing levels of satisfaction for all agents; correlations were > 0.55 and statistically significant (P < 0.001). Among the patients who had used OTC therapies in the 2 weeks prior to baseline, 54% to 73% reported that they were somewhat or very satisfied with the therapy. Yet, of these satisfied patients, 28% to 63% experienced no or only slight relief from the therapy. Twenty percent to 79% of the patients who had used prescription laxatives in the 2 weeks prior to baseline reported being at least somewhat satisfied with the therapy. CONCLUSIONS: These results indicate that there is a high rate of inadequate response to laxatives for patients with OIC that persisted for the 6 months of this study. While increased relief from constipation was associated with increased satisfaction for all therapies, there remains a substantial number of patients who report satisfaction despite having only inadequate relief from OIC that merits further investigation. PMID- 27003555 TI - Patient Adherence to Olmesartan/Amlodipine Combinations: Fixed Versus Extemporaneous Combinations. AB - BACKGROUND: Lack of adherence to prescribed therapies is often a cause of suboptimal blood pressure control in patients with hypertension. To enhance patients' adherence to treatment, fixed-dose combinations of active substances with complementary mechanisms of action have been developed. An angiotensin converting enzyme inhibitor or an angiotensin receptor blocker (ARB) is often combined with a calcium channel blocker. Olmesartan is the most used ARB in combination therapy. In Italy, in September 2011, a fixed-dose combination of olmesartan/amlodipine (olmesartan/amlodipine 20/5 mg, 40/5 mg, or 40/10 mg) was introduced to treat patients with hypertension for whom control of blood pressure is not reached with either olmesartan or amlodipine alone. Prior research on adherence to olmesartan/amlodipine combinations was carried out in local contexts (e.g., claims databases of Italian regions or local health authorities), and/or it was limited by the fact that adherence was assessed against monotherapies already known for their low compliance profile, such as diuretics. OBJECTIVE: To compare adherence with olmesartan/amlodipine fixed-dose combination (FDC) and extemporaneous combination in primary care in Italy. METHODS: A nationwide, population-based study was conducted by using the Health Search IMS Health Longitudinal Patient Database. Patients aged > 17 years, affected by hypertension and treated with the FDC or extemporaneous combination of olmesartan/amlodipine, were identified. Adherence to these 2 therapeutic regimens was estimated by calculating the proportion of days covered (PDC). Patients were classified into 3 levels of adherence: high (PDC >= 80%), intermediate (PDC = 40%-79%), or low (PDC < 40%). RESULTS: In the 6-month follow-up, FDC showed higher adherence compared with an extemporaneous combination (55.1% vs. 15.9%, P < 0.001). This difference was confirmed in a multivariable logistic regression model clustered on patient identifier (odds ratio = 6.65; 95% CI = 3.10-14.26; P < 0.001). The proportion of patients adherent to FDC varied from 60.4% for the 40/5 mg formulation to 47.5% for the 40/10 mg formulation. CONCLUSIONS: These findings suggest that higher adherence may be achieved with FDCs than with extemporaneous combinations. To improve the degree of adherence, general practitioners may consider prescribing fixed combinations of antihypertensive agents as soon as monotherapies fail to achieve the expected therapeutic objective. PMID- 27003556 TI - Treatment Patterns Associated with ACR-Recommended Medications in the Management of Fibromyalgia in the United States. AB - BACKGROUND: Fibromyalgia (FM) affects up to 6% of U.S. adults, resulting in a significant burden on the health care system and poor quality of life for patients. Duloxetine, pregabalin, and milnacipran are approved for management of FM; however, consensus is lacking regarding optimal therapy. Patients with FM taking approved medications often do not experience meaningful symptom relief, and many experience intolerable adverse events. OBJECTIVE: To assess treatment patterns associated with available and commonly used medications for the management of FM using U.S. health insurance claims. METHODS: This retrospective analysis used the MarketScan claims database to identify adults with a first diagnosis of FM (ICD-9-CM code 729.1) between 2009 and 2011 with continuous health plan enrollment for 12 months pre- and post-index. Medications of interest were pregabalin, gabapentin, duloxetine, milnacipran, cyclobenzaprine, and tramadol. These are 6 of the 8 medications recommended by the American College of Rheumatology (ACR) for treating FM; the other 2 (amitriptyline and venlafaxine) were only included in some initial assessments. The Charlson Comorbidity Index (CCI) was used to assess overall comorbidity burden. Endpoints included proportion of patients treated within 1 year after first diagnosis; initial treatment pattern; adherence over the first-year follow-up period for the medications of interest; and discontinuation, switching, and combination therapy patterns among pain medications of interest at different time points. Proportion of days covered (PDC; defined as number of days in the period when the patient had drug supply divided by the number of days in the period) was used to define adherence, which was categorized as low (PDC < 50%), medium (PDC 50% to < 80%), or high (PDC >= 80%). The time to discontinuation (defined as the first drug supply gap >= 90 days) was estimated using Kaplan-Meier analysis. RESULTS: Overall, 240,144 patients met the inclusion criteria. Patients were predominantly women (68%), had preferred provider organization insurance coverage (68%), and had a CCI score < 1 at baseline (69%). Only 31% (n = 74,738) initiated a treatment with a prescription medication listed in the ACR guidelines, and many patients received less than the recommended dose. Most (n = 70,919) patients initially received monotherapy with one of the 8 prescription medications. Of those who started with >= 2 medications (n = 3,819), cyclobenzaprine plus tramadol was the most frequent combination. Adherence was suboptimal for all 6 medications of interest. Duloxetine had the highest mean PDC (59%); for all other agents, mean PDC was < 50%. With the exception of duloxetine, discontinuation rates at 6 months were > 50% for all agents. Alterations in therapy were common. Among patients who discontinued their initial treatment of duloxetine, pregabalin, or milnacipran, approximately one-third had switched treatments within 90 days after their first prescription. For those who maintained their initial treatment agent, approximately 50% of patients added a second pain medication within 1 year of treatment initiation. CONCLUSIONS: The evidence suggests that patients with FM often do not receive 1 of the prescription medications recommended by ACR guidelines, and those who do are commonly prescribed lower-than-recommended doses, potentially resulting in poor effectiveness and tolerability. Discontinuation, switching, and addition of new pain medications are common, which may indicate low levels of satisfaction with initial treatment. New therapies with improved effectiveness and better tolerability are urgently needed for patients with FM. PMID- 27003557 TI - Use of Add-on Treatment to Metformin Monotherapy for Patients with Type 2 Diabetes and Suboptimal Glycemic Control: A U.S. Database Study. AB - BACKGROUND: The American Diabetes Association (ADA) recommends metformin to treat individuals diagnosed with type 2 diabetes and recommends that hemoglobin A1c (HbA1c) be maintained below or around 7%. If the HbA1c target is not achieved or maintained by metformin monotherapy at maximal tolerated dose over 3 to 6 months, treatment modification with addition of a second oral antihyperglycemic agent or by initiating insulin is recommended. Despite the importance of attaining and maintaining HbA1c goals, actual treatment behavior may not follow ADA guidelines to add a second oral agent or to initiate insulin as expected even considering that individual patient's needs are taken into account when treatment decisions are made. OBJECTIVE: To evaluate treatment addition for metformin monotherapy users with suboptimal glycemic control and associated factors. METHODS: A retrospective health care claims study identified 7,109 subjects aged 18 to 89 years, treated for type 2 diabetes with an HbA1c > 7% following at least 60 days of continuous metformin monotherapy. Subjects were required to have 12 months continuous enrollment with the health plan before and after the index lab date. Pharmacological treatment additions after the HbA1c lab result and time to treatment addition were evaluated. A logistic regression model was used to evaluate the patient characteristics and comorbidities associated with the treatment addition. RESULTS: Thirty-eight percent of study subjects had evidence of addition of a second antidiabetic medication to primary metformin monotherapy, 57.5% remained on metformin monotherapy, and 4.5% discontinued metformin altogether. A logistic regression model found age inversely related to treatment addition: age 45-64 versus 18-44 (OR = 0.77, 95% CI = 0.59-0.99) and age 65-89 versus 18-44 (OR = 0.57, 95% CI = 0.43-0.74). HbA1c was positively related to treatment addition: > 8%-9% versus > 7%-8% (OR = 2.31, 95% CI = 2.00-2.67); > 9% 10% versus > 7%-8% (OR = 2.88, 95% CI = 2.32-3.58); and > 10% versus > 7%-8% (OR = 3.54, 95% CI = 2.92-4.28). Evidence of ophthalmic disorder was not related to treatment addition (P = 0.056), but evidence of hypertension (OR = 1.56, 95% CI = 1.28-1.89); hyperlipidemia (OR = 1.28, 95% CI = 1.05-1.55); other cardiovascular diseases (OR = 1.30, 95% CI = 1.16-1.45); obesity (OR = 1.21, 95% CI = 1.08 1.36); and renal disease (OR = 1.35, 95% CI = 1.21-1.51) were associated. CONCLUSIONS: The majority of the metformin monotherapy users with suboptimal glycemic control did not initiate add-on therapy as recommended by guidelines, and prolonged time on metformin monotherapy demonstrated clinical inertia in real world clinical practice. Several factors were associated with this delay including older age, lower index HbA1c, and lack of evidence of certain comorbidities. PMID- 27003558 TI - Evaluating the Initiation of Novel Oral Anticoagulants in Medicare Beneficiaries. AB - BACKGROUND: As alternatives to warfarin, 2 novel oral anticoagulants (NOACs), dabigatran and rivaroxaban, were approved in 2010 and 2011 to prevent stroke and other thromboembolic events in patients with atrial fibrillation. It is unclear how patient characteristics are associated with the initiation of anticoagulants. OBJECTIVE: To evaluate how patient demographics, clinical characteristics, types of insurance, and patient out-of-pocket spending affect the initiation of warfarin and 2 NOACs--dabigatran and rivaroxaban. METHODS: We used pharmacy claims data from a 5% random sample of Medicare beneficiaries to identify patients who were newly diagnosed with atrial fibrillation between October 1, 2010, and October 31, 2012, and who were prescribed an oral anticoagulant within 60 days of diagnosis. We identified key predictors of initiation of NOACs using a multinomial logistic regression model with generalized logit link. RESULTS: Patients who were black and who had a history of acute myocardial infarction, stroke or transient ischemic attack, chronic kidney disease, or congestive heart failure were significantly associated with lower odds of receiving NOACs compared with warfarin. Age greater than 65 years, a history of hypertension, and use of nonsteroidal anti-inflammatory drugs were positively associated with the initiation of NOACs. Rivaroxaban was most likely to be initiated among women, followed by warfarin and dabigatran. Individuals receiving a low-income subsidy were more likely to initiate warfarin than NOACs, even though they paid little copayment. Individuals with supplemental Part D drug coverage, such as national Programs for All-Inclusive Care for the Elderly or employer-sponsored plans, were more likely to initiate NOACs compared with warfarin. CONCLUSIONS: We found that race, sex, type of Part D plans, and some clinical conditions were associated with the initiation of NOACs relative to warfarin. But patient demographic and clinical characteristics did not appear to affect which particular NOAC patients initiated. PMID- 27003559 TI - Health Care Utilization and Costs After Initiating Budesonide/Formoterol Combination or Fluticasone/Salmeterol Combination Among COPD Patients New to ICS/LABA Treatment. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects approximately 15 million people in the United States and accounts for approximately $36 billion in economic burden, primarily due to medical costs. To address the increasing clinical and economic burden, the Global Initiative for Chronic Obstructive Lung Disease emphasizes the use of therapies that help prevent COPD exacerbations, including inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA). OBJECTIVE: To evaluate health care costs and utilization among COPD patients newly initiating ICS/LABA combination therapy with budesonide/formoterol (BFC) or fluticasone/salmeterol (FSC) in a managed care system. METHODS: COPD patients aged 40 years and older who initiated BFC (160/4.5 MUg) or FSC (250/50 MUg) treatment between March 1, 2009, and March 31, 2012, were identified using claims data from major U.S. health plans. BFC and FSC patients were propensity score matched (1:1) on age, sex, prior asthma diagnosis, prior COPD-related health care utilization, and respiratory medication use. COPD-related, pneumonia-related, and all-cause costs and utilization were analyzed during the 12-month follow-up period. Post-index costs were assessed with generalized linear models (GLMs) with gamma distribution. Health care utilization data were analyzed via logistic regression (any event vs. none) and GLMs with negative binomial distribution (number of visits) and were adjusted for the analogous pre-index variable as well as pre-index characteristics that remained imbalanced after matching. RESULTS: After matching, each cohort had 3,697 patients balanced on age (mean 64 years), sex (female 52% BFC and 54% FSC), asthma and other comorbid conditions, prior COPD-related health care utilization, and respiratory medication use. During the 12-month follow-up, COPD-related costs averaged $316 less for BFC versus FSC patients ($4,326 vs. $4,846; P = 0.003), reflecting lower inpatient ($966 vs. $1,202; P < 0.001), pharmacy ($1,482 vs. $1,609; P = 0.002), and outpatient/office ($1,378 vs. $1,436; P = 0.048) costs, but higher emergency department ($257 vs. $252; P = 0.033) costs. Pneumonia-related health care costs were also lower on average for BFC patients ($2,855 vs. $3,605; P < 0.001). Similarly, initiating BFC was associated with lower all-use health care costs versus initiating FSC ($21,580 vs. $24,483; P < 0.001, respectively). No differences in health care utilization were found between the 2 groups. CONCLUSIONS: In this study, although no difference was observed in rates of health care utilization, COPD patients initiating BFC treatment incurred lower average COPD-related, pneumonia-related, and all-cause costs versus FSC initiators, which was driven by cumulative differences in inpatient, outpatient, and pharmacy costs. PMID- 27003560 TI - Physician Perception of Patient Medication Adherence in a Cohort of Medicare Advantage Plans in Texas. AB - BACKGROUND: Prescription medication adherence is a known health-related barrier for elderly patients, leading to insufficient disease control and negative health outcomes. The Centers for Medicare & Medicaid Services (CMS) have placed significant emphasis on medication adherence, through the Part D star measures, revolving around treatment for chronic disease states such as hypertension, diabetes, and hyperlipidemia. However, it is unclear if physicians fully grasp the extent of nonadherence within their patient populations with regard to these medications, specifically those patients enrolled in Medicare Advantage Prescription Drug (MA-PD) plans. OBJECTIVES: To (a) determine physicians' perceptions of medication adherence among their patients enrolled in MA-PD plans and (b) compare those perceptions with actual adherence rates obtained from claims data. METHODS: A survey was developed and administered to primary care physicians (PCPs) contracted within a Texas MA-PD plan. The previously validated questionnaire was distributed during an all-PCP quarterly meeting and was collected prior to the meeting's conclusion to increase completion and return rates. PCPs were requested to indicate what percentage of their patients they believed to be adherent to each of the CMS Part D star medication classes, which includes statins, oral antidiabetic drugs (OADs), and reninangiotensin system (RAS) antagonists; what financial category they believe the majority of their patients fall under; and what percentage of their patients receive samples. The PCPs' perceived percentage of adherent patients were compared with the calculated percentage of patients, using a chi-square test at an a priori alpha level of 0.05. The calculated adherence was obtained from pharmacy claims data, meeting the CMS targeted adherence threshold (>= 80%). This adherence rate was calculated using proportion of days covered (PDC) for all 3 medication categories in each PCP's patient population. RESULTS: To compare PCP perception of patient adherence and actual adherence, 226 PCPs were used. The sample population shared similar sex and age distribution with the national physician average; however, there was more racial diversity represented. PCP perception of patient adherence, as well as the actual percentage of adherent patients, were significantly (P < 0.05) different across statins, OADs, and RAS antagonists; lowest perceived percentage, as well as actual percentage, were reported for statins. PCP perception of patient adherence and actual percentage of adherent patients were significantly different in the 3 medication categories. PCPs' correct estimations were significantly (P < 0.0001) lower than expected values, while over- and underestimations were significantly (P < 0.0001) higher than the expected values. CONCLUSIONS: PCPs were almost equally likely to over- or underestimate percentage of adherent patients in their patient pools. PMID- 27003561 TI - A generalized abundance index for seasonal invertebrates. AB - At a time of climate change and major loss of biodiversity, it is important to have efficient tools for monitoring populations. In this context, animal abundance indices play an important role. In producing indices for invertebrates, it is important to account for variation in counts within seasons. Two new methods for describing seasonal variation in invertebrate counts have recently been proposed; one is nonparametric, using generalized additive models, and the other is parametric, based on stopover models. We present a novel generalized abundance index which encompasses both parametric and nonparametric approaches. It is extremely efficient to compute this index due to the use of concentrated likelihood techniques. This has particular relevance for the analysis of data from long-term extensive monitoring schemes with records for many species and sites, for which existing modeling techniques can be prohibitively time consuming. Performance of the index is demonstrated by several applications to UK Butterfly Monitoring Scheme data. We demonstrate the potential for new insights into both phenology and spatial variation in seasonal patterns from parametric modeling and the incorporation of covariate dependence, which is relevant for both monitoring and conservation. Associated R code is available on the journal website. PMID- 27003562 TI - Adrenal Imaging: Magnetic Resonance Imaging and Computed Tomography. AB - The adrenal glands are located superior to the kidneys and play an important role in the endocrine system. Each adrenal gland contains an outer cortex, responsible mainly for the secretion of androgens and corticosteroids, and an inner medulla, which secretes epinephrine and norepinephrine. Here, we review the anatomy of the adrenal glands and explain the current imaging modalities that are most useful for the assessment of the various conditions--both benign and malignant--that can affect these glands. As adrenal lesions are often identified incidentally on cross-sectional imaging performed for other reasons, the management of such adrenal 'incidentalomas' is also discussed. In many cases, adrenal lesions have distinctive imaging features that allow for a full characterization with noninvasive techniques. In some cases, invasive studies such as adrenal vein sampling or adrenal biopsy become necessary. This review should give the reader a wide overview of how various imaging techniques can be useful in the assessment of adrenal pathology. PMID- 27003563 TI - Introduction to Volume 8, Issue 2 of topiCS. PMID- 27003564 TI - "Ready to take on the world": Experiences and understandings of independence after attending residential immersive life skills programs for youth with physical disabilities. AB - STATEMENT OF PURPOSE: Life skills programs aim to equip youth with physical disabilities with the foundational skills required for adulthood. This study explored the perceived impact of residential immersive life skills (RILS) programs on the lives of participants. METHODS: Qualitative interviews were conducted with alumni of three RILS programs. Data were thematically analyzed using a phenomenological approach. RESULTS: Themes identified from fourteen interviews were: (1) enhancing higher-order skills; (2) new notions of independence; and (3) identity change, empowerment, and advocacy. Opportunities to learn and practise a variety of skills in a structured, facilitative environment led to increased competence and motivation to engage in independent activities. Engaging with peers undergoing similar experiences also helped some youth integrate disability into their identity. CONCLUSIONS: Providing youth with physical disabilities opportunities to engage with others sharing similar experiences and challenges is essential. The study contributes toward the development of evidence-based best practices for life skills programs. PMID- 27003565 TI - Inhibition as a Binary Switch for Excitatory Plasticity in Pyramidal Neurons. AB - Synaptic plasticity is thought to induce memory traces in the brain that are the foundation of learning. To ensure the stability of these traces in the presence of further learning, however, a regulation of plasticity appears beneficial. Here, we take up the recent suggestion that dendritic inhibition can switch plasticity of excitatory synapses on and off by gating backpropagating action potentials (bAPs) and calcium spikes, i.e., by gating the coincidence signals required for Hebbian forms of plasticity. We analyze temporal and spatial constraints of such a gating and investigate whether it is possible to suppress bAPs without a simultaneous annihilation of the forward-directed information flow via excitatory postsynaptic potentials (EPSPs). In a computational analysis of conductance-based multi-compartmental models, we demonstrate that a robust control of bAPs and calcium spikes is possible in an all-or-none manner, enabling a binary switch of coincidence signals and plasticity. The position of inhibitory synapses on the dendritic tree determines the spatial extent of the effect and allows a pathway-specific regulation of plasticity. With appropriate timing, EPSPs can still trigger somatic action potentials, although backpropagating signals are abolished. An annihilation of bAPs requires precisely timed inhibition, while the timing constraints are less stringent for distal calcium spikes. We further show that a wide-spread motif of local circuits-feedforward inhibition-is well suited to provide the temporal precision needed for the control of bAPs. Altogether, our model provides experimentally testable predictions and demonstrates that the inhibitory switch of plasticity can be a robust and attractive mechanism, hence assigning an additional function to the inhibitory elements of neuronal microcircuits beyond modulation of excitability. PMID- 27003566 TI - Identification of Genetic Defects Underlying FXII Deficiency in Four Unrelated Chinese Patients. AB - Congenital factor XII (FXII) dexFB01;ciency is a rare autosomal recessive disorder, characterized by a great variability in its clinical manifestations. In this study, we screened for mutations in the F12 gene of 4 unrelated patients with FXII coagulant activity <10% of that of normal human plasma. To investigate the molecular defects in these FXII-deficient patients, we performed FXII mutation screening. By sequencing all coding exons as well as xFB02;anking intronic regions of the F12 gene, 6 different mutations, including 3 missense mutations (Gly341Arg, Glu502Lys and Gly542 Ser), 1 insertion (7142insertC) and 2 deletions (5741-5742 delCA and 6753-6755delACA), were identixFB01;ed on the F12 gene. Three of them (Gly341Arg, 5741-5742delCA and 6753-6755delACA) are reported here for the first time. Computer-based algorithms predicted these missense mutations to be deleterious. This study has increased our knowledge of the mutational spectrum underlying FXII deficiency. PMID- 27003567 TI - [Infra- and supradiaphragmatic urethral injuries. Acute treatment]. AB - BACKGROUND: Urethral injuries are often caused by pelvic fractures or blunt trauma. Drainage of the urinary bladder is the first step of therapy. RESULTS: Urethral injuries are often caused by pelvic fractures or blunt trauma. Drainage of the urinary bladder is the first step of therapy. Standard procedure is the insertion of a suprapubic stent in stable patients without concomitant open injuries in the pelvis area. Endoscopic realignment is useful in patients with pelvic fracture, vaginal, rectal, or bladder injury, who require open surgery. Delayed repair by stricture excision and open urethroplasty with end-to-end anastomosis is the standard procedure. PMID- 27003568 TI - [Urological emergencies]. PMID- 27003569 TI - [Urosepsis. Update on diagnosis and treatment]. AB - BACKGROUND: Sepsis is an acute systemic response to the presence of bacteria and bacterial components in the macroorganism, and urosepsis is defined as sepsis caused by an infection in the urogenital tract. The urogenital tract is considered to be responsible for about 30 % of the cases of septic processes, whereby obstructive uropathy is causative in about 80 % of these cases. Sepsis manifests as an initially predominant proinflammatory response by widespread release of inflammatory mediators as a result of activation of cells responsive to infectious components such as bacterial toxins, which is then accompanied by a counter-regulatory anti-inflammatory response. DIAGNOSIS AND THERAPY: Prior to antibiotic therapy, blood and urine cultures are recommended, while procalcitonin and lactate can be considered diagnostically relevant biomarkers. Furthermore, early imaging to localize the level of obstruction and infectious focus should be carried out. Treatment is divided into causal therapy (antimicrobial therapy and infectious source), supportive therapy (fluids and oxygen administration), and adjunctive therapy (sepsis-specific therapy). PMID- 27003570 TI - [Urinary bladder injuries. Diagnosis and treatment]. AB - BACKGROUND: Injuries of the urinary bladder can be associated with blunt and penetrating abdominal or pelvic trauma. In addition, they can be an iatrogenic complication in open, laparoscopic, and endoscopic urogenital or abdominal surgery. OBJECTIVES: The present article reviews relevant causes of bladder injuries and the subsequent diagnostic and treatment modalities. PMID- 27003571 TI - [Cardiovascular risks of androgen deprivation therapy for prostate cancer]. AB - Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. It has increasingly been used in other stages of the disease as well. Besides well-known side effects caused by the lack of testosterone (impotency, osteoporosis, fatigue, loss of muscle mass), an increase of cardiovascular (CV) morbidity and mortality has recently been discussed in association with ADT. Cardiovascular side effects cannot be sufficiently explained by low testosterone levels. This review gives an overview of the recent literature, interprets the results, and offers clinical consequences. PMID- 27003572 TI - Analysis of tryptase-positive mast cells and immunoexpression of MMP-9 and MMP-13 in periapical lesions. AB - AIM: To evaluate the immunoexpression of tryptase, MMP-9 and MMP-13 in periapical lesions, correlating them with the type of lesion, intensity of the inflammatory infiltrate and thickness of the epithelial lining. METHODOLOGY: Twenty periapical granulomas (PGs), twenty radicular cysts (RCs) and twenty residual radicular cysts (RRCs) were submitted to immunohistochemical analysis using antitryptase, anti-MMP-9 and anti-MMP-13 antibodies. Immunoexpression of MMP-9 and MMP-13 was quantitatively evaluated both in the connective tissue of all lesions and in the epithelial lining of RCs and RRCs. Tryptase-positive mast cells were counted only in the connective tissue. The data were analysed using Kruskal-Wallis and Fisher's exact tests, as well as Spearman's correlation test (P < 0.05). RESULTS: In comparison with RCs and RRCs, PGs exhibited higher immunoexpression of tryptase, MMP-9 and MMP-13 (P = 0.002, P = < 0.001 and P < 0.001, respectively). In comparison with lesions with inflammatory infiltrates grades I and II, lesions with inflammatory infiltrate grade III had higher median percentages of MMP-13 positive cells (P = 0.003) and a tendency for higher expression of MMP-9 (P = 0.059). No significant difference was observed between the expression of the studied markers and epithelial thickness (P > 0.05). There were positive correlations between the number of tryptase-positive mast cells and the immunoexpression of MMP-9, as well as between the immunoexpression of MMP-9 and MMP-13. CONCLUSION: A larger number of tryptase-positive mast cells and greater enzymatic activity of MMP-9 and MMP-13 were found in PGs compared to RCs and RRCs. These findings are a characteristic of the dynamics of periapical diseases. PMID- 27003573 TI - Transfemoral Aortic Valve Implantation with the New Edwards Sapien 3 Valve for Treatment of Severe Aortic Stenosis-Impact of Valve Size in a Single Center Experience. AB - AIMS: The third generation Edwards Sapien 3 (Edwards Lifesciences Inc., Irvine, California) system was optimized to reduce residual aortic regurgitation and vascular complications. METHODS AND RESULTS: 235 patients with severe symptomatic aortic stenosis were prospectively enrolled. Transcatheter aortic valve implantations (TAVI) were performed without general anesthesia by transfemoral approach. Patients were followed for 30 days. Patients received 23mm (N = 77), 26mm (N = 91) or 29mm (N = 67) valve based on pre-procedural 256 multislice computer tomography. Mean oversizing did not differ between the 3 valves. There was no residual moderate or severe aortic regurgitation. Rate of mild aortic regurgitation and regurgitation index did not differ between groups. There was no switch to general anesthesia or conversion to surgery. Rate of major vascular complication was 3.0% with no difference between valve and delivery sheath sizes. Within 30 days rates of all cause mortality (2.6%) and stroke (2.1%) were low. CONCLUSIONS: In patients with severe aortic stenosis transfemoral TAVI with the Edwards Sapien 3 valve without general anesthesia was associated with a high rate of device success, no moderate or severe residual aortic regurgitation, low rates of major vascular complication, mortality and stroke within 30 days with no difference between the 3 valve sizes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02162069. PMID- 27003574 TI - Diffusion-weighted imaging of hepatocellular carcinomas: a retrospective analysis of correlation between apparent diffusion coefficients and histological grade. AB - PURPOSE: To define correlations between the pathological grades of hepatocellular carcinomas (HCCs) and apparent diffusion coefficients (ADCs) derived using breath holding diffusion-weighted imaging (BH-DWI). METHODS: We retrospectively evaluated 94 patients (105 lesions) with pathologically proved HCC who underwent hepatic DWI on a 3.0-T MR platform. HCCs were divided into five groups: well differentiated (n = 10), well-to-moderately differentiated (n = 11), moderately differentiated (n = 51), moderately to poorly differentiated (n = 20), and poorly differentiated (n = 13) groups. The ADCs of carcinomas across different histological grades were compared by one-way analysis of variance. Spearman's rank correlation test was used to analyze correlations between the degree of histopathological differentiation and ADC. Results were corrected for multiple comparisons using the Bonferroni correction. RESULTS: The BH technique yielded ADC values that differed significantly by the extent of differentiation (F = 8.392, p < 0.001). A significant negative correlation was found between the extent of differentiation and ADCs (r = -0.462, p < 0.001). The mean ADC values of poorly differentiated HCCs were significantly lower than the well-, well-to moderately, moderately, and moderately to poorly differentiated HCCs (p values were <0.001, <0.001, 0.003, and 0.031, respectively). CONCLUSION: ADC values obtained with BH-DWI may be of importance to non-invasively predict HCC tumor differentiation, and the extent of histological HCC differentiation was inversely correlated with ADC values. PMID- 27003575 TI - Delayed refractory hyperventilation following endoscopic third ventriculostomy in a 5-year-old boy. AB - We present the case of a 5-year-old boy who developed a delayed onset intractable hyperventilation following endoscopic third ventriculostomy. The proposed aetiology of this exceptionally rare phenomenon is discussed. To our knowledge, previous cases have only been reported in the adult population. PMID- 27003576 TI - Arterial variations around the atlas: a comprehensive review for avoiding neurosurgical complications. AB - INTRODUCTION: Neurosurgical approaches often involve the atlas. Therefore, the arterial relationships and anatomical variations are of paramount importance to the neurosurgeon. METHODS: Using standard search engines, a literature review of arterial variants near the first cervical vertebra was performed. CONCLUSIONS: Arterial variations around the atlas are surgically significant. Awareness of their existence and course may provide better pre-operative planning and surgical intervention, potentially leading to better clinical outcomes. Three-dimensional computed tomography angiography (3D CTA) is an important tool for identifying and diagnosing such abnormalities and should be used when such vascular anomalies are suspected. PMID- 27003578 TI - Antibacterial Effects of a Cell-Penetrating Peptide Isolated from Kefir. AB - Kefir is a traditional fermented milk beverage used throughout the world for centuries. A cell-penetrating peptide, F3, was isolated from kefir by Sephadex G 50 gel filtration, DEAE-52 ion exchange, and reverse-phase high-performance liquid chromatography. F3 was determined to be a low molecular weight peptide containing one leucine and one tyrosine with two phosphate radicals. This peptide displayed antimicrobial activity across a broad spectrum of organisms including several Gram-positive and Gram-negative bacteria as well as fungi, with minimal inhibitory concentration (MIC) values ranging from 125 to 500 MUg/mL. Cellular penetration and accumulation of F3 were determined by confocal laser scanning microscopy. The peptide was able to penetrate the cellular membrane of Escherichia coli and Staphylococcus aureus. Changes in cell morphology were observed by scanning electron microscopy (SEM). The results indicate that peptide F3 may be a good candidate for use as an effective biological preservative in agriculture and the food industry. PMID- 27003577 TI - High level soluble expression and one-step purification of IBDV VP2 protein in Escherichia coli. AB - OBJECTIVES: To improve the expression of soluble IBDV VP2 protein by using different tagged vectors in Escherichia coli. RESULTS: Fusion tags, Grifin, MBP, SUMO, thioredoxin, gamma-crystallin, ArsC and PpiB, enhanced the expression and solubility of VP2 protein. The fusion proteins were purified by Ni-NTA chromatography, MBP-VP2 showed the highest purity about 90 %. After removing the MBP tag, VP2 self-assembled into virus-like particles, ~25 nm diam. Results from AGP suggested the recombinant IBDV VP2 protein identified by reference serum like IBDV. CONCLUSION: All the seven tags enhanced the expression and solubility of IBDV VP2 protein. The recombinant protein self-assembly into virus like particles and possess antigenicity as reference IBDV. PMID- 27003579 TI - Splice form variant and amino acid changes in MDR49 confers DDT resistance in transgenic Drosophila. AB - The ATP-binding cassette (ABC) transporters represent a superfamily of proteins that have important physiological roles in both prokaryotes and eukaryotes. In insects, ABC transporters have previously been implicated in insecticide resistance. The 91-R strain of Drosophila melanogaster has been intensely selected with DDT over six decades. A recent selective sweeps analysis of 91-R implicated the potential role of MDR49, an ABC transporter, in DDT resistance, however, to date the details of how MDR49 may play a role in resistance have not been elucidated. In this study, we investigated the impact of structural changes and an alternative splicing event in MDR49 on DDT-resistance in 91-R, as compared to the DDT susceptible strain 91-C. We observed three amino acid differences in MDR49 when 91-R was compared with 91-C, and only one isoform (MDR49B) was implicated in DDT resistance. A transgenic Drosophila strain containing the 91-R MDR49B isoform had a significantly higher LD50 value as compared to the 91-C MDR49B isoform at the early time points (6 h to 12 h) during DDT exposure. Our data support the hypothesis that the MDR49B isoform, with three amino acid mutations, plays a role in the early aspects of DDT resistance in 91-R. PMID- 27003580 TI - Exercise Training Reverses Structural Microvascular Rarefaction and Improves Endothelium-Dependent Microvascular Reactivity in Rats with Diabetes. AB - BACKGROUND: We evaluated structural microvascular alterations in the skeletal muscle and left ventricle, as well as endothelium-dependent microvascular reactivity in the skeletal muscle, of diabetic rats subjected to long-term aerobic exercise training. METHODS: Diabetes was experimentally induced by a combination of a high-fat diet with a single low dose of streptozotocin (35 mg/kg, i.p.). Animals with diabetes were divided into sedentary (DM+SED) and training groups (DM+TR) and compared with rats without diabetes (CON). We then measured maximal exercise capacity, fasting glucose and insulin, endothelium dependent microvascular reactivity in skeletal muscle, and structural alterations of microvasculature in the skeletal and cardiac muscles. RESULTS: Diabetes induced microvascular rarefaction and reduced endothelium-dependent microvascular reactivity. Physical exercise completely reversed microvascular rarefaction in the skeletal muscle (1.85 +/- 0.05 vs. 1.17 +/- 0.03 capillary/fiber ratio, P < 0.05) and in the left ventricle (0.48 +/- 0.66 vs. 0.25 +/- 0.01 Vv[cap]/Vv[fib] ratio, P < 0.05) compared with the DM+SED group and normalized the microcirculatory responses to acetylcholine in skeletal muscle (CON 38.76 +/- 5.60 vs. DM+TR 30.47% +/- 5.77%). As expected, exercise training increased the maximal velocity and exercise tolerance compared with the DM+SED (P < 0.05) and CON (P < 0.05) groups. Exercise training also reduced fasting glucose (P < 0.05) compared with DM+SED and normalized insulin levels compared with CON. CONCLUSIONS: Our results suggest that long-term physical exercise reverses skeletal and cardiac muscle microvascular rarefaction, as well as impaired endothelium-dependent microvascular reactivity, induced by diabetes in rats. PMID- 27003581 TI - Cognitive Impairment in Patients with Psoriasis: A Cross-Sectional Study Using the Montreal Cognitive Assessment. AB - BACKGROUND: Psoriasis is a multisystem chronic inflammatory disorder that is thought to be associated with cognitive impairment. AIMS: We aimed to investigate cognitive performance using the Montreal Cognitive Assessment (MoCA) in patients with psoriasis. METHODS: In total, 77 patients with psoriasis and 83 age- and sex matched control subjects were enrolled in this prospective cross-sectional study. Physical and/or histopathological findings were used to diagnose psoriasis vulgaris, and patients with psoriasis were evaluated according to disease characteristics, including duration, severity, onset age, medical treatment, and cosmetic involvement. All participants provided sociodemographic data and completed the Beck Depression Inventory. Cognitive functions were evaluated using the MoCA tool. RESULTS: The MoCA scores were significantly lower in the psoriasis group than in the control group (p = 0.004). More psoriasis patients than control subjects presented with deficits in visuospatial domain (p = 0.037) and executive functioning (p = 0.010). In the multivariate model, the presence of psoriasis (odds ratio [OR] 3.64; 95 % confidence interval [CI] 1.65-8.02; p = 0.001), education level (3.74; 95 % CI 1.65-8.48; p = 0.002), and area of residence (3.56; 95 % CI 1.61-7.87; p = 0.002) were found to be independently associated with cognitive impairment in patients with psoriasis and control subjects. On the other hand, no correlations were observed between disease characteristics and cognitive impairment in patients with psoriasis vulgaris (p > 0.05). CONCLUSIONS: The results suggest that psoriasis patients might have early or subtle cognitive impairment, including visuospatial domain and executive functioning. PMID- 27003582 TI - Unusually Slow Electron Cooling to Charge-Transfer State in Gradient CdTeSe Alloy Nanocrystals Mediated through Mn Atom. AB - We have synthesized Mn-doped CdTeSe gradient alloy nanocrystals (NCs) by a colloidal synthetic method, and charge carrier dynamics have been revealed through ultrafast transient absorption (TA) spectroscopy. Due to the reactivity difference between Te and Se, a CdTe-rich core and CdSe-rich shell have been formed in the CdTeSe alloy with the formation of a gradient type II core-shell structure. Electron paramagnetic resonance studies suggest Mn atoms are located in the surface of the alloy NCs. Steady-state optical absorption and emission studies suggest formation of a charge-transfer (CT) state in which electrons are localized in a CdSe-rich shell and holes are localized in a CdTe-rich core which appears in the red region of the spectra. Electron transfer in the CT state is found to take place in the Marcus inverted region. To understand charge-transfer dynamics in the CdTeSe alloy NCs and to determine the effect of Mn doping on the alloy, ultrafast transient absorption studies have been carried out. In the case of the undoped alloy, formation of the CT state is found to take place through electron relaxation to the conduction band of the CT state with a time of 600 fs and through hole relaxation (from the CdSe-rich state to the CdTe-rich state) to the valence band of the CT state with a time scale of 1 ps. However, electron relaxation in the presence of Mn dopants takes place initially via an electron transfer to the Mn 3d state (d(5)) followed by transfer from the Mn 3d state (d(6)) to the CT state, which has been found to take place with a >700 ps time scale in addition to the hole relaxation time of 2 ps. Charge recombination time of the CT state is found to be extremely slow in the Mn-doped CdTeSe alloy NCs as compared to the undoped one, where the Mn atom acts as an electron storage center. PMID- 27003583 TI - Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features. AB - Human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2) has been previously associated with intellectual disability and developmental delay in three patients. Here, we describe six patients with developmental delay, intellectual disability, and dysmorphic features with de novo likely gene damaging variants in HIVEP2 identified by whole-exome sequencing (WES). HIVEP2 encodes a large transcription factor that regulates various neurodevelopmental pathways. Our findings provide further evidence that pathogenic variants in HIVEP2 lead to intellectual disabilities and developmental delay. PMID- 27003584 TI - Decoupling of reaction time-related default mode network activity with cognitive demand. AB - Reaction Time (RT) is associated with increased amplitude of the Blood Oxygen Level Dependent (BOLD) response in task positive regions. Few studies have focused on whether opposing RT-related suppression of task activity also occurs. The current study used two Go/No-go tasks with different cognitive demands to examine regions that showed greater BOLD suppression for longer RT trials. These RT-related suppression effects occurred within the DMN and were task-specific, localizing to separate regions for the two tasks. In the task requiring working memory, RT-related de-coupling of the DMN occurred. This was reflected by opposing RT-BOLD effects for different DMN regions, as well as by reduced positive RT-related Psycho-Physiological Interaction (PPI) connectivity within the DMN and a lack of negative RT-related PPI connectivity between DMN and task positive regions. The results suggest that RT-related DMN suppression is task specific. RT-related de-coupling of the DMN with more complex task demands may contribute to lapses of attention and performance decrements that occur during cognitively-demanding tasks. PMID- 27003585 TI - Amplicon-based semiconductor sequencing of human exomes: performance evaluation and optimization strategies. AB - The Ion Proton platform allows to perform whole exome sequencing (WES) at low cost, providing rapid turnaround time and great flexibility. Products for WES on Ion Proton system include the AmpliSeq Exome kit and the recently introduced HiQ sequencing chemistry. Here, we used gold standard variants from GIAB consortium to assess the performances in variants identification, characterize the erroneous calls and develop a filtering strategy to reduce false positives. The AmpliSeq Exome kit captures a large fraction of bases (>94 %) in human CDS, ClinVar genes and ACMG genes, but with 2,041 (7 %), 449 (13 %) and 11 (19 %) genes not fully represented, respectively. Overall, 515 protein coding genes contain hard-to sequence regions, including 90 genes from ClinVar. Performance in variants detection was maximum at mean coverage >120*, while at 90* and 70* we measured a loss of variants of 3.2 and 4.5 %, respectively. WES using HiQ chemistry showed ~71/97.5 % sensitivity, ~37/2 % FDR and ~0.66/0.98 F1 score for indels and SNPs, respectively. The proposed low, medium or high-stringency filters reduced the amount of false positives by 10.2, 21.2 and 40.4 % for indels and 21.2, 41.9 and 68.2 % for SNP, respectively. Amplicon-based WES on Ion Proton platform using HiQ chemistry emerged as a competitive approach, with improved accuracy in variants identification. False-positive variants remain an issue for the Ion Torrent technology, but our filtering strategy can be applied to reduce erroneous variants. PMID- 27003586 TI - Nanoparticle drug delivery systems and their use in cardiac tissue therapy. AB - Cardiovascular diseases make up one of the main causes of death today, with myocardial infarction and ischemic heart disease contributing a large share of the deaths reported. With mainstream clinical therapy focusing on palliative medicine following myocardial infarction, the structural changes that occur in the diseased heart will eventually lead to end-stage heart failure. Heart transplantation remains the only gold standard of cure but a shortage in donor organs pose a major problem that led to clinicians and researchers looking into alternative strategies for cardiac repair. This review will examine some alternative methods of treatment using chemokines and drugs carried by nanoparticles as drug delivering agents for the purposes of treating myocardial infarction through the promotion of revascularization. We will also provide an overview of existing studies involving such nanoparticulate drug delivery systems, their reported efficacy and the challenges facing their translation into ubiquitous clinical use. PMID- 27003587 TI - MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non metastatic Melanoma B. AB - Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3'-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy. PMID- 27003588 TI - CD64 and Group II Secretory Phospholipase A2 (sPLA2-IIA) as Biomarkers for Distinguishing Adult Sepsis and Bacterial Infections in the Emergency Department. AB - INTRODUCTION: Early diagnosis of sepsis and bacterial infection is imperative as treatment relies on early antibiotic administration. There is a need to develop new biomarkers to detect patients with sepsis and bacterial infection as early as possible, thereby enabling prompt antibiotic treatment and improving the survival rate. METHODS: Fifty-one adult patients with suspected bacterial sepsis on admission to the Emergency Department (ED) of a teaching hospital were included into the study. All relevant cultures and serology tests were performed. Serum levels for Group II Secretory Phospholipase A2 (sPLA2-IIA) and CD64 were subsequently analyzed. RESULTS AND DISCUSSION: Sepsis was confirmed in 42 patients from a total of 51 recruited subjects. Twenty-one patients had culture confirmed bacterial infections. Both biomarkers were shown to be good in distinguishing sepsis from non-sepsis groups. CD64 and sPLA2-IIA also demonstrated a strong correlation with early sepsis diagnosis in adults. The area under the curve (AUC) of both Receiver Operating Characteristic curves showed that sPLA2-IIA was better than CD64 (AUC = 0.93, 95% confidence interval (CI) = 0.83-0.97 and AUC = 0.88, 95% CI = 0.82-0.99, respectively). The optimum cutoff value was 2.13MUg/l for sPLA2-IIA (sensitivity = 91%, specificity = 78%) and 45 antigen bound cell (abc) for CD64 (sensitivity = 81%, specificity = 89%). In diagnosing bacterial infections, sPLA2-IIA showed superiority over CD64 (AUC = 0.97, 95% CI = 0.85-0.96, and AUC = 0.95, 95% CI = 0.93-1.00, respectively). The optimum cutoff value for bacterial infection was 5.63MUg/l for sPLA2-IIA (sensitivity = 94%, specificity = 94%) and 46abc for CD64 (sensitivity = 94%, specificity = 83%). CONCLUSIONS: sPLA2-IIA showed superior performance in sepsis and bacterial infection diagnosis compared to CD64. sPLA2-IIA appears to be an excellent biomarker for sepsis screening and for diagnosing bacterial infections, whereas CD64 could be used for screening bacterial infections. Both biomarkers either alone or in combination with other markers may assist in decision making for early antimicrobial administration. We recommend incorporating sPLA2-IIA and CD64 into the diagnostic algorithm of sepsis in ED. PMID- 27003589 TI - Effectiveness of Multiple-Strategy Community Intervention in Reducing Geographical, Socioeconomic and Gender Based Inequalities in Maternal and Child Health Outcomes in Haryana, India. AB - OBJECTIVE: The implemented multiple-strategy community intervention National Rural Health Mission (NRHM) between 2005 and 2012 aimed to reduce maternal and child health (MCH) inequalities across geographical, socioeconomic and gender categories in India. The objective of this study is to quantify the extent of reduction in these inequalities pre- and post-NRHM in Haryana, North India. METHODS: Data of district-level household surveys (DLHS) held before (2002-04), during (2007-08), and after (2012-13) the implementation of NRHM has been used. Geographical, socioeconomic and gender inequalities in maternal and child health were assessed by estimating the absolute differences in MCH indicators between urban and rural areas, between the most advantaged and least advantaged socioeconomic groups and between male and female children. Logistic regression analyses were done to observe significant differences in these inequalities between 2005 and 2012. RESULTS: There were significant improvements in all MCH indicators (p<0.05). The geographical and socioeconomic differences between urban and rural areas, and between rich and poor were significantly (p<0.05) reduced for pregnant women who had an institutional delivery (geographical difference declining from 22% to 7.6%; socioeconomic from 48.2% to 13%), post-natal care within 2 weeks of delivery (2.8% to 1.5%; 30.3% to 7%); and for children with full vaccination (10% to 3.5%, 48.3% to 14%) and who received oral rehydration solution (ORS) for diarrhea (11% to -2.2%; 41% to 5%). Inequalities between male and female children were significantly (p<0.05) reversed for full immunization (5.7% to -0.6%) and BCG immunization (1.9 to -0.9 points), and a significant (p<0.05) decrease was observed for oral polio vaccine (4.0% to 0%) and measles vaccine (4.2% to 0.1%). CONCLUSIONS: The implemented multiple-strategy community intervention National Rural Health Mission (NRHM) between 2005 and 2012 might have resulted in significant reductions in geographical, socioeconomic and gender inequalities in MCH in Haryana, as causal relationships cannot be established with descriptive research. PMID- 27003590 TI - Examining the relationship between hormone therapy and dry-eye syndrome in postmenopausal women: a cross-sectional comparison study. AB - OBJECTIVE: To examine the relationship between hormone therapy (HT) and dry-eye syndrome (DES) in postmenopausal women. METHODS: A cross-sectional study was performed on 360 postmenopausal women. They were grouped into two groups. Group 1 was the control group (n = 189) without DES symptoms and which did not receive HT. Group 2 (n = 177) consisted of women with DES symptoms. Group 2 was randomly grouped into two further categories-group 2A (n = 90) that received estrogen-only HT, and group 2B (n = 87) in which participants were treated with a combination of estrogen and progesterone HT. The severity of symptom levels was determined using the Ocular Surface Disease Index levels that identify the extent of the relationship between the sex hormones and DES. A further comparison of the severity of symptoms among women using HT and those not using HT was used to establish the relationship between HT and DES in postmenopausal women. RESULTS: There was a significant variation in the severity levels of DES across women not using HT and those who were using HT (group 2A and 2B) (F[2, 357] = 974.186, P < 0.0001). Also, there was a significant variation in the severity levels of DES based on dosage levels (<1 and >1 mg/d) across women using HT (group 2A and 2B) (F[2, 357] = 302.513, P < 0.0001). Finally, there was a significant variation in the severity levels of DES based on duration levels 12, 36, and 48 months across women using HT (group 2A and 2B) (F[3, 356] = 218.266, P < 0.0001). CONCLUSIONS: The current study findings have negated the previous assumption that HT use contributes to a reduction in DES among postmenopausal women. Instead, prolonged HT use seems to increase the risk of DES. PMID- 27003591 TI - The role of pharmacotherapy in the prevention of sudden cardiac death in patients with heart failure. AB - Sudden cardiac death remains a significant threat to the survival of patients with heart failure. Long-term cardiac remodeling predisposes these patients to develop malignant ventricular arrhythmias. Permanent implantable and temporary external defibrillators remain a mainstay for the prevention of sudden cardiac death in this population. For decades, researchers have attempted to identify reliable drug therapies to avoid such arrhythmias; however, to date, success has been inconsistent. This review aims to explore the evidence defining the role of drug therapies for direct and indirect suppression of arrhythmias that may cause sudden cardiac death in patients with heart failure. PMID- 27003592 TI - Stem cell progeny contribute to the schistosome host-parasite interface. AB - Schistosomes infect more than 200 million of the world's poorest people. These parasites live in the vasculature, producing eggs that spur a variety of chronic, potentially life-threatening, pathologies exacerbated by the long lifespan of schistosomes, that can thrive in the host for decades. How schistosomes maintain their longevity in this immunologically hostile environment is unknown. Here, we demonstrate that somatic stem cells in Schistosoma mansoni are biased towards generating a population of cells expressing factors associated exclusively with the schistosome host-parasite interface, a structure called the tegument. We show cells expressing these tegumental factors are short-lived and rapidly turned over. We suggest that stem cell-driven renewal of this tegumental lineage represents an important strategy for parasite survival in the context of the host vasculature. PMID- 27003593 TI - Brain-wide mapping of neural activity controlling zebrafish exploratory locomotion. AB - In the absence of salient sensory cues to guide behavior, animals must still execute sequences of motor actions in order to forage and explore. How such successive motor actions are coordinated to form global locomotion trajectories is unknown. We mapped the structure of larval zebrafish swim trajectories in homogeneous environments and found that trajectories were characterized by alternating sequences of repeated turns to the left and to the right. Using whole brain light-sheet imaging, we identified activity relating to the behavior in specific neural populations that we termed the anterior rhombencephalic turning region (ARTR). ARTR perturbations biased swim direction and reduced the dependence of turn direction on turn history, indicating that the ARTR is part of a network generating the temporal correlations in turn direction. We also find suggestive evidence for ARTR mutual inhibition and ARTR projections to premotor neurons. Finally, simulations suggest the observed turn sequences may underlie efficient exploration of local environments. PMID- 27003594 TI - Huntingtin's spherical solenoid structure enables polyglutamine tract-dependent modulation of its structure and function. AB - The polyglutamine expansion in huntingtin protein causes Huntington's disease. Here, we investigated structural and biochemical properties of huntingtin and the effect of the polyglutamine expansion using various biophysical experiments including circular dichroism, single-particle electron microscopy and cross linking mass spectrometry. Huntingtin is likely composed of five distinct domains and adopts a spherical alpha-helical solenoid where the amino-terminal and carboxyl-terminal regions fold to contain a circumscribed central cavity. Interestingly, we showed that the polyglutamine expansion increases alpha-helical properties of huntingtin and affects the intramolecular interactions among the domains. Our work delineates the structural characteristics of full-length huntingtin, which are affected by the polyglutamine expansion, and provides an elegant solution to the apparent conundrum of how the extreme amino-terminal polyglutamine tract confers a novel property on huntingtin, causing the disease. PMID- 27003595 TI - Can pelvic floor muscle training improve quality of life in men with mild to moderate post-stroke and lower urinary tract symptoms? AB - BACKGROUND: Lower urinary tract symptoms (LUTS) have a significant impact on quality of life (QoL) in post-stroke patients. AIM: The aim of this study was to evaluate the effect of pelvic floor muscle training (PFMT) on QoL parameters in men with post-stroke LUTS. DESIGN: Randomized, controlled and single-blinded trial. SETTING: Outpatients, University Hospital. POPULATION: Thirty-one men, median age 68 (interquartile range 60-74) years, with post-stroke LUTS were included. Thirty participants completed the study. METHODS: The participants randomized to the treatment group were treated in a systematic, controlled and intensive PFMT program over 3 months (12 weekly sessions). The participants randomized to the control group did not receive specific LUTS treatment. The effect was measured on the 36-Item Short Form Health Survey (SF-36) and the Nocturia Quality-of-Life (N-QoL) Questionnaire. RESULTS: The results on SF-36 indicated significant improvement within pre- and post-test in the domains emotional role (median 77 to 100, P=0.03) and vitality (median 65 to 70, P=0.03) in the treatment group, but not the control group. There were no statistically significant differences between groups at pre-test, post-test or 6-month follow up. The results on N-QoL indicated statistically significant differences between pre- and post-test in the bother/concern domain in both groups and in sleep/energy for the control group, but not the treatment group. There were no statistically significant differences between groups. CONCLUSIONS: PFMT may improve the emotional health and vitality domains of QoL in men with mild to moderate post-stroke and LUTS; however the improvements in the treatment group were not significantly better than for the control group. PFMT did not improve nocturia-related QoL. CLINICAL REHABILITATION IMPACT: This study is the first to evaluate the effect of PFMT on QoL parameters in men with mild to moderate post stroke and LUTS. The results indicate some short-term effect on SF-36 but none on N-QoL. However, further studies with larger sample sizes and with less restrictive inclusion and exclusion criteria are requested. PMID- 27003596 TI - Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis. AB - The space-time pattern and environmental drivers (land cover, climate) of bovine anaplasmosis in the Midwestern state of Kansas was retrospectively evaluated using Bayesian hierarchical spatio-temporal models and publicly available, remotely-sensed environmental covariate information. Cases of bovine anaplasmosis positively diagnosed at Kansas State Veterinary Diagnostic Laboratory (n = 478) between years 2005-2013 were used to construct the models, which included random effects for space, time and space-time interaction effects with defined priors, and fixed-effect covariates selected a priori using an univariate screening procedure. The Bayesian posterior median and 95% credible intervals for the space time interaction term in the best-fitting covariate model indicated a steady progression of bovine anaplasmosis over time and geographic area in the state. Posterior median estimates and 95% credible intervals derived for covariates in the final covariate model indicated land surface temperature (minimum), relative humidity and diurnal temperature range to be important risk factors for bovine anaplasmosis in the study. The model performance measured using the Area Under the Curve (AUC) value indicated a good performance for the covariate model (> 0.7). The relevance of climatological factors for bovine anaplasmosis is discussed. PMID- 27003597 TI - Circulating miRNAs as novel potential biomarkers for esophageal squamous cell carcinoma diagnosis: a meta-analysis update. AB - Early detection of esophageal squamous cell carcinoma (ESCC) is urgently needed to reduce the high morbidity and mortality of disease. Circulating microRNAs (miRNAs) are promising molecular biomarkers for ESCC prediction. We performed a comprehensive meta-analysis to systematically evaluate the diagnostic accuracy of circulating miRNAs in diagnosis of ESCC patients. Eligible studies were identified and assessed for quality employing multiple search strategies. Summary estimates for sensitivity, specificity, and other measures of accuracy of miRNAs in the diagnosis of ESCC were pooled using the bivariate random effects model. A total of 27 studies from 11 published articles were included in the meta analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating miRNAs for the diagnosis of ESCC were 79.9% (95% confidence intervals [CI]: 76.2%-83.1%), 81.3% (95% CI: 75.7-85.9), 4.27 (95%CI: 3.27-5.58), 0.25 (95% CI: 0.21-0.29), and 17.29 (95% CI: 12.01-24.86), respectively. The area under the summary receiver operating characteristic curve was 0.87 (95% CI: 0.84-0.90). The subgroup analyses based on research country (China vs. Japan), specimen type (plasma vs. serum), miRNAs profiling (single vs. multiple), and test method (screening vs. candidate; Taqman vs. SYBR) indicated no significant difference in the diagnostic accuracy of each subgroup. Collectively, our findings indicate that circulating miRNAs have significant potential to be used as noninvasive biomarkers for early detection of ESCC. Moreover, the subgroup analyses demonstrated the feasibility of using blood miRNAs as an ESCC diagnostic biomarker in Japanese and Chinese populations. Further, both plasma and serum are recommended as clinical specimens for miRNA detection. Further studies will be needed to validate these findings using larger numbers of patients. PMID- 27003598 TI - A review on pregnancy after intestinal transplantation. AB - The largest experience of pregnancy after solid organ transplantation is recorded in renal and liver recipients. Intestinal/multivisceral transplantation has shown steady improvements in graft and patient survival over the past 20 years and is rapidly becoming more established: the first pregnancy after this procedure was described 10 years ago, and so far eight cases of pregnancies with 100% successful live births have been reported worldwide. Specifically to this procedure, there are 2 factors to be considered in case of pregnancy: absorptive function of transplanted bowel and higher need of immune-suppressants. Close monitoring of renal function and of the graft by endoscopies and biopsies can be considered during the pregnancy to prevent episodes of rejection or enteritis, preserving the fetus by temporary malnutrition. As more intestinal transplant patients are surviving and regaining reproductive function, it is important to report this option to female recipients and to their health-care professionals. PMID- 27003599 TI - Comprehensive Definition of the SigH Regulon of Mycobacterium tuberculosis Reveals Transcriptional Control of Diverse Stress Responses. AB - Expression of SigH, one of 12 Mycobacterium tuberculosis alternative sigma factors, is induced by heat, oxidative and nitric oxide stresses. SigH activation has been shown to increase expression of several genes, including genes involved in maintaining redox equilibrium and in protein degradation. However, few of these are known to be directly regulated by SigH. The goal of this project is to comprehensively define the Mycobacterium tuberculosis genes and operons that are directly controlled by SigH in order to gain insight into the role of SigH in regulating M. tuberculosis physiology. We used ChIP-Seq to identify in vivo SigH binding sites throughout the M. tuberculosis genome, followed by quantification of SigH-dependent expression of genes linked to these sites and identification of SigH-regulated promoters. We identified 69 SigH binding sites, which are located both in intergenic regions and within annotated coding sequences in the annotated M. tuberculosis genome. 41 binding sites were linked to genes that showed greater expression following heat stress in a SigH-dependent manner. We identified several genes not previously known to be regulated by SigH, including genes involved in DNA repair, cysteine biosynthesis, translation, and genes of unknown function. Experimental and computational analysis of SigH-regulated promoter sequences within these binding sites identified strong consensus -35 and -10 promoter sequences, but with tolerance for non-consensus bases at specific positions. This comprehensive identification and validation of SigH-regulated genes demonstrates an extended SigH regulon that controls an unexpectedly broad range of stress response functions. PMID- 27003601 TI - Biopsy and Noninvasive Methods to Assess Progression of Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of histopathologic features, ranging from isolated hepatic steatosis, to steatohepatitis with evidence of hepatocellular injury and fibrosis, to cirrhosis. The diagnosis and determination of NAFLD prognosis requires clinical and histopathologic assessments. Liver biopsy still is regarded as the reference for differentiating steatosis (NAFL) from nonalcoholic steatohepatitis, for staging hepatic fibrosis, and for identifying NAFLD in patients with other chronic liver disease. Standardized grading and staging histologic scoring systems, such as the NAFLD activity score and the steatosis, activity, and fibrosis score, can help guide clinical decisions and assess outcomes of clinical trials. Improved understanding of the pathophysiology of NAFLD and technologic advances have led to algorithms that can be used to assess serum biomarkers and imaging methods that are noninvasive alternatives to biopsy collection and analysis. We review the advantages and limitations of biopsy analysis and noninvasive tests as diagnostic and prognostic tools for patients with NAFLD. We also discuss techniques to improve dynamic histopathology assessment, and emerging blood and imaging biomarkers of fibrogenesis. PMID- 27003600 TI - Comparison of the Phenotype and Approach to Pediatric vs Adult Patients With Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is one of the main chronic noncommunicable diseases in Westernized societies; its worldwide prevalence has doubled during the last 20 years. NAFLD has serious health implications not only for adults, but also for children. However, pediatric NAFLD is not only an important global problem in itself, but it is likely to be associated with increases in comorbidities, such as metabolic syndrome and cardiovascular diseases. There are several differences between NAFLD in children and adults, and it is not clear whether the disease observed in children is the initial phase of a process that progresses with age. The increasing prevalence of pediatric NAFLD has serious implications for the future adult population requiring appropriate action. Studies of NAFLD progression, pathogenesis, and management should evaluate disease phenotypes in children and follow these over the patient's lifetime. We review the similarities and differences of NAFLD between children and adults. PMID- 27003602 TI - Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity. AB - BACKGROUND & AIMS: Childhood obesity is increasing and is associated with adult obesity. Antibiotics have been used to promote weight gain in livestock for several decades. Antibiotics are commonly prescribed for children, but it is not clear how exposure to antibiotics early in life affects risk for obesity. We performed a population-based cohort study to assess the association between antibiotic exposure before age 2 years and obesity at age 4 years. METHODS: We performed a retrospective cohort study of 21,714 children in The Health Improvement Network-a population-representative dataset of >10 million individuals derived from electronic medical records from 1995 through 2013 in the United Kingdom. Eligible subjects were registered within 3 months of birth with complete follow-up and height and weight were recorded within 12 months of their 4th birthday. Antibiotic exposure was assessed before age 2 years, and classified based on anti-anaerobic activity. The primary outcome was obesity at age 4 years. We performed logistic regression analyses, adjusting for maternal and sibling obesity, maternal diabetes, mode of delivery, socioeconomic status, year and country of birth, and urban dwelling. RESULTS: In the cohort, 1306 of the children (6.4%) were obese at 4 years of age. Antibiotic exposure was associated with an increased risk of obesity at 4 years (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.07-1.38). ORs increased with repeated exposures: for 1-2 prescriptions, OR = 1.07 (95% CI, 0.91-1.23); for 3-5 prescriptions, OR = 1.41 (95% CI, 1.20-1.65); and for 6 or more prescriptions, OR = 1.47 (95% CI, 1.19-1.82). Antifungal agents were not associated with obesity (OR = 0.81; 95% CI, 0.59-1.11). CONCLUSIONS: Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity. PMID- 27003603 TI - Loss of P53 Function Activates JAK2-STAT3 Signaling to Promote Pancreatic Tumor Growth, Stroma Modification, and Gemcitabine Resistance in Mice and Is Associated With Patient Survival. AB - BACKGROUND & AIMS: One treatment strategy for pancreatic ductal adenocarcinoma is to modify, rather than deplete, the tumor stroma. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) is associated with progression of pancreatic and other solid tumors. We investigated whether loss of P53 function contributes to persistent activation of STAT3 and modification of the pancreatic tumor stroma in patients and mice. METHODS: Stat3, Il6st (encodes gp130), or Trp53 were disrupted, or a mutant form of P53 (P53R172H) or transgenic sgp130 were expressed, in mice that developed pancreatic tumors resulting from expression of activated KRAS (KrasG12D, KC mice). Pancreata were collected and analyzed by immunohistochemistry, in situ hybridization, quantitative reverse transcription polymerase chain reaction (qPCR), or immunoblot assays; fluorescence-activated cell sorting was performed to identify immune cells. We obtained frozen pancreatic tumor specimens from patients and measured levels of phosphorylated STAT3 and P53 by immunohistochemistry; protein levels were associated with survival using Kaplan-Meier analyses. We measured levels of STAT3, P53, ligands for gp130, interleukin 6, cytokines, sonic hedgehog signaling, STAT3 phosphorylation (activation), and accumulation of reactive oxygen species in primary pancreatic cells from mice. Mice with pancreatic tumors were given gemcitabine and a Janus kinase 2 (JAK2) inhibitor; tumor growth was monitored by 3-dimensional ultrasound. RESULTS: STAT3 was phosphorylated constitutively in pancreatic tumor cells from KC mice with loss or mutation of P53. Tumor cells of these mice accumulated reactive oxygen species and had lower activity of the phosphatase SHP2 and prolonged phosphorylation of JAK2 compared with tumors from KC mice with functional P53. These processes did not require the gp130 receptor. Genetic disruption of Stat3 in mice, or pharmacologic inhibitors of JAK2 or STAT3 activation, reduced fibrosis and the numbers of pancreatic stellate cells in the tumor stroma and altered the types of immune cells that infiltrated tumors. Mice given a combination of gemcitabine and a JAK2 inhibitor formed smaller tumors and survived longer than mice given control agents; the tumor stroma had fewer activated pancreatic stellate cells, lower levels of periostin, and alterations in collagen production and organization. Phosphorylation of STAT3 correlated with P53 mutation and features of infiltrating immune cells in human pancreatic tumors. Patients whose tumors had lower levels of phosphorylated STAT3 and functional P53 had significantly longer survival times than patients with high levels of phosphorylated STAT3 and P53 mutation. CONCLUSIONS: In pancreatic tumors of mice, loss of P53 function activates JAK2-STAT3 signaling, which promotes modification of the tumor stroma and tumor growth and resistance to gemcitabine. In human pancreatic tumors, STAT3 phosphorylation correlated with P53 mutation and patient survival time. Inhibitors of this pathway slow tumor growth and stroma formation, alter immune cell infiltration, and prolong survival of mice. Transcript profiling: ArrayExpress accession number: E-MTAB-3278. PMID- 27003605 TI - Wnt/beta-catenin signaling mediates the seizure-facilitating effect of postischemic reactive astrocytes after pentylenetetrazole-kindling. AB - Ischemia not only leads to tissue damage, but also induces seizures, which in turn worsens the outcome of ischemia. Recent studies have revealed the impaired homeostatic functions of reactive astrocytes, which were thought to facilitate the development of seizures. However, how this phenotype of reactive astrocytes is regulated remains unclear. Here, using pentylenetetrazole (PTZ)-kindling model, we investigated the roles of reactive astrocytes and their intracellular Wnt/beta-catenin signaling in the ischemia-increased seizure susceptibility. Our data showed that somatosensory cortical ischemia significantly increased the susceptibility to PTZ-induced seizure. Genetic ablation of Nestin-positive reactive astrocytes significantly decreased the incidence and severity of seizures. By using a Wnt signaling reporter mice line Topgal mice, we found that Wnt/beta-catenin signaling was upregulated in reactive astrocytes after ischemia. Depletion of beta-catenin in reactive astrocytes significantly decreased the susceptibility of seizures and the expression of c-Fos induced by PTZ in the ischemic cortex. Overexpression of beta-catenin in reactive astrocytes, in contrast, significantly increased seizure susceptibility and the expression of c Fos. Furthermore, the expression of aquaporin-4 (AQP-4) and inwardly rectifying K(+) channel 4.1 (Kir4.1), two molecules reportedly associated with seizure development, was oppositely affected in reactive astrocytes with beta-catenin depletion or overexpression. Taken together, these data indicated that astrocytic Wnt/beta-catenin signaling accounts, at least partially, for the ischemia increased seizure susceptibility. Inhibiting Wnt/beta-catenin signaling may be utilized in the future for preventing postischemic seizures. PMID- 27003604 TI - Polyclonal Crypt Genesis and Development of Familial Small Intestinal Neuroendocrine Tumors. AB - BACKGROUND & AIMS: Small intestinal neuroendocrine tumors (SI-NETs) are serotonin secreting well-differentiated neuroendocrine tumors believed to originate from enterochromaffin (EC) cells. Intestinal stem cell (ISC) are believed to contribute to the formation of SI-NETs, although little is known about tumor formation or development. We investigated the relationship between EC cells, ISCs, and SI-NETs. METHODS: We analyzed jejuno-ileal tissue specimens from 14 patients with familial SI-NETs enrolled in the Natural History of Familial Carcinoid Tumor study at the National Institutes of Health from January 2009 to December 2014. Frozen and paraffin-embedded tumor tissues of different stages and isolated crypts were analyzed by in situ hybridization and immunohistochemistry. Tumor clonality was assessed by analyses of mitochondrial DNA. RESULTS: We identified multifocal aberrant crypt-containing endocrine cell clusters (ACECs) that contain crypt EC cell microtumors in patients with familial SI-NETs. RNA in situ hybridization revealed expression of the EC cell and reserve stem cell genes TPH1, BMI1, HOPX, and LGR5(low), in the ACECs and more advanced extraepithelial tumor nests. This expression pattern resembled that of reserve EC cells that express reserve ISC genes; most reside at the +4 position in normal crypts. The presence of multifocal ACECs from separate tumors and in the macroscopic tumor free mucosa indicated widespread, independent, multifocal tumorigenesis. Analyses of mitochondrial DNA confirmed the independent origin of the ACECs. CONCLUSIONS: Familial SI-NETs originate from a subset of EC cells (reserve EC cells that express reserve ISC genes) via multifocal and polyclonal processes. Increasing our understanding of the role of these reserve EC cells in the genesis of multifocal SI-NETs could improve diagnostic and therapeutic strategies for this otherwise intractable disease. PMID- 27003606 TI - A gel aspiration-ejection system for the controlled production and delivery of injectable dense collagen scaffolds. AB - A gel aspiration-ejection (GAE) system has been developed for the advanced production and delivery of injectable dense collagen (I-DC) gels of unique collagen fibrillar densities (CFDs). Through the creation of negative pressure, GAE aspirates prefabricated highly hydrated collagen gels into a needle, simultaneously inducing compaction and meso-scale anisotropy (i.e., fibrillar alignment) on the gels, and by subsequent reversal of the pressure, I-DC gels can be controllably ejected. The system generates I-DC gels with CFDs ranging from 5 to 32 wt%, controlling the initial scaffold microstructure, anisotropy, hydraulic permeability, and mechanical properties. These features could potentially enable the minimally invasive delivery of more stable hydrogels. The viability, metabolic activity, and differentiation of seeded mesenchymal stem cells (MSCs) was investigated in the I-DC gels of distinct CFDs and extents of anisotropy produced through two different gauge needles. MSC osteoblastic differentiation was found to be relatively accelerated in I-DC gels that combined physiologically relevant CFDs and increased fibrillar alignment. The ability to not only support homogenous cell seeding, but also to direct and accelerate their differentiation through tissue-equivalent anisotropy, creates numerous opportunities in regenerative medicine. PMID- 27003607 TI - Wavelength-resolved simultaneous photoelectrochemical bifunctional sensor on single interface: A newly in vitro approach for multiplexed DNA monitoring in cancer cells. AB - Currently, the photoelectrochemical (PEC) strategies can just achieve single analyte detection on a single interface with limited detection efficiency. It is highly valuable but full of challenge to develop a PEC biosensor for multiple analytes evaluation on a single interface. For this point, the wavelength selective photoactive materials, which could generate separated photocurrents under excitation lights with certain wavelengths, were mainly important to overcome this challenge. Herein, these wavelength-selective photoactive materials were successfully synthesized and served as signal indicators to construct a novel PEC biosensor for multiple analytes evaluation on a single interface for the first time. Moreover, an enzyme-assisted target recycling amplification strategy was introduced for ultrasensitive monitoring. As a result, the proposed PEC biosensor showed excellent analytical performance for both oral cancer (ORVOA 1) gene and p53 gene down to attomolar level. In addition, the fabricated PEC biosensor was employed to evaluate ORVOA 1 gene and p53 gene in Hela cells. This assay has laid the foundation for fabrication of simple, ultrasensitive and economical PEC diagnostic devices to detect multiple analytes in cells, which paved a new avenue for early diagnosis of cancer with higher efficiency and accuracy. PMID- 27003608 TI - Array-based identification of triple-negative breast cancer cells using fluorescent nanodot-graphene oxide complexes. AB - Early and accurate diagnosis of breast cancer holds great promise to improve treatability and curability. Here, we report the usage of six luminescent nanodot graphene oxide complexes as novel fluorescent nanoprobes in a sensing array capable of effectively identifying healthy, cancerous, and metastatic human breast cells. The sensory system is based on the utilization of nanoprobe graphene oxide sensor elements that can be disrupted in the presence of breast cells to give fluorescent readouts. Using this multichannel sensor, we have successfully identified breast cancer cells and distinguished between estrogen receptor positive, human epidermal growth factor receptor-2 positive, and triple negative phenotypes. This approach also allows cell identification at high sensitivity (200 cells) with high reproducibility. The unknown cell sample analysis indicates that the sensor is able to identify 49 out of 50 breast cell samples correctly, with a detection accuracy of 98%. Taken together, this array based luminescent nanoprobe-graphene oxide sensing platform presents a useful cell screening tool with potential applications in biomedical diagnostics. PMID- 27003610 TI - Structure-Performance Investigation of Thioxanthone Derivatives for Developing Color Tunable Highly Efficient Thermally Activated Delayed Fluorescence Emitters. AB - Thioxanthone derivatives consisting of undecorated carbazole as an electron donor and thioxanthone (TXO) or 9H-thioxanthen-9-one-S,S-dioxide (SOXO) as an electron acceptor in a donor-acceptor (D-A) or donor-acceptor-donor (D-A-D) structure were developed as thermally activated delayed fluorescence emitters to fabricate highly efficient fluorescent organic light emitting diodes. Their emission color was successfully tuned from blue to yellow by changing the sulfur atom valence state of the thioxanthone unit to tune intramolecular charge transfer effect. Their thermal, electrochemical, photophysical, and electroluminescent properties, and theoretical calculations were systematically investigated to illustrate the molecular structure and property relationships. Maximum external quantum efficiency (EQE) of 13.6% with Commission Internationale de L'Eclairage coordinates of (0.37, 0.57) was achieved for green light emission CzSOXO consisting of SOXO and carbazole in a D-A structure. Blue light emission CzTXO and DCzTXO consisting of TXO and carbazole in a D-A and D-A-D structure could also give EQE values exceeding 11%. Their efficiency roll-off with increasing current density was simulated by adopting triplet-triplet annihilation model, indicating that the TXO derivatives suffer more severe efficiency roll-off because of their relatively long delayed fluorescence lifetime (tau(D)). PMID- 27003611 TI - Phosphoproteome analysis of B. cinerea in response to different plant-based elicitors. AB - The phytopathogen Botrytis cinerea is a ubiquitous fungus with a high capacity to adapt its metabolism to different hosts and environmental conditions in order to deploy a variety of virulence and pathogenicity factors and develop a successful plant infection. Here we report the first comparative phosphoproteomic study of B. cinerea, aimed to analyze the phosphoprotein composition of the fungus and its changes under different phenotypical conditions induced by two different carbon sources as plant based elicitors: glucose and deproteinized tomato cell wall (TCW). A total of 2854 and 2269 different phosphosites (2883 and 1137 phosphopeptides) were identified in glucose and TCW respectively, which map to 1338 phosphoproteins in glucose and 733 in TCW. Out of the identified phosphoproteins, 173 were exclusively found when glucose was the only carbon source and 11 when the carbon source was TCW. Differences in the pattern of phosphorylation-sites were also detected according to the carbon source. Gene ontology classification of the identified phosphoproteins showed that most of the characteristic proteins of the different carbon sources were related to signalling and transmembrane transport, thus highlighting the importance of these processes in the fungal adaptation to the surrounding conditions. BIOLOGICAL SIGNIFICANCE: The characterization of the B. cinerea phosphoproteome under different induction conditions reported here is the first comparative phosphoproteomic approach in this model phytopathogenic fungus. The identified phosphopeptides contribute to expand the map of known phosphoproteins in this pathogen and the observed changes according to the used carbon source contribute to understand the adaptation of the fungus to the environment changes. This knowledge improves the understanding of the adaptation mechanism, defines the role of the phosphoproteins involved in this process, and enables the advance in the design of novel strategies against the fungi. PMID- 27003612 TI - Proteomic analysis of preovulatory follicular fluid reveals differentially abundant proteins in less fertile dairy cows. AB - The follicular fluid (FF) proteome can provide an indication of follicular quality. High-yielding dairy cows suffer from low fertility, which could be related to follicular function. However, the proteome of preovulatory follicles has never been described in cows. Our objectives were to: 1) define the bovine preovulatory FF proteome, and 2) examine differentially abundant proteins in FF of controls (CTL, n=10) and less fertile cows (LFC; failed to conceive following >=6 inseminations, n=8). Follicles >=7mm in diameter were aspirated in vivo, and estradiol (E2) and progesterone (P4) were examined. The FF from 10 preovulatory follicles (E2/P4>1) was analyzed; E2 was higher and follicle diameter tended to be larger in LFC. As aspirations were conducted at a fixed time, this suggests accelerated follicular growth in LFC. The 219 identified and quantified proteins consisted mainly of binding proteins, proteases, receptor ligands, enzymes and transporters. Differential abundance of 8 relevant proteins was found in LFC compared to CTL: SERPINA1, TIMP2, ITIH1, HSPG2, C8A, COL1A2, F2, and IL1RAP. These proteins could influence follicular function-e.g., decreased SERPINA1 may be related to accelerated follicular growth-and therefore, further examination of their roles in the etiology of LFC is warranted. SIGNIFICANCE: High yielding dairy cows suffer from infertility that leads to major economic losses worldwide. In Israel, about 30% of dairy cows fail to conceive following >=4 inseminations. The etiology of this low fertility is multifactorial and remains a serious challenge. Follicular fluid proteome can provide indication to follicular quality, yet the proteome of pre-ovulatory follicles has not been described in cows. This work examined the differential abundance of proteins in less fertile dairy cows compared to controls, and found 8 relevant novel proteins that could influence follicular function. The role of these proteins in the etiology of less fertile cows should be further examined. PMID- 27003613 TI - Tackling probiotic and gut microbiota functionality through proteomics. AB - Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Many strains exert their beneficial effects after transiently colonizing the human gut, where they interact with the rest of the intestinal microorganisms and with the host mucosa. Indeed the human gut harbours a huge number of microorganisms also known as gut microbiota. Imbalances in the relative abundances of the individual components of the gut microbiota may determine the health status of the host and alterations in specific groups have been related to different diseases and metabolic disorders. Proteomics provide a set of high-throughput methodologies for protein identification that are extremely useful for studying probiotic functionality and helping in the assessment of specific health-promoting activities, such as their immunomodulatory activity, the intestinal colonization processes, and the crosstalk mechanisms with the host. Furthermore, proteomics have been used to identify markers of technological performance and stress adaptation, which helps to predict traits such as behaviour into food matrices and ability to survive passage through the gastrointestinal tract. The aim of this review is to compile studies in which proteomics have been used to assess probiotic functionality and to identify molecular players supporting their mechanisms of action. SIGNIFICANCE: Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Molecular basis underlying the functional properties of probiotic bacteria responsible for the health promoting effects have been in the background for many years. Breakthrough of omics technologies in the probiotic and microbiota fields has had a very relevant impact in the elucidation of probiotic mechanisms and in the procedures to select these microorganisms, based on solid scientific evidence. It is unquestionable that, in the near future, the evolution of proteomic techniques will play a pivotal role in the generation of knowledge about the functions of probiotics and gut commensals, still a pending issue in the field of intestinal microbiomics. PMID- 27003614 TI - microRNA-7 Protects Against 1-Methyl-4-Phenylpyridinium Iodide-Induced Cell Apoptosis in SH-SY5Y Cells by Directly Targeting Krupple-Like Factor 4. AB - This study intended to investigate the role and underling mechanism of microRNA-7 (miR-7) on neuronal death in Parkinson's disease (PD). Human neuroblastoma cell line SH-SY5Y was employed and 1-methyl-4-phenylpyridinium iodide [MPP(+)] was used to generate PD model in vitro. Furthermore, an upregulation of miR-7 was performed in SH-SY5Y by transfection with miR-7 mimics. Cell viability and cell apoptosis were determined. Moreover, the target and the mechanism of miR-7 in MPP(+)-induced cell death were also investigated. The upregulation of miR-7 promoted cell viability and suppressed cell apoptosis in MPP(+)-treated SH-SY5Y cells. Furthermore, miR-7 could directly bind to the 3'-untranslated region of Kruppel-like factor 4 (KLF4, positions 574-580). Moreover, knockdown of KLF4 by the specific siRNA inhibited SH-SY5Y apoptosis under MPP(+) treatment. In addition, KLF4 overexpression apparently attenuated the protective effect of miR 7 in MPP(+)-induced SH-SY5Y apoptosis. This study indicated that miR-7 protects from MPP(+)-induced cell apoptosis in SH-SY5Y by directly targeting KLF4. PMID- 27003617 TI - Metal concentrations in Hydrocynus vittatus (Castelnau 1861) populations from a premier conservation area: Relationships with environmental concentrations. AB - Metals are known to have deleterious effects on aquatic ecosystems, so monitoring the bioaccumulation of these pollutants is important for the assessment of potential impacts. The aim of the study was therefore to determine the degree to which aquatic biota in selected rivers of the world renowned Kruger National Park (KNP) are exposed to metals entering from the catchments outside the KNP and to determine how these metal levels reflect what is occurring within the environment. Many of these rivers have never previously been assessed and those which have, have not been assessed within the past two decades. Tigerfish (Hydrocynus vittatus) is an economically important apex predator and was selected as the bioindicator for this study. Fish were sampled from the KNP sections of the Luvuvhu, Letaba and Olifants Rivers during the high and low flow periods from 2009 to 2011. The analysis of various metals from the aforementioned systems revealed spatial and temporal related variation in metal level patterns of the chosen bioindicator, with concentrations in fish from the Olifants River>Letaba River>Luvuvhu River and 2009>2010>2011. Although there were differences between rivers, metal concentrations were comparable and indicate that all of the studied KNP rivers, even those considered to be in a natural state are affected to some degree by anthropogenic activities. However, concentrations found during this study were much lower than previous studies in the area, as well as contaminated sites across the world, but were higher than concentrations in fish from contaminated sites in the Vaal River, South Africa. Bioaccumulated metals showed no correlation to metals in the water column, but some were correlated to sediment metal concentrations and the contamination and bioavailability of these metals within the sediments. This is of concern when managing the water resources of the conservation area since the contaminants enter the park from outside the borders and pose potential risks to the mandated conservation of aquatic biota within the KNP. PMID- 27003615 TI - Probing the Impact of Local Structural Dynamics of Conformational Epitopes on Antibody Recognition. AB - Antibody-antigen interactions are governed by recognition of specific residues and structural complementarity between the antigen epitope and antibody paratope. While X-ray crystallography has provided detailed insights into static conformations of antibody-antigen complexes, factors such as conformational flexibility and dynamics, which are not readily apparent in the structures, can also have an impact on the binding event. Here we investigate the contribution of dynamics in the HIV-1 gp120 glycoprotein to antibody recognition of conserved conformational epitopes, including the CD4- and coreceptor-binding sites, and an inner domain site that is targeted by ADCC-active antibodies. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was used to measure local structural dynamics across a panel of variable loop truncation mutants of HIV-1 gp120, including full length gp120, DeltaV3, DeltaV1/V2, and extended core, which includes DeltaV1/V2 and V3 loop truncations. CD4-bound full-length gp120 was also examined as a reference state. HDX-MS revealed a clear trend toward an increased level of order of the conserved subunit core resulting from loop truncation. Combined with biolayer interferometry and enzyme-linked immunosorbent assay measurements of antibody-antigen binding, we demonstrate that an increased level of ordering of the subunit core was associated with better recognition by an array of antibodies targeting complex conformational epitopes. These results provide detailed insight into the influence of structural dynamics on antibody-antigen interactions and suggest the importance of characterizing the structural stability of vaccine candidates to improve antibody recognition of complex epitopes. PMID- 27003618 TI - Triazole-based highly selective supramolecular sensor for the detection of diclofenac in real samples. AB - A triazole-based supramolecular chemosensor 6 for the selective spectrophotometric detection of diclofenac in human plasma and tap water was developed. The 6 was synthesized through click approach and characterized via UV vis spectroscopy, FT-IR, Mass and NMR spectroscopy. The supramolecular interaction of compound 6 with commonly used drugs has been investigated with the help of UV-vis spectral titrations, FT-IR and (1)H, (13)C NMR spectroscopy. The UV-visible spectral changes upon addition of various commonly used drugs showed that compound 6 is highly selective for diclofenac over other drugs. The supramolecule 6 exhibited a selective enhancement in the absorbance intensity after mixing with diclofenac in human plasma and water samples in the presence of other drugs at pH 6-7, with a linear range of 0.938 (R(2)=0.938) and a limit of detection 10uM. The relative standard deviation (RSD) for 100uM diclofenac was found to be 0.462. The Job's plot analysis revealed that diclofenac bind to compound 6 in 1:1 stoichiometry. PMID- 27003619 TI - Influence of Diaphragmatic Motion on Inferior Vena Cava Diameter Respiratory Variations in Healthy Volunteers. AB - BACKGROUND: The collapsibility index of inferior vena cava (cIVC) is widely used to decide fluid infusion in spontaneously breathing intensive care unit patients. The authors hypothesized that high inspiratory efforts may induce false-positive high cIVC values. This study aims at determining a value of diaphragmatic motion recorded by echography that could predict a high cIVC (more than or equal to 40%) in healthy volunteers. METHODS: The cIVC and diaphragmatic motions were recorded for three levels of inspiratory efforts. Right and left diaphragmatic motions were defined as the maximal diaphragmatic excursions. Receiver operating characteristic curves evaluated the performance of right diaphragmatic motion to predict a cIVC more than or equal to 40% defining the best cutoff value. RESULTS: Among 52 included volunteers, interobserver reproducibility showed a generalized concordance correlation coefficient (rhoc) above 0.9 for all echographic parameters. Right diaphragmatic motion correlated with cIVC (r = 0.64, P < 0.0001). Univariate analyses did not show association between cIVC and age, sex, weight, height, or body mass index. The area under the receiver operating characteristic curves for cIVC more than or equal to 40% was 0.87 (95% CI, 0.81 to 0.93). The best diaphragmatic motion cutoff was 28 mm (Youden Index, 0.65) with sensitivity of 89% and specificity of 77%. The gray zone area was 25 to 43 mm. CONCLUSIONS: Inferior vena cava collapsibility is affected by diaphragmatic motion. During low inspiratory effort, diaphragmatic motion was less than 25 mm and predicted a cIVC less than 40%. During maximal inspiratory effort, diaphragmatic motion was more than 43 mm and predicted a cIVC more than 40%. When diaphragmatic motion ranged from 25 to 43 mm, no conclusion on cIVC value could be done. PMID- 27003620 TI - Clinical Characteristics of Primary Vitreoretinal Lymphoma in an Indian Population. AB - PURPOSE: Primary vitreoretinal lymphomas (PVRL) pose a major diagnostic challenge, especially in the countries with a high prevalence of infectious variety of uveitis. The present study aims to report the clinical characteristics and diagnostic difficulties in patients with PVRL in an Indian Population. METHODS: Retrospective chart reviews of 12 patients with a diagnosis of PVRL. RESULTS: The study included 6 men and 6 women, with a mean age of 55.66 +/- 8.76 years. All had bilateral disease. The clinical signs included anterior uveitis (12 eyes; 50.0%); vitritis (18 eyes; 75%); vitreous clumps (16 eyes; 66.6%); subretinal deposits (11 eyes; 45.8%); retinal vasculitis (6 eyes; 25%); and optic disc swelling (2 eyes; 8.3%). The most commonly mistaken diagnosis was intraocular tuberculosis. The intraocular lesions responded to multiple intravitreal methotrexate injections. CONCLUSIONS: PVRL in India was likely to be mistaken for an infectious variety of uveitis. A high index of suspicion and thorough clinical examination is necessary to make the diagnosis. PMID- 27003621 TI - Flow cytometry and single nucleus sorting for Cre-based analysis of changes in transcriptional states. AB - The organs of eukaryotic organisms comprise complex interspersions of cell types, whose different molecular activities, and corresponding cellular states, cooperate during development to produce the final, functional organ. Dysfunction of organs in disease, particularly oncogenesis, initiates with changes of state of a minor subset of cells. It therefore is hard to detect early molecular indicators of disease within an overwhelming background of normal cells. Flow cytometry and sorting provides a convenient way to purify minority subpopulations, if a specific fluorophore can be unambiguously and exclusively associated with this subpopulation. We have generated a number of transgenic mouse lines expressing a nuclear-localized version of the Green Fluorescent Protein (GFP), within which the production of a chimeric histone 2B-GFP protein occurs under the control of a constitutively-active, actin-derived promoter, separated by a Floxed-STOP sequence. In the presence of Cre recombinase, within F1 progeny of these mouse lines, excision of the STOP sequence activates transcription which results in the emergence of cells containing green fluorescent nuclei. We describe the characterization of these lines using a combination of microscopic imaging, flow cytometry and sorting, and Reverse Transcription polymerase chain reaction of transcripts within single sorted nuclei isolated from tissue homogenates. These lines should be particularly useful for analysis of transcriptional changes in oncogenesis. (c) 2016 International Society for Advancement of Cytometry. PMID- 27003622 TI - The development and testing of a prototype mini-baghouse to control the release of respirable crystalline silica from sand movers. AB - Inhalation of respirable crystalline silica (RCS) is a significant risk to worker health during well completions operations (which include hydraulic fracturing) at conventional and unconventional oil and gas extraction sites. RCS is generated by pneumatic transfer of quartz-containing sand during hydraulic fracturing operations. National Institute for Occupational Safety and Health (NIOSH) researchers identified concentrations of RCS at hydraulic fracturing sites that exceed 10 times the Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (PEL) and up to 50 times the NIOSH Recommended Exposure Limit (REL). NIOSH research identified at least seven point sources of dust release at contemporary oil and gas extraction sites where RCS aerosols were generated. NIOSH researchers recommend the use of engineering controls wherever they can be implemented to limit the RCS released. A control developed to address one of the largest sources of RCS aerosol generation is the NIOSH mini-baghouse assembly, mounted on the thief hatches on top of the sand mover. This article details the results of a trial of the NIOSH mini-baghouse at a sand mine in Arkansas from November 18-21, 2013. During the trial, area air samples were collected at 12 locations on and around a sand mover with and without the mini baghouse control installed. Analytical results for respirable dust and RCS indicate the use of the mini-baghouse effectively reduced both respirable dust and RCS downwind of the thief hatches. Reduction of airborne respirable dust ranged from 85-98%; reductions in airborne RCS ranged from 79-99%. A bulk sample of dust collected by the baghouse assembly showed the likely presence of freshly fractured quartz, a particularly hazardous form of RCS. Planned future design enhancements will increase the performance and durability of the mini-baghouse, including an improved bag clamp mechanism and upgraded filter fabric with a modified air-to-cloth ratio. Future trials are planned to determine additional respirable dust and RCS concentration reductions achieved through these design changes. PMID- 27003623 TI - Determinants of Outcome in Burn ICU Patients with Septic Shock. AB - Infectious complications remain one of the most challenging concerns for the burn team. The goal of this study was to evaluate the diagnostic and therapeutic approaches and prognosis in burn patients with septic shock. This retrospective study included patients with severe burn injury who were admitted to a burn intensive care unit (ICU). Demographic and clinical data were recorded for each patient. The diagnostic and prognostic value of a number of clinical and laboratory parameters and various treatment options were evaluated. Sixty-four of the 378 patients (16.9%) were identified as having experienced a septic shock during ICU stay. The mortality rate of patients with septic shock was 46.9%. The main bacterial strains responsible for infection were Gram-negative bacteria (78.1%). Factors associated with outcome of septic shock on logistic regression analysis were presence of stage III of acute kidney injury (odds ratio [95% confidence interval] 2.03 [1.06-3.84]; P = 0.019), and lactate levels > 4 mmol/L during the first 48 hours of shock (odds ratio 1.92; 95% confidence interval: 1.02-3.62; P = 0.043). Prognosis of septic shock remains poor in burn patients with septic shock. The main causative pathogens of septic shock identified in our burn ICU were Gram-negative species. The main prognostic factors identified in this study were the presence of AKI, stage III, and high lactate levels early after the onset of septic shock. PMID- 27003624 TI - Changes in shape and cross-sectional geometry in the tibia of mice selectively bred for increases in relative bone length. AB - Limb bone size and shape in terrestrial mammals scales predictably with body mass. Weight-bearing limb bones in these species have geometries that enable them to withstand deformations due to loading, both within and between species. Departures from the expected scaling of bone size and shape to body mass occur in mammals that have become specialized for different types of locomotion. For example, mammals adapted for frequent running and jumping behaviors have hind limb bones that are long in relation to body mass, but with narrower cross sections than predicted for their length. The Longshanks mouse was recently established, a selectively bred line of mice with ~12-13% longer tibiae relative to body mass. This increased limb length resembles superficially the derived limb proportions of rodents adapted for hopping and jumping. Here, 3D geometric morphometrics and analyses of bone cross-sectional geometry were combined to determine whether selection for increased relative tibia length in Longshanks mice has altered the scaling relationship of size and shape, and/or bone robusticity, relative to the tibiae of random-bred control mice from the same genetic background. The results suggest that the Longshanks tibia is not a geometrically scaled version of the control tibiae. Instead, the Longshanks tibia has become narrower in cross-section in relation to its increased length, leading to a decrease in overall bending strength when compared with control tibiae. These changes in bone shape and robusticity resemble the derived morphology of mammals adapted for running and jumping, with important implications for the material properties and strength of bone in these mammals. PMID- 27003625 TI - Design and Evaluation Process of a Personal and Motive-Based Competencies Questionnaire in Spanish-Speaking Contexts. AB - Most questionnaires used for managerial purposes have been developed in Anglo Saxon countries and then adapted for other cultures. However, this process is controversial. This paper fills the gap for more culturally sensitive assessment instruments in the specific field of human resources while also addressing the methodological issues that scientists and practitioners face in the development of questionnaires. First, we present the development process of a Personal and Motive-based competencies questionnaire targeted to Spanish-speaking countries. Second, we address the validation process by guiding the reader through testing the questionnaire construct validity. We performed two studies: a first study with 274 experts and practitioners of competency development and a definitive study with 482 members of the general public. Our results support a model of nineteen competencies grouped into four higher-order factors. To assure valid construct comparisons we have tested the factorial invariance of gender and work experience. Subsequent analysis have found that women self-rate themselves significantly higher than men on only two of the nineteen competencies, empathy (p < .001) and service orientation (p < .05). The effect of work experience was significant in twelve competencies (p < .001), in which less experienced workers self-rate higher than experienced workers. Finally, we derive theoretical and practical implications. PMID- 27003626 TI - Systematic Analysis of Electrochemical CO2 Reduction with Various Reaction Parameters using Combinatorial Reactors. AB - Applying combinatorial technology to electrochemical CO2 reduction offers a broad range of possibilities for optimizing the reaction conditions. In this work, the CO2 pressure, stirring speed, and reaction temperature were varied to investigate the effect on the rate of CO2 supply to copper electrode and the associated effects on reaction products, including CH4. Experiments were performed in a 0.5 M KCl solution using a combinatorial screening reactor system consisting of eight identical, automatically controlled reactors. Increasing the CO2 pressure and stirring speed, or decreasing the temperature, steadily suppressed H2 production and increased the production of other reaction products including CH4 across a broad range of current densities. Our analysis shows that the CO2 pressure, stirring speed, and reaction temperature independently contributed to the limiting rate of CO2 supply to the electrode (Jlim). At a constant temperature, the limiting current density of CH4 increased proportionally with Jlim, illustrating that the production rate of CH4 was proportional to CO2 supply. Varying the CO2 pressure and stirring speed hardly affected the maximum Faradaic efficiency of CH4 production. However, changes to the reaction temperature showed a significant contribution to CH4 selectivity. This study highlights the importance of quantitative analysis of CO2 supply in clarifying the role of various reaction parameters and understanding more comprehensively the selectivity and reaction rate of electrochemical CO2 reduction. PMID- 27003628 TI - Ammonia stripping, activated carbon adsorption and anaerobic biological oxidation as process combination for the treatment of oil shale wastewater. AB - Anaerobic biodegradability of oil shale wastewater was investigated after the following pretreatment sequence: ammonia stripping and activated carbon adsorption. Anaerobic biological treatment of oil shale wastewater is technically feasible after stripping at pH 11 for reducing the N-NH3 concentration, adsorption with 5 g/L of activated carbon in order to reduce recalcitrance and pH adjustment with CO2 so that the sulphate concentration in the medium remains low. After this pretreatment sequence, it was possible to submit the wastewater without dilution to an anaerobic treatment with 62.7% soluble chemical oxygen demand removal and specific methane production of 233.2 mL CH4STP/g CODremoved. PMID- 27003627 TI - Can attention to the intestinal microbiota improve understanding and treatment of anorexia nervosa? AB - Anorexia nervosa (AN) is characterized by severe dietary restriction or other weight loss behaviors and exhibits the highest mortality rate of any psychiatric disorder. Therapeutic renourishment in AN is founded primarily on clinical opinion and guidelines, with a weak evidence base. Genetic factors do not fully account for the etiology of AN, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from AN. This review explores the relationship between the intestinal microbiota and AN and a potential role for this enteric microbial community as a therapy for this severe illness. PMID- 27003629 TI - Abuse in the Elderly-Cost Driver in a Health Care System? PMID- 27003630 TI - 2016 Rio Olympic Games: Can the schedule of events compromise athletes' performance? AB - The organizing committee of the 2016 Rio Olympic Games recently announced that some of the preliminary and final competitions will be held at night. The present article discusses the potential harmful effects of these late-night competitions on sleep, circadian rhythms and athletic performance during the Olympic Games. Specifically, night-time competition could lead to injury and may compromise an athlete's decision-making, attentional, physiological and other processes. Consequently, these impacts could negatively affect the performance of athletes and their teams. Thus, it is suggested that technical commissions take special care when creating strategies to minimize harm to the athletes by considering factors such as light exposure, melatonin intake, sleep hygiene and scheduled naps, and training at local competition time. Furthermore, it is necessary for specialists in chronobiology and sleep to engage with members of the national teams to develop an activity schedule for physical, technical, tactical and psychological preparation that accounts for circadian rhythms, thereby creating the best possible environment for the athletes to achieve their ideal performance. PMID- 27003631 TI - Analysis of Partition Functions for Metallocenes: Ferrocene, Ruthenocene, and Osmocene. AB - We present a calculation of the torsional potential of the three metallocenes of the iron group, that is, ferrocene, ruthenocene, and osmocene, calculated with the GAUSSIAN program suite. Both a variational method (through computation of the exact energy levels) and our Chebyshev imaginary time propagation method are used to calculate the hindered rotation partition function, demonstrating the efficiency of the Chebyshev scheme. The transition from a semirigid through a hindered rotor to the free rotor regime is demonstrated, and the effect of the hindered rotation (as opposed to a harmonic) treatment on the thermodynamics of metallocenes is demonstrated. PMID- 27003633 TI - The Impact of R-Optimized Administration Modeling Procedures on Brazilian Normative Reference Values for Rorschach Scores. AB - To generate normative reference data for the Rorschach Performance Assessment System (R-PAS), modeling procedures were developed to convert the distribution of responses (R) in protocols obtained using Comprehensive System (CS; Exner 2003 ) administration guidelines to match the distribution of R in protocols obtained using R-Optimized Administration (Meyer, Viglione, Mihura, Erard, & Erdberg, 2011 ). This study replicates the R-PAS study, examining the impact of modeling R Optimized Administration on Brazilian normative reference values by comparing a sample of 746 CS administered protocols to its counterpart sample of 343 records modeled to match R-Optimized Administration. The results were strongly consistent with the R-PAS findings, showing the modeled records had a slightly higher mean R and, secondarily, slightly higher means for Complexity and V-Comp, as well as smaller standard deviations for R, Complexity, and R8910%. We also observed 5 other small differences not observed in the R-PAS study. However, when comparing effect sizes for the differences in means and standard deviations observed in this study to the differences found in the R-PAS study, the results were virtually identical. These findings suggest that using R-Optimized Administration in Brazil might produce normative results that are similar to traditional CS norms for Brazil and similar to the international norms used in R-PAS. PMID- 27003634 TI - Temperature Dependence of the Surface and Volume Hydrophilicity of Hydrophilic Polymer Brushes. AB - The temperature-dependence of the volume and surface hydrophilicity of a series of water-swollen dense polymer brushes is measured by contact angle measurements in the captive bubble configuration, by ellipsometry, and by quartz crystal microbalance with dissipation monitoring (QCM-D). Thermoresponsive poly(N isopropylacrylamide) (PNIPAM) and poly(di(methoxyethoxy)ethyl methacrylate) (PMEO2MA), strongly hydrophilic poly(N,N-dimethylacrylamide) (PDMA) and poly(oligo(ethylene glycol) methacrylate) (POEGMA), and weakly hydrophilic poly(2 hydroxyethyl methacrylate) (PHEMA) brushes were synthesized by surface-initiated atom-transfer radical polymerization (SI-ATRP). Conditions leading to reproducible measurements of the contact angle are first provided, giving access to the surface hydrophilicity. Volume hydrophilicity is quantified by measuring the swelling of the brushes, either by QCM-D or by ellipsometry. A model-free methodology is proposed to analyze the QCM-D data. Comparison between the acoustic and optical swelling coefficients shows that QCM-D is sensitive to the maximal thickness of swollen brushes, while ellipsometry provides an integral thickness. Diagrams of surface versus volume hydrophilicity of the brushes finally lead to identify two types of behavior: strongly water-swollen brushes exhibit a progressive decrease of volume hydrophilicity with temperature, while surface hydrophilicity changes moderately; weakly water-swollen brushes have a close-to-constant volume hydrophilicity, while surface hydrophilicity decreases with temperature. Thermoresponsive brushes abruptly switch from one behavior to the other, and do not exhibit an abrupt change of surface hydrophilicity across their collapse transition contrarily to a common erroneous belief. In general, there is no direct correlation between surface and volume hydrophilicity, because surface properties are dependent on the details of conformation and composition at the surface, whereas volume properties are averaged over a finite region within the brush. PMID- 27003632 TI - Temporal Progression of Pneumonic Plague in Blood of Nonhuman Primate: A Transcriptomic Analysis. AB - Early identification of impending illness during widespread exposure to a pathogenic agent offers a potential means to initiate treatment during a timeframe when it would be most likely to be effective and has the potential to identify novel therapeutic strategies. The latter could be critical, especially as antibiotic resistance is becoming widespread. In order to examine pre symptomatic illness, African green monkeys were challenged intranasally with aerosolized Yersinia pestis strain CO92 and blood samples were collected in short intervals from 45 m till 42 h post-exposure. Presenting one of the first genomic investigations of a NHP model challenged by pneumonic plague, whole genome analysis was annotated in silico and validated by qPCR assay. Transcriptomic profiles of blood showed early perturbation with the number of differentially expressed genes increasing until 24 h. By then, Y. pestis had paralyzed the host defense, as suggested by the functional analyses. Early activation of the apoptotic networks possibly facilitated the pathogen to overwhelm the defense mechanisms, despite the activation of the pro-inflammatory mechanism, toll-like receptors and microtubules at the port-of-entry. The overexpressed transcripts encoding an early pro-inflammatory response particularly manifested in active lymphocytes and ubiquitin networks were a potential deviation from the rodent models, which needs further verification. In summary, the present study recognized a pattern of Y. pestis pathogenesis potentially more applicable to the human system. Independent validation using the complementary omics approach with comprehensive evaluation of the organs, such as lungs which showed early bacterial infection, is essential. PMID- 27003635 TI - Can Two-Dimensional Boron Superconduct? AB - Two-dimensional boron is expected to exhibit various structural polymorphs, all being metallic. Additionally, its small atomic mass suggests strong electron phonon coupling, which in turn can enable superconducting behavior. Here we perform first-principles analysis of electronic structure, phonon spectra, and electron-phonon coupling of selected 2D boron polymorphs and show that the most stable structures predicted to feasibly form on a metal substrate should also exhibit intrinsic phonon-mediated superconductivity, with estimated critical temperature in the range of Tc ~ 10-20 K. PMID- 27003640 TI - [Metabolic response to surgical stress and therapeutic perspectives]. AB - Perioperative patients usually suffer from metabolic response. This metabolic state is usually the result of some blend of response to partial starvation and to injury or specific diseases. Metabolic response to starvation and acute injury is inbuilt response to ensure maximal survival with a limited food intake. Yet, progressive loss of body tissue may have lethal consequences. Enhanced recovery after surgery is an optimized strategy of perioperative treatment based on variations of meta bolic state. It can reduce damage and acute injury, as well as facilitating early recovery after major surgery. PMID- 27003641 TI - [Application of enhanced recovery after surgery in minimally invasive colorectal surgery]. AB - ERAS combines modern anesthesia, pain control, and nutritional support technologies, and contains a series of evidence-based perioperative optimization measures, including preoperative preparation, intraoperative anesthesia and postoperative care, to reduce surgical stress and enhance recovery. Several clinical studies and meta-analysis have demonstrated that ERAS can accelerate postoperative rehabilitation in colorectal patients. In addition, minimally invasive colorectal surgery has the advantages of less trauma, less bleeding, and faster postoperative recovery, compared with open surgery. It has become the standard operation for colon resection. Recently 3D laparoscopic and robotic colorectal surgery, which overcomes limitations of conventional laparoscopic surgery, is increasingly used. Therefore, whether ERAS combined with minimally invasive colorectal surgery causes a cumulative advantage receives much concern. A number of studies and meta-analysis have demonstrated that ERAS combined with laparoscopic colorectal cancer surgery can shorten the length of hospital stay and reduce the incidence of complications, as the best perioperative plan for elective colorectal surgery. PMID- 27003643 TI - [Skills of using harmonic scalpel in laparoscopic surgery for colorectal cancer]. AB - Harmonic scalpel is an important instrument for laparoscopic surgery, and it can be used for dissection and hemostasis. During the procedure of laparoscopic surgery for colorectal tumor, surgeons can use Harmonic scalpel to identify the surgical plane around the mesorectum and mesocolon. We summarized technical points based on our own 15-year experiences of harmonic scalpel use in laparoscopic surgery for colorectal surgery, and extracts them into five words, which are 'shave, poke, cut, peel and push'. These skills are described in combination of the illustrations and videos in this article. PMID- 27003647 TI - [Preliminary exploration of right colectomy by laparoscopy-assisted surgery using three ports]. AB - OBJECTIVE: To explore the radicality, safety, feasibility and indication of right colectomy by laparoscopy-assisted surgery using three ports. METHODS: Clinical data of 109 patients undergoing laparoscopy-assisted right colectomy in the Ruijin Hospital from 2013 to 2014 were retrospectively reviewed. Patients were divided into triple-port group(n=65, 3 ports) and traditional group(n=44, 4 or 5 ports). In the triple-port group, 21 cases were converted, including 14 cases added an additional port, 4 cases added 2 ports and 3 cases converted to laparotomy. The radicality, safety and feasibility were compared between the two groups. Difficulty of the triple-port procedure was summarized and the indication was concluded. RESULTS: No significant differences were observed in specimen length, number of harvested lymph node, CME rate, time to resume fluids, postoperative hospital stay, morbidity of complication, reoperation rate, operation time, blood loss and incidental bowel damage between the two groups (all P>0.05). Among triple-port group, body mass index(BMI) and history of previous surgery were significantly different between those succeed and failed in the procedure [(22.4+/-2.9) kg/m(2) vs. (25.4+/-3.8) kg/m(2), P=0.001; 22.7%(10/44) vs. 47.6%(10/21), P=0.017], while other factors were not significantly different(all P>0.05). CONCLUSIONS: For right-colectomy, triple port and traditional laparoscopic procedures are comparable in terms of oncologic clearance, safety and feasibility. In selection of suitable patients for the triple-port procedure, BMI and history of previeus surgery should be considered. PMID- 27003642 TI - [Key points and difficulties in implementing enhanced recovery after surgery of colorectal cancer]. AB - Enhanced recovery after surgery (ERAS), a hotspot of modern surgery, aims to make patients get early recovery of physical and psychological condition from surgical injury through reducing interference of inner-equilibrium. Our center has carried out fast track multi-disciplinary treatment (FTMDT) trail of colorectal cancer since 2009. This paper discusses the key points and difficulties in implementing ERAS for colorectal cancer from the association between ERAS and shortening of hospital stay, the idea renewal of medical staff and comprehensive therapy mode based on our experience and current situations in China. PMID- 27003638 TI - [Current Status of Enhanced Recovery After Surgery in China]. AB - ERAS (enhanced recovery after surgery) has made significant progress since it was first introduced into China a decade ago. Series of studies on ERAS has been carried out in Jinling Hospital, Nanjing University, and brought out many exciting achievements for gastrointestinal cancer surgery. Merely in the year of 2015, advance in ERAS has been achieved in China. The first ERAS Group in China was founded. The first China ERAS Congress was inaugurated in 2015, publishing several Chinese Experts consensuses on ERAS clinical practice. All these show that ERAS are gradually brought to the attention of the Chinese surgeons and their active participation. It is believed that ERAS will have a promising future in China. PMID- 27003646 TI - [Application of transperineal single-port access assisted extralevator abdominoperineal excision in low rectal cancer]. AB - OBJECTIVE: To explore the feasibility and safety of transperineal single-port laparoscopy assisted exralevator abdominoperineal excision(TPSP-ELAPE). METHODS: Three cases (2 males and 1 female) who underwent TPSP-ELAPE at lithotomy position in the Peking University People's Hospital from January to February 2016 were analyzed retrospectively. The mean age was(55.3+/-7.2) years. Mean body mass index (BMI) was (23.0+/-1.3) kg/m(2). Mean distance between tumor and anal verge was (1.8+/-0.3) cm. Abdominal procedure was done firstly and then perineal procedure under lithotomy position. Abdominal procedure was performed by routine laparoscopy with 5 trocars. TPSP-ELAPE procedure was performed in perineal procedure. The perineal defect was closed by purse string, followed by spindle incision around the anus. Perianal skin and subcutaneous tissue was dissected until the junction between extra anal sphincter and levator ani muscle under direct vision. Perineal skin was sutured with double purse string by 2-0 prolene, and single port canal was placed inside in order to close perineal defect. The pneumoperitoneal pressure was set to 10 mmHg and laparoscopy and instrument was placed through the single-port canal. Space between isochioanal fossa and levator ani muscle was exposed by the contraction of laparoscopic clam. Lateral and posterior side was mobilized firstly. The anterior was dissected under the help of vaginal examination and contraction by abdominal group. The levator ani muscle was divided near the initial site, and negative resection margin was confirmed in the operation. Specimen was exteriorized through the perineum. RESULTS: The mean intraoperative blood loss of three cases was (123.3+/-25.2) ml. The total operative time was (296.7+/-25.1) minutes. The time used by the perineal group was (196.7+/-20.8) minutes. The volume of drainage was (39.0+/-10.1) ml at the third day after operation. The time to first stoma output was (2.3+/-0.6) days. The perineal drainage removal time was (7.7+/-0.6) days. The circumferential resection margins were negative in all specimens, and there were no perioperative complications. CONCLUSION: TPSP-ELAPE is feasible and safe, which could avoid turning over the patient and facilitate anesthesia. It follows the anatomic plane of open ELAPE procedure with minimally invasive advantage. PMID- 27003636 TI - Synthesis and Biological Evaluation of Novel sigma1 Receptor Ligands for Treating Neuropathic Pain: 6-Hydroxypyridazinones. AB - By use of the 6-hydroxypyridazinone framework, a new series of potent sigma1 receptor ligands associated with pharmacological antineuropathic pain activity was synthesized and is described in this article. In vitro receptor binding studies revealed high sigma1 receptor affinity (Ki sigma1 = 1.4 nM) and excellent selectivity over not only sigma2 receptor (1366-fold) but also other CNS targets (adrenergic, MU-opioid, sertonerigic receptors, etc.) for 2-(3,4-dichlorophenyl) 6-(3-(piperidin-1-yl)propoxy)pyridazin-3(2H)-one (compound 54). Compound 54 exhibited dose-dependent antiallodynic properties in mouse formalin model and rats chronic constriction injury (CCI) model of neuropathic pain. In addition, functional activity of compound 54 was evaluated using phenytoin and indicated that the compound was a sigma1 receptor antagonist. Moreover, no motor impairments were found in rotarod tests at antiallodynic doses and no sedative side effect was evident in locomotor activity tests. Last but not least, good safety and favorable pharmacokinetic properties were also noted. These profiles suggest that compound 54 may be a member of a novel class of candidate drugs for treatment of neuropathic pain. PMID- 27003644 TI - [Nutritional support for critical ill patients in gastrointestinal surgery]. AB - Nutrition support is an important part of the comprehensive treatment for the critically ill patients with the pathophysiology changes of stress responses related to hypercatabolism, immunity inflammatory reaction disordered and organ dysfunction. Compared with other critical illness, gastrointestinal surgical critically ill patients have the complex characteristics of altered gastrointestinal anatomy and (or) function. Therefore, the nutritional support especially the enteral nutrition support for critical illness patients in gastrointestinal surgery is more difficult and demanding. Mastering the principles, including the timing, route, type and amount of nutrients delivered, and developing an individualized nutritional plan according to the patient's own characteristics, may help to improve its safety and tolerance. Early nutrition support, especially early enteral nutrition, can reduce complications and mortality, enhance recovery and improve outcome for gastrointestinal surgical severely ill patients. PMID- 27003645 TI - [Application of enhanced recovery after surgery for patients with laparoscopic radical gastrectomy]. AB - OBJECTIVE: To investigate the clinical application effects of enhanced recovery after surgery (ERAS) during perioperative period on patients undergoing laparoscopic radical gastrectomy. METHODS: A total of 127 patients with gastric cancer receiving laparoscopic radical gastrectomy in our department from July 2013 to February 2015 were prospectively enrolled. Patients were randomly divided into ERAS group (n=67) treated with ERAS method and conventional group (n=60) treated with the traditional perioperative management. The perioperative efficacy and postoperative short-term outcomes were compared between the two groups. RESULTS: All the patients were recovery with no mortality during perioperative period. Compared with conventional group, patients in ERAS group showed shorter time of nasogastric tube placement[(1.4+/-0.6) days vs. (2.2+/-0.6) days, P=0.000], shorter time to first flatus [(3.2+/-0.9) days vs. (3.8+/-1.1) days, P=0.004], shorter time to first ambulation [(2.3+/-1.1) days vs. (4.2+/-6.4) days, P=0.026], shorter time to initiate oral intake (1.9+/-0.7) days vs. (4.0+/ 1.1) days, P=0.000] and shorter postoperative hospital stay [(13.9+/-4.0) days vs. (18.7+/-9.1) days, P=0.000]. Visual pain scores were all significantly lower in the ERAS group as compared to the traditional group 2 hours after anesthesia awakening, 12, 24, 48 hours after operation and at the first ambulation respectively(all P<0.05). The overall complication rate was significantly lower in ERAS group than that in conventional group[14.9%(10/67) vs. 30.0%(18/60), P = 0.041]. Patients in the ERAS group had shorter postoperative hospital stay [(13.9+/-4.0) days vs. (18.7+/-9.1) days, P=0.000]. CONCLUSION: ERAS during perioperative period in laparoscopic radical gastrectomy is safe and effective, which is associated with quicker postoperative rehabilitation, better pain control and shorter hospital stay. PMID- 27003639 TI - [Enhanced recovery after surgery based on medical ethics]. AB - Enhanced recovery after surgery (ERAS), a new model of perioperative management developed in recent years, can shorten hospital stay, reduce medical cost and postoperative discomfort. However, some of these measures under the strategy are negation of the traditional recommendation and many surgeons are concerned about the medical tangle by the complications coming with the ERAS strategy. In this paper, ERAS strategy is evaluated from an ethical standpoint and the assessment factors of medical behavior are introduced based on medical virtues and medical ethnics. It is also analyzed that how to deal with the conflicts between the textbooks and the ERAS strategy, and elaborated that the medical ethics should be observed if the ERAS strategy is implemented. The scientific principles must be followed, the rights and interests of the patients need to be protected, and the informed consent should be guaranteed. PMID- 27003648 TI - [Clinical application of curved cutter stapler in laparoscopic anterior resection of low rectal cancer]. AB - OBJECTIVE: To make a preliminary assessment of the feasibility of Endo GIATM Radial Reload with Tri-StapleTM Technology(Radial Reload) in laparoscopic anterior resection of low rectal cancer. METHODS: Clinical data of 21 low rectal cancer patients undergoing laparoscopic anterior resection with the Radial Reload in our department between July 2014 and July 2015 were retrospectively analyzed. RESULTS: All the rectums were achieved complete transection by the first stapler device firing and all the operations were performed successfully. No patient were converted to open surgery. The operative time ranged from 110.0 to 180.0(140.5+/ 16.6) minutes, the blood loss ranged from 50.0 to 100.0(66.8+/-11.4) ml, and the distal resection margin ranged from 1.0 to 3.0(1.8+/-0.7) cm. Tumor cells were not discovered in all the postoperative pathological samples of distal resection margin. Among 21 cases, stage I( was found in 14 cases, stage II( in 4 cases and stage III( in 3 cases. There were no anastomotic bleeding and anastomotic leakage. There was no local recurrence and distant metastasis during a median follow-up of 6 months(1 to 13 months) postoperatively. CONCLUSION: The application of Radial Reload in laparoscopic anterior resection of low rectal cancer is feasible with satisfactory efficacy. PMID- 27003649 TI - [Analysis of prognostic factors of 110 patients with metastatic ovarian tumors from gastric cancer]. AB - OBJECTIVE: To explore the clinicopathalogical features, treatment methods and prognostic factors of metastatic ovarian tumors from gastric cancer. METHOD: Clinical data of 110 gastric cancer patients with metastatic ovarian tumor between January 2001 and August 2015 of Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Univariate and Cox regression model multivariate analyses were performed to investigate the risk factors of metastatic ovarian tumor from gastric cancer. RESULT: The follow-up duration ranged from 3 to 60 months (mean 12 months). The follow-up rate was 94.5%(104/110). 104 cases underwent surgical treatment, including satisfactory cytoreductive surgery (57 cases) and unsatisfactory cytoreductive surgery (47 cases). The median overall survival was 12 months and median progression-free survival was 8 months. The survival rates of 1-, 3- and 5-year were 48.1%, 7.7% and 0, respectively. Univariate analysis revealed that pattern of metastasectomy, number of metastatic lymph node, cytoreductive surgery level, presence of peritoneal metastasis or not when ovarian metastasis was diagnosed, ovariectomy prior to primary gastric cancer and extent of ovarian metastatic lesion were associated with prognosis(P<0.05). Multivariate analysis revealed that extent of ovarian metastatic lesion(RR=2.76, 95% CI: 1.68 to 4.54, P=0.005), presence of peritoneal metastasis when ovarian metastasis was diagnosed (RR=0.21, 95% CI: 0.11 to 0.41, P=0.003) and cytoreductive surgery level(RR=3.67, 95% CI: 2.13 to 6.33, P=0.011) were independent prognostic factors. CONCLUSIONS: Prognosis of patients with metastatic ovarian carcinoma from gastric cancer is quite poor. Extent of ovarian metastatic lesion and peritoneal metastasis were independent prognostic factors. Optimal cytoreduction is associated with better survival. PMID- 27003637 TI - Maternal blood pressures during pregnancy and the risk of delivering a small-for gestational-age neonate. AB - OBJECTIVE: To determine the relationship between maternal blood pressures throughout pregnancy and the risk of delivering a small-for-gestational-age (SGA) neonate. METHODS: Women were prospectively enrolled at 9-14 weeks and had serial blood pressure measurements throughout pregnancy. SGA prevalence was compared to maternal blood pressure at enrollment, average blood pressure during each trimester, and blood pressure trends throughout gestation. Blood pressure was categorized as normotension, prehypertension, or hypertension using Joint National Committee on Hypertension-7 (JNC-7) definitions. Information on preeclampsia prevalence was also obtained due to its frequent concurrence with SGA. RESULTS: A total of 758 women had 8438 blood pressure measurements taken (average 11.1, range 3-14) and 65 (8.6%) delivered an SGA neonate. Forty-two of 514 (8.2%) normotensive women at enrollment and 23/244 (9.4%) women with enrollment prehypertension or hypertension delivered an SGA neonate. Women with persistent hypertensive range blood pressures had an SGA rate 2-3 times higher than other women (p = 0.272) as well as a significantly higher preeclampsia rate (p < 0.001). Women with elevated enrollment blood pressures did not have an increased SGA rate if their blood pressures improved throughout pregnancy. Logistic regression identified enrollment uterine artery Doppler, pregnancy associated plasma protein-A levels, and ethnicity as primary contributors to SGA. CONCLUSION: Blood pressure improvement throughout pregnancy decreases the preeclampsia rate without increasing SGA frequency. Theoretical risks of fetal growth delay should not prevent investigations into improved maternal blood pressure control, possibly at thresholds lower than commonly used in obstetric practice, beginning in the first trimester of pregnancy. PMID- 27003650 TI - [Application value of combined organ radical resection in patients with recurrent gastric cancer]. AB - OBJECTIVE: To investigate the outcomes after combined organ radical resection for the recurrent gastric cancer. METHODS: Complete clinicopathological data of 48 recurrent gastric cancer patients who received radical resection before and underwent reoperation again in the Sun Yat-sen Memorial Hospital and The Second Affiliated Hospital of Xinjiang Medical University from January 2008 to December 2013 were analyzed retrospectively. Of 48 patients, 32 received combined organ radical resection(radical group) and 16 received combined organ palliative gastric stump resection (palliative group). RESULTS: In the radical group, one case(3.1%,1/32) died 5 days after operation due to hepatorenal syndrome and 9 had postoperative complications (28.1%,9/32), including external intestinal fistula, pancreatic fistula, biliary fistula and anastomotic bleeding. In the palliative group, only one patient(6.2%, 1/16) had postoperative pneumonia and partial intestinal obstruction, with lower complication morbidity as compared to the radical group(P<0.05). The median survival time was significantly longer in the radical group(36.0 vs. 11.5 months, P<0.01). The 1- and 3-year survival rates were 93.1%, 72.4% in the radical group, and 31.3%, 18.8% in palliative group, whose differences were statistically significant. Multivariate Cox regression analysis showed that clinical stage (HR:3.106, 95% CI:1.357-6.321, P=0.008), peritoneal metastasis (HR:10.167, 95% CI:3.230-35.234, P=0.000) and radical cure situation(HR:3.256, 95% CI:1.267-9.389, P=0.009) were independent prognostic factors. CONCLUSION: The combined organ radical resection can provide better survival for recurrent gastric cancer patients, while the indications should be controlled strictly with preoperative multidisciplinary assessment and precise surgical judgment in order to decrease the complication. PMID- 27003652 TI - [Analysis of associated factors of extramural venous invasion detected by CT scan in gastric cancer]. AB - OBJECTIVE: To investigate the ability of contrast enhanced multiple-row detector computed tomography(ceMDCT) in the determination of extramural venous invasion (EMVI) in patients with gastric cancer and to analyze associated factors of EMVI. METHODS: From January 2009 to December 2013, 253 patients with gastric cancer undergoing ceMDCT in Peking University People's Hospital were included in this study. The imaging characteristics and clinical data were retrospectively reviewed. Positive or negative EMVI on ceMDCT(ctEMVI) was determined according to the EMVI scores criteria defined by MR high resolution image of rectal cancer. Chi-square test was used to analyze the associations of ctEMVI with other images and clinicopathological data. RESULTS: The positive rate of ctEMVI was 32.8%(83/253) according to the EMVI scores criteria. Positive ctEMVI was associated with following CT findings, such as ctT (chi(2)=46.848, P=0.000), ctN (chi(2)=41.095, P=0.000), ctM (chi(2)=23.864, P=0.000), tumor growth pattern (chi(2)=8.580, P=0.003), tumor sizes (chi(2)=21.177, P=0.000), and with pathological T staging (chi(2)=28.994, P=0.000) and N staging (chi(2)=28.671, P=0.000), while no association with age, gender, histological type and tumor differentiation were seen(all P>0.05). CONCLUSIONS: ceMDCT can be used to detect ctEMVI in patients with gastric cancer. ctEMVI is associated with invasion depth, lymph node metastasis, distant metastasis, tumor size, tumor location and growth pattern. PMID- 27003651 TI - [Effect of body mass index on postoperative outcomes in patients with gastric cancer]. AB - OBJECTIVE: To explore the effect of body mass index (BMI) on postoperative short term prognosis and survival rate of gastric cancer patients. METHODS: Clinical and follow-up date of 153 gastric cancer cases undergoing radical operation in our hospital from January to June 2010 were retrospectively analyzed. According to BMI, patients were divided into low group (BMI<18.5, 23 cases), normal group (18.5<=BMI<25.0, 95 cases) and high group (BMI>=25.0, 35 cases). Clinicopathological features and outcomes were compared the among three groups. RESULTS: Among three groups, the differences in operation time, intraoperative blood loss, number of lymph node retrieved, postoperative hospital stay, lymph node metastasis rate, tumor staging and postoperative complication morbidity were not statistically significant (all P>0.05). Preoperative hemoglobin in the low group was significantly lower as compared to normal and high groups [(106.1+/ 13.8) g/L vs. 113.5+/-5.2) g/L and (123.5+/-8.7) g/L, F=3.265, P=0.041], and so was the preoperative albumin [(38.7+/-2.5) g/L vs. (41.3+/-0.8) g/L and (43.5+/ 1.4) g/L, F=8.516, P=0.000]. The ratio of gastric cardiac cancer in the low group was significantly lower as compared to the normal and high groups[34.8%(8/23) vs. 68.4%(65/95) and 62.9%(22/35), chi(2)=8.913, P=0.012]. Five-year survival rate of the low, normal and high groups were 43.5%, 50.5% and 65.7% respectively(P=0.189). Subgroup analysis showed that the 5-year survival rate of patients with gastric cardiac cancer in the low group was significantly lower as compared to those in the high group (25.0% vs. 84.6%, P=0.004). CONCLUSIONS: BMI dose not generally play a role in short-term outcomes and long-term survival of the gastric cancer patients. Nutritional improvement and body weight maintenance may be beneficial to low BMI patients, especially those with gastric cardiac cancer. PMID- 27003653 TI - [Self-control study of dynamic multiple pelvic angiography and pelvic four contrast defecography in the diagnosis of functional defecation disorder]. AB - OBJECTIVE: To evaluate and compare the value of dynamic multiple pelvic angiography and pelvic four-contrast defecography in the diagnosis of functional defecation disorder. METHODS: From September 2014 to July 2015, a prospective controlled trial was carried out in Chengdu Anorectal Hospital. A total of 32 patients met the inclusion criteria of functional defecation disorder simultaneously underwent pelvic four-contrast defecography and dynamic multiple pelvic angiography. The diagnostic results of these two methods were compared. RESULTS: The absolute values of anorectal angle and level of perineum, peritoneum and bladder from rest to defecation were (29.6+/-13.6) degrees , (26.2+/-14.2) mm, (55.5+/-25.6) mm and (28.9+/-16.5) mm in dynamic multiple pelvic angiography, and (24.6+/-5.8) degrees (18.7+/-10.6) mm, (34.5+/-18.4) mm and (19.2+/-11.8) mm in pelvic four-contrast defecography respectively, whose differences were statistically significant (P = 0.026, 0.022, 0.000, 0.011 respectively). The diagnostic rate of pelvic peritoneal hernia was 93.8%(30/32) and 68.8%(22/32) in dynamic multiple pelvic angiography and pelvic four-contrast defecography respectively with significant difference(P=0.011). CONCLUSION: Dynamic multiple pelvic angiography has significant advantage in the diagnosis of pelvic peritoneal hernia, and can provide a more objective basis for the diagnosis of functional defecation disorder. PMID- 27003654 TI - [Preoperative evaluation of multi-slice spiral computed tomography angiography in laparoscopic radical operation for colorectal carcinoma]. AB - OBJECTIVE: To investigate the clinical application of 256 multi-slice spiral computed tomography angiography (MSCTA) technique in the preoperative evaluation of mesenteric angiography in order to provide a reference to vessel anatomy and dissociation in laparoscopic radical operation for colorectal carcinoma. METHODS: Clinical data of 50 patients with colorectal cancer who underwent preoperative MSCTA+FDCT and laparoscopic curative operation at our hospital from October 2013 to March 2015 were collected (MSCTA group). The evaluation item was visualization of mesenteric artery, which was compared with the findings under laparoscopic surgery. Meanwhile, another 50 colorectal cancer patients undergoing laparoscopic radical operation by the same surgeon team without preoperative MSCTA examination were used as control(control group). Clinical data were compared between the two groups. RESULTS: MSCTA precisely and correctly demonstrated anatomy and variations of the mesenteric artery and relative nutrient vessel in carcinoma. The angiography reconstruction images were consistent with the visual anatomy and variation from laparoscopic findings, whose diagnostic conformity rate of 100%. As compared to control group, operative time was shorter [(195.0+/-23.2) minutes vs.(218.0+/-19.6) minutes, t=8.326, P=0.015], and blood loss was less[(168.1+/ 18.8) ml vs. (206.5+/-14.3) ml, t=-19.369, P=0.002] in MSCTA group. Differences of number of harvested lymph node, postoperative complication morbidity, postoperative hospital stay and hospitalization cost were not significant between two groups(all P>0.05). CONCLUSION: Preoperative MSCTA can demonstrate anatomy and variations of the mesenteric artery precisely and correctly, thus it is beneficial to shorten the operation time and to reduce blood loss. PMID- 27003656 TI - [Screen and identification of serum protein biomarkers in gastric cancer]. AB - OBJECTIVE: To screen and identify the serum specific protein markers of patients with gastric cancer by proteomics technology, and to provide more comprehensive serum protein fingerprint model for the early diagnosis of gastric cancer. METHODS: Preoperative and postoperative blood samples were collected from 60 gastric cancer patients. Mass spectrometry (SELDI-TOF-MS) technology was used to detect and screen serum specific proteins in gastric cancer patients(preoperative group, postoperative group, metastasis group), and the result was compared with normal control group. Gel electrophoresis(TRICINE SDS-OAGE) technology was applied in the separation and purification for those different protein. Matrix assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF) technology was used in the identification for the proteins following separation and purification. RESULT: Mass spectrometry data of preoperative group and normal group resulted in 15 specific m/z peak(P<0.01). SVM screened by a combination of the highest index model Youden get m/z peak at 6 449.1 protein markers. The protein expression of preoperative group was significantly higher than that of normal group(2 299.3+/-2 029.3 vs. 509.5+/ 168.3, P<0.01). Mass spectrometry data of preoperative group and postoperative group resulted in 6 specific m/z peak(P<0.01). SVM screened by a combination of the highest Youden index model indentified get m/z peak at 6 449.2 protein markers. The protein expression of preoperative group was significantly higher than that of postoperative group(1 247.9+/-685.0 vs. 476.5+/-157.8, P<0.01). Mass spectrometry data of preoperative group and metastasis group resulted in 12 specific m/z peak (P<0.01). SVM screened by a combination of the highest Youden index model indentified get m/z peak at 6 448.9 protein markers. The protein expression of metastasis group was higher than that of preoperative group(1 506.9+/-1 036.5 vs. 649.7+/-621.0). MALDI-TOF/TOF identified that the protein with m/z peak at 6 449 was Apo CIII(. CONCLUSION: Apo CIII( may be the specific serum protein marker of gastric cancer, which may provide a more comprehensive serum protein fingerprint model for the early diagnosis of gastric cancer and a new way for further research. PMID- 27003658 TI - [Robotic versus laparoscopic gastrectomy for gastric cancer: a meta-analysis]. AB - OBJECTIVE: To compare the clinical efficacy with meta-analysis between robot assisted gastrectomy(RAG) and laparoscopy-assisted gastrectomy (LAG) for gastric cancer. METHODS: A literature search was performed in PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CNKI(Chinese National Knowledge Infrastructure), and CBM(China Biological Medicine) databases for clinical researches published before July 2015 that compared RAG with LAG. Operative time, estimated blood loss, harvested lymph nodes, proximal margin, distal margin, hospital stay, conversion and complications were compared using weighted mean differences(WMD) and odds ratios (OR). RESULTS: Sixteen studies were included in the analysis, comprising 5 764 patients(1 593 RAGs, 4 171 LAGs). RAG was associated with longer operative time (WMD=49.68, 95% CI: 35.54 to 63.82, P=0.000), less estimated blood loss (WMD=-26.10, 95% CI: -42.90 to -9.31, P=0.002), and shorter hospital stay(WMD=-0.72, 95% CI: -1.35 to -0.09, P=0.024). Conversion, mortality, complications, proximal margin, distal margin and harvested lymph nodes of RAG were similar to LAG. In meta-analysis results of distal gastrectomy and early-stage gastric cancer, RAG had more harvested lymph nodes (distal gastrectomy: WMD=2.23, 95% CI: 0.33 to 4.13, P=0.021; early-stage gastric cancer: WMD=2.58, 95% CI: 1.05 to 4.12, P=0.001). CONCLUSIONS: RAG can be performed safely with less estimated blood loss and more harvested lymph nodes as compared to LAG. Radical resection can be achieved by RAG. PMID- 27003657 TI - [Establishment and comparison of stoma and stoma-free heterotopic small intestine transplantation models in mice]. AB - OBJECTIVE: To establish stoma and stoma-free murine models of heterotopic small intestine transplantation in order to choose a more effective and reliable model. METHODS: A total of 140 male 8-10 weeks age C57BL/6(B6) mice weighted 25-30 g were enrolled in the experiment. Syngeneic heterotopic small intestine transplantation was performed between C57BL/6 mice, and recipient mice were divided into either stoma or stoma-free group. Heterotopic small intestine transplantation was performed in 70 mice, with 35 mice in each group. After closing the proximal end of the graft by ligation, the distal end of graft was exteriorized as a stoma then secured to the skin of the abdominal wall in stoma group. In stoma-free group, the distal end of graft was anastomosed end-to-side to the recipient ileum. Successful rate of operation, two-week survival rate, operation time, associated complications, postoperative care time and body weight change were recorded and compared between two groups. RESULTS: The successful rate of stoma group was 65.7%, while it was 80.0% of stoma-free group (chi(2)=1.806, P=0.179). The operation time of donor in stoma group was (48.1+/ 6.6) minutes, while it was (47.2+/-5.9) minutes in stoma-free group (t=0.598, P=0.552). The operation time of recipient in stoma group was (77.9+/-9.1) minutes, while it was (76.4+/-8.3) minutes in stoma-free group (t=0.683, P=0.497). The cold ischemic time of graft in stoma group was (34.7+/-4.0) minutes, while it was (33.9+/-4.6) minutes in stoma-free group(t=0.667, P=0.507). The two-week survival rate of stoma group was 45.7%, and it was 77.1% of stoma free group(chi(2)=7.295, P=0.007). The stoma group had more complications[54.3%(19/35) vs. 22.9%(8/35), chi(2)=7.295, P=0.007], which needed more postoperative care time(191 min vs. 35 min). The weight loss in stoma group in the third day after operation was more significant [(81.52+/-5.20)% vs. (85.46+/-4.65)%, t=2.856, P=0.006]. By 2 weeks after operation, the weight of mice in both groups retruned to 95% of the postoperative wight. CONCLUSION: The murine heteropotic small intestine transplantation model with stoma-free appears to be more reasonable and reliable. PMID- 27003659 TI - [Meta-analysis of relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer]. AB - OBJECTIVE: To investigate the relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer. METHODS: The literatures on extranodal tumor deposits and postoperative survival rate in patients with colorectal cancer published at home and abroad from 1990 to 2014 were retrieved in 15 English literature databases such as MEDLINE/PubMed, Web of Science, Directory of Open Access Journals(DOAJ), SpringerLink and Chinese literature databases such as Chinese Biomedical Literature Database CD-ROM, China National Knowledge Infrastructure (CNKI) Database with the internet platform of Yonsei University Library. After screening for inclusion, data extraction and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. RESULTS: There were 10 studies meeting the inclusion criteria for meta-analysis. The total sample size of the studies was 4 068 cases with ENTD(+) 727 cases, while ENTD(-) 3 341 cases. Meta analysis showed that 5-year overall survival rate and 5-year relapse-free survival rate were significantly lower in ENTD(+) group than those in ENTD(-) group (OR 0.27, 0.23; 95% CI:0.18 to 0.43, 0.16 to 0.34 respectively, both P=0.000); the 5-year overall survival rates were both significantly lower in ENTD(+) group as compared to ENTD(-) group for patients with N0 and N(+) colorectal cancer (both P<0.05). CONCLUSION: Extranodal tumor deposits is a poor prognostic factor of patients with colorectal cancer. PMID- 27003655 TI - [Effect of Roux-en-Y gastric bypass on the short-term immune function in patients with type 2 diabetes mellitus]. AB - OBJECTIVE: To investigate the effect of laparoscopic Roux-en-Y gastric bypass on the short-term immune function of type 2 diabetic patients and to explore the correlation between the immune regulatory effect and blood glucose control. METHODS: Clinical data of 28 patients with type 2 diabetes mellitus who underwent laparoscopic Roux-en-Y gastric bypass surgery in our hospital during January 2014 to January 2015 were retrospectively collected. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), immunoglobulin (IgG, IgA, IgM), T lymphocytes CD3(+), killer T cells CD3(+)CD8(+), helper T cells CD3(+)CD4(+), natural killer(NK) cell subsets CD16(+),CD56(+) and B cell subsets CD19(+),CD45(+) levels were detected and compared between before and after surgery. Correlation of immunoglobulin and immune cell subsets with the level of FBG and HbA1c were examined. RESULTS: After operation, FBG and HbA1c decreased significantly from (5.78+/-1.15) mmol/L to (14.21+/-1.89) mmol/L, and (9.96+/-0.97)% to (6.87+/ 0.69)%, respectively (all P<0.05), and immunoglobulin (IgG, IgA, IgM) increased significantly [IgG: from(9.41+/-1.23) g/L to (12.74+/-1.61) g/L, IgM: from (1.71+/-0.22) g/L to (2.43+/-0.39) g/L, IgA: from (1.25+/-0.26) g/L to (1.97+/ 0.23) g/L, all P<0.05]. Besides, T lymphocytes CD3(+), killer T cells CD3(+)CD8(+) and B cell subsets CD19(+)CD45(+) elevated significantly as well [T lymphocytes CD3(+): from (55.3+/-3.8)% to (67.6+/-4.6)%, killer T cells CD3(+)CD8(+): from (15.6+/-5.3)% to (28.7+/-4.2)%, B cell subsets CD19(+)CD45(+): from (8.4+/-3.7)% to (18.1+/-4.1)%, respectively, all P <0.05]. There was no significant difference in the expression of helper T cells CD3(+)CD4(+) and natural killer cell subsets CD16(+)CD56(+) between pre-operation and post operation(all P>0.05). Levels of immunoglobulin (IgG, IgA, IgM), CD4(+)/CD8(+) ratio and B cell subsets were negatively correlated with HbA1c and FBG levels (IgG with FBG: r=-0.865, IgA with FBG: r=-0.887, IgM with FBG: r=-0.902, CD4(+)/CD8(+) with FBG: r=-0.956, CD19(+)CD45(+) with FBG: r=-0.834; IgG with HbA1C: r=-0.859, IgA with HbA1C: r=-0.957, IgM with HbA1C: r=-0.843, CD4(+)/CD8(+) with HbA1C: r=-0.912, CD19(+)CD45(+) and HbA1C: r=-0.885, all P<0.05), but the proportion of NK cells was not significantly correlated with HbA1c and FBG (P>0.05). CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass has good effect on the immune function of patients with type 2 diabetes mellitus. Improvement of immune function is correlated with the control of FBG and HbA1c. PMID- 27003662 TI - Erratum. PMID- 27003661 TI - [Research progress of Epstein-Barr virus-associated gastric carcinoma]. AB - Epstein-Barr virus-associated gastric carcinoma(EBVaGC) comprises nearly 10% of gastric carcinoma in the world. EBVaGC is supposed to have distinct clinicopathological features, including male predominance, the 'lace pattern' in the early stage, lower rate of lymph node involvement and infiltration of a large number of various inflammatory cells. EBER-ISH detection is the golden standard in the diagnosis of EBVaGC. Although there is no special therapy due to the limited understanding, EBVaGC has a better prognosis. In this paper, the relationship of EBV with gastric carcinoma, the epidemiological and clinical features of EBVaGC will be briefly introduced. In addition, the clinical diagnosis, treatment, and the prognosis of the status quo will be discussed. PMID- 27003664 TI - Benton Judgment of Line Orientation (JoLO) Test: A Brief and Useful Measure for Assessing Visuospatial Abilities in Manifest, but not Premanifest, Huntington's Disease. AB - BACKGROUND: Visuospatial deficits have been described in Huntington's disease (HD); however, the extent of these deficits remains unclear. The Benton Judgment of Line Orientation (JoLO) Test, commonly used to assess visuospatial ability, requires minimal motor involvement. It has demonstrated sensitivity to visuospatial deficits in Parkinson's disease; however, few studies have examined performance on this test in HD. OBJECTIVE: The objective of the current study was to assess visuospatial ability in premanifest and manifest HD using the JoLO. METHODS: A global cognitive measure, the Mattis Dementia Rating Scale (DRS), was used to stratify manifest HD patients as mild (DRS >=129) vs. moderate-severe (DRS <=128). Fifty mild, 42 moderate-severe, and 30 premanifest HD subjects, as well as 35 matched controls, were administered the JoLO. HD Burden of Pathology (BOP) scores were used as a measure of disease severity. RESULTS: Results revealed that the total manifest HD sample (p < 0.001), in addition to the mild (p = 0.028), and moderate-severe (p < 0.001), but not premanifest, HD subjects scored significantly lower on the JoLO compared to normal controls. CONCLUSIONS: Our results suggest that the JoLO is useful for detecting visuospatial deficits across various stages of manifest HD. However, any visuospatial impairment that might be present during the premanifest stage of HD was not detected using the JoLO in the present sample. PMID- 27003667 TI - GroE chaperonins assisted functional expression of bacterial enzymes in Saccharomyces cerevisiae. AB - Rapid advances in the capabilities of reading and writing DNA along with increasing understanding of microbial metabolism at the systems-level have paved an incredible path for metabolic engineering. Despite these advances, post translational tools facilitating functional expression of heterologous enzymes in model hosts have not been developed well. Some bacterial enzymes, such as Escherichia coli xylose isomerase (XI) and arabinose isomerase (AI) which are essential for utilizing cellulosic sugars, cannot be functionally expressed in Saccharomyces cerevisiae. We hypothesized and demonstrated that the mismatching of the HSP60 chaperone systems between bacterial and eukaryotic cells might be the reason these bacterial enzymes cannot be functionally expressed in yeast. The results showed that the co-expression of E. coli GroE can facilitate the functional expression of E. coli XI and AI, as well as the Agrobacterium tumefaciens D-psicose epimerase in S. cerevisiae. The co-expression of bacterial chaperonins in S. cerevisiae is a promising post-translational strategy for the functional expression of bacterial enzymes in yeast. Biotechnol. Bioeng. 2016;113: 2149-2155. (c) 2016 Wiley Periodicals, Inc. PMID- 27003666 TI - New Therapeutic Paradigms and Guidelines in the Management of Pulmonary Arterial Hypertension. AB - BACKGROUND: Recent and ongoing developments in the diagnosis, treatment, and management of pulmonary arterial hypertension (PAH) provide deeper insights into pathogenic mechanisms. Approvals of new pharmacotherapies that improve function and reduce morbidity and mortality risks; advances in clinical trial methods, including long-term, event-driven studies with clinically relevant and patient centered endpoints; and trial results support a new therapeutic management strategy. This new paradigm involves initial treatment with combined therapies that act through different disease pathways. In addition, 2 new sets of clinical practice guidelines for PAH have been published since June 2014. Despite these advances, major gaps have been documented in the diagnosis, treatment, and management of patients with PAH. OBJECTIVE: To present current knowledge and evidence on PAH to support managed care professionals and providers in achieving accurate differential diagnosis, promptly referring patients to specialists as necessary, and ensuring that patients receive appropriate, guideline-directed therapies. SUMMARY: Major gaps in the quality of care provided to patients with PAH include oversights in clinicians' recognition of symptoms, delays in diagnosis, and misdiagnosis ensuing from incomplete evaluations, delays in referral of patients to centers of expertise and initiation of therapy, and inappropriate treatment regimens. To address deficiencies in PAH diagnosis, new practice guidelines emphasize the essential role of right heart catheterization in characterizing and confirming the disease, as well as referral to expert pulmonary hypertension centers to ensure appropriate evaluation and treatment. Updated disease and functional classifications of PAH, along with new research findings on prognostic factors and effects of comorbid conditions, offer key support for making effective therapy and management decisions for patients with PAH at different risk levels and stages of the disease. Since 2013, the U.S. Food and Drug Administration has approved new PAH therapies in the classes of endothelin receptor antagonists, guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists. As demonstrated through phase 3 clinical trials, these generally well-tolerated therapies delay disease progression, improve hemodynamic and functional status, and decrease numbers of hospitalizations. Moreover, 2 sets of recently published guidelines-developed by the American College of Chest Physicians and the European Society of Cardiology/European Respiratory Society-provide evidence-based and expert consensus recommendations for achieving PAH treatment goals. The most recent guidelines include a recommendation for upfront combination therapy for patients with moderate disease, which is supported by new comparative clinical trial evidence. As addressed in this article, these advances in the field of PAH have important implications for managed care and clinical practice, including considerations of cost-benefit outcomes associated with different management strategies. PMID- 27003668 TI - The challenge and impact of engaging hard-to-reach populations in regular physical activity and health behaviours: an examination of an English Premier League 'Football in the Community' men's health programme. AB - OBJECTIVES: To investigate the challenges that men from hard-to-reach (HTR) populations encounter when attempting to commit to regular participation in physical activity and health behaviours, and to explore the psychological and social effects of participation in a twelve week football-led health improvement intervention. STUDY DESIGN: A twelve week football specific physical activity intervention targeting men from HTR populations was delivered by Everton Football Clubs' Football in the Community (FitC) scheme as part of a national programme of men's health delivered in/by English Premier League (EPL) football clubs. Men living in homeless shelters and/or recovering from substance misuse were recruited over a period of three months. The programme consisted of a two hour football session, twice weekly, alongside the dissemination of healthy living messages. Football sessions were conducted by a qualified FitC coach. METHODS: This research was conducted during a twelve week period of immersed practitioner research. Ethnographic and observational methodologies were adopted. Psychosocial issues were discussed with participants through informal client-researcher interactions and data were logged via field notes. Records of attendance were logged. Participants who failed to attend a session were contacted and their reason(s) for non-attendance were recorded. Data were analysed using deductive and inductive reasoning. RESULTS: Despite the apparent ambition of the participants to regularly participate in the FitC programme, adherence to the programme was poor. Economic, environmental and social barriers to engagement in the programme were apparent. Engagement in the programme resulted in positive psychosocial developments; the development of structure, social interaction and social capital. CONCLUSION: Community based football-led health improvement programmes endorsed by professional football clubs appear well positioned to connect with, and attract, men from HTR populations. The evidence suggests that such programmes can improve psychosocial health amongst these populations. However, a bottom-up programme design and management strategy is required in order to reduce the challenges facing HTR participants when attempting to regularly engage in physical activity and health behaviours. PMID- 27003670 TI - Hookah smoking behavior initiation in the context of Millennials. AB - OBJECTIVES: This study aims to examine current hookah users' perceptions, attitudes, and normative beliefs regarding hookah smoking to further elucidate the rise in hookah smoking prevalence among young adults (aged 18-24 years) and reveal why hookah smoking is perceived as less harmful than other forms of tobacco consumption. STUDY DESIGN: Qualitative. METHODS: Data from six focus group interviews with hookah smokers aged between 18 and 24 years were analyzed using a grounded theory approach. Focus groups were evenly split between frequent and infrequent hookah users, and were predominantly composed of college students, with two groups of hookah users consisting of 18-24 year olds of non-student status. RESULTS: Hookah users shared a much larger set of positive hookah smoking behavioral beliefs as opposed to negative behavioral beliefs. Generational traits served as the overarching commonality among the behavior performance initiation determinants observed. The most notable generational trends observed were within the cultural category, which included the following millennial characteristics: autonomy, personalization, novelty appeal, convenience, globally oriented, entertainment, collaboration, health conscious, and valuing their social network. CONCLUSIONS: Millennial hookah users revealed mindfulness regarding both potential negative and positive reasons stemming from continued hookah use; however, behavioral beliefs were primarily fixated on the perception that hookah smoking was a healthier alternative to cigarette smoking. Future implications for this study's findings include generating more positive ways to express these traits for young adults; policy implications include raising hookah bar age limits, implementing indoor smoking restrictions, and limiting the ease of accessibility for purchasing hookah supplies. PMID- 27003673 TI - Psychosocial characteristics and smoking behaviour in young Western Australian pregnant women at their first hospital appointment for pregnancy care. PMID- 27003660 TI - [Research advance in causes of postoperative gastrointestinal dysfunction]. AB - Gastrointestinal dysfunction is a common and major complication after surgery. The syndrome covers a wide spectrum of clinical signs, ranges from mild feeling to severe discomfort and varies from person to person. The mild patients need no care, but severe ones may have long hospital stay, and even suffer from multiple organ dysfunction syndrome, severely affecting postoperative rehabilitation. However, the etiology of postoperative gastrointestinal dysfunction has not been fully elucidated. Much research demonstrates that many factors, such as operative procedures, surgical operation, homeostasis disturbance, anesthesia and analgesia, blood perfusion, inflammation, and neuroendocrine factors, are responsible for the development and progression of postoperative gastrointestinal dysfunction. This study therefore reviewed the causes of postoperative gastrointestinal dysfunction in the published literatures. PMID- 27003674 TI - Does the food retail environment reflect UK public health recommendations for healthy eating? PMID- 27003669 TI - Physical activity, but not dietary intake, attenuates the effect of the FTO rs9939609 polymorphism on obesity and metabolic syndrome in Lithuanian adult population. AB - OBJECTIVES: This study aimed to examine the associations between the fat mass and obesity associated (FTO) gene rs9939609 variant with obesity and metabolic syndrome and interactions between FTO alleles, dietary intake and physical activity in Lithuanian adult population. STUDY DESIGN: Cross-sectional study. METHODS: A health survey was carried out in randomly selected municipalities of Lithuania. The random sample was obtained from the lists of 25-64 year-old inhabitants. The data from 1020 individuals were analyzed. The single-nucleotide polymorphism, rs9939609, in the FTO gene was assessed using a real-time polymerase chain reaction. 24-hour recall was used for evaluation of dietary habits. Information on physical activity at work, traveling to and from work and at leisure time was gathered by a standard questionnaire. RESULTS: The carriers of the AA genotype had the highest mean values of body mass index (BMI) and waist circumference (WC). They had 1.72 time higher odds of obesity (P = 0.009) and 1.67 time higher odds of increased WC (P = 0.013) than those with the TT genotype. Carriers of the T allele had lower prevalence of metabolic syndrome compared to carriers of the AA genotype (33.8% and 42.5% respectively; P = 0.018). No interaction between the rs9939609 variant and energy or dietary intakes on weight status was found. Significant effect of the interactions 'genotype*age' and 'genotype*physical activity' on BMI was demonstrated. The FTO rs9939609 polymorphism was associated with anthropometric parameters and metabolic syndrome in the younger age group (25-44 years) and in individuals having low level of physical activity. CONCLUSIONS: Age and physical activity modulated the effect of the FTO polymorphism on weight status and metabolic syndrome in Lithuanian adult population. PMID- 27003671 TI - Birth outcomes in a tertiary teaching hospitals and local outposts: a novel approach to service delivery from Iran. AB - OBJECTIVE: The aim of this study was to compare the outcomes of childbirth care in a tertiary teaching hospital and Safe Delivery Posts (SDPs) to determine the safety of out-of-hospital care by midwives in Zahedan, Iran. STUDY DESIGN: A quasi-experimental design was applied in this study. METHODS: In this study, 2063 women who gave birth in SDPs, along with 983 women who underwent vaginal delivery in a tertiary teaching hospital, were evaluated in 2011-2012. Retrospective chart review was applied to collect data from the medical records of mothers and neonates. Only low-risk women with a singleton live birth, cephalic presentation, gestational age >=37 weeks, spontaneous labour, and no prior history of uterine scar were recruited. RESULTS: Based on the findings, episiotomy, perineal tear, cervical laceration, postpartum haemorrhage and need for blood transfusion (or hysterectomy) were less commonly reported in the SDP group, compared to the hospital group. In the SDP group, 15 (0.73%) women were transferred to the hospital after delivery. Overall, one (0.10%) case from the hospital group and two (0.10%) cases from the SDP group were admitted to the intensive care unit. One-minute Apgar score lower than seven, resuscitation, NICU admission and neonatal death were more commonly reported in the hospital group, compared to the SDP group. Overall, hospital transfer was reported in 12 (0.58%) neonates born in SDPs. CONCLUSION: In the present study, women who gave birth in SDPs had more opportunities to experience natural birth with fewer adverse outcomes. However, considering the possibility of life-threatening complications for mothers and newborns, substantial evidence is required to improve the quality of care before implementing such novel strategies in different settings. PMID- 27003672 TI - Validity of self-reported versus actual age in Nepali children and young people. PMID- 27003675 TI - Immunoglobulin isotype knowledge and application to Fc engineering. AB - Monoclonal antibody-based drugs continue to be one of the most rapidly growing classes of therapeutic molecules. At present, the majority of approved therapeutic antibodies are of the human IgG1 format, which can elicit immune effector functions (e.g., antibody-dependent cellular cytotoxicity, antibody dependent cellular phagocytosis, and complement-dependent cytotoxicity). However, there is a wealth of functional diversity that is present in other isotypes and IgG subclasses that can be exploited to improve clinical safety and performance by increasing stability, reduction of adverse events, modulation of effector functions, and by the engagement of two antigens by a single antibody. This review presents an overview of the different antibody isotypes and subclasses and details how exchanging amino acids between different isotypes (i.e., 'cross isotypes') can be exploited to generate novel therapeutic platforms. PMID- 27003663 TI - Participants at the Leiden Site of the REGISTRY Study: A Demographic Approach. AB - BACKGROUND: REGISTRY is the largest European observational study of Huntington's disease (HD). The Leiden University Medical Center (LUMC) in The Netherlands is the largest recruiting site. OBJECTIVE: The aim of this paper is to give an overview of the baseline characteristics of all Leiden participants from the start of the study in 2005 until the close of REGISTRY at the LUMC in September 2014. METHODS: The Leiden cohort is described in two different ways: CAG repeat length and presence of motor signs. RESULTS: Division into groups based on prolonged CAG length revealed that the cohort consists of 4 intermediate - (27-35 CAG), 22 reduced penetrance - (36-39 CAG), 465 full penetrance - (>39 CAG) and 60 control participants (<27 CAG). The second way of dividing the participants based on present or absent of motor signs, showed that 170 pre-motormanifest - and 317 motormanifest participants were enrolled. CONCLUSION: The Leiden REGISTRY cohort at baseline is mainly characterized by full penetrance gene expansion carriers who have been clinically diagnosed with HD but who remain relatively functionally independent. For the majority of these participants, disease onset was based on motor signs followed by psychiatric and cognitive signs. PMID- 27003665 TI - Does the Mutant CAG Expansion in Huntingtin mRNA Interfere with Exonucleolytic Cleavage of its First Exon? AB - BACKGROUND: Silencing mutant huntingtin mRNA by RNA interference (RNAi) is a therapeutic strategy for Huntington's disease. RNAi induces specific endonucleolytic cleavage of the target HTT mRNA, followed by exonucleolytic processing of the cleaved mRNA fragments. OBJECTIVES: We investigated the clearance of huntingtin mRNA cleavage products following RNAi, to find if particular huntingtin mRNA sequences persist. We especially wanted to find out if the expanded CAG increased production of a toxic mRNA species by impeding degradation of human mutant huntingtin exon 1 mRNA. METHODS: Mice expressing the human mutant HTT transgene with 128 CAG repeats (YAC128 mice) were injected in the striatum with self-complementary AAV9 vectors carrying a miRNA targeting exon 48 of huntingtin mRNA (scAAV-U6-miRNA-HTT-GFP). Transgenic huntingtin mRNA levels were measured in striatal lysates after two weeks. For qPCR, we used species specific primer-probe combinations that together spanned 6 positions along the open reading frame and untranslated regions of the human huntingtin mRNA. Knockdown was also measured in the liver following tail vein injection. RESULTS: Two weeks after intrastriatal administration of scAAV9-U6-miRNA-HTT-GFP, we measured transgenic mutant huntingtin in striatum using probes targeting six different sites along the huntingtin mRNA. Real time PCR showed a reduction of 29% to 36% in human HTT. There was no significant difference in knockdown measured at any of the six sites, including exon 1. In liver, we observed a more pronounced HTT mRNA knockdown of 70% to 76% relative to the untreated mice, and there were also no significant differences among sites. CONCLUSIONS: Our results demonstrate that degradation is equally distributed across the human mutant huntingtin mRNA following RNAi-induced cleavage. PMID- 27003677 TI - Improving the quantitative accuracy of cerebral oxygen saturation in monitoring the injured brain using atlas based Near Infrared Spectroscopy models. AB - The application of Near Infrared Spectroscopy (NIRS) for the monitoring of the cerebral oxygen saturation within the brain is well established, albeit using temporal data that can only measure relative changes of oxygenation state of the brain from a baseline. The focus of this investigation is to demonstrate that hybridisation of existing near infrared probe designs and reconstruction techniques can pave the way to produce a system and methods that can be used to monitor the absolute oxygen saturation in the injured brain. Using registered Atlas models in simulation, a novel method is outlined by which the quantitative accuracy and practicality of NIRS for specific use in monitoring the injured brain, can be improved, with cerebral saturation being recovered to within 10.1 +/- 1.8% of the expected values. PMID- 27003680 TI - Adrenal Molecular Imaging. AB - The major workload in the field of adrenal imaging comprises patients with adrenal tumors incidentally depicted by imaging performed for other reasons than adrenal disease. These so-called 'incidentalomas' are generally managed by CT and MRI, and molecular imaging techniques are required only for a few patients. PET/CT with 18F-fluorodeoxyglucose (18F-FDG) is useful for establishing whether an adrenal metastasis is the only lesion, and therefore is available for surgical resection, or if the disease is disseminated. 18F-FDG PET/CT may be applied to differ benign from malignant incidentalomas and can be helpful in the imaging of pheochromocytoma and adrenocortical cancer (ACC). 11C-metomidate PET/CT can differentiate adrenocortical from nonadrenocortical tumors and a suspected ACC may be characterized and staged before surgery. 11C-metomidate PET/CT is currently also used to help diagnose Conn's adenomas in primary aldosteronism, but further development is needed. Scintigraphy with 123I/131I metaiodobenzylguanidine (MIBG) remains the mainstay for molecular imaging of pheochromocytoma and is mandatory in patients for whom 131I-MIBG therapy is considered. A PET tracer for the imaging of pheochromocytoma is the norepinephrine analogue (11)C-hydroxyephedrine that can be used to characterize equivocal lesions and for the follow-up and diagnosis of recurrent malignant disease. Other specialized PET tracers for the imaging of pheochromocytoma are 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-fluorodopamine. PMID- 27003676 TI - Effects of the Reread-Adapt and Answer-Comprehend and goal setting intervention on decoding and reading comprehension skills of young adults with intellectual disabilities. AB - OBJECTIVE: Reread-Adapt and Answer-Comprehend (RAAC) + Goal Setting intervention is a reading intervention that addresses both oral reading fluency (ORF) and reading comprehension while supporting persistence and motivation for learners who struggle with reading. METHOD: We delivered the RAAC + Goal Setting intervention to five young adult learners with intellectual disabilities (ID) in a postsecondary education setting. In the study, we investigated the effects of the intervention on generalization of reading skills to novel passages. RESULTS: Utilizing a response-guided and randomized multiple-baseline across the participants' design, we failed to reject the null hypothesis of no treatment effects based on the computed p-value. Traditional visual analysis of the data also reached a similar conclusion, however, we found that two participants' decoding skills improved during the intervention. CONCLUSIONS: We did not find a functional relation between the intervention and student reading performance. PMID- 27003681 TI - Prolonged Duration of Renal Recovery Following ANCA-Associated Glomerulonephritis. AB - BACKGROUND: As renal biopsies are not routinely repeated to monitor treatment response in anti-neutrophil cytoplasm antibody (ANCA)-associated glomerulonephritis, serum creatinine (SC) and proteinuria assessed by urine protein:creatinine ratio (UPCR) measurements are relied upon to provide a non invasive estimate of disease activity within the kidney. However, sparse information exists about the time to achieve maximal improvement in these parameters, which has important implications for treatment decisions and disease scoring systems. METHODS: We analysed patients with ANCA-associated glomerulonephritis and renal impairment from cohorts in the United Kingdom and Ireland, with the primary objective of determining actuarial time to nadir SC and UPCR. Time to disappearance of haematuria was analysed as a secondary objective. RESULTS: Ninety-four patients fulfilled our selection criteria, with 94 (100%) and 66 (70%) having reached their nadir SC and UPCR respectively during the follow-up period. Nadir SC was achieved after a median of 88 days (95% CI 74 102), UPCR at 346 days (95% CI 205-487). Those of Indo-Asian ethnic origin reached their nadir SC faster (34 days) than other ethnicities (p < 0.01). There were no significant differences in time to nadir SC or UPCR on the basis of gender, clinical diagnosis, ANCA positivity or renal biopsy findings. CONCLUSION: In this retrospective study, nadir creatinine and proteinuria occur later than other signs of clinical remission, suggesting that ongoing renal recovery continues for a significant time after diagnosis. It may benefit disease-scoring systems to take into account SC levels beyond the initial assessment. PMID- 27003679 TI - Norovirus diarrhea in Bangladesh, 2010-2014: prevalence, clinical features, and genotypes. AB - Norovirus infections in diarrhea patients attending an urban and a rural hospital in Bangladesh were investigated. A total of 953 fecal specimens from both children and adults collected during 2010-2014 were tested for the presence of norovirus using real time PCR. One fourth (25%) of the specimens were positive for norovirus RNA which was identified both in children and adults. Norovirus was associated with short duration of diarrhea, high abdominal pain, and more moderate to severe dehydration when compared with rotavirus infections. Norovirus GII (69%) was the most prevalent genogroup followed by GI (18%), mixed GI/GII/GIV (11%), and GIV (2%). Among GII genogroup, GII.4 (42%) was the most prevalent genotype followed by GII.3 (21%), GII.6 (7%), GII.7 (6%), and GII.21 (6%). GII.4 and GII.3 strains were frequently identified (82% and 75%, respectively) in children <2 years of age and less commonly (16% and 15%) in adults more than 18 years of age. The present study reinforces the importance of norovirus-associated hospitalizations both in children and adults. The dynamic molecular epidemiology of norovirus requires routine strain surveillance to identify changes in prevailing strains. J. Med. Virol. 88:1742-1750, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27003678 TI - Fighting Oxidative Stress: Increased Resistance of Male Rat Cerebellum at Weaning Induced by Low Omega 6/Omega 3 Ratio in a Protein-Deficient Diet. AB - The cerebellum is vulnerable to malnutrition effects. Notwithstanding, it is able to incorporate higher amount of docosahexaenoic acid (DHA) than the cerebral cortex (Cx) when low n-6/n-3 fatty acid ratio is present in a multideficient diet. Considering importance of DHA for brain redox balance, we hypothesize that this cerebellum feature improves its antioxidant status compared to the Cx. A chronic malnutrition status was induced on dams before mating and kept until weaning or adulthood (offspring). A group nutritionally rehabilitated from weaning was also analyzed. Morphometric parameters, total-superoxide dismutase (t SOD) and catalase activities, lipoperoxidation (LP), nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, reactive oxygen species (ROS), and reduced nicotinamide adenine dinucleotide/phosphate levels were assessed. Both ROS and LP levels were increased (~53 %) in the Cx of malnourished young animals while the opposite was seen in the cerebellum (72 and 20 % of the control, respectively). Consistently, lower (~35 %) and higher t-SOD (~153 %) and catalase (CAT) (~38 %) activities were respectively detected in the Cx and cerebellum compared to the control. In malnourished adult animals, redox balance was maintained in the cerebellum and recovered in the Cx (lower ROS and LP levels and higher GSH/GSSG ratio). NO production was impaired by malnutrition at either age, mainly in the cerebellum. The findings suggest that despite a multinutrient deficiency and a modified structural development, a low dietary n-6/n-3 ratio favors early antioxidant resources in the male cerebellum and indicates an important role of astrocytes in the redox balance recovery of Cx in adulthood. PMID- 27003685 TI - Dual Role (Anti- and Pro-oxidant) of Gallic Acid in Mediating Myofibrillar Protein Gelation and Gel in Vitro Digestion. AB - The dose-dependent effects of gallic acid (GA; at 0, 6, 30, and 150 MUmol/g protein) on chemical changes and gelling properties of oxidatively stressed porcine myofibrillar protein (MP) and in vitro digestibility of the gels were investigated. The incorporation of GA suppressed lipid oxidation and protein carbonyl formation but promoted the loss of thiol and amine groups, destabilization of the tertiary structure, aggregation, and cross-linking. The gelling potential (storage modulus) of MP was increased by nearly 50% with 6 and 30 MUmol/g of GA, corresponding to enhanced protein unfolding and aggregation and formation of disulfide-dominant covalent bonds. However, GA at 150 MUmol/g induced macroscopic aggregations and insolubility of MP, resulting in poorly structured gels. Despite the oxidative changes, MP gels did not show reduced susceptibility to digestive enzymes in vitro. PMID- 27003683 TI - Extreme obesity induces massive beta cell expansion in mice through self-renewal and does not alter the beta cell lineage. AB - AIMS/HYPOTHESIS: Understanding the developmental biology of beta cell regeneration is critical for developing new diabetes therapies. Obesity is a potent but poorly understood stimulus for beta cell expansion. Current models of obesity are complicated by developmental compensation or concurrent diabetes, limiting their usefulness for identifying the lineage mechanism(s) of beta cell expansion. We aimed to determine whether acute inducible obesity stimulates beta cell expansion and to determine the lineage mechanism of beta cell growth in obesity. METHODS: We created whole-body tamoxifen-inducible leptin receptor (LepR)-deficient mice (Ubc-Cre (ERT2) LepR (loxP/loxP) ) as a novel model of acute obesity. Beta cell mass and proliferation were quantified after short-term LepR deletion. Clonal analysis of beta cell expansion using the Brainbow2.1 reporter was performed 6 months post tamoxifen initiation. RESULTS: LepR deficiency induced a doubling of body mass within 3 weeks, with moderate glucose intolerance (unlike typical LepR mutant mice [db/db], which have frank diabetes). Beta cell mass expanded threefold through increased beta cell proliferation, without evidence for contribution from specialised progenitors or stem cells (via sequential thymidine labelling and Brainbow2.1 reporter). Thus, self-renewal is the primary lineage mechanism in obesity-induced beta cell expansion. However, even the rapid beta cell proliferation could not exceed the restrictions of the replication refractory period. CONCLUSIONS/INTERPRETATION: In summary, we created a novel model of inducible obesity demonstrating that even extreme metabolic demand does not alter beta cell lineage. PMID- 27003686 TI - Non-hermitian quantum thermodynamics. AB - Thermodynamics is the phenomenological theory of heat and work. Here we analyze to what extent quantum thermodynamic relations are immune to the underlying mathematical formulation of quantum mechanics. As a main result, we show that the Jarzynski equality holds true for all non-hermitian quantum systems with real spectrum. This equality expresses the second law of thermodynamics for isothermal processes arbitrarily far from equilibrium. In the quasistatic limit however, the second law leads to the Carnot bound which is fulfilled even if some eigenenergies are complex provided they appear in conjugate pairs. Furthermore, we propose two setups to test our predictions, namely with strongly interacting excitons and photons in a semiconductor microcavity and in the non-hermitian tight-binding model. PMID- 27003684 TI - A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice. AB - AIM/HYPOTHESIS: MicroRNA-9 (miR-9) is involved in the regulation of pancreatic beta cell function. However, its role in gluconeogenesis is still unclear. Our objective was to investigate the role of miR-9 in hepatic glucose production (HGP). METHODS: MiR-9 expression was measured in livers of high-fat diet (HFD) mice and ob/ob mice. The methylation status of the miR-9-3 promoter regions in hepatocytes was determined by the methylation-specific PCR procedure. The binding activity of DNA methyltransferase (DNMT)1, DNMT3a and DNMT3b on the miR-9-3 promoter was detected by chromatin immunoprecipitation (ChIP) and quantitative real-time PCR assays. HGP was evaluated in vitro and in vivo. Glucose tolerance, insulin tolerance and pyruvate tolerance tests were also performed. RESULTS: Reduced miR-9 expression and hypermethylation of the miR-9-3 promoter were observed in the livers of obese mice. Further study showed that the binding of DNMT1, but not of DNMT3a and DNMT3b, to the miR-9-3 promoter was increased in hepatocytes from ob/ob mice. Knockdown of DNMT1 alleviated the decrease in hepatic miR-9 expression in vivo and in vitro. Overexpression of hepatic miR-9 improved insulin sensitivity in obese mice and inhibited HGP. In addition, deletion of hepatic miR-9 led to an increase in random and fasting blood glucose levels in lean mice. Importantly, silenced forkhead box O1 (FOXO1) expression reversed the gluconeogenesis and glucose production in hepatocytes induced by miR 9 deletion. CONCLUSIONS/INTERPRETATION: Our observations suggest that the decrease in miR-9 expression contributes to an inappropriately activated gluconeogenesis in obese mice. PMID- 27003692 TI - Tunable Lattice Constant and Band Gap of Single- and Few-Layer ZnO. AB - Single and few-layer ZnO(0001) (ZnO(nL), n = 1-4) grown on Au(111) have been characterized via scanning tunneling microscopy (STM), scanning tunneling spectroscopy (STS), and density functional theory (DFT) calculations. We find that the in-plane lattice constants of the ZnO(nL, n <= 3) are expanded compared to that of the bulk wurtzite ZnO(0001). The lattice constant reaches a maximum expansion of 3% in the ZnO(2L) and decreases to the bulk wurtzite ZnO value in the ZnO(4L). The band gap decreases monotonically with increasing number of ZnO layers from 4.48 eV (ZnO(1L)) to 3.42 eV (ZnO(4L)). These results suggest that a transition from a planar to the bulk-like ZnO structure occurs around the thickness of ZnO(4L). The work also demonstrates that the lattice constant and the band gap in ultrathin ZnO can be tuned by controlling the number of layers, providing a basis for further investigation of this material. PMID- 27003688 TI - Visceral Obesity Mediates the Association Between Metabolic Syndrome and Obstructive Sleep Apnea Syndrome. AB - BACKGROUND: Metabolic syndrome (MetS) and visceral obesity are more prevalent in obstructive sleep apnea syndrome (OSAS). We investigated the association of visceral fat (VF) measures with the components of MetS in OSAS patients with different severity levels, according to World Health Organization (WHO, 1999), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III, 2001), and International Diabetes Federation (IDF, 2005) definitions. PATIENTS AND METHODS: Study population was grouped according to polysomnography results as non-OSAS [who had apnea-hypopnea index (AHI) <5, n = 51], mild OSAS (5 < AHI <15, n = 52), moderate OSAS (15 < AHI <30, n = 53), and severe OSAS (AHI >30, n = 53). VF ratio was measured by abdominal bioimpedance analysis. Waist-to-hip ratio (WHR), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were assessed in all subjects. RESULTS: The prevelance of MetS in OSAS patients was 30.0%, 35.6%, and 44.4% according to WHO, NCEP-ATP III, and IDF definitions, respectively. MetS was found in 27.5% non-OSAS and 72.8% OSAS according to at least one definition (P = 0.012). Within OSAS group, 27.2% subjects had average, 38.0% had slightly excessive, and 34.8% had an excessive VF ratio. The prevelance of MetS was similar in various VF ratios (P > 0.05). However HOMA-IR increased progressively with VF ratio after adjusting for age, gender, and body mass index (BMI; P = 0.02). AHI increased progressively with BMI (P = 0.02), WHR (P = 0.03), VF ratio (P = 0.01), HOMA-IR (P = 0.02), and MetS (P = 0.016). CONCLUSION: Since severity of OSAS, in terms of AHI and insulin resistance, is both associated with VF rather than BMI, VF should be suggested to link OSAS and MetS. The IDF definition is more sensitive in OSAS patients to diagnose MetS, as central obesity and insulin resistance are obligatory components. This would allow clinicians to intervent earlier to adverse metabolic outcomes of OSAS. PMID- 27003682 TI - Noise Expands the Response Range of the Bacillus subtilis Competence Circuit. AB - Gene regulatory circuits must contend with intrinsic noise that arises due to finite numbers of proteins. While some circuits act to reduce this noise, others appear to exploit it. A striking example is the competence circuit in Bacillus subtilis, which exhibits much larger noise in the duration of its competence events than a synthetically constructed analog that performs the same function. Here, using stochastic modeling and fluorescence microscopy, we show that this larger noise allows cells to exit terminal phenotypic states, which expands the range of stress levels to which cells are responsive and leads to phenotypic heterogeneity at the population level. This is an important example of how noise confers a functional benefit in a genetic decision-making circuit. PMID- 27003687 TI - Population-Scale Foraging Segregation in an Apex Predator of the North Atlantic. AB - In this work we investigated the between-colony spatial, behavioural and trophic segregation of two sub-populations of the elusive Macaronesian shearwaters Puffinus baroli breeding only ~340 km apart in Cima Islet (Porto Santo Island) and Selvagem Grande Island. Global location sensing (gls) loggers were used in combination with the trophic ecology of tracked individuals, inferred from the isotopic signatures of wing feathers. Results suggest that these two Macaronesian shearwater sub-populations do segregate during the non-breeding period in some 'sub-population-specific' regions, by responding to different oceanographic characteristics (habitat modelling). Within these disparate areas, both sub populations behave differently (at-sea activity) and prey on disparate trophic niches (stable isotope analysis). One hypothesis would be that each sub population have evolved and adapted to feed on particular and 'sub-population specific' resources, and the segregation observed at the three different levels (spatial, behavioural and trophic) might be in fact a result of such adaptation, from the emergence of 'cultural foraging patterns'. Finally, when comparing to the results of former studies reporting on the spatial, behavioural and trophic choices of Macaronesian shearwater populations breeding on Azores and Canary Islands, we realized the high ecological plasticity of this species inhabiting and foraging over the North-East Atlantic Ocean. PMID- 27003689 TI - Integrating subsistence practice and species distribution modeling: assessing invasive elodea's potential impact on Native Alaskan subsistence of Chinook salmon and whitefish. AB - Alaska has one of the most rapidly changing climates on earth and is experiencing an accelerated rate of human disturbance, including resource extraction and transportation infrastructure development. Combined, these factors increase the state's vulnerability to biological invasion, which can have acute negative impacts on ecological integrity and subsistence practices. Of growing concern is the spread of Alaska's first documented freshwater aquatic invasive plant Elodea spp. (elodea). In this study, we modeled the suitable habitat of elodea using global and state-specific species occurrence records and environmental variables, in concert with an ensemble of model algorithms. Furthermore, we sought to incorporate local subsistence concerns by using Native Alaskan knowledge and available statewide subsistence harvest data to assess the potential threat posed by elodea to Chinook salmon (Oncorhynchus tshawytscha) and whitefish (Coregonus nelsonii) subsistence. State models were applied to future climate (2040-2059) using five general circulation models best suited for Alaska. Model evaluations indicated that our results had moderate to strong predictability, with area under the receiver-operating characteristic curve values above 0.80 and classification accuracies ranging from 66 to 89 %. State models provided a more robust assessment of elodea habitat suitability. These ensembles revealed different levels of management concern statewide, based on the interaction of fish subsistence patterns, known spawning and rearing sites, and elodea habitat suitability, thus highlighting regions with additional need for targeted monitoring. Our results suggest that this approach can hold great utility for invasion risk assessments and better facilitate the inclusion of local stakeholder concerns in conservation planning and management. PMID- 27003691 TI - Certification of competitive sports participation of a professional soccer player with hypertrophic cardiomyopathy and implanted ICD. PMID- 27003698 TI - Examining dog-human play: the characteristics, affect, and vocalizations of a unique interspecific interaction. AB - Despite the growing interest in research on the interaction between humans and dogs, only a very few research projects focus on the routines between dogs and their owners. In this study, we investigated one such routine: dog-human play. Dyadic interspecific play is known to be a common interaction between owner and charge, but the details of what counts as play have not been thoroughly researched. Similarly, though people represent that "play" is pleasurable, no study has yet undertaken to determine whether different forms of play are associated with different affective states. Thus, we aimed to generate an inventory of the forms of dyadic play, the vocalizations within play, and to investigate the relationship of affect to elements of play. Via a global citizen science project, we solicited videotapes of dog-human play sessions from dog owners. We coded 187 play bouts via frame-by-frame video playback. We then assessed the relationship between various intra-bout variables and owner affect (positive or neutral) during play (dog affect was overwhelmingly positive). Amount of physical contact ("touch"), level of activity of owner ("movement"), and physical closeness of dog-owner dyad ("proximity") were highly correlated with positive affect. Owner vocalizations were found to contain different elements in positive- and neutral-affect play. One novel category of play, "tease", was found. We conclude that not all play is created equal: the experience of play to the owner participant is strongly related to a few identifiable characteristics of the interaction. PMID- 27003690 TI - Prevalence of thrombophilic disorders in takotsubo patients: the (ThROmbophylia in TAkotsubo cardiomyopathy) TROTA study. AB - Takotsubo cardiomyopathy (TTC) pathophysiology is still unclear. A transient intracoronary thrombosis dissolved at the time of angiography has been hypothesized. We aimed to evaluate the prevalence of thrombophilic disorders in TTC patients. In 75 TTC women, 75 age- and sex-matched acute coronary syndrome (ACS) patients, both enrolled during the acute phase, and in 75 control subjects, we compared the prevalence of congenital and acquired thrombophilic alterations and the values of clotting and endothelial activation biomarkers. Some parameters were re-assessed 1 month after the acute phase in TTC patients. No significant difference between the three groups was observed in factor II (G20210A) and V (G1691A) polymorphisms prevalence. Homocysteine levels were significantly higher in ACS patients vs. TTC and control subjects. Lipoprotein(a) values trended to be higher in TTC patients vs. control subjects, though not significantly. Other thrombophilic alterations in TTC patients were similar to that previously reported in healthy women. Von Willebrand factor and plasminogen activator inhibitor-1 were significantly higher in TTC and in ACS patients than controls. Clotting activation biomarkers were not statistically different between TTC patients and controls. During follow-up, in TTC patients, endothelial damage indices significantly decreased while clotting activation biomarkers remained unchanged. In conclusion, our results, showing a rate of thrombophilic alterations in TTC patients similar to control subjects, do not support the transient intracoronary thrombus hypothesis. However, several endothelial damage markers and lipoprotein(a) were higher in TTC patients vs. controls suggesting a role of endothelial dysfunction and of other factors concurring to hyperviscosity, as recently hypothesized. PMID- 27003697 TI - Sulfide-oxidizing bacteria establishment in an innovative microaerobic reactor with an internal silicone membrane for sulfur recovery from wastewater. AB - A novel bioreactor, employing a silicone membrane for microaeration, was studied for partial sulfide oxidation to elemental sulfur. The objective of this study was to assess the feasibility of using an internal silicone membrane reactor (ISMR) to treat dissolved sulfide and to characterize its microbial community. The ISMR is an effective system to eliminate sulfide produced in anaerobic reactors. Sulfide removal efficiencies reached 96 % in a combined anaerobic/microaerobic reactor and significant sulfate production did not occur. The oxygen transfer was strongly influenced by air pressure and flow. Pyrosequencing analysis indicated various sulfide-oxidizing bacteria (SOB) affiliated to the species Acidithiobacillus thiooxidans, Sulfuricurvum kujiense and Pseudomonas stutzeri attached to the membrane and also indicated similarity between the biomass deposited on the membrane wall and the biomass drawn from the material support, supported the establishment of SOB in an anaerobic sludge under microaerobic conditions. Furthermore, these results showed that the reactor configuration can develop SOB under microaerobic conditions and can improve and reestablish the sulfide conversion to elemental sulfur. PMID- 27003694 TI - Tasimelteon: A Review in Non-24-Hour Sleep-Wake Disorder in Totally Blind Individuals. AB - Tasimelteon (Hetlioz((r))) is a dual melatonin receptor agonist indicated for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24) (free-running disorder). In two randomized, double-masked, multicentre, phase III trials, totally blind individuals with Non-24 who received oral tasimelteon 20 mg once nightly were significantly more likely than those receiving placebo to entrain the circadian pacemaker (the SET trial) and maintain entrainment (the RESET trial). Sleep/wake parameters and functioning were also improved with tasimelteon. Oral tasimelteon was generally well tolerated in totally blind patients with Non-24. In conclusion, tasimelteon is a useful drug for the treatment of Non-24 in totally blind individuals. PMID- 27003700 TI - Processes driving short-term temporal dynamics of small mammal distribution in human-disturbed environments. AB - As the impact of anthropogenic activities intensifies worldwide, an increasing proportion of landscape is converted to early successional stages every year. To understand and anticipate the global effects of the human footprint on wildlife, assessing short-term changes in animal populations in response to disturbance events is becoming increasingly important. We used isodar habitat selection theory to reveal the consequences of timber harvesting on the ecological processes that control the distribution dynamics of a small mammal, the red backed vole (Myodes gapperi). The abundance of voles was estimated in pairs of cut and uncut forest stands, prior to logging and up to 2 years afterwards. A week after logging, voles did not display any preference between cut and uncut stands, and a non-significant isodar indicated that their distribution was not driven by density-dependent habitat selection. One month after harvesting, however, juvenile abundance increased in cut stands, whereas the highest proportions of reproductive females were observed in uncut stands. This distribution pattern appears to result from interference competition, with juveniles moving into cuts where there was weaker competition with adults. In fact, the emergence of source-sink dynamics between uncut and cut stands, driven by interference competition, could explain why the abundance of red-backed voles became lower in cut (the sink) than uncut (the source) stands 1-2 years after logging. Our study demonstrates that the influences of density-dependent habitat selection and interference competition in shaping animal distribution can vary frequently, and for several months, following anthropogenic disturbance. PMID- 27003693 TI - Genetic control of nucleolar size: An evolutionary perspective. AB - Exploiting a C. elegans mutant (ncl-1) exhibiting nucleolar abnormalities, we recently identified the let-7/ncl-1/fib-1 genetic cascade underlying proper rRNA abundance and nucleolar size. These 3 factors, let-7 (a miRNA), NCL-1 (a member of the TRIM-NHL family), and fibrillarin (a nucleolar methyltransferase), are evolutionarily conserved across metazoans. In this article, we provide several lines of bioinformatic evidence showing that human and Drosophila homologues of C. elegans NCL-1, TRIM-71 and Brat, respectively, likely act as translational suppressors of fibrillarin. Moreover, since their 3'-UTRs contain putative target sites, they may also be under the control of the let-7 miRNA. We hypothesize that let-7, TRIM and fibrillarin contribute activities in concert, and constitute a conserved network controlling nucleolar size in eukaryotes. We provide an in depth literature review of various molecular pathways, including the let-7/ncl 1/fib-1 genetic cascade, implicated in the regulation of nucleolar size. PMID- 27003701 TI - Moss stable isotopes (carbon-13, oxygen-18) and testate amoebae reflect environmental inputs and microclimate along a latitudinal gradient on the Antarctic Peninsula. AB - The stable isotope compositions of moss tissue water (delta(2)H and delta(18)O) and cellulose (delta(13)C and delta(18)O), and testate amoebae populations were sampled from 61 contemporary surface samples along a 600-km latitudinal gradient of the Antarctic Peninsula (AP) to provide a spatial record of environmental change. The isotopic composition of moss tissue water represented an annually integrated precipitation signal with the expected isotopic depletion with increasing latitude. There was a weak, but significant, relationship between cellulose delta(18)O and latitude, with predicted source water inputs isotopically enriched compared to measured precipitation. Cellulose delta(13)C values were dependent on moss species and water content, and may reflect site exposure to strong winds. Testate amoebae assemblages were characterised by low concentrations and taxonomic diversity, with Corythion dubium and Microcorycia radiata types the most cosmopolitan taxa. The similarity between the intra- and inter-site ranges measured in all proxies suggests that microclimate and micro topographical conditions around the moss surface were important determinants of proxy values. Isotope and testate amoebae analyses have proven value as palaeoclimatic, temporal proxies of climate change, whereas this study demonstrates that variations in isotopic and amoeboid proxies between microsites can be beyond the bounds of the current spatial variability in AP climate. PMID- 27003699 TI - The Effect of Roux-en-Y vs. Omega-Loop Gastric Bypass on Liver, Metabolic Parameters, and Weight Loss. AB - BACKGROUND: Omega-loop gastric bypass (OLGB) results in weight loss (WL) but data on its impact on liver and glucose metabolism compared to Roux-en-Y gastric bypass (RYGB) is lacking. Therefore, the aim of this study was to compare the development of hepatic and metabolic markers as well as WL between the above mentioned surgical groups during the first postoperative year. METHODS: We retrospectively evaluated the respective parameters in non-diabetic morbidly obese patients who underwent either RYGB (n = 25) or OLGB (n = 25). RESULTS: Compared to RYGB, OLGB showed a greater WL percentage. Liver transaminases dropped in RYGB, while rose in OLGB. No correlation between aspartate transaminase, alanine transaminase, and WL could be detected. Gamma glutamyltransferase decreased significantly in RYGB over the first 3 months, while it increased in OLGB. We found higher levels of triglycerides, insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), and liver fat percentage in RYGB at baseline, despite matching the groups for age, sex, and BMI. Those differences disappeared, except for triglycerides, within 1 year. All metabolic parameters correlated with WL. CONCLUSION: OLGB results in greater WL but transiently deteriorated several liver parameters in the first postoperative year. This was not associated with WL. The impact of these results on hepatic outcomes such as non-alcoholic steatohepatitis and fibrosis progression requires further studies. In both groups, improved insulin resistance and sensitivity were correlated with higher WL and lower liver fat percentage, respectively. PMID- 27003704 TI - Mortality as an endpoint in studies in critically ill patients: a reappraisal of definitions. AB - The recent literature was critically reviewed reporting heterogeneous mortality endpoints in studies involving critically ill patients. Both location- and duration-dependent definitions are used, more or less arbitrarily and sometimes with contradictory results. Location-dependent mortality refers to intensive care or in-hospital mortality whereas duration-dependent mortality concerns 7-180 day mortality after admission or intervention. There is no consensus on how mortality should be evaluated in the critically ill. It is argued that trialists should aim at uniformity in outcome evaluation of critical care, in order to allow comparison of studies, and that 28-day mortality should remain the primary endpoint for intervention studies. PMID- 27003705 TI - Transverse myelitis associated with heroin and cannabis abuse: a new issue from the past. PMID- 27003702 TI - Linking habitat selection to fitness-related traits in herbivores: the role of the energy landscape. AB - Animals may partially overcome environmental constraints on fitness by behaviorally adjusting their exposure to costs and supplies of energy. Few studies, however, have linked spatiotemporal variation in the energy landscape to behaviorally mediated measures of performance that ostensibly influence individual fitness. We hypothesized that strength of selection by North American elk (Cervus elaphus) for areas that reduced costs of thermoregulation and activity, and increased access to high-quality forage, would influence four energetically mediated traits related to fitness: birth mass of young, nutritional condition of adult females at the onset of winter, change in nutritional condition of females between spring and winter, and neonatal survival. We used a biophysical model to map spatiotemporally explicit costs of thermoregulation and activity experienced by elk in a heterogeneous landscape. We then combined model predictions with data on forage characteristics, animal locations, nutritional condition, and mass and survival of young to evaluate behaviorally mediated effects of the energy landscape on fitness-related traits. During spring, when high-quality forage was abundant, female elk that consistently selected low-cost areas before parturition gave birth to larger young than less-selective individuals, and birth mass had a strong, positive influence on probability of survival. As forage quality declined during autumn, however, lactating females that consistently selected the highest quality forage available accrued more fat and entered winter in better condition than less selective individuals. Results of our study highlight the importance of understanding the dynamic nature of energy landscapes experienced by free-ranging animals. PMID- 27003709 TI - User-driven conversations about dialysis through Facebook: A qualitative thematic analysis. AB - AIM: As one of the most popular social networking sites in the world, Facebook has strong potential to enable peer support and the user-driven sharing of health information. We carried out a qualitative thematic analysis of the wall posts of a public Facebook group focused on dialysis to identify some of the major themes discussed. METHODS: We searched Facebook using the word 'dialysis'. A Facebook group (Dialysis Discussion Uncensored) with the highest number of members was selected amongst publicly available forums related to dialysis and operated in English (http://www.facebook.com/groups/DialysisUncensored). Two researchers independently extracted information on features of the group including purpose, group members and the user-generated posts on the group wall. Posts were further analysed to develop major themes. RESULTS: Characteristics of a Facebook group based on its participants and activities are presented. Three themes are described with representative quotations. In a period of 2 weeks, we found 1257 wall posts with total of 31 636 likes and 15 972 comments. All messages were in English, and the majority of the participants were dialysis patients. However, we observed the participation of family members and care providers as well. Posts were categorized into three major themes: sharing information, seeking and providing emotional and social support and sharing experience. CONCLUSION: Findings of this study provide an example of how a social networking platform can enable patients and their families to share information and to encourage peer based support for managing dialysis-related experiences. PMID- 27003707 TI - Development and validation of an enantioselective SFC-MS/MS method for simultaneous separation and quantification of oxcarbazepine and its chiral metabolites in beagle dog plasma. AB - A rapid and sensitive assay based on supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) has been developed and validated for the determination of oxcarbazepine (OXC) and its chiral metabolite licarbazine (Lic) in beagle dog plasma using carbamazepine as internal standard. Chiral analysis in a run time of only 3 min was performed on an ACQUITY UPC(2) TM TrefoilTM CEL2 column (3.0 * 150 mm, 2.5 MUm) at 50 degrees C by isocratic elution with a mobile phase of supercritical carbon dioxide (purity >= 99.99%) and methanol (60:40, v/v) at a flow rate of 2.3 mL/min. The assay was linear over the concentration ranges 5-1000 ng/mL for OXC and 0.5-100 ng/mL for the enantiomers of Lic with corresponding lower limits of quantitation of 5 ng/mL and 0.5 ng/mL. Intra- and inter-day precisions were in the range 0.78-14.14% with accuracies in the range -10.80% to 0.42%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of 16 mg/kg OXC as Trileptal(@) tablets to beagle dogs. PMID- 27003708 TI - MaxReport: An Enhanced Proteomic Result Reporting Tool for MaxQuant. AB - MaxQuant is a proteomic software widely used for large-scale tandem mass spectrometry data. We have designed and developed an enhanced result reporting tool for MaxQuant, named as MaxReport. This tool can optimize the results of MaxQuant and provide additional functions for result interpretation. MaxReport can generate report tables for protein N-terminal modifications. It also supports isobaric labelling based relative quantification at the protein, peptide or site level. To obtain an overview of the results, MaxReport performs general descriptive statistical analyses for both identification and quantification results. The output results of MaxReport are well organized and therefore helpful for proteomic users to better understand and share their data. The script of MaxReport, which is freely available at http://websdoor.net/bioinfo/maxreport/, is developed using Python code and is compatible across multiple systems including Windows and Linux. PMID- 27003706 TI - A Comparative Study of Orally Delivered PBCA and ApoE Coupled BSA Nanoparticles for Brain Targeting of Sumatriptan Succinate in Therapeutic Management of Migraine. AB - PURPOSE: The present investigation aimed at brain targeting of sumatriptan succinate (SS) for its optimal therapeutic effect in migraine through nanoparticulate drug delivery system using poly (butyl cyanoacrylate) (PBCA) and bovine serum albumin linked with apolipoprotein E3 (BSA-ApoE). METHOD: The study involved formulation optimization of PBCA nanoparticles (NPs) using central composite design for achieving minimum particle size, maximum entrapment efficiency along with sustained drug release. SS incorporated in BSA-ApoE NPs (S AA-NP) were prepared by desolvation technique and compared with SS loaded polysorbate 80 coated optimized PBCA NPs (FPopt) in terms of their brain uptake potential, upon oral administration in male Wistar rats. The NPs were characterized by FTIR, thermal, powder XRD and TEM analysis. RESULTS: The in vivo studies of FPopt and S-AA-NP on male Wistar rats demonstrated a fairly high brain/plasma drug ratio of 9.45 and 12.67 respectively 2 h post oral drug administration. The behavioural studies on male Swiss albino mice affirmed the enhanced anti-migraine potential of S-AA-NP than FPopt (P < 0.001). CONCLUSION: The results of this work, therefore, indicate that BSA-ApoE NPs are significantly better than polysorbate 80 coated PBCA NPs for brain targeting of SS (P < 0.05) and also offer an improved therapeutic strategy for migraine management. PMID- 27003703 TI - Neural Contributions to Muscle Fatigue: From the Brain to the Muscle and Back Again. AB - : During exercise, there is a progressive reduction in the ability to produce muscle force. Processes within the nervous system as well as within the muscles contribute to this fatigue. In addition to impaired function of the motor system, sensations associated with fatigue and impairment of homeostasis can contribute to the impairment of performance during exercise. This review discusses some of the neural changes that accompany exercise and the development of fatigue. The role of brain monoaminergic neurotransmitter systems in whole-body endurance performance is discussed, particularly with regard to exercise in hot environments. Next, fatigue-related alterations in the neuromuscular pathway are discussed in terms of changes in motor unit firing, motoneuron excitability, and motor cortical excitability. These changes have mostly been investigated during single-limb isometric contractions. Finally, the small-diameter muscle afferents that increase firing with exercise and fatigue are discussed. These afferents have roles in cardiovascular and respiratory responses to exercise, and in the impairment of exercise performance through interaction with the motor pathway, as well as in providing sensations of muscle discomfort. Thus, changes at all levels of the nervous system, including the brain, spinal cord, motor output, sensory input, and autonomic function, occur during exercise and fatigue. The mix of influences and the importance of their contribution vary with the type of exercise being performed. PMID- 27003711 TI - Atypical decelerations: do they matter? AB - OBJECTIVE: To estimate the association between atypical variable decelerations and neonatal acidemia. METHOD: We conducted a one-year case-control study comparing the last thirty minutes before delivery of fetal heart rate tracings of 102 acidemic neonates (umbilical arterial cord gas pH <= 7.10) with 100 non acidemic controls (umbilical arterial cord gas pH > 7.10). Incidence of atypical features and total number of decelerations, number of atypical decelerations, number of slow return decelerations and number of decelerations with loss of moderate variability during deceleration were extracted. We estimated the association between atypical features, neonatal acidemia and neonatal morbidity. RESULTS: Acidemic neonates showed a larger number of atypical decelerations (4 [0 12] vs. 3 [0-10]), "slow return" decelerations (4 [0-11] vs. 1 [0-10]) and decelerations with non-moderate variability (0[0-12] vs. 0 [0-6]) compared to non acidemic controls. "Slow return" was significantly associated with an increased risk of acidemia at birth (OR 4.46; CI 95%: 2.18 - 9.15) "Slow return" was the most discriminating feature between groups with an AUC: 0.745. CONCLUSION: Certain atypical features, as "slow return" and loss of moderate variability within decelerations are associated with neonatal acidemia. "Slow return" could help in the gradation of acidemia risk levels, as an indicator of gravity. PMID- 27003710 TI - Permissible Home Range Estimation (PHRE) in Restricted Habitats: A New Algorithm and an Evaluation for Sea Otters. AB - Parametric and nonparametric kernel methods dominate studies of animal home ranges and space use. Most existing methods are unable to incorporate information about the underlying physical environment, leading to poor performance in excluding areas that are not used. Using radio-telemetry data from sea otters, we developed and evaluated a new algorithm for estimating home ranges (hereafter Permissible Home Range Estimation, or "PHRE") that reflects habitat suitability. We began by transforming sighting locations into relevant landscape features (for sea otters, coastal position and distance from shore). Then, we generated a bivariate kernel probability density function in landscape space and back transformed this to geographic space in order to define a permissible home range. Compared to two commonly used home range estimation methods, kernel densities and local convex hulls, PHRE better excluded unused areas and required a smaller sample size. Our PHRE method is applicable to species whose ranges are restricted by complex physical boundaries or environmental gradients and will improve understanding of habitat-use requirements and, ultimately, aid in conservation efforts. PMID- 27003712 TI - Keratoneuritis is not pathognomonic of Acanthamoeba keratitis: a case report of Pseudomonas keratitis. AB - The presence of keratoneuritis in a radial pattern is considered to be a virtually pathognomonic sign of Acanthamoeba keratitis. We report a case of a massive keratoneuritis as a presenting sign in Pseudomonas keratitis in a contact lens wearer, thereby further challenging this concept. PMID- 27003714 TI - Pulsatility Index quantification in the human precapillary arterioles of the eye. AB - The Pulsatility Index (PI) was quantified for the first time in the human conjunctival pre-capillary arterioles in vivo. In 30 arterioles with diameters ranging between 6 and 12MUm, from 15 healthy humans, peak to peak velocity ranged from 0.2 up to 4.8mm/s with a mean value equal to 1.4+/-0.2 (SE) mm/s. The PI ranged from 0.4 to 1.5 and the overall mean value was 0.8+/-0.1 (SE). The linear correlation between PI and diameter was practically zero (Spearman's correlation coefficient, rs~0) for the range of arteriolar diameters examined here. In this work a first step was made towards the complete PI mapping of the human carotid arterial tree. PMID- 27003713 TI - Serum uric acid as a marker of microvascular damage in systemic sclerosis patients. AB - BACKGROUND: Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease. METHODS: Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured. RESULTS: The serum UA showed a significant positive correlation with sCr (r=0.33, p<0.0001) and PAPs (r=0.38, p<0.01) >and negative correlation with CKD-EPI (r= 0.35, p<0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p<0.05) in SSc patients with low normal or high normal serum UA. CONCLUSIONS: Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies. PMID- 27003717 TI - Hydrogen sensing via anomalous optical absorption of palladium-based metamaterials. AB - A palladium (Pd)-based optical metamaterial has been designed, fabricated and characterized for its application in hydrogen sensing. The metamaterial can replace Pd thin films in optical transmission schemes for sensing with performances far superior to those of conventional sensors. This artificial material consists of a palladium-alumina metamaterial fabricated using inexpensive and industrial-friendly bottom-up techniques. During the exposure to hydrogen, the system exhibits anomalous optical absorption when compared to the well-known response of Pd thin films, this phenomenon being the key factor for the sensor sensitivity. The exposure to hydrogen produces a large variation in the light transmission through the metamembrane (more than 30% with 4% in volume hydrogen-nitrogen gas mixture at room temperature and atmospheric pressure), thus avoiding the need for sophisticated optical detection systems. An optical homogenization model is proposed to explain the metamaterial response. These results contribute to the development of reliable and low-cost hydrogen sensors with potential applications in the hydrogen economy and industrial processes to name a few, and also open the door to optically study the hydrogen diffusion processes in Pd nanostructures. PMID- 27003715 TI - Altering Visual Perception Abnormalities: A Marker for Body Image Concern. AB - The body image concern (BIC) continuum ranges from a healthy and positive body image, to clinical diagnoses of abnormal body image, like body dysmorphic disorder (BDD). BDD and non-clinical, yet high-BIC participants have demonstrated a local visual processing bias, characterised by reduced inversion effects. To examine whether this bias is a potential marker of BDD, the visual processing of individuals across the entire BIC continuum was examined. Dysmorphic Concern Questionnaire (DCQ; quantified BIC) scores were expected to correlate with higher discrimination accuracy and faster reaction times of inverted stimuli, indicating reduced inversion effects (occurring due to increased local visual processing). Additionally, an induced global or local processing bias via Navon stimulus presentation was expected to alter these associations. Seventy-four participants completed the DCQ and upright-inverted face and body stimulus discrimination task. Moderate positive associations were revealed between DCQ scores and accuracy rates for inverted face and body stimuli, indicating a graded local bias accompanying increases in BIC. This relationship supports a local processing bias as a marker for BDD, which has significant assessment implications. Furthermore, a moderate negative relationship was found between DCQ score and inverted face accuracy after inducing global processing, indicating the processing bias can temporarily be reversed in high BIC individuals. Navon stimuli were successfully able to alter the visual processing of individuals across the BIC continuum, which has important implications for treating BDD. PMID- 27003716 TI - Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation. AB - BACKGROUND: Genetic associations of the response to inhaled corticosteroids (ICSs) during an asthma exacerbation are unknown. OBJECTIVE: To evaluate the role of genetic variants in the therapeutic response to high-dose ICS in children with moderate-to-severe asthma exacerbations. METHODS: Eighty-two children (56 boys/26 girls, mean age 9.6 +/- 3.2 years) with moderate-severe asthma exacerbation were genotyped for eight single-nucleotide polymorphisms that were a priori associated with ICS response in chronic asthma treatment: glucocorticosteroid receptor (NR3C1) rs41423247; corticotrophin-releasing hormone receptor1 (CRHR1) rs242939, rs242941, and rs1876828; T-box 21 (TBX21) rs2240017; glucocorticoid-induced transcript 1 (GLCCl1); and T gene rs3099266 and rs2305089. Children were treated with a single high-dose (4000 MUg) fluticasone propionate given by a nebulizer followed by 1000 MUg/day of inhaled fluticasone propionate for 6 days. Primary outcome measure was the improvement in FEV1 at 4 h. RESULTS: Mean FEV1 was 71.7 +/- 14.2% at presentation. Overall, fluticasone treatment resulted in a significant improvement in asthma score and FEV1 (p < 0.0001 for both). Children with the GG genotype at NR3C1 rs41423247 (n = 26) had a higher improvement in FEV1 [24.2% (interquartile range 11.5-36.3)] compared to those with CG+CC (n = 19), [7.9% (interquartile range 6.1-24.6) (p = 0.006)]. CONCLUSION: Homozygosity for the G allele at rs41423247 of the glucocorticosteroid receptor (NR3C1) gene is associated with a higher improvement in FEV1 at 4 h in children with moderate to-severe asthma exacerbation treated with high-dose ICS. This observation may have important clinical implications especially for children who use systemic steroids frequently for recurrent asthma exacerbations. PMID- 27003718 TI - Pharmaceuticals in the environment: An introduction to the ET&C special issue. PMID- 27003719 TI - Effects of trophic exposure to diclofenac and dexamethasone on hematological parameters and immune response in freshwater fish. AB - The aim of the present study was to evaluate the effects of diclofenac and dexamethasone on hematological parameters and immune response in the fish species Hoplias malabaricus after trophic exposure. Fish were fed twice every week with Astyanax sp., which were given an intraperitoneal inoculation with diclofenac (0 MUg/kg, 0.2 MUg/kg, 2.0 MUg/kg, or 20.0 MUg/kg) or dexamethasone (0.03 MUg/kg, 0.3 MUg/kg, or 3.0 MUg/kg). After 12 doses, the hematological parameters and lipopolysaccharide-induced nitric oxide production by head kidney monocytic lineage were evaluated. Exposed fish also received 1 mg/kg of carrageenan intraperitoneal, and cell migration to the peritoneal cavity was evaluated after 4 h. Diclofenac and dexamethasone altered the red blood cell count, as well as hematocrit and hemoglobin levels. The total blood leukocyte count decreased in all groups. A significantly reduced carrageenan-induced leukocyte migration to the peritoneal cavity, particularly of polymorphonuclear cells, was observed at all tested doses, suggesting a possible immunosuppressive effect. The basal nitric oxide synthesis of head kidney cell cultures was reduced at the highest dose of diclofenac and was increased at the highest dose of dexamethasone. The lipopolysaccharide-stimulated nitric oxide production was reduced in all treatments, thus corroborating the immunosuppressive effect. Although some fish responses were variable for different drugs, the results suggested that trophic exposure to diclofenac and dexamethasone can lead to hematological changes and immunotoxic effects, causing negative impacts in aquatic organisms. PMID- 27003720 TI - Predicted and observed therapeutic dose exceedances of ionizable pharmaceuticals in fish plasma from urban coastal systems. AB - Instream flows of the rapidly urbanizing watersheds and estuaries of the Gulf of Mexico in Texas (USA) are increasingly dominated by reclaimed waters. Though ionizable pharmaceuticals have received increasing attention in freshwaters, many research questions remain unanswered, particularly in tidally influenced urban coastal systems, which experience significant spatiotemporal variability in pH that influences bioavailability and bioaccumulation. The authors coupled fish plasma modeling of therapeutic hazard values with field monitoring of water chemistry variability and pharmaceutical occurrence to examine whether therapeutic hazards to fish existed within these urban coastal ecosystems and whether therapeutic hazards differed within and among coastal locations and seasons. Spatial and temporal fluctuations in pH within study sites altered the probability of encountering pharmaceutical hazards to fish. Significant water quality differences were consistently observed among traditional parameters and pharmaceuticals collected from surface and bottom waters, which are rarely sampled during routine surface water quality assessments. The authors then compared modeling predictions of fish plasma concentrations of pharmaceuticals to measured plasma levels from various field-collected fish species. Diphenhydramine and diltiazem were observed in plasma of multiple species, and diltiazem exceeded human therapeutic doses in largemouth bass, catfish, and mullet inhabiting these urban estuaries. Though the present study only examined a small number of target analytes, which represent a microcosm of the exposome of these fish, coastal systems are anticipated to be more strongly influenced by continued urbanization, altered instream flows, and population growth in the future. Unfortunately, aquatic toxicology information for diltiazem and many other pharmaceuticals is not available for marine and estuarine organisms, but such field observations suggest that potential adverse outcomes should be examined. PMID- 27003721 TI - Kinetic and Mechanistic Aspects of the Reactions of Iodide and Hypoiodous Acid with Permanganate: Oxidation and Disproportionation. AB - Oxidation kinetics of iodide and HOI/OI(-) by permanganate were studied in the pH range of 5.0-10.0. Iodide oxidation and iodate formation were faster at lower pH. The apparent second-order rate constants (k(obs)) for iodide oxidation by permanganate decrease with increasing pH from 29 M(-1) s(-1) at pH 5.0 and 6.9 M( 1) s(-1) at pH 7.0 to 2.7 M(-1) s(-1) at pH 10.0. k(obs) for HOI abatement are 56 M(-1) s(-1) at pH 5.0, 2.5 M(-1) s(-1) at pH 7.0, and 173 M(-1) s(-1) at pH 10.0. Iodate yields over HOI abatement decrease from 98% at pH 6.0 to 33% for pH >= 9.5, demonstrating that HOI disproportionation dominates HOI transformation by permanganate at pH >= 8.0. MnO2 formed as a product from permanganate reduction, oxidizes HOI to iodate for pH < 8.0, and promotes HOI disproportionation for pH >= 8.0. The rate of HOI oxidation or disproportionation induced by MnO2 is much lower than for permanganate. During treatment of iodide-containing waters, the potential for iodinated disinfection byproducts (I-DBPs) formation is highest at pH 7.0-8.0 due to the long lifetime of HOI. For pH < 6.0, HOI/I2 is quickly oxidized by permanganate to iodate, whereas for pH >= 8.0, HOI/OI(-) undergoes a fast permanganate-mediated disproportionation. PMID- 27003722 TI - Odorant Receptors of the New Zealand Endemic Leafroller Moth Species Planotortrix octo and P. excessana. AB - Moths use their sense of smell to find food sources, mating partners and oviposition sites. For this they possess a family of odorant receptors (ORs). Some ORs are used by both sexes whereas others have sex-specific roles. For example, male moths possess ORs specifically tuned to sex pheromones produced by conspecific females. Here we identify sets of ORs from the antennae of New Zealand endemic leafroller moths Planotortrix octo (48 ORs) and P. excessana (47 ORs) using an RNA-Seq approach. Two orthologous ORs show male-biased expression in the adult antennae of both species (OR7 and OR30) and one other OR in each species was female-biased in its expression (PoctOR25, PexcOR14) by qPCR. PAML analysis conducted on male-biased ORs indicated positive selection acting on the male-biased OR7. The fact that OR7 is likely under positive selection, that it is male-biased in its expression and that its orthologue in C. obliquana, CoblOR7, responds to sex pheromone components also utilised by Planotortrix species, suggests that this receptor may also be important in sex pheromone reception in Planotortrix species. PMID- 27003723 TI - Mitochondrial autophagy in cardiomyopathy. AB - Cardiac mitochondria produce vast amounts of ATP through oxidative phosphorylation to maintain contractile function. They are also the primary source of reactive oxygen species, which contribute to mitochondrial dysfunction, cardiomyocyte death, and heart failure. To protect against mitochondrial damage, cardiomyocytes develop well-coordinated quality control mechanisms that maintain the overall mitochondrial health through mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy (mitophagy). Mitophagy removes dysfunctional mitochondria in the heart not only under normal physiological conditions, but also in response to pathological stresses. Accumulating evidence suggests that mitophagy dysregulation can induce cardiomyocyte death and cardiomyopathy. In this review, we discuss what is currently known about mitophagic mechanisms, regulatory pathways, and function in the heart. PMID- 27003726 TI - Antimony(III) Sulfide Thin Films as a Photoanode Material in Photocatalytic Water Splitting. AB - For the first time, we present exploratory investigations on the performance of thermally evaporated Sb2S3 thin film photoanodes for solar-assisted water splitting applications. With a band gap of 1.72 eV, a 250 nm thick Sb2S3 photoanode showed a saturation photocurrent density of ~600 MUA cm(-2) measured at 1.0 V reversible hydrogen electrode (RHE) in 0.1 M Na2SO4 under 1-sun illumination, with an onset potential of ~0.25 V RHE. However, subsequent photodegradation studies revealed that the material dissolves relatively quickly with the application of both illumination and bias. Nonetheless, Sb2S3 does have the advantage of having a relatively low optimal fabrication temperature of 300 degrees C and thus may have utility as a top cell absorber of a tandem device where the bottom cell is temperature sensitive, if protected from corrosion. Therefore, we characterized relevant aspects of the material in an attempt to explain the large difference between the theoretical maximum and measured current density. From our characterization it is believed that the photocatalytic efficiency of this material can be improved by modifying the surface to reduce optical reflection and addressing inherent issues such as high electrical resistivity and surface defects. PMID- 27003727 TI - Kinetic and Binding Studies of Streptococcus pneumoniae Type 2 Isopentenyl Diphosphate:Dimethylallyl Diphosphate Isomerase. AB - Type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase (IDI-2) converts isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP), the two fundamental building blocks of isoprenoid molecules. IDI-2 is found in many species of bacteria and is a potential antibacterial target since this isoform is non-homologous to the type 1 enzyme in Homo sapiens. IDI-2 requires a reduced flavin mononucleotide to form the catalytically active ternary complex, IDI 2.FMNH2.IPP. For IDI-2 from the pathogenic bacterium Streptococcus pneumoniae, the flavin can be treated kinetically as a dissociable cosubstrate in incubations with IPP and excess NADH. Under these conditions, the enzyme follows a modified sequential ordered mechanism where FMN adds before IPP. Interestingly, the enzyme shows sigmoidal behavior when incubated with IPP and NADH with varied concentrations of FMN in aerobic conditions. In contrast, sigmoidal behavior is not seen in incubations under anaerobic conditions where FMN is reduced to FMNH2 before the reaction is initiated by addition of IPP. Stopped-flow experiments revealed that FMN, whether bound to IDI-2 or without enzyme in solution, is slowly reduced in a pseudo-first-order reaction upon addition of excess NADH (k(red)(FMN) = 5.7 * 10(-3) s(-1) and k(red)(IDI-2.FMN) = 2.8 * 10(-3) s(-1)), while reduction of the flavin is rapid upon addition of NADH to a mixture of IDI 2.FMN, and IPP (k(red)(IDI-2.FMN.IPP) = 8.9 s(-1)). Similar experiments with dithionite as the reductant gave k(red)(FMN) = 221 s(-1) and k(red)(IDI-2.FMN) = 411 s(-1). Dithionite reduction of FMN in the IDI-2.FMN and IPP mixture was biphasic with k(red)(IDI-2.FMN.IPP (fast)) = 326 s(-1) and k(red)(IDI-2.FMN.IPP (slow)) = 6.9 s(-1) The pseudo-first-order rate constant for the slow component was similar to those for NADH reduction of the flavin in the IDI-2.FMN and IPP mixture and may reflect a rate-limiting conformational change in the enzyme. PMID- 27003724 TI - TP53 mutation, mitochondria and cancer. AB - Under normal conditions, basal levels of wild-type p53 promote mitochondrial function through multiple mechanisms. Remarkably, some missense mutations of p53, in contrast to the null state, can result in the retention of its metabolic activities. These effects are particularly prominent in the mitochondria and demonstrate a functional role for mutant p53 in cancer metabolism. This review summarizes accumulating data on the mechanisms by which p53 missense mutations can regulate mitochondrial metabolism and promote the viability and survival of both normal and cancer cells, thus acting as a double edged sword for the host. Greater understanding of these mechanisms may provide insights for developing new treatment or preventive strategies against cancer. PMID- 27003729 TI - Planning an organizational wellness initiative at a multi-state social service agency. AB - Increasingly, organizations in general, and social service organizations, specifically, are recognizing the importance of planning and evaluating organizational wellness initiatives. Yet, few participatory models for carrying out these aims exist. For this study, researchers utilized concept mapping (CM) to explicate a conceptual framework for planning, and subsequently evaluating, a wellness initiative at a multi-state social service organization. CM is a participatory approach that analyzes qualitative data via multi-dimensional scaling and hierarchical cluster analyses. Outputs include a number of visual depictions that allow researchers to explore complex relationships among sets of the data. Results from this study indicated that participants (N=64), all of whom were employees of the agency, conceptualized organizational wellness via an eight cluster solution, or Concept Map. Priority areas of this framework, specifically importance and feasibility, were also explored. After a brief review of pertinent literature, this article explicates the CM methodology utilized in this study, describes results, discusses lessons learned, and identifies apt areas for future research. PMID- 27003728 TI - Antiproliferative and Proapoptotic Effects of Crocin Combined with Hyperthermia on Human Breast Cancer Cells. AB - We investigated the suppressive effects of crocin alone and in combination with hyperthermia (HT) on proliferation of breast cancer cells. Cell viability, colony formation ability, and apoptosis were assessed by 3-(4,5-dimetylthiazol-2-Yl)-2,5 diphenyltetrazolium bromide (MTT), soft agar, Hoechst 33258 staining, and percentage of lactate dehydrogenase (LDH) release methods, respectively. The mRNA levels Hsp27, Hsp70, Hsp90, Bax, and Bcl-2 were measured by quantitative real time polymerase chain reaction (qRT-PCR). Hsp70 and Hsp90 proteins were determined using enzyme-linked immunosorbent assay (ELISA) technique. Crocin in combination with HT significantly inhibited the proliferation of cancer cells in a dose- and time-dependent manner. There was a degree of synergism in the combined treatment. However, crocin did not show the high cytotoxic effect on normal cells. This treatment decreased colony formation of cancer cells up to 94%. Changed nuclear morphology and increased LDH indicated that crocin combined with HT has a more apoptotic effect than crocin alone. Furthermore, in treated cells Bax/Bcl-2 ratio markedly increased, whereas expression of heat-induced genes decreased. Also, the Hsp70 and Hsp90 proteins decreased in the treated cells. Our study indicated that combination of crocin and HT has strong antiproliferative and apoptotic activities against breast cancer cells. Hence, it is suggested that more studies are warranted to apply crocin as a possible, safe, and promising anticancer agent in cancer. PMID- 27003730 TI - Planning an integrated agriculture and health program and designing its evaluation: Experience from Western Kenya. AB - Multi-sectoral programs that involve stakeholders in agriculture, nutrition and health care are essential for responding to nutrition problems such as vitamin A deficiency among pregnant and lactating women and their infants in many poor areas of lower income countries. Yet planning such multi-sectoral programs and designing appropriate evaluations, to respond to different disciplinary cultures of evidence, remain a challenge. We describe the context, program development process, and evaluation design of the Mama SASHA project (Sweetpotato Action for Security and Health in Africa) which promoted production and consumption of a bio fortified, orange-fleshed sweetpotato (OFSP). In planning the program we drew upon information from needs assessments, stakeholder consultations, and a first round of the implementation evaluation of a pilot project. The multi-disciplinary team worked with partner organizations to develop a program theory of change and an impact pathway which identified aspects of the program that would be monitored and established evaluation methods. Responding to the growing demand for greater rigour in impact evaluations, we carried out quasi-experimental allocation by health facility catchment area, repeat village surveys for assessment of change in intervention and control areas, and longitudinal tracking of individual mother child pairs. Mid-course corrections in program implementation were informed by program monitoring, regular feedback from implementers and partners' meetings. To assess economic efficiency and provide evidence for scaling we collected data on resources used and project expenses. Managing the multi-sectoral program and the mixed methods evaluation involved bargaining and trade-offs that were deemed essential to respond to the array of stakeholders, program funders and disciplines involved. PMID- 27003731 TI - Macular Ganglion Cell-Inner Plexiform Layer and Retinal Nerve Fiber Layer Thickness in Eyes With Primary Open-Angle Glaucoma Compared With Healthy Saudi Eyes: A Cross-Sectional Study. AB - PURPOSE: We compared the thickness of the ganglion cell-inner plexiform layer at the macula (mGCIPL) and the thickness of the retinal nerve fiber layer (RNFL) in different regions of the retina in eyes with primary open-angle glaucoma (POAG group) and normal eyes (control group). DESIGN: This was a cross-sectional study performed in 2014. METHODS: Spectral domain optical coherence tomography (SD-OCT) was used to measure mGCIPL and RNFL thickness. Age-adjusted means and standard deviation were calculated. Age, sex, refractive status, corneal thickness, and stage/severity of glaucoma (defined by vertical cup-to-disc ratio and visual field changes) were associated to outcomes. Statistical significance was indicated by P < 0.05. RESULTS: There were 50 eyes in the POAG group and 52 eyes in the control group. The difference in age between patients in both groups was statistically significant (P < 0.001). The age-adjusted measurements were thinner for POAG with a mean difference (DF) of 11.1 MUm for mGCIPL and 8 MUm for mRNFL. The mGCIPL to mRFNL ratio was 2.1 in the POAG group and 1.9 in the control group (degrees of freedom = 0.2, P = 0.001). The mGCIPL and RNFL thickness decreased as the severity of glaucoma increased. The mGCIPL to mRNFL ratio was a predictor of the severity of field defects in POAG (AUROC = 0.66, P = 0.0002). Age and myopia were confounders to the association of OCT findings and the visual field changes in POAG (P = 0.07). CONCLUSIONS: There was generalized thinning of retinal layers in eyes of nondiabetic Arab patients with POAG. OCT parameters can be important for detecting and monitoring glaucoma cases. PMID- 27003732 TI - Diagnosis, Management, and Histopathological Characteristics of Corneal Keloid: A Case Series and Literature Review. AB - PURPOSE: Corneal keloids are rare lesions that develop in cases of corneal insult. We describe the clinical features, subsequent management, and histopathological characteristics of 5 of our cases of corneal keloid. DESIGN: This was an interventional case series. METHODS: A total of 5 patients were examined and treated for corneal keloid. RESULTS: Five Indian patients with no keloids on the skin or any history of hypertrophic scar formation complained of progressive painless dimness of vision and a slowly growing epicorneal mass. There was a history of traumatic cataract extraction with anterior chamber intraocular lens implantation in 2 of the cases, corneal decompensation after viral keratouveitis in the third case, a history of penetrating injury in the fourth, and a history of anterior stromal puncture for bullous keratopathy in the last case. On examination, a pearly white glistening mass occupying almost the entire cornea was seen in all. Treatment options considered were superficial keratectomy with amniotic membrane transplantation and lamellar and penetrating keratoplasty. Histopathological features in all patients were consistent with a diagnosis of corneal keloid. Immunohistochemical stain was positive for vimentin. CONCLUSIONS: Corneal keloid should be suspected in cases of enlarging white glistening corneal scar after trauma. Although unusual, it can also appear after corneal infections that serve as persistent stimuli to the repair process. Management options are varied as outlined previously. PMID- 27003733 TI - Physical Activity, Sedentary Behaviors, and Retinal Vascular Caliber in Children and Adolescents With Type 1 Diabetes. AB - PURPOSE: The aim of this study was to investigate associations of physical activity and sedentary behaviors with retinal vascular caliber in children and adolescents with type 1 diabetes. DESIGN: This was a hospital-based cross sectional study. METHODS: A study of 122 children and adolescents with type 1 diabetes was conducted over an 8-month period. Self-reported physical activity time and time spent watching TV or playing computer or video games were obtained using interviewer-administered questionnaires. Retinal vascular caliber was measured by a trained grader using a standardized protocol and later summarized as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) using a semiautomated computer program. RESULTS: After adjusting for confounders (age, sex, ethnicity, body mass index, systolic blood pressure, HbA1c, maternal smoking status, age at which cow's milk was introduced, and CRVE/CRAE, respectively), narrower CRAE was independently related to more time spent playing computer/video games [ExpB = -3.85; 95% confidence interval (CI), 6.41 to -1.29; P = 0.004], whereas wider CRVE was independently related to lower physical activity level (ExpB = -1.08; 95% CI, -2.01 to -0.15; P = 0.03) and more time spent playing computer/video games (ExpB = 4.72; 95% CI, 0.52-8.92; P = 0.02). Television viewing time was not associated with retinal vascular caliber after adjustment. CONCLUSIONS: The results of this study suggest that physical activity and sedentary behaviors in the form of "screen viewing time" are associated with retinal vessel caliber early in life. These results suggest that retinal vascular caliber may provide prognostic information beyond current traditional cardiovascular risk factors. Future longitudinal and interventional studies are warranted to evaluate the relevance of these observations. PMID- 27003734 TI - Endophthalmitis After Pars Plana Vitrectomy: Clinical Features, Risk Factors, and Management Outcomes. AB - PURPOSE: To report the clinical presentations, risk factors, and outcomes of endophthalmitis after pars plana vitrectomy at 4 tertiary eye care centers of an institute in South India. DESIGN: A retrospective case series. METHODS: The records of 38,591 patients undergoing vitrectomy were reviewed using the coding assigned by the medical records department. Consecutive cases diagnosed as endophthalmitis after pars plana vitrectomy (PPV) between 1990 and 2014 for various indications were analyzed. RESULTS: The clinical incidence of postvitrectomy endophthalmitis was 0.052%, and culture-positive incidence of postvitrectomy endophthalmitis was 0.031%. Twelve cases (60%) were culture positive. Mean presenting vision was 2.16 +/- 1.51 logMAR (Snellen equivalent 20/2890). Seventeen eyes had received sutureless vitreous surgery (15 cases 23G, 2 cases 25G) and 3 eyes had received 20G suture-assisted vitreous surgery (P < 0.0001). The odds of developing endophthalmitis in sutureless versus sutured vitrectomy were 25.14 [95% confidence interval (CI), 7.37-85.84] (P < 0.0001) and those of developing endophthalmitis in sutureless surgery versus sutured with final tamponade of Ringer lactate (RL) were 19.53 (95% CI, 5.37-71.03) (P < 0.0001). In sutureless surgeries, the odds of developing endophthalmitis in RL tamponaded eyes versus non-RL ones was 4.39 (95% CI, 1.67-11.56) (P = 0.002). Mean interval between vitreous surgery and endophthalmitis was 4 +/- 6.89 days; median, 1.5 days. Mean postoperative vision was 1.7 +/- 1.36 logMAR (Snellen equivalent 20/1002) (P = 0.31). CONCLUSIONS: Endophthalmitis after vitrectomy is an acute presentation. Sutureless surgery, especially with aqueous tamponade, has a higher risk. The visual outcome is relatively poor. PMID- 27003735 TI - Bilateral Herpes Simplex Uveitis: Review of the Literature and Own Reports?. AB - PURPOSE: Herpes simplex-associated uveitis is usually considered a unilateral eye disease, and rarely included in the differential diagnosis whenever there is bilateral involvement. We report three cases of bilateral herpetic anterior uveitis. METHODS: We evaluated three patients who presented with clinical manifestations of bilateral uveitis suggestive of viral origin. RESULTS: We found intraocular hypertension, cells in the anterior chamber, paralytic mydriasis, iris atrophy with transillumination defects, and variable anterior vitreous cellularity. According to the clinical findings, supported with herpes-specific antibody titers and aqueous humor PCR results in two of them, they were diagnosed with bilateral anterior herpetic uveitis. CONCLUSIONS: Our patients were initially misdiagnosed as having non-infectious uveitis and were treated with immunomodulatory medications, which could have favored the extension of infection bilaterally. Although uncommon, bilateral herpetic uveitis should always be considered in the differential diagnoses, when patients present with hypertensive uveitis in both eyes. PMID- 27003736 TI - Early tissue formation on whole-area osteochondral defect of rabbit patella by covering with fibroin sponge. AB - Large osteochondral defects have been difficult to repair via tissue engineering treatments due to the lack of a sufficient number of source cells for repairing the defect and to the severe mechanical stresses affecting the replacement tissue. In the present study, whole-area osteochondral defects of rabbit patella were covered and wrapped with a fibroin sponge containing chondrocytes, with or without Green Fluorescent Protein (GFP) transgenic marking, on the surface facing the osteochondral defect. Five of eight osteochondral defects that were covered with the chondrocyte-seeded fibroin sponges showed hyaline cartilage-like repair containing no fibroin fragments at 6 weeks after surgery. The repaired tissue showed a layer formation, which showed intensive safranin-O and toluidine blue staining, and which showed positive type II collagen immunostaining. The average surface coverage of the repaired cartilage was 53%. On average, 48% of the cells in the repaired tissue were derived from GFP transgenic chondrocytes, which had been seeded in the fibroin sponge. The fibroin-sponge covering had the potential to allow the early repair of large osteochondral defects. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1474-1482, 2016. PMID- 27003737 TI - The dental curing light: A potential health risk. AB - Powerful blue-light emitting dental curing lights are used in dental offices to photocure resins in the mouth. In addition, many dental personnel use magnification loupes. This study measured the effect of magnification loupes on the "blue light hazard" when the light from a dental curing light was reflected off a human tooth. Loupes with 3.5x magnification (Design for Vision, Carl Zeiss, and Quality Aspirator) and 2.5x magnification (Design for Vision and Quality Aspirator) were placed at the entrance of an integrating sphere connected to a spectrometer (USB 4000, Ocean Optics). A model with human teeth was placed 40 cm away and in line with this sphere. The light guide tip of a broad-spectrum Sapphire Plus (Den-Mat) curing light was positioned at a 45 degrees angle from the facial surface of the central incisor. The spectral radiant power reflected from the teeth was recorded five times with the loupes over the entrance into the sphere. The maximum permissible cumulative exposure times in an 8-hr day were calculated using guidelines set by the ACGIH. It was concluded that at a 40 cm distance, the maximum permissible cumulative daily exposure time to light reflected from the tooth was approximately 11 min without loupes. The weighted blue irradiance values were significantly different for each brand of loupe (Fisher's PLSD p < 0.05) and were up to eight times greater at the pupil than when loupes were not used. However, since the linear dimensions of the resulting images would be 2.5 to 3.5x larger on the retina, the image area was increased by the square of the magnification and the effective blue light hazard was reduced compared to without the loupes. Thus, although using magnification loupes increased the irradiance received at the pupil, the maximum cumulative daily exposure time to reflected light was increased up to 28 min. Further studies are required to determine the ocular hazards of a focused stare when using magnification loupes and the effects of other curing lights used in the dental office. PMID- 27003738 TI - Quantifying Risk Factors for Long-Term Sleep Problems After Burn Injury in Young Adults. AB - Restorative sleep is an important component of quality of life. Disturbances in sleep after burn injury were reported but all based on uncontrolled or nonstandardized data. The occurrence and the effect of long-term sleep problems in young adult burn survivors have not been well defined. This 5-year (2003-2008) prospective multicenter longitudinal study included adults with burn injuries ages 19 to 30 years who completed the Young Adult Burn Outcome Questionnaire (YABOQ) up to 36 months after injury. The items measured 15 patient-reported outcomes including physical, psychological, and social statuses and symptoms such as itch and pain. Scores of these 15 YABOQ outcome domains were standardized to a mean of 50 and a SD of 10 based on an age-matched nonburned reference group of young adults. Sleep quality was assessed using the item 'How satisfied are you now with your sleep,' rated by a 5-point Likert scale. Patients responding with very and somewhat dissatisfied were classified as having sleep dissatisfaction and the remaining as less or not dissatisfied. The associations between sleep dissatisfaction (yes/no) and YABOQ outcome domains were analyzed longitudinally using mixed-effect generalized linear models, adjusted for %TBSA burned, age, gender, and race. Generalized estimating equations were used to take into account correlated error resulting from repeated surveys on each patient over time. One hundred and fifty-two burn survivors participated in the YABOQ survey at baseline and during the follow-up who had at least one survey with a response to the sleep item. Among them, sleep dissatisfaction was twice as prevalent (76/152, 50%) when compared with the nonburned reference group (29/112, 26%). The likelihood of a burn survivor being dissatisfied with sleep was reduced over time after the burn injury. Sleep dissatisfaction following burns was significantly associated, in a dose-dependent manner, with increasing burn size (P = .001). Better sleep was associated with better outcomes in all domains (P < .05) except Fine Motor Function, and this association was significantly more apparent in the longer term compared with the shorter term with the same domains (P < .05). Dissatisfaction with sleep is highly prevalent following burn injuries in young adults. Lower satisfaction with sleep is associated with poorer scores in nearly all quality of life measures. Satisfaction with sleep should be addressed during the long-term clinical follow-up of young adults with burn injuries. Further research should be undertaken to understand the components of sleep quality that are important to burn survivors and which ones might be modified and tested in future intervention studies. PMID- 27003739 TI - A Review of Monocytes and Monocyte-Derived Cells in Hypertrophic Scarring Post Burn. AB - Pediatric burns remain a common injury after which many patients develop a severe form of scarring known as hypertrophic scarring. The formation of the hypertrophic scar arises from excessive production of collagen during wound healing. Wound repair and regeneration represents a complex process that is accomplished through many biological processes involving various cell types, extracellular matrix proteins, cytokines, and other mediators. One important cell type is the monocyte, which displays an altered profile in many wound models. These profile changes may function as biomarkers, reflecting and/or influencing the clinical outcome of the healing response seen after burn injury. Monocytes circulate in the blood and then enter into the tissue, where they further differentiate into macrophages, which serve various functions, including immune defense and tissue remodeling. More recently, these cells have been characterized in detail based on cell surface markers expressed and genes up-regulated, enabling subpopulations to be identified. Fibrocytes, which are also monocyte derived cells, have been shown to contribute to collagen production in the burn wound and are associated with hypertrophic scarring. They may represent a unique subpopulation of macrophages that, due to their production of collagen, promote tissue fibrosis rather than wound repair. A better understanding of the relationship among monocytes, fibrocytes, and macrophages may improve our appreciation of the factors influencing scar formation and tissue remodeling. PMID- 27003741 TI - Correction: Surprising impact of remote groups on the folding-unfolding and dimer chain equilibria of bifunctional H-bonding unimers. AB - Correction for 'Surprising impact of remote groups on the folding-unfolding and dimer-chain equilibria of bifunctional H-bonding unimers' by Rui Liu et al., Chem. Commun., 2016, 52, 3773-3776. PMID- 27003740 TI - Back Grafting the Split-Thickness Skin Graft Donor Site. AB - Split-thickness skin grafting is a useful method of wound repair in burn and reconstructive operations. However, skin grafts require a donor site injury that creates a secondary wound at risk for delayed wound healing. Though in young healthy patients such donor sites have minimal risk, patients with risk factors for delayed wound healing are more challenging. We present a method for graft donor site management that offers an alternative to healing by secondary intention for patients with higher risk of poor wound healing. In those patients considered to be at high risk for donor site healing complications, we chose to treat the donor site with a split-thickness skin graft, or "graft back" procedure. An additional graft is taken adjacent to the initial donor site, and meshed 4:1 to cover both donor sites at once. Out of the 17 patients who received this procedure, 1 patient had a complication from the procedure that did not require an operation, and all patients appear to have good functional and cosmetic outcomes. No patients had any graft loss or graft infection. Histologic analysis showed complete epithelialization of the back-grafted area. The graft back method converts an open wound to a covered wound and may result in decreased wound healing time, improved cosmetic outcomes, and fewer complications, particularly in patients where wound healing is a concern. Importantly, it seems to have minimal morbidity. More detailed prospective studies are needed to ensure no additional risk is incurred by this procedure. PMID- 27003742 TI - Refining mimicry: phenotypic variation tracks the local optimum. AB - Mullerian mimicry between chemically defended preys is a textbook example of natural selection favouring phenotypic convergence onto a shared warning signal. Studies of mimicry have concentrated on deciphering the ecological and genetic underpinnings of dramatic switches in mimicry association, producing a well-known mosaic distribution of mimicry patterns across geography. However, little is known about the accuracy of resemblance between natural comimics when the local phenotypic optimum varies. In this study, using analyses of wing shape, pattern and hue, we quantify multimodal phenotypic similarity between butterfly comimics sharing the so-called postman pattern in different localities with varying species composition. We show that subtle but consistent variation between populations of the localized species, Heliconius timareta thelxinoe, enhance resemblance to the abundant comimics which drive the mimicry in each locality. Those results suggest that rarer comimics track the changes in the phenotypic optimum caused by gradual changes in the composition of the mimicry community, providing insights into the process by which intraspecific diversity of mimetic pattern may arise. Furthermore, our results suggest a multimodal evolution of similarity, with coordinated convergence in different features of the phenotype such as wing outline, pattern and hue. Finally, multilocus genotyping allows estimating local hybridization rates between H. timareta and comimic H. melpomene in different populations, raising the hypothesis that mimicry refinement between closely related comimics may be enhanced by adaptive introgression at loci modifying the accuracy of resemblance. PMID- 27003743 TI - Hepatic gateways. AB - The intestinal mucosal barrier contributes to homeostasis by limiting systemic dissemination of microbes and toxins while allowing nutrients to pass through to the systemic circulation. In a recent issue of Science, Spadoni et al. demonstrated a novel mechanism to enable this selectivity: the existence of a gut vascular barrier (GVB) as indicated by a series of studies on the interaction between murine and human intestine with Salmonella typhimurium species . They showed that (i) enteroglial cells and pericytes in contact with endothelial cells (ECs) form the GVB (ii) Salmonella typhimurium can penetrate it by a mechanism dependent on the pathogenicity island (Spi) 2-encoded type III secretion system and on decreased beta-catenin dependent signaling in gut endothelial cells. Understanding the GVB may provide new insights into the regulation of the gut liver axis. PMID- 27003744 TI - Response to I. Batinic-Haberle et al. PMID- 27003746 TI - Shock and awe: Distinct effects of taboo words on lexical decision and free recall. AB - Taboo stimuli are highly arousing, but it has been suggested that they also have inherent taboo-specific properties such as tabooness, offensiveness, or shock value. Prior studies have shown that taboo words have slower response times in lexical decision and higher recall probabilities in free recall; however, taboo words often differ from other words on more than just arousal and taboo properties. Here, we replicated both of these findings and conducted detailed item analyses to determine which word properties drive these behavioural effects. We found that lexical-decision performance was best explained by measures of lexical accessibility (e.g., word frequency) and tabooness, rather than arousal, valence, or offensiveness. However, free-recall performance was primarily driven by emotional word properties, and tabooness was the most important emotional word property for model fit. Our results suggest that the processing of taboo words is influenced by distinct sets of factors and by an intrinsic taboo-specific property. PMID- 27003747 TI - Age-related changes in photosensitive melanopsin-expressing retinal ganglion cells correlate with circadian rhythm impairments in sighted and blind rats. AB - The melanopsin system consists of intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (mRGCs). These mRGCs mediate several non-image-forming visual functions, including light entrainment of circadian rhythms. Here we evaluate age-related alterations of the melanopsin system and circadian rhythms in P23H line 1 (P23H-1) rats, a rodent model of retinitis pigmentosa (RP). In homozygous P23H-1 rats and wild-type control rats from the same genetic background (Sprague-Dawley), body temperature and locomotor activity were continuously monitored at 10-min intervals for 7 days, once every 4-5 weeks, between 2 and 24 months of age, using a telemetry transmitter. The distribution and number of mRGCs were assessed in control rats at 12, 18, and 24 months of age and in P23H-1 rats aged 12, 18, 24, and 30 months by immunostaining whole-mount retinas with antibodies against melanopsin. The mean density of mRGCs in control rats showed no significant variations when evaluated at 12 and 18 months of age, and fell by approximately 56% between 18 and 24 months of age. Meanwhile, a significant decrease in the mean number of mRGCs was found in 18-month-old P23H-1 rats as compared to 18-month-old control rats (81% decrease). Parametric and non parametric analyses of the records showed a gradual age-dependent weakening of body temperature and locomotor activity circadian rhythms robustness in both control and P23H-1 rats from 2 to 24 months of age. However, body temperature and locomotor activity circadian patterns were less robust throughout the experiment in P23H-1 as compared to control rats, with lower amplitude, weaker coupling strength to environmental zeitgebers and higher fragmentation of the rhythms. The present study shows that the degeneration of photoreceptors and inner retinal neurons, characteristic of RP, has age-related degenerative effects on the melanopsin system and is associated with weaker circadian patterns. PMID- 27003748 TI - Isotope Effects in the Resonant Inelastic Soft X-ray Scattering Maps of Gas-Phase Methanol. AB - The electronic structure of gas-phase methanol molecules (H3COH, H3COD, and D3COD) at atmospheric pressure was investigated using resonant inelastic soft X ray scattering (RIXS) at the O K and C K edges. We observe strong changes of the relative emission intensities of all valence orbitals as a function of excitation energy, which can be related to the symmetries of the involved orbitals causing an angularly anisotropic RIXS intensity. Furthermore, all observed emission lines are subject to strong spectator shifts of up to -0.9 eV at the O K edge and up to -0.3 eV at the C K edge. At the lowest O K resonance, we find clear evidence for dissociation of the methanol molecule on the time scale of the RIXS process, which is illustrated by comparing X-ray emission spectra of regular and deuterated methanol. PMID- 27003750 TI - Interview with Inder Verma, PhD. PMID- 27003751 TI - Dystrophin Gene Replacement and Gene Repair Therapy for Duchenne Muscular Dystrophy in 2016: An Interview. AB - After years of relentless efforts, gene therapy has now begun to deliver its therapeutic promise in several diseases. A number of gene therapy products have received regulatory approval in Europe and Asia. Duchenne muscular dystrophy (DMD) is an X-linked inherited lethal muscle disease. It is caused by mutations in the dystrophin gene. Replacing and/or repairing the mutated dystrophin gene holds great promises to treated DMD at the genetic level. Last several years have evidenced significant developments in preclinical experimentations in murine and canine models of DMD. There has been a strong interest in moving these promising findings to clinical trials. In light of rapid progress in this field, the Parent Project Muscular Dystrophy (PPMD) recently interviewed me on the current status of DMD gene therapy and readiness for clinical trials. Here I summarized the interview with PPMD. PMID- 27003752 TI - Safety and Biodistribution Evaluation in CNGB3-Deficient Mice of rAAV2tYF-PR1.7 hCNGB3, a Recombinant AAV Vector for Treatment of Achromatopsia. AB - Applied Genetic Technologies Corporation (AGTC) is developing rAAV2tYF-PR1.7 hCNGB3, a recombinant adeno-associated virus (rAAV) vector expressing the human CNGB3 gene, for treatment of achromatopsia, an inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. We report here results of a study evaluating safety and biodistribution of rAAV2tYF-PR1.7-hCNGB3 in CNGB3-deficient mice. Three groups of animals (n = 35 males and 35 females per group) received a subretinal injection in one eye of 1 MUl containing either vehicle or rAAV2tYF PR1.7-hCNGB3 at one of two dose concentrations (1 * 10(12) or 4.2 * 10(12) vg/ml) and were euthanized 4 or 13 weeks later. There were no test-article-related changes in clinical observations, body weights, food consumption, ocular examinations, clinical pathology parameters, organ weights, or macroscopic observations at necropsy. Cone-mediated electroretinography (ERG) responses were detected after vector administration in the treated eyes in 90% of animals in the higher dose group and 31% of animals in the lower dose group. Rod-mediated ERG responses were reduced in the treated eye for all groups, with the greatest reduction in males given the higher dose of vector, but returned to normal by the end of the study. Microscopic pathology results demonstrated minimal mononuclear cell infiltrates in the retina and vitreous of some animals at the interim euthanasia and in the vitreous of some animals at the terminal euthanasia. Serum anti-AAV antibodies developed in most vector-injected animals. No animals developed antibodies to hCNGB3. Biodistribution studies demonstrated high levels of vector DNA in vector-injected eyes but little or no vector DNA in nonocular tissue. These results support the use of rAAV2tYF-PR1.7-hCNGB3 in clinical studies in patients with achromatopsia caused by CNGB3 mutations. PMID- 27003754 TI - Electrodeposition of High Density Silver Nanosheets with Controllable Morphologies Served as Effective and Reproducible SERS Substrates. AB - Silver nanosheets with a nanogap smaller than 10 nm and high reproducibility were constructed through simple and environmentally friendly electrodeposition method on copper plate. The sizes of the nanogaps can be varied from around 7 to 150 nm by adjusting the deposition time and current density. The nanosheets with different nanogaps exhibited varied surface-enhanced Raman scattering (SERS) properties due to electromagnetic mechanism (EM). The optimized high density silver nanosheets with a nanogap smaller than 10 nm showed effective SERS ability with an enhanced factor as high as 2.0 * 10(5). Furthermore, the formation mechanism of the nanosheets during the electrodeposition process has been investigated by discussing the influence of boric acid and current density. This method has proved to be applicable on different metal substrates, which exhibits the potential to be widely used in different fields. PMID- 27003753 TI - Safety and Biodistribution Evaluation in Cynomolgus Macaques of rAAV2tYF-PR1.7 hCNGB3, a Recombinant AAV Vector for Treatment of Achromatopsia. AB - Applied Genetic Technologies Corporation (AGTC) is developing rAAV2tYF-PR1.7 hCNGB3, a recombinant adeno-associated viral (rAAV) vector expressing the human CNGB3 gene, for treatment of achromatopsia, an inherited retinal disorder characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. We report here results of a study evaluating the safety and biodistribution of rAAV2tYF-PR1.7-hCNGB3 in cynomolgus macaques. Three groups of animals (n = 2 males and 2 females per group) received a subretinal injection in one eye of 300 MUl containing either vehicle or rAAV2tYF-PR1.7 hCNGB3 at one of two concentrations (4 * 10(11) or 4 * 10(12) vector genomes/ml) and were evaluated over a 3-month period before being euthanized. Administration of rAAV2tYF-PR1.7-hCNGB3 was associated with a dose-related anterior and posterior segment inflammatory response that was greater than that observed in eyes injected with the vehicle control. Most manifestations of inflammation improved over time except that vitreous cells persisted in vector-treated eyes until the end of the study. One animal in the lower vector dose group was euthanized on study day 5, based on a clinical diagnosis of endophthalmitis. There were no test article-related effects on intraocular pressure, visual evoked potential responses, hematology or clinical chemistry parameters, or gross necropsy observations. Histopathological examination demonstrated minimal mononuclear infiltrates in all vector-injected eyes. Serum anti-AAV antibodies developed in all vector-injected animals. No animals developed antibodies to CNGB3. Biodistribution studies demonstrated high levels of vector DNA in the injected eye but minimal or no vector DNA in any other tissue. These results support the use of rAAV2tYF-PR1.7-hCNGB3 in clinical studies in patients with achromatopsia caused by CNGB3 mutations. PMID- 27003756 TI - A Traceless Selection: Counter-selection System That Allows Efficient Generation of Transposon and CRISPR-modified T-cell Products. AB - Recent years have seen major breakthroughs in genome-engineering systems, such as transposon-mediated gene delivery systems and CRISPR-Cas9-mediated genome-editing tools. In these systems, transient expression of auxiliary genes is responsible for permanent genomic modification. For both systems, it would be valuable to select for cells that are likely to undergo stable genome modification. Importantly, in particular for clinical applications of genome-engineered cell products, it will also be of importance to remove those cells that, due to random vector integration, display an unwanted stable expression of the auxiliary gene. Here, we develop a traceless selection system that on the one hand allows efficient enrichment of modified cells, and on the other hand can be used to select against cells that retain expression of the auxiliary gene. The value of this system to produce highly enriched-auxiliary gene-free cell products is demonstrated. PMID- 27003755 TI - Design, Characterization, and Lead Selection of Therapeutic miRNAs Targeting Huntingtin for Development of Gene Therapy for Huntington's Disease. AB - Huntington's disease (HD) is a neurodegenerative disorder caused by accumulation of CAG expansions in the huntingtin (HTT) gene. Hence, decreasing the expression of mutated HTT (mtHTT) is the most upstream approach for treatment of HD. We have developed HTT gene-silencing approaches based on expression cassette-optimized artificial miRNAs (miHTTs). In the first approach, total silencing of wild-type and mtHTT was achieved by targeting exon 1. In the second approach, allele specific silencing was induced by targeting the heterozygous single-nucleotide polymorphism (SNP) rs362331 in exon 50 or rs362307 in exon 67 linked to mtHTT. The miHTT expression cassette was optimized by embedding anti-HTT target sequences in ten pri-miRNA scaffolds and their HTT knockdown efficacy, allele selectivity, passenger strand activity, and processing patterns were analyzed in vitro. Furthermore, three scaffolds expressing miH12 targeting exon 1 were incorporated in an adeno-associated viral serotype 5 (AAV5) vector and their HTT knock-down efficiency and pre-miHTT processing were compared in the humanized transgenic Hu128/21 HD mouse model. Our data demonstrate strong allele-selective silencing of mtHTT by miSNP50 targeting rs362331 and total HTT silencing by miH12 both in vitro and in vivo. Ultimately, we show that HTT knock-down efficiency and guide strand processing can be enhanced by using different cellular pri-miRNA scaffolds. PMID- 27003757 TI - In Vivo siRNA Delivery Using JC Virus-like Particles Decreases the Expression of RANKL in Rats. AB - Bone remodeling requires a precise balance between formation and resorption. This complex process involves numerous factors that orchestrate a multitude of biochemical events. Among these factors are hormones, growth factors, vitamins, cytokines, and, most notably, osteoprotegerin (OPG) and the receptor activator for nuclear factor-kappaB ligand (RANKL). Inflammatory cytokines play a major role in shifting the RANKL/OPG balance toward excessive RANKL, resulting in osteoclastogenesis, which in turn initiates bone resorption, which is frequently associated with osteoporosis. Rebalancing RANKL/OPG levels may be achieved through either upregulation of OPG or through transient silencing of RANKL by means of RNA interference. Here, we describe the utilization of a viral capsid based delivery system for in vivo and in vitro RNAi using synthetic small interfering RNA (siRNA) molecules in rat osteoblasts. Polyoma JC virus-derived virus-like particles are capable of delivering siRNAs to target RANKL in osteoblast cells both in vitro and in a rat in vivo system. Expression levels were monitored using quantitative real-time polymerase reaction and enzyme-linked immunosorbent assay after single and repeated injections over a 14-day period. Our data indicate that this is an efficient and safe route for in vivo delivery of gene modulatory tools to study important molecular factors in a rat osteoporosis model. PMID- 27003758 TI - A Small Indel Mutant Mouse Model of Epidermolytic Palmoplantar Keratoderma and Its Application to Mutant-specific shRNA Therapy. AB - Epidermolytic palmoplantar keratoderma (EPPK) is a relatively common autosomal dominant skin disorder caused by mutations in the keratin 9 gene (KRT9), with few therapeutic options for the affected so far. Here, we report a knock-in transgenic mouse model that carried a small insertion-deletion (indel) mutant of Krt9, c.434delAinsGGCT (p.Tyr144delinsTrpLeu), corresponding to the human mutation KRT9/c.500delAinsGGCT (p.Tyr167delinsTrpLeu), which resulted in a human EPPK-like phenotype in the weight-stress areas of the fore- and hind-paws of both Krt9(+/mut) and Krt9(mut/mut) mice. The phenotype confirmed that EPPK is a dominant-negative condition, such that mice heterozygotic for the K9-mutant allele (Krt9(+/mut)) showed a clear EPPK-like phenotype. Then, we developed a mutant-specific short hairpin RNA (shRNA) therapy for EPPK mice. Mutant-specific shRNAs were systematically identified in vitro using a luciferase reporter gene assay and delivered into Krt9(+/mut) mice. shRNA-mediated knockdown of mutant protein resulted in almost normal morphology and functions of the skin, whereas the same shRNA had a negligible effect in wild-type K9 mice. Our results suggest that EPPK can be treated by gene therapy, and this has significant implications for future clinical application. PMID- 27003760 TI - The Effects of the Organic-Inorganic Interactions on the Thermal Transport Properties of CH3NH3PbI3. AB - Methylammonium lead iodide perovskite (CH3NH3PbI3), the most investigated hybrid organic-inorganic halide perovskite, is characterized by a quite low thermal conductivity. The rotational motion of methylammonium cations is considered responsible for phonon transport suppression; however, to date, the specific mechanism of the process has not been clarified. In this study, we elucidate the role of rotations in thermal properties based on molecular dynamics simulations. To do it, we developed an empirical potential for CH3NH3PbI3 by fitting to ab initio calculations and evaluated its thermal conductivity by means of nonequilibrium molecular dynamics. Results are compared with model systems that include different embedded cations, and this comparison shows a dominant suppression effect provided by rotational motions. We also checked the temperature dependence of the vibrational density of states and specified the energy range in which anharmonic couplings occur. By means of phonon dispersion analysis, we were able to fully elucidate the suppression mechanism: the rotations are coupled with translational motions of cations, via which inorganic lattice vibrations are coupled and scatter each other. PMID- 27003759 TI - Defining Optimal Head-Tilt Position of Resuscitation in Neonates and Young Infants Using Magnetic Resonance Imaging Data. AB - Head-tilt maneuver assists with achieving airway patency during resuscitation. However, the relationship between angle of head-tilt and airway patency has not been defined. Our objective was to define an optimal head-tilt position for airway patency in neonates (age: 0-28 days) and young infants (age: 29 days-4 months). We performed a retrospective study of head and neck magnetic resonance imaging (MRI) of neonates and infants to define the angle of head-tilt for airway patency. We excluded those with an artificial airway or an airway malformation. We defined head-tilt angle a priori as the angle between occipito-ophisthion line and ophisthion-C7 spinous process line on the sagittal MR images. We evaluated medical records for Hypoxic Ischemic Encephalopathy (HIE) and exposure to sedation during MRI. We analyzed MRI of head and neck regions of 63 children (53 neonates and 10 young infants). Of these 63 children, 17 had evidence of airway obstruction and 46 had a patent airway on MRI. Also, 16/63 had underlying HIE and 47/63 newborn infants had exposure to sedative medications during MRI. In spontaneously breathing and neurologically depressed newborn infants, the head tilt angle (median +/- SD) associated with patent airway (125.3 degrees +/- 11.9 degrees ) was significantly different from that of blocked airway (108.2 degrees +/- 17.1 degrees ) (Mann Whitney U-test, p = 0.0045). The logistic regression analysis showed that the proportion of patent airways progressively increased with an increasing head-tilt angle, with > 95% probability of a patent airway at head-tilt angle 144-150 degrees . PMID- 27003762 TI - Comparative cardiovascular safety of glucagon-like peptide-1 receptor agonists versus other antidiabetic drugs in routine care: a cohort study. AB - AIMS: To evaluate the comparative cardiovascular disease (CVD) safety of glucagon like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM). METHODS: Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score matched cohorts of patients with T2DM aged >=18 years treated with metformin who initiated a GLP-1 RA or a comparator, i.e. DPP-4 inhibitor (n = 35 534), second generation sulphonylureas (n = 28 138) or insulin (n = 47 068), between 2005 and 2013. We examined the association between drug initiation and a composite CVD endpoint, comprising hospitalizations for acute myocardial infarction, unstable angina, stroke or coronary revascularization. RESULTS: During the course of 1 year, there were 13.9 and 13.7 CVD events per 1000 person-years among propensity score-matched initiators of GLP-1 RAs versus DPP-4 inhibitors [hazard ratio (HR) 1.02; 95% confidence interval (CI) 0.84-1.24]; and 12.1 versus 14.0 events among initiators of GLP-1 RAs versus sulphonylureas (HR 0.86; 95% CI 0.69-1.08). The effect estimates for GLP-1 RAs versus insulin were sensitive to the adjustment for glycated haemoglobin, after which the HR was 1.01 (95% CI 0.73-1.41). Results were robust across several sensitivity analyses, including an as-treated analysis considering up to 8.7 years of follow-up. CONCLUSIONS: This large study, performing head-to-head comparisons of GLP-1 RAs with other antidiabetic agents in real-world patients, provides estimates of relative safety precise enough to exclude large differences in CVD risk and adds further understanding to results from recent clinical trials. PMID- 27003761 TI - Discovery of Entrectinib: A New 3-Aminoindazole As a Potent Anaplastic Lymphoma Kinase (ALK), c-ros Oncogene 1 Kinase (ROS1), and Pan-Tropomyosin Receptor Kinases (Pan-TRKs) inhibitor. AB - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase responsible for the development of different tumor types. Despite the remarkable clinical activity of crizotinib (Xalkori), the first ALK inhibitor approved in 2011, the emergence of resistance mutations and of brain metastases frequently causes relapse in patients. Within our ALK drug discovery program, we identified compound 1, a novel 3-aminoindazole active on ALK in biochemical and in cellular assays. Its optimization led to compound 2 (entrectinib), a potent orally available ALK inhibitor active on ALK-dependent cell lines, efficiently penetrant the blood-brain barrier (BBB) in different animal species and highly efficacious in in vivo xenograft models. Moreover, entrectinib resulted to be strictly potent on the closely related tyrosine kinases ROS1 and TRKs recently found constitutively activated in several tumor types. Entrectinib is currently undergoing phase I/II clinical trial for the treatment of patients affected by ALK-, ROS1-, and TRK-positive tumors. PMID- 27003763 TI - Efficacy of L-arginine for preventing preeclampsia in high-risk pregnancies: A double-blind, randomized, clinical trial. AB - OBJECTIVE: This study aimed to estimate the effectiveness of L-arginine for preventing preeclampsia in high-risk pregnancy. METHODS: We performed a randomized, double-blind, placebo-controlled, clinical trial in patients with high-risk factors for preeclampsia. Fifty subjects received L-arginine, beginning from the 20th week of gestation. An additional 50 patients received homologated placebo. RESULTS: The placebo group had a higher number of cases of preeclampsia (11/47) compared with the L-arginine group (3/49, P = 0.01). Birth weight was higher in the L-arginine group and there was a smaller number of preterm births (P = 0.03). CONCLUSION: L-arginine is effective for preventing preeclampsia. PMID- 27003764 TI - Hypoxia in breast cancer. AB - Breast cancer continues to be one of the most common malignancies and is a serious problem particularly in women, although men may also be affected. Such lesions are commonly accompanied by hypoxia, and therefore hypoxia-dependent mechanisms, such as overexpression of hypoxia-inducible factor (HIF), the mechanisms are studied as part of the search for a novel method of cancer treatment. Blocking the activity of HIF and HIF-dependent molecular changes raises hopes for identification of a molecular target to inhibit the tumor growth or even to completely prevent its progression. However, this is difficult due to the crucial role HIF plays in numerous processes occurring not only in cancer cells but mostly in healthy systemic cells in physiological conditions. PMID- 27003765 TI - Androgen receptor in male breast cancer. AB - We present the androgen receptor (AR) status in 32 breast cancers diagnosed in male patients. Androgen receptor expression was found in 62.5% tumors and it was more frequent (85% of cases) in estrogen-positive tumours. The analyses of its impact on treatment results showed that AR immmunopositivity is a prognostic factor for overall survival, and AR immunonegativity is also correlated with worse prognosis (distant metastases developed more frequently and earlier). PMID- 27003766 TI - Clinicopathologic analysis of isolated hematuria in child/adolescent and adult patients. AB - To our knowledge, no in-depth clinicopathologic study of isolated hematuria (IH) is currently available. To address this gap, we analyzed the clinicopathologic features of IH as it manifests in child/adolescent and adult patients. The clinical data and pathological types of 543 IH patients who underwent renal pathological examinations from January 2005 to June 2010 were retrospectively analyzed. Clinical manifestations differed among the age groups: children/adolescents exhibited the highest percentage of mesangial proliferative glomerulonephritis (41.78%), whereas adults showed the highest percentage of immunoglobulin A nephropathy (IgAN) (52.39%). In addition, the percentage of IH patients who were classified according to clinical pathology differed from that of patients who were classified according to renal pathological type. Patients with IgAN who were found to have minimal proteinuria had more severe IH. For IH patients, especially those with a small amount of proteinuria, renal biopsy should be performed as early as possible in order to develop a long-term treatment plan and prognosis evaluation. PMID- 27003767 TI - Spectrum of biopsy-proven renal diseases in patients with type 2 diabetes mellitus. A single center study. AB - This is the first report from Poland documenting biopsy-proven renal diseases in type 2 diabetes mellitus. We analyzed the data of 76 patients with type 2 diabetes who underwent renal biopsy and were diagnosed in the Department of Nephropathology, Medical University of Lodz. The patients were divided into the following three groups according to the histological diagnosis: group I - isolated non-diabetic renal disease (NDRD); group II - NDRD superimposed on underlying diabetic nephropathy (NDRD + DN); and group III - isolated diabetic nephropathy (DN). Non-diabetic renal disease was found in 38 patients (50%), non diabetic renal disease superimposed on underlying diabetic nephropathy was diagnosed in 11 patients (14.5%), and isolated diabetic nephropathy was seen in 27 patients (35.5%). The most common glomerular lesion found in groups I and II was focal segmental glomerulosclerosis (FSGS). On the basis of clinical and laboratory parameters, differentiating NDRD from DN in diabetic patients is not always obvious. However, our study revealed that hematuria, short duration of diabetes and the absence of diabetic retinopathy in type 2 diabetic patients manifesting renal involvement may suggest NDRD. The only way to distinguish NDRD from DN is histological evaluation of renal tissue. PMID- 27003768 TI - Determinants of liver disease progression in children with chronic hepatitis C virus infection. AB - Histopathological features and determinants of liver disease progression were analyzed in 42 treatment-naive children (mean age: 10.7 +/-3.7) with chronic hepatitis C (14/42 infected vertically and 26/42 horizontally). Histopathological evaluation was performed according to Knodell's modified system. Predictors of necroinflammation and fibrosis were identified using linear regression analyses. Most children presented with mild necroinflammation and fibrosis (mean grade 4.3 +/-2.7, mean staging 1.2 +/-0.8), irrespective of the mode of transmission. Vertically infected children were younger than those infected horizontally (8.6 +/-2.5 vs. 11.5 +/-3.7 years, p = 0.02). Alanine and aspartate aminotransferase (ALT and AST) levels were associated with necroinflammation (p = 0.003 and p = 0.01 for ALT and AST, respectively) and fibrosis (p = 0.01 and p = 0.04, respectively). Other positive independent predictors of fibrosis included duration of infection (p = 0.03) and body mass index (BMI) z-score (p = 0.03). Children with chronic hepatitis C presented with mild liver changes over a decade after the infection, irrespective of the mode of transmission. Since fibrosis is a time-dependent process, progression of the liver disease in vertically infected children may occur at a younger age compared to patients infected horizontally. Aminotransferase levels were associated with necroinflammation and fibrosis. Longer duration of infection and a higher BMI z-score were associated with more severe fibrosis. PMID- 27003769 TI - The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor beta and interferon gamma in metastatic lymph nodes in malignant melanoma. AB - We analyzed the prognostic significance of indoleamine-2,3-dioxygenase (IDO) and type 1 receptors for transforming growth factor beta (TGF-betaR1) and interferon gamma (IFN-gammaR1) in resected nodal metastases of 48 malignant melanoma patients. In 32 cases the corresponding skin tumors were available. We used immunohistochemical (IHC) staining which was assessed by pathologists and by a computer-aided algorithm that yielded quantitative results, both absolute and relative. We correlated the results with the patient outcome. We identified absolute computer-assessed IDO levels as positively correlated with increased risk of death in a multivariate model (HR = 1.02; 95% CI: 1.002-1.04; p = 0.03). In univariate analysis, patients with IDO levels below the median had a better overall survival time (30.3 vs. 17.5 months; p = 0.03). TGF-betaR1 and IFN gammaR1 expression was modestly correlated (R = 0.34; p lt; 0.05) and TGF-betaR1 expression was lower in lymph nodes than in matched primary skin tumors (Z = 2.87; p = 0.004). The pathologists' and computer-aided IHC assessment demonstrated high correlation levels (R = 0.61, R = 0.74 and R = 0.88 for IDO, TGF-betaR1 and IFN-gammaR1, respectively). Indoleamine-2,3-dioxygenase is prognostic for the patient outcome in melanoma with nodal involvement and should be investigated prospectively for its predictive significance. IHC assessment by computer-aided methods is recommended as its gives IHC more objectivity and reproducibility. ecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together. PMID- 27003770 TI - Rhabdomyosarcoma in children in the light of isotope ratio mass spectrometry. AB - Rhabdomyosarcoma is the third most common solid tumor in children and the most common soft tissue sarcoma in this age group. However, 5-year survival is only observed in approximately 70% of cases, and the prognosis for patients with progressive disease is still poor. The authors hypothesize that the still unidentified differences in embryonal and alveolar tumor biology reflect the complex chemical reactions occurring during cell growth and metabolism and may be pursued in isotopic fractionation processes. Presented herein is the first evaluation of the nitrogen and carbon isotope ratio using isotope ratio mass spectrometry in the two major rhabdomyosarcoma histologic types. 15N enrichment was found in tumor tissues of embryonal histological type. The obtained result may indicate that individual patient considerations such as isotope ratio, in addition to widely accepted prognostic factors, may facilitate patient classification in terms of risk groups. PMID- 27003771 TI - Prognostic value of p53 protein expression in giant cell tumor of bone. AB - Giant cell tumor of bone (GCTB) is a benign tumor with a tendency for local recurrence. GCTB may cause lung metastases, and secondary malignant GCTB is rare. Its histological appearance does not predict local aggressiveness and/or the metastatic potential of the tumor. We aimed to investigate the prognostic value of the Ki-67 proliferative index and p53 protein expression in GCTB in predicting local recurrence, lung metastasis, and malignant transformation. We retrospectively reviewed 42 cases of GCTB. The p53 expression was positive in 20 cases. We used 10% as a cut-off value for p53 expression. In 10 cases, there were local recurrences. Lung metastases were found in three cases and malignant transformation was found in one case with classical GCTB located in the sacrum three years following diagnosis. The Ki-67 index was higher in cases with recurrence, but this difference was not statistically significant. Of the recurrent cases, two had no p53 staining while eight had moderate-to-strong staining. The staining was usually weakly positive in the non-recurrent cases. In conclusion, we believe that p53 may be used as a marker for the biological behavior of GCTB. PMID- 27003772 TI - Mast cells in systemic and cutaneous lupus erythematosus. AB - Mast cells (MCs) are known to be regulators of inflammation and immunity, due to the released mediators and expressed cell surface molecules. Lupus erythematosus (LE) is a group of diseases which can be systemic or limited to the skin. Due to the fact that cytokines and chemokines produced by inflammatory cells contribute to the pathogenesis of LE, we quantified the number of mast cells present in the skin. The aim of the study was to compare the chymase-positive and tryptase positive mast cell counts within skin biopsies from patients with systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). The material consisted of 45 skin biopsies: 6 with SLE, 34 with DLE and 5 with SCLE. Chymase- and tryptase-positive cells were stained by immunohistochemistry and counted. The mean count of chymase-positive mast cells was 85.14 hpf for the whole group, 35.83 for SLE, 88.48 for DLE and 121.6 for SCLE. The mean count of tryptase-positive cells was 120.05 hpf for the entire group, 59.17 for SLE, 126.42 for DLE and 149.8 for SCLE. The differences between groups were significant for chymase- and tryptase-positive cells. PMID- 27003773 TI - Research on genesis of adipocytic metaplasia in uterine fibroids. AB - The genesis of lipoleiomyoma has not been explained yet. Immunohistochemical examinations were performed on 17 lipoleiomyomas in women aged 43-82 (mean age: 51 +/-9 years). Four types of myomas were distinguished: 1) pure leiomyoma, 2) fibroleiomyoma, 3) hyalinizing leiomyoma, 4) strongly hyalinized myoma, along with three degrees of progression of adipocytic metaplasia: 1) up to 25% of lipocytes, 2) up to 50% of lipocytes, and 3) over 50% of lipocytes in the analyzed sample, along with three degrees of progression of adipocytic metaplasia: 1) up to 25% of lipocytes, 2) up to 50% of lipocytes, and 3) over 50% of lipocytes in the analyzed sample. A positive correlation was found between the age of women and rate of development of metaplasia (r = 0.51, p = 0.035) as well as with activity of the estrogen receptor in the primary tumor (r = 0.53, p = 0.03). New mucous perivascular tissue was reported among 11.8% of patients and on this basis lipocytes were formed. The appearance of subendothelial granular cells of large blood vessels with a positive reaction for smooth muscle actin (SMA) and CD68 was reported in 17.7%. Results of immunohistochemical research seem to confirm that lipocytes de novo come from the primal pluripotent cells of the tumor stroma and not from the fatty degeneration of myocytes. PMID- 27003774 TI - Morphometric differentiation of squamous cell carcinoma and adenocarcinoma of the cervix. AB - The aim of the study was to define the morphometric characteristics of squamous cell carcinoma (SCC) and adenocarcinoma (AC) cells and identify opportunities to differentiate these tumors based on determination of the morphometric characteristics in order to use the results of research in the diagnosis of cervical cancer. Pap smears with two histopathologically confirmed cervix cancers were used for testing. For the morphometric assessment of cancer cells the dotSlide program was used. The mean nucleus area for AC cells was 126.62 * 10(-6) m(2), while this value for SCC was 145.07 * 10(-6) m(2) (p = 0.000132). The mean circumference of AC cells was 42.43 * 10(-6) m, while for SCC cells it was 46.67 * 10(-6) m (p = 0.00). AC cell diameter was 13.83 um, whereas for SCC cells it was 15.36 * 10(-6) m. On average the AC cell surface area was 195.72 * 10(-6) m(2), while for SCC cells it was 249.94 * 10(-6) m(2) (p = 0.00565). The mean AC cell circumference was 54.90 MUm, whereas for SCC cells it was 65.23 * 10(-6) m (p = 0.00607). The research shows that, despite the presence of statistically significant differences for each morphometric parameter, determination of cancer type cannot be used in the diagnosis. PMID- 27003775 TI - Expression of beta-catenin and its correlation with metastatic progression of esophagogastric junction adenocarcinoma. AB - The evaluation of beta-catenin expression in adenocarcinoma of the esophagogastric junction and its influence on cancer progression. Sixty-one patients who were diagnosed with adenocarcinoma of the esophagogastric junction were examined. We evaluated beta-catenin distribution in the cell membrane and the cell nucleus in adenocarcinoma of the esophagogastric junction type 1 and type 3. Our findings showed lack of a statistically significant difference in evaluation of adenocarcinoma type 1 and type 3 aggressiveness. However, we found a statistically significant association with the T and N stage, although we did not find an effect of them on patient survival. Patients with cellular membrane and cell nucleus staining comprise a group of patients with higher risk of malignancy progression in adenocarcinoma of the esophagogastric junction types 1 and 3. PMID- 27003776 TI - Histopathological assessment of residual retroperitoneal mass removed in patients after chemotherapy for non-seminomatous germ cell tumours of the testis. AB - Between 1990 and 1999, 182 men were treated for non-seminomatous germ cell testicular tumours. In 24 of them after chemotherapy a residual retroperitoneal mass was removed. In 14 of them additional immunohistochemical (IHC) examinations using antibodies against cytokeratins, vimentin, PLAP, CD30, AFP, betahCG, p53, and MIB-1 were performed. We compared the results of those additional studies with the results of routine histopathological examination. Histological assessment revealed most frequently (ca. 54% of cases) non-neoplastic lesions, i.e. fibro-cystic, necrotic or inflammatory tumours and lymphatic tissue. In about 33% of cases, surviving live neoplastic cells were found. PMID- 27003777 TI - Asymptomatic gastric heterotopia in the rectum with Helicobacter pylori infection. AB - Gastric heterotopia is very rare in the rectum - less than 50 cases have been reported so far. Only in six of them Helicobacter pylori has been observed in heterotopic mucosa. We report a case of a 58-year-old woman with asymptomatic gastric heterotopia in the rectum, incidentally revealed during colonoscopy as a small, sessile polyp. The presence of H. pylori was confirmed by immunohistochemistry. This finding supports the opinion that H. pylori may pass along the gastrointestinal tract in a viable form and that the fecal-oral route of transmission is possible. PMID- 27003778 TI - High-risk follicular dendritic cell sarcoma of the tonsil mimicking nasopharyngeal carcinoma. AB - Follicular dendritic cell sarcoma (FDCS) is often misdiagnosed as a carcinoma or malignant lymphoma due to morphological variability. In FDCS application of routine antibody panels without CD21 and CD23 increases the misdiagnosis rate, because the tumor cells often show focal positivity for usual immunohistochemical markers. Our new case showed a distinct picture due to the uncommon tumor architecture, with extensive areas of necrosis and hemorrhage, the presence of nuclear atypia, and an increased mitotic count and Ki-67 index. These features suggest the classification of this tumor in the category of high-risk malignancies, with uncommon features of FDCSs. PMID- 27003779 TI - A Viewpoint on Wearable Technology-Enabled Measurement of Wellbeing and Health Related Quality of Life in Parkinson's Disease. AB - In this viewpoint, we discuss how several aspects of Parkinson's disease (PD) - known to be correlated with wellbeing and health-related quality of life-could be measured using wearable devices ('wearables'). Moreover, three people with PD (PwP) having exhaustive experience with using such devices write about their personal understanding of wellbeing and health-related quality of life, building a bridge between the true needs defined by PwP and the available methods of data collection. Rapidly evolving new technologies develop wearables that probe function and behaviour in domestic environments of people with chronic conditions such as PD and have the potential to serve their needs. Gathered data can serve to inform patient-driven management changes, enabling greater control by PwP and enhancing likelihood of improvements in wellbeing and health-related quality of life. Data can also be used to quantify wellbeing and health-related quality of life. Additionally these techniques can uncover novel more sensitive and more ecologically valid disease-related endpoints. Active involvement of PwP in data collection and interpretation stands to provide personally and clinically meaningful endpoints and milestones to inform advances in research and relevance of translational efforts in PD. PMID- 27003780 TI - Variation in Recent Onset Parkinson's Disease: Implications for Prodromal Detection. AB - BACKGROUND: The detection of prodromal Parkinson's disease (PD) is desirable to test drugs with neuroprotective potential, but will be affected by known disease variations. OBJECTIVE: To assess the prevalence of four key non-motor prodromal PD markers, and evaluate the sensitivity of case detection when non-motor screening tools for prodromal PD are implemented in an early clinical PD cohort. METHODS: Hyposmia (University of Pennsylvania smell identification test <=15th centile or Sniffin' Sticks at or <=10th centile corrected for age and sex), rapid eye movement sleep behaviour disorder (RBD questionnaire >4), constipation (<1 daily spontaneous bowel motion) and depression (Leeds >6) were recorded in recent onset PD cases, and proposed non-motor screening criteria applied. RESULTS: In 1,719 PD cases, mean age 68.6 years (SD 8.1), 65.5% male, mean disease duration 1.3 years (SD 0.9), 72.2% were hyposmic, 43.3% had RBD, 22.1% depression, and 21.5% constipation. 11.6% of cases had no key non-motor features, 38.8% one, 32.1% two, 15.5% three, and 2.0% all four. Increasing numbers of non-motor features were associated with younger age (p = 0.019), higher motor scores (p < 0.001), more postural instability gait difficulty (PIGD) (p < 0.001), greater cognitive impairment (p < 0.001) and higher total non-motor burden (p < 0.001). Cases with hyposmia alone were younger (p < 0.001), had less severe cognitive (p = 0.006) and other non-motor features (p < 0.001). All screening criteria selected younger patients (p = 0.001, p < 0.001), three of four greater overall non-motor burden (p = 0.005, p < 0.001), and inclusion of RBD more cognitive impairment (p = 0.003, p = 0.001) and PIGD (p = 0.004, p = 0.001). CONCLUSIONS: Varying sensitivity levels, and age and phenotype selectivity, are found when different non-motor screening methods to detect prodromal PD are applied to an early clinical PD cohort. PMID- 27003781 TI - Impact of Mood and Behavioral Disorders on Quality of Life in Parkinson's disease. AB - BACKGROUND: Mood symptoms negatively affect quality of life of Parkinson's disease (PD); however little is known about the impact of behavioral disorders such as impulse control disorders, and non-motor fluctuations on quality of life. OBJECTIVE: To assess the impact of mood and behavioral disorders on quality of life in PD. METHODS: 136 (84% male) PD were included (mean age: 61 +/- 8y; mean duration of disease: 8.8 +/- 5.4y). Mood symptoms, behavioral disorders and non motor fluctuations were detected and quantified using the recently validated "Ardouin Scale of Behavior in Parkinson's Disease". Motor symptoms were assessed using UPDRS and quality of life with the "39-item Parkinson's Disease Questionnaire". RESULTS: Both motor and non-motor factors significantly affected the quality of life of PD patients. Multivariate regression of the relationship between items of the quality of life questionnaire and the Ardouin Scale showed that alteration of patients' quality of life was strongly correlated with the presence of mood symptoms (such as depression, anxiety ...) and with non-motor fluctuations (especially in the OFF period). A significant correlation was also found between the number of symptoms and their severity, and the quality of life deterioration. Some behavioral disorders (compulsive buying / eating behavior) also negatively affected patient's quality of life to a lesser extent. Alternatively, excess in motivation and hobbyism behaviors had a positive impact on mobility and emotional well-being dimensions respectively of quality of life. CONCLUSIONS: This study shows the main impact of mood symptoms and non-motor fluctuations on worsening quality of life in PD. PMID- 27003782 TI - Roles of Cognitive Status and Intelligibility in Everyday Communication in People with Parkinson's Disease: A Systematic Review. AB - BACKGROUND: Communication is fundamental to human interaction and the development and maintenance of human relationships and is frequently affected in Parkinson's disease (PD). However, research and clinical practice have both tended to focus on impairment rather than participation aspects of communicative deficit in PD. In contrast, people with PD have reported that it is these participation aspects of communication that are of greatest concern to them rather than physical speech impairment. OBJECTIVE: To systematically review the existing body of evidence regarding the association between cognitive status and/or intelligibility and everyday communication in PD. METHODS: Five online databases were systematically searched in May 2015 (Medline Ovid, EMBASE, AMED, PsycINFO and CINAHL) and supplementary searches were also conducted. Two reviewers independently evaluated retrieved records for inclusion and then performed data extraction and quality assessment using standardised forms. Articles were eligible for inclusion if they were English-language original peer-reviewed research articles, book chapters or doctoral theses investigating the associations between at least one of cognitive status and level of intelligibility impairment and an everyday communication outcome in human participants with PD. RESULTS: 4816 unique records were identified through database searches with 16 additional records identified through supplementary searches. 41 articles were suitable for full-text screening and 15 articles (12 studies) met the eligibility criteria. 10 studies assessed the role of cognitive status and 9 found that participants with greater cognitive impairment had greater everyday communication difficulties. 4 studies assessed the role of intelligibility and all found that participants with greater intelligibility impairment had greater everyday communication difficulties, although effects were often weak and not consistent. CONCLUSIONS: Both cognitive status and intelligibility may be associated with everyday communicative outcomes in PD. The contribution of intelligibility to everyday communication appears to be of small magnitude, suggesting that other factors beyond predominantly motor driven impairment-level changes in intelligibility may play an important role in everyday communication difficulties in PD. PMID- 27003783 TI - Retrograde Axonal Degeneration in Parkinson Disease. AB - In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson's disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics. PMID- 27003785 TI - Are Stem Cell-Based Therapies for Parkinson's Disease Ready for the Clinic in 2016? AB - Recent news of an impending clinical cell transplantation trial in Parkinson's disease using parthenogenetic stem cells as a source of donor tissue have raised hopes in the patient community and sparked discussion in the research community. Based on discussions held by a global collaborative initiative on translation of stem cell therapy in Parkinson's disease, we have identified a set of key questions that we believe should be addressed ahead of every clinical stem cell based transplantation trial in this disorder. In this article, we first provide a short history of cell therapy in Parkinson's disease and briefly describe the current state-of-art regarding human stem cell-derived dopamine neurons for use in any patient trial. With this background information as a foundation, we then discuss each of the key questions in relation to the upcoming therapeutic trial and critically assess if the time is ripe for clinical translation of parthenogenetic stem cell technology in Parkinson's disease. PMID- 27003784 TI - Implication of Alpha-Synuclein Phosphorylation at S129 in Synucleinopathies: What Have We Learned in the Last Decade? AB - Abnormal accumulation of proteinaceous intraneuronal inclusions called Lewy bodies (LBs) is the neurpathological hallmark of Parkinson's disease (PD) and related synucleinopathies. These inclusions are mainly constituted of a presynaptic protein, alpha-synuclein (alpha-syn). Over the past decade, growing amounts of studies reported an aberrant accumulation of phosphorylated alpha-syn at the residue S129 (pS129) in the brain of patients suffering from PD, as well as in transgenic animal models of synucleinopathies. Whereas only a small fraction of alpha-syn (<4%) is phosphorylated in healthy brains, a dramatic accumulation of pS129 (>90%) has been observed within LBs, suggesting that this post-translational modification may play an important role in the regulation of alpha-syn aggregation, LBs formation and neuronal degeneration. However, whether phosphorylation at S129 suppresses or enhances alpha-syn aggregation and toxicity in vivo remains a subject of active debate. The answer to this question has important implications for understanding the role of phosphorylation in the pathogenesis of synucleinopathies and determining if targeting kinases or phosphatases could be a viable therapeutic strategy for the treatment of these devastating neurological disorders. In the present review, we explore recent findings from in vitro, cell-based assays and in vivo studies describing the potential implications of pS129 in the regulation of alpha-syn physiological functions, as well as its implication in synucleinopathies pathogenesis and diagnosis. PMID- 27003786 TI - "DBS means everything - for some time". Patients' Perspectives on Daily Life with Deep Brain Stimulation for Parkinson's Disease. PMID- 27003787 TI - Alterations in Activity-Dependent Neuroprotective Protein in Sporadic and Experimental Parkinson's Disease. AB - BACKGROUND: Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and neuronal survival. It is possible that intracellular alpha synuclein (alpha-syn) inclusions may be due to, or may cause, down-regulation of ADNP expression. OBJECTIVE: This study were to determine whether ADNP protein levels are altered in nigral dopaminergic neurons, establish whether ADNP alterations are associated with alpha-syn accumulation, and evaluate potential correlations between levels of ADNP expression and axonal transport motor proteins in sporadic and experimental Parkinson's disease (PD). METHODS: Twenty human brains from PD (n = 12) and age-matched controls (n = 8) and sixteen rat brains received alpha-synuclein gene (n = 8) or empty vector (n = 8) were analyzed using immunohistochemistry. The number of ADNP labeled nigral neurons were estimated with stereology and the levels of ADNP were determined using densitometry. RESULTS: Compared to age-matched controls, a marked reduction in ADNP protein levels was observed in neuromelanin-containing nigral neurons of PD. Reduced ADNP levels did no relate to the progression of PD symptoms, but instead occurred at early PD stages, before reductions in tyrosine hydroxylase could be detected. Reductions in ADNP were also positively correlated with alterations in axonal transport motor protein. Reductions in ADNP levels were recapitulated in a rat model of PD based on viral over-expression of human wild-type alpha synuclein, suggesting that ADNP reductions in PD are a direct result of alpha synuclein overexpression. CONCLUSION: These findings demonstrate that the down regulation of protein ADNP is an early pathological alteration and may contribute to dopaminergic neurodegeneration in PD. PMID- 27003788 TI - Transmission of Plasmodium falciparum by red blood cell transfusions in the management of sickle cell disease patients in Mali. PMID- 27003789 TI - Short-Term Retinal Sensitivity and Metamorphopsia Changes following Half-Fluence Photodynamic Therapy in Central Serous Chorioretinopathy. AB - PURPOSE: The aim of this study was to investigate the short-term retinal sensitivity and metamorphopsia changes after half-fluence photodynamic therapy (PDT) in patients with central serous chorioretinopathy (CSC). METHODS: Patients with acute CSC and evidence of angiographic leakage and subretinal fluid on optical coherence tomography (OCT) were enrolled. Before, and 1 week (W-1) and 2 months (M-2) after PDT, all patients underwent best-corrected visual acuity, enhanced depth imaging OCT, microperimetry (MP) and preferential hyperacuity perimetry (PHP). We considered 'affected' the Early Treatment of Diabetic Retinopathy Study (ETDRS) sectors showing a mean retinal thickness greater than 350 MUm on the baseline OCT thickness map. MP retinal sensitivity, PHP 'score' and retinal thickness were measured in each ETDRS 'affected sector'. Functional correlation between MP and PHP was also investigated. RESULTS: Twelve eyes of 12 patients were included. MP and PHP correlated with each other at baseline (p = 0.04) but not at W-1 (p = 0.12) and M-2 (p = 0.05). Mean MP retinal sensitivity slightly improved from 12.9 +/- 5.0 dB at baseline to 14.5 +/- 4.7 dB at M-2 (p = 0.2). The PHP score changed from 0.33 at baseline to 0.32 at M-2 (p = 0.3). In the ETDRS 'affected sectors', MP retinal sensitivity improved significantly from 12.9 +/- 5.0 dB at baseline to 14.5 +/- 4.7 dB at M-2 (p = 0.03), whereas the PHP score did not show significant changes over time. CONCLUSION: Half-fluence PDT achieved short-term improvement in the sensitivity of the retinal 'affected sectors' but did not influence metamorphopsia as measured on PHP in patients with acute CSC. PMID- 27003790 TI - Decoding and Reconstructing the Focus of Spatial Attention from the Topography of Alpha-band Oscillations. AB - Many aspects of perception and cognition are supported by activity in neural populations that are tuned to different stimulus features (e.g., orientation, spatial location, color). Goal-directed behavior, such as sustained attention, requires a mechanism for the selective prioritization of contextually appropriate representations. A candidate mechanism of sustained spatial attention is neural activity in the alpha band (8-13 Hz), whose power in the human EEG covaries with the focus of covert attention. Here, we applied an inverted encoding model to assess whether spatially selective neural responses could be recovered from the topography of alpha-band oscillations during spatial attention. Participants were cued to covertly attend to one of six spatial locations arranged concentrically around fixation while EEG was recorded. A linear classifier applied to EEG data during sustained attention demonstrated successful classification of the attended location from the topography of alpha power, although not from other frequency bands. We next sought to reconstruct the focus of spatial attention over time by applying inverted encoding models to the topography of alpha power and phase. Alpha power, but not phase, allowed for robust reconstructions of the specific attended location beginning around 450 msec postcue, an onset earlier than previous reports. These results demonstrate that posterior alpha-band oscillations can be used to track activity in feature-selective neural populations with high temporal precision during the deployment of covert spatial attention. PMID- 27003791 TI - Time-dependent combinatory effects of active mechanical loading and passive topographical cues on cell orientation. AB - Mechanical stretching and topographical cues are both effective mechanical stimulations for regulating cell morphology, orientation, and behaviors. The competition of these two mechanical stimulations remains largely underexplored. Previous studies have suggested that a small cyclic mechanical strain is not able to reorient cells that have been pre-aligned by relatively large linear microstructures, but can reorient those pre-aligned by small linear micro/nanostructures if the characteristic dimension of these structures is below a certain threshold. Likewise, for micro/nanostructures with a given characteristic dimension, the strain must exceed a certain magnitude to overrule the topographic cues. There are however no in-depth investigations of such "thresholds" due to the lack of close examination of dynamic cell orientation during and shortly after the mechanical loading. In this study, the time dependent combinatory effects of active and passive mechanical stimulations on cell orientation are investigated by developing a micromechanical stimulator. The results show that the cells pre-aligned by linear micro/nanostructures can be altered by cyclic in-plane strain, regardless of the structure size. During the loading, the micro/nanostructures can resist the reorientation effects by cyclic in-plane strain while the resistive capability (measured by the mean orientation angle change and the reorientation speed) increases with the increasing characteristic dimension. The micro/nanostructures also can recover the cell orientation after the cessation of cyclic in-plane strain, while the recovering capability increases with the characteristic dimension. The previously observed thresholds are largely dependent on the observation time points. In order to accurately evaluate the combinatory effects of the two mechanical stimulations, observations during the active loading with a short time interval or endpoint observations shortly after the loading are preferred. This study provides a microengineering solution to investigate the time-dependent combinatory effects of the active and passive mechanical stimulations and is expected to enhance our understanding of cell responses to complex mechanical environments. Biotechnol. Bioeng. 2016;113: 2191-2201. (c) 2016 Wiley Periodicals, Inc. PMID- 27003792 TI - The impact of compaction and leachate recirculation on waste degradation in simulated landfills. AB - This study investigated the impact of compaction and leachate recirculation on anaerobic degradation of municipal solid waste (MSW) at different methane formation phases. Two stainless steel lysimeters, C1 and C2, were constructed by equipping a hydraulic cylinder to apply pressure load (42kPs) on the MSW. When MSW started to produce methane, C1 was compacted, but C2 was compacted when the methane production rate declined from the peak generation rate. Methane production of C1was inhibited by the compaction and resulted in producing a total of 106L methane (44L/kgVS). However, the compaction in C2 promoted MSW degradation resulting in producing a total of 298L methane (125L/kgVS). The concentrations of volatile fatty acids and chemical oxygen demand showed temporary increases, when pressure load was applied. It was considered that the increased substrate accessibility within MSW by compaction could cause either the inhibition or the enhancement of methane production, depending the tolerability of methanogens on the acidic inhibition. Leachate recirculation also gave positive effects on methane generation from wet waste in the decelerated methanogenic phase by increasing mass transfer and the concentrations of volatile fatty acids. PMID- 27003793 TI - Volatile fatty acids produced by co-fermentation of waste activated sludge and henna plant biomass. AB - Anaerobic co-fermentation of waste activated sludge (WAS) and henna plant biomass (HPB) for the enhanced production of volatile fatty acids (VFAs) was investigated. The results indicated that VFAs was the main constituents of the released organics; the accumulation of VFAs was much higher than that of soluble carbohydrates and proteins. HPB was an advantageous substrate compared to WAS for VFAs production; and the maximum VFAs concentration in an HPB mono-fermentation system was about 2.6-fold that in a WAS mono-fermentation system. In co fermentation systems, VFAs accumulation was positively related to the proportion of HPB in the mixed substrate, and the accumulated VFAs concentrations doubled when HPB was increased from 25% to 75%. HPB not only adjust the C/N ratio; the associated and/or released lawsone might also have a positive electron-shuttling effect on VFAs production. PMID- 27003794 TI - Phosphorus removal and recovery from domestic wastewater in a novel process of enhanced biological phosphorus removal coupled with crystallization. AB - A new process of enhanced biological phosphorus removal coupled with crystallization recovery of phosphorus was developed here, where the feasibility of nutrients removal and potential for phosphorus recovery from domestic wastewater was further assessed. Results showed that an excellent nutrients removal and phosphorus recovery performance was achieved, in which the averaged COD, PO4(3-)-P and NO3(-)-N removal efficiencies were 82.6%, 87.5% and 91.6%, respectively and a total of 59.3% of phosphorus was recovered as hydroxyapatite. What's more, crystallization recovery of phosphorus greatly enhanced the biological phosphorus removal efficiency. After the incorporation of the phosphorus recovery column via side-stream, the phosphorus concentration of effluent was significantly decreased ranging from 1.24mg/L to 0.85mg/L, 0.52mg/L and 0.41mg/L at the lateral flow ratios of 0, 0.1, 0.2 and 0.3, respectively. The results obtained here would be beneficial to provide a prospective alternative for phosphorus removal and recovery from wastewater. PMID- 27003795 TI - Cerebellar transcranial direct current stimulation in children with ataxic cerebral palsy: A sham-controlled, crossover, pilot study. AB - OBJECTIVE: The aim of the present study was to analyze the use of anodal tDCS of the cerebellar region combined with treadmill training to improve balance and functional performance in children with ataxic cerebral palsy. DESIGN: Single blind, sham-controlled, crossover, pilot study. SETTING: Rehabilitation center and research motion analysis laboratory. PARTICIPANTS: Children (N = 6) with ataxic cerebral palsy and balance deficit. MAIN OUTCOME MEASURES: Static balance (oscillations of the center of pressure), functional balance (Pediatric Balance Scale) and functional performance (Pediatric Evaluation of Disability Inventory) were evaluated. RESULTS: Significant reductions occurred in oscillations of the center of pressure with eyes closed after active anodal tDCS only. The effects of treadmill training on functional balance and functional performance in mobility were maintained in the active tDCS group only. CONCLUSION: These preliminary data support the notion that anodal tDCS of the cerebellar region combined with treadmill training improves balance in children with ataxic cerebral palsy. PMID- 27003796 TI - Comparing Raman and fluorescence lifetime spectroscopy from human atherosclerotic lesions using a bimodal probe. AB - Fluorescence lifetime imaging (FLIm) and Raman spectroscopy are two promising methods to support morphological intravascular imaging techniques with chemical contrast. Both approaches are complementary and may also be used in combination with OCT/IVUS to add chemical specificity to these morphologic intravascular imaging modalities. In this contribution, both modalities were simultaneously acquired from two human coronary specimens using a bimodal probe. A previously trained SVM model was used to interpret the fluorescence lifetime data; integrated band intensities displayed in RGB false color images were used to interpret the Raman data. Both modalities demonstrate unique strengths and weaknesses and these will be discussed in comparison to histologic analyses from the two coronary arteries imaged. PMID- 27003798 TI - Novel Signal-Amplified Fenitrothion Electrochemical Assay, Based on Glassy Carbon Electrode Modified with Dispersed Graphene Oxide. AB - A novel signal-amplified electrochemical assay for the determination of fenitrothion was developed, based on the redox behaviour of organophosphorus pesticides on a glassy carbon working electrode. The electrode was modified using graphene oxide dispersion. The electrochemical response of fenitrothion at the modified electrode was investigated using cyclic voltammetry, current-time curves, and square-wave voltammetry. Experimental parameters, namely the accumulation conditions, pH value, and volume of dispersed material, were optimised. Under the optimum conditions, a good linear relationship was obtained between the oxidation peak current and the fenitrothion concentration. The linear range was 1-400 ng.mL(-1), with a detection limit of 0.1 ng.mL(-1) (signal-to nose ratio = 3). The high sensitivity of the sensor was demonstrated by determining fenitrothion in pakchoi samples. PMID- 27003797 TI - Epidemiology of rotavirus A diarrhea in Chokwe, Southern Mozambique, from February to September, 2011. AB - Acute diarrhea disease caused by Rotaviruses A (RVA) is still the leading cause of morbidity and mortality in children <=5 years old in developing countries. An exploratory cross-sectional study was conducted between February and September, 2011 to determine the proportion of acute diarrhea caused by RVA. A total of 254 stool specimens were collected from children <=5 years old with acute diarrhea, including outpatients (222 children) and inpatients (32 children), in three local health centers in Chokwe District, Gaza Province, South of Mozambique. RVA antigens were detected using enzyme immunoassay (EIA); the RVA G (VP7) and P (VP4) genotypes were determined by RT-PCR or analysis sequencing. Sixty (24%) out of 254 fecal specimens were positive for RVA by EIA; being 58 (97%) from children <=2 years of age. RVA prevalence peaks in June and July (coldest and drier months) and the G[P] binary combination observed were G12P[8] (57%); G1P[8] (9%); G12P[6] (6%); and 2% for each of the following genotypes: G1P[6], G2P[6] G4P[6], and G9P[8]. Non-Typeable (NT) G and/or P genotypes were observed as follows: G12P [NT] (6%); G1P [NT], G3P[NT] and GNTP[NT] (4%). Considering the different GP combinations, G12 represented 67% of the genotypes. This is the first data showing the diversity of RVA genotypes in Mozambique highlighting the epidemiological importance of these viruses in acute diarrhea cases in children <=2 years old. In addition, these findings will provide a baseline data before the introduction of the RVA monovalent (Rotarix((r)) ) vaccine in the National Immunization Program in September 2015. J. Med. Virol. 88:1751-1758, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27003799 TI - Overproduction of Indole-3-Acetic Acid in Free-Living Rhizobia Induces Transcriptional Changes Resembling Those Occurring in Nodule Bacteroids. AB - Free-living bacteria grown under aerobic conditions were used to investigate, by next-generation RNA sequencing analysis, the transcriptional profiles of Sinorhizobium meliloti wild-type 1021 and its derivative, RD64, overproducing the main auxin indole-3-acetic acid (IAA). Among the upregulated genes in RD64 cells, we detected the main nitrogen-fixation regulator fixJ, the two intermediate regulators fixK and nifA, and several other genes known to be FixJ targets. The gene coding for the sigma factor RpoH1 and other genes involved in stress response, regulated in a RpoH1-dependent manner in S. meliloti, were also induced in RD64 cells. Under microaerobic condition, quantitative real-time polymerase chain reaction analysis revealed that the genes fixJL and nifA were up-regulated in RD64 cells as compared with 1021 cells. This work provided evidence that the overexpression of IAA in S. meliloti free-living cells induced many of the transcriptional changes that normally occur in nitrogen-fixing root nodule. PMID- 27003800 TI - Global Pattern of Gene Expression of Xanthomonas axonopodis pv. glycines Within Soybean Leaves. AB - To better understand the behavior of Xanthomonas axonopodis pv. glycines, the causal agent of bacterial pustule of soybean within its host, its global transcriptome within soybean leaves was compared with that in a minimal medium in vitro, using deep sequencing of mRNA. Of 5,062 genes predicted from a draft genome of X. axonopodis pv. glycines, 534 were up-regulated in the plant, while 289 were down-regulated. Genes encoding YapH, a cell-surface adhesin, as well as several others encoding cell-surface proteins, were down-regulated in soybean. Many genes encoding the type III secretion system and effector proteins, cell wall-degrading enzymes and phosphate transporter proteins were strongly expressed at early stages of infection. Several genes encoding RND multidrug efflux pumps were induced in planta and by isoflavonoids in vitro and were required for full virulence of X. axonopodis pv. glycines, as well as resistance to soybean phytoalexins. Genes encoding consumption of malonate, a compound abundant in soybean, were induced in planta and by malonate in vitro. Disruption of the malonate decarboxylase operon blocked growth in minimal media with malonate as the sole carbon source but did not significantly alter growth in soybean, apparently because genes for sucrose and fructose uptake were also induced in planta. Many genes involved in phosphate metabolism and uptake were induced in planta. While disruption of genes encoding high-affinity phosphate transport did not alter growth in media varying in phosphate concentration, the mutants were severely attenuated for growth in soybean. This global transcriptional profiling has provided insight into both the intercellular environment of this soybean pathogen and traits used by X. axonopodis pv. glycines to promote disease. PMID- 27003801 TI - Endoscopic antralplasty for severe gastric stasis after wide endoscopic submucosal dissection in the antrum. AB - A 75-year-old female underwent esophagogastroduodenoscopy, revealing a widely spreading tumor occupying the anterior wall, lesser curvature, and posterior wall of the antrum and lower body. Endoscopic submucosal dissection was performed and resulted in more than five-sixths circumferential antral mucosal resection. One month later, she complained of nausea, vomiting, and abdominal distention. Endoscopy showed residual food in the stomach and deformation of the antrum with traction toward the contracted scar in the lesser curvature. The pyloric ring could not be seen from the antrum although the endoscope was able to pass easily beyond the area of deformation and the pyloric ring was intact. Despite repeated endoscopic balloon dilations, the patient's symptoms remained refractory. The problem was speculated to be not due to any potential stricture but to antrum deformation resulting from the traction force toward the healing ulcer. We hypothesized that an additional countertraction force opposite the previous ESD site might resolve the problem, and ESD of approximately 2.5 cm size was performed in the greater curvature of the antrum. Along with development of a scar, traction toward the greater curvature was added, and the pyloric ring could be observed on repeat esophagogastroduodenoscopy. The symptoms were also gradually ameliorated. Afterwards, the endoscopic findings have now been unchanged during 7 years of follow-up. PMID- 27003802 TI - Gonadal Imaging in Endocrine Disorders. AB - Ultrasound (US) is the most widely available method of diagnostic imaging for the evaluation and characterization of gonadal lesions and is usually the method of choice because of its high accuracy, low cost and wide availability. Today's high resolution images allow for a confident diagnosis of many scrotal and adnexal lesions, with high sensitivity and specificity. Magnetic resonance imaging (MRI) is reliable in the detection of gonadal lesions in males, allowing the differentiation into testicular or nontesticular lesions, and their characterization. It is also an accurate and cost-effective diagnostic adjunct in those patients with solid scrotal lesions for whom the findings of clinical and US evaluations are inconclusive. In females, MRI is recommended as a second-line investigation for the characterization of complex adnexal masses that are indeterminate on US. In this review, gonadal pathologies related with the steroidogenic and gametogenic function of the testes and ovaries will be discussed. The main imaging features of benign and malignant lesions will also be presented. PMID- 27003803 TI - Correction: A Voltage-Based STDP Rule Combined with Fast BCM-Like Metaplasticity Accounts for LTP and Concurrent "Heterosynaptic" LTD in the Dentate Gyrus In Vivo. PMID- 27003804 TI - Genotoxic Effects Induced by Cd(+2), Cr(+6), Cu(+2) in the Gill and Liver of Odontesthes bonariensis (Piscies, Atherinopsidae). AB - Genotoxic effects of Cd(+2), Cr(+6), and Cu(+2) on the gill and liver of the Argentinean Silverside (Odontesthes bonariensis) were studied using the comet assay and in relation with the metal tissue accumulation. Fish were exposed to three waterborne concentrations of each metal for 2 and 16 days. Genotoxicity was assessed by the single cell gel electrophoresis (comet assay). After 2 days, significant increase of the genetic damage index (GDI) was only observed in the gill of fish exposed to Cr(+6) and Cu(+2), and the LOECs were 2160 nM and 921.1 nM, respectively. The gill LOEC for Cd(+2) by 16 days was 9.4 nM. In the liver, LOECs were obtained only for Cd(+2) and Cr(+6) and were 9.4 and 2160 nM, respectively. The three metals were able to induce genotoxic effects at environmentally relevant concentrations and the gill was the most sensitive organ. PMID- 27003805 TI - Active Sphagnum girgensohnii Russow Moss Biomonitoring of an Industrial Site in Romania: Temporal Variation in the Elemental Content. AB - The moss-bag transplant technique was used to investigate the kinetics of the accumulation of 38 elements in Sphagnum girgensohni moss samples in the highly polluted municipality of Baia Mare, Romania. The moss samples collected from the unpolluted Vitosha Mountain Natural Reserve, Bulgaria, were analyzed after 1, 2, 3, and 4 months of exposure, respectively. The ANOVA method was used to assay the statistical significance of the observed changes in elemental content, as determined by neutron activation analysis. The content of Zn, Se, As, Ag, Cd, and Sb increased steadily, while that of physiologically active K and Cl, as well as Rb and Cs, decreased exponentially. The study showed that an adequate application of the moss transplant technique in an urban environment should consider the exposure time as a critical parameter, since particular elements are depleted in the moss at sites with high atmospheric loading of metals. PMID- 27003806 TI - Comparison of Measured and Predicted Bioconcentration Estimates of Pharmaceuticals in Fish Plasma and Prediction of Chronic Risk. AB - Evaluation of the environmental risk of human pharmaceuticals is now a mandatory component in all new drug applications submitted for approval in EU. With >3000 drugs currently in use, it is not feasible to test each active ingredient, so prioritization is key. A recent review has listed nine prioritization approaches including the fish plasma model (FPM). The present paper focuses on comparison of measured and predicted fish plasma bioconcentration factors (BCFs) of four common over-the-counter/prescribed pharmaceuticals: norethindrone (NET), ibuprofen (IBU), verapamil (VER) and clozapine (CLZ). The measured data were obtained from the earlier published fish BCF studies. The measured BCF estimates of NET, IBU, VER and CLZ were 13.4, 1.4, 0.7 and 31.2, while the corresponding predicted BCFs (based log Kow at pH 7) were 19, 1.0, 7.6 and 30, respectively. These results indicate that the predicted BCFs matched well the measured values. The BCF estimates were used to calculate the human: fish plasma concentration ratios of each drug to predict potential risk to fish. The plasma ratio results show the following order of risk potential for fish: NET > CLZ > VER > IBU. The FPM has value in prioritizing pharmaceutical products for ecotoxicological assessments. PMID- 27003807 TI - Computational-Model-Based Analysis of Context Effects on Harmonic Expectancy. AB - Expectancy for an upcoming musical chord, harmonic expectancy, is supposedly based on automatic activation of tonal knowledge. Since previous studies implicitly relied on interpretations based on Western music theory, the underlying computational processes involved in harmonic expectancy and how it relates to tonality need further clarification. In particular, short chord sequences which cannot lead to unique keys are difficult to interpret in music theory. In this study, we examined effects of preceding chords on harmonic expectancy from a computational perspective, using stochastic modeling. We conducted a behavioral experiment, in which participants listened to short chord sequences and evaluated the subjective relatedness of the last chord to the preceding ones. Based on these judgments, we built stochastic models of the computational process underlying harmonic expectancy. Following this, we compared the explanatory power of the models. Our results imply that, even when listening to short chord sequences, internally constructed and updated tonal assumptions determine the expectancy of the upcoming chord. PMID- 27003811 TI - Usefulness of the radiological planning for hearing preservation surgery in vestibular schwannoma. AB - PURPOSE: During vestibular schwannoma surgery there is a risk of endolymphatic duct and sac injury, which may cause a loss or a deterioration of hearing. The goal of the study was to evaluate the empirical utility of presurgical planning using CT with the bone window for the hearing preservation surgery. METHODS: The study was performed on 14 human temporal bones. CT scans with the bone window were obtained in the standard position. Safe drilling line was evaluated and after that drilling distances were analysed: the lateral drilling distance, total length of internal acoustic meatus, drilled length of internal acoustic meatus. After this, a surgical exposure was performed, using size of a drill tip as measuring scale. The dura was excised and endolymphatic duct was injected with a latex. Revision of the internal acoustic meatus was performed with the use of a microscope. RESULTS: Mean results of safe drilling coefficients were: lateral drilling distance: 10 +/- 2 mm, total length of internal acoustic meatus: 9 +/- 2 mm, drilled length of internal acoustic meatus: 7 +/- 2 mm. In all cases, no endolymphatic duct injury was observed. CONCLUSIONS: Preoperative radiological planning using the safe drilling coefficients is of value for the hearing preservation surgery in vestibular schwannoma. The size of the drilling tip may be used as an intraoperative measuring scale during this procedure. However, CT with a bone window is a necessary tool for the purposes of this procedure. PMID- 27003812 TI - Transient Ocular Wavefront Data in Type 1 Diabetes Mellitus. AB - PURPOSE: We report transient ocular wavefront and blood glucose data for one patient with acute type 1 diabetes mellitus after the treatment with insulin has been initiated. CASE REPORT: The wavefront data for both eyes of a 34-year-old male patient were examined by a Hartmann-Shack wavefront sensor. Refraction data and higher-order aberrations were recorded during 130 days for eyes in natural conditions, without cycloplegia. At the beginning, we sampled data every 3 to 4 days and enlarged the intervals, when values settled. In total, we report 20 measurements and 1 baseline entry. Blood glucose levels were recorded at least six times a day during the complete period. For the equivalent sphere, we recorded a bilateral hyperopic shift of 5 D from -2.75 DS to +2.25 DS, followed by a reverse myopic shift of the same amount. The equivalent sphere peaked about 15 to 18 days after the treatment with insulin had begun. Cylinder values kept remarkably stable. Higher-order aberrations are dominated by the spherical aberration. The Zernike coefficient c12 for both eyes changed substantially from OD 0.036 MUm and OS 0.062 MUm to OD 0.24 MUm and OS 0.22 MUm (5 mm pupil diameter) following the time pattern of the equivalent sphere. About 60 days after they had reached their peak, all refraction values and higher-order aberrations stabilized at their baseline levels. The baseline was defined by records taken 4 years before the treatment with insulin was commenced. CONCLUSIONS: Wavefront aberrometry gives quantitative insights in the transient alteration and recovering of the eye's optics whilst the therapy of acute type 1 diabetes mellitus is being initiated. The data of this case support the assumption that variations in the crystalline lens, most probably the modification of its refractive gradient index, as a cause for the transient behavior. An explanation is still missing. PMID- 27003810 TI - Pancreaticobiliary maljunction and choledochal cysts: from embryogenesis to therapeutics aspects. AB - Pancreaticobiliary maljunction (PBM) and choledochal cysts (CC) are rare and little-known diseases. Several definitions have been proposed for the PBM, but the most widely accepted is an excessive length of the common pancreaticobiliary duct due to the abnormal convergence of the pancreatic and biliary ducts out of the duodenal wall. This anomaly, thought to develop during embryogenesis, is associated with a loss of regulation of the Oddi's sphincter leading to a pancreaticobiliary or biliopancreatic backflow. This reflux could be responsible, or associated with cystic dilatation of the bile ducts and biliary tract cancers, to various biliary or pancreatic events such as cholangitis or pancreatitis. For the diagnosis of PBM, magnetic resonance cholangiopancreatography has now become the gold standard as a noninvasive imaging tool. However, the main risk of PBM is the development of bile duct cancer, most often on a distended area. PBM without CC increase the occurrence of gallbladder cancer and require a preventive cholecystectomy. Surgical treatment of PBM with concomitant CC is more complex and depends on localization of the dilatation(s) as reported in the Todani's classification. This review describes the pathogenesis, embryogenesis, clinical features, investigation and management of PBM and CC. PMID- 27003813 TI - Effect of Direct Glare on Orbicularis Oculi and Trapezius During Computer Reading. AB - PURPOSE: Unfavorable visual conditions during computer work may affect development of both eyestrain and musculoskeletal pain in the neck and shoulder area. The aim of the study was to investigate how direct glare affects symptom development, muscle activity, and muscle blood flow in m. orbicularis oculi and m. trapezius during reading on a computer screen. METHODS: Fifteen healthy young adults with normal binocular vision read text on a computer screen at an optimized computer workplace, 30 minutes with glare exposure and 30 minutes with appropriate lighting. Postural angles were continuously registered. Development of eye symptoms and musculoskeletal pain in the neck and shoulder area were recorded using VAS scales. Muscle activity and muscle blood flow were measured continuously using electromyography and photoplethysmography, respectively. RESULTS: Glare exposure resulted in significantly more pronounced eye pain, increased orbicularis muscle activity, and increased trapezius blood flow compared to reading with appropriate lighting. There were no significant differences in posture between the two light conditions. There were also significant associations between orbicularis oculi activity and both trapezius blood flow and neck pain during both conditions. CONCLUSIONS: Results from the current study show that direct glare conditions cause increased eyestrain and orbicularis oculi contraction during reading on a computer screen. This study also indicates that exposure to direct glare affects the trapezius muscle, possibly by an interaction between the visual system, sympathetic nervous system, and head-stabilizing muscles. In addition, there were associations between the use of orbicularis oculi, trapezius blood flow, and development of neck pain independent of the lighting. PMID- 27003814 TI - Pharmacologic Management of Pressure-Induced Stromal Keratopathy after LASIK. AB - PURPOSE: To emphasize the importance of anticipation of pressure-induced stromal keratopathy (PISK) in eyes with a previous history of LASIK. CASE REPORT: A 40 year-old man developed LASIK-related pressure-induced stromal keratopathy after uneventful phacoemulsification (Phaco) and intraocular lens (IOL) implantation in his left eye. With immediate discontinuation of the steroid drops and initiation of antiglaucoma medication, his visual acuity, interface edema, and haze improved rapidly. One year later, during Phaco with IOL implantation in his other eye, with anticipation of a similar LASIK-related pressure-induced stromal keratopathy, a very brief course of soft steroid therapy was given together with antiglaucoma medication. Intraocular pressure elevation was avoided, and no interface edema or haze was observed. CONCLUSIONS: This case illustrates that the risk for LASIK-related pressure-induced stromal keratopathy may be reduced with appropriate precautions. PMID- 27003815 TI - Communication Predicts Medication Self-Efficacy in Glaucoma Patients. AB - PURPOSE: Medication self-efficacy, or patients' confidence that they can perform medication-related behaviors, is associated with better glaucoma medication adherence. Little is known about how to enhance glaucoma patients' medication self-efficacy. Our purpose is to examine whether patient-provider communication increases glaucoma patients' medication self-efficacy. METHODS: During an 8-month cohort study of 279 glaucoma patients and 15 providers, two office visits were videotape-recorded, transcribed, and coded for six patient-provider communication behaviors. A validated scale was used at baseline and 8-month follow-up to assess patients' confidence in overcoming adherence barriers (adherence barriers self efficacy) and carrying out tasks to use eye drops correctly (eye drop task self efficacy). We ran two generalized estimating equations to examine whether more frequent patient-provider communication during office visits predicted increased patient adherence barriers self-efficacy and eye drop task self-efficacy at 8 month follow-up. RESULTS: For each additional topic providers educated about, patients reported an average increase of 0.35 in self-efficacy in overcoming adherence barriers (p < 0.001). Patients also reported an average increase of 1.01 points in eye drop task self-efficacy when providers asked about patients' views of glaucoma and its treatment versus not (p < 0.001). Patients who asked more medication questions (p < 0.001) and African-American patients (p < 0.05) reported lower adherence barriers self-efficacy by 0.30 and 2.15 points, respectively. Women had a 0.63 lower eye drop task self-efficacy than men (p < 0.05). CONCLUSIONS: When providers educate glaucoma patients and assess patient views about glaucoma and its treatment, patients report higher medication self efficacy. Providers should be aware that patients who ask more medication questions may have less confidence in their ability to overcome barriers to adherence. PMID- 27003816 TI - The Safety of Metoclopramide in Children: A Systematic Review and Meta-Analysis. AB - INTRODUCTION: Metoclopramide is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV) and for CINV prophylaxis in children. The drug regulatory agencies of Canada and the EU have revised the labelling of metoclopramide to contraindicate its use in children aged <1 year and to caution against its use in children aged <5 years and its duration of use beyond 5 days. OBJECTIVE: This review describes the safety of metoclopramide in children when given for any indication. METHODS: We conducted electronic searches in MEDLINE and Embase as of 9 March 2015. All studies in English reporting adverse effects associated with the use of metoclopramide in children (aged <=18 years) were included. Adverse effects that had a cumulative incidence of at least 1 % and were reported in prospective studies were synthesized. RESULTS: A total of 108 (57 prospective) studies involving 2699 patients (2745 metoclopramide courses) were included. The most common adverse effects reported in prospective studies of metoclopramide in children were extrapyramidal symptoms (EPS; 9 %, 95 % confidence interval [CI] 5-17), diarrhea (6 %, 95 % CI 4-9), and sedation (multiple-dose studies: 6 %, 95 % CI 3-12). Dysrhythmia, respiratory distress/arrest, neuroleptic malignant syndrome, and tardive dyskinesia were rarely associated with metoclopramide use. LIMITATIONS: The definitions of adverse effects reported in the included studies were heterogeneous, and the risk of bias in most studies was moderate. CONCLUSIONS: The most commonly reported adverse effects associated with the use of metoclopramide in children-EPS, diarrhea, and sedation-were reversible and of no long-term significance. Adverse effects that were life threatening or slow to resolve were rarely associated with its use in children. PMID- 27003817 TI - Linking MedDRA((r))-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors. AB - INTRODUCTION: A translational bioinformatics challenge exists in connecting population and individual clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA((r))) is the default dictionary for adverse event (AE) reporting in the US Food and Drug Administration Adverse Event Reporting System (FAERS). The ontology of adverse events (OAE) represents AEs as pathological processes occurring after drug exposures. OBJECTIVES: The aim of this work was to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA((r)) in FAERS data analysis. We investigated the AEs associated with tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The five selected TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. RESULTS: Statistical analysis of FAERS data identified 1053 distinct MedDRA((r)) terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA((r)). The data integration to provide insights into molecular mechanisms of drug-associated AEs was performed by including linkages in OAE for all related AE terms to MedDRA((r)) and the existing ontologies, including the human phenotype ontology (HP), Uber anatomy ontology (UBERON), and gene ontology (GO). Sixteen AEs were shared by all five TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed "cardiac failure" using the relations established in OAE with other ontologies and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. CONCLUSION: By expanding the existing OAE ontological design, our TKI use case demonstrated that the combination of OAE and MedDRA((r)) provides a semantic framework to link clinical phenotypes of adverse drug events to biological mechanisms. PMID- 27003818 TI - Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling. AB - Polo-like kinase 1 (PLK1) is a key cell cycle regulator implicated in the development of various cancers, including prostate cancer. However, the functions of PLK1 beyond cell cycle regulation remain poorly characterized. Here, we report that PLK1 overexpression in prostate epithelial cells triggers oncogenic transformation. It also results in dramatic transcriptional reprogramming of the cells, leading to epithelial-to-mesenchymal transition (EMT) and stimulation of cell migration and invasion. Consistently, PLK1 downregulation in metastatic prostate cancer cells enhances epithelial characteristics and inhibits cell motility. The signaling mechanisms underlying the observed cellular effects of PLK1 involve direct PLK1-dependent phosphorylation of CRAF with subsequent stimulation of the MEK1/2-ERK1/2-Fra1-ZEB1/2 signaling pathway. Our findings highlight novel non-canonical functions of PLK1 as a key regulator of EMT and cell motility in normal prostate epithelium and prostate cancer. This study also uncovers a previously unanticipated role of PLK1 as a potent activator of MAPK signaling. PMID- 27003819 TI - The aspiration saga during primary PCI for STEMI: yes or no or sometimes? AB - The primary objective of therapeutic interventions in patients with acute ST elevation myocardial infarction (STEMI) is to rapidly normalize tissue-level perfusion in order to prevent myocardial cell death. The preferred method for achieving this goal is by performing primary percutaneous coronary intervention (PCI). A major hurdle is the frequent dislodgement of particulate matter from the culprit lesion, which may embolize downstream and occlude the distal microvessels. Microvascular obstruction prevents myocardial reperfusion despite achievement of epicardial coronary artery patency and is associated with adverse clinical outcomes. A potential method for decreasing distal coronary embolization and microvascular obstruction is by aspiration thrombectomy, a technique designed to remove the particulate matter from the lesion prior to stent implantation. Initial studies of thrombectomy reported favorable outcomes in STEMI patients undergoing primary PCI, however subsequent large multicenter randomized trials failed to support these findings. This manuscript reviews the current data regarding aspiration thrombectomy in STEMI coronary interventions and discusses the role of this strategy in current practice. PMID- 27003820 TI - Impact of comorbidity on outcome in kidney transplant recipients: a retrospective study in Italy. AB - The aim of this study was to relate in-hospital mortality (IHM), cardiovascular events (CVEs) and non-immunologic comorbidity evaluated on the basis of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codification, in Italian kidney transplant recipients (KTRs). We evaluated IHM and admissions due to CVEs between 2000 and 2013 recorded in the database of the region Emilia Romagna. The Elixhauser score was calculated for evaluation of non-immunologic comorbidity. Three main outcomes (i.e. IHM, admission due to major CVEs and combined outcome) were the dependent variables of the multivariate models, while age, gender and Elixhauser score were the independent ones. During the examined period, a total of 9063 admissions in 3648 KTRs were recorded; 1945 patients were males (53.3 %) and 1703 females (46.7 %) and the mean age was 52.9 +/- 13.1 years. The non-immunological impaired status of the KTRs, examined by the Elixhauser score, was 3.88 +/- 4.29. During the 14 year follow-up period, IHM for any cause was 3.2 % (n = 117), and admissions due to CVEs were 527 (5.8 %). Age and comorbidity were independently associated with CVEs, IHM and the combined outcome. Male gender was independently associated with IHM and combined outcome, but not with CVEs. Evaluation of non-immunological comorbidity is important in KTRs and identification of high-risk patients for major clinical events could improve outcome. Moreover, comorbidity could be even more important in chronic kidney disease patients who are waiting for a kidney transplant. PMID- 27003821 TI - The Role of Dynamic Contrast-Enhanced MR in Evaluating Level III Collateral Circulation in a Rat Model of Acute Ischemic Stroke. AB - The study aimed to investigate the correlations between parameters of permeability magnetic resonance (MR) and the intensity of vasculature in the focal ischemic cortex of a rat model of middle cerebral artery occlusion. In the present study, sham operation or ischemic-reperfusion with tissue plasminogen activator (tPA) thrombolysis were performed in rats. Cranial MR scans and brain tissue samples were obtained from all animals. Brain slices were stained for immunohistological analyses with confocal fluorescence microscopy, and the intensities of microvessels and capillaries were calculated. Consistency between collateral circulation imaging classification and pathological vascular density was analyzed. We found that the K trans value and capillary intensity have the similar trends of declining and increasing, according to different time points, if compared with the sham operation group (P < 0.05). Permeability parameters have better correlations with capillary intensity, and K trans value had the best correlation at 4.5 h (kappa = 0.764, P < 0.001), while injection area under curve (IAUC) at 7 days (kappa = 0.725, P < 0.001). Susceptibility-weighted imaging (SWI) exhibited better correlation with microvessel intensity at both 3 days (kappa = 0.715, P < 0.001) and 7 days (kappa = 0.719, P < 0.001). In conclusion, the permeability parameters, such as IAUC and K trans map, can quantitatively assess capillary intensity, which may indicate angiogenesis categorized as level III collateral circulation after ischemic stroke. PMID- 27003822 TI - NCAM-140 Translocation into Lipid Rafts Mediates the Neuroprotective Effects of GDNF. AB - Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for substantia nigra dopaminergic (DA) neuronal cells. Recent studies have demonstrated that neural cell adhesion molecule functions as a signal transduction receptor for GDNF. The purpose of this study is to reveal whether neural cell adhesion molecule (NCAM) mediates the protective effects of GDNF on DA neuronal cells and further explore the mechanisms involved. We utilized SH SY5Y cell line to establish a model of 6-hydroxydopamine (6-OHDA)-injured DA neuronal cells. Lentiviral vectors were constructed to knockdown or overexpress NCAM-140, and a density gradient centrifugation method was employed to separate membrane lipid rafts. 3-(4,5-Dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis, and western blotting were used to evaluate the protective effects of GDNF. The results showed that GDNF could protect 6-OHDA-injured SH-SY5Y cells via improving cell viability and decreasing the cell death rate and cleaved caspase-3 expression. NCAM-140 knockdown decreased cell viability and increased the cell death rate and cleaved caspase-3 expression, while its overexpression had the opposite effects. Notably, the amount of NCAM-140 located in lipid rafts increased after GDNF treatment. Pretreatment with 2-bromopalmitate, a specific inhibitor of protein palmitoylation, suppressed NCAM-140 translocation to lipid rafts and reduced the NCAM-mediated protective effects of GDNF on injured DA neuronal cells. Our results suggest that GDNF have the protective effects on injured DA cells by influencing NCAM-140 translocation into lipid rafts. PMID- 27003823 TI - Curcumin Rescues a PINK1 Knock Down SH-SY5Y Cellular Model of Parkinson's Disease from Mitochondrial Dysfunction and Cell Death. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra. Mutations in the PINK1 gene result in an autosomal recessive form of early-onset PD. PINK1 plays a vital role in mitochondrial quality control via the removal of dysfunctional mitochondria. The aim of the present study was to create a cellular model of PD using siRNA mediated knock down of PINK1 in SH-SY5Y neuroblastoma cells The possible protective effects of curcumin, known for its many beneficial properties including antioxidant and anti-inflammatory effects, was tested on this model in the presence and absence of paraquat, an additional stressor. PINK1 siRNA and control cells were separated into four treatment groups: (i) untreated, (ii) treated with paraquat, (iii) pre-treated with curcumin then treated with paraquat, or (iv) treated with curcumin. Various parameters of cellular and mitochondrial function were then measured. The PINK1 siRNA cells exhibited significantly decreased cell viability, mitochondrial membrane potential (MMP), mitochondrial respiration and ATP production, and increased apoptosis. Paraquat treated cells exhibited decreased cell viability, increased apoptosis, a more fragmented mitochondrial network and decreased MMP. Curcumin pre-treatment followed by paraquat exposure rescued cell viability and increased MMP and mitochondrial respiration in control cells, and significantly decreased apoptosis and increased MMP and maximal respiration in PINK1 siRNA cells. These results highlight a protective effect of curcumin against mitochondrial dysfunction and apoptosis in PINK1-deficient and paraquat-exposed cells. More studies are warranted to further elucidate the potential neuroprotective properties of curcumin. PMID- 27003824 TI - Oxygen transfer as a tool for fine-tuning recombinant protein production by Pichia pastoris under glyceraldehyde-3-phosphate dehydrogenase promoter. AB - Effects of oxygen transfer on recombinant protein production by Pichia pastoris under glyceraldehyde-3-phosphate dehydrogenase promoter were investigated. Recombinant glucose isomerase was chosen as the model protein. Two groups of oxygen transfer strategies were applied, one of which was based on constant oxygen transfer rate where aeration rate was Q O/V = 3 and 10 vvm, and agitation rate was N = 900 min(-1); while the other one was based on constant dissolved oxygen concentrations, C DO = 5, 10, 15, 20 and 40 % in the fermentation broth, by using predetermined exponential glucose feeding with MU o = 0.15 h(-1). The highest cell concentration was obtained as 44 g L(-1) at t = 9 h of the glucose fed-batch phase at C DO = 20 % operation while the highest volumetric and specific enzyme activities were obtained as 4440 U L(-1) and 126 U g(-1) cell, respectively at C DO = 15 % operation. Investigation of specific enzyme activities revealed that keeping C DO at 15 % was more advantageous with an expense of relatively higher by-product formation and lower specific cell growth rate. For this strategy, the highest oxygen transfer coefficient and oxygen uptake rate were K L a = 0.045 s(-1) and OUR = 8.91 mmol m(-3) s(-1), respectively. PMID- 27003825 TI - Potential of phosphoric acid-catalyzed pretreatment and subsequent enzymatic hydrolysis for biosugar production from Gracilaria verrucosa. AB - This study combined phosphoric acid-catalyzed pretreatment and enzymatic hydrolysis to produce biosugars from Gracilaria verrucosa as a potential renewable resource for bioenergy applications. We optimized phosphoric acid catalyzed pretreatment conditions to 1:10 solid-to-liquid ratio, 1.5 % phosphoric acid, 140 degrees C, and 60 min reaction time, producing a 32.52 +/- 0.06 % total reducing sugar (TRS) yield. By subsequent enzymatic hydrolysis, a 68.61 +/- 0.90 % TRS yield was achieved. These results demonstrate the potential of phosphoric acid to produce biosugars for biofuel and biochemical production applications. PMID- 27003826 TI - Restoration of growth by manganese in a mutant strain of Escherichia coli lacking most known iron and manganese uptake systems. AB - The interplay of manganese and iron homeostasis and oxidative stress in Escherichia coli can give important insights into survival of bacteria in the phagosome and under differing iron or manganese bioavailabilities. Here, we characterized a mutant strain devoid of all know iron/manganese-uptake systems relevant for growth in defined medium. Based on these results an exit strategy enabling the cell to cope with iron depletion and use of manganese as an alternative for iron could be shown. Such a strategy would also explain why E. coli harbors some iron- or manganese-dependent iso-enzymes such as superoxide dismutases or ribonucleotide reductases. The benefits for gaining a means for survival would be bought with the cost of less efficient metabolism as indicated in our experiments by lower cell densities with manganese than with iron. In addition, this strain was extremely sensitive to the metalloid gallium but this gallium toxicity can be alleviated by low concentrations of manganese. PMID- 27003827 TI - Medication safety research by observational study design. AB - Observational studies have been recognised to be essential for investigating the safety profile of medications. Numerous observational studies have been conducted on the platform of large population databases, which provide adequate sample size and follow-up length to detect infrequent and/or delayed clinical outcomes. Cohort and case-control are well-accepted traditional methodologies for hypothesis testing, while within-individual study designs are developing and evolving, addressing previous known methodological limitations to reduce confounding and bias. Respective examples of observational studies of different study designs using medical databases are shown. Methodology characteristics, study assumptions, strengths and weaknesses of each method are discussed in this review. PMID- 27003828 TI - Adherence with regulatory resolutions on prevention of NSAIDS-related gastrointestinal injury in Italy. AB - Background The rate of gastrointestinal (GI) complications with non-steroidal antiinflammatory drugs (NSAIDs) or low-dose aspirin (LD-ASA) varies according to risk factors. For at risk patients, the Italian regulatory resolution enforce prophylaxis with proton pump inhibitors (PPIs) or misoprostol. Objective This study evaluated the consistency with such resolution in patients receiving NSAIDs or LD-ASA and assessed whether patients continued to receive GI protection with PPIs for an adequate time following NSAID discontinuation. Setting An observational retrospective study was conducted using data from Health District of Pisa. Methods The analysis was performed on patients receiving prescription of NSAIDs or LD-ASA, with or without concomitant PPIs or misoprostol, accordingly with the presence of risk factors (2008-2010). Prescription data were retrieved from the database of reimbursement claims for dispensed drugs, while history of past GI diseases was obtained from primary or secondary discharge diagnosis. Main outcome measure The consistency rates of PPI and misoprostol prescriptions with Italian regulatory rules in patients receiving chronic NSAIDs or LD-ASA. Results 6869 patients, receiving NSAIDs or LD-ASA during the observation period, were eligible for the analysis. For NSAIDs or LD-ASA, gastroprotection rates in patients without risk factors were: 8 and 6 % in 2008; 10 and 8 % in 2009; 9 and 6 % in 2010; while the proportions of patients with one or more risk factors not receiving gastroprotection were: 12 and 17 % in 2008; 25 and 22 % in 2009; 15 and 17 % in 2010. In patients discontinuing chronic NSAIDs, 62 % were maintained on protection with PPIs, but only 28 % continued the PPI treatment for an adequate time (60 +/- 7 days). Conclusions The present analysis, although restricted to prescription patterns in a single health district, suggests scarce levels of consistency with Italian regulatory resolution on the prophylaxis of GI adverse events associated with chronic NSAIDs or LDASA. PMID- 27003829 TI - High levels of circulating TNFR1 increase the risk of all-cause mortality and progression of renal disease in type 2 diabetic nephropathy. AB - BACKGROUND: Several studies have demonstrated that levels of circulating inflammatory markers such as tumour necrosis factoralpha (TNFalpha), are associated with early progression of diabetic nephropathy (DN). The aim of this study was to investigate whether there is an association between circulating TNFalpha receptor and disease progression in patients with advanced type 2 DN and severe proteinuria. METHODS: Between 2006 and 2011, we measured levels of circulating soluble TNFalpha receptor 1 (TNFR1) and soluble TNFalpha receptor 2 (TNFR2) at baseline and 4 and 12 months in 101 patients included in a multicenter randomized controlled trial to compare the effect of optimal doses of renin angiotensin system blockers in monotherapy or in combination (dual blockade) to slow progression of established type 2 DN. The primary composite endpoint was a >50% increase in baseline serum creatinine, end-stage renal disease, or death. RESULTS: The median follow-up was 32 months (IQR, 18-48), during which time 28 patients (22.7%) achieved the primary endpoint. The TNFR1 level, but not the TNFR2 level, was correlated with other inflammatory markers. Cox regression analysis showed that the highest TNFR1 levels (HR, 2.60; 95%CI, 1.11-86.34) and baseline proteinuria (HR 1.32; 95%CI 1.15-1.52) were associated with the primary endpoint. The mixed model analysis revealed that TNFR1 and the TNFR2 levels did not change after starting treatment with renin-angiotensin system blockers. CONCLUSIONS: Our results show that the highest levels of TNFR1 are independently associated with progression of renal disease and death in type 2 DN. The renin angiotensin blockers have no effect on these inflammatory markers. PMID- 27003830 TI - Associations among family socioeconomic status, EEG power at birth, and cognitive skills during infancy. AB - Past research has demonstrated links between cortical activity, measured via EEG power, and cognitive processes during infancy. In a separate line of research, family socioeconomic status (SES) has been strongly associated with children's early cognitive development, with socioeconomic disparities emerging during the second year of life for both language and declarative memory skills. The present study examined associations among resting EEG power at birth, SES, and language and memory skills at 15-months in a sample of full-term infants. Results indicate no associations between SES and EEG power at birth. However, EEG power at birth was related to both language and memory outcomes at 15-months. Specifically, frontal power (24-48Hz) was positively correlated with later Visual Paired Comparison (VPC) memory scores. Power (24-35Hz) in the parietal region was positively correlated with later PLS-Auditory Comprehension language scores. These findings suggest that SES disparities in brain activity may not be apparent at birth, but measures of resting neonatal EEG power are correlated with later memory and language skills independently of SES. PMID- 27003831 TI - Does gender of the fetus have any relation with fetal heart monitoring during the first and second stage of labor? AB - OBJECTIVE: To investigate fetal gender and its influences on neonatal outcomes, taking into consideration the available tools for the assessment of fetal well being. METHODS: We conducted a retrospective study comparing maternal, fetal and neonatal outcomes according to fetal gender, in women carrying a singleton gestation. A multivariate analysis was performed for the prediction of adverse neonatal outcomes according to fetal gender, after adjustment for gestational age, maternal age and fetal weight. RESULTS: A total of 682 pregnancies were included in the study, of them 56% (n = 383) were carrying a male fetus and 44% (n = 299) a females fetus. Male gender was associated with a significant higher rate of abnormal fetal heart tracing patterns during the first (67.7% versus 55.1, p = 0.001) and the second stage (77.6 versus 67.7, p = 0.01) of labor. Male gender was also significantly associated with lower Apgar scores at 1' (19.1% versus 10.7%, p < 0.01), as well as lower pH values (7.18 +/- 0.15 versus 7.23 +/ 0.18, p < 0.001), and significant differences in cord blood components (PCO2, PO2) compared with female fetuses. In the multivariate analysis, male gender was found to be significantly associated with first (OR 1.76, 95% CI 1.28-2.43, p = 0.001) and second stage (OR 1.73, 95% CI 1.20-2.50, p < 0.01) pathological fetal heart tracing patterns, pH < 7.1, and for Apgar scores at 1'< 7. CONCLUSIONS: The present study confirms the general trend of a lower clinical performance of male neonates compared with females. In addition, the relation between fetal heart rate patterns during all stages of labor and fetal gender showed an independent association between male fetal gender and abnormal fetal heart monitoring during labor. PMID- 27003832 TI - Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine. AB - Two repurposed medications have been proposed to treat cocaine abuse. Progesterone, a gonadal hormone, and atomoxetine, a medication commonly used to treat attention deficit/hyperactivity disorder, have both been separately shown to reduce cocaine self-administration and reinstatement (i.e., relapse). The goal of the present study was to examine sex differences in the individual effects of PRO and ATO as well as the combination PRO+ATO treatment on cocaine (COC), caffeine (CAF), and/or cue-primed reinstatement of cocaine-seeking. Adult male and female Wistar rats lever-pressed under a FR 1 schedule for cocaine infusions (0.4mg/kg/inf). After 14 sessions of stable responding in daily 2-h sessions, rats underwent a 21-day extinction period when no drug or drug-related stimuli were present. Rats were then separated into four groups that received PRO (0.5mg/kg) alone (PRO+SAL), ATO (1.5mg/kg) alone (VEH+ATO), control (VEH+SAL) or combination (PRO+ATO) treatments prior to the reinstatement condition. Reinstatement of cocaine-seeking to cues and/or drug injections of cocaine or caffeine was tested after extinction. During maintenance, females self administered more cocaine than males, but no sex differences were seen during extinction. Females showed greater cocaine-seeking than males after a CAF priming injection. Individual treatment with ATO did not decrease reinstatement under any priming condition; however, the combination treatment decreased cocaine-seeking under the COC+CUES priming condition in males, and both PRO alone and the combination treatment decreased cocaine-seeking in the CAF+CUES condition in females. Overall, PRO alone was only effective in reducing reinstatement in females, while the combination treatment was consistently effective in reducing reinstatement in both sexes. PMID- 27003833 TI - The Effect of Polymeric Nanoparticles on Biocompatibility of Carrier Red Blood Cells. AB - Red blood cells (RBCs) can be used for vascular delivery of encapsulated or surface-bound drugs and carriers. Coupling to RBC prolongs circulation of nanoparticles (NP, 200 nm spheres, a conventional model of polymeric drug delivery carrier) enabling their transfer to the pulmonary vasculature without provoking overt RBC elimination. However, little is known about more subtle and potentially harmful effects of drugs and drug carriers on RBCs. Here we devised high-throughput in vitro assays to determine the sensitivity of loaded RBCs to osmotic stress and other damaging insults that they may encounter in vivo (e.g. mechanical, oxidative and complement insults). Sensitivity of these tests is inversely proportional to RBC concentration in suspension and our results suggest that mouse RBCs are more sensitive to damaging factors than human RBCs. Loading RBCs by NP at 1:50 ratio did not affect RBCs, while 10-50 fold higher NP load accentuated RBC damage by mechanical, osmotic and oxidative stress. This extensive loading of RBC by NP also leads to RBCs agglutination in buffer; however, addition of albumin diminished this effect. These results provide a template for analyses of the effects of diverse cargoes loaded on carrier RBCs and indicate that: i) RBCs can tolerate carriage of NP at doses providing loading of millions of nanoparticles per microliter of blood; ii) tests using protein free buffers and mouse RBCs may overestimate adversity that may be encountered in humans. PMID- 27003834 TI - A Regional Model for Malaria Vector Developmental Habitats Evaluated Using Explicit, Pond-Resolving Surface Hydrology Simulations. AB - Dynamical malaria models can relate precipitation to the availability of vector breeding sites using simple models of surface hydrology. Here, a revised scheme is developed for the VECTRI malaria model, which is evaluated alongside the default scheme using a two year simulation by HYDREMATS, a 10 metre resolution, village-scale model that explicitly simulates individual ponds. Despite the simplicity of the two VECTRI surface hydrology parametrization schemes, they can reproduce the sub-seasonal evolution of fractional water coverage. Calibration of the model parameters is required to simulate the mean pond fraction correctly. The default VECTRI model tended to overestimate water fraction in periods subject to light rainfall events and underestimate it during periods of intense rainfall. This systematic error was improved in the revised scheme by including the a parametrization for surface run-off, such that light rainfall below the initial abstraction threshold does not contribute to ponds. After calibration of the pond model, the VECTRI model was able to simulate vector densities that compared well to the detailed agent based model contained in HYDREMATS without further parameter adjustment. Substituting local rain-gauge data with satellite-retrieved precipitation gave a reasonable approximation, raising the prospects for regional malaria simulations even in data sparse regions. However, further improvements could be made if a method can be derived to calibrate the key hydrology parameters of the pond model in each grid cell location, possibly also incorporating slope and soil texture. PMID- 27003835 TI - Anti-IgE-assisted desensitization to egg and cow's milk in patients refractory to conventional oral immunotherapy. PMID- 27003836 TI - Biomechanical characteristics of pedicle screws in osteoporotic vertebrae comparing a new cadaver corpectomy model and pure pull-out testing. AB - Currently, evaluation of the stability of spinal instrumentations often focuses on simple pull-out or cyclic loading. However, the loading characteristics and the specimen alignment rarely simulate physiological loading conditions, or the clinical situation itself. The purpose of this study was to develop an alternative setup and parameters to compare static and dynamic characteristics of pedicle screws at the bone-implant interface in lumbar osteoporotic cadavers. A corpectomy model development was based on ASTM-1717 standard, allowing a deflection of the cranial and caudal element under loading. Twelve human osteoporotic vertebrae (L1-L4) were analyzed for morphological CT-data and T Score. For group A (n = 6) loads were simulated as in vivo measurements during walking, representing 2 months postoperatively. A subsequent pull-out was performed. Group B (n = 6) was tested with pure pull-out. Screw loosening at the tip/head was optically measured and analyzed with respect to clinical patterns. Correlations between CT-data, T-Score, and in vitro parameters were determined. For group A, the subsidence for the head/tip was measured towards the upper/lower endplate, resulting in visible deflections. The progress of the subsidence was greatest within the first and last cycles until failure. The predominant patterns were pure rotation and toggling. However, the pull-out between groups was not significantly different. Pedicle-angle and cyclic-subsidence correlated with R = 0.806/0.794. T-Score and pull-out correlated only in group A. With the corpectomy setup, clinically observed wipe effects and a loss of correction could be simulated. The presented parameters facilitate analysis of the complex changing load distributions and interactions between the left and right bone-implant interface. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:167-174, 2017. PMID- 27003837 TI - Does the Cave Environment Reduce Functional Diversity? AB - Caves are not colonised by all taxa present in the surface species pool, due to absence of light and the tendency to food limitation when compared to surface communities. Under strong species sorting during colonisation and later by the restrictive environmental filter, traits that are not adaptive in subterranean habitats may be filtered out. We tested whether cave communities were assembled by the restrictive regime propitiated by permanent darkness or by competitive exclusion due to resource scarcity. When compared to surface communities, the restrictive subterranean regime would lead to lower functional diversity and phenotypic clustering inside the caves, and the opposite should be expected in the case of competitive exclusion. Using isopods (Oniscidea) as model taxa, we measured several niche descriptors of taxa from surface and cave habitats, used a multivariate measure of functional diversity, and compared their widths. We found phenotypic overdispersion and higher functional diversity in cave taxa when compared to surface taxa. On the one hand, the dry climate outside of caves hampered the survival of several taxa and their ecological strategies, not viable under severe desiccation risk, culminating in the clustering of functional traits. In contrast, this restriction does not occur inside of caves, where isopods find favourable conditions under lower predation pressures and more amenable environmental parameters that allow occupation and subsequent diversification. Our results showed that, at least for some taxa, caves may not be such a harsh environment as previously thought. The high functional diversity we found inside caves adds an additional reason for the conservation of these sensitive environments. PMID- 27003838 TI - Surface morphology, tribological properties and in vitro biocompatibility of nanostructured zirconia thin films. AB - Deposition of nanostructured and low-wear zirconia (ZrO2) thin films on the metallic component of a total joint implant is envisaged to reduce wear of the soft ultra-high molecular weight polyethylene (UHMWPE) counterpart. In this work, morphological surface features, wear resistance and in vitro-biocompatibility of zirconia thin films deposited by the novel Pulsed Plasma Deposition (PPD) method have been investigated. Film thickness, roughness and wettability were found to be strongly dependent on deposition gas pressure. Interestingly, wear rate of UHMWPE disks coupled to zirconia-coated titanium spheres was only poorly correlated to the contact angle values, while film roughness and thickness seemed not to affect it. Furthermore, wear of UHMWPE, when coupled with zirconia coated titanium spheres, significantly decreased with respect to uncoated spheres under dry or NaCl-lubricated conditions; besides, when using bovine serum, similar results were obtained for coated and uncoated spheres. Finally, suitable mesenchymal stem and osteoblast cells adhesion, proliferation and viability were observed, suggesting good biocompatibility of the nanostructured zirconia films. Taken together, the results shown in this work indicate that zirconia thin films deposited by the PPD method deserve further investigations as low-wear materials for biomedical applications such as total joint replacement. PMID- 27003839 TI - Effect of silicate incorporation on in vivo responses of alpha-tricalcium phosphate ceramics. AB - In addition to calcium phosphate-based ceramics, glass-based materials have been utilized as bone substitutes, and silicate in these materials has been suggested to contribute to their ability to stimulate bone repair. In this study, a silicate-containing alpha-tricalcium phosphate (alpha-TCP) ceramic was prepared using a wet chemical process. Porous granules composed of silicate-containing alpha-TCP, for which the starting composition had a molar ratio of 0.05 for Si/(P + Si), and silicate-free alpha-TCP were prepared and evaluated in vivo. When implanted into bone defects that were created in rat femurs, alpha-TCP ceramics either with or without silicate were biodegraded, generating a hybrid tissue composed of residual ceramic granules and newly formed bone, which had a tissue architecture similar to physiological trabecular structures, and aided regeneration of the bone defects. Supplementation with silicate significantly promoted osteogenesis and delayed biodegradation of alpha-TCP. These results suggest that silicate-containing alpha-TCP is advantageous for initial skeletal fixation and wound regeneration in bone repair. PMID- 27003840 TI - Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity. AB - Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18-25) performed an emotion regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight. PMID- 27003841 TI - Bisphenol S Induces Adipogenesis in Primary Human Preadipocytes From Female Donors. AB - Human exposure to bisphenol A has been associated with negative health outcomes in humans and its use is now regulated in a number of countries. Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A; however, its effects on cellular metabolism and potential role as an endocrine disruptor have not been fully characterized. In the current study, we evaluated the effect of BPS on adipogenesis in primary human preadipocytes. The effect of BPS on the differentiation of human preadipocytes was determined after treatment with BPS at concentrations ranging from 0.1 nM to 25 MUM by quantifying lipid accumulation and mRNA and protein levels of key adipogenic markers. Treatment of preadipocytes with 25 MUM BPS induced lipid accumulation and increased the mRNA and protein levels of several adipogenic markers including lipoprotein lipase and adipocyte protein 2 (aP2). Cotreatment of cells with the estrogen receptor antagonist ICI 182,780 significantly inhibited BPS-induced lipid accumulation and affected aP2 but not lipoprotein lipase protein levels. Cotreatment of cells with the glucocorticoid receptor antagonist RU486 had no effect on BPS-induced lipid accumulation or protein levels. Furthermore, reporter gene assays using a synthetic promoter containing peroxisome proliferator-activated receptor-gamma (PPARG)-response elements and a PPARG-responsive human aP2 promoter region showed that BPS was able to activate PPARG. To our knowledge, this study is the first to show that BPS induces lipid accumulation and differentiation of primary human preadipocytes, and this effect may be mediated through a PPARG pathway. PMID- 27003842 TI - Perfluoroalkyl substances in older male anglers in Wisconsin. AB - BACKGROUND: Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and to dyslipidemia. The major source of PFAS exposure in the general population is seafood. OBJECTIVES: In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported health outcomes, in a group of older male anglers in Wisconsin with high fish consumption. METHODS: A biomonitoring study of male anglers aged 50 and older living in Wisconsin collected detailed information on fish consumption, demographics and self-reported health outcomes, along with hair and blood samples for biomarker analysis. Sixteen different PFAS were extracted from serum samples. Regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with PFAS biomarker levels in blood, as well as associations between PFAS and self-reported health outcomes, adjusting for potential confounders. RESULTS: Seven PFAS were detected in at least 30% of participants and were used in subsequent analyses (PFDA, PFHpS, PFHxS, PFNA, PFOA, PFOS, PFuDA). The PFAS with the highest levels were PFOS, followed by PFOA, PFHxS and PFNA (medians of 19.0, 2.5, 1.8 and 1.4ng/mL). In general, increasing age was associated with higher PFAS levels, while increasing BMI were associated with lower PFAS levels. Greater alcohol consumption was associated with higher levels of PFHpS, PFHxS and PFOA. Associations with smoking and employment did not show a consistent pattern. Associations between fish consumption and PFAS were generally weak, with the exception of notably higher PFDA and PFHpS with both other locally-caught fish, and restaurant-purchased fish. Regarding associations with health outcomes, PFuDA, PFNA and PFDA were all associated with increased risk of pre-diabetes and/or diabetes. PFHpS was associated with a significantly increased risk of high cholesterol; PFDA and PFuDA also showed notable, though non-significant associations. All PFAS evaluated were associated with lower risk of hypertension although the only significant odds ratio was that for PFNA. There were no associations between any of the PFAS examined and either coronary heart disease, or the grouped outcome of any cardiovascular condition. CONCLUSIONS: PFAS are emerging contaminants with widespread exposure, persistence, and potential for adverse health effects. In this study population, demographic patterns may reflect differences in exposure sources, or possibly differences in adsorption and metabolism. PFAS were associated mainly with endocrine related outcomes, with a general trend towards increased risk of glucose intolerance and high cholesterol. Continued research on the risks and benefits of fish consumption is important due to potential exposure to PFAS and noted associations with highly prevalent adverse health outcomes. PMID- 27003843 TI - Tourette's syndrome and associated disorders: a systematic review. AB - OBJECTIVE: To compile data on Tourette's syndrome (TS), tics and associated disorders. METHODS: A systematic review of the literature was conducted using the 5S levels of organization of healthcare research evidence (systems, summaries, synopses, syntheses, studies), based on the model described by Haynes. The search keywords were Tourette, tics and comorbidity, which were cross-referenced. Studies provided by publishers and articles being processed on July 31, 2013, were also included. RESULTS: Of all studies retrieved during the search, 64 were selected because they analyzed the epidemiology, clinical features and etiopathogenesis of TS and its comorbidities. TS is classified as a hyperkinetic movement disorder, and at least 90% of the patients have neuropsychiatric comorbidities, of which attention deficit hyperactivity and obsessive-compulsive disorders are the most common. The syndrome is clinically heterogeneous and has been associated with a dysfunction of cortico-striatal-thalamic-cortical circuits involving various neurotransmitters. Although its genetic etiology has been widely studied, other factors may be important to understand this syndrome and its associated disorders. CONCLUSIONS: TS is a neurodevelopmental disorder that results from the impact of stress factors on a vulnerable biological substrate during the critical periods of neurodevelopment. The study of TS and its comorbidities may contribute, at different levels, to the understanding of several neuropsychiatric disorders of clinical and therapeutic relevance. PMID- 27003844 TI - Impact of physical exercise on quality of life of older adults with depression or Alzheimer's disease: a systematic review. AB - INTRODUCTION: Physical exercise has been associated with improvement of quality of live (QoL), but its effect among the elderly with depression and Alzheimer's disease (AD) is still unclear. This systematic review evaluated randomized and controlled studies about the effect of physical exercise on QoL of older individuals with a clinical diagnosis of depression and AD. METHODS: We searched PubMed, ISI, SciELO and Scopus from December 2011 to June 2013 using the following keywords: physical exercise, quality of life, elderly, depression, Alzheimer's disease. Only six studies met inclusion criteria: two examined patients with AD and four, patients with depression. RESULTS: The studies used different methods to prescribe exercise and evaluate QoL, but all had high quality methods. Findings of most studies with individuals with depression suggested that exercise training improved QoL, but studies with patients with AD had divergent results. CONCLUSIONS: Although different methods were used, results suggested that physical exercise is an effective non-pharmacological intervention to improve the QoL of elderly individuals with depression and AD. Future studies should investigate the effect of other factors, such as the use of specific scales for the elderly, controlled exercise prescriptions and type of control groups. PMID- 27003845 TI - Weight regain among women after metabolic and bariatric surgery: a qualitative study in Brazil. AB - INTRODUCTION: Due to the increased number of bariatric surgeries over the years, aspects contributing or hindering the achievement of outcomes, among them weight regain, have acquired increased significance. Psychological factors directly influence on this unwanted situation, but there are few studies and controversies about the degree of participation of these factors. We propose a qualitative investigation to analyze the meanings of weight regain after surgery among women and how these factors influence this outcome. METHOD: This study uses the clinical-qualitative method, by means of a semi-structured interview with open questions in an intentional sample, closed by saturation, with eight women who underwent surgery at the Bariatric Surgery Outpatient Clinic of Hospital das Clinicas, Universidade Estadual de Campinas (UNICAMP), in the state of Sao Paulo, Brazil. RESULTS: A feeling of defeat and failure emerges with weight regain, which contributes to social isolation; there is no regret, but gratitude for the surgery; among patients, there is a sense of feeling rejected greater than a rejection that actually exists. CONCLUSION: We found out the need for further qualitative studies that help the health team to better understand the dynamic psychological factors involved in the meaning of weight regain after bariatric surgery among women, in order to adopt appropriate conducts to deal with this problem. PMID- 27003846 TI - Dysfunctional family environments and childhood psychopathology: the role of psychiatric comorbidity. AB - INTRODUCTION: The study of the association between specific characteristics of family environments and different types of psychopathology may contribute to our understanding of these complex disorders and ultimately inform therapeutics. OBJECTIVE: To compare the family characteristics of four groups: typically developing children; children with anxiety disorders only; children with externalizing disorders only; and children with both anxiety and externalizing disorders. METHODS: This study enrolled 115 individuals from the community. Child psychiatrists made psychiatric diagnoses using a structured clinical interview. The Family Environment scale was used to evaluate six domains of family function. RESULTS: The group with both anxiety and externalizing disorders had higher levels of conflict in family environment and lower levels of organization when compared with typically developing children. In addition, internalizing and externalizing symptoms were positively associated with conflict and negatively with organization. Maternal depressive and anxious symptoms were also associated with higher conflict and lower organization scores. CONCLUSION: An important between-group difference in comorbid cases of anxiety and behavioral disorders suggests that children with this comorbidity are potential candidates for family interventions to address family conflicts and organizational aspects. PMID- 27003847 TI - Aggressive behavior during the first 24 hours of psychiatric admission. AB - OBJECTIVE: To investigate the association between aggression in the first 24 hours after admission and severity of psychopathology in psychiatric inpatients. METHODS: This cross-sectional study included psychiatric patients admitted to Hospital Universitario de Santa Maria, in Santa Maria, southern Brazil, from August 2012 to January 2013. At their arrival at the hospital, patients were interviewed to fill in the Brief Psychiatric Rating Scale (BPRS) form, and any aggressive episodes in the first 24 hours after admission were recorded using the Overt Aggression Scale (OAS). The Mann-Whitney U test was used to compare patients according to aggressiveness: aggressive versus non-aggressive, hostile versus violent, and aggressive against others only versus self-aggressive. RESULTS: The sample was composed of 110 patients. Aggressive patients in general had higher BPRS total scores (p = 0.002) and individual component scores, and their results showed more activation (p < 0.001) and thinking disorders (p = 0.009), but less anxious-depression (p = 0.008). Violent patients had more severe psychomotor agitation (p = 0.027), hallucinations (p = 0.017) and unusual thought content (p = 0.020). Additionally, self-aggressive patients had more disorientation (p = 0.011) and conceptual disorganization (p = 0.007). CONCLUSIONS: Aggression in psychiatric patients in the first 24 hours after admission is associated with severity of psychopathology, and severity increases with severity of patient psychosis and agitation. PMID- 27003848 TI - Measures of cognitive reserve in Alzheimer's disease. AB - INTRODUCTION: Cognitive reserve (CR), a hypothetical construct used to obtain information about cognitive aging, describes the capacity of the adult brain to cope with the effects of neurodegenerative processes. This study evaluated CR using a CR questionnaire (CRQ) and a set of variables (education, leisure activities, lifelong occupation) that inform CR. It also developed a CR index, validated the CRQ, and examined the correlation between the different CR measures. METHODS: Functional and neuropsychological capacities of 75 outpatients (mean age: 80.2 years) with a probable AD diagnosis were evaluated. Socio demographic data and clinical variables were collected. Patients completed two questionnaires: the Participation in Leisure Activities throughout Life questionnaire, and the CRQ. RESULTS: Participants with a greater CR had higher scores in cognitive tests than the elderly with a lower CR. A CR index was developed. CRQ reliability was 0.795 (Cronbach's alpha). There was a close association between the CR Index and the CRQ. CONCLUSIONS: This study found an association between CR measures and education, occupation and participation in leisure activities. The CRQ seems to be a suitable instrument to measure CR in Portuguese populations. PMID- 27003849 TI - Profile of patients treated with malariotherapy in a psychiatric hospital in Porto Alegre, Brazil: a historical note. AB - INTRODUCTION: Malariotherapy was a treatment to cure neurosyphilis developed in 1917 by Wagner-Jauregg, by inoculating blood infected with malaria in patients with neurosyphilis. The patient had febrile episodes that often cured him of the syphilitic infection. This treatment won the Nobel Prize in Medicine in 1927 and it was introduced in Hospital Psiquiatrico Sao Pedro (HPSP) in 1929. METHODS: This is a descriptive retrospective cross-sectional study with collection of historical secondary data. Data were collected from a sample of 19 medical records of patients treated with malariotherapy in HPSP, in 1929 and 1930. RESULTS: Most patients were white men aged from 25 to 40 years. The mean length of hospital stay was 1.4 year and the outcomes at this early application of malariotherapy were mostly negative (63.2% died). DISCUSSION: The 19 cases evaluated in this study refer to the first year of application of malariotherapy in HPSP. The statistics available on the total number of dead and cured people over the 10 years this therapy was deployed suggest that the outcomes were better in the subsequent years, possibly due to improvement of technique. As a consequence of this innovative research, which had as its principle reorganizing the central nervous system by using the seizure triggered by malaria fever, other forms of shock therapies were developed, such as insulin therapy, cardiazol shock therapy, and electroconvulsive therapy. PMID- 27003850 TI - Occurrence of and Risk Factors for Ocular Hypertension and Secondary Glaucoma in Juvenile Idiopathic Arthritis-associated Uveitis. AB - PURPOSE: To describe the incidence of ocular hypertension (OHT) and secondary glaucoma (SG) in JIA-associated uveitis, identify risk factors for development of these complications, and describe their effect on visual outcomes. METHODS: A retrospective cohort of 108 patients (196 eyes) with JIA-associated uveitis seen over 30 years at an academic practice. RESULTS: Of examined eyes, 40% had OHT or SG at presentation. These eyes had a nearly three-fold higher incidence of legal blindness during follow-up, compared with eyes without OHT or SG. An additional 41 eyes developed OHT or SG during follow-up. Presenting with anterior uveitis, active inflammation, and using systemic corticosteroids were risk factors for developing OHT, while use of immunosuppressive medication at presentation reduced this risk. Risk factors for developing SG included anterior uveitis and use of systemic corticosteroids. CONCLUSIONS: OHT and SG were common in patients with JIA-associated uveitis. Use of immunosuppressive drugs may decrease the risk of developing OHT. PMID- 27003851 TI - The Cancer Conundrum: How should transplant professionals manage their patients in the era of cancer immunotherapy? PMID- 27003854 TI - Fatal Complication of Recent Liver Transplant. PMID- 27003855 TI - Erratum. PMID- 27003857 TI - The electronic structure, mechanical flexibility and carrier mobility of black arsenic-phosphorus monolayers: a first principles study. AB - New artificial layered semiconductors - black arsenic-phosphorus (b-AsP) - which have tunable band gaps owing to good tunability of the chemical compositions have been synthesized in a recent experiment. In the present work, first principles calculations are performed to systematically study the structure, and mechanical, electrical, and transport properties of b-AsP monolayers. The mechanical analysis demonstrates that the exfoliation of single-layer b-AsP systems from the bulk form is more difficult compared with that of pure black phosphorus (BP). In addition, the breaking strain of the b-AsP monolayer is comparable with other widely studied two dimensional materials, indicating their excellent mechanical flexibility and good potential for flexible device applications. Besides, the electronic structures of b-AsP system monolayers are not sensitive to their specific compositions, which however, can be flexibly modulated by the strain effect. The predicted carrier mobilities of b-AsP systems are directionally anisotropic, similar to pure BP. However, the degradation of their carrier mobilities may become a practical limitation in real electronic device applications. PMID- 27003856 TI - Outcomes of Seropositive Patients With Marsh 1 Histology in Clinical Practice. AB - GOALS: We retrospectively studied all seropositive Marsh 1 patients seen at 2 tertiary care hospitals in the last 15 years to determine their clinical, serological, and histologic outcomes. BACKGROUND: Patients with positive celiac serologies and Marsh 1 histology represent an understudied subgroup of patients, and it is unclear whether they should be advised to adopt a gluten-free diet (GFD). STUDY: Subjects were identified based on positive celiac serologies and Marsh 1 histology while on a full-gluten diet. Clinical presentation and baseline laboratory data were noted. Clinical course, repeat serologies, and histology were determined. RESULTS: Of 620 patients with positive celiac serologies and abnormal duodenal histology, we identified 36 (5.8%) with positive tissue transglutaminase and/or antiendomysial antibodies and Marsh 1 lesions who had adequate follow-up. Abdominal pain was the commonest (47.2%) presenting symptom. Twenty-eight patients were advised to adopt GFD, whereas 8 were not. Among patients treated with GFD, 88.9% improved symptomatically and 95% normalized serology. In contrast, among patients who continued to consume gluten, 85.7% remained symptomatic and 80% had persistently positive serologies. Among the 8 patients on normal diet, 5 underwent repeat biopsy, and 4 of them had the same or worse histology, with 3 patients progressing to Marsh 3c. Among the 28 patients on GFD, 5 underwent repeat biopsy and all improved to normal histology. CONCLUSIONS: Most patients with positive celiac serology and Marsh 1 lesions benefit from GFD and, if not treated, a majority will continue to be symptomatic and remain at risk of progressing to villous atrophy. PMID- 27003858 TI - Cinnamomum camphora Seed Kernel Oil Ameliorates Oxidative Stress and Inflammation in Diet-Induced Obese Rats. AB - Cinnamomum camphora seed kernel oil (CCSKO) was found to reduce body fat deposition and improve blood lipid in both healthy and obese rats. The study was aimed to investigate the antioxidative stress and anti-inflammatory effects of CCSKO in high-fat-diet-induced obese rats. The obese rats were treated with CCSKO, lard, and soybean oil, respectively, for 12 wk. The level of total antioxidant capacity (T-AOC), activities of superoxide dismutase (SOD), glutathione peroxidase, and catalase, and levels of malondialdehyde (MDA), tumor necrosis factor (TNF)-alpha, peroxisome proliferator-activated receptor (PPAR) gamma, interleukin (IL)-6, and P65 were compared among CCSKO, lard, and soybean oil groups. Our results showed that the level of T-AOC and activities of SOD and catalase were significantly increased and the level of MDA was significantly decreased in CCSKO group. In addition, CCSKO treatment reduced the activities of serum glutamic oxaloacetic transaminase and glutamate-pyruvate transaminase, and levels of serum TNF-alpha, IL-6, and P65 through raising the level of PPAR-gamma. In conclusion, CCSKO has, for the first time, been found to ameliorate oxidative stress and inflammation in high-fat-diet-induced obese rats. PMID- 27003859 TI - [Recruitment of osteogenic cells to bone formation sites during development and fracture repair - German Version]. AB - Recruitment of osteoblast lineage cells to their bone-forming locations is essential for skeletal development and fracture healing. In developing bones, osteoprogenitor cells invade the cartilage mold to establish the primary ossification center. Similarly, osteogenic cells infiltrate and populate the callus tissue that is formed following an injury. Proper bone development and successful fracture repair must, therefore, rely on controlled temporal and spatial navigation cues guiding the cells to the sites where new bone formation is needed. Some cellular mechanisms and molecular pathways involved have been elucidated. PMID- 27003861 TI - [International quality indicators in rheumatology. Suggestions for rheumatoid arthritis]. AB - Quality measurement of medical care has become increasingly important in Germany in recent years. Essentially, three areas can be distinguished: the quality of structure, process and outcome. For the measurement of quality, quality indicators are necessary. The Federal Joint Committee has recently been responsible for defining such quality indicators. Because proposals for quality indicators for the indication for rheumatoid arthritis in have already been published in international rheumatology, we selected and translated the three most important European publications in order to present them to the rheumatology community. The ultimate aim is the initiation of a process for the joint development of quality indicators within the professional association and the two associations in Germany in order to then be able to adequately discuss these with policy-makers. PMID- 27003863 TI - Distribution of facial injuries in cases involving a fall on a flat surface. AB - AIM OF THE STUDY: Determination whether injuries identified on the victim's head were caused by a blow made by another person or by a fall resulting in hitting a surface. MATERIAL AND METHODS: An analysis of archive photographs taken routinely at the Forensic Institute in Krakow, Poland, to document post-mortem examinations in the years 2004-2012. RESULTS: A comparative analysis of the images clearly shows that certain areas are much more vulnerable to contact with the surface and thus to injuries; other areas are clearly protected in the case of a fall on a flat surface. CONCLUSIONS: In the case of a fall on a solid, flat surface, injuries are located first of all on brow ridges, nasal bridge and nasal apex, on the malar area and on the front surface of the chin. The following areas are clearly protected: eyelids, eyebrows, medial and upper parts of the cheeks, lips and the lower part of the chin. PMID- 27003862 TI - AstRoMap European Astrobiology Roadmap. AB - The European AstRoMap project (supported by the European Commission Seventh Framework Programme) surveyed the state of the art of astrobiology in Europe and beyond and produced the first European roadmap for astrobiology research. In the context of this roadmap, astrobiology is understood as the study of the origin, evolution, and distribution of life in the context of cosmic evolution; this includes habitability in the Solar System and beyond. The AstRoMap Roadmap identifies five research topics, specifies several key scientific objectives for each topic, and suggests ways to achieve all the objectives. The five AstRoMap Research Topics are * Research Topic 1: Origin and Evolution of Planetary Systems * Research Topic 2: Origins of Organic Compounds in Space * Research Topic 3: Rock-Water-Carbon Interactions, Organic Synthesis on Earth, and Steps to Life * Research Topic 4: Life and Habitability * Research Topic 5: Biosignatures as Facilitating Life Detection It is strongly recommended that steps be taken towards the definition and implementation of a European Astrobiology Platform (or Institute) to streamline and optimize the scientific return by using a coordinated infrastructure and funding system. PMID- 27003864 TI - Searching for new features of intravitality of hanging based on macro- and microscopic evaluation of the proximal attachment of the sternocleidomastoid muscle and the mastoid process of the temporal bone. AB - AIM OF THE STUDY: Assessment of the usefulness of intravital lesions in the proximal attachment of the sternocleidomastoid muscle and the mastoid process of the temporal bone in medico-legal evaluation of death by hanging. MATERIAL AND METHODS: The study material was obtained from the bodies of 35 people who died by hanging. The control group comprised specimens collected from 30 people who died of non-traumatic causes. The structures under study were examined macro- and microscopically. The basic change which could be recognized as a marker of intravitality of hanging was the presence of a macroscopically extensive blotchy area of abundant ecchymosis in the proximal muscle attachment, similar to that found in the distal attachment, and the presence of abundant diffuse intraosseous ecchymoses in the mastoid process. RESULTS: None of the cases revealed any ecchymoses in the proximal attachment of the muscle that would be similar to those present in the distal attachment. Discolourations within the mastoid processes, macroscopically suggestive of extensive intraosseous effusions arising from the mechanism of stretching, were not confirmed by microscopic evaluation and occurred at the same frequency as in the control group. Limitations of the study were related to the method which involved sample collection by means of bone chisels, decalcification and preparation of specimens, which had an effect, for example, on the measurable evaluation of the degree of congestion. CONCLUSIONS: The study has failed to provide convincing and unambiguous data on the usefulness of examining mastoid processes and proximal attachments of the sternocleidomastoid muscles during autopsy to determine the presence of intravitality features of hanging. A description of research methodology and its associated difficulties, e.g. with the interpretation of results, can also be useful for the planning of similar studies by other researchers. PMID- 27003865 TI - Clinical and analytical problems of sodium azide poisonings as exemplified by a case of fatal suicidal poisoning. AB - AIM OF THE STUDY: To present clinical and analytical aspects associated with sodium azide poisoning. The problems were verified on the basis of a case of sodium azide poisoning which was unique due to its circumstances and the development of an analytical method applied for medico-legal practice. MATERIAL AND METHODS: The object of the study was a toxicological analysis of biological specimens collected from a woman who ingested two doses of sodium azide purchased over the Internet, in a suicide attempt. After the ingestion of the first dose, the clinical management in the form of symptomatic treatment indicated a possibility of recovery. However, the ingestion of a second dose of the xenobiotic, already in the hospital, caused death. Toxicological findings were obtained with the dedicated technique of gas chromatography-mass spectrometry (GC EI-MS-MS) after extraction combined with derivatization using pentafluorobenzyl bromide (PFBBr). RESULTS: Post-mortem toxicological studies demonstrated sodium azide in the blood (0.18 mg/l) and urine (6.50 mg/l) samples collected from the woman. CONCLUSIONS: Cases of sodium azide poisoning are rare and difficult to treat, but a review of the literature over a longer interval of time shows that they continue to occur. Therefore, case studies of sodium azide poisoning, together with descriptions of research methodology, can be useful both in clinical terms and in the preparation of toxicological expert opinions for medico legal purposes. PMID- 27003866 TI - Complications of aesthetic medicine procedures: five case studies. AB - The paper presents the cases of five patients who developed complications after aesthetic medicine procedures. Four of the cases involved women who reported to the Department of Forensic Medicine, Medical University of Lodz, for a description and legal qualification of bodily injuries suffered as a result of aesthetic medicine procedures, whereas one was related to the assessment of accuracy of medical management at the request of the prosecutor handling the case. The reported cases concerned acid exfoliation treatments, photoepilation and cryotherapy. The authors attempt to discuss the most common complications that may occur after aesthetic medicine procedures, and measures to avoid them. PMID- 27003867 TI - Amphetamine-related myocardial infarction in a 42-year old man. AB - Myocardial infarction is an infrequent condition in young adults. In most cases, it occurs due to causes other than atherosclerosis of the coronary arteries, including blood hypercoagulability, congenital anomalies of the coronary arteries, their inflammation or spasm induced by amphetamine or cocaine use. Amphetamine and its derivatives, via increasing the levels of epinephrine, serotonin and dopamine in the central nervous system, exert their effect also on the cardiovascular system, causing coronary spasm, enhancing platelet aggregation and inducing tachyarrhythmias. The paper presents a case of a 42-year-old man admitted to the emergency department because of emaciation and dehydration. The man was conscious, without contact, with a significant elevation of body temperature and tachycardia. On the basis of examinations, a fresh infarction of the anterolateral wall of the heart was diagnosed and the patient was transferred to a cardiac intensive care unit. There, laboratory tests revealed significantly elevated markers of myocardial necrosis and the presence of amphetamine in blood and urine. In spite of the institution of treatment the patient developed cardiorespiratory arrest. Advanced resuscitation procedures were undertaken, however, they proved unsuccessful. The presence of an infarction focus was confirmed in autopsy. Toxicological analysis of the blood for the presence of alcohol-like substances detected amphetamine at a concentration of 269.5 ng/ml. After examining the complete body of evidence it was established that the patient had died of acute cardiorespiratory failure secondary to an extensive fresh myocardial infarction. As indicated by the accumulated data, the most probable cause of myocardial infarction was amphetamine poisoning. PMID- 27003868 TI - Chylothorax as a rare complication of acute pancreatitis in a 25-year-old woman after cesarean section. AB - The paper presents the case of a 25-year-old woman who underwent cesarean section for gynecological indications in the 37(th) week of her second pregnancy. The perioperative course was uncomplicated, but one day later the general condition of the patient suddenly deteriorated: she developed respiratory disorders requiring intubation and treatment in an intensive care unit. On the 6(th) day after the surgery, the patient was diagnosed with acute pancreatitis. Appropriate conservative treatment was instituted, resulting in a gradual improvement of her condition. On the 13(th) postoperative day, a cardiac arrest in asystole occurred, with no response to the undertaken resuscitation procedures. An autopsy performed in the Department of Forensic Medicine in Lodz revealed, among other findings, acute pancreatitis with enzymatic necrosis of the adipose tissue, a significant accumulation of lymph in both pleural cavities, and pulmonary atelectasis. As demonstrated by the analysis of the case, chylothorax had most probably developed in the course of acute pancreatitis which was a complication of the cesarean section. Consequently, the prosecutor opened an investigation into the case under Article 155 of the Polish Penal Code to assess the appropriateness of medical management. The medico-legal opinion was issued by experts from outside the Department of Forensic Medicine in Lodz. In their view, the medical management of the patient was correct. PMID- 27003869 TI - Understanding and utilizing crop genome diversity via high-resolution genotyping. AB - High-resolution genome analysis technologies provide an unprecedented level of insight into structural diversity across crop genomes. Low-cost discovery of sequence variation has become accessible for all crops since the development of next-generation DNA sequencing technologies, using diverse methods ranging from genome-scale resequencing or skim sequencing, reduced-representation genotyping by-sequencing, transcriptome sequencing or sequence capture approaches. High density, high-throughput genotyping arrays generated using the resulting sequence data are today available for the assessment of genomewide single nucleotide polymorphisms in all major crop species. Besides their application in genetic mapping or genomewide association studies for dissection of complex agronomic traits, high-density genotyping arrays are highly suitable for genomic selection strategies. They also enable description of crop diversity at an unprecedented chromosome-scale resolution. Application of population genetics parameters to genomewide diversity data sets enables dissection of linkage disequilibrium to characterize loci underlying selective sweeps. High-throughput genotyping platforms simultaneously open the way for targeted diversity enrichment, allowing rejuvenation of low-diversity chromosome regions in strongly selected breeding pools to potentially reverse the influence of linkage drag. Numerous recent examples are presented which demonstrate the power of next-generation genomics for high-resolution analysis of crop diversity on a subgenomic and chromosomal scale. Such studies give deep insight into the history of crop evolution and selection, while simultaneously identifying novel diversity to improve yield and heterosis. PMID- 27003870 TI - Erratum. PMID- 27003871 TI - Immunoassay for tumor markers in human serum based on Si nanoparticles and SiC@Ag SERS-active substrate. AB - Based on a sandwich structure consisting of nano-Si immune probes and a SiC@Ag SERS-active immune substrate, a kind of ultra-sensitive immunoassay protocol is presented to detect tumor markers in human serum. The nano-Si immune probes were prepared by immobilizing the detecting antibodies onto the surfaces of SiO2 coated Si nanoparticles (NPs) which were modified with 3 (aminopropyl)trimethoxysilane, and the SiC@Ag SERS-active immune substrates were prepared by immobilizing the captured antibodies on Ag film sputtered on SiC sandpaper. To the best of our knowledge, it is the first time that Si NPs are directly used as Raman tags in an immunoassay strategy. And, the SiC@Ag SERS active substrates exhibit excellent surface enhanced Raman scattering (SERS) performances with an enhancement factor of ~10(5), owing to the plasmonic effect of the Ag film on the rough surface of the SiC sandpaper. In our experiments, the sandwich immunoassay structure has been successfully applied to detect prostate specific antigen (PSA), alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) in a human serum sample and the limit of detections are as low as 1.79 fg mL(-1), 0.46 fg mL(-1) and 1.3 * 10(-3) U mL(-1), respectively. It reveals that the proposed immunoassay protocol has demonstrated a high sensitivity for tumor markers in human serum and a potential practicability in biosensing and clinical diagnostics. PMID- 27003872 TI - Effect of Root Moisture Content and Diameter on Root Tensile Properties. AB - The stabilization of slopes by vegetation has been a topical issue for many years. Root mechanical characteristics significantly influence soil reinforcement; therefore it is necessary to research into the indicators of root tensile properties. In this study, we explored the influence of root moisture content on tensile resistance and strength with different root diameters and for different tree species. Betula platyphylla, Quercus mongolica, Pinus tabulaeformis, and Larix gmelinii, the most popular tree species used for slope stabilization in the rocky mountainous areas of northern China, were used in this study. A tensile test was conducted after root samples were grouped by diameter and moisture content. The results showedthat:1) root moisture content had a significant influence on tensile properties; 2) slightly loss of root moisture content could enhance tensile strength, but too much loss of water resulted in weaker capacity for root elongation, and consequently reduced tensile strength; 3) root diameter had a strong positive correlation with tensile resistance; and4) the roots of Betula platyphylla had the best tensile properties when both diameter and moisture content being controlled. These findings improve our understanding of root tensile properties with root size and moisture, and could be useful for slope stabilization using vegetation. PMID- 27003873 TI - A new family of insect muscarinic acetylcholine receptors. AB - Most currently used insecticides are neurotoxic chemicals that target a limited number of sites and insect cholinergic neurotransmission is the major target. A potential target for insecticide development is the muscarinic acetylcholine receptor (mAChR), which is a metabotropic G-protein-coupled receptor. Insects have A- and B-type mAChRs and the five mammalian mAChRs are close to the A-type. We isolated a cDNA (CG12796) from the fruit fly, Drosophila melanogaster. After heterologous expression in Chinese hamster ovary K1 cells, CG12796 could be activated by acetylcholine [EC50 (half maximal effective concentration), 73 nM] and the mAChR agonist oxotremorine M (EC50 , 48.2 nM) to increase intracellular Ca(2+) levels. Thus, the new mAChR is coupled to Gq/11 but not Gs and Gi/o . The classical mAChR antagonists atropine and scopolamine N-butylbromide at 100 MUM completely blocked the acetylcholine-induced responses. The orthologues of CG12796 can also be found in the genomes of other insects, but not in the genomes of the honeybee or parasitoid wasps. Knockdown of CG12796 in the central nervous system had no effect on male courtship behaviours. We suggest that CG12796 represents the first recognized member of a novel mAChR class. PMID- 27003874 TI - Amblyopia Associated with Congenital Facial Nerve Paralysis. AB - The association between congenital facial paralysis and visual development has not been thoroughly studied. Of 27 pediatric cases of congenital facial paralysis, we identified 3 patients who developed amblyopia, a visual acuity decrease caused by abnormal visual development, as comorbidity. These 3 patients had facial paralysis in the periocular region and developed amblyopia on the paralyzed side. They started treatment by wearing an eye patch immediately after diagnosis and before the critical visual developmental period; all patients responded to the treatment. Our findings suggest that the incidence of amblyopia in the cases of congenital facial paralysis, particularly the paralysis in the periocular region, is higher than that in the general pediatric population. Interestingly, 2 of the 3 patients developed anisometropic amblyopia due to the hyperopia of the affected eye, implying that the periocular facial paralysis may have affected the refraction of the eye through yet unspecified mechanisms. Therefore, the physicians who manage facial paralysis should keep this pathology in mind, and when they see pediatric patients with congenital facial paralysis involving the periocular region, they should consult an ophthalmologist as soon as possible. PMID- 27003875 TI - Tips for laparoscopic pancreaticoduodenectomy. AB - Highlight Despite its advantages, laparoscopic pancreaticoduodenectomy remains limited to a few selected centers, due to its complexity and steep learning curve. In this technical view, Asbun and colleagues share their expertise and describe in detail their conventional technique for laparoscopic pancreaticoduodenectomy to facilitate the adoption of this procedure at other centers. PMID- 27003876 TI - Decline of cell viability and mitochondrial activity in mouse skeletal muscle cell in a hypomagnetic field. AB - Hypomagnetic field (HMF), one of the key environmental risk factors for astronauts traveling in outer space, has previously been shown to repress locomotion of mammalians. However, underlying mechanisms of how HMF affects the motor system remains poorly understood. In this study, we created an HMF (<3 MUT) by eliminating geomagnetic field (GMF, ~50 MUT) and exposed primary mouse skeletal muscle cells to this low magnetic field condition for a period of three days. HMF-exposed cells showed a decline in cell viability relative to GMF control, even though cells appeared normal in terms of morphology and survival rate. After a 3-day HMF-exposure, glucose consumption of skeletal muscle cells was significantly lower than GMF control, accompanied by less adenosine triphosphate (ATP) and adenosine diphosphate (ADP) content and higher ADP/ATP ratio. In agreement with these findings, mitochondrial membrane potential of HMF exposed cells was also lower, whereas levels of cellular Reactive Oxygen Species were higher. Moreover, viability and membrane potential of isolated mitochondria were reduced after 1 h HMF-exposure in vitro. Our results indicate that mitochondria can directly respond to HMF at functional level, and suggest that HMF-induced decline in cell functionality results from a reduction in energy production and mitochondrial activity. PMID- 27003877 TI - Myocardial substrate after cardiac resynchronization therapy and the risk of ventricular arrhythmias. PMID- 27003878 TI - Magnetic Resonance Imaging of Pituitary Tumors. AB - Magnetic Resonance Imaging (MRI) is currently considered a major keystone of the diagnosis of diseases of the hypothalamic-hypophyseal region. However, the relatively small size of the pituitary gland, its location deep at the skull base and the numerous physiological variants present in this area impede the precise assessment of the anatomical structures and, particularly, of the pituitary gland itself. The diagnosis of the often tiny lesions of this region--such as pituitary microadenomas--is then difficult if the MRI technology is not optimized and if potential artifacts and traps are not recognized. Advanced MRI technology can not only depict small lesions with greater reliability, but also help in the differential diagnosis of large tumors. In these, defining the presence or absence of invasion is a particularly important task. This review describes and illustrates the radiological diagnosis of the different tumors of the sellar region, from the common prolactinomas, nonfunctioning adenomas and Rathke's cleft cysts, to the less frequent and more difficult to detect corticotroph pituitary adenomas in Cushing's disease, and other neoplastic and nonneoplastic entities. Finally, some hints are given to facilitate the differential diagnosis of sellar lesions. PMID- 27003879 TI - Correction: Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis, and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis. AB - [This corrects the article DOI: 10.1371/journal.pmed.1001611.]. PMID- 27003880 TI - SERK co-receptor kinases. PMID- 27003881 TI - Amateur photographs reveal population history of a colonial seabird. PMID- 27003882 TI - Did cortical remapping lend artist a hand? PMID- 27003883 TI - Flower Colour: How Bumblebees Handle Colours with Perceptually Changing Hues. AB - Colours are floral signals enabling bees to detect, inspect and discriminate flowers in a multitasking world. Behavioural tests now show that trained bumblebees find iridescent coloured targets more quickly and that weak iridescence does not corrupt target identification. PMID- 27003884 TI - Visual Neuroscience: How Do Moths See to Fly at Night? AB - A new study shows that moth vision trades speed and resolution for contrast sensitivity at night. These remarkable neural adaptations take place in the higher-order neurons of the hawkmoth motion vision pathway and allow the insects to see during night flights. PMID- 27003885 TI - Evolution: The End of an Ancient Asexual Scandal. AB - Bdelloid rotifers were believed to have persisted and diversified in the absence of sex. Two papers now show they exchange genes with each other, via horizontal gene transfers as known in bacteria and/or via other forms of non-canonical sex. PMID- 27003886 TI - Locomotion: Electrical Coupling of Motor and Premotor Neurons. AB - A new study has found that zebrafish motor neurons can contribute to the generation of locomotor rhythms by feedback modulation of their premotor interneurons via gap junctions. PMID- 27003887 TI - Palaeontology: Scrapes of Dinosaur Courtship. AB - Analysis of numerous trace fossils reveals 'nest scrape displays' made by dinosaurs that are analogous to those left by modern birds. PMID- 27003888 TI - Memory Processing: Ripples in the Resting Brain. AB - Recent work has shown that, during sleep, a functional circuit is created amidst a general breakdown in connectivity following fast-frequency bursts of brain activity. The findings question the unconscious nature of deep sleep, and provide an explanation for its contribution to memory processing. PMID- 27003889 TI - Translational Control: Selective Upregulation of ECM Components Drives Tumour Growth. AB - A new mechanistic link has been identified between the expression of initiator methionine tRNA and cancer progression, whereby elevated levels of this tRNA specifically drive synthesis of secretome components, resulting in a type II collagen-rich matrix that promotes tumour progression. PMID- 27003890 TI - Palaeogenomics: Mitogenomes and Migrations in Europe's Past. AB - The latest in a series of transformative studies of DNA from prehistoric Europeans focuses on mitochondrial DNA, bringing fresh surprises and filling in important details of the early stages of a European ancestry stretching back more than 40,000 years. PMID- 27003891 TI - The Eukaryotic Replisome Goes Under the Microscope. AB - The machinery at the eukaryotic replication fork has seen many new structural advances using electron microscopy and crystallography. Recent structures of eukaryotic replisome components include the Mcm2-7 complex, the CMG helicase, DNA polymerases, a Ctf4 trimer hub and the first look at a core replisome of 20 different proteins containing the helicase, primase, leading polymerase and a lagging strand polymerase. The eukaryotic core replisome shows an unanticipated architecture, with one polymerase sitting above the helicase and the other below. Additionally, structures of Mcm2 bound to an H3/H4 tetramer suggest a direct role of the replisome in handling nucleosomes, which are important to DNA organization and gene regulation. This review provides a summary of some of the many recent advances in the structure of the eukaryotic replisome. PMID- 27003892 TI - Increased risk of strontium ranelate-related SJS/TEN is associated with HLA. AB - Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN. INTRODUCTION: In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant. METHODS: Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles. RESULTS: Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n = 76). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3 months (range 3 months to 8 years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12 weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n = 5). The majority of the accrued samples were of Han Chinese descent: controls (n = 72) and cases (n = 4). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA A*33:03 (p = 0.002) and HLA-B*58:01 (p = 0.023). There was no significant association with any HLA-C or HLA-DRB1 alleles. CONCLUSIONS: This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate. PMID- 27003893 TI - Heliotherapy for Neonatal Hyperbilirubinemia in Southwest, Nigeria: A Baseline Pre-Intervention Study. AB - BACKGROUND: A novel filtered-sunlight phototherapy (FSPT) device has been demonstrated to be safe and efficacious for treating infants with neonatal jaundice in resource-constrained tropical settings. We set out to provide baseline data for evaluating the clinical impact of this device in a referral pediatric hospital. METHODS: We reviewed the medical records of infants admitted for neonatal hyperbilirubinemia in an inner-city Children's Hospital in Lagos, between January 2012 and December 2014 to determine the pattern, treatment and outcomes during the pre-intervention period. Factors associated with adverse outcomes were identified through multivariable logistic regression. RESULTS: Of the 5,229 neonatal admissions over the period, a total of 1,153 (22.1%) were admitted for neonatal hyperbilirubinemia. Complete records for 1,118 infants were available for analysis. The incidence of acute bilirubin encephalopathy (ABE) and exchange transfusion (ET) were 17.0% (95% CI: 14.9%-19.3%) and 31.5% (95% CI: 28.8%-34.3%) respectively. A total of 61 (5.5%, 95% CI: 4.3%-6.9%) of the jaundiced infants died. Weight on admission, peak total serum bilirubin (TSB), sepsis and exposure to hemolytic products were predictive of ABE, while age on admission, peak TSB, ABO incompatibility and ABE were predictive of ET. Rhesus incompatibility, asphyxia, exposure to hemolytic substances and ABE were associated with elevated mortality risk, while ET was a protective factor. Lack of routine irradiance monitoring and steady energy supply were frequent challenges for conventional blue-light phototherapy. CONCLUSIONS: Severe hyperbilirubinemia is associated with high rates of ABE and ET in this setting, and remains a significant contributor to neonatal admissions and mortality. To be impactful, FSPT, complemented with improved diagnostic facilities, should effectively curtail jaundice-related adverse outcomes in this and comparable settings. PMID- 27003894 TI - Alveolar rhabdomyosarcoma mimicking Burkitt-like lymphoma. PMID- 27003895 TI - Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle Stimulating Hormone, in Healthy Women After Single Ascending Doses. AB - OBJECTIVE: The purpose of this analysis was to develop a population pharmacokinetic model for a novel recombinant human follicle-stimulating hormone (FSH) (FE 999049) expressed from a human cell line of foetal retinal origin (PER.C6((r))) developed for controlled ovarian stimulation prior to assisted reproductive technologies. METHODS: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed effects population pharmacokinetic modelling in NONMEM 7.2.0. RESULTS: A one-compartment model with first-order absorption and elimination rates was found to best describe the data. A transit model was introduced to describe a delay in the absorption process. The apparent clearance (CL/F) and apparent volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F. CONCLUSIONS: The single-dose pharmacokinetics of FE 999049 were adequately described by a population pharmacokinetic model. The average drug concentration at steady state is expected to be reduced with increasing body weight. PMID- 27003896 TI - In vitro studies of the antiherpetic effect of photodynamic therapy. AB - The number of viral infection cases in the Department of Gynecology and Obstetrics has tended to increase over last few years. Viruses form herpesvirus and cytomegalovirus families are associated with an increased risk for recurrent pregnancy loss. Photodynamic therapy (PDT) is a promising new approach to treat viral infections in which viral particles are inactivated. It exhibits great therapeutic potential, particularly among this group of patients. This study examined the use of PDT to treat herpesvirus infection (HVI) using an in vitro model. In this study, we used the Vero sell lineage as a suitable model of HVI, strains of HSV-1 (strain VR-3) and HSV-2 (strain MS) obtained from The National Virus Collection (London, UK), the photosensitizer Fotoditazine (Veta-Grand, Russia), an AFS physiotherapeutic device (Polironic Corporation, Russia). Laser light irradiation and the photosensitizer had different cytotoxic effects on the Vero cell cultures depending on the doses used. The optimal laser light and photosensitizer doses were determined. PDT had an antiviral effect on an in vitro model of HVI in cell culture. PDT has been shown to be effective treatment for HVI in vitro, leading to a reliable decrease of viral titer. PMID- 27003897 TI - Control of hair growth using long-pulsed alexandrite laser is an efficient and cost effective therapy for patients suffering from recurrent pilonidal disease. AB - Pilonidal sinus (PNS) and its surgical management have a profound impact on hospital resources in terms of finances and productive man-hours. Surgical treatment has been the mainstay of treatment of both acute and chronic pilonidal sinus but recurrence is common. The control of hair growth in the sinus region plays an important role in preventing recurrence. Here, we discuss our experience of treating 19 patients suffering from recurrent pilonidal sinus with laser depilation and its long-term cost effectiveness. This is a retrospective study on patients who had recurrence of pilonidal sinus following multiple surgical treatments. They were treated using long-pulsed alexandrite laser for depilation in the sinus area, an outpatient procedure. Their clinical characteristics and outcomes were then evaluated. There was a significant reduction in hair density after laser treatment (p < 0.001). The disease-free period after laser treatment was significantly longer than that one after surgical treatment (p < 0.001). The average cost of repeated surgical treatment per disease-free month was significantly higher than that of laser treatment (p < 0.001). Evidence suggests the role of natal cleft hair growth in the evolution of the pilonidal disease; therefore, control of hair growth should be considered as an adjunct to the initial treatment via surgery. Compared to surgical treatment of recurrences, laser depilation is an efficient and cost-effective method of preventing recurrence and reducing morbidity and loss of man-hours. We suggest that laser depilation of the pilonidal sinus should be funded by clinical commissioning groups. PMID- 27003898 TI - Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure. AB - BACKGROUND: Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO2 ) target range (85-92%) from April 2011. Lower SpO2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO2 target range, during the early postnatal stage, increases the risk of DA closure failure. METHODS: Infants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84-100% in study period 1 and 85-92% in period 2. RESULTS: Eighty-two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. CONCLUSION: Lower early postnatal oxygen saturation target range increases the risk of DA closure failure. PMID- 27003899 TI - Role of cytokine gene polymorphisms in acute and chronic kidney disease following liver transplantation. AB - PURPOSE: Development of renal dysfunction, including acute kidney injury (AKI) and chronic kidney disease (CKD), after liver transplantation (LT) remains a critical issue adversely affecting patient survival in both the short and long term. Previous reports have suggested that inflammatory and antiinflammatory cytokines and their functionally relevant gene polymorphisms may play critical roles in the development of AKI and CKD. However, the involvement of these cytokines and their gene polymorphisms in renal deterioration following LT remains unclear. METHODS: We examined 62 recipients who underwent LT at Nagoya University between 2004 and 2009 and who had survived for at least 1 year. The following gene polymorphisms in recipients were analyzed: tumor necrosis factor-A (TNFA) T-1031C, interleukin-2 (IL2) T-330G, IL10 C-819T, IL13 C-1111T, transforming growth factor-B (TGFB) T29C, and IL4 T-33C. RESULTS: Thirteen patients (21 %) developed AKI within 4 weeks after LT. Of the investigated gene polymorphisms, the IL4 -33 T/T genotype was significantly associated with higher incidence of AKI compared with the other two genotypes [hazard ratio (HR) = 5.48, 95 % confidence interval (CI) 1.18-25.52, p = 0.03]. On the other hand, 16 patients (26 %) had developed CKD at median follow-up of 9.2 years after LT. We showed the lack of association between investigated gene polymorphisms in recipients and CKD development. CONCLUSIONS: The IL4 -33 T/T genotype might be a risk factor for AKI in LT, and this might contribute to earlier withdrawal of immunosuppressive agents to minimize renal toxicity. In contrast, none of the investigated cytokine gene polymorphisms were associated with CKD. PMID- 27003900 TI - Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders. AB - We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2 hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI. PMID- 27003901 TI - Quality of life and survival survey of cancer cachexia in advanced non-small cell lung cancer patients-Japan nutrition and QOL survey in patients with advanced non small cell lung cancer study. AB - PURPOSE: Although cancer cachexia is mainly characterized by persistent loss of body weight (BW), usually in response to a malignancy, the pathophysiology of cachexia remains unresolved. To elucidate the relationship between the loss of BW and other related clinical factors, we conducted a nationwide, multi institutional, prospective, observational study in patients with advanced non small cell lung cancer (NSCLC). METHODS: Treatment-naive stage IV NSCLC patients with an Eastern Cooperative Oncology Group performance status (PS) of 0-2 were eligible. BW, handgrip strength (HGS), quality of life (QOL), Karnofsky Performance Scale (KPS), biochemical parameters, and survival were evaluated at baseline and every 4 weeks for 1 year. The relationship between BW loss and other factors was examined by linear regression analysis. Estimated survival curves were drawn by the Kaplan-Meier method and applied by the log-rank test. Clinical factors associated with cancer cachexia were identified through principal component analysis. The generalized estimating equation approach was used to analyze the deterioration of QOL resulting from the progression of cachexia. RESULTS: A total of 406 patients were analyzed. BW loss was significantly associated with worsening of QOL, HGS, KPS, and biochemical parameters. The incidence of BW loss was observed throughout the study period. Overall survival was significantly shorter in patients as BW loss progressed. BW loss, decrease in HGS, anorexia, and fatigue were identified as core factors of cachexia that contributed to the deterioration of QOL. CONCLUSION: BW loss most likely deteriorated QOL and shortened survival in patients with advanced NSCLC and should be closely monitored. PMID- 27003902 TI - Patients' understanding of treatment goals and disease course and their relationship with optimism, hope, and quality of life: a preliminary study among advanced breast cancer outpatients before receiving palliative treatment. AB - PURPOSE: The aims of this study were to explore advanced breast cancer patients' knowledge of treatment intent and expectation of illness course and to evaluate their relationship with optimism, hope, and quality of life (QoL). METHODS: Patients with advanced breast cancer (n = 55) who were treated in the ambulatory clinic of the University of Hacettepe were included in the study. They completed Life Orientation Scale, The Hope Scale, and the European Organization for Research and Treatment of Cancer Quality of Life questionnaires. The data regarding the knowledge of illness progression and the perceptions of therapy intent were assessed using self-administered open-ended questionnaires that were answered by the patients. RESULTS: The data revealed that 58.2 % of the patients had an inaccurate perception of treatment intent, believing the aim of treatment was cure, whereas only 38.2 % of the patients had a realistic expectation that their disease may remain stable or may progress over a year. In addition, the awareness of disease progression and perception of goals of treatment was significantly related to hope and optimism scores but not to QoL. CONCLUSIONS: A large proportion of patients diagnosed with advanced breast cancer believed that their treatment was "curative", and they would improve within a year. Findings of our study suggest that patients with inaccurate perception of treatment intent and unrealistic expectation of prognosis have higher hope and optimism scores than those who do not, but there were no significant differences in terms of global health status. PMID- 27003903 TI - Functional vitamin B12 deficiency in advanced malignancy: implications for the management of neuropathy and neuropathic pain. AB - BACKGROUND AND AIM: Treatment of neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignancy is often unsuccessful. Functional vitamin B12 deficiency, defined by elevated levels of the B12 dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal B12 values, may cause neuropathy and is associated with disorders linked to increased oxidative stress. Since both cancer and neurotoxic antineoplastic agents increase oxidative stress, a role for functional B12 deficiency in CIPN was considered. METHODS: A retrospective record review of 241 cancer subjects evaluated by the adult palliative care service for B12 deficiency in a university based cancer center between October 2008 and September 2012 with measurement of B12, MMA, and/or homocysteine levels was performed. RESULTS: B12 values were elevated (>900 pg/ml) in 30 % and low (<=300 pg/ml) in 17 % of subjects tested. Elevated MMA (>250 nmol/l) and homocysteine (>12.1 MUmol/l) levels occurred in 38 and 23 % of subjects respectively and at least one metabolite was increased in 54 % of evaluable subjects. Even when B12 values were >=1500 pg/ml (n = 36), increased MMA and homocysteine values occurred in 31 and 23 % of subjects, respectively. B12 therapy decreased MMA values in all four subjects studied and improved neurologic findings in the three subjects tested. CONCLUSIONS: Functional vitamin B12 deficiency is common in subjects with advanced malignancy. Further studies are needed to determine if this disorder is a risk factor for CIPN and if B12 therapy has a role in the management and/or prevention of neuropathy and neuropathic pain in this population. PMID- 27003905 TI - Transferring an optimized TAP-toolbox for the isolation of protein complexes to a portfolio of rice tissues. AB - Proteins are the cell's functional entities. Rather than operating independently, they interact with other proteins. Capturing in vivo protein complexes is therefore crucial to gain understanding of the function of a protein in a cellular context. Affinity purification coupled to mass spectrometry has proven to yield a wealth of information about protein complex constitutions for a broad range of organisms. For Oryza sativa, the technique has been initiated in callus and shoots, but has not been optimized ever since. We translated an optimized tandem affinity purification (TAP) approach from Arabidopsis thaliana toward Oryza sativa, and demonstrate its applicability in a variety of rice tissues. A list of non-specific and false positive interactors is presented, based on re occurrence over more than 170 independent experiments, to filter bona fide interactors. We demonstrate the sensitivity of our approach by isolating the complexes for the rice ANAPHASE PROMOTING COMPLEX SUBUNIT 10 (APC10) and CYCLIN DEPENDENT KINASE D (CDKD) proteins from the proliferation zone of the emerging fourth leaf. Next to APC10 and CDKD, we tested several additional baits in the different rice tissues and reproducibly retrieved at least one interactor for 81.4 % of the baits screened for in callus tissue and T1 seedlings. By transferring an optimized TAP tag combined with state-of-the-art mass spectrometry, our TAP protocol enables the discovery of interactors for low abundance proteins in rice and opens the possibility to capture complex dynamics by comparing tissues at different stages of a developing rice organ. PMID- 27003906 TI - Plant-microbe symbiotic interactions. PMID- 27003907 TI - Hormones and nitrate: a two-way connection. AB - During their sessile mode of life, plants need to endure variations in their environment such as a drastic variability in the nutrient concentration in soil solution. It is almost trivial to say that such fluctuations in the soil modify plant growth, development and phase transitions. However, the signaling pathways underlying the connections between nitrogen related signaling and hormonal signaling controlling growth are still poorly documented. This review is meant to present how nitrate/nitrogen controls hormonal pathways. Furthermore, it is very interesting to highlight the increasing evidence that the hormonal signaling pathways themselves seem to feed back control of the nitrate/nitrogen transport and assimilation to adapt nutrition to growth. This thus defines a feed-forward cycle that finely coordinates plant growth and nutrition. PMID- 27003908 TI - Dynamic Polymeric Microtubes for the Remote-Controlled Capture, Guidance, and Release of Sperm Cells. AB - Remote-controlled release of single sperm cells is demonstrated by the use of polymeric microtubes that unfold upon temperature increase to 38 degrees C. Thermoresponsive, ferromagnetic multilayers are tailored to catch sperm cells and remotely control them by external magnetic fields. These polymeric spermbots are propelled by the sperm flagella. When the temperature is increased, the tubes unfold and the cell is set free. PMID- 27003909 TI - Antibacterial activity of a new broad-spectrum antibiotic covalently bound to titanium surfaces. AB - Biofilm-associated infections, particularly those caused by Staphylococcus aureus, are a major cause of implant failure. Covalent coupling of broad-spectrum antimicrobials to implants is a promising approach to reduce the risk of infections. In this study, we developed titanium substrates on which the recently discovered antibacterial agent SPI031, a N-alkylated 3, 6-dihalogenocarbazol 1 (sec-butylamino)-3-(3,6-dichloro-9H-carbazol-9-yl)propan-2-ol, was covalently linked (SPI031-Ti). We found that SPI031-Ti substrates prevent biofilm formation of S. aureus and Pseudomonas aeruginosa in vitro, as quantified by plate counting and fluorescence microscopy. To test the effectiveness of SPI031-Ti substrates in vivo, we used an adapted in vivo biomaterial-associated infection model in mice in which SPI031-Ti substrates were implanted subcutaneously and subsequently inoculated with S. aureus. Using this model, we found a significant reduction in biofilm formation (up to 98%) on SPI031-Ti substrates compared to control substrates. Finally, we demonstrated that the functionalization of the titanium surfaces with SPI031 did not influence the adhesion and proliferation of human cells important for osseointegration and bone repair. In conclusion, these data demonstrate the clinical potential of SPI031 to be used as an antibacterial coating for implants, thereby reducing the incidence of implant-associated infections. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2191-2198, 2016. PMID- 27003910 TI - Lateral pressure-mediated protein partitioning into liquid-ordered/liquid disordered domains. AB - We have studied the contributions of stored elastic energies in liquid-ordered (Lo) and liquid-disordered (Ld) domains to transmembrane proteins using the lateral pressure concept. In particular we applied previously reported experimental data for the membrane thickness, intrinsic curvature and bending elasticities of coexisting Lo/Ld domains to calculate whether proteins of simple geometric shapes would preferentially diffuse into Lo or Ld domains and form oligomers of a certain size. For the studied lipid mixture we generally found that proteins with convex shapes prefer sorting to Ld phases and the formation of large clusters. Lo domains in turn would be enriched in monomers of concave shaped proteins. We further observed that proteins which are symmetric with respect to the bilayer center prefer symmetric Lo or Ld domains, while asymmetric proteins favor a location in domains with Lo/Ld asymmetry. In the latter case we additionally retrieved a strong dependence on protein directionality, thus providing a mechanism for transmembrane protein orientation. PMID- 27003911 TI - The Spatial Relationship and Surface Projection of Canine Sciatic Nerve and Sacrotuberous Ligament: A Perineal Hernia Repair Perspective. AB - Sciatic nerve entrapment can occur as post-operative complication of perineal hernia repair when sacrotuberous ligament is incorporated during hernia deficit closure. This results in sciatic sensory loss and paralysis of the hind leg. This study investigated the spatial relationship of sciatic nerve and sacrotuberous ligament and their surface topographic projection of 68 cadavers (29 Beagles and 39 Taiwanese mongrels) with various heights (25-56 cm). By gross dissection, the sacrotuberous ligament and sciatic nerve were exposed and their distance in between was measured along four parts (A, B, C, D) of sacrotuberous ligament. The present study revealed that the C was the section of sacrotuberous ligament where the sciatic nerve and the sacrotuberous ligament are closest to each other. Furthermore, a positive correlation was observed between C and height of the dogs. From the present study, we found that the C in smaller dogs has the shortest distance between the sciatic nerve and the sacrotuberous ligament, and thus the most vulnerable to sciatic nerve entrapment, and needs to be avoided or approached cautiously during perineal hernia repair. PMID- 27003912 TI - Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study. AB - AIM: To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. METHODS AND RESULTS: 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble(r)). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. CONCLUSIONS: RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress. PMID- 27003913 TI - Functional Diversification after Gene Duplication: Paralog Specific Regions of Structural Disorder and Phosphorylation in p53, p63, and p73. AB - Conformational and functional flexibility promote protein evolvability. High evolvability allows related proteins to functionally diverge and perhaps to neostructuralize. p53 is a multifunctional protein frequently referred to as the Guardian of the Genome-a hub for e.g. incoming and outgoing signals in apoptosis and DNA repair. p53 has been found to be structurally disordered, an extreme form of conformational flexibility. Here, p53, and its paralogs p63 and p73, were studied for further insights into the evolutionary dynamics of structural disorder, secondary structure, and phosphorylation. This study is focused on the post gene duplication phase for the p53 family in vertebrates, but also visits the origin of the protein family and the early domain loss and gain events. Functional divergence, measured by rapid evolutionary dynamics of protein domains, structural properties, and phosphorylation propensity, is inferred across vertebrate p53 proteins, in p63 and p73 from fish, and between the three paralogs. In particular, structurally disordered regions are redistributed among paralogs, but within clades redistribution of structural disorder also appears to be an ongoing process. Despite its deemed importance as the Guardian of the Genome, p53 is indeed a protein with high evolvability as seen not only in rearranged structural disorder, but also in fluctuating domain sequence signatures among lineages. PMID- 27003914 TI - Current Status: Site-Specific Antibody Drug Conjugates. AB - Antibody drug conjugates (ADCs), a promising class of cancer biopharmaceuticals, combine the specificity of therapeutic antibodies with the pharmacological potency of chemical, cytotoxic drugs. Ever since the first ADCs on the market, a plethora of novel ADC technologies has emerged, covering as diverse aspects as antibody engineering, chemical linker optimization and novel conjugation strategies, together aiming at constantly widening the therapeutic window for ADCs. This review primarily focuses on novel chemical and biotechnological strategies for the site-directed attachment of drugs that are currently validated for 2nd generation ADCs to promote conjugate homogeneity and overall stability. PMID- 27003915 TI - A Geodesics-Based Surface Parameterization to Assess Aneurysm Progression. AB - Abdominal aortic aneurysm (AAA) intervention and surveillance is currently based on maximum transverse diameter, even though it is recognized that this might not be the best strategy. About 10% of patients with small AAA transverse diameters, for whom intervention is not considered, still rupture; while patients with large AAA transverse diameters, for whom intervention would have been recommended, have stable aneurysms that do not rupture. While maximum transverse diameter is easy to measure and track in clinical practice, one of its main drawbacks is that it does not represent the whole AAA and rupture seldom occurs in the region of maximum transverse diameter. By following maximum transverse diameter alone clinicians are missing information on the shape change dynamics of the AAA, and clues that could lead to better patient care. We propose here a method to register AAA surfaces that were obtained from the same patient at different time points. Our registration method could be used to track the local changes of the patient-specific AAA. To achieve registration, our procedure uses a consistent parameterization of the AAA surfaces followed by strain relaxation. The main assumption of our procedure is that growth of the AAA occurs in such a way that surface strains are smoothly distributed, while regions of small and large surface growth can be differentiated. The proposed methodology has the potential to unravel different patterns of AAA growth that could be used to stratify patient risks. PMID- 27003916 TI - China's Contribution to Anesthesiology Research: A 10-Year Survey of the Literature. AB - BACKGROUND: Anesthesiology has advanced in China over the past decade. We compared the trends in publication of anesthesiology articles from China between 2005 and 2014 with the trends in 5 developed countries. METHODS: We included all journals listed in the ''Anesthesiology'' category of Journal Citation Reports. Anesthesiology-related publications from 2005 to 2014 were retrieved from the PubMed and Web of Knowledge online databases. The total number of articles, publication type categories, number of citations, and citation rate (number of citations/years since publication) were analyzed. The sample size was the n = 10 years for all confidence intervals and P values. We additionally evaluated the total number of articles published in the 10 top-ranking journals. RESULTS: From 2005 to 2014, 41,344 articles were published in anesthesiology journals. Of these, 3.07% were contributed by authors from Chinese institutions. Although this contribution was less than the Unites States, Great Britain, Germany, France, or Japan, publications from Chinese institutions grew at an annual rate of 13% (95% confidence interval: 3.08%-23.38%, P < 0.001, r = 0.903). Chinese institutions produced relatively more basic research reports than clinical investigations. China ranked before Great Britain (221 articles) and France (245 articles) in basic research, with 448 basic researches publications during the study period. The articles from China averaged 2.24 citations per year, comparable to the articles from the United States (2.71, P = 0.545), Great Britain (2.57, P = 0.999), Germany (2.35, P = 0.999), France (1.50, P = 0.520), and Japan (1.24, P = 0.065). In the 10 highest impact anesthesiology journals, China published 780 articles during the decade. The 3 journals with the most publications from Chinese institutions were Anesthesia & Analgesia, Anesthesiology, and Acta Anaesthesiologica Scandinavica. CONCLUSIONS: In the studied decade, anesthesiology research published by Chinese institutions lagged behind publications from developed countries. There was a steady increase in the number of articles every year, resulting in recent rates of publication similar to several developed countries. The citation rate of articles from Chinese institutions was similar to the citation rate of articles from developed countries, indicating that the quality of articles from China in these journals is comparable to the quality from developed countries. PMID- 27003917 TI - The Effect of Dexmedetomidine on Postoperative Opioid Consumption and Pain After Major Spine Surgery. AB - BACKGROUND: Adult deformity correction spine surgery can be associated with significant perioperative pain because of inflammatory, muscular, neuropathic, and postsurgical pain. alpha-2 Agonists have intrinsic antinociceptive and antihyperalgesic properties that can potentially reduce both postoperative opioid consumption and pain. We hypothesized that intraoperative dexmedetomidine would reduce postoperative opioid consumption and improve pain scores in deformity correction spine surgery. METHODS: Patients undergoing >3 levels of thoracic and/or lumbar spine surgery were enrolled in this prospective randomized double blind study to receive either dexmedetomidine (1 MUg/kg load followed by a continuous infusion of 0.5 MUg/kg/h) or saline. Both groups received a single dose of 0.2 mg/kg (ideal body weight) of methadone at the start of surgery. Intraoperative fentanyl was administered based on the clinical and hemodynamic signs suggestive of increased nociception. Postoperative analgesia was provided with a hydromorphone patient-controlled analgesia pump. Opioid consumption and pain scores were recorded at 24, 48, and 72 hours after surgery. RESULTS: One hundred forty-two participants were enrolled with 131 completing the study. There was no significant difference in demographics (age, sex, weight, and ASA physical status), percentage of participants with preoperative opioid use, and daily median opioid consumption between the groups. The study was terminated early after interim analysis. Intraoperative opioid use was reduced in the dexmedetomidine arm (placebo versus dexmedetomidine, median [25%-75% interquartile range]: 7 [3-15] vs 3.5 [0-11] mg morphine equivalents, P = 0.04) but not at 24 hours: 49 (30-78) vs 61 (34-77) mg morphine equivalents, P = 0.65, or 48 hours: 41 (28-68) vs 40 (23-64) mg morphine equivalents, P = 0.60, or 72 hours: 29 (15-59) vs 30 (14-46) mg morphine equivalents, P = 0.58. The Wilcoxon Mann-Whitney odds are 1.11 with 97.06% confidence interval (0.71-1.76) for opioid consumption. No difference in pain score, as measured by the 11-point visual analog scale, was seen at 24 hours (placebo versus dexmedetomidine, median [25% 75% interquartile range]: 7 [5-7] vs 6 [4-7], P = 0.12) and 48 hours (5 [3-7] vs 5 [3-6], P = 0.65). There was an increased incidence of bradycardia (placebo: 37% vs dexmedetomidine: 59% P = 0.02) and phenylephrine use in the dexmedetomidine group (placebo: 59% versus dexmedetomidine: 78%, P = 0.03). CONCLUSIONS: Intraoperative dexmedetomidine does not reduce postoperative opioid consumption or improve pain scores after multilevel deformity correction spine surgery. PMID- 27003918 TI - Sevoflurane Inhibits Glutamate-Aspartate Transporter and Glial Fibrillary Acidic Protein Expression in Hippocampal Astrocytes of Neonatal Rats Through the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) Pathway. AB - BACKGROUND: The mechanisms underlying general anesthesia-induced neurotoxicity are unclear. Astrocytes have been recognized as important contributors to neuronal development. Until now, the response of the astrocytes to neonatal general anesthetic exposure has been unreported. METHODS: Postnatal day 7 rats received 2.5% sevoflurane for 6 hours. Expressions of glial fibrillary acidic protein (GFAP) and glutamate-aspartate transporter (GLAST) and phosphorylation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway were detected on days 1, 3, 7, and 14 after sevoflurane inhalation. In addition, cultured astrocytes were exposed to 2.5% sevoflurane for 2 hours and GFAP, GLAST expressions, and JAK/STAT phosphorylation were evaluated. Furthermore, we pharmacologically disrupted JAK/STAT signaling in vivo by treatment with the JAK/STAT inhibitor AG490 and in vitro by treatment with JAK inhibitor I to detect the consequent expression of GFAP and GLAST. RESULTS: Sevoflurane induced a robust decrease of GFAP and GLAST expression in hippocampal tissue compared with sham control groups at 1 to 14 days after sevoflurane exposure. Immunohistochemistry showed colocalization of GFAP, GLAST, and pSTAT3 in the hippocampal CA1 region. Western blot analysis also revealed a significant decrease of pJAK1, pJAK2, and pSTAT3 in the sevoflurane group. In vitro study showed that GFAP, GLAST, pJAK1, pJAK2, and pSTAT3 expressions in cultured astrocytes were remarkably decreased at 24 to 48 hours after sevoflurane treatment. Either AG490 or JAK inhibitor I significantly decreased expressions of GFAP and GLAST in hippocampus or cultured astrocytes. CONCLUSIONS: Astrocytic GLAST was inhibited by sevoflurane in the hippocampus of neonatal rats. Inactivation of the JAK/STAT pathway possibly contributes to this effect of sevoflurane. Astrocytic dysfunction induced by sevoflurane may contribute to its neurotoxicity in the developing brain. PMID- 27003919 TI - Identification of Regulatory Mutations in SERPINC1 Affecting Vitamin D Response Elements Associated with Antithrombin Deficiency. AB - Antithrombin is a crucial anticoagulant serpin whose even moderate deficiency significantly increases the risk of thrombosis. Most cases with antithrombin deficiency carried genetic defects affecting exons or flanking regions of SERPINC1.We aimed to identify regulatory mutations inSERPINC1 through sequencing the promoter, intron 1 and 2 of this gene in 23 patients with antithrombin deficiency but without known genetic defects. Three cases with moderate antithrombin deficiency (63-78%) carried potential regulatory mutations. One located 200 bp before the initiation ATG and two in intron 1. These mutations disrupted two out of five potential vitamin D receptor elements (VDRE) identified in SERPINC1 with different software. One genetic defect, c.42-1060_-1057dupTTGA, was a new low prevalent polymorphism (MAF: 0.01) with functional consequences on plasma antithrombin levels. The relevance of the vitamin D pathway on the regulation of SERPINC1 was confirmed in a cell model. Incubation of HepG2 with paricalcitol, a vitamin D analog, increased dose-dependently the levels of SERPINC1transcripts and antithrombin released to the conditioned medium. This study shows further evidence of the transcriptional regulation of SERPINC1 by vitamin D and first describes the functional and pathological relevance of mutations affecting VDRE of this gene. Our study opens new perspectives in the search of new genetic defects involved in antithrombin deficiency and the risk of thrombosis as well as in the design of new antithrombotic treatments. PMID- 27003920 TI - Targeting Complement Pathways During Cold Ischemia and Reperfusion Prevents Delayed Graft Function. AB - The complement system plays a critical role in ischemia-reperfusion injury (IRI) mediated delayed graft function (DGF). To better understand the roles of complement activation pathways in IRI in kidney transplantation, donor kidneys were treated ex vivo with terminal complement pathway (TP) inhibitor, anti-rat C5 mAb 18A10, or complement alternative pathway (AP) inhibitor TT30 for 28 h at 4 degrees C pretransplantation in a syngeneic kidney transplantation rat model. All 18A10- and 67% of TT30-pretreated grafts, but only 16.7% of isotype control pretreated grafts, survived beyond day 21 (p < 0.01). Inhibitor treatment in the final 45 min of 28-h cold ischemia (CI) similarly improved graft survival. Systemic posttransplant treatment with 18A10 resulted in 60% increased graft survival beyond day 21 (p < 0.01), while no TT30-treated rat survived > 6 days. Our results demonstrate that AP plays a prominent role during CI and that blocking either the AP or, more effectively the TP prevents ischemic injury and subsequent DGF. Multiple complement pathways may be activated and contribute to reperfusion injury; blocking the TP, but not the AP, posttransplant is effective in preventing reperfusion injury and increasing graft survival. These results demonstrate the feasibility of using complement inhibitors for prevention of DGF in humans. PMID- 27003921 TI - Consumer Acceptance of Bars and Gummies with Unencapsulated and Encapsulated Resveratrol. AB - The addition of resveratrol, a polyphenol found in red wine and peanuts, to food products would help to provide the health benefits associated with the compound to the consumer in a wide array of food matrices. The bitterness of resveratrol and instability of its bioactive form in light are 2 major challenges with the incorporation of the compound into food products. Microencapsulation in a sodium caseinate matrix was utilized as a strategy to overcome these challenges. The objective of this research was to show the application of the resveratrol microcapsules in easy-to-consume foods. Consumer acceptance was evaluated for gummies and bars with encapsulated resveratrol in comparison to the controls. Four different controls were used: 1) without any resveratrol OR protein (Plain), 2) unencapsulated resveratrol (Resv), 3) sodium caseinate and unencapsulated resveratrol just mixed without encapsulation (P + R), and 4) sodium caseinate only (PRO). Two concentrations of resveratrol that have been shown to offer therapeutic effects in humans were tested (10 and 40 mg/d). The overall liking, evaluated using a 9-point scale, of bars with 10 mg of encapsulated resveratrol did not differ significantly from the control without any added resveratrol and protein (Plain) or from the controls with equivalent protein and/or resveratrol concentrations. For gummies, the samples with the resveratrol microcapsules had a significantly lower overall liking than the controls with the same protein and/or resveratrol content. This research demonstrated application of resveratrol microcapsules into easy-to-consume food products in order to deliver the health benefits to the consumer. PMID- 27003923 TI - The role of autonomic dysfunction in cirrhotic patients before and after liver transplantation. Review of the literature. AB - In patients affected by hepatic cirrhosis, autonomic dysfunction is a common finding; usually it is asymptomatic but it may correlate with increased mortality and morbidity before, during and after liver transplant, due to hemodynamic instability in the course of stressful events like sepsis, gastrointestinal bleeding and reperfusion after transplantation surgery. Hyperdynamic circulation and hepatic dysfunction seem to play a role in the pathogenesis of autonomic dysfunction, even if pathophysiological mechanisms are not completely known. We present a revision of previous literature about prevalence, pathophysiological mechanisms, clinical features, and mortality and morbidity of autonomic dysfunction secondary to hepatic cirrhosis. PMID- 27003924 TI - The effect of infrapatellar fat pad resection on outcomes post-total knee arthroplasty: a systematic review. AB - INTRODUCTION: The infrapatellar fat pad (IPFP) is resected in approximately 88 % of total knee arthroplasty (TKA) surgeries. The aim of this review is to investigate the impact of the IPFP resection on clinical outcomes post-TKA. MATERIALS AND METHODS: A systematic search of five major databases for all relevant articles published until May, 2015 was conducted. Studies comparing the effect of IPFP resection and preservation on outcomes post-TKA were included. Each study was then assessed individually for level of evidence and risk of bias. Studies were then grouped into post-operative outcomes and given a level of evidence ranking based on the collective strength of evidence. RESULTS: The systematic review identified ten studies suitable for inclusion, with a total of 10,163 patients. Within these ten studies, six post-operative outcomes were identified; knee pain, vascularisation of the patella, range of motion (ROM), patella tendon length/patella infera, wound complications and patient satisfaction. Moderate evidence increased knee pain with IPFP resection post-TKA was found. Conflicting evidence was found for patella vascularisation and patellar tendon length post-TKA. Moderate evidence for no difference in ROM was found. One low quality study was found for wound complications and patient satisfaction. CONCLUSIONS: This systematic review is limited by the lack of level one randomised controlled trials (RCTs). There is however moderate level evidence that IPFP resection increases post-operative knee pain. Further level one RCTs are required to produce evidence-based guidelines regarding IPFP resection. Systematic Review Level of Evidence: 3. PMID- 27003925 TI - A mixed-method systematic review and meta-analysis of mental health professionals' attitudes toward smoking and smoking cessation among people with mental illnesses. AB - BACKGROUND AND AIMS: People with mental illnesses and substance abuse disorders are important targets for smoking cessation interventions. Mental health professionals (MHPs) are ideally placed to deliver interventions, but their attitudes may prevent this. This systematic review therefore aimed to identify and estimate quantitatively MHPs attitudes towards smoking and main barriers for providing smoking cessation support and to explore these attitudes in-depth through qualitative synthesis. METHODS: The online databases AMED, EMBASE, Medline, PsychINFO, HMIC and CINAHL were searched in March 2015 using terms relating to three concepts: 'attitudes', 'mental health professionals' and 'smoking cessation'. Quantitative or qualitative studies of any type were included. Proportions of MHPs' attitudes towards smoking and smoking cessation were pooled across studies using random effects meta-analysis. Qualitative findings were evaluated using thematic synthesis. RESULTS: Thirty-eight studies including 16 369 participants were eligible for inclusion. Pooled proportions revealed that 42.2% [95% confidence interval (CI) = 35.7-48.8] of MHPs reported perceived barriers to smoking cessation interventions, 40.5% (95% CI = 30.4-51.0) negative attitudes towards smoking cessation and 45.0% (95% CI = 31.9-58.4) permissive attitudes towards smoking. The most commonly held beliefs were that patients are not interested in quitting (51.4%, 95% CI = 33.4-69.2) and that quitting smoking is too much for patients to take on (38%, 95% CI = 16.4-62.6). Qualitative findings were consistent with quantitative results, revealing a culture of smoking as 'the norm' and a perception of cigarettes as a useful tool for patients and staff. CONCLUSIONS: A significant proportion of mental health professionals hold attitudes and misconceptions that may undermine the delivery of smoking cessation interventions; many report a lack of time, training and confidence as main barriers to addressing smoking in their patients. PMID- 27003926 TI - The Impact of Surgical Experience on Major Intraoperative Aneurysm Rupture and Their Consequences on Outcome: A Multivariate Analysis of 538 Microsurgical Clipping Cases. AB - The incidence and associated mortality of major intraoperative rupture (MIOR) in intracranial aneurysm surgery is diverse. One possible reason is that many studies failed to consider and properly adjust the factor of surgical experience in the context. We conducted this study to clarify the role of surgical experience on MIOR and associated outcome. 538 consecutive intracranial aneurysm surgeries performed on 501 patients were enrolled in this study. Various potential predictors of MIOR were evaluated with stratified analysis and multivariate logistic regression. The impact of surgical experience and MIOR on outcome was further studied in a logistic regression model with adjustment of each other. The outcome was evaluated using the Glasgow Outcome Scale one year after the surgery. Surgical experience and preoperative Glasgow Coma Scale (GCS) were identified as independent predictors of MIOR. Experienced neurovascular surgeons encountered fewer cases of MIOR compared to novice neurosurgeons (MIOR, 18/225, 8.0% vs. 50/313, 16.0%, P = 0.009). Inexperience and MIOR were both associated with a worse outcome. Compared to experienced neurovascular surgeons, inexperienced neurosurgeons had a 1.90-fold risk of poor outcome. On the other hand, MIOR resulted in a 3.21-fold risk of unfavorable outcome compared to those without it. Those MIOR cases managed by experienced neurovascular surgeons had a better prognosis compared with those managed by inexperienced neurosurgeons (poor outcome, 4/18, 22% vs. 30/50, 60%, P = 0.013). PMID- 27003927 TI - DNA methylation dynamics in plants and mammals: overview of regulation and dysregulation. AB - DNA methylation is a major epigenetic marking mechanism regulating various biological functions in mammals and plant. The crucial role of DNA methylation has been observed in cellular differentiation, embryogenesis, genomic imprinting and X-chromosome inactivation. Furthermore, DNA methylation takes part in disease susceptibility, responses to environmental stimuli and the biodiversity of natural populations. In plant, different types of environmental stress have demonstrated the ability to alter the archetype of DNA methylation through the genome, change gene expression and confer a mechanism of adaptation. DNA methylation dynamics are regulated by three processes de novo DNA methylation, methylation maintenance and DNA demethylation. These processes have their similarities and differences between mammals and plants. Furthermore, the dysregulation of DNA methylation dynamics represents one of the primary molecular mechanisms of developing diseases in mammals. This review discusses the regulation and dysregulation of DNA methylation in plants and mammals. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27003928 TI - Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis. AB - A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of ?163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs. PMID- 27003929 TI - High Glucose Enhances oxLDL-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells Largely via Inducing Lectin-Like ox-LDL Receptor-1. AB - BACKGROUND: High blood glucose is characteristic of diabetic nephropathy (DN). Both lectin-like ox-LDL receptor-1 (LOX-1) and renal tubular epithelial cells apoptosis reportedly are important for the pathogenesis and progression of DN. In this study, we explored the regulatory effects of high glucose on the expression of LOX-1 and its impact on oxLDL-induced apoptosis in human renal proximal tubular epithelial cells (HRPTEpCs). METHODS: Primary HRPTEpCs were treated with high glucose with or without concurrent treatment with selective p38 mitogen activated protein kinase (MAPK) inhibitor PD169316 or lentiviral knockdown of LOX 1. HRPTEpCs cultured in normal glucose concentration (5.5 mmol/l) was used as a control. RESULTS AND CONCLUSION: High glucose concentration dependency increased the expression of LOX-1, which led to increased ox-LDL binding in HRPTEpCs. In addition, high glucose upregulated the LOX-1 gene promoter activity but not its mRNA stability in HRPTEpCs; the effect was abolished by PD169316. Furthermore, high glucose markedly enhanced oxLDL-induced apoptosis in HRPTEpCs, which was largely abolished by knockdown of LOX-1. This study demonstrates that high glucose induces the expression of LOX-1 at the gene promoter/transcription level mainly by a p38 MAPK-dependent mechanism, which enhances oxLDL-induced apoptosis in renal tubular epithelial cells. It adds new insights into the molecular mechanisms underlying DN. PMID- 27003930 TI - Memorizing Shape to Orient Cell Division. AB - A century ago, Oscar Hertwig discovered that cells orient their cleavage plane orthogonal to their long axis. Reporting recently in Nature, Bosveld et al. (2016) shed light on how, showing that NuMA/Mud localization at tricellular junctions provides mitotic cells with the memory of interphase shape used to orient cleavage plane. PMID- 27003931 TI - KRABs RegulaTE Gene Expression beyond the Embryo. AB - Transposable element (TE) silencing is initiated early in mammalian development and maintained during somatic differentiation. Reporting in this issue of Developmental Cell, Ecco et al. (2016) show that in somatic tissues, TE regulation, and its subsequent effect on host gene transcription, is dynamic rather than locked in a silent state. PMID- 27003932 TI - Embracing the Enemy: Cell-to-Cell Force Transmission Enhances Cytotoxicity. AB - Cells respond to the mechanical properties of their environment, but how biomechanics contributes to intercellular signaling remains unclear. Reporting in Cell, Basu et al. (2016) showed that forces exerted by cytotoxic T lymphocytes enhance the function of the pore-forming protein perforin, thereby leading to more effective target cell killing. PMID- 27003933 TI - Approaching Perfection: New Developments in Zebrafish Genome Engineering. AB - Programmable nucleases have revolutionized zebrafish genetics by enabling targeted genome modifications. In this issue of Developmental Cell, Hoshijima et al. (2016) take genome modification in the zebrafish to the next level, demonstrating the efficient use of homologous recombination to make genetic tools for a range of applications. PMID- 27003934 TI - Emerging Imaging and Genomic Tools for Developmental Systems Biology. AB - Animal development is a complex and dynamic process orchestrated by exquisitely timed cell lineage commitment, divisions, migration, and morphological changes at the single-cell level. In the past decade, extensive genetic, stem cell, and genomic studies provided crucial insights into molecular underpinnings and the functional importance of genetic pathways governing various cellular differentiation processes. However, it is still largely unknown how the precise coordination of these pathways is achieved at the whole-organism level and how the highly regulated spatiotemporal choreography of development is established in turn. Here, we discuss the latest technological advances in imaging and single cell genomics that hold great promise for advancing our understanding of this intricate process. We propose an integrated approach that combines such methods to quantitatively decipher in vivo cellular dynamic behaviors and their underlying molecular mechanisms at the systems level with single-cell, single molecule resolution. PMID- 27003935 TI - Transposable Elements and Their KRAB-ZFP Controllers Regulate Gene Expression in Adult Tissues. AB - KRAB-containing zinc finger proteins (KRAB-ZFPs) are early embryonic controllers of transposable elements (TEs), which they repress with their cofactor KAP1 through histone and DNA methylation, a process thought to result in irreversible silencing. Using a target-centered functional screen, we matched murine TEs with their cognate KRAB-ZFP. We found the paralogs ZFP932 and Gm15446 to bind overlapping but distinguishable subsets of ERVK (endogenous retrovirus K), repress these elements in embryonic stem cells, and regulate secondarily the expression of neighboring genes. Most importantly, we uncovered that these KRAB ZFPs and KAP1 control TEs in adult tissues, in cell culture and in vivo, where they partner up to modulate cellular genes. Therefore, TEs and KRAB-ZFPs establish transcriptional networks that likely regulate not only development but also many physiological events. Given the high degree of species specificity of TEs and KRAB-ZFPs, these results have important implications for understanding the biology of higher vertebrates, including humans. PMID- 27003936 TI - Vascular Influence on Ventral Telencephalic Progenitors and Neocortical Interneuron Production. AB - The neocortex contains glutamatergic excitatory neurons and gamma-aminobutyric acid (GABA)ergic inhibitory interneurons. Extensive studies have revealed substantial insights into excitatory neuron production. However, our knowledge of the generation of GABAergic interneurons remains limited. Here we show that periventricular blood vessels selectively influence neocortical interneuron progenitor behavior and neurogenesis. Distinct from those in the dorsal telencephalon, radial glial progenitors (RGPs) in the ventral telencephalon responsible for producing neocortical interneurons progressively grow radial glial fibers anchored to periventricular vessels. This progenitor-vessel association is robust and actively maintained as RGPs undergo interkinetic nuclear migration and divide at the ventricular zone surface. Disruption of this association by selective removal of INTEGRIN beta1 in RGPs leads to a decrease in progenitor division, a loss of PARVALBUMIN and SOMATOSTATIN-expressing interneurons, and defective synaptic inhibition in the neocortex. These results highlight a prominent interaction between RGPs and periventricular vessels important for proper production and function of neocortical interneurons. PMID- 27003937 TI - Precise Editing of the Zebrafish Genome Made Simple and Efficient. AB - We present simple and efficient methods for creating heritable modifications of the zebrafish genome. Precisely modified alleles are generated by homologous recombination between the host genome and dsDNA donor molecules, stimulated by the induction of chromosomally targeted double-strand breaks. Several kilobase long tracts of genome sequence can be replaced. Tagging donor sequences with reporter genes that can be subsequently excised improves recovery of edited alleles by an order of magnitude and facilitates recovery of recessive and phenotypically silent conditional mutations. We generate and demonstrate functionality of (1) alleles with a single codon change, (2) an allele encoding an epitope-tagged version of an endogenous protein, (3) alleles expressing reporter proteins, and (4) a conditional allele in which an exon is flanked by recombinogenic loxP sites. Our methods make recovery of a broad range of genome editing events very practicable, significantly advancing applicability of the zebrafish for studying normal biological processes and modeling diseases. PMID- 27003938 TI - Multicolor Cell Barcoding Technology for Long-Term Surveillance of Epithelial Regeneration in Zebrafish. AB - Current fate mapping and imaging platforms are limited in their ability to capture dynamic behaviors of epithelial cells. To deconstruct regenerating adult epithelial tissue at single-cell resolution, we created a multicolor system, skinbow, that barcodes the superficial epithelial cell (SEC) population of zebrafish skin with dozens of distinguishable tags. With image analysis to directly segment and simultaneously track hundreds of SECs in vivo over entire surface lifetimes, we readily quantified the orchestration of cell emergence, growth, repositioning, and loss under homeostatic conditions and after exfoliation or appendage amputation. We employed skinbow-based imaging in conjunction with a live reporter of epithelial stem cell cycle activity and as an instrument to evaluate the effects of reactive oxygen species on SEC behavior during epithelial regeneration. Our findings introduce a platform for large scale, quantitative in vivo imaging of regenerating skin and reveal unanticipated collective dynamism in epithelial cell size, mobility, and interactions. PMID- 27003939 TI - Spatial Transcriptome for the Molecular Annotation of Lineage Fates and Cell Identity in Mid-gastrula Mouse Embryo. AB - Gastrulation of the mouse embryo entails progressive restriction of lineage potency and the organization of the lineage progenitors into a body plan. Here we performed a high-resolution RNA sequencing analysis on single mid-gastrulation mouse embryos to collate a spatial transcriptome that correlated with the regionalization of cell fates in the embryo. 3D rendition of the quantitative data enabled the visualization of the spatial pattern of all expressing genes in the epiblast in a digital whole-mount in situ format. The dataset also identified genes that (1) are co-expressed in a specific cell population, (2) display similar global pattern of expression, (3) have lineage markers, (4) mark domains of transcriptional and signaling activity associated with cell fates, and (5) can be used as zip codes for mapping the position of single cells isolated from the mid-gastrula stage embryo and the embryo-derived stem cells to the equivalent epiblast cells for delineating their prospective cell fates. PMID- 27003940 TI - 6-Hydroxydopamine-Induced Dopamine Reductions in the Nucleus Accumbens, but not the Medial Prefrontal Cortex, Impair Cincinnati Water Maze Egocentric and Morris Water Maze Allocentric Navigation in Male Sprague-Dawley Rats. AB - The nucleus accumbens (Nacc) and medial prefrontal cortex (mPFC) receive dopaminergic innervation from the ventral tegmental area and are involved in learning. Male rats with 6-hydroxydopamine (6-OHDA)-induced dopaminergic and noradrenergic reductions in the Nacc or mPFC were tested for allocentric and egocentric learning to determine their role in these forms of neuroplasticity. mPFC dopaminergic and noradrenergic reductions did not result in changes to either type of learning or memory. Nacc dopaminergic and noradrenergic reductions resulted in allocentric learning and memory deficits in the Morris water maze (MWM) on acquisition, reversal, and probe trials. MWM cued performance was also affected, but straight-channel swim times and swim speed during hidden platform trials in the MWM were not affected. Nacc dopaminergic and noradrenergic reductions also impaired egocentric learning in the Cincinnati water maze (CWM). Nacc-lesioned animals tested in the CWM in an alternate path through the maze were not significantly affected. 6-OHDA injections in the Nacc resulted in 63 % dopamine and 62 % norepinephrine reductions in the Nacc and 23 % reductions in adjacent dorsal striatum. 6-OHDA injections in the mPFC resulted in 88 % reductions in dopamine and 59 % reductions in norepinephrine. Hence, Nacc dopamine and/or norepinephrine play a role in egocentric and allocentric learning and memory, while mPFC dopamine and norepinephrine do not. PMID- 27003941 TI - Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice. AB - The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin 5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF 1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa. PMID- 27003942 TI - Intraoperative Magnetic Resonance Imaging for Pituitary Adenomas. AB - Surgery for pituitary adenomas attempts the optimally possible amount of tumor resection, which ideally is total excision. However, there are limitations in the resectability and in the intraoperative assessment of the radicality of an adenomectomy. Postoperative imaging is usually performed with a few months delay after tumor resection. Intraoperative magnetic resonance imaging (MRI) is used to depict the extent of tumor removal already achieved in the operating theater during surgery. To date, there are different low- and high-field intraoperative MRI systems available. Decompression of optic pathways, preservation of the pituitary and residual tumor can be largely predicted from the intraoperative images. Several studies convincingly show that intraoperative depiction of residual tumor allows targeted attack of the remnant. Not only is the amount of tumor resected increased, but also the percentage of total tumor excisions. Intraoperative MRI provides an immediate feedback to the surgeon and is thus a valuable quality control for pituitary surgery. It also allows the acquisition of data sets for precise intraoperative navigation. However, the MRI scanners are heavy and expensive and some systems even require extensive modification of the operating theater. Imaging slightly prolongs the operation but is not associated with an increased complication rate. There are also potential artifacts which must be considered. PMID- 27003943 TI - Impact of Registered Dietitian Expertise in Health Guidance for Weight Loss. AB - BACKGROUND & OBJECTIVES: Expertise of registered dietitians (RDs) is important for health guidance but has been poorly evaluated. We evaluated the kind of RD expertise that would improve their skills. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: This study was a post-hoc analysis of our randomized controlled trial, which compared the weight change between participants using the web-based self-disclosure health support and those using the email health support. Healthy men and women aged 35-64 years with a body mass index (BMI) of > = 24.5 kg/m2 were recruited for this study. We evaluated the relationship of RD expertise indicators including the duration of working as an RD, the experience of health counseling, and membership in the Japan Dietetic Association (JDA) with the weight loss of study participants. The primary endpoint was the change in body weight. Comparison of changes in body weight by the RD expertise indicators was evaluated using analysis of covariance. RESULTS: A total of 175 participants were eligible for analyses. Changes in body weight were significantly greater when they were supported by the RDs in the routine counseling group than when supported by the RDs in the non-routine counseling group (-1.8 kg versus -0.4 kg, fully adjusted P = 0.0089). Duration of working as an RD and JDA membership did not significantly affect changes in body weight. CONCLUSIONS: Among some indices of RD experience, the experience of providing routine experience of health counseling was associated with weight loss. PMID- 27003944 TI - Evaluation of the neutrophil-lymphocyte ratio in newly diagnosed nondiabetic hypertensive patients with ascending aortic dilatation. AB - BACKGROUND: Ascending aortic dilatation (AAD), more often encountered in hypertensive individuals compared with normotensive individuals, is an important cause of mortality in adults. Neutrophil-to-lymphocyte ratio (NLR), as an oxidative stress and proinflammatory marker, has recently emerged as a useful indicator to predict cardiovascular risk and adverse outcomes. The aim of our study was to investigate the relationship between NLR and AAD in patients with hypertension. METHODS: A total of 135 newly diagnosed and untreated hypertensive patients were enrolled in this study. Ninety-three consecutive hypertensive patients with AAD and 42 consecutive hypertensive patients with normal ascending aortic diameter were recruited into the study by comprehensive transthoracic echocardiography. NLR was calculated using the complete blood count. RESULTS: In the comparison of laboratory parameters between the hypertensive patients with AAD and hypertensive patients with normal ascending aortic diameter, NLR was found to be statistically significantly higher in the aortic dilatation group than in the control group (2.72+/-1.1 vs. 1.87+/-0.5, P<0.001). There was a statistically significant positive correlation between the ascending aortic diameter and NLR (r=0.524, P<0.001). According to multiple logistic regression analysis (ascending aortic diameter set as the dependent variable), smoking [odds ratio (OR): 1.57, 95% confidence interval (CI): 1.14-1.98, P=0.008], NLR (OR: 2.01, 95% CI: 1.57-3.25, P<0.001), and gamma-glutamyl transferase (OR: 1.98, 95% CI: 1.59-2.74, P=0.001) were found to be independent predictors of AAD. CONCLUSION: NLR as a marker of chronic low-grade inflammation may play a role in the pathogenesis of aneurysm of the ascending aorta in hypertensive patients. PMID- 27003945 TI - The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis. AB - BACKGROUND: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper extremity function. OBJECTIVE: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. METHODS: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm ( n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ?1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ?24 weeks apart and with a ?20% minimum threshold change for T25FW and 9HPT. RESULTS: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. CONCLUSION: The 24-week confirmed minimum worsening of ?20% for T25FW and 9HPT clearly separates SPMS progressors from non progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression. PMID- 27003946 TI - Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis. AB - BACKGROUND: The disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) vary in their mode of action and when therapies are changed, the consequences on inflammatory and degenerative processes are largely unknown. OBJECTIVE: We investigated the effect of switching from other DMTs to fingolimod on cerebrospinal fluid (CSF) biomarkers. METHODS: 43 RRMS patients were followed up after 4-12 months of fingolimod treatment. Concentrations of C-X C motif chemokine 13 (CXCL13), chemokine (C-C motif) ligand 2 (CCL2), chitinase-3 like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), neurofilament light protein (NFL), and neurogranin (NGRN) were analyzed by enzyme-linked immunosorbent assay (ELISA), while chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RESULTS: The levels of NFL, CXCL13, and CHI3L1 decreased ( p < 0.05) after fingolimod treatment. Subgroup analysis revealed a reduction in NFL ( p < 0.001), CXCL13 ( p = 0.001), CHI3L1 ( p < 0.001), and CHIT1 ( p = 0.002) in patients previously treated with first-line therapies. In contrast, the levels of all analyzed biomarkers were essentially unchanged in patients switching from natalizumab. CONCLUSION: We found reduced inflammatory activity (CXCL13, CHI3L1, and CHIT1) and reduced axonal damage (NFL) in patients switching from first-line DMTs to fingolimod. Biomarker levels in patients switching from natalizumab indicate similar effects on inflammatory and degenerative processes. The CSF biomarkers provide an additional measure of treatment efficacy. PMID- 27003947 TI - Th17 cells: A prognostic marker for MS rebound after natalizumab cessation? AB - BACKGROUND: Multiple sclerosis (MS) patients are at risk of renewed disease activity after discontinuing natalizumab (NAT) treatment. OBJECTIVE: Assessing the implication of T helper 17 (Th17) cells in MS reactivation after NAT cessation. METHODS: We monitored frequencies of Th17 cells and interleukin (IL) 17 cytokine levels in blood samples of 57 MS patients, without, during, and after NAT exposure. RESULTS: Frequencies of both Th17 cells and, in part, also IL-17 levels, in peripheral blood increased under prolonged NAT therapy, returned to baseline after NAT withdrawal and became almost undetectable in blood samples of individuals who experienced relapses during the wash-out phase. CONCLUSION: Assessing the Th17-cell/IL-17 axis might help to predict rebound MS activity after NAT withdrawal. PMID- 27003948 TI - Mental Fatigue: Impairment of Technical Performance in Small-Sided Soccer Games. AB - PURPOSE: To assess the effects of mental fatigue on physical and technical performance in small-sided soccer games. METHODS: Twenty soccer players (age 17.8 +/- 1.0 y, height 179 +/- 5 cm, body mass 72.4 +/- 6.8 kg, playing experience 8.3 +/- 1.4 y) from an Australian National Premier League soccer club volunteered to participate in this randomized crossover investigation. Participants played 15 min 5-vs-5 small-sided games (SSGs) without goalkeepers on 2 occasions separated by 1 wk. Before the SSG, 1 team watched a 30-min emotionally neutral documentary (control), while the other performed 30 min of a computer-based Stroop task (mental fatigue). Subjective ratings of mental and physical fatigue were recorded before and after treatment and after the SSG. Motivation was assessed before treatment and SSG; mental effort was assessed after treatment and SSG. Player activity profiles and heart rate (HR) were measured throughout the SSG, whereas ratings of perceived exertion (RPEs) were recorded before the SSG and immediately after each half. Video recordings of the SSG allowed for notational analysis of technical variables. RESULTS: Subjective ratings of mental fatigue and effort were higher after the Stroop task, whereas motivation for the upcoming SSG was similar between conditions. HR during the SSG was possibly higher in the control condition, whereas RPE was likely higher in the mental-fatigue condition. Mental fatigue had an unclear effect on most physical-performance variables but impaired most technical-performance variables. CONCLUSIONS: Mental fatigue impairs technical but not physical performance in small-sided soccer games. PMID- 27003949 TI - Production and Transport of Gaseous 18F-Synthons: 18F-Acyl Fluorides. AB - Fluorine-18 (18F, T 1/2=109.7 min) is a positron-emitting isotope that has found extensive application as a radiolabel for positron emission tomography (PET). Although gaseous 11C-CO2 and 11C-CH4 are practically transported from cyclotron to radiochemistry processes, 18F-fluoride is routinely transported in aqueous solution because it is commonly produced by proton irradiation of 18O-enriched water. In most cases, subsequent dry-down steps are necessary to prepare reactive 18F-fluoride for radiofluorination. In this work, a simple module was designed to generate gaseous 18F-acyl fluorides from aqueous 18F-fluoride solution by solid phase 18F-radiofluorination of acyl anhydride. The gaseous 18F-acyl fluorides were purified through a column containing Porapak Q/Na2SO4, resulting in high yields (>86%), purities (>99%) and specific activities (>1200 GBq/MUmol). Prototypic 18F-acetyl fluoride (18F-AcF) was readily transported through 15 m of 0.8 mm ID polypropylene tubing with low (0.64 +/- 0.12 %) adsorption to the tubing. Following dissolution of 18F-AcF in solvent containing base, highly reactive 18F-flouride was generated immediately and used directly for 18F labeling reactions. These data indicate that 18F-acyl fluorides represent a new paradigm for preparation and transport of anhydrous, reactive 18F-fluoride for radiofluorinations. PMID- 27003950 TI - Historical Overview of Transitional Feeding Recommendations and Vegetable Feeding Practices for Infants and Young Children. AB - Although recommendations for introducing solid foods to infants and young children have changed significantly since the beginning of the 20th century, vegetable consumption recommendations have always been an important part of the child-feeding repertoire. In 1958, the first report of the American Academy of Pediatrics (AAP) Committee on Nutrition stated that developmental maturity of the gut and neuromuscular system, growth rate, and activity level were good indicators for determining when to introduce solid foods to infants than age. All 7 editions of the AAP Pediatric Nutrition Handbook use an evidence-based model for recommendations concerning the complementary feeding of infants and young children. The model includes developmental readiness principles, feeding practices, and age-appropriate nutrient requirements. Dietary patterns and nutrient consumption among infants and young children have been analyzed using data from the 2002 and 2008 Feeding Infants and Toddlers Study (FITS). The 2008 FITS also collected information concerning participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Since 1972, WIC has been a cost-effective means of improving the diets and health of infants and young children from low-income families. Data from the 2008 FITS showed that many young children did not consume recommended amounts of fiber or potassium, and vegetable and fruit intakes continued to be lower than recommended. Low vegetable consumption and limited variety were also seen among WIC participants and nonparticipants aged 6 months to 4 years prior to changes in the WIC food package. Increasing children's consumption of all vegetables should continue to be a focus going forward. PMID- 27003951 TI - Efficient Syntheses of Vitamin K Chain-Shortened Acid Metabolites. AB - Vitamin K sequentially undergoes omega-oxidation followed by successive rounds of beta-oxidation to ultimately produce two chain-shortened carboxylic acid metabolites, vitamin K acid 1 and vitamin K acid 2. Two facile syntheses of these acid metabolites are described, each starting from commercially available menadione-cyclopentadiene adduct 3. Vitamin K acid 1 was synthesized in five steps via alkylation with a geranyl halide followed by subsequent oxidation reactions, while fully retaining the trans configuration of the side chain 2',3' double bond. Vitamin K acid 2 was synthesized in 5 steps from 3via alkylation with dimethylallyl chloride and subsequent oxidation reactions. PMID- 27003952 TI - Growing Up Before Their Time: The Early Adultification Experiences of Homeless Young People. PMID- 27003953 TI - Thermodynamic analysis of volatile organometallic fission products. AB - The ability to perform rapid separations in a post nuclear weapon detonation scenario is an important aspect of national security. In the past, separations of fission products have been performed using solvent extraction, precipitation, etc. The focus of this work is to explore the feasibility of using thermochromatography, a technique largely employed in superheavy element chemistry, to expedite the separation of fission products from fuel components. A series of fission product complexes were synthesized and the thermodynamic parameters were measured using TGA/DSC methods. Once measured, these parameters were used to predict their retention times using thermochromatography. PMID- 27003954 TI - Fukushima-derived radionuclides in sediments of the Japanese Pacific Ocean coast and various Japanese water samples (seawater, tap water, and coolant water of Fukushima Daiichi reactor unit 5). AB - We investigated Ocean sediments and seawater from inside the Fukushima exclusion zone and found radiocesium (134Cs and 137Cs) up to 800 Bq kg-1 as well as 90Sr up to 5.6 Bq kg-1. This is one of the first reports on radiostrontium in sea sediments from the Fukushima exclusion zone. Seawater exhibited contamination levels up to 5.3 Bq kg-1 radiocesium. Tap water from Tokyo from weeks after the accident exhibited detectable but harmless activities of radiocesium (well below the regulatory limit). Analysis of the Unit 5 reactor coolant (finding only 3H and even low 129I) leads to the conclusion that the purification techniques for reactor coolant employed at Fukushima Daiichi are very effective. PMID- 27003955 TI - 137Cs in the meat of wild boars: a comparison of the impacts of Chernobyl and Fukushima. AB - The impact of Chernobyl on the 137Cs activities found in wild boars in Europe, even in remote locations from the NPP, has been much greater than the impact of Fukushima on boars in Japan. Although there is great variability within the 137Cs concentrations throughout the wild boar populations, some boars in southern Germany in recent years exhibit higher activity concentrations (up to 10,000 Bq/kg and higher) than the highest 137Cs levels found in boars in the governmental food monitoring campaign (7900 Bq/kg) in Fukushima prefecture in Japan. The levels of radiocesium in boar appear to be more persistent than would be indicated by the constantly decreasing 137Cs inventory observed in the soil which points to a food source that is highly retentive to 137Cs contamination or to other radioecological anomalies that are not yet fully understood. PMID- 27003956 TI - Effective and ecological half-lives of 90Sr and 137Cs observed in wheat and rice in Japan. AB - Published pre-Fukushima food monitoring data from 1963 to 1995 were used to study the long-term presence of 137Cs and 90Sr in rice and wheat. Effective half-lives (Teff) were calculated for rice (137Cs: 5.6 years; 90Sr: 6.7 years) and wheat (137Cs: 3.5 years; 90Sr: 6.2 years), respectively. In rice, 137Cs exhibits a longer Teff because putrefaction processes will lead to the formation of NH4+ ions that are efficient ion exchangers for mineral-adsorbed cesium ions, hence making it more readily available to the plant. Knowledge on the long-term behavior of radiocesium and radiostrontium will be important for Japanese food safety campaigns after the Fukushima nuclear accident. PMID- 27003957 TI - Plutonium age dating (production date measurement) by inductively coupled plasma mass spectrometry. AB - This paper describes rapid methods for the determination of the production date (age dating) of plutonium (Pu) materials by inductively coupled plasma mass spectrometry (ICP-MS) for nuclear forensic and safeguards purposes. One of the presented methods is a rapid, direct measurement without chemical separation using 235U/239Pu and 236U/240Pu chronometers. The other method comprises a straightforward extraction chromatographic separation, followed by ICP-MS measurement for the 234U/238Pu, 235U/239Pu, 236U/240Pu and 238U/242Pu chronometers. Age dating results of two plutonium certified reference materials (SRM 946 and 947, currently distributed as NBL CRM 136 and 137) are in good agreement with the archive purification dates. PMID- 27003958 TI - Fast Marching Tree: a Fast Marching Sampling-Based Method for Optimal Motion Planning in Many Dimensions. AB - In this paper we present a novel probabilistic sampling-based motion planning algorithm called the Fast Marching Tree algorithm (FMT*). The algorithm is specifically aimed at solving complex motion planning problems in high dimensional configuration spaces. This algorithm is proven to be asymptotically optimal and is shown to converge to an optimal solution faster than its state-of the-art counterparts, chiefly PRM* and RRT*. The FMT* algorithm performs a "lazy" dynamic programming recursion on a predetermined number of probabilistically drawn samples to grow a tree of paths, which moves steadily outward in cost-to arrive space. As such, this algorithm combines features of both single-query algorithms (chiefly RRT) and multiple-query algorithms (chiefly PRM), and is reminiscent of the Fast Marching Method for the solution of Eikonal equations. As a departure from previous analysis approaches that are based on the notion of almost sure convergence, the FMT* algorithm is analyzed under the notion of convergence in probability: the extra mathematical flexibility of this approach allows for convergence rate bounds-the first in the field of optimal sampling based motion planning. Specifically, for a certain selection of tuning parameters and configuration spaces, we obtain a convergence rate bound of order O(n 1/d+rho), where n is the number of sampled points, d is the dimension of the configuration space, and rho is an arbitrarily small constant. We go on to demonstrate asymptotic optimality for a number of variations on FMT*, namely when the configuration space is sampled non-uniformly, when the cost is not arc length, and when connections are made based on the number of nearest neighbors instead of a fixed connection radius. Numerical experiments over a range of dimensions and obstacle configurations confirm our the-oretical and heuristic arguments by showing that FMT*, for a given execution time, returns substantially better solutions than either PRM* or RRT*, especially in high-dimensional configuration spaces and in scenarios where collision-checking is expensive. PMID- 27003959 TI - Influence of Twisting and Bending on the Jc and n-value of Multifilamentary MgB2 Strands. AB - The influences of strand twisting and bending (applied at room temperature) on the critical current densities, Jc , and n-values of MgB2 multifilamentary strands were evaluated at 4.2 K as function of applied field strength, B. Three types of MgB2 strand were evaluated: (i) advanced internal magnesium infiltration (AIMI)-processed strands with 18 filaments (AIMI-18), (ii) powder-in-tube (PIT) strands processed using a continuous tube forming and filling (CTFF) technique with 36 filaments (PIT-36) and (iii) CTFF processed PIT strands with 54 filaments (PIT-54). Transport measurements of Jc(B) and n-value at 4.2 K in fields of up to 10 T were made on: (i) PIT-54 after it was twisted (at room temperature) to twist pitch values, Lp , of 10-100 mm. Transport measurements of Jc(B) and n-value were performed at 4.2 K; (ii) PIT-36 and AIMI-18 after applying bending strains up to 0.6% at room temperature. PIT-54 twisted to pitches of 100 mm down to 10 mm exhibited no degradation in Jc(B) and only small changes in n-value. Both the Jc(B) and n-value of PIT-36 were seen to be tolerant to bending strain of up to 0.4%. On the other hand, AIMI-18 showed +/-10% changes in Jc(B) and significant scatter in n-value over the bending strain range of 0-0.6%. PMID- 27003960 TI - Precision editing the cells and engineering or re-engineering life, the era of geno-pharmacology/therapeutics has begun!! PMID- 27003961 TI - Vedolizumab: A novel anti-integrin drug for treatment of inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is the chronic inflammatory disorder of gastrointestinal tract consisting of two subtypes: Ulcerative colitis and Crohn's disease. IBD occurs due to infiltration of leukocytes in intestinal mucosa and derangements in intestinal barrier function. One of the most important steps in pathogenesis of IBD is the interactions between integrins on the surface of leukocyte. The alpha4beta7 integrin expressing T-cell is an important leukocyte involved in pathogenesis and represents a new drug target for the treatment of IBD. Vedolizumab is a humanized monoclonal antibody, which acts against alpha4beta7 integrin heterodimer and blocks the interaction of alpha4beta7 integrin with MAdCAM-1. It prevents leukocyte binding to endothelial surface and its extravasation into affected tissue. The efficacy and safety of the vedolizumab have been established in many clinical studies. It has shown promising results in various clinical studies where a greater percentage of patients as compared to a placebo achieved and maintained clinical response, clinical remission, and corticosteroid-free clinical remission. Vedolizumab has been shown to be well tolerated with slightly higher risk of infections, headache, naspharyngitis as compared to placebo. This review focuses on the potential role of vedolizumab for the treatment of IBD. PMID- 27003962 TI - Challenges and advances in optimizing liver allografts from donation after circulatory death donors. AB - In recent years, there has been a shift in the donor demographics with an increase in donation after circulatory death (DCD). Livers obtained from DCD donors are known to have poorer outcomes when compared to donors after brainstem death and currently only a small proportion of DCD livers are used. This review outlines the recent technological developments in liver DCD donation, including clinical studies using normothermic regional perfusion and extracorporal machine perfusion of livers from DCD donors. PMID- 27003963 TI - Pattern of burns identified in the Pediatrics Emergency Department at King Abdul Aziz Medical City: Riyadh. AB - OBJECTIVES: The objective of the study was to report the incidence of pediatric burn injuries and describe the pattern and the trend of pediatrics burns seen in King Abdul-Aziz Medical City. MATERIALS AND METHODS: Retrospective cross sectional study. Data collected through chart review of pediatrics patients aged 1-month to 14 years who presented with a burn injury to the pediatric emergency department during the year 2013. Burn patients were divided into two groups based on the percentage of total body surface area (TBSA) burned: Either <10% or more than 10%. Variables were compared between the two groups to identify the risk factors associated with more than 10% body surface area involvement. RESULTS: Burn incidence rate was 4.9 patients/1000/year. Children with burns on more than 10% TBSA accounted for 16% incidence (0.8/1000 emergency department patients). The burn injury severity ranged from 1% TBSA to 37%, with a mean of 5%. The proportion of male and female burn patients was 54.1% and 45.9%, respectively. Children between 1 and 3 years of age sustained the majority (48.6%) of burn injuries. Scald burns were found to be the most common cause of injury. Hot water and beverages were considered root for most of the scald burn injuries. As children advance in age, scald injury becomes less likely, and they are more obviously subjected to flame burn injuries. Burn injuries sustained at home were 35% compared to 2.7% occurring outside the home. None of the study variables were good predictors for severe burn injuries affecting more than 10% TBSA. CONCLUSION: The incidence and the severity of burn injuries remain high at the national level. Burn injuries continue to affect the pediatric population, predominantly, young children, which indicate the need for increasing parent educational programs and government regulations. Because we reported scald burns as the most common causes of burn injury, which are consistent with previous national reports, we recommend having legislation that focuses on scald burn prevention. PMID- 27003964 TI - High prevalence of multidrug-resistance uropathogenic Escherichia coli strains, Isfahan, Iran. AB - BACKGROUND AND OBJECTIVES: Urinary tract infection (UTI) is one of the most frequent infectious diseases and can occur in all age groups. Escherichia coli is the main cause of this infection. Multiple resistances to antimicrobial agents are increasing quickly in E. coli isolates and may complicate therapeutic strategies for UTI. The aim of this study was to determine the antibiotic resistance pattern and the multidrug-resistance (MDR) phenotypes in uropathogenic E. coli (UPEC). MATERIALS AND METHODS: A total of 135 UPEC isolates were collected from both outpatients (91 isolates) and inpatients (44 isolates) between September, 2012 and February, 2013. In order to determine the MDR among UPEC isolates, we have tested 15 antimicrobial agents and antibiotic susceptibility was done by Kirby-Bauer disk diffusion method. RESULTS: The percentage of MDR isolates (resistant to at least three drug classes such as aminoglycosides, fluoroquinolones, penicillins, cephalosporins, or carbapenems) was 68% in the inpatients and 61% in the outpatients. Antibiotic resistance to ampicillin, ceftazidim, nalidixic acid, and trimethoprim/sulfamethoxazole were higher than 50%. Amikacin, nitrofurantoin, and gentamicin showed markedly greater activity (89.1%, 85.9%, and 82.4% sensitivity, respectively) than other antimicrobial agents. Resistance to meropenem did show either in outpatients or in inpatients. INTERPRETATION AND CONCLUSIONS: The high prevalence of drug resistance among UTI patients calls for continuous monitoring of the incidence of drug resistance for appropriate empiric selection of antibiotic therapy. Empirical treatment of UTIs should be relied on susceptibility patterns from local studies. PMID- 27003965 TI - A hospital-based study on knowledge and attitude related to vitiligo among adults visiting a tertiary health facility of central India. AB - BACKGROUND: Vitiligo is one of the common stigmatizing dermatosis in the Indian society and the vitiligo patients have to face significant psychological hurt and social neglect. The severity of the stigma is related to the society's attitude and knowledge about it. AIMS AND OBJECTIVES: To document the prevalent knowledge and attitude in general public towards vitiligo patients, and to identify the determinants of good/poor knowledge and attitude. MATERIALS AND METHODS: A systematic random sampling technique was adopted to enroll 700 adult participants visiting an urban tertiary healthcare facility of central India. We developed a questionnaire to collect information on knowledge and attitude of the participants. A composite score was developed for good knowledge and attitude and performance of the participants was compared with the selected determinants. Data analysis was conducted by Stata software version 11. RESULTS: The overall knowledge score was good for 66.3% (95% confidence interval [CI]: 62.8%, 69.8%) of the participants. However, the score for attitude was comparatively poor i.e., only 16.9% (95% CI: 13.9%, 19.5%). None of the studied parameters could be significantly correlated with the knowledge score. Being married and being engaged in a health care related occupation were significant predictors of good attitude levels with P = 0.042 and 0.034 respectively, whereas female gender was the significant predictor for poor attitude with an odds ratio of 0.54 (95% CI: 0.33, 0.9) and P = 0.018. CONCLUSIONS: There were widespread myths prevalent about vitiligo in the studied population. The knowledge scores were better than attitude scores. PMID- 27003966 TI - Comparative study of frequency of micronuclei in normal, potentially malignant diseases and oral squamous cell carcinoma. AB - CONTEXT: The assessment of micronuclei (MN) in exfoliated oral epithelial cells is a promising tool for the study of epithelial carcinogens and can be used to detect chromosome breakage or mitotic interference, thought to be relevant to carcinogenesis. AIMS: To detect MN in exfoliated oral mucosal cells in individuals using various tobacco forms and also to detect frequency of MN in premalignant lesions and conditions (potentially malignant diseases [PMD's]) and oral squamous cell carcinoma (OSCC). To correlate frequency of MN in oral exfoliated cells in clinically diagnosed cases of OSCC followed by a histopathological grading. MATERIALS AND METHODS: A total of 90 subjects (30 smokeless tobacco users, 30 smokers and 30 nontobacco users) consisted of clinically diagnosed cases of PMD's and OSCC were selected for the study. Cytosmears from the groups were stained with rapid Papanicolaou stain. MN was identified according to the Tolbert et al. criteria. RESULTS: MN cells were found to be significantly higher in smokeless tobacco users than in smokers. The frequency of MN was three to four times higher in patients with OSCC as compared to patients in PMD's (P < 0.0001). The frequency of MN correlated with the histopathological grade was statistically significant. CONCLUSION: MN index can be used as a biomarker/screening test among the high-risk groups particularly the smokeless tobacco users and PMD's. MN can be a candidate to serve as a biomarker for prediction of the grade of OSCC. PMID- 27003967 TI - A retrospective study of the changing trends of antimicrobial resistance of Klebsiella pneumoniae isolated from urine samples over last 3 years (2012-2014). AB - BACKGROUND: In our country, the problem of antibiotic resistance is compounding because of overuse and misuse of antibiotics. There is no systematic national surveillance of antibiotic resistance and insufficient data are available to quantify the problem. OBJECTIVES: To study the changing pattern of antimicrobial resistance of Klebsiella pneumoniae isolates from patients of urinary tract infections over last 3 years. MATERIALS AND METHODS: A retrospective, record based study carried out based on the records culture sensitivity reports of indoor patients, during past 3 years (2012-2014). The type of organisms most common in urine sample was noted, and the drugs still effective for the particular organism were noted. RESULTS: Klebsiella was the second most frequent isolate throughout the 3 years (14%) of the total isolates). Analysis of the results year wise indicated that the lowest percentage of resistance was manifested against imipenem between 11.94% (2012) and 13.75% (2014). Over the successive years, resistance to ceftriaxone tends to increase from 74.95 % (2012) to 81% (2014). Klebsiella showed very high resistance 90.78% (2012) and 95.63% (2012) to co-trimoxazole and tetracycline, respectively with increasing trend to absolute resistance to both groups over the 3 years period. On an average over the 3 years Klebsiella showed a high amount of resistances to fluoroquinolones (72.71%) and aminoglycosides (76.22%). While multi-drug resistant Klebsiella range between 65% (2012) and 67% (2014). CONCLUSION: The antimicrobial resistance patterns are constantly evolving and vary from region to region it has become a necessity to do constant antimicrobial sensitivity surveillance. This will help clinicians to provide safe and effective empirical therapies. PMID- 27003968 TI - Study of fingerprint patterns to evaluate the role of dermatoglyphics in early detection of bronchial asthma. AB - BACKGROUND: Dermatoglyphics and bronchial asthma (BA) are both influenced by genetic factors. Hence, we assessed the diagnostic potential of correlation between fingerprint pattern and BA. MATERIALS AND METHODS: The study was carried out in out-patient Department of Pulmonary Medicine of All India Institute of Medical Sciences Bhopal. It included 36 patients of BA and 50 nonasthmatic individuals as controls. The following parameters were studied and analyzed: (a) Whorls, (b) arches, (c) radial loops, (d) ulnar loops, (e) the absolute finger ridge count (AFRC), (f) total finger ridge count (TFRC). RESULTS: A significant decrease in the mean value of the arches and increase in the mean value of the ulnar loops were observed in BA patients compared to the control group. The mean values of TFRC, AFRC, and whorls were similar in both groups. CONCLUSION: Evaluation of dermatoglyphic patterns may be useful in identifying patients prone to developing BA. PMID- 27003969 TI - Preventive (myoglobin, transferrin) and scavenging (superoxide dismutase, glutathione peroxidase) anti-oxidative properties of raw liquid extract of Morinda lucida leaf in the traditional treatment of Plasmodium infection. AB - BACKGROUND: Liquid extract of Morinda lucida leaf has been demonstrated to have antiplasmodial activities. Some phytochemicals act as preventive and or scavenging antioxidants. This study aimed to investigate the preventative and scavenging properties of the raw liquid extract of M. lucida leaf using plasma myoglobin, transferrin, superoxide dismutase (SOD), and glutathione (GSH) peroxidase. MATERIALS AND METHODS: Forty-eight Plasmodium-infected patients aged 29-47 years that have not been treated with any antimalaria medication but have decided to be treated traditionally using M. lucida leaf extract were recruited from 15 traditional homes in ATISBO, Saki-East, and Saki-West local government areas of Oke-Ogun - the Northern part of Oyo State-Nigeria. Identification of Plasmodium in the blood of the test and normal control subjects were carried out by Giemsha thick film technique. Packed cell volume, total bile acids, blood glucose, blood pressure, plasma myoglobin, transferrin, SOD, and GSH peroxidase (GPx) were evaluated in the normal control subjects and in the Plasmodium infected patients before and after the treatment with raw liquid extract of M. lucida leaf. RESULTS: A significant (P < 0.05) biochemical alterations were observed in the plasma values of transferrin, SOD, and GPx in the Plasmodium infected patients when compared with the normal control subjects and after treatment with the raw liquid extract of M. lucida leaf. CONCLUSION: Our study supports the possible preventative and scavenging antioxidative effect of the raw liquid extract of M. lucida leaf in the traditional treatment of Plasmodium infection. PMID- 27003970 TI - Effect of Iranian Ziziphus honey on growth of some foodborne pathogens. AB - BACKGROUND: Honey has previously been shown to have wound healing and antimicrobial properties, but this is dependent on the type of honey, geographical location, and flower from which the final product is derived. We tested the antimicrobial activity of a natural honey originating from the Ziziphus spina-christi tree, against selected strains of bacteria. Ziziphus honey among more than a 100 verities of honey is known to have the greatest value of energy and minerals in it. MATERIALS AND METHODS: The aim of this study was to determine the antibacterial activity of Ziziphus honey in 10%, 20%, 30%, and 40% dilutions (v/v) against Listeria monocytogenes, Salmonella typhimurium, Escherichia coli, and Staphylococcus aureus. Viable count enumeration of the sample was investigated after 0, 24, 72, and 120 h postinoculation with any of the bacteria using pour-plate method. RESULTS: The findings indicate that Ziziphus honey was effective against these pathogenic bacteria. In a comparative trial, antibacterial activity of Ziziphus honey was higher after 120 h incubation for each four bacteria in most dilutions. The microbial count showed 3-7.5 log reduction comparing with control after 120 h. CONCLUSIONS: Therefore, it is recommended using Ziziphus honey as a natural preservative and antibacterial agent. Also, it could potentially be used as therapeutic agents against bacterial infection particularly to the tested microorganisms. PMID- 27003971 TI - Evaluate the frequency distribution of nonadhesive virulence factors in carbapenemase-producing Acinetobacter baumannii isolated from clinical samples in Kermanshah. AB - BACKGROUND: Acinetobacter baumannii which is a Gram-negative bacterium can cause several different infections. The appearance of carbapenemase-producing A. baumannii in recent years has made the treatment process more difficult. The identification of virulence factors (VFs), such as nonadhesives in A. baumannii, helps to fight against related infections. MATERIALS AND METHODS: A total of 104 samples from teaching hospitals in Kermanshah, Iran, were collected during a 24 months period (2011-2013). Sample identification was first carried out by biochemical tests, and then their susceptibility to carbapenems was determined using the Kirby-Bauer method. For confirmation of carbapenemase-producing A. baumannii, polymerase chain reaction (PCR) was done for carbapenemase-encoding genes. In addition, the frequency of nonadhesive VFs in carbapenemase-producing isolates was determined by PCR. RESULTS: There were 50 isolates that were identified as carbapenemase-producing A. baumannii. The PCR results showed; 40 isolates (80%) for traT, 17 isolates (34%) for cvaC, and 8 isolates (16%) for iutA, and these encode serum resistance, colicin V and aerobactin, respectively. No significant correlation was observed between these three genes. CONCLUSIONS: The mechanism of A. baumannii virulence has always been in question. The role of VFs has also been recognized in other Gram-negative bacteria. According to the prevalence of traT, cvaC and iutA, as nonadhesive VFs, we can suggest that they could be the main mechanism of carbapenemase-producing A. baumannii pathogenesis. PMID- 27003972 TI - Metabolic syndrome in patients with severe mental illness in Gorgan. AB - BACKGROUND: Metabolic syndrome is commonly associated with cardiovascular diseases and psychiatric mental illness. Hence, we aimed to assess the metabolic syndrome among severe mental illness (SMI). MATERIALS AND METHODS: The study included 267 patients who were referred to the psychiatric unit at 5(th) Azar Education Hospital of Golestan University of Medical Sciences in Gorgan, Iran. RESULTS: The mean waist circumference, systolic and diastolic blood pressure, triglyceride and fasting blood glucose levels were significantly higher in the SMI with metabolic syndrome, but the high density lipoprotein (HDL)-cholesterol was significantly lower. The prevalence of metabolic syndrome in SMI patients was 20.60%. There were significant differences in the mean of waist circumference, systolic (except for women) and diastolic blood pressure, triglyceride, HDL cholesterol and fasting blood glucose in men and women with metabolic syndrome when compared with subjects without metabolic syndrome. The prevalence of metabolic syndrome in SMI women was higher than men. The most age distribution was in range of 30-39 years old. The most prevalence of metabolic syndrome was in age groups 50-59 years old. The prevalence of metabolic syndrome was increased from 30 to 59 years old. CONCLUSION: The prevalence of metabolic syndrome in patients with SMI in Gorgan is almost similar to those observed in Asian countries. The prevalence of metabolic syndrome was lower than western countries. These observations may be due to cultural differences in the region. It should be mention that the families of mental illness subjects in our country believe that their patients must be cared better than people without mental illness. These findings of this study suggest that mental illness patients are at risk of metabolic syndrome. According to our results, risk factors such as age and gender differences may play an important role in the presence of metabolic syndrome. In our country, women do less physical activity than men; therefore, the incidence of metabolic syndrome is higher among women. PMID- 27003973 TI - Effective factors in controlling diabetes progression among patients in the northwest of Iran. AB - BACKGROUND: Diabetes is the fifth leading cause of death in the world. Hence, we investigated the factors affecting disease control among diabetic patients referred to Imam Reza Hospital (central hospital in the Northwest of Iran). MATERIALS AND METHODS: One hundred and eight diabetic patients were evaluated. Patient's main medications including insulin, metformin, glibenclamide, and glytazon were registered and the levels of fasting blood sugar (FBS), glucose 2 h postprandial (pp), and hemoglobin A1c (HbA1c) were measured. All risk factors were evaluated by using a questionnaire completed by the patients. RESULTS: The average of HbA1c, FBS, and glucose 2 h pp was 7.33%, 159 mg/dl, and 233.03 mg/dl, respectively. In patients whose disease was controlled, the family history of the disease, the type of medication, and the visits to family physician had a significant association with disease control. The average mean of HbA1c among patients with controlled and uncontrolled disease was 5.93% and 8.63 % respectively. CONCLUSION: Less stress, education, and weekly exercise had an essential role in controlling the disease in diabetic patients from the Northwest of Iran and noncompliance with the prescribed diet by the physician and lack of timely medicine intake were the main reasons for uncontrolled disease. PMID- 27003974 TI - Hepatitis B virus and hepatitis C virus co-infection in hemodialysis patients: A retrospective study from a tertiary care hospital of North India. AB - BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent significant public health issues globally. They are important causes of morbidity and mortality in hemodialysis patients. Patients with HBV/HCV co infection have a higher risk of progression to cirrhosis and decompensated liver disease and have an increased risk of hepatocellular cancer (HCC). Because the two hepatotropic viruses share same modes of transmission, co-infection with the two viruses is not uncommon, especially in areas with a high prevalence of HCV infection and among people at high-risk for parenteral infection. AIMS: To estimate the prevalence of HBV and HCV co-infection among hemodialysis patients. MATERIALS AND METHODS: This retrospective, single centered hospital record-based study was carried out in a tertiary care hospital in Faridkot (Punjab), India. All the patients who underwent hemodialysis from January 2013 to December 2014 were included in the study. Patients of all age groups were tested for anti-HCV antibodies by fourth Generation HCV Tridot ELISA (J. Mitra & Co. Pvt. Ltd., New Delhi, India) and for hepatitis B surface antigen (HBsAg) by Hepalisa (J. Mitra & Co. Pvt. Ltd). RESULTS: Of the total 262 patients on hemodialysis, 88 (33.5%) were found to be having HCV infection, 4 (1.5%) were found to be positive for HBsAg. Co-infection with HBV/HCV was observed in 2 (0.8%) patients. Out of the total 92 patients having HBV and HCV infection, 62 (67.4%) were males and 30 (32.6%) were females. The majority of the patients were found to be of 41-60 years of age (41.3%) followed by 21-40 years (31.5%) and thereafter in 61-80 years (23.9%) and lowest prevalence was observed in the age group of <20 years (2.2%) and >80 years (1.1%). CONCLUSION: The risk of co-infection is greater among the chronic renal failure (CRF) patients due to the high frequency of transfusions of blood/blood products and extracorporeal circulation during hemodialysis. Patients with HBV/HCV co-infection have a higher risk of progression to cirrhosis and decompensated liver disease and further have an increased risk of HCC. In our study, out of the total 262 patients, 88 (33.5%) were found to be having HCV infection, 4 (1.5%) were found to be positive for HBsAg and dual infection was observed in 2 (0.8%) patients which is higher than the rates reported from different studies all over the world and India. PMID- 27003975 TI - Perceptions and knowledge toward mobile-health among the college going students in Coastal South India. AB - BACKGROUND: Among the manifold uses of mobile phones, mobile-health (mHealth) has been an important one, which is the practice of public health initiatives by awareness raising and communication campaigns. Optimum utilization of mHealth is possible only through adequate awareness. Hence, we aimed to study the perceptions and knowledge about mHealth among college going students in Mangalore, India. MATERIALS AND METHODS: A cross-sectional study was conducted in March 2014 among 627 students in selected engineering (302 students) and medical colleges (325 students) in Mangalore, India. Colleges were selected using convenience sampling (nonrandom) method. Data were collected using semi structured self-administered questionnaire and analyzed. RESULTS: Overall, 48.9% were males, 61.4% belonged to 18-20 years age group. The awareness about mobile phone health utilities among medical and engineering students was found to be similar. Among those who were aware of the concept of mHealth (74 [11.2%]), 40 (54.1%) were medical students. Marginally higher proportion of medical students felt mHealth could be helpful in protecting the patients' confidentiality and would help in better communication with the patients. CONCLUSION: There was high level of general awareness about mHealth among the subjects. However, many specific areas had limited knowledge among both the streams of students, hence highlighting the need for increasing awareness and sensitization. PMID- 27003976 TI - Subclinical hypothyroidism in pregnancy: An emerging problem in Southern West Bengal: A cross-sectional study. AB - BACKGROUND: Prevalence of subclinical hypothyroidism (SCH) in pregnancy varies widely in different parts of our country, but it has multiple adverse outcomes in both the mother and fetus. OBJECTIVES: This study was conducted to evaluate the prevalence of SCH in pregnant women during the first trimester and to identify the prevalence of thyroid autoimmunity in pregnant women. MATERIALS AND METHODS: This cross-sectional study (March 2014 to February 2015) was conducted among the pregnant women attending antenatal clinic in their first trimester at a tertiary care center. Morning samples of study participants were analyzed for free thyroxin (FT4), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab). Data expressed as mean +/- standard deviation and percentage (%) as applicable. RESULTS: Of the 510 subjects, 168 had TSH value >2.5 MUIU/ml (32.94%) with normal FT4 and they were diagnosed as SCH. TSH level >4.5 MUIU/ml was estimated in 13.92% (71) of the subjects. TPO Ab was positive in 57 (33.93%) of subclinical hypothyroid and 5 (1.47%) of normal subjects. 70.42% (50) of the subjects with TSH >4.5 MUIU/ml had positive TPO Ab. CONCLUSIONS: Prevalence of SCH is high in South Bengal and routine thyroid screening at the first antenatal visit should be done to reduce the social and financial burden caused by SCH. PMID- 27003977 TI - pH regulation of amphotericin B channels activity in the bilayer lipid membrane. AB - BACKGROUND: Amphotericin B (AmB) is a polyene antibiotic frequently applied in the treatment of systemic fungal infections in spite of its secondary effects. The pH plays a crucial role in modulating biophysical features of ion channels in the bilayer lipid membranes. AIM: In this study, the role of pH in the regulation of AmB channel was assessed by single channel recording of ion channel incorporated in the artificial membrane. MATERIALS AND METHODS: Bilayer lipid membrane was formed by phosphatidylcholine in a 350 MUm diameter aperture between two chambers, cis and trans contained 200/50 mMKCl solutions, respectively; then AmB was incorporated into the bilayer lipid membrane. Single channel recordings were used to indicate the effects of pH changes on AmB channels activity. The records were analyzed by Clamp fit 10 software. RESULTS: A kinetic analysis of single channel currents indicated a cation ion channel with 500 pS conductance and voltage-dependence of the open probability of the AmB channel (P o). A reduction of cis pH to 6 decreased P o and conductance. This effect was also voltage-dependent, being greater at a more positive above -40. The pH changes in the range of 6-8 had no effect on the reversal potential and ion selectivity. CONCLUSION: Our data indicated that extracellular acidity can reduce AmB activity. PMID- 27003978 TI - Azoospermia and testicular biopsy before intra-cytoplasmic sperm injection: Does the type of anesthesia make a difference? AB - AIM: Azoospermia is the most common form of male factor infertility, due to which sperms are retrieved for intra-cytoplasmic sperm injection (ICSI) under general or local anesthesia. The aim of the present study was to compare the efficacy of general and local anesthesia in an attempt to extract a sufficient quality of sperm for men with azoospermia, who intend to undergo ICSI. MATERIALS AND METHODS: A total number of 50 patients with azoospermia, who were within the age range of 20-40, were randomly scheduled for testicular sperm extraction with either general or local anesthesia before ICSI. The hormonal abnormalities and severe varicocele were evaluated and treated before the testicular sperm extraction. The inclusion criteria obliged the researchers to focus on men with azoospermic, those who were diagnosed by two semen analyses after a 3-day abstinence from coitus according to the modified WHO criteria, and 19< body mass index <=28. The concentration, motility, and morphology of the spermatozoa of the two groups were also compared. RESULTS: A total number of 76 men, with a mean age of 35.1 +/- 6.0, were selected, 26 were excluded from the study, and the remaining participants were randomly divided into two groups such as general anesthesia and lidocaine group. According to the results, the differences between the values of sperm parameters within various hours after the testicle biopsy were not statistically significant. Also, there was no significant difference between the two groups in terms of sperm motility and sperm morphology during various timing after the processing. CONCLUSION: The present study demonstrated that there was no evidence found for values of sperm parameters between the two groups, undergoing local and general anesthesia, within various hours after the testicular biopsy. Further investigations with more focus on concentration dependent lidocaine on human sperm parameters need to be carried out. PMID- 27003979 TI - Difference in described indications of medicines among drug information sources in India: An issue urgently to be addressed. AB - BACKGROUND: Drug information can be obtained from various sources such as National Formularies, drug package inserts (PI), other sources such as Monthly Index of Medical Specialities (MIMS), Current Index of Medical Specialities, and the information available with the regulators. Any variation in the information available in different sources can promote irrational drug use. In this study, we assessed this variation in a sample of commonly used drugs. MATERIALS AND METHODS: Fifty commonly used drugs were analyzed for any variation (both quantitative and qualitative) in information on indications as mentioned in commonly used drug information sources such as Central Drugs and Standards Control Organization (CDSCO) website, National Formulary of India (NFI), MIMS, and PI of medicines. RESULTS: We observed a variation in average number of indications per drugs given in CDSCO (2.2 +/- 0.25), NFI (3.51 +/- 0.42), MIMS (2.98 +/- 0.29), and PI (3.18 +/- 3.52). The CDSCO and NFI did not contain information about indication for 10 and 17 drugs, respectively, while MIMS and PI contained information about all the selected drugs. A subset analysis was done for 24 such drugs which were mentioned in all the four sources and it was found that NFI had listed the maximum number of indications per drug (3.79 +/- 0.53), followed by PI (3.08 +/- 0.44), MIMS (3.04 +/- 0.51), and CDSCO website (2.66 +/- 0.37) and this difference was found to be statistically significant (P = 0.02). We also observed some gross qualitative variation regarding drug information given in different sources. CONCLUSION: Variation exists in the quantity and quality of information available on indications about drugs available in various sources. Necessary steps need to be taken to harmonize drug information available across various sources so as to provide reliable and uniform drug information thereby promoting rational drug use. PMID- 27003980 TI - Rhinosporidiosis of lacrimal sac: An interesting case of orbital swelling. AB - Rhinosporidiosis is a chronic localized granulomatous disease caused by Rhinosporidium seeberi, an aquatic protistan parasite belonging to a clade, Mesomycetozoea. Infestation of Rhinosporidiosis to the eye and adnexa is termed oculosporidiosis, in such cases, conjunctival mucosa is mostly involved; however in our case, it involved only the lacrimal sac and deeper periorbital tissue and presented as a case of orbital swelling. Surgical excision of the lesion was done, postoperatively dapsone therapy was given for 6 months, and the patient responded very well with no recurrence till date. PMID- 27003981 TI - Mandibular lateral incisor with Vertucci Type IV root canal morphological system: A rare case report. AB - Abnormalities in the root canal anatomy are commonly occurring phenomenon. A thorough knowledge of root canal anatomy and its variation is necessary for successful completion of endodontic treatment. Mandibular anteriors are known for having extra canals. The role of genetics and racial variations may result in difference of incidence of root number and canal number. This paper attempts at explaining a rare case of successful endodontic management of two-rooted lateral incisor with awareness of data pertaining to number of canals, knowledge of canal morphology, correct radiographic interpretation, and tactile examination of canal wall which are important in detecting the presence of multiple canals. PMID- 27003982 TI - Unilateral conjunctivitis of unique etiology: A case report from Eastern India. AB - A middle-aged female patient from West Bengal presented with complaints of redness, foreign body sensation, and watering for 2 days in the left eye. Slit lamp examination of the left eye revealed several minute white foreign bodies moving over the bulbar conjunctiva. Removal of the foreign bodies under local anesthesia, followed by microscopic examination, suggested the presence of first instar larvae of Oestrus ovis; the sheep nasal bot fly. Diagnosis of unilateral external ophthalmomyiasis was made. Such cases though very infrequently have been reported in the past from Southern and Central Part of India. To the best of our knowledge, this is the second report from Eastern India. A high index of suspicion is necessary both on the part of the clinician and the microbiologist for correct diagnosis. PMID- 27003983 TI - Postendodontic restoration of severely decayed primary tooth using modified omega loop as a post. AB - The esthetic concern of severely mutilated primary anterior teeth in the case of early childhood caries has been a challenge to pediatric dentist. Early childhood caries is the most common chronic disease of the preschool child. The case report presented here is of a three year old boy with severely decayed maxillary anterior teeth. After root canal treatment, the primary maxillary central incisors were reinforced using modified omega post and followed by using celluloid strip crowns. The technique described here offers a simple and effective method for restoring severely decayed primary anterior teeth that reestablishes shape, function, and esthetics. PMID- 27003984 TI - Bilateral thalamic stroke due to occlusion of the artery of Percheron in a patient with a patent foramen ovale. AB - The artery of Percheron (AOP) is a rare vascular variant in which a single dominant thalamoperforating artery arises from the P1 segment and bifurcates to supply both paramedian thalami. Occlusion of this uncommon vessel results in a characteristic pattern of bilateral paramedian thalamic infarcts with or without mesencephalic infarctions. We report a case of a 37-year-old man with acute bilateral thalamic infarcts. The scans revealed symmetric bilateral hyperintense paramedian thalamic lesions consistent with an acute ischemic event. The posterior circulation was patent including the tip of the basilar artery and both posterior cerebral arteries, making the case compatible with occlusion of the AOP. This type of infarct is associated with embolic phenomena, and further evaluation revealed a patent foramen ovale as the source of emboli in the cerebrovascular circulation. The occlusion of the AOP is a rare cause of coma in young patients, and early recognition of this rare disease entity may lead to more favorable outcomes. PMID- 27003985 TI - Decoding of disinfection regime used in revascularization. PMID- 27003986 TI - Metastatic gastric cancer treatment: Second line and beyond. AB - Advanced gastric cancer (aGC), not amenable to curative surgery, is still a burdensome illness tormenting afflicted patients and their healthcare providers. Whereas combination chemotherapy has been shown to improve survival and tumor related symptoms in the frontline setting, second-line therapy (SLT) is subject to much debate in the scientific community, mainly because of the debilitating effects of GC, which would impede the administration of cytotoxic therapy. Recent data has provided sufficient evidence for the safe use of SLT in patients with an adequate performance status. Taxanes, Irinotecan and even some Fluoropyrimidine analogs were found to provide a survival advantage in this subset of patients. Most importantly, quality of life measures were also improved through the use of adequate therapy. Even more pertinent were the findings involving antiangiogenic agents, which would add measurable improvements without significantly jeopardizing the patients' well-being. Further lines of therapy are cause for much more debate nowadays, but specific targeted agents have shown considerable promise in this context. We herein review noteworthy published data involving the use of additional lines of the therapy after failure of standard frontline therapies in patients with aGC. PMID- 27003988 TI - Multidisciplinary management of nonfunctional neuroendocrine tumor of the pancreas. AB - Pancreatic neuroendocrine tumors (PNETs) are a rare and diverse group of tumors; nonfunctional (NF) PNETs account for the majority of cases. Most patients with NF PNETs have metastatic disease at the time of presentation. A variety of treatment modalities exist, including medical, liver directed, and surgical treatments. Aggressive surgical management is associated with prolonged survival, however available data are limited by selection bias and the frequent combination of PNETs with carcinoid tumors. Although few patients with metastatic disease will be cured, application of currently available therapies in a multidisciplinary setting can lead to excellent outcomes with prolonged patient survival. PMID- 27003987 TI - Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections. AB - Antibiotic-associated diarrhea (AAD) and Clostridium difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics. PMID- 27003989 TI - Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. AB - Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. PMID- 27003990 TI - Evidence-based medical oncology and interventional radiology paradigms for liver dominant colorectal cancer metastases. AB - Colorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharmacological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population. PMID- 27003991 TI - Vaccine against Helicobacter pylori: Inevitable approach. AB - Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium. PMID- 27003992 TI - Effective treatment of gastrointestinal bleeding with thalidomide--Chances and limitations. AB - For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibit angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely. PMID- 27003993 TI - Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype. AB - AIM: To study the hepatitis B virus (HBV) and hepatitis D virus (HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes. METHODS: We conducted a transversal study including 68 chronic hepatitis delta (CHD) (37 HIV-positive) patients and a control group of 49 chronic hepatitis B (CHB) (22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B (HBsAg) serum titers were analyzed with the Monolisa HBsAg Ultra system (Bio-Rad), using as quantification standard a serial dilution curve of an international HBsAg standard. Serum HBV-DNA titers were analyzed using the Roche Cobas TaqMan (Roche, Barcelona, Spain), and the serum HDV-RNA using an in house real-time qRT-PCR method, with TaqMan probes. HBV genotype was determined with the line immunoassay LiPA HBV genotyping system (Innogenetics, Ghent, Belgium). In those patients negative for LiPA assay, a nested PCR method of complete HBsAg coding region, followed by sequence analysis was applied. RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median (IQR): 1.25 (1.00-1.35) vs 2.95 (2.07-3.93) log10 (copies/mL), P = 0.013] and HIV positive patients [2.63 (1.24-2.69) vs 7.25 (4.61-7.55) log10 (copies/mL), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with LiPA assay. Finally, the HBsAg titers reflected no significant differences in CHD patients infected with HBV-A or D. CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E. PMID- 27003994 TI - Astragalus polysaccharide attenuates rat experimental colitis by inducing regulatory T cells in intestinal Peyer's patches. AB - AIM: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide (APS) against experimental colitis. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colitis was induced with 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The rats with colitis were treated with 400 mg/kg of APS for 7 d. The therapeutic effect was evaluated by colonic weight, weight index of the colon, colonic length, and macroscopic and histological scores. The levels of regulatory T (Treg) cells in Peyer's patches were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed using enzyme-linked immunosorbent assay. The expression of related orphan receptor-gammat (ROR-gammat), IL-23 and STAT-5a was measured by Western blot. RESULTS: After 7-d treatment with APS, the weight index of the colon, colonic weight, macroscopical and histological scores were decreased, while the colonic length was increased compared with the model group. The expression of interleukin (IL)-2, IL-6, IL-17, IL-23 and ROR-gammat in the colonic tissues was down-regulated, but Treg cells in Peyer's patches, TGF-beta and STAT5a in the colonic tissues were up-regulated. CONCLUSION: APS effectively ameliorates TNBS induced experimental colitis in rats, probably through restoring the number of Treg cells, and inhibiting IL-17 levels in Peyer's patches. PMID- 27003995 TI - Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway. AB - AIM: To investigate the apoptotic effects of melittin on SGC-7901 cells via activation of the mitochondrial signaling pathway in vitro. METHODS: SGC-7901 cells were stimulated by melittin, and its effect on proliferation and apoptosis of was investigated by methyl thiazolyl tetrazolium assay, morphologic structure with transmission electron microscopy, annexin-V/propidium iodide double-staining assay, measuring mitochondrial membrane potential (MMP) levels, and analyzing reactive oxygen species (ROS) concentrations were analyzed by flow cytometry. Cytochrome C (Cyt C), apoptosis-inducing factor (AIF), endonuclease G (Endo G), second mitochondria-derived activator of caspases (Smac)/direct IAP binding protein with low isoelectric point (Diablo), and FAS were analyzed by western blot. The expression of caspase-3 and caspase-8 was measured using activity assay kits. RESULTS: Melittin was incubated at 1.0, 2.0, 4.0, or 6.0 MUg/mL for 1, 2, 4, 6, or 8 h and showed a time- and concentration-dependent inhibition of SGC 7901 cell growth. Melittin induced SGC-7901 cell apoptosis, which was confirmed by typical morphological changes. Treatment with 4 MUg/mL melittin induced early apoptosis of SGC-7901 cells, and the early apoptosis rates were 39.97% +/- 3.19%, 59.27% +/- 3.94%, and 71.50% +/- 2.87% vs 32.63% +/- 2.75% for 1, 2, and 4 h vs 0 h (n = 3, P < 0.05); the ROS levels were 616.53% +/- 79.78%, 974.81% +/- 102.40%, and 1330.94% +/- 93.09% vs 603.74% +/- 71.99% (n = 3, P < 0.05); the MMP values were 2.07 +/- 0.05, 1.78 +/- 0.29, and 1.16 +/- 0.25 vs 2.55 +/- 0.42 (n = 3, P < 0.05); caspase-3 activity was significantly higher compared to the control (5492.3 +/- 321.1, 6562.0 +/- 381.3, and 8695.7 +/- 449.1 vs 2330.0 +/- 121.9), but the caspase activity of the non-tumor cell line L-O2 was not different from that of the control. With the addition of the caspase-3 inhibitor (Ac-DEVD-CHO), caspase-3 activity was significantly decreased compared to the control group (1067.0 +/- 132.5 U/g vs 8695.7 +/- 449.1 U/g). The expression of the Cyt C, Endo G, and AIF proteins in SGC-7901 cells was significantly higher than those in the control (P < 0.05), while the expression of the Smac/Diablo protein was significantly lower than the control group after melittin exposure (P < 0.01). Ac DEVD-CHO did not, however, have any effect on the expression of caspase-8 and FAS in the SGC-7901 cells. CONCLUSION: Melittin can induce apoptosis of human gastric cancer (GC) cells through the mitochondria pathways, and it may be a potent agent in the treatment of human GC. PMID- 27003996 TI - Predictors of re-bleeding after endoscopic hemostasis for delayed post-endoscopic sphincterotomy bleeding. AB - AIM: To predict the re-bleeding after endoscopic hemostasis for delayed post endoscopic sphincterotomy (ES) bleeding. METHODS: Over a 15-year period, data from 161 patients with delayed post-ES bleeding were retrospectively collected from a single medical center. To identify risk factors for re-bleeding after initial successful endoscopic hemostasis, parameters before, during and after the procedure of endoscopic retrograde cholangiopancreatography were analyzed. These included age, gender, blood biochemistry, co-morbidities, endoscopic diagnosis, presence of peri-ampullary diverticulum, occurrence of immediate post-ES bleeding, use of needle knife precut sphincterotomy, severity of delayed bleeding, endoscopic features on delayed bleeding, and type of endoscopic therapy. RESULTS: A total of 35 patients (21.7%) had re-bleeding after initial successful endoscopic hemostasis for delayed post-ES bleeding. Univariate analysis revealed that malignant biliary stricture, serum bilirubin level of greater than 10 mg/dL, initial bleeding severity, and bleeding diathesis were significant predictors of re-bleeding. By multivariate analysis, serum bilirubin level of greater than 10 mg/dL and initial bleeding severity remained significant predictors. Re-bleeding was controlled by endoscopic therapy in a single (n = 23) or multiple (range, 2-7; n = 6) sessions in 29 of the 35 patients (82.9%). Four patients required transarterial embolization and one went for surgery. These five patients had severe bleeding when delayed post-ES bleeding occurred. One patient with decompensated liver cirrhosis died from re-bleeding. CONCLUSION: Re-bleeding occurs in approximately one-fifth of patients after initial successful endoscopic hemostasis for delayed post-ES bleeding. Severity of initial bleeding and serum bilirubin level of greater than 10 mg/dL are predictors of re-bleeding. PMID- 27003997 TI - Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors? AB - AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis markers. METHODS: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-alpha, ER-alpha, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni's test, and Pearson's correlation test were applied for statistical analysis. RESULTS: ER-beta showed a progressive decline: normal tissue (23.5 +/- 4.9), LGD (21.1 +/- 4.8), HGD (9.3 +/- 3.5), AC (7.1 +/- 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 +/- 6.2). Conversely, ER-alpha showed a progressive increase from normal tissue (24.8 +/- 5.6) to AC (52.0 +/- 8.2); the expression in normal tissue was similar to controls (22.5 +/- 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson's correlation test showed a direct relationship between ER-beta and TUNEL LI (r = 0.8088, P < 0.0001). Conversely, ER-alpha was inversely correlated with TUNEL LI (r = - 0.7257, P < 0.0001). The co-expression of ER-beta and caspase 3 declined progressively from normal to neoplastic tissue. CONCLUSION: This study confirmed that ER-beta is strongly decreased in duodenal FAP carcinomas, declining in a multiple step fashion, thereby suggesting a putative anti-carcinogenic effect. ER alpha showed the opposite trend. ER-beta/caspase 3 co-expression suggests this hormone's possible involvement in apoptosis. Hormonal influences in FAP duodenal tumorigenesis, and modulation of these as a possible chemoprevention strategy, may be a promising approach. PMID- 27003998 TI - Comparison of hepatic venous pressure gradient and endoscopic grading of esophageal varices. AB - AIM: To determine the correlation between the hepatic venous pressure gradient and the endoscopic grade of esophageal varices. METHODS: From September 2009 to March 2013, a total of 176 measurements of hepatic venous pressure gradient (HVPG) were done in 146 patients. Each transjugular HVPG was measured twice, first using an end whole catheter (EH-HVPG), and then using a balloon catheter (B HVPG). The HVPG was compared with the endoscopic grade of esophageal varices (according to the general rules for recording endoscopic findings of esophagogastric varices), which was recorded within a month of the measurement of HVPG. RESULTS: The study included 110 men and 36 women, with a mean age of 56.1 years (range, 43-76 years). The technical success rate of the pressure measurements was 100% and there were no complication related to the procedures. Mean HVPG was 15.3 mmHg as measured using the end hole catheter method and 16.5 mmHg as measured using the balloon catheter method. Mean HVPG (both EH-HVPG and B HVPG) was not significantly different among patients with different characteristics, including sex and comorbid factors, except for cases with hepatocellular carcinoma (B-HVPG, P = 0.01; EH-HVPG, P = 0.02). Portal hypertension (> 12 mmHg HVPG) occurred in 66% of patients according to EH-HVPG and 83% of patients according to B-HVGP, and significantly correlated with Child's status (B-HVPG, P < 0.000; EH-HVGP, P < 0.000) and esophageal varies observed upon endoscopy (EH-HVGP, P = 0.003; B-HVGP, P = 0.006). One hundred and thirty-five endoscopies were performed, of which 15 showed normal findings, 27 showed grade 1 endoscopic esophageal varices, 49 showed grade 2 varices, and 44 showed grade 3 varices. When comparing endoscopic esophageal variceal grades and HVPG using univariate analysis, the P value was 0.004 for EH-HVPG and 0.002 for B HVPG. CONCLUSION: Both EH-HVPG and B-HVPG showed a positive correlation with the endoscopic grade of esophageal varices, with B-HVPG showing a stronger correlation than EH-HVPG. PMID- 27003999 TI - Is forceps more useful than visualization for measurement of colon polyp size? AB - AIM: To identify whether the forceps estimation is more useful than visual estimation in the measurement of colon polyp size. METHODS: We recorded colonoscopy video clips that included scenes visualizing the polyp and scenes using open biopsy forceps in association with the polyp, which were used for an exam. A total of 40 endoscopists from the Busan Ulsan Gyeongnam Intestinal Study Group Society (BIGS) participated in this study. Participants watched 40 pairs of video clips of the scenes for visual estimation and forceps estimation, and wrote down the estimated polyp size on the exam paper. When analyzing the results of the exam, we assessed inter-observer differences, diagnostic accuracy, and error range in the measurement of the polyp size. RESULTS: The overall intra-class correlation coefficients (ICC) of inter-observer agreement for forceps estimation and visual estimation were 0.804 (95%CI: 0.731-0.873, P < 0.001) and 0.743 (95%CI: 0.656-0.828, P < 0.001), respectively. The ICCs of each group for forceps estimation were higher than those for visual estimation (Beginner group, 0.761 vs 0.693; Expert group, 0.887 vs 0.840, respectively). The overall diagnostic accuracy for visual estimation was 0.639 and for forceps estimation was 0.754 (P < 0.001). In the beginner group and the expert group, the diagnostic accuracy for the forceps estimation was significantly higher than that of the visual estimation (Beginner group, 0.734 vs 0.613, P < 0.001; Expert group, 0.784 vs 0.680, P < 0.001, respectively). The overall error range for visual estimation and forceps estimation were 1.48 +/- 1.18 and 1.20 +/- 1.10, respectively (P < 0.001). The error ranges of each group for forceps estimation were significantly smaller than those for visual estimation (Beginner group, 1.38 +/- 1.08 vs 1.68 +/- 1.30, P < 0.001; Expert group, 1.12 +/- 1.11 vs 1.42 +/- 1.11, P < 0.001, respectively). CONCLUSION: Application of the open biopsy forceps method when measuring colon polyp size could help reduce inter-observer differences and error rates. PMID- 27004000 TI - Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients. AB - AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients. METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results. RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2(-DeltaCT) was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25(th) 3, 75(th) 10 vs 2, 25(th) 1, 75(th) 5) (P < 0.01). CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis. PMID- 27004001 TI - Negative short-term impact of intraoperative biliary lavage in patients with hepatolithiasis. AB - AIM: To evaluate short-term outcomes following intraoperative biliary lavage for hepatolithiasis. METHODS: A total of 932 patients who were admitted to the West China Medical Center of Sichuan University between January 2010 and January 2014 and underwent bile duct exploration and lithotomy were retrospectively included in our study. The patients were divided into the lavage group and the control group. Related pre-, intra-, and postoperative factors were recorded, analyzed, and compared between the two groups in order to verify the effects of biliary lavage on the short-term outcome of patients with hepatolithiasis. RESULTS: Amongst the patients who were included, 678 patients with hepatolithiasis were included in the lavage group, and the other 254 patients were enrolled in the control group. Data analyses revealed that preoperative baseline and related intraoperative variables were not significantly different. However, patients who underwent intraoperative biliary lavage had prolonged postoperative hospital stays (6.67 d vs 7.82 d, P = 0.024), higher hospitalization fees (RMB 28437.1 vs RMB 32264.2, P = 0.043), higher positive rates of bacterial cultures from blood (13.3% vs 25.8%, P = 0.001) and bile (23.6% vs 40.7%, P = 0.001) samples, and increased usage of advanced antibiotics (26.3% vs 38.2%, P = 0.001). In addition, in the lavage group, more patients had fever (> 37.5 degrees C, 81.4% vs 91.1%, P = 0.001) and hyperthermia (> 38.5 degrees C, 39.7% vs 54.9%, P = 0.001), and higher white blood cell counts within 7 d after the operation compared to the control group. CONCLUSION: Intraoperative biliary lavage might increase the risk of postoperative infection, while not significantly increasing gallstone removal rate. PMID- 27004002 TI - Application of gemstone spectral imaging for efficacy evaluation in hepatocellular carcinoma after transarterial chemoembolization. AB - AIM: To assess the value of gemstone spectral imaging (GSI) in efficacy evaluation in hepatocellular cancer (HCC) after transcatheter arterial chemoembolization (TACE) treatment. METHODS: Thirty patients with HCC underwent GSI, including nonenhanced, arterial, portalvenous and delayed phase scans, after TACE treatment. Arterial phase images were acquired with GSI for reconstruction of virtual nonenhanced images and color overlay images. Digital subtraction angiography (DSA) was performed in all these patients. Two blinded and independent readers evaluated the data in two reading sessions; standard nonenhanced, arterial, portalvenous, and delayed phase images were read in session A, and the optimal monochromatic images, iodine/water based images and spectrum features were read in session B. Sensitivity and specificity were calculated with the DSA data as the reference standard. The sensitivity and specificity were compared using the chi (2) test. RESULTS: DSA revealed 154 lesions in 30 patients, and 100 of them had blood supply. Overall sensitivity and specificity were 72% (72/100) and 77.8% (42/54) for session A, and 97% (97/100) and 94.4% (51/54) for session B, respectively. The sensitivity and specificity of the two reading sessions were significantly different (chi (2) = 23.04, chi (2) = 7.11, P < 0.05). CONCLUSION: Compared with conventional CT, GSI could significantly improve the detection of small and multiple lesions without increasing the radiation dose. Based on spectrum features, GSI could assess tumor homogeneity and more accurately identify residual tumors and recurrent or metastatic lesions during efficacy evaluation and follow-up in HCC after TACE treatment. PMID- 27004003 TI - Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors. AB - AIM: To determine the bowel symptoms associated with diabetes and diabetes related factors after excluding gastrointestinal (GI) organic diseases. METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre colonoscopy, 9 symptoms (borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank ordered logistic model adjusted for related confounders, and odds ratios (ORs) were estimated. RESULTS: In multivariate analysis, constipation [adjusted odds ratio (AOR) = 1.57, CI: 1.33-1.85, P < 0.01] and hard stools (AOR = 1.56, CI: 1.33-1.84, P < 0.01) were associated with diabetes, and fecal urgency (AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation (AOR = 1.16, CI: 1.00 1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good (mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with HbA1c >= 8.0% (AOR = 2.11, CI: 1.19-3.73), body mass index (BMI) < 25 (AOR = 2.11, CI: 1.22-3.66), and insulin use (AOR = 1.90, CI: 1.08 3.36); hard stools with diabetes duration (AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI < 25 (AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI < 25 (AOR = 2.60, CI: 1.52-4.43), serum creatinine level (AOR = 1.27, CI: 1.10-1.47), and insulin use (AOR = 1.92, CI: 1.09-3.38). CONCLUSION: Diabetes is associated with constipation, hard stools, fecal urgency, and incomplete evacuation, and poor glycemic control, duration, leanness, and nephropathy affect the risk of these symptoms. PMID- 27004004 TI - Clinical features, endoscopic polypectomy and STK11 gene mutation in a nine-month old Peutz-Jeghers syndrome Chinese infant. AB - AIM: To investigate multiple polyps in a Chinese Peutz-Jeghers syndrome (PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11 (STK11) gene analysis was also performed using a DNA sample from this infant. RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm * 2 cm in size, were removed from the infant's intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation (c.64_65het_delAT) in exon 1 in this PJS infant. CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS. PMID- 27004005 TI - Mutations in pre-core and basic core promoter regions of hepatitis B virus in chronic hepatitis B patients. AB - AIM: To investigate the frequency of mutations in pre-core (pre-C) and basic core promoter (BCP) regions of hepatitis B virus (HBV) from Shanxi Province, and the association between mutations and disease related indexes. METHODS: One hundred chronic hepatitis B patients treated at Shanxi Province Hospital of Traditional Chinese Medicine were included in this study. PCR-reverse dot blot hybridization and mismatch amplification mutation assay (MAMA)-PCR were used to detect the mutations in the HBV pre-C and BCP regions. HBV DNA content and liver function were compared between patients with mutant HBV pre-C and BCP loci and those with wild-type loci. The consistency between PCR-reverse dot blot hybridization and MAMA-PCR for detecting mutations in the HBV pre-C and BCP regions was assessed. RESULTS: Of the 100 serum samples detected, 9.38% had single mutations in the pre C region, 29.17% had single mutations in the BCP region, 41.67% had mutations in both BCP and pre-C regions, and 19.79% had wild-type loci. The rates of BCP and pre-C mutations were 65.7% and 34.3%, respectively, in hepatitis B e antigen (HBeAg) positive patients, and 84.6% and 96.2%, respectively, in HBeAg negative patients. The rate of pre-C mutations was significantly higher in HBeAg negative patients than in HBeAg positive patients (chi (2) = 26.62, P = 0.00), but there was no significant difference in the distribution of mutations in the BCP region between HBeAg positive and negative patients (chi (2) = 2.43, P = 0.12). The presence of mutations in the pre-C (Wilcoxon W = 1802.5, P = 0.00) and BCP regions (Wilcoxon W = 2906.5, P = 0.00) was more common in patients with low HBV DNA content. Both AST and GGT were significantly higher in patients with mutant pre-C and BCP loci than in those with wild-type loci (P < 0.05). PCR-reverse dot blot hybridization and MAMA-PCR for detection of mutations in the BCP and pre-C regions had good consistency, and the Kappa values obtained were 0.91 and 0.58, respectively. CONCLUSION: HBeAg negative patients tend to have HBV pre-C mutations. However, these mutations do not cause increased DNA copies, but associate with damage of liver function. PMID- 27004006 TI - Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: A prospective study. AB - AIM: To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with cirrhosis. METHODS: IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test. RESULTS: Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio > 0.07) compared to 4 (25%) healthy controls (P < 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival. CONCLUSION: Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study. PMID- 27004007 TI - Contained colonic perforation due to cecal retroflexion. AB - Complications of cecal retroflexion performed during colonoscopy have not previously been reported to occur. We report a case of contained colonic perforation secondary to using cecal retroflexion technique to examine the colon, and review available published reports of complications associated with this technique. We conclude that complications may rarely occur with use of cecal retroflexion, and that the clinical benefit of this technique is uncertain. PMID- 27004008 TI - Delayed diagnosis of alpha-1-antitrypsin deficiency following post-hepatectomy liver failure: A case report. AB - Post-hepatectomy liver failure (PHLF) is a leading cause of morbidity and mortality following major liver resection. The development of PHLF is dependent on the volume of the remaining liver tissue and hepatocyte function. Without effective pre-operative assessment, patients with undiagnosed liver disease could be at increased risk of PHLF. We report a case of a 60-year-old male patient with PHLF secondary to undiagnosed alpha-1-antitrypsin deficiency (AATD) following major liver resection. He initially presented with acute large bowel obstruction secondary to a colorectal adenocarcinoma, which had metastasized to the liver. There was no significant past medical history apart from mild chronic obstructive pulmonary disease. After colonic surgery and liver directed neo-adjuvant chemotherapy, he underwent a laparoscopic partially extended right hepatectomy and radio-frequency ablation. Post-operatively he developed PHLF. The cause of PHLF remained unknown, prompting re-analysis of the histology, which showed evidence of AATD. He subsequently developed progressive liver dysfunction, portal hypertension, and eventually an extensive parastomal bleed, which led to his death; this was ultimately due to a combination of AATD and chemotherapy. This case highlights that formal testing for AATD in all patients with a known history of chronic obstructive pulmonary disease, heavy smoking, or strong family history could help prevent the development of PHLF in patients undergoing major liver resection. PMID- 27004009 TI - Primary advanced esophago-gastric melanoma: A rare case. AB - Primary esophageal or gastric melanoma is a very rare disease with early metastasis. Due to its atypical symptom and less efficiency of chemotherapy and radiotherapy, the prognosis of esophageal or gastric melanoma is still very poor. Surgical resection remains the preferential treatment for esophageal or gastric melanoma. Here we present an extremely rare case of primary advanced esophago gastric melanoma. Debulking surgery was performed without chemotherapy or radiotherapy. However, abdominal recurrence and hepatic metastases were found within one month by a postoperative follow-up computed tomography. Three and a half months after surgical resection, the patient died of extensive abdominal metastasis. PMID- 27004010 TI - Liuweiwuling tablets protect against acetaminophen hepatotoxicity: What is the protective mechanism? AB - Study of the effects of natural products, including traditional Chinese Medicines, on acetaminophen hepatotoxicity has gained considerable popularity in recent years, and some of them showed positive results and even promising therapeutic potentials. A recent report suggested that Liuweiwuling tablets protect against acetaminophen hepatotoxicity and promote liver regeneration in a rodent model through alleviating the inflammatory response. However, several concerns exist regarding the limitations of the experimental design and interpretation of the data presented in this manuscript. PMID- 27004011 TI - Effect of competitive cues on reproductive morphology and behavioral plasticity in male fruitflies. AB - Phenotypic plasticity will be favored whenever there are significant fitness benefits of responding to environmental variation. The extent and nature of the plasticity that evolves depends on the rate of environmental fluctuations and the capacity to track and respond to that variability. Reproductive environments represent one arena in which changes can be rapid. The finding that males of many species show morphological, physiological, and behavioral plasticity in response to premating and postmating reproductive competition (RC) suggests that plasticity is broadly beneficial. The developmental environment is expected to accurately predict the average population level of RC but to be a relatively poor indicator of immediate RC at any particular mating. Therefore, we predict that manipulation of average RC during development should cause a response in plasticity "set" during development (e.g., size of adult reproductive structures), but not in flexible plasticity determined by the immediate adult environment (e.g., behavioral plasticity in mating duration). We tested this prediction in Drosophila melanogaster males by manipulating 2 independent cues of average RC during development: 1) larval density and 2) the presence or absence of adult males within larval culture vials. Consistent with the prediction, both manipulations resulted in the development of males with significantly larger adult accessory glands (although testis size decreased when males were added to culture vials). There was no effect on adult plasticity (mating duration, extended mating in response to rivals). The results suggest that males have evolved independent responses to long- and short-term variation in RC. PMID- 27004012 TI - Temperature can shape a cline in polyandry, but only genetic variation can sustain it over time. AB - Multiple mating by females (polyandry) is a widespread behavior occurring in diverse taxa, species, and populations. Polyandry can also vary widely within species, and individual populations, so that both monandrous and polyandrous females occur together. Genetic differences can explain some of this intraspecific variation in polyandry, but environmental factors are also likely to play a role. One environmental factor that influences many fundamental biological processes is temperature. Higher temperatures have been shown to directly increase remating in laboratory studies of insects. In the longer term, high temperature could also help to drive the evolution of larger-scale patterns of behavior by changing the context-dependent balance of costs and benefits of polyandry across environments. We examined the relative influence of rearing and mating temperatures on female remating in populations of Drosophila pseudoobscura that show a latitudinal cline in polyandry in nature, using a range of ecologically relevant temperatures. We found that females of all genotypes remated more at cooler temperatures, which fits with the observation of higher average frequencies of polyandry at higher latitudes in this species. However, the impact of temperature was outweighed by the strong genetic control of remating in females in this species. It is likely that genetic factors provide the primary explanation for the latitudinal cline in polyandry in this species. PMID- 27004013 TI - A lover or a fighter? Opposing sexual selection pressures on men's vocal pitch and facial hair. AB - The traditional assumption within the research literature on human sexually dimorphic traits has been that many sex differences have arisen from intersexual selection. More recently, however, there has been a shift toward the idea that many male features, including male lower-pitched voices and male beard growth, might have arisen predominantly through intrasexual selection: that is, to serve the purpose of male-male competition instead of mate attraction. In this study, using a unique set of video stimuli, we measured people's perceptions of the dominance and attractiveness of men who differ both in terms of voice pitch (4 levels from lower to higher pitched) and beard growth (4 levels from clean shaven to a month's hair growth). We found a nonlinear relationship between lower pitch and increased attractiveness; men's vocal attractiveness peaked at around 96 Hz. Beard growth had equivocal effects on attractiveness judgments. In contrast, perceptions of men's dominance simply increased with increasing masculinity (i.e., with lower-pitched voices and greater beard growth). Together, these results suggest that the optimal level of physical masculinity might differ depending on whether the outcome is social dominance or mate attraction. These dual selection pressures might maintain some of the documented variability in male physical and behavioral masculinity that we see today. PMID- 27004014 TI - An experimental conflict of interest between parasites reveals the mechanism of host manipulation. AB - Parasites can increase their host's predation susceptibility. It is a long standing puzzle, whether this is caused by host manipulation, an evolved strategy of the parasite, or by side effects due to, for example, the parasite consuming energy from its host thereby changing the host's trade-off between avoiding predation and foraging toward foraging. Here, we use sequential infection of three-spined sticklebacks with the cestode Schistocephalus solidus so that parasites have a conflict of interest over the direction of host manipulation. With true manipulation, the not yet infective parasite should reduce rather than enhance risk taking because predation would be fatal for its fitness; if host behavior is changed by a side effect, the 2 parasites would add their increase of predation risk because both drain energy. Our results support the latter hypothesis. In an additional experiment, we tested both infected and uninfected fish either starved or satiated. True host manipulation should act independently of the fish's hunger status and continue when energy drain is balanced through satiation. Starvation and satiation affect the risk averseness of infected sticklebacks similarly to that of uninfected starved and satiated ones. Increased energy drain rather than active host manipulation dominates behavioral changes of S. solidus-infected sticklebacks. PMID- 27004015 TI - "Parasite-induced aposematism" protects entomopathogenic nematode parasites against invertebrate enemies. AB - Aposematism is a well-known strategy in which prey defend themselves from predation by pairing defenses such as toxins, with warning signals that are often visually conspicuous color patterns. Here, we examine the possibility that aposematism can be induced in a host by colonies of infectious parasites in order to protect the parasites from the consequences of attacks on the host. Earlier studies show that avian predators are reluctant to feed on carcasses of host prey that are infected with the entomopathogenic nematode, Heterorhabditis bacteriophora. As the age of infection increases, the parasites kill and preserve the host and subsequently cause its color to change, becoming bright pink then red. Nematode colonies in dead hosts may also be vulnerable, however, to nocturnally active foragers that do not use vision in prey detection. Here, then we test a novel hypothesis that the nematode parasites also produce a warning odor, which functions to repel nocturnally active predators (in this case, the beetle Pterostichus madidus). We show that beetles decrease their feeding on infected insect prey as the age of infection increases and that olfactory cues associated with the infections are effective mechanisms for deterring beetle predation, even at very early stages of infection. We propose that "parasite induced aposematism" from the nematodes serves to replace the antipredator defenses of the recently killed host. Because sessile carcasses are exposed to a greater range of predators than the live hosts, several alternative defense mechanisms are required to protect the colony, hence aposematic signals are likely diverse in such "parasite-induced aposematism." PMID- 27004016 TI - Internest food sharing within wood ant colonies: resource redistribution behavior in a complex system. AB - Resource sharing is an important cooperative behavior in many animals. Sharing resources is particularly important in social insect societies, as division of labor often results in most individuals including, importantly, the reproductives, relying on other members of the colony to provide resources. Sharing resources between individuals is therefore fundamental to the success of social insects. Resource sharing is complicated if a colony inhabits several spatially separated nests, a nesting strategy common in many ant species. Resources must be shared not only between individuals in a single nest but also between nests. We investigated the behaviors facilitating resource redistribution between nests in a dispersed-nesting population of wood ant Formica lugubris. We marked ants, in the field, as they transported resources along the trails between nests of a colony, to investigate how the behavior of individual workers relates to colony-level resource exchange. We found that workers from a particular nest "forage" to other nests in the colony, treating them as food sources. Workers treating other nests as food sources means that simple, pre-existing foraging behaviors are used to move resources through a distributed system. It may be that this simple behavioral mechanism facilitates the evolution of this complex life history strategy. PMID- 27004017 TI - Does Mother-Child Interaction Mediate the Relation Between Maternal Depressive Symptoms and Children's Mental Health Problems? AB - The relation between maternal depressive symptoms and children's mental health problems has been well established. However, prior studies have predominantly focused on maternal reports of children's mental health problems and on parenting behavior, as a broad and unilateral concept. This cross-sectional study examined specific observed mother-child interaction behaviors through which maternal depressive symptoms are assumed to affect children's mental health problems. We expected higher rates of maternal depressive symptoms to predict higher rates of children's mental health problems, and we expected this relation to be mediated by low maternal warmth and high maternal psychological control. The sample consisted of 111 mother-child dyads referred for treatment. The mother-child interaction behaviors were coded according to the observed mother-child interaction tasks. Children's mental health problems were assessed using both maternal reports and children's self-reports. As expected, the results showed that maternal depressive symptoms were strongly related to maternal reports of children's internalizing and externalizing mental health problems. Surprisingly, maternal depressive symptoms were unrelated to children's self-reported depressive symptoms. Furthermore, mother-child interactions did not mediate the relation between maternal depressive symptoms and child mental health problems. Maternal depressive symptoms were associated with high maternal warmth, and high psychological control was associated with high levels of mother-reported externalizing mental health problems in children. These results partially replicate previous findings but add to these by using observational methods and multi-informant data. The importance of using a multi-informant and multi-method approach in assessing children's mental health problems in clinical practice and research are discussed. PMID- 27004018 TI - Understanding persistent bacterial lung infections: clinical implications informed by the biology of the microbiota and biofilms. AB - The infections found in chronic obstructive pulmonary disease, cystic fibrosis, and bronchiectasis share a number of clinical similarities, the most striking of which is bacterial persistence despite the use of antibiotics. These infections have been clinically described using culture-based methods usually performed on sputum samples, and treatment has been directed towards the bacteria found in this manner. Unfortunately the clinical response to antibiotics is frequently not predictable based on these cultures, and the role of these cultured organisms in disease progression has been debated. The past 20 years have seen a revolution in the techniques used to describe bacterial populations and their growth patterns. These techniques have revealed these persistent lung infections are vastly more complicated than described by traditional, and still widely relied upon, sputum cultures. A better understanding of the initiation and evolution of these infections, and better clinical tools to describe them, will dramatically alter the way patients are cared for. While clinical tests to more accurately describe these infections are not yet available, the better appreciation of these infections afforded by current science should enlighten practitioners as to the care of their patients with these diseases. PMID- 27004019 TI - Overview of food allergy diagnosis. AB - Food allergy is a condition with significant social and economic impact and a topic of intense concern for scientists and clinicians alike. Worldwide, over 220 million people suffer from some form of food allergy, but the number reported is just the tip of the iceberg. Recent years have brought new perspectives in diagnosing food allergy. Elucidating incriminated immunological mechanisms, along with drawing the clinical phenotype of food hypersensitivity reactions ensures an accurate diagnosis of food allergy. Moreover, molecular based allergy diagnosis, which is increasingly used in routine care, is a stepping-stone to improved management of food allergy patients. The aim of this review is to summarize the topic of IgE-mediated food allergy from the perspective of current diagnostic methods. PMID- 27004020 TI - The role of hormones in the pathogenesis of psoriasis vulgaris. AB - Psoriasis vulgaris is a chronic, common skin disease, which affects the patient's quality of life to the highest degree. Several exogenous factors and endogenous hormonal changes may act as triggers for psoriasis. The skin possesses a true endocrine system, which is very important in multiple systemic diseases. A number of conditions are associated with psoriasis, and its severity can also be influenced by hormones. Even though the sex hormones and prolactin have a major role in psoriasis pathogenicity, there are a lot of other hormones which can influence the psoriasis clinical manifestations: glucocorticoids, epinephrine, thyroid hormones, and insulin. PMID- 27004021 TI - Current Management of NAFLD. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. It affects about 1 billion individuals worldwide. While people with simple steatosis have no higher risk of death than the general population, people with non-alcoholic steatohepatitis are at increased risk of death compared to general population. Current management for NAFLD includes diet and lifestyle changes, management of underlying metabolic risk factors and pharmacological therapies. The objective of therapy is to prevent the complications. The problem with dietary and lifestyle interventions is that they are hard to implement. Compliance is the key. Until now, there is still no approved drug for the treatment of NAFLD. Insulin resistance is the main target of pharmacological therapy, but the question that we ask ourselves as physicians is who should receive medical treatment among NAFLD patients and for how long. PMID- 27004023 TI - The development of scientific reasoning in medical education: a psychological perspective. AB - Scientific reasoning has been studied from a variety of theoretical perspectives, which have tried to identify the underlying mechanisms responsible for the development of this particular cognitive process. Scientific reasoning has been defined as a problem-solving process that involves critical thinking in relation to content, procedural, and epistemic knowledge. The development of scientific reasoning in medical education was influenced by current paradigmatic trends, it could be traced along educational curriculum and followed cognitive processes. The purpose of the present review is to discuss the role of scientific reasoning in medical education and outline educational methods for its development. Current evidence suggests that medical education should foster a new ways of development of scientific reasoning, which include exploration of the complexity of scientific inquiry, and also take into consideration the heterogeneity of clinical cases found in practice. PMID- 27004022 TI - Hyaluronic acid as a biomarker of fibrosis in chronic liver diseases of different etiologies. AB - Chronic liver diseases represent a significant public health problem worldwide. The degree of liver fibrosis secondary to these diseases is important, because it is the main predictor of their evolution and prognosis. Hyaluronic acid is studied as a non-invasive marker of liver fibrosis in chronic liver diseases, in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of fibrosis. We review the advantages and limitations of hyaluronc acid, a biomarker, used to manage patients with chronic viral hepatitis B or C infection, non-alcoholic fatty liver disease, HIV-HCV coinfection, alcoholic liver disease, primary biliary cirrhosis, biliary atresia, hereditary hemochromatosis and cystic fibrosis. PMID- 27004025 TI - MicroRNAs as regulators of apoptosis mechanisms in cancer. AB - MicroRNAs or miRNAs are small non-coding RNAs that regulate gene expression. Their discovery has brought new knowledge in biological processes of cancer. Involvement of miRNAs in cancer development includes several major pathways from cell transformation to tumor cell development, metastasis and resistance to treatment. The first part of this review discusses miRNAs function in the intrinsic and extrinsic pathways of apoptosis. Due to the fact that many miRNAs that regulate apoptosis have been shown to play a major role in tumor cell resistance to treatment, in the second part of the review we aim at discussing miRNAs potential in becoming curative molecules. PMID- 27004024 TI - In vitro comparative models for canine and human breast cancers. AB - During the past four decades, an increased number of similarities between canine mammary tumors and human breast cancer have been reported: molecular, histological, morphological, clinical and epidemiological, which lead to comparative oncological studies. One of the most important goals in human and veterinary oncology is to discover potential molecular biomarkers that could detect breast cancer in an early stage and to develop new effective therapies. Recently, cancer cell lines have successfully been used as an in vitro model to study the biology of cancer, to investigate molecular pathways and to test the efficiency of anticancer drugs. Moreover, establishment of an experimental animal model for the study of human breast cancer will improve testing potential anti cancer therapies and the discovery of effective therapeutic schemes suitable for human clinical trials. In this review, we collected data from previous studies that strengthen the value of canine mammary cancer cell lines as an in vitro model for the study of human breast cancer. PMID- 27004026 TI - Neuroimaging in pediatric phakomatoses. An educational review. AB - Phakomatoses are a group of more than 30 entities with an inheritance pattern that primarily affects the central nervous system, skin, viscera and connective tissue. The aim of this paper is to make an educational review of the most common radiological findings on phakomatoses through the iconography of the cases collected in our magnetic resonance imaging (MRI) and computer tomography (CT) units over the last ten years. Also, we describe and illustrate by these techniques the main features of the most common entities within the wide spectrum of diseases. As highly variable and age dependent, imaging techniques have an important role in the diagnosis and follow-up of these patients. Increased awareness for the need to implement and conduct screening programs could be considered as a solution to prevent late diagnosis and to treat the patients in early stages of disease. PMID- 27004027 TI - Better prognosis in overweight/obese coronary heart disease patients with high plasma levels of leptin. AB - BACKGROUND AND AIM: The involvement of leptin in atherosclerosis is very complex, including inflammation, the oxidative stress and thrombosis. Leptin has atherogenic and also antiatherogenic actions. In obesity elevated leptin levels are not sufficient to prevent disturbances of energy balance, suggesting that obese people are leptin resistant. The aim of the study was to investigate the relationship between baseline plasma levels of leptin and the incidence of new ischemic events in patients with CHD. METHODS: Plasma levels of leptin in fifty nine consecutive patients (29 men and 30 women) with CHD hospitalized in the County Emergency Clinical Hospital of Cluj-Napoca were measured using commercially available ELISA at admission. Patients with active infectious disease, neoplasia, acute coronary syndrome, stroke, hepatic or renal failure and severe heart failure were excluded The relationship between leptin levels and incident cardiovascular events (angina, nonfatal myocardial infarction or heart failure) over two years follow-up was studied using MEDCALC version 9.6. RESULTS: 73.6% patients with CHD were overweight or suffered of obesity. There were no significant differences between women and men regarding the plasma levels of leptin, the body mass index (BMI), the number of rehospitalizations, rehospitalizations/patient, diabetes mellitus, hypertension or dyslipidemia. Only in women plasma levels of leptin are correlated with BMI. As compared with men with overweight and obesity (BMI>=25kg/m(2)), plasma levels of leptin were significantly higher in women with overweight and obesity (3905.97+/-463.91 pg/ml vs 1835.17+/-533.9 pg/ml) (p<0.002). Patient gender could not be demonstrated to influence prognosis. During the two years we recorded one or more readmissions in 26 patients (44%). The analysis of time till readmission using Kaplan-Meier curves, showed that leptin level (cut-off 2000 pg/ml, HR 0.38, 95% CI 0.17-0.83; p=0.01) and BMI (cut-off 28 kg/m(2), HR 0.3164, 95% CI 0.145-0.0689; p<0.01) were significantly associated with prognosis. CONCLUSION: Patients with plasma levels of leptin >2000 pg/ml and BMI >28kg/m(2) had a better prognosis, suggesting a protective role of leptin in overweight/mild obesity. PMID- 27004028 TI - Vitis vinifera seeds extract for the modulation of cytosolic factors BAX-alpha and NF-kB involved in UVB-induced oxidative stress and apoptosis of human skin cells. AB - BACKGROUND AND AIMS: The depletion of the ozone layer allows overexposure of the skin to UV radiation, which is prolonged due to the increasing life expectancy, together with inappropriate life habits contribute to the increasing incidence of cutaneous malignancies. Plant extracts with antioxidant capacities are frequently employed as a means to protect skin against ultraviolet (UV) radiations, thus preventing skin cancers. In the present study we assessed a red grape seed extract (GSE) potential capacities to reduce ultraviolet B (UVB) radiation induced reactive oxygen species (ROS) and subsequent apoptosis in a human keratinocytes cell line (HaCaT). We identified molecules and pathways modulated by the GSE through which this may exert its photoprotective effect. METHODS: The GSE was standardized according to its polyphenolic content and the most important biologically active compounds, such as epigallocatechin and epicatechin, catechin hydrate, procyanidin B and gallic acid were evidenced by high-performance liquid chromatography. According to the plant extract cytotoxicity on the HaCaT cell line, two concentrations were selected for testing from the non-toxic range: GSE1 (37.5 MUgEqGA/ml) and GSE2 (75 MUgEqGA/ml). The level of ROS was evaluated with CM-H2DCFDA assay, while apoptosis, Bax-alpha and NF-kbeta p65 proteins with ELISA and confirmed by western-blot. RESULTS: Both concentrations of the extract decreased the level of ROS in UVB-irradiated keratinocytes (p<0.001), whereas apoptosis and Bax-alpha pro-apoptotic protein were only reduced by the higher concentration (GSE2). The NF-kB p65 protein level registered increasing values in time after UVB exposure of the cells, while the tested plant extract re established its level when its smaller concentration was used (GSE1). CONCLUSION: These results encourage further studies on this extract in order to identify other molecules and pathways through which this extract might exert its beneficial effects and also recommend its use as a potential photoprotective agent. PMID- 27004029 TI - Prevalence and predictors of non-alcoholic fatty liver disease as defined by the fatty liver index in a type 2 diabetes population. AB - BACKGROUND AND AIMS: We aimed to study the prevalence and the predictive factors of non-alcoholic fatty liver disease (NAFLD) defined by the fatty liver index (FLI) in type 2 diabetic patients (T2DM). METHODS: Three hundred and eighty-one T2DM outpatients who regularly attended a Consulting Clinic in Cluj were retrospectivelly included. FLI, a surrogate steatosis biomarker based on body mass index (BMI), waist circumference (WC), triglycerides (TGL) and gammaglutamyl transferase (GGT) was used to assess NAFLD in all patients. Anthropometric and biochemical parameters were measured. Hepatic steatosis (HS) was evaluated by ultrasonography. RESULTS: NAFLD-FLI (defined as FLI>60) was correlated with HS evaluated by ultrasound (r=0.28; p<0.001). NAFLD-FLI was detected in 79% of T2DM. The prevalence of obesity in NAFLD-FLI patients was 80%. Of the patients with normal alanine aminotransferase (ALAT), 73.8 % had NAFLD. At univariate analysis, NAFLD-FLI was correlated with age (r= -0.14; p=0.007), sex (r=0.20; p<0.001), LDL cholesterol (r=0.12; p=0.032), HDL cholesterol (r = -0.13; p=0.015), ALAT (r=0.20; p<0.001) and ASAT (r=0.19; p<0.001). At multiple regression analysis, sex, ALAT and LDL-cholesterol were independent predictors of NAFLD-FLI. After logistic regression model, ALAT, LDL-cholesterol, HOMA-IR were good independent predictors of NAFLD-FLI. CONCLUSIONS: NAFLD-FLI could be useful to identify NAFLD in T2DM patients. Subjects with T2DM had a high prevalence of NADLD-FLI even with normal ALAT levels. Our findings showed that sex, ALAT, LDL cholesterol and IR were significant and independent factors associated with the presence of NAFLD in T2DM subjects. PMID- 27004030 TI - XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population. AB - BACKGROUND AND AIMS: Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. METHODS: We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. CONCLUSION: In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group. PMID- 27004031 TI - Mineral and bone disorders, morbidity and mortality in end-stage renal failure patients on chronic dialysis. AB - BACKGROUND AND AIM: In spite of numerous interventions, the control of mineral disturbances remains poor in end-stage renal failure (ESRF) patients. Chronic kidney disease - mineral and bone disorders (CKD-MBD) represent an important cause of mortality and morbidity. The aim of this study is to analyze the relationship between mineral and bone disorders (MBD) and their components impact on all-cause mortality and cardiovascular (CDV) mortality and morbidity in chronic dialysis patients. METHODS: This prospective study was carried out in a cohort of 92 randomly selected patients with ESRF treated with hemodialysis (HD) and peritoneal dialysis (PD). The data regarding demographic and clinical characteristics were recorded, including vascular disease (coronary, cerebral, peripheral). The follow-up lasted 40 months and the final evaluation included the number and causes of deaths, CDV events and disease. Serum Ca, P, ALP, iPTH, albumin, cholesterol, urea and creatinine levels were measured. The plain radiographic films of hands and pelvis evaluated all bone abnormalities suggestive of renal osteodystrophy (ROD) and peripheral vascular calcification (VC). RESULTS: All-cause annual mortality represented 9.25% in HD and 9.09% in PD patients. The CDV mortality represented almost 44% in HD patients and 66% in PD patients from all deaths. There was a high prevalence of CDV diseases and events. High and low serum P levels were associated with a worse survival rate. Hypercalcaemia was associated with high risk for CDV events in HD patients. In PD patients, the relationship between increased ALP levels and all-cause mortality was significant. Other mineral markers were not predictive of the outcome in the studied patients. In the HD patients the severity of VC was associated with all cause and CDV mortality, and with CDV events. Male gender, hypercholesterolemia, decreased URR, albumin and creatinine were identified as risk factors for all cause mortality. The diabetics had higher death rates. Low dialysis efficacy represented a risk factor for mortality and CDV diseases and events. In PD patients, low albumin induced a higher death rate. In PD patients the death rate was similar to HD patients. CONCLUSION: All-cause mortality was higher than in general population, but lower than the chronic dialysis patients' mortality reported in other studies. The death rates in HD and PD patients were similar. VC and serum P levels influenced the outcome in the HD patients - increased the risk for all-cause and CDV mortality, but also for CDV events. ALP levels influenced outcome in PD patients. There were no significant differences between HD and PD patients regarding outcome. PMID- 27004032 TI - Synergistic Effects Induced by Combined Treatments of Aqueous Extract of Propolis and Venom. AB - BACKGROUND AND AIMS: Breast cancer is a heterogeneous disease and the leading cause of cancer mortality worldwide. Triple negative breast cancer (TNBC) is considered to be one of the most aggressive breast neoplasia due to failure of chemotherapy response. Thus, there is an urgent need of finding alternative therapies for TNBC. This study was designed to evaluate the synergistic effect induced by propolis and bee venom on luminal (MCF-7) and TNBC (Hs578T) cell lines. METHODS: In order to evaluate the synergistic effect of aqueous extract of propolis and bee venom, we treated in combination two breast cancer cell lines: MCF-7(luminal subtype) and Hs578T (TNBC subtype). RESULTS: Our results indicate that both cell lines exhibited similar sensitivity to the aqueous extract of propolis at a dilution of 0.072-0.09 mg/ml. The results concerning IC50 for bee venom on MCF-7 cells was 1 mg/ml, 20 times higher than 0.05 mg/ml in Hs578T cells. By combining the aqueous extract of propolis with bee venom, we obtained synergistic effects at a higher concentration, which was 5 and 2 times stronger than the two treatments alone. CONCLUSION: Overall, the results from our study indicated that the combination of aqueous extract of propolis and bee venom treatments induced synergistic antiproliferative effects in a concentration dependent manner in breast cancer cells. Thus we can hypothesize that the combination of honeybee propolis and venom might be involved in signaling pathways that could overcome cells resistance to therapy. PMID- 27004033 TI - Cost-Efficiency Analysis of a Multi-Pavilion Hospital in Cluj County. AB - BACKGROUND AND AIM: Multi-hospital health systems have become the most popular administrative structure in healthcare, leading to both opportunities and challenges for hospital administrators. In government-funded healthcare systems, there is a balance between costs and the provision of health services. The aim of the present study is to assess the efficiency in terms of costs of a multi pavilion hospital from Cluj County, Romania. METHODS: The institution analyzed in this article is the Adults' Clinical Hospital in Cluj-Napoca. A descriptive retrospective study collected data from January 2004 to December 2010. A set of indicators were compiled, divided into three main categories: personnel, statistics, and financial. RESULTS: Twenty-one financial indicators were investigated. Heterogeneity between different years was observed for the continuous hospitalization indicator and the wage budget indicator. The highest variability was observed between the budget and expenses indicators, while a smaller variability was observed at the average costs per patient. The costs per patient have increased at all pavilions in the studied time frame, the higher costs being at the Internal Medicine and Surgery pavilions: 10,203 RON in 2010 (1 euro ~ 4.4 RON). CONCLUSION: The pavilions included in the Adults' Clinical Hospital Cluj-Napoca have different expenses patterns, as each pavilion is focused on different specialties. Each pavilion serves different target groups, requiring different procedures. This in turn results in different expense patterns across each pavilion. PMID- 27004034 TI - Reconstruction of the Abdominal Wall in Anatomical Plans. Pre- and Postoperative Keys in Repairing "Cold" Incisional Hernias. AB - BACKGROUND AND AIMS: The clinical results of the vertical "vest-over-pants" Mayo repair were evaluated, and the risk factors for incisional hernia recurrence were studied. The purpose of this study is to point out the importance of reducing pre and post operative risk factors in the incisional hernia repair process in order to achieve a physiologically normal abdominal wall. METHODS: Twenty patients diagnosed with incisional hernia underwent an abdominal reconstruction procedure using the Mayo (Paletot) technique at Bichat Claude Bernard Hospital between 2005 and 2015. All procedures were performed by a single surgeon and all patients were pre-operatively prepared, identifying all coexisting conditions and treating them accordingly before undergoing surgery. RESULTS: All patients underwent at least one surgical operation before the hernia repair procedure and a quarter had experienced at least three, prior to this one. Nine patients had a body mass index of >30 kg/m2. Additional risk factors and comorbidities included obesity in 45%, diabetes mellitus in 10%, smoking in 55%, and high blood pressure in 40%. Hernia defect width was from 3 cm (25% F) to 15 cm (5% M) of which nine patients (45%) had a 10 cm defect. Most of the patients had an average hospitalization of 7 days. The patients were carefully monitored and were called on periodic consultations after 3, 6, and 12 months from the moment of the procedure. Patient feedback regarding hernia recurrence and complaints about the scar were noted. Physical examination is essential in determining the hernia recurrence therefore the scar was examined for any abnormalities that may have occurred, which was defined as any palpable or detected fascial defect located within seven centimeters of the hernia repair. Post-operative complications: seroma formation, wound hematoma, superficial and deep wound infection, recurrences and chronic pain were followed and no complications were registered during the follow-up period. CONCLUSIONS: Reducing the risk factors to a minimum prior to surgery will increase the success of the incisional hernia repair and generate a positive impact on the patient's quality of life. The lofty goal of significant weight loss prior to elective hernia has shown to be the key factor in using the Mayo technique for incisional hernia repair. This study demonstrates that the Mayo repair technique is a suitable and trustworthy alternative for repairing incisional hernias with very good results. It's costs are minimal and it can be easily reproduced, even by less experienced surgeons. PMID- 27004035 TI - Development of new 5-(chromene-3-yl)methylene-2,4-thiazolidinediones as antimicrobial agents. AB - BACKGROUND AND AIMS: In the context of the increasing phenomenon of microbial resistance to usual drugs, the development of new treatment strategies and new therapeutic protocols is a constant need. Thiazolidinedione and chromone represent two important scaffolds in medicinal chemistry due to their large pharmacological applicability. METHODS: We synthesized a new 5-(chromene-3 yl)methylene-2,4-thiazolidinedione starting from 6,8-dichloro-4-oxo-4H-chromene-3 carbaldehyde. Then, by treating with different alpha-bromoalkylarylketones, we obtained N-substituted derivatives. All new compounds were investigated for their antimicrobial potential, using the diffusion method, against Listeria monocytogenes ATCC 13932, Staphylococcus aureus ATCC 49444, Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028 and Candida albicans ATCC 10231. Three concentrations, 10 mg/ml, 5 mg/ml and 1 mg/ml of compounds were used. The results were evaluated by the measurement of the inhibition zone diameters and compared to those of gentamicin and fluconazole respectively, as reference drugs. RESULTS: All new synthesized compounds were characterized using physico-chemical and spectrometric methods. They displayed modest to good antimicrobial activity. New molecules 8, 9 and 10 may represent promising candidates, showing zone inhibition diameters superior to those of reference drugs. CONCLUSIONS: This work presents chemical synthesis, characterization and investigation of the antibacterial and antifungal potential of 5-(chromene-3-yl)methylene-2,4-thiazolidinedione derivatives, which may be worthy of future research for designing new chemical entities. PMID- 27004036 TI - Development of a reservoir type prolonged release system with felodipine via simplex methodology. AB - BACKGROUND AND AIMS: Felodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method. METHODS: The first step of the Simplex method was to study the influence of the granules coating method on the felodipine release. Furthermore the influence of the coating polymer type, the percent of the coating polymer and the percent of pore forming agent in the coating on the felodipine release were studied. Afterwards these two steps of the experimental design the percent of Surelease applied on the felodipine loaded granules and the percent of pore former in the polymeric coating formulation variables were studied. The in vitro dissolution of model drug was performed in phosphate buffer solution (pH 6.5) with 1% sodium lauryl sulfate. The released drug quantification was done using an HPLC method. The release kinetics of felodipine from the final granules was assessed using different mathematical models. RESULTS: A 12 hours release was achieved using granules with the size between 315-500 MUm coated with 45% Surelease with different pore former ratios in the coating via the top-spray method. CONCLUSION: We have prepared prolonged release coated granules with felodipine using a fluid bed system based on the Simplex method. The API from the studied final formulations was released over a 12 hours period and the release kinetics of the model drug substance from the optimized preparations fitted best the Higuchi and Peppas kinetic models. PMID- 27004037 TI - Human tooth and root canal morphology reconstruction using magnetic resonance imaging. AB - BACKGROUND AND AIMS: Visualization of the internal and external root canal morphology is very important for a successful endodontic treatment; however, it seems to be difficult considering the small size of the tooth and the complexity of the root canal system. Film-based or digital conventional radiographic techniques as well as cone beam computed tomography provide limited information on the dental pulp anatomy or have harmful effects. A new non-invasive diagnosis tool is magnetic resonance imaging, due to its ability of imaging both hard and soft tissues. The aim of this study was to demonstrate magnetic resonance imaging to be a useful tool for imaging the anatomic conditions of the external and internal root canal morphology for endodontic purposes. METHODS: The endodontic system of one freshly extracted wisdom tooth, chosen for its well-known anatomical variations, was mechanically shaped using a hybrid technique. After its preparation, the tooth was immersed into a recipient with saline solution and magnetic resonance imaged immediately. A Bruker Biospec magnetic resonance imaging scanner operated at 7.04 Tesla and based on Avance III radio frequency technology was used. InVesalius software was employed for the 3D reconstruction of the tooth scanned volume. RESULTS: The current ex-vivo experiment shows the accurate 3D volume rendered reconstruction of the internal and external morphology of a human extracted and endodontically treated tooth using a dataset of images acquired by magnetic resonance imaging. The external lingual and vestibular views of the tooth as well as the occlusal view of the pulp chamber, the access cavity, the distal canal opening on the pulp chamber floor, the coronal third of the root canals, the degree of root separation and the apical fusion of the two mesial roots, details of the apical region, root canal curvatures, furcal region and interradicular root grooves could be clearly bordered. CONCLUSIONS: Magnetic resonance imaging offers 3D image datasets with more information than the conventional radiographic techniques. Due to its ability of imaging both hard and soft dental tissues, magnetic resonance imaging can be successfully used as a 3D diagnostic imaging technique in dentistry. When choosing the imaging method, dental clinicians should weight the benefit-risk ratio, taking into account the costs associated to magnetic resonance imaging and the harmful effects of ionizing radiations when cone beam computed tomography or conventional x-ray are used. PMID- 27004038 TI - Dental anxiety and fear among a young population with hearing impairment. AB - BACKGROUND AND AIM: Dental fear and anxiety is a major barrier for dental care provision. Identifying anxious patients can help dental professionals manage them appropriately. The study aimed at assessing dental fear and anxiety among a deaf population in Cluj-Napoca, Romania and their associated and contributing factors. METHOD: In this cross sectional study 165 deaf participants were invited to complete a questionnaire comprising three sections. The first section contained questions about social and economical status, the second comprised a Romanian version of the Modified Dental Anxiety Scale (MDAS) while part three was the Dental Fear Survey (DFS). Data was introduced and analyzed with the Statistical Package for Social Sciences (SPSS) program, version 20.0 (SPSS Inc., Chicago, Illinois, USA). RESULTS: Thirty four point nine percent (34.9%) of respondents were found to be insignificantly anxious, 59.7% were moderately or extremely anxious with 5.3% being identified with dental phobia based on the MDAS scores. Mean total score for dental anxiety on the MDAS scale was 13.7. Patients suffering from a prior negative experience were found to be more anxious (p<0.05). CONCLUSIONS: Dental fear and anxiety is widespread in the deaf communities. Higher percentages were observed among women and people with a previous traumatic dental experience. PMID- 27004039 TI - Role of nitro-oxidative stress in the pathogenesis of experimental rat periodontitis. AB - BACKGROUND AND AIMS: Periodontitis is a common chronic adult condition that implicates oxidative damage to gingival tissue, periodontal ligament and alveolar bone. This study aimed at assessing the association between the nitro-oxidative stress and the periodontal tissues destructions in experimental rat periodontitis. METHODS: Periodontitis was induced in 15 male albino rats by repetitive lesions to the gingiva adjacent to the inferior incisors, performed daily, for 16 days. On D1, D3, D6, D8, and D16 the onset and evolution of periodontitis were monitored by clinical and histopathological examinations; blood was collected and serum nitro-oxidative stress was evaluated through total nitrites and nitrates, total oxidative status, total antioxidant capacity, and oxidative stress index. RESULTS: The results demonstrated that there was a graded and continuous increase in serum levels of total nitrites and nitrates, total oxidative status and oxidative stress index, which was consistent with the severity of periodontal destructions during periodontitis progression. However, total antioxidant capacity was not significantly influenced by the disease progression. CONCLUSIONS: In experimental rat periodontitis, the systemic nitro oxidative stress was associated with the severity of periodontal destructions assessed clinically and histopathologically. Therefore, systemic nitro-oxidative stress parameters might be used as diagnostic tools in periodontitis. PMID- 27004040 TI - Clinico-pathologic, dermoscopic and ultrasound examination of a rare acral tumour involving the nail - case report and review of the literature. AB - There is a large spectrum of tumors presenting as nodular lesions that may affect the subungual space. We report the case of a 62-year-old woman presenting with a rapidly growing nodular lesion under the nail of the first left toe. Non-invasive examinations using dermoscopy, ultrasonography and elastography were performed for the preoperative assessment of the lesion. The biopsy of the lesion revealed superficial acral fibromyxoma, a benign tumor with predisposition for acral sites. The patient underwent radical surgery with wide resection margins. This is the first case report of a superficial acral fibromyxoma affecting the subungual region characterized by dermoscopic, ultrasonographic and elastographic features. We also performed a short review of the literature. PMID- 27004041 TI - Pannus-related prosthetic valve dysfunction. Case report. AB - Pannus-related prosthetic valve dysfunction, a complication of mechanical prosthetic valve replacement, is rare, with a slowly progressive evolution, but it can be acute, severe, requiring surgical reintervention. We present the case of a patient with a mechanical single disc aortic prosthesis, with moderate prosthesis-patient mismatch, minor pannus found on previous ultrasound examinations, who presented to our service with angina pain with a duration of 1 hour, subsequently interpreted as non-ST segment elevation myocardial infarction (NSTEMI) syndrome. Coronarography showed normal epicardial coronary arteries, an ample movement of the prosthetic disc, without evidence of coronary thromboembolism, and Gated Single-Photon Emission Computerized Tomography (SPECT) with Technetium (Tc)-99m detected no perfusion defects. Transthoracic echocardiography (TTE) evidenced a dysfunctional prosthesis due to a subvalvular mass; transesophageal echocardiography (TOE) showed the interference of this mass, with a pannus appearance, with the closure of the prosthetic disc. Under conditions of repeated angina episodes, under anticoagulant treatment, surgery was performed, with the intraoperative confirmation of pannus and its removal. Postoperative evolution was favorable. This case reflects the diagnostic and therapeutic management problems of pannus-related prosthetic valve dysfunction. PMID- 27004042 TI - Rene leriche and the development of 20(th) century surgery. AB - Rene Leriche (1879-1955) was a 20(th) century French surgeon generally known in medicine for the syndrome that carries his name, namely the Leriche syndrome in the aorto-iliac occlusive disease. This paper is published to mark the commemoration of 60 year since Leriche's death. Although Dr. Leriche's legacy resides in the domain of vascular medicine, his research enclosed bone pathology and surgical management of pain. Having his surgical training done under professors Mathieu Jaboulay and Antonin Poncet, his friendship and association with Alexis Carrel and William Halsted have contributed to Rene Leriche's development as a surgeon, researcher and thinker. Following the footsteps of his mentors, he produced outstanding clinical and academic work which had earned him a good reputation among his students and colleagues. Surgeons such as Jean Kunlin, Jao Cid dos Santos, Michael DeBakey, Rene Fontaine and others came to study and learn from him. These future generations of surgeons would themselves bring much contribution to the understanding and treatment of vascular diseases and medicine in general. Rene Leriche pioneered medicine with his research and ideas. His assiduous work of teaching, research and clinical practice made his influence last to our present. PMID- 27004043 TI - Characterization of intracellular palladium nanoparticles synthesized by Desulfovibrio desulfuricans and Bacillus benzeovorans. AB - Early studies have focused on the synthesis of palladium nanoparticles within the periplasmic layer or on the outer membrane of Desulfovibrio desulfuricans and on the S-layer protein of Bacillus sphaericus. However, it has remained unclear whether the synthesis of palladium nanoparticles also takes place in the bacterial cell cytoplasm. This study reports the use of high-resolution scanning transmission electron microscopy with a high-angle annular dark field detector and energy dispersive X-ray spectrometry attachment to investigate the intracellular synthesis of palladium nanoparticles (Pd NPs). We show the intracellular synthesis of Pd NPs within cells of two anaerobic strains of D. desulfuricans and an aerobic strain of B. benzeovorans using hydrogen and formate as electron donors. The Pd nanoparticles were small and largely monodispersed, between 0.2 and 8 nm, occasionally from 9 to 12 nm with occasional larger nanoparticles. With D. desulfuricans NCIMB 8307 (but not D. desulfuricans NCIMB 8326) and with B. benzeovorans NCIMB 12555, the NPs were larger when made at the expense of formate, co-localizing with phosphate in the latter, and were crystalline, but were amorphous when made with H2, with no phosphorus association. The intracellular Pd nanoparticles were mainly icosahedrons with surfaces comprising {111} facets and about 5 % distortion when compared with that of bulk palladium. The particles were more concentrated in the cell cytoplasm than the cell wall, outer membrane, or periplasm. We provide new evidence for synthesis of palladium nanoparticles within the cytoplasm of bacteria, which were confirmed to maintain cellular integrity during this synthesis. PMID- 27004044 TI - In their own words: a qualitative content analysis of women's and men's preferences for women's genitals. AB - Research increasingly shows genital attitudes have an impact on sexual well-being and health seeking behaviours. This study explored what women and men like and dislike about women's genitals. Data are from open-ended items, part of a cross sectional Internet-based survey anonymously completed by 496 women and 198 men. Overall, both women and men had positive attitudes towards women's genitals, although there was overlap between likes and dislikes. Some of the most common likes for women related to aesthetics and for men related to tactile and sexual aspects. Men listed more likes than dislikes. The emphasis on both positive and negative messages provides a more complete image of the complex ways people interact with their own and other's bodies and can help tailor clinical and educational messages. PMID- 27004045 TI - Case 2: Early Neonatal Seizures. PMID- 27004047 TI - Ethanolic extract of Commiphora mukul gum resin attenuates streptozotocin-induced alterations in carbohydrate and lipid metabolism in rats. AB - The purpose of this study was to investigate the effects of Commiphora mukul gum resin ethanolic extract (CMEEt) administration against altered activities of key enzymes of carbohydrate metabolism, lipid metabolism and changes in glycogen content (liver and muscle) and lipids (liver and heart) in streptozotocin (STZ) induced insulin deficient diabetic Wistar albino rats. Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg body wt) to male Wistar rats. The animals were divided into four groups: Control (C), control-treated (C+CM), diabetic (D) and diabetic-treated group (D+CM). Diabetic-treated and control treated rats were treated with C. mukul gum resin ethanolic extract (CMEEt) in 2 ml distilled water, orally (200 mg/kg body weight/day for 60 days). At the end of the experimental period, biochemical parameters related to carbohydrate and lipid metabolism were assayed. The significant enhancement in tissue lipids (heart and liver) total cholesterol, triglycerides, phospholipids and free fatty acids of diabetic rats were nearer to normalized in diabetic treated rats (D+CM). Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphofructokinase, pyruvate kinase, and glucose-6-phosphatase, fructose-1,6 bisphosphatase and glucose-6-phosphate dehydrogenase) and lipid metabolism (fatty acid synthase, malic enzyme and lipoprotein lipase) as observed in diabetic (D) rats were prevented with CMEEt administration. In conclusion, our findings indicate improvement of glucose and lipid metabolisms in STZ induced diabetic rats by treatment with Commiphora mukul and suggest that the plant can be used as an adjuvant for the prevention and/or management of insulin deficiency and disorder related to it. PMID- 27004046 TI - Citrate-Based Biomaterials and Their Applications in Regenerative Engineering. AB - Advances in biomaterials science and engineering are crucial to translating regenerative engineering, an emerging field that aims to recreate complex tissues, into clinical practice. In this regard, citrate-based biomaterials have become an important tool owing to their versatile material and biological characteristics including unique antioxidant, antimicrobial, adhesive, and fluorescent properties. This review discusses fundamental design considerations, strategies to incorporate unique functionality, and examples of how citrate-based biomaterials can be an enabling technology for regenerative engineering. PMID- 27004048 TI - Wound healing potential of Spirulina platensis extracts on human dermal fibroblast cells. AB - Blue-green alga (Spirulina platensis) is a well renowned nutri-supplement due to its high nutritional and medicinal properties. The aim of this study was to examine the wound healing efficiency of Spirulina platensis at various solvent extracts using in vitro scratch assay on human dermal fibroblast cells (HDF). Various gradient solvent extracts (50 MUg/ml of methanolic, ethanolic and aqueous extracts) from Spirulina platensis were treated on HDF cells to acquire its wound healing properties through scratch assay and in this investigation we have used allantoin, as a positive control to compare efficacy among the phytoextracts. Interestingly, aqueous extract were found to stimulate proliferation and migration of HDF cells at given concentrations and enhanced closure rate of wound area within 24 hours after treatment. Methanolic and ethanolic extracts have shown proliferative effect, however these extracts did not aid in the migration and closure of wound area when compared to aqueous extract. Based on phytochemical profile of the plant extracts analyzed by LC-MS/MS, it was shown that compounds supposedly involved in accelerating wound healing are cinnamic acid, narigenin, kaempferol, temsirolimus, phosphatidylserine isomeric derivatives and sulphoquinovosyl diacylglycerol. Our findings concluded that blue green algae may pose potential biomedical application to treat various chronic wounds especially in diabetes mellitus patients. PMID- 27004049 TI - Impact of socioeconomic and environmental factors on atopic eczema and allergic rhinitis: a cross sectional study. AB - The prevalence of allergic rhinitis and atopic eczema is on the rise in recent decades. Many factors can be related to the development of these diseases. We aimed to investigate the association between socioeconomic status (SES), environmental risk factors and these conditions. In this study, the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was translated and validated. Then it was used to determine the prevalence, severity and possible related factors for both diseases in 1904 schoolchildren aged 6-7 and 13 14 years from various regions of Tehran. The prevalence of rhinitis and eczema in the past year was 33.2 % and 8.2 %, respectively. The prevalence of rhinoconjunctivitis in the past year was 30 %. The risk factors such as birth order, nursery attendance, pet ownership, past allergic experiences as well as some SES factors were associated with both conditions. The prevalence of allergic rhinitis and atopic eczema was on the rise in comparison to the previous studies and SES as well as environmental factors are thought to be associated with the prevalence of these conditions. PMID- 27004050 TI - Study on genotoxicity, oxidative stress biomarkers and clinical symptoms in workers of an asbestos-cement factory. AB - The purpose of the present study was to investigate whether the markers of oxidative stress could be altered in workers exposed to asbestos. A comparative cross-sectional research was conducted in a group of 50 subjects exposed to asbestos and another group of 50 with the same age and sex unexposed to asbestos. Malondialdehyde (MDA), total thiol molecule (TTM), total antioxidant capacity (TAC), and DNA damage, were measured in the blood samples of workers and controls. Compared to the control group, the workers showed higher blood levels of DNA damage (P=0.0001) and MDA (P=0.0001). The workers showed lower TTM (P=0.02) as compared with the control group. There was no considerable difference on the level of TAC (P=0.1) between the groups. The workers indicated clinical symptoms such as breathlessness, phlegm, coughing and wheezing. There was a positive correlation between levels of 8-OHdG and MDA of asbestos workers and the smoking status suggesting the negative role of smoking. PMID- 27004051 TI - Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling. AB - Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, gamma-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2(Ser1254) decreased while ERK1/2 and TSC2(Thr1462) increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4E(Ser209) protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging. PMID- 27004052 TI - Patterns of changes and diagnostic values of FEF50%, FEF25%-75% and FEF50%/FEF25% 75% ratio in patients with varying control of bronchial asthma. AB - BACKGROUND: The pattern of change in FEF50%, FEF25%-75% and FEF50%/FEF25%-75% ratio depends on mechanics of forceful expiration, provided that non-homogenous lung emptying is faithfully recorded in the expiratory flow-volume loops. OBJECTIVE: To assess the potential clinical value of FEF50%, FEF25%-75% and FEF50%/FEF25%-75% ratio as an indicator of bronchial asthma (BA) control. METHODOLOGY: The study involved 75 patients with BA matched for age and gender with 45 non-asthmatic subjects. Based on asthma control test (ACT) and spirometry, asthmatic patients were subdivided into controlled and poorly controlled/uncontrolled. The relationship between FEF50% and FEF25%-75% as well as FEF50%/FEF25%-75% ratio and ACT score were assessed using linear regression. ROC curves were used to assess reliability of FEF25%-75% and FEF50% to diagnose BA in patients with different degree of asthma control. RESULTS: FEF50% correlated strongly with FEF25%-75% (r = 0.989, P < 0.001) and the relationship between the two indices is governed by the formula FEF50% = 1.132* FEF25%-75% - 0.003. There was no significant correlation (r = - 0.159, P = 0.083) between FEF50%/FEF25-75% ratio and ACT score. The diagnostic capability of FEF25%-75% for spirometric diagnosis of BA is only marginally better compared to FEF50% (area under ROC curves were 0.88 and 0.89 respectively, P < 0.001); however, diagnostic power of both spirometric indices deceased with poor BA control. CONCLUSION: FEF50%/FEF25%-75% has no clinical value as an indicator for BA control. Role of FEF25%-75% in evaluation of BA is marginally better than FEF50%; however, efficiency of both indices declined substantially as BA control worsened. PMID- 27004053 TI - Food intake, oral hygiene and gingival bleeding in pregnancy: does lifestyle make a difference? A cross sectional exploratory study. AB - OBJECTIVES: To investigate the association between lifestyle factors (food intake, sugary snacks consumption and oral health practices) and gingival bleeding during pregnancy. METHODS: A cross sectional exploratory study was conducted in the Maternity hospital, Dammam, Saudi Arabia. It included pregnant Saudi women selected using a convenience sample. Information was collected concerning participants' background, oral hygiene practices and visits to dentists. They were asked about the amount of food they consumed and their use of sugary snacks. Logistic regression analysis assessed the association between lifestyle factors and gingival bleeding. RESULTS: Responses were obtained from 197 women (92.1% response rate). Most women brushed their teeth but had < the recommended intake in the various food groups. Brushing was associated with lower odd of gingival bleeding (odds ratio= 0.47, 95% confidence interval= 0.23, 0.93) whereas intake of fewer servings than the recommended amounts in all food groups was associated with higher odds (odds ratio = 3.64, 95% confidence interval = 1.12, 11.82). CONCLUSION: Brushing and food intake during pregnancy are associated with gingival bleeding. Pregnant women can potentially improve their oral health by modifying their lifestyle and following healthier practices. PMID- 27004054 TI - Development of the Permanent Dentition and Validity of Demirjian and Goldstein Method for Dental Age Estimation in Sample of Saudi Arabian Children (Qassim Region). AB - OBJECTIVES: To determine dental maturity (dental age) in cross-sectional sample of Saudi Arabian children by applying the standards established by Demirjian and Golstein and to examine the applicability of these standards in determination of dental maturity among Saudi Arabian children (Qassim region). MATERIALS & METHODS: Dental maturity was assessed from panoramic radiographs of 400 Saudi Arabian children, 222 boys, and 198 girls ranging in age from 4 to 14 years by using these standards. The difference between the dental and chronological age in different age groups in both sexes was statistically compared using ANOVA testat 0.05 level of significance. RESULTS: The Saudi Arabian children were generally somewhat advanced in dental maturity compared with the French Canadian reference sample with an overall mean difference between the dental and chronological age of 0.279 years in boys and 0.385 years in girls. CONCLUSION: The applied standards appear to be adequate for studying dental age in groups of children among Saudi Arabian population. PMID- 27004055 TI - Cardiovascular disease risk profile among young Saudi women of Al-Qassim, Saudi Arabia: A cross-sectional study. AB - STUDY OBJECTIVE: The aim of the study was to assess the level of risk for cardiovascular diseases (CVD) among young Saudi women living in Al-Qassim, Saudi Arabia. METHODS: As part of "The Heart Protection Campaign" in the Al-Qassim region, data were collected from Saudi women using questionnaires as well as objective measurement of height, weight, blood pressure, and blood glucose. Data were analyzed using descriptive statistics. RESULTS: Only 15% of the sample were free of risk factors, the majority had either one (57.5%) or two (20.8%) risk factors. Additionally, 6.7% were considered to be at high-risk with three or more risk factors. The most common risk factors were physical inactivity (74%) and overweight/obesity, (25%/29%). There was a significant increase in the number of risk factors across age groups. Women over the age of 30 were more likely to have a higher number of risk factors than the younger women (20-24 years). CONCLUSIONS: Young women in Al-Qassim, Saudi Arabia have an unusually high risk for CVD. Since the number of risk factors increases substantially between the ages of 20 and 35, there is a need to develop prevention programs to lower the CVD risk through diet and exercise. PMID- 27004056 TI - Level of Physical Activity of Physicians Among Residency Training Program At Prince Sultan Military Medical City, Riyadh, KSA 2014. AB - INTRODUCTION: Physical exercise is a crucial component in maintaining a healthy life. Unfortunately, the prevalence of adequate physical activity among young physicians is low. Additionally, there was a few research estimating lifestyle habits and other preventive health measurements especially during their residency training program despite the importance of this topic. OBJECTIVES: The aim of this research is to determine the level of physical activity and the main barriers of being physically active among physicians at Prince Sultan Military Medical City (PSMMC). METHODS: An analytical cross-sectional study was adopted targeting the physicians of residency training program in different specialties at PSMMC, Riyadh, KSA. Data was collected using of short form of the International Physical Activity Questionnaire (IPAQ). RESULTS: The study showed that 68.4% of the participants had low level of physical activity (<=600-MET min/week). High physical activity level was more reported among male physicians compared to female physicians (4.3% versus 1.3%). The most frequent barriers of practicing physical activities among males were limited exercise facilities at home (71.7%), not suitable weather (69%) and the first priority is not for exercise (67.2%) whereas among females were no enough time to exercise (69.3%), lack of suitable places to exercise nearby (68%), the first priority is not for exercise (66.7%). CONCLUSION: Most of the physicians especially female residents reported low level of physical exercise due to many barriers. Overcoming these barriers may contribute to a further increase in the level of physical activity among them. PMID- 27004057 TI - Assessment of Mental Health among Iranian Medical Students: A Cross-Sectional Study. AB - OBJECTIVES: More mental morbidities were reported in medical students than their nonmedical peers, which may negatively influence their lives and future career. The aim of this study was to assess the mental health status among medical students of Shiraz University of Medical Sciences. METHOD: Two hundred and eight 1(st) to 4(th) year Medical students took part in this cross-sectional study. General Health Questionnaire with 28 items (GHQ-28) was used for data collection. We performed descriptive statistics, Mann Whitney U test, one way ANOVA and Tukey's post hoc and Kruskal Wallis H and Chi square test for statistical analysis. RESULTS: The mean age of participants was 20.70 +/- 1.14 (mean +/- SD) years. More than half of them (54.4%) had total GHQ score above the cut-off point considered as probably abnormal mental health status. Years of education, positive family history and low satisfaction of the medicine discipline affected their mental health. Third and fourth year students had significantly higher mean scores of total GHQ (p-value = 0.009) and anxiety, somatic and social subscales (p-value = 0.001, 0.004 and 0.026). Students with positive family history of mental illness and low satisfaction of field of the study significantly had higher GHQ scores (p-value = 0.012 and < 0.001 respectively). CONCLUSION: Poor mental health prevalence is high among medical students in Shiraz. Proper changes in educational programs and other effective interventions to raise the students' satisfaction may reduce the effect of other stress reasons and improve their mental health status. PMID- 27004058 TI - The Musculoskeletal Manifestations of Type 2 Diabetes Mellitus in a Kashmiri Population. AB - OBJECTIVES: Diabetes mellitus (DM), is affecting an ever increasing number of people worldwide. Diabetes is associated with several musculoskeletal manifestations. These may involve, the upper as well as the lower limb. We conducted this study to find out the prevalence of musculoskeletal problems in type 2 diabetics in the Kashmiri population. METHODOLOGY: The study was conducted on 403 patients with diabetes and 300 controls. All patients underwent screening for any musculoskeletal abnormalities. The patients with musculoskeletal abnormalities were further assessed to find the exact diagnosis according to predefined criteria. RESULTS: The hand was involved in 80 patients [19.8%] in the diabetic group and 15 (5%) patients of the control group. The elbow was affected in 56 patients [14%] in the diabetic group and 24 patients [5.9%] in the non diabetic group. The shoulder involvement was diagnosed in 61 patients [15%] on the diabetic cohort and 15 patients in the non-diabetic cohort. All the upper limb figures showed a statistically significant difference i.e. P value <0.05. CONCLUSION: The prevalence of musculoskeletal complications in type 2 diabetics in Kashmir is quite high. PMID- 27004059 TI - Anti-inflammatory activity of Euphorbia aegyptiaca extract in rats. AB - BACKGROUND: There were no studies on the anti-inflammatory activity of Euphorbia aegyptiaca, though it is commonly used by Sudanese herbalists in the treatment of rheumatoid arthritis. OBJECTIVES: To determine phytochemical constituents of Euphorbia aegyptiacaTo investigate the anti-inflammatory activity of Euphorbia aegyptiaca in rats. METHODOLOGY: Plant material was extracted by ethanol and phytochemical screening was done according to standard methods. The thickness of Albino rats' paws were measured before injection of 0.1 ml of 1% formalin in the sub planter region and then, 1, 2, 3, 4 and 24 hours after oral dose of ethanolic extract of Euphorbia aegyptiaca at a rate of 400mg/kg, 800mg/kg, indomethacin (5mg/kg) and normal saline (5ml/kg). Edema inhibition percentage (EI%) and mean paw thickness (MPT) were measured in the different groups and compared using appropriate statistical methods. RESULTS: The phytochemical screening revealed the presence of saponins, cumarins, flavonoids, tannins, sterols, triterpenes, and absence of alkaloids, anthraquinones glycosides and cyanogenic glycosides. The mean of EI% of rats treated with indomethacin at a dose of 5 mg/kg over different time intervals (64.0%) was significantly lower compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (75.0%, P< 0.001), but higher compared to rats treated at higher dose of 400 mg/kg (57.4%, P< 0.001). In contrast, MPT of rats treated with indomethacin at a dose of 5 mg/kg (6.5+/-1.1 mm) was significantly higher compared to those treated with Euphorbia aegyptiaca at a dose of 800 mg/kg (6.1+/-.7 mm, P< 0.001) as well as 400 mg/kg (5.9+/-.5, P< 0.001). CONCLUSION: Euphorbia aegyptiaca ethanolic extract has a sustained dose dependent anti-inflammatory activity. PMID- 27004060 TI - Awareness, utilization, and determinants of using oral diseases prevention methods among Saudi adults - a clinic-based pilot study. AB - OBJECTIVES: The present study was conducted to assess the level of awareness and utilization of methods to prevent oral diseases among a group of adult Saudis. METHODOLOGY: An anonymous, self-administered questionnaire was distributed to patients visiting the clinics of the College of Dentistry, University of Dammam in 2015. The questionnaire assessed the background of the respondents, their dental history, awareness and use of a number of methods available to prevent oral diseases, sources of information about these methods and barriers against their use. Regression analysis was used to assess the factors affecting the use of these practices. RESULTS: Brushing was reported to be used by about 60% of respondents whereas fluoride and sealant were less prevalent (<=30%). Dentist was the most frequently reported source of information about preventive methods (60%) and about 40% cited cost and time as the main reasons why they did not use these preventive methods. Awareness and age were associated with using a greater number of the various preventive methods (odds regression coefficient ratio= 0.27 and 0.04). CONCLUSIONS: Use of preventive methods is not prevalent among Saudi adults and it can be improved by more intensive efforts to increase the awareness of these methods, primarily through dentists. PMID- 27004061 TI - Teachers' knowledge about oral health and their interest in oral health education in Hail, Saudi Arabia. AB - OBJECTIVES: To assess the dental health knowledge and the interest of secondary school teachers in imparting oral health education in Hail, Saudi Arabia. METHODS: It was a questionnaire based cross-sectional survey of secondary school teachers in Hail, Saudi Arabia, carried out from November 2014 to January 2015. A validated self-administered questionnaire was used to determine teachers' oral health knowledge and their interest in participating in oral health education of school children. Data analysis was performed using SPSS version 20 statistical software. RESULTS: Two hundred and twenty three secondary school teachers responded to the survey. Results showed that about 80 to 90 % of teachers had sufficient knowledge of causes and prevention of dental caries and gingivitis. About 94% of teachers agreed that they can play an effective role in oral health promotion while 96% were found to be interested in performing additional duty as oral health promoter. A large majority (91.9 %) had the opinion that oral health education must be included in school curriculum. CONCLUSION: Teachers in Hail region had adequate amount of knowledge regarding oral health, and they were interested to play their role in promoting oral health education. Based on the findings of this study, it is recommended to include dental health education in curriculum at secondary school level and to provide sufficient training to teachers to enable them to participate actively in oral health promotion activities. PMID- 27004062 TI - Molecular Genetic of Atopic dermatitis: An Update. AB - Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date. PMID- 27004065 TI - Gigantobilharzia, possible cause of cercarial dermatitis: Case report. AB - Cercarial dermatitis (swimmer's itch) is a worldwide, often neglected parasitic skin disease characterized by strong maculopapular skin eruption accompanied by intensive itching. A fisherman suffered from forearm dermatitis. Clinical history associated with the recovery of the avian schistosome; Gigantobilharzia from little green bee-eater (Merops orientalis najdanus) and collected Lymnaea snails supported the authors' opinion that patient clinical signs are most likely due to the invasion of avian schistosome cercariae. PMID- 27004064 TI - Human papillomavirus related cervical cancer and anticipated vaccination challenges in Ethiopia. AB - Cervical cancer is the leading cause of cancer deaths among women in Ethiopia. This may be due to the high prevalence of high-risk human papillomavirus (HR-HPV) genotypes in the population. So far, few studies have been done that showed the presence of HR-HPV genotypes. The HR-HPV-16, -18, -52, -56, -31 and -58 were the most common genotypes reported in Ethiopia. The introduction of HPV vaccines in Ethiopia is likely to go a long way in reducing cervical cancer deaths. However, there are few challenges to the introduction of the vaccines. The target population for HPV vaccination is at the moment not well-defined. Besides, the current HPV vaccines confer only type-specific (HPV-16 and -18) immunity, leaving a small proportion of Ethiopian women unprotected against other HR-HPV genotypes such as 52, 56, 31 and 58. Thus, future HPV vaccines such as the nanovalent vaccine may be more useful to Ethiopia as they will protect women against more genotypes. PMID- 27004063 TI - An update of biochemical markers of hepatocellular carcinoma. AB - The definition of a tumor marker is broad, which covers a wide spectrum of biomacromolecules synthesized in excess concentration by a wide variety of neoplastic cells. Tumor markers can be normal endogenous products that are produced at a greater rate in cancer cells or the products of newly switched on genes that remained inactive in the normal cells. These markers consist of any products of either tumor itself or the host in reaction to tumor's presence that distinguishes malignant tissues from benign and is measurable in body fluids or tissues. They increase with progressive or recurrent disease, decrease with response to treatment, and normalize with remission. Clinical applications include screening in asymptomatic individuals, confirming a suspected diagnosis, assisting in tumor classification and staging, prognosis, monitoring treatment response, surveillance for residual disease, and early detection of recurrent disease. PMID- 27004066 TI - Prolonged Stress Leads to Serious Health Problems: Preventive Approaches. PMID- 27004067 TI - Unique Eomes(+) NK Cell Subsets Are Present in Uterus and Decidua During Early Pregnancy. AB - Decidual and uterine natural killer (NK) cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent "cytotoxic" group 1 innate lymphoid cells (ILCs) and are distinct from the recently described "helper" ILC1. Here, we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and decidua express Eomesodermin (Eomes), thus suggesting that they are developmentally related to conventional NK cells. However, they differ from peripheral NK cells. In humans, Eomes(+) decidual NK (dNK) cells express CD49a and other markers of tissue residency, including CD103, integrin beta7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNgamma-producing Eomes(+) NK cells. We show that TGFbeta can sustain/induce CD103 and CD9 expression in dNK cells and decidual CD34-derived NK cells, indicating that the decidual microenvironment can instruct the phenotype of Eomes(+) NK cells. In murine decidua and uterus, Eomes(+) cells include CD49a(-)CD49b(+) conventional NK cells and CD49a(+) cells. Notably, Eomes(+)CD49a(+) cells are absent in spleen and liver. Decidual and uterine Eomes(+)CD49a(+) cells can be dissected in two peculiar cell subsets according to CD49b expression. CD49a(+)CD49b ((-)) and CD49a(+)CD49b(+) cells are enriched in immature CD11b(low)CD27(high) cells, while CD49a(-)CD49b(+) cells contain higher percentages of mature CD11b(high)CD27(low) cells, both in uterus and decidua. Moreover, Eomes(+)CD49a(+)CD49b(-) cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes(-)CD49a(+) ILC1 population present in decidua and uterus increases during pregnancy. CD49b(-)Eomes(+/-) cells produce mainly TNF, while CD49a(-)CD49b(+) conventional NK cells and CD49a(+)CD49b(+) cells produce both IFNgamma and TNF. Thus, human and murine decidua contains unique subsets of group 1 ILCs, including Eomes(+) and Eomes(-) cells, with peculiar phenotypic and functional features. Our study contributes to re-examination of the complexity of uterine and decidual ILC subsets in humans and mice and highlights the role of the decidual microenvironment in shaping the features of these cells. PMID- 27004068 TI - alpha-Tocopheryl succinate-based amphiphilic block copolymers obtained by RAFT and their nanoparticles for the treatment of cancer. AB - alpha-Tocopheryl succinate (alpha-TOS) is a well-known mitochondrially targeted anticancer compound. However, the major factor limiting the use of alpha-TOS is its low solubility in physiological media. To overcome this problem, the aim of this work is the preparation of new polymeric and active alpha-TOS-based nanovehicle with a precise control over its macromolecular architecture. Reversible addition-fragmentation chain transfer polymerization (RAFT) is used to synthesize an alpha-TOS amphiphilic block copolymer with highly homogeneous molecular weight and relatively narrow dispersity. Macro-chain transfer agents (macro-CTA) based on poly(ethylene glycol) (PEG) of different molecular weights (MW, ranging from 4.6 to 20 kDa) are used to obtain block copolymers with different hydrophilic/hydrophobic ratios with PEG being the hydrophilic block and a methacrylic derivative of alpha-tocopheryl succinate (MTOS) being the monomer that formed the hydrophobic block. PEG-b-poly(MTOS) form spherical nanoparticles (NPs) by self-organized precipitation (SORP) or solvent exchange in aqueous media enabling to encapsulate and deliver hydrophobic molecules in their core. The resulting NPs are rapidly endocytosed by cancer cells. The biological activity of the synthesized NPs are found to depend on the MW of PEG, with NP comprised of the higher MW copolymer resulting in the lower bioactivity due to PEG shielding inhibiting cellular uptake by endocytosis. Moreover, the biological activity also depends on the MTOS content, as the biological activity increases as a function of MTOS concentration. PMID- 27004069 TI - Cancer Nanotechnology Startup Challenge: a new way to realize the fruits of innovation. AB - A significant new innovation-development model is being launched in the field of cancer and nanotechnology. A significant new innovation-development model is being launched in the field of cancer and nanotechnology. PMID- 27004070 TI - A Summary of a Cochrane Review: Yoga for epilepsy. PMID- 27004071 TI - Residents: admissions, training and assessment. PMID- 27004072 TI - Effects of a patient's name and image on medical knowledge acquisition. AB - PURPOSE: To assess whether there are differences in medical students' (MS) knowledge acquisition after being provided a virtual patient (VP) case summary with a patient's name and facial picture included compared to no patient's name or image. METHOD: 76 MS from four clerkship blocks participated. Blocks one and three (Treatment group) were provided case materials containing the patient's name and facial picture while blocks two and four (Control group) were provided similar materials without the patient's name or image. Knowledge acquisition was evaluated with a multiple-choice-question examination (CQA_K). RESULTS: Treatment group CQA_K scores were 64.6% (block one, n = 18) and 76.0% (block three, n = 22). Control group scores were 71.7%, (block two, n = 17) and 68.4% (block four, n = 19). ANOVA F-test among the four block mean scores was not significant; F (3, 72) = 1.68, p = 0.18, eta2=0.07. Only 22.2% and 27.3% of the MS from blocks one and three respectively correctly recalled the patient's name while 16.7% and 40.9% recalled the correct final diagnosis of the patient. CONCLUSIONS: These results suggest that including a patient's name and facial picture on reading materials may not improve MS knowledge acquisition. Corroborating studies should be performed before applying these results to the design of instructional materials. PMID- 27004073 TI - Preceptor engagement in distributed medical school campuses. AB - BACKGROUND: There is increasing interest in distributed medical campuses and engagement of physicians in these communities. To date, there has been suboptimal recruitment of physicians to participate in medical education at distributed campuses. The purpose of this project was to identify barriers to engagement in medical education by community physicians in the geographical catchment of the Waterloo Regional Campus of McMaster. METHOD: In-depth, semi-structured, qualitative interviews were conducted with physicians not involved in teaching. Interview recordings were transcribed and analyzed using a closed-loop, iterative coding methodology and thematic analysis was performed. Interviews were conducted until thematic saturation was achieved. RESULTS: Six interviews were conducted and coded. Nine key themes emerged: academic centre versus distributed sites, interest in teaching, financial considerations, administrative barriers, medical experience and knowledge currency, practice environment and schedule, training on teaching, setting up systems for learners in distributed campus settings, and student engagement and medical learner level. CONCLUSIONS: Barriers to engagement in teaching primarily focused on differences in job structure in the community, administrative barriers both at the hospital and through the medical school, and lack of knowledge on how to teach. As medical schools look to expand the capacity of distributed campuses, misperceptions should be addressed and opportunities to improve engagement should be further explored. PMID- 27004074 TI - Residents' perceptions of an integrated longitudinal curriculum: a qualitative study. AB - BACKGROUND: The purpose of this study was to explore family medicine residents' perceptions of a newly restructured integrated longitudinal curriculum. METHOD: A purposeful sample of 16 family medicine residents participated in focus group interviews conducted from a grounded theory perspective to identify the characteristics of this training model that contribute to and that challenge learning. RESULTS: Eight key themes were identified: continuity of care, relevance to family medicine, autonomy, program-focused preparation, professional development as facilitated by role modeling, patient volume, clarity of expectations for learners, and logistics. Positive learning experiences were marked by high levels of autonomy, continuity, and relevance to family medicine. Less favorable learning experiences were characterized by limited opportunities for continuity of care, limited relevance to family medicine practice and unclear expectations for the resident's role. Family physician-led learning experiences contributed to residents' understanding of the full scope of family medicine practice, more so than specialist-led experiences. The logistics of implementing the integrated block were challenging and negatively impacted continuity and learning. CONCLUSIONS: This study suggests that an integrated longitudinalized family medicine block training model has the potential to support the principles of a longitudinal integrated competency-based curriculum to effectively prepare residents for family medicine practice. PMID- 27004075 TI - Non-cognitive does not work; we need a new name. PMID- 27004076 TI - Pediatric faculty and residents' perspectives on In-Training Evaluation Reports (ITERs). AB - BACKGROUND: In-training evaluation reports (ITERs) are used by over 90% of postgraduate medical training programs in Canada for resident assessment. Our study examined the perspectives of faculty and residents in one pediatric program as a means to improve the ITER as an evaluation tool. METHOD: Two separate focus groups were conducted, one with eight pediatric residents and one with nine clinical faculty within the pediatrics program of Memorial University's Faculty of Medicine to discuss their perceptions of, and suggestions for improving, the use of ITERs. RESULTS: Residents and faculty shared many similar suggestions for improving the ITER as an evaluation tool. Both the faculty and residents emphasized the importance of written feedback, contextualizing the evaluation and timely follow-up. The biggest challenge appears to be the discrepancy in the quality of feedback sought by the residents and the faculty members' ability to do so in a time effective manner. Others concerns related to the need for better engagement in setting rotation objectives and more direct observation by the faculty member completing the ITER. CONCLUSIONS: The ITER is a useful tool in resident evaluations, but a number of issues relating to its actual use could improve the quality of feedback which residents receive. PMID- 27004077 TI - The importance of health advocacy in Canadian postgraduate medical education: current attitudes and issues. AB - BACKGROUND: Health advocacy is currently a key component of medical education in North America. In Canada, Health Advocate is one of the seven roles included in the Royal College of Physicians and Surgeons of Canada's CanMEDS competency framework. METHOD: A literature search was undertaken to determine the current state of health advocacy in Canadian postgraduate medical education and to identify issues facing educators and learners with regards to health advocacy training. RESULTS: The literature revealed that the Health Advocate role is considered among the least relevant to clinical practice by educators and learners and among the most challenging to teach and assess. Furthermore learners feel their educational needs are not being met in this area. A number of key barriers affecting health advocacy education were identified including limited published material on the subject, lack of clarity within the role, insufficient explicit role modeling in practice, and lack of a gold standard for assessment. Health advocacy is defined and its importance to medical practice is highlighted, using pediatric emergency medicine as an example. CONCLUSIONS: Increased published literature and awareness of the role, along with integration of the new 2015 CanMEDS framework, are important going forward to address concerns regarding the quality of postgraduate health advocacy education in Canada. PMID- 27004078 TI - Comparing the traditional and Multiple Mini Interviews in the selection of post graduate medical trainees. AB - BACKGROUND: The traditional, panel style interview and the multiple mini interview (MMI) are two options to use in the selection of medical trainees with each interview format having inherent advantages and disadvantages. Our aim was to compare the traditional and MMI on the same cohort of postgraduate applicants to the Department of Otolaryngology - Head & Neck Surgery at the University of Toronto. METHOD: Twenty-seven applicants from the 2010 Canadian Residency Matching Service selected for interview at the University of Toronto, Department of Otolaryngology - Head & Neck Surgery were included in the study. Each applicant participated in both a traditional interview and MMI. RESULTS: Traditional interviews marked out of a total maximum score of 570. On the traditional interview, scores ranged from 397-543.5 (69.6 - 95.3%), the mean was 460.2. The MMI maximum score was out of 180. MMI scores ranged from 93 - 146 (51.7 - 81.1%) with a mean of 114.8. Traditional interview total scores were plotted against MMI total scores. Scores correlated reasonably well, Pearson Correlation = 0.315 and is statistically significant at p = 0.001. Inter interview reliability for the two interview methods was 0.038, with poor overall agreement 0.07%. CONCLUSIONS: MMI and traditional interview scores are correlated but do not reliably lead to the same rank order. We have demonstrated that these two interview formats measure different characteristics. One format may also be less reliable leading to greater variation in final rank. Further validation research is certainly required. PMID- 27004079 TI - Using script theory to cultivate illness script formation and clinical reasoning in health professions education. AB - Script theory proposes an explanation for how information is stored in and retrieved from the human mind to influence individuals' interpretation of events in the world. Applied to medicine, script theory focuses on knowledge organization as the foundation of clinical reasoning during patient encounters. According to script theory, medical knowledge is bundled into networks called 'illness scripts' that allow physicians to integrate new incoming information with existing knowledge, recognize patterns and irregularities in symptom complexes, identify similarities and differences between disease states, and make predictions about how diseases are likely to unfold. These knowledge networks become updated and refined through experience and learning. The implications of script theory on medical education are profound. Since clinician-teachers cannot simply transfer their customized collections of illness scripts into the minds of learners, they must create opportunities to help learners develop and fine-tune their own sets of scripts. In this essay, we provide a basic sketch of script theory, outline the role that illness scripts play in guiding reasoning during clinical encounters, and propose strategies for aligning teaching practices in the classroom and the clinical setting with the basic principles of script theory. PMID- 27004081 TI - Education of doctors providing service to LGBTQ patients. PMID- 27004080 TI - Internal Medicine residents use heuristics to estimate disease probability. AB - BACKGROUND: Training in Bayesian reasoning may have limited impact on accuracy of probability estimates. In this study, our goal was to explore whether residents previously exposed to Bayesian reasoning use heuristics rather than Bayesian reasoning to estimate disease probabilities. We predicted that if residents use heuristics then post-test probability estimates would be increased by non discriminating clinical features or a high anchor for a target condition. METHOD: We randomized 55 Internal Medicine residents to different versions of four clinical vignettes and asked them to estimate probabilities of target conditions. We manipulated the clinical data for each vignette to be consistent with either 1) using a representative heuristic, by adding non-discriminating prototypical clinical features of the target condition, or 2) using anchoring with adjustment heuristic, by providing a high or low anchor for the target condition. RESULTS: When presented with additional non-discriminating data the odds of diagnosing the target condition were increased (odds ratio (OR) 2.83, 95% confidence interval [1.30, 6.15], p = 0.009). Similarly, the odds of diagnosing the target condition were increased when a high anchor preceded the vignette (OR 2.04, [1.09, 3.81], p = 0.025). CONCLUSIONS: Our findings suggest that despite previous exposure to the use of Bayesian reasoning, residents use heuristics, such as the representative heuristic and anchoring with adjustment, to estimate probabilities. Potential reasons for attribute substitution include the relative cognitive ease of heuristics vs. Bayesian reasoning or perhaps residents in their clinical practice use gist traces rather than precise probability estimates when diagnosing. PMID- 27004082 TI - Response to: Education of doctors providing service to LGBTQ patients. PMID- 27004083 TI - Fast and Standardized Skin Grafting of Leg Wounds With a New Technique: Report of 2 Cases and Review of Previous Methods. AB - BACKGROUND: Chronic leg ulcers remain a challenge to the treating physician. Such wounds often need skin grafts to heal. This necessitates a readily available, fast, simple, and standardized procedure for grafting. OBJECTIVES: The aim of this work was to test a novel method developed for outpatient transplant procedures. METHODS: The procedure employs a handheld disposable dermatome and a roller mincer that cut the skin into standardized micrografts that can be spread out onto a suitable graft bed. Wounds were followed until healed and photographed. RESULTS: The device was successfully used to treat and close a traumatic lower limb wound and a persistent chronic venous leg ulcer. The donor site itself healed by secondary intent with minimal cosmetic impairment. CONCLUSION: The method was successfully used to graft 2 lower extremity wounds. PMID- 27004084 TI - Erratum to: The standard operating procedure of the DOE-JGI Microbial Genome Annotation Pipeline (MGAP v.4). AB - [This corrects the article DOI: 10.1186/s40793-015-0077-y.]. PMID- 27004085 TI - Providing Guidance for Patients With Moderate-to-Severe Psoriasis Who Are Candidates for Biologic Therapy: Role of the Nurse Practitioner and Physician Assistant. AB - Psoriasis is a chronic, immune-mediated disease characterized by itchy, scaly, and often painful plaques in the skin. Psoriasis can have significant psychosocial burdens and increased risks for numerous comorbidities, including diabetes, hypertension, and cardiovascular disease, particularly in patients with moderate-to-severe disease. Dermatology nurse practitioners and physician assistants are an important part of the healthcare team, contributing to all aspects of psoriasis management. This review reinforces the unique aspects of care that nurse practitioners and physician assistants provide to patients with psoriasis, such as facilitating conversations about managing disease, setting appropriate expectations, and considering treatment options, including when treatment response or tolerability is suboptimal. The importance of relationship building is stressed. Patient management topics discussed include helpful tips about assessing treatment options, initiating biologic therapy, optimizing patient adherence, and managing comorbidities. Also reviewed are how to deal with common barriers including lack of knowledge about psoriasis or making healthy lifestyle changes, fear of injections or side effect risks, lack of health insurance, and concerns about treatment costs. Overall, by forming meaningful relationships and engaging patients in their psoriasis care, nurse practitioners and physician assistants can help to optimize clinical efficacy outcomes and consistently manage moderate-to-severe psoriasis and its comorbidities over the patient's life course. PMID- 27004086 TI - Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations. AB - The proportion of hepatitis B virus (HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation (HBVr) increases with the presence of hepatitis B surface antigen (HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines. PMID- 27004087 TI - Management of human factors engineering-associated hemochromatosis: A 2015 update. AB - This review focuses on the management of iron metabolism and iron overload experienced in the hereditary condition, human factors engineering (HFE) associated hemochromatosis. Hemochromatosis refers to a group of genetic diseases that result in iron overload; the major one globally is HFE-associated hemochromatosis. The evolution in understanding of the most common form of hereditary hemochromatosis, being the substation of cysteine to a tyrosine at position 282 in the HFE gene, has been extensively studied Novel mutations in both HFE and non-HFE genes have been indicated in this disease which hold significance in its application for the Asia-Pacific region. In conditions with iron overload, the storage of excess iron in various body tissues leads to complications and toxic damage. The most common presenting complaint for this disease is malaise, lethargy and other non-specific symptoms. In order to diagnose hereditary hemochromatosis, there are biochemical, imaging and genetic testing options. Currently, cascade screening of affected families is preferred over population-level screening. The mainstay of treatment is venesection and the appropriate approach to treatment has been consolidated over the years. Recently, the indications for venesection therapy of hemochromatosis have been challenged and are the subject of ongoing research. PMID- 27004088 TI - Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4(-/-) mouse model. AB - AIM: To study the interleukin-1 (IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4(-/-) (Abcb4(-/-)) mouse model. METHODS: Female and male Abcb4(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis (liver serum tests), extent of liver fibrosis (hydroxyproline content and Sirius red staining) and tissue specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction (qPCR)]. For in vivo experiments, murine hepatic stellate cells (HSCs) were isolated via pronase-collagenase perfusion followed by density gradient centrifugation using female mice. Murine HSCs were stimulated with up to 1 ng/mL IL-1beta with or without 2.5 MUg/mL Anakinra, an IL-1 receptor antagonist, respectively. The proliferation of murine HSCs was assessed via the BrdU assay. The toxicity of Anakinra was evaluated via the fluorescein diacetate hydrolysis (FDH) assay. In vivo 8-wk-old Abcb4(-/-) mice with an already fully established hepatic phenotype were treated with Anakinra (1 mg/kg body-weight daily intraperitoneally) or vehicle and liver injury and liver fibrosis were evaluated via serum tests, qPCR, hydroxyproline content and Sirius red staining. RESULTS: Liver fibrosis was less pronounced in males than in female Abcb4(-/-) animals as defined by a lower hydroxyproline content (274 +/- 64 MUg/g vs 436 +/- 80 MUg/g liver, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test) and lower mRNA expression of the profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP) (1 +/- 0.41 vs 0.66 +/- 0.33 fold, respectively; n = 13-15; P < 0.05; Mann-Whitney U-test). Reduced liver fibrosis was associated with significantly lower levels of F4/80 mRNA expression (1 +/- 0.28 vs 0.71 +/- 0.41 fold, respectively; n = 12-15; P < 0.05; Mann-Whitney U-test) and significantly lower IL-1beta mRNA expression levels (1 +/- 0.38 vs 0.44 +/- 0.26 fold, respectively; n = 13-15; P < 0.001; Mann-Whitney U-test). No gender differences in the serum liver parameters [bilirubin; alanine aminotransferase (ALT); aspartate aminotransferase and alkaline phosphatase (AP)] were found. In vitro, the administration of IL-1beta resulted in a significant increase in HSC proliferation [0.94 +/- 0.72 arbitrary units (A.U.) in untreated controls, 1.12 +/- 0.80 A.U. at an IL-1beta concentration of 0.1 ng/mL and 1.18 +/- 0.73 A.U. at an IL-1beta concentration of 1 ng/mL in samples from n = 6 donor animals; P < 0.001; analyses of variance (ANOVA)]. Proliferation was reduced significantly by the addition of 2.5 MUg/mL Anakinra (0.81 +/- 0.60 A.U. in untreated controls, 0.92 +/- 0.68 A.U. at an IL-1beta concentration of 0.1 ng/mL, and 0.91 +/- 0.69 A.U. at an IL-1beta concentration of 1 ng/mL; in samples from n = 6 donor animals; P < 0.001; ANOVA) suggesting an anti-proliferative effect of this clinically approved IL-1 receptor antagonist. The FDH assay showed this dose to be non-toxic in HSCs. In vivo, Anakinra had no effect on the hepatic hydroxyproline content, liver serum tests (ALT and AP) and pro-fibrotic (collagen 1alpha1, collagen 1alpha2, transforming growth factor-beta, and TIMP-1) and anti fibrotic [matrix metalloproteinase 2 (MMP2), MMP9 and MMP13] gene expression after 4 wk of treatment. Furthermore, the hepatic IL-1beta and F4/80 mRNA expression levels were unaffected by Anakinra treatment. CONCLUSION: IL-1beta expression is associated with the degree of liver fibrosis in Abcb4(-/-) mice and promotes HSC proliferation. IL-1 antagonism shows antifibrotic effects in vitro but not in Abcb4(-/-) mice. PMID- 27004089 TI - Retrocaval liver lifting maneuver and modifications of total hepatic vascular exclusion for liver tumor resection. AB - AIM: To evaluate the efficacy of technical modifications of total hepatic vascular exclusion (THVE) for hepatectomy involving inferior vena cava (IVC). METHODS: Of 301 patients who underwent hepatectomy during the immediate previous 5-year period, 8 (2.7%) required THVE or modified methods of IVC cross-clamping for resection of liver tumors with massive involvement of the IVC. Seven of the patients had diagnosis of colorectal liver metastases and 1 had diagnosis of hepatocellular carcinoma. All tumors involved the IVC, and THVE was unavoidable for combined resection of the IVC in all 8 of the patients. Technical modifications of THVE were applied to minimize the extent and duration of vascular occlusion, thereby reducing the risk of damage. RESULTS: Broad dissection of the space behind the IVC coupled with lifting up of the liver from the retrocaval space was effective for controlling bleeding around the IVC before and during THVE. The procedures facilitate modification of the positioning of the cranial IVC cross-clamp. Switching the cranial IVC cross-clamp from supra- to retrohepatic IVC or to the confluence of hepatic vein decreased duration of the THVE while restoring hepatic blood flow or systemic circulation via the IVC. Oblique cranial IVC cross-clamping avoided ischemia of the remnant hemi-liver. With these technical modifications, the mean duration of THVE was 13.4 +/- 8.4 min, which was extremely shorter than that previously reported in the literature. Recovery of liver function was smooth and uneventful for all 8 patients. There was no case of mortality, re-operation, or severe complication (i.e., Clavien Dindo grade of III or more). CONCLUSION: The retrocaval liver lifting maneuver and modifications of cranial cross-clamping were useful for minimizing duration of THVE. PMID- 27004090 TI - Nuclear stress perfusion imaging versus computed tomography coronary angiography for identifying patients with obstructive coronary artery disease as defined by conventional angiography: insights from the CorE-64 multicenter study. AB - We investigated the diagnostic accuracy of computed tomography angiography (CTA) versus myocardial perfusion imaging (MPI) for detecting obstructive coronary artery disease (CAD) as defined by conventional quantitative coronary angiography (QCA). Sixty-three patients who were enrolled in the CorE-64 multicenter study underwent CTA, MPI, and QCA imaging. All subjects were referred for cardiac catheterization with suspected or known coronary artery disease. The diagnostic accuracy of quantitative CTA and MPI for identifying patients with 50% or greater coronary arterial stenosis by QCA was evaluated using receiver operating characteristic (ROC) analysis. Pre-defined subgroups were patients with known CAD and those with a calcium score of 400 or over. Diagnostic accuracy by ROC analysis revealed greater area under the curve (AUC) for CTA than MPI for all 63 patients: 0.95 [95% confidence interval (CI): 0.89-0.100] vs 0.65 (95%CI: 0.53 0.77), respectively (P<0.01). Sensitivity, specificity, positive and negative predictive values were 0.93, 0.95, 0.97, 0.88, respectively, for CTA and 0.85, 0.45, 0.74, 0.63, respectively, for MPI. In 48 patients without known CAD, AUC was 0.96 for CTA and to 0.67 for SPECT (P<0.01). There was no significant difference in AUC for CTA in patients with calcium score below 400 versus over 400 (0.93 vs 0.95), but AUC was different for SPECT (0.61 vs 0.95; P<0.01). In a direct comparison, CTA is markedly superior to MPI for detecting obstructive coronary artery disease in patients. Even in subgroups traditionally more challenging for CTA, SPECT does not offer similarly good diagnostic accuracy. CTA may be considered the non-invasive test of choice if diagnosis of obstructive CAD is the purpose of imaging. PMID- 27004091 TI - Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol) on parasympathetic and sympathetic activity: a comparison of measures. AB - BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is recognized as a significant health risk. Specific and sensitive measures of CAN are needed for early identification and treatment to avoid complications, preferably in the preclinical state. OBJECTIVES: In this first of two articles, the patient cohort is described and two measures of autonomic function are reviewed: the traditional heart rate variability (HRV)-alone method and the newer parasympathetic and sympathetic (P&S) Method. These systems are then evaluated against known effects of the alpha/beta-adrenergic blocker, Carvedilol, and the selective beta adrenergic blocker, Metoprolol, on P&S activity. METHODS: Serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1) introduced, (2) discontinued or (3) continued without adjustment. Group 3 served as the control. HRV-alone parameters are computed according to standards. The P&S Method, which is a time-frequency analyses of concurrent respiratory activity and HRV, is elucidated, as developed at MIT and Harvard Medical School (1981). RESULTS: The HRV-alone demonstrated that introducing either medication increased low frequency (msec(2)) and standard deviation of the beat-to-beat (N-N) interval (msec), as expected. The other HRV parameter responses were not consistent with expectations. Similar inconsistencies occurred when either medication was discontinued. The P&S Method demonstrated that introducing or discontinuing either agent decreased or increased sympathetic activity, respectively, according to expectations. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol. CONCLUSION: Autonomic assessment fidelity was significantly higher with the P&S Method as validated by comparison with previously known physiology of the cardiovascular system. PMID- 27004092 TI - Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol) on parasympathetic and sympathetic activity: a comparison of clinical results. AB - BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is recognized as a significant health risk, correlating with risk of heart disease, silent myocardial ischemia or sudden cardiac death. Beta-blockers are often prescribed to minimize risk. OBJECTIVES: In this second of two articles, the effects on parasympathetic and sympathetic activity of the alpha/beta-adrenergic blocker, Carvedilol, are compared with those of the selective beta-adrenergic blocker, Metoprolol. METHODS: Retrospective, serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1) introduced, (2) discontinued or (3) continued without adjustment. Group 3 served as the control. RESULTS: Introducing Carvedilol or Metoprolol decreased heart rate and blood pressure, and discontinuing them had the opposite effect. Parasympathetic activity increased with introducing Carvedilol. Sympathetic activity increased more after discontinuing Carvedilol, suggesting better sympathetic suppression. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol. CONCLUSION: Carvedilol has a more profound effect on sympathovagal balance than Metoprolol. While both suppress sympathetic activity, only Carvedilol increases parasympathetic activity. Increased parasympathetic activity may underlie the lower mortality risk with Carvedilol. PMID- 27004093 TI - Intravenous sildenafil in right ventricular dysfunction with pulmonary hypertension following a heart transplant. AB - The objective of the present work is to describe the experience with intravenous (IV) sildenafil in heart transplant (HT) patients with reactive pulmonary hypertension (PH) who developed right ventricular dysfunction (RVD) in the immediate postoperative period. The first 5 patients who received IV sildenafil followinga HT are presented. The HTs took place between March 2011 and September 2012 in patients aged 37 to 64 years; all patients were male. Prior to the HT, mean pulmonary artery pressure (mPAP) was 32-56 mmHg. In all cases, the hemodynamic study demonstrated PH reactivity (positive vasodilator test with nitric oxide). All 5 patients developed RVD with hemodynamic instability immediately after the HT, despite the administration of nitric oxide from the time of intubation prior to the implant, optimal medical treatment in all cases, and a ventricular assist in 2 cases. In all patients, IV sildenafil was initiated at 10 mg/8 h for 48 h and was subsequently increased to 20 mg/8 h. in its oral formulation until discharge from the hospital. The change in pulmonary pressure was assessed using a Swan-Ganz catheter. Ventricular function was assessed using echocardiography. Length of stay in the Resuscitation Unit and mid-term survival were also assessed. Average time of extracorporeal circulation was 200 +/- 110 min and organ ischemic time was 210 +/- 95 min. All of the patients demonstrated pulmonary and systemic hemodynamic improvement, as well as recovery of right ventricular function after completing the treatment with IV sildenafil. The stay in the Resuscitation Unit lasted 3-25 days. All the patients were discharged from hospital with no mortality to date. Intravenous sildenafil improves right ventricle hemodynamics associated with pulmonary hypertension post-HT. Prophylactic prevention with this drug could be indicated for patients with reactive PH who are about to receive a transplant. PMID- 27004094 TI - The double helix angiography of right coronary arteries: false lumen stenting of a type F right coronary artery spiral dissection with late recanalization of the true lumen and occlusion of the stented false lumen. AB - Guide catheter induced dissection of coronary arteries is an uncommon, but serious complication of coronary angioplasty. Treatment can include emergent coronary artery bypass grafting to the affected vessel or percutaneous intervention including wiring the true lumen and exclusion stenting of the dissection flap to prevent further propagation. Detailed descriptions have been published of techniques of intentional passage of guide wires into the false lumen and reentry into the true lumen with chronic total occlusions. We present an unusual case of what appeared to be successful intentional false lumen stenting with reentry into the true lumen of an iatrogenic dissection of the right coronary artery with restoration of TIMI III coronary flow which, one year later, was complicated by recanalization of the true lumen and occlusion of the stented false lumen causing symptomatic angina. PMID- 27004095 TI - An unusual cause of ventricular tachycardia: Port-A-Cath fracture and embolization into the pulmonary artery. AB - We describe the case of a patient with a previously placed Port-A-Cath who was admitted to hospital for new onset of non-flushing catheter and palpitations with ventricular tachycardia. A chest X-ray and a linogram showed a Port-A-Cath fracture and distal embolization into the right ventricle resulting in ventricular tachycardia. The catheter was removed percutaneously using a Goose Neck snare with no complications and resolution of the ventricular tachycardia. The removed segment demonstrated thrombus. Prompt removal of the embolized catheter fragments should be undertaken given the subtle nature of the embolization and the potential complications. PMID- 27004096 TI - Marked prolongation of QRS duration after initiation of dronedarone therapy. AB - Dronedarone is a relatively new antiarrhythmic drug and is held to be less proarrhythmic than comparable compounds, although its proarrhythmia potential in humans has not been sufficiently evaluated. We describe a so far unreported dronedarone effect, namely a significant alteration of both the morphology and the duration of the QRS complex on the electro cardiogram in a 41-year old patient with symptomatic paroxysmal atrial fibrillation. PMID- 27004097 TI - Cardiac autonomic testing and diagnosing heart disease. "A clinical perspective". AB - BACKGROUND: Coronary heart disease (CHD) is a major health concern, affecting nearly half the middle-age population and responsible for nearly one-third of all deaths. Clinicians have responsibilities beyond diagnosing CHD, including risk stratification of patients for major adverse cardiac events (MACE), modifying the risks and treating the patient. In this first of a two-part review, identifying risk factors is reviewed, including more potential benefit from autonomic testing. METHODS: Traditional and non-traditional, and modifiable and non modifiable risk factors for MACE where compared, including newer risk factors, such as inflammation, carotid intimal thickening, ankle-brachial index, CT calcium scoring, and autonomic function testing, specifically independent measurement of parasympathetic and sympathetic (P&S) activity. RESULTS: The Framingham Heart Study, and others, have identified traditional risk factors for the development of CHD. These factors effectively target high-risk patients, but a large number of individuals who will develop CHD and MACE are not identified. Many patients with CHD who appear to be well-managed by traditional therapies still experience MACE. In order to identify these patients, other possible risk factors have been explored. Advanced autonomic dysfunction, and its more severe form, cardiac autonomic neuropathy, have been strongly associated with an elevated risk of cardiac mortality and are diagnosable through P&S testing. CONCLUSIONS: Independent measures of P&S activity, provides additional information and has the potential to incrementally add to risk assessment. This additional information enables physicians to (1) specifically target more high risk patients and (2) titrate therapies, with autonomic testing guidance, in order to minimize risk of cardiac mortality and morbidity. PMID- 27004098 TI - Cardiac autonomic testing and treating heart disease. "A clinical perspective". AB - BACKGROUND: Coronary heart disease (CHD) is a major health concern, affecting nearly half the middle-age population and responsible for nearly one-third of all deaths. Clinicians have several major responsibilities beyond diagnosing CHD, such as risk stratification of patients for major adverse cardiac events (MACE) and treating risks, as well as the patient. This second of a two-part review series discusses treating risk factors, including autonomic dysfunction, and expected outcomes. METHODS: Therapies for treating cardiac mortality risks including cardiovascular autonomic neuropathy (CAN), are discussed. RESULTS: While risk factors effectively target high-risk patients, a large number of individuals who will develop complications from heart disease are not identified by current scoring systems. Many patients with heart conditions, who appear to be well-managed by traditional therapies, experience MACE. Parasympathetic and Sympathetic (P&S) function testing provides more information and has the potential to further aid doctors in individualizing and titrating therapy to minimize risk. Advanced autonomic dysfunction (AAD) and its more severe form cardiovascular autonomic neuropathy have been strongly associated with an elevated risk of cardiac mortality and are diagnosable through autonomic testing. This additional information includes patient-specific physiologic measures, such as sympathovagal balance (SB). Studies have shown that establishing and maintaining proper SB minimizes morbidity and mortality risk. CONCLUSIONS: P&S testing promotes primary prevention, treating subclinical disease states, as well as secondary prevention, thereby improving patient outcomes through (1) maintaining wellness, (2) preventing symptoms and disorder and (3) treating subclinical manifestations (autonomic dysfunction), as well as (4) disease and symptoms (autonomic neuropathy). PMID- 27004099 TI - Heart valve surgery: EuroSCORE vs. EuroSCORE II vs. Society of Thoracic Surgeons score. AB - BACKGROUND: This is a validation study comparing the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II with the previous additive (AES) and logistic EuroSCORE (LES) and the Society of Thoracic Surgeons' (STS) risk prediction algorithm, for patients undergoing valve replacement with or without bypass in Pakistan. PATIENTS AND METHODS: Clinical data of 576 patients undergoing valve replacement surgery between 2006 and 2013 were retrospectively collected and individual expected risks of death were calculated by all four risk prediction algorithms. Performance of these risk algorithms was evaluated in terms of discrimination and calibration. RESULTS: There were 28 deaths (4.8%) among 576 patients, which was lower than the predicted mortality of 5.16%, 6.96% and 4.94% by AES, LES and EuroSCORE II but was higher than 2.13% predicted by STS scoring system. For single and double valve replacement procedures, EuroSCORE II was the best predictor of mortality with highest Hosmer and Lemmeshow test (H-L) p value (0.346 to 0.689) and area under the receiver operating characteristic (ROC) curve (0.637 to 0.898). For valve plus concomitant coronary artery bypass grafting (CABG) patients actual mortality was 1.88%. STS calculator came out to be the best predictor of mortality for this subgroup with H-L p value (0.480 to 0.884) and ROC (0.657 to 0.775). CONCLUSIONS: For Pakistani population EuroSCORE II is an accurate predictor for individual operative risk in patients undergoing isolated valve surgery, whereas STS performs better in the valve plus CABG group. PMID- 27004100 TI - Ranolazine improves autonomic balance in heart failure when added to guideline driven therapy. AB - BACKGROUND: The effect of ranolazine (RAN) on cardiac autonomic balance in congestive heart failure (CHF) was studied. METHODS: Fifty-four CHF patients were randomized to (1) open-label RAN (RANCHF) added to usual therapy vs. (2) usual therapy (NORANCHF). Parasympathetic and sympathetic (P&S) measurements were taken at baseline and at 12 months. RESULTS: A total of 16/27 (59%) patients in both groups had initially abnormal P&S measures, including high sympathovagal balance (SB), cardiovascular autonomic neuropathy (CAN) or both. High SB normalized in 10/12 (83%) RANCHF patients vs. 2/11 (18%) NORANCHF patients. SB became high in 5/11 (45%) NORANCHF vs. 1/11 (9%) RANCHF patients. CAN improved in 4/6 (67%) RANCHF patients vs. 5/7 (45%) NORANCHF patients. CAN developed in 1/11 (9%) RANCHF vs. 4/11 (36%) NORANCHF patients. Since improved P&S in RANCHF patients seemed independent of improved brain natriuretic peptide and impedance cardiography (BioZ) measurements, 5 day RAN was given to 30 subjects without CHF but with high SB or CAN. P&S improved in 90% of these subjects. CONCLUSIONS: RAN improves unfavorable P&S activity in CHF possibly by a direct effect upon autonomic sodium channels. PMID- 27004101 TI - Ranolazine preserves and improves left ventricular ejection fraction and autonomic measures when added to guideline-driven therapy in chronic heart failure. AB - BACKGROUND: Ranolazine (RAN) reduces cardiac sodium channel 1.5's late sodium current in congestive heart failure (CHF), reducing myocardial calcium overload, potentially improving left ventricular (LV) function. RAN blocks neuronal sodium channel 1.7, potentially altering parasympathetic and sympathetic (P&S) activity. The effects of RAN on LV ejection fraction (LVEF) and P&S function in CHF were studied. METHODS: Matched CHF patients were given open-label RAN (1000 mg po-bid) added to guideline-driven therapy (RANCHF, 41 systolic, 13 diastolic) or no adjuvant therapy (control, NORANCHF, 43 systolic, 12 diastolic). Echocardiographic LVEF and P&S measures were obtained at baseline and follow-up (mean 23.7 months). RESULTS: LVEF increased in 70% of RANCHF patients, an average of 11.3 units. Mean LVEF remained unchanged in NORANCHF patients. P&S measures indicated cardiovascular autonomic neuropathy (P<=0.1 bpm(2)) in 20% of NORANCHF patients at baseline and in 29% at follow-up (increasing in both groups). At baseline, 28% of patients had high sympathovagal balance (SB), RAN normalized SB over 50% of these; in contrast, the NORANCHF group had a 20% increase in patients with high SB. CONCLUSIONS: RAN preserves or improves LVEF and decreases high SB in CHF. PMID- 27004102 TI - Use of a "CNI holidays" strategy in acute renal dysfunction late after heart transplant. Report of two cases. AB - BACKGROUND: Acute renal dysfunction (ARD) may appear in heart transplant (HTx) patients both in the early postoperative period and during follow-up, even after several years. CD25 is a subunit of the interleukin-2 receptor which is found exclusively on activated CD4 T lymphocytes. CD25 is crucial for clonal expansion of anti-allograft host lymphocytes that mediate in acute rejection. There are experiences supporting the use of Anti-CD25 monoclonal antibodies (MAb) immediately after HTx in patients with ARD as a bridge to renal function recovery, allowing the temporary suspension of treatment with CNI. METHODS: In this study we report two cases of successful use of weekly MAb (basiliximab) in HTx patients who developed late ARD after HTx. CONCLUSIONS: In coclusion, we think that in cases of ARD where CNI therapy plays a key role, the use of weekly doses of basiliximab allows CNI discontinuation until the restoration of renal function is achieved. PMID- 27004104 TI - Multivariate modeling of settling depth of apple fruit (Red Delicious variety) in water. AB - Settling depth of apple was determined by a water column and a digital camera. The depth was experimentally modeled using multivariate regression using a coded program in MATLAB software. The best models were based on the density, dropping height volume/mass with coefficient of determination and mean square error of 0.90 and 4.08, respectively. PMID- 27004103 TI - Alterations to mTORC1 signaling in the skeletal muscle differentially affect whole-body metabolism. AB - BACKGROUND: The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. RESULTS: We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively. Ten-week old RAmKO mice are lean and insulin resistant with increased energy expenditure, and they are resistant to a high-fat diet (HFD). This correlates with an increased expression of histone deacetylases (HDACs) and a downregulation of genes involved in glucose and fatty acid metabolism. Ten-week-old TSCmKO mice are also lean, glucose intolerant with a decreased activation of protein kinase B (Akt/PKB) targets that regulate glucose transporters in the muscle. The mice are resistant to a HFD and show reduced accumulation of glycogen and lipids in the liver. Both mouse models suffer from a myopathy with age, with reduced fat and lean mass, and both RAmKO and TSCmKO mice develop insulin resistance and increased intramyocellular lipid content. CONCLUSIONS: Our study shows that alterations of mTORC1 signaling in the skeletal muscle differentially affect whole-body metabolism. While both inhibition and constitutive activation of mTORC1 induce leanness and resistance to obesity, changes in the metabolism of muscle and peripheral organs are distinct. These results indicate that a balanced mTORC1 signaling in the muscle is required for proper metabolic homeostasis. PMID- 27004105 TI - The effects of protein isolates and hydrocolloids complexes on dough rheology, physicochemical properties and qualities of gluten-free crackers. AB - To understand the suitability of protein-hydrocolloid complexes as replacement for wheat protein in rice crackers, and the effect of protein source, carboxylmethylcellulose (CMC) and hydroxylpropylmethylcellulose (HPMC) at 1.0%, 1.5%, and 2.0% w/w, and 0.25%, 0.50%, and 0.75% w/w of xanthan gum (XN) were added to flour-blendedrice crackers (FF). A variety of protein isolates was added to 2.5%, 5.0%, and 10% w/w combinations of protein isolates and hydrocolloids were investigated. The controls were FF, 100% rice crackers (RF), and wheat crackers (WF). About 1.5% CMC samples had the closest hardness to WF, followed by 0.5%XN and 1.5%HPMC, and 0.5%XN crackers had the highest moisture content and water activities followed by 0.75%XN, 1.5%CMC, and 1.5%HPMC. Increasing % of hydrocolloids also increased puffiness. Protein isolate crackers had higher moisture content and water activity. Protein isolates improved puffiness. Whey protein improved elasticity, while hydrocolloids added to leguminous protein increased loss tangent. PMID- 27004106 TI - Influence of extraction methods on antioxidant and antimicrobial properties of essential oil from Thymua danesis subsp. Lancifolius. AB - The essential oil (EO) from dried ground powder leaves and stems of Thymua danesis was extracted using hydrodistillation (HD), ohmic extraction (OE), ultrasound-assisted HD and ultrasound-assisted OE methods. Then, the antioxidant, antimicrobial, and sensory properties of the EO were investigated both in vitro and in food systems. Thyme EO extracted by ultrasound-assisted HD method had promising antibacterial activities against Escherichia coli and Staphylococcus aureus and had the best antioxidant properties when tested in vitro. In food systems, higher concentrations of the EO were needed to exert similar antibacterial and antioxidant effects. Furthermore, thyme EO added yogurt and drink yogurt revealed better sensory properties than the control and fresh samples. Essential oil from Thymua danesis has a good potential to be used as an antioxidant, antimicrobial, and flavoring agent in food systems and the extraction method effects on the antioxidant and antimicrobial properties of the thyme extract. PMID- 27004107 TI - Effect of freeze-thaw cycles on the nutritional quality of some selected Nigerian soups. AB - Freezing and thawing are heat transfer processes, involving chemical changes which may greatly affect product quality. Due to sparse literature on freeze thawed cycles and its effects on soups quality, the effect of freeze-thaw cycles on the nutritional quality of selected Nigerian soups has to be investigated. Soups (Ila, Ewedu, Ogbono, and Kuka) were prepared using standard recipes. The soups were packaged in plastic and aluminum containers, frozen at -20 degrees C, and thawed with microwave oven, hot water (100 degrees C), and at ambient condition for four cycles of 5-day interval. After each cycle, chemical compositions of the samples were determined using AOAC methods. Data were analyzed using ANOVA at P = 0.05. Moisture, protein, fat, crude fiber, ash, and carbohydrate contents of the freeze-thawed soups were 63.6-88.6%, 3.6-8.8%, 1.0 6.1%, 0.8-1.2%, 1.8-4.6%, and 0.9-15.6%, respectively. Mineral contents were iron (5.0-6.8 mg/100 g), calcium (68.1-190.8 mg/100 g), sodium (144.4-231.7 mg/100 g), potassium (200.4-302.1 mg/100 g), and phosphorus (228.0-337.2 mg/100 g). Vitamins were vitamin A (29.5-59.9 mg/100 g), vitamin B (10.1-36.4 mg/100 g), and vitamin E (28.4-90.2 mg/100 g). Microwave-thawed plastic soups had limited nutritional losses when compared with other thawing methods, and should not be extended beyond the third cycle because of increasing reduction in fat and protein, indicating deterioration. PMID- 27004108 TI - Effect of green Spanish-style Manzanilla packaging conditions on the prevalence of the putative probiotic bacteria Lactobacillus pentosus TOMC-LAB2. AB - This work focuses on the persistence of the putative probiotic bacteria Lactobacillus pentosus TOMC-LAB2 on green Spanish-style Manzanilla olives according to different packaging conditions and storage temperatures. The lactic acid bacteria population decreased with time but the highest survival counts (and lowest yeasts) at the end of storage (8 months) were observed in plastic pouches under nitrogen atmosphere and glass jars with brine stored at 20 degrees C. Molecular techniques showed a 100% presence of the putative probiotic bacteria in biofilms adhered to olive epidermis, while it was absent in PPB (plastic pouches with brine) and in olives stored at 7 degrees C. No changes in NaCl, pH or combined acidity were observed during the storage except for a slight increase in titratable acidity at 20 degrees C. The color of the fruits was stable but degraded at 20 degrees C for olives in plastic pouches with brine. PMID- 27004109 TI - Screening of microorganisms from Antarctic surface water and cytotoxicity metabolites from Antarctic microorganisms. AB - The Antarctic is a potentially important library of microbial resources and new bioactive substances. In this study, microorganisms were isolated from surface water samples collected from different sites of the Antarctic. 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay-based cytotoxicity tracking method was used to identify Antarctic marine microorganism resources for antitumor lead compounds. The results showed that a total of 129 Antarctic microorganism strains were isolated. Twelve strains showed potent cytotoxic activities, among which a Gram-negative, rod-shaped bacterium, designated as N11 8 was further studied. Phylogenetic analysis based on 16S rRNA gene sequence showed that N11-8 belongs to the genus Bacillus. Fermented active products of N11 8 with molecular weights of 1-30 kDa had higher inhibitory effects on different cancaer cells, such as BEL-7402 human hepatocellular carcinoma cells, U251 human glioma cells, RKO human colon carcinoma cells, A549 human lung carcinoma cells, and MCF-7 human breast carcinoma cells. However, they displayed lower cytotoxicity against HFL1 human normal fibroblast lung cells. However, they displayed lower cytotoxicity against HFL1 human normal fibroblast lung cells. Microscopic observations showed that the fermented active products have inhibitory activity on BEL-7402 cells similar to that of mitomycin C. Further studies indicated that the fermented active products have high pH and high thermal stability. In conclusion, most strains isolated in this study may be developed as promising sources for the discovery of antitumor bioactive substances. The fermented active products of Antarctic marine Bacillus sp. N11- 8 are expected to be applied in the prevention and treatment of cancer. PMID- 27004110 TI - Sensory quality of soymilk and tofu from soybeans lacking lipoxygenases. AB - The oxidation of unsaturated lipids by lipoxygenases in soybeans causes undesirable flavors in soy foods. Using a traditional and a nontraditional soy food user group, we examined the cultural difference in perceiving the sensory characteristics of soymilk and tofu produced from soybeans with or without lipoxygenases (Lx123). The two groups described the samples using similar terms. The traditional users preferred the control soy milk and lipoxygenase-free tofu while the nontraditional users preferred the lipoxygenase-free soymilk with no preference for tofu. In a separate study, a trained descriptive taste panel compared the odor of soymilk and tofu from control soybeans or those lacking lipoxygenase-1 and lipoxygenase-2 (Lx12) or all three isomers (Lx123). The rancid/grassy odor was rated the lowest in Lx123 products, followed by Lx12 products with the control products given the highest rating. The Lx12 and Lx123 products were also sweeter and less bitter than the controls. Taken together, our results demonstrated that soybeans lacking lipoxygenases can produce soy foods with less undesirable aromas and are therefore likely more acceptable to the consumers. PMID- 27004111 TI - Comparing the effect of encapsulated and unencapsulated fennel extracts on the shelf life of minced common kilka (Clupeonella cultriventris caspia) and Pseudomonas aeruginosa inoculated in the mince. AB - The quality of minced kilka (Clupeonella cultriventris caspia) with gum arabic encapsulated (0.3% and 0.5% w/w) and unencapsulated fennel extract (FE) (0.3% and 0.5% w/w) stored at 4 degrees C was examined over a storage period of 15 days. The control and the treated fish samples were analyzed periodically for microbiological (total viable count [TVC] and total psychrotrophic count [TPC]) and chemical (peroxide value (PV) and total volatile nitrogen (TVB-N)) parameters. Also the inhibitory effect of encapsulated and unencapsulated FE was evaluated against Pseudomonas aeruginosa, inoculated in minced kilka. According to the results, encapsulated FE samples showed the lowest amount of lipid oxidation and microbial deterioration during the storage period compared with the control and pure extract treatments. Although, the encapsulated FE at 0.5% showed drastic bacterial effect against Pseudomonas aeruginosa compared to others. Generally, gum arabic encapsulation could help to obtain higher antimicrobial and antioxidant activity in lower FE concentrations in minced fish. PMID- 27004112 TI - Proximate, mineral, and antinutrient compositions of indigenous Okra (Abelmoschus esculentus) pod accessions: implications for mineral bioavailability. AB - The promotion and consumption of indigenous vegetables could help to mitigate food insecurity and alleviate malnutrition in developing countries. Nutrient and antinutrient compositions of eight accessions of Okra Pods were investigated. Molar ratios and mineral bioavailability of Okra pod accessions were also calculated and compared to the critical values to predict the implications for mineral bioavailability. Proximate and mineral composition of Okra pod accessions were determined using standard methods of Association of Official Analytical Chemists. The result of the study revealed that the proximate composition (g/100 g) in dry weight basis was significantly (P < 0.05) varied and ranged: moisture/dry matter 9.69-13.33, crude protein 10.25-26.16, crude fat 0.56-2.49, crude fiber 11.97-29.93, crude ash 5.37-11.30, utilizable carbohydrate 36.66 50.97, and gross energy 197.26-245.55 kcal/100 g. The mineral concentrations (mg/100 g) were also significantly (P < 0.05) varied and ranged: calcium (111.11 311.95), Iron (18.30-36.68), potassium (122.59-318.20), zinc (3.83-6.31), phosphorus (25.62-59.72), and sodium (3.33-8.31) on dry weight bases. The Okra Pods of "OPA#6" accession contained significantly higher amounts of crude protein, total ash, crude fat, calcium, iron, and zinc than all other accessions evaluated in this study. The results of antinutrients analysis showed that, except phytate, tannin, and oxalate contents of all the accessions were significantly (P < 0.05) varied. The range of phytate, tannin, and oxalate contents (mg/100 g) for Okra pod accessions studied were as follows: 0.83-0.87, 4.93-9.90, and 0.04-0.53, respectively. The calculated molar ratios of phytate: calcium, phytate: iron, phytate: zinc, oxalate: calcium and [Phytate][Calcium]/[Zinc] were below the critical value and this indicate that the bioavailability of calcium, iron, and zinc in these accessions could be high. The results of the study revealed that Okra pod contain appreciable amount of vital nutrients like protein, fiber, calcium, iron, and zinc and low in antinutrient contents with high mineral bioavailability. Therefore, increase in the production and consumption of these nutrient-rich indigenous Okra pods will help to supplement/formulate the diets and alleviate the problems associated with malnutrition in the country. PMID- 27004115 TI - Optimization of the marinating conditions of cassava fish (Pseudotolithus sp.) fillet for Lanhouin production through application of Doehlert experimental design. AB - Lanhouin is a traditional fermented salted fish made from the spontaneous and uncontrolled fermentation of whole salted cassava fish (Pseudotolithus senegalensis) mainly produced in the coastal regions of West Africa. The combined effects of NaCl, citric acid concentration, and marination time on the physicochemical and microbiological characteristics of the fish fillet used for Lanhouin production were studied using a Doehlert experimental design with the objective of preserving its quality and safety. The marination time has significant effects on total viable and lactic acid bacteria counts, and NaCl content of the marinated fish fillet while the pH was significantly affected by citric acid concentration and marination duration with high regression coefficient R (2) of 0.83. The experiment showed that the best conditions for marination process of fish fillet were salt ratio 10 g/100 g, acid citric concentration 2.5 g/100 g, and marination time 6 h. These optimum marinating conditions obtained present the best quality of marinated flesh fish leading to the safety of the final fermented product. This pretreatment is necessary in Lanhouin production processes to ensure its safety quality. PMID- 27004114 TI - Alteration of starch hydrolyzing enzyme inhibitory properties, antioxidant activities, and phenolic profile of clove buds (Syzygium aromaticum L.) by cooking duration. AB - This study assessed the effect of cooking duration on starch hydrolyzing enzyme (alpha-amylase and alpha-glucosidase) activities, antioxidant (1,1-diphenyl-2 picrylhydrazyl [DPPH*], hydroxyl [OH*] radicals scavenging abilities and reducing power) properties, and phenolic profile of clove buds. Clove buds (raw) were cooked for 10 (SC 10) and 20 min (SC 20) and subsequently, their effects were assessed on enzyme activities, antioxidant properties, and phenolic profile. Inhibition of alpha-amylase and alpha-glucosidase activities and radicals scavenging abilities were altered by cooking in the trend; raw < SC 10 > SC 20, with IC 50 values ranging from 0.25 to 0.52 mg/mL and 0.10 to 1.50 mg/mL respectively. HPLC phenolic profile of the clove buds revealed significant (P < 0.05) changes in the amount of chlorogenic acid, quercitrin, quercetin, and kaempferol at different cooking duration. Thus, cooking duration may alter the phenolic compositions and nutraceutical potentials of clove bud by activation and/or deactivation of redox-active metabolites. PMID- 27004113 TI - Maillard reaction products and potatoes: have the benefits been clearly assessed? AB - Cooking foods affords numerous food safety benefits. During heating, Maillard reaction products (MRPs) are formed. MRPs contribute sensory aspects to food, including color, taste, and texture. One MRP, acrylamide, has been implicated in negative health outcomes; however, emerging data suggests MRPs may also deliver certain health benefits. The food industry has taken steps to decrease acrylamide formation, but the perception that high levels of acrylamide compromise the nutritional benefit of certain foods has continued. Potatoes are susceptible to MRP formation during cooking but also are considered an affordable, high nutrient content food. In particular, potatoes contribute significantly to fiber and potassium intakes in the U.S. population, two nutrients of need. How, then, should potatoes be judged for effects on health? A structured evidence assessment was conducted to identify literature, specifically clinical trials, on MRPs from potatoes and health, as well as nutritional contribution of potatoes. The results indicate limited human clinical data are available on negative health outcomes of potato-based MRPs, whereas potatoes are important contributors of key nutrients, such as fiber and potassium. Therefore, a balanced benefit-risk approach is warranted in order to assure that decreasing consumption of certain foods, like potatoes, does not lead to unintended consequences of nutrition inadequacies. PMID- 27004116 TI - Prediction of meat spectral patterns based on optical properties and concentrations of the major constituents. AB - A simulation method for approximating spectral signatures of minced meat samples was developed depending on concentrations and optical properties of the major chemical constituents. Minced beef samples of different compositions scanned on a near-infrared spectroscopy and on a hyperspectral imaging system were examined. Chemical composition determined heuristically and optical properties collected from authenticated references were simulated to approximate samples' spectral signatures. In short-wave infrared range, the resulting spectrum equals the sum of the absorption of three individual absorbers, that is, water, protein, and fat. By assuming homogeneous distributions of the main chromophores in the mince samples, the obtained absorption spectra are found to be a linear combination of the absorption spectra of the major chromophores present in the sample. Results revealed that developed models were good enough to derive spectral signatures of minced meat samples with a reasonable level of robustness of a high agreement index value more than 0.90 and ratio of performance to deviation more than 1.4. PMID- 27004117 TI - Explicit numerical solutions of a microbial survival model under nonisothermal conditions. AB - Differential equations used to describe the original and modified Geeraerd models were, respectively, simplified into an explicit equation in which the integration of the specific inactivation rate with respect to time was numerically approximated using the Simpson's rule. The explicit numerical solutions were then used to simulate microbial survival curves and fit nonisothermal survival data for identifying model parameters in Microsoft Excel. The results showed that the explicit numerical solutions provided an easy way to accurately simulate microbial survival and estimate model parameters from nonisothermal survival data using the Geeraerd models. PMID- 27004118 TI - Application of hydrolyzed proteins of animal origin in processed meat. AB - With increasing consumer interest in functional foods, proteins from slaughterhouse side streams can offer interesting application opportunities in this respect. Worldwide, increasing numbers of people are suffering from hypertension and protein deficiency. Hydrolyzed proteins of animal origin may show ACE-inhibitory activity, which is central to the treatment of hypertension. Furthermore, the protein content of, for example, meat products increases markedly through the addition of hydrolyzed proteins, and these protein-rich products are of interest to those suffering from protein deficiency. Through a series of analyses, six selected hydrolysates were analyzed for their application potential in the Danish meat product saveloy. Hydrolyzed pig rectum and bovine diaphragm showed the highest ACE-inhibitory activities, and these activities were maintained in the processed saveloys. The ACE-inhibitory activities could not readily be explained by the amino acid profile. The content of N-compounds in the saveloys increased with increasing addition of hydrolysate, with little difference between the added hydrolysates. A sensory panel assessed the saveloys with added porcine rectum (8%), bovine diaphragm (8%), and bovine heart (4% and 8%) as having the strongest off-flavors (chemical flavor). No increase in salty taste resulting from the addition of hydrolysates was detected in the saveloys. Finally, the consumers found the saveloys too mild in flavor and recommended the addition of more spices. PMID- 27004119 TI - The effect of encapsulated fennel extracts on the quality of silver carp fillets during refrigerated storage. AB - The effect of fennel extract on the quality of silver carp (Hypophthalmicthys molitrix) fillets, and the possible efficacy of liposomal encapsulation in the improvement of its antimicrobial and antioxidant activity during chilled storage (4 + 1 degrees C) of the fillets were examined over a period of 15 days. Silver carp fillets were treated with pure fennel extract (0.3% and 0.5% w/v) and liposomal encapsulated fennel extract (0.3% and 0.5% w/v), and their quality changes in terms of total volatile basic nitrogen (TVB-N), peroxide value (PV), thiobarbituric acid (TBA), microbial counts, and sensory properties were investigated. Fennel extract could retard the deterioration of silver carp fillets, as reflected in lower TVB-N, PV and TBA value. Moreover, the efficacy of fennel extract was improved when it was encapsulated into liposome. Silver carp fillets treated with the encapsulated fennel extract showed the lowest amount of lipid oxidation and microbial deterioration during the storage period compared with the control and pure extract treatments. Sensory evaluation revealed that shelf life of silver carp fillet was longest for samples treated with encapsulated fennel extract at 0.5% (15 days), as compared to the control (6 days) (P < 0.05). PMID- 27004120 TI - Effects of maturity on physicochemical properties of Gac fruit (Momordica cochinchinensis Spreng.). AB - The aril around the seeds of Gac fruit is rich in fatty acids and carotenoids (lycopene and beta-carotene). Understanding how these qualities are affected by fruit maturity at harvest may identify indices for quality assessment. Some physical and chemical properties of Gac fruit were determined for fruit harvested between 8 and 16 weeks after pollination (WAP). Fruit respiration rates and ethylene production rates were assessed after harvest and up to 20 days in storage at 20 degrees C. Fruit harvested at 14 WAP had the highest oil (0.27 +/- 0.02 g/g DW), lycopene content (0.45 +/- 0.09 mg/g FW), and beta-carotene content (0.33 +/- 0.05 mg/g FW) which declined by 16 WAP. External skin color and aril TSS were indicative of oil and carotenoid contents in aril. Skin color, TSS and potentially firmness were good indices of fruit quality. Harvesting less mature fruit at 12 WAP would be practical as the fruit were firmer and more capable of transport; however, quality during postharvest ripening may be limited. Fruits continued to ripen after they were harvested and an ethylene peak in the least mature fruit may reflect a climacteric behavior but this needs further investigation. PMID- 27004121 TI - Development and quality characteristics of shelf-stable soy-agushie: a residual by-product of soymilk production. AB - A process was developed for the production of a high-protein food ingredient, soy agushie, from the residual by-product of soymilk production. The product, with a moisture content of about 6%, was evaluated for its quality characteristics and performance in traditional dishes. The protein content was about 26% with similar amino acids content as that of the whole soybean. Lysine remained high in the dehydrated product (6.57 g/16 g N). While over 60% of the original B vitamins content in the beans was extracted with the milk, high proportions of the minerals were found to be retained in the residual by-product. The process adequately reduced the trypsin inhibitor levels in the beans from 25 to 1.5 mg/g. High sensory scores were obtained for recipes developed with soy-agushie in traditional dishes. The scope of utilization of the soy-agushie could be widened to include several traditional foods and bakery products for maximum nutritional benefits. PMID- 27004122 TI - Glycemic responses to maize flour stiff porridges prepared using local recipes in Malawi. AB - Glycemic index is defined as the incremental area under the blood glucose response curve of a 50 g carbohydrate portion of a test food expressed as a percent of the response to the same amount of carbohydrate from a standard food taken by the same subject. This study investigated glycemic index of maize stiff porridges consumed as staple food in Malawi and a large majority of other countries in sub-Saharan Africa to identify areas for improvement in consumer diets. Stiff porridges were prepared using flour from whole maize, maize grits, and fermented maize grits. The porridges were served to 11 healthy volunteers for 3 weeks, with two serving sessions a week. Glucose was served as a reference food during weekly serving sessions. Results from descriptive analysis revealed that glycemic responses varied across subjects and porridge types. Porridge prepared from fermented maize grits had moderate glycemic index of 65.49 and was comparable in nutrient composition and sensory characteristics with the other test porridges. Glycemic indices of the porridges prepared from whole maize flour and grits were high at 94.06 and 109.64, respectively, attributed to the effect of traditional maize flour processing, preparation, and cooking methods used. The study also calculated glyaemic load of the porridges and drew recommendations to inform diet planning and modifications for healthy and diabetic individuals. PMID- 27004123 TI - Nutritional composition of raw fresh cashew (Anacardium occidentale L.) kernels from different origin. AB - The total dietary fiber, sugar, protein, lipid profile, sodium, and energy contents of 11 raw cashew kernel (Anacardium occidentale L.) samples from India, Brazil, Ivory Coast, Kenya, Mozambique, and Vietnam were determined. Total fat was the major component accounting for 48.3% of the total weight, of which 79.7% were unsaturated FA (fatty acids), 20.1% saturated FA, and 0.2% trans FA. Proteins, with 21.3 g/100 g, were ranked second followed by carbohydrates (20.5 g/100 g). The average sodium content was 144 mg/kg. Fourteen FA were identified among which oleic acid was the most abundant with a contribution of 60.7% to the total fat, followed by linoleic (17.77%), palmitic (10.2%), and stearic (8.93%) acids. The mean energy content was 2525 kJ/100g. Furthermore, the sterol profile and content, amino acids, vitamins, and minerals of four raw cashew kernel samples from Brazil, India, Ivory Coast, and Vietnam were determined. beta Sitosterol with 2380 +/- 4 mg/kg fat was the most occurring sterol. Glutamic acid, with 4.60 g/100 g, was the amino acid with highest presence, whereas tryptophan with 0.32 g/100 g was the one with lower presence. Vitamin E with an average contribution of 5.80 mg/100 g was the most abundant vitamin. Potassium with a mean value of 6225 mg/kg was the mineral with highest amount in cashew samples. PMID- 27004124 TI - Profiling cancer metabolism at the 'omic' level: a last resort or the next frontier? PMID- 27004125 TI - Does homeopathic medicine have a preventive effect on respiratory tract infections? A real life observational study. AB - BACKGROUND: Homeopathic medicine is a branch of integrative medicine that has been gaining increasing popularity. However, its clinical application remains controversial. To improve the understanding of homeopathy, observational studies which monitor the effects of homeopathy in real-life clinical settings-are a helpful adjunct to randomized controlled trials. The goal of this controlled observational study was to investigate the role of the homeopathic medicine in preventing respiratory tract infections (RTIs). METHODS: This retrospective analysis of patients' medical records focused on a single centre from 2002 to 2011, and examined 459 patients, out of whom 248 were treated with homeopathic medicine (specific extract of duck liver and heart) and 211 were not treated. All patients were followed-up for at least 1 year, and up to a maximum of 10 years. RESULTS: A significant reduction in the frequency of onset of RTIs was found in both the homeopathic medicine and untreated groups. The reduction in the mean number of RTI episodes during the period of observation vs. the year before inclusion in the study was significantly greater in the homeopathic-treated group than in untreated patients (-4.76 +/- 1.45 vs. -3.36 +/- 1.30; p = 0.001). The beneficial effect of the homeopathic medicine was not significantly related to gender, age, smoking habits or concomitant respiratory diseases when compared to the effect observed in untreated patients. CONCLUSION: These results suggest that homeopathic medicine may have a positive effect in preventing RTIs. However, randomized studies are needed before any firm conclusion can be reached. PMID- 27004126 TI - The different interactions of Colletotrichum gloeosporioides with two strawberry varieties and the involvement of salicylic acid. AB - The disease symptoms recognized as 'Anthracnose' are caused by Colletotrichum spp. and lead to large-scale strawberry (Fragaria*ananassa Duchesne) losses worldwide in terms of both quality and production. Little is known regarding the mechanisms underlying the genetic variations in the strawberry-Colletotrichum spp. interaction. In this work, Colletotrichum gloeosporioides (C. gloeosporioides) infection was characterized in two varieties exhibiting different susceptibilities, and the involvement of salicylic acid (SA) was examined. Light microscopic observation showed that C. gloeosporioides conidia germinated earlier and faster on the leaf surface of the susceptible cultivar compared with the less-susceptible cultivar. Several PR genes were differentially expressed, with higher-amplitude changes observed in the less-susceptible cultivar. The less-susceptible cultivar contained a higher level of basal SA, and the SA levels increased rapidly upon infection, followed by a sharp decrease before the necrotrophic phase. External SA pretreatment reduced susceptibility and elevated the internal SA levels in both varieties, which were sharply reduced in the susceptible cultivar upon inoculation. The less-susceptible cultivar also displayed a more sensitive and marked increase in the transcripts of NB-LRR genes to C. gloeosporioides, and SA pretreatment differentially induced transcript accumulation in the two varieties during infection. Furthermore, SA directly inhibited the germination of C. gloeosporioides conidia; NB-LRR transcript accumulation in response to SA pretreatment was both dose- and cultivar dependent. The results demonstrate that the less-susceptible cultivar showed reduced conidia germination. The contribution of SA might involve microbial isolate-specific sensitivity to SA, cultivar/tissue-specific SA homeostasis and signaling, and the sensitivity of R genes and the related defense network to SA and pathogens. PMID- 27004127 TI - Overweight and abdominal obesity as determinants of undiagnosed diabetes and pre diabetes in Bangladesh. AB - BACKGROUND: Type 2 diabetes and pre-diabetes are an increasing pandemic globally and often remain undiagnosed long after onset in low-income settings. The objective of this study is to assess the determinants and prevalence of undiagnosed diabetes and pre-diabetes among adults in Bangladesh. METHODS: In an exploratory study, we performed oral glucose tolerance test on 1243 adults >=20 years of age from urban Mirpur, Dhaka (n = 518) and rural Matlab, Chandpur (n = 725) who had never been diagnosed with diabetes or pre-diabetes. We collected data on socioeconomic, demographic, past medical history, physical activity, and measured weight, height, waist and hip circumferences, and blood pressure. Risk factors associated with undiagnosed diabetes and pre-diabetes were examined using a multiple logistic regression model. RESULTS: Overall prevalence of diabetes and pre-diabetes was 6.6 % (95 % CI 5.3, 8.1) and 16.6 % (14.5, 18.7) respectively, with both being significantly higher in urban than rural populations (diabetes 12.2 % vs 2.6 % respectively, p < 0.000; pre-diabetes 21.2 % vs 13.2 %, p < 0.001). After adjustment the variables, urban residence (OR 2.5 [95 % CI 1.02, 5.9]), age group 40-59 y (2.9 [1.7-5.2]), >=60 y (8.1 [2.8-23.8]), overweight (2.2 [1.3-3.9]), abdominal obesity (3.3 [1.8-6.0]) and high WHR 5.6 (2.7-11.9) were all significant predictors of diabetes. Significant predictors of pre diabetes included age group 40-59 (1.6 [1.1-2.2]), female sex (1.5 [1.0-2.2]), abdominal obesity (1.7 [1.2-2.4]) and high WHR (1.6 [1.2-2.3]). CONCLUSION: Both overweight and abdominal obesity contribute to the hidden public health threat of undiagnosed diabetes and pre-diabetes. Awareness raising and screening of high risk groups combined with a tailored approach are essential for halting the epidemic of diabetes and pre-diabetes in Bangladesh. PMID- 27004128 TI - Evolution of visual art with dopaminergic therapy. AB - A patient with right-side-predominant Parkinson's disease presented visual artwork which improved in resemblance to the model which he was copying with increasing doses of levodopa. I propose that increased dopaminergic replacement resulted in improved attention to detail, mediated by circuitry in the left hemisphere. PMID- 27004129 TI - Inositol transporters AtINT2 and AtINT4 regulate arsenic accumulation in Arabidopsis seeds. AB - Arsenic contamination of groundwater and soils threatens the health of tens of millions of people worldwide. Understanding the way in which arsenic is taken up by crops such as rice, which serve as a significant source of arsenic in the human diet, is therefore important. Membrane transport proteins that catalyse arsenic uptake by roots, and translocation through the xylem to shoots, have been characterized in a number of plants, including rice. The transporters responsible for loading arsenic from the xylem into the phloem and on into the seeds, however, are yet to be identified. Here, we show that transporters responsible for inositol uptake in the phloem in Arabidopsis also transport arsenic. Transformation of Saccharomyces cerevisiae with AtINT2 or AtINT4 led to increased arsenic accumulation and increased sensitivity to arsenite. Expression of AtINT2 in Xenopus laevis oocytes also induced arsenite import. Disruption of AtINT2 or AtINT4 in Arabidopsis thaliana led to a reduction in phloem, silique and seed arsenic concentrations in plants fed with arsenite through the roots, relative to wild-type plants. These plants also exhibited a large drop in silique and seed arsenic concentrations when fed with arsenite through the leaves. We conclude that in Arabidopsis, inositol transporters are responsible for arsenite loading into the phloem, the key source of arsenic in seeds. PMID- 27004130 TI - An Asymptotically-Optimal Sampling-Based Algorithm for Bi-directional Motion Planning. AB - Bi-directional search is a widely used strategy to increase the success and convergence rates of sampling-based motion planning algorithms. Yet, few results are available that merge both bi-directional search and asymptotic optimality into existing optimal planners, such as PRM*, RRT*, and FMT*. The objective of this paper is to fill this gap. Specifically, this paper presents a bi directional, sampling-based, asymptotically-optimal algorithm named Bi directional FMT* (BFMT*) that extends the Fast Marching Tree (FMT*) algorithm to bidirectional search while preserving its key properties, chiefly lazy search and asymptotic optimality through convergence in probability. BFMT* performs a two source, lazy dynamic programming recursion over a set of randomly-drawn samples, correspondingly generating two search trees: one in cost-to-come space from the initial configuration and another in cost-to-go space from the goal configuration. Numerical experiments illustrate the advantages of BFMT* over its unidirectional counterpart, as well as a number of other state-of-the-art planners. PMID- 27004131 TI - Autografting of Renal Progenitor Cells Ameliorates Kidney Damage in Experimental Model of Pyelonephritis. AB - Current therapies for pyelonephritic renal damage have severe limitations; stem cells may offer an exciting potential in regenerating nephrology. We aimed to investigate the feasibility of direct intrarenal injection of autologous renal progenitor cells (RPCs; originated from epithelial cells in Bowman's capsule) in chronic pyelonephritis rat model. Twenty-seven rats were divided into three groups. The control group (GI, n = 3) underwent sham subcapsular injection of isotonic saline. Pyelonephritis was induced in the right kidney of the remaining 24 rats and isotonic saline (GII, n = 12) or labeled autologous RPCs, obtained from a biopsy of left kidney (GIII, n = 12), were injected into the subcapsular space 6 weeks later. At 7, 14, 28, and 60 days, dimercaptosuccinic acid scan was performed in three animals of each group at every interval and subsequently renal sections were obtained for the evaluation of tubular and glomerular regeneration and proliferation. Cell transplantation resulted in the reduction of tubular and glomerular atrophy after 2 weeks. The transplanted cells were observed in the reconstructed region of the kidneys as evidenced by the presence of fluorescently labeled cells both in tubules and glomeruli. We also observed significant decrease in interstitial fibrosis in the fourth week and there were higher amount of Ki-67-positive cells in GIII. Notably, the right renal tissue integrity was significantly improved in this group and revealed normal cortical function on day 60. Transplanting RPCs showed the potential for partial augmentation of kidney structure and function in pyelonephritis. Cellular repair was seen predominantly in the proximal tubule, the major site of injury in pyelonephritis. Our findings may pave the way toward the future regeneration of renal scarring of pyelonephritis in children. PMID- 27004132 TI - Monitoring of Liver Cell Transplantation in a Preclinical Swine Model Using Magnetic Resonance Imaging. AB - Liver cell transplantation (LCT) is a promising treatment approach for certain liver diseases, but clinical implementation requires methods for noninvasive follow-up. Labeling with superparamagnetic iron oxide particles can enable the detection of cells with magnetic resonance imaging (MRI). We investigated the feasibility of monitoring transplanted liver cells by MRI in a preclinical swine model and used this approach to evaluate different routes for cell application. Liver cells were isolated from landrace piglets and labeled with micron-sized iron oxide particles (MPIO) in adhesion. Labeled cells (n = 10), native cells (n = 3), or pure particles (n = 4) were transplanted to minipigs via intraportal infusion into the liver, direct injection into the splenic parenchyma, or intra arterial infusion to the spleen. Recipients were investigated by repeated 3.0 Tesla MRI and computed tomography angiography up to 8 weeks after transplantation. Labeling with MPIO, which are known to have a strong effect on the magnetic field, enabled noninvasive detection of cell aggregates by MRI. Following intraportal application, which is commonly applied for clinical LCT, MRI was able to visualize the microembolization of transplanted cells in the liver that were not detected by conventional imaging modalities. Cells directly injected into the spleen were retained, whereas cell infusions intra-arterially into the spleen led to translocation and engraftment of transplanted cells in the liver, with significantly fewer microembolisms compared to intraportal application. These findings demonstrate that MRI can be a valuable tool for noninvasive elucidation of cellular processes of LCT and-if clinically applicable MPIO are available-for monitoring of LCT under clinical conditions. Moreover, the results clarify mechanisms relevant for clinical practice of LCT, suggesting that the intra-arterial route to the spleen deserves further evaluation. PMID- 27004133 TI - Tracking Cells Without Leaving a Trace. PMID- 27004134 TI - Resident Endothelial Progenitor Cells From Human Placenta Have Greater Vasculogenic Potential Than Circulating Endothelial Progenitor Cells From Umbilical Cord Blood. AB - Endothelial colony-forming cells (ECFCs) isolated from umbilical cord blood (CBECFCs) are highly proliferative and form blood vessels in vivo. The purpose of this investigation was to isolate and characterize a population of resident ECFCs from the chorionic villi of term human placenta and provide a comparative analysis of their proliferative and vasculogenic potential with CBECFCs. ECFCs were isolated from umbilical cord blood and chorionic villi from placentas obtained by caesarean deliveries. Placental ECFCs (PECFCs) expressed CD144, CD31, CD105, and KDR and were negative for CD45 and CD34, consistent with other ECFC phenotypes. PECFCs were capable of 28.6 +/- 6.0 population doublings before reaching senescence (vs. 47.4 +/- 3.2 for CBECFCs, p < 0.05, n = 4). In single cell assays, 46.5 +/- 1.2% underwent at least one division (vs. 51.0 +/- 1.8% of CBECFCs, p = 0.07, n = 6), and of those dividing PECFCs, 71.8 +/- 0.9% gave rise to colonies of >500 cells (highly proliferative potential clones) over 14 days (vs. 69.4 +/- 0.7% of CBECFCs, p = 0.07, n = 9). PECFCs formed 5.2 +/- 0.8 vessels/mm(2) in collagen/fibronectin plugs implanted into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice, whereas CBECFCs formed only 1.7 +/- 1.0 vessels/mm(2) (p < 0.05, n = 4). This study demonstrates that circulating CBECFCs and resident PECFCs are identical phenotypically and contain equivalent quantities of high proliferative potential clones. However, PECFCs formed significantly more blood vessels in vivo than CBECFCs, indicating that differences in vasculogenic potential between circulating and resident ECFCs exist. PMID- 27004135 TI - Validation of Islet Transport From a Geographically Distant Isolation Center Enabling Equitable Access and National Health Service Funding of a Clinical Islet Transplant Program for England. AB - Islet transplantation has become established as a successful treatment for type 1 diabetes complicated by recurrent severe hypoglycemia. In the UK access has been limited to a few centrally located units. Our goal was to validate a quality assured system for safe/effective transport of human islets in the UK and to successfully undertake the first transplants with transported islets. Pancreases were retrieved from deceased donors in the north of England and transported to King's College London using two-layer method (TLM) or University of Wisconsin solution alone. Islets were isolated and transported back to Newcastle in standard blood transfusion or gas-permeable bags with detailed evaluation pre- and posttransport. In the preclinical phase, islets were isolated from 10 pancreases with mean yield of 258,000 islet equivalents. No significant differences were seen between TLM and University of Wisconsin solution organ preservation. A significant loss of integrity was demonstrated in islets shipped in gas-permeable bags, whereas sterility, number, purity, and viability were maintained in blood transfusion bags. Maintenance of secretory granules and glucose-stimulated insulin secretion was confirmed following transport. A Standard Operating Procedure enabling final pretransplant quality control from a simple side-arm sample was validated. Moreover, levels of insulin and cytokines in transport medium were low, enabling transplant without centrifugation/resuspension at the recipient site. Six clinical transplants of transported islets were undertaken in five recipients with 100% primary graft function and resolution of severe hypoglycemia. Safe and clinically effective islet transport has been established facilitating sustainable NHS funding of a clinical islet transplant program for the UK. PMID- 27004136 TI - The 30-Year Anniversary of Pediatric Neurology Briefs. AB - Over the past 30 years, Pediatric Neurology Briefs (PNB) has been published monthly as a continuing education service designed to expedite and facilitate review of current medical literature concerning pediatric neurology. PMID- 27004137 TI - Concussions in Collision Youth Sports. AB - Investigators from the University of Pittsburg, University of Arkansas, Lake Erie College of Osteopathic Medicine, and Boston Children's Hospital/Harvard Medical College researched the incidence of concussions in youth hockey in relation to age and activity setting. PMID- 27004138 TI - Cavernous Sinus Thrombosis in Children. AB - Investigators from the Children's Hospital of Philadelphia analyzed the clinical and radiographic findings in 12 cases of cavernous sinus thrombosis (CST) seen between 2000 and 2013, and conducted a literature search and review of the pooled data. PMID- 27004139 TI - Review of Prevention for Pediatric and Adolescent Migraine. AB - Authors from the Barrow Neurological Institute at Phoenix Children's Hospital present a narrative overview of preventive treatment for pediatric and adolescent migraine. PMID- 27004140 TI - Prognosis of Cyclic Vomiting Syndrome. AB - Investigators from Teikyo University School of Medicine, Tokyo, Japan, evaluated the clinical features, prognosis, and prophylaxis of cyclic vomiting syndrome and the relationship between the syndrome and levels of adrenocorticotropic/antidiuretic hormones (ACTH/ADH). PMID- 27004141 TI - Dystonia with MPH/Risperidone Combined Therapy for ADHD. AB - Investigators from Child Neurology and Pediatrics, University of Texas Health Science Center, Houston, report extrapyramidal symptoms in a 13-year-old boy with a psychiatric history of schizophrenia, bipolar disorder, ADHD, and autism, responsive to combination risperidone, oxcarbazepine, and MPH. PMID- 27004142 TI - Zika Virus Infection and Microcephaly. AB - A Task Force established by the Brazil Ministry of Health investigated the possible association of microcephaly with Zika virus infection during pregnancy and a registry for microcephaly cases among women suspected to have had Zika virus infection during pregnancy. PMID- 27004143 TI - Accounting for Posttraumatic Stress Disorder Symptom Severity With Pre- and Posttrauma Measures: A Longitudinal Study of Older Adults. AB - Using data from a longitudinal study of community-dwelling older adults, we analyzed the most extensive set of known correlates of PTSD symptoms obtained from a single sample to examine the measures' independent and combined utility in accounting for PTSD symptom severity. Fifteen measures identified as PTSD risk factors in published meta-analyses and 12 theoretically and empirically supported individual difference and health-related measures were included. Individual difference measures assessed after the trauma, including insecure attachment and factors related to the current trauma memory, such as self-rated severity, event centrality, frequency of involuntary recall, and physical reactions to the memory, accounted for symptom severity better than measures of pre-trauma factors. In an analysis restricted to prospective measures assessed before the trauma, the total variance explained decreased from 56% to 16%. Results support a model of PTSD in which characteristics of the current trauma memory promote the development and maintenance of PTSD symptoms. PMID- 27004144 TI - Goodness of fit to a mathematical model for Drosophila sleep behavior is reduced in hyposomnolent mutants. AB - The conserved nature of sleep in Drosophila has allowed the fruit fly to emerge in the last decade as a powerful model organism in which to study sleep. Recent sleep studies in Drosophila have focused on the discovery and characterization of hyposomnolent mutants. One common feature of these animals is a change in sleep architecture: sleep bout count tends to be greater, and sleep bout length lower, in hyposomnolent mutants. I propose a mathematical model, produced by least squares nonlinear regression to fit the form Y = aX (?) b, which can explain sleep behavior in the healthy animal as well as previously-reported changes in total sleep and sleep architecture in hyposomnolent mutants. This model, fit to sleep data, yields coefficient of determination R squared, which describes goodness of fit. R squared is lower, as compared to control, in hyposomnolent mutants insomniac and fumin. My findings raise the possibility that low R squared is a feature of all hyposomnolent mutants, not just insomniac and fumin. If this were the case, R squared could emerge as a novel means by which sleep researchers might assess sleep dysfunction. PMID- 27004145 TI - The yeast telomerase RNA, TLC1, participates in two distinct modes of TLC1-TLC1 association processes in vivo. AB - Telomerase core enzyme minimally consists of the telomerase reverse transcriptase domain-containing protein (Est2 in budding yeast S. cerevisiae) and telomerase RNA, which contains the template specifying the telomeric repeat sequence synthesized. Here we report that in vivo, a fraction of S. cerevisiae telomerase RNA (TLC1) molecules form complexes containing at least two molecules of TLC1, via two separable modes: one requiring a sequence in the 3' region of the immature TLC1 precursor and the other requiring Ku and Sir4. Such physical TLC1 TLC1 association peaked in G1 phase and did not require telomere silencing, telomere tethering to the nuclear periphery, telomerase holoenzyme assembly, or detectable Est2-Est2 protein association. These data indicate that TLC1-TLC1 associations reflect processes occurring during telomerase biogenesis; we propose that TLC1-TLC1 associations and subsequent reorganization may be regulatory steps in telomerase enzymatic activation. PMID- 27004146 TI - Low regeneration of lesions produced by coring in Orbicella faveolata. AB - The extraction of tissue-skeleton cores from coral colonies is a common procedure to study diverse aspects of their biology, water quality or to obtain environmental proxies. Coral species preferred for such studies in Caribbean reefs belong to the genera Orbicella. The long term effects of coring in the coral colony are seldom evaluated and in many Caribbean countries this practice is not regulated. We monitored 50 lesions produced on Orbicella faveolata colonies by the extraction of two centimeter-diameter cores to determine if they were able to heal after a four year period. At the end of the study 4% of the lesions underwent full regeneration, 52% underwent partial regeneration, 14% suffered additional tissue loss but remained surrounded by live tissue, and 30% merged with dead areas of the colonies. Given the low capacity of Orbicella faveolata to regenerate tissue-skeleton lesions, studies that use coring should be regulated and mitigation actions, such as using less destructive techniques and remediation measures after extraction, should be conducted to facilitate tissue regeneration. PMID- 27004147 TI - An explicit solution for calculating optimum spawning stock size from Ricker's stock recruitment model. AB - Stock-recruitment models have been used for decades in fisheries management as a means of formalizing the expected number of offspring that recruit to a fishery based on the number of parents. In particular, Ricker's stock recruitment model is widely used due to its flexibility and ease with which the parameters can be estimated. After model fitting, the spawning stock size that produces the maximum sustainable yield (S MSY) to a fishery, and the harvest corresponding to it (U MSY), are two of the most common biological reference points of interest to fisheries managers. However, to date there has been no explicit solution for either reference point because of the transcendental nature of the equation needed to solve for them. Therefore, numerical or statistical approximations have been used for more than 30 years. Here I provide explicit formulae for calculating both S MSY and U MSY in terms of the productivity and density dependent parameters of Ricker's model. PMID- 27004148 TI - The personality trait of behavioral inhibition modulates perceptions of moral character and performance during the trust game: behavioral results and computational modeling. AB - Decisions based on trust are critical for human social interaction. We judge the trustworthiness of partners in social interactions based on a number of partner characteristics as well as experiences with those partners. These decisions are also influenced by personality. The current study examined how the personality trait of behavioral inhibition, which involves the tendency to avoid or withdraw from novelty in both social and non-social situations, is related to explicit ratings of trustworthiness as well as decisions made in the trust game. In the game, healthy young adults interacted with three fictional partners who were portrayed as trustworthy, untrustworthy or neutral through biographical information. Participants could choose to keep $1 or send $3 of virtual money to a partner. The partner could then choose to send $1.5 back to the participant or to keep the entire amount. On any trial in which the participant chose to send, the partner always reciprocated with 50% probability, irrespective of how that partner was portrayed in the biography. Behavioral inhibition was assessed through a self-report questionnaire. Finally, a reinforcement learning computational model was fit to the behavior of each participant. Self-reported ratings of trust confirmed that all participants, irrespective of behavioral inhibition, perceived differences in the moral character of the three partners (trustworthiness of good > neutral > bad partner). Decisions made in the game showed that inhibited participants tended to trust the neutral partner less than uninhibited participants. In contrast, this was not reflected in the ratings of the neutral partner (either pre- or post-game), indicating a dissociation between ratings of trustworthiness and decisions made by inhibited participants. Computational modeling showed that this was due to lower initial trust of the neutral partner rather than a higher learning rate associated with loss, suggesting an implicit bias against the neutral partner. Overall, the results suggest inhibited individuals may be predisposed to interpret neutral or ambiguous information more negatively which could, at least in part, account for the tendency to avoid unfamiliar people characteristic of behaviorally inhibited temperament, as well as its relationship to anxiety disorders. PMID- 27004149 TI - Ship noise extends to frequencies used for echolocation by endangered killer whales. AB - Combining calibrated hydrophone measurements with vessel location data from the Automatic Identification System, we estimate underwater sound pressure levels for 1,582 unique ships that transited the core critical habitat of the endangered Southern Resident killer whales during 28 months between March, 2011, and October, 2013. Median received spectrum levels of noise from 2,809 isolated transits are elevated relative to median background levels not only at low frequencies (20-30 dB re 1 uPa(2)/Hz from 100 to 1,000 Hz), but also at high frequencies (5-13 dB from 10,000 to 96,000 Hz). Thus, noise received from ships at ranges less than 3 km extends to frequencies used by odontocetes. Broadband received levels (11.5-40,000 Hz) near the shoreline in Haro Strait (WA, USA) for the entire ship population were 110 +/- 7 dB re 1 uPa on average. Assuming near spherical spreading based on a transmission loss experiment we compute mean broadband source levels for the ship population of 173 +/- 7 dB re 1 uPa 1 m without accounting for frequency-dependent absorption. Mean ship speed was 7.3 +/ 2.0 m/s (14.1 +/- 3.9 knots). Most ship classes show a linear relationship between source level and speed with a slope near +2 dB per m/s (+1 dB/knot). Spectrum, 1/12-octave, and 1/3-octave source levels for the whole population have median values that are comparable to previous measurements and models at most frequencies, but for select studies may be relatively low below 200 Hz and high above 20,000 Hz. Median source spectrum levels peak near 50 Hz for all 12 ship classes, have a maximum of 159 dB re 1 uPa(2)/Hz @ 1 m for container ships, and vary between classes. Below 200 Hz, the class-specific median spectrum levels bifurcate with large commercial ships grouping as higher power noise sources. Within all ship classes spectrum levels vary more at low frequencies than at high frequencies, and the degree of variability is almost halved for classes that have smaller speed standard deviations. This is the first study to present source spectra for populations of different ship classes operating in coastal habitats, including at higher frequencies used by killer whales for both communication and echolocation. PMID- 27004150 TI - Symptomatic Anterior Cervical Osteophyte Causing Dysphagia: Case Report, Imaging, and Review of the Literature. AB - Anterior cervical osteophytes are found in 20-30% of elderly patients. Rarely, severe osteophytes can cause dysphagia, dysphonia, and dyspnea. Here, we illustrate a case of severe dysphagia caused by a large post-traumatic osteophyte with oropharyngeal swallow study showing a significant mass effect on the pharynx and resolution following osteophytectomy. We also review the literature regarding the etiology, diagnosis, and treatment of symptomatic anterior cervical osteophytes. PMID- 27004151 TI - Radiotherapy for Langerhans Cell Histiocytosis of Bilateral Eyelids. AB - Langerhans cell histiocytosis (LCH) is a rare disorder with numerous clinicopathological variants with differing clinical courses, treatment methods, and prognoses. We report one patient with atypical LCH of the bilateral lower eyelids and subsequent successful treatment with local radiation therapy. PMID- 27004152 TI - Cadaveric Analysis of the Kambin's Triangle. AB - Introduction Kambin's Triangle is a right triangle over the dorsolateral disc. The area of this right triangle currently serves as a strategic site of posterolateral, minimally invasive access to the nerve root for delivery of epidural steroid injections. This posterolateral approach has also been considered a safe area of access to the intervertebral disc space and, thus, an effective approach in reducing complications, such as violation of the thecal sac, the nerve root, or the bony elements of the spine during minimally invasive spinal surgery. No published studies have been performed to characterize the dimensions of the Kambin's Triangle. Our aim is to characterize its dimensions at the lumbar levels and determine its efficacy and safety as a site of access for minimally invasive spinal surgery. Methods Two randomly chosen adult male cadavers were used for this study. The measurements were made bilaterally at their lumbar levels (L1-L5), which equates to 16 total measurements (eight bilateral disc spaces on two cadavers). The disc space was first accessed using a Kirschner wire in a standard oblique approach. With the assistance of fluoroscopy, a Kirschner wire was passed into the disc through the Kambin's Triangle. The procedure was performed on the cadavers bilaterally at four levels, followed by open dissection. The calculations of the area were made by measuring the exiting nerve root, the superior border of the caudal vertebra, and the superior articulating facet-the borders of the Kambin's Triangle. Results The Kambin's Triangle height and width respectively averaged at 12 mm and 10 mm (L1 L2), 13 mm and 11 mm (L2-L3), 17 mm and 11 mm (L3-L4), and 18 mm and 12 mm (L4 L5). Thus, the area at each level was 60 mm(2) (L1-L2), 71.5 mm(2) (L2-L3), 93.5 mm(2) (L3-L4), and 108 mm(2) (L4-L5). All dissected levels demonstrated adequate anchoring of the Kirschner wire into the disc space with no evidence of nerve injury. Following this, a retractor was placed and complete discectomies were performed. All exiting nerves were protected in this safe zone and the thecal sac remained inviolate. Conclusion Understanding the Kambin's Triangle will assist surgeons in the minimally invasive approach to spinal surgeries, with potentially safe placement of interbody cages through this strategic space. PMID- 27004153 TI - Chronic Myeloid Leukemia: A Case of Extreme Thrombocytosis Causing Syncope and Myocardial Infarction. AB - Chronic myeloid leukemia (CML), a hematologic malignancy characterized by unregulated growth of myelogenous leukocytes, typically presents with symptoms of fatigue, anorexia, and splenomegaly. Laboratory studies often reveal a significant leukocytosis with neutrophilia. A moderate thrombocytosis may be present, but is not usually problematic. The following case discusses a patient who presented with syncope, a convulsive episode, and non ST-segment myocardial infarction secondary to symptomatic thrombocytosis of 2.5 million cells/microL. She was treated with plateletpheresis and subsequently experienced resolution of symptoms. Ultimately, a diagnosis of CML with an atypical presentation of the disease was identified in this patient. PMID- 27004154 TI - Severe Chest Wall Toxicity From Cryoablation in the Setting of Prior Stereotactic Ablative Radiotherapy. AB - We present the case of a 42-year-old woman with metastatic synovial sarcoma of parotid origin, treated definitively with chemoradiation, who subsequently developed oligometastatic disease limited to the lungs. She underwent multiple left and right lung wedge resections and left lower lobectomy, followed by right lower lobe stereotactic ablative radiotherapy (SABR), 54 Gy in three fractions to a right lower lobe lesion abutting the chest wall. Two years later, she was treated with cryoablation for a separate right upper lobe nodule abutting the chest wall. Two months later, she presented with acute shortness of breath, pleuritic chest pain, decreased peripheral blood O2 saturation, and productive cough. A computed tomography (CT) scan demonstrated severe chest wall necrosis in the area of recent cryoablation that, in retrospect, also received a significant radiation dose from her prior SABR. This case demonstrates that clinicians should exercise caution in using cryoablation when treating lung tumors abutting a previously irradiated chest wall. Note: Drs. Loo and Shah contributed equally as co-senior authors. PMID- 27004155 TI - KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer. AB - This is the case of an 84-year-old woman diagnosed with Stage IVb colon adenocarcinoma (CRC) metastatic to the liver, retroperitoneum, anastomotic site, and distal rectal sigmoid colon. She experienced intolerable side effects to systemic chemotherapy with 5-fluorouracil and bevacizumab, as well as disease progression. Next generation sequencing of her tumor was ordered, and further discussion of her malignancy's genomic information took place at a multidisciplinary molecular tumor board. The patient had mutations in KRAS (Kirsten rat sarcoma viral oncogene homolog) which made her ineligible for epidermal growth factor receptor (EGFR) inhibitors; however, a KDR p.R961W c.2881C>T mutation was noted as a variant of unknown significance (VUS). KDR (kinase insert domain receptor) is the human gene encoding for vascular endothelial growth factor receptor 2 (VEGFR-2). She was then considered a suitable candidate for regorafenib, which she could only tolerate at a low dose of 40 mg daily, with the intent of prolonging her survival and to optimize her quality of life. We report her excellent tolerance and exceptional response to low dose regorafenib, including symptomatic, tumor marker, and sustained partial metabolic radiological improvement. In the largest Phase III trial of regorafenib in CRC, only five patients (1%) of 760 experienced a partial response (versus one patient, 0.4%, receiving placebo). KDR R961W mutation has been described but no functional data has been reported. This mutation occurs in the tyrosine kinase domain of the VEGFR-2. Regorafenib targets VEGFR-2 (KDR). Hereby we hypothesize KDR mutation as a novel predictive biomarker to exceptional response to regorafenib in metastatic colorectal cancer. To our knowledge, this is the first reported case of the potential correlation between KDR mutation and regorafenib use for the successful management of a patient with advanced CRC, leading to what is considered an exceptional response. Further studies based on this preliminary data are warranted. PMID- 27004156 TI - Extensor Mechanism Disruption after Total Knee Arthroplasty: A Case Series and Review of Literature. AB - Extensor mechanism disruption following total knee arthroplasty (TKA) is a rare but devastating complication. These patients may require revision of the implants, but even then, it may not be possible to restore the normal function of the knee after the disruption. The patterns of extensor mechanism disruption can broadly be classified into three types: suprapatellar (quadriceps tendon rupture), transpatellar (patellar fracture), or infrapatellar (patellar tendon rupture). Infrapatellar tendon ruptures are the worst injuries, as they carry maximum morbidity and are challenging to manage. The disruption of the extensor mechanism may occur either intra-operatively or in the immediate postoperative period due to an injury. The treatment of extensor mechanism complications after TKA may include either nonsurgical management or surgical intervention in the form of primary repair or reconstruction with autogenous, allogeneic, or synthetic substitutes. We have provided an algorithm for the management of extensor mechanism disruption after TKA. PMID- 27004157 TI - Heterotopic Ossification Circumferentia Articularis (HOCA) of Both Knee Joints After Guillain-Barre Syndrome. AB - Heterotopic ossification (HO) is the abnormal development of bone within soft tissue. It is a frequent complication after traumatic as well as atraumatic central nervous system (CNS) insult. It has rarely been found to be associated with Guillain-Barre syndrome (GBS). Only a few cases of HO associated with GBS have been reported so far in medical literature. We present a 30-year-old female patient with severe bilateral knee stiffness following axonal polyneuropathy type of GBS that developed 10 months ago in her immediate post-partum period. She was put on mechanical ventilation for two weeks. She was diagnosed as HO based on clinical and radiological studies. This is an extremely unusual presentation of HO encircling both the knees following GBS without any other well-known risk factors. We have coined a new nomenclature-Heterotopic Ossification Circumferentia Articularis (HOCA)-for this type of presentation. In our patient, various factors such as prolonged ICU stay, mechanical ventilation, hypoxia, and long-standing hypomobility could be attributed to the development of this severe form of HO. PMID- 27004158 TI - Concomitant Granulomatosis with Polyangiitis and C3 Glomerulonephritis Causing Renal Failure. AB - A 75-year-old male with no prior history of vasculitis or renal deficiency presented with a history of 36 hours of anterior epistaxis, one month of worsening shortness of breath, severe anemia requiring transfusion, thrombocytopenia, coagulopathy with INR 4.9, and renal failure requiring hemodialysis. A peripheral blood smear revealed no evidence of microangiopathic hemolytic anemia. We performed an autoimmune workup, which revealed high levels of serum serine protease 3 antibody (C-ANCA), elevated rheumatoid factor, low serum C3, and normal levels of serum C4. We performed a renal biopsy and then performed light microscopy, immunofluorescence, and electron microscopy on the resulting samples. This revealed that approximately half of the sampled glomeruli were globally sclerotic, consistent with severe renal disease. Among the non sclerotic glomeruli, several demonstrated diffuse granular mesangial staining for C3, while other glomeruli had small crescents, consistent with a mixed picture of C3 glomerulonephritis (C3GN) and crescentic glomerulonephritis. The patient responded well to treatment with cyclophosphamide and prednisone, with a resolution of his acute issues, significant improvement in kidney function, and was eventually weaned from routine hemodialysis. In summary, this is a unique case of a patient presenting with features of both granulomatosis with polyangiitis (GPA) and C3GN. PMID- 27004159 TI - Glomerular Function and Structure in Living Donors: Lessons from Single Nephron Studies. AB - One third of the kidney transplants performed in the USA come from living kidney donors. The long-term outcome of healthy individuals who donate kidneys is mostly excellent, although recent studies have suggested that living donation is associated with a small absolute increase in the risk of end stage renal failure. Much of our understanding about the progression of kidney disease comes from experimental models of nephron loss. For this reason, living kidney donation has long been of great interest to renal physiologists. This review will summarize the determinants of glomerular filtration and the physiology that underlies post donation hyperfiltration. We describe the 'remnant kidney' model of kidney disease and the reasons why such progressive kidney disease very rarely ensues in healthy humans following uninephrectomy. We also review some of the methods used to determine glomerular number and size and outline their associations. PMID- 27004161 TI - Induced pluripotent stem cells in cartilage repair. AB - Articular cartilage repair techniques are challenging. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) theoretically provide an unlimited number of specialized cells which could be used in articular cartilage repair. However thus far chondrocytes from iPSCs have been created primarily by viral transfection and with the use of cocultured feeder cells. In addition chondrocytes derived from iPSCs have usually been formed in condensed cell bodies (resembling embryoid bodies) that then require dissolution with consequent substantial loss of cell viability and phenotype. All of these current techniques used to derive chondrocytes from iPSCs are problematic but solutions to these problems are on the horizon. These solutions will make iPSCs a viable alternative for articular cartilage repair in the near future. PMID- 27004162 TI - Evidence base and future research directions in the management of low back pain. AB - Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care. PMID- 27004163 TI - New regulations for medical devices: Rationale, advances and impact on research and patient care. AB - A series of events relating to inferior medical devices has brought about changes in the legal requirements regarding quality control on the part of regulators. Apart from clinical studies, register and routine data will play an essential role in this context. To ensure adequate use of these data, adapted methodologies are required as register data in fact represent a new scientific entity. For the interpretation of register and routine data several limitations of published data should be taken into account. In many cases essential parameters of study cohorts - such as age, comorbidities, the patients' risk profiles or the hospital profile - are not presented. Required data and evaluation procedures differ significantly, for example, between hip and spine implants. A "one fits for all" methodology is quite unlikely to exist and vigorous efforts will be required to develop suitable standards in the next future. The new legislation will affect all high-risk products, besides joint implants also contact lenses, cardiac pacemakers or stents, for example, the new regulations can markedly enhance product quality monitoring. Register data and clinical studies should not be considered as competitors, they complement each other when used responsibly. In the future follow-up studies should increasingly focus on specific questions, while global follow-up investigations regarding product complication rates and surgical methods will increasingly be covered by registers. PMID- 27004164 TI - Entrapment of middle cluneal nerves as an unknown cause of low back pain. AB - Entrapment of middle cluneal nerves induces low back pain and leg symptoms. The middle cluneal nerves can become spontaneously entrapped where this nerve pass under the long posterior sacroiliac ligament. A case of severe low back pain, which was completely treated by release of the middle cluneal nerve, was presented. Entrapment of middle cluneal nerves is possibly underdiagnosed cause of low-back and/or leg symptoms. Spinal surgeons should be aware of this clinical entity and avoid unnecessary spinal surgeries and sacroiliac fusion. This paper is to draw attention by pain clinicians in this unrecognized etiology. PMID- 27004165 TI - Major osteoporotic fragility fractures: Risk factor updates and societal impact. AB - Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence. PMID- 27004166 TI - Injuries in jumpers - are there any patterns? AB - Suicide as a cause of death, affects every health system, and is a particular problem in heavily urbanised states and low and middle income countries (which account for 75% of suicide deaths). The World Health Organisation records that 800000 commit suicide each year, representing 1.4% of annual global deaths, and that suicide was the second leading cause of death in 15-29 year-olds across the world in 2012. In the United Kingdom, jumping from height accounts for 3%-5% of the 140000 suicide attempts annually is similar incidence to the rest of Europe. The Medline and EMBASE were interrogated for studies examining suicide caused by jumping from height. Manual screening of titles and abstracts was used to identify relevant works before data was extracted and systematically reviewed to identify the characteristics of a patient who jumps from height to commit suicide, delineate their patterns of injury and explore techniques that could be used to limit its occurrence. Emergency departments receiving patients who jump from a height need to have an understanding of the potential pathology that is likely to be encountered in order to deliver multidisciplinary, efficient and timely care in order that the impact of this devastating physical, psychological and social problem could modified to the benefit of the patients involved. PMID- 27004167 TI - Outcomes of tenodesis of the long head of the biceps tendon more than three months after rupture. AB - AIM: To demonstrate that long head of the biceps tendon (LHBT) tenodesis is possible more than 3 mo after rupture. METHODS: From September 2009 to January 2012 we performed tenodesis of the LHBT in 11 individuals (average age 56.9 years, range 42 to 73) more than 3 mo after rupture. All patients were evaluated by Disabilites of the Arm Shoulder and Hand (DASH) and Mayo outcome scores at an average follow-up of 19.1 mo. We similarly evaluated 5 patients (average age 58.2 years, range 45 to 64) over the same time treated within 3 mo of rupture with an average follow-up of 22.5 mo. RESULTS: Tenodesis with an interference screw was possible in all patients more than 3 mo after rupture and 90% had good to excellent outcomes but two had recurrent rupture. All of those who had tenodesis less than 3 mo after rupture had good to excellent outcomes and none had recurrent rupture. No statistical difference was found for DASH and Mayo outcome scores between the two groups (P <0.05). CONCLUSION: Tenodesis of LHBT more than 3 mo following rupture had outcomes similar to tenodesis done within 3 mo of rupture but recurrent rupture occurred in 20%. PMID- 27004168 TI - Knee awareness and functionality after simultaneous bilateral vs unilateral total knee arthroplasty. AB - AIM: To investigate knee awareness and functional outcomes in patients treated with simultaneous bilateral vs unilateral total knee arthroplasty (TKA). METHODS: Through a database search, we identified 210 patients who had undergone unilateral TKA (UTKA) and 65 patients who had undergone simultaneous bilateral TKA (SBTKA) at our institution between 2010 and 2012. All TKAs were cemented and cruciate retaining. The mean follow-up period was 3.2 (2 to 4) years. All the patients had symptomatic and debilitating unilateral or bilateral osteoarthritis for which all conservative and non-surgical treatments were failed, thus preoperatively the patients had poor functionality. All patients were asked to complete Forgotten Joint Score (FJS) and Oxford Knee Score (OKS) questionnaires. The patients were matched according to age, gender, year of surgery, Kellgren Lawrence score and pre- and postoperative overall knee alignment. The FJS and OKS questionnaire results of the two groups were then compared. RESULTS: A mixed effects model was used to analyze differences between SBTKA and UTKA. OKS: The mean difference in the OKS between the patients who had undergone SBTKA and those who had undergone UTKA was 1.5, which was not statistically significant (CI = 0.9:4.0, P-value = 0.228). The mean OKS of the SBTKA patients was 37.6 (SD = 9.0), and the mean OKS of the UTKA patients was 36.1 (SD = 9.9). FJS: The mean difference in the FJS between the patients who had undergone SBTKA and those who had undergone UTKA was 2.3, which was not statistically significant (CI = 6.2:10.8, P-value = 0.593). The mean FJS of the SBTKA patients was 59.9 (SD = 27.5), and the mean FJS of the UTKA patients was 57.5 (SD = 28.8). CONCLUSION: SBTKA and UTKA patients exhibited similar joint functionality and knee awareness. Our results support the use of SBTKA in selected patients suffering from clinically symptomatic bilateral osteoarthritis. PMID- 27004169 TI - Isolation and molecular identification of Vibrio spp. by sequencing of 16S rDNA from seafood, meat and meat products in Libya. AB - The genus Vibrio includes several food-borne pathogens that cause a spectrum of clinical conditions including septicemia, cholera and milder forms of gastroenteritis. Several Vibrio spp. are commonly associated with food-borne transmission including Vibrio cholerae, Vibrio parahemolyticus, and Vibrio vulnificus. Microbiological analysis for enumeration and isolation of Vibrio spp. were carried out for a total of 93 samples of seafood, meat and meat products from different geographic localities in Libya (Tripoli, Regdalin, Janzour and Tobruk). Vibrio spp. were detected by conventional cultural and molecular method using PCR and sequencing of 16S rDNA. Out of the 93 cultured samples only 48 (51.6%) yielded colonies on Thiosulfate Citrate Bile Salt agar (TCBS) with culture characteristics of Vibrio spp. More than half (n=27) of processed seafood samples (n=46) yielded colonies on TCBS, while only 44.6 % of samples of meat and meat products showed colonies on TCBS. Among cultured seafood samples, the highest bacterial count was recorded in clam with a count of 3.8 *10(4) CFU?g. Chicken burger samples showed the highest bacterial count with 6.5 *10(4) CFU?g. Molecular analysis of the isolates obtained in this study, showed that 11 samples out of 48 (22.9%) were Vibrio spp. Vibrio parahemolyticus was isolated from camel meat for the first time. This study is an initial step to provide a baseline for future molecular research targeting Vibrio spp. foodborne illnesses. This data will be used to provide information on the magnitude of such pathogens in Libyan seafood, meat and meat products. PMID- 27004170 TI - ORTHOPEDIC COMPLICATIONS IN HIV PATIENTS. AB - The considerable increase of the life expectancy of HIV-infected patients in the age of highly-powerful antiretroviral treatment results in important metabolic and bone-joint changes resulting from a long-lasting viral infection time and from this treatment. The most common orthopaedic complications are bone mineralization changes, osteonecrosis, carpal tunnel syndrome and gleno-humeral adhesive capsulitis, with different clinical presentation features, natural disease progression and therapeutic response compared to the overall population. Literature reports are initial, and the experience of the multidisciplinary service of the University of Sao Paulo's Institute of Orthopaedics and Traumatology enables us a more indepth knowledge about the various pathologies involved and the development of treatment protocols that are appropriate to these diagnoses. PMID- 27004171 TI - ORTHOPEDIC APPROACH TO PECTUS DEFORMITIES: 32 YEARS OF STUDIES. AB - The authors summarize a 32-year experience in the study and in the non-operative approach of pectus carinatum and pectus excavatum. Data of 4,012 patients with pectus deformities were collected from 1977 to January 2009, allowing evaluation on the etiology, pathogenesis and treatment of these deformities. Growth disturbances of anterior chest wall bones and cartilages were detected in imaging studies. Heredity, and biomechanical factors, like respiratory disturbances and scoliosis were noticed in more than 40% of the patients. The method of dynamic remodeling of the thorax - compressive orthoses simultaneously to exercises practice - was indicated in 2453 patients. Concomitant treatment with bending brace was provided in patients with 20 degrees to 52 degrees scoliosis. Of pectus patients with treatment indication, 1717 returned for re-evaluation: 1632 children and adolescents and 85 adults. Good results were seen in 60.6% of children and adolescents and in 27% of adults treated. No scoliosis patient presented curve worsening, and a case of 52 degrees presented an improvement of 20 degrees in the scoliosis with the treatment. Disturbances in the growth of the sternum and costal arches, as well as biomechanical factors related to the pathogenesis of pectus deformities, demonstrate how these deformities are correlated to orthopaedics. Appropriate evaluation of the anterior chest wall and concomitant treatment with bending brace are recommended in the presence of scoliosis. The dynamic remodeling method of the thorax requires a protocol of medical actions for a successful treatment. PMID- 27004172 TI - EPIDEMIOLOGICAL AND RADIOLOGICAL EVALUATION OF FEMORAL SHAFT FRACTURES: STUDY OF 200 CASES. AB - OBJECTIVE: to evaluate epidemiological and radiological characteristics of the femoral shaft fractures, surgically treated from 1990 to 2005 at Hospital de Acidentados - Clinica Santa Isabel - in Goiania, Goias, aiming to contribute to better preventive and therapeutic measures planning to adopt on those fractures. METHODS: 200 patients' files and x-rays with femoral shaft fractures have been retrospectively evaluated. Patients below the age of 10 years were not included because the treatment for this group was conservative. 25 files have been discarded for not supplying all the necessary data to the study. The patients were assessed for sex, age, side of the fracture, bone exposure, mechanisms of trauma, classification of the fractures, associated trauma, time for bone healing and types of surgical devices. Statistic analyses were made by chi-squared, Fisher and Student's-t tests, adopting as a significance level p<0.05. RESULTS: significant results (p < 0.05) were found in: 70% of men, 80% closed fractures and 65% of women above the age of 60. Fractures resulting from simple falls were more frequent in women, above 60 years old, with simpler traces, and the ones caused by projectiles of firearm in men, from 20 to 60 years, with unstable traces. Trampling accidents were prevalent among youngsters between 10 and 19 years old. Car accidents showed all the types of fractures, mostly associated to other traumas, reaching its peak incidence in the age group of 20-30 years. The treatment with Kuntscher Nail resulted in a longer mean consolidation time, as well as fractures with unstable traces (B3,C1,C2,C3). CONCLUSION: we found a bi modal characteristic the femoral shaft fractures, consistently to literature data, where the high energy mechanisms (traffic accidents, high falls and wounds from firearms), have been more frequent in young adults, men, generating unstable traces of fractures, with more serious associated trauma, while the other group with low energy trauma (simple falls), was more frequently seen in elderly female individuals with less unstable fracture traces, without associated trauma. PMID- 27004173 TI - COMPARISON BETWEEN THE RESULTS ACHIEVED IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION WITH TWO KINDS OF AUTOLOGOUS GRAFTS: PATELLAR TENDON VERSUS SEMITENDINOUS AND GRACILIS. AB - OBJECTIVE: this study aims to compare the arthrometric and isokinetic examination results from two types of autologous grafts: the central third of the patellar ligament and a graft formed by the tendons of the semitendinosus and gracilis muscles, within the same rehabilitation protocol, six months after the surgery. METHODS: the results from examinations carried out on 63 patients were analyzed. These patients were divided in two groups: one group of 30 patients who received a patellar tendon graft and another group of 33 patients who received a graft from the tendons of the semitendinosus and gracilis muscles. Both the grafts were attached in the same way, with EndobuttonTM for suspensory fixation to the femur and a bioabsorbable interference screw for fixation in the tibial tunnel. RESULTS: arthrometry 30 did not present any statistical difference between the two study groups. On the other hand, the isokinetic evaluation showed that the patellar tendon group had a larger mean peak torque of flexion and greater extension deficit, while the semitendinosus/gracilis group had a better mean flexion/extension ratio and greater percentage of flexion deficit. There was no statistically significant difference between the groups when measuring peak torque extension. CONCLUSION: therefore, when the patellar tendon was used, there was greater extensor deficit and, when the semitendinosus/gracilis tendons were used, there was greater flexor deficit. PMID- 27004174 TI - SPRENGEL'S DEFORMITY: SURGICAL CORRECTION BY A MODIFIED GREEN PROCEDURE. AB - OBJECTIVE: To evaluate the cosmetic and functional results of patients submitted to surgical correction of Congenital High Scapula (Sprengel's Deformity) using modified Green's Procedure, as well as patients' satisfaction and complications. METHODS: Nine patients submitted to surgical treatment from September 1993 to April 2008 have been assessed. The modification from original technique was: subperiosteal muscle detachment, resection of superomedial scapular portion and fixation of medial portion of scapular spine to contralateral posterior iliac crest instead of skeletal traction, with subcutaneous wire. The mean age was 7 years and 3 months. The mean follow-up time was 3 years and 7 months. RESULTS: The mean improvement in forward elevation was 39o (range 0 to 80o). According to the Cavendish Classification, cosmetic improvement of two degrees was achieved in eight cases, and three degrees in one. All patients were satisfied with results. CONCLUSIONS: Surgical correction of Sprengel's Deformity by a modified Green's procedure with contralateral posterior iliac crest fixation instead of skeletal traction, showed both cosmetic and functional improvements; all patients and/or family members were satisfied with the results, and the complications associated to the surgical technique did not interfere on end results. PMID- 27004175 TI - RELIABILITY AND VALIDITY OF A MODIFIED ISOMETRIC DYNAMOMETER IN THE ASSESSMENT OF MUSCULAR PERFORMANCE IN INDIVIDUALS WITH ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION. AB - OBJECTIVES: The aim of this study was to evaluate the reliability and validity of a modified isometric dynamometer (MID) in performance deficits of the knee extensor and flexor muscles in normal individuals and in those with ACL reconstructions. METHODS: Sixty male subjects were invited to participate of the study, being divided into three groups with 20 subjects each: control group (GC), group of individuals with ACL reconstruction with patellar tendon graft (GTP, and group of individuals with ACL reconstruction with hamstrings graft (GTF). All individuals performed isometric tests in the MID, muscular strength deficits collected were subsequently compared to the tests performed on the Biodex System 3 operating in the isometric and isokinetic mode at speeds of 60 degrees /s and 180o/s. Intraclass ICC correlation calculations were done in order to assess MID reliability, specificity, sensitivity and Kappa's consistency coefficient calculations, respectively, for assessing the MID's validity in detecting muscular deficits and intra- and intergroup comparisons when performing the four strength tests using the ANOVA method. RESULTS: The modified isometric dynamometer (MID) showed excellent reliability and good validity in the assessment of the performance of the knee extensor and flexor muscles groups. In the comparison between groups, the GTP showed significantly greater deficits as compared to the GTF and GC groups. CONCLUSION: Isometric dynamometers connected to mechanotherapy equipments could be an alternative option to collect data concerning performance deficits of the extensor and flexor muscles groups of the knee in subjects with ACL reconstruction. PMID- 27004176 TI - ANALYSIS OF THE REPRODUCIBILITY OF TIBIAL PLATEAU FRACTURES' CLASSIFICATION. AB - OBJECTIVE: To assess the inter-observer agreement of three tibial plateau fracture classifications: Schatzker, AO Group, and Hohl. METHODS: Nine physicians of different levels of expertise (six Orthopaedic Residents - OR - and three Orthopaedic Attendings - OA) classified 50 tibial plateau fractures. RESULTS: There was a low to moderate agreement between OR and OA on the three classification systems. A straight correlation was found between the year of Residence and an increase on the level of agreement on the AO group and Hohl classifications. This was partially seen on the Schatzker classification. Kappa ranged from 0.344 to 0.577, 0.36 to 0.499, and 0.278 to 0.465 for the Hohl, AO group, and Schatzker systems, respectively. CONCLUSION: With a level of 0.1, there was a significant agreement on the three classifications among the physicians. When comparing ORs to OAs, the three studied classifications show low to moderate consistency, with the Hohl classification showing the highest level of agreement between OR. PMID- 27004177 TI - ARTHROSCOPIC TREATMENT OF FEMOROACETABULAR IMPINGEMENT. AB - OBJECTIVE: The purpose of this study is to evaluate the short-term follow-up results of arthroscopic treatment of femoroacetabular impingement. Our hypothesis is that arthroscopic treatment results are favorable. METHODS: Between August 2003 and August 2007, 28 hips had femoroacetabular impingement treated by hip arthroscopy. The mean age was 34 years, with mean follow-up period of 27 months. Clinical results were graded with the modified Harris hip score, which was measured pre- and postoperatively. Patients had also their internal rotation analyzed. These parameters were calculated by using Wilcoxon's t test for analysis of nonparametric paired samples performed. RESULTS: The mean preoperative Harris Hip Score was 54.2, improving to 94.8 postoperatively (p<0,001). The mean increase was 37.5 points. We had 4 good results (15%) and 24 excellent results (85%). Preoperatively, the patients had a mean internal rotation of 17 degrees , and, postoperatively, 36 degrees . The average internal rotation increase was 19 degrees (p<0,001). CONCLUSIONS: The arthroscopic treatment of femoroacetabular impingement presents satisfactory results. PMID- 27004178 TI - PSEUDARTHROSIS OF THE HUMERAL NECK: ANALYSIS OF THE RESULTS WHEN USING THE TECHNIQUE DESCRIBED BY WALCH ET AL. AB - OBJECTIVE: To evaluate bone healing and the patient's outcome after open reduction and internal fixation, when using the technique described by Walch et al, in 1996, which uses conventional intramedullary corticocancellous bone graft and internal fixation with plate and screws added by a tricortical intramedullary bone graft, also autologous. METHODS: From July 1997 to May 2005, 14 patients were treated by this technique, 14 of these diagnosed with pseudoarthrosis of the humeral proximal end. One died at the early postoperative period due to pulmonary thromboembolism; therefore, 13 patients were re-evaluated. RESULTS: The mean follow-up time was 51.4 months (ranging from 12 to 130 months). Four patients evolved with excellent results, four good and five fair results. Therefore, there were 61.5% of satisfactory results according to UCLA functional scale and no poor result. Twelve cases (92%) healed within 3.5 months in average. CONCLUSION: the surgical treatment of the nonunion of the surgical neck of the humerus using this technique showed an effective outcome with 92% of healing; excellent and good results in 61.5% of the cases, as well as satisfaction of all patients with their final results; nonunion resulting from two-part fractures had better results when compared with three-part fractures. PMID- 27004179 TI - OSTEOTOMY OF THE FIRST METATARSAL BASE ON THE TREATMENT OF MODERATE TO SEVERE HALLUX VALGUS RESULTS AFTER MEAN FOLLOW-UP TIME OF EIGHT YEARS. AB - OBJECTIVE: To assess the result of the treatment of moderate to severe hallux valgus with osteotomy of the first metatarsal base associated to distal release of soft parts and medial capsuloplasty. METHODS: 13 patients were assessed (15 feet) submitted to surgical treatment of hallux valgus moderate to severe. The mean follow-up time was 102 months; there were 12 female and 1 male patients, with mean age at the time of surgery of 49 years. The patients enrolled were interviewed according to the questionnaire developed by our service, clinically examined according to the AOFAS scale and submitted to X-ray tests for comparing the results with baseline images. RESULTS: The mean score of the AOFAS scale obtained at the final assessment was 82 points. Nine of the 15 feet (60%) showed some late complications, with four (27%) varus deformities, three (20%) recurrences; two patients (13%) presenting with pain complaints with no associated deformity. In the hallux metatarsophalangeal joint, movement loss was 41 degrees (57%); dorsiflexion movement was mostly affected, with a mean loss of 37 degrees (60%). The range of motion on the contralateral intact side served as control group. Arthrosis progression was seen on the final X-ray evaluation. In all cases, shortening and lifting of the first metatarsal were noticed; however, we couldn't correlate the shortening and lifting with metatarsalgia, plant callosity or lower scoring on the AOFAS scale at the final evaluation. CONCLUSIONS: The osteotomy technique by the basis and with distal realignment of soft parts employed in the treatment of moderate to severe hallux valgus showed a high rate of late complications. Due to the high number of complications, we believe that adopting this technique for correcting hallux valgus deformities should be carefully considered. PMID- 27004180 TI - DISSEMINATED REFRACTARY TUBERCULOSIS WITH BICEPS TENDON INVOLVEMENT IN AN IMMUNOCOMPETENT PATIENT. AB - OBJECTIVE: The authors report a rare case of disseminated tuberculosis which had compromised the long head of biceps tendon and shoulder joint, during standard drug therapy. METHODS: On a first sight, the accurate diagnosis wasn't accomplished and the patient had been treated with physiotherapy for rotator cuff tear. However, the patient presented with a fast growing mass in anterior region of the proximal third of the arm, complaining of pain increase. Aspirative punction of the mass revealed a yellow fluid and the laboratorial analysis confirmed infection by M. Tuberculosis. The patient was treated with surgical debridement and his drug therapy was changed. RESULTS: Resolution of infectious status and complete shoulder function restoration was succeeded. CONCLUSION: Due to its high prevalence in Brazil, tuberculosis must always be considered as a possible cause of inflammatory joint disease, even in immunocompetent patients. PMID- 27004181 TI - RAPID MANUFACTURING SYSTEM OF ORTHOPEDIC IMPLANTS. AB - This study, aimed the development of a methodology for rapid manufacture of orthopedic implants simultaneously with the surgical intervention, considering two potential applications in the fields of orthopedics: the manufacture of anatomically adapted implants and implants for bone loss replacement. This work innovation consists on the capitation of the in situ geometry of the implant by direct capture of the shape using an elastomeric material (polyvinylsiloxane) which allows fine detail and great accuracy of the geometry. After scanning the elastomeric specimen, the implant is obtained by machining using a CNC milling machine programmed with a dedicated CAD/CAM system. After sterilization, the implant is able to be placed on the patient. The concept was developed using low cost technology and commercially available. The system has been tested in an in vivo hip arthroplasty performed on a sheep. The time increase of surgery was 80 minutes being 40 minutes the time of implant manufacturing. The system developed has been tested and the goals defined of the study achieved enabling the rapid manufacture of an implant in a time period compatible with the surgery time. PMID- 27004182 TI - Scientific Output. PMID- 27004183 TI - OSTEOSYNTHESIS WITH INTRAMEDULLARY NAILS IN CHILDREN. AB - The authors present a comprehensive review of the literature emphasizing the use of flexible intramedullary nails in the treatment of fractures in children, focusing the treatment of femoral shaft and forearm fractures and emphasizing the importance of the non-surgical approach. Children's age and weight threshold are not well defined for the use of the method. The removal of implants is a controversial matter in the literature, with a trend towards keeping the implants. PMID- 27004184 TI - BENIGN BONE TUMORS AND TUMOR-LIKE BONE LESIONS: TREATMENT UPDATE AND NEW TRENDS. AB - The treatment of benign bone tumors (BBT) and tumor-like bone lesions (TBL) has observed the introduction of new drugs, such as intravenous bisphosphonates, which have ossified bone lesions caused by fibrous dysplasia. Aneurismal bone cyst has been treated with sclerosing agents by percutaneous injection, yielding good results. Adjuvants allow joint salvage, maintenance of movements and function, with low rates of recurrence. Among them, the most used ones are bone cement (PMMA), phenol, nitrogen-based cryotherapy, hydrogen peroxide, ethanol and radiotherapy. New methods of treatment include thermal ablation with radiofrequency and laser, mainly utilized for treating osteoid osteoma. Arthroscopy allows resection of benign intra-joint lesions and assists the surgery of subchondral tumors. A great advance is the utilization of synthetic bone substitutes, which are a mixture of osteoinductive growth factors and osteoconductive ceramics, and have presented comparable results to autogenous bone grafts. There is a recent trend for closed treatments, with percutaneous injection of demineralized bone matrix (DBM) and calcium sulfate. Autogenous cancellous bone graft remains as the gold standard. Vascularized fibula graft, on the other hand, incorporates faster in the treatment of large destructive lesions. Also, allogenic cortical support allows structural augmentation for aggressive tumors. Freeze-dried allografts are used to fill contained defects and as expanders of autografts. Joint endoprosthesis may be used in large destructive lesions of the distal femur, hip and shoulder. PMID- 27004185 TI - TREATMENT OF TRAUMATIC GLENOHUMERAL DISLOCATION: A CROSS-SECTIONAL STUDY. AB - OBJECTIVE: The aim of the present study was to investigate Brazilian orthopedists' opinions regarding the main aspects of the treatment of glenohumeral traumatic dislocation and compare these to literature's current concepts. METHODS: Two hundred questionnaires containing 13 items were randomly distributed to orthopedists who were attending a Brazilian orthopedics congress; 158 were filled, in correctly and were considered in this study. RESULTS: The preferred maneuver was traction-countertraction (60.8%). Among the respondents, 68.4% stated that glenohumeral dislocation reduction was achieved in the first attempt in 90% of the cases. The first attempt of reduction occurred mainly in the Emergency room (96.5%). Seventy-nine individuals (50%) reported that they do not use any analgesic prior to reduction. The majority of the participants immobilize their patients after the reduction (98.1%). 75.4% of them keep their patients immobilized from 2 to 3 weeks. CONCLUSION: Generally, Brazilian orthopaedists perform tractioncountertraction maneuvers, achieving reduction in the first attempt in more than 90% of the cases in the Emergency room. No previous analgesic agent is used prior to reduction. Immobilization of the patient is made with a Velpeau dressing or a sling for 2 to 3 weeks. PMID- 27004186 TI - THE ROLE OF FIBRIN GLUE AND SUTURE ON THE FIXATION OF ULTRA FROZEN PRESERVED MENISCUS TRANSPLANTATION IN RABBITS. AB - OBJECTIVE: To evaluate the ability of fibrin adhesive in promoting the meniscus fixation within two, four and eight weeks compared to the conventional soft tissue suture technique. MATERIALS AND METHODS: 36 right medial menisci of rabbits preserved at negative 73 degrees Celsius for 30 days were transplanted to animals of the same sample and fixed with soft-tissue suture or fibrin glue. After 2, 4 or 8 weeks, the appearance of the menisci and the quality of fixation were macroscopically checked and evaluated by a scoring system. The findings were subjected to the statistical study of variance analysis (p <= 0.05%). RESULTS: The deep-frozen meniscus preservation maintained the integrity of the meniscus transplant, and, macroscopically, there was no significant reduction of the length of the meniscus in all post-transplant periods (p = 0.015). The menisci fixed with fibrin showed slight changes in color and surface roughness. There were no signs of rejection or infection in both groups. Suture fixation scoring was superior (p = 0.015) in all periods (80% of total fixation) as compared to the setting promoted by fibrin (20% of total fixation). CONCLUSION: The homologous transplantation of the meniscus of rabbits experienced various degrees of integration to the knee according to the fixation method; the surgical soft tissues suturing technique was shown to be superior in the evaluation of scores compared to the fixation with fibrin adhesive. PMID- 27004187 TI - CONTRIBUTION TO THE ANATOMICAL STUDY OF THE CORTICOPERIOSTEAL FLAP OF THE MEDIAL FEMORAL CONDYLE. AB - OBJECTIVE: to perform the anatomical study, in cadavers, of the corticoperiosteal flap of the medial femoral condyle, based on the medial genicular artery, evaluating challenges in dissection and the topographic patterns. MATERIALS AND METHODS: fifteen limbs from eight cadavers were studied, ages ranging from 19 to 74 years old. They were placed at supine position, and a longitudinal incision on the medial face of the lower part of the thigh was performed, exposing medial vastus and sartorius muscles, with descendent genicular vessels being also exposed. The distance between the descendent genicular artery and the medial articular line of the knee, the diameter of the vessel, the length of the pedicle, and the presence of the fasciocutaneous branch and its location were analyzed. RESULTS: the distance between the origin of the descendent genicular artery and the medial articular line of the knee ranged from 11.2cm to 14.5cm, with an average of 12.63cm. The mean artery diameter was 2.5mm (from 2.25mm to 2.75mm). The distance between the descendent genicular artery and the fasciocutaneous branch ranged from 1.0 to 1.5cm. The mean length of the vascular pedicle was 7.01cm, ranging from 5.6cm to 8.6cm. CONCLUSION: the corticoperiosteal flap of the medial femoral condyle of the knee is easy to dissect, presents a constant vascular pedicle, with average length of 7.0cm and diameter of 2.5mm, enabling it to be indicated for microsurgical transplants. PMID- 27004188 TI - THORACOLUMBAR BURST FRACTURES: CORRELATION BETWEEN KYPHOSIS AND FUNCTION POST NON OPERATIVE TREATMENT. AB - OBJECTIVE: To assess the correlation between kyphosis and post-traumatic symptoms in patients undergoing conservative treatment for thoracolumbar burst fractures. METHODS: A retrospective study was carried out with 36 patients meeting the inclusion criteria for this kind of fracture classified as Denis and Magerl's subtype A3 and treated with anti-gravitational casting or TLSO. The mean age of patients was 50.83 years, ranging from 13 to 83 years, being 20 male and 16 female subjects. The treatment outcome was evaluated based on the SF-36 questionnaire, on Denis scores for pain and work and Frankel clinical and neurological scale. The quantification of pain was based on the visual analogue scale for pain. The measurement of the residual kyphosis was obtained by the Cobb method at admission and at the end of the follow-up. RESULTS: A weak positive correlation (r = 0.563; p > 0.001) was found between residual kyphosis and pain score (EVA). No correlation was found between final kyphosis and SF-36 and Denis scores (p > 0.05). CONCLUSION: There is no evident correlation between residual kyphosis, functional outcome and patients' symptoms. PMID- 27004189 TI - BIOMECHANICAL EVALUATION OF THE INFLUENCE OF CERVICAL SCREWS TAPPING AND DESIGN. AB - OBJECTIVE: To assess if the screw design (self-drilling/self-tapping) and the pilot hole tapping could affect the insertion torque and screw pullout strength of the screw used in anterior fixation of the cervical spine. METHODS: Forty self tapping screws and 20 self-drilling screws were inserted into 10 models of artificial bone and 10 cervical vertebrae of sheep. The studied parameters were the insertion torque and pullout strength. The following groups were created: Group I-self-tapping screw insertion after pilot hole drilling and tapping; Group II-self-tapping screw insertion after pilot hole drilling without tapping; Group III-self-drilling screw insertion without drilling and tapping. In Groups I and II, the pilot hole had 14.0 mm in depth and was made with a 3mmn drill, while tapping was made with a 4mm tap. The insertion torque was measured and the pullout test was performed. The comparison between groups was made considering the mean insertion torque and the maximum mean pullout strength with the variance analysis (ANOVA; p<= 0.05). RESULTS: Previous drilling and tapping of pilot hole significantly decreased the insertion torque and the pullout strength. CONCLUSION: The insertion torque and pullout strength of self-drilling screws were significantly higher when compared to self-tapping screws inserted after pilot hole tapping. PMID- 27004190 TI - INTEGRITY OF THE SUBSCAPULARIS TENDON AFTER OPEN SURGERY FOR THE TREATMENT OF ANTERIOR SHOULDER INSTABILITY: A CLINICAL AND RADIOLOGICAL EVALUATION. AB - OBJECTIVE: To evaluate the integrity of the subscapularis tendon by strength, function and magnetic resonance imaging after deltopectoralis access for anterior shoulder instability. METHODS: 20 patients with anterior shoulder instability have been evaluated. Minimum follow-up was 12 months, with a mean of 40 months. Only male patients were included, with a mean of age of 29 years (20 - 42 years). The patients have been submitted to physical examinations of mobility, muscular strength, Belly Test and Gerber Test. The isokinetic strength in internal and external rotation, in angular speeds of 60(0)/s and 180(0)/s, for both shoulders was measured using a dynamometer. In 15 patients magnetic resonance imaging (MRI) was carried out on both shoulders for evaluating the thickness, cross-sectional area and atrophy of the subscapularis muscle. RESULTS: A significant difference was found between torque peaks at the speed of 60(0)/s for internal (p=0.036) and external (p=0.008) rotation. However, at 180(0)/s the opposite happens (internal rotation: p=0.133; external rotation: p=0.393). Subscapularis muscle thickness and area are significantly smaller than the normal side, with a deficit of 19% and 23%, respectively. According to Rowe and UCLA scores, we find excellent and good results for the majority of patients, with a mean of 88 and 31.6 points, respectively. CONCLUSION: Despite of the good functional results, open surgery can limit strength and reduce the thickness and the cross-sectional area of subscapularis muscle. However, the best results were found in the patients who had the dominant side operated. PMID- 27004191 TI - ANALYSIS OF THE SEGMENTAL IMPACTION OF FEMORAL HEAD FOLLOWING AN ACETABULAR FRACTURE SURGICALLY MANAGED. AB - OBJECTIVE: Correlate the postoperative radiographic evaluation with variables accompanying acetabular fractures in order to determine the predictive factors for segmental impaction of femoral head. METHODS: Retrospective analysis of medial files of patients submitted to open reduction surgery with internal acetabular fixation. Within approximately 35 years, 596 patients were treated for acetabular fractures; 267 were followed up for at least two years. The others were excluded either because their follow up was shorter than the minimum time, or as a result of the lack of sufficient data reported on files, or because they had been submitted to non-surgical treatment. The patients were followed up by one of three surgeons of the group using the Merle d'Aubigne and Postel clinical scales as well as radiological studies. RESULTS: Only tow studied variables-age and amount of postoperative reductionshowed statistically significant correlation with femoral head impaction. CONCLUSIONS: The quality of reduction-anatomical or with up to 2mm residual deviation-presents a good radiographic evolution, reducing the potential for segmental impaction of the femoral head, a statistically significant finding. PMID- 27004192 TI - LONG-TERM RESULTS OF BODY AND NECK TALUS FRACTURES. AB - OBJECTIVES: Talar neck and body fractures are unusual fractures. The purpose of this study is to determine the prevalence of long term results. MATERIAL AND METHODS: A retrospective analysis was carried out including 11 patients that underwent surgical treatment for body or neck talus fractures between January 1997 and December 2005. Final follow-up examination included a clinical evaluation (AOFAS score) and standard radiographs. RESULTS: The mean follow-up time was 58.5 months. The prevalence of associated fractures was 60% (6/10). Overall AOFAS score averaged 72 [19-100]. Avascular necrosis and post-traumatic arthritis were present in half of the patients. Quality of surgical reduction, body fractures and absence of degenerative changes were correlated with better functional results. Neck fractures, osteonecrosis and posttraumatic arthritis led to inferior results. CONCLUSION: There is a great potential for long term functional impairment due to posttraumatic arthritis and chronic pain in this kind of fracture. Anatomic surgical reduction is the best chance to avoid them but it is not infallible. The avascular necrosis rate correlates with initial fracture displacement, but its occurrence in each specific case is unpredictable. PMID- 27004193 TI - SYNOVIAL GIANT CELL TUMOR OF THE KNEE. AB - Synovial giant cell tumor is a benign neoplasm, rarely reported in the form of malignant metastasis. Synovial giant cell tumor most frequently occurs on the hand, and, most uncommon, on the ankle and knee. In the present study, the authors describe a rare case of synovial giant cell tumor on the knee as well as the treatment approach. Arthroscopy has been shown, in this case, to be the optimal method for treating this kind of lesion, once it allowed a less aggressive approach, while providing good visualization of all compartments of knee joint and full tumor resection. PMID- 27004194 TI - DARTHROSCOPIC DOUBLE- BUNDLE RECONSTRUCTION OF ANTERIOR CRUCIATE LIGAMENT USING HAMSTRING TENDON GRAFTS - FIXATION WITH TWO INTERFERENCE SCREWS. AB - Surgical procedures for double-bundle reconstruction of anterior cruciate ligament, which currently use semitendinous and gracilis tendon grafts, have been described in the last decade. Most of the techniques utilize twice the hardware used in single-bundle reconstructions. We report an original anterior cruciate ligament double-bundle reconstruction technique using semitendinous and gracilis tendon grafts, maintaining their tibial bone insertions with two tibial and two femoral tunnels. A simplified and precise outside-in femoral drilling technique is utilized, and the graft fixation is made utilizing only two interference screws. PMID- 27004195 TI - The role of the RBO: 70 years of support to the Brazilian orthopedic surgeon n. PMID- 27004196 TI - Fetal heart rate monitoring: from Doppler to computerized analysis. AB - The monitoring of fetal heart rate (FHR) status is an important method to check well-being of the baby during labor. Since the electronic FHR monitoring was introduced 40 years ago, it has been expected to be an innovative screening test to detect fetuses who are becoming hypoxic and who may benefit from cesarean delivery or operative vaginal delivery. However, several randomized controlled trials have failed to prove that electronic FHR monitoring had any benefit of reducing the perinatal mortality and morbidity. Also it is now clear that the FHR monitoring had high intra- and interobserver disagreements and increased the rate of cesarean delivery. Despite such limitations, the FHR monitoring is still one of the most important obstetric procedures in clinical practice, and the cardiotocogram is the most-used equipment. To supplement cardiotocogram, new methods of computerized FHR analysis and electrocardiogram have been developed, and several clinical researches have been currently performed. Computerized equipment makes us to analyze beat-to-beat variability and short term heart rate patterns. Furthermore, researches about multiparameters of FHR variability will be ongoing. PMID- 27004197 TI - External cephalic version experiences in Korea. AB - OBJECTIVE: The aim of this study was to evaluate obstetric outcomes of external cephalic version (ECV) performed at or near term. METHODS: Single pregnant woman with breech presentation at or near term (n=145), who experienced ECV by one obstetrician from November 2009 to July 2014 in our institution were included in the study. Maternal baseline characteristic and fetal ultrasonographic variables were checked before the procedure. After ECV, the delivery outcomes of the women were gathered. Variables affecting the success or failure of ECV were evaluated. RESULTS: Success rate of ECV was 71.0% (n=103). Four variables (parity, amniotic fluid index, fetal spine position and rotational direction) were observed to be in correlation with success or failure of ECV. In contactable 83 individuals experienced successful ECV, cesarean delivery rates were 18.1%, 28.9%, and 5.3% in total, nulliparas, and multiparas, respectively. CONCLUSION: Based on the results, ECV is proposed to be safe for both mother and her fetus. In addition, it is a valuable procedure that increases probability of vaginal delivery for women with breech presentation. PMID- 27004198 TI - Simple mathematical formulae for estimation of median values of fetal biometry at each gestational age. AB - OBJECTIVE: The aim of this study was to propose simple mathematical formulae to estimate median values of fetal biometry including biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) at each gestational age (GA) easily without looking up the previously established reference values. METHODS: Simple mathematical formulae to estimate median values of fetal biometric values at each gestational week were inferred. To validate these formulae, three different linear equations were derived from previously reported reference values of median BPD, AC and FL using regression analysis at each gestational week. Finally, calculated data through the inferred formula were compared to retrospectively collected data (observed data). RESULTS: The equation revealing the relationship between BPD and GA was: median BPD (cm)=GA (wk)/4. Using this simple mathematical formula, the absolute percentage error between observed data and calculated data ranged from 0.12% to 7.50%. The equation between AC and GA was: median AC (cm)=GA (wk)-5. Through this formula, the absolute percentage error was analyzed same as above and it ranged from 0.30% to 4.76%. Lastly the derived formula between FL and GA was: median FL (cm)=GA (wk)/5 and the absolute percentage error ranged from 4.52% to 16.75%. CONCLUSION: The three simple formulae suggested in our study showed a significantly easy way to estimate the median values of fetal biometry at each gestational week with good reliability. PMID- 27004199 TI - Preoperative and postoperative serum C-reactive protein levels to predict the outcome of ultrasound-indicated cerclage. AB - OBJECTIVE: To assess the role of preoperative and postoperative serum C-reactive protein (CRP) level on the prediction of pregnancy outcomes following ultrasound indicated cerclage (UIC). METHODS: We retrospectively reviewed the medical records 44 women who underwent UIC between January 2011 and December 2011. UIC was performed between 14 and 24 weeks of gestation in women with short cervix. We divided UIC patients into two groups according to the gestational age at delivery (34 weeks) and compared the two groups. Group A was defined as patients who delivered >=34 weeks of gestation, and group B as patients delivered <34 weeks. Correlation and receiver-operating characteristic curves were also analyzed for the prediction of preterm birth after UIC. RESULTS: Thirty women delivered >=34 weeks (group A) and 14 women delivered <34 weeks (group B). Pre- and post cerclage CRP were significantly lower in group A (pre-cerclage CRP, 1.1+/-1.0 vs. 11.4+/-6.2 mg/dL, P<0.001; post-cerclage CRP, 0.6+/-0.5 vs. 7.4+/-7.2 mg/dL, P<0.001). The mean gestational age at delivery in group A was 37.7+/-1.8 weeks and that in group B was 26.9+/-4.3 weeks (P<0.001). There were significant negative correlations between pre- and post-cerclage CRP and latency from UIC to delivery (r=-0.82, P<0.001; r=-0.70, P<0.001, respectively). CONCLUSION: Both pre and post-cerclage CRP were useful in predicting the preterm birth following UIC. PMID- 27004200 TI - Safety of cesarean delivery through placental incision in patients with anterior placenta previa. AB - OBJECTIVE: To demonstrate the safety of fetal delivery through placental incision in a placenta previa pregnancy. METHODS: We examined the medical records of 80 women with singleton pregnancy diagnosed with placenta previa who underwent cesarean section between May 2010 and May 2015 at the Department of Obstetrics and Gynecology, Chungbuk National University Hospital. Among the women with placenta previa, those who did not have the placenta in the uterine incision site gave birth via conventional uterine incision, while those with anterior placenta previa or had placenta attached to the uterine incision site gave birth via uterine incision plus placental incision. We compared the postoperative hemoglobin level and duration of hospital stay for the mother and newborn of the two groups. RESULTS: There was no difference between the placental incision group and non-incision group in terms of preoperative and postoperative hemoglobin change, the amount of blood transfusions required by the mother, newborns with 1 min or 5-min Apgar scores below 7 points or showing signs of acidosis on umbilical cord blood gas analysis result of pH below 7.20. Moreover, neonatal hemoglobin levels did not differ between the two groups. CONCLUSION: Fetal delivery through placental incision during cesarean section for placenta previa pregnancy does not negatively influence the prognosis of the mother or the newborn, and therefore, is considered a safe surgical technique. PMID- 27004201 TI - Folic acid alone or multivitamin containing folic acid intake during pregnancy and the risk of gestational hypertension and preeclampsia through meta-analyses. AB - OBJECTIVE: The objective of this study was to assess the effect of folic acid and multivitamin use during pregnancy on the risk of developing of hypertensive disorder of pregnancy. METHODS: Two reviewers independently determined all prospective cohort study, retrospective cohort study, large population based cohort study, retrospective secondary analysis, and double blinded, placebo controlled, randomized clinical trial published using PubMed Medline database, KERIS (Korea Education and Research Information Service), Scopus, and the Cochrane Central Register of controlled trials comparing before conception throughout pregnancy intake oral multivitamin containing folic acid or folic acid alone. Meta-analyses were estimated with odds ratios and 95% confidence intervals (CIs) using random effect analysis according to heterogeneity of studies. RESULTS: Data from six effect sizes from six studies involving 201,661 patients were enrolled. These meta-analyses showed multivitamin containing folic acid or folic acid alone was not significantly effective in reducing gestational hypertension or preeclampsia incidence (odds ratio, 0.91; 95% CI, 0.81 to 1.03) than the placebo. And the difference of effective sizes of preeclampsia and gestational hypertension according to two dependent variables, multivitamin and folic acid were not significant, respectively (point estimate, 0.66; 95% CI, 0.46 to 0.96). CONCLUSION: These meta-analyses demonstrate multivitamin containing folic acid or folic acid alone was not significantly effective in reducing gestational hypertension or preeclampsia incidence. PMID- 27004202 TI - Prognostic factors in neuroendocrine cervical carcinoma. AB - OBJECTIVE: To evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine cervical carcinoma (NECC). METHODS: The records of 61 patients with NECC diagnosed between 2000 and 2014 at Seoul National University Hospital and the National Cancer Center were retrospectively reviewed. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: Of the 61 patients, 67.2% were diagnosed at early stage (I to IIA) with a median age of 49 years. Of those, 78% underwent surgery and 75.6% received postoperative adjuvant treatment. For patients diagnosed at advanced stage, 60.0% received chemotherapy only and 25.0% received concurrent chemoradiation therapy. In the univariate analysis, advanced stage (77 vs. 40 months, P=0.013), tumor size >=2 cm (133 vs. 47 months, P=0.002) and mixed tumor (101 vs. 34 months, P=0.004) were shown to be poor prognostic factors. In the multivariate analysis, tumor stage, tumor size and tumor homology were shown to be independent prognostic factors for overall survival. Of the total, 39.3% of the patients experienced recurrence, and 54.1% of the patients had metastasis. Of the patients diagnosed at early stage, 51.2% experienced recurrence. CONCLUSION: Tumor stage, tumor size and tumor homology were found to be independent prognostic factors in patients with NECC. Even in patients diagnosed at early stage, recurrence and distant metastasis were frequently observed. PMID- 27004203 TI - Increased expression of nuclear factor kappa-B p65 subunit in adenomyosis. AB - OBJECTIVE: Nuclear factor kappa-B (NF-kappaB) is a critical proinflammatory regulator that has been suggested to play a pivotal role in the pathogenesis and pathophysiology of endometriosis. In the present study, we aimed to evaluate whether the expression of NF-kappaB p65 subunit is increased in the eutopic endometrium and/or in the adenomyosis nodule of women with adenomyosis. METHODS: Thirty-three women with histologically confirmed adenomyosis after laparoscopic or transabdominal hysterectomy were recruited. Women with carcinoma in situ of uterine cervix without evidence of adenomyosis or endometriosis (n=32) served as controls. Formalin-fixed, paraffin-embedded archival tissues were sectioned and immunostained utilizing a monoclonal anti-human NF-kappaB p65 subunit antibody, and the immunoreactivity of NF-kappaB p65 subunit was compared between women with and without adenomyosis. RESULTS: The immunoreactivities of both the nuclear and the cytoplasmic NF-kappaB p65 subunit were significantly increased in the stromal cells in the eutopic endometrium as well as in the adenomyosis nodule of women with adenomyosis compared with controls, respectively. The nuclear expression of NF-kappaB p65 subunit was significantly higher in the glandular cells in the eutopic endometrium as well as the adenomyosis nodule of women with adenomyosis compared with controls, respectively. CONCLUSION: The expression of NF-kappaB p65 is increased in the eutopic endometrium and adenomyosis nodule of women with adenomyosis, which strongly suggest that NF-kappaB plays a critical role in the pathogenesis and/or pathophysiology of adenomyosis. PMID- 27004204 TI - Clinical and microbiologic characteristics of vulvovaginitis in Korean prepubertal girls, 2009-2014: a single center experience. AB - OBJECTIVE: To update information on the clinical and microbiologic characteristics of pediatric vulvovaginitis in Korean prepubertal girls. METHODS: A total of 120 girls (aged 0 to 9 years) with culture-confirmed pediatric vulvovaginitis, diagnosed between 2009 and 2014, were enrolled in the study. The epidemiologic and microbiologic characteristics, and clinical outcomes were assessed. Patients with sexual precocity, as well as those who were referred for suspected sexual abuse, were excluded. RESULTS: Girls aged 4 to 6 years were at the highest risk of pediatric vulvovaginitis. Seasonal distribution indicated obvious peaks in summer and winter. Of the 120 subjects, specific pathogens were identified in the genital specimens in only 20 cases (16.7%). Streptococcus pyogenes (n=12, 60%) was the leading cause of specific vulvovaginitis. Haemophilus influenzae was isolated in one patient. No cases presented with enteric pathogens, such as Shigella or Yersinia. A history of recent upper respiratory tract infection, swimming, and bubble bath use was reported in 37.5%, 15.8%, and 10.0% of patients, respectively. Recent upper respiratory tract infection was not significantly correlated with the detection of respiratory pathogens in genital specimens (P>0.05). Of 104 patients who underwent perineal hygienic care, 80 (76.9%) showed improvement of symptoms without antibiotic treatment. Furthermore, the efficacy of hygienic care was not significantly different between patients with or without specific pathogens (P>0.05). CONCLUSION: Specific pathogens were only found in 16.7% of pediatric vulvovaginitis cases. Our results indicate an excellent outcome with hygienic care, irrespective of the presence of specific pathogens. PMID- 27004205 TI - Risk factors for urinary retention after vaginal hysterectomy for pelvic organ prolapse. AB - OBJECTIVE: To evaluate the risk factors for postoperative urinary retention in women who underwent vaginal hysterectomy for symptomatic pelvic organ prolapse. METHODS: The medical records of 221 women who underwent vaginal hysterectomy with anterior and posterior colporrhapy were reviewed. Urinary retention after catheter removal was defined as the presence of at least one of the following three conditions: 1) failure of first voiding trial necessitating catheterization, 2) first residual urine volume after self-voiding >=150 mL, and 3) Foley catheter re-insertion. RESULTS: Urinary retention occurred in 60 women (27.1%). Multivariate and receiver operating characteristic curve analysis revealed that age (>63 years) and early postoperative day of catheter removal (day 1) was independent predictor for postoperative urinary retention. The incidence of urinary retention was significantly higher in women who removed indwelling catheter at day 1 (35.2%) than those at day 2 (12.0%, P=0.024), or day 3 (21.3%, P=0.044), but was similar to those at day 4 (25.0%, P=0.420). In women <=63 years, urinary retention rate was not associated with the time of catheter removal after surgery; however, in women >63 years, the rate was significantly higher in day 1 removal group than day 2 to 4 removal group. CONCLUSION: Age and postoperative day of catheter removal appear to be associated with postoperative urinary retention in women undergoing vaginal hysterectomy for pelvic organ prolapse. Keeping urinary catheter in situ at least for one day after vaginal prolapse surgery could be recommended, especially, in women older than 63 years. PMID- 27004206 TI - A live birth after spontaneous complete chorioamniotic membrane separation associated with uterine scar. AB - Spontaneous complete chorioamniotic membrane separation (CMS) without invasive fetal procedure is extremely rare and associated with adverse perinatal outcomes. A woman with complete CMS which was detected at the 21 weeks' gestation. She did not take any fetal invasive procedures before the diagnosis. At 27 weeks' gestation, an emergency Caesarean section was performed because of fetal distress. The defect of the uterine muscle was detected on the fundus. The baby has grown well without any morbidity. This is the first reported case of complete CMS relative to uterine scar. And we suggest that the pregnancy can be maintained successfully if there is no fetal abnormality when complete CMS is detected on ultrasound. PMID- 27004207 TI - Hypertriglyceridemia-induced acute pancreatitis in pregnancy causing maternal death. AB - Acute pancreatitis in pregnancy is rare and occurs in approximately 3 in 10,000 pregnancies. It rarely complicates pregnancy, and can occur during any trimester, however over half (52%) of cases occur during the third trimester and during the post-partum period. Gallstones are the most common cause of acute pancreatitis. On the other hand, acute pancreatitis caused by hypertriglyceridemia due to increase of estrogen during the gestational period is very unusual, but complication carries a higher risk of morbidity and mortality for both the mother and the fetus. We experienced a case of pregnant woman who died of acute exacerbation of hypertriglyceridemia-induced acute pancreatitis at 23 weeks of gestation. We report on progress and management of this case along with literature reviews. PMID- 27004208 TI - Endometrial adenocarcinoma in a 13-year-old girl. AB - Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature. PMID- 27004209 TI - Genetic analysis of ovarian microcystic stromal tumor. AB - Microcystic stromal tumor (MCST) of the ovary is a rare subtype of ovarian tumor first described in 2009. Although high nuclear expression of beta-catenin and beta-catenin gene (CTNNB1) mutation are related with ovarian MCST, the origin and genetic background of ovarian MCST remain unclear. In this study, two cases of ovarian MCST are presented. Microscopically, the tumors showed a microcystic pattern and regions with lobulated cellular masses with intervening hyalinized, fibrous stroma. Tumor cells of both cases were stained with CD10, vimentin, and Wilms tumor 1. Genetic analysis was performed and beta-catenin gene (CTNNB1) mutation in exon 3 was detected in both cases. This is the first report in regards of detecting CTNNB1 mutation in ovarian MCST through the use of pyrosequencing (a novel sequencing technique). PMID- 27004210 TI - Pelvic artery embolization in the management of pelvic arterial bleeding following midurethral sling surgery for stress urinary incontinence. AB - The transobturator tape (TOT) method is the recent minimally invasive midurethral sling surgery. The TOT method was invented to reduce complication rate of surgical technique for female stress urinary incontinence. Pelvic bleeding following TOT procedure, although extremely rare, could be occurred. We presented three cases which treat pelvic arterial bleeding after midurethral sling (TOT and tension-free vaginal tape Secur) surgery via pelvic artery embolization. Therefore we report our cases with brief review of the literature. PMID- 27004211 TI - Glypican-1 in exosomes as biomarker for early detection of pancreatic cancer. AB - On June 24, 2015 Nature published an article entitle "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer'', which demonstrates that exosomes positives for the proteoglycan glypican-1 (GPC1) are expressed in serum of patients with pancreatic cancer since very early stages but not in benign pancreatic disease. Additionally, these GPC1(+) circulating exosomes correlate with tumor burden and could be used as prognostic biomarker in pre and post surgical patients. The study is pioneer since GPC1 biomarker in exosomes offers better sensitivity and specificity than any other under evaluation or used in clinical practice. However, methodology for exosomes isolation still remains at investigational phase. Further studies are need to translate this technology to a practicable clinical method. Further research is also required to validate this biomarker in larger prospective cohort including more cases of premalignant lesions and then replicated results could possible guide changes in clinical practice. PMID- 27004212 TI - Visnagin-a new protectant against doxorubicin cardiotoxicity? Inhibition of mitochondrial malate dehydrogenase 2 (MDH2) and beyond. PMID- 27004214 TI - Getting familiar with the forthcoming eighth edition of TNM classification of lung cancer: from the T to N and M descriptors. PMID- 27004213 TI - Significance of IASLC/ATS/ERS classification for early-stage lung adenocarcinoma patients in predicting benefit from adjuvant chemotherapy. PMID- 27004215 TI - Intraoperative brain cancer detection with Raman spectroscopy in humans. PMID- 27004216 TI - In silico analysis of polymorphisms in microRNAs that target genes affecting aerobic glycolysis. AB - BACKGROUND: Cancer cells preferentially metabolize glucose through aerobic glycolysis, an observation known as the Warburg effect. Recently, studies have deciphered the role of oncogenes and tumor suppressor genes in regulating the Warburg effect. Furthermore, mutations in glycolytic enzymes identified in various cancers highlight the importance of the Warburg effect at the molecular and cellular level. MicroRNAs (miRNAs) are non-coding RNAs that posttranscriptionally regulate gene expression and are dysregulated in the pathogenesis of various types of human cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes may affect miRNA biogenesis, processing, function, and stability and provide additional complexity in the pathogenesis of cancer. Moreover, mutations in miRNA target sequences in target mRNAs can affect expression. METHODS: In silico analysis and cataloguing polymorphisms in miRNA genes that target genes directly or indirectly controlling aerobic glycolysis was carried out using different publically available databases. RESULTS: miRNA SNP2.0 database revealed several SNPs in miR-126 and miR-25 in the upstream and downstream pre-miRNA flanking regions respectively should be inserted after flanking regions and miR-504 and miR-451 had the fewest. These miRNAs target genes that control aerobic glycolysis indirectly. SNPs in premiRNA genes were found in miR-96, miR-155, miR-25 and miR34a by miRNASNP. Dragon database of polymorphic regulation of miRNA genes (dPORE-miRNA) database revealed several SNPs that modify transcription factor binding sites (TFBS) or creating new TFBS in promoter regions of selected miRNA genes as analyzed by dPORE-miRNA. CONCLUSIONS: Our results raise the possibility that integration of SNP analysis in miRNA genes with studies of metabolic adaptations in cancer cells could provide greater understanding of oncogenic mechanisms. PMID- 27004217 TI - Comparison of bone marrow sparing intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in carcinoma of anal canal: a prospective study. AB - BACKGROUND: Chemoradiation (CRT) is the standard of care in anal canal carcinoma. CRT leads to suppression of iliac bone marrow (BM) leading to hematological toxicity. Intensity modulated radiation therapy (IMRT) technique can be used to decrease radiation dose to iliac BM and thus decrease haematological toxicity. This study aims to compare the haematological and gastrointestinal toxicity in BM sparing IMRT with three-dimensional conformal radiation therapy (3DCRT) in anal carcinoma patients. METHODS: Twenty untreated, biopsy proven anal canal carcinoma (stages I-III) patients were randomized into IMRT and 3DCRT arm. All patients received CRT with 45 Gy in 25 fractions at 1.8 Gy/fraction and weekly concurrent inj. cisplatin and 5-FU. Patients were evaluated for acute haematological and gastrointestinal toxicity during treatment. Additional dosimetric comparison was made between the two groups. RESULTS: Incidence of worst hematological toxicity grade II (GII) and GIII was seen in 40% [4] vs. 30% [3] and 20% [2] vs. 0% [0] respectively, in 3DCRT and IMRT group. However these did not come as statistically significant (P=0.228). Incidence of worst gastrointestinal toxicity during treatment in terms of GII was 30% [3] vs. 50% [5] and GIII was 60% [6] vs. 0% [0] in 3DCRT and IMRT group respectively (P=0.010). Other parameters indicating better tolerance of treatment with IMRT arm than 3DCRT arm were lesser need for administration of parenteral fluid 10% [1] vs. 60% [6] (P=0.019); lesser need for blood transfusion 0% [0] vs. 20% [2] (P=0.060) in IMRT arm than in 3DCRT arm respectively. Patient requiring supportive care during treatment like need for anti-motility drugs and WHO. Step II analgesics also favored IMRT arm. Overall treatment time for Arm B (33.40 days) was less than what was seen in Arm A patients (36.8 days), although difference was not statistically significant (P=0.569). In terms of dosimetric analysis, arm B with the use of IMRT showed superiority over arm A with 3DCRT. The mean volume of bladder receiving >=30 and 40 Gy respectively was 100% and 96% for group A (3DCRT) as compared to 68% and 31% for the group B (IMRT) (P<0.05). For bowel, although, the V30 and V40 for 3DCRT versus IMRT respectively were 51% and 27% vs. 27% and 13%, statistical significance was not reached (P>0.05). There was also less mean BM receiving >=10 Gy (80.4%) and >=20 Gy (65.6%) for group B using IMRT, than in 3DCRT (group A) were it was 91% and 73% respectively. Although for V10 it was significant (P=0.04), it did not reach statistical significance for the V20 (P=0.550). CONCLUSIONS: Preliminary outcomes suggest that BM sparing IMRT for anal canal cancers can decrease both haematological and gastrointestinal toxicity as compared to 3DCRT and thus CRT course can be completed effectively without treatment breaks. PMID- 27004218 TI - Comparative study of tumor markers in patients with colorectal carcinoma before and after chemotherapy. AB - BACKGROUND: Colorectal carcinoma (CRC), the second leading cause of cancer related deaths in US, has a rising time-trend in India. Tumour markers in CRC are extensively researched, and there's still debate on their diagnostic and prognostic values. METHODS: In this hospital-based longitudinal study in north India, 51 male diagnosed CRC cases (pre-chemotherapy) were contrasted against 50 age and sex matched controls. Nine biomarkers: carcinoembryonic antigen (CEA), prolactin (PRL), alfa feto protein (AFP), total human chorionic gonadotropin (hCG), cancer antigen-125 (CA-125), serum testosterone, prostate specific antigen (PSA) and ferritin were measured by direct chemiluminescence technique. Further, follow-up was done on 47 cases after treatment with six cycles of 5-flurouracil (5-FU) and oxaliplatin. RESULTS: Mean serum CEA (case: 5.94+/-8.27 ng/mL, control: 2.5+/-0.79 ng/mL, P<0.05), PRL (case: 28.12+/-13.39 ng/mL, control: 14.24+/-13.13 ng/mL, P<0.0001), AFP (case: 10.9+/-6.65 ng/mL, control: 4.02+/ 1.26 ng/mL, P<0.0001) levels were significantly raised in CRC cases compared to controls. On the contrary, mean testosterone level (P<0.05) was lower among the cases. After chemotherapy, the mean serum CEA (P<0.05), AFP (P<0.0001) and CA-125 (P<0.05) levels among the cases decreased significantly compared to their pretreatment levels. CONCLUSIONS: The present study strongly indicates the role of CEA, PRL, AFP, CA-125 and testosterone as important biomarkers in male CRC patients from north India. Further, AFP, CA-125 and CEA may be used to assess the effectiveness of chemotherapy in such patients. PMID- 27004219 TI - Mental health issues amongst medical students in Asia: a systematic review [2000 2015]. AB - BACKGROUND: Studies have shown that the stress experienced by medical students is far greater than that experienced by other university students. In this study, we aim to understand the consequent mental health issues that are experienced by medical students, particularly in Asia, via a systematic review of the current literature. METHODS: Initial searches on MEDLINE, Embase and SpringerLink came up with a total of 1,033 unique articles. Studies not focusing on medical students alone, not mentioning mental health issues or not containing prevalence values were excluded. RESULTS: We included 14 articles in our analysis. ADs had a prevalence of 7.04% (100/1,420). Depression was prevalent in 11.0% (1,115/10,147) of students. A total of 12.9% (54/420) and 12.9% (41/319) of male and female medical students respectively were screened for depression. Preclinical students were also 1.63 times more likely to be depressed compared to clinical students, with 98.0% (48/49) pre-clinical students having screened for depression, compared to 60% (27/45) clinical students. Home staying medical students are 1.33 times more likely to be depressed compared to hostel-stayers, with 12.1% (29/239) of home stayers being depressed compared to 9.2% (37/402) of hostel stayers. CONCLUSIONS: We found that mental health issues affect a significant proportion of medical students and they are more prevalent in certain subpopulations of medical students. Our data revealed that preclinical and home staying students can be more susceptible to depression. More research should be done regarding this issue. With such information, it is hoped that appropriate interventions can be designed to improve the mental health of medical students. PMID- 27004220 TI - Diagnosis, disease stage, and distress of Chinese cancer patients. AB - BACKGROUND: The objective is to assess how cancer patients know about their diagnosis what they know about their real stage, and the relationship between cancer stage and psychological distress. METHODS: A questionnaire including the Distress Thermometer was delivered to 422 cancer inpatients. Multivariate logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Most of patients (68.7%) knew the bad news immediately after diagnosis. Half of patients knew their diagnosis directly from medical reports. Nearly one third of patients were informed by doctors. Cancer stages, which patients believed, differed significantly from their real disease stages (P<0.001). Over half of patients did not know their real disease stages. Patients with stage I-III cancer were more likely to know their real disease stage than patients with stage IV cancer (P<0.001). Distress scores of cancer patients were determined by the real cancer stage (P=0.012), not the stage which patients believed. CONCLUSIONS: Although most of participants knew the bad news immediately after diagnosis, less than half of them knew their real disease stage. Patient with stage I-III cancer was more likely to know the real disease stage and had a DT score <4 than patient with stage IV disease. PMID- 27004221 TI - Toxicity and early outcomes of regorafenib in multiply pre-treated metastatic colorectal adenocarcinoma-experience from a tertiary cancer centre in India. AB - BACKGROUND: Regorafenib is a multikinase inhibitor (MKI) approved for use in multiply pre-treated metastatic colorectal cancers (mCRC). To the best of our knowledge, this is the first report of regorafenib from India. MATERIALS AND METHODS: Records of 23 cases treated with regorafenib at our centre between June 2013 till September 2015 were reviewed. All had received at least two non cross resistant lines of therapy prior to regorafenib. Toxicity was recorded using CTCAE version 4.03. Responses were assessed using RECIST 1.1 criteria. Response evaluation was done every three months or earlier if clinically indicated. Five patients were still on therapy at the time of this report. RESULTS: The median age was 50 years. Thirty-nine percent (9/23) had upfront metastatic disease. Twenty-six percent (6/23) and 39% (9/23) patients had received prior treatment with cetuximab and bevacizumab respectively. Mean duration of regorafenib treatment was 3.8 months. At least one grade III/IV toxicity was noted in 65% (15/23) cases. The most common were handfoot syndrome (HFS) and fatigue seen in 86.9% (20/23) patients. Grade II and III HFS was seen in 65% patients. One patient required stoppage of treatment due to grade III hepatotoxicity. Dose reduction was required for 86.9% (20/23) patients. Best response noted was stable disease in 34.8% (8/23), partial response in 8.7% (2/23) patients and progression in 56.5% (13/23). Median progression free survival was 3 months and median follow up was 4.5 months. CONCLUSIONS: Regorafenib, although an effective treatment strategy in multiply pre-treated mCRC, is associated with significant side effects. PMID- 27004222 TI - Determining the frequency of sporadic cases of rare X-linked disorders. AB - This paper gives formulae for calculating the gene frequency, incidence and proportion of sporadic cases of rare X-linked recessive disorders, taking account of the possibility of early recognition of carriers and fitness of affected males. PMID- 27004223 TI - New horizons of non-emergent use of extracorporeal membranous oxygenator support. AB - The expansion of the extra corporeal membrane oxygenation (ECMO) use and its indication is strikingly increased in the past few years. ECMO use expanded to lung transplantation, difficult general thoracic resections, transcatheter aortic valve replacement (TAVR) and LVAD implantation. Here we will discuss the indications and the outcomes of non-emergent use of ECMO. PMID- 27004225 TI - Reshaping and aggregating data: an introduction to reshape package. AB - It is common that data format extracted from clinical database does not meet the purpose of statistical analysis. In clinical research, variables are frequently measured repeatedly over the follow-up period. Such data can be displayed either in wide or long format. Transformation between these 2 forms can be challenging by hand. Fortunately, there are sophisticated packages in R environment. Data frame should firstly be melted and then casted to format that you want. Aggregation over unique combination of id variables is also allowable. Additionally, the article also introduces 2 functions colsplit() and funstofun() that can be useful in some circumstances. PMID- 27004224 TI - Rethinking autonomy: decision making between patient and surgeon in advanced illnesses. AB - Patients with advanced illness such as advanced stage cancer presenting with the need for possible surgical intervention can be some of the most challenging cases for a surgeon. Often there are multiple factors influencing the decisions made. For patients they are facing not just the effects of the disease on their body, but the stark realization that the disease will also limit their life. Not only are these factors a consideration when patients are making decisions, but also the desire to make the decision that is best for themselves, the autonomous decision. Also included in this process for the patient facing the possible need for an intervention is the surgeon. While patient autonomy remains one of the main principles within medicine, guiding treatment decisions, there is also the surgeon's autonomy to be considered. Surgeons determine if there is even a possible intervention to be offered to patients, a decision making process that respects surgeons' autonomous choices and includes elements of paternalism as surgeons utilize their expertise to make decisions. Included in the treatment decisions that are made and the care of the patient is the impact patients' outcomes have on the surgeon, the inherent drive to be the best for the patient and desire for good outcomes for the patient. While both the patient's and surgeon's autonomy are a dynamic interface influencing decision making, the main goal for the patient facing a palliative procedure is that of making treatment decisions based on the concept of shared decision making, always giving primary consideration to the patient's goals and values. Lastly, regardless of the decision made, it is the responsibility of surgeons to their patients to be a source of support through this challenging time. PMID- 27004226 TI - How to improve assessment of balance in baseline characteristics of clinical trial participants-example from PROSEVA trial data? AB - The randomization process is expected to balance assignment between the groups, independent to the participant and/or investigator, and as such avoids systematic error. However, it is recognized that groups assigned through the randomization process are not completely the same. Generally, a table with baseline characteristics is provided, where investigators report demographic and pertinent clinical variables based on the random group assignment and P values for the each variable in attempt to either support the balanced assignment or to indicate that the balance between groups was not ideal. The recently published PROSEVA trial showed more than 50% relative risk reduction of 28-day mortality among ARDS patients in the prone group compared to the supine group. In order to demonstrate a novel approach and exemplify how imbalance in baseline characteristics between groups could have potentially contributed to the large observed effect, we pooled pertinent baseline clinical variables from the trial in a meta-analysis-like manner. In addition to the quantification, we assigned the variable's "quality" of probable effect on the outcome as likely beneficial or harmful. After pooling pertinent dichotomous variables by the probability of their effect on the outcome, it appeared that approximately 37% (18% to 60%) of the observed PROSEVA trial effect could have been due to differences in baseline clinical characteristics. The main limitation of this approach is that all variables are assumed to have similar weights on the outcome. Interestingly, the weights of beneficial and harmful effects on the outcome were very similar. The proposed method of assessment of potential imbalance between the intervention groups assesses not only the magnitude of the difference, but rather the pooled probability of beneficial or harmful effect towards outcome, as well. As such, it could be useful as a secondary measure for the assessment of imbalance in the trials with the unexpectedly large observed effects. PMID- 27004227 TI - Targeting epidermal growth factor receptor for head and neck squamous cell carcinoma: still lost in translation? AB - The epidermal growth factor receptor (EGFR) is preferentially expressed in head and neck squamous cell carcinoma (HNSCC), and is a promising therapeutic target. Yet other than cetuximab, no agent targeting EGFR has been approved for this disease, and none has shown benefit over the standard of care. Several randomized trials of antibody and small molecule agents have found no new indication for these agents, despite their initial promise. In this review, we examine the major clinical evidence and discuss potential future developments of translational science in this area, including use of these agents in risk-stratified subgroups, inhibition of downstream/parallel targets, and combination with immunotherapy. PMID- 27004228 TI - Forget skin scrubbing and other antiseptics: prevent catheter related infections using chlorhexidine plus alcohol. PMID- 27004229 TI - Fractionated radiotherapy combined with PD-1 pathway blockade promotes CD8 T cell mediated tumor clearance for the treatment of advanced malignancies. PMID- 27004230 TI - The evolving role of renal mass biopsy. PMID- 27004231 TI - Postmenopausal vaginal bleeding as initial presentation of gastric cancer: a case report with literature review of prognostic factors and treatment of krukenberg tumor. AB - Postmenopausal vaginal bleeding is a rare presentation of Krukenberg tumor (KT). Here we report a very unusual presentation of gastric cancer in a postmenopausal female patient, who presented with complaint of vaginal bleeding. She was found to have KT of the left ovary after total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). She was subsequently diagnosed with primary gastric cancer. To the best of our knowledge, this is the first case report of KT with a primary T1a gastric cancer and no evidence of metastasis anywhere else except for large ovarian mass. PMID- 27004232 TI - STARD 2015: updated reporting guidelines for all diagnostic accuracy studies. PMID- 27004233 TI - Attentional Demand of a Virtual Reality-Based Reaching Task in Nondisabled Older Adults. AB - Attention during exercise is known to affect performance; however, the attentional demand inherent to virtual reality (VR)-based exercise is not well understood. We used a dual-task paradigm to compare the attentional demands of VR based and non-VR-based (conventional, real-world) exercise: 22 non-disabled older adults performed a primary reaching task to virtual and real targets in a counterbalanced block order while verbally responding to an unanticipated auditory tone in one third of the trials. The attentional demand of the primary reaching task was inferred from the voice response time (VRT) to the auditory tone. Participants' engagement level and task experience were also obtained using questionnaires. The virtual target condition was more attention demanding (significantly longer VRT) than the real target condition. Secondary analyses revealed a significant interaction between engagement level and target condition on attentional demand. For participants who were highly engaged, attentional demand was high and independent of target condition. However, for those who were less engaged, attentional demand was low and depended on target condition (i.e., virtual > real). These findings add important knowledge to the growing body of research pertaining to the development and application of technology-enhanced exercise for elders and for rehabilitation purposes. PMID- 27004234 TI - Detection of Vaccine-Induced Antibodies to Ebola Virus in Oral Fluid. AB - Blood sampling to assess production of antigen-specific antibodies after immunization is commonly performed, but it presents logistical difficulties for trials carried out during an infectious disease outbreak. In this study, we show that antibodies may be reliably detected in oral fluid collected in a minimally invasive manner without use of sharps. Clinical Trials Registration. NCT02240875. PMID- 27004235 TI - Adolescent Research Participants' Descriptions of Medical Research. AB - BACKGROUND: Evidence shows both a tendency for research participants to conflate research and clinical care and limited public understanding of research. Conflation of research and care by participants is often referred to as the therapeutic misconception. Despite a lack of evidence, few studies have explicitly asked participants, and especially minors, to explain what they think research is and how they think it differs from regular medical care. METHODS: As part of a longer semi-structured interview evaluating assent and parental permission for research, adolescent research participants, including adolescents with illnesses and healthy volunteers (N=177), and their parents (N=177) were asked to describe medical research in their own words and say whether and how they thought being in medical research was different from seeing a regular doctor. Qualitative responses were coded and themes identified through an iterative process. RESULTS: When asked to describe medical research, the majority described research in terms of its goals of helping to advance science, develop treatments and medicines, and help others; fewer described research as having the goal of helping particular research participants, and fewer still in terms of the methods used in research. The majority of teen and parent respondents said being in research is different than seeing a regular doctor and explained this by describing different goals, different or more procedures, differences in the engagement of the doctors/researchers, and in logistics. CONCLUSIONS: Adolescents participating in clinical research and their parents generally describe medical research in terms of its goals of advancing science and finding new medicines and treatments, sometimes in combination with helping the enrolled individuals. The majority perceives a difference between research and regular medical care and described these differences in various ways. Further exploration is warranted about how such perceived differences matter to participants and how this understanding could be used to enhance informed consent and the overall research experience. PMID- 27004236 TI - Clocks within Clocks: Timing by Coincidence Detection. AB - The many existent models of timing rely on vastly different mechanisms to track temporal information. Here we examine these differences, and identify coincidence detection in its most general form as a common mechanism that many apparently different timing models share, as well as a common mechanism of biological circadian, millisecond and interval timing. This view predicts that timing by coincidence detection is a ubiquitous phenomenon at many biological levels, explains the reports of biological timing in many brain areas, explains the role of neural noise at different time scales at both biological and theoretical levels, and provides cohesion within the timing field. PMID- 27004237 TI - Congenital duodenal web: successful management with endoscopic dilatation. AB - BACKGROUND AND STUDY AIMS: Congenital duodenal web (CDW) is an uncommon cause of duodenal obstruction and endoscopic balloon dilatation has been reported in just eight pediatric cases to date. Here we are reporting three cases of CDW managed successfully with balloon dilatation. CASES AND METHODS: In 2014 we diagnosed three cases of CDW on the basis of typical radiological and endoscopic findings. Endoscopic balloon dilatation was done under conscious sedation with a through the-scope controlled radial expansion (CRE) balloon. RESULTS: All three children presented late (median age 8 [range 2 - 9] years) with bilious vomiting, upper abdominal distension, and failure to thrive. One of them had associated Down syndrome and another had horseshoe kidney. In all cases, CDW was observed in the second part of the duodenum beyond the ampulla, causing partial duodenal obstruction. After repeated endoscopic dilatation (2 - 4 sessions), all three patients became asymptomatic. None of the patients experienced complications after balloon dilatation. CONCLUSIONS: Duodenal diaphragm should be suspected in patients with abdominal distension with bilious vomiting, even in relatively older children. Endoscopic balloon dilatation is a simple and effective method of treating this condition. PMID- 27004238 TI - Endosonographers' approach to delivering a diagnosis of pancreatic cancer: obligated but undertrained. AB - BACKGROUND AND STUDY AIMS: No data are available on the practice patterns of endosonographers as they pertain to the disclosure of a pancreatic cancer diagnosis. We sought to understand the current practice and coping strategies of physicians who perform endoscopic ultrasound (EUS) procedures in patients with suspected pancreatic cancer. METHODS: This study used a nonexperimental, cross sectional survey design. A total of 707 endosonographers were contacted and asked to complete an online survey encompassing both demographic and practice data. In addition, participants had the option to complete a second survey assessing common coping strategies. RESULTS: A total of 152 physicians (22 %) participated in the study. The sample was split between community (47 %) and academic centers (53 %). A total of 92 % of the respondents felt an obligation to share a cancer diagnosis when it was available to them; however, only 45 % felt they were adequately trained to do so. Comfort levels were higher in those who performed more than 200 EUS procedures annually and in those practicing for longer than 5 years (P = 0.044). A total of 98 physicians (64.5 %) also completed the Brief COPE questionnaire, and the results indicated that the more experienced endosonographers were less likely to experience emotional distress when disclosing a cancer diagnosis. CONCLUSION: The comfort level for disclosing a pancreatic cancer diagnosis after EUS appears to be higher in experienced endosonographers (> 5 years in practice) and in those who conduct a higher volume of procedures. Although the majority of endosonographers feel obligated to disclose a cancer diagnosis, the lack of time and proper training is limiting. Formal communication skills training within a gastrointestinal fellowship should be considered. PMID- 27004239 TI - Preoperative diagnosis of cavernous hemangioma presenting with melena using wireless capsule endoscopy of the small intestine. AB - BACKGROUND AND STUDY AIMS: Primary neoplasms of the small intestine are relatively rare in all age groups, accounting for about 5 % of all gastrointestinal tumors 1. Cavernous hemangiomas of the small intestine are also rare, can cause gastrointestinal bleeding, and are extremely difficult to diagnose preoperatively 2. We present a patient who presented with melena and iron deficiency anemia, for whom wireless capsule endoscopy and single-balloon enteroscopy facilitated the diagnosis of cavernous hemangioma. PMID- 27004240 TI - A case of carcinoma in an adenoma of the duodenal minor papilla successfully treated with endoscopic mucosal resection. AB - BACKGROUND AND STUDY AIMS: Endoscopic papillectomy is currently used to treat noninvasive tumors of the papilla of Vater, but it is seldom reported for treatment of similar tumors of the minor papilla. This report describes the case of a 69-year-old female with a tumor located at the duodenal minor papilla. Findings of duodenoscopy, biopsy, and pancreatography indicated that her noninvasive tumor of the minor papilla was suitable for treatment with endoscopic resection. Glycerol-injected endoscopic mucosal resection (EMR) was performed, and the resected material histologically showed carcinoma in the adenoma, negative for neoplastic extension at the cut margin. No complications occurred during the treatment course, and no recurrence has been recognized for 80 months. Unlike the major papilla of Vater, the minor papilla can be lifted up by submucosal injection. Noninvasive epithelial tumors of the duodenal minor papilla without extension to the pancreatic duct can be successfully treated with EMR, as the technique is easy, it is minimally invasive, and it is curative. PMID- 27004241 TI - Risk factors determining the need for second-look endoscopy for peptic ulcer bleeding after endoscopic hemostasis and proton pump inhibitor infusion. AB - BACKGROUND AND STUDY AIMS: The need for routine second-look endoscopy in cases of peptic ulcer bleeding remains uncertain. We investigated risk factors related to the need for second-look endoscopy after endoscopic hemostasis and proton pump inhibitor (PPI) infusion. PATIENTS AND METHODS: We prospectively enrolled 316 patients with peptic ulcer bleeding after endoscopic hemostasis. Second-look endoscopy was scheduled after 72-hour PPI infusion (Day-3 subgroup) or one day early (Day-2 subgroup). If early rebleeding developed within 3 days, emergent second-look endoscopy was conducted. Risk factors for early rebleeding (use of E2(nd) score to predict the need for early second-look endoscopy) and persistent major stigmata in the Day-3 subgroup (use of R2(nd) score to predict the need for routine second-look endoscopy) were analyzed using univariable and multivariable regression. RESULTS: Excluding 10 of 316 patients with early rebleeding, the rate of persistent major stigmata was lower in the Day-3 subgroup than in the Day-2 subgroup (4.8 % vs. 15.4 %, P = 0.002). Endoscopic epinephrine-injection monotherapy and hypoalbuminemia < 3.0 g/dL were two independent risk factors for early rebleeding (P <= 0.05). The Forrest Ia-Ib type and hypoalbuminemia < 3.5 g/dL were two independent risk factors for persistent major stigmata on the day-3 second-look endoscopy (P < 0.05). The E2(nd) score was highly accurate for prediction of early rebleeding (AUROC 0.86; 95 % CI, 0.73~0.99), and the R2(nd) score could predict persistent major stigmata at second-look endoscopy (AUROC 0.84; 95 % CI, 0.69~0.99). CONCLUSIONS: For patients with peptic ulcer bleeding, E2(nd) and R2(nd) scores can indicate the need for early and routine second-look endoscopy, respectively (Trial registration identifier: NCT02197039). PMID- 27004242 TI - The efficacy of peroral cholangioscopy for difficult bile duct stones and indeterminate strictures: a systematic review and meta-analysis. AB - BACKGROUND AND STUDY AIMS: Current evidence supporting the efficacy of peroral cholangioscopy (POC) in the evaluation and management of difficult bile duct stones and indeterminate strictures is limited. The aims of this systematic review and meta-analysis were to assess the following: the efficacy of POC for the therapy of difficult bile duct stones, the diagnostic accuracy of POC for the evaluation of indeterminate biliary strictures, and the overall adverse event rates for POC. PATIENTS AND METHODS: Patients referred for the removal of difficult bile duct stones or the evaluation of indeterminate strictures via POC were included. Search terms pertaining to cholangioscopy were used, and articles were selected based on preset inclusion and exclusion criteria. Quality assessment of the studies was completed with a modified Newcastle-Ottawa Scale. After critical literature review, relevant outcomes of interest were analyzed. Meta-regression was performed to examine potential sources of between-study variation. Publication bias was assessed via funnel plots and Egger's test. RESULTS: A total of 49 studies were included. The overall estimated stone clearance rate was 88 % (95 % confidence interval [95 %CI] 85 % - 91 %). The accuracy of POC was 89 % (95 %CI 84 % - 93 %) for making a visual diagnosis and and 79 % (95 %CI 74 % - 84 %) for making a histological diagnosis. The estimated overall adverse event rate was 7 % (95 %CI 6 % - 9 %). CONCLUSIONS: POC is a safe and effective adjunctive tool with endoscopic retrograde cholangiopancreatography (ERCP) for the evaluation of bile duct strictures and the treatment of bile duct stones when conventional methods have failed. Prospective, controlled clinical trials are needed to further elucidate the precise role of POC during ERCP. PMID- 27004243 TI - Endoscopic ultrasound-guided gastrojejunostomy with a lumen-apposing metal stent: a multicenter, international experience. AB - BACKGROUND: Surgical gastrojejunostomy and enteral self-expanding metal stents are efficacious for the management of gastric outlet obstruction but limited by high complication rates and short-term efficacy. Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) is a novel alternative option. PATIENTS AND METHODS: Patients who underwent EUS-GJ between March 2014 and September 2015 as part of a prospective multicenter registry at four academic centers in two countries were included. Technical success was defined as successful placement of a gastrojejunal lumen-apposing metal stent. Clinical success was defined as the ability of the patient to tolerate an oral diet. Post-procedural adverse events were recorded. RESULTS: The study included 26 patients, of whom 11 (42 %) were male. Technical success was achieved in 24 patients (92 %). Clinical success was achieved in 22 patients (85 %). Of the 4 patients in whom clinical success was not achieved, 2 had persistent nausea and vomiting despite a patent EUS-GJ and required enteral feeding for nutrition, 1 died before the initiation of an oral diet, and 1 underwent surgery for suspected perforation. Adverse events, including peritonitis, bleeding, and surgery, occurred in 3 patients (11.5 %). CONCLUSION: EUS-GJ is an emerging procedure that has efficacy and safety comparable with those of current therapies and should hold a place as a new minimally invasive option for patients with gastric outlet obstruction. Clinical trial identification number: NCT01522573. PMID- 27004244 TI - Outcomes of acute upper gastrointestinal bleeding in relation to timing of endoscopy and the experience of endoscopist: a tertiary center experience. AB - INTRODUCTION: Patients with gastrointestinal bleeding admitted out of hours or at the weekends may have an excess mortality rate. The literature reports around this are conflicting. AIMS AND METHODS: We aimed to analyze the outcomes of emergency endoscopies performed out of hours and over the weekends in our center. We retrospectively analyzed data from April 2008 to June 2012. RESULTS: A total of 507 'high risk' emergency gastroscopies were carried out over the study period for various indications. Patients who died within 30 days of the index procedure [22 % (114 /510)] had a significantly higher Rockall score (7.6 vs. 6.0, P < 0.0001), a higher American Society of Anesthesiologists (ASA) status (3.5 vs. 2.7, P < 0.001), and a lower systolic blood pressure (BP) at the time of the examination (94.8 vs 103, P = 0.025). These patients were significantly older (77.7 vs. 67.5 years, P = 0.006), and required more blood transfusion (5.9 versus 3.8 units). Emergency out-of-hours endoscopy was not associated with an increased risk of death [relative risk (RR) 1.09, 95 % confidence interval (CI) 1.12 - 1.95]. Whether the examination was carried out by a senior specialist registrar (senior trainee) or a consultant made no difference to the survival of the patient (RR 0.98, CI 0.77 - 1.32). CONCLUSION: Higher pre-endoscopy Rockall score and ASA status contributed significantly to the 30-day mortality following upper gastrointestinal bleeding, whereas lower BP tended towards significance. Outcomes did not vary with the time of the endoscopy nor was there any difference between a consultant and a senior specialist registrar led service. PMID- 27004245 TI - Endoscopic ultrasound-guided hepaticogastrostomy using a 6-F cystotome and 12-cm covered metal stent. AB - BACKGROUND AND STUDY AIMS: An iincreasing number of reports describe endoscopic ultrasound-guided hepaticogastrostomy for malignant biliary obstruction in patients with endoscopic retrograde cholangiopancreatography failure. However, this procedure has not yet been standardized; as a result, the rate of adverse events, including bile leakage and stent migration, is relatively high. Here, we report our experience with four cases of endoscopic ultrasound-guided hepaticogastrostomy performed according to our institutional procedure. PMID- 27004246 TI - Insufflation with carbon dioxide reduces pneumoperitoneum after percutaneous endoscopic gastrostomy (PEG): a randomized controlled trial. AB - BACKGROUND AND STUDY AIMS: Pneumoperitoneum following PEG placement has been reported in up to 60 % of cases, and while usually benign and self-limited, it can lead to evaluation for suspected perforation. This study was designed to determine whether using CO2 compared to ambient air for insufflation during PEG reduces post-procedure pneumoperitoneum. PATIENTS AND METHODS: Prospective, double-blind, randomized trial of 35 consecutive patients undergoing PEG at a single academic medical center. Patients were randomized to insufflation with CO2 or ambient air. The primary outcome was pneumoperitoneum determined by left lateral decubitus abdominal x-rays 30 minutes after PEG placement. Secondary endpoints included abdominal distention, pain, and bloating. RESULTS: PEG was successfully placed in 17 patients using CO2 and 18 patients using ambient air. Three patients in each arm were unable or declined to have x-rays completed and were excluded. Pneumoperitoneum was identified in 2/14 (14.3 %) using CO2 and 8/15 (53.3 %) using ambient air (P = 0.05). There was no significant difference in abdominal distention, visual analog scale (VAS) scores for pain or bloating between CO2 and ambient air. CONCLUSION: Utilizing CO2 significantly reduces the frequency of post-procedural pneumoperitoneum compared to use of ambient air during PEG placement, with no difference in waist circumference, pain or bloating between CO2 and ambient air. CO2 appears to be safe and effective for use and may be the insufflation agent of choice during PEG. PMID- 27004247 TI - Biodegradable stents for the treatment of bowel strictures in Crohn's disease: technical results and challenges. AB - BACKGROUND AND STUDY AIMS: In patients with Crohn's disease, the idea of biodegradable stents for treatment of bowel strictures with limited effect of endoscopic balloon dilation is tempting and initial results have been promising. The aim of this study was to evaluate the technical and clinical success of biodegradable stents for treatment of inflamed Crohn's strictures refractory to endoscopic balloon dilatation. PATIENTS AND METHODS: Consecutive patients treated with biodegradable stents due to Crohn's disease and inflamed bowel strictures refractory to endoscopic balloon dilatation were included. Technical and clinical success were evaluated. RESULTS: Six patients were included in the study. Technical success was obtained in five patients (83 %). Clinical success was limited to one patient (20 %); failure was observed due to mucosal overgrowth (n = 2), stent migration (n = 1), and stent collapse (n = 1). CONCLUSIONS: In Crohn's disease, it is technically feasible to treat bowel strictures with biodegradable stents. However, we have stopped using biodegradable stents due to lack of clinical success and side effects such as mucosal overgrowth and stent collapse. PMID- 27004248 TI - Stent for Crohn's disease strictures: Which one and when? PMID- 27004249 TI - Hill classification is superior to the axial length of a hiatal hernia for assessment of the mechanical anti-reflux barrier at the gastroesophageal junction. AB - BACKGROUND AND STUDY AIMS: The pathogenesis of gastroesophageal reflux disease (GERD) is multifactorial, including the mechanical anti-reflux barrier of the gastroesophageal junction. This barrier can be evaluated endoscopically in two ways: by measuring the axial length of any hiatal hernia present or by assessing the gastroesophageal flap valve. The endoscopic measurement of axial length is troublesome because of the physiological dynamics in the area. Grading the gastroesophageal flap valve is easier and has proven reproducible. The aim of the present study was to compare the two endoscopic grading methods with regard to associations with GERD. PATIENTS AND METHODS: Population-based subjects underwent endoscopic examination assessing the axial length of hiatus hernia, the gastroesophageal flap valve using the Hill classification, esophagitis using the Los Angeles (LA) classification, and columnar metaplasia using the Z-line appearance (ZAP) classification. Biopsies were taken from the squamocolumnar junction to assess the presence of intestinal metaplasia. Symptoms were recorded with the validated Abdominal Symptom Questionnaire. GERD was defined according to the Montreal definition. RESULTS: In total, 334 subjects were included in the study and underwent endoscopy; 86 subjects suffered from GERD and 211 presented no symptoms or signs of GERD. Based on logistic regression, the estimated area under the curve statistic (AUC) for Hill (0.65 [95 %CI 0.59 - 0.72]) was higher than the corresponding estimate for the axial length of a hiatal hernia (0.61 [95 %CI 0.54 - 0.68]), although the difference was not statistically significant (P = 0.225). CONCLUSION: From our data, and in terms of association with GERD, the Hill classification was slightly stronger compared to the axial length of a hiatal hernia, but we could not verify that the Hill classification was superior as a predictor. The Hill classification may replace the axial length of a hiatal hernia in the endoscopic assessment of the mechanical anti-reflux barrier of the gastroesophageal junction. PMID- 27004250 TI - Volumetric laser endomicroscopy can target neoplasia not detected by conventional endoscopic measures in long segment Barrett's esophagus. AB - Methods and study aims: The incidence of esophageal cancer is rising despite increased surveillance efforts. Volumetric laser endomicroscopy (VLE) is a new endoscopic imaging tool that can allow for targeted biopsy of neoplasia in Barrett's esophagus. We report a series of 6 patients with long-segment Barrett's esophagus ( > 3 cm), who underwent a session of endoscopy with volumetric laser endomicroscopy, after a separate prior session of standard high-definition endoscopy with narrow band imaging (NBI) and random biopsies that did not reveal neoplasia. In all six patients, the first endoscopy was the index endoscopy diagnosing the Barrett's esophagus. All VLE exams were performed within 6 months of the previous endoscopy. In five patients, VLE-targeted biopsy resulted in upstaged disease/diagnosed dysplasia that then qualified the patient for endoscopic ablation therapy. In one patient, VLE localized a focus of intramucosal cancer that allowed for curative endoscopic mucosal resection. This case series shows that endoscopy with VLE can target neoplasia that cannot be localized by high-definition endoscopy with NBI and random biopsies. PMID- 27004251 TI - Ileal follicular lymphoma with atypical endoscopic findings. AB - A 72-year-old woman presented with symptomatic anemia without abdominal symptoms. She had no history of abdominal surgery or use of non-steroidal anti-inflammatory drugs. Enhanced computed tomography of the abdomen revealed swelling of multiple intraperitoneal lymph nodes and a high density of mesenteric adipose tissue. Fluorodeoxyglucose (FDG-) positron emission tomography showed high FDG accumulation at the intraperitoneal lymph nodes. Double-balloon enteroscopy detected severe stenosis with an annular ulcer in the lower ileum. She was diagnosed with ileal follicular lymphoma based on histologic examination and fluorescence in situ hybridization analysis of the biopsy specimen. The ileal ulcer was successfully treated by chemotherapy with rituximab and bendamustine for 1 year. We strongly recommend consideration of gastrointestinal follicular lymphoma in the differential diagnosis of annular ulcers in the small intestine. PMID- 27004252 TI - An explorative study from the Norwegian Quality Register Gastronet comparing self estimated versus registered quality in colonoscopy performance. AB - BACKGROUND AND STUDY AIMS: The value of a colonoscopy quality assurance (QA) register may be questioned if it brings no new information on which to act for quality improvement, e. g. if self-assessed quality of colonoscopy performance correlates perfectly with registered performance. PATIENTS AND METHODS: In this explorative study, 39 (33 Norwegian and 6 Swedish) out of 99 new endoscopists joining the Norwegian QA register Gastronet from 2008 to 2013 responded to an invitation to fill in a questionnaire for self-assessment of cecal intubation rate, polyp detection rate for polyps >= 5 mm (PDR-5 mm), withdrawal time, total examination time, and rates for severely painful and pain-free colonoscopies before receiving their first-time feedback of actually registered results from Gastronet. A linear regression analysis was applied to explore the correlation between experience level and quality of estimation. RESULTS: We included 2654 colonoscopies in our study. Endoscopists underestimated their cecal intubation rate (estimated 88.8 %, registered 93.1 %, P < 0.001), total procedure time (estimated 31.7 minutes, registered 37.2 minutes, P = 0.014), withdrawal time (estimated 9.8 minutes, registered 14.4 minutes, P = 0.006) and the rate of pain free procedures (estimated 18.3 %, registered 24.5 %, P = 0.001). Pre-study colonoscopy experience was not correlated with estimated quality for any of the indicators. CONCLUSIONS: Apart from overestimation of severely painful examinations, endoscopists most often underestimated their colonoscopy performance. Self-assessed quality of colonoscopy performance may not be a satisfactory substitute for systematic registration of quality and not sufficiently valid to be acted upon. PMID- 27004253 TI - Usefulness of training using animal models for colorectal endoscopic submucosal dissection: is experience performing gastric ESD really needed? AB - BACKGROUND AND STUDY AIMS: Despite the clinical advantages of colorectal endoscopic submucosal dissection (ESD), an effective training system, especially for Western endoscopists, has been challenging to establish. Herein, we propose a novel training program using ex vivo animal models and evaluate the learning curve of colorectal ESD trainees without gastric ESD experience. PATIENTS AND METHODS: A total of 80 colorectal lesions were prospectively collected and removed by two novice operators. Before human ESD procedures, they received ESD training using an ex vivo porcine "proximal colon" model, which simulates a lumen with many folds and flexions. To assess the validity of our training system, the self-completion and en bloc R0 resection rates, the operation time, and prevalence of complications were compared between the first and latter period. Moreover the factors associated with prolonged operation time were evaluated. RESULTS: The overall rates of self-completion and en bloc R0 resection were 98 % (78/80) and 100 % (80/80), respectively. The operation time during the first period was significantly longer than that during the latter period (86 +/- 50 minutes vs. 60 +/- 36 minutes, P = 0.01). Regarding complications, only two cases of perforations and delayed hemorrhage were observed during the first period; however, all of the complications were successfully managed endoscopically. The presence of fibrosis was identified as a significant independent predictor of a prolonged operation time during the first period (coefficient, 5.90; 95 %CI, 2.36 - 9.44, P = 0.002). CONCLUSIONS: Our trainees achieved high rates of self completion and R0 resection without severe complications even during the first 20 cases, suggesting that our training programs using ex vivo animal models are useful for trainees without gastric ESD experience. STUDY REGISTRATION: UMIN000013566. PMID- 27004255 TI - Is capnography mandatory during sedation for endoscopy? PMID- 27004254 TI - Modeling the costs and benefits of capnography monitoring during procedural sedation for gastrointestinal endoscopy. AB - BACKGROUND AND STUDY AIMS: The addition of capnography to procedural sedation/analgesia (PSA) guidelines has been controversial due to limited evidence of clinical utility in moderate PSA and cost concerns. PATIENTS AND METHODS: A comprehensive model of PSA during gastrointestinal endoscopy was developed to capture adverse events (AEs), guideline interventions, outcomes, and costs. Randomized, controlled trials and large-scale studies were used to inform the model. The model compared outcomes using pulse oximetry alone with pulse oximetry plus capnography. Pulse oximetry was assumed at no cost, whereas capnography cost USD 4,000 per monitor. AE costs were obtained from literature review and Premier database analysis. The model population (n = 8,000) had mean characteristics of age 55.5 years, body mass index 26.2 kg/m(2), and 45.3 % male. RESULTS: The addition of capnography resulted in a 27.2 % and 18.0 % reduction in the proportion of patients experiencing an AE during deep and moderate PSA, respectively. Sensitivity analyses demonstrated significant reductions in apnea and desaturation with capnography. The median (95 % credible interval) number needed to treat to avoid any adverse event was 8 (2; 72) for deep and 6 (-59; 92) for moderate. Reduced AEs resulted in cost savings that accounted for the additional upfront purchase cost. Capnography was estimated to reduce the cost per procedure by USD 85 (deep) or USD 35 (moderate). CONCLUSIONS: Capnography is estimated to be cost-effective if not cost saving during PSA for gastrointestinal endoscopy. Savings were driven by improved patient safety, suggesting that capnography may have an important role in the safe provision of PSA. PMID- 27004256 TI - Refractory strictures despite steroid injection after esophageal endoscopic resection. AB - BACKGROUND: Although steroid injection prevents stricture after esophageal endoscopic submucosal dissection (ESD), some patients require repeated sessions of endoscopic balloon dilation (EBD). We investigated the risk for refractory stricture despite the administration of steroid injections to prevent stricture in patients undergoing esophageal ESD. Refractory stricture was defined as the requirement for more than three sessions of EBD to resolve the stricture. In addition, the safety of steroid injections was assessed based on the rate of complications. PATIENTS AND METHODS: We analyzed data from 127 consecutive patients who underwent esophageal ESD and had mucosal defects with a circumferential extent greater than three-quarters of the esophagus. To prevent stricture, steroid injection was performed. EBD was performed whenever a patient had symptoms of dysphagia. RESULTS: The percentage of patients with a tumor circumferential extent greater than 75 % was significantly higher in those with refractory stricture than in those without stricture (P = 0.001). Multivariate analysis adjusted for age, sex, history of radiation therapy, tumor location, and tumor diameter showed that a tumor circumferential extent greater than 75 % was an independent risk factor for refractory stricture (adjusted odds ratio [OR] 5.49 [95 %CI 1.91 - 15.84], P = 0.002). Major adverse events occurred in 3 patients (2.4 %): perforation during EBD in 2 patients and delayed perforation after EBD in 1 patient. The patient with delayed perforation underwent esophagectomy because of mediastinitis. CONCLUSIONS: A tumor circumferential extent greater than 75 % is an independent risk factor for refractory stricture despite steroid injections. The development of more extensive interventions is warranted to prevent refractory stricture. PMID- 27004257 TI - Gastrointestinal angiodysplasia is associated with significant gastrointestinal bleeding in patients with continuous left ventricular assist devices. AB - BACKGROUND AND STUDY AIMS: Patients with a continuous-flow left ventricular assist device (LVAD) have a 65 % incidence of bleeding events within the first year. The majority of gastrointestinal bleeding (GIB) is from gastrointestinal angiodyplasia (GIAD). The primary aim of the study was to determine whether GIAD was associated with a higher rate of significant bleeding, an increased number of bleeding events per year, and a higher rate of transfusion compared to non-GIAD sources. PATIENTS AND METHODS: This retrospective cohort study included 118 individuals who received a LVAD at a tertiary medical center from 2006 through 2014. Patients were subdivided into GIB and non-GIB for comparison of patient demographics, comorbid conditions, and laboratory data. GIB was further divided into sources of GIB, GIAD, obscure, or non-GIAD to establish severity of bleeding, rate of re-bleeding, and transfusion rate. RESULTS: GIAD is associated with an increased number of bleeding events compared to non-GIAD sources of GIB (2.07 vs 1.23, P = 0.01) and a higher number of bleeding events per year (0.806 vs. 0.455 P = 0.001). GIAD compared to non-GIAD sources of GIB was associated with an increased incidence of major bleeding (100 % vs 60 %, P = 0.006) and increased rates of transfusion (8.8 vs 2.95 units, P = 0.0004). Cox Regression analysis between non-GIB and GIAD demonstrated increased risk with age (P = 0.001), history of chronic kidney disease (P = 0.005), and length of stay after LVAD implantation of more than 45 days (P = 0.04). History of hypertension (P = 0.045), diabetes mellitus (P = 0.016), and male gender was associated with decreased risk (P = 0.04). CONCLUSION: Patients with a continuous-flow LVAD who develop a GIB secondary to GIAD have a higher rate of major bleeding, multiple bleeding events, and require more transfusions to achieve stabilization compared to patients who do not have GIAD. PMID- 27004258 TI - Endoscopic ultrasound-guided fiducial marker placement for image-guided radiation therapy without fluoroscopy: safety and technical feasibility. AB - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS)-guided fiducial marker placement for image-guided radiation treatment (IGRT) is becoming more widespread. Most case series report the procedure performed using fluoroscopy for spatial geometry although the benefits of this are unclear. The aim of our study is to report the technical feasibility, safety, and migration rate of fiducial marker placement in a large cohort of patients with gastrointestinal malignancies who underwent EUS-guided fiducial marker placement for IGRT without fluoroscopy. PATIENTS AND METHODS: A retrospective chart review was performed on all patients referred for EUS-guided fiducial marker placement from 08/1/07 to 7/31/14 at Moffitt Cancer Center. RESULTS: During the study period, 514 patients underwent placement of 1093 gold fiducial markers under EUS-guidance. Two hundred and forty patients with esophageal/gastro-esophageal junction cancer had 405 fiducials placed. In 188 patients with pancreatic ancer, 510 fiducials were placed. In 54 patients with rectal cancer, 103 fiducials were placed and 32 patients had 75 fiducials placed into other gastrointestinal tract lesions. Minor bleeding, which resolved spontaneously, occurred in two patients. Technical difficulty in placing fiducials was noted in 18 patients. Intraprocedural fiducial migration was noted in two patients and only 2/1093 fiducials (.002%) in two esophageal patients migrated as noted on simulation computed tomography scan. CONCLUSIONS: EUS-guided fiducial marker placement without fluoroscopy is technically feasible and safe. There were minimal intraprocedure/post-procedure complications. Imaging at the time of simulation also revealed the migration rate to be extremely low. These results may allow for more widespread adoption of EUS-guided fiducial marker placement. PMID- 27004259 TI - The Evolution of Cooperation is Affected by the Persistence of Fitness Effects, the Neighborhood Size and their Interaction. AB - Evolutionary Game Theory and the Prisoner's Dilemma (PD) Game in particular have been used to study the evolution of cooperation. We consider a population of asexually reproducing, age-structured individuals in a two-dimensional square lattice structure. The individuals employ fixed cooperative or defecting strategies towards their neighbors in repeating interactions to accumulate reproductive fitness. We focus on the effects of the persistence of past interactions and interactive neighborhood size on the evolution of cooperation. We show that larger neighborhood sizes are generally detrimental to cooperation and that the persistence of fitness effects decreases the likelihood of the evolution of cooperation in small neighborhoods. However, for larger neighborhood sizes the persistence effect is reversed. Thus, our study corroborates earlier studies that population structure increases the evolutionary potential for cooperative behavior in a PD paradigm. This finding may explain the heterogeneity of previous results on the effect of neighborhood size and cautions that the persistence of fitness outcomes needs to be considered in analyses of the evolution of cooperative behavior. The persistence of fitness outcomes of pairwise interactions may vary dramatically in biological and social systems and could have profound effects on the evolution of cooperation in various contexts. PMID- 27004260 TI - Adding STING to the Tale of Oncolytic Virotherapy. AB - The identification of STING as a key cytoplasmic innate recognition molecule for DNA viruses whose function is lost in a variety of cancers has coincided with the approval of IMLYGIC for metastatic melanoma. This represents the first replication competent viral therapy approved for the treatment of any cancer in the US. The role of STING pathway in the selectivity of HSV has been addressed for the first time in Xia et al (1). PMID- 27004261 TI - Best Practices for Event-Related Potential Research in Clinical Populations. AB - The event-related potential (ERP) technique has been used for decades to answer important questions about sensory, cognitive, motor, and emotion-related processes in clinical disorders. However, ERP research with clinical populations often involves unique challenges above and beyond the general issues involved in conducting ERP studies in typical research participants. The goal of this paper is to provide an overview of the common challenges that arise in ERP research with clinical populations, including issues in experimental design, recording, analysis, and interpretation of ERPs. In addition, we provide strategies that have proven effective in each of these areas for maximizing the potential of the ERP technique to provide important insights about clinical disorders. The event related potential (ERP) technique has been used for decades to assess sensory, cognitive, motor, and emotion-related processes in individuals with clinical disorders, and it has great promise for yielding new insights in the future. However, many complex methodological challenges arise in applying this technique to clinical populations, and these challenges must be overcome for the ERP technique to live up to its potential. The goal of this paper is to describe some of the most salient challenges and provide effective strategies for dealing with them. Our own experience has been mainly in schizophrenia, but much of the information presented here applies to any clinical population. We focus our discussion on traditional approaches to ERPs, for which methods been refined over many decades. Information about newer approaches, such as time-frequency analysis, can be found elsewhere (1; 2). We begin with a brief overview of the ERP technique, followed by a discussion of the challenges in designing experiments, practical considerations in recording and analysis, and issues in interpreting ERP effects. The present article is necessarily brief and focused, but broader reviews are available elsewhere (3-11). In addition, we strongly recommend the ERP publication guidelines of the Society for Psychophysiological Research as a supplement to the recommendations in this paper (12). PMID- 27004262 TI - A Brief Introduction to the Transduction of Neural Activity into Fos Signal. AB - The immediate early gene c-fos has long been known as a molecular marker of neural activity. The neuron's activity is transformed into intracellular calcium influx through NMDA receptors and L-type voltage sensitive calcium channels. For the transcription of c-fos, neural activity should be strong enough to activate mitogen-activated protein kinase (MAPK) signaling pathway which shows low calcium sensitivity. Upon translation, the auto-inhibition by Fos protein regulates basal Fos expression. The pattern of external stimuli and the valence of the stimulus to the animal change Fos signal, thus the signal reflects learning and memory aspects. Understanding the features of multiple components regulating Fos signaling is necessary for the optimal generation and interpretation of Fos signal. PMID- 27004263 TI - Modification of Gene Expression of Connexins in the Rat Corpus Epididymis by Estradiol Benzoate or Flutamide Exposure at the Early Neonatal Age. AB - Cell-cell direct communication through channel-forming molecules, connexin (Cx), is essential for a tissue to exchange signaling molecules between neighboring cells and establish unique functional characteristics during postnatal development. The corpus epididymis is a well-known androgen-responsive tissue and involves in proper sperm maturation. In the present research, it was attempted to determine if expression of Cx isoforms in the corpus epididymis in the adult is modulated by exposure to estrogenic or anti-androgenic compound during the early postnatal period. The neonatal male rats at 7 days of age were subcutaneously injected by estradiol benzoate (EB) at low-dose (0.015 mg/kg body weight) or high dose (1.5 mg/kg body weight) or flutamide (Flu) at low-dose (500 mg/kg body weight) or high-dose (50 mg/kg body weight). The corpus epididymis collected at 4 months of age was subjected to evaluate expressional changes of Cx isoforms by quantitative real-time PCR. Treatment of low-dose EB resulted in increases of Cx32, Cx37, and Cx45 transcript levels, while exposure to high-dose EB decreased expression of Cx26, Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45. Treatments of Flu caused significant decreases of expression of all examined Cx isoforms, except Cx37 and Cx43 shown no expressional change with high-dose Flu treatment. These findings imply that expression of most Cx isoforms present in the corpus epididymis would be transcriptionally regulated by actions of androgen and/or estrogen during postnatal period. PMID- 27004264 TI - Production of Cloned Korean Native Pig by Somatic Cell Nuclear Transfer. AB - The Korean native pig (KNP) have been considered as animal models for animal biotechnology research because of their relatively small body size and their presumably highly inbred status due to the closed breeding program. However, little is reported about the use of KNP for animal biotechnology researches. This study was performed to establish the somatic cell nuclear transfer (SCNT) protocol for the production of swine leukocyte antigens (SLA) homotype-defined SCNT KNP. The ear fibroblast cells originated from KNP were cultured and used as donor cell. After thawing, the donor cells were cultured for 1 hour with 15 MUM roscovitine prior to the nuclear transfer. The numbers of reconstructed and parthenogenetic embryos transferred were 98 +/- 35.2 and 145 +/- 11.2, respectively. The pregnancy and delivery rate were 3/5 (60%) and 2/5 (40%). One healthy SLA homotype-defined SCNT KNP was successfully generated. The recipient based individual cloning efficiency ranged from 0.65 to 1.08%. Taken together, it can be postulated that the methodological establishment of the production of SLA homotype-defined cloned KNP can be applied to the generation of transgenic cloned KNP as model animals for human disease and xenotransplantation researches. PMID- 27004265 TI - Comparative Analysis of Morphometric Characteristics of Scorpaenidae and Gobioninae. AB - Measurements of closely related sets of classical and truss dimensions were analyzed to discriminate species of scorpaenidae including the dark banded rockfish, Sebastes inermis, the black rockfish, S. schlegeli, and gobioninae including the striped shiner, Pungtungia herzi, and the slender shiner, Pseudopungtungia tenuicorpa. The measurements of the dimensions were arc sin square root transformed, and compared as a function of the standard length of each species for statistical analysis. For values of the classical dimensions of the rockfish, 6 were greater for the dark banded rockfish than for the black rockfish, 1 value was smaller for the former, and for 2 values there was no statistically significant difference (P > 0.05). For values of the classical dimensions of the shiners, 9 values were greater for the striped shiner than for the slender shiner, 2 values were smaller for the former, and for 1 value there was no statistically significant difference (P > 0.01). For values of the truss dimensions of the rockfish, 6 were greater for the dark banded rockfish than for the black rockfish, 1 was smaller for the former, and for 4 values there was no statistically significant difference (P > 0.05). For values of the truss dimensions of the shiners, 13 values were greater for the striped shiner than for the slender shiner, 3 values were smaller for the former, and for 6 values there was no statistically significant difference (P > 0.01). The dimension sets used in this study may be useful as taxonomic indicators for discriminating among fish species in Korea. PMID- 27004266 TI - Effects of Starvation in Rock Bream, Oplegnathus fasciatus and Olive Flounder, Paralichthys olivaceus. AB - We assessed the effects of various dietary conditions on the growth, phenotypic traits, and morphometric dimensions of rock bream, Oplegnathus fasciatus and on the morphometric dimensions of sectioned olive flounder, Paralichthys olivaceus. Rock bream in the fed group increased in body weight, standard length, and condition factor, but these parameters decreased significantly for fish in the starved group (P < 0.05). The head connection dimensions of fish in the fed group decreased, while for starved fish there was increase in external morphometric dimensions (P < 0.05). In both species, sectioned morphometric analysis revealed that fish in the fed group had a larger body circumference and cross-cut sectional area, and greater cross-cut section height, relative to the starved group (P < 0.05). PMID- 27004267 TI - Legislation on Genetic Diagnosis: Comparison of South Korea and Germany: - With Focus on the Application and Communication Structure. AB - This article explores the questions regarding PND and PID, especially the concrete legal conditions for the justification of PND and PID. As such, the German law stipulating PND and PID in a very concrete and detailed manner is introduced and explained in comparison with the corresponding South Korean law. The South Korean Bioethics and Biosafety Act (BBA) stipulates various types of gene testing and does not demonstrate a delicate sense of each type of gene testing. In contrast to the South Korean regulation, in Germany, there exist specific regulations for genetic counseling. Especially in the case of PND, GEKO stipulates the process of genetic counseling very concretely, based on GenDG. In the case of PND and PID, it is important that the people concerned understand the meaning of testing in various angles, and restructuralize it by combining it with their own values as the diagnosis is directly combined with pregnancy/abortion, which influences the whole life of a woman (and her partner). In this context, the South Korean BBA needs to be amended as soon as possible. The sections on informed consent also need to be amended to make them more concrete. Furthermore, guidelines for concretizing the regulation of BBA need to be continuously formulated and developed. PMID- 27004268 TI - Effects of Feeder Cell Types on Culture of Mouse Embryonic Stem Cell In Vitro. AB - The suitable feeder cell layer is important for culture of embryonic stem (ES) cells. In this study, we investigated the effect of two kinds of the feeder cell, MEF cells and STO cells, layer to mouse ES (mES) cell culture for maintenance of stemness. We compare the colony formations, alkaline phosphatase (AP) activities, expression of pluripotency marker genes and proteins of D3 cell colonies cultured on MEF feeder cell layer (D3/MEF) or STO cell layers (D3/STO) compared to feeder free condition (D3/-) as a control group. Although there were no differences to colony formations and AP activities, interestingly, the transcripts level of pluripotency marker genes, Pou5f1 and Nanog were highly expressed in D3/MEF (79 and 93) than D3/STO (61and 77) or D3/- (65 and 81). Also, pluripotency marker proteins, NANOG and SOX-2, were more synthesized in D3/MEF (72.8+/-7.69 and 81.2+/-3.56) than D3/STO (32.0+/-4.30 and 56.0+/-4.90) or D3/- (55.0+/-4.64 and 62.0+/-6.20). These results suggest that MEF feeder cell layer is more suitable to mES cell culture. PMID- 27004269 TI - Comparison of Cell and Nuclear Size Difference between Diploid and Induced Triploid in Marine Medaka, Oryzias dancena. AB - The influence of triploidization on cell and nucleus size characteristics of the same tissues of erythrocyte, retina, kidney, hepatocyte and midgut epithelium in marine medaka, Oryzias dancena has been determined histologically. Induced triploid fish are produced by cold shock treatments. Likewise, the size of horizontal cell nucleus in inner nuclear layer of retina, ganglion cell nucleus in ganglion cell layer of retina, proximal tubule cell of kidney, hepatocytes and nuclear height of midgut epithelium all appear to be significantly larger than diploid (p<0.05). On the other hand, retina thickness is larger in diploid than induced triploid (p<0.05). Induced triploid shows low density of cell number. Results of this study suggest that same characteristics in the induced triploid exhibiting larger cells and nucleus sizes with fewer number of cells than the diploid can be useful criteria for the distinction between diploid and induced triploid, and also the ploidy level in marine medaka. PMID- 27004270 TI - Four Members of Heat Shock Protein 70 Family in Korean Rose Bitterling (Rhodeus uyekii). AB - Heat shock protein (HSP) 70, the highly conserved stress protein families, plays important roles in protecting cells against heat and other stresses in most animal species. In the present study, we identified and characterized four Hsp70 (RuHSP4, RuHSC70, RuHSP12A, RuGRP78) family proteins based on the expressed sequence tag (EST) analysis of the Korean rose bitterling R. uyekii cDNA library. The deduced RuHSP70 family has high amino acid identities of 72-99% with those of other species. Phylogenetic analysis revealed that RuHsp70 family clustered with fish groups (HSP4, HSC70, HSP12A, GRP78) proteins. Quantitative RT-PCR analysis showed the specific expression patterns of RuHsp70 family members in the early developmental stages and several tissues in Korean rose bitterling. The expression of 4 groups of Hsp70 family was detected in all tested tissue. Particularly, Hsp70 family of Korean rose bitterling is highly expressed in hepatopancreas and sexual gonad (testis and ovary). The expression of Hsp70 family was differentially regulated in accordance with early development stage of Rhodeus uyekii. PMID- 27004271 TI - Positive Effects of Diphlorethohydroxycarmalol (DPHC) on the Stability of the Integument Structure in Diet-Induced Obese Female Mice. AB - Diphlorethohydroxycarmalol (DPHC) is a known to modulate the expression of extracellular matrix (ECM) components in 3T3-L1. However, the possible role of DPHC in integument stability during obesity induction is not clear yet. We evaluated the effects of DPHC on collagen or elastic fiber quantity in integument during obesity induction with high-fat diet. The dorsal back integument sections were stained with hematoxylin-eosin, Masson trichrome, and Verhoff-Van Gieson. The intensities of collagen fibers and elastin fibers were analyzed with ImageJ. The number of fibroblasts was counted at *1,000 fields. The number of fibroblast was increased by obesity induction, but DPHC suppressed it in a concentrationdependent manner both in lean and obese mice. On the other hand, the intensities of collagen fibers were increased by DPHC treatment in obese mice groups but not in lean mice groups. The intensities of collagen fibers of obese mice were lower than that of the lean mice in 0% group. However, the number became similar between lean and obese mice by the treatment of DPHC. The intensity of elastic fibers was increased in the lean mice with the concentration of DPHC. In the obese mice group, there were increasing patterns but only significant at 10% DPHC group. The intensity of elastic fibers of obese mice was higher than lean mice in 0%, 1%, and 10% groups. Histologically epithelial cells and follicle cells which were diffused nuclear staining forms were increased by DPHC treatment. The results suggest that the activity of integument cells during obesity induction can be modulated by DPHC. PMID- 27004272 TI - Identification of Skeletal Deformities in Far Eastern Catfish, Silurus asotus under Indoor Aquaculture Condition. AB - For the 2 years of farming, at the indoor circulating aquaculture system, four kinds of skeletal deformities were found among 60 Far Eastern catfish, Silurus asotus. Deformities saw jawbone's luxation, abnormality of upper lip and malocclusion. Spinal deformity was most fatal deformities with low weight and small length. Jawbone's luxation had 1 maxilla and 2 mandibles. Abnormality of upper lip had just lip was back over. Malocclusion's left maxilla and right maxilla were not balanced. This experiment was any deformities in this species through the deformity can grasp how it affects. PMID- 27004273 TI - Differences and Variations among Anguilla japonica, Muraenesox cinereus and Conger myriaster from the Yellow Sea. AB - Genomic DNAs were extracted from the muscle of twenty-one specimens of three eel species collected in Anguilla japonica (AJ), Muraenesox cinereus (MC) and Conger myriaster (CM) from the Yellow Sea, respectively. In the present study, 7 oligonucleotides primers generated 191 specific loci in the AJ species, 226 in the (MC) species and 181 in the CM species, respectively. The primer BION-02 generated the most loci (a total of 83), with an average of 11.86 in the AJ species. The specific loci generated by oligonucleotides primers exhibited inter individual-specific characteristics, thus revealing DNA polymorphisms. With regard to average bandsharing value (BS) results, individuals from Conger myriaster species (0.808) exhibited higher bandsharing values than did individuals from Muraenesox cinereus species (0.729) (p<0.05). The longest genetic distance (0.430) displaying significant molecular difference was also between individual no. 01 within Anguilla japonica eel species and individual no. 04 within Anguilla japonica species. In this study, the dendrogram resulted from reliable seven oligonucleotides primers, indicating three genetic clusters composed of group I (ANGUILLA 01~ANGUILLA 07), group II (MURAENESOX 08~MURAENESOX 14) and group III (CONGER 15~CONGER 21). The existence of species differentiation and DNA polymorphisms among three eel species were detected by PCR analysis. As mentioned above, a dendrogram revealed close relationships between individual identities within three eel species. High levels of a significant genetic distance among three eel species showed this PCR approach is one of the most suitable tools for individuals and/or species biological DNA studies. PMID- 27004274 TI - Meniscal Root Tears: Identification and Repair. AB - Intact menisci are capable of converting the axial load of tibiofemoral contact into hoop stress that protects the knee joint. Total meniscectomy leads to rapid degeneration of the knee. Strong clinical and biomechanical data show meniscal root tears and avulsions are the functional equivalent of total meniscectomy. Lateral root tears commonly occur with knee ligament sprains and tears. Medial root tears are generally more chronic, and can be caused by preexisting knee arthritis. Meniscal root repair is indicated when there is identification of a meniscal root tear in a knee with minimal to no arthritis. Chronic root tears in the setting of osteoarthritis are treated conservatively. Meniscal root tears can acutely occur with cruciate ligament tears, can exaggerate symptoms of instability, and will have negative ramifications on outcomes of anterior cruciate ligament reconstruction if not addressed concomitantly. In this review, we describe the importance of the menisci for knee joint longevity through anatomy and biomechanics, the diagnostic workup, and ultimately a transosseous technique for repair of meniscal root tears and avulsions. PMID- 27004275 TI - Into the Paradigm of Local Factors as Contributors for Peri-implant Disease: Short Communication. AB - Although some systemic conditions have been associated with peri-implant disease, local contributing factors largely remain to be determined. This study aimed at evaluating, based on clinical photographs obtained from peri-implantitis treatment publications, the possible local contributing factors involved in its development based upon a survey obtained from three experienced clinicians (> 20 years of expertise). Cohen's kappa index was used to test the interexaminer reliability. "Too-buccal implant position" was the only parameter to reach almost perfect interexaminer agreement (kappa = 0.81). "Thin-tissue biotype" and "minimal presence of keratinized mucosa" demonstrated moderate agreement (kappa = 0.43 and kappa = 0.58, respectively). The rest of the parameters studied based on clinical photographs were fair or poor. Therefore, based on this clinicians' survey, implants too buccally placed, minimal or a lack of keratinized mucosa, and thin-tissue biotype might contribute to a higher susceptibility of developing peri-implantitis. These factors must be the focus of attention in future cross sectional studies on the incidence of peri-implant diseases. PMID- 27004276 TI - Bone Regeneration Potential of Biphasic Nanocalcium Phosphate with High Hydroxyapatite/Tricalcium Phosphate Ratios in Rabbit Calvarial Defects. AB - PURPOSE: This study aimed to evaluate the effect of biphasic calcium phosphate (BCP) with high hydroxyapatite/tricalcium phosphate (HA/TCP) ratios on bone formation in rabbit calvarial defects. MATERIALS AND METHODS: Sixteen New Zealand white rabbits were randomly divided into two groups, a control group and an experimental group. In each animal, bilateral circular defects (10-mm diameter) were created on the calvarium. In the control group (three rabbits per time frame), defects were grafted with autogenous bone chips in one side and left empty in the other side. In the experimental group (five rabbits per time frame), defects were grafted with BCP1 (HA:TCP, 8:2) in one side and BCP2 (HA:TCP, 9:1) in the contralateral side. The animals were sacrificed at 2 and 8 weeks as designated. Bone formation and residual grafting material were assessed by radiographic densitometry, microcomputed tomography (micro-CT), and histomorphometric analysis. RESULTS: Histologic observation revealed that BCP1, BCP2, and the autogenous bone group preserved good contours of the defect, while the unfilled defect group showed connective tissue healing. Micro-CT analysis at 8 weeks showed the comparable percentages of bone volume fraction (% BV/TV) of BCP1 (20.70% +/- 2.76%) and BCP2 (20.72% +/- 3.97%) and two times higher than that of 2 weeks (9.90% +/- 0.75%, 10.57% +/- 0.85%). The autogenous group had a significantly (P < .005) greater % BV/TV (34.58% +/- 8.85%) than other groups. The percentage of the material volume fraction of BCP1 and BCP2 was not different. The histomorphometry demonstrated a higher increase in newly formed bone from 2 to 8 weeks in all groups, and all were comparable (autogenous: 4.30% +/- 0.76%, 12.83% +/- 7.74%; unfilled: 2.82% +/- 1.19%, 8.14% +/- 6.35%; BCP1: 3.01% +/- 2.57%, 8.81% +/- 3.86%; BCP2: 3.24% +/- 1.09%, 10.27% +/- 3.98%). CONCLUSION: BCP with a high ratio of HA presented good osteoconductive properties and space-maintaining capacity and would be beneficial for long-term preservation or when stable graft volume is essential. PMID- 27004277 TI - Fracture Strength of Monolithic All-Ceramic Crowns on Titanium Implant Abutments. AB - PURPOSE: The fracture strengths of all-ceramic crowns cemented on titanium implant abutments may vary depending on crown materials and luting agents. The purpose of this study was to examine differences in fracture strength among crowns cemented on implant abutments using crowns made of seven different monolithic ceramic materials and five different luting agents. MATERIALS AND METHODS: In total, 525 crowns (75 each of Vita Mark II, feldspathic ceramic [FSC]; Ivoclar Empress CAD, leucite-reinforced glass ceramic [LrGC]; Ivoclar e.max CAD, lithium disilicate [LiDS]; Vita Suprinity, presintered zirconia reinforced lithium silicate ceramic [PSZirLS]; Vita Enamic, polymer-reinforced fine-structure feldspathic ceramic [PolyFSP], Lava Ultimate; resin nanoceramic [ResNC], Celtra Duo; fully crystallized zirconia-reinforced lithium silicate [FcZirLS]) were milled using a CAD/CAM system. The inner surfaces of the crowns were etched and silanized. Titanium implant abutments were fixed on implant analogs, and airborne-particle abrasion was used on their exterior specific adhesion surfaces (Al2O3, 50 MUm). Then, the abutments were degreased and silanized. The crowns were cemented on the implant abutments using five luting agents (Multilink Implant, Variolink II, RelyX Unicem, GC FujiCEM, Panavia 2.0). After thermocycling for 5,000 cycles (5 to 55 degrees C, 30 seconds dwell time), the crowns were subjected to fracture strength testing under static load using a universal testing machine. Statistical analyses were performed using analysis of variance (alpha = .0002) and the Bonferroni correction. RESULTS: No significant difference among the luting agents was found using the different all-ceramic materials. Ceramic materials LiDS, PSZirLS, PolyFSP, and ResNC showed significantly higher fracture strength values compared with FSC, FcZirLS, and LrGC. The PSZirLS especially showed significantly better results. CONCLUSION: Within the limitations of this study, fracture strength was not differentially affected by the various luting agents. However, the fracture strength was significantly higher for PSZirLS, PolyFSP, ResNC, and LiDS ceramics than for the FSP, LrGC, and the FcZirLS ceramic with all luting agents tested. PMID- 27004278 TI - Survival of Dental Implants Placed in Grafted and Nongrafted Bone: A Retrospective Study in a University Setting. AB - PURPOSE: To compare dental implant survival rates when placed in native bone and grafted sites. Additionally, risk factors associated with dental implant loss were identified. This study was based on the hypothesis that bone grafting has no effect on implant survival rates. MATERIALS AND METHODS: A retrospective chart review was conducted for patients receiving dental implants at the University of Texas, School of Dentistry from 1985 to 2012. Exclusion criteria included patients with genetic diseases, radiation and chemotherapy, or an age less than 18 years. To avoid misclassification bias, implants were excluded if bone grafts were only done at the same time of placement. Data on age, sex, tobacco use, diabetes, osteoporosis, anatomical location of the implant, implant length and width, bone graft, and professional maintenance were collected for analysis. RESULTS: A total of 1,222 patients with 2,729 implants were included. The cumulative survival rates at 5 and 10 years were 92% and 87% for implants placed in native bone and 90% and 79% for implants placed in grafted bone, respectively. The results from multivariate analysis (Cox regression) indicated no significant difference in survival between the two groups; having maintenance therapy after implant placement reduced the failure rate by 80% (P < .001), and using tobacco increased the failure rate by 2.6-fold (P = .001). CONCLUSION: There was no difference in the dental implant survival rate when implants were placed in native bone or bone-grafted sites. Smoking and lack of professional maintenance were significantly related to increased implant loss. PMID- 27004279 TI - Bone Regeneration with Bilayer Bone Augmentation Technique for the Treatment of Dehiscence-Type Defects Around Implants: A Preliminary Study in Dogs. AB - PURPOSE: The purpose of this study was to histomorphometrically compare the effects of the bilayer bone augmentation technique for the treatment of dehiscence-type defects around implants and evaluate the role as a membrane of the xenogeneic bone positioned as the outer layer in the bilayer bone augmentation technique. MATERIALS AND METHODS: Four standardized dehiscence defects measuring 5 mm in height from the crestal bone, 3 mm in width mesiodistally, and 4 mm in depth from the surface of the buccal bone were prepared on each mandible unilaterally in three dogs, and one implant was placed per defect, where each defect was treated with autograft, xenograft, the bilayer bone augmentation technique, or negative control without a membrane. The animals were sacrificed after an 8-week healing interval for histomorphometric analyses. The measurements of newly formed bone height, newly formed bone height contacting the implant, newly formed bone area, and the width of newly formed bone were made using incandescent and polarized light microscopy. RESULTS: Bone height and newly formed bone height contacting the implant in the autograft group were higher than in the xenograft, bilayer bone augmentation, and control groups. Newly formed bone area in the bilayer bone augmentation and autograft groups was higher than in the xenograft and control groups. The width of newly formed bone at 4.5 mm apically from the implant shoulder was greater in the xenograft and bilayer bone augmentation groups than in the control and autograft groups. However, the differences between the groups in bone height, newly formed bone height contacting the implant, newly formed bone area, and width of newly formed bone were not statistically significant in the histomorphometric examinations (P < .05). Data were verified with the Kruskal-Wallis test. CONCLUSION: The results of this study show the osteogenic effect of autogenous bone and the effect of mechanical support for prolonged space maintenance of xenogeneic bone for the treatment of dehiscence-type defects around implants. Further studies with a larger sample size are needed to confirm the efficacy of the bilayer bone augmentation technique. PMID- 27004280 TI - Conventional Versus Digital Impressions for "All-on-Four" Restorations. AB - PURPOSE: This study aimed to evaluate the most accurate impression technique for "All on Four" restoration, comparing conventional (CIG) and digital impressions (DIG). MATERIALS AND METHODS: Patients randomly selected for this study were required to be edentulous in at least one arch, presenting with severe posterior mandibular or maxillary atrophy. All patients underwent full-arch immediate-load rehabilitations, which were fixed to a total of four implants (two axial and two tilted). Following implant placement, patients were stratified into two groups. Conventional pick-up was carried out in the control group, and digital impressions were performed in the test group. Following prosthetic rehabilitation, patients underwent intraoral digital radiographs to check for the presence of voids at the bar-implant connection and to evaluate accuracy. Three-, 6-, and 12-month follow-up examinations were performed. RESULTS: A total of 25 patients received immediately loaded "All-on-Four" prostheses (17 maxillary, 13 mandibular) supported by four implants (total 120 implants), of which five received both maxillary and mandibular prosthetic rehabilitation (three patients in CIG, two patients in DIG). No implant dropouts occurred, showing a survival rate of 100%. The digital impression procedure required significantly less time than the conventional procedure (P < .001). CONCLUSION: Results demonstrate that it is possible to develop computer-aided design/computer-assisted manufacturing (CAD/CAM) cobalt-chromium full-arch rehabilitations with satisfactory accuracy using digital impression techniques. PMID- 27004281 TI - Reliability of Cone Beam Computed Tomography in Determining Mineralized Tissue in Augmented Sinuses. AB - PURPOSE: The aim of this study was to analyze cone beam computed tomography (CBCT) densitometries of maxillary sinuses augmented with human bone allograft. In addition, previously obtained microradiographic specimens were used to verify the diagnostic potential of CBCT. MATERIALS AND METHODS: A two-stage protocol was conducted in 21 consecutive patients, all with a crestal bone height < 2 mm. Mineralized human bone allograft particles were used to augment sinuses using a lateral window approach. A succession of CBCT scans of the maxilla were taken before surgery, immediately after sinus augmentation, and 6, 10, and 18 months after implant placement. Using virtual probes, CBCT images taken at 6, 8, and 10 mm from the crestal surface were processed with medical imaging software and expressed as gray level (GL). RESULTS: A total of 24 sinus augmentation procedures were performed in 21 patients. The average values of CBCT-GL ranged from 571 to 654, presenting the maximum value at 8 mm immediately after implant placement and the minimum value at 6 mm after 10 months. Furthermore, it was found that the graft mineral content decreased over time, completely disappearing between 10 and 11 months. CONCLUSION: CBCT and the medical imaging software employed for imaging visualization are reliable tools to study biomaterial behavior after sinus augmentation procedures. In addition, results from this study demonstrate that a complete resorption of human bone allograft is possible. Due to the limited sample size, further clinical and morphometric studies are needed. PMID- 27004282 TI - Bone Adaptation Induced by Non-Passively Fitting Implant Superstructures: A Randomized Clinical Trial. AB - PURPOSE: Passive fit of implant-supported restorations is difficult to achieve. The aim of this randomized clinical trial was to test the null hypotheses that a reduction in misfit strain does not occur over time, regardless of the initial strain level, and that changes in prosthesis-induced bone strain do not differ between restorations with two different levels of fit. MATERIALS AND METHODS: Twenty edentulous sites were restored with screw-retained fixed restorations on two implants either cast in one piece (misfit) or assembled by an intraoral bonding procedure (fit). The restorations had a bar-shaped pontic onto which a strain-gauged metal plate could be fixed. Repeated strain gauge measurements on patient-specific in vitro resin models and on the implants intraorally were performed every 4 weeks for a period of 6 months. Statistical analysis was based on Kruskal-Wallis tests, t tests, Welch two-sample t test (alpha = .05), and linear regression analysis. RESULTS: No reduction in misfit strain could be observed in vitro, indicating that alterations in prosthetic fit had not occurred in any restoration (Kruskal-Wallis; P > .05). Initial strain levels varied widely and differed significantly between fit and misfit restorations (t test; P = .0032). Regrouping the restorations with respect to a threshold strain level of 100 MUm/m resulted in 10 fit and 9 misfit restorations; 1 restoration had to be excluded from analysis due to a malfunctioning strain gauge. Seven fit restorations and five misfit restorations showed strain reduction in vivo based on linear regression, while percentage strain reduction did not differ between groups (Welch two-sample t test; P = .8186). CONCLUSION: Within the limitations of this randomized clinical trial characterized by an observation period of 6 months and only healthy subjects being enrolled, bone adaptation around statically and dynamically loaded implants occurred, causing a decrease in misfit strain evoked by non-passively fitting prostheses. For maintaining osseointegration of dental implants, passivity of fit of multiunit restorations seems not to be as critical as previously thought. PMID- 27004283 TI - Single-Tooth Implant Versus Three-Unit Fixed Partial Denture: A Study of Oral Health-Related Quality of Life. AB - PURPOSE: Many studies have investigated the impact of prosthetic treatment on oral health-related quality of life (OHRQoL). However, most of these have been performed among fully or partially edentulous patients. Studies involving patients with a single missing tooth are limited. The purpose of this study was to compare the OHRQoL between patients treated by single-tooth implants and three unit fixed partial dentures (FPDs) for single missing tooth restoration. MATERIALS AND METHODS: A cross-sectional survey was conducted in Korea with patients drawn by stratified purposive sampling based on age. OHRQoL was measured using the Korean version of the 14-item Oral Health Impact Profile (OHIP-14K) questionnaire. Pre- and posttreatment OHIP-14K scores were compared by paired t test. Single-tooth implants and three-unit FPDs were compared by two-sample t test. In addition, multiple regression analysis was used to evaluate the impact of treatment mode on OHIP-14K total score after adjusting the effect of demographics and clinical factors. RESULTS: Thirty-five patients with single tooth implants and 36 patients with three-unit FPDs were included. All participants had a significant improvement in OHRQoL compared with before the treatment (P < .0001). However, there was no statistically significant difference in the change of OHIP-14K score between the two treatment modes. In addition, the treatment mode had no significant impact on the change of OHIP-14K total score after adjusting the influence of covariates (P = .170). CONCLUSION: Both single tooth implants and three-unit FPDs for single missing tooth replacement resulted in significant and similar improvement of OHRQoL. PMID- 27004284 TI - Comparison of Clinical and Radiographic Outcomes of Platform-Switched Implants with a Rough Collar and Platform-Matched Implants with a Smooth Collar: A 1-Year Randomized Clinical Trial. AB - PURPOSE: The aim of this study was to evaluate and compare the clinical and radiographic outcomes of single implants with a platform-switched rough collar (PSRC) and a platform-matched smooth collar (PMSC). MATERIALS AND METHODS: Twenty six patients missing a tooth in the anterior maxilla (through the premolars) were randomly assigned to the PSRC or the PMSC group. All implants were placed in a flapless approach and restored with an early loading protocol. Clinical measurements were performed at surgery, loading, and at 3, 6, and 12 months after loading. In addition, radiographic evaluations were carried out using standardized periapical radiographs and cone beam computed tomography. Patient satisfaction surveys were completed, and microbial analysis with DNA probes was performed. RESULTS: The implant survival rate was 100% for both groups. The mean marginal bone level (MBL) was significantly higher in the PSRC group compared to the PMSC group at all time points. From the 2-week postoperative visit to 1 year postloading, the mean MBL change in the PSRC group was 0.21 +/- 0.56 mm and in the PMSC group it was 0.74 +/- 0.47 mm. Soft tissue profiles were stable over time, with no significant differences between groups. There were no significant differences between groups in the number of microbial species seen. Patients in both groups were highly satisfied with postoperative and postprosthetic experiences. CONCLUSION: In this study, the PSRC method preserved marginal bone by a mean of 0.53 mm more than the standard PMSC protocol. Within the limitations of the present study, it can be concluded that the PSRC protocol may be beneficial in marginal bone preservation. Longitudinal studies are needed to verify the long-term effects of this approach. PMID- 27004285 TI - Width of Keratinized Mucosa at Implant Sites in Patients Treated for Generalized Aggressive Periodontitis: A Cohort Study. AB - PURPOSE: The aim of this cohort study was to evaluate the width of keratinized mucosa at implant sites of partially edentulous patients who were treated for generalized aggressive periodontitis. MATERIALS AND METHODS: Dental implants were placed in 35 patients who were treated for generalized aggressive periodontitis and 18 periodontally healthy individuals (controls). At baseline, the keratinized mucosa of all implants was >= 2 mm. Follow-up examinations were conducted every 3 months over a 4-year period. RESULTS: The implant survival rate was 97.3% in patients with generalized aggressive periodontitis and 100% in the control group. Four years after implant insertion, patients with generalized aggressive periodontitis had significantly higher clinical attachment levels at the teeth and implants compared with the controls. At all time points, in both groups the mean probing depth at the implants was significantly larger than at the teeth. The mean widths of keratinized mucosa and keratinized gingiva were not significantly different between the two groups. In both groups, the widths of keratinized mucosa and keratinized gingiva were significantly higher at the maxilla than at the mandible. Four years after baseline, the implants in the mandible showed the smallest keratinized mucosa (mean: <= 1 mm). CONCLUSION: During the first 4 years after implant placement, no significant changes in the keratinized mucosa at implants could be shown, either in periodontally healthy patients or in patients treated for generalized aggressive periodontitis. The keratinized gingiva at the teeth was generally significantly wider than the keratinized mucosa at the implants. PMID- 27004286 TI - Relationship Between Long-Term Marginal Bone Loss and Bone Quality, Implant Width, and Surface. AB - PURPOSE: Short- or long-term implant survival and success are related to peri implant marginal bone loss (MBL), among other key factors. The purpose of this study was to analyze the role of clinical and implant-related variables in MBL over a long-term follow-up. MATERIALS AND METHODS: A retrospective study of 558 implants in 172 patients was conducted, analyzing the relationship between MBL and clinical, implant-related, and prosthetic design-related variables. MBL was measured on digital radiographs with specific software, using implant threads as reference. RESULTS: Linear mixed analysis revealed the following significant effects: a lower mean MBL for type IV bone (0.047 mm/year, 95% CI [-0.019, 0.119]) than for type III bone (0.086 mm/year, 95% CI [0.038, 0.138]), type II bone (0.112 mm/year, 95% CI [0.070, 0.167]), or type I bone (0.138 mm/year, 95% CI [0.052, 0.23]); an increased MBL of 0.033 mm/year for each increment of 1 mm in diameter (95% CI [0.002, 0.065]); a lower mean MBL in smooth implants (0.103 mm/year, 95% CI [0.090, 0.117]) vs rough implants (0.122 mm/year, 95% CI [0.102, 0.142]). The mean MBL was > 0 mm/year for all prostheses except for fixed complete dental prostheses. CONCLUSION: Within the limits of a retrospective follow-up study, a lower mean peri-implant MBL was associated with type IV bone, a smaller diameter, a smooth surface, and a fixed complete dental prosthesis. PMID- 27004287 TI - Bone Formation Following Sinus Augmentation with an Equine-Derived Bone Graft: A Retrospective Histologic and Histomorphometric Study with 36-Month Follow-up. AB - PURPOSE: The aim of this study was to investigate bone formation over time following maxillary sinus augmentation with an enzyme-deantigenic, bone collagen preserving equine bone graft by retrospective assessment of histomorphometric data. MATERIALS AND METHODS: Records of patients with atrophic ridges who underwent maxillary sinus augmentation with the enzyme-deantigenic equine bone graft and two-step implant placement between 3 and 12 months after the sinus augmentation surgery were assessed retrospectively. The histomorphometric data were clustered in three classes according to time of collection from the augmentation surgery and analyzed to assess newly formed bone deposition and residual biomaterial degradation rates. Data concerning the 36-month clinical follow-up were also assessed. RESULTS: Records of 77 patients and 115 biopsy specimens were retrieved, and histomorphometric data were clustered (3 to 5 months, n = 33; 6 to 8 months, n = 57; 9 to 12 months, n = 25). Mean minimum atrophic ridge thickness was 4.9 +/- 0.5 mm (range, 4.0 to 7.1 mm). The amount of newly formed bone and residual biomaterial did not significantly differ among the three clusters. Qualitative analysis showed a denser trabecular structure in late (> 8 months) samples. At the 36-month clinical follow-up, no differences were found among the implant success rates in the three groups, according to the Albrektsson and Zarb criteria for success. The overall implant success rate was 98.3%. CONCLUSION: Based upon this retrospective human study of 77 patients with 4 to 7 mm of residual bone, when enzyme-deantigenic equine bone is used for sinus augmentation, new bone formation occurs at an early time (< 3 months) after the grafting, and implant placement can be safely carried out as soon as 3 to 5 months after the augmentation surgery. PMID- 27004288 TI - A 3-Year Prospective Cohort Study on 132 Calcium Phosphate-Blasted Implants: Flap vs Flapless Technique. AB - PURPOSE: To evaluate the survival rate and marginal bone loss (MBL) of a calcium phosphate-blasted titanium implant inserted by a flap or flapless technique and to study the morphochemical characteristics of the implant surface. MATERIALS AND METHODS: Sixty out of 85 patients who received one or more implants were selected as eligible for this prospective longitudinal cohort clinical study. Titanium implants (n = 132) were placed in human healthy subjects using either a flap or flapless technique, selected on the basis of the best practice. The survival rate and MBL were evaluated after 3 months (preloading stress-free healing period) and after 6, 12, 24, and 36 months in relation to implant diameter, location, sex, and smoking habits. Surface morphochemical analyses were performed by environmental scanning electron microscopy connected with energy-dispersive x-ray (ESEM/EDX). RESULTS: The overall survival rate was 97.72%. After 3 and 36 months, MBL was 0.36 +/- 0.66 mm and 1.09 +/- 1.10 mm for the flapless group and 0.29 +/- 0.51 mm and 1.03 +/- 0.92 mm for the flap group. MBL showed a statistically significant increase with time (P = .0001), and differences were found at all times since 6 months. No statistical differences between the flapless and flap groups and sex were observed at any time, while MBL was significantly higher in the maxillary versus mandibular location (6, 12, and 24 months) and in smokers versus nonsmokers (6 months). Higher MBL in both groups was found for a smaller diameter (3.5 mm) than larger diameter (4.1, 5 mm). The surface showed a Ti-Al-V alloy displaying a uniform nanotexture. CONCLUSION: The implant system showed a high survival rate and markedly lower MBL considering the limits for acceptable progression. Flapless and flap techniques demonstrated similar results of MBL at the preloading healing period and at the 6 months to 3 years postloading periods. Both surgical procedures induced an early MBL during the preloading stress-free period. Implant diameter, mandibular/maxillary location, preloading stress-free period, and smoking habits affect MBL more than the type of surgery after both short- and long-term follow-up. PMID- 27004289 TI - Peri-implant Outcomes with Laser vs Nanosurface Treatment of Early Loaded Implant Retaining Mandibular Overdentures. AB - PURPOSE: To compare peri-implant changes seen with two early loading protocols for modifying surface treatment of dental implants-one modifying the collar portion (Laser-Lok implant) and the other modifying the implant surface (nanosurface-treated implant). MATERIALS AND METHODS: Thirty-six completely edentulous patients were chosen for this research. Conventional complete dentures were constructed for all patients. Two implants were used for each patient corresponding to mandibular canines. The patients were classified into two groups. Eighteen patients in group 1 received 36 laser-collar-treated implants; 18 patients in group 2 received 36 nanosurface-treated implants. The implants were early loaded 2 weeks after implant insertion. The peri-implant outcome was evaluated using the following variables: (1) modified Plaque Index, (2) modified Bleeding Index, (3) probing depth, (4) implant mobility using the Periotest instrument, and (5) marginal bone loss as recorded at the time of the overdenture insertion and 6 and 12 months after insertion. RESULTS: At all times of the study, the differences between the groups were not significant with regard to peri-implant tissue changes around implants. CONCLUSION: Both the laser collar- and nanosurface-treated dental implants showed the same peri-implant tissue changes with the early loading protocol. This study found that both early loading protocols are reliable, with good implant stability. PMID- 27004290 TI - Platelet-Rich Plasma Gel Combined with Bovine-Derived Xenograft for the Treatment of Dehiscence Around Immediately Placed Conventionally Loaded Dental Implants in Humans: Cone Beam Computed Tomography and Three-Dimensional Image Evaluation. AB - PURPOSE: This study clinically and radiographically investigated the potential of platelet-rich plasma (PRP) gel combined with bovine-derived xenograft to treat dehiscence defects around immediate dental implants. MATERIALS AND METHODS: This study was performed on 32 sites from 16 patients who each received an immediate implant for a single tooth replacement at a maxillary anterior or premolar site. Patients were divided into two groups according to the augmented materials used. One group received an immediate implant and filling of defects using a PRP gel plus bovine-derived xenograft. The other group received an immediate implant and filling of defects with a bovine-derived xenograft without PRP gel. Cone beam computed tomography (CBCT) was taken before placement, and at 6 and 12 months postsurgery. RESULTS: Both treatment procedures resulted in significant improvements for the primary outcome regarding bone fill, as well as the marginal bone level. In addition, statistically significant differences were found in the bone density for the combined therapy compared with sites treated with bovine derived xenografts alone (P <= .01). CONCLUSION: Autogenous PRP gel combined with bovine-derived xenograft demonstrated superiority to the bovine-derived xenograft alone, which suggested that it could be successfully applicable for the treatment of dehiscence around an immediate dental implant. Moreover, CBCT can be used to measure dehiscence and to assess bone thickness along the implant. PMID- 27004291 TI - The Use of Photofunctionalized Implants for Low or Extremely Low Primary Stability Cases. AB - PURPOSE: The objective of this study was to examine the success rate and development of implant stability of photofunctionalized implants with low and extremely low primary stability. MATERIALS AND METHODS: Primary implant stability was evaluated by measuring implant stability quotients (ISQs) at placement (initial ISQ). Of 301 consecutive implants placed over 2 years, 55 implants (in 38 patients) with initial ISQs less than 60 were included. All implants were photofunctionalized by chairside treatment with ultraviolet light for 15 minutes using a photo device immediately prior to placement, and the generation of superhydrophilicity and hemophilicity was confirmed. The rate of implant stability development was evaluated by calculating the osseointegration speed index (OSI), defined as the ISQ increase per month. RESULTS: Most of the 55 implants (90.9%) were in complex cases and placed in site-developmental sites with simultaneous or staged guided bone regeneration and/or sinus elevation or fresh extraction sites. The success rate was 98.2% after 2 to 3 years of follow up. The ISQ for all implants was 50.4 +/- 7.7 at placement and 74.3 +/- 5.7 at stage-two surgery (P < .001) after an average of 7.1 months of healing. All ISQ values were greater than 60 at the stage-two surgery. ISQ increases were inversely correlated with initial ISQ (R = 0.789) and resulted in consistently high ISQs at the stage-two surgery regardless of the degree of the initial ISQ. Implants with absent primary stability for which ISQ measurement was not possible at placement also attained ISQs of 75 or greater at the stage-two surgery. The OSIs of low initial stability (55 or lower) implants ranged from 3.9 to 4.7, which was considerably higher than the OSIs of as-received implants reported in the literature (0.36 to 2.8). CONCLUSION: Photofunctionalized implants placed with low, extremely low, or absent primary stability showed a high success rate, which was corroborated with a rapid increase in implant stability during the healing. Photofunctionalization was more effective for implants with lower primary stability, indicating that the technology was particularly effective in mitigating the challenging conditions. PMID- 27004292 TI - Marginal Bone Response Around Immediate- and Delayed-Loading Implants Supporting a Locator-Retained Mandibular Overdenture: A Randomized Controlled Study. AB - PURPOSE: Implant-supported mandibular overdentures (OVDs) have been proposed as the gold standard for the treatment of edentulous mandibles. There is limited evidence on the clinical outcomes of immediate loading of two unsplinted implants supporting a mandibular OVD. The purpose of this randomized controlled trial was to evaluate the performance of two unsplinted implants supporting a Locator retained mandibular OVD over 12 months loaded immediately or after a delay. MATERIALS AND METHODS: Each patient received two implants 4.0 mm in diameter and 8 to 15 mm long. Locator-retained mandibular OVDs were connected to the implants either immediately (IL) or 3 months postsurgery (DL). The primary response variable was radiographic bone loss (RBL) at 6 and 12 months postsurgery. Implant length, insertion torque, implant failure, prevalence of maintenance visits, and prosthetic complications were also recorded. RESULTS: Thirty participants (15 in the IL and 15 in the DL groups) were evaluated at 12 months. The implant cumulative survival rates were 100% and 93% for DL and IL, respectively. The mean RBL from baseline to 1 year was 0.54 (+/- 0.5) mm and 0.25 (+/- 0.5) mm for DL and IL, respectively. A statistically significant difference was observed at 12 months, with less RBL in the IL group. Insertion torque and implant length were not correlated with RBL. Also, no difference in frequency of maintenance visits and prosthetic complications was reported between the groups. CONCLUSION: Immediate loading of two unsplinted implants supporting a Locator-retained mandibular OVD seems to be a suitable treatment option. Significantly less RBL was observed after 1 year of loading around IL implants than around DL implants. Furthermore, neither implant length nor insertion torque seemed to affect RBL 1 year after surgical placement. PMID- 27004293 TI - Comparison of Initial Implant Stability of Implants Placed Using Bicortical Fixation, Indirect Sinus Elevation, and Unicortical Fixation. AB - PURPOSE: The aim of this study was to determine if self-threading dental implants placed using stopper drills to bicortically engage both the alveolar crest and sinus floor (bicortical fixation) achieved primary and/or secondary stability comparable to that of short implants only engaging alveolar crest cortical bone (unicortical fixation) or implants engaging both the crest and sinus floor but via greenstick fracture and grafting (indirect sinus elevation). MATERIALS AND METHODS: Thirty-eight patients exhibiting 7 to 11 mm of bone coronal to the sinus floor as confirmed by preoperative CBCT were recruited. Forty-five implants were randomly assigned to one of the placement techniques. No patient received more than two implants, which were placed in opposite sides of the maxilla while using different surgical techniques. An Osstell ISQ was employed immediately after implant placement to measure stability six times in a buccolingual dimension. Secondary stability was measured at stage-two surgery after a 3- to 6-month healing period. RESULTS: The greatest primary implant stability was achieved via indirect sinus elevation. However, no statistically significant difference was found among the three surgical techniques (P = .13; bicortical fixation: 71.4 [standard error = 2.1]), unicortical fixation: 69.6 [2.1], indirect sinus elevation: 75.9 [2.3]). The three techniques had similar secondary stability (P > .999; 79.9 [1.2], 80.0 [1.2], and 80.0 [1.3], respectively). Baseline residual ridge height measured on CBCT was similar (P = .1; 8.8, 9.9, and 9.4 mm, respectively), but implant diameter and length placed in the maxilla differed (P = .03/P < .001; 4.7/11.4 mm, 4.3/8.1 mm, and 4.7/11.8 mm, respectively). Primary implant stability was significantly correlated to CBCT bone density (r = 0.37). CONCLUSION: Primary and secondary implant stabilities of bicortical fixation did not differ significantly from those of unicortical fixation and indirect sinus elevation. However, use of the bicortical fixation technique is warranted since it is simpler and more economical than indirect sinus elevation; plus, it allows for longer implants than the unicortical fixation while yielding similar secondary implant stability. PMID- 27004295 TI - The Effect of Three Different Crown Heights and Two Different Bone Types on Implants Placed in the Posterior Maxilla: Three-Dimensional Finite Element Analysis. AB - PURPOSE: The purpose of this study was to determine the amount and localization of functional stresses in implants placed in two different bone types (type 3 and type 4) with three different crown heights in the atrophic posterior maxilla using finite element analysis. MATERIALS AND METHODS: A three-dimensional finite element model of the posterior maxilla was created from a computerized tomography image by using the Marc 2005 (MSC Software) program. Three different crown/implant ratios (1/1, 1.5/1, 2/1) in the first molar tooth zone were modeled. Type 3 and type 4 bone quality according to the classification system of Lekholm and Zarb was created. The total oblique force of 300 N with a 30-degree angle was applied from the locations of the mesiobuccal cusp (150 N) and the distobuccal cusp (150 N) of first molar teeth. RESULTS: For the implants, the highest stresses were observed around the implant neck at the crown/implant ratio of 2/1 (430.57 MPa). As the crown/implant ratio increased two times, the von Mises stresses increased at a rate of 47%. The highest tensile values exceeded the ultimate tensile strength of the cortical bone for all the designs. Also, the highest compressive values exceeded the ultimate compressive strength of the cortical bone in the 2/1 design for type 3 bone, and in the 1.5/1 and 2/1 designs for type 4 bone. As the crown/implant ratio increased from 1/1 to 2/1, the highest tensile value and the highest compressive value increased 13%. For the spongious bone, as the crown/implant ratio increased, the highest tensile value increased 42% and 85%, respectively. Tensile stresses increased at a rate of 26% in the 1/1 ratio, 30% in the 1.5/1 ratio, and 32% in the 2/1 ratio when the density of spongious bone decreased. Compression-related values also increased 34% in the 1/1 ratio, 35% in the 1.5/1 ratio, and 36% in the 2/1 ratio when the density of spongious bone decreased. CONCLUSION: Compressive and tensile stresses formed mostly at the alveolar bone around the implant neck that was cortical bone. Thus, it had to be preserved during the surgical procedures. Deformation due to the stresses had great importance for the type IV spongious bone due to the increase caused by the higher crown height levels. PMID- 27004294 TI - Evaluation of the Effect of Platelet-Released Growth Factor and Immediate Orthodontic Loading on the Removal Torque of Miniscrews. AB - PURPOSE: The purpose of this study was to evaluate the effect of platelet released growth factor (PRGF) and immediate orthodontic forces on the removal torque of miniscrews. MATERIALS AND METHODS: This study was conducted on three male dogs aged 6 to 8 months with a body weight of 17.6 to 18.4 kg. Sixty miniscrews were inserted in the posterior aspect of the femur. There were four groups, including loaded miniscrews with application of PRGF, unloaded miniscrews without application of PRGF, unloaded miniscrews with PRGF, and loaded miniscrews without PRGF. Twenty miniscrews were inserted in the femoral bone of one foot of each dog, including all the aforementioned subgroups. After 12 weeks, the miniscrews were removed by a removal torque tester device and measured in newton centimeters. RESULTS: The mean removal torque values in four groups of immediately loaded screws with PRGF, unloaded screws with PRGF, immediately loaded screws without PRGF, and unloaded screws without PRGF were 19.68, 21.74, 13.65, and 15.46 Ncm, respectively. It was shown that the mean removal torque value for the group with PRGF was significantly higher than that in the other groups (P = .0001). Although there was a tendency toward a decrease in removal torque value with immediate loading, it was not statistically significant (P = .21). CONCLUSION: According to the results of this study, applying PRGF with miniscrews increased their stability, but the delivery of immediate force on miniscrews had no effect on the miniscrews' stability. PMID- 27004296 TI - A Technique to Transfer the Emergence Profile Contours of a Provisional Implant Crown to the Definitive Impression. AB - This clinical report describes a method to create a proper emergence profile and accurately transfer it to the definitive impression, using an indirectly fabricated modified impression post. A provisional screwretained crown was indexed with a polyvinyl siloxane material. An autopolymerizing acrylic resin was used to modify an impression post on the polyvinyl siloxane index, which was then screwed onto the implant for the definitive impression after proper soft tissue healing. The indirectly fabricated modified impression post helped to transfer the contours to the definitive impression with minimal soft tissue irritation. PMID- 27004297 TI - Ectopic Implantation of Hydroxyapatite Xenograft Scaffold Loaded with Bone Marrow Aspirate Concentrate or Osteodifferentiated Bone Marrow Mesenchymal Stem Cells: A Pilot Study in Mice. AB - PURPOSE: To evaluate the influence of bone marrow cells in the bone formation in an ectopic subcutaneous model in mice. MATERIALS AND METHODS: Six BALB/c mice were divided into three groups of two each. In all groups, xenograft was implanted subcutaneously. In the negative control group, the xenograft was hydrated with saline solution. In the positive control group, the xenograft was embedded with osteodifferentiated adult mesenchymal stem cells derived from the bone marrow. In the experimental group, the xenograft was embedded with bone marrow aspirate concentrate. After 4 weeks, the animals were sacrificed and prepared for histologic, histomorphometric, and immunohistochemical analysis. The following tissues were evaluated: preosteoid tissue, loose connective tissue, and remaining xenograft particles. RESULTS: There was a statistically significant difference (P = .008) in the preosteoid tissue area between the negative control group (0 +/- 0%) and the other two groups, with 42 +/- 11% for the experimental group and 56 +/- 5% for the positive control group. Similarly, there was a statistically significant difference (P = .006) in the loose connective tissue area between the negative control group (49 +/- 18%) and the other two groups, with 3 +/- 9% for the experimental group and 0 +/- 0% for the positive control group. Regarding the xenograft area, there was not a statistically significant difference between the three groups (P = .143). CONCLUSION: The use of a mineralized scaffold loaded with either concentrated bone marrow aspirate or with osteogenically induced bone marrow mesenchymal stem cells favored the formation of osteoid tissue as opposed to the scaffold alone. PMID- 27004298 TI - Experimental Evaluation of the Effectiveness of Demineralized Bone Matrix and Collagenated Heterologous Bone Grafts Used Alone or in Combination with Platelet Rich Fibrin on Bone Healing in Sinus Floor Augmentation. AB - PURPOSE: The aim of this study was an experimental evaluation of the effectiveness of demineralized bone matrix (DBM) and collagenated heterologous bone graft (CHBG) used alone or in combination with platelet-rich fibrin on bone healing in sinus floor augmentation procedures. MATERIALS AND METHODS: In this study, 36 New Zealand rabbits were used. The bilateral sinus elevation was performed, and 72 defects were obtained. The rabbit maxillary sinuses were divided into four groups according to the augmentation biomaterials obtained: demineralized bone matrix (Grafton DBM Putty, Osteotech; DBM group), DBM combined with platelet-rich fibrin (PRF; DBM + PRF group), collagenated heterologous bone graft (CHBG; Apatos Mix, OsteoBiol, Tecnoss; CHBG group), CHBG combined with PRF (CHBG + PRF group). All groups were sacrificed at 2, 4, and 8 weeks after surgery for histologic, histomorphometric, and immunohistochemical analyses. RESULTS: The inflammatory reaction was moderate to intense at the second week in all groups and declined from 2 to 8 weeks. New bone formation was started at the second week and increased from 2 to 8 weeks in all groups. There was no significant difference in bone formation between the experimental groups that used PRF mixed graft material and control groups that used only graft material. The percentage of new bone formation showed a significant difference in DBM groups and DBM + PRF groups compared with other groups. There were osteoclasts around all the bone graft materials used, but the percentage of residual graft particles was significantly higher in CHBG groups and CHBG + PRF groups at the eighth week. CONCLUSION: There is no beneficial effect of the application of PRF in combination with demineralized bone matrix or collagenated heterologous bone graft on bone formation in sinus floor augmentation. The results of this study showed that both collagenated heterologous bone graft and demineralized bone matrix have osteoconductive properties, but demineralized bone matrix showed more bone formation than collagenated heterologous bone graft. PMID- 27004299 TI - Benefits of Allopurinol Treatment on Blood Pressure and Renal Function in Patients with Early Stage of Chronic Kidney Disease. AB - BACKGROUND: Hyperuricemia has been associated with increased risk of endothelial dysfunction, cardiovascular, and renal disease. Allopurinol is a potent xanthine oxidase inhibitor used in hyperuricemic patients. It has been shown to decrease cardiovascular disease and hypertension. However, studies have reported conflicting evidence on its effects on blood pressure (BP) and estimated glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients. OBJECTIVE: To demonstrate the effect of allopurinol on BP and estimated GFR in CKD patients. MATERIAL AND METHOD: Patients with CKD stage II-III were screened for possible study enrollment. All patients received allopurinol 50 mg once daily for 12 weeks. The main outcomes were to observe the changes of BP and GFR after given treatment. RESULTS: Forty-four patients were eligible with mean age of 70.14 +/- 8.50 years and mean estimated GFR of 43.22 +/- 14.44 mL/ min/1.73 m2. Serum uric acid decreased significantly from 8.11 +/- 2.68 to 7.05 +/- 2.38 mg/dL (p = 0.012) at the end of the study. Allopurinol had also statistically significant lower systolic BP (137.72 +/- 14.72 to 131.34 +/- 12.10 mmHg, p = 0.019) and diastolic BP (79.63 +/- 11.56 to 75.43 +/- 9.80 mmHg, p = 0.037) at 12 weeks when compared to baseline. There was significant increased in GFR after treatment (43.22 +/- 14.44 vs. 45.34 +/- 16.09, mL/min/1.73 m2, p = 0.029). No serious adverse effects were noted in any of the treated subjects. Two patients (4.5%) in the treatment group had minor skin reaction. CONCLUSION: The study results confirmed that 12 weeks of allopurinol treatment affects the values of serum uric acid, BP and GFR in early stage of CKD patients who already received standard antihypertensive agents without any significant serious adverse effects. PMID- 27004300 TI - The Effect of Food Avoidance in Adult Patients with Chronic Idiopathic Urticaria. AB - BACKGROUND: Recent findings show food allergy is rarely the cause of chronic urticaria. However; reports showed up to 5% of chronic idiopathic urticaria (CIU) was food induced urticaria (FIU) and the remission rate with food avoidance in CIU was varied. According to recent studies, skin prick test (SPT) is not a gold standard for investigating the culprit food allergen in CIU. The clinical response for food avoidance is still unclear. OBJECTIVE: The purpose of the present study is to investigate the association of food allergen and SP7 the clinical response after positive food avoidance in adult Thai patients with CIU. MATERIAL AND METHOD: We conducted a prospective study that included 76 patients, who presented with CIU at the Division of Dermatology, Department of Medicine, Phramongkutklao Hospital, between September 1, 2009 and May 31, 2010. Personal data, general physical examination, and detailed history were obtained. Twenty food allergens were used to perform SPT at the allergy clinic. The positive food allergens were enrolled to avoid the culprit food allergens for two to four weeks and evaluated the clinical response. RESULTS: Fifty-one of 76 patients (67.1%) gave history compatible with FIU. Shrimp (54.9%) and fish (49.0%) were the two most commonly suspected allergens by the patients. Fifteen of 76 patients (19.7%) had positive SPT In comparison to the SPT negative group in terms of clinical severity and effect on their daily lives, there was no significant difference. We then matched the SPT results with the patient's history. Five of 76 (6.6%) patients had results of SPT matching the patients' history. The five allergens in these patients were fish, milk, tomato, shrimp, and yeast. Fifty-one of 76 (67.1%) patients had negative SPT results but the patients suspected that certain foods were the cause of their urticaria. Fifteen of 76 (19.7%) patients had positive SPT results but the patients had never suspected any food allergen. Among these SPT positive patients, 13 food allergens were the culprits, the first three most common SPT allergens in this group were peanut, oyster and tomato. Upon SPT positive food avoidance, 12 of 15 (80%) SPT+ patients had significant improvement of symptom score in term of clinical severity and effect on their daily lives. CONCLUSION: Although SPT still yielded a low sensitivity for the diagnosis of FIU, the present study showed a very good response by food avoidance in patients who were SPT positive. PMID- 27004301 TI - The Effect of Vitamin D Supplementation on Metabolic Phenotypes in Thais with Prediabetes. AB - OBJECTIVE: To investigate the effects of vitamin D supplement for three months on anthropometric and glucose homeostatic measures in Thai adults with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). MATERIAL AND METHOD: Forty-seven IFG and/or IGT subjects enrolled in the study. Subjects were randomized into three groups, control (n = 18), vitamin D2 (20,000 IU weekly, n = 19) or vitamin D3 (15,000 IU weekly, n = 10). Anthropometric variables were obtained at baseline and at 3-month. Oral glucose tolerance test was performed at baseline and at 3-month. Total serum 25(OH)D, 25(OH)D3, and 25(OH)D2 were measured by LC-MS/MS. Insulin resistance (HOMA-IR) and insulin secretion index (HOMA%B) were calculated by the homeostasis model assessment. RESULTS: The total 25(OH)D levels significantly increased from baseline in both the vitamin D2 and the vitamin D3 groups, while there was no change in the control group. D3 supplementation raised 25(OH)D3 significantly (+13.7 +/- 4.9 ng/mL, p < 0.01) while D2 increased 25(OH)D2 levels (+25.9?4.2 ng/mL, p<0.001) but with a decrease in 25(OH)D3 (-13.1?3.1 ng/mL, p<0. 001). Subjects were classified into two groups, i.e., control (n = 18) and D2 or D3 supplementations (n = 29). After three months, waist circumference (WC) significantly decreased in subjects of vitamin D supplementation group. Body weight (BW p = 0.05), systolic blood pressure (SBP, p = 0.05), body mass index (BM, p = 0.06), and HOMA-IR (p = 0.09) also tended to decrease. Subjects with an increase of total 25(OH)D levels > 10 ng/mL (23 of 29 subjects) had significant decrease in HOMA-IR and increase in disposition index. Using robust regression analysis, we found the use of D3 was associated with a larger decrease in WC (coefficient = -3.5, p < 0.001) independent of the change in total 25(OH)D and baseline BMI. No difference between D2 and D3 was observed for other metabolic measures. CONCLUSION: Weekly supplementations of vitamin D2 (20,000 IU) or vitamin D3 (15,000 IU) improve metabolic phenotypes in subjects with prediabetes. D3 supplement may decrease waist circumference more than D2 supplement. PMID- 27004302 TI - Comparing Growth Rates after Hospital Discharge of Preterm Infants Fed with Either Post-Discharge Formula or High-Protein, Medium-Chain Triglyceride Containing Formula. AB - OBJECTIVE: To evaluate whether a high energy, high-protein, MCT-containing formula (HPMCT) is as appropriate as a post-discharge formula (PDF) for feeding preterm infants after hospital discharge by comparing growth, adverse effects, and cost per gram of bodyweight gain. MATERIAL AND METHOD: The present study was a randomized controlled trial. The calculated sample size was 20 infants for each intervention group. After the consent procedure, preterm infants who had postconceptional age (PCA) 35+1 to 36+0 weeks and weight between 1,800 and 3,000 g at hospital discharge were randomly enrolled to receive either PDF or HPMCT starting from the discharge day. Intervention period lasted at least 28 days and until the infant's weight was at least 3,000 g or PCA was at least 40+0 weeks. Body weight, length, and head circumference were measured on days 0, 14, 28, 56, and 84 after hospital discharge. Formula intakes and adverse symptoms (abdominal distension, diarrhea, and constipation) were recorded by parents before each visit in diaries provided by the study group. Cost was calculated from estimated actual formula intakes. RESULTS: There were six and five infants enrolled into PDF and HPMCT group, respectively. Demographic data were not different between the two groups. There were no significant differences of growth rates in both groups at days 28, 56, and 84 after hospital discharge. Adverse effects and costs were not different either. CONCLUSION: PDF and HPMCT might be comparably appropriate for feeding catching-up preterm infants after hospital discharge, as noted from growth rates, adverse effects, and costs. However, further studies involving biochemical and neurodevelopmental evaluation, with long-term follow-up in larger populations are needed to clearly compare both formulas. PMID- 27004303 TI - Target Controlled Infusion versus Sevoflurane/Desflurane Anesthesia for Laparoscopic Cholecystectomy: Comparison Postoperative Nausea/Vomiting and Extubation Time. AB - BACKGROUND: Target-controlled infusion (TCI) systems have been developed from manually controlled infusion systems and have rapidly increased in popularity, especially in laparoscopic surgery. Propofol is claimed to decrease nausea and vomiting. OBJECTIVE: To compare anesthetic techniques, propofol-TCI, desflurane, and sevoflurane, for better results in terms of postoperative nausea and vomiting (PONV) and extubation times. MATERIAL AND METHOD: The present study was prospective with informed consent from 75 patients, ASA 1-3 scheduled for laparoscopic cholecystectomy, and classified by anesthetic technique into three groups. The patients were induced by propofol target plasma concentration 6 ug/ml in Group P, or 1-2 mg/kg in Group S and Group D, fentanyl 2 ug/kg and vecuronium 0.1 mg/kg followed by propofol 2 to 5 ug/mI in group P, sevoflurane 0.5 to 3% in Group S, and desflurane 2 to 6% in Group D. RESULTS: The incidence of postoperative nausea and vomiting was least in Group P, both at the PACU (p < 0.001) and ward (p = 0.01). Extubation time excluding outlier were Group P 11.17 +/- 1.19 minutes, Group D 13.96 +/- 1.17 minutes, Group S 11.75 +/- 1.34 minutes (p = 0.25). There were no statistical differences in the amount of fentanyl (p = 0.38) and fluid replacements (p = 0.05). CONCLUSION: Laparoscopic cholecystectomy under propofol with TCI is one option of anesthetic technique with a significantly lower incidence of PONV compared with both sevoflurane and desflurane otherwise there is no statistical difference in the extubation time. Propofol-TCI technique is suggested for laparoscopic and ambulatory surgery. PMID- 27004304 TI - The Calibration of the Corneal Light Reflex to Estimate the Degree of an Angle of Deviation. AB - OBJECTIVE: To measure the conversion factor for the size of an angle of deviation from the clinical photographs of the corneal light reflex. MATERIAL AND METHOD: In this cross-sectional study, 19 normal subjects with 20/20 visual acuity were photographed with a digital camera while staring at targets placed five prism diopters (PD) apart from one another on a screen. The subjects were tested at a distance of 1 meter (m) and 4 m from a screen. Measurement of the corneal light reflex displacement for each fixed target was obtained from the photographs. The calibration of the corneal light reflex displacement in millimeters (mm) against the angle of deviation in PD was then analyzed with repeated measure linear regression analysis. RESULTS: At 1 m, the values of 0.047 mm/PD and 0.058 mm/PD were obtained as the conversion factor from reflex displacement to deviated angle for the nasal side and temporal side respectively. At 4 m, the values were 0.050 mm/PD and 0.064 mm/PD for the nasal side and the temporal side respectively. There were significant differences between the values obtained at the different distances, regardless of nasal or temporal side. CONCLUSION: Conversion factors were presented for estimating the strabismic angle at different distances and gazes. For clinical practice, the use of photographs to estimate the strabismic angle should use different values for different distances and strabismic types. PMID- 27004305 TI - Cross-Cultural Adaptation and Validation of the Voice Handicap Index into Thai. AB - BACKGROUND: The voice handicap index (VHI) is one of the most utilized instruments for measuring a patient's self-assessment of voice severity. The VHI has been translated into several languages, but not in Thai. OBJECTIVE: To examine the psychometric properties of a Thai translation of the voice Handicap Index (VHI) and assess the applicability in the screening diagnosis. MATERIAL AND METHOD: After receiving permission from the American Speech Language Hearing Association (ASHA), the original VHI had been translated and adapted to Thai by forward and backward standard translation. Eighty-five patients with voice disorders, divided in four groups according to the etiology of the diseases (neurogenic, structural, functional, and inflammatory), and 30 asymptomatic subjects were included in the present study. Internal consistency was analyzed through Cronbach's a coefficient. For the VHI test-retest reliability analysis, the Thai VHI was completed twice by 22 patients and assessed through the intraclass correlation coefficient. For clinical validity evaluation, the VHI scores from the pathological group were compared with the control group and compared among the four different pathological groups. The cutoff point for distinguishing the normal from the patient group was assessed by ROC analysis. Effects of age and gender on VHI scores were also evaluated. RESULTS: The Thai VHI showed a significant high internal consistency and test-retest reliability (Cronbach's alpha = 0.96 and r = 0.843, respectively). Mann-Whitney U test was used to compare the control group and pathological groups and revealed significant difference in total scores and its three domains scores (p < 0.001). ROC analysis demonstrated that a VHI score of 13 should be considered the threshold for revealing the impact of quality of life in voice disorder patients. Age and gender were not affect the VHI scores in both control and patient groups. CONCLUSION: The Thai VHI has high reliability and validity. The Thai version of VHI is considered to be a self-assessment tool for the severity of voice disorders in Thai patients. PMID- 27004306 TI - Surgical Outcomes of Sinonasal Inverted Papillomas in Songklanagarind Hospital. AB - OBJECTIVE: To evaluate the surgical outcomes and recurrence rate of inverted papillomas (IPs). MATERIAL AND METHOD: The medical records of patients diagnosed as IPs at Songklanagarind Hospital between January 2004 and December 2012 were retrospectively reviewed. Demographic data, clinical presentation, type of surgical approach, complications, and recurrence status were collected. RESULTS: From 64 patients, 75% were male. The average age was 55 years. IPs were classified in Krouse's classification system as followed: stage I = 6.3%, stage II = 21.9%, stage III = 70.3%, and stage IV = 1.5%. The surgical approaches were divided into endoscopic endonasal approach (EEA) 60.9%, EEA combined with external approach 35.9%, and external approach 3.2%. Complications such as synechea and maxillary sinus ostium stenosis occurred in 29.7% of patients. Thirty-seven point five percent had disease recurrence after surgery, most commonly at the frontal sinus 82.4%, and sphenoid sinus 60%. CONCLUSION: EEA is an effective treatment for IPs, especially in Krouse's classification stage I, II. The external approach combined with E A could be useful when the tumor extends to the anterolateral wall of the maxillary sinus. Finally, the surgeon must pay particular attention to the frontal and sphenoid sinus because of the high local recurrence rate. PMID- 27004307 TI - Correlation of FcgammaRIIIa Polymorphisms to the Response of Rituximab in Thai Patients with Diffuse Large B-Cell Lymphoma. AB - BACKGROUND: Rituximab is an anti-CD20 chimeric antibody widely used in combination with CHOP regimen for the treatment of diffuse large B-cell lymphoma (DLBCL). It is suggested that this antibody destroys B lymphoma cells mainly by antibody dependent cellular cytotoxicity (ADCC) mechanism via the binding of the drug to FC gamma IIIa receptor (FcgammaRIIIa) on natural killer (NK) cells, affected to kill cancer cells. The FcgammaRIIIa has genetic polymorphism at nucleotide position 559 (G559T or V158F or rs396991) have shown influence on the binding and efficacy of rituximab. OBJECTIVE: We identified the distribution of FcgammaRIIIa polymorphism in Thai patients with DLBCL and investigated the correlation between FcgammaRIIIa polymorphisms and the clinical outcomes in Thai DLBCL patients who were treated with rituximab plus CHOP chemotherapy regimen. MATERIAL AND METHOD: The Taqman SNP real-time PCR assay was used to identify the FcgammaRIIIa polymorphism in the present study and the clinical outcomes of these patients were evaluated and correlated between FcgammaRIIIa polymorphism. RESULTS: The distribution of FcgammaRIIIa genotype in patients were 54.17% homozygous V/V 10.41% homozygous F/F and 35.42% heterozygous V/F and there was no differences in clinical response among these patients (p-value = 0.31). Complete response was assessed in V/V 84.62%, V/F 88.24%, and F/F 80.00%. Partial response was in V/V 7.68% and F/F 20.00%. Stable disease was in V/F 11.76%, progressive disease in V/V 7.72%. CONCLUSION: The correlation could not be found between FcgammaRIIIa polymorphisms to the response of rituximab in Thai patients with diffuse large B-cell lymphoma. PMID- 27004308 TI - Association of Peripheral Autonomic Neuropathy and Sympathetic Skin Response in the Patients with Diabetic Polyneuropathy: A Pilot Study in Thailand. AB - OBJECTIVE: Investigate the association of peripheral autonomic neuropathy (PAN) symptoms and sympathetic skin response (SSR) in the patients with diabetic polyneuropathy (DPN) as a pilot study in Thai patients. MATERIAL AND METHOD: Sixty-eight DPN patients' limbs, conducted retrospectively between June 2012 and January 2014, were included and divided into two groups, 48 abnormal SSR limbs and 20 control limbs, respectively. All clinical data, demographic characteristics, PAN symptoms, and other associated factors were compared and analyzed. RESULTS: A comparison between abnormal and normal SSR groups in DPN limbs showed no significant differences of age, gender, body mass index (BMI), comorbidity of hypertension and dyslipidemia, duration of PAN symptoms, associated neurological signs of impaired light touch sensation, and muscle weakness or atrophy (p-value > 0.05). The PAN symptoms, either anhidrosis or hypohidrosis, and hyporemia showed significantly correlated to abnormal SSRs (p value = 0.003 and 0.028, respectively). Among symptoms of somatic small fiber neuropathy (SFN), burning paresthesia, and reduced thermal sensation revealed significantly correlated to abnormal SSRs (p-value = 0.032 and 0.021, respectively). Moreover, the study showed that history of fall in six months, history of foot ulcer in three months, impaired pinprick sensation, impaired proprioceptive sensation, decreased deep tendon reflex, burning paresthesia, reduced thermal sensation, either anhidrosis or hypohidrosis, and hyporemia had significantly associated with the occurrence of abnormal SSRs (p-value < 0.05). CONCLUSION: There was the association between PAN symptoms and abnormal SSRs in DPN patients' limbs. These data support the recent findings of several studies that abnormal SSR has the association with history of foot ulceration in diabetic patients. It warrants further investigation into the clinical utility of the SSR in diabetic patients. PMID- 27004309 TI - Efficacy and Safety of Single Botulinum Toxin Type A (Botox(r)) Injection for Relief of Upper Trapezius Myofascial Trigger Point: A Randomized, Double-Blind, Placebo-Controlled Study. AB - OBJECTIVE: Botulinum toxin injection has been applied for pain relief in various chronic pain syndromes. Recently, systematic review studies reported inconclusive effects of Botulinum toxin in myofascial pain management. The present study aimed to demonstrate the efficacy and safety of Botulinum toxin type A (BTxA) (Botox(r)) injection for pain reduction in myofascial trigger point (MTrP) of the upper trapezius muscle. MATERIAL AND METHOD: Thirty-three patients with 48 MTrP on the upper trapezius muscles over three months with moderate to severe pain intensity diagnosed at physical medicine and rehabilitation outpatient department were recruited between December 2011 and March 2012. Eligible patients were blinded and randomly injected with single 0.2 ml (20 IU) of BTxA for 24 MTrP and 0.2 ml of 0.9% NaCl solution for 24 MTrP at the most tender trigger point on the upper trapezius muscle. All patients were advised for stretching exercise and ergonomic adaptation throughout the study. At 3- and 6-week after injections, visual analogue scale (VAS), the pressure pain threshold (PPT), and reported adverse effects were measured. RESULTS: Both BTxA and control groups demonstrated statistically significant differences in VAS reduction and increased PPT after 3 weeks and 6 weeks compared with before treatment. There were no statistically significant differences in VAS reduction from baseline between the two groups at 3- and 6-week after treatment. A statistically significant difference in improvement of PPT from baseline and 6-week after BTxA injection compared with 0.9% NaCl group was shown (1.0 +/- 0.9 and 0.5 +/- 0.7, p = 0.036). There was mild degree side-effects that spontaneous resolved within one week in both groups without significant difference in percentage. No severe adverse effects were reported during the study. CONCLUSION: The efficacy in VAS reduction of a single 20 IU of Botulinum toxin type A (Botox(r)) injection was not different from 0.9% NaCl for myofascial trigger point at the upper trapezius muscle. However Botulinum toxin type A (Botox(r)) showed statistically significant more increased in pressure pain threshold at 6-week after injection without severe adverse effects. PMID- 27004310 TI - Factors Associated with Prosthetic Looseness in Lower Limb Amputees. AB - OBJECTIVE: To determine the factors associated with prosthetic looseness in lower limb amputees in Sisaket province. MATERIAL AND METHOD: The present was a cross sectional descriptive study. Subjects were lower limb amputees who previously obtained prostheses and required prosthetic replacements at the mobile prosthetic laboratory unit under the Prostheses Foundation of H.R.H. the Princess Mother at Khun Han Hospital, Sisaket province, in February 2013. Data including participant characteristics, prosthetic looseness data, and various variables were collected by direct semi-structured interview. Energy expenditures in physical activities were measured using the Thai version of the short format international physical activity questionnaire. Data between participants with and without prosthetic looseness were compared to determine prosthetic loosening associated factors. RESULTS: Among 101 participants enrolled, 33 (32.7%) had prosthetic looseness with average onset of 1.76 +/- 1.67 years. Diabetes mellitus was the only significant factor associated with prosthetic looseness from both univariate and multivariate analyses (HR = 7.05, p = 0.002 and HR = 5.93, p = 0.007 respectively). CONCLUSION: Among the lower limb amputees in Sisaket province, diabetes mellitus was the only factor associated with prosthetic looseness. Therefore, diabetic screening should be supplemented in lower limb amputee assessment protocol. In addition, we recommend that amputees with diabetes mellitus should receive prosthesis check out at approximately PMID- 27004311 TI - Work-Related Quality of Life among Medical Residents at a University Hospital in Northeastern Thailand. AB - OBJECTIVE: 1) To assess work-related quality of life (WRQOL) among medical residents at a university hospital in northeast Thailand. 2) To determine the strength of the association between personal and working condition components and WRQOL among medical residents. MATERIAL AND METHOD: A descriptive study was used to describe the WRQOL among medical residents. The study population comprised of all 375 residents affiliated with the university hospital. The Thai version of a self-administered work-related quality of life scale-2 was used for data collection. RESULTS: Testing the reliability revealed a Cronbach's alpha of 0.908. Questionnaires were completed by 259 of 375 (68.3%). The study found that the mean rating by residents for overall WRQOL was 113.8 out of 170 (SD 14.8). Most rated WRQOL as moderate (76.6%). The seven sub-factors were rated as moderate to high for employee engagement and control at work, moderate for home/work interface, general well-being and working conditions, high-moderate for job career satisfaction, and low-moderate for stress at work. Relationships between the personal and working condition components and WRQOL were analyzed using binary logistic regression. Residents in minor specialties had a higher WRQOL than those in major specialties (OR 2.522, 95% CI: 1.37, 4.63). Residents who had less than eight duty shifts/week had a higher WRQOL than those with more than eight duty shifts/week (OR 2.263, 95% CI: 1.16, 4.41). Similarly, residents working with less than 80 hours/week had a higher WRQOL than those working more than 80 hours/week (OR 2.344, 95% CI: 1.17, 4.72). A subgroup analyzes of those working in minor specialties showed the trend that working less than eight shifts/month and working less than 80 hours/week had the potential association with good quality of work-life (QWL). This phenomenon is presented in the subgroup analyses of those working in major specialties. Therefore, working hours and number of shifts might have played important role in contributing good QWL. CONCLUSION: To increase QWL, the residents and institutions should be better managed to have the appropriate number of working hours and to increase work-life balance, working condition, general well-being, and job-career satisfaction. On the other hand, stress at work must be reduced. PMID- 27004312 TI - Combination of Escitalopram and Rasagiline Induced Serotonin Syndrome: A Case Report and Review Literature. AB - BACKGROUND: Serotonin syndrome is a rare but potentially fatal complication of drugs that have effects on central nervous system serotonin. It is characterized by sudden onset of altered mental status, increased neuromuscular activity, and autonomic instability. CASE REPORT: The authors reported a case of serotonin syndrome associated with combined therapy of monoamine oxidase-B inhibitors and selective serotonin reuptake inhibitor A 77-year-old Thai man had been taking escitalopram for depression for three years. He presented with high-grade fever and confusion two days after taking rasagiline for Parkinson's disease. He also had agitation, hallucination, and behavioral change. Escitalopram and rasagiline were discontinued but his renal function worsened, turning to acute kidney injury. He was diagnosed as serotonin syndrome. CONCLUSION: This is the first case report of serotonin syndrome due to combination of escitalopram and rasagiline used. PMID- 27004313 TI - RUBELLA--SHOULD IT BE A PRIORITY IN THE NATIONAL IMMUNIZATION PROGRAMMES? AB - Rubella is a mild infection of childhood and young adults with 75% of cases occurring in age group 15-45 years. In unvaccinated populations, rubella usually occurs in spring with epidemics in 6-9 years cycles. Rubella has devastating effects on growing foetus if contracted by women in the first trimester of pregnancy. Perinatal infection of Rubella contributes to 2-3% of all congenital anomalies. Over the past three decades many resource risk countries have introduced universal or selective immunization programs against rubella with evidence that such interventions reduce the incidence of congenital rubella syndrome. In Pakistan the schedules of the Expanded Program on Immunization (EPI) do not include immunization against rubella and evidence is needed to estimate the risk of congenital rubella with a view to start immunization programmes to combat the menace of Congenital Rubella Syndrome (CRS). Logistically it is easy to add rubella vaccine to the already existing EPI schedules as measles is given on 9th and 15 month with little implications for cost, resulting in great reduction in CRS. PMID- 27004314 TI - OPTICAL COHERENCE TOMOGRAPHIC CHARACTERISTICS OF IDIOPATHIC CHOROIDAL NEOVASCULARISATION. AB - BACKGROUND: Idiopathic choroidal neovascularisation (ICNV) is the development of choroidal neovascularisation (CNV) in young adults without any apparent manifestations of primary ocular or systemic diseases We aim to assess characteristics and pathological changes at various stages in ICNV by optical coherence tomography (OCT). METHODS: We reviewed clinical charts of 40 ICNV eyes and classified them into three stages. Active stage < 1 month, intermediate 1-3 months and cicatricial > 3 months period after initiation of treatment in naive ICNV eyes. OCT characteristics of these morphological changes were determined. Parameters such as mean volume (MV), central macular thickness (CMT) and neovessels size (thickness and diameter) were analyzed and compared using one way ANOVA. RESULTS: We have 12 males and 28 females with a mean age of 30.1 +/- 7.80 years. In active stage, heterogenous activity of CNV was observed, along with disrupted RPE layer, surrounded by subretinal fluids and loss of foveal depression. In intermediate stage, CNV reflection appears homogenous with smooth peripheral Retinal pigment epithelium (RPE) lesion and reduction in retinal thickness. In cicatricial stage, OCT presents dome shaped elevation, strong homogenous reflection, absence of subretinal fluids and reformation of foveal depression. We have found that difference in mean volume and choroidal neovessels thickness was statistically significant in the three stages. CONCLUSIONS: In our study we have concluded that OCT is useful tool for following the clinical course of ICNV and understanding the pathological changes in CNV regression. PMID- 27004315 TI - GAIT PATTERN RECOGNITION IN CEREBRAL PALSY PATIENTS USING NEURAL NETWORK MODELLING. AB - BACKGROUND: Interpretation of gait data obtained from modern 3D gait analysis is a challenging and time consuming task. The aim of this study was to create neural network models which can recognise the gait patterns from pre- and post-treatment and the normal ones. Neural network is a method which works on the principle of learning from experience and then uses the obtained knowledge to predict the unknowns. METHODS: Twenty-eight patients with cerebral palsy were recruited as subjects whose gait was analysed in pre and post-treatment. A group of twenty-six normal subjects also participated in this study as control group. All subjects' gait was analysed using Vicon Nexus to obtain the gait parameters and kinetic and kinematic parameters of hip, knee and ankle joints in three planes of both limbs. The gait data was used as input to create neural network models. A total of approximately 300 trials were split into 70% and 30% to train and test the models, respectively. Different models were built using different parameters. The gait modes were categorised as three patterns, i.e., normal, pre- and post treatments. RESULTS: The results showed that the models using all parameters or using the joint angles and moments could predict the gait patterns with approximately 95% accuracy. Some of the models e.g., the models using joint power and moments, had lower rate in recognition of gait patterns with approximately 70 90% successful ratio. CONCLUSION: Neural network models can be used in clinical practice to recognise the gait pattern for cerebral palsy patients. PMID- 27004316 TI - CHANGES IN ORO-PHARYNGEAL AIRWAY DIMENSIONS AFTER TREATMENT WITH FUNCTIONAL APPLIANCE IN CLASS II SKELETAL PATTERN. AB - BACKGROUND: Functional appliances have been used since many decades for the correction of mandibular retrognathism. Similar oral appliances are a treatment modality for patients with Obstructive sleep apnoea. Hence, interception at the right age with these growth modification appliances might benefit a child from developing long-term respiratory insufficiency. Therefore, the purpose of our study was to assess the short-term effects of Twin block appliance (CTB) on pharyngeal airway size in subjects with skeletal Class-II pattern in a sample of Pakistani population. METHODS: A retrospective study was conducted from orthodontic records of 62 children (31 males, 31 females) with retrognathic mandibles using lateral cephalograms obtained at initial visit and after CTB treatment. Paired t-test was used to compare the pre-functional and post functional treatment airway size. Independent sample t-test was used for comparison between the genders and statistical significance was kept at <= 00.5. RESULTS: The upper airway width (p < 0.001), nasopharyngeal depth (p = 0.03) and upper airway thickness (p = 0.008) was substantially improved after CTB treatment. Males showed a greater increase in upper airway width (p = 0.03) and nasopharyngeal depth (p = 0.01) in comparison to the females. CONCLUSION: Functional appliance therapy can improve the narrow pharyngeal airway of growing children presenting with deficient mandibles having Class-II skeletal pattern. PMID- 27004317 TI - DIFFERENCES IN CULTURAL YIELD OF MYCOBACTERIUM TUBERCULOSIS ON MEDIA PREPARED USING COMMERCIAL AND HOUSEHOLD EGGS. AB - BACKGROUND: Mycobacterial culture is considered as the gold standard for TB diagnosis. It is performed on egg-based media using commercially available eggs to grow Mycobacteria from clinical samples. These eggs are known to contain high concentration of antibiotics, including fluoroquinolones, given to chicken to prevent early mortality. This study was performed to compare Mycobacterial growth on media prepared from commercial and antibiotic free household eggs. METHODS: Sputum samples from negative (No bacilli in 100 oil immersion field), scanty (1-9 AFB in 100 fields), 1+ (10-99 bacilli per field), 2+ (1-10 bacilli per field) and 3+ (>10 bacilli per field) were inoculated dually on Ogawa medium prepared from commercial and household eggs. Tubes were inspected every fourth day for the appearance of colonies till 60 days. Data tabulations and statistical analysis (F test for variation and unpaired Student's t test) were performed on Microsoft Excel. RESULTS: One microscopically negative sample showed growth on media prepared from household eggs, while all were negative on that prepared from commercial eggs. There were significant differences in time to culture positivity for samples graded 1+ (p = 0.02), 2+ (p = 0.002) and 3+ (p = 0.0003). CONCLUSION: Commercial eggs containing antibiotics can be a source of false negativity in cultures especially in microscopically negative samples. This can be of special concern in HIV patients who have high smear negativity. It is therefore important to either develop provision of antibiotic free eggs for media preparation or to develop and validate other laboratory investigations for smear negative TB patients. PMID- 27004318 TI - SEROPREVALENCE OF TOXOPLASMA GONDII INFECTION AMONG PATIENTS ADMITTED TO AL-ZAHRA HOSPITAL, ISFAHAN, IRAN. AB - BACKGROUND: Toxoplasma gondii (T. gondii) infection is one of the most common parasitic infections among humans and other warm-blooded animals worldwide. The aim of this study was to evaluate toxoplasmosis status in patients admitted to Al Zahra hospital, Isfahan, Iran. METHODS: This cross-sectional study was conducted from October 2012 to January 2015. During this period, 716 patients referred to AI-Zahra hospital in Isfahan city, Iran, were studied to investigate the IgG and IgM antibodies against T. gondii using ELISA kit. The data were analysed by Chi square and Fisher's exact tests. In addition, the relation of data with age and sex were also examined. RESULTS: Among 716 patients, 21 patients (2.9%) had positive IgM and 288 patients (40.2%) had positive IgG titer against T. gondii. Data analysis by Chi-square and Fisher's exact tests revealed that there was no significant relationship between IgG titer and age (p > 0.05). Additionally, there was no relationship between IgM titer and age (p > 0.05). The data showed that there was no relationship between IgG and IgM antibody titer and sex (p > 0.05). CONCLUSION: The prevalence of toxoplasmosis in Isfahan inhabitants seems fairly high but it can be concluded that the rate of seropositive patient is moderate comparing to other regions of country. Accordingly, the authors propose that all sensitive patients have to be tested for T. gondii antibody in order to prevent the consequences of disease. PMID- 27004319 TI - QUALITY OF LIFE AND FEAR OF FALLING AMONG AN AGING POPULATION IN SEMI RURAL, THAILAND. AB - BACKGROUND: Thailand is the country where large numbers of old population are living in rural areas. Multiple factors are influencing the health of old people but falling is the biggest cause affecting their quality of life. This study explores the relationship between the quality of life, and fear of fall among aging people in the semi-rural, Thailand. METHODS: A cross sectional study was conducted on 394 old aged individuals living in Nakornnayok Province. Participants were selected through simple random method (SRM) from village population list. Old people were interviewed by adapting World Health Organization quality of life instrument-older module (WHOQOL-OLD) to access the quality of life. Multiple logistic regression analysis was applied to identify factors associated with QOL. RESULTS: Above half of respondents during this study were female, married, educated with age 70.45 +/- 6.99. Majority of aging had low income and were not enrolled for their health check-up at hospitals on regular basis. Over a half of them suffered from chronic diseases, and one third of them were using instrumental aids such as visual glasses, walker support, wheel chair and hearing aids etc. Majority, (70%) of the participants was living in safe houses but (34%) reported fall at least one time in past year. Mean of fear of fall score (FFS) was calculated (26.97 +/- 4.31) and mean of FFS during using public transportation was (9.8756 +/- 2.19467). Two third of aging population reported the moderate quality of life (QOL). CONCLUSIONS: Study has concluded that the QOL in aging people is related with household safety and confidence to use public transportation. PMID- 27004320 TI - CLINICOPATHOLOGICAL FEATURES OF LIVER TUMOURS: A TEN-YEAR STUDY. AB - BACKGROUND: Various diseases affect the liver, among them, malignant and benign tumours with hepatic nodules are the most important. We aimed to evaluate the clinicopathological findings related to hepatic tumours and nodules. METHODS: This retrospective study was carried out during November 2014 to August 2015 by reviewing the hospital medical records of 164 registered patients with liver biopsies referred to Shahid Sadoughi educational General Hospital, Yazd, Iran, between 2004 and 2014. The samples were selected through the census method. Age, gender, clinical symptoms, initial clinical diagnosis, pathology reports and ultrasound results were considered as variables. Data were analysed by using SPSS 17. RESULTS: There were 87 (53%) men and 77 (47%) women. The mean ages of presentation for malignant and benign tumours were 57.9 +/- 17.2 and 44.9 +/- 19.4 years, respectively. Seventy benign tumours and 147 malignant tumours were recorded. The most frequent chief complaint was abdominal pain (54.9%) in both malignant (56.50%) and benign tumours (41.20%). Hepatocellular carcinoma (HCC) and hemangioma were the most prevalent malignant and benign hepatic tumours, respectively. In our study, correlation between pathology reports and primary diagnoses was 40.9%, and a significant relationship was found between sonography and pathological findings (p = 0.038). CONCLUSIONS: We found that only when primary clinical diagnosis and sonography were in favour of malignancy, they were correlated with pathology results. Clinicopathological assessments can help physicians in their diagnosis in order to facilitate the management of hepatic tumours. PMID- 27004321 TI - SUCCESS RATE OF OVERFILLED ROOT CANAL TREATMENT. AB - BACKGROUND: Traditionally, poor obturation has been considered the primary cause of root canal treatment failures. The purpose of this study was to assess the success rate of overfilled root canal treatment cases in order to decide whether a definitive restoration can be placed immediately following treatment in an overfilled case or whether the patient needs to be kept on a follow up prior to the placement of a definitive restoration. METHODS: A total of 1242 patient's periapical radiographs (1748 teeth) were assessed, out of which 397 teeth (in 285 patients) were found to be overfilled. Out of these 285 patients, 111 (128 cases) agreed to participate in this cross sectional study and were recalled for clinical and radiographic examination. Success was evaluated clinically by absence of symptoms (pain, swelling, tenderness to percussion and sinus tract) and radiograhically by the decrease in size of periapical lesion or no change in size. Increase in size of periapical lesion was deemed to be a failure. RESULTS: Our findings revealed that despite overfill, the treatment was successful in 115 cases and failure was noted in 13 cases showing an overall success rate of 89.8% and failure rate of 10.2%. Out of 13 cases of failure, all 13 showed an increase in periapical lesion size, out of which 10 were accompanied with pain. CONCLUSION: We have determined that there is no need to delay placement of a permanent restoration on overfilled teeth (ruling out the presence of other procedural errors) nor is there any need to pursue any further surgical or non surgical endodontic treatment. However we would suggest that patients should be kept on follow-up after placement of permanent restoration. PMID- 27004322 TI - TACROLIMUS DRUG LEVEL AND RESPONSE TO TREATMENT IN IDIOPATHIC CHILDHOOD STEROID RESISTANT NEPHROTIC SYNDROME. AB - BACKGROUND: The management of Steroid Resistant Nephrotic Syndrome (SRNS) is an uphill task for paediatric nephrologists as immunosuppressive agents are the mainstay of treatment in these patients. Tacrolimus is used along with steroids. This study is conducted to see the relationship between the tacrolimus dose, drug level and response in the management of SRNS. METHODS: This quasi experimental study was conducted at The Children's Hospital Lahore over a period of one year. Patients with SRNS of either sex and 1-10 years of age were included and those with secondary nephrotic syndrome were excluded. Tacrolimus was given at a dose of 0.05-0.1 mg/kg/day in 2 divided doses along with steroids. The follow-up was done for six months with proteinuria monitoring and tacrolimus drug levels done two weeks after initiation of treatment. RESULTS: Out of 42 patients, 27 (64.3%) were males and 15 (35.7%) were females. The most common histological diagnosis observed was mesangio-proliferative glomerulonephritis in 30 (71.4%) patients. The tacrolimus trough level range was 0.5-15.20 ng/ml with a mean value of 4.68 ng/ml +/- 2.85. Forty-one (97.6%) children showed complete response to treatment while one patient showed partial response. CONCLUSION: This study suggests that tacrolimus is an effective drug for treatment of SRNS in paediatric patients and there is no linear relationship between the drug dose, response and drug level. PMID- 27004323 TI - IN VITRO SUSCEPTIBILITY PATTERN OF EXTENDED SPECTRUM beta-LACTAMASE PRODUCING GRAM NEGATIVE BACILLI AGAINST TETRACYCLINES. AB - BACKGROUND: Extended Spectrum beta-lactamases (ESBLs) are emerging as common nosocomial pathogens and important cause of mortality and morbidity, if not treated properly. The need of the hour is to find effective treatment options for dealing with ESBL producing organisms. This study was aimed to evaluate in vitro susceptibility pattern of extended spectrum beta-lactamase producers against tetracyclines. METHODS: This descriptive cross-sectional study was carried out in the department of Microbiology, Army Medical College, Rawalpindi, National University of Sciences and Technology over a period of 6 months. Seventy eight non-duplicate isolates were included in the study. ESBL detection was done using Jarlier et al method. In vitro susceptibility of tetracyclines like tetracycline, doxycycline, minocycline and tigecycline was then tested using Modified Kirby Bauer disc diffusion method. The zones of inhibition were measured after completion of incubation period and interpreted as per CLSI and FDA guidelines. RESULTS: Approximately 56.4% of the isolates were Escherichia coli, 28.2% were Klebsiella pneumoniae, 10.26% were Enterobacter species, and 2.6% were each Klebsiella oxytoca and Acinetobacter species. ESBLs were found to be most sensitive to tigecycline, intermediate in susceptibility to minocycline while least sensitive to doxycycline and tetracycline. CONCLUSION: Among tetracyclines, tigecycline has best in vitro susceptibility against ESBL producing Gram negative rods. PMID- 27004324 TI - COMPARISON OF OPEN AND CLOSED TECHNIQUES OF HAEMORRHOIDECTOMY IN TERMS OF POST OPERATIVE COMPLICATIONS. AB - BACKGROUND: Haemorrhoids have been diagnosed and treated since the dawn of civilization, yet their cause, nature, symptomatology and especially their treatment options, remain hotly debated. The general principle however is that treatment should be directed by symptoms and the degree of haemorrhoids. The objective of the study is to compare early and late complications and wound healing time in open versus closed methods of haemorrhoidectomy. METHODS: This was a Randomized control trial conducted at Department of Surgery CMH Kharian for a period of 3 years. During the period of study, patients presenting in Surgical OPD (Age Range 20-72 Years) with 3rd or 4th degree haemorrhoids requiring haemorrhoidectomy (n = 364) were divided in two groups:--Group-1 was subjected to haemorrhoidectomy by open (Milligan-Morgan) technique and Group-2 underwent closed (Ferguson) haemorrhoidectomy. All patients were followed up for 2 months post-operatively and assessed for duration of wound healing and post-operative complications. RESULTS: In group-1 (Open haemorrhoidectomy) patients' ages ranged from 21-70 years with a mean age of 43 years (SD +/- 12.51). Duration of wound healing in this group was on the average 22 days (SD +/- 5.76). Incidence of early post-operative complications including haemorrhage, infection and urinary retention was 4.94%, 8.24% and 7.14% respectively. The only late complication observed was anal stenosis in one patient (0.55%). No fissure or faecal incontinence was observed in this group. In group-2 (subjected to closed haemorrhoidectomy), patients' ages ranged from 20-72 years with a mean age of 42 years (SD +/- 10.31). Duration of wound healing was on the average 14 days (SD +/ 3.25). Incidence of early post- operative complications, i.e., haemorrhage, infection and urinary retention was 2.19%, 7.69% and 2.75% respectively. No late complications (stenosis, fissure or incontinence) were observed in this group. CONCLUSION: There is no statistical significant difference between open and closed haemorrhoidectomy for the treatment of 3rd and 4th degree haemorrhoids in terms of wound healing time and post-operative complications. PMID- 27004325 TI - PRE-DONATION SCREENING OF VOLUNTEER PRISONER BLOOD DONORS FOR HEPATITIS B AND C IN PRISONS OF PUNJAB, PAKISTAN. AB - BACKGROUND: Prisoners as a high risk group are never recommended for blood donations. In Pakistan, prisoners are legally allowed to donate blood and get thirty days extra remission. Inspectorate of prisons allowed Alizaib Foundation for blood donation camps subject to predonation screening of volunteer prisoner blood donor against infectious diseases. This study was conducted to identify the potential benefits of pre-donation screening. METHODS: This cross sectional study was conducted in October, 2009 in Punjab. Intending volunteer prisoner blood donors from January, 2007 to September, 2009 from prisons of Punjab were included. Physically fit were tested for Hepatitis C Virus (HCV) and B Virus (HBV) by Rapid test kit before bleeding. Data was analysed by Epi-Info. RESULTS: A total of 5894 male volunteer prisoner donors were screened and 1038 (17.6%) were rejected. The mean age was 28 years (range: 17-70 years). Of 5894, 857 (14.5%) were HCV positive and 222 (3.8%) were HBV positive. HCV & HBV co infection was present among 41 (0.7%). Being convicted prisoner blood donor is significantly associated with higher seroprevalence for HCV (OR 1.35, 95% C.I. 1.17-1.57) and being under trial prisoner is significantly associated with higher seroprevalence for HBV (OR 1.40, 95% C.I. 1.06-1.85). CONCLUSION: Hepatitis B & C viruses were responsible for almost 18% prisoner blood donor rejection. Pre donation screening of blood donors is an effective intervention to improve the safety and limit the cost of blood. Treatment of identified cases may contribute to public health. In the international scenario this study findings necessitate the amendments in the relevant prison rules. PMID- 27004326 TI - RAISED INTRAOCULAR PRESSURE AND RECURRENCE OF RETINAL DETACHMENT AS COMPLICATIONS OF EXTERNAL RETINAL DETACHMENT SURGERY. AB - BACKGROUND: Patients with Rhegmatogenous retinal detachment may develop raised intraocular pressure and recurrence of retinal detachment when they undergo external retinal detachment surgery. The present study was conducted to determine the postoperative rise in intraocular pressure (IOP) and recurrence of retinal detachment. METHODS: The present descriptive study was conducted at Eye department of Lady Reading Hospital, Peshawar on 25 patients of both genders from August 2012 to July 2014. RESULTS: Of the 25 patients, 18 (72%) developed raised IOP in the immediate postoperative period; this figure decreased to 12 (48%) at one week. Following medical or surgical intervention in these 12 cases, there was only 1 (4%) case with mildly raised IOP at two weeks postoperative. Five (20%) cases developed recurrent retinal detachment which later resolved with treatment. There were no significant differences by age or gender. CONCLUSION: External Retinal Detachment Surgery raised intraocular pressure postoperatively and caused recurrence of retinal detachment. These complications were treated medically and surgically with resolution within two weeks. PMID- 27004327 TI - POSITIVE AND NEGATIVE PSYCHOLOGICAL CORRELATES, GENDER SPECIFIC AND TRADITIONAL FACTORS FOR FIRST ONSET ANGINA IN A SAMPLE OF PAKISTANI WOMEN. AB - BACKGROUND: Coronary Heart Disease (CHD) occurs to a greater extent in developed than developing countries like Pakistan. Our understanding of risk factors leading to this disease in women, are largely derived from studies carried out on samples obtained from developed countries. Since prevalence of CHD in Pakistan is growing, it seems pertinent to infer risk and protective factors prevalent within the Pakistani women. This case control study investigated the role of psychological, traditional and gender specific risk and protective factors for Angina in a sample of Pakistani women aged between 35-65 years. METHODS: Female patients admitted with first episode of Angina fulfilling the study inclusion/exclusion criteria were recruited within the first three days of stay in the hospital. One control per case matched on age was recruited. Translated versions of standardized tools: Life Orientation Test (LOT), The Hope Scale, Subjective Happiness Scale and Depression, Anxiety and Stress Scale (DASS) were used to measure the psychological variables. Information on medical conditions like diabetes, hypertension, family history of IHD, presence and absence of menopause and use of oral contraceptive pills was obtained from the participants. Body Mass Index for cases and controls was calculated separately with the help of height and weight recorded for the participants. RESULTS: Multivariate logistic regression analyses revealed that depression, anxiety and stress are risk factors, were as optimism and hope are protective predictors of Angina. 64% and 85% of variance in Angina were attributed to psychological factors. Menopause, diabetes and hypertension are significantly associated with the risk of Angina, explaining 37% and 49% of variance in Angina. The study provides evidence for implementation of gender specific risk assessment and preventive strategies for Angina. The study gives directions for large scale prospective, epidemiological, longitudinal as well as interventional studies, to be tailored for indigenous population and secondly development and standardization of measures to appraise psychological factors of Angina prevalent within the Pakistani population. PMID- 27004328 TI - CAN ULTRASOUND ABDOMEN HELP IN EARLY DIAGNOSIS OF DIABETES MELLITUS? AN OBSERVATIONAL STUDY. AB - BACKGROUND: Diabetes mellitus is a common disease. Similarly, ultrasound findings of fatty change and renal crystals are commonly seen on ultrasound. In the personal observation of the main author over the past so many years it was noticed that Diabetes Mellitus, Fatty liver and renal crystals all sit well together. This study tries to establish a relationship between diabetes mellitus renal echogenic foci and fatty liver. This study is first of its kind, as nobody has ever before investigated an association between the renal echogenic foci and fatty liver in relation to diabetes mellitus. METHODS: This cross-sectional, observational study was conducted at Radiology Department Combined Military Hospital, Kohat From 2nd June 2013 to 30th May 2014. Three hundred patients were collected on the basis of having fatty liver and renal echogenic foci on ultrasound and three hundred more patients were collected who had no fatty liver or renal echogenic foci on ultrasound. Their labs were done for diabetes mellitus. RESULTS: The patients having renal echogenic foci together with fatty liver had 83% positive rate of being diabetics, while patients with no fatty liver and no echogenic foci on ultrasonography had only 0.6% Positive rate of being diabetics. CONCLUSION: Our results provided the first demonstration of an association between renal echogenic foci together with fatty liver with the diabetes mellitus. Thus ultrasound examination of abdomen can be helpful in its early diagnosis if we make a protocol of doing fasting and random blood sugars in all those patients who have positive renal echogenic foci and fatty liver on their ultrasound examination. PMID- 27004329 TI - OUTCOMES IN CLOSED REAMED INTERLOCKING NAIL IN FRACTURES OF SHAFT OF FEMUR. AB - BACKGROUND: Femoral shaft fracture is one of the common fractures seen in accident and emergency department of our hospital. Violent forces are required to break this and strongest of human bones. There are various treatment modalities for femoral shaft fractures in adults like traction, brace, platting, intramedullary nail (IMN), external fixators and inter locking nails. The study was done with an objective to evaluate the results of closed reamed interlocking nail in fractures of shaft of femur. METHODS: A prospective study of 114 cases of femoral shaft fractures was carried out at orthopaedic unit of Ayub Teaching Hospital Abbottabad during 1 year. All these cases were treated with statically locked nails under spinal or general anaesthesia. These cases were followed up for up to one year and Results of the interlocking nail were observed in terms of union and complications. RESULTS: Out of 114 patients, 95 underwent union in 90 150 days with a mean of 110.68 days. Ten patients had dynamization within six weeks because of obvious fracture gap in radiograph. There were 3 patients who had non-union, and 6 patients had delayed union which was treated with dynamization. CONCLUSION: Close reamed interlocking intramedullary nail in femoral shaft fractures is the treatment of choice. Patient rehabilitation is early, hospitalization is short, and fracture healing response is good. PMID- 27004330 TI - EXPERIENCE AND OUTCOME OF VENTRICULAR-ATRIAL SHUNT: A MULTI CENTRE STUDY. AB - BACKGROUND: Ventriculoperitoneal (VP) shunt has been widely utilized in the treatment of hydrocephalus as a safe option but there is recent literature evidence that ventricularatrial (VA) shunt is not as notorious for its complications as proclaimed, to analyse and report our success with this procedure we conducted our study. METHODS: A total of 64 patients undergoing VA shunting were included in this case series study conducted at RMC and Allied hospital Rawalpindi. The data was collected over a period of 4 years from, 1st June 2010 to 1st June 2015. RESULT: Our study included 64 patients who underwent a VA shunt for hydrocephalus. Their age ranged from 25 to 75 years. Most of the patients were females (60%). The following complications were observed with 2 (3.12%) patients having blockage of the shunt at the neck, 3 (4.68%) suffered from glomerulonephritis, 2 (3.1%) had post-operative neck hematoma, 4 (6.25%) had wound infection, short lower end of the tube was found in 3 (4.68%), migrated lower end (into the subclavian) was seen in 1 (1.56%). Mortality was 1 (1.56%). These results were comparable to other studies. CONCLUSION: Neurosurgeons have been doing a VA shunt as a second procedure, after a VP shunt when the need due to a complication was encountered. We however share our experience regarding ventriculo-atrial shunting, as first choice procedure, because of its low incidence of shunt blockage unlike VP shunt, which has high rate of shunt blockage and therefore warrants repeated surgeries. PMID- 27004331 TI - PREDICTIVE PARAMETERS FOR SUCCESSFUL FUNCTIONAL MATURATION OF NATIVE ARTERIOVENOUS FISTULA. AB - BACKGROUND: Successful arteriovenous fistula (AVF) significantly reduces both the morbidity as well as mortality of the patients who have end stage renal disease, and significantly improve their survival rate. The objective of the study was to high light the role of various parameters in the functional maturation of arteriovenous fistula (AVF). METHODS: This descriptive analytical study conducted at Department of Vascular Surgery, Combined Military Hospital Lahore from January 2014 to January 2015. All consecutive patients who underwent creation of AVF and had pre and post-operative Duplex scan to assess the arteries and veins of the upper limbs, were included. The AVFs were created at wrist, forearm and arm under local anaesthesia. The data was collected from radiology department and dialysis centre and correlated with the data from operation theatre. RESULTS: A total of 127 patients (89 males and 38 females) were included in this study. Only 57.5% (n = 73) patients showed functional maturation of their AVFs. Of these, only 14 (36.8%) were females. Arterial and venous diameters of more than 2.5 mm (p = 0.0001 and 0.001 respectively), fistulae created at elbow (p = 0.001), presence of on-table thrill (p = 0.003), presence of on-table bruit (p = 0.001), patients having their AVFs created before the start of dialysis (p = 0.0037) and kidney transplant (p = 0.0042) were all positive predictors for successful functional maturation of AVFs. Female gender was a negative predictor and was responsible for non-maturation (p-value 0.003). CONCLUSION: Maturation of AVFs is a complex process influenced by a lot of factors. Although in our study various parameters proved to have positive impact on AVFs maturation, large prospective multi-centre studies are needed to provide well defined outcome. PMID- 27004332 TI - MEASLES IN VACCINATED CHILDREN 1.5 TO 3 YEARS OF AGE IN RURAL COMMUNITY OF DISTRICT PESHAWAR, PAKISTAN. AB - BACKGROUND: In many developing countries measles is a leading cause of childhood morbidity and mortality. Despite of vaccination thousands of children have been infected by measles virus during last couple of years in Pakistan. The objective of this study was to determine the measles vaccination coverage rate and frequency of measles among vaccinated children of age 1.5-3 years in rural community of district Peshawar. METHODS: The cross-sectional study was carried out among 385 children aged 1.5-3 year of rural community of Peshawar. After taking informed consent from parents/guardians a predesigned questionnaire was filled. Evidence of vaccination and measles history was taken by vaccination card, doctor prescription and parent/guardian recall. Data was gathered and analysed by using SPSS-16. RESULTS: Of the 385 children, 361 (93.7%) were vaccinated against measles at 9 month. It was found that 27 (7.48%) vaccinated children had measles history of which 23 (6.74%) were infected after 9 month vaccination. One hundred and ninety-two (49.8%) children were vaccinated both at 9 and 15 months, and 14 (7.29%) dual vaccinated children had a measles history, 9 among them (4.68%) were infected after taking both measles doses. CONCLUSION: The occurrence of measles among vaccinated children and low coverage rate of second dose of measles vaccine raises many questions about vaccination program and its efficacy. Further studies are needed to evaluate the influence of other predisposing factors like vaccine quality, manufacturer, supply, cold chain, handling, nutritional status of children and technical approach, on measles vaccine efficacy. PMID- 27004333 TI - RADIOLOGY EDUCATION: A PILOT STUDY TO ASSESS KNOWLEDGE OF MEDICAL STUDENTS REGARDING IMAGING IN TRAUMA. AB - BACKGROUND: Trauma remains one of the most frequent presentations in emergency departments. Imaging has established role in setting of acute trauma with ability to identify potentially fatal conditions. Adequate knowledge of health professionals regarding trauma imaging is vital for improved healthcare. In this work we try to assess knowledge of medical students regarding imaging in trauma as well as identify most effective way of imparting radiology education. METHOD: This cross-sectional pilot study was conducted at Aga Khan University Medical College & Khyber Girls Medical College, to assess knowledge of medical students regarding imaging protocols practiced in initial management of trauma patients. RESULTS: Only 40 & 20% respectively were able to identify radiographs included in trauma series. Very few had knowledge of correct indication for Focused abdominal sonography in trauma. Clinical radiology rotation was reported as best way of learning radiology. CONCLUSION: Change in curricula & restructuring of clinical radiology rotation structure is needed to improve knowledge regarding Trauma imaging. PMID- 27004334 TI - KNOWLEDGE, ATTITUDES AND PRACTICES OF HEPATITIS B AND C AMONG BARBERS OF URBAN AND RURAL AREAS OF RAWALPINDI AND ISLAMABAD. AB - BACKGROUND: Hepatitis B and Hepatitis C are serious global public health problems with a prevalence of 10-15% with majority of the cases seen in the developing countries including Pakistan. It is a blood borne infection transmitted by infected blood and blood products through transfusions, contaminated needles, vertical transmission, unsafe sex and reuse of razors by barbers. The literature search so far did not reveal any study comparing knowledge, attitude and practices of hepatitis B & C in barbers working in Urban and rural areas. METHODS: A comparative cross sectional survey was carried out among barbers of urban and rural areas of Rawalpindi and Islamabad. A structured close ended questionnaire was filled from total of 202 barbers by non-probability convenience sampling technique. Comparative data analysis was done including variables like age, education, knowledge about hepatitis B & C, mode of transmission, role of the blades and media etc. RESULTS: Knowledge about hepatitis B & C was good in urban areas (92%) as compared to those working in the rural areas (68%). Using new blade for every customer was seen in urban (100%) and rural (93%) area. However barbers knowledge about symptoms of the disease (urban 81% & rural 93%) and vaccination trend of Hepatitis B was low. CONCLUSION: This study showed a marked difference in the knowledge, attitude and practices of the barbers working in the urban and the rural areas. Main focus should be on launching Health education programs and behaviour change communication campaigns for the barbers. Strict regulatory monitoring must be done against unlicensed street barbers. PMID- 27004335 TI - LEARNING STYLE OF MEDICAL STUDENTS AND ITS CORRELATION WITH PREFERRED TEACHING METHODOLOGIES AND ACADEMIC ACHIEVEMENT. AB - BACKGROUND: Researchers have categorized the learning styles in many ways. Kolb proposed a classification of learner's styles as convergers, divergers, assimilators and accommodators. Honey and Mumford simplified learning styles as activists, reflectors, theorists and pragmatists. Neil Fleming's VARK model (Visual, Auditory, Read/write and Kinesthetic) is also popular. This study was carried out to determine the frequency of learning styles (Honey and Mumford) of medical students and its correlation with preferred teaching methodologies and academic achievements. METHODS: A total of 77 medical students of 4th year MBBS were selected through non-probability convenient sampling for this study. Honey and Mumford's learning style questionnaire, and a 2nd questionnaire to know their preference for different teaching methodologies were distributed to the students. Learning styles were identified and correlated with preferred teaching methodologies and academic achievements by Chi-square test. RESULTS: Mean age of the medical students was 22.75 +/- 1.05 years. Twenty one (27.3%) participants were males and 56 (72.7%) females. By learning styles, 7 (9.1%) medical students were activists, 36 (46.8%) reflectors, 13 (16.9%) theorists and 21 (27.3%) were pragmatists. Out of 77 students, 22 preferred interactive lectures; 16, small group discussion; 20 problem based learning, 10 preferred demonstration on models. Only 01 students preferred one-way lecture as the best teaching methodology. No significant correlation was found between learning styles and preferred teaching methodologies and learning styles and academic scores. CONCLUSION: Most of the medical students had reflector (46.8%) and pragmatist (27.3%) learning styles. Majority preferred interactive lectures (28.57%) and problem based learning (25.98%) as teaching methodologies. Aligning our instructional strategies with learning styles of the medical students will improve learning and academic performance. PMID- 27004336 TI - SOCIAL AND SOCIETAL BARRIERS IN UTILIZATION OF MATERNAL HEALTH CARE SERVICES IN RURAL PUNJAB, PAKISTAN. AB - BACKGROUND: The health status of pregnant women depends largely on the quality of the antenatal and delivery services available to them. Maternal mortality remains a major public health problem with antenatal and delivery care utilization remaining low in Pakistan. This study explores the perspectives of rural community members about the antenatal and delivery care services' utilization by the community. METHODS: A qualitative study was undertaken in the rural community of District Attock. Focus Group Discussions (FGD) were conducted with husbands, married women of child-bearing age with young children and mothers-in-law. Data was analysed manually using content analysis techniques. RESULTS: Majority of the respondents sought antenatal care (ANC) after 3-4 months. They further reported that home was the preferred place of delivery followed by the local "rural health centre". The preferred attendant for delivery was the local Dai (traditional birth attendant). Major limitations to accessing ANC and delivery services were lack of knowledge about ANC, long distance and high transport costs to health care facilities. People had strong beliefs on faith healers (Pirs) and insufficient knowledge about danger signs. Traditional and customary practice as taweez dhaga, saya, purdah, non-availability of health care providers, and lack of trust on young community midwives led to people favouring the home based package of services provided by traditional birth attendants (Dais). CONCLUSION: The findings of this study indicate that demand side barriers such as lack of knowledge regarding home based care, social barriers, financial constraint and non-acceptability of community midwives (CMW) because services offered by traditional birth attendants (TBA) were more accessible in terms of distance and cost are a major challenge affecting utilization. Efforts towards ensuring the utilization of ANC and delivery services should be targeted towards rural areas and the importance of skilled care should be emphasized. Women should be encouraged to utilize antenatal and delivery services. PMID- 27004337 TI - PREVALENCE OF REFRACTIVE ERRORS IN MADRASSA STUDENTS OF HARIPUR DISTRICT. AB - BACKGROUND: Visual impairment due to refractive errors is one of the most common problems among school-age children and is the second leading cause of treatable blindness. The Right to Sight, a global initiative launched by a coalition of non government organizations and the World Health Organization (WHO), aims to eliminate avoidable visual impairment and blindness at a global level. In order to achieve this goal it is important to know the prevalence of different refractive errors in a community. Children and teenagers are the most susceptible groups to be affected by refractive errors. So, this population needs to be screened for different types of refractive errors. The study was done with the objective to find the frequency of different types of refractive errors in students of madrassas between the ages of 5-20 years in Haripur. METHODS: This cross sectional study was done with 300 students between ages of 5-20 years in Madrassas of Haripur. The students were screened for refractive errors and the types of the errors were noted. After screening for refractive errors-the glasses were prescribed to the students. RESULTS: Myopia being 52.6% was the most frequent refractive error in students, followed by hyperopia 28.4% and astigmatism 19%. CONCLUSION: This study showed that myopia is an important problem in madrassa population. Females and males are almost equally affected. Spectacle correction of refractive errors is the cheapest and easy solution of this problem. PMID- 27004338 TI - EFFECTIVENESS OF COMMUNITY SERVICE MODEL FOR INCREASING ROUTINE IMMUNIZATION COVERAGE AT PRIMARY HEALTHCARE FACILITIES IN A RURAL DISTRICT OF PAKISTAN: A QUASI-EXPERIMENTAL STUDY. AB - BACKGROUND: In Pakistan Routine Immunization coverage has been reported to be significantly low due to multiple factors that results in high number of deaths in children under 5. This study was conducted to assess the effectiveness of integrating Community Services to improve Routine immunization coverage in rural district of Pakistan. METHODS: A quasi-experimental study with control and intervention arms was conducted in government Basic Health unit's catchment population of Panjgur by interviewing household head/Fathers. Total 234 household head including fathers were interviewed during this baseline survey. Community service model was used for to increase routine immunization coverage at catchment area of Basic Health unit (BHU) in intervention group while routine services were given in control BHU. RESULTS: 230 parents completed the questionnaire during the end line after three months of intervention. There were no significant differences found between two groups at baseline but after the intervention, there was statistically significance difference (< 0.05) between both group's knowledge and practices regarding routine immunization. Moreover, there was no statistically significant difference in control group reported (> 0.05) after the intervention period. Overall immunization status after intervention where fully immunization status in intervention group after intervention was 88.8% as compared to control group after intervention was 13.6% for partial immunization status in intervention group after intervention was 11.1% as compared to control group after intervention was 81.1 for the Non-Immunization status in intervention group after intervention was 0% as compared to control group after intervention was 5.1%. CONCLUSIONS: Community Service Model has significantly improved the Knowledge & Practices among households/parents of children under 5 in the intervention arm. PMID- 27004339 TI - PATTERN OF INJURIES SEEN IN MASS CASUALTIES IN TERRORIST ATTACKS IN BALUCHISTAN, PAKISTAN--A THREE YEARS EXPERIENCE. AB - BACKGROUND: As a front line state in war against terror, Pakistan has been a victim of terrorism, for the last many years & Baluchistan has been the hub of all such terror activities. The objective of this study was to determine the incidence and type of injuries in mass casualties in terrorist activities in Baluchistan. METHODS: The study was done by the review of the record of all patients of terrorist attacks who were admitted in Combined Military Hospital (CMH) Quetta from 27th Aug 2012 to 31st Jul 2015. The final injuries sustained by the victims were documented in the patient charts after repeated examination. The data was collected from these patient charts. Data was analysed using SPSS-21. Frequency & percentages of different injuries was calculated to determine the injury pattern. RESULTS: A total of 3034 patients reported to the hospital (n 3034), 2228 were admitted (73.4%). Out of the injured, 1720 (56.69%) were patients of multi system trauma, whereas 1314 (43.3%) had a single site injury. Out of these 537 patients had fractures of long bones (17.6%), those with head & spinal injuries with neurological deficit were 455 (14.9%), 266 had abdominal injuries requiring surgical intervention (8.7%), 75 (2.47%) had thoracic injuries were whereas 25 (0.82%) were vascular injuries, requiring emergent limb saving surgeries. Sex ratio was M/F=5.7: 1 Mean hospital stay was 6.31 days. CONCLUSION: Majority of the injured had multisystem injuries; therefore the hospital should have a well-trained multi-disciplinary team of surgeons. In addition to general surgery, the subspecialties' should include orthopaedics, vascular, thoracic and neurosurgery. PMID- 27004340 TI - EFFICACY OF ENDOSCOPIC TREATMENT FOR PRIMARY VESICOURETERIC REFLUX IN CHILDREN. AB - BACKGROUND: Vesicoureteral reflux (VUR) is a common anomaly affecting 1-3% of all children and 30-50% of those with urinary tract infection (UTI). In the past febrile vesicoureteric reflux on chronic antibiotic prophylaxis were treated by open surgery. Now a day's endoscopic injection of a bulking material has replaced open surgical procedure in cases of primary VUR. Our objective was to assess the efficacy of endoscopic treatment for primary vesico-ureteric reflux in children. METHODS: This was a descriptive case series. One hundred and five patients with either unilateral or bilateral VUR (181 ureters) underwent endoscopic treatment for primary VUR between January 2011 and January 2014. Children from 1 to 12 years of age with grade-II to IV reflux on preoperative voiding cystourethrogram (VCUG) were enrolled through consecutive non-probability sampling. Efficacy of treatment was evaluated at three months post injection by a standard VCUG. Ureters with no or grade-I reflux were considered successful treatment. RESULTS: Out of 105 patients 76 had bilateral while 29 had unilateral reflux. Mean age was 5.7 years (SD +/- .7). Among 181 refluxing ureters, 116 (64%) were free of reflux, while 49 (27%) showed down gradation and 16 (8.8%) showed no response to treatment on postoperative VCUG. CONCLUSION: Endoscopic treatment for VUR is a viable option for patients with primary VUR and may be considered in management of such cases. PMID- 27004341 TI - ORAL WHITE LESIONS--HISTOMORHOLOGICAL ASSESSMENT AND ASSOCIATED RISK FACTORS. AB - BACKGROUND: Oral white lesions constitute a major clinical problem in Pakistan and South Asian countries. The study was done with the objective to analyse oral white lesions histologically and clinically, and evaluate association between various risk factors in different ages, gender, ethnic groups, sites and sizes of the lesion. METHODS: A total of 80 patients presenting with oral white lesions were included in this cross-sectional study conducted at Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi. The biopsy sample was fixed in 10% formalin and after standardized processing, slides were prepared, stained by Hematoxylin and Eosin, with special stains when required. The histo-pathological diagnosis of lesion was recorded. Mean and standard deviation were calculated for quantitative variable. Frequency and percentages were calculated for qualitative variables. RESULTS: Out of total 80 patients 43 were females and 37 males. The mean age of cases was 47.92 years. Majority of the patients were between 30 +/- 39 years. Buccal mucosa was affected in majority of the cases (55%), followed by lateral border of tongue 17.5% and lip mucosa (8.8%). No risk factor had been observed in almost half of the patients. Histologically Lichen Planus was the most common lesion (32.5%), followed by chronic nonspecific inflammation in (22.5%), keratosis without dysplasia (10%), keratosis with dysplasia (8.8%), Pemphigus vulgaris (7.5%), fungal infestation (5%) and Squamous cell carcinoma (3.8%). CONCLUSION: Oral Lichen Planus was the most common oral white lesion in our set up, with buccal mucosa involved in majority of the cases. Association between histo-pathological diagnosis with age and gender was insignificant. However, significant association was observed between histopathological diagnosis and site. Among risk factors significant association was seen between snuff dippers and pan users. PMID- 27004342 TI - EXPLORING DEMOGRAPHICS AND OUTCOMES FOR SPINAL TUMOURS FOLLOWING SURGERY IN COMBINED MILITARY HOSPITAL, PESHAWAR. AB - BACKGROUND: Tumours of the spinal cord, spinal meninges and cauda equina are relatively rare and their spectrum has not been studied extensively in Khyber Pakhtun Khawa province. We describe here the cases of spinal tumours treated in our setup over a period of two years. METHODS: This Descriptive Case Series was carried out with of 80 patients operated in our centre from January 2013 to January 2015. The clinical presentation of these tumours as well as demographic findings was analysed. Patients who underwent surgery for their tumours were included in the study. Patients were selected for surgery depending on their radiological and clinical findings. Lesions that were suggestive of metastasis were biopsied and further care was shared between specialized departments depending on the primary source. RESULTS: Male to female ratio was 1.5:1. Most of the spinal tumours were secondary tumours while meningiomas were the most common primary tumours. Most commonly patients belonged to young age group A (below 30 years.) 32.5%. Most common presentation was with paraparesis (27.5%) and paralysis (25%). A majority of patients regained good neurological function and did not show signs of recurrence at 1 year follow up. CONCLUSION: Given the limited experience at our centre, we believe that a wide range of spinal tumours can be successfully treated provided that clinical end points are kept in mind and treatment is individualized. Frankel grading is useful to assess surgical outcome in the patients. PMID- 27004343 TI - ARE PULP SENSIBILITY TESTS STILL SENSIBLE? AB - BACKGROUND: Electric and thermal tests are the most commonly employed methods for the diagnosis of pulp health status. The objectives of our study are to assess the validity, yield and accuracy of cold and electric pulp tests in determining the vitality of teeth requiring endodontic treatment. METHODS: A cross sectional study was carried out at the Dental Clinic of Aga Khan University Hospital on 75 patients requiring endodontic treatment. Before commencement of endodontic treatment, a provisional diagnosis of pulp status was made using an electric pulp tester and cold test. The tooth was then labelled as either vital or necrotic. Then an access openings was made and tooth's actual pulp status (vital/necrotic) was determined by observing bleeding in the pulp chamber. The validity, yield and accuracy were calculated on the basis of these findings. RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of cold test were 84%, 88%, 93% and 73% respectively. The sensitivity & specificity of electric test were 82% and 88% respectively whereas the positive predictive value negative predictive value of electric test were 93% and 71% respectively. The accuracy of cold and electric pulp test was 85% and 84% respectively. CONCLUSION: Both cold test and EPT have similar sensitivity, specificity and accuracy values. Although vitality tests have a promising future in the diagnosis of pulp health status but within limitation of this study we found that sensibility tests have satisfactory validity and accuracy values to be used routinely prior to endodontic and restorative treatments especially when used in conjunction with one each other. PMID- 27004344 TI - FREQUENCY OF POST-OPERATIVE FAECAL INCONTINENCE IN PATIENTS WITH CLOSED AND OPEN INTERNAL ANAL SPHINCTEROTOMY. AB - BACKGROUND: Fissure in ano is one of the commonest benign and painful proctologic diseases causing considerable morbidity and reduction in quality of life. There are medical as well as surgical treatment options for anal fissure. The study was conducted to compare the frequency of postoperative faecal incontinence in patients with closed lateral internal anal sphincterotomy with von-greaves knife versus standard Park's operation (open method) for chronic anal fissure. METHODS: This was a randomized controlled trial (RCT) was conducted at the Department of Surgery, KVSS, S.I.T.E. Hospital, Karachi, for a period of six months from 13th February to 12th August 2011. Ninety four consecutive patients having chronic anal fissure were assigned through blocked randomization to groups A & B, with 47 patients in each group. Closed lateral internal anal sphincterotomy (CLIAS) via von-greaves knife was carried out in patients of group-A whereas patients of group-B were subjected to open internal anal sphincterotomy (OIAS) also known as Parks' procedure. Faecal incontinence was noted on the 5th post-operative day. Data was analysed using SPSS 16. RESULTS: There were 81 (86.2%) males and 13 (13.8%) females with male to female ratio being 6:1. Mean age was 38.38 mp +/- 14.56 years. Post-operative faecal incontinence in patients undergoing CLIAS was 4.3% while it was 21.3% in those undergoing OIAS with a p-value of 0.027. CLIAS with von-greaves knife is effective in reducing faecal incontinence on 5th postoperative day as compared to standard OIAS. CONCLUSION: CLIAS with von greaves knife is effective in reducing faecal incontinence on 5th postoperative day as compared to OIAS (Park's procedure). Therefore, this technique may be used in future regularly to treat chronic anal fissure for prevention of this morbidity. PMID- 27004345 TI - ASSOCIATION OF PLASMA HOMOCYSTEINE AND WHITE MATTER HYPODENSITIES IN A SAMPLE OF STROKE PATIENTS. AB - BACKGROUND: Studies of homocysteine in vascular disorders have yielded conflicting data. There are also differences based on various ethnicities and cultures. In this study, we have examined the homocysteine patterns in local stroke patients, so as to ascertain the homocysteine status in a sample of local population. Homocysteine-white matter hypodensities relationship in stroke is emerging, as an important aspect in stroke pathophysiology and is thought to have prognostic and therapeutic values. METHODS: We included 150 stroke patients who were diagnosed as having clinical stroke on the basis of history; physical examination and CT (Computerized Tomography) scan of brain. These patients were recruited from neurology and emergency wards of two public sector hospitals of Lahore. The presence or absence of white matter hypodensities were diagnosed after consultation with a radiologist. Blood samples were collected from the same stroke patients. RESULTS: We found a strong association between white matter hypodensities and total homocysteine in plasma of stroke patients p < 0.001. CONCLUSION: Homocysteine is a risk factor for white matter hypodensities in stroke patients in our study. PMID- 27004346 TI - EVALUATION OF MODEL FOR END-STAGE LIVER DISEASE SCORE CUT OFF VALUES IN PATIENTS WITH HEPATIC ENCEPHALOPATHY. AB - BACKGROUND: Model for End Stage Liver Disease (MELD) is scoring system used for prioritization of patients waiting liver transplantation. Patients with decompensated chronic liver disease (DCLD) with higher MELD score and hepatic encephalopathy (HE) have poor outcome. We planned to note association between short-term mortality and various cut-off values of at admission MELD score in HCV related DCLD patients presenting with HE. METHODS: In this descriptive case series, 208 Hepatitis C (HCV) related chronic liver disease (CLD) patients with HE were included. At admission serum bilirubin, creatinine and INR were sought to calculate MELD score. Patients who improved were discharged and kept under regular follow up. Outcome was categorized into alive or expired in 3 months after admission. Based on MELD score cut off values of > 15, > 20, > 25 and > 30, association with outcome was determined using Chi-square test. RESULTS: One hundred and six (51%) patients were female. Mean patient age was 55.3 +/- 10.6 years. Outcome wise, 128 (61.5%) were alive and 80 (38.5%) expired. Mean MELD score of expired was 22.17 +/- 9.14. 55 (51%) patients with MELD score >15, 44 (65.7%) patients with > 20, 30 (73.2%) patients with > 25, and 21 (72.5%) patients with > 30 expired. MELD score > 20 had strongest association with outcome, p value less than 0.01. CONCLUSION: At admission MELD score > 20 are most significantly associated with poor outcome in DCLD patients with HE. PMID- 27004347 TI - DEMOGRAPHICS OF TUBERCULOSIS IN DISTRICT MANSEHRA. AB - BACKGROUND: Tuberculosis is one of the leading causes of morbidity and mortality across the globe. Pakistan is one of the 22 high tuberculosis burden countries of the world sharing more than 80% of the global burden of tuberculosis. METHODS: This study was a retrospective case-based study that analyzed secondary data obtained from TB-03 form at the office of the District Tuberculosis Control Officer (DTO), Mansehra. Data was entered into SPSS-20 and analysed. RESULTS: A total of 625 patients with a mean age of 32.1 +/- 19.1 years were registered at the DTO office during the year 2013. Most of the patients were female (57%) as compared to males (43%). The most common treatment outcome was "treatment completed", recorded against 56% of the patients. The proportion of patients declared "cured" at the end of the treatment was 236 (37.8%). There were only 4 (0.64%) cases of treatment failure during 2013. CONCLUSION: Despite falling incidence of tuberculosis and mortality across the globe, tuberculosis is still a major determinant of disease in our society. Aggressive case detection and treatment is needed to manage this disease. PMID- 27004348 TI - KNOWLEDGE AWARENESS AND BEHAVIOUR OF NON-MEDICAL STUDENTS ABOUT CARDIOVASCULAR DISEASES. AB - BACKGROUND: Cardiovascular diseases is the leading cause of death worldwide, yet very little data is available assessing the awareness of the younger population of Pakistan. The purpose of this study was to evaluate the awareness, knowledge and the preventive measures taken to avoid the health issues related to cardiovascular diseases. METHODS: It was a community based cross sectional descriptive study to assess the awareness and behavior in young non medical students. A questionnaire was developed and survey was conducted on 300 non medical students enrolled in different universities of Pakistan. Data analysis was performed using SPSS-16. RESULTS: The sample consisted of 300 students aged between 16 and 32 years. 6.7% of the participants had history of blood pressure, 0.7% had diabetes, and 68.3% had a family history of cardiovascular diseases. 17.4% students were smokers. In the knowledge section, only 22% respondent scored above 20 out of 28 showing lack of knowledge. 42.7% participants were concerned about developing coronary artery diseases. 43.3% and 6.7% knew their blood pressure and cholesterol level respectively.33.3% and 41.7% regulate their dietary fat and salt intake respectively. CONCLUSION: Our study elucidates that cardiovascular diseases are not perceived as major risk by Non Medical Students. Lack of knowledge, physical inactivity, and high positive family history render the target population prone to cardiovascular diseases. The findings of study indicates the need for heart disease awareness campaigns for young population, to escalate the preventive actions and adoption of healthy lifestyles so as to lower the incidence of cardiovascular diseases in Pakistan. PMID- 27004349 TI - INVESTIGATION OF MEASLES OUTBREAK IN A DISTRICT OF BALOCHISTAN PROVINCE, PAKISTAN. AB - BACKGROUND: Measles is a communicable viral disease which is a major public health problem and a leading cause of morbidity and mortality in the developing countries including Pakistan with implications for outbreaks. An outbreak was reported from Ibrahim Khan Village of Manzari union council (UC), Pishin District by medical officer during polio campaign on 15th April 2014. A team was sent to investigate the outbreak and suggest control measures. METHODS: Rapid assessment of outbreak was done by collecting data from house-to-house from April 16th-20th, 2014. Case was defined as "a person of any age, resident of village Ibrahim Khan village with non-vesicular maculopapular rash and fever along with one of the symptoms of cough, coryza and conjunctivitis from April 4th-20th, 2014". Routine immunization (RI) was assessed through recall and immunization cards and BCG scars were checked. Line list was developed and data was analyzed. RESULTS: Fifty five cases (attack rate = 11.27%) including 4 deaths (Case Fatality Rates = 7.27%) were found. Mean age of children was 47 months (4-132 Months). Age-group 0 5 years was most affected (n = 48, 87.27%). Along-with maculopapular rash and fever. Other predominant symptoms were: coryza (n = 52, 95%), conjunctivitis (n = 51, 92%) and pneumonia (n = 42, 77%). RI status assessment showed that none of these children had been immunized. About 56.36% of the respondents were unaware about RI, 16.36% mentioned that vaccinator had not visited their homes, 14.54% reported that health facility is far away and 12.72% reported that even if they could get access to a health facility, the vaccines were not available. CONCLUSION: Functionalization of EPI centre, vaccinations of all children and mass education was strongly recommended. Surveillance system for vaccine preventable diseases (VPDs) should be strengthened to prevent such outbreaks. Outreach activity must be carried out regularly to reach scattered population. PMID- 27004350 TI - CANCERS AMONG CHILDREN AND ADOLESCENTS AT A CANCER HOSPITAL IN PAKISTAN. AB - BACKGROUND: The Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), is a tertiary care cancer centre, providing the best facilities in cancer diagnosis and treatment in the region. A record of the registered patients is being maintained in the hospital-based registry and the results are posted on its official website on a regular basis. METHODS: This is an epidemiologic review of cancer patients 0-19 years of age, reporting cancers recorded at SKMCH & RC) Lahore, Pakistan, from January 1, 2011 - December 31, 2012, in patients aged less than or equal to 19-years, belonging to Lahore district. It includes: i) those who had come to the Hospital laboratory for diagnosis only; ii) those who were diagnosed and registered for treatment at the Hospital; and iii) those who were not accepted for registration (regardless of the centre of diagnosis), as per Hospital policy, and subsequently went to other centres for treatment. The results were summarized by sex, 5-year age-group (0-4, 5-9, 10-14, and 15-19), and the International Classification of Childhood Cancers' (ICCC) diagnostic group. The annual Age-Standardized Incidence Rates (ASIR) were computed through the Segi World Standard (1960), per 100,000 population. RESULTS: New cancer cases: 669. ASIRs for common malignancies: among males-leukaemia and myelo proliferative/dysplastic disorders 2.1, lymphoma and reticuloendothelial neoplasms 1.8, CNS and miscellaneous intracranial/intraspinal tumours 1.1; among females-leukaemia and myelo-proliferative/dysplastic disorders 1.9, CNS and miscellaneous intracranial/intraspinal 0.8, and malignant bone tumours 0.6. CONCLUSION: The rates are low compared to the rates reported in the West. However, it has been estimated that over 80% of the paediatric cancer cases, diagnosed among Lahore residents, are being recorded by this institution alone. Accordingly, reviewing the statistics on a regular basis can be very important in evaluating trends in childhood cancers in Lahore and implementing cancer control programs in the region. PMID- 27004351 TI - NUTRITIONAL SUPPLEMENTS AND THEIR USE IN THE TREATMENT OF MALNUTRITION IN DEVELOPING COUNTRIES. AB - BACKGROUND: Despite the high global prevalence of malnutrition, it remains under treated, or undetected. The high energy nutritional supplements are usually prescribed to promote rapid weight gain. However, there is no consensus on the most effective way to treat mild to moderate malnutrition. METHODS: For identification of articles search engines of the databases OVID, MEDLINE, EMBASE and Pub med were used for papers published from 2003 to 2014 in English language. RESULTS: The total energy intake including the supplements is significantly improved. However, the rate of weight gain by the high energy nutritional supplements in moderately malnourished children is less than the expected weight gain. CONCLUSION: While assessing the impact of the supplementation on child nutritional status, other factors should also be taken into account, including appetite suppression, replacement of habitual food intake and compliance to the intervention. PMID- 27004353 TI - TESTICULAR LIPOMATOSIS IN COWDEN DISEASE. AB - Cowden disease is a genetic syndrome resulting in formation of multiple premalignant hamartomas in different parts of the body with classical radiological features. In this report a case of Testicular Lipomatosis as a result of Cowden disease resulting in primary infertility. PMID- 27004352 TI - EUGLYCEMIC DIABETIC KETOACIDOSIS AND SEVERE ACUTE KIDNEY INJURY SECONDARY TO OFF LABEL USE OF SODIUM GLUCOSE COTRANSPORTER-2 INHIBITOR IN A TYPE-1 DIABETIC PATIENT. AB - Sodium glucose Cotransporter-2 (SGLT2) inhibitors are a new class of drug approved for the treatment of type-2 diabetes; however they are also increasingly used off label in type-1 diabetic patients. SGLT2 Inhibitors work by increasing glucose excretion in urine. Euglycemic diabetic ketoacidosis (DKA) is potentially life threatening side effect as patients have normal glucose and minimal symptoms thus delaying diagnosis and treatment. Our case report highlights the risk of using SGLT2 inhibitors in type-1 diabetes and also supports the need for long term studies to define clear efficacy and complications of SGLT 2 inhibitors in both type-1 and type 2 diabetes mellitis. PMID- 27004354 TI - NAEVUS SEBACEOUS OF JADASSOHN'S OF EYELID. AB - Naevus Sebaceous of Jadassohn is a rarely seen hamartomatous lesion and is a fourth type of sebaceous gland tumour, in which sebaceous glands show nevoid character of growth composed partly or completely of sebaceous glands. A detailed research revealed that very little data is available; no case of this disorder has been reported as an isolated eye lid lesion. Majority of the published cases are associated with systemic involvement. We present here a case report of this rare disorder. A middle age female patient presented with a mass of left lower lid since childhood without any other ocular and systemic abnormality. Excision biopsy along with rotation flap surgery was done. Histopathological examination of the specimen revealed the diagnosis. To our best of knowledge this is a unique presentation of naevus sebaceous of Jadassohn on eye lid which has not been documented till yet anywhere. PMID- 27004355 TI - VON HIPPEL LINDAU SYNDROME AND SURVEILLANCE: A FIVE YEAR FOLLOW UP CASE REPORT. AB - Von Hipple Lindau disease is a rare genetic autosomal dominant disorder, characterized by formation of tumors and fluid-filled cysts (sacs) in multiple organs of the body, which also carry a potential for malignancy. We are reporting a case of a young 20 years old female who presented to our department with von Hipple Lindau disease. PMID- 27004356 TI - RARE CASE OF IDIOPATHIC GINGIVAL FIBROMATOSIS AFFECTING PRIMARY DENTITION. AB - Gingival fibromatosis (GF) is a rare condition with an estimated incidence of 1750,000 in autosomal dominant cases and is supposedly genetic in origin. Gingival fibromatosis (GF) may occur as an isolated finding (Idiopathic gingival fibromatosis or IGF) or in combination with additional clinical problems that is, giving rise to syndromic forms of the disease. It usually is triggered when permanent dentition starts to erupt and can cover crowns of the teeth. Gingival fibromatosis occasionally manifests at birth or affect primary dentition. This enlargement may cause mal-position and diastema. Surgical excision of excessive fibrous tissue is the only treatment but it recurs. We are presenting here a case of 5 year old patient presenting with severe idiopathic gingival fibromatosis covering crowns of primary teeth and causing functional impairment. PMID- 27004357 TI - ACINAR CELL CARCINOMA OF PANCREAS IN A CHILD: A RADIOLOGICAL PERSPECTIVE. AB - Acinar cell carcinoma is a rare tumour arising from pancreatic acinar cells. Typical radiological patterns associated with it may suggest the unusual diagnosis even before final confirmation by histopathology. We present a case of an 8 year old boy who presented to clinic with symptoms of abdominal pain without associated jaundice or vomiting. Imaging revealed an atypical mass arising from head of the pancreas. Histopathology confirmed the diagnosis of acinar cell carcinoma. An idea about atypical and rare pancreatic masses is necessary to help direct the diagnosis and guide the pathologist for suspecting atypical pathology. PMID- 27004358 TI - AUTOIMMUNE HYPOTHYROIDISM IN PATIENT WITH NEUROFIBROMATOSIS-1. AB - A 53 year old woman, diagnosed with Neurofibromatosis I with multiple neurfibromas over trunk, upper limb & lower limb, she had cafe au lait spots on her abdomen skin. She was admitted to the tertiary care setup with the complains of cold intolerance, numbness in the limbs, high blood pressure & constipation, patient also had complain of weight gain, lab revealed high TSH, low Free thyroid hormones & positive anti thyroglobulin antibodies. Case was diagnosed with autoimmune hypothyroidism. This is the first case reported with such association of these two diseases. PMID- 27004359 TI - MAGNESIUM SUPPLEMENTATION IN CYSTIC FIBROSIS; SAVING AN INFANT. AB - Hypo-magnesaemia is an under diagnosed condition in patients of cystic fibrosis. Here a case is reported of an imminent complete respiratory failure, which was avoided by the timely administration of Magnesium Sulphate. The case report is followed by a brief recent literature search about hypo magnesaemia and perioperative management of cystic fibrosis. PMID- 27004360 TI - CRYPTOCOCCAL MENINGITIS IN IMMUNOCOMPETENT PATIENT. AB - Cryptococcal meningitis (CM) is life threatening fungal infection of central nervous system (CNS). Although it is commonly associated with immunosuppression but rarely it can occur in immune competent patient. We report a case of 21 year old non HIV infected girl. Based on initial diagnoses of tuberculosis Bacillus meningitis (TBM), she was started on anti-tuberculosis treatment (ATT). However failure to respond to treatment prompted a quest for alternative diagnosis. A final Diagnosis of CM was confirmed on latex agglutination antigen detection on cerebrospinal fluid (CSF) analysis. The patient responded well to antifungal treatment. Initially diagnosis was missed due to common occurrence of tuberculosis infection in Pakistan and resemblance of its symptomatology and magnetic resonance imaging (MRI) findings with CNS cryptoccocal infection. PMID- 27004361 TI - 'TEST-NEGATIVE ANGELMAN SYNDROME' WITH THYROID DYSFUNCTION: A RARITY BUT A REALITY! AB - Angelman Syndrome (AS) is believed to be a complex neuro-developmental genetic disorder that is often described clinically by the presence of behavioural uniqueness and movement disorders; in addition to having developmental delay and speech impairment. Genetic factors have been linked to the syndrome's aetiology in 90% of cases, although in 10% cases, an unidentified genetic mechanism accounts for the classic phenotypic features of AS. Angelman Syndrome in general or with associated thyroid dysfunction, have never been reported from Pakistan. This is the first ever case report from Pakistan reporting a rare case of clinically diagnosed AS with associated thyroid dysfunction in the presence of normal molecular genetic testing (DNA methylation test and UBE3A gene sequencing). In future, clinicians should make efforts in documenting similar cases with associated clinical profiles from our part of the world, thereby contributing to the local and regional epidemiology of these syndromes. PMID- 27004362 TI - ISOLATED HYDATID DISEASE OF THE ILIAC BONE. AB - Hydatid disease of the bone usually is asymptomatic and is found as an accidental finding during unrelated imaging. However, they can become symptomatic due to enlargement and pressure effect or being infected by bacteria. Hydatid disease usually involves multiple organs (such as liver, lungs and brain). In our case, hydatid disease had involved bone and the patient presented only with a chronic hip pain without other symptom or sign. Here, a case of isolated ilium hydatidosis is reported. PMID- 27004363 TI - NEW BORN SCREENING IN PREVENTING CONGENITAL HYPOTHYROIDISM. AB - Congenital Hypothyroidism is one of the most common preventable causes of mental retardation which is highly prevalent in our society due to lack of a national neonatal screening program, lack of education of the parents, increased consanguinity, and lack of suspicion from doctor's leads to delayed diagnosis and an increased incidence of congenital hypothyroidism in our society. This Menace can be easily tackled with a mass neonatal screening program and effective legislation which would make sure that serious efforts are being made to eradicate this preventable disease from Pakistan. PMID- 27004364 TI - BURIED BUMPER SYNDROME. PMID- 27004365 TI - DIAPHRAGMATIC HERNIA. PMID- 27004366 TI - HYPOHIDROTIC ECTODERMAL DYSPLASIA. PMID- 27004367 TI - Extracellular alpha-synuclein--a possible initiator of inflammation in Parkinson's disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disease involving the loss of dopamine-producing neurons of the substantia nigra and the presence of Lewy bodies which contain high levels of alpha-synuclein. Although the causative factors of PD remain unclear, the progression of PD is accompanied by a highly localized inflammatory response mediated by reactive microglia. Recently, attention has focused on the relationship between alpha-synuclein and microglial activation. This review examines the role of alpha-synuclein on microglia in PD pathogenesis and progression, we also discuss the way of alpha-synuclein induced microglial activation. PMID- 27004368 TI - Scaling up nano-milling of poorly water soluble compounds using a rotation/revolution pulverizer. AB - We previously reported that a rotation/revolution pulverizer (NP-100) could mill a small amount of a drug (0.1 g) into nanoparticles in several minutes. In this investigation, scale up from the milligram to the kilogram scale of the nano milling process by the rotation/revolution pulverizer was studied. Phenytoin was used as a model drug with low solubility in water. After confirming the improvement of the phenytoin bioavailability by milling to nanoparticles using NP 100, scaling parameters were evaluated using NP-100 and the middle scale model of NP-100 (ARV-3000T). A theoretical equation for the specific collisional energy was adapted for wet milling; this suggested that the relative centrifugal acceleration of revolution (revolution G) and the drug concentration in the suspension were the two most important parameters. The results obtained using NP 100 and ARV-3000T correlated well when these two parameters were identical. These results were applied to the large scale model of NP-100 (ARV-10KT), where 2 kg (1 kg x 2) of phenytoin nanoparticles were obtained in 60 min. The results from PXRD and DSC indicated that the milled phenytoin by ARV-3000T and ARV-10KT maintained its crystallinity. These results suggest nano-milling using a rotation/revolution pulverizer will be widely applicable to the development of nano-medicine. PMID- 27004369 TI - A new device for efficient preparation of standard antibiotic bead chains and customized antibiotic delivery. AB - Antibiotic-loaded polymethylmethacrylate (PMMA) beads are widely used in orthopedic practice for the prevention of infections after open fractures and in the management of osteomyelitis. The use of commercial beads is limited by insufficient flexibility, lack of provision for selection of specific antibiotic, and short drug-release time. Further, the manual procedure for the preparation of PMMA beads is slow, and the products are not uniform in size. Uniformity of the bead size is crucial because the placement of oversized beads place at sites with limited space (e.g., narrow medullary canal) is difficult, and their retrieval from such sites is painful to the patient. To overcome the limitations of commercial beads and manually prepared beads, we developed a simple device for the efficient preparation of antibiotic-loaded PMMA beads of uniform sizes. We describe the device, bead preparation, and the characteristics of the beads prepared using our device, and the preliminary clinical results. The beads obtained using this device were relatively small, had excellent flexibility, and were suitable for implantation in small spaces. The device permits the selection of the antibiotic to be loaded on to the beads. The results of preliminary studies of the beads prepared using our device have been positive, highlighting the need for more large-scale and longitudinal investigations. PMID- 27004370 TI - Effect of cyclodextrins on the degradation rate of benzylpenicillin. AB - The effect of cyclodextrin (CD) inclusion complexes on the degradation of benzylpenicillin in aqueous solutions was investigated at several different pH values and 37 degrees C. The effects of neutral as well as both positively and negatively charged CDs were evaluated; all together 13 different CDs. Kinetic studies with HPbetaCD and RMbetaCD at pH ranging from 1.2 to 9.6 showed that CDs have stabilizing effect on the beta-lactam ring in aqueous acidic media but generally accelerated the hydrolytic cleavage of the beta-lactam ring in neutral and basic media. At physiologic pH (pH 7.4) quaternary ammonium CD derivatives (i.e., positively charged CD derivatives) have the highest catalytic effect, resulting in 6- to 18-fold enhancement of hydrolysis rate, while both the neutral methylated CDs had much less effect, resulting in 2- to 3-fold enhancement, and the negatively charged CD derivatives, resulting in only about 1.1- to 1.2-fold enhancement in the hydrolytic cleavage of the beta-lactam ring. Addition of water soluble polymers to the aqueous reaction media containing CDs was shown to decrease the catalyzing effects of CDs on the beta-lactam hydrolysis. PMID- 27004371 TI - Mini-tablet combination for sustained release of clonidine hydrochloride and hydrochlorothiazide: Preparation and pharmacokinetics in beagle dogs. AB - Mini-tablets are increasingly gaining attention in solid dosage form design as multiple-unit systems combining different active compounds and providing a single or combined pattern of modified release for polypharmacy or combined treatments. A combination therapy of clonidine hydrochloride and hydrochlorothiazide achieves effective blood pressure control and reduction in adverse effects. However, the combination formulation of immediate release must be taken several times a day, which causes noticeable fluctuation of blood pressure and inconveniences to the patients. The present study was performed to develop a mini-tablet combination for sustained release of clonidine hydrochloride and hydrochlorothiazide independently, in which the two drugs and fraction doses were formulated into separate mini-tablets with different release patterns. The mini-tablets were prepared by a direct compression method followed by filling into capsules and the factors that affected drug release were addressed. Further, studies of the pharmacokinetics were performed in beagle dogs. Finally, in vivo-in vitro correlations of the sustained release systems and bioequivalence with conventional preparations were evaluated. The mini-tablet combination released the two drugs over 24h in vivo with a steady plasma concentration, a markedly lower Cmax, extended Tmax and better bioavailability. In conclusion, sustained releases of the two drugs were obtained with this mini-tablet combination, which offers a feasible formulation and promising development value for hypertensive patients who need long-term therapy. PMID- 27004372 TI - MiR-301a is involved in adipocyte dysfunction during obesity-related inflammation via suppression of PPARgamma. AB - The present study explored the involvement and role of miR-301a in the adipose tissues. For the first time we identified the expression of miR-301a in the white adipose tissues of mice. A decreased level of miR-301a was correlated to increased chronic inflammation in the 3T3-L1 cells and circula- tion in an obese mouse model. Mechanistically, we demonstrated that miR-301a attenuated saturated free fatty acid-induced activation of peroxisome proliferator-activated receptor gamma (PPARy) and production of proinflammatory cytokines in 3T3-L1 cells. Target gene reporter assays showed that miR-301a directly targeted the 3'-untranslated region (3'UTR) of PPARgamma, resulting in a decrease of PPARy protein expression. The miR-301a inhibition of adipocyte differentiation was reversed by PPARgamma overexpression. PMID- 27004373 TI - Inhibitory effect of puerarin on vascular smooth muscle cells proliferation induced by oxidised low-density lipoprotein via suppressing ERK 1/2 phosphorylation and PCNA expression. AB - Puerarin, an isoflavonoid isolated from the traditional Chinese herbal medicine Pueraria lobata (Wild.) Ohwi, has been shown to process antioxidant, anti inflammatory, anti-cancer, anti-hypercholesterolemic, and anti-hyperglycemic activities in vivo and in vitro. The aim of the present study was to investigate the antiproliferative effects and the possible mechanisms of puerarin in vascular smooth muscle cells (VSMCs) stimulated with oxidised low-density lipoprotein (ox LDL). VSMCs were cultured and pretreated with different concentrations of puerarin (0, 1, 10, 50 uM) before stimulated by ox-LDL (50 ug/mL). Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of puerarin on cell cycle. Proliferating cell nuclear antigen (PCNA) expression and phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2 were detected by western blotting analysis. The results indicated that puerarin significantly inhibited VSMCs proliferation induced by ox-LDL and phosphorylation of ERK 1/2. Furthermore, puerarin also blocked the ox-LDL-induced cell-cycle progression at G1/S-interphase and down-regulated the expression of PCNA of VSMCs. The results suggest puerarin inhibits ox-LDL-induced proliferation of VSMCs by suppressing ERK 1/2 phosphorylation and PCNA expression. PMID- 27004374 TI - SB-431542, a specific inhibitor of the TGF-beta type I receptor inhibits hypoxia induced proliferation of pulmonary artery adventitial fibroblasts. AB - The vascular remodeling process plays an important role in the pathology of hypoxia-induced pulmonary hypertension, and it includes cell proliferation, cell motility, cell synthesis and collagen coagulation. Due to their proliferation and synthesis ability, the adventitial fibroblasts are thought to be critical in the vascular remodeling process initiated in response to hypoxia. However, the factors driving hypoxia-induced fibroblast proliferation and synthesis have yet to be elucidated, and the treatment regimens to treat hypoxia remain ineffective. As forthis study, its purpose was to examine the effects exerted by SB-431542, a small-molecule antagonist of transforming growth factor-beta-receptor, on the proliferation, synthesis and collagen coagulation in cultured adventitial fibroblasts. Another aim of this study was to assess the inhibitory ability of SB 431542 on pulmonary vascular remodeling in chronic hypoxia in vivo.The cell morphology and proliferation of cultured adventitial fibroblasts was assessed by laser confocal microscopy and the MTT assay, respectively. Additionally, collagen synthesis was determined by hydroxyproline chromatography, while the expression of cytokines in adventitial fibroblasts and lung tissues was evaluated by immunohistochemical and reverse transcription PCR analyses. The results indicated that the exposure of cultured fibroblasts to 1% oxygen led to the up regulation of cell proliferation, cell synthesis. In addition, increased expression of cytokines and collagen was detected in vivo in the pulmonary artery adventitia of rats exposed to chronic hypoxia. Conversely, SB-431542 inhibited fibroblast proliferation and synthesis in the process of hypoxia-induced pulmonary hypertension (P < 0.01). Thus, the results suggested that by reducing cell proliferation, cell synthesis of vascular adventitia, small molecule inhibitors of the TGF-beta1 receptors may offer a novel therapy for pulmonary hypertension. PMID- 27004375 TI - Naringin regulates cholesterol homeostasis and inhibits inflammation via modulating NF-kappaB and ERK signaling pathways in vitro. AB - The main purpose of this study was to examine if naringin contributed to the regulation of cholesterol homeostasis and inflammatory cytokine expressions in cholesterol and 25-OH-cholesterol-treated HepG2 cells and TNF-alpha-treated HUVECs. The gene and protein expressions related to cholesterol homeostasis and inflammation were determined by quantitative real-time reverse transcription polymerase chain reaction and Western blotting. We obtained the following results: (1) A concentration-dependent increase of LDLR and CYP7A1 expressions was observed, through activating expressions of SREBP2 and PPARy in HepG2 cells after exposure to naringin; (2) EL gene and protein expressions in HUVECs were inhibited by naringin; (3) the expressions of inflammatory factors such as CRP, TNF-alpha, ICAM-1 and VCAM-1 in HepG2 cells, ICAM-1 and VCAM-1 in HUVECs restrained by naringin were confirmed; (4) NF-kappaB and ERK1/2 activities were quenched by naringin. In summary, naringin might not only effectively reduce cholesterol levels by stimulating cholesterol metabolism but also inhibit inflammatory response through reducing inflammatory cytokine expressions. The effects of naringin were achieved via modulating NF-kappaB and ERK signaling pathways. PMID- 27004377 TI - [New Development in ASA Physical-status Classification]. PMID- 27004376 TI - Antibacterial therapy of aspiration pneumonia in patients with methicillin resistant Staphylococcus aureus-positive sputum: identification of risk factors. AB - Inappropriate antimicrobial treatment could adversely affect the recovery of patients with aspiration pneumonia. We attempted to identify inappropriate antibacterial treatment and to determine the standard use of anti-methicillin resistant Staphylococcus aureus (MRSA) drugs in aspiration pneumonia patients with MRSA-positive in sputum. Aspiration pneumonia patients with MRSA-positive sputum treated between January 2013 and May 2013 were included in this study to determine the risk factors for death during hospitalization. The relationship between anti-MRSA medicine use and death during hospitalization was also investigated. More than 107 MRSA colony-forming units in sputum culture, creatinine clearance of less than 30 mL/min, and quinolone use were found to be risk factors for death during hospitalization. The death rate during hospitalization was significantly lower in cases a Geckler classification of 4 or 5 when anti-MRSA treatment was initiated soon after the culture was obtained. Therefore, we concluded that the use of quinolones as antibacterial treatment in aspiration pneumonia patients with MRSA-positive sputum should be avoided and that anti-MRSA treatment should be started in cases with good quality sputum cultures. PMID- 27004378 TI - [Perioperative Pulmonary Aspiration: Preface and Comments]. AB - Since the risk of pulmonary aspiration was recognized in obstetric anesthesia in 1930's, numerous efforts have been made to reduce the incidence and severity of perioperative pulmonary aspiration: preoperative fasting, preoperative assessment of risk factors in perioperative pulmonary aspiration, emptying the stomach, rapid-sequence induction of anesthesia with cricoid pressure, and the use of a cuffed tracheal tube. With these efforts, the incidence of pulmonary aspiration has been reduced drastically, and aspiration is now rare. Nevertheless, recent large studies have shown that perioperative pulmonary aspiration is the main cause of anesthesia-related death or irreversible brain damage. In this special issue, experts summarize the current state of perioperative pulmonary aspiration, its diagnosis and treatment, risk factors of pulmonary aspiration, preoperative preventative methods, and appropriate anesthesia methods and airway management in patients at increased risk of pulmonary aspiration. PMID- 27004379 TI - [An Overview of Incidence and Outcome of Perioperative Pulmonary Aspiration]. AB - Examination of the literature suggests that the incidence of aspiration pneumonia in the perioperative period is relatively infrequent. Since Mendelson's report of aspiration pneumonitis in 1946, the factors that contribute to the likelihood of aspiration have been identified, and numerous attempts for preventions for regurgitation or pulmonary aspiration have been made. The low incidence of major morbidity of anesthesia-related pulmonary aspiration may be due to adopting quality measures, applying practice guidelines for preoperative fasting, and the use of pharmacologic agents to reduce the risk of pulmonary aspiration. More systematic preoperative checking and more careful selection of patients are necessary when a supraglottic airway is used in preference to a tracheal tube. Second generation supraglottic airways may not reduce the risk of regurgitation, but may reduce the chance of aspiration if the mask position is correct and drain tube works well. Because the mortality and morbidity of aspiration pneumonia remain relatively high, the preoperative risk evaluation is very important to avoid regurgitation or aspiration. PMID- 27004380 TI - [Pathophysiology and Therapeutic Approach of Pulmonary Aspiration]. AB - Pulmonary aspiration is one of the serious adverse events in general anesthesia. Aspiration induced lung injury varies according to the nature of the contents of aspirates (acid or small particles in gastrointestinal tract, bile acid), amount of aspirates, and host-defense status. Early inflammatory responses to acid and small particles from gastrointestinal contents are categorized as aspiration pneumonitis causing rapid respiratory deterioration with early restoration of lung injury within a couple of days. Late phase lung injury is usually "aspiration pneumonia" caused by bacteria colonized in the aspirates. Treatment mainstream is to support respiratory function until the lung resolves from injury. Extracorporeal membrane oxygenation is another promising therapeutic option for cases with severe lung damage to keep the "lung rest" during fulminant lung injury, avoiding further lung damage by injurious ventilation. Empirical administration of antibiotics covering wide spectrum followed by meticulous bacteriological studies to either de-escalate or discontinue antibiotics is crucial. PMID- 27004381 TI - [Patient's Risk Factors for Perioperative Aspiration Pneumonia]. AB - This article reviews patient's own risk factors for perioperative aspiration pneumonia. Maintaining the function of the lower esophageal sphincter (LES), the airway protective reflex, and the oral hygiene are the most important to prevent the pneumonia. The LES is adversely affected by excessive stomach distention, some medication given in perioperative periods, and habitual smoking, as well as pathological status such as esophageal hiatus hernia and achalasia. Postapoplectic patients may have insufficient airway protective reflex including swallowing and laryngeal reflex. It is emphasized that the perioperative oral care is increasing in its importance for the prevention of aspiration pneumonia. PMID- 27004382 TI - [Risk Factors of Perioperative Pulmonary Aspiration Related to Anesthesia, Devices and Operation]. AB - Perioperative pulmonary aspiration is an infrequent but is still a leading cause of anesthesia-related morbidity and mortality. This article reviews risk factors of perioperative pulmonary aspiration related to anesthesia, devices and operation. The most consistent risk factors related to anesthesia are light anesthesia, residual neuromuscular blockade after anesthesia, intermittent positive pressure ventilation particularly with high airway pressure, and prolonged anesthesia. The presence of a supraglottic airway inserted in hypopharynx, multiattempts at tracheal intubation, incorrectly inserted airway, the classic laryngeal mask, airway removal and cuff deflation during recovery of anesthesia, and exchange to a tracheal tube from supraglottic airway increase the risk of aspiration and regurgitation. Even if patients have no predisposing factors, they may become at risk of pulmonary aspiration from a surgical procedure. Patients who are undergoing emergency procedures, bariatric surgery, upper abdominal surgery and laparoscopic surgery should be considered at risk. Lithotomy or the head-down position may also encourage residual gastric contents to regurgitate. PMID- 27004383 TI - [Prevention of Perioperative Aspiration Pneumonitis]. AB - To prevent perioperative aspiration pneumonitis, it is necessary to reduce the volume and acidity of gastric content. The guideline for preoperative fasting published by Japanese Society of Anesthesiologists recommends fasting from intake of clear fluids, breast milk and nonhuman milk at least 2h, 4h and 6h, respectively, before elective procedures requiring general anesthesia, regional anesthesia or sedation/analgesia. Gastrointestinal stimulants, histamine-2 receptor antagonists, proton pump inhibitors, antacids, antiemetics, anticholinergics are effective for reduction of the volume or acidity of gastric content. However, the routine preoperative use of these drugs to reduce the risk of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended. PMID- 27004384 TI - [Prophylaxis of Pulmonary Aspiration during General Anesthesia]. AB - Pulmonary aspiration of gastric or esophageal contents is uncommon; however, it is one of the most severe complications in the perioperative period. The aspiration is associated with possible clinical outcomes, ranging from mild asymptomatic limited episodes of bronchial injury up to the development of a severe acute respiratory distress syndrome. To reduce the incidence of pulmonary aspiration, rapid sequence induction and intubation and awake tracheal intubation are commonly chosen anesthetic techniques for the management of patients at risk of aspiration of gastric or esophageal contents. Although there have been innumerable reports that describe prophylaxis of pulmonary aspiration, currently, there is insufficient evidence to prevent passive regurgitation in at-risk anesthetized patients. Some techniques to prevent pulmonary aspiration entered medical practice on a limited evidence base, but with common sense supporting its use. Properly applied techniques are probably effective at preventing regurgitation in the perioperative period although more randomized controlled trials are awaited to confirm this. Pulmonary aspiration should be prevented using multidisciplinary techniques and considerations that have been shown to improve effectiveness of prophylaxes. However, further research is necessary to support this strategy. PMID- 27004385 TI - [Comparison of the Effect of Periarticular Infiltration Analgesia versus Sciatic Nerve Block for Total Knee Arthroplasty]. AB - BACKGROUND: Sciatic nerve block (SNB) is widely used as a supplemental analgesia after total knee arthroplasty (TKA) combined with femoral nerve block (FNB). Despite its effectiveness, SNB often causes peroneal nerve paralysis, which makes it difficult to detect peroneal nerve injury by surgical process. Recently, periarticular infiltration analgesia (PIA) is reported that it provides analgesia without peroneal nerve paralysis. We conducted a retrospective analysis to compare the effectiveness of SNB and PIA. METHODS: This study was approved by the local institutional ethics committee; 17 patients undergoing TKA under general anesthesia with continuous femoral nerve block were enrolled in the study. All patients received continuous FNB. Nine patients received sciatic nerve block successively, while 8 patients received PIA around the time of insertion of artificial joint. Primary outcome measure was the frequency of peroneal nerve paralysis when the patients woke up. Secondary outcome measures included numerical rating scale (NRS) until postoperative day 3. RESULTS: While there were 6 patients who had peroneal nerve paralysis in the SNB group, none of them had it in the PIA group (P = 0.009). There were no significant differences of the NRSs between the two groups. CONCLUSIONS: PIA provided sufficient analgesia after TKA without peroneal nerve paralysis. PMID- 27004386 TI - [Comparison of Sedative and Analgesic Requirements in Children with and without Down Syndrome following Pediatric Cardiac Surgery]. AB - BACKGROUND: Conflicting results have been reported on postoperative analgesia in pediatric patients with Down syndrome. We compared sedative and analgesic requirements following cardiac surgery between pediatric patients with and without Down syndrome. METHODS: Patients who underwent atrial septal defect closure, ventricular septal defect closure and repair of atrioventricular septal defect at the age between one month and 24 months in our institution for 2 years from 2011 to 2012 were recruited into the study. Patient's background and perioperative managements were investigated. Data collected included preoperative cardiac catheterization data, postoperative sedative and analgesic dosage, postoperative sedation scores and duration of mechanical ventilation. RESULTS: Eight Down syndrome (mean : weight 5.6 kg, age 7.9 months) and twelve non-Down syndrome (mean : weight 5.6 kg, age 5.6 months) patients were enrolled into the study. Pulmonary-systemic artery pressure ratio after cardiac repair and intraoperative anesthetic doses did not differ. Postoperative sedation score, duration of mechanical ventilation and stay in intensive care unit were equivalent. Maintenance and cumulative dose of midazolam, dexmedetomidine and fentanyl, and times of rescue administration did not differ between the groups. CONCLUSIONS: In our study, all enrolled patients received adequate sedation and analgesia after pediatric cardiac surgery. Sedative and analgesic doses following pediatric cardiac surgery were not different between the groups of Down syndrome and non-Down syndrome. PMID- 27004387 TI - [Anesthetic Management of Massive Postpartum Haemorrhage in Which Uterine Compression Sutures Were Used]. AB - BACKGROUND: Uteline compression sutures which preserve portion of placenta tends to cause disseminated intravascular coagulation (DIC). But there have been no reports of anesthetic management of massive postpartum haemorrhage in which uterine compression sutures were used. METHODS: We reviewed the anesthetic management of 9 cases of massive postpartum haemorrhage in which uterine compression sutures were used in our hospital from May 2010 until Sep 2012. RESULTS: Seven cases were complicated by DIC (or the possibility of DIC) and required early infusion of blood products. Six cases required the use of ventilators. All cases recovered and were ultimately discharged. CONCLUSIONS: In the cases of massive postpartum haemorrhage in which uterine compression sutures were used, serious blood loss occurred during the operation, leading to a high probability of the development of DIC. Thus, it is necessary to manage DIC immediately. PMID- 27004388 TI - [The McGRATH MAC Video Laryngoscope Facilitates Probe Insertion during Transesophageal Echocardiography]. AB - BACKGROUND: A transesophageal echocardiography (TEE) probe is often inserted blindly. However, it is desirable to insert it under visual guidance because the blind technique sometimes causes difficulty and may contribute to serious, but rare, complications. This prospective study compared the usefulness of TEE insertion between a brand-new McGRATH MAC video laryngoscope (McGRATH) and a Macintosh laryngoscope (Macintosh). METHODS: We randomly assigned 80 adult patients undergoing cardiovascular surgery into two groups according to the laryngoscope used for TEE probe insertion: the McGRATH (McG Group; n = 40) and Macintosh (MC Group; n = 40) groups. End points included patient demographics, procedure duration, and resistance during insertion (grades 1-5). RESULTS: No differences were found in patient demographics between the groups. There was no significant difference in procedure duration between the groups (P = 0.116). Resistance during insertion was significantly lower in the McG Group than in the MC Group (P < 0.001). There were no failures of insertion in the McG Group. CONCLUSIONS: There were no failures of insertion in the McG Group. Resistance during insertion was lower with the McGRATH than Macintosh. The McGRATH was shown to be very useful when inserting TEE probes. PMID- 27004389 TI - [Anesthesia in a Patient with Giant Goiter in Whom Tracheotomy Was Performed with Standby of Percutaneous Cardiopulmonary Support]. AB - In a 53-year-old female patient total thyroidectomy for a giant goiter under general anesthesia was scheduled. On talking, airway stenosis sounds were heard. Cervical to thoracic CT revealed left and right lobe tumors measuring 5.3 x 5.6 x 10.0 and 9.1 x 8.6 x 10.0 cm, respectively. The trachea showed stenosis at a site 3.8 to 6.5 cm below the glottis, and the narrowest lumen diameter was 3.1 mm. Due to marked tracheal stenosis, awake intubation was not selected. To maintain the airway, tracheotomy was performed under local anesthesia. Considering the risk of difficulty in ventilation during tracheostomy, 4 Fr catheter sheaths were inserted into the right femoral artery and vein for percutaneous cardiopulmonary support (PCPS). Subsequently, tracheotomy was conducted in an area peripheral to the site of stenosis. After tracheotomy, general anesthesia was started. During general anesthesia, there were no problems regarding ventilation. The tracheal cannula was removed 7 days after surgery, and the patient was discharged after 14 days. For general anesthesia in patients with giant goiter, it is important to select an airway management method in consideration of tumor-related compression of the trachea. Airway management by tracheotomy under local anesthesia with standby of PCPS may be a treatment option. PMID- 27004390 TI - [Repeated Anesthesia Management in a Patient with Aicardi Syndrome]. AB - Aicardi syndrome is a rare hereditary disorder that develops in only girls with the trilogy of nutatory epilepsy, callosal agenesis and chorioretinopathy. We experienced general anesthesia twice for a patient with Aicardi syndrome in addition to heavy mental retardation. She underwent surgical correction for cleft lip and palate at 6 months of age and at 2 years of age, respectively. Anesthesia was induced slowly with inhalation of nitrous oxide, oxygen and sevoflurare. After securing an intravenous route, midazolam, thiopental and vecuronium were administered and intubated orally. Anesthesia was maintained with isoflurane safely. Patients with Aicardi syndrome have a high risk of aspiration pneumonia caused by underdeveloped swallowing ability due to callosal agenesis. We should, therefore, pay attention to prevention of seizure and aspiration pneumonia during the perioperative period. PMID- 27004391 TI - [Ischemic Changes in the Electrocardiogram and Circulatory Collapse Accompanied by Severe Anemia Owing to the Delay of Red Blood Cell Concentrate Transfusion in Two Patients with Intraoperative Massive Bleeding]. AB - We present two patients developing intraoperative massive bleeding and showed ischemic changes in the electrocardiogram and circulatory collapse accompanied by severe anemia owing to the delay of red blood cell concentrate transfusion. One patient underwent hepatectomy and the other pancreaticoduodenectomy. Their lowest hemoglobin concentration was around 2 g x dl(-1), and they showed ischemic changes in the electrocardiogram and severe decreases in blood pressure. The former received compatible red blood cell concentrate and the latter received uncrossmatched same blood group red blood cell concentrate immediately, and their electrocardiogram and blood pressure quickly improved. To avoid life-threatening anemia, emergency red blood cell concentrate transfusion including compatible different blood group transfusion should be applied for intraoperative massive bleeding. PMID- 27004392 TI - [A Case of Psychogenic Tremor during Awake Craniotomy]. AB - A 31-year-old woman with a left frontal and parietal brain tumor underwent awake craniotomy. Propofol/remifentanil general anesthesia was induced. Following craniotomy, anesthetic administrations ceased. The level of consciousness was sufficient and she was not agitated. However, the patient complained of nausea 70 minutes into the awake phase. Considering the adverse effects of antiemetics and the upcoming surgical strategy, we did not give any medications. Nausea disappeared spontaneously while the operation was suspended. When surgical intervention extended to the left caudate nucleus, involuntary movement, classified as a tremor, with 5-6 Hz frequency, abruptly occurred on her left forearm. The patient showed emotional distress. Tremor appeared on her right forearm and subsequently spread to her lower extremities. Intravenous midazolam and fentanyl could not reduce her psychological stress. Since the tremor disturbed microscopic observation, general anesthesia was induced. Consequently, the tremor disappeared and did not recur. Based on the anatomical ground and the medication status, her involuntary movement was diagnosed as psychogenic tremor. Various factors can induce involuntary movements. In fact, intraoperative management of nausea and vomiting takes priority during awake craniotomy, but we should be reminded that some antiemetics potentially induce involuntary movement that could be caused by surgery around basal ganglia. PMID- 27004393 TI - [Vasoplegic Syndrome after Aortic Valve Replacement]. AB - We report a case of vasoplegic syndrome (VS) after aortic valve replacement in a 65 year old male with aortic stenosis. The patient developed hypotension after separation from cardiopulmonary bypass (CPB). Transesophageal echocardiography revealed well-maintained cardiac function and normal prosthetic valve function. However, his cardiac index was 3.0 l x min(-1) x m(-2) and systemic vascular resistance index (SVRI) was 1100 dynes x sec(-1) x cm(-5) x m(-2). Diagnosing VS, norepinephrine administration was commenced. Since his respiratory status was good, the patient was extubated on the day of surgery. Two days after surgery, catecholamines were discontinued with the stabilization of his circulatory status. However, his respiratory status showed gradual deterioration, and he was re-intubated. Chest X-ray showed bilateral pleural effusion, which was treated by drainage and fluid restriction. With this, his oxygenation improved and he could be extubated 5 days after surgery. Vasoplegic syndrome is a potentially life threatening complication following cardiac surgery. Hypotension at the time of separation from CPB can be due to multiple factors. Despite an incidence rate of 10%, little is known about VS. We hope that, in future, tailored therapeutic protocols for VS will be developed. PMID- 27004394 TI - [Superior Mesenteric Artery Syndrome following Scoliosis Surgery during Intravenous Patient Controlled Analgesia (IV-PCA) with Fentanyl: A Case Report]. AB - Compression and obstruction of the duodenum can occur after surgical correction of spinal scoliosis. We report a case of 15-year-old girl who developed superior mesenteric artery syndrome (SMAS) following scoliosis surgery. On the 4th postoperative day, the patient complained of nausea and vomiting, which was considered as side effects of opioids as she was treated with intravenous fentanyl infusion with patient-controlled analgesia (PCA) device. Nasogastric tube was placed and background infusion rate of the PCA was tapered. On the 5th postoperative day, fentanyl infusion was stopped, but she complained of persistent nausea and vomiting. Barium upper gastrointestinal series and abdominal echography revealed compression in the third portion of the duodenum between the superior mesenteric artery and aorta on the 7th postoperative day. She responded to conservative treatment (nutritional and fluid supplementation), which lasted about two weeks. She was discharged home on the 51st postoperative day. SMAS is rare but sometimes carries serious complications. Vomiting following scoliosis surgery should be examined thoroughly including the possibility of SMAS, especially during postoperative pain management with opioids (i. e., IV-PCA with fentanyl). Early diagnosis and institution of appropriate conservative therapy is essential to reduce the likelihood of future complications and avoid the need for surgery. PMID- 27004395 TI - [Admiral Isoroku Yamamoto and Chloroform Anesthesia]. AB - Isoroku Yamamoto (1884-1943) who was on the Nisshin, an armored cruiser, received injuries to the left hand and right calf on May 27, 1905, at the Battle of Tsushima during the Russo-Japanese War. Three days later, he was admitted to the Sasebo Naval Hospital to undergo emergency amputations of the index and middle fingers of the left hand under chloroform anesthesia. He was, then, evacuated to the Yokosuka Naval Hospital, one of the naval background hospitals, and approximately, a month later, he received a muscle grafting taken from the left gluteal region. The procedure was most likely performed under chloroform anesthesia because chloroform was the only general anesthetic that the hospitals prepared. This grafting was not described in most of his biographies. In December 1916, he suffered from acute appendicitis and he was brought to the University of Tokyo Hospital, where an appendectomy was undertaken by Professor Tsugushige Kondo using chloroform ansthesia because Kondo had a great dislike for spinal anesthesia. PMID- 27004396 TI - [Optimization of cluster analysis based on drug resistance profiles of MRSA isolates]. AB - We examined 402 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from clinical specimens in our hospital between November 19, 2010 and December 27, 2011 to evaluate the similarity between cluster analysis of drug susceptibility tests and pulsed-field gel electrophoresis (PFGE). The results showed that the 402 strains tested were classified into 27 PFGE patterns (151 subtypes of patterns). Cluster analyses of drug susceptibility tests with the cut off distance yielding a similar classification capability showed favorable results--when the MIC method was used, and minimum inhibitory concentration (MIC) values were used directly in the method, the level of agreement with PFGE was 74.2% when 15 drugs were tested. The Unweighted Pair Group Method with Arithmetic mean (UPGMA) method was effective when the cut-off distance was 16. Using the SIR method in which susceptible (S), intermediate (I), and resistant (R) were coded as 0, 2, and 3, respectively, according to the Clinical and Laboratory Standards Institute (CLSI) criteria, the level of agreement with PFGE was 75.9% when the number of drugs tested was 17, the method used for clustering was the UPGMA, and the cut-off distance was 3.6. In addition, to assess the reproducibility of the results, 10 strains were randomly sampled from the overall test and subjected to cluster analysis. This was repeated 100 times under the same conditions. The results indicated good reproducibility of the results, with the level of agreement with PFGE showing a mean of 82.0%, standard deviation of 12.1%, and mode of 90.0% for the MIC method and a mean of 80.0%, standard deviation of 13.4%, and mode of 90.0% for the SIR method. In summary, cluster analysis for drug susceptibility tests is useful for the epidemiological analysis of MRSA. PMID- 27004397 TI - [Comparison of the clinical effectiveness of three neuraminidase inhibitors for Japanese pediatric patients with influenza in the 2013/2014 season]. AB - We investigated the clinical symptoms of 206 pediatric patients with influenza virus infection and compared them among oseltamivir-treated, zanamivir-treated, and laninamivir-treated groups in 2013/2014 influenza season. The drug compliance of each neuraminidase inhibitor was good in all three groups. Although the duration of fever after administration of the first dose of each neuraminidase inhibitor were significantly prolonged in the patient with influenza B infection than in the patient with influenza A infection, no statistically significant difference in the clinical efficacy and the side effect among three groups were found. The number of biphasic fever episodes in patients treated with neuraminidase inhibitor was rare (two episodes of oseltamivir-treated group and one episode of zanamivir-treated group). In conclusion, under the good drug compliance, the efficacy of all three neuraminidase inhibitor was the same for the treatment of influenza virus infection in children. PMID- 27004398 TI - [Recent epidemiology of Clostridium difficile infection in Japan]. AB - Clostridium difficile (C. difficile) is a major pathogen for diarrhea in hospitalized patients and because of outbreak of highly virulent strain in EU and US, increased length of hospital stay and increased numbers of severe patients and deaths have become major challenges. In recent years, transmissions through community-acquired or food-borne infections are reported. National surveillance has been already performed overseas. Guidelines for preventing C. difficile infection (CDI) is available, and education activities are promoted for preventing the infection spread. Meanwhile, in Japan, medical hospitals are reporting individual CDI incidence, however, a large-scale research has not been conducted up to the present date and therefore the entire status of CDI including infection of the highly virulent strain has yet to be revealed. This time, we performed a questionnaire-based survey at 2,537 hospitals nationwide between April 15, 2013 and May 31, 2013 to investigate CDI incidence, diagnosis and treatment. Valid responses were obtained from 321 hospitals. Regarding the annual number of CDI patients at all the hospitals, the highest group of hospitals responding "1 to 5 patients a year" was 17.8%, and the second highest group of hospitals responding "no patients a year" was 13.1%. In contrast, there was a group of hospitals with "more than 101 patients a year", which was 3.1%. This indicates that there was the difference in the CDI incidences among hospitals. According to the questionnaire results, a highest group of hospitals responding "0-20%" for CDI patients with serious complication such as toxic megacolon, gastrointestinal perforation, ileus paralytic, bacteremia, sepsis, crohn's disease, and ulcerative colitis was 62.6%, and for CDI patients with recurrence more than one, a group of hospitals answering "0 to 20%" was 56.4%, which was the highest. This suggested that there was only a small number of serious CDI patients and recurrence CDI patients in Japan. For rapid toxin detection kit used in CDI diagnosis, a group of hospitals using "C. DIFF QUIK CHEK COMPLETE" was over 40%, which showed that the kit was a major product used in Japan. And a group of institutions responding that they will start antibacterial medication such as vancomycin (VCM) and metronidazole (MNZ) as soon as after rapid diagnostic test, etc. showing positive results was over 70%. As for CDI treatment, a highest group of hospitals answering that VCM is administered orally at a dose of "0.5 g four times daily" was 42.1%, and a group of hospitals responding "10 to 14 days" for administration period was 44.2%, which was the highest. A highest group of hospitals answering that MNZ is administered orally at a dose of "250 mg four times daily" was 38.3%, and a group of hospitals responding "10 to 14 days" for administration period was 46.4%, which was the highest. Apart from VCM and MNZ, probiotics are also used for CDI treatment, "butyric acid bacterium" accounted for 40.8% in the probiotics group, which was the highest, followed by "bifidobacteria" 37.7% and "resistant lactic acid bacterium" 25.6%. To prevent the spread of CDI, 47.7% of the hospitals responded that the patients are "isolated", while 25.6% answered the patients are "sometimes isolated", which means that more than 70% of patients are "isolated or sometimes isolated". As to what type of antiseptic drug is used for sterilizing hospital, 68.2% of the hospitals answered that they are using "sodium hypochlorite 1,000 ppm". The survey more than 300 hospitals have revealed not only the CDI incidences, timing of toxin test, and part of the actual therapeutic strategy at medical institutions in Japan but also the difference in the CDI incidences and therapeutic strategy among hospitals. In the future, epidemiological data on epidemic strain will be accumulated more in Japan as are done overseas, and guidelines for CDI diagnosis and treatment will need to be formulated. PMID- 27004399 TI - Uncommon nucleotide excision repair phenotypes revealed by targeted high throughput sequencing. AB - BACKGROUND: Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS). METHODS: Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies). RESULTS: We identified causative mutations in 17 out of the 40 patients (43%). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV sensitive syndrome and in two cases with mixed XP/CS phenotypes. CONCLUSIONS: Our study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects. PMID- 27004400 TI - MAPK1E322K mutation increases head and neck squamous cell carcinoma sensitivity to erlotinib through enhanced secretion of amphiregulin. AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have not been effective in unselected head and neck squamous cell carcinoma (HNSCC) populations. We previously reported an exceptional response to a brief course of erlotinib in a patient with advanced HNSCC whose tumor harbored a MAPK1E322K somatic mutation. MAPK1E322Kwas associated with increased p-EGFR, increased EGFR downstream signaling and increased sensitivity to erlotinib. In this study, we investigated the mechanism of MAPK1E322K-mediated EGFR activation in the context of erlotinib sensitivity. We demonstrated increased AREG secretion in HNSCC cell lines harboring endogenous or exogenous MAPK1E322K compared to wild type MAPK1. We found inhibition or knockdown of MAPK1 with siRNA resulted in reduced secretion of AREG and decreased sensitivity to erlotinib in the setting of MAPK1E322K. MAPK1E322K was associated with increased AREG secretion leading to an autocrine feedback loop involving AREG, EGFR and downstream signaling. Knockdown of AREG in HNSCC cells harboring MAPK1E322K abrogated EGFR signaling and decreased sensitivity to erlotinib in vitro and in vivo. These cumulative findings implicate increased AREG secretion and EGFR activation as contributing to increased erlotinib sensitivity in MAPK1E322K HNSCC. PMID- 27004401 TI - Protein phosphatase, Mg2+/Mn2+-dependent 1A controls the innate antiviral and antibacterial response of macrophages during HIV-1 and Mycobacterium tuberculosis infection. AB - Co-infection with HIV-1 and Mycobacterium tuberculosis (Mtb) is a major public health issue. While some research has described how each pathogen accelerates the course of infection of the other pathogen by compromising the immune system, very little is known about the molecular biology of HIV-1/Mtb co-infection at the host cell level. This is somewhat surprising, as both pathogens are known to replicate and persist in macrophages. We here identify Protein Phosphatase, Mg2+/Mn2+ dependent 1A (PPM1A) as a molecular link between Mtb infection and increased HIV 1 susceptibility of macrophages. We demonstrate that both Mtb and HIV-1 infection induce the expression of PPM1A in primary human monocyte/macrophages and THP-1 cells. Genetic manipulation studies revealed that increased PPMA1 expression rendered THP-1 cells highly susceptible to HIV-1 infection, while depletion of PPM1A rendered them relatively resistant to HIV-1 infection. At the same time, increased PPM1A expression abrogated the ability of THP-1 cells to respond to relevant bacterial stimuli with a proper cytokine/chemokine secretion response, blocked their chemotactic response and impaired their ability to phagocytose bacteria. These data suggest that PPM1A, which had previously been shown to play a role in the antiviral response to Herpes Simplex virus infection, also governs the antibacterial response of macrophages to bacteria, or at least to Mtb infection. PPM1A thus seems to play a central role in the innate immune response of macrophages, implying that host directed therapies targeting PPM1A could be highly beneficial, in particular for HIV/Mtb co-infected patients. PMID- 27004402 TI - Oncogenic AKT1(E17K) mutation induces mammary hyperplasia but prevents HER2 driven tumorigenesis. AB - One of the most frequently deregulated signaling pathways in breast cancer is the PI 3-K/Akt cascade. Genetic lesions are commonly found in PIK3CA, PTEN, and AKT, which lead to excessive and constitutive activation of Akt and downstream signaling that results in uncontrolled proliferation and increased cellular survival. One such genetic lesion is the somatic AKT1(E17K) mutation, which has been identified in 4-8% of breast cancer patients. To determine how this mutation contributes to mammary tumorigenesis, we constructed a genetically engineered mouse model that conditionally expresses human AKT1(E17K) in the mammary epithelium. Although AKT1(E17K) is only weakly constitutively active and does not promote proliferation in vitro, it is capable of escaping negative feedback inhibition to exhibit sustained signaling dynamics in vitro. Consistently, both virgin and multiparous AKT1(E17K) mice develop mammary gland hyperplasia that do not progress to carcinoma. This hyperplasia is accompanied by increased estrogen receptor expression, although exposure of the mice to estrogen does not promote tumor development. Moreover, AKT1(E17K) prevents HER2-driven mammary tumor formation, in part through negative feedback inhibition of RTK signaling. Analysis of TCGA breast cancer data revealed that the mRNA expression, total protein levels, and phosphorylation of various RTKs are decreased in human tumors harboring AKT1(E17K). PMID- 27004403 TI - Integrated analysis of long non-coding RNAs in human colorectal cancer. AB - Accumulating evidence highlights the role of long non-coding RNAs (lncRNAs) in tumors. However, the genome-wide expression and roles of lncRNAs in colorectal cancer (CRC) remain unknown. Here, we systematically examined the global gene expressions in primary and synchronous liver metastases CRC tissue, in which thousands of aberrantly expressed lncRNAs were characterized. Co-expression analysis revealed that some lncRNAs correlated to their neighboring mRNAs in expression levels, whereas others formed networks with protein-coding genes in trans. We observed H3K4me3 was enriched at expressed lncRNA transcription start sites (TSSs) and correlated to dysregulated lncRNAs. Furthermore, we identified primary and metastasis tumor linked lncRNA signatures positively correlated with poor-prognosis gene set. Finally, functional experiments demonstrated two candidate lncRNAs were required for proliferation and migration of CRC cells. In summary, we provided a new framework for lncRNA associated clinical prognosis evaluation and target selection of gene therapy in CRC. PMID- 27004404 TI - Repurposing metformin for cancer treatment: current clinical studies. AB - In recent years, several studies have presented evidence suggesting a potential role for metformin in anti-cancer therapy. Preclinical studies have demonstrated several anticancer molecular mechanisms of metformin including mTOR inhibition, cytotoxic effects, and immunomodulation. Epidemiologic data have demonstrated decreased cancer incidence and mortality in patients taking metformin. Several clinical trials, focused on evaluation of metformin as an anti-cancer agent are presently underway. Data published from a small number of completed trials has put forth intriguing results. Clinical trials in pre-surgical endometrial cancer patients exhibited a significant decrease in Ki67 with metformin monotherapy. Another interesting observation was made in patients with breast cancer, wherein a trend towards improvement in cancer proliferation markers was noted in patients without insulin resistance. Data on survival outcomes with the use of metformin as an anti-cancer agent is awaited. This manuscript will critically review the role of metformin as a potential cancer treatment. PMID- 27004405 TI - Genomic landscape of DNA repair genes in cancer. AB - DNA repair genes are frequently mutated in cancer, yet limited data exist regarding the overall genomic landscape and functional implications of these alterations in their entirety. We created comprehensive lists of DNA repair genes and indirect caretakers. Mutation, copy number variation (CNV), and expression frequencies of these genes were analyzed in COSMIC. Mutation co-occurrence, clinical outcomes, and mutation burden were analyzed in TCGA. We report the 20 genes most frequently with mutations (n > 19,689 tumor samples for each gene), CNVs (n > 1,556), or up- or down-regulated (n = 7,998). Mutual exclusivity was observed as no genes displayed both high CNV gain and loss or high up- and down regulation, and CNV gain and loss positively correlated with up- and down regulation, respectively. Co-occurrence of mutations differed between cancers, and mutations in many DNA repair genes were associated with higher total mutation burden. Mutation and CNV frequencies offer insights into which genes may play tumor suppressive or oncogenic roles, such as NEIL2 and RRM2B, respectively. Mutual exclusivities within CNV and expression frequencies, and correlations between CNV and expression, support the functionality of these genomic alterations. This study provides comprehensive lists of candidate genes as potential biomarkers for genomic instability, novel therapeutic targets, or predictors of immunotherapy efficacy. PMID- 27004406 TI - Cell line with endogenous EGFRvIII expression is a suitable model for research and drug development purposes. AB - Glioblastoma is the most common and malignant brain tumor, characterized by high cellular heterogeneity. About 50% of glioblastomas are positive for EGFR amplification, half of which express accompanying EGFR mutation, encoding truncated and constitutively active receptor termed EGFRvIII. Currently, no cell models suitable for development of EGFRvIII-targeting drugs exist, while the available ones lack the intratumoral heterogeneity or extrachromosomal nature of EGFRvIII.The reports regarding the biology of EGFRvIII expressed in the stable cell lines are often contradictory in observations and conclusions. In the present study, we use DK-MG cell line carrying endogenous non-modified EGFRvIII amplicons and derive a sub-line that is near depleted of amplicons, whilst remaining identical on the chromosomal level. By direct comparison of the two lines, we demonstrate positive effects of EGFRvIII on cell invasiveness and populational growth as a result of elevated cell survival but not proliferation rate. Investigation of the PI3K/Akt indicated no differences between the lines, whilst NFkappaB pathway was over-active in the line strongly expressing EGFRvIII, finding further supported by the effects of NFkappaB pathway specific inhibitors. Taken together, these results confirm the important role of EGFRvIII in intrinsic and extrinsic regulation of tumor behavior. Moreover, the proposed models are stable, making them suitable for research purposes as well as drug development process utilizing high throughput approach. PMID- 27004407 TI - Triptolide has anticancer and chemosensitization effects by down-regulating Akt activation through the MDM2/REST pathway in human breast cancer. AB - Triptolide has been shown to exhibit anticancer activity. However, its mechanism of action is not clearly defined. Herein we report a novel signaling pathway, MDM2/Akt, is involved in the anticancer mechanism of triptolide. We observed that triptolide inhibits MDM2 expression in human breast cancer cells with either wild type or mutant p53. This MDM2 inhibition resulted in decreased Akt activation. More specifically, triptolide interfered with the interaction between MDM2 and the transcription factor REST to increase expression of the regulatory subunit of PI3-kinase p85 and consequently inhibit Akt activation. We further showed that, regardless of p53 status, triptolide inhibited proliferation, induced apoptosis, and caused G1 phase cell cycle arrest. Triptolide also enhanced the cytotoxic effect of doxorubicin. MDM2 inhibition plays a causative role in these effects. The inhibitory effect of triptolide on MDM2-mediated Akt activation was eliminated with MDM2 overexpression. MDM2-overexpressing tumor cells, in turn, were less susceptible to the anticancer and chemosensitization effects of triptolide than control cells. Triptolide also exhibited anticancer and chemosensitization effects in nude mouse xenograft model. When it was administered to tumor-bearing nude mice, triptolide inhibited tumor growth and enhanced the antitumor effects of doxorubicin. In summary, triptolide has anticancer and chemosensitization effects by down-regulating Akt activation through the MDM2/REST pathway in human breast cancer. Our study helps to elucidate the p53-independent regulatory function of MDM2 in Akt signaling, offering a novel view of the mechanism by which triptolide functions as an anticancer agent. PMID- 27004409 TI - Erratum to: Osteogenic differentiation of dental pulp stem cells under the influence of three different materials. PMID- 27004410 TI - Association between hypertension and deep vein thrombosis after orthopedic surgery: a meta-analysis. AB - BACKGROUND: We aimed to analyze the association between hypertension and deep vein thrombosis (DVT) after orthopedic surgery. METHODS: Relevant studies were identified by a search of PubMed, Embase, China National Knowledge Infrastructure, Wanfang, the Chinese Biomedical Literature, and Weipu database until December 2015. The association between hypertension and DVT after orthopedic surgery was assessed by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was evaluated by the Chi-square test based on Q statistic and I(2) statistics. Finally, publication bias was evaluated by Egger's test. RESULTS: A total of 16 articles with 68,955 males and 53,057 females were eventually identified. Studies yielded effects for homogeneous (Q = 38.41, P = 0.0008, and I(2) = 60.9%). Meta-analysis showed that hypertension was associated with DVT orthopedic surgery (OR 2.89, 95% CI 2.18-3.83, Z = 7.38, P < 0.05). No statistical evidence of publication bias was found among studies (t = 1.90, P = 0.08). The funnel plot was symmetry, and the results were reliable. CONCLUSIONS: Hypertension may promote DVT after orthopedic surgery, and may be an important risk factor of DVT occurrence. PMID- 27004411 TI - Isoflavone supplementation in postmenopausal women does not affect leukocyte LDL receptor and scavenger receptor CD36 expression: A double-blind, randomized, placebo-controlled trial. AB - SCOPE: Isoflavones are discussed to improve serum lipoproteins and body composition and to reduce cardiovascular disease risk in postmenopausal women (PMW). LDL receptors (LDLR) and scavenger receptor CD36 (CD36) play a pivotal role in the regulation of plasma LDL-cholesterol concentrations (LDL-chol). We investigated the impact of isoflavones on the receptor expression of both receptors in leukocytes of PMW. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial in parallel design was conducted to assess the effects of an isoflavone-enriched soy extract (117.4 mg/day isoflavone aglycone equivalents) for 12 weeks on serum LDL-chol, LDLR, and CD36 expression on leukocytes in 170 healthy PMW. Baseline and after 12 weeks, blood lipid concentrations, anthropometric data and body composition were determined. Receptor expression on leukocytes was measured by means of flow cytometry. After the intervention, no significant differences were found for LDLR and CD36 expression on leukocytes. A significant increase of serum LDL-chol was shown for the isoflavone group (p = 0.03) after 12 weeks. Body fat content and VAT were not affected. CONCLUSION: Isoflavone supplementation for 12 weeks did not change LDLR and CD36 expression on leukocytes of PMW and did not affect body fat content and visceral adipose tissue (VAT), but slightly increased serum LDL-chol. PMID- 27004408 TI - Plasminogen activator inhibitor-1 enhances radioresistance and aggressiveness of non-small cell lung cancer cells. AB - Acquired resistance of tumor cells during treatment limits the clinical efficacy of radiotherapy. Recent studies to investigate acquired resistance under treatment have focused on intercellular communication because it promotes survival and aggressiveness of tumor cells, causing therapy failure and tumor relapse. Accordingly, a better understanding of the functional communication between subpopulations of cells within a tumor is essential to development of effective cancer treatment strategies. Here, we found that conditioned media (CM) from radioresistant non-small cell lung cancer (NSCLC) cells increased survival of radiosensitive cells. Comparative proteomics analysis revealed plasminogen activator inhibitor-1 (PAI-1) as a key molecule in the secretome that acts as an extracellular signaling trigger to strengthen resistance to radiation. Our results revealed that expression and secretion of PAI-1 in radioresistant cells was increased by radiation-induced transcription factors, including p53, HIF 1alpha, and Smad3. When CM from radioresistant cells was applied to radiosensitive cells, extracellular PAI-1 activated the AKT and ERK1/2 signaling pathway and inhibited caspase-3 activity. Our study also proposed that PAI-1 activates the signaling pathway in radiosensitive cells via extracellular interaction with its binding partners, not clathrin-mediated endocytosis. Furthermore, secreted PAI-1 increased cell migration capacity and expression of EMT markers in vitro and in vivo. Taken together, our findings demonstrate that PAI-1 secreted from radioresistant NSCLC cells reduced radiosensitivity of nearby cells in a paracrine manner, indicating that functional inhibition of PAI-1 signaling has therapeutic potential because it prevents sensitive cells from acquiring radioresistance. PMID- 27004412 TI - Perioperative hemodynamic optimization using the photoplethysmography in colorectal surgery (the PANEX3 trial): study protocol for a randomized controlled trial. AB - BACKGROUND: Photoplethysmography with a digital sensor (ClearSight, Edwards Lifesciences, Irvine, CA, USA) connected to a dedicated monitor (EV 1000, Edwards Lifesciences) was recently proposed for use in performing hemodynamic optimization during surgery. The objective of this study is to evaluate the effect of photoplethysmography on the incidence of postoperative complications compared with the conventional hemodynamic algorithm, which uses mean arterial pressure. METHODS/DESIGN: The hemodynamic optimization using photoplethysmography (PANEX3) trial is a monocentric, randomized, single-blind, controlled, two parallel arm, superiority trial, randomizing 160 patients with an intermediate risk of postoperative complications after colorectal surgery. Informed consent will be obtained from all participants. The hemodynamic optimization is conducted using a specified hemodynamic algorithm either with photoplethysmography (the photoplethysmography group) or with conventional mean arterial pressure (the control group). The anesthesiologist performed a 1:1 randomization the day before surgery using a scratch card, which is available 24/7. The randomization sequence is generated using permutated blocks. Both the patients and surgeons are blinded to the allocation group. The primary outcome is the incidence of at least one postoperative complication during the 30 days following surgery. Two independent experts, who were blinded to the group allocations, validate the complication for each patient using an a priori classification. The secondary outcomes are to study the total number of postoperative complications, the real length of hospital stays, and the postoperative mortality between each group. DISCUSSION: The PANEX3 trial is the first randomized controlled study conducted to investigate whether perioperative hemodynamic optimization using photoplethysmography during colorectal surgery could decrease the incidence of patients having at least one postoperative complication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02343601. PMID- 27004413 TI - The timing of tuberculosis after isoniazid preventive therapy among gold miners in South Africa: a prospective cohort study. AB - BACKGROUND: The durability of isoniazid preventive therapy (IPT) in preventing tuberculosis (TB) is limited in high-prevalence settings. The underlying mechanism (reactivation of persistent latent TB or reinfection) is not known. We aimed to investigate the timing of TB incidence during and after IPT and associated risk factors in a very high TB and HIV-prevalence setting, and to compare the observed rate with a modelled estimate of TB incidence rate after IPT due to reinfection. METHODS: In a post-hoc analysis of a cluster-randomized trial of community-wide IPT among South African gold miners, all intervention arm participants that were dispensed IPT for at least one of the intended 9 months were included. An incident TB case was defined as any participant with a positive sputum smear or culture, or with a clinical TB diagnosis assigned by a senior study clinician. Crude TB incidence rates were calculated during and after IPT, overall and by follow-up time. HIV status was not available. Multivariable Cox regression was used to analyse risk factors by follow-up time after IPT. Estimates from a published mathematical model of trial data were used to calculate the average reinfection TB incidence in the first year after IPT. RESULTS: Among 18,520 participants (96% male, mean age 41 years, median follow-up 2.1 years), 708 developed TB. The TB incidence rate during the intended IPT period was 1.3/100 person-years (pyrs; 95% confidence interval (CI), 1.0-1.6) and afterwards 2.3/100 pyrs (95% CI, 1.9-2.7). TB incidence increased within 6 months followed by a stable rate over time. There was no evidence for changing risk factors for TB disease over time after miners stopped IPT. The average TB incidence rate attributable to reinfection in the first year was estimated at 1.3/100 pyrs, compared to an observed rate of 2.2/100 pyrs (95% CI, 1.8-2.7). CONCLUSIONS: The durability of protection by IPT was lost within 6-12 months in this setting with a high HIV prevalence and a high annual risk of M. tuberculosis infection. The observed rate was higher than the modelled rate, suggesting that reactivation of persistent latent infection played a role in the rapid return to baseline TB incidence. PMID- 27004414 TI - Polymorphisms in FADS1 and FADS2 alter plasma fatty acids and desaturase levels in type 2 diabetic patients with coronary artery disease. AB - BACKGROUND: To explore whether plasma fatty acids and SNPs in the fatty acid desaturase (FADS) gene associated with type 2 diabetes (T2D) and coronary artery disease (CAD). METHODS: In this cross-sectional study, we utilized gas chromatography-mass spectrometric analysis and the high-resolution melting method to detect plasma fatty acids and SNPs respectively (rs174537G>T, rs174616C>T, rs174460T>C, and rs174450A>C) in 234 T2D, 200 CAD, 185 T2D&CAD patients, and 253 healthy controls. RESULTS: We found that T2D&CAD patients had the highest plasma arachidonic acid, dihomo-gamma-linolenic acid and delta-6 desaturase, and the lowest stearic acid, linolenic acid, and saturated fatty acids; plasma eicosapentaenoic acid and docosahexaenoic acid elevated in T2D patients, but significantly reduced in CAD patients. Moreover, T2D patients with rs174537 GG genotype were at risk of developing T2D&CAD (odds ratio (OR) 1.763; 95 % CI 1.143 2.718; p = 0.010), with elevated plasma LDL-cholesterol, arachidonic acid, and delta-6 desaturase. CONCLUSIONS: Our results show that SNPs in FADS gene (particularly rs174537) associate with plasma fatty acids and desaturase levels in patients with both T2D and CAD, which maybe increases the risk of CAD in diabetic patients. PMID- 27004415 TI - Effect of Surface Chemistry on the Mechanisms and Governing Laws of Friction and Wear. AB - Recent studies have shown that interface chemistry, that is, the formation and breaking of chemical bonds across contacting interfaces, is closely related to the wear and friction behavior at the nanoscale. In reality, the dangling bond density (DBD) at contacting surfaces can vary greatly. Currently, it remains unclear how friction and wear mechanisms depend on DBDs and whether the Archard's law for wear and Amonton's law for friction are still applicable for contacting surfaces with different DBDs. In this work, we address these issues by studying the wear and friction behavior between two sliding diamond-like carbon surfaces by controlling DBDs via hydrogenation using molecular dynamics simulations. It is found that the chemical bond breaking and remaking across the contacting interface play the key role in determining the friction and wear behavior. During the sliding, a higher DBD leads to more chemical bond formations across the interface, causing stronger wear via either atom or cluster detachments. With the same DBD, a mechanism transition from an atom-by-atom to cluster detachments is observed by increasing the normal load. Remarkably, a fully saturated surface can exhibit a wearless friction. We further show that after necessary modifications, the Archard's law for wear and the Amonton's law for friction may be applicable at the nanoscale. The present work reveals insights into the effect of interface chemistry on the friction and wear, and it provides guidelines for effective antiwear design. PMID- 27004416 TI - Current and future perspectives on the systematics, taxonomy and nomenclature of testate amoebae. AB - Testate amoebae are a polyphyletic assemblage of at least three major, unrelated taxonomic groups of unicellular amoeboid eukaryotes exhibiting a test. The focus on testate amoebae in scientific research has greatly increased in the past 20 years: from an average of about 5 papers a year in the mid-1990s to the current rate of more than 50 papers published yearly. The application range of these organisms is rapidly expanding as well: from the traditional fields of environmental monitoring and paleoecology, to forensic sciences and ecotoxicology studies. These developments are nevertheless strongly dependent on reliable taxonomy and nomenclature. However, scientometric data reveal that despite an ever-increasing necessity for the use of names (the product of taxonomy), the corresponding effort has not been achieved for improving testate amoebae systematics. As a consequence, inaccurate taxonomy yields to misinterpretations in the diversity of the organisms and to potentially incorrect conclusions. These and related problems are discussed in this study, highlighting the outcome of poor taxonomic expertise in accurate classification and phylogeny of testate amoebae, and the consequences derived from it. Additionally, this study is aimed to discuss the current status of testate amoebae classification, and to present all nomenclature and taxonomic changes in higher and lower taxonomic levels of testate amoebae, as a result of recent molecular reconstructions. Finally, we conclude with a list of the needs and suggestions toward a unified and modernized taxonomy of testate amoebae. PMID- 27004417 TI - Protist metabarcoding and environmental biomonitoring: Time for change. AB - High-throughput amplicon sequencing of environmental DNA and/or RNA proved to be a powerful tool to describe protist diversity. This new approach called also the metabarcoding has totally transformed our view of protist diversity, revealing a large number of novel lineages and expanding the range of protist phylogenetic diversity at almost every taxonomic level. However, until now the objectives of the vast majority of metabarcoding studies were purely academic. Practical applications of protist metabarcoding are surprisingly scarce, despite the fact that several groups of protists are commonly used as bioindicators of environmental impacts in freshwater or marine ecosystems. Here, we are reviewing studies that examine the ecological applications of metabarcoding for two groups of well-known protist bioindicators: diatoms and foraminifera. The results of these studies show that despite some biological and technical biases, molecular data quite faithfully reflect the morphology-based biotic indices and provide a similar assessment of ecosystem status. In view of these results, protist metabarcoding appears as a rapid and accurate tool for the evaluation of the quality of aquatic ecosystems. Hence, we plead for integration of protist metabarcoding in future biomonitoring projects as a complement of traditional methods and a source of new biosensors for environmental impact assessment. PMID- 27004419 TI - Differentiated therapy in pre- and postmenopausal adnexal torsion based on malignancy rates: A retrospective multicentre study over five years. AB - INTRODUCTION: The purpose of this study was to investigate the clinical presentation, intra and postoperative outcomes in pre and postmenopausal women who underwent operations for adnexal torsion, and to define our experience diagnosing and managing postmenopausal women with adnexal torsion. METHODS: One hundred and fifty-seven patients who underwent operation with a diagnosis of adnexal torsion were analyzed according to demographic characteristics, menopausal status, preoperative signs and symptoms, surgical findings and applied surgical procedures, and pathological results in four tertiary centers. RESULTS: The main indication for surgery for the postmenopausal women was pelvic mass (58% vs. 40%), while for premenopausal women the main indication was suspicion of torsion (55% vs. 24%), (each p < 0.001). The duration of time between being admitted to the hospital and entering operating room as well as the duration of surgery and postoperative hospitalization were statistically longer in the postmenopausal group (each p < 0.001). While extensive surgeries were performed for 68% of the postmenopausal group, this was required for only 3% of the premenopausal group. Functional cysts were the most common pathologic finding in premenopausal women, and only 2 cases of malignancy (1.6%) were seen as opposed to the postmenopausal group, where malignancy was diagnosed in 16% of cases (p < 0.001). DISCUSSION: Adnexal torsion in postmenopausal women is an uncommon event. Malignancy risk should be considered before operation. CONCLUSION: The malignancy rate was 16% in postmenopausal women with adnexal torsion. Thus, extensive surgeries are more common in postmenopausal women with adnexal torsion. PMID- 27004418 TI - Superiority of resection over enucleation for schwannomas of the cervical vagus nerve: A retrospective cohort study of 22 consecutive patients. AB - INTRODUCTION: Schwannoma of the cervical vagus nerve is rare. Treatment options include intracapsular enucleation and en bloc resection. The purpose of this study was to compare the outcomes of enucleation and resection in terms of postoperative mortality and morbidity, freedom from vocal cord palsy, freedom from local recurrence, quality-adjusted life-year (QALY) and vocal handicap index (VHI). METHODS: Twentytwo consecutive patients were divided into two groups. Patients in group A (n = 9) underwent intracapsular enucleation, whereas patients in Group B (n = 13) underwent en bloc resection. Main endpoints of the study were postoperative mortality and morbidity, freedom from vocal cord palsy, freedom from local recurrence and quality of life. The quality of life after surgery was assessed according to the quality-adjusted life-year (QALY) EQ-5D-5L methodology, and calculation of the voice handicap index (VHI). RESULTS: Postoperative mortality was nil. Morbidity included 1 wound dehiscence in group A and 2 transitory dysphagias in group B. Freedom from vocal cord palsy was 22% in group A and zero in group B (p = 0.15). Operation-specific local recurrence rate was 33% (3/9 patients) in group A and nil in group B (0/23 patients) (p = 0.05). QALYs was 0.55 in group A and 0.54 in group B (p = 1.0). VHI was 23.77 in group A and 26.15 in group B (p = 1.00). CONCLUSION: Resection is superior to enucleation in terms of freedom from local recurrence. Functional results are comparable for both techniques. PMID- 27004420 TI - Introduction to small renal tumours and prognostic indicators. AB - Over the past years, the widespread use of radiological imaging for evaluating abdominal symptoms unrelated to kidney cancer has been linked to a significant increase in the percentage of renal tumours incidentally detected at an asymptomatic stage. The definition of 'small' renal tumours has changed over the years. Presently, according to dimensional criteria, surgical indications and prognostic impact, small renal tumours are defined as masses <=4 cm in size. Classical preoperative variables that influence the decision-making process in the management of T1a renal tumours can be classified as patient-related and tumour-related factors. Age is an independent predictor of cancer-specific survival (CSS), with older patients exhibiting significantly worse survival. An accurate classification of the anatomical and topographical characteristics of small renal masses based on available nephrometry systems is necessary for standard preoperative evaluation of patients eligible for partial nephrectomy (PN). Renal tumour biopsies (RTBs) can be indicated in patients eligible for active surveillance or ablative treatments, those with other primary tumours, those with prior renal lesions and/or those with multiple synchronous tumours, showing a median diagnostic rate of 92%. Small renal tumours typically have a good prognosis. Patient age, mode of presentation, nuclear grading, coagulative necrosis and histologic subtype can influence the prognosis of this subgroup of RCC. PMID- 27004422 TI - Reply to the letter on "Effect of fruits and vegetables on metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials". PMID- 27004421 TI - Higher maternal leptin levels at second trimester are associated with subsequent greater gestational weight gain in late pregnancy. AB - BACKGROUND: Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. In non-pregnant populations, low leptin levels stimulate positive energy balance. In pregnancy, both the placenta and adipose tissue contribute to circulating leptin levels. We tested whether maternal leptin levels are associated with subsequent GWG and whether this association varies depending on stage of pregnancy and on maternal body mass index (BMI). METHODS: This prospective cohort study included 675 pregnant women followed from 1(st) trimester until delivery. We collected anthropometric measurements, blood samples at 1(st) and 2(nd) trimester, and clinical data until delivery. Maternal leptin was measured by ELISA (Luminex technology). We classified women by BMI measured at 1(st) trimester: BMI < 25 kg/m(2) = normal weight; 25 <= BMI < 30 kg/m(2) = overweight; and BMI >= 30 kg/m(2) = obese. RESULTS: Women gained a mean of 6.7 +/ 3.0 kg between 1(st) and 2(nd) trimester (mid pregnancy GWG) and 5.6 +/- 2.5 kg between 2(nd) and the end of 3(rd) trimester (late pregnancy GWG). Higher 1(st) trimester leptin levels were associated with lower mid pregnancy GWG, but the association was no longer significant after adjusting for % body fat (%BF; beta = 0.38 kg per log-leptin; SE = 0.52; P = 0.46). Higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG and this association remained significant after adjustment for BMI (beta = 2.35; SE = 0.41; P < 0.0001) or %BF (beta = 2.01; SE = 0.42; P < 0.0001). In BMI stratified analyses, higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG in normal weight women (beta = 1.33; SE = 0.42; P =0.002), and this association was stronger in overweight women (beta = 2.85; SE = 0.94; P = 0.003- P for interaction = 0.05). CONCLUSIONS: Our results suggest that leptin may regulate weight gain differentially at 1(st) versus 2(nd) trimester of pregnancy: at 2(nd) trimester, higher leptin levels were associated with greater subsequent weight gain--the opposite of its physiologic regulation in non-pregnancy--and this association was stronger in overweight women. We suspect the existence of a feed-forward signal from leptin in second half of pregnancy, stimulating a positive energy balance and leading to greater weight gain. PMID- 27004423 TI - Clinical safety and effectiveness evaluation of a new antimicrobial wound dressing designed to manage exudate, infection and biofilm. AB - The objective of this work was to evaluate the safety and effectiveness of a next generation antimicrobial wound dressing (NGAD; AQUACEL(r) Ag+ ExtraTM dressing) designed to manage exudate, infection and biofilm. Clinicians were requested to evaluate the NGAD within their standard protocol of care for up to 4 weeks, or as long as deemed clinically appropriate, in challenging wounds that were considered to be impeded by suspected biofilm or infection. Baseline information and post evaluation dressing safety and effectiveness data were recorded using standardised evaluation forms. This data included wound exudate levels, wound bed appearance including suspected biofilm, wound progression, skin health and dressing usage. A total of 112 wounds from 111 patients were included in the evaluations, with a median duration of 12 months, and biofilm was suspected in over half of all wounds (54%). After the introduction of the NGAD, exudate levels had shifted from predominantly high or moderate to low or moderate levels, while biofilm suspicion fell from 54% to 27% of wounds. Wound bed coverage by tissue type was generally shifted from sloughy or suspected biofilm towards predominantly granulation tissue after the inclusion of the NGAD. Stagnant (65%) and deteriorating wounds (27%) were shifted to improved (65%) or healed wounds (13%), while skin health was also reported to have improved in 63% of wounds. High levels of clinician satisfaction with the dressing effectiveness and change frequency were accompanied by a low number of dressing-related adverse events (n = 3; 2.7%) and other negative observations or comments. This clinical user evaluation supports the growing body of evidence that the anti-biofilm technology in the NGAD results in a safe and effective dressing for the management of a variety of challenging wound types. PMID- 27004425 TI - Antiviral response and resistance analysis of treatment-naive HCV-infected patients receiving single and multiple doses of GS-9190. AB - GS-9190 is a NS5B non-nucleoside analogue with demonstrated effectiveness in a Phase 1 monotherapy study and in combination with other DAAs for treatment of chronic HCV infection. Here, the resistance profile of GS-9190 monotherapy in a Phase 1b study was investigated. Resistance analysis was performed by population sequencing and allele-specific PCR (AS-PCR) for Y448H with an assay cut-off of 0.5%. Phenotypic susceptibility analyses were performed on patient isolates as well as site-directed mutagenesis of mutations selected during monotherapy. No resistance-associated variants were observed in patients before or after receiving single doses of GS-9190 by population sequencing. In contrast, in patients who received GS-9190 for 8 days, mutations Y448H and Y452H in NS5B were observed by population sequencing in 21/36 (58%) and 2/36 (5.6%) patients, respectively, at Day 8 or Day 14. Among the remaining 15 patients who had no detectable Y448H at Day 8 or Day 14 by population sequencing, low frequencies of Y448H ranging from 1.3 to 9.7% were detected in 14 of 15 patients by AS-PCR. By AS-PCR, Y448H remained detectable at reduced frequency in the majority of patients analysed through 4-6 months of follow-up. Chimeric HCV replicons constructed with the NS5B sequence from patients with Y448H and Y448H + Y452H/Y demonstrated 27-fold and 78.5-fold reduced susceptibility to GS-9190. In conclusion, Y448H was rapidly selected in the majority of patients receiving multiple doses of GS-9190 as monotherapy, despite undetectable levels in pretreatment samples. Y448H confers reduced susceptibility to GS-9190 and other NNIs and persisted in most patients for months post-treatment. PMID- 27004424 TI - FabR regulates Salmonella biofilm formation via its direct target FabB. AB - BACKGROUND: Biofilm formation is an important survival strategy of Salmonella in all environments. By mutant screening, we showed a knock-out mutant of fabR, encoding a repressor of unsaturated fatty acid biosynthesis (UFA), to have impaired biofilm formation. In order to unravel how this regulator impinges on Salmonella biofilm formation, we aimed at elucidating the S. Typhimurium FabR regulon. Hereto, we applied a combinatorial high-throughput approach, combining ChIP-chip with transcriptomics. RESULTS: All the previously identified E. coli FabR transcriptional target genes (fabA, fabB and yqfA) were shown to be direct S. Typhimurium FabR targets as well. As we found a fabB overexpressing strain to partly mimic the biofilm defect of the fabR mutant, the effect of FabR on biofilms can be attributed at least partly to FabB, which plays a key role in UFA biosynthesis. Additionally, ChIP-chip identified a number of novel direct FabR targets (the intergenic regions between hpaR/hpaG and ddg/ydfZ) and yet putative direct targets (i.a. genes involved in tRNA metabolism, ribosome synthesis and translation). Next to UFA biosynthesis, a number of these direct targets and other indirect targets identified by transcriptomics (e.g. ribosomal genes, ompA, ompC, ompX, osmB, osmC, sseI), could possibly contribute to the effect of FabR on biofilm formation. CONCLUSION: Overall, our results point at the importance of FabR and UFA biosynthesis in Salmonella biofilm formation and their role as potential targets for biofilm inhibitory strategies. PMID- 27004427 TI - Speeding up antimicrobial susceptibility testing. PMID- 27004426 TI - Male patients require higher optimal effect-site concentrations of propofol during i-gel insertion with dexmedetomidine 0.5 MUg/kg. AB - BACKGROUND: The pharmacokinetics and pharmacodynamics of an anesthetic drug may be influenced by gender. The purpose of this study was to compare effect-site half maximal effective concentrations (EC50) of propofol in male and female patients during i-gel insertion with dexmedetomidine 0.5 MUg/kg without muscle relaxants. METHODS: Forty patients, aged 20-46 years of ASA physical status I or II, were allocated to one of two groups by gender (20 patients per group). After the infusion of dexmedetomidine 0.5 MUg/kg over 2 min, anesthesia was induced with a pre-determined effect-site concentration of propofol by target controlled infusion. Effect-site EC50 values of propofol for successful i-gel insertion were determined using the modified Dixon's up-and-down method. RESULTS: Mean effect site EC50 +/- SD of propofol for successful i-gel insertion was significantly higher for men than women (5.46 +/- 0.26 MUg/ml vs. 3.82 +/- 0.34 MUg/ml, p < 0.01). The EC50 of propofol in men was approximately 40% higher than in women. Using isotonic regression with a bootstrapping approach, the estimated EC50 (95% confidence interval) of propofol was also higher in men [5.32 (4.45-6.20) MUg/ml vs. 3.75 (3.05-4.43) MUg/ml]. The estimated EC95 (95% confidence interval) of propofol in men and women were 5.93 (4.72-6.88) MUg/ml and 4.52 (3.02-5.70) MUg/ml, respectively. CONCLUSIONS: During i-gel insertion with dexmedetomidine 0.5 MUg/kg without muscle relaxant, male patients had higher effect-site EC50 for propofol using Schnider's model. Based on the results of this study, patient gender should be considered when determining the optimal dose of propofol during supraglottic airway insertion. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02268656. Registered August 26, 2014. PMID- 27004428 TI - Prevalence and concordance of high-risk papillomavirus infection in male sexual partners of women diagnosed with high grade cervical lesions. AB - BACKGROUND: Little is known about the characteristics of high-risk papillomavirus (HR-HPV) infection in men. The aims of this cross-sectional study were: (a) to investigate HR-HPV prevalence and genotype distribution in men, sexual partners of women presenting with high-grade cervical intraepithelial neoplasia (HG-CIN), according to epidemiological characteristics, and (b) to assess type-specific concordance between partners. METHODS: A total of 125 men were recruited within the first 6 months after HG-CIN diagnosis of their partner. Samples from the coronal sulcus, glans penis shaft, and scrotum were tested with linear array HPV genotyping assay (Roche Diagnostics, Mannheim, Germany). Type-specific concordance within 120 couples was studied. Epidemiological factors were evaluated by multivariate logistic regression analysis. SPSS 19 (IBM, Chicago, USA). RESULTS: The prevalence of HR-HPV infection in males was 50.4% (63/125). HPV16/53/52/51/66/31 were the most frequent genotypes (24/10.4/9.6/8.8/8/7.2%, respectively). Current smoking was associated with an increased risk for HR-HPV infection in men (38.2% (21/55) vs 60% (42/70), OR 2.4, p=0.025). Among 60 infected couples, 62% shared at least one genotype: 41.7% couples were concordantly HPV16 positive and 18.3% were HPV16 negative (kappa value: 0.21). The proportion of women with the same genotype as their male partner was higher than the proportion of men sharing the same genotype as their female partner: 58.7% (37/63) vs 30.8% (37/120), p<0.0001. CONCLUSIONS: Sexual partners of women with HG-CIN are a significant reservoir and vector of HPV infection, a fact that could contribute to making viral clearance more difficult to achieve in their partners after treatment of their HG-CIN lesions. PMID- 27004429 TI - In vitro activity of a polyhexanide-betaine solution against high-risk clones of multidrug-resistant nosocomial pathogens. AB - OBJECTIVE: To determine the in vitro activity of a polyhexanide-betaine solution against collection strains and multidrug-resistant (MDR) nosocomial isolates, including high-risk clones. METHODS: We studied of 8 ATCC and 21 MDR clinical strains of Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, including the multiresistant high-risk clones. The MICs and MBCs of a 0.1% polyhexanide-0.1% betaine solution were determined by microdilution. For each species, strains with the highest MICs were selected for further experiments. The dilution-neutralization test (PrEN 12054) was performed by incubating bacterial inocula of 106CFU/mL for 1min with undiluted 0.1% polyhexanide-betaine solution. The CFUs were counted after neutralization. Growth curves and time-kill curves at concentrations of 0.25, 1, 4, and 8*MIC, were performed. MICs of recovered strains were determined when regrowth was observed in time-kill studies after 24h of incubation. Strains with reduced susceptibility were selected by serial passage on plates with increasing concentrations of polyhexanide-betaine, and MICs were determined. RESULTS: Polyhexanide-betaine MIC range was 0.5-8mg/L. MBCs equalled or were 1 dilution higher than MICs. The dilution-neutralization method showed total inoculum clearance of all strains. In time-kill curves, no regrowth was observed at 4*MIC, except for S. aureus (8*MIC). Increased MICs were not observed in time-kill curves, or after serial passages after exposure to polyhexanide-betaine. CONCLUSIONS: Polyhexanide-betaine presented bactericidal activity against all MDR clinical isolates tested, including high-risk clones, at significantly lower concentrations and time of activity than those commercially used. PMID- 27004430 TI - Reply to the Letter to the Editor entitled "Bleeding risk assessment and comorbidities in elderly patients with acute coronary syndromes". PMID- 27004431 TI - Unusual cause of central aortic prosthetic regurgitation during transcatheter replacement. AB - Transcatheter aortic valve replacement (TAVR) is an increasingly common procedure for the treatment of aortic stenosis in elderly patients with comorbidities that prevent the use of standard surgery. It has been shown that implantation without aortic regurgitation is related to lower mortality. Mild paravalvular regurgitation is inevitable in some cases due to calcification of the aortic annulus and its usually somewhat elliptical shape. Central regurgitation is less common, but has been associated with valve overdilatation in cases in which reduction of paravalvular regurgitation was attempted after the initial inflation. However, there are no reported cases of central prosthetic aortic regurgitation due to acute LV dysfunction. We report a case in which central aortic regurgitation occurred due to transient ventricular dysfunction secondary to occlusion of the right coronary artery by an embolus. The regurgitation disappeared after thrombus aspiration and normal ventricular function was immediately recovered. PMID- 27004432 TI - A moving target--incorporating knowledge of the spatial ecology of fish into the assessment and management of freshwater fish populations. AB - Freshwater fish move vertically and horizontally through the aquatic landscape for a variety of reasons, such as to find and exploit patchy resources or to locate essential habitats (e.g., for spawning). Inherent challenges exist with the assessment of fish populations because they are moving targets. We submit that quantifying and describing the spatial ecology of fish and their habitat is an important component of freshwater fishery assessment and management. With a growing number of tools available for studying the spatial ecology of fishes (e.g., telemetry, population genetics, hydroacoustics, otolith microchemistry, stable isotope analysis), new knowledge can now be generated and incorporated into biological assessment and fishery management. For example, knowing when, where, and how to deploy assessment gears is essential to inform, refine, or calibrate assessment protocols. Such information is also useful for quantifying or avoiding bycatch of imperiled species. Knowledge of habitat connectivity and usage can identify critically important migration corridors and habitats and can be used to improve our understanding of variables that influence spatial structuring of fish populations. Similarly, demographic processes are partly driven by the behavior of fish and mediated by environmental drivers. Information on these processes is critical to the development and application of realistic population dynamics models. Collectively, biological assessment, when informed by knowledge of spatial ecology, can provide managers with the ability to understand how and when fish and their habitats may be exposed to different threats. Naturally, this knowledge helps to better evaluate or develop strategies to protect the long-term viability of fishery production. Failure to understand the spatial ecology of fishes and to incorporate spatiotemporal data can bias population assessments and forecasts and potentially lead to ineffective or counterproductive management actions. PMID- 27004434 TI - Prenatal Programming of Infant Neurobehaviour in a Healthy Population. AB - BACKGROUND: Identifying the prenatal origins of mental conditions is of increasing interest, yet most studies have focused on high-risk populations and cannot disentangle prenatal and postnatal programming effects. Thus, we examined whether profiles of neurobehaviour indicative of future risk could be identified in healthy 1-3-day-old infants, and examined associations with perinatal risk factors. METHODS: Participants included 627 healthy mothers and term infants from a population-based US cohort. Neurobehaviour was assessed within 24-72 h after delivery with the NICU Network Neurobehavioural Scales (NNNS). A model-based clustering algorithm was used to derive neurobehavioural profiles from NNNS scores. Maternal health histories, pregnancy conditions and behaviours, labour/delivery factors, and infant attributes were examined in relation to the neurobehavioural profiles. RESULTS: Seven discrete neurobehavioural profiles were identified, including one average functioning profile, and two inversely patterned below and above average profiles. Higher pregnancy weight gain (OR 1.44, 95% CI 1.10, 1.88) and birthweight percentiles (OR 1.46, 95% CI 1.10, 1.95) were associated with greater odds of below average newborn neurobehaviour. Above average neurobehaviour was associated with experiencing longer gestations (OR 1.29, 95% CI 1.02, 1.64) and higher 5-min APGAR scores (OR 2.43, 95% CI 1.07, 5.52). Maternal pregnancy alcohol use (OR 0.54, 95% CI 0.33, 0.89), and fetal distress (OR 0.10, 95% CI 0.01, 0.72) were associated with lower likelihood of having average neurobehaviour. CONCLUSION: Distinct profiles of neurobehaviour can be derived in a healthy population of newborns, with different sets of perinatal factors predicting different patterns of neurobehaviour. These findings suggest a potential in utero origin for mental health risk. PMID- 27004433 TI - Pollution by oestrogenic endocrine disruptors and beta-sitosterol in a south western European river (Mira, Portugal). AB - The Mira River is a Portuguese water body widely known for its wilderness and is advertised as one of the less polluted European rivers. On this presumption, the levels of endocrine-disrupting compounds (EDCs) in Mira waters were never measured. However, because environmentalists have claimed that the Mira could be moderately polluted, a range of 17 EDCs were measured not only at the estuary but also along the river. The targeted EDCs included natural and pharmaceutical oestrogens (17beta-oestradiol, oestrone and 17alpha-ethynylestradiol), industrial/household pollutants (octylphenols, nonylphenols and their monoethoxylates and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein) and the phytosterol sitosterol (SITO). For this propose, waters from six sampling sites were taken every 2 months, over a 1-year period (2011), and analysed by gas chromatography-mass spectrometry. Unexpectedly high levels of oestrogens and of industrial/household pollutants were measured at all sampling sites, including those located inside natural protected areas. Indeed, the annual average sum of EDCs was ~57 ng/L for oestrogens and ~1.3 MUg/L for industrial/household chemicals. In contrast, the global average levels of phytoestrogens (~140 ng/L) and of SITO (~295 ng/L) were lower than those reported worldwide. The EDC concentrations were normalised for ethynylestradiol equivalents (EE2eq). In view of these, the oestrogenic load of the Mira River attained ~47 ng/L EE2eq. In addition, phosphates were above legal limits at both spring and summer (>1 mg/L). Overall, data show EDCs at toxicant relevant levels in the Mira and stress the need to monitor rivers that are allegedly less polluted. PMID- 27004435 TI - Effects of substituent branching and chirality on the physical properties of ionic liquids based on cationic ruthenium sandwich complexes. AB - An appropriate understanding of how substituents affect the physical properties of ionic liquids is important for the molecular design of ionic liquids. Toward this end, we investigated how the branching and chirality of substituents affect the physical properties of organometallic ionic liquids. We synthesized a series of ionic liquids bearing a branched or linear alkoxy group with the same number of carbons: [Ru(C5H5)(eta(6)-C6H5OR)]X (rac-[1]X: R = -CH(C2H5)(C6H13), [2]X: R = -CH(C4H9)2, [3]X: R = -C9H19), where X = PF6(-), (SO2F)2N(-), and (SO2CF3)2N(-). rac-[1]X are racemic salts. Salts with less symmetrical substituents tend to maintain the liquid state due to suppression of crystallization; crystallization is completely suppressed in most of the rac-[1]X salts and in some of the [2]X salts, whereas not in [3]X salts. The glass-transition temperatures and viscosities of the salts with branched substituents are greater than those with linear substituents. Chiral resolution of rac-[1][PF6] was performed by chiral chromatography. The melting point of rac-[1][PF6] is much lower than that of the enantiopure salt (chiral-[1][PF6]), which we ascribe to the formation of a conglomerate in the solid state. X-ray structure analysis revealed that the solid salts form layered structures. PMID- 27004436 TI - Genetic mutation analysis at early stages of cell line development using next generation sequencing. AB - A central goal for most biopharmaceutical companies is to reduce the development timeline to reach clinical proof of concept. This objective requires the development of tools that ensure the quality of biotherapeutic material destined for the clinic. Recent advances in high throughput protein analytics provide confidence in our ability to assess productivity and product quality attributes at early stages of cell line development. However, one quality attribute has, until recently, been absent from the standard battery of analytical tests facilitating informed choices early in cell line selection: genetic sequence confirmation. Techniques historically used for mutation analysis, such as detailed mass spectrometry, have limitations on the sample number and turnaround times making it less attractive at early stages. Thus, we explored the utility of Next-Generation Sequencing (NGS) as a solution to address these limitations. Amplicon sequencing is one such NGS technique that is robust, rapid, sensitive, and amenable to multiplexing, all of which are essential attributes for our purposes. Here we report a NGS method based upon amplicon sequencing that has been successfully incorporated into our cell line development workflow alongside other high-throughput protein analytical assays. The NGS method has demonstrated its value by identifying at least one Chinese hamster ovary (CHO) clone expressing a variant form of the biotherapeutic in each of the four clinical programs in which it has been utilized. We believe this sequence confirmation method is essential to safely accelerating the time to clinical proof of concept of biotherapeutics, and guard against delays related to sequence mutations. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:813-817, 2016. PMID- 27004437 TI - Design, Synthesis, and Structure--Activity Relationship of New 2-Aryl-3,4-dihydro beta-carbolin-2-ium Salts as Antifungal Agents. AB - Twenty-two 2-aryl-9-methyl-3,4-dihydro-beta-carbolin-2-ium bromides along with four 9-demethylated derivatives were synthesized and characterized by spectroscopic analysis. By using the mycelium growth rate method, the compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Almost all of the compounds showed obvious inhibition activity on each of the fungi at 150 MUM. For all of the fungi, 10 of the compounds showed average inhibition rates of >80% at 150 MUM, and most of their EC50 values were in the range of 2.0-30.0 MUM. SAR analysis showed that the substitution pattern of the N-aryl ring significantly influences the activity; N9-alkylation improves the activity, whereas aromatization of ring-C reduces the activity. It was concluded that the present research provided a series of new 2-aryl-9-alkyl-3,4-dihydro-beta-carbolin-2-iums with excellent antifungal potency and structure optimization design for the development of new carboline antifungal agents. PMID- 27004439 TI - Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients. AB - BACKGROUND: Gastrointestinal (GI) cytomegalovirus (CMV) disease is the most common manifestation of tissue-invasive CMV infection in solid organ transplant (SOT) recipients, but the diagnostic yields of blood and tissue testing have not been systematically assessed in a large patient cohort. METHODS: We retrospectively identified consecutive SOT recipients with biopsy-confirmed GI CMV disease who had both tissue and blood (CMV polymerase chain reaction or antigenemia) diagnostic testing performed within 14 days of diagnosis. Descriptive statistics and logistic regression were used to assess the association between patient factors and viremia and the diagnostic yield of tests performed on biopsy specimens. RESULTS: A total of 101 patients (73% donor seropositive/recipient seronegative [D+/R-], 22% recipient seropositive [R+]) had GI CMV disease (58% upper, 22% lower, and 20% both) at a median of 185 days (range, 21-6345 days) post transplant. In multivariate analysis, R+ CMV serostatus (odds ratio [OR] 0.1 [0.0-0.4], P < 0.001) and diagnosis >6 months post transplant (OR 0.3 [0.1-0.9], P = 0.03) were each independently associated with absence of CMV viremia at time of diagnosis. In the subset of patients (n = 29) in whom both histopathology and viral culture were performed on biopsy specimens, 11 (39%) had CMV detected only by culture and had similar clinical characteristics and outcomes to those with positive histopathology (P > 0.05 for all comparisons). CONCLUSIONS: The sensitivity of viremia in SOT recipients with GI CMV disease is significantly lower in CMV-seropositive patients and in those >6 months post transplant. Addition of viral culture to endoscopic biopsy specimens significantly increases the diagnostic yield for GI CMV disease. PMID- 27004438 TI - Behaviour of hygrine and cuscohygrine in illicit cocaine production establishes their use as markers for chewing coca leaves in contrast with cocaine abuse. AB - Hygrine (HYG) and cuscohygrine (CUS) are natural alkaloids of coca leaves but are not found in illicit cocaine seizures. Therefore, they were proposed as markers for coca chewing in contrast to cocaine abuse in urine and hair testing. In order to examine at which step of the illegal cocaine production these compounds are lost, coca leaves were processed according to an authentic procedure by extraction with lime and kerosene, re-extraction with sulphuric acid, and precipitation of coca paste with ammonia. Non-extracted and extracted coca leaves, acidic extract and coca paste were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC MS/MS) for cocaine, ecgonine methyl ester (EME), cinnamoylcocaine (CIN), HYG, and CUS. It follows from the results that under these conditions, HYG and CUS are extracted only to a minor extent by kerosene and are not precipitated from the acidic re-extract in the coca paste. Due to this behaviour in illegal cocaine production, they fulfil the conditions as markers for coca chewing in an optimal way. However, for unambiguous discrimination between coca chewing and cocaine abuse in human samples, additional markers of manufactured cocaine are required. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27004440 TI - Gastroschisis outcomes in North America: a comparison of Canada and the United States. AB - BACKGROUND: Care of infants with gastroschisis is centralized in Canada and noncentralized in the United States. We conducted an outcomes comparison between the two countries and analyzed the determinants of such outcomes. METHODS: Inpatient mortality and hospital stay of gastroschisis patients from the Canadian Pediatric Surgery Network prospective clinical database for the period 2005-2013 were compared with those from the US Kids Inpatient Database for the period 2003 2012. Potential outcome determinants were analyzed using univariate and multivariate analyses. RESULTS: A comparison was made between 695 Canadian patients and 5216 American patients. Complex gastroschisis was found in 16.0% and 13.7% of patients in Canada and the US, respectively; P=0.11. Canada had less premature births, more normal birth weight (BW) infants, less cesarean section deliveries, and more inborn patients compared to the US. For simple gastroschisis, Canadian mortality was lower (1.4% vs. 3.4%; P=.008) and hospital stay was longer (45+/-38 vs. 41+/-32days; P=.04). US mortality correlated strongly with low BW (P=.002) and marginally with cesarean section delivery (P=.08). A longer Canadian hospital stay was associated with lower gestational age (P=0.01) and western region (P=0.04), while a longer American hospital stay was associated with medium neonatal intensive care unit gastroschisis volume (P=.03), low socioeconomic status (P=.06), low BW (P=0.06), and public insurance (P=0.07). Outcomes for complex gastroschisis did not differ between Canada and the US. CONCLUSIONS: Mortality for simple gastroschisis is higher in the US than in Canada, whereas no outcome differences exist for complex gastroschisis. Outcome determinants are different between the 2 countries. PMID- 27004441 TI - Banana fruit VQ motif-containing protein5 represses cold-responsive transcription factor MaWRKY26 involved in the regulation of JA biosynthetic genes. AB - Most harvested fruits and vegetables are stored at low temperature but many of them are highly sensitive to chilling injury. Jasmonic acid (JA), a plant hormone associated with various stress responses, is known to reduce chilling injury in fruits. However, little is known about the transcriptional regulation of JA biosynthesis in relation to cold response of fruits. Here, we show the involvement of a Group I WRKY transcription factor (TF) from banana fruit, MaWRKY26, in regulating JA biosynthesis. MaWRKY26 was found to be nuclear localized with transcriptional activation property. MaWRKY26 was induced by cold stress or by methyl jasmonate (MeJA), which enhances cold tolerance in banana fruit. More importantly, MaWRKY26 transactivated JA biosynthetic genes MaLOX2, MaAOS3 and MaOPR3 via binding to their promoters. Further, MaWRKY26 physically interacted with a VQ motif-containing protein MaVQ5, and the interaction attenuated MaWRKY26-induced transactivation of JA biosynthetic genes. These results strongly suggest that MaVQ5 might act as a repressor of MaWRKY26 in activating JA biosynthesis. Taken together, our findings provide new insights into the transcriptional regulation of JA biosynthesis in response to cold stress and a better understanding of the molecular aspects of chilling injury in banana fruit. PMID- 27004442 TI - Challenging nickel-catalysed amine arylations enabled by tailored ancillary ligand design. AB - Palladium-catalysed C(sp(2))-N cross-coupling (that is, Buchwald-Hartwig amination) is employed widely in synthetic chemistry, including in the pharmaceutical industry, for the synthesis of (hetero)aniline derivatives. However, the cost and relative scarcity of palladium provides motivation for the development of alternative, more Earth-abundant catalysts for such transformations. Here we disclose an operationally simple and air-stable ligand/nickel(II) pre-catalyst that accommodates the broadest combination of C(sp(2))-N coupling partners reported to date for any single nickel catalyst, without the need for a precious-metal co-catalyst. Key to the unprecedented performance of this pre-catalyst is the application of the new, sterically demanding yet electron-poor bisphosphine PAd-DalPhos. Featured are the first reports of nickel-catalysed room temperature reactions involving challenging primary alkylamine and ammonia reaction partners employing an unprecedented scope of electrophiles, including transformations involving sought-after (hetero)aryl mesylates for which no capable catalyst system is known. PMID- 27004443 TI - Role of bone scan in addition to CT in patients with breast cancer selected for systemic staging. AB - BACKGROUND: The majority of women with breast cancer present with localized disease. The optimal strategy for identifying patients with metastatic disease at diagnosis remains unclear. The aim of this study was to evaluate the additional diagnostic yield from isotope bone scanning when added to CT staging of the thorax, abdomen and pelvis (CT-TAP) in patients with newly diagnosed breast cancer. METHODS: All patients diagnosed with breast cancer who underwent staging CT-TAP and bone scan between 2011 and 2013 were identified from a prospective database of a tertiary referral breast cancer centre that provides a symptomatic and population-based screening breast service. Criteria for staging included: biopsy-proven axillary nodal metastases; planned neoadjuvant chemotherapy or mastectomy; locally advanced or inflammatory breast cancer and symptoms suggestive of metastases. RESULTS: A total of 631 patients underwent staging by CT-TAP and bone scan. Of these, 69 patients (10.9 per cent) had distant metastasis at presentation, with disease confined to a single organ in 49 patients (71 per cent) and 20 (29 per cent) having metastatic deposits in multiple organs. Bone metastasis was the most common site; 39 of 49 patients had bone metastasis alone and 12 had a single isolated metastatic deposit. All but two of these were to the axial skeleton. No preoperative histological factors identified a cohort of patients at risk of metastatic disease. Omission of the bone scan in systemic staging would have resulted in a false-negative rate of 0.8 per cent. CONCLUSION: For patients diagnosed with breast cancer, CT-TAP is a satisfactory stand-alone investigation for systemic staging. PMID- 27004445 TI - Real-Time Monitoring of Chemical and Topological Rearrangements in Solidifying Amphiphilic Polymer Co-Networks: Understanding Surface Demixing. AB - Amphiphilic polymer co-networks provide a unique route to integrating contrasting attributes of otherwise immiscible components within a bicontinuous percolating morphology and are anticipated to be valuable for applications such as biocatalysis, sensing of metabolites, and dual dialysis membranes. These co networks are in essence chemically forced blends and have been shown to selectively phase-separate at surfaces during film formation. Here, we demonstrate that surface demixing at the air-film interface in solidifying polymer co-networks is not a unidirectional process; instead, a combination of kinetic and thermodynamic interactions leads to dynamic molecular rearrangement during solidification. Time-resolved gravimetry, low contact angles, and negative out-of-plane birefringence provided strong experimental evidence of the transitory trapping of thermodynamically unfavorable hydrophilic moieties at the air-film interface due to fast asymmetric solvent depletion. We also find that slow-drying hydrophobic elements progressively substitute hydrophilic domains at the surface as the surface energy is minimized. These findings are broadly applicable to common-solvent bicontinuous systems and open the door for process controlled performance improvements in diverse applications. Similar observations could potentially be coupled with controlled polymerization rates to maximize the intermingling of bicontinuous phases at surfaces, thus generating true three dimensional, bicontinuous, and undisturbed percolation pathways throughout the material. PMID- 27004444 TI - Clinical Impact of Heparin Kinetics During Catheter Ablation of Atrial Fibrillation: Meta-Analysis and Meta-Regression. AB - INTRODUCTION: Appropriate activated clotting time (ACT) during catheter ablation of atrial fibrillation (CA-AF) is essential to minimize periprocedural complications. METHODS AND RESULTS: An electronic search was performed using major databases. Outcomes were thromboembolic (TE) and bleeding complications according to ACT levels (seconds). Heparin dose (U/kg) and time (minutes) to achieve the target ACT was compared among patients receiving vitamin K antagonist (VKA) versus non-VKA oral anticoagulants (NOAC). Nineteen studies involving 7,150 patients were identified. Patients with ACT > 300 had less TE (OR, 0.51; 95% CI 0.35-0.74) and bleeding (OR, 0.70; 95% CI 0.60-0.83) compared to ACT < 300, when using any type of oral anticoagulation. The use of VKA was associated with reduced heparin requirements (mean dose: 157 U/kg vs. 209 U/kg, P < 0.03; SDM 0.86 [95% CI -1.39 to -0.33]), and with lower time to achieve the target ACT (mean time: 24 minutes vs. 49 minutes, P < 0.03; SDM -11.02 [95% CI -13.29 to 8.75]) compared to NOACs. No significant publication bias was found. CONCLUSIONS: Performing CA-AF with a target ACT > 300 decreases the risk of TE without increasing the risk of bleeding. Patients receiving VKAs required less heparin and reached the target ACT faster compared to NOACs. PMID- 27004447 TI - Miniature Compressive Ultra-spectral Imaging System Utilizing a Single Liquid Crystal Phase Retarder. AB - Spectroscopic imaging has been proved to be an effective tool for many applications in a variety of fields, such as biology, medicine, agriculture, remote sensing and industrial process inspection. However, due to the demand for high spectral and spatial resolution it became extremely challenging to design and implement such systems in a miniaturized and cost effective manner. Using a Compressive Sensing (CS) setup based on a single variable Liquid Crystal (LC) retarder and a sensor array, we present an innovative Miniature Ultra-Spectral Imaging (MUSI) system. The LC retarder acts as a compact wide band spectral modulator. Within the framework of CS, a sequence of spectrally modulated images is used to recover ultra-spectral image cubes. Using the presented compressive MUSI system, we demonstrate the reconstruction of gigapixel spatio-spectral image cubes from spectral scanning shots numbering an order of magnitude less than would be required using conventional systems. PMID- 27004446 TI - Imprinted genes and imprinting control regions show predominant intermediate methylation in adult somatic tissues. AB - Genomic imprinting is an epigenetic feature characterized by parent-specific monoallelic gene expression. The aim of this study was to compare the DNA methylation status of imprinted genes and imprinting control regions (ICRs), harboring differentially methylated regions (DMRs) in a comprehensive panel of 18 somatic tissues. The germline DMRs analyzed were divided into ubiquitously imprinted and placenta-specific DMRs, which show identical and different methylation imprints in adult somatic and placental tissues, respectively. We showed that imprinted genes and ICR DMRs maintain methylation patterns characterized by intermediate methylation levels in somatic tissues, which are pronounced in a specific region of the promoter area, located 200-1500 bp from the transcription start site. This intermediate methylation is concordant with gene expression from a single unmethylated allele and silencing of a reciprocal parental allele through DNA methylation. The only exceptions were seen for ICR DMRs of placenta-specific imprinted genes, which showed low levels of methylation, suggesting that these genes escape parent-specific epigenetic regulation in somatic tissues. PMID- 27004448 TI - Value-added processing of crude glycerol into chemicals and polymers. AB - Crude glycerol is a low-value byproduct which is primarily obtained from the biodiesel production process. Its composition is significantly different from that of pure glycerol. Crude glycerol usually contains various impurities, such as water, methanol, soap, fatty acids, and fatty acid methyl esters. Considerable efforts have been devoted to finding applications for converting crude glycerol into high-value products, such as biofuels, chemicals, polymers, and animal feed, to improve the economic viability of the biodiesel industry and overcome environmental challenges associated with crude glycerol disposal. This article reviews recent advances of biological and chemical technologies for value-added processing of crude glycerol into chemicals and polymers, and provides strategies for addressing production challenges. PMID- 27004449 TI - Reversible Photoresponsive Molecular Alignment of Liquid Crystals at Fluid Interfaces with Persistent Stability. AB - This work demonstrates a noninvasive approach to control alignment of liquid crystals persistently and reversibly at fluid interfaces by using a photoresponsive azobenzene-based surfactant dissolved in an ionic liquid (IL), ethylammonium nitrate (EAN). As the first report on the orientational behavior of LCs at the IL/LC interface, our study also expands current understanding of alignment control of LCs at the aqueous/LC interface by adding electrolytes into aqueous solutions. The threshold concentration for switching the optical responses of LCs can be changed just by simply manipulating the ratio of EAN to H2 O. This work will inspire fundamental studies and novel applications of using the LC-based imaging technique to investigate various chemical and biological events in ILs. PMID- 27004450 TI - The impact of intolerance of emotional distress and uncertainty on veterans with co-occurring PTSD and substance use disorders. AB - The risk of developing a substance use disorder (SUD) is significantly higher among veterans with posttraumatic stress disorder (PTSD). Veterans with this co occurrence have poorer outcomes than singly diagnosed veterans, which may be related to two risk factors: intolerance uncertainty (IU) and low tolerance of emotional distress (TED). We hypothesized low TED and high IU would independently and interactively relate to heightened PTSD symptomatology and trauma-cue elicited SUD cravings. A sample of 70 veterans (M age=50; 95% men; 65% Black) with co-occurring PTSD-SUD was recruited. The Posttraumatic Stress Disorder Checklist (PCL), Craving Questionnaire, Distress Tolerance Scale, and Intolerance of Uncertainty Scale were administered. In general, low TED and high IU were significantly correlated with the PCL total and subscale scores. When examined within regression models, low TED was associated with elevated PCL scores and trauma-cue elicited SUD cravings; IU was not. However, there was a significant interaction between IU and TED; veterans with elevated IU and low TED had higher PCL Total, Hyperarousal, and Intrusions scores. This highlights the importance of assessing TED and IU among veterans with co-occurring PTSD-SUD, as these risk factors may not only be prognostic indicators of outcomes, but also treatment targets. PMID- 27004451 TI - Prevalence of antibodies against Borrelia burgdorferi, Anaplasma phagocytophilum, and Leptospira interrogans serovars in Bernese Mountain Dogs. AB - OBJECTIVE: Bernese Mountain Dogs (BMD) have a higher prevalence of Borrelia burgdorferi sensu lato (Bbsl) antibodies than other breeds, but it is not known whether this is the case for other pathogens. Therefore, the aim of the study was to determine the frequency and level of specific antibodies against members of the Bbsl group, Anaplasma phagocytophilum (Ap), and Leptospira (L.) interrogans serovars in BMD and compare the results with those found in dogs of other breeds. MATERIALS AND METHODS: A total of 171 healthy BMD and 57 healthy control dogs of other breeds were included in the study. Controls were large dogs (> 30 kg) with long, dark hair coats. A two-tiered testing method consisting of computerized kinetic enzyme-linked immunosorbent assay (KELA) and Western blotting was used for detection of antibodies against Bbsl, an immunofluorescence assay (IFA) was used for detection of antibodies against Ap, and microscopic agglutination test (MAT) for antibodies to 18 different serovars of L. interrogans. RESULTS: The prevalence of anti-Bbsl antibodies was significantly higher in BMD (43.3%) than in controls (17.5%) (p < 0.001). Antibodies to Bbsl attributable to vaccination were excluded from the calculation of prevalence. Antibodies to Ap were found in 50.3% of BMD, whereas only 24.6% of the controls dogs were tested positive for Ap (p < 0.001). Antibody titers of the 18 different serovars of L. interrogans antibodies did not differ significantly between BMD and control dogs except for L. copenhageni antibody titers which were higher in BMD. Significantly higher antibody titers to L. canicola (p = 0.003), L. copenhageni (p = 0.005), L. grippothyphosa (p = 0.029) and L. vanderhoedoni (p = 0.035) were seen in BMD compared to control dogs. CONCLUSION AND CLINICAL RELEVANCE: BMD had a higher prevalence of anti-Bbsl, anti-L. copenhageni and anti-Ap antibodies than control dogs. Significantly higher antibody titers against L. canicola (p = 0.003), L. copenhageni (p = 0.005), L. grippothyphosa (p = 0.029) and L. vanderhoedoni (p = 0.035) were seen in BMD compared with control dogs, but the reason for this and potential clinical implications are not known. PMID- 27004452 TI - Are aryl hydrocarbon receptor and G-protein-coupled receptor 30 involved in the regulation of seasonal testis activity in photosensitive rodent-the bank vole (Myodes glareolus)? AB - Within the reproductive system both aryl hydrocarbon receptor (AHR) and G-protein coupled receptor 30 (GPR30) contribute to estrogen signaling and controlling of reproductive physiology. The specific question is whether and how AHR and GPR30 are involved in regulation of testis function in seasonally breeding rodents. Bank vole testes were obtained from animals reared under 18 hours light:6 hours dark (LD) and 6 hours light:18 hours dark (SD) conditions. Aryl hydrocarbon receptor and GPR30 expression were analyzed by quantitative reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry and/or immunofluorescent staining. In addition, the activity of enzymes involved in the intracellular signal transduction; extracellular signal-regulated kinase (ERK), protein kinase (PKA), matrix metalloproteinase 9 (MMP 9) and the concentrations of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and calcium (Ca(2+)) were examined by immunohistochemical, immunoenzymatic, and colorimetric assays, respectively. Aryl hydrocarbon receptor and GPR30 were expressed in testes of actively reproducing voles and regressed ones although their expression at the messenger RNA and AHR also at protein level appeared to be photoperiod-dependent. A specific cellular localization and expression of AHR and GPR30 correlated with the expression of ERK, PKA, and MMP 9. Moreover, we found robust differences in the levels of cAMP, cGMP, and Ca(2+) in testicular homogenates between LD and SD voles. In the testes of LD voles, the levels of second messengers were always higher compared to SD. In vole testis, AHR and GPR30 can induce signaling pathways that involve ERK, PKA, MMP 9 and cAMP, cGMP, Ca(2+). In addition, in AHR, signaling the engagement of both photoperiod and estrogens, whereas in GPR30, signaling only estrogens is reported. It is likely that in vole, because of a differential activity of signaling molecules, signal transduction via AHR rather than through GPR30 plays a role in regulation of seasonal changes of testis physiology. PMID- 27004453 TI - Perceptions of other integrative health therapies by Veterans with pain who are receiving massage. AB - Veterans are increasingly using complementary and integrative health (CIH) therapies to manage chronic pain and other troubling symptoms that significantly impair health and quality of life. The Department of Veterans Affairs (VA) is exploring ways to meet the demand for access to CIH, but little is known about Veterans' perceptions of the VA's efforts. To address this knowledge gap, we conducted interviews of 15 inpatients, 8 receiving palliative care, and 15 outpatients receiving CIH in the VA. Pain was the precipitating factor in all participants' experience. Participants were asked about their experience in the VA and their opinions about which therapies would most benefit other Veterans. Participants reported that massage was well-received and resulted in decreased pain, increased mobility, and decreased opioid use. Major challenges were the high ratio of patients to CIH providers, the difficulty in receiving CIH from fee based CIH providers outside of the VA, cost issues, and the role of administrative decisions in the uneven deployment of CIH across the VA. If the VA is to meet its goal of offering personalized, proactive, patient-centered care nationwide then it must receive support from Congress while considering Veterans' goals and concerns to ensure that the expanded provision of CIH improves outcomes. PMID- 27004454 TI - From morphology to biochemical state - intravital multiphoton fluorescence lifetime imaging of inflamed human skin. AB - The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients' bedsides. These 'optical biopsies' generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy. PMID- 27004455 TI - Trisomy 3 mosaicism in a 5-year-old boy with multiple anomalies: A very rare case. AB - Trisomy 3 mosaicism in live birth is exceedingly rare. In this study, we report a 5-year-old boy with trisomy 3 mosaicism who exhibits skeletal anomalies, atypical form of ectodermal dysplasias, refractory diarrhea, and normal intelligence. Fluorescence in situ hybridization and microsatellite marker analyses confirmed the existence of trisomy 3 mosaicism and suggested that the parental origin of the additional chromosome 3 in the trisomic cells was maternal. This report further delineated the trisomy 3 mosaicism in live births. The authors propose that both common phenotypes and phenotypic diversity exist on cases with trisomy 3 mosaicism. (c) 2016 Wiley Periodicals, Inc. PMID- 27004456 TI - Near infrared fluorescent biliproteins generated from bacteriophytochrome AphB of Nostoc sp. PCC 7120. AB - The genome of the cyanobacterium Nostoc sp. PCC 7120 encodes a large number of putative bacteriophytochrome and cyanobacteriochrome photoreceptors that, due to their long-wavelength absorption and fluorescence emission, might serve as fluorescent tags in intracellular investigations. We show that the PAS-GAF domain of the bacteriophytochrome, AphB, binds biliverdin covalently and exhibits, besides its reversible photochemistry, a moderate fluorescence in the near infrared (NIR) spectral region. It was selected for further increasing the brightness while retaining the NIR fluorescence. In the first step, amino acids assumed to improve fluorescence were selectively mutated. The resulting variants were then subjected to several rounds of random mutagenesis and screened for enhanced fluorescence in the NIR. The brightness of optimized PAS-GAF variants increased more than threefold compared to that of wt AphB(1-321), with only insignificant spectral shifts (Amax around 695 nm, and Fmax around 720 nm). In general, the brightness increases with decreasing wavelengths, which allows for a selection of the fluorophore depending on the optical properties of the tissue. A spectral heterogeneity was observed when residue His260, located in close proximity to the chromophore, was mutated to Tyr, emphasizing the strong effects of the environment on the electronic properties of the bound biliverdin chromophore. PMID- 27004458 TI - Nanostructured surfaces investigated by quantitative morphological studies. AB - The morphology of different surfaces has been investigated by atomic force microscopy and quantitatively analyzed in this paper. Two different tools have been employed to this scope: the analysis of the height-height correlation function and the determination of the mean grain size, which have been combined to obtain a complete characterization of the surfaces. Different materials have been analyzed: SiO(x)N(y), InGaN/GaN quantum wells and Si nanowires, grown with different techniques. Notwithstanding the presence of grain-like structures on all the samples analyzed, they present very diverse surface design, underlying that this procedure can be of general use. Our results show that the quantitative analysis of nanostructured surfaces allows us to obtain interesting information, such as grain clustering, from the comparison of the lateral correlation length and the grain size. PMID- 27004457 TI - Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden. AB - Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61 3.50. Stage III-IV vs I: OR = 2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. The CMM specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95% CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis. PMID- 27004459 TI - Guideline authors' response to Dr Saper's idiopathic normal pressure hydrocephalus commentary. PMID- 27004460 TI - Revisiting the thermodynamic modelling of type I gas-hydroquinone clathrates. AB - Under specific pressure and temperature conditions, certain gaseous species can be engaged in a host lattice of hydroquinone molecules, forming a supramolecular entity called a gas hydroquinone clathrate. This study is devoted to the thermodynamic modelling of type I hydroquinone clathrates. The gases considered in this work are argon, krypton, xenon, methane, nitrogen, oxygen and hydrogen sulphide. The basic van der Waals and Platteeuw model, which is, for example, not able to predict well the phase equilibrium properties of such clathrates at high temperature, is modified and extended by considering first the solubility of the guest in solid HQ and then the mutual interactions between the gaseous molecules inside the clathrate structure (i.e. guest-guest interactions). Other improvements of the basic theory, such as the choice of the reference state, are proposed, and a unique set of thermodynamic parameters valid for all the studied guests are finally calculated. Very good agreement is obtained between the model predictions and the experimental data available in the literature. Our results clearly demonstrate that the highest level of theory is necessary to describe well both the triphasic equilibrium line (where the HQ clathrate, the native hydroquinone HQalpha and the gas coexist), the occupancy of the guest in the clathrate, and the intercalation enthalpy. PMID- 27004461 TI - Structural biology of intrinsically disordered proteins: Revisiting unsolved mysteries. AB - The emergence of intrinsically disordered proteins (IDPs) has challenged the classical protein structure-function paradigm by introducing a new paradigm of "coupled binding and folding". This paradigm suggests that IDPs fold upon binding to their partners. Further studies, however, revealed a novel and previously unrecognized phenomenon of "uncoupled binding and folding" suggesting that IDPs do not necessarily fold upon interaction with their lipid and protein partners. The complex and often unusual biophysics of IDPs makes structural characterization of these proteins and their complexes not only challenging but often resulting in opposite conclusions. For this reason, some crucial questions in this field remain unsolved for well over a decade. Considering an important role of IDPs in cellular regulation, signaling and control in health and disease, more efforts are needed to solve these mysteries. Here, I focus on two long standing contradictions in the literature concerning dimerization and membrane binding activities of IDPs. Molecular explanation of these discrepancies is provided. I also demonstrate how resolution of these critical issues in the field of IDPs results in our expanded understanding of cell function and has multiple applications in biology and medicine. PMID- 27004462 TI - Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial. AB - Cholesterol elevations are associated with systemic inflammation and endothelial fragmentation into microparticles. The cholesterol-lowering efficacy of nutraceutical combinations (NC) has not been investigated in patients with low grade systemic inflammation and normal-borderline cholesterol levels. This is a 3 month prospective randomized open-label interventional study in patients with elevated plasma high sensitivity C-reactive protein (hsCRP) levels (>2 mg/L) and low-density lipoprotein (LDL) cholesterol of 100-160 mg/dL. The effect of either an oral cholesterol-lowering nutraceutical combination (NC) or no active treatment (noNC) was tested on LDL cholesterol, hsCRP and endothelial microparticle (EMPs) levels. Patients taking the NC had a significant reduction of total (-12%) and LDL cholesterol (-23%) compared to those who received noNC (p < 0.001 for both). Also, hsCRP and EMPs were significantly reduced by the NC ( 41% and -16%, respectively). LDL cholesterol change was positively associated with hsCRP (rho = 0.21, p = 0.04) and EMP changes (rho = 0.56, p < 0.001), hsCRP and EMP changes being associated with each other (rho = 0.28, p = 0.005). Patients experiencing both LDL cholesterol and hsCRP reduction were those having the greatest EMP decrease. In conclusion, among patients with low-grade systemic inflammation, an oral NC significantly improved cholesterol profile and attenuated the degree of systemic inflammation and endothelial injury. PMID- 27004463 TI - Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive. AB - Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson's disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model. PMID- 27004464 TI - Cloning of chrysanthemum high-affinity nitrate transporter family (CmNRT2) and characterization of CmNRT2.1. AB - The family of NITRATE TRANSPORTER 2 (NRT2) proteins belongs to the high affinity transport system (HATS) proteins which acts at low nitrate concentrations. The relevant gene content of the chrysanthemum genome was explored here by isolating the full length sequences of six distinct CmNRT2 genes. One of these (CmNRT2.1) was investigated at the functional level. Its transcription level was inducible by low concentrations of both nitrate and ammonium. A yeast two hybrid assay showed that CmNRT2.1 interacts with CmNAR2, while a BiFC assay demonstrated that the interaction occurs at the plasma membrane. Arabidopsis thaliana plants heterologously expressing CmNRT2.1 displayed an enhanced rate of labeled nitrogen uptake, suggesting that CmNRT2.1 represents a high affinity root nitrate transporter. PMID- 27004465 TI - Development and evaluation of a spatial decision support system for malaria elimination in Bhutan. AB - BACKGROUND: Bhutan has reduced its malaria incidence significantly in the last 5 years, and is aiming for malaria elimination by 2016. To assist with the management of the Bhutanese malaria elimination programme a spatial decision support system (SDSS) was developed. The current study aims to describe SDSS development and evaluate SDSS utility and acceptability through informant interviews. METHODS: The SDSS was developed based on the open-source Quantum geographical information system (QGIS) and piloted to support the distribution of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in the two sub-districts of Samdrup Jongkhar District. It was subsequently used to support reactive case detection (RACD) in the two sub-districts of Samdrup Jongkhar and two additional sub-districts in Sarpang District. Interviews were conducted to ascertain perceptions on utility and acceptability of 11 informants using the SDSS, including programme and district managers, and field workers. RESULTS: A total of 1502 households with a population of 7165 were enumerated in the four sub-districts, and a total of 3491 LLINs were distributed with one LLIN per 1.7 persons. A total of 279 households representing 728 residents were involved with RACD. Informants considered that the SDSS was an improvement on previous methods for organizing LLIN distribution, IRS and RACD, and could be easily integrated into routine malaria and other vector-borne disease surveillance systems. Informants identified some challenges at the programme and field level, including the need for more skilled personnel to manage the SDSS, and more training to improve the effectiveness of SDSS implementation and use of hardware. CONCLUSIONS: The SDSS was well accepted and informants expected its use to be extended to other malaria reporting districts and other vector-borne diseases. Challenges associated with efficient SDSS use included adequate skills and knowledge, access to training and support, and availability of hardware including computers and global positioning system receivers. PMID- 27004466 TI - Parameter identification using stochastic simulations reveals a robustness in CD95 apoptotic response. AB - A number of mathematical models of apoptosis generated recently allowed us to understand intrinsic mechanisms of life/death decisions in a cell. Nevertheless, the parameters for the mathematical models are often experimentally difficult to obtain and there is an emerging need for the development of efficient approaches for parameter estimation. In this study we suggest a new method for parameter estimation, which is based on stochastic simulations and can be used when the number of molecules in the system is small. Our approach comprised the following steps: we start from the selection of parameters that lead to a good ordinary differential equation (ODE) fit. We continued by carrying out stochastic simulations for each of these parameters. Comparing the correlation structure of these simulations with the data, we finally could identify the best parameter set. The method was applied for a model of CD95-induced apoptosis, the new best identified parameters fit well to the experimental data. The best parameter set allowed us to get new insights into CD95 apoptosis regulation and can be applied for the comprehensive analysis of other signaling networks. The modeling approach allowed us to get new insights into network regulation, in particular, to identify robustness in CD95 apoptotic response. Taken together, this new method provides valuable predictions and can be applied for the analysis of other signaling networks. PMID- 27004467 TI - CYP21A2 expression is localized in the developing distal epithelium of the human perinatal lung and is compatible with in situ production and intracrine actions of active glucocorticoids. AB - Glucocorticoids play essential roles in lung development. We investigated for expression of CYP21A2 (21-hydroxylase) as well as for the presence of the corresponding protein and identification of CYP21A2-expressing cells in several human developing lungs. Expression of some related genes was also assessed. CYP21A2 and CYP17A1 (P450c17) mRNAs were found in all the 34 lung samples from 17 to 40 weeks' gestation at variable levels. No correlation was found according to sex but a correlation with age was detected for CYP17A1 only. In contrast, CYP11B1 (11beta-hydroxylase)- and CYP11B2 (aldosterone synthase)-mRNAs were not detected. Significant levels of the CYP21A2 protein were detected in all the analyzed samples, while only very low signals were detected for CYP17A1 protein. In situ hybridization revealed that CYP21A2 was almost exclusively expressed in the distal epithelium. It was reported that the lung distal epithelium of human fetuses also express 11beta-hydroxysteroid dehydrogenase type 2, which catalyzes cortisol inactivation into cortisone. Based on this information, intracrine glucocorticoid actions should take place from CYP21A2 products through the glucocorticoid receptor in the absence of cortisol. In contrast, mineralocorticoid receptor activation did not seem to depend on deoxycorticosterone produced from local activity of CYP21A2 because of the reported circulating amounts of aldosterone. PMID- 27004468 TI - Effects of (+)-usnic acid and (+)-usnic acid-liposome on Toxoplasma gondii. AB - Toxoplasma gondii pathogen is a threat to human health that results in economic burden. Unfortunately, there are very few high-efficiency and low-toxicity drugs for toxoplasmosis in the clinic. (+)-Usnic acid derived from lichen species has been reported to have anti-inflammatory, antibacterial, anti-parasitology, and even anti-cancer activities. Herein, the systematic effect of (+)-usnic acid and (+)-usnic acid-liposome on toxoplasma were studied in vitro and in vivo. The viability of toxoplasma tachyzoite was assayed with trypan blue and Giemsa staining; while the invasive capability of tachyzoite to cardiofibroblasts was detected using Giemsa staining. The survival time of mice and the changes in tachyzoite ultrastructure were studied in vivo. The results showed that (+)-usnic acid inhibited the viability of tachyzoite; pretreatment with (+)-usnic acid significantly decreased the invasion of tachyzoite to cardiofibroblasts in vitro; (+)-usnic acid and (+)-usnic acid-liposome extensively prolonged the survival time of mice about 90.9% and 117%, respectively; and improved the ultrastructural changes of tachyzoite, especially in dense granules, rhoptries, endoplasmic reticulum, mitochondria and other membrane organelles. In summary, these results demonstrate that (+)-usnic acid and (+)-usnic acid-liposome with low toxicity have an inhibitory effect on the viability of toxoplasma tachyzoite, and mainly destructed membrane organelles which are connected with the virulence of toxoplasma. These findings provide the basis for further study and development of usnic acid as a potential agent for treating toxoplasmosis. PMID- 27004469 TI - Recurrence of dyskinesia as a side-effect of mirabegron in a patient with Parkinson's disease on DBS (GPi). PMID- 27004470 TI - The influence of light, substrate and seed origin on the germination and establishment of an ant-garden bromeliad. AB - Plant germination and development depend upon a seed's successful dispersal into a suitable habitat and its ability to grow and survive within the surrounding biotic and abiotic environment. The seeds of Aechmea mertensii, a tank-bromeliad species, are dispersed by either Camponotus femoratus or Neoponera goeldii, two ant species that initiate ant gardens (AGs). These two mutualistic ant species influence the vegetative and reproductive traits of the bromeliad through their divergent ecological preferences (i.e. light and substrate). We hypothesised that the seeds dispersed by these two ant species have underlying genetic differences affecting germination, growth and survival of A. mertensii seedlings in different ways. To test this, we used an experimental approach consisting of sowing seeds of A. mertensii: (i) taken from the two AG-ant associations (i.e. seed origin), (ii) in two contrasting light conditions, and (iii) on three different substrates. Light and substrate had significant effects on germination, survival and on eight key leaf traits reflecting plant performance. Seed origin had a significant effect only on germination and on two leaf traits (total dry mass and relative growth rate). Overall, this bromeliad performs better (i.e. high growth and survival rates) when growing both in the shade and in the carton nest developed by C. femoratus ants. These results suggest that the plasticity of the tank bromeliad A. mertensii is mainly due to environment but also to genetic differences related to seed origin, as some traits are heritable. Thus, these two ant species may play contrasting roles in shaping plant evolution and speciation. PMID- 27004473 TI - A Big Heart! Or Not? PMID- 27004472 TI - Soluble Human Leukocyte Antigen-G in the Bronchoalveolar Lavage of Lung Cancer Patients. AB - BACKGROUND: The main function of the HLA-G molecule in its membrane-bound and soluble forms is to inhibit the immune response by acting on CD4+ T cells, cytotoxic T cells, NK cells and dendritic cells. Lung cancer is a leading cause of death worldwide, and annual incidence is high in both women and men. Some studies have reported an increase of HLA-G serum levels in lung cancer, probably generated by tumor cells escaping the antitumor immune response. In this study the concentration of soluble HLA-G in bronchoalveolar lavage (BAL) in patients with primary and metastatic lung cancer was measured to determine its relation with tumor histological type and overall patient status according to the Karnofsky scale. METHODS: Thirty-one lung cancer patients were included. A tumor biopsy was obtained by bronchoscopy and the tumor type was determined by hematoxylin and eosin staining. BAL samples were obtained to measure soluble HLA G concentrations in an ELISA sandwich assay. RESULTS: The average value of soluble HLA-G was 49.04ng/mL. No correlation between soluble HLA-G levels and age, gender or smoking was observed. A highly significant difference was observed in the levels of soluble HLA-G in BAL from patients with different histological types of lung cancer, especially in metastatic tumors. The Karnofsky index showed a significant and inverse correlation with soluble HLA-G levels in BAL. CONCLUSIONS: Soluble HLA-G protein is significantly associated with metastatic tumors and patients with lower Karnofsky index and may be useful as a prognostic marker in lung cancer. PMID- 27004471 TI - Subtle in-scanner motion biases automated measurement of brain anatomy from in vivo MRI. AB - While the potential for small amounts of motion in functional magnetic resonance imaging (fMRI) scans to bias the results of functional neuroimaging studies is well appreciated, the impact of in-scanner motion on morphological analysis of structural MRI is relatively under-studied. Even among "good quality" structural scans, there may be systematic effects of motion on measures of brain morphometry. In the present study, the subjects' tendency to move during fMRI scans, acquired in the same scanning sessions as their structural scans, yielded a reliable, continuous estimate of in-scanner motion. Using this approach within a sample of 127 children, adolescents, and young adults, significant relationships were found between this measure and estimates of cortical gray matter volume and mean curvature, as well as trend-level relationships with cortical thickness. Specifically, cortical volume and thickness decreased with greater motion, and mean curvature increased. These effects of subtle motion were anatomically heterogeneous, were present across different automated imaging pipelines, showed convergent validity with effects of frank motion assessed in a separate sample of 274 scans, and could be demonstrated in both pediatric and adult populations. Thus, using different motion assays in two large non overlapping sets of structural MRI scans, convergent evidence showed that in scanner motion-even at levels which do not manifest in visible motion artifact can lead to systematic and regionally specific biases in anatomical estimation. These findings have special relevance to structural neuroimaging in developmental and clinical datasets, and inform ongoing efforts to optimize neuroanatomical analysis of existing and future structural MRI datasets in non-sedated humans. Hum Brain Mapp 37:2385-2397, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004474 TI - A randomised trial of a computer-delivered screening and brief intervention for postpartum alcohol use. AB - INTRODUCTION AND AIMS: Most women cut down or quit alcohol use during pregnancy, but return to pre-pregnancy levels of use after giving birth. Universal screening and brief intervention for alcohol use has shown promise, but has proven challenging to implement and has rarely been evaluated with postpartum women. This trial evaluated a single 20-min, electronic screening and brief intervention (e-SBI) for alcohol use among postpartum women. DESIGN AND METHODS: In this parallel group randomised trial, 123 postpartum, low-income, primarily African American women meeting criteria for unhealthy alcohol use were randomly assigned to either a tailored e-SBI (n = 61) or a time-matched control condition (n = 62), with follow-up at 3 and 6 months. Hypotheses predicted that 7-day point prevalence abstinence and drinking days would favour the e-SBI condition. RESULTS: No group differences were significant. Blinded follow-up evaluation revealed 7-day point prevalence of 75% for the e-SBI condition versus 82% for control at 3 months (odds ratio = 1.6) and 72% versus 73%, respectively, at 6 months. Drinking days in the past 90 and mean number of drinks per week also showed no significant differences. DISCUSSION AND CONCLUSIONS: This pilot trial failed to support a single-session e-SBI for alcohol use among postpartum women, although findings at the 3-month time point suggested that greater power might confirm transient effects of the e-SBI. As efficacy is likely to vary with e-SBI content and approach, future research should leverage technology's reproducibility and modularity to isolate key components. [Ondersma SJ, Svikis DS, Thacker LR, Beatty JR, Lockhart N. A randomised trial of a computer-delivered screening and brief intervention for postpartum alcohol use. Drug Alcohol Rev 2016;35:710-718]. PMID- 27004477 TI - Purpuric and petechial rashes in adults and children: initial assessment. PMID- 27004476 TI - Optimising health and safety of people who inject drugs during transition from acute to outpatient care: narrative review with clinical checklist. AB - The opioid epidemic in the USA continues to worsen. Medical providers are faced with the challenge of addressing complications from opioid use disorders and associated injection drug use. Unsafe injection practices among people who inject drugs (PWID) can lead to several complications requiring acute care encounters in the emergency department and inpatient hospital. Our objective is to provide a narrative review to help medical providers recognise and address key health issues in PWID, who are being released from the emergency department and inpatient hospital. In the midst of rises in overdose deaths and infections such as hepatitis C, we highlight several health issues for PWID, including overdose and infection prevention. We provide a clinical checklist of actions to help guide providers in the care of these complex patients. The clinical checklist includes strategies also applicable to low-resource settings, which may lack addiction treatment options. Our review and clinical checklist highlight key aspects of optimising the health and safety of PWID. PMID- 27004475 TI - Rif1 and Exo1 regulate the genomic instability following telomere losses. AB - Telomere attrition is linked to cancer, diabetes, cardiovascular disease and aging. This is because telomere losses trigger further genomic modifications, culminating with loss of cell function and malignant transformation. However, factors regulating the transition from cells with short telomeres, to cells with profoundly altered genomes, are little understood. Here, we use budding yeast engineered to lack telomerase and other forms of telomere maintenance, to screen for such factors. We show that initially, different DNA damage checkpoint proteins act together with Exo1 and Mre11 nucleases, to inhibit proliferation of cells undergoing telomere attrition. However, this situation changes when survivors lacking telomeres emerge. Intriguingly, checkpoint pathways become tolerant to loss of telomeres in survivors, yet still alert to new DNA damage. We show that Rif1 is responsible for the checkpoint tolerance and proliferation of these survivors, and that is also important for proliferation of cells with a broken chromosome. In contrast, Exo1 drives extensive genomic modifications in survivors. Thus, the conserved proteins Rif1 and Exo1 are critical for survival and evolution of cells with lost telomeres. PMID- 27004478 TI - Ribosomal P3 protein AtP3B of Arabidopsis acts as both protein and RNA chaperone to increase tolerance of heat and cold stresses. AB - The P3 proteins are plant-specific ribosomal P-proteins; however, their molecular functions have not been characterized. In a screen for components of heat-stable high-molecular weight (HMW) complexes, we isolated the P3 protein AtP3B from heat treated Arabidopsis suspension cultures. By size-exclusion chromatography (SEC), SDS-PAGE and native PAGE followed by immunoblotting with anti-AtP3B antibody, we showed that AtP3B was stably retained in HMW complexes following heat shock. The level of AtP3B mRNA increased in response to both high- and low-temperature stresses. Bacterially expressed recombinant AtP3B protein exhibited both protein and RNA chaperone activities. Knockdown of AtP3B by RNAi made plants sensitive to both high- and low-temperature stresses, whereas overexpression of AtP3B increased tolerance of both conditions. Together, our results suggest that AtP3B protects cells against both high- and low-temperature stresses. These findings provide novel insight into the molecular functions and in vivo roles of acidic ribosomal P-proteins, thereby expanding our knowledge of the protein production machinery. PMID- 27004479 TI - COPD control: Can a consensus be found? AB - There are currently no reliable instruments for assessing the onset and progression of chronic obstructive pulmonary disease (COPD) or predicting its prognosis. Currently, a comprehensive assessment of COPD including several objective and subjective parameters is recommended. However, the lack of biomarkers precludes a correct assessment of COPD severity, which consequently hampers adequate therapeutic approaches and COPD control. In the absence of a definition of "well-controlled disease", a consensus regarding COPD control will be difficult to reach. However, COPD patient assessment should be multidimensional, and anchored in five points: control of symptoms, decline of pulmonary function, levels of physical activity, exacerbations, and Quality of Life. Several non-pharmacological and pharmacological measures are currently available to achieve disease control. Smoking cessation, vaccination, exercise training programs and pulmonary rehabilitation are recognized as important non pharmacological measures but bronchodilators are the pivotal therapy in the control of COPD. This paper discusses several objective and subjective parameters that may bridge the gap between disease assessment and disease control. The authors conclude that, at present, it is not possible to reach a consensus regarding COPD control, essentially due to the lack of objective instruments to measure it. Some recommendations are set forth, but true COPD control awaits further objective assessments. PMID- 27004480 TI - A Changing Landscape for Vitamin A Programs: Implications for Optimal Intervention Packages, Program Monitoring, and Safety. AB - BACKGROUND: Vitamin A deficiency (VAD) remains a widespread public health problem in the developing world, despite changes in under-5 mortality rates, morbidity patterns, and intervention options. OBJECTIVE: This article considers the implications of a changing epidemiologic and programmatic landscape for vitamin A (VA) programs. METHODS: We review progress to prevent VAD and its health consequences, assess gaps in VA status and intervention coverage data, and assess data needed to guide decisions regarding the optimal mix, targeting, and dose of VA interventions to maximize benefit and minimize risk. RESULTS: Vitamin A supplementation programs have contributed to the reduction in under-5 mortality rates, but alone, do not address the underlying problem of inadequate dietary VA intakes and VAD among preschool-aged children in the developing world. A combination of VA interventions (eg, supplementation, fortified foods, multiple micronutrient powders, and lipid-based nutrient supplements) will be required to achieve VA adequacy in most settings. Current efforts to measure the coverage of multiple VA interventions, as well as whether and how much VA children are receiving, are few and fragmented. CONCLUSIONS: Where intervention overlap exists, further effort is needed to monitor VA intakes, ensuring that targeted groups are consuming adequate amounts but not exceeding the tolerable upper intake level. Vitamin A status data will also be critical for navigating the changing landscape of VA programs. Data from these monitoring efforts will help to guide decisions on the optimal mix, targeting, and exposure to VA interventions to maximize public health benefit while minimizing any potential risk. PMID- 27004481 TI - Identification and Characterization of Lipopeptides from Bacillus subtilis B1 Against Sapstain Fungus of Rubberwood Through MALDI-TOF-MS and RT-PCR. AB - Bacillus subtilis is a potent biocontrol agent producing a wide array of antifungal lipopeptides for the inhibition of fungal growth. B. subtilis B1 isolated from market-available compost provided an efficient control of rubberwood sapstain fungus, Lasiodiplodia theobromae. The current study is aimed to identify and characterize the lipopeptides responsible for the biocontrol of rubberwood sapstain fungus by Bacillus subtilis B1. The bacterial whole-cell surface extract from the dual culture of B. subtilis B1 and sapstain fungus (L. theobromae) was analysed using MALDI-TOF-MS. The protonated as well as sodium, potassium adducts of homologues of iturin C, surfactin, bacillomycin D and fengycin A and B were identified and expression of the lipopeptide biosynthetic genes could be confirmed through RT-PCR. This is the first report of mycobacillin and trimethylsilyl derivative of bacilysin during antagonism through MALDI-TOF MS. MALDI-TOF-MS with RT-PCR offered easy platforms to characterize the antifungal lipopeptides. The identification of antifungal lipopeptides can lead to the formulation of prospective biocontrol by-products which have wide-scale utility. PMID- 27004482 TI - Diffuse idiopathic skeletal hyperostosis: Diagnostic, clinical, and paleopathological considerations. AB - Diffuse idiopathic skeletal hyperostosis (DISH) is a disease primarily affecting the spine. However, it is also associated with the ossification/calcification of tendon, ligament, and capsule insertions (entheses) occurring at multiple peripheral sites. The etiology of the condition is unknown, as the name suggests (diffuse idiopathic skeletal hyperostosis), although some correlations with diabetes mellitus, obesity, and age have been noted. Clinical diagnostic criteria have been adapted for paleopathological assessment of archeological skeletal remains, revealing some interesting patterns between monastic and lay populations; showing a higher incidence of DISH among individuals buried in monastic cemeteries. Although fascinating, the mechanisms behind this difference in prevalence are still not fully understood and have been attributed to the relatively richer diets of the monks and priests. The development of diagnostic criteria, where early stage cases of DISH can be identified as well as a better understanding of its causes, is paramount to the prevention of this potentially debilitating condition and perhaps this is where paleopathologists can assist. The use of dry bone rather than living patients for detailed assessment means that paleopathologists are less restricted by the techniques they can use in their investigations and the condition's occurrence in various archeological assemblages can provide interesting insights into its etiology. Clin. Anat. 29:870-877, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004483 TI - Stabilisation of a cranial cervical vertebral fracture using a 3D-printed patient specific drill guide. PMID- 27004484 TI - Minho Affective Sentences (MAS): Probing the roles of sex, mood, and empathy in affective ratings of verbal stimuli. AB - During social communication, words and sentences play a critical role in the expression of emotional meaning. The Minho Affective Sentences (MAS) were developed to respond to the lack of a standardized sentence battery with normative affective ratings: 192 neutral, positive, and negative declarative sentences were strictly controlled for psycholinguistic variables such as numbers of words and letters and per-million word frequency. The sentences were designed to represent examples of each of the five basic emotions (anger, sadness, disgust, fear, and happiness) and of neutral situations. These sentences were presented to 536 participants who rated the stimuli using both dimensional and categorical measures of emotions. Sex differences were also explored. Additionally, we probed how personality, empathy, and mood from a subset of 40 participants modulated the affective ratings. Our results confirmed that the MAS affective norms are valid measures to guide the selection of stimuli for experimental studies of emotion. The combination of dimensional and categorical ratings provided a more fine-grained characterization of the affective properties of the sentences. Moreover, the affective ratings of positive and negative sentences were not only modulated by participants' sex, but also by individual differences in empathy and mood state. Together, our results indicate that, in their quest to reveal the neurofunctional underpinnings of verbal emotional processing, researchers should consider not only the role of sex, but also of interindividual differences in empathy and mood states, in responses to the emotional meaning of sentences. PMID- 27004485 TI - Evaluation of tablet computers for visual function assessment. AB - Recent advances in technology and the increased use of tablet computers for mobile health applications such as vision testing necessitate an understanding of the behavior of the displays of such devices, to facilitate the reproduction of existing or the development of new vision assessment tests. The purpose of this study was to investigate the physical characteristics of one model of tablet computer (iPad mini Retina display) with regard to display consistency across a set of devices (15) and their potential application as clinical vision assessment tools. Once the tablet computer was switched on, it required about 13 min to reach luminance stability, while chromaticity remained constant. The luminance output of the device remained stable until a battery level of 5%. Luminance varied from center to peripheral locations of the display and with viewing angle, whereas the chromaticity did not vary. A minimal (1%) variation in luminance was observed due to temperature, and once again chromaticity remained constant. Also, these devices showed good temporal stability of luminance and chromaticity. All 15 tablet computers showed gamma functions approximating the standard gamma (2.20) and showed similar color gamut sizes, except for the blue primary, which displayed minimal variations. The physical characteristics across the 15 devices were similar and are known, thereby facilitating the use of this model of tablet computer as visual stimulus displays. PMID- 27004486 TI - Can Lextale-Esp discriminate between groups of highly proficient Catalan-Spanish bilinguals with different language dominances? AB - Researchers have recently introduced various LexTALE-type word recognition tests in order to assess vocabulary size in a second language (L2) mastered by participants. These tests correlate well with other measures of language proficiency in unbalanced bilinguals whose second language ability is well below the level of their native language. In the present study, we investigated whether LexTALE-type tests also discriminate at the high end of the proficiency range. In several regions of Spain, people speak both the regional language (e.g., Catalan or Basque) and Spanish to very high degrees. Still, because of their living circumstances, some consider themselves as either Spanish-dominant or regional language dominant. We showed that these two groups perform differently on the recently published Spanish Lextale-Esp: The Spanish-dominant group had significantly higher scores than the Catalan-dominant group. We also showed that the noncognate words of the test have the highest discrimination power. This indicates that the existing Lextale-Esp can be used to estimate proficiency differences in highly proficient bilinguals with Spanish as an L2, and that a more sensitive test could be built by replacing the cognates. PMID- 27004487 TI - Impaired cue identification and intention retrieval underlie prospective memory deficits in patients with first-episode schizophrenia. AB - OBJECTIVE: Schizophrenia is associated with impairment in prospective memory, the ability to remember to carry out an intended action in the future. It has been established that cue identification (detection of the cue event signaling that an intended action should be performed) and intention retrieval (retrieval of an intention from long-term memory following the recognition of a prospective cue) are two important processes underlying prospective memory. The purpose of this study was to examine prospective memory deficit and underlying cognitive processes in patients with first-episode schizophrenia. METHODS: This study examined cue identification and intention retrieval components of event-based prospective memory using a dual-task paradigm in 30 patients with first-episode schizophrenia and 30 healthy controls. All participants were also administered a set of tests assessing working memory and retrospective memory. RESULTS: Both cue identification and intention retrieval were impaired in patients with first episode schizophrenia compared with healthy controls ( ps < 0.05), with a large effect size for cue identification (Cohen's d = 0.98) and a medium effect size for intention retrieval (Cohen's d = 0.62). After controlling for working memory and retrospective memory, the difference in cue identification between patients and healthy controls remained significant. However, the difference in intention retrieval between the two groups was no longer significant. In addition, there was a significant inverse relationship between cue identification and negative symptoms ( r = -0.446, p = 0.013) in the patient group. CONCLUSION: These findings suggest that both cue identification and intention retrieval in event based prospective memory are impaired in patients with first-episode schizophrenia. Cue identification and intention retrieval could be potentially used as biomarkers for early detection and treatment prognosis of schizophrenia. In addition, addressing cue identification deficit through cognitive enhancement training may potentially improve negative symptoms as well. PMID- 27004488 TI - Effects of Helicobacter pylori Infection on the Expressions and Functional Activities of Human Duodenal Mucosal Bicarbonate Transport Proteins. AB - BACKGROUND: The mechanisms for Helicobacter pylori (H. pylori)-induced duodenal ulcerogenesis are not fully understood. In this study, we investigated the effects of H. pylori infection on the expressions and functional activities of human duodenal mucosal bicarbonate transport proteins and hope to further clarify the pathogenesis of H. pylori-associated duodenal ulcer. MATERIALS AND METHODS: The experiments were performed in the patients with H. pylori-associated duodenal ulcers, H. pylori-associated chronic gastritis, and H. pylori-negative healthy subjects. Duodenal mucosal bicarbonate secretion was measured by Ussing Chamber technology. RESULTS: The expressions of duodenal mucosal bicarbonate transport proteins, CFTR (cystic fibrosis transmembrane conductance regulator) and SLC26A6 (solute-linked carrier 26 gene A6), in the patients with H. pylori-associated duodenal ulcers were markedly lower than those in healthy controls. Basal and both forskolin- and prostaglandin E2 -stimulated duodenal mucosal bicarbonate secretions in the patients with H. pylori-associated duodenal ulcers were also lower than those in healthy controls. After anti-H. pylori treatment for H. pylori-associated duodenal ulcers, duodenal mucosal bicarbonate secretion and CFTR and SLC26A6 expressions in H. pylori-eradicated patients recovered to levels comparable to healthy controls, but those were found to be not significantly altered in non-H. pylori-eradicated patients. The further results showed that decreases in the H. pylori-induced CFTR and SLC26A6 expression were related to the severity and virulent factors of H. pylori infection. CONCLUSION: H. pylori infection impairs the expressions and functional activities of duodenal mucosal bicarbonate transport proteins, CFTR and SLC26A6, which contributes to the development of duodenal ulcer. PMID- 27004489 TI - Determinants of patient satisfaction: a systematic review. AB - AIM: A large number of studies have addressed the detection of patient satisfaction determinants, and the results are still inconclusive. Furthermore, it is known that contradicting evidence exists across patient satisfaction studies. This article is the second part of a two-part series of research with a goal to review a current conceptual framework of patient satisfaction for further operationalisation procedures. The aim of this work was to systematically identify and review evidence regarding determinants of patient satisfaction between 1980 and 2014, and to seek the reasons for contradicting results in relationships between determinants and patient satisfaction in the literature to design a further robust measurement system for patient satisfaction. METHOD: This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The search was conducted in PubMed, CINAHL, and Scopus in October 2014. Studies published in full in peer reviewed journals between January 1980 and August 2014 and in the English language were included. We included 109 articles for the synthesis. RESULTS: We found several number of determinants of patient satisfaction investigated in a wide diversity of studies. However, study results were varied due to no globally accepted formulation of patient satisfaction and measurement system. CONCLUSIONS: Health care service quality indicators were the most influential determinants of patient satisfaction across the studies. Among them, health providers' interpersonal care quality was the essential determinant of patient satisfaction. Sociodemographic characteristics were the most varied in the review. The strength and directions of associations with patient satisfaction were found inconsistent. Therefore, person-related characteristics should be considered to be the potential determinants and confounders simultaneously. The selected studies were not able to show all potential characteristics which may have had effects on satisfaction. There is a need for more studies on how cultural, behavioural, and socio-demographic differences affect patient satisfaction, using a standardised questionnaire. PMID- 27004490 TI - Practices and risks associated with operation of tie-down lashings in the vehicle transport industry. AB - Load restraint systems in automobile transport utilise tie-down lashings placed over the car's tyres, which are tensioned manually by the operator using a ratchet assembly. This process has been identified as a significant manual handling injury risk. The aim of this study was to gain insight on the current practices associated with tie-down lashings operation, and identify the gaps between current and optimal practice. We approached this with qualitative and quantitative assessments and one numerical simulation to establish: (i) insight into the factors involved in ratcheting; (ii) the required tension to hold the car on the trailer; and (iii) the tension achieved by drivers in practice and associated joint loads. We identified that the method recommended to the drivers was not used in practice. Drivers instead tensioned the straps to the maximum of their capability, leading to over-tensioning and mechanical overload at the shoulder and elbow. We identified the postures and strategies that resulted in the lowest loads on the upper body during ratcheting (using both hands and performing the task with their full body). This research marks the first step towards the development of a training programme aiming at changing practice to reduce injury risks associated with the operation of tie-down lashings in the automobile transport industry. Practitioner Summary: The study investigated current practice associated with the operation of tie-down lashings through qualitative (interviews) and quantitative (biomechanical analysis) methods. Operators tended to systematically over-tension the lashings and consequently overexert, increasing injury risks. PMID- 27004491 TI - Low serum levels of vitamin B12 in older adults with normal nutritional status by mini nutritional assessment. AB - Undernutrition as well as low levels of vitamin B12 and folic acid are common problems among older adults. However, recommended routine nutritional status assessment tools may result in inadequate vitamin serum levels to go unnoticed. Therefore, the aim of this study is to evaluate the inadequacy of serum levels of vitamin B12 and folic acid within Mini Nutritional Assessment (MNA) classification categories among older adults. A cross-sectional study was conducted with 97 older adults residing in care homes in Portugal. Undernutrition was identified through the MNA, and serum levels of vitamin B12 and folic acid were measured using chemiluminescence. Cognitive function, depressive symptoms and functional characteristics were also assessed using the Abbreviated Mental Test Score, the Epidemiologic Studies Depression Scale and the Barthel Index, respectively. The mean age of older adults was 82.2 (6.3) years; 3.1% were undernourished and 26.8% were at undernutrition risk. In the MNA normal nutritional status group, 11.8% presented vitamin B12 deficiency (<200 pg/ml), 32.4% had low serum levels (200-400 pg/ml) and 4.4% had folic acid deficiency (<3 ng/ml). A high proportion of older adults with low serum levels of vitamin B12 presenting normal nutritional status by MNA was identified. This finding emphasizes the need to evaluate serum vitamin B12 levels, independently of the MNA results. PMID- 27004492 TI - Antenatal breastfeeding intention, confidence and comfort in obese and non-obese primiparous Australian women: associations with breastfeeding duration. AB - BACKGROUND/OBJECTIVES: Maternal adiposity is known to affect breastfeeding initiation and duration via both antenatal and postnatal factors. This study investigates associations between maternal pregravid body mass index (BMI), breastfeeding duration and antenatal breastfeeding confidence, intention and social comfort among primiparous Australian women. SUBJECTS/METHODS: Women in their first pregnancy (n=462) were recruited by convenience sampling in Queensland, Australia. Participants responded to an antenatal and six postnatal questionnaires during their infants' first year between June 2010 and March 2012. Maternal pregravid BMI was examined against breastfeeding duration, participants' antenatal infant feeding intentions and measures of breastfeeding confidence and social comfort. RESULTS: Breastfeeding initiation in this cohort was 97%, but 46% of mothers had ceased breastfeeding at 52 weeks postpartum. Breastfeeding duration differed significantly (chi(2) (2)=7.21, P=0.007) between normal, overweight and obese women. No differences were found in antenatal intention for feeding type nor intended breastfeeding duration by one-way ANOVA (F(2,178)=1.77, P=0.17). More than half of the pregnant respondents anticipated social discomfort breastfeeding in public, with obese women significantly more likely to anticipate discomfort breastfeeding in the presence of close female friends, (chi(2) (1)=5.53, P=0.019). CONCLUSIONS: This study confirmed the risk of premature cessation of breastfeeding for obese mothers. Interventions during pregnancy that address body image issues in relation to breastfeeding may facilitate breastfeeding success for obese mothers and their infants and accrue short- and long-term health benefits for both. PMID- 27004493 TI - Predictive factors of iron depletion in late preterm infants at the postnatal age of 6 weeks. AB - BACKGROUND/OBJECTIVES: Late preterm infants (born ?32 weeks of gestation) are at risk for developing iron deficiency and iron deficiency anaemia, and this may lead to impaired neurodevelopment. In the Netherlands, there is no guideline for standardised iron supplementation in these infants. Individualised iron supplementation has been suggested (that is, treating those infants with the highest risk), but risk factors for deprived iron stores in this specific group of infants are not well documented. SUBJECTS/METHODS: In this prospective multi centre study, we analysed the iron status at the postnatal age of 6 weeks of 68 infants born between 32 and 35 weeks of gestation in the Netherlands. Serum ferritin (SF) <70 MUg/l in the absence of infection (C-reactive protein <5 mg/l) was defined as iron depletion and whenever in combination with a haemoglobin level <110 mg/dl as iron-depleted anaemia. Medical charts were reviewed to identify risk factors. RESULTS: Iron depletion and iron-depleted anaemia were present in 38.2% and 30.9% of the infants, respectively. Infants with a birth weight <1830 g and a SF <155 MUg/l in the first week of life had a 26.4 times higher risk to develop iron depletion (95% confidence interval 3.1-227.0, P=0.003). Multivariate regression analyses also showed that iron depletion was associated with a higher number of blood draws. CONCLUSIONS: Iron depletion is common in late preterm infants at the age of 6 weeks in a setting without standardised iron supplementation. One should consider early individualised iron supplementation for late preterm infants with a low birth weight (<1830 g), and a low SF in the first week of life (<155 MUg/l), as they have a high risk to develop iron depletion. PMID- 27004494 TI - A Real-World Experience With the Supera Interwoven Nitinol Stent in Femoropopliteal Arteries: Midterm Patency Results and Failure Analysis. AB - PURPOSE: To evaluate the safety and midterm patency of the Supera interwoven nitinol stent in a real-world population and determine deployment and patient related factors that may predispose to loss of patency. METHODS: A retrospective analysis was conducted of 111 consecutive limbs from 97 patients (mean age 75.3 years; 68 men) with severe atherosclerotic disease of the superficial femoral and popliteal arteries that were treated with Supera stents between June 2012 and October 2014. Half the patients had claudication (56%); the remainder had rest pain (19%) and tissue loss (26%). Forty-eight (43%) lesions were chronic total occlusions, and more than half were classified as TransAtlantic Inter-Society Consensus C (22%) or D (30%). RESULTS: All 146 Supera stents (1.32 stents per limb) were deployed successfully, extending over a mean length of 175.5+/-130.5 mm to treat lesions averaging 151.5+/-127.1 mm long. At 30 days, Kaplan-Meier estimated freedom from death, target lesion revascularization, and amputation was 97.3%. Primary patency and freedom from clinically driven target lesion revascularization rates were 87.1% and 95.0% at 6 months, respectively, and 78.9% and 87.6% at 12 months, respectively. Four distinct mechanisms for failure were identified in the 13 limbs in which patency was lost; stent intussusception (n=4), compromised inflow or outflow (n=2), gross oversizing (n=1), and neoplastic thrombophilia (n=1); the cause of 5 occlusions could not be identified. CONCLUSION: In this heterogeneous group that included long and complex atheromatous femoropopliteal lesions, the Supera stent achieved excellent clinical and patency results at 1 year. Further improvement may be achieved through careful patient selection and the avoidance of deployment pitfalls. PMID- 27004495 TI - Comparison of a Sheathless Transradial Access With Looping Technique and Transbrachial Access for Carotid Artery Stenting. AB - PURPOSE: To evaluate the feasibility and safety of sheathless transradial access (TRA) with the looping technique for carotid artery stenting (CAS) compared with the transbrachial approach (TBA). METHODS: Among 99 symptomatic patients with a history of transient ischemic attack (TIA) or stroke, 38 patients (mean age 69+/ 10 years; 28 men) with documented internal carotid artery stenosis were selected for CAS via a sheathless TRA and compared with 61 patients who received CAS via the brachial artery. Routine assessments of radial artery patency using duplex ultrasound and clinical follow-up were performed at 1, 6, and 12 months. RESULTS: The sheathless TRA technique offered 100% procedure success; only 1 patient in the sheathless TRA group and 2 patients in the TBA group experienced TIAs during the procedure. There were no major complications (major stroke or 30 day in hospital death) in either group or radial access site complications. The incidence of radial artery occlusion in the sheathless TRA CAS group was 9% (3/33) at 1 year (5 patients died unrelated to the procedure). CONCLUSION: The sheathless TRA with looping technique may be an alternative to transbrachial access for CAS in patients who have small radial arteries and are unsuitable for the transfemoral approach. PMID- 27004496 TI - Impact of Drug-Eluting Stent Implantation for Femoropopliteal In-Stent Occlusion. AB - PURPOSE: To compare optimal balloon angioplasty with nitinol stenting and drug eluting stent (DES) implantation for femoropopliteal in-stent occlusion (ISO). METHODS: A dual center, retrospective study was performed from January 2004 to December 2014 encompassing 110 ISOs after bare nitinol stenting for a femoropopliteal lesion in 100 patients (mean age 72.7+/-10.1 years; 58 men). These patients underwent optimal balloon angioplasty with implantation of a bare stent (conventional group, n=79) or a DES (n=21). The primary endpoint was recurrent in-stent restenosis (Re-ISR); secondary endpoints were recurrent target lesion revascularization (Re-TLR), reocclusion, and major adverse limb events (MALE). Re-ISR or reocclusion was defined as ISR or occlusion after TLR. Restenosis was defined as a peak systolic velocity ratio >2.4 on a duplex scan or >50% stenosis on angiography. Univariate Cox regression analysis was used to identify any relationships between patient and procedure variables and the occurrence of Re-ISR; the results are presented as the hazard ratio (HR) and the 95% confidence interval (CI). RESULTS: The mean follow-up period was 34.9+/-27.4 months. At 2 years, Kaplan-Meier estimated freedom from Re-ISR rates were 79.3% in the DES group and 20.2% in the conventional group, respectively (p<0.001). The rates of freedom from Re-TLR, reocclusion, and MALE at 2 years were 85.7%, 85.9%, and 85.7% in the DES group and 27.1%, 42.5%, and 25.3% in the conventional group, respectively (p<0.001, p=0.006, and p<0.001, respectively). Univariate analysis showed only postprocedure stenosis (HR 1.04, 95% CI 1.02 to 1.07, p<0.001) as a predictor of Re-ISR. Postprocedure ABI (HR 0.06, 95% CI 0.01 to 0.30, p<0.001) and DES use (HR 0.20, 95% CI 0.07 to 0.44, p<0.001) were associated with a lower likelihood of developing Re-ISR. CONCLUSION: In this small comparative study, DES stent implantation gives more favorable outcomes than conventional treatment for ISO after femoropopliteal stenting. PMID- 27004497 TI - The effect of endoscopic sterilization on reproductive behavior and pair bond maintenance of feral pigeons (Columba livia). AB - OBJECTIVE: Problems related to feral pigeons (Columba livia) in cities mainly result from their large numbers due to uncontrolled population growth. The aim of this study was to evaluate whether endoscopic guided sterilization affects the reproductive behavior of feral pigeons under experimental conditions, with the intention of assessing this technique as a potential method for feral pigeon population control. MATERIALS AND METHODS: Five groups of four pairs of feral pigeons each were studied from 8 weeks before, to 7 weeks after sterilization. Both the male and female of the first pair of each group were sterilized, in the second pair only the female and in the third pair only the male was sterilized. The fourth pair acted as a control. All eggs laid were candled to assess fertility. RESULTS: Surgical sterilization had minimal effects on behavior and therefore seems not to have impact on possible field application for population control. All pairs maintained their pair bonds and continued to defend their nesting sites against other pigeons. Only one female copulated with a foreign fertile male while her primary partner was debilitated due to surgery, but returned to him as soon as he recovered. All eggs laid more than 5 days after male sterilization were infertile, whereas all control pairs had fertile eggs. Only one fertile clutch was produced, 5 days after the male's sterilization. Therefore it is assumed that males remain fertile for a limited period of time. CONCLUSION: Endoscopic sterilization seems to be a promising method for field control of feral pigeon populations and sterilization of the male only seems sufficient. PMID- 27004498 TI - The Power of You. PMID- 27004499 TI - Technology, Data, and Behavior: A Cardiac Perspective. PMID- 27004500 TI - Using Informatics to Improve the Care of Patients Susceptible to Malignant Hyperthermia. AB - Perioperative nurses and nurse leaders should understand how to apply a nursing informatics framework and informatics concepts to strengthen data interpretation, transitions in care, and engagement with patients susceptible to malignant hyperthermia (MH) and their family members. Patient outcomes can be improved when informatics solutions facilitate identifying risks, clinical decision making in a crisis situation, retrieving priority information during transitions of care, and involving patients in planning care. Incorporating informatics solutions into existing quality improvement processes can help evaluate knowledge and preparedness related to managing care for a patient in an MH crisis. Informatics solutions can also help enhance interoperability by evaluating workflow related to transitions in care. Perioperative nurses and nurse leaders should advocate for diligence in submitting reports of MH-suspected events to databases. Improved data collection and data sharing enhance aggregated standardized data sets, which can advance research and increase the quality of evidence available with which to guide practice. PMID- 27004501 TI - A Team Approach to Improving Tissue Management. AB - Tissue implant management can be labor intensive because of multiple storage locations and cumbersome tracking systems. The purpose of this quality improvement (QI) project was to enhance patient safety and nursing satisfaction by upgrading our tissue-management facility and processes. We created a centralized storage room for tissue implants and staffed this room during all shifts. Tissue management was executed using tracking software and transportation devices that supported tissue receipt, storage, disposition, documentation, and reporting. Our project resulted in our full compliance with tissue implant requirements from the US Food and Drug Administration (FDA) and The Joint Commission. We also reduced our documentation error rate from 3% to less than 1%, and decreased the tissue-expiration rate by 1.1%. Tissues are now delivered to ORs, which allows RNs to focus on patient care rather than retrieval of implants. Monitoring of the tissue inventory has improved, resulting in the reduction of tissue wastage. PMID- 27004502 TI - Ventricular Assist Device Implantation: Perioperative Nursing Considerations. AB - Treatment for patients in end-stage heart failure has been revolutionized by the development of the ventricular assist device (VAD), an implantable heart pump used for long-term mechanical circulatory support. These devices are now small, lightweight, and efficient continuous-flow pumps that have replaced the larger, heavier, fill-to-empty predecessors. Management of the VAD case requires interdisciplinary effort across a diverse continuum of care and an understanding of new implantation techniques. This article describes current advances in VAD technology, indications for use, and perioperative nursing considerations related to patients who have undergone VAD implantation. PMID- 27004503 TI - Bar Code-Based Management to Enhance Efficiency of a Sterile Supply Unit in Singapore. AB - Sterile surgical instruments are essential for successful surgical outcomes. The Singapore General Hospital's Theatre Sterile Supplies Unit (TSSU) has faced many challenges, including increasing demand for instruments and the need to maintain instruments of greater complexity. To address these challenges, stakeholders from key departments at Singapore General Hospital formed a multidisciplinary team to transform operations in the TSSU. The team adopted and implemented the TSSU Instrument Management System (TIMS) in three phases over five years. The project included standardizing instrument-naming conventions, implementing electronic integration of instrument tracking in the unit, extending traceability of instruments to the major ORs, initiating integrated web-based instrument ordering, and extending the system management of instruments at ambulatory surgery and specialized OR facilities. The implementation of TIMS has improved inventory, supply, and quality management; reduced instrument repairs; and led to savings through increased productivity and lower expenses. PMID- 27004505 TI - Crisis Management of Unstable Tachycardia in the OR. PMID- 27004504 TI - Evaluating Enhancements to a Perioperative Nurse Liaison Program. AB - The impetus for the perioperative nurse liaison (PNL) program at our cancer center was to reduce anxiety for family members of patients undergoing surgery by improving communication between the family and the perioperative team. The purpose of our quality improvement project was to increase contact with family members during the patient's surgery and to support families and surgeons during the postoperative family consult when findings were unexpected. After implementing process changes, the PNLs evaluated the program using a short survey given to families after the postoperative consult. Families reported a reduction in stress and anxiety when intraoperative updates were received either in person or by telephone. In addition, when the PNL accompanied family members to the postoperative consult, the family felt supported when receiving unexpected findings. Further, family contact with the PNL increased from 77% to 98%, and the number of consults with surgeons that included the PNL rose from an average of 254 to 500 per year. PMID- 27004506 TI - Learning Agility: A Critical Competency. PMID- 27004507 TI - Care of the Surgical Patient With Obstructive Sleep Apnea. PMID- 27004509 TI - Unseen Perils of Urinary Catheters. PMID- 27004510 TI - Department of Veterans Affairs Office of Research and Development's pain portfolio. PMID- 27004511 TI - Variation in secondary metabolite production as well as antioxidant and antibacterial activities of Zingiber zerumbet (L.) at different stages of growth. AB - BACKGROUND: Zingiber zerumbet (L.) is a traditional Malaysian folk remedy that contains several interesting bioactive compounds of pharmaceutical quality. METHODS: Total flavonoids and total phenolics content from the leaf, stem, and rhizome of Z. zerumbet at 3 different growth stages (3, 6, and 9 months) were determined using spectrophotometric methods and individual flavonoid and phenolic compounds were identified using ultra-high performance liquid chromatography method. Chalcone Synthase (CHS) activity was measured using a CHS assay. Antioxidant activities were evaluated by ferric reducing antioxidant potential (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. The antibacterial activity was determined against Gram-positive and Gram-negative bacteria using the disc diffusion method. RESULTS: Highest content of total flavonoid [29.7 mg quercetin equivalents (QE)/g dry material (DM)] and total phenolic (44.8 mg gallic acid equivalents (GAE)/g DM) were detected in the rhizome extracts of 9 month-old plants. As the plant matured from 3 to 9 months, the total flavonoid content (TFC) and total phenolic content (TPC) decreased in the leaf, but increased significantly in the rhizomes. Among the secondary metabolites identified, the most abundant, based on the concentrations, were as follows: flavonoids, catechin > quercetin > rutin > luteolin > myricetin > kaempferol; phenolic acids, gallic acid > ferulic acid > caffeic acid > cinnamic acid. Rhizome extracts from 9-month-old plants demonstrated the highest CHS activity (7.48 nkat/mg protein), followed by the 6-month-old rhizomes (5.79 nkat/mg protein) and 3-month-old leaf (4.76 nkat/mg protein). Nine-month-old rhizomes exhibited the highest DPPH activity (76.42 %), followed by the 6-month-old rhizomes (59.41 %) and 3-month-old leaves (57.82 %), with half maximal inhibitory concentration (IC50) of 55.8, 86.4, and 98.5 MUg/mL, respectively, compared to that of alpha- tocopherol (84.19 %; 44.8 MUg/mL) and butylated hydroxytoluene (BHT) (70.25 %; 58.6 MUg/mL). The highest FRAP activity was observed in 9-month old rhizomes, with IC50 of 62.4 MUg/mL. Minimal Inhibitory Concentration (MIC) of Z. zerumbet extracts against Gram-positive and Gram-negative bacteria ranged from 30 to >100 ug/mL. Among the bacterial strains examined, Staphylococcus aureus was sensitive to the leaf extract of Z. zerumbet, with MIC of 30.0 MUg/mL and other strains were sensitive to the rhizome extracts. CONCLUSIONS: Three- and 9-month old plants are recommended when harvesting the leaf and rhizome of Z. zerumbet, respectively, in order to obtain effective pharmaceutical quality of the desired compounds. PMID- 27004512 TI - Optimization of anti-cancer drugs and a targeting molecule on multifunctional gold nanoparticles. AB - Breast cancer is the most common and deadly cancer among women worldwide. Currently, nanotechnology-based drug delivery systems are useful for cancer treatment; however, strategic planning is critical in order to enhance the anti cancer properties and reduce the side effects of cancer therapy. Here, we designed multifunctional gold nanoparticles (AuNPs) conjugated with two anti cancer drugs, TGF-beta1 antibody and methotrexate, and a cancer-targeting molecule, folic acid. First, optimum size and shape of AuNPs was selected by the highest uptake of AuNPs by MDA-MB-231, a metastatic human breast cancer cell line. It was 100 nm spherical AuNPs (S-AuNPs) that were used for further studies. A fixed amount (900 MUl) of S-AuNP (3.8 * 10(8) particles/ml) was conjugated with folic acid-BSA or methotrexate-BSA. Methotrexate on S-AuNP induced cellular toxicity and the optimum amount of methotrexate-BSA (2.83 mM) was 500 MUl. Uptake of S-AuNPs was enhanced by folate conjugation that binds to folate receptors overexpressed by MDA-MB-231 and the optimum uptake was at 500 MUl of folic acid BSA (2.83 mM). TGF-beta1 antibody on S-AuNP reduced extracellular TGF-beta1 of cancer cells by 30%. Due to their efficacy and tunable properties, we anticipate numerous clinical applications of multifunctional gold nanospheres in treating breast cancer. PMID- 27004513 TI - Comparison of the porcine uterine smooth muscle contractility on days 12-14 of the estrous cycle and pregnancy. AB - BACKGROUND: Uterine contractile activity is very important for many reproductive functions including embryo transport, implantation, gestation and parturition. Abnormal contractility leads to implantation failure, spontaneous miscarriage, preterm birth and many other disorders. The objective of the present study was to assess the effects of acetylcholine (ACh), noradrenaline (NA), oxytocin (OT) and prostaglandins F2alpha (PGF2alpha) and E2 (PGE2) on the contraction of uterine strips collected from the horns of cyclic gilts (12-14 days of the estrous cycle group I) and from pregnant (12-14 days after first insemination gilts in which one of the uterine horn was gravid (group IIa) and the second one was non-gravid (group IIb). Uterine strips consisting of the endometrium with the myometrium and myometrium alone were examined. RESULTS: ACh increased the tension in all groups as compared to the pretreatment period, and the increase was the highest in group IIb; the amplitude decreased in all groups, and the frequency increased mainly in groups I and IIa. NA did not affect the tension in any group, but decreased the amplitude and frequency in group IIb as compared to groups I and IIa. OT caused the highest increase in the tension in group IIb, a decrease in the amplitude and an increase in the frequency of contractions as compared to the pretreatment period. PGF2alpha induced the highest increase in the tension and amplitude in group IIb, with a decline in the frequency in this group. PGE2 increased the tension and frequency only in group IIb, and caused the greatest eduction in the amplitude in this group. CONCLUSIONS: These results indicate that contractility of the porcine smooth muscle collected from uterine horns with embryos was different from those obtained from the uterine horns without embryos and the horns of cyclic gilts. PMID- 27004514 TI - Towards better guidance on caseload thresholds to promote positive tuberculosis treatment outcomes: a cohort study. AB - BACKGROUND: In low-incidence countries, clinical experience of tuberculosis is becoming more limited, with potential consequences for patient outcomes. In 2007, the Department of Health released a guidance 'toolkit' recommending that tuberculosis patients in England should not be solely managed by clinicians who see fewer than 10 cases per year. This caseload threshold was established to try to improve treatment outcomes and reduce transmission, but was not evidence based. We aimed to assess the association between clinician or hospital caseload and treatment outcomes, as well as the relative suitability of making recommendations using each caseload parameter. METHODS: Demographic and clinical data for tuberculosis cases in England notified to Public Health England's Enhanced Tuberculosis Surveillance system between 2003 and 2012 were extracted. Mean clinician and hospital caseload over the past 3 years were calculated and treatment outcomes grouped into good/neutral and unfavourable. Caseloads over time and their relationship with outcomes were described and analysed using random effects logistic regression, adjusted for clustering. RESULTS: In a fully adjusted multivariable model (34,707 cases)there was very strong evidence that management of tuberculosis by clinicians with fewer than 10 cases per year was associated with greater odds of an unfavourable outcome compared to clinicians who managed greater numbers of cases (cluster-specific odds ratio, 1.14; 95 % confidence interval, 1.05-1.25; P = 0.002). The relationship between hospital caseload and treatment outcomes was more complex and modified by a patient's place of birth and ethnicity. The clinician caseload association held after adjustment for hospital caseload and when the clinician caseload threshold was reduced down to one. CONCLUSIONS: Despite the relative ease of making recommendations at the hospital level and the greater reliability of recorded hospital versus named clinician, our results suggest that clinician caseload thresholds are more suitable for clinical guidance. The current recommended clinician caseload threshold is functional. Sensitivity analyses reducing the threshold indicated that clinical experience is pertinent even at very low average caseloads, which is encouraging for low burden settings. PMID- 27004515 TI - CTCF-mediated chromatin loops enclose inducible gene regulatory domains. AB - BACKGROUND: The CCTC-binding factor (CTCF) protein is involved in genome organization, including mediating three-dimensional chromatin interactions. Human patient lymphocytes with mutations in a single copy of the CTCF gene have reduced expression of enhancer-associated genes involved in response to stimuli. We hypothesize that CTCF interactions stabilize enhancer-promoter chromatin interaction domains, facilitating increased expression of genes in response to stimuli. Here we systematically investigate this model using computational analyses. RESULTS: We use CTCF ChIA-PET data from the ENCODE project to show that CTCF-associated chromatin loops have a tendency to enclose regions of enhancer regulated stimulus responsive genes, insulating them from neighboring regions of constitutively expressed housekeeping genes. To facilitate cell type-specific CTCF loop identification, we develop an algorithm to predict CTCF loops from ChIP seq data alone by exploiting the CTCF motif directionality in loop anchors. We apply this algorithm to a hundred ENCODE cell line datasets, confirming the universality of our observations as well as identifying a general distinction between primary and immortal cells in loop-enclosed gene content. Finally, we combine the existing evidence to propose a model for the formation of CTCF loops in which partner sites are brought together by chromatin template reeling through stationary RNA polymerases, consistent with the transcription factory hypothesis. CONCLUSIONS: We provide computational evidence that CTCF-mediated chromatin interactions enclose domains of stimulus responsive enhancer-regulated genes, insulating them from nearby housekeeping genes. PMID- 27004516 TI - Microglial migration and interactions with dendrimer nanoparticles are altered in the presence of neuroinflammation. AB - BACKGROUND: Microglial cells have been implicated in neuroinflammation-mediated injury in the brain, including neurodevelopmental disorders such as cerebral palsy (CP) and autism. Pro-inflammatory activation of microglial cells results in the impairment of their neuroprotective functions, leading to an exaggerated, ongoing immune dysregulation that can persist long after the initial insult. We have previously shown that dendrimer-mediated delivery of an anti-inflammatory agent can attenuate inflammation in a rabbit model of maternal inflammation induced CP and significantly improve the motor phenotype, due to the ability of the dendrimer to selectively localize in activated microglia. METHODS: To elucidate the interactions between dendrimers and microglia, we created an organotypic whole-hemisphere brain slice culture model from newborn rabbits with and without exposure to inflammation in utero. We then used this model to analyze the dynamics of microglial migration and their interactions with dendrimers in the presence of neuroinflammation. RESULTS: Microglial cells in animals with CP had an amoeboid morphology and impaired cell migration, demonstrated by decreased migration distance and velocity when compared to cells in healthy, age-matched controls. However, this decreased migration was associated with a greater, more rapid dendrimer uptake compared to microglial cells from healthy controls. CONCLUSIONS: This study demonstrates that maternal intrauterine inflammation is associated with impaired microglial function and movement in the newborn brain. This microglial impairment may play a role in the development of ongoing brain injury and CP in the offspring. Increased uptake of dendrimers by the "impaired" microglia can be exploited to deliver drugs specifically to these cells and modulate their functions. Host tissue and target cell characteristics are important aspects to be considered in the design and evaluation of targeted dendrimer-based nanotherapeutics for improved and sustained efficacy. This ex vivo model also provides a rapid screening tool for evaluation of the effects of various therapies on microglial function. PMID- 27004518 TI - Fundus autofluorescence and optical coherence tomography of a macular cherry-red spot in a case report of sialidosis. AB - BACKGROUND: Sialidosis is a rare lysosomal storage disorder characterized by deficiency of alpha-N-acetyl neuraminidase. The macular cherry-red spot, which could be important for diagnosis, is a distinctive feature of its ocular manifestation. We evaluated the fundus autofluorescence (FAF) and optical coherence tomography (OCT) images of a juvenile patient who presented with vision decrease and was later confirmed with genetic sialidosis. CASE PRESENTATION: A 13 year-old Chinese male presented with bilateral decreased vision over the past 2 years before his initial visit. Funduscopic examination revealed a macular cherry red bilateral spot. FAF showed hyperreflective areas surrounding a central hyporeflective fovea in both eyes. OCT revealed increased reflectivity in the ganglion cell layer in both maculae without a definite boundary between the hyperreflective and normal areas. These findings suggested that lipofuscin had accumulated in the retinal ganglion cells, which is a distinctive ocular feature in metabolic central nervous system (CNS) disorders. He was later confirmed with genetic sialidosis. CONCLUSIONS: FAF and OCT images are very sensitive and useful techniques for diagnosing lysosomal storage disease of the CNS, and are helpful in evaluating the extent of damage in retinal ganglion cells. PMID- 27004517 TI - The CORE Service Improvement Programme for mental health crisis resolution teams: study protocol for a cluster-randomised controlled trial. AB - BACKGROUND: As an alternative to hospital admission, crisis resolution teams (CRTs) provide intensive home treatment to people experiencing mental health crises. Trial evidence supports the effectiveness of the CRT model, but research suggests that the anticipated reductions in inpatient admissions and increased user satisfaction with acute care have been less than hoped for following the scaling up of CRTs nationally in England, as mandated by the National Health Service (NHS) Plan in 2000. The organisation and service delivery of the CRTs vary substantially. This may reflect the lack of a fully specified CRT model and the resources to enhance team model fidelity and to improve service quality. We will evaluate the impact of a CRT service improvement programme over a 1-year period on the service users' experiences of care, service use, staff well-being, and team model fidelity. METHODS/DESIGN: Twenty-five CRTs from eight NHS Trusts across England will be recruited to this cluster-randomised trial: 15 CRTs will be randomised to receive the service improvement programme over a 1-year period, and ten CRTs will not receive the programme. Data will be collected from 15 service users and all clinical staff from each participating CRT at baseline and at the end of the intervention. Service use data will be collected from the services' electronic records systems for two 6-month periods: the period preceding and the period during months 7-12 of the intervention. The study's primary outcome is service user satisfaction with CRT care, measured using a client satisfaction questionnaire. Secondary outcomes include the following: perceived continuity of care, hospital admission rates and bed use, rates of readmission to acute care following CRT support, staff morale, job satisfaction, and general health. The adherence of the services to a model of best practice will be assessed at baseline and follow-up. Outcomes will be compared between the intervention and control teams, adjusting for baseline differences and participant characteristics using linear random effects modelling. Qualitative investigations with participating CRT managers and staff and programme facilitators will explore the experiences of the service improvement programme. DISCUSSION: Our trial will show whether a theoretically underpinned and clearly defined package of resources are effective in supporting service improvement and improving outcomes for mental health crisis resolution teams. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47185233. PMID- 27004520 TI - Perceptions about the relative importance of patient care-related topics: a single institutional survey of its anesthesiologists, nurse anesthetists, and surgeons. AB - BACKGROUND: Persistently variable success has been experienced in locally translating even well-grounded national clinical practice guidelines, including in the perioperative setting. We have sought greater applicability and acceptance of clinical practice guidelines and protocols with our novel Perioperative Risk Optimization and Management Planning Tool (PROMPTTM). This study was undertaken to survey our institutional perioperative clinicians regarding (a) their qualitative recommendations for (b) their quantitative perceptions of the relative importance of a series of clinical issues and patient medical conditions as potential topics for creating a PROMPTTM. METHODS: We applied a mixed methods research design that involved collecting, analyzing, and "mixing" both qualitative and quantitative methods and data in a single study to answer a research question. Survey One was qualitative in nature and asked the study participants to list as free text up to 12 patient medical conditions or clinical issues that they perceived to be high priority topics for development of a PROMPTTM. Survey Two was quantitative in nature and asked the study participants to rate each of these 57 specific, pre-selected clinical issues and patient medical conditions on an 11-point Likert scale of perceived importance as a potential topic for a PROMPTTM. The two electronic, online surveys were completed by participants who were recruited from the faculty in our Department of Anesthesiology and Perioperative Medicine and Department of Surgery, and the cohort of hospital-employed certified registered nurse anesthetists. RESULTS: A total of 57 possible topics for a PROMPTTM was created and prioritized by our stakeholders. A strong correlation (r = 0.82, 95% CI: 0.71, 0.89, P < 0.001) was observed between the quantitative clinician survey rating scores reported by the anesthesiologists/certified registered nurse anesthetists versus the surgeons. The quantitative survey displayed strong inter-rater reliability (ICC = 0.92, P < 0.001). CONCLUSIONS: Our qualitative clinician stakeholder survey generated a comprehensive roster of clinical issues and patient medical conditions. Our subsequent quantitative clinician stakeholder survey indicated that there is generally strong agreement among anesthesiologists/certified registered nurse anesthetists and surgeons about the relative importance of these clinical issues and patient medical conditions as potential topics for perioperative optimization and risk management. PMID- 27004519 TI - Cefepime shows good efficacy and no antibiotic resistance in pneumonia caused by Serratia marcescens and Proteus mirabilis - an observational study. AB - BACKGROUND: Many antibiotics have no effect on Gram-positive and Gram-negative microbes, which necessitates the prescription of broad-spectrum antimicrobial agents that can lead to increased risk of antibiotic resistance. These pathogens constitute a further threat because they are also resistant to numerous beta lactam antibiotics, as well as other antibiotic groups. This study retrospectively investigates antimicrobial resistance in hospitalized patients suffering from pneumonia triggered by Gram-negative Serratia marcescens or Proteus mirabilis. METHODS: The demographic and clinical data analyzed in this study were obtained from the clinical databank of the HELIOS Clinic, Witten/Herdecke University, Wuppertal, Germany, for inpatients presenting with pneumonia triggered by S. marcescens or P. mirabilis from 2004 to 2014. An antibiogram was conducted for the antibiotics utilized as part of the management of patients with pneumonia triggered by these two pathogens. RESULTS: Pneumonia was caused by Gram-negative bacteria in 115 patients during the study period from January 1, 2004, to August 12, 2014. Of these, 43 (37.4 %) hospitalized patients [26 males (60.5 %, 95 % CI 45.9 %-75.1 %) and 17 females (39.5 %, 95 % CI 24.9 % 54.1 %)] with mean age of 66.2 +/- 13.4 years had pneumonia triggered by S. marcescens, while 20 (17.4 %) patients [14 males (70 %, 95 % CI 49.9 %-90.1 %) and 6 females (30 %, 95 % CI 9.9 %-50.1 %)] with a mean age of 64.6 +/- 12.8 years had pneumonia caused by P. mirabilis. S. marcescens showed an increased antibiotic resistance to ampicillin (100 %), ampicillin-sulbactam (100 %), and cefuroxime (100 %). P. mirabilis had a high resistance to tetracycline (100 %) and ampicillin (55 %). S. marcescens (P < 0.0001) and P. mirabilis (P = 0.0003) demonstrated no resistance to cefepime in these patients with pneumonia. CONCLUSIONS: S. marcescens and P. mirabilis were resistant to several commonly used antimicrobial agents, but showed no resistance to cefepime. PMID- 27004521 TI - Seasonal occurrence and microhabitat specificity of Paradiplozoon ichthyoxanthon Avenant-Oldewage in Avenant-Oldewage et al., 2014 (Monogenea: Diplozoidae) infecting Labeobarbus aeneus (Burchell) (Teleostei: Cyprinidae) from the Vaal Dam, South Africa: water quality and host size as determining factors? PMID- 27004522 TI - Inhibition of peritoneal metastasis of human gastric cancer cells by dextran sulphate through the reduction in HIF-1alpha and ITGbeta1 expression. AB - The aim of the present study was to investigate the effects of dextran sulphate (DS) on HIF-1alpha and integrin beta1 (ITGbeta1) expression in human gastric cancer cells, the correlation between HIF-1alpha and ITGbeta1 expression and the influence of DS on the peritoneal metastasis of human gastric cancer cells. In in vitro experiments, BGC-823 cells in the experimental and control groups were administered DS and PBS, respectively, and exposed to hypoxic conditions for different periods. Immunocytochemistry, western blot and RT-PCR analyses were used to evaluate HIF-1alpha and ITGbeta1 expression levels. In in vivo experiments, an animal model was established by injecting BGC-823 cells into nude mice. The experimental and control groups received DS and PBS injections, respectively. The mice were euthanized at different times, and the number of tumor nodules in the celiac implantation was recorded. Immunohistochemistry, RT PCR and western blot analyses were used to detect HIF-1alpha and ITGbeta1 expression in the tumor nodules of the greater omentum. The in vitro and in vivo results revealed that HIF-1alpha and ITGbeta1 expression levels in the experimental group were significantly lower than those in the control group (P<0.05), and the expression levels of these factors were positively correlated with each other. The number of tumor nodules in the in vivo experiments was notably less in the experimental group than that noted in the control group (P<0.01). In conclusion, DS may act through inhibition of HIF-1alpha expression, which decreased ITGbeta1 expression, consequently reducing tumor metastasis. PMID- 27004523 TI - Advances in pain management for Veterans: Current status of research and future directions. PMID- 27004524 TI - Impact of Room Location on UV-C Irradiance and UV-C Dosage and Antimicrobial Effect Delivered by a Mobile UV-C Light Device. AB - OBJECTIVE To evaluate ultraviolet C (UV-C) irradiance, UV-C dosage, and antimicrobial effect achieved by a mobile continuous UV-C device. DESIGN Prospective observational study. METHODS We used 6 UV light sensors to determine UV-C irradiance (W/cm2) and UV-C dosage (uWsec/cm2) at various distances from and orientations relative to the UV-C device during 5-minute and 15-minute cycles in an ICU room and a surgical ward room. In both rooms, stainless-steel disks inoculated with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus (VRE), and Clostridium difficile spores were placed next to sensors, and UV-C dosages and log10 reductions of target organisms achieved during 5-minute and 15-minute cycles were determined. Mean irradiance and dosage readings were compared using ANOVA. RESULTS Mean UV-C irradiance was nearly 1.0E 03 W/cm2 in direct sight at a distance of 1.3 m (4 ft) from the device but was 1.12E-05 W/cm2 on a horizontal surface in a shaded area 3.3 m (10 ft) from the device (P4 to 1-3 for MRSA, >4 to 1-2 for VRE and >4 to 0 log10 for C. difficile spores, depending on the distance from, and orientation relative to, the device with 5-minute and 15-minute cycles. CONCLUSION UV-C irradiance, dosage, and antimicrobial effect received from a mobile UV-C device varied substantially based on location in a room relative to the UV-C device. Infect Control Hosp Epidemiol 2016;37:667-672. PMID- 27004526 TI - Biocidal effects of stem bark extract of Chrysophyllum albidium G. Don on vancomycin-resistant Staphylococcus aureus. AB - BACKGROUND: Staphylococcus aureus causes variety of infections in humans and animals worldwide and predominates in surgical wound infections. This study assessed the antimicrobial potential of the stem bark extract of Chrysophyllum albidum against an array of vancomycin resistant Staphylococcus aureus (VRSA) isolated from clinical samples. METHODS: The methanolic crude extract of the plant was preliminary screened for the presence of phytochemicals; after then, the extract was partitioned into n-hexane, chloroform, ethyl acetate and butanol fractions. A range of concentrations of the plant extract fractions was prepared to assess its antimicrobial potency; the minimum inhibitory concentrations (MICs); the minimum bactericidal concentrations (MBCs); the rate of killing; the potassium ion leakage potential and nucleotides leakage ability against the VRSAs. RESULTS: The phytochemical screening revealed the presence of tannins, alkaloids, flavonoids, saponins, steroids, reducing sugars and terpenoids as major phytoconstituents resident in the crude plant extract. The two active fractions (n-hexane and butanol) at a concentration of 10 mg/ml exhibited antibacterial activities with the MIC and MBC values for the fractions ranged between 0.63-10 mg/ml and 1.25-10 mg/ml respectively. The time kill assay revealed that the antibacterial action of the two fractions are time and concentration dependent; the n-hexane and butanol fractions achieved 100 % kill on the test isolates at a concentration of 3 * MIC and 2 * MIC respectively after 120 min of reaction time. Varying amount of potassium ions as well as nucleotides were leaked from the test cells by n-hexane and butanol fractions. CONCLUSIONS: This study has established the possibility of developing antimicrobial agents of natural origin to manage possible infection from vancomycin resistant Staphylococcus aureus that are now developing multi-resistance against many antibiotics. PMID- 27004525 TI - Genome-wide analysis of ionotropic receptors provides insight into their evolution in Heliconius butterflies. AB - BACKGROUND: In a world of chemical cues, smell and taste are essential senses for survival. Here we focused on Heliconius, a diverse group of butterflies that exhibit variation in pre- and post-zygotic isolation and chemically-mediated behaviors across their phylogeny. Our study examined the ionotropic receptors, a recently discovered class of receptors that are some of the most ancient chemical receptors. RESULTS: We found more ionotropic receptors in Heliconius (31) than in Bombyx mori (25) or in Danaus plexippus (27). Sixteen genes in Lepidoptera were not present in Diptera. Only IR7d4 was exclusively found in butterflies and two expansions of IR60a were exclusive to Heliconius. A genome-wide comparison between 11 Heliconius species revealed instances of pseudogenization, gene gain, and signatures of positive selection across the phylogeny. IR60a2b and IR60a2d are unique to the H. melpomene, H. cydno, and H. timareta clade, a group where chemosensing is likely involved in pre-zygotic isolation. IR60a2b also displayed copy number variations (CNVs) in distinct populations of H. melpomene and was the only gene significantly higher expressed in legs and mouthparts than in antennae, which suggests a gustatory function. dN/dS analysis suggests more frequent positive selection in some intronless IR genes and in particular in the sara/sapho and melpomene/cydno/timareta clades. IR60a1 was the only gene with an elevated dN/dS along a major phylogenetic branch associated with pupal mating. Only IR93a was differentially expressed between sexes. CONCLUSIONS: All together these data make Heliconius butterflies one of the very few insects outside Drosophila where IRs have been characterized in detail. Our work outlines a dynamic pattern of IR gene evolution throughout the Heliconius radiation which could be the result of selective pressure to find potential mates or host-plants. PMID- 27004527 TI - Killing of Gyrodactylus salaris by heat and chemical disinfection. AB - BACKGROUND: Gyrodactylus salaris is a monogenean, which has collapsed tens of wild Atlantic salmon populations. One of the means of preventing the spread of the parasite is the disinfection of the fishing equipment, which is used in the rivers having susceptible salmon populations. Little is known about the dosage of disinfectants against G. salaris. There are not standards for the testing of disinfectants against multicellular parasites. The present investigation developed a method to test disinfectants and examined the effectiveness of heated water and a commercially available disinfectant (Virkon S) in killing G. salaris. Individual G. salaris worms were followed under the microscope during treatment with heated water or Virkon S disinfectant blend. The logarithm of the time needed to kill the parasite was used as a dependent variable in linear regression. The upper 99.98 % prediction line for the dependent variable was used to obtain a value resembling the time needed for a 4 log reduction of the microbial pathogen, which is commonly used as a criterion for disinfectants. Also 6 log reduction was applied. RESULTS: Exposure to a relatively low temperature was found to kill the parasite. Even 5-50 min treatment (=10-100 times the 99.98 % upper prediction value) with heated water at 40 degrees C might be used. This would enable the utilisation of hot tap water in the disinfection of fishing gear. The present practice of 1 % Virkon S for 15 min was also found to kill the parasite. CONCLUSIONS: The follow-up of single parasites of a test population and the use of the calculated upper predictive line in the regression analysis offers a method to analyse the effects of disinfectants on parasites like G. salaris. The results of our tests give possibilities for using disinfection methods, which may be more acceptable by the fishermen than the present ones. PMID- 27004528 TI - On the effect of walking surface stiffness on inter-limb coordination in human walking: toward bilaterally informed robotic gait rehabilitation. AB - BACKGROUND: Robotic devices have been utilized in gait rehabilitation but have only produced moderate results when compared to conventional physiotherapy. Because bipedal walking requires neural coupling and dynamic interactions between the legs, a fundamental understanding of the sensorimotor mechanisms of inter-leg coordination during walking, which are not well understood but are systematically explored in this study, is needed to inform robotic interventions in gait therapy. METHODS: In this study we investigate mechanisms of inter-leg coordination by utilizing novel sensory perturbations created by real-time control of floor stiffness on a split-belt treadmill. We systematically alter the unilateral magnitude of the walking surface stiffness and the timing of these perturbations within the stance phase of the gait cycle, along with the level of body-weight support, while recording the kinematic and muscular response of the uperturbed leg. This provides new insight into the role of walking surface stiffness in inter-leg coordination during human walking. Both paired and unpaired unadjusted t-tests at the 95 % confidence level are used in the approriate scernario to determine statistical significance of the results. RESULTS: We present results of increased hip, knee, and ankle flexion, as well as increased tibialis anterior and soleus activation, in the unperturbed leg of healthy subjects that is repeatable and scalable with walking surface stiffness. The observed response was not impacted by the level of body-weight support provided, which suggests that walking surface stiffness is a unique stimulus in gait. In addition, we show that the activation of the tibialis anterior and soleus muscles is altered by the timing of the perturbations within the gait cycle. CONCLUSIONS: This paper characterizes the contralateral leg's response to ipsilateral manipulations of the walking surface and establishes the importance of walking surface stiffness in inter-leg coordination during human walking. PMID- 27004530 TI - The HI HOPES data set of deaf children under the age of 6 in South Africa: maternal suspicion, age of identification and newborn hearing screening. AB - BACKGROUND: Identification of deafness before 3 months of age substantially improves the socio-linguistic and cognitive development of deaf children. Existing studies demonstrating the feasibility of newborn hearing screening in South Africa have used small samples unrepresentative of general population characteristics. This study establishes the characteristics of the largest data set of deaf infants and their families in South Africa on which there is baseline and longitudinal data (n = 532); explores its representativeness in terms of socio-demographic features and reports on access to and quality of newborn hearing screening within the sample. It examines specifically the relationship between age of maternal suspicion of childhood deafness and age of identification of deafness by cohort characteristics. METHODS: Secondary analysis, using descriptive and inferential statistics, of a pre-existing longitudinal data set (n = 532) of deaf infants under 6 years of age, and their families, collected as routine monitoring of the HI HOPES (HH) early intervention programme. RESULTS: The HH cohort is representative in terms of racial profile and private/public health care use but displays slightly higher level of maternal education and slightly lower socio-economic status than national comparators. 102 out of 532 infants had undergone newborn hearing screening, resulting in 29 true positives, 15 of whom would have met the criteria for targeted screening. Later onset deafness does not account for the 73 false negatives. The median age of maternal suspicion (n = 247) of infant deafness was 18 months; the median age of identification of 28 months. Age of identification was unrelated to private/public health care status. The median delay between age of suspicion and age of identification was significantly longer in the public sector (7 m; IQR 0 15 m) compared to the private sector (2 m; IQR 0-8.5 m) (p = 0.035). Age of suspicion was unrelated to level of maternal education. Earlier age of suspicion did not predict earlier identification. CONCLUSION: Targeted screening as timely response to maternal suspicion offers a viable means to reduce substantially the age of identification of deafness in South Africa until implementation of newborn hearing screening on a population-wide basis can be justified. PMID- 27004531 TI - Efficacy and safety of carbetocin applied as an intravenous bolus compared to as a short-infusion for caesarean section: study protocol for a randomised controlled trial. AB - BACKGROUND: The two most commonly used uterotonic drugs in caesarean section are oxytocin and carbetocin, a synthetic oxytocin analogue. Carbetocin has a longer half-life when compared to oxytocin, resulting in a reduced use of additional uterotonics. Oxytocin is known to cause fewer cardiovascular side effects when administered as a short-infusion compared to as an intravenous bolus. Based on these findings, we aim at comparing carbetocin 100 mcg given as a slow intravenous bolus with carbetocin 100 mcg applied as a short-infusion in 100 ml 0.9 % sodium chloride in women undergoing a planned or unplanned caesarean delivery. We hypothesise uterine contraction not to be inferior to a bolus application (primary efficacy endpoint) and greater haemodynamic stability to be achieved after a short-infusion than after a bolus administration, as measured by heart rate and mean arterial blood pressure (primary safety endpoint). METHODS/DESIGN: This is a prospective, double-blind, randomised controlled, investigator-initiated, non-inferiority trial taking place at the University Hospital Basel, Switzerland. Uterine tone is quantified by manual palpation by the obstetrician using a linear analogue scale from 0 to 100 at 2, 3, 5 and 10 minutes after cord clamping. We will evaluate whether the lower limit of the confidence interval for the difference of the maximal uterine tone within the first 5 minutes after cord clamping between both groups does not include the pre specified non-inferiority limit of -10. Both haemodynamic secondary endpoints will be analysed using a linear regression model, adjusting for the baseline value and the dosage of vasoactive drug given between cord clamping and 1 minute thereafter, in order to investigate superiority of a short-infusion as compared to a bolus application. We will follow the extension of CONSORT guidelines for reporting the results of non-inferiority trials. DISCUSSION: Haemodynamic stability and adequate uterine tone are important outcomes in caesarean sections. The results of this trial may be used to optimise these factors and thereby increase patient safety due to a reduction in cardiovascular side effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT02221531 on 19 August 2014 and www.kofam.ch SNCTP000001197 on 15 November 2014. PMID- 27004533 TI - A new mite species Schizocoptes daberti sp. n. (Acariformes: Chirodiscidae) from Chrysochloris stuhlmanni Matsche (Afrosoricida: Chrysochloridae) in the Democratic Republic of the Congo. PMID- 27004529 TI - Tuberculosis incidence is high in HIV-infected African children but is reduced by co-trimoxazole and time on antiretroviral therapy. AB - BACKGROUND: There are few data on tuberculosis (TB) incidence in HIV-infected children on antiretroviral therapy (ART). Observational studies suggest co trimoxazole prophylaxis may prevent TB, but there are no randomized data supporting this. The ARROW trial, which enrolled HIV-infected children initiating ART in Uganda and Zimbabwe and included randomized cessation of co-trimoxazole prophylaxis, provided an opportunity to estimate the incidence of TB over time, to explore potential risk factors for TB, and to evaluate the effect of stopping co-trimoxazole prophylaxis. METHODS: Of 1,206 children enrolled in ARROW, there were 969 children with no previous TB history. After 96 weeks on ART, children older than 3 years were randomized to stop or continue co-trimoxazole prophylaxis; 622 were eligible and included in the co-trimoxazole analysis. Endpoints, including TB, were adjudicated blind to randomization by an independent endpoint review committee (ERC). Crude incidence rates of TB were estimated and potential risk factors, including age, sex, center, CD4, weight, height, and initial ART strategy, were explored in multivariable Cox proportional hazards models. RESULTS: After a median of 4 years follow-up (3,632 child-years), 69 children had an ERC-confirmed TB diagnosis. The overall TB incidence was 1.9/100 child-years (95% CI, 1.5-2.4), and was highest in the first 12 weeks following ART initiation (8.8/100 child-years (5.2-13.4) versus 1.2/100 child years (0.8-1.6) after 52 weeks). A higher TB risk was independently associated with younger age (<3 years), female sex, lower pre-ART weight-for-age Z-score, and current CD4 percent; fewer TB diagnoses were observed in children on maintenance triple nucleoside reverse transcriptase inhibitor (NRTI) ART compared to standard non-NRTI + 2NRTI. Over the median 2 years of follow-up, there were 20 ERC-adjudicated TB cases among 622 children in the co-trimoxazole analysis: 5 in the continue arm and 15 in the stop arm (hazard ratio (stop: continue) = 3.0 (95% CI, 1.1-8.3), P = 0.028). TB risk was also independently associated with lower current CD4 percent (P <0.001). CONCLUSIONS: TB incidence varies over time following ART initiation, and is particularly high during the first 3 months post ART, reinforcing the importance of TB screening prior to starting ART and use of isoniazid preventive therapy once active TB is excluded. HIV-infected children continuing co-trimoxazole prophylaxis after 96 weeks of ART were diagnosed with TB less frequently, highlighting a potentially important role of co-trimoxazole in preventing TB. PMID- 27004532 TI - Part 2 - Coronary angiography with gadofosveset trisodium: a prospective intra subject comparison for dose optimization for 100 % efficiency imaging. AB - BACKGROUND: Three tesla (3T) coronary magnetic resonance angiography (MRA) may be optimized using gadolinium-based contrast agents (GBCA) such as gadofosveset trisodium. The goal of this study was to evaluate if there is a qualitative or quantitative improvement in the coronary arteries with variation in contrast dose. METHODS: Twenty-eight healthy volunteers were prospectively recruited for coronary MRA at 3T using a steady state injection technique for 3D radial whole heart image acquisition with retrospective respiratory self-gating (ClinicalTrials.gov identifier: NCT01853592). Nineteen volunteers completed both single- and double-dose imaging instances (0.03 and 0.06 mmol/kg, respectively). Intra-individual comparison of image quality was assessed by measurement of apparent signal/contrast-to-noise ratio (aSNR/aCNR) and subjective evaluation of image quality by 2 independent reviewers. RESULTS: The average duration of coronary MRA acquisition was 7.2 +/- 1.2 min. There was significantly higher (60 %, p < 0.001) aSNR of the aorta and right/left ventricle for the double dose compared to single dose injection scheme and aSNR of the coronary arteries increased by 70 % (p < 0.001) for the double dose injection. aCNR increased by +55 % and +60 % in the ventricles and coronary arteries, respectively (p < 0.001). Overall segmental artery visualization for single dose was possible 47 % of the time, which improved to 60 % with double dose (p = 0.019), predominantly driven by improvements in more distal segment visualization (+40 % improvement in mid arterial segments, p = 0.013). CONCLUSIONS: Gadofosveset trisodium dose of 0.06 mmol/kg significantly quantitatively and qualitatively improves the coronary artery image quality compared to 0.03 mmol/kg at 3T for moderate duration (6-8 min) steady state contrast enhanced coronary MRA. PMID- 27004535 TI - Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo. AB - In the past decade, studies have revealed that the phosphatase and tensin homolog (PTEN) protein, a tumor suppressor, comprises a potential biological marker and therapeutic target for esophageal squamous cell carcinoma (ESCC). As such, the delivery of the PTEN gene represents a powerful strategy for ESCC therapy. The tegument protein VP22 of herpes simplex virus type 1 (HSV-1) has been reported to act as a transporter of heterologous proteins across the host cell membrane, thereby enhancing the biological functions of these proteins. In the present study, the intercellular delivery and antitumor activity of the fusion protein PTEN-VP22 were examined in the esophageal squamous cell carcinoma cell line Eca109 both in vitro and in vivo. VP22-mediated PTEN intercellular delivery was confirmed in the Eca109 cells by western blot analysis and by quantitation of immunofluorescence. VP22 alone did not exert antiproliferative effects or induce cell cycle arrest, induction of apoptosis, blockage of the Akt and focal adhesion kinase (FAK) pathways, tumor growth inhibition, or antiangiogenic effects in Eca109 cells. However, compared with PTEN alone, PTEN-VP22 exerted significantly higher antiproliferative effects and induced cell cycle arrest at G1 stage, apoptosis and antiangiogenic effects in Eca109 cells. Together, our findings demonstrate that VP22 alone does not exert antitumor activity directly; however, this protein mediates the intercellular delivery of PTEN and thereby increases its intracellular concentration to achieve a therapeutic steady state, leading to an overall increase in the antitumor activity of PTEN. This study provides further experimental data to confirm the potential of VP22-based intercellular delivery strategies for enhancing the efficacy of gene therapy for cancer treatment. PMID- 27004536 TI - Amphiphilic Graft Copolymer Nanospheres: From Colloidal Self-Assembly to CO2 Capture Membranes. AB - Colloidal nanosphere self-assembly effectively generates ordered nanostructures, prompting tremendous interest in many applications such as photonic crystals and templates for inverse opal fabrication. Here we report the self-assembly of low cost, graft copolymer nanospheres for CO2 capture membranes. Specifically, poly(dimethylsiloxane)-graft-poly(4-vinylpyridine) (PDMS-g-P4VP) is synthesized via one-pot, free radical dispersion polymerization to give discrete monodisperse nanospheres. These nanospheres comprise a surface-anchored highly permeable PDMS layer and internal CO2-philic P4VP spherical core. Their diameter is controllable below the submicrometer range by varying grafting ratios. The colloidal dispersion forms a long-range, close-packed hexagonal array on a substrate by inclined deposition and convective assembly. The array shows dispersion medium dependent packing characteristics. A thermodynamic correlation is determined using different solvents to obtain stable PDMS-g-P4VP dispersions and interpreted in terms of Flory-Huggins interaction parameter. As a proof-of-concept, the implementation of these nanospheres into membranes simultaneously enhances the CO2 permeability and CO2/N2 selectivity of PDMS-based transport matrixes. Upon physical aging of the solution, the CO2/N2 selectivity is improved up to 26, one of the highest values for highly permeable PDMS-based polymeric membranes. PMID- 27004534 TI - The relationship between omega-3 and smoking habit: a cross-sectional study. AB - BACKGROUND: Omega3 polyunsaturated fatty acids (PUFAs) are related to several diseases, including smoking. The aim of this study was to evaluate the relationship between omega-3 intake and tobacco smoking, taking into account the qualitative differences in dietary intake between smokers and non-smokers, the amount of the ingested PUFA and their red blood (RBC) contents. We also looked for an association between omega-3 RBC content and smoking, and also between omega3 intake and the level of nicotine dependence. METHODS: Using a cross sectional study, we included 50 current smokers (group I) and 50 lifetime non smokers (group II), aged 18-75 years. We screened them at the Toronto Western Hospital and the Centre for Addiction and Mental Health (Toronto, Canada). The subjects completed a questionnaire with demographic data, lifestyle habits and details of food intake. The PUFAs measured in the RBC membranes were alphalinolenic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). In order to perform an adjusted comparison between smokers and non-smokers we used the ANCOVA model. RESULTS: After adjusting for confounding factors, non-smokers showed higher consumption of PUFAs, especially salmon: 800 g (0-7.740) than smokers 430 g (0-2.150) P < 0.001. They also had higher DHA levels compared to smokers: 4.81% (2.79-10.21) and 4.13% (2.33-7.73), respectively, p < 0.05. The other PUFAs showed no significant differences between the two groups. CONCLUSIONS: Smokers ate less fish rich in omega3 fatty acids than non-smokers, showing and inverse and significant relationship between omega3 intake and smoking. Smokers had lower levels of DHA and EPA, a not previously reported finding. Considering that PUFAs probably interfere in smoking habit, the increase in omega-3 consumption may become a perspective in prevention or treatment of smoking. However, this inference must be evaluated through specific studies. PMID- 27004538 TI - A giant adult paratesticular rhabdomyosarcomar. PMID- 27004537 TI - Perineural invasion status, Gleason score and number of positive cores in biopsy pathology are predictors of positive surgical margin following laparoscopic radical prostatectomy. AB - This study was designed to define possible preoperative predictors of positive surgical margin after laparoscopic radical prostatectomy. We retrospectively analyzed the records of 296 patients with prostate cancer diagnosed by prostate biopsy, and eventually treated with laparoscopic radical prostatectomy. The prognostic impact of age, prostate volume, preoperative prostate-specific antigen, biopsy Gleason score, maximum percentage tumor per core, number of positive cores, biopsy perineural invasion, capsule invasion on imaging, and tumor laterality on surgical margin was assessed. The overall positive surgical margin rate was 29.1%. Gleason score, number of positive cores, perineural invasion, tumor laterality in the biopsy specimen, and prostate volume significantly correlated with risk of positive surgical margin by univariate analysis (P < 0.05). Gleason score (odds ratio [OR] = 2.286, 95% confidence interval [95% CI] = 1.431-3.653, P = 0.001), perineural invasion (OR = 4.961, 95% CI = 2.656-9.270, P < 0.001), and number of positive cores (OR = 4.403, 95% CI = 1.878-10.325, P = 0.001) were independent predictors of positive surgical margin at the multivariable logistic regression analysis. Patients with perineural invasion, higher biopsy Gleason scores and/or a large number of positive cores in biopsy pathology had more possibility of capsule invasion. The positive surgical margin rate in patients with capsule invasion (49.5%) was much higher than that with localized disease (17.8%). In contrast, prostate volume showed a protective effect against positive surgical margin (OR = 0.572, 95% CI = 0.346-0.945, P = 0.029). Gleason score, perineural invasion, and number of positive cores in the biopsy specimen were preoperative independent predictors of positive surgical margin after laparoscopic radical prostatectomy while prostate volume was a protective factor against positive surgical margin. PMID- 27004540 TI - Corrigendum to "Relapse of prostate cancer from the viewpoint of total gland volume kinetics theory" by Hiroki Watanabe. AB - [This corrects the article DOI: 10.4103/1008-682X.153543.] In published paper by Watanabe, the [Figure 3] on page 905 is incorrect, because of a mistake on computer processing. The correct [Figure 3] follows. The author apologizes to the readers for this careless mistake. PMID- 27004539 TI - Metabolic syndrome in White-European men presenting for secondary couple's infertility: an investigation of the clinical and reproductive burden. AB - We aimed to determine the impact of metabolic syndrome (MetS) on reproductive function in men with secondary infertility, a condition that has received relatively little attention from researchers. Complete demographic, clinical, and laboratory data from 167 consecutive secondary infertile men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorised 0 vs 1 vs 2 or higher). NCEP-ATP III criteria were used to define MetS. Semen analysis values were assessed based on the 2010 World Health Organization (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and MetS. MetS was found in 20 (12%) of 167 men. Patients with MetS were older (P < 0.001) and had a greater BMI (P < 0.001) compared with those without MetS. MetS patients had lower levels of total testosterone (P = 0.001), sex hormone-binding globulin, inhibin B, and anti-Momicronllerian hormone (all P <= 0.03), and they were hypogonadal at a higher prevalence (P = 0.01) than patients without MetS. Moreover, MetS patients presented lower values of semen volume, sperm concentration, and sperm normal morphology (all P <= 0.03). At multivariate logistic regression analysis, no parameters predicted sperm concentration, normal sperm morphology, and total progressive motility. Our data show that almost 1 of 8 White-European men presenting for secondary couple's infertility is diagnosed with MetS. MetS was found to be associated with a higher prevalence of hypogonadism, decreased semen volume, decreased sperm concentration, and normal morphology in a specific cohort of White-European men. PMID- 27004541 TI - A comparison of genetic risk score with family history for estimating prostate cancer risk. AB - Prostate cancer (PCa) testing is recommended by most authoritative groups for high-risk men including those with a family history of the disease. However, family history information is often limited by patient knowledge and clinician intake, and thus, many men are incorrectly assigned to different risk groups. Alternate methods to assess PCa risk are required. In this review, we discuss how genetic variants, referred to as PCa-risk single-nucleotide polymorphisms, can be used to calculate a genetic risk score (GRS). GRS assigns a relatively unique value to all men based on the number of PCa-risk SNPs that an individual carries. This GRS value can provide a more precise estimate of a man's PCa risk. This is particularly relevant in situations when an individual is unaware of his family history. In addition, GRS has utility and can provide a more precise estimate of risk even among men with a positive family history. It can even distinguish risk among relatives with the same degree of family relationships. Taken together, this review serves to provide support for the clinical utility of GRS as an independent test to provide supplemental information to family history. As such, GRS can serve as a platform to help guide-shared decision-making processes regarding the timing and frequency of PCa testing and biopsies. PMID- 27004542 TI - Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging. AB - Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging. PMID- 27004544 TI - [The first LENUS pro(r) pump implantation in Poland in patient with pulmonary hypertension]. PMID- 27004545 TI - [New right bundle branch block after heart transplant as sign of subclinical rejection]. PMID- 27004543 TI - Prevalence of lipid abnormalities in Poland. The NATPOL 2011 survey. AB - BACKGROUND: Poland represents a country of high cardiovascular (CV) risk. The association between lipid abnormalities and increased CV risk is well established. Therefore, it is important to monitor the prevalence and control of dyslipidaemia. AIM: To evaluate serum lipids concentrations as well as the prevalence, awareness, and control of lipid abnormalities in a representative sample of adults in Poland. METHODS: In 2011, in a national cross-sectional survey blood samples were collected from 1168 males and 1245 females, aged 18-79 years, for measurement of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in blood serum. Low density lipoprotein cholesterol (LDL-C) was calculated using Friedewald's formula. RESULTS: Mean serum TC concentration was 197.1 mg/dL (95% CI 193.8-200.4) in males (M) and 198.6 mg/dL (95% CI 195.7-201.5) in females (F). Levels of LDL-C were 123.6 mg/dL (120.9-126.2) and 123.7 mg/dL (121.4-126.1), HDL-C - 45.8 mg/dL (44.7-47.0) and 54.1 mg/dL (53.1-55.1), TG - 140.9 mg/dL (133.0-148.8) and 104.0 mg/dL (99.8-108.2) for males and females, respectively. TC >= 190 mg/dL was found in 54.3% subjects (M 54.3%; F 54.4%). After adding patients on lipid-lowering treatment, hypercholesterolaemia was present in 61.1% of adults (M 60.8%; F 61.3%). LDL-C >= 115 mg/dL was detected in 57.8% of all subjects (M 58.3%; F 57.3%), while HDL-C < 40 mg/dL in 35.2% of males and < 45 mg/dL in 22% of females TG >= 150 mg/dL was found in 21.1% of subjects (M 28.4%; F 14.0%). The highest prevalence of elevated TC and LDL-C levels was present in the age group of 40-59 year-olds. Of those with hypercholesterolaemia 58.7% (M 61.5%, F 56.0%) were not aware of the condition; 22.0% (M 21.0%, F 24.5%) were aware but were not being treated; 8.1% (M 7.7%, F 8.5%) were treated but with TC >= 190 mg/dL; and only 10.9% (M 10.7%, F 11.0%) were being treated with TC < 190 mg/dL. CONCLUSIONS: The prevalence of dyslipidaemia in Poland continues to be high--over 60% of adults have hypercholesterolaemia, and control remains poor. The results of the NATPOL 2011 survey call for urgent preventive measures. PMID- 27004546 TI - Loeffler endocarditis in a patient with non-Hodgkin's lymphoma. PMID- 27004547 TI - Left anterior descending coronary artery fistula into the left atrial appendage. PMID- 27004548 TI - [Coarctation of the aorta--perinatal evolution of the defect]. PMID- 27004549 TI - Left brachiocephalic vein occlusion in a patient with ascending aortic aneurysm: the dilemma of pacemaker implantation. PMID- 27004550 TI - Wurtzite GaAs Quantum Wires: One-Dimensional Subband Formation. AB - It is of contemporary interest to fabricate nanowires having quantum confinement and one-dimensional subband formation. This is due to a host of applications, for example, in optical devices, and in quantum optics. We have here fabricated and optically investigated narrow, down to 10 nm diameter, wurtzite GaAs nanowires which show strong quantum confinement and the formation of one-dimensional subbands. The fabrication was bottom up and in one step using the vapor-liquid solid growth mechanism. Combining photoluminescence excitation spectroscopy with transmission electron microscopy on the same individual nanowires, we were able to extract the effective masses of the electrons in the two lowest conduction bands as well as the effective masses of the holes in the two highest valence bands. Our results, combined with earlier demonstrations of thin crystal phase nanodots in GaAs, set the stage for the fabrication of crystal phase quantum dots having full three-dimensional confinement. PMID- 27004551 TI - Deciphering the transcriptional regulation and spatiotemporal distribution of immunity response in barley to Pyrenophora graminea fungal invasion. AB - BACKGROUND: Barley leaf stripe disease, caused by the fungus Pyrenophora graminea (Pg), is a worldwide crop disease that results in significant loss of barley yield. The purpose of the present work was to use transcriptomic profiling to highlight barley genes and metabolic pathways affected or altered in response to Pg infection and consequently elucidate their involvement and contribution in resistance to leaf stripe. RESULTS: Our study examined and compared the transcriptomes of two barley genotypes using an established differential display reverse-transcription polymerase chain reaction (DDRT-PCR) strategy at 14 and 20 days post-inoculation (dpi). A total of 54 significantly modulated expressed sequence tags (ESTs) were identified. The analysis of gene expression changes during the course of infection with Pg suggested the involvement of 15 upregulated genes during the immunity response. By using network-based analyses, we could establish a significant correlation between genes expressed in response to Pg invasion. Microscopic analysis and quantitative PCR (qPCR) profiling of callose synthase and cellulose synthases revealed a direct involvement of cell wall reinforcement and callose deposition in the Pg-resistant phenotype. CONCLUSIONS: We have identified a number of candidate genes possibly involved in the host-pathogen interactions between barley and Pg fungus, 15 of which are specifically expressed in Pg-resistant plants. Collectively, our results suggest that the resistance to leaf stripe in barley proceeds through callose deposition and different oxidation processes. PMID- 27004552 TI - Caring touch as a bodily anchor for patients after sustaining a motor vehicle accident with minor or no physical injuries - a mixed methods study. AB - BACKGROUND: Patients who sustain a motor vehicle accident may experience long term distress, even if they are uninjured or only slightly injured. There is a risk of neglecting patients with minor or no physical injuries, which might impact future health problems. The aim of this study was to explore patients' subjective experiences and perspectives on pain and other factors of importance after an early nursing intervention consisting of "caring touch" (tactile massage and healing touch) for patients subjected to a motor vehicle accident with minor or no physical injuries. METHODS: A mixed method approach was used. The qualitative outcomes were themes derived from individual interviews. The quantitative outcomes were measured by visual analogue scale for pain (VAS, 0 100), sense of coherence (SOC), post-traumatic stress (IES-R) and health status (EQ-5D index and EQ-5D self-rated health). Forty-one patients of in total 124 eligible patients accepted the invitation to participate in the study. Twenty seven patients completed follow-up after 6 months whereby they had received up to eight treatments with either tactile massage or healing touch. RESULTS: Patients reported that caring touch may assist in trauma recovery by functioning as a physical "anchor" on the patient's way of suffering, facilitating the transition of patients from feeling as though their body is "turned off" to becoming "awake". By caring touch the patients enjoyed a compassionate care and experience moments of pain alleviation. The VAS pain ratings significantly decreased both immediately after the caring touch treatment sessions and over the follow-up period. The median scores for VAS (p < 0.001) and IES-R (p 0.002) had decreased 6 months after the accident whereas the EQ-5D index had increased (p < 0.001). There were no statistically significant differences of the SOC or EQ-5D self rated health scores over time. CONCLUSIONS: In the care of patients suffering from a MVA with minor or no physical injuries, a caring touch intervention is associated with patients' report of decreased pain and improved wellbeing up to 6 months after the accident. TRIAL REGISTRATION: ClinicalTrials.gov Id: NCT02610205 . Date 25 November 2015. PMID- 27004553 TI - Electrophysiological behavior of neonatal astrocytes in hippocampal stratum radiatum. AB - BACKGROUND: Neonatal astrocytes are diverse in origin, and undergo dramatic change in gene expression, morphological differentiation and syncytial networking throughout development. Neonatal astrocytes also play multifaceted roles in neuronal circuitry establishment. However, the extent to which neonatal astrocytes differ from their counterparts in the adult brain remains unknown. RESULTS: Based on ALDH1L1-eGFP expression or sulforhodamine 101 staining, neonatal astrocytes at postnatal day 1-3 can be reliably identified in hippocampal stratum radiatum. They exhibit a more negative resting membrane potential (V M), -85 mV, than mature astrocytes, -80 mV and a variably rectifying whole-cell current profile due to complex expression of voltage-gated outward transient K(+) (IKa), delayed rectifying K(+) (IKd) and inward K(+) (IKin) conductances. Differing from NG2 glia, depolarization-induced inward Na(+) currents (INa) could not be detected in neonatal astrocytes. A quasi physiological V M of -69 mV was retained when inwardly rectifying Kir4.1 was inhibited by 100 MUM Ba(2+) in both wild type and TWIK-1/TREK-1 double gene knockout astrocytes, indicating expression of additional leak K(+) channels yet unknown. In dual patch recording, electrical coupling was detected in 74 % (14/19 pairs) of neonatal astrocytes with largely variable coupling coefficients. The increasing gap junction coupling progressively masked the rectifying K(+) conductances to account for an increasing number of linear voltage-to-current relationship passive astrocytes (PAs). Gap junction inhibition, by 100 MUM meclofenamic acid, substantially reduced membrane conductance and converted all the neonatal PAs to variably rectifying astrocytes. The low density expression of leak K(+) conductance in neonatal astrocytes corresponded to a ~50 % less K(+) uptake capacity compared to adult astrocytes. CONCLUSIONS: Neonatal astrocytes predominantly express a variety of rectifying K(+) conductances, form discrete cell-to-cell gap junction coupling and are deficient in K(+) homeostatic capacity. PMID- 27004554 TI - Influence of the amino acid residues at 70 in M protein of porcine reproductive and respiratory syndrome virus on viral neutralization susceptibility to the serum antibody. AB - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is mainly responsible for the significant economic losses in pig industry in the world. The adaptive immune responses of the host act as an important source of selective pressure in the evolutionary process of the virus. In the previous study, we confirmed that the amino acid (aa) residues at 102 and 104 sites in GP5 played an important role in escaping from the neutralizing antibodies (NAbs) against highly pathogenic PRRSV (HP-PRRSV). In this study, we further analyzed the aa mutants affecting neutralization susceptibility of NAbs in other structure proteins in NAbs resistant variants. METHODS: Based on the different aa residues of the structural proteins between the resistant virus BB20s and the parent virus BB, 12 recombinant PRRSV strains containing these aa residue substitutions were constructed using reverse genetic techniques. The neutralizing antibody (NA) titers of the recombinant strains were tested on MARC-145 and porcine alveolar macrophages (PAMs). And the NAbs binding abilities of parent and rescued viruses were tested by using ELISA method. RESULTS: By using the neutralization assay, it was revealed that the NA titer of N4 serum with rBB/Ms was significantly lower than that with rBB. Meanwhile, NA titer of the serum with rBB20s/M was significantly higher than that with rBB20s. The ELISA binding results showed that rBB/Ms had higher binding inability to N4 than did rBB. And alignment of M protein revealed that the variant aa residue lysine (K) at 70 was also existed in field type 2 and vaccine PRRSV strains. CONCLUSIONS: The aa residue at 70 in M protein of PRRSV played an important role in regulating neutralization susceptibility to the porcine serum NAbs. It may be helpful for monitoring the antigen variant strains in the field and developing new vaccine against PRRSV in the future. PMID- 27004555 TI - Soy isoflavones and glucose metabolism in menopausal women: A systematic review and meta-analysis of randomized controlled trials. AB - SCOPE: The aim of this meta-analysis was to investigate whether soy isoflavones, a type of phytoestrogen, would affect glucose homeostasis in menopausal women. METHODS AND RESULTS: Studies concerning about the relationship between soy isoflavone treatment and glucose metabolism were searched on MEDLINE and WEB OF SCIENCE (updated through April 2015) and EMBASE (1990-April 2015). Seventeen randomized controlled trials (RCTs) with a total number of 1529 menopausal women were identified for meta-analysis. Soy isoflavones were found to show great significance for the improvement of glucose metabolism, though marked heterogeneity was found between studies. The overall results showed that the average difference in fasting blood glucose values between women assigned to soy isoflavones and women in placebo groups was -0.22 mmol/L (95% CI: -0.38 to -0.07 mmol/L) under a random-effects model. In addition, the effect of soy isoflavones on insulin was also significant: -0.43 MUIU/mL (95% CI: -0.71 to -0.14 MUIU/mL), as was the effect on homeostasis model assessment insulin resistance (HOMA-IR): 0.52 (95% CI: -0.76 to -0.28). CONCLUSION: Although the results displayed a significant tendency in favor of soy isoflavones, it appears that genistein alone played an important role in improving glucose metabolism due to its low heterogeneity. PMID- 27004556 TI - The impact of migration on tuberculosis epidemiology and control in high-income countries: a review. AB - Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub optimal treatment completion will need to be addressed to ensure program efficacy. PMID- 27004557 TI - Factors associated with Anaplasma spp. seroprevalence among dogs in the United States. AB - BACKGROUND: Dogs in the United States are hosts to a diverse range of ticks and tick-borne pathogens, including A. phagocytophilum, an important emerging canine and human pathogen. Previously, a Companion Animal Parasite Council (CAPC) sponsored workshop proposed factors purported to be associated with the infection risk for tick-transmitted pathogens in dogs in the United States, including climate conditions, socioeconomic characteristics, local topography, and vector distribution. METHODS: Approximately four million test results from routine veterinary diagnostic tests from 2011-2013, which were collected on a county level across the contiguous United States, are statistically analyzed with the proposed factors via logistic regression and generalized estimating equations. Spatial prevalence maps of baseline Anaplasma spp. prevalence are constructed from Kriging and head-banging smoothing methods. RESULTS: All of the examined factors, with the exception of surface water coverage, were significantly associated with Anaplasma spp. prevalence. Overall, Anaplasma spp. prevalence increases with increasing precipitation and forestation coverage and decreases with increasing temperature, population density, relative humidity, and elevation. Interestingly, socioeconomic status and deer/vehicle collisions were positively and negatively correlated with canine Anaplasma seroprevalence, respectively. A spatial map of the canine Anaplasma hazard is an auxiliary product of the analysis. Anaplasma spp. prevalence is highest in New England and the Upper Midwest. CONCLUSIONS: The results from the two posited statistical models (one that contains an endemic areas assumption and one that does not) are in general agreement, with the major difference being that the endemic areas model estimates a larger prevalence in Western Texas, New Mexico, and Colorado. As A. phagocytophilum is zoonotic, the results of this analysis could also help predict areas of high risk for human exposure to this pathogen. PMID- 27004558 TI - High-density lipopoprotein antioxidant capacity, subpopulation distribution and paraoxonase-1 activity in patients with systemic lupus erythematosus. AB - BACKGROUND: The causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients. METHODS: Lipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein 1 levels were determined. RESULTS: HDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 +/- 26.87 vs. 148.35 +/- 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 +/- 58.28% vs. 217.71 +/- 54.36%, p < 0.001) were significantly reduced in patients compared to controls. Additionally, all HDL subfraction concentrations were significantly decreased in patients, while the levels of the examined inflammatory markers were significantly elevated in SLE subjects. The latter correlated positively with disease activity, and negatively with HDL concentration and total HDL antioxidant capacity, respectively. PON1 arylesterase activity and erythrocyte sedimentation rate were independent predictors of total HDL antioxidant capacity. CONCLUSIONS: Induced by the systemic inflammation, altered composition and antioxidant activity may diminish the anti-atherogenic effect of HDL and therefore may contribute to the increased cardiovascular risk of SLE patients. PMID- 27004561 TI - Development of the Biopen: a handheld device for surgical printing of adipose stem cells at a chondral wound site. AB - We present a new approach which aims to translate freeform biofabrication into the surgical field, while staying true to the practical constraints of the operating theatre. Herein we describe the development of a handheld biofabrication tool, dubbed the 'biopen', which enables the deposition of living cells and biomaterials in a manual, direct-write fashion. A gelatin methacrylamide/hyaluronic acid-methacrylate (GelMa/HAMa) hydrogel was printed and UV crosslinked during the deposition process to generate surgically sculpted 3D structures. Custom titanium nozzles were fabricated to allow printing of multiple ink formulations in a collinear (side-by-side) geometry. Independently applied extrusion pressure for both chambers allows for geometric control of the printed structure and for the creation of compositional gradients. In vitro experiments demonstrated that human adipose stem cells maintain high viability (>97%) one week after biopen printing in GelMa/HAMa hydrogels. The biopen described in this study paves the way for the use of 3D bioprinting during the surgical process. The ability to directly control the deposition of regenerative scaffolds with or without the presence of live cells during the surgical process presents an exciting advance not only in the fields of cartilage and bone regeneration but also in other fields where tissue regeneration and replacement are critical. PMID- 27004560 TI - ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. AB - Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic inflammatory skin disease of children and adults. The diagnosis is made using evaluated clinical criteria. Disease activity is best measured with a composite score assessing both objective signs and subjective symptoms, such as SCORAD. The management of AD must consider the clinical and pathogenic variabilities of the disease and also target flare prevention. Basic therapy includes hydrating topical treatment, as well as avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment of visible skin lesions is based on topical glucocorticosteroids and the topical calcineurin inhibitors tacrolimus and pimecrolimus. Topical calcineurin inhibitors are preferred in sensitive locations. Tacrolimus and mid-potent steroids are proven for proactive therapy, which is long-term intermittent anti-inflammatory therapy of the frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is indicated for severe refractory cases. Biologicals targeting key mechanisms of the atopic immune response are promising emerging treatment options. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) may diminish pruritus, but do not have sufficient effect on lesions. Adjuvant therapy includes UV irradiation, preferably UVA1 or narrow-band UVB 311 nm. Dietary recommendations should be patient specific and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. 'Eczema school' educational programmes have been proven to be helpful for children and adults. PMID- 27004559 TI - HCV-induced miR146a controls SOCS1/STAT3 and cytokine expression in monocytes to promote regulatory T-cell development. AB - Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up-regulated in monocytes from hepatitis C virus (HCV)-infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll-like receptor (TLR) stimulation. This miR146a induction by HCV infection and differential response to TLR stimulation were recapitulated in vitro in monocytes co-cultured with hepatocytes with or without HCV infection. Importantly, inhibition of miR146a in monocytes from HCV infected patients led to a decrease in IL-23, IL-10 and TGF-beta expressions through the induction of suppressor of cytokine signalling 1 (SOCS1) and the inhibition of signal transducer and activator transcription 3 (STAT3), and this subsequently resulted in a decrease in regulatory T cells (Tregs) accumulated during HCV infection. These results suggest that miR146a may regulate SOCS1/STAT3 and cytokine signalling in monocytes, directing T-cell differentiation and balancing immune clearance and immune injury during chronic viral infection. PMID- 27004562 TI - Simultaneous mutations of LAMB2 and NPHP1genes in a Chinese girl with isolated congenital nephrotic syndrome: a case report. AB - BACKGROUND: LAMB2 mutations cause Pierson syndrome (OMIM 609049), an autosomal recessive genetic disease typically characterized by congenital nephrotic syndrome (CNS) and early onset renal failure, as well as bilateral microcoria. NPHP1 mutations cause familial juvenile nephronophthisis type 1 (NPHP1, OMIM 256100), another autosomal recessive renal disease that usually occurs years after birth. Both Pierson syndrome and nephronophthisis cause end-stage renal disease and rare kidney diseases in children. We report an extremely rare case of concurrent mutations of LAMB2 and NPHP1 in a Chinese girl with isolated CNS and the association of the phenotype with novel non-truncating mutations of LAMB2. CASE PRESENTATION: A-34-day-old girl presented with CNS but no eye abnormalities, and mild hyperechogenicity of kidneys. A novel c.1176_1178delTCT mutation caused deletion of a glycine in exon 9 of LAMB2, and another mutation c.4923 + 2 T > G led to a splicing error. In addition, compound heterozygous mutations of NPHP1 were identified in this child using next generation sequencing, and confirmed by Sanger sequencing. CONCLUSION: Mutations of the LAMB2 and NPHP1 are present in infants with isolated CNS. Next generation sequencing enabled high-throughput screening for mutant genes promptly, with clinically significant outcomes. In addition, our results expand the phenotype spectrum of LAMB2 mutations as the only renal manifestation. PMID- 27004563 TI - Prevalence and associating factors of atrial fibrillation in patients with hypertension: a nation-wide study. AB - BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia and increases risk of ischemic stroke. Data on the prevalence of AF in Thailand is lacking especially in patients with hypertension. The objectives of this study were to determine prevalence of AF in patients with hypertension and to determine factors that are associated with increased prevalence of AF in a multicenter nationwide study. METHODS: A cross-sectional survey for the national outcome evaluation among hypertensive patients visiting 831 public hospitals in Thailand was conducted between 2011 and 2012 to evaluate status of standard care in hypertensive patients visiting public Thailand Ministry of Public Health (MoPH) hospitals. Inclusion criteria were hypertensive patients aged at least 20 years who had received medical care in the targeted hospital for at least 12 months. The main outcome measurement was AF rhythm, and was measured along with potential risk factors age, gender and cardiovascular risk factors. RESULTS: There were 13207 hypertensive patients who had ECG data recorded during the survey. AF was detected in 457 patients (3.46 %). Prevalence of AF increased with increasing age, was more common in males and in patients with chronic kidney disease (CKD). Multivariable modelling was conducted to assess which factors were most associated with increased prevalence of AF, and the results showed older age followed by male gender, low LDL-cholesterol and increased uric acid levels were the most important risk factors for AF in this population. CONCLUSIONS: Prevalence of AF in hypertensive patients was 3.46 %. Factors associated with increased risk of AF are old age, male gender, low LDL-cholesterol and elevated uric acid level. PMID- 27004564 TI - The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder. AB - OBJECTIVE: The aim of the present study was to characterize the neurocognitive effects of lithium in bipolar disorder to inform clinical and research approaches for further investigation. METHODS: Key words pertaining to neurocognition in bipolar disorder and lithium treatment were used to search recognized databases to identify relevant literature. The authors also retrieved gray literature (e.g., book chapters) known to them and examined pertinent articles from bibliographies. RESULTS: A limited number of studies have examined the effects of lithium on neurocognition in bipolar disorder and, although in some domains a consistent picture emerges, in many domains the findings are mixed. Lithium administration appears to reshape key components of neurocognition - in particular, psychomotor speed, verbal memory, and verbal fluency. Notably, it has a sophisticated neurocognitive profile, such that while lithium impairs neurocognition across some domains, it seemingly preserves others - possibly those vulnerable to the effects of bipolar disorder. Furthermore, its effects are likely to be direct and indirect (via mood, for example) and cumulative with duration of treatment. Disentangling the components of neurocognition modulated by lithium in the context of a fluctuating and complex illness such as bipolar disorder is a significant challenge but one that therefore demands a stratified and systematic approach, such as that provided by the Lithium Battery. CONCLUSIONS: In order to delineate the effects of lithium therapy on neurocognition in bipolar disorder within both research and clinical practice, a greater understanding and measurement of the relatively stable neurocognitive components is needed to examine those that indeed change with lithium treatment. In order to achieve this, we propose a Lithium Battery-Clinical and a Lithium Battery-Research that can be applied to these respective settings. PMID- 27004565 TI - Bimetallic Gold(I) Complexes with Ethynyl-Helicene and Bis-Phosphole Ligands: Understanding the Role of Aurophilic Interactions in their Chiroptical Properties. AB - Monometallic gold(I)-alkynyl-helicene complexes (1 a,b) and bimetallic gold(I) alkynyl-helicene architectures featuring the presence (2 a,b) or absence (3 a,b) of aurophilic intramolecular interactions were prepared by using different types of phosphole ligands (mono-phosphole L1 or bis-phospholes L2,3). The influence of the Au(I) d(10) metal center(s) on the electronic, photophysical, and chiroptical properties of these unprecedented phosphole-gold(I)-alkynyl-helicene complexes was examined. Experimental and theoretical results highlight the importance of ligand-to-ligand-type charge transfers and the strong effect of the presence or absence of Au(I) -Au(I) interactions in 2 a,b. PMID- 27004566 TI - Invasive Streptococcus mutans induces inflammatory cytokine production in human aortic endothelial cells via regulation of intracellular toll-like receptor 2 and nucleotide-binding oligomerization domain 2. AB - Streptococcus mutans, the primary etiologic agent of dental caries, can gain access to the bloodstream and has been associated with cardiovascular disease. However, the roles of S. mutans in inflammation in cardiovascular disease remain unclear. The aim of this study was to examine cytokine production induced by S. mutans in human aortic endothelial cells (HAECs) and to evaluate the participation of toll-like receptors (TLRs) and cytoplasmic nucleotide-binding oligomerization domain (NOD) -like receptors in HAECs. Cytokine production by HAECs was determined using enzyme-linked immunosorbent assays, and the expression of TLRs and NOD-like receptors was evaluated by real-time polymerase chain reaction, flow cytometry and immunocytochemistry. The involvement of TLR2 and NOD2 in cytokine production by invaded HAECs was examined using RNA interference. The invasion efficiencies of S. mutans strains were evaluated by means of antibiotic protection assays. Five of six strains of S. mutans of various serotypes induced interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production by HAECs. All S. mutans strains upregulated TLR2 and NOD2 mRNA levels in HAECs. Streptococcus mutans Xc upregulated the intracellular TLR2 and NOD2 protein levels in HAECs. Silencing of the TLR2 and NOD2 genes in HAECs invaded by S. mutans Xc led to a reduction in interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production. Cytokine production induced by invasive S. mutans via intracellular TLR2 and NOD2 in HAECs may be associated with inflammation in cardiovascular disease. PMID- 27004567 TI - Letter to the editor about "Effects of fruit and vegetables on metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials" by Shin JY, Kim JY, Kang HT, Han KH, Shim JY published online in 2015 May 6. AB - The letter to the editor presents methodological issues about the search strategy, adequate reporting of meta-analysis, and statistical details of the referred article. PMID- 27004568 TI - Harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways. AB - Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala, possesses both antitumor and anti-nociceptive effects and inhibits human DNA topoisomerase. However, no detailed data are available concerning the mechanisms of harmine in human colorectal carcinoma SW620 cells. In the present study, we demonstrated that harmine inhibited the proliferation of SW620 cells in a dose dependent manner using MTT and clone formation assays, and the IC50 value of harmine on the growth inhibition of SW620 cells for 48 h was 5.13 ug/ml. PI staining showed that harmine altered the cell cycle distribution by decreasing the proportion of cells in the G0-G1 phase and increasing the proportion in the S and G2-M phase. The expression level of cyclin D1 was decreased, while the expression of cyclin A, E2 and B1, CDK1/cdc2, Myt-1 and p-cdc2 (Tyr15) were increased, which was in accordance with the S and G2/M phase arrest. Hoechst 33258 staining revealed nuclear fragmentation, chromosomal condensation and cell shrinkage in the SW620 cells treated with harmine. Flow cytometry revealed that the percentage of apoptotic sub-G1 cells increased from 7.19 to 26.58%, while in the control group, sub-G1 cells only increased from 1.53 to 1.60%. Furthermore, early and late apoptotic cells were increased from 11.96 to 26.38% when incubated with the indicated concentration of harmine for 48 h, while in the control group, <8% of cells underwent apoptosis. JC-1 staining revealed that harmine decreased mitochondrial transmembrane potential (DeltaPsim). The apoptosis of SW620 cells was also detected by western blot analysis, showing caspase-3 and -9, and PARP activation; the downregulation of Bcl-2, Mcl-1, Bcl-xL; and the upregulation of Bax. The expression of p-ERK, p-Akt (Ser473) and p-Akt (Thr308) was inhibited, and phosphorylation of downstream targets of Akt, such as p-FoxO3a and p-GSK 3beta were also attenuated. In conclusion, harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways. PMID- 27004569 TI - Self-Propelling Hydrogel/Emulsion-Hydrogel Soft Motors for Water Purification. AB - We fabricate a kind of catalytic self-propelling hydrogel soft motor (H-motor) via a facile injection loading method with low energy consumption. The factors influencing the practicability of H-motors, including locomotive ability and reusability, are investigated. The succession of rapid bubble evolution and propulsion endows the millimeter-sized columnar H-motors with length/diameter of 1 a remarkable speed of 3.84 mm s(-1) in 10% (w/w) hydrogen peroxide (H2O2) solution. Moreover, the H-motors maintain undiminished propulsion capability and functionality even after repeated loading for 6 times. Additionally, we also fabricate emulsion-hydrogel soft motors (E-H-motors) templated from the oil/water (O/W) emulsion for the first time, which exhibit a faster speed of 4.33 mm s(-1) under the same conditions. It can be ascribed to the additional liberation of low boiling oil phase stored in the emulsion-hydrogels caused by catalytic reaction heat, which is appropriate for larger propulsive situations. The stabilized, efficient, and reusable H-motors are selected for industrial effluents purification to fit the imperious demands about the disposal of organic pollutants in water. The synergy effect between catalytic degradation and enhanced intermixing of the fluid flow around the miniaturized soft motors gives rise to an effective and exhaustive removal of organic contaminants. PMID- 27004571 TI - Geographical variation in reporting Interstitial Lung Disease as an adverse drug reaction: findings from an European Medicines Agency analysis of reports in EudraVigilance. AB - PURPOSE: Clinically, interstitial lung disease (ILD) is a heterogeneous group of over 150 respiratory disorders. In the context of its signal evaluation work, the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has seen geographic clustering of case reports of ILD from Japan. To explore this further, EudraVigilance (EV), the EMA's database of adverse drug reactions (ADRs), was analysed. The results have been used to inform on implications for pharmacovigilance including signal detection and evaluation activities. METHODS: EV was queried for reports of respiratory ADRs coded using MedDRA for the period 1994-2014 for all medicinal products. Descriptive statistics and non-parametric (chi-square) independence tests were produced to compare reporting of ILD from Japan versus the rest of the world. RESULTS: As of 31 December 2014, there were 26 551 case reports of ILD in EV of which 17 526 (66%) originated in Japan. The reporting rate of ILD for Japan has been consistently higher over the period. The odds that a case report from Japan in EV refers to ILD is OR = 20.7, 95% CI 20.2, 21.3 (p < 0.001), compared to OR = 0.60, 95% CI 0.54, 0.67 (p < 0.001) for pulmonary fibrosis. CONCLUSIONS: A geographic imbalance between Japan and the rest of the world in reporting respiratory ADRs as ILD is confirmed. Consequently, the PRAC has developed approaches to address this in relation to signals of ILD it assesses to allow for more targeted risk minimisation including updates to the product information in the EU setting. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27004572 TI - Epidemiology of dengue in Nepal: History of incidence, current prevalence and strategies for future control. AB - Dengue is now established as one of the most important arboviral infections. As the epidemic continues unabated globally, this Aedes mosquito-transmitted pathogen is considered a major re-emerging tropical disease and significant public health concern. Four well-established distinct serotypes of dengue virus, with a fifth one recently proposed, are responsible for causing a spectrum of clinical symptoms in humans ranging from mild fever to severe haemorrhagic manifestations. Indigenous cases of dengue were first recognised in Nepal, a Himalayan country bordered by India and China, just a decade ago in a cluster of tropical and subtropical areas. Subsequently, the range of infection has extended all over the country and now comprises not only low lying regions, but also hilly locations including the capital city Kathmandu. The two major epidemics to date, in 2010 and 2013, have demonstrated the capacity of infection outbreaks to be explosive and challenging to currently available disease control measures. There is a pressing need to undertake effective vector surveillance studies supported by provision of well-equipped diagnostic virology laboratories. However, sincere efforts are being made to map the nationwide prevalence and understand the epidemiology of dengue infection. Yet, the precise burden of dengue in Nepal remains unknown, since most reports are confined to economically affluent areas and do not account for regions of relative social deprivation in which disease is more likely to occur. This review presents a current overview of dengue in Nepal and discusses future prospects for control of this debilitating disease in the country. PMID- 27004573 TI - Laboratory diagnosis of human visceral leishmaniasis. AB - Visceral leishmaniasis (VL), caused by the Leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. VL patients may be asymptomatic or they may present symptoms and findings of a systemic infection. The positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic diseases. The fact that HIV co-infections often produce atypical presentations and the heterogeneity of Leishmania species, which is common in many endemic regions, also complicate the diagnosis. Despite that, some of the parasitological methods are still considered to be the reference standard for VL diagnosis due to their specificity. The development of serological and molecular tests has further enhanced the diagnostic approach of VL. Recombinant antigens have improved the performance of serodiagnostic tests, with DAT and the rK39 antigen based immunochromatographic test being the most appropriate methods for the serological diagnosis of VL. Molecular techniques, despite the fact that their implementation is often difficult and infeasible, have become increasingly relevant due to remarkable sensitivity and specificity, and to the variability of tested samples. Quantitative polymerase chain reaction (qPCR) has been shown to be superior than conventional PCR for the differentiation between active VL and asymptomatic infections, such as for the detection of VL-HIV coinfection. This review summarizes the available methods with their applications in the diagnosis of VL, and focuses on the recent developments in VL diagnostics. PMID- 27004570 TI - Chemotherapy following radium-223 dichloride treatment in ALSYMPCA. AB - BACKGROUND: Radium-223 prolongs overall survival in patients with castration resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance. An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium-223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium-223. METHODS: In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium-223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed. RESULTS: Overall, 142 radium-223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium-223, 72% placebo) and mitoxantrone (16% radium-223, 20% placebo). The majority of patients (61% radium 223, 58% placebo) had received prior docetaxel. Radium-223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium-223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3-4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium-223 versus placebo patients. Median overall survivals from start of chemotherapy were 16.0 and 15.8 months following radium-223 and placebo, respectively. CONCLUSIONS: Chemotherapy following radium-223, regardless of prior docetaxel, is feasible and appears to be well tolerated in patients with CRPC and symptomatic bone metastases. Prostate 76:905-916, 2016. (c) 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID- 27004574 TI - Mosquito adulticidal activity of the leaf extracts of Spondias mombin L. against Aedes aegypti L. and isolation of active principles. AB - BACKGROUND & OBJECTIVES: Aedes aegypti is a domestic mosquito and one of the primary vectors for dengue and yellow fever. Since, it is a vector of deadly diseases, its control becomes essential. Medicinal plants may be an alternative to adulticidal agents since they contain rich source of bioactive compounds. This study was designed to determine the adulticidal activity of Spondias mombin leaf methanol crude extract, n-hexane, dichloromethane and ethyl acetate fractions against female adults of Ae. aegypti mosquitoes and isolate active compound(s) responsible for the bioactivity. METHODS: All leaf extract and fractions were evaluated for adulticidal activity against Ae. aegypti mosquitoes. Adult mortality was observed after 24 h of exposure. The dichloromethane fraction was further purified being the most active fraction using silica gel column chromatography and the active compounds were identified with the aid of HPLC and LC-ESI-MS/MS. The LC50 and LC90 were determined by Probit analysis. RESULTS: Dichloromethane fraction was the most effective fraction with LC50 value of 2172.815 MUg/ml. Compounds identified were mainly ellagic acid and 1-O-Galloyl-6 O-luteoyl-alpha-D-glucose. INTERPRETATION & CONCLUSION: The S. mombin leaf extracts and fractions proved to be a strong candidate for a natural, safe and stable adulticide, alternative to synthetic adulticide. PMID- 27004575 TI - Netting the malaria menace: Distribution and utilization of long-lasting insecticidal net in a malaria endemic area in Bankura, West Bengal. AB - BACKGROUND & OBJECTIVES: Long-lasting insecticidal net (LLIN) is considered to be a highly effective intervention against malaria under National Vector Borne Disease Control Programme in India. A cross-sectional study was undertaken to assess the coverage and utilization of LLIN and the factors related thereto. METHODS: A survey of 1300 households was carried out in Ranibandh block of Bankura district in West Bengal, India, using lot quality assurance sampling (LQAS) method. Coverage/utilization of 80% was considered as minimum acceptable norm. The weighted sample size was calculated from each village of the block. The sociodemographic, economic information of the household along with the availability and use of LLIN was collected through interview and observation. RESULTS: In total, 7320 individuals including 840 children <= 5 yr were visited. Overall coverage of adequate LLIN was 65.4% (+/- 1.5%) and for children <= 5 yr, it was 60.5% (+/- 1.3%). Overall, 66.1% (+/- 1.4%) people of all ages and 63.7% (+/- 1.4%) children <= 5 yr slept under LLINs in the night before the survey. Out of 26 sub-centres, distribution of LLINs in 10 sub-centres was below the accepted norm, whereas utilization was sub-optimal in 19 sub-centres. In only 18.2% (+/- 0.5%) households, LLINs remained hanging during daytime. Poverty, caste, education, perception regarding malarial morbidity and preventive action of LLIN were associated significantly with the distribution of LLIN. Similarly, poverty (AOR = 2.14), threat perception regarding malarial morbidity (AOR = 1.51) and mortality (AOR = 2.52) were positively associated with the use of LLIN. Full utilization of bednets by under-fives of the households was higher in villages with sub-centres. INTERPRETATION & CONCLUSION: Around two-third population of the study area was effectively covered with LLIN. Higher proportion of socially marginalized people received LLIN. Threat perception regarding malaria was directly associated with both receipt and use of LLIN. Behaviour change communication on utilization along with adequate access to LLIN needs to be strengthened. PMID- 27004576 TI - Comparative evaluation of validity and cost-benefit analysis of rapid diagnostic test (RDT) kits in diagnosis of dengue infection using composite reference criteria: A cross-sectional study from south India. AB - BACKGROUND & OBJECTIVES: Rapid diagnostic test (RDT) kits are widely used in India for the diagnosis of dengue infection. It is important to evaluate the validity and reliability of these RDTs. The study was aimed to determine the sensitivity, specificity and predictive value of four commercially available RDTs [Panbio Dengue Duo cassette, Standard Diagnostics (SD) Bioline Dengue Duo, J. Mitra Dengue Day-1 test and Reckon Dengue IgG/IgM] against composite reference criteria (CRC), and compare the cost of the tests. METHODS: In this prospective observational study for diagnostic accuracy, we tested stored blood samples from 132 cases of dengue and 149 controls of other infections as classified based on CRC, with all the four RDTs. The CRC was based on the epidemiological considerations, common clinical features and laboratory abnormalities. The non dengue controls were the cases of proven alternative diagnosis. The diagnostic performances of the tests were compared in terms of sensitivity, specificity and predictive value along with the cost involved per test. RESULTS: The sensitivity of the Panbio and SD RDT kits was found to be 97.7 and 64.3% respectively, and the specificities were 87.8 and 96.6% respectively. The sensitivity of the NS1 antigen capture by SD Duo, Reckon, J. Mitra RDTs was 20.9, 18.6 and 27.1% respectively. The prevalence of dengue specific IgG antibody with Panbio RDT kits was 49.3%. The cost per test for Panbio, SD, Reckon and J. Mitra is US$ 6.90, 4.27, 3.29 and 3.61 respectively. CONCLUSION: It was concluded that in dengue outbreak, Panbio IgM capture RDT alone is reliable and easily available test which can be used in acute phase of dengue infection in any resource limited set up. NS1 capture rates by any of the other three RDTs might not be reliable for the diagnosis of acute dengue infection. PMID- 27004577 TI - Ecdysis period and rate deviations of dengue mosquito vector, Aedes aegypti reared in different artificial water-holding containers. AB - BACKGROUND & OBJECTIVES: Artificial water-holding containers (AWHCs) have been well-documented in many Aedes aegypti studies for dengue surveillance and developmental research. Hence, we investigated the role of different AHWCs on the development and ecdysis period of Ae. aegypti dengue vector, a container breeding mosquito. METHODS: Nine types of AWHCs, namely glass, polystyrene foam, rubber, steel, porcelain, plastic, aluminum, clay and concrete, were chosen for the study. All AWHCs were subjected to the developmental assay for an observation period of 10 days. Regression and hazard analyses were employed to the developmental stages and the characteristics of the AWHCs. RESULTS: The observations revealed that Ae. aegypti development is fastest in glass and polystyrene containers while slowest in concrete containers. Moreover, pupal ecdysis appears to be the most affected by the characteristics of the AWHCs based on regression and hazard analyses. INTERPRETATION & CONCLUSION: Characteristics of the container that can regulate water temperature seem to be the driving force with regards to the slow or fast development of Ae. aegypti, more notably in pupal ecdysis. The results of the study further strengthen our understanding on the dynamics of Ae. aegypti's developmental biology to different characteristics of artificial water containers. This, in turn, would aid in devising vector control strategies against dengue especially in endemic areas. PMID- 27004579 TI - Role of geospatial technology in identifying natural habitat of malarial vectors in South Andaman, India. AB - BACKGROUND & OBJECTIVES: Malaria is a serious disease which has repeatedly threatened Andaman, an island territory of India. Uncharted dense vegetation and inaccessibility are the salient features of the area and the major areas are covered by remotely sensed data to identify the malaria vector's natural habitat. The present investigation appraises the role of geospatial technologies in identifying the natural habitat of malarial vectors. METHODS: The base map was prepared from Survey of India's toposheets, the landuse map was prepared from indices techniques like normalised difference vegetation index (NDVI), normalised difference water index (NDWI), modified normalised difference water index (MNDWI), normalised difference pond index (NDPI), and normalized difference turbidity index (NDTI) in conjugation with visual interpretation. The soil moisture content map was reproduced from the soil atlas of Andaman and Nicobar Islands followed by generation of an aspect profile from ASTER-GDEM satellite data. Both the landuse map and aspect profile were validated for accuracy in the field. RESULTS: A weighted overlay analysis of the classes like landuse, soil moisture and aspect profile of the study area resulted in identification of the potential natural habitat map of malaria vector surrounding the areas of Tushnabad, Garacharma, Manglutan, Chouldari, Ferrargunj and Wimberlygunj hamlets. INTERPRETATION & CONCLUSION: The natural habitat of malaria vector indicated that Tushnabad, Garacharma, Manglutan, Chouldari, Ferrargunj and Wimberlygunj hamlets are within the proximity of 2.5 km from the prime habitat location with more number of malaria positive cases. Also these hamlets are surrounded by dense evergreen forest and the land surface is draped by clay loam and clay soil texture exhibiting high soil moisture content warranting high rates of survival and proliferation of the vector ensuring resurgence of malaria every year. It is thus concluded that application of geospatial technologies plays an important role in identifying the natural habitat of malaria vector. PMID- 27004578 TI - Relationship of annual entomological inoculation rates to malaria transmission indices, Bayelsa State, Nigeria. AB - BACKGROUND & OBJECTIVES: Generally, indepth understanding of the epidemiology of malaria is considered a prerequisite for planning effective control measures in the endemic regions like sub-Saharan Africa. This study focuses on the relationship of entomological inoculation rates (EIRs) to malaria incidence and prevalence rates across eco-vegetational zones in Bayelsa State, Nigeria. METHODS: Mosquito sampling was undertaken in seven towns/villages in seven local government areas (LGAs) in three eco-vegetational zones. Adults were collected twice quarterly by the pyrethrum spray catch (PSC) technique. Anophelines were separated morphologically and the sibling species were identified using PCR. Detection of circumsporozoite (CS) antigen by ELISA was used for determining mosquito infection rates. Man-biting, sporozoite and entomological inoculation rates were calculated by standard methods. Simultaneously, malaria incidence and prevalence rates were calculated using data obtained from hospitals and by examination of blood smears from consenting adults. RESULTS: The estimated mean man-biting rate (MBR) over a 2-yr period was 6.88 bites/person/night. The highest MBR of 16.9 was in the mangrove coastal water forest and the least, 11.3, was in brackish water swamp forest; differences were significant (t = 12.083; p<0.05). The mean sporozoite rate of Anopheles gambiae sensu lato (s.l.) was 11%. The highest mean sporozoite rate was 13.4% for An. gambiae sensu stricto (s.s.), followed by 7.9% for An. arabiensis and the least was 0.4% for An. melas. Seasonal rates varied, highest for An. gambiae s.s. in the dry season, but highest for An. arabiensis in the wet season. The annual entomological inoculation rate of An. gambiae s.l. over a 2-yr period was 80.50 infective bites/person/year; the highest, 70.35 was in An. gambiae s.s. and the least, 0.15 in An. melas. When prevalence (PR), incidence (IR) and entomological inoculation (EIR) rates were incorporated in a logistic regression model, they showed 70.5 and 64% accuracy in predicting the relationship between EIR and, incidence and prevalence rates respectively. INTERPRETATION & CONCLUSION: Based on EIR values malaria transmission was classified as stable when EIR was >1.5 or unstable when EIR was <= 1.5. Although, earlier studies have shown correlation between EIRs and malaria PR, this study demonstrated a significant correlation between EIRs and malaria incidence rates. PMID- 27004580 TI - Performance evaluation of rapid diagnostic test for malaria in high malarious districts of Amhara region, Ethiopia. AB - BACKGROUND & OBJECTIVES: Malaria is one of the leading public health challenges in Ethiopia. To address this, the Federal Ministry of Ethiopia launched a laboratory diagnosis programme for promoting use of either rapid diagnostic tests (RDTs) or Giemsa microscopy to all suspected malaria cases. This study was conducted to assess the performance of RDT and influencing factors for Giemsa microscopic diagnosis in Amhara region. METHODS: A cross-sectional study was conducted in 10 high burden malaria districts of Amhara region from 15 May to 15 June 2014. Data were collected using structured questionnaire. Blood samples were collected from 1000 malaria suspected cases in 10 health centers. RDT (SD BIOLINE) and Giemsa microscopy were performed as per standard procedures. Kappa value, logistic regression and chi-square test were used for statistical analysis. RESULTS: The overall positivity rate (PR) of malaria parasites by RDT and Giemsa microscopy was 17.1 and 16.5% respectively. Compared to Giemsa microscopy as "gold standard", RDT showed 83.9% sensitivity and 96% specificity. The level of agreement between first reader and second reader for blood film microscopy was moderate (Kappa value = 0.74). Logistic regression showed that male, under five year of age and having fever more than 24 h prior to malaria diagnosis had statistically significant association with malaria positivity rate for malaria parasites. INTERPRETATION & CONCLUSION: The overall specificity and negative predictive values of RDT for malaria diagnosis were excellent. However, the sensitivity and positive predictive values of RDT were low. Therefore, in service training, quality monitoring of RDTs, and adequate laboratory supplies for diagnostic services of malaria would be crucial for effective intervention measures. PMID- 27004581 TI - Phlebotomine sandflies (Diptera: Psychodidae) in a sub-Andean forest from the Norte de Santander, Colombia. AB - BACKGROUND & OBJECTIVES: The recognition of communities of arthropods with medical importance in natural systems constitutes an important step in the prediction of possible epidemic events and/or emergence of infectious diseases in the human population. This is due to anthropogenic impact in natural areas and landscape modification, which changes the dynamics of pathogenic agents, reservoirs, and vector insects. In this study, an inventory was compiled of species of the genus Lutzomyia present in sub-Andean forest from the confluence of the Pamplonita River basin. METHODS: CDC-light and Shannon traps were used for collecting adult phlebotomine sandflies during the month of October 2013 in a sub Andean forest from river basin Pamplonita. All specimens were identified using morphological keys. The epidemiological relevance of each species was reported using a literature review about natural infection or vector incrimination with Leishmania species or other pathogens microorganism. RESULTS: A total of 2755 specimens belonging to eight species of the genus Lutzomyia were collected. Out of the eight species, seven belonged to the group verrucarum (Lutzomyia sp- townsendi series, L. ovallesi, L. spinicrassa, L. serrana, L. townsendi, L. nuneztovari and L. pia), while one belonged to the subgenus Helcocyrtomyia (L. hartmanni). A new registry of L. townsendi was observed for the Norte de Santander department. INTERPRETATION & CONCLUSION: The appreciable diversity of the verrucarum group observed in this area suggest further investigation on the biogeography and evolution of this group, and epidemiological risk for human populations around this area, as there are reports of Leishmania natural infection and favourable conditions for domestication of phlebotomines in rural towns. PMID- 27004582 TI - Molecular xenomonitoring of Wuchereria bancrofti in Culex quinquefasciatus from an endemic area: Comparison of two DNA extraction methods for realtime PCR assay. PMID- 27004583 TI - Antifolate resistance associated point mutations among asymptomatic malaria cases. PMID- 27004584 TI - Scrub typhus with longitudinally extensive transverse myelitis. PMID- 27004585 TI - A child with an unusual complication of Crimean-Congo hemorrhagic fever: Hemorrhagic pleural effusion. PMID- 27004586 TI - Subcutaneous filariasis in India--Possible indication of human Dirofilariasis. PMID- 27004587 TI - Author's Reply. PMID- 27004588 TI - Systematic review and meta-analysis of the diagnostic accuracy of ductoscopy in patients with pathological nipple discharge. AB - BACKGROUND: Invasive surgery remains the standard for diagnosis of pathological nipple discharge (PND). Only a minority of patients with nipple discharge and an unsuspicious finding on conventional breast imaging have cancer. Ductoscopy is a minimally invasive alternative for evaluation of PND. This systematic review and meta-analysis was designed to evaluate the diagnostic accuracy of ductoscopy in patients with PND. METHODS: A systematic search of electronic databases for studies addressing ductoscopy in patients with PND was conducted. Two classification systems were assessed. For DSany , all visualized ductoscopic abnormalities were classified as positive, whereas for DSsusp , only suspicious findings were considered positive. After checking heterogeneity, pooled sensitivity and specificity of DSany and DSsusp were calculated. RESULTS: The search yielded 4642 original citations, of which 20 studies were included in the review. Malignancy rates varied from 0 to 27 per cent. Twelve studies, including 1994 patients, were eligible for meta-analysis. Pooled sensitivity and specificity of DSany were 94 (95 per cent c.i. 88 to 97) per cent and 47 (44 to 49) per cent respectively. Pooled sensitivity and specificity of DSsusp were 50 (36 to 64) and 83 (81 to 86) per cent respectively. Heterogeneity between studies was moderate to large for sensitivity (DSany : I2 = 17.5 per cent; DSsusp : I2 = 37.9 per cent) and very large for specificity (DSany : I2 = 96.8 per cent; DSsusp : I2 = 92.6 per cent). CONCLUSION: Ductoscopy detects about 94 per cent of all underlying malignancies in patients with PND, but does not permit reliable discrimination between malignant and benign findings. PMID- 27004589 TI - The effect of pose variability and repeated reliability of segmental centres of mass acquisition when using 3D photonic scanning. AB - Three-dimensional (3D) photonic scanning is an emerging technique to acquire accurate body segment parameter data. This study established the repeated reliability of segmental centres of mass when using 3D photonic scanning (3DPS). Seventeen male participants were scanned twice by a 3D whole-body laser scanner. The same operators conducted the reconstruction and segmentation processes to obtain segmental meshes for calculating the segmental centres of mass. The segmental centres of mass obtained from repeated 3DPS were compared by relative technical error of measurement (TEM). Hypothesis tests were conducted to determine the size of change required for each segment to be determined a true variation. The relative TEMs for all segments were less than 5%. The relative changes in centres of mass at +/-1.5% for most segments can be detected (p < 0.05). The arm segments which are difficult to keep in the same scanning pose generated more error than other segments. Practitioner Summary: Three-dimensional photonic scanning is an emerging technique to acquire body segment parameter data. This study established the repeated reliability of segmental centres of mass when using 3D photonic scanning and emphasised that the error for arm segments need to be considered while using this technique to acquire centres of mass. PMID- 27004590 TI - Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain. AB - Chromosome 10q24.32-q24.33 is one of the most robustly supported risk loci to emerge from genome-wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele specific expression to assess cis-regulatory effects associated with the two best supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis-effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. (c) 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID- 27004591 TI - Colic in a working horse population in Egypt: Prevalence and risk factors. AB - REASONS FOR PERFORMING STUDY: Colic is an important health problem in managed horse populations. Currently, there is limited information about colic prevalence and risk factors for colic in working horse populations. OBJECTIVES: To determine the prevalence of, and risk factors for, colic in a working horse population in Egypt and to describe management practices in this working horse population. STUDY DESIGN: Cross-sectional survey. METHODS: Owners of 350 working horses were interviewed. Data about their horses, management and colic episodes in the preceding 12 months were collected. Dental examination was conducted on 342 horses and blood samples (n = 100) were collected for immunodiagnosis of tapeworm (Anoplocephala perfoliata) infection. Multivariable logistic regression analysis was used to identify risk factors for a history of colic in the preceding 12 months. RESULTS: The 12-month prevalence of colic was 54.6%. Severe and moderate tapeworm infection intensity was identified in 3% and 26% of horses tested, respectively. Horses that had severe dental disease (odds ratio [OR] 6.8, 95% confidence interval [CI] 1.9-24.3, P<0.001), that displayed stereotypic behaviour (OR 2.0, 95% CI 1.15-3.5, P = 0.013), were fed ground corn during the 'dry season' (OR 1.65, 95% CI 1.03-2.6, P = 0.035) or that had received an anthelmintic in the previous 6 months (OR 2.1, 95% CI 1.3-3.3, P = 0.003) were more likely to have a history of colic in the preceding 12 months. Horses fed on rice bran during the 'green season' (OR 0.47, 95% CI 0.26-0.9, P = 0.015) and that displayed geophagia/coprophagia (OR 0.19, 95% CI 0.05-0.73, P = 0.001) were less likely to have a history of colic. CONCLUSIONS: Colic is common in this working horse population and this study has identified factors associated with altered likelihood of colic. The study provides important information that may be used to inform future prospective studies investigating colic in working horse populations and to assist development of preventive healthcare strategies. The Summary is available in Chinese - see Supporting information. PMID- 27004592 TI - Palladium-Catalyzed Benzylic Arylation of Pyridylmethyl Silyl Ethers: One-Pot Synthesis of Aryl(pyridyl)methanols. AB - An efficient palladium-catalyzed direct arylation of pyridylmethyl silyl ethers with aryl bromides is described. A Pd(OAc)2/NIXANTPHOS-based catalyst provides aryl(pyridyl)methyl alcohol derivatives in good to excellent yields (33 examples, 57-100% yield). This protocol is compatible with different silyl ether protecting groups, affording either the protected or the free alcohols in an effective one pot process. The scalability of the reaction is demonstrated. PMID- 27004593 TI - The policy and practices of New South Wales drug treatment providers in responding to the possession of illicit substances on premises. AB - INTRODUCTION AND AIMS: Responding to possession of illicit substances on the premises of drug treatment services is a complex issue. Providers are challenged by balancing duty-of-care and staff safety while attempting to provide a therapeutic environment. This study assessed the current policy and practice of non-government drug treatment services in New South Wales, Australia in responding to possession of illicit substances on their premises. DESIGN AND METHODS: Non-government drug treatment services were invited to participate in a survey that aimed to elicit information about existing policy and practices and how often it occurred. Analysis explored the differences between services that had a written policy and those that did not against service setting, accreditation status, reporting of an illicit drug possession in the last 12 months and having a sharps disposal unit. RESULTS: Fifty-one responses were included in the analysis, 29 (57%) of which reported having a policy and/or procedure. There was no statistically discernible difference between inpatient and outpatient settings, accreditation status of services or availability of a sharps disposal unit on the premises. However, services that reported a possession incident in the previous 12 months were more likely to report having a written policy than those that did not (37% vs. 12%; odds ratio: 4.75, 95% confidence interval 1.32-17.11, P = 0.014). DISCUSSION AND CONCLUSIONS: The policy and practice in these settings vary greatly, with many services reporting no documented policy to guide staff. The findings suggest the need to develop organisational policy to support service providers in responding to possession of illicit substances on premises. [Stirling R, Day C. The policy and practices of New South Wales drug treatment providers in responding to the possession of illicit substances on premises. Drug Alcohol Rev 2016;35:644-649]. PMID- 27004594 TI - Differences in caregiver daily impression by sex, education and career length. AB - AIM: We previously proposed the concept of caregiver daily impression (CDI) as a practical tool for emergency triage. We herein assessed how CDI varies by sex, education and career length by determining CDI scores as quantitative outcome measures. METHODS: We carried out a cross-sectional study using a self-reported questionnaire among caregivers in 20 long-term care facilities in Hyogo, Japan. A total of 10 CDI variables measured participants' previous experience of emergency transfers using a scale from 0-10. The resulting total was defined as the CDI score. We hypothetically considered that higher scores indicated greater caregiver focus. The CDI scores were compared by sex, education and career length using analysis of covariance. RESULTS: A total of 601 personal caregivers were evaluated (mean age 36.7 years; 36% men). The mean career length was 6.9 years, with the following groupings: 1-4 years (38%), 5-9 years (37%) and >10 years (24%). After adjustment for sex and education, the CDI scores for the variable, "poor eye contact," significantly differed between caregivers with >=10 and <5 years of experience (scores of 5.0 +/- 3.1 and 4.0 +/- 2.7, respectively). The CDI scores for variables related to eyes tended to increase with experience, whereas other CDI scores decreased. Male caregivers focused on residents' eyes significantly more than did female caregivers. CONCLUSIONS: We found that the CDI variable, "poor eye contact," is influenced by career length. Caregivers with more experience attach more importance to their impression of residents' eyes than do those with less experience. Sex-related differences in CDI might also exist. Geriatr Gerontol Int 2016; 17: 410-415. PMID- 27004596 TI - Memory rehabilitation for people with multiple sclerosis. AB - BACKGROUND: This is an update of the Cochrane review 'Memory rehabilitation for people with multiple sclerosis' (first published in the Cochrane Library 14 March 2012, Issue 3). Impairments in cognitive function, particularly memory, are common in people with multiple sclerosis (MS) and can potentially affect their ability to complete functional activities. There is evidence from single-case or small group studies that memory rehabilitation can be beneficial for people with MS, but findings from randomised controlled trials (RCTs) and systematic reviews have been inconclusive. OBJECTIVES: To determine whether people with MS who received memory rehabilitation showed: 1. better outcomes in their memory functions compared to those given no treatment or receiving a placebo control; and 2. better functional abilities, in terms of activities of daily living, mood, and quality of life, than those who received no treatment or a placebo. SEARCH METHODS: We searched the Trials Specialised Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (2 June 2015) and the following electronic databases: The NIHR Clinical Research Network Portfolio database (NIHR CRN) (from 2010 to June 2015), The Allied and Complementary Medicine Database (AMED) (2010 to June 2015), British Nursing Index (BNI) (2010 to June 2015), PsycINFO (2011 to June 2015), and CAB Abstracts (2010 to June 2015). Start dates for the electronic databases coincided with the last search for the previous review. We handsearched relevant journals and reference lists. SELECTION CRITERIA: We selected RCTs or quasi-randomised trials of memory rehabilitation or cognitive rehabilitation for people with MS in which a memory rehabilitation treatment group was compared to a control group. Selection was conducted independently first and then confirmed through group discussion. We excluded studies that included participants whose memory deficits were the result of conditions other than MS unless we could identify a subgroup of participants with MS with separate results. DATA COLLECTION AND ANALYSIS: Three review authors were involved in this update in terms of study selection, quality assessment, and data extraction. We contacted investigators of primary studies for further information where required. We conducted data analysis and synthesis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We performed a 'best evidence' synthesis based on the methodological quality of the primary studies included. MAIN RESULTS: We added seven studies during this update, bringing the total to 15 studies, involving 989 participants. The interventions involved various memory retraining techniques, such as computerised programmes and training on internal and external memory aids. Control groups varied in format from assessment-only groups, discussion and games, non-specific cognitive retraining, and attention or visuospatial training. The risk of bias of the included studies was generally low, but we found eight studies to have high risk of bias related to certain aspects of their methodology.We found significant effect of intervention on objective assessments of memory in both the immediate and long-term follow-ups: standardised mean difference (SMD) 0.23 (95% confidence interval (CI) 0.05 to 0.41) and SMD 0.26 (95% CI 0.03 to 0.49), respectively. We also found significant effect of intervention for quality of life in the immediate follow-up (SMD 0.23 (95% CI 0.05 to 0.41)). These findings showed that the intervention group performed significantly better than the control group. We also found a significant difference for activities of daily living (ADL) in the long-term follow-up (SMD -0.33 (95% CI -0.63 to -0.03)), showing that the control groups had significantly less difficulty completing ADLs than the intervention groups. We found no significant effects, either immediate or long-term, on subjective reports of memory problems (SMD 0.04 (95% CI -0.19 to 0.27) and SMD 0.04 (95% CI -0.19 to 0.27)); on mood (SMD 0.02 (95% CI -0.16 to 0.20) and SMD 0.01 (95% CI -0.21 to 0.20)); and on immediate follow-up for ADL (SMD -0.13 (95% CI -0.60 to 0.33)) and in the long term for quality of life (SMD 0.16 (95% CI 0.03 to 0.36)). We could not complete a sensitivity analysis of intention-to treat in comparison with per-protocol analysis, due to insufficient information from the included papers. However, a sensitivity analysis of high- versus low risk studies suggested that while quality of the trials did not affect most outcomes, differences were seen in the objective memory outcomes (both at immediate and long term) and quality of life (immediate) outcome, with studies with higher risk of bias inflating the overall effect size estimates for these outcomes, and the test of overall effect changing from being statistically significant to not significant when studies at high risk of bias were excluded. This suggests that lower-quality studies may have positively influenced the outcomes. AUTHORS' CONCLUSIONS: There is some evidence to support the effectiveness of memory rehabilitation on memory function, as well as on quality of life. However, the evidence is limited and does not extend to subjective reports of memory functioning or mood. Furthermore, the objective measures used are not ecologically valid measures, and thus potentially limit generalisability of these findings into daily life. Further robust RCTs of high methodological quality and better quality of reporting, using ecologically valid outcome assessments, are still needed. PMID- 27004595 TI - Human papillomavirus mRNA and DNA testing in women with atypical squamous cells of undetermined significance: A prospective cohort study. AB - In this prospective cohort study, we compared the performance of human papillomavirus (HPV) mRNA and DNA testing of women with atypical squamous cells of undetermined significance (ASC-US) during cervical cancer screening. Using a nationwide Danish pathology register, we identified women aged 30-65 years with ASC-US during 2005-2011 who were tested for HPV16/18/31/33/45 mRNA using PreTect HPV-Proofer (n = 3,226) or for high-risk HPV (hrHPV) DNA using Hybrid Capture 2 (HC2) (n = 9,405) or Linear Array HPV-Genotyping test (LA) (n = 1,533). Women with >=1 subsequent examination in the register (n = 13,729) were followed for up to 9.5 years for high-grade cervical intraepithelial neoplasia (CIN) or cancer. After 3 years' follow-up, mRNA testing had higher specificity for CIN3 or worse (CIN3+) than HC2 testing (88.1% [95% confidence interval (CI): 86.8-89.6%] versus 59.3% [95% CI: 58.1-60.4%]) and higher positive predictive value (PPV) (38.2% [95% CI: 33.8%-43.1%] versus 19.5% [95% CI: 17.8-20.9%]). However, the sensitivity of mRNA testing was lower than that of HC2 testing (66.7% [95% CI: 59.3-74.5%] versus 97.0% [95% CI: 95.5-98.4%]), and women testing mRNA negative had higher 3-year risk for CIN3+ than those testing HC2 negative (3.2% [95% CI: 2.2-4.2%] versus 0.5% [95% CI: 0.3-0.7%]). Patterns were similar after 18 months and 5 years'; follow-up; for CIN2+ and cancer as outcomes; across all age groups; and when comparing mRNA testing to hrHPV DNA testing using LA. In conclusion, the HPV16/18/31/33/45 mRNA test is not optimal for ASC-US triage due to its low sensitivity and the substantial risk for precancer following a negative test. PMID- 27004597 TI - Reduced DNA methylation patterning and transcriptional connectivity define human skin aging. AB - Epigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age-related changes in DNA methylation at the genome scale have been termed 'epigenetic drift', but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age-related epigenetic changes because of its substantial cell-type homogeneity and its well-known age-related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N = 108) using array-based profiling of 450 000 methylation marks in various age groups. Data analysis confirmed that age-related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovered an age-related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome. PMID- 27004598 TI - Effect of rs1063843 in the CAMKK2 gene on the dorsolateral prefrontal cortex. AB - Recently, a single nucleotide polymorphism (SNP) in the CAMKK2 gene (rs1063843) was found to be associated with lower expression of the gene in the dorsolateral prefrontal cortex (DLPFC) and with schizophrenia (SCZ) and deficits in working memory and executive function. However, the brain mechanism underlying this association is poorly understood. A functional magnetic resonance imaging (fMRI) study (N = 84 healthy volunteers) involving multiple cognitive tasks, including a Stroop task (to measure attentional executive control), an N-back task (to measure working memory), and a delay discounting task (to measure decision making) to identify the brain regions affected by rs1063843 was performed. Across all three tasks, it was found that carriers of the risk allele consistently exhibited increased activation of the left DLPFC. In addition, the risk allele carriers also exhibited increased activation of the right DLPFC and the left cerebellum during the Stroop task and of the left caudate nucleus during the N back task. These findings helped to elucidate the role of CAMKK2 in cognitive functions and in the etiology of SCZ. Hum Brain Mapp 37:2398-2406, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004599 TI - Neuroanatomical variation in autism spectrum disorder: A comprehensive review. AB - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in socialization, communication, and behavior. Many investigators have described the anatomical abnormalities in autistic brains, in an attempt to correlate them with the manifestations of ASD. Herein, we reviewed all the available literature about the neuroanatomical findings in ASD available via "PubMed" and "Google Scholar." References found in review articles were also searched manually. There was substantial discrepancy throughout the literature regarding the reported presence and significance of neuroanatomical findings in ASD, and this is thoroughly discussed in the present review. PMID- 27004600 TI - Functional specialization of one copy of glutamine phosphoribosyl pyrophosphate amidotransferase in ureide production from symbiotically fixed nitrogen in Phaseolus vulgaris. AB - Purines are essential molecules formed in a highly regulated pathway in all organisms. In tropical legumes, the nitrogen fixed in the nodules is used to generate ureides through the oxidation of de novo synthesized purines. Glutamine phosphoribosyl pyrophosphate amidotransferase (PRAT) catalyses the first committed step of de novo purine synthesis. In Phaseolus vulgaris there are three genes coding for PRAT. The three full-length sequences, which are intron-less genes, were cloned, and their expression levels were determined under conditions that affect the synthesis of purines. One of the three genes, PvPRAT3, is highly expressed in nodules and protein amount and enzymatic activity in these tissues correlate with nitrogen fixation activity. Inhibition of PvPRAT3 gene expression by RNAi-silencing and subsequent metabolomic analysis of the transformed roots shows that PvPRAT3 is essential for the synthesis of ureides in P. vulgaris nodules. PMID- 27004601 TI - The importance of surgical margins in prostate cancer. AB - Positive surgical margins (PSM) after radical prostatectomy (RP) are a predictor of biochemical recurrence (BCR), and highly dependent on surgeon, experience, and skill. The length and location PSMs are important, with significant differences between open and robotic RP. The impact of PSMs on BCR remains secondary to other clinico-pathologic variables: Gleason Score, pathologic stage, and baseline PSA. However, lower PSM rates are associated with reduced use of secondary interventions and patient anxiety of cancer recurrence. PMID- 27004602 TI - Electrochemical synthesis of poly(3-aminophenylboronic acid) in ethylene glycol without exogenous protons. AB - A non-aqueous solution of tetra-n-butylammonium fluoride (TBAF) in ethylene glycol has been tried for the first time as a supporting electrolyte for the electropolymerization of 3-aminophenylboronic acid (APBA). Unlike the traditional acidic aqueous solution, the present medium needs no exogenous protons; moreover, the presence of CF3COOH is found to be unfavorable for the polymerization. The protons are in situ generated by the reaction between the boronic acid group on APBA and 1,2-dihydroxyl on ethylene glycol. So, ethylene glycol serves as not only the solvent but also the proton source. As a part of the supporting electrolyte, F(-) is found to be involved in the electrochemical synthesis of poly(3-aminophenylboronic acid) (PAPBA), but it is not indispensable. Studies on the electropolymerization process indicate that the size of the ions in the electrolyte affects the rate of the doping/dedoping process. The smaller the cation, the easier the doping/dedoping process, and the better the stability of the grown film. As demonstrated by Fourier transform infrared spectra, UV-vis spectra, and scanning electron microscopy, the obtained PAPBA is a cross-linked nanoporous polymer membrane that has a good adherence to the glassy carbon electrode. PMID- 27004604 TI - Monitoring the intracellular calcium response to a dynamic hypertonic environment. AB - The profiling of physiological response of cells to external stimuli at the single cell level is of importance. Traditional approaches to study cell responses are often limited by ensemble measurement, which is challenging to reveal the complex single cell behaviors under a dynamic environment. Here we report the development of a simple microfluidic device to investigate intracellular calcium response to dynamic hypertonic conditions at the single cell level in real-time. Interestingly, a dramatic elevation in the intracellular calcium signaling is found in both suspension cells (human leukemic cell line, HL 60) and adherent cells (lung cancer cell line, A549), which is ascribed to the exposure of cells to the hydrodynamic stress. We also demonstrate that the calcium response exhibits distinct single cell heterogeneity as well as cell-type dependent responses to the same stimuli. Our study opens up a new tool for tracking cellular activity at the single cell level in real time for high throughput drug screening. PMID- 27004603 TI - Single-cell mass spectrometry with multi-solvent extraction identifies metabolic differences between left and right blastomeres in the 8-cell frog (Xenopus) embryo. AB - Single-cell metabolic mass spectrometry enables the discovery (untargeted) analysis of small molecules in individual cells. Using single-cell capillary electrophoresis high-resolution mass spectrometry (CE-HRMS), we recently uncovered small-molecule differences between embryonic cells located along the animal-vegetal and dorsal-ventral axes of the 16-cell frog (Xenopus laevis) embryo, raising the question whether metabolic cell heterogeneity also exists along the left-right body axis. To address this question, we here advance single cell CE-HRMS for identifying and quantifying metabolites in higher analytical sensitivity, and then use the methodology to compare metabolite production between left and right cells. Our strategy utilizes multiple solvents with complementary physicochemical properties to extract small molecules from single cells and improve electrophoretic separation, increasing metabolite ion signals for quantification and tandem HRMS. As a result, we were able to identify 55 different small molecules in D1 cells that were isolated from 8-cell embryos. To quantify metabolite production between left and right cells, we analyzed n = 24 different D1 cells in technical duplicate-triplicate measurements. Statistical and multivariate analysis based on 80 of the most repeatedly quantified compounds revealed 10 distinct metabolites that were significantly differentially accumulated in the left or right cells (p < 0.05 and fold change >=1.5). These metabolites were enriched in the arginine-proline metabolic pathway in the right, but not the left D1 cells. Besides providing analytical benefits for single-cell HRMS, this work provides new metabolic data on the establishment of normal body asymmetry in the early developing embryo. PMID- 27004606 TI - Irradiation deformation near different atomic grain boundaries in alpha-Zr: An investigation of thermodynamics and kinetics of point defects. AB - Understanding radiation performance of nanocrystalline Zr-based alloys is essential to develop internal components and external cladding materials with self-healing capabilities for longer and safer life cycles in harsh reactor environments. However, the precise role of interfaces in modifying defect production and evolution in alpha-Zr is not yet determined. Using atomistic simulation methods, we investigate the influence of different atomic grain boundaries (GBs) in thermodynamic and kinetic properties of defects on short timescales. We observe that the sink efficiency and sink strength of interfaces vary significantly with the boundary structures, with a preference to absorb interstitials (vacancies) when the GBs are semi-parallel (semi-perpendicular) relative to the basal planes. Further, we identify three distinct primary cascade geometries, and find that the residual defect clustering in grain interiors depends on how the atomic GBs modify the spatial distribution of defects within the crystal structure. Finally, we explain and discuss the dynamic results in terms of energetic and kinetic behaviors of defects near the pristine and damaged boundaries. Eventually, these will provide a microscopic reference for further improving the radiation response of Zr by using fine grains or by introducing a high density of dispersoids in material metallurgy. PMID- 27004605 TI - Leaders should not be conformists in evolutionary social dilemmas. AB - The most common assumption in evolutionary game theory is that players should adopt a strategy that warrants the highest payoff. However, recent studies indicate that the spatial selection for cooperation is enhanced if an appropriate fraction of the population chooses the most common rather than the most profitable strategy within the interaction range. Such conformity might be due to herding instincts or crowd behavior in humans and social animals. In a heterogeneous population where individuals differ in their degree, collective influence, or other traits, an unanswered question remains who should conform. Selecting conformists randomly is the simplest choice, but it is neither a realistic nor the optimal one. We show that, regardless of the source of heterogeneity and game parametrization, socially the most favorable outcomes emerge if the masses conform. On the other hand, forcing leaders to conform significantly hinders the constructive interplay between heterogeneity and coordination, leading to evolutionary outcomes that are worse still than if conformists were chosen randomly. We conclude that leaders must be able to create a following for network reciprocity to be optimally augmented by conformity. In the opposite case, when leaders are castrated and made to follow, the failure of coordination impairs the evolution of cooperation. PMID- 27004608 TI - A Flexible and Wearable Human Stress Monitoring Patch. AB - A human stress monitoring patch integrates three sensors of skin temperature, skin conductance, and pulsewave in the size of stamp (25 mm * 15 mm * 72 MUm) in order to enhance wearing comfort with small skin contact area and high flexibility. The skin contact area is minimized through the invention of an integrated multi-layer structure and the associated microfabrication process; thus being reduced to 1/125 of that of the conventional single-layer multiple sensors. The patch flexibility is increased mainly by the development of flexible pulsewave sensor, made of a flexible piezoelectric membrane supported by a perforated polyimide membrane. In the human physiological range, the fabricated stress patch measures skin temperature with the sensitivity of 0.31 Omega/ degrees C, skin conductance with the sensitivity of 0.28 MUV/0.02 MUS, and pulse wave with the response time of 70 msec. The skin-attachable stress patch, capable to detect multimodal bio-signals, shows potential for application to wearable emotion monitoring. PMID- 27004607 TI - Illuminating drug action by network integration of disease genes: a case study of myocardial infarction. AB - Drug discovery has produced many successful therapeutic agents; however, most of these drugs were developed without a deep understanding of the system-wide mechanisms of action responsible for their indications. Gene-disease associations produced by molecular and genetic studies of complex diseases provide great opportunities for a system-level understanding of drug activity. In this study, we focused on acute myocardial infarction (MI) and conducted an integrative network analysis to illuminate drug actions. We integrated MI drugs, MI drug interactors, drug targets, and MI disease genes into the human interactome and showed that MI drug targets are significantly proximate to MI disease proteins. We then constructed a bipartite network of MI-related drug targets and MI disease proteins and derived 12 drug-target-disease (DTD) modules. We assessed the biological relevance of these modules and demonstrated the benefits of incorporating disease genes. The results indicate that DTD modules provide insights into the mechanisms of action of MI drugs and the cardiovascular (side) effects of non-MI drugs. PMID- 27004609 TI - Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity. AB - Maternal obesity is associated with an increased risk of chronic disease in offspring, including type 2 diabetes (T2D). Exendin-4 (Exd-4) activates the glucagon like peptide-1 (GLP-1) receptor thereby decreasing serum glucose levels and body weight. In addition, Exd-4 has been shown to reduce renal and cardiac complications in experimental models of T2D. We hypothesized that treatment with Exd-4 would ameliorate the detrimental effects of maternal and diet-induced obesity on renal characteristics in offspring. Female Sprague-Dawley rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation, and their offspring were weaned to normal or HFD. The offspring were randomized to Exd-4 or placebo from weaning and their kidneys harvested at Week 9. We found that the kidneys of offspring from obese mothers, regardless of postnatal diet, had significantly increased markers of inflammation, oxidative stress and fibrosis. Exd-4 ameliorated the negative renal effects of maternal obesity and in particular, reduced renal inflammation, oxidative stress and fibrosis. In conclusion, maternal obesity has persisting effects on renal structure in the offspring. GLP-1 analogues are potentially useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring. PMID- 27004610 TI - Long-term increase in snow depth leads to compositional changes in arctic ectomycorrhizal fungal communities. AB - Many arctic ecological processes are regulated by soil temperature that is tightly interconnected with snow cover distribution and persistence. Recently, various climate-induced changes have been observed in arctic tundra ecosystems, e.g. shrub expansion, resulting in reduction in albedo and greater C fixation in aboveground vegetation as well as increased rates of soil C mobilization by microbes. Importantly, the net effects of these shifts are unknown, in part because our understanding of belowground processes is limited. Here, we focus on the effects of increased snow depth, and as a consequence, increased winter soil temperature on ectomycorrhizal (ECM) fungal communities in dry and moist tundra. We analyzed deep DNA sequence data from soil samples taken at a long-term snow fence experiment in Northern Alaska. Our results indicate that, in contrast with previously observed responses of plants to increased snow depth at the same experimental site, the ECM fungal community of the dry tundra was more affected by deeper snow than the moist tundra community. In the dry tundra, both community richness and composition were significantly altered while in the moist tundra, only community composition changed significantly while richness did not. We observed a decrease in richness of Tomentella, Inocybe and other taxa adapted to scavenge the soil for labile N forms. On the other hand, richness of Cortinarius, and species with the ability to scavenge the soil for recalcitrant N forms, did not change. We further link ECM fungal traits with C soil pools. If future warmer atmospheric conditions lead to greater winter snow fall, changes in the ECM fungal community will likely influence C emissions and C fixation through altering N plant availability, fungal biomass and soil-plant C-N dynamics, ultimately determining important future interactions between the tundra biosphere and atmosphere. PMID- 27004611 TI - Non-adiabatic excited state molecular dynamics of phenylene ethynylene dendrimer using a multiconfigurational Ehrenfest approach. AB - Photoinduced dynamics of electronic and vibrational unidirectional energy transfer between meta-linked building blocks in a phenylene ethynylene dendrimer is simulated using a multiconfigurational Ehrenfest in time-dependent diabatic basis (MCE-TDDB) method, a new variant of the MCE approach developed by us for dynamics involving multiple electronic states with numerous abrupt crossings. Excited-state energies, gradients and non-adiabatic coupling terms needed for dynamics simulation are calculated on-the-fly using the Collective Electron Oscillator (CEO) approach. A comparative analysis of our results obtained using MCE-TDDB, the conventional Ehrenfest method and the surface-hopping approach with and without decoherence corrections is presented. PMID- 27004612 TI - Immunogenicity of a Trivalent Recombinant Vaccine Against Clostridium perfringens Alpha, Beta, and Epsilon Toxins in Farm Ruminants. AB - Clostridium perfringens is an anaerobic bacterium that produces several toxins. Of these, the alpha, beta, and epsilon toxins are responsible for causing the most severe C. perfringens-related diseases in farm animals. The best way to control these diseases is through vaccination. However, commercially available vaccines are based on inactivated toxins and have many production drawbacks, which can be overcome through the use of recombinant antigens. In this study, we produced recombinant alpha, beta, and epsilon toxins in Escherichia coli to formulate a trivalent vaccine. Its effectiveness was evaluated through a potency test in rabbits, in which the vaccine generated 9.6, 24.4, and 25.0 IU/mL of neutralizing antibodies against the respective toxins. Following this, cattle, sheep, and goats received the same formulation, generating, respectively, 5.19 +/ 0.48, 4.34 +/- 0.43, and 4.70 +/- 0.58 IU/mL against alpha toxin, 13.71 +/- 1.17 IU/mL (for all three species) against beta toxin, and 12.74 +/- 1.70, 7.66 +/- 1.69, and 8.91 +/- 2.14 IU/mL against epsilon toxin. These levels were above the minimum recommended by international protocols. As such, our vaccine was effective in generating protective antibodies and, thus, may represent an interesting alternative for the prevention of C. perfringens-related intoxications in farm animals. PMID- 27004613 TI - PolyGuanine methacrylate cryogels for ribonucleic acid purification. AB - The isolation and purification of ribonucleic acid have attracted attention recently for the understanding of the functions in detail because of the necessity for the treatment of genetic diseases. In this study, guanine incorporated polymeric cryogels were developed to obtain highly purified ribonucleic acid. The satisfactory purification performance was achieved with the guanine-incorporated poly (2-hydroxyethyl methacrylate-guanine methacrylate) cryogels. The most crucial advantages to use guanine as a functional monomer are to obtain a real natural interaction between guanine on the polymeric material and cytosine on the ribonucleic acid. Moreover, using cryogel with a highly porous structure and high swelling ratio provide advantages of getting more water within the structure to get more analyte to interact. The characterization of cryogels has proved the success of the synthesis and the perfect natural interaction to be taken place between the ligand (guanine methacrylate) and the cytosine in the ribonucleic acid molecules. Although the pores within the structure of cryogels are small, they provide efficient and fast adsorption. The chromatographic separation performance was investigated for different conditions (pH, temperature etc.). The desorption ratio and reusability were also analyzed at the end of the five adsorption-desorption cycles with no significant changes. PMID- 27004614 TI - Atomically ordered solute segregation behaviour in an oxide grain boundary. AB - Grain boundary segregation is a critical issue in materials science because it determines the properties of individual grain boundaries and thus governs the macroscopic properties of materials. Recent progress in electron microscopy has greatly improved our understanding of grain boundary segregation phenomena down to atomistic dimensions, but solute segregation is still extremely challenging to experimentally identify at the atomic scale. Here, we report direct observations of atomic-scale yttrium solute segregation behaviours in an yttria-stabilized zirconia grain boundary using atomic-resolution energy-dispersive X-ray spectroscopy analysis. We found that yttrium solute atoms preferentially segregate to specific atomic sites at the core of the grain boundary, forming a unique chemically-ordered structure across the grain boundary. PMID- 27004615 TI - Plant nuclear proteomics for unraveling physiological function. AB - The nucleus is the subcellular organelle that functions as the regulatory hub of the cell and is responsible for regulating several critical cellular functions, including cell proliferation, gene expression, and cell survival. Nuclear proteomics is a useful approach for investigating the mechanisms underlying plant responses to abiotic stresses, including protein-protein interactions, enzyme activities, and post-translational modifications. Among abiotic stresses, flooding is a major limiting factor for plant growth and yields, particularly for soybean. In this review, plant nuclei purification methods, modifications of plant nuclear proteins, and recent contributions to the field of plant nuclear proteomics are summarized. In addition, to reveal the upstream regulating mechanisms controlling soybean responses to flooding stress, the functions of flooding-responsive nuclear proteins are reviewed based on the results of nuclear proteomic analysis of soybean in the early stages of flooding stress. PMID- 27004616 TI - Expansion of phenotype and genotypic data in CRB2-related syndrome. AB - Sequence variants in CRB2 cause a syndrome with greatly elevated maternal serum alpha-fetoprotein and amniotic fluid alpha-fetoprotein levels, cerebral ventriculomegaly and renal findings similar to Finnish congenital nephrosis. All reported patients have been homozygotes or compound heterozygotes for sequence variants in the Crumbs, Drosophila, Homolog of, 2 (CRB2) genes. Variants affecting CRB2 function have also been identified in four families with steroid resistant nephrotic syndrome, but without any other known systemic findings. We ascertained five, previously unreported individuals with biallelic variants in CRB2 that were predicted to affect function. We compiled the clinical features of reported cases and reviewed available literature for cases with features suggestive of CRB2-related syndrome in order to better understand the phenotypic and genotypic manifestations. Phenotypic analyses showed that ventriculomegaly was a common clinical manifestation (9/11 confirmed cases), in contrast to the original reports, in which patients were ascertained due to renal disease. Two children had minor eye findings and one was diagnosed with a B-cell lymphoma. Further genetic analysis identified one family with two affected siblings who were both heterozygous for a variant in NPHS2 predicted to affect function and separate families with sequence variants in NPHS4 and BBS7 in addition to the CRB2 variants. Our report expands the clinical phenotype of CRB2-related syndrome and establishes ventriculomegaly and hydrocephalus as frequent manifestations. We found additional sequence variants in genes involved in kidney development and ciliopathies in patients with CRB2-related syndrome, suggesting that these variants may modify the phenotype. PMID- 27004618 TI - A novel feature extraction for robust EMG pattern recognition. AB - This paper presents the detailed evaluation and classification of Surface Electromyogram (SEMG) signals at different upper arm muscles for different operations. After acquiring the data from selected locations, interpretation of signals was done for the estimation of parameters using simulated algorithm. First, different types of arm operations were analysed; then statistical techniques were implemented for investigating muscle force relationships in terms of amplitude estimation. The classification (Artificial Neural Network) based results have been presented for detecting different pre-defined arm motions in order to discriminate SEMG signals. The outcome of research indicates that a neural network classifier performs best with an average classification rate of 92.50%. Finally, the result also inferred the operations which were observed to be easy for arm recognition and the study is a step forward to develop powerful, flexible and efficient prosthetic designs. PMID- 27004617 TI - Increasing fruit and vegetable intake has no effect on retinal vessel caliber in adults at high risk of developing cardiovascular disease. AB - BACKGROUND AND AIM: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk. METHODS AND RESULTS: Following a 4 week washout period, participants were randomized to consume either 2 or 4 or 7 portions of FV daily for 12 weeks. Retinal vessel caliber was measured at baseline and post-intervention. A total of 62 participants completed the study. Self-reported FV intake indicated good compliance with the intervention, with serum concentrations of zeaxanthin and lutein increasing significantly across the groups in a dose-dependent manner (P for trend < 0.05). There were no significant changes in body composition, 24-h ambulatory blood pressure or fasting blood lipid profiles in response to the FV intervention. Increasing age was a significant determinant of wider retinal venules (P = 0.004) whereas baseline systolic blood pressure was a significant determinant of narrower retinal arterioles (P = 0.03). Overall, there was no evidence of any short-term dose response effect of FV intake on retinal vessel caliber (CRAE (P = 0.92) or CRVE (P = 0.42)). CONCLUSIONS: This study demonstrated no effect of increasing FV intake on retinal vessel caliber in overweight adults at high risk of developing primary CVD. CLINICAL TRIAL REGISTRATION: NCT00874341. PMID- 27004620 TI - Cutaneous larva migrans, welcome to a warmer Europe. PMID- 27004619 TI - Outcome of patients with nonmetastatic muscle-invasive bladder cancer not undergoing cystectomy after treatment with noncisplatin-based chemotherapy and/or radiotherapy: a retrospective analysis. AB - Transurethral resection of bladder tumor (TURBT), radiotherapy, chemotherapy, or combinations can be used in patients with muscle-invasive bladder cancer (MIBC) not undergoing cystectomy. Nevertheless, unfitness for cystectomy is frequently associated with unfitness for other therapeutic modalities. We report the outcome of patients with MIBC who did not undergo cystectomy and did not receive cisplatin-based chemotherapy. Selection criteria for the study were nonmetastatic MIBC, no cystectomy, no cisplatin-based chemotherapy. Chemotherapy and/or radiotherapy should have been used aside from TURBT. Forty-nine patients (median age 79), managed between April 2001 and January 2012, were included in this analysis. Median Charlson Comorbidity Index was 5, while 76% were unfit for cisplatin. Treatment included radiotherapy (n = 7), carboplatin-based chemotherapy (n = 25), carboplatin-based chemotherapy followed by radiotherapy (n = 10), and radiochemotherapy (n = 7). Five-year event-free rate was 26% (standard error [SE] = 7) for overall survival, 23% (SE = 7) for progression-free survival, and 30 (SE = 8) for cancer-specific survival (CSS). Patients who were treated with combination of radiotherapy and chemotherapy had significantly longer CSS compared to those treated with radiotherapy or chemotherapy only (5-year CSS rate: 16% [SE 8] vs. 63% [SE 15], P = 0.053). Unfit-for-cystectomy patients frequently receive suboptimal nonsurgical treatment. Their outcome was poor. Combining chemotherapy with radiotherapy produced better outcomes and should be prospectively evaluated. PMID- 27004621 TI - Fenethylline (Captagon) Abuse - Local Problems from an Old Drug Become Universal. AB - Fenethylline is a theophylline derivative of amphetamine having stimulant effects similar to those of other amphetamine-type derivatives. Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of 'captagon'. Unlike other drugs of abuse, the clandestine synthesis of fenethylline is simple, using inexpensive laboratory instrumentation and raw materials legal to obtain. A review of all the existing knowledge of fenethylline is reported, concerning its chemistry, synthesis, pharmacology and toxicology, legislation, its prevalence and use as drug of abuse, as well as its analysis in biological or seized samples. Published or reported captagon-related cases and seizures are also presented. All the reviewed information was gathered through a detailed search of PubMed and the Internet. The primary drug market for fenethylline (as captagon) has traditionally been countries located on the Arabian Peninsula but also North Africa since 2013. In Arab countries, millions of captagon tablets are seized every year which represents one-third of global amphetamines seizures within a year. Furthermore, three of four patients treated for drug problems in Saudi Arabia are addicted to amphetamines, almost exclusively in the form of captagon. Significant information on fenethylline is provided for pharmacologists, toxicologists and forensic pathologists. Fenethylline, although old, has recently been introduced to the drug market, especially in Arab countries. Continuous community alertness is needed to tackle this current growing phenomenon. PMID- 27004622 TI - Caregiver burden as a predictor of depression among family and friends who provide care for persons with bipolar disorder. AB - OBJECTIVES: Over one-third of caregivers of people with bipolar disorder report clinically significant levels of depressive symptoms. This study examined the causal relationship between depression and caregiver burden in a large sample of caregivers of adult patients with bipolar disorder. METHODS: Participants were 500 primary caregivers of persons with bipolar disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).This study evaluates the strength and direction of the associations between caregiver burden and depressive symptoms at baseline and at six- and 12-month follow-up using cross-lagged panel analyses, controlling for the clinical status of patients and sociodemographic variables. RESULTS: Higher levels of overall caregiver burden at baseline were associated with increased levels of depressive symptoms among caregivers at follow-up (F = 8.70, df = 1,290, p < 0.001), after controlling for baseline caregiver depression, gender, race, age, social support, and patients' clinical status. By contrast, caregiver depression at baseline was not significantly associated with caregiver burden at follow-up (F = 1.65, p = 0.20). CONCLUSIONS: Caregiver burden is a stronger predictor of caregiver depressive symptoms over time than the reverse. Interventions that help alleviate caregiver burden may decrease depressive symptoms. PMID- 27004623 TI - Emergent Catalytic Behavior of Self-Assembled Low Molecular Weight Peptide-Based Aggregates and Hydrogels. AB - We report a series of short peptides possessing the sequence (FE)n or (EF)n and bearing l-proline at their N-terminus that self-assemble into high aspect ratio aggregates and hydrogels. We show that these aggregates are able to catalyze the aldol reaction, whereas non-aggregated analogues are catalytically inactive. We have undertaken an analysis of the results, considering the accessibility of catalytic sites, pKa value shifts, and the presence of hydrophobic pockets. We conclude that the presence of hydrophobic regions is indeed relevant for substrate solubilization, but that the active site accessibility is the key factor for the observed differences in reaction rates. The results presented here provide an example of the emergence of a new chemical property caused by self assembly, and support the relevant role played by self-assembled peptides in prebiotic scenarios. In this sense, the reported systems can be seen as primitive aldolase I mimics, and have been successfully tested for the synthesis of simple carbohydrate precursors. PMID- 27004624 TI - The use of force-plate posturography in the assessment of postural instability. AB - Force-plate posturography is a simple method that is commonly used in the contemporary laboratory and clinic to assess postural control. Despite the obvious advantages and popularity of the method, universal standards for posturographic tests have not been developed thus far: most postural assessments are based on the standard spatiotemporal metrics of the center-of-foot pressure (COP) recorded during quiet stance. Unfortunately, the standard COP characteristics are strongly dependent on individual experimental design and are susceptible to distortions such as the noise of signal digitalization, which often makes the results from different laboratories incomparable and unreliable. The COP trajectories were recorded in subjects standing still, with eyes open (EO) and then, with eyes closed (EC). The 168 subjects were divided into 3 experimental groups: young adults, older adults, and patients with Parkinson's disease. Three novel output measures: the sway directional index (DI), the sway ratio (SR), and the sway vector (SV) were applied to assess the postural stability in the experimental groups. The controlled variables: age, pathology, and visual conditions, uniquely affected the output measures. The basic attributes of the SV: its reference position, magnitude, and azimuth, provided a unique set of descriptors for postural control that allowed me unambiguously to differentiate the decline in postural stability caused by natural ageing and Parkinson's disease. As shown in previous investigations, the SV attributes, when optimally filtered with a low-pass filter, were highly independent of the trial length and the sampling frequency, and were unaffected by the sampling noise. In conclusion, the SV may be recommended as the useful standard in static posturography. PMID- 27004626 TI - Instrumented shoes for activity classification in the elderly. AB - Quantifying daily physical activity in older adults can provide relevant monitoring and diagnostic information about risk of fall and frailty. In this study, we introduce instrumented shoes capable of recording movement and foot loading data unobtrusively throughout the day. Recorded data were used to devise an activity classification algorithm. Ten elderly persons wore the instrumented shoe system consisting of insoles inside the shoes and inertial measurement units on the shoes, and performed a series of activities of daily life as part of a semi-structured protocol. We hypothesized that foot loading, orientation, and elevation can be used to classify postural transitions, locomotion, and walking type. Additional sensors worn at the right thigh and the trunk were used as reference, along with an event marker. An activity classification algorithm was built based on a decision tree that incorporates rules inspired from movement biomechanics. The algorithm revealed excellent performance with respect to the reference system with an overall accuracy of 97% across all activities. The algorithm was also capable of recognizing all postural transitions and locomotion periods with elevation changes. Furthermore, the algorithm proved to be robust against small changes of tuning parameters. This instrumented shoe system is suitable for daily activity monitoring in elderly persons and can additionally provide gait parameters, which, combined with activity parameters, can supply useful clinical information regarding the mobility of elderly persons. PMID- 27004625 TI - Effect of three cueing devices for people with Parkinson's disease with gait initiation difficulties. AB - BACKGROUND: Freezing of gait (FOG) remains one of the most common debilitating aspects of Parkinson's disease and has been linked to injuries, falls and reduced quality of life. Although commercially available portable cueing devices exist claiming to assist with overcoming freezing; their immediate effectiveness in overcoming gait initiation failure is currently unknown. This study investigated the effects of three different types of cueing device in people with Parkinson's disease who experience freezing. METHODS: Twenty participants with idiopathic Parkinson's disease who experienced freezing during gait but who were able to walk short distances indoors independently were recruited. At least three attempts at gait initiation were recorded using a 10 camera Qualisys motion analysis system and four force platforms. Test conditions were; Laser Cane, sound metronome, vibrating metronome, walking stick and no intervention. RESULTS: During testing 12 of the 20 participants had freezing episodes, from these participants 100 freezing and 91 non-freezing trials were recorded. Clear differences in the movement patterns were seen between freezing and non-freezing episodes. The Laser Cane was most effective cueing device at improving the forwards/backwards and side to side movement and had the least number of freezing episodes. The walking stick also showed significant improvements compared to the other conditions. The vibration metronome appeared to disrupt movement compared to the sound metronome at the same beat frequency. CONCLUSION: This study identified differences in the movement patterns between freezing episodes and non freezing episodes, and identified immediate improvements during gait initiation when using the Laser Cane over the other interventions. PMID- 27004627 TI - Foot-related pain and disability and spatiotemporal parameters of gait during self-selected and fast walking speeds in people with gout: A two-arm cross sectional study. AB - OBJECTIVES: To examine gait parameters in people with gout during different walking speeds while adjusting for body mass index (BMI) and foot-pain, and to determine the relationship between gait parameters and foot-pain and disability. METHOD: Gait parameters were measured using the GAITRiteTM walkway in 20 gout participants and 20 age- and sex-matched controls during self-selected and fast walking speeds. Foot-pain and disability was measured using the Manchester Foot Pain and Disability Index (MFPDI) which contains four domains relating to function, physical appearance, pain and work/leisure. RESULTS: At the self selected speed, gout participants demonstrated increased step time (p=0.017), and stance time (p=0.012), and reduced velocity (p=0.031) and cadence (p=0.013). At the fast speed, gout participants demonstrated increased step time (p=0.007), swing time (p=0.005) and stance time (p=0.019) and reduced velocity (p=0.036) and cadence (p=0.009). For participants with gout, step length was correlated with total MFPDI (r=-0.62, p=0.008), function (r=-0.65, p=0.005) and physical appearance (r=-0.50, p=0.041); stride length was correlated with total MFPDI (r= 0.62, p=0.008), function (r=-0.65, p=0.005) and physical appearance (r=-0.50, p=0.041); and velocity was correlated with total MFPDI (r=-0.60, p=0.011), function (r=-0.63, p=0.007) and work/leisure (r=-0.53, p=0.030). CONCLUSION: Gait patterns exhibited by people with gout are different from controls during both self-selected and fast walking speeds, even after adjusting for BMI and foot pain. Additionally, gait parameters were strongly correlated with patient reported functional limitation, physical appearance and work/leisure difficulties, while pain did not significantly influence gait in people with gout. PMID- 27004628 TI - Comparison of physical activity assessed using hip- and wrist-worn accelerometers. AB - OBJECTIVES: It is unclear how physical activity estimates differ when assessed using hip- vs wrist-worn accelerometers. The objective of this study was to compare physical activity assessed by hip- and wrist-worn accelerometers in free living older women. DESIGN: A cross-sectional study collecting data in free living environment. METHODS: Participants were from the Women's Health Study, in which an ancillary study is objectively measuring physical activity using accelerometers (ActiGraph GT3X+). We analyzed data from 94 women (mean (SD) age=71.9 (6.0) years) who wore a hip-worn and wrist-worn accelerometers simultaneously for 7 days. RESULTS: Using triaxial data (vector magnitude, VM), total activity volume (counts per day) between the two locations was moderately correlated (Spearman's r=0.73). Hip and wrist monitors wear locations identically classified 71% individuals who were at the highest 40% or lowest 40% of their respective distributions. Similar patterns and slightly stronger agreements were observed when examining steps instead of VM counts. CONCLUSIONS: Accelerometer assessed physical activity using hip- vs wrist-worn devices was moderately correlated in older, free-living women. However, further research needs to be conducted to examine comparisons of specific activities or physical activity intensity levels. PMID- 27004629 TI - Effects of an auditory biofeedback device on plantar pressure in patients with chronic ankle instability. AB - Chronic ankle instability (CAI) patients have been shown to have increased lateral column plantar pressure throughout the stance phase of gait. To date, traditional CAI rehabilitation programs have been unable to alter gait. We developed an auditory biofeedback device that can be worn in shoes that elicits an audible cue when an excessive amount of pressure is applied to a sensor. This study determined whether using this device can decrease lateral plantar pressure in participants with CAI and alter surface electromyography (sEMG) amplitudes (anterior tibialis, peroneus longus, medial gastrocnemius, and gluteus medius). Ten CAI patients completed baseline treadmill walking while in-shoe plantar pressures and sEMG were measured (baseline condition). Next, the device was placed into the shoe and set to a threshold that would elicit an audible cue during each step of the participant's normal gait. Then, participants were instructed to walk in a manner that would not trigger the audible cue, while plantar pressure and sEMG measures were recorded (auditory feedback (AUD FB) condition). Compared to baseline, there was a statistically significant reduction in peak pressure in the lateral midfoot-forefoot and central forefoot during the AUD FB condition. In addition, there were increases in peroneus longus and medial gastrocnemius sEMG amplitudes 200 ms post-initial contact during the AUD FB condition. The use of this auditory biofeedback device resulted in decreased plantar pressure in the lateral column of the foot during treadmill walking in CAI patients and may have been caused by the increase in sEMG activation of the peroneus longus. PMID- 27004630 TI - Reliability and minimal detectable change of gait kinematics in people who are hypermobile. AB - OBJECTIVE: To evaluate intra- and inter-session reliability of gait data in hypermobile and normal adults, and from this, determine the minimum detectable change (MDC) through 3D gait analysis (GA) measurement. METHODS: Thirteen people with normal flexibility (Beighton score 0.82 +/- 1.2) and 14 hypermobile people (Beighton score 5.6 +/- 1.6) completed three separate GA sessions. Lower limb joint kinematics were recorded in three planes of motion. Intra- and inter session variability was calculated and compared using single factor ANOVA. MDC at 95% confidence level was calculated for the hypermobile cohort. RESULTS: There was no significant difference between hypermobile and normal flexibility adults in intra- or inter-session variability for any parameters measured. For both groups, mean intra-session variability was under 2.0 degrees for all joints in all three planes. Inter-session variability was greater; sagittal plane joint angles were most reliable, showing less than 3.0 degrees variability for all joints. Frontal plane variability was below 3.5 degrees . Highest variability was seen in internal/external rotation angles, with hip, knee and ankle showing 4.6 degrees , 5.1 degrees and 3.2 degrees variability respectively. These reliability values are reflected in MDC results, with pelvis and sagittal plane joint angles showing the lowest MDCs. CONCLUSIONS: In hypermobile people, 3DGA kinematic parameters are repeatable. Hypermobile people's joint laxity does not affect variability of their kinematic gait analysis measures. The results will help guide future clinical trial design; future work should ensure that differences expected to be observed are measurable, and exceed the MDC for a given parameter. PMID- 27004631 TI - Effect of footwear on minimum foot clearance, heel slippage and spatiotemporal measures of gait in older women. AB - Footwear has been implicated as a factor in falls, which is a major issue affecting the health of older adults. This study investigated the effect of footwear with dorsal fixation, slippers and bare feet on minimum foot clearance, heel slippage and spatiotemporal variables of gait in community dwelling older women. Thirty women participated (mean age (SD) 69.1 (5.1) years) in a gait assessment using the GaitRITE and Vicon 612 motion analysis system. Conditions included footwear with dorsal fixation, slippers or bare feet. Footwear with dorsal fixation resulted in improved minimum foot clearance compared to the slippers and bare feet conditions and less heel slippage than slippers and an increase in double support. These features lend weight to the argument that older women should be supported to make footwear choices with optimal fitting features including dorsal fixation. Recommendations of particular styles and features of footwear may assist during falls prevention education to reduce the incidence of foot trips and falls. PMID- 27004632 TI - Regression models to predict hip joint centers in pathological hip population. AB - The purpose was to investigate the validity of Harrington's and Davis's hip joint center (HJC) regression equations on a population affected by a hip deformity, (i.e., femoroacetabular impingement). Sixty-seven participants (21 healthy controls, 46 with a cam-type deformity) underwent pelvic CT imaging. Relevant bony landmarks and geometric HJCs were digitized from the images, and skin thickness was measured for the anterior and posterior superior iliac spines. Non parametric statistical and Bland-Altman tests analyzed differences between the predicted HJC (from regression equations) and the actual HJC (from CT images). The error from Davis's model (25.0 +/- 6.7 mm) was larger than Harrington's (12.3 +/- 5.9 mm, p<0.001). There were no differences between groups, thus, studies on femoroacetabular impingement can implement conventional regression models. Measured skin thickness was 9.7 +/- 7.0mm and 19.6 +/- 10.9 mm for the anterior and posterior bony landmarks, respectively, and correlated with body mass index. Skin thickness estimates can be considered to reduce the systematic error introduced by surface markers. New adult-specific regression equations were developed from the CT dataset, with the hypothesis that they could provide better estimates when tuned to a larger adult-specific dataset. The linear models were validated on external datasets and using leave-one-out cross-validation techniques; Prediction errors were comparable to those of Harrington's model, despite the adult-specific population and the larger sample size, thus, prediction accuracy obtained from these parameters could not be improved. PMID- 27004633 TI - How does the extent of central visual field loss affect adaptive gait? AB - Visual impairment is one of the most important clinical risk factors associated with falls. Currently it remains unclear whether adaptive gait is progressively affected as the extent of central visual field loss (CFL) increases, or when CFL exceeds a certain size. 10 participants (aged 22 +/- 3 years) negotiated a floor based obstacle in full vision (no occlusion) and wearing custom made contact lenses which simulated 10 degrees CFL and 20 degrees CFL. Movement kinematics assessed the period immediately prior to and during obstacle crossing. In the 20 degrees CFL condition, participants exhibited adaptations in gait which were consistent with being more cautious and more variable during the approach to and crossing of the obstacle, when compared to both 10 degrees CFL and full vision conditions. Specifically, in the 20 degrees CFL condition participants placed their lead foot further from the obstacle, lifted both their lead and trail feet higher and slower over the obstacle, and took longer to negotiate the obstacle when compared to the 10 degrees CFL and full vision conditions. Data highlights differences in adaptive gait as a function of the extent of CFL when compared to full vision. More importantly, these adaptations were only associated with loss of the central 20 degrees of the visual field, suggesting that gait is compromised only after central visual field loss exceeds a certain level. PMID- 27004634 TI - The role of altered proximal femoral geometry in impaired pelvis stability and hip control during CP gait: A simulation study. AB - Children with cerebral palsy (CP) often present aberrant hip geometry, more specifically increased femoral anteversion and neck-shaft angle. Furthermore, altered gait patterns are present within this population. This study analyzed the effect of aberrant femoral geometry, as present in subjects with CP, on the ability of muscles to control hip and knee joint kinematics. Given the specific gait deficits observed during crouch gait, increased ability to abduct, externally rotate the hip and extend the knee and hip were denoted as beneficial effects. We ran dynamic simulations of CP and normal gait using two musculoskeletal models, one reflecting normal femoral geometry and one reflecting proximal femoral deformities. The results show that the combination of aberrant bone geometry and CP-specific gait characteristics beneficially increased the ability of gluteus medius and maximus to extend the hip and knee. In contrast, the potentials of the hamstrings to extend the hip decreased whereas the potentials to flex the knee increased. These changes closely followed the observed changes in the muscle moment arm lengths. In conclusion, this study emphasizes the concomitant effect of the presence of proximal femoral deformity and CP gait characteristics on the muscle control of hip and knee joint kinematics during single stance. Not accounting for subject-specific geometry will affect the calculated muscles' potential during gait. Therefore, the use of generic models to assess muscle function in the presence of femoral deformity and CP gait should be treated with caution. PMID- 27004635 TI - Comprehensive non-dimensional normalization of gait data. AB - Normalizing clinical gait analysis data is required to remove variability due to physical characteristics such as leg length and weight. This is particularly important for children where both are associated with age. In most clinical centres conventional normalization (by mass only) is used whereas there is a stronger biomechanical argument for non-dimensional normalization. This study used data from 82 typically developing children to compare how the two schemes performed over a wide range of temporal-spatial and kinetic parameters by calculating the coefficients of determination with leg length, weight and height. 81% of the conventionally normalized parameters had a coefficient of determination above the threshold for a statistical association (p<0.05) compared to 23% of those normalized non-dimensionally. All the conventionally normalized parameters exceeding this threshold showed a reduced association with non dimensional normalization. In conclusion, non-dimensional normalization is more effective that conventional normalization in reducing the effects of height, weight and age in a comprehensive range of temporal-spatial and kinetic parameters. PMID- 27004636 TI - Does surgical approach or prosthesis type affect hip joint loading one year after surgery? AB - Several approaches may be used for hip replacement surgery either in combination with conventional total hip arthroplasty (THA) or resurfacing hip arthroplasty (RHA). This study investigates the differences in hip loading during gait one year or more after surgery in three cohorts presenting different surgical procedures, more specific RHA placed using the direct lateral (RHA-DLA, n=8) and posterolateral (RHA-PLA, n=14) approach as well as THA placed using the direct anterior (THA-DAA, n=12) approach. For the DAA and control subjects, hip loading was also evaluated during stair ascent and descent to evaluate whether these motions can better discriminate between patients and controls compared to gait. Musculoskeletal modelling in OpenSim was used to calculate in vivo joint loading. Results showed that for all operated patients, regardless the surgical procedure, hip loading was decreased compared to control subjects, while no differences were found between patient groups. This indicates that THA via DAA results in similar hip loading as a RHA via DLA or PLA. Stair climbing did not result in more distinct differences in hip contact force magnitude between patients and controls, although differences in orientation were more distinct. However, patients after hip surgery did adjust their motion pattern to decrease the magnitude of loading on the hip joint compared to control subjects. PMID- 27004637 TI - Motion analysis of axial rotation and gait stability during turning in people with Parkinson's disease. AB - BACKGROUND: Axial rigidity and postural instability in people with Parkinson's disease (PD) may contribute to turning difficulty. This study examined the rotation of axial segments and gait instability during turning in people with PD. METHODS: Thirteen PD and twelve age-matched healthy adults were recruited. Participants performed the timed Up-and-Go test and were recorded by a 3D motion capture system. Axial rotation was evaluated by the rotation onset of the head, thorax and pelvis. Gait stability was evaluated by the center of mass and center of pressure inclination angle. Turning performance was evaluated by turning time and turning steps. RESULTS: During turning, PD adults rotated the head, thorax and pelvis simultaneously, whereas healthy adults rotated in a cranial to caudal sequence. Further, PD adults had a smaller sagittal inclination angle (p<0.001) but larger frontal inclination angle (p=0.006) than healthy adults. PD adults also turned slower (p=0.002) with a greater number of steps (p<0.001) than healthy adults. Last, PD adults showed a significant correlation between the sagittal inclination angle and turning steps (Spearman's rho=-0.63), while healthy adults showed a significant correlation between frontal inclination angle and turning steps (Spearman's rho=-0.67). CONCLUSION: This study demonstrated the axial rigidity in PD adults during turning may reduce forward progression and increase lateral instability. The reduced progression is associated with extra turning steps and the increased lateral instability may result in great fall risk. PMID- 27004638 TI - Association of trunk control with mobility performance and accelerometry-based gait characteristics in hemiparetic patients with subacute stroke. AB - Trunk control plays an important role in movement control and postural balance during functional activities. The purpose of this study was to investigate the association of trunk control early after stroke with mobility performance and quantitative gait characteristics derived from trunk accelerations. Fifteen patients with hemiparesis following stroke (median age, 61 years [range, 56-78 years]; median time since stroke, 9 days [range, 7-15 days]) participated in this cross-sectional observational study. Subjects were evaluated using the Trunk Impairment Scale (TIS), the short-form of the Berg Balance Scale (SF-BBS), an isometric knee extension strength test, the Timed Up and Go test (TUG), and a timed walking test. The linear acceleration of the lower trunk was recorded along the 3 axes during walking and quantified using the autocorrelation coefficient and harmonic ratio to assess the variability and smoothness of upper-body movement. The TIS total score had a significant correlation with TUG time. The coordination subscale score of the TIS was significantly correlated with TUG time, walking speed, and accelerometry variables in univariate analysis. The TIS coordination subscale score was significantly related to accelerometry variables in the partial correlation analysis adjusted for SF-BBS score and knee extension strength on the paretic and nonparetic side. These results indicate that trunk motor impairment after stroke is closely associated with poor mobility performance and trunk instability in gait. These findings support intensive rehabilitation treatment targeting trunk control to regain better mobility and stable gait in patients early after stroke. PMID- 27004639 TI - The test-retest reliability and minimal detectable change of spatial and temporal gait variability during usual over-ground walking for younger and older adults. AB - Gait variability is a marker of gait performance and future mobility status in older adults. Reliability of gait variability has been examined mainly in community dwelling older adults who are likely to fluctuate over time. The purpose of this study was to compare test-retest reliability and determine minimal detectable change (MDC) of spatial and temporal gait variability in younger and older adults. Forty younger (mean age=26.6 +/- 6.0 years) and 46 older adults (mean age=78.1 +/- 6.2 years) were included in the study. Gait characteristics were measured twice, approximately 1 week apart, using a computerized walkway (GaitMat II). Participants completed 4 passes on the GaitMat II at their self-selected walking speed. Test-retest reliability was calculated using Intra-class correlation coefficients (ICCs(2,1)), 95% limits of agreement (95% LoA) in conjunction with Bland-Altman plots, relative limits of agreement (LoA%) and standard error of measurement (SEM). The MDC at 90% and 95% level were also calculated. ICCs of gait variability ranged 0.26-0.65 in younger and 0.28 0.74 in older adults. The LoA% and SEM were consistently higher (i.e. less reliable) for all gait variables in older compared to younger adults except SEM for step width. The MDC was consistently larger for all gait variables in older compared to younger adults except step width. ICCs were of limited utility due to restricted ranges in younger adults. Based on absolute reliability measures and MDC, younger had greater test-retest reliability and smaller MDC of spatial and temporal gait variability compared to older adults. PMID- 27004640 TI - Gait dynamics when wearing a treadmill safety harness. AB - Nonlinear dynamics quantifies gait variability patterns, which can be useful in evaluating functional ability. A commonly used nonlinear technique is detrended fluctuation analysis (DFA). Safety support structures have previously been shown to alter DFA during gait. However, the effect of a nonweight-supporting treadmill harness on DFA during gait has yet to be determined. The purpose of this study was to determine whether a nonweight-supporting harness influenced the DFA alpha metric (DFA alpha) of variables typically used to examine gait function. Twenty participants (10 young adults and 10 older adults) were recruited for this study. Each participant completed one testing session on a treadmill consisting of three conditions: (1) no harness, (2) harnessed, but not attached to the support frame, and (3) harnessed and attached to the support frame. Participants walked for 15 min at the same self-selected speed for each condition. The gait variables of stride time, stride length, and step width for each condition were analyzed using DFA alpha to examine gait function. There were no significant interactions between age group and condition for DFA alpha of each variable. Additionally, there were no main effects for DFA alpha for age group or condition. These data indicate that a nonweight-supporting harness can be used for safety without impeding the emergence of natural gait dynamics when stride time, stride length, and step width are the primary variables of interest. PMID- 27004641 TI - Between-day reliability of triceps surae responses to standing perturbations in people post-stroke and healthy controls: A high-density surface EMG investigation. AB - The reliability of triceps surae electromyographic responses to standing perturbations in people after stroke and healthy controls is unknown. High Density surface Electromyography (HDsEMG) is a technique that records electromyographic signals from different locations over a muscle, overcoming limitations of traditional surface EMG such as between-day differences in electrode placement. In this study, HDsEMG was used to measure responses from soleus (SOL, 18 channels) and medial and lateral gastrocnemius (MG and LG, 16 channels each) in 10 people after stroke and 10 controls. Timing and amplitude of the response were estimated for each channel of the grids. Intraclass Correlation Coefficient (ICC) and normalized Standard Error of Measurement (SEM%) were calculated for each channel individually (single-channel configuration) and on the median of each grid (all-channels configuration). Both timing (single channel: ICC=0.75-0.96, SEM%=5.0-9.1; all-channels: ICC=0.85-0.97; SEM%=3.5-6.2%) and amplitude (single-channel: ICC=0.60-0.91, SEM%=25.1-46.6; ICC=0.73-0.95, SEM%=19.3-42.1) showed good-to-excellent reliability. HDsEMG provides reliable estimates of EMG responses to perturbations both in individuals after stroke and in healthy controls; reliability was marginally better for the all-channels compared to the single-channel configuration. PMID- 27004642 TI - Rehabilitation of gait in patients after total hip arthroplasty: Comparison of the minimal invasive Yale 2-incision technique and the conventional lateral approach. AB - The minimal invasive anterolateral Yale 2-incision approach for total hip arthroplasty aims minimizing damage to the muscles for faster recovery of function. Therefore the hypothesis was investigated, that during the rehabilitation process the Yale approach shows a faster return to natural gait than a conventional lateral approach. Nineteen patients had the Yale, 16 the conventional Bauer approach. Instrumented gait analysis was performed 3 days, 3 and 12 month post operatively. Velocity, cadence, step length, weight bearing, thorax lean, Trendelenburg limp, hip abduction moments, and hip muscle activation times were evaluated. Three days post-surgery a significantly greater loading of the treated limb and increased hip abduction moment were observed in the Yale group. In addition, the Yale group showed its greatest improvement in walking speed and step length between at 3 days and 3 months, whereas the conventional group showed an additional significant gain between 3 and 12 month to reach a similar walking speed as the Yale group. For all hip muscles investigated, only muscle tensor fasciae latae in the conventional group showed a significant increase in activation time between 3 days and 3 months. This study showed significantly faster return to natural gait in the Yale compared to the conventional approach, which could be biomechanically related to less impairment of abductor muscles in the Yale approach. PMID- 27004643 TI - Age-related changes in postural sway in preschoolers. AB - OBJECTIVES: The present study aimed to investigate age-related differences of postural sway in 3- to 6-year-old typically developing children in different sensory conditions and subsequently to provide reference values for global descriptive sway parameters in preschoolers. METHODS: Ninety-six typically developing children, between 3 and 5 years of age, participated in this cross sectional study. Postural sway was measured for 40s in four conditions (eyes open/eyes closed on stable ground/foam) by using a force plate. Global descriptive sway parameters were calculated and analysed using a 2 * 2 * 3 (surface * vision * age group) MANOVA (p<0.05) in the children that were able to complete the task (40s). RESULTS: When sensory information was altered, a significantly smaller number of 3- and 4-year-olds was able to complete the task. Significant main effects of vision (p<0.05), surface (p<0.001) and an interaction effect between vision and surface (p<0.05) on all postural sway parameters were found. A significant main effect of age was found for antero-posterior amplitude (p=0.047), medio-lateral root mean square (p=0.012) and area (p=0.009) between 3- and 5-year-olds and 4- and 5-year-olds. No interaction effects (surface * vision * age group) were found. CONCLUSIONS: During natural stance, the amount of postural sway distinguishes 5-year-olds from 3- and 4-year-olds, highlighting the need for age-specific reference values for specific balance-related sway parameters (e.g. RMS_ml). Regarding test conditions with altered sensory input, a larger number of 5-year-old children are able to perform more difficult tasks. Nevertheless, if 3- or 4-year-olds are able to perform the more difficult tasks, their performance can be compared to the older children. PMID- 27004644 TI - Balance recovery reactions in individuals with recurrent nonspecific low back pain: Effect of attention. AB - People who suffer from Low Back Pain (LBP) demonstrate impaired postural control. Deficits in sensory-motor systems have been proposed to be related to these changes. Considering higher cognitive process contribution to postural control, the aim of this study was to investigate the effects of cognitive load on balance control of patients with LBP. Twenty subjects with recurrent non-specific LBP and 20 healthy controls participated. They stood on a moveable platform with each foot placed on a separate force plate. They were asked to maintain their balance (a) while expecting translations of the support surface at two sizes of perturbation (b) with and without performing a cognitive (auditory Stroop) task. The outcomes included reaction time (RT), latency, initial velocity and amplitude of center of pressure response for balance, and RT for cognitive performance. Compared to the healthy group, LBP group demonstrated delayed RT and latency, and reduced initial velocity (P<0.05). Moreover, they had slower Stroop RT (F=70.88, P<0.001). Concurrent performance of tasks resulted in increased Stroop RT (F=3.42, P=0.03) and adaptation in initial velocity (F=6.70, P=0.01). At the smaller size of perturbation, cognitive load increased velocity in LBP group but decreased this variable in the healthy group. When the cognitive load was added at the larger size of perturbation, velocity of response decreased in LBP group (P<0.05). These findings imply altered cognitive regulation of dynamic balance in patients with LBP and suggest that the adopted strategy might alter depending upon the characteristics of the postural challenge. PMID- 27004645 TI - Reflex ankle stiffness is inversely correlated with natural body sway. AB - We aimed to determine whether effective ankle stiffness (EAS), measured during slow unperceived perturbations of stance, is related to natural anterior posterior body sway. Because the perturbations are not perceived, any neural component of the response to perturbation is assumed to be "reflex", in the broad sense of an involuntary response to a stimulus. Subjects stood on a force platform for three 10-min trials. EAS was obtained from the average slope (Deltatau/Deltaalpha) of the relation between ankle torque (tau) and ankle angle (alpha), recorded during repeated perturbations delivered at the waist by a weak spring. EAS was normalised using the subject's "load stiffness" (LS), calculated from mass (m) and height (h) above the ankle joint (m.g.h). Sway was obtained from fluctuations in ankle angle prior to perturbation. Variation in EAS and sway between subjects provided spread of data for correlation. There were no significant changes in EAS or sway across trials. All subjects had higher EAS than LS and mean EAS (1124 N m/rad) was significantly greater (p<0.01) than mean LS (531 N m/rad). There was a strong significant inverse correlation between mean sway and mean normalised EAS (r=-0.68, p=0.03). We conclude that the body, in response to slow unperceived perturbations, simulates an inverted pendulum with a stiffness of about twice LS and that EAS is largely generated by neural modulation of postural muscles. The inverse correlation between EAS and body sway suggests that the reflex mechanisms responding to perturbation also influence the extent of natural sway. PMID- 27004646 TI - Ambulation speed and corresponding mechanics are associated with changes in serum cartilage oligomeric matrix protein. AB - Because serum cartilage oligomeric matrix protein (COMP) has been used to reflect articular cartilage condition, we aimed to identify walking and running mechanics that are associated with changes in serum COMP. Eighteen subjects (9 male, 9 female; age=23 +/- 2 yrs.; mass=68.3 +/- 9.6 kg; height=1.70 +/- 0.08 m) completed 4000 steps on an instrumented treadmill on three separate days. Each day corresponded to a different ambulation speed: slow (preferred walking speed), medium (+50% of slow), and fast (+100% of slow). Synchronized ground reaction force and video data were collected to evaluate walking mechanics. Blood samples were collected pre-, post-, 30-minute post-, and 60-minute post-ambulation to determine serum COMP concentration at these times. Serum COMP increased 29%, 18%, and 5% immediately post ambulation for the fast, medium, and slow sessions (p<0.01). When the speeds were pooled, peak ankle inversion, knee extension, knee abduction, hip flexion, hip extension, and hip abduction moment, and knee flexion angle at impact explained 61.4% of total variance in COMP concentration change (p<0.001). These results indicate that (1) certain joint mechanics are associated with acute change in serum COMP due to ambulation, and (2) increased ambulation speed increases serum COMP concentration. PMID- 27004647 TI - The effect of footwear and footfall pattern on running stride interval long-range correlations and distributional variability. AB - The presence of long-range correlations (self-similarity) in the stride-to-stride fluctuations in running stride interval has been used as an indicator of a healthy adaptable system. Changes to footfall patterns when running with minimalist shoes could cause a less adaptable running gait. The purpose of this study was to investigate stride interval variability and the degree of self similarity of stride interval in runners wearing minimalist and conventional footwear. Twenty-six trained habitual rearfoot footfall runners, unaccustomed to running in minimalist footwear, performed 6-min sub-maximal treadmill running bouts at 11, 13 and 15 km.h(-1) in minimalist and conventional shoes. Force sensitive resistors were placed in the shoes to quantify stride interval (time between successive foot contacts). Footfall position, stride interval mean and coefficient of variation (CV), were used to assess performance as a function of shoe type. Long-range correlations of stride interval were assessed using detrended fluctuation analysis (alpha). Mean stride interval was 1-1.3% shorter (P=0.02) and 27% of runners adopted a midfoot footfall (MFF) in the minimalist shoe. There was a significant shoe effect on alpha and shoe*speed*footfall interaction effect on CV (P<0.05). Runners that adopted a MFF in minimalist shoes, displayed reduced long-range correlations (P<0.05) and CV (P<0.06) in their running stride interval at the 15 km.h(-1) speed. The reduced variability and self-similarity observed for runners that changed to a MFF in the minimalist shoe may be suggestive of a system that is less flexible and more prone to injury. PMID- 27004648 TI - Normal aging increases postural preparation errors: Evidence from a two-choice response task with balance constraints. AB - Correlational studies indicate an association between age-related decline in balance and cognitive control, but these functions are rarely addressed within a single task. In this study, we investigate adult age differences in a two-choice response task with balance constraints under three levels of response conflict. Sixteen healthy young (20-30 years) and 16 healthy older adult participants (59 74 years) were cued symbolically (letter L vs. R) to lift either the left or the right foot from the floor in a standing position. Response conflict was manipulated by task-irrelevant visual stimuli showing congruent, incongruent, or no foot lift movement. Preparatory weight shifts (PWS) and foot lift movements were recorded using force plates and optical motion capture. Older adults showed longer response times (foot lift) and more PWS errors than younger adults. Incongruent distractors interfered with performance (greater response time and PWS errors), but this compatibility effect did not reliably differ between age groups. Response time effects of age and compatibility were strongly reduced or absent in trials without PWS errors, and for the onset of the first (erroneous) PWS in trials with preparation error. In addition, in older adults only, compatibility effects in the foot lift task correlated significantly with compatibility effects in the Flanker task. The present results strongly suggest that adult age differences in response latencies in a task with balance constraints are related to age-associated increases in postural preparation errors rather than being an epiphenomenon of general slowing. PMID- 27004649 TI - Strategies for equilibrium maintenance during single leg standing on a wobble board. AB - The aim of this study was to identify and compare movement strategies used to maintain balance while single leg standing on either a firm surface (FS) or on a wobble board (WB). In 17 healthy men, retroreflective markers were positioned on the xiphoid process and nondominant lateral malleolus to calculate trunk and contralateral-leg excursion (EXC) and velocity (VEL), and center of pressure (CoP) EXC and VEL during FS on a force platform. From the WB test, standing time (WBTIME) was determined and the board's angular EXC and VEL were calculated from four markers on the WB as surrogate measures for CoP dynamics. Electromyographic average rectified values (ARV) from eight leg and thigh muscles of the supporting limb were calculated for both tasks. WB ARV amplitudes were normalized with respect to the value of FS ARV and presented significantly higher peroneus longus and biceps femoris activity (p<0.05). WB standing time was correlated to trunk sagittal plane velocity (r=-0.73 at p=0.016) and excursion (r=-0.67 at p=0.03). CoP and WB angular movement measures were weakly and not significantly correlated between tasks. This lack of correlation indicates that WB balance maintenance requires movement beyond the ankle strategy as described for the FS task. WB standing likely demands different biomechanical and neuromuscular control strategies, which has immediate implications for the significance of WB tests in contrast to FS balance tests. Differences in control strategies will also have implications for the understanding of mechanisms for rehabilitation training using such devices. PMID- 27004650 TI - The impact of body fat on three dimensional motion of the paediatric foot during walking. AB - Childhood obesity is commonly associated with a pes planus foot type and altered lower limb joint function during walking. However, limited information has been reported on dynamic intersegment foot motion with the level of obesity in children. The aim of this study was to explore the relationships between intersegment foot motion during gait and body fat in boys age 7-11 years. Fat mass was measured in fifty-five boys using air displacement plethysmography. Three-dimensional gait analysis was conducted on the right foot of each participant using the 3DFoot model to capture angular motion of the shank, calcaneus, midfoot and metatarsals. Two multivariate statistical techniques were employed; principle component analysis reduced the multidimensional nature of gait analysis, and multiple linear regression analysis accounted for potential confounding factors. Higher fat mass predicted greater plantarflexion of the calcaneus during the first half and end of stance phase and at the end of swing phase. Greater abduction of the calcaneus throughout stance and swing was predicted by greater fat mass. At the midfoot, higher fat mass predicted greater dorsiflexion and eversion throughout the gait cycle. The findings present novel information on the relationships between intersegment angular motion of the foot and body fat in young boys. The data indicates a more pronated foot type in boys with greater body fat. These findings have clinical implications for pes planus and a predisposition for pain and discomfort during weight bearing activities potentially reducing motivation in obese children to be physically active. PMID- 27004651 TI - Exergames for unsupervised balance training at home: A pilot study in healthy older adults. AB - Exercise videogames (exergames) are gaining popularity as tools for improving balance ability in older adults, yet few exergames are suitable for home-based use. The purpose of the current pilot study was to examine the effects of a 6 week unsupervised home-based exergaming training program on balance performance. Ten community dwelling healthy older adults (age: 75.9 +/- 7.2 years) played a newly developed ice skating exergame for six weeks at home. In the game, the speed and direction of a virtual ice skater on a frozen canal were controlled using lateral weight shifts, which were captured using Kinect. Sway characteristics during quiet standing in eyes open (EO), eyes closed (EC) and dual task (DT) conditions were assessed in time and frequency domain before, and after two, four and six weeks of training. Balance was also evaluated using the narrow ridge balance test (NRBT). Multilevel modeling was applied to examine changes in balance ability. Participants played 631 (+/- 124)min over the intervention period and no subjects dropped out. Balance in terms of sway characteristics improved on average by 17.4% (EO) and 23.3% (EC) after six weeks of training (p<0.05). Differences in rate of improvement (p<0.05) were observed between participants. No intervention effects were found for quiet standing in DT conditions and on the NRBT. In conclusion, the pilot study showed that unsupervised home-based exergaming is feasible in community dwelling older adults, but also that participants do not benefit equally from the program, thereby emphasizing the need for more personalized exergame training programs. PMID- 27004652 TI - Using a goal attainment scale in the evaluation of outcomes in patients with diplegic cerebral palsy. AB - A goal attainment scale (GAS) was used to evaluate outcomes of surgical and non surgical interventions to improve gait in 45 children with diplegic cerebral palsy. Personal goals were recorded during pre-intervention gait analysis in two groups. Twenty children underwent orthopaedic surgery (Group 1) and 25 children received a non-operative intervention (Group 2). Children and/or their carers were contacted post-intervention by telephone to complete a GAS questionnaire, rating the achievement of goals on a 5-point scale. The goals were similar in both groups. The composite GAS was transformed into a standardised measure (T score) for each patient. Both groups on average achieved their goals (mean T score for Group 2 was 56.3, versus 47.1 for Group 1). The difference between these two means was significant (p=0.010). Additionally, 16 children had undergone a follow-up gait analysis during the study period, but the relationship between their Gait Profile Score and GAS was not statistically significant. Both surgical and non-surgical interventions enabled children to achieve their goals, although Group 1 reported higher achievements. The GAS reflects patient's/parent's/carer's aspirations and may be as relevant as post intervention kinematic or kinetic outcomes. PMID- 27004654 TI - The correlation between symptomatic fatigue to definite measures of gait in people with multiple sclerosis. AB - There is a general consensus relating to the multidimensional aspects of fatigue in people with multiple sclerosis (PwMS), however, the exact impact of this symptom on gait is not fully understood. Our primary aim was to examine the relationship between definite parameters of gait with self-reported symptomatic fatigue in PwMS according to their level of neurological impairment. Spatio temporal parameters of gait were studied using an electronic walkway. The Multiple Sclerosis Walking Scale (MSWS-12) questionnaire, a patient-rated measure of walking ability was collected. The Modified Fatigue Impact Scale (MFIS) questionnaire was used to determine the level of symptomatic fatigue. One hundred and one PwMS (61 women) were included in the study analysis. Subjects were divided into mild and moderate neurological impaired groups. Fatigue was correlated with 5 (out of 14) spatiotemporal parameters. However, correlation scores were all <0.35, thus considered as weak correlations. In the mild group, the double support period was the only variable positively correlated to fatigue (Spearman's rho=0.28, P=0.05). In the moderate group, step and stride length were solely negatively correlated to fatigue (Spearman's rho=0.32, P=0.03). In contrast to the definite gait parameters, the MSWS-12 self-questionnaire was moderately positively correlated to the level of fatigue. Scores for the total, mild and moderate groups were 0.54, 0.57 and 0.51; P<0.01, respectively. The present results indicate that modifications in spatio-temporal parameters of gait are not closely related to symptomatic fatigue in PwMS. On the contrary, the self reported MSWS-12 questionnaire is predisposed to level of fatigue in PwMS. PMID- 27004653 TI - Usual walking speed and all-cause mortality risk in older people: A systematic review and meta-analysis. AB - The purpose of this study was to investigate the relationship between slow usual walking speed and all-cause mortality risk in older people by conducting a meta analysis. We searched through the Pubmed, Embase and Cochrane Library database up to March 2015. Only prospective observational studies that investigating the usual walking speed and all-cause mortality risk in older adulthood approaching age 65 years or more were included. Walking speed should be specifically assessed as a single-item tool over a short distance. Pooled adjusted risk ratio (RR) and 95% confidence interval (CI) were computed for the lowest versus the highest usual walking speed category. A total of 9 studies involving 12,901 participants were included. Meta-analysis with random effect model showed that the pooled adjusted RR of all-cause mortality was 1.89 (95% CI 1.46-2.46) comparing the lowest to the highest usual walk speed. Subgroup analyses indicated that risk of all-cause mortality for slow usual walking speed appeared to be not significant among women (RR 1.45; 95% CI 0.95-2.20). Slow usual walking speed is an independent predictor of all-cause mortality in men but not in women among older adulthood approaching age 65 years or more. PMID- 27004655 TI - Changes in proprioceptive weighting during quiet standing in women with early and established knee osteoarthritis compared to healthy controls. AB - OBJECTIVES: Knee osteoarthritis (OA) is highly prevalent in people above the age of 60, and is typically associated with pain, stiffness, muscle weakness and proprioceptive deficits. Muscle-tendon vibration has been used to assess the spatial reweighting of proprioceptive input during standing. The current study aimed to investigate whether weighting of proprioceptive input is altered in patients with early and established knee OA compared to asymptomatic controls. METHODS: The upright posture of 27 participants with early OA, 26 with established OA, and 27 asymptomatic controls was perturbed by vibrating (frequency: 70Hz and amplitude: approximately 0.5mm) ankle muscles (i.e. tibialis anterior and triceps surae) and knee muscles (vastus medialis). Center of pressure displacements of the participants were recorded using a force plate. RESULTS: Both patients with early and established OA were more sensitive to triceps surae vibration compared to their healthy peers (P<0.01 for both). No such difference was found for the vibration of tibialis anterior or vastus medialis muscles between patients with knee OA and healthy controls. CONCLUSIONS: These results suggest that the early stages of knee OA may already lead to reweighting of proprioceptive information, suggesting more reliance on ankle proprioceptive input for postural control. PMID- 27004656 TI - Comparison of lateral shuffle and side-step cutting in young recreational athletes. AB - This study compared three-dimensional (3-D) hip and knee kinematics and kinetics between lateral shuffle and side-step cutting movements to determine whether the simpler lateral shuffle movement can be used in place of cutting to assess knee injury risk. A total of 78 patients (52 female) and 34 controls (16 female) aged 8-19 years performed lateral shuffle and 45 degrees side-step cutting movements. Hip and knee kinematics and kinetics between initial contact and peak knee flexion were calculated using the Plug-in-Gait model and compared between activities using Pearson's correlation and paired t-tests. Peak knee valgus angle correlated strongly (r=0.86, p<0.0001), while minimum (r=0.25, p=0.0001) and peak hip abduction (r=0.24, p=0.0003), and peak hip internal rotation (r=0.33, p<0.0001) correlated only weakly between the two activities. Peak external knee valgus moment (r=0.32, p<0.0001) and average external knee (r=0.42, p<0.0001) and hip (r=0.37, p<0.0001) flexion moments correlated weakly to moderately between activities. Subjects were more internally rotated (3.6 degrees , p<0.0001) and less abducted (16.7 degrees and 17.3 degrees for minimum and maximum, p<0.0001) at the hip during cutting, with higher hip (0.12, p<0.0001) and lower knee ( 0.02, p=0.0001) non-dimensional flexion moments. These results suggest that the lateral shuffle movement may be useful for evaluating knee valgus, particularly during initial visual assessment. However, the lateral shuffle may not be challenging enough to reveal poor neuromuscular control over hip ab/adduction and rotation, necessitating follow-up assessment of cutting, ideally using 3-D motion analysis. PMID- 27004657 TI - Comparison of temporal and stride characteristics in myotonic dystrophies type 1 and 2 during dual-task walking. AB - OBJECTIVE: We analyzed temporal and stride characteristics in patients with myotonic dystrophy type 1 (DM1) and type 2 (DM2) while performing dual mental and motor tasks, and investigated correlations between gait parameters and cognitive impairments. METHOD: Dual-task walking was performed by 37 patients (20 DM1 and 17 DM2) and 48 healthy subjects divided into two groups, age- and gender-matched control group for DM1 (HC1) and age- and gender-matched control group for DM2 (HC2). The subjects performed a basic walking task, dual-motor task, dual-mental task, and combined motor and mental task. RESULTS: DM1 and DM2 patients differed significantly in temporal and stride characteristics compared to HC. Main differences in DM1 were slower gait and shorter stride length, while both DM1 and DM2 patients had a higher degree of variation of the swing time during dual-task gait, a parameter that reflects posture and balance. Impact of the cognitive dual task on gait pattern changes was also observed. Visuospatial ability correlated with gait changes in DM1, while executive functions had stronger influence in DM2 (p<0.01). Both patient groups had leg muscle weakness. CONCLUSION: Gait pattern was impaired in both patient groups concerning temporal and stride characteristics. Dual-task walking paradigm may discover mild initial gait changes and could provide early identification of fall risks and predict possible falls in DM patients. PMID- 27004658 TI - The reliability of local dynamic stability in walking while texting and performing an arithmetical problem. AB - In the recent years, local dynamic stability of walking was frequently used to quantify motor control. Particularly, dual-task paradigms are used to assess a shift in gait control strategy to test walking in real life situations. Texting short messages while walking is a common motor-cognitive dual task of daily living. To able to monitor possible intervention effects on motor-cognitive dual task performance, the test-retest reliability of the measure has to be evaluated. Since the reliability of the effects of cognitive tasks including texting while walking on local dynamic gait stability has not been assessed yet, this will be evaluated in the current study. Eleven young individuals were included. Gait data was registered twice (test-retest interval: seven days) using an inertial sensor fixed on the subjects' trunks in three conditions: normal walking, walking while texting a message and walking while reciting serials of 7. Short-term finite maximum Lyapunov Exponents were quantified to assess local dynamic stability. The test-retest reliability was calculated using intra-class correlation coefficients and Bland and Altman Plots (bias and limits of agreement). ICC values of the current study show that in normal walking and walking while texting, outcomes are comparable and indicate mostly good to excellent reliability. The reliability values were almost always the lowest in walking while reciting serials of 7. Local dynamic stability derived from kinematic data of walking while cell phone texting can be reliably collected and, in turn, be used as an outcome measure in clinical trials with repeated measures design. PMID- 27004659 TI - Does providing real-time augmented feedback affect the performance of repeated lower limb loading to exhaustion? AB - INTRODUCTION: This study aimed to determine whether real-time augmented feedback influenced performance of single-leg hopping to volitional exhaustion. METHODS: Twenty-seven healthy, male participants performed single-leg hopping (2.2 Hz) with (visual and tactile feedback for a target hop height) or without feedback on a force plate. Repeated measures ANOVA were used to determine differences in vertical stiffness (k), duration of flight (tf) and loading (tl) and vertical height displacement during flight (zf) and loading (zl). A Friedman 2-way ANOVA was performed to compare the percentage of trials between conditions that were maintained at 2.2 Hz +/- 5%. Correlations were performed to determine if the effects were similar when providing tactile or visual feedback synchronously with the audible cue. RESULTS: Augmented feedback resulted in maintenance of the tf, zf and zl between the start and end of the trials compared to hopping with no feedback (p<0.01). With or without feedback there was no change in tl and k from start to end. Without feedback, 21 of 27 participants maintained >70% of total hops at 2.2 +/- 5% Hz and this was significantly lower (p=0.01) with tactile (13/27) and visual (15/27) feedback. There was a strong correlation between tactile and visual feedback for duration of hopping cycle (Spearman's r=0.74, p <= 0.01). CONCLUSION: Feedback was detrimental to being able to maintain hopping cadence in some participants while other participants were able to achieve the cadence and target hop height. This indicates variability in the ability to use real-time augmented feedback effectively. PMID- 27004660 TI - Impaired synergic control of posture in Parkinson's patients without postural instability. AB - BACKGROUND: Postural instability is one of most disabling motor symptoms in Parkinson's disease. Indices of multi-muscle synergies are new measurements of movement and postural stability. OBJECTIVES: Multi-muscle synergies stabilizing vertical posture were studied in Parkinson's disease patients without clinical symptoms of postural instability (Hoehn-Yahr <= II) and age-matched controls. We tested the hypothesis that both synergy indices during quiet standing and synergy adjustments to self-triggered postural perturbations would be reduced in patients. METHODS: Eleven Parkinson's disease patients and 11 controls performed whole-body tasks while standing. Surface electromyography was used to quantify synergy indices stabilizing center of pressure shifts in the anterior-posterior direction during a load-release task. RESULTS: Parkinson's disease patients showed a significantly lower percentage of variance in the muscle activation space accounted for by the first four principal components, significantly reduced synergy indices during steady state, and significantly reduced anticipatory synergy adjustments (a drop in the synergy index prior to the self-triggered unloading). CONCLUSIONS: The study demonstrates for the first time that impaired synergic control in Parkinson's disease can be quantified in postural tasks, even in patients without clinical manifestations of postural instability. Synergy measurements may provide a biomarker sensitive for early problems with postural stability in Parkinson's disease. PMID- 27004661 TI - Long term gait outcomes of surgically treated idiopathic toe walkers. AB - Toe walking is a common gait deviation which in the absence of a known cause is termed idiopathic toe walking. Surgical treatment in the presence of a triceps surae contracture includes tendo-Achilles or gastrocnemius/soleus recession and has been shown to be effective in improving kinematic outcomes at a one year follow up. The purpose of this study was to assess longer term kinematic and kinetic outcomes of children with idiopathic toe walking treated surgically for gastrocnemius/soleus contractures. Eight subjects with a diagnosis of idiopathic toe walking who had surgical lengthening of the gastrocnemius/soleus and had previous motion analysis laboratory studies pre-operative and 1 year post operative, returned for a motion analysis laboratory study greater than 5 years since surgery. Subjects completed lower extremity physical exam and 3-D computerized kinematics and kinetics. Significant improvements for mean pelvic tilt, peak dorsiflexion in stance and swing, and overall kinematics index at 1 year post-operative were maintained at 5 years post-operative. Kinetic variables of ankle moment and power were improved at 1 year and 5 years post-operative. On physical exam, dorsiflexion with knee extended was tighter from 1 to 5 year follow-up which did not correspond to the functional changes of gait. Idiopathic toe walkers who were treated surgically for triceps surae contractures showed significant improvements in key kinematic and kinetic gait analysis variables at 1 year post-operative that were maintained at 5 years post-operative. Overall, subjects were satisfied with outcomes of the surgery, unrestricted in activities, and reported minimal pain. PMID- 27004662 TI - Manipulating walking path configuration influences gait variability and six minute walk test outcomes in older and younger adults. AB - This study determined whether manipulations to walking path configuration influenced six-minute walk test (6MWT) outcomes and assessed how gait variability changes over the duration of the 6MWT in different walking path configurations. Healthy older (ODR) and younger (YNG) (n=24) adults completed familiarisation trials and five randomly ordered experimental trials of the 6MWT with walking configurations of; 5, 10 and 15m straight lines, a 6m by 3m rectangle (RECT), and a figure of eight (FIG8). Six-minute walk distance (6MWD) and walking speed (m.s( 1)) were recorded for all trials and the stride count recorded for experimental trials. Reflective markers were attached to the sacrum and feet with kinematic data recorded at 100 Hz by a nine-camera motion capture system for 5m, 15m and FIG8 trials, in order to calculate variability in stride and step length, stride width, stride and step time and double limb support time. Walking speeds and 6MWD were greatest in the 15m and FIG8 experimental trials in both groups (p<0.01). Step length and stride width variability were consistent over the 6MWT duration but greater in the 5m trial vs. the 15m and FIG8 trials (p<0.05). Stride and step time and double limb support time variability all reduced between 10 and 30 strides (p<0.01). Stride and step time variability were greater in the 5m vs. 15m and FIG8 trials (p<0.01). Increasing uninterrupted gait and walking path length results in improved 6MWT outcomes and decreased gait variability in older and younger adults. PMID- 27004663 TI - A marker placement laser device for improving repeatability in 3D-foot motion analysis. AB - BACKGROUND: In 3D gait analysis, the repeated positioning of markers is associated with a high error rate, particularly when using a complex foot model with many markers. Therefore, a marker placement laser device was developed that ensures a reliable repositioning of markers. We report the development and reliability of this device for the foot at different tape conditions. METHODS: In 38 subjects, markers were placed at the foot according to the Heidelberg foot measurement method. Subjects were tested barefoot and barefoot with three different tape conditions. For all conditions, a static standing trial was captured. We analyzed differences in distances between markers and the intra class correlation coefficients (ICC). RESULTS: Small differences between the conditions (0.03-3.28 mm) and excellent ICCs (0.91-0.97 mm) were found for all parameters. CONCLUSION: The laser marker placement device appeared to be a reliable method to place markers on a tape at previously palpated positions and ensures an exact position. The device could find a wide application in different clinical research fields. PMID- 27004664 TI - Quantifying spinal gait kinematics using an enhanced optical motion capture approach in adolescent idiopathic scoliosis. AB - BACKGROUND AND PURPOSE: The pathogenesis of adolescent idiopathic scoliosis (AIS) remains poorly understood. Previous research has indicated possible relationships between kinematics of the spine, pelvis and lower extremities during gait and the progression of AIS, but adequate evidence on spinal kinematics is lacking. The aim of this study was to provide a detailed assessment of spinal gait kinematics in AIS patients compared to asymptomatic controls. METHODS: Fourteen AIS patients and 15 asymptomatic controls were included. Through introducing a previously validated enhanced trunk marker set, sagittal and frontal spinal curvature angles as well as general trunk kinematics were measured during gait using a 12-camera Vicon motion capture system. Group comparisons were conducted using T-tests and relationships between kinematic parameters and severity of scoliosis (Cobb angle) were investigated using regression analyses. RESULTS: The sagittal thoracic curvature angle in AIS patients showed on average 10.7 degrees (4.2 degrees , 17.3 degrees ) less kyphosis but 4.9 degrees (2.3 degrees , 7.6 degrees ) more range of motion (Cobb angle-dependent (R(2)=0.503)). In the frontal plane, thoracic and thoracolumbar/lumbar curvature angles indicated average lateral deviations in AIS patients. General trunk kinematics and spatio-temporal gait parameters, however, did not show any clinically relevant differences between the groups. CONCLUSIONS: This demonstrates that the dynamic functionality of the scoliotic spine can be assessed using advanced non-invasive optical approaches and that these should become standard in clinical gait analysis. Furthermore, curvature angle data might be used to drive sophisticated computer simulation models in order to gain an insight into the dynamic loading behavior of the scoliotic spine during gait. PMID- 27004665 TI - Relationship between maximum isometric joint moment and functional task performance in patients with brachial plexus injury: A pilot study. AB - We evaluated whether subjects with brachial plexus injury (BPI) adapted their movements to reduce the mechanical demand on their impaired upper extremity. In 6 subjects with unilateral BPI with C5 and C6 involvement, we measured bilateral maximum isometric shoulder and elbow strength, and computed joint kinematics and net muscle-generated joint moments during 7 unimanual functional tasks. Compared to the unimpaired extremity, maximum strength in shoulder abduction, extension, and external rotation was 60% (p=0.02), 49% (p=0.02), and 75% (p=0.02) lower, respectively, on the impaired side. Significant kinematic and kinetic differences were observed only when reaching to the back of the head. However, because of substantially reduced strength in their impaired upper extremities, subjects used a significantly higher percentage of their maximum strength during several tasks and along several directions of movement. The peak percentage of maximal strength subjects used across tasks was 32% (p=0.03) and 29% (p=0.03) more on their impaired side in shoulder extension and external rotation, respectively. Subjects had less reserve strength available for performing upper extremity tasks and, therefore, may be less adaptive to strength declines due to injury progression and normal aging. Quantitatively measuring maximal strength may help clinicians ensure that patients maintain sufficient upper extremity strength to preserve long-term functional ability. PMID- 27004666 TI - Age-related decline of gait variability in children with attention deficit/hyperactivity disorder: Support for the maturational delay hypothesis in gait. AB - BACKGROUND: Previous findings showed a tendency toward higher gait variability in children with attention-deficit/hyperactivity disorder (ADHD) compared to controls. This study examined whether gait variability in children with ADHD eventually approaches normality with increasing age (delay hypothesis) or whether these gait alterations represent a persistent deviation from typical development (deviation hypothesis). METHOD: This cross-sectional study compared 30 children with ADHD (25 boys; Mage=10 years 11 months, range 8-13 years; n=21 off medication, n=9 without medication) to 28 controls (25 boys; Mage=10 years 10 months, range 8-13 years). Gait parameters (i.e. velocity and variability in stride length and stride time) were assessed using an electronic walkway system (GAITRite) while children walked at their own pace. RESULTS: Children with ADHD walked with significantly higher variability in stride time compared to controls. Age was negatively associated with gait variability in children with ADHD such that children with higher age walked with lower variability, whereas in controls there was no such association. CONCLUSIONS: Children with ADHD displayed a less regular gait pattern than controls, indicated by their higher variability in stride time. The age-dependent decrease of gait variability in children with ADHD showed that gait performance became more regular with age and converged toward that of typically developing children. These results may reflect a maturational delay rather than a persistent deviation of gait regularity among children with ADHD compared to typically developing children. PMID- 27004667 TI - The effect of a dual task on gait speed in community dwelling older adults: A systematic review and meta-analysis. AB - BACKGROUND AND PURPOSE: Reduced walking speed in older adults is associated with adverse health outcomes. This review aims to examine the effect of a cognitive dual-task on the gait speed of community-dwelling older adults with no significant pathology affecting gait. DATA SOURCES AND STUDY SELECTION: Electronic database searches were performed in, Web of Science, PubMed, SCOPUS, Embase and psychINFO. Eligibility and methodological quality was assessed by two independent reviewers. The effect size on gait speed was measured as the raw mean difference (95% confidence interval) between single and dual-task performance. Pooled estimates of the overall effect were computed using a random effects method and forest plots generated. DATA EXTRACTION AND DATA SYNTHESIS: 22 studies (27 data sets) with a population of 3728 were reviewed and pooled for meta analysis. The mean walking speed of participants included in all studies was >1.0m/s and all studies reported the effect of a cognitive dual-task on gait speed. Sub-analysis examined the effect of type of cognitive task (mental tracking vs. verbal-fluency). Mean single-task gait speed was 1.21 (0.13)m/s, the addition of a dual-task reduced speed by 0.19 m/s to 1.02 (0.16)m/s (p<0.00001), both mental-tracking and verbal-fluency tasks resulted in significant reduction in gait speed. LIMITATIONS AND CONCLUSION: The cross-sectional design of the studies made quality assessment difficult. Despite efforts, high heterogeneity remained, possibly due to participant characteristics and testing protocols. This meta-analysis shows that in community-dwelling older adults, the addition of a dual-task significantly reduces gait speed and may indicate the value of including dual-task walking as part of the standard clinical assessment of older people. PMID- 27004668 TI - Reproducibility of gait parameters at different surface inclinations and speeds using an instrumented treadmill system. AB - Instrumented treadmill systems allow the practical assessment of gait parameters under several walking conditions. Aim of this study was to evaluate the reproducibility of gait parameters at different surface inclinations and walking speeds using an instrumented treadmill system in healthy individuals. A total of 20 subjects (10 women) with a mean age of 31 years were evaluated with an instrumented treadmill system (FDM-T, Zebris Medical GmbH) during two identical test sessions. Spatial (step length, step width, foot rotation), temporal (cadence, single-limb support, step time) and ground reaction force (heel force, toe force, time to heel force, time to toe force) gait parameters were assessed at three treadmill inclinations (level, uphill, downhill) and five speeds (2, 3, 4, 5, 6 km/h). Between-day reproducibility was evaluated with smallest detectable changes for agreement and intraclass correlation coefficients for reliability. Low agreement and reliability were observed for (i) step length, cadence and step time during slow (2 and 3 km/h) and uphill walking and (ii) time to heel force and time to toe force under the majority of walking conditions. The instrumented treadmill system used in this study provided reproducible measurements for the majority of the evaluated spatial, temporal and ground reaction force gait parameters in healthy individuals. The assessment of time to heel/toe force should be however avoided, and particular care should be taken for some spatial (step length) and temporal (cadence and step time) parameters while walking uphill and/or at slow speeds. PMID- 27004669 TI - Ischaemic stroke secondary to aortic dissection: A diagnostic challenge. PMID- 27004670 TI - Antidepressants in Parkinson's disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid. AB - INTRODUCTION: Although antidepressants are widely used in Parkinson's disease (PD), few well-designed studies to support their efficacy have been conducted. DEVELOPMENT: These clinical guidelines are based on a review of the literature and the results of an AMN movement disorder study group survey. CONCLUSIONS: Evidence suggests that nortriptyline, venlafaxine, paroxetine, and citalopram may be useful in treating depression in PD, although studies on paroxetine and citalopram yield conflicting results. In clinical practice, however, selective serotonin reuptake inhibitors are usually considered the treatment of choice. Duloxetine may be an alternative to venlafaxine, although the evidence for this is less, and venlafaxine plus mirtazapine may be useful in drug-resistant cases. Furthermore, citalopram may be indicated for the treatment of anxiety, atomoxetine for hypersomnia, trazodone and mirtazapine for insomnia and psychosis, and bupropion for apathy. In general, antidepressants are well tolerated in PD. However, clinicians should consider the anticholinergic effect of tricyclic antidepressants, the impact of serotonin-norepinephrine reuptake inhibitors on blood pressure, the extrapyramidal effects of antidepressants, and any potential interactions between monoamine oxidase B inhibitors and other antidepressants. PMID- 27004671 TI - Safe thrombolysis in astrocytoma of middle cranial fossa. PMID- 27004672 TI - Stem cells therapy in cerebral palsy: A systematic review. AB - The aim of this study was to systematically present the best available stem cell therapies for children with cerebral palsy (CP). The databases Medline, PubMed, EMBASE, and the Cochrane Controlled Trials Register for RCTs were searched for studies published from 1967 to August 2015. Systematic reviews, randomised controlled trials (RCTs), controlled trials, uncontrolled trials, cohort studies, open-label studies, and a meta-analysis were analysed. Of 360 articles, seven fulfilled the inclusion criteria: one RCT and six were open-label trials. In these studies, one application of stem cells for children with CP was typical, and the total number of cells administered to patients ranged from 10(6) to 10(8)/kg. Different routes of cell delivery were used, though in most studies motor development was applied as an indicator of primary outcomes. In three articles, neuroimaging studies were also implemented to confirm the efficacy of the therapies. Observation periods varied from 3months to 5years, and patients' tolerance of the therapy was generally good. Stem cell therapy may improve some symptoms in patients with CP, though larger studies are needed to examine the impact of stem cell therapy upon CP. PMID- 27004673 TI - High Flow Nasal Cannula Use Is Associated with Increased Morbidity and Length of Hospitalization in Extremely Low Birth Weight Infants. AB - OBJECTIVE: To determine differences in the incidence of bronchopulmonary dysplasia (BPD) or death in extremely low birth weight infants managed on high flow nasal cannula (HFNC) vs continuous positive airway pressure (CPAP). STUDY DESIGN: This is a retrospective data analysis from the Alere Neonatal Database for infants born between January 2008 and July 2013, weighing <=1000 g at birth, and received HFNC or CPAP. Baseline demographics, clinical characteristics, and neonatal outcomes were compared between the infants who received CPAP and HFNC, or HFNC +/- CPAP. Multivariable regression analysis was performed to control for the variables that differ in bivariate analysis. RESULTS: A total of 2487 infants met the inclusion criteria (941 CPAP group, 333 HFNC group, and 1546 HFNC +/- CPAP group). The primary outcome of BPD or death was significantly higher in the HFNC group (56.8%) compared with the CPAP group (50.4%, P < .05). Similarly, adjusted odds of developing BPD or death was greater in the HFNC +/- CPAP group compared with the CPAP group (OR 1.085, 95% CI 1.035-1.137, P = .001). The number of ventilator days, postnatal steroid use, days to room air, days to initiate or reach full oral feeds, and length of hospitalization were significantly higher in the HFNC and HFNC +/- CPAP groups compared with the CPAP group. CONCLUSIONS: In this retrospective study, use of HFNC in extremely low birth weight infants is associated with a higher risk of death or BPD, increased respiratory morbidities, delayed oral feeding, and prolonged hospitalization. A large clinical trial is needed to evaluate long-term safety and efficacy of HFNC in preterm infants. PMID- 27004674 TI - Development and Validation of the Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support. AB - OBJECTIVE: To develop and validate the Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support, which estimates the risk of in-hospital death for neonates prior to receiving respiratory extracorporeal membrane oxygenation (ECMO) support. STUDY DESIGN: We used an international ECMO registry (2008-2013); neonates receiving ECMO for respiratory support were included. We divided the registry into a derivation sample and internal validation sample, by calendar date. We chose candidate variables a priori based on published evidence of association with mortality; variables independently associated with mortality in logistic regression were included in this parsimonious model of risk adjustment. We evaluated model discrimination with the area under the receiver operating characteristic curve (AUC), and we evaluated calibration with the Hosmer-Lemeshow goodness-of-fit test. RESULTS: During 2008-2013, 4592 neonates received ECMO respiratory support with mortality of 31%. The development dataset contained 3139 patients treated in 2008-2011. The Neo-RESCUERS measure had an AUC of 0.78 (95% CI 0.76-0.79). The validation cohort had an AUC = 0.77 (0.75-0.80). Patients in the lowest risk decile had an observed mortality of 7.0% and a predicted mortality of 4.4%, and those in the highest risk decile had an observed mortality of 65.6% and a predicted mortality of 67.5%. CONCLUSIONS: Neonatal Risk Estimate Score for Children Using Extracorporeal Respiratory Support offers severity-of-illness adjustment for neonatal patients with respiratory failure receiving ECMO. This score may be used to adjust patient survival to assess hospital-level performance in ECMO-based care. PMID- 27004677 TI - Reply. PMID- 27004676 TI - Adrenal insufficiency exists for both swallowed budesonide and fluticasone propionate in the treatment of eosinophilic esophagitis. PMID- 27004675 TI - Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years. AB - OBJECTIVES: To compare the prevalence of cognitive, neurologic, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm. STUDY DESIGN: A total of 889 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborns Study from 2002-2004 were evaluated at 10 years of age. Children underwent a neuropsychological battery and testing for autism spectrum disorder (ASD), and parents reported on their child's behavior, development, and seizures. RESULTS: Of the children, 28% of boys and 21% of girls exhibited moderate to severe impairment on summary measures of cognitive abilities. Boys had a higher prevalence of impairment than girls in nearly all measures of cognition, were more than twice as likely to have microcephaly (15% in boys, 8% in girls), and require more often assistive devices to ambulate (6% in boys, 4% in girls). In contrast, boys and girls had comparable risk for a history of seizure (identified in 10% of the cohort) or epilepsy (identified in 7% of the cohort). The boy-to girl ratio of ASD (9% in boys, 5% in girls) was lower than expected compared with the overall US autism population. CONCLUSIONS: In this contemporary cohort of children born extremely premature and evaluated at school age, boys had higher prevalence of cognitive, neurologic, and behavioral deficits than girls. The ratio of boys to girls among those with ASD deserves further study as does the perinatal environmental-genetic interactions that might contribute to male preponderance of deficits in this high-risk sample. PMID- 27004679 TI - Letter to the Editor on "Tranexamic Acid Benefits Total Joint Arthroplasty Patients Regardless of Preoperative Hemoglobin Value". PMID- 27004678 TI - Trends in Primary and Revision Hip Arthroplasty Among Orthopedic Surgeons Who Take the American Board of Orthopedics Part II Examination. AB - BACKGROUND: A certified list of all operative cases performed within a 6-month period is a required prerequisite for surgeons taking the American Board of Orthopaedic Surgery Part II oral examination. Using the American Board of Orthopaedic Surgery secure Internet database database containing these cases, this study (1) assessed changing trends for primary and revision total hip arthroplasty (THA) and (2) compared practices and early postoperative complications between 2 groups of examinees, those with and without adult reconstruction fellowship training. METHODS: Secure Internet database was searched for all 2003-2013 procedures with a Current Procedural Terminology code for THA, hip resurfacing, hemiarthroplasty, revision hip arthroplasty, conversion to THA, or removal of hip implant (Girdlestone, static, or dynamic spacer). RESULTS: Adult reconstruction fellowship-trained surgeons performed 60% of the more than 33,000 surgeries identified (average 28.1) and nonfellowship-trained surgeons performed 40% (average 5.2) (P < .001). Fellowship-trained surgeons performed significantly more revision surgeries for infection (71% vs 29%)(P < .001). High-volume surgeons had significantly fewer complications in both primary (11.1% vs 19.6%) and revision surgeries (29% vs 35.5%) (P < .001). Those who passed the Part II examination reported higher rates of complications (21.5% vs 19.9%). CONCLUSION: In early practice, primary and revision hip arthroplasties are often performed by surgeons without adult reconstruction fellowship training. Complications are less frequently reported by surgeons with larger volumes of joint replacement surgery who perform either primary or more complex cases. Primary hip arthroplasty is increasingly performed by surgeons early in practice who have completed an adult reconstructive fellowship after residency training. This trend is even more pronounced for more complex cases such as revision or management of infection. PMID- 27004680 TI - Comparative Fixation and Subsidence Profiles of Cementless Unicompartmental Knee Arthroplasty Implants. AB - BACKGROUND: Aseptic loosening is the primary cause of failure for both cemented and cementless unicondylar knee replacements (UKRs). Micromotion and subsidence of tibial baseplate are two causes of failure, due to poor fixation and misalignment, respectively. METHODS: Stair ascent activity profiles from Bergmann et al and Li et al were used. Biphasic Sawbones models were prepared according to the surgical techniques of traditional and novel cementless UKRs. Implants were tested for 10,000 cycles representing post-operative bone interdigitation period, and micromotion was observed using speckle pattern measurements, which demonstrated sufficient resolution. Additionally, the test method proposed by Liddle et al was used to measure subsidence with pressure sensors under increasingly lateralized loading. RESULTS: Mean displacement due to micromotion for mediolateral and anteroposterior plane was consistently greater for traditional cementless UKR. Mean displacement for axial micromotion was significantly higher for traditional UKR at the anterior aspect of the implant; however, values were lower for the medial periphery of the implant. Subsidence was significantly lower for the novel design with increasingly lateralized loading, and indentation was not observed on the test substrate, when compared to the traditional design. CONCLUSION: Our findings demonstrate that the novel cementless design is capable of fixation and elimination of subsidence in laboratory test settings. Both designs limit micromotion to below the established loosening micromotion value of 150 MUm. The L-shaped keel design resists both micromotion and subsidence and may prevent failure modes that can lead to aseptic loosening for UKRs. These findings are highly relevant for clinical application. PMID- 27004681 TI - Residual Symptoms and Function in Young, Active Hip Arthroplasty Patients: Comparable to Normative Controls? AB - BACKGROUND: Whether patient-reported symptoms and function after total hip and surface replacement arthroplasty in young, active patients compare favorably to those without known hip pathology has not been investigated. METHODS: A retrospective, multicenter study was designed in which 5 centers contributed patients aged <60 years with a presymptomatic University of California at Los Angeles score >=6 undergoing hip arthroplasty. Data were collected by an independent, third-party survey center that administered a questionnaire assessing patient satisfaction and function. A "control" population with no prior hip interventions or hip pathology limiting their activity, that met the age and activity criteria, was identified for comparison using multivariate regression analyses. RESULTS: Eight-hundred six hip arthroplasties (682 total hip arthroplasty, 124 surface replacement arthroplasty) and 158 controls were included. A greater percentage of hip arthroplasty patients were male and aged >50 years which was controlled during multivariate regression analyses. Control patients reported the presence of a limp (15%), stiffness (11%), and pain in the hip (8%), but to a lesser degree than hip arthroplasty patients. Control patients were less likely to report pain in the hip (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2-0.7, P = .006), stiffness in the hip (OR = 0.5, 95% CI = 0.3 0.8, P = .02), and a limp (OR = 0.5, 95% CI = 0.3-0.8, P < .001) vs patients undergoing hip arthroplasty. CONCLUSION: When interviewed by an independent third party, a substantial portion of control patients did note the presence of hip symptoms, but to a lesser degree than young, active patients undergoing hip arthroplasty. PMID- 27004682 TI - Inhibition of the Ras-ERK pathway in mitotic COS7 cells is due to the inability of EGFR/Raf to transduce EGF signaling to downstream proteins. AB - Although previous studies have shown that Ras-ERK signaling in mitosis is closed due to the inhibition of signal transduction, the events involved in the molecular mechanisms are still unclear. In the present study, we investigated the Ras-ERK signaling pathway in mitotic COS7 cells. The results demonstrated that treatment with epidermal growth factor (EGF) failed to increase the endocytosis of EGF-EGFR (EGF receptor) complexes in mitotic COS7 cells, although a large amount of endosomes were found in asynchronous COS7 cells. Clathrin expression levels in mitotic COS7 cells were inhibited whereas caveolin expression levels in mitotic COS7 cells were almost unaffected. Y1068 and Y1086 residues of EGFR in the mitotic COS7 cells were activated. However, Grb2 and Shc in the mitotic COS7 cells did not bind to activated EGFR. Ras activity was inhibited in the mitotic COS7 cells whereas its downstream protein, Raf, was obviously phosphorylated by EGF in mitosis. Treatment with phorbol 12-myristate 13-acetate (PMA) also increased the phosphorylation levels of Raf in the mitotic COS7 cells. Nevertheless, Raf phosphorylation in mitosis was significantly inhibited by AG1478. Lastly, activation of EGF-mediated MEK and ERK in the mitotic COS7 cells was obviously inhibited. In summary, our results suggest that the Ras-ERK pathway is inhibited in mitotic COS7 cells which may be the dual result of the difficulty in the transduction of EGF signaling by EGFR or Raf to downstream proteins. PMID- 27004683 TI - Genome-wide identification of the Jatropha curcas MYB family and functional analysis of the abiotic stress responsive gene JcMYB2. AB - BACKGROUND: The MYB family is one of the most abundant transcription factor families in plants. MYB proteins are involved in plant development, abiotic stress tolerance, hormone signal transduction and disease resistance. Here we perform genome-wide identification of MYB family transcription factors in an energy plant J. curcas, including determining family composition, phylogenetic evolution and functional prediction analysis. In addition, we further elucidate the function of the JcMYB2 gene. METHODS: The phylogenetic trees were constructed by using the neighbor-joining method in MEGA 5.2. The biological functions of some JcMYBs were predicted according to orthology. The full length cDNA of JcMYB2 was cloned by using the RACE method. GUS histochemical staining was used to test the activity of the JcMYB2 promoter. Expression patterns of JcMYB2 were detected by using qPCR Transcriptional activity JcMYB2 were confirmed through yeast one hybrid. Subcellular Localization of JcMYB2 Protein were demonstrated by transient expression in the tobacco leaf. The function of JcMYB2 in salt and freezing tolerance were detected in transgenic plants. RESULTS: A genome-wide analysis identified 128 MYB genes, including 123 R2R3-MYBs, 4 R1R2R3-MYBs and 1 4R-MYB. All of the R2R3-MYBs are further classified into 19 groups which indicated functional conservation among previously identified groups of R2R3-MYB proteins. Among of these newly identified MYBs, the JcMYB2 belongs to group G11 and its expression is induced obviously by cold, salt and MeJA (Methyl Jasmonate) and slightly by ABA (abscisic acid). JcMYB2 is localized to the nucleus and has transcriptional activity. JcMYB2 overexpressing plants are more tolerant to salt and cold stress than wild type plants. Tissue specific expression profiles showed that the JcMYB2 gene was expressed ubiquitously throughout the plant, with higher expression levels observed in the root. CONCLUSION: A comprehensive genome-wide analysis and phylogenetic relationship of R2R3-MYB subfamily in J. curcas present the global identification and functional prediction of JcR2R3-MYBs. Additionally, JcMYB2 regulates the stress response signaling networks by interacting with MeJA and ABA signaling pathway and functions in the root development of J. curcas. PMID- 27004685 TI - Treatment of recurrent mediastinal lymph node metastasis using CT-guided nontranspulmonary puncture interstitial implantation of (125)I seeds: Evaluation of initial effect and operative techniques. AB - PURPOSE: To evaluate the initial effects and operative techniques for treating recurrent mediastinal lymph node metastasis using CT-guided nontranspulmonary puncture interstitial implantation of (125)I seeds. METHODS AND MATERIALS: Thirteen patients (eight men and five women) with a total of 14 recurrent mediastinal lymph node metastatic lesions underwent CT-guided nontranspulmonary puncture interstitial implantation of (125)I seeds. RESULTS: We used the transpleural cavity approach for six cases (air injection of 200-600 mL), the transsternal approach for three cases, the supersternal approach for one case, and the parasternal/paraspinal approach for the remaining cases (including two cases using the salinoma window technique). All patients had good operational tolerance. Mean followup was 16.3 months, with 12 complete response lesions and 2 partial response lesions. CONCLUSIONS: Treating recurrent mediastinal lymph node metastasis using CT-guided nontranspulmonary puncture interstitial implantation of (125)I seeds is safe and effective, with minimal trauma, evident local therapeutic effects, and does not damage lung tissue. However, comprehensive application of multiple puncture assistive technologies, and skill, is required due to the important, anatomically complex structures in the mediastinum. PMID- 27004684 TI - Clinical psychomotor skills among left and right handed medical students: are the left-handed medical students left out? AB - BACKGROUND: There is a growing perception that the left handed (LH) medical students are facing difficulties while performing the clinical tasks that involve psychomotor skill, although the evidence is very limited and diverse. The present study aimed to evaluate the clinical psychomotor skills among Right-handed (RH) and left-handed (LH) medical students. METHODS: For this study, 54 (27 left handed and 27 right handed) first year medical students were selected. They were trained for different clinical psychomotor skills including suturing, laparoscopy, intravenous cannulation and urinary catheterization under the supervision of certified instructors. All students were evaluated for psychomotor skills by different instructors. The comparative performance of the students was measured by using a global rating scale, each selected criteria was allotted 5 points score with the total score of 25. RESULTS: There were no significant differences in the performance of psychomotor skills among LH and RH medical students. The global rating score obtained by medical students in suturing techniques was: LH 15.89 +/- 2.88, RH 16.15 +/- 2.75 (p = 0.737), cannulation techniques LH 20.44 +/- 2.81, RH 20.70 +/- 2.56 (p = 0.725), urinary catheterization LH 4.33 +/- 0.96 RH 4.11 +/- 1.05 (p = 0.421). For laparoscopic skills total peg transfer time was shorter among LH medical students compared to RH medical students (LH 129.85 +/- 80.87 s vs RH 135.52 +/- 104.81 s) (p = 0.825). However, both RH and LH students completed their procedure within the stipulated time. CONCLUSIONS: Among LH and RH medical students no significant difference was observed in performing the common surgical psychomotor skills. Surgical skills for LH or RH might not be a result of innate dexterity but rather the academic environment in which they are trained and assessed. Early laterality related mentoring in medical schools as well as during the clinical residency might reduce the inconveniences faced by the left-handed medical personnel. PMID- 27004686 TI - Remote location interstitial brachytherapy with patient stabilization and subsequent transport to an outpatient center for treatment is safe and effective for the treatment of gynecologic malignancies. AB - PURPOSE: Interstitial brachytherapy is an essential component of definitive treatment for locally advanced gynecological malignancies. Although many outpatient centers are capable of delivering the radiation component of brachytherapy, they are not associated with an operative center for implant placement, limiting the ability to deliver appropriate care. In this study, we report on our experience with noncolocated implant placement and radiation delivery, and the impact of patient stabilization improvements on patient safety. METHODS AND MATERIALS: Between 9/2010 and 11/2014, 25 patients with gynecologic malignancy underwent interstitial implantation and subsequent transport for high dose-rate brachytherapy treatment. From 9/2010 to 10/2012, patients were transported using a standard ambulance stretcher; from 11/2012 to 11/2014, patients were placed on a patient positioning board or a WAFFLE support. Potential transport-associated toxicity was assessed, and the association between standard and augmented transport types and toxicity was analyzed. RESULTS: A total of 234 transports were performed. Median cost of transport was $150 per transport. There were 14 (10 patients) potential transportation-associated toxicities, including two lacerations/local trauma, three infections, and nine ulcers. There were 6 Grade 3 toxicities, all in the standard group. There was no association between stretcher type and laceration or ulcers, but enhanced support was associated with fewer overall toxicities, Grade 3 toxicities, and infections. CONCLUSIONS: Noncolocated implantation and treatment is safe and facilitates optimal therapy. Toxicities potentially associated with transport are minimal and seem to be reduced by augmented stabilization. Understanding that this is a reasonable way to deliver brachytherapy may allow more stand-alone centers to deliver high-quality care for patients and improve gynecologic cancer outcomes in the United States. PMID- 27004688 TI - Social Sensitivity and Adjustment in Chinese and Canadian Children. AB - This study examined relations of social sensitivity to socioemotional and school adjustment in Chinese and Canadian children. Participants were fourth- to eighth grade students (Mage = 12 years) in China (n = 723) and Canada (n = 568). Data were obtained from multiple sources. The analyses revealed that the pattern of relations between social sensitivity and indexes of adjustment differed in the two countries. Social sensitivity was negatively associated with social and school adjustment and positively associated with psychological distress in Canadian children. However, social sensitivity was positively associated with school competence and psychological well-being in Chinese children. The results indicate that children's social sensitivity may have different functional meanings in Chinese and North American societies. PMID- 27004687 TI - Regulation of LRRK2 promoter activity and gene expression by Sp1. AB - BACKGROUND: The dopaminergic neurodegeneration in the nigrostriatal pathway is a prominent neuropathological feature of Parkinson's disease (PD). Mutations in various genes have been linked to familial PD, and leucine-rich repeat kinase 2 (LRRK2) gene is one of them. LRRK2 is a large complex protein, belonging to the ROCO family of proteins. Recent studies suggest that the level of LRRK2 protein is one of the contributing factors to PD pathogenesis. However, it remains elusive how LRRK2 is regulated at the transcriptional and translational level. RESULTS: In this study, we cloned a 1738 bp 5'-flanking region of the human LRRK2 gene. The transcriptional start site (TSS) was located to 135 bp upstream of translational start site and the fragment -118 to +133 bp had the minimum promoter activity required for transcription. There were two functional Sp1- responsive elements on the human LRRK2 gene promoter revealed by electrophoretic mobility shift assay (EMSA). Sp1 overexpression promoted LRRK2 transcription and translation in the cellular model. On the contrary, application of mithramycin A inhibited LRRK2 transcriptional and translational activities. CONCLUSION: This is the first study indicating that Sp1 signaling plays an important role in the regulation of human LRRK2 gene expression. It suggests that controlling LRRK2 level by manipulating Sp1 signaling may be beneficial to attenuate PD-related neuropathology. PMID- 27004689 TI - Actin- and clathrin-dependent mechanisms regulate interferon gamma release after stimulation of human immune cells with respiratory syncytial virus. AB - BACKGROUND: Respiratory syncytial virus (RSV) can cause recurrent and severe respiratory tract infections. Cytoskeletal proteins are often involved during viral infections, either for cell entry or the initiation of the immune response. The importance of actin and clathrin dynamics for cell entry and the initiation of the cellular immune response against RSV in human immune cells is not known yet. The aim of this study was to investigate the role of actin and clathrin on cell entry of RSV and the subsequent effect on T cell activation and interferon gamma release in human immune cells. METHODS: Peripheral blood mononuclear cells and purified monocytes were isolated from healthy adults and stimulated in vitro with RSV. Actin and clathrin dynamics were inhibited with respectively cytochalasin D and chlorpromazine. T cell receptor signaling was inhibited with cyclosporin A. Flow cytometry was used to determine the role of actin and clathrin on cell entry and T cell activation by RSV. Enzyme-linked immunosorbent assays were used to investigate the contribution of actin and clathrin on the release of interferon gamma. RESULTS: Cell entry, virus gene transcription and interferon gamma release are actin-dependent. Post-endocytic processes like the increased expression of major histocompatibility complex II on monocytes , T cell activation and the release of interferon gamma are clathrin-dependent. Finally, T cell receptor signaling affects T cell activation, whereas soluble interleukin 18 is dispensable. CONCLUSION: Analysis of cell entry and interferon gamma release after infection with RSV reveals the importance of actin- and clathrin-dependent signaling in human immune cells. Insights into the cellular biology of the human immune response against respiratory syncytial virus will provide a better understanding of disease pathogenesis and may prove useful in the development of preventive strategies. PMID- 27004690 TI - The Evolving Landscape of Primary Immunodeficiencies. PMID- 27004692 TI - Oestrogen exerts anti-inflammation via p38 MAPK/NF-kappaB cascade in adipocytes. AB - BACKGROUND: Oestrogen has anti-inflammatory property in obesity. However, the mechanism is still not defined. OBJECTIVE: To investigate the effect of oestrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1) production in adipocytes. METHODS: Lipopolysaccharides (LPS) was used to imitate inflammatory responses and monocyte chemotactic protein-1 (MCP-1) was selected as an inflammatory marker to observe. 17beta-Estradiol (E2), SB203580 (SB), pyrrolidine dithiocarbamate (PDTC), pertussis toxin (PTX), wortmannin (WM), p65 siRNA and p38 MAPK siRNA were pre-treated respectively or together in LPS-induced MCP-1. Then p38 MAPK and NF-kappaB cascade were silenced successively to observe the change of each other. Lastly, oestrogen receptor (ER) alpha agonist, ERbeta agonist and ER antagonist were utilised. RESULTS: LPS-induced MCP-1 largely impaired by pre treatment with E2, SB, PDTC or silencing NF-kappaB subunit. E2 inhibited LPS induced MCP-1 in a time- and dose-dependent manner, which was related to the suppression of p65 translocation to nucleus. Furthermore, LPS rapidly activated p38 MAPK, while E2 markedly inhibited this activation. It markedly attenuated LPS stimulated p65 translocation to nucleus and MCP-1 production by transfecting with p38 MAPK siRNA or using p38 MAPK inhibitor. The oestrogen's inhibitory effect was mimicked by the ERalpha agonist, but not by the ERbeta agonist. The inhibition of E2 on p38 MAPK phosphorylation was prevented by ER antagonist. CONCLUSIONS: E2 inhibits LPS-stimulated MCP-1 in adipocytes. This effect is related to the inhibition of p38 MAPK/NF-kappaB cascade, and ERalpha appears to be the dominant ER subtype in these events. PMID- 27004691 TI - The response of claudin-like transmembrane septate junction proteins to altered environmental ion levels in the larval mosquito Aedes aegypti. AB - Septate junctions (SJs) occlude the paracellular pathway and function as paracellular diffusion barriers within invertebrate epithelia. However, integral components of SJs and their contribution to barrier properties have received considerably less attention than those of vertebrate occluding junctions. In arthropods, SJ proteins have only been identified in Drosophila and among these are three integral claudin-like proteins, Megatrachea (Mega), Sinuous (Sinu) and Kune-kune (Kune), as well as a receptor-like transmembrane SJ protein known as Neurexin IV (Nrx IV). In this study, mega, sinu, kune and nrx IV are identified and characterized in aquatic larvae of the mosquito Aedes aegypti and a role for these proteins in ionoregulatory homeostasis is considered. Transcripts encoding Mega, Sinu, Kune and Nrx IV were found in iono/osmoregulatory tissues such as the midgut, Malpighian tubules, hindgut and anal papillae, but abundance was greater in the hindgut and anal papillae. Using immunohistochemical and western blot analysis it was found that Kune localized to the regions of intercellular contact between epithelial cells of the rectum and posterior midgut and in the apical membrane domain of the syncytial epithelium of anal papillae. To investigate a potential role for integral SJ proteins in larval A. aegypti iono/osmoregulation, abundance was examined in animals reared in freshwater or brackish water (30 % seawater). In iono/osmoregulatory epithelia, larvae exhibited tissue-specific alterations in mega mRNA and Kune protein abundance, but not sinu or nrx IV mRNA. These studies provide a first look at the potential contribution of integral SJ components to iono/osmoregulatory homeostasis in an aquatic invertebrate. PMID- 27004693 TI - Histopathological Outcomes after Irreversible Electroporation for Prostate Cancer: Results of an Ablate and Resect Study. AB - PURPOSE: Irreversible electroporation is a tissue ablation modality that uses high voltage electric energy to induce an increase in cell membrane permeability. This causes destabilization of the existing cellular transmembrane potential leading to cell death, due to the inability to maintain cellular homeostasis. This phase I-II study was designed to evaluate the histopathological outcomes of irreversible electroporation to prostate and surrounding tissue in radical prostatectomy specimens. MATERIALS AND METHODS: Sixteen patients with prostate cancer underwent an irreversible electroporation ablation without curative intent, followed by radical prostatectomy scheduled 4 weeks later. For histopathological examination of the prostate, whole mounted tissue slices were examined by dedicated genitourinary pathologists. The borders of the ablation zone and residual tumor were outlined on the slides. RESULTS: The irreversible electroporation ablation zones were characterized as areas of fibrosis, necrosis and loss of epithelial tissue in terms of denudation in the glandular structures. The ablation zone was well demarcated, showing trenchant delineations between viable and nonviable tissue. The ablated tissue showed mild to moderate inflammation, with atrophic cells in 1 case. The area was surrounded by hemorrhage at the location of the electrodes. No skip lesions or viable tissue was seen in the ablation zone. Fibrinoid necrosis of the neurovascular bundle was observed in 13 patients and denudation of the urothelium of the prostatic urethra was seen in 9. CONCLUSIONS: Histopathological assessment of the prostate 4 weeks after irreversible electroporation ablation showed sharply demarcated fibrotic and necrotic tissue in the ablation zone. No viable tissue was observed in the irreversible electroporation ablation zone. PMID- 27004694 TI - High background in Luminex(r) assay for HLA antibody screening: Interest of Adsorb OutTM. AB - INTRODUCTION: The Luminex(r) technology has become an integral component of clinical decision-making and diagnosis of transplanted organ rejection. Despite the superior sensibility of this technology, it is not completely problem free. We have observed in these bead-based assays that sera of some patients give a high negative control bead (NC) value which makes assessing HLA antibodies difficult. Treatment of sera by the Adsorb OutTM reagent may reduce the high background. In this study, we want to evaluate the effect of the Adsorb OutTM on the NC's MFI value by comparing treated and untreated patients' sera. METHODS: HLA antibody screening was performed on 3011 sera. These sera came from patients awaiting and undergoing renal transplant from different Moroccan hospitals. The sera were analyzed using the standard protocol for Luminex(r) antibody screening. Sera with high NC's value has been pre-incubated by the Adsorb OutTM, and analyzed on Luminex(r). RESULTS: 3% of studied samples have high NC's value. The Adsorb OutTM decreases the NC's value and brings it back to a normal range in 62.2% treated sera. It has no effect in 12.3%. The Adsorb OutTM effect depends only of NC's value, independently to age, storage date, sex and immunization. CONCLUSION: The Adsorb OutTM reagent has an important effect in decreasing NC value of sera. However, it has no effect in some patient's sera. In these cases we could try another treatment, as EDTA, DTT. The non-specific binding may be caused by multiple patient-specific factors, it would be important to search correlation between them and NC's values. PMID- 27004696 TI - Erratum to: Markers of increased atherosclerotic risk in patients with chronic kidney disease: a preliminary study. PMID- 27004695 TI - Larvicidal and Pupicidal Activities of Alizarin Isolated from Roots of Rubia cordifolia Against Culex quinquefasciatus Say and Aedes aegypti (L.) (Diptera: Culicidae). AB - The mosquitocidal activities of different fractions and a compound alizarin from the methanol extract of Rubia cordifolia roots were evaluated on larvae and pupae of Culex quinquefasciatus Say and Aedes aegypti (L.) (Diptera: Culicidae). Larvae and pupae were exposed to concentrations of 2.5, 5.0, 7.5 and 10 ppm for fractions and 0.5, 1.0, 1.5 and 2.0 ppm for compound. After 24 h, the mortality was assessed and the LC50 and LC90 values were estimated for larvae and pupae. Among the 23 fractions screened, fraction 2 from the methanol extract of R. cordifolia showed good mosquitocidal activity against C. quinquefasciatus and A. aegypti. LC50 and LC90 values of fraction 2 were 3.53 and 7.26 ppm for C. quinquefasciatus and 3.86 and 8.28 ppm for A. aegypti larvae, and 3.76 and 7.50 ppm for C. quinquefasciatus and 3.92 and 8.05 ppm for A. aegypti pupae, respectively. Further, the isolated compound alizarin presented good larvicidal and pupicidal activities. LC50 and LC90 values of alizarin for larvae were 0.81 and 3.86 ppm against C. quinquefasciatus and 1.31 and 6.04 ppm for A. aegypti larvae, respectively. Similarly, the LC50 and LC90 values of alizarin for pupae were 1.97 and 4.79 ppm for C. quinquefasciatus and 2.05 and 5.59 ppm for A. aegypti pupae, respectively. The structure of the isolated compound was identified on the basis of spectroscopic analysis and compared with reported spectral data. The results indicated that alizarin could be used as a potential larvicide and pupicide. PMID- 27004697 TI - Halitosis, an imperative constraint in measuring the outcome of the oral care in oncology patients. PMID- 27004699 TI - Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis. AB - Mitochondria are multifunctional cellular organelles that host many biochemical pathways including oxidative phosphorylation (OXPHOS). Defective mitochondria pose a threat to cellular homeostasis and compensatory responses exist to curtail the source of stress and/or its consequences. The mitochondrial proteome comprises proteins encoded by the nuclear and mitochondrial genomes. Disturbances in protein homeostasis may originate from mistargeting of nuclear encoded mitochondrial proteins. Defective protein import and accumulation of mistargeted proteins leads to stress that triggers translation alterations and proteasomal activation. These cytosolic pathways are complementary to the mitochondrial unfolded protein response (UPRmt) that aims to increase the capacity of protein quality control mechanisms inside mitochondria. They constitute putative targets for interventions aimed at increasing the fitness, stress resistance, and longevity of cells and organisms. PMID- 27004698 TI - Microglia: Architects of the Developing Nervous System. AB - Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and refinement of neural circuits. Furthermore, we review studies suggesting that these cellular functions result in the modulation of behavior, which has important implications for a variety of neurological disorders. PMID- 27004700 TI - Neutrophil-to-lymphocyte ratio may be a marker of peripheral artery disease complexity. AB - OBJECTIVE: The aim of this study was to evaluate the relationship between peripheral artery disease (PAD) severity and complexity, as evaluated by TransAtlantic Inter-Society Consensus-II (TASC-II) classification, and neutrophil to-lymphocyte (N/L) ratio. METHODS: A total of 407 patients underwent peripheral angiography due to signs and symptoms of PAD; of these, 64 patients were excluded and the remaining 343 patients were WARFARIN in this cross-sectional study. Patients with previous peripheral revascularizations, acute coronary syndrome, vasculitis, non-atherosclerotic stenosis, and malignancy were excluded. Patients were divided into 4 groups according to TASC-II classification, and clinical and laboratory data were compared. The chi-square test, Student's t-test, Mann Whitney U test, analysis of variance, Kruskal-Wallis test, Spearman's correlation analysis, multiple logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. RESULTS: Lymphocyte count was weakly correlated (r=-0.169, p=0.002) whereas neutrophil count and N/L ratio were moderately correlated with the TASC score (r=0.432, p<0.001 and r=0.470, p<0.001, respectively). Low-density lipoprotein cholesterol [odds ratio (OR)=1.010, 95% confidence interval (CI) 95%=1.003-1.017, p=0.004], high-density lipoprotein cholesterol (OR=0.940, 95% CI=0.894-0.987, p=0.013), and N/L ratio (OR=1.914, 95% CI=1.515-2.418, p<0.001) were the independent factors for predicting a higher TASC class in multiple logistic regression analysis. The cut-off value of the N/L ratio for predicting TASC C&D class was >3.05 (sensitivity=75.0%, specificity=62.9%, area under the curve=0.678, 95% CI=0.688 0.784, p<0.001) in ROC curve analysis. CONCLUSION: The N/L ratio, a marker of inflammation, may be an important predictor of PAD complexity. Therefore, a simple blood count test may provide an important clue about the severity of PAD and risk stratification in patients presenting with intermittent claudication. Additional studies are required to confirm our findings. PMID- 27004701 TI - Neopterin and interleukin-6 as predictors of recurrent atrial fibrillation. AB - OBJECTIVE: Available evidence suggests that inflammation may be associated with atrial fibrillation (AF). This prospective and observational study aimed to assess whether plasma neopterin (NPT) and interleukin-6 (IL-6) levels before and after electrical cardioversion (CV) predict AF recurrence. METHODS: The study was designed as a prospective observational trial. Blood samples were collected (24 hours before, 24 h after CV, and 7 days after CV) in 60 patients with a dual chamber pacemakar and preserved left ventricular systolic function who underwent successful CV of persistent AF. All significant parameters associated with AF recurrence lasting >=30 min and detected by pacemaker data logs were evaluated in multivariate logistic regression analysis. Echocardiography was performed 7 days after CV in patients with sinus rhythm. The control group included 17 subjects without AF. RESULTS: The analysis included 51 patients who remained in sinus rhythm 7 days after CV. During 12 months of follow-up, AF recurred in 46 patients. Baseline IL-6 levels did not differ between the two groups, but baseline NPT levels were higher in the study group than in the control group (19+/-7 vs. 11+/-5 nmol/mL, p<0.001). NPT levels of >=14.6 nmol/L at baseline and >=13.3 nmol/L 7 days after CV separated the patients with AF recurrence from those without arrhythmia after CV. Only left atrial emptying fraction <38% was an independent predictor of AF recurrence (p=0.03), whereas NPT levels of >=13.3 nmol/L 7 days after CV showed borderline statistical significance (p=0.07). CONCLUSION: Increased NPT level was observed in patients with persistent AF. Neither baseline IL-6 and NPT levels nor their changes within 7 days after CV were predictive of AF recurrence. Further studies are needed to establish the prognostic significance of NPT in patients with AF. PMID- 27004702 TI - Effects of cinacalcet treatment on QT interval in hemodialysis patients. AB - OBJECTIVE: Cinacalcet is a calcimimetic drug that acts via calcium-sensing receptors (CaSRs) and increases the sensitivity of CaSRs on the parathyroid gland; thus, it lowers calcium and phosphorus levels as well as parathormone levels. Prolongation of the QT interval is recognized as a risk factor for the development of ventricular arrhythmias and sudden death. Patients with end-stage renal disease (ESRD) are sensitive for QT prolongation and torsade de pointes more than the normal population. In this study, we aimed to evaluate the effects of cinacalcet on the electrocardiogram (ECG), particularly changes in the QT interval, in patients with ESRD. METHODS: Thirty-seven patients (21 males and 16 females) undergoing maintenance hemodialysis for at least 12 months were included in this retrospective study. Patients receiving cardioactive and antiarrhythmic drugs and those having a history of any cardiac or cerebrovascular events, active malignancy, and infections were excluded. Baseline ECG measurements of patients were performed over the newest ECG measurements that were obtained within 1 month before initiating the cinacalcet treatment, and the ECG measurements of patients after the cinacalcet treatment were performed according to the most recent ECG that was taken within the last 1 week in the clinic. We recorded the heart rate and QT values of patients before and after treatment and then calculated the corrected QT values (QTc). The Statistical Package for the Social Sciences (SPSS) ver. 21.0 was used for statistical analysis. RESULTS: The mean age of patients was 52.24+/-14.49 years. Prolongation of QTc was statistically significant compared with the baseline QTc value (baseline: 396.62+/-42.04 msec; after treatment: 404.97+/-43.47 msec; p=0.031). We found a positive correlation between the prolongation of QTc and treatment dose of cinacalcet (p<0.005, r=0.560). CONCLUSION: Clinicians should be very careful for life threatening cardiac side effects while increasing the dose of cinacalcet treatment in hemodialysis patients who have a borderline or prolonged QTc interval. PMID- 27004703 TI - Effects of N-acetyl cysteine on renal functions evaluated by blood neutrophil gelatinase-associated lipocalin levels in geriatric patients undergoing coronary artery bypass grafting. AB - OBJECTIVE: Recent conflicting studies on the renal effects of N-acetyl cysteine (NAC) after cardiac surgery have been published. The aim of this study was to evaluate the renal effects of NAC using neutrophil gelatinase-associated lipocalin (NGAL) blood levels in elderly patients undergoing coronary artery bypass grafting (CABG). METHODS: This randomized, double-blinded, placebo controlled study was conducted among geriatric patients (>65 years) scheduled to undergo CABG. A total of 60 consecutive patients were randomly assigned to 2 groups. The first group received I.V. NAC (n=30) and the second group received placebo (n=30) at induction of anesthesia and then for 20 h. NGAL values were determined and conventional renal function tests were performed. Statistical analysis was performed using SPSS 17.0 (IL, Chicago, USA). A p value of <0.05 was considered statistically significant. RESULTS: Plasma creatinine levels at 24 h postoperatively were significantly higher in the placebo group than in the NAC group (1.41+/-0.63 vs. 1.13+/-0.35; p<0.05). The mean serum NGAL levels at 3 h postoperatively were higher in the placebo group than in the NAC group (104.94+/ 30.51 vs. 87.82+/-25.18; p<0.05). NGAL levels were similar between the groups at all other measurement time points. Plasma creatinine levels of >=1.5 mg/dL or >25% of the baseline value at any time during the study period were observed in 27% of patients in the NAC group and 37% of patients in the placebo group; the difference was statistically significant (p<0.05). CONCLUSION: In the present study, we found that I.V. NAC infusion in elderly patients undergoing CABG reduced the incidence of acute kidney injury as determined by blood NGAL and creatinine levels. PMID- 27004704 TI - The use of pre-test and post-test probability values as criteria before selecting patients to undergo coronary angiography in patients who have ischemic findings on myocardial perfusion scintigraphy. AB - OBJECTIVE: Myocardial perfusion scintigraphy (MPS) is a diagnostic test which is frequently used in the diagnosis of coronary heart disease (CHD). MPS is generally interpreted as ischemia present or absent; however, it has a power in predicting the disease, similar to other diagnostic tests. In this study, we aimed to assist in directing the high-risk patients to undergo coronary angiography (CA) primarily by evaluating patients without prior CHD history with pre-test and post-test probabilities. METHODS: The study was designed as a retrospective study. Between January 2008 and July 2011, 139 patients with positive MPS results and followed by CA recently (<6 months) were evaluated from patient files. Patients' pre-test probabilities based on the Diamond and Forrester method and the likelihood ratios that were obtained from the literature were used to calculate the patients' post exercise and post-MPS probabilities. Patients were evaluated in risk groups as low, intermediate, and high, and an ROC curve analysis was performed for the post-MPS probabilities. RESULTS: Coronary artery stenosis (CAS) was determined in 59 patients (42.4%). A significant difference was determined between the risk groups according to CAS, both for the pre-test and post-test probabilities (p<0.001, p=0.024). The ROC analysis provided a cut-off value of 80.4% for post- MPS probability in predicting CAS with 67.9% sensitivity and 77.8% specificity. CONCLUSION: When the post-MPS probability is >=80% in patients who have reversible perfusion defects on MPS, we suggest interpreting the MPS as "high probability positive" to improve the selection of true-positive patients to undergo CA, and these patients should be primarily recommended CA. PMID- 27004705 TI - Evaluation of the association between stroke/transient ischemic attack and atrial electromechanical delay in patients with paroxysmal atrial fibrillation. AB - OBJECTIVE: This study aimed to evaluate the association between the history of stroke/transient ischemic attack (TIA) and inter- and intra-atrial electromechanical delay (EMD) in patients with paroxysmal atrial fibrillation (PAF). METHODS: Patients diagnosed with PAF were included in this retrospective study. Patients who had a history of stroke or TIA were defined as the symptomatic group, whereas those who did not have such a history were defined as the asymptomatic group. On the basis of the transthoracic echocardiographic records, atrial electromechanical coupling (time interval from the onset of the P wave on the surface electrocardiogram to the beginning of the A' wave interval with tissue Doppler echocardiography) and intra- and interatrial EMD were measured. RESULTS: In this study, 160 patients were included, 52 of whom were symptomatic. While the intra-left atrial EMD was 68.2+/-6.1 ms in the symptomatic group, it was found to be 50.8+/-6.5 ms in the asymptomatic group (p<0.001). Interatrial EMD was 91.3+/-5.0 ms in the symptomatic group, whereas it was 71.5+/ 7.0 ms in the asymptomatic group (p<0.001). In multiple logistic regression analysis, intra-left atrial [odds ratio (OR): 1.417, 95% confidence interval (CI): 1.193-1.684, p<0.001] and interatrial EMDs (OR: 1.398, 95% CI: 1.177-1.661, p<0.001) were found to be independently associated with the presence of stroke/TIA. CONCLUSION: Prolonged inter- and intra-left atrial EMDs in patients with PAF is associated with stroke/TIA. Evaluating this parameter in addition to the CHA2DS2-VASc score in patients with PAF may be helpful in identifying patients who are at a high risk of stroke/TIA. PMID- 27004706 TI - Association between carotid intima-media thickness and presence of coronary artery disease in chronic obstructive pulmonary disease patients. AB - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a risk factor for cardiovascular disease (CVD). Carotid intima-media thickness (CIMT) is the sign of subclinical atherosclerosis. Therefore, the aim of this study was to evaluate whether CIMT measurement is related with significant coronary artery disease (CAD) in patients with COPD, similar to those without COPD. METHODS: One hundred and eight patients with previously diagnosed COPD and 78 patients without COPD who underwent coronary angiography (CAG) were enrolled in this prospective cross sectional study. Carotid artery ultrasonography was performed on all patients after coronary angiography by another operator who was blind to the CAG results. The patients were divided into four subgroups as follows: group 1: COPD (-) and CAD (-); group 2: COPD (-) and CAD (+); group 3: COPD (+) and CAD (+); and group 4: COPD (+) and CAD (-). Patients with previous coronary revascularization, carotid artery disease, and lung disease other than COPD were not enrolled in this study. The student's t-test, chi-square analysis, multiple logistic regression analysis, and receiver operating characteristic (ROC) curve were used for statistical analysis. RESULTS: CIMT was found to be highest in patients with both significant CAD and COPD (group 3) (p<0.05). Among the 108 COPD patients, the odds ratio associated with the CIMT >1.25 mm to predict CAD was 12.4. The area under the ROC curve for a cut-off value of 1.25 mm for CIMT to predict CAD in COPD patients was calculated as 0.913, with a sensitivity of 89.7% and specificity of 86.7%. CONCLUSION: CIMT has a predictive value for the presence of CAD in patients with COPD. Further studies are needed to validate our results. PMID- 27004707 TI - Evaluating functional capacity, and mortality effects in the presence of atrial electromechanical conduction delay in patients with systolic heart failure. AB - OBJECTIVE: Atrial functions are relatively suppressed in heart failure (HF). We aimed to investigate the associations of intra- and inter-atrial electromechanical conduction delay (EMCD) with functional class and mortality over a 12-month follow-up period. METHODS: The prospective study included 65 patients with systolic HF and 65 healthy subjects with normal sinus rhythm. Left ventricular (LV) systolic functions and left atrial (LA) dimensions and volumes were evaluated by transthoracic echocardiography. Tissue Doppler imaging (TDI) signals at the lateral border of the mitral annulus (lateral PA'), septal mitral annulus (septal PA'), and tricuspid annulus (tricuspid PA') were measured. Intra- and inter-atrial EMCD were calculated. RESULTS: Mitral inflow velocities were studied using pulsed-wave Doppler after placing the sample volume at the leaflets' tips. The peak early (E wave) and late (A wave) velocities were measured. The septal annular E/E' ratio was relatively higher and lateral, septal, and right ventricular S, E', and A' waves were significantly lower in the HF group than in the control group (12.49+/-6.03 - 7.16+/-1.75, pE/E' <0.0001). Intra-atrial EMCD was detected as 117.5 ms and inter-atrial EMCD as 127.5 ms in patients with prolonged atrial EMCD. A significant increase was found in prolonged intraand inter-atrial EMCD according to functional capacity increase (p=0.012 and p=0.031, respectively). The incidence of mortality was significantly higher in patients with prolonged atrial EMCD (p=0.025), and 5 patients in the HF group died during the study over the 12-month follow-up period. CONCLUSIONS: In this study, we found a relationship between prolonged atrial conduction time and increased functional class and mortality in patients with systolic HF. PMID- 27004708 TI - Fragmented QRS frequency in patients with cardiac syndrome X. AB - OBJECTIVE: Cardiac syndrome X (CSX) is characterised by typical exertional chest pain, a positive response to exercise testing, and a normal coronary angiography. The relationship of CSX with myocardial fibrosis and ischemia has been clearly demonstrated in previous studies. In addition, fragmented QRS (fQRS) has been reported in the literature as an indicator of myocardial fibrosis. The aim of this study was to investigate the frequency of fQRS in patients with CSX. METHODS: This prospective case-control study included 37 patients (CSX group) with typical complaints of angina, ischemia on an exercise test, and normal coronary arteries as detected by angiography and 47 patients (control group) with normal coronary arteries. Echocardiographic examinations were performed according to the recommendations of the American Society of Echocardiography. Continuous variables were expressed as mean+/-standard deviation (SD), and the qualitative variables were expressed as a percentage or ratio. Data were compared statistically with Shapiro-Wilk test, Student's t-test, Mann-Whitney U, chi square and Fisher exact test. RESULTS: There was no significant difference between the CRX and control groups with respect to basic characteristics such as age and sex. fQRS and the frequency of its presentation with stable angina pectoris at the clinic were significantly higher in the CSX group than in the control group (p values: 0.001 and <0.001, respectively). CONCLUSION: A close follow-up would be useful in CSX patients in whom fQRS is detected in an electrocardiogram (ECG) because of the association between fQRS and poor prognosis with respect to the prevention of late complications. We believe that the presence of fQRS in the ECG aids in the diagnosis of CSX in clinical practice and in the recognition of this group of patients. PMID- 27004709 TI - mRNA PGC-1alpha levels in blood samples reliably correlates with its myocardial expression: study in patients undergoing cardiac surgery. AB - OBJECTIVE: Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator that has been proposed to play a protective role in mouse models of cardiac ischemia and heart failure, suggesting that PGC-1alpha could be relevant as a prognostic marker. Our previous studies showed that the estimation of peripheral mRNA PGC-1alpha expression was feasible and that its induction correlated with the extent of myocardial necrosis and left ventricular remodeling in patients with myocardial infarction. In this study, we sought to determine if the myocardial and peripheral expressions of PGC-1alpha are well correlated and to analyze the variability of PGC-1alpha expression depending on the prevalence of some metabolic disorders. METHODS: This was a cohort of 35 consecutive stable heart failure patients with severe aortic stenosis who underwent an elective aortic valve replacement surgery. mRNA PGC 1alpha expression was simultaneously determined from myocardial biopsy specimens and blood samples obtained during surgery by quantitative PCR, and a correlation between samples was made using the Kappa index. Patients were divided into two groups according to the detection of baseline expression levels of PGC-1alpha in blood samples, and comparisons between both groups were made by chi-square test or unpaired Student's t-test as appropriate. RESULTS: Based on myocardial biopsies, we found that mRNA PGC-1alpha expression in blood samples showed a statistically significant correlation with myocardial expression (Kappa index 0.66, p<0.001). The presence of higher systemic PGC-1alpha expression was associated with a greater expression of some target genes such as silent information regulator 2 homolog-1 (x-fold expression in blood samples: 4.43+/ 5.22 vs. 1.09+/-0.14, p=0.044) and better antioxidant status in these patients (concentration of Trolox: 0.40+/-0.05 vs. 0.34+/-0.65, p=0.006). CONCLUSIONS: Most patients with higher peripheral expression also had increased myocardial expression, so we conclude that the non-invasive estimation of mRNA PGC-1alpha expression from blood samples provides a good approach of the constitutive status of the mitochondrial protection system regulated by PGC-1alpha and that this could be used as prognostic indicator in cardiovascular disease. PMID- 27004710 TI - Association between baseline cardiovascular mechanics and exercise capacity in patients with coronary artery disease. AB - OBJECTIVE: Functional capacity is one of the cardinal determinants of morbidity and mortality in patients with coronary artery disease (CAD). We hypothesized that baseline cardiovascular mechanics, including cardiac systolic and diastolic functions, arterial mechanics, and ventriculoarterial interaction, may play a role in predicting exercise capacity in patients with CAD. METHODS: Fifty consecutive patients with CAD who were referred to cardiac rehabilitation were prospectively included in the study. Patients with non-sinus rhythms or severe valvular disease were excluded. Full left ventricular pressure-volume loops were constructed and arterial mechanics was evaluated using echocardiographic and tonometric measurements. Cardiopulmonary exercise tests were performed to measure exercise capacity. RESULTS: Fifty patients were enrolled in the study. Ventriculo arterial coupling showed a moderate correlation with peak oxygen consumption (VO2) (r=0.410, p=0.04) in patients with reduced left ventricular ejection fraction (LVEF). Only left ventricular volume at 15 mm Hg (r=0.514, p<0.01) in diastolic parameters (stiffness constant, p=0.75; ventricular compliance, p=0.17) and arterial compliance (r=0.467, p=0.01) in arterial parameters [arterial elastance, p=0.27; systemic vascular resistance, p=0.45; augmentation pressure, p=0.85; augmentation index (AIx), p=0.63; heart rate-corrected AIx, p=0.68] emerged as significant factors correlated with peak VO2 in patients with normal LVEF. CONCLUSION: Comprehensive evaluation of resting cardiovascular mechanics can give clues about exercise-recruited reserves of the cardiovascular system. Optimization of ventriculo-arterial coupling in patients with reduced LVEF and arterial compliance in patients with normal LVEF should be the main target in patients with CAD and limited functional capacity. PMID- 27004711 TI - The awareness, efficacy, safety, and time in therapeutic range of warfarin in the Turkish population: WARFARIN-TR. AB - OBJECTIVE: The awareness, time in therapeutic range (TTR), and safety of warfarin therapy were investigated in the adult Turkish population. METHODS: This multicenter prospective study includes 4987 patients using warfarin and involved regular international normalized ratio (INR) monitoring between January 1, 2014 and December 31, 2014. TTR was calculated according to F.R. Roosendaal's algorithm. Awareness was evaluated based on the patients' knowledge of warfarin's affect and food-drug interactions. RESULTS: The mean TTR of patients was 49.52+/ 22.93%. The patients with hypertension (55.3%), coronary artery disease (23.2%), congestive heart failure (24.5%), or smoking habit (20.8%) had significantly lower TTR levels than the others. Of the total number of patients, 42.6% had a mechanical valve, 38.4% had non-valvular atrial fibrillation (AF), and 19% had other indications for warfarin. Patients with other indications had lower TTR levels than those with mechanical valve and non-valvular AF (p=0.018). Warfarin awareness decreased in higher age groups. The knowledge of warfarin's food-drug interactions was 55%. People with higher warfarin awareness had higher TTR levels. Patients with <=8 INR monitoring/year had lower TTR levels (46.4+/-25.3 vs. 51.1+/-21.3, respectively, p<0.001) and lower awareness (44.6% vs. 60.6%, p<0.001) than patients with >=8 INR monitoring/year. In this study, 20.1% of the patients had a bleeding event (major bleeding 15.8%, minor bleeding 84.2%) within a year. CONCLUSION: Both the mean TTR ratios and awareness of the Turkish population on warfarin therapy were found to be low. It was thought that low TTR levels of the Turkish population may be caused by the low awareness of warfarin, warfarin's food-drug interactions, and high rates of concomitant diseases. PMID- 27004712 TI - Subcutaneous defibrillator implantation in pediatric patients. AB - OBJECTIVE: Although sudden cardiac death is rare in children, an intracardiac defibrillator system is indicated in children with various types of cardiomyopathy, primary electrical diseases, and after surgical repair of congenital heart defects. The use of transvenous defibrillator lead systems is limited in pediatric patients because of a small body size and/or limited vascular access. Subcutaneous array leads combined with an abdominally placed generator can enable implantation. METHOD: This is a retrospective study of 13 patients who underwent subcutaneous defibrillator implantation between September 2010 and March 2015. The subcutaneous system was preferred because patients were not amenable to transvenous lead placement. RESULTS: The median patient age was 4.1 years, and the median patient weight was 12.1 kg. Diagnoses of patients were long-QT syndrome in 6, aborted cardiac arrest with left ventricular non compaction in 3, hypertrophic cardiomyopathy with sustained ventricular tachycardia in 3, and arrythmogenic right ventricular cardiomyopathy in 1. Revision of the subcutaneous lead was required in 5 patients 2-26 months after the implantation. Appropriate shocks were observed in three patients. Inappropriate shock and lead fractures were observed in one patient during the follow-up period. The failure of therapy was observed in one patient. There were no perioperative complications and no early or late deaths. CONCLUSION: Subcutaneous defibrillator systems are safe and effective in pediatric patients when the transvenous method is risky and contraindicated. Because the high growth rate in this population leads to lead failures, a close follow-up of this population is essential. PMID- 27004713 TI - Complex evaluation of left atrial dysfunction in patients with type 1 diabetes mellitus by three-dimensional speckle tracking echocardiography: results from the MAGYAR-Path Study. AB - OBJECTIVE: Changes in left atrial (LA) function can be observed in type 1 diabetes mellitus (T1DM). Three-dimensional (3-D) speckle tracking echocardiography (STE) seems to be a promising tool for volumetric and functional evaluation of LA. The objective of the present study was to compare 3DSTE-derived LA volumetric and strain parameters between T1DM patients and matched healthy controls. METHODS: This prospective study consists of 17 subcutaneous insulin pump-treated non-obese patients with T1DM (mean age: 33.5+/-8.2 years, 8 males). To exclude possible cardiovascular disease, patients with complaints of chest pain, dyspnea, or signs of cerebrovascular disease or peripheral artery disease were not included. Their results were compared with 20 age-matched and gender matched healthy controls (mean age: 36.9+/-11.0 years, 9 males). Independent sample Student t-test and Fisher's exact test were used for comparisons. Bland Altman method was used for evaluating intraobserver and interobserver correlations. RESULTS: Anemia and impaired renal function were not confirmed in T1DM patients. Calculated LA maximum and minimum volumes and LA volume before atrial contraction were significantly increased in T1DM patients. Total atrial stroke volume was increased (23.6+/-6.9 mL vs. 19.6+/-4.6 mL, p=0.04), whereas mean segmental circumferential peak strain was decreased (28.9%+/-11.4% vs. 37.3%+/-12.5%, p=0.04). Segmental basal longitudinal and area strains were increased, whereas segmental superior circumferential and area strains and midatrial 3-D strain were decreased in T1DM. CONCLUSION: Both 3DSTE-derived volumetric and strain analysis confirmed alterations in LA function, suggesting early LA remodeling in patients with T1DM. PMID- 27004715 TI - Resilience in rural left-behind middle school students in Yunyang county of the Three Gorges area in China: a prospective cohort study. AB - BACKGROUND: The number of left-behind children in China is gradually increasing. This study aimed to understand the mental health status and changes in resilience of rural, left-behind middle school students in Yunyang County of the Three Gorges area in China. METHODS: A prospective cohort study, including two follow up surveys, with a frequency of once every 6 months was conducted among middle school students in Yunyang County. A self-designed questionnaire was used to obtain socio-demographic factors of participants, the Mental Health Test (MHT) scale was used to assess their mental health statuses, and resilience levels were collected using Resilience Youth Development Module (RYDM) scale at baseline and at the first and second follow-up investigations. RESULTS: Of the 1401 students who completed the baseline survey, 1322 students were eligible for the cohort study, of whom 1160 were investigated in the first follow-up survey. Ultimately, 1101 students completed the 1-year cohort. The detection rate of mental health problems for middle school students in the rural Three Gorges area was 5.64 %, and there was no significant difference between left-behind students (LBS) and non-left-behind students (NLBS) (chi (2) = 1.056, P = 0.304). The detection rates of medium resilience rose gradually (Z = 4.185, P = 0.000), while that of high resilience declined gradually (Z = 4.192, P = 0.000) in the baseline, first and second follow-up investigations. There was no significant difference between LBS and NLBS in resilience level (P > 0.05). The average RYDM scores were 2.990, 2.926, 2.904 among LBS in the baseline, first and second follow-up investigation, respectively, and the effect of time on the average RYDM scores was significant (F = 14.873, P = 0.000). The average MHT scores in LBS were 41.54, 39.79, 38.84 in the baseline, first and second follow-up investigations, respectively, and the detection rates of students who had psychological problems increased gradually (Z = 4.651, P = 0.000). The simple correlation coefficients between the RYDM and MHT scores were-0.227,-0.158, and-0.204 in the baseline, first and second follow-up survey, respectively (P = 0.000). CONCLUSIONS: The detection rate of mental health problems for middle school students in the rural Three Gorges area is relatively low and most of the LBS in area have medium or high resilience. The mental health status of LBS positively correlated with their resilience levels. Resilience declined gradually as time went on, but further studies with longer follow-up durations are needed to confirm the variation of resilience. PMID- 27004714 TI - New depression diagnosis following prescription of codeine, hydrocodone or oxycodone. AB - PURPOSE: Longer duration of prescription opioid use is associated with risk of major depression after controlling for daily morphine equivalent dose and pain. It is not known if risk of depression varies as a function of the type of opioid prescribed. METHODS: A retrospective cohort design was used to model onset of new depression diagnosis among 11 462 Veterans Health Administration (VA) patients who were prescribed only codeine, only hydrocodone or only oxycodone for >30 days. Patients were free of prevalent opioid use and depression at baseline (2000 2001). Follow-up was 2002-2012. Propensity scores and weighting were used to balance covariates across opioid type. Cox-proportional hazard models were computed, using weighted data and additional adjustment for morphine equivalent dose (MED), duration of use, and pain after opioid initiation, to estimate the risk of new depression diagnosis among patients prescribed only codeine, only oxycodone vs. those prescribed only hydrocodone. RESULTS: After controlling for confounding, we observed that patients prescribed codeine, compared to hydrocodone, were significantly more likely to have a new depression diagnosis (HR = 1.27; 95%CI: 1.12-1.43). Oxycodone was significantly associated with onset of new depression diagnosis when exposure was modeled as total days exposed in post-hoc analysis, but not when exposure was duration of incident period of use. CONCLUSIONS: Although codeine is a less potent opioid, after controlling for MED, chronic use of this agent is associated with nearly a 30% greater risk of depression compared to hydrocodone. Additional research is needed to determine the mechanisms for this association. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27004717 TI - Flow cytometry analysis of the microbiota associated with the midguts of vector mosquitoes. AB - BACKGROUND: The scientific interest to understand the function and structure of the microbiota associated with the midgut of mosquito disease vectors is increasing. The advancement of such a knowledge has encountered challenges and limitations associated with conventional culture-based and PCR techniques. METHODS: Flow cytometry (FCM) combined with various cell marking dyes have been successfully applied in the field of ecological microbiology to circumvent the above shortcomings. Here, we describe FCM technique coupled with live/dead differential staining dyes SYBR Green I (SGI) and Propidium Iodide (PI) to quantify and study other essential characteristics of the mosquito gut microbiota. RESULTS: A clear discrimination between cells and debris, as well as between live and dead cells was achieved when the midgut homogenate was subjected to staining with 5 * 103 dilution of the SGI and 30 MUM concentration of the PI. Reproducibly, FCM event collections produced discrete populations including non fluorescent cells, SYBR positive cells, PI fluorescing cells and cells that fluoresce both in SYBR and PI, all these cell populations representing, respectively, background noise, live bacterial, dead cells and inactive cells with partial permeability to PI. The FCM produced a strong linear relationship between cell counts and their corresponding dilution factors (R (2) = 0.987), and the technique has a better precision compared to qRT-PCR. The FCM count of the microbiota reached a peak load at 18 h post-feeding and started declining at 24 h. The present FCM technique also successfully applied to quantify bacterial cells in fixed midgut samples that were homogenized in 4 % PFA. CONCLUSION: The FCM technique described here offers enormous potential and possibilities of integration with advanced molecular biochemical techniques for the study of the microbiota community in disease vector mosquitoes. PMID- 27004718 TI - A 6-year Follow-up survey of health status in middle-aged women with Turner syndrome. AB - OBJECTIVE: Studies suggest younger women with Turner syndrome (TS) have good quality of life. Less is known about everyday functioning in adults with TS. In a 6-year follow-up study, multiple areas of functioning were compared between TS women and controls. DESIGN: Women with TS and controls were mailed a self-report survey 6 years after a baseline study. PATIENTS: Fifty-seven women with TS (M age 40.6 +/- 11.1 years) and 101 controls (M age 38.8 +/- 10.6 years, ns) responded. MEASUREMENTS: Measures of background information, experienced life strain and presence/impact of health conditions were developed for this study. The QPS Nordic measured perceived workload challenges. The LiSat-9 measured life satisfaction. The Rosenberg Self-Esteem Scale measured self-esteem. RESULTS: More TS women lived alone, fewer had biological children, and more had adoptive children. TS women reported fewer sex partners and less sexual confidence. Controls had higher education. There was no difference in employment status. More TS women received disability pensions. TS women reported their work as more physically challenging, less positively challenging and requiring less knowledge skills. TS women experienced more life strain in school, adolescence and late working life. Controls reported higher overall life satisfaction, with no difference between samples on specific domains. TS women reported lower self esteem. For TS women only, physical health at baseline predicted length of education and mental health at baseline predicted self-esteem. CONCLUSIONS: Women with TS face more challenges than controls on several domains of functioning. Early physical and mental health may influence later educational achievement and self-esteem for women with TS. PMID- 27004719 TI - Smartwatches as chest compression feedback devices: A feasibility study. AB - BACKGROUND: Recently, there have been attempts to use smartphones and smartwatches as the feedback devices to improve the quality of chest compressions. In this study, we compared chest compression depth feedback accuracy between a smartphone and a smartwatch in a hands-only cardiopulmonary resuscitation scenario, using a manikin with a displacement sensor system. METHODS: Ten basic life support providers participated in this study. Guided by the chest compression depths displayed on the monitor of a laptop, which received data from the manikin, each participant performed 2min of chest compressions for each target depth (35mm and 55mm) on a manikin while gripping a smartphone and wearing a smartwatch. Participants had a rest of 1h between the instances, and the first target depth was set at random. Each chest compression depth data value from the smartphone and smartwatch and a corresponding reference value from the manikin with the displacement system were recorded. To compare the accuracy between the smartphone and smartwatch, the errors, expressed as the absolute of the differences between the reference and each device, were calculated. RESULTS: At both target depths, the error of the smartwatch were significantly smaller than that of the smartphone (the errors of the smartphone vs. smartwatch at 35mm: 3.4 (1.3) vs. 2.1 (0.8) mm; p=0.008; at 55mm: 5.3 (2.8) vs. 2.3 (0.9) mm; p=0.023). CONCLUSION: The smartwatch-based chest compression depth feedback was more accurate than smartphone-based feedback. PMID- 27004720 TI - Outcomes of Primary Endodontic Therapy Provided by Endodontic Specialists Compared with Other Providers. AB - INTRODUCTION: The objective of this study was to compare the outcomes of initial nonsurgical root canal therapy for different tooth types provided by both endodontists and other providers. METHODS: By using an insurance company database, 487,476 initial nonsurgical root canal therapy procedures were followed from the time of treatment to the presence of an untoward event indicated by Current Dental Terminology codes for retreatment, apical surgery, or extraction. Population demographics were computed for provider type and tooth location. Kaplan-Meier survival estimates were calculated for 1, 5, and 10 years. Hazard ratios for provider type and tooth location were calculated by using the Cox proportional hazards model. RESULTS: The survival of all teeth collectively was 98% at 1 year, 92% at 5 years, and 86% at 10 years. Significant differences in survival on the basis of provider type were noted for molars at 5 years and for all tooth types at 10 years. The greatest difference discovered was 5% higher survival rate at 10 years for molars treated by endodontists. A hazard ratio of 1.394 was found when comparing other providers' success with that of endodontists within this 10-year molar group. CONCLUSIONS: These findings show that survival rates of endodontically treated teeth are high at 10 years after treatment regardless of provider type. Molars treated by endodontists after 10 years have significantly higher survival rates than molars treated by non-endodontists. PMID- 27004716 TI - Pathway analysis in attention deficit hyperactivity disorder: An ensemble approach. AB - Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. (c) 2016 Wiley Periodicals, Inc. PMID- 27004721 TI - Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review. AB - BACKGROUND: There is an increasing number of meta-analyses including data from non-randomized studies for therapeutic evaluation. We aimed to systematically assess the methods used in meta-analyses including non-randomized studies evaluating therapeutic interventions. METHODS: For this methodological review, we searched MEDLINE via PubMed, from January 1, 2013 to December 31, 2013 for meta analyses including at least one non-randomized study evaluating therapeutic interventions. Etiological assessments and meta-analyses with no comparison group were excluded. Two reviewers independently assessed the general characteristics and key methodological components of the systematic review process and meta analysis methods. RESULTS: One hundred eighty eight meta-analyses were selected: 119 included both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) and 69 only NRSI. Half of the meta-analyses (n = 92, 49%) evaluated non-pharmacological interventions. "Grey literature" was searched for 72 meta-analyses (38%). An assessment of methodological quality or risk of bias was reported in 135 meta-analyses (72%) but this assessment considered the risk of confounding bias in only 33 meta-analyses (18%). In 130 meta-analyses (69%), the design of each NRSI was not clearly specified. In 131 (70%), whether crude or adjusted estimates of treatment effect for NRSI were combined was unclear or not reported. Heterogeneity across studies was assessed in 182 meta-analyses (97%) and further explored in 157 (84%). Reporting bias was assessed in 127 (68%). CONCLUSIONS: Some key methodological components of the systematic review process search for grey literature, description of the type of NRSI included, assessment of risk of confounding bias and reporting of whether crude or adjusted estimates were combined-are not adequately carried out or reported in meta-analyses including NRSI. PMID- 27004722 TI - Routine prophylaxis with proton pump inhibitors and post-transplant complications in kidney transplant recipients undergoing early corticosteroid withdrawal. AB - Surgical stress, corticosteroids, and mycophenolate may contribute to gastrointestinal ulcers/bleeding after kidney transplantation. Prophylactic acid suppression with H2RAs or PPIs is often utilized after transplantation, although unclear if truly indicated after early corticosteroid withdrawal (CSWD). PPIs have been associated with increased risks of Clostridium difficile infection (CDI), pneumonia, and acute rejection. This retrospective cohort study investigated benefits and risks of prolonged PPI use following kidney transplantation and included 286 kidney recipients undergoing CSWD within five d of transplant who were maintained on tacrolimus and mycophenolate mofetil/sodium. Patients on PPI before transplant, H2RA before/after transplant, and/or those with pre-transplant GI complications were excluded. A total of 171 patients received PPI>30 d, mean duration 287 +/- 120 d (PPI group); 115 patients were not maintained on acid suppression (No-PPI group). GI ulceration and bleeding events were rare in PPI group (1.2% and 2.3%, respectively) and not observed in No-PPI group (p = NS). The incidence of infectious or hematological complications was not significantly different between groups. The PPI group experienced more biopsy proven acute rejection (9.4% vs. 2.6%, p = 0.03). No direct benefit was observed with PPI in reducing the incidence of GI ulcers and bleeding events in kidney transplant recipients undergoing early CSWD. Further studies are needed to investigate the association of PPI and acute rejection. PMID- 27004723 TI - Epidemiologic evidence of slow growing, nonprogressive or regressive breast cancer: A systematic review. AB - The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC. PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis. Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In three controlled cohort studies (diagnoses 1978 2006), the 5-years overall survival was 19-43%. Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2-14.7%. Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared with nonscreened BC was estimated as 1.2 and 1.1. It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies. PMID- 27004724 TI - Two new eunicellin diterpenoids from the East China Sea gorgonian Muricella sp. AB - A phytochemical investigation on gorgonian Muricella sp. from East China Sea resulted in the isolation of eight eunicellin diterpenoids including two new ones, muricellins A-B (1, 2). Chemical structures of these compounds were elucidated by spectroscopic techniques (1D and 2D NMR and MS) and by comparison with data reported in the literature. Anti-rheumatoid arthritis activities of 1, 3, 4, and 6 have been evaluated. PMID- 27004725 TI - Obstetrician Attitudes, Experience, and Knowledge of Planned Home Birth: An Exploratory Study. AB - BACKGROUND: The incidence of planned home birth is increasing in the United States. The American College of Obstetricians and Gynecologists acknowledges a woman's right to make an informed choice about place of delivery, including home birth. This exploratory study measures obstetricians' attitudes, experiences, and knowledge about planned home birth, identifies associations between these factors, and compares obstetricians' responses in Ohio to those in Arizona and New Mexico. METHODS: A survey about attitudes, experiences, and knowledge of planned home birth was distributed to obstetricians in Ohio, Arizona, and New Mexico. Attitude and knowledge scores were calculated for each respondent and used to evaluate associations through linear regression. Attitude and knowledge scores in states that have regulation of direct entry midwives (Arizona and New Mexico) were compared to a state which does not (Ohio). RESULTS: Obstetricians in all three states reported little experience and knowledge of planned home birth and overall negative attitudes. Obstetricians with stronger knowledge did not differ in their attitudes from those with less knowledge. No statistically significant differences were found when comparing attitude and knowledge scores in Ohio to Arizona and New Mexico, but Ohio obstetricians responded most negatively to the attitude questions. CONCLUSIONS: Obstetricians have limited knowledge and experience and hold very negative attitudes about planned home birth. Research is necessary to determine: 1) whether negative obstetrician attitudes would be modified by exposure to home birth education and experience, and, 2) whether negative obstetrician beliefs deter safe and timely transfer from home or compromise hospital care for transferred parturients. PMID- 27004726 TI - A new trial design to accelerate tuberculosis drug development: the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP). AB - BACKGROUND: The standard 6-month four-drug regimen for the treatment of drug sensitive tuberculosis has remained unchanged for decades and is inadequate to control the epidemic. Shorter, simpler regimens are urgently needed to defeat what is now the world's greatest infectious disease killer. METHODS: We describe the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP) as a novel hybrid phase II/III trial design to accelerate regimen development. In the Phase IIC STEP trial, the experimental regimen is given for the duration for which it will be studied in phase III (presently 3 or 4 months) and patients are followed for clinical outcomes of treatment failure and relapse for a total of 12 months from randomisation. Operating characteristics of the trial design are explored assuming a classical frequentist framework as well as a Bayesian framework with flat and sceptical priors. A simulation study is conducted using data from the RIFAQUIN phase III trial to illustrate how such a design could be used in practice. RESULTS: With 80 patients per arm, and two (2.5 %) unfavourable outcomes in the STEP trial, there is a probability of 0.99 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.91 that the proportion of unfavourable outcomes would be less than 8 %. With six (7.5 %) unfavourable outcomes, there is a probability of 0.82 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.41 that it would be less than 8 %. Simulations using data from the RIFAQUIN trial show that a STEP trial with 80 patients per arm would have correctly shown that the Inferior Regimen should not proceed to phase III and would have had a high chance (0.88) of either showing that the Successful Regimen could proceed to phase III or that it might require further optimisation. CONCLUSIONS: Collection of definitive clinical outcome data in a relatively small number of participants over only 12 months provides valuable information about the likelihood of success in a future phase III trial. We strongly believe that the STEP trial design described herein is an important tool that would allow for more informed decision-making and accelerate regimen development. PMID- 27004727 TI - Analysis and critical comparison of food allergen recalls from the European Union, USA, Canada, Hong Kong, Australia and New Zealand. AB - As part of a European Union-funded project (FP7) developing 'Integrated approaches to food allergen and allergy management', a database was constructed based on publicly available information on food allergen recalls in Europe, North America, Hong Kong, Australia and New Zealand. Over 2000 entries were made into the database. The database covers a 4-year period from 2011 to 2014 and each entry is categorised into food type (two different classifications), identified allergen and cause where indicated by the authorities. Across different authorities, by far the biggest incidence of undeclared allergens occurred in the food categories of prepared dishes and snacks (range = 12-53%), and cereals and bakery products (range = 14-25% of all recalls and/or alerts). The biggest incidence of undeclared allergens, according to the information from most authorities, occurred for milk and milk products (16-31% of all products with recall or alert), followed by cereals containing gluten (9-19%), soy (5-45%), and egg and egg products (5-17%). Although 42-90% of the products with recalls/alerts were explained as being 'Not indicated on the label', this is a generic explanation of cause and does not provide much insight into the causes of the recall/alerts. However, 0-17% of products with recalls/alerts could be coded as caused by the unintended presence of an allergen as the probable result of cross contact in production. Construction of the database of allergen recalls has provided some important lessons and recommendations to the authorities are made in this paper in terms of the harmonisation of the reporting of allergen recalls into a more standardised format. PMID- 27004728 TI - Oncoplastic breast reconstruction: Patient selection and surgical techniques. AB - Standard breast conserving techniques often fail to achieve the desired goal of tumor extirpation with adequate margins while preserving breast cosmesis. The emergence of oncoplastic breast reconstruction addresses these limitations and also allows breast conservation in women who would not have met traditional criteria. Using various volume displacing oncoplastic techniques, tumors can be successfully resected from any quadrant of the breast, while maintaining or improved breast cosmesis, diminishing post-radiation deformities, and providing breast symmetry. J. Surg. Oncol. 2016;113:875-882. (c) 2016 Wiley Periodicals, Inc. PMID- 27004730 TI - Addressing HIV risk behaviour in South Africa: Yes, HIV testing in treatment centres in important, but far more is needed. PMID- 27004729 TI - Compensatory activation in fronto-parietal cortices among HIV-infected persons during a monetary decision-making task. AB - HIV infection can cause direct and indirect damage to the brain and is consistently associated with neurocognitive disorders, including impairments in decision-making capacities. The tendency to devalue rewards that are delayed (temporal discounting) is relevant to a range of health risk behaviors. Making choices about delayed rewards engages the executive control network of the brain, which has been found to be affected by HIV. In this case-control study of 18 HIV positive and 17 HIV-negative adults, we examined the effects of HIV on brain activation during a temporal discounting task. Functional MRI (fMRI) data were collected while participants made choices between smaller, sooner rewards and larger, delayed rewards. Choices were individualized based on participants' unique discount functions, so each participant experienced hard (similarly valued), easy (disparately valued), and control choices. fMRI data were analyzed using a mixed-effects model to identify group-related differences associated with choice difficulty. While there was no difference between groups in behavioral performance, the HIV-positive group demonstrated significantly larger increases in activation within left parietal regions and bilateral prefrontal regions during easy trials and within the right prefrontal cortex and anterior cingulate during hard trials. Increasing activation within the prefrontal regions was associated with lower nadir CD4 cell count and risk-taking propensity. These results support the hypothesis that HIV infection can alter brain functioning in regions that support decision making, providing further evidence for HIV associated compensatory activation within fronto-parietal cortices. A history of immunosuppression may contribute to these brain changes. Hum Brain Mapp 37:2455 2467, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004731 TI - Synthesis of 2-Benzylphenyl Ketones by Aryne Insertion into Unactivated C-C Bonds. AB - A transition-metal-free procedure to access to functionalized 2-benzylphenyl ketones is described by direct insertion of arynes into benzylic C-C bonds. This reaction was promoted by cesium fluoride at room temperature, allowing the products to form in high selectivity and achieve good functional group tolerance. PMID- 27004733 TI - 2-Hydroxyisocaproic acid is bactericidal in human dental root canals ex vivo. AB - AIM: To compare the activity of 2-hydroxyisocaproic acid (HICA), calcium hydroxide (Ca(OH)2 ) and chlorhexidine digluconate (CHG) against Enterococcus faecalis T-75359 (root canal isolate) in the root canals of extracted human teeth. METHODOLOGY: Bacterial suspensions (108 cfu mL-1 ) were incubated in root canals with 0.9 mm diameter root blocks (n = 73) for 21 days. Bacterial penetration into dentine was analysed by the Brown and Brenn method (n = 5). Canals (n = 17/group) were medicated with 40% of HICA paste, 40% of Ca(OH)2 paste, 2% of CHG solution or 0.9% of saline solution for 7 days. Samples taken from the inner (first 0.1 mm) and deeper (second 0.1 mm) dentine, and residual roots were cultured in broth for 24 h. Bacterial growth was detected by spectrophotometry (optical density, OD) and confirmed by culture on agar. The OD data were analysed with Kruskal-Wallis and Friedman with Wilcoxon signed-rank test between and within groups, respectively, and agar culture data with Pearson chi-square with Mann-Whitney and Cochran with McNemar tests, respectively (P < 0.05). RESULTS: Bacterial invasion into dentine tubules was confirmed. In deeper dentine, HICA inhibited >90% of bacterial growth in comparison with saline. No bacterial growth was observed in 82-100% of inner and deeper dentine samples. CHG prevented the growth in 88%, Ca(OH)2 in 59-76% and saline in 65-71%, respectively. HICA was significantly more active than Ca(OH)2 (P = 0.008) in the residual roots. The viability testing on agar showed essentially the same result. CONCLUSION: HICA paste exerted superior activity against E. faecalis and could have potential for root canal medication. PMID- 27004734 TI - A DFT-based comparative equilibrium study of thermal dehydration and hydrolysis of CaCl2 hydrates and MgCl2 hydrates for seasonal heat storage. AB - Salt hydrates store solar energy in chemical form via a reversible dehydration hydration reaction. However, as a side reaction to dehydration, hydrolysis (HCl formation) may occur in chloride based salt hydrates (specially in MgCl2 hydrates), affecting the durability of the storage system. The mixture of CaCl2 and MgCl2 hydrates has been shown experimentally to have exceptional cycle stability and improved kinetics. However, the optimal operating conditions for the mixture are unknown. To understand the appropriate balance between dehydration and hydrolysis kinetics in the mixtures, it is essential to gain in depth insight into the mixture components. We present a GGA-DFT level study to investigate the various gaseous structures of CaCl2 hydrates and to understand the relative stability of their conformers. The hydration strength and relative stability of conformers are dominated by electrostatic interactions. A wide network of intramolecular homonuclear and heteronuclear hydrogen bonds is observed in CaCl2 hydrates. Equilibrium product concentrations are obtained during dehydration and hydrolysis reactions under various temperature and pressure conditions. The trend of the dehydration curve with temperature in CaCl2 hydrates is similar to the experiments. Comparing these results to those of MgCl2 hydrates, we find that CaCl2 hydrates are more resistant towards hydrolysis in the temperature range of 273-800 K. Specifically, the present study reveals that the onset temperatures of HCl formation, a crucial design parameter for MgCl2 hydrates, are lower than for CaCl2 hydrates except for the mono-hydrate. PMID- 27004732 TI - Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: To evaluate the effectiveness of antipsychotic medications in preventing and treating delirium. DESIGN: Systematic review and meta-analysis. SETTING: PubMed, EMBASE, CINAHL, and ClinicalTrials.gov databases were searched from January 1, 1988, to November 26, 2013. PARTICIPANTS: Adult surgical and medical inpatients. INTERVENTION: Antipsychotic administration for delirium prevention or treatment in randomized controlled trials or cohort studies. MEASUREMENTS: Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. Heterogeneity was considered as chi-square P < .1 or I(2) > 50%. Using a random-effects model (I(2) > 50%) or a fixed-effects model (I(2) < 50%), odds ratios (ORs) were calculated for dichotomous outcomes (delirium incidence and mortality), and mean or standardized mean difference for continuous outcomes (delirium duration, severity, hospital and intensive care unit (ICU) length of stay (LOS)). Sensitivity analyses included postoperative prevention studies only, exclusion of studies with high risk of bias, and typical versus atypical antipsychotics. RESULTS: Screening of 10,877 eligible records identified 19 studies. In seven studies comparing antipsychotics with placebo or no treatment for delirium prevention after surgery, there was no significant effect on delirium incidence (OR = 0.56, 95% confidence interval (CI) = 0.23-1.34, I(2) = 93%). Using data reported from all 19 studies, antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU LOS, with high heterogeneity among studies. No association with mortality was detected (OR = 0.90, 95% CI = 0.62-1.29, I(2) = 0%). CONCLUSION: Current evidence does not support the use of antipsychotics for prevention or treatment of delirium. Additional methodologically rigorous studies using standardized outcome measures are needed. PMID- 27004735 TI - Immunochip analysis identifies association of the RAD50/IL13 region with human longevity. AB - Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip = 7.01 * 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip < 5 * 10(-4) for replication in two samples from France (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl = 5.42 * 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life. PMID- 27004736 TI - Health and happiness among community-dwelling older adults in Domkhar valley, Ladakh, India. AB - AIM: The aim of the present study was to show the status of objective geriatric functions and subjective quality of life in Ladakh, India, compared with Japanese controls. METHODS: We analyzed data of 117 people aged 60 years or older in Domkhar, and age- and sex-specific Japanese controls. Variables measured included blood pressure, hemoglobin, timed up & go test, basic activities of daily living, Geriatric Depression Scale and the Visual Analog Scale for subjective quality of life. RESULTS: People in Domkhar were more likely to have difficulties in basic activities of daily living compared with Japanese controls. However, they were significantly more likely to maintain social roles. The Visual Analog Scale scores in subjective friendship, economic satisfaction and happiness were higher in Domkhar compared with Japanese controls. Living alone (OR 9.92, 95% CI 2.13 46.26), high Geriatric Depression Scale score (6 or more; OR 8.45, 95% CI 1.65 43.35) and timed up & go test (17 s or more; OR 21.00, 95% CI 1.69-260.87) were significantly associated with a low score of subjective happiness (less than 50). Residence in Domkhar (OR 0.17, 95% CI 0.04-0.77) was a significant factor for low prevalence of a low score of subjective happiness by multivariate logistic regression analysis. CONCLUSIONS: Subjective quality of life among older adults in Domkhar was higher than Japanese controls despite a higher rate of difficulty in basic activities of daily living. We have to consider prevention, treatment, and care of not only diseases and disabilities, but also loneliness for the older adults. Geriatr Gerontol Int 2017; 17: 480-486. PMID- 27004737 TI - alpha-Galactosylceramide protects swine against influenza infection when administered as a vaccine adjuvant. AB - Natural killer T (NKT) -cells activated with the glycolipid ligand alpha galactosylceramide (alpha-GalCer) stimulate a wide array of immune responses with many promising immunotherapeutic applications, including the enhancement of vaccines against infectious diseases and cancer. In the current study, we evaluated whether alpha-GalCer generates protective immunity against a swine influenza (SI) virus infection when applied as an intramuscular vaccine adjuvant. Immunization of newly weaned piglets with UV-killed pandemic H1N1 A/California/04/2009 (kCA04) SI virus and alpha-GalCer induced high titers of anti-hemagglutinin antibodies and generated virus-specific T cells that localized in intrapulmonary airways and in alveolar walls. Vaccination with alpha-GalCer resulted in a systemic increase in NKT-cell concentrations, including in the respiratory tract, which was associated with complete inhibition of viral replication in the upper and lower respiratory tract and much reduced viral shedding. These results indicate that NKT-cell agonists could be used to improve swine vaccine formulations in order to reduce the clinical signs of SI infection and limit the spread of influenza viruses amongst commercial pigs. PMID- 27004738 TI - Solvent-surface interactions control the phase structure in laser-generated iron gold core-shell nanoparticles. AB - This work highlights a strategy for the one-step synthesis of FeAu nanoparticles by the pulsed laser ablation of alloy targets in the presence of different solvents. This method allows particle generation without the use of additional chemicals; hence, solvent-metal interactions could be studied without cross effects from organic surface ligands. A detailed analysis of generated particles via transmission electron microscopy in combination with EDX elemental mapping could conclusively verify that the nature of the used solvent governs the internal phase structure of the formed nanoparticles. In the presence of acetone or methyl methacrylate, a gold shell covering a non-oxidized iron core was formed, whereas in aqueous media, an Au core with an Fe3O4 shell was generated. This core-shell morphology was the predominant species found in >90% of the examined nanoparticles. These findings indicate that fundamental chemical interactions between the nanoparticle surface and the solvent significantly contribute to phase segregation and elemental distribution in FeAu nanoparticles. A consecutive analysis of resulting Fe@Au core-shell nanoparticles revealed outstanding oxidation resistance and fair magnetic and optical properties. In particular, the combination of these features with high stability magnetism and plasmonics may create new opportunities for this hybrid material in imaging applications. PMID- 27004739 TI - Predictive Effects of Lung function test on Postoperative Pneumonia in Squamous Esophageal Cancer. AB - Pulmonary function tests had prospective implications for postoperative pneumonia, which occurred frequently after esophagectomy. Understanding factors that were associated with pulmonary infection may help in patient selection and postoperative management. We performed a retrospective review of 2 independent cohorts including 216 patients who underwent esophagectomy between November 2011 and May 2014, aiming at identifying predictors of primary pneumonia. Univariate analysis was used to identify potential covariates for the development of primary pneumonia. Adjustments for multiple comparisons were made using False Discovery Rate (FDR) (Holm-Bonferroni method). Multivariable logistic regression analysis was used to identify independent predictors and construct a regression model based on a training cohort (n = 166) and then the regression model was validated using an independent cohort (n = 50). It showed that low PEF (hazard ratio 0.97, P = 0.009) was independent risk factors for the development of primary pneumonia in multivariate analyses and had a predictive effect for primary pneumonia (AUC = 0.691 and 0.851 for training and validation data set, respectively). Therefore, PEF has clinical value in predicting postoperative pneumonia after esophagectomy and it may serve as an indicator of preoperative lung function training. PMID- 27004740 TI - Catalyst free visible light induced cycloaddition as an avenue for polymer ligation. AB - The current study introduces a tetrazole species able to perform a rapid, visible light induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC). Full conversion of the tetrazole species under mild, catalyst free conditions is reported. Importantly, the visible light ligation technology is applied as a method for the modification and ligation of polymers featuring the rapid, clean and exclusive formation of the desired cycloadduct. PMID- 27004742 TI - Duties to rescue: individual, professional and institutional. PMID- 27004744 TI - A beacon for free healthcare in Pakistan. PMID- 27004741 TI - The Periosteal Bone Surface is Less Mechano-Responsive than the Endocortical. AB - Dynamic processes modify bone micro-structure to adapt to external loading and avoid mechanical failure. Age-related cortical bone loss is thought to occur because of increased endocortical resorption and reduced periosteal formation. Differences in the (re)modeling response to loading on both surfaces, however, are poorly understood. Combining in-vivo tibial loading, in-vivo micro-tomography and finite element analysis, remodeling in C57Bl/6J mice of three ages (10, 26, 78 week old) was analyzed to identify differences in mechano-responsiveness and its age-related change on the two cortical surfaces. Mechanical stimulation enhanced endocortical and periosteal formation and reduced endocortical resorption; a reduction in periosteal resorption was hardly possible since it was low, even without additional loading. Endocortically a greater mechano responsiveness was identified, evident by a larger bone-forming surface and enhanced thickness of formed bone packets, which was not detected periosteally. Endocortical mechano-responsiveness was better conserved with age, since here adaptive response declined continuously with aging, whereas periosteally the main decay in formation response occurred already before adulthood. Higher endocortical mechano-responsiveness is not due to higher endocortical strains. Although it is clear structural adaptation varies between different bones in the skeleton, this study demonstrates that adaptation varies even at different sites within the same bone. PMID- 27004745 TI - Impact on a Person's Daily Life During Episodes of Supraventricular Tachycardia. AB - PURPOSE: To describe the impact of episodes of supraventricular tachycardia (SVT) on a person's daily life from a holistic perspective. METHOD: A deductive descriptive design was used. Twenty semistructured interviews (12 women and 8 men) were conducted before planned ablation of SVT and were analyzed using qualitative content analysis. RESULTS: Living with SVT had a complex impact on daily life. Initially, the patients described an inhibited existence due to demands to give up things that they had previously been doing, in case the unpredictable episodes of SVT would occur. The episodes caused fatigue and worry, which together created a barrier for living life to the full by making the person give up undertakings. The patients constantly needed to find short-term and long term strategies to prevent new episodes from happening. CONCLUSION: Episodes of SVT entail a complex life situation as the person's entire existence is affected in daily life. To understand the impact of SVT on daily life, nurses and other health care professionals need increased knowledge and understanding to be able to provide support through relevant information and take optimal care measures. PMID- 27004746 TI - Phosphorene under electron beam: from monolayer to one-dimensional chains. AB - Phosphorene, a single sheet of black phosphorus, is an elemental two-dimensional material with unique properties and potential applications in semiconductor technology. While few-layer flakes of the material have been characterized using transmission electron microscopy, very little is known about its response to electron irradiation, which may be particularly important in the context of top down engineering of phosphorus nanostructures using a focused electron beam. Here, using first-principles simulations, we study the production of defects in a single phosphorene sheet under impacts of energetic electrons. By employing the McKinley-Feshbach formalism and accounting for the thermal motion of atoms, we assess the cross section for atom displacement as a function of electron energy. We further investigate the energetics and dynamics of point defects and the stability of ribbons and edges under an electron beam. Finally, we show that P atomic chains should be surprisingly stable, and their atomic structure is not linear giving rise to the absence of a gap in the electronic spectrum. PMID- 27004747 TI - Metabolic flux profiling of MDCK cells during growth and canine adenovirus vector production. AB - Canine adenovirus vector type 2 (CAV2) represents an alternative to human adenovirus vectors for certain gene therapy applications, particularly neurodegenerative diseases. However, more efficient production processes, assisted by a greater understanding of the effect of infection on producer cells, are required. Combining [1,2-(13)C]glucose and [U-(13)C]glutamine, we apply for the first time (13)C-Metabolic flux analysis ((13)C-MFA) to study E1-transformed Madin-Darby Canine Kidney (MDCK) cells metabolism during growth and CAV2 production. MDCK cells displayed a marked glycolytic and ammoniagenic metabolism, and (13)C data revealed a large fraction of glutamine-derived labelling in TCA cycle intermediates, emphasizing the role of glutamine anaplerosis. (13)C-MFA demonstrated the importance of pyruvate cycling in balancing glycolytic and TCA cycle activities, as well as occurrence of reductive alphaketoglutarate (AKG) carboxylation. By turn, CAV2 infection significantly upregulated fluxes through most central metabolism, including glycolysis, pentose-phosphate pathway, glutamine anaplerosis and, more prominently, reductive AKG carboxylation and cytosolic acetyl-coenzyme A formation, suggestive of increased lipogenesis. Based on these results, we suggest culture supplementation strategies to stimulate nucleic acid and lipid biosynthesis for improved canine adenoviral vector production. PMID- 27004748 TI - Thiodigalactoside shows antitumour activity by beta-galactoside-binding protein and regulatory T cells inhibition in oral squamous cell carcinoma. AB - OBJECTIVE: Thiodigalactoside (TDG), a synthetic inhibitor of beta-galactoside binding protein (beta-GBP) suppresses tumour growth by inhibiting multiple cancer enhancing activities of beta-GBP. Hence, we attempted to understand whether disruption of beta-GBP functions and indirect inhibition of Treg cells by TDG affect the growth and establishment of oral cancer cells. METHOD: The growth, morphology, cell cycle regulation, apoptosis induction and angiogenesis of oral cancer cell lines (SCC-4, SCC-9, SCC-25) via MACS-purified Treg cells were performed by MTT, propidium iodide (PI) staining, annexin-V-binding assay and ELISA respectively. RESULTS: Treatment with beta-GBP showed growth-promoting effects on Tregs and oral cancer cells. However, the treatment with its inhibitor TDG resulted in inhibition of Treg subsets and also decreased the frequency of IL10(+) and IL35(+) Tregs indicating its immunomodulatory effects. Additionally, TDG treatment significantly (P < 0.001) inhibited the growth of OSCC cells with a concomitant induction of apoptosis, cell cycle arrest and anti-angiogenesis. CONCLUSION: It appears that TDG concurrently prevents many tumour-promoting effects of beta-GBP in oral cancer cells possibly by Treg inhibition. This offers a preclinical proof of the concept that therapeutic targeting of beta-GBP can overcome Treg -mediated tumour promotion and immunosuppression in oral cancer patients. PMID- 27004749 TI - Unusual case of tacrolimus vascular toxicity after deceased donor renal transplantation. AB - We report a case of tacrolimus vascular toxicity found on a protocol biopsy shortly after a deceased donor renal transplantation. The patient was immunologically high-risk and acute antibody-mediated rejection during post transplant dialysis phase was suspected on the protocol biopsy. Although the patient was stable after treatment of rejection, a further examination showed a very rare but specific side-effect of tacrolimus. It is sometimes difficult to make a differential diagnosis during postoperative dialysis period among AMR, primary non-functioning, drug toxicity, infection or just prolonged recovery from the damage of a long agonal phase on the non-heart beating donor. Although the possibilities of coexistence of rejection or other causes such as infection have not been completely excluded, it is important to be aware of this unusual side effect of tacrolimus. PMID- 27004750 TI - The degree of pi electron delocalization and the formation of 3D-extensible sandwich structures. AB - DFT B3LYP/6-31G(d) calculations were performed to examine the feasibility of graphene-like C42H18 and starbenzene C6(BeH)6 (SBz) polymers as ligands of 3D extensible sandwich compounds (3D-ESCs) with uninterrupted sandwich arrays. The results revealed that sandwich compounds with three or more C42H18 ligands were not feasible. The possible reason may be the localization of pi electrons on certain C6 hexagons due to pi-metal interactions, which makes the whole ligand lose its electronic structure basis (higher degree of pi electron delocalization) to maintain the planar structure. For comparison, with the aid of benzene (Bz) molecules, the SBz polymers can be feasible ligands for designing 3D-ESCs because the C-Be interactions in individual SBz are largely ionic, which will deter the pi electrons on one C6 ring from connecting to those on neighbouring C6 rings. This means that high degree of pi electron delocalization is not necessary for maintaining the planarity of SBz polymers. Such a locally delocalized pi electron structure is desirable for the ligands of 3D-ESCs. Remarkably, the formation of a sandwich compound with SBz is thermodynamically more favourable than that found for bis(Bz)chromium. The assembly of 3D-ESCs is largely exothermic, which will facilitate future experimental synthesis. The different variation trends on the HOMO-LUMO gaps in different directions (relative to the sandwich axes) suggest that they can be developed to form directional conductors or semiconductors, which may be useful in the production of electronic devices. PMID- 27004751 TI - Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer. AB - Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the effect of molecular weight of doped HA on photothermal induction, fluorescence quenching, and drug loading efficiencies. Doxorubicin-loaded HA-doped PPys (DOX@HA-PPys) could be used for imaging and therapy of triple-negative breast cancer (TNBC). Fluorescence turn-on, stimuli-responsive drug release, and photo-induced heating of DOX@HA-PPys enabled not only activatable fluorescence imaging but also subsequent chemo/photothermal dual therapy for TNBC. In particular, we illustrated the potential usefulness of the photothermal effect of the nanoparticles for overcoming chemoresistance in TNBC. PMID- 27004752 TI - Strengthened PAN-based carbon fibers obtained by slow heating rate carbonization. AB - Large efforts have been made over the last 40 years to increase the mechanical strength of polyacrylonitrile (PAN)-based carbon fibers (CFs) using a variety of chemical or physical protocols. In this paper, we report a new method to increase CFs mechanical strength using a slow heating rate during the carbonization process. This new approach increases both the carbon sp(3) bonding and the number of nitrogen atoms with quaternary bonding in the hexagonal carbon network. Theoretical calculations support a crosslinking model promoted by the interstitial carbon atoms located in the graphitic interlayer spaces. The improvement in mechanical performance by a controlled crosslinking between the carbon hexagonal layers of the PAN based CFs is a new concept that can contribute further in the tailoring of CFs performance based on the understanding of their microstructure down to the atomic scale. PMID- 27004754 TI - Separation and identification of phenolic compounds in Bidens pilosa L. by ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. AB - A validated method based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was established to separate and identify phenolic compounds in Bidens pilosa L. Mass spectrometry experiments were performed both in positive and negative ion modes. A total of 35 compounds were detected, and 26 phenolic compounds were unequivocally identified or tentatively assigned based on retention time, maximum UV absorption, molecular formula, and fragments. The ultra high performance liquid chromatography method was validated and showed good linearity (R(2) ? 0.9996) over the test range. The limits of detection and quantification were above 0.072 and 0.162 MUg/mL, respectively. The relative standard deviations of intraday and interday precision were below 0.3 and 1.6%, respectively. PMID- 27004753 TI - CD36 actions in the heart: Lipids, calcium, inflammation, repair and more? AB - CD36 is a multifunctional immuno-metabolic receptor with many ligands. One of its physiological functions in the heart is the high-affinity uptake of long-chain fatty acids (FAs) from albumin and triglyceride rich lipoproteins. CD36 deletion markedly reduces myocardial FA uptake in rodents and humans. The protein is expressed on endothelial cells and cardiomyocytes and at both sites is likely to contribute to FA uptake by the myocardium. CD36 also transduces intracellular signaling events that influence how the FA is utilized and mediate metabolic effects of FA in the heart. CD36 transduced signaling regulates AMPK activation in a way that adjusts oxidation to FA uptake. It also impacts remodeling of myocardial phospholipids and eicosanoid production, effects exerted via influencing intracellular calcium (iCa(2+)) and the activation of phospholipases. Under excessive FA supply CD36 contributes to lipid accumulation, inflammation and dysfunction. However, it is also important for myocardial repair after injury via its contribution to immune cell clearance of apoptotic cells. This review describes recent progress regarding the multiple actions of CD36 in the heart and highlights those areas requiring future investigation. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID- 27004755 TI - Trait- and state-dependent cortical inhibitory deficits in bipolar disorder. AB - OBJECTIVES: Euthymic patients with bipolar disorder (BD) have deficits in cortical inhibition. However, whether cortical inhibitory deficits are trait- or state-dependent impairments is not yet known and their relationship with psychiatric symptoms is not yet understood. In the present study, we examined trait- and state-dependent cortical inhibitory deficits and evaluated the potential clinical significance of these deficits. METHODS: Nineteen patients with bipolar I disorder were evaluated using the paired-pulse transcranial stimulation protocol, which assessed cortical inhibition during an acute manic episode. Cortical inhibition measures were compared with those obtained in 28 demographically matched healthy controls. A follow-up assessment was performed in 15 of these patients three months later, when there was remission from their mood and psychotic symptoms. The association between cortical inhibitory measures and severity of psychiatric symptoms was also studied. RESULTS: During mania, patients showed decreased short-interval intracortical and transcallosal inhibition, as well as a normal cortical silent period and long-interval cortical inhibition. These findings were the same during euthymia. Symptoms associated with motor hyperactivity were correlated negatively with the degree of cortical inhibition. These correlations were not significant when a Bonferroni correction was applied. CONCLUSIONS: The present longitudinal study showed cortical inhibitory deficits in patients with BD, and supports the hypothesis that cortical inhibitory deficits in BD are trait dependent. Further research is necessary to confirm the clinical significance of these deficits. PMID- 27004756 TI - Spontaneous Extradural Hemorrhage in a Patient with Chronic Kidney Disease: A Case Report and Review of Literature. AB - BACKGROUND: Spontaneous extradural hemorrhage is a rare entity. It is usually reported in association with locoregional disease, which is often infective, inflammatory, and hematologic. Chronic kidney disease with hemodialysis is one of the most infrequent causes. The exact association or pathogenesis remains elusive, although possible mechanisms have been suggested. The presentation, associated comorbid conditions, and management vary among the reported cases. CASE DESCRIPTION: A 39-year-old man with hypertension, well controlled with medications, and chronic kidney disease was on maintenance hemodialysis. He later underwent Tenckhoff catheter insertion for peritoneal dialysis; 2 weeks later, when peritoneal dialysis was started, he developed breathlessness. The Tenckhoff catheter was removed. However, the patient developed ascitic leak from the surgical site, which was repaired under general anesthesia. In the immediate postoperative period, he developed sudden, severe headache and was found to have bifrontal extradural hemorrhage. He underwent prompt drainage of the hematoma and was discharged on the fifth postoperative day in stable condition. CONCLUSIONS: We report a rare case of spontaneous bilateral frontal extradural hemorrhage in the immediate postoperative period in a patient on hemodialysis. In addition, we review the existing literature on the topic. PMID- 27004757 TI - Intraventricular Gliosarcomas: Literature Review and a Case Description. AB - OBJECTIVE: Gliosarcomas are rare, extremely high-grade, bimorphous malignant tumors of the central nervous system. Intraventricular location is extremely rare, and only a few case reports exist in the literature. The aim of our study is to review clinical, radiologic, and pathologic features of this unique oncological entity and report this rare case of primary cystic intraventricular gliosarcoma (IVGS) with a mural nodule. METHODS: A 23-year-old man had a 6-month history of headache and a single episode of generalized seizure. Examination revealed grade 1 papilledema. Brain magnetic resonance imaging revealed a cystic lesion with a mural nodule located within the occipital horn of the right lateral ventricle, which exhibited an intense enhancement of the nodule with patchy rim enhancement of the wall on gadolinium administration. The patient underwent right parietal craniotomy and gross total excision of the tumor. RESULTS: Postoperative computed tomography of the brain showed evidence of complete tumor excision. The postoperative course of the patient was uneventful. Histopathologic analysis revealed malignant tumor comprising both glial and mesenchymal components suggestive of gliosarcoma. CONCLUSION: Primary IVGS is an extremely rare malignancy, with only 9 cases reported in the literature, and it should be considered in the differential diagnosis of lateral ventricular tumors. PMID- 27004758 TI - Hypothalamic-Optochiasmatic Pilocytic Astrocytoma Associated with Occipital and Sacral Spinal Cavernomas: A Mere Coincidence or a True Association? AB - BACKGROUND: The co-occurrence of cerebral gliomas and cavernous angiomas is rarely encountered in clinical practice. All reported cases with such association have occurred within the brain with none involving the spinal cord. CASE DESCRIPTION: The authors report the case of a hypothalamic-optochiasmatic pilocytic astrocytoma coexisting with right occipital and sacral spinal cavernomas. This 30-year-old man had an 8-year history of chronic lower back pain. Spinal magnetic resonance imaging (MRI) demonstrated an 8.2-cm expansile multilobulated heterogeneously enhancing intradural mass within the sacral spinal canal, extending into the bilateral S1 and left S2 foramina. Brain MRI depicted a 2.9-cm lobulated heterogeneously enhancing sellar-suprasellar solid and cystic mass expanding the sella and displacing the infundibulum to the right, with a normal-appearing pituitary gland inside the sella, and an extensive supratentorial and infratentorial superficial hemosiderosis. L5-S4 laminectomy and pterional craniotomy were performed for the resection of these lesions. Histopathologic examination revealed a sacral spinal cavernoma and a suprasellar hypothalamic-optochiasmatic pilocytic astrocytoma. CONCLUSION: The coexistence of hypothalamic-optochiasmatic pilocytic astrocytoma and occipital and sacral spinal cavernomas has not been reported previously. Especially for radiologically atypical suprasellar lesions, hypothalamic-optochiasmatic glioma should be included in the differential diagnosis of masses that can expand the sella. Besides previously postulated hypotheses of viral-induced or angiogenic factor induced glial growth, we hypothesize that neoplastic origins of hypothalamic optochiasmatic glioma might be due to the irritative mechanisms resulting from the frequent bleeds occurring from the spinal or cranial cavernoma. PMID- 27004759 TI - Value of Early Postoperative FLAIR Volume Dynamic in Glioma with No or Minimal Enhancement. AB - OBJECTIVE: The evaluation of postoperative magnetic resonance imaging (MRI) in glioma with no or minimal enhancement is controversial because the evaluation of residual tumor volume can be biased. The purpose of this study was to clarify the value of early postoperative and 3-month MRI regarding its validity in predicting recurrent disease. METHODS: For this retrospective, single-center study, overall fluid attenuated inversion recovery (FLAIR) volumes (early postoperative [<48 hours] and 3-month MRI including FLAIR and T1-weighted sequences with and without contrast agent) of 99 patients were assessed using manual segmentation. FLAIR volume dynamic over the first 3 months after surgery and its effect on disease recurrence were evaluated while considering histopathologic features. RESULTS: Overall FLAIR-hyperintense volume significantly decreased between early postoperative and 3-month follow-up MRIs (P < 0.001). Early FLAIR volume increase had a high positive predictive value for overall disease recurrence after resection (85.71% [95%-CI: 62.64-96.24]). Early FLAIR volume dynamic (P < 0.001), isocitrate dehydrogenase 1/2 status (P = 0.002), and preoperative Karnofsky Performance Status (P = 0.012) were observed as independent factors for progression-free survival in multivariate analysis. CONCLUSION: Early postoperative FLAIR volume assessment in gliomas with no or minimal enhancement is susceptible to a systematic overestimation of residual tumors. Nevertheless, early FLAIR volume dynamic is an independent factor for tumor recurrence that should be evaluated in order timely adapt surveillance and therapy regimens accordingly. PMID- 27004760 TI - Enterovirus 71 induces dsRNA/PKR-dependent cytoplasmic redistribution of GRP78/BiP to promote viral replication. AB - GRP78/BiP is an endoplasmic reticulum (ER) chaperone protein with the important function of maintaining ER homeostasis, and the overexpression of GRP78/BiP alleviates ER stress. Our previous studies showed that infection with enterovirus 71 (EV71), a (+)RNA picornavirus, induced GRP78/BiP upregulation; however, ectopic GRP78/BiP overexpression in ER downregulates virus replication and viral particle formation. The fact that a virus infection increases GRP78/BiP expression, which is unfavorable for virus replication, is counterintuitive. In this study, we found that the GRP78/BiP protein level was elevated in the cytoplasm instead of in the ER in EV71-infected cells. Cells transfected with polyinosinic-polycytidylic acid, a synthetic analog of replicative double stranded RNA (dsRNA), but not with viral proteins, also exhibited upregulation and elevation of GRP78/BiP in the cytosol. Our results further demonstrate that EV71 infections induce the dsRNA/protein kinase R-dependent cytosolic accumulation of GRP78/BiP. The overexpression of a GRP78/BiP mutant lacking a KDEL retention signal failed to inhibit both dithiothreitol-induced eIF2alpha phosphorylation and viral replication in the context of viral protein synthesis and viral titers. These data revealed that EV71 infection might cause upregulation and aberrant redistribution of GRP78/BiP to the cytosol, thereby facilitating virus replication. PMID- 27004761 TI - Alum: an old dog with new tricks. AB - Aluminum compounds (alum) are the most widely used adjuvants in veterinary and human vaccines. Alum was initially thought to be a simple depot for antigen retention; however, our understanding of the mechanism by which it works has progressed substantially in recent decades. Nonetheless, consensus regarding its roles in different aspects of immune regulation has not been reached, and it remains a long-standing research subject in the field of vaccinology. This review, in chronological order, discusses the various hypotheses proposed in mostly inadequate attempts to illuminate the mechanism by which alum works, from the depot theory to the involvement of the NLRP3 inflammasome and from cell death associated danger factors to crystalline structure-mediated plasma membrane alteration. In addition, novel findings of unexpected beneficial effects of decreased HBV (Hepatitis B virus) viral load and HBeAg seroconversion in chronically infected patients, as well as significant tumor suppression in experimental mice following multiple alum-only injections are examined, revealing alum's potential clinical applications beyond its use as a simple tool in antigen preparation. With increasing threats of emerging microbes, originating from natural or man-made sources, that pose significant health concerns at the population scale, the potential use of alum as a 'first-aid' vaccine is also discussed. PMID- 27004763 TI - Only a subset of C. canimorsus strains is dangerous for humans. PMID- 27004762 TI - Mortality attributable to carbapenem-resistant Pseudomonas aeruginosa bacteremia: a meta-analysis of cohort studies. AB - Whether carbapenem resistance is associated with mortality in patients with Pseudomonas aeruginosa bacteremia is controversial. To address this issue, we conducted a systematic review and meta-analysis based on cohort studies. We searched PubMed and Embase databases to identify articles (up to April 2015). The DerSimonian and Laird random-effect model was used to generate a summary estimate of effect. Associations were evaluated in subgroups based on different patient characteristics and study quality criteria. Seven studies with a total of 1613 patients were finally included, of which 1 study had a prospective design, and the other 6 were retrospective. Our meta-analysis showed patients with carbapenem resistant P. aeruginosa bacteremia were at a higher risk of death compared with those with carbapenem-susceptible P. aeruginosa bloodstream infections (pooled odds ratio (OR) from three studies reporting adjusted ORs: 3.07, 95% confidence interval (CI), 1.60-5.89; pooled OR from 4 studies only reporting crude ORs: 1.46, 95% CI, 1.10-1.94). The results were robust across a number of stratified analyses and a sensitivity analysis. We also calculated that 8%-18.4% of deaths were attributable to carbapenem resistance in four studies assessing the outcome with 30-day mortality, and these were 3% and 14.6%, respectively, in two studies using 7-day mortality or mortality during bacteremia as an outcome of interest. Carbapenem resistance had a deleterious impact on the mortality of P. aeruginosa bacteremia; however, the results should be interpreted cautiously because only three studies reporting adjusted ORs were included. More large-scale, well designed prospective cohorts, as well as mechanistic studies, are urgently needed in the future. PMID- 27004765 TI - What a downer: The dark side of cannabis. PMID- 27004764 TI - Rotational manipulation of single cells and organisms using acoustic waves. AB - The precise rotational manipulation of single cells or organisms is invaluable to many applications in biology, chemistry, physics and medicine. In this article, we describe an acoustic-based, on-chip manipulation method that can rotate single microparticles, cells and organisms. To achieve this, we trapped microbubbles within predefined sidewall microcavities inside a microchannel. In an acoustic field, trapped microbubbles were driven into oscillatory motion generating steady microvortices which were utilized to precisely rotate colloids, cells and entire organisms (that is, C. elegans). We have tested the capabilities of our method by analysing reproductive system pathologies and nervous system morphology in C. elegans. Using our device, we revealed the underlying abnormal cell fusion causing defective vulval morphology in mutant worms. Our acoustofluidic rotational manipulation (ARM) technique is an easy-to-use, compact, and biocompatible method, permitting rotation regardless of optical, magnetic or electrical properties of the sample under investigation. PMID- 27004767 TI - Neurophysiological investigations for the diagnosis of non-epileptic attack disorder in neuropsychiatry services: from safety standards to improved effectiveness. AB - OBJECTIVE: The discipline of clinical neuropsychiatry currently provides specialised services for a number of conditions that cross the traditional boundaries of neurology and psychiatry, including non-epileptic attack disorder. Neurophysiological investigations have an important role within neuropsychiatry services, with video-electroencephalography (EEG) telemetry being the gold standard investigation for the differential diagnosis between epileptic seizures and non-epileptic attacks. This article reviews existing evidence on best practices for neurophysiology investigations, with focus on safety measures for video-EEG telemetry. METHODS: We conducted a systematic literature review using the PubMed database in order to identify the scientific literature on the best practices when using neurophysiological investigations in patients with suspected epileptic seizures or non-epileptic attacks. RESULTS: Specific measures need to be implemented for video-EEG telemetry to be safely and effectively carried out by neuropsychiatry services. A confirmed diagnosis of non-epileptic attack disorder following video-EEG telemetry carried out within neuropsychiatry units has the inherent advantage of allowing diagnosis communication and implementation of treatment strategies in a timely fashion, potentially improving clinical outcomes and cost-effectiveness significantly. CONCLUSION: The identified recommendations set the stage for the development of standardised guidelines to enable neuropsychiatry services to implement streamlined and evidence-based care pathways. PMID- 27004766 TI - Chronic urticaria and hormones: Is there a link? AB - BACKGROUND: While the role of oestrogens in bradykinin angioedema (AE) has been clearly demonstrated, scarce data are available about the role of sex hormones in chronic urticaria (CU). OBJECTIVES: To gather information from a population of women with various forms of CU [chronic spontaneous urticaria (CSU), including a subtype of isolated histaminic AE and a classic subtype of association of wheals and AE, and exclusive inducible urticaria (IU)] about the impact of sex hormones and reproductive factors on their symptoms. METHODS: This was a cross-sectional study comprising interviews of 200 women consulting for CU at nine centres throughout France between May and July 2013. The dermatologists filled in an online questionnaire on the impact of reproductive factors (puberty, contraception and pregnancy) and hormonal treatments on the course of CU, including CSU and IU, in the presence of the women. RESULTS: Most of the women did not experience CU before puberty and if so, puberty did not influence the course of CU. Only 16 women had experienced a pregnancy during CU which caused a worsening of symptoms in four. Hormonal contraception was associated with aggravation in a minority of women, mostly women with CSU (10%). Women with isolated histaminic AE did not exhibit any female sex hormone dependency. CONCLUSIONS: It would appear that sex hormones act as a trigger in only a small subset of women with CU. Nevertheless, this should be taken into account to improve patient management. PMID- 27004768 TI - An approach to measuring RBC haemolysis and profiling RBC mechanical fragility. AB - Red blood cells (RBC) can be damaged by medical products, from storage or from disease. Haemolysis (cell rupture and haemoglobin release) is often a key indicator, with mechanical fragility (MF) offering the potential to assess sub haemolytic damage as well. This article reports on a unique approach to measuring haemolysis, without the need for centrifugation or other sample separation. It also reports on employing that in measuring blood fragility (susceptibility to haemolysis) under shear stress, utilising an electromagnet to cause a bead to oscillate within a cartridge that contains the sample. Cycling between stressing and optical measurement of induced haemolysis at progressively increasing durations of stress provides a fragility profile. Sub-system-level testing shows high accuracy for the haemolysis measurements and fair consistency for MF profiling. Improving accuracy and precision of profiling is a current focus and a fully integrated and automated version of this system is under development. PMID- 27004770 TI - [Inequality in access to health care services. Policy recommendations aimed at achieving equity]. AB - This article reveals the presence of inequalities in access to health care that may be considered unfair and avoidable. These inequalities are related to coverage of clinical needs, to the financial problems faced by families in completing medical treatments, or to disparities in waiting times and the use of services for equal need. A substantial proportion of inequalities appears to have increased as a result of the measures adopted to face the economic crisis. The recommendations aimed at improving equity affect different pillars of the taxpayer-funded health system, including, among others, the definition of the right to public health care coverage, the formulas of cost-sharing, the distribution of powers between primary and specialty care, the reforms of clinical management, and the production and dissemination of information to facilitate the decision-making processes of health authorities, professionals and citizens. Moreover, it is recommended to focus on particularly vulnerable population groups. PMID- 27004769 TI - Human pentastomiasis in Sub-Saharan Africa. AB - Pentastomiasis is a rare zoonotic infection but it is frequently observed in Africa and Asia. Most human infections are caused by members of the Armillifer armillatus species. They are responsible for visceral pentastomiasis in Western and Central Africa. Humans may be infected by eating infected undercooked snake meat or by direct contact with an infected reptile. An increasing number of infections are being reported in Congo, Nigeria, and Cameroon. Despite an occasionally high number of nymphs observed in human viscera, most infections are asymptomatic and often diagnosed by accident during surgery or autopsy. The clinical presentation of pentastomiasis is quite varied and depends on infected tissues. The liver, lungs, and pleura are most frequently involved. Abdominal emergencies have been reported. Diagnostic delays always occur and diagnosis focuses on the patient's lifestyle and living environment. It is mainly based on the morphological description of the parasite's calcified cuticle, the site of the lesion, and the parasite's region of origin. Most patients do not require any treatment. Personal measures such as avoidance of contact with snake droppings are recommended to prevent transmission. Imported pentastomiasis has been observed in African migrants. PMID- 27004771 TI - CRISPR1 analysis of naturalized surface water and fecal Escherichia coli suggests common origin. AB - Clustered regularly interspaced short palindromic repeats (CRISPRs) are part of an acquired bacterial immune system that functions as a barrier to exogenous genetic elements. Since naturalized Escherichia coli are likely to encounter different genetic elements in aquatic environments compared to enteric strains, we hypothesized that such differences would be reflected within the hypervariable CRISPR alleles of these two populations. Comparison of CRISPR1 alleles from naturalized and fecal phylogroup B1 E. coli strains revealed that the alleles could be categorized into four major distinct groups (designated G6-G9), and all four allele groups were found among naturalized strains and fecal strains. The distribution of CRIPSR G6 and G8 alleles was similar among strains of both ecotypes, while naturalized strains tended to have CRISPR G7 alleles rather than G9 alleles. Since CRISPR G7 alleles were not specific to naturalized strains, they, however, would not be useful as a marker for identifying naturalized strains. Notably, CRISPR alleles from naturalized and fecal strains also had similar spacer repertoires. This indicates a shared history of encounter with mobile genetic elements and suggests that the two populations were derived from common ancestors. PMID- 27004773 TI - Empathy and the clinical teacher. PMID- 27004774 TI - Developing and implementing a patient safety curriculum. PMID- 27004772 TI - Development of Photoactivated Fluorescent N-Hydroxyoxindoles and Their Application for Cell-Selective Imaging. AB - Photoactivatable fluorophores are essential tools for studying the dynamic molecular interactions within important biological systems with high spatiotemporal resolution. However, currently developed photoactivatable fluorophores based on conventional dyes have several limitations including reduced photoactivation efficiency, cytotoxicity, large molecular size, and complicated organic synthesis. To overcome these challenges, we herein report a class of photoactivatable fluorescent N-hydroxyoxindoles formed through the intramolecular photocyclization of substituted o-nitrophenyl ethanol (ONPE). These oxindole fluorophores afford excellent photoactivation efficiency with ultra-high fluorescence enhancement (up to 800-fold) and are small in size. Furthermore, the oxindole derivatives show exceptional biocompatibility by generating water as the only photolytic side product. Moreover, structure activity relationship analysis clearly revealed the strong correlation between the fluorescent properties and the substituent groups, which can serve as a guideline for the further development of ONPE-based fluorescent probes with desired photophysical and biological properties. As a proof-of-concept, we demonstrated the capability of a new substituted ONPE that has an uncaging wavelength of 365-405 nm and an excitation/emission at 515 and 620 nm, for the selective imaging of a cancer cell line (Hela cells) and a human neural stem cell line (hNSCs). PMID- 27004780 TI - Integrating paediatrics into student assistantships. PMID- 27004781 TI - Interprofessional mentorship for final-year medical students. PMID- 27004782 TI - Response to Ten steps to health professional education research. PMID- 27004783 TI - Phacoemulsification in patients unable to lie flat for cataract surgery: Face-to face positioning with surgeon on the contralateral side. PMID- 27004784 TI - Anterior segment optical coherence tomography-guided management of capsular block syndrome following penetrating keratoplasty. PMID- 27004786 TI - The benefits of exploiting rare genetic disorders to better understand human health and disease. PMID- 27004785 TI - Mixing Up the Pieces of the Desferrioxamine B Jigsaw Defines the Biosynthetic Sequence Catalyzed by DesD. AB - Late-stage assembly of the trimeric linear siderophore desferrioxamine B (DFOB) native to Streptomyces pilosus involves two DesD-catalyzed condensation reactions between one N-acetyl-N-hydroxy-1,5-diaminopentane (AHDP) unit and two N-succinyl N-hydroxy-1,5-diaminopentane (SHDP) units. AHDP and SHDP are products of DesBC catalyzed reactions of the native diamine substrate 1,5-diaminopentane (DP). The sequence of DesD-catalyzed DFOB biosynthesis was delineated by analyzing the distribution of DFOB analogues and dimeric precursors assembled by S. pilosus in medium containing 1,4-diamino-2(E)-butene (E-DBE). Seven unsaturated DFOB analogues were produced that were partially resolved by liquid chromatography (LC). Mass spectrometry (MS) measurements reported on the combination of E-DBE- and DP-derived substrates in each trimer (uDFOA1 series, 1:2; uDFOA2 series, 2:1; uDFOA3, 3:0). MS/MS fragmentation patterns reported on the absolute position of the substrate derivative at the N-acetylated terminus, the internal region, or the amine terminus of the trimer. The uDFOA1 and uDFOA2 series each comprised three constitutional isomers (binary notation (DP-derived substrate "0," E-DBE derived substrate "1"); direction, N-acetylated-internal-amine): uDFOA1[001], uDFOA1[010], uDFOA1[100]; and uDFOA2[011], uDFOA2[110], and uDFOA2[101]. E-DBE completely replaced DP in uDFOA3[111]. Relative concentrations of the uDFOA1 series were uDFOA1[001] ? uDFOA1[100] > uDFOA1[010] and of the uDFOA2 series, uDFOA2[101] > uDFOA2[011] ? uDFOA2[110]. Dimeric compounds assembled from one N acetylated and one N-succinylated substrate derivative were detected as trimer precursors: dDFX[00-] ? udDFX[10-] > udDFX[01-] (d = dimer, vacant position "-"). Relative concentrations of all species were consistent with the biosynthetic sequence: (i) SHDP activation, (ii) condensation with AHDP to form AHDP-SHDP, (iii) SHDP activation, and (iv) condensation with AHDP-SHDP to form DFOB. PMID- 27004787 TI - A mitochondrial view of cell fate. PMID- 27004788 TI - Inhibition of phosphorylated Ser473-Akt from translocating into the nucleus contributes to 2-cell arrest and defective zygotic genome activation in mouse preimplantation embryogenesis. AB - Phosphorylated Ser473-Akt (p-Ser473-Akt) is extensively studied as a correlate for the activity of Akt, which plays an important role in mouse oogenesis and preimplantation embryogenesis. However, little progress has been made about its effect on the mouse zygotic genome activation (ZGA) of 2-cell stage in mouse preimplantation embryos. In this study, we confirmed its localization in the pronuclei of 1-cell embryos and found that p-Ser473-Akt acquired prominent nucleus localization in 2-cell embryos physiologically. Akt specific inhibitors API-2 and MK2206 could inhibit the development of mouse preimplantation embryos in vitro, and induce 2-cell arrest at certain concentrations. 2-cell embryos exposed to 2.0 MUmol/L API-2 or 30 MUmol/L MK2206 displayed attenuated immunofluorescence intensity of p-Ser473-Akt in the nucleus. Simultaneously, qRT PCR results revealed that 2.0 MUmol/L API-2 treatment significantly downregulated the mRNA pattern of MuERV-L and eIF-1A, two marker genes of ZGA, suggesting a defect in ZGA compared with that of control group. Collectively, our work demonstrated the nuclear localization of p-Ser473-Akt during major ZGA, and Akt specific inhibitors API-2 and MK2206 which led to 2-cell arrest inhibited p Ser473-Akt from translocating into the nucleus of 2-cell embryos with defective ZGA as well, implying p-Ser473-Akt may be a potential player in the major ZGA of 2-cell mouse embryos. PMID- 27004789 TI - Effects of oxytocin on background anxiety in rats with high or low baseline startle. AB - RATIONALE: Oxytocin has antianxiety properties in humans and rodents. However, the antianxiety effects have been variable. OBJECTIVES: To reduce variability and to strengthen the antianxiety effect of oxytocin in fear-potentiated startle, two experiments were performed. First, different amounts of light-shock pairings were given to determine the optimal levels of cue-specific fear conditioning and non predictable startle (background anxiety). Second, the antianxiety effects of oxytocin were examined in rats with high and low pre-fear conditioning baseline startle to determine if oxytocin differentially affects high and low trait anxiety rats. METHODS: Baseline pre-fear conditioning startle responses were first measured. Rats then received 1, 5, or 10 light-shock pairings. Fear potentiated startle was then tested with two trial types: light-cued startle and non-cued startle trials. In the second experiment, rats fear conditioned with 10 light-shock pairings were administered either saline or oxytocin before a fear potentiated startle test. Rats were categorized as low or high startlers by their pre-fear conditioning startle amplitude. RESULTS: Ten shock pairings produced the largest non-cued startle responses (background anxiety), without increasing cue specific fear-potentiated startle compared to one and five light-shock pairings. Cue-specific fear-potentiated startle was unaffected by oxytocin. Oxytocin reduced background anxiety only in rats with low pre-fear startle responses. CONCLUSIONS: Oxytocin has population selective antianxiety effects on non-cued unpredictable threat, but only in rats with low pre-fear baseline startle responses. The low startle responses are reminiscent of humans with low startle responses and high trait anxiety. PMID- 27004790 TI - Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner. AB - OBJECTIVE: The aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect. METHODS: Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests. Blood samples were collected before and after drug administration for analysis of phosphorylated mTOR level. After behavioral testing, brains were removed for evaluation of brain-derived neurotrophic factor (BDNF) in prefrontal cortex (PFC) and hippocampus. RESULTS: Ketamine normalized hyperactivity of OBX animals in EPM and increased the time spent in open arms. Rapamycin pretreatment resulted in elimination of ketamine effect in EPM test. In CM test, ketamine + rapamycin administration led to cognitive impairment not observed in saline-, ketamine-, or saline + rapamycin-treated OBX rats. Prefrontal BDNF content was significantly decreased, and level of mTOR was significantly elevated in OBX groups. CONCLUSIONS: OBX animals significantly differed from sham controls in most of the tests used. Treatment had more profound effect on OBX phenotype than controls. Pretreatment with rapamycin eliminated the anxiolytic and antidepressant effects of ketamine in task dependent manner. The results indicate that ketamine + rapamycin application resulted in impaired stress responses manifested by cognitive deficits in active place avoidance (CM) test. Intensity of stressor (mild vs. severe) used in the behavioral tests had opposite effect on controls and on OBX animals. PMID- 27004791 TI - EPIG-Seq: extracting patterns and identifying co-expressed genes from RNA-Seq data. AB - BACKGROUND: RNA sequencing (RNA-Seq) measures genome-wide gene expression. RNA Seq data is count-based rendering normal distribution models for analysis inappropriate. Normalization of RNA-Seq data to transform the data has limitations which can adversely impact the analysis. Furthermore, there are a few count-based methods for analysis of RNA-Seq data but they are essentially for pairwise analysis of treatment groups or multiclasses but not pattern-based to identify co-expressed genes. RESULTS: We adapted our extracting patterns and identifying genes methodology for RNA-Seq (EPIG-Seq) count data. The software uses count-based correlation to measure similarity between genes, quasi-Poisson modelling to estimate dispersion in the data and a location parameter to indicate magnitude of differential expression. EPIG-Seq is different than any other software currently available for pattern analysis of RNA-Seq data in that EPIG Seq 1) uses count level data and supports cases of inflated zeros, 2) identifies statistically significant clusters of genes that are co-expressed across experimental conditions, 3) takes into account dispersion in the replicate data and 4) provides reliable results even with small sample sizes. EPIG-Seq operates in two steps: 1) extract the pattern profiles from data as seeds for clustering co-expressed genes and 2) cluster the genes to the pattern seeds and compute statistical significance of the pattern of co-expressed genes. EPIG-Seq provides a table of the genes with bootstrapped p-values and profile plots of the patterns of co-expressed genes. In addition, EPIG-Seq provides a heat map and principal component dimension reduction plot of the clustered genes as visual aids. We demonstrate the utility of EPIG-Seq through the analysis of toxicogenomics and cancer data sets to identify biologically relevant co-expressed genes. EPIG-Seq is available at: sourceforge.net/projects/epig-seq. CONCLUSIONS: EPIG-Seq is unlike any other software currently available for pattern analysis of RNA-Seq count level data across experimental groups. Using the EPIG-Seq software to analyze RNA-Seq count data across biological conditions permits the ability to extract biologically meaningful co-expressed genes associated with coordinated regulation. PMID- 27004792 TI - Ethical analysis in HTA of complex health interventions. AB - BACKGROUND: In the field of health technology assessment (HTA), there are several approaches that can be used for ethical analysis. However, there is a scarcity of literature that critically evaluates and compares the strength and weaknesses of these approaches when they are applied in practice. In this paper, we analyse the applicability of some selected approaches for addressing ethical issues in HTA in the field of complex health interventions. Complex health interventions have been the focus of methodological attention in HTA. However, the potential methodological challenges for ethical analysis are as yet unknown. METHODS: Six of the most frequently described and applied ethical approaches in HTA were critically assessed against a set of five characteristics of complex health interventions: multiple and changing perspectives, indeterminate phenomena, uncertain causality, unpredictable outcomes, and ethical complexity. The assessments are based on literature and the authors' experiences of developing, applying and assessing the approaches. RESULTS: The Interactive, participatory HTA approach is by its nature and flexibility, applicable across most complexity characteristics. Wide Reflective Equilibrium is also flexible and its openness to different perspectives makes it better suited for complex health interventions than more rigid conventional approaches, such as Principlism and Casuistry. Approaches developed for HTA purposes are fairly applicable for complex health interventions, which one could expect because they include various ethical perspectives, such as the HTA Core Model(r) and the Socratic approach. CONCLUSION: This study shows how the applicability for addressing ethical issues in HTA of complex health interventions differs between the selected ethical approaches. Knowledge about these differences may be helpful when choosing and applying an approach for ethical analyses in HTA. We believe that the study contributes to increasing awareness and interest of the ethical aspects of complex health interventions in general. PMID- 27004793 TI - BRCA testing, treatment patterns and survival in platinum-sensitive recurrent ovarian cancer - an observational cohort study. AB - BACKGROUND: Breast cancer associated (BRCA) genes are critical for DNA repair. Mutations in BRCA1 and BRCA2 (BRCAm) result in loss of these repair mechanisms and potential carcinogenesis. Germline BRCAm are common in ovarian carcinomas, particularly in platinum-sensitive disease. The increased prevalence of BRCAm in platinum-sensitive disease is likely due to enhanced responsiveness to platinum chemotherapy from homologous recombination repair deficiency. The purpose of this study was to explore BRCA testing, treatment patterns and survival in platinum sensitive recurrent (PSR) ovarian cancer. METHODS: This was an observational cohort analysis of PSR ovarian cancer treated at the Huntsman Cancer Institute from 1995 to 2012. Germline BRCA status was ascertained through chart review and categorized as BRCAm (BRCA1/2 positive), BRCAwt (BRCA wild type or variant of uncertain significance), and untested. Treatment patterns and survival were assessed from recurrence until death or last follow-up. The Kaplan-Meier method was used to evaluate survival from recurrence by BRCA status. Logistic regression and COX proportional hazard model was used to estimate predictors of BRCA testing and survival, respectively. RESULTS: Of the 168 PSR patients, 15 (9 %) were BRCAm, 25 (15 %) were BRCAwt, and 128 (76 %) were untested. Median age at PSR was 56 years for BRCAm and BRCAwt (p = 0.90) and 63 years for those untested (p = 0.033 vs BRCAm). Overall survival was similar between BRCAm and BRCAwt (median 50.4 vs 67.5 months, p = 0.86) and was 24.9 months in untested patients. Significant predictors for the likelihood of BRCA testing were age (OR = 0.93, 95 % CI 0.89, 0.97, p = 0.002), family history of breast or ovarian cancer (OR = 8.33, 95 % CI: 3.08, 22.59, p < 0.001), and cancer diagnosis year (OR = 10.02, 95 % CI: 3.22, 31.21, p < 0.001). BRCA-tested patients had a lower risk of death versus untested (HR 0.35, 95 % CI 0.17, 0.68, p = 0.001). CONCLUSIONS: BRCAwt patients had similar outcomes to BRCAm patients, potentially owing to similar age at diagnosis, representing a BRCA testing channeling bias. Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested. BRCA tested patients had a lower risk of death. PMID- 27004794 TI - Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury. AB - The purpose of this study was to study whether allergen exposure can induce inflammation and lower the anti-inflammation levels in serum and in adipose tissues, and further develop cardiovascular injury. Our data showed that heart rate was significantly higher in the OVA-challenged mice compared to control mice. Moreover, there were higher expressions of pro-inflammation genes in the OVA-challenged mice in adipose tissues, and the expressions of anti-inflammation genes were lower. The levels of inflammation mediators were associated in serum and adipose tissues. The level of circulatory injury lactate dehydrogenase was significantly associated with the levels of E-selectin, resistin and adiponectin in the serum. The hematoxylin and eosin and immunohistochemistry stains indicated the OVA-challenged mice had higher levels of inflammation. In summary, the current study demonstrated allergen exposure can cause cardiovascular injury, and inflammatory mediators in adipose tissues play an important role in the pathogenesis of cardiovascular injury. PMID- 27004795 TI - Predictors of Poor Pregnancy Outcomes Among Antenatal Care Attendees in Primary Health Care Facilities in Cross River State, Nigeria: A Multilevel Model. AB - Objectives Pregnancy carries a high risk for millions of women and varies by urban-rural location in Nigeria, a country with the second highest maternal deaths in the world. Addressing multilevel predictors of poor pregnancy outcomes among antenatal care (ANC) attendees in primary health care (PHC) facilities could reduce the high maternal mortality rate in Nigeria. This study utilised the "Risk Approach" strategy to (1) compare the risks of poor pregnancy outcomes among ANC attendees by urban-rural location; and (2) determine predictors of poor pregnancy outcomes among ANC attendees in urban-rural PHC facilities in Cross River State, Nigeria. Methods A cross-sectional survey was conducted in 2011 among 400 ANC attendees aged 15-49 years recruited through multistage sampling. Data on risk factors of poor pregnancy outcomes were collected using interviewer administered questionnaires and clinic records. Respondents were categorised into low, medium or high risk of poor pregnancy outcomes, based on their overall risk scores. Predictors of poor pregnancy outcomes were determined by multilevel ordinal logistic regression. Results A greater proportion of the women in the rural areas were below the middle socio-economic quintile (75 vs. 4 %, p < 0.001), had no education (12 vs. 2 %, p < 0.001), and were in the 15-24 age group (58 vs. 35 %, p < 0.001) whereas women in the urban areas were older than 35 years (10 vs. 5 %, p < 0.001). The women attending antenatal care in the urban PHC facilities had a low overall risk of poor pregnancy outcomes than those in the rural facilities (64 vs. 50 %, p = 0.034). Pregnant women in the urban areas had decreased odds of being at high risk of poor pregnancy outcomes versus the combined medium and low risks compared with those in the rural areas (OR 0.55, 95 % CI 0.09-0.65). Conclusions for Practice Pregnant women attending antenatal care in rural PHC facilities are more at risk of poor pregnancy outcomes than those receiving care in the urban facilities. Health programmes that promote safe pregnancy should target pregnant women in rural settings. PMID- 27004796 TI - Host origin and tissue microhabitat shaping the microbiota of the terrestrial isopod Armadillidium vulgare. AB - We present the first in-depth investigation of the host-associated microbiota of the terrestrial isopod crustacean Armadillidium vulgare. This species is an important decomposer of organic matter in terrestrial ecosystems and a major model organism for arthropod-Wolbachia symbioses due to its well-characterized association with feminizing Wolbachia 16S rRNA gene pyrotags were used to characterize its bacterial microbiota at multiple levels: (i) in individuals from laboratory lineages and field populations and (ii) in various host tissues. This integrative approach allowed us to reveal an unexpectedly high bacterial diversity, placing this species in the same league as termites in terms of symbiotic diversity. Interestingly, both animal groups belong to the same ecological guild in terrestrial ecosystems. While Wolbachia represented the predominant taxon in infected individuals, it was not the only major player. Together, the most abundant taxa represented a large scope of symbiotic interactions, including bacterial pathogens, a reproductive parasite (Wolbachia) and potential nutritional symbionts. Furthermore, we demonstrate that individuals from different populations harboured distinct bacterial communities, indicating a strong link between the host-associated microbiota and environmental bacteria, possibly due to terrestrial isopod nutritional ecology. Overall, this work highlights the need for more studies of host-microbiota interactions and bacterial diversity in non-insect arthropods. PMID- 27004797 TI - Jellyfish-associated bacterial communities and bacterioplankton in Indonesian Marine lakes. AB - In the present study, we compared communities of bacteria in two jellyfish species (the 'golden' jellyfish Mastigias cf.papua and the box jellyfish Tripedalia cf.cystophora) and water in three marine lakes located in the Berau region of northeastern Borneo, Indonesia. Jellyfish-associated bacterial communities were compositionally distinct and less diverse than bacterioplankton communities. Alphaproteobacteria, Gammaproteobacteria, Synechococcophycidae and Flavobacteriia were the most abundant classes in water. Jellyfish-associated bacterial communities were dominated by OTUs assigned to the Gammaproteobacteria (family Endozoicimonaceae), Mollicutes, Spirochaetes and Alphaproteobacteria (orders Kiloniellales and Rhodobacterales). Mollicutes were mainly restricted to Mastigias whereas Spirochaetes and the order Kiloniellales were most abundant in Tripedalia hosts. The most abundant OTU overall in jellyfish hosts was assigned to the family Endozoicimonaceae and was highly similar to organisms in Genbank obtained from various hosts including an octocoral, bivalve and fish species. Other abundant OTUs included an OTU assigned to the order Entomoplasmatales and mainly found in Mastigias hosts and OTUs assigned to the Spirochaetes and order Kiloniellales and mainly found in Tripedalia hosts. The low sequence similarity of the Entomoplasmatales OTU to sequences in Genbank suggests that it may be a novel lineage inhabiting Mastigias and possibly restricted to marine lakes. PMID- 27004798 TI - Poorly differentiated clusters (PDC) in colorectal cancer: what is and ought to be known. AB - BACKGROUND: The counting of poorly differentiated clusters of 5 or more cancer cells lacking a gland-like structure in a tumor mass has recently been identified among the histological features predictive of poor prognosis in colorectal cancer. MAIN BODY: Poorly differentiated clusters can easily be recognized in the histological sections of colorectal cancer routinely stained with haematoxylin and eosin. Despite some limitations related to specimen fragmentation, counting can also be assessed in endoscopic biopsies. Based on the number of poorly differentiated clusters that appear under a microscopic field of a *20 objective lens (i.e., a microscopic field with a major axis of 1 mm), colorectal cancer can be graded into malignancies as follows: tumors with <5 clusters as grade 1, tumors with 5 to 9 clusters as grade 2, and tumors with >=10 clusters as grade 3. High poorly differentiated cluster counts are significantly associated with peri neural and lympho-vascular invasion, the presence of nodal metastases or micrometastases, as well as shorter overall and progression free survival to colorectal cancer. CONCLUSION: The morphological aspects and clinical relevance of poorly differentiated clusters counting in colorectal cancer are discussed in this review. PMID- 27004800 TI - The possible mechanisms of subretinal fluid resolution after vitrectomy. PMID- 27004799 TI - Altered striatal intrinsic functional connectivity in pediatric anxiety. AB - Anxiety disorders are among the most common psychiatric disorders of adolescence. Behavioral and task-based imaging studies implicate altered reward system function, including striatal dysfunction, in adolescent anxiety. However, no study has yet examined alterations of the striatal intrinsic functional connectivity in adolescent anxiety disorders. The current study examines striatal intrinsic functional connectivity (iFC), using six bilateral striatal seeds, among 35 adolescents with anxiety disorders and 36 healthy comparisons. Anxiety is associated with abnormally low iFC within the striatum (e.g., between nucleus accumbens and caudate nucleus), and between the striatum and prefrontal regions, including subgenual anterior cingulate cortex, posterior insula and supplementary motor area. The current findings extend prior behavioral and task-based imaging research, and provide novel data implicating decreased striatal iFC in adolescent anxiety. Alterations of striatal neurocircuitry identified in this study may contribute to the perturbations in the processing of motivational, emotional, interoceptive, and motor information seen in pediatric anxiety disorders. This pattern of the striatal iFC perturbations can guide future research on specific mechanisms underlying anxiety. PMID- 27004802 TI - Therapeutic Potential of Human Chorionic Gonadotropin Against Painful Bladder Syndrome/Interstitial Cystitis. AB - Painful bladder syndrome/interstitial cystitis is a debilitating chronic bladder disease that primarily affects women. The disease is due to a damage of urothelial cell lining. As a result, potassium particles and other toxic substances in urine can leak into bladder mucosa, causing the symptoms of lower abdominal/pelvic discomfort, pain, increased urination frequency, urgency, nocturia, and so on, all of which can substantially reduce the quality of daily life. There are multiple symptom reliving therapies. Among them, only pentosan polysulfate sodium, sold under the brand name of Elmiron, has been approved for oral use by US Food and Drug Administration. It provides the relief after several months of use. Based on the scientific leads presented in this article, we propose that human chorionic gonadotropin has a therapeutic potential that is worth investigating for the treatment of this disease. PMID- 27004801 TI - Analysis of Gene Expression in the Endocervical Epithelium of Women With Deep Endometriosis. AB - Endometriosis affects approximately 12% of reproductive-age women and is currently diagnosed using invasive laparoscopic surgery. Differences in gene expression in the eutopic endometrium between women with and without endometriosis have been reported, and determining the reproducibility of these genetic differences in the endocervical epithelium would represent an important step toward developing novel diagnostic strategies. In this study, we analyzed gene expression in the endocervical epithelium in women with and without moderate or severe endometriosis. Using RT2 Profiler PCR Arrays, we analyzed gene expression in endocervical epithelial cells from women with deep endometriosis (n = 4) and healthy women (n =6). Nine genes were identified as being upregulated: 5 cell cycle genes (cyclin B1 [CCNB1], cyclin G1 [CCNG1], cullin 1 [CUL1], general transcription factor IIH, polypeptide 1 [GTF2H1], and proliferating cell nuclear antigen [PCNA]), 3 cytokine genes (C3, chemokine (C-C motif) ligand 21 [CCL21], and chemokine (C-X-C motif) ligand 14 [CXCL14]) and 1 gene related to dendritic cell pathways (ICAM2), showing that differential gene expression is present in the endocervical epithelium of women with deep endometriosis. PMID- 27004803 TI - ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis): A retrospective observational study on biologic drug survival in daily practice. AB - BACKGROUND: Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Previous studies have yielded inconsistent results. OBJECTIVES: We sought to analyze long-term biologic survival and its associated variables in a large, real-life cohort of patients with moderate to severe chronic plaque psoriasis. METHODS: This was an observational retrospective study. Data were extracted from clinical records of 427 patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression. RESULTS: We analyzed 703 treatment courses. Overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months, 95% confidence interval 17.4-28.6) than in patients with body mass index less than 30 (37.3 months, 95% confidence interval 29.4-45.1, P = .001), and it was significantly higher for ustekinumab than for any other biologic agent (log rank test P < .001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment, and PASI75 and PASI90 responses at week 16 prolonged drug survival. LIMITATIONS: Data were collected retrospectively. CONCLUSIONS: These findings can facilitate the daily treatment of psoriatic patients and promote long-term effectiveness of biologic therapies. PMID- 27004804 TI - Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS). AB - BACKGROUND: There is limited information regarding early development of soft tissue and/or bone hypertrophy with facial port-wine stains (PWS). OBJECTIVE: We sought to characterize patients with hypertrophic PWS presenting during childhood. METHODS: Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. RESULTS: A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. LIMITATIONS: As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. CONCLUSION: PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. PMID- 27004805 TI - Release of metal ions from round and rectangular NiTi wires. AB - BACKGROUND: The aim of this study was to evaluate the amount of nickel and titanium ions released from two wires with different shapes and a similar surface area. METHODS: Forty round nickel-titanium (NiTi) arch wires with the diameter of 0.020 in. and 40 rectangular NiTi arch wires with the diameter of 0.016 * 0.016 in. were immersed in artificial saliva during a 21-day period. The surface area of both wires was 0.44 in.(2). Wires were separately dipped into polypropylene tubes containing 50 ml of buffer solution and were incubated and maintained at 37 degrees C. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to measure the amount of ions released after exposure lengths of 1 h, 24 h, 1 week, and 3 weeks. Repeated measures ANOVA and Tukey tests were used to evaluate the data. RESULTS: The results indicated that the amount of nickel and titanium concentrations was significantly higher in the rectangular wire group. The most significant release of all metals was measured after the first hour of immersion. In the rectangular wire group, 243 +/- 4.2 ng/ml of nickel was released after 1 h, while 221.4 +/- 1.7 ng/ml of nickel was released in the round wire group. Similarly, 243.3 +/- 2.8 ng/ml of titanium was released in the rectangular wire group and a significantly lower amount of 211.9 +/- 2.3 ng/ml of titanium was released in the round wire group. CONCLUSIONS: Release of metal ions was influenced by the shape of the wire and increase of time. PMID- 27004806 TI - Impact of nanohydroxyapatite on enamel surface roughness and color change after orthodontic debonding. AB - BACKGROUND: The aim of this prospective in vitro study was to evaluate the effect of nanohydroxyapatite (nanoHAP) serum on the enamel surface roughness and tooth color stability after orthodontic debonding procedure. METHODS: The crowns of 30 premolars were embedded in acrylic blocks with a 4 mm * 5-mm-sized window on the middle third of buccal surfaces. Primary roughness values were evaluated by an atomic force microscope (AFM). After bracket debonding, and polishing procedures, the second roughness parameters were recorded. Specimens were then randomly assigned to two equal groups. NanoHAP serum and HAP toothpaste were applied for 10 days in the first and second groups, respectively. Then, after the third AFM, initial color parameters were measured. Following 1-week immersion in the coffee solution, second color assessment was performed. The fourth AFM was registered after 2 months of aging process. RESULTS: All roughness parameters were elevated following debonding procedure. There was no statistically significant reduction in roughness parameters after 10 days of nanoHAP serum or HAP toothpaste application. Both groups showed significant color change after immersion in the coffee solution. CONCLUSIONS: NanoHAP serum with the protocols used in this study could not restore enamel surfaces to their original condition. PMID- 27004808 TI - Genetic Diversity and Phylogenetic Analysis of South-East Asian Duck Populations Based on the mtDNA D-loop Sequences. AB - The maternally inherited mitochondrial DNA (mtDNA) D-loop region is widely used for exploring genetic relationships and for investigating the origin of various animal species. Currently, domestic ducks play an important role in animal protein supply. In this study, partial mtDNA D-loop sequences were obtained from 145 samples belonging to six South-East Asian duck populations and commercial duck population. All these populations were closely related to the mallard duck (Anas platyrhynchos), as indicated by their mean overall genetic distance. Sixteen nucleotide substitutions were identified in sequence analyses allowing the distinction of 28 haplotypes. Around 42.76% of the duck sequences were classified as Hap_02, which completely matched with Anas platyrhynchos duck species. The neighbor-joining phylogenetic tree also revealed that South-East Asian duck populations were closely related to Anas platyrhynchos. Network profiles were also traced using the 28 haplotypes. Overall, results showed that those duck populations D-loop haplotypes were shared between several duck breeds from Korea and Bangladesh sub continental regions. Therefore, these results confirmed that South-East Asian domestic duck populations have been domesticated from Anas platyrhynchos duck as the maternal origins. PMID- 27004807 TI - ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels and predicts cardiovascular disease risk in Type 2 diabetic Tunisian population. AB - BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is a metabolic factor that increases plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). The objective of this study was to investigate the association of ANGPTL4 variants (E40K and T266M) with triglyceride levels and with cardiovascular risk factors, such as metabolic syndrome (MetS) and obesity in type 2 diabetic Tunisian population. METHODS: We investigated the effect of the tagging single nucleotide polymorphisms (SNPs) rs1044250 (T266M) and rs116843064 (E40K) with triglyceride (TG) levels and CAD risk factors in a cohort of 220 patients undergoing coronary angiography for the evaluation of stable CAD, all of whom had (type 2 diabetes) T2D and were at least overweight. Multivariate logistic regressions were performed on association studies. RESULTS: TT genotype of rs1044250 (T266M variant) showed a protective effect on CVD risk in CAD group patients (OR 1.92, 95% CI 0.601.42, p =0.05) compared with control Group patients (OR 1.17, 95% CI 0.70-1.66, p = 0.72). Likewise, GA genotype of rs116843064 (E40K variant): (OR 0.74, 95% CI 0.54-1.65, p =0.01) for the CAD group compared with control Group patients (OR 1.12, 95% CI 0.68-1.74, p = 0.074). CONCLUSIONS: ANGPTL4 variants are associated with, not only lower fasting triglyceride levels, but also a decreased cardiovascular risk in T2D Tunisian patients. So, T266M and E40K polymorphism predicts cardiovascular disease risk in Type 2 diabetic Tunisian population. PMID- 27004809 TI - Genetic Parameter Estimates of Carcass Traits under National Scale Breeding Scheme for Beef Cattle. AB - Carcass and price traits of 72,969 Hanwoo cows, bulls and steers aged 16 to 80 months at slaughter collected from 2002 to 2013 at 75 beef packing plants in Korea were analyzed to determine heritability, correlation and breeding value using the Multi-Trait restricted maximum likelihood (REML) animal model procedure. The traits included carcass measurements, scores and grades at 24 h postmortem and bid prices at auction. Relatively high heritability was found for maturity (0.41+/-0.031), while moderate heritability estimates were obtained for backfat thickness (0.20+/-0.018), longissimus muscle (LM) area (0.23+/-0.020), carcass weight (0.28+/-0.019), yield index (0.20+/-0.018), yield grade (0.16+/ 0.017), marbling (0.28+/-0.021), texture (0.14+/-0.016), quality grade (0.26+/ 0.016) and price/kg (0.24+/-0.025). Relatively low heritability estimates were observed for meat color (0.06+/-0.013) and fat color (0.06+/-0.012). Heritability estimates for most traits were lower than those in the literature. Genetic correlations of carcass measurements with characteristic scores or quality grade of carcass ranged from -0.27 to +0.21. Genetic correlations of yield grade with backfat thickness, LM area and carcass weight were 0.91, -0.43, and -0.09, respectively. Genetic correlations of quality grade with scores of marbling, meat color, fat color and texture were -0.99, 0.48, 0.47, and 0.98, respectively. Genetic correlations of price/kg with LM area, carcass weight, marbling, meat color, texture and maturity were 0.57, 0.64, 0.76, -0.41, -0.79, and -0.42, respectively. Genetic correlations of carcass price with LM area, carcass weight, marbling and texture were 0.61, 0.57, 0.64, and -0.73, respectively, with standard errors ranging from +/-0.047 to +/-0.058. The mean carcass weight breeding values increased by more than 8 kg, whereas the mean marbling scores decreased by approximately 0.2 from 2000 through 2009. Overall, the results suggest that genetic improvement of productivity and carcass quality could be obtained under the national scale breeding scheme of Korea for Hanwoo and that continuous efforts to improve the breeding scheme should be made to increase genetic progress. PMID- 27004810 TI - Effects of Medicinal Herb Extracts on In vitro Ruminal Methanogenesis, Microbe Diversity and Fermentation System. AB - This study was aimed to evaluate the in vitro effects of medicinal herb extracts (MHEs) on ruminal fermentation characteristics and the inhibition of protozoa to reduce methane production in the rumen. A fistulated Hanwoo was used as a donor of rumen fluid. The MHEs (T1, Veratrum patulum; T2, Iris ensata var. spontanea; T3, Arisaema ringens; T4, Carduus crispus; T5, Pueraria thunbergiana) were added to the in vitro fermentation bottles containing the rumen fluid and medium. Total volatile fatty acid (tVFA), total gas production, gas profiles, and the ruminal microbe communities were measured. The tVFA concentration was increased or decreased as compared to the control, and there was a significant (p<0.05) difference after 24 h incubation. pH and ruminal disappearance of dry matter did not show significant difference. As the in vitro ruminal fermentation progressed, total gas production in added MHEs was increased, while the methane production was decreased compared to the control. In particular, Arisaema ringens extract led to decrease methane production by more than 43%. In addition, the result of real-time polymerase chain reaction indicted that the protozoa population in all added MHEs decreased more than that of the control. In conclusion, the results of this study indicated that MHEs could have properties that decrease ruminal methanogenesis by inhibiting protozoa species and might be promising feed additives for ruminants. PMID- 27004811 TI - Effects of Coated Compound Proteases on Apparent Total Tract Digestibility of Nutrients and Apparent Ileal Digestibility of Amino Acids for Pigs. AB - Two experiments were conducted to evaluate effects of coated compound proteases (CC protease) on apparent total tract digestibility (ATTD) of nitrogen (N) and energy, and apparent ileal digestibility (AID) of amino acids (AA) and nutrients in diets for pigs. In Exp. 1, 12 crossbred barrows (initial body weight: 20.14+/ 1.71 kg) were housed in individual metabolism crates and allotted into 2 treatments with 6 piglets per treatment according to weight in a randomized complete block design. The 2 diets were corn-soybean meal basal diets with (0.2 g/kg) or without CC protease supplementation. The CC protease supplementation increased (p<0.05) the digestible and metabolizable N and energy values and the digestibility and retention rate of N in the diet. The ATTD of energy and nutrients had been improved (p<0.05) in the diet supplemented with CC protease. In Exp. 2, 12 crossbred barrows (initial body weight: 20.79+/-1.94 kg), fitted with T-cannulas at the distal ileum, were blocked by body weight into 2 groups with 6 pigs each. The diets were the same as those in Exp. 1. The CC protease increased (p<0.05) the AID of crude protein and some essential AA including arginine, isoleucine and leucine. The AID and ATTD of energy and nutrients had been improved (p<0.05) by supplemental CC protease, but the hindgut digestibility of nutrients was unaffected. Overall, the CC protease improved the ATTD of N and energy and AID of some indispensible AA and nutrients in the corn-soybean meal diet for pigs. Therefore, the CC protease supplement could improve the utilization of protein in the corn-soybean meal diet and thus contribute to lower N excretion to the environment. PMID- 27004812 TI - Cloning and Expression of Yak Active Chymosin in Pichia pastoris. AB - Rennet, a complex of enzymes found in the stomachs of ruminants, is an important component for cheese production. In our study, we described that yak chymosin gene recombinant Pichia pastoris strain could serve as a novel source for rennet production. Yaks total RNA was extracted from the abomasum of an unweaned yak. The yak preprochymosin, prochymosin, and chymosin genes from total RNA were isolated using gene specific primers based on cattle chymosin gene sequence respectively and analyzed their expression pattern byreal time-polymerase chain reaction. The result showed that the chymosin gene expression level of the sucking yaks was 11.45 times higher than one of adult yaks and yak chymosin belongs to Bovidae family in phylogenetic analysis. To express each, the preprochymosin, prochymosin, and chymosin genes were ligated into the expression vector pPICZalphaA, respectively, and were expressed in Pichia pastoris X33. The results showed that all the recombinant clones of P. pastoris containing the preprochymosin, prochymosin or chymosin genes could produce the active form of recombinant chymosin into the culture supernatant. Heterologous expressed prochymosin (14.55 Soxhlet unit/mL) had the highest enzyme activity of the three expressed chymosin enzymes. Therefore, we suggest that the yak chymosin gene recombinant Pichia pastoris strain could provide an alternative source of rennet production. PMID- 27004813 TI - Effects of Supplements with Different Protein Contents on Nutritional Performance of Grazing Cattle During the Rainy Season. AB - The objective of this study was to evaluate the effects of supplements with different crude protein (CP) contents on grazing cattle intake, digestibility, ruminal fermentation pattern, and nitrogen (N) metabolism characteristics during the rainy season. Five ruminal and abomasal cannulated Holstein*Zebu steers (296 kg body weight, BW) were used in a 5*5 Latin square design. The animals grazed five signal grass paddocks (0.34 ha). The five treatments evaluated were: Control (no supplement) and 1.0 g of supplement/kg BW with 0, 330, 660, and 1,000 g of CP/kg as-fed. The supplement was composed of starch, soybean meal, urea, and ammonium sulphate. There was a positive linear effect (p<=0.033) of the CP content in the supplements on the organic matter (OM), CP, and digested OM intakes. The provision of supplements did not increase (p>=0.158), on average, total and ruminal digestibilities of OM and CP. However, the increase in CP content in the supplements caused a positive linear effect (p<=0.018) on ruminal digestibilities of OM and CP. Additionally, a quadratic effect of the CP contents of the supplements were observed (p = 0.041) for the ruminal digestibility of neutral detergent fiber corrected for ash and protein, with the highest estimate obtained with the CP content of 670 g/kg. The supply of supplements increased (p<0.001) the ruminal ammonia N concentration, which also changed linearly and positively (p<0.001) according to increase in CP content in the supplements. The apparent N balance and relative N balance (g/g N intake) were not, on average, changed (p>=0.164) by the supplements supply. However, both showed a tendency of a linear increase (p<=0.099) with increasing supplement CP content. The supplements increased (p = 0.007) microbial N production in the rumen, which also changed linearly and positively (p = 0.016) with increasing supplement CP content. In conclusion, protein supplementation in grazing cattle during the rainy season, while stimulating voluntary forage intake, results in higher efficiency of N utilization when compared to energy supplementation. This is a possible response to increased microbial protein synthesis in the rumen and improved N status in the animal body. PMID- 27004814 TI - Conservation of indigenous cattle genetic resources in Southern Africa's smallholder areas: turning threats into opportunities - A review. AB - The current review focuses on characterization and conservation efforts vital for the development of breeding programmes for indigenous beef cattle genetic resources in Southern Africa. Indigenous African cattle breeds were identified and characterized using information from refereed journals, conference papers and research reports. Results of this current review reviewed that smallholder beef cattle production in Southern Africa is extensive and dominated by indigenous beef cattle strains adaptable to the local environment. The breeds include Nguni, Mashona, Tuli, Malawi Zebu, Bovino de Tete, Angoni, Landim, Barotse, Twsana and Ankole. These breeds have important functions ranging from provision of food and income to socio-economic, cultural and ecological roles. They also have adaptive traits ranging from drought tolerant, resistance to ticks and tick borne diseases, heat tolerance and resistance to trypanosomosis. Stakeholders in the conservation of beef cattle were also identified and they included farmers, national government, research institutes and universities as well as breeding companies and societies in Southern Africa. Research efforts made to evaluate threats and opportunities of indigenous beef cattle production systems, assess the contribution of indigenous cattle to household food security and income, genetically and phenotypically characterize and conserve indigenous breeds, and develop breeding programs for smallholder beef production are highlighted. Although smallholder beef cattle production in the smallholder farming systems contributes substantially to household food security and income, their productivity is hindered by several constraints that include high prevalence of diseases and parasites, limited feed availability and poor marketing. The majority of the African cattle populations remain largely uncharacterized although most of the indigenous cattle breeds have been identified. PMID- 27004815 TI - The Nutritive Values in Different Varieties of Corn Planted in One Location Fed to Growing Pigs over Three Consecutive Years. AB - This experiment was conducted to determine the effect of variety and planting year on the nutritive values of corn fed to growing pigs. Four corn varieties examined in this experiment were planted in the same village located in Longhua County, Heibei Province, China, in 2012, 2013, and 2014, respectively. During each year, corn was hand-harvested in early October and sun dried to about 14% moisture content. Three batches of twenty-four barrows (33.27+/-4.30, 31.88+/ 2.93, 34.21+/-3.81 kg body wight [BW] in 2012, 2013, and 2014, respectively) were used and allotted to a complete block design with 4 diets and 6 replicate pigs per diet. Pigs were individually placed in metabolic crates. The four experimental diets were formulated by mixing each variety of corn and vitamins and minerals, respectively. A five-day collection period followed a seven-day diet acclimation period. The results indicated that variety of corn significantly influenced the available energy content (digestible energy [DE] on dry matter basis, p<0.05; metabolizable energy (ME) on dry matter basis, p<0.05, respectively), and the apparent total tract digestibility (ATTD) of organic matter (p<0.01), dry matter (p<0.05), gross energy (p<0.05), neutral detergent fiber (p<0.01), acid detergent fiber and ether extract (p<0.05). The planting year also significantly influenced the available energy contents (DE on dry matter basis, p<0.05; ME on dry matter basis, p<0.01, respectively) and the ATTD of neutral detergent fiber (p<0.01), acid detergent fiber (p<0.01), crude protein (p<0.01), and ether extract (p<0.01). No interaction was observed between the variety and planting year in DE and ME contents in corn. In conclusion, the variety and planting year significantly influenced the available energy and nutrient digestibility of corn fed to growing pigs. PMID- 27004816 TI - Performance Responses, Nutrient Digestibility, Blood Characteristics, and Measures of Gastrointestinal Health in Weanling Pigs Fed Protease Enzyme. AB - Although exogenous protease enzymes have been used in poultry diets quite extensively, this has not been the case for pig diets. In general, due to their better gut fermentative capacity and longer transit time, pigs have greater capacity to digest dietary proteins than poultry. However, in early-weaned piglets, the stress brought about by weaning adversely affects the digestion of dietary proteins. Therefore, a study was conducted to determine the effects of a commercial protease enzyme in weanling pigs. Indices of growth, nutrient digestibility, blood profiles, fecal microflora, fecal gas emission and fecal scores were measured during the study. A total of 50 weanling pigs (6.42+/-0.12 kg) at 28 d of age were randomly assigned to receive 1 of 2 dietary treatments: i) control diet (corn-soy based) with no supplemental protease (CON), and ii) control diet+200 g/ton protease (PROT) for 42 d. A completely randomized design consisting of 2 treatments, 5 replicates, and 5 pigs in each replicate was used. Growth performance in terms of body weight (27.04+/-0.38 kg vs 25.75+/-0.39 kg; p<0.05) and average daily gain (491+/-7.40 g vs 460+/-7.46 g; p<0.05) in PROT fed pigs were increased significantly, but gain per feed (0.700+/-0.01 vs 0.678+/ 0.01; p>0.05) was similar between treatments at d 42. Relative to CON pigs, PROT fed pigs had increased (p<0.05) apparent total tract digestibility (84.66%+/ 0.65% vs 81.21%+/-1.13% dry matter and 84.02%+/-0.52% vs 80.47%+/-1.22% nitrogen) and decreased (p<0.05) NH3 emission (2.0+/-0.16 ppm vs 1.2+/-0.12 ppm) in the feces at d 42. Except for a decreased (p<0.05) in blood creatinine level, no differences were observed in red blood cell, white blood cell, lymphocyte, urea nitrogen, and IgG concentrations between treatments. Fecal score and fecal microflora (Lactobacillus and E. coli) were also similar between CON and PROT groups. Overall, the supplementation of protease enzyme in weanling pigs resulted in improved growth rate and nutrient digestibility. Exogenous protease enzyme reduced fecal NH3 emission, thus, potentially serving as a tool in lowering noxious gas contribution of livestock production in the environment. PMID- 27004817 TI - Dietary Niacin Supplementation Suppressed Hepatic Lipid Accumulation in Rabbits. AB - An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32) were allocated to two equal treatment groups: Fed basal diet (control) or fed basal diet with additional 200 mg/kg niacin supplementation (niacin). The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p<0.05), but significantly decreased the hepatic fatty acid synthase activity and adiponectin receptor 2, insulin receptor and acetyl-CoA carboxylase mRNA levels (p<0.05). Plasma insulin had a decreasing tendency in the niacin treatment group compared with control (p = 0.067). Plasma very low density lipoproteins, leptin levels and the hepatic adiponectin receptor 1 and carnitine palmitoyl transferase 1 genes expression were not significantly altered with niacin addition to the diet (p>0.05). However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (p<0.05). In conclusion, niacin treatment can decrease hepatic fatty acids synthesis, but does not alter fatty acids oxidation and triacylglycerol export. And this whole process attenuates lipid accumulation in liver. Besides, the hormones of insulin, leptin and adiponectin are associated with the regulation of niacin in hepatic lipid metabolism in rabbits. PMID- 27004818 TI - Molecular Cloning, mRNA Expression, and Localization of the G-protein Subunit Galphaq in Sheep Testis and Epididymis. AB - The reproductive function of G-protein subunit Galphaq (GNAQ), a member of the G protein alpha subunit family, has been extensively studied in humans and rats. However, no data is available on its status in ruminants. The objectives of this study were to evaluate the expression pattern of the GNAQ in the testis and epididymis of sheep by polymerase chain reaction (PCR). The mRNA expression levels were detected by real-time fluorescent quantitative PCR, and cellular localization of GNAQ in the testis and epididymis was examined by immunohistochemistry. Additionally, GNAQ protein was qualitatively evaluated via western blot, with the results indicating that similarities between GNAQ mRNA levels from sheep was highly conserved with those observed in Bos taurus and Sus scrofa. Our results also indicated that GNAQ exists in the caput and cauda epididymis of sheep, while GNAQ in the testis and epididymis was localized to Leydig cells, spermatogonial stem cells, spermatocytes, Sertoli cells, spermatid, principal cells, and epididymis interstitial cells. The concentrations of GNAQ mRNA and protein in the caput and cauda epididymis were significantly greater than those observed in the corpus epididymis (p<0.01) and testis (p<0.05). Our results indicated that GNAQ exists at high concentrations in the caput and cauda epididymis of sheep, suggesting that GNAQ may play an important role in gonad development and sperm maturation. PMID- 27004819 TI - Influence of Horse and Rider on Stress during Horse-riding Lesson Program. AB - The present study aims to confirm the influence of a horse-riding lesson program (HRLP) on the stress level of horses and riders by respectively analyzing their salivary cortisol concentration. Twenty-four healthy horses and 23 riders participated in this study. The horses were randomly classified into two groups for the horse riding lesson program: Class 1 (for the beginner lesson) and Class 2 (for the intermediate lesson). The Class 1 group consisted of 12 horses and 12 riders, while the Class 2 group consisted of 12 horses and 11 riders. Salivettes cotton wool swabs were used for saliva collection and the saliva analyses were conducted using a two-way analysis of variance for repeated measures with SAS version 8. As for the results, the average salivary cortisol concentration of all horses before HRLP significantly increased compared to the baseline (p<0.001) while it decreased after the HRLP. The results of the salivary cortisol concentration of the riders were similar to the horses' results. However, there was no difference during the HRLP between Class 1 and Class 2 in the horse or rider groups. The results suggest that the HRLP did not influence the stress level of the horses or riders. Thus, this study provides the necessary information and guidelines for future studies on stress in horses during riding and gives insight into better horse welfare and management options. PMID- 27004821 TI - Ileal Amino Acid Digestibility of Broken Rice Fed to Postweaned Piglets with or without Multicarbohydrase and Phytase Supplementation. AB - Most of amino acid (AA) digestibility values for feed ingredients are obtained using pigs cannulated in the distal ileum. The ileal-cannulated pig model uses pigs older than six weeks due to difficulties related to implanting the T-cannula in distal ileum of younger pigs and complications during the post-surgical recovery. However, to properly formulate the diet of weaned pigs, the nutritive value of feed ingredients should be determined with younger pigs. Thus, 25 weaned pigs were used to determine the apparent total tract digestibility (ATTD) of nutrients, energy, and apparent ileal digestibility (AID) and standardized ileal digestibility (SID) ileal AA digestibility of broken rice (BR), with or without multicarbohydrase (MC) and phytase (Phy) supplementation. Piglets were weaned at 23 d of age and individually housed in digestibility cages until 45 d of age. The trial consisted of 7 d of adaptation to the experimental diets and 3 d of excreta (feces and urine) collection. Ileal digesta was collected at slaughter (about 6 weeks of age). A completely randomized experimental design was used to determine the effects of MC and Phy. Reference diets (RD, 5% casein) was replaced by 30% of BR with or without MC, Phy, or MC+Phy. The RD was used to quantify endogenous AA losses. BR with Phy supplied had increased the ATTD of dry matter (p<0.05) and SID of histidine (p = 0.05), arginine, leucine, lysine, valine, alanine, and proline (p<0.05). BR with MC had been increased digestible energy and protein and SID for histidine (p<0.05). There was no interaction between Phy and MC on the BR nutrient digestibilities. Standardized amino acid digestibilities of BR, without enzymes, were lower than those values reported in the literature. The MC and Phy improved the digestibility of some nutrients and energy of BR in post-weaned piglet diets. PMID- 27004820 TI - Effects of exogenous phytase and xylanase, individually or in combination, and pelleting on nutrient digestibility, available energy content of wheat and performance of growing pigs fed wheat-based diets. AB - OBJECTIVE: Two experiments were conducted to determine the effects of adding exogenous phytase and xylanase, individually or in combination, as well as pelleting on nutrient digestibility, available energy content of wheat and the performance of growing pigs fed wheat-based diets. METHODS: In Experiment 1, forty-eight barrows with an initial body weight of 35.9+/-0.6 kg were randomly assigned to a 2*4 factorial experiment with the main effects being feed form (pellet vs meal) and enzyme supplementation (none, 10,000 U/kg phytase, 4,000 U/kg xylanase or 10,000 U/kg phytase plus 4,000 U/kg xylanase). The basal diet contained 97.8% wheat. Pigs were placed in metabolic cages for a 7-d adaptation period followed by a 5-d total collection of feces and urine. Nutrient digestibility and available energy content were determined. Experiment 2 was conducted to evaluate the effects of pelleting and enzymes on performance of wheat for growing pigs. In this experiment, 180 growing pigs (35.2+/-9.0 kg BW) were allocated to 1 of 6 treatments according to a 2*3 factorial treatment arrangement with the main effects being feed form (meal vs pellet) and enzyme supplementation (0, 2,500 or 5,000 U/kg xylanase). RESULTS: In Experiment 1, there were no interactions between feed form and enzyme supplementation. Pelleting reduced the digestibility of acid detergent fiber (ADF) by 6.4 percentage units (p<0.01), increased the digestibility of energy by 0.6 percentage units (p<0.05), and tended to improve the digestibility of crude protein by 0.5 percentage units (p = 0.07) compared with diets in mash form. The addition of phytase improved the digestibility of phosphorus (p<0.01) and calcium (p<0.01) by 6.9 and 7.6 percentage units respectively compared with control group. Adding xylanase tended to increase the digestibility of crude protein by 1.0 percentage units (p = 0.09) and increased the digestibility of neutral detergent fiber (NDF) (p<0.01) compared with control group. Supplementation of the xylanase-phytase combination improved the digestibility of phosphorus (p<0.01) but impaired NDF digestibility (p<0.05) compared with adding xylanase alone. In Experiment 2, adding xylanase increased average daily gain (p<0.01) and linearly improved the feed:gain ratio (p<0.01) compared with control group. CONCLUSION: Pelleting improved energy digestibility but decreased ADF digestibility. Adding xylanase increased crude protein digestibility and pig performance. Phytase increased the apparent total tract digestibility of phosphorus and calcium. The combination of phytase-xylanase supplementation impaired the effects of xylanase on NDF digestibility. PMID- 27004822 TI - Effects of Replacing Pork Back Fat with Canola and Flaxseed Oils on Physicochemical Properties of Emulsion Sausages from Spent Layer Meat. AB - The objective of this study was to investigate the effects of canola and flaxseed oils on the physicochemical properties and sensory quality of emulsion-type sausage made from spent layer meat. Three types of sausage were manufactured with different fat sources: 20% pork back fat (CON), 20% canola oil (CA) and 20% flaxseed oil (FL). The pH value of the CA was significantly higher than the others (p<0.05). The highest water holding capacity was also presented for CA; in other words, CA demonstrated a significantly lower water loss value among the treatments (p<0.05). CA had the highest lightness value (p<0.05). However, FL showed the highest yellowness value (p<0.05) because of its own high-density yellow color. The texture profile of the treatments manufactured with vegetable oils showed higher values than for the CON (p<0.05); furthermore, CA had the highest texture profile values (p<0.05) among the treatments. The replacement of pork back fat with canola and flaxseed oils in sausages significantly increased the omega-3 fatty acid content (p<0.05) over 15 to 86 times, respectively. All emulsion sausages containing vegetable oil exhibited significantly lower values for saturated fatty acid content and the omega-6 to omega-3 ratios compared to CON (p<0.05). The results show that using canola or flaxseed oils as a pork fat replacer has a high potential to produce healthier products, and notably, the use of canola oil produced characteristics of great emulsion stability and sensory quality. PMID- 27004824 TI - The role of micro health insurance in providing financial risk protection in developing countries--a systematic review. AB - BACKGROUND: Out of pocket payments are the predominant method of financing healthcare in many developing countries, which can result in impoverishment and financial catastrophe for those affected. In 2010, WHO estimated that approximately 100 million people are pushed below the poverty line each year by payments for healthcare. Micro health insurance (MHI) has been used in some countries as means of risk pooling and reducing out of pocket health expenditure. A systematic review was conducted to assess the extent to which MHI has contributed to providing financial risk protection to low-income households in developing countries, and suggest how the findings can be applied in the Pakistani setting. METHODS: We conducted a systematic search for published literature using the search terms "Community based health insurance AND developing countries", "Micro health insurance AND developing countries", "Mutual health insurance AND developing countries", "mutual OR micro OR community based health insurance" "Health insurance AND impact AND poor" "Health insurance AND financial protection" and "mutual health organizations" on three databases, Pubmed, Google Scholar and Science Direct (Elsevier). Only those records that were published in the last ten years, in English language with their full texts available free of cost, were considered for inclusion in this review. Hand searching was carried out on the reference lists of the retrieved articles and webpages of international organizations like World Bank, World Health Organization and International Labour Organization. RESULTS: Twenty-three articles were eligible for inclusion in this systematic review (14 from Asia and 9 from Africa). Our analysis shows that MHI, in the majority of cases, has been found to contribute to the financial protection of its beneficiaries, by reducing out of pocket health expenditure, catastrophic health expenditure, total health expenditure, household borrowings and poverty. MHI also had a positive safeguarding effect on household savings, assets and consumption patterns. CONCLUSION: Our review suggests that MHI, targeted at the low-income households and tailored to suit the cultural and geographical structures in the various areas of Pakistan, may contribute towards providing protection to the households from catastrophe and impoverishment resulting from health expenditures. This paper emphasizes the need for further research to fill the knowledge gap that exists about the impact of MHI, using robust study designs and impact indicators. PMID- 27004826 TI - Microbial Endurance: In It for the Long Haul. PMID- 27004827 TI - Studying Bacterial Multispecies Biofilms: Where to Start? AB - The high prevalence and significance of multispecies biofilms have now been demonstrated in various bacterial habitats with medical, industrial, and ecological relevance. It is highly evident that several species of bacteria coexist and interact in biofilms, which highlights the need for evaluating the approaches used to study these complex communities. This review focuses on the establishment of multispecies biofilms in vitro, interspecies interactions in microhabitats, and how to select communities for evaluation. Studies have used different experimental approaches; here we evaluate the benefits and drawbacks of varying the degree of complexity. This review aims to facilitate multispecies biofilm research in order to expand the current limited knowledge on interspecies interactions. PMID- 27004828 TI - Adverse Cardiac Events and the Impaired Relaxation Left Ventricular Filling Pattern. AB - BACKGROUND: Increasing diastolic dysfunction (DD) grade is associated with increased heart failure (HF). Patients with preserved ejection fractions and grade 1 DD may have left atrial dilatation, e' < 8 cm/sec, increased left ventricular (LV) mass, or variable E/e' ratios. The aim of this study was to test the hypothesis that LV hypertrophy or E/e' ratio > 8 may be associated with a greater incidence of HF. METHODS: Two hundred twelve patients with grade 1 DD and ejection fractions > 50% were retrospectively studied. Group 1 comprised 108 patients with E/A ratios < 0.8, without LV hypertrophy, e' < 8 cm/sec, and E/e' ratios < 8. Group 2 comprised 104 patients with LV hypertrophy or E/e' ratios > 8. Patients with incident HF and valvular or coronary disease were excluded. Using two-dimensional Doppler echocardiography, LV and left atrial volumes and transmitral spectral and tissue Doppler were analyzed. Medical records were examined for laboratory data, HF admissions, and all-cause mortality from 2004 to 2012. RESULTS: Despite similar ejection fractions, patients in group 2 had greater LV and left atrial volumes, LV mass index values, and E/e' ratios (P < .01 for all). HF incidence was greater in group 2 (30 vs 4, P < .001). Combined HF or all-cause mortality was greater in group 2 (46 vs 14, P < .001). Multivariate analysis revealed that HF was associated with E/e' ratio (P < .0001), systolic blood pressure (P = .0123), and LV mass index (P = .042). Combined HF or all-cause mortality was associated with E/e' ratio (P < .0001), LV mass index (P = .009), and lower calcium channel blocker use (P = .0011). CONCLUSIONS: HF alone or HF and all-cause mortality were increased in patients with grade 1 DD in the presence of LV hypertrophy or elevated LV filling pressures. PMID- 27004829 TI - Explaining Differentials in Subsidy Levels Among Hospital Ownership Types in Germany. AB - German hospitals receive subsidies for investment costs by federal states. Theoretically, these subsidies have to cover the whole investment volume, but in fact, only 50-60% are covered. Balance sheet data show that public hospitals exhibit higher levels of subsidies compared with for-profit hospitals. In this study, I examine the sources of this disparity by decomposing the differential in a so-called facilitation ratio, that is, the ratio of subsidies to tangible fixed assets, revealing to which extent assets are funded by subsidies. The question of interest is whether the differential can be attributed to observable hospital specific and federal state-specific characteristics or to unobservable factors. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27004825 TI - Stress as a Normal Cue in the Symbiotic Environment. AB - All multicellular hosts form associations with groups of microorganisms. These microbial communities can be taxonomically diverse and dynamic, and their persistence is due to robust, and sometimes coevolved, host-microbe and microbe microbe interactions. Chemical and physical sources of stress are prominently situated in this molecular exchange, as cues for cellular responses in symbiotic microbes. Stress in the symbiotic environment may arise from three sources: host tissues, microbe-induced immune responses, or other microbes in the host environment. The responses of microbes to these stresses can be general or highly specialized, and collectively may contribute to the stability of the symbiotic system. In this review, we highlight recent work that emphasizes the role of stress as a cue in the symbiotic environment of plants and animals. PMID- 27004830 TI - The application of information theory for the research of aging and aging-related diseases. AB - This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease. PMID- 27004831 TI - Severe tooth loss after root damage caused by predrilled intermaxillary fixation screw: a case report. AB - Intermaxillary fixation (IMF) with screws is routinely used as a conservative therapy or to obtain normal occlusion during the surgical procedure of open reduction and internal fixation for treating mandibular fractures. The risk of iatrogenic dental damage caused by interdental drilling is widely known. Several side effects are described, including loss of response to pulp sensibility testing, root fracture, and, loss of the tooth. This is a case report about a young man who had undergone temporary IMF treatment with a single proven root damage. The patient did not appear for follow-up but he presented 5 years afterward with local purulent osteomyelitis concerning the affected and the adjacent teeth. Osteotomy and extraction of two premolars and one molar were necessary for rehabilitation. This case report illustrates the importance of careful use of predrilled IMF screws and the necessity of frequent follow-ups in cases of proven tooth root damage due to IMF treatment. PMID- 27004832 TI - Human, Pig, and Mouse Interferon-Induced Transmembrane Proteins Partially Restrict Pseudotyped Lentiviral Vectors. AB - Lentiviral vectors are increasingly used in clinical trials to treat genetic diseases. Our research has focused on strategies to improve lentiviral gene transfer efficiency in the airways. Previously we demonstrated that a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the baculovirus envelope glycoprotein GP64 (GP64-FIV) efficiently transduced mouse nasal epithelia in vivo but transduced mouse intrapulmonary airways with 10-fold less efficiency. Here, we demonstrate that members of a family of proteins with antiviral activity, interferon-induced transmembrane proteins (IFITMs), are more highly expressed in mouse intrapulmonary airways as compared with mouse nasal airways. Using GP64- and VSV-G (vesicular stomatitis virus G glycoprotein) pseudotyped FIV, we show that expression of mouse IFITM1, IFITM2, and IFITM3 restricts gene transfer. Further, we show that both the nasal and intrapulmonary airways of IFITM locus knockout mice are more efficiently transduced with GP64 FIV than their heterozygous littermates. In anticipation of transitioning our studies into pig models of airway disease and clinical trials in humans, we investigated the ability of pig and human IFITMs to restrict lentiviral gene transfer. We observed that both human and pig IFITMs partially restricted both VSV-G-FIV and GP64-FIV transduction in vitro. Previous studies have focused on IFITM-mediated restriction of replication-competent wild-type viruses; however, these results implicate the IFITM proteins as restriction factors that can limit lentivirus-based vector gene transfer to airway epithelia. The findings are relevant to future preclinical and clinical airway gene therapy trials using lentivirus-based vectors. PMID- 27004833 TI - Inconsistency in hemodynamic characterization of severe aortic stenosis: MRI studies are needed! PMID- 27004835 TI - Dental and skeletal effects of palatal expansion techniques: a systematic review of the current evidence from systematic reviews and meta-analyses. AB - The aim was to assess the quality and to summarise the findings of the Systematic Reviews (SRs) and Meta-Analyses (MAs) on the dental and skeletal effects of maxillary expansion. Electronic and manual searches have been independently conducted by two investigators, up to February 2015. SRs and MAs on the dentoalveolar and skeletal effects of fixed expanders were included. The methodological quality was assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews). The design of the primary studies included in each SR/MA was assessed with the LRD (Level of Research Design scoring). The evidence for each outcome was rated applying a pre-determined scale. Twelve SRs/MAs were included. The AMSTAR scores ranged from 4 to 10. Two SRs/MAs included only RCTs. The current findings from SRs/MAs support with high evidence a significant increase in the short-term of maxillary dentoalveolar transversal dimensions after Rapid Maxillary Expansion (RME). The same effect is reported with moderate evidence after Slow Maxillary Expansion (SME). However, there is moderate evidence of a non-significant difference between the two expansion modalities concerning the short-term dentoalveolar effects. With both RME and SME, significant increase of skeletal transversal dimension in the short-term is reported, and the skeletal expansion is always smaller than the dentoalveolar. Even though dental relapse to some extent is present, long-term results of the dentoalveolar effects show an increase of the transversal dimension, supported by moderate evidence for RME and low evidence for SME. Skeletal long-term effects are reported only with RME, supported by very low evidence. PMID- 27004834 TI - Tick-borne bacterial pathogens in southwestern Finland. AB - BACKGROUND: Ixodes ricinus and Ixodes persulcatus are the main vectors of Lyme borreliosis spirochetes and several other zoonotic bacteria in northern Europe and Russia. However, few studies screening bacterial pathogens in Finnish ticks have been conducted. Therefore, reports on the occurrence and prevalence of several bacterial pathogens detected from ticks elsewhere in Europe and Russia are altogether missing from Finland. The main aim of the current study was to produce novel data on the occurrence and prevalence of several tick-borne bacterial pathogens in ticks collected from southwestern Finland. METHODS: Ticks were collected in 2013-2014 by blanket dragging from 25 localities around southwestern Finland, and additionally from a dog in Lempaala. Collected ticks were molecularly identified and screened for Borrelia burgdorferi s.l., Borrelia miyamotoi, Rickettsia, Bartonella and Candidatus Neoehrlichia mikurensis using quantitative PCR. Furthermore, detected Rickettsia spp. were sequenced using conventional PCR to determine species. RESULTS: A total of 3169 ticks in 1174 DNA samples were screened for the listed pathogens. The most common bacteria detected was B. burgdorferi (s.l.) (18.5 % nymphal and 23.5 % adult ticks), followed by Rickettsia spp. (1.1 %; 5.1 %) and B. miyamotoi (0.51 %; 1.02 %). B. miyamotoi and Rickettsia spp. were also detected in larval samples (minimum infection rates 0.31 % and 0.21 %, respectively). Detected Rickettsia spp. were identified by sequencing as R. helvetica and R. monacensis. All screened samples were negative for Bartonella spp. and Ca. N. mikurensis. CONCLUSIONS: In the current study we report for the first time the presence of Rickettsia in Finnish ticks. Furthermore, Rickettsia spp. and B. miyamotoi were found from larval tick samples, emphasizing the importance they may have as vectors of these pathogens. Comparisons of tick density estimates and B. burgdorferi (s.l.) prevalence made between the current study and a previous study conducted in 2000 in ten out of the 25 study localities suggest that an increase in tick abundance and B. burgdorferi (s.l.) prevalence has occurred in at least some of the study localities. PMID- 27004836 TI - Isolation of Enterobacter aerogenes carrying blaTEM-1 and blaKPC-3 genes recovered from a hospital Intensive Care Unit. AB - Enterobacter aerogenes has recently emerged as an important hospital pathogen. In this study, we showed the emergence of E. aerogenes isolates carrying the blaKPC gene in patients colonized by carbapenem-resistant Klebsiella pneumoniae strains. Two multiresistant E. aerogenes isolates were recovered from bronchial aspirates of two patients hospitalized in the Intensive Care Unit at the "Santa Maria della Scaletta" Hospital, Imola. The antimicrobial susceptibility test showed the high resistance to carbapenems and double-disk synergy test confirmed the phenotype of KPC and AmpC production. Other investigation revealed that ESBL and blaKPC genes were carried on the conjugative pKpQIL plasmid. This is a relevant report in Italy that describes a nosocomial infection due to the production of KPC beta lactamases by an E. aerogenes isolate in patients previously colonized by K. pneumoniae carbapenem-resistant. In conclusion, it's necessary a continuous monitoring of multidrug-resistant strains for the detection of any KPC-producing bacteria that could expand the circulation of carbapenem-resistant pathogens. PMID- 27004837 TI - RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy. AB - Studies have demonstrated a relationship between clinical outcomes after curative resection for colorectal cancer (CRC) and gene mutations of the EGFR pathway; however, no studies have examined metastatic CRC (mCRC) patients with metastasectomy. The aim of this study was to evaluate the relationship between gene mutations of EGFR pathway and clinical outcomes after metastasectomy in mCRC patients. A total of 1,053 patients histopathologically confirmed CRC received a genotyping test for the EGFR pathway from February 2012 to October 2013. Detailed information was obtained through review of medical records. Gene mutations of EGFR pathway were analyzed by Luminex assay. Overall survival (OS) and recurrence free survival were estimated by the Kaplan-Meier method and the log-rank test was used to compare the survival outcomes by gene mutation status. A total of 132 patients received metastasectomy. The frequencies of KRAS exon 2, KRAS exon 3.4, NRAS, BRAF, and PIK3CA mutations were 38.6% (51/132), 3.6% (5/132), 5.1% (7/132), 5.1% (7/132), and 8.7% (12/132), respectively. With a median follow-up of 84.1 months (57.2-NA) for a survivor, the 4-year OS rate was 65.6% for mCRC with RAS mutation, and 81.3% for mCRC with wild-type RAS (p < 0.05). We observed a statistically significant correlation for only the RAS mutation and OS. In multivariate analysis, RAS mutation and liver metastasis were independent factors for shorter OS. There were no significant differences between gene mutations of EGFR pathway and recurrence free survival. RAS mutation in mCRC metastasectomy patients was associated with shorter overall survival. PMID- 27004838 TI - Primary care providers' experiences caring for complex patients in primary care: a qualitative study. AB - BACKGROUND: Complex patients are increasingly common in primary care and often have poor clinical outcomes. Healthcare system barriers to effective care for complex patients have been previously described, but less is known about the potential impact and meaning of caring for complex patients on a daily basis for primary care providers (PCPs). Our objective was to describe PCPs' experiences providing care for complex patients, including their experiences of health system barriers and facilitators and their strategies to enhance provision of effective care. METHODS: Using a general inductive approach, our qualitative research study was guided by an interpretive epistemology, or way of knowing. Our method for understanding included semi-structured in-depth interviews with internal medicine PCPs from two university-based and three community health clinics. We developed an interview guide, which included questions on PCPs' experiences, perceived system barriers and facilitators, and strategies to improve their ability to effectively treat complex patients. To focus interviews on real cases, providers were asked to bring de-identified clinical notes from patients they considered complex to the interview. Interview transcripts were coded and analyzed to develop categories from the raw data, which were then conceptualized into broad themes after team-based discussion. RESULTS: PCPs (N = 15) described complex patients with multidimensional needs, such as socio-economic, medical, and mental health. A vision of optimal care emerged from the data, which included coordinating care, preventing hospitalizations, and developing patient trust. PCPs relied on professional values and individual care strategies to overcome local and system barriers. Team based approaches were endorsed to improve the management of complex patients. CONCLUSIONS: Given the barriers to effective care described by PCPs, individual PCP efforts alone are unlikely to meet the needs of complex patients. To fulfill PCP's expressed concepts of optimal care, implementation of effective systemic approaches should be considered. PMID- 27004839 TI - Does the modified Glasgow Prognostic Score (mGPS) have a prognostic role in esophageal cancer? AB - BACKGROUND: The modified Glasgow Prognostic Score (mGPS), which combines indices of decreased plasma albumin and elevated CRP, has reported independent prognostic significance in colorectal cancer, but its value in upper gastrointestinal cancer is unclear. The aim of this study was to assess the prognostic significance of mGPS in patients with operable esophageal malignancy. METHODS: Patients undergoing resection with curative intent between January 2008 and June 2013 were included. The mGPS was scored as 0, 1, or 2 based on CRP(>10 mg/L) and albumin(<35g/L). The mGPS score (0 vs. 1/2 combined) was correlated with patient and tumor characteristics, and operative and oncologic outcomes. RESULTS: Two hundred and twenty-three patients were included. Median (range) follow-up was 21(12-70) months. The mGPS was 0 in 174 patients(78%). mGPS was significantly associated with positive nodal status(P = 0.008) and stage >=III (P = 0.017). There was a significant improvement in overall survival in patients with mGPS = 0 (47.8 vs. 37.5 months, P = 0.014) but in multivariate analysis, only TNM-stage and nodal status were found to be independent prognostic indicators. CONCLUSIONS: mGPS is associated with advanced stage but has no independent prognostic significance and does not impact on operative outcomes. Consequently, this data does not support its routine application in patient selection or prognostication. J. Surg. Oncol. 2016;113:732-737. (c) 2016 Wiley Periodicals, Inc. PMID- 27004841 TI - Clinical use of whole genome sequencing for Mycobacterium tuberculosis. AB - Drug-resistant tuberculosis (TB) remains a major challenge to global health and to healthcare in the UK. In 2014, a total of 6,520 cases of TB were recorded in England, of which 1.4 % were multidrug-resistant TB (MDR-TB). Extensively drug resistant TB (XDR-TB) occurs at a much lower rate, but the impact on the patient and hospital is severe. Current diagnostic methods such as drug susceptibility testing and targeted molecular tests are slow to return or examine only a limited number of target regions, respectively. Faster, more comprehensive diagnostics will enable earlier use of the most appropriate drug regimen, thus improving patient outcomes and reducing overall healthcare costs. Whole genome sequencing (WGS) has been shown to provide a rapid and comprehensive view of the genotype of the organism, and thus enable reliable prediction of the drug susceptibility phenotype within a clinically relevant timeframe. In addition, it provides the highest resolution when investigating transmission events in possible outbreak scenarios. However, robust software and database tools need to be developed for the full potential to be realized in this specialized area of medicine. PMID- 27004840 TI - Small vessel disease and cognitive impairment: The relevance of central network connections. AB - Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non-central brain network connections. Brain networks were reconstructed from diffusion-weighted MRI scans in 72 individuals (75 +/- 8 years) with cognitive impairment and SVD on MRI. The centrality of white matter connections in the network was defined using graph theory. The association between the fractional anisotropy (FA) of central versus non-central connections, executive functioning, and markers of SVD was evaluated with linear regression and mediation analysis. Lower FA in central network connections was more strongly associated with impairment in executive functioning than FA in non-central network connections (r = 0.41 vs. r = 0.27; P < 0.05). Results were consistent across varying thresholds to define the central subnetwork (>50%-10% connections). Higher SVD burden was associated with lower FA in central as well as non-central network connections. However, only central network FA mediated the relationship between white matter hyperintensity volume and executive functioning [change in regression coefficient after mediation (95% CI): -0.15 (-0.35 to -0.02)]. The mediation effect was not observed for FA alterations in non-central network connections [-0.03 (-0.19 to 0.04)]. These findings suggest that the centrality of network connections, and thus their contribution to global network efficiency, appears to be relevant for understanding the relationship between SVD and cognitive impairment. Hum Brain Mapp 37:2446-2454, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004842 TI - Does gender moderate the relationship between polydrug use and sexual risk-taking among Australian secondary school students under 16 years of age? AB - INTRODUCTION AND AIMS: This study examines the association of alcohol and polydrug use with risky sexual behaviour in adolescents under 16 years of age and if this association differs by gender. DESIGN AND METHODS: The sample consisted of 5412 secondary school students under 16 years of age from Victoria, Australia. Participants completed an anonymous and confidential survey during class time. The key measures were having had sex before legal age of consent (16 years), unprotected sex before 16 (no condom) and latent-class derived alcohol and polydrug use variables based on alcohol, tobacco, cannabis, inhalants and other illegal drug use in the past month. RESULTS: There were 7.52% and 2.55% of adolescents who reported having sex and having unprotected sex before 16 years of age, respectively. After adjusting for antisocial behaviours, peers' drug use and family and school risk factors, girls were less likely to have unprotected sex (odds ratio = 0.31, P = 0.003). However, the interaction of being female and polydrug use (odds ratio = 4.52, P = 0.004) was significant, indicating that girls who engaged in polydrug use were at higher risk of having unprotected sex. For boys, the effect of polydrug use was non-significant (odds ratio = 1.44, P = 0.310). Discussion and Conclusions For girls, polydrug use was significantly associated with unprotected sex after adjusting for a range of risk factors, and this relationship was non-significant for boys. Future prevention programs for adolescent risky sexual behaviour and polydrug use might benefit from a tailored approach to gender differences. [Chan GCK, Kelly AB, Hides L, Quinn C, Williams JW. Does gender moderate the relationship between polydrug use and sexual risk taking among Australian secondary school students under 16 years of age? Drug Alcohol Rev 2016;35:750-754]. PMID- 27004843 TI - Prevalence of thyroid dysfunction and thyroid antibodies in a private obstetrical practice in Sydney. AB - BACKGROUND: Hypothyroidism in pregnancy is associated with adverse obstetrical events and neurodevelopmental disorders in infants. The prevalence of thyroid dysfunction during pregnancy in Australia is not well documented, and universal screening remains questionable. AIM: To assess the prevalence of thyroid dysfunction and positive thyroid antibodies and review the indications for universal screening of thyroid function in pregnancy. MATERIALS AND METHODS: The prospective observational study was undertaken between 2009 and 2014. Thyroid stimulating hormone (TSH), free thyroxine (FT4) levels, thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) were measured in 1069 women at booking-in. RESULTS: One hundred and three women, (9.6%), exhibited subclinical hypothyroidism, with TSH levels >2.5mIU/l. Eighty-seven women (8.1%) had TSH levels > 2.5 and <=5 mIU/l. Of these, 41.4% (36 patients) were positive for TPOAb. Twelve women (1.5%) had a TSH >5 and <=10 mIU/l with 66.7% (8 patients) positive for TPOAb. Four patients (0.4%) had a TSH level >10 mIU/l with 50% (2 patients) positive for TPOAb. Positive thyroid antibodies were detected in 258 patients (24.13%). Although statistically significant, the rank correlations between TSH and TPOAb (r = 0.08, P = 0.023) and TgAb (r = -0.081, P = 0.021) were weak. Similarly, weak rank correlations were observed between TSH and age (r = 0.095), parity (r = -0.081) and weight (r = 0.089). CONCLUSION: A high prevalence of subclinical hypothyroidism and positive thyroid antibodies exists in this cohort, as well as unsuspected chemical hypothyroidism, providing a strong case for universal screening with TSH and the consideration of thyroid antibody testing of all Australian pregnant women. PMID- 27004844 TI - Intraparticulate speciation analysis of soft nanoparticulate metal complexes. The impact of electric condensation on the binding of Cd2+/Pb2+/Cu2+ by humic acids. AB - In aqueous dispersions of soft, charged nanoparticles, the physicochemical conditions prevailing within the particle body generally differ substantially from those in the bulk medium. Accordingly it is necessary to define intrinsic descriptors that appropriately reflect the chemical speciation inside the particle's microenvironment. Herein the speciation of divalent metal ions within the body of negatively charged soft nanoparticulate complexants is elaborated for the example case of humic acid association with Cd(ii), Pb(ii) and Cu(ii). The electrostatic effects are described by a two-state model that accounts for counterion condensation in the intraparticulate double layer shell at the particle/medium interface and Donnan partitioning within the bulk of the particle body. Inner-sphere complex formation is defined by an intrinsic binding constant expressed in terms of local reactant concentrations as controlled by the pertinent electrostatic conditions. For the high particle charge density case (Debye length smaller than charged site separation), three distinct intraparticulate metal species are identified, namely free hydrated ions, electrostatically condensed ions, and inner-sphere metal-humic complexes. For all metal ions studied, the electrostatic contribution to the association of the metal ion with the oppositely charged particle is found to account for a substantial fraction of the total metal bound. PMID- 27004845 TI - Genetic diversity among human parainfluenza virus type 2 isolated in Croatia between 2011 and 2014. AB - The dynamics and evolution of the human parainfluenza virus type 2 (HPIV2) in Croatia, and also globally, are largely unknown. Most HPIV2 infections are treated symptomatically outside the hospital setting. Thus, the diagnosis is missing making it difficult to follow the genetic variation and evolution of the HPIV2. This study explores hospitalized HPIV2 cases in Croatia during 4-year period (2011-2014). Most cases in this period were reported in October or November (68.75%) and most of patients were under 2 years of age (81.25%). For molecular analyses, we used the F and HN gene sequences and showed that although both regions are equally suitable for phylogenetic analyses it would be advantageous to use regions longer than 2 kb for HPIV2 analyses of isolates which are spatially and temporally closely related. We show here that the dominant cluster in this area was cluster G3 while only one strain isolated in this period was positioned in the distant cluster G1a. Further monitoring of the HPIV2 will determine whether cluster G3 will remain dominant or it will be overruled by cluster G1a. This will be important for the surveillance of virus circulation in population and significance of the viral infection. J. Med. Virol. 88:1733-1741, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004846 TI - Standard deviation of carotid young's modulus and presence or absence of plaque improves prediction of coronary heart disease risk. AB - INTRODUCTION: The stiffness of large arteries and the presence or absence of plaque are associated with coronary heart disease (CHD). Because arterial walls are biologically heterogeneous, the standard deviation of Young's modulus (YM std) of the large arteries may better predict coronary atherosclerosis. However, the role of YM-std in the occurrence of coronary events has not been addressed so far. Therefore, this study investigated whether the carotid YM-std and the presence or absence of plaque improved CHD risk prediction. METHODS: One hundred and three patients with CHD (age 66 +/- 11 years) and 107 patients at high risk of atherosclerosis (age 61 +/- 7 years) were recruited. Carotid YM was measured by the vessel texture matching method, and YM-std was calculated. Carotid intima media thickness was measured by the MyLab 90 ultrasound Platform employed dedicated software RF-tracking technology. RESULTS: In logistic regression analysis, YM-std (OR = 1.010; 95% CI = 1.003-1.016), carotid plaque (OR = 16.759; 95% CI = 3.719-75.533) and YM-std plus plaque (OR = 0.989; 95% CI = 0.981-0.997) were independent predictors of CHD. The traditional risk factors (TRF) plus YM std plus plaque model showed a significant improvement in area under the receiver operating characteristic curve (AUC), which increased from 0.717 (TRF only) to 0.777 (95% CI for the difference in adjusted AUC: 0.010-0.110). CONCLUSIONS: Carotid YM-std is a powerful independent predictor of CHD. Adding plaque and YM std to TRF improves CHD risk prediction. PMID- 27004847 TI - Advanced dementia: opinions of physicians and nurses about antibiotic therapy, artificial hydration and nutrition in patients with different life expectancies. AB - AIM: The aim of the present study was to investigate the proportion of physicians and nurses who agree with the administration of antibiotic therapy (AT), artificial hydration (AH), and artificial nutrition (AN) in patients with advanced dementia and different life expectancies. Furthermore, we aimed at analyzing the correlates of the opinion according to which medical treatments should no longer be given to advanced dementia patients once their life expectancy falls. METHODS: End-of-life decisions and opinions were measured with a questionnaire that was sent to geriatric units, hospices and nursing homes in three different regions of Italy. Multivariate logistic regressions were carried out to ascertain the correlates of the agreement with the administration of AH, AT or AN. RESULTS: When the patient's life expectancy was 1-6 months, 83% of respondents agreed with AH, 79% with AT and 71% with AN. When the life expectancy was less than 1 month, a large proportion of respondents still agreed with AH and AT (73% and 61%), whereas less than one in two respondents (48%) agreed with AN. CONCLUSIONS: The findings of the present study showed that AN creates more ethical dilemmas in the clinical management of end of life than other treatments, such as AH or AT. Opinions on whether or not these practices are appropriate at the end of life were related with feelings, thoughts and ethical issues that played a different part for physicians and nurses. Geriatr Gerontol Int 2017; 17: 487-493. PMID- 27004848 TI - Salusin-beta induces foam cell formation and monocyte adhesion in human vascular smooth muscle cells via miR155/NOX2/NFkappaB pathway. AB - Vascular smooth muscle cells (VSMCs) are indispensible components in foam cell formation. Salusin-beta is a stimulator in the progression of atherosclerosis. Here, we showed that salusin-beta increased foam cell formation evidenced by accumulation of lipid droplets and intracellular cholesterol content, and promoted monocyte adhesion in human VSMCs. Salusin-beta increased the expressions and activity of acyl coenzyme A:cholesterol acyltransferase-1 (ACAT-1) and vascular cell adhesion molecule-1 (VCAM-1) in VSMCs. Silencing of ACAT-1 abolished the salusin-beta-induced lipid accumulation, and silencing of VCAM-1 prevented the salusin-beta-induced monocyte adhesion in VSMCs. Salusin-beta caused p65-NFkappaB nuclear translocation and increased p65 occupancy at the ACAT 1 and VCAM-1 promoter. Inhibition of NFkappaB with Bay 11-7082 prevented the salusin-beta-induced ACAT-1 and VCAM-1 upregulation, foam cell formation and monocyte adhesion in VSMCs. Scavenging ROS, inhibiting NADPH oxidase or knockdown of NOX2 abolished the effects of salusin-beta on ACAT-1 and VCAM-1 expressions, p65-NFkappaB nuclear translocation, lipid accumulation and monocyte adhesion in VSMCs. Salusin-beta increased miR155 expression, and knockdown of miR155 prevented the effects of salusin-beta on ACAT-1 and VCAM-1 expressions, p65 NFkappaB nuclear translocation, lipid accumulation, monocyte adhesion and ROS production in VSMCs. These results indicate that salusin-beta induces foam formation and monocyte adhesion via miR155/NOX2/NFkappaB-mediated ACAT-1 and VCAM 1 expressions in VSMCs. PMID- 27004849 TI - Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer. AB - The molecular basis of aberrant protein glycosylation, a pathological alteration widespread in colorectal cancers (CRC), and the mechanisms by which it contributes to tumor progression remain largely unknown. We performed targeted re sequencing of 430 glycosylation-associated genes in a series of patient-derived CRC cell lines (N = 31) and matched primary tumor tissues, identifying 12 new significantly mutated glycosylation-associated genes in colon cancer. In particular, we observed an enrichment of mutations in genes (B3GNT2, B4GALT2, ST6GALNAC2) involved in the biosynthesis of N- and Cores 1-3 O-linked glycans in the colon, accounting for ~16% of the CRCs tested. Analysis of independent large scale tumor tissue datasets confirmed recurrent mutations within these genes in colon and other gastrointestinal cancers. Systematic biochemical and phenotypic characterization of the candidate wild-type and mutant glycosyltransferases demonstrated these mutations as either markedly altering protein localization, post-translational modification, encoded enzymatic activities and/or the migratory potential of colon carcinoma cells. These findings suggest that functionally deleterious mutations in glycosyltransferase genes in part underlie aberrant glycosylation, and contribute to the pathogenesis of molecular subsets of colon and other gastrointestinal malignancies. PMID- 27004853 TI - Communication: Enhanced chemical reactivity of graphene on a Ni(111) substrate. AB - Due to the unique combination of structural, mechanical, and transport properties, graphene has emerged as an exceptional candidate for catalysis applications. The low chemical reactivity caused by sp(2) hybridization and strongly delocalized pi electrons, however, represents a main challenge for straightforward use of graphene in its pristine, free-standing form. Following recent experimental indications, we show that due to charge hybridization, a Ni(111) substrate can enhance the chemical reactivity of graphene, as exemplified by the interaction with the CO molecule. While CO only physisorbs on free standing graphene, chemisorption of CO involving formation of ethylene dione complexes is predicted in Ni(111)-graphene. Higher chemical reactivity is also suggested in the case of oxidized graphene, opening the way to a simple and efficient control of graphene chemical properties, devoid of complex defect patterning or active metallic structures deposition. PMID- 27004852 TI - Structure-based screening and optimization of cytisine derivatives as inhibitors of the menin-MLL interaction. AB - The natural product-like compound 1 was identified as a direct inhibitor of the menin-MLL interaction by in silico screening. Structure-based optimization furnished analogue 1a, which showed significantly higher potency than both the lead structure 1 and the reference compound MI-2. PMID- 27004850 TI - Amyloid formation of growth hormone in presence of zinc: Relevance to its storage in secretory granules. AB - Amyloids are cross-beta-sheet fibrillar aggregates, associated with various human diseases and native functions such as protein/peptide hormone storage inside secretory granules of neuroendocrine cells. In the current study, using amyloid detecting agents, we show that growth hormone (GH) could be stored as amyloid in the pituitary of rat. Moreover, to demonstrate the formation of GH amyloid in vitro, we studied various conditions (solvents, glycosaminoglycans, salts and metal ions) and found that in presence of zinc metal ions (Zn(II)), GH formed short curvy fibrils. The amyloidogenic nature of these fibrils was examined by Thioflavin T binding, Congo Red binding, transmission electron microscopy and X ray diffraction. Our biophysical studies also suggest that Zn(II) initiates the early oligomerization of GH that eventually facilitates the fibrillation process. Furthermore, using immunofluorescence study of pituitary tissue, we show that GH in pituitary significantly co-localizes with Zn(II), suggesting the probable role of zinc in GH aggregation within secretory granules. We also found that GH amyloid formed in vitro is capable of releasing monomers. The study will help to understand the possible mechanism of GH storage, its regulation and monomer release from the somatotrophs of anterior pituitary. PMID- 27004851 TI - N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release. AB - Cortical spreading depression (CSD), a wave of neuronal depolarization in the cerebral cortex following traumatic brain injury or cerebral ischemia, significantly aggravates brain damage. Here, we tested whether N palmitoylethanolamine (PEA), a substance that effectively reduces lesion volumes and neurological deficits after ischemic stroke, influences CSD. CSD was elicited chemically in adult rats and occurrence, amplitude, duration and propagation velocity of CSD was determined prior to and for 6 hours after intraperitoneal injection of PEA. The chosen systemic administration of PEA stabilized the amplitude of CSD for at least four hours and prevented the run-down of amplitudes that is typically observed and was also seen in untreated controls. The propagation velocity of the CSD waves was unaltered indicating stable neuronal excitability. The stabilization of CSD amplitudes by PEA indicates that inhibition or prevention of CSD does not underlie PEA's profound neuroprotective effect. Rather, PEA likely inhibits proinflammatory cytokine release thereby preventing the run-down of CSD amplitudes. This contribution of PEA to the maintenance of neuronal excitability in healthy tissue during CSD potentially adds to neuroprotection outside a damaged area, while other mechanisms control PEA-mediated neuroprotection in damaged tissue resulting from traumatic brain injury or cerebral ischemia. PMID- 27004854 TI - Communication: An accurate calculation of the S1 C2H2 cis-trans isomerization barrier height. AB - A high level ab initio calculation of the cis-trans isomerization barrier height in the first excited singlet electronic state of acetylene is found to agree very well with a recent experimental determination. PMID- 27004855 TI - Communication: The formation of CHe(2+) by radiative association. AB - The detection of ArH(+) has revived the interest in the search for noble gas containing species. Despite helium being the second most abundant element in the universe (He/H ~ 1/10), it has never been observed in any other form than that of a neutral/ionized atom in the interstellar medium. Because He is the "most noble" gas, its non-observation as part of neutral molecular systems is understandable. It is more surprising for charged species, especially HeH(+) whose spectral signatures are well documented in the laboratory. The purpose of this work was to find a simple positive ion containing He, and likely to be observed as an alternative to undetected HeH(+). Among the HeX(2+) diatomics formed with first row atoms, we focused on X = C because of both its relative abundance and the magnitude of its ionization potentials with respect to He. The formation of CHe(2+) by radiative association is the center of this study. The question was addressed by means of numerical simulations using high level ab initio calculations of the CHe(2+) potential surface, followed by a quantum chemical determination of the rate coefficients for the corresponding radiative association in the range of 10 to 1000K. The radiative association path shows a potential well deep enough to accommodate 20 vibrational levels, and no barrier to oppose the reaction. The rate coefficient varies from ~4.5 * 10(-20) cm(3)s( 1) to ~2.5 * 10(-22) cm(3)s(-1) for the temperatures considered. The present study suggests that the existence of this species has to be searched for mainly in highly irradiated regions. PMID- 27004856 TI - A theoretical investigation of symmetry-origin unidirectional energy gradient in light-harvesting dendrimers. AB - We theoretically investigate a possibility that the symmetry of the repetitively branched structure of light-harvesting dendrimers creates the energy gradient descending toward inner generations (layers of pigment molecules) of the dendrimers. In the first half of this paper, we define a model system using the Frenkel exciton Hamiltonian that focuses only on the topology of dendrimers and numerically show that excitation energy tends to gather at inner generations of the model system at a thermal equilibrium state. This indicates that an energy gradient is formed in the model system. In the last half, we attribute this result to the symmetry of the model system and propose two symmetry-origin mechanisms creating the energy gradient. The present analysis and proposition are based on the theory of the linear chain (LC) decomposition [S. Koda, J. Chem. Phys. 142, 204112 (2015)], which equivalently transforms the model system into a set of one-dimensional systems on the basis of the symmetry of dendrimers. In the picture of the LC decomposition, we find that energy gradient is formed both in each linear chain and among linear chains, and these two mechanisms explain the numerical results well. PMID- 27004857 TI - Quantum dynamics of electronic transitions with Gauss-Hermite wave packets. AB - A new methodology based on the superposition of time-dependent Gauss-Hermite wave packets is developed to describe the wave function of a system in which several interacting electronic states are coupled to a bath of harmonic oscillators. The equations of motion for the wave function parameters are obtained by employing the Dirac-Frenkel time-dependent variational principle. The methodology is applied to study the quantum dynamical behaviour of model systems with two interacting electronic states characterized by a relatively large reorganization energy and a range of energy biases. The favourable scaling properties make it a promising tool for the study of the dynamics of chemico-physical processes in molecular systems. PMID- 27004859 TI - The effect of basis set and exchange-correlation functional on time-dependent density functional theory calculations within the Tamm-Dancoff approximation of the x-ray emission spectroscopy of transition metal complexes. AB - The simulation of X-ray emission spectra of transition metal complexes with time dependent density functional theory (TDDFT) is investigated. X-ray emission spectra can be computed within TDDFT in conjunction with the Tamm-Dancoff approximation by using a reference determinant with a vacancy in the relevant core orbital, and these calculations can be performed using the frozen orbital approximation or with the relaxation of the orbitals of the intermediate core ionised state included. Both standard exchange-correlation functionals and functionals specifically designed for X-ray emission spectroscopy are studied, and it is shown that the computed spectral band profiles are sensitive to the exchange-correlation functional used. The computed intensities of the spectral bands can be rationalised by considering the metal p orbital character of the valence molecular orbitals. To compute X-ray emission spectra with the correct energy scale allowing a direct comparison with experiment requires the relaxation of the core-ionised state to be included and the use of specifically designed functionals with increased amounts of Hartree-Fock exchange in conjunction with high quality basis sets. A range-corrected functional with increased Hartree-Fock exchange in the short range provides transition energies close to experiment and spectral band profiles that have a similar accuracy to those from standard functionals. PMID- 27004858 TI - Reaction mechanism and reaction coordinates from the viewpoint of energy flow. AB - Reaction coordinates are of central importance for correct understanding of reaction dynamics in complex systems, but their counter-intuitive nature made it a daunting challenge to identify them. Starting from an energetic view of a reaction process as stochastic energy flows biased towards preferred channels, which we deemed the reaction coordinates, we developed a rigorous scheme for decomposing energy changes of a system, both potential and kinetic, into pairwise components. The pairwise energy flows between different coordinates provide a concrete statistical mechanical language for depicting reaction mechanisms. Application of this scheme to the C7eq -> C7ax transition of the alanine dipeptide in vacuum revealed novel and intriguing mechanisms that eluded previous investigations of this well studied prototype system for biomolecular conformational dynamics. Using a cost function developed from the energy decomposition components by proper averaging over the transition path ensemble, we were able to identify signatures of the reaction coordinates of this system without requiring any input from human intuition. PMID- 27004860 TI - Collision-induced Raman scattering from a pair of dissimilar particles: An intriguing mathematical model predicting the suppression of the odd-numbered partial waves. AB - Relying on a simple analytic two-atom model in which the anisotropy of the interaction dipole polarizability obeys an inverse power law as a function of separation, we offer mathematical and numerical evidence that, in a monoatomic gas, the free-free Raman spectrum for a collisional pair of two different isotopes, a-a', may vastly differ from that for a-a. This result is obtained even if a and a' are assumed to have the same mass and zero nuclear spin and even if a a and a-a' are subject to the same interaction polarizability and potential. The mechanism responsible for this effect is inherent in the parity of the partial wave rotational quantum number J: given that the contribution of each partial wave to the Raman cross section is controlled by a polarizability-transition matrix-element and that each of those matrix-elements has a radial component with a magnitude slightly smaller than that of the preceding partial wave, a deficit which disfavors the odd-numbered waves is accumulated upon summing over J. In the far high-frequency wing, this deficit tends to generate spectral intensities for a-a' about half as great as the a-a ones, a tendency which becomes all the more effective as temperature is decreased. We show for instance that, for the spectral branch DeltaJ = 2, the fractional difference between the free-free differential cross sections for a-a and a-a' is 12(1-x(2))(3)1+3x(4), with x=?[E/E(')] (E (E') being the initial (final) state energy of the pair and E' - E = hcnu (nu > 0)). Remarkably, this quantity is zero at nu ~ 0 but goes to 12 for nu ? 0. For DeltaJ = 0, analogous conclusions may be drawn from the expression (1+ln(1+x1-x)2arctanx)(-1). PMID- 27004862 TI - Defining the contributions of permanent electrostatics, Pauli repulsion, and dispersion in density functional theory calculations of intermolecular interaction energies. AB - In energy decomposition analysis of Kohn-Sham density functional theory calculations, the so-called frozen (or pre-polarization) interaction energy contains contributions from permanent electrostatics, dispersion, and Pauli repulsion. The standard classical approach to separate them suffers from several well-known limitations. We introduce an alternative scheme that employs valid antisymmetric electronic wavefunctions throughout and is based on the identification of individual fragment contributions to the initial supersystem wavefunction as determined by an energetic optimality criterion. The density deformations identified with individual fragments upon formation of the initial supersystem wavefunction are analyzed along with the distance dependence of the new and classical terms for test cases that include the neon dimer, ammonia borane, water-Na(+), water-Cl(-), and the naphthalene dimer. PMID- 27004861 TI - Derivation of instanton rate theory from first principles. AB - Instanton rate theory is used to study tunneling events in a wide range of systems including low-temperature chemical reactions. Despite many successful applications, the method has never been obtained from first principles, relying instead on the "Im F" premise. In this paper, the same expression for the rate of barrier penetration at finite temperature is rederived from quantum scattering theory [W. H. Miller, S. D. Schwartz, and J. W. Tromp, J. Chem. Phys. 79, 4889 (1983)] using a semiclassical Green's function formalism. This justifies the instanton approach and provides a route to deriving the rate of other processes. PMID- 27004863 TI - Quantum tunneling splittings from path-integral molecular dynamics. AB - We illustrate how path-integral molecular dynamics can be used to calculate ground-state tunnelling splittings in molecules or clusters. The method obtains the splittings from ratios of density matrix elements between the degenerate wells connected by the tunnelling. We propose a simple thermodynamic integration scheme for evaluating these elements. Numerical tests on fully dimensional malonaldehyde yield tunnelling splittings in good overall agreement with the results of diffusion Monte Carlo calculations. PMID- 27004864 TI - Calculating splittings between energy levels of different symmetry using path integral methods. AB - It is well known that path-integral methods can be used to calculate the energy splitting between the ground and the first excited state. Here we show that this approach can be generalized to give the splitting patterns between all the lowest energy levels from different symmetry blocks that lie below the first-excited totally symmetric state. We demonstrate this property numerically for some two dimensional models. The approach is likely to be useful for computing rovibrational energy levels and tunnelling splittings in floppy molecules and gas phase clusters. PMID- 27004865 TI - Block-diagonalization as a tool for the robust diabatization of high-dimensional potential energy surfaces. AB - Robust diabatization techniques are key for the development of high-dimensional coupled potential energy surfaces (PESs) to be used in multi-state quantum dynamics simulations. In the present study we demonstrate that, besides the actual diabatization technique, common problems with the underlying electronic structure calculations can be the reason why a diabatization fails. After giving a short review of the theoretical background of diabatization, we propose a method based on the block-diagonalization to analyse the electronic structure data. This analysis tool can be used in three different ways: First, it allows to detect issues with the ab initio reference data and is used to optimize the setup of the electronic structure calculations. Second, the data from the block diagonalization are utilized for the development of optimal parametrized diabatic model matrices by identifying the most significant couplings. Third, the block diagonalization data are used to fit the parameters of the diabatic model, which yields an optimal initial guess for the non-linear fitting required by standard or more advanced energy based diabatization methods. The new approach is demonstrated by the diabatization of 9 electronic states of the propargyl radical, yielding fully coupled full-dimensional (12D) PESs in closed form. PMID- 27004866 TI - Understanding the influence of capillary waves on solvation at the liquid-vapor interface. AB - This work investigates the question if surface capillary waves (CWs) affect interfacial solvation thermodynamic properties that determine the propensity of small molecules toward the liquid-vapor interface. We focus on (1) the evaluation of these properties from molecular simulations in a practical manner and (2) understanding them from the perspective of theories in solvation thermodynamics, especially solvent reorganization effects. Concerning the former objective, we propose a computational method that exploits the relationship between an external field acting on the liquid-vapor interface and the magnitude of CWs. The system considered contains the solvent, an externally applied field (f) and the solute molecule fixed at a particular location. The magnitude of f is selected to induce changes in CWs. The difference between the solvation free energies computed in the presence and in the absence of f is then shown to quantify the contribution of CWs to interfacial solvation. We describe the implementation of this method in the canonical ensemble by using a Lennard-Jones solvent and a non-ionic solute. Results are shown for three types of solutes that differ in the nature of short ranged repulsive (hard-core) interactions. Overall, we observe that CWs have a negligible or very small effect on the interfacial solvation free energy of a solute molecule fixed near the liquid-vapor interface for the above systems. We also explain how the effects of pinning or dampening of CWs caused by a fixed solute are effectively compensated and do not contribute to the solvation free energy. PMID- 27004867 TI - Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations. AB - The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B splines to increase the accuracy of the multilevel summation method (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle-mesh Ewald method falls short. PMID- 27004868 TI - Vibrational infrared and Raman spectra of polypeptides: Fragments-in-fragments within molecular tailoring approach. AB - The present work reports the calculation of vibrational infrared (IR) and Raman spectra of large molecular systems employing molecular tailoring approach (MTA). Further, it extends the grafting procedure for the accurate evaluation of IR and Raman spectra of large molecular systems, employing a new methodology termed as Fragments-in-Fragments (FIF), within MTA. Unlike the previous MTA-based studies, the accurate estimation of the requisite molecular properties is achieved without performing any full calculations (FC). The basic idea of the grafting procedure is implemented by invoking the nearly basis-set-independent nature of the MTA based error vis-a-vis the respective FCs. FIF has been tested out for the estimation of the above molecular properties for three isomers, viz., beta strand, 310- and alpha-helix of acetyl(alanine)nNH2 (n = 10, 15) polypeptides, three conformers of doubly protonated gramicidin S decapeptide and trpzip2 protein (PDB id: 1LE1), respectively, employing BP86/TZVP, M06/6-311G**, and M05 2X/6-31G** levels of theory. For most of the cases, a maximum difference of 3 cm( 1) is achieved between the grafted-MTA frequencies and the corresponding FC values. Further, a comparison of the BP86/TZVP level IR and Raman spectra of alpha-helical (alanine)20 and its N-deuterated derivative shows an excellent agreement with the existing experimental spectra. In view of the requirement of only MTA-based calculations and the ability of FIF to work at any level of theory, the current methodology provides a cost-effective solution for obtaining accurate spectra of large molecular systems. PMID- 27004869 TI - Efficient generation of sum-of-products representations of high-dimensional potential energy surfaces based on multimode expansions. AB - The transformation of multi-dimensional potential energy surfaces (PESs) from a grid-based multimode representation to an analytical one is a standard procedure in quantum chemical programs. Within the framework of linear least squares fitting, a simple and highly efficient algorithm is presented, which relies on a direct product representation of the PES and a repeated use of Kronecker products. It shows the same scalings in computational cost and memory requirements as the potfit approach. In comparison to customary linear least squares fitting algorithms, this corresponds to a speed-up and memory saving by several orders of magnitude. Different fitting bases are tested, namely, polynomials, B-splines, and distributed Gaussians. Benchmark calculations are provided for the PESs of a set of small molecules. PMID- 27004870 TI - Triplet excited electronic state switching induced by hydrogen bonding: A transient absorption spectroscopy and time-dependent DFT study. AB - The solvent plays a decisive role in the photochemistry and photophysics of aromatic ketones. Xanthone (XT) is one such aromatic ketone and its triplet triplet (T-T) absorption spectra show intriguing solvatochromic behavior. Also, the reactivity of XT towards H-atom abstraction shows an unprecedented decrease in protic solvents relative to aprotic solvents. Therefore, a comprehensive solvatochromic analysis of the triplet-triplet absorption spectra of XT was carried out in conjunction with time dependent density functional theory using the ad hoc explicit solvent model approach. A detailed solvatochromic analysis of the T-T absorption bands of XT suggests that the hydrogen bonding interactions are different in the corresponding triplet excited states. Furthermore, the contributions of non-specific and hydrogen bonding interactions towards differential solvation of the triplet states in protic solvents were found to be of equal magnitude. The frontier molecular orbital and electron density difference analysis of the T1 and T2 states of XT indicates that the charge redistribution in these states leads to intermolecular hydrogen bond strengthening and weakening, respectively, relative to the S0 state. This is further supported by the vertical excitation energy calculations of the XT methanol supra-molecular complex. The intermolecular hydrogen bonding potential energy curves obtained for this complex in the S0, T1, and T2 states support the model. In summary, we propose that the different hydrogen bonding mechanisms exhibited by the two lowest triplet excited states of XT result in a decreasing role of the npi(*) triplet state, and are thus responsible for its reduced reactivity towards H-atom abstraction in protic solvents. PMID- 27004871 TI - Structural and optical properties of the naked and passivated Al5Au5 bimetallic nanoclusters. AB - The structural and optical properties of both the naked and passivated bimetallic Al5Au5 nanoclusters have been analyzed based on data obtained from ab initio density functional theory and quantum molecular dynamics simulations. It has been found that the Al5Au5 nanocluster possesses a hollow shaped minimum energy structure with segregated Al and Au layered domains, the former representing the electrophilic domain and the latter the nucleophilic domain. In particular, it has been shown that alkali metal cations attach in the nucleophilic domain and hop from one Au site to the next one in the picoseconds time scale, while anions are bound tightly to the Al atoms of the electrophilic domain. Simulating annealing studies are very suggestive of the proneness of the nanocluster towards coalescence into large cluster units, when the cluster is left unprotected by appropriate ligands. Further passivation studies with NaF salt suggest, nonetheless, the possibility of the isolation of the Al5Au5 cluster in molten salts or ionic liquids. PMID- 27004873 TI - State-of-the-art ab initio potential energy curve for the krypton atom pair and thermophysical properties of dilute krypton gas. AB - A new reference krypton-krypton interatomic potential energy curve was developed by means of quantum-chemical ab initio calculations for 36 interatomic separations. Highly accurate values for the interaction energies at the complete basis set limit were obtained using the coupled-cluster method with single, double, and perturbative triple excitations as well as t-aug-cc-pV5Z and t-aug-cc pV6Z basis sets including mid-bond functions, with the 6Z basis set being newly constructed for this study. Higher orders of coupled-cluster terms were considered in a successive scheme up to full quadruple excitations. Core-core and core-valence correlation effects were included. Furthermore, relativistic effects were studied not only at a scalar relativistic level using second-order direct perturbation theory, but also utilizing full four-component and Gaunt-effect computations. An analytical pair potential function was fitted to the interaction energies, which is characterized by a depth of 200.88 K with an estimated standard uncertainty of 0.51 K. Thermophysical properties of low-density krypton were calculated for temperatures up to 5000 K. Second and third virial coefficients were obtained from statistical thermodynamics. Viscosity and thermal conductivity as well as the self-diffusion coefficient were computed using the kinetic theory of gases. The theoretical results are compared with experimental data and with results for other pair potential functions from the literature, especially with those calculated from the recently developed ab initio potential of Waldrop et al. [J. Chem. Phys. 142, 204307 (2015)]. Highly accurate experimental viscosity data indicate that both the present ab initio pair potential and the one of Waldrop et al. can be regarded as reference potentials, even though the quantum-chemical methods and basis sets differ. However, the uncertainties of the present potential and of the derived properties are estimated to be considerably lower. PMID- 27004872 TI - Microwave spectra, molecular structure, and aromatic character of 4a,8a azaboranaphthalene. AB - The microwave spectra for seven unique isotopologues of 4a,8a-azaboranaphthalene [hereafter referred to as BN-naphthalene] were measured using a pulsed-beam Fourier transform microwave spectrometer. Spectra were obtained for the normal isotopologues with (10)B, (11)B, and all unique single (13)C and the (15)N isotopologue (with (11)B), in natural abundance. The rotational, centrifugal distortion and quadrupole coupling constants determined for the (11)B(14)N isotopologue are A = 3042.712 75(43) MHz, B = 1202.706 57(35) MHz, C = 862.220 13(35) MHz, DJ = 0.06(1) kHz, 1.5chiaa ((14)N) = 2.5781(61) MHz, 0.25(chibb - chicc) ((14)N) = - 0.1185(17) MHz, 1.5chiaa (11B) = - 3.9221(75) MHz, and 0.25(chibb - chicc) ((11)B) = - 0.9069(24) MHz. The experimental inertial defect is Delta = - 0.159 amu A(2), which is consistent with a planar structure for the molecule. The B-N bond length from the experimentally determined structure is 1.47 A, which indicates pi-bonding character between the B and N. The measured quadrupole coupling strengths provide important and useful information about the bonding, orbital occupancy, and aromatic character for this aromatic molecule. Extended Townes-Dailey analyses were used to determine the B and N electron sp(2) hybridized and p-orbital occupations. These results are compared with electron orbital occupations from the natural bond orbital option in theoretical calculations. From the analyses, it was determined that BN-naphthalene has aromatic character similar to that of other N-containing aromatics. The results are compared with similar results for B-N bonding in 1,2-dihydro-1,2-azaborine and BN-cyclohexene. Accurate and precise structural parameters were obtained from the microwave measurements on seven isotopologues and from high-level G09 calculations. PMID- 27004874 TI - VUV and soft x-ray ionization of a plant volatile: Vanillin (C8H8O3). AB - Plant volatiles are emitted by plants in response to several forms of stress, including interaction with energetic photons. In the present work, we discuss the interaction of extreme UV and soft X-ray photons with a plant volatile, vanillin. The single and double (multiple) ionization of the vanillin molecule have been studied for the first time using time-of-flight mass spectrometry and VUV and soft X-ray photons (synchrotron radiation, at 12.0 eV, 21.2 eV, 130 eV, 310 eV, 531 eV, and 550 eV). At 12.0 and 21.2 eV, only singly charged species are observed and the parent ion, C8H8O3 (+), is the dominant species. Energy differences for some selected fragments were calculated theoretically in this energy region. At 130 eV, direct double and triple ionization of the valence electrons may occur. The fragmentation increases and CHO(+) becomes one of the main cations in the mass spectrum. The molecular ion is still the dominant species, but other fragments, such as C6H5O(+), begin to present similar intensities. At 310 eV, C 1s electrons may be ionized and Auger processes give rise to dissociative doubly ionized cations. Ionization around the O 1s edge has been studied both at the 531 eV resonance and above the ionization edge. Resonant and normal Auger processes play a significant role in each case and a large fragmentation of the molecule is observed at both photon energies, with intense fragments such as CHO(+) and CH3 (+) being clearly observed. A near edge X-ray absorption fine structure spectrum of the vanillin molecule was obtained around the O 1s ionization threshold. In addition, the fragmentation of vanillin has also been studied using a fast beam of electrons (800 eV), for the sake of comparison. PMID- 27004875 TI - Origin of selenium-gold interaction in F2CSe?AuY (Y = CN, F, Cl, Br, OH, and CH3): Synergistic effects. AB - Selenium-gold interaction plays an important role in crystal materials, molecular self-assembly, and pharmacochemistry involving gold. In this paper, we unveiled the mechanism and nature of selenium-gold interaction by studying complexes F2CSe?AuY (Y = CN, F, Cl, Br, OH, and CH3). The results showed that the formation of selenium-gold interaction is mainly attributed to the charge transfer from the lone pair of Se atom to the Au-Y anti-bonding orbital. Energy decomposition analysis indicated that the polarization energy is nearly equivalent to or exceeds the electrostatic term in the selenium-gold interaction. Interestingly, the chalcogen-gold interaction becomes stronger with the increase of chalcogen atomic mass in F2CX?AuCN (X = O, S, Se, and Te). The cyclic ternary complexes are formed with the introduction of NH3 into F2CSe?AuY, in which selenium-gold interaction is weakened and selenium-nitrogen interaction is strengthened due to the synergistic effects. PMID- 27004876 TI - The near-IR spectrum of NO(X(2)Pi)-Ne detected through excitation into the A state continuum: A joint experimental and theoretical study. AB - We present new measurements of the near IR spectrum of NO-Ne in the region of the first NO overtone transition. The IR absorption is detected by exciting the vibrationally excited complex to the A-state dissociation continuum. The resulting NO(A) fragment is subsequently ionized in the same laser pulse. Spectra of the two lowest bands, A and B, are recorded. The spectra are compared with calculated spectra based on bound states derived from a new set of high level ab initio potential energy surfaces (PESs). For the calculation, the PESs are used with either fixed NO intermolecular distance or averaged for the vibrational states of NO (X, v = 0 or 2). Spectra based on the new PESs reproduce the experimental spectra better than theoretical spectra based on the older PESs of M. H. Alexander et al. [J. Chem. Phys. 114, 5588 (2001)]. Especially, spectra based on the two different vibrationally averaged PESs show a marked improvement in comparison to the one based on the fixed internuclear NO-distance. A fitted set of spectroscopic constants allows to reproduce most of the finer details of the measured spectra. Monitoring simultaneously the NO fragment ion and the parent ion channels while scanning the UV wavelength through the NO A-X hot-band region enabled us to confirm the NO-Ne A-state dissociation limit of 44233 +/- 5 cm(-1). These measurements also confirm the absence of a structured NO-Ne spectrum involving the A-state. PMID- 27004877 TI - Reexamining the high-order harmonic generation of HD molecule in non-Born Oppenheimer approximation. AB - The high-order harmonic generation of the HD molecule is studied in non-Born Oppenheimer approximation. It is found that there are only the odd harmonics in the harmonic spectrum of the HD molecule though the generation of even harmonics is possible in principle. Theoretical analysis [T. Kreibich et al., Phys. Rev. Lett. 87, 103901 (2001)] reveals that the nuclear dipole moment can contribute to the generation of the even harmonics, but the acceleration of the nucleus is about three orders of magnitude less than that of the electron. Hence, the even harmonics cannot be observed in the harmonic spectrum of the HD molecule. PMID- 27004878 TI - The closo-Si12C12 molecule from cluster to crystal: A theoretical prediction. AB - The structure of closo-Si12C12 is unique among stable SinCm isomers (n, m > 4) because of its high symmetry, pi-pi stacking of C6 rings and unsaturated silicon atoms at symmetrical peripheral positions. Dimerization potential surfaces reveal various dimerization reactions that form between two closo-Si12C12 molecules through Si-Si bonds at unsaturated Si atoms. As a result the closo-Si12C12 molecule is capable of polymerization to form stable 1D polymer chains, 2D crystal layers, and 3D crystals. 2D crystal structures formed by side-side polymerization satisfy eight Si valences on each monomer without large distortion of the monomer structure. 3D crystals are formed by stacking 2D structures in the Z direction, preserving registry of C6 rings in monomer moiety. PMID- 27004879 TI - Single-molecule electronics: Cooling individual vibrational modes by the tunneling current. AB - Electronic devices composed of single molecules constitute the ultimate limit in the continued downscaling of electronic components. A key challenge for single molecule electronics is to control the temperature of these junctions. Controlling heating and cooling effects in individual vibrational modes can, in principle, be utilized to increase stability of single-molecule junctions under bias, to pump energy into particular vibrational modes to perform current-induced reactions, or to increase the resolution in inelastic electron tunneling spectroscopy by controlling the life-times of phonons in a molecule by suppressing absorption and external dissipation processes. Under bias the current and the molecule exchange energy, which typically results in heating of the molecule. However, the opposite process is also possible, where energy is extracted from the molecule by the tunneling current. Designing a molecular "heat sink" where a particular vibrational mode funnels heat out of the molecule and into the leads would be very desirable. It is even possible to imagine how the vibrational energy of the other vibrational modes could be funneled into the "cooling mode," given the right molecular design. Previous efforts to understand heating and cooling mechanisms in single molecule junctions have primarily been concerned with small models, where it is unclear which molecular systems they correspond to. In this paper, our focus is on suppressing heating and obtaining current-induced cooling in certain vibrational modes. Strategies for cooling vibrational modes in single-molecule junctions are presented, together with atomistic calculations based on those strategies. Cooling and reduced heating are observed for two different cooling schemes in calculations of atomistic single molecule junctions. PMID- 27004880 TI - Five ab initio potential energy and dipole moment surfaces for hydrated NaCl and NaF. I. Two-body interactions. AB - We report full-dimensional, ab initio-based potentials and dipole moment surfaces for NaCl, NaF, Na(+)H2O, F(-)H2O, and Cl(-)H2O. The NaCl and NaF potentials are diabatic ones that dissociate to ions. These are obtained using spline fits to CCSD(T)/aug-cc-pV5Z energies. In addition, non-linear least square fits using the Born-Mayer-Huggins potential are presented, providing accurate parameters based strictly on the current ab initio energies. The long-range behavior of the NaCl and NaF potentials is shown to go, as expected, accurately to the point-charge Coulomb interaction. The three ion-H2O potentials are permutationally invariant fits to roughly 20,000 coupled cluster CCSD(T) energies (awCVTZ basis for Na(+) and aVTZ basis for Cl(-) and F(-)), over a large range of distances and H2O intramolecular configurations. These potentials are switched accurately in the long range to the analytical ion-dipole interactions, to improve computational efficiency. Dipole moment surfaces are fits to MP2 data; for the ion-ion cases, these are well described in the intermediate- and long-range by the simple point charge expression. The performance of these new fits is examined by direct comparison to additional ab initio energies and dipole moments along various cuts. Equilibrium structures, harmonic frequencies, and electronic dissociation energies are also reported and compared to direct ab initio results. These indicate the high fidelity of the new PESs. PMID- 27004881 TI - Non-linear dielectric signatures of entropy changes in liquids subject to time dependent electric fields. AB - A model of non-linear dielectric polarization is studied in which the field induced entropy change is the source of polarization dependent retardation time constants. Numerical solutions for the susceptibilities of the system are obtained for parameters that represent the dynamic and thermodynamic behavior of glycerol. The calculations for high amplitude sinusoidal fields show a significant enhancement of the steady state loss for frequencies below that of the low field loss peak. Also at relatively low frequencies, the third harmonic susceptibility spectrum shows a "hump," i.e., a maximum, with an amplitude that increases with decreasing temperature. Both of these non-linear effects are consistent with experimental evidence. While such features have been used to conclude on a temperature dependent number of dynamically correlated particles, Ncorr, the present result demonstrates that the third harmonic susceptibility display a peak with an amplitude that tracks the variation of the activation energy in a model that does not involve dynamical correlations or spatial scales. PMID- 27004882 TI - A spherical cavity model for quadrupolar dielectrics. AB - The dielectric properties of a fluid composed of molecules possessing both dipole and quadrupole moments are studied based on a model of the Onsager type (molecule in the centre of a spherical cavity). The dielectric permittivity epsilon and the macroscopic quadrupole polarizability alphaQ of the fluid are related to the basic molecular characteristics (molecular dipole, polarizability, quadrupole, quadrupolarizability). The effect of alphaQ is to increase the reaction field, to bring forth reaction field gradient, to decrease the cavity field, and to bring forth cavity field gradient. The effects from the quadrupole terms are significant in the case of small cavity size in a non-polar liquid. The quadrupoles in the medium are shown to have a small but measurable effect on the dielectric permittivity of several liquids (Ar, Kr, Xe, CH4, N2, CO2, CS2, C6H6, H2O, CH3OH). The theory is used to calculate the macroscopic quadrupolarizabilities of these fluids as functions of pressure and temperature. The cavity radii are also determined for these liquids, and it is shown that they are functions of density only. This extension of Onsager's theory will be important for non-polar solutions (fuel, crude oil, liquid CO2), especially at increased pressures. PMID- 27004883 TI - A critical appraisal of the zero-multipole method: Structural, thermodynamic, dielectric, and dynamical properties of a water system. AB - We performed extensive and strict tests for the reliability of the zero-multipole (summation) method (ZMM), which is a method for estimating the electrostatic interactions among charged particles in a classical physical system, by investigating a set of various physical quantities. This set covers a broad range of water properties, including the thermodynamic properties (pressure, excess chemical potential, constant volume/pressure heat capacity, isothermal compressibility, and thermal expansion coefficient), dielectric properties (dielectric constant and Kirkwood-G factor), dynamical properties (diffusion constant and viscosity), and the structural property (radial distribution function). We selected a bulk water system, the most important solvent, and applied the widely used TIP3P model to this test. In result, the ZMM works well for almost all cases, compared with the smooth particle mesh Ewald (SPME) method that was carefully optimized. In particular, at cut-off radius of 1.2 nm, the recommended choices of ZMM parameters for the TIP3P system are alpha <= 1 nm(-1) for the splitting parameter and l = 2 or l = 3 for the order of the multipole moment. We discussed the origin of the deviations of the ZMM and found that they are intimately related to the deviations of the equilibrated densities between the ZMM and SPME, while the magnitude of the density deviations is very small. PMID- 27004884 TI - A polarizable QM/MM approach to the molecular dynamics of amide groups solvated in water. AB - The infrared (IR) spectra of polypeptides are dominated by the so-called amide bands. Because they originate from the strongly polar and polarizable amide groups (AGs) making up the backbone, their spectral positions sensitively depend on the local electric fields. Aiming at accurate computations of these IR spectra by molecular dynamics (MD) simulations, which derive atomic forces from a hybrid quantum and molecular mechanics (QM/MM) Hamiltonian, here we consider the effects of solvation in bulk liquid water on the amide bands of the AG model compound N methyl-acetamide (NMA). As QM approach to NMA we choose grid-based density functional theory (DFT). For the surrounding MM water, we develop, largely based on computations, a polarizable molecular mechanics (PMM) model potential called GP6P, which features six Gaussian electrostatic sources (one induced dipole, five static partial charge distributions) and, therefore, avoids spurious distortions of the DFT electron density in hybrid DFT/PMM simulations. Bulk liquid GP6P is shown to have favorable properties at the thermodynamic conditions of the parameterization and beyond. Lennard-Jones (LJ) parameters of the DFT fragment NMA are optimized by comparing radial distribution functions in the surrounding GP6P liquid with reference data obtained from a "first-principles" DFT-MD simulation. Finally, IR spectra of NMA in GP6P water are calculated from extended DFT/PMM-MD trajectories, in which the NMA is treated by three different DFT functionals (BP, BLYP, B3LYP). Method-specific frequency scaling factors are derived from DFT-MD simulations of isolated NMA. The DFT/PMM-MD simulations with GP6P and with the optimized LJ parameters then excellently predict the effects of aqueous solvation and deuteration observed in the IR spectra of NMA. As a result, the methods required to accurately compute such spectra by DFT/PMM-MD also for larger peptides in aqueous solution are now at hand. PMID- 27004885 TI - Effect of water on structure and dynamics of [BMIM][PF6] ionic liquid: An all atom molecular dynamics simulation investigation. AB - Composition dependent structural and dynamical properties of aqueous hydrophobic 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) ionic liquid (IL) have been investigated by using all-atom molecular dynamics simulation. We observe that addition of water does not increase significant number of dissociated ions in the solution over the pure state. As a consequence, self diffusion coefficient of the cation and anion is comparable to each other at all water concentration similar to that is observed for the pure state. Voronoi polyhedra analysis exhibits strong dependence on the local environment of IL concentration. Void and neck distributions in Voronoi tessellation are approximately Gaussian for pure IL but upon subsequent addition of water, we observe deviation from the Gaussian behaviour with an asymmetric broadening with long tail of exponential decay at large void radius, particularly at higher water concentrations. The increase in void space and neck size at higher water concentration facilitates ionic motion, thus, decreasing dynamical heterogeneity and IL reorientation time and increases self-diffusion coefficient significantly. PMID- 27004886 TI - Nonlinear dielectric spectroscopy in a fragile plastic crystal. AB - In this work we provide a thorough examination of the nonlinear dielectric properties of a succinonitrile-glutaronitrile mixture, representing one of the rare examples of a plastic crystal with fragile glassy dynamics. The detected alteration of the complex dielectric permittivity under high fields can be explained considering the heterogeneous nature of glassy dynamics and a field induced variation of entropy. While the first mechanism was also found in structural glass formers, the latter effect seems to be more pronounced in plastic crystals. Moreover, the third harmonic component of the dielectric susceptibility is reported, revealing a hump-like spectral shape as predicted, e.g., within a model considering cooperative molecular dynamics. If assuming the validity of this model, one can deduce the temperature dependence of the number of correlated molecules Ncorr from these data. In accord with the fragile nature of the glass transition in this plastic crystal, we obtain a relatively strong temperature dependence of Ncorr, in contrast to the much weaker temperature dependence in plastic-crystalline cyclo-octanol, whose glass transition is of strong nature. PMID- 27004887 TI - Effect of the electrostatic surface potential on the oligomerization of full length human recombinant prion protein at single-molecule level. AB - The electrostatic surface potential (ESP) of prion oligomers has critical influences on the aggregating processes of the prion molecules. The atomic force microscopy (AFM) and structural simulation were combined to investigate the molecular basis of the full-length human recombinant prion oligomerization on mica surfaces. The high resolution non-intrusive AFM images showed that the prion oligomers formed different patterns on mica surfaces at different buffer pH values. The basic binding units for the large oligomers were determined to be prion momoners (Ms), dimers (Ds), and trimers (Ts). The forming of the D and T units happened through the binding of hydrophobic beta-sheets of the M units. In contrast, the alpha-helices of these M, D, and T units were the binding areas for the formation of large oligomers. At pH 4.5, the binding units M, D, and T showed clear polarized ESP distributions on the surface domains, while at pH 7.0, they showed more evenly distributed ESPs. Based on the conformations of oligomers observed from AFM images, the D and T units were more abundantly on mica surface at pH 4.5 because the ESP re-distribution of M units helped to stabilize these larger oligomers. The amino acid side chains involved in the binding interfaces were stabilized by hydrogen bonds and electrostatic interactions. The detailed analysis of the charged side chains at pH 4.5 indicated that the polarized ESPs induced the aggregations among M, D, and T to form larger oligomers. Therefore, the hydrogen bonds and electrostatic interactions worked together to form the stabilized prion oligomers. PMID- 27004888 TI - Surface structure of imidazolium-based ionic liquids: Quantitative comparison between simulations and high-resolution RBS measurements. AB - Elemental depth profiles of 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([CnMIM][TFSI], n = 4, 6, 8) are measured using high-resolution Rutherford backscattering spectroscopy (HRBS). The profiles are compared with the results of molecular dynamics (MD) simulations. Both MD simulations and HRBS measurements show that the depth profiles deviate from the uniform stoichiometric composition in the surface region, showing preferential orientations of ions at the surface. The MD simulations qualitatively reproduce the observed HRBS profiles but the agreement is not satisfactory. The observed discrepancy is ascribed to the capillary waves. By taking account of the surface roughness induced by the capillary waves, the agreement becomes almost perfect. PMID- 27004889 TI - Atomically resolved structure of ligand-protected Au9 clusters on TiO2 nanosheets using aberration-corrected STEM. AB - Triphenylphosphine ligand-protected Au9 clusters deposited onto titania nanosheets show three different atomic configurations as observed by scanning transmission electron microscopy. The configurations observed are a 3-dimensional structure, corresponding to the previously proposed Au9 core of the clusters, and two pseudo-2-dimensional (pseudo-2D) structures, newly found by this work. With the help of density functional theory (DFT) calculations, the observed pseudo-2D structures are attributed to the low energy, de-ligated structures formed through interaction with the substrate. The combination of scanning transmission electron microscopy with DFT calculations thus allows identifying whether or not the deposited Au9 clusters have been de-ligated in the deposition process. PMID- 27004890 TI - Tuning the band gap of silicene by functionalisation with naphthyl and anthracyl groups. AB - Silicene is a relatively new material consisting of a two-dimensional sheet of silicon atoms. Functionalisation of silicene with different chemical groups has been suggested as a way to tune its electronic properties. In this work, density functional theory calculations and ab initio molecular dynamics simulations are used to examine the effects of functionalisation with naphthyl or anthracyl groups, which are two examples of small polycyclic aromatic hydrocarbons (PAHs). Different attachment positions on the naphthyl and anthracyl groups were compared, as well as different thicknesses of the silicene nanosheet. It was found that the carbon attachment position farthest from the bond fusing the aromatic rings gave the more stable structures for both functional groups. All structures showed direct band gaps, with tuning of the band gap being achievable by increasing the length of the PAH or the thickness of the silicene. Hence, modifying the functional group or thickness of the silicene can both be used to alter the electronic properties of silicene making it a highly promising material for use in future electronic devices and sensors. PMID- 27004891 TI - Determination of the solid surface critical exponent beta1 from contact-angle variation on approach to a wetting transition: Cyclohexane/aniline/quartz. AB - The three-phase contact angle (theta) for the system cyclohexane/aniline/quartz has been measured from drop shapes as a function of temperature on approach to the cyclohexane/aniline upper consolute solution temperature Tc. The experiments employed exacting criteria previously established for thermodynamic-quality measurements at fluid interfaces. A first-order wetting transition from partial wetting to complete wetting was observed at a temperature Tw, 2.12 K below Tc. The contact angle vanishes at Tw, scaling as cos theta ~ |T - Tc|(beta1-MU) for T < Tw and cos theta = 1.0 for Tw < T < Tc. The experimental results give a value for beta1 = 0.74 +/- 0.03, in agreement with theoretical calculations. The data clearly rule out higher order contributions to the change in the contact angle near the critical point for this system. These results are in marked contrast to previous measurements on this system from measurements of capillary rise and meniscus curvature. PMID- 27004892 TI - Spin orientations of the spin-half Ir(4+) ions in Sr3NiIrO6, Sr2IrO4, and Na2IrO3: Density functional, perturbation theory, and Madelung potential analyses. AB - The spins of the low-spin Ir(4+) (S = 1/2, d(5)) ions at the octahedral sites of the oxides Sr3NiIrO6, Sr2IrO4, and Na2IrO3 exhibit preferred orientations with respect to their IrO6 octahedra. We evaluated the magnetic anisotropies of these S = 1/2 ions on the basis of density functional theory (DFT) calculations including spin-orbit coupling (SOC), and probed their origin by performing perturbation theory analyses with SOC as perturbation within the LS coupling scheme. The observed spin orientations of Sr3NiIrO6 and Sr2IrO4 are correctly predicted by DFT calculations, and are accounted for by the perturbation theory analysis. As for the spin orientation of Na2IrO3, both experimental studies and DFT calculations have not been unequivocal. Our analysis reveals that the Ir(4+) spin orientation of Na2IrO3 should have nonzero components along the c- and a axis directions. The spin orientations determined by DFT calculations are sensitive to the accuracy of the crystal structures employed, which is explained by perturbation theory analyses when interactions between adjacent Ir(4+) ions are taken into consideration. There are indications implying that the 5d electrons of Na2IrO3 are less strongly localized compared with those of Sr3NiIrO6 and Sr2IrO4. This implication was confirmed by showing that the Madelung potentials of the Ir(4+) ions are less negative in Na2IrO3 than in Sr3NiIrO6 and Sr2IrO4. Most transition-metal S = 1/2 ions do have magnetic anisotropies because the SOC induces interactions among their crystal-field split d-states, and the associated mixing of the states modifies only the orbital parts of the states. This finding cannot be mimicked by a spin Hamiltonian because this model Hamiltonian lacks the orbital degree of freedom, thereby leading to the spin-half syndrome. The spin-orbital entanglement for the 5d spin-half ions Ir(4+) is not as strong as has been assumed. PMID- 27004893 TI - Mathematical model for self-propelled droplets driven by interfacial tension. AB - We propose a model for the spontaneous motion of a droplet induced by inhomogeneity in interfacial tension. The model is derived from a variation of the Lagrangian of the system and we use a time-discretized Morse flow scheme to perform its numerical simulations. Our model can naturally simulate the dynamics of a single droplet, as well as that of multiple droplets, where the volume of each droplet is conserved. We reproduced the ballistic motion and fission of a droplet, and the collision of two droplets was also examined numerically. PMID- 27004894 TI - Structural anisotropy results in strain-tunable electronic and optical properties in monolayer GeX and SnX (X = S, Se, Te). AB - Using first-principles calculations, the structural and electronic properties of group-IV monochalcogenide monolayers are investigated. It is demonstrated that all the monolayers employed here possess moderate indirect bandgaps. In-plane elastic stiffness calculation demonstrates the structural anisotropy in these materials, further resulting in anisotropic response to in-plane strains in their electronic properties and anisotropic optical properties. The bandgaps of GeX and SnX monolayers can be linearly reduced by applied in-plane compressive strains and the semiconductor-to-metal transition can be realized under large compressive strains; while tensile strains exert less influence on the electronic properties in comparison to compressive strains. Some monolayers will experience indirect-to direct bandgap transition when subjected to proper strains. A further insight into the variation of bandgaps of these monolayers can be obtained from the changing band edges. PMID- 27004895 TI - Understanding the ordering mechanisms of self-assembled nanostructures of block copolymers during zone annealing. AB - A theoretical method based on dynamic version of self-consistent field theory is extended to investigate directed self-assembly behaviors of block copolymers subjected to zone annealing. The ordering mechanisms and orientation modulation of microphase-separated nanostructures of block copolymers are discussed in terms of sweep velocity, wall preference, and Flory-Huggins interaction parameter. The simulated results demonstrate that the long-range ordered nanopatterns are achieved by lowering the sweep velocity of zone annealing due to the incorporation of templated ordering of block copolymers. The surface enrichment by one of the two polymer species induces the orientation modulation of defect free nanostructures through finely tuning the composition of block copolymers and the preference of walls. Additionally, the Flory-Huggins interaction parameters of block copolymers in the distinct regions are main factors to design the zone annealing process for creating the highly ordered nanostructures with single orientation. PMID- 27004896 TI - Spectroscopic studies of the mechanism of reversible photodegradation of 1 substituted aminoanthraquinone-doped polymers. AB - The mechanism of reversible photodegradation of 1-substituted aminoanthraquinones doped into poly(methyl methacrylate) and polystyrene is investigated. Time dependent density functional theory is employed to predict the transition energies and corresponding oscillator strengths of the proposed reversibly and irreversibly damaged dye species. Ultraviolet-visible and Fourier transform infrared (FTIR) spectroscopy are used to characterize which species are present. FTIR spectroscopy indicates that both dye and polymer undergo reversible photodegradation when irradiated with a visible laser. These findings suggest that photodegradation of 1-substituted aminoanthraquinones doped in polymers originates from interactions between dyes and photoinduced thermally degraded polymers, and the metastable product may recover or further degrade irreversibly. PMID- 27004897 TI - Influence of network topology on the swelling of polyelectrolyte nanogels. AB - It is well-known that the swelling behavior of ionic nanogels depends on their cross-link density; however, it is unclear how different topologies should affect the response of the polyelectrolyte network. Here we perform Monte Carlo simulations to obtain the equilibrium properties of ionic nanogels as a function of salt concentration Cs and the fraction f of ionizable groups in a polyelectrolyte network formed by cross-links of functionality z. Our results indicate that the network with cross-links of low connectivity result in nanogel particles with higher swelling ratios. We also confirm a de-swelling effect of salt on nanogel particles. PMID- 27004898 TI - The thermodynamics and kinetics of a nucleotide base pair. AB - The thermodynamic and kinetic parameters of an RNA base pair were obtained through a long-time molecular dynamics simulation of the opening-closing switch process of the base pair near its melting temperature. The thermodynamic parameters were in good agreement with the nearest-neighbor model. The opening rates showed strong temperature dependence, however, the closing rates showed only weak temperature dependence. The transition path time was weakly temperature dependent and was insensitive to the energy barrier. The diffusion constant exhibited super-Arrhenius behavior. The free energy barrier of breaking a single base stack results from the enthalpy increase, DeltaH, caused by the disruption of hydrogen bonding and base-stacking interactions. The free energy barrier of base pair closing comes from the unfavorable entropy loss, DeltaS, caused by the restriction of torsional angles. These results suggest that a one-dimensional free energy surface is sufficient to accurately describe the dynamics of base pair opening and closing, and the dynamics are Brownian. PMID- 27004899 TI - Erratum: "Accurate intermolecular ground-state potential-energy surfaces of the HCCH-He, Ne, and Ar van der Waals complexes" [J. Chem. Phys. 123, 014309 (2005)]. PMID- 27004900 TI - Attitudes towards second opinion services in cancer care: a nationwide survey of oncologists in Korea. AB - OBJECTIVE: Second opinion is a common phenomenon in many health systems, especially in the care of patients with cancer. However, it is not clear whether second opinion seeking should be promoted or discouraged and how second opinion services and policies can be better formalized to maximize the benefits and minimize the disadvantages. METHODS: A nationwide survey was conducted with a representative sample of 678 physicians involved in cancer care (75.5% participation rate) recruited in 13 cancer centres. RESULTS: Most physicians involved with cancer care perceived patients' second opinion seeking as a legitimate right (96.0%) and they acknowledged the need for second opinion services under certain conditions (98.2%). Many believed that second opinions can enhance patient satisfaction (77.3%) and quality of care (74.3%), but they also had concerns about increase in healthcare and societal costs (91.3%) and concentration in a high-volume centre (90.7%). While the majority agreed with the involvement of the first opinion physicians in the second opinion services (69.5%), there were mixed opinions regarding the desirability of remote (teleconsultation) second opinion services (49.0%) and coverage by national health insurance (51.9%). CONCLUSION: Physicians were generally positive to second opinion services and expected positive consequences in terms of patient satisfaction and quality of care. However, they had concerns about the consequences regarding cost and equity, and disagreements were observed regarding the way to improve second opinion services. The physicians' opinions revealed in our study will be helpful in developing clearer guidelines used to maximize the benefits of second opinion services. PMID- 27004901 TI - Type distribution of myeloid leukemia from Cancer Incidence in Five Continents Vol. X. PMID- 27004902 TI - Endobronchial ultrasound-guided transbronchial needle aspiration of hilar and mediastinal lymph nodes detected on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. AB - OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration is of diagnostic value in hilar/mediastinal (N1/N2) lymph node staging. We assessed the utility of endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients with N1/N2 lymph nodes detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. METHODS: Fifty lung cancer patients with N1/N2 disease on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography underwent endobronchial ultrasound-guided transbronchial needle aspiration for pathological lymph nodes between November 2012 and April 2015. The diagnostic performance of endobronchial ultrasound guided transbronchial needle aspiration, lymph node site and size, number of needle passes and complications were evaluated retrospectively from patients' medical records. Malignancy was defined as a maximum standardized uptake value (SUVmax) >2.5. RESULTS: The median longest diameter of the 61 lymph nodes (29 subcarinal, 21 right lower paratracheal, 6 left lower paratracheal, 4 right hilar and 1 upper paratracheal) was 23.4 mm (range: 10.4-45.7); the median number of needle passes was 2 (range: 1-5). There were no severe complications. A definitive diagnosis was made by endobronchial ultrasound-guided transbronchial needle aspiration in 39 patients (31 adenocarcinomas, 3 small-cell carcinomas, 2 squamous-cell carcinomas, 3 large-cell neuroendocrine carcinomas). In the remaining 11 patients, the diagnosis was indefinite: insufficient endobronchial ultrasound-guided transbronchial needle aspiration material was collected in two patients and non-specific lymphadenopathy was confirmed by endobronchial ultrasound-guided transbronchial needle aspiration or thoracotomy in the other nine patients. The mean lymph node SUVmax was 7.09 (range: 2.90-26.9) and was significantly higher in true-positive than in false-positive nodes (P < 0.05, t test). Non-specific lymphadenopathy was diagnosed by expert visual interpretation of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography images in five of the nine patients. CONCLUSION: Endobronchial ultrasound-guided transbronchial needle aspiration accurately diagnoses N1/N2 disease detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography. PMID- 27004903 TI - An epidermal growth factor receptor exon 19 mutation in a mucin-producing gastric cancer sample from a Chinese patient. AB - OBJECTIVE: To determine whether a subgroup of gastric cancer patients might benefit from epidermal growth factor receptor-tyrosine kinase inhibitors. METHODS: A total of 103 gastric cancer samples were collected for this study. High-resolution melting and deoxyribonucleic acid sequencing were used to detect epidermal growth factor receptor mutations in exons 19 and 21. RESULTS: Polymerase chain reaction-high-resolution melting was successfully performed on all 103 samples. Aberrant melting curves were found in only one sample. Sanger sequencing revealed a 15 bp deletion (c.2235_2249del; p.Glu746_Ala750del) in epidermal growth factor receptor exon 19. The sample was from a male patient, and the pathological diagnosis was a mucin-producing gastric cancer with lymph node metastasis. To date, this is the first report on epidermal growth factor receptor exon 19 mutation in gastric cancer. CONCLUSIONS: An epidermal growth factor receptor mutation in exon 19 was identified in mucin-producing gastric cancer sample from a male patient. This mutation indicates that the small subgroup of patients with mucin-producing gastric cancer might benefit from epidermal growth factor receptor-tyrosine kinase inhibitors. PMID- 27004904 TI - MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. AB - We present the latest version of the Molecular Evolutionary Genetics Analysis (Mega) software, which contains many sophisticated methods and tools for phylogenomics and phylomedicine. In this major upgrade, Mega has been optimized for use on 64-bit computing systems for analyzing larger datasets. Researchers can now explore and analyze tens of thousands of sequences in Mega The new version also provides an advanced wizard for building timetrees and includes a new functionality to automatically predict gene duplication events in gene family trees. The 64-bit Mega is made available in two interfaces: graphical and command line. The graphical user interface (GUI) is a native Microsoft Windows application that can also be used on Mac OS X. The command line Mega is available as native applications for Windows, Linux, and Mac OS X. They are intended for use in high-throughput and scripted analysis. Both versions are available from www.megasoftware.net free of charge. PMID- 27004905 TI - Development and initial testing of a tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses (TTIP-PRO). AB - Individuals with opioid use disorder experiencing a non-fatal opioid-overdose (OOD) are at heightened risk for future OODs; there are no interventions to facilitate treatment enrollment for these patients. Our goal was to develop and initially test the 'tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses' (TTIP-PRO), a computer-facilitated, peer-delivered, individually tailored secondary prevention intervention designed to: (i) encourage patients to initiate medication-assisted treatment (MAT) and (ii) increase OOD knowledge. A pre-post-study assessed TTIP-PRO-content acceptability and software performance. Two Peer Interventionists, who were abstinent from illicit opioids, enrolled in MAT and had experience with OOD, were recruited from a MAT clinic. Recruitment letters were sent to patients treated for OOD in a hospital emergency department within the prior 8 months. Eight patients received TTIP-PRO and completed pre-/post-assessment. Peer Interventionists completed training within 4 h and reported high satisfaction with TTIP-PRO. There were no performance issues with the software. All participants rated TTIP-PRO as 'very helpful'. Participants' OOD knowledge increased significantly, with 69.9% correct responses pre-TTIP-PRO and 93.6% post-TTIP-PRO. Interest in receiving MAT, measured on a 10-point scale, increased from 8.1 to 9.5, but this change was not statistically significant. Further development and testing of TTIP-PRO appears warranted. PMID- 27004912 TI - The Greater Manchester experiment. PMID- 27004906 TI - Implemented or not implemented? Process evaluation of the school-based obesity prevention program DOiT and associations with program effectiveness. AB - This study investigates if and to what extent the Dutch Obesity Intervention in Teenagers (DOiT) program was implemented as intended and how this affected program effectiveness. We collected data at 20 prevocational education schools in the Netherlands. We assessed seven process indicators: recruitment, reach, dosage, fidelity, satisfaction, effectiveness and continuation. Data collection involved teacher questionnaires (n= 110), adolescent questionnaires and adiposity measures (n= 938). Using multi-level confirmatory factor analyses, we applied an innovative method to obtain explorative implementation index scores. The percentage of accomplished activities ranged from 9% (for 'closure meeting') up to 93% (for 'obtaining support within the school for adoption'). The percentage of lessons delivered decreased from 74 to 18% towards the end of the program. Fidelity to the teacher manual ranged from 85 to 26%. In general, teachers were satisfied with the DOiT lessons and teaching materials. Despite teachers' satisfaction with the DOiT lessons and teaching materials, degree of program implementation was lower than expected, especially towards the end of the program. Further, some evidence was found for an association between a higher implementation index score and program effectiveness, but more research is needed to test the validity of the implementation index. PMID- 27004913 TI - Circles of Support and personalization: Exploring the economic case. AB - Circles of Support aim to enable people with learning disabilities (and others) to live full lives as part of their communities. As part of a wider study of the economic case for community capacity building conducted from 2012 to 2014, we conducted a mixed methods study of five Circles in North West England. Members of these Circles were supporting adults with moderate to profound learning disabilities and provided accounts of success in enabling the core member to live more independent lives with improved social care outcomes within cost envelopes that appeared to be less than more traditional types of support. The Circles also reported success in harnessing community resources to promote social inclusion and improve well-being. This very small-scale study can only offer tentative evidence but does appear to justify more rigorous research into the potential of Circles to secure cost-effective means of providing support to people with learning disabilities than the alternative, which in most cases would have been a long-term residential care placement. PMID- 27004914 TI - First autopsy case report of Familial Mediterranean fever in a Japanese man. PMID- 27004916 TI - Using machine learning to assess covariate balance in matching studies. AB - In order to assess the effectiveness of matching approaches in observational studies, investigators typically present summary statistics for each observed pre intervention covariate, with the objective of showing that matching reduces the difference in means (or proportions) between groups to as close to zero as possible. In this paper, we introduce a new approach to distinguish between study groups based on their distributions of the covariates using a machine-learning algorithm called optimal discriminant analysis (ODA). Assessing covariate balance using ODA as compared with the conventional method has several key advantages: the ability to ascertain how individuals self-select based on optimal (maximum accuracy) cut-points on the covariates; the application to any variable metric and number of groups; its insensitivity to skewed data or outliers; and the use of accuracy measures that can be widely applied to all analyses. Moreover, ODA accepts analytic weights, thereby extending the assessment of covariate balance to any study design where weights are used for covariate adjustment. By comparing the two approaches using empirical data, we are able to demonstrate that using measures of classification accuracy as balance diagnostics produces highly consistent results to those obtained via the conventional approach (in our matched-pairs example, ODA revealed a weak statistically significant relationship not detected by the conventional approach). Thus, investigators should consider ODA as a robust complement, or perhaps alternative, to the conventional approach for assessing covariate balance in matching studies. PMID- 27004915 TI - Simultaneous tracking of drug molecules and carriers using aptamer-functionalized fluorescent superstable gold nanorod-carbon nanocapsules during thermo chemotherapy. AB - Controlling and monitoring the drug delivery process is critical to its intended therapeutic function. Many nanocarrier systems for drug delivery have been successfully developed. However, biocompatibility, stability, and simultaneously tracing drugs and nanocarriers present significant limitations. Herein, we have fabricated a multifunctional nanocomposite by coating the gold nanorod (AuNR) with a biocompatible, superstable and fluorescent carbon layer, obtaining the AuNR@carbon core-shell nanocapsule. In this system, the carbon shell, originally obtained in aqueous glucose solutions and, therefore, biocompatible in physiological environments, could be simply loaded with cell-specific aptamers and therapeutic molecules through pi-pi interactions, a useful tool for cancer targeted cellular imaging and therapy. Moreover, such a stable and intrinsic fluorescence effect of the AuNR@carbon enabled simultaneous tracking of released therapeutic molecules and nanocarriers under thermo-chemotherapy. The AuNR@carbons had high surface areas and stable shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications. PMID- 27004917 TI - Fibrinogen concentrate as a treatment for postpartum haemorrhage-induced coagulopathy: A study protocol for a randomised multicentre controlled trial. The fibrinogen in haemorrhage of DELivery (FIDEL) trial. AB - BACKGROUND: Postpartum haemorrhage (PPH) remains the leading cause for maternal mortality worldwide. Hypofibrinogenaemia has been identified as a major risk factor for progress towards severe PPH. The efficacy of fibrinogen concentrate supplementation in PPH has been shown in various clinical settings but the level of evidence is not sufficient to prove the benefit, evaluate the risks, and determine the value, timing and dose of fibrinogen supplementation in PPH. The FIDEL trial objective is to evaluate the impact of a therapeutic strategy based on the early administration of human fibrinogen concentrate compared to the current practice based on late administration in severe PPH patients requiring second line uterotonics. METHODS/DESIGN: This is a prospective multicentre, randomised, double-blind, placebo-controlled trial. A total of 412 patients will be randomised if they meet the following criteria: female patients>=18 years old, vaginal delivery, PPH requiring IV administration of prostaglandins (sulprostone) after 20 to 30minutes of oxytocin failure. The participants are assigned to receive either fibrinogen 3g or placebo infusions. The primary endpoint is a composite endpoint defined as the percentage of patients losing at least 4g/dL of Hb, and/or requiring a transfusion of at least 2 units of packed red blood cells, within the 48hours following fibrinogen administration. DISCUSSION: The purpose of this study is to demonstrate the efficacy and safety of an early fibrinogen concentrate infusion in uncontrolled active PPH. PMID- 27004918 TI - How patient families are provided with information during intensive care: A survey of practices. AB - BACKGROUND: Many critically ill patients are incapable of receiving information or expressing their own opinion on treatment decisions due to the severity of their disease, or because they are under sedation. French legislation requires that when a physician proposes further tests or treatment for a patient, this proposal should be accompanied by clear and honest information that is appropriate in view of the circumstances and the patient's state of health, and the physician must obtain the patient's consent before proceeding. However, this is often impossible in critical care. We evaluated whether provisions for surrogates are adequate in meeting information needs of patients and families in critical care. METHODS: Survey of intensive care physicians by electronic questionnaire in December 2010 and January 2011 to evaluate actual practices. The questionnaire comprised 6 domains covering various aspects relating to the information of patients' relatives as regards diagnostic testing in critical care, when the patient was unable to be appropriately informed. We recorded responders' socio-demographic data (age, how long in practice, where they practised). RESULTS: Among 1279 physicians contacted, 139 (10.8%) from 98 critical care departments (France, Belgium, Switzerland) responded. A total of 66.2% said they believed it is possible to perform diagnostic tests without informing the patient's relatives. Invasive or high-risk tests, time available to provide information, and quality of prior relations with the patient's family were factors likely to prompt the physician to inform the family, while potentially serious implications for the relatives, and degree of relation of the family member to the patient were reported to make the physician more reluctant to inform relatives. Less than 6% considered routine procedures to require provision of information to relatives. CONCLUSION: Our results suggest that modalities for providing information to families and relatives, as defined by current French legislation, are not suitable to the context of critical care. PMID- 27004919 TI - Male Presence can Increase Body Mass and Induce a Stress-Response in Female Mice Independent of Costs of Offspring Production. AB - Sexual reproduction in animals requires close interactions with the opposite sex. These interactions may generate costs of reproduction, because mates can induce detrimental physiological or physical effects on one another, due to their interest in maximising their own fitness. To understand how a male's presence influences aspects of female physiology implicated in reproductive costs in mice, independent of offspring production, we paired females with vasectomised, castrated or intact males, or other females. Being paired with a male, irrespective of his gonadal status, increased female weight. This effect was transient in females paired with castrated males but more persistent in those with vasectomised males. Those paired with males also showed an increase in corticosterone, suggesting an increased stress response. However, this was dependent on the gonadal status of the male housing partner, since those housed with vasectomised males had lower corticosterone than those with castrated males. Altered energy metabolism was only detectable in pregnant females, and oxidative stress was not consistently affected by a female's housing partner. These results suggest that a male's presence alters female weight, and stresses associated with reproduction could be induced by simply the presence of a male, but reduced by mating and/or being solicited to mate. PMID- 27004920 TI - Photoinduced valley-polarized current of layered MoS2 by electric tuning. AB - A photoinduced current of a layered MoS2-based transistor is studied from first principles. Under the illumination of circular polarized light, a valley polarized current is generated, which can be tuned by the gate voltage. For monolayer MoS2, the valley-polarized spin-up (down) electron current at K (K') points is induced by the right (left) circular polarized light. The valley polarization is found to reach +1.0 (-1.0) for the valley current that carried such a K (K') index. For bilayer MoS2, the spin-up (down) current can be induced at both K and K' valleys by the right (left) circular light. In contrast to monolayer MoS2, the photoinduced valley polarization shows asymmetric behavior upon reversal of the gate voltage. Our results show that the valley polarization of the photoinduced current can be modulated by the circular polarized light and the gate voltage. All the results can be well understood using a simple kp model. PMID- 27004921 TI - Adults are big children. PMID- 27004922 TI - Evaluation of resistance acquisition during tuberculosis treatment using whole genome sequencing. AB - Tuberculosis (TB) is still considered a major global public health problem in the world and there is a concern about the worldwide increase of drug-resistance (DR). This paper describes the analysis of three Mycobacterium tuberculosis isolates from a single patient collected over a long treatment period of time. DR was initially investigated through phenotypic testing, followed by line probe assays (LPAs) and whole genome sequencing (WGS). It presents an intriguing situation where a multidrug-resistant (MDR-) TB case was diagnosed and treated based only on late phenotypic drug susceptibility testing of isolate 1. During the treatment, another two isolates were cultivated: isolate 2, nine months after starting MDR-TB treatment; and isolate 3, cultivated five months later, during regular use of anti-TB drugs. These two isolates were evaluated using molecular LPA and WGS, retrospectively. All mutations detected by LPA were also detected in the WGS, including conversion from fluoroquinolones susceptibility to resistance from isolate 2 to isolate 3. WGS showed additional mutations, including some which may confer resistance to other drugs not tested (terizidone/cycloserine) and mutations with no correspondent resistance in drug susceptibility testing (streptomycin and second-line injectable drugs). PMID- 27004923 TI - A novel low-profile ventriculoamniotic shunt for foetal aqueductal stenosis. AB - This study proposed a novel ventriculoamniotic shunt device for foetal aqueductal stenosis treatment fabricated with 3Fr or 4Fr size catheters that have a longitudinal bending stiffness with kink resistance, sufficient luminal area for cerebrospinal fluid drainage and capacity for valve integration. Computational flow dynamics studies were carried out to optimise the device design, including size of the lumen and length of the device. An in vitro pressure and flow rate measurement test circuit was constructed to assess the high pressure relieving functionality of draining cerebrospinal fluid from foetal brain. Additionally, a resistance force measurement test platform was built to quantitatively evaluate the anchor performance of various geometric designs. The valve functionality was qualitatively evaluated through the visualisation of the flow patterns in the amniotic sac with injected red coloured fluid under stereomicroscopy. These in vitro results demonstrate the feasibility of the ventriculoamniotic shunt device designed for placement in the foetal brain. PMID- 27004924 TI - Assessment of inattention in the context of delirium screening: one size does not fit all! AB - BACKGROUND: Despite its high prevalence and deleterious consequences, delirium often goes undetected in older hospitalized patients and long-term care (LTC) residents. Inattention is a core symptom of this syndrome. The aim of this study was to explore the usefulness of ten simple and objective attention tests that would enable efficient delirium screening among this population. METHODS: This was a secondary analysis (n = 191) of a validation study conducted in one acute care hospital (ACH) and one LTC facility among older adults with, or without, cognitive impairment. The attention test tasks (n = 10) were drawn from the Concentration subscale the Hierarchic Dementia Scale (HDS). Delirium was defined as meeting the criteria for DSM-5 delirium. The Confusion Assessment Method (CAM) was used to determine the presence of delirium symptoms. RESULTS: The Months of the Year Backward (MOTYB) test, which 57% of participants completed successfully, showed the best balance between sensitivity and specificity (82.6%; 95% CI [61.2 95.0], and 62.5%; 95% CI [54.7-69.8] respectively) for the entire group. Subgroup analyses revealed that no test had both sensitivity and specificity over 50% in participants with cognitive impairment indicated in their medical chart. CONCLUSIONS: Our results revealed that these tests varied greatly in performance and none can be earmarked to become a single-item screening tool for delirium among older patients and residents with, or without, cognitive impairment. The presence of premorbid cognitive impairment may necessitate more extensive assessments of delirium, especially when a change in general status or mental state is observed. PMID- 27004925 TI - Assessment of Liliequist membrane by 3D-SPACE technique at 3 T. AB - INTRODUCTION: Liliequist membrane (LM) is the most important anatomic structure for the success of endoscopic third ventriculostomy (ETV). Identification of this membrane is difficult with conventional MRI techniques. The purpose of this retrospective study is to determine the impact of three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-SPACE) sequence with variant flip-angle mode (VFAM) in the assessment of LM at 3-T MRI devices. METHODS: 3D-SPACE with VFAM images were obtained in 445 patients. LM visibility and integrity were scored as 0 (good), 1 (moderate), and 2 (poor) on these images for each parts (sellar, diencephalic, and mesencephalic) and overall of the membrane. RESULTS: According to the LM overall integrity scores, 11 % (48 cases) of the patients had perforated membrane. According to subsegmental integrity scores, sellar part was completely intact in 63 % of patients, diencephalic segment was completely intact in 60 % of the patients, and mesencephalic segment was completely intact in 95 % of the patients. Visibility scores of the third ventricle inferior wall were significantly higher in the patients with intact LM (p = 0.001). There was not any statistically significant relationship between LM pattern and overall integrity (p = 0.352). LM attachment sites could be detected easier in the patients who had better visibility of third ventricle inferior wall or intact LM (p < 0.001 for both). CONCLUSION: 3D-SPACE technique is a useful alternative for the evaluation of morphology, integrity, individual variations, topographic relationships, and visibility of LM since it has some advantages including lower SAR values, fewer artifacts, and high-resolution images. PMID- 27004926 TI - Metal allergy in eyelid dermatitis and the evaluation of metal contents in eye shadows. AB - BACKGROUND: Allergic contact dermatitis is a common diagnosis in eyelid dermatitis. Sensitization to metals is prevalent in eyelid dermatitis and colour cosmetic products are frequently suspected as the source of metal exposure. OBJECTIVE: To investigate the contact allergens for eyelid dermatitis and to assess metal contents in eye shadow products. METHODS: Data were collected in the department of dermatology of Ewha Womans University hospital from December 1998 to February 2014. A total of 983 patients were patch tested during the period and 67 patients had eyelid dermatitis among them. To examine metal elements in colour cosmetic products for eyes, randomly selected 10 eye shadows were analysed. RESULTS: Frequent allergens were metals, thiomersal and phenylenediamine in patients with eyelid dermatitis. The sensitization rates of individual allergens were not significantly different between patients with eyelid dermatitis and without eyelid dermatitis. All 10 eye shadow products contained more than 5 ppm of at least one element, nickel, cobalt or chromium. CONCLUSION: Metals were top rank allergens in patients with eyelid dermatitis as in the remaining patients patch tested. The eye shadow products contained significant amount of nickel, cobalt or chromium to elicit allergic reactions. PMID- 27004927 TI - Evaluation of alternative sorbents for dispersive solid-phase extraction clean-up in the QuEChERS method for the determination of pesticide residues in rice by liquid chromatography with tandem mass spectrometry. AB - Many compounds are used for pest control during the production and storage of rice, making it necessary to employ multiclass methods for pesticide residues determination. For this purpose, QuEChERS-based methods are very efficient, fast and accurate, and improvements in the clean-up step are important, especially for complex matrices, like cereals. In this work, different sorbents such as chitosan, florisil((r)) , alumina, diatomaceous earth, graphitized carbon black, besides the commonly used primary secondary amine and octadecylsilane, were evaluated for dispersive solid-phase extraction clean-up in acetate-buffered QuEChERS method for the determination of residues of 20 representative pesticides and one metabolite in rice by liquid chromatography coupled to tandem mass spectrometry. The sorbent C18 presented the best results, however, chitosan showed similar results, and the best performance among the unconventional sorbents evaluated. The method limit of quantification, attending accuracy (70 120% recovery) and precision (RSD <=20%) criteria, ranged from 5 to 20 MUg/kg. Results showed that chitosan is an effective alternative to reduce analysis costs, maintaining the method reliability and accuracy. PMID- 27004928 TI - A Thermo- and Photo-Switchable Ruthenium Initiator For Olefin Metathesis. AB - A ruthenium carbene complex bearing azobenzene functionality is reported. The complex exists in the form of two isomers differing by the size of the chelate ring. Both isomers were isolated by applying kinetic or thermodynamic control during the synthesis and characterized by X-ray diffraction analysis. The isomerization of the complex was studied by UV/Vis spectroscopy. The stable isomer was tested as a catalyst in olefin metathesis. The complex was activated at about 100 degrees C to promote ring-closing and ring-opening polymerization metathesis reactions. The activation took place also at room temperature under middle ultraviolet radiation. PMID- 27004931 TI - Erratum: The evolution and population structure of Lactobacillus fermentum from different naturally fermented products as determined by multilocus sequence typing (MLST). PMID- 27004930 TI - Five Questions (with their Answers) on ER-Associated Degradation. AB - Production of a functional proteome is a major burden for our cells. Native proteins operate inside and outside the cells to eventually warrant life and adaptation to metabolic and environmental changes, there is no doubt that production and inappropriate handling of misfolded proteins may cause severe disease states. This review focuses on protein destruction, which is, paradoxically, a crucial event for cell and organism survival. It regulates the physiological turnover of proteins and the clearance of faulty biosynthetic products. It mainly relies on the intervention of two catabolic machineries, the ubiquitin proteasome system and the (auto)lysosomal system. Here, we have selected five questions dealing with how, why and when proteins produced in the mammalian endoplasmic reticulum are eventually selected for destruction. PMID- 27004932 TI - Three cases of anti-TNF induced myositis and literature review. AB - Anti-tumor necrosis factor (anti-TNF) drugs are frequently preferred in the treatment of rheumatologic diseases and other inflammatory diseases. The development of myositis after using anti-TNF is a rare clinical condition. Here we aimed to report cases who developed myositis after using anti-TNF and review the current literature. We report two cases of rheumatoid arthritis (RA) and a case of ankylosing spondylitis (AS) developed idiopathic inflammatory myopathy following anti-TNF therapy. In conclusion, myositis could develop during anti-TNF therapy, so these patients should be evaluated carefully initially for myositis and should be closely monitored due to the potential for developing myositis in treatment process. PMID- 27004933 TI - Sex-specific neural circuits of emotion regulation in the centromedial amygdala. AB - Sex-related differences in emotion regulation (ER) in the frequency power distribution within the human amygdala, a brain region involved in emotion processing, have been reported. However, how sex differences in ER are manifested in the brain networks which are seeded on the amygdala subregions is unclear. The goal of this study was to investigate this issue from a brain network perspective. Utilizing resting-state functional connectivity (RSFC) analysis, we found that the sex-specific functional connectivity patterns associated with ER trait level were only seeded in the centromedial amygdala (CM). Women with a higher trait-level ER had a stronger negative RSFC between the right CM and the medial superior frontal gyrus (mSFG), and stronger positive RSFC between the right CM and the anterior insula (AI) and the superior temporal gyrus (STG). But men with a higher trait-level ER was associated with weaker negative RSFC of the right CM-mSFG and positive RSFCs of the right CM-left AI, right CM-right AI/STG, and right CM-left STG. These results provide evidence for the sex-related effects in ER based on CM and indicate that men and women may differ in the neural circuits associated with emotion representation and integration. PMID- 27004934 TI - An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression. AB - Previous studies have shown promising results when using an agonistic anti-4-1BB antibody treatment against established tumors. While this is promising, this type of treatment can induce severe side effects. Therefore, we decided to incorporate the membrane form of 4-1BB ligand (4-1BBL) in a replicative deficient adenovirus vaccine expressing the invariant chain (Ii) adjuvant fused to a tumor associated antigen (TAA). The Ii adjuvant increases and prolongs TAA specific CD8+ T cells as previously shown and local expression of 4-1BBL was chosen to avoid the toxicity associated with systemic antibody administration. Furthermore, adenovirus encoded 4-1BBL expression has previously been successfully used to enhance responses toward Plasmodium falciparum and Influenza A antigens. We showed that the incorporation of 4-1BBL in the adenovirus vector led to surface expression of 4-1BBL on antigen presenting cells, but it did not enhance T cell responses in mice towards the Ii linked antigen. In tumor-bearing mice, our vaccine was found to decrease the frequency of TAA specific CD8+ T cells, but this difference did not alter the therapeutic efficacy. In order to reconcile our findings with the previous reports of increased anti-cancer efficacy using systemically delivered 4-1BB agonists, we incorporated a secreted version of 4 1BBL (Fc-4-1BBL) in our vaccine and co-expressed it with the Ii linked to TAA. In tumor bearing mice, this vaccine initially delayed tumor growth and slightly increased survival compared to the vaccine expressing the membrane form of 4 1BBL. Accordingly, secreted 4-1BBL co-encoded with the Ii linked antigen may offer a simplification compared to administration of drug and vaccine separately. PMID- 27004935 TI - Influence of the Cation Ratio on Optical and Electrical Properties of Amorphous Zinc-Tin-Oxide Thin Films Grown by Pulsed Laser Deposition. AB - Continuous composition spread (CCS) methods allow fast and economic exploration of composition dependent properties of multielement compounds. Here, a CCS method was applied for room temperature pulsed laser deposition (PLD) of amorphous zinc tin-oxide to gain detailed insight into the influence of the zinc-to-tin cation ratio on optical and electrical properties of this ternary compound. Our CCS approach for a large-area offset PLD process utilizes a segmented target and thus makes target exchange or movable masks in the PLD chamber obsolete. Cation concentrations of 0.08-0.82 Zn/(Zn + Sn) were achieved across single 50 * 50 mm(2) glass substrates. The electrical conductivity increases for increasing tin content, and the absorption edge shifts to lower energies. The free carrier concentration can be tuned from 10(20) to 10(16) cm(-3) by variation of the cation ratio from 0.1 to 0.5 Zn/(Zn + Sn). PMID- 27004936 TI - Constitutive aneuploidy and genomic instability in the single-celled eukaryote Giardia intestinalis. AB - Giardia intestinalis is an important single-celled human pathogen. Interestingly, this organism has two equal-sized transcriptionally active nuclei, each considered diploid. By evaluating condensed chromosome numbers and visualizing homologous chromosomes by fluorescent in situ hybridization, we determined that the Giardia cells are constitutively aneuploid. We observed karyotype inter-and intra-population heterogeneity in eight cell lines from two clinical isolates, suggesting constant karyotype evolution during in vitro cultivation. High levels of chromosomal instability and frequent mitotic missegregations observed in four cell lines correlated with a proliferative disadvantage and growth retardation. Other cell lines, although derived from the same clinical isolate, revealed a stable yet aneuploid karyotype. We suggest that both chromatid missegregations and structural rearrangements contribute to shaping the Giardia genome, leading to whole-chromosome aneuploidy, unequal gene distribution, and a genomic divergence of the two nuclei within one cell. Aneuploidy in Giardia is further propagated without p53-mediated cell cycle arrest and might have been a key mechanism in generating the genetic diversity of this human pathogen. PMID- 27004937 TI - Imaging multicellular specimens with real-time optimized tiling light-sheet selective plane illumination microscopy. AB - Despite the progress made in selective plane illumination microscopy, high resolution 3D live imaging of multicellular specimens remains challenging. Tiling light-sheet selective plane illumination microscopy (TLS-SPIM) with real-time light-sheet optimization was developed to respond to the challenge. It improves the 3D imaging ability of SPIM in resolving complex structures and optimizes SPIM live imaging performance by using a real-time adjustable tiling light sheet and creating a flexible compromise between spatial and temporal resolution. We demonstrate the 3D live imaging ability of TLS-SPIM by imaging cellular and subcellular behaviours in live C. elegans and zebrafish embryos, and show how TLS SPIM can facilitate cell biology research in multicellular specimens by studying left-right symmetry breaking behaviour of C. elegans embryos. PMID- 27004938 TI - Association Between Thrombophilic Gene Mutations and the Risk of Vascular Access Thrombosis in Hemodialysis Patients. AB - The cause of thrombosis in hemodialysis vascular access is considered to be of a multifactorial nature, including stenosis of the venous or arterial connection. Therefore, identification of relevant thrombotic risk factors could lead to an improved antithrombotic therapy. This case control study was performed to evaluate the relationship between Factor V (G1691A and A4070G) and Factor II polymorphisms and vascular access thrombosis in hemodialysis patients. One hundred and twenty-one patients undergoing dialysis were selected as subjects. This sample was divided into two groups; a case group of 60 patients who had sustained one or more thrombotic events that resulted in vascular access failure and a control group of 61 patients, who never had a thrombotic occlusion of a functioning permanent dialysis access. Our data demonstrated a significantly increased risk of vascular access thrombosis in carriers of the mutant FV (G1691A and A4070G) polymorphisms (P < 0.05).Further studies on a large-scale population and other genetic variants will be needed to find candidate genes for vascular access thrombosis in hemodialysis patients. PMID- 27004940 TI - Rethinking the Magnetic Resonance Imaging Findings in Early Rasmussen Encephalitis: A Case Report and Review of the Literature. AB - OBJECTIVE: We present a child with Rasmussen encephalitis and highlight the pitfalls of diagnosis when magnetic resonance imaging (MRI) is negative for atrophy. We review the literature regarding this issue, introduce the FreeSurfer software as a potential means of noninvasive diagnosis, and discuss methods for prompt and definitive treatment. METHODS: In addition to the patient description, we review the English language literature regarding pathologic diagnosis of Rasmussen encephalitis using the key words Rasmussen encephalitis, focal lesions, MRI, atrophy, epilepsia partialis continua and hemiparesis in PubMed. We conducted a retrospective, volumetric analysis of our patient's MRIs using FreeSurfer. RESULTS: Unlike the majority of patients in the literature with Rasmussen encephalitis, our patient's initial MRI was normal and later showed only a small area of T2 and fluid-attenuated inversion recovery high signal despite the presence of epilepsia partialis continua and a rapidly deteriorating clinical course. She did not meet the Rasmussen encephalitis diagnostic criteria until biopsy was obtained but is now seizure-free after functional hemispherotomy performed six months after her initial seizure. FreeSurfer analysis did not show cortical atrophy. CONCLUSION: The Bien criteria have poor sensitivity for the diagnosis of Rasmussen encephalitis when the MRI is negative for atrophy. Tissue diagnosis is essential in such instances. We suggest a high clinical index of suspicion and multidisciplinary collaboration between radiology, pathology, and neurosurgery to facilitate a greater emphasis on biopsy followed by hemispherotomy as definitive therapy for individuals with early Rasmussen encephalitis. PMID- 27004939 TI - Age-related changes in the effects of stress in pregnancy on infant motor development by maternal report: The Queensland Flood Study. AB - The current study examined the effects of a natural disaster (a sudden onset flood) as a stressor in pregnancy on infant fine and gross motor development at 2, 6, and 16 months of age. Whether the timing of the stressor in pregnancy or sex of the infant moderated the impact of the prenatal maternal stress on motor development was also explored. Mothers' objective experiences of the flood, emotional reactions and distress, and their cognitive appraisal of the event were assessed retrospectively. Infants' fine and gross motor skills were assessed with the Ages and Stages Questionnaire, and results showed age-related changes in the effects of prenatal maternal stress on these domains. At 2 months, higher levels of prenatal maternal stress was positively related to infant motor development, yet at 6 and 16 months of age there was a negative association, particularly if flood exposure occurred later in pregnancy and if mothers had negative cognitive appraisals of the event. Results also showed differential effects of the maternal stress responses to the floods on infants' fine and gross motor development at each age and that infant sex did not buffer these effects. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 640-659, 2016. PMID- 27004941 TI - [Atipical uremic hemolityc syndrome in pregnancy]. AB - Atypical haemolytic uraemic syndrome is one of the main variants of thrombotic microangiopathy, and is characterized by excessive complement activation in the microvasculature. It is also characterised by the clinical triad; non-immune haemolytic anaemia, thrombocytopenia, and acute renal failure. In addition, 60% of patients have mutations in the genes encoding complement regulators (factor H, factor I, membrane cofactor proteins, and thrombomodulin), activators (factor B and C3), as well as autoantibodies against factor H. Multiple factors are required for the disease to manifest itself, including a trigger and gene mutations with adequate penetration. Being one of the differential diagnoses of preeclampsia- eclampsia and HELLP syndrome means that the clinician must be familiar with the disease due to its high mortality, which can be modified with early diagnosis and comprehensive treatment. PMID- 27004942 TI - A novel client service quality measuring model and an eHealthcare mitigating approach. AB - OBJECTIVES: Facing population ageing in Hong Kong, the demand of long-term elderly health care services is increasing. The challenge is to support a good quality service under the constraints faced by recent shortage of nursing and care services professionals without redesigning the work flow operated in the existing elderly health care industries. the existing elderly health care industries. METHODS: RESULTS: The Total QoS measure based on Finite Capacity Queuing Model is a reliable method and an effective measurement for Quality of services. The value is good for measuring the staffing level and offers a measurement for efficiency enhancement when incorporate new technologies like ICT. The implemented system has improved the Quality of Service by more than 14% and the extra released manpower resource will allow clinical care provider to offer further value added services without actually increasing head count. CONCLUSIONS: We have developed a novel Quality of Service measurement for Clinical Care services based on multi-queue using finite capacity queue model M/M/c/K/n and the measurement is useful for estimating the shortage of staff resource in a caring institution. It is essential for future integration with the existing widely used assessment model to develop reliable measuring limits which allow an effective measurement of public fund used in health care industries. PMID- 27004943 TI - Identification of operculum and surgical results in endolymphatic sac drainage surgery. AB - To increase the accuracy of identification of the endolymphatic sac during endolymphatic sac drainage surgery, we focused on the intra-operative identification of the operculum as a structural marker of the endolymphatic sac and the vestibular aqueduct at the rugose portion. Then, we examined the relationship between identification of the operculum and surgical outcomes. We used 100 cases with intractable Meniere's disease who received endolymphatic sac drainage with local steroid administration, superior to traditional endolymphatic sac drainage surgery and non-surgical medical treatment. According to operation records, we divided these 100 cases into those with intra-operative identification of the operculum (n=72) and those without (n=28) and compared the surgical outcomes. The ratio of intra-operative identification of operculum (OPC(+)) was 72.0%. Better hearing results were observed significantly more often in patients with OPC(+), although there were no significant differences in vertigo results between OPC(+) and OPC(-). We concluded that the endolymphatic sac might be exposed adequately at rugose portion and opened for the drug delivery, resulting in better surgical results. PMID- 27004944 TI - Proliferation indices correlate with diagnosis and metastasis in diagnostically challenging melanocytic tumors. AB - The diagnosis of melanocytic lesions remains a formidable challenge in dermatopathology. For diagnostically challenging lesions, ancillary tests are available to inform the diagnosis, including immunohistochemistry and molecular testing (particularly fluorescence in situ hybridization [FISH]). However, the test result that most robustly informs the diagnosis remains controversial. Thirty-seven diagnostically challenging melanocytic lesions from our consultation service were reviewed. Histopathologic, immunohistochemical, and second generation FISH results (NeoGenomics; probes 6p25, 8q24, 11q13, 9p21, and centromere 9) were correlated with the final consensus diagnosis and clinical follow-up using logistic regression and Fisher exact test. Based on histopathologic and immunohistochemical features, cases were designated as "favor benign" (n=19) or "favor malignant" (n=18) by a consensus group of up to 7 dermatopathologists. The sensitivity of FISH for the diagnosis of melanoma was 39%, and the specificity was 84%. Univariate logistic regression models for a final diagnosis of melanoma showed that only increased Ki-67-positive dermal tumor cells (>=5%; P=.01) significantly correlated with the diagnosis of melanoma. FISH result did not correlate with the final diagnosis (melanoma or nevus; P=.26). Follow-up (range, 8-29months) was available for 35 cases (19 diagnosed as nevus and 16 as melanoma), and metastases (restricted to sentinel lymph nodes) were detected from 5 melanomas (3 FISH negative and 2 FISH positive). Only increased dermal mitotic figures (>1/mm(2)) correlated with metastases to sentinel lymph nodes (P=.04). Thus, in the classification of diagnostically challenging melanocytic lesions, indices of proliferation emerge as the most informative diagnostic adjuncts-correlating with diagnosis and clinical behavior, respectively. PMID- 27004945 TI - Comparison of Miller and Airtraq laryngoscopes for orotracheal intubation by physicians wearing CBRN protective equipment during infant resuscitation: a randomized crossover simulation study. AB - BACKGROUND: The purpose of this study was to evaluate the performance of orotracheal intubation with the Miller laryngoscope compared with the Airtraq laryngoscope by emergency and pediatric physicians wearing CBRN-PPE type III on infant manikins with conventional airway. We hypothesized that in this situation, the orotracheal intubation with the Airtraq laryngoscope would be faster and more effective than with the Miller laryngoscope. METHODS: This was a prospective, randomized, crossover, single-center study who recruited emergency department physicians on a voluntary basis. Each physician performed a total of 20 intubation trials while in CBRN-PPE with the two intubation techniques, Miller and Airtraq. Intubations by each airway device were tested over ten consecutive runs. The order of use of one or the other devices was randomized with a ratio of 1:1. The primary endpoint was overall orotracheal intubation success. RESULTS: Fifty-five emergency and pediatric physicians were assessed for eligibility. Forty-one physicians were included in this study and 820 orotracheal intubation attempts were performed. The orotracheal intubation success rate with the Airtraq laryngoscope was higher than with the Miller (99% vs. 92%; p-adjusted <.001). The orotracheal intubation and glottis visualization times decreased with the number of attempts (p <.001). The median orotracheal intubation time with the Airtraq laryngoscope was lower than with the Miller laryngoscope (15 s vs. 20 s; p adjusted <.001). The median glottis visualization time with the Airtraq laryngoscope and with the Miller laryngoscope were not different (6.0 s vs. 7.5 s; p-adjusted =.237). Thirty-four (83 %) physicians preferred the Airtraq laryngoscope versus 6 (15 %) for the Miller (p-adjusted <.001). DISCUSSION: For tracheal intubation by physicians wearing CBRN-PPE during infant resuscitation simulation, we showed that the orotracheal intubation success rate with the Airtraq laryngoscope was higher than with the Miller laryngoscope and that orotracheal intubation time with the Airtraq laryngoscope was lower than with the Miller laryngoscope. CONCLUSIONS: It seems useful to train the physicians in emergency departments in the use of pediatric Airtraq and for the management of CBRN risks. PMID- 27004946 TI - Factors in Etiology and Predisposition of Adult Tinea Capitis and Review of Published Literature. AB - BACKGROUND: Tinea capitis is a common fungal infection in children but is less frequently encountered in adults, especially in immunocompromised individuals. OBJECTIVES: To determine the incidence of tinea capitis in adults, the predisposing factors and causative species. METHODS: A retrospective study was conducted over a period of 5 years, from 2010 to 2015, on cases of tinea capitis diagnosed in the Department of Dermatology and Mycology Research Center in Tehran, Iran. The information was collected from the patients including age, gender, location of the lesions, results of direct examination and culture, cause of immunosuppression and the prescribed treatment. RESULTS: Twenty-five (20.6 %) patients (10 men and 15 women) with a mean age of 45.28 years were affected by tinea capitis among a total number of 121 positive cases. Most of these adults (80 %) had a grade of immunodeficiency due to the underlying syndromes or diseases, and the rest were immunocompetent. Trichophyton species were isolated from 84 % of these adult patients, indicating Trichophyton violaceum (T. violaceum) as the most common fungal agent. Treatment with oral terbinafine or itraconazole was successful in all these cases. CONCLUSIONS: The results showed that most cases affecting the adult population were caused by species of the genus Trichophyton. T. violaceum was the most common dermatophyte of adult patients. Thus, it is important to consider tinea capitis as a differential diagnosis in immunocompromised adults, even though it is considered to be rare in adults. PMID- 27004947 TI - Tongue volume in adults with skeletal Class III dentofacial deformities. AB - BACKGROUND: The size of the tongue is implicated as an essential etiological factor in the development of malocclusions. The aim of our study was to assess tongue size in skeletal Class III (SCIII) patients in comparison to adults with normal occlusion, using three-dimensional (3D) ultrasound. METHODS: The SCIII group consisted of 54 subjects; 34 females and 20 males and the control group contained 36 subjects, 18 from each gender with Class I relationship. 3D ultrasound images of the tongues were acquired, and then the tongues' volumes were assessed. RESULTS: The males in both the SCIII and control groups had significantly larger tongue volumes than the female subjects (mean SCIII 100.8 +/ 6.3 and control 92.4 +/- 9.8 cm(3) in males vs. SCIII 77.4 +/- 10.2 and control 67.2 +/- 5.6 cm(3) in females). The highly significantly larger tongue volumes were in SCIII patients of both genders (p were less than 0.01 for female and 0.03 for male). The tongue volumes within the whole SCIII group were significantly larger with more negative Wits values. CONCLUSION: The tongue volumes are significantly bigger in SCIII subjects than normal. Larger tongues correlate with more severe SCIII. The clinical importance of this data is that limited mandibular setback planning is necessary to prevent narrowing of respiratory airways. PMID- 27004948 TI - Phosphate limitation promotes unsaturated fatty acids and arachidonic acid biosynthesis by microalgae Porphyridium purpureum. AB - Polyunsaturated fatty acids (PUFAs) are highly appreciated on their nutritive value for human health and aquaculture. P. purpureum, one of the red microalgae acknowledged as a promising accumulator of ARA, was chosen as the target algae in the present research. Effects of sodium bicarbonate (0.04-1.2 g/L), temperature (25, 30 and 33 degrees C) and phosphate (0.00-0.14 g/L) on biomass yield, total fatty acids (TFA) and arachidonic acid (ARA) accumulation were investigated systemically. NaHCO3 dose of 0.8 g/L and moderate temperature of 30 degrees C were preferred. In addition, TFA and ARA production were significantly enhanced by an appropriate concentration of phosphate, and the highest TFA yield of 666.38 mg/L and ARA yield of 159.74 mg/L were obtained at a phosphate concentration of 0.035 g/L. Interestingly, with phosphate concentration continuing to fall, UFA/TFA and ARA/EPA ratios were increased accordingly, suggesting that phosphate limitation promoted unsaturated fatty acids and arachidonic acid biosynthesis. Low concentration of phosphate may be favored to increase the enzymatic activities of ?6-desaturase, which played a key role in catalyzing the conversion of C16:0 to C18:2, and thus the selectivity of UFA increased. Meanwhile, the increase of ARA selectivity could be attributed to omega6 pathway promotion and ?17-desaturase activity inhibition with phosphate limitation. Phosphate limitation strategy enhanced unsaturated fatty acids and ARA biosynthesis in P. purpureum, and can be applied in commercial scale manufacturing and commercialization of ARA. PMID- 27004949 TI - A Mixed Methods Study of Contraceptive Effectiveness in a Relationship Context Among Young Adult, Primarily Low-Income African American Women. AB - BACKGROUND: Unintended pregnancy is an important public health issue. Rates of unintended pregnancy are disproportionately higher among women from racial and ethnic minority groups among whom rates of contraceptive use are lower. Women's multifaceted feelings about pregnancy and perceptions of their intimate relationships may influence contraceptive behavior. METHODS: We used mixed methods to examine women's perceptions of pregnancy, motherhood, and contraceptives within the context of their intimate relationships. A convenience sample of 130 primarily low-income African American women ages 18-29 completed a cross-sectional, computerized survey; 12 women provided in-depth qualitative interview data. Generalized linear mixed models were used to identify associations between study variables and contraceptive effectiveness. Interview data were analyzed using qualitative descriptive methods and integrated with quantitative data. RESULTS: Higher positive pregnancy attitude [odds ratio (OR) 0.78; 95 % confidence interval (CI) 0.63, 0.98], lower contraceptive attitude (OR 1.17; 95 % CI 1.01, 1.36), and more than one recent sexual partner (OR 0.03; 95 % CI <0.01, 0.60) were associated with less effective contraceptive use. Qualitative results included three themes: You get pregnant that's on you; Motherhood means everything; and Make sure you're stable. Women's qualitative reports primarily supported but occasionally diverged from quantitative findings, reflecting discrepancies from their stated ideals, personal goals, and behavior. CONCLUSION: The incongruities between women's ideals and their actual contraceptive behavior demonstrate the complexity of making reproductive decisions based on existing life circumstances and challenges. Health care providers should have broad understanding of women's pregnancy goals in order to recommend the most appropriate contraceptive methods and pre-conception counseling. PMID- 27004950 TI - Prevalence and Risk for Negative Disability Outcomes Between American Indians Alaskan Natives and Other Race-Ethnic Groups in the Southwestern United States. AB - In the USA, some race-ethnic minorities are unjustly relegated to the margins of society. As a consequence, these groups are more frequently found to have risk profiles associated with adverse health than individuals from the majority group (non-Hispanic Whites). Limited research has been devoted to investigating how American Indians and Alaska Natives (AIANs) differ from other race-ethnic minorities and the majority group with regard to prevalence and risk for self care, independent living, and ambulatory disabilities. Our investigation attempts to quantify both of these tracks by accounting for race-ethnic and poverty status. Our cross-sectional analysis used nationally representative data from the American Community Survey (ACS) 5-year (2009-2013) Public Use Microdata Sample (PUMS) file to address this literature gap. We selected survey participants from the four states with the largest concentration of AIANs in the USA (Arizona, California, New Mexico, and Oklahoma). We used information on 2,428,233 individuals to generalize prevalence of and risk for disability to 49,994,332 individuals in the Southwest US. We found disability (self-reported) prevalence differed between our six race-ethnic groups in statistically significant and complex ways. Population-weighted logistic regression analyses adjusting for age, sex, and citizenship found AIANs have a higher risk for disability than non Hispanic Whites, non-Hispanic Asians, and Hispanics. In order to impact public health and build a more equitable society, efforts should continue to identify health disparities. Researchers should continue to advance conceptual frameworks on plausible causal mechanisms between markers of social stratification and disablement processes. PMID- 27004951 TI - Longitudinal Echocardiographic Evaluation of an Unusual Presentation of X-Linked Myxomatous Valvular Dystrophy Caused by Filamin A Mutation. AB - Polyvalvar myxomatous valve degeneration is a clinical pathology rarely encountered during cardiac anesthesia, but, when present, most commonly occurs in the context of a connective tissue disorder. Filamin A mutations have begun to be recognized as a source of progressive myxomatous mitral and tricuspid valve degeneration. These lesions can be diagnosed by echo, but their clinical presentation can be equivocal. We present a patient with significant echocardiographic findings of mitral and tricuspid valvar regurgitation, aortic dilatation, and intraoperative findings of aortic ectasia. In our case, a detailed family history led to a preoperative echocardiogram revealing myxomatous mitral and tricuspid valve degeneration with significant regurgitation and aortic dilatation. Genetic evaluation led to the diagnosis of a Filamin A mutation. Pre- and postrepair echocardiographic assessments of valvar function played a key role in the management of this patient. Continued surveillance of his aortic dilation and evaluation of postrepair valve function warrants close follow-up with a high likelihood for further surgical intervention. PMID- 27004952 TI - Health-related quality of life in thrombocytopenic patients with chronic hepatitis C with or without cirrhosis in the ENABLE-1 and ENABLE-2 studies. AB - BACKGROUND: Despite changes in the treatment paradigm towards non-interferon based therapies, interferon-based treatments are still used in some geographical regions for treating patients with hepatitis C virus (HCV) infection. Use of eltrombopag with interferon-based treatment for patients with thrombocytopenia and HCV was assessed in two similarly designed phase 3 trials (Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects With Hepatitis C-Related Liver Disease [ENABLE-1 and ENABLE-2]). These trials also aimed to determine whether response to antiviral therapy (e.g., sustained virologic response [SVR]) is associated with changes in health-related quality of life (HRQoL). This pooled, post-hoc analysis aimed to (1) determine whether or not specific aspects of clinical response to treatment (i.e., achieving SVR) are associated with a significant change in HRQoL, and (2) to determine the magnitude and direction of the association between important changes in HRQoL, clinical response to interferon-based therapy (e.g., SVR) and treatment (eltrombopag or placebo), and patient and disease attributes. METHODS: The Short-Form 36 Health Survey version 2 and Chronic Liver Disease Questionnaire-Hepatitis C Virus version were administered at various time points during the studies. Results from both trials were pooled for the analyses. Logistic regression analysis was used to assess the influence of 5 clinical factors (SVR, early virologic response [EVR], genotype [2/3 vs. non-2/3], treatment [eltrombopag or placebo], and cumulative interferon dose), plus other factors including ethnicity, model of end stage liver disease score, and platelets as predictors of meaningful changes in HRQoL. RESULTS: Between antiviral therapy baseline and the end of the 24-week post-treatment follow-up, declines in HRQoL were smaller in eltrombopag-treated patients than in placebo-treated patients, but the differences were not statistically significant. Mean changes among patients achieving SVR and EVR were small in comparison to thresholds of minimally important changes. Logistic models did not confirm the strength of the 5 clinical factors as predictors of meaningful changes in HRQoL during antiviral therapy, with the exception of the interaction between SVR and EVR (P = 0.0009). Asian ethnicity had a consistent effect on HRQoL, with East Asian patients being more likely to experience deterioration in HRQoL compared with white and/or other non-East Asian patients. CONCLUSIONS: While on active antiviral therapy, declines in HRQoL were not statistically different for eltrombopag-treated patients versus placebo-treated patients, suggesting that eltrombopag neither worsened HRQoL nor mitigated the effects of antiviral therapy on HRQoL. PMID- 27004953 TI - Bivalve immunity and response to infections: Are we looking at the right place? AB - Significant progress has been made in the understanding of cellular and molecular mediators of immunity in invertebrates in general and bivalve mollusks in particular. Despite this information, there is a lack of understanding of factors affecting animal resistance and specific responses to infections. This in part results from limited consideration of the spatial (and to some extent temporal) heterogeneity of immune responses and very limited information on host-pathogen (and microbes in general) interactions at initial encounter/colonization sites. Of great concern is the fact that most studies on molluscan immunity focus on the circulating hemocytes and the humoral defense factors in the plasma while most relevant host-microbe interactions occur at mucosal interfaces. This paper summarizes information available on the contrasting value of information available on focal and systemic immune responses in infected bivalves, and highlights the role of mucosal immune factors in host-pathogen interactions. Available information underlines the diversity of immune effectors at molluscan mucosal interfaces and highlights the tailored immune response to pathogen stimuli. This context raises fascinating basic research questions around host microbe crosstalk and feedback controls of these interactions and may lead to novel disease mitigation strategies and improve the assessment of resistant crops or the screening of probiotic candidates. PMID- 27004954 TI - Synthesis and evaluation of novel angiotensin II receptor 1 antagonists as anti hypertension drugs. AB - Three new angiotensin II receptor 1 antagonists, 1, 2 and 3 were designed, synthesized and evaluated. The AT1 receptor-binding assays in vitro showed that all the synthesized compounds had nanomolar affinity for the AT1 receptor. From which compound 3 was found to be the most potent ligands with an IC50 value of 2.67+/-0.23 nM. Biological evaluation in vivo revealed that all the compounds could cause significant decrease on MBP in a dose dependent manner in spontaneously hypertensive rats, and compound 3 especially showed an efficient and long-lasting effect in reducing blood pressure, whose maximal response lowered 41 mmHg of MBP at 10mg/kg and 62 mmHg at 15 mg/kg after oral administration, the significant anti-hypertensive effect lasted beyond 12 h, which is better than the reference compound losartan. The pharmacokinetic experiments showed that compound 3 could be absorbed efficiently and metabolized smoothly both in blood and in tissues in Wistar rats. The acute toxicity assay suggested that it has low toxicity with the LD50 value of 2974.35 mg/kg. These results demonstrate that compound 3 is a potent angiotensin AT1 receptor antagonist which could be considered as a novel anti-hypertension candidate and deserved for further investigation. PMID- 27004955 TI - Radiation-Induced Sarcoma: A 15-Year Experience in a Single Large Tertiary Referral Center. AB - PURPOSE: The purpose of this study is to report on the incidence and the experience in management of radiation-induced sarcoma (RIS) at a large single center in Korea for 15 years. MATERIALS AND METHODS: We retrospectively reviewed the sarcoma registry of a large institution from January 2000 to April 2014. RESULTS: Out of the 3,674 patients listed in the registry, 33 patients (0.9%) diagnosed with RIS were identified. The median latency of RIS was 12.1 years. The number of cases of RIS increased from four cases in the years 2000-2003 to 14 cases in the years 2012-2014. The most common histology was osteosarcoma (36.4%). The median follow-up period was 23.1 months, the median overall survival (OS) of all patients was 2.9 years, and their 5-year survival rate was 44.7%. Univariate and multivariate analyses showed association of the age at diagnosis (p=0.01) and the treatment aim (p=0.001) with the OS. The median OS and the 5-year survival rate of patients treated with curative surgery (n=19) were 9.6 years and 65%, respectively, and of the conservatively treated patients, 0.7 years and 0% (n=14). Re-irradiation was delivered to nine patients, and radiation toxicity was observed in five patients. CONCLUSION: In this study, RIS accounted for 0.9% of the cases of sarcoma, with increasing incidence. Despite the association of curative resection with increased survival, it could be applied to only 58% of the patients. Considering the limited treatment options for RIS, conduct of a genetic study to identify the underlying mechanism of RIS is needed. PMID- 27004956 TI - Chronological Changes of Quality of Life in Long-Term Survivors after Gastrectomy for Gastric Cancer. AB - PURPOSE: A few studies have prospectively evaluated changes in quality of life (QoL) after surgery in short-term survivors; however, no prospective study has evaluated the longitudinal changes in QoL in long-terms survivors. We prospectively evaluated the chronological changes in QoL after a gastrectomy over a 5-year postoperative period in a large group of patients. MATERIALS AND METHODS: QoL data from the European Organization for Research and Treatment of Cancer QLQ-C30 and the QLQ-STO22 questionnaires were obtained from 254 patients who completed the entire series of QoL assessments preoperatively and at 1, 2, 3, 4, and 5 years after surgery. RESULTS: There was no statistically significant change in global health status/QoL during the 5-year postoperative period. Decreases in QoL from upper gastrointestinal symptoms including diarrhea (p < 0.001), dysphagia (p < 0.001), reflux symptoms (p=0.029), and eating restrictions (p < 0.001) were observed among the long-term survivors. Decreased physical functioning (p < 0.001), role functioning (p < 0.001), and cognitive functioning (p < 0.001), along with fatigue (p=0.045) and a poor body image (p=0.003), negatively impacted the patients' QoL for a long time. CONCLUSION: Management of gastrointestinal symptoms should be specifically targeted as a part of long-term patient care after a gastrectomy. Proper nutritional care will improve food intake resulting in weight gain and improved physical functioning, role functioning, and body image. In addition, patients should be encouraged to preserve self-esteem and maintain social activity. PMID- 27004957 TI - Systematic examination of publicly-available information reveals the diverse and extensive corporate political activity of the food industry in Australia. AB - BACKGROUND: The political influence of the food industry, referred to as corporate political activity (CPA), represents a potential barrier to the development and implementation of effective public health policies for non communicable diseases prevention. This paper reports on the feasibility and limitations of using publicly-available information to identify and monitor the CPA of the food industry in Australia. METHODS: A systematic search was conducted for information from food industry, government and other publicly-available data sources in Australia. Data was collected in relation to five key food industry actors: the Australian Food and Grocery Council; Coca Cola; McDonald's; Nestle; and Woolworths, for the period January 2012 to February 2015. Data analysis was guided by an existing framework for classifying CPA strategies of the food industry. RESULTS: The selected food industry actors used multiple CPA strategies, with 'information and messaging' and 'constituency building' strategies most prominent. CONCLUSIONS: The systematic analysis of publicly available information over a limited period was able to identify diverse and extensive CPA strategies of the food industry in Australia. This approach can contribute to accountability mechanisms for NCD prevention. PMID- 27004958 TI - Absent words and the (dis)similarity analysis of DNA sequences: an experimental study. AB - BACKGROUND: An absent word with respect to a sequence is a word that does not occur in the sequence as a factor; an absent word is minimal if all its factors on the other hand occur in that sequence. In this paper we explore the idea of using minimal absent words (MAW) to compute the distance between two biological sequences. The motivation and rationale of our work comes from the potential advantage of being able to extract as little information as possible from large genomic sequences to reach the goal of comparing sequences in an alignment-free manner. FINDINGS: We report an experimental study on the use of absent words as a distance measure among biological sequences. We provide recommendations to use the best index based on our analysis. In particular, our analysis reveals that the best performers are: the length weighted index of relative absent word sets, the length weighted index of the symmetric difference of the MAW sets, and the Jaccard distance between the MAW sets. We also found that during the computation of the absent words, the reverse complements of the sequences should also be considered. CONCLUSION: The use of MAW to compute the distance between two biological sequences has potential advantage over alignment based methods. It is expected that this potential advantage would encourage researchers and practitioners to use this as a (dis)similarity measure in the context of sequence comparison and phylogeny reconstruction. Therefore, we present here a comparison among different possible models and indexes and pave the path for the biologists and researchers to choose an appropriate model for such comparisons. PMID- 27004959 TI - Food IgG4 antibodies are elevated not only in children with wheat allergy but also in children with gastrointestinal diseases. AB - BACKGROUND: Food sIgG and sIgG4 are highly individually versatile. We put a hypothesis that one of the responsible factors is the presence of gastrointestinal inflammatory diseases. The objectives were: 1. An analysis of wheat and rice sIgG and sIgG4 in healthy children, children with IgE-mediated wheat allergy (WA), coeliac disease (CD) and Helicobacter pylori infection (HP). 2. Usability of wheat sIgG and sIgG4 in the WA diagnostics. METHODS: We compared 388 each wheat and rice sIgG and sIgG4 in a group of 200 children: 50 WA (diagnosis, diet treatment, tolerance), 50 CD (diagnosis and remission), 50 HP and 50 healthy. SIgE, sIgG, sIgG4 were determined with the FEIA method (Pharmacia CAP System). RESULTS: In healthy children food sIgG were the lowest; no sIgG4 were found. In the CD diagnosis group wheat and rice sIgG and rice sIgG4 were the most common and their concentrations were the highest (p < .001, p < .05). Wheat sIgG4 were the highest in WA children (diagnosis and tolerance) to fall during the elimination diet (p < .05). Wheat and rice sIgG remained the same in all allergy phases. Rice sIgG also did not differ in the class G4. CONCLUSIONS: 1. Serum concentrations of wheat and rice sIgG and sIgG4 are elevated in children with CD, HP and WA. 2. Sub-clinical incidence of some gastrointestinal inflammatory diseases may be responsible for high individual versatility of food sIgG and sIgG4 concentrations in serum. 3. Wheat sIgG and sIgG4 in children do not correlate with WA clinical picture. PMID- 27004960 TI - Pitfalls of Doppler Measurements for Arterial Blood Flow Quantification in Small Animal Research: A Study Based on Virtual Ultrasound Imaging. AB - High-resolution Doppler is a popular tool for evaluating cardiovascular physiology in mutant mice, though its 1-D nature and spectral broadening processes complicate interpretation of the measurement. Hence, it is crucial for pre-clinical researchers to know how error sources in Doppler assessments reveal themselves in the murine arterial system. Therefore, we performed virtual Doppler experiments in a computer model of an aneurysmatic murine aorta with full control of the imaging and insonified fluid dynamics. We observed significant variability in Doppler performance and derived vascular indices depending on the interrogated flow, operator settings and signal processing. In particular, we found that (i) Doppler spectra in the upper aortic branches and celiac artery exhibited more broadening because of complex out-of-beam flow paths; (ii) mean frequency tracking outperforms tracking of the outer envelope, but is sensitive to errors in angle correction; and (iii) imaging depths deviating much from the elevation focus suffer from decreased spectral quality. PMID- 27004961 TI - Differential roles of estrogen receptors, ESR1 and ESR2, in adult rat spermatogenesis. AB - Estrogens, through their receptors, play an important role in regulation of spermatogenesis. However, the precise role of the estrogen receptors (ESR1 and ESR2) has been difficult to determine as in vivo estradiol treatment would signal through both the ESRs. Hence we had developed in vivo selective ESR agonist administration models in adult male rats to decipher the individual roles of the ESRs. Treatment with both ESR1 and ESR2 agonists decreased sperm counts after 60 days of treatment. The present study aimed to delineate the precise causes of decreased sperm counts following treatment with the two ESR agonists. Treatment with ESR1 agonist causes an arrest in differentiation of round spermatids into elongated spermatids, mainly due to down-regulation of genes involved in spermiogenesis. ESR2 agonist administration reduces sperm counts due to spermiation failure and spermatocyte apoptosis. Spermiation failure observed is due to defects in tubulobulbar complex formation because of decrease in expression of genes involved in actin remodelling. The increase in spermatocyte apoptosis could be due to increase in oxidative stress and decrease in transcripts of anti-apoptotic genes. Our results suggest that the two ESRs regulate distinct aspects of spermatogenesis. ESR1 is mainly involved with regulation of spermiogenesis, while ESR2 regulates spermatocyte apoptosis and spermiation. Activation of estrogen signaling through either of the receptors can affect their respective processes during spermatogenesis and lead to low sperm output. Since many environmental estrogens can bind to the two ESRs with different affinities, these observations can be useful in understanding their potential effects on spermatogenesis. PMID- 27004962 TI - Association between epicardial adipose tissue volume and myocardial salvage in patients with a first ST-segment elevation myocardial infarction: An epicardial adipose tissue paradox. AB - BACKGROUND: Epicardial adipose tissue (EAT), defined as the adipose tissue between the visceral pericardium and the outer margin of the myocardium, is associated with coronary artery disease in the general population. However, the clinical implications of EAT in patients with ST-segment elevation myocardial infarction (STEMI) remain unclear. METHODS: A total of 142 patients with a first STEMI, who received reperfusion therapy within 12h from symptom onset, were enrolled. All patients underwent cardiac magnetic resonance imaging to evaluate infarct core (Core), area at risk (AAR), and EAT volume. Myocardial salvage index (MSI) was defined as AAR minus Core divided by AAR. Patients in the lower tertile of EAT volume were classified as the low EAT group (group L) and the other two thirds as the high EAT group (group H). RESULTS: The mean MSI was lower in group L than in group H (0.43+/-0.13 vs 0.49+/-0.13, p=0.01), and the mean extent of Core was higher in group L than in group H (25+/-10% vs 19+/-10%, p<0.01). Multivariate linear regression analysis including coronary risk factors and previously reported predictors of infarct size demonstrated that EAT volume was an independent predictor of MSI (beta coefficient=0.002 per 1mL, p=0.002). CONCLUSIONS: A lower EAT volume is associated with less myocardial salvage and larger infarct size in patients with a first STEMI. PMID- 27004963 TI - Author's reply. AB - BACKGROUND: We sometimes experience the regression of left ventricular hypertrabeculation (LVHT), which is compatible with the diagnosis of LV non compaction cardiomyopathy (LVNC) in adult patients. However, little is known about the association between LVHT regression and LV systolic function in adult patients. METHODS: We prospectively examined 23 consecutive adult patients who fulfilled the echocardiographic criteria for LVNC. LV reverse remodeling (RR) was defined as an absolute increase in LV ejection fraction of >10% at 6 months follow-up. LVHT area was calculated by subtraction from the outer edge to the inner edge of the LVHT at end-systole. RESULTS: The mean follow-up period was 61 months. LVRR was observed in 9 patients (39%). The changes in the mean LVHT area showed significant correlation with the changes in LV ejection fraction (r=-0.78, P<0.0001). Cardiac death occurred in 7 patients (50%) without LVRR, but no patients with LVRR died (log-rank, P=0.003). Furthermore, composite of cardiac death and hospitalization of heart failure occurred in 10 patients (71%) without LVRR, whereas there was one patient with LVRR (log-rank, P<0.001). CONCLUSIONS: Regression of LVHT is associated with improvement in LV systolic function. LVRR might be associated with a favorable prognosis in patients with LVHT. PMID- 27004965 TI - Left atrial volume: To thread a round and round maze. PMID- 27004964 TI - Regression of left ventricular hypertrabeculation/noncompaction. PMID- 27004966 TI - Clinical characteristics of patients hospitalized for acute heart failure according to hospital arrival timing. AB - BACKGROUND: Whether clinical characteristics and outcomes in patients suffering acute heart failure (AHF) vary according to the timing of hospital arrival is unclear. We aimed to evaluate differences between subjects presenting in the daytime and nighttime. METHODS: A total of 679 patients with AHF were examined, classified into the two groups from the viewpoint of hospital arrival period into daytime (n=370; 8am-6pm) and nighttime (n=309; 6pm-8am). RESULTS: The prevalence of malnutrition and longer pre-hospital delay (>=48h) were greater, whereas a previous history of myocardial infarction, proportion of arrival by ambulance, and the frequency of New York Heart Association class IV symptoms, as well as systolic and diastolic blood pressure, and heart rate were lower in subjects presenting in the daytime. Patients with malnutrition defined as 5>=of the Controlling Nutrition Status scores demonstrate a longer pre-hospital delay compared to those without (34.2% vs. 19.9%, p<0.05). There was no significant difference in the 30-day outcomes but length of stay was significantly longer in subjects presenting in the daytime than in the nighttime. Multivariable logistic regression analysis revealed that systolic blood pressure, malnutrition, and chronic kidney disease were significantly related to prolonged length of stay. CONCLUSIONS: Our present results suggest that patients with AHF who present in the daytime may have higher rate of malnutrition status and lower systolic blood pressure compared to those presenting in the nighttime. PMID- 27004968 TI - Assessment of the needs of mothers and primary healthcare providers to support early childhood development in Egypt: a qualitative study. AB - BACKGROUND: The early childhood period is considered the most important developmental phase in an individual's lifespan. However, it is not addressed in the Egyptian health system. We aimed to explore mothers' and healthcare providers' perceptions about early childhood development (ECD) and identify their needs to support ECD in Egypt. METHODS: Focus group discussions with 79 mothers of children younger than 2 years old from different socio-economic backgrounds and residing in urban and rural areas and 26 primary healthcare providers were used to collect data. Emerging themes and subthemes were identified from the data analysis. RESULTS: Urban and rural mothers in Egypt of all educational levels are not well prepared to support their children's early development, especially the cognitive and emotional aspects. Limited sources of information about ECD, the large families of rural women and an absence of developmental health services and family support were the most important factors that led to a neglect of mother child communication and stimulation. CONCLUSION: Raising community awareness and training primary healthcare providers to counsel mothers about ECD are important prerequisites for supporting ECD in Egypt. Rural and first-time mothers would be the most valuable starting point. PMID- 27004967 TI - Capturing the ephemeral human pluripotent state. AB - During human development, pluripotency is present only in early stages of development. This ephemeral cell potential can be captured in vitro by obtaining pluripotent stem cells (PSC) with self-renewal properties, the human embryonic stem cells (hESC). However, diverse studies suggest the existence of a plethora of human PSC (hPSC) that can be derived from both embryonic and somatic sources, depending on defined culture conditions, their spatial origin, and the genetic engineering used for reprogramming. This review will focus on hPSC, covering the conventional primed hESC, naive-like hPSC that resemble the ground-state of development, region-selective PSC, and human induced PSC (hiPSC). We will analyze differences and similarities in their differentiation potential as well as in the molecular circuitry of pluripotency. Finally, we describe the need for human feeder cells to derive and maintain hPSC, because they could emulate the interaction of in vivo pluripotent cells with extraembryonic structures that support development. Developmental Dynamics 245:762-773, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004969 TI - Pregnant Women Diet Quality and Its Sociodemographic Determinants in Southwestern Bangladesh. AB - BACKGROUND: Diet diversity of pregnant women is associated with nutrition sufficiency, micronutrient adequacy, and pregnancy outcomes. However, the sociodemographic determinants of diet diversity among pregnant women in low income countries are not well studied. OBJECTIVE: The analysis was undertaken to study the determinants of high dietary diversity and consumption of micronutrient rich foods by pregnant women from rural Bangladesh. METHODS: Pregnant women (508) were randomly selected from southwestern Bangladesh and interviewed to collect data about diet and sociodemographic characteristics. A 24-hour recall was used to collect information about diet. Diet diversity score was calculated for 9 major food groups. All analyses were conducted using STATA SE 12. RESULT: The overall mean diet diversity score was low at 4.28 and was significantly high among pregnant women who have higher educational achievement, whose husbands' occupation was business, who live in households of 4 or more family members, and who were dwelling in a house with more than 1 room. Highest gap on knowledge and consumption was reported for 3 food groups including dairy foods, eggs, and dark green leafy vegetables. Consumption of dairy and eggs was lower among women from low socioeconomic status, but no significant association was found between sociodemographic characteristics and consumption of leafy vegetables. CONCLUSION: Our analysis has shown that diet quality of pregnant women was poor and intake of micronutrient-rich foods was low despite having knowledge about the importance of these foods, underscoring the need for promoting the diet quality in developing countries through behavior change communication programs. PMID- 27004971 TI - Uniting to end the TB epidemic: advances in disease control from prevention to better diagnosis and treatment. AB - Tuberculosis is a major global cause of morbidity and mortality. Despite recent advances in containing the epidemic, several challenges continue to slow progress towards elimination including the continuing impact of drug resistant disease, and the lack of appropriate tools. Curtailing the transmission of tuberculosis remains a challenge especially in high burden countries. New developments in measuring correlates of protection are urgently needed to support the evaluation of vaccines. Similarly, despite progress in molecular diagnostics, better tools are required to identify resistance to antibiotics in multi and extensively drug resistant tuberculosis. Whole Genome Sequencing may lead to the next generation of assays to rapidly detect resistance and evaluate transmission. Advances on shortening treatment are hampered by the lack of a biomarker of cure which obviates the current long wait for relapses in trials. New research is urgently needed to support development of new vaccines and better diagnostics tools and shorter treatment for drug sensitive and resistant tuberculosis. PMID- 27004970 TI - Nutrient Intake in Vietnamese Preschool and School-Aged Children is Not Adequate: The Role of Dairy. AB - BACKGROUND: The traditional Vietnamese diet carries the risk of micronutrient deficiencies, and a substantial part of children <11 years do not meet the Vietnamese recommended dietary allowance (RDA) for a range of nutrients. Dairy products are known for their high nutrient density and milk in particular for its provision of high-quality protein and relevant concentrations of calcium, magnesium, vitamin B2, vitamin B12, and pantothenic acid. OBJECTIVE: The present study aimed to evaluate the contribution of dairy to the overall nutrient intakes in the diets of Vietnamese children and to gain insight into factors affecting dairy consumption. METHODS: Food intake, including dairy, was assessed by a 24 hour recall in 2811 Vietnamese children clustered into 4 age-groups: 1.0 to 2.9, 3.0 to 5.9, 6.0 to 8.9, and 9.0 to 11.9 years, and dairy was categorized into 6 product groups based on available information in the Vietnamese food composition table. RESULTS: Higher dairy intake was associated with significantly higher intakes (in % estimated average requirement and %RDA) of all assessed nutrients, and largest effects and strongest associations were found for vitamin B2, calcium, vitamin D, fat, vitamin B1, protein, vitamin A, and zinc. Age, area of residence, and wealth status influenced the consumption of dairy products. Furthermore, age also influenced nutrient intake adequacy, which was generally lower at older age, especially after the age of 6 years. CONCLUSION: The nutrient composition of the diet in especially Vietnamese school-aged children requires attention, and (fortified) dairy can play an important role in this. PMID- 27004972 TI - Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey. AB - Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). PMID- 27004975 TI - Symposium on Primate Ecomorphology: introduction. PMID- 27004973 TI - Corneal Epithelium Thickness Profile in 614 Normal Chinese Children Aged 7-15 Years Old. AB - The purpose of the study is to describe the values and distribution of corneal epithelium thickness (CET) in normal Chinese school-aged children, and to explore associated factors with CET. CET maps were measured by Fourier-domain optical coherence tomography (FD-OCT) in normal Chinese children aged 7 to 15 years old from two randomly selected schools in Shanghai, China. Children with normal intraocular pressure were further examined for cycloplegic autorefraction, corneal curvature radius (CCR) and axial length. Central (2-mm diameter area), para-central (2- to 5-mm diameter area), and peripheral (5- to 6-mm diameter area) CET in the superior, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal cornea; minimum, maximum, range, and standard deviation of CET within the 5-mm diameter area were recorded. The CET was thinner in the superior than in the inferior and was thinner in the temporal than in the nasal. The maximum CET was located in the inferior zone, and the minimum CET was in the superior zone. A thicker central CET was associated with male gender (p = 0.009) and older age (p = 0.037) but not with CCR (p = 0.061), axial length (p = 0.253), or refraction (p = 0.351) in the multiple regression analyses. CCR, age, and gender were correlated with para-central and peripheral CET. PMID- 27004974 TI - Long-Term Restoration of Thymidine Phosphorylase Function and Nucleoside Homeostasis Using Hematopoietic Gene Therapy in a Murine Model of Mitochondrial Neurogastrointestinal Encephalomyopathy. AB - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a metabolic disorder caused by mutations in TYMP, encoding thymidine phosphorylase (TP). In MNGIE patients, TP dysfunction produces systemic thymidine and deoxyuridine accumulation, which ultimately impairs mitochondrial DNA replication and results in mitochondrial dysfunction. To date, only allogeneic hematopoietic stem cell transplantation has demonstrated long-term clinical efficacy, but high morbidity and mortality associated with this procedure necessitate the search for safer alternatives. In a previous study, we demonstrated that hematopoietic stem cell gene therapy using a lentiviral vector containing the coding sequence of TYMP restored the biochemical homeostasis in an animal model of MNGIE. In the present follow-up study, we show that ectopic expression of TP in the hematopoietic system restores normal nucleoside levels in plasma, as well as in tissues affected in MNGIE such as small intestine, skeletal muscle, brain, and liver. Mitochondrial dNTP pool imbalances observed in liver of the animal model were also corrected by the treatment. The biochemical effects were maintained at least 20 months even with low levels of chimerism. No alterations in the blood cell counts or other toxic effects were observed in association with the lentiviral transduction or TP overexpression. These results further support the notion that gene therapy is a feasible treatment option for MNGIE. PMID- 27004977 TI - John William Simmons Harris (1926-2013). PMID- 27004976 TI - Why are there apes? Evidence for the co-evolution of ape and monkey ecomorphology. AB - Apes, members of the superfamily Hominoidea, possess a distinctive suite of anatomical and behavioral characters which appear to have evolved relatively late and relatively independently. The timing of paleontological events, extant cercopithecine and hominoid ecomorphology and other evidence suggests that many distinctive ape features evolved to facilitate harvesting ripe fruits among compliant terminal branches in tree edges. Precarious, unpredictably oriented, compliant supports in the canopy periphery require apes to maneuver using suspensory and non-sterotypical postures (i.e. postures with eccentric limb orientations or extreme joint excursions). Diet differences among extant species, extant species numbers and evidence of cercopithecoid diversification and expansion, in concert with a reciprocal decrease in hominoid species, suggest intense competition between monkeys and apes over the last 20 Ma. It may be that larger body masses allow great apes to succeed in contest competitions for highly desired food items, while the ability of monkeys to digest antifeedant-rich unripe fruits allows them to win scramble competitions. Evolutionary trends in morphology and inferred ecology suggest that as monkeys evolved to harvest fruit ever earlier in the fruiting cycle they broadened their niche to encompass first more fibrous, tannin- and toxin-rich unripe fruits and later, for some lineages, mature leaves. Early depletion of unripe fruit in the central core of the tree canopy by monkeys leaves a hollow sphere of ripening fruits, displacing antifeedant-intolerant, later-arriving apes to small-diameter, compliant terminal branches. Hylobatids, orangutans, Pan species, gorillas and the New World atelines may have each evolved suspensory behavior independently in response to local competition from an expanding population of monkeys. Genetic evidence of rapid evolution among chimpanzees suggests that adaptations to suspensory behavior, vertical climbing, knuckle-walking, consumption of terrestrial piths and intercommunity violence had not yet evolved or were still being refined when panins (chimpanzees and bonobos) and hominins diverged. PMID- 27004979 TI - Field-based experimental water footprint study of sunflower growth in a semi-arid region of China. AB - BACKGROUND: Field-scale changes in the water footprint during crop growth play an important role in formulating sustainable water utilisation strategies. This study aimed to explore field-scale variation in the water footprint of growing sunflowers in the western Jilin Province, China, during a 3-year field experiment. The goals of this study were to (1) determine the components of the 'blue' and 'green' water footprints for sunflowers sown with water, and (2) analyse variations in water footprints and soil water balance under different combinations of temperature and precipitation. Specific actions could be adopted to maintain sustainable agricultural water utilisation in the semi-arid region based on this study. RESULTS: The green, blue, and grey water footprints accounted for 93.7-94.7%, 0.4-0.5%, and 4.9-5.8%, respectively, of the water footprint of growing sunflowers. The green water footprint for effective precipitation during the growing season accounted for 58.8% in a normal drought year but 48.2% in an extreme drought year. When the effective precipitation during the growing season could not meet the green water use, a moisture deficit arose. This increase in the moisture deficit can have a significant impact on soil water balance. CONCLUSION: Green water was the primary water source for sunflower growth in the study area, where a scarcity of irrigation water during sunflower growth damaged the soil water balance, particularly in years with continuous drought. The combination of temperature and precipitation effected the growing environment, leading to differences in yield and water footprint. The field experiments in this area may benefit from further water footprint studies at the global, national and regional scale. (c) 2016 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID- 27004978 TI - Glycobiology simplified: diverse roles of glycan recognition in inflammation. AB - Glycans and complementary glycan-binding proteins are essential components in the language of cell-cell interactions in immunity. The study of glycan function is the purview of glycobiology, which has often been presented as an unusually complex discipline. In fact, the human glycome, composed of all of its glycans, is built primarily from only 9 building blocks that are combined by enzymes (writers) with specific and limited biosynthetic capabilities into a tractable and increasingly accessible number of potential glycan patterns that are functionally read by several dozen human glycan-binding proteins (readers). Nowhere is the importance of glycan recognition better understood than in infection and immunity, and knowledge in this area has already led to glycan mimetic anti-infective and anti-inflammatory drugs. This review includes a brief tutorial on human glycobiology and a limited number of specific examples of glycan-binding protein-glycan interactions that initiate and regulate inflammation. Examples include representatives from different glycan-binding protein families, including the C-type lectins (E-selectin, P-selectin, dectin-1, and dectin-2), sialic acid-binding immunoglobulin-like lectins (sialic acid binding immunoglobulin-like lectins 8 and 9), galectins (galectin-1, galectin-3, and galectin-9), as well as hyaluronic acid-binding proteins. As glycoscience technologies advance, opportunities for enhanced understanding of glycans and their roles in leukocyte cell biology provide increasing opportunities for discovery and therapeutic intervention. PMID- 27004980 TI - Response to a pilot single-centre randomized trial: the PATRASTOM trial. PMID- 27004981 TI - Preterm cranial ultrasound scanning is both feasible and effective in a middle income country. AB - AIM: Cranial ultrasound is seldom used in middle-income countries, and the burden of preterm brain injury and its relationship to perinatal data is unknown. We assessed cranial ultrasound abnormalities in very low-birthweight (VLBW) infants and correlated the findings with perinatal data. METHODS: VLBW Armenian infants receiving neonatal intensive care in 2012 were scanned from birth to term equivalent age (TEA). Clinical data were collected prospectively. RESULTS: We studied 100 VLBW infants with a median gestation of 30 weeks. Periventricular white matter echogenicity (PVE) lasting more than two weeks was seen in 34 infants, grade III intraventricular haemorrhage (IVH) in 10, haemorrhagic parenchymal infarction (HPI) in seven and cystic periventricular leukomalacia in two. Caudothalamic notch echogenicity appeared in 36 infants after two to three weeks, with cystic transformation in 22. At TEA, 17 infants had persisting PVEs and 55 had increased basal ganglia/thalamic (BGT) echogenicity. Lack of antenatal steroids was significantly associated with IVH and HPI and intubation at birth with IVH. Late BGT echogenicity was generally seen in infants without perinatal problems. CONCLUSION: Our study demonstrated that cranial ultrasound can be used effectively in a middle-income country to identify high-risk infants and monitor quality of care. PMID- 27004982 TI - Ether and siloxane functionalized ionic liquids and their mixtures as electrolyte for lithium-ion batteries. AB - The present study deals with an investigation of two novel imidazolium ionic liquids bearing ether-ether (1O2O2-Im-2O1) or ether-siloxane (1O2O2-Im-1SiOSi) functionalities with TFSI anion and their mixtures with propylene carbonate as electrolytes in lithium-ion batteries. The electrochemical stability and conductivity of these novel ILs were analyzed by electrochemical studies, such as cyclic voltammetry, linear sweep voltammetry and impedance measurements. The applicability of these ILs as electrolytes in Li-ion batteries was studied in the presence of a high concentration of LiTFSI (1 mol kg(-1) electrolyte) and the ether-ether IL was shown to possess a high electrochemical stability window (ESW) of 5.9 V and good conductivity of 2.2 mS cm(-1). The electrochemical stability and conductivity were further complimented by self-diffusion of different ions using pulsed gradient spin-echo (PGSE) NMR, viscosity and thermal properties like TGA and DSC analysis. More importantly, we explored the effect of temperature on the electrochemical stability and conductivity of these ILs by electrochemical impedance spectroscopy. PMID- 27004984 TI - Survival Benefit From Kidney Transplantation Using Kidneys From Deceased Donors Aged >=75 Years: A Time-Dependent Analysis. AB - Patients with end-stage renal disease have longer survival after kidney transplantation than they would by remaining on dialysis; however, outcome with kidneys from donors aged >=75 years and the survival of recipients of these organs compared with their dialysis counterparts with the same probability of obtaining an organ is unknown. In a longitudinal mortality study, 2040 patients on dialysis were placed on a waiting list, and 389 of them received a first transplant from a deceased donor aged >=75 years. The adjusted risk of death and survival were calculated by non-proportional hazards analysis with being transplanted as a time-dependent effect. Projected years of life since placement on the waiting list was almost twofold higher for transplanted patients. Nonproportional adjusted risk of death after transplantation was 0.44 (95% confidence interval [CI] 0.61-0.32; p < 0.001) in comparison with those that remained on dialysis. Stratifying by age, adjusted hazard ratios for death were 0.17 (95% CI 0.47-0.06; p = 0.001) for those aged <65 years, 0.56 (95% CI 0.92 0.34; p = 0.022) for those aged 65-69 years and 0.82 (95% CI 1.28-0.52; p = 0.389) for those aged >=70 years. Although kidney transplantation from elderly deceased donors is associated with reduced graft survival, transplanted patients have lower mortality than those remaining on dialysis. PMID- 27004983 TI - Alterations in pharmacological and behavioural responses in recombinant mouse line with an increased predisposition to catalepsy: role of the 5-HT1A receptor. AB - BACKGROUND AND PURPOSE: One important syndrome of psychiatric disorders in humans is catalepsy. Here, we created mice with different predispositions to catalepsy and analysed their pharmacological and behavioural properties. EXPERIMENTAL APPROACH: Two mouse lines, B6-M76C and B6-M76B, were created by transfer of the main locus of catalepsy containing the 5-HT1A receptor gene to the C57BL/6 genetic background. Behaviour, brain morphology, expression of key components of the serotoninergic system, and pharmacological responses to acute and chronic stimulation of the 5-HT1A receptor were compared. KEY RESULTS: B6-M76B mice were not cataleptic, whereas 14% of B6-M76C mice demonstrated catalepsy and decreased depressive-like behaviour. Acute administration of the 5-HT1A receptor agonist 8 OH-DPAT resulted in dose-dependent hypothermia and in decreased locomotion in both lines. Chronic 8-OH-DPAT administration abolished the 5-HT1A receptor mediated hypothermic response in B6-M76C mice and increased locomotor activity in B6-M76B mice. In addition, 5-HT metabolism was significantly reduced in the hippocampus of B6-M76C mice, and this effect was accompanied by an increased expression of the 5-HT1A receptor. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that transfer of the main locus of hereditary catalepsy containing the 5 HT1A receptor from CBA mice to the C57BL/6 genetic background led to increased postsynaptic and decreased presynaptic functional responses of the 5-HT1A receptor. This characteristic establishes the B6-M76C line as an attractive model for the pharmacological screening of 5-HT1A receptor-related drugs specifically acting on either pre- or postsynaptic receptors. LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc. PMID- 27004985 TI - Cannabis policy and the uptake of treatment for cannabis-related problems. AB - INTRODUCTION AND AIMS: We examine public health effects of steps towards more permissive cannabis policies introduced in Belgium, Finland, France and Portugal between 1999 and 2004. Public health effects are captured in terms of cannabis induced treatment uptake as reported by the European Monitoring Centre for Drugs and Drug Addiction. DESIGN AND METHODS: We use a quasi-experimental difference-in differences design drawing on observational data. RESULTS: While the number of clients with primary cannabis problems per reporting treatment unit has generally increased, this increase does not seem to be substantially stronger in the countries that introduced more permissive cannabis policies. DISCUSSION AND CONCLUSIONS: The specific reforms carried out in the group of reforming countries can thus not be shown to have had adverse effects on public health in terms of treatment uptake. PMID- 27004987 TI - Interaction of COMT rs4680 and BDNF rs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults. AB - As modulators of dopamine availability and release in the brain, COMT and BDNF polymorphisms have demonstrated interactions on human cognition; however, the underlying neural mechanisms remain largely unknown. In this study, we aimed to investigate the interactions of COMT rs4680 and BDNF rs6265 on global functional connectivity density (gFCD) of the brain in 265 healthy young subjects. We found a significant COMT * BDNF interaction on the gFCD in the left frontal eye field (FEF), showing an inverted U-shape modulation by the presumed dopamine signaling. This finding was consistently repeated in the gFCD analyses using other four connection thresholds. Our findings reveal a COMT * BDNF interaction on the FCD in the left FEF, which may be helpful for understanding the neural mechanisms of the COMT * BDNF interactions on the FEF-related cognitive functions. Hum Brain Mapp 37:2468-2478, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004986 TI - New Findings in eNOS gene and Thalidomide Embryopathy Suggest pre-transcriptional effect variants as susceptibility factors. AB - Antiangiogenic properties of thalidomide have created an interest in the use of the drug in treatment of cancer. However, thalidomide is responsible for thalidomide embryopathy (TE). A lack of knowledge regarding the mechanisms of thalidomide teratogenesis acts as a barrier in the aim to synthesize a safer analogue of thalidomide. Recently, our group detected a higher frequency of alleles that impair the pro-angiogenic mechanisms of endothelial nitric oxide synthase (eNOS), coded by the NOS3 gene. In this study we evaluated variable number tandem repeats (VNTR) functional polymorphism in intron 4 of NOS3 in individuals with TE (38) and Brazilians without congenital anomalies (136). Haplotypes were estimated for this VNTR with previously analyzed polymorphisms, rs2070744 (-786C > T) and rs1799983 (894T > G), in promoter region and exon 7, respectively. Haplotypic distribution was different between the groups (p = 0.007). Alleles -786C (rs2070744) and 4b (VNTR), associated with decreased NOS3 expression, presented in higher frequency in TE individuals (p = 0.018; OR = 2.57; IC = 1.2-5.8). This association was not identified with polymorphism 894T > G (p = 0.079), which influences eNOS enzymatic activity. These results suggest variants in NOS3, with pre-transcriptional effects as susceptibility factors, influencing the risk TE development. This finding generates insight for a new approach to research that pursues a safer analogue. PMID- 27004989 TI - The standard map: From Boltzmann-Gibbs statistics to Tsallis statistics. AB - As well known, Boltzmann-Gibbs statistics is the correct way of thermostatistically approaching ergodic systems. On the other hand, nontrivial ergodicity breakdown and strong correlations typically drag the system into out of-equilibrium states where Boltzmann-Gibbs statistics fails. For a wide class of such systems, it has been shown in recent years that the correct approach is to use Tsallis statistics instead. Here we show how the dynamics of the paradigmatic conservative (area-preserving) stan-dard map exhibits, in an exceptionally clear manner, the crossing from one statistics to the other. Our results unambiguously illustrate the domains of validity of both Boltzmann-Gibbs and Tsallis statistical distributions. Since various important physical systems from particle confinement in magnetic traps to autoionization of molecular Rydberg states, through particle dynamics in accelerators and comet dynamics, can be reduced to the standard map, our results are expected to enlighten and enable an improved interpretation of diverse experimental and observational results. PMID- 27004988 TI - Crystal structure of the vicilin from Solanum melongena reveals existence of different anionic ligands in structurally similar pockets. AB - Crystal structure of a vicilin, SM80.1, was determined towards exploring its possible physiological functions. The protein was purified from Solanum melongena by combination of ammonium sulphate fractionation and size exclusion chromatography. Structure was determined ab initio at resolution of 1.5 A by X ray crystallography showing the three-dimensional topology of the trimeric protein. Each monomer of SM80.1 consists of two similar domains with hydrophobic binding pocket and each accommodating different ligands, i.e. acetate and pyroglutamate. The relatively high stability of these independent anionic ligands in similar pockets indicated a strict requirement of stabilization by hydrogen bonds with the charged residues, suggesting a degree of plasticity within the binding pocket. Comparison of SM80.1 structure with those of other 7S vicilins indicated conservation of putative binding pocket for anionic ligands. Here we propose the possibility of trapping of these ligands in the protein for their requirement in the metabolic processes. PMID- 27004991 TI - The reliability of a single protocol to determine endothelial, microvascular and autonomic functions in adolescents. AB - BACKGROUND: Impairments in macrovascular, microvascular and autonomic function are present in asymptomatic youths with clustered cardiovascular disease risk factors. This study determines the within-day reliability and between-day reliability of a single protocol to non-invasively assess these outcomes in adolescents. METHODS: Forty 12- to 15-year-old adolescents (20 boys) visited the laboratory in a fasted state on two occasions, approximately 1 week apart. One hour after a standardized cereal breakfast, macrovascular function was determined via flow-mediated dilation (FMD). Heart rate variability (root mean square of successive R-R intervals; RMSSD) was determined from the ECG-gated ultrasound images acquired during the FMD protocol prior to cuff occlusion. Microvascular function was simultaneously quantified as the peak (PRH) and total (TRH) hyperaemic response to occlusion in the cutaneous circulation of the forearm via laser Doppler imaging. To address within-day reliability, a subset of twenty adolescents (10 boys) repeated these measures 90 min afterwards on one occasion. RESULTS: The within-day typical error and between-day typical error expressed as a coefficient of variation of these outcomes are as follows: ratio-scaled FMD, 5.1% and 10.6%; allometrically scaled FMD, 4.4% and 9.4%; PRH, 11% and 13.3%; TRH, 29.9% and 23.1%; and RMSSD, 17.6% and 17.6%. The within- and between-day test-retest correlation coefficients for these outcomes were all significant (r > 0.54 for all). CONCLUSION: Macrovascular, microvascular and autonomic functions can be simultaneously and non-invasively determined in adolescents using a single protocol with an appropriate degree of reproducibility. Determining these outcomes may provide greater understanding of the progression of cardiovascular disease and aid early intervention. PMID- 27004990 TI - High prevalence of clinically unsuspected dengue disease among children in Ribeirao Preto city, Brazil. AB - The aim of this study was to analyze the characteristics of Dengue virus (DENV) infected children and the accuracy of dengue diagnosis based on clinical presentations. The inclusion criteria were children >=1-year-old presenting febrile illness with 1-7 days of onset. Children (n = 110) aged 2-15 years were included in this study. DENV infection was confirmed with virological tests using serum, salvia, and/or urine samples. The attending pediatricians classified 56/110 (50.91%) of the children as suspected dengue cases. The DENV infection was confirmed by specific laboratory tests in 52/56 (92.9%) of the suspected dengue cases but also in 44/54 (81.5%) of the unsuspected dengue cases; total of 96/110 (87.27%) confirmed dengue cases. The clinical diagnosis gave an overall sensitivity of 54.2% (52/96) and a specificity of 71.4% (10/14). The positive predictive value of the clinical diagnosis was 92.8% and negative predictive value was 18.5%. After the third day of onset of symptoms, the DENV genome detection rate was similar in serum and saliva samples, suggesting that saliva samples represent an alternative to blood samples for early dengue diagnosis. Vaccination against Yellow fever virus did not influence the antibody response against DENV-1, DENV-2, and DENV-3, which circulated during the study period. Although the signs and symptoms were compatible with dengue, the attending pediatricians did not suspect the disease in several children. Therefore, the inclusion of virological tests for early diagnosis in the protocols for dengue surveillance would help in the implementation of prompt treatment of patients and epidemic containment strategies. J. Med. Virol. 88:1711-1719, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27004992 TI - Chemoselective synthesis of functional homocysteine residues in polypeptides and peptides. AB - A methodology was developed for efficient, chemoselective transformation of methionine residues into stable, functional homocysteine derivatives. Methionine residues can undergo highly chemoselective alkylation reactions at low pH to yield stable sulfonium ions, which could then be selectively demethylated to give stable alkyl homocysteine residues. This mild, two-step process is chemoselective, efficient, tolerates many functional groups, and provides a means for creation of new functional biopolymers, site-specific peptide tagging, and synthesis of biomimetic and structural analogs of peptides. PMID- 27004993 TI - Evaluation of SMARTube to Detect HIV Infection Before Seroconversion Using Standard Methods. AB - The acute phase of HIV infection carries substantial risk of transmission; identification of acute-phase infections may offer opportunities to reduce that risk. SMARTube incubation of blood specimens is designed to stimulate in vivo primed HIV-specific lymphocytes to produce HIV antibodies in vitro. The resulting supernatant (S-plasma) can be tested to identify acute infections with commercially available HIV assays. We assessed the performance of the SMARTube to identify acute HIV infections in studies at three developing country sites. We conducted HIV incidence studies in Ho Chi Minh City, Vietnam, and Bloemfontein and Rustenburg, South Africa. We estimated HIV incidence in cross-sectional samples and measured prospective incidence in uninfected women followed for up to 12 months. We incorporated SMARTube into the HIV testing algorithm at cross sectional screening and monthly follow-up visits. We tested 1,384 persons in Vietnam, 1,145 women in Bloemfontein, and 538 persons in Rustenburg. Cross sectional samples from 11 participants that tested positive with SMARTube after an initial unincubated negative test result (11 of 2,472; 0.4% of all specimens) were considered "potential acute" infections. Matching samples from 3 of the 11 (27.3%) were confirmed by polymerase chain reaction (PCR) testing. In follow-up of 355, 401, and 223 uninfected women in Vietnam, Bloemfontein, and Rustenburg, respectively, 11 seroconversions occurred in Bloemfontein and Rustenburg. In four of these incident infections (36.4%), SMARTube testing had resulted in earlier detection of HIV infection than the eventual seroconversion visits. In our field studies, pretreatment with SMARTube allowed the identification of acute HIV-1 infection in some new infections, but with a positive predictive value of 27%. Larger studies are needed to evaluate SMARTube as an alternative to technically challenging and costly enzyme immunoassay and PCR testing to detect acute HIV infection. PMID- 27004994 TI - Serine suppresses the motor function of a periplasmic PomB mutation in the Vibrio flagella stator. AB - The flagellar motor of Vibrio alginolyticus is made of two parts: a stator consisting of proteins PomA and PomB, and a rotor whose main component is FliG. The interaction between FliG and PomA generates torque for flagellar rotation. Based on cross-linking experiments of double-Cys mutants of PomB, we previously proposed that a conformational change in the periplasmic region of PomB caused stator activation. Double-Cys mutants lost their motility due to an intramolecular disulfide bridge. In this study, we found that the addition of serine, a chemotactic attractant, to a PomB(L160C/I186C) mutant restored motility without cleaving the disulfide bridge. We speculate that serine changed the rotor (FliG) conformation, affecting rotational direction. Combined with the counterclockwise (CCW)-biased mutation FliG(G214S), motility of PomB(L160C/I186C) was restored without the addition of serine. Likewise, motility was restored without serine in Che(-) mutants, in either a CCW-locked or clockwise (CW)-locked strain. In contrast, in a DeltacheY (CCW-locked) strain, Vibrio (L160C/I186C) required serine to be rescued. We speculate that CheY affects stator conformation and motility restoration by serine is independent on the chemotaxis signaling pathway. PMID- 27004996 TI - Transport properties through hexagonal boron nitride clusters embedded in graphene nanoribbons. AB - First-principles calculations are employed in the study of the electronic and quantum transport properties of hexagonally shaped boron nitride (h-BN) clusters embedded in either zigzag or armchair graphene nanoribbons. Chemical doping of the h-BN cluster was taken into consideration by using carbon atoms to replace either the boron (B27N24C3) or the nitrogen (B27N24C3) sites in the central ring. While the quantum conductance of the system with zigzag edges is found to be spin dependent, it was observed that the system with an armchair edge requires an electron imbalance in order to show a spin-dependent conductance. Furthermore, the possibility of molecular adsorption onto these doped systems is studied. The effects of the attached molecules to the quantum conductance shows the potential of these hybrid systems for molecular sensing applications. PMID- 27004995 TI - Hydrophilic CeO2 nanocubes protect pancreatic beta-cell line INS-1 from H2O2 induced oxidative stress. AB - Oxidative stress plays a key role in the occurrence and development of diabetes. With their unique redox properties, CeO2 nanoparticles (nanoceria) exhibit promising potential for the treatment of diabetes resulting from oxidative stress. Here, we develop a novel preparation of hydrophilic CeO2 nanocubes (NCs) with two different sizes (5 nm and 25 nm) via an acetate assisted hydrothermal method. Dynamic light scattering, zeta potential measurements and thermogravimetric analyses were utilized to investigate the changes in the physico-chemical characteristics of CeO2 NCs when exposed to in vitro cell culture conditions. CCK-8 assays revealed that the CeO2 NCs did not impair cell proliferation in the pancreatic beta-cell line INS-1 at the highest dose of 200 MUg mL(-1) over the time scale of 72 h, while being able to protect INS-1 cells from H2O2-induced cytotoxicity even after protein adsorption. It is also noteworthy that nanoceria with a smaller hydrodynamic radius exhibit stronger antioxidant and anti-apoptotic effects, which is consistent with their H2O2 quenching capability in biological systems. These findings suggest that nanoceria can be used as an excellent antioxidant for controlling oxidative stress-induced pancreatic beta-cell damage. PMID- 27004997 TI - Omega-3 fatty acid supplementation for expectant mothers with depressive symptoms in Japan and Taiwan: An open-label trial. PMID- 27004998 TI - The new Landsat 8 potential for remote sensing of colored dissolved organic matter (CDOM). AB - Due to a combination of factors, such as a new coastal/aerosol band and improved radiometric sensitivity of the Operational Land Imager aboard Landsat 8, the atmospherically-corrected Surface Reflectance product for Landsat data, and the growing availability of corrected fDOM data from U.S. Geological Survey gaging stations, moderate-resolution remote sensing of fDOM may now be achievable. This paper explores the background of previous efforts and shows preliminary examples of the remote sensing and data relationships between corrected fDOM and Landsat 8 reflectance values. Although preliminary results before and after Hurricane Sandy are encouraging, more research is needed to explore the full potential of Landsat 8 to continuously map fDOM in a number of water profiles. PMID- 27004999 TI - Temporal scales for nearshore hits of current-driven pollution in the Gulf of Finland. AB - Lagrangian trajectories of water parcels reconstructed using the TRACMASS model from three-dimensional velocity fields by the RCO model for 1965-2004 are used to analyse the temporal scales and the probability for the hits to the nearshore by pollution originating from a major fairway in the Gulf of Finland and transported by surface currents. Increasing the simulation length from 10 to 20days induces a linear increase in particle age, but the pattern of nearshore hits remains the same. A reasonable benefit can be reached by relatively small shifts of certain parts of the present fairway in a few locations. The overall probabilities do not reveal any trend for 1965-2004. The largest changes in the nearshore hits are revealed for the proportion of hits to the opposite nearshore areas. This feature probably reflects an abrupt turn of the geostrophic air-flow over the southern Baltic Sea by ~40 degrees since 1987. PMID- 27005000 TI - GMC can continue to strike off doctors who miss hearings, appeal court rules. PMID- 27005001 TI - Modelling of the frictional behaviour of the snake skin covered by anisotropic surface nanostructures. AB - Previous experimental data clearly revealed anisotropic friction on the ventral scale surface of snakes. However, it is known that frictional properties of the ventral surface of the snake skin range in a very broad range and the degree of anisotropy ranges as well to a quite strong extent. This might be due to the variety of species studied, diversity of approaches used for the friction characterization, and/or due to the variety of substrates used as a counterpart in the experiments. In order to understand the interactions between the nanostructure arrays of the ventral surface of the snake skin, this study was undertaken, which is aimed at numerical modeling of frictional properties of the structurally anisotropic surfaces in contact with various size of asperities. The model shows that frictional anisotropy appears on the snake skin only on the substrates with a characteristic range of roughness, which is less or comparable with dimensions of the skin microstructure. In other words, scale of the skin relief should reflect an adaptation to the particular range of surfaces asperities of the substrate. PMID- 27005002 TI - Incorporation of Inter-Subject Information to Improve the Accuracy of Subject Specific P300 Classifiers. AB - Although the inter-subject information has been demonstrated to be effective for a rapid calibration of the P300-based brain-computer interface (BCI), it has never been comprehensively tested to find if the incorporation of heterogeneous data could enhance the accuracy. This study aims to improve the subject-specific P300 classifier by adding other subject's data. A classifier calibration strategy, weighted ensemble learning generic information (WELGI), was developed, in which elementary classifiers were constructed by using both the intra- and inter-subject information and then integrated into a strong classifier with a weight assessment. 55 subjects were recruited to spell 20 characters offline using the conventional P300-based BCI, i.e. the P300-speller. Four different metrics, the P300 accuracy and precision, the round accuracy, and the character accuracy, were performed for a comprehensive investigation. The results revealed that the classifier constructed on the training dataset in combination with adding other subject's data was significantly superior to that without the inter subject information. Therefore, the WELGI is an effective classifier calibration strategy which uses the inter-subject information to improve the accuracy of subject-specific P300 classifiers, and could also be applied to other BCI paradigms. PMID- 27005003 TI - Impact of the Great East Japan Earthquake on Regional Obstetrical Care in Miyagi Prefecture. AB - OBJECTIVES: The authors report the results of surveys on the emergency transport or evacuation status of obstetric patients conducted in Miyagi prefecture, one of the major disaster areas of the Great East Japan Earthquake and tsunami. METHODS: The surveys examined the damages to maternity institutions, evacuation status and transport of pregnant women, and prehospital childbirths and were conducted in 50 maternity institutions and 12 fire departments in Miyagi. RESULTS: Two coastal institutions were destroyed completely, and four institutions were destroyed partially by the tsunami, forcing them to stop medical services. In the two-month period after the disaster, 217 pregnant women received hospital transport or gave birth after evacuation. Satisfactory perinatal outcomes were maintained. Emergency obstetric transport increased to approximately 1.4 fold the number before the disaster. Twenty-three women had prehospital childbirths, indicating a marked increase to approximately three times the number of the previous year. CONCLUSION: In the acute phase of the tsunami disaster, maternity institutions were damaged severely and perinatal transport was not possible; as a result, pregnant women inevitably gave birth in unplanned institutions, and the number of prehospital births was increased extremely. To obtain satisfactory obstetric outcomes, it is necessary to construct a future disaster management system and to re-recognize pregnant women as people with special needs in disaster situations. Sugawara J , Hoshiai T , Sato K , Tokunaga H , Nishigori H , Arai T , Okamura K , Yaegashi N . Impact of the Great East Japan Earthquake on regional obstetrical care in Miyagi Prefecture. Prehosp Disaster Med. 2016;31(3):255- 258. PMID- 27005004 TI - Improved confidence intervals for the linkage disequilibrium method for estimating effective population size. AB - The linkage disequilibrium method is currently the most widely used single sample estimator of genetic effective population size. The commonly used software packages come with two options, referred to as the parametric and jackknife methods, for computing the associated confidence intervals. However, little is known on the coverage performance of these methods, and the published data suggest there may be some room for improvement. Here, we propose two new methods for generating confidence intervals and compare them with the two in current use through a simulation study. The new confidence interval methods tend to be conservative but outperform the existing methods for generating confidence intervals under certain circumstances, such as those that may be encountered when making estimates using large numbers of single-nucleotide polymorphisms. PMID- 27005005 TI - Pharmacokinetic profile of methotrexate in psoriatic skin via the oral or subcutaneous route using dermal microdialysis showing higher methotrexate bioavailability in psoriasis plaques than in non-lesional skin. AB - AIMS: The aim of this pilot study was to use microdialysis to evaluate levels of Methotrexate (MTX) directly in psoriatic skin following oral or subcutaneous administration of MTX to elaborate a complete pharmacokinetic profile within the dermal skin. METHODS: Six patients with chronic plaque psoriasis on the arm undergoing treatment with MTX were included in a mono-centre clinical trial. Patients were under treatment with p.o. or s.c. MTX (7.5 and 15 mg) for at least 3 months. Interstitial fluid was collected ex vivo via dermal microdialysis from lesional or non-lesional skin and via intravenous microdialysis as well as blood serum every hour up to 10 h after methotrexate administration every hour. MTX was analysed via liquid chromatography. RESULTS: The area under the curve (AUC) of methotrexate from peripheral blood was up to four times higher than from microdiaylsis, which detection of free unbound MTX. The AUC from dialysates in psoriatic lesional skin was higher than in non-lesional psoriatic skin, and the AUC levels from i.v. microdialysis were non-significantly higher than those from lesional psoriatic skin. Pharmacokinetic profiles were individually quite different and did not primarily depend on the dose or the means (p.o. vs. s.c.) in which it was administered. CONCLUSION: Dermal microdialysis is a valid tool to evaluate levels of methotrexate in the skin of psoriasis patients. Drug levels and bioavailability of methotrexate were higher in lesional than non-lesional psoriatic skin. The individual AUC of MTX was not primarily dependent on the route or dose of administration. PMID- 27005006 TI - Evaluation of magnetic matrix solid-phase dispersion for the determination of polychlorinated biphenyls in water samples by gas chromatography with electron capture detection. AB - A vortex-assisted magnetic matrix solid-phase dispersion method was proposed for the determination of polychlorinated biphenyls in different matrix water samples by gas chromatography with electron capture detection. Magnetic bamboo charcoal (MBC) was synthesized for the adsorption of polychlorinated biphenyls in water samples. Complete separation of the liquid phase and the solid magnetic bamboo charcoal was easily achieved by using a permanent magnet. Under the optimized conditions, good linearity in the range of 0.006-5.0 MUg/L was obtained with regression coefficients (r) higher than 0.9986. Based on a signal-to-noise ratio of 3, limits of detection were found to be 0.001-0.003 MUg/L. Relative standard deviations ranged from 2.92 to 6.56%. Relative recoveries were 96.6-111.2% for the spiked wastewater sample and 90.7-104.7% for the spiked lake water sample. All results showed that the proposed method was simple, sensitive, and reliable for the determination of polychlorinated biphenyls in water samples. PMID- 27005007 TI - Subcutaneous regular insulin for the treatment of diabetic ketoacidosis in children. AB - BACKGROUND: Diabetic ketoacidosis (DKA) treatment protocols vary, however low dose intravenous administration of regular insulin is the standard care for replacing insulin in most centers. Few studies, the majority in adults, demonstrated subcutaneous injection of rapid-acting insulin every 1-2 hours to be a valid alternative. OBJECTIVE: To evaluate the efficacy and safety of subcutaneous regular insulin administered every 4 hours in pediatric DKA in a clinical setting. METHODS: A retrospective chart review was conducted. Charts of all children treated with subcutaneous regular insulin for DKA and pH >= 7.0, between 2007 and 2010, were reviewed. Seventy-six DKA episodes in 52 patients were included. Data regarding clinical characteristics, response to treatment, and the occurrence of complications were analyzed. DKA episodes in patients with new-onset diabetes and in those with established diabetes were compared. RESULTS: Mean age was 11.6 +/- 4.0 yr. Eighteen episodes occurred in children with new onset diabetes. In all episodes, our protocol resulted in recovery from DKA. Median time to DKA resolution (pH > 7.30, HCO3 > 15) was 10.3 (5.5, 14.2) h. The median total insulin dose was 0.05 (0.04, 0.06) (unit/kg/h). During DKA treatment, hypoglycemia occurred in one episode and hypokalemia, mostly mild, was documented in 14. No cardiac arrhythmias, incidents of cerebral edema, or mortality occurred. CONCLUSION: Subcutaneous regular insulin administered every 4 hours is an effective and safe alternative for the insulin treatment of DKA with pH > 7.0 in children. Such treatment has the potential to simplify insulin administration when compared to either intravenous regular insulin or q1-2 hour subcutaneous rapid insulin and reduce both patient inconvenience and admission costs. PMID- 27005009 TI - Muscle analysis using pQCT, DXA and MRI. AB - Skeletal muscle is one of the larger organs of the body and is integrally involved in metabolic processes in both health and disease. The ability to accurately and precisely measure skeletal muscle structure is essential for understanding the changes that occur naturally over the lifespan as well as those observed in chronic disease, and in response to targeted interventions. Musculoskeletal imaging allows for the quantification of skeletal muscle mass and select modalities are also able to determine muscle quality. The purpose of this paper is to review peripheral quantitative computed tomography (pQCT), dual X-ray energy absorptiometry (DXA) and magnetic resonance imaging (MRI) techniques used to assess skeletal muscle size and quality in-vivo. Each modality is briefly described and the strengths and limitations are provided. No single imaging technique will be able to best address every clinical and research question of interest. Selecting the most appropriate imaging device for measuring skeletal muscle depends on access to technology, availability of expertise required for image acquisition and analysis, characteristics of the population, anatomical site of interest, and the level of structural detail required. PMID- 27005008 TI - The ATP-dependent RNA helicase HrpB plays an important role in motility and biofilm formation in Xanthomonas citri subsp. citri. AB - BACKGROUND: RNA helicases are enzymes that catalyze the separation of double stranded RNA (dsRNA) using the free energy of ATP binding and hydrolysis. DEAD/DEAH families participate in many different aspects of RNA metabolism, including RNA synthesis, RNA folding, RNA-RNA interactions, RNA localization and RNA degradation. Several important bacterial DEAD/DEAH-box RNA helicases have been extensively studied. In this study, we characterize the ATP-dependent RNA helicase encoded by the hrpB (XAC0293) gene using deletion and genetic complementation assays. We provide insights into the function of the hrpB gene in Xanthomonas citri subsp. citri by investigating the roles of hrpB in biofilm formation on abiotic surfaces and host leaves, cell motility, host virulence of the citrus canker bacterium and growth in planta. RESULTS: The hrpB gene is highly conserved in the sequenced strains of Xanthomonas. Mutation of the hrpB gene (?hrpB) resulted in a significant reduction in biofilms on abiotic surfaces and host leaves. ?hrpB also exhibited increased cell dispersion on solid medium plates. ?hrpB showed reduced adhesion on biotic and abiotic surfaces and delayed development in disease symptoms when sprayed on susceptible citrus leaves. Quantitative reverse transcription-PCR assays indicated that deletion of hrpB reduced the expression of four type IV pili genes. The transcriptional start site of fimA (XAC3241) was determined using rapid amplification of 5'-cDNA Ends (5'RACE). Based on the results of fimA mRNA structure predictions, the fimA 5' UTR may contain three different loops. HrpB may be involved in alterations to the structure of fimA mRNA that promote the stability of fimA RNA. CONCLUSIONS: Our data show that hrpB is involved in adherence of Xanthomonas citri subsp. citri to different surfaces. In addition, to the best of our knowledge, this is the first time that a DEAH RNA helicase has been implicated in the regulation of type IV pili in Xanthomonas. PMID- 27005010 TI - High-sensitivity acoustic sensors from nanofibre webs. AB - Considerable interest has been devoted to converting mechanical energy into electricity using polymer nanofibres. In particular, piezoelectric nanofibres produced by electrospinning have shown remarkable mechanical energy-to electricity conversion ability. However, there is little data for the acoustic-to electric conversion of electrospun nanofibres. Here we show that electrospun piezoelectric nanofibre webs have a strong acoustic-to-electric conversion ability. Using poly(vinylidene fluoride) as a model polymer and a sensor device that transfers sound directly to the nanofibre layer, we show that the sensor devices can detect low-frequency sound with a sensitivity as high as 266 mV Pa( 1). They can precisely distinguish sound waves in low to middle frequency region. These features make them especially suitable for noise detection. Our nanofibre device has more than five times higher sensitivity than a commercial piezoelectric poly(vinylidene fluoride) film device. Electrospun piezoelectric nanofibres may be useful for developing high-performance acoustic sensors. PMID- 27005011 TI - First intercomparison among laboratories involved in COST Action-TU1301 "NORM4Building": Determination of natural radionuclides in ceramics. AB - This work describes the outcomes of the COST Action-TU1301 "NORM4Building" intercomparison on the determination of natural radioactivity in ceramics. Twenty two laboratories involved in the intercomparison are evaluated for their performance using robust statistics. The reference values of 226Ra (214Bi and 214Pb) are determined to be 122 +/- 11 Bq kg-1 and 124 +/- 14 Bq kg-1, respectively and in secular equilibrium in the uranium chain while the reference values of 232Th (228Ac) is determined to be 61 +/- 6 Bq kg-1 and that of 40K was determined to be 955 +/- 40 Bq kg-1. Although the aim of the exercise was to determine the activity concentration of 226Ra, 232Th and 40K and evaluation of the "Activity Concentration Index", laboratories were asked to report complete characterization of natural radionuclides. The results of this exercise pointed out a good performance among laboratories since the percentage of the acceptable results were above 90% for the radionuclides of interest. Based on these results, considering the systematic rejection of the results reported from a few laboratories we emphasize the need for quality control procedures. PMID- 27005012 TI - Severe abdominal pain in a patient with Zika infection: A case in Risaralda, Colombia. PMID- 27005014 TI - Incarceration or mandatory treatment: Drug use and the law in the Middle East and North Africa. AB - In the Middle East and North Africa (MENA), drug policies are embedded in the prohibition paradigm. Laws and legislation criminalize all types of activities related to illicit drugs. This article gives a detailed assessment of the provisions of Arab national laws to control the use of illicit drugs across the areas of punishment of drug users, penalties for drug dependence, legislation on use and dependence treatment, and the right of the convicted people who use drugs to confidentiality. It reviews the national legislations on drug control of 16 Arab countries as amended in January 2011. PMID- 27005015 TI - Assessment of myocardial fibrosis with T1 mapping MRI. AB - Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present. PMID- 27005016 TI - Manual adjustment of tube voltage from 120 to 100 kVp during abdominal CT in patients with body weights <=75 kg: assessment of image quality and radiation dose in a prospective, randomised trial. AB - AIM: To assess image quality and radiation dose in patients with body weights <=75 kg undergoing abdominal computed tomography (CT) with a tube voltage of either 120 or 100 kVp. MATERIALS AND METHODS: Eighty patients weighing <=75 kg were prospectively assigned to receive either 120 or 100 kVp abdominal CT in the portal-venous phase. Attenuation values of abdominal organs and image noise were measured, and the contrast-to-noise ratios (CNRs) were calculated. Subjective image quality was assessed by three independent radiologists. Radiation exposure was assessed by size-specific dose estimate (SSDE). RESULTS: The mean attenuation of the kidney increased by 20% at 100 kVp (p<0.0001), and the mean image noise was 27% higher in the 100 kVp (p=0.003). The CNR did not significantly differ between the groups (120 kVp, 6.6+/-2.8; 100 kVp, 7.4+/-3.6; p=0.26). Except for subjective image noise (p<0.001), no other subjective quality parameters (e.g., contrast, artefacts) were significantly different between the two groups (p between 0.094 and 0.761). The mean SSDE in the 100-kVp group (9.8+/-1.8 mGy) was reduced by 19% compared to the 120-kVp group (12.1+/-1.8 mGy; p<0.0001). CONCLUSION: Manual reduction of tube voltage from the standard 120 to 100 kVp for portal-venous phase CT in patients with body weights <=75 kg resulted in a 19% dose reduction while maintaining objective and subjective image quality. PMID- 27005013 TI - The outer-membrane export signal of Porphyromonas gingivalis type IX secretion system (T9SS) is a conserved C-terminal beta-sandwich domain. AB - In the recently characterized Type IX Secretion System (T9SS), the conserved C terminal domain (CTD) in secreted proteins functions as an outer membrane translocation signal for export of virulence factors to the cell surface in the Gram-negative Bacteroidetes phylum. In the periodontal pathogen Porphyromonas gingivalis, the CTD is cleaved off by PorU sortase in a sequence-independent manner, and anionic lipopolysaccharide (A-LPS) is attached to many translocated proteins, thus anchoring them to the bacterial surface. Here, we solved the atomic structure of the CTD of gingipain B (RgpB) from P. gingivalis, alone and together with a preceding immunoglobulin-superfamily domain (IgSF). The CTD was found to possess a typical Ig-like fold encompassing seven antiparallel beta strands organized in two beta-sheets, packed into a beta-sandwich structure that can spontaneously dimerise through C-terminal strand swapping. Small angle X-ray scattering (SAXS) revealed no fixed orientation of the CTD with respect to the IgSF. By introducing insertion or substitution of residues within the inter domain linker in the native protein, we were able to show that despite the region being unstructured, it nevertheless is resistant to general proteolysis. These data suggest structural motifs located in the two adjacent Ig-like domains dictate the processing of CTDs by the T9SS secretion pathway. PMID- 27005017 TI - Utility of additional abdominopelvic CT in detecting occult cancer in patients with unprovoked venous thromboembolism. AB - AIM: To analyse the positive rate for cancer on additional abdominopelvic computed tomography (CT) in patients with unprovoked venous thromboembolism (VTE), evaluate the subsequent emergence of a cancer diagnosis in the clinical follow-up period, and identify any possible predictive factors of cancer in this cohort, which may allow better selection of patients for additional imaging. MATERIALS AND METHODS: Consecutive adult patients with VTE were retrospectively identified in two large teaching hospitals between January 2013 and June 2014, including a subset of those with unprovoked VTE. Relevant demographic data were extracted and analysed. All patients had a minimum of 12 months clinicoradiological follow-up. RESULTS: One thousand four hundred and forty-six patients with VTE were deemed eligible, of which 699 (48%) were male; the median age (range) was 66 (16-102) years. The prevalence of pre-existing cancer in these patients was 343/1446 (24%), and 388/1446 (27%) were classified as unprovoked VTE. In 12/1446 (0.8%), cancer was diagnosed synchronously with VTE on the initial imaging investigation. Additional screening imaging was performed in 232/388 (60%) including abdominopelvic CT in 205 (53%) patients with unprovoked VTE. Only five additional cancers were identified, all of these occurring in patients with clinical symptoms suspicious for cancer. None of the additional CT examinations identified any clinically occult cancer in asymptomatic patients, and subsequent mean follow-up of 22 (SD=6) months also failed to reveal any further cancer diagnosis. CONCLUSION: Contrary to the National Institute of Health and Care Excellence (NICE) guidance, the yield of performing additional abdominopelvic CT as a screening tool for occult cancer in asymptomatic patients with unprovoked VTE is negligible. A more selective and clinically-driven assessment of these patients is recommended. PMID- 27005018 TI - Antigen-specific TIL therapy for melanoma: A flexible platform for personalized cancer immunotherapy. AB - Tumor infiltrating lymphocyte (TIL) therapy has shown objective clinical response rates of 50% in stage IV melanoma patients in a number of clinical trials. Nevertheless, the majority of patients progress either directly upon therapy or after an initial period of tumor control. Recent data have shown that most TIL products that are used for therapy contain only low frequencies of T cells reactive against known melanoma-associated epitopes. Because of this, the development of a technology to create T-cell products that are enriched for reactivity against defined melanoma-associated antigens would seem valuable, both to evaluate the tumoricidal potential of T cells directed against different antigen classes and to potentially increase response rates. Here, we developed and validated a conditional MHC streptamer-based platform for the creation of TIL products with defined antigen reactivities. We have used this platform to successfully enrich both high-frequency (>=1%) and low-frequency (<1%) tumor specific CD8(+) T-cell populations, and thereby created T-cell products with enhanced tumor recognition potential. Collectively, these data demonstrate that selection of antigen-specific T-cell populations can be used to create defined T cell products for clinical use. This strategy thus forms a highly flexible platform for the development of antigen-specific cell products for personalized cancer immunotherapy. PMID- 27005019 TI - Response of enzyme activities and microbial communities to soil amendment with sugar alcohols. AB - Changes in microbial community structure are widely known to occur after soil amendment with low-molecular-weight organic compounds; however, there is little information on concurrent changes in soil microbial functional diversity and enzyme activities, especially following sorbitol and mannitol amendment. Soil microbial functional diversity and enzyme activities can be impacted by sorbitol and mannitol, which in turn can alter soil fertility and quality. The objective of this study was to investigate the effects of sorbitol and mannitol addition on microbial functional diversity and enzyme activities. The results demonstrated that sorbitol and mannitol addition altered the soil microbial community structure and improved enzyme activities. Specifically, the addition of sorbitol enhanced the community-level physiological profile (CLPP) compared with the control, whereas the CLPP was significantly inhibited by the addition of mannitol. The results of a varimax rotated component matrix demonstrated that carbohydrates, polymers, and carboxylic acids affected the soil microbial functional structure. Additionally, we found that enzyme activities were affected by both the concentration and type of inputs. In the presence of high concentrations of sorbitol, the urease, catalase, alkaline phosphatase, beta glucosidase, and N-acetyl-beta-d-glucosaminidase activities were significantly increased, while invertase activity was decreased. Similarly, this increase in invertase, catalase, and alkaline phosphatase and N-acetyl-beta-d-glucosaminidase activities was especially evident after mannitol addition, and urease activity was only slightly affected. In contrast, beta-glucosidase activity was suppressed at the highest concentration. These results indicate that microbial community diversity and enzyme activities are significantly affected by soil amendment with sorbitol and mannitol. PMID- 27005020 TI - An intravaginal ring for sustained and simultaneous delivery of 4 drugs. PMID- 27005021 TI - Long-term release of water-soluble drugs using microsol-electrospun nanofiber sheets. PMID- 27005022 TI - Nanoparticles targeting to osteoblasts for potential intracellular pathogen elimination. PMID- 27005023 TI - Delivery of polyamine-functionalized mesoporous silica nanoparticles into cancerous cells. PMID- 27005024 TI - TGF-beta3 encapsulated PLCL scaffold by supercritical CO2-HFIP co-solvent system for cartilage tissue engineering. PMID- 27005025 TI - The stability of silk fibroin nanoparticles coated with cationic polymers in biological media. PMID- 27005026 TI - Infrared radiation triggered detachable bio-adhesive hybrid hydrogels. PMID- 27005027 TI - Therapeutic response to HMGB1-R3V6-conjugated Ym1/Ym2 siRNA complex in ovalbumin induced murine asthma. PMID- 27005029 TI - Preparation of fluorescent microspheres via layer-by-layer self-assembly. PMID- 27005028 TI - Oral prodrug strategy for poorly soluble drugs. PMID- 27005030 TI - pH-sensitive OEI-poly(aspartic acid-b-lysine) as charge shielding system for gene delivery. PMID- 27005031 TI - A tumor-targeting MRI contrast agent based on hypoxia and pH-responsive nanogel. PMID- 27005032 TI - Uniform-sized PLGA-HSPC lipospheres as a biocompatible platform for controlled release of proteins and peptides. PMID- 27005033 TI - Glyoxalated chitosan-5-fluorouracil/chitosan-folate as colon-specific and colon cancer cell-targeted device. PMID- 27005034 TI - Sequence-defined nucleic acid carriers combining distinct modules for complexation, shielding, receptor-targeting and endosomal escape. PMID- 27005036 TI - Synthesis of PLGA-gemcitabine conjugate and its anti-proliferative properties. PMID- 27005035 TI - Polymer inhibitors of ABC transporter overcoming multidrug resistance: Synthesis, characterization and in vitro evaluation. PMID- 27005037 TI - Tumor-pH activated charge-conversional and reducible poly(vinyl alcohol) nanogels for enhanced cell uptake and intracellular DOX release. PMID- 27005038 TI - A drug delivery system based on novel hollow mesoporous silica nanospheres. PMID- 27005039 TI - Anti-tumor effects in mice induced by Bcl-2 targeted siRNA delivered by TAT-g-CS vector. PMID- 27005040 TI - W/O nanoemulsion-based intranasal drug delivery system of Panax notoginseng saponins for brain targeting. PMID- 27005041 TI - Rapid detection of rare-event cell by SUPER Dots based diagnostics nano-platform. PMID- 27005042 TI - Preparation and functional characterization of tumor-targeted folic acid-chitosan conjugate nanoparticles loaded with mitoxantrone. PMID- 27005043 TI - The fabrication of glucose-sensitive insulin carriers with layer-by-layer assembly technique. PMID- 27005044 TI - pH-sensitive nanocarriers for enhanced tumor retention and rapid intracellular drug release. PMID- 27005045 TI - Oral delivery of protein and anticancer drugs by uniform-sized chitosan micro/nanoparticles with autofluorescent property. PMID- 27005046 TI - Neural interfaces with electrically controllable delivery of manganese ions applied for MEMRI-functionalized deep brain stimulation. PMID- 27005047 TI - Two-way combination chemotherapy for synergistic tumor capture. PMID- 27005048 TI - Regulating the surface charges of polymeric microparticles to improve the efficacy of particle-adjuvanted vaccine. PMID- 27005049 TI - Anisamide-functionalized intelligent polymersomes mediate targeted delivery of methotrexate into lung cancer cells. PMID- 27005050 TI - A novel biomacromolecule controlled-release system based on mesoporous silica nanoparticles with large pore size and small particle size. PMID- 27005051 TI - IgY-loaded calcium phosphate nanospheres: Preparation, sustained release and antibacterial activity. PMID- 27005052 TI - Construction of reverse vesicles based on cyclodextrin-cholesterol inclusion complexation. PMID- 27005053 TI - Preparation of PEGylated chelator-stabilized calcium phosphate nanoparticles for liver-targeted delivery of nucleic acid. PMID- 27005054 TI - Novel nano-spray-dried powders for efficient pulmonary drug delivery. PMID- 27005055 TI - Enhanced therapeutic efficacy with hydrophobic polyphosphoester-based nanoparticles via improved intracellular drug release. PMID- 27005056 TI - The effect of curcumin delivery using peptide micelles to pancreatic beta cells under the hypoxia condition. PMID- 27005057 TI - Rg3-loaded biodegradable composite electrospun fibers for long-term inhibition of hypertrophic scarring. PMID- 27005058 TI - Redox responsive diselenide colloidosomes templated from Pickering emulsions for drug release. PMID- 27005059 TI - Docetaxel-loaded nanoparticles of dendrimer-like amphiphilic copolymer for cancer therapy. PMID- 27005060 TI - Multifunctional three-dimensional scaffolds for treatment of spinal cord injury. PMID- 27005062 TI - A novel brush-shaped copolymer for drug delivery. PMID- 27005061 TI - Synthesis of acid-degradable hyperbranched poly(resveratrol-co-ketal)-b-mPEG nanoparticles. PMID- 27005063 TI - Comb-like polycysteine with different side groups: Synthesis and multi-responsive nanostructure. PMID- 27005064 TI - Smart lipid capped mesoporous silica nanoparticles with tumor extracellular pH activated charge-conversion property for deep hepatocellular carcinoma penetration. PMID- 27005065 TI - Glucose-responsive micelles for insulin release. PMID- 27005066 TI - Triggered release of anticancer drugs from PEGylated polydopamine nanospheres by near-infrared light. PMID- 27005067 TI - A modular approach toward multifunctional supramolecular nanopolyplexes for targeting gene delivery. PMID- 27005069 TI - A microemulsion-based delivery system for enhanced absorption of epimedium flavonoids by real-time enzymolysis and mucoadhesive strategy. PMID- 27005068 TI - REDV-linked biodegradable polymeric micelles as the transfer vector of ZNF580 for the proliferation of endothelial cells. PMID- 27005070 TI - Amphiphilic block copolymer of SN38 prodrugs by atom transfer radical polymerization: Synthesis, kinetic studies and self-assembly. PMID- 27005071 TI - Zwitterionic poly(carboxybetaine) modified liposomes enhancing tumor therapy without accelerated blood clearance phenomenon. PMID- 27005072 TI - Targeted hepatoma chemotherapy in vivo using galactose-decorated crosslinked pH sensitive degradable micelles. PMID- 27005073 TI - Doxorubicin prodrug thermogel as sustained drug reservoir for in situ malignant therapy. PMID- 27005074 TI - Long circulating and stable polymeric micelles for targeted delivery of paclitaxel. PMID- 27005075 TI - Nanocomposite porous scaffolds for bone tissue engineering by emulsion templating. PMID- 27005076 TI - Lipid-polymer hybrid nanoparticles for the delivery of gemcitabine. PMID- 27005077 TI - Synergistic targeted delivery of payload into cancer cells using liposomes co modified with photolabile-caged cell-penetrating peptides and targeting ligands. PMID- 27005078 TI - Zwitterionic pendant polymer and doxorubicin decorated beta-cyclodextrin guest host micelles for efficient drug delivery. PMID- 27005079 TI - Co-delivery of doxorubicin and amphiphilic derivative of Gd-DTPA with lipid polymer hybrid nanoparticles for simultaneous imaging and targeted therapy of cancer. PMID- 27005080 TI - Novel microcapsules for drug and gene delivery. PMID- 27005082 TI - Phospholipid-like amphiphilic polymer conjugate micelles for on-demand intracellular curcumin delivery. PMID- 27005081 TI - Polymersomes of biodegradable polysarcosine-block-poly(epsilon-caprolactone). PMID- 27005083 TI - Synthesis and research on pH and redox dual responsive UV-cross-linked micelle. PMID- 27005084 TI - Preparation of fluorescent core/shell nanoparticles from amphiphilic cellulose based copolymers for tumor cell imaging. PMID- 27005085 TI - Co-delivery of poly I:C and STAT3 siRNA by nanovaccines effectively overcomes tumor-associated dendritic cell dysfunction and elicits anti-tumor immune response. PMID- 27005086 TI - Bioreducible cross-linked nanoshell enhances gene transfection of polycation/DNA polyplex in vivo. PMID- 27005087 TI - pH-Responsive supramolecular prodrug micelles based on cucurbit[8]uril for intracellular drug delivery. PMID- 27005088 TI - Combinatorial synthesis and high throughput screening of lipidoids for gene delivery. PMID- 27005089 TI - Self-programmed pH-sensitive polymeric prodrug micelle for synergistic cancer therapy. PMID- 27005090 TI - cRGD-Functionalized AuNR-cored PEG-PCL nanoparticles for efficacious glioma chemotherapy. PMID- 27005092 TI - Stimuli-responsive fluorescent supramolecular polymers based on pillarenes for controlled drug release. PMID- 27005091 TI - Immobilization of nucleic acid binding polymers as anti-inflammatory agent in autoimmunity. PMID- 27005093 TI - Nucleolin targeting AS1411 aptamer modified pH-sensitive micelles: A dual functional strategy for paclitaxel delivery. PMID- 27005094 TI - Co-delivery of doxorubicin and P-gp siRNA into human breast cancer cells by functionalized PLGA nanobubbles and ultrasound imaging in vitro. PMID- 27005096 TI - X-ray CT detection and photo ablation of metastatic positive lymph node with HER 2 targeting W18O49 platform. PMID- 27005095 TI - Targeted CT imaging of cancer cells using PEGylated low-generation dendrimer entrapped gold nanoparticles. PMID- 27005097 TI - Self-assembled, dual drug carrying polymer-drug conjugate for co-delivery. PMID- 27005098 TI - Self-assembled amphiphilic sequence-defined PEGylated three-arm oligo(ethanamino)amides via NCL reaction for drug delivery: Impact of building blocks on controlled release. PMID- 27005099 TI - Extracellular pH-sensitive mixed micelles for prostate tumor targeted anticancer drug delivery. PMID- 27005100 TI - Hyaluronic acid based injectable hydrogels for localized and sustained gene delivery. PMID- 27005101 TI - Reduction-sensitive injectable hyperbranched polyphosphoramidate-hyaluronan hybrid hydrogels for controlled protein release. PMID- 27005102 TI - QDs-PTX-silica hybrid nanocapsules for targeted cancer imaging and chemotherapy. PMID- 27005103 TI - Interface crosslinked poly(ethylene glycol)-poly(amino acid)s copolymer micelles for reduction-triggered release of doxorubicin. PMID- 27005104 TI - Color tuning of fluorescent microspheres with poly(p-phenylenevinylene) as the fluorophore. PMID- 27005105 TI - Effect of molecular adjuvant inclusion in pH-sensitive polymer-modified liposomes on their performance as antigen delivery carriers for cancer immunotherapy. PMID- 27005106 TI - Effects of water/polymer friction coefficient and polymer moduli on drug release from polyelectrolyte hydrogel carriers. PMID- 27005107 TI - Synthesis and properties of zwitterionic dendrimer as drug and imaging probe carrier. PMID- 27005108 TI - Co-administration of iRGD enhancing the anticancer efficacy of cisplatin-loaded polypeptide nanoparticles. PMID- 27005109 TI - pH-sensitive poly(peptide-co-beta-amino ester)s micelles for enhanced cancer therapy. PMID- 27005110 TI - Hydrophobic N-acetyl-l-leucine grafted polyethylenimine as an efficient carrier for DNAzyme delivery. PMID- 27005111 TI - Electrospun attapulgite-doped poly(lactic-co-glycolic acid) nanofibers for osteogenic differentiation of human mesenchymal stem cells. PMID- 27005112 TI - Gd2O3 nanocrystal-based autofluorescent composite nanoparticles as T1-weighted contrast agents. PMID- 27005113 TI - Mechanisms involved in electrospraying of macromolecules for micro-delivery. PMID- 27005114 TI - Novel redox-sensitive mixed micelle with enhanced antitumor activity. PMID- 27005115 TI - pH-responsive PEGylated doxorubicin for efficient cancer chemotherapy. PMID- 27005116 TI - Electrospun PLA/MWCNT composite nanofibers for combined chemo- and photothermal therapy with near-infrared radiation. PMID- 27005117 TI - Sequential intra-intercellular nanoparticle delivery system for localized delivery of doxorubicin. PMID- 27005118 TI - beta-cyclodextrin based colon targeted delivery systems of aspirin: Synthesis, and in vitro assessment. PMID- 27005119 TI - Stabilization of layered double hydroxide nanoparticles by bovine serum albumin pre-coating for drug/gene delivery. PMID- 27005120 TI - Integrated therapy on residual tumor after palliative operation using dual-phase drug releasing electrospun fibrous scaffolds. PMID- 27005121 TI - Strongly fluorescent hydrogel with carbon dots embedded in matrices in situ. PMID- 27005122 TI - Lymphatic-targeted cationic liposomes: A robust vaccine adjuvant for promoting long-term immunological memory. PMID- 27005123 TI - Disulfide-based cationic polyurethanes for gene transfection in human primary cells. PMID- 27005124 TI - Design of pH-sensitive supramolecular assembly for cell targeting and controlled release. PMID- 27005125 TI - A directional liquid-transfer nonwoven for skin tissue engineering. PMID- 27005126 TI - PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for localized and combined treatment of human osteosarcoma. PMID- 27005127 TI - Glutathione-responsive C2-symmetric benzene-based co-assembly hydrogels. PMID- 27005128 TI - Synergistic effect of collagen-based glucophage-loaded biodegradable nanofibrous membranes with largely enhanced collagen content for accelerating diabetic wound repair. PMID- 27005129 TI - Synthesis and application of polyacrylic acid-based nanoparticles for photodynamic therapy. PMID- 27005130 TI - Thermo/pH dual responsive beta-cyclodextrin magnetic microspheres for anti-cancer drug controlled release. PMID- 27005131 TI - A near-infrared photothermal-responsive graphene-based nanohybrid for combination cancer therapy. PMID- 27005132 TI - PEG-based thermo-responsive poly (beta-thioether ester) for ROS-triggered drug delivery. PMID- 27005133 TI - Regulation of hydrophobicity of polyphosphoester based drug delivery system for enhanced cancer therapy. PMID- 27005134 TI - Targeting glucose uptake of glioma cells by siRNA delivery with polymer nanoparticle. PMID- 27005135 TI - A novel ultrasonic-triggered drug release and tracked drug delivery system based on gas-filled BSA microbubbles and gelatin nanogels. PMID- 27005136 TI - Poly(L-lysine)-based cylindrical copolypeptide brushes as potential drug and gene carriers. PMID- 27005137 TI - Wheat germ agglutinin nanocage stabilized drug nanocrystals cross intestinal epithelium barrier via goblet cells. PMID- 27005138 TI - Controlled cross-linking strategy for formation of hydrogels, microgels and nanogels. PMID- 27005139 TI - Synthesis of enzyme-induced supramolecular aggregates for measuring enzymatic activity by dual-wavelength photoacoustic imaging. PMID- 27005140 TI - Multi-functional microemulsion delivery system to overcome tumor multidrug resistance. PMID- 27005141 TI - Zwitterionic poly(lysine methacrylate) brush as an effective carrier for drug delivery. PMID- 27005142 TI - Glucose-sensitive nanogel for controlled release of insulin and its blood safety. PMID- 27005143 TI - Spatiotemporal delivery of small molecule therapeutics using a thermosensitive liposome loaded hydrogel. PMID- 27005144 TI - Smart hydrogel beads with potential therapeutic target in Caco-2 colon cancer cells. PMID- 27005145 TI - Polyelectrolyte complexes of poly[(2-dimethylamino) ethyl methacrylate]/chondroitin sulfate obtained at different pHs: Preparation, characterization, cytotoxicity and controlled release of chondroitin sulfate. PMID- 27005146 TI - Pullulan-modified spray-dried powders for pulmonary drug delivery. PMID- 27005147 TI - pH-sensitive polysaccharide derivatives-modified liposomes as antigen delivery vehicles for cancer immunotherapy. PMID- 27005148 TI - Encapsulation of doxorubicin within lactobionic acid-modified multifunctional poly(amidoamine) dendrimers for targeted therapy of liver cancer cells. PMID- 27005149 TI - Development of cationic block copolymers for gene delivery. PMID- 27005150 TI - Preparation and investigation of smart hydrogels of thiolated dextran and miR 145. PMID- 27005151 TI - Controlled cyclic drug release based on chemomechanical gels. PMID- 27005152 TI - Coordination micelles containing silver nanoparticles and the antibacterial activity thereof. PMID- 27005153 TI - pH and thermo dual-responsive polyaspartamide derivatives by click chemistry for drug delivery. PMID- 27005154 TI - Targeted delivery of doxorubicin by lactobionic acid-modified laponite to hepatocarcinoma cells. PMID- 27005155 TI - Polymer vesicles assembled from ALG-g-PNIPAM and beta-cyclodextrin through inclusion complexation for drug release. PMID- 27005156 TI - Controlled release of cell sheet by saccharide and temperature dual-responsive hydrogel layer. PMID- 27005157 TI - RGDC functionalized and hydroxycamptothecin-encapsulated magnetic nanohybrids for integrin alphaVbeta3-targeted drug delivery. PMID- 27005158 TI - Camptothecin-conjugated biodegradable prodrug micelles for theranostic near infrared fluorescent imaging and intracellular drug release. PMID- 27005159 TI - Degradable and tunable supramolecular polymer micelles for drug delivery. PMID- 27005160 TI - Superfine crimped nanofibers fabricated by bubbfil electrospinning. PMID- 27005161 TI - Borane-conjugated poly(ester-carbonate) amphiphilic block copolymers as potential agents for boron neutron capture therapy. PMID- 27005162 TI - Doxorubicin hydrochloride and curcumin loaded silk fibroin/hydroxypropylcellulose hydrogels for localized chemotherapy of cancer. PMID- 27005163 TI - VCAM-1-targeted silica nanoparticles doped with FITC and Fe3O4 for dual-mode cellular imaging of LPS-induced inflammatory endothelial cells. PMID- 27005164 TI - Promotion of fibroblasts growth and collagen secretion by CA-nAg/Gelatin-FGF electrospun nanofibers as antibacterial wound dressing materials. PMID- 27005165 TI - Polyethylenimines modified by amino acids with different charge states and hydrophilic/hydrophobic properties for gene carriers. PMID- 27005167 TI - Self-assembled fluorodendrimers allow efficient transfection with ultra-low DNA dose. PMID- 27005166 TI - Biocompatible smectic polymer nanostructures with controlled morphologies and reduction-responsive properties. PMID- 27005168 TI - Semiconducting polymer dots with phosphorescent Ir(III)-complex for photodynamic cancer therapy. PMID- 27005169 TI - Development of a novel elastic and macroporous chitosan hydrogel for wound healing application. PMID- 27005170 TI - Hyperbranched polyglycidol/phosphatidylcholine and phosphatidylethanolamine hybrid liposomes for the pH-sensitive delivery of doxorubicin. PMID- 27005171 TI - Folate conjugated PEG-chitosan/graphene oxide nanocomplexes as potential carriers for pH-triggered drug release. PMID- 27005172 TI - A new metastable form of glycolide obtained via large scale high pressure experiments. PMID- 27005173 TI - Phosphatidylethanolamine polyglycidol bioconjugates for controlled drug delivery. PMID- 27005174 TI - Environmental pH-sensitive polymeric nano-carriers for targeted tumor delivery. PMID- 27005175 TI - Bacteria-responsive anti-infectious surfaces for tissue engineering and biomedical devices. PMID- 27005176 TI - Development of biodegradable electrospun nanofibers containing 17-AAG. PMID- 27005177 TI - Enhanced solubility, stability, and antitumor activity of the VESylated gemcitabine prodrug by co-assembly with TPGS. PMID- 27005178 TI - Cisplatin complexes stabilized poly(glutamic acid) for controlled delivery of doxorubicin. PMID- 27005179 TI - A dual-targeting strategy to enhance photodynamic efficacy using a pH-responsive polymeric micelles. PMID- 27005180 TI - A traceable porous bowl-like PLA@C-dots composite for in vitro drug delivery system: A case study of artemisinin. PMID- 27005181 TI - R8-modified polysarcosine-b-polylysine polypeptide to enhance circulation stability and gene delivery efficiency. PMID- 27005182 TI - A polyethylenimine derivative-based nanocarrier for the highly efficient delivery of p53 gene to inhibit the proliferation of cancer cells. PMID- 27005183 TI - Novel hydrogel adjuvant based on quaternized chitosan for H5N1 split vaccine. PMID- 27005184 TI - Synthesis of polymerized calcium silicate hydrate nanostructures as drug carriers. PMID- 27005185 TI - Two-phase microfluidic droplet flows of self-crosslinking polymer for the synthesis of protein delivery agent. PMID- 27005186 TI - Electrospun nanofibers of hydroxyapatite/collagen/chitosan promote osteogenic differentiation of the induced pluripotent stem cell-derived mesenchymal stem cells. PMID- 27005187 TI - Dendrimer complexed hydrogel for local delivery of PTX to inhibit recurrence of breast cancer. PMID- 27005188 TI - Heparosan based nanocarrier for rapid intracellular drug delivery. PMID- 27005189 TI - Biomimetic polymers responsive to a biological signaling molecule: Nitric oxide (NO) triggered reversible self-assembly of single macromolecular chains into nanoparticles. PMID- 27005190 TI - pH-sensitive polyion complex micelles for tunable intracellular drug delivery. PMID- 27005191 TI - Novel reversibly crosslinked chimaeric polypeptide polymersomes for active loading and intracellular release of doxorubicin hydrochloride. PMID- 27005192 TI - Er:YAG fractional laser as a percutaneous absorption promoter for controlled delivery of antibody in vitro. PMID- 27005193 TI - Combinational delivery of HMGB1 A box and heparin for acute lung injury. PMID- 27005194 TI - Design and synthesis of FRET-trackable HPMA-based biodegradable conjugates for drug/gene delivery. PMID- 27005196 TI - Cell specific doxorubicin delivery through the temperature responsive lipopolymer nanocarriers engineered by the combination of RAFT polymerization and click chemistry. PMID- 27005195 TI - Cell-transfecting multilayered surfaces from poly(amido amine)s. PMID- 27005197 TI - Effects of protein transduction domain combination for intracellular recombinant protein delivery. PMID- 27005198 TI - PEI modified biodegradable complex micelles as gene transfer vector for proliferation of ECs. PMID- 27005199 TI - Electrospun macroporous fibrous scaffolds. PMID- 27005200 TI - Pressure-crystallized carbon nanotube-core/polymer-sheath nanocables for drug delivery. PMID- 27005201 TI - Hollow hydroxyapatite@nano-Au@polyelectrolyte hybrid microparticles for triple responsive drug delivery. PMID- 27005202 TI - Preparation of antibacterial silver nanoparticle-coated PLLA grafted hydroxyapatite/PLLA composite electrospun fiber. PMID- 27005203 TI - Deoxycholic acid-polymer conjugates for gene delivery to ischemic stroke. PMID- 27005204 TI - Cellular uptake enhancement and internalization pathway determination for intracellular polymeric particles. PMID- 27005205 TI - In-situ forming glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering. PMID- 27005206 TI - Novel intra-alveolar drug carrier as a functional dressing for the alveolar osteitis treatment. PMID- 27005207 TI - Lung-targeted thermosensitive double-hydrophilic block glycopolymer micelles by RAFT polymerization. PMID- 27005208 TI - Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity. PMID- 27005209 TI - c(RGDfC)-decorated micelle as nanocarrier for targeting therapeutic of colon cancer. PMID- 27005210 TI - Doxorubicin-conjugated magnetic iron oxide nanoparticles for pH-sensitive and magnetic responsive drug delivery. PMID- 27005211 TI - Synergetic effect observed during development of drug-eluting biodegradable microspheres for transarterial chemoembolization (TACE) of solid tumors. PMID- 27005213 TI - Phenylboronic acid-functionalized polypeptide nanogel for glucose-responsive insulin release under physiological pH. PMID- 27005212 TI - Efficient antisense oligonucleotide delivery via non-covalent complexes of folic acid and modified polyethylenimine. PMID- 27005214 TI - Thermo-and pH dual-responsive mesoporous silica nanoparticles for controlled drug release. PMID- 27005215 TI - Traceless pH sensitive coating of polyplexes prepared from well-defined polycations. PMID- 27005216 TI - Core-shell supramolecular gelatin nanoparticles for "on demand" antibiotic delivery. PMID- 27005218 TI - Galactose and near infrared fluorescence probe conjugated pH-responsive copolymer for imaging of drug delivery. PMID- 27005217 TI - Block copolymer nanoparticles as light-induced hydrogen sulfide (H2S) donors. PMID- 27005219 TI - Anionic long circulating liposomes for hepatic targeted delivery of cisplatin. PMID- 27005220 TI - Hyaluronic acid derivative-modified liposomes as pH-sensitive anticancer drug delivery system. PMID- 27005221 TI - Triblock terpolymer/gold nanoparticle hybrid micelles with tunable morphology and nanoparticle location. PMID- 27005223 TI - Precisely regulated nanoarchitecture comprised of gold nanotemplate and unimer polyion complex for systemic delivery of siRNA. PMID- 27005222 TI - A thermosensitive glycol chitin hydrogel for the vaginal delivery of progesterone. PMID- 27005224 TI - Glycyrrhetinic acid-decorated and reduction-sensitive micelles for targeted cancer therapy. PMID- 27005225 TI - pH-triggered drug carrier for targeted co-delivery of genes and drugs. PMID- 27005226 TI - Fabrication of DOX and CPT dual-drug loaded PLGA nanofibrous mats for cancer treatment. PMID- 27005227 TI - Enhanced transdermal lymphatic drug delivery of hyaluronic acid modified transfersome for tumor metastasis therapy. PMID- 27005228 TI - Nanoclusters of superparamagnetic iron oxide nanoparticles coated with poly(dopamine) for magnetic field-directed, ultrasensitive MRI-guided photothermal cancer therapy. PMID- 27005229 TI - Catechol-grafted dendrimer with a neutral shell allows pH-triggered "off-on" release of bortezomib. PMID- 27005230 TI - In vitro inhibition of cancer stem cells by biguanidine-based macromolecular drug. PMID- 27005231 TI - Nanobody-functionalized polymersomes. PMID- 27005232 TI - Antibacterial ciprofloxacin hydrochloride incorporated PVA/regenerated silk fibroin nanofibers composite for wound dressing applications. PMID- 27005233 TI - Drug release mechanisms of chemically cross-linked albumin microparticles: Effect of the matrix erosion. PMID- 27005235 TI - Self-aggregates of hyperbranched epoxidized 2-hydroxyethyl methacrylate conjugates of methotrexate: Synthesis and in vitro drug delivery. PMID- 27005234 TI - Synthesis of hyperbranched polyglycidol-b-poly(N-isopropylacrylamide) using nitroxide-mediated polymerization for thermo-sensitive drug delivery system. PMID- 27005236 TI - Controlled-release of metronidazole from proline-based polymers prepared by RAFT polymerization: Molecular weight-dependence. PMID- 27005237 TI - Targeting exosomal miRNA with pH-sensitive liposome coated chitosan-siRNA nanoparticles for inhibition of hepatocellular carcinoma metastasis. PMID- 27005238 TI - Improving gene transfection efficacy of low generation dendrimers through specific hydrogen-bond recognition. PMID- 27005239 TI - Paclitaxel improved gene transfection efficiency through cell synchronization in SW480 cells. PMID- 27005240 TI - Modeling of caffeine release from a cellulosic substrate coated with microfibrillated cellulose. PMID- 27005242 TI - Design and synthesis of amphiphilic core-shell nanoparticles with temperature sensitive-shell for controllable intracellular uptake. PMID- 27005241 TI - Hybrid lipid-mesoporous silica for stimuli-responsive drug release and overcoming multidrug resistance. PMID- 27005243 TI - Poly(N-isopropylacrylamide)-based nanogels encapsulating gold nanoparticles for DNA delivery. PMID- 27005244 TI - Folate-conjugated biodegradable core cross-linked polyphosphoester micelles for targeted and pH-triggered drug delivery. PMID- 27005245 TI - Preparation and properties of novel microporous hydrogels with poly(ethylene glycol) dimethacrylate and carboxylated carbon nanotubes. PMID- 27005246 TI - Chimaeric polymersomes based on poly(ethylene glycol)-b-poly(l-leucine)-b-poly(l glutamic acid) for efficient delivery of doxorubicin hydrochloride into drug resistant cancer cells. PMID- 27005247 TI - Block copolymer hybrid calcium phosphate micelles for cancer diagnosis and neutron capture therapy. PMID- 27005248 TI - Doxorubicin-loaded pH-sensitive dextran-retinal nanoparticles suppress tumor growth by inducing both apoptosis and cell senescence. PMID- 27005249 TI - Near-infrared dye bound human serum albumin with separated imaging and therapy wavelength channels for imaging-guided photothermal therapy preventing tumor metastasis. PMID- 27005250 TI - PEI-g-P(LA-co-MMD)-g-PEI nanoparticles as gene carriers to promote the proliferation of human vascular endothelial cells. PMID- 27005251 TI - Cell laden and patterned chitosan microgel for micro-scale tissue engineering. PMID- 27005252 TI - Light and pH dual responsive polyion complex micelles for efficient protein delivery. PMID- 27005253 TI - A pH sensitive carboxymethyl cellulose-g-poly (acrylic acid)/polyvinylpyrrolidone/sodium alginate composite hydrogel bead for the controlled release of diclofenac. PMID- 27005254 TI - Doxorubicin-loaded polymeric micelles based on bioactive polypeptides: Suppress invasion of melanoma cells and alleviate doxorubicin-induced cardiotoxicity. PMID- 27005255 TI - Hydroxyapatite and vancomycin composited electrospun polylactide mat for osteomyelitis and bone defect treatment. PMID- 27005256 TI - Preparation of cationic lipid layered PLGA hybrid nanoparticles for gene delivery. PMID- 27005257 TI - Biodegradable poly(ethylene glycol) methyl ether acrylate-b-poly(l-lysine)-b poly(l-histidine) triblock copolypeptides for non-viral gene delivery. PMID- 27005258 TI - Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells. PMID- 27005259 TI - Preparation and controllable release behavior of edible zein hybrid nanoparticles. PMID- 27005260 TI - Chemically conjugating poly(amidoamine) with chondroitin sulfate to promote CD44 mediated endocytosis for miR-34a delivery. PMID- 27005261 TI - An advanced liver targeting RNAi based therapeutic system using tripodal RNA polymer nanoparticles. PMID- 27005262 TI - Dextran-platinum(IV) conjugate as drug carrier for triggered drug release. PMID- 27005263 TI - Promoting endothelial recovery and reducing neointimal hyperplasia using sequential release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents. PMID- 27005264 TI - Synthesis and release characteristics of ketoprofen conjugated with PEG-graft cyclodextrin. PMID- 27005265 TI - Studies on the synthesis, characterization and self-assembly of biocompatible amphiphilic copolymers of poly[2-(methacryloyloxy)ethylphosphorylcholine] modified poly(epsilon-caprolactone). PMID- 27005266 TI - A theoretical hypothesis on co-precipitation of hydrophobic antitumor drug and amphiphilic block copolymers. PMID- 27005267 TI - PEG-polypeptide conjugated with LHRH as an efficient vehicle for targeted delivery of doxorubicin to breast cancer. PMID- 27005268 TI - pH and reduction-sensitive disulfide cross-linked polyurethane micelles for bio triggered anti-tumor drug delivery. PMID- 27005269 TI - The LC-MS method for the simultaneous analysis of selected fat-soluble vitamins and their metabolites in serum samples obtained from pediatric patients with cystic fibrosis. AB - Cystic fibrosis (CF) is one of the most common genetic diseases in children and affects mainly respiratory and digestive system functions. Despite the prolonged supplementation of vitamins, malnutrition manifested by poor growth and weight loss in children is a major complication in CF related to pancreatic insufficiency and difficulty in absorbing fat-soluble vitamins. In the present study, we have developed and validated a sensitive and accurate high-performance liquid chromatography coupled to mass spectrometry (LC-MS) method for the simultaneous quantification of three fat-soluble vitamins (A, E and K1) and two vitamin D3 active metabolites: 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in serum samples obtained from pediatric patients with CF. In optimized conditions, the LC-MS method was highly sensitive and presented excellent linearity with a regression coefficient higher than 0.999. The accuracy was in the range of 87.55-95.58 % for all analytes. The precision of the method, expressed as% RSD, ranged from 1.36 % to 3.74 % as the intra-day variability and from 2.35 % to 7.98 % as the inter-day precision for all the studied compounds. Sample preparation included a protein precipitation step with the use of methanol followed by liquid-liquid extraction with n-hexane. The statistical analysis (t test and principal component analysis (PCA)) of the obtained results revealed significant changes in the plasma level of the analyzed compounds, with 25 hydroxyvitamin D3, vitamin E and K1 present at extremely low concentrations in patients with cystic fibrosis in comparison to healthy controls. The elaborated method reached the expectations for the fast and reliable assessment of fat soluble vitamin status in children with cystic fibrosis in order to diagnose the disease and monitor the treatment process. PMID- 27005270 TI - Structural studies on the mechanism of protein aggregation in age related neurodegenerative diseases. AB - The progression of many neurodegenerative diseases is assumed to be caused by misfolding of specific characteristic diseases related proteins, resulting in aggregation and fibril formation of these proteins. Protein misfolding associated age related diseases, although different in disease manifestations, share striking similarities. In all cases, one disease protein aggregates and loses its function or additionally shows a toxic gain of function. However, the clear link between these individual amyloid-like protein aggregates and cellular toxicity is often still uncertain. The similar features of protein misfolding and aggregation in this group of proteins, all involved in age related neurodegenerative diseases, results in high interest in characterization of their structural properties. We review here recent findings on structural properties of some age related disease proteins, in the context of their biological importance in disease. PMID- 27005272 TI - Clinical case discussion: using a reflecting team. PMID- 27005271 TI - Diagnostics for pulmonary tuberculosis. AB - Tuberculosis (TB) remains a leading cause of human suffering and mortality despite decades of effective treatment being available. Accurate and timely diagnosis remains an unmet goal. The HIV epidemic has also led to new challenges in the diagnosis of TB. Several new developments in TB diagnostics have the potential to positively influence the global campaign against TB. We aim to review the performance of both established as well as new diagnostics for pulmonary TB in adults, and discuss the ongoing challenges. PMID- 27005273 TI - Predictors of spermatogenesis in radical orchiectomy specimen and potential implications for patients with testicular cancer. AB - OBJECTIVE: To assess the ability of semen analysis and other patients' characteristics to predict the presence of spermatozoa in radical orchiectomy pathological specimen, and describe potential implications for patients with azoospermia and testis cancer. DESIGN: Retrospective cohort study. SETTING: Tertiary hospital. PATIENT(S): A total of 214 consecutive patients with testicular cancer who underwent radical orchiectomy between 1997 and 2015. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory, and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with the presence of spermatozoa in the noninvolved ipsilateral testicular parenchyma. RESULT(S): Spermatozoa were found in the pathological specimen of 145 patients (67.8%). At multivariate analysis, increased tumor size was the only factor associated with lower rates of spermatozoa in the specimen. Mean tumor diameter was 4.06 cm, and spermatozoa were found in 83% and 49% of testes with tumor diameters <4 and >=4 cm, respectively. Preoperative semen analysis records were available for 107 patients. Oligozoospermia, severe oligozoospermia, azoospermia, and cryptozoospermia were observed in 17 (16%), 18 (17%), 9 (8%) and 3 (3%) patients, respectively. Sperm concentration and motility were not associated with complete spermatogenesis. Seven of 12 patients (58%) with either azoospermia or cryptozoospermia had mature sperm in their pathological sections. CONCLUSION(S): Larger testicular cancers are associated with lower rates of spermatozoa in the ipsilateral testis. Given the substantial likelihood (~60%) of spermatozoa to be present in the cancerous testis of patients with azoospermia and cryptozoospermia, concomitant oncologic testicular sperm extraction (TESE) can be considered in these selected patients. PMID- 27005274 TI - Obstetric and neonatal outcomes in blastocyst-stage biopsy with frozen embryo transfer and cleavage-stage biopsy with fresh embryo transfer after preimplantation genetic diagnosis/screening. AB - OBJECTIVE: To study whether embryo biopsy for preimplantation genetic diagnosis/preimplantation genetic screening (PGD/PGS) can influence pregnancy complications and neonatal outcomes. DESIGN: Retrospective analysis. SETTING: University-affiliated center. PATIENT(S): This study included data from women and their neonates born after PGD/PGS (n = 317). MAIN OUTCOME MEASURE(S): Questionnaires were designed to obtain information relating to pregnancy complications and neonatal outcomes. INTERVENTION(S): Two major strategies for PGD/PGS were evaluated. Blastocyst-stage biopsy and frozen embryo transfer (BB FET) was carried out in 166 patients, and cleavage-stage biopsy and fresh embryo transfer (CB-ET) was carried out in 129 patients. RESULT(S): The incidence of gestational hypertension was significantly higher in BB-FET compared with in CB ET (9.0% vs. 2.3%, adjusted odds ratio [OR] and 95% confidence interval [CI], 4.85 [1.34, 17.56]). In twins, the birthweight (median [range], 2.70 kg [1.55 3.60 kg] vs. 2.50 kg [1.23-3.75 kg]) was higher in BB-FET than in CB-ET and the gestational age was longer in BB-FET than in CB-ET (median [range], 36.71 weeks [31.14-39.29 weeks] vs. 35.57 weeks [30.57-38.43 weeks]). There was no difference in the incidence of singleton births between the two groups except in the incidence of preterm births (28-37 weeks; 5.3% vs. 16.5% in CB-ET and BB-FET). No significant differences were detected in the incidence of perinatal deaths, birth defects, gender of neonates, and large for gestational age in both singletons and twins, although the numbers of some events were small. CONCLUSION(S): BB-FET is associated with a higher incidence of gestational hypertension but better neonatal outcomes compared with CB-ET, especially in twins. PMID- 27005275 TI - The role of neutrophils in immune dysfunction during severe inflammation. AB - Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis. PMID- 27005276 TI - Spatial distribution and temporal trends of farmland soil PBDEs: processes and crop rotation effects. AB - The concentration and temporal trend of PBDEs in farmland soil during a circle of crop rotation period within an e-waste dismantling area of South China were investigated. The averaged current concentration of total PBDEs in the farmland soil was averaged 19.1 +/- 20.7 ng/g dry weight, which was much lower than the PBDE level in roadside soil and in topsoil near e-waste dismantling sites. Spatial distribution of total PBDEs concentration in the study area showed higher level at the field near e-waste workshops and lower at the distanced farmland area. Soil organic carbon content was significantly correlated with concentration of BDE209 (r = 0.704, p < 0.01), but not related with the sum concentration of other PBDE compounds (r = 0.097, p > 0.1). During the whole crop rotation circle, the temporal concentration of PBDEs in the farmland soil was highest (25.3 +/- 11.4 ng/g dry wt.) in April when early paddy had been transplanted for 1 or 2 weeks. When the crop rotated to autumn peanut in August and the land is turning dry, the PBDEs concentration in farmland soil reached the lowest level which was 8.1 +/- 1.2 ng/g dry wt. The temporal trend of PBDEs in farmland soil was not consistent with that of atmospheric PBDEs and soil total organic carbon (TOC) content during the rotation cycle. It was concluded that the dynamics of PBDEs in the farmland soil is influenced by multiple, interacting factors, and not clearly related to neither the atmospheric deposition nor the organic carbon content of the soil, but possibly related to the micro-environmental conditions changed by crop rotation process. PMID- 27005277 TI - New process for copper migration by bioelectricity generation in soil microbial fuel cells. AB - The soil microbial fuel cell (MFC) is a promising biotechnology for the bioelectricity recovery as well as the remediation soil. Moreover, there were no studies on the heavy metal pollution in a soil MFC yet. A soil MFC was constructed to remediate the contaminated soil, and the electric field was generated from the oxidation of the acetate at the anode. We demonstrated the copper migration, the power generation, and the pH variation in the soil and the electrodes. The maximal voltage and the power density of 539 mV and 65.77 m W/m(2) were obtained in the soil MFC. The chemical fractionation of copper (Cu) was analyzed with a modified BCR sequential extraction method. The soluble Cu form and the total Cu contents from the anode to the cathode increased, and the difference between them kept growing over time. The Cu fractions in the soil and the electrodes were converted with the change of the dramatic pH from the anode to the cathode. There was a focusing effect leading to the change of the Cu forms, and the extractable acid form content increased in the three fifths where the acid and the alkali fronts met. PMID- 27005278 TI - Contribution of inorganic and organic components to sorption of neutral and ionizable pharmaceuticals by sediment/soil. AB - Our previous study showed that the sorption coefficient of certain polar pharmaceuticals to river sediment, especially particular amines, was unexpectedly high. Thus, we conducted sorption experiments of selected polar pharmaceuticals and pyrene derivatives, including amines, carboxylic acids, and neutral compounds, to model clay minerals, i.e., montmorillonite and kaolin, in addition to silica sands and humic substances. The contribution of each component was roughly estimated by simple fractionation of the individual sorption coefficients. Relatively high sorption coefficients (K d values) were found, especially for amines on clay minerals, which suggest that electrochemical affinity may play an important role. The estimated contribution percentage suggests a relatively large contribution from inorganic constituents, such as clay minerals, for silt loam soil; in contrast, organic components predominantly contribute for sandy river sediments. These findings could be the key to understanding not only the fate and transport but also bioavailability and environmental risks of pharmaceuticals, which are mostly polar and/or ionizable. PMID- 27005279 TI - Factorial design application in photocatalytic wastewater degradation from TNT industry-red water. AB - In trinitrotoluene (TNT) purification process, realized in industries, there are two washes carried out at the end of the procedure. The first is performed with vaporized water, from which the first effluent, called yellow water, is originated. Then, a second wash is performed using sodium sulfite, generating the red water effluent. The objective of this work was to get the best conditions for photocatalytic degradation of the second effluent, red water, in order to reduce toxicity and adjust legal parameters according to regulatory agencies for dumping these effluents into waterways. It has used a statistical evaluation for factor interaction (pH, concentration) that affects heterogeneous photocatalysis with titanium dioxide (TiO2). Thus, the treatment applied in the factorial experimental design consisted of using a volume equal to 500 mL of the effluent to 0.1 % by batch treatment, which has changed TiO2 pH and concentration, according to the design, with 20 min time for evaluation, where it was used as response to the reduction of UV-Vis absorption. According to the design responses, it has obtained optimum values for the parameters evaluated: pH = 6.5 and concentration of 100 mg/L of TiO2 were shown to be efficient when applied to red water effluent, obtaining approximately 91 % of discoloration. PMID- 27005280 TI - Toward the sustainability of health interventions implemented in sub-Saharan Africa: a systematic review and conceptual framework. AB - BACKGROUND: Sub-Saharan Africa (SSA) is facing a double burden of disease with a rising prevalence of non-communicable diseases (NCDs) while the burden of communicable diseases (CDs) remains high. Despite these challenges, there remains a significant need to understand how or under what conditions health interventions implemented in sub-Saharan Africa are sustained. The purpose of this study was to conduct a systematic review of empirical literature to explore how health interventions implemented in SSA are sustained. METHODS: We searched MEDLINE, Biological Abstracts, CINAHL, Embase, PsycInfo, SCIELO, Web of Science, and Google Scholar for available research investigating the sustainability of health interventions implemented in sub-Saharan Africa. We also used narrative synthesis to examine factors whether positive or negative that may influence the sustainability of health interventions in the region. RESULTS: The search identified 1819 citations, and following removal of duplicates and our inclusion/exclusion criteria, only 41 papers were eligible for inclusion in the review. Twenty-six countries were represented in this review, with Kenya and Nigeria having the most representation of available studies examining sustainability. Study dates ranged from 1996 to 2015. Of note, majority of these studies (30 %) were published in 2014. The most common framework utilized was the sustainability framework, which was discussed in four of the studies. Nineteen out of 41 studies (46 %) reported sustainability outcomes focused on communicable diseases, with HIV and AIDS represented in majority of the studies, followed by malaria. Only 21 out of 41 studies had clear definitions of sustainability. Community ownership and mobilization were recognized by many of the reviewed studies as crucial facilitators for intervention sustainability, both early on and after intervention implementation, while social and ecological conditions as well as societal upheavals were barriers that influenced the sustainment of interventions in sub-Saharan Africa. CONCLUSION: The sustainability of health interventions implemented in sub-Saharan Africa is inevitable given the double burden of diseases, health care worker shortage, weak health systems, and limited resources. We propose a conceptual framework that draws attention to sustainability as a core component of the overall life cycle of interventions implemented in the region. PMID- 27005281 TI - Lessons learned from a prolonged and costly norovirus outbreak at a Scottish medicine of the elderly hospital: case study. AB - BACKGROUND: Norovirus outbreaks are a major burden for healthcare facilities globally. AIM: Lessons learned to inform an action plan to improve facilities as well as responses to norovirus within the medicine of the elderly (MoE) hospital as well as other NHS (National Health Service) Lothian facilities. METHODS: This study investigated the impact of a prolonged outbreak at an MoE hospital in one of the 14 Scottish health boards between February and March 2013. FINDINGS: In all, 143 patients (14.80 cases per 1000 inpatient bed-days) and 30 healthcare staff (3.10 cases per 1000 inpatient bed-days) were affected clinically and 63 patients were confirmed virologically. Restricting new admissions to affected units resulted in 1192 lost bed-days. The cost due to lost bed-days in addition to staff absence and management of the outbreak was estimated at L341,534 for this incident alone. At certain points during the outbreak, the whole facility was closed with resulting major impact on the health board's acute care hospitals. CONCLUSION: Due to the outbreak, new measures were implemented for the first time within NHS Lothian that included floor-by-floor (instead of individual) ward closures, enhanced cleaning with chlorine-based products throughout the hospital, reduction in bed capacity with enhanced bed-spacing and interruption to direct admissions from the Board's general practice surgeries, and temporary suspension of visitors to affected areas. Together with regular communication to staff, patients, relatives, and the public throughout the outbreak and good engagement of staff groups in management of the incident, the outbreak was gradually brought under control. PMID- 27005282 TI - Laboratory diagnostics in dog-mediated rabies: an overview of performance and a proposed strategy for various settings. AB - The diagnosis of dog-mediated rabies in humans and animals has greatly benefited from technical advances in the laboratory setting. Approaches to diagnosis now include the detection of rabies virus (RABV), RABV RNA, or RABV antigens. These assays are important tools in the current efforts aimed at the global elimination of dog-mediated rabies. The assays available for use in laboratories are reviewed herein, as well as their strengths and weaknesses, which vary with the types of sample analyzed. Depending on the setting, however, the public health objectives and use of RABV diagnosis in the field will also vary. In non-endemic settings, the detection of all introduced or emergent animal or human cases justifies exhaustive testing. In dog RABV-endemic settings, such as rural areas of developing countries where most cases occur, the availability of or access to testing may be severely constrained. Thus, these issues are also discussed along with a proposed strategy to prioritize testing while access to rabies testing in the resource-poor, highly endemic setting is improved. As the epidemiological situation of rabies in a country evolves, the strategy should shift from that of an endemic setting to one more suitable for a decreased rabies incidence following the implementation of efficient control measures and when nearing the target of dog-mediated rabies elimination. PMID- 27005283 TI - Treatment of hepatitis delta virus genotype 3 infection with peg-interferon and entecavir. AB - OBJECTIVES: Hepatitis delta virus (HDV) is recognized as the most pathogenic and infectious among the hepatotropic viruses. Studies on the treatment of HDV have predominantly included European patients and carriers of genotype 1 (HDV-1) in their clinical protocols. For the Amazon region, data show that infected individuals have mainly Native American ancestry and that >90% of HDV carriers have the genotype 3 (HDV-3). Thus combined therapy clinical protocols do not adequately address the treatment of these patients. METHODS: A prospective, non randomized study was conducted in which 22 patients received 180MUg of pegylated interferon alpha 2a (PEG-IFN) plus entecavir at a dose of 0.5mg for 48 weeks, with a subsequent 24-week follow-up. Throughout treatment, the patients were monitored for biochemical responses and the kinetics of hepatitis B virus (HBV) and HDV viral loads. RESULTS: Of the 22 patients treated, 15 presented normal alanine aminotransferase values at the end of treatment (p=0.002). At week 24 of treatment, 86.4% of the patients did not present detectable HDV-RNA; at week 48, the rate of negative patients increased to >95% and remained the same after 6 months. With regard to HBV, only two patients (9%) still presented detectable HBV genetic material at the end of treatment, suggesting the effectiveness of combined therapy in combating the two viruses. CONCLUSIONS: These findings support the use of this effective therapeutic protocol for HDV-3 in patients of non-European ethnicity and suggest a possible 'easy to treat' variant when compared to HDV-1. PMID- 27005284 TI - Polysome Profiling Links Translational Control to the Radioresponse of Glioblastoma Stem-like Cells. AB - Changes in polysome-bound mRNA (translatome) are correlated closely with changes in the proteome in cells. Therefore, to better understand the processes mediating the response of glioblastoma to ionizing radiation (IR), we used polysome profiling to define the IR-induced translatomes of a set of human glioblastoma stem-like cell (GSC) lines. Although cell line specificity accounted for the largest proportion of genes within each translatome, there were also genes that were common to the GSC lines. In particular, analyses of the IR-induced common translatome identified components of the DNA damage response, consistent with a role for the translational control of gene expression in cellular radioresponse. Moreover, translatome analyses suggested that IR enhanced cap-dependent translation processes, an effect corroborated by the finding of increased eIF4F cap complex formation detected after irradiation in all GSC lines. Translatome analyses also predicted that Golgi function was affected by IR. Accordingly, Golgi dispersal was detected after irradiation of each of the GSC lines. In addition to the common responses seen, translatome analyses predicted cell line specific changes in mitochondria, as substantiated by changes in mitochondrial mass and DNA content. Together, these results suggest that analysis of radiation induced translatomes can provide new molecular insights concerning the radiation response of cancer cells. More specifically, they suggest that the translational control of gene expression may provide a source of molecular targets for glioblastoma radiosensitization. Cancer Res; 76(10); 3078-87. (c)2016 AACR. PMID- 27005285 TI - Trans-fascial closure in laparoscopic ventral hernia repair. AB - BACKGROUND: Laparoscopic incisional hernia repair has become widely accepted in the management of incisional hernias. There has been recent interest in combining fascial closure along with mesh placement to improve outcomes. We report our experience with this technique. METHODS: Cases were evaluated retrospectively from 2012 to 2015. There were no exclusions. Cases were included which involved laparoscopic ventral hernia repair with fascial closure and mesh placement. Fascial closure was performed using non-absorbable sutures passed with a suture passage device percutaneously. A 5-cm overlap was performed using intra peritoneal mesh. Fixation was performed using absorbable tacks in a double crown technique. RESULTS: One hundred and twelve cases were included. The mean age was 57 years old (range 33-81 years). Fifty-nine were females and 53 were males. The median post-operative stay for the non-fascial closure group was 0 days (range 0 12 days). The median post-operative stay for the fascial closure group was 0 days (range 0-12 days). All cases were followed up clinically at 6 weeks. In the non fascial closure group, five patients developed a seroma (12 %). One patient developed a wound infection (3 %). Six patients presented with a recurrence over the study period (15 %). In the fascial closure group, four patients had a seroma, which was managed conservatively (5 %). One patient developed a wound infection (1 %). Five patients developed a recurrence over the study period (7 %). CONCLUSION: We have shown comparable rates for seroma and recurrence to other series. Laparoscopic incisional hernia repair with defect closure is feasible and reduces seroma rate and recurrence. PMID- 27005286 TI - Strategies of laparoscopic thyroidectomy for treatment of substernal goiter via areola approach. AB - BACKGROUND: This study was aimed at exploring the feasibility and strategies of laparoscopic thyroidectomy for treatment of substernal goiter via areola approach. METHODS: A retrospective analysis was conducted to investigate 15 cases of laparoscopic resection of substernal goiter via the areola approach (laparoscopic group) and 12 cases of open resection of substernal goiter via low neck collar cervical approach (open group) that was completed between December 2012 and December 2014. Operative time, estimated blood loss, postoperative hospitalization and postoperative complication were compared. Follow-up data were assessed, and the mean duration of follow-up was 24.5 +/- 7.5 months. RESULTS: The surgery was successfully completed in 14 cases, and 1 case was intraoperatively converted to open surgery. All the procedures were successfully completed in the open group. There was no difference in the mean distance from the inferior border of the excised substernal mass to the sternal notch, operation time, intraoperative estimated blood loss, postoperative hospital stay or the drainage tubes removed. Five cases had transient hypocalcemia after surgery in the laparoscopic group, while 1 case in the open group. There were no cases of hoarseness, dysphagia, lymphatic leakage, dyspnea and death in the two groups. And there were no recurrent cases in the follow-up. CONCLUSION: Laparoscopic thyroidectomy for the treatment of selected substernal goiter via the areola approach is feasible. Preoperative B-ultrasound and 3D-CT scan reconstruction help to select cases and formulate surgical strategies, and the way that the thyroid is suspended using silk threads intraoperatively can reduce surgical difficulties and risks of intraoperative conversion to open surgery. PMID- 27005287 TI - Systematic review and meta-analysis of minimally invasive versus open approach for pancreaticoduodenectomy. AB - BACKGROUNDS AND OBJECTIVE: The technique of minimally invasive pancreatic surgeries has evolved rapidly, including minimally invasive pancreaticoduodenectomy (MIPD). However, controversy on safety and feasibility remains when comparing the MIPD with the open pancreaticoduodenectomy (OPD); therefore, we aimed to compare MIPD and OPD with a systemic review and meta analysis. METHODS: Multiple electronic databases were systematically searched to identify studies (up to February 2016) comparing MIPD with OPD. Intra-operative outcomes, oncologic data, postoperative complications and postoperative recovery were evaluated. RESULTS: Twenty-two retrospective studies including 6120 patients (1018 MIPDs and 5102 OPDs) were included. MIPD was associated with a reduction in estimated blood loss (WMD -312.00 ml, 95 % CI -436.30 to -187.70 ml, p < 0.001), transfusion rate (OR 0.41, 95 % CI 0.30-0.55, p < 0.001), wound infection (OR 0.37, 95 % CI 0.20-0.66, p < 0.001) and length of hospital stay (WMD -3.57 days, 95 % CI -5.17 to -1.98 days, p < 0.001). Meanwhile, MIPD group has a higher R0 resection rate (OR 1.47, 95 % CI 1.18-1.82, p < 0.001) and more lymph nodes harvest (WMD 1.74, 95 % CI 1.03-2.45, p < 0.001). However, it had longer operation time (WMD 83.91 min, 95 % CI 36.60-131.21 min, p < 0.001). There were no significant differences between the two procedures in morbidities (p = 0.86), postoperative pancreatic fistula (p = 0.17), delayed gastric empting (p = 0.65), vascular resection (p = 0.68), reoperation (p = 0.33) and mortality (p = 0.90). CONCLUSIONS: MIPD can be a reasonable alternative to OPD with potential advantages. However, further large-volume, well-designed RCTs with extensive follow-ups are suggested to confirm and update the findings of our analysis. PMID- 27005289 TI - Short-term outcomes of laparoscopic D2 lymphadenectomy with complete mesogastrium excision for advanced gastric cancer. AB - BACKGROUND: D2 lymphadenectomy has been widely accepted as a standard procedure of surgical treatment for local advanced gastric cancer [1, 2]. However, neither the dissection boundary nor the extent of the excision for perigastric soft tissues has been described [3-7]. Our previous researches demonstrate the existence of disseminated cancer cells in the mesogastrium [8, 9] and present an understandable mesogastrium model for gastrectomy [10]. Hence, the D2 lymphadenectomy plus complete mesogastrium excision (D2 + CME) is firstly proposed in this study, aiming to assess the safety, feasibility and corresponding short-term surgical outcomes. METHODS: All of these patients underwent laparoscopy assisted D2 + CME radical gastrectomy with a curative R0 resection, and all the operations were performed by Prof. Jianping Gong, chief of GI surgery of Tongji Hospital, Huazhong University of Science and Technology. All participants provided informed written consent to participate in the study. This study was approved by the Tongji Hospital Ethics Committee. The standard surgical procedures in the video are described as follows. Dissect along the gastrocolic ligament and then toward the left colic flexture with special made gauze. Bluntly separate the adipose tissues to find fascia plane. Expose along the plane toward the splenic inferior polar area. Precede to the origins of left gastroepiploic vessels (LGEVs), clip and cut. All the mobilized adipose tissues in this area are defined as left gastroepiploic mesentery (LGEM) [10]. Next, turn to infra-pyloric area. Dissect the fascia plane between right gastroepiploic mesentery (RGEM) and transverse mesocolon. Turn to the pancreas head, remove the covering adipose tissues, identify the superior mesentery vein and expose the origins of right gastroepiploic vessels (RGEVs). Clip and cut. All the surrounding mobilized adipose tissues are defined as RGEM [10]. Move to the superior boarder of pancreas with the stomach reflected cephalad, incise the serosa and bluntly mobilize through the plane with gauze. Turn to the common hepatic artery (CHA), remove the adherent adipose tissue. Expose the root of left gastric vein, clip and cut. Dissect the thick sheath of left gastric artery, expose at the root, trip clip and cut. All mobilized lateral adipose tissues and dorsal parts are defined as left gastric mesentery (LGM) [10]. Toward right, dissect follow the CHA and hepatic portal vein (HPV). Next, move toward the left side of LGM and dissect along the splenic artery until reaching the posterior gastric wall. Move to the anterior area of stomach and divide the lesser omentum. Clean up the adipose tissue and nerves along the lesser curvature up to the gastroesophageal junction. Expose and cut the right gastric vessels (RGVs) where the mobilized adipose tissues are defined as right gastric mesentery (RGM) [10]. Reconstruction of the alimentary tract was done by extracorporeal anastomosis. Standard recovery protocols were followed in postoperative treatments. RESULTS: Fifty-four patients between September 2014 and March 2015 have been recruited with informed consent and underwent laparoscopic D2 + CME by a single surgeon. The mean number of retrieved regional lymph nodes was 35.04 +/- 10.70 (range 14-55). The mean volume of blood loss was 12.44 +/- 22.89 ml (range 5-100). The mean laparoscopic surgery time was 127.82 +/- 17.63 min (range 110-165). The mean hospitalization time was 11.09 +/- 4.28 days (range 8-28). No operative complication was observed during the hospitalization. CONCLUSION: The anatomical boundary of mesogastrium is well described and dissected within D2 + CME surgical process. It proves to be safely feasible and repeatable with less blood lost, qualified lymph nodes retrieval results and other improved short-term surgical outcomes in advanced gastric cancer. Meanwhile, potential disseminated cancer cells fall into the mesogastrium can be eradicated by D2 + CME. PMID- 27005288 TI - Warmed and humidified carbon dioxide for abdominal laparoscopic surgery: meta analysis of the current literature. AB - BACKGROUND: The creation of a pneumoperitoneum for laparoscopic surgery is performed by the insufflation of carbon dioxide (CO2). The insufflated CO2 is generally at room temperature (20-25 degrees C) and dry (0-5 % relative humidity). However, these physical characteristics could lead to alterations of the peritoneal cavity, leading to operative and postoperative complications. Warming and humidifying the insufflated gas has been proposed to reduce the iatrogenic effects of laparoscopic surgery, such as pain, hypothermia and peritoneal alterations. Two medical devices are currently available for laparoscopic surgery with warm and humidified CO2. METHODS: Clinical studies were identified by searching PubMed with keywords relating to humidified and warmed CO2 for laparoscopic procedures. Analysis of the literature focused on postoperative pain, analgesic consumption, duration of hospital stay and convalescence, surgical techniques and hypothermia. RESULTS: Bibliographic analyses reported 114 publications from 1977 to 2015, with only 17 publications of clinical interest. The main disciplines focused on were gynaecological and digestive surgery ). Analysis of the studies selected reported only a small beneficial effect of warmed and humidified laparoscopy compared to standard laparoscopy on immediate postoperative pain and per procedure hypothermia. No difference was observed for later postoperative shoulder pain, morphine equivalent daily doses, postoperative body core temperature, recovery room and hospital length of stay, lens fogging and procedure duration. CONCLUSIONS: Only few beneficial effects on immediate postoperative pain and core temperature have been identified in this meta-analysis. Although more studies are probably needed to close the debate on the real impact of warmed and humidified CO2 for laparoscopic procedures. PMID- 27005290 TI - Local wound infiltration plus transversus abdominis plane (TAP) block versus local wound infiltration in laparoscopic colorectal surgery and ERAS program. AB - BACKGROUND: Few data are available on TAP block in laparoscopic colorectal surgery and ERAS program. The aim of this prospective study was to evaluate local wound infiltration plus TAP block compared to local wound infiltration in the management of postoperative pain, nausea and vomiting, ileus and use of opioids in the context of laparoscopic colorectal surgery and ERAS program. METHODS: From March 2014 to March 2015, 48 patients were treated by laparoscopic resection and ERAS program for colorectal cancer and diverticular disease at the Division of General and Hepatobiliary Surgery, University of Verona Hospital Trust. Among these, 24 patients received local wound infiltration plus TAP block (TAP block group) and 24 patients received local wound infiltration (control group). RESULTS: No differences were observed in baseline patient characteristics, clinical variables and surgical procedures between the two groups. Local wound infiltration plus TAP block allowed to achieve pain control despite a reduced use of opioid analgesics (P = 0.009). The adoption of TAP block resulted beneficial on the prevention of postoperative nausea (P = 0.002) and improvement of essential outcomes of ERAS program as recovery of bowel function (P = 0.005), urinary catheter removal (P = 0.003) and capability to tolerate oral diet (P = 0.027). CONCLUSIONS: TAP block plus local wound infiltration in the setting of laparoscopic colorectal surgery and ERAS program guarantees a reduced use of opioid analgesics and good pain control allowing the improvement of essential items of enhanced recovery pathways. PMID- 27005291 TI - Surgical management of postoperative chronic inguinodynia by laparoscopic transabdominal preperitoneal approach. AB - BACKGROUND: The avoidance of postoperative chronic pain is of the foremost importance and has a deep impact on patient satisfaction. The objective of this study is to evaluate the selective transabdominal preperitoneal laparoscopic neurectomy for treatment of refractory inguinodynia. METHODS: Prospective study in a University Hernia Center included 16 consecutive patients with chronic pain. Primary endpoint was pain control (measured by appropriate questionnaire and need of analgesics). Secondary endpoint was surgical morbidity. Follow-up was 2 years (range 12 months-4 years). RESULTS: The mean operating time was 52 (range 36-68) minutes, and there were no intraoperative complications. All patients had histologic confirmation of neurectomy. Anatomical variation was found in ten patients (62.5 %), being a common trunk ilioinguinal/iliohypogastric nerve the most frequent (nine patients, 56.25 %). One patient developed hypoesthesia in the territory of the femorocutaneous nerve by nerve injury. Reoperation was performed 6 months afterward to complete ilioinguinal nerve neurectomy. Neuropathic pain medications were continued by five patients. Pain was completely eliminated in 11 (68.75 %). CONCLUSIONS: Management of patients with neural groin pain should be done in a multidisciplinary unit. Selective neurectomy by a transabdominal preperitoneal laparoscopic approach is a safe and highly effective option in selected patients for the treatment of refractory postoperative chronic pain. Careful anatomical planning is essential to avoid inadvertent injuries and more suffering to these patients. PMID- 27005292 TI - Hiatal hernia and gastroesophageal reflux: Study of collagen in the phrenoesophageal ligament. AB - BACKGROUND: Gastroesophageal reflux disease (GERD) is defined by the intensity and/or quality of the reflux of gastric or duodenal contents into the esophagus. Surgical treatment of GERD has shown conflicting results and unacceptable recurrence rates, mainly due to herniation of the antireflux valve into the chest. A variety of techniques has been proposed to reduce GERD recurrence, including routine use of prosthesis in cruroplasty. The prevalence of GERD in patients with hiatal hernia (HH) can reach 94 %. It is possible that the phrenoesophageal ligament (POL) engaged in the stabilization of the gastroesophageal junction in the abdomen may be an etiological factor of HH. We conducted a study to evaluate collagen in the constitution of the POL in patients with HH and cadavers without HH. METHODS: POL samples were collected from 29 patients with HH and GERD (cases) and 32 samples from cadavers without HH (controls). Total collagen was quantified through the Picrosirius red histochemical technique, and type-I and type-III collagens were quantified immunohistochemically using a monoclonal antibody. The stained slides were photographed, and images were quantified by computer software (Image Pro Plus) to count the pixels per field. RESULTS: The mean age was 49.5 (+/-11.5) years for the cases and 38.5 (+/-13) years for the controls (p < 0.01). Seventeen cases (58.6 %) and six controls (18.75 %) were female (p < 0.01). The quantity of total (p < 0.01), type-I (p < 0.01), and type-III (p < 0.05) collagens was significantly lower by about 60 % in patients with HH compared with controls. CONCLUSION: Our data indicate that the composition of POL for patients with GERD and HH includes less total, type-I, and type-III collagens than that of the POL of cadavers without HH. The quality of the POL may be an etiological factor in the development of HH. PMID- 27005293 TI - Comparison of endoscopic submucosal dissection and surgery for the treatment of gastric submucosal tumors originating from the muscularis propria layer: a single center study (with video). AB - INTRODUCTION: Endoscopic submucosal dissection (ESD) has been used for the treatment of gastric submucosal tumors (SMTs). This study aims to compare clinical outcomes of ESD versus laparoscopic wedge resection (LWR) for gastric SMTs. METHODS: This is a retrospective cohort study. Patients with SMTs who underwent ESD or LWR were enrolled in this study at a university-affiliated hospital from January 2010 to October 2015. Preoperative endoscopic ultrasound and computed tomography were performed to determine origin of layer and growth pattern. Clinical outcomes including baseline demographics, tumor size, operation time, blood loss, hospital stay, cost, pathology and postoperative complications were compared. RESULTS: From January 2010 to October 2015, 68 patients with SMTs received ESD and 47 patients with SMTs received LWR. There was no difference in age, gender, body mass index, origin of layer and proportion with symptoms between ESD group and LWR group. However, tumor size was significantly larger in the LWR group (37.1 mm) than in the ESD group (25.8 mm, P = 0.041). For patients with tumors smaller than 20 mm, ESD was associated with shorter mean operation time (89.7 +/- 23.5 vs 117.6 +/- 23.7 min, P = 0.043), less blood loss (4.9 +/- 1.7 vs 72.3 +/- 23.3 ml, P < 0.001), shorter length of hospital stay (3.6 +/- 1.9 vs 6.9 +/- 3.7 days, P = 0.024) and lower cost (2471 +/- 573 vs 4498 +/- 1257 dollars, P = 0.031) when compared with LWR. For patients with tumors between 20 mm and 50 mm, ESD was associated with shorter mean operation time (99.3 +/- 27.8 vs 125.2 +/- 31.5 min, P = 0.039), less blood loss (10.1 +/- 5.3 vs 87.6 +/- 31.3 ml, P < 0.001), shorter length of hospital stay (4.0 +/- 1.7 vs 7.3 +/- 4.5 days, P = 0.027) and lower cost (2783 +/- 601 vs 4798 +/- 1343 dollars, P = 0.033) when compared with LWR. There were no significant differences in terms of rates of en bloc resection, complete resection and complication and histological diagnosis regardless of tumor size. CONCLUSIONS: ESD can achieve similar oncological outcomes when compared with surgery for treatment of gastric SMT smaller than 50 mm. PMID- 27005294 TI - Etomidate plus propofol versus propofol alone for sedation during gastroscopy: a randomized prospective clinical trial. AB - BACKGROUND AND AIMS: Sedation with propofol alone during gastroscopy has many side effects. Etomidate has advantages in terms of circulation and respiration compared to propofol. We hypothesized that etomidate plus propofol during gastroscopy would be more safe and effective than propofol alone. METHODS: Four hundred (n = 400) patients were randomly divided into a propofol group (P group) and a etomidate plus propofol group (EP group). The P group was given the first dose of 1 % propofol 1 mg/kg before gastroscopy, and the EP group was given 1 % propofol 0.5 mg/kg plus etomidate 0.1 mg/kg. Repeated doses of 10-20 mg propofol or 5-10 mg propofol plus 1-2 mg etomidate were administered to maintain an adequate level of sedation. The sedation depth was maintained by bispectral index value of 40-60. RESULTS: The EP group had a lower incidence of systolic hypotension (13.0 vs. 32.5 %; P < 0.0001), bradycardia (8.5 vs. 16.5 %; P = 0.0226), mild hypoxemia (6.5 vs. 18.0 %; P = 0.0007), and severe hypoxemia (2.5 vs. 10.0 %; P = 0.0031) compared to the P group. Also, the satisfaction of anesthetist and gastroscopist with EP was higher than that of P group (P < 0.0001; P = 0.018, respectively). CONCLUSION: Etomidate plus propofol had few effects on respiration and circulation in patients undergoing gastroscopy and was more safe and effective than propofol alone. PMID- 27005295 TI - Pushing the envelope: laparoscopy and primary anastomosis are technically feasible in stable patients with Hinchey IV perforated acute diverticulitis and gross faeculent peritonitis. AB - INTRODUCTION: Modern management of severe acute complicated diverticulitis continues to evolve towards more conservative and minimally invasive strategies. Although open sigmoid colectomy with end colostomy remains the most commonly used procedure for the treatment of perforated diverticulitis with purulent/faeculent peritonitis, recent major advances challenged this traditional approach, including the increasing attitude towards primary anastomosis as an alternative to end colostomy and use of laparoscopic approach for urgent colectomy. TECHNIQUE: Provided an accurate patients selection, having the necessary haemodynamic stability, pneumoperitoneum is established with open Hasson technique and diagnostic laparoscopy is performed. If faeculent peritonitis (Hinchey IV perforated diverticulitis) is found, laparoscopy can be continued and a further three working ports are placed using bladeless trocars, as in traditional laparoscopic sigmoidectomy, with the addition of fourth trocar in left flank. The feacal matter is aspirated either with large-size suction devices or, in case of free solid stools, these can be removed with novel application of tight sealing endobags, which can be used for scooping the feacal content out and for its protected retrieval. After decontamination, a sigmoid colectomy is performed in the traditional laparoscopic fashion. The sigmoid is fully mobilised from the retroperitoneum, and mesocolon is divided up to the origin of left colic vessels. Whenever mesentery has extremely inflamed and thickened oedematous tissues, an endostapler with vascular load can be used to avoid vascular selective ligatures. Splenic flexure should be appropriately mobilised. The specimen is extracted through mini-Pfannenstiel incision with muscle splitting technique. Transanal colo-rectal anastomosis is fashioned. Air-leak test must be performed and drains placed where appropriate. RESULTS: The video shows operative technique for a single-stage, entirely laparoscopic, washout and sigmoid colectomy with primary colorectal anastomosis in a 35-year-old male patient with severe and diffuse free faeculent diverticular peritonitis (Hinchey IV). The patient was managed post-operatively according to enhanced recovery protocol and discharged home after 9 days, following an uneventful recovery. CONCLUSIONS: This case documents the technical feasibility of a minimally invasive single-stage procedure in a patient with Hinchey IV perforated diverticulitis with diffuse feacal peritonitis. The laparoscopic approach facilitated an effective decontamination of the peritoneal cavity, with a combination of large suction devices and aid of protected retrieval by closed endobags for effectively and completely laparoscopic removal of the solid feacal matter, offering clear advantages and excellent results even in such challenging cases. With necessary expertise, the sigmoid resection can be thereafter safely and entirely performed laparoscopically, the specimen extracted through mini-Pfannenstiel incision, and a laparoscopic intracorporeal transanal circular primary anastomosis performed. PMID- 27005296 TI - Intrahepatic cholangiocarcinoma in a patient with Wilson's disease: a case report. AB - The incidence of hepatobiliary malignancies, and especially intrahepatic cholangiocarcinoma (ICC), for patients with Wilson's disease (WD), is very low, even for cirrhotic patients. A 44-year-old male was admitted to our department for treatment of a liver tumor. He was diagnosed with WD at the age of 15. According to radiological findings, his liver tumor was a suspected hepatocellular carcinoma (HCC) or a combined hepatocellular and cholangiocellular carcinoma. A partial resection of liver segments 8 (S8) and 5 (S5) was subsequently performed due to the intraoperative suspicion of intrahepatic metastasis at the surface of S5. Postoperative histology revealed that the resected portion of S8 contained an ICC; the removed S5 portion comprised a regenerative nodule with hemosiderosis. To date, the patient has survived without tumor recurrence for more than 44 months following surgery. A survey of the literature, inclusive of case reports, would suggest that surgical resection is the primary course of action for a WD patient with ICC, if liver function can be preserved and curative resection performed. PMID- 27005297 TI - Associations between the toe brachial index and health-related quality of life in older people. AB - BACKGROUND: Peripheral arterial disease is responsible for impaired health related quality of life as a consequence of associated morbidity and mortality. The toe brachial index (TBI) provides non-invasive assessment of peripheral arterial health. Lower TBI values have been associated with foot ulceration, amputation and impaired healing, however, the relationship with health-related quality of life has not yet been investigated. The aim of this study was to explore the relationship between the TBI and health-related quality of life. METHODS: This was a cross-sectional study of 100 participants aged over 50 years recruited from podiatry clinics in New South Wales, Australia. The TBI was calculated using automated equipment and quality of life was assessed using the Short Form 36 version 2 (SF-36v2). Strength of associations was determined using Pearson and Spearman correlation coefficients. RESULTS: Lower TBI values demonstrated modest significant associations with poorer scores for the SF-36v2 domains Role Physical (r s = 0.219, p > 0.05), Social Function (r s = 0.219, p < 0.05) and the Physical Component Summary score (r s = 0.203, p < 0.05). CONCLUSIONS: The toe brachial index demonstrates limited associations with physical and social aspects of health-related quality of life in older people. PMID- 27005298 TI - Exact tests in binary data under an incomplete block crossover design. AB - To improve the power of a parallel groups design and reduce the time length of a crossover trial, we may consider an incomplete block crossover design. Under a distribution-free random effects logistic regression model, we derive an exact test and a Mantel-Haenszel Type of summary test procedure for testing non equality in binary data when comparing three treatments. We employ Monte Carlo simulation to evaluate the performance of these test procedures. We find that both test procedures developed here can perform well in a variety of situations. We use the data taken as a part of the crossover trial comparing the low and high doses of an analgesic with a placebo for the relief of pain in primary dysmenorrhea to illustrate the use of the proposed test procedures. PMID- 27005299 TI - Intracerebellar vermis histamine facilitates memory consolidation in the elevated T maze model. AB - Experimental evidence suggests that the cerebellum plays a more complex role in learning than simply regulating the motor response. Rather, it is thought to play a significant role in the consolidation of emotional memory in mice. Due to the difficulty of interpreting fear and anxiety behaviors-the standard methodology for the study of the histaminergic system and emotional memory-in mice, we propose a behavioral assessment of mice subjected to the Elevated T-maze after histamine microinjection of the cerebellar vermis. Young male Swiss albino mice weighing 25-35g were used. In addition, locomotor activity was tested in an open field test. Our data suggest that histamine did not affect memory consolidation during escape or open field behavior at the doses used in this study. However, we observed a significant increase in inhibitory avoidance on the second day in animals receiving a dose of 6.8nmol/0.5MUl, suggesting that histamine facilitates the consolidation of inhibitory avoidance in mice. PMID- 27005300 TI - The 2015 hospital treatment choice reform in Norway: Continuity or change? AB - In several European countries, including Norway, polices to increase patient choice of hospital provider have remained high on the political agenda. The main reason behind the interest in hospital choice reforms in Norway has been the belief that increasing choice can remedy the persistent problem of long waiting times for elective hospital care. Prior to the 2013 General Election, the Conservative Party campaigned in favour of a new choice reform: "the treatment choice reform". This article describes the background and process leading up to introduction of the reform in the autumn of 2015. It also provides a description of the content and discusses possible implications of the reform for patients, providers and government bodies. In sum, the reform contains elements of both continuity and change. The main novelty of the reform lies in the increased role of private for-profit healthcare providers. PMID- 27005301 TI - Biomechanical investigation of a minimally invasive posterior spine stabilization system in comparison to the Universal Spinal System (USS). AB - BACKGROUND: Although minimally invasive posterior spine implant systems have been introduced, clinical studies reported on reduced quality of spinal column realignment due to correction loss. The aim of this study was to compare biomechanically two minimally invasive spine stabilization systems versus the Universal Spine Stabilization system (USS). METHODS: Three groups with 5 specimens each and 2 foam bars per specimen were instrumented with USS (Group 1) or a minimally invasive posterior spine stabilization system with either polyaxial (Group 2) or monoaxial (Group 3) screws. Mechanical testing was performed under quasi-static ramp loading in axial compression and torsion, followed by destructive cyclic loading run under axial compression at constant amplitude and then with progressively increasing amplitude until construct failure. Bending construct stiffness, torsional stiffness and cycles to failure were investigated. RESULTS: Initial bending stiffness was highest in Group 3, followed by Group 2 and Group 1, without any significant differences between the groups. A significant increase in bending stiffness after 20'000 cycles was observed in Group 1 (p = 0.002) and Group 2 (p = 0.001), but not in Group 3, though the secondary bending stiffness showed no significant differences between the groups. Initial and secondary torsional stiffness was highest in Group 1, followed by Group 3 and Group 2, with significant differences between all groups (p <= 0.047). A significant increase in initial torsional stiffness after 20'000 cycles was observed in Group 2 (p = 0.017) and 3 (p = 0.013), but not in Group 1. The highest number of cycles to failure was detected in Group 1, followed by Group 3 and Group 2. This parameter was significantly different between Group 1 and Group 2 (p = 0.001), between Group 2 and Group 3 (p = 0.002), but not between Group 1 and Group 3. CONCLUSIONS: These findings quantify the correction loss for minimally invasive spine implant systems and imply that unstable spine fractures might benefit from stabilization with conventional implants like the USS. PMID- 27005302 TI - Methotrexate improves pro- and anti-atherogenic genomic expression in psoriatic skin. PMID- 27005303 TI - Formula diet alters small intestine morphology, microbial abundance and reduces VE-cadherin and IL-10 expression in neonatal porcine model. AB - BACKGROUND: Breastfeeding is associated with a variety of positive health outcomes in children and is recommended exclusively for the first 6 months of life; however, 50-70 % of infants in the US are formula-fed. To test the hypothesis that immune system development and function in neonates and infants are significantly influenced by diet, 2-day old piglets were fed soy or milk formula (n = 6/group/gender) until day 21 and compared to a sow-fed group (n = 6/gender). METHODS: Histomorphometric analyses of ileum, jejunum and Peyer's patches were carried out, to determine the inflammation status, mRNA and protein expression of pro-inflammatory, anti-inflammatory and growth-related chemokines and cytokines. RESULTS: In formula-fed animals, increases in ileum and jejunum villus height and crypt depth were observed in comparison to sow-fed animals (jejunum, p < 0.01 villus height, p < 0.04 crypt depth; ileum p < 0.001 villus height, p < 0.002 crypt depth). In formula-fed the lymphoid follicle size (p < 0.01) and germinal centers (p < 0.01) with in the Peyer's patch were significantly decreased in comparison to sow-fed, indicating less immune education. In ileum, formula diet induced significant up-regulation of AMCFII, IL 8, IL-15, VEGFA, LIF, FASL, CXCL11, CCL4, CCL25 and down-regulation of IL-6, IL 9, IL-10, IL-27, IFNA4, CSF3, LOC100152038, and LOC100736831 at the transcript level. We have confirmed some of the mRNA data by measuring protein, and significant down-regulation of anti-inflammatory molecule IL-10 in comparison to sow-fed piglets was observed. To further determine the membrane protein expression in the ileum, VE-cadherin, occludin, and claudin-3, Western blot analyses were conducted. Sow fed piglets showed significantly more VE-Cadherin, which associated with levels of calcium, and putrescine measured. It is possible that differences in GI tract and immune development are related to shifts in the microbiome; notably, there were 5-fold higher amounts of Lactobacillaceae spp and 3 fold higher Clostridia spp in the sow fed group in comparison to milk formula fed piglets, whereas in milk formula-fed pigs Enterobacteriaceae spp was 5-fold higher. CONCLUSION: In conclusion, formula diet alters GI morphology, microbial abundance, intestinal barrier protein VE-cadherin and anti-inflammatory molecule IL-10 expression. Further characterization of formula effects could lead to modification of infant formula to improve immune function, reduce inflammation and prevent conditions such as allergies and infections. PMID- 27005304 TI - Nodding syndrome and epilepsy in onchocerciasis endemic regions: comparing preliminary observations from South Sudan and the Democratic Republic of the Congo with data from Uganda. AB - BACKGROUND: Nodding syndrome (NS) is an epilepsy disorder occurring in children in South Sudan, northern Uganda and Tanzania. The etiology of NS is unknown, but epidemiological studies demonstrate an association between NS and onchocerciasis. METHODS: Between November 2013 and July 2015 we visited onchocerciasis endemic regions in South Sudan, Uganda, and the Democratic Republic of the Congo (DRC) to assess the epilepsy situation. In South Sudan we interviewed patients and affected families, health officials, colleagues and healthcare workers, and performed a small household survey to estimate the epilepsy prevalence in the village of Mvolo, Western Equatoria State. Most information from Uganda was collected through discussions with colleagues and a review of published literature and reports. In the Bas-Uele district of the DRC, we visited the villages of Liguga, Titule and Dingila, interviewed patients with epilepsy and family members and conducted a preliminary entomological assessment. RESULTS: In South Sudan there is an ongoing NS and epilepsy epidemic in the Western Equatoria state that started around 1990. A survey of 22 households in Mvolo revealed that 28 out of 168 (16.7%) children suffered from NS or another form of epilepsy. Thirteen (59%) households had at least one child, and nine (41%) households at least two children with NS or another form of epilepsy. In northern Uganda, an NS and epilepsy epidemic started around 2000. The occurrence of new NS cases has been in decline since 2008 and no new NS cases were officially reported in 2013. The decline in NS cases coincided with the bi-annual distribution of ivermectin and the treatment of blackfly-breeding rivers with larvicides. In Bas-Uele district in the DRC, epilepsy appears to be endemic with cases clustered in villages close to blackfly-infested, rapid-flowing rivers. The majority of epilepsy cases in Liguga, Dingila and Titule presented with generalized (tonic clonic) seizures without nodding, but with mental retardation. In Titule, an epilepsy prevalence of 2.3% was documented. The only anthropophilic species of blackfly collected in the region belonged to the Simulium damnosum complex. CONCLUSION: Blackflies may play a key role in the transmission of an etiological agent that either directly or indirectly cause, not only NS, but also other forms of epilepsy in onchocerciasis endemic regions. PMID- 27005305 TI - EGCG stabilizes growth cone filopodia and impairs retinal ganglion cell axon guidance. AB - BACKGROUND: Antioxidants such as the green tea polyphenol epigallocatechin gallate (EGCG) are neuroprotective under many conditions in mature nervous systems; however, their impact has rarely been explored in developing nervous systems, in which a critical step is the formation of connections between neurons. Axons emerge from newly formed neurons and are led by a dynamic structure found at their tip called a growth cone. Here we explore the impact of EGCG on the development of retinal ganglion cell (RGC) axons, which connect the eye to the brain. RESULTS: EGCG acts directly on RGC axons to increase the number of growth cone filopodia, fingerlike projections that respond to extrinsic signals, in vitro and in vivo. Furthermore, EGCG exposure leads to a dramatic defect in the guided growth of RGC axons where the axons fail to make a key turn in the mid-diencephalon required to reach their target. Intriguingly, at guidance points where RGCs do not show a change in direction, EGCG has no influence on RGC axon behavior. CONCLUSIONS: We propose that EGCG stabilizes filopodia and prevents normal filopodial dynamics required for axons to change their direction of outgrowth at guidance decision points. Developmental Dynamics 245:667-677, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27005306 TI - A scoping review of studies comparing the medication event monitoring system (MEMS) with alternative methods for measuring medication adherence. AB - Different methods are available for measuring medication adherence. In this paper, we conducted a scoping review to identify and summarize evidence of all studies comparing the Medication Event Monitoring System (MEMS) with alternative methods for measuring medication adherence. A literature search was performed using the open database www.iAdherence.org that includes all original studies reporting findings from the MEMS. Papers comparing methods for measuring adherence to solid oral formulations were included. Data was extracted using a standardized extraction table. A total of 117 articles fulfilled the inclusion criteria, including 251 comparisons. Most frequent comparisons were against self report (n = 119) and pill count (n = 59). Similar outcome measures were used in 210 comparisons (84%), among which 78 used dichotomous variables (adherent or not) and 132 used continuous measures (adherence expressed as percentage). Furthermore, 32% of all comparisons did not estimate adherence over the same coverage period and 44% of all comparisons did not use a statistical method or used a suboptimal one. Only eighty-seven (35%) comparisons had similar coverage periods, similar outcome measures and optimal statistical methods. Compared to MEMS, median adherence was grossly overestimated by 17% using self-report, by 8% using pill count and by 6% using rating. In conclusion, among all comparisons of MEMS versus alternative methods for measuring adherence, only a few used adequate comparisons in terms of outcome measures, coverage periods and statistical method. Researchers should therefore use stronger methodological frameworks when comparing measurement methods and be aware that non-electronic measures could lead to overestimation of medication adherence. PMID- 27005307 TI - A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients. AB - The lack of head-to-head clinical studies powered to compare atomoxetine and osmotic release oral system (OROS) methylphenidate necessitates treatment comparison by methods that include indirect evidence such as network meta analysis (NMA). A NMA assessing the relative treatment effects of atomoxetine and OROS methylphenidate in adults with attention-deficit/hyperactivity disorder (ADHD) was conducted. Studies were identified by systematic literature review. Analyses summarised improvements in efficacy, measured by ADHD-specific scales, using Cohen'sdto calculate the standardised mean difference (SMD), and all cause discontinuations. Results showed effect sizes (SMD, 95% credible interval (CrI)) relative to placebo that did not differ significantly between atomoxetine (0.46, 0.36-0.56) and OROS methylphenidate (0.51, 0.40-0.63) in clinical studies of up to 12 weeks' duration (SMD, 95% CrI for atomoxetine versus OROS methylphenidate: 0.05, -0.18-0.08). Patients treated with these medications responded better than those given placebo across all analyses. There was also no significant difference in discontinuation rates between atomoxetine and OROS methylphenidate (odds ratio, 95% CrI: 0.85, 0.53-1.35). Between-study heterogeneity was low overall. Results of this NMA suggest that the efficacy of atomoxetine and OROS methylphenidate in adults does not differ significantly. Clinical guidelines may require amendment to reflect these recent data. PMID- 27005308 TI - gamma-aminobutyric acid as a metabolite: Interpreting magnetic resonance spectroscopy experiments. AB - The current rise in the prevalence of magnetic resonance spectroscopy experiments to measure gamma-aminobutyric acid in the living human brain is an exciting and productive area of research. As research spreads into clinical populations and cognitive research, it is important to fully understand the source of the magnetic resonance spectroscopy signal and apply appropriate interpretation to the results of the experiments. gamma-aminobutyric acid is present in the brain not only as a neurotransmitter, but also in high intracellular concentrations, both as a transmitter precursor and a metabolite. gamma-aminobutyric acid concentrations measured by magnetic resonance spectroscopy are not necessarily implicated in neurotransmission and therefore may reflect a very different brain activity to that commonly suggested. In this perspective, we examine some of the considerations to be taken in the interpretation of any gamma-aminobutyric acid signal measured by magnetic resonance spectroscopy. PMID- 27005309 TI - CB1 antagonism produces behaviors more consistent with satiety than reduced reward value in food-maintained responding in rats. AB - Cannabinoid CB1 antagonists are widely known to reduce motivation for food, but it is not known whether they induce satiety or reduce reward value of food. It may therefore be necessary to compare effects of altered satiety and reward food value in the same appetitive task, and determine whether CB1 antagonism produces a behavior pattern similar to either, both, or neither. A fine-grained analysis of fixed-ratio 10 (FR10) responding for palatable food initially included number and duration of, and between, all lever presses and food tray entries in order to differentiate the pattern of suppression of prefeeding from that caused by reducing the reward value of the pellets with quinine. Discriminant function analysis then determined that these manipulations were best differentiated by effects on tray entries, pellet retrieval latencies, and time of the first response. At 0.5 mg/kg, AM 6527 produced similar effects to reducing reward value, but at 1.0 and 4.0 mg/kg, effects were more similar to those when animals were satiated. We conclude that AM 6527 both reduced reward value and enhanced satiety, but as dose increased, effects on satiety became much more prominent. These findings contribute to knowledge about the behavioral processes affected by CB1 antagonism. PMID- 27005310 TI - Comparing episodes of antidepressants use with intermittent episodes of no use: A higher relative risk of suicide attempts but not of suicide at young age. AB - The Food and Drug Administration has issued a number of advisories regarding a possible causal link between antidepressants and suicide behaviour among young persons. We investigated the age dependency of (fatal) suicide attempts associated with antidepressants (N=232,561). By linking insurance claims with the death register of Statistics Netherlands (2002-2011), rates of (fatal) suicide attempts were estimated during antidepressant use and intermittent episodes without use. The age dependency of the relative risk of attempts and of suicide during episodes with compared with episodes without antidepressants was investigated by testing the {age * episode} interaction.The attempt rate during antidepressant use decreased with increasing age, concurrently with a decrease of the relative risk from 3.62 to 1.86 (p for interaction <0.001). This age dependency was found both at the early (<0.5 year) and at later stages after the first prescription (>5 years). No suicides were found among those aged <18 years, and no age dependency for the relative risk of suicide at ages ? 18 was established (p>0.46). The association between antidepressants and suicide attempts at a young age does not necessarily point to a causal relationship, and, most importantly, did not translate to a similar age dependency for suicide. PMID- 27005311 TI - Biallelic editing of a lamprey genome using the CRISPR/Cas9 system. AB - Lampreys are extant representatives of agnathans. Descriptions of lamprey development, physiology and genome have provided critical insights into early evolution of vertebrate traits. However, efficient means for genetic manipulation in agnathan species have not been developed, hindering functional studies of genes in these important Evo-Devo models. Here, we report a CRISPR/Cas system optimized for lamprey genomes and use it to disrupt genomic loci in the Northeast Chinese lamprey (Lethenteron morii) with efficiencies ranging between 84~99%. The frequencies of indels observed in the target loci of golden (gol), kctd10, wee1, soxe2, and wnt7b, estimated from direct sequencing of genomic DNA samples of injected lamprey larvae, were 68/69, 47/56, 38/39, 36/37 and 36/42, respectively. These indels often occurred in both alleles. In the CRISPR/Cas9 treatment for gol or kctd10, 38.6% or 85.3% of the targeted larvae had the respective recessive null-like phenotypes, further confirming the disruption of both loci. The kctd10 gRNA, designed against an essential functional region of Kctd10, resulted in null like phenotypes and in-frame mutations in alleles. We suggest that the CRISPR/Cas based approach has the potential for efficient genetic perturbation in organisms less amenable to germ line transmission based approaches. PMID- 27005312 TI - Cell-targeting antibodies in immunity to Ebola. AB - As the 2014-15 Ebola virus epidemic in West Africa evolved from emergency to lesson, developers of both vaccines and therapeutic antibodies were left with the puzzlement of what kinds of anti-Ebola antibodies are predictably desirable in treating the afflicted, and what antibodies might account for the specific and lasting protection elicited by the more effective vaccines. The facile answer in virology is that neutralizing antibody (NAb) is desired and required. However, with Ebola and other filoviruses (as with many prior viral examples), there are multiple discordances in which neutralizing antibodies fail to protect animals, and others in which antibody-mediated protection is observed in the absence of measured virus neutralization. Explanation presumably resides in the protective role of antibodies that bind and functionally 'target' virus-infected cells, here called 'cell-targeting antibody', or CTAb. To be clear, many NAbs are also CTAbs, and in the case of Ebola the great majority of NAbs are likely CTAbs. Isotype, glycosylation, and other features of CTAbs are likely crucial in their capacity to mediate protection. Overall, results and analysis invite an increasingly complex view of antibody-mediated immunity to enveloped viruses. PMID- 27005313 TI - Identification of amino acid variation in the prion protein associated with classical scrapie in Canadian dairy goats. AB - BACKGROUND: A clear association of amino acid variation in the prion protein gene (PRNP) with susceptibility and resistance to classical scrapie exists in sheep, but not in goats. In this study we examined DNA sequence variation in the PRNP of 149 animals from two scrapie-infected herds of Saanen dairy goats, and identified 6 non-synonymous variants in the coding region. RESULTS: In the larger herd, all of the 54 scrapie-affected goats tested had at least one allele with the arginine (R) codon at position 211, with 52 being homozygous for that variant. No animal homozygous for the glutamine (Q) codon at 211 were affected and only two heterozygotes (R/Q) were affected. A weak association was found at position 146 and no significant associations were found with amino acid variation at the remaining four variant positions (142, 143, 222 and 240), however, the allelic variation was low. Similar patterns were observed in the second scrapie-affected herd. CONCLUSION: We also evaluated previous studies on goat herds affected with scrapie and this relationship of R susceptibility and Q resistance at 211 was present independent of the genotypes at the other positions including 222. The fact that glutamine at 211 provides a significant protective property to scrapie irrespective of the other positions could be important for breeding strategies aimed at improving herd resistance to scrapie, while maintaining important productivity traits. PMID- 27005314 TI - Tonsillectomy for adult obstructive sleep apnea: A systematic review and meta analysis. AB - OBJECTIVES/HYPOTHESIS: To determine if sleepiness and sleep study variables (e.g., Apnea-Hypopnea Index [AHI] and lowest oxygen saturation) improve following isolated tonsillectomy for adult obstructive sleep apnea (OSA). STUDY DESIGN: Systematic review and meta-analysis. METHODS: Nine databases (PubMed/MEDLINE included) were searched through November 24, 2015. RESULTS: Seventeen studies (n = 216 patients, 34.4 +/- 10.0 years and body mass index: 29.0 +/- 6.1 kg/m(2) ) met criteria. Tonsils sizes were hypertrophied, large, enlarged, extremely enlarged, or grades 2 to 4. Apnea-Hypopnea Index decreased by 65.2% (from 40.5 +/ 28.9/hour to 14.1 +/- 17.1/hour) (n = 203). The AHI mean difference (MD) was 30.2 per hour (95% confidence interval [CI] -39.3, -21.1) (P value < 0.00001). The AHI SMD was -1.37 (-1.65, -1.09) (large effect). Lowest oxygen saturation improved from 77.7 +/- 11.9% to 85.5 +/- 8.2% (n = 186). Lowest oxygen saturation MD was 8.5% (95% CI 5.2, 11.8) (P value < 0.00001). The Epworth Sleepiness Scale decreased from 11.6 +/- 3.7 to 6.1 +/- 3.9 (P value < 0.00001) (n = 125). Individual patient outcomes (n = 54) demonstrated an 85.2% success rate (AHI < 20/hour and >= 50% reduction) and a 57.4% cure rate. Individual patient data meta analysis showed preoperative AHI < 30 per hour to be a significant predictor of surgical success (P value < 0.001) and cure (P value = 0.043); among patients with preoperative AHI < 30 per hour, tonsillectomy success rate was 100% (25 of 25) and cure rate was 84% (21 of 25) with a mean postoperative AHI of 2.4 +/- 2.1 per hour; this compares to tonsillectomy success rate of 72.4% (21 of 29), cure rate of 10 of 29 (34.4%), and mean postoperative AHI of 14.3 +/- 13.9 per hour for patients with preoperative AHI >= 30 per hour. CONCLUSION: Isolated tonsillectomy can be successful as treatment for adult OSA, especially among patients with large tonsils and mild to moderate OSA (AHI < 30/hour). Laryngoscope, 2016 Laryngoscope, 126:2176-2186, 2016. PMID- 27005315 TI - Rapid growth and short life spans characterize pipefish populations in vulnerable seagrass beds. AB - The life-history traits of two species of pipefish (Syngnathidae) from seagrass meadows in New South Wales, Australia, were examined to understand whether they enhance resilience to habitat degradation. The spotted pipefish Stigmatopora argus and wide-bodied pipefish Stigmatopora nigra exhibit some of the shortest life spans known for vertebrates (longevity up to 150 days) and rapid maturity (male S. argus 35 days after hatching (DAH) and male S. nigra at 16-19 DAH), key characteristics of opportunistic species. Growth rates of both species were extremely rapid (up to 2 mm day(-1) ), with seasonal and sex differences in growth rate. It is argued that short life spans and high growth rates may be advantageous for these species, which inhabit one of the most threatened marine ecosystems on earth. PMID- 27005316 TI - Determinants of stoma reversal in rectal cancer patients who had an anterior resection between 2009 and 2012 in the English National Health Service. AB - AIM: The rate of ileostomy reversal was estimated in patients undergoing an elective anterior resection for rectal cancer and factors associated with reversal were identified. METHOD: The records of 4879 rectal patients who had an ileostomy created during anterior resection between 2009 and 2012 were identified in the National Bowel Cancer Audit database and linked to administrative records of the Hospital Episode Statistics. Patients were followed from surgery. Multivariable proportional hazards regression was used to estimate the impact of patient and cancer characteristics on ileostomy reversal with death as the competing risk. RESULTS: Within 18 months from anterior resection, 3536 (72.5%) patients had undergone ileostomy reversal. The reversal rate was lower in the following circumstances: older patients [hazard ratio (HR) 0.90; 95% CI 0.84 0.96, aged 80 vs 70 years], male gender (HR 0.90; 0.84-0.97), higher American Society of Anesthesiologists (ASA) grade (HR 0.64; 0.56-0.74, ASA 3+ vs 1), more advanced cancer (HR 0.77; 0.69-0.87, T3 vs T1), socioeconomic deprivation (HR 0.83; 0.74-0.93, most vs least deprived quintile), comorbidity (HR 0.92; 0.84 1.00, one vs no comorbidity) and open surgical procedure (HR 0.90; 0.84-0.97, open vs laparoscopic). CONCLUSION: Overall, two-thirds of ileostomies were reversed within 18 months. Reversal rates were linked to patient and cancer characteristics (age, sex, fitness and stage), mode of surgical access and socioeconomic deprivation. Observed lower reversal rates in patients from poorer backgrounds may indicate inequity in access. PMID- 27005317 TI - In-depth sphingomyelin characterization using electron impact excitation of ions from organics and mass spectrometry. AB - Electron impact excitation of ions from organics (EIEIO), also referred to as electron-induced dissociation, was applied to singly charged SM molecular species in the gas phase. Using ESI and a quadrupole TOF mass spectrometer equipped with an electron-ion reaction device, we found that SMs fragmented sufficiently to identify their lipid class, acyl group structure, and the location of double bond(s). Using this technique, nearly 200 SM molecular species were found in four natural lipid extracts: bovine milk, porcine brain, chicken egg yolk, and bovine heart. In addition to the most common backbone, d18:1, sphingosines with a range of carbon chain lengths, sphingadienes, and some sphinganine backbones were also detected. Modifications in natural SMs were also identified, including addition of iodine/methanol across a carbon-carbon double bond. This unparalleled new approach to SM analysis using EIEIO-MS shows promise as a unique and powerful tool for structural characterization. PMID- 27005318 TI - Skeletal Characteristics of WNT1 Osteoporosis in Children and Young Adults. AB - WNT proteins comprise a 19-member glycoprotein family that act in several developmental and regenerative processes. In bone, WNT proteins regulate osteoblast differentiation and maintain bone health by activating the canonical WNT/beta-catenin pathway. We reported a heterozygous missense mutation c.652T>G (p.C218G) in WNT1 exon 4 as the cause for severe early-onset, autosomal dominant osteoporosis. The initial study concerned a large Finnish family with 10 affected adults. Here we report clinical findings of the WNT1 osteoporosis in 8 children and young adults (median age 14 years; range 10 to 30 years) in two families, all with the p.C218G mutation in WNT1. Clinical assessments showed no apparent dysmorphia or features similar to typical osteogenesis imperfecta (OI). Biochemistry revealed no changes in parameters of calcium metabolism and bone turnover markers. Fracture frequencies varied, but all subjects had sustained at least one fracture and 4 had a pathological fracture history. Plain radiographs showed osteopenic appearance, loss in vertebral height, and thin diaphyses of the long bones. Bone densitometry showed the BMD to be below normal median in all subjects and the bone mass deficit seemed to be more severe in older participants. Bone histomorphometry revealed a low turnover osteoporosis in 2 subjects at ages 14 and 16 years. These findings are congruent with earlier findings in adult patients and indicate that WNT1 osteoporosis causes significant skeletal changes already in early childhood and impairs bone mass gain during pubertal years. Genetic testing of children or close relatives of affected individuals is recommended for appropriate preventive measures. (c) 2016 American Society for Bone and Mineral Research. PMID- 27005319 TI - Apelin-13 administration protects against ischaemia/reperfusion-mediated apoptosis through the FoxO1 pathway in high-fat diet-induced obesity. AB - BACKGROUND AND PURPOSE: Apelin-13, an endogenous ligand for the apelin (APJ) receptor, behaves as a potent modulator of metabolic and cardiovascular disorders. Here, we examined the effects of apelin-13 on myocardial injury in a mouse model combining ischaemia/reperfusion (I/R) and obesity and explored their underlying mechanisms. EXPERIMENTAL APPROACH: Adult male C57BL/6J mice were fed a normal diet (ND) or high-fat diet (HFD) for 6 months and then subjected to cardiac I/R. The effects of apelin-13 post-treatment on myocardial injury were evaluated in HFD-fed mice after 24 h I/R. Changes in protein abundance, phosphorylation, subcellular localization and mRNA expression were determined in cardiomyoblast cell line H9C2, primary cardiomyocytes and cardiac tissue from ND- and HFD-fed mice. Apoptosis was evaluated by TUNEL staining and caspase-3 activity. Mitochondrial ultrastructure was analysed by electron microscopy. KEY RESULTS: In HFD-fed mice subjected to cardiac I/R, i.v. administration of apelin 13 significantly reduced infarct size, myocardial apoptosis and mitochondrial damage compared with vehicle-treated animals. In H9C2 cells and primary cardiomyocytes, apelin-13 induced FoxO1 phosphorylation and nuclear exclusion. FoxO1 silencing by siRNA abolished the protective effects of apelin-13 against hypoxia-induced apoptosis and mitochondrial ROS generation. Finally, apelin deficiency in mice fed a HFD resulted in reduced myocardial FoxO1 expression and impaired FoxO1 distribution. CONCLUSIONS AND IMPLICATIONS: These data reveal apelin as a novel regulator of FoxO1 in cardiac cells and provide evidence for the potential of apelin-13 in prevention of apoptosis and mitochondrial damage in conditions combining I/R injury and obesity. PMID- 27005320 TI - Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations. AB - Voltage-gated ether a go-go (EAG) K(+) channels are expressed in various types of cancer cells and also in the central nervous system. Aberrant overactivation of human EAG1 (hEAG1) channels is associated with cancer and neuronal disorders such as Zimmermann-Laband and Temple-Baraitser syndromes. Although hEAG1 channels are recognized as potential therapeutic targets, regulation of their functional properties is only poorly understood. Here, we show that the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) is a potent inhibitory gating modifier of hEAG1 channels. PIP2 inhibits the channel activity by directly binding to a short N-terminal segment of the channel important for Ca(2+)/calmodulin (CaM) binding as evidenced by bio-layer interferometry measurements. Conversely, depletion of endogenous PIP2 either by serotonin induced phospholipase C (PLC) activation or by a rapamycin-induced translocation system enhances the channel activity at physiological membrane potentials, suggesting that PIP2 exerts a tonic inhibitory influence. Our study, combining electrophysiological and direct binding assays, demonstrates that hEAG1 channels are subject to potent inhibitory modulation by multiple phospholipids and suggests that manipulations of the PIP2 signaling pathway may represent a strategy to treat hEAG1 channel-associated diseases. PMID- 27005322 TI - Spinous alpha-Fe2O3 hierarchical structures anchored on Ni foam for supercapacitor electrodes and visible light driven photocatalysts. AB - Spinous alpha-Fe2O3 hierarchical structures grown on a Ni foam substrate have been successfully obtained by a facile one-step hydrothermal method. The prepared products are functionalized as supercapacitor electrodes without adding any ancillary materials such as carbon black or binders. Their electrochemical properties show a high discharge areal capacitance (681 mF cm(-2) at 1 mA cm( 2)), good rate performance (495 mF cm(-2) at 5 mA cm(-2)) and long-term cycling stability (23.9% loss after 6000 repetitive cycles at 1 mA cm(-2)). Such excellent supercapacitive characteristics could be mainly attributed to their unique spatial structures which provide many active sites and enhance the combination between the electrode and Ni foam to support fast ion and electron transfer. In addition, the prepared alpha-Fe2O3 product is also used as a photocatalyst for the photocatalytic degradation of several harmful organic dyes under visible light illumination. By comparing the photocatalytic performance towards Congo red dye with other photocatalysts, it was observed that the prepared spinous alpha-Fe2O3 hierarchical structure exhibited superior photocatalytic performance. Finally, photocatalytic recycle tests showed the superiority of the prepared alpha-Fe2O3 product. This demonstrates that spinous alpha-Fe2O3 structures could be promising candidate materials for high-capacity, low-cost supercapacitor electrodes and environmentally friendly photocatalysts. PMID- 27005323 TI - Longer Ambulatory ECG Monitoring Increases Identification of Clinically Significant Ectopy. AB - BACKGROUND: Frequent premature ventricular contractions (PVCs) can cause a reversible reduction in systolic function. Most studies use 24-hour ambulatory electrocardiograms (AECGs) to assess PVC burden; however, PVC counts vary across 24-hour periods. We hypothesized that extended AECG monitoring would better identify clinically significant ectopy. METHODS: All 14-day AECGs performed at the San Francisco Veterans Affairs Medical Center between 2012 and 2015 (N = 694) were reviewed, and individuals with PVC counts >=1.0% of total heartbeats were included (N = 101). Daily PVC counts and the range of these values across 24-hour periods were assessed. Median time for these ranges to cross clinically significant thresholds (PVCs >= 10%, 15%, or 20% of total heartbeats) was determined. RESULTS: Median PVC burden was 2.6% of total heartbeats (interquartile range [IQR]: 1.6-5.4%) and the median range across 24-hour periods was 3.6% (IQR: 2.0-9.1%). Individual ranges of daily PVC burden crossed thresholds of 10%, 15%, and 20% of total heartbeats in 26.7%, 16.8%, and 6.9% of patients, respectively. Median time to detecting an individual's maximum PVC burden was 6 days (IQR: 2-11 days). While 75% of those who reached the 20% threshold did so on day one of monitoring, only 53% of those reaching the 10% threshold did similarly, with a continually increasing yield throughout the 14 day monitoring period. CONCLUSIONS: PVC burden varies widely from day-to-day. While most patients with PVC burdens >=20% were detected with 24 hours of monitoring, extended monitoring nearly doubled the identification of those reaching the 10% threshold. PMID- 27005321 TI - Unlocking the Potential of Purinergic Signaling in Transplantation. AB - Purinergic signaling has been recognized as playing an important role in inflammation, angiogenesis, malignancy, diabetes and neural transmission. Activation of signaling pathways downstream from purinergic receptors may also be implicated in transplantation and related vascular injury. Following transplantation, the proinflammatory "danger signal" adenosine triphosphate (ATP) is released from damaged cells and promotes proliferation and activation of a variety of immune cells. Targeting purinergic signaling pathways may promote immunosuppression and ameliorate inflammation. Under pathophysiological conditions, nucleotide-scavenging ectonucleotidases CD39 and CD73 hydrolyze ATP, ultimately, to the anti-inflammatory mediator adenosine. Adenosine suppresses proinflammatory cytokine production and is associated with improved graft survival and decreased severity of graft-versus-host disease. Furthermore, purinergic signaling is involved both directly and indirectly in the mechanism of action of several existing immunosuppressive drugs, such as calcineurin inhibitors and mammalian target of rapamycin inhibitors. Targeting of purinergic receptor pathways, particularly in the setting of combination therapies, could become a valuable immunosuppressive strategy in transplantation. This review focuses on the role of the purinergic signaling pathway in transplantation and immunosuppression and explores possible future applications in clinical practice. PMID- 27005324 TI - Coronary artery calcium score and N-terminal pro-B-type natriuretic peptide as potential gatekeepers for myocardial perfusion imaging. AB - Myocardial perfusion imaging (MPI) holds an important place as non-invasive risk assessment in patients with intermediate risk of coronary heart disease (CHD). However, as much as 60-70% of MPI scans are normal. This study evaluates the role of coronary artery calcium scoring (CAC score) and NT-proBNP as potential gatekeepers for MPI. Patients with intermediate risk of CHD referred for standard MPI were included. CAC score and NT-proBNP were both assessed at the day of the stress study. Sensitivity, specificity and NPV for prediction of abnormal MPI scans were calculated for CAC, NT-proBNP and the combination hereof. A total of 190 patients were included (mean age 61 +/- 12 years, 55% female) of whom 24% had known CHD. In all 30% of the scans were abnormal. CAC score achieved the highest AUC regardless of whether patients with known CHD were included or not [AUC 0.75 95% CI (0.66-0.84) and AUC 0.79 (0.68-0.91)]. As a singular variable, CAC score was the most potent predictor with a sensitivity of 85%, specificity of 39% and NPV 88%. The combination of CAC score<10 and NT-proBNP>26 reached a sensitivity of 98% and NPV 94%, where 8% of scans tentatively could be avoided. In patients referred for MPI with intermediate risk for CHD, a combination of CAC score and NT-proBNP could be used to identify a group of patients where MPI could be averted with a high degree of diagnostic safety. PMID- 27005325 TI - Diverse fission yeast genes required for responding to oxidative and metal stress: Comparative analysis of glutathione-related and other defense gene deletions. AB - Living organisms have evolved multiple sophisticated mechanisms to deal with reactive oxygen species. We constructed a collection of twelve single-gene deletion strains of the fission yeast Schizosaccharomyces pombe designed for the study of oxidative and heavy metal stress responses. This collection contains deletions of biosynthetic enzymes of glutathione (Deltagcs1 and Deltagsa1), phytochelatin (Deltapcs2), ubiquinone (Deltaabc1) and ergothioneine (Deltaegt1), as well as catalase (Deltactt1), thioredoxins (Deltatrx1 and Deltatrx2), Cu/Zn- and Mn- superoxide dismutases (SODs; Deltasod1 and Deltasod2), sulfiredoxin (Deltasrx1) and sulfide-quinone oxidoreductase (Deltahmt2). First, we employed metabolomic analysis to examine the mutants of the glutathione biosynthetic pathway. We found that ophthalmic acid was produced by the same enzymes as glutathione in S. pombe. The identical genetic background of the strains allowed us to assess the severity of the individual gene knockouts by treating the deletion strains with oxidative agents. Among other results, we found that glutathione deletion strains were not particularly sensitive to peroxide or superoxide, but highly sensitive to cadmium stress. Our results show the astonishing diversity in cellular adaptation mechanisms to various types of oxidative and metal stress and provide a useful tool for further research into stress responses. PMID- 27005326 TI - The CD4/CD8 Ratio is Inversely Associated with Carotid Intima-Media Thickness Progression in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Treatment. AB - Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 +/- 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc, and 2 (2.08%) just with nucleoside reverse transcriptase inhibitors. The mean of ART exposition was 6.9 +/- 5.9 years. Twenty six (27%) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) were hypertensive, 4 (4.16%) had type 2 diabetes, 23 (23.9%) had dyslipidemia, and 31 (32.3%) were infected with hepatitis C virus. Baseline cIMT was significantly associated with age (rho = 0.497; p < .001), basal glucemia (rho = 0.323; p = .001), triglycerides (rho = 0.232; p = .023), Framingham risk score (rho = 0.324; p = .001), CD4/CD8 ratio (rho = -0.176; p = .05), and dyslipidemia (0.72 +/- 0.16 mm vs. 0.63 +/- 0.11 mm; p = .029). In multivariable analysis where cardiovascular risk factor and ART were included, cIMT progression was inversely associated with CD4/CD8 ratio [odds ratio (OR) = 0.283; confidence interval (95% CI) 0.099-0.809; p = .019]. In conclusion, the inversion of CD4/CD8 ratio in treated HIV-infected patients is independently associated with cIMT progression, a marker of coronary heart disease. Therefore, it might be clinically useful as predictor of cardiovascular events. PMID- 27005327 TI - Tuning the photophysical properties of 4'-substituted terpyridines - an experimental and theoretical study. AB - Several 2,2':6',2''-terpyridines substituted in the 4'-position were synthesized and their photophysical properties were investigated by absorption and photoluminescence spectroscopy in dilute solutions and solid state. The studies confirmed that the absorption and emission wavelengths, fluorescence quantum yields and lifetimes of 1-R(1-16) are strongly structure-related, demonstrating a decisive role of the nature of the substituent in determining the photophysical properties of 4'-functionalized terpyridines. Additionally, the density functional theory (DFT) calculations were performed for 1-R(1-16) to get insight into their electronic structure and spectroscopic properties. PMID- 27005328 TI - High Diversity Revealed in Leaf-Associated Protists (Rhizaria: Cercozoa) of Brassicaceae. AB - The largest biological surface on earth is formed by plant leaves. These leaf surfaces are colonized by a specialized suite of leaf-inhabiting microorganisms, recently termed "phyllosphere microbiome". Microbial prey, however, attract microbial predators. Protists in particular have been shown to structure bacterial communities on plant surfaces, but virtually nothing is known about the community composition of protists on leaves. Using newly designed specific primers targeting the 18S rDNA gene of Cercozoa, we investigated the species richness of this common protist group on leaves of four Brassicaceae species from two different locations in a cloning-based approach. The generated sequences revealed a broad diversity of leaf-associated Cercozoa, mostly bacterial feeders, but also including known plant pathogens and a taxon of potential endophytes that were recently described as algal predators in freshwater systems. This initial study shows that protists must be regarded as an integral part of the microbial diversity in the phyllosphere of plants. PMID- 27005330 TI - Patterning of sub-50 nm perpendicular CoFeB/MgO-based magnetic tunnel junctions. AB - Perpendicular magnetic tunnel junctions (p-MTJs) were patterned into nanopillars using electron-beam lithography to study their scaling and switching behaviour. Magnetoresistance measurements of annealed and unannealed p-MTJ films using scanning probe microscopy showed good agreement with Monte Carlo modeling. p-MTJ pillars demonstrated clear parallel magnetic states, both 'up' or both 'down' following AC-demagnetization. Significant variability in the resistance of p-MTJ pillars was observed and attributed to edge features generated during patterning or local inhomogeneity in the MgO layer. PMID- 27005329 TI - Effects of environmental radiation on testes and spermatogenesis in wild large Japanese field mice (Apodemus speciosus) from Fukushima. AB - The Fukushima Daiichi Nuclear Power Plant (FDNPP) accident that occurred after the Great East Japan Earthquake in March 2011 released large quantities of radionuclides to the environment. The long-term effects of radioactive cesium (Cs) on biota are of particular concern. We investigated the accumulation of radioactive Cs derived from the FDNPP accident, and chronic effects of environmental radionuclides on male reproduction, in the large Japanese field mouse (Apodemus speciosus). In 2013 and 2014, wild mice were captured at 2 sites in Fukushima Prefecture and at 2 control sites that were distant from Fukushima. Although the median concentrations of (134)Cs and (137)Cs in the mice from Fukushima exceeded 4,000 Bq/kg, there were no significant differences in the apoptotic cell frequencies or the frequencies of morphologically abnormal sperm among the capture sites. Thus, we conclude that radiation did not cause substantial male subfertility in Fukushima during 2013 and 2014, and radionuclide pollution levels in the study sites would not be detrimental to spermatogenesis of the wild mice in Fukushima. PMID- 27005331 TI - [Vitamin D, falls and fractures in older adults: chronicle of a paradigm shift]. PMID- 27005332 TI - [Epidemiology of vitamin-D deficiency]. AB - The 25-hydroxyvitamin D (25OHD) serum concentration is the consensual marker of vitamin D status. In the general population, the Institute of Medicine considers that a 25OHD level >20 ng/mL is sufficient for bone health in most subjects. In osteoporosis patients, in those who have a pathology or who receive drugs that may increase the risk of osteoporosis, as well as in patients with chronic kidney disease, many experts think that an optimal vitamin D status is better defined by a 25OHD concentration >30 ng/mL. In the French general population, 43-50% of subjects have a 25OHD level <20 ng/mL and approximately 80% have a 25OHD <30 ng/mL. In chronic diseased patients, as well as in some categories of the general population such as elderly people, the percentage of subjects with a 25OHD level below 20 ng/mL is frequently well above 50%. Epidemiologic studies allow us to identify risk factors for vitamin D deficiency such as ageing, overweight, dark skin pigmentation, wearing covering clothes, or having a low level of outdoor activity. This will help to target vitamin D supplementation to "at-risk" subjects. However, discussions on means to improve the vitamin D status of the overall population such as allowing higher levels of food fortification, are needed. PMID- 27005333 TI - [Prevention of impaired mobility in the elderly in primary care: a brief report]. AB - The loss autonomy in the aging population is a major public health issue. Mobility impairment, which precedes loss of autonomy, could yet be accessible to multi-modal and personalised programs to enhance balance and physical performances, and avoid loss of autonomy. Moreover, such preventive programs are likely to be more effective when the patients are taken in charge before presenting with difficulties in daily living. The aging demographics and the consequences of the loss of autonomy clearly indicate a need for better addressing these patients with lowering mobility, even though they will mostly have subtle symptoms and no spontaneous complaints. This could be achieved by improving the screening of mobility impairment and the development of specific personalised preventive programs in primary care. In this brief narrative review, we aimed to summarise the current body of knowledge on mobility impairment prevention in the elderly, and open the field for future research in primary care. PMID- 27005334 TI - [Difficulties encountered by the general practitioner in the management of the elderly people in complex medical and psycho-social condition: role of mobile teams]. AB - OBJECTIVE: Assessed the difficulties encountered by general practitioners in the care of the elderly with complex medical and psycho-social conditions, their knowledge of the geriatric network, the interest engendered by setting-up mobile community based geriatric units. METHODS: The survey was both qualitative and quantitative and took the form of a telephone interview and a multimodal questionnaire (telephone interview, postal or email questionnaire) of general practitioners in the areas of Annecy, Grenoble and Roanne (France). RESULTS: Sixty five per cent of the 129 GPs contacted by telephone said the survey interested them. One hundred and eleven physicians replied to the questionnaire. The first priority for intervention of the mobile geriatric unit should be the management of the elderly with cognitive disorders and behavioural symptoms (43 replies) that pose the most problems for physicians. The mobile team should be available, and easy to contact rapidly. The request for intervention should be made by the GP (69 replies, 72.6%), by telephone (95 replies, 86%) and the visit made within the following 48 - 72 hours (60 replies, 67.4%). DISCUSSION: Our results confirm the existence of difficulties in the care the elderly people with complex conditions that justify experimentation of community mobile geriatric teams. PMID- 27005335 TI - [About the HbA1c in the elderly]. AB - HbA1c product of non enzymatic glycation of HbA increases in relation with the mean blood glucose level during the former 2-3 months. HbA1c levels are correlated with the development of diabetic complications and HbA1c assessment is now the gold standard for evaluation of diabetes control. HbA1c level should not be higher than 7% to avoid these complications. However, in aged peoples, the objectives of diabetes control vary according to their health status. It must be good with HbA1c lower than 7-7.5% in healthy subjects and more relax in subjects with symptoms of frailty and risks of non perceived and self corrected hypoglycemia. Under these conditions, HbA1c values lower than 8 to 9% are advised. Nevertheless, hypoglycemia episodes may occur in patients with high HbA1c and capillary glucose follow-up is necessary for detection of such complications. PMID- 27005336 TI - [External validation of the short emergency geriatric assessment (SEGA) instrument on the SAFES cohort]. AB - The aim of the study was to achieve the external validation of the SAGA instrument on the SAFES cohort. This was a prospective longitudinal multicentre cohort study, including patients aged 75 years or over, hospitalized in a short stay medical ward via emergency department. A comprehensive geriatric assessment was implemented. The psychometric validation enabled the study of feasibility, internal consistency, convergent, discriminant, and predictive validity of the instrument. The 1 306 patients of the cohort was 85+/-6 years, with a majority of women (65%). The completion rate of the SEGA instrument was 94%. Internal consistency was good (Cronbach alpha coefficient=0.7). Convergent validity was poor: Donini instrument (kappa=0.18; IC 95%=0.13-0.23), Rockwood instrument (kappa=0.04; IC 95%=0.02-0.06), and Winograd instrument (kappa=0.04; IC 95%=0.01 0.07). The ability of the instrument to discriminate clinically different groups was good. The SEGA instrument predicted well one-year mortality as well as one year institution admission. Despite poor convergent validity (which is classic with frailty tools, SEGA instrument has satisfactory metrological properties, allowing its use in emergency departments and immediate post-emergency circumstances. PMID- 27005337 TI - [Episodic foresight in normal cognitive and pathological aging]. AB - The ability to project the self forward in time to pre-experience personal events is referred to as episodic future thinking. Different theories have been proposed to try to explain the neurocognitive mechanisms underlying episodic future thinking. In this paper we focus on studies concerning the episodic prospection capacity in cognitive aging and in neurodegenerative diseases such as Alzheimer's disease and semantic dementia. Older adults usually produce fewer episodic details than young adults when recalling past events and when imagining future events. Patients with early to moderate Alzheimer's disease have impaired capacity in the generation of episodic details for retrieved past events and imagined future events. Similarly patients with early to moderate semantic dementia have difficulties in episodic future thinking whereas they succeed to retrieve episodic past events. These patterns are discussed with regard to the respective role of the episodic and personal semantic representations in future personal thoughts as a function of temporal distance by purposing a new neurocognitive model (TEDIFT). PMID- 27005338 TI - [Exhaustion of family caregivers: a masked domestic crisis? A psychodynamic and systemic approach]. AB - We try, from our clinical practice in a geriatric medicine department, to identify the processes involved in family crisis, especially in the relationship carer/cared. Psychodynamic and systemic determinants are highlighted to understand how family caregivers may suffer burn out, and suggest preventive measures. PMID- 27005339 TI - [Normal aging of frontal lobe functions]. AB - Normal aging in individuals is often associated with morphological, metabolic and cognitive changes, which particularly concern the cerebral frontal regions. Starting from the "frontal lobe hypothesis of cognitive aging" (West, 1996), the present review is based on the neuroanatomical model developed by Stuss (2008), introducing four categories of frontal lobe functions: executive control, behavioural and emotional self-regulation and decision-making, energization and meta-cognitive functions. The selected studies only address the changes of one at least of these functions. The results suggest a deterioration of several cognitive frontal abilities in normal aging: flexibility, inhibition, planning, verbal fluency, implicit decision-making, second-order and affective theory of mind. Normal aging seems also to be characterised by a general reduction in processing speed observed during neuropsychological assessment (Salthouse, 1996). Nevertheless many cognitive functions remain preserved such as automatic or non conscious inhibition, specific capacities of flexibility and first-order theory of mind. Therefore normal aging doesn't seem to be associated with a global cognitive decline but rather with a selective change in some frontal systems, conclusion which should be taken into account for designing caring programs in normal aging. PMID- 27005340 TI - [Alzheimer's disease and Helicobacter pylori infection: a possible link?]. AB - Alzheimer's disease (AD) is associated with Abeta peptide and Tau protein deposits, but the initial process inducing the disease and ultimately neurodegeneration has not yet been elucidated. An infectious hypothesis is suggested by the alteration of the blood-brain barrier and the activation of neuroinflammation in the brain, which could play a role, especially in the decrease of Abeta peptide clearance. Several viral or bacterial agents have been incriminated, including Helicobacter pylori. Infection by H. pylori is acquired during childhood and often lifetime persisting, inducing a chronic gastric inflammation, which remains asymptomatic in approximately 80% of cases. However H. pylori infection can induce systemic inflammation and increase homocysteine levels, contributing to worsen AD lesions. Association between H. pylori and AD is suggested by 1) epidemiologic studies, which show higher AD prevalence and more pronounced cognitive impairment in infected than in non-infected subjects; 2) experimental studies in murine models: a) in a first study we evaluated the impact of H. pylori infection on the brain of non-AD predisposed C57BL/6J mice. After an 18-month infection, H. pylori induced a significant gastric inflammation but no brain Abeta deposit nor increased neuroinflammation was observed in their brain; b) we currently study the impact of Helicobacter species infection on behavior and cerebral lesions of AD transgenic (APPswe/PS1dE9) mice and their wild type littermate. The results of these studies do not allow to conclude a significant association between AD and H. pylory infection but may contribute to a better understanding of the role of brain neuroinflammation in AD. PMID- 27005341 TI - [Neuropsychology of humor: an introduction Part 1. Psychological data]. AB - Humor is, from a psychological point of view, a complex process involving cognitive, affective, interspersonal and social elements in a interpersonal context. Its cognitive core is based on the perception of incongruity between two related inconsistent or contradictory mental representations. The total or partial resolution of incongruity in a playful frame is associated with a specific positive emotion, which characteristics and intensity are determined by the structure of the humoristic stimulus more than its content, and the personal and social contexts. Main theories of humor are reviewed as well as its development, its cognitive and affective correlates, and the influence of genre, age and personality. PMID- 27005342 TI - [Evaluation of psychosocial interventions for dementia: what to learn from the Cochrane Library?]. AB - Psychosocial interventions for people with dementia have expanded in the last decades, and have been subject to an important number of evaluation attempts that often lead to scientifically flaw results. To study these failures we analysed the meta-analyses of the Cochrane Library. Among 18 meta-analyses, 11 were selected for the purpose of this study. These papers were analysed on the basis of the Cochrane selection criteria, methodological quality and biases, principal outcomes and implication for practice and research. Results are discussed and analysed according to the clinical practice and scientific literature of the matter of concern. Main outcomes of this review point that: (1) it is necessary to adopt an investigation methodology adapted to specific characteristics of psychosocial interventions; (2) methodological weaknesses of randomised control trials are prejudicial to quality of research and clinical practice; (3) implementation of randomised control trials call for necessary fundamental prerequisites; and (4) other research methods than randomised control trials are susceptible to give as much, if not more, informative results. A research and practice implementation strategy is suggested. PMID- 27005345 TI - ANZSRS Oral Presentations. PMID- 27005344 TI - New Investigators Awards - ANZSRS Oral Presentations. PMID- 27005347 TI - Nurses SIG Symposium Part 1 Oral Presentations. PMID- 27005346 TI - ANZSRS Poster Presentations. PMID- 27005348 TI - Nurses SIG Symposium Part 2 Oral Presentations. PMID- 27005349 TI - Chronic Obstructive Pulmonary Disease 1 Oral Presentations. PMID- 27005350 TI - Primary Care 1 Oral Presentations. PMID- 27005352 TI - Asthma and Allergy 1 Oral Presentations. PMID- 27005351 TI - Cell Biology/Immunology 1 Oral Presentations. PMID- 27005353 TI - Cell Biology/Immunology 2 Oral Presentations. PMID- 27005354 TI - Paediatric 1 Oral Presentations. PMID- 27005355 TI - Tobacco and Related Substances Oral Presentations. PMID- 27005356 TI - TSANZ Ann Woolcock Young Investigator Awards Oral Presentations. PMID- 27005357 TI - Evidence-Based Medicine and Practice Oral Presentations. PMID- 27005358 TI - Lung Cancer 1 Oral Presentations. PMID- 27005359 TI - Paediatric 2 Oral Presentations. PMID- 27005361 TI - Respiratory Infectious Diseases 1 Oral Presentations. PMID- 27005360 TI - Asthma 2 Oral Presentations. PMID- 27005362 TI - Chronic Obstructive Pulmonary Disease 2 Oral Presentations. PMID- 27005363 TI - Cystic Fibrosis Oral Presentations. PMID- 27005364 TI - OLIV 1 Oral Presentations. PMID- 27005365 TI - Interventional Pulmonary/Bronchology 1 Oral Presentations. PMID- 27005366 TI - Asthma and Allergy 3 Oral Presentations. PMID- 27005367 TI - Physiology and Sleep 1 Oral Presentations. PMID- 27005368 TI - Chronic Obstructive Pulmonary Disease 3 Oral Presentations. PMID- 27005369 TI - Respiratory Infectious Diseases 2 Oral Presentations. PMID- 27005370 TI - Interventional Pulmonary/Bronchology 2 Oral Presentations. PMID- 27005371 TI - Physiology and Sleep 2 Oral Presentations. PMID- 27005372 TI - OLIV 2 Oral Presentations. PMID- 27005373 TI - Asthma and Allergy 4 Oral Presentations. PMID- 27005374 TI - Occupational & Environmental Lung Disease/Population Health Oral Presentations. PMID- 27005376 TI - Asthma and Allergy SIG 1 Poster Presentations. PMID- 27005375 TI - Lung Cancer 2 Oral Presentations. PMID- 27005378 TI - Asthma and Allergy SIG 3 Poster Presentations. PMID- 27005377 TI - Asthma and Allergy SIG 2 Poster Presentations. PMID- 27005379 TI - Chronic Obstructive Pulmonary Disease SIG 1 Poster Presentations. PMID- 27005380 TI - Cell Biology / Immunology SIG Poster Presentations. PMID- 27005381 TI - Chronic Obstructive Pulmonary Disease SIG 2 Poster Presentations. PMID- 27005383 TI - Asthma and Allergy SIG 1 Poster Presentations. PMID- 27005382 TI - Chronic Obstructive Pulmonary Disease SIG 3 Poster Presentations. PMID- 27005385 TI - Interventional Pulmonary/Bronchology SIG 2 Poster Presentations. PMID- 27005384 TI - Evidence-Based Medicine and Practice SIG Poster Presentations. PMID- 27005386 TI - Interventional Pulmonary/Bronchology SIG 1 Poster Presentations. PMID- 27005387 TI - Lung Cancer SIG Poster Presentations. PMID- 27005388 TI - Respiratory Infectious Diseases SIG Poster Presentations. PMID- 27005389 TI - Cystic Fibrosis SIG Poster Presentations. PMID- 27005390 TI - Physiology and Sleep SIG Poster Presentations. PMID- 27005391 TI - Occupational & Environmental Lung Disease/Population Health SIG Poster Presentations. PMID- 27005392 TI - Paediatric SIG Poster Presentations. PMID- 27005394 TI - Sponsors Page. PMID- 27005395 TI - Diagnosing autism spectrum disorder (ASD) among adults. PMID- 27005396 TI - Community engagement practices in Southern Africa: Review and thematic synthesis of studies done in Botswana, Zimbabwe and South Africa. AB - Community Engagement (CE) is intended to enhance the participation of community stakeholders in research. CE is usually mentioned in publications as researchers discuss how they carried out community entry, consent and retained study participants but the actual CE activities are not always well documented. This paper reviews CE strategies employed in health research in Botswana, South Africa and Zimbabwe with reference to the development of a CE strategy for a multi centre study to be conducted in these countries. The search was conducted using JANE (Journal/Author Name Estimator), Google Scholar and PubMed with known institutions and researchers providing context-specific material. The final synthesis includes 35 publications, 2 reports and 2 abstracts. There is evidence of CE being practiced in health research and eight closely related CE strategies were revealed. We conclude that since communities are heterogeneous and unique, CE activities will not have similar results in different settings. Even though there was insufficient evidence to determine which CE strategy is most effective, the review provides sufficient information to develop a CE strategy for a multi centre study using the various strategies and activities described. PMID- 27005397 TI - Praziquantel induced oxidative stress and apoptosis-like cell death in Raillietina echinobothrida. AB - Praziquantel (PZQ) is an anthelmintic drug used against trematode and cestode parasites of humans and veterinary animals. Since praziquantel was introduced as a broadspectrum anthelmintic, numerous studies described its successful use against helminth parasites, but its exact mechanism of action is feebly understood. Therefore, the present study was carried out to evaluate the possible role of PZQ induced oxidative stress in apoptosis-like cell death in the poultry tapeworm Raillietina echinobothrida. Parasite viability assay revealed a time dependent reduction in the worm viability compared to the control. Transmission electron microscopy showed typical apoptotic features like condensed nucleus, damaged nuclear envelope and altered mitochondrial membrane in PZQ exposed parasites. Results revealed chromatin condensation and DNA fragmentation in PZQ exposed parasites. There was a notable decline in the level of glutathione and glutathione-s-transferase activity leading to the augmented generation of reactive oxygen species. This led to the alterations in the mitochondrial membrane potential with increased active caspase-3/7, confirms the involvement of mitochondria in the event. The present study suggests that PZQ exerts oxidative stress leading to apoptosis-like events in the parasites resulting their death. PMID- 27005398 TI - Magnetic Sensing through the Abdomen of the Honey bee. AB - Honey bees have the ability to detect the Earth's magnetic field, and the suspected magnetoreceptors are the iron granules in the abdomens of the bees. To identify the sensing route of honey bee magnetoreception, we conducted a classical conditioning experiment in which the responses of the proboscis extension reflex (PER) were monitored. Honey bees were successfully trained to associate the magnetic stimulus with a sucrose reward after two days of training. When the neural connection of the ventral nerve cord (VNC) between the abdomen and the thorax was cut, the honey bees no longer associated the magnetic stimulus with the sucrose reward but still responded to an olfactory PER task. The neural responses elicited in response to the change of magnetic field were also recorded at the VNC. Our results suggest that the honey bee is a new model animal for the investigation of magnetite-based magnetoreception. PMID- 27005399 TI - Bench-stable frustrated Lewis pair chemistry: fluoroborate salts as precatalysts for the C-H borylation of heteroarenes. AB - While the organotrifluoroborate group is commonly used as a leaving group in cross-coupling reactions, we now show that their high stability can be used to protect the Lewis acidic moieties of frustrated Lewis pair catalysts. Indeed, the air and moisture-stable trifluoro- and difluoroborate derivatives of bulky (tetramethylpiperidino)benzene are shown to be conveniently converted to their dihydroborane analogue which is known to activate small molecules. An efficient synthesis route to these stable and convenient precatalysts, their deprotection chemistry and their benchtop use for the dehydrogenative borylation of heteroarenes is presented. PMID- 27005400 TI - A theory-based approach to nursing shared governance. AB - BACKGROUND: The discipline of nursing uses a general definition of shared governance. The discipline's lack of a specified theory with precepts and propositions contributes to persistent barriers in progress toward building evidence-based knowledge through systematic study. PURPOSE: The purposes of this article were to describe the development and elements of a program theory approach for nursing shared governance implementation and to recommend further testing. METHOD: Five studies using multiple methods are described using a structured framework. The studies led to the use of Lipsey's method of theory development for program implementation to develop a theory for shared governance for nursing. DISCUSSION: Nine competencies were verified to define nursing practice council effectiveness. Other findings reveal that nurse empowerment results from alignment between the competencies of self- directed work teams and the competencies of organizational leaders. Implementation of GEMS theory based nursing shared governance can advance goals at the individual, unit, department, and organization level. CONCLUSION: Advancing professional nursing practice requires that nursing concepts are systematically studied and then formalized for implementation. This article describes the development of a theoretical foundation for the systematic study and implementation of nursing shared governance. PMID- 27005401 TI - Transcriptome analyses reveal molecular mechanism underlying tapping panel dryness of rubber tree (Hevea brasiliensis). AB - Tapping panel dryness (TPD) is a serious threat to natural rubber yields from rubber trees, but the molecular mechanisms underlying TPD remain poorly understood. To identify TPD-related genes and reveal these molecular mechanisms, we sequenced and compared the transcriptomes of bark between healthy and TPD trees. In total, 57,760 assembled genes were obtained and analyzed in details. In contrast to healthy rubber trees, 5652 and 2485 genes were up- or downregulated, respectively, in TPD trees. The TPD-related genes were significantly enriched in eight GO terms and five KEGG pathways and were closely associated with ROS metabolism, programmed cell death and rubber biosynthesis. Our results suggest that rubber tree TPD is a complex process involving many genes. The observed lower rubber yield from TPD trees might result from lower isopentenyl diphosphate (IPP) available for rubber biosynthesis and from downregulation of the genes in post-IPP steps of rubber biosynthesis pathway. Our results not only extend our understanding of the complex molecular events involved in TPD but also will be useful for developing effective measures to control TPD of rubber trees. PMID- 27005402 TI - Measure development and assessing outcomes in palliative care: Always look on the bright side of life.... PMID- 27005403 TI - The path. PMID- 27005404 TI - Sex differences in the rate of abdominal adipose accrual during adulthood: the Fels Longitudinal Study. AB - OBJECTIVES: The purpose of this analysis was to evaluate sex differences in the rate of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) accrual in adults. Secondary analyses examined differences in the rate of VAT and SAT accrual in premenopausal, perimenopausal and postmenopausal women. SUBJECTS/METHODS: Participants were 472 (60% female) non-Hispanic whites and aged 18-84 years at baseline in whom abdominal VAT and SAT were assessed using multiple-image magnetic resonance imaging at two time points, with an average follow-up of 7.3+/-2.6 years. Linear regression models were used to examine the effects of sex, baseline age and their interaction on rate of change per year in body composition measures (DeltaBMI, DeltaVAT and DeltaVAT/SAT ratio (DeltaVSR)) independent of baseline body composition measures, visit year, income, marital status, physical activity, smoking and alcohol intake. Secondary analyses examined differences in the rate of fat change by menopausal status (premenopausal, perimenopausal, postmenopausal). RESULTS: Levels of body mass index (BMI), VAT and VSR all increased over the 7-year period on average (P<0.001); however, the change in BMI (mean DeltaBMI=+0.5%) was far smaller than for VAT (mean DeltaVAT=+6.8%), SAT (mean DeltaSAT=+2.4%) and VSR (mean DeltaVSR=+3.6%). DeltaBMI, DeltaVAT and DeltaSAT decreased linearly with age in both sexes (P<0.01), such that older individuals had lower rates of BMI, VAT and SAT gain, and this deceleration in BMI, VAT and SAT accrual was greater in men than women (P for interaction <0.05). DeltaVSR did not vary with age in either sex but remained higher in men than women throughout adulthood. There were no differences in rate of weight or fat gain by menopausal status after adjustment for age. CONCLUSIONS: Men and women continue to accrue abdominal adiposity with age, but the rate of weight and fat gain decreases over time, particularly in men. PMID- 27005405 TI - Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. AB - BACKGROUND: Obesity is strongly associated with prevalence of obstructive sleep apnea (OSA), and weight loss has been shown to reduce disease severity. OBJECTIVE: To investigate whether liraglutide 3.0 mg reduces OSA severity compared with placebo using the primary end point of change in apnea-hypopnea index (AHI) after 32 weeks. Liraglutide's weight loss efficacy was also examined. SUBJECTS/METHODS: In this randomized, double-blind trial, non-diabetic participants with obesity who had moderate (AHI 15-29.9 events h(-1)) or severe (AHI ?30 events h(-1)) OSA and were unwilling/unable to use continuous positive airway pressure therapy were randomized for 32 weeks to liraglutide 3.0 mg (n=180) or placebo (n=179), both as adjunct to diet (500 kcal day(-1) deficit) and exercise. Baseline characteristics were similar between groups (mean age 48.5 years, males 71.9%, AHI 49.2 events h(-1), severe OSA 67.1%, body weight 117.6 kg, body mass index 39.1 kg m(-2), prediabetes 63.2%, HbA1c 5.7%). RESULTS: After 32 weeks, the mean reduction in AHI was greater with liraglutide than with placebo (-12.2 vs -6.1 events h(-1), estimated treatment difference: -6.1 events h(-1) (95% confidence interval (CI), -11.0 to -1.2), P=0.0150). Liraglutide produced greater mean percentage weight loss compared with placebo (-5.7% vs 1.6%, estimated treatment difference: -4.2% (95% CI, -5.2 to -3.1%), P<0.0001). A statistically significant association between the degree of weight loss and improvement in OSA end points (P<0.01, all) was demonstrated post hoc. Greater reductions in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) were seen with liraglutide versus placebo (both P<0.001). The safety profile of liraglutide 3.0 mg was similar to that seen with doses ?1.8 mg. CONCLUSIONS: As an adjunct to diet and exercise, liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, SBP and HbA1c in participants with obesity and moderate/severe OSA. The results confirm that weight loss improves OSA-related parameters. PMID- 27005406 TI - Pirfenidone-induced severe phototoxic reaction in a patient with idiopathic lung fibrosis. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disease with an estimated 5-year survival of approximately 20%. Pirfenidone is a novel orally available antifibrotic agent that reduces disease progression and improves survival of patients with IPF. The most common adverse effects of pirfenidone include gastrointestinal symptoms, hepatic dysfunction or skin photosensitivity and rash. A 64-year-old male patient presented in our clinic with a strong generalized exfoliative erythema and intense itching accompanied by fatigue and mild fever after a mild sun exposure for 5 days during holidays in Turkey. The patient had been diagnosed with IPF 2 months ago and 1 month later he started a therapy with pirfenidone with good tolerability. OBJECTIVE: In this report, we noted a severe phototoxic reaction under treatment with pirfenidone which underlies the potential phototoxic effect of this drug besides the already reported photosensitivity. METHODS: Routine laboratory tests and a skin biopsy were performed. RESULTS: Laboratory tests indicated increased markers of inflammation. The skin biopsy showed a perivascular lymphocytic inflammatory infiltrate, ballooning of keratinocytes with increased apoptosis. These findings were most consistent with a severe phototoxic reaction to pirfenidone which had been directly discontinued. The patient was started on oral methylprednisolone 100 mg/day which was gradually tapered off along with topical corticosteroids (mometasone furoate 0.1% cream) and oral antihistamines. This treatment led to a slow but complete resolution of the skin lesions within 20 days. CONCLUSION: To our knowledge, this is the first reported case of a severe phototoxic reaction during treatment with pirfenidone. Our aim by presenting this case is to increase the awareness of clinicians for severe phototoxic effects of oral pirfenidone. PMID- 27005407 TI - Can emergency nurses safely and accurately remove cervical spine collars in low risk adult trauma patients: An integrative review. AB - BACKGROUND: Well validated clinical decision rules exist to facilitate the safe removal of collars in the alert, orientated, low risk adult trauma patient, however this practice is traditionally conducted by medical staff. The aim of this review is to synthesise current evidence to determine the efficacy of emergency nurses in safely and accurately removing cervical spine collars using cervical spine rules, in alert, orientated, low risk trauma adult patients. METHODS: A multi-method search strategy was used to find primary research studies followed by a rigorous screening and quality appraisal process. Data from included articles were extracted, grouped and synthesised. RESULTS: Nine quantitative research articles resulted in four key findings: the inter-rater reliability between nurses and doctors clearing the cervical spine was high (kappa range (0.61-0.80)); nurses can safely implement the cervical spine clinical decision rule; use of a cervical spine clinical decision rule decreases the time patients are immobilised and; nurses felt confident applying a cervical spine clinical decision rule. CONCLUSION: Appropriately trained emergency nurses can safely apply cervical spine rules to alert, orientated, low risk adult trauma patients. Implementation of nurses clearing cervical spines should include training and ongoing monitoring. PMID- 27005408 TI - Down with food waste. PMID- 27005409 TI - Sensitive determination of three aconitum alkaloids and their metabolites in human plasma by matrix solid-phase dispersion with vortex-assisted dispersive liquid-liquid microextraction and HPLC with diode array detection. AB - A simple and sensitive method for determination of three aconitum alkaloids and their metabolites in human plasma was developed using matrix solid-phase dispersion combined with vortex-assisted dispersive liquid-liquid microextraction and high-performance liquid chromatography with diode array detection. The plasma sample was directly purified by matrix solid-phase dispersion and the eluate obtained was concentrated and further clarified by vortex-assisted dispersive liquid-liquid microextraction. Some important parameters affecting the extraction efficiency, such as type and amount of dispersing sorbent, type and volume of elution solvent, type and volume of extraction solvent, salt concentration as well as sample solution pH, were investigated in detail. Under optimal conditions, the proposed method has good repeatability and reproducibility with intraday and interday relative standard deviations lower than 5.44 and 5.75%, respectively. The recoveries of the aconitum alkaloids ranged from 73.81 to 101.82%, and the detection limits were achieved within the range of 1.6-2.1 ng/mL. The proposed method offered the advantages of good applicability, sensitivity, simplicity, and feasibility, which makes it suitable for the determination of trace amounts of aconitum alkaloids in human plasma samples. PMID- 27005410 TI - Smart Electronic Textiles. AB - This Review describes the state-of-the-art of wearable electronics (smart textiles). The unique and promising advantages of smart electronic textiles are highlighted by comparing them with the conventional planar counterparts. The main kinds of smart electronic textiles based on different functionalities, namely the generation, storage, and utilization of electricity, are then discussed with an emphasis on the use of functional materials. The remaining challenges are summarized together with important new directions to provide some useful clues for the future development of smart electronic textiles. PMID- 27005411 TI - The metabolism and biotechnological application of betaine in microorganism. AB - Glycine betaine (betaine) is widely distributed in nature and can be found in many microorganisms, including bacteria, archaea, and fungi. Due to its particular functions, many microorganisms utilize betaine as a functional chemical and have evolved different metabolic pathways for the biosynthesis and catabolism of betaine. As in animals and plants, the principle role of betaine is to protect microbial cells against drought, osmotic stress, and temperature stress. In addition, the role of betaine in methyl group metabolism has been observed in a variety of microorganisms. Recent studies have shown that betaine supplementation can improve the performance of microbial strains used for the fermentation of lactate, ethanol, lysine, pyruvate, and vitamin B12, during which betaine can act as stress protectant or methyl donor for the biosynthesis of structurally complex compounds. In this review, we summarize the transport, synthesis, catabolism, and functions of betaine in microorganisms and discuss potential engineering strategies that employ betaine as a methyl donor for the biosynthesis of complex secondary metabolites such as a variety of vitamins, coenzymes, and antibiotics. In conclusion, the biocompatibility, C/N ratio, abundance, and comprehensive metabolic information of betaine collectively indicate that this molecule has great potential for broad applications in microbial biotechnology. PMID- 27005412 TI - Melatonin production in Escherichia coli by dual expression of serotonin N acetyltransferase and caffeic acid O-methyltransferase. AB - Melatonin is a well-known bioactive molecule produced in animals and plants and a well-studied natural compound. Two enzymatic steps are required for the biosynthesis of melatonin from serotonin. First, serotonin N-acetyltransferase (SNAT) catalyzes serotonin to N-acetylserotonin (NAS) followed by the action of N acetylserotonin O-methyltransferase (ASMT), resulting in the synthesis of O methylated NAS, also known as melatonin. Attempts to document melatonin production in Escherichia coli have been unsuccessful to date due to either low enzyme activity or inactive ASMT expression. Here, we employed caffeic acid O methyltransferase (COMT) instead of ASMT, as COMT is a multifunctional enzyme that has ASMT activity as well. Among several combinations of dual expression cassettes, recombinant E. coli that expressed sheep SNAT with rice COMT produced a high quantity of melatonin, which was measured in a culture medium (1.46 mg/L in response to 1 mM serotonin). This level was several orders of magnitude higher than that produced in transgenic rice and tomato overexpressing sheep SNAT and ASMT, respectively. This heterologous expression system can be widely employed to screen various putative SNAT or ASMT genes from animals and plants as well as to overproduce melatonin in various useful microorganisms. PMID- 27005413 TI - Direct in situ butanol recovery inside the packed bed during continuous acetone butanol-ethanol (ABE) fermentation. AB - In this study, the integrated in situ extraction-gas stripping process was coupled with continuous ABE fermentation using immobilized Clostridium acetobutylicum. At the same time, oleyl alcohol was cocurrently flowed into the packed bed reactor with the fresh medium and then recycled back to the packed bed reactor after removing butanol in the stripper. A high glucose consumption of 52 g/L and a high butanol productivity of 11 g/L/h were achieved, resulting in a high butanol yield of 0.21 g-butanol/g-glucose. This can be attributed to both the high bacterial activity for solvent production as well as a threefold increase in the bacterial density inside the packed bed reactor. Also reported is that 64 % of the butanol produced can be recovered by the integrated in situ extraction-gas stripping process. A high butanol productivity and a high glucose consumption were simultaneously achieved. PMID- 27005414 TI - Effects of oxygen and carbon content on nitrogen removal capacities in landfill bioreactors and response of microbial dynamics. AB - In this study, landfill bioreactors were tested to treat the recalcitrant leachate-nitrogen and the impacts of relevant operational parameters on its conversion were comprehensively investigated. We found that the highly diverse microbial community in landfill bioreactors could be substantially affected by increasing biodegradable carbon and oxygen content, which led to the whole system's intrinsic nitrogen removal capacity increasing from 50 to 70 %, and meanwhile, the contribution of anammox was detected less than 20 %. The sequencing and q-PCR results showed that microbial community in bioreactor was dominated by Proteobacteria (~35 %) and Acidobacteria (~20 %) during the whole experiment. The abundance of anammox functioning bacteria (Amx) kept at a stable level (-2.5 to -2.2 log (copies/16S rRNA)) and was not statistically correlated to the abundance of anammox bacteria. However, significant linear correlation (p < 0.05) was determined between the abundance of nirS and Proteobacteria; amoA and AOB. Redundancy analysis (RDA) suggested that although oxygen and biodegradable carbon can both impose effects on microbial community structure, only biodegradable carbon content is the determinant in the total nitrogen removal. PMID- 27005415 TI - Shifts of live bacterial community in secondary effluent by chlorine disinfection revealed by Miseq high-throughput sequencing combined with propidium monoazide treatment. AB - Chlorine disinfection is a commonly used disinfection process in wastewater treatment, but its effects on the indigenous bacterial community in treated wastewater have not been fully elucidated. In this study, secondary effluent samples collected in four wastewater treatment plants (WWTPs) were selected for chlorine disinfection. Shifts in the bacterial community compositions in secondary effluent samples upon chlorine disinfection, both immediately and after 24 h of storage, were investigated using Illumina MiSeq sequencing combined with propidium monoazide (PMA) treatment. The results showed that the phylum Proteobacteria was sensitive to chlorine, with the relative proportions of Proteobacteria decreased from 39.2 to 75.9 % in secondary effluent samples to 7.5 to 62.2 % immediately after chlorine disinfection. The phylogenetic analysis indicated that the most dominant genera belonging to Proteobacteria were sensitive to chlorine. In contrast, the phyla Firmicutes and Planctomycetes showed a certain resistance to chlorine, with their relative proportions increasing from 5.1 to 23.1 % and 0.8 to 9.3 % to 11.3 to 44.6 % and 1.5 to 13.3 %, respectively. Most dominant genera belonging to Firmicutes showed resistance to chlorine. A significant reduction in the richness and diversity of the bacterial community was observed after 24 h of storage of chlorinated secondary effluent. During the 24-h storage process, the relative proportions of most dominant phyla shifted in reverse from the changes induced by chlorine disinfection. Overall, chlorine disinfection not only changes the bacterial community compositions immediately after the disinfection process but also exerts further impacts over a longer period (24 h). PMID- 27005416 TI - Patient treatment in ED hallways and patient perception of clinician-patient communication. PMID- 27005417 TI - One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers. AB - BACKGROUND: The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. RESULTS: Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU's). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilus spp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU's residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). CONCLUSIONS: The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer "starts afresh" and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer. PMID- 27005418 TI - Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity. AB - We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally regulated in the brain. Molecular analysis of patients' variants confirmed expression and translation of truncated transcripts similar to recently characterized alternative terminal exon splice isoforms of KIDINS220 KIDINS220 undergoes extensive alternative splicing in specific neuronal populations and developmental time points, reflecting its complex role in neuronal maturation. In mice and humans, KIDINS220 is alternative spliced in the middle region as well as in the last exon. These full-length and KIDINS220 splice variants occur at precise moments in cortical, hippocampal, and motor neuron development, with splice variants similar to the variants seen in our patients and lacking the last exon of KIDINS220 occurring in adult rather than in embryonic brain. We conducted tissue-specific expression studies in zebrafish that resulted in spasms, confirming a functional link with disruption of the KIDINS220 levels in developing neurites. This work reveals a crucial physiological role of KIDINS220 in development and provides insight into how perturbation of the complex interplay of KIDINS220 isoforms and their relative expression can affect neuron control and human metabolism. Altogether, we here show that de novo protein truncating KIDINS220 variants cause a new syndrome, SINO. This is the first report of KIDINS220 variants causing a human disease. PMID- 27005419 TI - Genome wide association study identifies two loci associated with cadmium in erythrocytes among never-smokers. AB - BACKGROUND: Cadmium is a non-essential toxic metal with multiple adverse health effects. Exposure in the general population occurs by smoking and diet. Cadmium in erythrocytes is a valid biomarker of exposure and body burden of cadmium. OBJECTIVES: We aimed to identify genetic variants related to concentrations of cadmium in erythrocytes. METHODS: Erythrocyte cadmium was analyzed in 4432 individuals (1728 never smokers) from the Swedish population-based Malmo Diet and Cancer cohort. Genotyping was performed using the Illumina HumanOmniExpressExome Bead chip with genome-wide coverage. Genome wide analyses were performed in the whole sample and in never smokers. RESULTS: No single nucleotide polymorphism (SNP) reached a genome-wide significant association with erythrocyte cadmium in the whole sample. However, in never smokers, 14 variants showed genome-wide significant relationships with erythrocyte cadmium after adjusting for age and sex. Thirteen variants were in linkage disequilibrium on chromosome 8q13.3 in the XKR9 and LACTB2 genes. The lead SNP on 8q13.3 was rs12681420 (minor allele G, minor allele frequency [MAF] = 0.46, beta: -0.11, P = 3.48 * 10-11), an intron variant within the XKR9 gene. The other significant locus, rs17574271 (minor allele C, MAF = 0.09, beta: 0.17, P = 6.18 * 10-9), was an intron variant within the DLGAP1 gene at chromosome 18p11.31. CONCLUSION: This genome-wide study of never smokers from the general population identified two independent regions related to erythrocyte cadmium. The strongest locus covers the XKR9 and LACTB2 genes, which both could have related functions in cadmium absorption and metabolism. Replication studies are needed to confirm the findings and mechanisms should be further investigated. PMID- 27005420 TI - Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy). AB - Limb girdle muscular dystrophy 2A is due to loss-of-function mutations in the Calpain 3 (CAPN3) gene. Our previous data suggest that CAPN3 helps to maintain the integrity of the triad complex in skeletal muscle. In Capn3 knock-out mice (C3KO), Ca2+ release and Ca2+/calmodulin kinase II (CaMKII) signaling are attenuated. We hypothesized that calpainopathy may result from a failure to transmit loading-induced Ca2+-mediated signals, necessary to up-regulate expression of muscle adaptation genes. To test this hypothesis, we compared transcriptomes of muscles from wild type (WT) and C3KO mice subjected to endurance exercise. In WT mice, exercise induces a gene signature that includes myofibrillar, mitochondrial and oxidative lipid metabolism genes, necessary for muscle adaptation. C3KO muscles fail to activate the same gene signature. Furthermore, in agreement with the aberrant transcriptional profile, we observe a commensurate functional defect in lipid metabolism whereby C3KO muscles fail to release fatty acids from stored triacylglycerol. In conjunction with the defects in oxidative metabolism, C3KO mice demonstrate reduced exercise endurance. Failure to up-regulate genes in C3KO muscles is due, in part, to decreased levels of PGC1alpha, a transcriptional co-regulator that orchestrates the muscle adaptation response. Destabilization of PGC1alpha is attributable to decreased p38 MAPK activation via diminished CaMKII signaling. Thus, we elucidate a pathway downstream of Ca2+-mediated CaMKII activation that is dysfunctional in C3KO mice, leading to reduced transcription of genes involved in muscle adaptation. These studies identify a novel mechanism of muscular dystrophy: a blunted transcriptional response to muscle loading resulting in chronic failure to adapt and remodel. PMID- 27005422 TI - Cell-type-specific miR-431 dysregulation in a motor neuron model of spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is an autosomal-recessive pediatric neurodegenerative disease characterized by selective loss of spinal motor neurons. It is caused by mutation in the survival of motor neuron 1, SMN1, gene and leads to loss of function of the full-length SMN protein. microRNAs (miRNAs) are small RNAs that are involved in post-transcriptional regulation of gene expression. Prior studies have implicated miRNAs in the pathogenesis of motor neuron disease. We hypothesized that motor neuron-specific miRNA expression changes are involved in their selective vulnerability in SMA. Therefore, we sought to determine the effect of SMN loss on miRNAs and their target mRNAs in spinal motor neurons. We used microarray and RNAseq to profile both miRNA and mRNA expression in primary spinal motor neuron cultures after acute SMN knockdown. By integrating the miRNA:mRNA profiles, a number of dysregulated miRNAs were identified with enrichment in differentially expressed putative mRNA targets. miR-431 expression was highly increased, and a number of its putative mRNA targets were significantly downregulated in motor neurons after SMN loss. Further, we found that miR-431 regulates motor neuron neurite length by targeting several molecules previously identified to play a role in motor neuron axon outgrowth, including chondrolectin. Together, our findings indicate that cell type-specific dysregulation of miR-431 plays a role in the SMA motor neuron phenotype. PMID- 27005421 TI - 5-Hydroxymethylcytosine-mediated alteration of transposon activity associated with the exposure to adverse in utero environments in human. AB - Preeclampsia and gestational diabetes mellitus (GDM) are the most common clinical conditions in pregnancy that could result in adverse in utero environments. Fetal exposure to poor environments may raise the long-term risk of postnatal disorders, while epigenetic modifications could be involved. Recent research has implicated involvement of 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine, via oxidation by ten-eleven translocation (TET) enzymes, in DNA methylation-related plasticity. Here, we show that the TET2 expression and 5hmC abundance are significantly altered in the umbilical veins of GDM and preeclampsia. Genome-wide profiling of 5hmC revealed its specific reduction on intragenic regions from both GDM and preeclampsia compared to healthy controls. Gene Ontology analysis using loci bearing unique GDM- and preeclampsia-specific loss-of-5hmC indicated its impact on several critical biological pathways. Interestingly, the substantial alteration of 5hmC on several transposons and repetitive elements led to their differential expression. The alteration of TET expression, 5hmC levels and 5hmC-mediated transposon activity was further confirmed using established hypoxia cell culture model, which could be rescued by vitamin C, a known activator of TET proteins. Together, these results suggest that adverse pregnancy environments could influence 5hmC-mediated epigenetic profile and contribute to abnormal development of fetal vascular systems that may lead to postnatal diseases. PMID- 27005423 TI - Molecular basis of classic galactosemia from the structure of human galactose 1 phosphate uridylyltransferase. AB - Classic galactosemia is a potentially lethal disease caused by the dysfunction of galactose 1-phosphate uridylyltransferase (GALT). Over 300 disease-associated GALT mutations have been reported, with the majority being missense changes, although a better understanding of their underlying molecular effects has been hindered by the lack of structural information for the human enzyme. Here, we present the 1.9 A resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer. hGALT reveals significant structural differences from bacterial GALT homologues in metal ligation and dimer interactions, and therefore is a zbetter model for understanding the molecular consequences of disease mutations. Both uridylylation and zinc binding influence the stability and aggregation tendency of hGALT. This has implications for disease-associated variants where p.Gln188Arg, the most commonly detected, increases the rate of aggregation in the absence of zinc likely due to its reduced ability to form the uridylylated intermediate. As such our structure serves as a template in the future design of pharmacological chaperone therapies and opens new concepts about the roles of metal binding and activity in protein misfolding by disease associated mutants. PMID- 27005425 TI - Mental health for all Australians. PMID- 27005426 TI - Why the hype about subtype? Bipolar I, bipolar II--it's simply bipolar, through and through! PMID- 27005424 TI - Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease. AB - To identify new risk loci for colorectal cancer (CRC), we conducted a meta analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 * 10-8, odds ratio = 1.10, 95% confidence interval = 1.06 1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r2 = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD. PMID- 27005427 TI - Best strategies for reducing the suicide rate in Australia: response to Pirkis. PMID- 27005428 TI - Facile preparation of multifunctional superparamagnetic PHBV microspheres containing SPIONs for biomedical applications. AB - The promising potential of magnetic polymer microspheres in various biomedical applications has been frequently reported. However, the surface hydrophilicity of superparamagnetic iron oxide nanoparticles (SPIONs) usually leads to poor or even failed encapsulation of SPIONs in hydrophobic polymer microspheres using the emulsion method. In this study, the stability of SPIONs in poly(3-hydroxybutyrate co-3-hydroxyvalerate) (PHBV) solution was significantly increased after surface modification with lauric acid. As a result, magnetic PHBV microspheres with high encapsulation efficiencies (71.0-87.4%) were prepared using emulsion-solvent extraction/evaporation method. Magnetic resonance imaging (MRI) showed significant contrast for the magnetic PHBV microspheres. The toxicity of these magnetic PHBV microspheres towards human T-lymphoma suspension cells and adherent colon carcinoma HT-29 cells was investigated using flow cytometry, and they were shown to be non-toxic in a broad concentration range. A model drug, tetracycline hydrochloride, was used to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres. The drug was successfully loaded into the microspheres using lauric acid-coated SPIONs as drug carrier, and was released from the microspheres in a diffusion controlled manner. The developed magnetic PHBV microspheres are promising candidates for biomedical applications such as targeted drug delivery and MRI. PMID- 27005429 TI - Preservation of methylated CpG dinucleotides in human CpG islands. AB - BACKGROUND: CpG dinucleotides are extensively underrepresented in mammalian genomes. It is widely accepted that genome-wide CpG depletion is predominantly caused by an elevated CpG > TpG mutation rate due to frequent cytosine methylation in the CpG context. Meanwhile the CpG content in genomic regions called CpG islands (CGIs) is noticeably higher. This observation is usually explained by lower CpG > TpG substitution rates within CGIs due to reduced cytosine methylation levels. RESULTS: By combining genome-wide data on substitutions and methylation levels in several human cell types we have shown that cytosine methylation in human sperm cells was strongly and consistently associated with increased CpG > TpG substitution rates. In contrast, this correlation was not observed for embryonic stem cells or fibroblasts. Surprisingly, the decreased sperm CpG methylation level was insufficient to explain the reduced CpG > TpG substitution rates in CGIs. CONCLUSIONS: While cytosine methylation in human sperm cells is strongly associated with increased CpG > TpG substitution rates, substitution rates are significantly reduced within CGIs even after sperm CpG methylation levels and local GC content are controlled for. Our findings are consistent with strong negative selection preserving methylated CpGs within CGIs including intergenic ones. PMID- 27005430 TI - Biological control of Ixodes ricinus larvae and nymphs with Metarhizium anisopliae blastospores. AB - The entomopathogenic fungus Metarhizium anisopliae is used as a biological pest control agent against various arthropod species, including ticks. However, the efficacy depends on tick species, tick stage and fungus strain. We studied the effect of M. anisopliae on engorged larvae and nymphs of Ixodes ricinus, the most abundant tick species in Europe, under laboratory and semi-field conditions. A significant reduction of engorged larvae and nymphs could be shown under laboratory as well as under semi-field conditions. Only 3.5% of the larvae treated in the lab and only 18.5% kept under semi-field conditions were able to develop into nymphs compared to the recovered nymphs of the control groups, which were regarded as 100%. Only 7.1% of nymphs were recovered as adult ticks after fungal treatment under semi-field conditions compared to the control (100%). The efficacy of blastospores of M. anisopliae against engorged larvae and nymphs of I. ricinus under semi-field conditions was demonstrated in this study, showing their high potential as a biological control agent of ticks. Further studies will have to investigate the effect of this agent against other stages of I. ricinus as well as other tick species before its value as a biological control agent against ticks can be fully assessed. PMID- 27005431 TI - Intra-fraction motion of the prostate is not increased by patient couch shifts. AB - BACKGROUND: During a fraction of external beam radiotherapy for prostate cancer, a mismatch between target volume and dose coverage may accumulate over time due to intra-fraction motion. One way to remove the residual error is to perform a couch shift in opposite direction. In principle, such couch shifts could cause secondary displacements of the patient and prostate. Hence it is interesting to investigate if couch shifts might amplify intra-fraction motion. FINDINGS: Intra fraction motion of the prostate and patient couch position were simultaneously recorded during 359 fractions in 15 patients. During this time, a total of 22 couch shifts of up to 31.5 mm along different axes were recorded. Prostate position and couch position were plotted before, during and after each couch shift. There was no visible impact of couch shifts on prostate motion. The standard deviation of prostate position was calculated before, during and after each couch shift. The standard deviation did not significantly increase during couch shifts (by 3 % on average, p = 0.88) and even slightly decreased after a couch shift (by 37 % on average; p = 0.02). CONCLUSIONS: Shifts of the patient couch did not adversely affect the motion of the prostate relative to the patient couch. Hence, shifts of the patient couch may be a viable way to correct the position of the prostate relative to the dose distribution. PMID- 27005432 TI - Functional and structural characterization of two Bacillus megaterium nitroreductases biotransforming the herbicide mesotrione. AB - Mesotrione is a selective herbicide belonging to the triketone family, commonly used on maize cultures since 2003. A mesotrione-transforming Bacillus megaterium Mes11 strain isolated from an agricultural soil was used as a model to identify the key enzymes initiating the biotransformation of this herbicide. Two enzymes (called NfrA1 and NfrA2/YcnD) were identified, and functionally and structurally characterized. Both belong to the NfsA FRP family of the nitro-FMN reductase superfamily (type I oxygen-insensitive nitroreductase) and show optimal pH and temperature of 6-6.5 and 23-25 degrees C, respectively. Both undergo a Ping Pong Bi Bi mechanism, with NADPH and NADPH/NADH as cofactors for NfrA1 and NfrA2/YcnD, respectively. It is interesting that both can also reduce various nitro compounds including pesticides, antibiotics, one prodrug and 4-methylsulfonyl-2 nitrobenzoic acid, one of the mesotrione metabolites retrieved from the environment. The present study constitutes the first identification of mesotrione transforming enzymes. These enzymes (or their corresponding genes) could be used as biomarkers to predict the capacity of ecosystems to transform mesotrione and assess their contamination by both the parent molecule and/or the metabolites. PMID- 27005433 TI - Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review. AB - BACKGROUND: Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods. METHODS: We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses. RESULTS: Twenty five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data. CONCLUSIONS: As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission. PMID- 27005434 TI - Growing media constituents determine the microbial nitrogen conversions in organic growing media for horticulture. AB - Vegetables and fruits are an important part of a healthy food diet, however, the eco-sustainability of the production of these can still be significantly improved. European farmers and consumers spend an estimated ?15.5 billion per year on inorganic fertilizers and the production of N-fertilizers results in a high carbon footprint. We investigated if fertilizer type and medium constituents determine microbial nitrogen conversions in organic growing media and can be used as a next step towards a more sustainable horticulture. We demonstrated that growing media constituents showed differences in urea hydrolysis, ammonia and nitrite oxidation and in carbon dioxide respiration rate. Interestingly, mixing of the growing media constituents resulted in a stimulation of the function of the microorganisms. The use of organic fertilizer resulted in an increase in amoA gene copy number by factor 100 compared to inorganic fertilizers. Our results support our hypothesis that the activity of the functional microbial community with respect to nitrogen turnover in an organic growing medium can be improved by selecting and mixing the appropriate growing media components with each other. These findings contribute to the understanding of the functional microbial community in growing media and its potential role towards a more responsible horticulture. PMID- 27005435 TI - Individual heritable differences result in unique cell lymphocyte receptor repertoires of naive and antigen-experienced cells. AB - The adaptive immune system's capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire. However, the influence of individual genetic and epigenetic differences on these repertoires is not typically measured. By leveraging the unique characteristics of B, CD4(+) T and CD8(+) T-lymphocyte subsets from monozygotic twins, we quantify the impact of heritable factors on both the V(D)J recombination process and on thymic selection. We show that the resulting biases in both V(D)J usage and N/P addition lengths, which are found in naive and antigen experienced cells, contribute to significant variation in the CDR3 region. Moreover, we show that the relative usage of V and J gene segments is chromosomally biased, with ~1.5 times as many rearrangements originating from a single chromosome. These data refine our understanding of the heritable mechanisms affecting the repertoire, and show that biases are evident on a chromosome-wide level. PMID- 27005436 TI - Gene-based aggregate SNP associations between candidate AD genes and cognitive decline. AB - Single nucleotide polymorphisms (SNPs) in and near ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, complement receptor 1 (CR1), EPHA1, EXOC3L2, FERMT2, HLA cluster (DRB5-DQA), INPP5D, MEF2C, MS4A cluster (MS4A3-MS4A6E), NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1 have been associated with Alzheimer's disease (AD) in large meta-analyses. We aimed to determine whether established AD associated genes are associated with longitudinal cognitive decline by examining aggregate variation across these gene regions. In two single-sex cohorts of older, community-dwelling adults, we examined the association between SNPs in previously implicated gene regions and cognitive decline (age-adjusted person specific cognitive slopes) using a Sequence Kernel Association Test (SKAT). In regions which showed aggregate significance, we examined the univariate association between individual SNPs in the region and cognitive decline. Only two of the original AD-associated SNPs were significantly associated with cognitive decline in our cohorts. We identified significant aggregate-level associations between cognitive decline and the gene regions BIN1, CD33, CELF1, CR1, HLA cluster, and MEF2C in the all-female cohort and significant associations with ABCA7, HLA cluster, MS4A6E, PICALM, PTK2B, SLC24A4, and SORL1 in the all-male cohort. We also identified a block of eight correlated SNPs in CD33 and several blocks of correlated SNPs in CELF1 that were significantly associated with cognitive decline in univariate analysis in the all-female cohort. PMID- 27005437 TI - Addiction: A preclinical and clinical analysis. PMID- 27005438 TI - The 5-Lipoxygenase as modulator of Alzheimer's gamma-secretase and therapeutic target. AB - Alzheimer's disease (AD) is an age-related, neurodegenerative disorder characterized by cognitive impairment with memory loss, extracellular amyloid beta (Abeta) peptides aggregation, and intracellular hyper-phosphorylated tau neurofibrillary tangles (NFT) accumulation. Although the 5-lipoxygenase (5LO) protein enzyme is well known as an important modulators of oxidation and inflammation, recent work has highlighted the new hypothesis that this pathway may play a direct role in AD pathogenesis. In this review article, we will discuss how the 5LO via the gamma-secretase influences Abeta peptides formation, and other molecular pathologies including neuroinflammation, synaptic integrity, and cognitive functions, and provide an assessment of how targeting this protein could lead to novel therapeutics for AD and other related neurodegenerative disorders. PMID- 27005439 TI - Botulinum Toxin Dosing Trends in Spasmodic Dysphonia Over a 20-year Period. AB - OBJECTIVES: The study aims to (1) identify the botulinum toxin (BTX) dosing trend in a cohort of patients who received at least 20 injections for the treatment of adductor spasmodic dysphonia (ADSD), (2) describe two distinct BTX dosing trends in treating ADSD (a "classic" dosing trend that initially decreases before stabilizing, and a "fluctuating" dosing trend), and (3) determine if patients with the "classic" dosing trend differed in age or in dosing intervals from those with the "fluctuating" dosing trend. STUDY DESIGN: This is a retrospective case series. METHODS: Of 149 patients who received a total of 2484 BTX injections for the treatment of spasmodic dysphonia in 1993-2013, 49 patients received at least 20 injections. The BTX dose and the interval between doses were recorded. The mean dose of injections 1-20 was determined. The age at initial injection, initial dose, and interval in days between treatments were compared for the "fluctuating" and "classic" groups. RESULTS: The cohort exhibits a significant decrease in dose during the first 10-15 injections. The "fluctuating" group had a significantly shorter interval between injections (mean interval = 97.09 days, SD = 29.41; mean interval = 136.90 days, SD = 43.76, P = 0.002). The mean age at initial dose was not significantly different between the "classic" and "fluctuating" groups. CONCLUSIONS: The average BTX dose of patients with ADSD who receive long-term injections significantly decreases during the initial 10-15 injections before stabilizing. Patients who exhibit the "fluctuating" dosing pattern have a significantly shorter interval between injections than those with the "classic" dosing pattern. PMID- 27005440 TI - The Instrument of Voice: The "True" Vocal Cord or Vocal Fold? PMID- 27005441 TI - Chemoradiation versus chemotherapy or radiation alone in stage III endometrial cancer: Patterns of care and impact on overall survival. AB - PURPOSE: We aimed to investigate the patterns-of-care and overall survival (OS) benefit of aCRT versus adjuvant monotherapy (aMT), defined as either chemotherapy or radiation alone, utilizing a large national registry of patients. PATIENTS AND METHODS: Adult patients with stage III endometrial adenocarcinoma diagnosed from 2004 to 2013 were included. Logistic and Cox regression modeling was used to identify factors predictive of receipt of aCRT and OS, respectively. Survival analysis was performed with Kaplan Meier and log-rank analysis. Propensity score matching and sensitivity analysis was performed to address selection bias and presence of potential confounding variables. RESULTS: A total of 21,027 patients were identified: 11,435 (54.4%) patients received aMT, while 9592 (45.6%) received aCRT. Utilization of aCRT increased over the study period (p<0.01). Factors predictive of receiving aCRT include private insurance (OR: 1.67, 95% CI: 1.30-2.14), Medicare (OR: 1.33, 95% CI: 1.01-1.75), FIGO stage IIIC disease (OR: 1.36, 95% CI: 1.19-1.54), lymphovascular space invasion (OR: 1.14, 95% CI: 1.03 1.27), and lymph node surgery performed (OR: 1.42, 95% CI: 1.15-1.74). Median survival in years for aCRT, RT, and CT was 10.3, 7.1, and 5.6, respectively (p<0.001). Compared to aMT, aCRT was associated with a decrease risk of death on multivariate analysis (HR: 0.62, 95% CI: 0.56-0.70). The benefit of aCRT over aMT persisted after propensity score matching. CONCLUSION: The use of aCRT for stage III endometrial cancer is increasing. Multiple clinical and demographic factors were predictive of aCRT use. When compared to chemotherapy or radiation alone, aCRT is associated with an OS benefit. PMID- 27005442 TI - CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204. AB - T lymphocytes stimulated through their antigen receptor (TCR) preferentially express mRNA isoforms with shorter 3' untranslated regions (3'-UTRs) derived from alternative pre-mRNA cleavage and polyadenylation (APA). However, the physiological relevance of APA programs remains poorly understood. CD5 is a T cell surface glycoprotein that negatively regulates TCR signaling from the onset of T-cell activation. CD5 plays a pivotal role in mediating outcomes of cell survival or apoptosis, and may prevent both autoimmunity and cancer. In human primary T lymphocytes and Jurkat cells we found three distinct mRNA isoforms encoding CD5, each derived from distinct poly(A) signals (PASs). Upon T-cell activation, there is an overall increase in CD5 mRNAs with a specific increase in the relative expression of the shorter isoforms. 3'-UTRs derived from these shorter isoforms confer higher reporter expression in activated T cells relative to the longer isoform. We further show that polypyrimidine tract binding protein (PTB/PTBP1) directly binds to the proximal PAS and PTB siRNA depletion causes a decrease in mRNA derived from this PAS, suggesting an effect on stability or poly(A) site selection to circumvent targeting of the longer CD5 mRNA isoform by miR-204. These mechanisms fine-tune CD5 expression levels and thus ultimately T cell responses. PMID- 27005443 TI - Validation of obesity susceptibility loci identified by genome-wide association studies in early childhood in South Brazilian children. AB - BACKGROUND: The prevalence of childhood obesity has been dramatically increasing in developing countries as it has been reported for developed nations. Identifying susceptibility genes in early life could provide the foundations for interventions in lifestyle to prevent obese children to become obese adults. OBJECTIVES: The objective of this study was to evaluate the influence of genetic variants related to obesity identified by genome-wide association studies (MC4R, TMEM18, KCTD15, SH2B1, SEC16B, BDNF, NEGR1, OLFM4 and HOXB5 genes) on anthropometric and dietary phenotypes in two Brazilian cohorts followed-up since birth. METHODS: There were 745 children examined at birth, after 1 year and after 3.5 years of follow-up. Ten single nucleotide polymorphisms were genotyped. Anthropometric and dietary parameters were compared among genotypes. Children were classified as overweight when body mass index Z-score was >+1. RESULTS: Overweight prevalence was 30.7% at 3.5 years old. Significant associations were identified at 3.5 years old for TMEM18 rs6548238, NEGR1 rs2815752, BDNF rs10767664 and rs6265 (1 year old and 3.5 years old) with anthropometric phenotypes and at 3.5 years old for SEC16B rs10913469 with dietary parameters. CONCLUSIONS: Our results indicate that genetic variants in/near these genes contribute to obesity susceptibility in childhood and highlight the age at which they begin to affect obesity-related phenotypes. PMID- 27005445 TI - Temporal Dynamics of Collaborative Networks in Large Scientific Consortia. AB - The emergence of collective creative enterprise such as large scientific consortia is a unique feature in modern scientific research. We analyzed the temporal co-authorship network structures of ENCODE and modENCODE consortia. Our analysis revealed that the consortium members work closely as a community whereas non-members collaborate in the scale of a few laboratories. We also identified a few brokers playing an important role to facilitate collaborations with outside researchers. PMID- 27005446 TI - Comment on the letter to the editor concerning manuscript: "Therapeutic hypothermia for adult community-acquired bacterial meningitis-historical control study". PMID- 27005444 TI - New Insights into the Regulation of Heterochromatin. AB - All living organisms are constantly exposed to stresses from internal biological processes and surrounding environments, which induce many adaptive changes in cellular physiology and gene expression programs. Unexpectedly, constitutive heterochromatin, which is generally associated with the stable maintenance of gene silencing, is also dynamically regulated in response to stimuli. In this review we discuss the mechanism of constitutive heterochromatin assembly, its dynamic nature, and its responses to environmental changes. PMID- 27005447 TI - Unraveling the Effects of PPARbeta/delta on Insulin Resistance and Cardiovascular Disease. AB - Insulin resistance precedes dyslipidemia and type 2 diabetes mellitus (T2DM) development. Preclinical evidence suggests that peroxisome proliferator-activated receptor (PPAR) beta/delta activators may prevent and treat obesity-induced insulin resistance and T2DM, while clinical trials highlight their potential utility in dyslipidemia. This review summarizes recent mechanistic insights into the antidiabetic effects of PPARbeta/delta activators, including their anti inflammatory actions, their ability to inhibit endoplasmic reticulum (ER) stress and hepatic lipogenesis, and to improve atherogenesis and insulin sensitivity, as well as their capacity to activate pathways that are also stimulated by exercise. Findings from clinical trials are also examined. Dissecting the effects of PPARbeta/delta ligands on insulin sensitivity and atherogenesis may provide a basis for the development of therapies for the prevention and treatment of T2DM and cardiovascular disease (CVD). PMID- 27005448 TI - Identifying Elder Abuse in the Emergency Department: Toward a Multidisciplinary Team-Based Approach. PMID- 27005449 TI - The Forensic Lens: Bringing Elder Neglect Into Focus in the Emergency Department. AB - We present 2 case studies of older patients who were brought to the emergency department (ED) in severely debilitated states. Both presented with severe malnutrition, contractures, and decubitus ulcers, and were nonverbal, with histories of dementia and end-stage disease. Their primary caregivers, adult children, were uncooperative with Adult Protective Services and disregarded treatment recommendations. Although both elders had signs suspicious for neglect, a comprehensive review revealed many layers of complexity. We use these cases to illustrate an approach to the assessment of possible elder neglect in ED settings and how to intervene to ensure patient safety. We begin with a discussion of the differences between willful, unintentional, and unsubstantiated neglect by a caregiver and then describe when to suspect neglect by evaluating the elder, interviewing the caregiver and first responders, assessing the caregiver's ability to meet the elder's needs, and, if possible, obtaining medical history and information about the home care environment. These cases illustrate the importance of careful documentation in cases of suspected neglect to assist investigative agencies, reduce the risk of further harm, and improve patient outcomes. PMID- 27005450 TI - Autonomous immunity in mucosal epithelial cells: fortifying the barrier against infection. AB - Mucosal epithelial cells express an autonomous innate immune response that controls the overgrowth of invaded bacteria, mitigates the harmful effects of the bacteria carried within, and does not rely on other external arms of the immune response. Epithelial cell autonomous innate immunity "respects" the social biology of invading bacteria to achieve symbiosis, and is the primary protective mechanism against pathogens. PMID- 27005451 TI - Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation. AB - The heterodimeric mycobacterial receptors, macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle), are upregulated at the cell surface following microbial challenge, but the mechanisms underlying this response are unclear. Here we report that microbial stimulation triggers Mincle expression through the myeloid differentiation primary response gene 88 (MyD88) pathway; a process that does not require MCL. Conversely, we show that MCL is constitutively expressed but retained intracellularly until Mincle is induced, whereupon the receptors form heterodimers which are translocated to the cell surface. Thus this "two-step" model for induction of these key receptors provides new insights into the underlying mechanisms of anti-mycobacterial immunity. PMID- 27005452 TI - An outbreak of scrub typhus in military personnel despite protocols for antibiotic prophylaxis: doxycycline resistance excluded by a quantitative PCR based susceptibility assay. AB - Scrub typhus is caused by the obligate intracellular bacterium Orientia tsutsugamushi and is endemic to many countries in the Asia-Pacific region, including tropical Australia. We describe a recent large outbreak amongst military personnel in north Queensland. A total of 45 clinical cases were identified (36% of all potentially exposed individuals). This occurred despite existing military protocols stipulating the provision of doxycycline prophylaxis. Doxycycline resistance in O. tsutsugamushi has been described in South-East Asia, but not Australia. In one case, O. tsutsugamushi was cultured from eschar tissue and blood. Using quantitative real-time PCR to determine susceptibility to doxycycline for the outbreak strain, a minimum inhibitory concentration (MIC) of <=0.04 MUg/mL was found, indicating susceptibility to this agent. It seems most probable that failure to adhere to adequate prophylaxis over the duration of the military exercise accounted for the large number of cases encountered rather than doxycycline resistance. PMID- 27005453 TI - Toward DNA electrochemical sensing by free-standing ZnO nanosheets grown on 2D thin-layered MoS2. AB - Very recently, the 2-dimensional MoS2 layer as base substrate integrated with other materials has caused people's emerging attention. In this paper, a thin layered MoS2 was prepared through an ultrasonic exfoliation method from bulk MoS2 and then the free-standing ZnO nanosheet was electrodeposited on the MoS2 scaffold for DNA sensing. The ZnO/MoS2 nanocomposite revealed smooth and vertical nanosheets morphology by scanning electron microscopy, compared with the sole MoS2 and sole ZnO. Importantly, the partially negative charged MoS2 layer is beneficial to the nucleation and growth of ZnO nanosheets under the effect of electrostatic interactions. Classic methylene blue, which possesses different affinities to dsDNA and ssDNA, was adopted as the measure signal to confirm the immobilization and hybridization of DNA on ZnO nanosheets and pursue the optimal synthetic conditions. And the results demonstrated that the free-standing ZnO/MoS2 nanosheets had low detection limit (6.6*10-16M) and has a positive influence on DNA immobilization and hybridization. PMID- 27005454 TI - The application of graphene for in vitro and in vivo electrochemical biosensing. AB - Advances in analysis are required for rapid and reliable clinical diagnosis. Graphene is a 2D material that has been extensively used in the development of devices for the medical proposes due to properties such as an elevated surface area and excellent electrical conductivity. On the other hand, architectures have been designed with the incorporation of different biological recognition elements such as antibodies/antigens and DNA probes for the proposition of immunosensors and genosensors. This field presents a great progress in the last few years, which have opened up a wide range of applications. Here, we highlight a rather comprehensive overview of the interesting properties of graphene for in vitro, in vivo, and point-of-care electrochemical biosensing. In the course of the paper, we first introduce graphene, electroanalytical methods (potentiometry, voltammetry, amperometry and electrochemical impedance spectroscopy) followed by an overview of the prospects and possible applications of this material in electrochemical biosensors. In this context, we discuss some relevant trends including the monitoring of multiple biomarkers for cancer diagnostic, implantable devices for in vivo sensing and, development of point-of-care devices to real-time diagnostics. PMID- 27005455 TI - Comparison of O2 and EtCO2 achieved by the polypropylene and conventional polyvinyl chloride face mask in healthy individuals. PMID- 27005456 TI - Vestibular evoked myogenic potentials (VEMPs): Tailoring methodology to specific conditions. PMID- 27005457 TI - New drugs for the treatment of complicated intra-abdominal infections in the era of increasing antimicrobial resistance. AB - The continuing increase in multidrug-resistant organisms (MDROs) worldwide has created new challenges in treating complicated intra-abdominal infections (cIAIs). A number of novel antimicrobial agents have been developed against resistant pathogens. To target extended-spectrum beta-lactamase (ESBL)-producing pathogens, novel beta-lactam antibiotics, such as ceftolozane/tazobactam, ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and S-649266, are antimicrobial alternatives for cIAIs. Two new drugs, eravacycline and plazomicin, have activity against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, carbapenem-resistant Acinetobacter baumannii and ESBL-producers. New lipoglycopeptides and oxazolidinones provide feasible options against resistant Gram-positive pathogens. These novel antimicrobials may play a role in improving the clinical outcomes of cIAIs caused by MDROs. PMID- 27005458 TI - Empirical third-generation cephalosporin therapy for adults with community-onset Enterobacteriaceae bacteraemia: Impact of revised CLSI breakpoints. AB - Third-generation cephalosporins (3GCs) [ceftriaxone (CRO) and cefotaxime (CTX)] have remarkable potency against Enterobacteriaceae and are commonly prescribed for the treatment of community-onset bacteraemia. However, clinical evidence supporting the updated interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI) is limited. Adults with community-onset monomicrobial Enterobacteriaceae bacteraemia treated empirically with CRO or CTX were recruited. Clinical information was collected from medical records and CTX MICs were determined using the broth microdilution method. Eligible patients (n=409) were categorised into de-escalation (260; 63.6%), no switch (115; 28.1%) and escalation (34; 8.3%) groups according to the type of definitive antibiotics. Multivariate regression revealed five independent predictors of 28-day mortality: fatal co-morbidities based on McCabe classification [odds ratio (OR)=19.96; P<0.001]; high Pitt bacteraemia score (>=4) at bacteraemia onset (OR=13.91; P<0.001); bacteraemia because of pneumonia (OR=5.45; P=0.007); de-escalation after empirical therapy (OR=0.28; P=0.03); and isolates with a CTX MIC<=1mg/L (OR=0.17; P=0.02). Of note, isolates with a CTX MIC<=8mg/L (indicated as susceptible by previous CLSI breakpoints) were not associated with mortality. Furthermore, clinical failure and 28-day mortality rates had a tendency to increase with increasing CTX MIC (gamma=1.00; P=0.01). Conclusively, focusing on patients with community-onset Enterobacteriaceae bacteraemia receiving empirical 3GC therapy, the present study provides clinically critical evidence to validate the proposed reduction in the susceptibility breakpoint of CTX to MIC<=1mg/L. PMID- 27005459 TI - Epidemiology and antimicrobial susceptibility profiles of pathogens causing urinary tract infections in the Asia-Pacific region: Results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2010-2013. AB - A total of 9599 isolates of Gram-negative bacteria (GNB) causing urinary tract infections (UTIs) were collected from 60 centres in 13 countries in the Asia Pacific region from 2010-2013. These isolates comprised Enterobacteriaceae species (mainly Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Enterobacter cloacae and Morganella morganii) and non fermentative GNB species (predominantly Pseudomonas aeruginosa and Acinetobacter baumannii). In vitro susceptibilities were determined by the agar dilution method and susceptibility profiles were determined using the minimum inhibitory concentration (MIC) interpretive breakpoints recommended by the Clinical and Laboratory Standards Institute in 2015. Production of extended-spectrum beta lactamases (ESBLs) amongst E. coli, K. pneumoniae, P. mirabilis and K. oxytoca isolates was determined by the double-disk synergy test. China, Vietnam, India, Thailand and the Philippines had the highest rates of GNB species producing ESBLs and the highest rates of cephalosporin resistance. ESBL production and hospital acquired infection (isolates obtained >=48 h after admission) significantly compromised the susceptibility of isolates of E. coli and K. pneumoniae to ciprofloxacin, levofloxacin and most beta-lactams, with the exception of imipenem and ertapenem. However, >87% of ESBL-producing E. coli strains were susceptible to amikacin and piperacillin/tazobactam, indicating that these antibiotics might be appropriate alternatives for treating UTIs due to ESBL-producing E. coli. Fluoroquinolones were shown to be inappropriate as empirical therapy for UTIs. Antibiotic resistance is a serious problem in the Asia-Pacific region. Therefore, continuous monitoring of evolutionary trends in the susceptibility profiles of GNB causing UTIs in Asia is crucial. PMID- 27005460 TI - Carbapenemase-producing Klebsiella pneumoniae bloodstream infections in neutropenic patients with haematological malignancies or aplastic anaemia: Analysis of 50 cases. AB - Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) are currently among the most important nosocomial pathogens in many geographic regions. A retrospective study was conducted between 2010 and 2014 in four hospitals located in a high prevalence area (Athens, Greece) to describe the clinical features, treatment and outcomes of neutropenic patients with haematological diseases complicated with CP Kp bloodstream infections. A total of 50 patients were identified, including 48 with haematological malignancies and 2 with aplastic anaemia. All patients had neutropenia (<500 cells/mm(3)), of whom 40 had <100 neutrophils/mm(3). The probable source of bacteraemia was identified in 9 patients; in the remaining 41 patients the bacteraemia was considered primary. For definitive treatment, 30 patients received combination therapy (two or more active drugs), 10 received monotherapy (one active drug) and 4 received therapy with no active drug; the remaining 6 patients died within 48 h after the onset of bacteraemia. The 14-day all-cause mortality rate was 50%, 38% and 33% for those who received one, two or three active drugs respectively. In the Cox proportional hazards model, unresolved neutropenia [hazard ratio (HR)=19.28, 95% confidence interval (CI) 2.31-160.69; P=0.006], septic shock (HR=3.04, 95% CI 1.06-8.78; P=0.04) and treatment with one active drug (HR for monotherapy versus combination therapy=3.95, 95% CI 1.23-12.65; P=0.02) were independent predictors of death, whilst combination therapy was associated with lower mortality. These findings may assist physicians in making treatment decisions for neutropenic patients with CP-Kp infections. PMID- 27005461 TI - Correlates of prescription opioid therapy in Veterans with chronic pain and history of substance use disorder. AB - Patients with a history of substance use disorder (SUD) are more likely to be prescribed opioid medications for chronic pain than patients without an SUD history; however, little is known about prescription opioid therapy in populations composed exclusively of patients with SUD. This study examined correlates of prescription opioid therapy in 214 Veterans with chronic noncancer pain and an SUD history. Participants completed psychosocial questionnaires and participated in a structured mental health diagnostic interview, and medical diagnoses and opioid pharmacy data were abstracted from their Department of Veterans Affairs electronic medical records. Participants were categorized into three groups based on opioid prescriptions in the past 90 d: no opioid therapy (n = 134), short-term (<90 d) opioid therapy (n = 31), or long-term (>/= 90 d) opioid therapy (n = 49). Relative to participants prescribed no or short-term opioid therapy, participants who were prescribed long-term opioid therapy had a greater number of pain diagnoses; reported higher levels of pain severity, interference, and catastrophizing; and endorsed lower chronic pain self-efficacy. In a multivariate model, number of pain diagnoses and pain interference were associated with a greater likelihood of being prescribed long-term opioid therapy after controlling for demographic and clinical characteristics. Findings highlight the poor pain-related functioning in patients with SUD histories who are prescribed long-term opioid therapy. PMID- 27005462 TI - Duty hours and incidents in flight among commercial airline pilots. AB - INTRODUCTION: Working long duty hours has often been associated with increased risk of incidents and accidents in transport industries. Despite this, information regarding the intermediate relationship between duty hours and incident risk is limited. This study aimed to test a work hours/incident model to identify the interplay of factors contributing to incidents within the aviation industry. METHODS: Nine hundred and fifty-four European-registered commercial airline pilots completed a 30-item survey investigating self-report attitudes and experiences of fatigue. Path analysis was used to test the proposed model. RESULTS: The fit indices indicated this to be a good fit model (chi(2) = 11.066, df = 5, p = 0.05; Comparative Fit Index = 0.991; Normed Fit Index = 0.984; Tucker Lewis Index = 0.962; Root Mean Square of Approximation = 0.036). Highly significant relationships were identified between duty hours and sleep disturbance (r = 0.18, p < 0.001), sleep disturbance and fatigue in the cockpit (r = 0.40, p < 0.001), and fatigue in the cockpit and microsleeps in the cockpit (r = 0.43, p < 0.001). DISCUSSION: A critical pathway from duty hours through to self-reported incidents in flight was identified. Further investigation employing both objective and subjective measures of sleep and fatigue is needed. PMID- 27005463 TI - Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial. AB - PURPOSE: Cancer cachexia is characterized by decreased body weight (mainly lean body mass [LBM]) and negatively impacts quality of life (QOL) and prognosis. Anamorelin (ONO-7643) is a novel selective ghrelin receptor agonist under development for treating cancer cachexia. METHODS: In this double-blind, exploratory phase 2 trial, we examined the efficacy and safety of anamorelin in Japanese patients (n = 181) with non-small cell lung cancer (NSCLC) and cancer cachexia (>=5 % weight loss within the previous 6 months). The participants were randomized into three groups and were administered 50 or 100 mg anamorelin, or placebo, orally every day for 12 weeks. The co-primary endpoints were the changes from baseline over 12 weeks in LBM and handgrip strength (HGS). Secondary endpoints included body weight, QOL, Karnofsky Performance Scale (KPS), and serum biomarkers. RESULTS: The change in LBM over 12 weeks was 0.55 and 1.15 kg in the placebo and 100-mg anamorelin groups, respectively, but the efficacy of anamorelin in HGS was not detected. The changes in body weight were -0.93, 0.54, and 1.77 kg in the placebo, 50-mg anamorelin, and 100-mg anamorelin groups, respectively. Anamorelin (100 mg) significantly improved KPS and QOL-ACD compared with placebo. Administration of anamorelin for 12 weeks was well tolerated. CONCLUSIONS: This phase 2 study showed that 100 mg anamorelin has promising results in improving lean body mass, performance status, and especially, QOL in patients with cancer cachexia. PMID- 27005464 TI - Use of the Needs Evaluation Questionnaire with cancer outpatients. AB - PURPOSE: The Needs Evaluation Questionnaire (NEQ) is a self-administered instrument with 23 dichotomous items that is used both in oncology clinical practice and in research. It was originally developed for use in setting of hospitalization. The aim of the present study was to assess the factor structure of the NEQ in an outpatient oncology sample and to compare the unmet needs of inpatients and outpatients in the Italian context. METHODS: In 6 Italian oncology departments, 783 patients completed the NEQ. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. There were 195 inpatients and 588 outpatients total. RESULTS: Confirmatory factor analysis (CFA) showed that, with outpatients, the NEQ retained the distribution of the items in five main areas previously described with inpatients. Cancer outpatients expressed high percentages of unmet needs primarily concerning "material needs" and "needs for psycho-emotional support." Our survey also suggested that, in addition to the 23 original items, four new items could be tested for specific use with outpatients. CONCLUSIONS: Our findings highlight the importance of establishing routine assessment of unmet needs also in clinical oncology settings different from wards-such as day hospitals, ambulatory rehabilitation, or follow-up ambulatory care-where, at least in the Italian context, the rate of unmet needs is currently considerably high. The NEQ could be an effective tool for this assessment. PMID- 27005465 TI - Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy. AB - PURPOSE: The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM). METHODS: Established HNC quality of life questionnaires and our own MM quality of life questionnaire were sent to 15 HNC patients treated at our institution who reported using MM. Patients are clinically disease free and currently using MM to manage long-term side effects after curative HNC treatment. RESULTS: There was a 100 % response rate. Median time from treatment was 45 months (21-136 months). Most patients smoked marijuana (12 patients), while others reported ingestion (4 patients), vaporizing (3 patients), and use of homemade concentrated oil (1 patient). Six patients reported prior recreational marijuana use before diagnosis. MM provided benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasm, and sticky saliva. CONCLUSIONS: HNC patients report MM use to help with long-term side effects of radiotherapy. PMID- 27005466 TI - Assessing quality of life in a clinical study on heart rehabilitation patients: how well do value sets based on given or experienced health states reflect patients' valuations? AB - BACKGROUND: Quality of life as an endpoint in a clinical study may be sensitive to the value set used to derive a single score. Focusing on patients' actual valuations in a clinical study, we compare different value sets for the EQ-5D-3L and assess how well they reproduce patients' reported results. METHODS: A clinical study comparing inpatient (n = 98) and outpatient (n = 47) rehabilitation of patients after an acute coronary event is re-analyzed. Value sets include: 1. Given health states and time-trade-off valuation (GHS-TTO) rendering economic utilities; 2. Experienced health states and valuation by visual analog scale (EHS-VAS). Valuations are compared with patient-reported VAS rating. Accuracy is assessed by mean absolute error (MAE) and by Pearson's correlation rho. External validity is tested by correlation with established MacNew global scores. Drivers of differences between value sets and VAS are analyzed using repeated measures regression. RESULTS: EHS-VAS had smaller MAEs and higher rho in all patients and in the inpatient group, and correlated best with MacNew global score. Quality-adjusted survival was more accurately reflected by EHS-VAS. Younger, better educated patients reported lower VAS at admission than the EHS-based value set. EHS-based estimates were mostly able to reproduce patient-reported valuation. Economic utility measurement is conceptually different, produced results less strongly related to patients' reports, and resulted in about 20 % longer quality-adjusted survival. CONCLUSION: Decision makers should take into account the impact of choosing value sets on effectiveness results. For transferring the results of heart rehabilitation patients from another country or from another valuation method, the EHS-based value set offers a promising estimation option for those decision makers who prioritize patient-reported valuation. Yet, EHS-based estimates may not fully reflect patient-reported VAS in all situations. PMID- 27005467 TI - Inadequate Helmet Fit Increases Concussion Severity in American High School Football Players. AB - BACKGROUND: There is limited information on the relationship between football helmet fit and concussion severity. HYPOTHESIS: Poor helmet fit may predispose football players to a more severe concussion. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 3. METHODS: Data from concussion injury reports were obtained from the National High School Sports-Related Injury Surveillance System over a 9-year period. Symptoms, duration, and helmet parameters (fit, interior padding) were analyzed for all first-time concussions. RESULTS: Data from 4580 concussions were analyzed. Patients who suffered concussions with a helmet that did not fit properly (3.22%), as determined by an athletic trainer, had higher rates of drowsiness (RR, 1.46; P = 0.005), hyperexcitability (RR, 2.38; P = 0.047), and sensitivity to noise (RR, 1.88; P < 0.001); had more symptoms (5.34 vs 4.54, P = 0.004); and had longer symptom duration (P = 0.04). Athletes with helmets lined with an air bladder had greater rates of sensitivity to light (RR, 1.13; P = 0.02), sensitivity to noise (RR, 1.25; P = 0.009), and longer symptom duration (P = 0.004) compared with foam or gel liners. CONCLUSION: An improperly fitted football helmet is a risk factor for a concussion with more symptoms and of longer duration. Concussions of longer duration are also more common in players with an air bladder-lined helmet. Current high school football rules should mandate supervision and maintenance of helmet fit throughout the season, prior to impact. CLINICAL RELEVANCE: Team physicians, athletic trainers, coaches, and high school officials should ensure proper oversight of helmet fit in high school athletes to decrease concussion severity and duration. PMID- 27005468 TI - IDH mutations in cancer and progress toward development of targeted therapeutics. AB - Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to alpha-ketoglutarate (alphaKG).IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here we provide an overview of the function of normal and mutated IDH, discuss the role of IDH mutations in tumorigenesis and progression and review the key clinical considerations when treating IDH-mutated tumors based on emerging clinical data from mutant IDH1/2 inhibitor trials. IDH1 and IDH2 mutations confer neomorphic activity in the mutant protein, resulting in the conversion of alphaKG to the oncometabolite, D-2-hydroxyglutarate (2-HG). The subsequent accumulation of 2-HG results in epigenetic dysregulation via inhibition of alphaKG-dependent histone and DNA demethylases, and a block in cellular differentiation. There is growing preclinical and clinical evidence suggesting that IDHmutations are involved in neoplasia. Furthermore, preclinical studies assessing small molecule inhibitors of mutant IDH1/2 enzymes have provided proof of concept that this approach decreases intracellular 2-HG levels, reverses epigenetic dysregulation and induces cellular differentiation. Phase I studies of mutant IDH inhibitors are currently ongoing in patients with IDH-mutant hematologic and solid tumors, with early data in hematologic tumors suggesting a manageable safety profile as well as clinical benefit, with a mechanism of action based on differentiation of malignant cells. Inhibition of mutant IDH shows promise as a treatment approach in hematologic malignancies, with further development ongoing in solid tumors and glioma. The mutant IDH inhibitors may have clinical utility both as single agents and in combination strategies that target additional oncogenic pathways. PMID- 27005469 TI - Exploring resilience in nursing and midwifery students: a literature review. AB - AIM: The aim of this study was to explore the concepts of 'resilience' and 'hardiness' in nursing and midwifery students in educational settings and to identify educational interventions to promote resilience. BACKGROUND: Resilience in healthcare professionals has gained increasing attention globally, yet to date resilience and resilience education in nursing and midwifery students remain largely under-researched. DESIGN: An integrative literature review was planned, however, only quantitative evidence was identified therefore, a review of quantitative studies was undertaken using a systematic approach. DATA SOURCES: A comprehensive search was undertaken using Medline, CINAHL, Embase, PsycINFO and Maternity and Infant Care databases January 1980-February 2015. REVIEW METHODS: Data were extracted using a specifically designed form and quality assessed using an appropriate checklist. A narrative summary of findings and statistical outcomes was undertaken. RESULTS: Eight quantitative studies were included. Research relating to resilience and resilience education in nursing and midwifery students is sparse. There is a weak evidence that resilience and hardiness is associated with slightly improved academic performance and decreased burnout. However, studies were heterogeneous in design and limited by poor methodological quality. No study specifically considered student midwives. CONCLUSION: A greater understanding of the theoretical underpinnings of resilience in nursing and midwifery students is essential for the development of educational resources. It is imperative that future research considers both nursing and midwifery training cohorts and should be of strong methodological quality. PMID- 27005470 TI - Sub-classification based specific movement control exercises are superior to general exercise in sub-acute low back pain when both are combined with manual therapy: A randomized controlled trial. AB - BACKGROUND: Clinical guidelines recommend research on sub-groups of patients with low back pain (LBP) but, to date, only few studies have been published. One sub group of LBP is movement control impairment (MCI) and clinical tests to identify this sub-group have been developed. Also, exercises appear to be beneficial for the management of chronic LBP (CLBP), but very little is known about the management of sub-acute LBP. METHODS: A randomized controlled trial (RCT) was conducted to compare the effects of general exercise versus specific movement control exercise (SMCE) on disability and function in patients with MCI within the recurrent sub-acute LBP group. Participants having a MCI attended five treatment sessions of either specific or general exercises. In both groups a short application of manual therapy was applied. The primary outcome was disability, assessed by the Roland-Morris Disability Questionnaire (RMDQ). The measurements were taken at baseline, immediately after the three months intervention and at twelve-month follow-up. RESULTS: Seventy patients met the inclusion criteria and were eligible for the trial. Measurements of 61 patients (SMCE n = 30 and general exercise n = 31) were completed at twelve months. (Drop out rate 12.9 %). Patients in both groups reported significantly less disability (RMDQ) at twelve months follow-up. However, the mean change on the RMDQ between baseline and the twelve-month measurement showed statistically significantly superior improvement for the SMCE group -1.9 points (-3.9 to -0.5) 95 % (CI). The result did not reach the clinically significant three point difference. There was no statistical difference between the groups measured with Oswestry Disability Index (ODI). CONCLUSION: For subjects with non-specific recurrent sub-acute LBP and MCI an intervention consisting of SMCE and manual therapy combined may be superior to general exercise combined with manual therapy. TRIAL REGISTRATION: The study protocol registration number is ISRCTN48684087 . It was registered retrospectively 18th Jan 2012. PMID- 27005471 TI - Comparative study of indirect immunofluorescence, enzyme-linked immunosorbent assay, and the Tzanck smear test for the diagnosis of pemphigus. AB - BACKGROUND: Pemphigus is one of the potentially fatal autoimmune blistering diseases. An early and accurate diagnosis is important for prognosis and therapy. It may be difficult to diagnosis based on clinical grounds alone. Direct and indirect immunofluorescence, enzyme-linked immunosorbent assay, the Tzanck smear test, or histopathology are all available for the diagnosis of pemphigus. However, there are no generally accepted diagnostic criteria for the diagnosis of this condition at present. OBJECTIVE: To evaluate the diagnostic value of indirect immunofluorescence, enzyme-linked immunosorbent assay, and the Tzanck smear test for the diagnosis of pemphigus in dental clinics. METHODS: A single center retrospective study was conducted, and the clinical data of 33 patients with pemphigus and 61 controls were collected and analyzed from the Department of Oral Medicine, Peking University School of Stomatology, during 2010-2014. The sensitivities and specificities of indirect immunofluorescence, enzyme-linked immunosorbent assay, and the Tzanck smear test were calculated and compared in two groups. RESULTS: Sensitivities for the Tzanck smear test, indirect immunofluorescence, and enzyme-linked immunosorbent assay were 96.7%, 84.8%, and 84.8%, respectively, whereas the specificities of these tests were 60%, 91.8%, and 96.7%, respectively. The serial tests for the Tzanck smear test and enzyme linked immunosorbent assay showed 82% sensitivity and 98.7% specificity. CONCLUSIONS: The serial test for the Tzanck smear test and enzyme-linked immunosorbent assay may represent a simple, rapid, and reliable way to definitive diagnosis of pemphigus. It is recommended as a common test for the diagnosis of pemphigus in dental clinics. PMID- 27005472 TI - Using Jupiter's gravitational field to probe the Jovian convective dynamo. AB - Convective motion in the deep metallic hydrogen region of Jupiter is believed to generate its magnetic field, the strongest in the solar system. The amplitude, structure and depth of the convective motion are unknown. A promising way of probing the Jovian convective dynamo is to measure its effect on the external gravitational field, a task to be soon undertaken by the Juno spacecraft. We calculate the gravitational signature of non-axisymmetric convective motion in the Jovian metallic hydrogen region and show that with sufficiently accurate measurements it can reveal the nature of the deep convection. PMID- 27005473 TI - Molecular Characterization of Giardia duodenalis in Children in Kenya. AB - BACKGROUND: Giardia duodenalis is an important intestinal protozoan in humans worldwide with high infection rates occurring in densely populated and low resource settings. The parasite has been recorded to cause diarrhea in children. This study was carried out to identify G. duodenalis assemblages and sub assemblages in children presenting with diarrhea in Kenya. METHODS: A total of 2112 faecal samples were collected from children aged <= 5 years and screened for the presence of Giardia cysts using microscopy. A total of 96 (4.5%) samples were identified as Giardia positive samples and were genotyped using glutamate dehydrogenase (gdh), triose phosphate isomerase (tpi) and beta-giardin loci. RESULTS: The three markers successfully genotyped 72 isolates and grouped 2 (1.4) isolates as Assemblage A, 64 (88.9) as Assemblage B and 7 (9.7%) consisted of mixed infections with assemblage A and B. A further analysis of 50 isolates using GDH Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR RFLP) categorized 2 assemblage A isolates as sub-assemblage AII while 6 and 14 assemblage B isolates were categorized into sub-assemblage BIII and BIV respectively. A mixed infection with sub-assemblage BIII and BIV was recorded in 28 isolates. Over half (55.6%) of Giardia infections were recorded among the children between 13 to 48 months old. CONCLUSION: This paper reports the first data on the assemblages and sub-assemblages of Giardia duodenalis in children representing with diarrhea in Kenya. PMID- 27005474 TI - Variation in sequences containing microsatellite motifs in the perennial biomass and forage grass, Phalaris arundinacea (Poaceae). AB - Forty three microsatellite markers were developed for further genetic characterisation of a forage and biomass grass crop, for which genomic resources are currently scarce. The microsatellite markers were developed from a normalized EST-SSR library. All of the 43 markers gave a clear banding pattern on 3% Metaphor agarose gels. Eight selected SSR markers were tested in detail for polymorphism across eleven DNA samples of large geographic distribution across Europe. The new set of 43 SSR markers will help future research to characterise the genetic structure and diversity of Phalaris arundinacea, with a potential to further understand its invasive character in North American wetlands, as well as aid in breeding work for desired biomass and forage traits. P. arundinacea is particularly valued in the northern latitude as a crop with high biomass potential, even more so on marginal lands. PMID- 27005475 TI - Beta-blocker treatment of caffeine-induced tachydysrhythmias. PMID- 27005476 TI - The rich get richer, the poor get even: Perceived socioeconomic position influences micro-social distributions of wealth. AB - Economic inequality has a robust negative effect on a range of important societal outcomes, including health, wellbeing, and education. Yet, it remains insufficiently understood why, how, and by whom unequal systems tend to be perpetuated. In two studies we examine whether psychological mindsets adopted by the wealthy and the poor in their micro-social transactions act to perpetuate or challenge inequality. We hypothesized that occupying a wealthier socioeconomic position promotes the pursuit of self-interest and contributes to inequality maintenance; poorer socioeconomic position, on the other hand, should promote the pursuit of fairness and equality restoration. In Study 1, participants completed an ultimatum game as proposers after being primed to believe they are wealthier or poorer, offering money to either poor or wealthy responders. As expected, the wealthy pursued their self-interest and the net effect of this behavior contributes to the maintenance of inequality. Conversely, the poor pursued fairness and the net effect of this behavior challenges inequality. In Study 2, participants were responders deciding whether to accept or reject unfair distributions. Compared to the wealthier, the poorer challenged inequality by rejecting unequal offers. The links between micro-social processes and macro societal inequality are discussed. PMID- 27005477 TI - Reproductive biology of Urotrygon microphthalmum (Batoidea: Urotrygonidae) from north-eastern Brazil, tropical west Atlantic Ocean. AB - The reproductive biology of Urotrygon microphthalmum was studied based on specimens caught as by-catch in shrimp (Litopenaeus schmitti, Xiphopenaeus kroyeri, Farfantepenaeus subtilis and Farfantepenaeus brasiliensis) fishing operations between March 2010 and March 2012 on the coast of Pernambuco, Brazil. Females reached a larger total length (LT ) and total body mass (MT ) (298 mm and 148 g) than males (250 mm and 90 g). Length at maturity was estimated to be 188 and 199 mm LT for males and females. Uterine fecundity ranged from one to four embryos (mean +/- s.d.: 1.85 +/- 0.45). Size at birth was estimated to be 105 mm LT . Gestation lasted between 4 and 5 months. The reproductive cycle of U. microphthalmum is hypothesized to be asynchronous and biannual. PMID- 27005478 TI - A randomised, double-blinded, placebo-controlled clinical study on intra articular hyaluronan treatment in equine lameness originating from the metacarpophalangeal joint. AB - BACKGROUND: Intra-articular inflammation resulting in lameness is a common health problem in horses. Exogenous intra-articular hyaluronic acid has been shown to provide an analgesic effect and reduce pain in equine and human osteoarthritis. High molecular weight non-animal stabilized hyaluronic acid (NASHA) has gained popularity in the treatment of human arthritic conditions due to its long-acting pain-relieving effects. The aim of this study was to compare the response to treatment of lameness localized in the equine metacarpophalangeal joint injected with non-animal stabilized hyaluronic acid (NASHA) and placebo (saline). Twenty seven clinically lame horses with a positive response to diagnostic intra articular anaesthesia of the metacarpophalangeal joint and with no, or at most mild, radiographic changes in this joint were included in the study. Horses in the treatment group (n = 14) received 3 mL of a NASHA product intra-articularly, and those in the placebo group (n = 13) received an equivalent volume of sterile 0.9% saline solution. RESULTS: The change in the lameness score did not significantly differ between NASHA and placebo groups (P = 0.94). Scores in the flexion test improved more in the NASHA group compared with placebo (P = 0.01). The changes in effusion and pain in flexion were similar (P = 0.94 and P = 0.27, respectively) when NASHA and placebo groups were compared. A telephone interview follow-up of the owners three months post-treatment revealed that 14 of the 21 horses (67%) were able to perform at their previous level of exercise. CONCLUSIONS: In the present study, a single IA NASHA injection was not better than a single saline injection for reducing lameness in horses with synovitis or mild osteoarthritis. However, the results of this study indicate that IA NASHA may have some beneficial effects in modifying mild clinical signs but more research is needed to evaluate whether the positive effect documented ie. reduced response in the flexion test is a true treatment effect. PMID- 27005479 TI - Idiopathic Acquired Osteosclerosis in a Middle-Aged Woman With Systemic Lupus Erythematosus. AB - Widely distributed osteosclerosis is an unusual radiographic finding with multiple causes. A 42-year-old premenopausal Spanish woman gradually acquired dense bone diffusely affecting her axial skeleton and focally affecting her proximal long bones. Systemic lupus erythematosus (SLE) diagnosed in adolescence had been well controlled. She had not fractured or received antiresorptive therapy, and she was hepatitis C virus antibody negative. Family members had low bone mass. Lumbar spine bone mineral density (BMD) measured by dual-photon absorptiometry (DPA) at age 17 years, while receiving glucocorticoids, was 79% the average value of age-matched controls. From ages 30 to 37 years, dual-energy X-ray absorptiometry (DXA) BMD Z-scores steadily increased in her lumbar spine from +3.8 to +7.9, and in her femoral neck from -1.4 to -0.7. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) <20 ng/mL, and parathyroid hormone (PTH) sometimes slightly increased. Her reduced estimated glomerular filtration rate (eGFR) was 38 to 55 mL/min. Hypocalciuria likely reflected positive mineral balance. During increasing BMD, turnover markers (serum bone-specific alkaline phosphatase [ALP], procollagen type 1 N propeptide [P1NP], osteocalcin [OCN], and carboxy-terminal cross-linking telopeptide of type 1 collagen [CTx], and urinary amino-terminal cross-linking telopeptide of type 1 collagen [NTx and CTx]) were 1.6- to 2.8-fold above the reference limits. Those of bone formation seemed increased more than those of resorption. FGF-23 was slightly elevated, perhaps from kidney disease. Serum osteoprotegerin (OPG) and TGFbeta1 levels were normal, but sclerostin (SOST) and receptor activator of nuclear factor kappa-B ligand (RANKL) were elevated. Serum multiplex biomarker profiling confirmed a high level of SOST and RANKL, whereas Dickkopf-1 (DKK-1) seemed low. Matrix metalloproteinases-3 (MMP-3) and -7 (MMP-7) were elevated. Iliac crest biopsy revealed tetracycline labels, no distinction between thick trabeculae and cortical bone, absence of peritrabecular fibrosis, few osteoclasts, and no mastocytosis. Then, for the past 3 years, BMD Z-scores steadily decreased. Skeletal fluorosis, mastocytosis, myelofibrosis, hepatitis C associated osteosclerosis, multiple myeloma, and aberrant phosphate homeostasis did not explain her osteosclerosis. Mutation analysis of the LRP5, LRP4, SOST, and osteopetrosis genes was negative. Microarray showed no notable copy number variation. Perhaps her osteosclerosis reflected an interval of autoimmune mediated resistance to SOST and/or RANKL. (c) 2016 American Society for Bone and Mineral Research. PMID- 27005480 TI - Comparison of two preventive interventions on dental caries among children in Democratic People's Republic of Korea. AB - OBJECTIVES: The aim was to compare the change in dental caries status in two different intervention groups of the Children's Oral Health Promotion Programme (COHPP). METHODS: A longitudinal study among 500 children who had participated into the COHPP for 6 years was conducted in Pyongyang, Democratic People's Republic of Korea (DPRK). Children in Group I received intensified school-based intervention and were clinically examined at the age of 7 years in 2007 (n = 250), 10 years in 2010 (n = 250) and 13 years in 2013 (n = 242). Children in Group II (n = 250) joined the programme at the age of 4 years in kindergarten in 2007, were provided with early preschool-based intervention and were clinically examined at the age of 7 years in 2010 and 10 years in 2013. RESULTS: Both the prevalence and the mean number of dt + DT decreased significantly in both groups during the follow-up. This was due to decrease in the number of dt, whereas the number of DT remained relatively constant. Poisson regression showed that the association between the group status and the change in the number of dt + DT was statistically significant when adjusted for gender but disappeared when the school was included in the analysis. CONCLUSIONS: The decrease in dental caries may be partly due to the exfoliation of deciduous teeth and dental treatment received. However, the study gave some reference emphasizing the early starting of the prevention. PMID- 27005481 TI - Suppression of spin-exciton state in hole overdoped iron-based superconductors. AB - The mechanism of Cooper pair formation in iron-based superconductors remains a controversial topic. The main question is whether spin or orbital fluctuations are responsible for the pairing mechanism. To solve this problem, a crucial clue can be obtained by examining the remarkable enhancement of magnetic neutron scattering signals appearing in a superconducting phase. The enhancement is called spin resonance for a spin fluctuation model, in which their energy is restricted below twice the superconducting gap value (2Deltas), whereas larger energies are possible in other models such as an orbital fluctuation model. Here we report the doping dependence of low-energy magnetic excitation spectra in Ba1 xKxFe2As2 for 0.5 < x < 0.84 studied by inelastic neutron scattering. We find that the behavior of the spin resonance dramatically changes from optimum to overdoped regions. Strong resonance peaks are observed clearly below 2Deltas in the optimum doping region, while they are absent in the overdoped region. Instead, there is a transfer of spectral weight from energies below 2Deltas to higher energies, peaking at values of 3Deltas for x = 0.84. These results suggest a reduced impact of magnetism on Cooper pair formation in the overdoped region. PMID- 27005482 TI - Albumin-bilirubin versus Child-Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma. AB - BACKGROUND: The Child-Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin-bilirubin (ALBI) score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent. METHODS: Consecutive patients who underwent liver resection with curative intent for HCC between January 2007 and July 2013 were included in this retrospective study. The performance of the ALBI score in predicting postoperative liver failure (PHLF) and long-term survival was compared with that of the CP score. RESULTS: A total of 1242 patients were enrolled. Of these, 166 (13.4 per cent) experienced PHLF. The area under the receiver operating characteristic (ROC) curve of the ALBI score for predicting PHLF was greater than that of the CP score (0.723 versus 0.607; P < 0.001). Similar to findings for CP grade, the incidence and severity of PHLF increased with increasing ALBI grade. The ALBI grade stratified patients into at least two distinct overall survival cohorts (P < 0.001), whereas the CP grade did not. The ALBI grade also classified patients with CP grade A disease into two distinct overall survival cohorts (P < 0.001), and overall survival rates in the group with poorer survival were similar to those in the majority of patients with CP grade B disease. Both CP and ALBI scores had low power in predicting disease-free survival. CONCLUSION: The ALBI grade predicted PHLF and overall survival in patients with HCC undergoing liver resection with curative intent more accurately than the CP grade. PMID- 27005483 TI - Effect of Na3FeF6 catalyst on the hydrogen storage properties of MgH2. AB - The effects of Na3FeF6 catalyst on the hydrogen storage properties of MgH2 have been studied for the first time. The results showed that for the MgH2 sample doped with 10 wt% Na3FeF6, the onset dehydrogenation temperature decreased to 255 degrees C, which was 100 degrees C and 162 degrees C lower than those of the as-milled and as-received MgH2 sample, respectively. The re/dehydrogenation kinetics were also significantly enhanced compared to the un-doped MgH2. The absorption kinetics showed that the as-milled MgH2 only absorbed 3.0 wt% of hydrogen at 320 degrees C in 2 min of rehydrogenation, but about 3.6 wt% of hydrogen was absorbed within the same period of time after 10 wt% Na3FeF6 was added to MgH2. The desorption kinetics showed that the MgH2 + 10 wt% Na3FeF6 sample could desorb about 3.8 wt% of hydrogen in 10 min at 320 degrees C. In contrast, the un-doped MgH2 sample desorbed only 0.2 wt% of hydrogen in the same period of time. The activation energy for the decomposition of the as-milled MgH2 was 167.0 kJ mol(-1), and this value decreased to 75.0 kJ mol(-1) after the addition of 10 wt% Na3FeF6 (a reduction by about 92.0 kJ mol(-1)). It is believed that the in situ formation of the active species of NaMgF3, NaF and Fe during the heating process could enhance the hydrogen storage properties of MgH2, due to the catalytic effects of these new species. PMID- 27005484 TI - Overcoming foetal motion using interactive real-time magnetic resonance imaging. AB - OBJECTIVE: Foetal MRI has become an established image modality in the prenatal diagnosis of CNS anomalies, but image quality can be severely affected by foetal movements. The objective was to overcome these inherent motion problems by applying interactive real-time MRI and to evaluate the diagnostic usefulness of the applied real-time MRI sequence in relation to standard protocols. METHODS: Ten healthy foetuses (gestation week 21.3 +/- 0.5) were scanned using a system, which allowed visual feedback and interactive slice positioning in real time. The data were compared to a control group of 14 healthy foetuses (gestation week 21.0 +/- 0.8) who had previously been scanned using standard MRI. Comparisons were carried out by two radiologists with regard to cerebral anthropometric sizes, presence of important brain structures, degree of movement, clinical image value, image quality and ability to obtain correct slice planes. RESULTS: Two out of eight anthropometric sizes were statistically different between the two groups. Representation of cerebral structures was found in 70-100% in the real-time group. No statistically differences were found in clinical image value and image quality. The mean ability to obtain optimal slice planes was higher in the real time group, but it was not significant. CONCLUSION: Imaging of the foetal brain using the proposed interactive real-time MRI system is a promising alternative to traditional foetal MRI for anthropometrics or as a supplement for the representation of foetal brain structures in cases in which foetal motion causes challenges in relation to obtaining optimal slice planes using conventional MRI techniques. PMID- 27005485 TI - Identification of YPL014W (Cip1) as a novel negative regulator of cyclin dependent kinase in Saccharomyces cerevisiae. AB - Cyclin-dependent kinases drive cell division cycle progression in eukaryotic cells. In the model eukaryotic organism Saccharomyces cerevisiae (budding yeast), a single cyclin-dependent kinase, Cdk1, is essential and sufficient to drive the cell cycle. Misregulated CDK activity induces unscheduled proliferation as well as genomic instability, which are hallmarks of the cancer. Here, we report a novel Cdk1-interacting protein, YPL014W, which we name Cip1 (for Cdk1-interacting protein 1). Our results show that Cip1 specifically interacts with G1 /S-phase Cln2-Cdk1 complex but not with S-phase Clb5-Cdk1 or M-phase Clb2-Cdk1 complexes. Also Cip1 phosphorylation is cell cycle regulated in a S-phase Cdk1-dependent manner. Over-expression of Cip1 blocks cell cycle progression in G1 and stabilizes the S-phase Cdk1 inhibitor Sic1 in vivo. In addition, disruption of CIP1 (cip1Delta) leads to faster G1 /S-phase transition compared to wild-type cells. Moreover, Cip1 inhibits Cln2-CDK activity both in vivo and in vitro. Our finding proves Cip1 as a novel negative regulator of cyclin-dependent kinase in S. cerevisiae. PMID- 27005486 TI - Endocytic adaptors Arh and Dab2 control homeostasis of circulatory cholesterol. AB - High serum cholesterol (hypercholesterolemia) strongly associates with cardiovascular diseases as the atherogenic LDLs promote atheroma development in arteries (atherosclerosis). LDL clearance from the circulation by LDL receptor (LDLR)-mediated endocytosis by hepatic and peripheral tissues and subsequent feedback regulation of endogenous synthesis of cholesterol is a key determinant of serum LDL level. Human mutation analysis revealed that autosomal recessive hypercholesterolemia (ARH), an LDLR endocytic adaptor, perturbs LDLR function and thus impacts serum cholesterol levels. In our genetic analysis of mutant mice, we found that deletion of another LDLR endocytic adaptor, Disabled-2 (Dab2), only slightly affected serum cholesterol levels. However, elimination of both arh and dab2 genes in mice resulted in profound hypercholesterolemia similar to that resulting from ldlr homozygous deletion. In the liver, Dab2 is expressed in sinusoid endothelial cells but not in hepatocytes. When deleting both Dab2 and Arh, HMG-CoA reductase level increased to the level similar to that of ldlr knockout. Thus, in the absence of Arh, Dab2 in liver endothelial cells regulates cholesterol synthesis in hepatocytes. We conclude that the combination of Arh and Dab2 is responsible for the majority of adaptor function in LDLR endocytosis and LDLR-mediated cholesterol homeostasis. PMID- 27005487 TI - Histopathology Image Analysis in Two Long-Term Animal Experiments with Helical Flow Total Artificial Heart. AB - Histopathological analysis can provide important information in long-term experiments with total artificial heart (TAH). Recently, a new type of blood pump, the helical flow total artificial heart (HF-TAH) was developed. This study aimed to investigate the changes in selected vital organs in animal experiments with implanted HF-TAH. Samples from lung, liver, and kidneys from two female goats (No. 1301 and No. 1304) with implanted HF-TAH were analyzed. Tissue samples were fixed in 10% formaldehyde and 4 um thick transverse sections were stained with hematoxylin-eosin (HE). Additional staining was done for detection of connective tissue (Masson-Goldner stain) and for detection of iron (hemosiderin) deposits (Perls stain). Sections were scanned at 100* and 500* magnification with a light microscope. Experiment no. 1301 survived 100 days (cause of termination was heavy damage of the right pump); experimental goat no.1304 survived 68 days and was sacrificed due to severe right hydrodynamic bearing malfunction. Histopathological analysis of liver samples proved signs of chronic venostasis with limited focal necrotic zones. Dilated tubules, proteinaceous material in tubular lumen, and hemosiderin deposits were detected in kidney samples. Contamination of the organs by embolized micro-particles was suspected at the autopsy after discovery of visible damage (scratches) of the pump impeller surface (made from titanium alloy) in both experiments. Sporadic deposits of foreign micro-particles (presumably titanium) were observed in most of the analyzed parenchymal organs. However, the described deposits were not in direct connection with inflammatory reactions in the analyzed tissues. Histopathological analysis showed the presence of minimal contamination of the lung, kidney, and liver tissue samples by foreign material (titanium very likely). The analysis showed only limited pathological changes, especially in liver and kidneys, which might be attributed to the influence of artificial perfusion often observed in chronic TAH experiments. PMID- 27005488 TI - The Perilous Road from HIV Diagnosis in the Hospital to Viral Suppression in the Outpatient Clinic. AB - The HIV care continuum has received considerable attention in recent years, however, few care continua focus on the population of patients who are diagnosed during an inpatient hospital admission. We aimed to describe the HIV care continuum for patients newly diagnosed during hospitalization through 24-month follow-up. A retrospective chart review of HIV patients diagnosed at Grady Memorial Hospital from 2011 to 2012 was performed and records were matched to Georgia Department of Public Health HIV/AIDS surveillance data. Descriptive statistics and statistical tests of independence were utilized. Ninety-four new diagnoses were confirmed during the 2-year study period. Median age was 43 years (interquartile range [IQR] 30-51), 77% were male, 72% were non-Hispanic Black, 31% were men who have sex with men (MSM), and 77% were uninsured. Median CD4 count at diagnosis was 134 cells/MUL (IQR 30-307). Eighty-four percent received their diagnosis before hospital discharge, 68% linked to care by 90 days, 73% were retained for 12 months, 48% were virologically suppressed by 12 months, 58% were retained for 24 continuous months, and 38% achieved continuous viral suppression (VS) during the initial 24 months after diagnosis. Late diagnosis is a persistent problem in hospitalized patients. Despite relative success with linkage to care and 12-month retention in care, a minority of patients maintained retention and VS for 24 continuous months. PMID- 27005489 TI - Fluorescent cross-linked supramolecular polymers constructed from a novel self complementary AABB-type heteromultitopic monomer. AB - A novel AABB-type heteromultitopic monomer (), having a self-complementary perpendicular structure, could solely self-assemble to fluorescent cross-linked supramolecular polymers. Interestingly, the supramolecular gel film shows a sensitive fluorescence change on exposure to acid and base vapor, endowing this system with a potential application in gas detection. PMID- 27005490 TI - Success Rates for Notification of Enrollment in Exception From Informed Consent Clinical Trials. AB - OBJECTIVES: Exception from informed consent (EFIC) for research in emergency settings requires investigators to notify enrolled subjects, family members, or legally authorized representatives about inclusion in the study. We examined the success rate of a notification strategy including mail services for subjects enrolled in EFIC trials. METHODS: We describe notification attempts for subjects in three out-of-hospital cardiac arrest clinical trials in both urban and rural areas around Pittsburgh, Pennsylvania, between the years 2000 and 2014. We examined the time required to notify subjects and the success of contacting subjects or their representatives when notified in person (if alive), by mail (if alive and unable to reach in person), or by mail (if the subject was deceased). We characterized comments received from subjects or their representatives as positive, neutral, or negative. RESULTS: We attempted notification on a total of 1,912 subjects, 1,762 by mail, and 163 in person. Of these, 1,767 (92%) notification forms were successfully delivered, and 431 (24%) were signed and returned. Only 16 subjects or representatives (0.91%) requested to withdraw from the study. In-person notifications were more likely to be signed than mailed notifications (69% vs. 20%; p < 0.001). A total of 3.2% of recipients contacted investigators by phone or letter in response to notifications, but only five recipients expressed negative attitudes toward the trial. Ninety percent of subjects were notified within 35 days of the incident. Time to notification was shorter for in person (median = 5 days, interquartile range [IQR] = 2 to 10 days) than for deceased and mailed (11 days, IQR = 8 to 14 days) or alive and mailed (20 days, IQR = 14 to 29 days). CONCLUSIONS: It is possible to successfully notify recipients of enrollment in a study using EFIC over 90% of the time within 35 days, although only 24% of recipients will sign and return a form. Fewer than 1% of subjects withdraw from the study, and fewer than 5% contact investigators, usually for neutral reasons. PMID- 27005491 TI - Protein Quality in the First Thousand Days of Life. AB - The aim of this article is to provide an overview of the role of protein quality within the first 1000 days of life. The article outlines the importance of protein quality in pregnancy and early growth and examines the potential of high quality protein in prevention of stunting and treatment of severe and moderate acute malnutrition. The article also provides a summary of the recent changes in protein quality evaluation and the development of a new index, the Digestibility Corrected Amino Acid Score, examining the opportunities and challenges this new methodology presents in assessing protein quality. PMID- 27005492 TI - Delivering Improved Nutrition: Dairy Ingredients in Food Aid Products. AB - The United States has a long history of food assistance for humanitarian need. The Food for Peace Act of 1954 established the United States' permanent food assistance program which has fed over 3 billion people in 150 countries worldwide through thousands of partner organizations. In 60 years, the program has evolved and will continue to do so. Recently, the program has gone from a focus on quantity of food shipped to quality food assistance from improved products, programs, and processes to effectively meet the needs of different vulnerable groups. The current debate focuses on the appropriateness of using fortified blended foods to prevent and treat malnutrition during the first 1000 days of life. Dairy ingredients have been at the center of this debate; they were included initially in fortified blended, removed in the 1980s, and now reincorporated into fortified therapeutic and supplemental foods. Improved quality food baskets and effective nutrition programming to prevent and treat malnutrition were developed through multisectoral collaboration between government and nongovernment organizations. The US Agency for International Development has focused on improving nutrition through development programs often tied to health, education, and agriculture. The years since 2008 have been a particularly intense period for improvement. The Food Aid Quality Review was established to update current food aid programming products, program implementation, cost-effectiveness, and interagency processes. Trials are underway to harmonize the areas of multisectoral nutrition programming and gather more evidence on the effects of dairy ingredients in food aid products. PMID- 27005493 TI - Vectorial strain gauge method using single flexible orthogonal polydimethylsiloxane gratings. AB - A vectorial strain gauge method using a single sensing element is reported based on the double-sided polydimethylsiloxane (PDMS) Fraunhofer diffraction gratings structures. Using O2 plasma treatment steps, orthogonal wrinkled gratings were fabricated on both sides of a pre-strained PDMS film. Diffracted laser spots from this structure have been used to experimentally demonstrate, that any applied strain can be quantitatively characterized in both the x and y directions with an error of less than 0.6% and with a gauge factor of approximately 10. This simple and low cost technology which is completely different from the traditional vectorial strain gauge method, can be applied to surface vectorial strain measurement and multi-axis integrated mechanical sensors. PMID- 27005494 TI - Carbon nanotube-amorphous silicon hybrid solar cell with improved conversion efficiency. AB - We report a hybrid solar cell based on single walled carbon nanotubes (SWNTs) interfaced with amorphous silicon (a-Si). The high quality carbon nanotube network was dry transferred onto intrinsic a-Si forming Schottky junction for metallic SWNT bundles and heterojunctions for semiconducting SWNT bundles. The nanotube chemical doping and a-Si surface treatment minimized the hysteresis effect in current-voltage characteristics allowing an increase in the conversion efficiency to 1.5% under an air mass 1.5 solar spectrum simulator. We demonstrated that the thin SWNT film is able to replace a simultaneously p-doped a-Si layer and transparent conductive electrode in conventional amorphous silicon thin film photovoltaics. PMID- 27005495 TI - Biological evaluation and molecular docking of some chromenyl-derivatives as potential antimicrobial agents. AB - Various thiosemicarbazones (TSCs) and their heterocyclic thiadiazolines (TDZ) possess important biological effects. In addition, chromenyl derivatives exhibit a wide range of pharmacological activities. Based on these findings and as a continuation of our research on nitrogen and sulfur containing compounds, we investigated a series of previously reported chromenyl-TSCs (1a-j) and chromenyl TDZs (2a-j) for their in vitro antimicrobial activities against two bacterial and four fungal strains. MIC and MBC/MFC (ug/mL) values of these compounds were evaluated and compared to those of Spectinomycin, Moxifloxacin and Fluconazole, used as reference drugs. For a better understanding of the drug-receptor interactions, all the compounds were further subjected to molecular docking against four targets that were chosen based on the specific mechanism of action of the reference drugs used in the antimicrobial screening. All compounds tested showed equal or higher antibacterial/antifungal activities relative to the used reference drugs. In silico studies (molecular docking) revealed that all the investigated compounds showed good binding energies towards four receptor protein targets and supported their antimicrobial properties. PMID- 27005496 TI - Clinical research on postoperative efficacy and related factors of early simulation hyperbaric oxygen therapy for severe craniocerebral injury. AB - In order to discuss the clinical efficacy of simulation hyperbaric oxygen therapy (HBOT) for severe craniocerebral injury and analyze the related factors of it, 108 patients who transferred to our department during December 2010 - December 2014 for ventilator treatment after operation of severe craniocerebral injury were taken as the subjects of the study. These patients were divided into conventional treatment group and simulation hyperbaric oxygen therapy group to contrast the curative effects. At the meantime, GOS score and length of stay in intensive care unit (ICU) of two groups 6 months after treatment, as well as changes in the indexes of the HBO group during treatment were performed statistical analysis. Then factors affecting prognosis of simulation HBOT were performed regression analysis and principal component analysis. The results showed that when compared to the control group, differences in cases with four GOS score and one GOS score in the treatment group were significant (p<0.05). Jugular venous oxygen saturation (SjvO2), jugular bulb oxygen partial pressure (PjO2), arterial partial pressure of oxygen (PaO2) and arterial oxygen saturation (SaO2) of the simulation HBO group before the first time treatment on the first day and after the first time treatment on the third day were significantly increased, with statistical significance (p<0.05); serum lactic acid (Lac) and blood glucose (Glu) decreased significantly (p<0.05). Prior to and during the first treatment on the first day, jugular bulb pressure (Pj) and central venous pressure (CVP) had no significant difference (p>0.05). Regression analysis indicated that factors affecting prognosis included cerebral contusion, coronary heart disease, hydrocephalus and tracheotomy. Principal component analysis found the factors were hydrocephalus, coronary heart disease, tracheotomy, cerebral contusion, cerebral infarction and glasgow coma scale (GCS) before treatment. Therefore, stimulation HBOT can significantly improve the prognosis of patients with severe craniocerebral injury. Paying attention to risk factors in clinics and giving timely interventional treatment can reduce morbidity and mortality in patients. PMID- 27005497 TI - Diagnosis and clinical observation of lactose-free milk powder on treatment of neonatal diarrhea. AB - Neonatal lactose intolerance syndrome is a series of digestive system symptoms caused by the lack of lactase, and could not fully digest the lactose in breast milk or cow milk. Lactose is one of the disaccharides mainly existed in mammalian milk. Lactose content in breast milk is 7.2g/100ml, cow milk is 4.7g/100ml. Dairy products are the main energy sources for the newborn, and lactose provides 20% energy for infants. During the growth of the newborn, lactose not only play a significant role in energy supply, but also involve in the development of the brain growing. This study mainly studied the lactose development features, the reasons for lactose intolerance, and the measures to treat lactose deficiency. PMID- 27005498 TI - The incidence of infants with rotavirus enteritis combined with lactose intolerance. AB - This study was to research the incidence of infants with rotavirus enteritis combined with lactose intolerance and the clinical effect of low lactose milk powder for infantile rotavirus enteritis with lactose intolerance. The control groups were 126 cases of infants with diarrhea randomly collected from our hospital at the same period, which their rotavirus detection was negative. The observation group was 185 cases of infants with rotavirus, which was tested to be positive. Through the urine galactose determination, 62 cases of the control group were positive and 124 cases of the observation group were positive. Then 124 cases of infants with rotavirus combined with lactose intolerance were randomly divided into two groups. 60 cases in the control group were given rehydration, correction of acidosis, oral smecta, Intestinal probiotics and other conventional treatment, then continued to the original feeding method. While, 64 cases in the treatment group, on the basis of routine treatment, applied the low lactose milk feeding. To observe the total effective rate for the two groups. The incidence of lactose intolerance in children with rotavirus enteritis (67.03%) was significantly higher than that of children with diarrhea (49.2%), which was tested to be negative. And the difference was statistically significant (p<0.5). In the aspect of reducing the frequency of diarrhea, and diarrhea stool forming time, the treatment group has the obvious superiority. The total effective rate was 95.4% for treatment group, which was higher than that in the control group (76.7%), the difference was statistically significant (P<0.05). CONCLUSION: Infants with rotavirus enteritis was easier to merge with lactose intolerance. The low lactose milk powder could improve the therapeutic effectively and could reduce the duration of disease, and restored to normal diet for 2 weeks feeding time. PMID- 27005499 TI - Antioxidant evaluation for Urtica urens, Rumex cyprius and Borago officinalis edible wild plants in Palestine. AB - Natural plants products are one of the famous and commonly utilized remedies used in fighting diseases. This study was conducted to evaluate antioxidant activity of plants commonly used in Palestine (Urtica urens, Rumex cyprius and Borago officinalis). Free radical scavenging activity method was evaluated by using 2,2 diphenyl-1-picryl-hydrazyl-hydrate. The result show that the overall antioxidant activity of Rumex cyprius was the highest among the plants, followed by Urtica urens, and Borago officinalis; respectively. The (IC(50)) values of the methanolic extracts were 29.70+/-0.60MUg/ml, 5.07+/-0.49MUg/ml, 39.92+/- 0.52 MUg/ml for Urtica urens, Rumex cyprius and Borago officinalis respectively. The results of this study revealed that these edible plants have high antioxidant activity and therefore they can provide natural sources of antioxidants and can be useful in preventing various diseases including cancer. These exhibited properties propose that such plants extracts can possibly be used as natural preservatives in the food and pharmaceutical industries and further characterization of Rumex cyprius constituents is needed. PMID- 27005500 TI - Causes and nursing countermeasures in pediatric PICC catheter complications. AB - To analyze the complications and nursing countermeasures of PICC (Peripherally Inserted Central Catheter) catheters using children PICC catheter technique 40 cases, complications were observed, and analyze the original causes, in order to propose a solution. There were 10 cases of catheter blockage, 5 cases of catheter infection, 6 cases of phlebitis, 5 cases of puncture difficulties, 2 cases of poor feeding tube, 2 cases of bleeding puncture site with the continuous exploration and research of nursing intervention, the production of clinical complications from PICC has been used in children were greatly reduced. PMID- 27005501 TI - Short Communication: Rheological properties of blood serum of rats after irradiation with different gamma radiation doses in vivo. AB - The blood serum rheological properties open the door to find suitable radio protectors and convenient therapy for many cases of radiation exposure. The present study aimed to investigate the rheological properties of rat blood serum at wide range of shear rates after whole body irradiation with different gamma radiation doses in vivo. Healthy male rats were divided into five groups; one control group and 4 irradiated groups. The irradiation process was carried out using Co60 source with dose rate of 0.883cG/sec. Several rheological parameters were measured using Brookfield LVDV-III Programmable rheometer. A significant increase in viscosity and shear stress was observed with 25 and 50Gy corresponding to each shear rate compared with the control; while a significant decrease observed with 75 and 100Gy. The viscosity exhibited a Non-Newtonian behaviour with the shear rate while shear stress values were linearly related with shear rate. The decrease in blood viscosity might be attributed to changes in molecular weight, pH sensitivity and protein structure. The changes in rheological properties of irradiated rats' blood serum might be attributed to destruction changes in the haematological and dimensional properties of rats' blood products. PMID- 27005502 TI - Report: Bacterial susceptibility and resistance analysis of traumatic osteomyelitis. AB - With the rapid development of industry, agriculture and transportation, the high energy trauma happened accordingly, thus greatly increased the incidence of traumatic osteomyelitis. The clinical traumatic osteomyelitis was mainly the local bone tissue inflammation caused by bacteria infection as trauma or iatrogenic causes. The delaying recovery could cause bone defection or bone nonunion. The purpose of this paper was to contribute new reference for the clinical prevention and treatment through tremendous of disease-causing bacteria susceptibility and resistance analysis of osteomyelitis. PMID- 27005503 TI - Report: Prevention infection of newborn nosocomial and distribution of multiple drug resistant organism of the medicinal. AB - 2124 neonates were monitored from February 2013 to August 2014, among which 1119 were admitted from outpatient department (outpatient group), 782 were transferred from other departments (other department group), and 223 were from other hospitals (other hospital group). Through it we explore the distribution of multidrug resistant organism in neonates, which were admitted to the hospital through various ways, and therefore analyze the risk factors of nosocomial infection to avoid cross infection of multi drug resistant organism in neonatology department. The results showed that 105 strains of multi drug resistant bacteria were detected in the neonatal department. Among them, there were 57 strains from the outpatient group, 27 from the other department group, and 21 from the other hospital group. Neonates with the hospitalization time of more than 14 days and low birth weight infants (1500 g) were the high-risk groups of drug-resistant strains in nosocomial infection. So the infection in neonates from other departments or hospitals should be strengthen, especially the prevention and control in neonates with the hospitalization time than 14 days and low birth weight infants (1500 g) in order to reduce the occurrence of multiple drug-resistant strains cross infection. PMID- 27005504 TI - Identification of ofloxacin-resistant Mycobacterium tuberculosis by PCR-RFLP and Sequencing. AB - This study was planned to verify the resistance frequency of Ofloxacin (OFX) against Mycobacterium tuberculosis by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique and sequencing. Total 366 clinical samples of suspected TB patients were collected from various localities of central Punjab. All of them were found positive by ZN (Zeihl-Nelsen) staining method. Among them, 108 (29.5%) were found negative and 258 (70.5%) positive on PCR based study. The cases not responding to ATT were further characterized by proportion method and by PCR-RFLP to establish the drug resistance. Selected drug resistant case were further sequenced to confirm the results of amplified RFLP. The results showed that out of 118 drug resistant cases, 06 (5.08%), 03 (2.54%) were found resistant to OFX by drug susceptibility testing and PCR-RFLP respectively. The two strains were selected for sequencing procedure. The strain 79 showed point mutation at four points, at codon 70, 71, 76 and 78. The sequence of strain- 81 showed mutation at codon 95.PCR-RFLP is a useful molecular technique for the rapid detection of mutations and may be used to diagnose drug resistance but it should be confirmed by sequencing before starting 2(nd) and 3(rd) generation treatment because the restriction site is the cornerstone of PCR RFLP and mutation may be occurring elsewhere. PMID- 27005505 TI - Cloning and identification of the lobophorin biosynthetic gene cluster from marine Streptomyces olivaceus strain FXJ7.023. AB - A full length about 105 kb gene cluster containing 35 open reading frames involved in the biosynthesis of lobophorins was cloned and sequenced from a fosmid genomic library of Streptomyces olivaceus strain FXJ7.023. The cluster was identified by genome wide annotation and analysis of secondary metabolite biosynthesis gene clusters by anti SMASH and knockout of loading module-contained region of polyketide skeleton synthesis gene (the starter of lobS1). Gene cluster comparative analysis suggested that the cluster encoded the complete genes for lobophorin polyketide assembly, modification, substrate catalysis, regulation, transportation and resistance, and shows great identity to the newest reported lobophorin biosynthetic gene cluster from Streptomyces sp. SCSIO 01127, but with a significant gene rearrangement in the PKS modules. PMID- 27005506 TI - Protection of DNA during oxidative stress and cytotoxic potential of Artemisia absinthium. AB - Medicinal plants are rich in secondary metabolites (alkoloids, glycosides, coumarins, flavonides, steroids, etc.) and considered to be more effective and a safer alternative source to manage a variety of diseases related to liver, heart and kidney disordered. This study determines in vitro antioxidant and in vivo toxicological profile including hemolytic, brine shrimp lethality and mutagenicity of aerial parts of Artemisia absinthium. DNA protection assay was performed on pUC19 plasmid vector using H(2)O(2) as oxidative agent. Total phenolic and flavonoid content were determined using colorimetric methods. Toxicity of the plant was evaluated by brine shrimp lethality, hemolytic and mutagenic activity. DNA protection assay of the plant showed concentration dependent protective effect and at concentration 10MUL/mL revealed complete protective effect against H(2)O(2) induced DNA damage. Highest phenolic and flavonoid content was found to be 167.3 (mg GAE 100g DW(-1)) and 14 (mg CE 100g DW(-1)) respectively. Results showed that A. absinthium is potent against standard toxicological procedures, that indicates the presence of bioactive components in the plant and possess antioxidant activity that protects DNA against H(2)O(2) induced oxidative damage. Thus the results showed/support that A. absinthium provides significant health benefits. PMID- 27005507 TI - Comparative polyphenolic content and antioxidant activities of Genista tinctoria L. and Genistella sagittalis (L.) Gams (Fabaceae). AB - The aim of this study was focused on the polyphenolic composition and antioxidant capacity of Genista tinctoria L. and Genistella sagittalis (L.) Gams. A qualitative and quantitative characterization of the main phenolic compounds from the extracts were carried out using a HPLC-MS method. The total polyphenolic and flavonoid content was spectrophotometrically determined. The antioxidant activity towards various radicals generated in different systems was evaluated usingDPPH bleaching method, Trolox equivalent antioxidant capacity assay (TEAC) and Oxygen radical absorbance capacity (ORAC), and all indicated that G. tinctoria extract was more antioxidant than G. sagittalis extract.That was in good agreement with the total polyphenolic and flavonoidic content.Chlorogenic acid, p-coumaric acid, isoquercitrin and apigenin were identified in bothspecies. Caffeic acid, ferulic acid, hyperoside, rutin, quercitrin and luteolin were found only in G. tinctoria, while quercetin was determined in G. sagittalis. PMID- 27005508 TI - The correlation between the Glycated hemoglobin (HbA1c) in non-diabetics and cardiovascular risk factors. AB - This study aimed to discuss the relativity between the glycated hemoglobin (HbA1c) in non-diabetics and cardiovascular risk factors and definite the significance of predicting the cardiovascular risk factors through cross sectional research method. There were 2007 cases volunteers (including 650 cases of male, 1357 cases of female) from city community with complete information involved in the research of diabetes. The value of HbA1c 6.5% was set as the diagnose boundary of the diabetes. Differences were considered to be statistically significant at P<0.05. Hypertension, dyslipidemi, being overweight or obesity, age (male was over 45 years old and female was over 55 years old.), HbA1c 6.0% and fasting blood glucose (FBG) 6.1mmol/L were regarded as cardiovascular risk factors. Then we analyzed the number of risk factors for individuals in different HbA1c groups. Meanwhile, patients were grouped into zero, one, two, three, four or more groups with reference to the number of risk factors they had in order to compare the values of risk factors in different groups through Logistic regression. The results showed that (1) For those people who had no less than three risk factors, the frequency of risk factors was on the rise with the increase of HbA1c levels. (2) The value of HbA1c in different groups of risk factors rose with the increasing number of risk factors. There was a significant difference (P<0.001) between groups. (3) The Regression analysis showed that there was a stronger correlation between HbA1c levels and impaired glucose tolerance (IGT), fasting blood glucose (FBG) rather than age. So Non diabetics whose HbA1c levels ranged from 6.0% to 6.5% were at high risk of cardiovascular risk factors. HbA1c levels, which can be a prediction index for cardiovascular risk factors dependent from other cardiovascular risk factors for non-diabetics, and it were highly relevant with impaired glucose tolerance (IGT) and impaired fasting blood glucose (FBG). PMID- 27005509 TI - Discussion on robot-assisted laparoscopic cystectomy and Ileal neobladder surgery preoperative care. AB - To investigate the clinical applications of robot-assisted radical cystectomy with orthotopic ileal neobladder (RARC-INB) and make a preliminary summary. Retrospective analysis the clinical data of 12 patients underwent robotic bladder cancer (da vinci surgical system) assisted laparoscopic cystectomy with ileal orthotopic neobladder from March 2015 to April 2015. 12 cases were successful, with no surgical intervention, and organ damage occurred. The operation time was 330~470 min, which average (390.0+/-61.5) min; blood loss was 90~870 ml, which average (185.0+/-88.3) ml. One case of intraoperative blood transfusion was 400 ml. The enjoin eating time of postoperative intestinal ventilation was 3~6 d, and the average time was (4.0+/-1.5) d. Removal of ureteral stents time was 14~28 d and the average time was (21+/-7) d. Removal of the catheter time was 18~28 d and the average time was (23+/-5) d. Postoperative hospital stay 19~29 d and the average time was (24+/-5) dRARC-INB make the surgical tends to simplify, which was conducive to surgeon intraoperative control and assurance. RARC-INB make the surgical tends to use less trauma, less bleeding, complete lymphadenectomy, quick recovery, etc. It is a safe, effective and reliablethe method in the treatment of invasive bladder cancer. So the method should be widely applied. PMID- 27005510 TI - The study on clinical value of the detection about serum and Unconjugated Bilirubin in diagnosis of neonatal jaundice. AB - In this paper, the clinical value of the detection about serum and unconjugated bilirubin (UCB) in neonatal jaundice was studied to found an effective and rapid method for diagnose of neonatal jaundice. ALB (Serum Albumin), total serum bilirubin (TSB) and UCB were detected by ELISA method among the 100 cases with neonatal jaundice selected for the study. The values of ALB, UCB and TSB in moderate jaundice patients were (42.83+/-3.87) g/L, (287.35+/-44.38) MUm/L, (304.16+/-43.40) MUm/L, respectively; as for the severe jaundice patients, the values were (38.41+/-4.82) g/L, (354.38+/-48.75) MUm/L, (375.20+/-47.51) MUm/L. The results showed significant differences with the p< 0.05 between moderate and severe jaundice patients. The level of ALB, UCB, TSB in hemolytic jaundice, obstructive jaundice and jaundice caused by other infections also had significant differences, and the difference was statistically significant (p<0.05). The detection of ALB and UCB provides a useful method for the diagnosis and assessment of neonatal jaundice. PMID- 27005511 TI - Antioxidant and hepatoprotective activity of Hamelia patens extracts. AB - Hamelia patens is widely used in the traditional medicine of Mexico and Central America for the treatment of illnesses associated with inflammatory processes. In this study, antioxidant and hepatoprotective activity were assayed on the methanolic crude (ME), hexane (HE), ethyl acetate (AE), and butanol (BE) extracts of H. patens. The total phenolic content (TPC) as mg of gallic acid equivalents per g of dry extract was determined by Folin-Ciocalteu's method (ME=141.58+/ 11.99, HE=33.96+/-1.13, AE=375.18+/-13.09, BE=132.08+/-3.62), and antioxidant activity by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical-scavenging method (EC(50) ME=77.87+/-5.67, HE=236.64+/-26.32, AE=45.87+/-2.24, BE=50.97+/ 0.85MUg/mL). Hepatoprotective activity was evaluated through AST activity on HepG2 cells subjected to damage with CCl(4) (ME=62.5+/-3.41, HE=72.25+/-2.87, AE=63.50+/-4.20, BE=43.74+/-4.03). BE showed the greater hepatoprotective activity and a good antioxidant capacity, while HE did not show hepatoprotective or antioxidant activity. Cytotoxicity was evaluated on Vero cells cultures; none showed significant toxicity. PMID- 27005512 TI - Plasty of Human bites induced full thickness large area eyelid defects. AB - Large area eyelid defects induced by human biting was rare. A 43-year-old man was bited by a human. His Blepharocoloboma size was 60% percent of the upper eyelid, the horizontal defect length of defect area was 25mm, the vertical height was 5mm,a small mass like lateral eyelid tissue was left on the Lateralis lid margin. The toughness of this lateral eyelid tissue was enough to support the lateral canthus tissue transfered to the same area then the lateral eyelid tissue was sutured with the remaining sclera after which the sclera-conjunctiva was reconstructed. The skin tranfering from lateral canthus was sutured with conjunctiva without exposing. Eyelid defect was effectively repaired. The technique of lateralis cantholysis association with self remaining lateral eyelid tissue version was manifested an alternative and useful procedure for the reconstruction of large area upper full thickness eyelid defects. PMID- 27005513 TI - Pediatric hypervirulent Klebsiella pneumoniae septic arthritis. AB - Cases of infection with hypervirulent Klebsiella pneumoniae are gradually increasing in number, and cause life-threatening community-acquired infection even in immunocompetent patients. A 14-year-old boy developed septic hip arthritis due to hypervirulent K. pneumoniae (sequence type 23, serotype K1, magA positive). The patient initially seemed to have been successfully treated with antibiotics and surgical intervention, but septic arthritis developed into osteomyelitis of the femoral head and myositis, which required long-term antibiotic therapy and additional surgical intervention. This is the first pediatric case of hypervirulent K. pneumoniae septic hip arthritis. Treatment plans should mainly consist of antibiotic therapy and surgical intervention. Clinicians, even pediatricians, in developed countries should be aware of the increasing incidence of hypervirulent Klebsiella pneumoniae infection. PMID- 27005514 TI - Initiation and continuation of long-acting reversible contraception in the United States military healthcare system. AB - BACKGROUND: Long-acting reversible contraception is more effective for pregnancy prevention than shorter-acting contraceptive methods and has the potential to reduce healthcare disparities and costs. However, long-acting reversible contraception is underused in the United States. One population of interest is beneficiaries of the United States military healthcare system who have access to universal healthcare, including no-cost, no-copay contraception with unlimited method switching, and comprise a large, actual use cohort. Efforts to increase long-acting reversible contraception initiation and continuation in this population may improve health outcomes and mitigate the profound consequences of unintended or mistimed pregnancy on readiness and cost to the military. OBJECTIVE: We aimed to determine long-acting reversible contraception initiation and continuation rates among the diverse population with universal healthcare who are enrolled in the US military healthcare system. STUDY DESIGN: This study is a retrospective cohort of >1.7 million women, aged 14-40 years, who were enrolled in the US military healthcare system, TRICARE Prime, between October 2009 and September 2014. Individuals were assessed for long-acting reversible contraception initiation and continuation with the use of medical billing records. Method continuation and factors that were associated with early method discontinuation were evaluated with the Kaplan-Meier estimator and Cox proportional hazard models. RESULTS: During the study dates, 188,533 women initiated long-acting reversible contraception. Of these, 74.6% women selected intrauterine contraceptives. Method initiation rates remained relatively stable (41.7-50.1/1000 women/year) for intrauterine methods, although the rate for subdermal implants increased from 6.1-23.0/1000 women/year. In analysis of women who selected intrauterine contraceptives, 61.2% continued their method at 36 months, and 48.8% continued at 60 months. Among women who selected the implant, 32.0% continued their method at 36 months; however, 45.8% continued until 33 months (ie, 3 months before the currently recommended expiration date). Compared with intrauterine contraceptive users, implant users were more likely to discontinue their method during the 36 months after insertion (hazard ratio, 1.59; 95% confidence interval, 1.56-1.62; P < .001). Adolescents aged 14-19 years were the least likely age group to discontinue the implant before 36 months; women aged 35-40 years were the least likely to discontinue an intrauterine contraceptive before 60 months. In multivariable analysis that controlled for demographic factors and contraceptive type, early contraceptive method discontinuation was most likely among women aged 20-24 years, implant users, and women with method initiation in military clinics. CONCLUSION: In the US military healthcare system, TRICARE Prime, the initiation of long-acting reversible contraception is low but increasing, and continuation rates are high. This evidence supports long-acting reversible contraception as first-line recommendations for women of all ages who seek contraception. PMID- 27005515 TI - Impact of surgeon annual volume on short-term maternal outcome in cesarean delivery. AB - BACKGROUND: The annual procedure volume is an accepted marker for quality of care and has been documented in various medical fields. Surgeon volume has been shown to correlate with morbidity and mortality rates in surgical and high-risk medical procedures. Although cesarean delivery is 1 of the most common surgical procedures in the United States, the link between a surgeon's annual cesarean delivery volume and maternal outcome has never been tested. OBJECTIVE: The purpose of this study was to evaluate the impact of a surgeon's annual volume on short-term maternal outcome in cesarean deliveries. STUDY DESIGN: We performed a retrospective cohort study in a single tertiary center between 2006 and 2013. Cesarean deliveries were categorized into 2 groups based on the annual volume of cesarean delivery of the attending obstetrician. The "low" group included obstetricians with a low annual volume, whose annual volume of cesarean delivery was lower than median. The "high" group comprised obstetricians with a high annual volume whose annual volume was at median and above. Further analyses were done for quartiles and for 4 clinical relevant groups according to the annual number of cesarean deliveries that were performed/supervised by the attending obstetrician (<=20, 21-60, 61-120, and >120). The primary outcome was a composite adverse maternal outcome that included >=1 of the following outcomes: urinary or gastrointestinal tract injuries, hemoglobin drop >3 g/dL, blood transfusion, relaparotomy, puerperal fever, prolonged maternal hospitalization, and readmission. Secondary outcomes were operative times (skin incision to delivery and overall). RESULTS: A total of 11,954 cesarean deliveries were included; the median annual number of cesarean deliveries that were performed/supervised by 1 obstetrician was 48. Unadjusted analysis suggested that the patients in the high group had fewer urinary and gastrointestinal injuries (18/9278 [0.2%] vs 16/2676 [0.6%] injuries; P < .001), less blood loss as measured by hemoglobin drop >3 g/dL (1053/9278 [11.5%] vs 366/2676 [13.8%]; P < .001), and fewer cases of prolonged maternal hospitalization (80/9278 [0.9%] vs 39/2676 [1.5%]; P = .006). The rate of blood transfusion, relaparotomy, puerperal febrile morbidity, and readmission to hospital did not differ between groups. Multivariable regression analysis showed that cesarean delivery performed/supervised by the high group resulted in a significantly lower composite adverse maternal outcome (15.8% vs 18.9%; odds ratio, 0.86; 95% confidence interval, 0.78-0.95; P = .004). This was related primarily to a decreased frequency of urinary and gastrointestinal injuries, lower likelihood of hemoglobin drop >3 g/dL, and lower incidence of prolonged maternal hospitalization. Operative times were significantly shorter for the high group. Composite adverse maternal outcome ranged from 21.8% in the lowest quartile to 17.9% in quartile 2, to 17.4% in quartile 3, and 15.6% in quartile 4. quartile 4 served as the reference; quartile 3 had an odds ratio of 1.14 (95% confidence interval, 1.01-1.29; P = .029); quartile 2 had an odds ratio of 1.18 (95% confidence interval, 1.02-1.36; P = .021, and quartile 1 had an odds ratio of 1.51 (95% confidence interval, 1.14-1.99; P = .004) for composite adverse maternal outcome. Composite adverse maternal outcome ranged from 21.5% in clinical group 1 to 17.5% in clinical group 2, to 17.9% in clinical group 3, and 15.2% in clinical group 4 (P = .001). Cesarean delivery performed/supervised by clinical groups 2, 3, and 4 in comparison with clinical group 1 were associated with a statistically significant risk reduction, (23%, 25%, and 34% respectively). CONCLUSION: Maternal composite morbidity is decreased as the volume of cesarean deliveries that are performed or supervised by obstetricians increases. PMID- 27005517 TI - A cautionary fail. PMID- 27005518 TI - Intermolecular dearomative C2-arylation of N-Ac indoles activated by FeCl3. AB - We report the FeCl3-mediated direct addition of electron-rich arenes to the C2 position of electrophilic N-Ac indoles under mild conditions (room temperature, air). No functional group is required on the arene nucleophile: one of its C-H bonds is added to the C2[double bond, length as m-dash]C3 double bond of the indole nucleus in a Friedel-Crafts-type reaction. This dearomatisation process delivered a broad range of C2-arylated indolines. PMID- 27005516 TI - Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury. AB - Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM derived cells infiltrate into the spinal cord and differentiate into microglia like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID- 27005519 TI - Extrapolating Survival from Randomized Trials Using External Data: A Review of Methods. AB - This article describes methods used to estimate parameters governing long-term survival, or times to other events, for health economic models. Specifically, the focus is on methods that combine shorter-term individual-level survival data from randomized trials with longer-term external data, thus using the longer-term data to aid extrapolation of the short-term data. This requires assumptions about how trends in survival for each treatment arm will continue after the follow-up period of the trial. Furthermore, using external data requires assumptions about how survival differs between the populations represented by the trial and external data. Study reports from a national health technology assessment program in the United Kingdom were searched, and the findings were combined with "pearl growing" searches of the academic literature. We categorized the methods that have been used according to the assumptions they made about how the hazards of death vary between the external and internal data and through time, and we discuss the appropriateness of the assumptions in different circumstances. Modeling choices, parameter estimation, and characterization of uncertainty are discussed, and some suggestions for future research priorities in this area are given. PMID- 27005520 TI - Using CART to Identify Thresholds and Hierarchies in the Determinants of Funding Decisions. AB - There is much interest in understanding decision-making processes that determine funding outcomes for health interventions. We use classification and regression trees (CART) to identify cost-effectiveness thresholds and hierarchies in the determinants of funding decisions. The hierarchical structure of CART is suited to analyzing complex conditional and nonlinear relationships. Our analysis uncovered hierarchies where interventions were grouped according to their type and objective. Cost-effectiveness thresholds varied markedly depending on which group the intervention belonged to: lifestyle-type interventions with a prevention objective had an incremental cost-effectiveness threshold of $2356, suggesting that such interventions need to be close to cost saving or dominant to be funded. For lifestyle-type interventions with a treatment objective, the threshold was much higher at $37,024. Lower down the tree, intervention attributes such as the level of patient contribution and the eligibility for government reimbursement influenced the likelihood of funding within groups of similar interventions. Comparison between our CART models and previously published results demonstrated concurrence with standard regression techniques while providing additional insights regarding the role of the funding environment and the structure of decision-maker preferences. PMID- 27005521 TI - Cost Recommendation under Uncertainty in IQWiG's Efficiency Frontier Framework. AB - BACKGROUND: The National Institute for Quality and Efficiency in Health Care (IQWiG) employs an efficiency frontier (EF) framework to facilitate setting maximum reimbursable prices for new interventions. Probabilistic sensitivity analysis (PSA) is used when yes/no reimbursement decisions are sought based on a fixed threshold. In the IQWiG framework, an additional layer of complexity arises as the EF itself may vary its shape in each PSA iteration, and thus the willingness-to-pay, indicated by the EF segments, may vary. OBJECTIVES: To explore the practical problems arising when, within the EF approach, maximum reimbursable prices for new interventions are sought through PSA. METHODS: When the EF is varied in a PSA, cost recommendations for new interventions may be determined by the mean or the median of the distances between each intervention's point estimate and each EF. Implications of using these metrics were explored in a simulation study based on the model used by IQWiG to assess the cost effectiveness of 4 antidepressants. RESULTS: Depending on the metric used, cost recommendations can be contradictory. Recommendations based on the mean can also be inconsistent. Results (median) suggested that costs of duloxetine, venlafaxine, mirtazapine, and bupropion should be decreased by ?131, ?29, ?12, and ?99, respectively. These recommendations were implemented and the analysis repeated. New results suggested keeping the costs as they were. The percentage of acceptable PSA outcomes increased 41% on average, and the uncertainty associated to the net health benefit was significantly reduced. CONCLUSIONS: The median of the distances between every intervention outcome and every EF is a good proxy for the cost recommendation that would be given should the EF be fixed. Adjusting costs according to the median increased the probability of acceptance and reduced the uncertainty around the net health benefit distribution, resulting in a reduced uncertainty for decision makers. PMID- 27005523 TI - Extending the biosynthetic repertoires of cyanobacteria and chloroplasts. AB - Chloroplasts in plants and algae and photosynthetic microorganisms such as cyanobacteria are emerging hosts for sustainable production of valuable biochemicals, using only inorganic nutrients, water, CO2 and light as inputs. In the past decade, many bioengineering efforts have focused on metabolic engineering and synthetic biology in the chloroplast or in cyanobacteria for the production of fuels, chemicals and complex, high-value bioactive molecules. Biosynthesis of all these compounds can be performed in photosynthetic organelles/organisms by heterologous expression of the appropriate pathways, but this requires optimization of carbon flux and reducing power, and a thorough understanding of regulatory pathways. Secretion or storage of the compounds produced can be exploited for the isolation or confinement of the desired compounds. In this review, we explore the use of chloroplasts and cyanobacteria as biosynthetic compartments and hosts, and we estimate the levels of production to be expected from photosynthetic hosts in light of the fraction of electrons and carbon that can potentially be diverted from photosynthesis. The supply of reducing power, in the form of electrons derived from the photosynthetic light reactions, appears to be non-limiting, but redirection of the fixed carbon via precursor molecules presents a challenge. We also discuss the available synthetic biology tools and the need to expand the molecular toolbox to facilitate cellular reprogramming for increased production yields in both cyanobacteria and chloroplasts. PMID- 27005522 TI - TFIIS.h, a new target of p53, regulates transcription efficiency of pro-apoptotic bax gene. AB - Tumor suppressor p53 transcriptionally regulates hundreds of genes involved in various cellular functions. However, the detailed mechanisms underlying the selection of p53 targets in response to different stresses are still elusive. Here, we identify TFIIS.h, a transcription elongation factor, as a new transcriptional target of p53, and also show that it can enhance the efficiency of transcription elongation of apoptosis-associated bax gene, but not cell cycle associated p21 (CDKN1A) gene. TFIIS.h is revealed as a p53 target through microarray analysis of RNAs extracted from cells treated with or without inauhzin (INZ), a p53 activator, and further confirmed by RT-q-PCR, western blot, luciferase reporter, and ChIP assays. Interestingly, knocking down TFIIS.h impairs, but overexpressing TFIIS.h promotes, induction of bax, but not other p53 targets including p21, by p53 activation. In addition, overexpression of TFIIS.h induces cell death in a bax- dependent fashion. These findings reveal a mechanism by which p53 utilizes TFIIS.h to selectively promote the transcriptional elongation of the bax gene, upsurging cell death in response to severe DNA damage. PMID- 27005524 TI - [Application of cohort study in cancer prevention and control]. AB - Cancer control is a long-term work. Cancer research and intervention really need the support of cohort study. In the recent years, more and more cohort studies on cancer control were conducted in China along with the increased ability of scientific research in China. Since 2010, Cancer Hospital, Chinese Academy of Medical Sciences, collaborated with Lanzhou University and the Worker' s Hospital of Jinchuan Group Company Limited, have carried out a large-scale cohort study on cancer, which covered a population of more than 50 000 called " Jinchang cohort". Since 2012, a National Key Public Health Project, "cancer screening in urban China" , has been conducted in Jinchang, which strengthened the Jinchang cohort study. Based on the Jinchang cohort study, historical cohort study, cross sectional study and prospective cohort study have been conducted, which would provide a lot of evidence for the cancer control in China. PMID- 27005525 TI - [Cancer burden in the Jinchang cohort]. AB - OBJECTIVE: To understand the disease burden caused by cancers in Jinchang cohort, and develop effective strategies for cancer prevention and control in this population. METHODS: The cancer mortality data from 2001 to 2013 and the medical records for cancer patients from 2001 to 2010 in Jinchang cohort were collected. The disease burden caused by cancer was analyzed by using mortality rate, potential years of life lost (PYLL), working PYLL (WPYLL), and direct economic burden. RESULTS: During 2001-2013, in Jinchang cohort, the five leading cancers ranked by mortality rate were lung cancer (78.06/100,000), gastric cancer (38.03/100,000), liver cancer (37.23/100,000), esophageal cancer (19.06/100,000), and colorectal cancer (9.53/100,000). The five leading cancers in terms of PYLL (person-years) and WPYLL (person-years) were lung cancer (3480.33, 1161.00), liver cancer (2809.03, 1475.00), gastric cancer (2120.54, 844.00), esophageal cancer (949.61, 315.00), and colorectal cancer (539.90, 246.00). From 2001 to 2010, the five leading cancers in term of average daily cost of hospitalization were gastric cancer (8,102.23 Yuan), esophageal cancer (7135.79 Yuan), colorectal cancer (7064.38 Yuan), breast cancer (6723.53 Yuan), and lung cancer (6309.39 Yuan). CONCLUSIONS: The cancers common causing higher disease burden in Jinchang cohort were lung cancer, gastric cancer, liver cancer, esophageal cancer and colorectal cancer. The lung cancer disease burden was the highest. PMID- 27005526 TI - [Disease burden of lung cancer in Jinchang cohort]. AB - OBJECTIVE: To understand the current status of lung cancer disease burden in Jinchang cohort. METHODS: In this historical cohort study, the mortality data of the lung cancer from 2001 to 2013 and medical records of the lung cancer cases from 2001 to 2010 in Jinchang cohort were used, analyze mortality, direct economic burden, potential years of life lost (PYLL) and working PYLL (WPYLL) associated with lung cancer. RESULTS: A total of 434 lung cancer deaths occurred in Jinchang cohort from 2001 to 2013. The crude mortality rate of lung cancer was 78.06 per 100,000 from 2001 to 2013, with the increasing rate of 4.77%. The mortality rate of lung cancer in males and females were about 108.90 per 100,000 and 26.08 per 100,000 with the increasing rate of 4.24% and 6.91%, respectively. During the thirteen years, the PYLL and average PYLL (APYLL) of lung cancer were 3 721.71 person-years and 8.58 years. The APYLL of lung cancer in females (15.94 years) was higher than that in males (7.87 years). The WPYLL and the average WPYLL (AWPYLL) of lung cancer were 1161.00 person-years and 2.68 years, respectively. The AWPYLL of lung cancer was also higher in females than in males. The direct economic burden of lung cancer from 2001 to 2010 in Jinchang cohort was 6309.39 Yuan per case with no increased trend. CONCLUSION: Lung cancer is the main health problem in Jinchang cohort, causing heavy disease burden. PMID- 27005527 TI - [Disease burden of gastric cancer in Jinchang cohort]. AB - OBJECTIVE: To understand the current status of disease burden caused by gastric cancer in Jinchang cohort. METHODS: In this historical cohort study, the data of gastric cancer deaths from 2001 to 2013 and the medical records of gastric cancer cases from 2001 to 2010 in Jinchang cohort were collected to analyze the mortality, potential years of life lost (PYLL), working PYLL (WPYLL) associated with gastric cancer, and the medical expenditure data were used to evaluate the direct economic burden. Spearman correlation analysis and the average growth rate were used to describe the change trend of disease burden of gastric cancer. RESULTS: A total of 213 gastric cancer deaths occurred in Jinchang cohort from 2001 to 2013. The average annual crude mortality rate of gastric cancer was 38.30 per 100,000 in Jinchang cohort during 2001-2013 and no obvious change was observed. The crude mortality rate in males was 6.84 times higher than that in females. Gastric cancer death mainly occurred in age group 50-79 years (82.62%), while the mortality rates was increasing among the people under 50 years with an average annual increase rate of 0.77%. The annual average PYLL (APYLL) and average WPYLL (AWPYLL) caused by gastric cancer decreased by 8.43% and 10.46%, respectively. No obvious change in medical expenditure of gastric cancer cases was observed in Jinchang Cohort during 2001-2010, and the medical expenditure and average daily cost of hospitalization were 8102.23 Yuan, and 463.45 Yuan per capita, respectively. CONCLUSIONS: The burden of disease for gastric cancer was heavy in Jinchang cohort. The PYLL and WPYLL had no change, while the APYLL and AWPYLL showed a increasing trend during the last ten years. Direct economic burden of inpatients with gastric cancer had no change. PMID- 27005528 TI - [Disease burden of liver cancer in Jinchang cohort]. AB - OBJECTIVE: To understand the current status of the disease burden of liver cancer in Jinchang cohort. METHODS: All the liver cancer death data from 2001 to 2013 and medical records of liver cancer cases from 2001 to 2010 in Jinchang cohort were collected for the analyses of the mortality, standardized mortality, potential years of life lost (PYLL) and working PYLL (WPYLL) associated with liver cancer. Spearman correlation and the average growth rate were used to analyze the trends. RESULTS: A total of 207 liver cancer deaths occurred in Jinchang cohort from 2001 to 2013, accounting for 16.68% of total cancer deaths. There were 259 liver cancer inpatients, accounting for 6.79% of the total cancer cases inpatients, in which 83 died (32.05%). Liver cancer death mainly occurred in males, accounting for 88.89%, and the liver cancer deaths in females accounted for 11.11%. The standardized mortality rate was 42.32/100,000 in males and 15.31/100,000 in females. The growth rate of liver cancer mortality was 5.62% from 2001 to 2013. Liver cancer deaths mainly occurred in age groups 60-69 years (26.57%) and 50-59 years (24.15%). The PYLL was 2906.76 person-years, the average PYLL was 14.04 years. The WPYLL was 1477.00 person-years and the average WPYLL was 7.14 years. The direct economic burden of liver cancer was 6270.78 Yuan per person, 301.75 Yuan per day. The average stay of hospitalization was 21.32 days. CONCLUSION: The mortality rate of liver cancer is increasing and the disease burden is still heavy. PMID- 27005529 TI - [Disease burden of colorectal cancer in Jinchang cohort]. AB - OBJECTIVE: To evaluate the disease burden of colorectal cancer in Jinchang cohort, and provide evidence for preventing colorectal cancer and reducing the disease burden of colorectal cancer in the cohort. METHODS: The colorectal cancer mortality data from 2001 to 2013 and the medical records of colorectal cancer patients from 2001 to 2010 were collected for this retrospective cohort study. The colorectal cancer disease burden was described by using mortality rate, standardized mortality rate, medical expenditure, potential years of life lost (PYLL), average potential years of life lost (APYLL), working potential years of life lost (WPYLL), and average working potential years of life lost (AWPYLL). The development trend in disease burden of colorectal cancer was analyzed by using Spearman correlation and the average growth rate. RESULTS: The crude mortality rate of colorectal cancer from 2001 to 2013 was 9.53/100,000 with the average annual growth rate of 12.89%. The PYLL, APYLL, WPYLL and AWPYLL of colorectal cancer were 485.00 person-years, 9.15 years, 253.00 person-years, and 4.77 years, respectively. The direct medical expenditure due to colorectal cancer was 7064.38 Yuan per case and 408.43 Yuan per day. There was no increasing trend in the direct medical expenditure due to colorectal cancer. CONCLUSION: Colorectal cancer mortolity rate was on the rise and it caused heavy disease burden in Jinchang cohort. PMID- 27005530 TI - [Epidemiological characteristics of Zika virus disease]. AB - Zika virus disease is an emerging mosquito-borne acute infectious disease caused by Zika virus, so far there have been no available vaccine or specific treatment. Currently, the outbreaks of Zika virus disease mainly occurs in the Americas, but the regional distribution of the disease is in rapid expansion, 34 countries and territories have reported autochthonous transmission of the virus. The illness is usually mild with very rarely death, but increased reports of birth defects and neurologic disorders in the areas affected by Zika virus has caused extensive concern worldwide. In China, the competent vectors for Zika virus are widely distributed, imported viraemic cases may become a source of local transmission of the virus. However, Zika virus disease is preventable, the spread of virus could be stopped when the effective prevention measures are taken. This paper summarizes the retrieval results from Medline database and the information from the reports of the governments of countries affected or health organizations about the epidemiological characteristics of Zika virus disease. PMID- 27005531 TI - [Role of novel risk factors in predicting risk of ischemic cardiovascular diseases in middle aged men in twenty years in Shanghai]. AB - OBJECTIVE: To examine the existing Framingham Risk Score (FRS) and Chinese Risk Score (CRS) in predicting the development of ischemic cardiovascular diseases (ICVD), and determine potential added value of novel risk factors. METHODS: The China Multi-Provincial Cohort Study (CMCS) was a population-based prospective cohort study in 11 provinces of China. An annual follow up was conducted in 840 men aged 35 to 64 years in Shanghai cohort, who were without coronary heart disease and stroke at baseline examination in 1992, to collect the incidence data of ICVD events (coronary death, myocardial infarction, and ischemic stroke). The detection of novel risk factors were conducted for the cohort in 2007. The basic Framingham and Chinese prediction scores power were assessed by using C-statistic of ICVD events associated with risk scores, then the novel risk factors were evaluated by adding them independently to the basic Chinese models. The area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement(IDI) were calculated to determine if each of the novel risk factors improved risk prediction. RESULTS: By the end of December 2014, 24 cases of coronary heart disease (myocardial infarction or/and coronary death), 45 cases of ischemic stroke had occurred in 840 subjects in Shanghai cohort with a follow-up of 22.3 years averagely. Both the FRS and CRS had predicting power for ICVD, the AUCs were 0.6576 (95%CI: 0.5942-0.7240) and 0.7265 (95%CI: 0.6643 0.7887), respectively. The incremental AUC was 0.0689 (95%CI: 0.0196-0.1171) (P=0.006). None of the novel risk factors significantly improved the AUC. High sensitive-CRP (hs-CRP) was the only novel risk factor resulting in a significant increase of NRI. CRS in 2007 significantly improved the IDI, but net changes were small. CONCLUSIONS: CRS had high power in the 20-year risk prediction for ICVD in middle-aged men in Shanghai. The inclusion of hs-CRP could make some improvement in risk prediction, but is unlikely to be meaningful when reclassification or new discrimination strategy are made which can change the clinical risk. PMID- 27005532 TI - [Relationship between body weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus]. AB - OBJECTIVE: To explore the relationship between weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus (T2DM). METHODS: The data of 14 population samples from China Multicenter Collaborative Study of Cardiovascular Epidemiology conducted in 1998 were used. Approximately 1 000 men and women in each sample were surveyed for cardiovascular disease risk factors, including body weight at age 25 years. The body mass index (BMI) at the age 25 years was calculated. The association between body weight in early adulthood and body weight change at middle age and T2DM was examined by using logistic regression model. RESULTS: The incidence of T2DM in low weight group (BMI<18.5 kg/m(2)), normal weight group (BMI: 18.5-23.9 kg/m(2)), overweight group (BMI: 24.0-27.9 kg/m(2)) and obese group (BMI:>=28.0 kg/m(2)) at 25 years old were 2.4%(30/1263), 2.8%(266/9562), 4.0%(70/1739) and 6.4% (7/110), respectively (P value for trend<0.01). The incidence of T2DM for adults with weight change <-7.5 kg, -7.5--2.6 kg, -2.5-2.5 kg, 2.6-7.5 kg, 7.6-12.5 kg and >12.5 kg at middle age were 2.5% (18/712), 1.3%(21/1629), 2.1%(48/2330), 2.3%(59/2585), 3.7%(94/2518), and 4.6% (133/2900) respectively. (P value for trend <0.01), Multivariate logistic regression analysis showed that overweight and obesity at age 25 years and subsequent weight gain were positively correlated with T2DM after adjusted other risk factors (all P values for trend <0.01). CONCLUSION: Overweight and obesity in early adulthood and weight gain at middle age were both independently associated with the increased risk of T2DM in middle aged men and women. PMID- 27005533 TI - [Analysis on reliability and validity of SF-36 scale in urban residents]. AB - OBJECTIVE: To evaluate the reliability and validity of SF-36 scale in urban residents, and provide reference for the selection of suitable health measure tools for urban residents. METHODS: Multi-stage cluster stratified sampling was conducted to select the residents aged >=18 years in three urbanized communities of Hangzhou. SF-36 scale was used for the measurement of the quality of life and Spearman-Brown and Cronbach' s alpha coefficients were used for the evaluation of split-half reliability and internal consistency reliability. The convergent and discriminative validity were evaluated by using the success rate of experiments and the criterion-related validity was evaluated with correlation analysis and non-parameter test. Structural equation modeling was used in the evaluation of contract validity. RESULTS: SF-36 scale had good split-half reliability (R=0.94) and internal-consistency reliability (except for bodily pain and vitality, Cronbach's alpha range: 0.70-0.91). The convergent validity (88.57%), discriminate validity (successful rates 90.61%) and the criterion-related validity (gammas=0.56, the score was consistent with the self-reported health status) were good. Second-order confirmatory factor analysis model was not well fitted (GFI= 0.721, AGFI= 0.682, CFI= 0.731, RMR= 0.084, RMSEA= 0.098), indicating that the construct validity was poor. CONCLUSION: The reliability, consolidation validity, discrimination validity and criterion-related validity of SF-36 scale were good, while the construct validity was poor. Improvement is needed when the scale is used for urban residents. PMID- 27005534 TI - [Associations between dormitory environment/other factors and sleep quality of medical students]. AB - OBJECTIVE: To investigate the sleep quality and related factors among medical students in China, understand the association between dormitory environment and sleep quality, and provide evidence and recommendations for sleep hygiene intervention. METHODS: A total of 555 undergraduate students were selected from a medical school of an university in Beijing through stratified-cluster random sampling to conduct a questionnaire survey by using Chinese version of Pittsburgh Sleep Quality Index (PSQI) and self-designed questionnaire. Analyses were performed by using multiple logistic regression model as well as multilevel linear regression model. RESULTS: The prevalence of sleep disorder was 29.1%(149/512), and 39.1%(200/512) of the students reported that the sleep quality was influenced by dormitory environment. PSQI score was negatively correlated with self-reported rating of dormitory environment (gammas=-0.310, P<0.001). Logistic regression analysis showed the related factors of sleep disorder included grade, sleep regularity, self-rated health status, pressures of school work and employment, as well as dormitory environment. RESULTS of multilevel regression analysis also indicated that perception on dormitory environment (individual level) was associated with sleep quality with the dormitory level random effects under control (b=-0.619, P<0.001). CONCLUSIONS: The prevalence of sleep disorder was high in medical students, which was associated with multiple factors. Dormitory environment should be taken into consideration when the interventions are taken to improve the sleep quality of students. PMID- 27005535 TI - [Effect of supply of fresh poultry products on reducing environment contamination of avian influenza virus in markets]. AB - OBJECTIVE: To evaluate the effect of supply of fresh poultry products on reducing environment contamination of avian influenza virus (AIV) in markets in Guangzhou. METHODS: A total of 40 markets, including 20 selling alive poultry and 20 selling fresh poultry products, were selected randomly in Guangzhou to conduct environment surveillance in 80 poultry stalls every 4 months from July 2014 to April 2015. Four smear samples were collected from different sites of each poultry stall to detect nucleic acid of AIV. The positive samples were further detected for AIV subtype H5, H7 and H9 nucleic acids. RESULTS: Among 40 alive poultry stalls, 95.0% (38/40) kept alive poultry overnight, 25.0% (10/40) were disinfected daily, 95.0% (38/40) were cleaned up weekly, 95.0% (38/40) were closed for one day every month. Among 40 fresh poultry product stalls, 20.0% (8/40) were disinfected daily, 90.0% (36/40) were cleaned up weekly, and 96.0% (38/40) ever sold dressed poultry from alive poultry markets. The positive rate of AIV in alive poultry markets was 40.4% (252/623), higher than that in fresh poultry product markets (32.3%, 197/610), the difference was significant (chi(2)=8.85, P=0.003), and the positive rate of subtype H9 virus in alive poultry markets was 28.6% (178/623), higher than that in fresh poultry product markets (16.2%, 99/610), the difference was significant (chi(2)=26.95, P<0.001). In fresh poultry product markets, the positive rate of AIV in stalls selling dressed poultry was 37.3% (180/482), higher than that in stalls selling no dressed poultry (13.3%, 17/128), the difference was significant (chi(2)=26.78, P<0.001), and the positive rate of subtype H9 virus in stalls selling dressed poultry was 19.1% (92/482), higher than that in stalls selling no dressed poultry (5.5%, 7/128), the difference was significant (chi(2)=13.80, P<0.001). Both the positive rate of AIV and the positive rate of subtype H9 virus were highest in the second round surveillance (October 2014). The differences in AIV and its subtype H5, H7 and H9 virus positive rates of environmental samples from four different sites were not significant, respectively. In the same sample site, the positive rate of subtype H9 virus in alive poultry markets was higher than that in fresh poultry product markets the difference was significant (P<0.05). CONCLUSIONS: The supply of fresh poultry products could effectively reduce the level of environment contamination of AIV in markets. Dressed poultry supplement caused the risk of AIV spread in fresh poultry product markets. PMID- 27005536 TI - [HIV detection and prevalence among sexullay transmitted diseases clinic patients in seven provinces (Autonomous Region)]. AB - OBJECTIVE: To understand the performance of HIV detection, prevalence and related factors in sexually transmitted diseases (STD) clinics and provide evidence for the improvement of HIV test and counsel services. METHODS: From January 2013 to December 2014, a survey was conducted in 9 sentinel STD clinics in Laoning province and other 6 provinces. Newly diagnosed STD patients were asked to fill out in STD reporting cards and encouraged to receive HIV test and counsel. Univariate and multivariate logistic regression analyses were conducted to identify the factors associated with the acceptance of HIV test. RESULTS: Of the 5063 STD cases reported, 2668(52.7%) received the HIV screening test, in which, 63(2.4%) were positive for HIV. Multivariate logistic regression analysis indicated that the acceptance of HIV test was associated with the location of STD clinic, patients' original living place, patient' s marital status, type of STD, and reasons for seeking medical care in STD clinic. CONCLUSION: HIV counsel and test were well accepted by STD patients, and the HIV positive rate was high. More studies are needed to further explore factors that impede the acceptance of HIV counsel and test services in STD clinics. PMID- 27005537 TI - [HIV infection incidence among men who have sex with men in common bathing pool in Tianjin: a cohort study]. AB - OBJECTIVE: To investigate incidence of HIV infection and identify associated risk factors among men who have sex with men (MSM) in common bathing pools in Tianjin. METHODS: A prospective cohort study was conducted among the MSM recruited in a common bathing pool in Tianjin from 2011 to 2013. A total of 733 MSM were surveyed to obtain the information about their sociodemographic characteristics, HIV-related knowledge awareness and sexual behaviors, and subsequent follow-up surveys were carried out every four months. Cox regression analysis was conducted to identify the risk factors for HIV infection. RESULTS: A total of 59 HIV infection cases were found in the 2.5-years follow-up survey. The cumulative follow-up time was 7384.9 person-months. The incidence rate of HIV infection was 9.59/100 person-year. The multivariate Cox regression analysis showed that young age, low score of HIV/AIDS knowledge awareness (HR=1.82, 95%CI:1.03-2.66), having two and more sexual partners during past 6 months (HR=1.74, 95%CI: 1.26-2.58) and syphilis (HR=2.36, 95%CI:1.31-3.27) were significantly associated with HIV infection in this MSM cohort. CONCLUSIONS: Low score of HIV/AIDS knowledge awareness, young age, having two and more sexual partners during past 6 months and syphilis were the risk factors for HIV infection in MSM in common bathing pools. It is necessary to strengthen the HIV surveillance and intervention in this population. PMID- 27005538 TI - [Factors associated with high-risk behaviors among people newly diagnosed to be infected with HIV through heterosexual contact before and after diagnosis in some areas in Henan province]. AB - OBJECTIVE: To understand the factors associated with high risk behaviors among people newly diagnosed to be infected with HIV through heterosexual contact before and after diagnoses in some areas in Henan province, and evaluate the risk of secondary transmission. METHODS: A face to face interview was conducted among people infected with HIV through heterosexual contact by using self-designed questionnaires during January-May in 2015. RESULTS: Among 361 HIV infected persons, the proportions of those with commercial heterosexual behaviors or sex with irregular sex partners decreased from 77.3%(279/361) and 28.5%(103/361) before diagnosis to 13.6%(49/361) and 2.5%(9/361) after diagnosis, the difference was significant (chi(2)=16.66, P<0.001; chi(2)=4.80, P=0.03). The subjects surveyed always had more commercial heterosexual behaviors in Henan, Guangdong and Zhejiang provinces before and after diagnosis. After HIV infection confirmation, the condom use rates were 51.0%(25/49) for commercial heterosexual behaviors, 88.5% (184/208) for sex with regular partners and 88.9%(8/9) for sex with irregular partners, respectively. Multivariate logistic regression analysis indicated that risk behaviors associated with HIV transmission included commercial sexual behaviors, previous HIV detection and age of 35 years or older. CONCLUSIONS: Extramarital heterosexual behavior has posed serious challenge to the prevention and control of HIV spread. It is necessary to inform the HIV test results, improve the intervention and promote condom use in people with history of commercial sex and people aged >=35 years. PMID- 27005539 TI - [Prevalence of high risk behaviors in HIV infected persons aged >=50 years in selected counties of Yunnan province]. AB - OBJECTIVE: To understand the prevalence of high risk behaviors and influencing factors among HIV infected persons aged >=50 years. METHODS: Face to face questionnaire interview was conducted among the HIV infected persons selected in Jianshui, Gejiu and Mengzi counties in Yunnan province through random sampling in June 2015. The sample size was 450. RESULTS: Among the HIV infected persons surveyed, 41.2% (122/296) had sexual behaviors with their spouses during past year, and the consistent condom use rate was 66.4% (81/122). Among the HIV infected males, 8.9% (28/313) had commercial sexual behaviors during past year, and the consistent condom use rate was 17.9% (5/28). Among the HIV infected females, 0.7% were still engaged in commercial sex service during past year. Among the 450 HIV infected persons, 32 (7.1%) reported having casual sex behaviors during past years, and the consistent condom use rate was 18.7% (6/32). The rate of commercial sexual behavior in urban residents (13.4%, 19/115) was higher than that in rural residents (4.5%, 9/198), the difference was statistically significant (chi(2)=11.715, P=0.001). The risk factors for commercial sex behaviors included lack of family and social support, aged 50-59 years, living in urban area, higher income and being male. The risk factors for using no condom included living in rural area, lower education level, lack of family and social support and higher income. CONCLUSIONS: Risk sex behaviors are still prevalent in HIV infected people aged >50 years, which exacerbated HIV transmission. Further efforts should be focused on the education about AIDS prevention and control and promoting protected sexual behaviors. Additional effort should be done to improve the family and social support for HIV infected people aged >50 years. Moreover, comprehensive intervention for low-paid female sex workers also needs to be strengthened. PMID- 27005540 TI - [Influence of daily ambient temperature on mortality and years of life lost in Chongqing]. AB - OBJECTIVE: To evaluate the influence of extreme ambient temperature on mortality and years of life lost (YLL) in Chongqing. METHODS: The daily mortality, meteorology and air pollution index data in Chongqing from the 1(st) January 2010 to the 31(st) December 2013 were collected. Distributed lag non-linear model (DLNM) was used to assess the influence of daily ambient temperature on daily number of deaths and daily YLL respectively. The delayed and cumulative effects of extreme temperature on sex, age, and cause-specific mortality were also assessed. RESULTS: The relationships between ambient temperature and non accidental, cardiovascular disease and respiratory disease mortalities and YLL were U-shaped or W-shaped. The effect of heat was obvious on that day, peaked on day 7, and lasted for two weeks, whereas the effect of cold was obvious a week later and lasted for a month. As 1 C increase of ambient temperature, the cumulative relative risks (CRR) of high temperature across lag 0-7 days on non accidental, respiratory disease and cardiovascular disease mortalities were 1.05 (95%CI: 1.03-1.07), 1.08 (95%CI: 1.05-1.11) and 1.05 (95%CI: 1.01-1.09) respectively. The effects of heat on YLL for each cause were 23.81 (95%CI: 12.31 35.31), 14.34 (95%CI: 8.98-19.70) and 4.43 (95%CI: 1.64-7.21), respectively. On cold days, 1 C decrease of ambient temperature was correlated with an increase in CRR of 1.06 (95%CI: 1.04-1.08), 1.09 (95%CI:1.06-1.12) and 1.06 (95%CI: 1.02 1.11) from lag 0 to 14 for non-accidental, respiratory disease and cardiovascular disease mortalities, respectively. The estimated YLL were 23.34 (95%CI: 10.04 36.64), 16.39 (95%CI: 10.19-22.59) and 2.61 (95%CI: -0.61-5.82). People aged >=65 years tend to have higher CRR and YLL than those aged <65 years. On high temperature days, the CRR in women was higher than that in men, while the YLL in women was lower than that in men. On low temperature days, both the CRR and YLL in women were higher than those in men. CONCLUSIONS: Both high and low ambient temperature have adverse health effects. People aged >=65 years are more sensitive to both high and low ambient temperature. Younger men are more sensitive to high ambient temperature and women and elder men are sensitive to low ambient temperature. It is necessary to take targeted measures to protect the population in Chongqing from the adverse influence of extreme ambient temperature. PMID- 27005541 TI - [Study on smoking-attributed mortality by using all causes of death surveillance system in Tianjin]. AB - OBJECTIVE: To understand the smoking-attributed mortality by inclusion of smoking information into all causes of death surveillance. METHODS: Since 2010, the information about smoking status, smoking history and the number of cigarettes smoked daily had been added in death surveillance system. The measures of training, supervision, check, sampling survey and telephone verifying were taken to increase death reporting rate and reduce data missing rate and underreporting rate. Multivariate logistic regression analysis was conducted to identify risk factors for smoking-attributed mortality. RESULTS: During the study period (2010 2014), the annual death reporting rates ranged from 6.50/00 to 7.00/00. The reporting rates of smoking status, smoking history and the number of cigarettes smoked daily were 95.53%, 98.63% and 98.58%, respectively. Compared with the nonsmokers, the RR of males was 1.38 (1.33-1.43) for all causes of death and 3.07 (2.91-3.24) for lung cancer due to smoking, the RR of females was 1.46 (1.39 1.54) for all causes of death and 4.07 (3.81-4.35) for lung cancer due to smoking, respectively. CONCLUSION: The study of smoking attributed mortality can be developed with less investment by using the stable and effective all causes of death surveillance system in Tianjin. PMID- 27005542 TI - [Association between HLA-DQ gene polymorphisms and different outcomes of hepatitis B virus infection]. AB - OBJECTIVE: To understand the association between two single-nucleotide polymorphism (HLA-DQ rs28567185 and rs9275572) and different outcomes of hepatitis B virus (HBV) infection. METHODS: A total of 825 HBV infection related cases were enrolled, and peripheral blood samples were collected from them for DNA extraction. The single-nucleotide polymorphism in HLA-DQ region were genotyped by using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Logistic regression analysis was conducted to evaluate the association between HLA-DQ gene polymorphism and different outcomes of hepatitis B virus infection. RESULTS: Our study indicated that cases with HLA-DQ rs2856718G (524 cases) and rs9275572A (369 cases) had reduced susceptibility to HBV infection (OR=0.702, 95%CI: 0.558-0.856, P=0.001; OR=0.548, 95%CI:0.365-0.847, P=0.005) and higher HBV natural clearance (OR=0.589, 95%CI: 0.478-0.892, P=8.81 * 10(-3); OR=0.673, 95%CI: 0.457-0.860, P=0.014). Moreover, rs9275572A was also associated with the lower risk of the development of hepatocellular carcinoma (OR=0.759, 95%CI: 0.538-0.914, P=0.041). CONCLUSION: Our study suggested that HLA DQ loci might be associated with the different outcomes of HBV infection in Chinese in Han ethnic group in northern China, rs2856718G and rs9275572A might be protective factors for HBV infection, HBV natural clearance and HBV-related disease progress. PMID- 27005543 TI - [Study on association between HLA-DP gene polymorphism and susceptibility to hepatitis B virus infection in minority population in Guizhou province]. AB - OBJECTIVE: To investigate the association between HLA-DP gene polymorphism and the susceptibility to hepatitis B virus (HBV) infection in people in Buyi, Miao and Shui ethnic groups in Guizhou. METHODS: A total of 256 patients with HBV infection, 142 HBV self-cleared patients and 135 controls were recruited from 3 ethnic groups for this case-control study. Genotypes of rs3077 and rs9277535 were determined by using real-time PCR with a TaqMan-MGB probe. RESULTS: Compared with healthy subjects and self-cleared subjects, the allele distribution of rs9277535 was significantly associated with chronic HBV infection (P<0.05), no significant differences in rs3077 allele and genotype distributions were found among 3 groups (P>0.05). Compared with the rs9277535 GG genotype, the AA and AG genotypes were protective factors against HBV infection in dominant model after adjustment for age and sex (OR=0.645, 95%CI: 0.421-0.988), and no significant difference in rs3077 locus was found in the same analysis (P>0.05). For men, the rs3077 locus CC and CT genotypes were also protective factors against HBV infection (OR=0.493, 95%CI: 0.266-0.916), and there was no significant difference in rs9277535 locus compared the genotype distributions among 3 groups in dominant mode. Comparison of allele and genotype distribution in 3 ethnic groups showed that HLA-DP gene rs3077 genotype distributions had significant difference between the HBV infection group and the healthy control group in Buyi ethnic group (chi(2)=6.726, P=0.036). CONCLUSIONS: The presence of rs9277535A allele atHLA-DP gene polymorphisms might decrease the risk for HBV infection, the rs3077 C allele at HLA-DP gene polymorphisms might also confer protective effect against HBV infection in women. No significant correlation between HLA-DP gene rs3077 and rs9277535 locus polymorphism and HBV clearance was found in this study. The HLA DP gene rs3077 genotype distribution of HBV-infected patients had significant differences among different ethnic groups. PMID- 27005544 TI - [Polymorphisms of toxin-antitoxin-chaperone system of Mycobacterium tuberculosis complex in China]. AB - OBJECTIVE: To investigate the single nucleotide polymorphism (SNP) of toxin antitoxin-chaperone (TAC) system of Mycobacterium (M.) tuberculosis with different genotypes and its biological significance. METHODS: A total of 183 clinical M. tuberculosis isolates were collected for spoligotyping. The sequences of higA,higB and Rv1957 were obtained by using PCR and DNA sequencing. The sequences were compared for possible mutations. Functional consequences of nonsynonymous SNPs were predicted by using I-Mutant 2.0 servers. RESULTS: Among the 183 M. tuberculosis isolates, 138(75.41%) belonged to the Beijing family, while 45(24.59%) belonged to the non-Beijing family. A total of 149(81.42%) isolates showed polymorphisms in the TAC system. We discovered 6 nonsynonymous SNPs and 2 synonymous SNPs. All the synonymous mutations occurred in higA gene, while nonsynonymous SNPs were found in the higA,higB and Rv1957 genes either. All the synonymous mutations and 4 nonsynonymous SNPs were restricted to the Beijing family strains and only 2 nonsynonymous SNPs were observed in the non-Beijing family strains. Of the 6 nonsynonymous SNPs studied, 4 were predicted to have ability to affect the stability of respective protein. CONCLUSION: The SNPs in the coding sequences of TAC system in clinical isolates can be relatively high and the Beijing family strains are with higher polymorphism, which might benefit to adapt to different host environment. PMID- 27005545 TI - [Molecular characteristics of dengue virus outbreak in China-Myanmar border region, Yunnan province, 2015]. AB - OBJECTIVE: To understand the molecular characteristics of a dengue virus outbreak in China-Myanmar border region, Yunnan province, 2015 and provide etiological evidence for the disease control and prevention. METHODS: Semi-nested RTPCR was conducted to detect the capsid premembrane (CprM) gene of RNA of dengue virus by using dengue virus NS1 positive serum samples collected in Mengdin township, Gengma county, Yunnan province in July, 2015. Some positive samples were then detected by using PCR with specific primers to amplify the full E gene. The positive PCR products were directly sequenced. Then sequences generated in this study were BLAST in NCBI website and aligned in Megalign in DNAstar program. Multiple sequence alignments were carried out by using Mega 5.05 software based on the sequences generated in this study and sequences downloaded from GenBank, including the representative strains from different countries and regions. Phylogenetic trees were constructed by using Neighbor-Joining tree methods with Mega 5.05 software. RESULTS: Twenty one of 25 local cases and 10 of 14 imported cases from Myanmar were positive for DENV-1. Eight serum samples were negative for dengue virus. A total of 13 strains with E gene (1485 bp), including 8 local strains and 5 imported strains, were sequenced, which shared 100% nucleotide sequence identities. Twelve strains with CprM gene (406 bp) from 9 local cases and 3 imported cases shared 100% nucleotide sequence identities. Phylogenetic analyses based on E gene showed that the new 13 strains clustered in genotype I of dengue virus and formed a distinct lineage. CONCLUSIONS: This outbreak was caused by genotype I of DENV-1, which had the closest phylogenetic relationships with dengue virus from neighboring Burma area. Comprehensive measures of prevention and control of dengue fever should be strengthened to prevent the spread of dengue virus. PMID- 27005546 TI - [Infection status and virulent genes of Aeromonas in diarrhea patients in Pudong New Area, Shanghai]. AB - OBJECTIVE: To investigate the infection status and virulent genes of Aeromonas in patients with acute diarrhea in Pudong New Area, Shanghai. METHODS: In 2012, stool samples were collected from diarrhea patients in 12 sentinel hospitals in Pudong for the detections of 13 pathogens causing diarrhea, and the detections of 5 diarrhea related virulent genes were conducted for Aeromonas isolates. RESULTS: A total of 101 patients were infected with Aeromonas in 2533 patients (4.0%). A total of 101 Aeromonas strains were isolated, including 17 Aeromonas hydrophila strains (18.8%), 44 Aeromonas veronii biovar sobria strains (52.5%) and 12 Aeromonas caviae strains (29.7%). And 44 coinfections with other pathogens were detected. Aeromonas infection mainly occurred in summer and in people aged >=20 years. Among the patients infected with Aeromonas, 71 (70.3%) had watery diarrhea, 20 (19.8%) had vomiting and 11 (10.9%) had fever. Virulent genes detection showed that 95.0% of the Aeromonas. strains carried virulent genes, and the detection rates of hlyA, aerA, act, alt, and ast genes were 5.9%, 6.9%, 67.3%, 42.6% and 13.9%, respectively. CONCLUSIONS: High incidence of Aeromonas infection was found in the patients with acute diarrhea in Pudong, and a high proportion of coinfections with other pathogens was detected too. Most Aeromonas strains carried virulent genes, and the distribution varied. PMID- 27005548 TI - [Epidemiology of intussusception related hospitalizations in children aged <2 years in Suzhou, 2007-2013]. AB - OBJECTIVE: To understand the epidemiological and clinical characteristics of <2 years old children hospitalized due to intussusceptions. METHODS: Clinical and demographic data of <2 years old children hospitalized due to intussusception between January 2007 and August 2013 were retrospectively collected in Affiliated Children' s Hospital of Soochow University in Suzhou. The incidence data, age distribution, seasonality and clinical characteristics of hospitalized intussusceptions cases were analyzed. RESULTS: A total of 594 intussusception related hospitalizations were identified during this period in children aged <2 years, no death occurred. The crude incidence of hospitalized intussusception was 57.3 per 100,000 in children aged <2 years (95%CI: 52.8-62.1), and 100.6 per 100,000 in children aged <1 year (95%CI: 92.1-109.8). The male to female ratio was 1.90:1. Up to 85.4% (507/594) of the cases were aged <1 year, and 66.2% (393/594) of the cases were aged 3-8 months. The incidence peaked in age group 5 8 months. The median age of the cases was 6.8 months (QR=4.4), and increased from 6.3 months (QR=4.2) in 2007 to 7.3 months (QR=4.0) in 2013. No obvious seasonality was observed. Main symptoms or signs included vomiting (83.2%, 494/594), abdominal mass (81.1%, 482/594), and bloody stool (64.5%, 383/594). Abdominal ultrasonic testing was the most frequently used diagnostic approach (98.7%, 586/594). Up to 86.2% (512/594) of patients were successfully treated by surgical intervention. The main sites for acute intussusception in children aged <2 years were ileocolic (34.5%, 183/530), ileo-ileo (30.8%, 163/530) or ileo-ileo colic (27.9%, 148/530). CONCLUSION: The incidence of hospitalized intussusception in children aged <2 years was high in Suzhou. It is necessary to establish an active surveillance system to provide baseline data for the evaluation of rotavirus vaccine safety. PMID- 27005547 TI - [Detection of neutralizing antibodies and DNA of human papillomavirus 16, 18 in women aged 18-45 years in Funing, Jiangsu province]. AB - OBJECTIVE: To understand the distributions of DNA and neutralizing antibodies of human papillomavirus (HPV)16, 18 in 18-45 year-old women. METHODS: Totally, 1494 women were enrolled through multistage random sampling in Funing, Jiangsu province. Cervical exfoliated cells were collected from them for HPV DNA testing, and serum samples were taken from them for the detection of HPV16, 18 neutralizing antibodies by using pseudovirion-based neutralization assay(PBNA). RESULTS: Among the 1494 women, 28(1.9%) and 188(12.6%) were positive for DNA and neutralizing antibody of HPV16 respectively, and 15(1.0%) and 60(4.0%) were positive for DNA and neutralizing antibody of HPV18, respectively. There were no significant differences in the detection rates of DNA and neutralizing antibody of HPV16, 18 among different age groups. About 16.7% of the women were infected with HPV16, 18, or both. CONCLUSION: In Funing county of Jiangsu province, most women aged 18-45 years has no immunity to HPV16 and 18, indicating that they are appropriate targets for HPV 16/18 vaccination. PMID- 27005549 TI - [Expression and clinical significance of kisspeptin-1, matrix metalloproteinase-2 and vascular endothelial growth factor in tissue of colon cancer]. AB - OBJECTIVE: To detect the expression of kisspeptin-1 (KISS-1), matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in the tissue of colon cancer, and analyze the relativity between KISS-1, MMP-2, VEGF and pathological characteristics of colon cancer. METHODS: A total of 60 colon cancer patients and 60 patients with benign colorectal disease who received surgical treatment in our hospital from January 2009 to June 2010 were selected as observation group and control group respectively. The cancer tissue samples and excision samples collected from them were used to detect KISS-1, MMP-2 and VEGF with immunohistochemistry. RESULTS: The positive rates of KISS-1, MMP-2 and VEGF were 31.7%, 58.3% and 78.3% in observation group, and 73.3%, 16.7% and 33.3% in control group. The positive rate of KISS-1 in observation group was lower than that in control group (chi(2)=23.489, P<0.001), and the positive rates of MMP-2 and VEGF in observation group were higher than those in control group (chi(2)=27.469, P<0.001; chi(2)=25.817, P<0.001). The expressions of KISS-1, MMP 2 and VEGF were significantly related with the histological grade and TNM stage of colon cancer (chi(2)=8.997, P=0.011; chi(2)=6.163, P=0.013; chi(2)=8.519, P=0.014; chi(2)=9.160, P=0.002; chi(2)=16.577, P<0.001; chi(2)=10.523, P=0.001). CONCLUSION: It is helpful to understand the differentiation and clinical stage of colon cancer and provide evidence for clinical diagnosis and prognosis prediction by detecting KISS-1, MMP-2 and VEGF. PMID- 27005550 TI - [Meta-analysis on relationship between Helicobacter pylori infection and esophagogastric junction adenocarcinoma]. AB - OBJECTIVE: To systematically evaluate the etiological association between esophagogastric junction adenocarcinoma and Helicobacter pylori (Hp) infection and the pathogenicity of Cag pathogenic island in Hp infection cases. METHODS: Literatures about Hp infection and esophagogastric junction adenocarcinoma published from January 1980 to April 2015 were retrieved from CNKI, Wanfang data, VIP, the Cochrane Library, PubMed, EMBase databases. The literatures which met the inclusion criteria were collected and evaluated by using Newcastle-Ottawa Scale, then the heterogeneity was analyzed with Review Manager 5.3, and the pooled OR value and 95% confidence interval were calculated. RESULTS: A total of 5547 study subjects were recruited in 13 studies, including 1446 esophagogastric junction adenocarcinoma cases and 4101 controls. The combined OR for Hp infection was 0.95 (95%CI: 0.66-1.36), P=0.71; The OR in high risk areas was 1.66 (95%CI: 1.33-2.08, P<0.001), higher than that in low-risk areas (0.68, 95%CI: 0.49-0.94, P=0.020). In addition, six studies found that the combined detection rates of Cag pathogenic island in esophagogastric junction adenocarcinoma cases and controls were 80.50% and 79.80%, respectively. There was no significant difference between two group, the combined OR was 1.24 (95%CI: 0.96-1.60). CONCLUSION: The association between Hp infection and esophagogastric junction adenocarcinoma was not significant, however, the significant difference was observed between high risk area and low risk area; the detection rate of Gag pathogenic island in Hp infection cases was high, but the pathogenicity for esophagogastric junction adenocarcinoma needs further study. PMID- 27005551 TI - [Variance estimation considering multistage sampling design in multistage complex sample analysis]. AB - Multistage sampling is a frequently-used method in random sampling survey in public health. Clustering or independence between observations often exists in the sampling, often called complex sample, generated by multistage sampling. Sampling error may be underestimated and the probability of type I error may be increased if the multistage sample design was not taken into consideration in analysis. As variance (error) estimator in complex sample is often complicated, statistical software usually adopt ultimate cluster variance estimate (UCVE) to approximate the estimation, which simply assume that the sample comes from one stage sampling. However, with increased sampling fraction of primary sampling unit, contribution from subsequent sampling stages is no more trivial, and the ultimate cluster variance estimate may, therefore, lead to invalid variance estimation. This paper summarize a method of variance estimation considering multistage sampling design. The performances are compared with UCVE and the method considering multistage sampling design by simulating random sampling under different sampling schemes using real world data. Simulation showed that as primary sampling unit (PSU) sampling fraction increased, UCVE tended to generate increasingly biased estimation, whereas accurate estimates were obtained by using the method considering multistage sampling design. PMID- 27005552 TI - [Study on early warning method for influenza epidemic in Gansu province]. AB - OBJECTIVE: To explore the appropriate early warning method for influenza epidemic in Gansu province. METHODS: By using simple control chart, moving percentile method, exponential smoothing method and cumulative sum control chart method, the annual incidence data of influenza-like illness in Gansu province during 2014 2015 were analyzed, and the sensitivities, specificities, positive predictive values, Jorden indexes and Kappa values of the 4 methods were evaluated and compared. RESULTS: The 2014-2015 seasonal influenza epidemic occurred in the fiftieth week of 2014 in Gansu, and the epidemic peak lasted for 6 weeks. Cumulative sum control chart method had the best early warning effect with the sensitivity of 66.67% and specificity of 93.48%. CONCLUSION: It is feasible to use cumulative sum control chart method to give early warning of influenza epidemic in Gansu. PMID- 27005553 TI - [Vaccination safety and media publicity strategy]. AB - Due to the over negative report of adverse event following immunization (AEFI) by media, some people began to question the safety of vaccination. Date published since 2005 were collected by literature retrieval, mainly including relative AEFI date, current status of media report of AEFI, public awareness about AEFI. Public concern about the vaccination safety mainly focused on the serious diseases which might be caused, influence on immune system. Media' s over negative reactions to AEFI and lack of related knowledge in general public have led to the public' s concern about vaccination safety. Vaccination is the most economical and effective measure for the prevention of diseases and AEFI incidence rate is very low. Therefore, it is necessary for media to give more positive report about vaccination safety. PMID- 27005554 TI - [Progress in research of pragmatic-explanatory continuum indicator summary]. AB - Randomized controlled trial (RCT) can be designed as explanatory trial and pragmatic/practical trial (PCT) for clinical effect evaluation. The pragmatic/practical trial reflects the intervention effect under actual clinical condition, which has relatively good extrapolation, but its internal validity is relatively poor. In contrast, explanatory trials conducted under ideal conditions have better inner validity but inferior external validity. However, in the design of RCT, PCT and explanatory trials are not always opposite. Many RCTs have the properties of the two designs at the same time, Pragmatic-explanatory continuum indicator summary (PRECIS) can be used in the design of RCT for the balance between internal validity and external validity. There are few available reports about the application of PRECIS in China at present, so this paper summarizes the basic principles, characteristics of PRECIS and the application of PRECIS in order to provide reference for the clinical trial design in China. PMID- 27005555 TI - Design and synthesis of 15-deoxyspergualin-biotin conjugates as novel binding probes for target protein screening. PMID- 27005556 TI - Small molecules modulating tumor-stromal cell interactions: new candidates for anti-tumor drugs. AB - The tumor microenvironment comprises tumor cells surrounding normal cells and the extracellular matrix. The surrounding normal cells have critical roles in the regulation of growth and metastasis of cancers, including the maintenance of cancer stem cells and the formation of cancer metastatic niches. Recent anti tumor strategies targeting the tumor microenvironment have included inhibition of angiogenesis and the augmentation of immune reactions. However, in this review, we will focus on stromal cells (fibroblast-like cells), a common constituent of the tumor microenvironment. Since stromal cells regulate the growth of cancer cells positively and negatively through adhesion and secreted factors, anti-tumor strategies should consider modulating tumor-stromal cell interactions through use of small molecules. PMID- 27005557 TI - New conjugates of polyene macrolide amphotericin B with benzoxaboroles: synthesis and properties. AB - A novel series of conjugates of the antifungal antibiotic amphotericin B (AmB) with benzoxaboroles was synthesized. Antifungal activity of new compounds was tested on yeastbeta Candida albicans and Cryptococcus humicolus and filamentous fungi Aspergillus niger and Fusarium oxysporum using the broth microdilution method. The potency of di-modified derivatives against the tested strains was similar to that of the parent AmB. New derivatives demonstrated differential toxicity against human cells (colon epithelium or red blood cells). The di modified conjugate 2-(N,N-dimethylamino)ethylamide of 3'-N-[3-(1-hydroxy-1,3 dihydrobenzo[c][1,2]oxaborol-7-yl)propanoyl] AmB (9) showed the best combination of a high antifungal activity with a low cytotoxic and hemolytic potency. PMID- 27005558 TI - Onset of the Electronic Absorption Spectra of Isolated and pi-Stacked Oligomers of 5,6-Dihydroxyindole: An Ab Initio Study of the Building Blocks of Eumelanin. AB - Eumelanin is a naturally occurring skin pigment which is responsible for developing a suntan. The complex structure of eumelanin consists of pi-stacked oligomers of various indole derivatives, such as the monomeric building block 5,6 dihydroxyindole (DHI). In this work, we present an ab initio wave-function study of the absorption behavior of DHI oligomers and of doubly and triply pi-stacked species of these oligomers. We have simulated the onset of the electronic absorption spectra by employing the MP2 and the linear-response CC2 methods. Our results demonstrate the effect of an increasing degree of oligomerization of DHI and of an increasing degree of pi-stacking of DHI oligomers on the onset of the absorption spectra and on the degree of red-shift toward the visible region of the spectrum. We find that pi-stacking of DHI and its oligomers substantially red shifts the onset of the absorption spectra. Our results also suggest that the optical properties of biological eumelanin cannot be simulated by considering the DHI building blocks alone, but instead the building blocks indole-semiquinone and indole-quinone have to be considered as well. This study contributes to advancing the understanding of the complex photophysics of the eumelanin biopolymer. PMID- 27005559 TI - Amplification of WHSC1L1 regulates expression and estrogen-independent activation of ERalpha in SUM-44 breast cancer cells and is associated with ERalpha over expression in breast cancer. AB - The 8p11-p12 amplicon occurs in approximately 15% of breast cancers in aggressive luminal B-type tumors. Previously, we identified WHSC1L1 as a driving oncogene from this region. Here, we demonstrate that over-expression of WHSC1L1 is linked to over-expression of ERalpha in SUM-44 breast cancer cells and in primary human breast cancers. Knock-down of WHSC1L1, particularly WHSC1L1-short, had a dramatic effect on ESR1 mRNA and ERalpha protein levels. SUM-44 cells do not require exogenous estrogen for growth in vitro; however, they are dependent on ERalpha expression, as ESR1 knock-down or exposure to the selective estrogen receptor degrader fulvestrant resulted in growth inhibition. ChIP-Seq experiments utilizing ERalpha antibodies demonstrated extensive ERalpha binding to chromatin in SUM-44 cells under estrogen-free conditions. ERalpha bound to ERE and FOXA1 motifs under estrogen-free conditions and regulated expression of estrogen responsive genes. Short-term treatment with estradiol enhanced binding of ERalpha to chromatin and influenced expression of many of the same genes to which ERalpha was bound under estrogen-free conditions. Finally, knock-down of WHSC1L1 in SUM 44 cells resulted in loss of ERalpha binding to chromatin under estrogen-free conditions, which was restored upon exposure to estradiol. These results indicate the SUM-44 cells are a good model of a subset of luminal B breast cancers that have the 8p11-p12 amplicon, over-express WHSC1L1, and over-express ERalpha, but are independent of estrogen for binding to chromatin and regulation of gene expression. Breast cancers such as these, that are dependent on ERalpha activity but independent of estradiol, are a major cause of breast cancer mortality. PMID- 27005560 TI - Different physical forms of one diet fed to growing pigs induce morphological changes in mandubular glands and local leptin (Ob) production and receptor (ObR) expression. AB - The physical form of the diet plays an important role for morphological adaptations of organs in the gastrointestinal tract. It was hypothesized that different physical forms of one diet could exert extra-enteric effects, under local and systemic neuroendocrine regulation. Gross morphology, fresh mass and cytoarchitecture of mandibular glands (MG) were studied in growing pigs fed with one diet processed under four different physical forms. Four dietary treatments were offered for 4 weeks to 32 growing pigs (initial BW: 8.30 +/- 0.83 kg) allotted into 4 experimental groups: FP, finely ground pellet (dMean, 0.46 mm); CM, coarsely ground meal (dMean, 0.88 mm); CP, coarsely ground pellet (dMean, 0.84); CE, coarsely ground extruded (dMean, 0.66). Conventional and immuonohistochemical techniques were used to immunolocalize, in particular, leptin (Ob) and its receptor (ObR). A significant effect was observed on the relative mass of the MG, depending on the diet (p < 0.03) and on the BW (p < 0.04), with no interactions (diet*BW). The immunohistochemical reactions for Ob and ObR showed a marked positivity in the MG from the group fed with the CM diet, displaying Ob-positive acinar cells and ObR-positive cells in the striated ducts, together with endocrine-like cells. The intensity of chromogenic reactions positively testing to ObR was used to evaluate the cytoarchitecture of the MG and its possible correlations. Pearson's correlation coefficient resulted to positively link (p < 0.0001) the ObR expression with the absolute mass of MG in the 61.1% of pigs. The physical form of the diet is related to extra-enteral effects, inducing changes in gross and microscopic morphology of the MG in the growing pig. The local production of Ob and the expression of the respective ObR in the striated duct cells shed a new light on the mitogenic activity of Ob in extra-enteral organs, like the MG, in relation to the physical form of the diet. PMID- 27005561 TI - Sensitive, automatic method for the determination of diazepam and its five metabolites in human oral fluid by online solid-phase extraction and liquid chromatography with tandem mass spectrometry. AB - A novel and simple online solid-phase extraction liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of diazepam and its five metabolites including nordazepam, oxazepam, temazepam, oxazepam glucuronide, and temazepam glucuronide in human oral fluid. Human oral fluid was obtained using the Salivette((r)) collection device, and 100 MUL of oral fluid samples were loaded onto HySphere Resin GP cartridge for extraction. Analytes were separated on a Waters Xterra C18 column and quantified by liquid chromatography with tandem mass spectrometry using the multiple reaction monitoring mode. The whole procedure was automatic, and the total run time was 21 min. The limit of detection was in the range of 0.05-0.1 ng/mL for all analytes. The linearity ranged from 0.25 to 250 ng/mL for oxazepam, and 0.1 to 100 ng/mL for the other five analytes. Intraday and interday precision for all analytes was 0.6-12.8 and 1.0-9.2%, respectively. Accuracy ranged from 95.6 to 114.7%. Method recoveries were in the range of 65.1-80.8%. This method was fully automated, simple, and sensitive. Authentic oral fluid samples collected from two volunteers after consuming a single oral dose of 10 mg diazepam were analyzed to demonstrate the applicability of this method. PMID- 27005562 TI - Organophotocatalysis: Insights into the Mechanistic Aspects of Thiourea-Mediated Intermolecular [2+2] Photocycloadditions. AB - Mechanistic investigations of the intermolecular [2+2] photocycloaddition of coumarin with tetramethylethylene mediated by thiourea catalysts reveal that the reaction is enabled by a combination of minimized aggregation, enhanced intersystem crossing, and altered excited-state lifetime(s). These results clarify how the excited-state reactivity can be manipulated through catalyst substrate interactions and reveal a third mechanistic pathway for thiourea mediated organo-photocatalysis. PMID- 27005563 TI - The Complexity of Simplicity: Role of Sex, Development and Environment in the Modulation of the Stress Response. AB - Anecdotally, we all know that stress is 'complicated', although most stress research is undertaken using incredibly simplified models that may not allow us to fully understand the underlying interactive mechanisms present in the 'real world'. This attempt at simplification, although sometimes necessary, may explain some of the difficulties faced when integrating basic science findings with the clinical and epidemiological data on stress and stress-related disorders. In a symposium held at the 2015 International Society for Psychoneuroendocrinology meeting in Edinburgh, UK, a series of speakers explored 'The Many Pathways to Plasticity in the Stress System', specifically focusing on variables that, in many cases, are eliminated from studies of stress to provide increased experimental control. Specifically, four speakers tackled the complex contributions of 'Sex, Development and Environment' in stress research, and reported published and unpublished evidence from work conducted in their own laboratories demonstrating that, in our race for simplicity in experimentation, the stories that we tell become all the more complex. PMID- 27005564 TI - Effect of case management on glycemic control and behavioral outcomes for chinese people with type 2 diabetes: A 2-year study. AB - OBJECTIVE: To examine the effect of case management on glycemic control and behavioral outcomes in adults with Type 2 diabetes in China. METHODS: Participants were randomly assigned to a 1-year case management (CM) group (n=60) or control group (n=60). Monthly case management visits included identifying individuals' diabetes-related problems, setting goals, planning self-care, and evaluating progress. During a 1-year follow-up, all participants attended visits every 3 months without intervention. RESULTS: In the CM vs. the control group, HbA1c was reduced at 6 months compared to baseline (P=0.034), with trends at 12 and 24 months, and empowerment ability improved (P<0.05). Also in the CM vs. controls, total self-care behaviors, the frequency of exercise, blood glucose testing, and foot care were higher (P<0.001) at 12 months, and the percentage of individuals with HbA1c <=7.0% was higher (P=0.035) at 24 months. CONCLUSION: The case management intervention in China was effective at 6 months and, based on trends in HbA1c at 12 and 24 months and results for behavioral outcomes, the intervention shows promise and warrants more research. PRACTICE IMPLICATIONS: A case management approach can enhance behavior change and glycemic control in Chinese with diabetes. PMID- 27005565 TI - Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database. AB - OBJECTIVE: To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression. DESIGN: Cohort study. SETTING: UK general practices contributing to the QResearch primary care database. PARTICIPANTS: 238,963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011. EXPOSURES: Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs. MAIN OUTCOME MEASURES: First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years' follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables. RESULTS: During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years' follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years' follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses >= 40 mg/day). CONCLUSIONS: This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine. PMID- 27005566 TI - Population-genetic properties of differentiated copy number variations in cattle. AB - While single nucleotide polymorphism (SNP) is typically the variant of choice for population genetics, copy number variation (CNV) which comprises insertion, deletion and duplication of genomic sequence, is an informative type of genetic variation. CNVs have been shown to be both common in mammals and important for understanding the relationship between genotype and phenotype. However, CNV differentiation, selection and its population genetic properties are not well understood across diverse populations. We performed a population genetics survey based on CNVs derived from the BovineHD SNP array data of eight distinct cattle breeds. We generated high resolution results that show geographical patterns of variations and genome-wide admixture proportions within and among breeds. Similar to the previous SNP-based studies, our CNV-based results displayed a strong correlation of population structure and geographical location. By conducting three pairwise comparisons among European taurine, African taurine, and indicine groups, we further identified 78 unique CNV regions that were highly differentiated, some of which might be due to selection. These CNV regions overlapped with genes involved in traits related to parasite resistance, immunity response, body size, fertility, and milk production. Our results characterize CNV diversity among cattle populations and provide a list of lineage-differentiated CNVs. PMID- 27005567 TI - Nasal balloon autoinflation can help clear middle ear effusion, improving the quality of life in school-aged children with glue ear. PMID- 27005569 TI - Numerical simulation of vascular tumour growth under antiangiogenic treatment: addressing the paradigm of single-agent bevacizumab therapy with the use of experimental data. AB - BACKGROUND: Antiangiogenic agents have been recently added to the oncological armamentarium with bevacizumab probably being the most popular representative in current clinical practice. The elucidation of the mode of action of these agents is a prerequisite for personalized prediction of antiangiogenic treatment response and selection of patients who may benefit from this kind of therapy. To this end, having used as a basis a preexisting continuous vascular tumour growth model which addresses the targeted nature of antiangiogenic treatment, we present a paper characterized by the following three features. First, the integration of a two-compartmental bevacizumab specific pharmacokinetic module into the core of the aforementioned preexisting model. Second, its mathematical modification in order to reproduce the asymptotic behaviour of tumour volume in the theoretical case of a total destruction of tumour neovasculature. Third, the exploitation of a range of published animal datasets pertaining to antitumour efficacy of bevacizumab on various tumour types (breast, lung, head and neck, colon). RESULTS: Results for both the unperturbed growth and the treatment module reveal qualitative similarities with experimental observations establishing the biologically acceptable behaviour of the model. The dynamics of the untreated tumour has been studied via a parameter analysis, revealing the role of each relevant input parameter to tumour evolution. The combined effect of endogenous proangiogenic and antiangiogenic factors on the angiogenic potential of a tumour is also studied, in order to capture the dynamics of molecular competition between the two key-players of tumoural angiogenesis. The adopted methodology also allows accounting for the newly recognized direct antitumour effect of the specific agent. CONCLUSIONS: Interesting observations have been made, suggesting a potential size-dependent tumour response to different treatment modalities and determining the relative timing of cytotoxic versus antiangiogenic agents administration. Insight into the comparative effectiveness of different antiangiogenic treatment strategies is revealed. The results of a series of in vivo experiments in mice bearing diverse types of tumours (breast, lung, head and neck, colon) and treated with bevacizumab are successfully reproduced, supporting thus the validity of the underlying model. PMID- 27005570 TI - Calcium Pill Aspiration. PMID- 27005571 TI - Predicting multi-class responses to preoperative chemoradiotherapy in rectal cancer patients. AB - BACKGROUND: Preoperative chemoradiotherapy (CRT) has become a widely used treatment for improving local control of disease and increasing survival rates of rectal cancer patients. We aimed to identify a set of genes that can be used to predict responses to CRT in patients with rectal cancer. METHODS: Gene expression profiles of pre-therapeutic biopsy specimens obtained from 77 rectal cancer patients were analyzed using DNA microarrays. The response to CRT was determined using the Dworak tumor regression grade: grade 1 (minimal, MI), grade 2 (moderate, MO), grade 3 (near total, NT), or grade 4 (total, TO). RESULTS: Top ranked genes for three different feature scores such as a p-value (pval), a rank product (rank), and a normalized product (norm) were selected to distinguish pre defined groups such as complete responders (TO) from the MI, MO, and NT groups. Among five different classification algorithms, supporting vector machine (SVM) with the top 65 norm features performed at the highest accuracy for predicting MI using a 5-fold cross validation strategy. On the other hand, 98 pval features were selected for predicting TO by elastic net (EN). Finally we combined TO- and MI-finder models to build a three-class classification model and validated it using an independent dataset of rectal cancer mRNA expression. CONCLUSIONS: We identified MI- and TO-finders for predicting preoperative CRT responses, and validated these data using an independent public dataset. This stepwise prediction model requires further evaluation in clinical studies in order to develop personalized preoperative CRT in patients with rectal cancer. PMID- 27005572 TI - Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance. AB - BACKGROUND: Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance. METHODS: To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods. RESULTS: The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites. CONCLUSIONS: Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance mutations to improve the design of tuberculosis control measures, such as diagnostics, and inform patient management. PMID- 27005573 TI - Differential expression of Spiroplasma citri surface protein genes in the plant and insect hosts. AB - BACKGROUND: Spiroplasma citri is a cell wall-less, plant pathogenic bacteria that colonizes two distinct hosts, the leafhopper vector and the host plant. Given the absence of a cell wall, surface proteins including lipoproteins and transmembrane polypeptides are expected to play key roles in spiroplasma/host interactions. Important functions in spiroplasma/insect interactions have been shown for a few surface proteins such as the major lipoprotein spiralin, the transmembrane S. citri adhesion-related proteins (ScARPs) and the sugar transporter subunit Sc76. S. citri efficient transmission from the insect to the plant is expected to rely on its ability to adapt to the different environments and more specifically to regulate the expression of genes encoding surface-exposed proteins. RESULTS: Genes encoding S. citri lipoproteins and ScARPs were investigated for their expression level in axenic medium, in the leafhopper vector Circulifer haematoceps and in the host plant (periwinkle Catharanthus roseus) either insect infected or graft-inoculated. The vast majority of the lipoprotein genes tested (25/28) differentially responded to the various host environments. Considering their relative expression levels in the different environments, the possible involvement of the targeted genes in spiroplasma host adaptation was discussed. In addition, two S. citri strains differing notably in their ability to express adhesin ScARP2b and pyruvate dehydrogenase E1 component differed in their capacity to multiply in the two hosts, the plant and the leafhopper vector. CONCLUSIONS: This study provided us with a list of genes differentially expressed in the different hosts, leading to the identification of factors that are thought to be involved in the process of S. citri host adaptation. The identification of such factors is a key step for further understanding of S. citri pathogenesis. Moreover the present work highlights the high capacity of S. citri in tightly regulating the expression level of a large set of surface protein genes, despite the small size of its genome. PMID- 27005574 TI - Effect of SSRIs and SNRIs on Nocturnal Urinary Frequency. AB - BACKGROUND: Existing data suggest that selective serotonin uptake inhibitors (SSRIs) may have an impact on urinary frequency. OBJECTIVE: To evaluate the impact of SSRIs and selective noradrenaline reuptake inhibitors (SNRIs) on nocturnal urinary frequency. METHODS: This was a retrospective study comparing nocturnal urinary frequency in individuals on SSRI or SNRI therapy versus no therapy during nocturnal polysomnography in a 14-month period at a sleep center. RESULTS: A total of 316 individuals were studied: 94 in the SSRI/SNRI group and 222 controls. No statistically significant difference was found in nocturnal urinary frequency between those on SSRI/SNRI therapy and the control group (0.40 vs 0.34 bathroom visits/night, P = 0.40). The degree of urinary frequency was higher in sertraline users (0.61 bathroom visits/night) compared with duloxetine users (0.18 visits/night, 2-tailed P = 0.04). A post hoc analysis suggested that the difference between these 2 agents is a class effect (SSRIs vs SNRIs, 2-tailed P = 0.03). The sample size did not allow conclusive comparison of either the SSRI or the SNRI group with the control group. CONCLUSION: SSRI/SNRI agents as a combined group do not appear to have a significant impact on nocturnal urinary frequency. The SSRIs and SNRIs may have an opposite effect on nocturnal frequency. PMID- 27005575 TI - PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. AB - OBJECTIVE: To develop an evidence-based guideline for Peer Review of Electronic Search Strategies (PRESS) for systematic reviews (SRs), health technology assessments, and other evidence syntheses. STUDY DESIGN AND SETTING: An SR, Web based survey of experts, and consensus development forum were undertaken to identify checklists that evaluated or validated electronic literature search strategies and to determine which of their elements related to search quality or errors. RESULTS: Systematic review: No new search elements were identified for addition to the existing (2008-2010) PRESS 2015 Evidence-Based Checklist, and there was no evidence refuting any of its elements. Results suggested that structured PRESS could identify search errors and improve the selection of search terms. Web-based survey of experts: Most respondents felt that peer review should be undertaken after the MEDLINE search had been prepared but before it had been translated to other databases. Consensus development forum: Of the seven original PRESS elements, six were retained: translation of the research question; Boolean and proximity operators; subject headings; text word search; spelling, syntax and line numbers; and limits and filters. The seventh (skilled translation of the search strategy to additional databases) was removed, as there was consensus that this should be left to the discretion of searchers. An updated PRESS 2015 Guideline Statement was developed, which includes the following four documents: PRESS 2015 Evidence-Based Checklist, PRESS 2015 Recommendations for Librarian Practice, PRESS 2015 Implementation Strategies, and PRESS 2015 Guideline Assessment Form. CONCLUSION: The PRESS 2015 Guideline Statement should help to guide and improve the peer review of electronic literature search strategies. PMID- 27005576 TI - 2015 Legislative update of e-cigarette youth access and exposure laws. AB - BACKGROUND: As of November 15, 2013, 22 states had passed laws explicitly addressing youth access to electronic cigarettes (e-cigarettes); by 2014, this increased to 41 states. Also in 2014, more than 13.4% of youth in the U.S. reported using e-cigarettes, making e-cigarette use more prevalent than conventional cigarette use (9.2%). METHODS: We examined 221 bills addressing youth access and exposure to e-cigarettes between January 1 and November 1, 2015. Text searches on individual state general assembly websites and secondary sources were employed for data collection. Laws were analyzed using seven measures identified to protect adolescents from nicotine initiation and use. RESULTS: Two states (MI, PA) and Washington D.C. do not regulate the sale or distribution of e cigarettes to youth as of November 1, 2015. Additionally, seventeen states have passed laws requiring e-cigarettes to use child-safety packaging to minimize unintended poisoning. As of July 1, 2016, four states (KS, LA, MN, and NC) will tax e-cigarettes. Oregon prohibits the use of e-cigarettes in cars with children under 18years of age, and Wyoming requires the public health department to develop educational campaigns to better educate the state on the risks of nicotine and tobacco products. CONCLUSION: While states are closing the gap of youth nicotine exposure, there remains a need to protect youth from e-cigarettes access, which can cause adverse health effects of brain development, lung function and potentially lead to addiction. Recommendation for the FDA to regulate e-cigarettes federally would close this regulation gap and protect youth across the U.S. PMID- 27005577 TI - Parasite diversity drives rapid host dynamics and evolution of resistance in a bacteria-phage system. AB - Host-parasite evolutionary interactions are typically considered in a pairwise species framework. However, natural infections frequently involve multiple parasites. Altering parasite diversity alters ecological and evolutionary dynamics as parasites compete and hosts resist multiple infection. We investigated the effects of parasite diversity on host-parasite population dynamics and evolution using the pathogen Pseudomonas aeruginosa and five lytic bacteriophage parasites. To manipulate parasite diversity, bacterial populations were exposed for 24 hours to either phage monocultures or diverse communities containing up to five phages. Phage communities suppressed host populations more rapidly but also showed reduced phage density, likely due to interphage competition. The evolution of resistance allowed rapid bacterial recovery that was greater in magnitude with increases in phage diversity. We observed no difference in the extent of resistance with increased parasite diversity, but there was a profound impact on the specificity of resistance; specialized resistance evolved to monocultures through mutations in a diverse set of genes. In summary, we demonstrate that parasite diversity has rapid effects on host parasite population dynamics and evolution by selecting for different resistance mutations and affecting the magnitude of bacterial suppression and recovery. Finally, we discuss the implications of phage diversity for their use as biological control agents. PMID- 27005579 TI - Acquisition of choice in concurrent chains: Assessing the cumulative decision model. AB - Concurrent chains is widely used to study pigeons' choice between terminal links that can vary in delay, magnitude, or probability of reinforcement. We review research on the acquisition of choice in this procedure. Acquisition has been studied with a variety of research designs, and some studies have incorporated no food trials to allow for timing and choice to be observed concurrently. Results show that: Choice can be acquired rapidly within sessions when terminal links change unpredictably; under steady-state conditions, acquisition depends on both initial- and terminal-link schedules; and initial-link responding is mediated by learning about the terminal-link stimulus-reinforcer relations. The cumulative decision model (CDM) proposed by Christensen and Grace (2010) and Grace and McLean (2006, 2015) provides a good description of within-session acquisition, and correctly predicts the effects of initial and terminal-link schedules in steady-state designs (Grace, 2002a). Questions for future research include how abrupt shifts in preference within individual sessions and temporal control of terminal-link responding can be modeled. PMID- 27005578 TI - Synthesis and Biological Evaluation of New (-)-Englerin Analogues. AB - We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC). PMID- 27005580 TI - National Survey on the Impact of Viral Testing for the ED and Inpatient Management of Febrile Young Infants. AB - OBJECTIVE: Well-appearing febrile infants with viral illnesses cannot be distinguished from those with occult life-threatening infections. Infants with respiratory viruses are less likely to have serious bacterial infections; however, current risk-stratification criteria predate widespread viral testing and there are limited data to safely inform physician management with this now common diagnostic tool. This study sought to explore the possible impact of respiratory virus testing on clinical decision-making for the management of febrile young infants<6 weeks old. METHODS: A scenario-based survey was sent to emergency department (ED) and inpatient physicians at all 16 Canadian tertiary pediatric centers. Participants were asked questions regarding management decisions with and without results of respiratory virus testing. RESULTS: Response rate was 78% (n=330; 190 ED, 140 inpatient). Detection of a respiratory virus reduced admission rates among 3-week-old (83% vs 95%, P<.001) and 5-week old infants (36% vs 52%, P<.001). Similarly, empirical antibiotic treatment was decreased by detection of a respiratory virus for 3-week-old (65% vs 92%, P<.001) and 5-week-old infants (25% vs 39%, P<.001). Management of 5-week-old infants differed between ED and inpatient physicians, both in the presence and absence of a respiratory virus. There was no consensus among inpatient physicians regarding admission duration for well infants with a detectable respiratory virus and otherwise negative workup. CONCLUSIONS: Respiratory virus testing appears to influence clinical decision-making for febrile infants<6 weeks, reducing both rates of admission and antimicrobial treatment. Important work is needed to better understand how to safely incorporate viral testing for the management of this vulnerable patient population. PMID- 27005581 TI - Rapid expulsion of microswimmers by a vortical flow. AB - Interactions of microswimmers with their fluid environment are exceptionally complex. Macroscopic shear flow alters swimming trajectories in a highly nontrivial way and results in dramatic reduction of viscosity and heterogeneous bacterial distributions. Here we report on experimental and theoretical studies of rapid expulsion of microswimmers, such as motile bacteria, by a vortical flow created by a rotating microparticle. We observe a formation of a macroscopic depletion area in a high-shear region, in the vicinity of a microparticle. The rapid migration of bacteria from the shear-rich area is caused by a vortical structure of the flow rather than intrinsic random fluctuations of bacteria orientations, in stark contrast to planar shear flow. Our mathematical model reveals that expulsion is a combined effect of motility and alignment by a vortical flow. Our findings offer a novel approach for manipulation of motile microorganisms and shed light on bacteria-flow interactions. PMID- 27005582 TI - HLA-A*33:102, a novel allele identified by sequence-based typing in cord blood from a Korean woman. AB - The new allele A*33:102 showed two nucleotide differences with A*33:03:01 in exon 3. PMID- 27005583 TI - Current Uses of Beta-Diversity in Biodiversity Conservation: A response to Socolar et al. PMID- 27005584 TI - Attitudes on first aid for paediatric burns: Pilot survey of a developed city state. AB - INTRODUCTION: Burn-related injuries are prevalent worldwide. Caregiver first aid can mitigate the devastating effects of paediatric burn injuries. Our aim was to assess knowledge of paediatric burns first aid among caregivers and determine whether knowledge levels can be raised following a short educational intervention. METHOD: Over a 13-week period we surveyed 274 caregivers at the children's emergency department of KK Women's and Children's Hospital. The questionnaire assessed caregiver demographics and knowledge of burn first aid pre intervention. There was an educational interlude during which the moderator educated the caregiver using a simple pictorial guide. The survey resumed thereafter and the post-intervention questions were completed. RESULTS: Of the 274 surveys conducted, 272 complete responses were obtained. We found a substantial and statistically significant increase in knowledge of caregivers immediately following the intervention. Two statistically significant predictors of adequate post-interventional scores were the caregivers' highest educational level and their total score in the pre-interventional assessment. Caregivers who scored well in the post-intervention questionnaire relied on school (p=0.013) and the Internet (p=0.130) as sources of information on burns first aid. Caregivers without prior personal experience with burns tended to fare better in the post interventional survey. CONCLUSION: Our study shows it is possible to correct knowledge gaps in the immediate period through a simple pictorial guide. Our study also identified a structure for a focused national educational campaign. PMID- 27005585 TI - Spatial analysis of pediatric burns shows geographical clustering of burns and 'hotspots' of risk factors in New South Wales, Australia. AB - OBJECTIVE: Pediatric burns are a significant cause of morbidity and mortality, and it is estimated that more than 80% are preventable. Studies among adults have shown that burns risk are geographically clustered, and higher in socioeconomically-disadvantaged areas. Few studies among children have examined whether burns are geographically clustered, and if burn prevention programs are best targeted to high-risk areas. METHOD: Retrospective analyses examined the 2005-to-2014 NSW Severe Burns Injury Service data. Geospatial imaging software was used to map the relative-risk and clustering of burns by postcodes in Greater Sydney Area (GSA). Cluster analyses were conducted using Getis-Ord and Global Moran's I statistics. High- and low-risk populations and areas were examined to ascertain differences by sociodemographic characteristics, etiology and the extent of the burn. RESULTS: Scalds were the most common types of burns and boys were at greater risk than girls. There was significant clustering of burns by postcode area, with a higher relative risk of burns in western and north-western areas of Sydney. The high-risk clusters were associated with socioeconomic disadvantage, and areas of low burns risk were associated with socioeconomic advantage. In both high- and low-risk areas burns occurred more frequently in the 12-24 months and the 24-36 months age groups. The implication of this study is that pediatric burns risk clustering occurs in specific geographic regions that are associated with socioeconomic disadvantage. The results of this study provide greater insight into how pediatric populations can be targeted when devising intervention strategies, and suggest that an area-targeted approach in socioeconomically-disadvantaged areas may reduce burns risk. PMID- 27005586 TI - Investigating the phenomenology of imagery following traumatic burn injuries. AB - Intrusive images related to adverse experiences are an important feature of a number of psychological disorders and a hallmark symptom of posttraumatic stress disorder (PTSD). Depression, anxiety, and PTSD are all common reactions following a burn injury. However, the nature of burn-related trauma memories and associated intrusions and their contribution to psychological disorders is not well understood. The aim of the study was to take a broad look at the nature of imagery experienced by people who have sustained a burn injury. Nineteen participants completed self-report questionnaires assessing depression, anxiety, and PTSD symptoms and were administered a semi-structured interview which explored the characteristics (vividness, sensory modalities, intrusions, emotion intensity) of imagery formed in relation to their burn injuries. Ongoing intrusive imagery was reported by over half the participants and there were significant correlations between frequency of intrusive images and posttraumatic symptoms, and between intensity of emotions associated with intrusive images and depression and posttraumatic symptoms. A thematic analysis of the memory narratives revealed four main themes: threat to self, view of the world, view of others, and positive psychological change. These results are discussed in relation to existing trauma theory and burn injury literature. Implications for clinical practice and recommendations for further research are proposed. PMID- 27005587 TI - Brain-gut-microbiota axis: challenges for translation in psychiatry. AB - PURPOSE: The accruing data linking the gut microbiome to the development and function of the central nervous system has been proposed as a paradigm shift in neuroscience. The gut microbiota can communicate with the brain via neuroimmune, neuroendocrine, and neural pathways comprising the brain-gut-microbiota axis. Dysfunctional neuroimmune pathways are implicated in stress-related psychiatric disorders. METHODS: Using depression as our primary example, we review both the preclinical and clinical evidence supporting the possible role played by the gut microbiota in stress-related psychiatric disorders. We consider how this can inform future treatment strategies and outline the challenges and necessary studies for moving the field forward. RESULTS: The role played by the gut microbiota has not been fully elucidated in psychiatric populations. Although tempting to speculate that psychiatric patients may benefit from therapeutic modulation of the brain-gut-microbiota axis, the translational applications of the results obtained in rodent studies have yet to be demonstrated. CONCLUSIONS: Evidence of altered gut microbiota composition and function in psychiatric patients is limited and cannot be regarded as proven. Moreover the efficacy of targeting the gut microbiota has not yet been established, and needs further investigation. PMID- 27005588 TI - A Risk Radar driven by Internet of intelligences serving for emergency management in community. AB - Today, most of the commercial risk radars only have the function to show risks, as same as a set of risk matrixes. In this paper, we develop the Internet of intelligences (IOI) to drive a risk radar monitoring dynamic risks for emergency management in community. An IOI scans risks in a community by 4 stages: collecting information and experience about risks; evaluating risk incidents; verifying; and showing risks. Employing the information diffusion method, we optimized to deal with the effective information for calculating risk value. Also, a specific case demonstrates the reliability and practicability of risk radar. PMID- 27005589 TI - Serratia marcescens bacteremia cases: A pseudo-outbreak experience. PMID- 27005590 TI - Transitive closure of subsumption and causal relations in a large ontology of radiological diagnosis. AB - The Radiology Gamuts Ontology (RGO)-an ontology of diseases, interventions, and imaging findings-was developed to aid in decision support, education, and translational research in diagnostic radiology. The ontology defines a subsumption (is_a) relation between more general and more specific terms, and a causal relation (may_cause) to express the relationship between disorders and their possible imaging manifestations. RGO incorporated 19,745 terms with their synonyms and abbreviations, 1768 subsumption relations, and 55,558 causal relations. Transitive closure was computed iteratively; it yielded 2154 relations over subsumption and 1,594,896 relations over causality. Five causal cycles were discovered, all with path length of no more than 5. The graph-theoretic metrics of in-degree and out-degree were explored; the most useful metric to prioritize modification of the ontology was found to be the product of the in-degree of transitive closure over subsumption and the out-degree of transitive closure over causality. Two general types of error were identified: (1) causal assertions that used overly general terms because they implicitly assumed an organ-specific context and (2) subsumption relations where a site-specific disorder was asserted to be a subclass of the general disorder. Transitive closure helped identify incorrect assertions, prioritized and guided ontology revision, and aided resources that applied the ontology's knowledge. PMID- 27005592 TI - Nitrogen removal from old landfill leachate with SNAP technology using biofix as a biomass carrier. AB - Single-stage nitrogen removal using Anammox and partial nitritation (SNAP) is a novel technology developed in recent years for removing nitrogen. To evaluate the ability of SNAP technology to remove nitrogen in old landfill leachate under the conditions in Vietnam, we conducted a survey with 7 different nitrogen loading rates of 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4 kg-N/m(3) day and a concentration from 100 to 700 mg-N/L. The operating conditions were as follows: DO at 1.0-5.3 mg/L, HRT at 12 h, and pH at 7.5-7.8. The biomass carrier was a biofix made from acrylic fiber. The maximum ammonium conversion and nitrogen removal efficiency were approximately 98% and 85%, respectively, at 1.2 kg-N/m(3) day. In general, the nitrogen removal efficiency increased and stabilized at the end of each loading rate. The first step showed that SNAP could potentially be applied in real life for removing nitrogen from old landfill leachate. PMID- 27005591 TI - Predicting reinterventions after open and endovascular aneurysm repair using the St George's Vascular Institute score. AB - BACKGROUND: Identifying patients at risk for aneurysm rupture and sac expansion after open and endovascular abdominal aortic aneurysm (AAA) repair (EVAR) may help to attenuate this risk by intensifying follow-up and early detection of problems. The goal of this study was to validate the St George's Vascular Institute (SGVI) score to identify patients at risk for a secondary intervention after elective aneurysm repair. METHODS: A post hoc on-treatment analysis of a randomized trial comparing open AAA repair and EVAR was performed. In this multicenter trial, 351 patients were randomly assigned to undergo open AAA repair or EVAR. Information on survival and reinterventions was available for all patients at 5 years postoperatively, for 79% at 6 years, and for 53% at 7 years. Open repair was completed in 173 patients and EVAR in 171, based on an on treatment analysis. Because 17 patients had incomplete anatomic data, 327 patients (157 open repair and 170 EVAR) were available for analysis. During 6 years of follow-up, 78 patients underwent at least one reintervention. The SGVI score, which is calculated from preoperative AAA morphology using aneurysm and iliac diameter, predictively dichotomized patients into groups at high-risk or low-risk for a secondary intervention. The observed freedom from reintervention was compared between groups at predicted high-risk and predicted low-risk. RESULTS: The 20 patients in the high-risk group were indeed at higher risk for a secondary intervention compared with the 307 patients predicted to be at low risk (hazard ratio [HR], 3.82; 95% confidence interval [CI], 2.05-7.11; P < .001). Discrimination between high-risk and low-risk groups was valid for EVAR (HR, 4.06; 95% CI, 1.93-8.51; P < .001) and for open repair (HR, 3.41; 95% CI, 1.02 11.4; P = .033). CONCLUSIONS: The SGVI score appears to be a useful tool to predict reintervention risk in patients after open repair and EVAR. PMID- 27005593 TI - Obesogenic environment - intervention opportunities. AB - OBJECTIVES: To evaluate environmental obesogenic-related factors, such as physical activity in neighborhoods and schools, nutritional behavior, and intervention programs. SOURCES: Critical analysis of literature with personal point of view from infant obesity experts and political advisors for public intervention. DATA SYNTHESIS: Although obesity is a public health problem affecting several age groups, it is among children and adolescents that it plays a more important role, due to treatment complexity, high likelihood of persistence into adulthood, and association with other non-transmissible diseases while still in early age. Environment is a main component of the genesis and outcomes in the near future or long term. Modification of intake with high density food, meal skipping, and high intake of saturated fat, sugar, and salt, associated to high levels of sedentarism are main causes of obesity. CONCLUSION: Intervention opportunities are related to modifications in political, environmental, and individual settings. School and physical activities in the educational environment are intertwined with nutrition intervention in continuous education. A critical review of some different scenarios in Latin American countries is presented. PMID- 27005594 TI - Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma. AB - Fatty acid amide hydrolase (FAAH) inhibitors are addressed for promising anxiolytics, but human studies on genetically reduced FAAH activity, stress and affective phenotypes are scarce. We investigated the effect of a functional polymorphism of FAAH (FAAH C385A or rs324420; low FAAH activity and high anandamide concentration are associated with the A allele) together with childhood adversity on the anxious and depressive phenotypes in 858 subjects from the general population. Phenotypes were measured by the Zung Self-Rating Depression Scale (ZSDS), the depression and anxiety subscales of the Brief Symptom Inventory (BSI-DEP, BSI-ANX) and the State-Trait Anxiety scales (STAI-S, STAI-T). Childhood Adversity Questionnaire (CHA) was used to assess early life traumas. Frequency of the A allele was greater among subjects with high ZSDS scores compared to the CC genotype. Furthermore, FAAH C385A and the CHA have shown a robust gene-environment interaction, namely, significantly higher anxiety and depression scores were exhibited by individuals carrying the A allele if they had high CHA scores compared to CC carriers. These data provided preliminary evidence that genetically reduced FAAH activity and repetitive stress in the childhood are associated with increased vulnerability for anxiety and depression in later life. Our results together with earlier experimental data suggest that permanently elevated anandamide level together with early life stress may cause a lifelong damage on stress response probably via the downregulation of CB1R during the neurodevelopment in the brain. It may also point to pharmacogenomic consequences, namely ineffectiveness or adverse effects of FAAH inhibitors in this subpopulation. PMID- 27005595 TI - Biomarkers for drug development in early psychosis: Current issues and promising directions. AB - A major goal of current research in schizophrenia is to understand the biology underlying onset and early progression and to develop interventions that modify these processes. Biomarkers can play a critical role in identifying disease state, factors contributing to underlying progression, as well as predicting and monitoring response to treatment. Once biomarker-based therapeutics are established, biomarkers can guide treatment selection. It is increasingly clear that a wide range of potential biomarkers should be examined in schizophrenia, given the large number of genetic and environmental factors that have been identified as risk factors. New models for analysis of biomarkers are needed that represent the central nervous system as a highly complex, dynamic, and interactive system. Many tools are available with which to study relevant brain chemistry, but most are indirect measures and represent only a small fraction of the potential etiologic factors contributing to the molecular, structural and functional components of schizophrenia. This review represents the work of the International Society for CNS Clinical Trials and Methodology (ISCTM) Biomarkers Working Group. It discusses advantages and disadvantages of different categories of biomarkers and provides a summary of evidence that biomarkers representing inflammation, oxidative stress, endocannabinoids, glucocorticoid, and biogenic amines systems are dysregulated and potentially interactive in early phase schizophrenia. As has been recently demonstrated in several neurodevelopmental and neurodegenerative disorders, a multi-modal, longitudinal strategy involving a diverse array of biomarkers and new approaches to statistical modeling are needed to improve early interventions based on the fuller understanding. PMID- 27005596 TI - Does comorbid chronic pain affect posttraumatic stress disorder diagnosis and treatment? Outcomes of posttraumatic stress disorder screening in Department of Veterans Affairs primary care. AB - Because posttraumatic stress disorder (PTSD) is both prevalent and underrecognized, routine primary care-based screening for PTSD has been implemented across the Veterans Health Administration. PTSD is frequently complicated by the presence of comorbid chronic pain, and patients with both conditions have increased symptom severity and poorer prognosis. Our objective was to determine whether the presence of pain affects diagnosis and treatment of PTSD among Department of Veterans Affairs (VA) patients who have a positive PTSD screening test. This retrospective cohort study used clinical and administrative data from six Midwestern VA medical centers. We identified 4,244 VA primary care patients with a positive PTSD screen and compared outcomes for those with and without a coexisting pain diagnosis. Outcomes were three clinically appropriate responses to positive PTSD screening: (1) mental health visit, (2) PTSD diagnosis, and (3) new selective serotonin reuptake inhibitor (SSRI) prescription. We found that patients with coexisting pain had a lower rate of mental health visits than those without pain (hazard ratio: 0.889, 95% confidence interval: 0.821-0.962). There were no significant differences in the rate of PTSD diagnosis or new SSRI prescription between patients with and without coexisting pain. PMID- 27005597 TI - Rhubarb Anthraquinones Protect Rats against Mercuric Chloride (HgCl2)-Induced Acute Renal Failure. AB - Mercury (Hg) causes severe nephrotoxicity in subjects with excess exposure. This work attempted to identify whether a natural medicine--rhubarb--has protective effects against mercuric chloride (HgCl2)-induced acute renal failure (ARF), and which of its components contributed most to the treatment. Total rhubarb extract (TR) were separated to the total anthraquinones (TA), the total tannins (TT) and remaining component extract (RC). Each extract was orally pre-administered to rats for five successive days followed by HgCl2 injection to induce kidney injury. Subsequently, renal histopathology and biochemical examinations were performed in vitro to evaluate the protective effects. Pharmacological studies showed that TR and TA, but not TT or RC manifested significant protection activity against HgCl2-induced ARF. There were also significant declines of serum creatine, urea nitrogen values and increases of total protein albumin levels in TR and TA treated groups compared to HgCl2 alone (p < 0.05). At last, the major components in TA extract were further identified as anthraquinones by liquid chromatography coupled mass spectroscopy. This study thus provides observational evidences that rhubarb could ameliorate HgCl2-induced ARF and its anthraquinones in particular are the effective components responsible for this activity in rhubarb extract. PMID- 27005598 TI - Synthesis of New Bis(3-hydroxy-4-pyridinone) Ligands as Chelating Agents for Uranyl Complexation. AB - Five new bis(3-hydroxy-4-pyridinone) tetradentate chelators were synthesized in this study. The structures of these tetradentate chelators were characterized by 1H-NMR, (13)C-NMR, FT-IR, UV-vis, and mass spectral analyses. The binding abilities of these tetradentate chelators for uranyl ion at pH 7.4 were also determined by UV spectrophotometry in aqueous media. Results showed that the efficiencies of these chelating agents are dependent on the linker length. Ligand 4b is the best chelator and suitable for further studies. PMID- 27005599 TI - Differential Response of Two Human Breast Cancer Cell Lines to the Phenolic Extract from Flaxseed Oil. AB - Many studies have evidenced that the phenolic components from flaxseed (FS) oil have potential health benefits. The effect of the phenolic extract from FS oil has been evaluated on two human breast cancer cell lines, MCF7 and MDA-MB231, and on the human non-cancerous breast cell line, MCF10A, by SRB assay, cellular death, cell cycle, cell signaling, lipid peroxidation and expression of some key genes. We have evidenced that the extract shows anti-proliferative activity on MCF7 cells by inducing cellular apoptosis, increase of the percentage of cells in G0/G1 phase and of lipid peroxidation, activation of the H2AX signaling pathway, and upregulation of a six gene signature. On the other hand, on the MDA-MB2131 cells we verified only an anti-proliferative activity, a weak lipid peroxidation, the activation of the PI3K signaling pathway and an up-regulation of four genes. Overall these data suggest that the extract has both cytotoxic and pro-oxidant effects only on MCF7 cells, and can act as a metabolic probe, inducing differences in the gene expression. For this purpose, we have performed an interactomic analysis, highlighting the existing associations. From this approach, we show that the phenotypic difference between the two cell lines can be explained through their differential response to the phenolic extract. PMID- 27005600 TI - Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile. AB - Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969) was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant. PMID- 27005601 TI - Porphyrins as Catalysts in Scalable Organic Reactions. AB - Catalysis is a topic of continuous interest since it was discovered in chemistry centuries ago. Aiming at the advance of reactions for efficient processes, a number of approaches have been developed over the last 180 years, and more recently, porphyrins occupy an important role in this field. Porphyrins and metalloporphyrins are fascinating compounds which are involved in a number of synthetic transformations of great interest for industry and academy. The aim of this review is to cover the most recent progress in reactions catalysed by porphyrins in scalable procedures, thus presenting the state of the art in reactions of epoxidation, sulfoxidation, oxidation of alcohols to carbonyl compounds and C-H functionalization. In addition, the use of porphyrins as photocatalysts in continuous flow processes is covered. PMID- 27005602 TI - Pharmacokinetic and Metabolic Characteristics of Herb-Derived Khellactone Derivatives, A Class of Anti-HIV and Anti-Hypertensive: A Review. AB - A vast number of structural modifications have been performed for khellactone derivatives (KDs) that have been widely concerned owing to their diverse biological properties, including anti-hypertension, anti-HIV, reversing P glycoprotein (P-gp) mediated multidrug resistance, and anti-inflammation effects, to find the most active entity. However, extensive metabolism of KDs results in poor oral bioavailability, thus hindering the clinical trial performance of those components. The primary metabolic pathways have been revealed as hydrolysis, oxidation, acyl migration, and glucuronidation, while carboxylesterases and cytochrome P450 3A (CPY3A), as well as UDP-glucuronosyltransferases (UGTs) primarily mediate these metabolic pathways. Attention was mainly paid to the pharmacological features, therapeutic mechanisms and structure-activity relationships of KDs in previous reviews, whereas their pharmacokinetic and metabolic characteristics have seldom been discussed. In the present review, KDs' metabolism and their pharmacokinetic properties are summarized. In addition, the structure-metabolism relationships of KDs and the potential drug-drug interactions (DDIs) induced by KDs were also extensively discussed. The polarity, the acyl groups substituted at C-3' and C-4' positions, the configuration of C-3' and C-4', and the moieties substituted at C-3 and C-4 positions play the determinant roles for the metabolic profiles of KDs. Contributions from CYP3A4, UGT1A1, P-gp, and multidrug resistance-associated protein 2 have been disclosed to be primary for the potential DDIs. The review is expected to provide meaningful information and helpful guidelines for the further development of KDs. PMID- 27005603 TI - Structure, Solubility and Stability of Orbifloxacin Crystal Forms: Hemihydrate versus Anhydrate. AB - Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures. PMID- 27005604 TI - Hydrazonoyl Chlorides as Precursors for Synthesis of Novel Bis-Pyrrole Derivatives. AB - A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular docking of the bis-pyrrole derivatives was performed by the Molecular Operating Environment (MOE) program. PMID- 27005605 TI - Porphyrin Macrocycle Modification: Pyrrole Ring-Contracted or -Expanded Porphyrinoids. AB - In recent years, several synthetic strategies aiming at the peripheral functionalization of porphyrins were developed. Particularly interesting are those involving the modification of beta-pyrrolic positions leading to pyrrole modified porphyrins containing four-, five-, six- or seven-membered heterocycles. Azeteoporphyrins, porpholactones and morpholinoporphyrins are representative examples of such porphyrinoids. These porphyrin derivatives have recently gained an increasing interest due to their potential application in PDT, as multimodal imaging contrast agents, NIR-absorbing dyes, optical sensors for oxygen, cyanide, hypochlorite and pH, and in catalysis. PMID- 27005606 TI - Isolation, Purification and Quantification of Ginsenoside F5 and F3 Isomeric Compounds from Crude Extracts of Flower Buds of Panax ginseng. AB - In this paper, the isolation, purification and quantification of ginsenoside F5 and F3 isomeric compounds from crude extracts of flower buds of Panax ginseng (CEFBPG) was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC) for the first time. The satisfied separation at analytical scale was achieved using a Zorbax Eclipse XDB C-18 column with a ternary mobile phase of acetonitrile-water-phosphoric acid (28:71:1) at a flow rate of 1.0 mL/min within 40 min. UV detection was set at 203 nm. Ginsenoside F5 and F3 was 4.21 mg and 5.13 mg in 1 g flower buds of P. ginseng (FBPG), respectively. The preparation of ginsenoside F5 and F3 at semi-preparative scale was performed by using a Daisogel C-18 column and gradient elution system of acetonitrile-water (32:68 -> 28:72) at a flow rate of 10 mL/min with a sample load of 20-30 mg, and yielded ginsenosides in purity of more than 96%. Their structures were characterized by NMR and high resolution electrospray ionization mass spectrometry (HRESIMS). All the method validations showed acceptable limits. The results indicate a new source to obtain ginsenoside F5 and F3, and show that the method developed here appears to be reliable for simultaneously preparing them from CEFBPG. PMID- 27005607 TI - Liquid Chromatography with Tandem Mass Spectrometry: A Sensitive Method for the Determination of Dehydrodiisoeugenol in Rat Cerebral Nuclei. AB - A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is developed for the quantification of dehydrodiisoeugenol (DDIE) in rat cerebral nuclei after single intravenous administration. DDIE and daidzein (internal standard) were separated on a DiamonsilTM ODS C18 column with methanol-water containing 0.1% formic acid (81:19, v/v) as a mobile phase. Detection of DDIE was performed on a positive electrospray ionization source using a triple quadrupole mass spectrometer. DDIE and daidzein were monitored at m/z 327.2->188.0 and m/z 255.0->199.2, respectively, in multiple reaction monitoring mode. This method enabled quantification of DDIE in various brain areas, including, cortex, hippocampus, striatum, hypothalamus, cerebellum and brainstem, with high specificity, precision, accuracy, and recovery. The data herein demonstrate that our new LC-MS/MS method is highly sensitive and suitable for monitoring cerebral nuclei distribution of DDIE. PMID- 27005608 TI - Synthesis and Selective Cytotoxic Activities on Rhabdomyosarcoma and Noncancerous Cells of Some Heterocyclic Chalcones. AB - Chemically diverse heterocyclic chalcones were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against rhabdomyosarcoma (RMS) and noncancerous cell line (LLC-PK1). The influence of heteroaryl patterns on rings A and B was studied. Heterocycle functionalities on both rings, such as phenothiazine, thiophene, furan and pyridine were evaluated. Notably, the introduction of three methoxy groups at positions 3, 4, 5 on ring B appears to be critical for cytotoxicity. The best compound, with potent and selective cytotoxicity (IC50 = 12.51 MUM in comparison with the value 10.84 MUM of paclitaxel), contains a phenothiazine moiety on ring A and a thiophene heterocycle on ring B. Most of the potential compounds only show weak cytoxicity on the noncancerous cell line LLC-PK1. PMID- 27005609 TI - A Computational Study of the Mechanism of Succinimide Formation in the Asn-His Sequence: Intramolecular Catalysis by the His Side Chain. AB - The rates of deamidation reactions of asparagine (Asn) residues which occur spontaneously and nonenzymatically in peptides and proteins via the succinimide intermediate are known to be strongly dependent on the nature of the following residue on the carboxyl side (Xxx). The formation of the succinimide intermediate is by far the fastest when Xxx is glycine (Gly), the smallest amino acid residue, while extremely slow when Xxx is bulky such as isoleucine (Ile) and valine (Val). In this respect, it is very interesting to note that the succinimide formation is definitely accelerated when Xxx is histidine (His) despite its large size. In this paper, we computationally show that, in an Asn-His sequence, the His side chain imidazole group (in the neutral Nepsilon-protonated form) can specifically catalyze the formation of the tetrahedral intermediate in the succinimide formation by mediating a proton transfer. The calculations were performed for Ace Asn-His-Nme (Ace = acetyl, Nme = methylamino) as a model compound by the density functional theory with the B3LYP functional and the 6-31+G(d,p) basis set. We also show that the tetrahedral intermediate, once protonated at the NH2 group, easily releases an ammonia molecule to give the succinimide species. PMID- 27005610 TI - New Cerebroside and Nucleoside Derivatives from a Red Sea Strain of the Marine Cyanobacterium Moorea producens. AB - In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2'-deoxyuridine (2) and 3-phenylethyl-2'-deoxyuridine (3), along with the previously reported compounds thymidine (4) and 2,3-dihydroxypropyl heptacosanoate (5). The structures of the compounds were determined by different spectroscopic studies (UV, IR, 1D, 2D NMR, and HRESIMS), as well as comparison with the literature data. Compounds 1-5 showed variable cytotoxic activity against three cancer cell lines. PMID- 27005611 TI - Molecular Cloning and Expression Analysis of IgD in Nile Tilapia (Oreochromis niloticus) in Response to Streptococcus agalactiae Stimulus. AB - IgD is considered to be a recently-evolved Ig and a puzzling molecule, being previously found in all vertebrate taxa, except for birds. Although IgD likely plays an important role in vertebrate immune responses, the function of IgD in Nile tilapia (Oreochromis niloticus) is virtually unknown. In the present study, a membrane form of IgD (mIgD) heavy chains were cloned from the GIFT strain of Nile tilapia (designated On-mIgD). The On-mIgD heavy chain's cDNA is composed of 3347 bp with a 31 bp of 5'-UTR, 3015 bp open reading frame (ORF) and 301 bp 3' UTR, encoding a polypeptide of 1004 amino acids (GenBank accession no: KF530821). Phylogenetic analysis revealed that On-mIgD heavy chains showed the highest similarity to Siniperca chuatsi. Quantitative real-time PCR (qRT-PCR) analysis showed that On-mIgD expression occurred predominately in head kidney, thymus, spleen, and kidney. After Streptococcus agalactiae infection, transcripts of On mIgD increased and reached its peak at 48 h in the head kidney and thymus, and 72 h in the spleen, respectively. Taken together, these results collectively indicated that IgD could possibly have a key role to play in the immune response when bacterial infections in Nile tilapia. PMID- 27005612 TI - Molecular Characterization and Expression Analyses of the Complement Component C8alpha, C8beta and C9 Genes in Yellow Catfish (Pelteobagrus fulvidraco) after the Aeromonas hydrophila Challenge. AB - The complement components C8alpha, C8beta and C9 have important roles in the innate immune system against invading microorganisms. Partial cDNA sequences of the Pf_C8alpha, Pf_C8beta and Pf_C9 genes (Pf: abbreviation of Pelteobagrus fulvidraco) were cloned from yellow catfish. The Pf_C8alpha, Pf_C8beta and Pf_C9 genes showed the greatest amino acid similarity to C8alpha (54%) and C8beta (62%) of zebrafish and to C9 (52%) of grass carp, respectively. Ontogenetic expression analyses using real-time quantitative PCR suggested that the three genes may play crucial roles during embryonic and early larval development. The mRNA expressions of the three genes were all at the highest levels in liver tissue, and at lower or much lower levels in 16 other tissues, demonstrating that the liver is the primary site for the protein synthesis of Pf_C8alpha, Pf_C8beta and Pf_C9. Injection of Aeromonas hydrophila led to up-regulation of the three genes in the spleen, head kidney, kidney, liver and blood tissues, indicating that the three genes may contribute to the host's defense against invading pathogenic microbes. An increased understanding of the functions of the Pf_C8alpha, Pf_C8beta and Pf_C9 genes in the innate immunity of yellow catfish will help enhance production of this valuable freshwater species. PMID- 27005613 TI - Hypertension and Dementia: Epidemiological and Experimental Evidence Revealing a Detrimental Relationship. AB - Hypertension and dementia represent two major public health challenges worldwide, notably in the elderly population. Although these two conditions have classically been recognized as two distinct diseases, mounting epidemiological, clinical and experimental evidence suggest that hypertension and dementia are strictly intertwined. Here, we briefly report how hypertension profoundly affects brain homeostasis, both at the structural and functional level. Chronic high blood pressure modifies the cerebral vasculature, increasing the risk of Abeta clearance impairment. The latter, excluding genetic etiologies, is considered one of the main causes of Abeta deposition in the brain. Studies have shown that hypertension induces cerebral arterial stiffening and microvascular dysfunction, thus contributing to dementia pathophysiology. This review examines the existing and the updated literature which has attempted to explain and clarify the relationship between hypertension and dementia at the pathophysiological level. PMID- 27005614 TI - Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta "Gold Standard" Leaves. AB - Leaf color change of variegated leaves from chimera species is regulated by fine tuned molecular mechanisms. Hosta "Gold Standard" is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta "Gold Standard", as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta "Gold Standard". For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves. PMID- 27005616 TI - MicroRNAs in Osteoclastogenesis and Function: Potential Therapeutic Targets for Osteoporosis. AB - Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Over the past two decades, much progress has been made to target osteoclasts. The existing therapeutic drugs include bisphosphonates, hormone replacement therapy, selective estrogen receptor modulators, calcitonin and receptor activator of nuclear factor NF-kappaB ligand (RANKL) inhibitor (denosumab), etc. Among them, bisphosphonates are most widely used due to their low price and high efficiency in reducing the risk of fracture. However, bisphosphonates still have their limitations, such as the gastrointestinal side effects, osteonecrosis of the jaw, and atypical subtrochanteric fracture. Based on the current situation, research for new drugs to regulate bone resorption remains relevant. MicroRNAs (miRNAs) are a new group of small, noncoding RNAs of 19-25 nucleotides, which negatively regulate gene expression after transcription. Recent studies discovered miRNAs play a considerable function in bone remodeling by regulating osteoblast and osteoclast differentiation and function. An increasing number of miRNAs have been identified to participate in osteoclast formation, differentiation, apoptosis, and resorption. miRNAs show great promise to serve as biomarkers and potential therapeutic targets for osteoporosis. In this review, we will summarize our current understanding of how miRNAs regulate osteoclastogenesis and function. We will further discuss the approach to develop drugs for osteoporosis based on these miRNA networks. PMID- 27005615 TI - Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target. AB - It is well established that the brain can be prepared to resist or tolerate ischemic stroke injury, and mitochondrion is a major target for this tolerance. The preparation of ischemic stroke tolerance can be achieved by three major approaches: ischemic conditioning, hypoxic conditioning and chemical conditioning. In each conditioning approach, there are often two strategies that can be used to achieve the conditioning effects, namely preconditioning (Pre-C) and postconditioning (Post-C). In this review, we focus on chemical conditioning of mitochondrial proteins as targets for neuroprotection against ischemic stroke injury. Mitochondrial targets covered include complexes I, II, IV, the ATP sensitive potassium channel (mitoKATP), adenine dinucleotide translocase (ANT) and the mitochondrial permeability transition pore (mPTP). While numerous mitochondrial proteins have not been evaluated in the context of chemical conditioning and ischemic stroke tolerance, the paradigms and approaches reviewed in this article should provide general guidelines on testing those mitochondrial components that have not been investigated. A deep understanding of mitochondria as the target of chemical conditioning for ischemic stroke tolerance should provide valuable insights into strategies for fighting ischemic stroke, a leading cause of death in the world. PMID- 27005618 TI - Transcriptome and Gene Ontology (GO) Enrichment Analysis Reveals Genes Involved in Biotin Metabolism That Affect L-Lysine Production in Corynebacterium glutamicum. AB - Corynebacterium glutamicum is widely used for amino acid production. In the present study, 543 genes showed a significant change in their mRNA expression levels in L-lysine-producing C. glutamicum ATCC21300 than that in the wild-type C. glutamicum ATCC13032. Among these 543 differentially expressed genes (DEGs), 28 genes were up- or downregulated. In addition, 454 DEGs were functionally enriched and categorized based on BLAST sequence homologies and gene ontology (GO) annotations using the Blast2GO software. Interestingly, NCgl0071 (bioB, encoding biotin synthase) was expressed at levels ~20-fold higher in the L-lysine producing ATCC21300 strain than that in the wild-type ATCC13032 strain. Five other genes involved in biotin metabolism or transport--NCgl2515 (bioA, encoding adenosylmethionine-8-amino-7-oxononanoate aminotransferase), NCgl2516 (bioD, encoding dithiobiotin synthetase), NCgl1883, NCgl1884, and NCgl1885--were also expressed at significantly higher levels in the L-lysine-producing ATCC21300 strain than that in the wild-type ATCC13032 strain, which we determined using both next-generation RNA sequencing and quantitative real-time PCR analysis. When we disrupted the bioB gene in C. glutamicum ATCC21300, L-lysine production decreased by approximately 76%, and the three genes involved in biotin transport (NCgl1883, NCgl1884, and NCgl1885) were significantly downregulated. These results will be helpful to improve our understanding of C. glutamicum for industrial amino acid production. PMID- 27005617 TI - A Protease Inhibitor with Induction Therapy with Natural Interferon-beta in Patients with HCV Genotype 1b Infection. AB - The restoration of innate immune responses has potential as a novel therapeutic strategy for chronic hepatitis C (CHC). We compared the efficacy and safety of induction therapy (IT) with natural interferon-beta (n-IFN-beta) followed by pegylated-IFN-alpha/ribavirin (PR) alone (group A, n = 30) and IT with a protease inhibitor (PI) (simeprevir or vaniprevir)/PR (group B, n = 13) in CHC patients with genotype 1b and high viral loads. During IT with nIFN-beta, virologic response rates in group A and group B were 10% and 8% (p = 0.6792) at week 4, 30% and 16% (p = 0.6989) at week 12 and 47% and 20% (p = 0.0887) at week 24 respectively. During and after the treatment with PR alone or PI/PR, virologic response rates in groups A and B were 50% and 82% (p = 0.01535) at week 4, 53% and 91% (p = 0.006745) at week 8, 57% and 91% (p = 0.001126) at week 12, 57% and 100% (p < 0.001845) at the end of the treatment and 57% and 80% (p < 0.005166) after treatment cessation. IT with PI/PR linked to the restoration of innate immune response was tolerated well, overcame virological breakthrough, enhanced early virologic responses, and resulted in a sustained virologic response in difficult-to-treat CHC patients. IT with PI/PR is beneficial for treating difficult-to-treat CHC patients. PMID- 27005619 TI - Effects of Beverages on Alcohol Metabolism: Potential Health Benefits and Harmful Impacts. AB - Nonalcoholic beverages are usually consumed accompanying alcoholic drinks, and their effects on alcohol metabolism are unclear in vivo. In this study, the effects of 20 nonalcoholic beverages on alcohol metabolism and liver injury caused by alcohol were evaluated in mice. Kunming mice were orally fed with alcohol (52%, v/v) and beverages. The concentrations of ethanol and acetaldehyde in blood as well as the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver were assessed to indicate alcohol metabolism. The levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) in serum as well as the levels of malonaldehyde (MDA) and superoxide dismutase (SOD) in liver were measured to reflect the alcohol-induced liver injury. The results showed that the treatment of soda water, green tea and honey chrysanthemum tea could accelerate ethanol metabolism and prevent liver injuries caused by alcohol when companied with excessive alcohol drinking. They might be potential dietary supplements for the alleviation of harmful effects from excessive alcohol consumption. On the contrary, some beverages such as fresh orange juice and red bull are not advised to drink when companied with alcohol consumption due to their adverse effects on ethanol induced liver injury. PMID- 27005621 TI - Identification of Human UDP-Glucuronosyltransferase 1A4 as the Major Isozyme Responsible for the Glucuronidation of 20(S)-Protopanaxadiol in Human Liver Microsomes. AB - 20(S)-protopanaxadiol (PPD), one of the representative aglycones of ginsenosides, has a broad spectrum of pharmacological activities. Although phase I metabolism has been investigated extensively, information regarding phase II metabolism of this compound remains to be elucidated. Here, a glucuronidated metabolite of PPD in human liver microsomes (HLMs) and rat liver microsomes (RLMs) was unambiguously identified as PPD-3-O-beta-D-glucuronide by nuclear magnetic resonance spectroscopy and high resolution mass spectrometry. The chemical inhibition and recombinant human UDP-Glucuronosyltransferase (UGT) isoforms assay showed that the PPD glucuronidation was mainly catalyzed by UGT1A4 in HLM, whereas UGT1A3 showed weak catalytic activity. In conclusion, PPD-3-O-beta-D glucuronide was first identified as the principal glucuronidation metabolite of PPD in HLMs, which was catalyzed by UGT1A4. PMID- 27005623 TI - Measuring Surface Pressure on Rotating Compressor Blades Using Pressure Sensitive Paint. AB - Pressure sensitive paint (PSP) was used to measure pressure on the blades of a radial compressor with a 51 mm inlet diameter rotating at speeds up to 50 krpm using the so called lifetime method. A diode laser with a scanning-mirror system was used to illuminate the paint and the luminescent lifetime was registered using a photo multiplier. With the described technique the surface-pressure fields were acquired for eight points in the compressor map, useful for general understanding of the flow field and for CFD validation. The PSP was of so called fast type, which makes it possible to observe pressure variations with frequencies up to several kHz. Through frequency spectrum analysis we were able to detect the pulsating flow frequency when the compressor was driven to surge. PMID- 27005620 TI - Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection--Liver: The "Musketeer" in the Spotlight. AB - The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a "vicious circle", eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved. PMID- 27005624 TI - Protocol to Exploit Waiting Resources for UASNs. AB - The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN) is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols. PMID- 27005622 TI - Spinal Cord T-Cell Infiltration in the Rat Spared Nerve Injury Model: A Time Course Study. AB - The immune system is involved in the development of neuropathic pain. In particular, the infiltration of T-lymphocytes into the spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used the spared nerve injury (SNI) model of neuropathic pain in Sprague Dawley adult male rats to assess proliferation, and/or protein/gene expression levels for microglia (Iba1), T-lymphocytes (CD2) and cytotoxic T lymphocytes (CD8). In the dorsal horn ipsilateral to SNI, Iba1 and BrdU stainings revealed microglial reactivity and proliferation, respectively, with different durations. Iba1 expression peaked at D4 and D7 at the mRNA and protein level, respectively, and was long-lasting. Proliferation occurred almost exclusively in Iba1 positive cells and peaked at D2. Gene expression observation by RT-qPCR array suggested that T-lymphocytes attracting chemokines were upregulated after SNI in rat spinal cord but only a few CD2/CD8 positive cells were found. A pronounced infiltration of CD2/CD8 positive T-cells was seen in the spinal cord injury (SCI) model used as a positive control for lymphocyte infiltration. Under these experimental conditions, we show early and long-lasting microglia reactivity in the spinal cord after SNI, but no lymphocyte infiltration was found. PMID- 27005625 TI - Estimating Clothing Thermal Insulation Using an Infrared Camera. AB - In this paper, a novel algorithm for estimating clothing insulation is proposed to assess thermal comfort, based on the non-contact and real-time measurements of the face and clothing temperatures by an infrared camera. The proposed method can accurately measure the clothing insulation of various garments under different clothing fit and sitting postures. The proposed estimation method is investigated to be effective to measure its clothing insulation significantly in different seasonal clothing conditions using a paired t-test in 99% confidence interval. Temperatures simulated with the proposed estimated insulation value show closer to the values of actual temperature than those with individual clothing insulation values. Upper clothing's temperature is more accurate within 3% error and lower clothing's temperature is more accurate by 3.7%~6.2% error in indoor working scenarios. The proposed algorithm can reflect the effect of air layer which makes insulation different in the calculation to estimate clothing insulation using the temperature of the face and clothing. In future, the proposed method is expected to be applied to evaluate the customized passenger comfort effectively. PMID- 27005626 TI - Performance Analysis of Motion-Sensor Behavior for User Authentication on Smartphones. AB - The growing trend of using smartphones as personal computing platforms to access and store private information has stressed the demand for secure and usable authentication mechanisms. This paper investigates the feasibility and applicability of using motion-sensor behavior data for user authentication on smartphones. For each sample of the passcode, sensory data from motion sensors are analyzed to extract descriptive and intensive features for accurate and fine grained characterization of users' passcode-input actions. One-class learning methods are applied to the feature space for performing user authentication. Analyses are conducted using data from 48 participants with 129,621 passcode samples across various operational scenarios and different types of smartphones. Extensive experiments are included to examine the efficacy of the proposed approach, which achieves a false-rejection rate of 6.85% and a false-acceptance rate of 5.01%. Additional experiments on usability with respect to passcode length, sensitivity with respect to training sample size, scalability with respect to number of users, and flexibility with respect to screen size were provided to further explore the effectiveness and practicability. The results suggest that sensory data could provide useful authentication information, and this level of performance approaches sufficiency for two-factor authentication on smartphones. Our dataset is publicly available to facilitate future research. PMID- 27005627 TI - The Design and Optimization of a Highly Sensitive and Overload-Resistant Piezoresistive Pressure Sensor. AB - A piezoresistive pressure sensor with a beam-membrane-dual-island structure is developed for micro-pressure monitoring in the field of aviation, which requires great sensitivity and overload resistance capacity. The design, fabrication, and test of the sensor are presented in this paper. By analyzing the stress distribution of sensitive elements using the finite element method, a novel structure incorporating sensitive beams with a traditional bossed diaphragm is built up. The proposed structure proved to be advantageous in terms of high sensitivity and high overload resistance compared with the conventional bossed diaphragm and flat diaphragm structures. Curve fittings of surface stress and deflection based on ANSYS simulation results are performed to establish the sensor equations. Fabricated on an n-type single crystal silicon wafer, the sensor chips are wire-bonded to a printed circuit board (PCB) and packaged for experiments. The static and dynamic characteristics are tested and discussed. Experimental results show that the sensor has a sensitivity as high as 17.339 MUV/V/Pa in the range of 500 Pa at room temperature, and a high overload resistance of 200 times overpressure. Due to the excellent performance, the sensor can be applied in measuring micro-pressure lower than 500 Pa. PMID- 27005628 TI - Standalone GPS L1 C/A Receiver for Lunar Missions. AB - Global Navigation Satellite Systems (GNSSs) were originally introduced to provide positioning and timing services for terrestrial Earth users. However, space users increasingly rely on GNSS for spacecraft navigation and other science applications at several different altitudes from the Earth surface, in Low Earth Orbit (LEO), Medium Earth Orbit (MEO), Geostationary Earth Orbit (GEO), and feasibility studies have proved that GNSS signals can even be tracked at Moon altitude. Despite this, space remains a challenging operational environment, particularly on the way from the Earth to the Moon, characterized by weaker signals with wider gain variability, larger dynamic ranges resulting in higher Doppler and Doppler rates and critically low satellite signal availability. Following our previous studies, this paper describes the proof of concept "WeakHEO" receiver; a GPS L1 C/A receiver we developed in our laboratory specifically for lunar missions. The paper also assesses the performance of the receiver in two representative portions of an Earth Moon Transfer Orbit (MTO). The receiver was connected to our GNSS Spirent simulator in order to collect real time hardware-in-the-loop observations, and then processed by the navigation module. This demonstrates the feasibility, using current technology, of effectively exploiting GNSS signals for navigation in a MTO. PMID- 27005629 TI - Laser Feedback Interferometry as a Tool for Analysis of Granular Materials at Terahertz Frequencies: Towards Imaging and Identification of Plastic Explosives. AB - We propose a self-consistent method for the analysis of granular materials at terahertz (THz) frequencies using a quantum cascade laser. The method is designed for signals acquired from a laser feedback interferometer, and applied to non contact reflection-mode sensing. Our technique is demonstrated using three plastic explosives, achieving good agreement with reference measurements obtained by THz time-domain spectroscopy in transmission geometry. The technique described in this study is readily scalable: replacing a single laser with a small laser array, with individual lasers operating at different frequencies will enable unambiguous identification of select materials. This paves the way towards non contact, reflection-mode analysis and identification of granular materials at THz frequencies using quantum cascade lasers. PMID- 27005630 TI - A New, Scalable and Low Cost Multi-Channel Monitoring System for Polymer Electrolyte Fuel Cells. AB - In this work a new, scalable and low cost multi-channel monitoring system for Polymer Electrolyte Fuel Cells (PEFCs) has been designed, constructed and experimentally validated. This developed monitoring system performs non-intrusive voltage measurement of each individual cell of a PEFC stack and it is scalable, in the sense that it is capable to carry out measurements in stacks from 1 to 120 cells (from watts to kilowatts). The developed system comprises two main subsystems: hardware devoted to data acquisition (DAQ) and software devoted to real-time monitoring. The DAQ subsystem is based on the low-cost open-source platform Arduino and the real-time monitoring subsystem has been developed using the high-level graphical language NI LabVIEW. Such integration can be considered a novelty in scientific literature for PEFC monitoring systems. An original amplifying and multiplexing board has been designed to increase the Arduino input port availability. Data storage and real-time monitoring have been performed with an easy-to-use interface. Graphical and numerical visualization allows a continuous tracking of cell voltage. Scalability, flexibility, easy-to-use, versatility and low cost are the main features of the proposed approach. The system is described and experimental results are presented. These results demonstrate its suitability to monitor the voltage in a PEFC at cell level. PMID- 27005631 TI - Automatic Lumen Detection on Longitudinal Ultrasound B-Mode Images of the Carotid Using Phase Symmetry. AB - This article describes a method that improves the performance of previous approaches for the automatic detection of the common carotid artery (CCA) lumen centerline on longitudinal B-mode ultrasound images. We propose to detect several lumen centerline candidates using local symmetry analysis based on local phase information of dark structures at an appropriate scale. These candidates are analyzed with selection mechanisms that use symmetry, contrast or intensity features in combination with position-based heuristics. Several experimental results are provided to evaluate the robustness and performance of the proposed method in comparison with previous approaches. These results lead to the conclusion that our proposal is robust to noise, lumen artifacts, contrast variations and that is able to deal with the presence of CCA-like structures, significantly improving the performance of our previous approach, from 87.5% +/- 0.7% of correct detections to 98.3% +/- 0.3% in a set of 200 images. PMID- 27005632 TI - Fast Contour-Tracing Algorithm Based on a Pixel-Following Method for Image Sensors. AB - Contour pixels distinguish objects from the background. Tracing and extracting contour pixels are widely used for smart/wearable image sensor devices, because these are simple and useful for detecting objects. In this paper, we present a novel contour-tracing algorithm for fast and accurate contour following. The proposed algorithm classifies the type of contour pixel, based on its local pattern. Then, it traces the next contour using the previous pixel's type. Therefore, it can classify the type of contour pixels as a straight line, inner corner, outer corner and inner-outer corner, and it can extract pixels of a specific contour type. Moreover, it can trace contour pixels rapidly because it can determine the local minimal path using the contour case. In addition, the proposed algorithm is capable of the compressing data of contour pixels using the representative points and inner-outer corner points, and it can accurately restore the contour image from the data. To compare the performance of the proposed algorithm to that of conventional techniques, we measure their processing time and accuracy. In the experimental results, the proposed algorithm shows better performance compared to the others. Furthermore, it can provide the compressed data of contour pixels and restore them accurately, including the inner-outer corner, which cannot be restored using conventional algorithms. PMID- 27005633 TI - Antimicrobials from Cnidarians. A New Perspective for Anti-Infective Therapy? AB - The ability of microbes to counter the scientific and therapeutic advancements achieved during the second half of the twentieth century to provide effective disease treatments is currently a significant challenge for researchers in biology and medicine. The discovery of antibiotics, and the subsequent development of synthetic antimicrobial compounds, altered our therapeutic approach towards infectious diseases, and improved the quality and length of life for humans and other organisms. The current alarming rise in cases of antibiotic resistance has forced biomedical researchers to explore new ways to recognize and/or produce new antimicrobials or to find other approaches for existing therapeutics. Aquatic organisms are known to be a source of compounds having the potential to play a role in fighting the battle against pathogenic microbes. In this connection, cnidarians occupy a pre-eminent role. Over the past few decades several studies have explored the antimicrobial/antibiotic properties of cnidarian extracts with the aim of isolating compounds possessing useful therapeutic features. This paper aims to review the existing data on this subject, taking into account the possible utilization of identified compounds. PMID- 27005634 TI - Bioprospecting of Marine Macrophytes Using MS-Based Lipidomics as a New Approach. AB - The marine environment supports a remarkable diversity of organisms which are a potential source of natural products with biological activities. These organisms include a wide variety of marine plants (from micro- to macrophytes), which have been used in the food and pharmaceutical industry. However, the biochemistry and biological activities of many of these macrophytes (namely macroalgae and halophytes, including seagrasses) are still far from being fully explored. Most popular bioactive components include polysaccharides, peptides, phenolics and fatty acids (FAs). Polar lipids (glycolipids, phospholipids and betaine lipids) are emerging as novel value-added bioactive phytochemicals, rich in n-3 FA, with high nutritional value and health beneficial effects for the prevention of chronic diseases. Polar lipids account various combinations of polar groups, fatty acyl chains and backbone structures. The polar lipidome of macrophytes is remarkably diverse, and its screening represents a significant analytical challenge. Modern research platforms, particularly mass spectrometry (MS)-based lipidomic approaches, have been recently used to address this challenge and are here reviewed. The application of lipidomics to address lipid composition of marine macrophytes will contribute to the stimulation of further research on this group and foster the exploration of novel applications. PMID- 27005635 TI - Comparison of Protein Phosphatase Inhibition Assay with LC-MS/MS for Diagnosis of Microcystin Toxicosis in Veterinary Cases. AB - Microcystins are acute hepatotoxins of increasing global concern in drinking and recreational waters and are a major health risk to humans and animals. Produced by cyanobacteria, microcystins inhibit serine/threonine protein phosphatase 1 (PP1). A cost-effective PP1 assay using p-nitrophenyl phosphate was developed to quickly assess water and rumen content samples. Significant inhibition was determined via a linear model, which compared increasing volumes of sample to the log-transformed ratio of the exposed rate over the control rate of PP1 activity. To test the usefulness of this model in diagnostic case investigations, samples from two veterinary cases were tested. In August 2013 fifteen cattle died around two ponds in Kentucky. While one pond and three tested rumen contents had significant PP1 inhibition and detectable levels of microcystin-LR, the other pond did not. In August 2013, a dog became fatally ill after swimming in Clear Lake, California. Lake water samples collected one and four weeks after the dog presented with clinical signs inhibited PP1 activity. Subsequent analysis using liquid chromatography-mass spectrometry (LC-MS/MS) detected microcystin congeners -LR, -LA, -RR and -LF but not -YR. These diagnostic investigations illustrate the advantages of using functional assays in combination with LC-MS/MS. PMID- 27005636 TI - Heterotrophic Production of Omega-3 Long-Chain Polyunsaturated Fatty Acids by Trophically Converted Marine Diatom Phaeodactylum tricornutum. AB - We have created via metabolic engineering a heterotrophic strain of Phaeodactylum tricornutum that accumulates enhanced levels of the high value omega-3 long chain polyunsaturated fatty acid (LC-PUFAs) docosahexaenoic acid (DHA). This was achieved by generation of transgenic strains in which the Delta5-elongase from Ostreococcus tauri was co-expressed with a glucose transporter from the moss Physcomitrella patens. This double transformant has the capacity to grow in the dark in liquid medium supplemented with glucose and accumulate substantial levels of omega-3 LC-PUFAs. The effects of glucose concentrations on growth and LC-PUFA production of wild type and transformed strains cultivated in the light and dark were studied. The highest omega-3 LC-PUFAs accumulation was observed in cultures grown under mixotrophic conditions in the presence of 1% glucose (up to 32.2% of total fatty acids, TFA). Both DHA and EPA are detected at high levels in the neutral lipids of transgenic cells grown under phototrophic conditions, averaging 36.5% and 23.6% of TFA, respectively. This study demonstrates the potential for P. tricornutum to be developed as a viable commercial strain for both EPA and DHA production under mixo- and heterotrophic conditions. PMID- 27005637 TI - Antimicrobial Action of Compounds from Marine Seaweed. AB - Seaweed produces metabolites aiding in the protection against different environmental stresses. These compounds show antiviral, antiprotozoal, antifungal, and antibacterial properties. Macroalgae can be cultured in high volumes and would represent an attractive source of potential compounds useful for unconventional drugs able to control new diseases or multiresistant strains of pathogenic microorganisms. The substances isolated from green, brown and red algae showing potent antimicrobial activity belong to polysaccharides, fatty acids, phlorotannins, pigments, lectins, alkaloids, terpenoids and halogenated compounds. This review presents the major compounds found in macroalga showing antimicrobial activities and their most promising applications. PMID- 27005638 TI - Nigrodiquinone A, a Hydroanthraquinone Dimer Containing a Rare C-9-C-7' Linkage from a Zoanthid-Derived Nigrospora sp. Fungus. AB - One new hydroanthraquinone dimer with a rare C-9-C-7' linkage, nigrodiquinone A (1), and four known anthraquinone monomers 2-5, were isolated from a fungus Nigrospora sp. obtained from the zoanthid Palythoa haddoni collected in the South China Sea. The structure of 1 was established through extensive NMR spectroscopy, and the absolute configuration was elucidated by comparing computed electronic circular dichroism (ECD) and optical rotations (OR) with experimental results. All the compounds were evaluated for antiviral activity, and 1 was also evaluated for antibacterial activity. Compound 4 displayed mild antiviral activity against coxsackie virus (Cox-B3) with the IC50 value of 93.7 MUM, and 5 showed an IC50 value of 74.0 MUM against respiratory syncytial virus (RSV). PMID- 27005639 TI - Study on the Effects of Irrigation with Reclaimed Water on the Content and Distribution of Heavy Metals in Soil. AB - Reclaimed water is an important resource for irrigation, and exploration in making full use of it is an important way to alleviate water shortage. This paper analyzes the effects of irrigation with reclaimed water through field trials on the content and distribution of heavy metals in both tomatoes and the soil. By exploring the effects of reclaimed water after secondary treatment on the content and distribution characteristics of heavy metals in tomatoes and the heavy metal balance in the soil-crop system under different conditions, the study shows that there are no significant differences in the heavy metal content when the quantity of reclaimed water for irrigation varies. Reclaimed water for short-term irrigation does not cause pollution to either the soil environment or the crops. Nor will it cause the accumulation of heavy metals, and the index for the heavy metal content is far below the critical value of the national standard, which indicates that the vegetables irrigated with reclaimed water during their growth turn out to be free of pollutants. The heavy metals brought into the soil by reclaimed water are less than that taken away by the crops. The input and output quantities have only small effects on the heavy metal balance in the soil. This paper provides a reference for the evaluation and safety control of irrigation with reclaimed water. PMID- 27005640 TI - Superior Effects of Antiretroviral Treatment among Men Who have Sex with Men Compared to Other HIV At-Risk Populations in a Large Cohort Study in Hunan, China. AB - This study assesses association between CD4 level at initiation of antiretroviral treatment (ART) on subsequent treatment outcomes and mortality among people infected with HIV via various routes in Hunan province, China. Over a period of 10 years, a total of 7333 HIV-positive patients, including 553 (7.5%) MSM, 5484 (74.8%) heterosexuals, 1164 (15.9%) injection drug users (IDU) and 132 (1.8%) former plasma donors (FPD), were recruited. MSM substantially demonstrated higher initial CD4 cell level (242, IQR 167-298) than other populations (Heterosexuals: 144 IQR 40-242, IDU: 134 IQR 38-224, FPD: 86 IQR 36-181). During subsequent long term follow up, the median CD4 level in all participants increased significantly from 151 cells/mm3 (IQR 43-246) to 265 cells/mm3 (IQR 162-380), whereas CD4 level in MSM remained at a high level between 242 and 361 cells/mm3. Consistently, both cumulative immunological and virological failure rates (10.4% and 26.4% in 48 months, respectively) were the lowest in MSM compared with other population groups. Survival analysis indicated that initial CD4 counts <= 200 cells/mm3 (AHR = 3.14; CI, 2.43-4.06) significantly contributed to HIV-related mortality during treatment. Timely diagnosis and treatment of HIV patients are vital for improving CD4 level and health outcomes. PMID- 27005641 TI - The Risk Factors of Child Lead Poisoning in China: A Meta-Analysis. AB - BACKGROUND: To investigate the risk factors of child lead poisoning in China. METHODS: A document retrieval was performed using MeSH (Medical subject heading terms) and key words. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the studies, and the pooled odd ratios with a 95% confidence interval were used to identify the risk factors. We employed Review Manager 5.2 and Stata 10.0 to analyze the data. Heterogeneity was assessed by both the Chi-square and I2 tests, and publication bias was evaluated using a funnel plot and Egger's test. RESULTS: Thirty-four articles reporting 13,587 lead-poisoned children met the inclusion criteria. Unhealthy lifestyle and behaviors, environmental pollution around the home and potential for parents' occupational exposure to lead were risk factors of child lead poisoning in the pooled analyses. Our assessments yielded no severe publication biases. CONCLUSIONS: Seventeen risk factors are associated with child lead poisoning, which can be used to identify high-risk children. Health education and promotion campaigns should be designed in order to minimize or prevent child lead poisoning in China. PMID- 27005642 TI - Slaughterhouses Fungal Burden Assessment: A Contribution for the Pursuit of a Better Assessment Strategy. AB - In slaughterhouses, the biological risk is present not only from the direct or indirect contact with animal matter, but also from the exposure to bioaerosols. Fungal contamination was already reported from the floors and walls of slaughterhouses. This study intends to assess fungal contamination by cultural and molecular methods in poultry, swine/bovine and large animal slaughterhouses. Air samples were collected through an impaction method, while surface samples were collected by the swabbing method and subjected to further macro- and micro scopic observations. In addition, we collected air samples using the impinger method in order to perform real-time quantitative PCR (qPCR) amplification of genes from specific fungal species, namely A. flavus, A. fumigatus and A. ochraceus complexes. Poultry and swine/bovine slaughterhouses presented each two sampling sites that surpass the guideline of 150 CFU/m3. Scopulariopsis candida was the most frequently isolated (59.5%) in poultry slaughterhouse air; Cladosporium sp. (45.7%) in the swine/bovine slaughterhouse; and Penicillium sp. (80.8%) in the large animal slaughterhouse. Molecular tools successfully amplified DNA from the A. fumigatus complex in six sampling sites where the presence of this fungal species was not identified by conventional methods. This study besides suggesting the indicators that are representative of harmful fungal contamination, also indicates a strategy as a protocol to ensure a proper characterization of fungal occupational exposure. PMID- 27005643 TI - Immunotoxicity Monitoring in a Population Exposed to Polychlorinated Biphenyls. AB - The relationship between polychlorinated biphenyl (PCB) burden and several indicators of immune function was investigated as part of the HELPcB (Health Effects in High-Level Exposure to PCB) program, offering bio-monitoring to workers, relatives, and neighbors exposed to PCBs by a German transformers and capacitors recycling company. The present retrospective observational study evaluates the correlation of plasma levels of total PCBs, five indicator congeners (28, 101, 138, 153, 180), and seven dioxin-like congeners (105, 114, 118, 156, 157, 167, 189) with several parameters of immune function. The cross sectional study was performed immediately after the end of exposure (258 subjects), and one (218 subjects), and two (177 subjects) years later. At the first time point, measurements showed significant positive correlation between congeners with low to medium chlorination and the relative proportion of CD19 positive B-cells among lymphocytes, as well as a negative correlation of PCB114 with serum IgM, and of PCB 28 with suppressor T-cell and NK-cell numbers. Congeners with a high degree of chlorination, in particular PCB157 and 189, were positively associated with expression of the activation marker CD25 on T-cells in the cohort of the second time point. No associations between PCB levels and IFN-y production by T-cells and killing by NK-cells were found. In conclusion, there were several effects on the cellular composition of adaptive immunity, affecting both T- and B-cells. However, the values were not generally outside the reference ranges for healthy adult individuals and did not indicate overt functional immunodeficiency, even in subjects with the uppermost PCB burden. PMID- 27005645 TI - The Built Environment and Active Travel: Evidence from Nanjing, China. AB - BACKGROUND: An established relationship exists between the built environment and active travel. Nevertheless, the literature examining the impacts of different components of the built environment is limited. In addition, most existing studies are based on data from cities in the U.S. and Western Europe. The situation in Chinese cities remains largely unknown. Based on data from Nanjing, China, this study explicitly examines the influences of two components of the built environment--the neighborhood form and street form--on residents' active travel. METHODS: Binary logistic regression analyses examined the effects of the neighborhood form and street form on subsistence, maintenance and discretionary travel, respectively. For each travel purpose, three models are explored: a model with only socio-demographics, a model with variables of the neighborhood form and a complete model with all variables. RESULTS: The model fit indicator, Nagelkerke's rho2, increased by 0.024 when neighborhood form variables are included and increased by 0.070 when street form variables are taken into account. A similar situation can be found in the models of maintenance activities and discretionary activities. Regarding specific variables, very limited significant impacts of the neighborhood form variables are observed, while almost all of the characteristics of the street form show significant influences on active transport. CONCLUSIONS: In Nanjing, street form factors have a more profound influence on active travel than neighborhood form factors. The focal point of the land use regulations and policy of local governments should shift from the neighborhood form to the street form to maximize the effects of policy interventions. PMID- 27005644 TI - Pathological Internet Use and Risk-Behaviors among European Adolescents. AB - Risk-behaviors are a major contributor to the leading causes of morbidity among adolescents and young people; however, their association with pathological Internet use (PIU) is relatively unexplored, particularly within the European context. The main objective of this study is to investigate the association between risk-behaviors and PIU in European adolescents. This cross-sectional study was conducted within the framework of the FP7 European Union project: Saving and Empowering Young Lives in Europe (SEYLE). Data on adolescents were collected from randomized schools within study sites across eleven European countries. PIU was measured using Young's Diagnostic Questionnaire (YDQ). Risk behaviors were assessed using questions procured from the Global School-Based Student Health Survey (GSHS). A total of 11,931 adolescents were included in the analyses: 43.4% male and 56.6% female (M/F: 5179/6752), with a mean age of 14.89 +/- 0.87 years. Adolescents reporting poor sleeping habits and risk-taking actions showed the strongest associations with PIU, followed by tobacco use, poor nutrition and physical inactivity. Among adolescents in the PIU group, 89.9% were characterized as having multiple risk-behaviors. The significant association observed between PIU and risk-behaviors, combined with a high rate of co occurrence, underlines the importance of considering PIU when screening, treating or preventing high-risk behaviors among adolescents. PMID- 27005646 TI - Mortality during a Large-Scale Heat Wave by Place, Demographic Group, Internal and External Causes of Death, and Building Climate Zone. AB - Mortality increases during periods of elevated heat. Identification of vulnerable subgroups by demographics, causes of death, and geographic regions, including deaths occurring at home, is needed to inform public health prevention efforts. We calculated mortality relative risks (RRs) and excess deaths associated with a large-scale California heat wave in 2006, comparing deaths during the heat wave with reference days. For total (all-place) and at-home mortality, we examined risks by demographic factors, internal and external causes of death, and building climate zones. During the heat wave, 582 excess deaths occurred, a 5% increase over expected (RR = 1.05, 95% confidence interval (CI) 1.03-1.08). Sixty-six percent of excess deaths were at home (RR = 1.12, CI 1.07-1.16). Total mortality risk was higher among those aged 35-44 years than >= 65, and among Hispanics than whites. Deaths from external causes increased more sharply (RR = 1.18, CI 1.10 1.27) than from internal causes (RR = 1.04, CI 1.02-1.07). Geographically, risk varied by building climate zone; the highest risks of at-home death occurred in the northernmost coastal zone (RR = 1.58, CI 1.01-2.48) and the southernmost zone of California's Central Valley (RR = 1.43, CI 1.21-1.68). Heat wave mortality risk varied across subpopulations, and some patterns of vulnerability differed from those previously identified. Public health efforts should also address at home mortality, non-elderly adults, external causes, and at-risk geographic regions. PMID- 27005647 TI - Meta-Analysis of Cardiac Mortality in Three Cohorts of Carbon Black Production Workers. AB - Epidemiological studies have demonstrated associations between airborne environmental particle exposure and cardiac disease and mortality; however, few have examined such effects from poorly soluble particles of low toxicity such as manufactured carbon black (CB) particles in the work place. We combined standardised mortality ratio (SMR) and Cox proportional hazards results from cohort studies of US, UK and German CB production workers. Under a common protocol, we analysed mortality from all causes, heart disease (HD), ischemic heart disease (IHD) and acute myocardial infarction (AMI). Fixed and random effects (RE) meta-regression models were fit for employment duration, and for overall cumulative and lugged quantitative CB exposure estimates. Full cohort meta-SMRs (RE) were 1.01 (95% confidence interval (CI) 0.79-1.29) for HD; 1.02 (95% CI 0.80-1.30) for IHD, and 1.08 (95% CI 0.74-1.59) for AMI mortality. For all three outcomes, meta-SMRs were heterogeneous, increased with time since first and time since last exposure, and peaked after 25-29 or 10-14 years, respectively. Meta-Cox coefficients showed no association with lugged duration of exposure. A small but imprecise increased AMI mortality risk was suggested for cumulative exposure (RE-hazards ratio (HR) = 1.10 per 100 mg/m3-years; 95% CI 0.92-1.31), but not for lugged exposures. Our results do not demonstrate that airborne CB exposure increases all-cause or cardiac disease mortality. PMID- 27005648 TI - Biodegradation of Phenol by Bacteria Strain Acinetobacter Calcoaceticus PA Isolated from Phenolic Wastewater. AB - A phenol-degrading bacterium strain PA was successfully isolated from the effluent of petrochemical wastewater. Based on its morphological, physiological and biochemical characteristics, the strain PA was characterized as a Gram negative, strictly aerobic, nonmotile and short rod-shaped bacterium that utilizes phenol as a sole carbon and energy source. 16S rDNA sequence analysis revealed that this strain is affiliated to Acinetobacter calcoaceticus in the group of Gammaproteobacteria. The strain was efficient in removing 91.6% of the initial 800 mg ? L(-1) phenol within 48 h, and had a tolerance of phenol concentration as high as 1700 mg ? L(-1). These results indicated that A. calcoaceticus possesses a promising potential in treating phenolic wastewater. PMID- 27005649 TI - Concurrent Heroin Use and Correlates among Methadone Maintenance Treatment Clients: A 12-Month Follow-up Study in Guangdong Province, China. AB - OBJECTIVE: To assess concurrent heroin use and correlates among Methadone Maintenance Treatment (MMT) clients in Guangdong Province, China. METHOD: Demographic and drug use data were collected with a structured questionnaire, and MMT information was obtained from the MMT clinic registration system in Guangdong. Human immunodeficiency virus (HIV-) and hepatitis C virus (HCV) infected status and urine morphine results were obtained from laboratory tests. Logistic regressions were employed to investigate the factors associated with concurrent heroin use. RESULTS: Among the 6848 participants, 75% continued using heroin more than once during the first 12 months after treatment initiation. Concurrent heroin use was associated with inharmonious family relationship (OR (odds ratio) = 1.49, 95% CI (confidence intervals): 1.24-1.78), HIV positivity (OR = 1.25, 95% CI: 1.01-1.55), having multiple sex partners (OR = 1.34, 95% CI: 1.07-1.69), having ever taken intravenous drugs (OR = 0.81, 95% CI: 0.69-0.95), higher maintenance dose (OR = 1.13, 95% CI: 1.01-1.28) and poorer MMT attendance (OR < 20% = 1.32, 95% CI: 1.13-1.53; OR 20%- = 1.33, 95% CI: 1.14-1.54; OR 50%- = 1.69, 95% CI: 1.44-2.00). Among those who used heroin concurrently, the same factors, and additionally being older (OR 35- = 1.26, 95% CI: 1.11-1.43; OR >= 45 = 1.63, 95% CI: 1.30-2.05) and female (OR = 1.60, 95% CI: 1.28-2.00), contribute to a greater frequency of heroin use. CONCLUSIONS: Concurrent heroin use was prevalent among MMT participants in Guangdong, underscoring the urgent needs for tailored interventions and health education programs for this population. PMID- 27005650 TI - Effects of Sachet Water Consumption on Exposure to Microbe-Contaminated Drinking Water: Household Survey Evidence from Ghana. AB - There remain few nationally representative studies of drinking water quality at the point of consumption in developing countries. This study aimed to examine factors associated with E. coli contamination in Ghana. It drew on a nationally representative household survey, the 2012-2013 Living Standards Survey 6, which incorporated a novel water quality module. E. coli contamination in 3096 point-of consumption samples was examined using multinomial regression. Surface water use was the strongest risk factor for high E. coli contamination (relative risk ratio (RRR) = 32.3, p < 0.001), whilst packaged (sachet or bottled) water use had the greatest protective effect (RRR = 0.06, p < 0.001), compared to water piped to premises. E. coli contamination followed plausible patterns with digit preference (tendency to report values ending in zero) in bacteria counts. The analysis suggests packaged drinking water use provides some protection against point-of consumption E. coli contamination and may therefore benefit public health. It also suggests viable water quality data can be collected alongside household surveys, but field protocols require further revision. PMID- 27005651 TI - Global Evidence on the Association between POS Advertising Bans and Youth Smoking Participation. AB - BACKGROUND: Point-of-sale (POS) tobacco advertising has been linked to youth smoking susceptibility and experimental smoking. However, there is limited evidence of the association between POS advertising bans and youth smoking participation. This study aims to examine how such bans are associated with current smoking, daily smoking, and regular smoking (>= 1 cigarettes per day) participation among youth. METHODS: one to two waves (primarily one wave) of the Global Youth Tobacco Survey were conducted in 130 countries between 2007 and 2011. These surveys were linked to the WHO "MPOWER" data using country and year identifiers to analyze the association between POS advertising bans (a dichotomous measure of the existence of such bans) and smoking participation in the past month. Weighted logistic regressions were employed to analyze this association while controlling for age, gender, parents' smoking status, 6 MPOWER policy scores, and GDP per capita. RESULTS AND CONCLUSIONS: We find that in countries with POS advertising bans, current smoking (OR = 0.73, p <= 0.1), daily smoking (OR = 0.70, p <= 0.1), and regular smoking (OR = 0.75, p <= 0.05) participation in the past month is significantly lower, suggesting that POS promotion bans can potentially reduce youth smoking. This study provides evidence to support the implementation of POS promotion regulations by the US FDA and implementation of the WHO FCTC guidelines regarding restrictions on tobacco POS promotion. PMID- 27005652 TI - Compensation for Adolescents' School Mental Load by Physical Activity on Weekend Days. AB - INTRODUCTION AND OBJECTIVE: Increasing mental load and inadequate stress management significantly affect the efficiency, success and safety of the educational/working process in adolescents. The objective of this study is to determine the extent that adolescents compensate for their school mental load by physical activity (PA) on weekend days and, thus, to contribute to the objective measurement of mental load in natural working conditions. METHODS: A cross sectional study was conducted between September 2013 and April 2014. A set of different methods was employed-self-administered questionnaire (IPAQ-long questionnaire), objective measurements-pedometers, and accelerometers (ActiTrainers). They was distributed to 548 students from 17 high schools. Participants' mental load was assessed based on the difference between PA intensity and/or physical inactivity and heart rate range. RESULTS: The participants with the highest mental load during school lessons do not compensate for this load by PA on weekend days. CONCLUSIONS: Adolescents need to be encouraged to be aware of their subjective mental load and to intentionally compensate for this load by PA on weekend days. It is necessary to support the process of adopting habits by sufficient physical literacy of students, as well as teachers, and by changes in the school program. PMID- 27005653 TI - Fungi from a Groundwater-Fed Drinking Water Supply System in Brazil. AB - Filamentous fungi in drinking water distribution systems are known to (a) block water pipes; (b) cause organoleptic biodeterioration; (c) act as pathogens or allergens and (d) cause mycotoxin contamination. Yeasts might also cause problems. This study describes the occurrence of several fungal species in a water distribution system supplied by groundwater in Recife-Pernambuco, Brazil. Water samples were collected from four sampling sites from which fungi were recovered by membrane filtration. The numbers in all sampling sites ranged from 5 to 207 colony forming units (CFU)/100 mL with a mean value of 53 CFU/100 mL. In total, 859 isolates were identified morphologically, with Aspergillus and Penicillium the most representative genera (37% and 25% respectively), followed by Trichoderma and Fusarium (9% each), Curvularia (5%) and finally the species Pestalotiopsis karstenii (2%). Ramichloridium and Leptodontium were isolated and are black yeasts, a group that include emergent pathogens. The drinking water system in Recife may play a role in fungal dissemination, including opportunistic pathogens. PMID- 27005654 TI - Adolescent Overweight and Obesity: Links to Socioeconomic Status and Fruit and Vegetable Intakes. AB - Whether adolescent overweight/obesity is linked to socioeconomic status (SES) and fruit and vegetable (F/V) intakes has not been confirmed. We aimed to determine whether there is an association between SES and adolescent overweight/obesity and to test the mediating effect of F/V intakes. This cross-sectional study included the data of 63,111 adolescents extracted from the 2013 Korea Youth Risk Behavior Web-based Survey. Overweight/obesity was defined as a body mass index >= 85th percentile, while F/V intakes were categorized as high (recommended levels: >= 1 fruit serving and >= 3 vegetable servings per day) versus low. Among girls, low SES (beta = 0.50, p < 0.001) and F/V intakes (beta = -0.17, p = 0.038) were both significantly associated with overweight/obesity; the former association was significantly mediated by F/V intakes (Sobel test: z = 2.00, p = 0.046). Among boys, neither SES nor F/V intakes was significantly associated with overweight/obesity. Adolescent overweight/obesity was significantly linked to low SES and F/V intakes among girls only; low SES indirectly increased the risk of overweight/obesity via low F/V intakes. Therefore, promoting F/V intakes for socially disadvantaged girls should be prioritized as a population-based strategy for preventing adolescent overweight/obesity in South Korea. PMID- 27005655 TI - Recycling Endosomes and Viral Infection. AB - Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition. PMID- 27005656 TI - Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission. AB - The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4+ T-cells, and to a lesser extent, CD8+ T-cells, dendritic cells, and monocytes. Efficient infection of CD4+ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4+ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation. PMID- 27005657 TI - Vitamin Status among Breastfed Infants in Bhaktapur, Nepal. AB - Vitamin deficiencies are known to be common among infants residing in low- and middle-income countries but relatively few studies have assessed several biochemical parameters simultaneously. The objective of the study was to describe the status of vitamins (A, D, E, B6, B12 and folate) in breastfed infants. We measured the plasma concentrations of trans retinol, 25 hydroxy vitamin D, alpha tocopherol, pyridoxal 5'-phosphate, cobalamin, folate, methylmalonic acid, homocysteine, hemoglobin and C-reactive protein from 467 randomly selected infants. One in five (22%) was deficient in at least one vitamin. Mean (SD) plasma folate concentration was 73 (35) nmol/L, and no infant in the sample was folate deficient. Vitamin B6 deficiency and vitamin B12 deficiency was found in 22% and 17% of the infants, respectively. Elevated plasma methylmalonic acid or total homocysteine concentration was found in 82% and 62% of infants, respectively. Fifteen percent of infants were vitamin A deficient and 65% were marginally deficient in vitamin A. Fewer than 5% of infants had low plasma vitamin D concentration or vitamin E concentration (alpha-tocopherol <9.3 umol/L). Our results illustrate the importance of continued supplementation campaigns and support the expansion of food fortification and dietary diversification programs that target children and women in Nepal. PMID- 27005658 TI - Clinical Evaluation of Effects of Chronic Resveratrol Supplementation on Cerebrovascular Function, Cognition, Mood, Physical Function and General Well Being in Postmenopausal Women-Rationale and Study Design. AB - BACKGROUND: This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis. METHOD: Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound. CONCLUSION: This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations. PMID- 27005659 TI - Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region. AB - Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID- 27005660 TI - Carbohydrate Mouth Rinse Maintains Muscle Electromyographic Activity and Increases Time to Exhaustion during Moderate but not High-Intensity Cycling Exercise. AB - The aim was to investigate the influence of a carbohydrate (CHO) mouth rinse on the vastus lateralis (VL) and rectus femoris (RF) electromyographic activity (EMG) and time to exhaustion (TE) during moderate (MIE) and high-intensity cycling exercise (HIE). Thirteen participants cycled at 80% of their respiratory compensation point and at 110% of their peak power output to the point of exhaustion. Before the trials and every 15 min during MIE, participants rinsed with the CHO or Placebo (PLA) solutions. The root mean square was calculated. CHO had no effect on the TE during HIE (CHO: 177.3 +/- 42.2 s; PLA: 163.0 +/- 26.7 s, p = 0.10), but the TE was increased during MIE (CHO: 76.6 +/- 19.7 min; PLA: 65.4 +/- 15.2 min; p = 0.01). The EMG activity in the VL was higher than PLA at 30 min (CHO: 10.5% +/- 2.6%; PLA: 7.7% +/- 3.3%; p = 0.01) and before exhaustion (CHO: 10.3% +/- 2.5%; PLA: 8.0% +/- 2.9%; p = 0.01) with CHO rinsing. There was no CHO effect on the EMG activity of RF during MIE or for VL and RF during HIE. CHO mouth rinse maintains EMG activity and enhances performance for MIE but not for HIE. PMID- 27005661 TI - Health-Care Costs, Glycemic Control and Nutritional Status in Malnourished Older Diabetics Treated with a Hypercaloric Diabetes-Specific Enteral Nutritional Formula. AB - Diabetes-specific formulas are an effective alternative for providing nutrients and maintaining glycemic control. This study assesses the effect of treatment with an oral enteral nutrition with a hypercaloric diabetes-specific formula (HDSF) for one year, on health-care resources use, health-care costs, glucose control and nutritional status, in 93 type-2 diabetes mellitus (T2DM) malnourished patients. Changes in health-care resources use and health-care costs were collected the year before and during the year of intervention. Glucose status and nutritional laboratory parameters were analyzed at baseline and one year after the administration of HDSF. The administration of HDSF was significantly associated with a reduced use of health-care resources, fewer hospital admissions (54.7%; p < 0.001), days spent at hospital (64.1%; p < 0.001) and emergency visits (57.7%; p < 0.001). Health-care costs were reduced by 65.6% (p < 0.001) during the intervention. Glycemic control (short- and long-term) and the need of pharmacological treatment did not change, while some nutritional parameters were improved at one year (albumin: +10.6%, p < 0.001; hemoglobin: +6.4%, p = 0.026). In conclusion, using HDSF in malnourished older type-2 diabetic patients may allow increasing energy intake while maintaining glucose control and improving nutritional parameters. The use of health-care resources and costs were significantly reduced during the nutritional intervention. PMID- 27005663 TI - Antioxidant Capacities of Hot Water Extracts and Endopolysaccharides of Selected Chinese Medicinal Fruits. AB - Fruits are a rich source of antioxidants and traditional Chinese fruits have been studied for their chemopreventive and chemotherapeutic properties against cancers and other diseases. The total phenol and flavonoid contents of eleven Chinese fruits extracts were determined. Total phenolic and flavonoid contents were estimated by both the Folin-Ciocalteau and aluminium chloride methods. The antioxidant activities were evaluated by four assays: a biological assay using Saccharomyces cerevisiae, DPPH radical scavenging activity, chelating ability for ferrous ions and ferric reducing antioxidant power (FRAP). The phenols and flavonoids contents of the hot water extracts were in the range of 17.7 to 94.7 mg/g and 12.3 to 295.4 mg/g, whereas the endopolysaccharides lie in the range of 4.5 to 77.4 mg/g and 22.7 to 230.0 mg/g. Significant amounts of phenols and flavonoids were present in the majority of the fruit extracts and showed strong antioxidant activities. The antioxidant properties of the fruit extracts of Crataegus pinnatifida, Illicium verum, Ligustrum lucidum, Momordica grosvenori and Psoralea corylifolia as determined by the DPPH and FRAP methods, were significant compared to other fruit extracts. In the present study, we found that significant amounts of phenolic and flavonoid compounds were present in these fruit extracts and may contribute to in vitro antioxidant activities. PMID- 27005662 TI - Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes. AB - Cholesterol is an essential structural component of cellular membranes in eukaryotes. Cholesterol in the exofacial leaflet of the plasma membrane is thought to form membrane nanodomains with sphingolipids and specific proteins. Additionally, cholesterol is found in the intracellular membranes of endosomes and has crucial functions in membrane trafficking. Furthermore, cellular cholesterol homeostasis and regulation of de novo synthesis rely on transport via both vesicular and non-vesicular pathways. Thus, the ability to visualize and detect intracellular cholesterol, especially in the plasma membrane, is critical to understanding the complex biology associated with cholesterol and the nanodomains. Perfringolysin O (PFO) theta toxin is one of the toxins secreted by the anaerobic bacteria Clostridium perfringens and this toxin forms pores in the plasma membrane that causes cell lysis. It is well understood that PFO recognizes and binds to cholesterol in the exofacial leaflets of the plasma membrane, and domain 4 of PFO (D4) is sufficient for the binding of cholesterol. Recent studies have taken advantage of this high-affinity cholesterol-binding domain to create a variety of cholesterol biosensors by using a non-toxic PFO or the D4 in isolation. This review highlights the characteristics and usefulness of, and the principal findings related to, these PFO-derived cholesterol biosensors. PMID- 27005664 TI - Hypoxia Induced NF-kappaB. AB - As Nuclear Factor-kappaB (NF-kappaB) is a major transcription factor responding to cellular stress, it is perhaps not surprising that is activated by hypoxia, or decreased oxygen availability. However, how NF-kappaB becomes activated in hypoxia is still not completely understood. Several mechanisms have been proposed and this review will focus on the main findings highlighting the molecules that have been identified in the process of hypoxia induced NF-kappaB. In addition, we will discuss the role of NF-kappaB in the control of the cellular response to hypoxia. PMID- 27005665 TI - Rab GTPases and the Autophagy Pathway: Bacterial Targets for a Suitable Biogenesis and Trafficking of Their Own Vacuoles. AB - Autophagy is an intracellular process that comprises degradation of damaged organelles, protein aggregates and intracellular pathogens, having an important role in controlling the fate of invading microorganisms. Intracellular pathogens are internalized by professional and non-professional phagocytes, localizing in compartments called phagosomes. To degrade the internalized microorganism, the microbial phagosome matures by fusion events with early and late endosomal compartments and lysosomes, a process that is regulated by Rab GTPases. Interestingly, in order to survive and replicate in the phagosome, some pathogens employ different strategies to manipulate vesicular traffic, inhibiting phagolysosomal biogenesis (e.g., Staphylococcus aureus and Mycobacterium tuberculosis) or surviving in acidic compartments and forming replicative vacuoles (e.g., Coxiella burnetti and Legionella pneumophila). The bacteria described in this review often use secretion systems to control the host's response and thus disseminate. To date, eight types of secretion systems (Type I to Type VIII) are known. Some of these systems are used by bacteria to translocate pathogenic proteins into the host cell and regulate replicative vacuole formation, apoptosis, cytokine responses, and autophagy. Herein, we have focused on how bacteria manipulate small Rab GTPases to control many of these processes. The growing knowledge in this field may facilitate the development of new treatments or contribute to the prevention of these types of bacterial infections. PMID- 27005666 TI - Ciprofloxacin-Induced Antibacterial Activity Is Atteneuated by Pretreatment with Antioxidant Agents. AB - Ciprofloxacin works through interfering with replication and transcription of bacterial DNA, which leads to increased oxidative stress, and death of bacterial cells. Drugs with strong antioxidant such as tempol, melatonin and pentoxifylline might interfere with the antibacterial activity of ciprofloxacin. In the current study, the effect of these drugs on the cytotoxicity of ciprofloxacin was investigated against several reference bacteria. Standard bacterial strains included Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin with or without treatment of bacterial cells by tempol, melatonin or pentoxifylline was assessed using the disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All of the tested bacterial strains were sensitive to ciprofloxacin. When treated with tempol, melatonin or pentoxifylline, all bacterial strains showed significantly smaller zones of inhibition and larger MIC values compared ciprofloxacin alone. In correlation, reactive oxygen species (ROS) generation induced by ciprofloxacin antibacterial action was diminished by treatment of bacterial cells with tempol, melatonin or pentoxifylline. In conclusion, results indicate the possible antagonistic properties for agents with antioxidant properties such as tempol, melatonin and pentoxifylline when they are used concurrently with flouroquinolones. This could be related to the ability of these agents to inhibit oxidative stress in bacterial cells. PMID- 27005667 TI - The Management of Horses during Fireworks in New Zealand. AB - Within popular press there has been much coverage of the negative effects associated with firework and horses. The effect of fireworks has been documented in companion animals, yet no studies have investigated the negative effects, or otherwise, of fireworks on horses. This study aims to document horse responses and current management strategies to fireworks via an online survey. Of the total number of horses, 39% (1987/4765) were rated as "anxious", 40% (1816/4765) "very anxious" and only 21% (965/4765) rated as "not anxious" around fireworks. Running (82%, 912/1107) was the most common behaviour reported, with no difference between property type (p > 0.05) or location (p > 0.05). Possibly as a consequence of the high frequency of running, 35% (384/1107) of respondents reported having horses break through fences in response to fireworks and a quarter (26%, 289/1099) reported that their horse(s) had received injuries associated with fireworks. The most common management strategy was moving their horse(s) to a paddock away from the fireworks (77%) and to stable/yard them (55%). However, approximately 30% reported these management strategies to be ineffective. Of the survey participants, 90% (996/1104) were against the sale of fireworks for private use. PMID- 27005668 TI - Kidney Function as a Determinant of HDL and Triglyceride Concentrations in the Australian Population. AB - BACKGROUND: Chronic kidney disease (CKD) is a potent risk factor for cardiovascular disease (CVD). CVD risk increases in a stepwise manner with increasing kidney impairment and is significantly reduced by kidney transplantation, suggesting a causal relationship. Dyslipidemia, a well recognised CVD risk factor, is highly prevalent in CKD. While dyslipidemia is a risk factor for CKD, kidney impairment can also induce a dyslipidemic state that may contribute to the excess burden of CVD in CKD. We utilised a multipronged approach to determine whether a causal relationship exists. MATERIALS AND METHODS: Retrospective case-control analysis of 816 patients admitted to the Royal Hobart Hospital in 2008-2009 with different degrees of kidney impairment and retrospective before-after cohort analysis of 60 patients who received a transplanted kidney between 1999 and 2009. RESULTS: Decreased estimated GFR (eGFR) was independently associated with decreased high density lipoprotein (HDL, p < 0.0001) and increased triglyceride concentrations (p < 0.01) in multivariate analysis. There was no significant relationship between eGFR and low density lipoprotein (LDL) or total cholesterol in multivariate analysis. Kidney transplantation increased HDL (p < 0.0001) and decreased triglyceride (p = 0.007) concentration, whereas there was no significant change in LDL and total cholesterol. These effects were dependent on maintenance of graft function, statin therapy (those who were on) if graft failure occurred then HDL again decreased and triglycerides increased. CONCLUSIONS: Kidney transplantation ameliorated alterations in plasma lipoprotein profile associated with kidney impairment, an effect that was dependent on the maintenance of graft function. These data suggest that kidney function is a determinant of HDL and triglyceride concentrations in patients with CKD. PMID- 27005669 TI - MicroRNA In Lung Cancer: Novel Biomarkers and Potential Tools for Treatment. AB - Lung cancer is the leading cause of cancer death in men and women worldwide. The lack of specific and sensitive tools for early diagnosis as well as still inadequate targeted therapies contribute to poor outcomes. MicroRNAs are small non-coding RNAs, which regulate gene expression post-transcriptionally by translational repression or degradation of target mRNAs. A growing body of evidence suggests various roles of microRNAs including development and progression of lung cancer. In lung cancer, several studies have showed that certain microRNA profiles classified lung cancer subtypes, and that specific microRNA expression signatures distinguished between better-prognosis and worse prognosis lung cancers. Furthermore, microRNAs circulate in body fluids, and therefore may serve as promising biomarkers for early diagnosis of lung cancer as well as for predicting prognosis of patients. In the present review, we briefly summarize microRNAs in the development and progression of lung cancer, focusing on possible applications of microRNAs as novel biomarkers and tools for treatment. PMID- 27005670 TI - Biochemical and Functional Insights into the Integrated Regulation of Innate Immune Cell Responses by Teleost Leukocyte Immune-Type Receptors. AB - Across vertebrates, innate immunity consists of a complex assortment of highly specialized cells capable of unleashing potent effector responses designed to destroy or mitigate foreign pathogens. The execution of various innate cellular behaviors such as phagocytosis, degranulation, or cell-mediated cytotoxicity are functionally indistinguishable when being performed by immune cells isolated from humans or teleost fishes; vertebrates that diverged from one another more than 450 million years ago. This suggests that vital components of the vertebrate innate defense machinery are conserved and investigating such processes in a range of model systems provides an important opportunity to identify fundamental features of vertebrate immunity. One characteristic that is highly conserved across vertebrate systems is that cellular immune responses are dependent on specialized immunoregulatory receptors that sense environmental stimuli and initiate intracellular cascades that can elicit appropriate effector responses. A wide variety of immunoregulatory receptor families have been extensively studied in mammals, and many have been identified as cell- and function-specific regulators of a range of innate responses. Although much less is known in fish, the growing database of genomic information has recently allowed for the identification of several immunoregulatory receptor gene families in teleosts. Many of these putative immunoregulatory receptors have yet to be assigned any specific role(s), and much of what is known has been based solely on structural and/or phylogenetic relationships with mammalian receptor families. As an attempt to address some of these shortcomings, this review will focus on our growing understanding of the functional roles played by specific members of the channel catfish (Ictalurus punctatus) leukocyte immune-type receptors (IpLITRs), which appear to be important regulators of several innate cellular responses via classical as well as unique biochemical signaling networks. PMID- 27005672 TI - Deep brain stimulation and glioma. PMID- 27005671 TI - The Production Processes and Biological Effects of Intravenous Immunoglobulin. AB - Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production. PMID- 27005673 TI - Lumbar spinal canal dimensions measured intraoperatively after decompression are not properly rendered on early postoperative MRI. AB - BACKGROUND: In cases of lumbar spinal stenosis (LSS) treated with surgical decompression, a postoperative magnetic resonance imaging (MRI) is sometimes required. In the experience of the investigators of this study, the obtained decompression observed on early postoperative MRI tends to be disappointing compared to the decompression achieved intraoperatively. This raises the question of whether the early postoperative MRI, performed after lumbar decompression, is a fair representation of the 'real' decompression. This study investigated the correlation between intraoperative and postoperative measurements of the lumbar spinal canal. METHOD: Twenty patients with LSS underwent surgical decompression on a single level. The orthopaedic surgeon performed direct intraoperative measurements of width, length and height of the spinal canal. Preoperative supine MR images and postoperative prone and supine MR images were acquired. Two radiologists (R.B. and M.G.) measured width, length and height of the spinal canal on the preoperative and postoperative MRIs. Intraoperative measurements were compared to measurements on postoperative MRI in prone position (thus reproducing the intraoperative situation) to avoid positioning bias. Preoperative and postoperative measurements on MR images were also compared. In addition to this, postoperative measurements on supine and prone MR images were also compared. RESULTS: Interobserver reliability for MRI measurements by both radiologists was generally excellent (intraclass correlation coefficients >=0.71). The postoperative spinal canal dimensions improved on both prone and supine MRI compared to the preoperative imaging (P < 0.05). Intraoperatively measured dimensions demonstrated a significantly greater height (difference 2.8 +/- 3.3 [R.B.] and 1.9 +/- 3.7 [M.G.]) and greater width (difference 2.1 +/- 3.2 [R.B.] and 2.5 +/- 2.7 [M.G.]) compared to postoperative MRI in the prone position (P < 0.05). Postoperative dural sac height was greater on the supine MRI compared to the prone MRI (P < 0.05). CONCLUSIONS: Surgical decompression of the spinal canal effectively decreases the compression of the dural sac. However, early postoperative MRI after lumbar decompression does not adequately represent the decompression achieved intraoperatively. PMID- 27005674 TI - Two cases of gallbladder metastasis from renal cell carcinoma and review of literature. AB - BACKGROUND: Renal cell carcinoma accounts for 90% of renal neoplasms and metastatic disease is common. One third of newly diagnosed cases will have synchronous metastases at diagnosis and further 25-50 % will develop metachronous disease. CASE PRESENTATION: This study presents two new cases of gallbladder metastasis from renal cell carcinoma (RCC) from our institution and reviews the published literature. The final cohort included 52 evaluable patients. M/F ratio was 2:1 and median age was 62.5 years. Most patients were diagnosed incidentally after follow-up or staging imaging for RCC. Of the patients with available histology, all except one were clear cell type (n = 39) and 92% were polypoid. Thirty-six patients demonstrated metachronous gallbladder metastasis with median disease-free interval (DFI) from nephrectomy of 4 years. The most frequent site of metastasis was the contralateral kidney (46.7%) followed by the pancreas and lung. The median disease-free interval (DFS) after cholecystectomy was 37 months. Three- and five-year OS rates were 74 and 62%, respectively. Age younger than 45 years (p = 0.008) and DFI <24 months (p = 0.049) were associated with decreased OS. CONCLUSIONS: RCC metastasis to the gallbladder is associated with an unusual pattern of concomitant metastasis. Symptoms are not common. Simple cholecystectomy is associated with increased OS and nil local or port site recurrence. Young age and short DFI are associated with decreased OS. PMID- 27005675 TI - Health perceptions of young adults living with recessive limb-girdle muscular dystrophy. AB - AIM: The aim of this study was to describe health perceptions related to sense of coherence among young adults living with recessive limb-girdle muscular dystrophy. BACKGROUND: Limb-girdle muscular dystrophy refers to a group of progressive muscular disorders that may manifest in physical disability. The focus in health care is to optimize health, which requires knowledge about the content of health as described by the individual. DESIGN: A descriptive study design with qualitative and quantitative data were used. METHOD: Interviews were conducted between June 2012-November 2013 with 14 participants aged 20-30 years. The participants also answered the 13-item sense of coherence questionnaire. Qualitative data were analysed with content analysis and related to self-rated sense of coherence. FINDINGS: Health was viewed as intertwined physical and mental well-being. As the disease progressed, well-being was perceived to be influenced not only by physical impairment and mental strain caused by the disease but also by external factors, such as accessibility to support and attitudes in society. Factors perceived to promote health were having a balanced lifestyle, social relations and meaningful daily activities. Self-rated sense of coherence varied. The median score was 56 (range 37-77). Those who scored >=56 described to a greater extent satisfaction regarding support received, daily pursuits and social life compared with those who scored <56. CONCLUSION: Care should be person-centred. Caregivers, with their knowledge, should strive to assess how the person comprehends, manages and finds meaning in daily life. Through dialogue, not only physical, psychological and social needs but also health-promoting solutions can be highlighted. PMID- 27005676 TI - Low 25-hydroxyvitamin D levels are associated with vitiligo: a systematic review and meta-analysis. AB - BACKGROUND: Vitamin D deficiency is associated with a number of autoimmune diseases. We completed a meta-analysis of observational studies to establish whether there was a relationship between hypovitaminosis D and the autoimmune skin disease vitiligo. METHODS: Comprehensive search was applied in the MEDLINE and EMBASE databases from their inception to December 2015. Inclusion criteria were observational studies that assessed 25-hydroxyvitamin D (25(OH)D) levels in adults with vitiligo. The main outcome was the mean difference in serum 25(OH)D level between patients with vitiligo and controls. RESULTS: Our search strategy identified 383 articles; seventeen studies met the criteria for full-length review and seven studies, containing the data of 1200 patients, were included in a random-effects model meta-analysis. The pooled mean difference in serum 25 hydroxyvitamin D concentration between patients with vitiligo and controls was 7.45 ng/ml (95% confidence interval, -12.99 to -1.91, P-value = 0.01). The between-study heterogeneity (I(2) ) was 96%, P = value<0.001. CONCLUSIONS: This meta-analysis identifies a significant relationship between low 25-hydroxyvitamin D levels and vitiligo, but does not prove causation. Our findings emphasize the importance of measuring 25-hydroxyvitamin D levels in patients with vitiligo. Further studies will be needed to establish whether vitamin D supplementation in this population improves the outcome of vitiligo. PMID- 27005677 TI - Structural revisions of small molecules reported to cross-link G-quadruplex DNA in vivo reveal a repetitive assignment error in the literature. AB - Two molecules of mistaken identity are addressed. Uncovering these assignment errors led us to formulate more general guidelines about additional misassignments in cases of published bis-imines derived from 1,2-phenylenediamine and hydroxybenzaldehydes having no substituent in ortho-positions. The main purpose of this article is to highlight this repetitive assignment error in the literature and thus increase the likelihood of correct assignments in future papers. PMID- 27005678 TI - Authors' response to: "Beta-blocker treatment of caffeine-induced tachydysrhythmias". PMID- 27005679 TI - The effects of mood on spontaneous trait inferences about the actor: Evidence from Chinese undergraduates. AB - Prior research has indicated that positive moods increase but negative moods decrease the trait activation of spontaneous trait inferences (STIs). However, it is unknown whether this difference is also present in STIs about the actor. In Study 1, using a false recognition paradigm, we found that Chinese undergraduates made STIs about the actor. In Study 2, we found that the happy Chinese undergraduates were more likely to make STIs about the actor than the sad Chinese undergraduates. These findings showed that Chinese people made STIs about the actor and moods had an influence on their STIs about the actor. PMID- 27005681 TI - The diet of whiting Merlangius merlangus in the western Baltic Sea. AB - The diet of whiting Merlangius merlangus in the western Baltic Sea was investigated and compared to the diet in the southern North Sea. Clupeids were important prey in both areas, but especially in the western Baltic Sea where they constituted up to 90% of the diet of larger individuals. Gobies, brown shrimps and polychaetes were the main prey of juveniles in the western Baltic Sea, while a wider range of species were consumed in the North Sea. The shift to piscivory occurred at smaller sizes in the western Baltic Sea and the fish prey consumed was proportionately larger than in the southern North Sea. Estimates of prey abundance and food intake of M. merlangus are required to evaluate its predatory significance in the western Baltic Sea, but its diet suggests that it could be just as significant a fish predator here as in the southern North Sea. PMID- 27005680 TI - Influence of ankle fracture surgery on glycemic control in patients with diabetes. AB - BACKGROUND: Although ankle fracture surgery can affect glycemic control by either trauma-induced stress or a postoperative decrease in physical activity, there is little evidence on this issue. This study aimed to evaluate the influence of ankle fracture surgery on glycemic control and to assess the risk factors for poor glycemic control after surgery in patients with diabetes. METHODS: We reviewed the medical records of consecutive patients with diabetes who underwent open reduction and internal fixation for the treatment of ankle fracture at our hospital. Patients who underwent blood testing, including fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and cholesterol levels, as part of a routine check-up before surgery and again more than 2 times after surgery were included. Changes in blood test results were adjusted by multiple factors using a linear mixed model with sex, age at time of surgery, body mass index (BMI), and type of ankle fracture as the fixed effects and each subject and timing of blood test as the random effects. RESULTS: Sixty patients were ultimately included in this study. At 1 month postoperatively, mean FBG and cholesterol levels had increased significantly compared with preoperative levels (p = 0.011 and 0.024, respectively). After surgery, FBG levels showed an estimated monthly decrease of 2.2 mg/dL (p = 0.017). Sex, age at time of surgery, and type of ankle fracture did not significantly affect the monthly change in FBG level. FBG returned to the preoperative level at an estimated period of 8.1 months. BMI significantly affected preoperative FBG level (p = 0.015) but not the postoperative change in FBG level (p = 0.500). CONCLUSION: Ankle fracture surgery increased the FBG level at 1 month postoperatively. FBG levels decreased gradually after surgery at an estimated monthly rate of 2.2 mg/dL. Physicians should be aware of the difficulty in postoperative blood glucose control in patients with diabetes, even several months after surgery. PMID- 27005682 TI - Reliability of the quantitative assessment of peripheral blood perfusion by laser speckle contrast analysis in a systemic sclerosis cohort. PMID- 27005683 TI - Molluscan shell colour. AB - The phylum Mollusca is highly speciose, and is the largest phylum in the marine realm. The great majority of molluscs are shelled, including nearly all bivalves, most gastropods and some cephalopods. The fabulous and diverse colours and patterns of molluscan shells are widely recognised and have been appreciated for hundreds of years by collectors and scientists alike. They serve taxonomists as characters that can be used to recognise and distinguish species, however their function for the animal is sometimes less clear and has been the focus of many ecological and evolutionary studies. Despite these studies, almost nothing is known about the evolution of colour in molluscan shells. This review summarises for the first time major findings of disparate studies relevant to the evolution of shell colour in Mollusca and discusses the importance of colour, including the effects of visual and non-visual selection, diet and abiotic factors. I also summarise the evidence for the heritability of shell colour in some taxa and recent efforts to understand the molecular mechanisms underpinning synthesis of shell colours. I describe some of the main shell pigments found in Mollusca (carotenoids, melanin and tetrapyrroles, including porphyrins and bile pigments), and their durability in the fossil record. Finally I suggest that pigments appear to be distributed in a phylogenetically relevant manner and that the synthesis of colour is likely to be energetically costly. PMID- 27005684 TI - Chest radiograph reading and recording system: evaluation in frontline clinicians in Zambia. AB - BACKGROUND: In Zambia the vast majority of chest radiographs (CXR) are read by clinical officers who have limited training and varied interpretation experience, meaning lower inter-rater reliability and limiting the usefulness of CXR as a diagnostic tool. In 2010-11, the Zambian Prison Service and Ministry of Health established TB and HIV screening programs in six prisons; screening included digital radiography for all participants. Using front-line clinicians we evaluated sensitivity, specificity and inter-rater agreement for digital CXR interpretation using the Chest Radiograph Reading and Recording System (CRRS). METHODS: Digital radiographs were selected from HIV-infected and uninfected inmates who participated in a TB and HIV screening program at two Zambian prisons. Two medical officers (MOs) and two clinical officers (COs) independently interpreted all CXRs. We calculated sensitivity and specificity of CXR interpretations compared to culture as the gold standard and evaluated inter rater reliability using percent agreement and kappa coefficients. RESULTS: 571 CXRs were included in analyses. Sensitivity of the interpretation "any abnormality" ranged from 50-70 % depending on the reader and the patients' HIV status. In general, MO's had higher specificities than COs. Kappa coefficients for the ratings of "abnormalities consistent with TB" and "any abnormality" showed good agreement between MOs on HIV-uninfected CXRs and moderate agreement on HIV-infected CXRs whereas the COs demonstrated fair agreement in both categories, regardless of HIV status. CONCLUSIONS: Sensitivity, specificity and inter-rater agreement varied substantially between readers with different experience and training, however the medical officers who underwent formal CRRS training had more consistent interpretations. PMID- 27005685 TI - Gastric fundal heterotopic pancreas mimicking a gastrointestinal stromal tumour (GIST): a case report and a brief review. AB - BACKGROUND: Heterotopic pancreas is a rare congenital condition characterised by pancreatic tissue lacking vascular or anatomic communication with the normal pancreas. Most cases of ectopic pancreas are asymptomatic. The preoperative diagnosis of this condition is difficult. CASE PRESENTATION: A 50-year-old woman presented with dyspeptic symptoms of 4 years duration. Contrast enhanced CT (computed tomography) scan of abdomen suggested a gastrointestinal stromal tumour in the fundus of the stomach. The patient underwent laparoscopy assisted resection and subsequent histology revealed ectopic pancreatic tissue. CONCLUSION: Although heterotopic pancreas is a rare lesion diagnosed on histology, it should be considered in the differential diagnosis of gastric mass lesions and in patients presenting with vague upper gastrointestinal symptoms. PMID- 27005686 TI - Association study of polymorphism in the serotonin transporter gene promoter, methylation profiles, and expression in patients with major depressive disorder. AB - The serotonin transporter (5HTT) may be associated with the pathogenesis of major depressive disorder (MDD). The 5HTT-linked polymorphic region (5HTTLPR) genotype may determine how levels of 5HTT mRNA are influenced by promoter methylation. We examined the association of 5HTT gene methylation, which influences gene expression, and the 5HTTLPR genotype before antidepressant treatment and expression before and after treatment. The aims of this study were (1) to investigate the association between 5HTT methylation or expression in leukocytes and depression and (2) to investigate a possible effect of 5HTT methylation, expression, and genotype on clinical symptoms in MDD. The 5HTTLPR genotype was significantly associated with mean methylation levels in patients only (patients: r = 0.40, p = 0.035, controls: p = 0.96). The mean methylation level was significantly increased in patients compared with controls (patients: 5.30 +/- 0.24, controls: 4.70 +/- 0.19, unpaired t-test, p = 0.04). 5HTT expression using real-time PCR and Taqman probes was increased in unmedicated patients compared with controls and then decreased 8 weeks after antidepressant treatment. The mean 5HTT expression level was not associated with the 5HTTLPR genotype in patients or controls. Increased depressive symptoms were related to decreased levels of methylation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27005687 TI - Glutamine promotes intestinal SIgA secretion through intestinal microbiota and IL 13. AB - SCOPE: Glutamine supplementation enhances secretory IgA (SIgA) production in the intestine, but the mechanism is largely unknown. We examined this issue using a mouse model. METHODS AND RESULTS: In mouse model, glutamine supplementation increased both SIgA abundance in intestinal luminal contents and IgA(+) plasma cell numbers in the mouse ileum, and decreased bacterial loads in mouse mesenteric lymph nodes. Glutamine supplementation increased mouse ileal expression of cytokines associated with T cell-dependent and T cell-independent pathways of SIgA induction, including IL-5, IL-6, IL-13, transforming growth factor (TGF-beta), a proliferation-inducing ligand (APRIL), B cell-activating factor (BAFF), vasoactive intestinal peptide (VIP) receptor, and retinal dehydrogenases. Injecting an IL-13 antibody during glutamine supplementation reduced J-chain expression in the mouse ileum. Glutamine supplementation increased bacterial invasion into the mouse ileal wall, while disrupting the mouse intestinal microbiota abrogated the influence of glutamine supplementation on SIgA secretion. CONCLUSION: Glutamine supplementation appears to enhance SIgA secretion in the mouse intestine through the intestinal microbiota and subsequently through T cell-dependent and T cell-independent pathways. PMID- 27005688 TI - The Efficacy and Safety of Knotless Barbed Sutures in the Surgical Field: A Systematic Review and Meta-analysis of Randomized Controlled Trials. AB - The knotless barbed suture is an innovative type of suture that can accelerate the placement of sutures and eliminate knot tying. However, the outcomes of previous studies are still confounding. This study reviewed the application of different types of barbed sutures in different surgeries. We searched PubMed, EMBASE, CENTRAL and ClinicalTrials.gov to identify randomized controlled trials (RCTs) addressing the application of barbed sutures up to Feb. 2015. Two reviewers independently screened the literature and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.3 software. Sensitivity analysis and subgroup analysis was performed. Seventeen RCTs (low to moderate risk of bias) involving 1992 patients were included. Compared with conventional sutures, the barbed suture could reduce suture time (SMD=-0.95, 95%CI -1.43 to -0.46, P = 0.0001) and the operative time (SMD=-0.28, 95%CI -0.46 to -0.10, P = 0.003), not significantly increase the estimated blood loss (SMD= 0.09, 95%CI -0.52 to 0.35, P = 0.70), but could lead to more postoperative complications (OR = 1.43, 95%CI 1.05 to 1.96, P = 0.03), These results varied in subgroups. Thus, barbed sutures are effective in reducing the suture and operative time, but the safety evidences are still not sufficient. It need be evaluated based on special surgeries and suture types before put into clinical practice. PMID- 27005689 TI - Merging of memory effect and anion intercalation: MnOx-decorated MgAl-LDO as a high-performance nano-adsorbent for the removal of methyl orange. AB - MnOx-decorated MgAl layered double oxide (M-LDO) was fabricated via merging of memory effect and anion intercalation, accompanied by the reduction/calcination process. The as-obtained nanocomposites were characterized by scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (XRD) and N2 adsorption-desorption. To clarify the detailed formation mechanism, optimized calcination temperature/time and temperature for methyl orange (MO) adsorption were investigated. Adsorption experiments showed that the adsorption behaviour fitted well with a Langmuir isotherm and pseudo-second-order model, and the maximum adsorption capacity calculated from the Langmuir model was 555.55 mg g(-1). The adsorption process was exothermic and spontaneous in nature. Moreover, the used adsorbent could be regenerated for at least five cycles (94% removal retained) through a thermal procedure, indicating that the M-LDO hybrid is a promising adsorbent with promising ability to remove anionic dye pollutants from wastewater. PMID- 27005690 TI - Consensus-based training and assessment model for general surgery. AB - BACKGROUND: Surgical education is becoming competency-based with the implementation of in-training milestones. Training guidelines should reflect these changes and determine the specific procedures for such milestone assessments. This study aimed to develop a consensus view regarding operative procedures and tasks considered appropriate for junior and senior trainees, and the procedures that can be used as technical milestone assessments for trainee progression in general surgery. METHODS: A Delphi process was followed where questionnaires were distributed to all 17 Canadian general surgery programme directors. Items were ranked on a 5-point Likert scale, with consensus defined as Cronbach's alpha of at least 0.70. Items rated 4 or above on the 5-point Likert scale by 80 per cent of the programme directors were included in the models. RESULTS: Two Delphi rounds were completed, with 14 programme directors taking part in round one and 11 in round two. The overall consensus was high (Cronbach's alpha = 0.98). The training model included 101 unique procedures and tasks, 24 specific to junior trainees, 68 specific to senior trainees, and nine appropriate to all. The assessment model included four procedures. CONCLUSION: A system of operative procedures and tasks for junior- and senior-level trainees has been developed along with an assessment model for trainee progression. These can be used as milestones in competency-based assessments. PMID- 27005691 TI - Campylobacter and Salmonella are prevalent in broiler farms in Kyushu, Japan: results of a 2-year distribution and circulation dynamics audit. AB - AIM: To elucidate the distribution and circulation dynamics of Campylobacter and Salmonella in Japanese chicken broiler flocks. METHODS AND RESULTS: A 2-year investigation of the distribution of Campylobacter and Salmonella was conducted in 25 broiler flocks at nine farms in Japan from 2013 to 2014. Campylobacter and Salmonella tested positive in 11 (44.0%) and 24 (96.0%) broiler flocks respectively. One hundred and ninety-five Campylobacter and 184 Salmonella isolates were characterized into 12 Campylobacter (including two novel genotypes) and three Salmonella MLST genotypes. Only Salmonella isolation between caecal and environmental samples were significantly correlated. Further, one litter sample tested positive for Salmonella before new chicks were introduced. The Campylobacter strains rapidly lost culturability within 2-18 days; in contrast, the Salmonella strains survived from 64-211 days in artificially inoculated water samples. CONCLUSION: No persistent circulation-mediated Campylobacter contamination was observed. In contrast, circulation of Salmonella in broiler houses was seen, apparently due to the litter excreted from broiler flocks, as well as Salmonella-contaminated water and feed. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper provides the distribution, genotypic data and circulation dynamics of Campylobacter and Salmonella as recently observed in Japanese chicken broiler farms. PMID- 27005692 TI - Extrahepatic manifestations of hepatitis E virus. AB - Hepatitis E virus can cause acute, fulminant and chronic hepatitis and has been associated with a range of extrahepatic manifestations. Guillain-Barre syndrome, neuralgic amyotrophy and encephalitis are the main neurological manifestations associated with acute and chronic hepatitis E virus infection. Renal injuries have been also reported, including membranoproliferative glomerulonephritis with or without cryoglobulinemia and membranous glomerulonephritis. Acute pancreatitis, haematological disorders and other autoimmune extrahepatic manifestations of hepatitis E virus, such as myocarditis and thyroiditis, have been also reported. In this comprehensive article, we review all published reports describing hepatitis E virus-associated extrahepatic manifestations. PMID- 27005693 TI - The hepatitis E virus: a likely cause of extrahepatic diseases! PMID- 27005694 TI - Causation by HEV of extrahepatic manifestations remains unproven. PMID- 27005695 TI - Transfusion strategies in patients with cirrhosis: less is more. PMID- 27005696 TI - Response to 'WFA(+)-M2BP: a novel biomarker with diagnostic and therapeutic implications in liver diseases'. PMID- 27005697 TI - Platelet: A friend or foe of patients with hepatoma? PMID- 27005698 TI - Learning stochastic process-based models of dynamical systems from knowledge and data. AB - BACKGROUND: Identifying a proper model structure, using methods that address both structural and parameter uncertainty, is a crucial problem within the systems approach to biology. And yet, it has a marginal presence in the recent literature. While many existing approaches integrate methods for simulation and parameter estimation of a single model to address parameter uncertainty, only few of them address structural uncertainty at the same time. The methods for handling structure uncertainty often oversimplify the problem by allowing the human modeler to explicitly enumerate a relatively small number of alternative model structures. On the other hand, process-based modeling methods provide flexible modular formalisms for specifying large classes of plausible model structures, but their scope is limited to deterministic models. Here, we aim at extending the scope of process-based modeling methods to inductively learn stochastic models from knowledge and data. RESULTS: We combine the flexibility of process-based modeling in terms of addressing structural uncertainty with the benefits of stochastic modeling. The proposed method combines search trough the space of plausible model structures, the parsimony principle and parameter estimation to identify a model with optimal structure and parameters. We illustrate the utility of the proposed method on four stochastic modeling tasks in two domains: gene regulatory networks and epidemiology. Within the first domain, using synthetically generated data, the method successfully recovers the structure and parameters of known regulatory networks from simulations. In the epidemiology domain, the method successfully reconstructs previously established models of epidemic outbreaks from real, sparse and noisy measurement data. CONCLUSIONS: The method represents a unified approach to modeling dynamical systems that allows for flexible formalization of the space of candidate model structures, deterministic and stochastic interpretation of model dynamics, and automated induction of model structure and parameters from data. The method is able to reconstruct models of dynamical systems from synthetic and real data. PMID- 27005699 TI - Synthesis and Evaluation of Potent KCNQ2/3-Specific Channel Activators. AB - KQT-like subfamily (KCNQ) channels are voltage-gated, noninactivating potassium ion channels, and their down-regulation has been implicated in several hyperexcitability-related disorders, including epilepsy, neuropathic pain, and tinnitus. Activators of these channels reduce the excitability of central and peripheral neurons, and, as such, have therapeutic utility. Here, we synthetically modified several moieties of the KCNQ2-5 channel activator retigabine, an anticonvulsant approved by the U.S. Food and Drug Administration. By introducing a CF3-group at the 4-position of the benzylamine moiety, combined with a fluorine atom at the 3-position of the aniline ring, we generated Ethyl (2 amino-3-fluoro-4-((4-(trifluoromethyl)benzyl)amino)phenyl)carbamate (RL648_81), a new KCNQ2/3-specific activator that is >15 times more potent and also more selective than retigabine. We suggest that RL648_81 is a promising clinical candidate for treating or preventing neurologic disorders associated with neuronal hyperexcitability. PMID- 27005701 TI - Synthesis of highly functionalized oligobenzamide proteomimetic foldamers by late stage introduction of sensitive groups. AB - alpha-Helix proteomimetics represent an emerging class of ligands that can be used to inhibit an array of helix mediated protein-protein interactions. Within this class of inhibitor, aromatic oligobenzamide foldamers have been widely and successfully used. This manuscript describes alternative syntheses of these compounds that can be used to access mimetics that are challenging to synthesize using previously described methodologies, permitting access to compounds functionalized with multiple sensitive side chains and accelerated library assembly through late stage derivatisation. PMID- 27005700 TI - Hydrogen Sulfide in Renal Physiology and Disease. AB - SIGNIFICANCE: Hydrogen sulfide (H2S) has only recently gained recognition for its physiological effects. It is synthesized widely in the mammalian tissues and regulates several biologic processes ranging from development, angiogenesis, neurotransmission to protein synthesis. Recent Advances: The aim of this review is to critically evaluate the evidence for a role for H2S in kidney function and disease. CRITICAL ISSUES: H2S regulates fundamental kidney physiologic processes such as glomerular filtration and sodium reabsorption. In kidney disease states H2S appears to play a complex role in a context-dependent manner. In some disease states such as ischemia-reperfusion and diabetic kidney disease it can serve as an agent that ameliorates kidney injury. In other diseases such as cis-platinum induced kidney disease it may mediate kidney injury although more investigation is needed. Recent studies have revealed that the actions of nitric oxide and H2S may be integrated in kidney cells. FUTURE DIRECTIONS: Further studies are needed to understand the full impact of H2S on kidney physiology. As it is endowed with the properties of regulating blood flow, oxidative stress, and inflammation, H2S should be investigated for its role in inflammatory and toxic diseases of the kidney. Such in-depth exploration may identify specific kidney diseases in which H2S may constitute a unique target for therapeutic intervention. Antioxid. Redox Signal. 25, 720-731. PMID- 27005702 TI - Arginine selective reagents for ligation to peptides and proteins. AB - A new class of arginine-specific bioconjugation reagents for protein labeling has been developed. This method utilizes a triazolyl-phenylglyoxal group on the probe molecule that reacts selectively with the guandinyl group of Arg residues in a protein or peptide. The reaction proceeds in neutral to basic bicarbonate buffers and is selective for arginine residues in peptides and folded proteins. Importantly, the triazolyl-phenylglyoxal group can be introduced into complex molecules containing alkyne groups using CuAAC chemistry, providing a robust approach for the generation of phenylglyoxal reactive groups into molecules to be covalently attached onto the surface of proteins. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27005703 TI - Charge transfer induced activity of graphene for oxygen reduction. AB - Tetracyanoethylene (TCNE), with its strong electron-accepting ability, was used to dope graphene as a metal-free electrocatalyst for the oxygen reduction reaction (ORR). The charge transfer process was observed from graphene to TCNE by x-ray photoelectron spectroscopy and Raman characterizations. Our density functional theory calculations found that the charge transfer behavior led to an enhancement of the electrocatalytic activity for the ORR. PMID- 27005704 TI - Prohibitin-induced, obesity-associated insulin resistance and accompanying low grade inflammation causes NASH and HCC. AB - Obesity increases the risk for nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. However, the underlying mechanisms involved in the disease process remain unclear. Recently, we have developed a transgenic obese mouse model (Mito-Ob) by prohibitin mediated mitochondrial remodeling in adipocytes. The Mito-Ob mice develop obesity in a sex-neutral manner, but obesity-associated adipose inflammation and metabolic dysregulation in a male sex-specific manner. Here we report that with aging, the male Mito-Ob mice spontaneously develop obesity-linked NASH and hepatocellular carcinoma (HCC). In contrast, the female Mito-Ob mice maintained normal glucose and insulin levels and did not develop NASH and HCC. The anti-inflammatory peptide ghrelin was significantly upregulated in the female mice and down regulated in the male mice compared with respective control mice. In addition, a reduction in the markers of mitochondrial content and function was found in the liver of male Mito-Ob mice with NASH/HCC development. We found that ERK1/2 signaling was significantly upregulated whereas STAT3 signaling was significantly down regulated in the tumors from Mito-Ob mice. These data provide a proof-of-concept that the metabolic and inflammatory status of the adipose tissue and their interplay at the systemic and hepatic level play a central role in the pathogenesis of obesity-linked NASH and HCC. PMID- 27005705 TI - Relation between time interval from antenatal corticosteroids administration to delivery and neonatal outcome in twins. AB - AIM: The aim of this study was to evaluate the perinatal outcome in twins, who were administered one complete course of antenatal corticosteroids (ACS) depending on the time interval from corticosteroids to delivery. METHODS: We carried out a retrospective analysis of medical data of women with twins who received a course of ACS and delivered before 34 weeks within or beyond 7 days after ACS were given. Among 652 twin deliveries between 2006 and 2014, 106 met the criteria (50 patients delivered <7 days and 56 >= 7 days after ACS administration). RESULTS: There were no differences in the mean gestational age at labor, mean birthweight, perinatal mortality or newborns' general condition between women who delivered <7 and >=7 days after corticosteroids. Newborns in the >=7 days group suffered from respiratory disorders significantly more often (74.1% vs 54.5%, P = 0.003) and were hospitalized longer (42.6 +/- 19.1 vs 33.4 +/- 21.7 days, P < 0.001). Significantly more infants in the <7 days group were administered antibiotics (55.6% vs 25%, P = 0.001). In the multiple logistic regression analysis, the only factors significantly influencing the incidence of respiratory complications in twins were delivery following ACS therapy within 7 days (adjusted odds ratio, 0.16; 95% confidence interval, 0.02-0.90) and female sex (adjusted odds ratio, 0.71; 95% confidence interval 0.40-0.90). CONCLUSION: There is a relation between neonatal outcomes in twins and time interval between ACS administration and birth. Therefore, a single ACS course should be administered with caution in order to allow for the completion of the treatment without exceeding an interval of 7 days to delivery. (c) 2016 Japan Society of Obstetrics and Gynecology. PMID- 27005706 TI - Long-term Follow-up of Cytomegalovirus Retinitis in Non-HIV Immunocompromised Patients: Clinical Features and Visual Prognosis. AB - PURPOSE: To evaluate clinical features and long-term visual outcome of cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus (HIV) infection, and to determine factors that predict visual outcome. DESIGN: Retrospective cohort study. METHODS: Consecutive patients with CMV retinitis without HIV infection were reviewed. Main outcome measures included clinical features, proportion of eyes with 6-month and final visual acuity (VA) <20/70 and <20/400, and odds ratios of factors associated with poor visual outcome. RESULTS: A total of 20 eyes from 13 patients were included with a median follow-up time of 17 months. All had at least 6 months of follow-up except 1 patient who died from sepsis at 1 month. At presentation, 50% of eyes had VA <20/70 and 25% had VA <20/400. Zone 1 involvement occurred in 55% and vitreous haze >=grade 2+ occurred in 25%. Recurrence occurred in 33.3% at a mean time of 6.4 +/- 3.3 weeks after discontinuation of anti-CMV therapy. The retinal detachment rate was 21.7% per eye-year and mortality rate was 11.7% per person-year. At final visit, 60% had VA <20/70 and 35% had VA <20/400. Macular involvement was significantly associated with poor final VA <20/400 (odds ratio = 25.00, P = .016). CONCLUSIONS: CMV retinitis without HIV infection was often aggressive at presentation. Significant intraocular inflammation was not uncommon. The long-term visual outcome was poor, especially in those with macular involvement. PMID- 27005707 TI - Assessing the Effects of Participant Preference and Demographics in the Usage of Web-based Survey Questionnaires by Women Attending Screening Mammography in British Columbia. AB - BACKGROUND: Increased usage of Internet applications has allowed for the collection of patient reported outcomes (PROs) and other health data through Web based communication and questionnaires. While these Web platforms allow for increased speed and scope of communication delivery, there are certain limitations associated with this technology, as survey mode preferences vary across demographic groups. OBJECTIVE: To investigate the impact of demographic factors and participant preferences on the use of a Web-based questionnaire in comparison with more traditional methods (mail and phone) for women participating in screening mammography in British Columbia, Canada. METHODS: A sample of women attending the Screening Mammography Program of British Columbia (SMPBC) participated in a breast cancer risk assessment project. The study questionnaire was administered through one of three modes (ie, telephone, mail, or website platform). Survey mode preferences and actual methods of response were analyzed for participants recruited from Victoria General Hospital. Both univariate and multivariate analyses were used to investigate the association of demographic factors (ie, age, education level, and ethnicity) with certain survey response types. RESULTS: A total of 1192 women successfully completed the study questionnaire at Victoria General Hospital. Mail was stated as the most preferred survey mode (509/1192, 42.70%), followed by website platform (422/1192, 35.40%), and telephone (147/1192, 12.33%). Over 80% (955/1192) of participants completed the questionnaire in the mode previously specified as their most preferred; mail was the most common method of response (688/1192, 57.72%). Mail was also the most preferred type of questionnaire response method when participants responded in a mode other than their original preference. The average age of participants who responded via the Web-based platform (age 52.9, 95% confidence interval [CI] 52.1 53.7) was significantly lower than those who used mail and telephone methods (age 55.9, 95% CI 55.2-56.5; P<.001); each decade of increased age was associated with a 0.97-fold decrease in the odds of using the website platform (P<.001). Web based participation was more likely for those who completed higher levels of education; each interval increase leading to a 1.83 increase in the odds of website platform usage (P<.001). Ethnicity was not shown to play a role in participant preference for the website platform (P=.96). CONCLUSIONS: It is beneficial to consider participant survey mode preference when planning to collect PROs and other patient health data. Younger participants and those of higher education level were more likely to use the website platform questionnaire; Web-based participation failed to vary across ethnic group. Because mail questionnaires were still the most preferred survey mode, it will be important to employ strategies, such as user-friendly design and Web-based support, to ensure that the patient feedback being collected is representative of the population being served. PMID- 27005708 TI - Gestational Diabetes Mellitus - A Public Health Concern in Rural Communities of Nepal. AB - BACKGROUND: Gestational Diabetes Mellitus (GDM) is in increasing trend recently. It is associated with adverse effects on both mother and fetus. Thus, diagnosis of GDM is an important public health issue. This study aimed to determine the frequency of gestational diabetes mellitus in three rural districts of Nepal. METHODS: A hospital based study was conducted in three districts representing mountain, hill and Terai belts of Nepal during the period of July 2009 to June 2010. A total of 564 pregnant women were interviewed and tested for blood glucose as per WHO guideline Results: In Nepal, only 2.5% of pregnant women had GDM according to WHO criteria while it was 6.6% according to IADPSG criteria. Overall mean blood glucose among pregnant women was 72.1 (fasting) and 95.8 (after 2 hrs of 75 gm glucose intake) in which it was 62.8, and 75.1 in Dhading, 78.7 and 88.9 in Dhangadhi, and 98.3 and 99.3 in Solukhumbu districts respectively. Pregnant women with increased age were significantly at high risk of having GDM than those of younger women (p=0.04). There were non-significant differences in GDM by District, Ethnic group and family history of DM. CONCLUSIONS: Gestational diabetes in the rural areas of Nepal is variable with two different criterias (2.5% vs 6.56%). Increasing age was an important influencing factor. Special attention should be given on women with increasing age. There was no significant difference in prevalence of GDM in three ecobelts of Nepal despite of altitude and cultural variability. PMID- 27005709 TI - Menopausal Health Status of Women of Kapilvastu District of Nepal. AB - BACKGROUND: Women face numerous health problems in their post-reproductive and menopausal years, including issues such as pelvic pain, incontinence and obstetric fistula. In Nepal, the importance of these health issues is increasing with the aging of the population, yet women are often unable to access adequate health care due to entrenched gender structures and misconceptions regarding menopause. This study aimed to describe the prevalence of menopause, the associated health problems and their severity amongst women aged 40-60 years in Kapilvastu. METHODS: A descriptive study was conducted in Kapilvastu district. Multi stage cluster sampling technique was adopted: Illakas of Kapilvastu were identified, then one Village Development Committee (VDC) from each Illaka of the district, and two wards from each of these VDCs, were selected randomly. RESULTS: The median age of onset of menopause was 47 years (25 th and 75 percentiles = 43 and 50 years), and >90% of women had entered menopause by 54. All symptoms in the Menopause Rating Scale were experienced to some extent by at least 30% of women, even amongst the premenopausal group. The most common problems experienced by menopausal women were: sexual problems (81.7%, 95%CI: 78.0-85.4), physical and mental exhaustion (81.5%, 95%CI: 77.8-85.2) and joint and muscular discomfort (78.5%, 95%CI: 74.6-82.4). The symptoms most frequently deemed "severe" or "very severe" were: sexual problems (40.5%), joint and muscular discomfort (27.4%), and sleep problems (21.0%). th CONCLUSIONS: Middle-aged women in Kapilvastu experienced menopausal symptoms to a substantial degree. The prevalence and severity of these symptoms increased with the menopausal transition, and with increasing age. Menopause itself did not appear to be the primary risk factor for typical "menopausal" symptoms. PMID- 27005710 TI - Male Participation in Family Planning: Human Behaviour Perspective. AB - BACKGROUND: Family planning (FP) is one of the major components of reproductive health and its goal is to prevent unwanted pregnancies and regulate wanted pregnancies, thereby ensuring the health of mothers and children. It also aims at regulating the population in order to maintain the vital balance between development and the environment. Ideally, FP depends on the efforts of a couple where the man and woman are equally responsible and accountable. In reality, however, this is not the case. It is in this background that the present study aims at examining the nature and level of male participation in preventing unwanted pregnancies and the factors that influence male participation in FP. METHODS: The data for the study was derived using mixed methods, drawing from both quantitative and qualitative approaches. The research design was cross sectional, descriptive and observational. RESULTS: Despite the high level of knowledge and awareness about FP among the respondents, it was found that male participation in FP continues to remain very low. The multidimensional factors influencing their participation include education of the couple (the unadjusted odds ratio of higher education level of respondents is 2.182 and the adjusted OR is 1.972; and the unadjusted OR of higher education level of the spouse is 2.030, and the adjusted OR is 1.570), and economic condition (the unadjusted OR of higher income is 2.272 and the adjusted OR is 2.436) of family. Male participation in FP was found to be higher in rural areas (69.8 %) and among Dalits (72.5%). Other factors include social stigma and religious practice, patriarchal notions, gender roles and individual characteristics. CONCLUSIONS: Male participation plays a crucial role in population management, but patriarchal notions, socioculturally defined gender roles, combined with the inefficiency of the current FP programme, and biological factors contribute towards keeping male participation very low. PMID- 27005711 TI - Magnetic Resonance Imaging Findings in Degenerative Disc Disease of Cervical Spine in Symptomatic Patients. AB - BACKGROUND: The pathophysiological findings demonstrated in cervical spine in Magnetic Resonance Imaging (MRI) can explain only partly the occurrence of neck and shoulder pain. This study aims to evaluate the occurrence of cervical degenerative disc pathologies in symptomatic patient with neck pain and radiculopathy. METHODS: The study was a retrospective and institutional record based descriptive study carried out for the duration of 3yrs in a well-equipped imaging center. Only MRI performed for neck pain with or without radiculopathy with complete clinical form was included in the study. MRI findings were entered in SPSS spread sheet and analyzed using SPSS 19.0. RESULTS: A total of 750 MRI was reviewed among which 571(76.13%) had cervical degenerative disc pathology. Disc degeneration and disc bulge was the most common finding, followed by neural foramina stenosis, disc herniation and myelopathic changes. Disc degeneration and disc bulge was seen more frequently in patients older than 40 years than those less than 40 years. Disc herniation was rare in extremes of age and noted predominantly in productive population between 3 rd and 6 th decade of life. CONCLUSIONS: Disc degeneration and global disc bulge were predominant findings in symptomatic patients increasing with the age. Disc herniation and neural foraminal stenosis were common changes seen associated with neck pain with or without radiculopathy and were predominant in productive age group. PMID- 27005712 TI - Ventricular Tachyarrhythmia after Aortic Cross Clamp Release in Cardiac Surgeries. AB - BACKGROUND: Ventricular tachyarrhythmia (VT/VF) after aortic artery cross clamp release in cardiac surgery is common and the occurrence has been described but the incidence and risk factors are not well defined. This study was designed with the aim to evaluate the prevalence of VT/VF after aortic cross clamp release and to identify risk factors of patients developing such arrhythmias. METHODS: A retrospective observational study 1052 patients over a period of 12 months from March 2011 to February 2012 undergoing various cardiac surgeries with aortic cross clamp were monitored for new-onset ventricular tachyarrhythmia intraoperatively. RESULTS: The prevalence of ventricular tachyarrhythmia was 24.4%. We found age above 30 years, increasing body mass index (BMI), valvular surgeries and male gender as risk factors for VT/VF after cross clamp release in cardiac surgeries. CONCLUSIONS: Ventricular tachyarrhythmia is common following all cardiac surgeries, especially valvular heart diseases. There is a strong relationship between ventricular arrhythmias and age above 30 years, coronary artery bypass surgery (CABG), high (BMI) and male gender. It is essential for intense monitoring of these patients. PMID- 27005713 TI - Bacteriological Profile of Neonatal Sepsis in Neonatal Intermediate Care Unit of Central Paediatric Referral Hospital in Nepal. AB - BACKGROUND: Sepsis is one of the leading causes of neonatal morbidity and mortality. Because of difference in local epidemiology and possible variation with time, regular monitoring and updates on pathogen and their antimicrobial sensitivity pattern is important for prevention and treatment. METHODS: A retrospective descriptive study was carried out among cases of neonatal sepsis admitted in neonatal intermediate care unit of Kanti Children's hospital from August 2014 to August 2015. The data was collected from medical records of neonatal intermediate care unit and microbiology department and analyzed using SPSS version 20. RESULTS: There were 644 admissions, among which 210 (32%)were suspected of having neonatal sepsis. Thirty(14%) of the suspected cases had positive blood culture. Proportions of late and early onset were 25 (83.3%) and 5(17.7%) respectively.In blood culture Staphylococcus aureus was the most common organism(80%),followed by Coagulase negative Staphylococcus (6.66%), Acinetobacter (6.66%), Enterobacter species(3.33%) and Morgonellamorgoni (3.33.5%).Gram positive organisms were isolated in all cases of early onset sepsis and in 84% of late onset sepsis. Most of the isolated organisms showed sensitivity to amikacin, cloxacillin, ciprofloxacin and vancomycin. CONCLUSIONS: This study has indicated possible emergence of Staphylococcus aureus as the dominant cause of neonatal sepsis. Cloxacillin, amikacin, ciprofloxacin have high proportion of efficacy against the commonly isolated bacteria in neonatal sepsis. PMID- 27005714 TI - Morphological Changes in Degenerative Disc Disease on Magnetic Resonance Imaging: Comparison Between Young and Elderly. AB - BACKGROUND: Morphological changes implicated in low back are complicated by additional age related degenerative changes in spine, which increases with aging. This study aims to compare the morphological MRI findings in young and elderly patients with low back pain and also correlate them with the clinical symptoms. METHODS: The study was a retrospective hospital record based comparative study carried out in a Teaching Hospital. MRI performed for patients with low back pain during May 2012 to October 2012 were reviewed. The MRI findings were compared between below 60 years and at and above 60 years and were also correlated with symptoms. RESULTS: A total of 301 MRI met the inclusion criteria out of which 228(75.74%) were young adults and 73(24.25%) were elderly adults. Degenerative changes and disc bulge was more common in elderly. Disc herniations including disc prolapse was more common in young adults. Disc protrusion involving L4-L5 was most common in the elderly while L5-S1 was most common in young adults. Nerve root compression was noted more commonly in the young adults. Radiculopathy was associated with grade III nerve root compression and paramedian disc protrusion in young adults while no such association was noted in elderly. No association of radiculopathy with presence of degenerative changes, spinal stenosis was noted in both groups. CONCLUSIONS: Degenerative changes are more common in elderly while disc herniations are more common in young adults. Morphologic changes do correlate with symptoms in young adults to some extent while they do not correlate in elderly. PMID- 27005715 TI - Glycemic Status in Organophosphorus Poisoning. AB - BACKGROUND: Organophosphorus(OP) poisoning, in addition to its cholinergic manifestations shows metabolic derangements leading to hyperglycemia. Apart from inhibiting acetylcholinesterase it also induces oxidative stress to exhibit this manifestation. The present study aims to assess the glycemic status of OP poisoned patients and its association with various factors in OP poisoning like oxidative stress and dose of atropine. METHODS: This is a prospective study which recruited 102 patients above 18 years of age with history of OP poisoning. They were categorized into 3 grades-mild, moderate and severe based on the Peradeniya Organophosphorus Poisining Scale. The routine biochemical parameters along with serum malondialdehyde (MDA) and cholinesterase were estimated in the study group. RESULTS: Hyperglycemia and glycosuria were observed, with majority cases of hyperglycemia (57%) noticed in the severe group. There was a rise in the random plasma glucose (RPG), serum malondialdehyde (MDA), total dose of atropine across the groups along with a fall in the serum cholinesterase with increase in severity of poisoning. The fall in plasma glucose at the time of discharge was significant in all three groups when compared to the admission random plasma glucose(RPG) level. This transient hyperglycemia exhibited a significant positive association with serum MDA and dose of atropine administered during treatment (p<0.05). CONCLUSIONS: Glycemic status in OP poisoning may play a role in identifying the severity of poisoning at the time of admission. PMID- 27005716 TI - Factors Associated with Tobacco Use among Female Adolescent Students in Dharan Municipality of Eastern Nepal. AB - BACKGROUND: Rising trend of female tobacco use is a serious concern in South East Asia Region. Gender differences in tobacco use is likely to be reduced in the future with continuous modernization in low and middle income countries like Nepal. METHODS: Pre tested self administered questionnaire adapted from Global Youth Tobacco Survey was used to assess tobacco use among the representative sample of 618 female adolescent students selected by stratified random sampling from different schools of Dharan Municipality from July 2011 to July 2012. Chi square test and binary logistic regression were applied. Probability of significance was set at 5%. RESULTS: Prevalence of ever tobacco use was 4% (95% CI 2.4% to 5.5%).The mean age of initiation of tobacco smoking was 13.58 years (SD =1.71) and that of tobacco chewing was 13.80 years (SD = 1.47). More than a third of the tobacco users (36%) consumed tobacco at home whereas three fifth (60%) of the users purchased tobacco directly from the shops.The major reasons behind initiation of tobacco use were for recreational use (32%), pressure from friends (32%) and to relieve pain or stress in life (28%). Multivariate analysis showed that ever tobacco use was significantly associated with ever use of alcohol (AOR: 7.54, 95% CI: 2.61 to 21.78). CONCLUSIONS: School and college based awareness raising campaigns are required for female adolescent students to counter the rising tobacco use (smoking and smokeless). Interventions like health education should focus on tobacco to prevent initiation during adolescence. PMID- 27005717 TI - Dermatophytic Infections among the Patients Attending Di Skin Hospital and Research Center at Maharajgunj Kathmandu. AB - BACKGROUND: Dermatophytosis is the common and most significant superficial fungal infections because of their widespread involvement among the people all over the world. The clinical presentation, though very typical of ringworm infection, is often confused with other skin disorders, making laboratory diagnosis and confirmation necessary. The aim of this research is to study different clinical variants of dermatophytosis and its associated risk factor among the patients attending Di Skin Hospital and Research Center. METHODS: A descriptive cross sectional study design was used. Total of 110 samples collected from suspected cases of dermatophytosis were studied among the patients attending DI Skin Hospital and Research Center at Maharajgunj, Kathmandu, Nepal. Skin, hair and nail specimens taken from the patients were processed by direct microscopy and culture using a standard protocol. Macroscopic appearance and microscopic morphology of micro and macroconidia were studied for proper identification of dermatophytes. Data were analyzed using the statistical package for the social sciences (SPSS) version 20 for windows. RESULTS: Dermatophytosis was more common in the age group of 21-30 (29.1%) years and was more predominant among male population with male to female ratio being 1.39:1. Among the total number of dermatophytosis cases only 52.72% showed fungal elements in KOH preparation and only 43.63% were culture positive. Most common clinical type was tinea corporis (29.1%) followed by tinea cruris (18.2%). Among the total isolates T. rubrum was most common (58.33%) followed by T. mentagrophytes (20.83%), other Trichophyton spp (12.5%) and Microsporum gypseum (8.33%). Most of the positive cases used to take bath, change their dresses and innerwear only once a week. Similarly, Sweating nature could be the possible cause for dermatophytic infection (P=0.006 at CI=95%) and also there was a significant relation between the sharing habit of dress materials and positive cases (P=0.033 at CI=95%). Among the total cases, most of the positive cases did not have any knowledge about fungal infection.Study concluded that more the knowledge of fungal infection less the chance of fungal infection (P=0.003 at CI=95%). CONCLUSIONS: Tinea corporis was the commonest clinical pattern and overall predominance in the study was male with 21-30 being most affected age group. T. rubrum forms the commonest aetiological agent of dermatophytosis. Possible cause of dermatophytic infection was due to poor hygienic status and lack of knowledge on fungal infection and its preventive measures. PMID- 27005718 TI - Surveillance of Quality of Medicines Available in the Nepalese Market: A Study from Kathmandu Valley. AB - BACKGROUND: Many countries are having problem of substandard and counterfeit drugs which results in life threatening issues, financial loss of consumers and loss in trust on health system. This study is concerned with the assessment of drugs quality available in the Nepalese market. METHODS: A cross sectional survey was carried out in Kathmandu valley. Five different brands from each eight molecules of drugs (Paracetamol tablet, Cloxacillin capsule, Amlodipine tablet, Metformin tablet, Losartan tablet, Cefixime tablet, Ofloxacin tablet, Carbamazepine tablet) were purposively selected. Registration compliance was verified from Department of Drug Administration (DDA) and laboratorial analysis was done in two different laboratories. RESULTS: Out of 40 drug samples, 90% did not comply with the existing regulatory requirement on labeling and 42.5% brands did not mention about the pharmacopoeial standard. There was no uniformity in mentioning the selflife. Similarly, large variation was seen on price of same generic drugs. Laboratory analysis showed that 40% samples failed to meet the standard among domestic companies and 28% among imported brands. Altogether 32.5% samples were found to be of substandard quality. Only the result of one sample matched with both laboratories. This indicates that there was variation in the selected two laboratories. CONCLUSIONS: The result of this survey indicates that, substandard medicines are available in Nepalese market. Moreover, there is weak regulation and no uniformity in similar pharmaceutical products. A larger study is required to access the quality of pharmaceutical products in the Nepalese market with testing of products in more than two independent laboratories. PMID- 27005719 TI - Acute Pulmonary Embolism after Cesarean Section. AB - Pregnancy is a well-known state of hypercoagubality, increasing the risk of venous thromboembolism (VTE). It is more common with cesarean delivery than vaginal delivery. Pulmonary Embolism (PE) is under diagnosed during pregnancy and postpartum period as majority of signs and symptoms of PE are non-specific. We describe a case of 35-yearold obese female who suffered a syncopal attack following caesarean delivery and was diagnosed to have pulmonary embolism. A high index of suspicion is required for the timely diagnosis and treatment of PE as most of the signs and symptoms of PE are nonspecific. It is important to consider VTE prophylaxis especially in patients with risk factors. PMID- 27005720 TI - Pancreatic Abscess: An Unusual Presentation of Pancreatic Tail Cancer. AB - Pancreatic abscess usually occurs in the setting of pancreatitis especially if complicated by pseudocysts or pancreatic necrosis. On the other hand, pancreatic body and tail cancer is relatively uncommon cancer and rarely does it present as a pancreatic abscess. We describe a 50-year-old man with sepsis due to underlying pancreatic abscess, who was later diagnosed to have pancreatic tail adenocarcinoma with the help of endoscopic ultrasound guided fine needle aspiration cytology. PMID- 27005721 TI - Zika Virus: Yet Another Emerging Threat to Nepal. AB - Zika virus (ZIKV) is a flavivirus with single stranded RNA related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses and is transmitted by Aedes mosquitoes primarily by Aedes aegipti which is widely distributed in Nepal. ZIKV was first identified incidentally in Rhesus monkey in Uganda in 1947 and human infection in 1952; and by now outbreaks of ZIKV disease have been recorded in Africa, the Americas, Asia and the Pacific. The World Health Organization (WHO) has recently declared the ZIKV an international public health emergency. The aim of this paper is to briefly summarize origin, signs, symptoms, transmission, diagnosis, preventions and management of ZIKV and possible threat to Nepal in light of endemicity of other arbovirus infections and common mosquito vector species in Nepal. Keyword: Aedes aegypti; aedes albopictus; zika virus; microcephaly; birth defect; Nepal. PMID- 27005722 TI - Focusing on Women and Children in the Sustainable Development Goals. PMID- 27005723 TI - What the Psychiatrist Needs to Know About Ventricular Assist Devices: A Comprehensive Review. AB - BACKGROUND: The number of patients with end-stage heart failure using mechanical circulatory support has dramatically increased over the past decade. Left ventricular assist devices, the most common type of mechanical circulatory support, can be used as a bridge to transplant, destination therapy, and as a bridge to recovery. As this patient population continues to grow, consultation liaison psychiatrists will become increasingly involved in their care. A thorough biopsychosocial assessment is required to ensure adequate recognition and management of medical, psychiatric, social, and ethical challenges posed by this population. METHODS: We performed a literature review to identify key issues relevant to the practice of consultation-liaison psychiatrists. RESULTS: General functioning of left ventricular assist devices, device types, system components, life with a left ventricular assist device, preoperative evaluation, treatment of psychiatric comorbidities, and end-of-life decision-making are discussed. CONCLUSIONS: Consultation-liaison psychiatrists need to be familiar with the high prevalence of psychopathology in patients implanted with left ventricular assist devices. A detailed biopsychosocial formulation is required to adequately identify and, if possible, resolve a myriad of medical, psychiatric, social, and ethical challenges presented by this population. Future efforts should accurately identify and report specific psychiatric disorders and adverse events within this cohort. PMID- 27005724 TI - Lamotrigine Treatment for Agitation Following Traumatic Brain Injury. PMID- 27005725 TI - Time to Consultation-Liaison Psychiatry Service Referral as a Predictor of Length of Stay. AB - OBJECTIVES: The aim of this study was to determine the relationship between the time to referral (TTR) to psychiatric consultation and the length of stay (LOS) after adjusting for medical comorbity. METHODS: Using a naturalistic study design, we collected and analyzed inpatient consultation-liaison psychiatry service data over a 12-month period from 2 Canadian hospital sites. Data collected included demographic characteristics, referral characteristics, Charlson Comorbidity Index to measure medical comorbidity severity, psychiatric diagnoses, type of psychiatric intervention, and time variables, namely TTR and LOS. We modeled the relationship LOS and TTR after adjusting for Charlson Index using a 3-component finite mixture of exponential regression models. RESULTS: A total of 814 patients were included. The median LOS was 12 days (interquartile range : 4-28 days). Median TTR was 3 days (interquartile range: 1,9), and median Charlson Index was 5 (interquartile range 3,6). Bivariate analysis indicated a strong positive correlation among LOS and TTR (Spearman correlation: 0.77, p < 0.0001) and Charlson Index(Spearman correlation: 0.34, p < 0.0001), respectively. After controlling for Charlson Index, we observe that TTR was significantly associated with LOS in each of the 3 components of the mixture of exponential regression models. Persons with longer TTR have longer expected LOS. Graphical summaries suggest that the mixture of exponential regression model provides a good fit to these LOS response data. CONCLUSIONS: Patients with longer TTR had significantly longer LOS. The association between TTR and LOS holds after controlling for severity of medical comorbidity. Our results support the role of integrated and proactive consultation-liaison psychiatry programs aimed at reducing TTR to improve LOS outcomes. PMID- 27005726 TI - Asymmetric preparation of polysubstituted cyclopentanes by synergistic Pd(0)/amine catalyzed formal [3+2] cycloadditions of vinyl cyclopropanes with enals. AB - We report herein a novel diastereo- and enantiocontrolled preparation of polysubstituted cyclopentanes by the formal [3+2] cycloadditions of vinyl cyclopropanes with enals. In constrast with previously developed strategies, our original approach is based on the synergistic merger of iminium/enamine organocatalysis with palladium(0) catalysis. PMID- 27005729 TI - [CME. Eosinophilia - is a worm responsible?]. PMID- 27005727 TI - Human sperm rheotaxis: a passive physical process. AB - A long-standing question in natural reproduction is how mammalian sperm navigate inside female reproductive tract and finally reach the egg cell, or oocyte. Recently, fluid flow was proposed as a long-range guidance cue for sperm navigation. Coitus induces fluid flow from oviduct to uterus, and sperm align themselves against the flow direction and swim upstream, a phenomenon termed rheotaxis. Whether sperm rheotaxis is a passive process dominated by fluid mechanics, or sperm actively sense and adapt to fluid flow remains controversial. Here we report the first quantitative study of sperm flagellar motion during human sperm rheotaxis and provide direct evidence indicating that sperm rheotaxis is a passive process. Experimental results show that there is no significant difference in flagellar beating amplitude and asymmetry between rheotaxis-turning sperm and those sperm swimming freely in the absence of fluid flow. Additionally, fluorescence image tracking shows no Ca(2+) influx during sperm rheotaxis turning, further suggesting there is no active signal transduction during human sperm rheotaxis. PMID- 27005728 TI - Cytochrome P450 CYP6DA2 regulated by cap 'n'collar isoform C (CncC) is associated with gossypol tolerance in Aphis gossypii Glover. AB - Cotton plants accumulate phytotoxins, such as gossypol and related sesquiterpene aldehydes, to resist insect herbivores. The survival of insects exposed to toxic secondary metabolites depends on the detoxification metabolism mediated by limited groups of cytochrome P450. Gossypol has an antibiotic effect on Aphis gossypii, and as the concentrations of gossypol were increased in the present study, the mortality of cotton aphids increased from 4 to 28%. The fecundity of the cotton aphids exposed to gossypol was also significantly reduced compared with the control. The transcriptional levels of CYP6DA2 in cotton aphids were significantly induced when exposed to gossypol, and knockdown of the CYP6DA2 transcripts by RNA interference (RNAi) significantly increased the toxicity of gossypol to cotton aphids. To further understand the gossypol regulatory cascade, the 5'-flanking promoter sequences of CYP6DA2 were isolated with a genome walker, and the promoter was very active and was inducible by gossypol. Co-transfection of the cap 'n' collar isoform C (CncC) and CYP6DA2 promoters dramatically increased the expression of CYP6DA2, and suppression of the CncC transcripts by RNAi significantly decreased the expression levels of CYP6DA2, and significantly increased the toxicity of gossypol to cotton aphids. Thus, the transcriptional regulation of CYP6DA2 involved the transcriptional factor CncC. PMID- 27005731 TI - [Neurorehabilitation in Parkinson's disease]. AB - Parkinson's disease (PD) is a chronic neurodegenerative disease which is characterized by the cardinal symptoms akinesia, rigidity, rest tremor and postural instability. Besides PD features also a wide range of non-motor symptoms. Physical activity is recommended for all stages of PD and may hypothetically even have a positive influence on the course of the disease. Rehabilitative treatments become increasingly important in the advanced stage of the disease and include mainly physiotherapy, occupational therapy and speech therapy. Neurorehabilitation is arguably most important for the treatment of axial symptoms such as freezing, hypophonia, dysphagia, postural instability and postural disturbances that respond poorly to drug therapy. This article provides an overview of current developments in the field of neurorehabilitation in PD. PMID- 27005732 TI - [Trauma-focused psychotherapies: what are the commonalities?]. AB - A number of evidence-based psychotherapeutic approaches for the treatment of posttraumatic stress disorder (PTSD) are available. They differ in various ways, however, they also have a number of commonalities. Given this situation, clinicians may wonder which treatment program to use, or more specifically, which treatment components are critical for a successful therapy. The following treatment components can be found in almost all effective psychotherapies for PTSD: psycho-education; teaching emotion regulation and coping skills; imaginal exposure, cognitive processing, restructuring and/or meaning making; targeting emotions; and the reorganization of memory functions. The underlying mechanisms of action are not sufficiently investigated. In the future, treatments should be tailored more specifically depending on certain patient characteristics. Also, the additional benefit of interventions aimed at improving resilience remains to be established. PMID- 27005733 TI - [Atypical hemolytic uremic syndrome (aHUS): new insights into pathogenesis leading to novel therapeutic approaches]. AB - The atypical hemolytic-uremic syndrome (aHUS) belongs to the thrombotic mictroangiopathies (TMA). This group of diseases has traditionally been divided on clinical grounds by affected organs into thrombotic-thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), the latter being termed atypical if not preceeded by diarrhea. Tremendous scientific advances of the last two decases have shown that these clinically overlaping syndromes are caused by distinct molecular mechanisms. The definition of clinical syndromes has therefore been replaced by a TMA-classification on a molecular-mechanistic basis. aHUS is caused by an uncontrolled activation of the alternative complement pathway mostly due to genetic defects. These insights and particularly the development of a specific terminal complement inhibitor have revolutionized the treatment of aHUS and considerably improved its prognosis. PMID- 27005734 TI - ["Food addiction" as a possible risk factor for obesity]. AB - The prevalence rates of overweight and obesity are, internationally as well as in Switzerland, increasing in recent years. The neurobiology tries to explore an improved understanding of the central nervous causes of obesity. Findings from addiction research seem very useful because there are certain similarities between addiction and obesity in terms of neurobiological causes. An improved understanding of the disease of obesity could help to develop more effective therapies for obese patients in the future. Further research, e. g. in the field of stress regulation, is thus urgently needed. PMID- 27005735 TI - [Abdominal pain, constipation and anemia]. AB - We present the case of a 42-year old man who went to the emergency department because of spasmodic abdominal pain. The abdomen was soft. A gastroscopy and a colonoscopy were without pathological findings. The laboratory analyses indicated anemia. The differential blood count showed basophilic granules in the red blood cells. The blood lead level was elevated. A lead poisoning was diagnosed. The cause was the oral intake of an ayurvedic medication which the patient had received in Bangladesh to treat his vitiligo. PMID- 27005736 TI - [Masked hypertension. Where to look?]. PMID- 27005737 TI - [Not Available]. PMID- 27005738 TI - [Not Available]. PMID- 27005740 TI - [CME - Rheumatology 8. Joint pain in nicotine use?]. PMID- 27005742 TI - Use of mobile and passive badge air monitoring data for NOX and ozone air pollution spatial exposure prediction models. AB - Air pollution exposure prediction models can make use of many types of air monitoring data. Fixed location passive samples typically measure concentrations averaged over several days to weeks. Mobile monitoring data can generate near continuous concentration measurements. It is not known whether mobile monitoring data are suitable for generating well-performing exposure prediction models or how they compare with other types of monitoring data in generating exposure models. Measurements from fixed site passive samplers and mobile monitoring platform were made over a 2-week period in Baltimore in the summer and winter months in 2012. Performance of exposure prediction models for long-term nitrogen oxides (NOX) and ozone (O3) concentrations were compared using a state-of-the-art approach for model development based on land use regression (LUR) and geostatistical smoothing. Model performance was evaluated using leave-one-out cross-validation (LOOCV). Models performed well using the mobile peak traffic monitoring data for both NOX and O3, with LOOCV R2s of 0.70 and 0.71, respectively, in the summer, and 0.90 and 0.58, respectively, in the winter. Models using 2-week passive samples for NOX had LOOCV R2s of 0.60 and 0.65 in the summer and winter months, respectively. The passive badge sampling data were not adequate for developing models for O3. Mobile air monitoring data can be used to successfully build well-performing LUR exposure prediction models for NOX and O3 and are a better source of data for these models than 2-week passive badge data. PMID- 27005743 TI - Trends in cell phone use among children in the Danish national birth cohort at ages 7 and 11 years. AB - We prospectively examined trends in cell phone use among children in the Danish National Birth Cohort. Cell phone use was assessed at ages 7 and 11 years, and we examined use patterns by age, by year of birth, and in relation to specific individual characteristics. There was an increase in cell phone use from age 7 (37%) to 11 years (94%). There was a clear pattern of greater reported cell phone use among children at age 7 years with later birth year, but this trend disappeared at age 11. Girls and those who used phones at age 7 talked more often and for longer durations at age 11 years. Low socio-economic status and later year of birth were associated with voice calls at age 7 but not at age 11 years. At age 11 most used cell phones for texting and gaming more than for voice calls. Further, children who started using cell phones at age 7 years were more likely to be heavy cell phone voice users at age 11 years, making early use a marker for higher cumulative exposure regardless of year of birth. As cell phone technology continues to advance, new use patterns will continue to emerge, and exposure assessment research among children must reflect these trends. PMID- 27005744 TI - Climate change impacts on projections of excess mortality at 2030 using spatially varying ozone-temperature risk surfaces. AB - We project the change in ozone-related mortality burden attributable to changes in climate between a historical (1995-2005) and near-future (2025-2035) time period while incorporating a non-linear and synergistic effect of ozone and temperature on mortality. We simulate air quality from climate projections varying only biogenic emissions and holding anthropogenic emissions constant, thus attributing changes in ozone only to changes in climate and independent of changes in air pollutant emissions. We estimate non-linear, spatially varying, ozone-temperature risk surfaces for 94 US urban areas using observed data. Using the risk surfaces and climate projections we estimate daily mortality attributable to ozone exceeding 40 p.p.b. (moderate level) and 75 p.p.b. (US ozone NAAQS) for each time period. The average increases in city-specific median April-October ozone and temperature between time periods are 1.02 p.p.b. and 1.94 degrees F; however, the results varied by region. Increases in ozone because of climate change result in an increase in ozone mortality burden. Mortality attributed to ozone exceeding 40 p.p.b. increases by 7.7% (1.6-14.2%). Mortality attributed to ozone exceeding 75 p.p.b. increases by 14.2% (1.6 28.9%). The absolute increase in excess ozone mortality is larger for changes in moderate ozone levels, reflecting the larger number of days with moderate ozone levels. PMID- 27005745 TI - Statin-related myotoxicity. AB - Statin therapy has a very important role in decreasing cardiovascular risk, and treatment non-compliance may therefore be a concern in high cardiovascular risk patients. Myotoxicity is a frequent side effect of statin therapy and one of the main causes of statin discontinuation, which limits effective treatment of patients at risk of or with cardiovascular disease. Because of the high proportion of patients on statin treatment and the frequency of statin-related myotoxicity, this is a subject of concern in clinical practice. However, statin related myotoxicity is probably underestimated because there is not a gold standard definition, and its diagnosis is challenging. Moreover, information about pathophysiology and optimal therapeutic options is scarce. Therefore, this paper reviews the knowledge about the definition, pathophysiology and predisposing conditions, diagnosis and management of statin-related myotoxicity, and provides a practical scheme for its management in clinical practice. PMID- 27005746 TI - Effects of dietary Tenebrio molitor meal inclusion in free-range chickens. AB - Insects are currently being considered as a novel protein source for animal feeds, because they contain a large amount of protein. The larvae of Tenebrio molitor (TM) have been shown to be an acceptable protein source for broiler chickens in terms of growth performance, but till now, no data on histological or intestinal morphometric features have been reported. This study has had the aim of evaluating the effects of dietary TM inclusion on the performance, welfare, intestinal morphology and histological features of free-range chickens. A total of 140 medium-growing hybrid female chickens were free-range reared and randomly allotted to two dietary treatments: (i) a control group and (ii) a TM group, in which TM meal was included at 75 g/kg. Each group consisted of five pens as replicates, with 14 chicks per pen. Growth performance, haematological and serum parameters and welfare indicators were evaluated, and the animals were slaughtered at the age of 97 days. Two birds per pen (10 birds/treatment) were submitted to histological (liver, spleen, thymus, bursa of Fabricius, kidney, heart, glandular stomach and gut) and morphometric (duodenum, jejunum and ileum) investigations. The inclusion of TM did not affect the growth performance, haematological or serum parameters. The morphometric and histological features were not significantly affected either, thus suggesting no influence on nutrient metabolization, performance or animal health. Glandular stomach alterations (chronic flogosis with epithelial squamous metaplasia) were considered paraphysiological in relation to free-range farming. The observed chronic intestinal flogosis, with concomitant activation of the lymphoid tissue, was probably due to previous parasitic infections, which are very frequently detected in free-range chickens. In conclusion, the findings of this study show that yellow mealworm inclusion does not affect the welfare, productive performances or morphological features of free-range chickens, thus confirming that TM can be used safely in poultry diets. PMID- 27005747 TI - Enrichment and determination of polybrominated diphenyl ethers in environmental water samples by magnetic solid-phase extraction with core-shell magnetic carbon microspheres before gas chromatography with mass spectrometry. AB - Core-shell magnetic carbon microspheres were synthesized by a simple hydrothermal method and used as a novel magnetic solid-phase extraction adsorbent for the sensitive determination of polybrominated diphenyl ethers in environmental water samples. Gas chromatography with negative chemical ionization mass spectrometry was adopted for the detection. Box-Behnken design was used to investigate and optimize important magnetic solid-phase extraction parameters through response surface methodology. Under the optimal conditions, low limits of detection (0.07 0.17 ng.L(-1) ), a wide linear range (1-1000 ng.L(-1) ), and good repeatability (0.80-4.58%) were achieved. The developed method was validated with several real water samples, and satisfactory results were obtained in the range of 72.8-97.9%. These results indicated that core-shell magnetic carbon microspheres have great potential as an adsorbent for the magnetic solid-phase extraction of polybrominated diphenyl ethers at trace levels from environmental water samples. PMID- 27005748 TI - Product-Derived Bimetallic Palladium Complex Catalyzes Direct Carbonylation of Sulfonylazides. AB - A novel product-derived bimetallic palladium complex catalyzes a sulfonylazide transfer reaction with the sigma-donor/pi-acceptor ligand CO, and is advantageous given its broad substrate scope, high efficiency, and mild reaction conditions (atmospheric pressure of CO at room temperature). This methodology provides a new approach to sulfonylureas, which are present in both pharmaceuticals and agrochemicals. The synthesis of Glibenclamide on a gram scale further revealed the practical utility of this procedure. Mechanistically, the generation of a bridged bimetallic palladium species derived from the product sulfonylurea is disclosed as the crucial step for this catalytic cycle. PMID- 27005750 TI - Factors associated with loss to follow-up among women in Option B+ PMTCT programme in northeast Ethiopia: a retrospective cohort study. AB - INTRODUCTION: Ethiopia has recently adopted lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women (Option B+ strategy), regardless of CD4 count or clinical stage. However, the exact timing and predictors of loss to follow-up (LFU) are unknown. Thus, we examined the levels and determinants of LFU under Option B+ among pregnant and breastfeeding women initiated on lifelong ART for prevention of mother-to-child transmission (PMTCT) in Ethiopia. METHODS: We conducted a retrospective cohort study among 346 pregnant and breastfeeding women who started ART at 14 public health facilities in northeast Ethiopia from March 2013 to April 2015. We defined LFU as 90 days since the last clinic visit among those not known to have died or transferred out. We used Kaplan-Meier and Cox proportional hazards regression to estimate cumulative LFU and identify the predictors of LFU, respectively. RESULTS: Of the 346 women included, 88.4% were pregnant and the median follow-up was 13.7 months. Overall, 57 (16.5%) women were LFU. The cumulative proportions of LFU at 6, 12 and 24 months were 11.9, 15.7 and 22.6%, respectively. The risk of LFU was higher in younger women (adjusted hazard ratio (aHR) 18 to 24 years/30 to 40 years: 2.3; 95% confidence interval (CI): 1.2 to 4.5), in those attending hospitals compared to those attending health centres (aHR: 1.8; 95% CI: 1.1 to 3.2), in patients starting ART on the same day of diagnosis (aHR: 1.85; 95% CI: 1.1 to 3.2) and missing CD4 cell counts at ART initiation (aHR: 2.3; 95% CI: 1.2 to 4.4). CONCLUSIONS: The level of LFU we found in this study is comparable with previous findings from other resource-limited settings. However, high early LFU shortly after ART initiation is still a major problem. LFU was high among younger women, those initiating ART on the day of HIV diagnosis, those missing baseline CD4 count and those attending hospitals. Thus, targeted HIV care and treatment programmes for these patients should be part of future interventions to improve retention in care under the Option B+ PMTCT programme. PMID- 27005749 TI - Effects of Long-Term Flutamide Treatment During Development on Sexual Behaviour and Hormone Responsiveness in Rams. AB - Testosterone exposure during midgestation differentiates neural circuits controlling sex-specific behaviours and patterns of gonadotrophin secretion in male sheep. Testosterone acts through androgen receptors (AR) and/or after aromatisation to oestradiol and binding to oestrogen receptors. The present study assessed the role of AR activation in male sexual differentiation. We compared rams that were exposed to the AR antagonist flutamide (Flu) throughout the critical period (i.e. days 30-90 of gestation) to control rams and ewes that received no prenatal treatments. The external genitalia of all Flu rams were phenotypically female. Testes were positioned s.c. in the inguinal region of the abdomen, exhibited seasonally impaired androgen secretion and were azospermic. Flu rams displayed male-typical precopulatory and mounting behaviours but could not intromit or ejaculate because they lacked a penis. Flu rams exhibited greater mounting behaviour than control rams and, similar to controls, showed sexual partner preferences for oestrous ewes. Neither control, nor Flu rams responded to oestradiol treatments with displays of female-typical receptive behaviour or LH surge responses, whereas all control ewes responded as expected. The ovine sexually dimorphic nucleus in Flu rams was intermediate in volume between control rams and ewes and significantly different from both. These results indicate that prenatal anti-androgen exposure is not able to block male sexual differentiation in sheep and suggest that compensatory mechanisms intervene to maintain sufficient androgen stimulation during development. PMID- 27005751 TI - Poorer limb salvage in African American men with chronic limb ischemia is due to advanced clinical stage and higher anatomic complexity at presentation. AB - OBJECTIVE: African Americans (AAs) with symptomatic peripheral arterial disease (PAD) have been reported to have fewer revascularization attempts and poorer patency and limb salvage (LS) rates than Caucasians (CAUs). This study compared the outcomes between AA and CAU men with chronic limb ischemia. METHODS: All AA and CAU men who underwent treatment for symptomatic PAD between November 1, 2003, and May 31, 2012, were included. Patency rates, LS, major adverse cardiovascular and limb events, amputation-free survival, and survival were compared before and after propensity score matching and with multivariate (Cox regression) analysis. RESULTS: Of the 834 men (1062 limbs), 107 were AA (137 limbs) and 727 were CAU (925 limbs). AAs were more likely to have insulin-dependent diabetes mellitus, hypertension, dialysis dependence, lower albumin levels, and critical limb ischemia (73% vs 61%; P = .006), whereas CAUs had more coronary artery disease, dyslipidemia, and chronic obstructive pulmonary disease. In patients with critical limb ischemia, primary amputation rates (10.9% vs 7.2%; P = .209) were similar between groups; however, infrapopliteal interventions were more frequent in AAs (62.6% vs 44.3%; P = .004). Perioperative morbidity and mortality rates were similar. Mean follow-up was 38.5 +/- 28.9 months (range, 0-119 months). Patency rates, major adverse limb and cardiovascular events, amputation-free survival, and survival were similar in AAs and CAUs; however, the LS rate was significantly lower in AA (73% +/- 6% vs 83% +/- 2%; P = .048), mainly due to the difference in the endovascular-treated group (5-year LS, 69% +/- 7% in AAs vs 84% +/- 2% in CAUs; P = .025). All outcomes were similar in propensity score-matched cohorts. In multivariate analysis, insulin-dependent diabetes mellitus, gangrene, poor functional capacity, dialysis-dependence, and need for infrapopliteal revascularization were independently associated with limb loss, whereas race was not. CONCLUSIONS: AA men with symptomatic PAD were found to have lower LS rates than CAUs. However, this was likely due to presenting with advanced ischemia or with poor prognostic factors that are independently associated with limb loss. PMID- 27005752 TI - Transient postoperative atrial fibrillation after abdominal aortic aneurysm repair increases mortality risk. AB - OBJECTIVE: The purpose of this study was to determine whether new-onset transient postoperative atrial fibrillation (TPAF) affects mortality rates after abdominal aortic aneurysm (AAA) repair and to identify predictors for the development of TPAF. METHODS: Patients who underwent open aortic repair or endovascular aortic repair for a principal diagnosis AAA were retrospectively identified using the Healthcare Cost and Utilization Project-State Inpatient Database (Florida) for 2007 to 2011 and monitored longitudinally for 1 year. Inpatient and 1-year mortality rates were compared between those with and without TPAF. TPAF was defined as new-onset atrial fibrillation that developed in the postoperative period and subsequently resolved in patients without a history of atrial fibrillation. Cox proportional hazards models, adjusted for age, gender, comorbidities, rupture status, and repair method, were used to assess 1-year survival. Predictive models were built with preoperative patient factors using Chi-squared Automatic Interaction Detector decision trees and externally validated on patients from California. RESULTS: A 3.7% incidence of TPAF was identified among 15,148 patients who underwent AAA repair. The overall mortality rate was 4.3%. The inpatient mortality rate was 12.3% in patients with TPAF vs 4.0% in those without TPAF. In the ruptured setting, the difference in mortality was similar between groups (33.7% vs 39.9%, P = .3). After controlling for age, gender, comorbid disease severity, urgency (ruptured vs nonruptured), and repair method, TPAF was associated with increased 1-year postoperative mortality (hazard ratio, 1.48; P < .001) and postdischarge mortality (hazard ratio, 1.56; P = .028). Chi-squared Automatic Interaction Detector-based models (C statistic = 0.70) were integrated into a Web-based application to predict an individual's probability of developing TPAF at the point of care. CONCLUSIONS: The development of TPAF is associated with an increased risk of mortality in patients undergoing repair of nonruptured AAA. Predictive modeling can be used to identify those patients at highest risk for developing TPAF and guide interventions to improve outcomes. PMID- 27005754 TI - Management of concomitant abdominal aortic aneurysm and colorectal cancer. AB - OBJECTIVE: To conduct a systematic review of the literature and perform an analysis of outcomes of treatment of concomitant colorectal cancer (CRC) and abdominal aortic aneurysm (AAA) with a focus on the different treatment options and the related therapeutic outcomes. METHODS: A review of the English-language medical literature from 1980 to 2015 was undertaken using the PubMed and EMBASE databases to identify studies reporting surgical treatment of patients with concomitant CRC and AAA. The search identified 24 articles encompassing 254 patients (81% male; mean age 73.5 +/- 6.1 years). RESULTS: In 96 patients (37.9%) cancer resection was performed first, followed by AAA repair at a later stage (open aortic repair [OAR], 79.2%; endovascular abdominal aortic repair [EVAR], 20.8%). Eighty-two patients (32.3%) underwent AAA repair (OAR, 47.5%; EVAR, 52.5%) before CRC resection. Seventy-one patients (27.9%) underwent combined OAR and CRC resection, and just five (1.9%) were treated with EVAR and cancer surgery in a single stage. There were eight of 96 interval AAA ruptures (8.3%), mostly in the early postoperative period concerning aneurysms >6 cm in diameter. The mean interval between the two procedures was much shorter in patients treated with EVAR than OAR (11.5 +/- 1.8 days vs 103.9 +/- 42.3 days). The overall 30-day mortality rate was 10.9%. Data from observational studies showed no significant differences in 30-day mortality between patients treated in one or two stages (P = .89). No mortality was recorded in any of the EVAR-treated patients. There was only one graft infection recorded (0.4%). CONCLUSIONS: Among different approaches, no significant differences in 30-day outcomes among patients treated in either two or one stage were evident. EVAR showed the lowest mortality and also diminished the delay between the two procedures in <2 weeks for a two-stage approach, although it has been associated with a significant risk for thrombotic events. The coexistence of AAA and CRC seems to favor the use of EVAR in treating those patients. PMID- 27005753 TI - Endoscopic vein harvest does not negatively affect patency of great saphenous vein lower extremity bypass. AB - OBJECTIVE: Although endoscopic vein harvest (EVH) has been reported to reduce the morbidity and length of stay compared with open vein harvest (OVH) for infrainguinal bypass procedures, there have been concerns about decreased graft patency and increased rates of reinterventions with EVH compared with OVH. We started using EVH in 2008, and currently it is our preferred approach. The goal of this study was to see if EVH is comparable to OVH in terms of graft patency and limb salvage and associated with fewer wound complications. METHODS: The study included 153 patients undergoing 171 elective lower extremity bypass procedures with single-piece autologous great saphenous vein from June 1, 2001, to December 31, 2014. Patients were observed postoperatively clinically and with duplex ultrasound evaluation. Patency, limb salvage rates, and postoperative complications were compared between OVH and EVH. RESULTS: There were 78 patients who had 88 EVH conduits and 75 patients who had 83 OVH conduits; 78.2% of the EVH group and 80% of the OVH group had critical limb ischemia (P = .237). Comorbidities were similar, but the EVH group had a significantly higher number of patients receiving antiplatelet drugs, enteric-coated acetylsalicylic acid (94.9% vs 70.7%; P < .001), and clopidogrel (62.8% vs 44%; P = .02), whereas the OVH group had more patients receiving warfarin anticoagulation (33.3% vs 20.5%; P = .073). Mean vein diameter was not signifciantly different (EVH, 3.2 +/- 0.7 mm; OVH, 3.2 +/- 0.8 mm; P = .598). Wound complication rates were significantly higher in the OVH group (EVH, 13.6%; OVH, 43.4%; P < .001), with 4.5% of patients in the EVH group and 18.1% of patients in the OVH group requiring debridement for wound complications (P = .005). Mean length of stay was shorter in the EVH group (EVH, 7.5 +/- 6.4 days; OVH, 9.6 +/- 11.0 days; P = .126). Early and late patency rates (EVH vs OVH 12- and 60-month primary patency, 73% +/- 5% and 64% +/- 6% vs 72% +/- 5% and 56% +/- 7 [P = .785]; assisted primary patency, 81% +/- 5% and 77% +/- 5% vs 81% +/- 5% and 70% +/- 6% [P = .731]; secondary patency, 87% +/- 4% and 85% +/- 4% vs 82% +/- 4% and 73% +/- 6% [P = .193]) and limb salvage rates (critical limb ischemia only, 12 and 60 months, 94% +/- 3% and 81% +/- 7% vs 83% +/- 5% and 81% +/- 5% [P = .400]) were similar between the groups. CONCLUSIONS: In experienced hands, EVH is associated with a significant decrease in wound complications with similar graft patency, reintervention rates, and limb salvage. PMID- 27005755 TI - Endovascular aneurysm repair simulation can lead to decreased fluoroscopy time and accurately delineate the proximal seal zone. AB - BACKGROUND: The use of simulators for endovascular aneurysm repair (EVAR) is not widespread. We examined whether simulation could improve procedural variables, including operative time and optimizing proximal seal. For the latter, we compared suprarenal vs infrarenal fixation endografts, right femoral vs left femoral main body access, and increasing angulation of the proximal aortic neck. METHODS: Computed tomography angiography was obtained from 18 patients who underwent EVAR at a single institution. Patient cases were uploaded to the ANGIO Mentor endovascular simulator (Simbionix, Cleveland, Ohio) allowing for three dimensional reconstruction and adapted for simulation with suprarenal fixation (Endurant II; Medtronic Inc, Minneapolis, Minn) and infrarenal fixation (C3; W. L. Gore & Associates Inc, Newark, Del) deployment systems. Three EVAR novices and three experienced surgeons performed 18 cases from each side with each device in randomized order (n = 72 simulations/participant). The cases were stratified into three groups according to the degree of infrarenal angulation: 0 degrees to 20 degrees , 21 degrees to 40 degrees , and 41 degrees to 66 degrees . Statistical analysis used paired t-test and one-way analysis of variance. RESULTS: Mean fluoroscopy time for participants decreased by 48.6% (P < .0001), and total procedure time decreased by 33.8% (P < .0001) when initial cases were compared with final cases. When stent deployment accuracy was evaluated across all cases, seal zone coverage in highly angulated aortic necks was significantly decreased. The infrarenal device resulted in mean aortic neck zone coverage of 91.9%, 89.4%, and 75.4% (P < .0001 by one-way analysis of variance), whereas the suprarenal device yielded 92.9%, 88.7%, and 71.5% (P < .0001) for the 0 degrees to 20 degrees , 21 degrees to 40 degrees , and 41 degrees to 66 degrees cases, respectively. Suprarenal fixation did not increase seal zone coverage. The side of femoral access for the main body did not influence proximal seal zone coverage regardless of infrarenal angulation. CONCLUSIONS: Simulation of EVAR leads to decreased fluoroscopy times for novice and experienced operators. Side of femoral access did not affect precision of proximal endograft landing. The angulated aortic neck leads to decreased proximal seal zone coverage regardless of infrarenal or suprarenal fixation devices. PMID- 27005756 TI - Outcomes after open infrainguinal bypass in patients with scleroderma. AB - BACKGROUND: There are limited reports of outcomes after infrainguinal bypass surgery in patients with scleroderma. This study evaluated the long-term outcome after lower extremity bypass in these patients. METHODS: The study included all patients with systemic sclerosis who underwent infrainguinal bypass surgery for severe peripheral arterial disease at our institution from January 1, 2007, to August 31, 2014. Kaplan-Meier and Cox regression analyses were used to evaluate graft failure and limb salvage. These outcomes were compared with those of nonscleroderma patients who underwent infrainguinal bypass surgery during the same period. Outcomes were defined and evaluated by Society for Vascular Surgery standards. RESULTS: There were 18 autogenous grafts (6% femoral-popliteal, 11% femoral-tibial, 72% popliteal-tibial, 11% tibial-tibial) placed in 18 limbs from 12 patients with systemic sclerosis. Mean +/- standard deviation age was 71 +/- 9.5 years, and most of the patients were women (83%) and white (78%). All patients presented with critical limb ischemia. History of hypertension and coronary artery disease were 94% and 61%, respectively. All grafts used were autogenous, continuous, and harvested from the lower extremity (nonreversed great saphenous in 61% and reversed great saphenous in 39%). Mean follow-up duration was 2.3 +/- 1.6 years. Graft failure was significantly higher in scleroderma patients than in nonscleroderma patients who underwent bypass in the same study period (hazard ratio, 7.2; 95% confidence interval, 1.44-41.4; P = .02). The limb salvage rate was 72%. CONCLUSIONS: Long-term outcomes after open infrainguinal bypass surgery in scleroderma patients are significantly worse than those in nonscleroderma patients. Careful consideration of their inherently poor outcomes should be made when reaching a decision for revascularization. PMID- 27005757 TI - Sn/Be Sequentially co-doped Hematite Photoanodes for Enhanced Photoelectrochemical Water Oxidation: Effect of Be(2+) as co-dopant. AB - For ex-situ co-doping methods, sintering at high temperatures enables rapid diffusion of Sn(4+) and Be(2+) dopants into hematite (alpha-Fe2O3) lattices, without altering the nanorod morphology or damaging their crystallinity. Sn/Be co doping results in a remarkable enhancement in photocurrent (1.7 mA/cm(2)) compared to pristine alpha-Fe2O3 (0.7 mA/cm(2)), and Sn(4+) mono-doped alpha Fe2O3 photoanodes (1.0 mA/cm(2)). From first-principles calculations, we found that Sn(4+) doping induced a shallow donor level below the conduction band minimum, which does not contribute to increase electrical conductivity and photocurrent because of its localized nature. Additionally, Sn(4+)-doping induce local micro-strain and a decreased Fe-O bond ordering. When Be(2+) was co-doped with Sn(4+)-doped alpha-Fe2O3 photoanodes, the conduction band recovered its original state, without localized impurities peaks, also a reduction in micro strain and increased Fe-O bond ordering is observed. Also the sequence in which the ex-situ co-doping is carried out is very crucial, as Be/Sn co-doping sequence induces many under-coordinated O atoms resulting in a higher micro-strain and lower charge separation efficiency resulting undesired electron recombination. Here, we perform a detailed systematic characterization using XRD, FESEM, XPS and comprehensive electrochemical and photoelectrochemical studies, along with sophisticated synchrotron diffraction studies and extended X-ray absorption fine structure. PMID- 27005758 TI - Role of Neutrophil Gelatinase-associated Lipocalin in the Detection of Contrast induced Nephropathy in Patients Undergoing a Coronary Angiography. PMID- 27005759 TI - Heart Team Decision-making in Spain: Is There Room for Improvement? Response. PMID- 27005760 TI - The Longitudinal Childhood Obesity Study (ELOIN): Design, Participation and Characteristics of the Baseline Sample. PMID- 27005761 TI - Effective teaching of endoscopy: a qualitative study of the perceptions of gastroenterology fellows and attending gastroenterologists. AB - BACKGROUND: There is little information describing the perceptions of gastroenterology fellows and attending gastroenterologists of what constitutes effective teaching of endoscopy. We sought to identify common themes regarding endoscopy training methods and their impact among fellows and attendings. METHODS: Focus group exercises and surveys were conducted among fellows, about educational resources, teaching techniques and ways of improving the teaching of endoscopy. The fellows identified the 'best' teachers of endoscopy, who were interviewed regarding their training in endoscopy, their teaching methods, key points of information, and opinions on endoscopy curriculum. RESULTS: Nineteen fellows (68%) had attended the American Society for Gastrointestinal Endoscopy First Year Fellows' Endoscopy course and found it very helpful. Thirteen fellows(46%) had exposure to an endoscopy simulator, but their median duration of use was only 1 hour. Only two out of five fellowship programs used a formal endoscopic skill assessment tool and none of the programs had an endoscopy curriculum of which the fellows were aware. Fellows reported that they learned endoscopy best by performing procedures. They also volunteered that attending gastroenterologists used variable teaching methods, and might benefit from instruction on how to teach endoscopy. Ten attending gastroenterologists (77%) had received training in advanced procedures; none received formal training on teaching endoscopy: they all felt that such training would be beneficial. CONCLUSIONS: A standardized endoscopy curriculum may be beneficial to fellows, who prefer to learn endoscopy by performing procedures-but they want explicit and specific instruction. Both those attending and the fellows thought that formal instruction for attending gastroenterologists on how to teach endoscopy would be beneficial, indicating a role for a 'teach-the-teacher' curriculum. PMID- 27005762 TI - Naringin improves zidovudine- and stavudine-induced skeletal muscle complications in rats. AB - Chronic use of nucleoside reverse transcriptase inhibitors (NRTIs) in managing human immunodeficiency virus (HIV) infection has been associated with several complications. Available management options for these complications have yielded controversial results, thus the need to urgently find newer alternatives. Naringin, a plant-derived flavonoid, has been shown to possess antioxidant and antiapoptotic properties which can be exploited in managing NRTI-induced complications. This study therefore investigated the effects of naringin on some NRTI-induced complications. Forty-nine rats (200-250 g) were divided into seven groups and were orally treated with stavudine (d4T)-only, d4T + naringin, d4T + vitamin E, zidovudine (AZT)-only, AZT + naringin, AZT + vitamin E, and distilled water, respectively. Drugs were administered once daily for 56 days, and oral glucose tolerance tests conducted on day 54 of the experiments and rats were thereafter sacrificed on day 56 by halothane overdose. Plasma samples and the left gastrocnemius muscles were stored at -80 degrees C for further analysis. There was significant glucose intolerance, insulin resistance, oxidative stress, and apoptosis in the skeletal muscles of AZT- or d4T-only-treated rats. Naringin, however, significantly reduced fasting blood glucose and fasting plasma insulin concentrations, mitigated glucose intolerance, and insulin resistance in addition to reducing malondialdehyde and carbonyl protein concentrations when coadministered with either NRTIs. Furthermore, naringin improved antioxidant enzyme activities, reduced skeletal muscle BCL-2-associated X protein expression, and improved B-cell lymphoma-2 protein expression compared to AZT- or d4T-only treated rats. Naringin ameliorated AZT- and d4T-induced complications and therefore should be further investigated as a possible nutritional supplement in managing HIV infection. PMID- 27005763 TI - Effects of quercetin on methotrexate-induced nephrotoxicity in rats. AB - OBJECTIVE: This experimental study was conducted to elucidate the possible protective/therapeutic effects of quercetin against methotrexate (Mtx)-induced kidney toxicity with biochemical and histopathological studies. METHODS: Twenty four adult male rats were randomly divided into four groups, as follows: control group (saline intraperitoneally (i.p.), 9 days), Mtx group (20 mg/kg i.p., single dose), Mtx + quercetin group (50 mg/kg quercetin was orally administered 2 days before and 6 days after Mtx administration) and only quercetin group (50 mg/kg oral, 9 days). Structural changes were evaluated by hematoxylin-eosin and periodic acid-Schiff stainings. Apoptotic changes were investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and caspase-3 antibody. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured in tissue and plasma samples. RESULTS: Mtx compared with the control group, there was significant increase in nephrotoxic tissue damage findings, in addition to apoptotic index (APOI) and caspase-3 expression ( p < 0.05). Mtx + quercetin group revealed significantly lower histopathological damage and APOI and caspase 3 expression decreased when compared to Mtx group. MDA levels were increased in Mtx group compared to others, and by the use of quercetin, this increase was significantly reduced. SOD levels were higher in Mtx group than others. This increase was evaluated as a relative increase arising from oxidative damage caused by Mtx. CONCLUSION: As a result, Mtx administration may involve oxidative stress by causing structural and functional damage in kidney tissue in rats. Quercetin reduced the Mtx-induced oxidative stress through its antioxidant properties and so quercetin may be promising to alleviate Mtx-induced renal toxicity. PMID- 27005764 TI - A woman with abdominal distension and pain. PMID- 27005765 TI - The impact of mild peri-operative hypothermia on the effectiveness of tranexamic acid in total hip arthroplasty. AB - PURPOSE: Surgical patients experience inadvertent hypothermia as a result of anaesthesia-induced thermoregulatory impairment. Previous studies have found that hypothermia is associated with increased blood loss and transfusion requirements. This study examined the incidence of hypothermia in patients undergoing total hip arthroplasty (THA), whether hypothermia is associated with increased blood loss, and whether any such association is modified by tranexamic acid (TXA) administration. METHODS: An observational prospective study was performed in 941 consecutive patients undergoing elective THA, with and without intra-operative administration of TXA. The presence of hypothermia on post-anaesthesia care unit admission was determined, and the post-operative bleeding index calculated. Transfusions and complications were documented. RESULTS: The incidence of peri operative inadvertent hypothermia was 84.2 %. TXA was administered to 751 (79.8 %) patients. The bleeding index was 2.6 (95 % confidence interval [CI] 2.6-2.7) in patients treated with TXA and 3.1 (95 % CI 2.8-3.4) in patients who did not receive TXA (p = 0.012). Mild hypothermia did not have a significant impact on the bleeding index (difference, -0.4; 95 % CI, -1.1 to +0.2; p = 0.190), nor on the effectiveness of TXA (difference, 0.4; 95 % CI, -0.3 to +1.1; p = 0.250). CONCLUSION: The incidence of hypothermia in our THA population was high, despite peri-operative air warming. However, mild hypothermia was not significantly associated with increased blood loss and did not reduce the effectiveness of TXA. PMID- 27005766 TI - Tablet-Aided BehavioraL intervention EffecT on Self-management skills (TABLETS) for Diabetes. AB - BACKGROUND: Multiple randomized controlled trials (RCTs) show that behavioral lifestyle interventions are effective in improving diabetes management and that comprehensive risk factor management improves cardiovascular disease (CVD) outcomes. The role of technology has been gaining strong support as evidence builds of its potential to improve diabetes management; however, evaluation of its impact in minority populations is limited. This study intends to provide early evidence of a theory-driven intervention, Tablet-Aided BehavioraL intervention EffecT on Self-management skills (TABLETS), using real-time videoconferencing for education and skills training. We examine the potential for TABLETS to improve health risk behaviors and reduce CVD risk outcomes among a low income African American (AA) population with poorly controlled type 2 diabetes. METHODS: The study is a two-arm, pilot controlled trial that randomizes 30 participants to the TABLETS intervention and 30 participants to a usual care group. Blinded outcome assessments will be completed at baseline, 2.5 months (immediate post-intervention), and 6.5 months (follow-up). The TABLETS intervention consists of culturally tailored telephone-delivered diabetes education and skills training delivered via videoconferencing on tablet devices, with two booster sessions delivered via tablet-based videoconferencing at 3 months and 5 months to stimulate ongoing use of the tablet device with access to intervention materials via videoconferencing slides and a manual of supplementary materials. The primary outcomes are physical activity, diet, medication adherence, and self-monitoring behavior, whereas the secondary outcomes are HbA1c, low-density lipoprotein cholesterol (LDL-C), BP, CVD risk, and quality of life. DISCUSSION: This study provides a unique opportunity to assess the feasibility and efficacy of a theory-driven, tablet-aided behavioral intervention that utilizes real-time videoconferencing technology for education and skills training on self-management behaviors and quality of life among a high-risk, low income AA population with an uncontrolled dyad or triad of CVD risk factors (diabetes with or without hypertension or hyperlipidemia). The intervention leverages the use of novel technology for education and skill-building to foster improved diabetes self-management. The findings of this study will inform the process of disseminating the intervention to a broader and larger sample of people and can potentially be refined to align with clinical workflows that target a subsample of patients with poor diabetes self-management. TRIAL REGISTRATION: The trial was registered in April 2014 with the United States National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier NCT02128854), available online at: http://clinicaltrials.gov/ct2/show/NCT02128854 . PMID- 27005767 TI - Rapid and high-dose titration of epoprostenol improves pulmonary hemodynamics and clinical outcomes in patients with idiopathic and heritable pulmonary arterial hypertension. AB - BACKGROUND: Intravenous epoprostenol is an effective treatment for idiopathic and heritable pulmonary arterial hypertension. We aimed to clarify factors that determine the survival of patients with severe pulmonary hypertension who received epoprostenol treatment. METHODS: This is a retrospective observational study consisting of 46 patients with idiopathic and heritable pulmonary arterial hypertension in World Health Organization (WHO) functional class III or IV and undergoing intravenous epoprostenol treatment. We compared the following factors between survivors and non-survivors: clinical characteristics, exercise capacity, hemodynamics, interval between diagnosis and treatment initiation, concomitant pulmonary arterial hypertension-targeted drugs, maximum dose of epoprostenol, and the speed of up-titration. We defined a rapid increase group as those receiving epoprostenol >=20ng/kg/min at 3 months and >=45ng/kg/min at 1 year of treatment. RESULTS: Thirty-two patients (70%) survived and 14 patients died during an average follow-up period of 2100 days. Mean pulmonary artery pressure, concomitant pulmonary arterial hypertension-targeted drugs, and the maximum epoprostenol dose were comparable between the two subsets of patients. WHO functional class III was more common than class IV, and the 6-min walking distance was longer in the survivor than the non-survivor group. The survivors typically showed a rapid increase in epoprostenol dose during the first year of treatment. This rapid increase group was associated with a continuous reduction in mean pulmonary artery pressure during the follow-up period, whereas the slow increase group showed no reduction in mean pulmonary artery pressure after 6 months of treatment. The 9.5-year survival rate was also significantly better in the rapid increase group compared with the slow increase group (100% vs. 64%, p=0.022). CONCLUSIONS: In idiopathic and heritable pulmonary arterial hypertension patients, a rapid increase in epoprostenol dose soon after the initiation of treatment seems to be important to achieve a continuous reduction in mean pulmonary artery pressure and to improve survival. PMID- 27005768 TI - Rationale, design, and baseline characteristics of a study to evaluate the effect of febuxostat in preventing cerebral, cardiovascular, and renal events in patients with hyperuricemia. AB - BACKGROUND: Since uric acid is associated with cardiovascular and renal disease, a treatment to maintain blood uric acid level may be required in patients with hyperuricemia. This study aims to evaluate preventive effects of febuxostat, a selective xanthine oxidase inhibitor, on cerebral, cardiovascular, and renal events in patients with hyperuricemia compared to conventional treatment. METHODS AND RESULTS: This study is a prospective randomized open-label blinded endpoint study. Patient enrolment was started in November 2013 and was completed in October 2014. The patients will be followed for at least 3 years. The primary endpoint is a composite of cerebral, cardiovascular, and renal events, and all deaths including death due to cerebral, cardiovascular, and renal disease, new or recurring cerebrovascular disease, new or recurring non-fatal coronary artery disease, cardiac failure requiring hospitalization, arteriosclerotic disease requiring treatment, renal impairment, new atrial fibrillation, and all deaths other than cerebral or cardiovascular or renal disease. These events will be independently evaluated by the Event Assessment Committee under blinded information regarding the treatment group. The study was registered at ClinicalTrials.gov with the identifier NCT01984749. PMID- 27005769 TI - Encapsulation and release studies of strawberry polyphenols in biodegradable chitosan nanoformulation. AB - Polyphenols (negative groups) of strawberry extract interacts with positively protonated amino groups of chitosan which helps in maximum encapsulation. This approach can improve the bioavailability and sustained release of phytochemicals having lower bioavailability. The optimum mass ratio of chitosan-tripolyphosphate and polyphenols (PPs) loading was investigated to be 3:1 and 0.5mg/ml of strawberry extract, respectively. Prepared nanoformulation were characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy. The formed particles size ranged between 300 and 600nm and polydispersity index (PDI) of~0.5. The optimized formulation showed encapsulation efficiency of 58.09% at 36.47% of polyphenols loading. Initial burst and continuous release of PPs was observed at pH 7.4 of in vitro release studies. PPs release profile at this pH was found to be non-Fickian analomous diffusion and the release was followed first order kinetics. And at pH 1.4, diffusion controlled Fickian release of PPs was observed. PMID- 27005770 TI - Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database. AB - BACKGROUND: To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. METHODS: The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. RESULTS: In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). CONCLUSION: Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future. PMID- 27005771 TI - Rationing tests for drug-resistant tuberculosis - who are we prepared to miss? AB - BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority. PMID- 27005774 TI - Corrigendum: Organic Carbonates: Efficient Extraction Solvents for the Synthesis of HMF in Aqueous Media with Cerium Phosphates as Catalysts. PMID- 27005772 TI - Genetic diversity, linkage disequilibrium and power of a large grapevine (Vitis vinifera L) diversity panel newly designed for association studies. AB - BACKGROUND: As for many crops, new high-quality grapevine varieties requiring less pesticide and adapted to climate change are needed. In perennial species, breeding is a long process which can be speeded up by gaining knowledge about quantitative trait loci linked to agronomic traits variation. However, due to the long juvenile period of these species, establishing numerous highly recombinant populations for high resolution mapping is both costly and time-consuming. Genome wide association studies in germplasm panels is an alternative method of choice, since it allows identifying the main quantitative trait loci with high resolution by exploiting past recombination events between cultivars. Such studies require adequate panel design to represent most of the available genetic and phenotypic diversity. Assessing linkage disequilibrium extent and panel power is also needed to determine the marker density required for association studies. RESULTS: Starting from the largest grapevine collection worldwide maintained in Vassal (France), we designed a diversity panel of 279 cultivars with limited relatedness, reflecting the low structuration in three genetic pools resulting from different uses (table vs wine) and geographical origin (East vs West), and including the major founders of modern cultivars. With 20 simple sequence repeat markers and five quantitative traits, we showed that our panel adequately captured most of the genetic and phenotypic diversity existing within the entire Vassal collection. To assess linkage disequilibrium extent and panel power, we genotyped single nucleotide polymorphisms: 372 over four genomic regions and 129 distributed over the whole genome. Linkage disequilibrium, measured by correlation corrected for kinship, reached 0.2 for a physical distance between 9 and 458 Kb depending on genetic pool and genomic region, with varying size of linkage disequilibrium blocks. This panel achieved reasonable power to detect associations between traits with high broad-sense heritability (> 0.7) and causal loci with intermediate allelic frequency and strong effect (explaining > 10 % of total variance). CONCLUSIONS: Our association panel constitutes a new, highly valuable resource for genetic association studies in grapevine, and deserves dissemination to diverse field and greenhouse trials to gain more insight into the genetic control of many agronomic traits and their interaction with the environment. PMID- 27005775 TI - Corrigendum: Levulinic Acid Biorefineries: New Challenges for Efficient Utilization of Biomass. PMID- 27005776 TI - The stress response of human proximal tubule cells to cadmium involves up regulation of haemoxygenase 1 and metallothionein but not cytochrome P450 enzymes. AB - Enzymes of the cytochrome P450 (CYP) super-family are implicated in cadmium (Cd) induced nephrotoxicity, however, direct evidence is lacking. This study investigated the endogenous expression of various CYP proteins together with the stress-response proteins, heme oxygenase-1 (HO-1) and metallothionein (MT) in human kidney sections and in cadmium-exposed primary cultures of human proximal tubular epithelial cells (PTC). By immunohistochemistry, the CYP members 2B6, 4A11 and 4F2 were prominently expressed in the cortical proximal tubular cells and to a lesser extent in distal tubular cells. Low levels of CYPs 2E1 and 3A4 were also detected. In PTC, in the absence of Cd, CYP2E1, CYP3A4, CYP4F2 and MT were expressed, but HO-1, CYP2B6 and CYP4A11 were not detected. A range of cadmium concentrations (0-100MUM) were utilized to induce stress conditions. MT protein was further induced by as little as 0.5MUM cadmium, reaching a 6-fold induction at 20MUM, whereas for HO-1, a 5MUM cadmium concentration was required for initial induction and at 20MUM cadmium reached a 15-fold induction. The expression of CYP2E1, CYP3A4, and CYP4F2 were not altered by any cadmium concentrations tested at 48h. Cadmium caused a reduction in cell viability at concentrations above 10MUM. In conclusion although cultured PTC, do express CYP proteins, (CYP2E1, CYP3A4, and CYP4F2), Cd-induced cell stress as indicted by induction of HO-1 and MT does not alter expression of these CYP proteins at 48h. PMID- 27005777 TI - Methylation levels of P16 and TP53 that are involved in DNA strand breakage of 16HBE cells treated by hexavalent chromium. AB - The correlations between methylation levels of p16 and TP53 with DNA strand breakage treated by hexavalent chromium [Cr(VI)] remain unknown. In this research, Human bronchial epithelial cells (16HBE cells) in vitro and bioinformatics analysis were used to analyze the epigenetic role in DNA damage and potential biomarkers. CCK-8 and single cell gel electrophoresis assay were chosen to detect the cellular biological damage. MALDI-TOF-MS was used to detect the methylation levels of p16 and TP53. qRT-PCR was used to measure their expression levels in different Cr(VI) treatment groups. The transcription factors with target sequences of p16 and TP53 were predicted using various bioinformatics software. The findings showed that the cellular toxicity and DNA strand damage were Cr(VI) concentration dependent. The hypermethylation of CpG1, CpG31 and CpG32 of p16 was observed in Cr(VI) treated groups. There was significant positive correlation between the CpG1 methylation level of p16 and cell damage. In Cr(VI) treated groups, the expression level of p16 was lower than that in control group. The expression level of TP53 increased when the Cr(VI)concentration above 5MUM. About p16, there was significant negative correlation between the CpG1 methylation levels with its expression level. A lot of binding sites for transcription factors existed in our focused CpG islands of p16. All the results suggested that the CpG1 methylation level of p16 could be used as a biomarker of epigenetic effect caused by Cr(VI) treatment, which can enhance cell damage by regulating its expression or affecting some transcription factors to combine with their DNA strand sites. PMID- 27005779 TI - Large-Scale Functional RNAi Screen in C. elegans Identifies TGF-beta and Notch Signaling Pathways as Modifiers of CACNA1A. AB - Variants in CACNA1A that encodes the pore-forming alpha1-subunit of human voltage gated Cav2.1 (P/Q-type) Ca(2+)channels cause several autosomal-dominant neurologic disorders, including familial hemiplegic migraine type 1, episodic ataxia type 2, and spinocerebellar ataxia type 6. To identify modifiers of incoordination in movement disorders, we performed a large-scale functional RNAi screen, using the Caenorhabditis elegansstrain CB55, which carries a truncating mutation in the unc-2gene, the worm ortholog for the human CACNA1A The screen was carried out by the feeding method in 96-well liquid culture format, using the ORFeome v1.1 feeding library, and time-lapse imaging of worms in liquid culture was used to assess changes in thrashing behavior. We looked for genes that, when silenced, either ameliorated the slow and uncoordinated phenotype of unc-2, or interacted to produce a more severe phenotype. Of the 350 putative hits from the primary screen, 37 genes consistently showed reproducible results. At least 75% of these are specifically expressed in the C. elegansneurons. Functional network analysis and gene ontology revealed overrepresentation of genes involved in development, growth, locomotion, signal transduction, and vesicle-mediated transport. We have expanded the functional network of genes involved in neurodegeneration leading to cerebellar ataxia related to unc-2/CACNA1A, further confirming the involvement of the transforming growth factor beta pathway and adding a novel signaling cascade, the Notch pathway. PMID- 27005780 TI - A novel allele HLA-C*07:445 identified in a French hematopoietic stem cell donor. AB - The novel allele HLA-C*07:445 has 1 nucleotide change from HLA-C*07:01 at nucleotide 277 C>A in exon 2. PMID- 27005778 TI - Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. AB - Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive molecular profiling of circulating metabolites captures highly heritable traits, which can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide association study of genetic influences on 123 circulating metabolic traits quantified by nuclear magnetic resonance metabolomics from up to 24,925 individuals and identify eight novel loci for amino acids, pyruvate and fatty acids. The LPA locus link with cardiovascular risk exemplifies how detailed metabolic profiling may inform underlying aetiology via extensive associations with very-low-density lipoprotein and triglyceride metabolism. Genetic fine mapping and Mendelian randomization uncover wide-spread causal effects of lipoprotein(a) on overall lipoprotein metabolism and we assess potential pleiotropic consequences of genetically elevated lipoprotein(a) on diverse morbidities via electronic health care records. Our findings strengthen the argument for safe LPA-targeted intervention to reduce cardiovascular risk. PMID- 27005781 TI - High levels of circulating extracellular vesicles with altered expression and function during pregnancy. AB - Extracellular vesicles (EVs) are widely considered important modulators of cell cell communication and may interact with target cells locally and on a systemic level. Several studies had shown that circulating EVs' levels are increased during pregnancy. However, EVs characteristics, composition and biological functions in pregnancy still need to be clarified. This study aims to determine if circulating EVs during pregnancy are modified regarding levels, markers and cytokine profile as well as their reactivity towards peripheral blood cells. 26 pregnant women (PW) being in the second gestational trimester and 59 non-pregnant women (NPW) were investigated. EVs enrichment was performed by ExoQuickTM or ultracentrifugation; nanoparticle tracking analysis, SDS-PAGE followed by Western Blotting and densitometry, and IFN-gamma, IL-10 and TGF-beta1 ELISA for EVs characterization; imaging flow cytometry to analyze EVs' uptake by peripheral blood cells and flow cytometry were performed to analyze EVs function regarding induction of caspase-3 activity. Circulating EVs' levels were increased during pregnancy [26.9*10(6)EVs/ml (range: 6.4-46.3); p=0.003] vs NPW [18.9*10(6)EVs/ml (range: 2.5-61.3)]. Importantly, the immunosuppressive TGF-beta1 and IL-10 cytokine cargo were increased in EVs of PW even after normalization to 1 million EVs [TGF-beta1: 0.25pg/10(6)EVs (range: 0.0-2.0); p<0.0001] and [IL-10: 0.21pg/10(6)EVs (range: 0.0-16.8); p=0.006] vs NPW. Although EVs derived from non pregnant and pregnant women were taken up by NK cells, the latter exclusively enhanced the caspase-3 activity in CD56(dim) NK cells (8.2+/-0.9; p=0.02). The qualitative and quantitative pregnancy-related alterations of circulating EVs provide first hints for an immune modulating role of circulating EVs during pregnancy. PMID- 27005782 TI - A potent Nrf2 activator, dh404, bolsters antioxidant capacity in glial cells and attenuates ischaemic retinopathy. AB - An imbalance in oxidative stress and antioxidant defense mechanisms contributes to the development of ischaemic retinopathies such as diabetic retinopathy and retinopathy of prematurity (ROP). Currently, the therapeutic utility of targeting key transcription factors to restore this imbalance remains to be determined. We postulated that dh404, an activator of nuclear factor erythroid-2 related factor 2 (Nrf2), the master regulator of oxidative stress responses, would attenuate retinal vasculopathy by mechanisms involving protection against oxidative stress mediated damage to glia. Oxygen-induced retinopathy (OIR) was induced in neonatal C57BL/6J mice by exposure to hyperoxia (phase I) followed by room air (phase II). dh404 (1 mg/kg/every second day) reduced the vaso-obliteration of phase I OIR and neovascularization, vascular leakage and inflammation of phase II OIR. In phase I, the astrocytic template and vascular endothelial growth factor (VEGF) expression necessary for physiological angiogenesis are compromised resulting in vaso-obliteration. These events were attenuated by dh404 and related to dh404's ability to reduce the hyperoxia-induced increase in reactive oxygen species (ROS) and markers of cell damage as well as boost the Nrf2-responsive antioxidants in cultured astrocytes. In phase II, neovascularization and vascular leakage occurs following gliosis of Muller cells and their subsequent increased production of angiogenic factors. dh404 reduced Muller cell gliosis and vascular leakage in OIR as well as the hypoxia-induced increase in ROS and angiogenic factors with a concomitant increase in Nrf2-responsive antioxidants in cultured Muller cells. In conclusion, agents such as dh404 that reduce oxidative stress and promote antioxidant capacity offer a novel approach to lessen the vascular and glial cell damage that occurs in ischaemic retinopathies. PMID- 27005783 TI - Disclosure of HIV Status to Health Care Providers in the Netherlands: A Qualitative Study. AB - We qualitatively investigated perspectives on HIV disclosure to health care providers (HCP) by people living with HIV (PLWH). Perspectives varied across PLWH and between PLWH and HCP. Some PLWH felt they should always disclose so that HCP could take necessary precautions or because disclosure optimized care. Others felt that disclosure was not an obligation but a courtesy. Still others felt that disclosure was unnecessary as all HCP should apply universal precautions or because HIV status was not relevant to care. Most HCP claimed they should be informed about patients' HIV status as this would reduce occupational risk of infection and improve care. HCP also felt that disclosure concerns by PLWH were unnecessary given the HCP' duty of professional confidentiality. Some acknowledged that disclosure was not always necessary but still indicated wanting to be informed. Perspectives on HIV disclosure in health care settings differed substantially between PLWH and HCP. PMID- 27005784 TI - Anthropometric characteristics and evaluation of nutritional status amongst female brick field workers of the unorganized sectors of West Bengal, India. AB - The purpose of the study is to evaluate the body composition and hand grip strength as indirect measures of nutritional status of 162 female workers and the status of the serum oxidative stress enzymes of 35 female workers engaged in the manual brick making units of the unorganized sectors of West Bengal, India. Results show that the waist-hip ratio values (mean 0.79 vs. 0.83; p=0.0034) are significantly greater amongst the brick carriers than the moulders. The body density (mean 1067.0 vs. 1056.0kg/m(3); p<0.0001) is lower and the body fat % (mean 10.63% vs. 13.09%; p<0.0001) of the brick carriers is significantly higher. The hand grip strength (HGS) (horizontal) of the brick workers in right (mean 379.52 vs. 267.72N; p<0.0001) and left (mean 268.78 vs. 162.79N; p<0.0001) hands are significantly greater than the control group. The serum malondialdehyde level is significantly higher (mean 99.97 vs. 160.21nmol/mg of protein; p<0.0001) but the superoxide dismutase level (mean 6.71 vs. 3.34unit/mg of protein; p<0.0001), glutathione level (GSH) (mean 3.93 vs. 2.11MUg/mg of protein; p<0.0001) and glutathione-s-transferase (GST) activity (mean 5.4 vs. 2.73nmole/min/mg of protein; p<0.0001) are significantly lower than that of the control group. The indirect nutritional assessments have shown that the women are poorly nourished. The hand grip strength is quite high in both groups of workers but consecutively decreases with the passage of time. Reduced levels of GSH and GST indicate that there is a higher level of reactive oxygen species inducing oxidative stress in the body. The probable causes of this state might be the intake of less nutritious food, polluted environment, excess ambient temperature and improper workstation. PMID- 27005785 TI - Economic and environmental evaluation of nitrogen removal and recovery methods from wastewater. AB - The driver for waste-based economic growth is long-term strategic design, and a paradigm-shift from waste treatment to resource recovery. This study aims to use an integrated modelling approach to evaluate the holistic economic and environmental profiles of three alternative nitrogen removal and recovery methods integrated into wastewater treatment systems, including conventional nitrification-denitrification, Anammox, and the anaerobic ion exchange route, to provide insights into N recovery system designs which are key elements in building a sustainable circular economy. Our results suggest that ion exchange is a promising technology showing high N removal-recovery efficiency from municipal wastewater and delivering competitive sustainability scores. In comparison with the well-developed conventional route, ion exchange and Anammox are undergoing significant research and development; as highlighted in sensitivity analyses, there is considerable room for process design and optimisation of ion exchange systems to achieve economically and environmentally optimal performance. PMID- 27005786 TI - Anaerobic biorefinery: Current status, challenges, and opportunities. AB - Anaerobic digestion (AD) has been in use for many decades. To date, it has been primarily aimed at treating organic wastes, mainly manures and wastewater sludge, and industrial wastewaters. However, with the current advancements, a more open mind is required to look beyond these somewhat restricted original applications of AD. Biorefineries are such concepts, where multiple products including chemicals, fuels, polymers etc. are produced from organic feedstocks. The anaerobic biorefinery concept is now gaining increased attention, utilizing AD as the final disposal step. This review aims at evaluating the potential significance of anaerobic biorefineries, including types of feedstocks, uses for the produced energy, as well as sustainable applications of the generated residual digestate. A comprehensive analysis of various types of anaerobic biorefineries has been developed, including both large-scale and household level applications. Finally, future directives are highlighted showing how anaerobic biorefinery concept could impact the bioeconomy in the near future. PMID- 27005787 TI - Multi-pollutant treatment of crystalline cellulosic effluent: Function of dissolved oxygen on process control. AB - Treatment of crystalline cellulose based wastewater was carried out in periodic discontinuous batch reactor (PDBR). Specific influence of dissolved oxygen on treatment of crystalline cellulosic (CC) wastewater was evaluated in three different microenvironments such as aerobic, anoxic and anaerobic. PDBR-aerobic biosystem documented relatively higher substrate degradation [2.63kgCOD/m(3)-day (92%)] in comparison to PDBR-anoxic [2.12kgCOD/m(3)-day (71%)] and PDBR-anaerobic [1.81kgCOD/m(3)-day (63%)], which is in accordance with the observed DO levels. Similarly, multipollutants viz., phosphates and nitrates removal was observed to be higher in aerobic followed by anoxic and anaerobic operations. Higher nitrate removal in aerobic operation might be attributed to the efficient denitrification carried out by the biocatalyst, which utilizes both nitrates and oxygen as oxidizing agents. Multiscan spectral profiles depicted reduction in color intensity in all three microenvironments that correlated with the substrate degradation observed. Despite the high organic load, PDBR functioned well without exhibiting process inhibition. PMID- 27005788 TI - Impacts of trace element supplementation on the performance of anaerobic digestion process: A critical review. AB - This paper critically reviews the impacts of supplementing trace elements on the anaerobic digestion performance. The in-depth knowledge of trace elements as micronutrients and metalloenzyme components justifies trace element supplementation into the anaerobic digestion system. Most of the earlier studies reported that trace elements addition at (sub)optimum dosages had positive impacts mainly longer term on digester stability with greater organic matter degradation, low volatile fatty acids (VFA) concentration and higher biogas production. However, these positive impacts and element requirements are not fully understood, they are explained on a case to case basis because of the great variance of the anaerobic digestion operation. Iron (Fe), nickel (Ni) and cobalt (Co) are the most studied and desirable elements. The right combination of multi elements supplementation can have greater positive impact. This measure is highly recommended, especially for the mono-digestion of micronutrient-deficient substrates. The future research should consider the aspect of trace element bioavailability. PMID- 27005789 TI - Concomitant biohydrogen and poly-beta-hydroxybutyrate production from dark fermentation effluents by adapted Rhodobacter sphaeroides and mixed photofermentative cultures. AB - This work aimed at investigating concomitant production of biohydrogen and poly beta-hydroxybutyrate (PHB) by photofermentation (PF) using dark fermentation effluents (DFE). An adapted culture of Rhodobacter sphaeroides AV1b (pH 6.5, 24+/ 2 degrees C) achieved H2 and PHB yields of 256 (+/-2) NmLH2/g Chemical Oxygen Demand (COD) and 273.8mgPHB/gCOD (32.5+/-3% of the dry cells weight (DCW)), respectively. When a diluted (1:2) DFE medium was applied to the adapted pure and mixed photofermentative culture, the respective H2 yields were 164.0 (+/-12) and 71.3 (+/-6) NmLH2/gCOD and the PHB yields were 212.1 (+/-105.2) and 50.7 (+/-2.7) mgPHB/gCOD added, corresponding to 24 (+/-0.7) and 6.3 (+/-0) % DCW, respectively. The concomitant H2 and PHB production from the PF process gave a good DFE post treatment achieving up to 80% COD removal from the initial DFE. PMID- 27005790 TI - Atmospheric CO2 capture by algae: Negative carbon dioxide emission path. AB - Carbon dioxide is one of the most important greenhouse gas, which concentration increase in the atmosphere is associated to climate change and global warming. Besides CO2 capture in large emission point sources, the capture of this pollutant from atmosphere may be required due to significant contribution of diffuse sources. The technologies that remove CO2 from atmosphere (creating a negative balance of CO2) are called negative emission technologies. Bioenergy with Carbon Capture and Storage may play an important role for CO2 mitigation. It represents the combination of bioenergy production and carbon capture and storage, keeping carbon dioxide in geological reservoirs. Algae have a high potential as the source of biomass, as they present high photosynthetic efficiencies and high biomass yields. Their biomass has a wide range of applications, which can improve the economic viability of the process. Thus, this paper aims to assess the atmospheric CO2 capture by algal cultures. PMID- 27005791 TI - Simultaneous saccharification and fermentation (SSF) of jackfruit seed powder (JFSP) to l-lactic acid and to polylactide polymer. AB - A newly isolated amylolytic lactic acid bacterium, Streptococcus equinus, was used for the production of l-lactic acid from jackfruit seed powder (JFSP) by simultaneous saccharification and fermentation (SSF). After optimization of shake flask fermentation by a response surface box-behnken design, the maximum lactate titer was 109g/L from 200g/L jackfruit seed powder. Amberlite IRA67, a weak base resin, was used to recover pure lactic acid from fermented broth and subsequently used for the synthesis of polylactic acid by direct condensation polymerization method with a yield of 62%. PMID- 27005792 TI - Microbial biodegradation of proteinaceous tannery solid waste and production of a novel value added product - Metalloprotease. AB - In this study, animal fleshing (ANFL) was utilized as a substrate for the production of extracellular protease by Clostridium limosum through central composite rotatable design (CCRD) and response surface methodology (RSM). Optimum protease production of 433U/ml was achieved and the purified enzyme was identified as acidic metalloprotease, a monomeric protein. The molecular weight of the enzyme was 71kDa, whose activity was enhanced by bivalent metals such as Zn(2+) and Mg(2+). Scanning electron microscopy (SEM) examination also revealed the hydrolysis/microbial degradation of ANFL through protease activity in the anaerobic fermentation process. Simultaneous hydrolysis of ANFL and production of an enzyme with the potential for different industrial applications provide an attractive methodology for the disposal of tannery solid waste. PMID- 27005793 TI - Artificial neural network based modeling to evaluate methane yield from biogas in a laboratory-scale anaerobic bioreactor. AB - The performance of a laboratory-scale anaerobic bioreactor was investigated in the present study to determine methane (CH4) content in biogas yield from digestion of organic fraction of municipal solid waste (OFMSW). OFMSW consists of food waste, vegetable waste and yard trimming. An organic loading between 40 and 120kgVS/m(3) was applied in different runs of the bioreactor. The study was aimed to focus on the effects of various factors, such as pH, moisture content (MC), total volatile solids (TVS), volatile fatty acids (VFAs), and CH4 fraction on biogas production. OFMSW witnessed high CH4 yield as 346.65LCH4/kgVS added. A target of 60-70% of CH4 fraction in biogas was set as an optimized condition. The experimental results were statistically optimized by application of ANN model using free forward back propagation in MATLAB environment. PMID- 27005794 TI - Acute generalised exanthematous pustulosis due to amoxicillin-clavulanate. PMID- 27005795 TI - Anorexia nervosa: a mistaken diagnosis. AB - Eating disorders in the form of anorexia and bulimia are becoming increasingly common in young adults and children. Most of the patients are initially seen by their general practitioner (GP) and it may take several months before the facts are pieced together and an underlying eating disorder is identified. However, other medical conditions, albeit rare, should be considered when assessing these young adults as potentially missing them can lead to devastating consequences. This case highlights how a 15-year-old girl who presented to her GP with a history suggestive of an eating disorder and had a body mass index below the 0.4th centile, in fact had classical symptoms and clinical signs of primary adrenal failure, or Addison's disease. PMID- 27005796 TI - Chloroquine-induced bilateral anterior shoulder dislocation: a unique aetiology for a rare clinical problem. AB - Bilateral anterior shoulder dislocation is a rare clinical entity with few case reports and limited series published in the literature. Bilateral shoulder dislocations are rare and of them, most are posterior. We present a highly unusual case of bilateral, atraumatic, anterior shoulder dislocation with concomitant comminuted greater tuberosity fracture on the right side, secondary to seizure, in a patient without known epilepsy, induced by oral chloroquine medication. We demonstrate the treatment approach that led to a satisfactory clinical outcome, evidenced by radiological union, clinical assessment and Patient Reported Outcome Measure data, following non-operative management of both shoulders. The unusual mechanism for anterior shoulder dislocation, the asymmetric dislocation pattern and peculiar precipitant for the causative seizure all provide interesting learning points from this case. PMID- 27005797 TI - Embolic superior mesenteric artery (SMA) occlusion secondary to a cardiac sarcoma. AB - We present a case of embolic acute mesenteric ischaemia (AMI) secondary to an underlying cardiac sarcoma, an exceedingly rare presentation only reported twice before. A 46-year-old man presented to accident and emergency department during the night with severe abdominal pain and vomiting. An urgent CT angiograph demonstrated superior mesenteric artery (SMA) occlusion with ischaemic small bowel. Joint surgical effort from vascular and general surgeons successfully recanalised the SMA and a 20 cm segment of small bowel was resected. Postoperatively, an echocardiogram demonstrated a mass within the left atrium. After cardiothoracic resection, the mass was found to be a rare undifferentiated cardiac sarcoma. Further staining on the embolus retrieved from the SMA revealed scattered spindle cells with a similar immunohistochemistry profile to that of the resected cardiac sarcoma. The patient was subsequently discharged well on lifelong warfarin. PMID- 27005798 TI - Spontaneous hypoglycaemia in a patient with Graves' disease. AB - A 23-year-old man, on treatment for Graves' disease, presented to the emergency department, with 2 separate episodes of loss of consciousness. During the first episode, the initial serum glucose was 19 mg/mL, and 44 mg/dL during the second episode. The patient was non-diabetic, and had elevated blood insulin, C peptide and insulin antibody levels. His abdominal radiographic findings were normal. He was diagnosed with Hirata disease, and put on propylthiouracil as a replacement for carbimazole. Hypoglycaemia was managed with dextrose infusions and frequent meals. The patient's condition improved and he had no further episodes of hypoglycaemia during the follow-up period. PMID- 27005799 TI - Foot drop following closed reduction of a total hip replacement. AB - Sciatic nerve palsy has been well documented and reported, following primary and revision hip replacement. It can also occur following dislocation of hip replacement. The incidence of sciatic nerve palsy in dislocated hip replacement is <0.1%. However, new onset sciatic nerve palsy following a closed reduction of dislocated hip replacement is even rarer. We describe a case of sciatic nerve palsy from traction injury following closed reduction of a total hip replacement. PMID- 27005800 TI - [Efficacy and effectiveness of biologic therapy in inflammatory bowel disease. EFIFECT study]. AB - INTRODUCTION: Randomized controlled trials provide the best scientific evidence for the efficacy of biological drugs in inflammatory bowel disease (IBD). However, findings obtained from these trials might not be reproducible in clinical practice. This study aimed to estimate the percentage of patients with IBD treated with biologics who would have been eligible for randomized controlled trials, and to compare the theoretical efficacy of biological drugs with their effectiveness in clinical practice. METHODS: We performed a retrospective multicenter study in 375 patients with IBD treated with anti-TNF agents and followed-up for 1 year. The eligibility criteria for the trial were taken from the ACCENT, SONIC, ACT, CLASSIC and CHARM trials. Eligible patients were included in a second analysis to compare results in clinical practice versus those hypothetically obtained if the patient had been included in a trial. RESULTS: Only 45.6% of 375 patients would have been eligible for pivotal trials. One-year clinical benefit (remission or response) was similar for eligible and non eligible cohorts (68.4% vs. 68.6%, P=.608). The clinical benefit was greater for current clinical practice than for a hypothetical trial situation (68.4% vs. 44.4%, P<.001) in eligible patients. CONCLUSION: More than half of patients with IBD treated with biologic drugs would not be represented in pivotal trials. The effectiveness of anti-TNF drugs in clinical practice exceeds their theoretical efficacy. PMID- 27005801 TI - Magnetic resonance imaging for developing intramuscular formulations. PMID- 27005802 TI - Factors Associated With Recurrence of Advanced Colorectal Adenoma After Endoscopic Resection. AB - BACKGROUND & AIMS: Studies have identified risk factors for recurrence of advanced colorectal adenoma (ACA) after polypectomy, but the relative importance and interaction of these risk factors, and their potential impact on surveillance recommendations, are unclear. We aimed to develop a model to identify ACA features associated with risk of recurrence after polypectomy. METHODS: In a retrospective study, we collected data from 3360 patients who underwent colonoscopy with polypectomy at University of Foggia from 2004 through 2008 and identified 746 patients with 1017 ACAs. We performed recursive partitioning analysis to identify factors associated with recurrence of ACA within 3 years after polypectomy. RESULTS: Median ACA size was 16 mm (range, 8-34 mm) and median number was 1.5 (range, 1-2). Pedunculated, sessile, and nonpolypoid lesions accounted for 41.3%, 39.4%, and 19.3% of ACAs detected, respectively. Factors independently associated with local recurrence of ACA and metachronous distant polyps within 3 years after polypectomy included size and number of ACAs and grade of dysplasia. The recurrence rate was 4.2% in patients with a single ACA <=15 mm without high-grade dysplasia (HGD), 21.3% in patients with HGD <=15 mm, ACA without HGD >15 mm, or multiple ACAs without HGD <=15 mm, and 57.9% in patients with HGD >15 mm. CONCLUSIONS: In this retrospective analysis of 746 patients with ACA who underwent polypectomy and surveillance colonoscopy within 3 years, the recurrence rate was highest in those with HGD >=15 mm. These patients might benefit from more intensive surveillance, whereas patients with a single ACA without HGD <=15 mm are at lower risk for and could be considered for longer follow-up intervals. PMID- 27005803 TI - Speciated High-Density Lipoprotein Biogenesis and Functionality. AB - Plasma high-density lipoprotein cholesterol (HDL-C) concentration is a negative risk factor for atherosclerotic cardiovascular disease (CVD). Despite this, most attempts to raise plasma HDL-C concentrations in a cardioprotective way have failed. Recently, hypotheses about the atheroprotective effects of HDL have shifted away from quantity to quality, mostly HDL function in reverse cholesterol transport. Plasma HDL from CVD patients is a poorer acceptor of cellular cholesterol than plasma from healthy controls, independent of plasma HDL-C concentrations. The function of HDL is likely determined by two other factors, stability and composition. The kinetic instability of HDL, which varies according to subclass, is a likely determinant of its reactivity in response to many HDL modifying activities. HDL composition is also heterogeneous and variable; all HDL particles contain apo AI but only about two-thirds contain apo AII. This occurs despite the fact that apo AI and apo AII are hepatically secreted on separate HDL that later fuse in plasma. HDL also contains traces of other proteins, some of which have not yet been associated with HDL function. One minor HDL species are those that are secreted with intact signal peptides, which enhances their binding to HDL; these HDL have special properties that are independent of cholesterol transport. Here, we review and provide a perspective about what is currently known about speciated HDL biogenesis in the context of health and disease. PMID- 27005804 TI - Cardiorespiratory Fitness and Atherosclerosis: Recent Data and Future Directions. AB - Historically, the relationship between exercise and the cardiovascular system was viewed as unidirectional, with a disease resulting in exercise limitation and hazard. This article reviews and explores the bidirectional nature, delineating the effects, generally positive, on the cardiovascular system and atherosclerosis. Exercise augments eNOS, affects redox potential, and favorably affects mediators of atherosclerosis including lipids, glucose homeostasis, and inflammation. There are direct effects on the vasculature as well as indirect benefits related to exercise-induced changes in body composition and skeletal muscle. Application of aerobic exercise to specific populations is described, with the hope that this knowledge will move the science forward and improve individual patient outcome. PMID- 27005805 TI - Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta analysis. AB - Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging. PMID- 27005806 TI - Feasibility study of axillary reverse mapping for patients with clinically node negative breast cancer. AB - BACKGROUND: The axillary reverse mapping (ARM) procedure was developed to identify and preserve arm lymphatic drainage during axillary lymph node dissection (ALND), thereby theoretically reducing the incidence of arm lymphedema. However, the oncological safety of this procedure has not yet been determined. METHODS: Two hundred ninety-two patients with clinically negative nodes (cN0) underwent both sentinel lymph node (SLN) biopsy and ARM. SLN was identified by dye and gamma probe methods, and ARM nodes were identified using a fluorescence imaging system. If SLN was histologically positive, ALND was performed with removal of ARM nodes. Otherwise, identified ARM nodes were preserved unless they coincided with SLN. Postoperatively, SLN as well as ARM nodes were histologically examined with H&E staining. RESULTS: SLN was identified in 286 of 292 patients, and ARM nodes were identified in 90 patients. In 54 patients with positive SLN, SLN was the same as the ARM node in 19 patients (the concordance type), whereas it was not an ARM node in the remaining 35 patients (the separate type). Non-SLN and ARM node was not involved in 51 of 54 patients with positive SLN, while it was involved in 3 patients of the concordance type. CONCLUSIONS: When ARM nodes were involved in patients with cN0, these were most often the SLN-ARM nodes. Therefore, it may be concluded that ARM nodes that do not coincide with SLNs might be preserved during ALND in SLN-positive patients. PMID- 27005807 TI - pcaReduce: hierarchical clustering of single cell transcriptional profiles. AB - BACKGROUND: Advances in single cell genomics provide a way of routinely generating transcriptomics data at the single cell level. A frequent requirement of single cell expression analysis is the identification of novel patterns of heterogeneity across single cells that might explain complex cellular states or tissue composition. To date, classical statistical analysis tools have being routinely applied, but there is considerable scope for the development of novel statistical approaches that are better adapted to the challenges of inferring cellular hierarchies. RESULTS: We have developed a novel agglomerative clustering method that we call pcaReduce to generate a cell state hierarchy where each cluster branch is associated with a principal component of variation that can be used to differentiate two cell states. Using two real single cell datasets, we compared our approach to other commonly used statistical techniques, such as K means and hierarchical clustering. We found that pcaReduce was able to give more consistent clustering structures when compared to broad and detailed cell type labels. CONCLUSIONS: Our novel integration of principal components analysis and hierarchical clustering establishes a connection between the representation of the expression data and the number of cell types that can be discovered. In doing so we found that pcaReduce performs better than either technique in isolation in terms of characterising putative cell states. Our methodology is complimentary to other single cell clustering techniques and adds to a growing palette of single cell bioinformatics tools for profiling heterogeneous cell populations. PMID- 27005809 TI - Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit. AB - Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. PMID- 27005808 TI - Pulmonary immunity and durable protection induced by the ID93/GLA-SE vaccine candidate against the hyper-virulent Korean Beijing Mycobacterium tuberculosis strain K. AB - The majority of tuberculosis (TB) vaccine candidates advanced to clinical trials have been evaluated preclinically using laboratory-adapted strains. However, it has been proposed that challenge with clinical isolates in preclinical vaccine testing could provide further and more practical validation. Here, we tested the ID93/GLA-SE TB vaccine candidate against the clinical Mycobacterium tuberculosis (Mtb) strain K (Mtb K) belonging to the Beijing family, the most prevalent Mtb strain in South Korea. Mice immunized with ID93/GLA-SE exhibited a significant reduction in bacteria and reduced lung inflammation against Mtb K when compared to non-immunized controls. In addition, we analyzed the immune responses in the lungs of ID93/GLA-SE-immunized mice, and showed that ID93/GLA-SE was able to elicit sustained Th1-biased immune responses including antigen-specific multifunctional CD4(+) T cell co-producing IFN-gamma, TNF-alpha, and IL-2 as well as a high magnitude of IFN-gamma response for up to 10 weeks post-challenge. Notably, further investigation of T cell subsets in the lung following challenge showed remarkable generation of CD8(+) central memory T cells by ID93/GLA-SE immunization. Our findings showed that ID93/GLA-SE vaccine confers a high level of robust protection against the hypervirulent Mtb Beijing infection which was characterized by pulmonary Th1-polarized T-cell immune responses. These findings may also provide relevant information for potential utility of this vaccine candidate in East-Asian countries where the Beijing genotype is highly prevalent. PMID- 27005810 TI - Sterile inflammation induced by Carbopol elicits robust adaptive immune responses in the absence of pathogen-associated molecular patterns. AB - Carbopol is a polyanionic carbomer used in man for topical application and drug delivery purposes. However parenteral administration of Carbopol in animal models results in systemic adjuvant activity including strong pro-inflammatory type-1 T cell (Th1) polarization. Here we investigated potential pathways of immune activation by Carbopol by comparison with other well-characterized adjuvants. Carbopol administration triggered rapid and robust leukocyte recruitment, pro inflammatory cytokine secretion and antigen capture largely by inflammatory monocytes. The induction of antigen specific Th1 cells by Carbopol was found to occur via a non-canonical pathway, independent of MyD88/TRIF signaling and in the absence of pattern-recognition-receptor (PRR) activation typically associated with Th1/Ig2a induction. Using multispectral fluorescence imaging (Imagestream) and electron microscopy we demonstrated that phagocytic uptake of Carbopol particles followed by entry into the phagosomal/lysosomal pathway elicited conformational changes to the polymer and reactive oxygen species (ROS) production. We therefore conclude that Carbopol may mediate its adjuvant activity via novel mechanisms of antigen presenting cell activation and Th1 induction, leading to enhanced IgG2a responses independent of microbial pattern recognition. PMID- 27005811 TI - Reliability of a Fluorescence-aided Identification Technique (FIT) for detecting tooth-colored restorations: an ex vivo comparative study. AB - OBJECTIVE: The aim of the study was to compare the diagnostic predictive values of a Fluorescence-aided Identification Technique (FIT) with those of the conventional diagnostic method regarding the identification of resin composite restorations. MATERIALS AND METHODS: Twenty examiners, 10 students, and 10 dentists were asked to identify composite restorations in a full-mouth model using both the FIT (405-nm light source) and the conventional method in combination with a common diagnostic light source. Each dental examination was repeated three times to calculate inter-/intra-operator agreement, repeatability, and reproducibility using kappa statistics. Predictive values were calculated using a filling prevalence of 42 % and the sensitivity and specificity of each method. Pearson's test and the 99 % confidence interval (CI) were used for comparison. RESULTS: The sensitivity (97 %, CI 94-99 %) and specificity (100 %, CI 98-100 %) of the FIT were significantly higher than those of the conventional method (27 %, CI 21-31 %, and 65 %, CI 58-72 %, respectively). Consequently, the positive (100 %) and negative (98 %) predictive values of the FIT were significantly higher than those of the conventional method (35 and 55 %, respectively). As expressed by the kappa statistics, the repeatability (0.96) and reproducibility (0.95) of the FIT were significantly better than those of the conventional method (0.49, CI 0.42-0.56, and 0.34, CI 0.26-0.43, respectively). CONCLUSION: Compared to the conventional technique, the FIT was significantly more reliable as shown by higher sensitivity, specificity, repeatability, and reproducibility values. CLINICAL RELEVANCE: The FIT should be considered as a reliable and practicable alternative in contrast to the conventional method, which was hardly sufficient as a diagnostic procedure. PMID- 27005812 TI - Efficacy of non-surgical periodontal therapy in the management of chronic periodontitis among obese and non-obese patients: a systematic review and meta analysis. AB - OBJECTIVE: There is a controversy over the influence of obesity on the periodontal treatment outcome in patients with chronic periodontitis (CP). The aim of the present systematic review was to evaluate the efficacy of non-surgical periodontal therapy (NSPT) in the management of CP among obese and non-obese patients. MATERIALS AND METHODS: The addressed focused question was "What is the efficacy, of NSPT with respect to clinical, radiographic, biochemical, microbiological, and patient-centered outcomes in obese as compared to non-obese chronic periodontitis patients?" Databases were searched from 1977 up to and including December 2014 using relevant key indexing terms. Unpublished data, experimental studies, letters to the editor, review articles, case reports, and commentaries were excluded. Meta-analysis of three studies was performed. RESULTS: Five clinical studies were included. The total number of patients ranged between 30 and 260 individuals. The mean age of patients was between 42.5 and 48.8 years. In three studies, the clinical periodontal parameters (plaque index (PI), gingival bleeding index (GBI), periodontal pocket depth (PPD), and clinical attachment loss (CAL)) in obese and non-obese patients following NSPT was comparable. Meta-analysis of PPD and CAL among obese and non-obese subjects showed comparable outcomes (PPD P = 0.91, I (2) 67.36 %; CAL P = 0.87, I (2) 77.16 %). However, in three studies, NSPT resulted in a significantly better clinical periodontal outcome among non-obese subjects than obese subjects. The difference in the levels of serum pro-inflammatory cytokine levels (IL-1beta, IL 6, TNF-alpha, IFN-gamma, leptin, adiponectin, and CRP) among obese and non-obese patients following treatment for CP was inconsistent. CONCLUSION: It remains unclear whether NSPT has a significantly higher impact on the clinical periodontal outcomes in obese patients than in non-obese patients with chronic periodontitis, given that the number of selected studies was relatively low and the reported findings were inconsistent. CLINICAL RELEVANCE: Although the effect of obesity on the outcome of NSPT still remains unclear, nevertheless clinicians are prompted to manage obesity prior to and during periodontal treatment. PMID- 27005814 TI - Pain research using Veterans Health Administration electronic and administrative data sources. AB - Health services researchers are using Veterans Health Administration (VHA) electronic health record (EHR) data sources to examine the prevalence, treatment, and outcomes of pain among Veterans in VHA care. Little guidance currently exists on using these data; thus, findings may vary depending on the methods, data sources, and definitions used. We sought to identify current practices in order to provide guidance to future pain researchers. We conducted an anonymous survey of VHA-affiliated researchers participating in a monthly national pain research teleconference. Thirty-two researchers (89%) responded: 75% conducted pain focused research, 78% used pain intensity numeric rating screening scale (NRS) scores to identify pain, 41% used International Classification of Diseases-9th Revision codes, and 57% distinguished between chronic and acute pain using either NRS scores or pharmacy data. The NRS and pharmacy data were rated as the most valid pain data sources. Of respondents, 48% reported the EHR data sources were adequate for pain research, while 45% had published peer-reviewed articles based on the data. Despite limitations, VHA researchers are increasingly using EHR data for pain research, and several common methods were identified. More information on the performance characteristics of these data sources and definitions is needed. PMID- 27005813 TI - Ectopic pregnancy risk factors for ART patients undergoing the GnRH antagonist protocol: a retrospective study. AB - BACKGROUND: In-vitro fertilization is a known risk factor for ectopic pregnancies. We sought to establish the risk factors for ectopic pregnancy in GnRH antagonist cycles examining patient and stimulation parameters with an emphasis on ovulation trigger. METHODS: We conducted a retrospective, cohort study of 343 patients undergoing 380 assisted reproductive technology (ART) cycles with the GnRH antagonist protocol and achieving a clinical pregnancy from November 2010 through December 2015. RESULTS: Significant risk factors for ectopic pregnancy in the univariate analysis included prior Cesarean section (CS), endometriosis, mechanical factor infertility, longer stimulation, elevated estradiol and progesterone levels, GnRH agonist trigger, higher number of oocytes aspirated, and insemination technique. Independent risk factors for ectopic pregnancy in the multivariate analysis included GnRH agonist trigger, higher number of oocytes aspirated, insemination technique, and prior Cesarean section. CONCLUSION: Excessive ovarian response, IVF (as opposed to ICSI), prior Cesarean section and GnRH agonist trigger were found to be independent risk factors for ectopic pregnancy. Caution should be exercised before incorporating the GnRH agonist trigger for indications other than preventing OHSS. When excessive ovarian response leads to utilization of GnRH agonist trigger, strategies for preventing ectopic pregnancy, such as a freeze all policy or blastocyst transfer, should be considered. Further studies should elucidate whether adjusting the luteal support can reduce the ectopic pregnancy risk. PMID- 27005815 TI - Exploring the intentions of pharmacy students towards pharmacy ownership by using theory of planned behaviour. AB - OBJECTIVE: The objective of this study was to assess the association of the constructs of theory of planned behaviour (behavioural beliefs, normative beliefs, control beliefs) and demographic variables with the intentions of pharmacy students to become pharmacy owner. METHODS: A cross sectional study was conducted between October and November, 2014, using a pretested, self administered questionnaire delivered to a sample of 350 pharmacy students at a private university of Pakistan. Behavioural beliefs, normative beliefs and control beliefs were assessed on four point Likert scale of agreement. The scores were summed and dichotomized based on an arbitrary 50% cut-off score to assess positive and negative beliefs. Binary logistic regression was used to analyse the data. RESULTS: A total of 313 participants (89.4%) responded to the questionnaire. Participants' behavioural beliefs, normative beliefs and control beliefs were negative towards pharmacy ownership with the mean scores of 13.90 +/ 0.41 (score range: 6-24), 9.66 +/- 0.49 (score range: 4-16) and 16.88 +/- 0.40 (score range: 7-28) respectively. Professional year and family business were significantly associated with intentions of pharmacy students to own a pharmacy (p < 0.05). CONCLUSION: Behavioural beliefs, normative beliefs and control beliefs were negative towards pharmacy ownership. Implementation of entrepreneurship course in pharmacy school may transform the beliefs of pharmacy students towards pharmacy ownership. PMID- 27005816 TI - Clopidogrel and hip fractures, is it safe? A systematic review and meta-analysis. AB - BACKGROUND: Femoral neck fractures in the elderly make up a large proportion of Orthopaedic surgical admissions each year. Operating on patients with clopidogrel poses a challenge because of the risk of bleeding and the difficulty deciding the optimal timing of surgery. The aim of this systematic review is to examine the published evidence to establish a set of guidelines for approaching neck of femur patients who are on clopidogrel. METHODS: All comparative studies with an intervention group and a control group were considered. Data on patient blood transfusion exposures, units transfused, haemoglobin concentration and drop in haemoglobin were extracted and pooled using the fixed effects model. Heterogeneity of the intervention effect was assessed with the I (2) statistic. RESULTS: A total of 4219 studies were identified. After removal of duplicates and after exclusion criteria were applied, there were 14 studies to be included. All 14 were case series with controls. There was no significant heterogeneity amongst the studies. Pooled odds ratio for transfusion exposures was 1.24 (95 % confidence interval 0.91 to 1.71) however this was not statistically significant (p = 0.14). No significant mean differences were found for other primary outcome measures. CONCLUSIONS: On the available evidence, we recommend that these patients can be managed by normal protocols with early surgery. Operating early on patients on clopidogrel is safe and does not appear to confer any clinically significant bleeding risk. As reported in other studies, we believe clopidogrel, if possible, should not be withheld throughout the perioperative period due to increased risk of cardiovascular events associated with stopping clopidogrel. Care should be taken intraoperatively to minimise blood loss due to the increased potential for bleeding. TRIAL REGISTRATION: This systematic review and meta analysis has been registered on Research Registry on July 16, 2015. The Review Registry Unique Identifying Number is: reviewregistry61 . PMID- 27005818 TI - Functional characterization and transient expression manipulation of a new sesquiterpene synthase involved in beta-caryophyllene accumulation in Ocimum. AB - The genus Ocimum has a unique blend of diverse secondary metabolites, with major proportion of terpenoids including mono- and sesquiterpenes. Although, beta Caryophyllene, bicyclic sesquiterpene, is one of the major terpene found in Ocimum species and known to possess several biological activities, not much is known about its biosynthesis in Ocimum. Here, we describe isolation and characterization of beta-caryophyllene synthase gene from Ocimum kilimandscharicum Gurke (OkBCS- GenBank accession no. KP226502). The open reading frame of 1629 bp encoded a protein of 542 amino acids with molecular mass of 63.6 kDa and pI value of 5.66. The deduced amino acid sequence revealed 50-70% similarity with known sesquiterpene synthases from angiosperms. Recombinant OkBCS converted farnesyl diphosphate to beta-caryophyllene as a major product (94%) and 6% alpha-humulene. Expression variation of OkBCS well corroborated with beta caryophyllene levels in different tissues from five Ocimum species. OkBCS transcript revealed higher expression in leaves and flowers. Further, agro infiltration based transient expression manipulation with OkBCS over-expression and silencing confirmed its role in beta-caryophyllene biosynthesis. These findings may potentially be further utilized to improve plant defense against insect pests. PMID- 27005817 TI - Association between insulin receptor substrate-1 polymorphisms and high platelet reactivity with clopidogrel therapy in coronary artery disease patients with type 2 diabetes mellitus. AB - BACKGROUND: The mechanisms leading to the high on-treatment platelet reactivity in diabetes patients are not fully elucidated. The genetic factors may be associated with the diminished antiplatelet efficacy of dual antiplatelet therapy. We investigated the possible association between insulin receptor substrate-1 (IRS-1) polymorphisms and high platelet reactivity in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 674 CAD patients with T2DM were enrolled in this study. Platelet aggregation and platelet activation were assessed with light transmission aggregometry and flow cytometry analysis, respectively. Participants were divided into high platelet reactivity (HPR) group and non-HPR group according to their maximal platelet aggregation. Genotypes were identified by polymerase chain reaction and direct sequencing of genomic DNA. The association between IRS-1 genetic variants and platelet function was assessed. RESULTS: There were 233 participants in the HPR group and 441 participants in the non-HPR group. G allele frequencies of rs13431554 were 27.7 % for the HPR group and 18.6 % for the non-HPR group (p < 0.001). Adenosine diphosphate and arachidonic acid induced platelet aggregation were significantly higher in G allele carriers compared with non-carriers (56.8 +/- 16.2 vs 52.0 +/- 17.9 %, p < 0.01, 28.9 +/- 18.6 vs 25.2 +/- 17.8 %, p < 0.01, respectively). We observed that P-selectin expression and PAC-1 binding were higher in G allele carriers compared with non-carriers (40.8 +/- 12.4 vs 36.2 +/- 13.8, p = 0.01; 43.7 +/- 15.9 vs 38.7 +/- 19.9, p = 0.03, respectively). CONCLUSION: The G allele of rs13431554 in the IRS-1 gene was associated with a hyperreactive platelet phenotype in the CAD patients with T2DM. PMID- 27005819 TI - Impact of simulated microgravity on human bone stem cells: New hints for space medicine. AB - Bone loss is a well known early event in astronauts and represents one of the major obstacle to space exploration. While an imbalance between osteoblast and osteoclast activity has been described, less is known about the behavior of bone mesenchymal stem cells in microgravity. We simulated microgravity using the Random Positioning Machine and found that mesenchymal stem cells respond to gravitational unloading by upregulating HSP60, HSP70, cyclooxygenase 2 and superoxyde dismutase 2. Such an adaptive response might be involved in inducing the overexpression of some osteogenic transcripts, even though the threshold to induce the formation of bone crystal is not achieved. Indeed, only the addition of an osteogenic cocktail activates the full differentiation process both in simulated microgravity and under static 1G-conditions. We conclude that simulated microgravity alone reprograms bone mesenchymal stem cells towards an osteogenic phenotype which results in complete differentiation only after exposure to a specific stimulus. PMID- 27005820 TI - Identification and characterization of an endoplasmic reticulum localization motif. AB - Sorting motifs are involved in the transport of diverse proteins. In the present study, we identified a hydrophobic peptide (WRPWRNFWWSIRVPWRRN) that was able to target enhanced green fluorescent protein- or DsRed2-enriched vesicular-like sub compartments of the endoplasmic reticulum (ER). Analysis of mutation constructs revealed that the sequence WRPWRNFWW was responsible for the ER-targeting activity, and the arginine residue of the peptide is a critical determinant of ER localization. Results from co-immunoprecipitation, glutathione S-transferase pull down, liquid chromatography-tandem mass spectrometry, and western blotting analyses demonstrated that this motif could bind with the gamma2-COP subcomplex of coat protein complex I (COPI), which is involved in the retrieval and transport of ER-resident proteins from the Golgi apparatus to the ER. Overall, we report a new hydrophobic peptide that possesses an arginine-based ER localization motif, which can help elucidate the mechanisms of ER sorting mediated by COPI. PMID- 27005821 TI - EM structure of a helicase-loader complex depicting a 6:2 binding sub stoichiometry from Geobacillus kaustophilus HTA426. AB - During DNA replication, bacterial helicase is recruited as a complex in association with loader proteins to unwind the parental duplex. Previous structural studies have reported saturated 6:6 helicase-loader complexes with different conformations. However, structural information on the sub stoichiometric conformations of these previously-documented helicase-loader complexes remains elusive. Here, with the aid of single particle electron microscopy (EM) image reconstruction, we present the Geobacillus kaustophilus HTA426 helicase-loader (DnaC-DnaI) complex with a 6:2 binding stoichiometry in the presence of ATPgammaS. In the 19 A resolution EM map, the undistorted and unopened helicase ring holds a robust loader density above the C-terminal RecA like domain. Meanwhile, the path of the central DNA binding channel appears to be obstructed by the reconstructed loader density, implying its potential role as a checkpoint conformation to prevent the loading of immature complex onto DNA. Our data also reveals that the bound nucleotides and the consequently induced conformational changes in the helicase hexamer are essential for active association with loader proteins. These observations provide fundamental insights into the formation of the helicase-loader complex in bacteria that regulates the DNA replication process. PMID- 27005822 TI - CAST your vote: is calpain inhibition the answer to ALS? AB - A publication in the Journal of Neurochemistry by Rao et al. (2016) suggests that the overexpression of the calpain inhibitor, calpastatin (CAST) rescues neuron loss and increases survival of the amyotrophic lateral sclerosis (ALS) mouse model, hSOD1G93A. The findings of Rao et al. (2016) provide an insight into the mechanisms that lead to neuronal loss in ALS and suggest a cell loss pathway common to several neurodegenerative disorders that may be therapeutically targeted. Here, we highlight the findings of Rao et al. (2016) and discuss some key considerations required prior to assessing the potential use of calpain inhibitors in the clinic. Read the highlighted article 'Calpastatin inhibits motor neuron death and increases survival in hSOD1(G93A) mice' on page 253. PMID- 27005824 TI - On-off Bodipy chemosensor for recognition of iron(III) ion based on the inner filter effect and its applications in cellular and bacterial imaging. AB - One strong fluorescent Bodipy-containing derivative was synthesized and characterized using 1 H NMR, electrospray ionization mass spectrometry and elemental analysis. Its electrochemical and photophysical properties were investigated. In addition, the Bodipy derivative could be used as an on-off fluorescent probe for the detection of Fe3+ ions based on the inner filter effect because the absorption band of the Fe3+ ion overlaps the excitation band of Bodipy very well upon irradiation with UV light. Furthermore, the Bodipy-based sensor has obvious advantages including simplicity, rapid response, high selectivity, sensitivity and a detection limit of 1.2 MUmol/L, and has been demonstrated in real water samples including tap water, mineral water and water from Lake Tai. Moreover, the fluorescent probe could also be used as a probe for the determination of Fe3+ in cellular and bacterial imaging. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27005823 TI - Abscisic acid and sucrose regulate tomato and strawberry fruit ripening through the abscisic acid-stress-ripening transcription factor. AB - Although great progress has been made towards understanding the role of abscisic acid (ABA) and sucrose in fruit ripening, the mechanisms underlying the ABA and sucrose signalling pathways remain elusive. In this study, transcription factor ABA-stress-ripening (ASR), which is involved in the transduction of ABA and sucrose signalling pathways, was isolated and analysed in the nonclimacteric fruit, strawberry and the climacteric fruit, tomato. We have identified four ASR isoforms in tomato and one in strawberry. All ASR sequences contained the ABA stress- and ripening-induced proteins and water-deficit stress-induced proteins (ABA/WDS) domain and all ASR transcripts showed increased expression during fruit development. The expression of the ASR gene was influenced not only by sucrose and ABA, but also by jasmonic acid (JA) and indole-3-acetic acid (IAA), and these four factors were correlated with each other during fruit development. ASR bound the hexose transporter (HT) promoter, which contained a sugar box that activated downstream gene expression. Overexpression of the ASR gene promoted fruit softening and ripening, whereas RNA interference delayed fruit ripening, as well as affected fruit physiological changes. Change in ASR gene expression influenced the expression of several ripening-related genes such as CHS, CHI, F3H, DFR, ANS, UFGT, PG, PL, EXP1/2, XET16, Cel1/2 and PME. Taken together, this study may provide new evidence on the important role of ASR in cross-signalling between ABA and sucrose to regulate tomato and strawberry fruit ripening. The findings of this study also provide new insights into the regulatory mechanism underlying fruit development. PMID- 27005827 TI - [Chronic hepatothorax due to right diaphragmatic rupture: an anesthetic challenge in a rare case]. AB - BACKGROUND: Diaphragmatic rupture is an uncommon condition, with 90% of ruptures occurring on the left side. However, its incidence on the right side is increasing along with the increase in traffic accidents. Liver herniation may become progressive causing severe atelectasis of the right lung, resulting in impaired respiratory status and hemodynamic changes. CASE REPORT: We report the case of a 40 years old female, ASA III, scheduled for hepatothorax repair that evolved from right diaphragmatic hernia after a car accident when she was 8 years old. Clinically, she had severe restrictive respiratory syndrome caused by the hepatothorax. The anesthetic evaluation was normal, except for the chest X-ray showing elevation of the dome of the right hemidiaphragm without tracheal deviation. Diagnosis was confirmed by CT scan. After liver replacement in the abdominal cavity, a transient increase in central venous pressure, stroke volume index and flow time corrected (35%), and a decrease in systemic vascular resistance were observed. After complete hemodynamic and hepatosplenic stabilization, as well as ventilation, the patient was transferred intubated, under controlled ventilation and monitored, to the liver transplant unit. CONCLUSIONS: Hepatothorax is a rare condition and its repair may represent an anesthetic challenge. After liver replacement in the abdominal cavity during corrective surgery under general anesthesia complications may occur, particularly associated with pulmonary re-expansion. Effective teamwork and careful planning of surgery, between the surgical and anesthetic teams, are the key to success. PMID- 27005826 TI - Severe Traumatic Brain Injury: A Case Report. AB - BACKGROUND: Traumatic brain injury remains a challenging and complicated disease process to care for, despite the advance of technology used to monitor and guide treatment. Currently, the mainstay of treatment is aimed at limiting secondary brain injury, with the help of multiple specialties in a critical care setting. Prognosis after TBI is often even more challenging than the treatment itself, although there are various exam and imaging findings that are associated with poor outcome. These findings are important because they can be used to guide families and loved ones when making decisions about goals of care. CASE REPORT: In this case report, we demonstrate the unanticipated recovery of a 28-year-old male patient who presented with a severe traumatic brain injury after being in a motorcycle accident without wearing a helmet. He presented with several exam and imaging findings that are statistically associated with increased mortality and morbidity. CONCLUSIONS: The care of severe traumatic brain injuries is challenging and dynamic. This case highlights the unexpected recovery of a patient and serves as a reminder that there is variability among patients. PMID- 27005825 TI - Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. AB - BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, the etiology of which involves a strong genetic component, but much of the underlying genetic determinants still remain unknown. Our aim was to identify novel genetic variants that predispose to JIA. METHODS: We performed a genome-wide association study (GWAS) and replication in a total of 1166 JIA cases and 9500 unrelated controls of European ancestry. Correlation of SNP genotype and gene expression was investigated. Then we conducted targeted resequencing of a candidate locus, among a subset of 480 cases and 480 controls. SUM test was performed to evaluate the association of the identified rare functional variants. RESULTS: The CXCR4 locus on 2q22.1 was found to be significantly associated with JIA, peaking at SNP rs953387. However, this result is subjected to subpopulation stratification within the subjects of European ancestry. After adjusting for principal components, nominal significant association remained (p < 10(-4)). Because of its interesting known function in immune regulation, we carried out further analyses to assess its relationship with JIA. Expression of CXCR4 was correlated with CXCR4 rs953387 genotypes in lymphoblastoid cell lines (p = 0.014) and T-cells (p = 0.0054). In addition, rare non-synonymous and stop-gain sequence variants in CXCR4, putatively damaging for CXCR4 function, were significantly enriched in JIA cases (p = 0.015). CONCLUSION: Our results suggest the association of CXCR4 variants with JIA, implicating that this gene may be involved in the pathogenesis of autoimmune disease. However, because this locus is subjected to population stratification within the subjects of European ancestry, additional replication is still necessary for this locus to be considered a true risk locus for JIA. This cell-surface chemokine receptor has already been targeted in other diseases and may serve as a tractable therapeutic target for a specific subset of pediatric arthritis patients with additional replication and functional validation of the locus. PMID- 27005828 TI - [Hyperglycemia assessment in the post-anesthesia care unit]. AB - BACKGROUND AND OBJECTIVES: Hyperglycemia in surgical patients may cause serious problems. Analyzing this complication in this scenario contributes to improve the management of these patients. The aim of this study was to evaluate the prevalence of hyperglycemia in the post-anesthetic care unit (PACU) in non diabetic patients undergoing elective surgery and analyze the possible risk factors associated with this complication. METHODS: We evaluated non-diabetic patients undergoing elective surgeries and admitted in the PACU. Data were collected from medical records through precoded questionnaire. Hyperglycemia was considered when blood glucose was>120mg.dL-1. Patients with hyperglycemia were compared to normoglycemic ones to assess factors associated with the problem. We excluded patients with endocrine-metabolic disorders, diabetes, children under 18 years, body mass index (BMI) below 18 or above 35, pregnancy, postpartum or breastfeeding, history of drug use, and emergency surgeries. RESULTS: We evaluated 837 patients. The mean age was 47.8+/-16.1 years. The prevalence of hyperglycemia in the postoperative period was 26.4%. In multivariate analysis, age (OR=1.031, 95% CI 1.017-1.045); BMI (OR=1.052, 95% CI 1.005-1.101); duration of surgery (OR=1.011, 95% CI 1.008-1.014), history of hypertension (OR=1.620, 95% CI 1.053-2.493), and intraoperative use of corticosteroids (OR=5.465, 95% CI 3.421-8.731) were independent risk factors for postoperative hyperglycemia. CONCLUSION: The prevalence of hyperglycemia was high in the PACU, and factors such as age, BMI, corticosteroids, blood pressure, and duration of surgery are strongly related to this complication. PMID- 27005829 TI - Pulsed-laser micropatterned quantum-dot array for white light source. AB - In this study, a novel photoluminescent quantum dots device with laser-processed microscale patterns has been demonstrated to be used as a white light emitting source. The pulsed laser ablation technique was employed to directly fabricate microscale square holes with nano-ripple structures onto the sapphire substrate of a flip-chip blue light-emitting diode, confining sprayed quantum dots into well-defined areas and eliminating the coffee ring effect. The electroluminescence characterizations showed that the white light emission from the developed photoluminescent quantum-dot light-emitting diode exhibits stable emission at different driving currents. With a flexibility of controlling the quantum dots proportions in the patterned square holes, our developed white-light emitting source not only can be employed in the display applications with color triangle enlarged by 47% compared with the NTSC standard, but also provide the great potential in future lighting industry with the correlated color temperature continuously changed in a wide range. PMID- 27005830 TI - Hybrid Repair of Aortic Arch Aneurysms with Endografting of the Ascending Aorta. AB - BACKGROUND: Different "hybrid" techniques that combine open debranching of the supra-aortic vessels with endografting of the aortic arch have emerged as alternatives to the open arch repair in high-risk patients. This study aims to review the early and mid-term results of single-stage hybrid arch repair with ascending aorta stent graft deployment for aortic arch aneurysms and dissections. METHODS: Between June 2006 and May 2015, five consecutive patients, with an age range of 54-78 years, with complex aortic arch diseases, were treated with a hybrid approach in which the endograft had a proximal landing zone in the ascending aorta. Indications included: acute and chronic type A aortic dissections and three arch aneurysms associated with distal aortic pathology. Length of postoperative clinical and imaging follow-up ranged from 10 to 121 months and was completed in all patients. RESULTS: Technical success of the endografting was achieved in all cases. There was one in-hospital mortality secondary to pulmonary embolism, one case of retrograde type A aortic dissection (RTAD) detected before discharge and one case of late type Ib endoleak that required an endografting procedure. No postoperative stroke or transient or permanent spinal cord ischemia occurred. CONCLUSION: Hybrid arch repair with endograft landing in zone 0 may decrease mortality and morbidity in high-risk patients. doi: 10.1111/jocs.12735 (J Card Surg 2016;31:341-347). PMID- 27005832 TI - Utilization of HPASubC for the Identification of Sinusoid-Specific Proteins in the Liver. AB - Mass spectrometry-based proteomes of human organs and tissues are powerful tools but fail to capture protein localization and expression at the cellular level. For example, the proteome signal in liver represents the combined protein expression across diverse cellular constituents that include hepatocytes, Kupffer cells, endothelial cells, and others. We utilized HPASubC and the Human Protein Atlas (HPA) to identify the sinusoidal component of protein liver expression to further subset and organize this homogeneous signal. We evaluated 51 109 liver images covering 13 197 proteins from the HPA and discovered 1054 proteins that were exclusive to sinusoidal cells. Sinusoidal staining patterns were identified in a Kupffer cell (n = 247), endothelial cell (n = 358), or lymphocyte (n = 86) specific pattern. Two-hundred and thirty-nine of these proteins were not present in the NextProt or Human Proteome Map liver data sets, potentially expanding our knowledge of the liver proteome. We additionally demonstrate unique endothelial cell expression patterns that distinguish between portal vein, hepatic artery, capillary sinusoids, and central vein regions. These findings significantly improve our understanding of the liver proteome with insight into the endothelial complexity across the hepatic vascular network. PMID- 27005831 TI - Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. AB - Intestinal immune homeostasis requires dynamic crosstalk between innate and adaptive immune cells. Dendritic cells (DCs) exist as multiple phenotypically and functionally distinct sub-populations within tissues, where they initiate immune responses and promote homeostasis. In the gut, there exists a minor DC subset defined as CD103(+)CD11b(-) that also expresses the chemokine receptor XCR1. In other tissues, XCR1(+) DCs cross-present antigen and contribute to immunity against viruses and cancer, however the roles of XCR1(+) DCs and XCR1 in the intestine are unknown. We showed that mice lacking XCR1(+) DCs are specifically deficient in intraepithelial and lamina propria (LP) T cell populations, with remaining T cells exhibiting an atypical phenotype and being prone to death, and are also more susceptible to chemically-induced colitis. Mice deficient in either XCR1 or its ligand, XCL1, similarly possess diminished intestinal T cell populations, and an accumulation of XCR1(+) DCs in the gut. Combined with transcriptome and surface marker expression analysis, these observations lead us to hypothesise that T cell-derived XCL1 facilitates intestinal XCR1(+) DC activation and migration, and that XCR1(+) DCs in turn provide support for T cell survival and function. Thus XCR1(+) DCs and the XCR1/XCL1 chemokine axis have previously-unappreciated roles in intestinal immune homeostasis. PMID- 27005834 TI - Diminished heart rate reactivity to acute psychological stress is associated with enhanced carotid intima-media thickness through adverse health behaviors. AB - Recent evidence demonstrates that individuals with low heart rate (HR) reactions to acute psychological stress are more likely to be obese or smokers. Smoking and obesity are established risk factors for increased carotid intima-media thickness (IMT). The aim of this study was to examine the potential pathways linking intima media thickness, smoking, body mass index (BMI), and HR stress reactivity. A total of 552 participants, 47.6% male, M (SD) age = 58.3 (0.94) years, were exposed to three psychological stress tasks (Stroop, mirror drawing, and speech) preceded by a resting baseline period; HR was recorded throughout. HR reactivity was calculated as the average response across the three tasks minus average baseline HR. Smoking status, BMI, and IMT were determined by trained personnel. Controlling for important covariates (e.g., socioeconomic status), structural equation modeling revealed that BMI and smoking mediated the negative relationship between HR reactivity and IMT. The hypothesized model demonstrated a good overall fit to the data, chi(2) (8) = 0.692, p = .403; CFI = 1.00; TLI = 1.00 SRMR = .01; RMSEA < .001 (90% CI < 0.01-0.11). HR reactivity was negatively related to BMI (beta = -.16) and smoking (beta = -.18), and these in turn were positively associated with IMT (BMI: beta = .10; smoking: beta = .17). Diminished HR stress reactivity appears to be a marker for enlarged IMT and appears to be exerting its impact through already established risks. Future research should examine this relationship longitudinally and aim to intervene early. PMID- 27005833 TI - Acetylation of C/EBPalpha inhibits its granulopoietic function. AB - CCAAT/enhancer-binding protein alpha (C/EBPalpha) is an essential transcription factor for myeloid lineage commitment. Here we demonstrate that acetylation of C/EBPalpha at lysine residues K298 and K302, mediated at least in part by general control non-derepressible 5 (GCN5), impairs C/EBPalpha DNA-binding ability and modulates C/EBPalpha transcriptional activity. Acetylated C/EBPalpha is enriched in human myeloid leukaemia cell lines and acute myeloid leukaemia (AML) samples, and downregulated upon granulocyte-colony stimulating factor (G-CSF)- mediated granulocytic differentiation of 32Dcl3 cells. C/EBPalpha mutants that mimic acetylation failed to induce granulocytic differentiation in C/EBPalpha-dependent assays, in both cell lines and in primary hematopoietic cells. Our data uncover GCN5 as a negative regulator of C/EBPalpha and demonstrate the importance of C/EBPalpha acetylation in myeloid differentiation. PMID- 27005835 TI - Determination of alkaloids in onion nectar by micellar electrokinetic chromatography. AB - Nectar is the most important floral reward offered by plants to insects. Minor components such as alkaloid compounds in nectar affect bee foraging, with great influence in seed production. CE is an advantageous tool for the analysis of unexplored samples such as onion nectar due to the limited amounts of samples. Considering the importance of these compounds, a simultaneous determination of nicotine, theophylline, theobromine, caffeine, harmaline, piperine in onion nectar by MEKC-UV is herein reported. The extraction of alkaloid compounds in nectar was performed by SPE using a homemade miniaturized column (C18 ). Effects of several important factors affecting extraction efficiency as well as electrophoretic performance were investigated to acquire optimum conditions. Under the proposed conditions, the analytes can be separated within 15 min in a 50 cm effective length capillary (75 MUm id) at a separation voltage of 20 kV in 20 mmol/L sodium tretraborate, 100 mmol/L SDS. The amount of sample requirement was reduced up to 2000 times, when compared to traditional methods, reaching limits of detection as low as 0.0153 ng/L. For the first time, this study demonstrates that there are marked qualitative and quantitative differences in nectar alkaloids between open pollinated and male sterile lines (MSLs) and also within MSLs. PMID- 27005836 TI - Human factors and ergonomics for primary care. AB - In the second paper of this series, we provide a brief overview of the scientific discipline of human factors and ergonomics (HFE). Traditionally the HFE focus in healthcare has been in acute hospital settings which are perceived to exhibit characteristics more similar to other high-risk industries already applying related principles and methods. This paper argues that primary care is an area which could benefit extensively from an HFE approach, specifically in improving the performance and well-being of people and organisations. To this end, we define the purpose of HFE, outline its three specialist sub-domains (physical, cognitive and organisational HFE) and provide examples of guiding HFE principles and practices. Additionally, we describe HFE issues of significance to primary care education, improvement and research and outline early plans for building capacity and capability in this setting. PMID- 27005837 TI - Reducing general practice trainees' antibiotic prescribing for respiratory tract infections: an evaluation of a combined face-to-face workshop and online educational intervention. AB - Over-prescription of antibiotics for non-pneumonia respiratory tract infections (RTIs) is a major concern in general practice. Australian general practice registrars (trainees) have inappropriately high rates of prescription of antibiotics for RTIs. The 'apprenticeship' educational model and the trainee trainer relationship are drivers of this inappropriate prescribing. We aimed to reduce registrars' non-pneumonia RTI antibiotic prescribing via an educational intervention (a 90-min face-to-face workshop supported by online modules), complemented by delivery of the same intervention, separately, to their trainers. We conducted a pre- and post-intervention comparison of the registrars' intention to prescribe antibiotics for common RTIs using McNemar's test. We similarly tested changes in supervisors' intended prescribing. Prescribing intentions were elicited by responses to six written clinical vignettes (upper respiratory tract infection, otitis media, sore throat and three acute bronchitis vignettes). We found that, for registrars, there were statistically significant reductions in antibiotic prescribing for the sore throat (24.0% absolute reduction), otitis media (17.5% absolute reduction) and two of the three acute bronchitis (12.0% and 18.0% absolute reduction) vignettes. There were significant reductions in supervisors' antibiotic prescribing intentions for the same four vignettes. We conclude that our intervention produced a significant change in registrars' intention to prescribe antibiotics for non-pneumonia RTIs. PMID- 27005838 TI - 'It gave me a new lease of life ... ': GPs' views and experiences of supervising foundation doctors in general practice. AB - BACKGROUND: General practice is a popular placement in the second year of Foundation training. Evaluations suggest this is a positive experience for most trainee doctors and benefits their perceptions of primary care, but the impact on primary care supervisors has not been considered. At a time when placements may need to increase, understanding the experience of the GP supervisors responsible for these placements is important. AIM: To explore the views, experiences and needs of GPs who supervise F2 doctors in their practices including their perceptions of the benefits to individuals and practices. DESIGN AND SETTING: A qualitative approach with GPs from across Severn Postgraduate Medical Education who supervise F2 doctors. METHOD: Semi-structured interviews with 15 GPs between December 2012 and April 2013. RESULTS: GP supervisors are enthusiastic about helping F2 doctors to appreciate the uniqueness of primary care. Workload and responsibility around supervision is considerable making a supportive team important. Working with young, enthusiastic doctors boosts morale in the team. The presence of freshly trained minds prompts GPs to consider their own learning needs. Being a supervisor can increase job satisfaction; the teaching role gives respite from the demanding nature of GP work. CONCLUSION: Supervisors are positive about working with F2s, who lift morale in the team and challenge GPs in their own practice and learning. This boosts job and personal satisfaction. Nonetheless, consideration should be given to managing teaching workload and team support for supervision. PMID- 27005840 TI - Developing communication skills with GP trainees: the REAM approach. PMID- 27005839 TI - Impact of revalidation on appraisal in primary care: an initial evaluation of the experience of Welsh GPs. AB - BACKGROUND: While appraisal is a well-established process and has been a contractual obligation for GPs in Wales since 2004, revalidation is a new requirement for all doctors practising in the UK. Appraisal is an essential component of revalidation. However as appraisal is developmental, and revalidation is summative, there is concern over the potential impact revalidation may have on the appraisal process itself. METHODS: This study, carried out among GPs in Wales, aimed to capture participants' perspectives of the initial impact of revalidation on appraisal. The study was commenced by conducting a basic literature review, building on existing research in this area. We employed a mixed method approach (an online survey and focus groups). The online survey was disseminated via Bristol Online Survey. Focus groups were carried out to examine the perspectives of both GP Appraisers and GPs on the study subject matter. RESULTS: The majority of respondents felt that revalidation had had a medium-sized effect on the appraisal process. Respondents were fairly evenly divided on the nature of that impact. Some reported collecting GMC specified information had increased time costs. Others found that collecting this information had sparked reflection and changes to their practice. GPs were fairly evenly divided on the precise extent to which the GMC data collection offered an accurate picture of their work and learning. The majority felt that it did, with 20-23% reporting a negative impact. CONCLUSION: The study participants reported that revalidation had impacted on appraisal, bringing increased time and costs alongside some increased individual reflection and Quality Improvement (QI) activity. The impact was felt more by appraisers than appraisees. Overall, of those GPs revalidated in 2013, 62% reported it was a positive experience. PMID- 27005841 TI - Undertake ethically sound medical education research. AB - There are key ethical principles that need to be considered before the start of any research study. The research should be designed, reviewed and conducted in ways that ensure the integrity and the quality of the work. Researchers and research participants need to be fully informed as to the purpose, methods and possible uses of the study. Participation needs to be voluntary with a right to withdraw at any stage clearly stated. Anonymity and confidentiality must be respected and maintained, within the usual caveats of potential for danger or harm. Ethical approval must be obtained from an appropriate professional body or group. This is an essential step which should not be overlooked as it affords objective scrutiny to each piece of research and also publication will not proceed without confirmation of its having being achieved. PMID- 27005842 TI - Overcoming challenges in primary care education: family physician education in Newfoundland and Labrador. PMID- 27005844 TI - Autophagy regulates the apoptosis of bone marrow-derived mesenchymal stem cells under hypoxic condition via AMP-activated protein kinase/mammalian target of rapamycin pathway. AB - Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been demonstrated as an ideal autologous stem cells source for cell-based therapy for myocardial infarction (MI). However, poor viability of donor stem cells after transplantation limits their therapeutic efficiency, whereas the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for maintaining homeostasis and normal function. Here, we investigated the potential role of autophagy on apoptosis in BM-MSCs induced by hypoxic injury. BM-MSCs, isolated from male C57BL/6 mice, were subjected to hypoxia and serum deprivation (H/SD) injury for 6, 12, and 24 h, respectively. The autophagy state was regulated by 3-methyladenine (3MA) and rapamycin administration. Furthermore, compound C was administrated to inhibit AMPK. The apoptosis induced by H/SD was determined by TUNEL assays. Meanwhile, autophagy was measured by GFP-LC3 plasmids transfection and transmission electron microscope. Moreover, protein expressions were evaluated by Western blot assay. In the present study, we found that hypoxic stress increased autophagy and apoptosis in BM-MSCs time dependently. Meanwhile, hypoxia increased the activity of AMPK/mTOR signal pathway. Moreover, increased apoptosis in BM-MSCs under hypoxia was abolished by 3-MA, whereas was aggravated by rapamycin. Furthermore, the increased autophagy and apoptosis in BM-MSCs induced by hypoxia were abolished by AMPK inhibitor compound C. These data provide evidence that hypoxia induced AMPK/mTOR signal pathway activation which regulated the apoptosis and autophagy in BM-MSCs. Furthermore, the apoptosis of BM-MSCs under hypoxic condition was regulated by autophagy via AMPK/mTOR pathway. PMID- 27005843 TI - Nuquantus: Machine learning software for the characterization and quantification of cell nuclei in complex immunofluorescent tissue images. AB - Determination of fundamental mechanisms of disease often hinges on histopathology visualization and quantitative image analysis. Currently, the analysis of multi channel fluorescence tissue images is primarily achieved by manual measurements of tissue cellular content and sub-cellular compartments. Since the current manual methodology for image analysis is a tedious and subjective approach, there is clearly a need for an automated analytical technique to process large-scale image datasets. Here, we introduce Nuquantus (Nuclei quantification utility software) - a novel machine learning-based analytical method, which identifies, quantifies and classifies nuclei based on cells of interest in composite fluorescent tissue images, in which cell borders are not visible. Nuquantus is an adaptive framework that learns the morphological attributes of intact tissue in the presence of anatomical variability and pathological processes. Nuquantus allowed us to robustly perform quantitative image analysis on remodeling cardiac tissue after myocardial infarction. Nuquantus reliably classifies cardiomyocyte versus non-cardiomyocyte nuclei and detects cell proliferation, as well as cell death in different cell classes. Broadly, Nuquantus provides innovative computerized methodology to analyze complex tissue images that significantly facilitates image analysis and minimizes human bias. PMID- 27005845 TI - Soyasaponin Bb inhibits the recruitment of toll-like receptor 4 (TLR4) into lipid rafts and its signaling pathway by suppressing the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent generation of reactive oxygen species. AB - SCOPE: We and others recently showed that soyasaponin Bb (SSBb ) inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages. Since the recruitment of toll-like receptor 4 (TLR4) into lipid rafts is vital for LPS initiated signaling, we investigated whether this process would be modulated by SSBb . METHODS AND RESULTS: By using sucrose gradient ultracentrifuge, we found that pretreatment of macrophages with SSBb inhibited LPS-induced recruitments of TLR4, myeloid differentiation primary response protein 88 (MyD88) and Toll/IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF) into fractions enriched with lipid rafts marker flotillin-1. We also found SSBb decreased co localization of TLR4 and lipid rafts by utilizing confocal immunofluorescence microscopy. Additionally, we observed that SSBb suppressed LPS-induced formation of TLR4/MyD88 and TLR4/TRIF complexes, production of pro-inflammatory molecules, and activation of nuclear factor kappa B (NF-kappaB). Furthermore, we found that these inhibitory effects of SSBb were associated with reduced reactive oxygen species (ROS) because pretreating cells with N-acetyl-L-cysteine and NADPH oxidase inhibitor diphenyleneiodonium (DPI) inhibited LPS-induced TLR4 recruitment into lipid rafts and NF-kappaB activation. SSBb also inhibited NADPH oxidase activation by blocking interaction between gp91(phox) and p47(phox) similarly as DPI. CONCLUSION: SSBb can inhibit TLR4 recruitment into lipid rafts and its signaling by suppressing the NADPH oxidase-dependent ROS generation. PMID- 27005846 TI - The echoes of intoxication. PMID- 27005847 TI - Versatile, mild, and selective reduction of various carbonyl groups using an electron-deficient boron catalyst. AB - A mild and selective new method was discovered to reduce acetanilides and other carbonyl compounds. Unlike sodium borohydride, which is selective in reducing aldehydes and ketones, this new protocol is uniquely selective in reducing acetanilides and nitriles over other carbonyl containing functional groups. Additionally, beta-ketoamides were shown to be reduced at the ketone preferentially over the amide. PMID- 27005849 TI - Analytical challenges and solutions in doping control: a perspective from the Swedish Doping Control Laboratory. PMID- 27005848 TI - Development and validation of HILIC-ESI/MS/MS methods for simultaneous quantitation of several antipsychotics in human plasma and blood. AB - BACKGROUND: Knowledge of antipsychotic drug levels at point of care (POC) may significantly aid therapeutic decision-making. To support the development of future POC devices and to validate the use of fingerstick capillary blood sampling, two robust hydrophilic interaction LC-ESI/MS/MS methods were developed and validated. Two PK studies were completed evaluating the correlation between fingerstick blood and plasma concentrations with corresponding venous blood and plasma concentrations for several commonly prescribed atypical antipsychotics and selected metabolites. Sensitive and reliable LC-MS/MS bioanalytical assays were developed to support these studies. RESULTS: Three methods, requiring only 25-MUl matrix volumes, were developed using supported liquid extraction with hydrophilic interaction LC-MS/MS detection and validated according to regulatory guidance. CONCLUSION: Robust and efficient LC-MS/MS assays were established and were effective in providing antipsychotic drug matrix comparator results in the intended clinical studies. PMID- 27005850 TI - Sol-gel approach for extracting highly versatile aspirin and its metabolites using MISPE followed by GC-MS/MS analysis. AB - AIM: Aspirin is known to be a salicylate drug widely used as an analgesic, antipyretic and anti-inflammatory drug. METHODOLOGY: Sol-gel based nanosized molecularly imprinted polymer (nMIP) has been synthesized for extraction of aspirin and its metabolites in urine followed by GC-MS/MS analysis. RESULTS: Binding affinity of nMIP and nonimprinted polymer was found to be in the range of 70-95% and 29-45%, respectively. LOD and LOQ of aspirin and its metabolites were found to be in the range of 0.63-2.4 ng/ml and 2.07-7.68 ng/ml, respectively. CONCLUSION: The developed method was found to be applicable for routine analysis of aspirin and its metabolites in biological samples. PMID- 27005851 TI - Electrically stimulated liquid-based extraction techniques in bioanalysis. AB - Sample preparation is a vital and inseparable part of an analytical procedure. This issue has motivated the analytical research community around the world to develop new, fast and cost-effective extraction methods which can eliminate interfering substances, provide high preconcentration factors and increase the determination sensitivity. Electrical field induced extraction technique is a topic that has received major attention in recent years. This fact can be attributed to the considerable advantages provided by imposition of an electrical driving force especially control of different properties of an extraction system such as selectivity, cleanup, rate and efficiency. In this review, focus is centered on the electrical field induced liquid phase extraction techniques and their potential for bioanalysis. PMID- 27005852 TI - The use of stable isotope-labeled drug as microtracers with conventional LC-MS/MS to support human absolute bioavailability studies: are we there yet? PMID- 27005853 TI - Techniques and technologies for the bioanalysis of Sativex(r), metabolites and related compounds. AB - Sativex((r)) is an oromucosal spray indicated for the treatment of moderate-to severe spasticity in multiple sclerosis and is also an effective analgesic for advanced cancer patients. Sativex contains Delta(9)-tetrahydrocannabinol (THC) and cannabidiol in an approximately 1:1 ratio. The increasing prevalence of medicinal cannabis products highlights the importance of reliable bioanalysis and re-evaluation of the interpretation of positive test results for THC, as legal implications may arise in workplace, roadside and sports drug testing situations. This article summarizes published research on the bioanalysis of THC and cannabidiol, with particular focus on Sativex. Common screening and confirmatory testing of blood, urine, oral fluid and hair samples are outlined. Correlations between matrices and current analytical pitfalls are also addressed. PMID- 27005854 TI - Techniques for quantitative LC-MS/MS analysis of protein therapeutics: advances in enzyme digestion and immunocapture. AB - LC-MS/MS has been investigated to quantify protein therapeutics in biological matrices. The protein therapeutics is digested by an enzyme to generate surrogate peptide(s) before LC-MS/MS analysis. One challenge is isolating protein therapeutics in the presence of large number of endogenous proteins in biological matrices. Immunocapture, in which a capture agent is used to preferentially bind the protein therapeutics over other proteins, is gaining traction. The protein therapeutics is eluted for digestion and LC-MS/MS analysis. One area of tremendous potential for immunocapture-LC-MS/MS is to obtain quantitative data where ligand-binding assay alone is not sufficient, for example, quantitation of antidrug antibody complexes. Herein, we present an overview of recent advance in enzyme digestion and immunocapture applicable to protein quantitation. PMID- 27005856 TI - Comparison of blood microsampling with DBS and conventional blood collection techniques used in a midazolam biostudy. AB - BACKGROUND: Quantitative DBS LC-MS/MS assay for midazolam was used to compare two sample collection techniques (venipuncture and finger prick) and the midazolam concentrations measured in plasma samples, DBS and dried plasma spots. METHODOLOGY: Midazolam was extracted from DBS cards and compared with whole blood collected from usual venipuncture. Dried plasma spots were also compared with plasma. The blood volume used as well as the temperature impact during the blood and plasma deposits was evaluated. Midazolam was administrated to six healthy subjects during a clinical trial to obtained blood and plasma samples for the statistical comparison. CONCLUSION: The method for midazolam using DBS was validated and showed an excellent performance. Excellent correlations were observed when the same collection procedures were used. PMID- 27005855 TI - Large-scale implementation of sequential protein and peptide immunoaffinity enrichment LC/nanoLC-MS/MS for human beta-nerve growth factor. AB - BACKGROUND: A previously described immunoaffinity (IA)-LC-MS/MS assay for human beta-nerve growth factor (beta-NGF) was implemented to support large-scale sample testing for multiple clinical trials. Methodology & results: The procedure was modified to increase throughput by simultaneous preparation of two 96-well plates and LC duty-cycle reduction. Robustness of the LC method and nano-ESI was ensured during large-scale assay execution by closely monitoring and, if needed, replacing system components prior to failure. Following validation, the assay was used to analyze approximately 19,000 samples from multiple clinical studies over several years. CONCLUSION: Routine implementation of the beta-NGF IA-LC-MS/MS assay supported drug development programs. This optimized assay format now serves as a template for other clinical protein biomarker assays. PMID- 27005857 TI - Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn's disease. AB - BACKGROUND: As surgical resection is not curative in Crohn's disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. AIMS: To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohn's disease. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohn's disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. RESULTS: Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In multivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% [1.6-48.6], p=0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% [1.4-11.2], p=0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. CONCLUSION: Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohn's disease. PMID- 27005858 TI - Limits of Evidence Based Medicine for rare diseases: The case of Budd-Chiari syndrome. PMID- 27005859 TI - Correlation of anemia status with worsening bowel damage as measured by Lemann Index in patients with Crohn's disease. AB - BACKGROUND: There is evidence that anemia in Crohn's disease (CD) is a predictor of disease severity. AIM: To evaluate if patterns of anemia over time showed correlation with aggressive disease trajectory, as characterized by change in Lemann Index (LI), which is a metric that quantifies bowel damage. METHODS: CD patients with 5 year (y) follow-up from a prospective registry were included. LI was calculated from the first (LI1) and last (LI2) clinical encounters. The change in score (LI2-LI1) or the Delta LI (DLI) was recorded. Patterns of anemia, healthcare utilization and disease activity scores were analyzed. RESULTS: A total of 389 CD patients with 5y follow-up formed the study population [median age 40y (IQR: 31-53); 57.3% female; median disease duration 12y (IQR: 6-20.5), overall surgical exposure 69%]. Patients with anemia had significantly higher LI1, LI2, DLI and also significantly higher healthcare utilization and indices of disease activity, than patients without anemia (p<0.001). CD patients with anemia for any duration during the study had OR of 2.15 (95% CI 1.29-3.57, p=0.003) for worsening bowel damage over the 5y. CONCLUSION: Based on a longitudinal analysis of CD patients, anemia status over time shows significant correlation with increasing Lemann index and aggressive disease trajectory. PMID- 27005860 TI - Comorbidities in functional gastrointestinal diseases: Do we need a lone ranger or a dream team? PMID- 27005861 TI - Chemical synthesis and characterization of elastin-like polypeptides (ELPs) with variable guest residues. AB - The properties of elastin-like polypeptides (ELPs), specifically the fact that they are soluble in aqueous buffers below and aggregate reversibly above a well defined transition temperature, are extensively used for protein purification, enzyme recycling, and more recently, for in vivo applications such as drug delivery and tissue engineering. ELPs are artificial but biocompatible polypeptides composed of pentameric repeats (Val-Pro-Gly-Xaa-Gly) containing different guest residues Xaa, derived from mammalian elastin. The temperature dependent aggregation and desaggregation of ELPs is controlled by composition of the pentameric repeats as well as the number of repetitive units within the ELP. External parameters such as ELP concentration, pH, and most importantly, salt effects heavily influence the transition temperature. Here, we explore the chemical synthesis of a series of 51mer peptides consisting of 10 pentameric ELP repeats with hydrophobic as well as charged guest residues such as isoleucine, leucine, alanine, lysine, and/or glutamate all prepared by Boc-based solid phase peptide synthesis. These guest residues expand the available toolbox of synthetic ELPs and provide ELPs that can be chemically modified and tuned to specific environments. An N-terminal cysteine is added allowing disulfide-based crosslinking of ELPs and to link synthetic ELPs to a recombinantly produced protein using native chemical ligation. Transition temperatures of all synthetic ELPs and the fusion construct were determined by measuring turbidity in solution and spanned a large temperature range between 25 and 70 degrees C, providing synthetically accessible ELPs with transition temperatures suitable for in vitro and in vivo applications. Cycling between their soluble and aggregate state has been observed at least 6 times without significant loss of material for all synthetic ELPs. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27005862 TI - Hypoxia attenuates anti-Aspergillus fumigatus immune responses initiated by human dendritic cells. AB - Aspergillus fumigatus is an opportunistic mould that causes invasive pulmonary aspergillosis (IPA), a life-threatening infection in immunocompromised patients. During the course of IPA, localised areas of tissue hypoxia occur. Bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. However, the influence of hypoxia on anti-fungal immunity has been largely unknown. We evaluated the impact of hypoxia on the human anti-A. fumigatus immune response. Human monocyte-derived dendritic cells (DCs) were stimulated in vitro with germ tubes of A. fumigatus under normoxia or hypoxia (1% O2 ), followed by analysis of DC viability, maturation and cytokine release. While DC viability was unaffected, hypoxia attenuated cytokine release from DCs and maturation of DCs upon stimulation with A. fumigatus. These data suggest that hypoxia at the site of A. fumigatus infection inhibits full activation and function of human DCs. Thereby, this study identified hypoxia as a crucial immune modulating factor in the human anti-fungal immune response that might influence the course and outcome of IPA in immunocompromised patients. PMID- 27005863 TI - Synthesis of ligand-free CZTS nanoparticles via a facile hot injection route. AB - Single-phase, ligand-free Cu2ZnSnS4 (CZTS) nanoparticles that can be dispersed in polar solvents are desirable for thin film solar cell fabrication, since water can be used as the solvent for the nanoparticle ink. In this work, ligand-free nanoparticles were synthesized using a simple hot injection method and the precursor concentration in the reaction medium was tuned to control the final product. The as-synthesized nanoparticles were characterized using various techniques, and were found to have a near-stoichiometric composition and a phase pure kesterite crystal structure. No secondary phases were detected with Raman spectroscopy or scanning transmission electron microscopy energy dispersive x-ray spectroscopy. Furthermore, high resolution transmission electron microscopy showed large-sized nanoparticles with an average diameter of 23 nm +/- 11 nm. This approach avoids all organic materials and toxic solvents that otherwise could hinder grain growth and limit the deposition techniques. In addition the synthesis route presented here results in nanoparticles of a large size compared to other ligand-free CZTS nanoparticles, due to the high boiling point of the solvents selected. Large particle size in CZTS nanoparticle solar cells may lead to a promising device performance. The results obtained demonstrate the suitability of the synthesized nanoparticles for application in low cost thin film solar cells. PMID- 27005864 TI - Highly Stable Double-Stranded DNA Containing Sequential Silver(I)-Mediated 7 Deazaadenine/Thymine Watson-Crick Base Pairs. AB - The oligonucleotide d(TX)9 , which consists of an octadecamer sequence with alternating non-canonical 7-deazaadenine (X) and canonical thymine (T) as the nucleobases, was synthesized and shown to hybridize into double-stranded DNA through the formation of hydrogen-bonded Watson-Crick base pairs. dsDNA with metal-mediated base pairs was then obtained by selectively replacing W-C hydrogen bonds by coordination bonds to central silver(I) ions. The oligonucleotide I adopts a duplex structure in the absence of Ag(+) ions, and its stability is significantly enhanced in the presence of Ag(+) ions while its double-helix structure is retained. Temperature-dependent UV spectroscopy, circular dichroism spectroscopy, and ESI mass spectrometry were used to confirm the selective formation of the silver(I)-mediated base pairs. This strategy could become useful for preparing stable metallo-DNA-based nanostructures. PMID- 27005866 TI - Preparation of a K(+) -imprinted polymer for the selective recognition of K(+) in food samples. AB - An analytical method is reported for the preparation of K(+) -imprinted nanoparticles using cryptand 222 as the complexing agent, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the crosslinker and 2,2' azobisisobutyronitrile as the radical initiator. The prepared particles have a diameter of 200-250 nm. The maximum adsorption capacity of potassium ion imprinted polymer particles was 120 MUmol/g. The optimum pH for quantitative extraction was 9.0. The nature of the eluent, eluent concentration, adsorption and desorption times, weight of the polymer material, aqueous phase, and desorption volumes were also studied. The relative selectivity coefficients of K(+) /Li(+) , K(+) /Na(+) , K(+) /Rb(+) and K(+) /Cs(+) were 48.10, 4.80, 29.70, and 43.4, respectively. The relative standard deviation and limit of detection of the method were obtained 1.61% and 4.62 ng/L, respectively. Finally, the method was applied for the determination of potassium ions from different samples using flame photometry. PMID- 27005865 TI - TEX101, a glycoprotein essential for sperm fertility, is required for stable expression of Ly6k on testicular germ cells. AB - TEX101, a germ cell-specific glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein, is associated with Ly6k during spermatogenesis in testis. Although both Tex101(-/-) and Ly6k(-/-) mice can produce morphologically intact spermatozoa, both knockout mice show an infertile phenotype due to a disorder of spermatozoa to migrate into the oviduct. Since Ly6k specifically interacts with TEX101, complex formation of TEX101/Ly6k appears to be potentially important for functional sperm production. This study evaluated the fate of Ly6k in the presence or absence of TEX101 to explore the molecular interaction of both GPI anchored proteins in seminiferous tubules. The present study showed that: 1) Although Ly6k mRNA was detected, the protein was present at very low levels in mature testes of Tex101(-/-) mice, 2) Ly6k mRNA level was within the normal range in Tex101(-/-) mice, 3) Ly6k mRNA was translated into a polypeptide in the testes of Tex101(+/+) and Tex101(-/-) mice, and 4) TEX101, as well as Ly6k, are co factors that affect to molecular expression. These results indicate that both TEX101 and Ly6k contribute to the post-translational counterpart protein expression at the cell membrane. This mechanism may be important in maintaining the production of fertile spermatozoa during spermatogenesis. PMID- 27005867 TI - Primary HPV testing: a proposal for co-testing in initial rounds of screening to optimise sensitivity of cervical cancer screening. AB - As explained by Kitchener in a previous issue of Cytopathology (2015;26:4-6), primary human papillomavirus (HPV) testing is likely to be introduced in the UK for all women aged 25-64 years following pilot site studies already in place. This will be necessary when the prevalence of cervical cancer and its precursors declines when vaccination takes effect but there is a risk in abandoning cytology as a primary test: a risk that would be most apparent in the present unvaccinated population in which the prevalence of cervical cancer and its precursors is exceptionally high. HPV testing is more sensitive than cytology but has a significant false-negative rate that could be detrimental to a successful screening programme if introduced without cytology backup. Accurate cytology would be needed for triage and could be compromised if HPV-negative tests were excluded from examination. This article proposes a compromise: cytology and HPV co-testing for the first two screening tests to optimise the sensitivity of the test as a whole. Registrations of invasive and in situ carcinoma of the uterine cervix in England indicate that the prevalence of the disease is highest in young women in the early rounds of screening. Calculations of the likely impact on the workload of this proposal have been based on a service evaluation of 295 cytology tests received at St Thomas' Hospital, which suggests that the volume of cytology tests would be reduced by approximately 60% compared with 80% for primary HPV testing alone. This proposal should be debated openly before irrevocable changes are made to a skilled workforce. PMID- 27005869 TI - The proposed change to primary HPV screening in New Zealand: reasons for caution. PMID- 27005868 TI - Public reporting of health care performance data: what we know and what we should do. PMID- 27005870 TI - Current management of acute diverticulitis: a survey of Australasian surgeons. AB - AIMS: To evaluate the current practice and degree of consensus amongst Australasian surgeons regarding non-surgical management of acute diverticulitis (AD) and to determine whether newer approaches to management are being translated into practice. METHODS: An online survey was distributed to all Australasian colorectal surgeons and all general surgeons in the Auckland region. Responses were collected over two months and analysed to identify points of consensus and areas of significant difference in opinion between these groups. RESULTS: Responses were received from a total of 99 of 200 (49.5%) colorectal surgeons, and 19 of 36 (52.7%) general surgeons. The Hinchey Classification was the most commonly used measure of disease severity, used by 67 (95.7%) colorectal surgeons and 12 (92.3%) general surgeons. There was lack of consensus around important aspects of AD management, including antibiotic therapy, and use and modality of follow-up imaging. Selective antibiotic therapy and use of anti-inflammatory medication as adjuncts to treatment were practised by a minority of those surveyed. CONCLUSIONS: Newer approaches to management were being utilised by some respondents. The lack of consensus regarding management of AD may be a consequence of a paucity of high-level evidence to support specific management approaches, particularly in patients with uncomplicated AD. PMID- 27005871 TI - Overnight transfusions in New Zealand hospitals: potential risk to patients. AB - AIMS: This audit aimed to assess how frequently overnight transfusions were taking place and compare it to the previous 2004 audit. METHOD: All red cell units transfused between 20:00 and 08:00 hours in low acuity areas over 4 weeks in 2010 in 8 of New Zealand's largest public hospitals were identified prospectively, followed by review of clinical notes and laboratory results by the hospital Transfusion Nurse Specialist (TNS). RESULTS: 535 red cell units were transfused overnight, or 9% of the total units administered over the study period. Indications for transfusion were symptomatic anaemia, active bleeding or haemolysis (66%), but 16% of patients were asymptomatic. Of the non-urgent overnight transfusions (OTs), 42% were assessed as non-essential during the night. 49% of post-transfusion haemoglobin (Hb) levels were >100 g/L indicating a liberal transfusion practice. Although frequently cited as a reason for OT, only 16% of patients were discharged the following day. The median interval from pre transfusion haemoglobin testing and starting the OT was approximately 9 hours, far exceeding the time needed to obtain routine full blood results. Adherence to recommended best transfusion practice was poor at night, with 12% of transfusions exceeding the 4 hour recommendation. End of transfusion observations fell to less than 80%, with the lowest compliance rate (69%) occurring at 06:00 hours. In addition to the 4 adverse reactions reported to the Haemovigilance programme, another 9 unreported reactions were identified by the auditors from the clinical notes. CONCLUSIONS: This audit has shown an improvement from 22% to 9% in the rate of OT compared to the 2004 audit. Nevertheless, 42% of transfusions were not considered appropriate based on current guidelines, and there is therefore room for improvement. A mean delay of 9 hours from haemoglobin sampling to transfusion suggests that reasons for this delay could be explored to help optimise transfusion start time. Some aspects of OT were worse than previously, with 12% of the OT exceeding 4 hours duration, double the rate of the previous audit. Results showing poor documentation and a high rate of unreported transfusion reactions (69% of reactions) suggest if an adverse transfusion reaction occurs overnight, there is a significant risk that it is less likely to be recognised, treated and/or reported. PMID- 27005872 TI - Management of gestational trophoblastic disease: a survey of New Zealand O&G practice. AB - AIM: The aim of the study was to obtain information on pathways for diagnosis and management of molar pregnancy/gestational trophoblastic disease (GTD) across New Zealand, the protocols used, and, in addition, to consider the view of O&G Specialists on a national GTD reference centre. METHOD: An electronic survey approved by the RANZCOG Continues Professional Development Committee was distributed amongst registered O&G Specialists currently working in New Zealand. Data were analysed using Microsoft Excel 2011. Frequency distributions were used to determine the percentage of participants responding to the listed alternatives for each question. RESULTS: There were 234 potential responders, but only 68 complete questionnaires were received and available for analysis. The diagnosis of GTD requires histopathological analysis of pregnancy tissue, however only 79.7% of participants request this test routinely. Sixty-five percent of Fellows thought that a number of molar pregnancies can be missed with increasing proportion of medically-managed miscarriages, reliance on ultrasound and appearance of the tissue being contributing factors. Sixty-six percent of specialists were directly involved in the management of patients with GTD to various degrees. Follow-up responsibilities were divided between designated O&G specialists (52.3%), specialised gynaecology clinics (29.2%), acute assessment units (13.8%), nurse specialists (12%), O&G registrars (10.8%), GPs (6.2%), and others (6.2%). NZGCG guidelines were used by the majority of responders (54.8%), followed by local (29%) and RCOG (27.4%) guidelines. Seventy-two percent of specialists felt that some form of centralisation in the management of GTD is needed. CONCLUSION: In spite of the low response rate, our research demonstrates existing practice heterogeneity at every level of care. It also confirms that there is a desire for some form of centralisation in diagnosis and management of GTD, and a definite need for data collection in the form of a national register. PMID- 27005873 TI - Accuracy of frozen sections for breast cancer sentinel lymph node biopsies within a peripheral New Zealand hospital. AB - AIM: Intra-operative frozen section is a commonly-used technique for evaluating sentinel lymph node biopsies in breast cancer to determine the need for an axillary node dissection (AND). Frozen section does have drawbacks, including cost and uncertainty around operating time. In addition, recent studies have questioned the benefit of AND in certain cases. The aim of this study was therefore to evaluate the accuracy of frozen section at our institution. METHODS: All patients who had a sentinel node biopsy for breast cancer in the Hawke's Bay District Health Board region over a 1-year period were included in the study. Results of intra-operative frozen section were compared to routine paraffin histological analysis. RESULTS: Eighty patients were eligible. Eighteen had a positive frozen section. There were two false negatives. The sensitivity of frozen section for metastases was 90%, specificity was 100%, and the false negative rate was 2.5%. CONCLUSIONS: The accuracy of frozen section section for sentinel lymph node biopsies in breast cancer at Hawke's Bay District Health Board is acceptable by international standards. However, as further evidence against axillary node dissections in those with sentinel node positive disease mounts, their use in the future may be limited. PMID- 27005874 TI - An exploratory study of the health harms and utilisation of health services of frequent legal high users under the interim regulated legal high market in central Auckland. AB - AIMS: To explore health problems and the accessing of health services by frequent legal high users under an interim regulated legal market in central Auckland. METHOD: Frequent legal high users (monthly+) were recruited from outside eight randomly-selected, licensed, legal high stores in central Auckland from 23 April 7 May, 2014. Eligible participants were emailed a unique invitation to complete an on-line survey; 105 completed the survey. RESULTS: Twenty-seven percent had suffered mental illness during their lifetimes. Eighty percent used synthetic cannabinoids (SC), and 20% 'party pills'. Forty-seven percent of SC users used daily or more often. Other drugs used included alcohol (80%), cannabis (59%), 'ecstasy' (18%) and methamphetamine (15%). Fifty-eight percent of SC users were classified as SC dependent. The most common problems reported from SC use were: insomnia (29%); 'vomiting/nausea' (25%); 'short temper/agitation' (21%); 'anxiety' (21%); 'strange thoughts' (16%); and 'heart palpitations' (14%). The health services most commonly accessed by SC users were: a 'doctor/GP' (9%); 'counsellor' (9%); 'DrugHelp/MethHelp' websites (7%); 'Alcohol & Drug Helpline' (4%); 'ambulance' (3%); 'A&E' (3%); and hospitalisation (3%). CONCLUSIONS: Frequent use of interim licensed SC products was associated with health problems, including dependency. Further research is required to determine the health risks of these products. PMID- 27005875 TI - Social and spatial inequalities in Rotaviral enteritis: a case for universally funded vaccination in New Zealand. AB - AIMS: Rotaviruses have long been recognised as the most common cause of diarrhoea related childhood morbidity and mortality worldwide. The benefits of national rotavirus vaccination programmes have been proven, with estimates of the reduction in hospital stays ranging from 70% to 90%. Previous work has found spatial variation in rotaviral rates between areas in Australia and Germany. This study sought to identify spatial and spatio-temporal variation in clustering of high and low neighbourhood rates of paediatric hospital admissions for RV disease in Auckland, New Zealand for the period 2006-2011. METHODS: Annual clusters of rotavirus hospitalisations were identified using a Local Moran's I Index from ArcGIS. Spatio-temporal variation during the study period used a retrospective spatial variation in temporal trends scan statistic in SatScan. RESULTS: Annual clusters of high and low rotavirus rates were identified for each year of the study and the spatio-temporal scan statistic confirmed that spatial clustering of rotavirus rates had shifted significantly during the study period. CONCLUSIONS: This research suggests that targeted rotaviral intervention is inappropriate and supports the introduction of a fully funded rotavirus vaccine in New Zealand in 2014. PMID- 27005877 TI - Valuing embryos as both commodities and singularities. AB - An argument put forward against gamete and embryo donation, sale and research, is that to do so would treat the gametes or embryos as objects with no intrinsic value as human. Instead, gametes and embryos created and used for donation, sale or research, can be considered more like a commodity created and traded for economic exchange--something that is valuable only for the amount of money or other goods and services that others are willing to exchange. While Kant asserts that humans have dignity rather than object worth, the provision of human gametes and embryos are progressively becoming utilities for resolving childlessness and for certain research investigations. In this paper we discuss the commodity market and the relationship to human reproduction material. PMID- 27005876 TI - Stroke care delivery at North Shore Hospital, Waitemata District Health Board 2014. PMID- 27005878 TI - Decision-making in an era of cancer prevention via aspirin: New Zealand needs updated guidelines and risk calculators. AB - Based on new systematic reviews of the evidence, the US Preventive Services Task Force has drafted updated guidelines on the use of low-dose aspirin for the primary prevention of both cardiovascular disease (CVD) and cancer. The Task Force generally recommends consideration of aspirin in adults aged 50-69 years with 10-year CVD risk of at least 10%, in who absolute health gain (reduction of CVD and cancer) is estimated to exceed absolute health loss (increase in bleeds). With the ongoing decline in CVD, current risk calculators for New Zealand are probably outdated, so it is difficult to be precise about what proportion of the population is in this risk category (roughly equivalent to 5-year CVD risk >=5%). Nevertheless, we suspect that most smokers aged 50-69 years, and some non smokers, would probably meet the new threshold for taking low-dose aspirin. The country therefore needs updated guidelines and risk calculators that are ideally informed by estimates of absolute net health gain (in quality-adjusted life-years (QALYs) per person) and cost-effectiveness. Other improvements to risk calculators include: epidemiological rigour (eg, by addressing competing mortality); providing enhanced graphical display of risk to enhance risk communication; and possibly capturing the issues of medication disutility and comparison with lifestyle changes. PMID- 27005879 TI - Perforated sigmoid colon carcinoma within a left inguinal hernia with associated necrotising infection. PMID- 27005880 TI - Time to establish a New Zealand/ Aotearoa Twin Registry? PMID- 27005881 TI - Colon cancer screening: the devil is in the details. PMID- 27005882 TI - Familial discrepancy of clinical outcomes associated with fibrinogen Dorfen: A case of huge genital hematoma after episiotomy. AB - This study demonstrates a case of a huge genital hematoma after delivery, associated with fibrinogen Dorfen. Fibrinogen Dorfen is the mutation of a fibrinogen-coded exon gene, which has a single heterozygous GCC -> GTC transition at codon 289 of the gamma gene, predicting an Ala -> Val substitution. Because Ala289 plays a crucial role in maintaining the structure of the polymerization site of hole 'a' via a hydrogen bond, it is speculated that the gamma 289Ala -> Val substitution can change not only the fibrinogen structure, but also the function of polymerization. In our case, although the patient's gene mutation was the same as that of her mother, there was a discrepancy in the clinical outcomes. Although the precise mechanism regarding this discrepancy remains unknown, it may cause different perinatal outcomes in terms of vaginal delivery, such as the severe bleeding in this patient and the absence of clinical symptoms in her mother. This is the first report suggesting the heterogeneity of fibrinogen functions of fibrinogen Dorfen, which may be critical to the clinical outcome. PMID- 27005883 TI - Dehydrogenation of methanol to formaldehyde catalyzed by pristine and defective ceria surfaces. AB - We have explored the dehydrogenation of methoxy on pristine and defective (111), (100), and (110) ceria surfaces with density functional methods. Methanol conversion is used as a probe reaction to understand structure sensitivity of the oxide catalysis. Differences in reaction selectivity have been observed experimentally as a function of crystallographically exposed faces and degree of reduction. We find that the barrier for carbon-hydrogen cleavage in methoxy is similar for the pristine and defective (111), (100), and (110) surfaces. However, there are large differences in the stability of the surface intermediates on the different surfaces. The variations in experimentally observed product selectivities are a consequence of the interplay between barrier controlled bond cleavage and desorption processes. Subtle differences in activation energies for carbon-hydrogen cleavage on the different crystallographic faces of ceria could not be correlated with structural or electronic descriptors. PMID- 27005884 TI - Calculating regional tissue volume for hyperthermic isolated limb perfusion: Four methods compared. AB - INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) can be performed as an alternative to amputation for soft tissue sarcomas and melanomas of the extremities. Melphalan and tumor necrosis factor-alpha are used at a dosage that depends on the volume of the limb. Regional tissue volume is traditionally measured for the purposes of HILP using water displacement volumetry (WDV). Although this technique is considered the gold standard, it is time-consuming and complicated to implement, especially in obese and elderly patients. AIM: The aim of the present study was to compare the different methods described in the literature for calculating regional tissue volume in the HILP setting, and to validate an open source software. METHODS: We reviewed the charts of 22 patients (11 males and 11 females) who had non-disseminated melanoma with in-transit metastases or sarcoma of the lower limb. We calculated the volume of the limb using four different methods: WDV, tape measurements and segmentation of computed tomography images using Osirix and Oncentra Masterplan softwares. RESULTS AND CONCLUSION: The overall comparison provided a concordance correlation coefficient (CCC) of 0.92 for the calculations of whole limb volume. In particular, when Osirix was compared with Oncentra (validated for volume measures and used in radiotherapy), the concordance was near-perfect for the calculation of the whole limb volume (CCC = 0.99). With methods based on CT the user can choose a reliable plane for segmentation purposes. CT-based methods also provides the opportunity to separate the whole limb volume into defined tissue volumes (cortical bone, fat and water). PMID- 27005885 TI - Infection prevention in breast implant surgery - A review of the surgical evidence, guidelines and a checklist. AB - INTRODUCTION: As a result of increasing use of implant-based breast reconstruction, complications such as infection are being encountered more frequently. Surgical Site Infections (SSIs) cause morbidity for the patient, can lead to capsular contracture or implant loss and are costly to healthcare systems. National Guidelines suggesting methods to reduce SSI related complications have been produced, but are limited in the scope of interventions covered and underlying evidence presented. METHODS: We performed a literature review encompassing a wide variety of possible SSI prevention strategies. We aimed to present summaries of the available evidence and give pragmatic recommendations as to their validity to use as guidelines for infection prevention strategies for implant-based breast reconstruction. RESULTS: A lack of high quality data relating to the benefit of SSI prevention strategies in implant based breast reconstruction exists. Many papers relate to orthopaedic implant surgery, or clean surgery in general. Following review of the evidence, sufficient data exists to support use of perioperative antibiotics at implant based breast reconstruction, with continuation for an extended period in "high risk" patients. Alcohol containing skin preparations should be used over aqueous solutions. Laminar air flow use is suggested. Theatre traffic should be kept to a minimum, as should duration of operative procedure. The implant pocket should be washed prior to implantation. Double gloving and conductive warming are also endorsed. CONCLUSIONS: We have produced a perioperative "Theatre Implant Checklist" for SSI prevention in implant-based breast surgery, with a set of pragmatic up to date guidelines, which allows the reader to evaluate the evidence upon which our recommendations are based. PMID- 27005887 TI - Evaluating the impact of a quality care-metric on public health nursing practice: protocol for a mixed methods study. AB - AIM: To establish, implement and evaluate the impact of a quality care-metric developed to measure public health nursing practice. BACKGROUND: Measurement of care practices plays an integral role in quality improvement and promotes positive change in healthcare delivery. Quality care-metrics has been identified as a means of effectively measuring public health nursing practice. Public health nurses in Ireland are 'all-purpose' generalist community-based nurses caring for people across the lifespan, in defined geographical areas, employed by the Health Service Executive. In the public health nurse's child and maternal health role, the 'primary visit' (postnatal visit) has been identified as the most important contact a public health nurse has with a mother and her new baby. DESIGN: Mixed methods using a sequential multiphase design. METHODS: This study involves three phases. The first phase will include focus group and individual interviews with key healthcare professionals and new mothers, using purposively chosen sampling. Thematic analysis of data will identify key components for the development of a quality care-metric. Phase two will be a RAND appropriateness survey with a panel of experts, to develop and validate the quality care-metric. The third phase will involve implementation and evaluation of the quality care-metric. Descriptive and inferential statistics will be completed using SPSS version 21. Funding for this research study was approved in December 2013. CONCLUSION: This study will evaluate the impact of introducing a quality care-metric into public health nursing practice. Results will illuminate the quality of public health nursing practice in relation to the primary visit. PMID- 27005886 TI - Integrating Epitaxial-Like Pb(Zr,Ti)O3 Thin-Film into Silicon for Next-Generation Ferroelectric Field-Effect Transistor. AB - The development of ferroelectric random-access memory (FeRAM) technology with control of grain boundaries would result in a breakthrough for new nonvolatile memory devices. The excellent piezoelectric and electrical properties of bulk ferroelectrics are degraded when the ferroelectric is processed into thin films because the grain boundaries then form randomly. Controlling the nature of nucleation and growth are the keys to achieving a good crystalline thin-film. However, the sought after high-quality ferroelectric thin-film has so far been thought to be impossible to make, and research has been restricted to atomic layer deposition which is extremely expensive and has poor reproducibility. Here we demonstrate a novel epitaxial-like growth technique to achieve extremely uniform and large rectangular-shaped grains in thin-film ferroelectrics by dividing the nucleation and growth phases. With this technique, it is possible to achieve 100-MUm large uniform grains, even made available on Si, which is large enough to fabricate a field-effect transistor in each grain. The electrical and reliability test results, including endurance and retention test results, were superior to other FeRAMs reported so far and thus the results presented here constitute the first step toward the development of FeRAM using epitaxial-like ferroelectric thin-films. PMID- 27005888 TI - Investigation of Acidithiobacillus ferrooxidans in pure and mixed-species culture for bioleaching of Theisen sludge from former copper smelting. AB - AIMS: The aim of this study was to investigate the potential of bioleaching for the treatment of an environmentally hazardous waste, a blast-furnace flue dust designated Theisen sludge. METHODS AND RESULTS: Bioleaching of Theisen sludge was investigated at acidic conditions with Acidithiobacillus ferrooxidans in pure and mixed-species culture with Acidiphilium. In shaking-flask experiments, bioleaching parameters (pH, redox potential, zinc extraction from ZnS, ferrous- and ferric-iron concentration) were controlled regularly. The analysis of the dissolved metals showed that 70% zinc and 45% copper were extracted. Investigations regarding the arsenic and antimony species were performed. When iron ions were lacking, animonate (Sb(V)) and total arsenic concentration were highest in solution. The bioleaching approach was scaled up in stirred-tank bioreactors resulting in higher leaching efficiency of valuable trace elements. Concentrations of dissolved antimony were approx. 23 times, and of cobalt, germanium, and rhenium three times higher in comparison to shaking-flask experiments, when considering the difference in solid load of Theisen sludge. CONCLUSIONS: The extraction of base and trace metals from Theisen sludge, despite of its high content of heavy metals and organic compounds, was feasible with iron oxidizing acidophilic bacteria. In stirred-tank bioreactors, the mixed-species culture performed better. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this study is the first providing an appropriate biological technology for the treatment of Theisen sludge to win valuable elements. PMID- 27005889 TI - Treatment of Internet Addiction with Anxiety Disorders: Treatment Protocol and Preliminary Before-After Results Involving Pharmacotherapy and Modified Cognitive Behavioral Therapy. AB - BACKGROUND: The growth of the Internet has led to significant change and has become an integral part of modern life. It has made life easier and provided innumerous benefits; however, excessive use has brought about the potential for addiction, leading to severe impairments in social, academic, financial, psychological, and work domains. Individuals addicted to the Internet usually have comorbid psychiatric disorders. Panic disorder (PD) and generalized anxiety disorder (GAD) are prevalent mental disorders, involving a great deal of damage in the patient's life. OBJECTIVE: This open trial study describes a treatment protocol among 39 patients with anxiety disorders and Internet addiction (IA) involving pharmacotherapy and modified cognitive behavioral therapy (CBT). METHODS: Of the 39 patients, 25 were diagnosed with PD and 14 with GAD, in addition to Internet addiction. At screening, patients responded to the MINI 5.0, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Clinical Global Impressions Scale, and the Young Internet Addiction Scale. At that time, IA was observed taking into consideration the IAT scale (cutoff score above 50), while anxiety disorders were diagnosed by a psychiatrist. Patients were forwarded for pharmacotherapy and a modified CBT protocol. Psychotherapy was conducted individually, once a week, over a period of 10 weeks, and results suggest that the treatment was effective for anxiety and Internet addiction. RESULTS: Before treatment, anxiety levels suggested severe anxiety, with an average score of 34.26 (SD 6.13); however, after treatment the mean score was 15.03 (SD 3.88) (P<.001). A significant improvement in mean Internet addiction scores was observed, from 67.67 (SD 7.69) before treatment, showing problematic internet use, to 37.56 (SD 9.32) after treatment (P<.001), indicating medium Internet use. With respect to the relationship between IA and anxiety, the correlation between scores was .724. CONCLUSIONS: This study is the first research into IA treatment of a Brazilian population. The improvement was remarkable due to the complete engagement of patients in therapy, which contributed to the success of the treatment from a behavioral perspective, and gave patients the confidence to continue to manage Internet use in their lives. PMID- 27005891 TI - Endometriotic mesenchymal stem cells significantly promote fibrogenesis in ovarian endometrioma through the Wnt/beta-catenin pathway by paracrine production of TGF-beta1 and Wnt1. AB - STUDY QUESTION: Are endometriotic mesenchymal stem cells (Ecto-MSCs) involved in the fibrosis of ovarian endometrioma? SUMMARY ANSWER: Ecto-MSCs enhanced the fibrotic behavior of stromal cells in ovarian endometrioma through the Wnt/beta catenin pathway by paracrine production of transforming growth factor-beta1 (TGF beta1) and Wnt1. WHAT IS KNOWN ALREADY: Endometriosis is characterized by ectopic outgrowth of endometrial stroma and glands surrounded by dense fibrous tissues. The pathogenesis of endometriosis, especially ovarian endometrioma-associated fibrosis, is still unknown. STUDY DESIGN, SIZE, DURATION: We analyzed endometrial samples from 15 patients of reproductive age with ovarian endometrioma and normal menstrual cycles. A total of 54 nude mice received a single injection of proliferative endometrial fragments from 14 individuals without endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Conditioned medium (CM) was collected from endometrial mesenchymal stem cells (Euto-MSCs) and Ecto-MSCs. The effects of CM on cell proliferation, migration, invasion and collagen gel contraction of endometrial and endometriotic stromal cells (Euto- and Ecto-ESCs) in ovarian endometrioma were evaluated by cell counting kit-8, transwell and collagen gel contraction assays. Effects of CM on fibrotic markers' expression [including alpha-smooth muscle actin, Type I collagen, connective tissue growth factor and fibronectin (FN)] in Euto- and Ecto-ESCs were determined by real-time reverse transcription-polymerase chain reaction and western blotting. Additionally, fibrogenic effects of Ecto-MSC CM treatment on endometriotic implants were analyzed using a xenograft model of endometriosis in immunodeficient nude mice. MAIN RESULTS AND THE ROLE OF CHANCE: Our results demonstrated that Ecto-MSC CM significantly promoted cell proliferation, migration, invasion and collagen gel contraction of Euto- and Ecto-ESCs from patients with ovarian endometrioma compared with control and Euto-MSC CM. Expression levels of fibrotic markers in Euto- and Ecto-ESCs were dramatically elevated after treatment with Ecto-MSC CM. Ecto-MSCs secreted higher levels of TGF-beta1 and Wnt1 compared with Euto-MSCs. Furthermore, both TGF-beta1 and Wnt1 significantly increased expression of fibrotic markers in Euto- and Ecto-ESCs, which was reversed by an anti-TGF-beta1 antibody or Wnt1 negative regulator, Dickkopf-related protein 1 (Dkk1). Mechanistic studies demonstrated that Wnt/beta-catenin signaling pathways in stromal cells were activated by Ecto-MSC CM. Animal experiments showed that TGF beta1 and Wnt1 as well as Ecto-MSC CM markedly increased the expression of FN and collagen I, which enhanced the progression of fibrosis in endometriosis. LIMITATIONS, REASONS FOR CAUTION: To our knowledge, this is the first study to identify the role of Ecto-MSCs in the pathogenesis of fibrosis in ovarian endometrioma. However, numerous other growth factors and cell types may also be involved in the pathogenesis. Therefore, further studies are required to elucidate the paracrine effects of cells in ovarian endometrioma. WIDER IMPLICATIONS OF THE FINDINGS: Ecto-MSCs may be involved in the pathogenesis of fibrosis in ovarian endometrioma. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by the National Natural Science Foundation of China (81471505 and 81270657). No competing interests are declared. PMID- 27005890 TI - Endometrial vezatin and its association with endometriosis risk. AB - STUDY QUESTION: Do endometriosis risk-associated single nucleotide polymorphisms (SNPs) found at the 12q22 locus have effects on vezatin ( ITALIC! VEZT) expression? SUMMARY ANSWER: The original genome-wide association study (GWAS) SNP (rs10859871), and other newly identified association signals, demonstrate strong evidence for ITALIC! cis-expression quantitative trait loci (eQTL) effects on ITALIC! VEZT expression. WHAT IS KNOWN ALREADY: GWAS have identified several disease-risk loci (SNPs) associated with endometriosis. The SNP rs10859871 is located within the ITALIC! VEZT gene. ITALIC! VEZT expression is altered in the endometrium of endometriosis patients and is an excellent candidate for having a causal role in endometriosis. Most of the SNPs identified from GWAS are not located within the coding region of the genome. However, they are likely to have an effect on the regulation of gene expression. Genetic variants that affect levels of gene expression are called expression quantitative trait loci (eQTL). STUDY DESIGN, SIZE, DURATION: Samples for genotyping and ITALIC! VEZT variant screening were drawn from women recruited for genetic studies in Australia/New Zealand and women undergoing surgery in a tertiary care centre. Coding variants for ITALIC! VEZT were screened in blood from 100 unrelated individuals (endometriosis-dense families) from the QIMR Berghofer Medical Research Institute dataset. SNPs at the 12q22 locus were imputed and reanalysed for their association with endometriosis. Reanalysis of endometriosis risk-association was performed on a final combined Australian dataset of 2594 cases and 4496 controls. Gene expression was performed on 136 endometrial samples. eQTL analysis in whole blood was performed on 862 individuals from the Brisbane Systems Genetics Study. Endometrial tissue-specific eQTL analysis was performed on 122 samples (eutopic endometrium) collected following laparoscopic surgery. VEZT protein expression studies employed ITALIC! n = 56 (western blotting) and ITALIC! n = 42 (immunohistochemistry) endometrial samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: The women recruited for this study provided blood and/or endometrial tissue samples in a hospital setting. Genomic DNA was screened for common and coding variants. SNPs of interest in the 12q22 region were genotyped using Agena MassARRAY technology or Taqman SNP genotyping assay. Gene expression profiles from RNA extracted from blood and endometrial tissue samples were generated using Illumina whole-genome expression chips (Human HT-12 v4.0). Whole protein extracted from endometrium was used for VEZT western blots, and paraffin sections of endometrium were employed for VEZT immunohistochemistry semi-quantitative analysis. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 11 coding variants of ITALIC! VEZT (including one novel variant) were identified from an endometriosis dense cohort. Polymorphic coding and imputed SNPs were combined with previous GWAS data to reanalyse the endometriosis risk association of the 12q22 region. The disease association signal at 12q22 was due to coding variants in ITALIC! VEZT or ITALIC! FGD6 (FYVE, RhoGEF and PH domain-containing 6) and SNPs with the strongest signals were either intronic or intergenic. We found strong evidence for ITALIC! VEZT cis-eQTLs with the sentinel SNP (rs10859871) in blood and endometrium, where the endometriosis risk allele (C) was associated with an increase in ITALIC! VEZT expression. We could not demonstrate this genotype specific effect on VEZT protein expression in endometrium. However, we did observe a menstrual cycle stage specific increase in VEZT protein expression in endometrial glands, specific to the secretory phase ( ITALIC! P = 2.0 * 10(-4)). LIMITATIONS, REASONS FOR CAUTION: In comparison to the blood sample datasets, the study numbers of endometrial tissues were substantially reduced. Protein studies failed to complement RNA results, also likely a reflection of the low study numbers in these experiments. ITALIC! In silico prediction tools used in this investigation are typically based on cell lines different to our tissues of interest, thus any functional annotations drawn from these approaches should be considered carefully. Therefore, functional studies on VEZT and related pathway components are still warranted to unequivocally implicate a causal role for VEZT in endometriosis pathophysiology. WIDER IMPLICATIONS OF THE FINDINGS: GWAS have proven to be very valuable tools for deciphering complex diseases. Endometriosis is a text-book example of a complex disease, involving genetic, lifestyle and environmental influences. Our focused investigation of the 12q22 region validates an association with increased endometriosis risk. Endometriosis risk SNPs (including rs10859871) located within this locus demonstrated evidence for ITALIC! cis-eQTLs on ITALIC! VEZT expression. By examining women who possess an enhanced genetic risk of developing endometriosis, we have identified an effect on ITALIC! VEZT expression and therefore a potential gene/gene pathway in endometriosis disease establishment and development. STUDY FUNDING/COMPETING INTERESTS: Funding for this work was provided by NHMRC Project Grants GNT1012245, GNT1026033, GNT1049472 and GNT1046880. G.W.M. is supported by the NHMRC Fellowship scheme (GNT1078399). S.J.H.-C. is supported by the J.N. Peters Bequest Fellowship. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A. PMID- 27005892 TI - Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study. AB - STUDY QUESTION: Could cell therapy using autologous peripheral blood CD133+ bone marrow-derived stem cells (BMDSCs) offer a safe and efficient therapeutic approach for patients with refractory Asherman's syndrome (AS) and/or endometrial atrophy (EA) and a wish to conceive? SUMMARY ANSWER: In the first 3 months, autologous cell therapy, using CD133+ BMDSCs in conjunction with hormonal replacement therapy, increased the volume and duration of menses as well as the thickness and angiogenesis processes of the endometrium while decreasing intrauterine adhesion scores. WHAT IS KNOWN ALREADY: AS is characterized by the presence of intrauterine adhesions and EA prevents the endometrium from growing thicker than 5 mm, resulting in menstruation disorders and infertility. Many therapies have been attempted for these conditions, but none have proved effective. STUDY DESIGN, SIZE, DURATION: This was a prospective, experimental, non-controlled study. There were 18 patients aged 30-45 years with refractory AS or EA were recruited, and 16 of these completed the study. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and neoangiogenesis were assessed before and 3 and 6 months after cell therapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: After the initial hysteroscopic diagnosis, BMDSC mobilization was performed by granulocyte-CSF injection, then CD133+ cells were isolated through peripheral blood aphaeresis to obtain a mean of 124.39 million cells (range 42-236), which were immediately delivered into the spiral arterioles by catheterization. Subsequently, endometrial treatment after stem cell therapy was assessed in terms of restoration of menses, endometrial thickness (by vaginal ultrasound), adhesion score (by hysteroscopy), neoangiogenesis and ongoing pregnancy rate. The study was conducted at Hospital Clinico Universitario of Valencia and IVI Valencia (Spain). MAIN RESULTS AND THE ROLE OF CHANCE: All 11 AS patients exhibited an improved uterine cavity 2 months after stem cell therapy. Endometrial thickness increased from an average of 4.3 mm (range 2.7-5) to 6.7 mm (range 3.1-12) ( ITALIC! P = 0.004). Similarly, four of the five EA patients experienced an improved endometrial cavity, and endometrial thickness increased from 4.2 mm (range 2.7-5) to 5.7 mm (range 5-12) ( ITALIC! P = 0.03). The beneficial effects of the cell therapy increased the mature vessel density and the duration and intensity of menses in the first 3 months, with a return to the initial levels 6 months after the treatment. Three patients became pregnant spontaneously, resulting in one baby boy born, one ongoing pregnancy and a miscarriage. Furthermore, seven pregnancies were obtained after fourteen embryo transfers, resulting in three biochemical pregnancies, one miscarriage, one ectopic pregnancy, one baby born and one ongoing pregnancy. LIMITATIONS, REASONS FOR CAUTION: Limitations of this pilot study include the small sample size and the lack of control group. WIDER IMPLICATIONS OF THE FINDINGS: This novel autologous cell therapy is a promising therapeutic option for patients with these incurable pathologies and a wish to conceive. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Spanish Ministry of Science and Innovation (SAF 2012-31017, Principal Investigator C.S.), Spanish Ministry of Health (EC11-299, Principal Investigator C.S.) and Regional Valencian Ministry of Education (PROMETEOII/2013/018, Principal Investigator C.S.). Four authors (X.S., I.C., A.P. and C.S.) are co-inventors of the patent resulting from this work (Application number: 62/013,121). S.C., C.A., F.R., J.F., J.P. and J.R. have no conflict of interest in relation to this work. TRIAL REGISTRATION NUMBER: This study was registered with ClinicalTrials.gov (NCT02144987). PMID- 27005893 TI - What is the optimal duration of progesterone administration before transferring a vitrified-warmed cleavage stage embryo? A randomized controlled trial. AB - STUDY QUESTION: What is the impact on clinical pregnancy rates when vitrified cleavage stage Day 3 embryos, warmed and cultured overnight to Day 4, are transferred on the 3rd or 5th day of progesterone administration in an artificial cycle? SUMMARY ANSWER: Clinical pregnancy rates are similar when transferring a vitrified-warmed cleavage stage Day 3 embryo after overnight culture on the 3rd or 5th day of progesterone administration. WHAT IS KNOWN ALREADY: In artificially prepared cycles, progesterone supplementation is generally started 3 days before embryo transfer, although the optimal length of exposure to progesterone before frozen embryo transfer (FET) has not been established. However, in a natural cycle, serum progesterone levels start to rise before ovulation, due to the LH stimulated production by the peripheral granulosa cells. Hence, it could be postulated that progesterone supplementation before embryo transfer in an artificial cycle should start earlier or even later. STUDY DESIGN, SIZE, DURATION: Prospective, randomized controlled trial, encompassing 300 patients who had embryos frozen on Day 3 and who underwent FET in an artificial cycle. Between 1 November 2012 and 31 December 2014, 300 patients were allocated to one of two groups as soon as endometrial thickness reached >=7 mm on ultrasound after estrogen supplementation. A computer-generated randomization list was used, not concealed to the physicians. Each patient was enrolled into the study only once. FET was performed on the fifth day of progesterone supplementation in Group A, whereas in Group B, FET was performed on the third day of vaginal micronized progesterone administration. Embryos were thawed the day before transfer and after overnight culture, one or two Day 4 embryos were transferred. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and fifty patients in Group A received 5 days of vaginal micronized progesterone tablets and one hundred and fifty patients in Group B received 3 days of micronized progesterone vaginally before FET. In Group A, 13 patients did not have an embryo transfer, compared with 12 patients in Group B. MAIN RESULTS AND THE ROLE OF CHANCE: Clinical pregnancy rates did not differ significantly between both groups (37/137 (27.0%) in Group A versus 26/138 (18.8%) in Group B (OR 1.6 (CI 0.9-2.82), ITALIC! P = 0.11). However, early pregnancy loss was significantly higher in Group B (32/58 (55.2%)) compared with Group A (21/58 (36.2%)) (OR 0.46 (CI 0.22-0.97), ITALIC! P = 0.04). LIMITATIONS, REASONS FOR CAUTION: Although no statistically significant difference was seen in the primary outcome, the study may have been underpowered to detect smaller differences. The study was also not blinded and patients were aware of the exact duration of progesterone supplementation. WIDER IMPLICATIONS OF THE FINDINGS: This is the first randomized controlled trial to show that duration of progesterone administration in an artificially prepared FET cycle may modulate cycle outcome and that too short progesterone supplementation might be deleterious. STUDY FUNDING/COMPETING INTERESTS: No external finance was involved in this study. All authors declare to have no conflict of interest with regard to this trial. TRIAL REGISTRATION NUMBER: The trial was registered at clinicaltrials.gov (NCT01940653). TRIAL REGISTRATION DATE: 9 September 2013. DATE OF FIRST PATIENT'S ENROLLMENT: 1 November 2012. PMID- 27005894 TI - Balance between von Willebrand factor and ADAMTS13 following major partial hepatectomy. AB - BACKGROUND: Conventional coagulation tests are frequently prolonged after liver surgery, suggesting a postoperative bleeding tendency. At the same time, thrombotic complications following partial hepatectomy (PH) are not uncommon. Little is known about changes in the platelet adhesive protein von Willebrand factor (VWF) and its cleaving protease a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13) following a PH. METHODS: Plasma samples were collected before and after PH and pylorus-preserving pancreaticoduodenectomy (PPPD), and from 24 healthy individuals. Plasma levels of VWF and ADAMTS13, VWF activity and VWF-dependent platelet adhesion were measured, and compared between the groups. RESULTS: Median (i.q.r.) VWF levels increased more after PH (17 patients) than following PPPD (10), reaching the highest level on postoperative day (POD) 3 (570 (473-656) versus 354 (305-476) per cent respectively; P = 0.009). VWF levels remained raised on POD 30. A decrease in median (i.q.r.) ADAMTS13 activity was observed for both patient groups, reaching the lowest level on POD 7 (24 (16-32) versus 38 (23-66) per cent for PH and PPPD respectively; P = 0.049), and levels remained significantly reduced at POD 30. VWF activity was significantly higher on day 7 following PH compared with PPPD (median (i.q.r.) 517 (440-742) versus 385 (322-484) per cent respectively; P = 0.009), and remained increased at POD 30. VWF-dependent platelet adhesion under conditions of flow was increased until POD 30 in patients after PH and PPPD, but was more pronounced in the PH group. CONCLUSION: There are changes in the balance between VWF and ADAMTS13 levels and activity in patients after both PH and PPPD. Changes in the VWF-ADAMTS13 axis were more pronounced and of longer duration after PH than following PPPD. PMID- 27005895 TI - [Assessment of control of cardiovascular risk factors in obese posmenopausal women after monitoring a structured dietary education and exercise program. (SISIFO Program)]. AB - OBJECTIVE: Evaluate the influence of a specific program of physical exercise on cardiovascular risk, quality of life and eating habits of menopausal women. METHOD: Prospective, intervention study previous-after without control group for three months. 66 menopausal women were included. The intervention consisted of a structured diet and exercise program. Biochemical, anthropometric, dietary and life quality parameters were determined before and three months after surgery. RESULTS: After the intervention a decrease in weight (4.4+/-2,3kg) and BMI (1.83+/-0.84kg/m(2)) (p<.05) occurs. A decrease in SBP (p<.05) was also observed. The fasting glucose went down 13.75+/-11.11mg/dl and HbA1c fell by 0.19+/-0,12%, both with p<.05. The lipid profile follows a similar behavior, highlighting a decline of 8+/- 6.2mg/dl in LDL cholesterol values (p<.05). The score on the measured cardiovascular risk by the Framingham tables decreases by 3% postoperatively (p<.05). Regarding the quality of life, it is significantly improved in all analyzed areas. CONCLUSIONS: The application of a structured exercise and diet program improves close monitoring parameters associated with cardiovascular risk of the women studied. It also improves the quality of life and dietary habits. PMID- 27005896 TI - Glycaemic control status among type 2 diabetic patients and the role of their diabetes coping behaviours: a clinic-based study in Tripoli, Libya. AB - BACKGROUND: Achieving good glycaemic control is important in diabetes management. However, poor glycaemic control is widely reported. This article assessed the prevalence of uncontrolled and poor glycaemic control among Libyans with type 2 diabetes and examined the relative contribution of diabetes coping behaviours to their glycaemic control status. METHODS: A cross-sectional study was undertaken in 2013 in a large diabetes centre in Tripoli. The study included 523 respondents. Diabetes coping behaviours were measured using the revised version of the Summary of Diabetes Self-Care Activities measure (SDSCA) and the eight item Morisky Medication Adherence Scale (MMAS-8((c))), while glycaemic control status was based on the HbA1c level. RESULTS: Mean HbA1c was 8.9 (+/-2.1), and of the 523 patients, only 114 (21.8%) attained the glycaemic control target of HbAc1 of less than 7.0%. Females (OR=1.74, 95% CI=1.03-2.91), patients on insulin and oral hypoglycaemic agents (OR=1.92, 95% CI=1.05-3.54), patients on insulin (OR=3.14, 95% CI=1.66-6.03), and low-medication adherents (OR=2.25, 95% CI=1.36 3.73) were more likely to have uncontrolled and poor glycaemic control, while exercise contributed to glycaemic control status as a protective factor (OR=0.85, 95% CI=0.77-0.94). CONCLUSION: The findings from this study showed the considerable burden of uncontrolled and poor glycaemic control in one of the largest diabetes care settings in Libya. Medication adherence as well as exercise promotion programs would help in reducing the magnitude of poor glycaemic control. PMID- 27005897 TI - Increased ventro-medial prefrontal activations in schizophrenia smokers during cigarette cravings. AB - BACKGROUND: Highly prevalent in schizophrenia, tobacco smoking substantially increases the risk of cardiac-related death. Compared to the general population, tobacco smoking cessation rates are lower in schizophrenia. Unfortunately, the reasons for these low cessation rates remain poorly understood. Recently, it has been shown that tobacco cravings are increased in schizophrenia smokers compared to smokers with no comorbid psychiatric disorder. In view of these results, we sought to examine - for the first time - the neurophysiologic responses elicited by cigarette cues in schizophrenia smokers. We hypothesized that cigarettes cues would elicit increased activations in brain regions involved in drug cravings in schizophrenia smokers relative to control smokers. METHODS: Smokers with (n=18) and without (n=24) schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging (fMRI) while viewing appetitive cigarette images. RESULTS: Schizophrenia smokers and smokers with no psychiatric comorbidity did not differ in subjective cravings in response to appetitive smoking cues. However, in schizophrenia smokers relative to control smokers, we found that appetitive cigarette cues triggered increased activations of the bilateral ventro medial prefrontal cortex, a core region of the brain reward system. Moreover, a negative correlation was observed between cigarette cravings and activations of the right ventro-medial prefrontal cortex in schizophrenia smokers. DISCUSSION: The current results highlight a key role of the brain reward system in cigarette craving in schizophrenia, and suggest that the neurophysiologic mechanisms involved in the regulation of cue-induced cigarette craving are impaired in this population. PMID- 27005898 TI - NF-kappaB/Rel, not STAT5, regulates nitric oxide synthase transcription in Apostichopus japonicus. AB - Nitric oxide (NO) is an important signaling molecular in the immune system of all vertebrates and invertebrates for pathologic and physiologic process, and it is largely produced by inducible nitric oxide synthase (iNOS). To uncover key mechanisms regulating NOS expression in sea cucumber Apostichopus japonicus, we amplified a fragment of the NOS promoter by genome walking approach and characterized putative transcription factor binding motifs using luciferase assay. Transient transfection of EPC cells using 5'-deletion constructs linked to luciferase reporter revealed that the region -614/+39 contributed importantly to expression of the AjNOS gene, and the -614 bp of the 5'-flanking region of the AjNOS gene responded well to LPS. Analysis of the functional promoter region revealed the presence of two potential NF-kappaB (-375 bp to -366 bp, -76 bp to 67 bp) and three STAT binding sites (-284 bp to -276 bp, -95 bp to 87 bp, -81 bp to -73 bp). When luciferase reporter vector and expression vector co-transfected revealed that NF-kappaB/Rel, but not STAT5, activate the AjNOS promoter fragment. Furthermore, two truncated reporter vectors co-transfected with vector expressing NF-kappaB/Rel revealed that the first NF-kappaB binding site (-375 bp to -366 bp) was essential for the ability of this promoter to induce AjNOS transcription. In addition, blocking the AjRel by SN50 (NF-kappaB inhibitory peptide) depressed the AjNOS expression and NO production both in vivo and in vitro, respectively, revealing that AjRel might directly modulate AjNOS. All our findings confirmed that NF-kappaB dependent mechanisms regulating expression of AjNOS and suggested a means of linking NO production to the immune response. PMID- 27005899 TI - Emerging role of microRNAs in regulating macrophage activation and polarization in immune response and inflammation. AB - Diversity and plasticity are hallmarks of macrophages. Classically activated macrophages are considered to promote T helper type 1 responses and have strong microbicidal, pro-inflammatory activity, whereas alternatively activated macrophages are supposed to be associated with promotion of tissue remodelling and responses to anti-inflammatory reactions. Transformation of different macrophage phenotypes is reflected in their different, sometimes even opposite, roles in various diseases or inflammatory conditions. MicroRNAs (miRNAs) have emerged as critical regulators of macrophage polarization (MP). Several miRNAs are induced by Toll-like receptors signalling in macrophages and target the 3' untranslated regions of mRNAs encoding key molecules involved in MP. Therefore, identification of miRNAs related to the dynamic changes of MP and understanding their functions in regulating this process are important for discussing the molecular basis of disease progression and developing novel miRNA-targeted therapeutic strategies. Here, we review the current knowledge of the role of miRNAs in MP with relevance to immune response and inflammation. PMID- 27005900 TI - A Novel Supra-Brow Combined with Infra-Brow Lift Approach for Asian Women. AB - BACKGROUND: Direct brow lift surgery remains popular among Asian women despite its disadvantages. The traditional direct brow lift by a supra-brow incision is not suitable for Asian women because of their unique facial features, such as higher eyebrows, wider upper eyelids, and more orbital fat. Therefore, we designed a novel brow lift technique via a supra-brow combined with an infra-brow approach for Asian women. METHODS: An area of skin above and below the eyebrow was measured, demarcated, and surgically removed. The redundant orbicularis oculi muscle (OOM) was excised while keeping the frontalis muscle intact. The OOM in the inferior flap was elevated and sutured to the frontalis muscle. In cases of puffy eyelids, orbital fat was partially removed through an infra-brow incision. Finally, a series of modifications were performed to reduce post-operative scarring. RESULTS: A total of 496 patients underwent this surgery from July 2009 to December 2013 and 432 patients were followed up for at least 6 months after surgery. Post-operative scars, in most patients (428/432), were inconspicuous. There were no facial nerve injuries documented and eight patients reported transient forehead numbness. The height of the palpebral fissure was increased but there was no marked increase observed of the distance between the upper eyelid edge and the eyebrow. In follow-up visits, 409 out of 432 patients (94.7 %) were satisfied with their surgical results. CONCLUSIONS: This new brow lift technique via a supra-brow combined with an infra-brow approach provided a simple and safe surgical repair of lateral brow ptosis, upper eyelids hooding, and crows' feet in Asian women. The surgical outcomes were predictable and the scars were inconspicuous. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27005901 TI - Reducing the psychosocial impact of aphasia on mood and quality of life in people with aphasia and the impact of caregiving in family members through the Aphasia Action Success Knowledge (Aphasia ASK) program: study protocol for a randomized controlled trial. AB - BACKGROUND: People with aphasia and their family members are at high risk of experiencing post stroke depression. The impact of early interventions on mood and quality of life for people with aphasia is unknown. METHODS/DESIGN: This study will determine whether an early intervention for both the person with aphasia after stroke and their family members leads to better mood and quality of life outcomes for people with aphasia, and less caregiver burden and better mental health for their family members. This is a multicenter, cluster-randomized controlled trial. Clusters, which are represented by Health Service Districts, will be randomized to the experimental intervention (Aphasia Action Success Knowledge Program) or an attention control (Secondary Stroke Prevention Information Program). People with aphasia and their family members will be blinded to the study design and treatment allocation (that is, will not know there are two arms to the study). Both arms of the study will receive usual care in addition to either the experimental or the attention control intervention. A total of 344 people with aphasia and their family members will be recruited. Considering a cluster size of 20, the required sample size can be achieved from 18 clusters. However, 20 clusters will be recruited to account for the potential of cluster attrition during the study. Primary outcome measures will be mood and quality of life of people with aphasia at 12 months post stroke. Secondary measures will be family member outcomes assessing the impact of caregiving and mental health, and self-reported stroke risk-related behaviors of people with aphasia. DISCUSSION: This is the first known program tailored for people with aphasia and their family members that aims to prevent depression in people with aphasia by providing intervention early after the stroke. TRIAL REGISTRATION: This trial is registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) as ACTRN12614000979651 . Date registered: 11 September 2014. PMID- 27005902 TI - A Meta-Analysis of Factors Influencing the Development of Trust in Automation: Implications for Understanding Autonomy in Future Systems. AB - OBJECTIVE: We used meta-analysis to assess research concerning human trust in automation to understand the foundation upon which future autonomous systems can be built. BACKGROUND: Trust is increasingly important in the growing need for synergistic human-machine teaming. Thus, we expand on our previous meta-analytic foundation in the field of human-robot interaction to include all of automation interaction. METHOD: We used meta-analysis to assess trust in automation. Thirty studies provided 164 pairwise effect sizes, and 16 studies provided 63 correlational effect sizes. RESULTS: The overall effect size of all factors on trust development was g = +0.48, and the correlational effect was [Formula: see text] = +0.34, each of which represented medium effects. Moderator effects were observed for the human-related (g = +0.49; [Formula: see text] = +0.16) and automation-related (g = +0.53; [Formula: see text] = +0.41) factors. Moderator effects specific to environmental factors proved insufficient in number to calculate at this time. CONCLUSION: Findings provide a quantitative representation of factors influencing the development of trust in automation as well as identify additional areas of needed empirical research. APPLICATION: This work has important implications to the enhancement of current and future human automation interaction, especially in high-risk or extreme performance environments. PMID- 27005904 TI - A comparison of a short versus a conventional femoral cementless stem in total hip arthroplasty in patients 70 years and older. AB - BACKGROUND: The aim of this study was to compare clinical and radiological outcomes between a short femoral cementless stem and a conventional femoral cementless stem in total hip arthroplasty in patients 70 years and older. METHODS: From December 2011 and July 2013, we retrospectively reviewed 50 patients (55 hips) 70 years and older treated with a short femoral cementless stem and 53 patients (58 hips) 70 years and older treated with a conventional femoral cementless stem. Their mean age was 74 +/- 13.2 years and 75 +/- 10.4 years, respectively. The mean follow-up was 40 +/- 3.6 months and 42 +/- 5.2 month, respectively. They were pre- and postoperatively evaluated by the clinical and radiological examination. RESULTS: There was no difference in terms of average operative time, average estimated blood loss, and average hemoglobin at discharge between the short stem and the conventional stem. No patients with the short stem had intra-operative fracture, but five patients with the conventional stem had intra-operative fracture. At final follow-up, there was no statistically significant difference in Harris Hip Score, and radiographic review level between two stems. No hip with the short stem had thigh pain, but six hips with the conventional stem had thigh pain at the final follow-up. No component was revised for aseptic loosening in either group. CONCLUSIONS: Our study demonstrated that both short cementless stem and conventional cementless stem provided stable fixation and achieved a satisfactory result in patients 70 years and older and the short cementless stem had a low incidence of thigh pain and intra-operative fracture. PMID- 27005905 TI - The Emergence of Theileria parva in Jonglei State, South Sudan: Confirmation Using Molecular and Serological Diagnostic Tools. AB - A cross-sectional survey was carried out in four counties of Jonglei State, South Sudan, between May and June 2012 to determine the distribution and northern limit of Theileria parva, the causative agent of East Coast fever in cattle, and its tick vector Rhipicephalus appendiculatus, as a prerequisite to the deployment of relevant control strategies. A total of 1636 ticks, 386 serum samples and 399 blood samples were collected from indigenous, apparently healthy, cattle of different age groups. Tick species were identified morphologically, and the identity of R. appendiculatus was confirmed by DNA barcoding. Overall, the T. parva infection rate in R. appendiculatus was 25% as shown by nested PCR. ELISA was used to assess antibodies to T. parva, and the overall seroprevalence was 22.8%. PCR of the blood samples showed 55 (13.8%) were positive for T. parva. This is the first molecular confirmation of T. parva DNA in areas north of Juba, where it was previously known and established. The northern limit of T. parva was determined as N006.17.792, about 242 Km north from Juba. Implication of this limit on the epidemiology and control of ECF is discussed. PMID- 27005903 TI - Quality of diet and mortality among Japanese men and women: Japan Public Health Center based prospective study. AB - OBJECTIVE: To examine the association between adherence to the Japanese Food Guide Spinning Top and total and cause specific mortality. DESIGN: Large scale population based prospective cohort study in Japan with follow-up for a median of 15 years. SETTING: 11 public health centre areas across Japan. PARTICIPANTS: 36,624 men and 42,970 women aged 45-75 who had no history of cancer, stroke, ischaemic heart disease, or chronic liver disease. MAIN OUTCOME MEASURES: Deaths and causes of death identified with the residential registry and death certificates. RESULTS: Higher scores on the food guide (better adherence) were associated with lower total mortality; the multivariable adjusted hazard ratios (95% confidence interval) of total mortality for the lowest through highest scores were 1.00, 0.92 (0.87 to 0.97), 0.88 (0.83 to 0.93), and 0.85 (0.79 to 0.91) (P<0.001 for trend) and the multivariable adjusted hazard ratio associated with a 10 point increase in food guide scores was 0.93 (0.91 to 0.95; P<0.001 for trend). This score was inversely associated with mortality from cardiovascular disease (hazard ratio associated with a 10 point increase 0.93, 0.89 to 0.98; P=0.005 for trend) and particularly from cerebrovascular disease (0.89, 0.82 to 0.95; P=0.002 for trend). There was some evidence, though not significant, of an inverse association for cancer mortality (0.96, 0.93 to 1.00; P=0.053 for trend). CONCLUSION: Closer adherence to Japanese dietary guidelines was associated with a lower risk of total mortality and mortality from cardiovascular disease, particularly from cerebrovascular disease, in Japanese adults. PMID- 27005906 TI - Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment. AB - Olmesartan is a hydrophobic antihypertensive drug with a short biological half life, and low bioavailability, presents a challenge with respect to its oral administration. The objective of the work was to formulate, optimize and evaluate the transdermal potential of novel vesicular nano-invasomes, containing above anti-hypertensive agent. To achieve the above purpose, soft carriers (viz. nano invasomes) of olmesartan with beta-citronellene as potential permeation enhancer were developed and optimized using Box-Behnken design. The physicochemical characteristics e.g., vesicle size, shape, entrapment efficiency and skin permeability of the nano-invasomes formulations were evaluated. The optimized formulation was further evaluated for in vitro drug release, confocal microscopy and in vivo pharmacokinetic study. The optimum nano-invasomes formulation showed vesicles size of 83.35+/-3.25nm, entrapment efficiency of 65.21+/-2.25% and transdermal flux of 32.78+/-0.703 (MUg/cm(2)/h) which were found in agreement with the predicted value generated by Box-Behnken design. Confocal laser microscopy of rat skin showed that optimized formulation was eventually distributed and permeated deep into the skin. The pharmacokinetic study presented that transdermal nano-invasomes formulation showed 1.15 times improvement in bioavailability of olmesartan with respect to the control formulation in Wistar rats. It was concluded that the response surfaces estimated by Design Expert((r)) illustrated obvious relationship between formulation factors and response variables and nano-invasomes were found to be a proficient carrier system for transdermal delivery of olmesartan. PMID- 27005908 TI - Boosting materials modelling. PMID- 27005907 TI - Diagnostic 'omics' for active tuberculosis. AB - The decision to treat active tuberculosis (TB) is dependent on microbiological tests for the organism or evidence of disease compatible with TB in people with a high demographic risk of exposure. The tuberculin skin test and peripheral blood interferon-gamma release assays do not distinguish active TB from a cleared or latent infection. Microbiological culture of mycobacteria is slow. Moreover, the sensitivities of culture and microscopy for acid-fast bacilli and nucleic acid detection by PCR are often compromised by difficulty in obtaining samples from the site of disease. Consequently, we need sensitive and rapid tests for easily obtained clinical samples, which can be deployed to assess patients exposed to TB, discriminate TB from other infectious, inflammatory or autoimmune diseases, and to identify subclinical TB in HIV-1 infected patients prior to commencing antiretroviral therapy. We discuss the evaluation of peripheral blood transcriptomics, proteomics and metabolomics to develop the next generation of rapid diagnostics for active TB. We catalogue the studies published to date seeking to discriminate active TB from healthy volunteers, patients with latent infection and those with other diseases. We identify the limitations of these studies and the barriers to their adoption in clinical practice. In so doing, we aim to develop a framework to guide our approach to discovery and development of diagnostic biomarkers for active TB. PMID- 27005910 TI - Materials modelling in London. PMID- 27005909 TI - Nucleic acid memory. PMID- 27005911 TI - Mechanical metamaterials: Smaller and stronger. PMID- 27005912 TI - Organic materials: Echoes from diffusion. PMID- 27005913 TI - Material witness: From pillar to post. PMID- 27005914 TI - Chiral nanocomposites: Hand-twisting light. PMID- 27005915 TI - Wetting: Bumps lead the way. PMID- 27005916 TI - Hydrogel composites: Shaped after print. PMID- 27005917 TI - Materials modelling: The frontiers and the challenges. PMID- 27005918 TI - Metal oxides for optoelectronic applications. AB - Metal oxides (MOs) are the most abundant materials in the Earth's crust and are ingredients in traditional ceramics. MO semiconductors are strikingly different from conventional inorganic semiconductors such as silicon and III-V compounds with respect to materials design concepts, electronic structure, charge transport mechanisms, defect states, thin-film processing and optoelectronic properties, thereby enabling both conventional and completely new functions. Recently, remarkable advances in MO semiconductors for electronics have been achieved, including the discovery and characterization of new transparent conducting oxides, realization of p-type along with traditional n-type MO semiconductors for transistors, p-n junctions and complementary circuits, formulations for printing MO electronics and, most importantly, commercialization of amorphous oxide semiconductors for flat panel displays. This Review surveys the uniqueness and universality of MOs versus other unconventional electronic materials in terms of materials chemistry and physics, electronic characteristics, thin-film fabrication strategies and selected applications in thin-film transistors, solar cells, diodes and memories. PMID- 27005920 TI - Subfoveal perfluorocarbon liquid. Removal after three months. AB - CLINICAL CASE: A case of surgical removal of a subfoveal perfluorocarbon liquid (PFCL) bubble that remained trapped inside the subretinal space. PFCL bubble extraction was performed by performing a therapeutic and vacuum PFCL bubble macular retinal detachment. DISCUSSION: The elapsed time before subfoveal PFCL extraction seems to influence the visual result. There are other factors which could influence the final visual acuity significantly, nevertheless it is possible to achieve useful vision, as long as the fovea is not damaged and iatrogenic injuries are avoided during PFCL bubble extraction. PMID- 27005919 TI - Plasma Levels of Risk-Variant APOL1 Do Not Associate with Renal Disease in a Population-Based Cohort. AB - Two common missense variants in APOL1 (G1 and G2) have been definitively linked to CKD in black Americans. However, not all individuals with the renal-risk genotype develop CKD, and little is known about how APOL1 variants drive disease. Given the association of APOL1 with HDL particles, which are cleared by the kidney, differences in the level or quality of mutant APOL1-HDL particles could be causal for disease and might serve as a useful risk stratification marker. We measured plasma levels of G0 (low risk), G1, and G2 APOL1 in 3450 individuals in the Dallas Heart Study using a liquid chromatography-MS method that enabled quantitation of the different variants. Additionally, we characterized native APOL1-HDL from donors with no or two APOL1 risk alleles by size-exclusion chromatography and analysis of immunopurified APOL1-HDL particles. Finally, we identified genetic loci associated with plasma APOL1 levels and tested for APOL1 dependent association with renal function. Although we replicated the previous association between APOL1 variant status and renal function in nondiabetic individuals, levels of circulating APOL1 did not associate with microalbuminuria or GFR. Furthermore, the size or known components of APOL1-HDL did not consistently differ in subjects with the renal-risk genotype. Genetic association studies implicated variants in loci harboring haptoglobin-related protein (HPR), APOL1, and ubiquitin D (UBD) in the regulation of plasma APOL1 levels, but these variants did not associate with renal function. Collectively, these data demonstrate that the risk of renal disease associated with APOL1 is probably not related to circulating levels of the mutant protein. PMID- 27005921 TI - Signs of hydroxychloroquine toxicity in a patient with rhegmatogenous retinal detachment. AB - CLINICAL CASE: The case is presented of a 56 year-old patient diagnosed with rhegmatogenous retinal detachment and on treatment with hydroxychloroquine (HCQ). A Spectral Domain-Optical Coherence Tomography (SD-OCT) was performed that showed changes in the outer retina in the eye with macular detachment, as well as the "flying saucer" sign in the other eye. After a complete retinopexy the "flying saucer" sign was still present. DISCUSSION: SD-OCT could be used as a test in order to reveal HCQ toxicity in the event of retinal detachment. In this case, this technique shows abnormalities such as a hyper-reflective line in the outer retina layers. PMID- 27005922 TI - Identification of a novel HLA-A*02 variant, HLA-A*02:610, in a Taiwanese individual. AB - One nucleotide substitution at residue 204 of the HLA-A*02:01:01:01 results in a new allele, HLA-A*02:610. PMID- 27005924 TI - CP91 is a component of the Dictyostelium centrosome involved in centrosome biogenesis. AB - The Dictyostelium centrosome is a model for acentriolar centrosomes and it consists of a three-layered core structure surrounded by a corona harboring microtubule nucleation complexes. Its core structure duplicates once per cell cycle at the G2/M transition. Through proteomic analysis of isolated centrosomes we have identified CP91, a 91-kDa coiled coil protein that was localized at the centrosomal core structure. While GFP-CP91 showed almost no mobility in FRAP experiments during interphase, both GFP-CP91 and endogenous CP91 dissociated during mitosis and were absent from spindle poles from late prophase to anaphase. Since this behavior correlates with the disappearance of the central layer upon centrosome duplication, CP91 is a putative component of this layer. When expressed as GFP-fusions, CP91 fragments corresponding to the central coiled coil domain and the preceding N-terminal part (GFP-CP91cc and GFP-CP91N, respectively) also localized to the centrosome but did not show the mitotic redistribution of the full length protein suggesting a regulatory role of the C-terminal domain. Expression of all GFP-fusion proteins suppressed expression of endogenous CP91 and elicited supernumerary centrosomes. This was also very prominent upon depletion of CP91 by RNAi. Additionally, CP91-RNAi cells exhibited heavily increased ploidy due to severe defects in chromosome segregation along with increased cell size and defects in the abscission process during cytokinesis. Our results indicate that CP91 is a central centrosomal core component required for centrosomal integrity, proper centrosome biogenesis and, independently, for abscission during cytokinesis. PMID- 27005923 TI - Evaluation of the significance of cell wall polymers in flax infected with a pathogenic strain of Fusarium oxysporum. AB - BACKGROUND: Fusarium oxysporum infection leads to Fusarium-derived wilt, which is responsible for the greatest losses in flax (Linum usitatissimum) crop yield. Plants infected by Fusarium oxysporum show severe symptoms of dehydration due to the growth of the fungus in vascular tissues. As the disease develops, vascular browning and leaf yellowing can be observed. In the case of more virulent strains, plants die. The pathogen's attack starts with secretion of enzymes degrading the host cell wall. The main aim of the study was to evaluate the role of the cell wall polymers in the flax plant response to the infection in order to better understand the process of resistance and develop new ways to protect plants against infection. For this purpose, the expression of genes involved in cell wall polymer metabolism and corresponding polymer levels were investigated in flax seedlings after incubation with Fusarium oxysporum. RESULTS: This analysis was facilitated by selecting two groups of genes responding differently to the infection. The first group comprised genes strongly affected by the infection and activated later (phenylalanine ammonia lyase and glucosyltransferase). The second group comprised genes which are slightly affected (up to five times) and their expression vary as the infection progresses. Fusarium oxysporum infection did not affect the contents of cell wall polymers, but changed their structure. CONCLUSION: The results suggest that the role of the cell wall polymers in the plant response to Fusarium oxysporum infection is manifested through changes in expression of their genes and rearrangement of the cell wall polymers. Our studies provided new information about the role of cellulose and hemicelluloses in the infection process, the change of their structure and the expression of genes participating in their metabolism during the pathogen infection. We also confirmed the role of pectin and lignin in this process, indicating the major changes at the mRNA level of lignin metabolism genes and the loosening of the pectin structure. PMID- 27005926 TI - The impact of vessel speed reduction on port accidents. AB - Reduced-speed zones (RSZs) have been designated across the world to control emissions from ships and prevent mammal strikes. While some studies have examined the effectiveness of speed reduction on emissions and mammal preservation, few have analyzed the effects of reduced ship speed on vessel safety. Those few studies have not yet measured the relationship between vessel speed and accidents by using real accident data. To fill this gap in the literature, this study estimates the impact of vessel speed reduction on vessel damages, casualties and frequency of vessel accidents. Accidents in RSZ ports were compared to non-RSZ ports by using U.S. Coast Guard data to capture the speed reduction effects. The results show that speed reduction influenced accident frequency as a result of two factors, the fuel price and the RSZ designation. Every $10 increase in the fuel price led to a 10.3% decrease in the number of accidents, and the RSZ designation reduced vessel accidents by 47.9%. However, the results do not clarify the exact impact of speed reduction on accident casualty. PMID- 27005925 TI - Urinary carbonic anhydrase IX splicing messenger RNA variants in urogenital cancers. AB - BACKGROUND: To identify molecular biomarkers for tumor diagnosis and monitoring of disease progression, several noninvasive tests on liquid biopsy have been proposed for different cancers including those of urogenital origin. Among biomarkers, carbonic anhydrase IX (CAIX) has gained attention as it regulates extracellular pH and induces cytoplasmic alkalization contributing to malignant progression and poor treatment outcome. Works on tissues suggested the potential use of CAIX as a tumor biomarker for urogenital malignancies, but only few studies have been performed on its detection in urine. SCOPE: The aim of the present study is the measurement of CAIX messenger RNA (mRNA) in urine sediments of patients affected by kidney, prostate, and bladder cancers to evaluate the clinical sensitivity and specificity of the test. PROCEDURES: The quantification of the total CAIX mRNA concentration and of its full-length isoform (CAIX FL) have been performed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on RNA extracted from urine sediments of patients affected by urogenital cancers. RESULTS: Urinary total CAIX mRNA expression resulted to be lower in patients with kidney and prostate cancer in comparison with the control group, but no statistically significant difference could be evidenced for bladder cancer. The evaluation of the relative percentage of FL isoform mRNA (FL%) showed a significant increase of FL% in urine from patients with cancer (median = 70.8%) in comparison with the healthy subjects (median = 2.6%) and this finding was confirmed for each cancer type separately. The comparison among receiver operating characteristic curves for total CAIX mRNA, CAIX FL mRNA, and FL% indicated that FL% shows the best diagnostic performance with 90% sensitivity and 72% specificity. Comparison of the results obtained in urine with those found in the corresponding tissues indicated 80% concordance. CONCLUSIONS: The CAIX mRNA expression in urine sediments can be considered a surrogate marker of CAIX expression in tumor tissues of urogenital origin. In particular, the analysis of FL% possesses the best characteristics to be a suitable noninvasive biomarker for urogenital cancer diagnosis. PMID- 27005927 TI - Efficacy, safety, and acceptability of thermocoagulation for treatment of cervical intraepithelial neoplasia in a hospital setting in Brazil. AB - OBJECTIVE: To analyze the acceptability, safety, and effectiveness of thermocoagulation for the treatment of histologically proven cervical intraepithelial neoplasia grade 2-3 (CIN2-3) lesions. METHODS: In a retrospective study, data were obtained for women treated for CIN2-3 lesions by thermocoagulation at the Hospital de Clinicas de Porto Alegre, Brazil, between March 6, 2012, and October 29, 2013, and followed up after 1 year. The proportions of women with no evidence of disease, adverse effects, or complications were determined. RESULTS: Among 52 women included, 44 (85%) had no evidence of disease 1year after thermocoagulation. The rate of no disease at follow-up was similar for women treated for CIN2 (17/20 [85%]) and CIN3 (27/32 [84%]). No serious adverse effects or complications requiring hospitalization were observed during the follow-up period. CONCLUSION: Thermocoagulation is useful in the management of ectocervical CIN and should be integrated into public health services for management of cervical cancer. PMID- 27005928 TI - [Atypical morphological feature of a cerebellar tumor]. PMID- 27005929 TI - Postmortem genetic analysis of sudden unexplained death syndrome under 50 years of age: A next-generation sequencing study. AB - BACKGROUND: Recent studies on the genetic analysis of victims of sudden unexplained death syndrome (SUDS) have shown diagnostic potential. Previously, such analyses mainly targeted the major channelopathy-associated genes. OBJECTIVE: The purpose of this study was to evaluate the utility of next generation sequencing (NGS) in the postmortem diagnosis of SUDS. METHODS: Our data are derived from 25 cases of SUDS (21 men and 4 women; age 19-50 years). A total of 70 genes were examined by NGS, and the pathogenicity of any detected rare variants with minor allele frequencies of <0.5% was evaluated using a widely used database and eight in silico algorithms. RESULTS: Five known and 15 potentially pathogenic variants with a high in silico score were identified in 14 cases. In all, 6 channelopathy-related variants were identified in 5 cases, including 2 cases with history of arrhythmia; 11 cases had cardiomyopathy- or cardiac transcription factor-related variants. Three cases with desmosomal gene- or other cardiomyopathy-related variants showed possibly related pathologic changes. Three cases with RYR2 or TBX5 variants showed possible pathogenic fibrosis of the cardiac conduction system. Only 12 variants showed moderate or strong possible pathogenicity in SUDS cases compared with qualifying controls. CONCLUSION: Hereditary heart diseases other than channelopathy may also be a significant cause of SUDS, even if clinical and pathologic findings do not show advanced disease. A combination of gene analysis using NGS and some predictive methods for detecting variants and careful pathologic evaluation may provide a reliable diagnosis of hereditary heart disease for potential SUDS cases. PMID- 27005930 TI - Prolonged atrial refractoriness predicts the onset of atrial fibrillation: A 12 year follow-up study. AB - BACKGROUND: Tissue refractoriness to conduction is a crucial electrophysiological factor in determining susceptibility to fibrillation. The relationship between atrial refractoriness and future onset of atrial fibrillation (AF) has not been well studied. OBJECTIVES: We investigated whether atrial effective refractory period (AERP) was associated with AF occurrence in a relatively healthy population. METHODS: A total of 1308 patients with no overt structural heart diseases and no evidence of congestive heart failure who underwent electrophysiology studies for paroxysmal supraventricular tachycardia from January 1986 to January 2011 were included in the study (626 male, mean age 44 +/ 16 years). RESULTS: AERP increased with increasing age. Over a mean follow-up of 12 years, 51 of 1308 subjects (3.9%) developed AF. In univariate analysis, baseline AERP >=280 ms (hazard ratio [HR] 2.54, 95% confidence interval [CI] 1.27 5.07, P = .008) was strongly associated with new-onset AF. In multivariate Cox regression analysis, age (adjusted HR 1.40 per 10 years, 95% CI 1.15-1.70, P = .001) and AERP >=280 ms (adjusted HR 2.08, 95% CI 1.03-4.21, P = .041) were associated with new-onset AF. Kaplan-Meier AF-free survival curves demonstrated that subjects with an AERP of >=280 ms had significantly lower AF-free survival compared those with AERP of <280 ms. CONCLUSIONS: AERP increases with age and AERP of >=280 ms was predictive of patients at significantly increased future risk of developing AF. PMID- 27005931 TI - Transthoracic Computed Tomography-Guided Lung Nodule Biopsy: Comparison of Core Needle and Fine Needle Aspiration Techniques. AB - PURPOSE: To determine if there is a statistically significant difference in the computed tomography (CT)-guided trans-thoracic needle biopsy diagnostic rate, complication rate, and degree of pathologist confidence in diagnosis between core needle biopsy (CNB) and fine needle aspiration biopsy (FNAB). METHODS: A retrospective cohort design was used to compare the diagnostic biopsy rate, diagnostic confidence, and biopsy-related complications of pneumothorax, chest tube placement, pulmonary hemorrhage, hemoptysis, admission to hospital, and length of stay between 251 transthoracic needle biopsies obtained via CNB (126) or FNAB (125). Complication rates were assessed using imaging and clinical follow up. Final diagnosis was confirmed via surgical pathology or clinical follow-up over a period of up to 10 years. RESULTS: CNB provided diagnostic samples in 91% and FNA in 80% of biopsies, which was statistically significant (P < .05). The sensitivities for CNB and FNAB were 89% (85 of 95) and 95% (84 of 88), respectively. The specificity of CNB was 100% (21 of 21) and for FNAB was 81% (2 of 11) with 2 false positives in the FNAB group. The differences in complication rate was not statistically significant for pneumothorax (50% vs 46%; determined by routine postbiopsy CT), chest tube (2% vs 4%), hemoptysis (4% vs 6%), and pulmonary hemorrhage (38% vs 47%) between FNAB and CNB, respectively. Seven patients requiring chest tube were admitted to hospital, 2 in the FNAB cohort for an average of 2.5 days and 5 in the CNB cohort for an average of 4.6 days. CONCLUSIONS: CNB provided more diagnostic samples with no statistical difference in complication rate. PMID- 27005932 TI - Sex differences between Veterans participating in interdisciplinary chronic pain rehabilitation. AB - The improved management of pain among the growing number of female Veterans receiving care through the Veterans Health Administration has been established as a priority, but studies suggest that females may respond differently to pain treatment. This study explored differences between female and male Veterans engaged in a Chronic Pain Rehabilitation Program and determined how female and male Veterans change following participation. Veterans (N = 324) in a 3 wk inpatient program completed self-report measures at admission, discharge, and 3 mo follow-up. Participants were 21% female (n = 67) and 79% male (n = 257). Compared with males, females were younger and less likely to be white or married/partnered. Females reported shorter pain duration and were more likely to have primary head or limb pain. At admission, fewer females were prescribed opioids than males and at lower doses. After opioid cessation in the program, however, there were no significant differences in use between the sexes at follow up. Improvements in a range of domains were sustained at follow-up for both sexes, but females did not maintain gains in pain intensity or sleep while males reported more pain-related fear at discharge and follow-up. This study adds to the literature on sex-specific variations in chronic pain and implications for treatment. PMID- 27005933 TI - Selenium Deficiency Activates Heat Shock Protein Expression in Chicken Spleen and Thymus. AB - Heat shock proteins (Hsps) are protective proteins present in nearly all species; they are used as biomarkers of various stress conditions in humans, animals, and birds. Selenium (Se) deficiency, which can depress the production of Hsps, can cause chicken tissue injuries. To investigate Hsp production, mRNA, and protein levels in Se-deficient chicken spleens and thymuses, a total of 180 1-day-old sea blue white laying hens (90 chickens/group) were harvested in two groups (the control group and the Se-deficient group) in 15, 25, 35, 45, and 55 days, respectively. The results showed that mRNA levels of Hsp27, Hsp40, Hsp60, Hsp70, and Hsp90 were significantly increased in the spleens and thymuses of the Se deficient group compared to the control group. Further protein levels of Hsp60, Hsp70, and Hsp90 were also significantly increased in the spleen and thymus of the Se-deficient group compared to the control group. Meanwhile, the spleen expression ratio of Hsp40 mRNA level and Hsp70 protein level were higher in the Se-deficient group than other proteins. In the thymus, the Hsp90 mRNA level and Hsp60 protein expression level were the highest level in the Se-deficient group among other proteins. Based on these results, we concluded that Se deficiency could induce a protective stress response in chicken by means of promoting the mRNA and protein expression of Hsps, thus easing the effects of Se deficiency to some extent. PMID- 27005934 TI - caOmicsV: an R package for visualizing multidimensional cancer genomic data. AB - BACKGROUND: Translational genomics research in cancers, e.g., International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), has generated large multidimensional datasets from high-throughput technologies. Data analysis at multidimensional level will greatly benefit clinical applications of genomic information in diagnosis, prognosis and therapeutics of cancers. To help, tools to effectively visualize integrated multidimensional data are important for understanding and describing the relationship between genomic variations and cancers. RESULTS: We implemented the R package, caOmicsV, to provide methods under R environment to visualize multidimensional cancer genomic data in two layouts: matrix layout and combined biological network and circular layout. Both layouts support to display sample information, gene expression (e.g., RNA and miRNA), DNA methylation, DNA copy number variations, and summarized data. A set of supplemental functions are included in the caOmicsV package to help users in generation of plot data sets from multiple genomic datasets with given gene names and sample names. Default plot methods for both layouts for easy use are also implemented. CONCLUSION: caOmicsV package provides an easy and flexible way to visualize integrated multidimensional cancer genomic data under R environment. PMID- 27005935 TI - Is late-onset disease or the lower rate of M694V mutations associated with the mild disease phenotype? PMID- 27005936 TI - Relaxin deficiency results in increased expression of angiogenesis- and remodelling-related genes in the uterus of early pregnant mice but does not affect endometrial angiogenesis prior to implantation. AB - BACKGROUND: Extensive uterine adaptations, including angiogenesis, occur prior to implantation in early pregnancy and are potentially regulated by the peptide hormone relaxin. This was investigated in two studies. First, we took a microarray approach using human endometrial stromal (HES) cells treated with relaxin in vitro to screen for target genes. Then we aimed to investigate whether or not relaxin deficiency in mice affected uterine expression of representative genes associated with angiogenesis and uterine remodeling, and also blood vessel proliferation in the pre-implantation mouse endometrium. METHODS: Normal HES cells were isolated and treated with recombinant human relaxin (10 ng/ml) for 24 h before microarray analysis. Reverse transcriptase PCR was used to analyze gene expression of relaxin and its receptor (Rxfp1) in ovaries and uteri; quantitative PCR was used to analyze steroid receptor, angiogenesis and extracellular matrix remodeling genes in the uteri of wild type (Rln+/+) and Rln-/- mice on days 1-4 of pregnancy. Immunohistochemistry localized endometrial endothelial cell proliferation and mass spectrometry measured steroid hormones in the plasma. RESULTS: Microarray analysis identified 63 well-characterized genes that were differentially regulated in HES cells after relaxin treatment. Expression of some of these genes was increased in the uterus of Rln+/+ mice by day 4 of pregnancy. There was significantly higher vascular endothelial growth factor A (VegfA), estrogen receptor 1 (Esr1), progesterone receptor (Pgr), Rxfp1, egl-9 family hypoxia-inducible factor 1 (Egln1), hypoxia inducible factor 1 alpha (Hif1alpha), matrix metalloproteinase 14 (Mmp14) and ankryn repeat domain 37 (Ankrd37) in Rln /- compared to Rln+/+ mice on day 1. Progesterone receptor expression and plasma progesterone levels were higher in Rln-/- mice compared to Rln+/+ mice. However, endometrial angiogenesis was not advanced as pre-implantation endothelial cell proliferation did not differ between genotypes. CONCLUSIONS: Relaxin treatment modulates expression of a variety of angiogenesis-related genes in HES cells. However, despite accelerated uterine gene expression of steroid receptor, progesterone and angiogenesis and extracellular matrix remodeling genes in Rln-/- mice, there was no impact on angiogenesis. We conclude that although relaxin deficiency results in phenotypic changes in the pre-implantation uterus, endogenous relaxin does not play a major role in pre-implantation angiogenesis in the mouse uterus. PMID- 27005937 TI - Transcranial direct current stimulation as a memory enhancer in patients with Alzheimer's disease: a randomized, placebo-controlled trial. AB - BACKGROUND: The purpose of this study was to assess the efficacy of transcranial direct current stimulation (tDCS) on verbal memory function in patients with Alzheimer's disease. METHODS: We conducted a randomized, placebo-controlled clinical trial in which tDCS was applied in six 30-minute sessions for 10 days. tDCS was delivered to the left temporal cortex with 2-mA intensity. A total of 25 patients with Alzheimer's disease were enrolled in the study. All of the patients were diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria. Twelve patients received active stimulation, and thirteen patients received placebo stimulation. The primary outcome measure was the change in two parallel versions of the California Verbal Learning Test-Second Edition, a standardized neuropsychological memory test normalized by age and gender. The secondary outcome measures were the Mini Mental State Examination, clock-drawing test, and Trail Making Test A and B. RESULTS: Changes in the California Verbal Learning Test-Second Edition scores were not significantly different between the active and placebo stimulation groups for immediate recall (p = 0.270), delayed recall (p = 0.052), or recognition (p = 0.089). There were nonsignificant differences in score changes on the Mini Mental State Examination (p = 0.799), clock-drawing test (p = 0.378), and Trail Making Test A (p = 0.288) and B (p = 0.093). Adverse effects were not observed. CONCLUSIONS: Compared with placebo stimulation, active tDCS stimulation in this clinical trial did not significantly improve verbal memory function in Alzheimer's disease. This study differs from previous studies in terms of the stimulation protocol, trial design, and application of standardized neuropsychological memory assessment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02518412 . Registered on 10 August 2015. PMID- 27005938 TI - Vascular endothelial microparticles-incorporated microRNAs are altered in patients with diabetes mellitus. AB - BACKGROUND: Circulating microRNAs (miRs) are differentially regulated and selectively packaged into microparticles (MPs). We evaluated whether diabetes mellitus alters circulating vascular and endothelial MP-incorporated miRs expression levels. METHODS AND RESULTS: Circulating MPs were isolated from 135 patients with or without diabetes mellitus type II and characterized using flow cytometer and electron microscope. Nine miRs involved in the regulation of vascular performance-miR-126, miR-222, miR-let7d, miR-21, miR-30, miR-92a, miR 139, miR-199a and miR-26a-were quantified in circulating MPs by reverse transcription polymerase chain reaction. Among those, miR-126 and miR-26a were significantly reduced in diabetic patients compared to non-diabetic patients. Patients with low miR-26a and miR-126 levels were at higher risk for a concomitant coronary artery disease. MP-sorting experiments showed that endothelial cells were the major cell sources of MPs containing miR-126 and miR 26a, respectively. Finally, in accordance with our clinical results, in vitro experiments revealed that hyperglycemia reduces the packaging of miR-126 and miR 26a into EMPs. CONCLUSION: Diabetes mellitus significantly alters the expression of vascular endothelial miRs in circulating endothelial MPs with potential implications on vascular heath. PMID- 27005939 TI - Emergency radiological examination of the externally stabilized pelvis--there is a catch to it: lessons learned from two cases with symphyseal disruption despite initial inconspicuous computed tomography. AB - BACKGROUND: Preclinical and early clinical external pelvic stabilization using commercially available devices has become common in trauma patient care. Thus, in the emergency department an increasing number of patients will undergo radiographic evaluation of the externally stabilized pelvis to exclude injuries. While reports exist where injuries to the pelvis were elusive to radiological examination due to the pelvic immobilization we elaborate on an algorithm to remove an external pelvic stabilizing device, prevent delayed diagnosis of pelvic disruption and thus increase patient safety. CASE PRESENTATION: We report on two patients with external pelvic stabilization presenting with an inconspicuous pubic symphysis on initial pelvic computed tomography scans. The first patient was an otherwise healthy 51-year old male being run over by his own car. He received external pelvic stabilization in the emergency department. The second patient was a 36-year old male falling from a ladder. In this patient external pelvic stabilization was performed at the scene. In the first patient no pelvic injury was obvious on computed tomography. In the second patient pelvic fractures were diagnosed, yet the presentation of the pubic symphysis appeared normal. Nevertheless, complete symphyseal disruption was diagnosed in both of them upon removal of the external pelvic stabilization and consequently required internal fixation. CONCLUSION: Based on our experience we propose an algorithm to "clear the initially immobilized pelvis" in an effort to minimize the risk of missing a serious pelvic injury and increase patient safety. This is of significant importance to orthopedic trauma surgeons and emergency physicians taking care of injured patients. PMID- 27005940 TI - A1 adenosine receptor-induced phosphorylation and modulation of transglutaminase 2 activity in H9c2 cells: A role in cell survival. AB - The regulation of tissue transglutaminase (TG2) activity by the GPCR family is poorly understood. In this study, we investigated the modulation of TG2 activity by the A1 adenosine receptor in cardiomyocyte-like H9c2 cells. H9c2 cells were lysed following stimulation with the A1 adenosine receptor agonist N(6) cyclopentyladenosine (CPA). Transglutaminase activity was determined using an amine incorporating and a protein cross linking assay. TG2 phosphorylation was assessed via immunoprecipitation and Western blotting. The role of TG2 in A1 adenosine receptor-induced cytoprotection was investigated by monitoring hypoxia induced cell death. CPA induced time and concentration-dependent increases in amine incorporating and protein crosslinking activity of TG2. CPA-induced increases in TG2 activity were attenuated by the TG2 inhibitors Z-DON and R283. Responses to CPA were blocked by PKC (Ro 31-8220), MEK1/2 (PD 98059), p38 MAPK (SB 203580) and JNK1/2 (SP 600125) inhibitors and by removal of extracellular Ca(2+). CPA triggered robust increases in the levels of TG2-associated phosphoserine and phosphothreonine, which were attenuated by PKC, MEK1/2 and JNK1/2 inhibitors. Fluorescence microscopy revealed TG2-mediated biotin-X cadaverine incorporation into proteins and proteomic analysis identified known (Histone H4) and novel (Hexokinase 1) protein substrates for TG2. CPA pre treatment reversed hypoxia-induced LDH release and decreases in MTT reduction. TG2 inhibitors R283 and Z-DON attenuated A1 adenosine receptor-induced cytoprotection. TG2 activity was stimulated by the A1 adenosine receptor in H9c2 cells via a multi protein kinase dependent pathway. These results suggest a role for TG2 in A1 adenosine receptor-induced cytoprotection. PMID- 27005941 TI - Alleviation of collagen-induced arthritis by the benzoxathiole derivative BOT-4 one in mice: Implication of the Th1- and Th17-cell-mediated immune responses. AB - Autoimmune rheumatoid arthritis is characterized by chronic inflammation and hyperplasia in the synovial joints. Although the cause of rheumatoid arthritis is largely unknown, substantial evidence has supported the importance of immune cells and inflammatory cytokines in the initiation and progression of this disease. Herein, we demonstrated that the benzoxathiole derivative 2 cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) alleviated type II collagen-induced arthritis in a mouse model. The levels of pro inflammatory cytokines are elevated in both human patients with rheumatoid arthritis and mice with collagen-induced arthritis. BOT-4-one treatment reduced the levels of pro-inflammatory cytokines in mice and endotoxin-stimulated macrophages. BOT-4-one treatment suppressed the polarization of Th1- and Th17 cell subsets by inhibiting the expression and production of their lineage specific master transcription factors and cytokines, as well as activation of signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited mitogen-activated protein kinase and NF-kappaB signaling as well as the transcriptional activities and DNA-binding of transcription factors, including activator protein-1, cAMP response element-binding protein and NF-kappaB. Our results suggest that BOT-4-one may have therapeutic potential for the treatment of chronic inflammation associated with autoimmune rheumatoid arthritis. PMID- 27005942 TI - Effectiveness of centre-based childcare interventions in increasing child physical activity: a systematic review and meta-analysis for policymakers and practitioners. AB - CONTEXT: The review describes the effectiveness of physical activity interventions implemented in centre-based childcare services and (i) examines characteristics of interventions that may influence intervention effects; (ii) describes the effects of pragmatic interventions and non-pragmatic interventions; (iii) assesses adverse effects; and (iv) describes cost-effectiveness of interventions METHODS: Data sources were Cochrane Central Register of Controlled trials, MEDLINE, EMBASE, PsycINFO, ERIC, CINAHL, SCOPUS and SPORTDISCUS. Studies selected included randomized controlled trials conducted in centre-based childcare including an intervention to increase objectively measured physical activity in children aged less than 6 years. Data were converted into standardized mean difference (SMD) and analysed using a random effects model. RESULTS: Overall interventions significantly improved child physical activity (SMD 0.44; 95% confidence interval [CI]: 0.12-0.76). Significant effects were found for interventions that included structured activity (SMD 0.53; 95% CI: 0.12 0.94), delivery by experts (SMD 1.26; 95% CI: 0.20-2.32) and used theory (SMD 0.76; 95% CI: 0.08-1.44). Non-pragmatic (SMD 0.80; 95% CI: 0.12-1.48) but not pragmatic interventions (SMD 0.10; 95% CI:-0.13-0.33) improved child physical activity. One trial reported adverse events, and no trials reported cost data. CONCLUSIONS: Intervention effectiveness varied according to intervention and trial design characteristics. Pragmatic trials were not effective, and information on cost and adverse effects was lacking. Evidence gaps remain for policymakers and practitioners regarding the effectiveness and feasibility of childcare-based physical activity interventions. PMID- 27005944 TI - Distinguishing between weedy Amaranthus species based on intron 1 sequences from the 5-enolpyruvylshikimate-3-phosphate synthase gene. AB - BACKGROUND: Hybridization between Amaranthus species and the potential for herbicide resistance to be transferred by hybridization are of growing concern in the weed science community. Early detection of evolved herbicide resistance and hybrids expressing resistance to single or multiple herbicides is important to develop an effective control strategy. RESULTS: A PCR test was developed for quick identification of weedy amaranths and any hybrids. The sequences of intron 1 for the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19) gene were determined for Amaranthus palmeri, A. spinosus, A. retroflexus, A. blitoides, A. viridis, A. tuberculatus and A. hybridus. These sequences were aligned and primers were developed in areas where the sequence differed between species. Species-specific primers and cycle conditions were successfully developed. These primers produce a single robust band only for the species for which they were designed. CONCLUSION: The PCR techniques described here allow identification of a weedy amaranth or suspect hybrid in a few hours. Using a similar target, it may be possible to design simple PCR tests to identify even more difficult to distinguish weed species or weeds prone to interspecific hybridization. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27005943 TI - Role of indoleamine 2,3-dioxygenase in an inflammatory model of murine gingiva. AB - BACKGROUND AND OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) is one of the major pathways for metabolism of tryptophan in a variety of cells, including immune cells. Increasing evidence indicates that IDO is a critical player in establishing the balance between immunity and tolerance and ultimately in the maintenance of homeostasis. By inducing inflammation in gingival tissue, we tested the hypothesis that IDO is a pivotal player in regulating the immune and inflammatory responses of gingiva. MATERIAL AND METHODS: We utilized the IDO knockout mouse model in conjunction with lipopolysaccharide (LPS)-induced inflammation. Accordingly, wild-type and IDO knockout mice were injected with LPS or vehicle in the anterior mandibular gingiva, twice over a 2-wk period, which was followed by procurement of gingival tissue for histopathology and preparation of tissue for flow cytometry-based studies. RESULTS: Clinical and histological examinations revealed a marked adverse impact of IDO deficiency on gingival inflammation. These observations were consistent with a more marked increase in the number of cells positive for the proinflammatory cytokine interleukin (IL) 17, but no significant change in the number of cells positive for the anti inflammatory cytokine IL-10, in LPS-treated IDO knockout mice. Consistent with the more marked proinflammatory impact of IDO deficiency, the percentage of regulatory T cells was much reduced in gingival tissue of LPS-treated IDO knockout mice than in gingival tissue of wild-type mice. These proinflammatory changes were accompanied with a prominent increase in apoptotic and necrotic cell death in gingival tissue of IDO knockout mice compared with wild-type mice. CONCLUSION: Collectively, our findings support a major role for IDO in the development of gingival inflammation, as an example of an inflammatory condition, and lay the foundation for subsequent studies to explore it as a novel immunotherapy target. PMID- 27005945 TI - Complex regional pain syndrome in children: incidence and clinical characteristics. AB - OBJECTIVE: To study the clinical and epidemiological characteristics of complex regional pain syndrome (CRPS) in children. PATIENTS AND METHODS: All children and adolescents under 16 years of age with a new diagnosis of CRPS who were reported to the Scottish Paediatric Surveillance Unit were included. Patients' recruitment ran between 1 November 2011 and 31 October 2015. Information was collected on patients' demography, clinical features, investigations, management and impact of disease on child and family. The diagnosis of CRPS was made on fulfilling the clinical criteria of the International Association for the Study of Pain. RESULTS: 26 cases of CRPS were reported over 4 years, giving a minimum estimated incidence of 1.16/100 000 (95% CI 0.87 to 1.44/100 000) children 5-15 years of age. Nineteen patients were female (73%) and mean age at diagnosis was 11.9 (range 5.5-15.4 years). The median interval between onset of symptoms and diagnosis was 2 months (range 1-12). The majority of children have single site involvement, with legs been more often affected than arms and the right side is more often affected than the left. There was a clear trauma at onset of the illness in 19 children and possible nerve injury in one. All investigations were normal and several treatment modalities were used with variable success. The disease had significant impacts on the patients' education and family lives. CONCLUSIONS: The estimated incidence of CRPS is 1.2/100 000 children 5-15 years old. The diagnosis of CRPS is often delayed. CRPS has a significant impact on children and their families. PMID- 27005946 TI - The Peripheral Blood Eosinophil Proteome. AB - A system-wide understanding of biological processes requires a comprehensive knowledge of the proteins in the biological system. The eosinophil is a type of granulocytic leukocyte specified early in hematopoietic differentiation that participates in barrier defense, innate immunity, and allergic disease. The proteome of the eosinophil is largely unannotated with under 500 proteins identified. We now report a map of the nonstimulated peripheral blood eosinophil proteome assembled using two-dimensional liquid chromatography coupled with high resolution mass spectrometry. Our analysis yielded 100,892 unique peptides mapping to 7,086 protein groups representing 6,813 genes as well as 4,802 site specific phosphorylation events. We account for the contribution of platelets that routinely contaminate purified eosinophils and report the variability in the eosinophil proteome among five individuals and proteomic changes accompanying acute activation of eosinophils by interleukin-5. Our deep coverage and quantitative analyses fill an important gap in the existing maps of the human proteome and will enable the strategic use of proteomics to study eosinophils in human diseases. PMID- 27005947 TI - Early Detection of Left Atrial Energy Loss and Mechanics Abnormalities in Diabetic Patients with Normal Left Atrial Size: A Study Combining Vector Flow Mapping and Tissue Tracking Echocardiography. AB - BACKGROUND: Whether left atrial (LA) functional abnormalities already exist when the LA is of normal size is unknown. The aim of this study was to explore LA energy loss and mechanics changes using vector flow mapping (VFM) and two dimensional tissue tracking (2DTT) echocardiography in patients with diabetes and normal LA size. MATERIAL/METHODS: This study included 47 normotensive patients with diabetes and 45 controls. The following indexes were measured: LA energy loss during systole (LAELs), early diastole (LAELed), and atrial contraction (LAELac); atrial longitudinal strain during systole (SLAs), early diastole (SLAed) and late diastole (SLAac); and peak LA strain rate during systole (SRLAs), early diastole (SRLAed), and atrial contraction (SRLAac). RESULTS: The LAELs and LAELed decreased in diabetic patients compared with controls (P=0.002, P<0.01, respectively), whereas the LAELac increased in diabetic patients (P<0.001). The SLAs, SLAed, SRLAs, and SRLAed (all P<0.01) were all lower in diabetic patients than in controls. However, there was no difference in the SLAac and SRLAac between the two groups. Multivariate regression analysis showed that the LAELs, LAELac, and SRLAs were independently associated with HbA(1c) in the whole study population. CONCLUSIONS: LA energy loss and deformation mechanics are already impaired in diabetic patients with normal LA size and the long-term parameter of glycemic control was correlated with them. VFM combined with 2DTT might be a promising tool for the early detection of LA dysfunction caused by impaired glucose metabolism. PMID- 27005948 TI - Solution structure of TbTFIIS2-1 PWWP domain from Trypanosoma brucei. AB - TbTFIIS2-1, one of the two TFIIS homologues of Trypanosome brucei (T. brucei), cooperates with TbTFIIS1 in regulating transcription in T. brcuei. Structurally divergent from other TFIIS homologues from higher organisms, TbTFIIS2-1 contains an additional N-terminal PWWP domain besides other three conserved domains, which may imply potential role of TbTFIIS2-1 in transcription regulation. Here, we determined the solution structure of PWWP domain of TbTFIIS2-1 by NMR spectroscopy, which was the first solution structure of PWWP domain solved in trypanosomatid. In spite of poor sequence similarity between PWWP domains, this domain of TbTFIIS2-1 adopts a conserved 3D-structure, which contains a five stranded beta-barrel and a C-terminal alpha-helix. Furthermore, we found that TbTFIIS2-1 PWWP domain may be a protein-protein interaction module without the ability of DNA recognition and methyl-group interaction. Proteins 2016; 84:912 919. (c) 2016 Wiley Periodicals, Inc. PMID- 27005949 TI - Tilt aftereffect following adaptation to translational Glass patterns. AB - Glass patterns (GPs) consist of randomly distributed dot pairs (dipoles) whose orientations are determined by specific geometric transforms. We assessed whether adaptation to stationary oriented translational GPs suppresses the activity of orientation selective detectors producing a tilt aftereffect (TAE). The results showed that adaptation to GPs produces a TAE similar to that reported in previous studies, though reduced in amplitude. This suggests the involvement of orientation selective mechanisms. We also measured the interocular transfer (IOT) of the GP-induced TAE and found an almost complete IOT, indicating the involvement of orientation selective and binocularly driven units. In additional experiments, we assessed the role of attention in TAE from GPs. The results showed that distraction during adaptation similarly modulates the TAE after adapting to both GPs and gratings. Moreover, in the case of GPs, distraction is likely to interfere with the adaptation process rather than with the spatial summation of local dipoles. We conclude that TAE from GPs possibly relies on visual processing levels in which the global orientation of GPs has been encoded by neurons that are mostly binocularly driven, orientation selective and whose adaptation-related neural activity is strongly modulated by attention. PMID- 27005950 TI - Ingestion of Bt corn pollen containing Cry1Ab/2Aj or Cry1Ac does not harm Propylea japonica larvae. AB - Propylea japonica (Thunberg) (Coleoptera: Coccinellidae) is a prevalent pollen consumer in corn fields and is therefore exposed to insecticidal proteins contained in the pollen of insect-resistant transgenic corn cultivars expressing Cry proteins derived from Bacillus thuringiensis (Bt). In the present study, the potential effect of Cry1Ab/2Aj- or Cry1Ac-containing transgenic Bt corn pollen on the fitness of P. japonica larvae was evaluated. The results show that the larval developmental time was significantly shorter when P. japonica larvae were fed pollen from Bt corn cultivars rather than control pollen but that pupation rate, eclosion rate, and adult fresh weight were not significantly affected. In the feeding experiments, the stability of the Cry proteins in the food sources was confirmed. When Bt corn pollen passed through the gut of P. japonica, 23% of Cry1Ab/2Aj was digested. The results demonstrate that consumption of Bt corn pollen containing Cry1Ab/2Aj or Cry1Ac has no detrimental effect on P. japonica larvae; the shortened developmental time of larvae that consumed these proteins was likely attributable to unknown differences in the nutritional composition between the Bt-transgenic and control corn pollen. PMID- 27005952 TI - Ethical dimensions of paediatric nursing: A rapid evidence assessment. AB - BACKGROUND: Paediatric nurses often face complex situations requiring decisions that sometimes clash with their own values and beliefs, or with the needs of the children they care for and their families. Paediatric nurses often use new technology that changes the way they provide care, but also reduces their direct interaction with the child. This may generate ethical issues, which nurses should be able to address in the full respect of the child. Research question and objectives: The purpose of this review is to describe the main ethical dimensions of paediatric nursing. Our research question was, 'What are the most common ethical dimensions and competences related to paediatric nursing?' RESEARCH DESIGN: A rapid evidence assessment. METHOD: According to the principles of the rapid evidence assessment, we searched the PubMed, SCOPUS and CINAHL databases for papers published between January 2001 and March 2015. These papers were then independently read by two researchers and analysed according to the inclusion criteria. Ethical considerations: Since this was a rapid evidence assessment, no approval from the ethics committee was required. FINDINGS: Ten papers met our inclusion criteria. Ethical issues in paediatric nursing were grouped into three areas: (a) ethical issues in paediatric care, (b) social responsibility and (c) decision-making process. CONCLUSION: Few studies investigate the ethical dimensions and aspects of paediatric nursing, and they are mainly qualitative studies conducted in critical care settings based on nurses' perceptions and experiences. Paediatric nurses require specific educational interventions to help them resolve ethical issues, contribute to the decision-making process and fulfil their role as advocates of a vulnerable population (i.e. sick children and their families). Further research is needed to investigate how paediatric nurses can improve the involvement of children and their families in decision-making processes related to their care plan. PMID- 27005953 TI - Moral courage in nursing: A concept analysis. AB - BACKGROUND: Nursing as an ethical practice requires courage to be moral, taking tough stands for what is right, and living by one's moral values. Nurses need moral courage in all areas and at all levels of nursing. Along with new interest in virtue ethics in healthcare, interest in moral courage as a virtue and a valued element of human morality has increased. Nevertheless, what the concept of moral courage means in nursing contexts remains ambiguous. OBJECTIVE: This article is an analysis of the concept of moral courage in nursing. DESIGN: Rodgers' evolutionary method of concept analysis provided the framework to conduct the analysis. DATA SOURCES: The literature search was carried out in September 2015 in six databases: PubMed, CINAHL, Scopus, Web of Science, PsycINFO, and The Philosopher's Index. The following key words were used: "moral" OR "ethical" AND "courage" OR "strength" AND "nurs*" with no time limit. After applying inclusion and exclusion criteria, 31 studies were included in the final analysis. Ethical considerations: This study was conducted according to good scientific guidelines. RESULTS: Seven core attributes of moral courage were identified: true presence, moral integrity, responsibility, honesty, advocacy, commitment and perseverance, and personal risk. Antecedents were ethical sensitivity, conscience, and experience. Consequences included personal and professional development and empowerment. DISCUSSION AND CONCLUSION: This preliminary clarification warrants further exploring through theoretical and philosophical literature, expert opinions, and empirical research to gain validity and reliability for its application in nursing practice. PMID- 27005951 TI - VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread. AB - The specific role of VEGFA-induced permeability and vascular leakage in physiology and pathology has remained unclear. Here we show that VEGFA-induced vascular leakage depends on signalling initiated via the VEGFR2 phosphosite Y949, regulating dynamic c-Src and VE-cadherin phosphorylation. Abolished Y949 signalling in the mouse mutant Vegfr2(Y949F/Y949F) leads to VEGFA-resistant endothelial adherens junctions and a block in molecular extravasation. Vessels in Vegfr2(Y949F/Y949F) mice remain sensitive to inflammatory cytokines, and vascular morphology, blood pressure and flow parameters are normal. Tumour-bearing Vegfr2(Y949F/Y949F) mice display reduced vascular leakage and oedema, improved response to chemotherapy and, importantly, reduced metastatic spread. The inflammatory infiltration in the tumour micro-environment is unaffected. Blocking VEGFA-induced disassembly of endothelial junctions, thereby suppressing tumour oedema and metastatic spread, may be preferable to full vascular suppression in the treatment of certain cancer forms. PMID- 27005955 TI - Immunological detection of Cronobacter and Salmonella in powdered infant formula by plasmonic label-free assay. AB - Cronobacter is an emerging food pathogen, especially in infants and neonates, often associated with the ingestion of contaminated Powdered Infant Formula (PIF). Therefore, regulations require the control of the absence of Cronobacter and of Salmonella, another important food pathogen, in these food products. So far, reference and alternative methods take up to several days, and no validated method exists for the simultaneous detection of these two pathogens. In this work, we propose to address this issue by an innovative and easy-to-operate assay, named Plasmonic Immuno-Assay (PlasmIA), and by producing dedicated polyclonal antibodies. Our approach is based on Surface Plasmon Resonance imaging of antibody-arrays and bacterial growth during a standardized enrichment. Such a single-step assay enables the multiplex detection of both Cronobacter and Salmonella, with concentrations smaller than 30 CFU cells in 25 g PIF samples, in less than 1 day. SIGNIFICANCE AND IMPACT OF THE STUDY: Among bacterial pathogens involved in food contamination, Cronobacter and Salmonella are of particular interest. Nevertheless, all detection methods used so far require several days to assess food safety. In the present paper, we describe the first multiplex immuno assay ever described for fast and specific detection of these two pathogens in food samples. Such advances were made possible by combining the advantages of protein microarrays with on-biochip culture of contaminated food samples and an easy-to-operate optical detection. By doing so, we managed to detect both viable Cronobacter and Salmonella occurring during the enrichment phase. PMID- 27005954 TI - Ethical frameworks for surrogates' end-of-life planning experiences. AB - BACKGROUND: Despite the growing body of knowledge about surrogate decision making, we know very little about the use of ethical frameworks (including ethical theories, principles, and concepts) to understand surrogates' day-to-day experiences in end-of-life care planning for incapacitated adults. OBJECTIVES AND METHODS: This qualitative systematic review was conducted to identify the types of ethical frameworks used to address surrogates' experiences in end-of-life care planning for incapacitated adults as well as the most common themes or patterns found in surrogate decision-making research. FINDINGS: Seven research papers explicitly identified ethical theories, principles, or concepts, such as autonomy, substituted judgment, and best interest standards as guidelines for the research. Surrogate decision making themes included the responsibilities and goals of being a surrogate, factors influencing surrogates' decision making, outcomes for surrogates, and an overarching theme of "wanting to do the right thing" for their loved one and/or themselves. DISCUSSION: Understanding the complexity of surrogates' experiences of end-of-life care planning is beyond the scope of conventional ethical frameworks. CONCLUSION: Ethical frameworks that address individuality and contextual variations related to decision making may more appropriately guide surrogate decision-making research that explores surrogates' end-of-life care planning experiences. PMID- 27005957 TI - What is a 'good' job? Modelling job quality for blue collar workers. AB - This paper proposes a model of job quality, developed from interviews with blue collar workers: bus drivers, manufacturing operatives and cleaners (n = 80). The model distinguishes between core features, important for almost all workers, and 'job fit' features, important to some but not others, or where individuals might have different preferences. Core job features found important for almost all interviewees included job security, personal safety and having enough pay to meet their needs. 'Job fit' features included autonomy and the opportunity to form close relationships. These showed more variation between participants; priorities were influenced by family commitments, stage of life and personal preference. The resulting theoretical perspective indicates the features necessary for a job to be considered 'good' by the person doing it, whilst not adversely affecting their health. The model should have utility as a basis for measuring and improving job quality and the laudable goal of creating 'good jobs'. Practitioner Summary: Good work can contribute positively to health and well-being, but there is a lack of agreement regarding the concept of a 'good' job. A model of job quality has been constructed based on semi-structured worker interviews (n = 80). The model emphasises the need to take into account variation between individuals in their preferred work characteristics. PMID- 27005956 TI - Preventing (impulsive) errors: Electrophysiological evidence for online inhibitory control over incorrect responses. AB - In a rich environment, with multiple action affordances, selective action inhibition is critical in preventing the execution of inappropriate responses. Here, we studied the origin and the dynamics of incorrect response inhibition and how it can be modulated by task demands. We used EEG in a conflict task where the probability of compatible and incompatible trials was varied. This allowed us to modulate the strength of the prepotent response, and hence to increase the risk of errors, while keeping the probability of the two responses equal. The correct response activation and execution was not affected by compatibility or by probability. In contrast, incorrect response inhibition in the primary motor cortex ipsilateral to the correct response was more pronounced on incompatible trials, especially in the condition where most of the trials were compatible, indicating a modulation of inhibitory strength within the course of the action. Two prefrontal activities, one medial and one lateral, were also observed before the response, and their potential links with the observed inhibitory pattern observed are discussed. PMID- 27005958 TI - Myoimaging in the NGS era: the discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features--a case report. AB - BACKGROUND: Myosin heavy chain 7 related myopathies are rare disorders characterized by a wide phenotypic spectrum and heterogeneous pathological features. In the present study, we performed clinical, morphological, genetic and imaging investigations in three relatives affected by autosomal dominant distal myopathy. Whilst earlier traditional Sanger investigations had pointed to the wrong gene as disease causative, next-generation sequencing allowed us to obtain the definitive molecular genetic diagnosis in the family. CASE PRESENTATION: The proposita, being found to harbor a novel heterozygous mutation in the RYR1 gene (p.Glu294Lys), was initially diagnosed with core myopathy. Subsequently, consideration of muscle magnetic resonance imaging (MRI) features and extension of family study led this diagnosis to be questioned. Use of next-generation sequencing analysis identified a novel mutation in the MYH7gene (p.Ser1435Pro) that segregated in the affected family members. CONCLUSIONS: This study identified a novel mutation in MYH7 in a family where the conclusive molecular diagnosis was reached through a complicated path. This case report might raise awareness, among clinicians, of the need to interpret NGS data in combination with muscle MRI patterns so as to facilitate the pinpointing of the main molecular etiology in inherited muscle disorders. PMID- 27005959 TI - Dimethyloxalylglycine may be enhance the capacity of neural-like cells in treatment of Alzheimer disease. AB - Although using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats. PMID- 27005961 TI - Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention. AB - SCOPE: People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n-3 PUFAs have been observed. We aimed to assess the impact of APOE genotype on peripheral blood mononuclear cell whole genome gene expression at baseline and following a fish-oil intervention. METHODS AND RESULTS: Participants received 6 months of fish-oil supplementation containing 1800 mg of eicosapentaenoic acid and docosahexaenoic acid per day. APOE genotype and peripheral blood mononuclear cell whole genome gene expression before and after supplementation were measured. We characterized the differences in gene expression profiles in carriers of APOE4 (N = 8) compared to noncarriers (N = 15). At baseline, 1320 genes were differentially expressed and the fish-oil supplementation differentially regulated 866 genes between APOE4 carriers and noncarriers. Gene set enrichment analysis showed that carriers had a higher gene expression of cholesterol biosynthesis and IFN signaling pathways. Fish-oil supplementation reduced expression of IFN-related genes in carriers only. CONCLUSION: The increased expression of IFN signaling and cholesterol biosynthesis pathways might explain part of the association between APOE4 and CVD. Fish-oil supplementation may particularly benefit APOE4 carriers by decreasing expression of IFN-related genes. PMID- 27005960 TI - ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation. AB - The lipid mediator lysophosphatidic acid (LPA) signals via six distinct G protein coupled receptors to mediate both unique and overlapping biological effects, including cell migration, proliferation and survival. LPA is produced extracellularly by autotaxin (ATX), a secreted lysophospholipase D, from lysophosphatidylcholine. ATX-LPA receptor signaling is essential for normal development and implicated in various (patho)physiological processes, but underlying mechanisms remain incompletely understood. Through gene targeting approaches in zebrafish and mice, we show here that loss of ATX-LPA1 signaling leads to disorganization of chondrocytes, causing severe defects in cartilage formation. Mechanistically, ATX-LPA1 signaling acts by promoting S-phase entry and cell proliferation of chondrocytes both in vitro and in vivo, at least in part through beta1-integrin translocation leading to fibronectin assembly and further extracellular matrix deposition; this in turn promotes chondrocyte-matrix adhesion and cell proliferation. Thus, the ATX-LPA1 axis is a key regulator of cartilage formation. PMID- 27005963 TI - Modelling flavoenzymatic charge transfer events: development of catalytic indole deuteration strategies. AB - The formation and chemistry of flavin-indole charge transfer (CT) complexes has been studied using a model cationic flavin. The ability to form a CT complex is sensitive to indole structure as gauged by spectroscopic, kinetics and crystallographic studies. Single crystals of sufficient quality of a flavin indole CT complex, suitable for X-ray diffraction, have been grown, allowing solid-state structural analysis. When CT complex formation is conducted in d4 methanol, an efficient and synthetically useful C-3 indole deuteration is observed. PMID- 27005964 TI - Establishing safe closed-system protocols in the management of hazardous drugs in oncology. PMID- 27005965 TI - An efficient solid-phase synthesis of peptidyl-N-acetylguanidines for use in native chemical ligation. AB - In the modern protocols of chemical protein syntheses, peptide-alpha-thioesters have been used as key components for the assembly of full-length polypeptides through chemoselective peptide coupling reactions. A variety of thioester precursors have been developed for the synthesis of the peptide-alpha-thioesters by Fmoc solid phase peptide synthesis (Fmoc-SPPS). Recently our group found a peptidyl-N-acetylguanidine as a new peptide-alpha-thioester precursor. This peptide derivative can be converted into a corresponding peptide-alpha-thioester only by treatment with an excess amount of a thiol in aqueous buffers at around neutral pH. This unique property allowed us to envision the practical use of the peptidyl-N-acetylguanidines for the chemical syntheses of proteins; however, an efficient synthetic method has been lacking. Herein, we report an efficient solid phase synthesis of peptidyl-N-acetylguanidines. This new synthetic method employing selective activation and cleavage of a peptide bond successfully provided peptidyl-N-acetylguanidines from the on-resin protected peptides prepared by standard Fmoc-SPPS. We also evaluated the reactivity of a peptidyl-N acetylguanidine in native chemical ligation through the synthesis of glucose dependent insulinotropic polypeptide analogue. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27005966 TI - [Use of topical nitroglycerin in newborns with ischaemic injuries after vascular cannulation]. PMID- 27005967 TI - Analyzing the Case for Bifunctional Catalysis. AB - Bifunctional coupling of two different catalytic site types has often been invoked to explain experimentally observed enhanced catalytic activities. We scrutinize such claims with generic scaling-relation-based microkinetic models that allow exploration of the theoretical limits for such a bifunctional gain for several model reactions. For sites at transition-metal surfaces, the universality of the scaling relations between adsorption energies largely prevents any improvements through bifunctionality. Only the consideration of systems that involve the combination of different materials, such as metal particles on oxide supports, offers hope for significant bifunctional gains. PMID- 27005969 TI - Molecular typing of environmental Cryptococcus neoformans/C. gattii species complex isolates from Manaus, Amazonas, Brazil. AB - Cryptococcus neoformans and Cryptococcus gattii are the main causative agents of cryptococcosis, a systemic fungal disease that affects internal organs and skin, and which is acquired by inhalation of spores or encapsulated yeasts. It is currently known that the C. neoformans/C. gattii species complex has a worldwide distribution, however, some molecular types seem to prevail in certain regions. Few environmental studies of Cryptococcus have been conducted in the Brazilian Amazon. This is the first ecological study of the pathogenic fungi C. neoformans/C. gattii species complex in the urban area of Manaus, Amazonas, Brazil. A total of 506 samples from pigeon droppings (n = 191), captive bird droppings (n = 60) and tree hollows (n = 255) were collected from June 2012 to January 2014 at schools and public buildings, squares, pet shops, households, the zoo and the bus station. Samples were plated on niger seed agar (NSA) medium supplemented with chloramphenicol and incubated at 25 degrees C for 5 days. Dark brown colonies were isolated and tested for thermotolerance at 37 degrees C, cycloheximide resistance and growth on canavanine-glycine-bromothymol blue agar. Molecular typing was done by PCR-RFLP. Susceptibility to the antifungal drugs amphotericin B, fluconazole, itraconazole and ketoconazole was tested using Etest((r)) strips. In total, 13 positive samples were obtained: one tree hollow (C. gattiiVGII), nine pigeon droppings (C. neoformansVNI) and three captive bird droppings (C. neoformansVNI). The environmental cryptococcal isolates found in this study were of the same molecular types as those responsible for infections in Manaus. PMID- 27005968 TI - Application of cancer-associated glycoforms and glycan-binding probes to an in vitro diagnostic multivariate index assay for precise diagnoses of cancer. AB - Personalized medicine has emerged as a widely accepted trend in medicine for the efficacious and safe treatment of various diseases. It covers every medical treatment tailored according to various properties of individuals. Cancer associated glycosylation mirrors cancer states more precisely, and this "sweet side of cancer" is thus intended to spur the development of an advanced in vitro diagnostic system. The changes of glyco-codes are often subtle and thus not easy to trace, thereby making it difficult to discriminate changes from various compounding factors. Special glycan-binding probes, often lectins, can be paired with aglycosylated antibodies to enable quantitative and qualitative measurements of glycoforms. With the in vitro diagnosis multivariate index assay (IVDMIA) considered to be capable of yielding patient-specific results, the combinatorial use of multiple glycoproteins may be a good modality to ensure disease-specific, personalized diagnoses. PMID- 27005970 TI - Deceleration and acceleration capacities of heart rate associated with heart failure with high discriminating performance. AB - Accurate measurements of autonomic nerve regulation in heart failure (HF) were unresolved. The discriminating performance of deceleration and acceleration capacities of heart rate in HF was evaluated in 130 HF patients and 212 controls. Acceleration capacity and deceleration capacity were independent risk factors for HF in males, evaluated by multiple logistic regression analysis, with odds ratios (ORs) of 5.94 and 0.13, respectively. Acceleration capacity was also an independent risk factor for HF in females, with an OR of 8.58. Deceleration capacity was the best cardiac electrophysiological index to classify HF in males, with an area under the receiver operating characteristic curve (AUC) of 0.88. Deceleration capacity was the best classification factor of HF in females with an AUC of 0.97, significantly higher than even left ventricular ejection fraction (LVEF). Acceleration capacity also showed high performance in classifying HF in males (0.84) and females (0.92). The cut-off values of deceleration capacity for HF classification in males and females were 4.55 ms and 4.85 ms, respectively. The cut-off values of acceleration capacity for HF classification in males and females were -6.15 ms and -5.75 ms, respectively. Our study illustrates the role of acceleration and deceleration capacity measurements in the neuro pathophysiology of HF. PMID- 27005971 TI - Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats. AB - What is the central question of this study? This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity through modulating the Nrf2 pathway by decreasing the oxidative stress. What is the main finding and its importance? Atorvastatin exerts a nephroprotective effect by attenuating oxidative stress, protecting renal function and renal organic anion transporter 3 function from the effects of gentamicin. Atorvastatin might protect the tissues via its antioxidant property and by modulating the antioxidant enzymes through the Nrf2 signalling pathway, which may be the underlying mechanisms of these protective effects. Recent evidence demonstrates that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exert not only lipid-lowering effects but also antioxidant, anti-inflammatory and anti-apoptotic effects. Nephrotoxicity, a serious side effect of gentamicin, is related to an increase in reactive oxygen species in the kidney. This study was designed to determine the renoprotective effects of atorvastatin treatment in an experimental model of gentamicin-induced nephrotoxicity. Male Sprague-Dawley rats were used. Nephrotocixity was induced by i.p. injection of gentamicin, 100 mg kg(-1) day(-1) , for 15 days. Atorvastatin, 10 mg kg(-1) day(-1) , was administered by gavage 30 min before gentamicin injection (pretreatment) for 15 days or only on days 10-15 (post-treatment). Renal function and renal organic anion transporter 3 (Oat3) function and expression were examined. Gentamicin-treated rats demonstrated impaired renal function by attenuation of creatinine clearance and increased oxidative stress. Gentamicin treatment also decreased renal Oat3 function and expression as shown by decreased [(3) H]estrone sulfate uptake into renal cortical slices and decreased expression. The protein expressions of protein kinase C, Nrf2, NAD(P)H:quinone oxidoreductase 1, haeme oxygenase 1 and glutamate-cysteine ligase were markedly increased in gentamicin-treated rats, indicating the increase in oxidative stress. Administration of atorvastatin improved renal function and alleviated oxidative stress, and atorvastatin pretreatment had a greater ability to decrease oxidative stress than atorvastatin post-treatment. These effects helped to preserve renal function and Oat3 function and expression. These results indicate that atorvastatin has a renoprotective effect against gentamicin-induced nephrotoxicity by decreasing overoxidation in the kidney, and might be used in conjunction with gentamicin to protect against renal damage. PMID- 27005972 TI - Lung cancer screening: did we really need a randomized controlled trial? AB - Lung cancer is the leading cause of cancer mortality in the USA. Within the past decade, two large trials (the National Lung Screening Trial Research and the International Early Lung Cancer Action Program) confirmed a significant role for low-dose CT (LDCT) screening in identifying early stages of cancer leading to reduced mortality in high-risk patients. Given the evidence, the US Preventive Services Task Force issued a recommendation in favour of LDCT screening for high risk individuals. Despite the strong support for LDCT among physicians who treat lung cancer and cumulative data demonstrating a survival benefit for screening and early detection, it took more than a decade for lung cancer screening to be embraced at the policy level. With many lives lost in the interim, did we really need a randomized controlled trial to make this decision? PMID- 27005973 TI - Multistage pulmonary artery rehabilitation in patients with pulmonary atresia, ventricular septal defect and hypoplastic pulmonary artery. AB - OBJECTIVES: The aim of this study was to determine the effect of multistage pulmonary artery (PA) rehabilitation consisting of right ventricle to pulmonary artery (RV-PA) connection, major aortopulmonary collateral artery (MAPCA) closure and PA angioplasty in patients with pulmonary atresia, ventricular septal defect (VSD) and hypoplastic pulmonary arteries. In addition, the effects of the PA reintervention were reported and risk factors were analysed. METHODS: This study was a retrospective review of 69 consecutive patients with pulmonary atresia, VSD and hypoplastic pulmonary arteries (mean Nakata index 100.9 +/- 57.6 mm(2)/m(2)) who underwent multistage rehabilitation of hypoplastic PA from December 2009 to December 2014. RESULTS: RV-PA connection was performed at a median age of 1.0 years with 2 hospital deaths in the hybrid operation theatre. Thirty-two patients underwent concomitant pulmonary angioplasty with 28 collateral occlusions. After a mean duration of 15.4 +/- 12.7 months, 16 patients had interventional catheterization consisting of 14 balloon dilatations, 12 stent implantations and 16 collateral occlusions. At a mean age of 2.7 +/- 1.9 years, complete repair was performed in 31 patients within 1.2 +/- 0.6 years of the palliation with 1 hospital death. Twenty-two patients had concomitant PA angioplasty. The estimated complete repair rate was 60.1 +/- 7.1% ~3 years after the palliation by the Kaplan-Meier method. During a mean follow-up of 2.8 +/- 1.3 years, 49.3% (33/67) of the patients had PA reintervention. Pulmonary stenosis requiring angioplasty at palliation is associated with PA reintervention (P = 0.003). The actuarial survival rate for the overall population was 93.8 +/- 3.0% at 5 years after the placement of an RV-PA connection. CONCLUSIONS: The multistage strategy consisting of a RV-PA connection, MAPCA closure and PA angioplasty is effective in rehabilitating the hypoplastic PA in patients with pulmonary atresia, VSD and hypoplastic pulmonary arteries. However, PA reinterventions may be required in specific patients. PMID- 27005975 TI - Giant cell aortitis: clinical presentation and outcomes in 40 patients consecutively operated on. AB - OBJECTIVES: Giant cell arteritis (GCA) may affect mid-size and large-size arteries. Although temporal arteritis is a well-characterized clinical entity, GCA of the thoracic aorta remains ill defined. The aim of the study was to evaluate the clinical presentation, surgical and mid-term outcomes in patients operated for GCA of the thoracic aorta. METHODS: A retrospective review of patients operated for GCA of the thoracic aorta was conducted. The diagnosis of GCA was established by the pathology report. RESULTS: Forty consecutive patients (mean age of 66.6 +/- 9.1 years) with a diagnosis of GCA of the thoracic aorta were operated on. A history of polymyalgia rheumatica or temporal arteritis was positive in 22.5% of patients. Emergency surgery was performed in 10% of patients (3 'type A' dissections and 1 'type B'). Mega-aorta syndrome was present in 10% of patients. Involvement of the ascending aorta was present in 100% of patients. One patient had a previous branched thoracic endovascular replacement (TEVAR) with a type I proximal endoleak. In 4 patients, the thoracic aorta was totally replaced. Eighty-five percent of patients had an arch replacement; 79.4% a hemiarch and 20.6% a full arch. The mean circulatory arrest time was 16.3 +/- 12.3 min. Eighty percent of patients had an aortic valve procedure; aortic valve replacement was performed in 50% of them and Bentall-De Bono/valve sparing in 50%. Cerebrovascular accident occurred in 2.5% of patients. No patient died during hospitalization. The mean hospital stay was 8.7 +/- 3.0 days. The mean postoperative follow-up time was 4.2 +/- 2.3 years, with a mean of 4.2 +/- 2.2 thoraco-abdominal computed tomographies (CTs)/patient. Four patients had late reinterventions: 2 were valve-related, 1 for a distal type I endoleak treated with a distal TEVAR extension and 1 type II open thoraco-abdominal replacement for disease progression. One distal type I TEVAR endoleak was treated medically. Aortic diameter progressions on CT (mm/year) were 0.7 +/- 1.0 mm for the arch, 1.2 +/- 2.0 mm for the isthmus, 1.1 +/- 1.7 mm for the mid-descending, 0.7 +/- 0.9 mm for the aortic hiatus, 0.5 +/- 0.5 mm for the supra-renal aorta and 0.6 +/ 0.6 mm for the infra-renal aorta. One patient who declined reoperation on the descending aorta died suddenly 3 years after her initial operation. The 5-year overall survival rate was 91%. CONCLUSIONS: GCA of the thoracic aorta may be suspected in less than 25% of patients preoperatively. Clinical presentation may be acute or chronic with localized or diffused aortic involvement but always involved the ascending aorta. Surgery may be performed with excellent outcomes. Follow-up imaging is mandatory to assess aortic progression. PMID- 27005974 TI - The management of the diaphragm during radical surgery for malignant pleural mesothelioma. AB - OBJECTIVES: Macroscopic complete resection with lung preservation is the objective of radical management of pleural mesothelioma (MPM). Total removal of visceral and parietal pleura (pleurectomy/decortication) almost invariably proceeds to an extended pleurectomy/decortication (EPD) to ensure macroscopic complete resection. We suspected this may not always be necessary. METHODS: We reviewed 314 patients, 86.0% male, median age 62 years (range 14-81 years) undergoing radical surgery for MPM from 1999 to 2014, by either EPD or extrapleural pneumonectomy. The extent of diaphragmatic muscle involvement was recorded from postoperative pathology. Patients were divided into three groups: no involvement, non-transmural, transmural diaphragmatic invasion. RESULTS: A total of 213 (68%) patients underwent EPD, 237 (75.5%) had epithelioid disease and 57.6% were node positive. There was no difference between the three groups in terms of age, cell type, laterality, neoadjuvant chemotherapy and operation. There was a higher degree of diaphragm involvement in females (P = 0.01) and in patients with positive lymph nodes (P = 0.01). No evidence of diaphragmatic involvement was found following pathological assessment of the resection specimen in 119 patients (37.9%). The incidence of abdominal disease progression was 23.9%. There was no correlation with degree of diaphragmatic invasion (rho = 0.01 P = 0.88). Overall survival of those with abdominal progression was similar to those with progression elsewhere: 14.5 vs 13.0 months (P = 0.79), and with those with no progression (16.7 months, P = 0.189). There was no difference in survival when stratified by diaphragmatic involvement (P = 0.44). CONCLUSIONS: In our cohort, there was no evidence of diaphragmatic invasion in over 30% of patients, and we have also failed to find evidence that peritoneal disease progression affects overall survival following radical management. It may therefore theoretically be unnecessary to resect the diaphragm in all cases, and a pleurectomy-decortication could suffice. However, there is an unknown risk of R2 resection which would prejudice survival, and as such we would advocate resecting the diaphragm in all cases to avoid an R2 resection. PMID- 27005976 TI - Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk? AB - OBJECTIVES: Patients with malignant pleural mesothelioma (MPM) eligible for extrapleural pneumonectomy (EPP) may benefit from induction chemotherapy (CT) as historically described, or from induction-accelerated hemithoracic intensity modulated radiation therapy (IMRT) as a potential alternative. However, the impact of the type of induction therapy on postoperative morbidity and mortality remains unknown. METHODS: We performed a retrospective study including every patient who underwent EPP for MPM in our institution between January 2001 and December 2014. Patients without induction treatment (n = 7) or undergoing both induction CT and IMRT (n = 2) were then excluded. The remaining patients (study group) were divided according to the type of induction treatment in Group 1-CT and Group 2-IMRT. Major complications were defined by complications of Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 guidelines. Red blood cell (RBC) transfusion was analysed as a number of packs, and dichotomized as <3 vs >=3 packs. Plasma and platelet transfusion were analysed as a number of units, and dichotomized as no transfusion versus any plasma or platelet transfusion. RESULTS: Altogether, 126 patients (mean age 61.3 +/- 8.1 years, males 82.5%, right side 60.3%, 90-day mortality rate 4.8%) accounted for the study group. Sixty-four patients were included in Group 1-CT and 62 patients were included in Group 2-IMRT. When compared with Group 1-CT, Group 2-IMRT was characterized by older patients (59.3 +/- 9.2 vs 63.3 +/- 8.3 years, P = 0.012), more right-sided resections (46.8 vs 74.1%, P = 0.003), more advanced disease (pathological stage IV: 28.1 vs 53.2%, P = 0.007), less RBC transfusions (5.1 +/- 3.0 vs 3.0 +/- 2.4 packs, P < 0.001), less plasma or platelet transfusions (31.2 vs 9.6%, P = 0.005) and similar rate of major complications (29.6 vs 35.4%, P = 0.614). The 90-day mortality rate was 6.2% in Group 1-CT (n = 4) and 3.2% in Group 2-RT (n = 2, P = 0.680). Induction with IMRT was significantly associated with a decreased risk of transfusion with RBCs [odds ratio (OR) = 0.10, 95% confidence interval (CI) 0.04-0.23, P < 0.001] as well as plasma and platelets (OR = 0.25, 95% CI 0.086-0.67, P = 0.008). CONCLUSIONS: In this large single-centre series of EPP for MPM, the implementation of induction IMRT was not associated with any significant increase in the surgical risks above and beyond induction CT. The switch from induction CT to induction IMRT was associated with resection in older patients with more advanced tumours, less transfusion requirements, comparable postoperative morbidity and 90-day mortality. PMID- 27005977 TI - Psf3 is a prognostic biomarker in lung adenocarcinoma: a larger trial using tissue microarrays of 864 consecutive resections. AB - OBJECTIVES: Partner of Sld five (Psf) 3 is a member of the evolutionarily conserved heterotetrameric complex GINS (Go-Ichi-Ni-San). We previously reported that Psf3 could serve as a biomarker of poor prognosis in lung adenocarcinoma. Here, we used tissue microarrays to analyse Psf3 expression in lung adenocarcinoma and investigated whether its expression is associated with survival outcomes. METHODS: The study included 864 consecutive patients with lung adenocarcinoma who underwent complete resection at Hyogo Cancer Center between January 2002 and December 2009. Tissue microarrays were prepared, and Psf3 was detected using mouse antihuman Psf3 primary monoclonal antibodies. The status of Psf3 expression was determined using these microarrays. RESULTS: Of the 864 patients, 375 had high-positive Psf3 expression and 489 had low-positive expression. Psf3 expression was significantly associated with age, sex, T factor, lymph node metastasis, stage and P factor. The 5-year disease-free survival (DFS) rate was significantly lower in patients with high-positive Psf3 expression than in those with low-positive expression, and Psf3 expression, sex, age, T factor and lymph node metastasis were identified as independent and significant prognostic determinants. Among patients with Stage I adenocarcinoma, the 5-year DFS rate was significantly lower in those with high-positive Psf3 expression than in those with low-positive expression, and Psf3 expression was the most powerful survival predictor. CONCLUSIONS: The present findings strengthened our previous data demonstrating that high Psf3 expression in primary lung adenocarcinoma plays an important role in disease progression and is a prognostic indicator, particularly in early-stage adenocarcinoma. PMID- 27005978 TI - Durability of bioprostheses for the tricuspid valve in patients with congenital heart disease. AB - OBJECTIVES: Only little data exist on the durability of bioprostheses in the tricuspid position in patients with congenital heart disease (CHD). The aim of the study was to determine the reoperation rate and the valve function after primary implantation. METHODS: Between 1990 and 2013, 51 patients with CHD underwent tricuspid valve (TV) replacement with a bioprosthesis. The median age at operation was 32 years (range: 8-69). The underlying morphology was Ebstein's anomaly in 62% of the patients. Implanted valves included 38 pericardial and 13 porcine valves. All available echocardiographic examinations (n = 714) and clinical data were retrospectively reviewed. Dysfunction was defined as an at least moderate regurgitation or a mean diastolic gradient >=9 mmHg. Freedom from death, reoperation and prosthetic valve dysfunction was estimated using the Kaplan-Meier method. RESULTS: The 30-day mortality rate was 9%. The estimated survival rate was 86% at one and 80% at ten years. The freedom from reoperation at 1, 5 and 10 years was 100, 86 and 81%, and that from prosthesis dysfunction detected by echocardiography at 1, 5 and 10 years was 89, 66 and 58%, respectively. The main reason for dysfunction was insufficiency (89%). Valve implantation at an age below 16 years was associated with earlier reoperation and dysfunction (the 5-year freedom rate from reoperation/dysfunction was 70%/30% compared with 89%/78% in the rest of the patients, P = 0.016/0.0009). CONCLUSIONS: Serial echocardiography shows a high rate of dysfunction of TV bioprosthesis in patients with CHD, which already occurred a few years after implantation. In patients below 16 years of age, most prostheses are dysfunctional within 5 years. PMID- 27005979 TI - Comparison of logistic EuroSCORE and EuroSCORE II in predicting operative mortality of 1125 total arterial operations. AB - OBJECTIVES: The purpose of this study was to compare effectiveness of the 1999 logistic EuroSCORE (LES) and of the 2012 EuroSCORE II (ESII) in a real-world patient population of 1125 patients undergoing total arterial grafting (TAG) coronary artery bypass graft (CABG) surgery. METHODS: The performance of the two risk scores was compared using (i) discrimination (accuracy of discriminating non survivors from survivors), (ii) calibration (assessment of agreement between the predicted/observed outcomes) and (iii) agreement between the two scores. By averaging medians of LES and ESII and then sub-division into 10 equal groups, actual operative mortality rate was compared with the median LES and ESII within each risk group, the difference plotted against the average risk score (as in a Bland and Altman plot), and using the traditional risk groupings for EuroSCORE of low (0-2.99), medium (3-5.99) and high risk (6.0 and above), the reclassification rate of ESII was compared with that of LES. RESULTS: In 1125 consecutive total arterial CABG patients, demographics included: mean age 64.6 years, 79% males, 35% diabetic patients, 57% urgent/emergent patients, 37% off-pump and 77% bilateral mammary grafting. Overall operative mortality was 3.2% (36 patients). Comparison of the LES and ESII showed (i) good discrimination for both LES and ESII (area under the curve for LES was 0.85 and for ESII was 0.87); (ii) neither score was well calibrated: LES tended to overestimate and ESII underestimated risk. In general, the ESII provided a better estimate of risk in lower risk patients and LES was better for the highest risk group. (iii) In terms of agreement, in the lower four risk groups the risk was overestimated by both scores, in five of the higher six risk groups ESII underestimated risk and LES overestimated risk, and in the highest risk group LES was very close (17.2 cf. 17.7) compared with ESII (5.6 cf. 17.7). In addition, ESII downgraded risk in 96.8% of survivors and in 97.2% of non-survivors. CONCLUSIONS: In 1125 consecutive TAG CABG patients, neither LES nor ESII performed well enough to be used as a consistent risk stratification tool; LES overestimated risk but was highly accurate for the highest of 10 risk groups and ESII consistently underestimated risk in all patients. PMID- 27005980 TI - No clinical effect of prosthesis-patient mismatch after transcatheter versus surgical aortic valve replacement in intermediate- and low-risk patients with severe aortic valve stenosis at mid-term follow-up: an analysis from the NOTION trial. AB - OBJECTIVES: Prosthesis-patient mismatch (PPM) after surgical aortic valve replacement (SAVR) for severe aortic valve stenosis (AVS) is common, but less common after transcatheter aortic valve replacement (TAVR) in patients considered at high risk for death after surgery. The objectives of this study were to determine incidence and clinical effect of PPM after SAVR and TAVR in a primarily low-risk patient group. METHODS: Patients 70 years or older with severe isolated AVS, regardless of predicted operative mortality risk, were consecutively randomized 1:1 to TAVR using a self-expandable bioprosthesis (n = 145) or SAVR (n = 135). Post-procedure PPM was graded after 3 months as follows: Not present mild, if indexed effective orifice area (iEOA) >0.85 cm2/m2, moderate, if 0.65 cm2/m2 < iEOA <= 0.85 cm2/m2 and severe, if iEOA <=0.65 cm2/m2. Outcomes were major adverse cardiac and cerebrovascular events (MACCE, e.g. composite rate of all-cause death, stroke, myocardial infarction or valve reintervention), cardiac related hospitalizations and New York Heart Association (NYHA) functional class after 2 years. RESULTS: The incidence and the severity of PPM were significantly lower after TAVR compared with SAVR (severe, moderate, none-mild 14.0, 35.5, 50.4 vs 33.9, 36.7, 29.4%; P<0.001). PPM resulted in similar higher mean valve gradients at 3 months for both groups. Baseline characteristics related to severe PPM were younger age, absence of diabetes mellitus, lower mortality-risk score for TAVR, and younger age and higher body mass index for SAVR. At 2 years, there were numerical but no statistically significant differences between both TAVR and SAVR patients with severe and no severe PPM for MACCE (0.0 vs 12.8% for TAVR; P = 0.13, and 13.5 vs 7.0% for SAVR; P = 0.27), number of cardiac-related hospitalizations (mean +/- standard deviation 0.4 +/- 0.6 vs 0.6 +/- 0.8; P = 0.23, and 0.4 +/- 0.8 vs 0.5 +/- 0.9; P = 0.70) and NYHA functional class (Class I/II/III/IV: 64.7/29.4/5.9/0.0 vs 62.1/34.7/3.2/0.0%, respectively; P = 0.91, and 71.4/25.7/2.9/0.0 vs 72.9/22.9/4.3/0.0%, respectively; P = 0.92). CONCLUSIONS: The incidence of PPM was lower and less severe after TAVR compared with SAVR in intermediate- and low-risk patients with severe AVS. There were no significant differences in MACCE, cardiac-related hospitalizations or NYHA class after 2 years for patients with versus those without severe PPM. PMID- 27005981 TI - Implanting permanent left ventricular assist devices in patients on veno-arterial extracorporeal membrane oxygenation support: do we really need a cardiopulmonary bypass machine? AB - OBJECTIVES: Selected patients who failed to be weaned off temporary veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support may be considered for long term left ventricular assist devices (LVADs). Activation of the systemic inflammatory response due to the cardiopulmonary bypass (CPB) machine and its associated deleterious effects on the coagulation system have been well documented. The aim of the study was to compare the outcome of patients receiving VAD on VA-ECMO with patients who were converted to CPB at the time of VAD implantation. METHODS: Data of patients undergoing LVAD implantation between January 2010 and September 2015 were retrospectively reviewed. Inclusion criteria were patients with prior VA-ECMO. Perioperative characteristics and postoperative outcome of patients who received LVAD after VA-ECMO with (CPB group) or without CPB (no-CPB group) were compared. RESULTS: A total of 110 permanent VADs were implanted during this time frame. Forty patients had VA-ECMO prior to VAD implantation and met the inclusion criteria. The CPB was used in 23 patients and 17 patients received VAD on VA-ECMO without using CPB. The preoperative characteristics of the patients were comparable except for lower body mass index, higher international normalized ratio (INR) and higher rate of preoperative intra aortic balloon pump usage in the CPB group (P = 0.035, 0.008 and 0.003, respectively). The incidence of postoperative right VAD implantation and survival rate was comparable between both groups. However, the chest tube blood loss and amount of blood product usage was higher in the CPB group. The total blood loss in the first 24 h after surgery (2469 +/- 2067 vs 1080 +/- 941 ml, P= 0.05) and number of units of intraoperative fresh frozen plasma administered (4 +/- 3 vs 1 +/- 2, P= 0.02) remained higher in the CPB group even after adjustment for differences in preoperative INR value by propensity score matching. CONCLUSIONS: This study demonstrates that the CPB machine can be safely omitted when a long term VAD is implanted on VA-ECMO support. Blood loss in the first 24 h after surgery was less and a significantly lower number of blood products were necessary in these patients compared with patients in whom the CPB machine was used. However, similar survival rates between these two groups were observed. PMID- 27005982 TI - Uterine cervical adenocarcinoma metastasizing concurrently to eutopic and ectopic ovaries: A case report. AB - Ectopic ovary, a designation that includes supernumerary ovaries and accessory ovaries, is a rare gonadal anomaly. We encountered a patient with a metastasis to such an anomaly and herein provide a review of the published work. A 43-year-old woman was diagnosed with stage IIb cervical adenocarcinoma with suspicion for a right ovarian malignancy. She underwent laparotomy after completing three cycles of neoadjuvant chemotherapy. Intraoperative inspection revealed two normal ovaries, but an ovary-like structure was identified attached to the fimbriae of the left fallopian tube. A cystic tumor, 12 cm in diameter, developed from this structure, which was not connected to the infundibulopelvic ligament. The mass was pulled and elevated into the right pelvis by omental adhesions. Pathological examination revealed uterine cervical endometrioid adenocarcinoma with deep stromal invasion, vaginal invasion, and pelvic lymph-node metastases. Both the left eutopic ovary and the ovary-like structure contained endometrioid adenocarcinoma metastases. The ovary-like structure contained spindle-shaped theca cells, which were positive for inhibin alpha; therefore, this structure was defined as ovarian tissue. The final diagnosis was well-differentiated uterine cervical endometrioid adenocarcinoma with metastases to the pelvic lymph nodes and to the left eutopic and ectopic ovaries (pT2a2N1M0). To the best of our knowledge, there have been no previous descriptions in the English-language published work of uterine cervical adenocarcinoma metastasizing concurrently to unilateral eutopic and ectopic ovaries. (c) 2016 Japan Society of Obstetrics and Gynecology. PMID- 27005983 TI - Palladium-atom catalyzed formic acid decomposition and the switch of reaction mechanism with temperature. AB - Formic acid decomposition (FAD) reaction has been an innovative way for hydrogen energy. Noble metal catalysts, especially palladium-containing nanoparticles, supported or unsupported, perform well in this reaction. Herein, we considered the simplest model, wherein one Pd atom is used as the FAD catalyst. With high level theoretical calculations of CCSD(T)/CBS quality, we investigated all possible FAD pathways. The results show that FAD catalyzed by one Pd atom follows a different mechanism compared with that catalyzed by surfaces or larger clusters. At the initial stage of the reaction, FAD follows a dehydration route and is quickly poisoned by CO due to the formation of very stable PdCO. PdCO then becomes the actual catalyst for FAD at temperatures approximately below 1050 K. Beyond 1050 K, there is a switch of catalyst from PdCO to Pd atom. The results also show that dehydration is always favoured over dehydrogenation on either the Pd-atom or PdCO catalyst. On the Pd-atom catalyst, neither dehydrogenation nor dehydration follows the formate mechanism. In contrast, on the PdCO catalyst, dehydrogenation follows the formate mechanism, whereas dehydration does not. We also systematically investigated the performance of 24 density functional theory methods. We found that the performance of the double hybrid mPW2PLYP functional is the best, followed by the B3LYP, B3PW91, N12SX, M11, and B2PLYP functionals. PMID- 27005985 TI - Fellows of the RCN. PMID- 27005984 TI - E-Cigarette Design Preference and Smoking Cessation: A U.S. Population Study. AB - INTRODUCTION: Electronic cigarette (e-cigarette) designs may be described as "closed" or "open." Closed systems are disposable or reloadable with prefilled cartridges (cigalikes). Open systems feature a prominent chamber (tank), refillable with e-liquid. This study examined user design preference and its association with smoking cessation. METHODS: A probability sample of current e cigarette users (n=923) among adult ever smokers (n=6,560) in the U.S. was surveyed online between February 28 and March 31, 2014, and analyzed in September 2014. Photos of e-cigarette devices were presented alongside survey questions to facilitate respondents' understanding of the questions. RESULTS: Most e-cigarette users were exclusive users of one design: 51.4% used only closed systems and 41.1% used only open systems, with 7.4% using both. Former smokers were more likely to use open systems than current smokers (53.8% vs 35.2%, p=0.002). Current smokers who attempted to quit in the last 12 months were more likely to use open systems than those who did not (41.4% vs 27.7%, p=0.029). Open system users were more likely than closed system users to use e-cigarettes daily (50.2% vs 22.9%, p<0.0001). Open system users were less likely to report their devices resembled (3.1% vs 73.0%, p<0.0001) or tasted like (29.1% vs 53.3%, p<0.0001) a cigarette but were more likely to report that their devices satisfied cravings than closed system users (82.8% vs 67.2%, p=0.001). CONCLUSIONS: Preference of e cigarette design is associated with smoking cessation. A device's ability to deliver more nicotine and its flexibility in use might contribute to users' success in quitting smoking. PMID- 27005986 TI - Surface plasmon resonance spectroscopy of single bowtie nano-antennas using a differential reflectivity method. AB - We report on the structural and optical properties of individual bowtie nanoantennas both on glass and semiconducting GaAs substrates. The antennas on glass (GaAs) are shown to be of excellent quality and high uniformity reflected by narrow size distributions with standard deviations for the triangle and gap size of = 4.5 nm = 2.6 nm and = 5.4 nm = 3.8 nm, respectively. The corresponding optical properties of individual nanoantennas studied by differential reflection spectroscopy show a strong reduction of the localised surface plasmon polariton resonance linewidth from 0.21 eV to 0.07 eV upon reducing the antenna size from 150 nm to 100 nm. This is attributed to the absence of inhomogeneous broadening as compared to optical measurements on nanoantenna ensembles. The inter-particle coupling of an individual bowtie nanoantenna, which gives rise to strongly localised and enhanced electromagnetic hotspots, is demonstrated using polarization-resolved spectroscopy, yielding a large degree of linear polarization of rhomax ~ 80%. The combination of highly reproducible nanofabrication and fast, non-destructive and non-contaminating optical spectroscopy paves the route towards future semiconductor-based nano-plasmonic circuits, consisting of multiple photonic and plasmonic entities. PMID- 27005987 TI - Distribution and diversity of bacterial communities and sulphate-reducing bacteria in a paddy soil irrigated with acid mine drainage. AB - AIMS: To investigate the effects of long-term acid mine drainage (AMD) irrigation on the change in bacterial community and sulphate-reducing bacteria (SRB) in a paddy soil. METHODS AND RESULTS: The bacterial community structures were investigated using 454 pyrosequencing, and 98 931 effective sequences were selected for the bacterial diversity analysis. The known dominant phyla in the paddy soil were Acidobacteria (33.5%), Proteobacteria (19.7%), Nitrospira (2.8%) and Actinobacteria (2.7%). Higher percentage of Acidobacteria than Proteobacteria was detected. The relative abundances of the dominant bacterial lineages were more significantly correlated with the soil pH, the organic matter and the sulphate than the heavy metals. The diversity of the SRB in the surface paddy soil showed that the uncultured SRB groups might play important roles in paddy soils. The other OTUs mainly belonged to six phylogenetic divisions: Desulfobacca, Desulfovibrio, Syntrophobacter, Desulforhopalus, Desulfarculus and Desulfobulbus. The distribution of the absolute abundance and the relative contribution of the SRB along the vertical soil profile were investigated by RT PCR assays based on the dsrB gene. The abundance of the dsrB gene copy numbers was up to 1.92 * 10(9) copies g(-1) dry soil, which is slightly higher than the other non-AMD-affected paddy soil. CONCLUSIONS: This study demonstrated that the abundance of SRB is increased by the AMD irrigation while changing the composition and diversity of the bacterial community in the paddy soil. SIGNIFICANCE AND IMPACT OF THE STUDY: This is, to our knowledge, the first attempt to characterize and quantify changes in the diversity and distribution of the microbial community and SRB in the long-term AMD-irrigated paddy soil, which will further increase our understanding of the impact of AMD on sulphur biogeochemical cycling in the paddy soil. PMID- 27005988 TI - Cortical Development Requires Mesodermal Expression of Tbx1, a Gene Haploinsufficient in 22q11.2 Deletion Syndrome. AB - In mammals, proper temporal control of neurogenesis and neural migration during embryonic development ensures correct formation of the cerebral cortex. Changes in the distribution of cortical projection neurons and interneurons are associated with behavioral disorders and psychiatric diseases, including schizophrenia and autism, suggesting that disrupted cortical connectivity contributes to the brain pathology. TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS), a chromosomal deletion disorder characterized by a greatly increased risk for schizophrenia. We have previously shown that Tbx1 heterozygous mice have reduced prepulse inhibition, a behavioral abnormality that is associated with 22q11.2DS and nonsyndromic schizophrenia. Here, we show that loss of Tbx1 disrupts corticogenesis in mice by promoting premature neuronal differentiation in the medio-lateral embryonic cortex, which gives rise to the somatosensory cortex (S1). In addition, we found altered polarity in both radially migrating excitatory neurons and tangentially migrating inhibitory interneurons. Together, these abnormalities lead to altered lamination in the S1 at the terminal stages of corticogenesis in Tbx1 null mice and similar anomalies in Tbx1 heterozygous adult mice. Finally, we show that mesoderm-specific inactivation of Tbx1 is sufficient to recapitulate the brain phenotype indicating that Tbx1 exerts a cell nonautonomous role in cortical development from the mesoderm. PMID- 27005989 TI - Brain-Derived Neurotrophic Factor Val66Met Polymorphism Affects the Relationship Between an Anxiety-Related Personality Trait and Resting Regional Cerebral Blood Flow. AB - Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress responses mediated by limbic frontotemporal circuits, and its gene contains a functional polymorphism (Val66Met) that may influence trait stress sensitivity. Reports of an association of this polymorphism with anxiety related personality traits have been controversial and without clear neurophysiological support. We, therefore, determined the relationship between resting regional cerebral blood flow (rCBF) and a well-validated measure of anxiety-related personality, the TPQ Harm Avoidance (HA) scale, as a function of BDNF Val66Met genotype. Sixty-four healthy participants of European ancestry underwent resting H215O positron emission tomography scans. For each genotype group separately, we first determined the relationship between participants' HA scores and their resting rCBF values in each voxel across the entire brain, and then directly compared these HA-rCBF relationships between Val66Met genotype groups. HA-rCBF relationships differed between Val homozygotes and Met carriers in several regions relevant to stress regulation: subgenual cingulate, orbital frontal cortex, and the hippocampal/parahippocampal region. In each of these areas, the relationship was positive in Val homozygotes and negative in Met carriers. These data demonstrate a coupling between trait anxiety and basal resting blood flow in frontolimbic neurocircuitry that may be determined in part by genetically mediated BDNF signaling. PMID- 27005991 TI - Multivariate Associations of Fluid Intelligence and NAA. AB - Understanding the neural and metabolic correlates of fluid intelligence not only aids scientists in characterizing cognitive processes involved in intelligence, but it also offers insight into intervention methods to improve fluid intelligence. Here we use magnetic resonance spectroscopic imaging (MRSI) to measure N-acetyl aspartate (NAA), a biochemical marker of neural energy production and efficiency. We use principal components analysis (PCA) to examine how the distribution of NAA in the frontal and parietal lobes relates to fluid intelligence. We find that a left lateralized frontal-parietal component predicts fluid intelligence, and it does so independently of brain size, another significant predictor of fluid intelligence. These results suggest that the left motor regions play a key role in the visualization and planning necessary for spatial cognition and reasoning, and we discuss these findings in the context of the Parieto-Frontal Integration Theory of intelligence. PMID- 27005992 TI - An update on the management of hepatitis C virus-infected patients with stage 4-5 chronic kidney disease while awaiting the revised KDIGO Guidelines. AB - The treatment of hepatitis C virus (HCV) infection has progressed markedly over the last 2 decades, with a dramatic acceleration the last 3 years. The combination of two or three direct-acting antiviral drugs (DAAs) targeting viral proteins [NS3/4A protease inhibitors, NS5B nucleos(t)idic and non-nucleos(t)idic polymerase inhibitors, NS5A replication complex inhibitors], with or without ribavirin but without interferon (interferon-free regimen), for 8-24 weeks, achieved high sustained virological response (>90%), whatever fibrosis stage, genotype and subtype, baseline viral load, prior therapeutic history of the patient (naive or experienced) and pre-existing resistance-associated variants with a fair tolerance and reduced pill burden. International guidelines recommend to ideally treat all infected patients even if a prioritization of the most severe patients (extensive fibrosis or cirrhosis, symptomatic cryoglobulinaemic vasculitis...) appears to be the best cost-effective and urgent policy. Patients with stage 4-5 chronic kidney disease (CKD) have to be considered as priority patients. Updating of the Kidney Disease: Improving Global Outcomes recommendations is due to start soon, but awaiting their availability, we present here an overview of recent developments in the field. PMID- 27005994 TI - Lack of evidence does not justify neglect: how can we address unmet medical needs in calciphylaxis? AB - Calcific uraemic arteriolopathy (CUA), or calciphylaxis, is a rare disease predominantly occurring in comorbidity with dialysis. Due to the very low frequency of CUA, prospective studies on its management are lacking and even anecdotal reports on treatment remain scarce. Therefore, calciphylaxis is still a challenging disease with dismal prognosis urgently requiring adequate strategies for diagnosis and treatment.In an attempt to fill some of the current gaps in evidence on various, highly debated and controversial aspects of dialysis associated calciphylaxis, 13 international experts joined the 1st Consensus Conference on CUA, held in Leuven, Belgium on 21 September 2015. The conference was supported by the European Calciphylaxis Network (EuCalNet), which is a task force of the ERA-EDTA scientific working group on Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD). After an intense discussion, a 9-point Likert scale questionnaire regarding 20 items on calciphylaxis was anonymously answered by each participant. These 20 items addressed unsolved issues in terms of diagnosis and management of calciphylaxis. On the one hand, the analysis of the expert opinions identified areas of general consensus, which might be a valuable aid for physicians treating such a disease with less experience in the field. On the other hand, some topics such as the pertinence of skin biopsy and administration of certain treatments revealed divergent opinions. The aim of the present summary report is to provide some guidance for clinicians who face patients with calciphylaxis in the current setting of absence of evidence-based medicine. PMID- 27005990 TI - eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures. AB - Alterations in the balance of inhibitory and excitatory synaptic transmission have been implicated in the pathogenesis of neurological disorders such as epilepsy. Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation. Here, we show that eEF2K activity negatively regulates GABAergic synaptic transmission. Indeed, loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and alpha5-containing GABAA receptors and thus interferes with the excitation/inhibition balance. This cellular phenotype is accompanied by an increased resistance to epilepsy and an impairment of only a specific hippocampal-dependent fear conditioning. From a clinical perspective, our results identify eEF2K as a potential novel target for antiepileptic drugs, since pharmacological and genetic inhibition of eEF2K can revert the epileptic phenotype in a mouse model of human epilepsy. PMID- 27005995 TI - Neutrophil to lymphocyte ratio as an indicator of the malignant behaviour of hepatocellular carcinoma. AB - BACKGROUND: The preoperative serum neutrophil to lymphocyte ratio (NLR) has been associated with survival in patients with hepatocellular carcinoma (HCC). However, it is still unclear what the NLR reflects precisely. This study aimed to elucidate the relationship between the NLR and TNM stage, and the role of NLR as a prognostic factor after liver resection for HCC. METHODS: This retrospective study enrolled patients who underwent liver resection as initial treatment for HCC. The best cut-off value of serum NLR was determined, and overall survival was compared among patients grouped according to TNM stage (I, II and III). RESULTS: The best cut-off value for NLR was 2.8. A high preoperative NLR was more frequently associated with poor overall survival than a low preoperative NLR after resection for TNM stage I tumours (5-year survival 45.0 versus 76.4 per cent, P < 0.001), but not stage II (P = 0.283) or stage III (P = 0.155) tumours. Among patients with TNM stage I disease, the proportion of patients with extrahepatic recurrence was greater in the group with a high preoperative NLR than in the low-NLR group (P = 0.006). In multivariable analysis, preoperative NLR was the strongest independent prognostic risk factor for overall survival in TNM stage I (hazard ratio 2.69, 95 per cent c.i. 1.57 to 4.59; P < 0.001). CONCLUSION: Preoperative NLR was an important prognostic factor for TNM stage I HCC after liver resection with curative intent. These results suggest that the NLR may reflect the malignant potential of HCC. PMID- 27005996 TI - Angioedema with renin angiotensin system drugs and neutral endopeptidase inhibitors. PMID- 27005997 TI - An evaluation of the Open and Honest Care Programme in acute NHS trusts in Northern England. AB - AIM: To explore the impact of the National Health Service England's Open and Honest Care Programme on patient safety, patient and staff experience and improvement practices within acute National Health Service settings. BACKGROUND: The Open and Honest Care Programme forms a key tenet of the Nursing Midwifery and Care Staff Strategy launched by the Department of Health in England and Wales in 2012. METHODS: An electronic survey (n = 387) was administered to National Health Service staff. Semi-structured telephone interviews (n = 13) were conducted with senior nurses and ward managers. RESULTS: Over 70% of the survey respondents agreed that the programme increased transparency with the public about the quality of care, helped the working experience of National Health Service staff and improved patient safety respectively. Interviews revealed the Open and Honest Care Programme had enabled National Health Service staff to appraise the effectiveness of their improvement efforts. CONCLUSION: The Open and Honest Care Programme could be an important part of the National Health Service Improvement Strategy. The collection of metric and narrative information highlighted where patient-centred improvements were required, facilitating the targeting and development of specific interventions or resources. IMPLICATIONS FOR NURSING MANAGEMENT: The results indicate that the programme may assist managers to identify areas for improvement and that programmes such as this deserve consideration by health-care management globally. PMID- 27005998 TI - Bimetallic C-C Bond-Forming Reductive Elimination from Nickel. AB - Ni-catalyzed cross-coupling reactions have found important applications in organic synthesis. The fundamental characterization of the key steps in cross coupling reactions, including C-C bond-forming reductive elimination, represents a significant challenge. Bimolecular pathways were invoked in early proposals, but the experimental evidence was limited. We present the preparation of well defined (pyridine-pyrrolyl)Ni monomethyl and monophenyl complexes that allow the direct observation of bimolecular reductive elimination to generate ethane and biphenyl, respectively. The sp(3)-sp(3) and sp(2)-sp(2) couplings proceed via two distinct pathways. Oxidants promote the fast formation of Ni(III) from (pyridine pyrrolyl)Ni-methyl, which dimerizes to afford a bimetallic Ni(III) intermediate. Our data are most consistent with the subsequent methyl coupling from the bimetallic Ni(III) to generate ethane as the rate-determining step. In contrast, the formation of biphenyl is facilitated by the coordination of a bidentate donor ligand. PMID- 27006000 TI - Pharmacokinetics of acyclovir in a morbidly obese patient with renal impairment. PMID- 27005999 TI - Development of ZMYM2-FGFR1 driven AML in human CD34+ cells in immunocompromised mice. AB - Acute myelogenous leukemia (AML) has an overall poor survival rate and shows considerable molecular heterogeneity in its etiology. In the WHO classification there are >50 cytogenetic subgroups of AML, many showing highly specific chromosome translocations that lead to constitutive activation of individual kinases. In a rare stem cell leukemia/lymphoma syndrome, translocations involving 8p11 lead to constitutive activation of the fibroblast growth factor receptor 1 (FGFR1) kinase. This disorder shows myeloproliferative disease with almost invariable progresses to AML and conventional therapeutic strategies are largely unsuccessful. Because of the rare nature of this syndrome, models that faithfully recapitulate the human disease are needed to evaluate therapeutic strategies. The t(8;13)(p11;q12) chromosome translocation is most common rearrangement seen in this syndrome and creates a ZMYM2-FGFR1 chimeric kinase. To understand more about the molecular etiology of AML induced by this particular rearrangement, we have created a model human CD34+ cells transplanted into immunocompromized mice which develop myeloproliferative disease that progresses to AML with a long (>12 months) latency period. As in humans, these mice show hepatospenomegaly, hypercellular bone marrow and a CD45 + CD34 + CD13+ immunophenotype. Molecular studies demonstrate upregulation of genes such as KLF4 and FLT3 that promote stemness, and overexpression of MYC, which is associated with suppression of myeloid cell differentiation. This murine model, therefore, provides an opportunity to develop therapeutic strategies against the most common subtype within these FGFR1 driven neoplasms and study the molecular etiology in more depth. PMID- 27006001 TI - Multimodal micro, nano, and size conversion ultrasound agents for imaging and therapy. AB - Ultrasound (US) is one of the most commonly used clinical imaging techniques. However, the use of US and US-based intravenous agents extends far beyond imaging. In particular, there has been a surge in the fabrication of multimodality US contrast agents and theranostic US agents for cancer imaging and therapy. The unique interaction of US waves with microscale and nanoscale agents has attracted much attention in the development of contrast agents and drug delivery vehicles. The dimensions of the agent not only dictate how it behaves in vivo, but also how it interacts with US for imaging and drug delivery. Furthermore, these agents are also unique due to their ability to convert from the nanoscale to the microscale and vice versa, having imaging and therapeutic utility in both dimensions. Here, we review multimodality and multifunctional US based agents, according to their size, and also highlight recent developments in size conversion US agents. WIREs Nanomed Nanobiotechnol 2016, 8:796-813. doi: 10.1002/wnan.1398 For further resources related to this article, please visit the WIREs website. PMID- 27006002 TI - Factors associated with the onset and progression of neurotrauma: A systematic review of systematic reviews and meta-analyses. AB - Neurotrauma, including traumatic brain injury (TBI) and spinal cord injury (SCI), is a preventable condition that imposes an important burden on the Canadian society. In this study, the current evidence on risk factors for the onset and progression of neurotrauma is systematically reviewed and synthesized. Searches of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Medline and Medline in Process (via OVID), EMBASE and PsycINFO from inception to February 2013 were conducted to identify relevant systematic reviews and meta-analyses published in English or French. Two referees screened and assessed the quality of the studies using the AMSTAR tool. Thirty-two studies examined at least one risk factor for the onset of neurotrauma. Thirteen studies passed the quality assessment and the majority evaluated the impact of protective equipment in sports. Helmets effectively reduce TBI from bicycling, skiing, snowboarding, ice hockey and motorcycling. There was no evidence of a protective effect of helmets for SCI. No studies contributed evidence on risk factors for the onset of SCI. Of two studies examining risk factors for the progression of neurotrauma, only injury severity was found to be associated with poorer post injury outcomes. Substantial evidence supports the use of helmets for the prevention of TBI in sports and motorcycling and face shields in ice hockey. Addressing bicycle helmet legislation across Canada may be an effective option for reducing TBI caused by bicycle accidents. Limited evidence on relevant risk factors for spinal cord injuries and neurotrauma progression was available. PMID- 27006003 TI - Spectral and binaural loudness summation for hearing-impaired listeners. AB - Sensorineural hearing loss typically results in a steepened loudness function and a reduced dynamic range from elevated thresholds to uncomfortably loud levels for narrowband and broadband signals. Restoring narrowband loudness perception for hearing-impaired (HI) listeners can lead to overly loud perception of broadband signals and it is unclear how binaural presentation affects loudness perception in this case. Here, loudness perception quantified by categorical loudness scaling for nine normal-hearing (NH) and ten HI listeners was compared for signals with different bandwidth and different spectral shape in monaural and in binaural conditions. For the HI listeners, frequency- and level-dependent amplification was used to match the narrowband monaural loudness functions of the NH listeners. The average loudness functions for NH and HI listeners showed good agreement for monaural broadband signals. However, HI listeners showed substantially greater loudness for binaural broadband signals than NH listeners: on average a 14.1 dB lower level was required to reach "very loud" (range 30.8 to -3.7 dB). Overall, with narrowband loudness compensation, a given binaural loudness for broadband signals above "medium loud" was reached at systematically lower levels for HI than for NH listeners. Such increased binaural loudness summation was not found for loudness categories below "medium loud" or for narrowband signals. Large individual variations in the increased loudness summation were observed and could not be explained by the audiogram or the narrowband loudness functions. PMID- 27006004 TI - Oocyte cryopreservation: where are we now? AB - INTRODUCTION: Since the first live birth from oocyte cryopreservation three decades ago, oocyte cryopreservation has become an important component of ART. Cryopreservation techniques have evolved, leading to higher success rates and the introduction of oocyte cryopreservation into IVF clinics worldwide. Concurrently, there has been an increase in patient demand, especially for so-called 'social egg freezing' that allows women to preserve their fertility in anticipation of age-related fertility decline. This review addresses a need to evaluate the current status of oocyte cryopreservation. It explores current techniques and success rates, clinical applications, the rise of elective oocyte cryopreservation, and future implications. METHODS: A search was performed using Web of Science and PubMed databases for publications between January 1980 and December 2015. Keywords used included 'egg freezing', 'oocyte freezing', 'oocyte cryopreservation', 'oocyte vitrification', and 'fertility preservation'. RESULTS: The success rate of oocyte cryopreservation has risen, and the increasing use of vitrification offers has improved outcomes, with IVF pregnancy rates now similar to those achieved with fresh oocytes. There are conflicting opinions about the comparative success rates of open and closed vitrification. Patients are accessing and receiving oocyte cryopreservation for a wide range of indications, and there has been a marked increase in patient numbers and oocyte cryopreservation cycles. Oocyte cryopreservation for circumventing age-related infertility is becoming more widely accepted. CONCLUSION: Oocyte cryopreservation is an established component of ART, with vitrification now being the cryopreservation technique of choice. Increasing numbers of women undergo oocyte cryopreservation for both medical and social reasons. It is important to continue auditing outcomes and reporting long-term follow-up of children born from frozen thawed oocytes. PMID- 27006006 TI - HLA-A*02:513, a novel HLA-A*02 allele. AB - HLA-A*02:513 shows one nucleotide difference with A*02:07:01 (125G > A). PMID- 27006005 TI - Intrathecal decompression versus epidural decompression in the treatment of severe spinal cord injury in rat model: a randomized, controlled preclinical research. AB - BACKGROUND: In the setting of severe spinal cord injury (SCI), there is no markedly efficacious clinical therapeutic regimen to improve neurological function. After epidural decompression, as is shown in animal models, the swollen cord against non-elastic dura and elevation of intrathecal pressure may be the main causes of aggravated neurologic function. We performed an intrathecal decompression by longitudinal durotomy to evaluate the neuroprotective effect after severe SCI by comparing with epidural decompression. METHODS: Eighty-four adult male Sprague-Dawley rats were assigned to three groups: sham group (group S), epidural decompression (group C), and intrathecal decompression group (group D). A weight-drop model was performed at T9. The Basso-Beattie-Bresnahan (BBB) score was used to evaluate neurological function. Animals were sacrificed at corresponding time points, and we performed pathohistological examinations including HE staining and immunohistochemical staining (IHC) of glial fibrillary acidic protein (GFAP), neurocan, and ED1 at the epicenter of injured cords. Finally, the lesions were quantitatively analyzed by SPSS 22.0. RESULTS: The mortality rates were, respectively, 5.55 % (2/36) and 13.9 % (5/36) in groups C and D, and there was no significant difference between groups C and D (P = 0.214). Compared with epidural decompression, intrathecal decompression could obviously improve BBB scores after SCI. HE staining indicated that more white matter was spared, and fewer vacuoles and less axon degradation were observed. The expression peak of GFAP, neurocan, and ED1 occurred at an earlier time and was down-regulated in group D compared to group C. CONCLUSIONS: Our findings based on rat SCI model suggest that intrathecal decompression by longitudinal durotomy can prompt recovery of neurological function, and this neuroprotective mechanism may be related to the down-regulation of GFAP, neurocan, and ED1. PMID- 27006008 TI - [Use of fetal movements counting for prolonged pregnancy: A comparative preliminary cohort study before and after implementation of an information brochure]. AB - OBJECTIVES: Compare the number of consultations with the consultation's delay in relation with the sensation of decrease active fetal movements (AFM) in case of late pregnancy, according to the fact if the patients use or not the AFM's count. MATERIALS AND METHODS: We have compared a "control" group made up of 160 patients who received a classic information and observation (from December 18th, 2013 to February 28th, 2014) versus an "educated" group made up of 160 patients who have been educated to the AFM count (from March 1st, 2014 to August 12th, 2014). RESULTS: The consultations for AFM decrease, were significantly more frequent in the "control" group than in the "educated" group (36 versus 8, P=0.0009). Inducing labor due to AFM reduction was not statistically different between both groups (13 patients in the "educated group" versus 7 patients in the "control" group P=0.97). CONCLUSION: Learning a count method seems to decrease the number of consultations for AFM reduction without increasing the perinatal morbidity but maybe at the cost of an increase of obstetric interventions. PMID- 27006007 TI - Adapting and testing a brief intervention to reduce maternal anxiety during pregnancy (ACORN): study protocol for a randomised controlled trial. AB - BACKGROUND: National guidelines in the UK, United States of America, Canada, and Australia have recently stressed the importance of identifying and treating antenatal anxiety and depression. However, there is little research into the most effective and acceptable ways of helping women manage their symptoms of anxiety and stress during pregnancy. Research indicates the necessity to consider the unique needs and concerns of perinatal populations to ensure treatment engagement, highlighting the need to develop specialised treatments which could be integrated within routine antenatal healthcare services. This trial aims to develop a brief intervention for antenatal anxiety, with a focus on embedding the delivery of the treatment within routine antenatal care. METHODS/DESIGN: This study is a two-phase feasibility trial. In phase 1 we will develop and pilot a brief intervention for antenatal anxiety, blended with group support, to be led by midwives. This intervention will draw on cognitive behavioural principles and wider learning from existing interventions that have been used to reduce anxiety in expectant mothers. The intervention will then be tested in a pilot randomised controlled trial in phase 2. The following outcomes will be assessed: (1) number of participants meeting eligibility criteria, (2) number of participants consenting to the study, (3) number of participants randomised, (4) number of sessions completed by those in the intervention arm, and (5) number of participants completing the post-intervention outcome measures. Secondary outcomes comprise: detailed feedback on acceptability, which will guide further development of the intervention; and outcome data on symptoms of maternal and paternal anxiety and depression, maternal quality of life, quality of couple relationship, mother-child bonding, infant temperament and infant sleep. DISCUSSION: The study will provide important data to inform the design of a future full-scale randomised controlled trial of a brief intervention for anxiety during pregnancy. This will include information on its acceptability and feasibility regarding implementation within current antenatal services, which will inform whether ultimately this provision could be rolled out widely in healthcare settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95282830 . Registered on 29 October 2014. PMID- 27006009 TI - The impact of being homeless on the unsuccessful outcome of treatment of pulmonary TB in Sao Paulo State, Brazil. AB - BACKGROUND: Tuberculosis (TB) is a major public health problem requiring complex treatment, the success of which depends on biological, social, and institutional factors. Sao Paulo State (SPS), in Brazil, has a high TB burden. Because of high socioeconomic heterogeneity and chaotic urbanisation, homelessness might play an important role in the TB burden in SPS. Our aim was to determine the association between homelessness and outcome of treatment of pulmonary TB (PTB) in SPS. METHODS: A historical cohort from the routine SPS TB database for 2009-2013 was analysed. The study population was newly diagnosed adult patients with PTB. Homelessness was ascertained at notification or when treatment started. Our outcome was unsuccessful outcome of treatment. We used logistic regression to adjust for potential confounders and multiple imputation for missing data. RESULTS: We analysed 61,817 patients; 1726 (2.8 %, 95%CI 2.7-2.9 %) were homeless. Homeless patients were concentrated in bigger cities, were more frequently middle-aged males, had black/brown skin colour, and had received less education (P < 0.001, for all). Alcohol and drug use was three times more frequent in homeless patients (43.2 % vs 14.4 %, 30.2 % vs. 9.4 %, P < 0.001, respectively). HIV testing was less common among the homeless, of whom 17.3 % were HIV positive compared with 8.5 % among the not homeless population (P < 0.001). Microbiologic confirmation was more frequent among the homeless (91.6 % vs. 84.8 %, P < 0.001). Unsuccessful outcome of treatment was 57.3 % among the homeless and 17.5 % among the not homeless (OR = 6.32, 95%CI 5.73-6.97, P < 0.001), mainly due to loss to follow-up (39 %) and death (10.5 %). After full adjustment for potential confounders, homelessness remained strongly associated with lower treatment success (aOR = 4.96, 95 % CI 4.27-5.76, P < 0.001). HIV status interacted with homelessness: among HIV-infected patients, the aOR was 2.45 (95%CI 1.90-3.16, Pinteraction < 0.001). The population attributable fraction for the joint effect of homelessness, alcohol and drug use was almost 20 %. CONCLUSIONS: Confirming our hypothesis, homelessness led to a marked reduction in the successful treatment of newly diagnosed pulmonary tuberculosis. Homelessness and associated conditions were important contributors to lack of treatment success in pulmonary tuberculosis in Sao Paulo. A multifaceted intervention must be implemented to target this vulnerable population. PMID- 27006010 TI - What Goes Around Comes Around .... PMID- 27006011 TI - Nitric Oxide Deficit Drives Intimal Hyperplasia in Mouse Models of Hypertension. AB - OBJECTIVE: To evaluate the impact of different types of hypertension on the development of intimal hyperplasia (IH). METHOD: Genetic, surgical, and pharmacological models of hypertension were used to compare IH formation in a murine model of carotid artery ligation (CAL). CAL was performed in normotensive WT male mice and in three mouse models of hypertension: (1) L-NAME (Nomega-nitro l-arginine-methyl-ester) treatment for 2 weeks prior to CAL to instate renin independent hypertension; (2) 2K1C (two kidneys, one clip) surgery 1 week prior to CAL to induce renin-dependent hypertension; (3) Cx40-/- mice, a genetic model of renin-dependent hypertension. Mice were sacrificed prior to CAL or 3, 14, or 28 days post CAL. Data collection included tail blood pressure measurements, and morphometric and histological assessment of the ligated carotids. RESULTS: CAL triggered the formation of a VSMC-rich neointima layer after 14-28 days, which was increased in all hypertensive mice. Despite similarly increased blood pressure, L-NAME treated mice displayed more IH than all other hypertensive groups. In addition, L-NAME induced hypertension triggered more cell proliferation and recruitment of CD45 positive inflammatory cells to the ligated vessel wall compared with Cx40-/- or normotensive WT mice. CONCLUSIONS: NO deficiency is a major aspect of vascular inflammation, VSMC proliferation, and IH in hypertensive conditions. PMID- 27006012 TI - US pledges better protection for babies born to addicts. PMID- 27006013 TI - Managing language mismatches in emergency calls. AB - The complex linguistic profile of South Africa has the potential to limit the efficiency of emergency calls. Emergency services depend on rapid resolution of a call, dispatch of an ambulance and response at scene. Resolving language mismatches is a critical feature of everyday practice in such a setting. This study examined accommodation to language shifts in a call centre using conversation analysis methods. Three main call trajectories were identified and the analysis suggested marked differences in responsivity, reflecting attitudinal and societal stratification. Conversation analysis provided insight into communication barriers and contextual features, which have implications for training. PMID- 27006014 TI - Effect of lateral femoral cutaneous nerve-block on pain after total hip arthroplasty: a randomised, blinded, placebo-controlled trial. AB - BACKGROUND: Total hip arthroplasty (THA) is a common procedure associated with moderate postoperative pain. No nerve block without loss of motor function has been documented for THA. We hypothesised that an ultrasound-guided lateral femoral cutaneous nerve (LFCN) block added to a multimodal postoperative pain regimen would reduce postoperative pain after THA. METHODS: One hundred patients who had a THA by the posterior approach were evaluated in this randomised, placebo-controlled, blinded, parallel-group trial comparing an ultrasound-guided LFCN-block with either 8 ml of ropivacaine, 7.5 mg/ml, (Group Ropivacaine) or 8 ml of saline (Group Placebo) given postoperatively. Surgery was performed under spinal anaesthesia. The primary outcome was pain (measured on a Visual Analogue Scale (VAS)) 4 h post-blockade during 30 degrees flexion of the hip. Secondary outcomes were pain at rest, pain during movement, oxycodone consumption (0-24 h), time to mobilisation, ability to mobilise, and length of stay. Patients, assessors and all staff involved with patient care were blinded to the intervention. RESULTS: There was no difference in primary outcome between Group Ropivacaine and Group Placebo (VAS 27 mm vs. 31 mm, p = 0.41; difference -5 mm (95% CI: -15 mm - +5 mm). No differences in any of the secondary outcomes were observed. No adverse events, or harms, were observed during the trial. CONCLUSION: Pain scores, opioid use, time to mobilisation, and length of stay were low in both Group Ropivacaine and Group Placebo. We found no added analgesic effect of a LFCN-block when combined with paracetamol and ibuprofen after THA by the posterior approach. TRIAL REGISTRATION: EudraCT: 2013-004501-12 (December 16th 2013). PMID- 27006015 TI - Ulcerated Plaques on the Groin of an Immunosuppressed Woman. PMID- 27006016 TI - Spontaneous Remission of Recalcitrant Warts in Girls After Human Papillomavirus Vaccination. PMID- 27006017 TI - Kaposi Varicelliform Eruption: A Dermatologic Complication. PMID- 27006018 TI - Pityriasis Rotunda and Hyperprolactinemia. PMID- 27006020 TI - Development and Applications of Portable Gas Chromatography-Mass Spectrometry for Emergency Responders, the Military, and Law-Enforcement Organizations. AB - Portable gas chromatography-mass spectrometry (GC-MS) systems are being deployed for field use, and are designed with this goal in mind. Performance characteristics of instruments that are successful in the field are different from those of equivalent technologies that are successful in a laboratory setting. These field-portable systems are extending the capabilities of the field user, providing investigative leads and confirmatory identifications in real time. Many different types of users benefit from the availability of this technology including emergency responders, the military, and law-enforcement organizations. This manuscript describes performance characteristics that are important for field-portable instruments, especially field-portable GC-MS systems, and demonstrates the value of this equipment to the disciplines of explosives investigations, fire investigations, and counterfeit-drug detection. This paper describes the current state of portable GC-MS technology, including a review of the development of portable GC-MS, as well as a demonstration of the value of this capability using different examples. PMID- 27006019 TI - Development of a Portable Field Imaging Spectrometer: Application for the Identification of Sun-Dried and Sulfur-Fumigated Chinese Herbals. AB - We fabricated a visible-near-infrared (Vis-NIR) portable field imaging spectrometer with a prism-grating-prism element and a scanning mirror. The developed Vis-NIR imaging spectrometer, consisting of an INFINITY 3-1 detector and a V10E spectrometer from Specim Corporation, is designed to measure the spectral range between 0.4 and 1 um with spectral resolution of 2-4 nm. In recent years, sulfur fumigation has been abused during the processing of certain freshly harvested Chinese herbs. Fourier transform infrared spectroscopy, fiber optic NIR spectrometry, and liquid chromatography-mass spectrometry are typically used to analyze the chemical profiles of sulfur-fumigated and sun-dried Chinese herbs. Field imaging spectrometry is rarely used to identify sulfur-fumigated herbs. In this study, field imaging spectrometry, principal component analysis, and the partial least squares-discriminant analysis multivariate data analysis method are used to distinguish sun-dried and sulfur-fumigated Chinese medicinal herbs with a sensitivity of 96.4% and a specificity of 98.3% for RPA identification. These results suggest that hyperspectral imaging is a potential technique to control medicine quality for medical applications. PMID- 27006021 TI - Rapid Analysis of Copper Ore in Pre-Smelter Head Flow Slurry by Portable X-ray Fluorescence. AB - Copper laden ore is often concentrated using flotation. Before the head flow slurry can be smelted, it is important to know the concentration of copper and contaminants. The concentration of copper and other elements fluctuate significantly in the head flow, often requiring modification of the concentrations in the slurry prior to smelting. A rapid, real-time analytical method is needed to support on-site optimization of the smelter feedstock. A portable, handheld X-ray fluorescence spectrometer was utilized to determine the copper concentration in a head flow suspension at the slurry origin. The method requires only seconds and is reliable for copper concentrations of 2.0-25%, typically encountered in such slurries. PMID- 27006022 TI - Automated Fast Screening Method for Cocaine Identification in Seized Drug Samples Using a Portable Fourier Transform Infrared (FT-IR) Instrument. AB - Quick and presumptive identification of seized drug samples without destroying evidence is necessary for law enforcement officials to control the trafficking and abuse of drugs. This work reports an automated screening method to detect the presence of cocaine in seized samples using portable Fourier transform infrared (FT-IR) spectrometers. The method is based on the identification of well-defined characteristic vibrational frequencies related to the functional group of the cocaine molecule and is fully automated through the use of an expert system. Traditionally, analysts look for key functional group bands in the infrared spectra and characterization of the molecules present is dependent on user interpretation. This implies the need for user expertise, especially in samples that likely are mixtures. As such, this approach is biased and also not suitable for non-experts. The method proposed in this work uses the well-established "center of gravity" peak picking mathematical algorithm and combines it with the conditional reporting feature in MicroLab software to provide an automated method that can be successfully employed by users with varied experience levels. The method reports the confidence level of cocaine present only when a certain number of cocaine related peaks are identified by the automated method. Unlike library search and chemometric methods that are dependent on the library database or the training set samples used to build the calibration model, the proposed method is relatively independent of adulterants and diluents present in the seized mixture. This automated method in combination with a portable FT-IR spectrometer provides law enforcement officials, criminal investigators, or forensic experts a quick field-based prescreening capability for the presence of cocaine in seized drug samples. PMID- 27006023 TI - Wireless Data Acquisition of Transient Signals for Mobile Spectrometry Applications. AB - Wireless data acquisition using smartphones or handhelds offers increased mobility, it provides reduced size and weight, it has low electrical power requirements, and (in some cases) it has an ability to access the internet. Thus, it is well suited for mobile spectrometry applications using miniaturized, field portable spectrometers, or detectors for chemical analysis in the field (i.e., on site). There are four main wireless communications standards that can be used for wireless data acquisition, namely ZigBee, Bluetooth, Wi-Fi, and UWB (ultra-wide band). These are briefly reviewed and are evaluated for applicability to data acquisition of transient signals (i.e., time-domain) in the field (i.e., on-site) from a miniaturized, field-portable photomultiplier tube detector and from a photodiode array detector installed in a miniaturized, field-portable fiber optic spectrometer. These are two of the most widely used detectors for optical measurements in the ultraviolet-visible range of the spectrum. A miniaturized, 3D printed, battery-operated microplasma-on-a-chip was used for generation of transient optical emission signals. Elemental analysis from liquid microsamples, a microplasma, and a handheld or a smartphone will be used as examples. Development and potential applicability of wireless data acquisition of transient optical emission signals for taking part of the lab to the sample types of mobile, field-portable spectrometry applications will be discussed. The examples presented are drawn from past and ongoing work in the authors' laboratory. A handheld or a smartphone were used as the mobile computing devices of choice. PMID- 27006024 TI - Stacked, Mutually Rotated Diffraction Gratings as Enablers of Portable Visible Spectrometry. AB - Two-dimensional color CMOS cameras have become ubiquitous. They promise to support ubiquitous spectrometry. When raw illumination levels can be measured by such cameras, their use for spectrometry depends on using as many pixels as possible and on being able to calibrate images at point-of-use. Stacked, mutually rotated transmission diffraction gratings provide a means to generate multi order, wide dynamic range dispersed visible spectra suitable for absorption, reflection, and fluorescence spectrometry. The theoretical basis for dispersion, resolution, and normalization of such spectra are derived, and initial characterization is reported. PMID- 27006025 TI - Analysis of Twenty-Two Performance Properties of Diesel, Gasoline, and Jet Fuels Using a Field-Portable Near-Infrared (NIR) Analyzer. AB - The change in custody of fuel shipments at depots, pipelines, and ports could benefit from an analyzer that could rapidly verify that properties are within specifications. To meet this need, the design requirements for a fuel analyzer based on near-infrared (NIR) spectroscopy, such as spectral region and resolution, were examined. It was found that the 1000 to 1600 nm region, containing the second CH overtone and combination vibrational modes of hydrocarbons, provided the best near-infrared to fuel property correlations when path length was taken into account, whereas 4 cm(-1) resolution provided only a modest improvement compared to 16 cm(-1) resolution when four or more latent variables were used. Based on these results, a field-portable near-infrared fuel analyzer was built that employed an incandescent light source, sample compartment optics to hold 2 mL glass sample vials with ~1 cm path length, a transmission grating, and a 256 channel InGaAs detector that measured the above stated wavelength range with 5-6 nm (~32 cm(-1)) resolution. The analyzer produced high signal-to-noise ratio (SNR) spectra of samples in 5 s. Twenty-two property correlation models were developed for diesel, gasoline, and jet fuels with root mean squared error of correlation - cross-validated values that compared favorably to corresponding ASTM reproducibility values. The standard deviations of predicted properties for repeat measurements at 4, 24, and 38C were often better than ASTM documented repeatability values. The analyzer and diesel property models were tested by measuring seven diesel samples at a local ASTM certification laboratory. The standard deviations between the analyzer determined values and the ASTM measured values for these samples were generally better than the model root mean squared error of correlation-cross-validated values for each property. PMID- 27006026 TI - The relationship between work climate and nurse educators' use of information technology. AB - Understanding organizational behavior and the attitudes of individuals in organizations is crucial for policymakers and managers. Work climate is a major part of these constructs. The main goal of this study was to examine the perceptions of academic nurse educators about their work climate, concerning the use of information technology (IT), including examining a number of variables such as self-efficacy, innovativeness, attitudes, intention to use, and actual use of information technology. METHOD: This study used a quantitative research design, using written and online surveys submitted to 109 academic nurse educators working at ten different academic nursing schools in Israel. RESULTS: The relationship between work climate and actual use of IT was mediated by personality characteristics such as attitude toward using IT, self-efficacy, and innovativeness. Work climate positively predicted both self-efficacy and attitudes toward IT, but did not directly predict innovativeness and did not predict actual use. CONCLUSION: Policymakers and managers should consider work climate and personality characteristics as important factors in their efforts to promote IT use in nursing. As a result, nurse educators would become better acquainted with new technologies, and their acceptance of IT would improve. The organization would benefit from a better work environment and from enhanced performance. PMID- 27006027 TI - Interprofessional undergraduate students talk about nurses and nursing: A qualitative study. AB - OBJECTIVES: To understand the discourse amongst a range of health professional students, including nursing, talking about nurses and nursing. DESIGN: A qualitative descriptive study which employed the use of focus groups. SETTINGS: A rural and residential interprofessional immersion programme in a rural location in New Zealand. The participants were final year undergraduates drawn from seven different degrees (dentistry, dietetics, medicine, nursing, occupational therapy, pharmacy and physiotherapy). METHODS: Data were collected from separate and sequential group interviews; each of which comprised a different mix of students and always included nursing students. Each student participated once. Data were analysed by comparing datum with datum until recurrent themes emerged. RESULTS: The discourse in relation to nurses and nursing identified two overarching themes 'constrained conversations' and 'the benefit of IPE: what nursing might become'. Within those themes there were four contributing sub themes; 'nursing as doing', 'limiting our vocabulary', 'becoming part of the conversation 'and 'moving from the present to the future what nursing might become'. CONCLUSIONS: The interprofessional experience for student nurses not only enabled them to learn about other professions but was a forum in which they were able to articulate the role of the nurse. This was an unintended and positive by-product of the IPE programme. PMID- 27006028 TI - Exploring the compassion deficit debate. AB - Several recent high profile failures in the UK health care system have promoted strong debate on compassion and care in nursing. A number of papers articulating a range of positions within this debate have been published in this journal over the past two and a half years. These articulate a diverse range of theoretical perspectives and have been drawn together here in an attempt to bring some coherence to the debate and provide an overview of the key arguments and positions taken by those involved. In doing this we invite the reader to consider their own position in relation to the issues raised and to consider the impact of this for their own practice. Finally the paper offers some sense of how individual practitioners might use their understanding of the debates to ensure delivery of good nursing care. PMID- 27006029 TI - Nursing students' perception of high-fidelity simulation activity instead of clinical placement: A qualitative study. AB - BACKGROUND: The high-fidelity simulation (HFS) has been utilized in nursing education for more than 20 years. Advantages of the use of high-fidelity simulation in nursing education have been documented in the literature. Based on the advantages, it has been arranged as a part of the clinical study course of the first year baccalaureate nursing program in one of the nursing colleges in Macau recently. OBJECTIVE: The aim of this study is to explore undergraduate nursing students' perception of using high-fidelity simulation as part of their clinical study course in Macau. DESIGN: This is a qualitative study using open ended questionnaire. SETTING: This study was implemented at the nursing laboratory between 1 April and 17 April 2015, which was the period of preliminary clinical study course of year one nursing students. PARTICIPANTS: A purposive sample was sought from the voluntary year one undergraduate nursing students who participated in the clinical study course. METHODS: Students received two high fidelity simulation sections during the course, while a self-administered open ended questionnaire was allocated afterward. Qualitative content analysis was performed after data collection. RESULTS: Two themes emerged in this study, which included "appreciation" and "misunderstanding". They were further divided into five categories; as "positive feelings", "gaining a suitable atmosphere for learning", "assist of adequate emergency preparation: resourceful ability", "contempt", and "rote learning". CONCLUSION: This was the first time to utilize HFS activities as a part of the clinical study course in one nursing college in Macau. These HFS activities instead of a part of real clinical placement were appreciated by nursing students. And it mainly contributed to the resourceful ability in students' view. During the HFS activities, nursing educators should consider the misunderstanding of HFS activities of students that a few nursing students despised simulator's life and got rote learning method. PMID- 27006030 TI - The corporate construction of psychosis and the rise of the psychosocial paradigm: Emerging implications for mental health nurse education. PMID- 27006031 TI - Retention and academic performance of undergraduate nursing students with advanced standing: A mixed-methods study. AB - BACKGROUND: Undergraduate nursing students enter university through a variety of pathways. For some students, this includes the granting of advanced standing based on recognition of prior qualifications. The impact of advanced standing on nursing students' transition, retention and success at university is not well understood. OBJECTIVES: The aim of this study was to examine the retention, academic success and experiences of students who commenced their undergraduate nursing studies with advanced standing. DESIGN, SETTING, PARTICIPANTS AND METHODS: A sequential exploratory mixed-methods design was used in this study, which involved undergraduate nursing students enrolled at a multi-campus university in Australia. Nursing students who enrolled in 2014 and did not opt out of program level research were included in the study. RESULTS: Students with advanced standing were older (mean 31.6 versus 25.8 years, p<0.001) and more likely to discontinue their studies at the end of semester one (97% versus 95%, p=0.015) than standard-entry students. Advanced standing was also shown to be an independent predictor of low GPA [OR: 1.69 (95% CI: 1.06 to 2.69]. Most students with advanced standing commenced directly into second year (45%) missing first year student connections and programs. Students reported feeling apprehensive, forgotten and ill-prepared for the expectations of university. Some showed significant strength and resilience while others were struggling to cope with the workload with minimal knowledge or understanding of supports available to them. CONCLUSIONS: The widening participation agenda is a commendable strategy; however, students who enter university with advanced standing need targeted support to promote their transition, retention and success at university. PMID- 27006032 TI - Diabetes knowledge of nurses in different countries: An integrative review. AB - OBJECTIVE: The aim of this study was to identify, critically appraise and synthesise evidence of nurses' knowledge of diabetes and identify factors that function as barriers to nurses' acquisition of diabetes knowledge. DESIGN: An integrative review METHODS: A systematic search was conducted for English language, peer reviewed publications of any research design via CINAHL, Medline, EMBASE, and Education Research Complete databases from 2004 to 2014. Of 374 articles retrieved, after removal of duplicates and quality appraisal, 25 studies were included in the review and synthesised based on study characteristics, design and findings. FINDINGS: Studies originated from developed and developing countries and applied a variety of research designs and tools to assess nurses' knowledge of diabetes. Assessed aspects of diabetes care included knowledge of diabetes medications (12 studies), nutrition (7), blood glucose monitoring (7), diabetes complications (6), and pathology, symptoms and diabetes management (9). Factors/barriers affecting nurses' acquisition of diabetes knowledge were identified (11). Overall, findings indicated wide-spread serious and sustained deficiencies in nurses' knowledge of diabetes and diabetes care. CONCLUSION: With nurses demonstrating significant and long-standing knowledge deficits in many aspects of diabetes care, strategies are urgently required to overcome the identified barriers to knowledge acquisition. PMID- 27006033 TI - Competencies required for nursing telehealth activities: A Delphi-study. AB - BACKGROUND: Telehealth is viewed as a major strategy to address the increasing demand for care and a shrinking care professional population. However, most nurses are not trained or are insufficiently trained to use these technologies effectively. Therefore, the potential of telehealth fails to reach full utilization. A better understanding of nursing telehealth entrustable professional activities (NT-EPAs) and the required competencies can contribute to the development of nursing telehealth education. METHOD: In a four-round Delphi study, a panel of experts discussed which NT-EPAs are relevant for nurses and which competencies nurses need to possess to execute these activities effectively. The 51 experts, including nurses, nursing faculty, clients and technicians all familiar with telehealth, were asked to select items from a list of 52 competencies based on the literature and on a previous study. Additionally, the panelists could add competencies based on their experience in practice. The threshold used for consensus was set at 80%. RESULTS: Consensus was achieved on the importance of fourteen NT-EPAs, requiring one or more of the following core competencies; coaching skills, the ability to combine clinical experience with telehealth, communication skills, clinical knowledge, ethical awareness, and a supportive attitude. Each NT-EPA requires a specific set of competencies (at least ten). In total, 52 competencies were identified as essential in telehealth. DISCUSSION/CONCLUSION: Many competencies for telehealth, including clinical knowledge and communication skills, are not novel competencies. They are fundamental to nursing care as a whole and therefore are also indispensable for telehealth. Additionally, the fourteen NT-EPAs appeared to require additional subject specific competencies, such as the ability to put patients at ease when they feel insecure about using technology. The NT-EPAs and related competencies presented in this study can be used by nursing schools that are considering including or expanding telehealth education in their curriculum. PMID- 27006034 TI - Should I stay or should I go? A systematic review of factors that influence healthcare students' decisions around study abroad programmes. AB - BACKGROUND: Study abroad programmes have been shown to have significant benefits for participating healthcare students such as promoting cultural awareness and understanding of different healthcare settings, policies and practices. Healthcare students are encouraged to undertake elective or Erasmus placements overseas to enhance personal and professional development and to broaden horizons through lived cultural experience. However, there is a relatively low uptake of such opportunities amongst this student group. OBJECTIVES: This systematic review aimed to explore factors that influence healthcare students' decision making around study abroad opportunities within undergraduate training programmes. REVIEW DESIGN METHODS: A systematic review was undertaken utilising a narrative synthesis approach. DATA SOURCES: A comprehensive literature search was conducted on MEDLINE, CINAHL, EMBASE, PsycINFO, ASSIA, and ERIC databases. Key institutions were contacted for grey literature. Studies that reported on factors that influence healthcare students' decisions regarding study abroad programmes were included in the review. RESULTS: Ten studies were identified for inclusion (5 qualitative studies, 5 surveys), indicating a paucity of research in this area. Data synthesis indicates that factors that influence healthcare students' decisions to participate in study abroad programmes are similar across different geographic locations and different professional groups. Factors that support decisions to study overseas include having sufficient information about study abroad programmes, especially early in an academic programme, having an interest in other cultures/countries and having academic staff and family as positive role models who motivate them to study abroad. Key barriers are cost and language issues. Language remains a significant barrier even when generous bursaries are available, as with the Erasmus scheme, when students are not proficient with the language spoken in host countries. Students tend to prefer destinations where language is not a problem or where countries have cultural or historical connections, such as being part of the Commonwealth countries. CONCLUSIONS: Promotion of study abroad opportunities needs to start early in an academic programme. It should include detailed information and provision of language support. Faculty have an important part to play as enthusiastic role models. PMID- 27006035 TI - The effect of nurse education on the self-esteem and assertiveness of nursing students: A four-year longitudinal study. AB - BACKGROUND: The nurse education program affects many aspects of personal development. Nursing students gain skills in critical thinking and analysis and also develop communication and management skills. The four-year program may also have an effect on students' assertiveness and self-esteem. OBJECTIVES: This study was conducted to determine the impact of the four-year higher nursing school educational program on students' self-esteem and assertiveness. DESIGN: Descriptive longitudinal design. SETTING: The study took place at a Foundation University in Istanbul, Turkey over the period 2006-2010. The students' levels of self-esteem and assertiveness were assessed at the beginning and end of the first, second, third and fourth years of the program. PMID- 27006036 TI - Failing securely: The processes and support which underpin English nurse mentors' assessment decisions regarding under-performing students. AB - BACKGROUND: This study was undertaken in response to concerns that mentors who assessed practical competence were reluctant to fail student nurses which generated doubts about the fitness to practise of some registered nurses. Limited evidence was available about the experiences of mentors who had failed underperforming students and what had helped them to do this. AIM: To investigate what enabled some mentors to fail underperforming students when it was recognised that many were hesitant to do so. METHOD: An ethically approved, grounded theory approach was used to explore thirty-one nurses' experiences of failing student nurses in practical assessments in England. Participants were recruited using theoretical sampling techniques. Semi-structured interviews were conducted. Analysis was undertaken using iterative, constant comparative techniques and reflexive processes. The theoretical framework which emerged had strong resonance with professionals. FINDINGS: Five categories emerged from the findings: (1) Braving the assessment vortex; (2) Identifying the 'gist' of underperformance; (3) Tempering Reproach; (4) Standing up to scrutiny; and (5) Drawing on an interpersonal network. These categories together revealed that mentors needed to feel secure to fail a student nurse in a practical assessment and that they used a three stage decision making process to ascertain if this was the case. Many of the components which helped mentors to feel secure were informal in nature and functioned on goodwill and local arrangements rather than on timely, formal, organisational systems. The mentor's partner/spouse and practice education facilitator or link lecturer were identified as the key people who provided essential emotional support during this challenging experience. CONCLUSION: This study contributes to understanding of the combined supportive elements required for robust practical assessment. It presents a new explanatory framework about how mentors formulate the decision to fail a student nurse and the supportive structures which are necessary for this to occur. PMID- 27006037 TI - The effect of an enrolled nursing registration pathway program on undergraduate nursing students' confidence level: A pre- and post-test study. AB - BACKGROUND: In the latter half of the 20th century, registered nurse education moved to university degree level. As a result, there has been a reduction in access for students to clinical experience. In numerous studies, nursing graduates have reported that they do not feel prepared for practice. The importance of maximising every learning opportunity during nursing school is paramount. At Edith Cowan University, a program was initiated that allows students to become enrolled nurses at the midway point of their degree to enable them to work and therefore gain experience in the clinical practice setting during their education. This study investigated the effect of the program on the nursing students' perception of their clinical abilities and explored their ability to link theory to practice. METHODS: The research design for this study was a quasi-experimental, prospective observational cohort study. The study included 39 second-year nursing students not enrolled in the program (Group 1), 45 second-year nursing students enrolled in the program (Group 2), and 28 third year nursing students who completed the program and are working as enrolled nurses (Group 3). Participants were asked to complete a Five Dimension of Nursing Scale questionnaire. RESULTS: The quantitative analyses showed that students in Group 1 had statistically significant higher pre-questionnaire perceived abilities across all domains, except in two dimensions when compared to Group 2. The post-questionnaire analysis showed that Group 1 had statistically significant lower perceived abilities in four of the five dimensions compared to Group 2. Group 1 also had significantly lower abilities in all dimensions compared to Group 3. Group 3 had a significantly higher perception of their clinical abilities compared to Group 2. CONCLUSION: This study highlights the value of meaningful employment for undergraduate nursing students by providing opportunities to increase confidence in clinical abilities. PMID- 27006038 TI - The effects of pediatric community simulation experience on the self-confidence and satisfaction of baccalaureate nursing students: A quasi-experimental study. AB - OBJECTIVES: Simulation in nursing education is a means to transform student learning and respond to decreasing clinical site availability. This study proposed an innovative simulation experience where students completed community based clinical hours with simulation scenarios. The purpose of this study was to determine the effects of a pediatric community simulation experience on the self confidence of nursing students. Bandura's (1977) Self-Efficacy Theory and Jeffries' (2005) Nursing Education Simulation Framework were used. DESIGN: This quasi-experimental study collected data using a pre-test and posttest tool. The setting was a private, liberal arts college in the Midwestern United States. PARTICIPANTS: Fifty-four baccalaureate nursing students in a convenience sample were the population of interest. The sample was predominantly female with very little exposure to simulation prior to this study. METHODS: The participants completed a 16-item self-confidence instrument developed for this study which measured students' self-confidence in pediatric community nursing knowledge, skill, communication, and documentation. RESULTS: The overall study showed statistically significant results (t=20.70, p<0.001) and statistically significant results within each of the eight 4-item sub-scales (p<0.001). Students also reported a high level of satisfaction with their simulation experience. CONCLUSIONS: The data demonstrate that students who took the Pediatric Community Based Simulation course reported higher self-confidence after the course than before the course. Higher self-confidence scores for simulation participants have been shown to increase quality of care for patients. PMID- 27006039 TI - An exploratory qualitative analysis of student midwives views of teaching methods that could build their confidence to deliver perinatal bereavement care. AB - BACKGROUND: Equipping student midwives with confidence to deliver bereavement care to childbearing women is a challenge for midwifery lecturers. OBJECTIVE: To explore qualitative data provided by student midwives who evaluated the workbook Bereavement care for childbearing women and their families (Hollins Martin & Forrest, 2013) to explore their views of potential teaching strategies that could build their confidence to deliver real bereavement care. METHOD: An exploratory qualitative thematic analysis was used to provide, analyse and report themes identified within data collected in a prior study. PARTICIPANTS: Participants were student midwives (n=179) in their second/third year of a midwifery degree program at 1 of 3 universities in the UK were included in the study. DATA COLLECTION/ANALYSIS: Data to evaluate effectiveness of the bereavement workbook as a teaching method was collected using a survey instrument. It was the comments written under questions by participants that were analysed in the present study. FINDINGS: Three themes emerged: (1) increasing classroom interaction, (2) the importance of reflecting on emotions, and (3) need for experience. DISCUSSION: Although this study has addressed delivery of education that relates to midwives, the findings are cross transferable to other healthcare educators, practitioners, and students. Several solutions are proposed that could potentially build student confidence to deliver bereavement care: lecturers should (1) encourage group discussion in the classroom to help build student confidence to emotionally cope during real bereavement events; (2) ensure students gain exposure by encouraging qualified midwives to include them in real bereavement events early on in their training, and (3) develop packages of perinatal bereavement scenarios for simulation and rehearsal in the clinical skills laboratory. Post-implementation, it is recommended that these teaching strategies be evaluated. PMID- 27006040 TI - A new strategy in nursing education: From hybrid simulation to clinical practice. AB - BACKGROUND: Various instructional environments are used in nurse education to develop students' psychomotor and communication skills, reduce their anxiety levels, and enhance their satisfaction. OBJECTIVES: To examine the effect of three different instructional environments on the development of the students' psychomotor and communication skills and their levels of anxiety and satisfaction. DESIGN: A prospective study design was used. METHODS: The study sample consisted of 60 nursing students. Before the implementation of the study, the students' cognitive skills and trait anxiety levels were evaluated. The students were divided into five groups and five nursing activities (Leopold's maneuvers, teaching breastfeeding, family planning education, teaching vulvar self-examination and teaching breast self-examination) were specified for each group. They implemented these nursing activities under the supervision of a faculty member in the nursing skills laboratory (NSL), standardized patient laboratory (SPL) and clinical practice environment (CPE) respectively. In each instructional environment, the students' psychomotor and communication skills, state anxiety levels and satisfactions were evaluated. RESULTS: The median scores for psychomotor skills [NSL=73.1;SPL=81.5;CPE=88.6] and communication skills [NSL=64.9;SPL=71.6;CPE=79.0] were found to increase as the students went on practicing in a more complicated environment (p<0.05). Similarly, it was determined that the students' anxiety levels decreased as they were practicing incrementally [NSL=33.0;SPL=32.0;CPE=31.0]. As the instructional environments were getting more similar to the reality, the students' satisfaction levels were found to become higher. CONCLUSIONS: Students who deliberately practice in the instructional environments until they are competent develop their psychomotor skills while reducing their anxiety levels, and enhancing their communication skills and satisfaction. For that reason, the development of students' competency areas is thought to be effective for enhancement of patients and health care workers' safety. PMID- 27006041 TI - Clinical Education In psychiatric mental health nursing: Overcoming current challenges. AB - BACKGROUND: In response to current challenges in psychiatric mental health nursing education, nursing schools have implemented new strategies in teaching undergraduate nursing students. OBJECTIVES: The objectives of the study were to evaluate learning outcomes of a mental health nursing clinical practicum and to explore students' perceptions of the clinical practicum. DESIGN: This was a mixed method study. Sixty-three undergraduate nursing students, who were undertaking their first mental health clinical practicum, completed a set of structured questionnaires and answered open-ended questions about the clinical practicum. METHODS: Answers to open-ended questions were analyzed qualitatively, and learning outcomes (i.e., empathy, mental illness prejudice, simulation-related efficacy, and satisfaction) were measured at three time points: pre-clinical, post-simulation, and post-clinical. RESULTS: Students reported improvement in empathy and simulation-related self-efficacy after the clinical practicum, but no change was found in mental illness prejudice. Students' expectations for and evaluation of the clinical practicum are summarized. CONCLUSIONS: The observed improvement in learning outcomes of the clinical practicum may be attributed to the unique contribution of each component of the clinical practicum and the synergic effect of these diverse components. To manage emerging challenges in clinical settings and nursing education, it is critical to develop systematic and comprehensive mental health nursing clinical practicums for undergraduate nursing students. PMID- 27006042 TI - Piloting the feasibility of head-mounted video technology to augment student feedback during simulated clinical decision-making: An observational design pilot study. AB - BACKGROUND: Clinical decision-making is a complex activity that is critical to patient safety. Simulation, augmented by feedback, affords learners the opportunity to learn critical clinical decision-making skills. More detailed feedback following simulation exercises has the potential to further enhance student learning, particularly in relation to developing improved clinical decision-making skills. OBJECTIVE: To investigate the feasibility of head-mounted video camera recordings, to augment feedback, following acute patient deterioration simulations. DESIGN: Pilot study using an observational design. METHODS: Ten final-year nursing students participated in three simulation exercises, each focussed on detection and management of patient deterioration. Two observers collected behavioural data using an adapted version of Gaba's Clinical Simulation Tool, to provide verbal feedback to each participant, following each simulation exercise. Participants wore a head-mounted video camera during the second simulation exercise only. Video recordings were replayed to participants to augment feedback, following the second simulation exercise. Data were collected on: participant performance (observed and perceived); participant perceptions of feedback methods; and head-mounted video camera recording feasibility and capability for detailed audio-visual feedback. RESULTS: Management of patient deterioration improved for six participants (60%). Increased perceptions of confidence (70%) and competence (80%), were reported by the majority of participants. Few participants (20%) agreed that the video recording specifically enhanced their learning. The visual field of the head mounted video camera was not always synchronised with the participant's field of vision, thus affecting the usefulness of some recordings. CONCLUSION: The usefulness of the video recordings, to enhance verbal feedback to participants on detection and management of simulated patient deterioration, was inconclusive. Modification of the video camera glasses, to improve visual-field synchronisation with participants' actual visual field, is recommended to further explore this technology for enhancing student performance. PMID- 27006043 TI - The Capabilities of Nurse Educators (CONE) questionnaire: Development and evaluation. AB - BACKGROUND: To inspire excellent clinicians to become educators, the role of the nurse educator needs to be more fully defined. Capabilities rather than competencies may better describe advanced professional practice. OBJECTIVES: To develop an effective measure of the multifaceted complexity of the nurse educator role, which will enable nurse educators to (1) self-assess their capability set, (2) identify areas for professional development, and (3) evaluate professional development interventions. METHOD: A questionnaire (with 6 subsets) interrogating nurse educator capabilities was developed through wide professional consultation and an expert working group, and evaluated. Statistical analyses investigated internal consistency, internal correlation of items, relationship to professional practice data (also collected via questionnaire), and test-retest reliability of the questionnaire and subsets. PARTICIPANTS: Nurse educators (266) working within universities and health services in Australia and New Zealand. RESULTS: Analyses resulted in a 93-item Capabilities of Nurse Educators (CONE) questionnaire, with six subsets measuring Teaching Knowledge and Practice, Drawing from Nursing Knowledge, Teaching Relationships, Leadership, Research Orientation and Research Action. The questionnaire and subsets demonstrated internal validity (Cronbach's alpha >= .9). Reliability in this population was supported via significant differences between ranked questionnaire scores in ordinal categories of data collected about professional practice. The 8-week test-retest analysis supported the reliability of the CONE over time and suggested the questionnaire could be useful to evaluate the success of professional development activities. CONCLUSIONS: The CONE questionnaire proved useful for measuring the complex capabilities of nurse educators in the academic and health service contexts studied and may assist educators to self-assess their capability sets and identify areas for professional development. It also shows promise as an evaluation tool for professional development. The utility of CONE as a self diagnostic tool in career advancement, particularly in novice educators and educators outside Australia, requires further confirmation. PMID- 27006044 TI - "Clinical simulation as a learning tool in undergraduate nursing: Validation of a questionnaire". AB - BACKGROUND: Clinical simulation allows both students and professionals to perform their clinical practice in a safe environment, facilitating the standardization of contents and promoting the integration of theoretical knowledge into the clinical practice. OBJECTIVES: To design and validate in Spanish the Satisfaction Scale Questionnaire with High-Fidelity Clinical Simulation, instrument created to assess the nursing students' satisfaction with the use of clinical simulation in training. METHODS: The scale items were developed from a review of the literature. Content validity was established by an expert panel. This questionnaire was validated by 150 nursing students in the second year of the Bachelor Degree in Nursing at a Spanish university during the academic year 2013/2015. Lawshe formula was used to determine its validity, while for the construct validity a factor analysis was conducted using the principal component and Varimax rotation. Cronbach Alpha was used to determine internal consistency. RESULTS: The questionnaire developed presents satisfactory internal consistency (alpha 0.857). The factorial analysis indicated a structure of eight principal components that explain the 62.85% of the total variance explained, and in turn each subscale presented acceptable internal consistency. Frequency analysis results show a satisfaction degree higher than 80%, emphasizing "the realism of the cases" (98.7%), that "many benefits are obtained as clinical simulation relates theory to practice" (98.7%), "priorities are established "(97.4%)," errors are corrected after debriefing" (93.4%), and "communication and teamwork improved" (90%). CONCLUSIONS: The scale designed and validated on high-fidelity clinical simulation in the Spanish population is satisfactory and adequate. Nursing students at the University of Cantabria (Spain) reported a high satisfaction degree with clinical simulation, confirming its usefulness in the teaching-learning process. PMID- 27006045 TI - The meaning of being a nurse educator and nurse educators' attraction to academia: A phenomenological study. AB - BACKGROUND: The nursing faculty shortage affects the number of nurse graduates. Understanding the meaning of being a nurse educator and what attracts nurses with graduate degrees to academia, are important considerations in addressing the recruitment and retention of faculty. AIM: The aim of this study was to explore the meaning of being a nurse educator and how nurse educators' understand their attraction to academia. DESIGN AND PARTICIPANTS: The sample population included 15 nurse educators with a master's or doctoral degree, currently teaching in an undergraduate or graduate nursing program in a western Canadian city. METHOD: Data were collected through 15 face-to-face semi-structured interviews using an interview guide. FINDINGS: The meaning of being a nurse educator and how nurse educators understand their attraction to academia illustrates, from the perspective of the participants, how they give meaning to being a nurse educator and how they understand their attraction to academia. Six subthemes emerged: (1) opportunities, (2) wanting to teach, (3) seeing students learn, (4) contributing to the profession, (5) the unattractive, and (6) flexibility. CONCLUSION: The faculty shortage is a complex issue, one that will persist into the foreseeable future. Understanding how nurse educators experience academia and how the meaning of these experiences attract them to academia, will facilitate the development of creative strategies to recruit and retain qualified nurse educators. PMID- 27006046 TI - Graduating nurses' self-efficacy in palliative care practice: An exploratory study. AB - BACKGROUND: Educational institutions and the health care industry agree that graduates from professional programs need to be "work ready" and capable of delivering competent and confident nursing care. One measure of program success is the student's self-efficacy in meeting expected graduate capabilities. In this study student's self-efficacy is related to palliative care graduate capabilities. AIM: To explore graduating Bachelor of Nursing Science (BNSc) students' self-efficacy in caring for palliative care patients. DESIGN: A qualitative design using semi-structured face-to-face interviews. SETTING: A regional Australian university. PARTICIPANTS: A purposive sample of 10 students in their final semester of study in a Bachelor of Nursing Science degree program. METHOD: Semi-structured face-to-face interviews were conducted. Interview questions were informed by published palliative care graduate capabilities. Interview data were transcribed verbatim and coded by capability. The coded data were then analysed to determine evidence of self-efficacy in caring for palliative care patients. RESULTS: All participants had experiences in caring for palliative care patients. However, the responses did not consistently reflect high degrees of self-efficacy in four documented palliative care graduate capabilities required to care for persons with a life-limiting illness. CONCLUSIONS: The findings support others that have identified gaps between curriculum and health care industry requirements in terms of students' beliefs about their empowerment to deliver nursing care as graduates. Education interventions and approaches to program evaluation require further development to better support students' growth of self-efficacy in undertaking their graduate roles. PMID- 27006047 TI - Selection of nursing teaching strategies in mainland China: A questionnaire survey. AB - BACKGROUND: In nursing education, the traditional lecture and direct demonstration teaching method cannot cultivate the various skills that nursing students need. How to choose a more scientific and rational teaching method is a common concern for nursing educators worldwide. OBJECTIVE: To investigate the basis for selecting teaching methods among nursing teachers in mainland China, the factors affecting the selection of different teaching methods, and the application of different teaching methods in theoretical and skill-based nursing courses. DESIGN: Questionnaire survey. SETTINGS: Seventy one nursing colleges from 28 provincial-level administrative regions in mainland China. PARTICIPANTS: Following the principle of voluntary informed consent, 262 nursing teachers were randomly selected through a nursing education network platform and a conference platform. METHODS: The questionnaire contents included the basis for and the factors influencing the selection of nursing teaching methods, the participants' common teaching methods, and the teaching experience of the surveyed nursing teachers. The questionnaires were distributed through the network or conference platform, and the data were analyzed by SPSS 17.0 software. RESULTS: The surveyed nursing teachers selected teaching methods mainly based on the characteristics of the teaching content, the characteristics of the students, and their previous teaching experiences. The factors affecting the selection of teaching methods mainly included large class sizes, limited class time, and limited examination formats. The surveyed nursing teachers primarily used lectures to teach theory courses and the direct demonstration method to teach skills courses, and the application frequencies of these two teaching methods were significantly higher than those of other teaching methods (P=0.000). CONCLUSION: More attention should be paid to the selection of nursing teaching methods. Every teacher should strategically choose teaching methods before each lesson, and nursing education training focused on selecting effective teaching methods should be more extensive. PMID- 27006048 TI - Connecting learners online: Challenges and issues for nurse education--Is there a way forward? AB - Nurse educators face many challenges due to what has undoubtedly been an era of massive change and innovation. Technological advances in the fields of communication, social media, and education generally have afforded new ways of connecting and working with students. In particular, the development of large scale learning management systems has changed the face of higher education. Such technological innovations have inadvertently placed pressure on nurse educators to adopt online educational strategies that are not only pedagogically sound but also creative. At the same time, as this technological innovation has occurred, a corresponding emphasis on course design and curriculum renewal has emerged in the sector, calling for the embodiment of the principles of constructive alignment and engaged learning (Brill and Park, 2008; Bonk and Khoo, 2014). As a result, educators grapple to present courses that are grounded in educational theory, align with higher education standards, and provide appropriate activities to support student learning. However, despite access to theoretical and technological support, for the majority of educators, achieving such expectations can be overwhelming and downright frustrating. Revere and Kovach (2011) have noted that the pace of change is often so fast that educators often do not have the time to identify and integrate such changes into their subject design. As a result, there is a tendency for information to become content and resource driven rather than based around more engaging approaches. Simply put, for those nurse educators who are, metaphorically speaking, in the trenches and time poor, what is needed are practical guidelines that focus on sharing information on how to apply online teaching technologies that creatively engage students in the learning process. PMID- 27006049 TI - Student peer reviewers' views on teaching innovations and imaginative learning. AB - BACKGROUND: Various teaching innovations have been proven effective in promoting students' critical thinking, creativity, problem solving and active learning. However, little attention has been paid to the possibility of including students as peer reviewers to evaluate these innovations in light of imaginative learning. AIM: This study explored the perspective of senior students who played the role of the student peer reviewer on three teaching innovations, namely writing poetry, composing songs and creating role-plays in problem-based learning (PBL), specifically in relation to imaginative learning. DESIGN: A focus group interview. METHODS: Ten senior nursing students who had experienced the conventional PBL approach but not the mentioned teaching innovations were invited to participate in reviewing a video recording of a PBL class using the above teaching innovations with a total of 18 junior year students. RESULTS: Five themes were identified using content analysis: (i) motivation to learn, (ii) increased empathy, (iii) information retention, (iv) development of critical thinking and creativity, and (v) drawbacks of teaching innovations. CONCLUSIONS: It is suggested that student peer reviewers should be considered, as they can bring an outsider-learner's views on understanding the impacts of teaching innovations on imaginative learning. A call should be made to invite student peer reviewers on teaching and learning approaches, and more effort should be devoted to promoting an understanding of how imaginative learning can be achieved via teaching innovations. PMID- 27006050 TI - Applying Wenger's communities of practice theory to placement learning. PMID- 27006051 TI - Exploring The effects Of An online asynchronous mindfulness meditation intervention with nursing students On Stress, mood, And Cognition: A descriptive study. AB - BACKGROUND: Nurses returning to school while working, raising families, and maintaining other roles, can experience stress, mood changes and cognition disturbance that negatively impact their academic success. OBJECTIVES: To explore the effect of an online mindfulness meditation intervention with distance nursing students on stress, mood and cognition. DESIGN: A 24 week descriptive study. SETTINGS: An 8 week online intervention was offered to all undergraduate and graduate nursing students, of three nursing programs of a middle-sized university in mid-Atlantic US. PARTICIPANTS: A total of 26 nursing students completed the study. METHODS: An 8 week online, asynchronous mindfulness intervention was provided through the learning management system with a 16 week follow-up. OUTCOMES MEASURES: Perceived Stress Scale (PSS), Hospital Anxiety and Depression Scale (HADS), and Attention Network Test (ANT). RESULTS: Stress was significantly reduced (F(2,24)=4.163, p=.019). A decreasing trend for anxiety was noted with significant difference between time points (F(1,23)=6.889, p=.015) when practice frequency was weekly to daily. Cognition: ability to shift attention, attention selection, concentration, and accuracy improved. CONCLUSION: Findings from this study may illuminate the usefulness of a mindfulness based stress reduction program offered to distance nursing students. Further studies are needed to better demonstrate the effectiveness of the intervention. PMID- 27006052 TI - Anxiety and categorisation effects in student nurses' attitudes towards young and older patients: A dual pathway model. AB - BACKGROUND: Student nurses often have a negative attitude towards older patients due to negative stereotypes, which may explain their reluctance to work in geriatric care. OBJECTIVES: The aim of this study was to investigate a dual effect (direct and indirect via anxiety) of patients' age on student nurses' attitudes towards their patients. DESIGN: Quantitative survey study with 2 between-subjects conditions (patient age: young patients vs. older patients; both n's=52). SETTING: Two schools for higher vocational education in the Netherlands. PARTICIPANTS: 104 student nurses between the ages of 16-30 in the third or fourth year of their nursing education (Mage=21.58, SD=2.22; 93 women). RESULTS: Attitudes towards older patients were more negative than those towards young patients. Older patients also elicited less anxiety compared to young patients, and anxiety had a weaker relationship with attitudes towards older patients than attitudes towards younger patients. Attitudes towards younger patients, but not towards older patients, were depressed by anxiety. CONCLUSIONS: Older patients generate more negative attitudes among student nurses, but can also improve attitudes indirectly by lowering intergroup anxiety. Older people may be therefore be especially suitable as a patient group to receive care from young nurses in training, who can mature in their profession without being anxious over making a wrong impression. PMID- 27006053 TI - The effect of a career activity on the students' perception of the nursing profession and their career plan: A single-group experimental study. AB - BACKGROUND: Students' conceptualizations of nursing and their reasons for choosing the profession motivate them and affect their education, work performance and career plans. Nursing educators should support them to plan their careers consciously during their education. OBJECTIVES: The study aimed to investigate the effect of career-planning event for nursing students on their conceptualizations of the nursing profession and their career plans. DESIGN: The study was as single-group experimental study using a pre-test and post-test. SETTINGS: The career-planning event was held in the conference hall of the university involved in the current study, and was open to the all students of the nursing school. PARTICIPANTS: The sample of the study consisted of 105 students who participated in the "Nursing Career Symposium" held on 27 March 2015. Methods At the event, the importance of career planning and the opportunities of the nursing profession was presented. The data were collected using a questionnaire consisted of two sections including descriptive characteristics and the opinions of the students regarding their career plans and Perception of Nursing Profession Scale. The students completed the first section of the questionnaire before the career event began and the second section of the questionnaire and scale both before and after the event. RESULTS: The participants had positive conceptualizations of the profession. Following a career event, the participants' opinions of professional qualities and professional status as measured through the Perception of Nursing Profession Scale showed a significant increase, and that the event had made an important contribution to their career plans. CONCLUSIONS: In the light of these results, it is possible to suggest that such events have an important place during education in that they introduce the nursing profession, and they develop the students' positive thoughts regarding the profession in terms of both course content and teaching methodology. PMID- 27006054 TI - Nepalese undergraduate nursing students' perceptions of the clinical learning environment, supervision and nurse teachers: A questionnaire survey. AB - BACKGROUND: Clinical practice enables nursing students to acquire essential professional skills, but little is known about nursing students' perceptions of the clinical learning environment (CLE) in Nepal. OBJECTIVES: To examine Nepalese nursing students' perceptions regarding the CLE and supervision. DESIGN: A cross sectional questionnaire design was used. SETTINGS: Government and private hospitals in Nepal where the undergraduate nursing college students undertook their clinical practice. PARTICIPANTS: Students with clinical practice experience were recruited from years 2-4 of the B.Sc. nursing program in Nepal (n=350). The final sample comprised 263 students. METHODS: A self-administered questionnaire including demographic characteristics, latest clinical practice site, and general satisfaction was administered February-March 2014. The previously validated Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale was used in the questionnaire. The analytical approach used exploratory factor analysis, assessments of the scale and sub-dimension reliability, correlations of factors between scale sub-dimensions, and multiple regression analysis. RESULTS: Students' practicum satisfaction level at government hospitals was significantly higher than those at private hospitals (p<0.0001). Five factors explained 85.7% of the variance, with minor factorial structure differences compared with the original scale. Reliability was confirmed (Cronbach's alpha=0.93 for total scale, 0.76-0.92 for sub-dimensions). Inter-correlations between the five original sub dimensions were 0.27-0.68 (p<0.0001). Students undertaking their practicum in private hospitals evaluated their clinical placements significantly more negatively on most sub-dimensions than those in government hospitals. Multiple regression analysis revealed a significant positive relationship between satisfaction and pedagogical atmosphere (p<0.0001). CONCLUSION: This is the first study to investigate nursing students' perceptions of the CLE in undergraduate nursing programs in Nepal. Students were satisfied with the CLE overall, but satisfaction varied by practicum hospital sector. The most influential factor explaining satisfaction was pedagogical atmosphere. PMID- 27006055 TI - Development of a competency framework for evidence-based practice in nursing. AB - BACKGROUND: The measurement of competence in evidence-based practice (EBP) remains challenging to many educators and academics due to the lack of explicit competency criteria. Much uncertainty exists about what specific EBP competencies nurses should meet and how these should be measured. OBJECTIVES: The objectives of this study are to develop a competency framework for measuring evidence-based knowledge and skills in nursing and to elicit the views of health educators/researchers about elements within the framework. DESIGN: A descriptive survey design with questionnaire. PARTICIPANTS AND SETTINGS: Between August and December 2013, forty-two health academics/educators, clinicians; and researchers from the medical and nursing schools at the University of Sydney and the Nurse Teacher's Society in Australia were invited to comment on proposed elements for measuring evidence-based knowledge and skills. METHODS: The EBP competency framework was designed to measure nurses' knowledge and skills for using evidence in practice. Participants were invited to rate their agreement on the structure and relevance of the framework and to state their opinion about the measurement criteria for evidence-based nursing practice. RESULTS: Participant agreement on the structure and relevance of the framework was substantial, ICC: 0.80, 95% CI: 0.67-0.88, P<0.0001. Qualitative analysis of two open-ended survey questions revealed three common themes in participants' opinion of the competency elements: (1) a useful EBP framework; (2) varying expectations of EBP competence; and (3) challenges to EBP implementation. CONCLUSIONS: The findings of this study suggested that the EBP competency framework is of credible value for facilitating evidence-based practice education and research in nursing. However, there remains some uncertainty and disagreement about the levels of EBP competence required for nurses. These challenges further implicate the need for setting a reasonable competency benchmark with a broader group of stakeholders in nursing. PMID- 27006056 TI - Laparoscopic-assisted Retropubic Midurethral Sling Placement: A Technique to Avoid Major Complications. AB - STUDY OBJECTIVE: To describe a technique for the safe placement of retropubic midurethral slings in patients undergoing concomitant laparoscopic surgery in order to avoid major complications associated with this procedure such as bladder perforation and retropubic hematomas. DESIGN: Step-by-step video demonstration of the technique. SETTING: A university tertiary care hospital. PATIENTS: Patients with an indication for retropubic midurethral sling placement because of recurrent stress urinary incontinence, intrinsic sphincter deficiency, or severe pelvic organ prolapse in whom a concomitant laparoscopic surgery has to be performed for other medical conditions. INTERVENTION: Laparoscopic opening and dissection of the Retzius space and insertion of the sling under a laparoscopic view of this space. MEASUREMENTS AND MAIN RESULTS: This technique has been mainly used in patients undergoing laparoscopic pelvic organ prolapse repair. No complications have been identified so far, even in high-risk patients such as those with previous Burch colposuspension. CONCLUSION: This is a simple and reproducible technique for preventing major complications associated with retropubic sling placement in patients undergoing laparoscopic surgery for other reasons. It also permits the immediate detection and even resolution of complications in case any arise. Even high-risk patients may be safely approached. PMID- 27006057 TI - Technical Video: Vesicoscopic Excision of Eroded Tension-free Vaginal Tape. AB - STUDY OBJECTIVE: To show vesicoscopic excision of eroded tension-free vaginal tape (TVT). DESIGN: A technical video showing vesicoscopic excision of eroded TVT (Canadian Task Force Classification level III). SETTING: Urogynecology and Urology Departments, King's College Hospital, London, UK, a tertiary referral center for urogynecology. INTERVENTIONS: A 52-year-old woman presented with suprapubic pain, hematuria, and recurrent urinary tract infections 4 years after TVT insertion for stress urinary incontinence. Cystoscopy revealed exposed tape with calcifications on the right aspect of the bladder. Video urodynamics showed normal bladder function and no stress incontinence. After counseling, she opted to have the portion of tape excised via a vesicoscopic approach. CONCLUSION: Exposed tape is found in up to 4% of women who have undergone TVT procedures because of primary unrecognized bladder injury or secondary erosion [1]. Management of this complication can result in a succession of invasive procedures. In this case, vesicoscopy allowed complete excision of the exposed portion of tape. After mobilization, the bladder wall was closed without tension using Mignot-Grange's extracorporeal knotting technique. The stumps of the tape were buried deeply to prevent recurrent erosion. We have used vesicoscopy since 2007 for a variety of female urogynecologic problems including bladder diverticula, ureteric stenosis, vesicoureteric reflux, foreign body, and vesicovaginal fistulae [2]. So far, we have undertaken 5 tape excisions in 4 patients (1 bilateral exposure). Incontinence has not recurred in any of the women. In conclusion, vesicoscopy can facilitate excision of exposed intravesical tape without risking urethral trauma for recurrent tape exposure. PMID- 27006058 TI - Laparoscopic Repair of Cesarean Scar Defect "Isthmocele". AB - STUDY OBJECTIVE: To demonstrate the technique of laparoscopic repair of a large cesarean scar defect (isthmocele). DESIGN: Case report (Canadian Task Force classification III). SETTING: Cesarean scar defect, also known as an isthmocele, is the result of incomplete healing of the isthmic myometrium after a low transverse uterine incision performed for cesarean section. Although mostly asymptomatic, it may cause menstrual abnormalities (typically postmenstrual spotting), chronic pelvic pain, and secondary infertility. Scar tissue dehiscence, scar pregnancy, and abnormally adherent placenta are some of the obstetric complications associated with this defect. No standardized treatment has yet been accepted. Hysteroscopy and laparoscopy are the minimally invasive approaches currently used to repair the defect. INTERVENTION: A 40-year-old patient, G2P2, presented with postmenstrual spotting and secondary infertility for the past 2 years. She had a history of 2 previous cesarean deliveries. Transvaginal ultrasound revealed a large (2.5 * 1.5 cm) niche. Thickness of the myometrium over the defect was 3 mm. Laparoscopic repair of the uterine defect was performed. The bladder that was densely adherent to the lower uterine segment was freed by careful dissection. The defect was then localized with a sharp curette placed transcervically into the uterus. The curette was pushed anteriorly to delineate the margins of the defect and puncture the ceiling of the isthmocele cavity. The fibrotic tissue that formed the ceiling and the lateral borders of the defect was excised using laparoscopic scissors. Reapproximation of the edges was done with continuous nonlocking 3-0 V-Loc sutures. The procedure took 90 minutes, and there were no associated complications. Postoperative ultrasound performed in the second month after the operation showed a minimal defect measuring 0.5 cm, with a residual myometrial thickness of 7 mm. At the time of this writing, the patient was free of symptoms. CONCLUSION: Laparoscopic repair, although not standardized, is a minimally invasive procedure that can be performed to treat uterine scar defects. Mobilization of the overlying bladder, resection of the isthmocele margins and secondary suturing of the remaining myometrial tissue appears to be an effective treatment option for affected patients. PMID- 27006059 TI - Acute upper limb ischemia, a rare presentation of giant cell arteritis. AB - Giant cell arteritis (GCA) is a systemic large vessel vasculitis, with extracranial arterial involvement described in 10-15% of cases, usually affecting the aorta and its branches. Patients with GCA are more likely to develop aortic aneurysms, but these are rarely present at the time of the diagnosis. We report the case of an 80-year-old Caucasian woman, who reported proximal muscle pain in the arms with morning stiffness of the shoulders for eight months. In the previous two months, she had developed worsening bilateral arm claudication, severe pain, cold extremities and digital necrosis. She had no palpable radial pulses and no measurable blood pressure. The patient had normochromic anemia, erythrocyte sedimentation rate of 120 mm/h, and a negative infectious and autoimmune workup. Computed tomography angiography revealed concentric wall thickening of the aorta extending to the aortic arch branches, particularly the subclavian and axillary arteries, which were severely stenotic, with areas of bilateral occlusion and an aneurysm of the ascending aorta (47 mm). Despite corticosteroid therapy there was progression to acute critical ischemia. She accordingly underwent surgical revascularization using a bilateral carotid humeral bypass. After surgery, corticosteroid therapy was maintained and at six month follow-up she was clinically stable with reduced inflammatory markers. GCA, usually a chronic benign vasculitis, presented exceptionally in this case as acute critical upper limb ischemia, resulting from a massive inflammatory process of the subclavian and axillary arteries, treated with salvage surgical revascularization. PMID- 27006060 TI - Multiple coronary artery aneurysms. PMID- 27006061 TI - Massive hemoptysis as an unusual complication of right heart catheterization: Successful treatment with percutaneous stent. AB - The authors present a case report of successful treatment of pulmonary artery perforation by endovascular stent graft implantation. PMID- 27006062 TI - [Predictors of changes in functional capacity on a cardiac rehabilitation program]. AB - INTRODUCTION: The effectiveness of cardiac rehabilitation programs (CRP) strongly influences the recovery of functional capacity (FC), resulting in improved prognosis and survival. OBJECTIVE: To determine the cardiovascular risk factors that predict changes in FC in patients on CRP. METHODS: We performed a cross sectional descriptive retrospective study of patients who began a CRP between January 2008 and December 2013. The dependent variable was changes in FC estimated in metabolic equivalents (METs) achieved in stress testing at the beginning and end of the phase II program. The independent variables were age, gender, dyslipidemia, diabetes, smoking, body mass index, physical activity level and reason for referral to the CRP. RESULTS: The sample included 1399 patients, of whom 1125 (80.4%) completed the program. FC improved in most patients (93%), with a mean gain of 1.45 +/- 1.19 METs. Patients aged 45 -65 and over 65 years achieved a greater increase in FC compared with other age groups. Patients admitted to the CRP after coronary artery bypass graft surgery obtained a greater improvement in FC compared to patients with acute coronary syndrome. Non-diabetic patients benefited more than diabetic patients. No significant differences were seen between the groups in the other variables. CONCLUSION: This study highlights the need for new and individualized approaches in certain subgroups of patients on CRP. PMID- 27006063 TI - Pulse pressure can predict mortality in advanced heart failure. AB - INTRODUCTION: Pulse pressure (PP) is the difference between systolic and diastolic blood pressure (BP). PP rises markedly after the fifth decade of life. High PP is a risk factor for the development of coronary heart disease and heart failure. The aim of this study was to assess whether PP can be used as a prognostic marker in advanced heart failure. METHODS: We retrospectively studied patients in NYHA class III-IV who were hospitalized in a single heart failure unit between January 2003 and August 2012. Demographic characteristics, laboratory tests, and cardiovascular risk factors were recorded. PP was calculated as the difference between systolic and diastolic BP at admission, and the patients were divided into two groups (group 1: PP >40 mmHg and group 2: PP <=40 mmHg). Median follow-up was 666 +/- 50 days for the occurrence of cardiovascular death and heart transplantation. RESULTS: During follow-up 914 patients in NYHA class III-IV were hospitalized, 520 in group 1 and 394 in group 2. The most important difference between the groups was in left ventricular dysfunction, which was greater in patients with lower PP. On Kaplan-Meier analysis, group 2 had higher mortality (38 vs. 24 patients, log-rank p=0.002). CONCLUSIONS: PP is easily calculated, and enables prediction of cardiovascular death in patients with advanced heart failure. PMID- 27006064 TI - [Primary malignant cardiac tumors: Surgical results]. PMID- 27006065 TI - Dysregulation of brain metal homeostasis in bilirubin-induced neurologic dysfunction. PMID- 27006066 TI - Review about the manganese speciation project related to neurodegeneration: An analytical chemistry approach to increase the knowledge about manganese related parkinsonian symptoms. AB - Neurodegenerative diseases get a growing relevance for societies. But yet the complex multi-factorial mechanisms of these diseases are not fully understood, although it is well accepted that metal ions may play a crucial role. Manganese (Mn) is a transition metal which has essential biochemical functions but from occupational exposure scenarios it appeared that Mn can cause severe neurological damage. This "two-faces"-nature of manganese initiated us to start a project on Mn-speciation, since different element species are known to exhibit different impacts on health. A summary about the step-wise developments and findings from our working group was presented during the annual conference of the German trace element society in 2015. This paper summarizes now the contribution to this conference. It is intended to provide a complete picture of the so far evolved puzzle from our studies regarding manganese, manganese speciation and metabolomics as well as Mn-related mechanisms of neural damage. Doing so, the results of the single studies are now summarized in a connected way and thus their interrelationships are demonstrated. In short terms, we found that Mn exposure leads to an increase of low molecular weight Mn compounds, above all Mn citrate complex, which gets even enriched across neural barriers (NB). At a Mn serum concentration between 1.5 and 1.9MUg/L a carrier switch from Mn-transferrin to Mn-citrate was observed. We concluded that the Mn-citrate complex is that important Mn-carrier to NB which can be found also beyond NB in human cerebrospinal fluid (CSF) or brain of exposed rats. In brain of Mn-exposed rats manganese leads to a decreased iron (Fe) concentration, to a shift from Fe(III) to Fe(II) after long term exposure and thus to a shift toward oxidative stress. This was additionally supported by an increase of markers for oxidative stress, inflammation or lipid peroxidation at increased Mn concentration in brain extracts. Furthermore, glutamate and acetylcholineesterase were elevated and many metabolite concentrations were significantly changed. PMID- 27006067 TI - Using video analysis for concussion surveillance in Australian football. AB - OBJECTIVES: The objectives of the study were to assess the relationship between various player and game factors and risk of concussion; and to assess the reliability of video analysis for mechanistic assessment of concussion in Australian football. DESIGN: Prospective cohort study. METHODS: All impacts and collisions resulting in concussion were identified during the 2011 Australian Football League season. An extensive list of factors for assessment was created based upon previous analysis of concussion in Australian Football League and expert opinions. The authors independently reviewed the video clips and correlation for each factor was examined. RESULTS: A total of 82 concussions were reported in 194 games (rate: 8.7 concussions per 1000 match hours; 95% confidence interval: 6.9-10.5). Player demographics and game variables such as venue, timing of the game (day, night or twilight), quarter, travel status (home or interstate) or score margin did not demonstrate a significant relationship with risk of concussion; although a higher percentage of concussions occurred in the first 5min of game time of the quarter (36.6%), when compared to the last 5min (20.7%). Variables with good inter-rater agreement included position on the ground, circumstances of the injury and cause of the impact. The remainder of the variables assessed had fair-poor inter-rater agreement. Common problems included insufficient or poor quality video and interpretation issues related to the definitions used. CONCLUSIONS: Clear definitions and good quality video from multiple camera angles are required to improve the utility of video analysis for concussion surveillance in Australian football. PMID- 27006068 TI - Stepped care model of pain management and quality of pain care in long-term opioid therapy. AB - Successful organizational improvement processes depend on application of reliable metrics to establish targets and to monitor progress. This study examined the utility of the Pain Care Quality (PCQ) extraction tool in evaluating implementation of the Stepped Care Model for Pain Management at one Veterans Health Administration (VHA) healthcare system over 4 yr and in a non-VHA Federally qualified health center (FQHC) over 2 yr. Two hundred progress notes per year from VHA and 150 notes per year from FQHC primary care prescribers of long-term opioid therapy (>90 consecutive days) were randomly sampled. Each note was coded for the presence or absence of key dimensions of PCQ (i.e., pain assessment, treatment plans, pain reassessment/outcomes, patient education). General estimating equations controlling for provider and facility were used to examine changes in PCQ items over time. Improvements in the VHA were noted in pain reassessment and patient education, with trends in positive directions for all dimensions. Results suggest that the PCQ extraction tool is feasible and may be responsive to efforts to promote organizational improvements in pain care. Future research is indicated to improve the reliability of the PCQ extraction tool and enhance its usability. PMID- 27006069 TI - Thermophysical effects of water driven copper nanoparticles on MHD axisymmetric permeable shrinking sheet: Dual-nature study. AB - The present study is dedicated to analyze the dual-nature solutions of the axisymmetric flow of a magneto-hydrodynamics (MHD) nanofluid over a permeable shrinking sheet. In those phenomena where the fluid flow is due to the shrinking surface, some reverse behaviors of the flow arise because of vorticity effects. Despite of heat transfer analysis, the main purpose of the present study is to attain the solutions of the complex nature problem that appear in reverse flow phenomena. Thermophysical properties of both base fluid (water) and nanoparticles (copper) are also taken into account. By means of similarity transformation, partial differential equations are converted into a system of coupled nonlinear ordinary differential equations and then solved via the Runge-Kutta method. These results are divided separately into two cases: the first one is the unidirectional shrinking along the surface (m = 1) and the other one is for axisymmetric shrinking phenomena (m = 2) . To enhance the thermal conductivity of base fluid, nanoparticle volume fractions (0<=phi <= 0.2)) are incorporated within the base fluid. The numerical investigation explores the condition of existence, non-existence and the duality of similarity solution depends upon the range of suction parameter (S) and Hartmann number (M). The reduced skin friction coefficient and local Nusselt number are plotted to analyze the fluid flow and heat transfer at the surface of the shrinking sheet. Streamlines and isotherms are also plotted against the engineering control parameters to analyze the flow behavior and heat transfer within the whole domain. Throughout this analysis it is found that both nanoparticle volume fraction and Hartmann number are increasing functions of both skin friction coefficient and Nusselt number. PMID- 27006070 TI - Effective Downsizing of a Gastroesophageal GIST Using Neoadjuvant Imatinib Mesylate: a Case Report. PMID- 27006071 TI - Aging, inflammation, stem cells, and bone healing. AB - Complex interactions among cells of the monocyte-macrophage-osteoclast lineage and the mesenchymal stem cell-osteoblast lineage play a major role in the pathophysiology of bone healing. Whereas the former lineage directs inflammatory events and bone resorption, the latter represents a source of cells for bone regeneration and immune modulation. Both of these lineages are affected by increasing age, which is associated with higher baseline levels of inflammatory mediators, and a significant reduction in osteogenic capabilities. Given the above, fracture healing, osteoporosis, and other related events in the elderly present numerous challenges, which potentially could be aided by new therapeutic approaches to modulate both inflammation and bone regeneration. PMID- 27006072 TI - A novel prognostic inflammation score predicts outcomes in patients with ovarian cancer. AB - BACKGROUND: Systemic inflammation and host immunological nutritional status play important roles in the tumorigenesis of malignant cancer. A novel prognostic inflammation score (PIS) based on preoperative serum albumin and neutrophil to lymphocyte ratio (NLR) was designed. We explored its prognostic value in ovarian cancer. METHODS: 143 patients with ovarian cancer were enrolled in this retrospective study. The association of the PIS with clinicopathologic parameters was analyzed. The prognostic significance was determined by univariate and multivariate cox survival analyses. RESULTS: Both univariate and multivariate analyses showed that NLR and albumin were independent prognostic factors for overall survival (OS) and progression-free survival (PFS). An inverse correlation was observed between the NLR and serum albumin concentration. The novel prognostic inflammation score (PIS) was shown to be a significant predictor for OS and PFS (both P<0.001) according to multivariate analysis. Additionally, low PIS was associated with advanced tumor stage (P<0.001), metastasis (P<0.001) and preoperative high PLR (P<0.001). CONCLUSIONS: The PIS is a novel but promising prognostic score in ovarian cancer. It is a significant prognostic marker adjusted for clinicopathologic characteristics to further identify patients' survival differences. PMID- 27006073 TI - Towards next generation maggot debridement therapy: transgenic Lucilia sericata larvae that produce and secrete a human growth factor. AB - BACKGROUND: Diabetes and its concurrent complications impact a significant proportion of the population of the US and create a large financial burden on the American health care system. FDA-approved maggot debridement therapy (MDT), the application of sterile laboratory-reared Lucilia sericata (green bottle fly) larvae to wounds, is a cost-effective and successful treatment for diabetic foot ulcers and other medical conditions. Human platelet derived growth factor-BB (PDGF-BB) is a secreted dimeric peptide growth factor that binds the PDGF receptor. PDGF-BB stimulates cell proliferation and survival, promotes wound healing, and has been investigated as a possible topical treatment for non healing wounds. Genetic engineering has allowed for expression and secretion of human growth factors and other proteins in transgenic insects. Here, we present a novel concept in MDT technology that combines the established benefits of MDT with the power of genetic engineering to promote healing. The focus of this study is to create and characterize strains of transgenic L. sericata that express and secrete PDGF-BB at detectable levels in adult hemolymph, whole larval lysate, and maggot excretions/ secretions (ES), with potential for clinical utility in wound healing. RESULTS: We have engineered and confirmed transgene insertion in several strains of L. sericata that express human PDGF-BB. Using a heat-inducible promoter to control the pdgf-b gene, pdgf-b mRNA was detected via semi quantitative PCR upon heat shock. PDGF-BB protein was also detectable in larval lysates and adult hemolymph but not larval ES. An alternative, tetracycline repressible pdgf-b system mediated expression of pdgf-b mRNA when maggots were raised on diet that lacked tetracycline. Further, PDGF-BB protein was readily detected in whole larval lysate as well as larval ES. CONCLUSIONS: Here we show robust, inducible expression and production of human PDGF-BB protein from two conditional expression systems in transgenic L. sericata larvae. The tetracycline repressible system appears to be the most promising as PDGF-BB protein was detectable in larval ES following induction. Our system could potentially be used to deliver a variety of growth factors and anti-microbial peptides to the wound environment with the aim of enhancing wound healing, thereby improving patient outcome in a cost-effective manner. PMID- 27006074 TI - Discovering the cost of care: consumer, provider, and retailer surveys shed light on the determinants of malaria health-seeking behaviours. AB - BACKGROUND: The growing threat of insecticide resistance in mosquitoes and drug resistance in the Plasmodium parasites increases the importance of ensuring appropriate malaria case management and enabling positive health-seeking behaviour. Treatment-seeking behaviours are poorly characterized in malaria endemic regions that have been the focus of intensive control and elimination campaigns. This study uses a comprehensive approach to shed light on the determinants of malaria treatment-seeking behaviours from different perspectives. METHODS: The authors conducted cross-sectional surveys from 832 households, fifteen health centers, and 135 retailers across three sites in the Emuhaya and Kakamega districts of the western Kenyan highlands. Participants were recruited via random sampling and data were collected with the use of a structured questionnaire about malaria treatment-seeking behaviour. All households, healthcare facilities, and retailers were mapped using a handheld GPS and a GIS algorithm was used to calculate "walk distance" based on the Tobler rule; an estimate of this distance was used to calculate the travel time used in the analyses. RESULTS: Across the three sites, 47.5-78.9% of the residents sought diagnosis and treatment at hospitals, clinics, or dispensaries; 6.3-26.1% of the residents sought malaria care only at pharmaceutical retailers. Overall, 40.3 59.4% of residents reported delaying seeking care for more than 24 h after fever onset. After adjustment, residents who chose to visit a pharmaceutical retail facility rather than a hospital were 121 and 307% more likely to delay seeking medical care after fever onset than those who reported choosing a healthcare facility for treatment. No significant association was found between travel time and delay in seeking care. The surveys of the healthcare facilities indicated an average total cost per patient per visit was 112 KES ($1.40 US) for public facilities and 165 KES ($2.06 US) for private facilities. CONCLUSION: Understanding the local health behaviours that perpetuate transmission of malaria will help develop targeted preventive measures and educational interventions that can empower the residents with the knowledge needed to combat malaria in a safe and effective manner. Ensuring patient access to health care facilities in countries with high disease burdens has broader implications on measures of equity and on public health prevention methodologies. PMID- 27006075 TI - Using the Nine Common Themes of Good Practice checklist as a tool for evaluating the research priority setting process of a provincial research and program evaluation program. AB - BACKGROUND: Given the context-specific nature of health research prioritization and the obligation to effectively allocate resources to initiatives that will achieve the greatest impact, evaluation of priority setting processes can refine and strengthen such exercises and their outcomes. However, guidance is needed on evaluation tools that can be applied to research priority setting. This paper describes the adaption and application of a conceptual framework to evaluate a research priority setting exercise operating within the public health sector in Ontario, Canada. METHODS: The Nine Common Themes of Good Practice checklist, described by Viergever et al. (Health Res Policy Syst 8:36, 2010) was used as the conceptual framework to evaluate the research priority setting process developed for the Locally Driven Collaborative Projects (LDCP) program in Ontario, Canada. Multiple data sources were used to inform the evaluation, including a review of selected priority setting approaches, surveys with priority setting participants, document review, and consultation with the program advisory committee. RESULTS: The evaluation assisted in identifying improvements to six elements of the LDCP priority setting process. The modifications were aimed at improving inclusiveness, information gathering practices, planning for project implementation, and evaluation. In addition, the findings identified that the timing of priority setting activities and level of control over the process were key factors that influenced the ability to effectively implement changes. CONCLUSIONS: The findings demonstrate the novel adaptation and application of the 'Nine Common Themes of Good Practice checklist' as a tool for evaluating a research priority setting exercise. The tool can guide the development of evaluation questions and enables the assessment of key constructs related to the design and delivery of a research priority setting process. PMID- 27006076 TI - Benchmarking of surgical complications in gynaecological oncology: prospective multicentre study. AB - OBJECTIVE: To explore the impact of risk-adjustment on surgical complication rates (CRs) for benchmarking gynaecological oncology centres. DESIGN: Prospective cohort study. SETTING: Ten UK accredited gynaecological oncology centres. POPULATION: Women undergoing major surgery on a gynaecological oncology operating list. METHODS: Patient co-morbidity, surgical procedures and intra-operative (IntraOp) complications were recorded contemporaneously by surgeons for 2948 major surgical procedures. Postoperative (PostOp) complications were collected from hospitals and patients. Risk-prediction models for IntraOp and PostOp complications were created using penalised (lasso) logistic regression using over 30 potential patient/surgical risk factors. MAIN OUTCOME MEASURES: Observed and risk-adjusted IntraOp and PostOp CRs for individual hospitals were calculated. Benchmarking using colour-coded funnel plots and observed-to-expected ratios was undertaken. RESULTS: Overall, IntraOp CR was 4.7% (95% CI 4.0-5.6) and PostOp CR was 25.7% (95% CI 23.7-28.2). The observed CRs for all hospitals were under the upper 95% control limit for both IntraOp and PostOp funnel plots. Risk-adjustment and use of observed-to-expected ratio resulted in one hospital moving to the >95 98% CI (red) band for IntraOp CRs. Use of only hospital-reported data for PostOp CRs would have resulted in one hospital being unfairly allocated to the red band. There was little concordance between IntraOp and PostOp CRs. CONCLUSION: The funnel plots and overall IntraOp (~5%) and PostOp (~26%) CRs could be used for benchmarking gynaecological oncology centres. Hospital benchmarking using risk adjusted CRs allows fairer institutional comparison. IntraOp and PostOp CRs are best assessed separately. As hospital under-reporting is common for postoperative complications, use of patient-reported outcomes is important. TWEETABLE ABSTRACT: Risk-adjusted benchmarking of surgical complications for ten UK gynaecological oncology centres allows fairer comparison. PMID- 27006077 TI - McTwo: a two-step feature selection algorithm based on maximal information coefficient. AB - BACKGROUND: High-throughput bio-OMIC technologies are producing high-dimension data from bio-samples at an ever increasing rate, whereas the training sample number in a traditional experiment remains small due to various difficulties. This "large p, small n" paradigm in the area of biomedical "big data" may be at least partly solved by feature selection algorithms, which select only features significantly associated with phenotypes. Feature selection is an NP-hard problem. Due to the exponentially increased time requirement for finding the globally optimal solution, all the existing feature selection algorithms employ heuristic rules to find locally optimal solutions, and their solutions achieve different performances on different datasets. RESULTS: This work describes a feature selection algorithm based on a recently published correlation measurement, Maximal Information Coefficient (MIC). The proposed algorithm, McTwo, aims to select features associated with phenotypes, independently of each other, and achieving high classification performance of the nearest neighbor algorithm. Based on the comparative study of 17 datasets, McTwo performs about as well as or better than existing algorithms, with significantly reduced numbers of selected features. The features selected by McTwo also appear to have particular biomedical relevance to the phenotypes from the literature. CONCLUSION: McTwo selects a feature subset with very good classification performance, as well as a small feature number. So McTwo may represent a complementary feature selection algorithm for the high-dimensional biomedical datasets. PMID- 27006078 TI - Effect of Age, Estrogen Status, and Late-Life GPER Activation on Cardiac Structure and Function in the Fischer344*Brown Norway Female Rat. AB - Age-associated changes in cardiac structure and function, together with estrogen loss, contribute to the progression of heart failure with preserved ejection fraction in older women. To investigate the effects of aging and estrogen loss on the development of its precursor, asymptomatic left ventricular diastolic dysfunction, echocardiograms were performed in 10 middle-aged (20 months) and 30 old-aged (30 months) female Fischer344*Brown-Norway rats, 4 and 8 weeks after ovariectomy (OVX) and sham procedures (gonads left intact). The cardioprotective potential of administering chronic G1, the selective agonist to the new G-protein coupled estrogen receptor (GPER), was further evaluated in old rats (Old-OVX+G1) versus age-matched, vehicle-treated OVX and gonadal intact rats. Advanced age and estrogen loss led to decreases in myocardial relaxation and elevations in filling pressure, in part, due to reductions in phosphorylated phospholamban and increases in cardiac collagen deposition. Eight weeks of G-protein-coupled estrogen receptor activation in Old-OVX+G1 rats reversed the adverse effects of age and estrogen loss on myocardial relaxation through increases in sarcoplasmic reticulum Ca2+ ATPase expression and reductions in interstitial fibrosis. These findings may explain the preponderance of heart failure with preserved ejection fraction in older postmenopausal women and provide a promising, late-life therapeutic target to reverse or halt the progression of left ventricular diastolic dysfunction. PMID- 27006079 TI - Four Distinct Health Profiles in Older Patients With Cancer: Latent Class Analysis of the Prospective ELCAPA Cohort. AB - BACKGROUND: Several studies have evaluated the independent prognostic value of impairments in single geriatric-assessment (GA) components in elderly cancer patients. None identified homogeneous subgroups. Our aims were to identify such subgroups based on combinations of GA components and to assess their associations with treatment decisions, admission, and death. METHODS: We prospectively included 1,021 patients aged >=70 years who had solid or hematologic malignancies and who underwent a GA in one of two French teaching hospitals. Two geriatricians independently selected candidate GA parameters for latent class analysis, which was then performed on the 821 cases without missing data. Age, gender, tumor site, metastatic status, and inpatient versus outpatient status were used as active covariates and predictors of class membership. Outcomes were cancer treatment decisions, overall 1-year mortality, and 6-month unscheduled admissions. Sensitivity analyses were performed on the overall population of 1,021 patients and on 375 newly enrolled patients. RESULTS: We identified four classes: relatively healthy (LC1, 28%), malnourished (LC2, 36%), cognitive and mood impaired (LC3, 15%), and globally impaired (LC4, 21%). Tumor site, metastatic status, age, and in/outpatient status independently predicted class membership (p < .001). In adjusted pairwise comparisons, compared to LC1, the three other LCs were associated with higher risks of palliative treatment, death, and unscheduled admission (p <= .05). LC4 was associated with 1-year mortality and palliative treatment compared to LC2 and LC3 (p <= .05). CONCLUSION: We identified four health profiles that may help physicians select cancer treatments and geriatric interventions. Researchers may find these profiles useful for stratifying patients in clinical trials. PMID- 27006080 TI - Laser Spectroscopic Study of Cold Gas-Phase Host-Guest Complexes of Crown Ethers. AB - The structure, molecular recognition, and inclusion effect on the photophysics of guest species are investigated for neutral and ionic cold host-guest complexes of crown ethers (CEs) in the gas phase. Here, the cold neutral host-guest complexes are produced by a supersonic expansion technique and the cold ionic complexes are generated by the combination of electrospray ionization (ESI) and a cryogenically cooled ion trap. The host species are 3n-crown-n (3nCn; n = 4, 5, 6, 8) and (di)benzo-3n-crown-n ((D)B3nCn; n = 4, 5, 6, 8). For neutral guests, we have chosen water and aromatic molecules, such as phenol and benzenediols, and as ionic species we have chosen alkali-metal ions (M(+) ). The electronic spectra and isomer-specific vibrational spectra for the complexes are observed with various laser spectroscopic methods: laser-induced fluorescence (LIF); ultraviolet-ultraviolet hole-burning (UV-UV HB); and IR-UV double resonance (IR UV DR) spectroscopy. The obtained spectra are analyzed with the aid of quantum chemical calculations. We will discuss how the host and guest species change their flexible structures for forming best-fit stable complexes (induced fitting) and what kinds of interactions are operating for the stabilization of the complexes. For the alkali metal ion*CE complexes, we investigate the solvation effect by attaching water molecules. In addition to the ground-state stabilization problem, we will show that the complexation leads to a drastic effect on the excited-state electronic structure and dynamics of the guest species, which we call a "cage-like effect". PMID- 27006081 TI - Quantification of ethanol in plasma by electrochemical detection with an unmodified screen printed carbon electrode. AB - Simple, rapid and accurate detection of ethanol concentration in blood is very crucial in the diagnosis and management of potential acute ethanol intoxication patients. A novel electrochemical detection method was developed for the quantification of ethanol in human plasma with disposable unmodified screen printed carbon electrode (SPCE) without sample preparation procedure. Ethanol was detected indirectly by the reaction product of ethanol dehydrogenase (ADH) and cofactor nicotinamide adenine dinucleotide (NAD(+)). Method validation indicated good quantitation precisions with intra-day and inter-day relative standard deviations of <=9.4% and 8.0%, respectively. Ethanol concentration in plasma is linear ranging from 0.10 to 3.20 mg/mL, and the detection limit is 40.0 MUg/mL (S/N > 3). The method shows satisfactory correlation with the reference method of headspace gas chromatography in twenty human plasma samples (correlation coefficient 0.9311). The proposed method could be applied to diagnose acute ethanol toxicity or ethanol-related death. PMID- 27006083 TI - Stability of Monodisperse Phospholipid-Coated Microbubbles Formed by Flow Focusing at High Production Rates. AB - Monodisperse microbubble ultrasound contrast agents may dramatically increase the sensitivity and efficiency in ultrasound imaging and therapy. They can be produced directly in a microfluidic flow-focusing device, but questions remain as to the interfacial chemistry, such as the formation and development of the phospholipid monolayer coating over time. Here, we demonstrate the synthesis of monodisperse bubbles with radii of 2-10 MUm at production rates ranging from 10(4) to 10(6) bubbles/s. All bubbles were found to dissolve to a stable final radius 2.55 times smaller than their initial radius, independent of the nozzle size and shear rate, indicating that the monolayer self-assembles prior to leaving the nozzle. The corresponding decrease in surface area by a factor 6.6 reveals that lipid molecules are adsorbed to the gas-liquid interface in the disordered expanded state, and they become mechanically compressed by Laplace pressure-driven bubble dissolution to a more ordered condensed state with near zero surface tension. Acoustic characterization of the stabilized microbubbles revealed that their shell stiffness gradually increased from 0.8 to 2.5 N/m with increasing number of insonations through the selective loss of the more soluble lipopolymer molecules. This work therefore demonstrates high-throughput production of clinically relevant monodisperse contrast microbubbles with excellent control over phospholipid monolayer elasticity and microbubble resonance. PMID- 27006082 TI - Recent advances and long-standing problems in detecting oxidative damage and reactive oxygen species in skeletal muscle. AB - An increasingly sophisticated array of approaches are now available for the study of the activities of reactive oxygen species and oxidative modifications in skeletal muscle, but the most up-to-date techniques are not readily available to many researchers in this field due to their requirement for sophisticated mass spectrometry, imaging or other high cost technologies. Most papers published therefore rely on a number of established approaches although the choice of approach is also clearly dependent upon the experimental model and access to skeletal muscle that is available to the investigator, how much detail is required and the overall question to be addressed. Numerous reports have described the problems associated with some of the popular approaches that are widely followed, including measurement of thiobarbituric acid substances and the sole use of fluorescence-based probes such as dichlorodihydrofluorescein. This brief review reports the areas in which methods are improving to allow valid assessments to made in this area and indicates some of the more recent developments that provide alternative ways to assess the activity of individual species and endpoints in the various experimental models that may be examined. PMID- 27006084 TI - Response of the seated human body to whole-body vertical vibration: discomfort caused by mechanical shocks. AB - The frequency dependence of discomfort caused by vertical mechanical shocks has been investigated with 20 seated males exposed to upward and downward shocks at 13 fundamental frequencies (1-16 Hz) and 18 magnitudes (+/-0.12 to +/-8.3 ms-2). The rate of growth of discomfort with increasing shock magnitude depended on the fundamental frequency of the shocks, so the frequency dependence of equivalent comfort contours (for both vertical acceleration and vertical force measured at the seat) varied with shock magnitude. The rate of growth of discomfort was similar for acceleration and force, upward and downward shocks, and lower and higher magnitude shocks. The frequency dependence of discomfort from shocks differs from that of sinusoidal vibrations having the same fundamental frequencies. This arises in part from the frequency content of the shock. Frequency weighting Wb in BS 6841:1987 and ISO 2631-1:1997 provided reasonable estimates of the discomfort caused by the shocks investigated in this study. Practitioner Summary: No single frequency weighting can accurately predict the discomfort caused by mechanical shocks over wide ranges of shock magnitude, but vibration dose values with frequency weighting Wb provide reasonable estimates of discomfort caused by shocks similar to those investigated in this study with peak accelerations well below 1 g. PMID- 27006086 TI - Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression. AB - Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury. PMID- 27006085 TI - The Effect of rhCygb on CCl4-Induced Hepatic Fibrogenesis in Rat. AB - This study aims to investigate whether the use of recombinant human cytoglobin (rhCygb) impact on hepatic fibrogenesis caused by CCl4. SD (n = 150) rats were randomly divided into three groups of normal, CCl4 model and rhCygb groups. After model establishment, rats in rhCygb groups were administered daily with rhCygb (2 mg/kg, s.c.). Histological lesions were staged according to metavir. Serum parameters including ALT, AST, HA, LN, Col III and Col IV were determined. The liver proteins were separated by 2-DE and identified. As a result, the stage of hepatic damage and liver fibrosis in rhCygb groups were significantly milder than that in CCl4 model groups. Meanwhile, rhCygb dramatically reversed serum levels of ALT and AST, and also markedly decreased the liver fibrosis markers levels of LN, HA, Col III and Col IV. In 2-DE, 33 proteins among three groups with the same changing tendency in normal and rhCygb treated groups compared with CCl4 model group were identified. GO analysis showed that several identified proteins involved in oxidative stress pathway. The study provides new insights and data for administration of rhCygb reversing CCl4-induced liver fibrosis suggesting that rhCygb might be used in the treatment of liver fibrosis. PMID- 27006087 TI - Structural and biochemical insights into 7beta-hydroxysteroid dehydrogenase stereoselectivity. AB - Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo- and regio-selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7beta hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active-site accessibility, the bases of the specificity for NADP(+) , and the general architecture of the steroid binding site. Comparison with 7alpha hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C-terminal extension reshapes the substrate site of the beta-selective enzyme, possibly leading to an inverted orientation of the bound substrate. Proteins 2016; 84:859-865. (c) 2016 Wiley Periodicals, Inc. PMID- 27006089 TI - Implementation of quantum and classical discrete fractional Fourier transforms. AB - Fourier transforms, integer and fractional, are ubiquitous mathematical tools in basic and applied science. Certainly, since the ordinary Fourier transform is merely a particular case of a continuous set of fractional Fourier domains, every property and application of the ordinary Fourier transform becomes a special case of the fractional Fourier transform. Despite the great practical importance of the discrete Fourier transform, implementation of fractional orders of the corresponding discrete operation has been elusive. Here we report classical and quantum optical realizations of the discrete fractional Fourier transform. In the context of classical optics, we implement discrete fractional Fourier transforms of exemplary wave functions and experimentally demonstrate the shift theorem. Moreover, we apply this approach in the quantum realm to Fourier transform separable and path-entangled biphoton wave functions. The proposed approach is versatile and could find applications in various fields where Fourier transforms are essential tools. PMID- 27006090 TI - Socioeconomic status and fertility intentions among Chinese women with one child. AB - There has been a lack of socioeconomic status (SES) disparity analysis on women in China with only one child, the family planning target population. In 2008, the National Research Institute for Family Planning of China conducted a study investigating the relationship between SES and fertility intentions among 17,093 women in China who already had one child. A questionnaire was used to collect information on SES and fertility intentions, and logistic regression models were used to estimate the odds ratios and 95% CIs of fertility intentions according to SES. Compared with female farmers, women in other occupations intended to have fewer children (p < 0.05). Additionally, compared with women with low educational level (illiterate/primary), women with secondary and postsecondary education intended to have fewer children (p < 0.05) (OR = 0.70; 95% CI: 0.61-0.81 and OR = 0.56; 95% CI 0.47-0.66). A mother's education level was significantly and negatively associated with fertility intentions after adjustment for potential confounders (p < 0.05). Among Chinese women who had one child, the women with higher SES (e.g. higher educational level) had lower fertility intentions. There is an SES disparity in the fertility intention among Chinese women who already have one child. China's policy-makers should consider increasing high SES women's fertility intention. PMID- 27006091 TI - An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug-drug and drug-herb interaction by LC ESI/MS/MS. AB - The aim of the present study was to evaluate the contribution of metabolites to drug-drug interaction and drug-herb interaction using the inhibition of CYP2D6 and CYP3A4 by metoprolol (MET) and its metabolites. The peak concentrations of unbound plasma concentration of MET, alpha-hydroxy metoprolol (HM), O-desmethyl metoprolol (ODM) and N-desisopropyl metoprolol (DIM) were 90.37 +/- 2.69, 33.32 +/- 1.92, 16.93 +/- 1.70 and 7.96 +/- 0.94 ng/mL, respectively. The metabolites identified, HM and ODM, had a ratio of metabolic area under the concentration time curve (AUC) to parent AUC of >=0.25 when either total or unbound concentration of metabolite was considered. In vitro CYP2D6 and CYP3A4 inhibition by MET, HM and ODM study revealed that MET, HM and ODM were not inhibitors of CYP3A4-catalyzed midazolam metabolism and CYP2D6-catalyzed dextromethorphan metabolism. However, DIM only met the criteria of >10% of the total drug related material and <25% of the parent using unbound concentrations. If CYP inhibition testing is solely based on metabolite exposure, DIM metabolite would probably not be considered. However, the present study has demonstrated that DIM contributes significantly to in vitro drug-drug interaction. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27006092 TI - Increased prevalence of some birth defects in Korea, 2009-2010. AB - BACKGROUND: Birth defects are a leading cause of neonatal and infant mortality, and several studies have indicated an increase in the prevalence of birth defects; more recent investigations have suggested that the trends of some defects are increasing in rapidly industrialized areas. This study estimates the prevalence rate and types of birth defects in Korea. METHODS: This study used medical insurance benefit data of 403,250 infants aged less than one year from the National Health Insurance Corporation from seven metropolitan areas in Korea for 2009 and 2010. RESULTS: The prevalence rate of birth defects was 548.3 per 10,000 births (95% CI: 541.1-555.6), 306.8 among boys and 241.5 among girls. Anomalies of the circulatory system (particularly septal defects) were the most common (180.8 per 10,000), followed by defects of the genitourinary tract (130.1 per 10,000) (particularly obstructive genitourinary and undescended testis), musculoskeletal system (105.7 per 10,000), digestive system (24.7 per 10,000), and central nervous system (15.6 per 10,000). CONCLUSIONS: Relatively higher rates of some birth defects were found in the metropolitan areas. The high differences of birth prevalences for septal heart defects and undescended testis are probably due in part to progress in clinical management and more frequent prenatal diagnosis. Environmental exposure might play a critical role in the development of some birth defects. In attempting to describe the prevalence and spatio-temporal variations of birth defects in Korea, establishment of a registry system of birth defects and environmental surveillance are needed. PMID- 27006093 TI - Cross-modal symbolic processing can elicit either an N2 or a protracted N2/N400 response. AB - A cross-modal symbolic paradigm was used to elicit EEG activity related to semantic incongruence. Twenty-five undergraduate students viewed pairings of visual lexical cues (e.g., DOG) with congruent (50% of trials) or incongruent (50%) auditory nonlexical stimuli (animal vocalizations; e.g., sound of a dog woofing or a cat meowing). In one condition, many different pairs of congruent/incongruent stimuli were shown, whereas in a second condition only two pairs of stimuli were repeatedly shown. A typical N400-like pattern of incongruence-related activity (including activity in the N2 time window) was evident in the condition using many stimuli, whereas the incongruence-related activity in the two-stimuli condition was confined to differential N2-like activity. A supplementary analysis excluded stimulus characteristics as the source of this differential activity between conditions. We found that a single individual performing a fixed task can demonstrate either a protracted N400-like pattern of activity or a more temporally focused N2-like pattern of activity in response to the same stimulus, which suggests that the N2 may be a precursor to the protracted N400 response. PMID- 27006094 TI - A novel small molecule, Rosline, inhibits growth and induces caspase-dependent apoptosis in human lung cancer cells A549 through a reactive oxygen species dependent mechanism. AB - Chemical screening using synthetic small molecule libraries has provided a huge amount of novel active molecules. It generates lead compound for drug development and brings focus on molecules for mechanistic investigations on many otherwise intangible biological processes. In this study, using non-small cell lung cancer cell A549 to screen against a structurally novel and diverse synthetic small molecule library of 2,400 compounds, we identified a molecule named rosline that has strong anti-proliferation activity on A549 cells with a 50% cell growth inhibitory concentration (IC50 ) of 2.87 +/- 0.39 uM. We showed that rosline treatment increased the number of Annexin V-positive staining cell, as well as G2/M arrest in their cell cycle progression. Further, we have demonstrated that rosline induces a decrease of mitochondrial membrane potential (Deltaphim ) and an increase of caspases 3/7 and 9 activities in A549 cells, although having no effect on the activity of caspase 8. Moreover, we found that rosline could induce the production of reactive oxygen species (ROS) and inhibit the phosphorylation of signaling molecule Akt in A549 cells. Alternatively, an antioxidant N-acetyl-L cysteine (NAC) significantly attenuated rosline's effects on the mitochondrial membrane potential, caspases 3/7 and 9 activities, cell viabilities and the phosphorylation of Akt. Our results demonstrated that ROS played an important role in the apoptosis of A549 cells induced by rosline. PMID- 27006095 TI - Oxime conjugation in protein chemistry: from carbonyl incorporation to nucleophilic catalysis. AB - Use of oxime forming reactions has become a widely applied strategy for peptide and protein bioconjugation. The efficiency of the reaction and robust stability of the oxime product has led to the development of a growing list of methods to introduce the required ketone or aldehyde functionality site specifically into proteins. Early methods focused on site-specific oxidation of an N-terminal serine or threonine and more recently transamination methods have been developed to convert a broader set of N-terminal amino acids into a ketone or aldehyde. More recently, site-specific modification of protein has been attained through engineering enzymes involved in posttranslational modifications in order to accommodate aldehyde-containing substrates. Similarly, a growing list of unnatural amino acids can be introduced through development of selective amino acyl tRNA synthetase/tRNA pairs combined with codon reassignment. In the case of glycoproteins, glycans can be selectively modified chemically or enzymatically to introduce aldehyde functional groups. Finally, the total chemical synthesis of proteins complements these biological and chemoenzymatic approaches. Once introduced, the oxime ligation of these aldehyde and ketone groups can be catalyzed by aniline or a variety of aniline derivatives to tune the activity, pH preference, stability and solubility of the catalyst. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27006096 TI - Beyond Clusters: Supramolecular Networks Self-Assembled from Nanosized Silver Clusters and Inorganic Anions. AB - Assembly of small clusters into rigid bodies with precise shape and symmetry has been witnessed by the significant advances in cluster-based metal-organic frameworks (MOFs), however, nanosized silver cluster based MOFs remain largely unexplored. Herein, two anion-templated silver clusters, CO3 @Ag20 and SO4 @Ag22 , were ingeniously incorporated into a 2D sql lattice (1, [CO3 @Ag20 (iPrS)10 (NO3 )8 (DMF)2 ]n ) and an unprecedented 3D two-fold interpenetrated dia network (2, [SO4 @Ag22 (iPrS)12 (NO3 )6 ?2 NO3 ]n ), respectively, under mild solvothermal conditions. Their atomically precise structures were confirmed by single-crystal X-ray diffraction analysis and further consolidated by IR spectroscopy, thermogravimetric analysis (TGA), and elemental analysis. Each drum like CO3 @Ag20 cluster is extended by twelve NO3 (-) ions to form the 2D sql lattice of 1, whereas each ball-shaped SO4 @Ag22 cluster with a twisted truncated tetrahedral geometry is pillared by four [Ag6 (NO3 )3 ] triangular prisms to form the 3D interpenetrated dia network of 2. Notably, 2 is the first interpenetrated 3D MOF constructed from silver clusters. These results demonstrate the dual role of the anions, which not only internally act as anion templates to induce the formation of silver thiolate clusters but also externally extend the cluster units into the rigid networks. The photoluminescent and electrochemical properties of 2 are discussed in detail. PMID- 27006097 TI - Processed stigmas of Crocus sativus L. imaged by MALDI-based MS. AB - The processed, i.e. dried under certain conditions, stigmas of Crocus sativus L. are one of the most expensive plant parts used commercially. For the color, aroma and biological activity a very complex mixture of glycolipids termed crocins are responsible. Therefore studying structural composition and distribution in the commercial plant material is of great interest. We showed successfully the application of a MALDI-based mass spectrometric imaging (MSI) approach for stigmas towards different crocin species. MSI opens up the investigation of processed plant materials in various fields allowing studying the processing in detail as well as adulteration attempts (which are quite frequent due to the price of the material). Furthermore, we could demonstrate that a similar number of crocins present in stigmas could be detected by MALDI MSI compared to the classical approach of analyzing the solvent-extract of stigmas by MALDI-MS. PMID- 27006098 TI - Pea aphid Acyrthosiphon pisum sequesters plant-derived secondary metabolite L DOPA for wound healing and UVA resistance. AB - Herbivores can ingest and store plant-synthesized toxic compounds in their bodies, and sequester those compounds for their own benefits. The broad bean, Vicia faba L., contains a high quantity of L-DOPA (L-3,4-dihydroxyphenylalanine), which is toxic to many insects. However, the pea aphid, Acyrthosiphon pisum, can feed on V. faba normally, whereas many other aphid species could not. In this study, we investigated how A. pisum utilizes plant-derived L-DOPA for their own benefit. L-DOPA concentrations in V. faba and A. pisum were analyzed to prove L DOPA sequestration. L-DOPA toxicity was bioassayed using an artificial diet containing high concentrations of L-DOPA. We found that A. pisum could effectively adapt and store L-DOPA, transmit it from one generation to the next. We also found that L-DOPA sequestration verity differed in different morphs of A. pisum. After analyzing the melanization efficiency in wounds, mortality and deformity of the aphids at different concentrations of L-DOPA under ultraviolet radiation (UVA 365.0 nm for 30 min), we found that A. pisum could enhance L-DOPA assimilation for wound healing and UVA-radiation protection. Therefore, we conclude that A. pisum could acquire L-DOPA and use it to prevent UVA damage. This study reveals a successful co-evolution between A. pisum and V. faba. PMID- 27006099 TI - Two phenyls are better than one or three: synthesis and application of terminal olefin-oxazoline (TOlefOx) ligands. AB - A novel terminal olefin-oxazoline ligand was introduced into rhodium-catalyzed asymmetric conjugate addition of arylboronic acids to enones and gave excellent enantioselectivities. The two phenyls proved better than one or three in ligand evaluations. PMID- 27006100 TI - Induction of cell cycle arrest and apoptosis with downregulation of Hsp90 client proteins and histone modification by 4beta-hydroxywithanolide E isolated from Physalis peruviana. AB - SCOPE: Physalis peruviana (Solanaceae) is used for culinary and medicinal purposes. We currently report withanolides, isolated from P. peruviana, inhibit the growth of colon cancer monolayer and spheroid cultures. A detailed mechanistic evaluation was performed with 4beta-hydroxywithanolide E (4HWE). METHODS AND RESULTS: Treatment of HT-29 cells with low concentrations of 4HWE inhibited growth while enhancing levels of p21(Waf1/Cip1) and reducing levels of several cell cycle-related proteins. Apoptosis was induced at higher concentrations. In addition, 4HWE treatment downregulated the levels of Hsp90 client proteins. Nuclear sirtuin 1 (SIRT1) was increased and histone H3 acetylated at lysine 9 was decreased. An additional consequence of SIRT1 elevation in the nucleus may be inhibition of c-Jun activity. The expression of 21 genes was altered, including downregulation of PTGS2, and this correlated with reduced protein levels of cyclooxygenase-2 (COX-2). Overall, efficacious induction of G0/G1 cell cycle arrest at low concentrations, and induction of apoptosis at higher concentrations are interesting 4HWE-mediated phenomena that are accompanied by a complex array of molecular events. CONCLUSION: Considering the worldwide prevalence of colon cancer, and the unique mode of action mediated by 4HWE, it is reasonable to investigate additional mechanistic details and the potential utility of this compound. PMID- 27006101 TI - Virosome engineering of colloidal particles and surfaces: bioinspired fusion to supported lipid layers. AB - Immunostimulating reconstituted influenza virosomes (IRIVs) are liposomes with functional viral envelope glycoproteins: influenza virus hemagglutinin (HA) and neuraminidase intercalated in the phospholipid bilayer. Here we address the fusion of IRIVs to artificial supported lipid membranes assembled on polyelectrolyte multilayers on both colloidal particles and planar substrates. The R18 assay is used to prove the IRIV fusion in dependence of pH, temperature and HA concentration. IRIVs display a pH-dependent fusion mechanism, fusing at low pH in analogy to the influenza virus. The pH dependence is confirmed by the Quartz Crystal Microbalance technique. Atomic Force Microscopy imaging shows that at low pH virosomes are integrated in the supported membrane displaying flattened features and a reduced vertical thickness. Virosome fusion offers a new strategy for transferring biological functions on artificial supported membranes with potential applications in targeted delivery and sensing. PMID- 27006102 TI - Quality of red cells after combination of prion reduction and treatment with the intercept system for pathogen inactivation. AB - BACKGROUND AND OBJECTIVES: The pathogen inactivation (PI) INTERCEPT Blood System for Red Blood Cells utilises amustaline (S-303) to inactivate a broad range of pathogens in red cell concentrates (RCC). The aim of this study was to investigate the effect on red cell quality of INTERCEPT treatment with and without prion reduction. METHODS/MATERIALS: Five pools of five RCC each were prepared. These were split and treated as follows: (i) stored at 2-6 degrees C for 18 h, (ii) stored at 18-24 degrees C for 18 h, (iii) PI-treated, (iv) PI treated then prion reduced and (v) prion reduced then PI-treated. Prior to storage, PI-treated RCC underwent an exchange step to remove S-303 and other breakdown products. Components were tested throughout 35 days of storage for in vitro parameters of red cell quality. RESULTS: All RCC met specification for volume and haemoglobin content. Haemolysis, microvesicle formation, supernatant potassium and deformability were lower and ATP levels higher in PI-treated units when compared with control units. The effect of prion reduction in addition to PI treatment was minimal in all parameters tested except haemolysis, which was increased in units prion-reduced after being PI-treated. CONCLUSION: The PI treatment process did not increase red cell haemolysis or decrease ATP levels over storage. The lower haemolysis and supernatant potassium levels in treated RCC compared with control RCC were attributed to the exchange step. The effects of combining PI treatment and prion reduction were not more than additive when prion reduction precedes PI treatment. PMID- 27006103 TI - Maternal and placental risk factors for light-for-gestational-age births. AB - AIM: We conducted a cross-sectional study to investigate risk factors for births of light-for-gestational-age (LGA) infants. METHODS: A survey was conducted at the Department of Obstetrics and Gynecology at Sapporo Medical University Hospital in Sapporo, Japan from 2013 to 2014. LGA and appropriate for gestational age (AGA) are defined as having a birthweight below the 10th percentile and between the 10th percentile and 90th percentile for gestational age at birth in the population standard of gestational age, sex, and parity, respectively. An odds ratio (OR) and its 95% confidence interval (95%CI) for LGA were calculated by analysis using the logistic regression model. RESULTS: In total, 307 inpatients (94.2%) participated in the study out of 326 consecutive post-partum inpatients. Among them, 37 infants and 237 infants were classified into the LGA and AGA groups, respectively. As a result of multivariable analysis, prevalence of gestational hypertension (OR = 8.96, 95%CI 1.81-44.35) and the presence of placental infarction (OR = 9.65, 95%CI 1.76-53.01) were significantly associated with an increased risk of LGA. Placentas weighing 510-603 g and >=604 g were significantly associated with reduced risk of LGA (OR = 0.04, 95%CI 0.01-0.29 and OR = 0.03, 95%CI 0.01-0.32, respectively), and higher placental weights were significantly observed in the trend for reduced LGA risk (P for trend < 0.001). CONCLUSION: We found that the prevalence of gestational hypertension, lower placental weight, and the presence of placental infarctions were all independently associated with the risk of LGA. Placental abnormalities may be etiologically important for LGA risk, though further research is necessary. PMID- 27006105 TI - Ultrafast excited state dynamics of iridium(III) complexes and their changes upon immobilisation onto titanium dioxide layers. AB - Time-resolved spectroscopy was applied to investigate the excited state dynamics of two heteroleptic Ir(III) complexes with the general formula [Ir(C^N)2(N^N)](+), where C^N and N^N represent different cyclometalating and diimine ligands, respectively. The excited state relaxation is influenced by the ligand substitution as well as the light polarisation. Vibrational relaxation occurs in the sub-ps timescale and interligand charge transfer results in polarisation dependent signal dynamics with a time constant of about 30 ps. Electron injection from the iridium dye to TiO2 is analysed with respect to potential applications in solar energy conversion. PMID- 27006104 TI - Correlation Between Arthroscopy Simulator and Video Game Performance: A Cross Sectional Study of 30 Volunteers Comparing 2- and 3-Dimensional Video Games. AB - PURPOSE: To investigate the association between arthroscopy simulator performance and video game skills. METHODS: This study compared the performances of 30 volunteers without experience performing arthroscopies in 3 different tasks of a validated virtual reality knee arthroscopy simulator with the video game experience using a questionnaire and actual performances in 5 different 2- and 3 dimensional (D) video games of varying genres on 2 different platforms. RESULTS: Positive correlations between knee arthroscopy simulator and video game performances (rho = 0.63, P < .001) as well as experiences (rho = 0.50, P = .005) were found. The strongest correlations were found for the task of catching (hooking) 6 foreign bodies (virtual rings; "triangulation") and the dribbling performance in a sports game and a first-person shooter game, as well as the meniscus resection and a tile-matching puzzle game (all rho >= 0.60, P < .001). No correlations were found for any of the knee arthroscopy simulator tasks and a strategy game. CONCLUSIONS: Although knee arthroscopy performances do not correlate with 2-D strategy video game skills, they show a correlation with 2-D tile-matching puzzle games only for easier tasks with a rather limited focus, and highly correlate with 3-D sports and first-person shooter video games. These findings show that experienced and good 3-D gamers are better arthroscopists than nonexperienced and poor 3-D gamers. LEVEL OF EVIDENCE: Level II, observational cross-sectional study. PMID- 27006106 TI - Sporadic Burkitt's lymphoma/acute B-cell leukaemia presenting with progressive proptosis and orbital mass in a child. AB - Burkitt's lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is found predominantly in children, with the highest incidence occurring in Africa. The sporadic form occurs in non-endemic areas and typically involves the ileo caecum and the bowel, whereas orbital and paranasal sinus involvement is rare. Here, we present an unusual case of sporadic BL in a Caucasian male child with rapidly progressive painful proptosis of the right eye. Magnetic resonance imaging showed an oval-shaped, extraconal mass in the supero-lateral part of the right orbit that deformed and dislocated the eyeball antero-inferiorly. The patient underwent anterior orbitotomy, and a biopsy of the excised tissue revealed a starry-sky appearance characteristic of BL. Postoperative aggressive chemotherapy was initiated with a good response after one week. PMID- 27006107 TI - Identification and in vivo evaluation of a fluorine-18 rolipram analogue, [(18) F]MNI-617, as a radioligand for PDE4 imaging in mammalian brain. AB - Phosphodiesterase (PDE) 4 is the most prevalent PDE in the central nervous system (CNS) and catalyzes hydrolysis of intracellular cAMP, a secondary messenger. By therapeutic inhibition of PDE4, intracellular cAMP levels can be stabilized, and the symptoms of psychiatric and neurodegenerative disorders including depression, memory loss and Parkinson's disease can be ameliorated. Radiotracers targeting PDE4 can be used to study PDE4 density and function, and evaluate new PDE4 therapeutics, in vivo in a non-invasive way, as has been shown using the carbon 11 labeled PDE4 inhibitor R-(-)-rolipram. Herein we describe a small series of rolipram analogs that contain fluoro- or iodo-substituents that could be used as fluorine-18 PET or iodine-123 SPECT PDE4 radiotracers. This series was evaluated with an in vitro binding assay and a 4-(fluoromethyl) derivative of rolipram, MNI 617, was identified, with a five-fold increase in affinity for PDE4 (Kd = 0.26 nM) over R-(-)-rolipram (Kd = 1.6 nM). A deutero-analogue d2 -[(18) F]MNI-617 was radiolabeled and produced in 23% yield with high (>5 Ci/umol) specific activity and evaluated in non-human primate, where it rapidly entered the brain, with SUVs between 4 and 5, and with a distribution pattern consistent with that of PDE4. PMID- 27006108 TI - MECHANISMS IN ENDOCRINOLOGY: Hypothalamic inflammation and nutrition. AB - Selected subpopulations of hypothalamic neurons play important roles in the regulation of whole body energy homeostasis. Studies have shown that the saturated fats present in large amounts in western diets can activate an inflammatory response in the hypothalamus, affecting the capacity of such neurons to respond appropriately to satiety and adipostatic signals. In the first part of this review, we will explore the mechanisms behind saturated fatty acid-induced hypothalamic dysfunction. Next, we will present and discuss recent studies that have identified the mechanisms that mediate some of the anti-inflammatory actions of unsaturated fatty acids in the hypothalamus and the potential for exploring these mechanisms to prevent or treat obesity. PMID- 27006111 TI - Ion-Exclusion High-Performance Liquid Chromatography of Aliphatic Organic Acids Using a Surfactant-Modified C18 Column. AB - Ion exclusion chromatography (IELC) of short chain aliphatic carboxylic acids is normally done using a cation exchange column under standard HPLC conditions but not in the ultra-HPLC (UHPLC) mode. A novel IELC method for the separation of this class of carboxylic acids by either HPLC or UHPLC utilizing a C18 column dynamically modified with sodium dodecyl sulfate has been developed. The sample capacity is estimated to be near 10 mM for a 20 uL injection or 0.2 umol using a 150 * 4.6 mm column. The optimum mobile phase determined for three standard mixtures of organic acids is 1.84 mM sulfuric acid at pH 2.43 and a flow rate of 0.6 mL/min. Under optimized conditions, a HPLC separation of four aliphatic carboxylic acids such as tartaric, malonic, lactic and acetic can be achieved in under 4 min and in <2 min in the UHPLC mode at 2.1 mL/min. A variety of fruit juice and soft drink samples are analyzed. Stability of the column as measured by the retention order of maleic and fumaric acid is estimated to be ~4,000 column volumes using HPLC and 600 by UHPLC. Reproducible chromatograms are achieved over at least a 2-month period. This study shows that the utility of a C18 column can be easily extended when needed to IELC under either standard or UHPLC conditions. PMID- 27006109 TI - Global cardiac risk assessment in the Registry Of Pregnancy And Cardiac disease: results of a registry from the European Society of Cardiology. AB - AIMS: To validate the modified World Health Organization (mWHO) risk classification in advanced and emerging countries, and to identify additional risk factors for cardiac events during pregnancy. METHODS AND RESULTS: The ongoing prospective worldwide Registry Of Pregnancy And Cardiac disease (ROPAC) included 2742 pregnant women (mean age +/- standard deviation, 29.2 +/- 5.5 years) with established cardiac disease: 1827 from advanced countries and 915 from emerging countries. In patients from advanced countries, congenital heart disease was the most prevalent diagnosis (70%) while in emerging countries valvular heart disease was more common (55%). A cardiac event occurred in 566 patients (20.6%) during pregnancy: 234 (12.8%) in advanced countries and 332 (36.3%) in emerging countries. The mWHO classification had a moderate performance to discriminate between women with and without cardiac events (c-statistic 0.711 and 95% confidence interval (CI) 0.686-0.735). However, its performance in advanced countries (0.726) was better than in emerging countries (0.633). The best performance was found in patients with acquired heart disease from developed countries (0.712). Pre-pregnancy signs of heart failure and, in advanced countries, atrial fibrillation and no previous cardiac intervention added prognostic value to the mWHO classification, with a c-statistic of 0.751 (95% CI 0.715-0.786) in advanced countries and of 0.724 (95% CI 0.691-0.758) in emerging countries. CONCLUSION: The mWHO risk classification is a useful tool for predicting cardiac events during pregnancy in women with established cardiac disease in advanced countries, but seems less effective in emerging countries. Data on pre-pregnancy cardiac condition including signs of heart failure and atrial fibrillation, may help to improve preconception counselling in advanced and emerging countries. PMID- 27006112 TI - Impact of structure space continuity on protein fold classification. AB - Protein structure classification hierarchically clusters domain structures based on structure and/or sequence similarities and plays important roles in the study of protein structure-function relationship and protein evolution. Among many classifications, SCOP and CATH are widely viewed as the gold standards. Fold classification is of special interest because this is the lowest level of classification that does not depend on protein sequence similarity. The current fold classifications such as those in SCOP and CATH are controversial because they implicitly assume that folds are discrete islands in the structure space, whereas increasing evidence suggests significant similarities among folds and supports a continuous fold space. Although this problem is widely recognized, its impact on fold classification has not been quantitatively evaluated. Here we develop a likelihood method to classify a domain into the existing folds of CATH or SCOP using both query-fold structure similarities and within-fold structure heterogeneities. The new classification differs from the original classification for 3.4-12% of domains, depending on factors such as the structure similarity score and original classification scheme used. Because these factors differ for different biological purposes, our results indicate that the importance of considering structure space continuity in fold classification depends on the specific question asked. PMID- 27006114 TI - The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and is essential for reproduction. AB - Ca(2+) influx triggers sperm capacitation; however, the underlying regulatory mechanisms remain incompletely understood. Here, we show that CNNM4, a Mg(2+) transporter, is required for Ca(2+) influx during capacitation. We find that Cnnm4-deficient male mice are almost infertile because of sperm dysfunction. Motion analyses show that hyperactivation, a qualitative change in the mode of sperm motility during capacitation, is abrogated in Cnnm4-deficient sperm. In contrast, tyrosine phosphorylation of flagellar proteins, a hallmark of capacitation, is excessively augmented. These seemingly paradoxical phenotypes of Cnnm4-deficient sperm are very similar to those of sperm lacking a functional cation channel of sperm (CatSper) channel, which plays an essential role in Ca(2+) influx during sperm capacitation. Ca(2+) imaging analyses demonstrate that Ca(2+) influx is perturbed in Cnnm4-deficient sperm, and forced Ca(2+) entry into these sperm normalizes the level of tyrosine phosphorylation. Furthermore, we confirm the importance of CNNM4 in sperm by generating germ-cell-specific Cnnm4 deficient mice. These results suggest a new role of CNNM4 in sperm Ca(2+) homeostasis. PMID- 27006113 TI - Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers. AB - Near-misses in gambling games are losing events that come close to a win. Near misses were previously shown to recruit reward-related brain regions including the ventral striatum, and to invigorate gambling behavior, supposedly by fostering an illusion of control. Given that pathological gamblers are particularly vulnerable to such cognitive illusions, their persistent gambling behavior might result from an amplified striatal sensitivity to near-misses. In addition, animal studies have shown that behavioral responses to near-miss-like events are sensitive to dopamine, but this dopaminergic influence has not been tested in humans. To investigate these hypotheses, we recruited 22 pathological gamblers and 22 healthy controls who played a slot machine task delivering wins, near-misses and full-misses, inside an fMRI scanner. Each participant played the task twice, once under placebo and once under a dopamine D2 receptor antagonist (sulpiride 400 mg), in a double-blind, counter-balanced design. Participants were asked about their motivation to continue gambling throughout the task. Across all participants, near-misses elicited higher motivation to continue gambling and increased striatal responses compared with full-misses. Crucially, pathological gamblers showed amplified striatal responses to near-misses compared with controls. These group differences were not observed following win outcomes. In contrast to our hypothesis, sulpiride did not induce any reliable modulation of brain responses to near-misses. Together, our results demonstrate that pathological gamblers have amplified brain responses to near-misses, which likely contribute to their persistent gambling behavior. However, there is no evidence that these responses are influenced by dopamine. These results have implications for treatment and gambling regulation. PMID- 27006115 TI - Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage. AB - Oligodendrocyte precursor cells (OPCs) undergo a series of energy-consuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and ethidium bromide uptake or increase of 2-NBDG uptake rate is correlated with intracellular Ca(2+) elevation in OPCs, indicating a Ca(2+)-dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43, also known as GJA1) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting on OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which might pave a new way for energy metabolism-directed oligodendroglial-targeted therapies. PMID- 27006117 TI - The paracaspase MALT1 cleaves the LUBAC subunit HOIL1 during antigen receptor signaling. AB - Antigen-receptor-mediated activation of lymphocytes relies on a signalosome comprising CARMA1 (also known as CARD11), BCL10 and MALT1 (the CBM complex). The CBM activates nuclear factor kappaB (NF-kappaB) transcription factors by recruiting the 'linear ubiquitin assembly complex' (LUBAC), and unleashes MALT1 paracaspase activity. Although MALT1 enzyme shapes NF-kappaB signaling, lymphocyte activation and contributes to lymphoma growth, the identity of its substrates continues to be elucidated. Here, we report that the LUBAC subunit HOIL1 (also known as RBCK1) is cleaved by MALT1 following antigen receptor engagement. HOIL1 is also constitutively processed in the 'activated B-cell-like' (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), which exhibits aberrant MALT1 activity. We further show that the overexpression of MALT1-insensitive HOIL1 mitigates T-cell-receptor-mediated NF-kappaB activation and subsequent cytokine production in lymphocytes. Thus, our results unveil HOIL1 as a negative regulator of lymphocyte activation cleaved by MALT1. This cleavage could therefore constitute an appealing therapeutic target for modulating immune responses. PMID- 27006116 TI - Complement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation. AB - Complement activation has long been associated with inflammation, primarily due to the elaboration of the complement anaphylotoxins C5a and C3a. In this work, we demonstrate that the phagocytosis of complement-opsonized particles promotes host inflammatory responses by a new mechanism that depends on the terminal complement components (C5b-C9). We demonstrate that during the phagocytosis of complement opsonized particles, the membrane attack complex (MAC) of complement can be transferred from the activating particle to the macrophage plasma membrane by a 'bystander' mechanism. This MAC-mediated bystander damage initiates NLRP3 inflammasome activation, resulting in caspase-1 activation and IL-1beta and IL-18 secretion. Inflammasome activation is not induced when macrophages phagocytize unopsonized particles or particles opsonized with serum deficient in one of the terminal complement components. The secretion of IL-1beta and IL-18 by macrophages depends on NLRP3, ASC (also known as PYCARD) and caspase-1, as macrophages deficient in any one of these components fail to secrete these cytokines following phagocytosis. The phagocytosis of complement-opsonized particles increases leukocyte recruitment and promotes T helper 17 cell (TH17) biasing. These findings reveal a new mechanism by which complement promotes inflammation and regulates innate and adaptive immunity. PMID- 27006118 TI - An Approach to Working Up Cases of Embolic Stroke of Undetermined Source. AB - BACKGROUND: From a therapeutic viewpoint, it is important to differentiate the underlying causes of embolism in patients with cryptogenic stroke, such as aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. We investigated the clinical and radiological characteristics of these 3 common causes of cryptogenic embolism to develop models for decision making in etiologic workups. METHODS AND RESULTS: A total of 321 consecutive patients with acute infarcts from cryptogenic embolism were included. Patients were divided into 3 groups-aortic arch atheroma (n=40), patent foramen ovale (n=153), and paroxysmal atrial fibrillation (n=128)-based on extensive cardiologic workups. We used a multinomial logistic regression analysis to detect the clinical and diffusion weighted imaging factors associated with the probability of aortic arch atheroma, patent foramen ovale, and paroxysmal atrial fibrillation. Clinical and radiological features differed among the groups. The patent foramen ovale group had a healthy vascular risk factor profile and showed posterior circulation involvement compared with other groups (P<0.01). In contrast, paroxysmal atrial fibrillation-related strokes had higher initial National Institutes of Health Stroke Scale (NIHSS) scores and larger lesions than the other groups (P<0.001). The aortic arch atheroma group had clinical features similar to those of the paroxysmal atrial fibrillation group but showed small lesions scattered in multiple vascular territories (P<0.001). Multivariate regression analysis revealed that age, initial NIHSS score, lesion size (>=20 mm), multiple (>=3) lesions, and involvement of posterior circulation or multiple vascular territories differentiated the 3 groups (pseudo, R(2)=0.656). The prediction ability of this model was validated in the external validation cohort (n=117, area under the curve 0.78). CONCLUSIONS: Our data indicate that patients with cryptogenic embolic stroke show distinct clinical and radiological features depending on the underlying causes. PMID- 27006123 TI - Max Scheler's theory of the hierarchy of values and emotions and its relevance to current psychopathology. AB - The philosopher Max Scheler (1874-1928) set out a hierarchical theory of values and emotions in the early twentieth century. This inspired Kurt Schneider to distinguish two sorts of depressive illness, each conforming to a Storung (disorder) in different levels of Scheler's hierarchy. No other psychopathologist, except Stanghellini, gave the matter much attention. I believe that Scheler's theory is a rich source of insight into psychopathology, general and neuropsychiatric. I therefore give an account of Scheler's scheme, review its extant applications (Schneider's, Stanghellini's), and present suggestions as to its continuing potential relevance in a wide range of psychopathological conditions. PMID- 27006119 TI - Coronary CT Angiography Versus Standard Emergency Department Evaluation for Acute Chest Pain and Diabetic Patients: Is There Benefit With Early Coronary CT Angiography? Results of the Randomized Comparative Effectiveness ROMICAT II Trial. AB - BACKGROUND: Cardiac computed tomography angiography (CCTA) reduces emergency department length of stay compared with standard evaluation in patients with low- and intermediate-risk acute chest pain. Whether diabetic patients have similar benefits is unknown. METHODS AND RESULTS: In this prespecified analysis of the Rule Out Myocardial Ischemia/Infarction by Computer Assisted Tomography (ROMICAT II) multicenter trial, we randomized 1000 patients (17% diabetic) with symptoms suggestive of acute coronary syndrome to CCTA or standard evaluation. The rate of acute coronary syndrome was 8% in both diabetic and nondiabetic patients (P=1.0). Length of stay was unaffected by the CCTA strategy for diabetic patients (23.9 versus 27.2 hours, P=0.86) but was reduced for nondiabetic patients compared with standard evaluation (8.4 versus 26.5 hours, P<0.0001; P interaction=0.004). CCTA resulted in 3-fold more direct emergency department discharge in both groups (each P<=0.0001, P interaction=0.27). No difference in hospital admissions was seen between the 2 strategies in diabetic and nondiabetic patients (P interaction=0.09). Both groups had more downstream testing and higher radiation doses with CCTA, but these were highest in diabetic patients (all P interaction<=0.04). Diabetic patients had fewer normal CCTAs than nondiabetic patients (32% versus 50%, P=0.003) and similar normalcy rates with standard evaluation (P=0.70). Notably, 66% of diabetic patients had no or mild stenosis by CCTA with short length of stay comparable to that of nondiabetic patients (P=0.34), whereas those with >50% stenosis had a high prevalence of acute coronary syndrome, invasive coronary angiography, and revascularization. CONCLUSIONS: Knowledge of coronary anatomy with CCTA is beneficial for diabetic patients and can discriminate between lower risk patients with no or little coronary artery disease who can be discharged immediately and higher risk patients with moderate to severe disease who warrant further workup. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01084239. PMID- 27006124 TI - Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus, Including Cases with Obstructive Jaundice. AB - BACKGROUND: This study aimed to evaluate the short- and long-term outcomes of hepatectomy for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT), including cases with obstructive jaundice. METHODS: The study reviewed 42 HCC patients with BDTT, including six patients who needed preoperative biliary drainage due to obstructive jaundice, and 732 HCC patients without BDTT. The authors analyzed the impact of BDTT on the surgical outcomes and assessed the outcomes of hepatectomy for patients presenting with obstructive jaundice. RESULTS: The HCC patients with BDTT, almost all with stage 3 or 4 disease, had increased alpha-fetoprotein expression, larger tumors, and more portal vein invasion status. The survival of the HCC patients with BDTT was significantly inferior to that of the patients without BDTT (p = 0.0003). Survival did not differ significantly between the HCC patients with BDTT and those without BDTT when the two groups were matched by stage (p = 0.3366). The HCC patients with BDTT who presented with obstructive jaundice demonstrated outcomes similar to those for the HCC patients with BDTT who did not present with obstructive jaundice in terms of the overall survival rate (p = 0.5469). The perioperative outcomes for the HCC patients with BDTT did not depend on the presence or absence of preoperative jaundice. No patients in either BDTT group demonstrated 90-day mortality in this study. CONCLUSIONS: Hepatectomy should be considered for HCC patients with BDTT, even for patients with obstructive jaundice, because the surgical outcomes equivalent to those for HCC without BDTT can be achieved. PMID- 27006125 TI - Delayed Calcium Normalization After Presumed Curative Parathyroidectomy is Not Associated with the Development of Persistent or Recurrent Primary Hyperparathyroidism. AB - BACKGROUND: Following parathyroidectomy for primary hyperparathyroidism (pHPT), serum calcium levels typically normalize relatively quickly. The purpose of this study was to identify potential factors associated with delayed normalization of calcium levels despite meeting intraoperative parathyroid hormone (IOPTH) criteria and to determine whether this phenomenon is associated with higher rates of persistent pHPT. METHODS: This was a retrospective review of 554 patients who underwent parathyroidectomy for sporadic pHPT from January 2009 to July 2013. Patients who underwent presumed curative parathyroidectomy and had elevated POD0 calcium levels (>10.2 mg/dL) were matched 1:2 for age and gender to control patients with normal POD0 calcium levels. RESULTS: Of the 554 patients, 52 (9 %) had an elevated POD0 Ca (median 10.7, range 10.3-12.2). Compared with the control group, these patients had higher preoperative calcium (12 vs. 11.1, p < 0.001) and PTH (144 vs. 110 pg/mL, p = 0.004) levels and lower 25OH vitamin D levels (26 vs. 31 pg/mL; p = 0.024). Calcium normalization occurred in 64, 90, and 96 % of patients by postoperative days (POD) 1, 14, and 30, respectively. There was no difference in rates of single-gland disease or cure rates between the groups. CONCLUSIONS: After presumed curative parathyroidectomy, nearly 10 % of patients had transiently persistent hypercalcemia. Most of these patients had normal serum calcium levels within the first 2 weeks and did not have increased rates of persistent pHPT. Immediate postoperative calcium levels do not predict the presence of persistent pHPT, and these patients may not require more stringent follow-up. PMID- 27006126 TI - Interaction of Postoperative Morbidity and Receipt of Adjuvant Therapy on Long Term Survival After Resection for Gastric Adenocarcinoma: Results From the U.S. Gastric Cancer Collaborative. AB - BACKGROUND: Postoperative complications (POCs) can negatively impact survival after oncologic resection. POCs may also decrease the rate of adjuvant therapy completion. We evaluated the impact of complications on gastric cancer survival and analyzed the combined effect of complications and adjuvant therapy on survival. METHODS: We analyzed 824 patients from 7 institutions of the U.S. Gastric Cancer Collaborative who underwent curative resection for gastric adenocarcinoma between 2000 and 2012. POC were graded using the modified Clavien Dindo system. Survival probabilities were estimated using the method of Kaplan and Meier and analyzed using multivariate Cox regression. RESULTS: Median follow up was 35 months. The overall complication rate was 41 %. The 5-year overall survival (OS) and recurrence-free survival (RFS) of patients who experienced complications were 27 and 23 %, respectively, compared with 43 and 40 % in patients who did not have complications (p < 0.0001 for OS and RFS). On multivariate analysis, POC remained an independent predictor for decreased OS and RFS (HR 1.3, 95 % CI 1.1-1.6, p = 0.03 for OS; HR 1.3, 95 % CI 1.01-1.6, p = 0.03 for RFS). Patients who experienced POC were less likely to receive adjuvant therapy (OR 0.5, 95 % CI 0.3-0.7, p < 0.001). The interaction of complications and failure to receive adjuvant therapy significantly increased the hazard of death compared with patients who had neither complications nor adjuvant therapy (HR 2.3, 95 % CI 1.6-3.2, p < 0.001). CONCLUSIONS: Postoperative complications adversely affect long-term outcomes after gastrectomy for gastric cancer. Not receiving adjuvant therapy in the face of POC portends an especially poor prognosis following gastrectomy for gastric cancer. PMID- 27006127 TI - Skeletal Muscle Changes After Elective Colorectal Cancer Resection: A Longitudinal Study. AB - BACKGROUND: Muscle depletion is a poor prognostic indicator in colorectal cancer (CRC) patients, but there were no data assessing comparative temporal body composition changes following elective CRC surgery. We examined patient skeletal muscle index trajectories over time after surgery and determined factors that may contribute to those alterations. METHODS: Patients diagnosed with CRC undergoing elective surgical resection between 2006 and 2013 were included in this study. Image analysis of serial computed tomography (CT) scans was used to calculate lumbar skeletal muscle index (LSMI). A multilevel mixed-effect linear regression model was applied using STATA (version 12.0) using the xtmixed command to fit growth curve models (GCM) for LSMI and time. RESULTS: In 856 patients, a total of 2136 CT images were analyzed; 856 (38.2 %) were preoperative. A quadratic GCM with random intercept and random slope for patients' LSMI was identified that demonstrated laparoscopy produces a positive change on the LSMI curve [estimate = 0.17 cm(2)/m(2), standard error (SE) 0.06 cm(2)/m(2); p = 0.03], whereas Union for International Cancer Control (UICC) stage III + IV disease contributed to a negative curve change (estimate = -0.19 cm(2)/m(2), SE 0.09 cm(2)/m(2); p = 0.03). Older age (p < 0.01), female gender (p < 0.01), higher American Society of Anesthesiologists (ASA) score (p < 0.01), and altered systemic inflammatory response [SIR] (p = 0.03) were factors significantly associated with lower values of LSMI over time. CONCLUSION: In patients undergoing CRC surgery, laparoscopy and the absence of a significantly elevated SIR favored preservation and restoration of skeletal muscle, postoperatively. These emerging data may permit the development of new treatment protocols whereby monitoring and modification of body composition has therapeutic potential. PMID- 27006128 TI - Gastric outlet obstruction-A rare cause. PMID- 27006129 TI - Long-term time-lapse live imaging reveals extensive cell migration during annelid regeneration. AB - BACKGROUND: Time-lapse imaging has proven highly valuable for studying development, yielding data of much finer resolution than traditional "still-shot" studies and allowing direct examination of tissue and cell dynamics. A major challenge for time-lapse imaging of animals is keeping specimens immobile yet healthy for extended periods of time. Although this is often feasible for embryos, the difficulty of immobilizing typically motile juvenile and adult stages remains a persistent obstacle to time-lapse imaging of post-embryonic development. RESULTS: Here we describe a new method for long-duration time-lapse imaging of adults of the small freshwater annelid Pristina leidyi and use this method to investigate its regenerative processes. Specimens are immobilized with tetrodotoxin, resulting in irreversible paralysis yet apparently normal regeneration, and mounted in agarose surrounded by culture water or halocarbon oil, to prevent dehydration but allowing gas exchange. Using this method, worms can be imaged continuously and at high spatial-temporal resolution for up to 5 days, spanning the entire regeneration process. We performed a fine-scale analysis of regeneration growth rate and characterized cell migration dynamics during early regeneration. Our studies reveal the migration of several putative cell types, including one strongly resembling published descriptions of annelid neoblasts, a cell type suggested to be migratory based on "still-shot" studies and long hypothesized to be linked to regenerative success in annelids. CONCLUSIONS: Combining neurotoxin-based paralysis, live mounting techniques and a starvation-tolerant study system has allowed us to obtain the most extensive high resolution longitudinal recordings of full anterior and posterior regeneration in an invertebrate, and to detect and characterize several cell types undergoing extensive migration during this process. We expect the tetrodotoxin paralysis and time-lapse imaging methods presented here to be broadly useful in studying other animals and of particular value for studying post-embryonic development. PMID- 27006130 TI - The Use of Minipigs for Preclinical Safety Assessment by the Pharmaceutical Industry: Results of an IQ DruSafe Minipig Survey. AB - The use of minipigs in preclinical safety testing of pharmaceuticals is considered an alternative to the more traditional dog and nonhuman primate (NHP) nonrodent species. Substantial evidence exists to suggest that the anatomy, physiology, and biochemistry of minipigs are similar enough to humans to consider them as valid nonrodent models for pharmaceutical safety testing. Since the utilization of minipigs was last assessed over 5 years ago, the Preclinical Safety Leadership Group (DruSafe) of the International Consortium for Innovation and Quality in Pharmaceutical Development conducted this survey to provide an updated assessment of the utility, perceived value, and impediments to the use of minipigs in preclinical safety testing. Of the 32 participating members of DruSafe, 15 responded to the survey representing both large and small companies. Respondents indicated that the minipig has been utilized mostly for short-term safety assessment studies with dermal, oral, and parenteral routes of administration. Minipigs are widely accepted as appropriate models for cardiovascular assessments and have been used to a limited extent for reproductive toxicology testing. Overall responses indicated that safety testing for large molecules using this species is relatively low due to a lack of background data, reagents or biomarkers, concerns regarding immune system characterization and poor suitability for developmental toxicity assessments. Most companies utilized contract research organizations for definitive safety toxicity assessment studies. Conclusions of this survey indicate that minipig is an acceptable nonrodent species largely limited to studies using small molecules, primarily dermal products, and results are comparable to those reported 5 years ago. PMID- 27006132 TI - US areas with highest heart death rates have shifted from north east to south. PMID- 27006131 TI - Use of thermo-coagulation as an alternative treatment modality in a 'screen-and treat' programme of cervical screening in rural Malawi. AB - The incidence of cervical cancer in Malawi is the highest in the world and projected to increase in the absence of interventions. Although government policy supports screening using visual inspection with acetic acid (VIA), screening provision is limited due to lack of infrastructure, trained personnel, and the cost and availability of gas for cryotherapy. Recently, thermo-coagulation has been acknowledged as a safe and acceptable procedure suitable for low-resource settings. We introduced thermo-coagulation for treatment of VIA-positive lesions as an alternative to cryotherapy within a cervical screening service based on VIA, coupled with appropriate, sustainable pathways of care for women with high grade lesions and cancers. Detailed planning was undertaken for VIA clinics, and approvals were obtained from the Ministry of Health, Regional and Village Chiefs. Educational resources were developed. Thermo-coagulators were introduced into hospital and health centre settings, with theoretical and practical training in safe use and maintenance of equipment. A total of 7,088 previously unscreened women attended VIA clinics between October 2013 and March 2015. Screening clinics were held daily in the hospital and weekly in the health centres. Overall, VIA positivity was 6.1%. Almost 90% received same day treatment in the hospital setting, and 3- to 6-month cure rates of more than 90% are observed. Thermo coagulation proved feasible and acceptable in this setting. Effective implementation requires comprehensive training and provider support, ongoing competency assessment, quality assurance and improvement audit. Thermo coagulation offers an effective alternative to cryotherapy and encouraged VIA screening of many more women. PMID- 27006133 TI - Nanoparticles and radiotracers: advances toward radionanomedicine. AB - In this study, we cover the convergence of radiochemistry for imaging and therapy with advances in nanoparticle (NP) design for biomedical applications. We first explore NP properties relevant for therapy and theranostics and emphasize the need for biocompatibility. We then explore radionuclide-imaging modalities such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and Cerenkov luminescence (CL) with examples utilizing radiolabeled NP for imaging. PET and SPECT have served as diagnostic workhorses in the clinic, while preclinical NP design examples of multimodal imaging with radiotracers show promise in imaging and therapy. CL expands the types of radionuclides beyond PET and SPECT tracers to include high-energy electrons (beta- ) for imaging purposes. These advances in radionanomedicine will be discussed, showing the potential for radiolabeled NPs as theranostic agents. WIREs Nanomed Nanobiotechnol 2016, 8:872 890. doi: 10.1002/wnan.1402 For further resources related to this article, please visit the WIREs website. PMID- 27006135 TI - Distal radius fractures-Design of locking mechanism in plate system and recent surgical procedures. AB - Recently, many studies have emphasized the importance of the comprehension of detailed functional anatomy of the distal forearm and wrist joint, and their biomechanics. A significant contribution which yields good functional outcomes of surgical treatment was the development of the locking plate technology; this technology has facilitated the improvement of the surgical technique for the fixation of fractures. This article reviews the locking mechanism and design of the fixation screws and plate, and the details of the surgical technique including the double-tired subchondral support procedure as it is applied to common fractures. Arthroscopic-assisted surgical procedures can be used to reduce the intra-articular fracture fragments after realignment of the distal radius with the locking plate. This technique is also useful at the time of fixation to assess soft tissue injury. The combination of arthroscopic-assisted reduction and locking plate fixation is now indicated for AO type C2 and C3 intra-articular comminuted fractures. PMID- 27006134 TI - Consumers' and workers' perspectives about consumer-directed services in the United States. AB - BACKGROUND: Consumer direction is a service delivery model that shifts decision making from agencies to the individuals they serve. Using government funding, consumers hire, supervise, and schedule their own staff and maintain control over the delivery of their services. OBJECTIVE: This study sought to understand the process of consumer direction as well as the experiences and perspectives of both the consumers and employees. The study also sought to better understand if and how consumer direction allows the consumer to direct his or her life, the impact consumer direction may have on the individual's health and health care, and how employment in consumer directed programs impacts the workers providing direct care services. METHOD: This qualitative study included interviews with consumers (N = 20) and workers (N = 15) in Virginia, a southern state in the US. Semi structured phone interviews were conducted by one member of the research team and transcribed and coded for themes by the research team using grounded theory methodology. RESULTS: Consumers reported greater control over their services and increased access to health care, compared to what they previously received with traditional services. Conversely, consumers reported challenges in managing their staff and fulfilling the role of an employer. Employees reported a lack of training prior to starting their jobs, as well as an inability to live off on low hourly wages. Still, the majority of employees reported job satisfaction and fulfillment. CONCLUSION: Policymakers should expand and strengthen the consumer directed program. PMID- 27006136 TI - Perceived Physical Activity Decline as a Mediator in the Relationship Between Pain Catastrophizing, Disability, and Quality of Life in Patients with Painful Diabetic Neuropathy. AB - BACKGROUND: To fully understand the burden of painful diabetic neuropathy (PDN), we investigated the relationship of pain catastrophizing with disability and quality of life in patients with PDN. Furthermore, we studied the mediating roles of physical activity and/or decline in physical activity. METHODS: This questionnaire-based cross-sectional study included 154 patients with PDN. Linear regression analyses, adjusted for age, gender, pain intensity, and insulin treatment, were performed to assess the association of pain catastrophizing (Pain Catastrophizing Scale [PCS]) with the outcome variables disability (Pain Disability Index [PDI]) and quality of life (Norfolk Quality of Life Questionnaire Diabetic Neuropathy Version [QOL-DN]). The mediating roles of actual physical activity (Physical Activity Rating Scale [PARS]) and perceived Physical Activity Decline (PAD) were assessed using mediation analyses according to Baron and Kenny. RESULTS: This study included 154 patients (62% male). Mean age was 65.7 years (SD = 6.6). PCS (M = 20.3, SD = 13.1) was significantly associated with PDI (M = 32.4, SD = 17.0; R2 = 0.356, P < 0.001), QOL-DN (M = 52.6, SD = 26.1; R2 = 0.437, P < 0.001), and PAD (M = 7.4, SD = 5.7; R2 = 0.087, P = 0.045). PAD acted as a partial mediator in the associations of PCS with PDI and QOL-DN, respectively. There was no association of PCS with PARS. CONCLUSIONS: Pain catastrophizing was associated with increased disability and decreased quality of life in patients with PDN. Also, it was associated with a perceived decline in physical activity, which had a mediating role in the association between catastrophizing and disability and quality of life, respectively. This study emphasizes the role of catastrophic thinking about pain and the experienced loss in daily activities due to PDN. PMID- 27006137 TI - [Acceptability and quality of abdominal ultrasound studies requested by medical professionals]. AB - OBJECTIVE: To evaluate the acceptability/quality of abdominal ultrasound studies requested by primary care physicians in Barcelona; to develop ultrasound guidelines and assess their impact on acceptability. METHODS: DESIGN: 2-phase study, one retrospective, descriptive phase evaluating the acceptability/quality of requests (pre-intervention phase) and another to assess the impact of guidelines on acceptability/quality (post-intervention phase). SUBJECTS: Requests for ultrasound studies from January-June 2010 from 10 primary care centers and the same number of requests from the same centers after the intervention. VARIABLES: Pre-intervention phase: reason for consultation and request; presence of diagnostic orientation; results of ultrasound; acceptability/quality of the request. INTERVENTION: design guidelines using the nominal group technique, dissemination of guidelines in the same centers. Post-intervention phase: three months after dissemination analyze the same number of requests assessing the same variables included in the pre-intervention phase. RESULTS: Pre-intervention phase: 1,063 requests, 52.4% women, mean age 52+/-16years (range 11-94). Post intervention phase: 1,060 requests, 57.6% women, mean age 54+/-17years (range 6 91). Main reasons for requests: abdominal pain/discomfort 38.3% (pre intervention) and 43.1% (post-intervention). Diagnostic orientation in 14.5% (pre intervention) and 40.8% (post-intervention). Normal ultrasound results in 46.0% (pre-intervention) and 42.3% (post-intervention). Good quality of requests in 42.7% (pre-intervention) and 46.5% (post-intervention). Acceptability of ultrasound: 70.5% (pre-intervention) and 94.1% (post-intervention). The better the quality of the request, the better the acceptability of the studies and the greater the number of pathological conditions identified. CONCLUSIONS: Guidelines for ultrasound improve the quality of requests, diagnostic orientation and acceptability of the studies. PMID- 27006139 TI - Attitudes towards family formation in cohabiting and single childless women in their mid- to late thirties. AB - This study aimed to explore attitudes towards family formation in single or cohabiting childless women of advanced age. The design comprised semi-structured qualitative interviews of 20 women aged 34-39 years attending the Fertility Assessment and Counselling Clinic, Rigshospitalet, Copenhagen. A sample of 10 single women and 10 cohabiting women was chosen with equal distribution of postgraduate education length. Data were analysed using content analysis following the method of Graneheim and Lundman and consolidated criteria for reporting qualitative research (COREQ). The general attitude towards family formation was characterized by a fear of the consequences of choosing motherhood on one hand, and a 'ticking biological clock' and a wish to establish a nuclear family on the other. The women idealized the perception of perfect mothering in terms of uncompromising expectations of child rearing and showed an increasing awareness of solo motherhood as a possible solution to advanced age, the wish of a child and single status compared to earlier studies. Our study contributes to knowledge and understanding of personal considerations related to childbearing in nullipara women in their mid- to late 30s and may be useful in a fertility assessment and counselling setting. PMID- 27006140 TI - [History of the craniotomy]. AB - Craniotomy can be defined as the neurosurgical procedure aimed at achieving a wide cranial opening with the final purpose of performing a surgical therapeutic manoeuvre within the intracranial space. The current surgical technique for craniotomy is the final result of the development of the procedure since its introduction at the end of the 19th century. The very first wide cranial approach was introduced in 1889 by Wagner, and described as a 'temporary cranial resection'. This procedure could be named today as 'osteoplastic craniotomy with pedicle bone flap'. The final result of the procedural development of the craniotomy is the 'osteoplastic craniotomy with free bone flap', used widely around the world. In this paper, we review the historic evolution of craniotomy from a technical perspective. PMID- 27006138 TI - Dirhodium(II)-Catalyzed Annulation of Enoldiazoacetamides with alpha Diazoketones: An Efficient and Highly Selective Approach to Fused and Bridged Ring Systems. AB - A dirhodium(II)-catalyzed annulation reaction between two structurally different diazocarbonyl compounds furnishes the donor-acceptor cyclopropane-fused benzoxa[3.2.1]octane scaffold with excellent chemo-, regio-, and diastereoselectivity under exceptionally mild conditions. The composite transformation occurs by [3+2]-cycloaddition between donor-acceptor cyclopropenes generated from enoldiazoacetamides and carbonyl ylides formed from intramolecular carbene-carbonyl cyclization in one pot with one catalyst. The annulation products can be readily transformed into benzoxa[3.3.1]nonane and hexahydronaphthofuran derivatives with exact stereocontrol. This method allows the efficient construction of three fused and bridged ring systems, all of which are important skeletons of numerous biologically active natural products. PMID- 27006141 TI - Experience with "Fast track" postoperative care after deep brain stimulation surgery. AB - BACKGROUND: A 24-h-stay in the post-anesthesia care unit (PACU) is a common postoperative procedure after deep brain stimulation surgery (DBS). OBJECTIVE: We evaluated the impact of a fast-track (FT) postoperative care protocol. METHODS: An analysis was performed on all patients who underwent DBS in 2 periods: 2006, overnight monitored care (OMC group), and 2007-2013, FT care (FT group). RESULTS: The study included 19 patients in OMC and 95 patients in FT. Intraoperative complications occurred in 26.3% patients in OMC vs. 35.8% in FT. Post operatively, one patient in OMC developed hemiparesis, and agitation in 2 patients. In FT, two patients with intraoperative hemiparesis were transferred to the ICU. While on the ward, 3 patients from the FT developed hemiparesis, two of them 48h after the procedure. Thirty eight percent of FT had an MRI scan, while the remaining 62% and all patients of OMC had a CT-scan performed on their transfer to the ward. One patient in OMC had a subthalamic hematoma. Two patients in FT had a pallidal hematoma, and 3 a bleeding along the electrode. CONCLUSIONS: A FT discharge protocol is a safe postoperative care after DBS. There are a small percentage of complications after DBS, which mainly occur within the first 6h. PMID- 27006143 TI - TRH injected into the nucleus accumbens shell releases dopamine and reduces feeding motivation in rats. AB - The thyrotropin-releasing hormone (TRH), an anorexigenic factor that reduces food intake in food-restricted animals, may be involved in motivation for food. Injected centrally, TRH impairs acquisition of food-rewarded behavior. Through the TRH-R1 receptors, TRH injected in the nucleus accumbens increases dopamine content-perhaps the mechanism by which the peptide modulates food motivation. This, however, is still to be demonstrated. We sought to evaluate dopamine release by microdialysis after a TRH injection into the nucleus accumbens shell in free-moving fasted rats. In addition, we assessed dopamine content and turnover by HPLC and the relationship with the motivation for food by analyzing the performance of rats during a progressive-ratio (PR) operant-conditioning test. Finally, we determined serum leptin and triiodothyronine (T3) levels in order to evaluate the animals' metabolic response to food restriction and the impact of intra-accumbal TRH administration on circulating hormones. Intra accumbal injections of TRH reduced food intake in food-restricted rats-compared to counterparts treated with saline-, without further decreasing T3 or leptin levels, which dropped due to their dietary regime. TRH-injected rats had lower breaking points on the PR schedule, which indicated lower motivation to eat. Accordingly, compared to saline-treated animals, dopamine release and turnover increased in the nucleus accumbens of TRH-injected rats, a finding that suggests a relationship between motivation for food and TRH-induced release of dopamine. PMID- 27006144 TI - Amphetamine-type stimulant use and the risk of injury or death as a result of a road-traffic accident: A systematic review of observational studies. AB - Amphetamine-type substances are frequently detected among drivers injured or killed due to road-trauma. However, the role of this substance in crash causation remains equivocal. We performed a systematic review to evaluate existing evidence regarding the association between amphetamine use and the risk of injury or death due to road traffic accidents. A bibliographical search of PubMed, SafetyLit, Scopus, and Science Direct literature databases from 01 January 1980 until May 2015 was performed. The quality of included studies was assessed using the Newcastle-Ottowa Scale (NOS) (cut-off of >=7 indicated high quality). Inter-rater reliability between three independent reviewers for the NOS was calculated using Cohens kappa (kappa) statistic, and best-evidence synthesis was performed. A total of 182 articles were found. Nine studies met eligibility criteria for inclusion for review, and seven studies were included for best-evidence synthesis. Best-evidence synthesis demonstrated a conflicting level of evidence for associations between the use of-amphetamine-type substances and the risk of sustaining an injury, and a moderate level of evidence between amphetamine use and the risk of death due to road trauma. This is the first review to synthesise evidence regarding the association between amphetamine-type substance use and the risk of injury or death due to a road traffic accident. More conclusive evidence of death due to road trauma among amphetamine users may reflect significant and global deficits in functioning associated with effective vehicular control under the influence of this substance. Additional high quality, sufficiently powered studies are required to elucidate the magnitude of these associations. PMID- 27006145 TI - Advanced colorectal neoplasia: The importance of adequate classification. PMID- 27006146 TI - Comparison of Blood Loss After Total Hip Arthroplasty Between Ankylosing Spondylitis and Osteoarthritis. AB - BACKGROUND: This study was conducted to compare the blood loss during primary total hip arthroplasty (THA) between ankylosing spondylitis (AS) and hip osteoarthritis (OA). METHODS: We reviewed 120 THAs in 68 patients comprising 3 groups: AS with total bony ankylosis of the hips (ASB), AS with stiff hips (ASS), and OA. Demographics, perioperative laboratory values, intraoperative data, blood loss, transfusion rate, transfusion reactions, surgical complications, hospitalization cost, and length of stay (LOS) were collected and analyzed among ASB, ASS, and OA groups. RESULTS: The patients of the ASB and ASS groups were much younger and thinner than those of the OA group. There were no significant differences in the preoperative values of activated partial thromboplastin time, prothrombin time, and international normalized ratio among the 3 groups (all P > .05). The intraoperative blood loss, volume of drainage, hidden blood loss, transfusion rate, transfusion reactions, and hospitalization cost in the ASB group were significantly higher than in the other 2 groups, although not significantly different between the ASS and OA groups (P > .05). CONCLUSION: Both AS and OA can cause hyperosteogeny to the hips, but ASB patients have more serious symptoms in their affected hips. This may cause more blood loss in THA surgery because of bone surface bleeding. The reason that ASB patients suffered more blood loss may be related to the high difficulty and long duration of the operation. PMID- 27006147 TI - Midterm Survivorship of the Lefevre Constrained Liner: A Consecutive Multisurgeon Series of 166 Cases. AB - BACKGROUND: Constrained liners are used as part of a salvage procedure to provide stability for patients at high risk for dislocation after a total hip arthroplasty. However, no recent studies exist highlighting their effectiveness and/or limitations. METHOD: This prospective review included 166 consecutive hip arthroplasties, either primary (27%) or revision (73%), with a unique design of a constrained liner: Lefevre retentive cup. There were 113 females (69%), and the average age at index surgery was 75.9 years (range, 35-94). The mean follow-up was 6.2 years (range, 0.3-11). RESULTS: Twenty patients had a reoperation; 10 for infection (4 acute and 6 chronic joint infection) and 10 for cup failure (5 fixation failure, 3 aseptic loosening, and 2 dislocation). Ten-year survivals for cup revision were 89% (CI, 83-94) and 92% (CI, 89-97) for all revision and revision for noninfectious reasons, respectively. When solely evaluating for dislocation, the survival at 10 years was 99% (CI, 97-100). Considering primary and revision cases, 10-year survivals cup revision for aseptic reasons were 92.4% (CI, 84-100) and 92.5% (CI, 87-98), respectively. CONCLUSIONS: The Lefevre retentive cup demonstrated excellent 10-year's survivorship. With the rate of aseptic loosening around 2% and a dislocation rate around 1%, the cup is as effective as other available devices and is therefore a cost-effective tool to reduce the risk of dislocation in at-risk patients undergoing hip arthroplasty. PMID- 27006148 TI - Greater Wound and Renal Complications in Gout Patients Undergoing Total Joint Arthroplasty. AB - BACKGROUND: Little is known about total joint arthroplasty (TJA) outcomes in gout patients. The purpose of this study was to compare adverse events between gout and nongout patients who underwent primary TJA. METHODS: Using our institutional database and medical records review, a retrospective case-control study was conducted. From 2000 to 2012, a total of 482 gout TJA patients were matched with nongout TJA patients in a 1:1 ratio. Length of stay, complications, 90-day emergency room visits, and 90-day readmissions in these patients were compared. RESULTS: Gout patients had greater wound healing problems (12.2% vs 5.0%, P = .001) and renal complications (8.9% vs 3.1%, P = .0003) compared with nongout patients. There were no significant differences between gout and nongout patients in terms of mean length of hospital stay (3.82 vs 3.17 days, P = .11) and 90-day emergency room visits (5.6% vs 3.5%, P = 1.00). Subgroup analysis showed that 90 day readmission rates were higher in gout patients who underwent total hip arthroplasty compared with those in nongout THA patients (6.8% vs 2.1%, P = .02). CONCLUSION: Gout patients undergoing TJA have greater wound healing problems and renal complications. Surgeons should be cognizant of fluid management, renal monitoring and wound issues and should be cautious when treating TJA gout patients. PMID- 27006149 TI - Benefit-cost Trade-offs of Early Learning in Foraging Predatory Mites Amblyseius Swirskii. AB - Learning is changed behavior following experience, and ubiquitous in animals including plant-inhabiting predatory mites (Phytoseiidae). Learning has many benefits but also incurs costs, which are only poorly understood. Here, we addressed learning, especially its costs, in the generalist predatory mite Amblyseius swirskii, a biocontrol agent of several herbivores, which can also survive on pollen. The goals of our research were (1) to scrutinize if A. swirskii is able to learn during early life in foraging contexts and, if so, (2) to determine the costs of early learning. In the experiments, we used one difficult-to-grasp prey, i.e., thrips, and one easy-to-grasp prey, i.e., spider mites. Our experiments show that A. swirskii is able to learn during early life. Adult predators attacked prey experienced early in life (i.e., matching prey) more quickly than they attacked unknown (i.e., non-matching) prey. Furthermore, we observed both fitness benefits and operating (physiological) costs of early learning. Predators receiving the matching prey produced the most eggs, whereas predators receiving the non-matching prey produced the least. Thrips-experienced predators needed the longest for juvenile development. Our findings may be used to enhance A. swirskii's efficacy in biological control, by priming young predators on a specific prey early in life. PMID- 27006150 TI - The Effect of Age on the Pharmacokinetics of Udenafil in Healthy Subjects. AB - Udenafil, a cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor, has been developed to treat erectile dysfunction. We evaluated the effect of age on the pharmacokinetics and tolerability of udenafil. A single center, open-label, parallel-group phase 1 study was conducted in healthy adult subjects who took a single oral dose of udenafil (100 mg). The pharmacokinetics and tolerability of udenafil were compared between 12 healthy young men (21-27 years) and 12 healthy elderly men (65-78 years). Serial blood and urine samples were collected for up to 60 and 48 hours after dosing. The plasma concentrations of udenafil and its major metabolite, DA-8164, were analyzed using a validated liquid chromatography-tandem mass spectrometry method. The mean Cmax of udenafil tended to be slightly less (214.0 vs 292.8 MUg/L) in the elderly compared with the young (GMR, 68.9; 95% CI, 48.9-97.1); however, the AUC did not differ between the groups (1858.8 vs 2100.6 MUg.h/L; GMR, 84.6; 95% CI, 66.1-108.4). The mean t1/2 was prolonged by approximately 5 hours in the elderly (P < .05). The clearance and metabolic AUC ratio did not differ between the elderly and young. In terms of tolerability, all adverse events were mild, and all subjects recovered without additional therapy. The systemic exposure of elderly subjects to udenafil appears to be comparable to or slightly less than that of young healthy subjects. Based on our pharmacokinetic comparisons, udenafil dose adjustment is unlikely to be required in the elderly population. PMID- 27006151 TI - Combination of Gefitinib and Pemetrexed Prevents the Acquisition of TKI Resistance in NSCLC Cell Lines Carrying EGFR-Activating Mutation. AB - INTRODUCTION: Development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is a clinical issue in patients with epidermal growth factor receptor gene (EGFR)-mutated non-small cell lung cancer (NSCLC). The aim of this study was to investigate the potential of combining gefitinib and pemetrexed in preventing the acquisition of resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines harboring EGFR exon 19 deletion. METHODS: The effect of different combinatorial schedules of gefitinib and pemetrexed on cell proliferation, cell cycle, apoptosis, and acquisition of gefitinib resistance in PC9 and HCC827 NSCLC cell lines and in PC9 xenograft models was investigated. RESULTS: Simultaneous treatment with gefitinib and pemetrexed enhanced cell growth inhibition and cell death and prevented the appearance of gefitinib resistance mediated by T790M mutation or epithelial-to-mesenchymal transition (EMT) in PC9 and HCC827 cells, respectively. In PC9 cells and in PC9 xenografts the combination of gefitinib and pemetrexed, with different schedules, prevented gefitinib resistance only when pemetrexed was the first treatment, given alone or together with gefitinib. Conversely, when gefitinib alone was administered first and pemetrexed sequentially alternated, a negative interaction was observed and no prevention of gefitinib resistance was documented. The mechanisms of resistance that developed in vivo included T790M mutation and EMT. The induction of EMT was a feature of tumors treated with gefitinib when given before pemetrexed, whereas T790M was recorded only in tumors treated with gefitinib alone. CONCLUSIONS: The combination of gefitinib and pemetrexed is effective in preventing gefitinib resistance; the application of intermittent treatments requires that gefitinib not be administered before pemetrexed. PMID- 27006152 TI - Prevalence of Non-Left Anterior Descending Septal Perforator Culprit in Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation. AB - Identifying the coronary branch that supplies the basal septum is the cornerstone for successful alcohol septal ablation (ASA). The basal septum is often supplied by septal perforator artery/arteries (SPA/SPAs) not originating from the left anterior descending (LAD) coronary artery. We aim to investigate the prevalence and significance of non-LAD septal "culprit" in patients undergoing ASA. A retrospective review of patients who underwent ASA from 2006 to 2014 was conducted. Procedural and midterm outcomes of patients who had ASA of LAD and non LAD culprit SPA were reported. A total 89 patients were included in the analysis; 13 patients (15%) had ASA of non-LAD SPA. These patients were more likely to have a history of failed ASA, more than one SPA treated, more ethanol dose injected, longer procedures, and higher contrast use compared with those who had ASA of LAD SPA. In-hospital outcomes, residual gradient, symptom improvement, and midterm mortality were similar in the 2 groups. In conclusion, in a cohort of patients undergoing ASA, 15% had ablation of SPA culprit that did not originate from the LAD. Half of these patients had previous unsuccessful ASA. Systematic screening for the ideal culprit SPA with nonselective coronary injection of echo contrast should be used to avoid incomplete or failed ASA. PMID- 27006153 TI - Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. AB - Hypertrophic cardiomyopathy (HC) is the most common genetic heart disease and an important cause of sudden death and heart failure symptoms. The current prevalence for HC (1:500) is based on echocardiographic population studies in which a substantial proportion of affected subjects have not come to clinical recognition. Therefore, we sought to define the subset of patients with HC who are diagnosed in the US. A proprietary integrated claims database including medical condition International Classification of Diseases, Ninth Revision diagnostic codes for over 160 million individual patients in the US was interrogated for 2013 to identify the prevalence of clinically recognized HC. Patients with >=1 claim for any of the HC International Classification of Diseases, Ninth Revision diagnosis codes from January to December 2013 were identified. The combined occurrence rate of HC was stratified by age and gender and multiplied by the 2013 United States population in the same age/gender categories to produce the final projected prevalence. The analysis was performed on 169,089,614 patients, of whom 59,009 unique patients were identified with >=1 claim for HC. The projected estimated occurrence of diagnosed HC in the US in 2013 was 1:3,195 for a total of 98,958 subjects. Average age at HC diagnosis was in the fifth decade of life, with 43% of the cohort composed of women. In conclusion, leveraging a claims-based data analytic technique, about 100,000 patients are diagnosed clinically with HC in the US, an occurrence which is less than the prevalence reported in systematic population studies based on echocardiographic diagnosis. This observation supports the view that many patients with HC are undiagnosed throughout life and enhances our understanding of the burden of this genetic heart disease on the health care system. PMID- 27006154 TI - Multidirectional manual arm strength and its relationship with resultant shoulder moment and arm posture. AB - Previous work has quantified manual force capabilities for ergonomics design, but the number of studies and range of conditions tested are limited in scope. Therefore, the aims of this study were to collect seated manual arm strength (MAS) data from 24 females in several unique exertion directions (n = 26) and hand locations relative to the shoulder (n = 8), and to investigate the associations between MAS and shoulder/elbow moments. MAS was generally highest when the direction of force application was oriented parallel to the vector from the shoulder to knuckle, and weakest when oriented orthogonal to that vector. Moderate correlations were found between MAS and: (1) resultant shoulder moment (r = 0.34), (2) resultant moment arms (r = -0.545) and (3) elbow flexion/extension moment (r = 0.481). Our strength data will be used in the development of a comprehensive MAS predictive method, so that strength capabilities can be predicted to help design acceptable tasks in the workplace. Practitioner Summary: This study sought to enhance our understanding of one handed manual arm strength capabilities for ergonomics task evaluations. Our findings provide researchers and practitioners with manual strength data for off axis force directions, as well as hand locations not previously measured. These data will contribute to future methods for predicting strength capabilities. PMID- 27006155 TI - Vesicles as Vehicles for Virulence. AB - Parasites have long been known to influence host responses to infection through the secretion of virulence factors. Extracellular vesicles are emerging as important mediators of these manipulations, and a new study by Szempruch et al. suggests they could play a crucial role in host responses to African trypanosome infections. PMID- 27006156 TI - A Multidisciplinary Pulmonary Embolism Response Team: Initial 30-Month Experience With a Novel Approach to Delivery of Care to Patients With Submassive and Massive Pulmonary Embolism. AB - BACKGROUND: Integrating newly developed tests and treatments for severe pulmonary embolism (PE) into clinical care requires coordinated multispecialty collaboration. To meet this need, we developed a new paradigm: a multidisciplinary Pulmonary Embolism Response Team (PERT). In this report, we provide the first longitudinal analysis of patients treated by a PERT. METHODS: Our PERT includes specialists in cardiovascular medicine and surgery, emergency medicine, hematology, pulmonary/critical care, and radiology, and is organized as a rapid response team. We prospectively captured clinical, therapeutic, and outcome data at PERT activation and during follow-up periods up to 365 days. We analyzed data collectively, and as five mutually exclusive 6-month periods. We performed Fisher exact tests and regression analysis to test for trend. RESULTS: In 30 months, there were 394 unique PERT activations, 314 (80%) for confirmed PE. PERT activations increased by 16% every 6 months. Most confirmed PEs were submassive (n = 143, 46%) or massive (n = 80, 26%). The PERT treated a relatively large proportion of patients with PE and systemic or catheter-directed thrombolysis (n = 35, 11%), though the most common treatment was anticoagulation alone (n = 215, 69%). Hemorrhagic complications were rare overall, especially among patients treated with catheter-directed thrombolysis. The all-cause 30-day mortality of PERT patients with confirmed PE was 12%. CONCLUSIONS: We report our initial 30-month experience with a novel multidisciplinary PERT that rapidly engages multiple specialists to deliver efficient, organized, and evidence-based care to patients with high-risk PE. The PERT paradigm was rapidly adopted and may become a new standard of care for patients with PE. PMID- 27006157 TI - Advances in Bronchial Thermoplasty. AB - Bronchial thermoplasty (BT) is a therapeutic intervention that delivers targeted thermal energy to the airway walls with the goal of ablating the smooth muscle in patients with severe persistent asthma. Since the publication of the original preclinical studies, three large randomized clinical trials evaluating its impact on asthma control have been performed. These trials have shown improvements in asthma-related quality of life and a reduction in asthma exacerbations following treatment with BT. However, there remains significant controversy regarding the true efficacy of BT and the interpretation of these studies, particularly the Asthma Intervention Research 2 trial. In this article, we will discuss these controversies and present the latest evidence on the use of BT in asthma, specifically the 5-year longitudinal evaluation of patients. In addition, we will discuss new insights into the histopathologic changes that occur in the airways following BT, as well as the feasibility of performing the procedure in patients with very severe asthma. We also will discuss the ongoing translational and clinical investigations regarding the underlying mechanism of action and methods to improve patient selection for this procedure. PMID- 27006163 TI - Calories or protein? The effect of dietary restriction on lifespan in rodents is explained by calories alone. AB - Almost exactly 100years ago Osborne and colleagues demonstrated that restricting the food intake of a small number of female rats extended their lifespan. In the 1930s experiments on the impact of diet on lifespan were extended by Slonaker, and subsequently McCay. Slonaker concluded that there was a strong impact of protein intake on lifespan, while McCay concluded that calories are the main factor causing differences in lifespan when animals are restricted (Calorie restriction or CR). Hence from the very beginning the question of whether food restriction acts on lifespan via reduced calorie intake or reduced protein intake was disputed. Subsequent work supported the idea that calories were the dominant factor. More recently, however, this role has again been questioned, particularly in studies of insects. Here we review the data regarding previous studies of protein and calorie restriction in rodents. We show that increasing CR (with simultaneous protein restriction: PR) increases lifespan, and that CR with no PR generates an identical effect. None of the residual variation in the impact of CR (with PR) on lifespan could be traced to variation in macronutrient content of the diet. Other studies show that low protein content in the diet does increase median lifespan, but the effect is smaller than the CR effect. We conclude that CR is a valid phenomenon in rodents that cannot be explained by changes in protein intake, but that there is a separate phenomenon linking protein intake to lifespan, which acts over a different range of protein intakes than is typical in CR studies. This suggests there may be a fundamental difference in the responses of insects and rodents to CR. This may be traced to differences in the physiology of these groups, or reflect a major methodological difference between 'restriction' studies performed on rodents and insects. We suggest that studies where the diet is supplied ad libitum, but diluted with inert components, should perhaps be called dietary or caloric dilution, rather than dietary or caloric restriction, to distinguish these potentially important methodological differences. PMID- 27006164 TI - The chemosensory receptors of codling moth Cydia pomonella-expression in larvae and adults. AB - Olfaction and gustation play critical roles in the life history of insects, mediating vital behaviors such as food, mate and host seeking. Chemosensory receptor proteins, including odorant receptors (ORs), gustatory receptors (GRs) and ionotropic receptors (IRs) function to interface the insect with its chemical environment. Codling moth, Cydia pomonella, is a worldwide pest of apple, pear and walnut, and behavior-modifying semiochemicals are used for environmentally safe control. We produced an Illumina-based transcriptome from antennae of males and females as well as neonate head tissue, affording a qualitative and quantitative analysis of the codling moth chemosensory receptor repertoire. We identified 58 ORs, 20 GRs and 21 IRs, and provide a revised nomenclature that is consistent with homologous sequences in related species. Importantly, we have identified several OR transcripts displaying sex-biased expression in adults, as well as larval-enriched transcripts. Our analyses have expanded annotations of the chemosensory receptor gene families, and provide first-time transcript abundance estimates for codling moth. The results presented here provide a strong foundation for future work on codling moth behavioral physiology and ecology at the molecular level, and may lead to the development of more precise biorational control strategies. PMID- 27006165 TI - Preparation of surface imprinted material of single enantiomer of mandelic acid with a new surface imprinting technique and study on its chiral recognition and resolution properties. AB - A surface imprinted material of the single enantiomer of mandelic acid with high performance was successfully prepared with a new surface imprinting technique of synchronously graft-polymerizing and molecule imprinting, and its enantiomeric recognition and resolution properties were investigated. Micro-sized silica gel particles were first modified with coupling agent gamma-mercaptopropyl trimethoxysilane (MPMS), obtaining the modified particles MPMS-SiO2 on which mercapto groups were introduced. A surface initiating system of -SH/BPO was constituted with the mercapto group (-SH) on MPMS-SiO2 particles and dibenzoyl peroxide (BPO) in N,N-dimethyl formamide (DMF) solution. In DMF solution, (R) mandelic acid molecule was used as the template and the functional monomer hydroxyethyl methylacrylate (HEMA) were combined together by right of multi-site hydrogen bonds. The free radicals produced on MPMS-SiO2 particles initiate HEMA molecules around (R)-mandelic acid molecules and the crosslinking agent N,N' Methylenebisacrylamide (MBA) to produce graft/crosslinking-polymerization. At the same time, the template (R)-mandelic acid molecules were enveloped within the thin grafted polymer layer on the surfaces of SiO2 particles, obtaining (R) mandelic acid surface imprinted material MIP-PHEMA/SiO2. The experimental results show that MIP-PHEMA/SiO2 particles have excellent enantiomeric recognition and resolution ability. The binding capacity of MIP-PHEMA/SiO2 particles for (R) mandelic acid reaches up to 278 mg/g. As the resolution experiment of a racemic mixture was carried out with MIP-PHEMA/SiO2 particles as solid adsorbent, relative another enantiomer, (S)-mandelic acid, the selectivity coefficient of the imprinted particles for (R)-mandelic acid is 5.02. As a consequence, the two enantiomers were well separated, and the optical purities (ee values) of the supernatant and eluant get up to 44% (corresponding to (S)-mandelic acid excess) and 85% (corresponding to (R)-mandelic acid excess), respectively. PMID- 27006166 TI - Water electrolysis on La(1-x)Sr(x)CoO(3-delta) perovskite electrocatalysts. AB - Perovskite oxides are attractive candidates as catalysts for the electrolysis of water in alkaline energy storage and conversion systems. However, the rational design of active catalysts has been hampered by the lack of understanding of the mechanism of water electrolysis on perovskite surfaces. Key parameters that have been overlooked include the role of oxygen vacancies, B-O bond covalency, and redox activity of lattice oxygen species. Here we present a series of cobaltite perovskites where the covalency of the Co-O bond and the concentration of oxygen vacancies are controlled through Sr(2+) substitution into La(1-x)Sr(x)CoO(3 delta) . We attempt to rationalize the high activities of La(1-x)Sr(x)CoO(3 delta) through the electronic structure and participation of lattice oxygen in the mechanism of water electrolysis as revealed through ab initio modelling. Using this approach, we report a material, SrCoO2.7, with a high, room temperature-specific activity and mass activity towards alkaline water electrolysis. PMID- 27006167 TI - Prediagnostic Helicobacter pylori Antibodies and Colorectal Cancer Risk in an Elderly, Caucasian Population. AB - BACKGROUND: Study results on overall seroprevalence of Helicobacter pylori and colorectal cancer risk have been inconsistent. However, one study found positive associations with antibodies to specific H. pylori proteins. To follow up on those findings, we assessed associations of 15 H. pylori specific proteins with colorectal cancer incidence in the prospective Cancer Prevention Study-II Nutrition Cohort. MATERIALS AND METHODS: Participants in this nested case-control study included 392 cases and 774 controls who were predominantly elderly (median age at blood draw: 71 years) and Caucasian (98%). Seroreactivity against 15 H. pylori proteins was assessed by fluorescent bead-based multiplex serology and associations with colorectal cancer were estimated using conditional logistic regression. RESULTS: Helicobacter pylori serostatus was not associated with colorectal cancer incidence (odds ratio (OR), 1.17, 95% confidence interval (95% CI), 0.91-1.50). Among individual antigens, GroEl serostatus was associated with colorectal cancer risk (OR, 1.32, 95% CI: 1.03-1.70), whereas CagM was associated with colon cancer risk only (OR, 1.35, 95% CI: 1.01-1.80). No dose-response relationships were observed for any of the antigens, including GroEl and CagM. CONCLUSIONS: The results of our study do not support an association between H. pylori infection and colorectal cancer risk in this elderly, mostly Caucasian population. PMID- 27006169 TI - Association of serum fatty acid and estimated desaturase activity with hypertension in middle-aged and elderly Chinese population. AB - We aimed to investigate the cross-sectional associations of serum fatty acid (FA) and related Delta-desaturase with hypertension among 2,447 community-dwellers aged 35-79 years living in Zhejiang Province, China. Individual FA was determined in serum, Delta(5)-desaturase (D5D) and Delta(6)-desaturase (D6D) activities were indirectly estimated by FA product/precursor ratios. Participants in the highest quartile of D5D component scores (20:4n-6, 20:5n-3, 22:6n-3 and D5D) have significantly lower odds of hypertension compared with individuals in the lowest (multivariate-adjusted odds ratio (OR) = 0.68, 95% CI: 0.46-0.98). When further stratified by gender, high D5D component scores were significantly associated with lower odds of hypertension in women (OR = 0.53, 95% CI: 0.35-0.80), but not in men (OR = 0.78, 95% CI: 0.52-1.18). Multivariate-adjusted prevalent OR for an interquartile increment of individual FA and estimated desaturase was 1.27 (95% CI: 1.08-1.50) for 16:0, 1.15 (95% CI: 1.01-1.30) for 16:1n-7, 0.89 (95% CI: 0.80 0.99) for 22:6n-3, 1.32 (95% CI: 1.01-1.72) for D6D (18:3n-6/18:2n-6), and 0.74 (95% CI: 0.56, 0.98) for D5D (20:4n-6/20:3n-6). Present findings suggested that high serum 22:6n-3 and D5D as well as low 16:0, 16:1n-7 and D6D were associated with a low prevalence of hypertension in this Chinese population. PMID- 27006168 TI - Purinergic signalling underlies transforming growth factor-beta-mediated bladder afferent nerve hyperexcitability. AB - KEY POINTS: The sensory components of the urinary bladder are responsible for the transduction of bladder filling and are often impaired with neurological injury or disease. Elevated extracellular ATP contributes, in part, to bladder afferent nerve hyperexcitability during urinary bladder inflammation or irritation. Transforming growth factor-beta1 (TGF-beta1) may stimulate ATP release from the urothelium through vesicular exocytosis mechanisms with minimal contribution from pannexin-1 channels to increase bladder afferent nerve discharge. Bladder afferent nerve hyperexcitability and urothelial ATP release with CYP-induced cystitis is decreased with TGF-beta inhibition. These results establish a causal link between an inflammatory mediator, TGF-beta, and intrinsic signalling mechanisms of the urothelium that may contribute to the altered sensory processing of bladder filling. ABSTRACT: The afferent limb of the micturition reflex is often compromised following bladder injury, disease and inflammatory conditions. We have previously demonstrated that transforming growth factor-beta (TGF-beta) signalling contributes to increased voiding frequency and decreased bladder capacity with cystitis. Despite the functional presence of TGF-beta in bladder inflammation, the precise mechanisms of TGF-beta mediating bladder dysfunction are not yet known. Thus, the present studies investigated the sensory components of the urinary bladder that may underlie the pathophysiology of aberrant TGF-beta activation. We utilized bladder-pelvic nerve preparations to characterize bladder afferent nerve discharge and the mechanisms of urothelial ATP release with distention. Our findings indicate that bladder afferent nerve discharge is sensitive to elevated extracellular ATP during pathological conditions of urinary bladder inflammation or irritation. We determined that TGF beta1 may increase bladder afferent nerve excitability by stimulating ATP release from the urothelium via vesicular exocytosis mechanisms with minimal contribution from pannexin-1 channels. Furthermore, blocking aberrant TGF-beta signalling in cyclophosphamide-induced cystitis with TbetaR-1 inhibition decreased afferent nerve hyperexcitability with a concomitant decrease in urothelial ATP release. Taken together, these results establish a role for purinergic signalling mechanisms in TGF-beta-mediated bladder afferent nerve activation that may ultimately facilitate increased voiding frequency. The synergy between intrinsic urinary bladder signalling mechanisms and an inflammatory mediator provides novel insight into bladder dysfunction and supports new avenues for therapeutic intervention. PMID- 27006170 TI - Association between obesity and suicide in woman, but not in man: a population based study of young adults. AB - The relationship between obesity and suicide risk is still unclear with controversial research results. The aim of this study is to investigate the relationship between obesity and suicide risk for men and women in a population based study of young adults. This is a cross-sectional population-based study that identified young adults between 18 and 35 years of age. Suicide risk was investigated through the structured clinical interview Mini. Weight and height were assessed, and participants were classified as normal-weight body mass index (BMI < 30) or obese (BMI > 30). The prevalence of obesity was of 19.9% of the total sample (n = 1953). Obesity was more prevalent among women and participants between 27 and 35 years of age. Suicide risk was present in 13.0% of the sample and more prevalent among women. In our study we found an association between obesity and suicide risk for women, but not for men. Obesity was associated with a higher prevalence of suicide risk in women. Given the strength of the relationship between BMI and suicide, identifying the mechanisms associated with obesity, especially for women, can lead to new insights into the prevention of suicide risk. PMID- 27006171 TI - Estimating the impact from Fukushima in Southern Spain by 131I and Accelerator Mass Spectrometry detection of 129I. AB - After the Fukushima accident, large amounts of radionuclides were discharged to the atmosphere. Some of them travelled long distances and were detected in places as far from Japan as Spain a few days after the accident. One of these radionuclides was 131I. Its isotope 129I (T1/2 = 15.7 * 106 years) was also expected to follow the same pathway. In this work, we present the results for the 129I concentration in the same atmospheric samples from Seville (Spain) where 131I activity was measured in 2011 by Baeza et al. (2012). 129I concentrations in aerosol and gaseous samples showed concentrations in the order of 104 and 105 atoms/m3, typically higher in the gaseous form with respect to the aerosol form. Also 129I in rainwater was measured, showing concentrations in the order of 108 atoms/L. The results show a very good agreement with the 131I profile, showing that, if background from other sources is not relevant, it is possible to estimate the impact of similar events years after them thanks to the sensitivity of techniques like Accelerator Mass Spectrometry. PMID- 27006172 TI - The mating system of the true fruit fly Bactrocera tryoni and its sister species, Bactrocera neohumeralis. AB - The frugivorous "true" fruit fly, Bactrocera tryoni (Queensland fruit fly), is presumed to have a nonresourced-based lek mating system. This is largely untested, and contrary data exists to suggest Bactrocera tryoni may have a resource-based mating system focused on fruiting host plants. We tested the mating system of Bactrocera tryoni, and its close sibling Bactrocera neohumeralis, in large field cages using laboratory reared flies. We used observational experiments that allowed us to determine if: (i) mating pairs were aggregated or nonaggregated; (ii) mating system was resource or nonresource based; (iii) flies utilized possible landmarks (tall trees over short) as mate rendezvous sites; and (iv) males called females from male-dominated leks. We recorded nearly 250 Bactrocera tryoni mating pairs across all experiments, revealing that: (i) mating pairs were aggregated; (ii) mating nearly always occurred in tall trees over short; (iii) mating was nonresource based; and (iv) that males and females arrived at the mate-rendezvous site together with no evidence that males preceded females. Bactrocera neohumeralis copulations were much more infrequent (only 30 mating pairs in total), but for those pairs there was a similar preference for tall trees and no evidence of a resource-based mating system. Some aspects of Bactrocera tryoni mating behavior align with theoretical expectations of a lekking system, but others do not. Until evidence for unequivocal female choice can be provided (as predicted under a true lek), the mating system of Bactrocera tryoni is best described as a nonresource based, aggregation system for which we also have evidence that land-marking may be involved. PMID- 27006173 TI - Iraq and Afghanistan Veterans report symptoms consistent with chronic multisymptom illness one year after deployment. AB - Many Veterans returning from service in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) experience chronic pain. What is not known is whether for some OIF/OEF Veterans this pain is part of a larger condition of diffuse multisystem symptoms consistent with chronic multisymptom illness (CMI). We use data from a prospective longitudinal study of OIF/OEF Veterans to determine the frequency of CMI. We found that 1 yr after deployment, 49.5% of OIF/OEF Veterans met criteria for mild to moderate CMI and 10.8% met criteria for severe CMI. Over 90% of Veterans with chronic pain met criteria for CMI. CMI was not completely accounted for either by posttraumatic stress disorder or by predeployment levels of physical symptoms. Veterans with symptoms consistent with CMI reported significantly worse physical health function than Veterans who did not report symptoms consistent with CMI. This study suggests that the presence of CMI should be considered in the evaluation of OIF/OEF Veterans. Further, it suggests the pain management for these Veterans may need to be tailored to take CMI into consideration. PMID- 27006174 TI - The promise of molecular profiling of choroid plexus tumors for diagnostic and prognostic stratification: where to go from here? PMID- 27006175 TI - Elevated levels of polymorphonuclear myeloid-derived suppressor cells in patients with glioblastoma highly express S100A8/9 and arginase and suppress T cell function. AB - BACKGROUND: Gliomas are primary brain tumors that are associated with a poor prognosis. The introduction of new treatment modalities (including immunotherapy) for these neoplasms in the last 3 decades has resulted in only limited improvement in survival. Gliomas are known to create an immunosuppressive microenvironment that hampers the efficacy of (immuno)therapy. One component of this immunosuppressive environment is the myeloid-derived suppressor cell (MDSC). METHODS: We set out to analyze the presence and activation state of MDSCs in blood (n = 41) and tumor (n = 20) of glioma patients by measuring S100A8/9 and arginase using flow cytometry and qPCR. Inhibition of T cell proliferation and cytokine production after stimulation with anti-CD3/anti-CD28 coated beads was used to measure in vitro MDSC suppression capacity. RESULTS: We report a trend toward a tumor grade-dependent increase of both monocytic (M-) and polymorphonuclear (PMN-) MDSC subpopulations in the blood of patients with glioma. M-MDSCs of glioma patients have increased levels of intracellular S100A8/9 compared with M-MDSCs in healthy controls (HCs). Glioma patients also have increased S100A8/9 serum levels, which correlates with increased arginase activity in serum. PMN-MDSCs in both blood and tumor tissue demonstrated high expression of arginase. Furthermore, we assessed blood-derived PMN-MDSC function and showed that these cells have potent T cell suppressive function in vitro. CONCLUSIONS: These data indicate a tumor grade-dependent increase of MDSCs in the blood of patients with a glioma. These MDSCs exhibit an increased activation state compared with MDSCs in HCs, independent of tumor grade. PMID- 27006176 TI - Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: a report of the Children's Oncology Group ACNS0423 study. AB - BACKGROUND: The prognosis for children with malignant glioma is poor. This study was designed to determine whether lomustine and temozolomide following radiotherapy and concurrent temozolomide improves event-free survival (EFS) compared with historical controls with anaplastic astrocytoma (AA) or glioblastoma (GBM) and whether survival is influenced by the expression of O6 methylguanine-DNA-methyltransferase (MGMT). METHODS: Following maximal surgical resection, newly diagnosed children with nonmetastatic high-grade glioma underwent involved field radiotherapy with concurrent temozolomide. Adjuvant chemotherapy consisted of up to 6 cycles of lomustine 90 mg/m(2) on day 1 and temozolomide 160 mg/m(2)/day *5 every 6 weeks. RESULTS: Among the 108 eligible patients with AA or GBM, 1-year EFS was 0.49 (95% CI, 0.39-0.58), similar to the original CCG-945-based design model. However, EFS and OS were significantly improved in ACNS0423 compared with the 86 AA or GBM participants treated with adjuvant temozolomide alone in the recent ACNS0126 study (1-sided log-rank P = .019 and .019, respectively). For example, 3-year EFS was 0.22 (95% CI, 0.14 0.30) in ACNS0423 compared with 0.11 (95% CI, 0.05-0.18) in ACNS0126. Stratifying the comparison by resection extent, the addition of lomustine resulted in significantly better EFS and OS in participants without gross-total resection (P = .019 and .00085 respectively). The difference in EFS and OS was most pronounced for participants with GBM (P = .059 and 0.051, respectively), and those with MGMT overexpression (P = .00036 and .00038, respectively). CONCLUSION: The addition of lomustine to temozolomide as adjuvant therapy in ACNS0423 was associated with significantly improved outcome compared with the preceding COG ACNS0126 HGG study in which participants received temozolomide alone. PMID- 27006177 TI - MiR-301a is activated by the Wnt/beta-catenin pathway and promotes glioma cell invasion by suppressing SEPT7. AB - BACKGROUND: miR-301a is frequently dysregulated and specific to human tumors, playing a critical role in tumorigenesis; however, the exact functions and regulatory mechanisms of miR-301a in glioma cells remain largely unknown. Herein, we show that miR-301a activated by the Wnt/beta-catenin pathway promoted the invasion of glioma cells by directly targeting SEPT7. METHODS: Biochemical, luciferase reporter, and hromatin immunoprecipitation PCR assays characterized the function and regulatory mechanisms of miR-301a in glioma invasion. RESULTS: Initially, we detected the expression of miR-301a in glioma tissues and identified that miR-301a had increased, with ascending grades of the tumor. Furthermore, high levels of miR-301a were associated with a poorer prognosis in glioma patients. It is important to note that the Wnt/beta-catenin/TCF4 pathway enhanced miR-301a expression by binding to the promoter region. To determine the oncogenic functions of miR-301a in glioma, SEPT7 was supported as the direct target gene. In addition, the Wnt/beta-catenin pathway repressed SEPT7 expression, which was dependent on miR-301a in glioma cells. Finally, miR-301a was activated by Wnt/beta-catenin and then promoted invasion of glioma cells by inhibiting the expression of SEPT7 in vitro and in vivo. CONCLUSIONS: Our findings revealed the mechanism of action for miR-301a in tumor cell invasion. Moreover, the Wnt/miR-301a/SEPT7 signaling axis might be a novel target in treating glioma. PMID- 27006178 TI - Upfront bevacizumab may extend survival for glioblastoma patients who do not receive second-line therapy: an exploratory analysis of AVAglio. AB - BACKGROUND: In this post-hoc, exploratory analysis, we examined outcomes for patients enrolled in the AVAglio trial of front-line bevacizumab or placebo plus radiotherapy/temozolomide who received only a single line of therapy. METHODS: Patients with newly diagnosed glioblastoma received protocol-defined treatment until progressive disease (PD). Co-primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). After confirmed PD, patients were treated at the investigators' discretion. PFS/OS were assessed in patients with a PFS event who did not receive post-PD therapy (Group 1) and patients with a PFS event who received post-PD therapy plus patients who did not have a PFS event at the final data cutoff (Group 2). Kaplan-Meier methodology was used. A multivariate Cox proportional hazards model for known prognostic variables was generated. RESULTS: Baseline characteristics were balanced. In patients with a PFS event who did not receive post-PD therapy (Group 1; n = 225 [24.4% of the intent-to-treat population]), the addition of bevacizumab to radiotherapy/temozolomide resulted in a 3.6-month extension in both median PFS (hazard ratio [HR]: 0.62, P = .0016) and median OS (HR: 0.67, P = .0102). Multivariate analyses supported this OS benefit (HR: 0.66). In the remaining patients (Group 2; n = 696), a 5.2-month PFS extension was observed in bevacizumab-treated patients (HR: 0.61, P < .0001); OS was comparable between the treatment arms (HR: 0.88, P = .1502). No significant differences in safety were observed between the 2 groups. CONCLUSION: This exploratory analysis suggests that the addition of bevacizumab to standard glioblastoma treatment prolongs PFS and OS for patients with PD who receive only one line of therapy. PMID- 27006179 TI - Pharmacokinetic comparison of five tanshinones in normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan or its single herb extract by UPLC MS/MS. AB - A fast, sensitive and reliable ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for simultaneous quantitation and pharmacokinetic study of five tanshinones (tanshinone I, tanshinone IIA, tanshinone IIB, dihydrotanshinone I, cryptotanshinone), the bio-active ingredients of Huo Luo Xiao Ling Dan (HLXLD) in rat plasma. After liquid-liquid extraction, chromatographic separation was accomplished on a Shim-pack XR-ODS column (75 * 3.0 mm, 2.2 um particles) and eluted with a mobile phase consisting of acetonitrile-0.05% formic acid aqueous solution (80:20, v/v) at a flow rate of 0.4 mL/min, and the total run time was 7.0 min. The detection was performed on a triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source in positive ionization and multiple reaction monitoring mode. The lower limits of quantification were 0.050-0.400 ng/mL for all the analytes. Linearity, precision and accuracy, the mean extraction recoveries and matrix effects all satisfied criteria for acceptance. This validated method was successfully applied to a comparative pharmacokinetic study of five bio-active components in rat plasma after oral administration of HLXLD or Salvia miltiorrhiza extract in normal and arthritic rats. The results showed that there were different pharmacokinetic characteristics among different groups. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27006180 TI - Quality of oxytocin available in low- and middle-income countries: a systematic review of the literature. AB - BACKGROUND: Oxytocin is the drug of choice for preventing and treating postpartum haemorrhage, an important cause of maternal death. Oxytocin is widely available in low and middle-income countries (LMIC) but there are concerns about its quality. OBJECTIVE: To identify, critically appraise and synthesise the findings of studies on the quality of oxytocin available in LMIC. SEARCH STRATEGY: We searched seven electronic databases, without language restriction. SELECTION CRITERIA: Studies reporting results of tests to assess quality of oxytocin samples from LMIC. DATA COLLECTION AND ANALYSIS: Study selection, data extraction and quality assessment were performed in duplicate. Results are presented descriptively. MAIN RESULTS: The search identified 2611 unique citations; eight studies, assessing 559 samples from 15 different countries were included. Most samples were collected from facility level settings (n = 509) and from the private sector (n = 321). The median prevalence of oxytocin samples that failed quality tests was 45.6% (range 0-80%), mostly due to insufficient amounts of active pharmacological ingredient. Over one-third of the samples (n = 204) had low (<90%) oxytocin content indicating substandard medicine; two samples had no active ingredient, suggesting possible counterfeit drugs. The proportion of low fails was higher in samples collected in Africa than in Asia or Latin America (57.5% versus 22.3% versus 0%, respectively, P < 0.0001), in private than in public sectors (34.0% versus 25.3%, P = 0.032) and in facilities than in central distributors (37.9% versus 22.0%, P = 0.030). CONCLUSION: There is a high prevalence of poor-quality oxytocin samples in LMIC countries, mainly due to inadequate amounts of active ingredient. TWEETABLE ABSTRACT: Systematic review points to problems with quality of oxytocin samples from low- and middle-income countries. PMID- 27006181 TI - Harmonic technology versus neodymium-doped yttrium aluminium garnet laser and electrocautery for lung metastasectomy: an experimental study. AB - OBJECTIVES: We compared the efficacy of non-anatomical lung resections with that of three other techniques: monopolar electrocautery; neodymium-doped yttrium aluminium garnet laser and harmonic technology. We hypothesized that the thermal damage with harmonic technology could be reduced because of the lower temperatures generated by harmonic technology compared with that of other devices. METHODS: Initial studies were performed in 13 isolated pig lungs for each group. A 1.5-cm capsule was inserted within the lung to mimic a tumour and a total of 25 non-anatomical resections were performed with each device. The damage of the resected lung surface and of the tumour border were evaluated according to the colour (ranging from 0-pink colour to 4-black colour), histological (ranging from Score 0-no changes to Score 3-presence of necrotic tissue) and radiological (ranging from Score 0-isointense T2 signal at magnetic resonance imaging to Score 3-hyperintense T2 signal) criteria. A total of seven non-anatomical resections with harmonic technology were also performed in two live pigs to assess if ex vivo results could be reproducible in live pigs with particular attention to haemostatic and air-tightness properties. RESULTS: In the ex vivo lung, there was a statistical significant difference between depth of thermal damage (P < 0.0001) in electrocautery (1.3 [1.2-1.4]), laser (0.9 [0.6-0.9]) and harmonic (0.4 [0.3 0.5]) groups. Electrocautery had a higher depth of thermal damage compared with that of the laser (P = 0.01) and harmonic groups (P = 0.0005). The harmonic group had a less depth of thermal damage than that of the laser group (P = 0.01). Also, histological damages of tumour borders (P < 0.001) and resected lung surface (P < 0.001), radiological damage of tumour borders (P < 0.001) and resected lung surface (P < 0.001) and colour changes (P < 0.001) were statistically different between three study groups. Resections of in vivo pig lungs showed no bleeding; 2 of 7 cases of low air leaks were found; however, they ceased by sealing lung parenchyma with harmonic technology. CONCLUSIONS: Our experimental data support the resections performed with the use of harmonic technology. The lack of severe tissue alterations could favour healing of parenchyma, assure air tightness and preserve functional lung parenchyma. However, randomized controlled studies are needed in an in vivo model to corroborate our findings. PMID- 27006182 TI - A new endoscopic hand drill for management of tracheal stenosis. AB - Tracheal resection and primary anastomosis is the treatment of choice for the management of benign tracheal stenoses. Rigid endoscopy with laser-assisted mechanical dilatation is an alternative to surgery and helps to improve symptoms and quality of life in patients unfit for surgery. Here, we describe the treatment of a simple web-like stenosis, using a new endoscopic hand drill that was assembled by sharpening the blunt tip of a standard endoscopic cotton applicator. The bronchoscopy was positioned proximally to the stenotic lesion and radial holes were made at 12, 3 and 9 o'clock. The tip of instrument touched the target area of the stenotic scar. The proximal end was handily rotated and the force, applied on the instrument's tip, and the hole was drilled. Next, endoscopic scissors was placed in the drill holes and the stenotic scar was cut. Mechanical dilatation with rigid bronchoscopes of increasing diameters completed the procedure. This procedure was successfully applied in 5 patients with simple benign tracheal stenosis and unfit for surgery. No intraoperative and/or postoperative complications occurred. No recurrence of stenosis was detected after a mean follow-up of 26 +/- 2 months. PMID- 27006183 TI - Circulating cytokine portraits can differentiate between allograft rejection and pulmonary infection in cardiac transplant rats. AB - OBJECTIVES: Cardiac rejection and infection are the leading causes of morbidity and mortality after transplant representing with similar non-specific symptoms. Early discrimination is crucial yet challenging. We proposed that aberrant serum cytokine portraits exist in pulmonary infection and allograft rejection, and such profiles might aid in timely differential diagnosis. METHODS: Lewis rat received Wistar rat heart allografts. Allograft rejection (n = 5) and pulmonary infection (n = 7) were induced via cessation of cyclosporine injection and intratracheal inoculation of Pseudomonas aeruginosa, respectively, and pathologically confirmed. A non-rejection and non-infection group (n = 5) was served as healthy controls. The circulating cytokine profiles of the study objects were then simultaneously measured using a multiplex quantitative cytokine array. RESULTS: Thirteen cytokines [B7-2, beta-nerve growth factor (NGF), chemokine (C-X3-C motif) ligand 1 (Fractalkine), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin beta (IL-beta), IL-2, IL-4, IL-10, chemokine (C-X-C motif) ligand 5 (LIX), L-selectin, chemokine (C-C motif) ligand 2 (MCP-1), brain creatine kinase (TCK-1) and tumour necrosis factor alpha (TNF-alpha)] were up-regulated in allograft rejecting animals. Among them, B7-2, beta-NGF, Fractalkine, GM-CSF, IFN-gamma, IL-beta, IL-2, IL-4, LIX, MCP-1 and TCK 1 were significantly increased compared with infection rats (all P-values <0.05). B7-2, CNIC-1 and CNIC-2 were increased in infection animals when compared with healthy controls (900.85 +/- 259.30 vs 175.04 +/- 161.07 pg/ml, 319.68 +/- 264.91 vs 13.50 +/- 0.00 pg/ml and 51.424 +/- 29.51 vs 5.24 +/- 1.30 pg/ml, respectively, all P-values <0.05). CONCLUSIONS: The present study demonstrated fluctuations in circulating cytokine portraits in cardiac allograft rejection and bacterial pulmonary infection after transplant. Such disease-specific cytokine patterns might facilitate early discrimination between rejection and infection. PMID- 27006184 TI - Immunochemical faecal occult blood testing to screen for colorectal cancer: can the screening interval be extended? AB - OBJECTIVE: Colorectal cancer (CRC) screening programmes based on faecal immunochemical testing for haemoglobin (FIT) typically use a screening interval of 2 years. We aimed to estimate how alternative FIT strategies that use a lower than usual positivity threshold followed by a longer screening interval compare with conventional strategies. METHODS: We analysed longitudinal data of 4523 Dutch individuals (50-74 years at baseline) participating in round I of a one sample FIT screening programme, of which 3427 individuals also participated in round II after 1-3 years. The cohort was followed until 2 years after round II. In both rounds, a cut-off level of >=50 ng haemoglobin (Hb)/mL buffer (corresponding to 10 ug Hb/g faeces) was used, representing the standard scenario. We determined the cumulative positivity rate (PR) and the numbers of subjects diagnosed with advanced adenomas (N_AdvAd) and early stage CRC (N_earlyCRC) in the cohort over two rounds of screening (standard scenario) and compared it with hypothetical single-round screening with use of a lower cut-off and omission of the second round (alternative scenario). RESULTS: In the standard scenario, the cumulative (ie, round I and II combined) PR, N_AdvAd and N_earlyCRC were 13%, 180% and 26%, respectively. In alternative scenarios using a cut-off level of respectively >=11 and >=22 ng/HbmL buffer (corresponding to 2 and 4 ug Hb/g faeces), the PRs were 18% and 13%, the N_AdvAd were 180 and 162 and the N_earlyCRC ranged between 22-27 and 22-26. CONCLUSIONS: The diagnostic yield of FIT screening using a lowered positivity threshold in combination with an extended screening interval (up to 5 years) may be similar to conventional FIT strategies. This justifies and motivates further research steps in this direction. PMID- 27006185 TI - The appropriate dose and cost of iron replacement therapy in patients with IBD. PMID- 27006187 TI - The actin-binding ERM protein Moesin directly regulates spindle assembly and function during mitosis. AB - Ezrin-Radixin-Moesin proteins are highly conserved, actin-binding cytoskeletal proteins that play an essential role in microvilli formation, T-cell activation, and tumor metastasis by linking actin filaments to the plasma membrane. Recent studies demonstrated that the only Ezrin-Radixin-Moesin protein of Drosophila melanogaster, Moesin, is involved in mitotic spindle function through stabilizing cell shape and microtubules at the cell cortex. We previously observed that Moesin localizes to the mitotic spindle; hence, we tested for the biological significance of this surprising localization and investigated whether it plays a direct role in spindle function. To separate the cortical and spindle functions of Moesin during mitosis we combined cell biological and genetic methods. We used early Drosophila embryos, in which mitosis occurs in the absence of a cell cortex, and found in vivo evidence for the direct requirement of Moesin in mitotic spindle assembly and function. We also found that the accumulation of Moesin precedes the construction of the microtubule spindle, and the fusiform structure formed by Moesin persists even after the microtubules have disassembled. PMID- 27006186 TI - Study of hepatitis E virus infection of genotype 1 and 3 in mice with humanised liver. AB - OBJECTIVE: The hepatitis E virus (HEV) is responsible for approximately 20 million infections per year worldwide. Although most infected people can spontaneously clear an HEV infection, immune-compromised individuals may evolve towards chronicity. Chronic HEV infection can be cured using ribavirin, but viral isolates with low ribavirin sensitivity have recently been identified. Although some HEV isolates can be cultured in vitro, in vivo studies are essentially limited to primates and pigs. Since the use of these animals is hampered by financial, practical and/or ethical concerns, we evaluated if human liver chimeric mice could serve as an alternative. DESIGN: Humanised mice were inoculated with different HEV-containing preparations. RESULTS: Chronic HEV infection was observed after intrasplenic injection of cell culture-derived HEV, a filtered chimpanzee stool suspension and a patient-derived stool suspension. The viral load was significantly higher in the stool compared with the plasma. Overall, the viral titre in genotype 3-infected mice was lower than that in genotype 1-infected mice. Analysis of liver tissue of infected mice showed the presence of viral RNA and protein, and alterations in host gene expression. Intrasplenic injection of HEV-positive patient plasma and oral inoculation of filtered stool suspensions did not result in robust infection. Finally, we validated our model for the evaluation of novel antiviral compounds against HEV using ribavirin. CONCLUSIONS: Human liver chimeric mice can be infected with HEV of different genotypes. This small animal model will be a valuable tool for the in vivo study of HEV infection and the evaluation of novel antiviral molecules. PMID- 27006188 TI - Does dental undergraduate education and postgraduate training enable intention to provide inhalation sedation in primary dental care? A path analytical exploration. AB - AIM: To examine how quality standards of dental undergraduate education, postgraduate training and qualifications together with confidence and barriers could be utilised to predict intention to provide inhalation sedation. METHODS: All 202 dentists working within primary dental care in NHS Highland were invited to participate. The measures in the questionnaire survey included demographic information, undergraduate education and postgraduate qualifications, current provision and access to sedation service, attitudes towards confidence, barriers and intention to provide inhalation sedation. A path analytical approach was employed to investigate the fit of collected data to the proposed mediational model. RESULTS: One hundred and nine dentists who completed the entire questionnaire participated (response rate of 54%). Seventy-six per cent of dentists reported receiving lectures in conscious sedation during their undergraduate education. Statistically significantly more Public Dental Service dentists compared with General Dental Service (GDS) dentists had postgraduate qualification and Continuing Professional Development training experience in conscious sedation. Only twenty-four per cent of the participants stated that they provided inhalation sedation to their patients. The findings indicated that PDS dentists had higher attitudinal scores towards inhalation sedation than GDS practitioners. The proposed model showed an excellent level of fit. A multigroup comparison test confirmed that the level of association between confidence in providing inhalation sedation and intention varied by group (GDS vs. PDS respondents). Public Dental Service respondents who showed extensive postgraduate training experience in inhalation sedation were more confident and likely to provide this service. CONCLUSION: The quality standards of dental undergraduate education, postgraduate qualifications and training together with improved confidence predicted primary care dentists' intention to provide inhalation sedation. PMID- 27006189 TI - Competing risks of death in women treated with adjuvant aromatase inhibitors for early breast cancer on NCIC CTG MA.27. AB - Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) < 70 years and 2159 (28 %) >= 70 years) were enrolled and followed for median 4.1 years. The 432 deaths comprised 187 (43 %) BC, 66 (15 %) cardiovascular, and 179 (41 %) OT. Five baseline factors were differentially associated with type of death. Older patients had greater BC (p = 0.03), cardiovascular (p < 0.001), and other types (p < 0.001) of mortality. Patients with pre-existing cardiovascular history had worse cardiovascular mortality (p < 0.001); those with worse ECOG performance status had worse OT mortality (p < 0.001). Patients with T1 tumors (p < 0.001) and progesterone receptor positive had less BC mortality (p < 0.001). Fewer BC deaths occurred with node-negative disease (p < 0.001), estrogen receptor-positive tumors (p = 0.001), and without adjuvant chemotherapy (p = 0.005); worse cardiovascular mortality (p = 0.01), with trastuzumab; worse OT mortality, for non-whites (p = 0.03) and without adjuvant radiotherapy (p = 0.003). Overall, 57 % of deaths in MA.27 AI-treated patients were non-breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death. PMID- 27006191 TI - Ethical Case Study of the Researcher-Participant Relationship in End-of-Life Research. AB - Nurse-researchers studying interventions for patients at the end-of-life may become close with participants due to the nature of interactions within the research protocol. In such studies, participants may request further interactions that would constitute clinical care beyond the scope of the protocol. Nurse researchers may feel a conflict of values between their obligation to the research goals and their inclinations and obligations as nurses to care for their patients. Nurse-researchers in this situation aspire to honor the bonds developed through close contact and ensure participants receive standard of care while maintaining standards of research ethics. Analysis of a case and review of applicable concepts in research ethics, including ethical relationships, therapeutic misconception, equipoise, and population vulnerability, are used to develop recommendations regarding the decision parameters for similar cases. PMID- 27006190 TI - Electrophysiological evidence of inhibited orthographic regularity effect on the recognition of real Chinese characters. AB - Orthographic regularity is important for processing Chinese characters. However, the issues how orthographic regularity influences the visual recognition of real Chinese characters and whether common processes related to the potential effect exist between successive (SUCC) and concurrent (CONC) conditions with asynchronous presentation of S1 and S2 are still unclear. In the current study, event-related potential (ERP) technique was adopted to investigate electrophysiological correlates of the orthographic regularity effect. Behaviorally, we found fewer errors and shorter response times for SUCC and CONC conditions compared to simultaneous (SIM) condition with synchronous presentation and disappearance of S1 and S2, which demonstrates similarities between SUCC and CONC and their differences from SIM. We found bilaterally smaller N170 responses for real Chinese characters preceded by false characters compared to real characters, demonstrating that orthographic regularity may inhibit the recognition of real Chinese characters. Additionally, the inhibition effect was present in SUCC and CONC rather than SIM, which shows that smaller N170 responses may have been due to asynchronous presentations of S1 and S2 and common inhibition processes in the SUCC and CONC conditions. PMID- 27006192 TI - Thermodynamic origin of alpha-helix stabilization by side-chain cross-links in a small protein. AB - Peptide cross-linking has been widely explored as a means of constraining short sequences into stable folded conformations, most commonly alpha-helices. The prevailing hypothesis for the origin of helix stabilization is an entropic effect resulting from backbone pre-organization; however, obtaining direct evidence bearing on this hypothesis is challenging. Here, we compare the folding thermodynamics of a small helix-rich protein domain and analogues containing one of three common cross-linking motifs. Analysis of the folding free energy landscapes of linear vs. cyclized species reveal consistent trends in the effect of cyclization on folding energetics, as well as subtle differences based on the chemistry of the cross link. Stabilization in all three systems arises entirely from a reduction in the entropic penalty of folding that more than compensates for an enthalpic destabilization of the folded state. PMID- 27006193 TI - The Relationship Between Cancer Survivors' Socioeconomic Status and Reports of Follow-up Care Discussions with Providers. AB - Socioeconomically disadvantaged cancer survivors are less likely to have adequate follow-up care. In this study, we examined whether socioeconomically disadvantaged survivors are at risk for not having follow-up care discussions with providers, a critical determinant of access to follow-up care and desirable health outcomes. Using the 2011 Medical Expenditure Panel Survey and Experiences with Cancer Survivorship Supplement, we used a binary logit model with sample weights to examine associations between 1320 cancer survivors' socioeconomic status (SES) and reports of follow-up care discussions with providers, controlling for clinical and demographic characteristics. The multivariable model indicated survivors with incomes <=200 % Federal Poverty Level (FPL) had a lower probability of reporting a follow-up care discussion than survivors with incomes >400 % FPL (p < 0.05). Survivors with less than high school education had a lower probability of reporting a discussion than survivors who had a college education or greater (p < 0.05). However, even after controlling for income, survivors with financial hardship had a greater probability of reporting a discussion than survivors with no financial hardship (p < 0.05). Insurance status was not a significant predictor of reporting a discussion (p > 0.05). Socioeconomically disadvantaged cancer survivors are at risk for not having follow-up care discussions with providers, particularly those who report lower income and education. The development of educational interventions targeting provider communication with socioeconomically disadvantaged cancer survivors, and survivors' understanding of the benefits of follow-up care discussions, may promote access to these services. Future research assessing mechanisms underlying relationships between survivors' SES indicators and reports of follow-up care discussions with providers is also warranted. PMID- 27006195 TI - The Relation Between Endocan Levels and Subclinic Atherosclerosis. PMID- 27006194 TI - Genome-wide association analysis of milk yield traits in Nordic Red Cattle using imputed whole genome sequence variants. AB - BACKGROUND: The Nordic Red Cattle consisting of three different populations from Finland, Sweden and Denmark are under a joint breeding value estimation system. The long history of recording of production and health traits offers a great opportunity to study production traits and identify causal variants behind them. In this study, we used whole genome sequence level data from 4280 progeny tested Nordic Red Cattle bulls to scan the genome for loci affecting milk, fat and protein yields. RESULTS: Using a genome-wise significance threshold, regions on Bos taurus chromosomes 5, 14, 23, 25 and 26 were associated with fat yield. Regions on chromosomes 5, 14, 16, 19, 20 and 25 were associated with milk yield and chromosomes 5, 14 and 25 had regions associated with protein yield. Significantly associated variations were found in 227 genes for fat yield, 72 genes for milk yield and 30 genes for protein yield. Ingenuity Pathway Analysis was used to identify networks connecting these genes displaying significant hits. When compared to previously mapped genomic regions associated with fertility, significantly associated variations were found in 5 genes common for fat yield and fertility, thus linking these two traits via biological networks. CONCLUSION: This is the first time when whole genome sequence data is utilized to study genomic regions affecting milk production in the Nordic Red Cattle population. Sequence level data offers the possibility to study quantitative traits in detail but still cannot unambiguously reveal which of the associated variations is causative. Linkage disequilibrium creates difficulties to pinpoint the causative genes and variations. One solution to overcome these difficulties is the identification of the functional gene networks and pathways to reveal important interacting genes as candidates for the observed effects. This information on target genomic regions may be exploited to improve genomic prediction. PMID- 27006196 TI - Room-temperature Y-type emission of perylenes by encapsulation within single walled carbon nanotubes. AB - Fluorescent materials that exhibit large Stokes shifts are useful for suppressing aggregation-caused quenching. Controlling the self-trapped exciton (STE) states in organic dyes with a dimeric structure is one way of tuning Stokes shifts. However, this leads to the spectral broadening of the emissions at room temperature owing to the effects of the surrounding materials on the excited dimers. Here, we demonstrate the effects of confining organic dyes on their optical properties via the encapsulation of perylene molecules within single walled carbon nanotubes. The encapsulated dimeric perylene exhibits fluorescence with large Stokes shifts and long lifetimes through the STE states. In particular, a noticeable emission of dimeric perylene is observed with a vibronic structure at room temperature; this resembles the Y-type emission of dimeric alpha-perylene crystals observed only at low temperatures. The results suggest that the isolation of the excited perylene dimers plays an important role in the occurrence of the room-temperature Y-emission. PMID- 27006197 TI - Homophobia: An Impulsive Attraction to the Same Sex? Evidence From Eye-Tracking Data in a Picture-Viewing Task. AB - INTRODUCTION: Some models suggest that homophobia can be explained as a denied attraction toward same-sex individuals. While it has been found that homophobic men have same-sex attraction, these results are not consistent. AIM: This study drew on the dual-process models to test the assumption that sexual interest in homosexual cues among men high in homophobia will depend on their specific impulses toward homosexual-related stimuli. METHODS: Heterosexual men (N = 38) first completed a scale measuring their level of homonegativity. Then, they performed a manikin task to evaluate their impulsive approach tendencies toward homosexual stimuli (IAHS). MAIN OUTCOMES MEASURES: A picture-viewing task was performed with simultaneous eye-tracking recording to assess participants' viewing time of the visual area of interest (i.e., face and body). RESULTS: IAHS positively predicted the viewing time of homosexual photographs among men with a high score of homonegativity. Men with a high homonegativity score looked significantly longer at homosexual than at heterosexual photographs but only when they had a high IAHS. CONCLUSION: These findings confirm the importance of considering the variability in impulsive processes to understand why some (but not all) men high in homophobia have homosexual interest. These findings reinforce the theoretical basis for elaborating a dual-process model for behaviors in the sexual context. PMID- 27006198 TI - Elevated Galpha11 expression in osteoblast lineage cells promotes osteoclastogenesis and leads to enhanced trabecular bone accrual in response to pamidronate. AB - Osteoblastic cells indirectly induce osteoclastogenesis in the bone microenvironment by expressing paracrine factors such as RANKL and M-CSF, leading to increased bone resorption. These cytokines can be regulated by a variety of intracellular pathways, which include G protein-coupled receptor signaling. To explore how enhanced signaling of the Galphaq/11 pathway in osteoblast lineage cells may mediate osteoclast formation, we cocultured wild-type (WT) preosteoclasts with BMSCs derived from either WT or transgenic mice with osteoblast-specific overexpression of Galpha11 (G11-Tg). G11-Tg cocultures had elevated osteoclast numbers with greater resorptive capacity and increased expression of Rankl, Rankl:Opg (osteoprotegerin), and M-csf compared with cocultures with WT BMSCs. As well, cocultures with G11-Tg BMSCs required a higher concentration of OPG to inhibit osteoclast formation and less angiotensin II to increase osteoclast size. These indicate that G11-Tg osteoblasts drive the increased osteoclast formation and osteopenia seen in G11-Tg mice. Pamidronate treatment of G11-Tg mice restored the trabecular bone loss phenotype, as bone mineral density, bone volume, trabecular number, separation, and expressions of osteoblastic and osteoclastic genes were comparable with WT parameters. These changes were characterized by enhanced accumulation of calcified cartilage in trabecular bone, demonstrating that resorption of the cartilaginous intermediate by osteoclasts is more affected by bisphosphonate treatment in G11-Tg mice. In conclusion, overexpression of Galpha11 in osteoblastic cells promotes osteoclastogenesis by upregulation of Rankl and M-csf and bone loss by increased osteoclast resorption of the trabecular bone and cartilaginous matrix. PMID- 27006199 TI - Skeletal muscle glucose uptake during treadmill exercise in neuronal nitric oxide synthase-MU knockout mice. AB - Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-MU (nNOSMU), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSMU(+/+) and nNOSMU(-/-) mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 +/- 0.6 vs. 15.9 +/- 0.9 min for nNOSMU(+/+) and nNOSMU(-/-), respectively, P > 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSMU(-/-) mice, and exercise increased NOS activity only in nNOSMU(+/+) mice (4.4 +/- 0.3 to 5.2 +/- 0.4 pmol.mg(-1).min(-1), P < 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSMU(-/-) than in nNOSMU(+/+) mice (P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSMU(-/-) mice. In conclusion, nNOSMU is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSMU(-/-) mice may be due to compensatory increases in AMPK activation. PMID- 27006200 TI - Combined high-fat-resveratrol diet and RIP140 knockout mice reveal a novel relationship between elevated bone mitochondrial content and compromised bone microarchitecture, bone mineral mass, and bone strength in the tibia. AB - SCOPE: While resveratrol (RSV) is associated with the prevention of high-fat (HF) diet-induced insulin resistance, the effects on bone health combined with an HF diet is unknown. Therefore, we determined the effect of RSV on bone microarchitecture in the presence of an HF-diet, while also elucidating molecular adaptations within bone that could contribute to bone health status. METHODS AND RESULTS: Male C57BL6 mice were provided control (10% fat) or HF-diet (60% fat) in the presence or absence of RSV for 12 weeks. While RSV prevented HF diet-induced glucose intolerance, HF-RSV compromised tibial microarchitecture, mineral mass, and strength. The compromised outcomes following HF-RSV corresponded with higher markers of osteoclast-activation and bone-resorption (decreased OPG/RANKL ratio; increased cathepsin K), as well as higher markers of tibial mitochondrial content. A molecular model of elevated mitochondrial content (RIP140 knock out (KO) mice) was utilized to determine proof-of-principle that increasing mitochondrial content coincides with decrements in bone health. RIP140 KO mice displayed higher markers of mitochondrial content, and similar to HF-RSV, had compromised bone microarchitecture, lower BMD/strength, and higher markers of osteoclast-activation/bone-resorption. CONCLUSION: These data show that in the presence of an HF-diet, RSV negatively alters bone health, a process associated with increased mitochondrial content and markers of bone resorption. PMID- 27006202 TI - A highly sensitive assay for xanthine oxidoreductase activity using a combination of [(13) C2 ,(15) N2 ]xanthine and liquid chromatography/triple quadrupole mass spectrometry. AB - In this study, we developed a highly sensitive assay for xanthine oxidoreductase (XOR) activity utilizing a combination of [(13) C2 ,(15) N2 ]xanthine and liquid chromatography (LC)/triple quadrupole mass spectrometry (TQMS). In this assay, the amount of [(13) C2 ,(15) N2 ]uric acid (UA) produced by XOR was determined by using LC/TQMS. For this assay, we synthesized [(13) C2 ,(15) N2 ]xanthine as a substrate, [(13) C2 ,(15) N2 ]UA as an analytical standard, and [(13) C3 ,(15) N3 ]UA as an internal standard. The [(13) C2 ,(15) N2 ]UA calibration curve obtained using LC/TQMS under the selected reaction monitoring mode was evaluated, and the results indicated good linearity (R(2) = 0.998, weighting of 1/x(2) ) in the range of 20 to 4000 nM. As a model reaction of less active samples, the XOR activity of serial-diluted mouse plasma was measured. Thereby, the XOR activity of the 1024-fold-diluted mouse plasma was 4.49 +/- 0.44 pmol/100 MUL/h (mean +/- standard deviation, n = 3). This value is comparable to the predicted XOR activity value of healthy human plasma. Hence, this combination method may be used to obtain high-sensitivity measurements required for XOR activity analysis on various organs or human plasma. PMID- 27006201 TI - Effects of Berries Consumption on Cardiovascular Risk Factors: A Meta-analysis with Trial Sequential Analysis of Randomized Controlled Trials. AB - The effects of berries consumption on cardiovascular disease (CVD) risk factors have not been systematically examined. Here, we aimed to conduct a meta-analysis with trial sequential analysis to estimate the effect of berries consumption on CVD risk factors. PubMed, Embase, and CENTRAL were searched for randomized controlled trials (RCTs) that regarding the effects of berries consumption in either healthy participants or patients with CVD. Twenty-two eligible RCTs representing 1,251 subjects were enrolled. The pooled result showed that berries consumption significantly lowered the low density lipoprotein (LDL)-cholesterol [weighted mean difference (WMD), -0.21 mmol/L; 95% confidence interval (CI), 0.34 to -0.07; P = 0.003], systolic blood pressure (SBP) (WMD, -2.72 mmHg; 95% CI, -5.32 to -0.12; P = 0.04), fasting glucose (WMD, -0.10 mmol/L; 95% CI, -0.17 to -0.03; P = 0.004), body mass index (BMI) (WMD, -0.36 kg/m(2); 95% CI, -0.54 to -0.18, P < 0.00001), Hemoglobin A1c (HbA1c) (WMD, -0.20%; 95% CI, -0.39 to -0.01; P = 0.04) and tumor necrosis factor-alpha (TNF-alpha) (WMD, -0.99 rhog/mL; 95% CI, -1.96 to -0.02; P = 0.04). However, no significant changes were seen in other markers. The current evidence suggests that berries consumption might be utilized as a possible new effective and safe supplementary option to better prevent and control CVD in humans. PMID- 27006203 TI - Helical Nano-crystallite (HNC) Phases: Chirality Synchronization of Achiral Bent Core Mesogens in a New Type of Dark Conglomerates. AB - Spontaneous generation of macroscopic homochirality in soft matter systems by self-assembly of exclusively achiral molecules under achiral conditions is a challenging task with relevance for fundamental scientific research and technological applications. Dark conglomerate phases (DC phases), being optically isotropic mesophases composed of conglomerates of macroscopic chiral domains and formed by some non-chiral bent-core mesogens, represent such a case. Here we report two new series of non-symmetric bent-core molecules capable of forming a new type of mirror symmetry broken DC phases. In the synthesized molecules, a bent 4-bromoresorcinol core is connected to a phenyl benzoate wing and an azobenzene wing with or without additional peripheral fluorine substitution. The self-assembly was investigated by DSC, polarizing microscopy, electro-optical studies and XRD. Chiral and apparently achiral DC phases were observed besides distinct types of lamellar liquid crystalline phases with different degree of polar order, allowing the investigation of the transition from smectic to DC phases. This indicates a process in which increased packing density at first gives rise to restricted rotation and thus to growing polar order, which then leads to chirality synchronization, layer frustration and nano-scale crystallization. Topological constraints arising from the twisted packing of helical conformers in lamellar crystals is proposed to lead to amorphous solids composed of helical nano-crystallites with short coherence length (HNC phases). This is considered as a third major type of DC phases, distinct from the previously known liquid crystalline sponge phases and the helical nano-filament phases (HNF phases). Guidelines for the molecular design of new materials capable of self-assembly into these three types of DC phases are proposed. PMID- 27006204 TI - Correction: Dosage compensation can buffer copy-number variation in wild yeast. PMID- 27006205 TI - Complete ligand loss in electron ionization of the weakly bound organometallic tungsten hexacarbonyl dimer. AB - We observed the bare W2(+) metal cation upon electron ionization of the weakly bound W(CO)6 dimer. This metal cation can be only observed due to the fast conversion of the weak cluster bond into a strong covalent bond between the metal moieties. PMID- 27006206 TI - Rapid determination of organochlorine pesticides in fish using selective pressurized liquid extraction and gas chromatography-mass spectrometry. AB - A rapid automated extraction and cleanup method using selective pressurized liquid extraction was developed and validated for 14 organochlorine pesticides in fish. The lipid-removal efficiencies achieved by adding alumina, Florisil, acid treated silica gel, and silica gel to the extraction cell were determined and optimized. In the optimized method, fish (2-3g) was placed above alumina (30 g) in the extraction cell, then the sample was extracted using a 7:3 mixture of hexane and dichloromethane. The method was validated using certified reference materials (NIST SRM 1946 and 1974c), spiked fish, and four lipid-rich fish samples. The mean low- and high-concentration spike recoveries were 91% and 93% with RSD<20%, respectively. Measured concentrations of target OCPs showed good agreement with the certified concentrations in certified reference materials. It suggests the good accuracy and precision of the SPLE method. The proposed method met the most important requirements of an extraction and cleanup procedure, including having a short preparation (cleanup and concentration) time and minimal sample contamination and being able to be automated. PMID- 27006207 TI - Replacing electrolytic iron in a fortification-mix with NaFeEDTA increases both iron and zinc availabilities in traditional African maize porridges. AB - While replacing electrolytic iron with NaFeEDTA in multi-micronutrient fortification-mixes is a popular option, there is no information about the effect on the iron and zinc availabilities in African staple foods. This study evaluated the effects of adding a multi-micronutrient fortification-mix, with no iron, electrolytic iron or NaFeEDTA on the availabilities of iron and zinc from thick and fermented special-grade maize porridges using a Caco-2 cell model. Replacing electrolytic iron with NaFeEDTA significantly (p ? 0.05) increased iron and, importantly zinc, availabilities in both the thick (2.16% vs. 1.45% and 2.51% vs. 2.29%, respectively) and fermented (3.35% vs. 2.66% and 3.04% vs. 2.61%, respectively) porridges. Some of the NaFeEDTA complexes perhaps partially dissociated because of pH changes during simulated digestion, binding with zinc and increasing its availability. NaFeEDTA in a multi-micronutrient fortification mix, added to less refined, high phytate maize meal, would be more effective than electrolytic iron in addressing both iron and zinc deficiencies in low socio economic populations of sub-Saharan Africa. PMID- 27006208 TI - Detection and characterisation of frauds in bovine meat in natura by non-meat ingredient additions using data fusion of chemical parameters and ATR-FTIR spectroscopy. AB - Concerns about meat authenticity are increasing recently, due to great fraud scandals. This paper analysed real samples (43 adulterated and 12 controls) originated from criminal networks dismantled by the Brazilian Police. This fraud consisted of injecting solutions of non-meat ingredients (NaCl, phosphates, carrageenan, maltodextrin) in bovine meat, aiming to increase its water holding capacity. Five physico-chemical variables were determined, protein, ash, chloride, sodium, phosphate. Additionally, infrared spectra were recorded. Supervised classification PLS-DA models were built with each data set individually, but the best model was obtained with data fusion, correctly detecting 91% of the adulterated samples. From this model, a variable selection based on the highest VIPscores was performed and a new data fusion model was built with only one chemical variable, providing slightly lower predictions, but a good cost/performance ratio. Finally, some of the selected infrared bands were specifically associated to the presence of adulterants NaCl, tripolyphosphate and carrageenan. PMID- 27006209 TI - The utilisation of two detectors for the determination of water in honey using headspace gas chromatography. AB - A headspace gas chromatography (HSGC) method was developed for the determination of water content in honey. This method was shown to work with five different honey varieties which had a range of water from 14-16%. It also utilised two different detectors, the thermal conductivity detector (TCD) and the barrier discharge ionisation detector (BID). This method needs no heating pretreatment step as in the current leading method, (i.e. the measurement of refractive index). The solvent-free procedure negates the possibility of solvent-compound interactions as well as solubility limitations, as is common with Karl Fischer titrations. It was also apparent that the classic loss on drying method consistently and substantially produced results that were lower than the correct values. This approach is shown to be rapid, with an analysis time of 4 min when using the TCD detector and under 3 min when utilising the BID detector. HSGC is feasible for the determination of water due to the new PEG-linked geminal dicationic ionic-liquid-coated GC capillary column. In addition it provides accurate and precise determinations of the water content in honey. When using the sensitive BID detector, other trace volatile compounds are observed as well. PMID- 27006210 TI - FTIR-ATR spectroscopy applied to quality control of grape-derived spirits. AB - The Fourier transform infrared (FTIR) spectroscopic method with attenuated total reflectance (ATR) was used for predicting the alcoholic strength, the methanol, acetaldehyde and fusel alcohols content of grape-derived spirits. FTIR-ATR spectrum in the mid-IR region (4000-400 cm(-1)) was used for the quantitative estimation by applying partial least square (PLS) regression models and the results were correlated with those obtained from reference methods. In the developed method, a cross-validation with 50% of the samples was used for PLS analysis along with a validation test set with 50% of the remaining samples. Good correlation models with a great accuracy were obtained for methanol (r(2)=99.4; RPD=12.8), alcoholic strength (r(2)=97.2; RPD=6.0), acetaldehyde (r(2)=98.2; RPD=7.5) and fusel alcohols (r(2) from 97.4 to 94.1; RPD from 6.2 to 4.1). These results corroborate the hypothesis that FTIR-ATR is a useful technique for the quality control of grape-derived spirits, whose practical application may improve the efficiency and quickness of the current laboratory analysis. PMID- 27006212 TI - Effect of low frequency ultrasonication on biochemical and structural properties of chicken actomyosin. AB - Ultrasonication has been introduced as a promising technique to modify the properties of meat and meat products. This study was carried out to investigate the structural and biochemical properties of actomyosin under the influence of ultrasonication at low frequency (20 kHz). CD spectroscopy and second-derivative UV spectra indicated that ultrasonic exposure of 30 min causes significant loss of alpha-helical fraction and marked change in tertiary structure of actomyosin. R-SH content showed maximum amount after 30 min of ultrasonic treatment. Additionally, Ca(2+)-, Mg(2+)- and K(+)(EDTA)-ATPase activities were markedly decreased. No fragmentation was observed in SDS-PAGE while transmission electron micrographs showed complete dispersion of aggregates and arrowhead structure of actomyosin. Given that structural properties are closely associated with functional properties, ultrasonication significantly improves the gelling properties of actomyosin. Scanning electron micrographs showed marked improvement in regular three-dimensional networks of actomyosin gels. Concurrently, significant increase in water-holding capacity was also observed. PMID- 27006211 TI - Selective capture of most celiac immunogenic peptides from hydrolyzed gluten proteins. AB - The available immunomethods for gluten quantitation could underestimate or overestimate the net immunoactivity of foods and beverages if the chosen analytical antibody is not specific to the relevant gluten immunogenic peptides (GIP). Accurate detection of the most active GIP is desirable to assess the potential celiac toxicity of food. We evaluated the capacity of the G12 monoclonal antibody for selectively depleting GIP in samples from two different gluteomes. Samples of hydrolyzed gliadin from wheat and a barley beer were used. The input (starting peptide digest of prolamins), the flow-through (unbound peptides), and the output (captured peptides) were analyzed by G12 and R5 competitive ELISA as well as by stimulation assays of T-cells from celiac patients. Most of the GIP were retained by the G12-agarose and represented the largest part of the immunogenicity of the gluten peptidome. G12 immunodepletion experiments with hydrolyzed gluten showed that this antibody reacted with those with the highest immunoactivity for celiac patients. PMID- 27006213 TI - Homostachydrine (pipecolic acid betaine) as authentication marker of roasted blends of Coffea arabica and Coffea canephora (Robusta) beans. AB - The occurrence of pipecolic acid betaine (homostachydrine) and its biosynthetic precursor N-methylpipecolic acid was detected for the first time in green coffee beans of Robusta and Arabica species. The analyses were conducted by HPLC-ESI tandem mass spectrometry and the metabolites identified by product ion spectra and comparison with authentic standards. N-methylpipecolic acid was found at similar levels in green coffee beans of Robusta and Arabica, whereas a noticeable difference of homostachydrine content was observed between the two green coffee bean species. Interestingly, homostachydrine content was found to be unaffected by coffee bean roasting treatment because of a noticeable heat stability, a feature that makes this compound a candidate marker to determine the content of Robusta and Arabica species in roasted coffee blends. To this end, a number of certified pure Arabica and Robusta green beans were analyzed for their homostachydrine content. Results showed that homostachydrine content was 1.5+/ 0.5mg/kg in Arabica beans and 31.0+/-10.0mg/kg in Robusta beans. Finally, to further support the suitability of homostachydrine as quality marker of roasted blends of Arabica and Robusta coffee beans, commercial samples of roasted ground coffee blends were analyzed and the correspondence between the derived percentages of Arabica and Robusta beans with those declared on packages by manufacturers was verified. PMID- 27006214 TI - Metabolomics analysis of shucked mussels' freshness. AB - In this work a NMR metabolomics approach was applied to analyze changes in the metabolic profile of the bivalve mollusk Mytilus galloprovincialis upon storage at 0 degrees C and 4 degrees C for 10 and 6 days, respectively. The most significant microbial groups involved in spoilage of mussels were also investigated. The time-related metabolic signature of mussels was analysed by Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) which revealed a clear discrimination between the fresh samples and those stored at 0 degrees C and 4 degrees C. The results evidenced a noticeable increase in acetate, lactate, succinate, alanine, branched chain amino acids, trimethylamine and a progressive decline of osmolytes like betaine, homarine and taurine during storage. Exploration of the correlations of these metabolites with microbial counts suggested their use as potential biomarkers of spoilage. The results support the use of NMR metabolomics as a valuable tool to provide information on seafood freshness. PMID- 27006215 TI - Inline roasting hyphenated with gas chromatography-mass spectrometry as an innovative approach for assessment of cocoa fermentation quality and aroma formation potential. AB - Today, the cocoa industry is in great need of faster and robust analytical techniques to objectively assess incoming cocoa quality. In this work, inline roasting hyphenated with a cooled injection system coupled to a gas chromatograph mass spectrometer (ILR-CIS-GC-MS) has been explored for the first time to assess fermentation quality and/or overall aroma formation potential of cocoa. This innovative approach resulted in the in-situ formation of relevant cocoa aroma compounds. After comparison with data obtained by headspace solid phase micro extraction (HS-SPME-GC-MS) on conventional roasted cocoa beans, ILR-CIS-GC-MS data on unroasted cocoa beans showed similar formation trends of important cocoa aroma markers as a function of fermentation quality. The latter approach only requires small aliquots of unroasted cocoa beans, can be automatated, requires no sample preparation, needs relatively short analytical times (<1h) and is highly reproducible. PMID- 27006216 TI - Characterization of catechin-alpha-lactalbumin conjugates and the improvement in beta-carotene retention in an oil-in-water nanoemulsion. AB - The goal of this study was to prepare and characterize alpha-lactalbumin (ALA) catechin conjugates as a novel emulsifier in improving the retention of beta carotene (BC) in nanoemulsions via a free radical method. Covalent modification was observed and at least one catechin molecule was binding with ALA according to ESI-MS results. Far-UV CD indicated that the secondary structure of ALA was changed after conjugation. The Z-average particle diameters of nanoemulsions stabilized with ALA and ALA-catechin conjugates were 158.8 and 162.7 nm, respectively. The increase of mean particle size and the degradation of BC at 50 degrees C were both larger than at 25 degrees C during 30 days storage. BC retention stabilized with ALA-catechin conjugates was appreciably greater than ALA (control), which was attributed to the increase of ALA's radicals-scavenging and free metal ion binding ability after grafting with catechin. The chemical antioxidant activities of ALA-catechin conjugates were increased with increasing concentrations from 0.1 to 1.0mg/ml. In general, labile phytochemicals, like BC, can be protected against oxidation during storage by proteins-polyphenols conjugates without any side effects. PMID- 27006217 TI - Biodetection of potential genotoxic pollutants entering the human food chain through ashes used in livestock diets. AB - Ash derived from energy generation is used as a source of minerals in livestock feeds. The microbial biosensor recApr-Luc2 was built to detect genotoxic hazard in recycled ash. Escherichia coli SOS gene (recA, lexA, dinI and umuC) expression in response to cisplatin-induced DNA damage led to the selection of the recA promoter. The biosensor required functional RecA expression to respond to genotoxic heavy metals (Cr>Cd~Pb), and polluted ash induced a strong recApr-Luc2 response. In human liver and intestinal cells, heavy metals induced acute toxicity (Cr>Cd>Pb) at concentrations sufficient to activate recApr-Luc2. Cytostatic effects, including genotoxicity, were cell- and metal-dependent, apart from Cr. In agreement with the recApr-Luc2 bioassay, Cr had the strongest effect in all cells. In conclusion, recApr-Luc2 could be useful for evaluating the genotoxic risk of pollutants present in ash that might be concentrated in animal products and, thus, entering the human food chain. PMID- 27006218 TI - Lipidomic profiling of dried seahorses by hydrophilic interaction chromatography coupled to mass spectrometry. AB - Dried seahorse is a precious raw food material for cooking soups. In this study, a lipidomics strategy using the techniques of solid-phase extraction (SPE) and hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-QTOF/MS) was developed for extraction, visualization, and quantification of phospholipids in dried seahorses. The parameters of SPE were optimized, and 1 mL of sample and chloroform/methanol (1:2, v/v) were found to be the best loading volume and eluting solvent, respectively. Afterwards, each phospholipid class was successfully separated on a HILIC column and analyzed by mass spectrometry. A total of 50 phospholipid molecular species were identified and determined, including 15 phosphatidylcholines (PCs), 14 phosphatidylethanolamines (PEs), 12 phosphatidylinositols (PIs) and 9 phosphatidylserines (PSs). In comparison to previously methods, this strategy was robust and efficient in extraction, characterization, and determination of phospholipids. The dried seahorse was found to contain large amounts of polyunsaturated fatty acyl phospholipids which are beneficial to human health. PMID- 27006219 TI - Structural, functional, and antioxidant properties of water-soluble polysaccharides from potatoes peels. AB - Water-soluble polysaccharides were extracted from potato peel waste (PPW). The structure of the polysaccharides from PPW (PPPW) was examined by means of Fourier transform-infrared spectroscopy (FT-IR) analysis, X-ray diffractometry (XRD) and gas chromatography-mass spectrometry (GC-MS). The results suggest that the extracted polysaccharides form a semi-crystalline polymer constituted essentially of the functional groups CO, CH and OH. Acid hydrolysis of this polymer yielded glucose (76.25%) as the dominant sugar functional properties (water holding capacity: WHC, oil holding capacity: OHC, foaming, and emulsion properties) of this polymer were studied. The PPPW showed interesting water-holding and fat binding capacities which were 4.097 +/- 0.537 g/g and 4.398 +/- 0.04 g/g, respectively. In addition, it presented good foaming and emulsion properties. The antioxidant activity of this polymer was also studied and revealed that the polysaccharides showed interesting 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity (IC50 PPPW=11.578 mg/mL), reducing power and beta-carotene bleaching inhibition activities, and also a strong ABTS radical scavenging activity (IC50 PPPW=2mg/mL). Overall, the results suggest that the polysaccharide is a promising source of natural antioxidants and can be used as additive in food, pharmaceutical and cosmetic preparations. PMID- 27006220 TI - Occurrence of rhodamine B contamination in capsicum caused by agricultural materials during the vegetation process. AB - This paper reports on the environmental rhodamine B (RhB) contamination in capsicum caused by agricultural materials during the vegetation process. Ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to detect 64 capsicum samples from China, Peru, India and Burma. Results demonstrated that RhB was found in all samples at low concentrations (0.11-0.98 MUg/kg), indicating RhB contamination in capsicums is probably a ubiquitous phenomenon. In addition, studies into soils, roots, stems and leaves in Handan of Hebei province, China showed that the whole ecologic chain had been contaminated with RhB with the highest levels in leaves. The investigation into the agricultural environment in Handan of Hebei province and Korla of Xinjiang province, China demonstrated that the appearances of RhB contamination in the tested capsicums are mainly due to the agricultural materials contamination. The study verified that environmental contamination should be an important origin for the RhB contamination in capsicum fruits. PMID- 27006221 TI - Determination of sugars, organic acids, aroma components, and carotenoids in grapefruit pulps. AB - The composition and content of sugars, organic acids, volatiles and carotenoids, in the pulps of six grapefruit cultivars, were examined by HPLC and GC-MS. The results showed that sucrose was the dominant sugar in grapefruit, making up 40.08 59.68% of the total sugars, and the ratio of fructose to glucose was almost 1:1. Citric acid was the major organic acid and represented 39.10-63.55% of the total organic acids, followed by quininic acid. The ratios of individual sugars and organic acids play an important role in grapefruit taste determination. Monoterpenes and sesquiterpenes were the predominant volatiles in grapefruit, in particular d-limonene and caryophyllene. Caryophyllene, alpha-humulene, humulen (v1), beta-linalool and tert-butyl 2-methylpropanoate are the characteristic aroma compounds of grapefruit. Although beta-carotene is the primary carotenoid in grapefruit, the pulp color is mainly determined by the ratios of zeaxanthin, beta-cryptoxanthin and lycopene. Our results provide the first complete chemical characterization of the taste, aroma and color of grapefruit. PMID- 27006222 TI - CO2 processing and hydration of fruit and vegetable tissues by clathrate hydrate formation. AB - CO2 hydrate can be used to preserve fresh fruits and vegetables, and its application could contribute to the processing of carbonated frozen food. We investigated water transformation in the frozen tissue of fresh grape samples upon CO2 treatment at 2-3 MPa and 3 degrees C for up to 46 h. Frozen fresh bean, radish, eggplant and cucumber samples were also investigated for comparison. X ray diffraction indicated that after undergoing CO2 treatment for several hours, structure I CO2 hydrate formed within the grape tissue. Phase-contrast X-ray imaging using the diffraction-enhanced imaging technique revealed the presence of CO2 hydrate within the intercellular spaces of these tissues. The carbonated produce became effervescent because of the dissociation of CO2 hydrate through the intercellular space, especially above the melting point of ice. In addition, suppressed metabolic activity resulting from CO2 hydrate formation, which inhibits water and nutrient transport through intercellular space, can be expected. PMID- 27006223 TI - Utilization of interfacial engineering to improve physicochemical stability of beta-carotene emulsions: Multilayer coatings formed using protein and protein polyphenol conjugates. AB - The impact of lactoferrin (LF)-chlorogenic acid (CA) and (-)-Epigallocatechin-3 gallate (EGCG) conjugates on the physicochemical properties of beta-carotene emulsions was investigated. Formation of lactoferrin-polyphenol conjugates, which was confirmed by SDS-PAGE, caused changes in the structure and nature of lactoferrin. Based on layer-by-layer electrostatic deposition, beta-carotene bilayer emulsions were prepared by lactoferrin and lactoferrin-polyphenol conjugates at pH 7.0. The physicochemical properties of primary and secondary emulsions were evaluated and the results suggested that LF-polyphenol conjugates stabilized primary and secondary emulsions exhibited better emulsifying properties and improved physical stability of beta-carotene bilayer emulsions under freeze-thaw, ionic strength and thermal treatments. In addition, the lactoferrin-polyphenol conjugates could effectively enhance chemical stability of beta-carotene in oil-in-water emulsions against heat treatment and ultraviolet light exposure, and the least degradation of beta-carotene occurred in LF-EGCG conjugate-stabilized primary emulsion. The interfacial engineering technology utilized in this study may lead to the formation of emulsions with improved physicochemical and functional performance. PMID- 27006224 TI - Optimization by response surface methodology of lutein recovery from paprika leaves using accelerated solvent extraction. AB - In this study, we used response surface methodology (RSM) to optimize the extraction conditions for recovering lutein from paprika leaves using accelerated solvent extraction (ASE). The lutein content was quantitatively analyzed using a UPLC equipped with a BEH C18 column. A central composite design (CCD) was employed for experimental design to obtain the optimized combination of extraction temperature ( degrees C), static time (min), and solvent (EtOH, %). The experimental data obtained from a twenty sample set were fitted to a second order polynomial equation using multiple regression analysis. The adjusted coefficient of determination (R(2)) for the lutein extraction model was 0.9518, and the probability value (p=0.0000) demonstrated a high significance for the regression model. The optimum extraction conditions for lutein were temperature: 93.26 degrees C, static time: 5 min, and solvent: 79.63% EtOH. Under these conditions, the predicted extraction yield of lutein was 232.60 MUg/g. PMID- 27006225 TI - Bioavailability assessment of essential and toxic metals in edible nuts and seeds. AB - Bioavailability of essential and toxic metals in edible nuts and seeds has been assessed by using an in vitro dialyzability approach. The samples studied included walnuts, Brazil nuts, Macadamia nuts, pecans, hazelnuts, chestnuts, cashews, peanuts, pistachios and seeds (almond, pine, pumpkin and sunflower). Metals were measured by inductively coupled plasma-mass spectrometry in dialyzates and also in samples after a microwave assisted acid digestion pre treatment. Low dialyzability percentages were found for Al, Fe and Hg; moderate percentages were found for Ba, Ca, Cd, Co, Cu, K, Li, Mg, Mn, Mo, P, Pb, Se, Sr, Tl and Zn; and high dialyzability ratios were found for As, Cr and Ni. The highest dialyzability percentages were found in raw chestnuts and raw hazelnuts. Metal dialyzability was found to be negatively affected by fat content. Positive correlation was found between carbohydrate content and metal dialyzability ratios. Protein and dietary fibre content did not influence metal bioavailability. Predicted dialyzability for some metals based on fat and protein content could also be established. PMID- 27006226 TI - Stability evaluation of lutein nanodispersions prepared via solvent displacement method: The effect of emulsifiers with different stabilizing mechanisms. AB - The stability of lutein nanodispersions was evaluated during storage and when exposed to different environmental conditions. Lutein nanodispersions were prepared using Tween 80, sodium dodecyl sulfate (SDS), sodium caseinate (SC) and SDS-Tween 80 as the emulsifiers. During eight weeks of storage, all samples showed remarkable physical stability. However, only the SC-stabilized nanodispersion showed excellent chemical stability. Under different environmental conditions, the nanodispersions exhibited a varied degree of stability. All nanodispersions showed constant particle sizes at temperatures between 30 and 60 degrees C. However, at pH 2-8, only the SC-stabilized nanodispersion was physically unstable. The addition of NaCl (300-400 mM) only caused flocculation in nanodispersion stabilized by SDS-Tween 80. All nanodispersions were physically stable when subjected to different centrifugation speeds. Only Tween 80 stabilized nanodispersion was stable against the effect of freeze-thaw cycles (no phase separation observed). In this study, there was no particular emulsifier that was effective against all of the environmental conditions tested. PMID- 27006227 TI - Inhibitory effects of chickpea and Tribulus terrestris on lipase, alpha-amylase and alpha-glucosidase. AB - The total saponin content and its in vitro bioaccessibilities in Tribulus terrestris and chickpea were determined by a static in vitro digestion method (COST FA1005 Action INFOGEST). Also, in vitro inhibitory effects of the chosen food samples on lipid and starch digestive enzymes were determined by evaluating the lipase, alpha-amylase and alpha-glucosidase activities. The tested T. terrestris and chickpea showed inhibitory activity against alpha-glucosidase (IC50 6967 +/- 343 and 2885 +/- 85.4 MUg/ml, respectively) and alpha-amylase (IC50 343 +/- 26.2 and 167 +/- 6.12 MUg/ml, respectively). The inhibitory activities of T. terrestris and chickpea against lipase were 15.3 +/- 2.03 and 9.74 +/- 1.09 MUg/ml, respectively. The present study provides the first evidence that these food samples (T. terrestris, chickpea) are potent inhibitors of key enzymes in digestion of carbohydrates and lipids in vitro. PMID- 27006228 TI - Effect of germination on lignan biosynthesis, and antioxidant and antiproliferative activities in flaxseed (Linum usitatissimum L.). AB - Flaxseed is one of the richest seed sources of lignan and other bioactive compounds. The present study characterized lignan biosynthesis and potential health benefits in flaxseeds during 10-day germination. The transcription levels of lignan biosynthesis, along with variation of bioactivities, including cellular antioxidant activity and antiproliferative activity of flaxseed sprouts during germination, were studied. The results showed that 8-day germination brought about a 6.3-fold increase in secoisolariciresinol diglucoside and 4.5-fold increase in secoisolariciresinol compared to ungerminated flaxseeds. The highest amount of total phenolics and total flavonoids were found in 10-day geminated flaxseed, namely a 5.6-fold and 55-fold increase compared to ungerminated flaxseed. Transcription analysis revealed that five key-encoding genes in the lignan biosynthetic pathway were up-regulated during germination. Furthermore, the highest antioxidant and antiproliferative activities were found on day 10. These findings suggest that germination for 8-10 days leads to optimal lignan production and potential health benefits if incorporated into the human diet. PMID- 27006229 TI - Identification and quantification of phosphatidylinositol in infant formulas by liquid chromatography-mass spectrometry. AB - Using LC-LTQ-Orbitrap MS we were able to identify 10 major phosphatidylinositol (PI) species present in 32 infant formulas (IF) collected from Australia, Europe and the USA. Based on the species fingerprint, the 32 formulas can be classified into several distinct groups by PCA analysis; this grouping pattern reflects origin and the label information of the formulas. The total content of all PI species was determined by LC-Triple Quadrupole MS in negative MRM mode using external standard calibration. The content of PI showed large variation between formulas and was very high in certain cases, which is believed to be related to the use of soybean lecithin in these products. Our study indicates that the content and speciation of PIs have significant contribution to the total amount of inositol in all 32 products surveyed; this contribution may be important for the fine nutritional profile and biological functions of IF products. PMID- 27006230 TI - Use of purple durum wheat to produce naturally functional fresh and dry pasta. AB - In this study, the effects of different milling procedures (roller-milling vs. stone-milling) and pasta processing (fresh vs. dried spaghetti), and cooking on the antioxidant components and sensory properties of purple durum wheat were investigated. Milling and pasta processing were performed using one purple and one conventional non-pigmented durum wheat genotypes, and the end-products were compared with commercial pasta. The results show that the stone milling process preserved more compounds with high health value (total fibre and carotenoids, and in the purple genotype, also anthocyanins) compared to roller-milling. The drying process significantly (p<0.05) reduced the content of anthocyanins (21.42 MUg/g vs. 46.32 MUg/g) and carotenoids (3.77 MUg/g vs. 4.04 MUg/g) with respect to the pasteurisation process involved in fresh pasta production. The sensory properties of pasta from the purple genotype did not significantly differ from commercial wholemeal pasta, and its in vitro glycemic index was even lower. Thus, it is possible to consider this genetic material as a good ingredient for the production of functional foods from cereals naturally rich in bioactive compounds. PMID- 27006231 TI - Lipidomics to analyze the influence of diets with different EPA:DHA ratios in the progression of Metabolic Syndrome using SHROB rats as a model. AB - The role of specific proportions of omega-3 EPA and DHA, in the modulation of inflammation and oxidative stress markers associated to the progression of Metabolic Syndrome was investigated. Potential inflammatory eicosanoids and docosanoids were discussed together to biomarkers of CVD, obesity, inflammation and oxidative stress in an animal model of metabolic disorders. Results evidenced a noteworthy health effect of 1:1 and 2:1 EPA:DHA proportions over 1:2 EPA:DHA based diets through a down-regulation in the production of strong pro inflammatory omega-6 eicosanoids, a decrement of biomarkers of oxidative stress, and a modulation of fatty acid desaturase activities and plasma and membrane PUFAs towards greater anti-inflammatory profiles. Outcomes contribute to the general knowledge on the health benefits of marine lipids and their role on the progress of MetS, inflammation and oxidative stress. Results shed light on controversial protective mechanisms of EPA and DHA to better design dietary interventions aimed at reducing MetS. PMID- 27006232 TI - Phytochemicals from Camellia nitidissima Chi inhibited the formation of advanced glycation end-products by scavenging methylglyoxal. AB - The objective of this study was to investigate the inhibitory effects of Camellia nitidissima Chi (CNC) on the advanced glycation end-product (AGE) formation. CNC was extracted with ethanol and further separated into dichloromethane, ethyl acetate, n-butanol, and water soluble fractions. Ethyl acetate fraction had the highest total phenolic and quercetin content compared with other fractions. Sixteen phenolic compounds were identified using HPLC Triple TOF MS/MS. Bovine serum albumin (BSA)-glucose assay showed that dichloromethane and ethyl acetate fraction inhibited AGE formation by 88.1% and 87.5% at 2.5mg/mL. BSA methylglyoxal assay showed that ethyl acetate fraction inhibited 54.1% AGE formation while dichloromethane fraction inhibited 28.1%. Over 96.0% of methylglyoxal was scavenged by different fractions within 12h. Both mono- and di methylglyoxal quercetin adducts were identified after incubating quercetin with methylglyoxal using HPLC-ESI-MS(n). The results in this study suggest that CNC extracts inhibited AGEs formation in part through scavenging methylglyoxal by phenolic compounds. PMID- 27006233 TI - The impact of hop bitter acid and polyphenol profiles on the perceived bitterness of beer. AB - Thirty-four commercial lager beers were analysed for their hop bitter acid, phenolic acid and polyphenol contents. Based on analytical data, it was evident that the beers had been produced using a range of different raw materials and hopping practices. Principal Components Analysis was used to select a sub-set of 10 beers that contained diverse concentrations of the analysed bitter compounds. These beers were appraised sensorially to determine the impacts of varying hop acid and polyphenolic profiles on perceived bitterness character. Beers high in polyphenol and hop acid contents were perceived as having 'harsh' and 'progressive' bitterness, whilst beers that had evidently been conventionally hopped were 'sharp' and 'instant' in their bitterness. Beers containing light stable hop products (tetrahydro-iso-alpha-acids) were perceived as 'diminishing', 'rounded' and 'acidic' in bitterness. The hopping strategy adopted by brewers impacts on the nature, temporal profile and intensity of bitterness perception in beer. PMID- 27006234 TI - Detection of antibacterial activity of an enzymatic hydrolysate generated by processing rainbow trout by-products with trout pepsin. AB - Trout by-product hydrolysates, generated using trout pepsin, were characterized and studied in terms of their antibacterial effects against food contaminants and fish farming pathogens. After a hydrolysis time of 25 min, the hydrolysates demonstrated inhibitory activity against several gram-positive and gram-negative bacteria. The degree of hydrolysis (DH) was found to exert a considerable influence on antibacterial activity, with a significant increase in the observed inhibitory effect at the beginning of hydrolysis. The highest antibacterial activity was obtained at a DH of 30% (enzyme/protein ratio 0.04 U/mg of protein, enzyme activity 6.5 U/mg protein, hydrolysis conditions 37 degrees C, pH 3.0). The highest antibacterial activity detected was against the fish farming bacteria Flavobacterium psychrophilum and Renibacterium salmoninarum, with minimal inhibition concentrations of 2mg/ml and 5mg/ml, respectively. The amino acid determination of the hydrolysate (DH 30%) revealed that lysine, leucine, alanine, arginine, glycine, aspartic acid and glutamic acid residues represented the major amino acids. PMID- 27006235 TI - Immunoreactivity, sensory and physicochemical properties of fermented soy protein isolate. AB - The effect of induced liquid state fermentation (Bacillus subtilis, Rhizopus oryzae, Saccharomyces cerevisiae, Lactobacillus helveticus) on the immunoreactivity, physicochemical and sensory properties of soy protein isolate (SPI) was studied. L. helveticus revealed the most abundant reduction in terms of immunoreactivity within soluble protein fractions, up to 100%, which could be measured by in vitro sandwich ELISA using mouse monoclonal anti-Glym5 antibodies (mAbs). Almost no binding was found in western blot analysis using mouse monoclonal mAbs and sera from soy sensitive individuals. Fermentation increased water- and oil-binding capacity as well as protein solubility at pH 4.0. Foaming activity was nearly doubled compared to non-fermented SPI. A decreased emulsifying capacity, foaming density, and quantity of soluble proteins at pH 7.0 were observed. Principal component analysis (PCA) confirmed decreased bitter and beany off-flavors of fermented samples compared to non-fermented SPI. Consequently, fermentation might be a promising method to produce tasty low allergen food ingredients with good physicochemical properties. PMID- 27006236 TI - Salal (Gaultheria shallon) and aronia (Aronia melanocarpa) fruits from Orkney: Phenolic content, composition and effect of wine-making. AB - The polyphenol content and composition of salal and aronia fruits from plants established in Orkney was examined. The composition of the salal fruits has not previously been recorded, and they contained anthocyanins, flavonols, hydroxycinnamates and proanthocyanins. The aronia fruits contained anthocyanins, hydroxycinnamates and flavonols as previously described. Although salal fruits had half the anthocyanin content of aronia fruits, salal wine had higher anthocyanin content, probably due to the relative stability of diglycoside pentose anthocyanins. The wines contained components suggestive of anthocyanin and flavonol degradation, but there was no consistent pattern to stability within phenolic sub-classes. Indeed, the wine made from equal amounts of salal and aronia fruits had patterns of recovery of individual phenolic components which could not be predicted from recoveries in wines from single fruits. This strongly suggests that stability of individual phenolic constituents during wine-making is influenced by the presence and relative stability of other components. PMID- 27006237 TI - Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans. AB - Hydroxytyrosol (HT) and its derivatives in olive oil protect low-density lipoproteins (LDL) against oxidation. Biscuits could be a convenient alternative to broaden consumers' choice of HT-rich foods, although the biscuit matrix could affect HT bioavailability. We performed a crossover, randomized, double-blind study to evaluate HT bioavailability in HT-enriched biscuits (HT-B) versus non enriched biscuits (C-B), and the effects on oxidative postprandial status. On two separate days, 13 subjects consumed 30 g of C-B or HT-B (5.25mg HT) after overnight-fasting. Blood and urine were collected at different intervals and analysed by LC-MS-QToF. After HT-B consumption, plasma metabolites peaked between 0.5 and 1h and were extensively excreted in urine. HT-sulphate and 3,4 dihydroxyphenylacetic acid (DOPAC)-sulphate were the main metabolites, followed by DOPAC and homovanillic acid (HVA). HT-glucuronide, DOPAC-glucuronide, HVA glucuronide and HVA-sulphate were also detected. Postprandial oxidised-LDL concentrations decreased with HT-B. HT is a promising functional ingredient and, in biscuits, it is highly bioavailable and lowers postprandial oxidised-LDL levels. PMID- 27006238 TI - Internal browning disorder of eight pear cultivars affected by bioactive constituents and enzyme activity. AB - Internal browning (IB) is a disorder in pears that is frequently observed in some cultivars. The present research was carried out to study biochemical changes and IB disorder of pear fruit during storage and ripening. Eight pear cultivars harvested and stored at 1 degrees C up to 90 days. IB incidence, some bioactive compounds, polyphenol oxidase (PPO), peroxidase (POX), and superoxide dismutase (SOD) enzymes activities were measured during storage. IB increased during storage time but the susceptibility of cultivars was different. The ascorbic acid (AA), antioxidant capacity (AC) and SOD activity decreased while POX activity increased during storage but the rate of changes were different in studied cultivars. Total phenol (TP) and total flavonoid (TF) average content varied among pear cultivars and the highest TP and TF were observed in 'Bakhi' cultivars during storage. Fruit IB had positive correlation with the PPO activity, but negative correlation with TP, AC and AA. PMID- 27006239 TI - Elucidation of the role of oleosin in off-flavour generation in soymeal through supercritical CO2 and biotic elicitor treatments. AB - Defatting soybean by sophisticated oil extraction method utilising supercritical CO2 resulted in a significant decrease in the residual phospholipids (PLs) compared with soymeal obtained by conventional cold percolation method utilising hexane as the extraction solvent. Interestingly, the levels of residual PLs showed a proportionate relationship with thiobarbituric acid (TBA) number, an indicator of lipid peroxidation responsible for off-flavour generation. Furthermore, two oleosins (18 and 24 kDa) were isolated from the oil bodies extracted from soybean seeds and positively characterised for phospholipase A2 (PLA2) activity, suggesting their plausible involvement in off-flavour generation in soymeal. The treatment of soybean seeds, before oil extraction, with different concentrations of biotic elicitors such as chitosan and jasmonic acid also significantly reduced the levels of residual PLs as well as the TBA number. The biotic elicitor treatment could thus prove to be an important strategy for the reduction of off-flavour in protein-rich soymeal. PMID- 27006240 TI - Whole genome sequence analysis of unidentified genetically modified papaya for development of a specific detection method. AB - Identification of transgenic sequences in an unknown genetically modified (GM) papaya (Carica papaya L.) by whole genome sequence analysis was demonstrated. Whole genome sequence data were generated for a GM-positive fresh papaya fruit commodity detected in monitoring using real-time polymerase chain reaction (PCR). The sequences obtained were mapped against an open database for papaya genome sequence. Transgenic construct- and event-specific sequences were identified as a GM papaya developed to resist infection from a Papaya ringspot virus. Based on the transgenic sequences, a specific real-time PCR detection method for GM papaya applicable to various food commodities was developed. Whole genome sequence analysis enabled identifying unknown transgenic construct- and event-specific sequences in GM papaya and development of a reliable method for detecting them in papaya food commodities. PMID- 27006241 TI - Intra-oral adsorption and release of aroma compounds following in-mouth wine exposure. AB - Wine "after-odour" defined as the long lasting aroma perception that remains after wine swallowing is an outstanding characteristic in terms of wine quality but a relatively unstudied phenomenon. Among the different parameters that might affect wine after-odour, the adsorption of odorants by the oral mucosa could be important but has been little explored. In this work, the impact of the chemical characteristics of aroma compounds on intra-oral adsorption was assessed by an in vivo approach that determined the amounts of odorants remaining in expectorated wine samples. In addition, the subsequent aroma release after in-mouth wine exposure was studied by means of intra-oral SPME/GC-MS using three different panellists. Oral adsorption of the aroma compounds added to the wines ranged from 6% to 43%, depending on their physicochemical characteristics. A progressive intra-oral aroma decrease at different decay rates depending on compound type and panellist was also found. The strength of the aroma-oral mucosa interactions seems to explain these results more than the amount of compound adsorbed by the oral mucosa. PMID- 27006242 TI - Effect of dietary phosphorus levels on meat quality and lipid metabolism in broiler chickens. AB - To analyze the influence of dietary phosphorus (P) levels on meat quality and lipid metabolism, a 42-day feeding experiment (P deficient group; normal group; high P level groups of H1 and H2, respectively) using 100 one-day-old broilers was conducted. Results demonstrated that the quality of broiler chicken meat in deficient or high P groups decreased relative to the normal group. High P diets resulted in increased lightness, redness values, shear forces and decreased fatty acid contents and intramuscular fat content in breast meat (p<0.01). Compared with normal group, lower malic enzyme activity, higher fatty acid synthase and AMP-activated protein kinase activities were observed in the treatment groups (p<0.05). Chickens fed with normal diets had the lowest serum total cholesterol and triglyceride levels which differed from that of other treatments (p<0.05). High-P diets significantly decreased the lipid accumulation in the liver (p<0.01), whereas phosphorus levels in breast meat increased significantly (p<0.01). It can be concluded that deficient or higher P levels could affect meat quality and expression of indicators on lipid metabolism of broiler chickens. PMID- 27006243 TI - Microbiological characterisation and volatiles profile of model, ex-novo, and traditional Italian white wheat sourdoughs. AB - The interplay of sourdough microbiology and generated volatile compounds that define its sensory characteristics was studied. In order to detail the flavour generating potential of microorganisms, eight single-strain dough fermentations were studied, four of them never investigated before. Moreover, for the first time, both ex-novo and traditional wheat sourdoughs were investigated and compared to chemically acidified dough. HS-SPME-GC-MS was used to sample and analyse volatile compounds, some of which have never been detected before in sourdoughs. Alcohols, esters, carbonyl compounds, and acids mainly characterised the volatile profiles. Different sourdough microbiota resulted in different volatile profiles. PCA indicated that samples could be clustered according to their specific microbiota. Production of aroma compounds was strain-specific, confirming previous findings. This study can contribute to the management of desirable features and differentiate specialty products, as well as selecting new, suitable, sourdoughs after microbial screening. PMID- 27006244 TI - Dental implant surface chemistry and energy alter macrophage activation in vitro. AB - OBJECTIVES: To determine the effects of dental implant surface chemistry and energy on macrophage activation in vitro. MATERIALS AND METHODS: Disks made from two clinically used implant materials (titanium [Ti], titanium zirconium alloy [TiZr]) were produced with two different surface treatments (sandblast/acid-etch [SLA], hydrophilic-SLA [modSLA]). Surface roughness, energy, and chemistry were characterized. Primary murine macrophages were isolated from 6- to 8-week-old male C57Bl/6 mice and cultured on test surfaces (Ti SLA, TiZr SLA, Ti modSLA, TiZr modSLA) or control tissue culture polystyrene. mRNA was quantified by quantitative polymerase chain reaction after 24 h of culture. Pro- (IL-1beta, IL 6, and TNF-alpha) and anti-inflammatory (IL-4, IL-10) protein levels were measured by ELISA after 1 or 3 days of culture. RESULTS: Quantitatively, microroughness was similar on all surfaces. Qualitatively, nanostructures were present on modSLA surfaces that were denser on Ti than on TiZr. modSLA surfaces were determined hydrophilic (high-energy surface) while SLA surfaces were hydrophobic (low-energy surface). Cells on high-energy surfaces had higher levels of mRNA from anti-inflammatory markers characteristic of M2 activation compared to cells on low-energy surfaces. This effect was enhanced on the TiZr surfaces when compared to cells on Ti SLA and Ti modSLA. Macrophages cultured on TiZr SLA and modSLA surfaces released more anti-inflammatory cytokines. CONCLUSIONS: The combination of high-energy and altered surface chemistry present on TiZr modSLA was able to influence macrophages to produce the greatest anti-inflammatory microenvironment and reduce extended pro-inflammatory factor release. PMID- 27006245 TI - [Hepatitis C infection: Therapeutic strategies]. AB - The development of new direct acting antivirals has significantly modified strategies to treat chronic hepatitis C. Treatments were previously made of an interferon-based combination. This article aims to review the direct acting antivirals clinical data and to discuss the new regimens for the management of chronic hepatitis C. Direct acting antivirals combinations - with or without ribavirin - are the new chronic hepatitis C standard treatment regimen. These combinations often result in sustained viral response rate (>90%, including in patients with uncomplicated cirrhosis) after a 12-week treatment for most patients. The innovation could represent a new era for patients with unmet medical need (especially ineligible or non-responders to interferon and/or ribavirin patients). Further investigations are required to confirm the efficacy in specific population (complicated cirrhosis, pre- or post-transplantation, chronic renal failure, comorbidities, etc.) where clinical data are still limited. Other treatments are currently being developed and might lead to new perspectives, especially in terms of treatment duration or therapeutic simplification. PMID- 27006246 TI - [A glioblastoma reveals tuberous sclerosis complex]. PMID- 27006247 TI - The potential role of irisin in the thermoregulatory responses to mild cold exposure in adults. AB - OBJECTIVES: To determine the acute effect of a mild cold exposure on thermoregulatory thermogenesis and the role of circulating irisin in the process. METHODS: We studied 22 adults (9 males, 13 females) aged 57.7 +/- 10.07 years and body mass index 27.8 +/- 4.52 kg/m(2) . Participants experienced a 90-min exposure to 20 degrees C and 25 degrees C in a randomized cross-over design. Resting metabolic rate (RMR), forearm to finger-tip gradient (FFG), blood pressure (BP), in-the-ear temperature (IET), and fasting bloods were measured on each occasion. RESULTS: There were significant increases in FFG [mean +/- SD: +3.8 +/- 3.0 degrees C, P < 0.001], systolic blood pressure (SBP) [+8 +/- 13 mm Hg, P = 0.015], and diastolic blood pressure (DBP) [+4 +/- 6 mm Hg, P = 0.005] and decreases in IET [-0.24 +/- 0.29 degrees C, P = 0.001]. Overall, RMR [+190 +/ 570 kJ/d, P = 0.135], irisin, glucose or insulin did not differ between temperatures. There were no significant between-gender differences, but males significantly increased SBP (+12 +/- 16, P = 0.02) and DBP (+6 +/- 7, P = 0.02) with decreases in heart rate (-4 +/- 3, P = 0.002), while females did not. Moreover men had approximately 50% higher thermogenic response while women had approximately 25% greater vasoconstrictor response. Adjusted for age, gender, insulin sensitivity, and body composition, fold changes in irisin were inversely related to respiratory quotient (r= -0.54, P = 0.048), while IET was related to FFG (r= -0.55, P = 0.043). CONCLUSIONS: Mild cold exposure increased vasoconstriction with a drop in IET and these were related. Greater irisin was related to a greater fasting fat oxidation in the absence of shivering. A potential gender bias in thermoregulation was noted. Am. J. Hum. Biol. 28:699 704, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27006249 TI - Pancreatic cancer: Sensory neuron ablation ameliorates PDAC. PMID- 27006248 TI - Relationship between lung function and quantitative computed tomographic parameters of airway remodeling, air trapping, and emphysema in patients with asthma and chronic obstructive pulmonary disease: A single-center study. AB - BACKGROUND: There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters. OBJECTIVES: We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation. METHODS: Asthmatic patients (n = 171), patients with COPD (n = 81), and healthy subjects (n = 49) recruited from a single center underwent QCT and clinical characterization. RESULTS: Proximal airway percentage wall area (%WA) was significantly increased in asthmatic patients (62.5% [SD, 2.2]) and patients with COPD (62.7% [SD, 2.3]) compared with that in healthy control subjects (60.3% [SD, 2.2], P < .001). Air trapping measured based on mean lung density expiratory/inspiratory ratio was significantly increased in patients with COPD (mean, 0.922 [SD, 0.037]) and asthmatic patients (mean, 0.852 [SD, 0.061]) compared with that in healthy subjects (mean, 0.816 [SD, 0.066], P < .001). Emphysema assessed based on lung density measured by using Hounsfield units below which 15% of the voxels lie (Perc15) was a feature of COPD only (patients with COPD: mean, -964 [SD, 19.62] vs asthmatic patients: mean, -937 [SD, 22.7] and healthy subjects: mean, -937 [SD, 17.1], P < .001). Multiple regression analyses showed that the strongest predictor of lung function impairment in asthmatic patients was %WA, whereas in the COPD and asthma subgrouped with postbronchodilator FEV1 percent predicted value of less than 80%, it was air trapping. Factor analysis of QCT parameters in asthmatic patients and patients with COPD combined determined 3 components, with %WA, air trapping, and Perc15 values being the highest loading factors. Cluster analysis identified 3 clusters with mild, moderate, or severe lung function impairment with corresponding decreased lung density (Perc15 values) and increased air trapping. CONCLUSIONS: In asthmatic patients and patients with COPD, lung function impairment is strongly associated with air trapping, with a contribution from proximal airway narrowing in asthmatic patients. PMID- 27006250 TI - NAFLD: Loss of CD4(+) T cells in HCC. PMID- 27006251 TI - Paediatrics: Gut microbiota dysbiosis precedes NEC. PMID- 27006252 TI - Crohn's disease: Impaired bacterial clearance in IBD. PMID- 27006253 TI - Stem cells: High-fat diet influences intestinal stem cell biology. PMID- 27006254 TI - Viral hepatitis: HCV compartmentalization in HCC: driver, passenger or both? PMID- 27006255 TI - Therapy: Risks associated with chronic PPI use - signal or noise? PMID- 27006256 TI - Colorectal cancer: Overcoming resistance to anti-EGFR therapy - where do we stand? PMID- 27006257 TI - Prospects for ending the HIV epidemic among persons who inject drugs in Haiphong, Vietnam. AB - BACKGROUND: To examine the prospects for "ending the HIV epidemic" among persons who inject drugs (PWID) in Haiphong, Vietnam. Reaching an incidence of <0.5/100 person-years at risk (PY) was used as an operational definition for "ending the epidemic." METHODS: A respondent driven sampling study of 603 PWID was conducted from September to October 2014. Current heroin use (verified with urine testing and marks of injection) was an eligibility requirement. A structured questionnaire was administered by trained interviewers to obtain demographic, drug use, and risk behavior data; HIV counseling and testing and HCV testing was also conducted. Two methods (by assuming all new injectors were HIV negative at first injection and by slope of prevalence by years injecting) were used for estimating HIV among persons injecting for <5 years ("new injectors"). Comparisons were made to the HIV epidemic among PWID in New York City and modeling of the HIV epidemic in Can Tho province. RESULTS: HIV prevalence was 25% in 2014, down from 68% in 2006 and 48% in 2009; overall HCV prevalence in the study was 67%. Among HIV seropositive PWID, 33% reported receiving antiretroviral treatment. The great majority (83%) of subjects reported pharmacies as their primary source of needles and syringes and self-reported receptive and distributive syringe sharing were quite low (<6%). Estimating HIV incidence among non-MSM male new injectors with the assumption that all were HIV negative at first injection gave a rate of 1.2/100 person-years (95% CI -0.24, 3.4). Estimating HIV incidence by the slope of prevalence by years injecting gave a rate of 0.8/100 person-years at risk (95% CI -0.9, 2.5). CONCLUSIONS: The current HIV epidemic among PWID in Haiphong is in a declining phase, but estimated incidence among non-MSM new injectors is approximately 1/100 person-years and there is a substantial gap in provision of ART for HIV seropositives. Scaling up interventions, particularly HIV counseling and testing and antiretroviral treatment for all seropositive PWID, should accelerate the decline. Ending the epidemic is an attainable public health goal. PMID- 27006258 TI - Regulation of loquat fruit low temperature response and lignification involves interaction of heat shock factors and genes associated with lignin biosynthesis. AB - Transcriptional regulatory mechanisms underlying lignin metabolism have been widely studied in model plants and woody trees, as well as fruit, such as loquat (Eriobotrya japonica). Unlike the well-known NAC, MYB and AP2/ERF transcription factors, the roles of heat shock factors (HSFs) in lignin regulation have been rarely reported. Two treatments (heat treatment, HT; low temperature conditioning, LTC) were applied to alleviate low temperature-induced lignification in loquat fruit. Gene expression analysis indicated that EjHSF1 transcript abundance, in parallel with heat shock protein genes (EjHsp), was induced by HT, while expression of EjHSF3 was repressed by LTC. Using dual luciferase assays, EjHSF1 and EjHSF3 trans-activated the promoters of EjHsp genes and lignin biosynthesis-related genes, respectively. Thus, two distinct regulatory mechanisms of EjHSF transcription factors in chilling injury-induced fruit lignification are proposed: EjHSF1 transcriptionally regulated EjHsp genes are involved in chilling tolerance, while EjHSF3 transcriptionally regulated lignin biosynthesis. Furthermore, the relations between EjHSF3 and previously characterized fruit lignification regulators, including EjAP2-1, EjMYB1 and EjMYB2, were also investigated. Yeast-two hybrid (Y2H) and biomolecular fluorescence complementation (BiFC) assays demonstrated protein-protein interaction between EjHSF3 and EjAP2-1. Thus, the involvement of EjHSF3 in fruit lignification is via both lignin biosynthetic genes and the regulator, EjAP2-1. PMID- 27006259 TI - Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia. AB - Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization, and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches. PMID- 27006260 TI - Surface functionalization of nanobiomaterials for application in stem cell culture, tissue engineering, and regenerative medicine. AB - Stem cell-based approaches offer great application potential in tissue engineering and regenerative medicine owing to their ability of sensing the microenvironment and respond accordingly (dynamic behavior). Recently, the combination of nanobiomaterials with stem cells has paved a great way for further exploration. Nanobiomaterials with engineered surfaces could mimic the native microenvironment to which the seeded stem cells could adhere and migrate. Surface functionalized nanobiomaterial-based scaffolds could then be used to regulate or control the cellular functions to culture stem cells and regenerate damaged tissues or organs. Therefore, controlling the interactions between nanobiomaterials and stem cells is a critical factor. However, surface functionalization or modification techniques has provided an alternative approach for tailoring the nanobiomaterials surface in accordance to the physiological surrounding of a living cells; thereby, enhancing the structural and functional properties of the engineered tissues and organs. Currently, there are a variety of methods and technologies available to modify the surface of biomaterials according to the specific cell or tissue properties to be regenerated. This review highlights the trends in surface modification techniques for nanobiomaterials and the biological relevance in stem cell-based tissue engineering and regenerative medicine. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:554-567, 2016. PMID- 27006261 TI - Preferential tumor cellular uptake and retention of indocyanine green for in vivo tumor imaging. AB - Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions. PMID- 27006262 TI - Clustering and diagnostic modelling of slimming aids based on chromatographic and mass spectrometric fingerprints. AB - Herbal medicines and food supplements intended as slimming aids are increasingly gaining popularity worldwide, especially for treating obesity. In this study, an ultra-performance liquid chromatography coupled to photodiode array detection (UPLC-PDA) and an ultra-performance liquid chromatography mass spectrometry (UPLC MS) method were developed to analyze 92 slimming aids (confiscated by customs), aimed at acquiring highly informative fingerprints. Three types of fingerprints were acquired (PDA, Total Ion Chromatograms (TIC), and MS fingerprints) which were used in the chemometric data analysis. Both unsupervised (i.e., Hierarchical Cluster Analysis (HCA)) and supervised techniques (i.e., Classification and Regression Tree (CART) and Partial Least Squares - Discriminant Analysis (PLS DA)) were applied. The aim was to perform an in-depth study of the samples, thereby exploring potential patterns present in the data. HCA was able to generate a clustering which was mainly defined by chemical compounds detected in the samples, i.e., sibutramine, phenolphthalein and amfepramone. PLS-DA generated the best diagnostic models for both PDA and TIC fingerprints, characterized by correct classification rates of external validation of 85% and 80%, respectively. For the MS fingerprints, the best model was obtained by CART (65% correct classification rate of external validation). Despite a lower correct classification rate, exploration of the concerned misclassifications revealed that the MS fingerprints proved to be superior since even very low concentrations of sibutramine could be detected. This study shows that reliable chemometric models can be obtained, based on the presence of prohibited chemical substances, which allow high-throughput data analysis of such samples. Moreover, they generate a prime notion of potential threat to a patient's health posed by these kinds of slimming aids. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27006263 TI - Pregnancy prediction by free sperm DNA and sperm DNA fragmentation in semen specimens of IVF/ICSI-ET patients. AB - The purpose of this study was to evaluate the predictive value of free sperm plasma DNA (f-spDNA) and sperm DNA fragmentation (SDF), in semen specimens from men undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatments. Fifty-five semen samples were evaluated during 55 consecutive IVF/ICSI-ET cycles. F-spDNA was determined by conventional quantitative real-time PCR-Sybr green detection approach, while evaluation of sperm DNA damage was performed using the sperm chromatin dispersion (SCD) assay. While f-spDNA only correlated with total sperm count, SDF correlated with many semen parameters (including sperm concentration, total sperm count and the per cent of non-progressive sperm). Neither SDF nor the proportion of sperm with small or no halos correlated with f-spDNA. Interestingly, smoking status correlated with f-spDNA but not with SDF. Although these two factors seem to interact for the prediction of pregnancy, receiver-operating characteristics (ROC) analysis revealed that SDF had a stronger predictive value (AUC = 0.7, p < 0.05) than f-spDNA (AUC = 0.6, p > 0.05). SDF and f-spDNA may not be associated together but they interact at a significant level in order to exert their actions on pregnancy outcome. Among the two markers, SDF appears to have stronger and significantly predictive value for pregnancy success. PMID- 27006264 TI - Change, organizations, and good scouts. PMID- 27006265 TI - Osteomalacia by a mesenchymal-FGF23-producing tumour: Successful treatment with radiofrequency ablation. A case report. PMID- 27006266 TI - A randomized controlled trial of 2 protocols for weaning cardiac surgical patients receiving adaptive support ventilation. AB - PURPOSE: This study aims to compare the effectiveness of weaning with adaptive support ventilation (ASV) incorporating progressively reduced or constant target minute ventilation in the protocol in postoperative care after cardiac surgery. MATERIAL AND METHODS: A randomized controlled unblinded study of 52 patients after elective coronary artery bypass surgery was carried out to determine whether a protocol incorporating a decremental target minute ventilation (DTMV) results in more rapid weaning of patients ventilated in ASV mode compared to a protocol incorporating a constant target minute ventilation. RESULTS: Median duration of mechanical ventilation (145 vs 309 minutes; P = .001) and intubation (225 vs 423 minutes; P = .005) were significantly shorter in the DTMV group. There was no difference in adverse effects (42% vs 46%) or mortality (0% vs 0%) between the 2 groups. CONCLUSIONS: Use of a DTMV protocol for postoperative ventilation of cardiac surgical patients in ASV mode results in a shorter duration of ventilation and intubation without evidence of increased risk of adverse effects. PMID- 27006267 TI - Ultrasound images transmitted via FaceTime are non-inferior to images on the ultrasound machine. AB - PURPOSE: Remote telementored ultrasound (RTMUS) systems can deliver ultrasound (US) expertise to regions lacking highly trained bedside ultrasonographers and US interpreters. To date, no studies have evaluated the quality and clinical utility of US images transmitted using commercially available RTMUS systems. METHODS: This prospective pilot evaluated the quality of US images (right internal jugular vein, lung apices and bases, cardiac subxiphoid view, bladder) obtained using a commercially available iPad operating FaceTime software. A bedside non-physician obtained images and a tele-intensivist interpreted them. All US screen images were simultaneously saved on the US machine and captured via a FaceTime screen shot. The tele-intensivist and an independent US expert rated image quality and utility in guiding clinical decisions. RESULTS: The tele-intensivist rated FaceTime images as high quality (90% [69/77]) and could comfortably make clinical decisions using these images (96% [74/77]). Image quality did not differ between FaceTime and US images (97% (75/77). Strong inter-rater reliability existed between tele-intensivist and US expert evaluations (Spearman's rho 0.43; P<.001). CONCLUSION: An RTMUS system using commercially available two-way audiovisual technology can transmit US images without quality degradation. For most anatomic sites assessed, US images acquired using FaceTime are not inferior to those obtained directly with the US machine. PMID- 27006268 TI - Julius von Haast Fellowship Award: N. Metzler-Nolte / Chica and Heinz Schaller Research Award: E. A. Lemke / NRW Innovation Prize: R. Schlogl / Gold Medal, Universita degli Studi di Firenze: J. M. Thomas. PMID- 27006269 TI - Shear Wave Elastography in the Living, Perfused, Post-Delivery Placenta. AB - The placenta is the critical interface between the mother and the developing fetus and is essential for survival and growth. Despite the widespread use of ultrasound imaging and Doppler in obstetrics and gynecology and the recent growth of elastographic technologies, little is known about the biomechanical (elastic shear wave) properties of the placenta and the range of normal and pathologic parameters that are present. This study uses a well-developed protocol for perfusing whole placentas, post-delivery, to maintain tissue integrity and function for hours. In this model, the placenta is living, whole and maintained within normal physiologic parameters such as flow, arterial pressure and oxygen, throughout examination by ultrasound, Doppler and shear wave elastography. The preliminary results indicate that normal placental tissue on the fetal side has shear wave speeds on the order of 2 m/s, in a range similar to those of animal livers. Some abnormalities are found outside this range, and thus, elastographic measures of the placenta may provide useful assessments related to the state of the tissue. PMID- 27006270 TI - Improving drug prescription in elderly diabetic patients. PMID- 27006271 TI - The challenge of predicting problematic chemicals using a decision analysis tool: Triclosan as a case study. AB - Manufacturers lack a reliable means for determining whether a chemical will be targeted for deselection from their supply chain. In this analysis, 3 methods for determining whether a specific chemical (triclosan) would meet the criteria necessary for being targeted for deselection are presented. The methods included a list-based approach, use of a commercially available chemical assessment software tool run in 2 modes, and a public interest evaluation. Our results indicated that triclosan was included on only 6 of the lists reviewed, none of which were particularly influential in chemical selection decisions. The results from the chemical assessment tool evaluations indicated that human and ecological toxicity for triclosan is low and received scores indicating that the chemical would be considered of low concern. However, triclosan's peak public interest tracked several years in advance of increased regulatory scrutiny of this chemical suggesting that public pressure may have been influential in deselection decisions. Key data gaps and toxicity endpoints not yet regulated such as endocrine disruption potential or phototoxicity, but that are important to estimate the trajectory for deselection of a chemical, are discussed. Integr Environ Assess Manag 2017;13:198-207. (c) 2016 SETAC. PMID- 27006272 TI - Incidence of high dosage buprenorphine and methadone shopping behavior in a retrospective cohort of opioid-maintained patients in France. AB - BACKGROUND: Opioid Substitution Treatment (OST) misuse and diversion have significantly increased worldwide. Obtaining OST prescriptions from multiple prescribers, known as doctor shopping, is a way in which opioids may be diverted. OBJECTIVES: The aim of this study was to assess the incidence of OST (high dosage buprenorphine (HDB) and methadone (MTD)) shopping behavior and identify associated risk factors, and its impact on mortality. METHODS: A retrospective cohort of patients treated by OST between April 1, 2004 and December 31, 2012 from a sample of the French Health Insurance database was established. Doctor shopping was defined as >=1 day of overlapping prescriptions written by >=2 different prescribers and filled in >=3 different pharmacies. RESULTS: A total of 2043 patients were enrolled, 1450HDB and 593 MTD. The one-year incidence of shopping behavior was 8.4% (95% CI: 7.0-10.1) in HDB group and 0% in MTD group, compared to 0.2% (95% CI: 0.1-0.2) for diuretics. On multivariate analysis, factors associated with HDB shopping behavior were: male gender HR: 1.74 (95% CI: 1.20-2.54); low-income status HR: 2.95 (95% CI: 2.07-4.44); mental health disorders HR: 1.43 (95% CI: 1.06-1.94); concurrent hypnotics use HR: 1.90 (95% CI: 1.39-2.61); concurrent use of weak opioids HR: 1.48 (95% CI: 1.09-1.99) and morphine HR: 1.69 (95% CI: 1.02-2.80). HDB shoppers had a higher, yet non significant risk of death (HR: 1.56 (95% CI: 0.64-3.81)) than non HDB shoppers. CONCLUSION: Shopping behavior was only found in high dosage buprenorphine patients and concerned almost one out ten patients. PMID- 27006273 TI - Cost-effectiveness of multidimensional family therapy compared to cognitive behavioral therapy for adolescents with a cannabis use disorder: Data from a randomized controlled trial. AB - OBJECTIVE: To evaluate the cost-effectiveness of Multidimensional Family Therapy (MDFT) for adolescents with a cannabis use disorder, compared to Cognitive Behavioural Therapy (CBT). METHODS: A parallel-group randomized controlled trial was performed. 109 adolescents with a DSM-IV cannabis use disorder (CBT n=54; MDFT n=55) were included. Assessments were conducted at baseline, and 3, 6, 9 and 12 months post-baseline, and included measures on cannabis and other substance use, delinquency, health care utilization, and general health related quality of life. RESULTS: Excluding those with missing cost-data, 96 participants (MDFT n=49; CBT n=47) were included. From a health care perspective, the average annual direct medical costs in the CBT group were ?2015 (95%C.I. 1397-2714), compared to ?5446 (95%C.I. 4159-7092) in the MDFT group. The average quality-adjusted life years (QALY's) gained were 0.06 QALY higher for the MDFT group, which led to an incremental cost-effectiveness ratio (ICER) of 54,308 Euro/QALY or ?43,405 per recovered patient. Taking the costs of delinquency into account, the costs increased to ?21,330 (95%C.I. 12,389-32,894) for the CBT group and to ?21,915 (95%C.I. 16,273-28,181) for the MDFT group, which lead to an ICER of 9266 Euro/QALY or a cost per recovered patient of ?7491. CONCLUSIONS: This is the first comprehensive CEA of MDFT compared to CBT and it demonstrated that when costs of delinquency were included, the ICERS were modest. The results underline the importance of adopting a broader perspective regarding cost effectiveness analyses in mental health care. PMID- 27006275 TI - Eyes without a ribbon. PMID- 27006276 TI - It's a family act: the geminin triplets take center stage in motile ciliogenesis. PMID- 27006277 TI - Elucidating the DDK-dependent step in replication initiation. PMID- 27006278 TI - Influenza infections and risk of Alzheimer's disease. AB - Influenza may cause neuropsychiatric disorders, including confusion, delirium, convulsions, and encephalopathy. We conducted a case-control study to evaluate the association between diagnosed influenza and the risk of developing Alzheimer's disease (AD) using the UK-based Clinical Practice Research Datalink (CPRD). We identified 19,463 patients who developed an incident AD diagnosis between 1998 and 2013 and matched them 1:1 to dementia-free controls on age, sex, general practice, calendar time and number of years of recorded history. We calculated adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of developing AD in association with previous influenza infections and stratified by number of infections prior to the AD diagnosis date. Patients with a previous influenza infection were not at an increased risk of developing AD as compared to those with no previous infection (aOR, 95% CI 0.94, 0.87-1.02) overall. Nor was increasing number of infections related to an increased risk of developing AD; the aOR (95% CI) for those with 1, 2, or ?3 episodes was 0.98 (0.90-1.07), 0.70 (0.56-0.88), and 0.92 (0.63-1.34), respectively. Presence of an underlying chronic inflammatory disease in those with an influenza infection did not increase the risk of developing AD (aOR, 95% CI 0.83, 0.71-0.96), either, and there was no association between the severity of influenza infections (based on recorded neurological or bacterial complications) and the risk of AD. In conclusion, considering the limitations of this large observational study, we found no association between influenza infections and the risk of developing AD. PMID- 27006279 TI - MiR-30a inhibits Th17 differentiation and demyelination of EAE mice by targeting the IL-21R. AB - T helper cells 17 (Th17) are recognized as key participants in the pathogenesis of chronic autoimmune diseases such as multiple sclerosis (MS). Regulation of Th17 differentiation is a valuable strategy for diagnosis and treatment of these complicated immune disorders. Here, by genome-wide expression profiling of microRNAs (miRs), we screened miR-30a, whose level was greatly decreased during Th17 differentiation and the process of demyelination disease, both in MS patients and experimental autoimmune encephalomyelitis (EAE) mice. Enforced constitutive expression of miR-30a in naive T cells inhibited their differentiation into Th17, and in vivo overexpression of miR-30a resulted in fewer Th17 and alleviative EAE. Moreover, target prediction analysis and dual luciferase report assay revealed that interleukin-21 receptor (IL-21R) was a direct target of miR-30a, a finding consistent with the results that miR-30a downregulated the expression of IL-21R, while overexpression of IL-21R alleviated the inhibitory effect of miR-30a on Th17 differentiation. Taken together, our findings imply that miR-30a inhibits Th17 differentiation and the pathogenesis of MS by targeting IL-21R. PMID- 27006280 TI - Compromised in vitro dissolution and membrane transport of multidrug amorphous formulations. AB - Herein, the thermodynamic properties of solutions evolving from the non-sink dissolution of amorphous solid dispersions (ASDs) containing two or more drugs have been evaluated, focusing on the maximum achievable supersaturation and tendency of the system to undergo liquid-liquid phase separation (LLPS). Ritonavir (RTV) and atazanavir (ATV) were co-formulated with polyvinylpyrrolidone to produce ASDs with different molar ratios of each drug, and the dissolution profile of each drug was studied under non-sink conditions. The phase behavior of the supersaturated solutions generated by ASD dissolution was compared to that of supersaturated solutions generated by antisolvent addition. Dissolution of an ASD containing RTV, ATV and lopinavir (LPV) was also investigated. A thermodynamic model was used to predict the maximum achievable supersaturation for ASDs containing two and three drugs. In addition, a transport study with Caco-2 cells was conducted to evaluate the impact of co-addition of drugs on membrane transport. It was found that the formulation containing a 1:1 molar ratio of RTV and ATV achieved only 50% of the supersaturation attained by dissolution of the single drug systems. The maximum achievable concentration of ATV decreased linearly as the mole fraction of ATV in the formulation decreased and a similar trend was observed for RTV. For the dispersion containing a 1:1:1 molar ratio of RTV, ATV and LPV, the maximum concentration of each drug was only one third of that achieved for the single drug formulations. The decrease in the achievable supersaturation was well-predicted by the thermodynamic model for both the binary and ternary drug combinations. These observations can be explained by a decrease in the concentration at which the drugs undergo LLPS in the presence of other miscible drugs, thereby reducing the maximum achievable supersaturation of each drug. The reduced free drug concentration was reflected by a decreased flux across Caco-2 cells for the drug combinations compared to drug alone. This study sheds light on the complex dissolution and solution phase behavior of multicomponent amorphous dosage forms, in particular those containing poorly water soluble drugs, which may undergo supersaturation in vivo. PMID- 27006281 TI - Higher detection rates of amino acid substitutions in HBV reverse transcriptase/surface protein overlapping sequence is correlated with lower serum HBV DNA and HBsAg levels in HBeAg-positive chronic hepatitis B patients with subgenotype B2. AB - OBJECTIVES: Hepatitis B virus (HBV) subgenotype B2 is prevalent in China and some other parts of Asia. This study aimed to carry out a subgenotype B2 specific mutation analysis on important amino acid (AA) sites in overlapping reverse transcriptase (RT) and surface (S) protein coding regions of HBV. MATERIALS AND METHODS: A total of 143 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with HBV subgenotype B2 infection were enrolled. HBV RT/S regions were sequenced focusing on 43 RT resistance AA sites and 31 S AA sites with functional/structural/conformational importance. RESULTS: According to the consensus AA sequence for subgenotype B2, 49.7% (71/143) of RT and 33.6% (48/143) of S protein sequences contained detectable substitutions at 58.1% (25/43) of studied AA sites in RT and 51.6% (16/31) of AA sites in S proteins, respectively. The most frequently detected substitutions were rtN134D/S (44/143, 30.8%) and sT126A/S (22/143, 15.4%), which were located in the RT A-B interdomain region and the corresponding antigenicity determinant region of S protein, respectively. In addition, two patients harboring drug resistance mutations rtL80V+rtM204I and rtL180M+rtM204V were found. Interestingly, the patients with detectable AA substitutions at any of the 74 sites in either/both of RT/S sequences had significantly lower serum HBV DNA and HBsAg levels than that in patients without detectable RT/S AA substitutions (P<0.05). A trend Chi-squared test indicated that a negative association of serum HBsAg level with S protein sequence substitution rate was statistically significant (P=0.047). CONCLUSION: This subgenotype B2 specific mutation analysis revealed some naturally occurring hot spot substitutions at important AA sites of HBV RT/S proteins, which together might influence the serum HBV DNA and HBsAg levels in HBeAg-positive CHB patients. PMID- 27006282 TI - CB2 cannabinoid receptor is involved in the anti-inflammatory effects of leptin in a model of traumatic brain injury. AB - BACKGROUND AND PURPOSE: The rates for traumatic brain injury (TBI) have risen in the last decade. Studies in animal models and clinical trials have not yet resulted in an effective treatment for TBI. Leptin, a 16kDa peptidic hormone is mainly known as a regulator of energy balance and has been shown to exert neuroprotective effects in different models of brain pathology. In this study, we have assessed whether leptin exerts protective actions in a TBI mouse model. In addition, the possible implication of CB2 cannabinoid receptor in leptin actions has been explored, since it is known that the endocannabinoid system interacts with leptin and actively participates in brain recovery after lesions. METHODS: Swiss (CD1) male mice were subjected to weigh-drop model for TBI. Prior to the lesion, mice were injected with an antagonist of CB2 receptor (AM630) or the vehicle and immediately after TBI, they received leptin or vehicle treatment. Data were analyzed using a two-way ANOVA or the non-parametric test Kruskal Wallis when appropriate. For correlation analyses, Spearman's rho test, followed by linear regression test, was used. RESULTS: TBI induced a neurological deficit, which was improved by leptin treatment. Leptin recovered several parameters affected by TBI, including the expression of cannabinoid receptors, axonal injury marker and neuroinflammatory components. The effects of leptin were prevented or reduced when it was administered in combination with the CB2 receptor antagonist, AM630. CONCLUSIONS AND IMPLICATIONS: Since some of the beneficial effects of leptin were not evident in the presence of AM630, our results suggest that CB2 receptor might be involved in the full expression of the neuroprotective effects of the hormone. These findings open new avenues for the study of leptin as a therapeutic treatment for TBI and enhance the importance of CB2 receptor in TBI pathophysiology and recovery. PMID- 27006283 TI - Xenobiotic Pathway Gene Polymorphisms Associated with Gastric Cancer in High Risk Mizo-Mongoloid Population, Northeast India. AB - BACKGROUND: The aim of this study was to evaluate the risk of gastric cancer associated with individual or combined glutathione S-transferases (GSTs) polymorphism and their interaction with environmental factors. MATERIALS AND METHODS: Genotyping by PCR was carried out for 80 cases and controls each for GSTM1, GSTT1, and GSTP1 polymorphism and mapped for gene-environment association studies. The samples were subjected to pathogen detection and GSTP1 expression for analyzing their association with different genotypes. Logistic regression analyses were conducted to compute the influence of both genetic and environmental factors for gastric cancer. MDR analysis was performed to assess the risk of gastric cancer by studying the gene-gene and gene-environment effect on the basis of GST genotyping and GSTP1 gene expression. RESULTS: Infection with Helicobacter pylori and CagA+ strains was more frequent in patients with GSTM1/T1 null genotype. Intake of high fermented fat and smoked meat was found to be significantly associated with gastric cancer. The G/G, A/G (rs1695), and T/T (rs1138272) were found to be significantly associated with low expression of GSTP1 gene in cancer tissue. CONCLUSION: Presence of H. pylori with CagA genotype showed significant individual effect with GSTT1 polymorphism as well as strong synergistic effect in gastric cancer risk. Majority of the gastric cancer samples showed significant negative expression in G/G, A/G (rs1695), and T/T (rs1138272) genotypes. This study shows that GST gene polymorphism was significantly relevant for determining the individual susceptibility to gastric cancer. PMID- 27006285 TI - Loss of orofacial tissue secondary to septic shock caused by Streptococcus pneumoniae. AB - Purpura fulminans is a rare complication of septic shock with a high mortality. It can result in a severe loss of skin, and often amputation of limbs. Managing the loss of tissue is a challenge that requires a multidisciplinary approach. PMID- 27006284 TI - Ca(2+) monitoring in Plasmodium falciparum using the yellow cameleon-Nano biosensor. AB - Calcium (Ca(2+))-mediated signaling is a conserved mechanism in eukaryotes, including the human malaria parasite, Plasmodium falciparum. Due to its small size (<10 MUm) measurement of intracellular Ca(2+) in Plasmodium is technically challenging, and thus Ca(2+) regulation in this human pathogen is not well understood. Here we analyze Ca(2+) homeostasis via a new approach using transgenic P. falciparum expressing the Ca(2+) sensor yellow cameleon (YC)-Nano. We found that cytosolic Ca(2+) concentration is maintained at low levels only during the intraerythrocytic trophozoite stage (30 nM), and is increased in the other blood stages (>300 nM). We determined that the mammalian SERCA inhibitor thapsigargin and antimalarial dihydroartemisinin did not perturb SERCA activity. The change of the cytosolic Ca(2+) level in P. falciparum was additionally detectable by flow cytometry. Thus, we propose that the developed YC-Nano-based system is useful to study Ca(2+) signaling in P. falciparum and is applicable for drug screening. PMID- 27006286 TI - Effect of a low dose of midazolam on high blood pressure in dental patients: a randomised, double-blind, placebo-controlled, two-centre study. AB - Some patients have transient hypertension before dental treatment as a result of anxiety and stress. Midazolam is an anxiolytic, and thought to be effective for the management of this sort of transient hypertension. We have evaluated in a randomised, controlled trial whether a low dose of midazolam can lower blood pressure in dental patients to an acceptable level without excessive sedation. Suitable patients were randomised to be given midazolam (trial group) or physiological saline (control group) intravenously. Blood pressure, heart rate, degree of anxiety, and amount of sedation were measured before and after injection. After injection, blood pressure in the trial group significantly decreased to clinically acceptable levels compared with controls. The degree of anxiety in the trial group was also significantly less than that in the control group, but there were no significant differences in sedation. These results suggest that injection of a low dose of midazolam stabilises the blood pressure of dental patients with transient hypertension. PMID- 27006287 TI - Use of a dermal regeneration template and full-thickness skin grafts to reconstruct exposed bone in the head and neck. AB - Soft tissue defects over bone are difficult to reconstruct and this is compounded when there is no periosteum. We present what is to our knowledge the first reported use of a dermal regeneration template (Integra(r), Integra Life Sciences Corp, Plainsboro, NJ, USA) to assist in reconstruction over an exposed mandible. PMID- 27006288 TI - Geographically Sourcing Cocaine's Origin - Delineation of the Nineteen Major Coca Growing Regions in South America. AB - Previously, geo-sourcing to five major coca growing regions within South America was accomplished. However, the expansion of coca cultivation throughout South America made sub-regional origin determinations increasingly difficult. The former methodology was recently enhanced with additional stable isotope analyses ((2)H and (18)O) to fully characterize cocaine due to the varying environmental conditions in which the coca was grown. An improved data analysis method was implemented with the combination of machine learning and multivariate statistical analysis methods to provide further partitioning between growing regions. Here, we show how the combination of trace cocaine alkaloids, stable isotopes, and multivariate statistical analyses can be used to classify illicit cocaine as originating from one of 19 growing regions within South America. The data obtained through this approach can be used to describe current coca cultivation and production trends, highlight trafficking routes, as well as identify new coca growing regions. PMID- 27006289 TI - Assessing torsion of the medial cortex of the canine tibia using computed tomography multiplanar reconstruction. AB - OBJECTIVES: To describe a protocol for the measurement of tibial rotational alignment using CT multiplanar reconstructions. To establish the feasibility of producing general guidelines for the amount of torsional contouring to apply to a bone plate applied to the medial aspect of the tibia during repair of a non reducible tibial fracture. METHODS: CT scans of the pelvic limbs of 15 chondrodystrophic and 34 non-chondrodystrophic dogs were studied. Medial tibial cortex torsion angle and distal medial tibial cortex angle were determined from CT multiplanar reconstructions. Medial plate application was simulated using a plate contoured to the group mean medial tibial cortex torsion angle and post simulation tibial rotational alignment was assessed. RESULTS: Mean medial tibial cortex torsion angles were 23 degrees (chondrodystrophic) and 26 degrees (non chondrodystrophic). Following simulated plate application the change in medial tibial cortex torsion was less than 10 degrees in 73% of chondrodystrophic and 93% of non-chondrodystrophic tibias. In total, 93% of chondrodystrophic and 97% of non-chondrodystrophic tibias had post-simulation distal medial tibial cortex angle less than 10 degrees from the group mean pre-simulation distal medial tibial cortex angle. CLINICAL SIGNIFICANCE: Medial tibial cortex torsion and tibial rotational alignment can be measured using the protocol described in this study. 26 degrees of internal torsional tibial plate pre-contouring may be appropriate for non-chondrodystrophic dogs, but further clinical validation is required. PMID- 27006290 TI - Potential neurobiological benefits of exercise in chronic pain and posttraumatic stress disorder: Pilot study. AB - This pilot study assessed the effects of cardiopulmonary exercise testing and cardiorespiratory fitness on plasma neuropeptide Y (NPY), allopregnanolone and pregnanolone (ALLO), cortisol, and dehydroepiandrosterone (DHEA), and their association with pain sensitivity. Medication-free trauma-exposed participants were either healthy (n = 7) or experiencing comorbid chronic pain/posttraumatic stress disorder (PTSD) (n = 5). Peak oxygen consumption (VO2) during exercise testing was used to characterize cardiorespiratory fitness. Peak VO2 correlated with baseline and peak NPY levels (r = 0.66, p < 0.05 and r = 0.69, p < 0.05, respectively), as well as exercise-induced changes in ALLO (r = 0.89, p < 0.001) and peak ALLO levels (r = 0.71, p < 0.01). NPY levels at the peak of exercise correlated with pain threshold 30 min after exercise (r = 0.65, p < 0.05), while exercise-induced increases in ALLO correlated with pain tolerance 30 min after exercise (r = 0.64, p < 0.05). In contrast, exercise-induced changes in cortisol and DHEA levels were inversely correlated with pain tolerance after exercise (r = -0.69, p < 0.05 and r = -0.58, p < 0.05, respectively). These data suggest that cardiorespiratory fitness is associated with higher plasma NPY levels and increased ALLO responses to exercise, which in turn relate to pain sensitivity. Future work will examine whether progressive exercise training increases cardiorespiratory fitness in association with increases in NPY and ALLO and reductions in pain sensitivity in chronic pain patients with PTSD. PMID- 27006291 TI - The association of a hemivertebra with a large dumbbell-shaped tumor: A potential embryological explanation. PMID- 27006292 TI - Learning-oriented assessment increases performance and written skills in a second year metabolic biochemistry course. AB - Assessment plays a critical role in learning and teaching and its power to enhance engagement and student outcomes is still underestimated in tertiary education. The current project considers the impact of a staged redesign of an assessment strategy that emphasized relevance of learning, formative assessment, student engagement, and feedback on student performance, failure rates and overall engagement in the course. Significant improvements in final grades (p < 0.0001) and written performance (p < 0.0001) in the final examination were noted that coincided with increased lecture attendance and overall engagement in the course. This study reinforces the importance of an integrated approach to assessment that includes well developed formative tasks and a continuous summative assessment strategy. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):412-420, 2016. PMID- 27006293 TI - Methods for a Retrospective Population-based and Clinic-based Subfertility Cohort Study: the Fertility Experiences Study. AB - BACKGROUND: Most cohort-based research for subfertility has been conducted in clinic-based cohorts, which may differ from population-based cohorts. METHODS: We retrospectively recruited parallel cohorts of subfertile women: one by sampling two specialty fertility clinics in Utah, and one by population-based sampling based on marriage and birth records. The index date (of first clinic visit or subfertility status) was between 2000 and 2009, and we linked the women recruited to subsequent birth certificate records through December 2010. RESULTS: We enrolled 459 women through clinic-based sampling and 501 women through population based sampling. Clinic-based women were older, had higher annual household income and more likely to have had a most intensive treatment of intrauterine insemination (31%) or in vitro fertilisation (46%) than women from population recruitment (19% and 14% respectively). Conversely, they were less likely to have received no medical treatment (9%) compared to women from population recruitment (41%). For both types of sampling, prior to eligibility screening, non-responders were less likely to link to a live birth than responders: 51% vs. 58% for clinic based, and 69% vs. 76% for the population-based with an index date in 2004. CONCLUSIONS: Population-based sampling for subfertility cohort research identifies women who were more likely to have had less intensive treatment or no treatment. However, in both clinic-based and population-based sampling, women who have had a live birth are more likely to respond to retrospective recruitment. PMID- 27006294 TI - Scanning Electron Microscopy of the Presbylarynx. AB - OBJECTIVE: To describe the findings on the presbylarynx under scanning electron microscopy. STUDY DESIGN: Cadaver study. SETTING: Universidade Estadual Paulista (Botucatu, Sao Paulo, Brazil). SUBJECTS AND METHODS: Sixteen vocal folds were removed during necropsies and distributed into 2 age groups: control (n = 8; aged 30-50 years) and elderly (n = 8; aged 75-92 years). The right vocal fold was dissected, fixed in glutaraldehyde 2.5%, and prepared for scanning electron microscopy. The thickness of the epithelium was measured using a scandium morphometric digital program. RESULTS: In the control group, the epithelium had 5 to 7 overlapped cell layers, rare desquamation cells, and little undulation with protruding intercellular junctions. The lamina propria showed a uniform network of collagen and elastic fibers in the superficial layer. A dense network of collagen was identified in the deeper layer. In the elderly group, the epithelium was atrophic (2-3 cells), with more desquamation cells and intercellular junctions delimited by deep sulci. The epithelial thickness was lower in elderly than in controls (mean [SD], 221.64 [145.90] um vs 41.79 [21.40] um, respectively). The lamina propria had a dense and irregular distribution of collagen and elastic fibers in the superficial layer. In the deep layers, the collagen fibers formed a true fibrotic and rigid skeleton. CONCLUSION: Scanning electron microscopy identified several changes in the elderly larynx, differentiating it from the controls. These alterations are probably related to the aging process of the vocal folds. However, the exact interpretation of these findings requires additional studies, even to the molecular level, having the fibroblasts as targets. PMID- 27006295 TI - Surgical and Audiologic Outcomes in Endoscopic Stapes Surgery across 4 Institutions. AB - OBJECTIVES: To investigate intra- and postoperative outcomes of endoscopic stapes surgery. STUDY DESIGN: Case series with chart review. SETTING: Four tertiary care otologic centers. SUBJECTS AND METHODS: Sixty-five subjects 18 years and older who underwent endoscopic stapes surgeries were analyzed. Variables analyzed included surgical techniques and intraoperative findings. Outcomes measured included postoperative hearing and complications to date. RESULTS: Fifty-one patients met inclusion and exclusion criteria. The average patient age was 48.1 years (range, 26-87 years), with 60.0% female patients. Patients had a median follow-up of 5.13 months (range, 0.8-57.4 months). Of the subjects, 71.7% required scutum removal. The chorda tympani nerve was manipulated in 94.0% of subjects and transected in 12.0%. At last follow-up visit, the median air-bone gap decreased from 34.5 dB hearing level (HL) preoperatively to 9.0 dB HL postoperatively (P < .0001). Ninety percent of subjects had closure of their air bone gap <=20 dB HL. Intraoperative complications included tympanic membrane tears in 8.0% of subjects, all of which resolved at first follow-up. Postoperatively, 10.0% of subjects complained of altered taste. CONCLUSIONS: The present multicentered study of endoscopic stapes surgery demonstrates similar audiometric and postoperative outcomes previously published in the literature, with a median postoperative air-bone gap of 9.0 dB HL. Future prospective endoscopic stapes surgery studies, addressing the need for scutum removal, postoperative taste changes, and pain scores, are merited. PMID- 27006296 TI - Safety of Outpatient Thyroid and Parathyroid Surgery: A Propensity Score-Matched Study. AB - OBJECTIVE: To test our hypothesis that general and thyroid surgery-specific complications, mortality, and postdischarge utilization for patients undergoing outpatient and inpatient thyroid and parathyroid surgery would not differ when outpatient status was defined as discharge within 8 hours of surgery completion. STUDY DESIGN: Retrospective observational cohort, 2008 to 2013. SETTING: Kaiser Permanente Northern California and Kaiser Permanente Southern California. SUBJECTS AND METHODS: We used a robust set of variables and propensity score methods to match 2362 patients undergoing hemithyroidectomy, total thyroidectomy, or parathyroidectomy surgery as outpatients to 2362 patients undergoing the same procedures as inpatients. Outcomes assessed were 30-day rates of complications, emergency department visits, all-cause hospital readmissions, and mortality. RESULTS: After matching, no statistically significant differences between inpatients and outpatients were found for complication rates or postdischarge utilization. After matching, there was no statistically significant difference between inpatients and outpatients in hematoma rates, which were 0.55% in both groups. In the matched-pair groups, 2 deaths occurred among inpatients (0.09%) and none occurred among outpatients (0.00%), a difference that was not statistically significant. CONCLUSION: Discharge within 8 hours after completion of thyroid and parathyroid surgery is as safe as inpatient surgery. PMID- 27006298 TI - Audit of Turnaround Time for a Training Oral Histopathology Laboratory in Malaysia. AB - BACKGROUND: Turnaround time (TAT) is the benchmark to assess the performance of a laboratory, pathologists, and pathology services, but there are few articles on TAT of surgical pathology, particularly in relation to oral or head and neck specimens. This study investigates the TAT for oral histopathology reporting in an academic institution's training laboratory and offers recommendations to achieve better overall quality of diagnostic services. METHODS: This study examined data obtained from biopsy request forms for specimens received from the Oro-Maxillofacial Surgery Department of Hospital Tengku Ampuan Rahimah Klang in the Oral Pathology Diagnostic Laboratory of the Faculty of Dentistry, University of Malaya, over a period of 3 years between January 2012 and October 2014. RESULTS: TAT for surgical and decalcified specimens were increased significantly compared to biopsies. Additional special handling did not influence TAT, but increased specimen volume resulted in greater TAT. Slide interpretation was the most time-consuming stage during histopathology reporting. Overall, mean TAT was acceptable for most specimens, but the TAT goals were less than satisfactory. CONCLUSION: A TAT goal appropriate for this laboratory may hence be established based on this study. Collective efforts to improve the TAT for various specimens are essential for better laboratory performance in the future. PMID- 27006297 TI - Heritability and genetic correlation between the cerebral cortex and associated white matter connections. AB - The aim of this study is to investigate the genetic influence on the cerebral cortex, based on the analyses of heritability and genetic correlation between grey matter (GM) thickness, derived from structural MR images (sMRI), and associated white matter (WM) connections obtained from diffusion MRI (dMRI). We measured on sMRI the cortical thickness (CT) from a large twin imaging cohort using a surface-based approach (N = 308, average age 22.8 +/- 2.3 SD). An ACE model was employed to compute the heritability of CT. WM connections were estimated based on probabilistic tractography using fiber orientation distributions (FOD) from dMRI. We then fitted the ACE model to estimate the heritability of CT and FOD peak measures along WM fiber tracts. The WM fiber tracts where genetic influence was detected were mapped onto the cortical surface. Bivariate genetic modeling was performed to estimate the cross-trait genetic correlation between the CT and the FOD-based connectivity of the tracts associated with the cortical regions. We found some cortical regions displaying heritable and genetically correlated GM thickness and WM connectivity, forming networks under stronger genetic influence. Significant heritability and genetic correlations between the CT and WM connectivity were found in regions including the right postcentral gyrus, left posterior cingulate gyrus, right middle temporal gyri, suggesting common genetic factors influencing both GM and WM. Hum Brain Mapp 37:2331-2347, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27006299 TI - Primitive Neuroectodermal Tumor of the Stomach: A Case Report. AB - Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a highly aggressive small round cell tumor that mainly occurs in the bone or soft tissue of children or young adults but is extremely rare in the stomach. A 55-year-old man presented with melena and anemia. On endoscopy, an ulcerofungating mass was observed in the high body and total gastrectomy was performed. Histologically, the mass consisted of small round cells with scanty cytoplasm and inconspicuous nucleoli. They often formed perivascular pseudorosettes and multinucleated giant cells were frequently observed. The tumor cells strongly expressed CD99, FLI1, and chromogranin and weakly expressed synaptophysin and CD56. EWS-FLI1 fusion transcript was confirmed by reverse transcription-polymerase chain reaction. ES/PNET is frequently misdiagnosed because of its similarity with small cell carcinoma. Although gastric ES/PNET is very rare, it should be included in differential diagnoses of small round cell tumor in the stomach. PMID- 27006300 TI - Anaplastic Sarcoma of the Kidney: A Rare Unique Renal Neoplasm. AB - Anaplastic sarcoma of the kidney (ASK) is an extremely rare tumor, which usually presents as a large renal mass. Microscopically, the tumor is composed of pleomorphic mesenchymal spindle cells with marked atypia, associated with chondroid differentiation and focal round primitive mesenchymal cells. Herein, we present a case of anaplastic sarcoma of the kidney in a 3-year-old female, who presented with a large abdominal mass. To the best of our knowledge, less than 25 cases are reported in the literature. In addition, this is the first case reported from the Middle East. PMID- 27006301 TI - Activating BRAF Mutations Detected in Mixed Hurthle Cell Carcinoma and Multifocal Papillary Carcinoma of the Thyroid Gland: Report of an Unusual Case and Review of the Literature. AB - Despite the increase in the incidence of thyroid carcinomas, the occurrence of collision tumors in the thyroid remains a rare event. We present the case of a 69 year-old female who presented to the emergency department with a chief complaint of painful neck swelling. Imaging revealed a large right hemithyroid mass and a left hemithyroid nodule. Fine needle aspiration of the lesions and subsequent total thyroidectomy revealed a Hurthle cell carcinoma in the right lobe and bilateral multicentric papillary carcinoma foci, including 2 foci with a classical pattern and 1 encapsulated follicular variant in the isthmus. BRAF gene mutation analysis revealed V600E gene mutation in the classical variants of papillary carcinoma and in the Hurthle cell carcinoma. The focus of follicular variant of papillary carcinoma in the isthmus and a sample from normal thyroid tissue did not harbor BRAF mutations. This case is remarkable in being an unusual report of a follicular Hurthle cell carcinoma harboring the BRAF V600E mutation and occurring in collision with multifocal papillary carcinoma. Documentation of such cases is important as it helps better understand the pathogenesis, clinical behavior, and radiologic findings of such rare lesions and to determine the optimal treatment modalities. PMID- 27006302 TI - Naringin inhibits lipopolysaccharide-induced damage in human umbilical vein endothelial cells via attenuation of inflammation, apoptosis and MAPK pathways. AB - Endothelial cell activation, injury and dysfunction have been regarded as one of the initial key events in the pathogenesis of atherosclerosis. Lipopolysaccharide (LPS), an important mediator of inflammation, can cause endothelial cell damage and apoptosis. Naringin (Nar), one major flavanone glycoside from citrus fruits, shows various pharmacological actions, but the effect of Nar on LPS-induced damage in human umbilical vein endothelial cells (HUVECs) remains unknown. The present results showed that Nar significantly improved the survival rate of HUVECs, and decreased reactive oxygen species and intracellular Ca(2+) levels caused by LPS compared with model group. In addition, Nar obviously decreased cytochrome c release from mitochondria into cytosol. Moreover, Nar significantly down-regulated the protein or mRNA levels of IL-1, IL-6, TNF-alpha, VCAM-1, ICAM 1, NF-kappaB, AP-1, cleaved-3,-7,-9, p53, Bak and Bax, and up-regulated the expressions of Bcl-xl, Bcl-2 to suppress inflammation and apoptosis. Furthermore, Nar obviously inhibited phosphorylation levels of JNK, ERK and p38 MAPK. In conclusion, Nar exhibited potent effects against LPS-induced damage in HUVECs through the modulation of oxidative stress, inflammation, apoptosis and MAPK pathways, which should be developed as a potent candidate for the treatment of atherosclerosis in the future. PMID- 27006303 TI - New biphenyl iminium salt catalysts for highly enantioselective asymmetric epoxidation: role of additional substitution and dihedral angle. AB - New biaryl iminium salt catalysts for enantioselective alkene epoxidation containing additional substitution in the heterocyclic ring are reported. The effects upon conformation and enantioselectivity of this additional substitution, and the influence of dihedral angle in these systems, has been investigated using a synthetic approach supported by density functional theory. Enantioselectivities of up to 97% ee were observed. PMID- 27006305 TI - Structure and dynamics of optically directed self-assembly of nanoparticles. AB - Self-assembly of nanoparticles leading to the formation of colloidal clusters often serves as the representative analogue for understanding molecular assembly. Unravelling the in situ structure and dynamics of such clusters in liquid suspensions is highly challenging. Presently colloidal clusters are first isolated from their generating environment and then their structures are probed by light scattering methods. In order to measure the in situ structure and dynamics of colloidal clusters, we have generated them using the high-repetition rate femtosecond laser pulse optical tweezer. Since the constituent of our dimer, trimer or tetramer clusters are 250 nm radius two-photon resonant fluorophore coated nanospheres under the optical trap, they inherently produce Two-Photon Fluorescence, which undergo intra-nanosphere Fluorescence Energy Transfer. This unique energy transfer signature, in turn, enables us to visualize structures and orientations of these colloidal clusters during the process of their formation and subsequent dynamics in a liquid suspension. We also show that due to shape birefringence, orientation and structural control of these colloidal clusters are possible as the polarization of the trapping laser is changed from linear to circular. We thus report important progress in sampling the smallest possible aggregates of nanoparticles, dimers, trimers or tetramers, formed early in the self-assembly process. PMID- 27006304 TI - Vaccine adjuvants as potential cancer immunotherapeutics. AB - Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund's adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID- 27006306 TI - Psychological skills training to support diabetes self-management: Qualitative assessment of nurses' experiences. AB - AIM: Evidence for the efficacy of psychological skills training as a method of supporting patients' self-management is growing, but there is a shortage of mental health providers with specialist diabetes knowledge to deliver them. Primary care nurses are now increasingly expected to learn and use these techniques. This study explores nurse experience of training in six psychological skills to support patients' self-management of type 2 diabetes. METHODS: Semi structured interviews elicited themes relating to nurses' experiences of participating in a trial of a psychological intervention, the Diabetes-6 study (D 6). Nurses were employed in GP surgeries in 5 South London boroughs. Thematic framework analysis was used to compare and contrast themes across participants. Nine nurses delivering the intervention (n=11), and 7 from the control intervention (n=12, no psychological element) were interviewed. RESULTS: Three key themes were identified: (i) positive and negative impact of D6 on nurses' practice: positives included patient empowerment; negatives included patients' capacity to engage; (ii) professional boundaries including concerns about over stepping role as a nurse and (iii) concerns about degree of support from physicians at participating practices in integrating psychological and diabetes care. CONCLUSION: Primary care nurses report that psychological skills training can have a positive impact on patient care. Significant role adjustment is required, which may be aided by additional support from the practice team. Qualitative evaluation of effectiveness of psychological interventions may reveal processes that hinder or contribute to efficacy and translation. Appropriate support is necessary for primary care nurses to deliver psychological therapies with confidence. PMID- 27006307 TI - From porphyrins to pyrphyrins: adsorption study and metalation of a molecular catalyst on Au(111). AB - The molecular ligand pyrphyrin, a tetradentate bipyridine based macrocycle, represents an interesting but widely unexplored class of molecules. It resembles the well-known porphyrin, but consists of pyridyl subunits instead of pyrroles. Metal complexes based on pyrphyrin ligands have recently shown promise as water reduction catalysts in homogeneous photochemical water splitting reactions. In this study, the adsorption and metalation of pyrphyrin on a single crystalline Au(111) surface is investigated in an ultrahigh vacuum by means of scanning tunneling microscopy, low-energy electron diffraction, X-ray photoelectron spectroscopy and density functional theory. Pyrphyrin coverages of approximately one monolayer and less are obtained by sublimation of the molecules on the substrate kept at room temperature. The molecules self-assemble in two distinct phases of long-range molecular ordering depending on the surface coverage. The deposition of cobalt metal and subsequent annealing lead to the formation of Co ligated pyrphyrin molecules accompanied by a pronounced change of the molecular self-assembly. Electronic structure calculations taking the herringbone reconstruction of Au(111) into account show that the molecules are physisorbed, but preferred adsorption sites are identified where Co and the N atoms of the two terminal cyano groups are optimally coordinated to the surface Au atoms. An intermediate state of the metalation reaction is observed and the reaction steps for the Co metalation of pyrphyrin molecules on Au(111) are established in a joint experimental and computational effort. PMID- 27006308 TI - Antiplatelet activity of chrysin via inhibiting platelet alphaIIbbeta3-mediated signaling pathway. AB - SCOPE: Propolis is thought to help prevent thrombotic and related cardiovascular diseases in humans. Chrysin, a bioflavonoids compound found in high levels in propolis and in honey, has been reported to possess antiplatelet activity. However, the mechanism by which it inhibits platelet function is unclear. METHODS AND RESULTS: The effects of chrysin on agonist-activated platelet-aggregation, granule-secretion, and integrin alphaIIbbeta3 activation were examined. Its effects on the phosphorylation of Akt, GSK3beta, MAPKs, and several proteins of the glycoprotein VI (GPVI) signaling pathway were also studied on collaged activated platelets. In addition, human platelet spreading on immobilized fibrinogen was also tested. We found that chrysin dose dependently inhibited platelet aggregation and granule secretion induced by collagen, as well as platelet aggregation induced by ADP, thrombin, and U46619. Chrysin also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen. Biochemical analysis revealed that chrysin inhibited collagen-induced activation of Syk, PLCgamma2, PKC, as well as the phosphorylation of Akt and ERK1/2. Additionally, chrysin attenuated phosphorylation of molecules such as FcgammaRIIa, FAK, Akt, and GSK3beta in platelet spreading on immobilized fibrinogen. CONCLUSIONS: Our findings indicate that chrysin suppresses not only integrin alphaIIbbeta3-mediated "inside-out" signaling, but also the "outside-in" signal transmission. This implies that chrysin may represent a potential candidate for an antiplatelet agent. PMID- 27006310 TI - Elastic metamaterials for independent realization of negativity in density and stiffness. AB - In this paper, we present the first realization of an elastic metamaterial allowing independent tuning of negative density and stiffness for elastic waves propagating along a designated direction. In electromagnetic (or acoustic) metamaterials, it is now possible to tune permittivity (bulk modulus) and permeability (density) independently. Apparently, the tuning methods seem to be directly applicable for elastic case, but no realization has yet been made due to the unique tensorial physics of elasticity that makes wave motions coupled in a peculiar way. To realize independent tunability, we developed a single-phased elastic metamaterial supported by theoretical analysis and numerical/experimental validations. PMID- 27006309 TI - MGMT in colorectal cancer: a promising component of personalized treatment. AB - The identification of new, effective drugs is a pressing need in colorectal cancer (CRC) rescue therapy. Data examining O (6)-methylguanine-DNA-methyl transferase (MGMT) and its predictive role in temozolomide (TMZ) treatment in CRC are scarce. In this study, the effect of MGMT status on the cytotoxic sensitivity caused by TMZ was analyzed using cytology proliferation assays in colon cancer cell lines. MGMT protein expression was assessed with immunohistochemistry in 385 patients. Concordance between primary and metastatic sites and the role of MGMT status on survival were statistically analyzed. TMZ sensitivity was significantly affected by the level of MGMT protein expression. Of 385 cases, 13 (3.4 %) demonstrated loss of MGMT expression. However, low MGMT expression levels were significantly more common in signet ring cell carcinomas (p = 0.011). In 111 of 385 cases, the overall concordance of MGMT status between primary tumor and metastatic sites was 66.67 % (kappa = 0.271, p < 0.001). The median progression free survival was significantly different between groups with low or high MGMT expression for the irinotecan-based regimen (p = 0.025), but MGMT protein expression was not observed to be a prognostic factor. In conclusion, MGMT was an important in vitro predictor of TMZ activity in CRC. The rate of MGMT protein loss was low in metastatic CRC patients from China, and MGMT might be more commonly lost in signet ring cell carcinoma. The MGMT status at primary and metastatic sites was consistent, but the power of concordance was poor. Further study into these topics is warranted. PMID- 27006311 TI - Inflammation: Species-specific TLR signalling -- insight into human disease. AB - The selective utilization of IRAK kinases, which are thought to be recruited to MyD88 to form the 'Myddosome', has been shown to differ substantially in mouse and human cells. This finding has important implications for the development of therapeutics for inflammatory and autoimmune disorders associated with Toll-like receptors. PMID- 27006312 TI - Reply. PMID- 27006313 TI - Multiple Xanthogranulomas in an Adult: Known Entity, New Association. AB - BACKGROUND: Multiple xanthogranulomas (XGs) in adults are rare, although an increasing number of case reports are being published. The most frequent association is hematologic malignancies, but the majority of cases remain idiopathic, with occasional spontaneous resolution. OBJECTIVE: The aims of this report are to describe a case of eruptive XG in a woman with a solid neoplasia who was receiving imatinib and to review the literature. METHODS AND RESULTS: This 33-year-old woman had a gastrointestinal stromal tumor. After undergoing surgical removal and being on imatinib for 1 year, the patient developed multiple slightly erythematous papules with an orange hue on the axillary region, trunk, abdomen, and thighs. A biopsy confirmed the diagnosis of XG. CONCLUSION: This is to the investigators' knowledge the first case of eruptive XG in the setting of a solid neoplasia. The possibility of drug-induced XG lesions due to imatinib cannot be excluded. This presentation could be added to the list of associations of adult XG. PMID- 27006314 TI - Successful Transcatheter Aortic Valve Implantation of a Low-Profile Last Generation Aortic Bioprosthesis in a Patient With Coarctation of the Aorta. AB - The application of transcatheter aortic valve implantation (TAVI) in a wider and younger population in the near future makes the need to successfully deal with challenging procedural conditions an imperative. We report a case in which TAVI was successfully conducted in a patient with aortic coarctation using a last generation low-profile bioprosthesis. Despite the fragile aortic wall and its possible abnormal function, a low-profile (14F) CoreValve Evolute R device (Medtronic, Minneapolis, MN) was implanted through the coarctation without complications. Last-generation, low-profile transcatheter implanted aortic valves provide an additional advantage in patients with structural impediments. PMID- 27006315 TI - A Call for Collaboration: Improving Cardiogeriatric Care. AB - With the population aging, there is an exponential increase in the prevalence of cardiovascular disease (CVD). Congestive heart failure (CHF) is considered the "poster child" of the blend of CVD, multimorbidity, and frailty in the aging population. Traditionally, from the cardiologist's point of view, the top multimorbidities in CHF are hypertension, ischemic heart disease, hyperlipidemia, anemia, and diabetes. However, the care of these patients is confounded by common geriatric conditions (multimorbidity, dementia, medication intolerance, frailty) contributing to functional disability, reduced quality of life, and increased hospitalization. Given a 3-fold increase in the number of patients with CHF within the next couple of decades, we must act now. We need to address complex care coordination and integrated disease management as part of the continuum of care, including advance directives and patient preferences. Research and educational curricula must address clinical practice guidelines appropriate for the frail elderly with multimorbidities. Improved care of the older patient with cardiac disease is dependent on a new model of collaboration and teamwork between primary care physician, geriatrician, and cardiologist to accommodate the fundamental heterogeneity of aging and the patients' choices. Collaborative cardiogeriatric clinics have started. The goal of these clinics is to provide integrated care and education for older patients and their caregivers, with the objective of improving quality of life and function. These clinics are also designed to build educational capacity for medical trainees and provide an ongoing research environment. This prototype of a sustainable model will be used to assess methods by which cardiogeriatric clinics could be introduced into standard clinical medical practice. PMID- 27006316 TI - Impact of Crossing Strategy on Intermediate-term Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention. AB - BACKGROUND: There is ongoing controversy about the optimal crossing strategy selection for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), especially regarding the relative merits of antegrade dissection/re-entry and the retrograde approach. METHODS: We retrospectively examined the clinical outcomes of 173 consecutive patients who underwent successful CTO PCI at our institution between January 2012 and March 2015. RESULTS: The mean age was 65 +/- 8 years, and 98% of the patients were men with a high prevalence of diabetes (60%), previous coronary artery bypass grafting (CABG) (31%), and previous PCI (54%). The successful CTO crossing strategy was antegrade wire escalation in 79 patients (45.5%), antegrade dissection/re-entry in 58 patients (33.5%), retrograde wire escalation in 11 patients (6.4%), and retrograde dissection and re-entry in 25 patients (14.5%). The retrograde approach was more commonly used in lesions with interventional collaterals (P < 0.0001), moderate/severe calcification (P = 0.02), blunt stump (P = 0.01), and a higher Japan Chronic Total Occlusion score (P = 0.0002). Use of dissection and re-entry (both antegrade and retrograde) was associated with bifurcation and the distal cap (P = 0.004), longer CTO occlusion length (P < 0.0001), and longer stent length (P < 0.0001). Median follow-up was 11 months. The 12-month incidence of death, myocardial infarction, and the composite of acute coronary syndrome/target lesion revascularization/target vessel revascularization was 2.5%, 4.9%, and 24.4%, respectively, and was similar with intimal and subintimal crossing strategies. CONCLUSIONS: Antegrade dissection/re-entry and retrograde approaches are frequently used during CTO PCI and were associated with similarly favorable intermediate-term outcomes as antegrade wire escalation. PMID- 27006317 TI - Histomorphometric evaluation of a dual acid-etched vs. a chemically modified hydrophilic dual acid-etched implant surface. An experimental study in dogs. AB - OBJECTIVE: The aim of this preclinical in vivo study was to compare histologically and histomorphometrically osseointegration of dual acid-etched vs. hydrophilic implants. MATERIAL AND METHODS: Two pairs of implants (Neodent, Curitiba, Brazil), with same macrogeometry but different surface technology (i) dual acid-etched surface (SAE) treatment with hydrochloric and sulfuric acid followed by microwave treatment and insertion in isotonic saline solution to increase hydrophilicity (SAE-HD) (test, n = 12); (ii) dual SAE (control, n = 12) were installed bilaterally in the proximal tibia of six beagle dogs. Histologic and histomorphometric evaluation was performed after 2 and 4 weeks in vivo, on non-decalcified sections. Percentages of bone-to-implant contact (BIC) and bone density (BD) were estimated and tested for significant differences with the Wilcoxon signed-rank test for paired samples (P < 0.05). RESULTS: In general, new bone formation along and in contact with the implant surface could be observed irrespective of the experimental group and observation period. Most of the bone was woven but small quantities of lamellar bone, mainly in close proximity to the cortex could also be observed. BIC at 2 weeks was 19.57 +/- 13.57 and 20.33 +/- 7.99 (P = 0.75), and at 4 weeks was 42.80 +/- 14.48 and 40.25 +/- 9.45 (P = 0.65) for SAE-HD and SAE implants respectively. BD at 2 weeks was 24.85 +/- 16.31 and 25.66 +/- 8.59 (P = 0.35) and at 4 weeks 44.13 +/- 6.46 and 40.13 +/- 6.46 (P = 0.25) for SAE-HD and SAE implants respectively. CONCLUSION: Bone-to-implant contact and BD increased with time in both SAE-HD and SAE implants. No significant differences were observed between the two different implant surfaces for any of the evaluated parameters and at any observation time-point. PMID- 27006318 TI - Sexual Practices, Fertility Intentions, and Awareness to Prevent Mother-to-Child Transmission of HIV Among Infected Pregnant Women at the Yaounde Central Hospital. AB - INTRODUCTION: The sexual and reproductive health of people living with HIV is fundamental for their well-being. Antiretroviral therapy and reproductive technologies have significantly improved quality of life of people living with HIV in developed countries. In sub-Saharan Africa, the epicenter of HIV, the sexual practices and fertility of women infected with HIV have been understudied. AIM: To assess the sexual behavior, fertility intentions, and awareness of preventing mother-to-child transmission of HIV in pregnant women with HIV negative partners in Yaounde Central Hospital (Yaounde, Cameroon). METHODS: A cross-sectional survey using a semistructured, interviewer-administered questionnaire was conducted at the antenatal unit and HIV clinic in 2014. MAIN OUTCOME MEASURES: Ninety-four pregnant women infected with HIV provided consistent information on (i) sociodemographic characteristics, (ii) sexual and fertility patterns, (iii) awareness of preventing mother-to-child transmission of HIV, and (iv) their unmet needs. RESULTS: Although sexual desire had significantly changed since their HIV diagnosis, the women were highly sexually active. Approximately 19% of women had more than one sexual partner and 40% had regular unprotected sex during the 12-month period before the interviews (P < .0001). Twenty-nine percent of women preferred intermittent sexual intercourse and inconsistent condom use to delay pregnancy, but the abortion rate remained high. Age, marital status, and education affected women's awareness of mother-to child transmission (P < .05); and no association existed between the number of living children and future pregnancies (rs = -0.217; P = .036). CONCLUSION: HIV infected women living with HIV-negative partners in Cameroon expressed high sexual and fertility intentions with several unmet needs, including safer sexual practices and conception. Incorporating and supporting safe sexual educational practices and conception services in maternal care can decrease risky sexual behavior and vertical transmission. PMID- 27006319 TI - Hydrochlorothiazide Potentiates Contractile Activity of Mouse Cavernosal Smooth Muscle. AB - INTRODUCTION: Hydrochlorothiazide has a negative influence on penile erection but little is known about the mechanism(s) involved. AIMS: To characterize the effects of this diuretic on mouse corpus cavernosum (CC) smooth muscle in vitro and ex vivo. METHODS: CC strips of C57BL/6 mice (12-16 weeks old) were mounted in organ baths containing Krebs-Henseleit solution and tissue reactivity was evaluated. Expression of genes encoding diuretic targets and enzymes involved in penile erection were evaluated by polymerase chain reaction. MAIN OUTCOME MEASURES: Stimulation-response curves to phenylephrine (10 nmol/L-100 MUmol/L) or to electrical field stimulation (1-32 Hz) were constructed, with or without hydrochlorothiazide. Strips of CC from mice after long-term hydrochlorothiazide treatment (6 mg/kg/day for 4 weeks) with or without amiloride (0.6 mg/kg/day for 4 weeks) in vivo also were studied. Nitric oxide and Rho-kinase pathways were evaluated. RESULTS: Hydrochlorothiazide (100 MUmol/L) increased the maximum response to phenylephrine by 64% in vitro. This effect was unaffected by the addition of indomethacin (5 MUmol/L) but was abolished by N((omega))-nitro-L arginine methyl ester (100 MUmol/L). Hydrochlorothiazide (100 MUmol/L) potentiated electrical field stimulation-induced contraction in vitro, but not ex vivo. Long-term treatment with hydrochlorothiazide increased the maximum response to phenylephrine by 60% and resulted in a plasma concentration of 500 +/- 180 nmol/L. Amiloride (100MUmol/L) caused rightward shifts in concentration-response curves to phenylephrine in vitro. Long-term treatment with hydrochlorothiazide plus amiloride did not significantly increase the maximum response to phenylephrine (+13%). Reverse transcriptase polymerase chain reaction did not detect the NaCl cotransporter in mouse CC. Hydrochlorothiazide did not change Rho kinase activity, whereas amiloride decreased it in vitro and ex vivo (approximately 18% and 24% respectively). A 40% decrease in Rock1 expression also was observed after long-term treatment with hydrochlorothiazide plus amiloride. CONCLUSION: Hydrochlorothiazide potentiates contraction of smooth muscle from mouse CC. These findings could explain why diuretics such as hydrochlorothiazide are associated with erectile dysfunction. PMID- 27006321 TI - Nanowires with dislocations for ultralow lattice thermal conductivity. AB - Nanostructures grown by screw dislocations have been successfully synthesized in a range of materials, including thermoelectric materials, but the impact of these extended crystallographic defects on thermal properties of these nanostructures is not known. We investigate thermal transport in PbSe and SiGe nanowires storing screw dislocations via equilibrium molecular dynamics simulations. The inherent one dimensionality and the combined presence of a reconstructed surface and dislocation yield ultralow thermal conductivity values. Our simulations suggest that the large dislocation strain field in nanowires may play a key role in suppressing the thermal conductivity of thermoelectric nanomaterials to increase their thermoelectric figure of merit. PMID- 27006320 TI - Access to therapy and therapy outcomes in the Swiss Hepatitis C Cohort Study: a person-centred approach. AB - Socio-demographic and behavioural characteristics are associated with delayed diagnosis and disease progression in HCV-infected persons. However, many analyses focused on single variables rather than groups defined by several variables. We used latent class analysis to study all 4488 persons enrolled in the Swiss Hepatitis C Cohort Study. Groups were identified using predefined variables at enrolment. The number of groups was selected using the Bayesian information criterion. Mortality, loss to follow-up, cirrhosis, treatment status and response to antivirals were analysed using Laplace and logistic regressions. We identified five groups and named them according to their characteristics: persons who inject drugs, male drinkers, Swiss employees, foreign employees and retirees. Two groups did not conform to common assumptions about persons with chronic hepatitis C and were already in an advanced stage of the disease at enrolment: 'male drinkers' and 'retirees' had a high proportion of cirrhosis at enrolment (15% and 16% vs <10.3%), and the shortest time to death (adjusted median time 8.7 years and 8.8 years vs >9.0). 'Male drinkers' also had high substance use, but they were well educated and were likely to be employed. This analysis may help identifying high risk groups which may benefit from targeted interventions. PMID- 27006322 TI - Atrial Fibrillation After Coronary Artery Bypass Surgery: Can Ivabradine Reduce Its Occurrence? AB - INTRODUCTION: We compared the efficacy of perioperative ivabradine, bisoprolol, or both for prevention of postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: We enrolled 740 consecutive patients scheduled for elective CABG with/without valve surgery. Patients were assigned to 1 of 3 protocols: ivabradine given perioperatively (48 hours preoperatively, then 1 week postoperatively) 5 mg bid for 24 hours, then 7.5 mg bid thereafter in patients who can tolerate (group 1, n = 212); bisoprolol given perioperatively 5 mg bid (group 2, n = 288); or both drugs given perioperatively (ivabradine as before + bisoprolol 5 mg once daily) (group 3, n = 240). Cardiac rhythm was continuously monitored for 15 days postoperatively by ambulatory event recorder. Clinical follow-up for the occurrence of arrhythmias was performed for the next 15 days. The primary endpoint was the incidence of AF at 30-day follow-up. Mean age was 56.5 +/- 8.9 years (30.5% females). All patients completed 30-day follow-up. AF occurred in 10.4%. The 3 groups were matched for most baseline characteristics, echocardiographic and angiographic data (P > 0.05 for all). The incidence of AF was significantly lower in group 3 (4.2%), compared with group 1 (15.5%), and group 2 (12.2%), (P < 0.001 both). The duration of stay in the intensive care unit was shorter in group 3 versus group 1 and 2 (P < 0.001 both). CONCLUSION: In patients undergoing elective CABG, adding ivabradine to beta-blockers during the perioperative period was associated with reduced incidence of AF at 30-day follow up, compared with either medication alone. PMID- 27006323 TI - Performance of the Sysmex UF-1000i urine analyser in the rapid diagnosis of urinary tract infections in hospitalized patients. AB - BACKGROUND: Urinary tract infections (UTIs) are the second most frequently encountered nosocomial infectious diseases, and they greatly increase the cost of medical care and prolong the duration of hospital stays. AIM: We aimed to evaluate the performance of the Sysmex UF-1000i analyser for the rapid prediction of UTIs in hospitalized patients with or without indwelling catheters at a comprehensive teaching hospital that encounters complex disease types. METHODS: Urine specimens (n = 1016) were cultured and examined for WBC, RBC, bacteria (BACT) and yeast-like cell (YLC) count using the Sysmex UF-1000i. The results were compared with the urine culture results. Receiver operating characteristic curve analysis was applied to determine BACT and YLC cutoff values for bacterial and fungal UTIs independently. The diagnostic ability of the UF-1000i was also compared for patients with and without indwelling catheters. FINDINGS: A cutoff value of 38.7/MUL was acceptable for ruling out bacterial UTIs. In this setting, we achieved a sensitivity of 90%, a negative predictive value of 94.5%, a false negative rate of 2.85% (29 cases), and avoided culturing in 52% of the samples. The BACT count presented a larger area under the curve for patients with indwelling catheters than for those without (0.939 vs. 0.861); however, no significant difference in the diagnostic ability of the two curves was found. CONCLUSION: The Sysmex UF-1000i analyser could be a reliable method for excluding bacterial UTIs in hospitalized patients with or without urinary catheters and could help clinicians determine whether antibiotic therapy is necessary. PMID- 27006324 TI - Accuracy of the Barrett True-K formula for intraocular lens power prediction after laser in situ keratomileusis or photorefractive keratectomy for myopia. AB - PURPOSE: To compare the accuracy of the Barrett True-K formula with other methods available on the American Society of Cataract and Refractive Surgery (ASCRS) post refractive surgery intraocular lens (IOL) power calculator for the prediction of IOL power after previous myopic laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). SETTING: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, and private practice, Mesa, Arizona, USA. DESIGN: Retrospective case series. METHODS: The accuracy of the Barrett True-K formula was compared with the Adjusted Atlas (4.0 mm zone), Masket, modified-Masket, Wang Koch-Maloney, Shammas, and Haigis-L methods to calculate IOL power. A separate analysis of 2 no-history methods (Shammas and Haigis-L) was performed and compared with the Barrett True-K no-history option. RESULTS: Eighty-eight eyes were available for analysis. The Barrett True-K formula had a significantly smaller median absolute refraction prediction error than all other formulas except the Masket, smaller variances compared with the Wang-Koch-Maloney, Shammas, and Haigis-L, and a greater percentage of eyes within +/-0.50 diopter (D) of predicted error in refraction compared with the Adjusted Atlas, Masket, and modified Masket methods (all P < .05). In eyes with no historical data, the Barrett True-K no-history formula had a significantly smaller median absolute refraction prediction error and a greater percentage of eyes within +/-0.50 D of the predicted error in refraction than the Shammas and the Haigis-L formulas (both P < .05). CONCLUSION: The Barrett True-K formula was either equal to or better than alternative methods available on the ASCRS online calculator for predicting IOL power in eyes with previous myopic LASIK or PRK. PMID- 27006325 TI - Repositioning a decentered intraocular lens with 4 haptics. AB - We describe a technique to reposition a decentered 4-haptic intraocular lens (IOL). Using an ophthalmic viscosurgical device, the haptic with the worst distortion is dissected from the capsular bag and pulled outside the bag. The opposite haptic (180 degrees away) is also dissected and placed in front of the anterior capsule. The remaining 2 haptics are left in the capsular bag. With this repositioning, the 2 haptics in the bag limit the IOL movement, the 2 haptics outside the bag are no longer distorted, and the IOL is centered. We present 2 cases in which this technique was used to reposition decentered 4-haptic IOLs. PMID- 27006326 TI - Opacification of a hydrophilic acrylic intraocular lens with a hydrophobic surface after air injection in Descemet-stripping automated endothelial keratoplasty in a patient with Fuchs dystrophy. AB - A 71-year-old woman with Fuchs endothelial dystrophy in the right eye had uneventful phacoemulsification cataract surgery with implantation of a single piece intraocular lens (IOL) (CT47S) in January 2012. Because of corneal problems and vision loss, uneventful Descemet-stripping automated endothelial keratoplasty (DSAEK) was performed in May 2013. Four months later, a new corneal lamella (repeat DSAEK) was implanted with reinjection of an air bubble into the anterior chamber. Six months after the initial DSAEK, the patient complained of blurred vision. On examination, the cornea was transparent but the IOL presented opacification in the central area. The opacified IOL was explanted and analyzed by light microscopy, which showed the presence of thin granular deposits distributed in an overall round pattern that stained positive for calcium. The opacification of hydrophilic acrylic IOLs is a complication that can occur after uneventful endothelial keratoplasty, especially when rebubbling is necessary. PMID- 27006327 TI - Prediction accuracy of preinstalled formulas on 2 optical biometers. AB - PURPOSE: To evaluate how well partial coherence interferometry (PCI) (IOLMaster) and optical low-coherence reflectometry (OLCR) (Lenstar LS 900) predict postoperative refractions using only the formulas that come preinstalled on the machines. SETTING: Private practice, Saint Joseph, Michigan, USA. DESIGN: Retrospective consecutive case series. METHODS: Eyes were measured with 2 biometers before cataract surgery. Six formulas were ranked by machine. Formulas were also ranked for extremely long and short eyes by averaging the ranks of 6 statistics (mean error, mean absolute error, standard deviation [SD], maximum error, and percentage of eyes within +/-0.5 diopter [D] and +/-1.0 D of prediction). RESULTS: Formulas were ranked by the SD of the prediction errors. The OLCR device outperformed the PCI device using the preinstalled formulas. The Olsen formula performed the best (0.378) but was preinstalled on the OLCR device only. Other formulas had the following SDs (OLCR device first, PCI device second): Haigis (0.393, 0.401), Holladay 1 (0.408, 0.414), Hoffer Q (0.428, 0.432), SRK/T (0.433, 0.440), and SRK II (0.623, 0.633). Rankings for long eye were (first to last) were Olsen, Haigis, SRK/T, Hoffer Q, and Holladay 1. Rankings for short eyes were Olsen, Haigis, Holladay 1, SRK/T, and Hoffer Q. CONCLUSIONS: The OLCR device outperformed the PCI device using the Olsen formula. The Olsen formula also ranked first for short eyes and long eyes. Other formulas performed about the same on both machines. The SRK II formula should be avoided. PMID- 27006328 TI - Sjogren syndrom and mixed nephropathy. Significance of early kidney biopsy. PMID- 27006329 TI - Successfull Simultaneous Pancreas Kidney transplantation in a patient with Congenital Partial Lipodystrophy. PMID- 27006330 TI - Effectiveness of the scheme reimpregnation maintenance schedule vs. ceftazidime/cephalothin in dialysis patients with peritonitis. PMID- 27006331 TI - Sexually active bucks are efficient to stimulate female ovulatory activity during the anestrous season also under temperate latitudes. AB - Goats are seasonal breeders and photoperiod is the main cue controlling the onset and offset of the breeding season. Nevertheless introducing a sexually active buck in a group of females during anestrous can stimulate their reproductive function and induce ovulation. This "male-effect" is very efficient under subtropical latitudes, when using sexually active males previously stimulated by a photoperiodic treatment. However, there is less evidence of its feasibility under temperate latitudes where the more important variation in day length could be responsible for a stronger inhibition of female sexual activity. The aim of this study was therefore to determine whether intense sexual activity can be induced in alpine bucks during the non-breeding season by a long-day treatment under temperate latitude and if these males could be used to produce an efficient male-effect. Bucks (n=21) were divided in two groups, one submitted to a photoperiodic treatment from November 1st to January 15th and then switched to natural photoperiod, while the other group remained entirely under the natural photoperiod. The ones submitted to this light treatment exhibit higher testicular volume and testosterone level 6 weeks after the end of the treatment. At the end of March, bucks were used to stimulate anestrous does (n=41) continuously for 15 days. We showed that (a) light treatment was efficient to induce an increase of sexual activity in bucks and (b) that the introduction of stimulated bucks among females induced a significantly higher proportion of ovulation in anestrous does than control bucks (86% vs 5%). Our results indicate that under temperate latitudes induction of ovulation in females during the anestrous season is feasible using bucks treated with long-days during winter. PMID- 27006332 TI - The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer. AB - BACKGROUND: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naive metastatic castration-resistant prostate cancer. OBJECTIVE: To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. DESIGN, SETTING, AND PARTICIPANTS: One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (<4 bone metastases; n=867), high-volume bone disease (>=4 bone metastases; n=850), lymph node only disease (n=195). INTERVENTION: Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. RESULTS AND LIMITATIONS: Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11 0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (<1) across all disease subgroups, although 95% CI was >1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease. CONCLUSIONS: Enzalutamide provided clinically significant benefits in men with chemotherapy-naive metastatic castration resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. PATIENT SUMMARY: Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease or widespread bone disease-benefitted from enzalutamide, an active well-tolerated therapy. PMID- 27006333 TI - Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan. AB - Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. PMID- 27006334 TI - Relationship between IL-10 gene polymorphisms and the risk of non-Hodgkin lymphoma: A meta-analysis. AB - OBJECTIVES: The purpose of this study was to explore whether interleukin-10 (IL 10) gene promoter polymorphisms and their haplotypes contribute to the incidence of non-Hodgkin lymphoma (NHL). METHODS: A meta-analysis was conducted on the associations of the IL-10-3575T/A, -1082 G/A, -819 C/T, -592C/A polymorphisms and the haplotypes with NHL. RESULTS: A total of 23 studies involving 21,563 NHL patients and 23,837 controls were included in the meta-analysis. Pooled results indicated that IL-10-3575T/A was associated with an increased risk of NHL based on the dominant model (OR: 1.095, 95% CI: 1.020-1.178), similar results were found for -1082A/G in the heterozygous and recessive models (OR: 1.042, 95% CI: 1.012-1.074; and OR: 1.034, 95% CI: 1.011-1.057, respectively). In the ethnic subgroup analysis, -3575T/A had an increased risk of NHL in Caucasians based on the homozygous model (OR: 1.071, 95% CI: 1.001-1.146), and similar results were found for -1082A/G in the heterozygous and recessive models (OR: 1.041, 95% CI: 1.009-1.075; and OR: 1.031, 95% CI: 1.008-1.055, respectively). When stratified by subtypes, -3575T/A and -1082A/G polymorphisms were found significant association with an increased risk of B cell lymphoma, specifically diffuse large B-cell lymphoma (DLBCL). Moreover, -3575T/A was associated with an increased risk of follicular lymphoma (FL) in the homozygous and recessive models. Furthermore, we observed that significantly increased risk of NHL and DLBCL were associated with the A-G-C-C haplotype (IL-10-3575T/A, -1082A/G, -819C/T and -592C/A), and a decreased risk of DLBCL subtype was associated with the T-A-C-C haplotype. CONCLUSIONS: IL-10-3575T/A and -1082A/G polymorphisms were associated with altered NHL susceptibility, especially for Caucasians and B cell lymphoma. IL-10 (-3575T/A, -1082A/G, -819C/T and -592C/A) haplotype were associated with NHL and DLBCL subtype. PMID- 27006335 TI - A systemic study on key parameters affecting nanocomposite coatings on magnesium substrates. AB - Nanocomposite coatings offer multiple functions simultaneously to improve the interfacial properties of magnesium (Mg) alloys for skeletal implant applications, e.g., controlling the degradation rate of Mg substrates, improving bone cell functions, and providing drug delivery capability. However, the effective service time of nanocomposite coatings may be limited due to their early delamination from the Mg-based substrates. Therefore, the objective of this study was to address the delamination issue of nanocomposite coatings, improve the coating properties for reducing the degradation of Mg-based substrates, and thus improve their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs). The surface conditions of the substrates, polymer component type of the nanocomposite coatings, and post-deposition processing are the key parameters that contribute to the efficacy of the nanocomposite coatings in regulating substrate degradation and bone cell responses. Specifically, the effects of metallic surface versus alkaline heat-treated hydroxide surface of the substrates on coating quality were investigated. For the nanocomposite coatings, nanophase hydroxyapatite (nHA) was dispersed in three types of biodegradable polymers, i.e., poly(lactic-co-glycolic acid) (PLGA), poly(l-lactic acid) (PLLA), or poly(caprolactone) (PCL) to determine which polymer component could provide integrated properties for slowest Mg degradation. The nanocomposite coatings with or without post-deposition processing, i.e., melting, annealing, were compared to determine which processing route improved the properties of the nanocomposite coatings most significantly. The results showed that optimizing the coating processes addressed the delamination issue. The melted then annealed nHA/PCL coating on the metallic Mg substrates showed the slowest degradation and the best coating adhesion, among all the combinations of conditions studied; and, it improved the adhesion density of BMSCs. This study elucidated the key parameters for optimizing nanocomposite coatings on Mg-based substrates for skeletal implant applications, and provided rational design guidelines for the nanocomposite coatings on Mg alloys for potential clinical translation of biodegradable Mg based implants. STATEMENT OF SIGNIFICANCE: This manuscript describes the systemic optimization of nanocomposite coatings to control the degradation and bioactivity of magnesium for skeletal implant applications. The key parameters influencing the integrity and functions of the nanocomposite coatings on magnesium were identified, guidelines for the optimization of the coatings were established, and the benefits of coating optimization were demonstrated through reduced magnesium degradation and increased bone marrow derived mesenchymal stem cell (BMSC) adhesion in vitro. The guidelines developed in this manuscript are valuable for the biometal field to improve the design of bioresorbable implants and devices, which will advance the clinical translation of magnesium-based implants. PMID- 27006336 TI - Greater Fall Risk in Elderly Women Than in Men Is Associated With Increased Gait Variability During Multitasking. AB - OBJECTIVE: As 90% of fractures are caused by falls, and as fractures are more common in elderly women than in elderly men, a better understanding of potential sex differences in fall rates and underlying mechanisms is needed. The purpose of this study was to determine whether women are more prone than men to falling, and to evaluate whether the risk of falling is associated with variations in gait patterns. DESIGN, SETTING, AND PARTICIPANTS: The cohort for this prospective observational study consisted of 1390 community-dwelling men and women aged 70 years, examined in a health survey between July 2012 and November 2014. MEASUREMENTS: Gait patterns were measured using a computerized walkway system during normal-speed, fast-speed, and dual-task trials. Triaxial accelerometers were used to collect objective data on physical activity, and self-reported fall data were collected by telephone 6 and 12 months after examination. Incident low energy falls were defined as unexpected events in which participants came to rest on the ground. RESULTS: During the follow-up period, 148 study participants (88 women, 60 men; P = .01) reported falls. After adjusting for multiple confounders, including objective measures of physical activity, socioeconomic factors, cardiovascular disease, and cognitive function, the odds ratio for falling in women was 1.49 (95% confidence interval [CI] 1.02-2.19). Variations in gait pattern were significantly (20%-40%) increased in fallers compared with nonfallers during the dual-task trial for step width, step length, stride length, step time, stance time, stride velocity, and single support time (all P < .05). Furthermore, women showed 15% to 35% increased variability in all of these gait parameters during the dual-task trial compared with men (all P < .01). CONCLUSION: In the present cohort, 70-year-old women were at greater risk of falls compared with their male counterparts. This increased risk was associated with increased variation in gait pattern during dual-task activities, and may contribute to women's greater fracture risk compared with men. PMID- 27006337 TI - [Tissue expansion in children: Indications and management of complications. A 10 year experience]. AB - INTRODUCTION: Tissue expansion is a plastic surgery technique which enables optimal quality and skin surface reconstruction in case of soft tissue defect. Despite the good results obtained, both from a functional and aesthetic point of view, there is a high rate of complications whose management seems to be essential to ensure satisfactory results. PATIENTS AND METHODS: We retrospectively reviewed the medical files of 45 children treated in our department between 2002 and 2012: 73 expanders were placed during 51 protocols. RESULTS: The studied protocols gathered a large variety of situations. Varied pathologies were treated: burn sequelae (39 %), giant congenital naevus (GCN) (27 %), scars (20 %), hamartoms (8 %), cutis aplasia (6 %), as well as diverse sites: scalp (45 %), trunk (35 %), head and neck (8 %), lower extremity (8 %), upper extremity (4 %). Complications occurred in 17 protocols representing 26 % of total expanders. GCN is a pathology with a significantly lower complication rate (P=0.013) whereas trunk is an anatomical location with a significantly higher complication rate (P=0.026). Overall, 84 % of reconstructions were evaluated as having a good result. This rate reached 76 % for complicated protocols. CONCLUSION: Tissue expansion in paediatric patients remains an efficient therapy in order to achieve a satisfactory reconstruction. Despite a high complication rate, good results can be obtained even in those complicated cases as long as they are well managed and anticipated. We also think that specific paediatric material would help to reduce supervention of some complications. PMID- 27006340 TI - Correction. PMID- 27006338 TI - Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients. AB - Anti-cancer drugs often increase reactive oxygen species (ROS) and cause DNA damage. Here, we highlight a new cross talk between chronic oxidative stress and the histone variant H2AX, a key player in DNA repair. We observe that persistent accumulation of ROS, due to a deficient JunD-/Nrf2-antioxidant response, reduces H2AX protein levels. This effect is mediated by an enhanced interaction of H2AX with the E3 ubiquitin ligase RNF168, which is associated with H2AX poly ubiquitination and promotes its degradation by the proteasome. ROS-mediated H2AX decrease plays a crucial role in chemosensitivity. Indeed, cycles of chemotherapy that sustainably increase ROS reduce H2AX protein levels in Triple-Negative breast cancer (TNBC) patients. H2AX decrease by such treatment is associated with an impaired NRF2-antioxidant response and is indicative of the therapeutic efficiency and survival of TNBC patients. Thus, our data describe a novel ROS mediated regulation of H2AX turnover, which provides new insights into genetic instability and treatment efficacy in TNBC patients. PMID- 27006339 TI - Initial development of patient-reported instrument assessing harm, efficacy, and misuse of long-term opioid therapy. AB - Guidelines on long-term opioid therapy recommend frequent reassessment of harm, efficacy, and misuse of these potentially harmful and sometimes ineffective medications. In primary care, there is a need for a brief, patient-reported instrument. This report details the initial steps in the development of such an instrument. An interdisciplinary team of clinician-scientists performed four discrete steps in this study: (1) conceptualization of the purpose and function of the instrument, (2) assembly of an item pool, (3) expert rating on which items were most important to include in the instrument, and (4) modification of expert selected items based on a reading level check and cognitive interviews with patients. A diverse panel of 47 subject matter experts was presented with 69 items to rate on a 1-9 scale in terms of importance for inclusion in the instrument. The panel highly rated 37 items: 8 related to harm, 4 related to efficacy, and 25 related to misuse. These 37 items were then tested for patient comprehension and modified as needed. Next steps in development will include further item reduction, testing against a gold standard, and assessment of the instrument's effect on clinical outcomes. PMID- 27006341 TI - Cohort profile of the UK Biobank: diagnosis and characteristics of cerebrovascular disease. AB - PURPOSE: The UK Biobank is a large-scale biomedical resource, containing sociodemographic and medical information, including data on a previous diagnosis of stroke or transient ischaemic attack (TIA). We described these participants and their medication usage. PARTICIPANTS: We identified participants who either self-reported or were identified from a nurse-led interview, having suffered a stroke or a TIA and compared them against participants without stroke ort TIA. We assessed their risk factor burden (sex, age, deprivation, waist to hip ratio (WHR), hypertension, smoking, alcohol intake, diabetes, physical exercise and oral contraception use (oral contraceptive pill, OCP)) and medication usage. FINDINGS TO DATE: We studied 502,650 people (54.41% women), 6669 (1.23%) participants self-reported a stroke. The nurse-led interview identified 7669 (1.53%) people with stroke and 1781 (0.35%) with TIA. Hypertension, smoking, higher WHR, lower alcohol consumption and diabetes were all more common in people with cerebrovascular disease (p<0.0001 for each). Women with cerebrovascular disease were less likely to have taken the OCP (p=0.0002). People with cerebrovascular disease did more exercise (p=0.03). Antithrombotic medication was taken by 81% of people with stroke (both self-report and nurse-led responders) and 89% with TIA. For self-reported stroke, 63% were taking antithrombotic and cholesterol medications, 54% taking antithrombotic and antihypertensive medications and 46% taking all 3. For the nurse-led interview and TIA, these figures were 65%, 54% and 46%, and 70%, 53% and 45%, respectively. FUTURE PLANS: The UK Biobank provides a large, generalisable and contemporary data source in a young population. The characterisation of the UK Biobank cohort with cerebrovascular disease will form the basis for ongoing research using this data source. PMID- 27006342 TI - Potential workload in applying clinical practice guidelines for patients with chronic conditions and multimorbidity: a systematic analysis. AB - OBJECTIVES: To describe the potential workload for patients with multimorbidity when applying existing clinical practice guidelines. DESIGN: Systematic analysis of clinical practice guidelines for chronic conditions and simulation modelling approach. DATA SOURCES: National Guideline Clearinghouse index of US clinical practice guidelines. STUDY SELECTION: We identified the most recent guidelines for adults with 1 of 6 prevalent chronic conditions in primary care (ie hypertension, diabetes, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), osteoarthritis and depression). DATA EXTRACTION: From the guidelines, we extracted all recommended health-related activities (HRAs) such as drug management, self-monitoring, visits to the doctor, laboratory tests and changes of lifestyle for a patient aged 45-64 years with moderate severity of conditions. SIMULATION MODELLING APPROACH: For each HRA identified, we performed a literature review to determine the potential workload in terms of time spent on this HRA. Then, we used a simulation modelling approach to estimate the potential workload needed to comply with these recommended HRAs for patients with several of these chronic conditions. RESULTS: Depending on the concomitant chronic condition, patients with 3 chronic conditions complying with all the guidelines would have to take a minimum of 6 to a maximum of 13 medications per day, visit a health caregiver a minimum of 1.2 to a maximum of 5.9 times per month and spend a mean (SD) of 49.6 (27.3) to 71.0 (34.5) h/month in HRAs. The potential workload increased greatly with increasing number of concomitant conditions, rising to 18 medications per day, 6.6 visits per month and 80.7 (35.8) h/month in HRAs for patients with 6 chronic conditions. PMID- 27006343 TI - 'Why should I worry, since I have healthy feet?' A qualitative study exploring barriers to use of footwear among rural community members in northern Ethiopia. AB - OBJECTIVE: To explore the influence of personal, cultural and socioeconomic factors related to footwear use and non-use in northern Ethiopia. DESIGN: A qualitative study was conducted using focus group discussions and in-depth individual interviews. Data were collected using semistructured interview guides. SETTING: The study was conducted in East and West Gojjam Zones, Amhara region, northwest Ethiopia. PARTICIPANTS: A total of 91 individuals from 4 target groups participated in individual and group interviews: (1) non-affected community leaders including Idir (a form of social insurance) leaders, school principals, kebele (the lowest administrative unit) officials, health professionals, teachers, merchants and religious leaders; (2) affected men and women; (3) non affected men and women not in leadership positions; and (4) school children (both male and female). RESULTS: Participants perceived a range of health benefits from donning footwear, including protection against injury and cold. Various types of shoes are available within the community, and their use varied depending on the nature of activities and the season. Personal and socioeconomic barriers hindered the desire to consistently use footwear. Widely established barefoot traditions and beliefs that footwear is uncomfortable, heavy and may weaken the feet have made the regular use of footwear uncommon. Economic constraints were also mentioned as hindering ownership and use of footwear. Distance from places where shoes could be bought also contributed to limited access. Cultural influences promoting gender inequality resulted in women being least able to access shoes. CONCLUSIONS: We identified several individual, cultural and socioeconomic barriers that influence individuals' decisions about and use of footwear in rural northern Ethiopia. Promoting education on the health benefits of footwear, curbing podoconiosis-related misconceptions and integrating these with economic empowerment programmes, may all improve the use of footwear. PMID- 27006344 TI - Factors affecting Japanese retirees' healthcare service utilisation in Malaysia: a qualitative study. AB - OBJECTIVE: While living overseas in another culture, retirees need to adapt to a new environment but often this causes difficulties, particularly among those elderly who require healthcare services. This study examines factors affecting healthcare service utilisation among Japanese retirees in Malaysia. DESIGN: We conducted 6 focus group discussions with Japanese retirees and interviewed 8 relevant medical services providers in-depth. Guided by the Andersen Healthcare Utilisation Model, we managed and analysed the data, using QSR NVivo 10 software and the directed content analysis method. SETTING: We interviewed participants at Japan Clubs and their offices. PARTICIPANTS: 30 Japanese retirees who live in Kuala Lumpur and Ipoh, and 8 medical services providers. RESULTS: We identified health beliefs, medical symptoms and health insurance as the 3 most important themes, respectively, representing the 3 dimensions within the Andersen Healthcare Utilisation Model. Additionally, language barriers, voluntary health repatriation to Japan and psychological support were unique themes that influence healthcare service utilisation among Japanese retirees. CONCLUSIONS: The healthcare service utilisation among Japanese retirees in Malaysia could be partially explained by the Andersen Healthcare Utilisation Model, together with some factors that were unique findings to this study. Healthcare service utilisation among Japanese retirees in Malaysia could be improved by alleviating negative health beliefs through awareness programmes for Japanese retirees about the healthcare systems and cultural aspects of medical care in Malaysia. PMID- 27006345 TI - Protocol for the development and validation of a questionnaire to assess concerning behaviours and mental health in individuals with autism spectrum disorders: the Assessment of Concerning Behaviour (ACB) scale. AB - INTRODUCTION: Co-occurring psychiatric conditions and concerning behaviours are prevalent in individuals with autism spectrum disorders (ASD), and are likely to be detrimental to functioning and long-term outcomes. The cognitive rigidity and deficits in emotional literacy and verbal behaviour that commonly occur in ASD can adversely affect clinicians' confidence to identify concerning behaviours and mental health problems. There is a need to develop a measure that is tailored towards individuals with ASD, and differentiates between symptoms of psychopathology and core ASD symptoms. Furthermore, it should be modified to capture internalising symptoms that individuals with ASD may find difficult or be unable to verbalise. This protocol describes the intended development and validation of the Assessment of Concerning Behaviour (ACB) scale. The ACB will aim to be a multidimensional measure of concerning behaviours in ASD incorporating self-report, parent/carer, teacher/employer and clinician report versions that can be used across the lifespan and spectrum of intellectual ability. METHODS AND ANALYSIS: This study will be guided by the methods described in the US Food and Drug Administration Guidance for Industry Patient-reported Outcome Measures. A literature review, cognitive interviews and focus groups with individuals who have experience of working or living with ASDs will be used for item generation. A sample of children and adults with ASD will complete the ACB, in addition to other gold standard measures of concerning behaviour in order to establish the initial psychometric properties of the scale. ETHICS AND DISSEMINATION: This study has received ethical approval from the NHS Research Ethics Committee: London-Camden and King's Cross (ref: 15/LO/0085). Study findings will be disseminated to healthcare professionals and scientists in the field through publication in peer-reviewed journals and conference presentations. PMID- 27006346 TI - Value of systematic detection of physical child abuse at emergency rooms: a cross sectional diagnostic accuracy study. AB - OBJECTIVES: The aim of our diagnostic accuracy study Child Abuse Inventory at Emergency Rooms (CHAIN-ER) was to establish whether a widely used checklist accurately detects or excludes physical abuse among children presenting to ERs with physical injury. DESIGN: A large multicentre study with a 6-month follow-up. SETTING: 4 ERs in The Netherlands. PARTICIPANTS: 4290 children aged 0-7 years attending the ER because of physical injury. All children were systematically tested with an easy-to-use child abuse checklist (index test). A national expert panel (reference standard) retrospectively assessed all children with positive screens and a 15% random sample of the children with negative screens for physical abuse, using additional information, namely, an injury history taken by a paediatrician, information provided by the general practitioner, youth doctor and social services by structured questionnaires, and 6-month follow-up information. MAIN OUTCOME MEASURE: Physical child abuse. SECONDARY OUTCOME MEASURE: Injury due to neglect and need for help. RESULTS: 4253/4290 (99%) parents agreed to follow-up. At a prevalence of 0.07% (3/4253) for inflicted injury by expert panel decision, the positive predictive value of the checklist was 0.03 (95% CI 0.006 to 0.085), and the negative predictive value 1.0 (0.994 to 1.0). There was 100% (93 to 100) agreement about inflicted injury in children, with positive screens between the expert panel and child abuse experts. CONCLUSIONS: Rare cases of inflicted injury among preschool children presenting at ERs for injury are very likely captured by easy-to-use checklists, but at very high false-positive rates. Subsequent assessment by child abuse experts can be safely restricted to children with positive screens at very low risk of missing cases of inflicted injury. Because of the high false positive rate, we do advise careful prior consideration of cost-effectiveness and clinical and societal implications before de novo implementation. PMID- 27006348 TI - Oronasal and Tracheostomy Delivery of Soft Mist and Pressurized Metered-Dose Inhalers With Valved Holding Chamber. AB - BACKGROUND: Some pediatric tracheostomized patients who receive inhaled drugs undergo decannulation, and it is unknown whether the dose has to be adjusted. Pressurized metered-dose inhalers (pMDIs) and soft mist inhalers (SMIs) used with valved holding chambers (VHCs) made of non-electrostatic material are available. We hypothesized that using an SMI and changing the delivery route from tracheostomy to oronasal would increase lung dose. METHODS: Four units of a metallic VHC were studied with albuterol hydrofluoroalkane (pMDI) and albuterol/ipratropium bromide with an SMI using an anatomically correct in vitro model of a 5-y-old spontaneously breathing tracheostomized child. The drug was captured in a filter and was termed lung dose. We tested breathing patterns with tidal volumes of 50, 155, and 300 mL. A mask and a special adapter were used as interfaces for oronasal and tracheostomy delivery, respectively. Spectrophotometry (276 nm) was used to determine albuterol concentration. RESULTS: The use of SMI resulted in a higher lung dose than the pMDI for all tested conditions except delivery through tracheostomy with tidal volume of 155 mL (P = .69). Switching from oronasal to tracheostomy delivery increased the lung dose for all tested conditions except for the pMDI with the 300-mL tidal volume (P = .83). The use of SMI resulted in higher deposition in the tracheostomy tube than the pMDI. CONCLUSIONS: In general, an SMI delivers a higher lung dose than a pMDI when using a metallic spacer during oronasal and tracheostomy route with the latter providing a higher lung dose. PMID- 27006347 TI - Investigating kidney donation as a risk factor for hypertension and microalbuminuria: findings from the Swiss prospective follow-up of living kidney donors. AB - OBJECTIVES: To assess the role of nephrectomy as a risk factor for the development of hypertension and microalbuminuria. DESIGN: Prospective, long-term follow-up study. SETTING: Swiss Organ Living-Donor Health Registry. PARTICIPANTS: All living kidney donors in Switzerland between 1993 and 2009. INTERVENTIONS: Data on health status and renal function before 1 year and biennially after donation were collected. PRIMARY AND SECONDARY OUTCOME MEASURES: Comparison of 1 year and 5-year occurrences of hypertension among normotensive donors with 1-year and 5-year estimates from the Framingham hypertension risk score. Multivariate random intercept models were used to investigate changes of albumin excretion after donation, correcting for repeated measurements and cofactors such as age, male gender and body mass index. RESULTS: A total of 1214 donors contributed 3918 data entries with a completed biennial follow-up rate of 74% during a 10-year period. Mean (SD) follow-up of donors was 31.6 months (34.4). Median age at donation was 50.5 years (IQR 42.2-58.8); 806 donors (66.4%) were women. Donation increased the risk of hypertension after 1 year by 3.64 (95% CI 3.52 to 3.76; p<0.001). Those participants remaining normotensive 1 year after donation return to a risk similar to that of the healthy Framingham population. Microalbuminuria before donation was dependent on donor age but not on the presence of hypertension. After nephrectomy, hypertension became the main driver for changes in albumin excretion (OR 1.19; 95% CI 0.13 to 2.25; p=0.03) and donor age had no effect. CONCLUSIONS: Nephrectomy propagates hypertension and increases susceptibility for the development of hypertension-induced microalbuminuria. PMID- 27006349 TI - Tracheostomy in Infants With Congenital Heart Disease: A Nationwide Population Based Study in Taiwan. AB - BACKGROUND: This study aimed to use the National Health Insurance Research Database in Taiwan to examine the risk factors for tracheostomy in infants with congenital heart disease (CHD) and to evaluate the associated mortality risk in those who received a tracheostomy. METHODS: The study was conducted between 2000 and 2011 with infants assigned to either a CHD group (34,943 subjects) or an age- and sex-matched control group (136,600 subjects). We then performed descriptive, logistic regression, Kaplan-Meier, and Cox regression analyses for the investigation. RESULTS: Infants with CHD had an increased risk of tracheostomy (adjusted hazard ratio [HR], 6.67, 95% CI 4.40-10.10). Congenital airway anomaly (adjusted odds ratio [OR], 15.25, 95% CI 10.56-22.02), neuromuscular impairment (adjusted OR 6.24, 95% CI 4.35-8.94), and time (0-3 y) after CHD diagnosis (adjusted OR 3.27, 95% CI 2.19-4.89) were most highly correlated with tracheostomy placement. The mortality risk was increased in infants with CHD and a tracheostomy even after adjusting for confounders (adjusted HR 3.88, 95% CI 2.96-5.08). Mortality risk (adjusted HR and 95% CI) increased by 2.06 (1.56 2.71), 7.19 (2.42-21.38), and 14.76 (1.46-149.69) after 0-3, 4-7, and 8-11 y of follow-up, respectively. CONCLUSIONS: Infants with CHD had an increased risk of undergoing tracheostomy. The mortality risk is significantly increased in infants with CHD and tracheostomy, and the risk increases progressively with time. Further studies are warranted to clarify the mechanisms underlying the risks associated with tracheostomy. PMID- 27006350 TI - Perception of Exercise-Induced Bronchoconstriction in College Athletes. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) can lead to long-term respiratory illness and even death. EIB prevalence rates are both high and variable in college athletes. Also, prevalence rates may be underestimated due to ineffective screening. The purpose of this study is to investigate the prevalence of EIB and the perceived impact of EIB in college athletes via a self-report questionnaire. METHODS: A self-report EIB questionnaire was administered to college athletes on 8 different sports teams. Information collected was used to identify athletes who self-reported: (1) a history of EIB and/or asthma, (2) respiratory symptoms during exercise, (3) medication use, and (4) concern about EIB. RESULTS: Results showed that 56 of 196 athletes (28.6%) self-reported a history of EIB or asthma. Over half (52%) reported a history of EIB/asthma or current EIB symptoms. Forty-six of the 140 athletes (32.9%) who did not report a history of EIB or asthma indicated symptoms of EIB during sports, training, or exercise. Fourteen of 56 athletes (25%) self-reporting a history of EIB or asthma did not report the use of a respiratory medication. Nineteen of 196 athletes (9.7%) reported being concerned that EIB was adversely affecting their sports performance. CONCLUSIONS: College athletes self-report a high prevalence of EIB or asthma. Although college athletes may not report a history of EIB or asthma, they indicate symptoms of EIB. A majority of athletes reported a history or current symptoms related to EIB or asthma. Many athletes with a history of EIB or asthma are not taking any asthma medication. Last, athletes report concern about EIB adversely affecting their sports performance. More work is needed using a combination of a screening questionnaire and standardized EIB testing to develop a validated tool for accurately screening and diagnosing EIB in college athletes. PMID- 27006351 TI - Blunted Hypercapnic Respiratory Drive Response in Subjects With Late-Onset Pompe Disease. AB - BACKGROUND: Patients with late-onset Pompe disease develop progressive hypercapnic respiratory failure that can be disproportionate to the respiratory muscle compromise and/or thoracic restriction. Although recent studies have reported the presence of a blunted hypercapnic respiratory response in some subjects with neuromuscular disorders and chronic hypercapnia, no study has evaluated the integrity of the respiratory drive in subjects with late-onset Pompe disease. Thus, we endeavor to determine the CO2 rebreathing response in subjects with late-onset Pompe disease. METHODS: Respiratory muscle strength was assessed by measuring the maximum inspiratory pressure, and the maximum expiratory pressure. The maximum inspiratory pressure reflects the strength of the diaphragm and other inspiratory muscles, whereas the maximum expiratory pressure reflects the strength of the abdominal muscles and other expiratory muscles. We studied the hypercapnic drive response (measured as the ratio of the change in airway-occlusion pressure 0.1 s after the start of inspiration and end tidal PCO2 in 13 subjects with late-onset Pompe disease and 51 healthy controls. RESULTS: Overall inspiratory muscle strength was within normal limits or slightly diminished in the late-onset Pompe disease group. Five subjects (38.5%) were chronically hypercapnic, and 9 (69.2%) had an increased breath-holding time. Compared with controls, the change in airway-occlusion pressure 0.1 s/change in end-tidal CO2 pressure slope (hypercapnic respiratory drive) was lower in the late-onset Pompe disease group (median 0.050 [interquartile range 0.027-0.118] vs 0.183 [0.153-0.233], P < .001). Nine subjects (69.2%) had a blunted change in airway-occlusion pressure 0.1 s/change in end-tidal carbon dioxide pressure slope. CONCLUSIONS: Subjects with late-onset Pompe disease had an impaired hypercapnic respiratory drive response. The clinical impact of this phenomenon in this subject subset deserves further investigation. PMID- 27006352 TI - Cohort Profile: The Health Outcomes and Measures of the Environment (HOME) study. PMID- 27006353 TI - Managing the Clues in Cancer Care. PMID- 27006354 TI - Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool. AB - PURPOSE: Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. METHODS: Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. RESULTS: Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. CONCLUSION: The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. PMID- 27006355 TI - Feasibility Study of an Electronic Interface Between Internet-Based Survivorship Care Plans and Electronic Medical Records. AB - PURPOSE: Survivorship care plans (SCPs) are recommended for all cancer survivors. Myriad barriers to implementation exist. This study was performed to evaluate the feasibility of interface development between an SCP and an electronic medical record (EMR). METHODS: An information technology application was developed to extract data from the EMR in use at our center (Epic). Data were transferred to autopopulate an Internet-based tool for creation of SCPs (LIVESTRONG Care Plan) that had been previously used for the creation of more than 35,000 plans. RESULTS: Data (demographic characteristics, surgeries, chemotherapy drugs, radiation site) were extracted from the EMR and transferred to the care plan platform, without transfer of protected health information. Care plans were created and transferred back to the EMR. During clinical testing, SCPs were created by nurse practitioners during scheduled clinic visits for 146 sequential, eligible patients (67% breast cancer, 33% colorectal cancer). All patients received completed care for a single cancer diagnosis at our institution. All data points that were automatically populated were reviewed by practitioners, and missing/blank data fields were populated manually when necessary. Data entered into generated care plans were accurate in 97% of audited cases, and the process of care plan generation could be completed in < 1 minute. CONCLUSION: This is a feasible solution for the autopopulation of SCPs from the EMR. It represents a future methodology through which widespread implementation of SCPs may be undertaken. Future directions include further clinical testing, assessment of provider-perceived usefulness, and integration into routine clinical care. PMID- 27006357 TI - The National Practice Benchmark for Oncology: 2015 Report for 2014 Data. AB - The National Practice Benchmark (NPB) is a unique tool used to measure oncology practices against others across the country in a meaningful way despite variations in practice demographics, size, and setting. In today's challenging economic environment, each practice positions service offerings and competitive advantages to attract patients. Although the data in the NPB report are primarily reported by community oncology practices, the business structure and arrangements with regional health care systems are also reflected in the benchmark report. The ability to produce detailed metrics is an accomplishment of excellence in business and clinical management. With these metrics, a practice should be able to measure and analyze its current business practices and make appropriate changes, if necessary. In this report, we build on the foundation initially established by Oncology Metrics (acquired by Flatiron Health in 2014) over years of data collection and refine definitions to deliver the NPB, which is uniquely meaningful in the oncology market. PMID- 27006358 TI - Board-Certified Oncology Pharmacists: Their Potential Contribution to Reducing a Shortfall in Oncology Patient Visits. AB - PURPOSE: With an aging US population, the number of patients who need cancer treatment will increase significantly by 2020. On the basis of a predicted shortage of oncology physicians, nonphysician health care practitioners will need to fill the shortfall in oncology patient visits, and nurse practitioners and physician assistants have already been identified for this purpose. This study proposes that appropriately trained oncology pharmacists can also contribute. The purpose of this study is to estimate the supply of Board of Pharmacy Specialties certified oncology pharmacists (BCOPs) and their potential contribution to the care of patients with cancer through 2020. METHODS: Data regarding accredited oncology pharmacy residencies, new BCOPs, and total BCOPs were used to estimate oncology residencies, new BCOPs, and total BCOPs through 2020. A Delphi panel process was used to estimate patient visits, identify patient care services that BCOPs could provide, and study limitations. RESULTS: By 2020, there will be an estimated 3,639 BCOPs, and approximately 62% of BCOPs will have completed accredited oncology pharmacy residencies. Delphi panelists came to consensus (at least 80% agreement) on eight patient care services that BCOPs could provide. Although the estimates given by our model indicate that BCOPs could provide 5 to 7 million 30-minute patient visits annually, sensitivity analysis, based on factors that could reduce potential visit availability resulted in 2.5 to 3.5 million visits by 2020 with the addition of BCOPs to the health care team. CONCLUSION: BCOPs can contribute to a projected shortfall in needed patient visits for cancer treatment. BCOPs, along with nurse practitioners and physician assistants could substantially reduce, but likely not eliminate, the shortfall of providers needed for oncology patient visits. PMID- 27006359 TI - Radiation Oncology Practice: Adjusting to a New Reimbursement Model. AB - PURPOSE: Use of hypofractionation is increasing in radiation oncology because of several factors. The effects of increasing hypofractionation use on departments and staff currently based on fee-for-service models are not well studied. METHODS: We modeled the effects of moving to hypofractionation for prostate, breast, and lung cancer and palliative treatments in a typical-sized hospital based radiation oncology department. Year 2015 relative value unit (RVU) data were used to determine changes in reimbursement. The change in number of fractions was used to model the effects on machine volume, staff time, and workforce predictions. RESULTS: The per-case marginal reduction in technical revenue was $1,777, $4,297, $9,041, and $9,498 for palliative and breast, prostate, and lung cancer cases, respectively. The physician reduction per case in RVUs was 5.22, 10.44, 43.02, and 43.02 respectively. A department could anticipate an annual reduction in technical revenue of $540,661 and a reduction in workflow of approximately five patients or 1 to 1.5 hours per day from a hypofractionation rate of 40%. CONCLUSION: The move to hypofractionation in the United States will lead to increased pressures on departments to address budget shortfalls resulting from the decrease in per-patient revenue. This may be done through a combination of an increase in patient volume, recognition of the increased skill sets required to deliver hypofractionated radiotherapy, delay in capital purchases, and/or reduction in staff. In a value-based environment, these evolutions should improve the value proposition of radiation oncology over a fee for-service model. PMID- 27006360 TI - Time-Driven Activity-Based Costing: A Comparative Cost Analysis of Whole-Breast Radiotherapy Versus Balloon-Based Brachytherapy in the Management of Early-Stage Breast Cancer. AB - PURPOSE: Value in health care is defined as outcomes achieved per dollar spent, and understanding cost is critical to delivering high-value care. Traditional costing methods reflect charges rather than fundamental costs to provide a service. The more rigorous method of time-driven activity-based costing was used to compare cost between whole-breast radiotherapy (WBRT) and accelerated partial breast irradiation (APBI) using balloon-based brachytherapy. MATERIALS AND METHODS: For WBRT (25 fractions with five-fraction boost) and APBI (10 fractions twice daily), process maps were created outlining each activity from consultation to post-treatment follow up. Through staff interviews, time estimates were obtained for each activity. The capacity cost rates (CCR), defined as cost per minute, were calculated for personnel, equipment, and physical space. Total cost was calculated by multiplying the time required of each resource by its CCR. This was then summed and combined with cost of consumable materials. RESULTS: The total cost for WBRT was $5,333 and comprised 56% personnel costs and 44% space/equipment costs. For APBI, the total cost was $6,941 (30% higher than WBRT) and comprised 51% personnel costs, 6% space/equipment costs, and 43% consumable materials costs. The attending physician had the highest CCR of all personnel ($4.28/min), and APBI required 24% more attending time than WBRT. The most expensive activity for APBI was balloon placement and for WBRT was computed tomography simulation. CONCLUSION: APBI cost more than WBRT when using the dose/fractionation schemes analyzed. Future research should use time-driven activity-based costing to better understand cost with the aim of reducing expenditure and defining bundled payments. PMID- 27006361 TI - New day rising: state of the art in yeast functional genomics. PMID- 27006362 TI - Underage purchasing of alcohol from packaged liquor outlets: an Australian study. AB - Access to the supply of alcohol is an important factor influencing adolescent alcohol consumption. Although alcohol sales outlets are prohibited from selling alcohol to underage youth, there has been limited research investigating compliance. The present study sought to estimate the extent to which adolescents that appeared underage were successfully able to purchase alcohol from packaged liquor outlets in Australia; and to identify store and sales characteristics associated with illegal purchasing. In 2012, purchase surveys were conducted (n= 310) at packaged liquor outlets in 28 urban and rural communities across three states of Australia: Western Australia, Queensland and Victoria. Confederates successfully purchased alcohol at 60% (95% CI: 55-66) of outlets. The density of general alcohol outlets in the surrounding area and the type of liquor outlet were predictors of successful alcohol purchases; however, this was moderated by the state in which the purchase was made. Regional geographical location was also found to predict underage alcohol purchase. The majority of alcohol sales outlets in Australia breach regulations prohibiting sales to underage youth. Consistent enforcement of policies across the states of Australia, and reducing the number of alcohol outlets, will help prevent alcohol outlets illegally selling alcohol to underage adolescents. PMID- 27006363 TI - Exploring and revitalizing Indigenous food networks in Saskatchewan, Canada, as a way to improve food security. AB - The project discussed in this paper was designed to expand research and instigate revitalization of Indigenous food networks in Saskatchewan, Canada, by exploring the current state of local Indigenous food networks, creating a Facebook page, organizing volunteer opportunities and surveying workshop participants regarding their knowledge and interest in Indigenous foods. The survey included Likert scale questions and qualitative questions. Project activities and survey results are discussed using statistical and qualitative analysis of the themes. Results indicate that participants are very interested in learning more about, and having greater access to, traditional foods and suggest that supporting Indigenous food networks may be an appropriate response to food insecurity in communities. Elders and community members are vital players in Indigenous foods exploration and revitalization in Saskatchewan by passing on traditional education. PMID- 27006364 TI - Intersectoriality in Danish municipalities: corrupting the social determinants of health? AB - Action on the social determinants of health (SDH) through intersectoral policymaking is often suggested to promote health and health equity. This paper argues that the process of intersectoral policymaking influences how the SDH are construed and acted upon in municipal policymaking. We discuss how the intersectoral policy process legitimates certain practices in the setting of Danish municipal health promotion and the potential impact this can have for long term, sustainable healthy public policy. Based on ethnographic fieldwork, we show how the intention of intersectoriality produces a strong concern for integrating health into non-health sectors to ensure productive collaboration. To encourage this integration, health is often framed as a means to achieve the objectives of non-health sectors. In doing so, the intersectoral policy process tends to favor smaller-scale interventions that aim to introduce healthier practices into various settings, e.g. creating healthy school environments for increased physical activity and healthy eating. While other more overarching interventions on the health impacts of broader welfare policies (e.g. education policy) tend to be neglected. The interventions hereby neglect to address more fundamental SDH. Based on these findings, we argue that intersectoral policymaking to address the SDH may translate into a limited approach to action on so-called 'intermediary determinants' of health, and as such may end up corrupting the broader SDH. Further, we discuss how this corruption affects the intended role of non-health sectors in tackling the SDH, as it may impede the overall success and long-term sustainability of intersectoral efforts. PMID- 27006365 TI - Factors influencing workplace health promotion intervention: a qualitative systematic review. AB - Although workplace health promotion (WHP) has evolved over the last 40 years, systematically collected knowledge on factors influencing the functioning of WHP is scarce. Therefore, a qualitative systematic literature review was carried out to systematically identify and synthesize factors influencing the phases of WHP interventions: needs assessment, planning, implementation and evaluation. Research evidence was identified by searching electronic databases (Scopus, PubMed, Social Sciences Citation Index, ASSIA, ERIC, IBBS and PsycINFO) from 1998 to 2013, as well as by cross-checking reference lists of included peer-reviewed articles. The inclusion criteria were: original empirical research, description of WHP, description of barriers to and/or facilitators of the planning, implementation and/or evaluation of WHP. Finally, 54 full texts were included. From these, influencing factors were extracted and summarized using thematic analysis. The majority of influencing factors referred to the implementation phase, few dealt with planning and/or evaluation and none with needs assessment. The influencing factors were condensed into topics with respect to factors at contextual level (e.g. economic crisis); factors at organizational level (e.g. management support); factors at intervention level (e.g. quality of intervention concept); factors at implementer level (e.g. resources); factors at participant level (e.g. commitment to intervention) and factors referring to methodological and data aspects (e.g. data-collection issues). Factors regarding contextual issues and organizational aspects were identified across three phases. Therefore, future research and practice should consider not only the influencing factors at different levels, but also at different phases of WHP interventions. PMID- 27006366 TI - Libraries as 'everyday' settings: the Glasgow MCISS project. AB - A settings-based approach is now well-established in health promotion, initially undertaken in conventional places like schools and workplaces, but more recently being expressed in a wider range of what Torp et al. call 'everyday' settings. In this context, libraries have emerged as another potential setting whose ubiquity and accessibility suggests that they may be particularly effective in addressing health inequalities. Drawing on a case study-the Glasgow Macmillan Cancer Information and Support Services Library project-this paper reports on the potential for seeing 'libraries as settings' and in the context of a set of associated theoretical resources, specifically scrutinizes the nature of initiative implementation. Data were drawn from multiple sources: semi-structured interviews and focus groups with strategic partners and stakeholders, operational staff, project volunteers, service users and members of the general public. Qualitative data were complemented by quantitative insights from surveys with members of the partnership, libraries staff and volunteers. Despite some concerns associated with potentially hostile cultural and financial contexts that might threaten longer term sustainability, insights suggested that in pragmatic terms, the project was attracting sizable 'footfall' and successfully addressing a range of needs. Additionally, the formal implementation processes associated with project implementation were considered to have been highly successful in embedding the model into the library culture. In summary, there is evidence that libraries have the potential to be considered as supportive settings and could act as a model for an emergent vision of what libraries do. PMID- 27006367 TI - Awareness of nutrition problems among Vietnamese health and education professionals. AB - Professionals who provide nutrition education and consulting to the public are encouraged to take into account the health, environmental and social contexts that influence health-related attitudes and behaviours in the population. This paper examined the awareness of shifts in population health outcomes associated with the nutrition transition in Vietnam among university nutrition lecturers, health professionals and school education professionals. Most of these professionals held accurate views of the current population health issues in Vietnam. However, they differed in their awareness of the seriousness of overweight and obesity. Although the majority indicated that the prevalence of obesity and non-communicable diseases (NCDs) had increased, nearly half believed that the government should complete its attempts to control undernutrition before trying to control obesity. More health professionals believed that food marketing was responsible for the growing prevalence of children's obesity, and more of them disapproved of the marketing of less healthy food to children. In contrast, the university nutrition lecturers were least aware of food marketing and the seriousness of obesity. Of the three groups, the university nutrition lecturers held less accurate perceptions of nutrition transition problems and their likely drivers. There is an urgent need for greater provision of public nutrition education for all three groups of professionals. PMID- 27006368 TI - Political rhetoric from Canada can inform healthy public policy argumentation. AB - Household food insecurity (HFI), insufficient income to obtain adequate food, is a growing problem in Canada and other Organisation of economic cooperation and development (OECD) countries. Government political orientations impact health policies and outcomes. We critically examined Canadian political rhetoric around HFI from 1995 to 2012 as a means to support effective healthy public policy argumentation. We analysed a data set comprised of Hansard extracts on HFI from the legislative debates of the Canadian federal and three provincial governments, using thematic coding guided by interpretivist theories of policy. Extracts were examined for content, jurisdiction, the political affiliation of the legislator speaking and governing status. Members of non-governing, or 'opposition' parties, dominated the rhetoric. A central hunger-as-poverty theme was used by legislators across the political spectrum, both in government and in opposition. Legislators differed in terms of policy approach around how income should flow to citizens facing HFI: income intervention on the left, pragmatism in the centre, reliance on markets on the right. This analysis is a case-example from Canada and caution must be exercised in terms of the generalizability of findings across jurisdictions. Despite this limitation, our findings can help healthy public policy advocates in designing and communicating HFI policy interventions in OECD countries with a similar left-right spectrum. First, even with a divisive health policy issue such as actions to address HFI, core themes around poverty are widely understood. Secondly, the non-polarizing centrist, pragmatist, approach may be strategically valuable. Thirdly, it is important to treat the rhetoric of opposition members differently from that of government members. PMID- 27006369 TI - Expanding the Genetic Profile of BCC. AB - Basal cell carcinoma, the most common form of skin cancer, most often occurs as a result of aberrant Hedgehog signaling. However, new research suggests that additional molecular drivers may be involved, including mutations that lead to N Myc accumulation and oncogenic YAP1 activity. PMID- 27006370 TI - Non-invasive imaging for prediction of ventricular arrhythmias. PMID- 27006371 TI - Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome. AB - BACKGROUND: Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of (68)Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. MATERIALS AND METHODS: Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and (68)Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and (68)Ga-DOTANOC PET/CT was compared. RESULTS: Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). (68)Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). CONCLUSION: CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. (68)Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions. PMID- 27006372 TI - Psychological aptitude evaluation of the special forces candidate. AB - INTRODUCTION: Changes in recruitment procedures reduced early dismissal rates from Swiss military basic recruitment schools; however, such improvements were not reflected in premature discharge rates from the special forces (SF) (Grenadier) recruitment school. METHOD: A six-item questionnaire designed to identify recruits likely to be subject to premature dismissal on psychological or psychiatric grounds was developed and prospectively validated. The questionnaire was based on an analysis of medical and psychiatric/psychological records of 26 recruits dismissed from a SF recruitment school. Six items were identified that appeared to have prognostic value for early discharge. These six questions were submitted to the remaining applicants in the recruitment school by a suitably qualified psychologist or psychiatrist and effectively identified candidates who would be discharged early. Based on these results a 0-6 scale was developed and applied prospectively to subsequent Grenadier recruitment courses. RESULTS: Statistical analysis showed that 75% of candidates with the lowest scores would eventually complete the course and that no candidates with highest scores would subsequently complete the recruitment course. DISCUSSION: Prospective studies in subsequent recruitment courses candidates with high scores were classified as not qualified to enter the course, and those with intermediate scores were subject to additional in-depth interviews with a psychologist or psychiatrist to determine their suitability. In the following courses a correlation was established between the questionnaire score and week of discharge for those discharged. Application of this method during subsequent recruitment courses has reduced early dismissal from Swiss SF recruitment schools. PMID- 27006373 TI - Tuberculosis in Scottish military veterans: evidence from a retrospective cohort study of 57 000 veterans and 173 000 matched non-veterans. AB - OBJECTIVE: Tuberculosis was a major cause of morbidity and manpower loss in the Armed Forces during World War II. Military control programmes commenced in the 1950s but were initially limited in scope by the many recruits who were already tuberculin positive on enlistment. The aim of our study was to examine whether veterans have an increased risk of tuberculosis compared with non-veterans. METHODS: Retrospective cohort study of 57 000 veterans born 1945-1985, and 173 000 people with no record of military service, resident in Scotland, matched for age, sex and area of residence, using Cox proportional hazard analysis to compare the risk of tuberculosis overall, by birth cohort, length of service and year of diagnosis and to examine comorbidities. RESULTS: Over mean 29 years follow-up, 69 (0.12%) veterans were recorded as having tuberculosis, compared with 267 (0.15%) non-veterans (unadjusted HR 0.90, 95% CIs 0.69 to 1.19, p=0.463). Only the 1945 1949 veterans' birth cohort was at higher risk, unadjusted HR 1.54, 95% CIs 0.98 to 2.45, p=0.061, although the difference in risk did not achieve significance. Veterans born from 1950 were at significantly reduced risk of tuberculosis compared with non-veterans after adjusting for deprivation, HR 0.67, 95% CI 0.47 to 0.95, p=0.026. The most common comorbidities were smoking-related and alcohol related disease. The risk of comorbid hepatitis B or C was very low, in both veterans and non-veterans. No length of service was associated with an increased risk of tuberculosis in comparison with non-veterans. CONCLUSIONS: Scottish veterans born before 1950 are at moderately increased risk of tuberculosis compared with age, sex and geographically matched civilians with no record of service, although the difference is not statistically significant. Scottish veterans born from 1950 show a reduction in risk compared with civilians. Tuberculosis should be considered in the differential diagnosis of respiratory disease in the older veteran. PMID- 27006374 TI - Multiple testing procedures for adaptive enrichment designs: combining group sequential and reallocation approaches. AB - Adaptive enrichment designs involve preplanned rules for modifying enrollment criteria based on accrued data in an ongoing trial. For example, enrollment of a subpopulation where there is sufficient evidence of treatment efficacy, futility, or harm could be stopped, while enrollment for the remaining subpopulations is continued. We propose a new class of multiple testing procedures tailored to adaptive enrichment designs. The procedures synthesize ideas from two general approaches. As in the modified group sequential approach, the procedures gain power by leveraging the covariance among statistics for different stages and different hypotheses. As in the alpha reallocation approach, the procedures lower rejection thresholds for the remaining null hypotheses after others have been rejected. The proposed procedures are proved to have power greater than or equal to several existing methods, and to strongly control the familywise Type I error rate when statistics are normally distributed. The methods are illustrated through simulations of a trial for a surgical intervention for stroke, involving two subpopulations. PMID- 27006375 TI - Estimation of a partially linear additive model for data from an outcome dependent sampling design with a continuous outcome. AB - Outcome-dependent sampling (ODS) designs have been well recognized as a cost effective way to enhance study efficiency in both statistical literature and biomedical and epidemiologic studies. A partially linear additive model (PLAM) is widely applied in real problems because it allows for a flexible specification of the dependence of the response on some covariates in a linear fashion and other covariates in a nonlinear non-parametric fashion. Motivated by an epidemiological study investigating the effect of prenatal polychlorinated biphenyls exposure on children's intelligence quotient (IQ) at age 7 years, we propose a PLAM in this article to investigate a more flexible non-parametric inference on the relationships among the response and covariates under the ODS scheme. We propose the estimation method and establish the asymptotic properties of the proposed estimator. Simulation studies are conducted to show the improved efficiency of the proposed ODS estimator for PLAM compared with that from a traditional simple random sampling design with the same sample size. The data of the above-mentioned study is analyzed to illustrate the proposed method. PMID- 27006376 TI - Estimating the number of foreign women with female genital mutilation/cutting in Italy. AB - BACKGROUND: Female genital mutilation/cutting (FGM/C), is an emerging topic in Europe as a consequence of the increasing proportion of women migrating from Africa. The prevalence of FGM/C is however unknown in Europe, as there are no country-representative surveys on this topic. The aim of this study is to provide an estimate for Italy for the year 2010. METHODS: This study relies on the results of the First Survey on Women at Risk of FGM/C held in Italy in 2010. This cross-sectional survey involved 1000 migrants from the main FGM/C practicing countries aged 15-49 living in the Italian region of Lombardy. The estimate presented is based on a method combining direct estimates for the communities involved in the survey and indirect estimates for other communities. Indirect estimations were obtained using a refinement of the most general extrapolation-of country-prevalence-data method. RESULTS: It is estimated that some 57 000 foreign girls and women aged 15-49 with FGM/C were living in Italy in 2010. The Nigerian community is the most affected, with around 20 000 women with FGM/C (35.5% of the total number women affected in Italy), followed by the Egyptian community (around 18 600 women with FGM/C; 32.5%). Another 15% of the women affected are from the Horn of Africa, notably from Ethiopia (3200 women; 5.5%), Eritrea (2800 women; 4.9%) and Somalia (2300 women; 4%). CONCLUSIONS: This study offers an additional methodological advancement by proposing a combination of direct and indirect estimation of FGM/C. The results are crucial information to plan interventions and targeted policies. PMID- 27006378 TI - Early Events in the Molecular Pathogenesis of Lung Cancer. AB - The majority of cancer-related deaths in the United States and worldwide are attributed to lung cancer. There are more than 90 million smokers in the United States who represent a significant population at elevated risk for lung malignancy. In other epithelial tumors, it has been shown that if neoplastic lesions can be detected and treated at their intraepithelial stage, patient prognosis is significantly improved. Thus, new strategies to detect and treat lung preinvasive lesions are urgently needed in order to decrease the overwhelming public health burden of lung cancer. Limiting these advances is a poor knowledge of the earliest events that underlie lung cancer development and that would constitute markers and targets for early detection and prevention. This review summarizes the state of knowledge of human lung cancer pathogenesis and the molecular pathology of premalignant lung lesions, with a focus on the molecular premalignant field that associates with lung cancer development. Lastly, we highlight new approaches and models to study genome-wide alterations in human lung premalignancy in order to facilitate the discovery of new markers for early detection and prevention of this fatal disease. Cancer Prev Res; 9(7); 518-27. (c)2016 AACR. PMID- 27006377 TI - Soy Protein Isolate Protects Against Ethanol-Mediated Tumor Progression in Diethylnitrosamine-Treated Male Mice. AB - In this study, diethylnitrosamine-treated male mice were assigned to three groups: (i) a 35% high fat ethanol liquid diet (EtOH) with casein as the protein source, (ii) the same EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/SPI), (iii) and a chow group. EtOH feeding continued for 16 weeks. As expected, EtOH increased the incidence and multiplicity of basophilic lesions and adenomas compared with the chow group, P < 0.05. Soy protein replacement of casein in the EtOH diet significantly reduced adenoma progression when compared with the EtOH and EtOH/SPI group (P < 0.05). Tumor reduction in the EtOH/SPI group corresponded to reduced liver injury associated with decreased hepatic Tnfalpha and Cd14 antigen (Cd14) expression and decreased nuclear accumulation of NF-kappaB1 protein compared with the EtOH group (P < 0.05). Detection of sphingolipids using high-resolution matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging mass spectrometry revealed increased accumulation of long acyl chain ceramide species, and sphingosine-1-phosphate (S1P) in the EtOH group that were significantly reduced in the EtOH/SPI group. Chronic EtOH feeding also increased mRNA expression of beta-catenin transcriptional targets, including cyclin D1 (Ccnd1), matrix metallopeptidase 7 (Mmp7), and glutamine synthetase (Glns), which were reduced in the EtOH/SPI group (P < 0.05). We conclude that soy prevents tumorigenesis by reducing proinflammatory and oxidative environment resulting from EtOH-induced hepatic injury, and by reducing hepatocyte proliferation through inhibition of beta-catenin signaling. These mechanisms may involve changes in sphingolipid signaling. Cancer Prev Res; 9(6); 466-75. (c)2016 AACR. PMID- 27006379 TI - Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques. AB - Endogenous estrogens influence mammary gland development during puberty and breast cancer risk during adulthood. Early-life exposure to dietary or environmental estrogens may alter estrogen-mediated processes. Soy foods contain phytoestrogenic isoflavones (IF), which have mixed estrogen agonist/antagonist properties. Here, we evaluated mammary gland responses over time in pubertal female cynomolgus macaques fed diets containing either casein/lactalbumin (n = 12) or soy protein containing a human-equivalent dose of 120 mg IF/day (n = 17) for approximately 4.5 years spanning menarche. We assessed estrogen receptor (ER) expression and activity, promoter methylation of ERs and their downstream targets, and markers of estrogen metabolism. Expression of ERalpha and classical ERalpha response genes (TFF1, PGR, and GREB1) decreased with maturity, independent of diet. A significant inverse correlation was observed between TFF1 mRNA and methylation of CpG sites within the TFF1 promoter. Soy effects included lower ERbeta expression before menarche and lower mRNA for ERalpha and GREB1 after menarche. Expression of GATA-3, an epithelial differentiation marker that regulates ERalpha-mediated transcription, was elevated before menarche and decreased after menarche in soy-fed animals. Soy did not significantly alter expression of other ER activity markers, estrogen-metabolizing enzymes, or promoter methylation for ERs or ER-regulated genes. Our results demonstrate greater ER expression and activity during the pubertal transition, supporting the idea that this life stage is a critical window for phenotypic modulation by estrogenic compounds. Pubertal soy exposure decreases mammary ERalpha expression after menarche and exerts subtle effects on receptor activity and mammary gland differentiation. Cancer Prev Res; 9(5); 385-95. (c)2016 AACR. PMID- 27006380 TI - Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules? AB - In hypofractionated stereotactic radiotherapy (SRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared with conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to hypofractionated SRT is the mathematical model for dose evaluation and conversion. The linear quadratic (LQ) model and biologically effective dose (BED) have been suggested to be incorrect when used for hypofractionation. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo, since it does not take reoxygenation into account. Correction of the errors, estimated at 5-20%, associated with the use of BED is necessary when it is used for SRT. High fractional doses have been reported to exhibit effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. This may be an interesting topic that should be further investigated. Radioresistance of hypoxic tumor cells is more problematic in hypofractionated SRT, so trials of hypoxia-targeted agents are encouraged in the future. In this review, the radiobiological characteristics of hypofractionated SRT are summarized, and based on the considerations, we would like to recommend 60 Gy in eight fractions delivered three times a week for lung tumors larger than 2 cm in diameter. PMID- 27006381 TI - Protective effects of rosmarinic acid against radiation-induced damage to the hematopoietic system in mice. AB - Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid. It is a potent antioxidant that functions by scavenging free radicals. Here, we used a 30-day survival assay to investigate the radioprotective effects of RA. Mice were treated with RA once per day for 10 consecutive days starting at 3 days before gamma irradiation at 7.5 Gy until 7 days post irradiation. Mice treated with 100 and 200 mg/kg body weight (bw) of RA had 30-day survival rates of 89% and 72%, respectively, compared with 32% in the control group, and the differences were statistically significant (P = 0.0008 and 0.0421, respectively). Spleen colony-forming units (CFU-S), the number of nucleated cells in the bone marrow (BMNC), bone marrow DNA content, and hematological parameters of the peripheral blood were measured to investigate the radioprotective effect of RA on the hematopoietic system. The treatment groups that received RA at 50, 100 and 150 mg/kg bw and whole-body exposure to 5.5 Gy of (137)Cs gamma- radiation had significantly higher CFU-S, BMNC and DNA content than the irradiation-only group. Assessment of hematological parameters in the peripheral blood showed that the treatment groups receiving RA at doses of 50, 100 and 150 mg/kg bw had higher white blood cell counts, hemoglobin and platelets than the radiation-only group. These results suggested that the administration of RA promoted the recovery of peripheral blood cells in irradiated mice. PMID- 27006382 TI - Gene expression profiling in undifferentiated thyroid carcinoma induced by high dose radiation. AB - Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose gamma-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range. PMID- 27006383 TI - Sexpression:UK. PMID- 27006384 TI - Gendered Intelligence. PMID- 27006385 TI - Overdose of oral contraceptive pills as a means of intentional self-poisoning amongst young women in Sri Lanka: considerations for family planning. AB - OBJECTIVE: Oral contraceptive pills (OCPs) are one of the most popular family planning methods in Sri Lanka. As part of two hospital-based studies on self harm, the use of OCPs was identified, from yet unpublished results, as a means of intentional self-poisoning. To inform future guidelines for better OCP promotion, this article aims to describe the extent, patient characteristics and outcomes of OCP self-poisoning in the North Central Province of Sri Lanka. METHODS: A secondary analysis was carried out on two hospital-based self-harm case series, from January 2011 to June 2014. RESULTS: Fifty-four patients (52 women and two men) with an overdose of OCP as a means of intentional self-poisoning were admitted to one of the surveyed hospitals. The median age of the patients was 19 (interquartile range, 5) years. None of the patients were severely sick from their overdose and two-thirds of the patients were discharged within a day of admission. Intentional self-poisoning with OCPs represented less than 5% of all types of intentional medicine self-poisonings recorded at the hospitals. Information available for a subset of female patients indicates that many cases (13/23, 56.5%) were in their first year of marriage. CONCLUSIONS: More research is required to understand why young women in rural Sri Lanka overdose with OCPs as a means of intentional self-poisoning. Although the toxicity of OCPs is low and the public health significance of OCP poisoning remains minor, reproductive health service providers should be attentive to OCP overdose, monitor the development of this problem, and ensure appropriate information to OCP users. PMID- 27006386 TI - Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. AB - Clonal cytogenetic evolution with additional chromosomal abnormalities (ACAs) in chronic myelogenous leukemia (CML) is generally associated with decreased response to tyrosine kinase inhibitor (TKI) therapy and adverse survival. Although ACAs are considered as a sign of disease progression and have been used as one of the criteria for accelerated phase, the differential prognostic impact of individual ACAs in CML is unknown, and a classification system to reflect such prognostic impact is lacking. In this study, we aimed to address these questions using a large cohort of CML patients treated in the era of TKIs. We focused on cases with single chromosomal changes at the time of ACA emergence and stratified the 6 most common ACAs into 2 groups: group 1 with a relatively good prognosis including trisomy 8, -Y, and an extra copy of Philadelphia chromosome; and group 2 with a relatively poor prognosis including i(17)(q10), -7/del7q, and 3q26.2 rearrangements. Patients in group 1 showed much better treatment response and survival than patients in group 2. When compared with cases with no ACAs, ACAs in group 2 conferred a worse survival irrelevant to the emergence phase and time. In contrast, ACAs in group 1 had no adverse impact on survival when they emerged from chronic phase or at the time of CML diagnosis. The concurrent presence of 2 or more ACAs conferred an inferior survival and can be categorized into the poor prognostic group. PMID- 27006388 TI - MIP-1alpha/CCL3-expressing basophil-lineage cells drive the leukemic hematopoiesis of chronic myeloid leukemia in mice. AB - Basophilia is a frequently observed hematological abnormality in chronic myeloid leukemia (CML), but its pathophysiological roles are undefined. We previously demonstrated that an inflammatory chemokine, CCL3, preferentially acts on normal hematopoietic stem/progenitor cells and crucially contributes to the maintenance of leukemia initiating cells (LICs) in bone marrow (BM) during the initiation process of CML. However, the major cellular source of CCL3 in BM and the precise mechanism of CCL3-mediated maintenance of LICs remain to be investigated. To delineate the cellular process facilitating this CCL3-mediated crosstalk between normal and leukemic hematopoiesis, we precisely examined CCL3-expressing cells and their functions in both normal hematopoiesis and CML leukemogenesis. Herein, we demonstrate that basophils can constitutively express CCL3 to negatively regulate the normal hematopoietic process, especially hematopoietic reconstitution after BM transplantation. Moreover, CCL3-expressing basophil-like leukemia cells were found to accumulate in CML BM and supported the predominant expansion of LICs therein. These observations suggest that intra-BM basophil expansion can favor leukemia-tropic hematopoiesis in CML by providing CCL3, a potent inhibitor of normal hematopoiesis and that basophil-derived CCL3 may be a novel target molecule for the treatment of CML. PMID- 27006387 TI - A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain. AB - Factor XI (FXI) is the zymogen of FXIa, which cleaves FIX in the intrinsic pathway of coagulation. FXI is known to exist as a dimer and interacts with multiple proteins via its 4 apple domains in the "saucer section" of the enzyme; however, to date, no complex crystal structure has been described. To investigate protein interactions of FXI, a large random peptide library consisting of 10(6) to 10(7) peptides was screened for FXI binding, which identified a series of FXI binding motifs containing the signature Asp-Phe-Pro (DFP) tripeptide. Motifs containing this core tripeptide were found in diverse proteins, including the known ligand high-molecular-weight kininogen (HK), as well as the extracellular matrix proteins laminin and collagen V. To define the binding site on FXI, we determined the crystal structure of FXI in complex with the HK-derived peptide NPISDFPDT. This revealed the location of the DFP peptide bound to the FXI apple 2 domain, and central to the interaction, the DFP phenylalanine side-chain inserts into a major hydrophobic pocket in the apple 2 domain and the isoleucine occupies a flanking minor pocket. Two further structures of FXI in complex with the laminin-derived peptide EFPDFP and a DFP peptide from the random screen demonstrated binding in the same pocket, although in a slightly different conformation, thus revealing some flexibility in the molecular interactions of the FXI apple 2 domain. PMID- 27006390 TI - Disturbed sialic acid recognition on endothelial cells and platelets in complement attack causes atypical hemolytic uremic syndrome. AB - Uncontrolled activation of the complement system against endothelial and blood cells is central to the pathogenesis of atypical hemolytic uremic syndrome (aHUS). aHUS patients frequently carry mutations in the inhibitory complement regulator factor H (FH). Mutations cluster in domains 19 and 20 (FH19-20), which are critical for recognizing self surfaces. On endothelial cells, binding of FH is generally attributed to heparan sulfate. This theory, however, is questioned by the puzzling observation that some aHUS-associated mutations markedly enhance FH binding to heparin and endothelial cells. In this article, we show that, instead of disturbed heparin interactions, the impaired ability of C-terminal mutant FH molecules to recognize sialic acid in the context of surface-bound C3b explains their pathogenicity. By using recombinant FH19-20 as a competitor for FH and measuring erythrocyte lysis and deposition of complement C3b and C5b-9 on endothelial cells and platelets, we now show that several aHUS-associated mutations, which have been predicted to impair FH19-20 binding to sialic acid, prevent FH19-20 from antagonizing FH function on cells. When sialic acid was removed, the wild-type FH19-20 also lost its ability to interfere with FH function on cells. These results indicate that sialic acid is critical for FH mediated complement regulation on erythrocytes, endothelial cells, and platelets. The inability of C-terminal mutant FH molecules to simultaneously bind sialic acid and C3b on cells provides a unifying explanation for their association with aHUS. Proper formation of FH-sialic acid-C3b complexes on surfaces exposed to plasma is essential for preventing cell damage and thrombogenesis characteristic of aHUS. PMID- 27006389 TI - Mutations in succinate dehydrogenase B (SDHB) enhance neutrophil survival independent of HIF-1alpha expression. PMID- 27006392 TI - Examining Clinical Utility of Imaging for Inpatient Palliative Care. AB - BACKGROUND: Medicine in the final months of life is increasingly interventional, both in the manner by which life may be prolonged and symptoms may be reduced. Radiology is frequently utilized to provide diagnostic clarity and improve symptom control. As with any intervention, examining the benefit and potential harms of a procedure is required to establish its role in ongoing clinical care. METHODS: This retrospective cohort study involved patients admitted to an inpatient palliative care unit between October 2013 and September 2014. Data were collected using clinical databases manually searched by the researchers. RESULTS: Of 388 admissions, there were a total of 154 imaging events completed in 85 patients. Patients who had imaging performed had longer mean length of stays, more likely to be discharged home, and male. Very few imaging events (4%) occurred in the 3 days prior to death and none on the day of death. In total, 43% of imaging confirmed the clinical suspicion and management changed 42% of times. Limbs X-rays and computed tomography brain had low rates of confirming clinical suspicion (21% and 17%) and changing management (21% and 33%). There were a total of 7 complications resulting from imaging, the majority due to interventional procedures. CONCLUSION: The use of imaging in inpatient palliative care seems to be of substantive utility, prompting alterations in management in >40% of instances. The majority of imaging occurred prior to the terminal phase of the disease and with few complications. PMID- 27006391 TI - Pain Intensity and Misconceptions Among Hospice Patients With Cancer and Their Caregivers: Status After 2 Decades. AB - There is little evidence about barriers to pain management or their relationships with pain outcomes of hospice patients with cancer. The purpose of the study was to determine the barriers reported by hospice patients with cancer and their caregivers and the relationships with demographic characteristics and the patients' pain. In this cross-sectional study, we used selected baseline data from an ongoing randomized clinical trial of patient and lay caregiver dyads receiving home-level hospice care. Participants used an Internet-enabled tablet to complete the valid, reliable measures of pain intensity, pain management barriers (Barriers Questionnaire 13 items [BQ-13]), and demographic characteristics. The responses indicate that the 2 areas of highest concern (mean scores >3) to both patients and caregivers were "pain means disease progression" and "constipation." Additionally, 3 other areas of highest concern (mean scores >3) to caregivers were "addiction" pain medicine causing "one to do embarrassing things" and "confusion." The mean BQ-13 scores ranged from 0.2 to 4.9 and averaged 2.6 +/- 0.9 for the patients and ranged from 0.5 to 4.7 and averaged 2.7 +/- 0.9 for the caregivers. Mean barrier scores remain high and were not different between patients and their caregivers or significantly related to the patients' pain intensity. However, there were differences in race, ethnic, and hospice setting in the barrier scores. Patients with Hispanic heritage reported higher barrier scores than non-Hispanic patients. Together, these findings not only support prior research findings but also contribute new insights about pain intensity and pain barriers that are relevant to hospices serving minorities with cancer. PMID- 27006393 TI - NHS England rolls out world's first national diabetes prevention programme. PMID- 27006394 TI - Structure of an alpha-Helical Peptide and Lipopeptide Bound to the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule CD1d. AB - Mouse CD1d is a nonclassical MHC molecule able to present lipids and glycolipids to a specialized subset of T cells known as natural killer T cells. The antigens presented by CD1d have been shown to cover a broad range of chemical structures and to follow precise rules determining the potency of the antigen in the context of T cell activation. Together with lipids, initial reports suggested that CD1d can also bind and present hydrophobic peptides with (F/W)XX(I/L/M)XXW. However, the exact location of peptide binding and the molecular basis for the required motif are currently unknown. Here we present the crystal structure of the first peptide identified to bind CD1d, p99, and show that it binds in the antigen binding groove of CD1d in a manner compatible with its presentation to T cell receptors. Interestingly, the peptide adopts an alpha-helical conformation, which orients the motif residues toward its deep binding groove, therefore explaining the molecular requirements for peptide binding. Moreover, we demonstrate that a lipopeptide version of the same peptide is able to bind CD1d in a similar conformation, identifying another class of molecules binding this antigen presenting molecule. PMID- 27006395 TI - Brain-derived Neurotrophic Factor in Megakaryocytes. AB - The biosynthesis of endogenous brain-derived neurotrophic factor (BDNF) has thus far been examined in neurons where it is expressed at very low levels, in an activity-dependent fashion. In humans, BDNF has long been known to accumulate in circulating platelets, at levels far higher than in the brain. During the process of blood coagulation, BDNF is released from platelets, which has led to its extensive use as a readily accessible biomarker, under the assumption that serum levels may somehow reflect brain levels. To identify the cellular origin of BDNF in platelets, we established primary cultures of megakaryocytes, the progenitors of platelets, and we found that human and rat megakaryocytes express the BDNF gene. Surprisingly, the pattern of mRNA transcripts is similar to neurons. In the presence of thapsigargin and external calcium, the levels of the mRNA species leading to efficient BDNF translation rapidly increase. Under these conditions, pro-BDNF, the obligatory precursor of biologically active BDNF, becomes readily detectable. Megakaryocytes store BDNF in alpha-granules, with more than 80% of them also containing platelet factor 4. By contrast, BDNF is undetectable in mouse megakaryocytes, in line with the absence of BDNF in mouse serum. These findings suggest that alterations of BDNF levels in human serum as reported in studies dealing with depression or physical exercise may primarily reflect changes occurring in megakaryocytes and platelets, including the ability of the latter to retain and release BDNF. PMID- 27006396 TI - Hydrogen/Deuterium Exchange Kinetics Demonstrate Long Range Allosteric Effects of Thumb Site 2 Inhibitors of Hepatitis C Viral RNA-dependent RNA Polymerase. AB - New nonnucleoside analogs are being developed as part of a multi-drug regimen to treat hepatitis C viral infections. Particularly promising are inhibitors that bind to the surface of the thumb domain of the viral RNA-dependent RNA polymerase (NS5B). Numerous crystal structures have been solved showing small molecule non nucleoside inhibitors bound to the hepatitis C viral polymerase, but these structures alone do not define the mechanism of inhibition. Our prior kinetic analysis showed that nonnucleoside inhibitors binding to thumb site-2 (NNI2) do not block initiation or elongation of RNA synthesis; rather, they block the transition from the initiation to elongation, which is thought to proceed with significant structural rearrangement of the enzyme-RNA complex. Here we have mapped the effect of three NNI2 inhibitors on the conformational dynamics of the enzyme using hydrogen/deuterium exchange kinetics. All three inhibitors rigidify an extensive allosteric network extending >40 A from the binding site, thus providing a structural rationale for the observed disruption of the transition from distributive initiation to processive elongation. The two more potent inhibitors also suppress slow cooperative unfolding in the fingers extension thumb interface and primer grip, which may contribute their stronger inhibition. These results establish that NNI2 inhibitors act through long range allosteric effects, reveal important conformational changes underlying normal polymerase function, and point the way to the design of more effective allosteric inhibitors that exploit this new information. PMID- 27006398 TI - Crystal Structure of Mycobacterium tuberculosis H37Rv AldR (Rv2779c), a Regulator of the ald Gene: DNA BINDING AND IDENTIFICATION OF SMALL MOLECULE INHIBITORS. AB - Here we report the crystal structure of M. tuberculosis AldR (Rv2779c) showing that the N-terminal DNA-binding domains are swapped, forming a dimer, and four dimers are assembled into an octamer through crystal symmetry. The C-terminal domain is involved in oligomeric interactions that stabilize the oligomer, and it contains the effector-binding sites. The latter sites are 30-60% larger compared with homologs like MtbFFRP (Rv3291c) and can consequently accommodate larger molecules. MtbAldR binds to the region upstream to the ald gene that is highly up regulated in nutrient-starved tuberculosis models and codes for l-alanine dehydrogenase (MtbAld; Rv2780). Further, the MtbAldR-DNA complex is inhibited upon binding of Ala, Tyr, Trp and Asp to the protein. Studies involving a ligand binding site G131T mutant show that the mutant forms a DNA complex that cannot be inhibited by adding the amino acids. Comparative studies suggest that binding of the amino acids changes the relative spatial disposition of the DNA-binding domains and thereby disrupt the protein-DNA complex. Finally, we identified small molecules, including a tetrahydroquinoline carbonitrile derivative (S010-0261), that inhibit the MtbAldR-DNA complex. The latter molecules represent the very first inhibitors of a feast/famine regulatory protein from any source and set the stage for exploring MtbAldR as a potential anti-tuberculosis target. PMID- 27006397 TI - The Gas6-Axl Protein Interaction Mediates Endothelial Uptake of Platelet Microparticles. AB - Upon activation, platelets release plasma membrane-derived microparticles (PMPs) exposing phosphatidylserine on their surface. The functions and clearance mechanism of these microparticles are incompletely understood. As they are pro coagulant and potentially pro-inflammatory, rapid clearance from the circulation is essential for prevention of thrombotic diseases. The tyrosine kinase receptors Tyro3, Axl, and Mer (TAMs) and their ligands protein S and Gas6 are involved in the uptake of phosphatidylserine-exposing apoptotic cells in macrophages and dendritic cells. Both TAMs and their ligands are expressed in the vasculature, the functional significance of which is poorly understood. In this study, we investigated how vascular TAMs and their ligands may mediate endothelial uptake of PMPs. PMPs, generated from purified human platelets, were isolated by ultracentrifugation and labeled with biotin or PKH67. The uptake of labeled microparticles in the presence of protein S and Gas6 in human aortic endothelial cells and human umbilical vein endothelial cells was monitored by flow cytometry, Western blotting, and confocal/electron microscopy. We found that both endothelial cell types can phagocytose PMPs, and by using TAM-blocking antibodies or siRNA knockdown of individual TAMs, we show that the uptake is mediated by endothelial Axl and Gas6. As circulating PMP levels were not altered in Gas6(-/-) mice compared with Gas6(+/+) mice, we hypothesize that the Gas6-mediated uptake is not a means to clear the bulk of circulating PMPs but may serve to locally phagocytose PMPs generated at sites of platelet activation and as a way to effect endothelial responses. PMID- 27006399 TI - Contextual Role of a Salt Bridge in the Phage P22 Coat Protein I-Domain. AB - The I-domain is a genetic insertion in the phage P22 coat protein that chaperones its folding and stability. Of 11 acidic residues in the I-domain, seven participate in stabilizing electrostatic interactions with basic residues across elements of secondary structure, fastening the beta-barrel fold. A hydrogen bonded salt bridge between Asp-302 and His-305 is particularly interesting as Asp 302 is the site of a temperature-sensitive-folding mutation. The pKa of His-305 is raised to 9.0, indicating the salt bridge stabilizes the I-domain by ~4 kcal/mol. Consistently, urea denaturation experiments indicate the stability of the WT I-domain decreases by 4 kcal/mol between neutral and basic pH. The mutants D302A and H305A remove the pH dependence of stability. The D302A substitution destabilizes the I-domain by 4 kcal/mol, whereas H305A had smaller effects, on the order of 1-2 kcal/mol. The destabilizing effects of D302A are perpetuated in the full-length coat protein as shown by a higher sensitivity to protease digestion, decreased procapsid assembly rates, and impaired phage production in vivo By contrast, the mutants have only minor effects on capsid expansion or stability in vitro The effects of the Asp-302-His-305 salt bridge are thus complex and context-dependent. Substitutions that abolish the salt bridge destabilize coat protein monomers and impair capsid self-assembly, but once capsids are formed the effects of the substitutions are overcome by new quaternary interactions between subunits. PMID- 27006400 TI - Persistent Chromatin Modifications Induced by High Fat Diet. AB - Obesity is a highly heritable complex disease that results from the interaction of multiple genetic and environmental factors. Formerly obese individuals are susceptible to metabolic disorders later in life, even after lifestyle changes are made to mitigate the obese state. This is reminiscent of the metabolic memory phenomenon originally observed for persistent complications in diabetic patients, despite subsequent glycemic control. Epigenetic modifications represent a potential mediator of this observed memory. We previously demonstrated that a high fat diet leads to changes in chromatin accessibility in the mouse liver. The regions of greatest chromatin changes in accessibility are largely strain dependent, indicating a genetic component in diet-induced chromatin alterations. We have now examined the persistence of diet-induced chromatin accessibility changes upon diet reversal in two strains of mice. We find that a substantial fraction of loci that undergo chromatin accessibility changes with a high fat diet remains in the remodeled state after diet reversal in C57BL/6J mice. In contrast, the vast majority of diet-induced chromatin accessibility changes in A/J mice are transient. Our data also indicate that the persistent chromatin accessibility changes observed in C57BL/6J mice are associated with specific transcription factors and histone post-translational modifications. The persistent loci identified here are likely to be contributing to the overall phenotype and are attractive targets for therapeutic intervention. PMID- 27006401 TI - FXYD5 Protein Has a Pro-inflammatory Role in Epithelial Cells. AB - The FXYD proteins are a family of small membrane proteins that share an invariant four amino acid signature motif F-X-Y-D and act as tissue-specific regulatory subunits of the Na,K-ATPase. FXYD5 (also termed dysadherin or RIC) is a structurally and functionally unique member of the FXYD family. As other FXYD proteins, FXYD5 specifically interacts with the Na,K-ATPase and alters its kinetics by increasing Vmax However, unlike other family members FXYD5 appears to have additional functions, which cannot be readily explained by modulation of transport kinetics. Knockdown of FXYD5 in MDA-MB-231 breast cancer cells largely decreases expression and secretion of the chemokine CCL2 (MCP-1). A related effect has also been observed in renal cell carcinoma cells. The current study aims to further characterize the relationship between the expression of FXYD5 and CCL2 secretion. We demonstrate that transfection of M1 epithelial cell line with FXYD5 largely increases lipopolysaccharide (LPS) stimulated CCL2 mRNA and secretion of the translated protein. We have completed a detailed analysis of the molecular events leading to the above response. Our key findings indicate that FXYD5 generates a late response by increasing the surface expression of the TNFalpha receptor, without affecting its total protein level, or mRNA transcription. LPS administration to mice demonstrates induced secretion of CCL2 and TNFalpha in FXYD5-expressing lung peripheral tissue, which suggests a possible role for FXYD5 in normal epithelia during inflammation. PMID- 27006403 TI - A review of health-related quality of life patient-reported outcome measures in cardiovascular nursing. AB - BACKGROUND: The traditional use of physically focused outcome measures fails to capture holistic, quality of life issues of importance to patients. The relatively recent, rapidly growing interest in patient-reported outcome measures (PROMs) attests to this and clinicians are faced with difficult decisions regarding their choice and use. AIMS: The purpose of this review was to identify and synthesise the literature pertaining to the concept of quality of life and the main PROMs used to measure this in the cardiovascular field. METHODS: A review of the recent literature was undertaken on commonly used cardiovascular health-related quality of life (HRQoL) PROMs. RESULTS: Two types of HRQoL PROMs are available: disease-specific and generic. Both have limitations, and in many instances there is merit in using a combination, depending on the medical condition and treatment. In addition to psychometric considerations such as reliability, validity and responsiveness, the choice of a PROM will depend on factors such as the patient/investigator burden its use may impose, resources, costs, intellectual property and copyright issues. A new 'hybrid' HRQoL PROM for use in patients across the main cardiovascular disease presentations - angina, myocardial infarction and heart failure - appears to show promise. CONCLUSIONS: Cardiovascular HRQoL PROMs have a wide variety of uses and can help clinicians, researchers, managers and policy makers in decision making and provide indicators of clinical and institutional quality and outcomes. New HRQoL PROMs are emerging and their choice and use should be determined by a host of issues, including psychometric properties, acceptability, feasibility and cost. PMID- 27006402 TI - The Unstructured N-terminal Region of Arabidopsis Group 4 Late Embryogenesis Abundant (LEA) Proteins Is Required for Folding and for Chaperone-like Activity under Water Deficit. AB - Late embryogenesis abundant (LEA) proteins are a conserved group of proteins widely distributed in the plant kingdom that participate in the tolerance to water deficit of different plant species. In silico analyses indicate that most LEA proteins are structurally disordered. The structural plasticity of these proteins opens the question of whether water deficit modulates their conformation and whether these possible changes are related to their function. In this work, we characterized the secondary structure of Arabidopsis group 4 LEA proteins. We found that they are disordered in aqueous solution, with high intrinsic potential to fold into alpha-helix. We demonstrate that complete dehydration is not required for these proteins to sample ordered structures because milder water deficit and macromolecular crowding induce high alpha-helix levels in vitro, suggesting that prevalent conditions under water deficit modulate their conformation. We also show that the N-terminal region, conserved across all group 4 LEA proteins, is necessary and sufficient for conformational transitions and that their protective function is confined to this region, suggesting that folding into alpha-helix is required for chaperone-like activity under water limitation. We propose that these proteins can exist as different conformers, favoring functional diversity, a moonlighting property arising from their structural dynamics. PMID- 27006404 TI - Uric Acid is a Useful Tool to Predict Contrast-Induced Nephropathy. AB - Developing contrast-induced nephropathy (CIN) after primary percutaneous coronary intervention (pPCI) has a negative impact on survival and morbidity. We assessed the predictive value of serum uric acid (SUA) for the development of CIN in patients with ST-segment elevation myocardial infarction (STEMI) who underwent pPCI. Contrast-induced nephropathy was defined an increase of >=25% or >=0.5 mg/dL in creatinine concentrations within 72 hours after pPCI. Patients were divided into 2 groups according to admission median SUA level. Serum uric acid level was <5.4 mg/dL (group 1; n = 222) and >=5.4 mg/dL (group 2; n = 228). Compared to group 1, development of CIN (12% vs 20%, P < .001) was significantly greater in group 2. Using a cut point of >5.45 mg/dL, the SUA level predicted development of CIN with a sensitivity of 70% and specificity of 67%. In multiple logistic regression analysis, SUA level, diabetes mellitus, left ventricular ejection fraction <50%, contrast volume, estimated glomerular filtration rate, and C-reactive protein level emerged as independent predictors of CIN. In conclusion, elevated SUA is an independent risk factor for the development of CIN after pPCI in patients with STEMI. PMID- 27006405 TI - Unsound waste management and public health: The neglected link? PMID- 27006406 TI - High rates of psychiatric diagnoses are found in young transgender women. PMID- 27006407 TI - Characteristics of Hospitalized Children With a Diagnosis of Malnutrition: United States, 2010. AB - INTRODUCTION: Malnutrition is common in hospitalized patients in the United States. In 2010, 80,710 of 6,280,710 hospitalized children <17 years old had a coded diagnosis of malnutrition (CDM). This report summarizes nationally representative, person-level characteristics of hospitalized children with a CDM. METHODS: Data are from the 2010 Healthcare Cost and Utilization Project, which contains patient-level data on hospital inpatient stays. When weighted appropriately, estimates from the project represent all U.S. hospitalizations. The data set contains up to 25 ICD-9-CM diagnostic codes for each patient. Children with a CDM listed during hospitalization were identified. RESULTS: In 2010, 1.3% of hospitalized patients <17 years had a CDM. Since the data include only those with a CDM, malnutrition's true prevalence may be underrepresented. Length of stay among children with a CDM was almost 2.5 times longer than those without a CDM. Hospital costs for children with a CDM were >3 times higher than those without a CDM. Hospitalized children with a CDM were less likely to have routine discharge and almost 3.5 times more likely to require postdischarge home care. Children with a CDM were more likely to have multiple comorbidities. CONCLUSIONS: Hospitalized children with a CDM are associated with more comorbidities, longer hospital stay, and higher healthcare costs than those without this diagnosis. These undernourished children may utilize more healthcare resources in the hospital and community. Clinicians and policymakers should factor this into healthcare resource utilization planning. Recognizing and accurately coding malnutrition in hospitalized children may reveal the true prevalence of malnutrition. PMID- 27006408 TI - Dietary omega-6/omega-3 Polyunsaturated Fatty Acid Ratios Affect the Homeostasis of Th/Treg Cells in Mice With Dextran Sulfate Sodium-Induced Colitis. AB - BACKGROUND: This study evaluated the effect of different dietary omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: There were 3 control and 3 colitis groups. Mice were fed for 24 days with diets with soybean oil (S), a mixture of soybean oil and low fish oil content (LF), or high fish oil content (HF). The ratio of omega-6/omega-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups were provided 2% DSS in drinking water during days 15-19. All mice drank distilled water from days 20-24 for recovery and were sacrificed on day 25. RESULTS: Colitis resulted in higher blood Th1, Th2, and Th17 and lower Treg percentages. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Furthermore, the percentages of blood Th1, Th2, and Th17 cells were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with an omega-6/omega-3 PUFA ratio of 2:1 had more pronounced effects than the group with a ratio of 4:1. CONCLUSIONS: Diets with an omega 6/omega-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared with the omega-6/omega-3 PUFA ratio of 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis. PMID- 27006409 TI - Inclusion of the equity focus and social determinants of health in health care education programmes in Colombia: a qualitative approach. AB - PURPOSE: The Pan American Health Organization (PAHO) and the Colombian Ministry of Health and Social Protection have determined a need for an approach to include Equity Focus (EF) and Social Determinants of Health (SDH) in health training programmes in Colombia. We studied the incorporation of EF and SDH in the curricula of several universities in Colombia to identify opportunities to strengthen their inclusion. METHODS: Qualitative methodology was performed in two stages: (i) initial exploration (self-administered questionnaires and review of curricula) and (ii) validation of the information (semi-structured interviews). RESULTS: The inclusion of the EF and SDH in university curricula is regarded as an opportunity to address social problems. This approach addresses a broad cross section of the curriculum, especially in the subjects of public health and Primary Health Care (PHC), where community outreach generates greater internalization by students. The dominance of the biomedical model of study plans and practice scenarios focusing on disease and little emphasis on community outreach are factors that limit the inclusion of the approach. CONCLUSIONS: The inclusion of EF and SDH in university curricula in Colombia has primarily focused on increasing the knowledge of various subjects oriented towards understanding the social dynamics or comprehensiveness of health and disease and, in some programmes, through practical courses in community health and PHC. Increased integration of EF and SDH in subjects or modules with clinical orientation is recommended. PMID- 27006410 TI - Mapping primary health care renewal in South America. AB - BACKGROUND: Primary health care (PHC) renewal processes are currently ongoing in South America (SA), but their characteristics have not been systematically described. OBJECTIVE: The study aimed to describe and contrast the PHC approaches being implemented in SA to provide knowledge of current conceptions, models and challenges. METHODS: This multiple case study used a qualitative approach with technical visits to health ministries in order to apply key-informant interviews of 129 PHC national policy makers and 53 local managers, as well as field observation of 57 selected PHC providers and document analysis, using a common matrix for data collection and analysis. PHC approaches were analysed by triangulating sources using the following categories: PHC philosophy and conception, service provision organization, intersectoral collaboration and social participation. RESULTS: Primary health care models were identified in association with existing health system types and the dynamics of PHC renewal in each country. A neo-selective model was found in three countries where coverage is segmented by private and public regimes; here, individual and collective care are separated. A comprehensive approach similar to the Alma-Ata model was found in seven countries where the public sector predominates and individual, family and community care are coordinated under the responsibility of the same health care team. CONCLUSIONS: The process of implementing a renewed PHC approach is affected by how health systems are funded and organized. Both models face many obstacles. In addition, care system organization, intersectoral coordination and social participation are weak in most of the countries. PMID- 27006411 TI - Cognitive reflection and antibiotic prescribing for acute respiratory infections. AB - BACKGROUND: Variation in clinical decision-making could be explained by clinicians' tendency to make 'snap-decisions' versus making more reflective decisions. One common clinical decision with unexplained variation is the prescription of antibiotics for acute respiratory infections (ARIs). OBJECTIVE: We hypothesized that clinicians who tended toward greater cognitive reflection would be less likely to prescribe antibiotics for ARIs. METHODS: The Cognitive Reflection Test (CRT) is a psychological test with three questions with intuitive but incorrect answers that respondents reach if they do not consider the question carefully. The CRT is scored from 0 to 3, representing the number of correct answers. A higher score indicates greater cognitive reflection. We administered the CRT to 187 clinicians in 50 primary care practices. From billing and electronic health record data, we calculated clinician-level antibiotic prescribing rates for ARIs in 3 categories: all ARIs, antibiotic-appropriate ARIs and non-antibiotic-appropriate ARIs. RESULTS: A total of 57 clinicians (31%) scored 0 points on the CRT; 38 (20%) scored 1; 51 (27%) scored 2; and 41 (22%) scored 3. We found a roughly U-shaped association between cognitive reflection and antibiotic prescribing. The antibiotic prescribing rate for CRT scores of 0, 1, 2 and 3 for all ARIs (n = 37080 visits) was 32%, 26%, 25% and 30% (P = 0.10); for antibiotic-appropriate ARIs (n = 11220 visits) was 60%, 55%, 54% and 58% (P = 0.63); and for non-antibiotic-appropriate ARIs (n = 25860 visits) was 21%, 17%, 13% and 18%, respectively (P = 0.03). CONCLUSIONS: In contrast to our hypothesis, there appears to be a 'sweet-spot' of cognitive reflection for antibiotic prescribing for non-antibiotic-appropriate ARIs. Differences in clinicians' cognitive reflection may be associated with other variations in care. PMID- 27006413 TI - Incidence of Breakthrough Urinary Tract Infection in Hospitalized Infants Receiving Antibiotic Prophylaxis. AB - Urinary tract infections (UTIs) are a source of substantial morbidity in children in the neonatal intensive care unit. The incidence of UTIs that occur in critically ill infants during a course of antibiotic prophylaxis (i.e., breakthrough urinary tract infections [BUTIs]) is not known. We investigated the incidence of BUTI in a cohort of infants hospitalized on prophylactic antibiotics in neonatal intensive care units. Predictors of BUTI were evaluated using multivariable Cox regression. Out of 716 787 infants, 631 (0.09%) were prescribed 821 courses of antibiotic prophylaxis. Among this cohort, 60 infants (9.5%) suffered a total of 65 BUTIs. Of all prophylactic antibiotic courses, 65/821 (7.9%) were complicated by BUTI. Klebsiella, Enterobacter, and Escherichia coli species were the most common causes of BUTI. There was no statistically significant difference ( P = .78) in BUTI incidence among the 4 antibiotics assessed (amoxicillin, cephalexin, nitrofurantoin, or trimethoprim sulfamethoxazole). PMID- 27006412 TI - Nonadherence to guidelines for prescribing antiplatelet/anticoagulant therapy in patients with atrial fibrillation. AB - BACKGROUND: We have found no papers evaluating nonadherence to guidelines for the treatment of atrial fibrillation (AF), taking into account the two risk scales [C, congestive heart failure; H, hypertension; A, age; D, diabetes mellitus; S, stroke (CHADS2) and C, congestive heart failure; H, hypertension; A, age; D, diabetes mellitus; S, stroke; V, vascular disease; A, age; Sc, sex category (CHA2DS2-VASc)] and the two types of treatment that are recommended (antiplatelet/anticoagulant therapy). OBJECTIVE: To determine the extent of lack of adherence when prescribing anticoagulant and antiplatelet therapy to patients with AF and associated factors. METHODS: Cross-sectional, observational study of 144 patients with AF who visited the emergency department of Elda Hospital in 2013-14 (Spain). Main variable: the patient was prescribed a therapy different from that indicated by the guidelines (nonadherence) or not prescribed any therapy. Secondary variables: CHADS2, CHA2DS2-VASc, HAS-BLED, type of AF and symptoms related to AF. Multivariate models were constructed to identify the associated factors by calculating the adjusted odds ratios (OR). RESULTS: Nonadherence occurred in 90 patients [62.5%, 95% confidence interval (CI): 54.6 70.4%]. Associated factors were higher CHADS2 (OR = 1.30, 95% CI: 0.96-1.75, P = 0.091) and CHA2DS2-VASc (OR = 1.23, 95% CI: 1.02-1.47, P = 0.027), and lower HAS BLED (OR = 0.67, 95% CI: 0.49-0.91, P = 0.011). CONCLUSIONS: Nonadherence to guidelines was found in three out of every five patients. A greater cerebrovascular risk and a lower haemorrhagic risk were associated with this behaviour. Qualitative studies are needed to determine the causes. PMID- 27006414 TI - Neuropsychological Measures in the Diagnosis of ADHD in Preschool: Can Developmental Research Inform Diagnostic Practice? AB - OBJECTIVE: The diagnosis of ADHD in preschool is challenging. Behavioral ratings are less reliable, but the value of neuropsychological tests in the diagnosis of ADHD has been debated. METHOD: This article provides an overview of neuropsychological measures utilized in preschoolers with ADHD (3-5 years). In addition, the manuscript discusses the extent to which these measures have been tested for their diagnostic capacity. RESULTS: The diagnostic utility of computerized continuous performance tests and working memory subtests from IQ batteries has been demonstrated in a number of studies by assessing their psychometric properties, sensitivity, and specificity. However, findings from developmental and basic research attempting to describe risk factors that explain variance in ADHD show the most consistent associations of ADHD with measures of delay aversion. CONCLUSION: Results from developmental research could benefit studies that improve ADHD diagnosis at the individual level. It might be helpful to consider testing as a structured situation for behavioral observation by the clinician. PMID- 27006415 TI - Protection of the environment in existing exposure situations. AB - The International Commission on Radiological Protection (ICRP) described its approach to the protection of the environment and how it should be applied in Publication 124 The report expanded on the Commission's objectives for environmental protection, and how the Derived Consideration Reference Levels (DCRLs) apply within different exposure situations. DCRLs relate radiation effects to doses over and above their normal local background radiation levels, and consider different potential pathways of exposure for animals and plants. This paper will describe how the DCRLs may be used within existing exposure situations to better understand the potential impacts on animals and plants. In these circumstances, the Commission recommends that the aim be to reduce exposures to levels that are within the DCRL bands (or even below, depending upon the potential cost/benefits), but with full consideration of the radiological and non-radiological consequences of doing so. Using examples, this paper will demonstrate how this may be achieved in practice, bearing in mind the potential exposure of humans, animals and plants during and following any remediation attempted. PMID- 27006416 TI - Health and social care devolution: the Greater Manchester experiment. PMID- 27006417 TI - Infections in early life and premature acute coronary syndrome: A case-control study. AB - BACKGROUND: Infections in young children may affect the vasculature and initiate early atherosclerosis. Whether infections experienced in childhood play a part in adult clinical cardiovascular disease remains unclear. We investigated the association between infections in early life and the occurrence of premature coronary heart disease. METHODS: We conducted a population-based case-control study of 153 patients with a first acute coronary syndrome before the age of 56 years and 153 age- and sex-matched controls. Any history of severe infections in childhood and adolescence was obtained, together with clinical and laboratory measurements and other cardiovascular risk factors. We developed an infection score for the overall burden of early life infections. Conditional logistic regression was used to assess the associations. RESULTS: Infections experienced in early life increased the risk of acquiring acute coronary syndrome at a young age with an odds ratio (OR) of 2.67 (95% confidence interval (CI) 1.47-4.83, p = 0.001). After adjustments for traditional risk factors, lifestyle, dietary patterns, socio-economic status and parental history of cardiovascular events, these associations remained significant and changed only slightly. There was an indication for an interaction between infections in early life and current cardiovascular risk (Framingham Risk Score (FRS); p-interaction = 0.052). Within participants with a low FRS (<10%), the OR of early life infection for acute coronary syndrome was 1.49 (95% CI 0.72-3.08, p = 0.283); within participants with an intermediate FRS (10-20%), the OR was 4.35 (95% CI 1.60-11.84, p = 0.004); and within participants with a high FRS (>20%), the OR 10.00 (95% CI 1.21 82.51, p = 0.032). CONCLUSION: Infections in early life may partly explain premature coronary heart disease in adulthood and may potentiate traditional cardiovascular risk factor effects. PMID- 27006418 TI - Should doctors boycott working in Australia's immigration detention centres? PMID- 27006419 TI - Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial. AB - OBJECTIVE: To investigate the effects of dual-task balance training on postural performance in patients with multiple sclerosis as compared with single-task balance training. DESIGN: Double-blind, pretest-posttest, randomized controlled pilot trial. SETTING: Local Multiple Sclerosis Society. SUBJECTS: A total of 47 patients were randomly assigned to two equal groups labeled as single-task training and dual-task training groups. INTERVENTIONS: All patients received supervised balance training sessions, 3 times per week for 4 weeks. The patients in the single-task group performed balance activities, alone. However, patients in dual-task group practiced balance activities while simultaneously performing cognitive tasks. MAIN MEASURES: The 10-Meter Walk Test and Timed Up-and-Go under single-task and dual-task conditions, in addition to Activities-specific Balance Confidence, Berg Balance Scale, and Functional Gait Assessment were assessed pre , and post intervention and also 6-weeks after the end of intervention. RESULTS: Only 38 patients completed the treatment plan. There was no difference in the amount of improvement seen between the two study groups. In both groups there was a significant effect of time for dual-10 Meter Walk Test (F1, 36=11.33, p=0.002) and dual-Timed Up-and-Go (F1, 36=14.27, p=0.001) but not for their single-tasks. Moreover, there was a significant effect of time for Activities-specific Balance Confidence, Berg Balance Scale, and Functional Gait Assessment ( P<0.01). CONCLUSIONS: This pilot study did not show more benefits from undertaking dual task training than single-task training. A power analysis showed 71 patients per group would be needed to determine whether there was a clinically relevant difference for dual-task gait speed between the groups. PMID- 27006420 TI - The influence of tibial component malalignment on bone strain in revision total knee replacement. AB - Revision total knee replacement is a challenging surgical procedure typically associated with significant loss of bone stock in the proximal tibia. To increase the fixation stability, extended stems are frequently used for the tibial component in revision surgery. The design of the tibial stem influences the load transfer from tibial component to the surrounding bone and is cited as a possible cause for the clinically reported pain in the location of the stem-end. This study aimed to analyse the strain distribution of a fully cemented revision tibial component with a validated finite element model. The model was developed from a scanned composite tibia (Sawbones), with an implanted, fully cemented stemmed tibial component aligned to the mechanical axis of the tibia. Loading was applied to the tibial component with mediolateral compartment load distributions of 60:40 and 80:20. Three strain gauged composite tibias with implanted tibial components of the same design using the same loading distribution were tested to obtain experimental strains at five locations in the proximal tibia. The finite element model developed was validated against strain measurements obtained in the experimental study. The strains displayed similar patterns (R(2) = 0.988) and magnitudes with those predicted from the finite element model. The displacement of the stem-end from the natural mechanical axis in the finite element model demonstrated increased strains in the stem-end region with a close proximity of the distal stem with the cortical bone. The simulation of a mediolateral compartment load of 80:20 developed peak cortical strain values on the posterior medial side beneath the stem. This may possibly be related to the clinically reported pain at the stem-end. Furthermore, stem positioning in close proximity or contact with the posterior cortical bone is a contributory factor for an increase in distal strain. PMID- 27006421 TI - Musculoskeletal-based finite element analysis of femur after total hip replacement. AB - This article evaluates the effect of stress variation on adult femur following total hip replacement using musculoskeletal-based finite element analysis. The aim was to study the changes in stress distribution in the femur after total hip replacement by providing simulated in vivo loading and boundary conditions. The loading and boundary conditions were generated using a musculoskeletal modelling software 'AnyBody' and were applied on femur model, generated from the computed tomography (CT) scan data for standing posture of male patient. The results showed considerable variation in stress distribution pattern in the femur before and after total hip replacement, the metallic implant taking major loads of human body and transferring very less loads to the femur. PMID- 27006422 TI - Implantable power generation system utilizing muscle contractions excited by electrical stimulation. AB - An implantable power generation system driven by muscle contractions for supplying power to active implantable medical devices, such as pacemakers and neurostimulators, is proposed. In this system, a muscle is intentionally contracted by an electrical stimulation in accordance with the demands of the active implantable medical device for electrical power. The proposed system, which comprises a small electromagnetic induction generator, electrodes with an electrical circuit for stimulation and a transmission device to convert the linear motion of the muscle contractions into rotational motion for the magneto rotor, generates electrical energy. In an ex vivo demonstration using the gastrocnemius muscle of a toad, which was 28 mm in length and weighed 1.3 g, the electrical energy generated by the prototype exceeded the energy consumed for electrical stimulation, with the net power being 111 uW. It was demonstrated that the proposed implantable power generation system has the potential to replace implantable batteries for active implantable medical devices. PMID- 27006424 TI - Reply from Schonenberger et al. to the letter from Kofke and Sharma regarding "Sedation vs. Intubation for Endovascular Stroke TreAtment (SIESTA) - a randomized monocentric trial". PMID- 27006423 TI - Post-stroke dysphagia: A review and design considerations for future trials. AB - Post-stroke dysphagia (a difficulty in swallowing after a stroke) is a common and expensive complication of acute stroke and is associated with increased mortality, morbidity, and institutionalization due in part to aspiration, pneumonia, and malnutrition. Although most patients recover swallowing spontaneously, a significant minority still have dysphagia at six months. Although multiple advances have been made in the hyperacute treatment of stroke and secondary prevention, the management of dysphagia post-stroke remains a neglected area of research, and its optimal management, including diagnosis, investigation and treatment, have still to be defined. PMID- 27006425 TI - Stroke onset time estimation from multispectral quantitative magnetic resonance imaging in a rat model of focal permanent cerebral ischemia. AB - BACKGROUND: Quantitative T2 relaxation magnetic resonance imaging allows estimation of stroke onset time. AIMS: We aimed to examine the accuracy of quantitative T1 and quantitative T2 relaxation times alone and in combination to provide estimates of stroke onset time in a rat model of permanent focal cerebral ischemia and map the spatial distribution of elevated quantitative T1 and quantitative T2 to assess tissue status. METHODS: Permanent middle cerebral artery occlusion was induced in Wistar rats. Animals were scanned at 9.4T for quantitative T1, quantitative T2, and Trace of Diffusion Tensor (Dav) up to 4 h post-middle cerebral artery occlusion. Time courses of differentials of quantitative T1 and quantitative T2 in ischemic and non-ischemic contralateral brain tissue (DeltaT1, DeltaT2) and volumes of tissue with elevated T1 and T2 relaxation times (f1, f2) were determined. TTC staining was used to highlight permanent ischemic damage. RESULTS: DeltaT1, DeltaT2, f1, f2, and the volume of tissue with both elevated quantitative T1 and quantitative T2 (V(Overlap)) increased with time post-middle cerebral artery occlusion allowing stroke onset time to be estimated. V(Overlap) provided the most accurate estimate with an uncertainty of +/-25 min. At all times-points regions with elevated relaxation times were smaller than areas with Dav defined ischemia. CONCLUSIONS: Stroke onset time can be determined by quantitative T1 and quantitative T2 relaxation times and tissue volumes. Combining quantitative T1 and quantitative T2 provides the most accurate estimate and potentially identifies irreversibly damaged brain tissue. PMID- 27006426 TI - Doctor who gave expert advice in "shaken baby" cases is struck off. PMID- 27006427 TI - Did death certificates and a death review process agree on lung cancer cause of death in the National Lung Screening Trial? AB - BACKGROUND/AIMS: Randomized controlled trials frequently use death review committees to assign a cause of death rather than relying on cause of death information from death certificates. The National Lung Screening Trial, a randomized controlled trial of lung cancer screening with low-dose computed tomography versus chest X-ray for heavy and/or long-term smokers ages 55-74 years at enrollment, used a committee blinded to arm assignment for a subset of deaths to determine whether cause of death was due to lung cancer. METHODS: Deaths were selected for review using a pre-determined computerized algorithm. The algorithm, which considered cancers diagnosed during the trial, causes and significant conditions listed on the death certificate, and the underlying cause of death derived from death certificate information by trained nosologists, selected deaths that were most likely to represent a death due to lung cancer (either directly or indirectly) and deaths that might have been erroneously assigned lung cancer as the cause of death. The algorithm also selected deaths that might be due to adverse events of diagnostic evaluation for lung cancer. Using the review cause of death as the gold standard and lung cancer cause of death as the outcome of interest (dichotomized as lung cancer versus not lung cancer), we calculated performance measures of the death certificate cause of death. We also recalculated the trial primary endpoint using the death certificate cause of death. RESULTS: In all, 1642 deaths were reviewed and assigned a cause of death (42% of the 3877 National Lung Screening Trial deaths). Sensitivity of death certificate cause of death was 91%; specificity, 97%; positive predictive value, 98%; and negative predictive value, 89%. About 40% of the deaths reclassified to lung cancer cause of death had a death certificate cause of death of a neoplasm other than lung. Using the death certificate cause of death, the lung cancer mortality reduction was 18% (95% confidence interval: 4.2-25.0), as compared with the published finding of 20% (95% confidence interval: 6.7-26.7). CONCLUSION: Death review may not be necessary for primary-outcome analyses in lung cancer screening trials. If deemed necessary, researchers should strive to streamline the death review process as much as possible. PMID- 27006428 TI - Fever With Rash in a Healthy Adult. PMID- 27006430 TI - Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project. AB - BACKGROUND: Bisphosphonates and denosumab are well-established therapies to reduce the frequency and severity of skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications on bone pain is uncertain. AIM: To identify, critically appraise and synthesize existing evidence to answer the following questions: 'In adult patients with metastatic bone pain, what is the evidence that bisphosphonates and denosumab are effective and safe in controlling pain?' and 'What is the most appropriate schedule of bisphosphonate/denosumab administration to control bone pain?'. This review also updates the 2002 Cochrane review 'Bisphosphonates for the relief of pain secondary to bone metastases'. DESIGN: Standard systematic review and narrative synthesis. DATA SOURCES: MEDLINE, EMBASE and Cochrane CENTRAL databases were searched for relevant articles published through 31 January 2014. A manual search was also performed. Study inclusion criteria were: a) conducted in adult patients; b) randomized controlled trial or meta-analisys; c) reported efficacy of bisphosphonates or denosumab on pain and/or decribed side effects versus placebo or other bisphosphonate; and d) English language. RESULTS: The database search yielded 1585 studies, of which 43 (enrolling 8595 and 7590 patients, respectively, in bisphosphonate and denosumab trials) met the inclusion criteria. Twenty-two (79%) of the 28 placebo-controlled trials found no analgesic benefit for bisphosphonates. None of the denosumab studies assessed direct pain relief. CONCLUSION: Evidence to support an analgesic role for bisphosphonates and denosumab is weak. Bisphosphonates and denosumab appear to be beneficial in preventing pain by delaying the onset of bone pain rather than by producing an analgesic effect per se. PMID- 27006431 TI - Exploratory and Confirmatory Factor Analyses of Delirium Symptoms in a Sample of Nursing Home Residents. AB - OBJECTIVE: This study examined the latent constructs of delirium symptoms among nursing home (NH) residents in the United States. METHOD: Cross-sectional NH assessment data (Minimum Data Set 2.0) from the 2009 Medicare Current Beneficiary Survey were used. Data from two independent, randomly selected subsamples of residents >=65 years were analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). RESULTS: There were 367 and 366 individuals in the EFA and CFA, respectively. Assessment of multiple model fit statistics in CFA indicated that the two-factor structure provided better fit for the data than a one-factor solution. The two factors represented cognitive and behavioral latent constructs as suggested by the related literature. A correlation of .72 between these constructs suggested moderate discriminant validity. CONCLUSION: This finding emphasizes the importance of health care providers to be attentive to both cognitive and behavioral symptoms when diagnosing, treating, and managing delirium. PMID- 27006432 TI - Examining the Influence of Care-Recipient Resistance on Family Caregiver Emotional and Physical Well-Being: Average Frequency Versus Daily Fluctuation. AB - Although existing cross-sectional research suggests that dependent older family members' resistive behavior (care-recipient [CR] resistance: verbal or nonverbal rejection or resistance toward caregiver [CG] assistance) can be challenging for informal family CGs, we know little about the impact of the occurrence patterns of CR-resistance-average frequency versus daily fluctuation-on CG emotional and physical well-being. To document CGs' daily experiences with CR-resistance and their emotional and physical well-being, the present study applied short-term repeated measures, collecting data on 8 consecutive days from 63 CGs in Southern Arizona, the United States. Multilevel modeling of the daily data revealed that neither average frequency nor daily fluctuation in CR-resistance alone had a significant impact on CG emotional/physical health. However, the combination of experiencing relatively high frequency and high daily fluctuation in CR resistance was associated with significant increases in CG physical health symptoms ( b = .34, p < .01). Specifically, on days when a CG faced more CR resistance than his or her usual amount, significant increases in physical health symptoms existed for CGs with relatively high average frequency of CR-resistance, but not for CGs with relatively low average frequency of CR-resistance. Based on our results, it appears that monitoring and maintaining a reasonable level of CR resistance are effective strategies to maintain CG resilience to the negative impact of CR-resistance daily fluctuation. The findings are interpreted in light of Stress Theory, and recommendations for future research and practical interventions are offered. PMID- 27006433 TI - Medical Home Implementation Gaps for Seniors: Perceptions and Experiences of Primary Care Medical Practices. AB - OBJECTIVE: The study objective was to better understand specific implementation gaps for various aspects of patient-centered medical home (PCMH) care delivered to seniors. The study illuminates the physician and staff experience by focusing on how individuals make sense of and respond behaviorally to aspects of PCMH implementation. METHOD: Qualitative data from 51 in-depth, semi-structured interviews across six different National Committee for Quality Assurance (NCQA) accredited primary care practices were collected and analyzed. RESULTS: Physicians and staff identified PCMH implementation gaps for their seniors: (a) performing in-depth clinical assessments, (b) identifying seniors' life needs and linking them with community resources, and (c) care management and coordination, in particular self-management support for seniors. Prior experiences trying to perform these aspects of PCMH care for older adults produced collective understandings that led to inaction and avoidance by medical practices around the first two gaps, and proactive behavior that took strategic advantage of external incentives for addressing the third gap. CONCLUSION: Greater understanding of physician and staff's PCMH implementation experiences, and the learning that accumulates from these experiences, allows for a deeper understanding of how primary care practices choose to enact the medical home model for seniors on an everyday basis. PMID- 27006434 TI - Residential Segregation and Hypertension Prevalence in Black and White Older Adults. AB - PURPOSE: The purpose of this article was to assess segregation's role on race differences in hypertension among non-Hispanic Blacks and Whites aged 50 and over. METHOD: Hypertension was defined as systolic blood pressure (BP) >= 140 mmHg, diastolic BP >= 90 mmHg, or self-reported antihypertensive medication use. Segregation measures combined race, neighborhood racial composition, and individual and neighborhood poverty level. Logistic models produced odds ratios and 95% confidence intervals (CIs) for each segregation category, adjusting for health-related factors. RESULTS: Blacks in Black (OR = 2.54, CI = [1.61, 4.00]), White (OR = 2.56, CI = [1.24, 5.31]), and integrated neighborhoods (OR = 3.23, CI = [1.72, 6.03]) had greater odds of hypertension compared with Whites in White neighborhoods. Poor Whites in poor neighborhoods (OR = 1.74, CI = [1.09, 2.76]), nonpoor Blacks in nonpoor (OR = 3.03, CI = [1.79, 5.12]) and poor neighborhoods (OR = 4.08, CI = [2.16, 7.70]), and poor Blacks in nonpoor (OR = 4.35, CI = [2.17, 8.73]) and poor neighborhoods (OR = 2.75, CI = [1.74, 4.36]) had greater odds compared with nonpoor Whites in nonpoor neighborhoods. CONCLUSION: Interventions targeting hypertension among older adults should consider neighborhood compositions. PMID- 27006436 TI - In memory of Prof. Dr. Cengiz Utas (1959-2015). PMID- 27006437 TI - Mycobacterial Peritonitis in CAPD Patients in Limpopo: A 6-Year Cumulative Report from a Single Center in South Africa. AB - South Africa has one of the highest incidences of tuberculosis (TB) worldwide due to the ongoing human immunodeficiency virus (HIV) epidemic. There are, however, no reports on peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients due to Mycobacterium tuberculosis in South Africa. The aim of this study is to discuss our experience of tuberculous peritonitis in CAPD patients from a rural endemic area of South Africa. This is a retrospective descriptive study of CAPD patients diagnosed with mycobacterium peritonitis infection from January 2008 to August 2014 at the Limpopo Kidney and Dialysis Centre (LKDC) in South Africa. The diagnosis of peritonitis was based on the International Society for Peritoneal Dialysis (ISPD) 2010 recommendations. Peritoneal fluid samples were collected in BACTEC Myco/F Lytic Culture Vials (Becton, Dickinson and Company, Dublin, Ireland). Tenckhoff catheter tips were sent for acid-fast bacilli (AFB) smear and TB culture. Mycobacterium infection was considered in patients with clinical features of peritonitis if 1) AFB smear or TB culture was positive or 2) if the patient was smear- or culture-negative but had suggestive radiological features of TB in the lungs or abdomen or 3) if the patient improved clinically following treatment with anti-tuberculous drugs. Of 170 patients on CAPD for the period reviewed, 12 (7.1%) were diagnosed and treated for mycobacterial peritonitis. There was an equal number of males and females, and all the patients were Black Africans with a mean age of 35.4 years (17-51 years). Eight of the 12 patients (66.7%) had had previous episodes of non-tuberculous peritonitis. Four patients (33.3%) had elevated white blood cell count (WCC) while 9 had higher polymorph count in the PD fluid than lymphocyte count. Mycobacterial organism was confirmed in 9/12 (75%), while the diagnosis was made on clinical and radiological features in the remaining 3 patients. Seven patients (58.3%) died, 10 patients were permanently transferred to hemodialysis (HD), 1 patient returned to PD after a short stay on HD, 1 patient died after 2 years on HD due to lack of further access to dialysis, and in 1 patient, the catheter could not be removed before death. This case series corroborates findings from other previous series that mycobacterial infection in PD patients carries a high mortality and can often pose a diagnostic challenge to attending clinicians. Clinicians should have a high index of suspicion for mycobacterial peritonitis in CAPD patients with features of peritonitis who do not respond promptly to conventional anti microbial agents. We feel that the recommendation about catheter removal during mycobacterial peritonitis should be revisited, as it had no impact on our patients' outcome. PMID- 27006438 TI - Regular Deworming: A Missed Opportunity to Prevent Peritoneal Dialysis-Related Infections in Children. AB - Chronic peritoneal dialysis (PD) is a common dialysis treatment modality used to treat children with end-stage renal disease. Dialysis-related infections are the leading cause of technique failure. Enterobius vermicularis infestation indirectly increases the infection rate by causing pruritus around the anus, especially at night. We observed a significant decrease in the total infection rate (2.3 vs 5.4 per patient-year) following regular deworming over a 1-year study period. Regular deworming may be considered to prevent secondary bacterial infections in children on chronic PD. PMID- 27006439 TI - A Rare Case of Peritoneal Dialysis-Associated Peritonitis with Sphingomonas koreensis. AB - Sphingomonas species are ubiquitous gram-negative, aerobic bacteria frequently found in aquatic environments such as drinking water and very seldom in hemodialysis fluids or supposedly sterile drug solutions. Human infections with the gram-negative Sphingomonas species are rare and peritonitis with these organisms even rarer. Here we report a case of polymicrobial peritonitis due to Sphingomonas koreensis and Escherichia coli in a patient undergoing peritoneal dialysis (PD). PMID- 27006440 TI - Comparison of Disinfection Procedures on the Catheter Adapter-Transfer Set Junction. AB - Peritonitis is a significant complication of peritoneal dialysis (PD), contributing to mortality and technique failure. Suboptimal disinfection and/or a loose connection at the catheter adapter-transfer set junction are forms of touch contamination that can compromise the integrity of the sterile fluid path and lead to peritonitis. Proper use of the right disinfectants for connections at the PD catheter adapter-transfer set interface can help eliminate bacteria at surface interfaces, secure connections, and prevent bacteria from entering into the sterile fluid pathway. Three studies were conducted to assess the antibacterial effects of various disinfecting agents and procedures, and ensuing security of the catheter adapter-transfer set junction. An open-soak disinfection procedure with 10% povidone iodine improves disinfection and tightness/security of catheter adapter-transfer set connection. PMID- 27006441 TI - Ultrafiltration Failure and Impaired Sodium Sieving During Long-Term Peritoneal Dialysis: More Than Aquaporin Dysfunction? AB - Fifteen years ago, our group reported the case of a 67-year-old man on peritoneal dialysis for 11 years, in whom ultrafiltration failure and impaired sodium sieving were associated with an apparently normal expression of aquaporin-1 (AQP1) water channels in peritoneal capillaries. At that time, AQP1 dysfunction was suggested as the cause of impaired free-water transport. However, recent data from computer simulations, and structural and functional analysis of the peritoneal membrane of patients with encapsulating peritoneal sclerosis, demonstrated that changes in the peritoneal interstitium directly alter osmotic water transport. In light of these insights, we challenge the initial hypothesis and provide several lines of evidence supporting the diagnosis of encapsulating peritoneal sclerosis in this patient and suggesting that severe peritoneal fibrosis accounted for the loss of osmotic conductance developed during the course of peritoneal dialysis. PMID- 27006443 TI - Treatment with Povidone-Iodine of Pleural Effusion Due to Diaphragmatic Defect in a Patient Undergoing Peritoneal Dialysis. PMID- 27006442 TI - Importance of Neurogenic Bladder as a Cause of Drainage Failure. PMID- 27006444 TI - Rapid Equilibration Rates in Most Small Babies on Acute Peritoneal Dialysis. PMID- 27006446 TI - Preconditioning-induced CXCL12 upregulation minimizes leukocyte infiltration after stroke in ischemia-tolerant mice. AB - Repetitive hypoxic preconditioning creates long-lasting, endogenous protection in a mouse model of stroke, characterized by reductions in leukocyte-endothelial adherence, inflammation, and infarct volumes. The constitutively expressed chemokine CXCL12 can be upregulated by hypoxia and limits leukocyte entry into brain parenchyma during central nervous system inflammatory autoimmune disease. We therefore hypothesized that the sustained tolerance to stroke induced by repetitive hypoxic preconditioning is mediated, in part, by long-term CXCL12 upregulation at the blood-brain barrier (BBB). In male Swiss Webster mice, repetitive hypoxic preconditioning elevated cortical CXCL12 protein levels, and the number of cortical CXCL12+ microvessels, for at least two weeks after the last hypoxic exposure. Repetitive hypoxic preconditioning-treated mice maintained more CXCL12-positive vessels than untreated controls following transient focal stroke, despite cortical decreases in CXCL12 mRNA and protein. Continuous administration of the CXCL12 receptor (CXCR4) antagonist AMD3100 for two weeks following repetitive hypoxic preconditioning countered the increase in CXCL12 positive microvessels, both prior to and following stroke. AMD3100 blocked the protective post-stroke reductions in leukocyte diapedesis, including macrophages and NK cells, and blocked the protective effect of repetitive hypoxic preconditioning on lesion volume, but had no effect on blood-brain barrier dysfunction. These data suggest that CXCL12 upregulation prior to stroke onset, and its actions following stroke, contribute to the endogenous, anti-inflammatory phenotype induced by repetitive hypoxic preconditioning. PMID- 27006445 TI - Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells. AB - RATIONALE: Endothelial injury is an initial mechanism mediating cardiovascular disease. OBJECTIVE: Here, we investigated the effect of hyperhomocysteinemia on programed cell death in endothelial cells (EC). METHODS AND RESULTS: We established a novel flow-cytometric gating method to define pyrotosis (Annexin V( )/Propidium iodide(+)). In cultured human EC, we found that: (1) homocysteine and lipopolysaccharide individually and synergistically induced inflammatory pyroptotic and noninflammatory apoptotic cell death; (2) homocysteine/lipopolysaccharide induced caspase-1 activation before caspase-8, caspase-9, and caspase-3 activations; (3) caspase-1/caspase-3 inhibitors rescued homocysteine/lipopolysaccharide-induced pyroptosis/apoptosis, but caspase 8/caspase-9 inhibitors had differential rescue effect; (4) homocysteine/lipopolysaccharide-induced nucleotide-binding oligomerization domain, and leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) protein caused NLRP3-containing inflammasome assembly, caspase-1 activation, and interleukin (IL)-1beta cleavage/activation; (5) homocysteine/lipopolysaccharide elevated intracellular reactive oxygen species, (6) intracellular oxidative gradient determined cell death destiny as intermediate intracellular reactive oxygen species levels are associated with pyroptosis, whereas high reactive oxygen species corresponded to apoptosis; (7) homocysteine/lipopolysaccharide induced mitochondrial membrane potential collapse and cytochrome-c release, and increased B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 ratio which were attenuated by antioxidants and caspase-1 inhibitor; and (8) antioxidants extracellular superoxide dismutase and catalase prevented homocysteine/lipopolysaccharide -induced caspase-1 activation, mitochondrial dysfunction, and pyroptosis/apoptosis. In cystathionine beta-synthase-deficient (Cbs(-/-)) mice, severe hyperhomocysteinemia-induced caspase-1 activation in isolated lung EC and caspase-1 expression in aortic endothelium, and elevated aortic caspase-1, caspase-9 protein/activity and B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 ratio in Cbs(-/-) aorta and human umbilical vein endothelial cells. Finally, homocysteine-induced DNA fragmentation was reversed in caspase-1(-/-) EC. Hyperhomocysteinemia-induced aortic endothelial dysfunction was rescued in caspase-1(-/-) and NLRP3(-/-) mice. CONCLUSIONS: Hyperhomocysteinemia preferentially induces EC pyroptosis via caspase-1-dependent inflammasome activation leading to endothelial dysfunction. We termed caspase-1 responsive pyroptosis and apoptosis as pyrop-apoptosis. PMID- 27006448 TI - Identification of carboxypeptidase X (CPX)-1 as a positive regulator of adipogenesis. AB - Adipose tissue expansion occurs through a combination of hypertrophy of existing adipocytes and generation of new adipocytes via the process of hyperplasia, which involves the proliferation and subsequent differentiation of preadipocytes. Deficiencies in hyperplasia contribute to adipose tissue dysfunction and the association of obesity with chronic cardiometabolic diseases. Thus, increased understanding of hyperplastic pathways may be expected to afford novel therapeutic strategies. We have reported that fibroblast growth factor (FGF)-1 promotes proliferation and differentiation of human preadipocytes and recently demonstrated that bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is a central, proximal effector. Herein, we describe the identification and characterization of carboxypeptidase X (CPX)-1, a secreted collagen-binding glycoprotein, as a novel downstream effector in human primary and Simpson-Golabi Behmel syndrome preadipocytes. CPX-1 expression increased after treatment of preadipocytes with FGF-1, BAMBI knockdown, or induction of differentiation. CPX-1 knockdown compromised preadipocyte differentiation coincident with reduced collagen expression. Furthermore, preadipocytes differentiated on matrix derived from CPX-1 knockdown cells exhibited reduced Glut4 expression and insulin stimulated glucose uptake. Finally, CPX-1 expression was increased in adipose tissue from obese mice and humans. Collectively, these findings establish CPX-1 as a positive regulator of adipogenesis situated downstream of FGF-1/BAMBI that may contribute to hyperplastic adipose tissue expansion via affecting extracellular matrix remodeling.-Kim, Y.-H., Barclay, J. L., He, J., Luo, X., O'Neill, H. M., Keshvari, S., Webster, J. A., Ng, C., Hutley, L. J., Prins, J. B., Whitehead, J. P. Identification of carboxypeptidase X (CPX)-1 as a positive regulator of adipogenesis. PMID- 27006447 TI - Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. AB - Lysophosphatidic acid (LPA) is an important mediator of pulmonary fibrosis. In blood and multiple tumor types, autotaxin produces LPA from lysophosphatidylcholine (LPC) via lysophospholipase D activity, but alternative enzymatic pathways also exist for LPA production. We examined the role of autotaxin (ATX) in pulmonary LPA production during fibrogenesis in a bleomycin mouse model. We found that bleomycin injury increases the bronchoalveolar lavage (BAL) fluid levels of ATX protein 17-fold. However, the LPA and LPC species that increase in BAL of bleomycin-injured mice were discordant, inconsistent with a substrate-product relationship between LPC and LPA in pulmonary fibrosis. LPA species with longer chain polyunsaturated acyl groups predominated in BAL fluid after bleomycin injury, with 22:5 and 22:6 species accounting for 55 and 16% of the total, whereas the predominant BAL LPC species contained shorter chain, saturated acyl groups, with 16:0 and 18:0 species accounting for 56 and 14% of the total. Further, administration of the potent ATX inhibitor PAT-048 to bleomycin-challenged mice markedly decreased ATX activity systemically and in the lung, without effect on pulmonary LPA or fibrosis. Therefore, alternative ATX independent pathways are likely responsible for local generation of LPA in the injured lung. These pathways will require identification to therapeutically target LPA production in pulmonary fibrosis.-Black, K. E., Berdyshev, E., Bain, G., Castelino, F. V., Shea, B. S., Probst, C. K., Fontaine, B. A., Bronova, I., Goulet, L., Lagares, D., Ahluwalia, N., Knipe, R. S., Natarajan, V., Tager, A. M. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. PMID- 27006449 TI - Phenotypic transformation of intimal and adventitial lymphatics in atherosclerosis: a regulatory role for soluble VEGF receptor 2. AB - The role of lymphatics in atherosclerosis is not yet understood. Here, we investigate lymphatic growth dynamics and marker expression in atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. The prolymphangiogenic growth factor, VEGF-C, was elevated in atherosclerotic aortic walls. Despite increased VEGF-C, we found that adventitial lymphatics regress during the course of formation of atherosclerosis (P < 0.01). Similar to lymphatic regression, the number of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1(+)) macrophages decreased in the aortic adventitia of apoE(-/-) mice with atherosclerosis (P < 0.01). Intimal lymphatics in the atherosclerotic lesions exhibited an atypical phenotype, with the expression of podoplanin and VEGF receptor 3 (VEGFR-3) but not of LYVE-1 and prospero homeobox protein 1. In the aortas of atherosclerotic animals, we found markedly increased soluble VEGFR-2. We hypothesized that the elevated soluble VEGFR-2 that was found in the aortas of apoE(-/-) mice with atherosclerosis binds to and diminishes the activity of VEGF C. This trapping mechanism explains, despite increased VEGF-C in the atherosclerotic aortas, how adventitial lymphatics regress. Lymphatic regression impedes the drainage of lipids, growth factors, inflammatory cytokines, and immune cells. Insufficient lymphatic drainage could thus exacerbate atherosclerosis formation. Our study contributes new insights to previously unknown dynamic changes of adventitial lymphatics. Targeting soluble VEGFR-2 in atherosclerosis may provide a new strategy for the liberation of endogenous VEGF C and the prevention of lymphatic regression.-Taher, M., Nakao, S., Zandi, S., Melhorn, M. I., Hayes, K. C., Hafezi-Moghadam, A. Phenotypic transformation of intimal and adventitial lymphatics in atherosclerosis: a regulatory role for soluble VEGF receptor 2. PMID- 27006451 TI - Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury. AB - The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant response and xenobiotic metabolism. Activation of the Nrf2 signaling pathway has been demonstrated to confer protection against environmental insults and prevent disease or inhibit the progression of diseases related to oxidative stress. In an attempt to identify novel improved Nrf2 inducers for systemic protection against tissue damage by environmental insults, we identified artemisitene as a novel Nrf2 activator using antioxidant responsive element luciferase assay in MDA-MB-231 cells. Further studies suggest that artemisitene activates Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability. In Nrf2 wild-type mice, systemic administration of artemisitene strongly inhibits bleomycin-induced lung damage. Artemisitene represents a novel class of Nrf2 inducer, and artemisitene-based therapeutic approach targeting Nrf2 may also provide antioxidant protection for humans against tissue damage by toxic chemicals.-Chen, W., Li, S., Li, J., Zhou, W., Wu, S., Xu, S., Cui, K., Zhang, D. D., Liu, B. Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury. PMID- 27006450 TI - Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension. AB - Activation of the mammalian target of rapamycin complex 1 (mTORC1) subunit Raptor induces cell growth and is a downstream target of Akt. Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone-Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU-5416/hypoxia-PAH rats and monocrotaline-PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone-Raptor signaling in human PASMCs. Aldosterone (10(-9) to 10(-7) M) increased Akt/mTOR/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor-small interfering RNA or treated with spironolactone/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival in vitro Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine-monomethoxy polyethylene glycol that was formulated with Raptor-small interfering RNA plus spironolactone in vivo, which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH in vivo Up-regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.-Aghamohammadzadeh, R., Zhang, Y.-Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.-M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension. PMID- 27006452 TI - Efficacy of Upper Extremity Robotic Therapy in Subacute Poststroke Hemiplegia: An Exploratory Randomized Trial. AB - BACKGROUND AND PURPOSE: Our aim was to study the efficacy of robotic therapy as an adjuvant to standard therapy during poststroke rehabilitation. METHODS: Prospective, open, blinded end point, randomized, multicenter exploratory clinical trial in Japan of 60 individuals with mild to moderate hemiplegia 4 to 8 weeks post stroke randomized to receive standard therapy plus 40 minutes of either robotic or self-guided therapy for 6 weeks (7 days/week). Upper extremity impairment before and after intervention was measured using the Fugl-Meyer assessment, Wolf Motor Function Test, and Motor Activity Log. RESULTS: Robotic therapy significantly improved Fugl-Meyer assessment flexor synergy (2.1+/-2.7 versus -0.1+/-2.4; P<0.01) and proximal upper extremity (4.8+/-5.0 versus 1.9+/ 5.5; P<0.05) compared with self-guided therapy. No significant changes in Wolf Motor Function Test or Motor Activity Log were observed. Robotic therapy also significantly improved Fugl-Meyer assessment proximal upper extremity among low functioning patients (baseline Fugl-Meyer assessment score <30) and among patients with Wolf Motor Function Test >=120 at baseline compared with self guided therapy (P<0.05 for both). CONCLUSIONS: Robotic therapy as an adjuvant to standard rehabilitation may improve upper extremity recovery in moderately impaired poststroke patients. Results of this exploratory study should be interpreted with caution. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/. Unique identifier: UMIN000001619. PMID- 27006453 TI - Arterial Tortuosity: An Imaging Biomarker of Childhood Stroke Pathogenesis? AB - BACKGROUND AND PURPOSE: Arteriopathy is the leading cause of childhood arterial ischemic stroke. Mechanisms are poorly understood but may include inherent abnormalities of arterial structure. Extracranial dissection is associated with connective tissue disorders in adult stroke. Focal cerebral arteriopathy is a common syndrome where pathophysiology is unknown but may include intracranial dissection or transient cerebral arteriopathy. We aimed to quantify cerebral arterial tortuosity in childhood arterial ischemic stroke, hypothesizing increased tortuosity in dissection. METHODS: Children (1 month to 18 years) with arterial ischemic stroke were recruited within the Vascular Effects of Infection in Pediatric Stroke (VIPS) study with controls from the Calgary Pediatric Stroke Program. Objective, multi-investigator review defined diagnostic categories. A validated imaging software method calculated the mean arterial tortuosity of the major cerebral arteries using 3-dimensional time-of-flight magnetic resonance angiographic source images. Tortuosity of unaffected vessels was compared between children with dissection, transient cerebral arteriopathy, meningitis, moyamoya, cardioembolic strokes, and controls (ANOVA and post hoc Tukey). Trauma-related versus spontaneous dissection was compared (Student t test). RESULTS: One hundred fifteen children were studied (median, 6.8 years; 43% women). Age and sex were similar across groups. Tortuosity means and variances were consistent with validation studies. Tortuosity in controls (1.346+/-0.074; n=15) was comparable with moyamoya (1.324+/-0.038; n=15; P=0.998), meningitis (1.348+/-0.052; n=11; P=0.989), and cardioembolic (1.379+/-0.056; n=27; P=0.190) cases. Tortuosity was higher in both extracranial dissection (1.404+/-0.084; n=22; P=0.021) and transient cerebral arteriopathy (1.390+/-0.040; n=27; P=0.001) children. Tortuosity was not different between traumatic versus spontaneous dissections (P=0.70). CONCLUSIONS: In children with dissection and transient cerebral arteriopathy, cerebral arteries demonstrate increased tortuosity. Quantified arterial tortuosity may represent a clinically relevant imaging biomarker of vascular biology in pediatric stroke. PMID- 27006455 TI - Chasing Ebola through the Endosomal Labyrinth. AB - During virus entry, the surface glycoprotein of Ebola virus (EBOV) undergoes a complex set of transformations within the endosomal network. Tools to study EBOV entry have been limited to static immunofluorescence or biochemical and functional analysis. In a recent article inmBio, Spence et al. reported a novel, live-cell-imaging method that tracks this transformational journey of EBOV in real time [J. S. Spence, T. B. Krause, E. Mittler, R. K. Jangra, and K. Chandran, mBio 7(1):e01857-15, 2016, http://dx.doi.org/10.1128/mBio.01857-15]. The assay validates known mechanisms of EBOV entry and sheds light on some novel intricacies. Direct evidence supports the hypothesis that fusion is a rare event that starts in maturing early endosomes, is completed in late endosomes, and occurs entirely in Niemann-Pick C1 (NPC1)-positive (NPC1(+)) compartments. The study demonstrated that lipid mixing and productive fusion are temporally decoupled, with different energetic barriers and a protease-dependent step between the two events. Analysis of the mechanism of action of an important class of EBOV neutralizing antibodies, such as KZ52 and ZMapp, provides direct evidence that these antibodies act by inhibiting the membrane fusion. PMID- 27006454 TI - Recombinant Osteopontin Stabilizes Smooth Muscle Cell Phenotype via Integrin Receptor/Integrin-Linked Kinase/Rac-1 Pathway After Subarachnoid Hemorrhage in Rats. AB - BACKGROUND AND PURPOSE: Recombinant osteopontin (rOPN) has been reported to be neuroprotective in stroke animal models. The purpose of this study is to investigate a potential role and mechanism of nasal administration of rOPN on preserving the vascular smooth muscle phenotype in early brain injury after subarachnoid hemorrhage (SAH). METHODS: One hundred and ninety-two male adult Sprague-Dawley rats were used. The SAH model was induced by endovascular perforation. Integrin-linked kinase small interfering RNA was intracerebroventricularly injected 48 hours before SAH. The integrin receptor antagonist fibronectin-derived peptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), focal adhesion kinase inhibitor Fib-14, and Rac-1 inhibitor NSC23766 were administered 1 hour before SAH induction. rOPN was administered via the intracerebroventricular and nasal route after SAH. SAH grade, neurological scores, brain water content, brain swelling, hematoxylin and eosin staining, India ink angiography, Western blots, and immunofluorescence were used to study the mechanisms of rOPN on the vascular smooth muscle phenotypic transformation. RESULTS: The marker proteins of vascular smooth muscle phenotypic transformation alpha-smooth muscle actin decreased and embryonic smooth muscle myosin heavy chain (SMemb) increased significantly at 24 and 72 hours in the cerebral arteries after SAH. rOPN prevented the changes of alpha-smooth muscle actin and SMemb and significantly alleviated neurobehavioral dysfunction, increased the cross sectional area and the lumen diameter of the cerebral arteries, reduced the brain water content and brain swelling, and improved the wall thickness of cerebral arteries. These effects of rOPN were abolished by GRGDSP, integrin-linked kinase small interfering RNA, and NSC23766. Intranasal application of rOPN at 3 hours after SAH also reduced neurological deficits. CONCLUSIONS: rOPN prevented the vascular smooth muscle phenotypic transformation and improved the neurological outcome, which was possibly mediated by the integrin receptor/integrin-linked kinase/Rac-1 pathway. PMID- 27006457 TI - ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection. AB - Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram-positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to anin vitrotranslation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosomein vitro To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection.IMPORTANCEAntimicrobial resistance ranks among the greatest threats currently facing human health. Elucidation of the mechanisms by which microorganisms resist the effect of antibiotics is central to understanding the biology of this phenomenon and has the potential to inform the development of new drugs capable of blocking or circumventing resistance. Members of the ABC-F family, which includelsa(A),msr(A),optr(A), andvga(A), collectively yield resistance to a broader range of clinically significant antibiotic classes than any other family of resistance determinants, although their mechanism of action has been controversial since their discovery 25 years ago. Here we present the first direct evidence that proteins of the ABC-F family act to protect the bacterial ribosome from antibiotic-mediated inhibition. PMID- 27006456 TI - Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis. AB - While significant protection from pneumococcal disease has been achieved by the use of polysaccharide and polysaccharide-protein conjugate vaccines, capsule independent protection has been limited by serotype replacement along with disease caused by nonencapsulatedStreptococcus pneumoniae(NESp). NESp strains compose approximately 3% to 19% of asymptomatic carriage isolates and harbor multiple antibiotic resistance genes. Surface proteins unique to NESp enhance colonization and virulence despite the lack of a capsule even though the capsule has been thought to be required for pneumococcal pathogenesis. Genes for pneumococcal surface proteins replace the capsular polysaccharide (cps) locus in some NESp isolates, and these proteins aid in pneumococcal colonization and otitis media (OM). NESp strains have been isolated from patients with invasive and noninvasive pneumococcal disease, but noninvasive diseases, specifically, conjunctivitis (85%) and OM (8%), are of higher prevalence. Conjunctival strains are commonly of the so-called classical NESp lineages defined by multilocus sequence types (STs) ST344 and ST448, while sporadic NESp lineages such as ST1106 are more commonly isolated from patients with other diseases. Interestingly, sporadic lineages have significantly higher rates of recombination than classical lineages. Higher rates of recombination can lead to increased acquisition of antibiotic resistance and virulence factors, increasing the risk of disease and hindering treatment. NESp strains are a significant proportion of the pneumococcal population, can cause disease, and may be increasing in prevalence in the population due to effects on the pneumococcal niche caused by pneumococcal vaccines. Current vaccines are ineffective against NESp, and further research is necessary to develop vaccines effective against both encapsulated and nonencapsulated pneumococci. PMID- 27006458 TI - Investigation of the Genetics and Biochemistry of Roseobacticide Production in the Roseobacter Clade Bacterium Phaeobacter inhibens. AB - Roseobacterclade bacteria are abundant in surface waters and are among the most metabolically diverse and ecologically significant species. This group includes opportunistic symbionts that associate with micro- and macroalgae. We have proposed that one representative member,Phaeobacter inhibens, engages in a dynamic symbiosis with the microalgaEmiliania huxleyi In one phase, mutualistically beneficial molecules are exchanged, including theRoseobacter produced antibiotic tropodithietic acid (TDA), which is thought to protect the symbiotic interaction. In an alternative parasitic phase, triggered by algal senescence, the bacteria produce potent algaecides, the roseobacticides, which kill the algal host. Here, we employed genetic and biochemical screens to identify the roseobacticide biosynthetic gene cluster. By using a transposon mutagenesis approach, we found that genes required for TDA synthesis-thetdaoperon andpaacatabolon-are also necessary for roseobacticide production. Thus, in contrast to the one-cluster-one-compound paradigm, thetdagene cluster can generate two sets of molecules with distinct structures and bioactivities. We further show that roseobacticide production is quorum sensing regulated via anN acyl homoserine lactone signal (3-OH-C10-HSL). To ensure tight regulation of algaecide production, and thus of a lifestyle switch from mutualism to parasitism, roseobacticide biosynthesis necessitates the presence of both an algal senescence molecule and a quorum sensing signal.IMPORTANCEMarineRoseobacterspecies are abundant in the oceans and engage in symbiotic interactions with microscopic algae. One member,P. inhibens, produces the antibiotic TDA and a growth hormone thought to protect and promote algal growth. However, in the presence of molecules released by senescing algae, the bacteria produce potent algaecides, the roseobacticides, which kill the host. We examined the regulatory networks and biosynthetic genes required for roseobacticide production. We found thatP. inhibensuses largely the same set of genes for production of both TDA and roseobacticides, thus providing a rare case in which one gene cluster synthesizes two structurally and functionally distinct molecules. Moreover, we found roseobacticide production to be regulated by quorum sensing. Thus, two small molecules, the algal metabolite and the quorum-sensing signal, ensure tight control in the production of roseobacticides. These results highlight the role of small molecules in regulating microbial symbioses. PMID- 27006460 TI - The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues. AB - Moraxella catarrhalis is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step in M. catarrhalis colonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role of M. catarrhalis interactions with collagens from various angles. Clinical isolates (n= 43) were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins.M. catarrhalis-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD) model was used to estimate the adherence of M. catarrhalis in vivo. We found that all M. catarrhalis clinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesins ubiquitous surface protein A2(UspA2) and UspA2H were identified as major collagen-binding receptors.M. catarrhalis wild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that theM. catarrhalisUspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease. IMPORTANCE: The respiratory tract pathogen Moraxella catarrhalis adheres to the host by interacting with several components, including the ECM. Collagen accounts for 30% of total body proteins, and therefore, bacterial adherence to abundant host collagens mediates bacterial persistence and colonization. In this study, we characterized previously unknown M. catarrhalis-dependent interactions with host collagens and found that the trimeric autotransporter adhesins ubiquitous surface protein A2(UspA2) and UspA2H are highly important. Our observations also suggested that collagen-mediated adherence ofM. catarrhalis is indispensable for bacterial survival in the host, as exemplified by a mouse COPD model. PMID- 27006459 TI - Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131. AB - Escherichia colisequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection (n= 215) of sequenced ST131E. coliisolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades, C1/H30R and C2/H30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/H30Rx clade driven by the acquisition of ablaCTX-M-15 containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX M resistance plasmids and chromosomal integration ofblaCTX-Mwithin subclusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed among ST131, theblaCTX-M 14/14-likegroup. The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages ofE. coli These data also highlight the global imperative to reduce specific antibiotic selection pressures and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages. IMPORTANCE: Escherichia coli, perennially a major bacterial pathogen, is becoming increasingly difficult to manage due to emerging resistance to all preferred antimicrobials. Resistance is concentrated within specificE. colilineages, such as sequence type 131 (ST131). Clarification of the genetic basis for clonally associated resistance is key to devising intervention strategies. We used high-resolution genomic analysis of a large global collection of ST131 isolates to define the evolutionary history of extended-spectrum beta lactamase production in ST131. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance elements. Both global distribution and regional segregation were evident. The diversity of resistance element acquisition and propagation within ST131 indicates a need for control and surveillance strategies that target both bacterial strains and mobile genetic elements. PMID- 27006461 TI - Discovery of the Elusive UDP-Diacylglucosamine Hydrolase in the Lipid A Biosynthetic Pathway in Chlamydia trachomatis. AB - Constitutive biosynthesis of lipid A via the Raetz pathway is essential for the viability and fitness of Gram-negative bacteria, includingChlamydia trachomatis Although nearly all of the enzymes in the lipid A biosynthetic pathway are highly conserved across Gram-negative bacteria, the cleavage of the pyrophosphate group of UDP-2,3-diacyl-GlcN (UDP-DAGn) to form lipid X is carried out by two unrelated enzymes: LpxH in beta- and gammaproteobacteria and LpxI in alphaproteobacteria. The intracellular pathogenC. trachomatislacks an ortholog for either of these two enzymes, and yet, it synthesizes lipid A and exhibits conservation of genes encoding other lipid A enzymes. Employing a complementation screen against aC. trachomatisgenomic library using a conditional-lethallpxHmutantEscherichia colistrain, we have identified an open reading frame (Ct461, renamedlpxG) encoding a previously uncharacterized enzyme that complements the UDP-DAGn hydrolase function inE. coliand catalyzes the conversion of UDP-DAGn to lipid Xin vitro LpxG shows little sequence similarity to either LpxH or LpxI, highlighting LpxG as the founding member of a third class of UDP-DAGn hydrolases. Overexpression of LpxG results in toxic accumulation of lipid X and profoundly reduces the infectivity ofC. trachomatis, validating LpxG as the long-sought after UDP-DAGn pyrophosphatase in this prominent human pathogen. The complementation approach presented here overcomes the lack of suitable genetic tools forC. trachomatisand should be broadly applicable for the functional characterization of other essentialC. trachomatisgenes.IMPORTANCEChlamydia trachomatisis a leading cause of infectious blindness and sexually transmitted disease. Due to the lack of robust genetic tools, the functions of manyChlamydiagenes remain uncharacterized, including the essential gene encoding the UDP-DAGn pyrophosphatase activity for the biosynthesis of lipid A, the membrane anchor of lipooligosaccharide and the predominant lipid species of the outer leaflet of the bacterial outer membrane. We designed a complementation screen against theC. trachomatisgenomic library using a conditional-lethal mutant ofE. coliand identified the missing essential gene in the lipid A biosynthetic pathway, which we designatedlpxG We show that LpxG is a member of the calcineurin like phosphatases and displays robust UDP-DAGn pyrophosphatase activityin vitro Overexpression of LpxG inC. trachomatisleads to the accumulation of the predicted lipid intermediate and reduces bacterial infectivity, validating thein vivofunction of LpxG and highlighting the importance of regulated lipid A biosynthesis inC. trachomatis. PMID- 27006462 TI - Changes in the Eye Microbiota Associated with Contact Lens Wearing. AB - Wearing contact lenses has been identified as a risk factor for the development of eye conditions such as giant papillary conjunctivitis and keratitis. We hypothesized that wearing contact lenses is associated with changes in the ocular microbiota. We compared the bacterial communities of the conjunctiva and skin under the eye from 58 subjects and analyzed samples from 20 subjects (9 lens wearers and 11 non-lens wearers) taken at 3 time points using a 16S rRNA gene based sequencing technique (V4 region; Illumina MiSeq). We found that using anesthetic eye drops before sampling decreases the detected ocular microbiota diversity. Compared to those from non-lens wearers, dry conjunctival swabs from lens wearers had more variable and skin-like bacterial community structures (UniFrac;P value = <0.001), with higher abundances of Methylobacterium,Lactobacillus,Acinetobacter, andPseudomonasand lower abundances of Haemophilus,Streptococcus,Staphylococcus, and Corynebacterium(linear discriminant analysis [LDA] score = >3.0). The results indicate that wearing contact lenses alters the microbial structure of the ocular conjunctiva, making it more similar to that of the skin microbiota. Further research is needed to determine whether the microbiome structure provides less protection from ocular infections. IMPORTANCE: As in other body sites (i.e., the gut, skin, and mouth), the eye has a normal community of bacteria which are expected to confer resistance that provides protection from invaders. However, the eye microbiome has been largely neglected and is relevant to eye health and understanding eye diseases and to discovery of its functions. This report of a baseline study shows differences in the eye microbiome of contact lens wearers in relation to those of non-lens wearers and has the potential to help future studies explore novel insights into a possible role of the microbiome in the increased risk for eye infections in contact lens wearers. PMID- 27006463 TI - Role of Multicellular Aggregates in Biofilm Formation. AB - In traditional models ofin vitrobiofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development ofPseudomonas aeruginosabiofilms. We find that the relative fitness of aggregates depends markedly on the density of surrounding single cells, i.e., the level of competition for growth resources. When competition between aggregates and single cells is low, an aggregate has a growth disadvantage because the aggregate interior has poor access to growth resources. However, if competition is high, aggregates exhibit higher fitness, because extending vertically above the surface gives cells at the top of aggregates better access to growth resources. Other advantages of seeding by aggregates, such as earlier switching to a biofilm-like phenotype and enhanced resilience toward antibiotics and immune response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation. IMPORTANCE: During the past decades, there has been a consensus around the model of development of a biofilm, involving attachment of single planktonic bacterial cells to a surface and the subsequent development of a mature biofilm. This study presents results that call for a modification of this rigorous model. We show how free floating biofilm aggregates can have a profound local effect on biofilm development when attaching to a surface. Our findings show that an aggregate landing on a surface will eventually outcompete the biofilm population arising from single cells attached around the aggregate and dominate the local biofilm development. These results point to a regime where preformed biofilm aggregates may have a fitness advantage over planktonic cells when it comes to accessing nutrients. Our findings add to the increasingly prominent comprehension that biofilm lifestyle is the default for bacteria and that planktonic single cells may be only a transition state at the most. PMID- 27006464 TI - Cryo-electron Microscopy Structures of Chimeric Hemagglutinin Displayed on a Universal Influenza Vaccine Candidate. AB - Influenza viruses expressing chimeric hemagglutinins (HAs) are important tools in the quest for a universal vaccine. Using cryo-electron tomography, we have determined the structures of a chimeric HA variant that comprises an H1 stalk and an H5 globular head domain (cH5/1 HA) in native and antibody-bound states. We show that cH5/1 HA is structurally different from native HA, displaying a 60 degrees rotation between the stalk and head groups, leading to a novel and unexpected "open" arrangement of HA trimers. cH5/1N1 viruses also display higher glycoprotein density than pH1N1 or H5N1 viruses, but despite these differences, antibodies that target either the stalk or head domains of hemagglutinins still bind to cH5/1 HA with the same consequences as those observed with native H1 or H5 HA. Our results show that a large range of structural plasticity can be tolerated in the chimeric spike scaffold without disrupting structural and geometric aspects of antibody binding. IMPORTANCE: Chimeric hemagglutinin proteins are set to undergo human clinical trials as a universal influenza vaccine candidate, yet no structural information for these proteins is available. Using cryo-electron tomography, we report the first three-dimensional (3D) visualization of chimeric hemagglutinin proteins displayed on the surface of the influenza virus. We show that, unexpectedly, the chimeric hemagglutinin structure differs from those of naturally occurring hemagglutinins by displaying a more open head domain and a dramatically twisted head/stalk arrangement. Despite this unusual spatial relationship between head and stalk regions, virus preparations expressing the chimeric hemagglutinin are fully infectious and display a high glycoprotein density, which likely helps induction of a broadly protective immune response. PMID- 27006465 TI - Interaction between Simian Virus 40 Major Capsid Protein VP1 and Cell Surface Ganglioside GM1 Triggers Vacuole Formation. AB - Simian virus 40 (SV40), a polyomavirus that has served as an important model to understand many aspects of biology, induces dramatic cytoplasmic vacuolization late during productive infection of monkey host cells. Although this activity led to the discovery of the virus in 1960, the mechanism of vacuolization is still not known. Pentamers of the major SV40 capsid protein VP1 bind to the ganglioside GM1, which serves as the cellular receptor for the virus. In this report, we show that binding of VP1 to cell surface GM1 plays a key role in SV40 infection induced vacuolization. We previously showed that SV40 VP1 mutants defective for GM1 binding fail to induce vacuolization, even though they replicate efficiently. Here, we show that interfering with GM1-VP1 binding by knockdown of GM1 after infection is established abrogates vacuolization by wild-type SV40. Vacuole formation during permissive infection requires efficient virus release, and conditioned medium harvested late during SV40 infection rapidly induces vacuoles in a VP1- and GM1-dependent fashion. Furthermore, vacuolization can also be induced by a nonreplicating SV40 pseudovirus in a GM1-dependent manner, and a mutation in BK pseudovirus VP1 that generates GM1 binding confers vacuole inducing activity. Vacuolization can also be triggered by purified pentamers of wild-type SV40 VP1, but not by GM1 binding-defective pentamers or by intracellular expression of VP1. These results demonstrate that SV40 infection induced vacuolization is caused by the binding of released progeny viruses to GM1, thereby identifying the molecular trigger for the activity that led to the discovery of SV40. IMPORTANCE: The DNA tumor virus SV40 was discovered more than a half century ago as a contaminant of poliovirus vaccine stocks, because it caused dramatic cytoplasmic vacuolization of permissive host cells. Although SV40 played a historically important role in the development of molecular and cellular biology, restriction mapping, molecular cloning, and whole-genome sequencing, the basis of this vacuolization phenotype was unknown. Here, we show that SV40 induced vacuolization is triggered by the binding of the major viral capsid protein, VP1, to a cell surface ganglioside receptor, GM1. No other viral proteins or virus replication is required for vacuole formation. Other polyomaviruses utilize different ganglioside receptors, but they do not induce vacuolization. This work identifies the molecular trigger for the phenotype that led to the discovery of this important virus and provides the first molecular insight into an unusual and enigmatic cytopathic effect due to virus infection. PMID- 27006466 TI - Delivery of RANKL-Binding Peptide OP3-4 Promotes BMP-2-Induced Maxillary Bone Regeneration. AB - Although bone morphogenetic protein 2 (BMP-2) is known to stimulate osteogenesis, there is evidence that high doses of BMP-2 can lead to side effects, including inflammation and carcinogenesis. The supplementation of other bone-augmenting agents is considered helpful in preventing such side effects by reducing the amount of BMP-2 required to obtain a sufficient amount of bone. We recently showed that a receptor activator of nuclear factor kappaB ligand (RANKL)-binding peptide promotes osteoblast differentiation. In the present study, we aimed to investigate whether OP3-4, a RANKL-binding peptide, promotes BMP-2-induced bone formation in the murine maxilla using an injectable gelatin hydrogel (GH) carrier. A GH carrier containing OP3-4 with BMP-2 was subperiosteally injected into the murine maxillary right diastema between the incisor and the first molar. The mice were sacrificed 28 d after the injections. The local bone formation in the OP3-4-BMP-2-injected group was analyzed in comparison to the carrier injected, BMP-2-injected, and control-peptide-BMP-2-injected groups. The GH carrier containing OP3-4 with BMP-2 enlarged the radio-opaque area and increased the bone mineral content and density in the radiological analyses in comparison to the other experimental groups. Interestingly, fluorescence-based histological analyses revealed that the mineralization had started from the outside, then proceeded inward, suggesting that the size of the newly formed bone had already been set before calcification started and that the effects of OP3-4 might be involved in accelerating the early steps of osteogenesis. Actually, OP3-4 enhanced the BMP-2-induced 5-bromo-2'-deoxyuridine (BrdU)-positive cell numbers at the injected site on day 7 and the expression of Runx2 and Col1a1, which are early osteogenic cell markers, on day 10 after the subperiosteal injections. In summary, we demonstrated, for the first time, that the application of OP3-4 by subperiosteal injection promoted BMP-2-induced bone formation, which could lead to the development of an easy and noninvasive means of promoting alveolar ridge formation. PMID- 27006467 TI - Evaluation of semen collected from commercial rams by electro-ejaculation. PMID- 27006468 TI - C-terminal truncated hepatitis B virus X protein promotes hepatocellular carcinogenesis through induction of cancer and stem cell-like properties. AB - Tumor relapse after chemotherapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive initial treatment. Chronic infection with hepatitis B virus (HBV) has long been linked to the development of HCC. Upon infection, random HBV genome integration can lead to truncation of hepatitis B virus X (HBx) protein at the C-terminus. The resulting C-terminal-truncated HBx (HBx-DeltaC) was previously shown to confer enhanced invasiveness and diminished apoptotic response in HCC cells. Here, we found HBx-DeltaC to promote the appearance of a CD133 liver CSC subset and confer cancer and stem cell-like features in HCC. HBx-DeltaC was exclusively detected in HCC cell lines that were raised from patients presented with a HBV background with concomitant CD133 expression. Stable overexpression of the naturally occurring HBx-DeltaC mutants, HBx-Delta14 or HBx-Delta35, in HCC cells Huh7 and immortalized normal liver cells MIHA resulted in a significant increase in the cells ability to self-renew, resist chemotherapy and targeted therapy, migrate and induce angiogenesis. MIHA cells with the mutants stably overexpressed also resulted in the induction of CD133, mediated through STAT3 activation. RNA sequencing profiling of MIHA cells with or without HBx-DeltaC mutants stably overexpressed identified altered FXR activation. This, together with rescue experiments using a selective FXR inhibitor suggested that C-terminal truncated HBx can mediate cancer stemness via FXR activation. Collectively, we find C terminal truncated HBx mutants to confer cancer and stem cell-like features in vitro and to play an important role in driving tumor relapse in HCC. PMID- 27006469 TI - Discovery and characterization of Isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to TRAIL in cancer cells. AB - We characterized the brominated alkaloid Isofistularin-3 (Iso-3), from the marine sponge Aplysina aerophoba, as a new DNA methyltransferase (DNMT)1 inhibitor. Docking analysis confirmed our in vitro DNMT inhibition data and revealed binding of Iso-3 within the DNA binding site of DNMT1. Subsequent increased expression of tumor suppressor gene aryl hydrocarbon receptor (AHR) could be correlated to decreased methylation of CpG sites within the essential Sp1 regulatory region of its promoter. Iso-3 induced growth arrest of cancer cells in G0/G1 concomitant with increased p21 and p27 expression and reduced cyclin E1, PCNA and c-myc levels. Reduced proliferation was accompanied by morphological changes typical of autophagy revealed by fluorescent and transmission electron microscopy and validated by LC3I-II conversion. Furthermore, Iso-3 strongly synergized with tumor-necrosis-factor related apoptosis inducing ligand (TRAIL) in RAJI [combination index (CI) = 0.22] and U-937 cells (CI = 0.21) and increased TRAIL induced apoptosis via a mechanism involving reduction of survivin expression but not of Bcl-2 family proteins nor X-linked inhibitor of apoptosis protein (XIAP). Iso-3 treatment decreased FLIPL expression and triggered activation of endoplasmatic reticulum (ER) stress with increased GRP78 expression, eventually inducing TRAIL receptor death receptor (DR)5 surface expression. Importantly, as a potential candidate for further anticancer drug development, Iso-3 reduced the viability, colony and in vivo tumor forming potential without affecting the viability of PBMCs from healthy donors or zebrafish development. PMID- 27006470 TI - An evolutionarily conserved negative feedback mechanism in the Hippo pathway reflects functional difference between LATS1 and LATS2. AB - The Hippo pathway represses YAP oncoprotein activity through phosphorylation by LATS kinases. Although variety of upstream components has been found to participate in the Hippo pathway, the existence and function of negative feedback has remained uncertain. We found that activated YAP, together with TEAD transcription factors, directly induces transcription of LATS2, but not LATS1, to form a negative feedback loop. We also observed increased mRNA levels of Hippo upstream components upon YAP activation. To reveal the physiological role of this negative feedback regulation, we deleted Lats2 or Lats1 in the liver-specific Sav1-knockout mouse model which develops a YAP-induced tumor. Additional deletion of Lats2 severely enhanced YAP-induced tumorigenic phenotypes in a liver specific Sav1 knock-out mouse model while additional deletion of Lats1 mildly affected the phenotype. Only Sav1 and Lats2 double knock-down cells formed larger colonies in soft agar assay, thereby recapitulating accelerated tumorigenesis seen in vivo. Importantly, this negative feedback is evolutionarily conserved, as Drosophila Yorkie (YAP ortholog) induces transcription of Warts (LATS2 ortholog) with Scalloped (TEAD ortholog). Collectively, we demonstrated the existence and function of an evolutionarily conserved negative feedback mechanism in the Hippo pathway, as well as the functional difference between LATS1 and LATS2 in regulation of YAP. PMID- 27006471 TI - An individualized prognostic signature and multi-omics distinction for early stage hepatocellular carcinoma patients with surgical resection. AB - Previously reported prognostic signatures for predicting the prognoses of postsurgical hepatocellular carcinoma (HCC) patients are commonly based on predefined risk scores, which are hardly applicable to samples measured by different laboratories. To solve this problem, using gene expression profiles of 170 stage I/II HCC samples, we identified a prognostic signature consisting of 20 gene pairs whose within-sample relative expression orderings (REOs) could robustly predict the disease-free survival and overall survival of HCC patients. This REOs-based prognostic signature was validated in two independent datasets. Functional enrichment analysis showed that the patients with high-risk of recurrence were characterized by the activations of pathways related to cell proliferation and tumor microenvironment, whereas the low-risk patients were characterized by the activations of various metabolism pathways. We further investigated the distinct epigenomic and genomic characteristics of the two prognostic groups using The Cancer Genome Atlas samples with multi-omics data. Epigenetic analysis showed that the transcriptional differences between the two prognostic groups were significantly concordant with DNA methylation alternations. The signaling network analysis identified several key genes (e.g. TP53, MYC) with epigenomic or genomic alternations driving poor prognoses of HCC patients. These results help us understand the multi-omics mechanisms determining the outcomes of HCC patients. PMID- 27006473 TI - Neurocognitive and Academic Outcomes at Age 10 Years of Extremely Preterm Newborns. AB - BACKGROUND AND OBJECTIVE: Despite reductions in mortality and morbidity among children born extremely preterm, they remain at high risk of neurocognitive deficits, with up to 40% having significant cognitive deficits at school age. We assessed the rate of neurocognitive impairment in a contemporary US cohort of 873 children aged 10 years who were born <28 weeks' gestation. METHODS: The families of 889 of 966 (92%) children enrolled from 2002 to 2004 at 14 sites in 5 states returned at age 10 years for a comprehensive assessment of IQ, language, attention, executive function, processing speed, visual perception, visual-motor function, and academic achievement. RESULTS: A total of 873 children were assessed with well-validated tests of cognitive and academic function. Distributions of test scores were consistently and markedly shifted below normative expectation, with one-third to two-thirds of children performing >1 SD below age expectation. The most extreme downward shifts were on measures of executive control and processing speed. Multivariate analyses, adjusted for socioeconomic status, growth restriction, and other potential confounders, revealed that the risk of poor outcome was highest at the lowest gestational age across all 18 measures. CONCLUSIONS: More than half of our extremely preterm cohort exhibited moderate or severe neurocognitive deficits at age 10 years, with the most extensive impairments found among those born at the lowest gestational age. Children born extremely preterm continue to be at significant risk of persistent impairments in neurocognitive function and academic achievement, underscoring the need for monitoring and remediating such outcomes beginning in early childhood. PMID- 27006475 TI - Current Workforce of General Pediatricians in the United States. AB - BACKGROUND AND OBJECTIVES: A near vacuum exists for credible information regarding specialty-specific demography, including gender, years since training completion, current employer, academic affiliation, and hours worked in specific tasks. Understanding the current status and changes to the medical workforce and its work patterns is essential to assessing whether the supply and distribution meets the needs of patients, institutions, society, and educational programs. METHODS: A self-administered electronic survey sent to all pediatricians at the time of their enrollment in the Maintenance of Certification program in 2013 2014. The survey focused on exploring trends associated with career choice, career paths, time spent in professional activities, and current practice characteristics. Logistic regression and chi(2) analyses were conducted. RESULTS: The response rate was 87.2% (N = 15 351). Of those who completed the survey, 9253 (64%) self-identified as general pediatricians. An increased likelihood of working part-time was seen among women (odds ratio [OR]: 12.21), those without an academic appointment (OR: 1.32), and those not working in a private/independent practice (OR: 1.15). Overall, 89% (n = 8214) of respondents stated that their current allocation of professional time was approximately what they wanted. Those more likely to be involved in quality improvement in the past year did not work in independent/private practices (OR: 1.78) and worked full-time (OR: 1.16). CONCLUSIONS: Understanding the current nature of the pediatric workforce is a first step in providing data to guide future workforce planning and the training experiences required to maintain and shape the workforce to meet the current and future needs of children. PMID- 27006474 TI - Maternal Iodine Exposure: A Case of Fetal Goiter and Neonatal Hearing Loss. AB - A 27-year-old gravid 1 at 27 weeks 6 days with a history of hypothyroidism had an ultrasound that demonstrated a 3.9 * 3.2 * 3.3-cm well-circumscribed anterior neck mass, an extended fetal head, and polyhydramnios. Further characterization by magnetic resonance imaging (MRI) showed a fetal goiter. During her evaluation for the underlying cause of the fetal goiter, the patient revealed she was taking nutritional iodine supplements for treatment of her hypothyroidism. She was ingesting 62.5 times the recommended amount of daily iodine in pregnancy. The excessive iodine consumption caused suppression of the fetal thyroid hormone production, resulting in hypothyroidism and goiter formation. After the iodine supplement was discontinued, the fetal goiter decreased in size. At delivery, the airway was not compromised. The infant was found to have reversible hypothyroidism and bilateral hearing loss postnatally. This case illustrates the importance of examining for iatrogenic causes for fetal anomalies, especially in unregulated nutritional supplements. PMID- 27006472 TI - Targeting the epigenetic readers in Ewing sarcoma inhibits the oncogenic transcription factor EWS/Fli1. AB - Ewing Sarcoma is a rare bone and soft tissue malignancy affecting children and young adults. Chromosomal translocations in this cancer produce fusion oncogenes as characteristic molecular signatures of the disease. The most common case is the translocation t (11; 22) (q24;q12) which yields the EWS-Fli1 chimeric transcription factor. Finding a way to directly target EWS-Fli1 remains a central therapeutic approach to eradicate this aggressive cancer. Here we demonstrate that treating Ewing Sarcoma cells with JQ1(+), a BET bromodomain inhibitor, represses directly EWS-Fli1 transcription as well as its transcriptional program. Moreover, the Chromatin Immuno Precipitation experiments demonstrate for the first time that these results are a consequence of the depletion of BRD4, one of the BET bromodomains protein from the EWS-Fli1 promoter. In vitro, JQ1(+) treatment reduces the cell viability, impairs the cell clonogenic and the migratory abilities, and induces a G1-phase blockage as well as a time- and a dose-dependent apoptosis. Furthermore, in our in vivo model, we observed a tumor burden delay, an inhibition of the global vascularization and an increase of the mice overall survival. Taken together, our data indicate that inhibiting the BET bromodomains interferes with EWS-FLi1 transcription and could be a promising strategy in the Ewing tumors context. PMID- 27006477 TI - Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. AB - Cord blood stem cells are an attractive starting source for the production of red blood cells in vitro for therapy because of additional expansion potential compared with adult peripheral blood progenitors and cord blood banks usually being more representative of national populations than blood donors. Consequently, it is important to establish how similar cord RBCs are to adult cells. In this study, we used multiplex tandem mass tag labeling combined with nano-LC-MS/MS to compare the proteome of adult and cord RBCs and reticulocytes. 2838 unique proteins were identified, providing the most comprehensive compendium of RBC proteins to date. Using stringent criteria, 1674 proteins were quantified, and only a small number differed in amount between adult and cord RBC. We focused on proteins critical for RBC function. Of these, only the expected differences in globin subunits, along with higher levels of carbonic anhydrase 1 and 2 and aquaporin-1 in adult RBCs would be expected to have a phenotypic effect since they are associated with the differences in gaseous exchange between adults and neonates. Since the RBC and reticulocyte samples used were autologous, we catalogue the change in proteome following reticulocyte maturation. The majority of proteins (>60% of the 1671 quantified) reduced in abundance between 2- and 100 fold following maturation. However, ~5% were at a higher level in RBCs, localized almost exclusively to cell membranes, in keeping with the known clearance of intracellular recycling pools during reticulocyte maturation. Overall, these data suggest that, with respect to the proteome, there is no barrier to the use of cord progenitors for the in vitro generation of RBCs for transfusion to adults other than the expression of fetal, not adult, hemoglobin. PMID- 27006476 TI - Assembly Dynamics and Stoichiometry of the Apoptosis Signal-regulating Kinase (ASK) Signalosome in Response to Electrophile Stress. AB - Apoptosis signal-regulating kinase 1 (ASK1) is a key sensor kinase in the mitogen activated protein kinase pathway that transduces cellular responses to oxidants and electrophiles. ASK1 is regulated by a large, dynamic multiprotein signalosome complex, potentially including over 90 reported ASK1-interacting proteins. We employed both shotgun and targeted mass spectrometry assays to catalogue the ASK1 protein-protein interactions in HEK-293 cells treated with the prototypical lipid electrophile 4-hydroxy-2-nonenal (HNE). Using both epitope-tagged overexpression and endogenous expression cell systems, we verified most of the previously reported ASK1 protein-protein interactions and identified 14 proteins that exhibited dynamic shifts in association with ASK1 in response to HNE stress. We used precise stable isotope dilution assays to quantify protein stoichiometry in the ASK signalosome complex and identified ASK2 at a 1:1 stoichiometric ratio with ASK1 and 14-3-3 proteins (YWHAQ, YWHAB, YWHAH, and YWHAE) collectively at a 0.5:1 ratio with ASK1 as the main components. Several other proteins, including ASK3, PARK7, PRDX1, and USP9X were detected with stoichiometries of 0.1:1 or less. These data support an ASK signalosome comprising a multimeric core complex of ASK1, ASK2, and 14-3-3 proteins, which dynamically engages other binding partners needed to mediate diverse stress-response signaling events. This study further demonstrates the value of combining global and targeted MS approaches to interrogate multiprotein complex composition and dynamics. PMID- 27006478 TI - Evolution of Mitral Valve Prolapse: Insights From the Framingham Heart Study. AB - BACKGROUND: Longitudinal studies of mitral valve prolapse (MVP) progression among unselected individuals in the community, including those with nondiagnostic MVP morphologies (NDMs), are lacking. METHODS AND RESULTS: We measured longitudinal changes in annular diameter, leaflet displacement, thickness, anterior/posterior leaflet projections onto the annulus, coaptation height, and mitral regurgitation jet height in 261 Framingham Offspring participants at examination 5 who had available follow-up imaging 3 to 16 years later. Study participants included MVP (n=63); NDMs, minimal systolic displacement (n=50) and the abnormal anterior coaptation phenotype (n=10, with coaptation height >40% of the annulus similar to posterior MVP); plus 138 healthy referents without MVP or NDMs. At follow-up, individuals with MVP (52% women, 57+/-11 years) had greater increases of leaflet displacement, thickness, and jet height than referents (all P<0.05). Eleven participants with MVP (17%) had moderate or more severe mitral regurgitation (jet height >=5 mm) and 5 others (8%) underwent mitral valve repair. Of the individuals with NDM, 8 (80%) participants with abnormal anterior coaptation progressed to posterior MVP; 17 (34%) subjects with minimal systolic displacement were reclassified as either posterior MVP (12) or abnormal anterior coaptation (5). In comparison with the 33 participants with minimal systolic displacement who did not progress, the 17 who progressed had greater leaflet displacement, thickness, coaptation height, and mitral regurgitation jet height (all P<0.05). CONCLUSIONS: NDM may evolve into MVP, highlighting the clinical significance of mild MVP expression. MVP progresses to significant mitral regurgitation over a period of 3 to 16 years in one-fourth of individuals in the community. Changes in mitral leaflet morphology are associated with both NDM and MVP progression. PMID- 27006479 TI - Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts. AB - BACKGROUND: In prospective studies, the relationship of self-reported consumption of dairy foods with risk of diabetes mellitus is inconsistent. Few studies have assessed dairy fat, using circulating biomarkers, and incident diabetes mellitus. We tested the hypothesis that circulating fatty acid biomarkers of dairy fat, 15:0, 17:0, and t-16:1n-7, are associated with lower incident diabetes mellitus. METHODS AND RESULTS: Among 3333 adults aged 30 to 75 years and free of prevalent diabetes mellitus at baseline, total plasma and erythrocyte fatty acids were measured in blood collected in 1989 to 1990 (Nurses' Health Study) and 1993 to 1994 (Health Professionals Follow-Up Study). Incident diabetes mellitus through 2010 was confirmed by a validated supplementary questionnaire based on symptoms, diagnostic tests, and medications. Risk was assessed by using Cox proportional hazards, with cohort findings combined by meta-analysis. During mean+/-standard deviation follow-up of 15.2+/-5.6 years, 277 new cases of diabetes mellitus were diagnosed. In pooled multivariate analyses adjusting for demographics, metabolic risk factors, lifestyle, diet, and other circulating fatty acids, individuals with higher plasma 15:0 had a 44% lower risk of diabetes mellitus (quartiles 4 versus 1, hazard ratio, 0.56; 95% confidence interval, 0.37-0.86; P-trend=0.01); higher plasma 17:0, 43% lower risk (hazard ratio, 0.57; 95% confidence interval, 0.39-0.83; P-trend=0.01); and higher t-16:1n-7, 52% lower risk (hazard ratio, 0.48; 95% confidence interval, 0.33-0.70; P-trend <0.001). Findings were similar for erythrocyte 15:0, 17:0, and t-16:1n-7, although with broader confidence intervals that only achieved statistical significance for 17:0. CONCLUSIONS: In 2 prospective cohorts, higher plasma dairy fatty acid concentrations were associated with lower incident diabetes mellitus. Results were similar for erythrocyte 17:0. Our findings highlight the need to better understand the potential health effects of dairy fat, and the dietary and metabolic determinants of these fatty acids. PMID- 27006480 TI - Trends in Mortality From Ischemic Heart Disease and Cerebrovascular Disease in Europe: 1980 to 2009. AB - BACKGROUND: Trends in cardiovascular mortality across Europe demonstrate significant geographical variation, and an understanding of these trends has a central role in global public health. METHODS AND RESULTS: Ischemic heart disease and cerebrovascular disease age-standardized death rates (as per International Classification of Diseases, ninth and tenth revisions) were collated from the World Health Organization mortality database for member states of the European Union. Trends were characterized by using Joinpoint regression analysis. An overall trend for reduction in ischemic heart disease mortality was observed, most pronounced in Western Europe (>60% for the Netherlands, United Kingdom, and Ireland) for both sexes from 1980 to 2009. Eastern European states, Romania, Croatia, and Slovakia, had modest mortality reductions. Most recently (2009), Lithuania had the highest mortality for males and females (318.1/100 000 and 166.1/100 000, respectively), followed by Latvia and Slovakia. France had the lowest mortality: 39.8/100 000 for males and 14.7/100 000 for females. Analysis of cerebrovascular disease mortality revealed that Austria had the largest reduction for both sexes (76.8% males, 76.5% females) from 1980 to 2009. The smallest improvement over this period was seen in Lithuania, Poland, and Cyprus ( 5% to +20% approximately). France has the lowest present-day cerebrovascular disease mortality for both males and females (23.9/100 000 and 17.3/100 000, respectively). CONCLUSIONS: There is a growing disparity in cardiovascular mortality between Western and Eastern Europe, for which diverse explanations are discussed. The need for population-wide health promotion and primary prevention policies is emphasized. PMID- 27006482 TI - Carbon monoxide poisoning and risk for venous thromboembolism. PMID- 27006481 TI - Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension. AB - BACKGROUND: The mechanisms of right ventricular (RV) failure in pulmonary arterial hypertension (PAH) are poorly understood. Abnormalities in fatty acid (FA) metabolism have been described in experimental models of PAH, but systemic and myocardial FA metabolism has not been studied in human PAH. METHODS AND RESULTS: We used human blood, RV tissue, and noninvasive imaging to characterize multiple steps in the FA metabolic pathway in PAH subjects and controls. Circulating free FAs and long-chain acylcarnitines were elevated in PAH patients versus controls. Human RV long-chain FAs were increased and long-chain acylcarnitines were markedly reduced in PAH versus controls. With the use of proton magnetic resonance spectroscopy, in vivo myocardial triglyceride content was elevated in human PAH versus controls (1.4+/-1.3% triglyceride versus 0.22+/ 0.11% triglyceride, P=0.02). Ceramide, a mediator of lipotoxicity, was increased in PAH RVs versus controls. Using an animal model of heritable PAH, we demonstrated reduced FA oxidation via failure of palmitoylcarnitine to stimulate oxygen consumption in the PAH RV. CONCLUSIONS: Abnormalities in FA metabolism can be detected in the blood and myocardium in human PAH and are associated with in vivo cardiac steatosis and lipotoxicity. Murine data suggest that lipotoxicity may arise from reduction in FA oxidation. PMID- 27006483 TI - Plastid ribosomal protein S5 is involved in photosynthesis, plant development, and cold stress tolerance in Arabidopsis. AB - Plastid ribosomal proteins are essential components of protein synthesis machinery and have diverse roles in plant growth and development. Mutations in plastid ribosomal proteins lead to a range of developmental phenotypes in plants. However, how they regulate these processes is not fully understood, and the functions of some individual plastid ribosomal proteins remain unknown. To identify genes responsible for chloroplast development, we isolated and characterized a mutant that exhibited pale yellow inner leaves with a reduced growth rate in Arabidopsis. The mutant (rps5) contained a missense mutation of plastid ribosomal protein S5 (RPS5), which caused a dramatically reduced abundance of chloroplast 16S rRNA and seriously impaired 16S rRNA processing to affect ribosome function and plastid translation. Comparative proteomic analysis revealed that the rps5 mutation suppressed the expression of a large number of core components involved in photosystems I and II as well as many plastid ribosomal proteins. Unexpectedly, a number of proteins associated with cold stress responses were greatly decreased in rps5, and overexpression of the plastid RPS5 improved plant cold stress tolerance. Our results indicate that RPS5 is an important constituent of the plastid 30S subunit and affects proteins involved in photosynthesis and cold stress responses to mediate plant growth and development. PMID- 27006484 TI - The analysis of Gene Regulatory Networks in plant evo-devo. AB - We provide an overview of methods and workflows that can be used to investigate the topologies of Gene Regulatory Networks (GRNs) in the context of plant evolutionary-developmental (evo-devo) biology. Many of the species that occupy key positions in plant phylogeny are poorly adapted as laboratory models and so we focus here on techniques that can be efficiently applied to both model and non model species of interest to plant evo-devo. We outline methods that can be used to describe gene expression patterns and also to elucidate the transcriptional, post-transcriptional, and epigenetic regulatory mechanisms underlying these patterns, in any plant species with a sequenced genome. We furthermore describe how the technique of Protein Resurrection can be used to confirm inferences on ancestral GRNs and also to provide otherwise-inaccessible points of reference in evolutionary histories by exploiting paralogues generated in gene and whole genome duplication events. Finally, we argue for the better integration of molecular data with information from paleobotanical, paleoecological, and paleogeographical studies to provide the fullest possible picture of the processes that have shaped the evolution of plant development. PMID- 27006485 TI - Interactions between Brassinosteroids and Gibberellins: Synthesis or Signaling? PMID- 27006486 TI - Reply: Interaction between Brassinosteroids and Gibberellins: Synthesis or Signaling? In Arabidopsis, Both! PMID- 27006487 TI - Reply: Brassinosteroid Regulates Gibberellin Synthesis to Promote Cell Elongation in Rice: Critical Comments on Ross and Quittenden's Letter. PMID- 27006488 TI - Sterol Methyl Oxidases Affect Embryo Development via Auxin-Associated Mechanisms. AB - Sterols are essential molecules for multiple biological processes, including embryogenesis, cell elongation, and endocytosis. The plant sterol biosynthetic pathway is unique in the involvement of two distinct sterol 4alpha-methyl oxidase (SMO) families, SMO1 and SMO2, which contain three and two isoforms, respectively, and are involved in sequential removal of the two methyl groups at C-4. In this study, we characterized the biological functions of members of the SMO2 gene family. SMO2-1 was strongly expressed in most tissues during Arabidopsis (Arabidopsis thaliana) development, whereas SMO2-2 showed a more specific expression pattern. Although single smo2 mutants displayed no obvious phenotype, the smo2-1 smo2-2 double mutant was embryonic lethal, and the smo2-1 smo2-2/+ mutant was dwarf, whereas the smo2-1/+ smo2-2 mutant exhibited a moderate phenotype. The phenotypes of the smo2 mutants resembled those of auxin defective mutants. Indeed, the expression of DR5rev:GFP, an auxin-responsive reporter, was reduced and abnormal in smo2-1 smo2-2 embryos. Furthermore, the expression and subcellular localization of the PIN1 auxin efflux facilitator also were altered. Consistent with these observations, either the exogenous application of auxin or endogenous auxin overproduction (YUCCA9 overexpression) partially rescued the smo2-1 smo2-2 embryonic lethality. Surprisingly, the dwarf phenotype of smo2-1 smo2-2/+ was completely rescued by YUCCA9 overexpression. Gas chromatography-mass spectrometry analysis revealed a substantial accumulation of 4alpha-methylsterols, substrates of SMO2, in smo2 heterozygous double mutants. Together, our data suggest that SMO2s are important for correct sterol composition and function partially through effects on auxin accumulation, auxin response, and PIN1 expression to regulate Arabidopsis embryogenesis and postembryonic development. PMID- 27006489 TI - Long-Distance Transport of Thiamine (Vitamin B1) Is Concomitant with That of Polyamines. AB - Thiamine (vitamin B1) is ubiquitous and essential for cell energy supply in all organisms as a vital metabolic cofactor, known for over a century. In plants, it is established that biosynthesis de novo is taking place predominantly in green tissues and is furthermore limited to plastids. Therefore, transport mechanisms are required to mediate the movement of this polar metabolite from source to sink tissue to activate key enzymes in cellular energy generating pathways but are currently unknown. Similar to thiamine, polyamines are an essential set of charged molecules required for diverse aspects of growth and development, the homeostasis of which necessitates long-distance transport processes that have remained elusive. Here, a yeast-based screen allowed us to identify Arabidopsis (Arabidopsis thaliana) PUT3 as a thiamine transporter. A combination of biochemical, physiological, and genetic approaches permitted us to show that PUT3 mediates phloem transport of both thiamine and polyamines. Loss of function of PUT3 demonstrated that the tissue distribution of these metabolites is altered with growth and developmental consequences. The pivotal role of PUT3 mediated thiamine and polyamine homeostasis in plants, and its importance for plant fitness is revealed through these findings. PMID- 27006490 TI - Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer-Combined Analysis of the PORTEC Cohorts. AB - PURPOSE: Recommendations for adjuvant treatment for women with early-stage endometrial carcinoma are based on clinicopathologic features. Comprehensive genomic characterization defined four subgroups: p53-mutant, microsatellite instability (MSI), POLE-mutant, and no specific molecular profile (NSMP). We aimed to confirm the prognostic capacity of these subgroups in large randomized trial populations, investigate potential other prognostic classifiers, and integrate these into an integrated molecular risk assessment guiding adjuvant therapy. EXPERIMENTAL DESIGN: Analysis of MSI, hotspot mutations in 14 genes including POLE, protein expression of p53, ARID1a, beta-catenin, L1CAM, PTEN, ER, and PR was undertaken on 947 available early-stage endometrioid endometrial carcinomas from the PORTEC-1 and -2 trials, mostly high-intermediate risk (n = 614). Prognostic value was determined using univariable and multivariable Cox proportional hazard models. AUCs of different risk stratification models were compared. RESULTS: Molecular analyses were feasible in >96% of the patients and confirmed the four molecular subgroups: p53-mutant (9%), MSI (26%), POLE-mutant (6%), and NSMP (59%). Integration of prognostic molecular alterations with established clinicopathologic factors resulted in a stronger model with improved risk prognostication. Approximately 15% of high-intermediate risk patients had unfavorable features (substantial lymphovascular space invasion, p53-mutant, and/or >10% L1CAM), 50% favorable features (POLE-mutant, NSMP being microsatellite stable, and CTNNB1 wild-type), and 35% intermediate features (MSI or CTNNB1-mutant). CONCLUSIONS: Integrating clinicopathologic and molecular factors improves the risk assessment of patients with early-stage endometrial carcinoma. Assessment of this integrated risk profile is feasible in daily practice, and holds promise to reduce both overtreatment and undertreatment. Clin Cancer Res; 22(16); 4215-24. (c)2016 AACR. PMID- 27006492 TI - Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. AB - PURPOSE: Adoptive cell transfer therapy (ACT) based on autologous tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen. EXPERIMENTAL DESIGN: Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age < 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625). RESULTS: Classical IL2 related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment. CONCLUSIONS: TIL-ACT with a reduced IL2 decrescendo regimen results in long lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. (c)2016 AACR. PMID- 27006491 TI - Leukemic Stem Cell Quantification in Newly Diagnosed Patients With Chronic Myeloid Leukemia Predicts Response to Nilotinib Therapy. AB - PURPOSE: Leukemic stem cells (LSCs) may harbor important resistance to tyrosine kinase inhibitors in chronic myelogenous leukemia (CML). We identified Philadelphia chromosome (Ph)-positive CD34(+)CD38(-) bone marrow cells (here denoted LSCs) and addressed their response-predictive value in patients with CML (n = 48) subjected to nilotinib in the ENEST1st trial (NCT01061177). EXPERIMENTAL DESIGN: Two flow cytometry-based cell sorting methods were used with multiparameter-directed CD45- (MPFC) and BCR-ABL1 probe-linked (FISH) identification of Ph-positive cells, respectively. RESULTS: We observed a positive correlation between the proportion of LSCs at diagnosis and established prognostic markers (blast count, spleen size, Sokal score, and hemoglobin). Conversely, a high LSC burden predicted for an inferior molecular response at 3 (MPFC and FISH), 6 (MPFC), 9 (FISH), and 15 months (FISH). During nilotinib therapy, the proportion of LSCs decreased rapidly. At 3 months, a median of only 0.3% LSCs remained among CD34(+)CD38(-) cells, and in 33% of the patients the LSC clone was not detectable anymore (FISH). The response kinetics was similar in LSC fractions as it was in the progenitor and unseparated bone marrow cell fractions. CONCLUSIONS: The proportion of LSCs at diagnosis, as analyzed by two independent methodologies, reflects the biology of the disease and appeared as a prognostic and response-predictive marker in patients with CML subjected to first-line nilotinib therapy. Clin Cancer Res; 22(16); 4030-8. (c)2016 AACR. PMID- 27006493 TI - Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution. AB - PURPOSE: Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. EXPERIMENTAL DESIGN: We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. RESULTS: Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. CONCLUSIONS: The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. (c)2016 AACR. PMID- 27006494 TI - Disulfiram when Combined with Copper Enhances the Therapeutic Effects of Temozolomide for the Treatment of Glioblastoma. AB - PURPOSE: Glioblastoma is one of the most lethal cancers in humans, and with existing therapy, survival remains at 14.6 months. Current barriers to successful treatment include their infiltrative behavior, extensive tumor heterogeneity, and the presence of a stem-like population of cells, termed brain tumor-initiating cells (BTIC) that confer resistance to conventional therapies. EXPERIMENTAL DESIGN: To develop therapeutic strategies that target BTICs, we focused on a repurposing approach that explored already-marketed (clinically approved) drugs for therapeutic potential against patient-derived BTICs that encompass the genetic and phenotypic heterogeneity of glioblastoma observed clinically. RESULTS: Using a high-throughput in vitro drug screen, we found that montelukast, clioquinol, and disulfiram (DSF) were cytotoxic against a large panel of patient derived BTICs. Of these compounds, disulfiram, an off-patent drug previously used to treat alcoholism, in the presence of a copper supplement, showed low nanomolar efficacy in BTICs including those resistant to temozolomide and the highly infiltrative quiescent stem-like population. Low dose DSF-Cu significantly augmented temozolomide activity in vitro, and importantly, prolonged in vivo survival in patient-derived BTIC models established from both newly diagnosed and recurrent tumors. Moreover, we found that in addition to acting as a potent proteasome inhibitor, DSF-Cu functionally impairs DNA repair pathways and enhances the effects of DNA alkylating agents and radiation. These observations suggest that DSF-Cu inhibits proteasome activity and augments the therapeutic effects of DNA-damaging agents (temozolomide and radiation). CONCLUSIONS: DSF-Cu should be considered as an adjuvant therapy for the treatment of patients with glioblastoma in both newly diagnosed and recurrent settings. Clin Cancer Res; 22(15); 3860-75. (c)2016 AACR. PMID- 27006495 TI - Neoantigen: A Long March toward Cancer Immunotherapy. AB - Somatic mutations in cancer give rise to neoantigens. Technology revolutions in cancer genomics and immunology have made it possible to rapidly identify neoantigens for cancer vaccines. Leisegang and colleagues report that it is practical to rapidly identify neoantigens for adoptive T-cell therapy in a mouse tumor model. Clin Cancer Res; 22(11); 2602-4. (c)2016 AACRSee related article by Leisegang et al., p. 2734. PMID- 27006497 TI - Improving Outcomes in Patients Receiving Dialysis: The Peer Kidney Care Initiative. AB - The past decade has witnessed a marked reduction in mortality rates among patients receiving maintenance dialysis. However, the reasons for this welcome development are uncertain, and greater understanding is needed to translate advances in care into additional survival gains. To fill important knowledge gaps and to enable dialysis provider organizations to learn from one another, with the aim of advancing patient care, the Peer Kidney Care Initiative (Peer) was created in 2014 by the chief medical officers of 14 United States dialysis provider organizations and the Chronic Disease Research Group. Areas of particular clinical importance were targeted to help shape the public health agenda in CKD and ESRD. Peer focuses on the effect of geographic variation on outcomes, the implications of seasonality for morbidity and mortality, the clinical significance of understudied disorders affecting dialysis patients, and the debate about how best to monitor and evaluate progress in care. In the realm of geovariation, Peer has provided key observations on regional variation in the rates of ESRD incidence, hospitalization, and pre-ESRD care. Regarding seasonality, Peer has reported on variation in both infection-related and non infection-related hospitalizations, suggesting that ambient environmental conditions may affect a range of health outcomes in dialysis patients. Specific medical conditions that Peer highlights include Clostridium difficile infection, which has become strikingly more common in patients in the year after dialysis initiation, and chronic obstructive pulmonary disease, the treatments for which have the potential to contribute to sudden cardiac death. Finally, Peer challenges the nephrology community to consider alternatives to standardized mortality ratios in assessing progress in care, positing that close scrutiny of trends over time may be the most effective way to drive improvements in patient care. PMID- 27006496 TI - A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu-Expressing Tumor in HLA-A2 Transgenic Mice. AB - PURPOSE: E75, a peptide derived from the Her2/neu protein, is the most clinically advanced vaccine approach against breast cancer. In this study, we aimed to optimize the E75 vaccine using a delivery vector targeting dendritic cells, the B subunit of Shiga toxin (STxB), and to assess the role of various parameters (Her2/neu expression, combination with trastuzumab) in the efficacy of this cancer vaccine in a relevant preclinical model. EXPERIMENTAL DESIGN: We compared the differential ability of the free E75 peptide or the STxB-E75 vaccine to elicit CD8(+) T cells, and the impact of the vaccine on murine HLA-A2 tumors expressing low or high levels of Her2/neu. RESULTS: STxB-E75 synergized with granulocyte macrophage colony-stimulating factors and CpG and proved to be more efficient than the free E75 peptide in the induction of multifunctional and high avidity E75-specific anti-CD8(+) T cells resulting in a potent tumor protection in HLA-A2 transgenic mice. High expression of HER2/neu inhibited the expression of HLA-class I molecules, leading to a poor recognition of human or murine tumors by E75-specific cytotoxic CD8(+) T cells. In line with these results, STxB-E75 preferentially inhibited the growth of HLA-A2 tumors expressing low levels of Her2/neu. Coadministration of anti-Her2/neu mAb potentiated this effect. CONCLUSIONS: STxB-E75 vaccine is a potent candidate to be tested in patients with low Her2/neu-expressing tumors. It could also be indicated in patients expressing high levels of Her2/neu and low intratumoral T-cell infiltration to boost the recruitment of T cells-a key parameter in the efficacy of anti-Her2/neu mAb therapy. Clin Cancer Res; 22(16); 4133-44. (c)2016 AACR. PMID- 27006498 TI - A heme-binding domain controls regulation of ATP-dependent potassium channels. AB - Heme iron has many and varied roles in biology. Most commonly it binds as a prosthetic group to proteins, and it has been widely supposed and amply demonstrated that subtle variations in the protein structure around the heme, including the heme ligands, are used to control the reactivity of the metal ion. However, the role of heme in biology now appears to also include a regulatory responsibility in the cell; this includes regulation of ion channel function. In this work, we show that cardiac KATP channels are regulated by heme. We identify a cytoplasmic heme-binding CXXHX16H motif on the sulphonylurea receptor subunit of the channel, and mutagenesis together with quantitative and spectroscopic analyses of heme-binding and single channel experiments identified Cys628 and His648 as important for heme binding. We discuss the wider implications of these findings and we use the information to present hypotheses for mechanisms of heme dependent regulation across other ion channels. PMID- 27006499 TI - Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development. AB - Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-beta, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC. PMID- 27006500 TI - Quantitative MS-based enzymology of caspases reveals distinct protein substrate specificities, hierarchies, and cellular roles. AB - Proteases constitute the largest enzyme family, yet their biological roles are obscured by our rudimentary understanding of their cellular substrates. There are 12 human caspases that play crucial roles in inflammation and cell differentiation and drive the terminal stages of cell death. Recent N-terminomics technologies have begun to enumerate the diverse substrates individual caspases can cleave in complex cell lysates. It is clear that many caspases have shared substrates; however, few data exist about the catalytic efficiencies (kcat/KM) of these substrates, which is critical to understanding their true substrate preferences. In this study, we use quantitative MS to determine the catalytic efficiencies for hundreds of natural protease substrates in cellular lysate for two understudied members: caspase-2 and caspase-6. Most substrates are new, and the cleavage rates vary up to 500-fold. We compare the cleavage rates for common substrates with those found for caspase-3, caspase-7, and caspase-8, involved in apoptosis. There is little correlation in catalytic efficiencies among the five caspases, suggesting each has a unique set of preferred substrates, and thus more specialized roles than previously understood. We synthesized peptide substrates on the basis of protein cleavage sites and found similar catalytic efficiencies between the protein and peptide substrates. These data suggest the rates of proteolysis are dominated more by local primary sequence, and less by the tertiary protein fold. Our studies highlight that global quantitative rate analysis for posttranslational modification enzymes in complex milieus for native substrates is critical to better define their functions and relative sequence of events. PMID- 27006501 TI - Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT. AB - The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial-mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers. PMID- 27006502 TI - Differential volume regulation and calcium signaling in two ciliary body cell types is subserved by TRPV4 channels. AB - Fluid secretion by the ciliary body plays a critical and irreplaceable function in vertebrate vision by providing nutritive support to the cornea and lens, and by maintaining intraocular pressure. Here, we identify TRPV4 (transient receptor potential vanilloid isoform 4) channels as key osmosensors in nonpigmented epithelial (NPE) cells of the mouse ciliary body. Hypotonic swelling and the selective agonist GSK1016790A (EC50 ~33 nM) induced sustained transmembrane cation currents and cytosolic [Formula: see text] elevations in dissociated and intact NPE cells. Swelling had no effect on [Formula: see text] levels in pigment epithelial (PE) cells, whereas depolarization evoked [Formula: see text] elevations in both NPE and PE cells. Swelling-evoked [Formula: see text] signals were inhibited by the TRPV4 antagonist HC067047 (IC50 ~0.9 MUM) and were absent in Trpv4(-/-) NPE. In NPE, but not PE, swelling-induced [Formula: see text] signals required phospholipase A2 activation. TRPV4 localization to NPE was confirmed with immunolocalization and excitation mapping approaches, whereas in vivo MRI analysis confirmed TRPV4-mediated signals in the intact mouse ciliary body. Trpv2 and Trpv4 were the most abundant vanilloid transcripts in CB. Overall, our results support a model whereby TRPV4 differentially regulates cell volume, lipid, and calcium signals in NPE and PE cell types and therefore represents a potential target for antiglaucoma medications. PMID- 27006503 TI - Unique coupling of mono- and dioxygenase chemistries in a single active site promotes heme degradation. AB - Bacterial pathogens must acquire host iron for survival and colonization. Because free iron is restricted in the host, numerous pathogens have evolved to overcome this limitation by using a family of monooxygenases that mediate the oxidative cleavage of heme into biliverdin, carbon monoxide, and iron. However, the etiological agent of tuberculosis, Mycobacterium tuberculosis, accomplishes this task without generating carbon monoxide, which potentially induces its latent state. Here we show that this unusual heme degradation reaction proceeds through sequential mono- and dioxygenation events within the single active center of MhuD, a mechanism unparalleled in enzyme catalysis. A key intermediate of the MhuD reaction is found to be meso-hydroxyheme, which reacts with O2 at an unusual position to completely suppress its monooxygenation but to allow ring cleavage through dioxygenation. This mechanistic change, possibly due to heavy steric deformation of hydroxyheme, rationally explains the unique heme catabolites of MhuD. Coexistence of mechanistically distinct functions is a previously unidentified strategy to expand the physiological outcome of enzymes, and may be applied to engineer unique biocatalysts. PMID- 27006504 TI - Active sites and mechanisms for H2O2 decomposition over Pd catalysts. AB - A combination of periodic, self-consistent density functional theory (DFT-GGA PW91) calculations, reaction kinetics experiments on a SiO2-supported Pd catalyst, and mean-field microkinetic modeling are used to probe key aspects of H2O2 decomposition on Pd in the absence of cofeeding H2 We conclude that both Pd(111) and OH-partially covered Pd(100) surfaces represent the nature of the active site for H2O2 decomposition on the supported Pd catalyst reasonably well. Furthermore, all reaction flux in the closed catalytic cycle is predicted to flow through an O-O bond scission step in either H2O2 or OOH, followed by rapid H transfer steps to produce the H2O and O2 products. The barrier for O-O bond scission is sensitive to Pd surface structure and is concluded to be the central parameter governing H2O2 decomposition activity. PMID- 27006505 TI - Reply to Yu et al.: Global temperature change as the ultimate driver of the shift in the summer monsoon rain belt in East Asia. PMID- 27006506 TI - Anthropogenic aerosols are a potential cause for migration of the summer monsoon rain belt in China. PMID- 27006507 TI - Reply to Curry and Coombs: Benzoic acid is formed predominantly from the benzoyl ester hydrolysis in the presence of cocaine hydrolase. PMID- 27006508 TI - Benzoic acid is not the only important product of accelerated metabolism of cocaine. PMID- 27006509 TI - Commonly Measured Clinical Variables Are Not Associated With Burden of Complications in Long-standing Type 1 Diabetes: Results From the Canadian Study of Longevity in Diabetes. PMID- 27006510 TI - Association of Blood Glucose Control and Lipids With Diabetic Retinopathy in the Veterans Affairs Diabetes Trial (VADT). AB - OBJECTIVE: This study examined whether lipids modify the relationship between intensive glucose control (INT) and diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS: The incidence and progression of DR were assessed in 858 of 1,791 participants with 7-field stereoscopic fundus photographs at baseline and 5 years later. RESULTS: Odds of DR progression were lower by ~40% in those with baseline total cholesterol (TC) >=200 mg/dL (P = 0.007), LDL-C >=120 mg/dL (P < 0.02), or HDL-C >=40 mg/dL (P < 0.007) in the INT arm versus standard glycemic treatment. Odds of DR progression were reduced by ~40% in those who had TC <=140 mg/dL (P <= 0.024), triglycerides (TG) <=120 mg/dL (P = 0.004), or HDL-C >=45 mg/dL (P = 0.01) at the fifth year. Odds of DR progression were lower by ~40-50% with reductions of TC by >=40 mg/dL (P < 0.0001), of LDL-C of >=40 mg/dL (P < 0.004), and of TG by >=60 mg/dL (P = 0.004) at the fifth year. Odds of DR progression increased by 80% with increases in TC of >=20 mg/dL (P < 0.0001) and by 180% with increases in LDL-C by >=60 mg/dL (P < 0.004). After adjusting for covariants, those with higher TC at baseline and lower TC during and at the fifth year and higher HDL-C throughout study had significantly decreased odds of DR progression in INT. CONCLUSIONS: INT was associated with decreased odds of progression but not with onset of retinopathy in those with worse lipid levels at baseline and more improved lipid levels during the study. Higher HDL-C was consistently associated with better response to INT throughout the study. PMID- 27006511 TI - An Inverse Relationship Between Age of Type 2 Diabetes Onset and Complication Risk and Mortality: The Impact of Youth-Onset Type 2 Diabetes. AB - OBJECTIVE: This study compared the prevalence of complications in 354 patients with T2DM diagnosed between 15 and 30 years of age (T2DM15-30) with that in a duration-matched cohort of 1,062 patients diagnosed between 40 and 50 years (T2DM40-50). It also examined standardized mortality ratios (SMRs) according to diabetes age of onset in 15,238 patients covering a wider age-of-onset range. RESEARCH DESIGN AND METHODS: Complication status was assessed according to a standard protocol and extracted from our electronic database. Survival status was ascertained by data linkage with the Australian National Death Index. SMRs were calculated in comparison with the background Australian population and analyzed according to age of onset. RESULTS: After matching for duration, despite their younger age, T2DM15-30 had more severe albuminuria (P = 0.004) and neuropathy scores (P = 0.003). T2DM15-30 were as commonly affected by metabolic syndrome factors as T2DM40-50 but less frequently treated for hypertension and dyslipidemia (P < 0.0001). An inverse relationship between age of diabetes onset and SMR was seen, which was the highest for T2DM15-30 (3.4 [95% CI 2.7-4.2]). SMR plots adjusting for duration show that for those with T2DM15-30, SMR is the highest at any chronological age, with a peak SMR of more than 6 in early midlife. In contrast, mortality for older-onset groups approximates that of the background population. CONCLUSIONS: The negative effect of diabetes on morbidity and mortality is greatest for those diagnosed at a young age compared with T2DM of usual onset. These results highlight the growing imperative to direct attention toward young-onset T2DM and for effective interventions to be applied before middle age. PMID- 27006513 TI - Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study. AB - OBJECTIVE: Studies have suggested the association between autism spectrum disorder (ASD) and type 2 diabetes mellitus (DM)-related risk factors, such as obesity and dyslipidemia. However, the association between ASD and type 2 DM remains unknown. RESEARCH DESIGN AND METHODS: We used the Taiwan National Health Insurance Research Database for enrolling 6,122 adolescents and young adults with ASD and 24,488 age- and sex-matched control subjects between 2002 and 2009 and monitored them until the end of 2011. Participants who developed type 2 DM during the follow-up period were identified. RESULTS: Adolescents (hazard ratio [HR] 2.71 [95% CI 1.64-4.48]) and young adults (HR 5.31 [95% CI 2.85-9.90]) with ASD had a higher risk of developing type 2 DM than those without ASD, after adjustment for demographic data, atypical antipsychotics use, and medical comorbidities. Sensitivity analyses after excluding first year (HR 3.03 [95% CI 2.03-4.51]) and first 3-year (HR 2.62 [95% CI 1.62-4.23]) observation periods were consistent. Short-term (HR 1.97 [95% CI 1.20-3.23]) and long-term (HR 1.64 [95% CI 1.02-2.63]) use of atypical antipsychotics were associated with a higher likelihood of subsequent type 2 DM. CONCLUSIONS: Adolescents and young adults with ASD were more likely to develop type 2 DM during the follow-up. In addition, those with ASD using atypical antipsychotics exhibited a high risk. Therefore, further research is necessary to investigate the common pathophysiology of ASD and type 2 DM. PMID- 27006512 TI - Long-term Benefits of Intensive Glucose Control for Preventing End-Stage Kidney Disease: ADVANCE-ON. AB - OBJECTIVE: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial reported that intensive glucose control prevents end-stage kidney disease (ESKD) in patients with type 2 diabetes, but uncertainty about the balance between risks and benefits exists. Here, we examine the long-term effects of intensive glucose control on risk of ESKD and other outcomes. RESEARCH DESIGN AND METHODS: Survivors, previously randomized to intensive or standard glucose control, were invited to participate in post-trial follow-up. ESKD, defined as the need for dialysis or kidney transplantation, or death due to kidney disease, was documented overall and by baseline CKD stage, along with hypoglycemic episodes, major cardiovascular events, and death from other causes. RESULTS: A total of 8,494 ADVANCE participants were followed for a median of 5.4 additional years. In-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD (7 vs. 20 events, hazard ratio [HR] 0.35, P = 0.02) persisted after 9.9 years of overall follow-up (29 vs. 53 events, HR 0.54, P < 0.01). These effects were greater in earlier-stage CKD (P = 0.04) and at lower baseline systolic blood pressure levels (P = 0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function (P > 0.26). CONCLUSIONS: Intensive glucose control was associated with a long term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure. PMID- 27006514 TI - Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes. AB - OBJECTIVE: To ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. RESEARCH DESIGN AND METHODS: Fourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. RESULTS: Cognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non-sleep-deprived conditions. However, in the sleep-deprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P < 0.001) and hypoglycemia symptom scores were significantly higher (P < 0.001), even when symptoms that may have been caused by sleep deprivation, such as tiredness, were removed. CONCLUSIONS: Hypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period. PMID- 27006516 TI - Morphofunctional Merits of an In Vivo Cryotechnique for Living Animal Organs: Challenges of Clinical Applications from Basic Medical Research. AB - Recent advances in molecular and genetic techniques have led to establishment of new biomedical fields; however, morphological techniques are still required for a more precise understanding of functioning cells and tissues. Conventional preparation procedures involve a series of chemical fixation, alcohol dehydration, paraffin or epoxy resin embedding, sectioning, and staining steps. In these steps, technical artifacts modify original morphologies of the cells being examined. Furthermore, difficulties are associated with capturing dynamic images in vivo using conventional chemical fixation. Therefore, a quick-freezing (QF) method was introduced for biological specimens in the 20th century. However, specimens have to be resected from living animal organs with blood supply, and their dynamical morphologies have not been investigated in detail using the QF method. In order to overcome these issues, the tissue resection step of organs had to be avoided and samples needed to be frozen under blood circulation. Our in vivo cryotechnique (IVCT) was an original technique to cryofix samples without resecting their tissues. The most significant merit of IVCT is that blood circulation into organs is preserved at the exact moment of freezing, which has been useful for arresting transient physiological processes of cells and tissues and maintaining their components in situ. PMID- 27006517 TI - Enzyme-labeled Antigen Method: Development and Application of the Novel Approach for Identifying Plasma Cells Locally Producing Disease-specific Antibodies in Inflammatory Lesions. AB - In chronic inflammatory lesions of autoimmune and infectious diseases, plasma cells are frequently observed. Antigens recognized by antibodies produced by the plasma cells mostly remain unclear. A new technique identifying these corresponding antigens may give us a breakthrough for understanding the disease from a pathophysiological viewpoint, simply because the immunocytes are seen within the lesion. We have developed an enzyme-labeled antigen method for microscopic identification of the antigen recognized by specific antibodies locally produced in plasma cells in inflammatory lesions. Firstly, target biotinylated antigens were constructed by the wheat germ cell-free protein synthesis system or through chemical biotinylation. Next, proteins reactive to antibodies in tissue extracts were screened and antibody titers were evaluated by the AlphaScreen method. Finally, with the enzyme-labeled antigen method using the biotinylated antigens as probes, plasma cells producing specific antibodies were microscopically localized in fixed frozen sections. Our novel approach visualized tissue plasma cells that produced 1) autoantibodies in rheumatoid arthritis, 2) antibodies against major antigens of Porphyromonas gingivalis in periodontitis or radicular cyst, and 3) antibodies against a carbohydrate antigen, Strep A, of Streptococcus pyogenes in recurrent tonsillitis. Evaluation of local specific antibody responses expectedly contributes to clarifying previously unknown processes in inflammatory disorders. PMID- 27006518 TI - Expression of Vesicular Nucleotide Transporter in Rat Odontoblasts. AB - Several theories have been proposed regarding pain transmission mechanisms in tooth. However, the exact signaling mechanism from odontoblasts to pulp nerves remains to be clarified. Recently, ATP-associated pain transmission has been reported, but it is unclear whether ATP is involved in tooth pain transmission. In the present study, we focused on the vesicular nucleotide transporter (VNUT), a transporter of ATP into vesicles, and examined whether VNUT was involved in ATP release from odontoblasts. We examined the expression of VNUT in rat pulp by RT PCR and immunostaining. ATP release from cultured odontoblast-like cells with heat stimulation was evaluated using ATP luciferase methods. VNUT was expressed in pulp tissue, and the distribution of VNUT-immunopositive vesicles was confirmed in odontoblasts. In odontoblasts, some VNUT-immunopositive vesicles were colocalized with membrane fusion proteins. Additionally P2X3, an ATP receptor, immunopositive axons were distributed between odontoblasts. The ATP release by thermal stimulation from odontoblast-like cells was inhibited by the addition of siRNA for VNUT. These findings suggest that cytosolic ATP is transported by VNUT and that the ATP in the vesicles is then released from odontoblasts to ATP receptors on axons. ATP vesicle transport in odontoblasts seems to be a key mechanism for signal transduction from odontoblasts to axons in the pulp. PMID- 27006519 TI - Histopathological Characteristics of Post-inflamed Coronary Arteries in Kawasaki Disease-like Vasculitis of Rabbits. AB - Kawasaki disease (KD) is a systemic vasculitis in infants that develops predominantly in the coronary arteries. Despite the clinically transient nature of active inflammation in childhood albeit rare complications (e.g., coronary artery aneurysm), KD has recently been suggested to increase the incidence of ischemic heart diseases in young adulthood. However, little is known about the histopathology of the coronary artery long after development of the acute KD vasculitis. To address this, we conducted histological studies of rabbit coronary arteries in adolescent phase after induction of the KD-like vasculitis induced by horse serum administration. After a transmural infiltration of inflammatory cells in acute phase at day 7, the artery exhibited a gradual decrease in the number of inflammatory cells and thickening of the intima during the chronic phase up to day 90, where proteoglycans were distinctly accumulated in the intima with abundant involvement of alpha-smooth muscle actin (alpha-SMA)-positive cells, most of which accompanied expression of VCAM-1 and NF-kappaB. Distinct from classical atherosclerosis, inflammatory cells, e.g., macrophages, were barely detected during the chronic phase. These observations indicate that the KD-like coronary arteritis is followed by intimal thickening via accumulation of proteoglycans and proliferation of alpha-SMA-positive cells, reflecting aberrant coronary artery remodeling. PMID- 27006520 TI - Expression of Sex Steroid Hormone Receptors in Vagal Motor Neurons Innervating the Trachea and Esophagus in Mouse. AB - The medullary vagal motor nuclei, the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV), innervate the respiratory and gastrointestinal tracts. We conducted immunohistochemical analysis of expression of the androgen receptor (AR) and estrogen receptor alpha (ERalpha), in relation to innervation of the trachea and esophagus via vagal motor nuclei in mice. AR and ERalpha were expressed in the rostral NA and in part of the DMV. Tracing experiments using cholera toxin B subunit demonstrated that neurons of vagal motor nuclei that innervate the trachea and esophagus express AR and ERalpha. There was no difference in expression of sex steroid hormone receptors between trachea- and esophagus-innervating neurons. These results suggest that sex steroid hormones may act on vagal motor nuclei via their receptors, thereby regulating functions of the trachea and esophagus. PMID- 27006522 TI - Assessment of remineralized dentin lesions with thermal and near-infrared reflectance imaging. AB - Accurate detection and measurement of the highly mineralized surface layer that forms on caries lesions is important for the diagnosis of lesion activity. Previous studies have demonstrated that optical imaging methods can be used to measure the degree of remineralization on enamel lesions. The purpose of this study was to determine if thermal and near-IR reflectance imaging could be used to assess the remineralization process in simulated dentin lesions. Artificial bovine (n=15) dentin lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for up to 12 days. The samples were dehydrated using an air spray for 30 seconds and imaged using thermal and InGaAs cameras. The area enclosed by the time-temperature curve, DeltaQ, from thermal imaging decreased significantly with longer periods of remineralization. However, near-IR reflectance intensity differences, DeltaI, before and after dehydration failed to show any significant relationship with the degree of remineralization. This study shows that thermal imaging can be used for the assessment of the remineralization of dentin lesions. PMID- 27006521 TI - A new sealed RF-excited CO2 laser for enamel ablation operating at 9.4-MUm with a pulse duration of 26-MUs. AB - Several studies over the past 20 years have shown that carbon dioxide lasers operating at wavelengths between 9.3 and 9.6-MUm with pulse durations near 20-MUs are ideal for hard tissue ablation. Those wavelengths are coincident with the peak absorption of the mineral phase. The pulse duration is close to the thermal relaxation time of the deposited energy of a few microseconds which is short enough to minimize peripheral thermal damage and long enough to minimize plasma shielding effects to allow efficient ablation at practical rates. The desired pulse duration near 20-MUs has been difficult to achieve since it is too long for transverse excited atmospheric pressure (TEA) lasers and too short for radio frequency (RF) excited lasers for efficient operation. Recently, Coherent Inc. (Santa Clara, CA) developed the Diamond J5-V laser for microvia drilling which can produce laser pulses greater than 100-mJ in energy at 9.4-MUm with a pulse duration of 26-MUs and it can achieve pulse repetition rates of 3 KHz. We report the first results using this laser to ablate dental enamel. Efficient ablation of dental enamel is possible at rates exceeding 50-MUm per pulse. This laser is ideally suited for the selective ablation of carious lesions. PMID- 27006523 TI - Evaluation of enamel surface modification using PS-OCT after laser treatment to increase resistance to demineralization. AB - At laser intensities below ablation, carbonated hydroxyapatite in enamel is converted into a purer phase hydroxyapatite with increased acid resistance. Previous studies suggested the possibility of achieving the conversion without surface modification. This study attempts to evaluate the thresholds for the modification without additional changes in physical and optical properties of the enamel. Bovine specimens were irradiated using an RF-excited CO2 laser operating at 9.4-um with a pulse duration of 26-us, pulse repetition rates of 100-1000 Hz, with a Gaussian spatial beam profile - 1.4 mm in diameter. After laser treatment, the samples were subjected to acid demineralization for 48 hours to simulate acidic intraoral conditions of a caries attack. The resulting demineralization and erosion were assessed using polarization sensitive OCT (PS-OCT) and 3D digital microscopy. The images from digital microscopy demonstrated a clear delineation between laser protected zones without visual changes and zones with higher levels of demineralization and erosion. Distinct changes in the surface morphology were found within the laser treated area in accordance with the Gaussian spatial beam profile. There was significant protection from the laser in areas that were not visually altered. PMID- 27006524 TI - A system for simultaneous near-infrared reflectance and transillumination imaging of occlusal carious lesions. AB - Clinicians need technologies to improve the diagnosis of questionable occlusal carious lesions (QOC's) and determine if decay has penetrated to the underlying dentin. Assessing lesion depth from near-infrared (NIR) images holds great potential due to the high transparency of enamel and stain to NIR light at lambda=1300-1700-nm, which allows direct visualization and quantified measurements of enamel demineralization. Unfortunately, NIR reflectance measurements alone are limited in utility for approximating occlusal lesion depth >200-MUm due to light attenuation from the lesion body. Previous studies sought to combine NIR reflectance and transillumination measurements taken at lambda=1300-nm in order to estimate QOC depth and severity. The objective of this study was to quantify the change in lesion contrast and size measured from multispectral NIR reflectance and transillumination images of natural occlusal carious lesions with increasing lesion depth and severity in order to determine the optimal multimodal wavelength combinations for estimating QOC depth. Extracted teeth with varying amounts of natural occlusal decay were measured using a multispectral-multimodal NIR imaging system at prominent wavelengths within the lambda=1300-1700-nm spectral region. Image analysis software was used to calculate lesion contrast and area values between sound and carious enamel regions. PMID- 27006526 TI - HIV Progression Perturbs the Balance of the Cell-Mediated and Anti-Inflammatory Adaptive and Innate Mycobacterial Immune Response. AB - INTRODUCTION: Our objective is to understand how HIV infection increases the risk of progression from latent tuberculosis (TB) to active disease. We understand now that immunity is a balance of competing immune responses by multiple cell types. Since T-lymphocyte production of interferon-gamma (IFN-gamma) in response to Mycobacterium tuberculosis (Mtb) antigens fails to differentiate disease from latent infection, we applied a comprehensive profiling methodology to define immune biomarkers that reliably predict a patient's TB risk. METHODS: We established a cohort of HIV-infected adults with TB disease from Swaziland. Multiparametric flow cytometry was used to quantify the mycobacterial-specific anti-inflammatory (IL-4 and IL-10) and proinflammatory (IFN-gamma) immune response. RESULTS: From 12 HIV-infected Swaziland patients with TB disease, the CD4(+), CD8(+), Double Negative, and CD56(+)CD3(-) lymphocytes increase their IL 4 : IFN-gamma ratio as HIV disease worsens (Spearman r of -0.59; -0.59; -0.60; and -0.59, resp.; p < 0.05). Similarly, HIV severity is associated with an increased IL-10 : IFN-gamma ratio (Spearman r of -0.76; p = 0.01). CONCLUSION: As HIV disease progresses, both the adaptive and innate branches skew away from an inflammatory and towards anti-inflammatory phenotype. PMID- 27006527 TI - Basic and Clinical Advances in Chronic Liver Inflammation. PMID- 27006525 TI - Why Current Doppler Ultrasound Methodology Is Inaccurate in Assessing Cerebral Venous Return: The Alternative of the Ultrasonic Jugular Venous Pulse. AB - Assessment of cerebral venous return is growing interest for potential application in clinical practice. Doppler ultrasound (DUS) was used as a screening tool. However, three meta-analyses of qualitative DUS protocol demonstrate a big heterogeneity among studies. In an attempt to improve accuracy, several authors alternatively measured the flow rate, based on the product of the time average velocity with the cross-sectional area (CSA). However, also the quantification protocols lacked of the necessary accuracy. The reasons are as follows: (a) automatic measurement of the CSA assimilates the jugular to a circle, while it is elliptical; (b) the use of just a single CSA value in a pulsatile vessel is inaccurate; (c) time average velocity assessment can be applied only in laminar flow. Finally, the tutorial describes alternative ultrasound calculation of flow based on the Womersley method, which takes into account the variation of the jugular CSA overtime. In the near future, it will be possible to synchronize the electrocardiogram with the brain inflow (carotid distension wave) and with the outflow (jugular venous pulse) in order to nicely have a noninvasive ultrasound picture of the brain-heart axis. US jugular venous pulse may have potential use in neurovascular, neurocognitive, neurosensorial, and neurodegenerative disorders. PMID- 27006528 TI - Ion Channels in Inflammatory Processes: What Is Known and What Is Next? PMID- 27006529 TI - Sphingolipids in Inflammation: From Bench to Bedside. PMID- 27006530 TI - IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin. AB - Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents. PMID- 27006532 TI - The revised guidelines of the Medical Council of India for academic promotions: Need for a rethink. PMID- 27006531 TI - Apoptosis through Death Receptors in Temporal Lobe Epilepsy-Associated Hippocampal Sclerosis. AB - Seizure models have demonstrated that neuroinflammation and neurodegeneration are preponderant characteristics of epilepsy. Considering the lack of clinical studies, our aim is to investigate the extrinsic pathway of apoptosis in pharmacoresistant temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) patients, TLE(HS). By a specific death receptor-mediated apoptosis array plate, 31 upregulated targets were revealed in the sclerotic hippocampus from TLE(HS) patients. Amongst them are the encoding genes for ligands (FASLG, TNF, and TNFSF10) and death receptors (FAS, TNFRSF1A, TNFRSF10A, and TNFRSF10B). In addition, we evaluated the hippocampal relative mRNA expression of the two TNF receptors, TNFRSF1A and TNFRSF1B, in patients, being both upregulated (n = 14; P < 0.01 and P < 0.04, resp.) when compared to the post mortem control group (n = 4). Our results have clearly suggested that three different death receptor apoptotic systems may be associated with the maintenance and progression of TLE associated HS: (1) TNF-TNFRSF1A, (2) FASLG-FAS, and (3) TNFSF10-TNFRSF10A/B. Their effects on epilepsy are still scarcely comprehended. Our study points out to TNF and TNF receptor superfamily pathways as important targets for pharmacological studies regarding the benefits of an anti-inflammatory therapy in these patients. PMID- 27006533 TI - Postoperative analgesia for cleft lip and palate repair in children. AB - Acute pain such as postoperative pain during infancy was ignored approximately three decades ago due to biases and misconceptions regarding the maturity of the infant's developing nervous system, their inability to verbally report pain, and their perceived inability to remember pain. More recently, these misconceptions are rarely acknowledged due to enhanced understanding of the developmental neurobiology of infant pain pathways and supraspinal processing. Cleft lip and palate is one of the most common congenital abnormalities requiring surgical treatment in children and is associated with intense postoperative pain. The pain management gets further complicated due to association with postsurgical difficult airway and other congenital anomalies. Orofacial blocks like infraorbital, external nasal, greater/lesser palatine, and nasopalatine nerve blocks have been successively used either alone or in combinations to reduce the postoperative pain. Since in pediatric population, regional anesthesia is essentially performed under general anesthesia, association of these two techniques has dramatically cut down the risks of both procedures particularly those associated with the use of opioids and nonsteroidal anti-inflammatory drugs. Definitive guidelines for postoperative pain management in these patients have not yet been developed. Incorporation of multimodal approach as an institutional protocol can help minimize the confusion around this topic. PMID- 27006534 TI - Comparison of hemodynamic response to adrenaline infiltration in children undergoing cleft palate repair during general anesthesia with sevoflurane and isoflurane. AB - BACKGROUND AND AIMS: Systemic absorption of adrenaline often used for infiltration during cleft palate surgery leads to adverse hemodynamic responses. These hemodynamic responses may be attenuated by the volatile anesthetics. This study aims to compare the hemodynamic responses to adrenaline infiltration during isoflurane (ISO) and sevoflurane (SEVO) anesthesia. MATERIAL AND METHODS: Sixty children aged between 9 months and 48 months, weighing between 8 kg and 20 kg, undergoing primary repair of cleft palate were randomly allocated into two groups: Group ISO - anesthesia maintained with ISO (2 minimum alveolar concentrations [MAC]) and nitrous oxide 50% and group SEVO - maintained on SEVO (2 MAC) and nitrous oxide 50%. Surgical site was infiltrated with 1 ml/kg of 1:200,000 solution of adrenaline with 0.5% lignocaine. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were noted at the end of infiltration and every 1 min for 5 min following infiltration. The percentage change of hemodynamic responses from baseline, following infiltration were compared between the two groups. RESULTS: There was no significant change in HR from baseline, and the response was comparable between the agents at all times. The blood pressure (BP) increased from baseline in both the groups but the increase was greater in SEVO than ISO group at 2 and 3 min after infiltration. The maximum change in HR from baseline (group ISO median 10.9% [interquartile range (IQR) 4.5-23.0] vs. group SEVO 26.5% [11.9-44.6]) was comparable in both the groups (P = 0.169). The maximum change in SBP was significantly greater in group SEVO than group ISO (42.8% [IQR 20.0-60.9] vs. 26.0 [11.3-44.5], P = 0.04). The incidence of significant change (>20%) of SBP, DBP, and MAP from baseline was significantly greater in group SEVO after infiltration and 1 min and 2 min after infiltration. There were no arrhythmias in any of the groups. CONCLUSION: Isoflurane results in greater attenuation of rise in BP during adrenaline infiltration compared to SEVO at similar MAC. PMID- 27006535 TI - Efficacy of a separate informed consent for anesthesia services: A prospective study from the Caribbean. AB - BACKGROUND AND AIMS: This study aimed to determine whether a separate written consent form improved the efficacy of the informed consent process for anesthesia in adult patients undergoing elective surgery at a tertiary care teaching hospital. MATERIAL AND METHODS: We randomized patients into two groups prospectively. The first group (Group A) signed the hospital's standard Consent for Operation form only while the second group (Group B) signed a separate Consent for Anesthesia form additionally. Patients were interviewed postoperatively with an eight-item questionnaire with responses in a 5-point Likert scale. A composite adequacy of consent index was generated from the responses and analyzed. RESULTS: Two hundred patients (100 in each group) were studied. All patients indicated that the anesthesiologist(s) had their permission to proceed with their anesthesia care. The mean adequacy of consent index score in Group B was higher than that of Group A (30.6 +/- 4.6 [standard deviation (SD)] vs. 27.9 +/- 5.2 [SD]) (P < 0.001). The separate written consent had a positive impact on the patients' understanding of the nature and purpose of the intended anesthesia procedures (P = 0.04), satisfaction with the adequacy of information provided about common side effects (P < 0.001) and rare but serious complications (P = 0.008). CONCLUSIONS: A separate written consent for anesthesia improved the efficacy of the informed consent process with respect to better information about the nature and purpose of anesthesia, common side effects, and rare but serious complications. PMID- 27006536 TI - Sonographic assessment of predictors of depth of the corner pocket for ultrasound guided supraclavicular brachial plexus block. AB - BACKGROUND AND AIMS: There is wide variation in depth of brachial plexus in patient population at supraclavicular region. We plan to find the depth of the corner pocket and correlate it with age, weight, height and body mass index (BMI). MATERIAL AND METHODS: After approval from Ethics Committee, right-sided supraclavicular region of volunteers was scanned. Once an optimal image, which included subclavian artery, pleura, first rib and nerve bundles, was obtained, the corner pocket was kept in the middle of the screen and the image was frozen. Depth of the corner pocket from the skin was measured. Thereafter longest distance (LD) approximating needle trajectory was calculated. The Pearson correlation was used to calculate the relation between these two distances and various predictors such as weight, height, and BMI. RESULTS: Mean shortest distance that is, vertical distance from skin to corner pocket for all volunteers was found to be 1.7 +/- 0.8 cm and the mean LD that is, distance traveled by needle entering 1 cm from the edge of foot process to the corner pocket in an in plane approach was 3.7 +/- 0.2 cm. We did not find any significant correlation between age, height versus measured distances. However, significant correlation (0.11) was found between weights, BMI versus two lengths. CONCLUSION: Prescanning of supraclavicular region for estimating depth of corner pocket should be done before choosing an appropriate size needle. Furthermore, the needle should not be advanced more than the predicted corner pocket depth. PMID- 27006537 TI - Comparative study evaluating efficacy of sufentanil versus midazolam in preventing myoclonic movements following etomidate. AB - BACKGROUND AND AIMS: Myoclonus is a major side-effect following etomidate injection requiring use of medical intervention. MATERIAL AND METHODS: In this double-blinded clinical trial, 50 consecutive patients, randomly received sufentanil 0.2 MUg/kg or midazolam 0.015 mg/kg, 90 s before induction of anesthesia with etomidate (0.3 mg/kg). Then, the patients were monitored for any myoclonic movements during anesthesia. RESULTS: The incidence of myoclonus was 28% in the sufentanil group and 84% in the midazolam group. The frequency and intensity of myoclonus were significantly higher in the midazolam group, compared to the sufentanil group (P < 0.001). Myoclonus duration in the sufentanil and midazolam groups were 5.8 +/- 13.2 and 69 +/- 47.8 s, respectively (P < 0.0010). CONCLUSION: The frequency, intensity and duration of myoclonus in the midazolam group, were significantly more prevalent than the sufentanil group. PMID- 27006538 TI - A comparative study of early and late extubation following transoral odontoidectomy and posterior fixation. AB - BACKGROUND AND AIMS: Elective ventilation is the usual practice after transoral odontoidectomy (TOO) and posterior fixation. This practice of elective ventilation is not based on any evidence. The primary objective of our study was to find out the difference in oxygenation and ventilation in patients extubated early compared to those extubated late after TOO and posterior fixation. The secondary objectives were to compare the length of Intensive Care Unit (ICU)/hospital stay and pulmonary complications between the two groups. MATERIAL AND METHODS: After TOO and posterior fixation, patients were either extubated in the operating room (Group E) or extubated next day (Group D). The oxygenation (PaO2:FiO2 ratio) and ventilation (PaCO2) of the two groups before surgery, at 30 min and at 6/12/24 and 48 h after extubation were compared. Complications, durations of ICU and hospital stay were noted. RESULTS: The base-line PaO2:FiO2 and PaCO2 was comparable between the groups. No significant change in the PaO2:FiO2 was noted in the postoperative period in either group as compared to the preoperative values. Except for at 12 h after surgery, there was no significant difference between the two groups at various time intervals. No significant change in the PaCO2 level was seen during the study period in either group. PaCO2 measured at 30 min after surgery was more in Group E (37.5 +/- 3.2 mmHg in Group E vs. 34.6 +/- 2.9 mmHg in Group D), otherwise there was no significant difference between the two groups at various time intervals. One patient in Group E (7.1%) and two patients in Group D (13%) developed postoperative respiratory complication, but the difference was not statistically significant. The mean ICU stay (Group D = 42 +/- 25 h vs. Group E = 25.1 +/- 16.9 h) and mean hospital stay (Group D = 9.9 +/- 4 days vs. Group E = 7.6 +/- 2.2 days) were longer in Group D patients. CONCLUSION: Ventilation and oxygenation in the postoperative period in patients undergoing TOO and posterior fixation are not different between the two groups. However, the duration of ICU and hospital stay was prolonged in group D. PMID- 27006539 TI - Double blind comparison of combination of 0.1% ropivacaine and fentanyl to combination of 0.1% bupivacaine and fentanyl for extradural analgesia in labour. AB - BACKGROUND AND AIMS: Ropivacaine is considered as a safe alternative to bupivacaine for labor analgesia. The aim was to compare epidural ropivacaine and bupivacaine in intermittent doses for obstetric analgesia. MATERIAL AND METHODS: In this prospective, randomized, double-blind study, 60 women in labor were randomly allocated to receive either bupivacaine 0.1% with fentanyl 2 MUg/mL (BF), or ropivacaine 0.1% with fentanyl 2 MUg/mL (RF). Bromage scale, loss of cold sensation to ether swab in midclavicular line, visual analog scale were used to test for motor block, sensory block and pain, respectively. Hemodynamic parameters, onset of analgesia, dose requirement of drug to produce analgesia, duration of labor, and incidence of side effects were also recorded. Data were expressed as mean +/- standard deviation and analyzed using students unpaired t test, Chi-square and Mann-Whitney U-tests at P < 0.05. RESULTS: Both drugs were similar with respect to hemodynamic stability, onset of analgesia, quality of analgesia, sensory blockade, neonatal outcome, requirement of drugs, duration of labor, and incidence of side effects. Three parturient in bupivacaine (B-F) group had a motor block of Bromage 1 and were delivered using forceps. None of the parturient in ropivacaine (R-F) group had any motor block, and all had spontaneous vaginal delivery, but this difference was not statistically significant (P = 0.081). CONCLUSIONS: Bupivacaine and ropivacaine provide equivalent analgesia in low (0.1%) concentration. PMID- 27006540 TI - Addition of low-dose ketamine to midazolam and low-dose bupivacaine improves hemodynamics and postoperative analgesia during spinal anesthesia for cesarean section. AB - BACKGROUND AND AIMS: Spinal anesthesia for cesarean section (CS) is associated with an incidence of hypotension of 60-94%. This study hypothesizes that intrathecal combination of low-dose ketamine, midazolam, and low-dose bupivacaine improves hemodynamics and postoperative analgesia compared with fentanyl and low dose bupivacaine during CS. MATERIAL AND METHODS: Fifty parturients undergoing elective CS were randomized equally to receive ketamine (10 mg), midazolam (2 mg) and 0.5% hyperbaric bupivacaine (8 mg) in group ketamine-midazolam-bupivacaine (KMB) or fentanyl (25 MUg) and 0.5% hyperbaric bupivacaine (8 mg) in group fentanyl-bupivacaine (FB). Heart rate (HR), mean arterial blood pressure (MAP), oxygen saturation, sensorimotor block characteristics, pain-free period, side effects including: hypotension, bradycardia, nausea, vomiting, sedation, pruritus, respiratory depression and dissociative manifestations, Apgar score at 1 and 5 min, and patients' satisfaction visual analog scores (VAS) were recorded. Patients in group KMB were followed for 6 months in order to assess any neurological disorder. RESULTS: Group KMB showed higher sensory level (P = 0.006), rapid sensory (P = 0.001) and motor (P = 0.005) onsets, prolonged sensory (P = 0.008) and motor (P = 0.002) blocks, and prolonged pain free period (P = 0.002). Ketamine-midazolam stabilized HR and MAP, and significantly reduced incidence of hypotension (P = 0.002), bradycardia (P = 0.013) and vomiting (P = 0.019). Apgar scores at 1 and 5 min were comparable in both groups (P = 0.699 and 0.646 respectively). Patients' satisfaction VAS scores were significantly higher in group KMB (P = 0.001). No patients in KMB group showed dissociative or neurotoxic manifestations. CONCLUSION: Intrathecal low-dose ketamine combined with midazolam and low-dose bupivacaine stabilizes hemodynamics and prolongs postoperative analgesia without significant side-effects in parturients undergoing CS. PMID- 27006541 TI - Airway management and postoperative length of hospital stay in patients undergoing head and neck cancer surgery. AB - BACKGROUND AND AIMS: General anesthesia and airway management of patients for head and neck cancer surgery is a challenge for the anesthesiologist. Appropriate assessment and planning are essential for successful airway management. Our objectives were to review airway management strategies in patients undergoing head and neck cancer surgery in our tertiary care institution and also to observe the effect of airway management techniques on postoperative length of hospital stay (PLOS). MATERIAL AND METHODS: A retrospective medical record review of 400 patients who underwent major head and neck cancer surgery in our institution was conducted. A special form was used, and records were searched for airway and anesthetic management in the operating room and recovery room, and for PLOS. RESULTS: 289 (72.25%) of the patients were male, and 111 (27.75%) female. 49.8% of patients had Mallampati score of 3 and 4. Airway was managed with tracheostomy in 81 (20.25%) patients; nasal intubation was performed in 177 (44.25%) and oral intubation in 142 (35.5%) patients. Postoperative emergency tracheostomy was not done in any of the patients. CONCLUSION: Median postoperative hospital stay was significantly longer (P = 0.0005) in patients who had a tracheostomy performed compared with those where the airway was managed without it. PMID- 27006542 TI - Dexmedetomidine provides optimum conditions during awake fiberoptic intubation in simulated cervical spine injury patients. AB - BACKGROUND AND AIMS: We undertook this study to assess if a small-dose of dexmedetomidine (DEX) for conscious sedation during awake fiberoptic intubation (AFOI) in simulated cervical spine injury (CSI) patients provides optimum conditions and fulfills the need of postintubation neurological examination required in such patients. The aim was to assess the efficacy of DEX on arousability and patient's comfort during AFOI in simulated CSI patients. MATERIAL AND METHODS: In this prospective, randomized double-blind study, 100 American Society of Anesthesiologists Grade I-II patients aged between 18 and 65 years scheduled for elective surgery under general anesthesia underwent AFOI under conscious sedation with DEX. After locally anesthetizing the airway and applying a cervical collar, patients either received DEX 1 MUg/kg over 10 min followed by 0.7 MUg/kg/h maintenance infusion or normal saline in the same dose and rate during AFOI. Targeted sedation (Ramsay sedation score [RSS] >=2) during AFOI was maintained with midazolam [MDZ] in both groups. Statistical Analysis was performed using unpaired Student's t-test, Chi-square test, Mann-Whitney test and Wilcoxon-w test. RESULTS: The total number of patients requiring MDZ and the mean dose of MDZ required to achieve targeted sedation (RSS >=2) was significantly less in DEX group compared to the placebo group (P < 0.001). Similarly, patient satisfaction score, heart rate, systolic, diastolic and mean arterial pressure and respiratory parameters were significantly better in DEX group (P < 0.001). Postintubation arousability in the two groups was comparable (P = 0.29). CONCLUSIONS: Dexmedetomidine provides optimum sedation without compromising airway or hemodynamic instability with better patient tolerance and satisfaction for AFOI. It also preserves patient arousability for the postintubation neurological assessment. PMID- 27006543 TI - Comparative effectiveness of McCoy laryngoscope and CMAC((r)) videolaryngoscope in simulated cervical spine injuries. AB - BACKGROUND: Videolaryngoscopes are increasingly being used in potentially difficult airway. McCoy laryngoscope provides definitive advantage over conventional laryngoscopes in cervical spine patients. The aim of this study was to compare the performance of the CMAC((r)) videolaryngoscope with the McCoy Laryngoscope in patients with a cervical collar. MATERIAL AND METHODS: Sample size of at least 22 patients in each group was calculated using Intubation Difficulty Scale (IDS) score as the primary outcome. 60 American Society of Anesthesiologists I and II patients requiring tracheal intubation for elective surgery were randomly allocated into the McCoy group (n = 30) and the CMAC((r)) videolaryngoscope group (n = 30). Anesthesia was induced with fentanyl 2 mcg/kg, propofol 2-3 mg/kg and rocuronium 0.6 mg/kg. A rigid collar was applied to immobilize the cervical spine. Comparative data on the IDS scale, Cormack-Lehane (CL) laryngoscopic view, time taken for glottis visualization, time taken to pass endotracheal tube, total time to intubate, number of optimizing maneuvers and hemodynamic variables were recorded in the two groups. RESULTS: IDS score was significantly less in the CMAC((r)) group compared to the McCoy group (median [interquartile range (IQR)], 1 [0-1] vs. 4 [3-6], P < 0.05). CMAC((r)) videolaryngoscope required significantly less time for glottic visualization with median (IQR), 5 (5-7) versus 14 (8-15), P = 0.000 in McCoy laryngoscope, 29 (96.7%) patients in the CMAC((r)) group had Modified CL Grade I compared with 16 (53.3%) patients in McCoy group. The hemodynamic variables, number of optimizing maneuvers and incidence of side effects were comparable in the two groups. CONCLUSION: CMAC((r)) videolaryngoscope forms an effective tool for the airway management of cervical spine patients with a cervical collar. PMID- 27006544 TI - Epidural catheter fixation. A comparison of subcutaneous tunneling versus device fixation technique. AB - BACKGROUND AND AIMS: The technique of securing the epidural catheter has a major bearing on the efficacy of epidural analgesia. Specific fixator devices, for e.g., Lockit epidural catheter clamp, which successfully prevents catheter migration, are available. The possibility of catheter snapping and surgical retrieval has been reported with tunneling of catheters. These techniques have not been compared for safety, efficacy and appropriateness of achieving secure epidural catheter fixation in the postoperative period. MATERIAL AND METHODS: A total of 200 patients who required postoperative epidural analgesia were included. They were randomized into two groups: Group I (n = 100) in whom epidural catheters were tunneled vertically in the paravertebral subcutaneous tissue and group II (n = 100) wherein a Lockit device was used to fix the catheter. Likert score was used to quantify patient's comfort during procedure. The techniques were compared for migration, catheter dislodgement, local trauma, catheter snapping and catheter obstruction. RESULTS: 12% of tunneled catheters had migrated significantly outward. 22% of patients had erythema and 77% had significant procedural discomfort in group I. In group II, 3% catheters had kinked and 14% had erythema from device adhesive. CONCLUSION: Our results support the use of Lockit device as a safe and comfortable fixation device compared to subcutaneous tunneling of catheters. PMID- 27006545 TI - Attenuation of pressor response following intubation: Efficacy of nitro-glycerine lingual spray. AB - BACKGROUND AND AIMS: The role of nitro-glycerine (NTG) lingual spray for attenuation of the hemodynamic response associated with intubation is not much investigated. We conducted this study to evaluate the efficacy of NTG lingual pump or pen spray in attenuation of intubation induced hemodynamic responses and to elucidate the optimum dose. MATERIAL AND METHODS: In a prospective randomized controlled trial, 90 adult patients of ASA I, II, 18-60 year posted for elective general surgery under general anesthesia with intubation were randomly allocated to three groups as Group C (control) - receiving no NTG spray, Group N1 - receiving 1 NTG spray and Group N2 - receiving 2 NTG spray one minute before intubation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate were recorded at baseline, just before intubation (i.e., 60 s just after induction and NTG spray), immediately after intubation, at 1, 2, 5 and 10 min after intubation. RESULTS: Incidence of hypertension was significantly higher in Group C (60%, n = 18) as compared to Group N1 and N2 (10%, n = 3 each), P < 0.01. Mean value of SBP, DBP and MAP showed a significant rise as compared to baseline, following intubation in control group (15.31% in SBP, 12.12% in DBP, 17.77% in MAP) that persisted till 5 min, while no significant rise was observed in Group N1 and N2. There was a trend toward fall in blood pressure in Group N2 (4.95% fall in SBP, 4.72% fall in MAP) 1-min following spray, which was clinically insignificant. Mean value of SBP, DBP and MAP was significantly higher in Group C than in Group N1, which was in turn greater than Group N2 (Group C > N1> N2), P < 0.05. However, incidence of tachycardia was comparable in three groups (70% in group C, 63.33% in Group N1 and 67.77% in Group N2, P > 0.05). CONCLUSIONS: We concluded that the NTG lingual spray in dose of 0.4 mg (1 spray) or 0.8 mg (2 sprays) was effective in attenuation of intubation induced hemodynamic response, in terms of preventing significant rise in SBP, DBP and MAP compared to control group. PMID- 27006546 TI - Validation of simple and inexpensive algometry using sphygmomanometer cuff and neuromuscular junction monitor with standardized laboratory algometer. AB - BACKGROUND AND AIMS: The availability, ergonomics and economics prohibit the routine use of algometers in clinical practice and research by the anesthesiologists. A simple bedside technique of quantitative pain measurement would enable the routine use of algometry. We proposed to validate simple pain provocation using sphygmomanometer cuff and the electric stimulation of neuromuscular junction monitor (TOF-guard, Organon Teknika) to measure pain against a standardized laboratory pressure algometer. MATERIAL AND METHODS: Pain detection threshold (Pdt) and pain tolerance threshold (Ptt) were measured in forty healthy volunteers of both genders, using the above three techniques. All measurements were repeated three times. The co-efficient of inter-rater reliability (or consistency) between three independent measurements obtained from each of the techniques was determined by Cronbach's co-efficient alpha (alpha C). The correlation between the mean Pdt and Ptt values recorded by standardized algometer and the sphygmomanometer technique and nerve stimulator technique was performed using Pearson Correlation. An r >0.5 and a two-tailed significance of <0.05 were considered as good correlation between the standardized algometer and the tested techniques. RESULTS: There was a good inter-rater reliability (alpha C > 0.7) for the three techniques. There was a good correlation with r >0.65 (P < 0.001) between the measurements of standardized pressure algometer and the two techniques being tested as alternatives for algometer to measure pain. CONCLUSION: The sphygmomanometer cuff technique and electrical stimulation with the peripheral nerve stimulator to measure pain threshold and tolerance provide a simple, efficient, repeatable measure of pain intensity and can be used as suitable alternatives to standard algometers. PMID- 27006547 TI - Evaluation of postoperative pain scores following ultrasound guided transversus abdominis plane block versus local infiltration following day surgery laparoscopic cholecystectomy-retrospective study. AB - BACKGROUND AND AIMS: Postoperative pain for day surgery laparoscopic cholecystectomy has traditionally been managed with the surgeon infiltrating the wound with local anesthetic (LA). However, transversus abdominis plane (TAP) block has recently been used, although its superiority over LA remains uncertain. The primary aim was to compare LA and TAP block pain scores and analgesia used. The secondary aim was to assess satisfaction score and cost. MATERIAL AND METHODS: This retrospective study was commenced after ethics committee approval and ANZ clinical trial registry (ACTRN: 12612000737831). The data were collected from the theatre database and medical records of patients presenting for day case laparoscopic cholecystectomy. The sample included patients who received either bilateral port site LA infiltration with 20 ml of 0.25% Bupivacaine or bilateral TAP block with 20 ml of 0.5% ropivacaine and fentanyl postoperative pain protocol. The patients with incomplete medical records were excluded as were those admitted to an inpatient ward. Demographics and clinical characteristics were obtained from the hospital record along with pain score and postsurgery analgesia use. Postoperative pain satisfaction scores were collected by telephonic interview 30-180 days postsurgery. RESULTS: Of 51 patients analyzed, 19 were in TAP group 29 in LA group. There were no significant differences between the LA and TAP groups with respect to postoperative pain scores (P = 0.31) or patient satisfaction scores (1 and 2+) (P = 0.36). However, fentanyl consumption in the recovery room was significantly lower in TAP group (P = 0.0079.). The consumables cost were >3 times higher in the TAP when compared to LA group. CONCLUSION: The performance of the TAP block with respect to pain management was comparable to LA. However, LA remains more cost effective. PMID- 27006548 TI - No difference in pain reduction after epidural steroid injections in diabetic versus nondiabetic patients: A retrospective cohort study. AB - BACKGROUND AND AIMS: Diabetes affects peripheral and central neurons causing paresthesia, allodynia, hyperalgesia, and spontaneous pain. However, the effect of diabetes on response to epidural steroid injection (ESI) remains unknown. We hypothesized that diabetic patients receiving ESI will have different pain scores compared to nondiabetic patients. We tested a secondary hypothesis that pain reduction differs at different levels of hemoglobin A1c (HbA1c) for patients with diabetes. MATERIAL AND METHODS: Data from 284 consecutive patients given ESIs for radiculopathy were obtained via a manual review of electronic medical records. We initially compared diabetic and nondiabetic groups with respect to balance on baseline demographic and morphometric characteristics. Next, a linear regression model was developed to evaluate the association between existing diabetes and postinjection reduction in pain scores. And finally, we univariably characterized the association between HbA1c and pain reduction. RESULTS: After exclusion of nine patients, 275 patients were analysed, including 55 (20%) who were diabetic. Pain reduction after ESI was comparable in diabetic and nondiabetic patients (Wald test P = 0.61). The degree of pain reduction generally decreased with the level of HbA1c until reaching HbA1c levels of approximately 7.5%, after which point it stayed fairly constant. CONCLUSION: There was no difference in pain reduction after ESIs comparing diabetic with nondiabetic patients; however, for diabetic patients, pain reduction may decrease with uncontrolled diabetes determined by high HbA1c values, thus suggesting pain physicians to take an active role in guiding their patients to have their blood glucose levels better regulated to improve outcomes of their ESIs. PMID- 27006549 TI - Efficacy of tramadol and butorphanol pretreatment in reducing pain on propofol injection: A placebo-controlled randomized study. AB - BACKGROUND AND AIMS: Pain of propofol injection has been recalled by many patients as the most painful part of the induction of anesthesia. Tramadol and butorphanol are commonly used analgesics for perioperative analgesia in anesthesia practice. However, their potential to relieve propofol injection pain still needs to be explored. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled study was conducted on 90 American Society of Anesthesiologists I and II adult patients undergoing elective surgery under general anesthesia with propofol as an induction agent. Consecutive sampling technique with random assignment was used to allocate three groups of 30 patients each. Group I patients received an injection of normal saline 3 ml intravenously (placebo) while Group II and Group III patients received injection of tramadol 50 mg and butorphanol 1 mg intravenously, respectively. Before induction of anesthesia patients were asked about the intensity of pain on propofol injection by using visual analog scale (VAS) before the loss of consciousness. Descriptive statistics and analysis of variance with Chi-square test were used to analyze the data. The value of P < 0.05 was considered as a significant and P < 0.0001 as highly significant. RESULTS: The incidence of pain in Group I was observed in 80% of the patients, while it was observed in 23.33% and 20% of patients in Group II and III, respectively. Mean VAS scores were 2.27 +/- 1.51, 1.14 +/- 1.74, and 1.03 +/- 1.72 in Group I, II, and Group III patients, respectively. The incidence of pruritus was 10% and 6.7% and erythema in 13.2% and 6.7% in Group II and III, respectively. CONCLUSION: Pretreatment with both butorphanol and tramadol significantly reduced pain on propofol injection; however, they exhibited comparable efficacy among each other. Thus, either of these two drugs can be considered for pretreatment to reduce propofol injection pain. PMID- 27006550 TI - Patient refusal for regional anesthesia in elderly orthopedic population: A cross sectional survey at a tertiary care hospital. AB - BACKGROUND AND AIMS: Improvements in pain management techniques in the last decade have had a major impact on the practice of orthopedic surgeries, for example, total hip arthroplasty and total knee arthroplasty. Although there are a number of treatment options for postoperative pain, a gold standard has not been established. In our institution, both general anesthesia and regional anesthesia (RA), are being offered to the elderly orthopedic population but RA is not frequently accepted by elderly population. The objective of this study was to determine the frequency of various reasons for refusal of RA in elderly patients undergoing orthopedic surgeries. MATERIAL AND METHODS: A prospective study conducted over a period of 1 year, had 549 patients with ages above 60 years who underwent different types of elective orthopedic procedures 182 patients who refused RA were interviewed according to a structured questionnaire designed to assess the reasons of refusal. RESULTS: Most common reason for the refusal of RA was surgeon's choice (38.5%), whereas 20.3% of the patients were unaware about the RA. There was a significant association between female gender and refusing RA due to backache (17.2%) and fear of being awake during the operation (24.1%) respectively. CONCLUSION: This survey showed that the main reasons among elderly female population were the fear of remaining awake and backache. However, overall it was the surgeon's choice which made patients refuse RA, and the anesthesiologists were the main source of information. PMID- 27006551 TI - Laryngoscope decontamination techniques: A survey. AB - BACKGROUND AND AIMS: India is a vast country with variable, nonuniform healthcare practices. A laryngoscope is an important tool during general anesthesia and resuscitation. The study aimed to determine the current practices of laryngoscope decontamination in India. MATERIAL AND METHODS: An online survey was conducted amongst 100 anesthesiologists to determine the common methods of laryngoscope decontamination adopted in their settings. The survey was done over 6 months after validating the questionnaire. RESULTS: A total of 73 responses were received out of 100. The result of the survey revealed that there is no uniform technique of laryngoscope decontamination. There is marked variability in techniques followed not only among different institutions, but also within the same institution. CONCLUSION: There are no fixed protocols adopted for laryngoscope decontamination. Thus, there is a need to develop definitive guidelines on this subject, which can be implemented in India. PMID- 27006552 TI - Perioperative management of a patient with left ventricular dysfunction and anomalous coronary arteries. AB - Anesthetic management of patients with coronary artery disease undergoing noncardiac surgery is quite challenging. Such patients are at increased risk of perioperative cardiac complications and death. We report an illustrative case of a 62-year-old male with ischemic heart disease and anomalous coronary arteries for obstructed paraumbilical hernia repair. PMID- 27006553 TI - Incidental finding of tracheal bronchus complicating the anesthetic management of a left video-assisted thoracoscopic procedure. AB - Congenital abnormalities of the large airways are uncommon, but may occasionally pose significant difficulties for anesthesiologists. The tracheal bronchus is an anatomical variant in which an accessory bronchus originates directly from the trachea rather than distal to the carina, as a takeoff from the right mainstem bronchus. Anesthesiologists should be aware of this uncommon anomaly, its different variants, and its management in order to successfully establish one lung ventilation (OLV) for surgical isolation. In this article, we report the challenges encountered in establishing OLV in a patient with a previously undiagnosed aberrant right upper lobe bronchus arising directly from the trachea. PMID- 27006554 TI - Airway fires during surgery: Management and prevention. AB - Airway fires pose a serious risk to surgical patients. Fires during surgery have been reported for many years with flammable anesthetic agents being the main culprits in the past. Association of airway fires with laser surgery is well recognized, but there are reports of endotracheal tube fires ignited by electrocautery during pharyngeal surgery or tracheostomy or both. This uncommon complication has potentially grave consequences. While airway fires are relatively uncommon occurrences, they are very serious and can often be fatal. Success in preventing such events requires a thorough understanding of the components leading to a fire (fuel, oxidizer, and ignition source), as well as good communication between all members present to appropriately manage the fire and ensure patient safety. We present a case of fire in the airway during routine adenotonsillectomy. We will review the causes, preventive measures, and brief management for airway fires. PMID- 27006556 TI - Anesthetic management of a patient with severe neck dystonia during MRI. PMID- 27006555 TI - Clinically relevant exaggerated pharmacodynamic response to dual antiplatelet therapy detected by Thromboelastogram((r)) Platelet MappingTM. AB - Dual antiplatelet therapy (DAPT) is the standard of care for primary and secondary prevention strategies in patients with coronary artery disease after stenting. Current guidelines recommend that DAPT be continued for 12 months in patients after receiving drug eluting stents. Approximately 5% of these patients will present within this 12-month period for noncardiac surgery. This case report describes a clinically relevant exaggerated pharmacodynamic response to DAPT detected by preoperative assessment of platelet function. Based on the clinical history and physical exam and subsequent lab results, a general anesthetic was performed rather than a spinal anesthetic and the surgical procedure was changed. An exaggerated pharmacodynamic response to DAPT poses its own set of risks (unexpected uncontrolled bleeding, epidural hematoma following neuraxial block placement) that point-of-care aggregation testing may decrease or mitigate by altering clinical decision making. If the clinical history and physical exam reveal possible platelet dysfunction in patients receiving DAPT, preoperative platelet function testing should be considered. PMID- 27006557 TI - Anesthesia workstation ventilator malfunction due to accidental misplacement of a nasogastric tube. PMID- 27006558 TI - An unusual case of subcutaneous emphysema without pneumothorax following brachial plexus block. PMID- 27006559 TI - Management of pituitary apoplexy. PMID- 27006560 TI - A case of malpositioned catheter via supraclavicular approach for subclavian vein cannulation: A rare technique revisited. PMID- 27006561 TI - Survey on neuromuscular management. PMID- 27006562 TI - When everything failed, glidescope prevailed. PMID- 27006563 TI - Extravasation of fluid in neck secondary to perforation of vein by venous catheter. PMID- 27006564 TI - In response to unanticipated cannot intubate situation due to difficult mouth opening. PMID- 27006565 TI - Anesthetic management in spontaneous esophageal rupture (Boerhaave's syndrome). PMID- 27006566 TI - An unusual cause for concealed hemorrhagic shock in the second trimester of pregnancy resulting in fetal demise. PMID- 27006567 TI - Fiber optic intubation of a neonate with Syngnathia under local anesthesia and sedation. PMID- 27006568 TI - Lignocaine jelly: A simple solution to intraoperative endotracheal tube cuff leak. PMID- 27006569 TI - Dual mode ventilation: Winning strategy in difficult-to-wean. PMID- 27006570 TI - Retraction: Intrathecal sufentanil versus fentanyl for lower limb surgeries: A randomized controlled trial. AB - [This retracts the article on p. 67 in vol. 27, PMID: 21804710.]. PMID- 27006571 TI - Highlights in mechanisms and therapies for gastrointestinal and hepatic diseases: 1996 Shanghai International Gastroenterology Conference. PMID- 27006572 TI - Uptake of bacterial lipopolysaccharide and expression of tumor necrosis factor alpha-mRNA in isolated rat intrahepatic bile duct epithelial cells. AB - AIM: To study the uptake of bacterial lipopolysaccharides (LPS) and expression of tumor necrosis factor alpha-mRNA (TNF-alpha-mRNA) with cultured rat intrahepatic bile duct epithelial cells. METHODS: By using fluorescent, immunohistochemical and in situ hybridization techniques, the uptake of Escherichia coli LPS and expression of TNF-alpha-mRNA with isolated rat intrahepatic bile duct epithelial cells were observed with confocal laser scanning microscopy. RESULTS: Positive reactions to LPS were found in the cytoplasm of isolated intrahepatic bile duct epithelial cells after incubation with LPS for 15 min and the FITC fluorescent intensity against LPS was significantly higher than that of the controls (121.45 MUFI/MUm(2) +/- 15.62 MUFI/MUm(2) vs 32.12 MUFI/MUm(2) +/- 9.64 MUFI/MUm(2), P < 0.01). After incubation with LPS for 3 h, fluorescein isocyanate (FITC) fluorescent intensities of the expression of TNF-alpha-mRNA with fluorescent in situ hybridization in the cytoplasm and nuclei of the cultured bile duct epithelial cells were significantly higher than those of the controls (189.15 MUFI/MUm(2) +/- 21.33 MUFI/MUm(2) vs 10.00 MUFI/MUm(2) +/- 8.99 MUFI/MUm(2), 64.85 MUFI/MUm(2) +/- 14.99 MUFI/MUm(2) vs 21.20 MUFI/MUm(2) +/- 2.04 MUFI/MUm(2), respectively (P < 0.01)). The increase of FITC fluorescent intensity of TNF-alpha-mRNA expression in the cytoplasm peaked at 6 h after incubation (221.38 MUFI/MUm(2) +/- 22.99 MUFI/MUm(2)). At various time points after incubation with LPS, the increase of fluorescent intensities of TNF-alpha-mRNA in the cytoplasm were much higher than those in the nuclei (P < 0.01). CONCLUSION: LPS can act on and enter into isolated intrahepatic bile duct epithelial cells and stimulate the expression of TNF-alpha-mRNA. PMID- 27006573 TI - Effects of gamma-interferon on hepatic fibrosis of schistosoma japonicum-infected mice. AB - AIM: To probe the effect of gamma-IFN on hepatic fibrosis in schistosomiasis japonica. METHODS: The amount and distribution of gamma-IFN and extracellular matrix in the liver of 60 S. japonicum infected mice and 30 healthy mice at different stages, and their dynamics in 20 infected mice after administration of recombinant gamma-interferon were determined by immunohistochemical streptavidin biotin peroxidase complex method. RESULTS: The amount of gamma-IFN in liver peaked at the 16(th) week after infection (3 mice respectively reached 2+, 3+ and 4+ grade), which was higher than the levels of infected mice at the 8(th)-12(th) week (P < 0.01), and gamma-IFN was mostly distributed around egg granuloma. Fibronectin, laminin, type I and III collagens in liver of most infected mice reached 1+ grade and individual 2+ grade at the 8(th) week after infection, which were higher than those of healthy controls (P < 0.01), and were linearly distributed around egg granuloma . With chronicity and decrease of gamma interferon, however, the matrix proteins and collagens gradually increased, peaked respectively at the 20(th) and 24(th) week (over 70% infected mice with 3+ to 4+ grade), became wide and thick, and deposited in band like or retiform shape around and in egg granuloma. After administration of gamma-IFN, only 3 infected mice had 2+ grade of fibronectin at the 20(th) week, and 2 mice had 3+ grade of type III collagen at the 24(th) week, and none of them reached 4+ grade, which were significantly less than the untreated group at the same stage (P < 0.01 0.05). CONCLUSION: gamma-interferon may play an important role in opposing the inflammatory response of egg granuloma, decreasing secretion and deposition of extracellular matrix in the liver and suppressing hepatic fibrosis. PMID- 27006574 TI - Construction of retroviral vector carrying HSV-tk gene under control of human AFP enhancer core sequence and human pgk promotor. AB - AIM: To construct retroviral vector bringing HSV-tk gene under control of human AFP enhancer core sequence and human pgk promoter. METHODS: Internal SV40 promoter was deleted by SalI from retroviral vector pMNSM to construct pMNM. HSV tk gene driven by pgk promoter was released by BamH I from an eukaryotic expression vector pBPGK-tk, and inserted into polylinker site of pMNM to construct pMNP-tk retroviral vector. Human alpha-fetoprotein gene enhancer core sequence was released by EcoR I from pGEM. 7Z-AFPe plasmid was inserted into the immediate upstream of pgk promoter of pMNP-tk vector. Construction of hepatoma specific retroviral vector pMNAP-tk was completed. RESULTS: The structure of pMNP tk and pMNAP-tk vector was confirmed by restriction analysis. CONCLUSION: The vector is of great significance for hepatoma specific prodrug transformation gene therapy. PMID- 27006575 TI - Sequencing of hepatitis C virus cDNA with polymerase chain reaction directed sequencing. AB - AIM: To explore a rapid and easy sequencing method for hepatitis C virus (HCV) genome and establish a new sequencing method in China. METHODS: Polymerase chain reaction (PCR) was combined with a DNA sequencing technique. PCR products were purified by agarose gel electrophoresis, polyacrylamide gel electrophoresis (PAGE) and polyethylene glycol (PEG) respectively. Then, in the presence of a 5' labeling PCR primer, purified PCR products were directly sequenced. By this method, HCV NS5b cDNA from two HCV infected individuals (HC-42 and HC-49) were sequenced. RESULTS: PCR directed sequencing worked best using PCR amplified DNA purified by electrophoresis as a sequencing template. When sequencing a large number of templates, the purification step can be bypassed by using a lower concentration of dNTPs (40 MUmol of each dNTP) and primers (10 pmol of each primer) in the first stage of PCR. The aliquot of the first stage of PCR mixture was then directly used for amplification of chain terminated products but the sequencing ladders generated were of low intensity. Polyethylene glycol (PEG) could not remove nonspecific products of PCR, which affected the sequencing result to a certain extent and generated a background in sequencing ladders. Compared with the reported HCVJ and HC-C2, a new three nucleotide deletion was found in HC-42. CONCLUSION: PCR directed sequencing is a rapid, simple and effective method, especially for sequencing large samples. A three nucleotide deletion was first reported. PMID- 27006576 TI - Inhibitory effect of sulindac against chemically-induced primary colonic tumors by N-methyl-N-nitrosourea in mice. AB - AIM: To investigate the chemopreventive effect of sulindac, a nonsteroidal anti inflammatory drug (NSAID), on the growth of N-methyl-N-nitrosourea (MNU)-induced mouse colonic tumors. METHODS: The experimental colonic tumor model induced by intrarectal instillation of MNU in mice was used in the present study. In the first experiment, MNU intrarectal was instilled and sulindac administered concurrently to a group of mice for a period of 18 wk, while a control group of animals received MNU only for the same period. In the second experiment, two groups of mice that had already been treated with MNU for 12 wk received sulindac or not for another 18 wk. RESULTS: The tumors induced in mice were all located in the distal part of the large intestine. There were no significant differences in the location and the gross appearance of the tumors in the MNU-induced group and control group in both experiments. In the first experiment, sulindac caused a significant reduction in both the number of mice with colonic tumors and the number of tumors per mouse. Sulindac had a significant inhibitory effect on the growth of the MNU-induced tumors. However, in the second experiment, the inhibitory effect of sulindac was less or disappeared. CONCLUSION: Sulindac has a protective effect against the chemical induction of colonic tumors by MNU in mice. The chemopreventive effect is more significant in the initial stage of the tumor, while in the promotion stage this effect is less or disappeared. Sulindac can not cause the regression of established tumors. PMID- 27006577 TI - Studies on the relationship between the point mutation of ras oncogenes and the prognosis of patients with gastric cancer. AB - AIM: To study the relationship between the point mutation of ras oncogenes and the prognosis of patients with gastric cancer. METHODS: The point mutations at codon 12 and 61 of c-Ha-ras, at codon 12 and 13 of K-ras, and at codon 12 of N ras were studied with PCR-RFLP in 88 formalin fixed and paraffin embedded specimens of gastric cancer. RESULTS: It was found that the overall rate of point mutation of ras oncogenes was 18.2% and the positivity of the point mutation of ras oncogenes was related to the cancerous invasion of the serosa, the status of lymph node metastasis, the stage of cancer and the survival time after surgery. CONCLUSION: The findings suggest that the determination of point mutations of ras oncogenes can be used to determine the prognosis of patients with gastric cancer. PMID- 27006578 TI - Cellular immune function and liver damage in post-hepatitic cirrhosis. AB - AIM: To study cellular immune function in patients with post-hepatitic cirrhosis (PHC) and its relationship with different types of liver damage. METHODS: Fifty one patients with PHC, including 20 cases of Child-Pugh class A, 18 of class B, 13 of class C and 22 normal subjects as controls were studied. After peripheral blood mononuclear cells were isolated by Ficoll-Hypaque gradient centrifugation, lymphocyte transformation (LT) test, IL-2 activity and NK cell activity were measured by the (3)H-TdR incorporation technique. RESULTS: Changes of LT stimulation index (SI), IL-2 activity (SI) and NK cell activity (%) in patients with PHC were significantly decreased compared with in the healthy controls (18.1 +/- 13.0 vs 34.9 +/- 21.7, P < 0.01; 8.1 +/- 6.0 vs 13.6 +/- 5.8, P < 0.01; 40.3 +/- 21.7 vs 61.3 +/- 20.5, P < 0.01; respectively). The defects of cellular immune function were closely related to Child-Pugh classification. The values in class C were much lower than those in B and A (P < 0.01) and those in B were lower than those in A (P < 0.05). CONCLUSION: Defective cellular immune functions in patients with PHC are connected with the degree of liver damage. PMID- 27006579 TI - Surgical treatment of biliary ductal stricture complicating localized left hepatolithiasis. AB - AIM: To summarize the experience in the clinical treatment of biliary duct strictures complicating localized left hepatolithiasis in the last two decades. METHODS: A retrospective analysis of 67 cases of biliary duct strictures complicating localized left hepatolithiasis treated in our center in the last two decades was made with regards to each patient's age, gender, results of various preoperative examinations, operative findings, treatment and postoperative courses. RESULTS: The incidence of left hepatic duct (LHD) stricture was 59.8% and that of a left external hepatic duct (LEHD) stricture was 84.0 % and 84.8% respectively, in which a severe degree dominated. Among the operative procedures used in the treatment of LHD strictures, plastic operation plus biliary enteric anastomosis ranks first in frequency (52.2%), with a re-stricture rate of 17.1%. Left lobectomy ranks third (19.4%) with no re-stricture. Simple plastic performance or dilation had a high occurrence rate of re-stricture and usually needed subsequent surgery. Most LEHD strictures were eradicated by lateral segmentectomy or lobectomy, whereas most LMHD strictures were just the opposite. The rate of preoperative diagnosis of LMHD by endoscopic retrograde cholangiography, percutaneous transhepatic cholangiography, computed tomography or intraoperative and postoperative trans-T-tube cholangiography was much lower than that of LEHD or extrahepatic duct. CONCLUSION: Too much attention paid to LEHD disorders in the treatment of localized left hepatolithiasis potentially results in negligence or omission in LMHD disorders. Malpractice treatments of LHD strictures are important factors affecting the long term results of localized left hepatolithiasis, for which left lobectomy is usually the therapy of choice. PMID- 27006580 TI - Study of the influence of hiatus hernia on gastroesophageal reflux. AB - AIM: To explore whether the presence of a sliding hiatus hernia influences gastroesophageal reflux. METHODS: Endoscopy and 24 h pH monitoring were performed for 197 outpatients with gastroesophageal reflux symptoms. RESULTS: Of the 197 patients with symptoms of gastroesophageal reflux, patients with hiatus hernia accounted for 36%. The incidence of esophagitis in patients with hiatus hernia was significantly higher than that in patients without hiatus hernia. The results of 24 h pH monitoring showed that 84 patients had physiological reflux, 37 had pathological reflux without esophagitis, 64 had reflux esophagitis and 12 had physiological reflux concomitant with esophagitis. All the patients with hiatus hernia had a longer percentage time with supine reflux and a higher frequency of episodes lasting over 5 min at night compared to those without hiatus hernia. The incidence of combined daytime and nocturnal reflux in patients with hiatus hernia was significantly higher than that in patients without hiatus hernia. CONCLUSION: Pathological reflux and reflux esophagitis in some patients with symptoms of gastroesophageal reflux represent two different stages of gastroesophageal reflux disease. Pathological reflux is the first stage, in which the lower esophageal sphincter is incompetent but the esophageal mucosal resistance effectively prevents regurgitated acid from damaging the esophageal mucosa. Reflux esophagitis represents the second stage, in which the aggression of the regurgitated acid is so strong that the esophageal mucosa fails to resist it and the epithelium of the esophagus is damaged. Patients with hiatus hernia have a high incidence of combined daytime and nocturnal reflux, with the latter being responsible for esophagitis. PMID- 27006582 TI - Adherent properties of Helicobacter pylori to human epithelial cells. AB - AIM: To study the properties and factors of Helicobacter pylori (H. pylori) adherence to human epithelial cells. METHODS: The adherent properties of human epithelial cells were studied using a group of isolated H. pylori strains, anti H. pylori monoclonal antibodies and varied pH environment in in vitro adherence model with HEp2 cells. RESULTS: H. pylori YC 11A was able to adhere to HEp2 cells specifically and its adherence efficiency reached the highest (81%) within 3 h after incubation with HEp2 cells. There was no significant difference between adherence in air and in 5% oxygen. The monoclonal antibodies specific to H. pylori predominant antigens did not inhibit activities on adherence of H. pylori to HEp2 cells. The pH value significantly affected the adherence process and the optimal pH was 3.0-4.6. CONCLUSION: H. pylori specifically adheres to HEp2 cells, and pH value significantly affects this process. A high level of anti-H. pylori predominant antibodies in serum may have no protective activities against H. pylori infection. PMID- 27006581 TI - Reduced secretion of epidermal growth factor in duodenal ulcer patients with Helicobacter pylori infection. AB - AIM: To investigate the concentration changes of epidermal growth factor (EGF) in duodenal ulcer patients with Helicobacter pylori (H. pylori) infection. METHODS: Immunoreactive concentration of somatostatin, gastrin and epidermal growth factor of gastric and saliva juice in healthy volunteers, and chronic gastritis and duodenal ulcer patients with H. pylori infection were measured by radioimmunoassay. RESULTS: Gastrin concentration of gastric juice in H. pylori positive chronic gastritis (P > 0.05) and duodenal ulcer patients (P < 0.01) was higher than that of healthy volunteers (P < 0.05), whereas som atostatin concentration of gastric juice in chronic gastritis (P < 0.05) and duodenal ulcer patients (P < 0.01) was lower than that in healthy volunteers. Furthermore, EGF levels of gastric and saliva juice in duodenal ulcer patients with H. pylori infection (n = 10, 272.0 ng/L +/- 96.3 ng/L and 8.3 ng/L +/- 2.4 ng/L, respectively) were significantly lower than that in healthy volunteers (n = 12, 405.6 ng/L +/- 35.6 ng/mL and 22.0 ng/L +/- 17.0 ng/L, respectively) and in H. pylori-positive chronic gastritis patients (n = 25, 423.0 ng/L +/- 104.0 ng/L and 22.0 ng/L +/- 11.1 ng/L, respectively (P < 0.05). CONCLUSION: A lower secretion of EGF may be a causative factor in the pathogenesis of H. pylori-positive duodenal ulcer. PMID- 27006583 TI - Evaluation of a fecal occult blood test with reverse passive hemagglutination for colorectal neoplasm screening. AB - AIM: To evaluate the one and three sampling reverse passive hemagglutination fecal occult blood test (RPHA FOBT) for colorectal neoplasm screening. METHODS: A group of 3034 individuals with histories of colorectal polyps and/or ulcers were screened for colorectal cancer. Three day fecal samples were collected and 60 cm fiberoptic colonoscopy was conducted for each subject. The fecal samples were tested for occult blood with the RPHA method and the endoscopic and histopathological diagnoses were used as standard reference for evaluation. The sensitivity, specificity and positive and negative predictive values of different samplings were compared. RESULTS: About 521 cases of colorectal neoplasms were detected, including 12 cases of colorectal cancer and 509 cases of polyps. Results showed that the mean sensitivity of one sampling RPHA FOBT for colorectal neoplasm was only 13.2%, the specificity was 90.3% and the positive and negative predictive values were 21.3% and 83.4%, respectively; while for the three sampling, taking one positivity as positive, the sensitivity increased to 22.0%, the specificity decreased to 81.6% and the positive and negative predictive values were 19.7% and 83.6%, respectively. CONCLUSION: A single RPHA FOBT seems to be less sensitive for screening for colorectal neoplasms. Since it is convenient and economical, RPHA FOBT remains the most practical procedure for detection of early colorectal cancer and polyps if it is combined with other screening methods. PMID- 27006584 TI - Analysis of lactate dehydrogenase activities and isoenzyme patterns in colorectal cancer tissues. AB - AIM: To investigate the relationship between lactate dehydrogenase (LDH) activity or LDH isoenzyme patterns and the pathogenesis of colorectal cancer. METHODS: Activities of tissue LDH and LDH isoenzyme patterns in 16 patients with colorectal cancer were assayed using spectrophotometric procedures and agarose gel electrophoresis, respectively. RESULTS: The total and specific activities of LDH were significantly higher in colorectal cancer tissues than those in adjacent noncancerous tissues (P < 0.001). The LDH isoenzyme pattern was also different from that in the control. The percentage of LDH5 doubled and the ratio of LDH4 + LDH5/LDH1 + LDH2 was 3.6 +/- 1.4 in cancer tissue, significantly greater than in the control. CONCLUSIONS: The increased LDH activity in colorectal cancer tissues resulted mainly from the increased LDH5, suggesting that the alteration of LDH activity and isoenzyme patterns were related to the pathogenesis of colorectal cancer. PMID- 27006585 TI - Clinical observation of (125)I-labeled anti-alpha fetoprotein antibody radioimmunotherapy in hepatocellular carcinoma. AB - AIM: To observe the therapeutic effects and toxic side effects of (125)I labeled horse anti-human alpha fetoprotein (AFP) polyclonal antibodies in immune targeted therapy against hepatocellular carcinoma (HCC). METHODS: A modified chloramine-T method to produce nuclide (125)I labeled horse anti-human AFP polyclonal antibodies was used to treat 22 cases of HCC. Drugs were administered by intravenous drip. The median dose of (125)I in the whole group was 289.3 (100.3 708.9) MBq. In this series of 22 cases, 19 were evaluated. HCC cases of the same period treated by (131)I anti AFP (A group), anti-cancer drugs and anti AFP conjugates (B group) and chemotherapy alone (C group) were used as controls. RESULTS: The effective rate (CR + PR) was 31.6%, tumor shrinkage rate was 63.2% (12/19), AFP descending rate 64.7% (11/17) and 6 cases became AFP negative. The post treatment 1 year survival rate was 47.1% (8/17). Seven cases are still alive. Five cases survived 14.33 mo, showing good therapeutic tolerance and minimal toxic side effects. CONCLUSION: The therapeutic effect in the treatment group was significantly better than that of the control groups. This may be due to the effect of the continuous radiation of the long half life (125)I within the tumor cells. PMID- 27006586 TI - Drinking water and liver cancer. AB - AIM: To study the relationship between the mutagenicity of drinking water and incidence of liver cancer in high liver cancer incidence areas in Guangxi. METHODS: A relationship between the mutagenicity of drinking water and incidence of liver cancer was studied in Fusui County, a high liver cancer incidence area in China. Thirty-two samples of different kinds of drinking water (13 samples of pond water, 3 samples of well water near the ponds, 5 samples of well water, 6 samples of river water and 5 samples of tap water) were tested with a micronuclear technique in the root tips of Vicia faba. RESULTS: Among the 32 samples of different kinds of drinking water, 12 samples of pond water and 2 samples of well water near the ponds induced micronucleus frequencies on the root tips of Vicia faba to increase (P < 0.01), with the average micronucleus rate being 15.8% and 11.7%, respectively, while there was no difference between the micronucleus frequencies on the root tips of Vicia faba induced by well water (4.3%), river water (3.9%) or tap water (4.2%) and that on the control group (P > 0.05). Micronuclear effects on the root tips of Vicia faba in different kinds of drinking water were positively related to the incidence of liver cancer (r = 0.86, P < 0.05). CONCLUSION: There were substances that caused chromosomal aberrations in the drinking pond water in high liver cancer incidence areas of Guangxi. Different kinds of drinking water were closely related to the incidence of liver cancer. Chemical mutagens in the water may be an important factor in the high incidence of human liver cancer. PMID- 27006587 TI - Co-regulative effects of the cAMP/PKA and DAG/PKC signal pathways on human gastric cancer cells during differentiation induced by traditional Chinese medicines. AB - AIM: To evaluate the role of cAMP/PKA and DAG/PKC pathways of MGc80-3 cells treated with a traditional Chinese medicine compound, bailong preparation (bailong). METHODS: cAMP level, DAG content and activities of PKA and PKC were measured in different groups: control; 1.8 g/L bailong; 1.8 g/L bailong + 20 mg/L PKA inhibitor; and 5 MUmol/L PKC inhibitor. RESULTS: When MGc80-3 cells were treated with bailong for 3 h, cAMP level and PKA activity were 113% and 19.7% higher than those of the control, while DAG content and PKC activity were 47.0% and 64.2% lower than those of the control. When the PKC pathway was blocked by PKC inhibitor GF-109203 X, cAMP level and PKA activity were increased by 78.8% and 33.5% compared to inhibitor GF-109203 X, and cAMP level and PKA activity were increased by 78.8% and 33.5% compared to the control, while the DAG content and PKC activity were decreased by 40.3% and 56.3%. When MGc80-3 cells were treated with bailong and PKA inhibitor blocked PKA pathways at the same time, cAMP level and PKA activity were decreased by 46.0% and 28.9%. On the other hand, DAG content and PKC activity were increased by 50.7% and 51.6% compared to the bailong group. CONCLUSION: There is a relationship of cause and effect between differentiation of MGc80-3 cells and the signal pathways. The results of this study are similar to that of hexamethylenebisacetamide (HMBA), suggesting that the two signal systems are the foundation of proliferative regulation of MGc80-3 cells treated with Chinese medicine bailong or HMBA. PMID- 27006588 TI - Study of the regulatory effect of acupuncture on rotation-induced gastric dysrhythmia in rabbits. AB - AIM: A model of experimental gastric dysrhythmia in rabbits was set up to evaluate the effect of different acupoints on regulating gastric dysrhythmia in rabbits so as to promote acupuncture treatment for this kind of disease. METHODS: A model of gastric dysrhythmia in rabbits was established by the rotation method using the basic electrical rhythm (BER) as an objective index. After puncturing at the points of Zusanli (ST36), Neiguan (PC6), Tiaokou (ST38) and Tianquan (PC2) in the four groups of experimental gastric dysrhythmia rabbits, the difference in regulatory effects on the disturbance and frequency of the gastric electric slow wave was observed. RESULTS: Before needling at the specific acupoints Zusanli and Neiguan, the percentage of disturbance electric slow wave for the Zusanli and Neiguan groups was 57.0785 +/- 10.644 and 55.5173 +/- 6.0500, respectively; after such needling, the percentage was 43.7823 +/- 10.1518 and 43.5147 +/- 6.8983 for the Zusanli and Neiguan groups, respectively, while the frequency of electric slow wave for the Zusanli and Neiguan groups was 2.2870 +/- 0.3800 and 2.4020 +/- 0.3536, respectively, before needling and after needling, the frequency was 2.7090 +/- 0.5865 and 2.9220 +/- 0.4923 for the Zusanli and Neiguan groups, respectively. Comparing the percentage and frequency for the Zusanli and Neiguan groups before and after needling, the result shows that both groups have a significant difference statistically (P < 0.05) but between the Zusanli and Neiguan groups, there was no significant difference. Before and after needling the nonspecific acupoints of Tiaokou and Tianquan, there was no difference between the Tiaokou and Tianquan groups. Between the Zusanli and Tiaokou groups and the Neiguan and Tianquan groups, there are significant differences in regulating gastric dysrhythmia. CONCLUSION: This model is suitable for the observation of gastric dysrhythmia. The specific acupoints of Zusanli and Neiguan have good effects on the treatment of gastric dysrhythmia. PMID- 27006589 TI - Current status of basic and clinical research in the field of gastroenterology in China. PMID- 27006590 TI - Improved Bowel Preparation with Multimedia Education in a Predominantly African American Population: A Randomized Study. AB - Background and Aim. Inadequate bowel preparation is a major impediment in colonoscopy quality outcomes. Aim of this study was to evaluate the role of multimedia education (MME) in improving bowel preparation quality and adenoma detection rate. Methods. This was an IRB-approved prospective randomized study that enrolled 111 adult patients undergoing outpatient screening or surveillance colonoscopy. After receiving standard colonoscopy instructions, the patients were randomized into MME group (n = 48) and control group (n = 46). The MME group received comprehensive multimedia education including an audio-visual program, a visual aid, and a brochure. Demographics, quality of bowel preparation, and colonoscopy findings were recorded. Results. MME group had a significantly better bowel preparation in the entire colon (OR 2.65, 95% CI 1.16-6.09) and on the right side of the colon (OR 2.74, 95% CI 1.12-6.71) as compared to control group (p < 0.05). Large polyps (>1 cm) were found more frequently in the MME group (11/31, 35.5% versus 0/13; p < 0.05). More polyps and adenomas were detected in MME group (57 versus 39 and 31 versus 13, resp.) but the difference failed to reach statistical significance. Conclusion. MME can lead to significant improvement in the quality of bowel preparation and large adenoma detection in a predominantly African-American population. PMID- 27006593 TI - First record of the genus Dialarnaca Gorochov, 2005 from China, with description of two new species (Orthoptera, Gryllacrididae, Gryllacridinae). AB - In the present paper, Dialarnaca Gorochov, 2005 is recorded from China for the first time, with two new species of the genus described, Dialarnaca longicerca Shi & Bian, sp. n. and Dialarnaca zhoui Shi & Bian, sp. n. A key and a distribution map of the genus Dialarnaca, are provided. PMID- 27006591 TI - Identification of Potential Anticancer Activities of Novel Ganoderma lucidum Extracts Using Gene Expression and Pathway Network Analysis. AB - Ganoderma lucidum (lingzhi) has been used for the general promotion of health in Asia for many centuries. The common method of consumption is to boil lingzhi in water and then drink the liquid. In this study, we examined the potential anticancer activities of G. lucidum submerged in two commonly consumed forms of alcohol in East Asia: malt whiskey and rice wine. The anticancer effect of G. lucidum, using whiskey and rice wine-based extraction methods, has not been previously reported. The growth inhibition of G. lucidum whiskey and rice wine extracts on the prostate cancer cell lines, PC3 and DU145, was determined. Using Affymetrix gene expression assays, several biologically active pathways associated with the anticancer activities of G. lucidum extracts were identified. Using gene expression analysis (real-time polymerase chain reaction [RT-PCR]) and protein analysis (Western blotting), we confirmed the expression of key genes and their associated proteins that were initially identified with Affymetrix gene expression analysis. PMID- 27006594 TI - Beetle and plant arrow poisons of the Ju|'hoan and Hai||om San peoples of Namibia (Insecta, Coleoptera, Chrysomelidae; Plantae, Anacardiaceae, Apocynaceae, Burseraceae). AB - The use of archery to hunt appears relatively late in human history. It is poorly understood but the application of poisons to arrows to increase lethality must have occurred shortly after developing bow hunting methods; these early multi stage transitions represent cognitive shifts in human evolution. This paper is a synthesis of widely-scattered literature in anthropology, entomology, and chemistry, dealing with San ("Bushmen") arrow poisons. The term San (or Khoisan) covers many indigenous groups using so-called 'click languages' in southern Africa. Beetles are used for arrow poison by at least eight San groups and one non-San group. Fieldwork and interviews with Ju|'hoan and Hai||om hunters in Namibia revealed major differences in the nature and preparation of arrow poisons, bow and arrow construction, and poison antidote. Ju|'hoan hunters use leaf-beetle larvae of Diamphidia Gerstaecker and Polyclada Chevrolat (Chrysomelidae: Galerucinae: Alticini) collected from soil around the host plants Commiphora africana (A. Rich.) Engl. and Commiphora angolensis Engl. (Burseracaeae). In the Nyae Nyae area of Namibia, Ju|'hoan hunters use larvae of Diamphidia nigroornata Stahl. Larvae and adults live above-ground on the plants and eat leaves, but the San collect the underground cocoons to extract the mature larvae. Larval hemolymph is mixed with saliva and applied to arrows. Hai||om hunters boil the milky plant sap of Adenium bohemianum Schinz (Apocynaceae) to reduce it to a thick paste that is applied to their arrows. The socio-cultural, historical, and ecological contexts of the various San groups may determine differences in the sources and preparation of poisons, bow and arrow technology, hunting behaviors, poison potency, and perhaps antidotes. PMID- 27006595 TI - Systematic review of the firefly genus Scissicauda (Coleoptera, Lampyridae, Amydetinae) from Brazil. AB - The Amydetinae genus Scissicauda McDermott, 1964 is reviewed and redescribed. We describe Scissicauda balena sp. n. from Brazil as new, and provide illustrations of the structural features and a key to species of both sexes. PMID- 27006592 TI - Impact of Transfusion on Cancer Growth and Outcome. AB - For many years, transfusion of allogeneic red blood cells, platelet concentrates, and plasma units has been part of the standard therapeutic arsenal used along the surgical and nonsurgical treatment of patients with malignancies. Although the benefits of these blood products are not a matter of debate in specific pathological conditions associated with life-threatening low blood cell counts or bleeding, increasing clinical evidence is nevertheless suggesting that deliberate transfusion of these blood components may actually lead to negative clinical outcomes by affecting patient's immune defense, stimulating tumor growth, tethering, and dissemination. Rigorous preclinical and clinical studies are needed to dimension the clinical relevance, benefits, and risks of transfusion of blood components in cancer patients and understand the amplitude of problems. There is also a need to consider validating preparation methods of blood components for so far ignored biological markers, such as microparticles and biological response modifiers. Meanwhile, blood component transfusions should be regarded as a personalized medicine, taking into careful consideration the status and specificities of the patient, rather than as a routine hospital procedure. PMID- 27006597 TI - Three new species of Tricimba Lioy from the West Palaearctic region (Diptera, Chloropidae). AB - Tricimba rudolfi Kubik, sp. n. (Czech Republic, Portugal), Tricimba chalupi Kubik, sp. n. (Czech Republic), and Tricimba dursuni Kubik, sp. n. (Turkey) are described and illustrated. First records of Tricimba kaplanae Dely-Draskovits, 1983 from Corsica and Tricimba hungarica Dely-Draskovits, 1983 from Turkey are listed. PMID- 27006596 TI - Review of Afraustraloderes rassei Bouyer, 2012: description of its female and a new species of Pixodarus Fairmaire, 1887 (Coleoptera, Cerambycidae, Prioninae). AB - The original description of Afraustraloderes rassei Bouyer, 2012 included a female that is now recognized as a separate species belonging to the genus Pixodarus and here described as Pixodarus spiniscapus sp. n. The true female of Afraustraloderes rassei has also been obtained recently and is, therefore, here described. The synonymy of Pixodarus exasperatus with Pixodarus nyassae, proposed earlier by Santos Ferreira (1980), is here supported. Conversely, the earlier inclusion of Afraustraloderes rassei in the tribe Hopliderini is rejected, on the basis of a key set of characters established by Quentin and Villiers (1972, 1975). Afraustraloderes rassei appears to be restricted to the Cape Floral Region, exhibiting larval development in trunks and roots of dead Proteaceae plants. Conversely, Pixodarus spiniscapus has so far only been recorded in the eastern part of South Africa and appears to be associated with bushveld vegetation. PMID- 27006598 TI - Leinendera achaeta sp. n., a new species of robber fly from Brazil (Diptera, Asilidae, Asilinae). AB - The third species of the Neotropical genus Leinendera Carrera, 1945, Leinendera achaeta sp. n., is described from Rio Grande do Sul state, Brazil. The habitus, wing and male terminalia are described and illustrated, and a key to the three Brazilian species is provided. PMID- 27006599 TI - Faunistic and bibliographical inventory of the Psychodinae moth-flies of North Africa (Diptera, Psychodidae). AB - All published records for the 49 species of moth flies known from North Africa are reviewed and discussed: Morocco (27 species), Algeria (33 species), Tunisia (18 species) and Egypt (five species). In addition, records of seven species of Psychodinae new to the fauna of Morocco are added, of which three are new mentions for North Africa (Table 1) and one is a new record for Egypt. Telmatoscopus squamifer Tonnoir, 1922 is transferred to the genus Iranotelmatoscopus Jezek, 1987, comb. n. Satchelliella reghayana Boumezzough & Vaillant, 1987 is transferred to the genus Pneumia Enderlein, 1935, comb. n. Pneumia aberrans Tonnoir, 1922 is transferred to the subgenus Logima. PMID- 27006600 TI - A new species of Chaetaglaea (Lepidoptera, Noctuidae, Noctuinae, Xylenini), from eastern North America. AB - Chaetaglaea tremula (Harvey) occurs through the Gulf States, from southern Florida, west to eastern Texas. Coastal populations, previously referred to Chaetaglaea tremula occurring from the Carolinas, at least as far north as Massachusetts and shoreline dunes in southwestern Ontario are recognized as distinct and described here as Chaetaglaea rhonda. Adults and genitalia are illustrated for Chaetaglaea rhonda and Chaetaglaea tremula. PMID- 27006601 TI - On the spider genus Arboricaria with the description of a new species (Araneae, Gnaphosidae). AB - The spider genus Arboricaria Bosmans, 2000 is redefined and an updated diagnosis given. The differences between Arboricaria and Micaria Westring, 1851 are discussed in detail. A key to all five species of the genus is provided. One new species, Arboricaria zonsteini sp. n. (??), is described based on specimens from Kyrgyzstan and Azerbaijan. One new synonym is proposed: Arboricaria koeni Bosmans in Bosmans & Blick, 2000, syn. n. is assigned to Arboricaria sociabilis Kulczynski in Chyzer & Kulczynski, 1897. Data on the distribution of Arboricaria in Russia and adjacent countries are presented with references to the papers on local spider faunas. PMID- 27006602 TI - Two new species of Parapharyngodon parasites of Sceloporus pyrocephalus, with a key to the species found in Mexico (Nematoda, Pharyngodonidae). AB - Two new species of Parapharyngodon collected from the intestine of the Mexican boulder spiny lizard Sceloporus pyrocephalus are described. This study increases to 49 the number of valid species assigned to Parapharyngodon worldwide, 11 of them distributed in Mexico. Males of the two new species share the presence of four pairs of caudal papillae, an anterior echinate cloacal lip and the presence of lateral alae; however, both differ from each other in lateral alae extension and echinate cloacal anterior lip morphology. Females of both species have a prebulbar uterus and eggs shell punctuate with pores, characteristics shared with few other species of Parapharyngodon. Both new species differ from other congeneric species in the papillar arrangement, the anterior cloacal lip morphology, the lateral alae extension and total length/spicule ratio. A taxonomic key for the species of Parapharyngodon distributed in Mexico is provided. PMID- 27006603 TI - A new interstitial ostracod species of the genus Paracobanocythere from Vietnam, with mitochondrial CO1 sequence data of three Asian species. AB - This study is a first report of an interstitial ostracod from Southeast Asia. The ostracod species, Paracobanocythere vietnamensis sp. n., was found in the marine interstitial environment of Phu Quoc Island, Vietnam. Thus far, three species of this genus have been described. The morphology of the carapace as well as the appendages of this new species are quite similar to Paracobanocythere hawaiiensis and Paracobanocythere watanabei. However, we found that they could be easily distinguished according to the morphology of the male copulatory organ. Additionally, we estimated the evolutionary distances among these three species based on nucleotide and amino acid sequences of the mitochondrial CO1 gene. Similar morphologies of carapaces and appendages, and relatively small evolutionary distances according to CO1 between Paracobanocythere vietnamensis sp. n. and Paracobanocythere watanabei suggest that these two species are very closely related. PMID- 27006604 TI - A black-and-red stick insect from the Philippines - observations on the external anatomy and natural history of a new species of Orthomeria. AB - A new stick insect of the genus Orthomeria Kirby, 1904 (Phasmatodea, Aschiphasmatidae) is described from the Philippines. Orthomeria (Orthomeria) kangi sp. n. is readily distinguished from all other congeners by the distinctive blood red colouration of the costal region of the hind wings. Major features of the external morphology of adults, eggs, and first-instar nymphs are illustrated. Locomotory attachment pads are of the smooth type with irregular microgrooves on the contact surface. An unusual condition of male terminalia is the absence of tergal thorn pads on segment 10. The male clasping organs are represented by an elongated vomer terminating in a prominent spine, and by incurved cerci featuring a bilobed apex equipped with a sharp blade-like ridge. Intraspecific variation in body colouration and hind wing length occurs in females. The new species lives at 400-650 m elevation in the surroundings of the Sablang and Tuba regions, in the Benguet Province of Luzon island. Host plants include Ficus spp. (Moraceae), and Pipturus spp. and Leucosyke spp. (Urticaceae). Observations on the mating and defensive behaviour are presented. Orthomeria (Orthomeria) catadromus (Westwood, 1859) is recognised as a junior synonym of Orthomeria (Orthomeria) pandora (Westwood, 1859), syn. n. A lectotype is designated for both species. Finally, an updated identification key to the species of the subgenus Orthomeria is provided. PMID- 27006605 TI - Revision of Paranastatus Masi (Eupelmidae, Eupelminae) with descriptions of four new species. AB - Paranastatus Masi, 1917 (Eupelmidae, Eupelminae) was originally described based on two species from Seychelles: Paranastatus egregius and Paranastatus violaceus. Eady (1956) subsequently described Paranastatus nigriscutellatus and Paranastatus verticalis from Fiji. Here, four new species of Paranastatus are described: Paranastatus bellus Scallion, sp. n. and Paranastatus pilosus Scallion, sp. n. from Indonesia, and Paranastatus halko Scallion, sp. n. and Paranastatus parkeri Scallion, sp. n. from Fiji. A key to all Paranastatus species based on females is included and lectotypes are designated for Paranastatus egregius and Paranastatus violaceus. Finally, previously unobserved colour variation from newly collected material of Paranastatus verticalis, distribution patterns of species, and possibilities for future research are discussed. PMID- 27006606 TI - Revision of the subgenus Tinotus Sharp, stat. n., of the parasitoid rove-beetle genus Aleochara Gravenhorst (Coleoptera, Staphylinidae, Aleocharinae) from Japan, Taiwan, and the Russian Far East. AB - The subgenus Tinotus Sharp, 1833, stat. n., of the genus Aleochara Gravenhorst, 1802 (Aleocharini: Aleocharina) from Japan, Taiwan, and the Russian Far East is revised. Tinotus is a new record from the latter two regions. Three species are recognized: Aleochara (Tinotus) morion Gravenhorst, 1802, comb. n. [Japan (new record), the Russian Far East (new record)], Aleochara (Tinotus) eoa nom. n. [replacement name for Tinotus japonicus Cameron, 1933; Japan, Taiwan (new record)], and Aleochara (Tinotus) takashii sp. n. (central Honshu, Japan). The systematic position of Tinotus is discussed. All species are (re-)described, keyed, and figured. A world checklist of Tinotus species, comprising 40 valid species, is provided in an appendix. Additional taxonomic changes are proposed, including a new synonymy, a revalidation, 13 new replacement names, and 27 new combinations. PMID- 27006607 TI - Drusus sharrensis sp. n. (Trichoptera, Limnephilidae), a new species from Sharr National Park in Kosovo, with molecular and ecological notes. AB - In this paper we describe Drusus sharrensis sp. n., from the Sharr Mountains in Kosovo. Males of the new species are morphologically most similar to Drusus krusniki Malicky, 1981, Drusus kerek Olah, 2011 and Drusus juliae Olah, 2011 but differ mainly in exhibiting (1) a differently shaped spinose area on tergite VIII; (2) intermediate appendages anteriorly curved in lateral view with broad tips in dorsal view; (3) inferior appendages with a distinct dorsal protrusion in the proximal half. Females of the new species are morphologically most similar to Drusus krusniki, Drusus kerek, Drusus juliae, and Drusus plicatus Radovanovic, 1942 but mainly differ in (1) segment X that is longer than the supragenital plate with distinctly pointed tips; (2) supragenital plate quadrangular with a distinct round dorsal protrusion; (3) a vulvar scale with a small median lobe. Results of phylogenetic species delimitation support monophyly of Drusus sharrensis sp. n. and recover it as sister to a clade comprising (Drusus pelasgus Olah, 2010 + Drusus juliae + Drusus arbanios Olah, 2010 + Drusus plicatus + (Drusus dacothracus Olah, 2010 + Drusus illyricus Olah, 2010)). The new species is a micro-endemic of the Sharr Mountains, a main biodiversity hotspot in the Balkan Peninsula. Main threats to the aquatic ecosystems of this part of the Balkan Peninsula are discussed. PMID- 27006608 TI - Ectomyelois Heinrich, 1956 in China, with descriptions of two new species and a key (Lepidoptera, Pyralidae, Phycitinae). AB - Only three species belonging to the genus Ectomyelois Heinrich, 1956 are recorded from China, of which two species, Ectomyelois bipectinalis sp. n. and Ectomyelois furvivena sp. n. are described as new. We discuss the status of Ectomyelois that has been treated as a junior synonym by previous authors; we treat it as a valid genus, revised status, based on characters of the venation and female genitalia. Photographs of the adults and illustrations of the genitalia are given, along with a key to the three known Chinese species. PMID- 27006609 TI - Two new and one newly recorded species of Gracillariidae from China (Lepidoptera). AB - The paper presents four Chinese species belonging to the genera Metriochroa Busck, Eumetriochroa Kumata, and Gibbovalva Kumata & Kuroko (Lepidoptera, Gracillariidae), including two new species: Metriochroa alboannulata Bai, sp. n. and Gibbovalva clavata Bai, sp. n. Eumetriochroa hiranoi Kumata, 1998, is newly recorded from China. Photographs of adults and figures of the genital structures are provided, along with keys to the Chinese species of Metriochroa, Eumetriochroa, and Gibbovalva. PMID- 27006610 TI - On the synonymy of two Acantholycosa species (Araneae, Lycosidae) from the Altai. AB - Two species previously known from East Kazakhstan, Acantholycosa katunensis Marusik, Azarkina & Koponen, 2004, known from the holotype male, and Acantholycosa kurchumensis Marusik, Azarkina & Koponen, 2004, syn. n. known from females, are synonymized, and priority is given to Acantholycosa katunensis. Acantholycosa katunensis is reported for the first time in the Russian Altai. Both sexes of this species are illustrated, and a distribution map is provided. PMID- 27006612 TI - Six new species of the spider genus Spiricoelotes species (Araneae, Agelenidae) from caves in Jiangxi, China. AB - Six new species of the spider genus Spiricoelotes Wang, 2002 are described, Spiricoelotes anshiensis Chen & Li, sp. n. (??), Spiricoelotes chufengensis Chen & Li, sp. n. (??), Spiricoelotes nansheensis Chen & Li, sp. n. (??), Spiricoelotes taipingensis Chen & Li, sp. n. (??), Spiricoelotes xianheensis Chen & Li, sp. n. (??) and Spiricoelotes xiongxinensis Chen & Li, sp. n. (?). All new species were collected from caves in Jiangxi Province, China. PMID- 27006611 TI - Taxonomic revision of the tarantula genus Aphonopelma Pocock, 1901 (Araneae, Mygalomorphae, Theraphosidae) within the United States. AB - This systematic study documents the taxonomy, diversity, and distribution of the tarantula spider genus Aphonopelma Pocock, 1901 within the United States. By employing phylogenomic, morphological, and geospatial data, we evaluated all 55 nominal species in the United States to examine the evolutionary history of Aphonopelma and the group's taxonomy by implementing an integrative approach to species delimitation. Based on our analyses, we now recognize only 29 distinct species in the United States. We propose 33 new synonymies (Aphonopelma apacheum, Aphonopelma minchi, Aphonopelma rothi, Aphonopelma schmidti, Aphonopelma stahnkei = Aphonopelma chalcodes; Aphonopelma arnoldi = Aphonopelma armada; Aphonopelma behlei, Aphonopelma vogelae = Aphonopelma marxi; Aphonopelma breenei = Aphonopelma anax; Aphonopelma chambersi, Aphonopelma clarum, Aphonopelma cryptethum, Aphonopelma sandersoni, Aphonopelma sullivani = Aphonopelma eutylenum; Aphonopelma clarki, Aphonopelma coloradanum, Aphonopelma echinum, Aphonopelma gurleyi, Aphonopelma harlingenum, Aphonopelma odelli, Aphonopelma waconum, Aphonopelma wichitanum = Aphonopelma hentzi; Aphonopelma heterops = Aphonopelma moderatum; Aphonopelma jungi, Aphonopelma punzoi = Aphonopelma vorhiesi; Aphonopelma brunnius, Aphonopelma chamberlini, Aphonopelma iviei, Aphonopelma lithodomum, Aphonopelma smithi, Aphonopelma zionis = Aphonopelma iodius; Aphonopelma phanum, Aphonopelma reversum = Aphonopelma steindachneri), 14 new species (Aphonopelma atomicum sp. n., Aphonopelma catalina sp. n., Aphonopelma chiricahua sp. n., Aphonopelma icenoglei sp. n., Aphonopelma johnnycashi sp. n., Aphonopelma madera sp. n., Aphonopelma mareki sp. n., Aphonopelma moellendorfi sp. n., Aphonopelma parvum sp. n., Aphonopelma peloncillo sp. n., Aphonopelma prenticei sp. n., Aphonopelma saguaro sp. n., Aphonopelma superstitionense sp. n., and Aphonopelma xwalxwal sp. n.), and seven nomina dubia (Aphonopelma baergi, Aphonopelma cratium, Aphonopelma hollyi, Aphonopelma mordax, Aphonopelma radinum, Aphonopelma rusticum, Aphonopelma texense). Our proposed species tree based on Anchored Enrichment data delimits five major lineages: a monotypic group confined to California, a western group, an eastern group, a group primarily distributed in high-elevation areas, and a group that comprises several miniaturized species. Multiple species are distributed throughout two biodiversity hotspots in the United States (i.e., California Floristic Province and Madrean Pine-Oak Woodlands). Keys are provided for identification of both males and females. By conducting the most comprehensive sampling of a single theraphosid genus to date, this research significantly broadens the scope of prior molecular and morphological investigations, finally bringing a modern understanding of species delimitation in this dynamic and charismatic group of spiders. PMID- 27006613 TI - A new sharpshooter genus for Sphinctogonia lingula Yang & Li (Hemiptera, Cicadellidae, Cicadellini) from China. AB - A new genus, Sphinctogoniella, is described to accommodate Sphinctogonia lingula Yang & Li, 2002, its type species from China. Sphinctogoniella lingula (Yang & Li, 2002), comb. n. is re-described and illustrated. Differences between the new genus and Sphinctogonia Breddin, 1901 are tabulated. PMID- 27006614 TI - A new species of the genus Anteon Jurine (Hymenoptera, Dryinidae) from Laos. AB - A new species of Anteon Jurine, 1807 is described from Laos, Houaphanh Province: Anteon holzschuhi sp. n. Morphologically the new species is similar to Anteon semipolitum Olmi, 2008, but it is distinguished by the sculpture of the face partly reticulate rugose and partly with deep punctures similar to areolae; in Anteon semipolitum the face is completely punctate and unsculptured among punctures. In addition, in the new species the distance from the outer edge of a lateral ocellus to the compound eye (OOL) is about 3.3 times as long as the distance between the inner edges of a lateral ocellus and the median ocellus (OL); in Anteon semipolitum OOL is less than twice as long as OL. Published identification keys to the Oriental species of Anteon are modified to include the new species. PMID- 27006615 TI - Description of the female of Haematonotus jenisi Krajcik, 2006 and placement of the species within the genus Atrichiana Distant, 1911 (Coleoptera, Scarabaeidae, Cetoniinae). AB - The male of Haematonotus jenisi Krajcik, 2006 was described on the basis of a sole holotype specimen. A number of new specimens have recently been collected from the False Bay area of the iSimangaliso Wetland Park, in northeastern KwaZulu Natal, including a number of females, thereby allowing the description of this sex for the first time. The new series also reveals that most morphological characters are actually typical for the genus Atrichiana Distant, 1911, rather than Haematonotus Kraatz, 1880. For this reason, it is here proposed that this species be placed within Atrichiana, thus becoming the second species of a genus that was previously regarded as monospecific, represented by the southern African endemic Atrichiana placida (Boheman, 1857). Like Atrichiana placida, Atrichiana jenisi exhibits a remarkable polymorphism, but also sexual dimorphism, particularly expressed at the level of the antennal clubs, which in the male are twice as long as in the female. Unfortunately, all specimens of the recent series were collected dead or drowning on the lake shores and therefore no further information on their life cycle and biology in general could be obtained. It seems that the species may represent a micro-endemism restricted to the Western Shores of Lake St Lucia, with habitat associated to Sand Forest and possibly also Northern Coastal Forest vegetation types. PMID- 27006616 TI - Morphology of juvenile stages of Kuschelina bergi (Harold) with biological information (Coleoptera, Chrysomelidae, Alticini). AB - Kuschelina bergi (Harold, 1881) is being studied to be evaluated as a natural enemy of Phyla nodiflora var. minor (Hook.) N. O'Leary & Mulgura (Verbenaceae), an invasive weed in Australia. Eggs, and 1(st) and 3(rd) instar larvae are described and illustrated for the first time. The following characters distinguish Kuschelina bergi: presence of two medial setae in prosternum, mesosternum and metasternum, absence of tubercle on sternum I and eight setae in abdominal segment IX. The 3(rd) instar larvae of Kuschelina bergi resemble Kuschelina gibbitarsa (Say) larvae: the body shape and details of mouthparts are similar, but the morphology of the mandible is different, as is the tarsungulus which has a single seta. Differences between Kuschelina bergi and other known larvae of Oedionychina are discussed. New biological data based on laboratory rearing and field observation are also presented and discussed. PMID- 27006617 TI - Salt lakes of La Mancha (Central Spain): A hot spot for tiger beetle (Carabidae, Cicindelinae) species diversity. AB - The tiger beetle assemblage of the wetlands of La Mancha (central Spain) comprises nine species: Calomera littoralis littoralis, Cephalota maura maura, Cephalota circumdata imperialis, Cephalota dulcinea, Cicindela campestris campestris, Cicindela maroccana, Cylindera paludosa, Lophyra flexuosa flexuosa, and Myriochila melancholica melancholica. This assemblage represents the largest concentration of tiger beetles in a single 1o latitude / longitude square in Europe. General patterns of spatial and temporal segregation among species are discussed based on observations of 1462 specimens registered during an observation period of one year, from April to August. The different species of Cicindelini appear to be distributed over space and time, with little overlapping among them. Three sets of species replace each other phenologically as the season goes on. Most of the species occupy drying or dried salt lakes and salt marshes, with sparse vegetation cover. Spatial segregation is marked in terms of substrate and vegetation use. Calomera littoralis and Myriochila melancholica have been observed mainly on wet soils; Cephalota circumdata on dry open saline flats; Cephalota dulcinea and Cylindera paludosa in granulated substrates with typical halophytic vegetation; Cephalota maura is often present in man-modified areas. Cephalota circumdata and Cephalota dulcinea are included as species of special interest in the list of protected species in Castilla-La Mancha. Conservation problems for the Cicindelini assemblage arise from agricultural activities and inadequate use of sport vehicles. Attempts at restoring the original habitat, supressing old semi-industrial structures, may affect the spatial heterogeneity of the lakes, and have an effect on Cicindelinae diversity. PMID- 27006618 TI - Pempheris gasparinii, a new species of sweeper fish from Trindade Island, southwestern Atlantic (Teleostei, Pempheridae). AB - Pempheris gasparinii sp. n. is described from five specimens, 59.1-68.0 mm in standard length. It is only known to occur in the shallow reefs of Trindade Island, 1200 km east of the Brazilian coast, in the southwestern Atlantic. Pempheris gasparinii is the third recognized species of Pempheris in the Atlantic Ocean. This new species is morphologically similar to its close relative, Pempheris poeyi, differing by the number of lateral-line scales (51-54 in Pempheris gasparinii vs. 47-49 in Pempheris poeyi), scales below lateral line (10 11 vs. 9), circumpeduncular scales (11-12 vs. 13), head and caudal peduncle lengths (2.7-3.3 vs 3.5-4.0 in head length). Moreover, Pempheris gasparinii shows a 4% genetic divergence from Pempheris poeyi at the cytochrome oxidase I locus (COI), consistent with a lineage split at the beginning of the Pleistocene. This new species represents the 12(th) endemic fish species from Trindade Island. PMID- 27006619 TI - Cryptomyrus: a new genus of Mormyridae (Teleostei, Osteoglossomorpha) with two new species from Gabon, West-Central Africa. AB - We use mitochondrial and nuclear sequence data to show that three weakly electric mormyrid fish specimens collected at three widely separated localities in Gabon, Africa over a 13-year period represent an unrecognized lineage within the subfamily Mormyrinae and determine its phylogenetic position with respect to other taxa. We describe these three specimens as a new genus containing two new species. Cryptomyrus, new genus, is readily distinguished from all other mormyrid genera by a combination of features of squamation, morphometrics, and dental attributes. Cryptomyrus ogoouensis, new species, is differentiated from its single congener, Cryptomyrus ona, new species, by the possession of an anal-fin origin located well in advance of the dorsal fin, a narrow caudal peduncle and caudal-fin lobes nearly as long as the peduncle. In Cryptomyrus ona, the anal-fin origin is located only slightly in advance of the dorsal fin, the caudal peduncle is deep and the caudal-fin lobes considerably shorter than the peduncle. Continued discovery of new taxa within the "Lower Guinea Clade" of Mormyridae highlights the incompleteness of our knowledge of fish diversity in West-Central Africa. We present a revised key to the mormyrid genera of Lower Guinea. PMID- 27006620 TI - A key to the genera and species of the transversely-dividing Flabellidae (Anthozoa, Scleractinia, Flabellidae), with a guide to the literature, and the description of two new species. AB - The transversely-dividing flabellids consist of five genera (Truncatoflabellum, Placotrochides, Blastotrochus, Placotrochus, and Falcatoflabellum) and 45 species. A dichotomous key is provided for these five genera as well as the species of the genus Truncatoflabellum and Placotrochides, the other three genera being monotypic. A tabular key is also provided for the 38 species of Truncatoflabellum. Two new combinations are suggested (Truncatoflabellum gambierense and Truncatoflabellum sphenodeum) and two new species are described (Truncatoflabellum duncani and Truncatoflabellum mozambiquensis). All but one species are illustrated and accompanied by their known distribution and a guide to the pertinent literature for the species. New records of 19 of the 45 species are listed. The transversely-dividing flabellids range from the Middle Eocene to the Recent at depths of 2-3010 m, and constitute 60% of the 65 known extant species of transversely-dividing Scleractinia. PMID- 27006621 TI - Unexpected diversity and a new species of Epizoanthus (Anthozoa, Hexacorallia) attached to eunicid worm tubes from the Pacific Ocean. AB - Epizoanthus species are generally found in association with other marine invertebrates such as hermit crabs and gastropods. Although Epizoanthus spp. are relatively common, there is limited information about their diversity and ecology due to their habitats or hosts, often being below the depths of SCUBA diving (>~50 m). In particular, the Epizoanthus fauna of the Indo-Pacific Ocean remains poorly understood. In this study, the diversity of Epizoanthus species associated with eunicid worm tubes from shallow waters in the Pacific Ocean we investigated using molecular analyses (mitochondrial cytochrome oxidase subunit 1 = COI, mitochondrial 16S ribosomal DNA = mt 16S-rDNA, nuclear internal transcribed spacer region of ribosomal DNA = ITS-rDNA) combined with morphological and ecological data. The combined data set leads us to describe two new species; Epizoanthus inazuma sp. n. and Epizoanthus beriber sp. n. Both new species are found in low-light environments: Epizoanthus inazuma sp. n. on mesophotic coral reef slopes and reef floors, or on the sides of overhangs; Epizoanthus beriber sp. n. has only been found in caves. Morphological characteristics of these two new species are very similar to Epizoanthus illoricatus Tischbierek, 1930 but the two new species are genetically distinct. Mesentery numbers and coloration of polyps may be useful diagnostic characteristics among eunicid-associated Epizoanthus species. These results demonstrate that there is high potential for other potentially undescribed zoantharian species, particularly in underwater cave habitats. PMID- 27006622 TI - Review of the South American leafhopper genus Parandanus (Hemiptera, Cicadellidae, Deltocephalinae). AB - The South American leafhopper genus Parandanus Linnavuori & DeLong (Deltocephalinae: Deltocephalini) is reviewed and four of its six species are illustrated and male genital characters are provided. Three new species from Peru, Parandanus longistylus Duan, sp. n., Parandanus nigricephalus Duan, sp. n. and Parandanus paracruciatus Duan, sp. n. are described. A key to species is also provided. PMID- 27006623 TI - A review of the genera Gnathochorisis Forster and Symplecis Forster of South Korea, with notes on Korean orthocentrines (Hymenoptera, Ichneumonidae, Orthocentrinae). AB - Two genera of Korean Orthocentrinae, Gnathochorisis and Symplecis, are reviewed, and keys to species of these genera are provided here. Two new species, Gnathochorisis fuscipes Humala & Lee, sp. n. and Gnathochorisis koreensis Humala & Lee, sp. n. are described from South Korea. The current state of the taxonomy of Eastern Palaearctic orthocentrines is briefly discussed. PMID- 27006624 TI - The Knight and the King: two new species of giant bent-toed gecko (Cyrtodactylus, Gekkonidae, Squamata) from northern New Guinea, with comments on endemism in the North Papuan Mountains. AB - The diverse biota of New Guinea includes many nominally widespread species that actually comprise multiple deeply divergent lineages with more localised histories of evolution. Here we investigate the systematics of the very large geckos of the Cyrtodactylus novaeguineae complex using molecular and morphological data. These data reveal two widespread and divergent lineages that can be distinguished from each other, and from type material of Cyrtodactylus novaeguineae, by aspects of size, build, coloration and male scalation. On the basis of these differences we describe two new species. Both have wide distributions that overlap extensively in the foothill forests of the North Papuan Mountains, however one is seemingly restricted to hill and lower montane forests on the ranges themselves, while the other is more widespread throughout the surrounding lowlands. The taxon endemic to the North Papuan Mountains is related to an apparently lowland form currently known only from Waigeo and Batanta Island far to the west - hinting at a history on island arcs that accreted to form the North Papuan Mountains. PMID- 27006625 TI - The desert tortoise trichotomy: Mexico hosts a third, new sister-species of tortoise in the Gopherus morafkai-G. agassizii group. AB - Desert tortoises (Testudines; Testudinidae; Gopherus agassizii group) have an extensive distribution throughout the Mojave, Colorado, and Sonoran desert regions. Not surprisingly, they exhibit a tremendous amount of ecological, behavioral, morphological and genetic variation. Gopherus agassizii was considered a single species for almost 150 years but recently the species was split into the nominate form and Morafka's desert tortoise, Gopherus morafkai, the latter occurring south and east of the Colorado River. Whereas a large body of literature focuses on tortoises in the United States, a dearth of investigations exists for Mexican animals. Notwithstanding, Mexican populations of desert tortoises in the southern part of the range of Gopherus morafkai are distinct, particularly where the tortoises occur in tropical thornscrub and tropical deciduous forest. Recent studies have shed light on the ecology, morphology and genetics of these southern 'desert' tortoises. All evidence warrants recognition of this clade as a distinctive taxon and herein we describe it as Gopherus evgoodei sp. n. The description of the new species significantly reduces and limits the distribution of Gopherus morafkai to desertscrub habitat only. By contrast, Gopherus evgoodei sp. n. occurs in thornscrub and tropical deciduous forests only and this leaves it with the smallest range of the three sister species. We present conservation implications for the newly described Gopherus evgoodei, which already faces impending threats. PMID- 27006626 TI - Analysis of PRKN Variants and Clinical Features in Polish Patients with Parkinson's Disease. AB - The etiology of Parkinson's disease (PD) is still unclear, but mutations in PRKN have provided some biological insights. The role of PRKN mutations and other genetic variation in determining the clinical features of PD remains unresolved. The aim of the study was to analyze PRKN mutations in PD and controls in the Polish population and to try to correlate between the presence of genetic variants and clinical features. We screened for PRKN mutations in 90 PD patients and 113 controls and evaluated clinical features in these patients. We showed that in the Polish population 4% of PD patients had PRKN mutations (single or with additional polymorphism) while single heterozygous polymorphisms (S167N, E310D, D394N) of PRKN were present in 21% of sporadic PD. Moreover, 5% PD patients had more than one PRKN change (polymorphisms and mutations). Detected PRKN variants moderately correlated with PD course and response to L-dopa. It also showed that other PARK genes (SNCA, HTRA2, SPR) mutations probably may additionally influence PD risk and clinical features. PRKN variants are relatively common in our Polish series of patients with PD. Analysis of the PRKN gene may be useful in determining clinical phenotype, and helping with diagnostic and prognostic procedures in the future. PMID- 27006627 TI - It's Time for An Epigenomics Roadmap of Heart Failure. AB - The post-genomic era has completed its first decade. During this time, we have seen an attempt to understand life not just through the study of individual isolated processes, but through the appreciation of the amalgam of complex networks, within which each process can influence others. Greatly benefiting this view has been the study of the epigenome, the set of DNA and histone protein modifications that regulate gene expression and the function of regulatory non coding RNAs without altering the DNA sequence itself. Indeed, the availability of reference genome assemblies of many species has led to the development of methodologies such as ChIP-Seq and RNA-Seq that have allowed us to define with high resolution the genomic distribution of several epigenetic elements and to better comprehend how they are interconnected for the regulation of gene expression. In the last few years, the use of these methodologies in the cardiovascular field has contributed to our understanding of the importance of epigenetics in heart diseases, giving new input to this area of research. Here, we review recently acquired knowledge on the role of the epigenome in heart failure, and discuss the need of an epigenomics roadmap for cardiovascular disease. PMID- 27006629 TI - Clinical Next Generation Sequencing for Precision Medicine in Cancer. AB - Rapid adoption of next generation sequencing (NGS) in genomic medicine has been driven by low cost, high throughput sequencing and rapid advances in our understanding of the genetic bases of human diseases. Today, the NGS method has dominated sequencing space in genomic research, and quickly entered clinical practice. Because unique features of NGS perfectly meet the clinical reality (need to do more with less), the NGS technology is becoming a driving force to realize the dream of precision medicine. This article describes the strengths of NGS, NGS panels used in precision medicine, current applications of NGS in cytology, and its challenges and future directions for routine clinical use. PMID- 27006628 TI - Inside the Pan-genome - Methods and Software Overview. AB - The number of genomes that have been deposited in databases has increased exponentially after the advent of Next-Generation Sequencing (NGS), which produces high-throughput sequence data; this circumstance has demanded the development of new bioinformatics software and the creation of new areas, such as comparative genomics. In comparative genomics, the genetic content of an organism is compared against other organisms, which helps in the prediction of gene function and coding region sequences, identification of evolutionary events and determination of phylogenetic relationships. However, expanding comparative genomics to a large number of related bacteria, we can infer their lifestyles, gene repertoires and minimal genome size. In this context, a powerful approach called Pan-genome has been initiated and developed. This approach involves the genomic comparison of different strains of the same species, or even genus. Its main goal is to establish the total number of non-redundant genes that are present in a determined dataset. Pan-genome consists of three parts: core genome; accessory or dispensable genome; and species-specific or strain-specific genes. Furthermore, pan-genome is considered to be "open" as long as new genes are added significantly to the total repertoire for each new additional genome and "closed" when the newly added genomes cannot be inferred to significantly increase the total repertoire of the genes. To perform all of the required calculations, a substantial amount of software has been developed, based on orthologous and paralogous gene identification. PMID- 27006631 TI - Another Important News from the Neuronman: Malaysia's Neuroscience Group Moves upwards in Terms of Research, Creativity, and Innovation. AB - 12 months ago the first Neuroscience special issue of the Malaysia Journal of Medical Sciences was born with the intention to increase the number of local publication dedicated to neurosciences. Since then many events happened in the neuroscience world of Malaysia, those considered major were the establishment of a Neurotechnology Foresight 2050 task force by the Academy of Medicine Malaysia as well as the launching of Malaysia as the 18th member to join the International Neuroinformatics Coordinating Facility on the 9th October 2015 which was officiated by the Deputy Ministers of Higher Education, Datuk Mary Yap. PMID- 27006630 TI - Genome-wide Scanning and Characterization of Sorghum bicolor L. Heat Shock Transcription Factors. AB - A genome-wide scanning of Sorghum bicolor resulted in the identification of 25 SbHsf genes. Phylogenetic analysis shows the ortholog genes that are clustered with only rice, representing a common ancestor. Promoter analysis revealed the identification of different cis-acting elements that are responsible for abiotic as well as biotic stresses. Hsf domains like DBD, NLS, NES, and AHA have been analyzed for their sequence similarity and functional characterization. Tissue specific expression patterns of Hsfs in different tissues like mature embryo, seedling, root, and panicle were studied using real-time PCR. While Hsfs4 and 22 are highly expressed in panicle, 4 and 9 are expressed in seedlings. Sorghum plants were exposed to different abiotic stress treatments but no expression of any Hsf was observed when seedlings were treated with ABA. High level expression of Hsf1 was noticed during high temperature as well as cold stresses, 4 and 6 during salt and 5, 6, 10, 13, 19, 23 and 25 during drought stress. This comprehensive analysis of SbHsf genes will provide an insight on how these genes are regulated in different tissues and also under different abiotic stresses and help to determine the functions of Hsfs during drought and temperature stress tolerance. PMID- 27006632 TI - History of Neurosurgery in Malaysia. AB - The development of neurosurgical services and training in Malaysia began in 1963, with the first centre established in its capital city at Hospital Kuala Lumpur, aimed to provide much needed neurosurgical services and training in the field of neurology and neurosurgery. This center subsequently expanded in 1975 with the establishment of the Tunku Abdul Rahman Neuroscience Institute (IKTAR); which integrated the three allied interdependent disciplines of neurosurgery, neurology and psychiatry. The establishment of this institute catalysed the rapid expansion of neurosurgical services in Malaysia and paved the way for development of comprehensive training for doctors, nurses, and paramedics. This culminated in the establishments of a local comprehensive neurosurgery training program for doctors in 2001; followed by a training program for nurses and paramedics in 2006. To date, there are more than 60 neurosurgeons providing expert care in 11 centers across Malaysia, along with trained personnel in the field of neurosciences. PMID- 27006633 TI - A Review on the Bioinformatics Tools for Neuroimaging. AB - Neuroimaging is a new technique used to create images of the structure and function of the nervous system in the human brain. Currently, it is crucial in scientific fields. Neuroimaging data are becoming of more interest among the circle of neuroimaging experts. Therefore, it is necessary to develop a large amount of neuroimaging tools. This paper gives an overview of the tools that have been used to image the structure and function of the nervous system. This information can help developers, experts, and users gain insight and a better understanding of the neuroimaging tools available, enabling better decision making in choosing tools of particular research interest. Sources, links, and descriptions of the application of each tool are provided in this paper as well. Lastly, this paper presents the language implemented, system requirements, strengths, and weaknesses of the tools that have been widely used to image the structure and function of the nervous system. PMID- 27006634 TI - Magnetoencephalography Phantom Comparison and Validation: Hospital Universiti Sains Malaysia (HUSM) Requisite. AB - BACKGROUND: Magnetoencephalography (MEG) has been extensively used to measure small-scale neuronal brain activity. Although it is widely acknowledged as a sensitive tool for deciphering brain activity and source localisation, the accuracy of the MEG system must be critically evaluated. Typically, on-site calibration with the provided phantom (Local phantom) is used. However, this method is still questionable due to the uncertainty that may originate from the phantom itself. Ideally, the validation of MEG data measurements would require cross-site comparability. METHOD: A simple method of phantom testing was used twice in addition to a measurement taken with a calibrated reference phantom (RefPhantom) obtained from Elekta Oy of Helsinki, Finland. The comparisons of two main aspects were made in terms of the dipole moment (Qpp) and the difference in the dipole distance from the origin (d) after the tests of statistically equal means and variance were confirmed. RESULT: The result of Qpp measurements for the LocalPhantom and RefPhantom were 978 (SD24) nAm and 988 (SD32) nAm, respectively, and were still optimally within the accepted range of 900 to 1100 nAm. Moreover, the shifted d results for the LocalPhantom and RefPhantom were 1.84 mm (SD 0.53) and 2.14 mm (SD 0.78), respectively, and these values were below the maximum acceptance range of within 5.0 mm of the nominal dipole location. CONCLUSION: The Local phantom seems to outperform the reference phantom as indicated by the small standard error of the former (SE 0.094) compared with the latter (SE 0.138). The result indicated that HUSM MEG system was in excellent working condition in terms of the dipole magnitude and localisation measurements as these values passed the acceptance limits criteria of the phantom test. PMID- 27006635 TI - Cognitive Profiles in Parkinson's Disease and their Correlation with Dementia, Anxiety and Depression: A Preliminary Study. AB - A cross-sectional study was carried out at a medical centre to determine the cognitive profiles of 30 Parkinson's disease patients with age of 69.76 +/- 7.39 years. Thirty-seven percent of the patients were found to be at risk for dementia. The scores on subscales of working memory and alternating verbal fluency were significantly lower in Parkinson's disease patients who were older than 77 years old. The scores on a subtest of working memory on the Parkinson's Disease Cognitive Rating Scale (PDCRS) were significantly lower in Parkinson's disease patients with a duration of illness of more than 10 years. In cognitive measurement, the subtests of verbal memory, delayed free recall and verbal fluency on the PD!CRS were significantly lower in patients with less than six years of education. The patients who had difficulty with sustained attention, working memory and movement had significant anxiety and depression symptoms. In conclusion, multiple patterns in cognitive profiles influence the quality of life of patients with Parkinson's disease in multi-dimensional ways. PMID- 27006636 TI - Theta-burst Transcranial Magnetic Stimulation Alters the Functional Topography of the Cortical Motor Network. AB - BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive tool that is able to modulate the electrical activity of the brain depending upon its protocol of stimulation. Theta burst stimulation (TBS) is a high-frequency TMS protocol that is able to induce prolonged plasticity changes in the brain. The induction of plasticity-like effects by TBS is useful in both experimental and therapeutic settings; however, the underlying neural mechanisms of this modulation remain unclear. The aim of this study was to investigate the effects of continuous TBS (cTBS) on the intrahemispheric and interhemispheric functional connectivity of the resting and active brain. METHODS: A total of 26 healthy humans were randomly divided into two groups that received either real cTBS or sham (control) over the left primary motor cortex. Surface electroencephalogram (EEG) was used to quantify the changes of neural oscillations after cTBS at rest and after a choice reaction time test. The cTBS-induced EEG oscillations were computed using spectral analysis of event-related coherence (ERCoh) of theta (4 7.5 Hz), low alpha (8-9.5 Hz), high alpha (10-12.5 Hz), low beta (13-19.5 Hz), and high beta (20-30 Hz) brain rhythms. RESULTS: We observed a global decrease in functional connectivity of the brain in the cTBS group when compared to sham in the low beta brain rhythm at rest and high beta brain rhythm during the active state. In particular, EEG spectral analysis revealed that high-frequency beta, a cortically generated brain rhythm, was the most sensitive band that was modulated by cTBS. CONCLUSION: Overall, our findings suggest that cTBS, a TMS protocol that mimics the mechanism of long-term depression of synaptic plasticity, modulates motor network oscillations primarily at the cortical level and might interfere with cortical information coding. PMID- 27006637 TI - Behavioural and Electrophysiological Evidence of Impaired Learning and Memory in Male Sprague Dawley Rats following Subchronic Exposure to Standardised Methanolic Extract of Mitragyna speciosa Korth. AB - BACKGROUND: Mitragyna speciosa (MS) or ketum is primarily found in Southeast Asia, particularly in northern Malaysia and Thailand. The medicinal value of this plant has attracted significant attention from both herbal medicine practitioners and scientists worldwide. Despite having illegal consumption status, the plant merits study. We conducted a series of experiments to test our hypothesis that ketum impairs both learning and memory in rats. METHODS: Ketum leaves were extracted using methanol and standardised for the amount of its pure compound, mitragynine. Rats were divided into groups for a passive avoidance task and long term potentiation (LTP) extracellular recording. In the extracellular recording condition, rats were grouped into control, MS100 (100 mg/kg of ketum extract), MS200 (200 mg/kg of ketum extract), and MS500 (500 mg/kg of ketum extract) groups. An additional group that received morphine was included in the passive avoidance task (10 mg/kg), and there were six animals per group. Rats received daily treatments orally for 28 days for both experiments. RESULT: Using a passive avoidance task, our data revealed that the rats' memory significantly increased with increasing doses of MS compared to the morphine-treated group. Our findings from LTP recordings showed that LTP was fully blocked by the higher doses of MS. CONCLUSION: We speculate on the possibility that additional factors were involved in the passive avoidance task because it was an in vivo animal study, while the LTP experiment solely involved brain slices. PMID- 27006638 TI - Pain in Times of Stress. AB - Stress modulates pain perception, resulting in either stress-induced analgesia or stress-induced hyperalgesia, as reported in both animal and human studies. The responses to stress include neural, endocrine, and behavioural changes, and built in coping strategies are in place to address stressors. Peculiar to humans are additional factors that modulate pain that are experienced in times of stress, notably psychological factors that potentially influence the directionality of pain perception. PMID- 27006639 TI - Tranexamic Acid as Antifibrinolytic Agent in Non Traumatic Intracerebral Hemorrhages. AB - BACKGROUND: Mortality and morbidity associated with intracerebral hemorrhage is still high. Up to now, there are no evidence-based effective treatments for acute ICH. This study is to assess the effect of tranexamic acid (TXA) on hematoma growth of patients with spontaneous ICH compared to a placebo. METHODS: We performed a single-blinded, randomised placebo-controlled trial of TXA (intravenous 1g bolus, followed by infusion TXA 1 g/hour for 8 hours) in acute (< 8 hours) primary ICH. Strict blood pressure control (target SBP 140-160 mmHg). A repeat Computed Tomography brain was done after 24 hours to reassess hematoma growth. The primary objective is to test the effect of TXA on hematoma growth. Other objective was to test the feasibility, tolerability, and adverse events of TXA in primary ICH. RESULTS: Statistical analysis showed significant hematoma growth in control group after 24 hours compared to baseline (14.3300 vs 17.9940, P = 0.001) whereas the treatment group there is no significant hematoma size expansion between baseline and after 24 hours (P = 0.313). CONCLUSIONS: This study showed a significant hematoma volume expansion in the control group compared to the treatment group. PMID- 27006641 TI - Concurrent validity of self-rating scale of self-directed learning and self directed learning instrument among Italian nursing students. AB - BACKGROUND: Self-Directed Learning develops when students take the initiative for their learning, recognising needs, formulating goals, identifying resources, implementing appropriate strategies and evaluating learning outcomes. This should be seen as a collaborative process between the nurse educator and the learner. At the international level, various instruments have been used to measure Self Directed Learning abilities (SDL), both in original and in culturally-adapted versions. However, few instruments have been subjected to full validation, and no gold standard reference has been established to date. In addition, few researchers have adopted the established tools to assess the concurrent validity of the emerging new tools. Therefore, the aim of this study was to measure the concurrent validity between the Self-Rating Scale of Self-Directed Learning (SRSSDL_Ita) - Italian version and the Self-Directed Learning Instruments (SDLI) in undergraduate nursing students. METHODS: A concurrent validity study design was conducted in a Bachelor level nursing degree programme located in Italy. All nursing students attending the first, second or third year (n = 428) were the target sample. The SRSSDL_Ita, and the SDLI were used. The Pearson correlation was used to determine the concurrent validity between the instruments; the confidence of intervals (CI 95 %) bias-corrected and accelerated bootstrap (BCa), were also calculated. RESULTS: The majority of participants were students attending their first year (47.9 %), and were predominately female (78.5 %). Their average age was 22.5 +/- 4.1. The SDL abilities scores, as measured with the SRSSDL_Ita (min 40, max 200), were, on average, 160.79 (95 % CI 159.10 162.57; median 160); while with the SDLI (min 20, max 100), they were on average 82.57 (95 % CI 81.79-83.38; median 83). The Pearson correlation between the SRSSDL_Ita and SDLI instruments was 0.815 (CI BCa 95 % 0.774-0.848), (p = 0.000). CONCLUSIONS: The findings confirm the concurrent validity of the SRSSDL_Ita with the SDLI. The SRSSDL_Ita instrument can be useful in the process of identifying Self-Directed Learning abilities, which are essential for students to achieve the expected learning goals and become lifelong learners. PMID- 27006642 TI - MiR-519d facilitates the progression and metastasis of cervical cancer through direct targeting Smad7. AB - BACKGROUND: MicroRNAs (miRNAs) play pivotal roles in the development of various cancer types, including cervical cancer. METHODS AND RESULTS: In this study, we showed that miR-519d, a miRNA within the chromosome 19 miRNA cluster, was significantly upregulated in cervical cancer tissues, compared with non-tumorous cervical samples. Suppression of miR-519d markedly attenuated the migration and invasion of HeLa and SiHa cervical cancer cells. Additionally, miR-519d inhibited the apoptosis of cervical cancer cells, and the proliferation of cervical cancer cells was also affected following transfection of miR-519d inhibitor. Moreover, we identified Smad7 to be a novel target of miR-519d in cervical cancer cells. MiR-519d matched the 3'-UTR of Smad7 mRNA. Transfection with miR-519d mimics led to apparent downregulation of Smad7 both at the mRNA and protein levels. Luciferase reporter analysis revealed that miR-519d reduced the luciferase activity of Smad7 mRNA 3'-UTR through matching site-dependent manner. And more notably, suppression of Smad7 remarkably restored the migration and invasion of miR-519d-depleted cervical cancer cells. CONCLUSION: Taken together, these findings implicated that miR-519d promoted the progression and metastasis of cervical cancer through targeting Smad7. PMID- 27006640 TI - Archaeal Community Changes Associated with Cultivation of Amazon Forest Soil with Oil Palm. AB - This study compared soil archaeal communities of the Amazon forest with that of an adjacent area under oil palm cultivation by 16S ribosomal RNA gene pyrosequencing. Species richness and diversity were greater in native forest soil than in the oil palm-cultivated area, and 130 OTUs (13.7%) were shared between these areas. Among the classified sequences, Thaumarchaeota were predominant in the native forest, whereas Euryarchaeota were predominant in the oil palm cultivated area. Archaeal species diversity was 1.7 times higher in the native forest soil, according to the Simpson diversity index, and the Chao1 index showed that richness was five times higher in the native forest soil. A phylogenetic tree of unclassified Thaumarchaeota sequences showed that most of the OTUs belong to Miscellaneous Crenarchaeotic Group. Several archaeal genera involved in nutrient cycling (e.g., methanogens and ammonia oxidizers) were identified in both areas, but significant differences were found in the relative abundances of Candidatus Nitrososphaera and unclassified Soil Crenarchaeotic Group (prevalent in the native forest) and Candidatus Nitrosotalea and unclassified Terrestrial Group (prevalent in the oil palm-cultivated area). More studies are needed to culture some of these Archaea in the laboratory so that their metabolism and physiology can be studied. PMID- 27006643 TI - The value of using a brain laser interstitial thermal therapy (LITT) system in patients presenting with high grade gliomas where maximal safe resection may not be feasible. AB - BACKGROUND: The objective of this analysis was to determine the value (incremental cost/increment benefit) of a brain LITT system versus employing current surgical options recommended by NCCN guidelines, specifically open resection (i.e. craniotomy) methods or biopsy (collectively termed CURRENT TREATMENTS) in patients where maximal safe resection may not be feasible. As has been demonstrated in the literature, extent of resection/ablation with minimal complications are independently related to overall survival. METHODS: A cost effectiveness analysis from a societal perspective was employed using TreeAge Pro 2014 software. Direct costs (using national average Medicare reimbursement amounts), outcomes (overall survival), and value [defined as increment cost/incremental survival-evaluated as cost/life year gained (LYG)] were evaluated. Sensitivity analysis was also performed to determine which variables had the largest effect on incremental costs and outcomes. RESULTS: In the base case, the overall survival was improved with brain LITT versus CURRENT TREATMENTS by 3.07 months at an additional cost of $7508 (or $29,340/LYG). This amount was significantly less than the current international threshold value for $32,575/LYG and considerably less than the US threshold value of $50,000/LYG. This incremental cost may also qualify under NICE criteria for end of life therapies. In sensitivity analysis: As percent local recurrence GBM increased; cost of DRG25/26 increased; percent GTR increased; and gliadel use increased-the value of brain LITT improved. Additionally, in those patients where a biopsy is the only option, brain LITT extended life by 7 months. CONCLUSIONS: Brain LITT should be considered a viable option for treatment of high grade gliomas as it improves survival at a cost which appears to be of good value to society. This incremental cost is less than the international and US thresholds for good value. PMID- 27006644 TI - Identifying potential differences in cause-of-death coding practices across Russian regions. AB - BACKGROUND: Reliable and comparable data on causes of death are crucial for public health analysis, but the usefulness of these data can be markedly diminished when the approach to coding is not standardized across territories and/or over time. Because the Russian system of producing information on causes of death is highly decentralized, there may be discrepancies in the coding practices employed across the country. In this study, we evaluate the uniformity of cause-of-death coding practices across Russian regions using an indirect method. METHODS: Based on 2002-2012 mortality data, we estimate the prevalence of the major causes of death (70 causes) in the mortality structures of 52 Russian regions. For each region-cause combination we measured the degree to which the share of a certain cause in the mortality structure of a certain region deviates from the respective inter-regional average share. We use heat map visualization and a regression model to determine whether there is regularity in the causes and the regions that is more likely to deviate from the average level across all regions. In addition to analyzing the comparability of cause-specific mortality structures in a spatial dimension, we examine the regional cause-of-death time series to identify the causes with temporal trends that vary greatly across regions. RESULTS: A high level of consistency was found both across regions and over time for transport accidents, most of the neoplasms, congenital malformations, and perinatal conditions. However, a high degree of inconsistency was found for mental and behavioral disorders, diseases of the nervous system, endocrine disorders, ill-defined causes of death, and certain cardiovascular diseases. This finding suggests that the coding practices for these causes of death are not uniform across regions. The level of consistency improves when causes of death can be grouped into broader diagnostic categories. CONCLUSION: This systematic analysis allows us to present a broader picture of the quality of cause-of-death coding at the regional level. For some causes of death, there is a high degree of variance across regions in the likelihood that these causes will be chosen as the underlying causes. In addition, for some causes of death the mortality statistics reflect the coding practices, rather than the real epidemiological situation. PMID- 27006645 TI - Multiple-bias analysis as a technique to address systematic error in measures of abortion-related mortality. AB - BACKGROUND: The UN Millennium Development Goals (MDGs) and Sustainable Development Goals (SDGs) have brought heightened global attention to the measurement of maternal mortality. It is imperative that new and novel approaches be used to measure maternal mortality and to better understand existing data. In this paper we present one approach: an epidemiologic framework for identifying the identification and quantification of systematic error (multiple-bias analysis), outline the necessary steps for investigators interested in conducting multiple-bias analyses in their own data, and suggest approaches for reporting such analyses in the literature. METHODS: To conceptualize the systematic error present in studies of abortion-related deaths, we propose a bias framework. We posit that selection bias and misclassification are present in both verbal autopsy studies and facility-based studies. The multiple-bias analysis framework provides a relatively simple, quantitative strategy for assessing systematic error and resulting bias in any epidemiologic study. RESULTS: In our worked example of multiple-bias analysis on a study reporting 20.6 % of maternal deaths to be abortion related, after adjustment for selection bias, misclassification, and random error, the median increased, on average, to 0.308, approximately 20 % greater than the reported proportion of abortion-related deaths. CONCLUSIONS: Reporting results of multiple-bias analyses in estimates of abortion-related mortality, predictors of unsafe abortion, and other reproductive health questions that suffer from similar biases would not only improve reporting practices in the field, but might also provide a more accurate understanding of the range of potential impact of policies and programs that target the underlying causes of unsafe abortion and abortion-related mortality. PMID- 27006646 TI - Next-Generation Sequencing-Based HPV Genotyping Assay Validated in Formalin Fixed, Paraffin-Embedded Oropharyngeal and Cervical Cancer Specimens. AB - Available clinical human papilloma virus (HPV) diagnostics for head and neck cancer have limited sensitivity and/or fail to define the HPV genotype. Common HPV genotyping assays are costly and labor intensive. We sought to develop a next generation sequencing (NGS)-based HPV genotyping assay that was sensitive enough to work on formalin-fixed paraffin-embedded (FFPE) samples. We developed an ion torrent NGS HPV genotyping assay using barcoded HPV PCR broad-spectrum general primers 5(+)/6(+) (BSGP)5(+)/6(+). To validate genotype specificity and use in archived clinical FFPE tumor samples, we compared NGS HPV genotyping at 2 sequencing centers with typing by Roche Linear Array assay in 42 oropharyngeal and cervical cancer specimens representing 10 HPV genotypes, as well as HPV negative cases. To demonstrate the detection of a broad range of HPV genotypes, we genotyped a cohort of 266 cervical cancers. A comparison of NGS genotyping of FFPE cancer specimens with genotyping by Linear Array showed concordant results in 34/37 samples (92%) at sequencing site 1 and 39/42 samples (93%) at sequencing site 2. Concordance between sites was 92%. Designed for use with 10 ng genomic DNA, the assay detected HPV using as little as 1.25 ng FFPE-derived genomic DNA. In 266 cervical cancer specimens, the NGS assay identified 20 different HPV genotypes, including all 13 carcinogenic genotypes. This novel NGS assay provides a sensitive and specific high-throughput method to detect and genotype HPV in a range of clinical specimens derived from FFPE with low per-sample cost. PMID- 27006647 TI - N-Terminal Amino Acid Sequence Determination of Proteins by N-Terminal Dimethyl Labeling: Pitfalls and Advantages When Compared with Edman Degradation Sequence Analysis. AB - In recent history, alternative approaches to Edman sequencing have been investigated, and to this end, the Association of Biomolecular Resource Facilities (ABRF) Protein Sequencing Research Group (PSRG) initiated studies in 2014 and 2015, looking into bottom-up and top-down N-terminal (Nt) dimethyl derivatization of standard quantities of intact proteins with the aim to determine Nt sequence information. We have expanded this initiative and used low picomole amounts of myoglobin to determine the efficiency of Nt-dimethylation. Application of this approach on protein domains, generated by limited proteolysis of overexpressed proteins, confirms that it is a universal labeling technique and is very sensitive when compared with Edman sequencing. Finally, we compared Edman sequencing and Nt-dimethylation of the same polypeptide fragments; results confirm that there is agreement in the identity of the Nt amino acid sequence between these 2 methods. PMID- 27006649 TI - Estimation of errors in diffraction data measured by CCD area detectors. AB - Current methods for diffraction-spot integration from CCD area detectors typically underestimate the errors in the measured intensities. In an attempt to understand fully and identify correctly the sources of all contributions to these errors, a simulation of a CCD-based area-detector module has been produced to address the problem of correct handling of data from such detectors. Using this simulation, it has been shown how, and by how much, measurement errors are underestimated. A model of the detector statistics is presented and an adapted summation integration routine that takes this into account is shown to result in more realistic error estimates. In addition, the effect of correlations between pixels on two-dimensional profile fitting is demonstrated and the problems surrounding improvements to profile-fitting algorithms are discussed. In practice, this requires knowledge of the expected correlation between pixels in the image. PMID- 27006650 TI - Prevalence of smoking and its associated factors with smoking among elderly smokers in Malaysia: findings from a nationwide population-based study. AB - BACKGROUND: The determination of smoking prevalence and its associated factors among the elderly could provide evidence-based findings to guide the planning and implementation of policy in order to will help in reducing the morbidity and mortality of smoking-related diseases, thus increase their quality of life. This paper describes the rate of smoking and identifies the factor(s) associated with smoking among the elderly in Malaysia. METHODS: A representative sample of 2674 respondents was obtained via a two-stage sampling method in proportion to population size. Face-to-face interviews were conducted using a set of standardized validated questionnaire. Data was weighted by taking into consideration the complex sampling design and non-response rate prior to data analysis. Univariable and multivariable logistic regression were used to determine the factor/s associated with smoking. RESULTS: The prevalence of non smokers, ex-smokers and current smokers among Malaysians aged 60 years and above were 36.3 % (95 % CI = 32.7-39.8), 24.4 % (95 % CI = 21.2-27.5) and 11.9 % (95 % CI = 9.5-14.3), respectively. Current smokers were significantly more prevalent in men (28.1 %) than in women (2.9 %), but the prevalence declined with advancing age, higher educational attainment, and among respondents with known diabetes, hypertension and hypercholesterolemia. Multivariable analysis revealed that males (aOR, 18.6, 95 % CI 10.9-31.9) and other Bumiputras (aOR 2.58, 95 % CI 1.29-5.15) were more likely to smoke. in addition, elderly with lower educational attainment (aOR, 1.70, 95 % CI 1.24-7.41) and those without/unknown hypertension also reported higher likelihood to be current smokers (aOR 1.98, 95 % CI 1.35-2.83). However, there were no significant associations between respondents with no/unknown diabetes or hypercholesterolemia with smoking. CONCLUSIONS: In short, smoking is common among elderly men in Malaysia. Therefore, intervention programs should integrate the present findings to reduce the smoking rate and increase the smoking cessation rate among the elderly in Malaysia and subsequently to reduce the burden of smoking-related disease. PMID- 27006651 TI - User Adaptive Text Predictor for Mentally Disabled Huntington's Patients. AB - This paper describes in detail the design of the specialized text predictor for patients with Huntington's disease. The main aim of the specialized text predictor is to improve the text input rate by limiting the phrases that the user can type in. We show that such specialized predictor can significantly improve text input rate compared to a standard general purpose text predictor. Specialized text predictor, however, makes it more difficult for the user to express his own ideas. We further improved the text predictor by using the sematic database to extract synonym, hypernym, and hyponym terms for the words that are not present in the training data of the specialized text predictor. This data can then be used to compute reasonable predictions for words that are originally not known to the text predictor. PMID- 27006652 TI - EEG Resting-State Brain Topological Reorganization as a Function of Age. AB - Resting state connectivity has been increasingly studied to investigate the effects of aging on the brain. A reduced organization in the communication between brain areas was demonstrated by combining a variety of different imaging technologies (fMRI, EEG, and MEG) and graph theory. In this paper, we propose a methodology to get new insights into resting state connectivity and its variations with age, by combining advanced techniques of effective connectivity estimation, graph theoretical approach, and classification by SVM method. We analyzed high density EEG signals recorded at rest from 71 healthy subjects (age: 20-63 years). Weighted and directed connectivity was computed by means of Partial Directed Coherence based on a General Linear Kalman filter approach. To keep the information collected by the estimator, weighted and directed graph indices were extracted from the resulting networks. A relation between brain network properties and age of the subject was found, indicating a tendency of the network to randomly organize increasing with age. This result is also confirmed dividing the whole population into two subgroups according to the age (young and middle aged adults): significant differences exist in terms of network organization measures. Classification of the subjects by means of such indices returns an accuracy greater than 80%. PMID- 27006653 TI - Cancer-Associated Immune Resistance and Evasion of Immune Surveillance in Colorectal Cancer. AB - Data from molecular profiles of tumors and tumor associated cells provide a model in which cancer cells can acquire the capability of avoiding immune surveillance by expressing an immune-like phenotype. Recent works reveal that expression of immune antigens (PDL1, CD47, CD73, CD14, CD68, MAC387, CD163, DAP12, and CD15) by tumor cells "immune resistance," combined with prometastatic function of nonmalignant infiltrating cells, may represent a strategy to overcome the rate limiting steps of metastatic cascade through (a) enhanced interactions with protumorigenic myeloid cells and escape from T-dependent immune response mediated by CD8+ and natural killer (NK) cells; (b) production of immune mediators that establish a local and systemic tumor-supportive environment (premetastatic niche); (c) ability to survive either in the peripheral blood as circulating tumor cells (CTCs) or at the metastatic site forming a cooperative prometastatic loop with foreign "myeloid" cells, macrophages, and neutrophils, respectively. The development of cancer-specific "immune resistance" can be orchestrated either by cooperation with tumor microenvironment or by successive rounds of genetic/epigenetic changes. Recognition of the applicability of this model may provide effective therapeutic avenues for complete elimination of immune resistant metastatic cells and for enhanced antitumor immunity as part of a combinatorial strategy. PMID- 27006655 TI - Vitamin D Supplementation and Hemoglobin Levels in Hypertensive Patients: A Randomized Controlled Trial. AB - Epidemiological evidence suggests that circulating 25-hydroxyvitamin D (25OHD) levels are inversely associated with hemoglobin (Hb) levels and anemia risk. We evaluated whether vitamin D supplementation improves Hb levels and reduces anemia risk in hypertensive patients. Two hundred patients with 25OHD levels <75 nmol/L who attended the Styrian Vitamin D Hypertension Trial were included, of whom 188 completed the trial. Patients randomly received 2800 IU vitamin D3 daily or a matching placebo for eight weeks. Initially, the prevalence of anemic status (Hb levels <12.5 g/dL) and deficient 25OHD levels (<30 nmol/L) was 6.5% and 7.5%, respectively. All anemic patients had 25OHD levels >50 nmol/L. The mean (95% confidence interval) vitamin D effect on Hb levels was 0.04 (-0.14 to 0.22) g/dL (P = 0.661). Moreover, vitamin D treatment did not influence anemic status significantly (P > 0.999). Likewise, vitamin D had no significant effect on Hb levels in the subgroups of anemic patients or in patients with initial 25OHD levels <30 nmol/L. In conclusion, a daily vitamin D supplement of 2800 IU for eight weeks did not improve Hb levels or anemic status in hypertensive patients. Future trials should focus on anemic patients with deficient 25OHD levels (e.g., <30 nmol/L). This trial is registered with clinicaltrials.gov [NCT02136771]. PMID- 27006656 TI - Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test. AB - Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 MUg) ACTH stimulation test at baseline and at 6-12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged >=18 years (HIV negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 MUg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug treatment and a negative mycobacterial culture (10.2 +/- 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat insufficient stimulated cortisol levels in the setting of MDR-TB. PMID- 27006657 TI - Pittsburgh as a High Risk Population: The Potential Savings of a Personalized Dental Care Plan. AB - Objectives. Little evidence exists for the current standard of two annual preventative care visits. The purpose of this study was investigate this claim by modeling the potential savings of implementing a personalized care plan for high risk individuals in the Pittsburgh region. Methods. Using radiographs from 39 patients in the University of Pittsburgh Dental Registry and DNA Repository database, two models were created to analyse the direct savings of implementing a more aggressive preventative treatment plan and to view the longitudinal cost of increased annual yearly visits. Results. There is a significant decrease (p < 0.001) between original and modeled treatment cost when treatment severity is reduced. In addition, there is a significant decrease in adult lifetime treatment cost (p < 0.001) for up to four annual visits. Conclusions. Patients in high risk populations may see significant cost benefits in treatment cost when a personalized care plan, or higher annual preventative care visits, is implemented. PMID- 27006658 TI - Biochemical Markers of Bone Turnover in Patients with beta-Thalassemia Major: A Single Center Study from Southern Pakistan. AB - Objectives. Skeletal complications in beta-homozygous thalassemic patients are uncommon but often debilitating, even amongst children and adolescent patients with well maintained transfusion and chelation therapy. The aim is to evaluate the biochemical markers of bone turnover in regularly transfused thalassemic patients and its possible correlations with demographic data and hematological and biochemical markers. Methods. In this prospective cross-sectional study, 36 beta-thalassemia major patients were enrolled from March 2012 to March 2014. All patients underwent complete blood counts, LFTs, serum ferritin, serum calcium, phosphorus, serum albumin, alkaline phosphatase, 25-OH vitamin D, and parathormone (PTH) levels. Results. There were 17 males and 19 females with mean age of 12.56 +/- 5.9 years. Hypocalcemia and hypophosphatemia were seen in 66.6% and 19.4%, respectively, while 25-OH vitamin D deficiency was present in 72.2% of thalassemic children and adolescents. Hypoparathyroidism was seen in 13.8% while hyperparathyroidism was detected in 8.3% of patients. There was direct correlation between serum phosphorus and ferritin levels (P < 0.05). No correlation was found between indirect bilirubin and skeletal parameters, calcium and parathyroid hormone (P > 0.05). Conclusions. Biochemical profile is significantly altered in patients with beta-thalassemia major and bone associated biochemical abnormalities like hypocalcaemia, 25-OH vitamin D deficiency, and hypophosphatemia are not uncommon in Pakistani patients with thalassemia major. PMID- 27006654 TI - A Comprehensive Updated Review of Pharmaceutical and Nonpharmaceutical Treatment for NAFLD. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the western world with prevalence of 20-33%. NAFLD comprises a pathological spectrum. Nonalcoholic fatty liver (NAFL) is at one end and consists of simple hepatic steatosis. On the contrary, nonalcoholic steatohepatitis (NASH) consists of steatosis, inflammation, and ballooning degeneration and can progress to cirrhosis. Despite the rising incidence, definitive treatment for NAFLD, specifically NASH, has not yet been established. Lifestyle modification with dietary changes combined with regular aerobic exercise, along with multidisciplinary approach including cognitive behavior therapy, has been shown to be an effective therapeutic option, even without a significant weight loss. Pioglitazone and vitamin E have shown to be most effective in NASH patients. Surgery and weight loss medication are effective means of weight loss but can potentially worsen NASH related fibrosis. Other agents such as n-3 polyunsaturated fatty acids, probiotics, and pentoxifylline along with herbal agent such as milk thistle as well as daily intake of coffee have shown potential benefits, but further well organized studies are definitely warranted. This review focuses on the available evidence on pharmaceutical and nonpharmaceutical therapy in the treatment and the prevention of NAFLD, primarily NASH. PMID- 27006659 TI - Synergistic Interaction of Methanol Extract from Canarium odontophyllum Miq. Leaf in Combination with Oxacillin against Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC 33591. AB - Canarium odontophyllum (CO) Miq. has been considered as one of the most sought after plant species in Sarawak, Malaysia, due to its nutritional and pharmacological benefits. This study aimed to evaluate the pharmacodynamic interaction of crude methanol and acetone extracts from CO leaves in combination with oxacillin, vancomycin, and linezolid, respectively, against MRSA ATCC 33591 as preliminary study has reported its potential antistaphylococcal activity. The broth microdilution assay revealed that both methanol and acetone extracts were bactericidal with Minimum Inhibitory Concentration (MIC) of 312.5 MUg/mL and 156.25 MUg/mL and Minimum Bactericidal Concentration (MBC) of 625 MUg/mL and 312.5 MUg/mL, respectively. Fractional Inhibitory Concentration (FIC) indices were obtained via the chequerboard dilution assay where methanol extract oxacillin, acetone extract-oxacillin, methanol extract-linezolid, and acetone extract-linezolid combinations exhibited synergism (FIC index <= 0.5). The synergistic action of the methanol extract-oxacillin combination was verified by time-kill analysis where bactericidal effect was observed at concentration of 1/8 * MIC of both compounds at 9.6 h compared to oxacillin alone. As such, these findings postulated that both extracts exert their anti-MRSA mechanism of action similar to that of vancomycin and provide evidence that the leaves of C. odontophyllum have the potential to be developed into antistaphylococcal agents. PMID- 27006660 TI - Sinus Balloon Dilation as Treatment for Acute Sphenoid Sinusitis with Impaired Vision for a Child. AB - This paper is about sinus balloon dilatation in treatment of acute left sphenoid sinusitis with left impaired vision in a child. Balloon catheter dilatation (BCD) of the sinus ostia is a new technique. It has been shown to be a minimally invasive technique to manage chronic sinusitis. However, this method is rarely used in the treatment of acute sinusitis. So far, we know of no reported cases of sinus balloon dilatation in treatment of this case, especially for children. PMID- 27006662 TI - Stem Cells, Inflammation, and Fibrosis. PMID- 27006663 TI - Attachment, Growth, and Detachment of Human Mesenchymal Stem Cells in a Chemically Defined Medium. AB - The manufacture of human mesenchymal stem cells (hMSCs) for clinical applications requires an appropriate growth surface and an optimized, preferably chemically defined medium (CDM) for expansion. We investigated a new protein/peptide-free CDM that supports the adhesion, growth, and detachment of an immortalized hMSC line (hMSC-TERT) as well as primary cells derived from bone marrow (bm-hMSCs) and adipose tissue (ad-hMSCs). We observed the rapid attachment and spreading of hMSC TERT cells and ad-hMSCs in CDM concomitant with the expression of integrin and actin fibers. Cell spreading was promoted by coating the growth surface with collagen type IV and fibronectin. The growth of hMSC-TERT cells was similar in CDM and serum-containing medium whereas the lag phase of bm-hMSCs was prolonged in CDM. FGF-2 or surface coating with collagen type IV promoted the growth of bm hMSCs, but laminin had no effect. All three cell types retained their trilineage differentiation capability in CDM and were detached by several enzymes (but not collagenase in the case of hMSC-TERT cells). The medium and coating did not affect detachment efficiency but influenced cell survival after detachment. CDM combined with cell-specific surface coatings and/or FGF-2 supplements is therefore as effective as serum-containing medium for the manufacture of different hMSC types. PMID- 27006661 TI - Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research. AB - Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs). The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs) are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research. PMID- 27006665 TI - Quality Assessment of Artemether-Lumefantrine Samples and Artemether Injections Sold in the Cape Coast Metropolis. AB - Most prescribers and patients in Ghana now opt for the relatively expensive artemether/lumefantrine rather than artesunate-amodiaquine due to undesirable side effects in the treatment of uncomplicated malaria. The study sought to determine the existence of substandard and/or counterfeit artemether-lumefantrine tablets and suspension as well as artemether injection on the market in Cape Coast. Six brands of artemether-lumefantrine tablets, two brands of artemether lumefantrine suspensions, and two brands of artemether injections were purchased from pharmacies in Cape Coast for the study. The mechanical properties of the tablets were evaluated. The samples were then analyzed for the content of active ingredients using High Performance Liquid Chromatography with a variable wavelength detector. None of the samples was found to be counterfeit. However, the artemether content of the samples was variable (93.22%-104.70% of stated content by manufacturer). The lumefantrine content of the artemether/lumefantrine samples was also variable (98.70%-111.87%). Seven of the artemether-lumefantrine brands passed whilst one failed the International Pharmacopoeia content requirements. All brands of artemether injections sampled met the International Pharmacopoeia content requirement. The presence of a substandard artemether lumefantrine suspension in the market should alert regulatory bodies to be more vigilant and totally flush out counterfeit and substandard drugs from the Ghanaian market. PMID- 27006664 TI - The Role of miRNAs in the Regulation of Pancreatic Cancer Stem Cells. AB - Pancreatic ductal adenocarcinoma is currently one of the deadliest cancers with low overall survival rate. This disease leads to an aggressive local invasion and early metastases and is poorly responsive to treatment with chemotherapy or chemoradiotherapy. Several studies have shown that pancreatic cancer stem cells (PCSCs) play different roles in the regulation of drug resistance and recurrence in pancreatic cancer. MicroRNA (miRNA), a class of newly emerging small noncoding RNAs, is involved in the modulation of several biological activities ranging from invasion to metastases development, as well as drug resistance of pancreatic cancer. In this review, we synthesize the latest findings on the role of miRNAs in regulating different biological properties of pancreatic cancer stem cells. PMID- 27006666 TI - Validity and Reliability of Published Comprehensive Theory of Mind Tests for Normal Preschool Children: A Systematic Review. AB - OBJECTIVE: Theory of mind (ToM) or mindreading is an aspect of social cognition that evaluates mental states and beliefs of oneself and others. Validity and reliability are very important criteria when evaluating standard tests; and without them, these tests are not usable. The aim of this study was to systematically review the validity and reliability of published English comprehensive ToM tests developed for normal preschool children. METHOD: We searched MEDLINE (PubMed interface), Web of Science, Science direct, PsycINFO, and also evidence base Medicine (The Cochrane Library) databases from 1990 to June 2015. Search strategy was Latin transcription of 'Theory of Mind' AND test AND children. Also, we manually studied the reference lists of all final searched articles and carried out a search of their references. Inclusion criteria were as follows: Valid and reliable diagnostic ToM tests published from 1990 to June 2015 for normal preschool children; and exclusion criteria were as follows: the studies that only used ToM tests and single tasks (false belief tasks) for ToM assessment and/or had no description about structure, validity or reliability of their tests. METHODological quality of the selected articles was assessed using the Critical Appraisal Skills Programme (CASP). RESULT: In primary searching, we found 1237 articles in total databases. After removing duplicates and applying all inclusion and exclusion criteria, we selected 11 tests for this systematic review. CONCLUSION: There were a few valid, reliable and comprehensive ToM tests for normal preschool children. However, we had limitations concerning the included articles. The defined ToM tests were different in populations, tasks, mode of presentations, scoring, mode of responses, times and other variables. Also, they had various validities and reliabilities. Therefore, it is recommended that the researchers and clinicians select the ToM tests according to their psychometric characteristics, validity and reliability. PMID- 27006667 TI - Zar Spirit Possession in Iran and African Countries: Group Distress, Culture Bound Syndrome or Cultural Concept of Distress? PMID- 27006668 TI - Prevalence and Predictors of Domestic-Violence towards Wives by their Psychiatric Hospitalized Husbands. AB - OBJECTIVE: Violence imposed on wives by their inpatient psychiatric husbands has not been studied yet. The current study surveyed the rates and predictors of violence committed by inpatient psychiatric husbands towards their wives. METHODS: A convenient sample of wives of 209 married male psychiatric inpatients completed a self-reported questionnaire. They were asked about physical, emotional, social and economic abuse. RESULTS: More than 80% of the husbands socially abused their wives; 73.0% of the wives had been regularly beaten by their husbands; the rate for humiliation was 77.2%; and only 14.1% of the wives reported that their sexual relationship with their husbands is with desire. Conclusion There is a dramatic high rate of different types of abuse toward wives by their inpatient psychiatric husbands. They are commonly victimized by their husbands. Moreover, different types of violence always co-occur. Future studies should consider this important issue which is unfortunately an ignored research area. PMID- 27006669 TI - Burden on Family Caregivers Caring for Patients with Schizophrenia. AB - OBJECTIVE: The aim of this study was to determine the prevalence of the burden reported by family caregivers of Patients with schizophrenia. METHODS: This cross sectional study involved face-to-face interviews with family caregivers of patients with schizophrenia. Using convenience sampling, 225 caregivers were selected from Farshchian psychiatry Hospital in Hamadan, Iran from July to September 2012. Measures included patients and caregivers' demographic variables and caregivers' burden using the Zarit Burden Interview (ZBI). Data were analyzed by SPSS-18 with Pearson correlation and t-test. RESULTS: Using the ZBI, we found that 7.6% of the caregivers experienced "no to low" burden, 23.5% "mild to moderate", 41.8% "moderate to severe" and 27.1% "severe" burden. The mean average score of the responses to ZBI was 51.73 (SD: +/- 18.23). The level of burden experienced was significantly associated with age, gender, and educational level, relation to care recipient, caregiving duration and duration of schizophrenia illness. CONCLUSION: ? ?Mental health professionals need to develop more innovative programs for families of schizophrenic patients. Furthermore, as a replacement for supporting the families and easing their burdens, it may be more effective to include them in the health care team by assigning specific tasks and providing the required resources to them to perform such tasks. . PMID- 27006670 TI - The Persian Checklist of Pleasant Events (PCPE): Development, Validity and Reliability. AB - OBJECTIVE: Experiencing pleasant events during daily life has a significant positive role in the personal mental health and acts as a keystone for "behavioral activation" (BA) interventions. There are serious differences in the pleasant event schedules in different cultures and countries. We aimed to develop a Persian checklist of pleasant events (PCPE) to provide and validate a culturally compatible checklist for Iranians. METHODS: To develop a checklist of pleasant events, inspired by Pleasant Events Schedule (PES) (MacPhillamy & Lewinsohn, 1982), we held three focused group discussions with 24 normal healthy participants from both genders (female = 12) and asked them to mention as much pleasant events as possible. When the list reached saturation level, the inappropriate items with respect to legal, cultural and religious concerns were omitted. The final checklist of PCPE consists of two subscales: Frequency (frequency of events during last month) and pleasantness (perceived pleasantness of events). The total score consists of frequency multiplied by pleasantness. To test the reliability and validity of the checklist, the PCPE, Depression, Anxiety and Stress Scale (DASS), the Persian version of WHO Quality of Life and the Demographic Questionnaire were administered in a sample of 104 participants (50 male and 54 female). RESULTS: Frequency, pleasantness and the total scores of PCPE showed high levels of internal consistency (Cronbach's alpha, .976, .976 & .974, respectively). Further support for the convergent validity of the PCPE was obtained via moderate negative correlations with depression, anxiety, stress scores in DASS and positive correlation with quality of life as well as respondent's perceived happiness. There were negative correlations between frequency, pleasantness and total scores and age of the participants (Pearson correlation coefficient, r = -.194, p<0.05; r = -.270, p<0.01 & r = -.234, p<0.05, respectively). Conclusion ?:? PCPE as an assessment tool has shown to have good reliability and validity among Iranians. Further steps should be taken to validate this instrument in different psychopathologies such as depression, addiction and obesity. . PMID- 27006671 TI - The Validity and Reliability of the Persian Version Test of Mobile Phone Dependency (TMD). AB - OBJECTIVE: ? ?Despite the fact that the mobile phone has become a pervasive technology of our time, little research has been done on mobile dependency. A valid and reliable assessment instrument corresponding to the Persian culture is essential. This study aimed to describe the construction and validation of the Persian version of TMD (Test of Mobile phone Dependency) to assess the addictive use of mobile phone. METHODS: This was a cross-sectional study, for which data were collected from 350 students who were studying at Tehran universities. Sampling method was quota sampling. The participants anonymously completed the demographic questionnaire, and CPDQ as a valid questionnaire and gold standard. Finally, clinical interview [based on DSM-IV-TR] was performed. To analyze the data, concurrent validity, factor analysis, internal consistency (Cronbachalpha), split half; test-retest and ROC Curve by SPSS18 Software were used. RESULTS: As a result of the reliability analysis and factor analysis by principal component and Varimax rotation, three factors ("salient", "preoccupation" and "Spend a lot of time and money") for both male and female participants were extracted. Internal consistency (Cronbach's alpha) of the TMD was .92 (Cronbach alpha of the factors is .88, .82, and .84, respectively). The test-retest correlation of the TMD was .56.The best cut off point for this questionnaire (TMD) is 38. CONCLUSION: The TMD proved to have an acceptable internal consistency with adequate factor models to assess the extent of problems caused by the "misuse" of the mobile phone in the Iranian society. Therefore, it can be concluded that the Persian version of the test was reliable and valid; however, further analysis is needed.. PMID- 27006672 TI - Work Predictors of Lapse in Patients under Treatment of Methadone Maintenance Therapy. AB - BACKGROUND: Addiction to narcotics can cause serious problems and monetary losses. Therapeutic success can be predicted through identifying lapse risk factors. OBJECTIVE: Determining Job Risk Factor of Lapse. METHODS: This was a cross sectional study on 351 addicts visiting five methadone clinics. A Data collection sheet consisting of questions on demographic and job information was filled up through direct interviews. Information relating to lapse in the first month was analyzed. RESULTS: The mean (SD) age of the participants was 40(12) years; of them, 74% were employed, of whom 34% had lapsed. A relationship was noticed between education qualification (secondary school compared with higher and lower education) and lapse (p = .04), and also between type of drug abuse (amphetamine) and lapse (p = .001). CONCLUSION: ? ? Lapse was more dependent on type of drug abused, and employment had a protective role, with no correlation with the type of job and other job conditions. Non-work factors mediated/suppressed the role of occupational conditions.. PMID- 27006673 TI - Maternal self-efficacy and feeding practices in children aged 3-6 years. AB - OBJECTIVE: Nutrition in childhood has an important role in current and adulthood health. Recent studies have shown that the mother's lifestyle has an important role in the methods used by mother to feed child. This paper aimed to investigate the association between mother's weight efficacy lifestyle with feeding practices in children aged 3- 6 years. MATERIALS AND METHODS: In this cross-sectional study which was carried out in 30 primary schools of Rasht (Iran) in 2012, 165 mothers with children aged 3-6 years were participated. Mothers reported their own and their child's demographics. Aspects of mother's weight efficacy lifestyle and mother's control practices were assessed using Weight Efficacy Lifestyle (WEL) questionnaire and Comprehensive Feeding Practices questionnaire (CFPQ) respectively. Height and weight of mothers participated in the study were measured. The role of mother's weight efficacy in predicting child's feeding practices was assessed using linear regression. RESULTS: RESULTS showed that mother's weight efficacy was related to child feeding practices. The mothers with similar weight efficacy lifestyle applied similar methods in child nutrition. Mothers with better weight efficacy used more encourage balance and variety, environmental control, child involvement and less emotion regulation using foods. CONCLUSION: ? ? The result of the study showed that maternal lifestyle was associated with child feeding practices.. PMID- 27006674 TI - Prevalence of Conduct Disorder in the Middle East: A Systematic Review and Meta Analysis Protocol. AB - BACKGROUND: The global burden of conduct disorder is a major public health concern. Although there are different reports on the prevalence of conduct disorder in different Middle Eastern countries, to date, no research has reviewed them. Therefore, we aimed to conduct a systematic review and meta-analysis on the literature and present the prevalence of conduct disorder among children and adolescents in Middle Eastern countries. METHODS: Those cross-sectional studies with any type of random or non-random sampling, which described the prevalence of conduct disorder prior to age of 18, for at least one gender in the general or school-based populations who resided in Middle Eastern countries were included in this review. The scientific databases of PubMed, Scopus, Google Scholar, Index Medicus for the Eastern Mediterranean Region (IMEMR), Islamic World Science Citation Center (ISC), and Grey Literature including conference proceedings, and hand searching of key journals were searched from 1995 to the end of 2014. Two reviewers assessed the quality of the included studies independently and extracted the relevant data. DISCUSSION: This review provided a picture of different frequencies of conduct disorder in Middle Eastern countries and analyzed the sources of heterogeneity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014014996. PMID- 27006675 TI - Quadrigeminal plate lipoma presenting with Psychosis: A case report with review of literature. PMID- 27006676 TI - The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study. AB - In Kampo medicine, two different formulas are effective for treating dysmenorrhea tokishakuyakusan and keishibukuryogan; however, the criteria by which specialists select the appropriate formula for each patient are not clear. We compared patients treated with tokishakuyakusan and those with keishibukuryogan and proposed a predictive model. The study included 168 primary and secondary dysmenorrhea patients who visited the Kampo Clinic at Keio University Hospital. We collected clinical data from 128 dysmenorrhea patients, compared the two patient groups and selected significantly different factors as potential predictors, and used logistic regression to establish a model. An external validation was performed using 40 dysmenorrhea patients. Lightheadedness, BMI < 18.5, and a weak abdomen were significantly more frequent in the tokishakuyakusan group; tendency to sweat, heat intolerance, leg numbness, a cold sensation in the lower back, a strong abdomen, and paraumbilical tenderness and resistance were more frequent in the keishibukuryogan group. The final model fitted the data well. Internally estimated accuracy was 81.2%, and a leave-one-out cross validation estimate of accuracy was 80.5%. External validation accuracy was 85.0%. We proposed a model for predicting the use of two Kampo formulas for dysmenorrhea, which should be validated in prospective trials. PMID- 27006677 TI - The Effect of Vinpocetine on Human Cytochrome P450 Isoenzymes by Using a Cocktail Method. AB - Vinpocetine is a derivative of the alkaloid vincamine, which had been prescribed for chronic cerebral vascular ischemia and acute ischemic stroke or used as a dietary supplement for its several different mechanisms of biological activities. However, information on the cytochrome P450 (CYP) enzyme-mediated drug metabolism has not been previously studied. The present study was performed to investigate the effects of vinpocetine on CYPs activity, and cocktail method was used, respectively. To evaluate the effects of vinpocetine on the activity of human CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, human liver microsomes were utilized to incubate with the mixed CYPs probe substrates and the target components. The results indicate that vinpocetine exhibited weak inhibitory effect on the CYP2C9, where the IC50 value is 68.96 MUM, whereas the IC50 values for CYP3A4, CYP2C19, CYP2D6, and CYP2E1 were all over range of 100 MUM, which showed that vinpocetine had no apparent inhibitory effects on these CYPs. In conclusion, the results indicated that drugs metabolized by CYP2C9 coadministrated with vinpocetine may require attention or dose adjustment. PMID- 27006678 TI - Antimutagenic Compounds of White Shrimp (Litopenaeus vannamei): Isolation and Structural Elucidation. AB - According to the World Health Organization, cancer is the main cause of mortality worldwide; thus, the search of chemopreventive compounds to prevent the disease has become a priority. White shrimp (Litopenaeus vannamei) has been reported as a source of compounds with chemopreventive activities. In this study, shrimp lipids were extracted and then fractionated in order to isolate those compounds responsible for the antimutagenic activity. The antimutagenic activity was assessed by the inhibition of the mutagenic effect of aflatoxin B1 on TA98 and TA100 Salmonella tester strains using the Ames test. Methanolic fraction was responsible for the highest antimutagenic activity (95.6 and 95.9% for TA98 and TA100, resp.) and was further separated into fifteen different subfractions (M1 M15). Fraction M8 exerted the highest inhibition of AFB1 mutation (96.5 and 101.6% for TA98 and TA100, resp.) and, after further fractionation, four subfractions M8a, M8b, M8c, and M8d were obtained. Data from (1)H and (13)C NMR, and mass spectrometry analysis of fraction M8a (the one with the highest antimutagenic activity), suggest that the compound responsible for its antimutagenicity is an apocarotenoid. PMID- 27006680 TI - Antibodies to the DNA-directed RNA polymerase II subunit RPB1 occur with highest frequency in centenarians. AB - BACKGROUND: Recently, phage display technology has made it possible to define the circulating repertoire of humoral immunity. This study was designed to define the circulating antibodies specific to centenarians. RESULTS: We used a phage displayed combinatorial peptide library to screen for peptides (YSATLRY and YSPTLFY) that preferentially react with the IgG fraction of centenarians aged 100 105 years. Centenarian sera binds to YSATLRY and YSPTLFY with higher frequency than that of healthy volunteers aged 60-79 years or healthy volunteers younger than or equal to 43 years of age. We prepared polyclonal antibodies to YSATLRY from human sera to immunoprecipitate the native antigen, which was identified as the carboxy-terminal domain (CTD) of DNA-directed RNA polymerase II subunit RPB1. The RBP1 CTD contains multiple YSPTSPS repeats, which are significantly homologous to YSATLRY and YSPTLFY. The immunoprecipitated RPB1 had significantly slower mobility than did RPB1 in cell lysates, and the polyclonal antibodies reacted with CTD peptide, depending on the phosphorylation pattern. Therefore, it appears that the polyclonal antibodies preferentially bind to highly phosphorylated RPB1. We also confirmed that human monoclonal antibodies reactive to both YSATLRY and YSPTLFY bound to the phosphorylated YSPTSPS motif. CONCLUSIONS: This study showed that centenarians possess IgG antibodies that are reactive to YSATLRY and YSPTLFY, mimicking the phosphorylated form of the YSPTSPS motif (CTD of RPB1), at a much higher frequency than that of the average population. PMID- 27006679 TI - Acupuncture Treatment of Lateral Elbow Pain: A Nonrandomized Pilot Study. AB - In planning for a large-scale multicenter trial to evaluate the effect of acupuncture for the treatment of lateral elbow pain, a pilot study was conducted. This was a prospective, investigator- and patient-blinded, nonrandomized, placebo controlled trial. Subjects were evaluated at baseline, before fourth, seventh, and ninth treatment, and at a two-week posttreatment follow-up. The treatment group received unilateral acupuncture at LI 10 and LI 11 at the affected side with manual needle manipulation; the control group received sham-laser acupuncture at the same acupoints. Measures included (i) disabilities of the arm, shoulder, and hand (DASH) questionnaire, (ii) pain-free grip strength (PFGS), and (iii) a visual analogue scale (VAS) for pain. Significant differences in DASH score, PFGS, and VAS between treatment and control group were found at the ninth treatment (n = 20 for each group, P < 0.05). Only DASH showed significant differences compared to the control for all the measurement time points after treatment commenced and appears to be a sensitive and appropriate primary outcome measure for the future multisite trial. Results from this pilot study provided relevant information about treatment efficacy, credibility of control treatment, and sensitivity of different outcome measures for the planning of the future trial. PMID- 27006681 TI - Acute phase of aortic dissection: a pilot study on CD40L, MPO, and MMP-1, -2, 9 and TIMP-1 circulating levels in elderly patients. AB - BACKGROUND: Acute aortic dissection (AAD) is an event which may be rapidly fatal without early diagnosis and treatment. Aging is one of the main risk factors that could leading to AAD. To date, no specific biomarkers are available to increase the speed of diagnosis. CD40 ligand (CD40L), myeloperoxidase (MPO), matrix metalloproteinase (MMP)-1, -2, -9 and metallopeptidase tissue inhibitor 1 (TIMP 1) are biologically related molecules which integrate inflammation, tissue injury and remodeling, all events associated to AAD. Our is a pilot study to evaluate whether circulating levels of these molecules may be used as potential biomarkers in timely diagnosis of AAD. RESULTS: Within 24 h of symptom onset, circulating CD40L, MPO, MMP-1,-2,-9 and TIMP-1 were quantified by enzyme-linked immunosorbent assays in 22 patients (40-86 years of age) with AAD of ascending aorta (type A according to Stanford classification) and 11 patients with AAD of descending aorta (type B). 30 healthy individuals age matched were used as control group compared to controls, both type A and B AAD patients had higher CD40L (p < 0.001) and MPO (p < 0.01) levels. MMP-1 was higher in the overall AAD group (p < 0.01). After Stanford classification, type A group had increased level compared to both control and type B (p < 0.01 and p < 0.05, respectively). TIMP-1 was higher in both A and B groups compared to controls (p < 0.001). No differences were observed in MMP-2 and MMP-9 levels. CONCLUSIONS: The simultaneous evaluation of CD40L, MPO and MMP-1 and TIMP-1, which may contribute to structural changes in aortic tissue in AAD patients, seems to be a novel promising diagnostic panel. PMID- 27006682 TI - Factors associated with HIV viral load "blips" and the relationship between self reported adherence and efavirenz blood levels on blip occurrence: a case-control study. AB - BACKGROUND: The uncertain etiology of HIV viral load (VL) blips may lead to increased use of clinical resources. We evaluated the association of self reported adherence (SRA) and antiretroviral (ART) drug levels on blip occurrence in US Military HIV Natural History Study (NHS) participants who initiated the single-tablet regimen efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS: ART-naive NHS participants started on EFV/FTC/TDF between 2006 and 2013 who achieved VL suppression (<50 copies/mL) within 12 months and had available SRA and stored plasma samples were included. Participants with viral blips were compared with those who maintained VL suppression without blips. Untimed EFV plasma levels were evaluated on consecutive blip and non-blip dates by high performance liquid chromatography, with a level >=1 mcg/mL considered therapeutic. SRA was categorized as >=85 or <85 %. Descriptive statistics were performed for baseline characteristics and univariate and multivariate Cox proportional hazard models were used to assess the relationship between covariates and blip occurrence. RESULTS: A total of 772 individuals met inclusion criteria, including 99 (13 %) blip and 673 (87 %) control participants. African American was the predominant ethnicity and the mean age was 29 years for both groups. SRA >= 85 % was associated with therapeutic EFV levels at both blip and non-blip time points (P = 0.0026); however no association was observed between blips and SRA or EFV levels among cases. On univariate analysis of cases versus controls, blips were associated with higher mean pre-treatment VL (HR 1.45, 95 % CI 1.11-1.89) and pre-treatment CD4 count <350 cells/uL (68.1 vs 49.7 %). Multivariate analysis also showed that blips were associated with a higher mean VL (HR 1.42, 95 % CI 1.08-1.88; P = 0.0123) and lower CD4 count at ART initiation, with CD4 >=500 cells/uL having a protective effect (HR 0.45, 95 % CI 0.22-0.95; P = 0.0365). No association was observed for demographic characteristics or SRA. CONCLUSION: Blips are commonly encountered in the clinical management of HIV-infected patients. Although blip occurrence was not associated with SRA or EFV blood levels in our study, blips were associated with HIV-related factors of pre-ART high VL and low CD4 count. Additional studies are needed to determine the etiology of blips in HIV-infected patients. PMID- 27006683 TI - Mesoscale morphology at nanoscale resolution: serial block-face scanning electron microscopy reveals fine 3D detail of a novel silk spinneret system in a tube building tanaid crustacean. AB - BACKGROUND: The study of morphology is experiencing a renaissance due to rapid improvements in technologies for 3D visualization of complex internal and external structures. But 3D visualization of the internal structure of mesoscale objects - those in the 10-1000 MUm range - remains problematic. They are too small for microCT, many lack suitable specific fluorescent markers for confocal microscopy, or they require labor-intensive stacking and smoothing of individual TEM images. Here we illustrate the first comprehensive morphological description of a complete mesoscale biological system at nanoscopic resolution using ultra modern technology for 3D visualization - serial block-face scanning electron microscopy (SBF-SEM). The SBF-SEM machine combines an in-chamber ultramicrotome, which creates a serial array of exposed surfaces, with an SEM that images each surface as it is exposed. The serial images are then stacked automatically by 3D reconstruction software. We used SBF-SEM to study the spinneret (thread producing) system of a small, tube-dwelling crustacean that weaves tubes of silk. Thread-producing ability is critical for the survival of many small-bodied animals but the basic morphology of these systems remains mysterious due to the limits of traditional microscopy. RESULTS: SBF-SEM allowed us to describe - in full 3D - well-resolved components (glands, ducts, pores, and associated nerves and muscles) of the spinneret system in the thoracic legs and body segments of Sinelobus sp. (Crustacea, Peracarida, Tanaidacea), a tube-building tanaid only 2 mm in body length. The 3D reconstruction by SBF-SEM revealed at nanoscale resolution a unique structure to the gland and duct systems: In each of three thread-producing thoracic segments, two separate ducts, derived from two separate glands located in the body, run through the entire leg and merge at the leg tip just before the spinneret pore opening. We also resolved nerves connecting to individual setae, spines and pores on the walking legs, and individual muscles within each leg segment. CONCLUSIONS: Our results significantly expand our understanding of the diversity of spinneret systems in the Crustacea by providing the first well-resolved view of spinneret components in the peracarid crustacean order, Tanaidacea. More significantly, our results reveal the great power of SBF SEM technology for comprehensive studies of the morphology of microscopic animals. PMID- 27006684 TI - Work-related diabetes distress among Finnish workers with type 1 diabetes: a national cross-sectional survey. AB - BACKGROUND: Diabetes distress is common among people with type 1 diabetes, but knowledge is scarce regarding the perceived burden of reconciling work with this disease. This cross-sectional study investigated work-related diabetes distress among Finnish workers with type 1 diabetes. METHODS: A questionnaire was mailed to 2500 randomly sampled 18- to 65-year-old Finns with type 1 diabetes; 49.3 % responded. Work-related diabetes distress was measured by combining worry and exhaustion in reconciling work with diabetes. Self-perceived work-related diabetes distress was evaluated in the context of physical and psychosocial work conditions, job demands, work ability, general stress, diabetes acceptance, glycosylated hemoglobin (HbA1c) level, high blood glucose maintenance at work, and depressive symptoms. The data were analyzed with the use of cross-tabulation, chi-square tests, ANOVA analysis, Spearman correlation coefficients, and structural equation modeling. RESULTS: Of the respondents, 70 % experienced work related diabetes distress. Problems with physical work conditions (beta = 0.27), work ability (beta = -0.21), difficulty in accepting diabetes (beta = 0.18), and job demands (beta = 0.14) were found to be associated with work-related diabetes distress. This distress was strongly associated with the maintenance of a high blood glucose level at work (beta = 0.34). In turn, a high blood glucose level at work was associated with a high HbA1c level (beta = 0.29). Work-related diabetes distress and depressive symptoms had a bi-directional association (beta = 0.06 and beta = 0.14). Difficulty accepting diabetes had three-dimensional associations: work-related diabetes distress (beta = 0.18), depressive symptoms (beta = 0.13), and high HbA1c level (beta = 0.12). There was no notable association between work-related diabetes distress and general stress. CONCLUSIONS: Work-related diabetes distress is common among workers with type 1 diabetes, and it may influence metabolic control. This stress could be prevented by adapting physical work conditions. People with type 1 diabetes should also be encouraged to pursue their full educational potential, and psychological support should be provided for those with difficulty accepting their diabetes. PMID- 27006685 TI - Daily commuting to work is not associated with variables of health. AB - BACKGROUND: Commuting to work is thought to have a negative impact on employee health. We tested the association of work commute and different variables of health in German industrial employees. METHODS: Self-rated variables of an industrial cohort (n = 3805; 78.9 % male) including absenteeism, presenteeism and indices reflecting stress and well-being were assessed by a questionnaire. Fasting blood samples, heart-rate variability and anthropometric data were collected. Commuting was grouped into one of four categories: 0-19.9, 20-44.9, 45 59.9, >=60 min travelling one way to work. Bivariate associations between commuting and all variables under study were calculated. Linear regression models tested this association further, controlling for potential confounders. RESULTS: Commuting was positively correlated with waist circumference and inversely with triglycerides. These associations did not remain statistically significant in linear regression models controlling for age, gender, marital status, and shiftwork. No other association with variables of physical, psychological, or mental health and well-being could be found. CONCLUSIONS: The results indicate that commuting to work has no significant impact on well-being and health of German industrial employees. PMID- 27006686 TI - Determinants of suboptimal breastfeeding practice in Debre Berhan town, Ethiopia: a cross sectional study. AB - BACKGROUND: Optimal breastfeeding is inextricably linked to the achievement of Millennium Development Goals (MDGs) of eradicating extreme poverty and hunger, reducing child mortality and improving maternal health. Breastfeeding is safe, promotes sensory and cognitive development and contains antibodies that protect infants from common childhood illnesses. The objective of this study was to assess suboptimal breastfeeding and its determinants factors among mothers who have children below 23 months old in Debre Berhan, Ethiopia. METHODS: A community based cross sectional study was conducted from 1 March 2015 until 30 March 2015. Five hundred forty eight mothers were included in the study using a two stage sampling technique. The data was collected by trained data collectors through pretested semi structured questionnaire. The collected data were cleaned, coded, entered and then analyzed using SPSS version 20 windows program. Descriptive statistics, binary and multivariable regression analysis with 95 % confidence interval was carried out and p value less than 0.05 used to determine the significant association. Late initiation of breastfeeding was defined as initiation of breastfeeding after one hour of delivery while early cessation of breastfeeding was to stop breastfeeding before 24 months of age. According to World Health Organization exclusive breastfeeding was defined as the practice of feeding breast milk only, including expressed breast milk, to infants and excluding water, other liquids, breast milk substitutes, and solid foods. Vitamin drops, minerals, oral rehydrating solution (ORS) and medicines may be given. RESULTS: The prevalence of late initiation of breastfeeding, not exclusively breastfeeding and early cessation of breastfeeding were 17.5 % (95 % Confidence Interval [CI] 15.2 %, 19.4), 49.8 % (95 % CI 46.3, 50.5) and 12.8 % (95 % CI 11.7, 14.1) respectively. Birth at home was significantly associated with late initiation of breastfeeding (Adjusted Odds Ratio [AOR] 3.0; 95 % CI 1.5, 6.0). No advice during antenatal care was a predictor of not exclusively breastfeeding (AOR1.7; 95 % CI 1.2, 2.5). Being illiterate (AOR 3.2; 95 % CI 1.2, 8.3) and no advice during antenatal care about breastfeeding (AOR 1.9; 95 % CI 1.0. 3.4) were significantly associated with early cessation of breastfeeding. CONCLUSION: Educational status, age, antenatal and postnatal follow up, resident and place of delivery were predictors of suboptimal breastfeeding. Integrated and targeted interventions were recommended to achieve a better outcome in minimizing the late initiation, non-exclusive and early cessation of breastfeeding. PMID- 27006687 TI - Kinetics of cytochrome P450 enzymes for metabolism of sodium tanshinone IIA sulfonate in vitro. AB - BACKGROUND: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA for treating cardiovascular disorders. The roles of cytochrome P450 enzymes (CYPs) in the metabolism of STS have remained unclear. This study aims to screen the main CYPs for metabolism of STS and study their interactions in vitro. METHODS: Seven major CYPs were screened for metabolism of STS by human liver microsomes (HLMs) or recombinant CYP isoforms. Phenacetin (CYP1A2), coumarin (CYP2A6), tolbutamide (CYP2C9), metoprolol (CYP2D6), chlorzoxazone (CYP2E1), S-mephenytoin (CYP2C19), and midazolam (CYP3A4) were used as probe substrates to determine the potential of STS in affecting CYP-mediated phase I metabolism in humans. Enzyme kinetic studies were performed to investigate the modes of inhibition of the enzyme-substrate interactions by GraphPad Prism Enzyme Kinetic 5 Demo software. RESULTS: Sodium tanshinone IIA sulfonate inhibited the activity of CYP3A4 in a dose-dependent manner by the HLMs and CYP3A4 isoform. The K m and V max values of STS were 54.8 +/- 14.6 uM and 0.9 +/- 0.1 nmol/mg protein/min, respectively, for the HLMs and 7.5 +/- 1.4 uM and 6.8 +/- 0.3 nmol/nmol P450/min, respectively, for CYP3A4. CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, and CYP2C19 showed minimal or no effects on the metabolism of STS. CONCLUSION: This in vitro study showed that STS mainly inhibited the activities of CYP3A4. PMID- 27006688 TI - The severe traumatic brain injury in Austria: early rehabilitative treatment and outcome. AB - BACKGROUND: Severe traumatic brain injury (TBI) is a great economical and logistic problem in the health care system which reduces the quality of life and productivity of the patient. The purpose of this study is to evaluate the outcome of patients after severe brain trauma according to the course of their rehabilitation. METHODS: Patients with TBI were divided into three groups. Group A; after early rehabilitation (n = 16), B; following a standard rehabilitation procedure after work accidents (n = 34) and C; undergone standard rehabilitation procedure after accidents at home (n = 12). Glasgow Coma Scale (GCS), Post traumatic amnesia (PTA) during acute care, Glasgow Outcome Scale Extended (GOSE) and Functional Independence Measurement (FIM) were measured before and after rehabilitation. Long-term outcomes (12 months post injury) were measured with the Community Integration Questionnaire (CIQ). RESULTS: Group A showed a significantly shorter time span from hospital admission until rehabilitation center admission than B and C (p < 0.001). PTA was significantly lower in group B than in group A (p = 0.038). GOSE of patients within group C was significantly lower (p = 0.004) at hospital discharge. FIM was significantly higher in B (p = 0.005) at the time of admission to rehabilitation center. At the time of discharge FIM showed no significant differences between the groups. CIQ showed a trend to improving scores in group A. CONCLUSION: Despite the similar level of severity of TBI and outcome prognosis group A showed the best rehabilitation effect and long-term outcome. PMID- 27006689 TI - Inhibition of lignin-derived phenolic compounds to cellulase. AB - BACKGROUND: Lignin-derived phenolic compounds are universal in the hydrolysate of pretreated lignocellulosic biomass. The phenolics reduce the efficiency of enzymatic hydrolysis and increase the cost of ethanol production. We investigated inhibition of phenolics on cellulase during enzymatic hydrolysis using vanillin as one of the typical lignin-derived phenolics and Avicel as cellulose substrate. RESULTS: As vanillin concentration increased from 0 to 10 mg/mL, cellulose conversion after 72-h enzymatic hydrolysis decreased from 53 to 26 %. Enzyme deactivation and precipitation were detected with the vanillin addition. The enzyme concentration and activity consecutively decreased during hydrolysis, but the inhibition degree, expressed as the ratio of the cellulose conversion without vanillin to the conversion with vanillin (A 0 /A), was almost independent on hydrolysis time. Inhibition can be mitigated by increasing cellulose loading or cellulase concentration. The inhibition degree showed linear relationship with the vanillin concentration and exponential relationship with the cellulose loading and the cellulase concentration. The addition of calcium chloride, BSA, and Tween 80 did not release the inhibition of vanillin significantly. pH and temperature for hydrolysis also showed no significant impact on inhibition degree. The presence of hydroxyl group, carbonyl group, and methoxy group in phenolics affected the inhibition degree. CONCLUSION: Besides phenolics concentration, other factors such as cellulose loading, enzyme concentration, and phenolic structure also affect the inhibition of cellulose conversion. Lignin blocking agents have little effect on the inhibition effect of soluble phenolics, indicating that the inhibition mechanism of phenolics to enzyme is likely different from insoluble lignin. The inhibition of soluble phenolics can hardly be entirely removed by increasing enzyme concentration or adding blocking proteins due to the dispersity and multiple binding sites of phenolics than insoluble lignin. PMID- 27006690 TI - Crystal structure and biochemical characterization of the recombinant ThBgl, a GH1 beta-glucosidase overexpressed in Trichoderma harzianum under biomass degradation conditions. AB - BACKGROUND: The conversion of biomass-derived sugars via enzymatic hydrolysis for biofuel production is a challenge. Therefore, the search for microorganisms and key enzymes that increase the efficiency of the saccharification of cellulosic substrates remains an important and high-priority area of study. Trichoderma harzianum is an important fungus known for producing high levels of cellulolytic enzymes that can be used for cellulosic ethanol production. In this context, beta glucosidases, which act synergistically with cellobiohydrolases and endo-beta-1,4 glucanases in the saccharification process, are potential biocatalysts for the conversion of plant biomass to free glucose residues. RESULTS: In the present study, we used RNA-Seq and genomic data to identify the major beta-glucosidase expressed by T. harzianum under biomass degradation conditions. We mapped and quantified the expression of all of the beta-glucosidases from glycoside hydrolase families 1 and 3, and we identified the enzyme with the highest expression under these conditions. The target gene was cloned and heterologously expressed in Escherichia coli, and the recombinant protein (rThBgl) was purified with high yields. rThBgl was characterized using a comprehensive set of biochemical, spectroscopic, and hydrodynamic techniques. Finally, we determined the crystallographic structure of the recombinant protein at a resolution of 2.6 A. CONCLUSIONS: Using a rational approach, we investigated the biochemical characteristics and determined the three-dimensional protein structure of a beta glucosidase that is highly expressed by T. harzianum under biomass degradation conditions. The methodology described in this manuscript will be useful for the bio-prospection of key enzymes, including cellulases and other accessory enzymes, for the development and/or improvement of enzymatic cocktails designed to produce ethanol from plant biomass. PMID- 27006691 TI - Using the beta-glucosidase catalyzed reaction product glucose to improve the ionic liquid tolerance of beta-glucosidases. AB - BACKGROUND: Pretreating biomass with ionic liquids (IL) increases enzyme accessibility and cellulose is typically recovered through precipitation with an anti-solvent. An industrially feasible pretreatment and hydrolysis process requires robust cellulases that are stable and active in the presence of either small amounts of ILs co-precipitated with recovered cellulose or for saccharifications in the presence of IL. beta-glucosidase (BG) hydrolyzes cellobiose into two molecules of glucose (Glc) and is the last step of biomass hydrolysis. These enzymes are prone not only to product inhibition by glucose but also to inactivation by ILs. With increasing interest in IL-based pretreatment methods, there is increasing focus toward a search for Glc-tolerant and IL tolerant BG. RESULTS: We identified a BG belonging to the GH1 family, H0HC94, encoded in Agrobacterium tumefaciens 5A, and cloned and overexpressed the protein in Escherichia coli. H0HC94 exhibited high enzymatic activity with beta glycosidic substrates (248 umol/min/mg on pNPGlc and 262 umol/min/mg on cellobiose) and tolerant to Glc (apparent K i = 686 mM). Further evidence of Glc based stabilization came from the increase in melting temperature of H0HC94, with increasing Glc concentrations. The half-life of H0HC94 also increased between 2- and 20-fold in the presence of increasing concentrations of Glc. In the presence of 0.9 M of different [C2mim]-based ionic liquids, the specific activity of H0HC94 decreased by around 20-30 %. However, the addition of 100 mM glucose to the IL-enzyme mix resulted in a more stable enzyme as evidenced by the slight recovery of H0HC94 melting temperature and up to tenfold increase in half-life. This higher stability came at a cost of 2-10 % decrease in specific activity. The steady-state kinetic analyses for a subset of the ionic liquids tested indicate that the enzyme undergoes uncompetitive inhibition by glucose and ionic liquid, indicating the possibility of binding of the ionic liquid and glucose to the enzyme-substrate complex. CONCLUSIONS: H0HC94 is a Glc-stabilized BG that is also tolerant up to 0.9 M concentrations of different IL's and indicates the possibilities of using an IL-Glc-based cellulose solvent that displays enzyme compatibility. PMID- 27006692 TI - A pilot proof-of-principle study to compare fresh and vitrified cycle preimplantation genetic screening by chromosome microarray and next generation sequencing. AB - BACKGROUND: Single embryo transfer (SET) has been utilized as a strategy to reduce the chance of multifetal gestations in in vitro fertilization (IVF) but lower pregnancy rate remains a concern. Recent studies showed that favorable outcome regarding SET can be achieved by selecting embryos with "more normal" genetic components. We explored the use of rapid array comparative genomic hybridization (aCGH) to select blastocysts for fresh SET and compared with the protocols adopting vitrified (ultrarapidly frozen) embryo transfer cycle. Validation of the rapid protocol of aCGH and comparison of the result with the regular protocol of aCGH and next generation sequencing (NGS) are also performed. RESULTS: First-time IVF patients with normal karyotype (n = 21) were enrolled for elective fresh SET cycle (n = 8; designated as fresh SET group) or vitrified embryo transfer cycle (n = 13; designated as vitrified ET group) coupling with comprehensive chromosomal screening by a 9-h rapid aCGH from Day 5 trophectoderm (TE) biopsy. In fresh SET group, 86 blastocysts (10.8 blastocysts/patient) were biopsied and analyzed. Aneuploidy was detected in 53.5 % (46/86) of the biopsied blastocysts. All patients had a single embryo transferred on the following day. The clinical pregnancy rate was 87.5 % (7/8) and the ongoing pregnancy rate was 62.5 % (5/8). In vitrified ET group, 58 blastocysts (4.5 blastocysts/patient) were biopsied and 56 blastocysts were analyzed. Aneuploidy was detected in 39.3 % (22/56) of biopsies. The patients accepted for SET or double embryos transfer (DET) in non-stimulated cycles. The clinical pregnancy rate and the ongoing pregnancy rate was 76.9 % (10/13) and 53.8 % (7/13) respectively. Spontaneous abortions occurred in both of the two patient groups. In the series of fresh SET group, no twin pregnancy was noted and at least one healthy baby had been born at gestational age (GA) 37(+6) weeks when submission. The results of PGS by rapid aCGH, regular aCGH and NGS were comparable in most occasions. CONCLUSION: This study evaluates the use of rapid aCGH to select blastocysts for fresh SET and demonstrates its feasibility in a real clinical IVF program. A successful livebirth is achieved and the favorable outcome is superior to the protocol adopting vitrified ET cycle in our own setting. Additional studies are needed to verify this pilot data and validate its application in large randomized trials. PMID- 27006693 TI - Patients with mosaic methylation patterns of the Prader-Willi/Angelman Syndrome critical region exhibit AS-like phenotypes with some PWS features. AB - BACKGROUND: Loss of expression of imprinted genes in the 15q11.2-q13 region is known to cause either Prader-Willi syndrome (PWS) or Angelman syndrome (AS), depending on the parent of origin. In some patients (1 % in PWS and 2-4 % in AS), the disease is due to aberrant imprinting or gene silencing, or both. RESULTS: We report here a 4-year-old boy on whom a chromosomal microarray (CMA) was performed due to mild hand tremors, mild developmental delays, and clumsiness. CMA revealed absence of heterozygosity (AOH) spanning the entire chromosome 15, suggesting uniparental isodisomy 15. The patient had no definitive phenotypic features of PWS or AS. Methylation-sensitive multiplex ligation-dependent probe amplification (MS-MLPA) was performed to determine the parent of origin of the uniparental disomy (UPD) by examining methylation status at maternally imprinted sites. Interestingly, our patient had a mosaic methylation pattern. We identified nine additional previously tested patients with a similar mosaic methylation pattern. CMA was performed on these individuals retrospectively to test whether patients with mosaic methylation are more likely to have UPD of chromosome 15. Of the nine patients, only one had regions of AOH on chromosome 15; however, this patient had numerous regions of AOH on multiple chromosomes suggestive of consanguinity. CONCLUSION: The patients with mosaic methylation had milder or atypical features of AS, and the majority also had some features characteristic of PWS. We suggest that quantitative methylation analysis be performed for cases of atypical PWS or AS. It is also important to follow up with methylation testing when whole chromosome isodisomy is detected. PMID- 27006694 TI - A Gossypium BAC clone contains key repeat components distinguishing sub-genome of allotetraploidy cottons. AB - BACKGROUND: Dissecting genome organization is indispensable for further functional and applied studies. As genome sequences data shown, cotton genomes contain more than 60 % repetitive sequences, so study on repetitive sequences composition, structure, and distribution is the key step to dissect cotton genome. RESULTS: In this study, a bacterial artificial chromosome (BAC) clone enriched in repetitive sequences, was discovered initiatively by fluorescence in situ hybridization (FISH). FISHing with allotetraploidy cotton as target DNA, dispersed signals on most regions of all A sub-genome chromosomes, and only middle regions of all D sub-genome chromosomes were detected. Further FISHing with other cotton species bearing A or D genome as target DNA, specific signals were viewed. After BAC sequencing and bioinformational analysis, 129 repeat elements, size about 57,172 bp were found, accounting for more than 62 % of the BAC sequence (91,238 bp). Among them, a type of long terminal repeat retrotransposon (LTR-RT), LTR/Gypsy was the key element causing the specific FISH results. Using the fragments of BAC matching with the identified Gypsy-like LTR as probes, the BAC-57I23-like FISH signals were reappeared. Running BLASTN, the fragments had good match with all chromosomes of G. arboreum (A2) genome and A sub-genome of G. hirsutum (AD1), and had relatively inferior match with all chromosomes of D sub-genome of AD1, but had little match with the chromosomes of G. raimondii (D5) genome, which was consistent with the FISH results. CONCLUSION: A repeats-enriched cytogenetic marker to identify A and D sub-genomes of Gossypium was discovered by FISH. Combined sequences analysis with FISH verification, the assembly quality of repetitive sequences in the allotetraploidy cotton draft genome was assessed, and better chromosome belonging was verified. We also found the genomic distribution of the identified Gypsy-LTR-RT was similar to the distribution of heterochromatin. The expansion of this type of Gypsy-LTR RT in heterochromatic regions may be one of the major reasons for the size gap between A and D genome. The findings showed here will help to understand the composition, structure, and evolution of cotton genome, and contribute to the further perfection of the draft genomes of cotton. PMID- 27006695 TI - Outcome and periprocedural time management in referred versus directly admitted stroke patients treated with thrombectomy. AB - BACKGROUND: After thrombectomy has shown to be effective in acute stroke patients with large vessel occlusion, the potential benefit of secondary referral for such an intervention needs to be validated. AIMS: We aimed to compare consecutive stoke patients directly admitted and treated with thrombectomy at a neurointerventional centre with patients secondarily referred for such a procedure from hospitals with a stroke unit. METHODS: Periprocedure times and mortality in 300 patients primarily treated in eight neurointerventional centres were compared with 343 patients referred from nine other hospitals in a prospective multicentre study of a German neurovascular network. Data on functional outcome at 3 months was available in 430 (76.4%) patients. RESULTS: In hospital mortality (14.8% versus 11.7%, p = 0.26) and 3 months mortality (21.9% versus 24.1%, p = 0.53) were not statistically different in both patient groups despite a significant shorter symptom to groin puncture time in directly admitted patients, which was mainly caused by a longer interfacility transfer time. We found a nonsignificant trend for better functional outcome at 3 months in directly admitted patients (modified Rankin Scale 0-2, 44.0% versus 35.7%, p = 0.08). CONCLUSIONS: Our results show that a drip-and-ship thrombectomy concept can be effectively organized in a metropolitan stroke network. Every effort should be made to speed up the emergency interfacility transfer to a neurointerventional centre in stroke patients eligible for thrombectomy after initial brain imaging. PMID- 27006696 TI - Nontraumatic spinal cord injury at the neurological intensive care unit: spectrum, causes of admission and predictors of mortality. AB - OBJECTIVE: Nontraumatic spinal cord injuries (NTSCIs) form a heterogeneous group of diseases, which may evolve into a life-threatening condition. We sought to characterize spectrum, causes of admission and predictors of death in patients with NTSCI treated at the neurological intensive care unit (NICU). METHODS: We performed a retrospective observational analysis of NTSCI cases treated at a tertiary care center between 2001 and 2013. Among the 3937 NICU admissions were 93 patients with NTSCI (2.4%). Using multivariate logistic regression analysis, we examined predictors of mortality including demographics, etiology, reasons for admission and GCS/SAPS (Glasgow Coma Scale/Simplified Acute Physiology Score) scores. RESULTS: Infectious and inflammatory/autoimmune causes made up 50% of the NTSCI cases. The most common reasons for NICU admission were rapidly progressing paresis (49.5%) and abundance of respiratory insufficiency (26.9%). The mortality rate was 22.6% and 2.5-fold higher than in the cohort of all other patients treated at the NICU. Respiratory insufficiency as the reason for NICU admission [odds ratio (OR) 4.97, 95% confidence interval (CI) 1.38-17.9; p < 0.01], high initial SAPS scores (OR 1.04; 95% CI 1.003-1.08; p = 0.04), and the development of acute kidney injury throughout the stay (OR 7.25, 1.9-27.5; p = 0.004) were independent risk factors for NICU death. CONCLUSIONS: Patients with NTSCI account for a subset of patients admitted to the NICU and are at risk for adverse outcome. A better understanding of predisposing conditions and further knowledge of management of critically ill patients with NTSCI is mandatory. PMID- 27006697 TI - A discrete-choice experiment to determine patient preferences for injectable multiple sclerosis treatments in Germany. AB - OBJECTIVES: The aim of this study was to assess the relative importance of features of a hypothetical injectable disease-modifying treatment for patients with multiple sclerosis using a discrete-choice experiment. METHODS: German residents at least 18 years of age with a self-reported physician diagnosis of multiple sclerosis completed a 25-30 minute online discrete-choice experiment. Patients were asked to choose one of two hypothetical injectable treatments for multiple sclerosis, defined by different levels of six attributes (disability progression, the number of relapses in the next 4 years, injection time, frequency of injections, presence of flu-like symptoms, and presence of injection site reactions). The data were analyzed using a random-parameters logit model. RESULTS: Of 202 adults who completed the survey, results from 189 were used in the analysis. Approximately 50% of all patients reported a diagnosis of relapsing remitting multiple sclerosis, and 31% reported secondary progressive multiple sclerosis. Approximately 71% of patients had current or prior experience with injectable multiple sclerosis medication. Approximately 53% had experienced flu like symptoms caused by their medication, and 47% had experienced mild injection site reactions. At least one significant difference was seen between levels in all attributes, except injection time. The greatest change in relative importance between levels of an attribute was years until symptoms get worse from 1 to 4 years. The magnitude of this difference was about twice that of relapses in the next 4 years, frequency of injections, and flu-like symptoms. CONCLUSIONS: Most attributes examined in this experiment had an influence on patient preference. Patients placed a significant value on improvements in the frequency of dosing and disability progression. Results suggest that changes in injection frequency can be as important as changes in efficacy and safety attributes. Understanding which attributes of injectable therapies influence patient preference could potentially improve outcomes and adherence in patients with multiple sclerosis. PMID- 27006698 TI - Fludarabine add-on therapy in interferon-beta-treated patients with multiple sclerosis experiencing breakthrough disease. AB - BACKGROUND: Patients with relapsing-remitting multiple sclerosis (RRMS) may experience breakthrough disease despite effective interferon beta (IFNbeta) therapy. Fludarabine (FLU) is a chemotherapeutic agent used in lymphoproliferative disorders that may be synergistic when combined with immunomodulatory therapy to control active multiple sclerosis (MS). OBJECTIVE: The objective of this study was to explore the safety and tolerability of FLU versus monthly methylprednisolone (MP) in IFNbeta-treated RRMS patients with breakthrough disease. Clinical and MRI effects of IFNbeta-1a plus FLU were evaluated. METHODS: Eighteen patients with breakthrough disease [?2 relapses over the prior year and ?1.0-point increase in Expanded Disability Status Scale (EDSS) score sustained for ?3 months] after >1 year of IFNbeta therapy were enrolled in this prospective, open-label, randomized, proof-of-concept, pilot study. Patients received intravenous (IV) MP 1 g daily for 3 days and then were randomized to receive 3 monthly IV infusions of FLU 25 mg/m(2) daily for 5 consecutive days (n = 10) or MP 1 g (n = 8). All patients maintained their intramuscular IFNbeta-1a treatment throughout the study. Analyses explored safety signals and directional trends; this preliminary study was not powered to detect clinically meaningful differences. RESULTS: Both combination treatments were safe and well tolerated, with all adverse events mild. Patients treated with IFNbeta-1a plus FLU had similar relapse rates, EDSS scores, and MS Functional Composite scores, but significantly less acute corticosteroid use for on-study relapses and better responses on some MRI outcomes, versus patients treated with IFNbeta-1a plus MP. CONCLUSIONS: Further study of FLU for breakthrough disease in patients with RRMS is warranted. PMID- 27006699 TI - Management of epilepsy during pregnancy: an update. AB - The clinical management of women with epilepsy on antiepileptic drugs (AEDs) during pregnancy presents unique challenges. The goal of treatment is optimal seizure control with minimal in utero fetal exposure to AEDs in an effort to reduce the risk of structural and neurodevelopmental teratogenic effects. This paper reviews the following key issues pertaining to women with epilepsy during pregnancy: AED pharmacokinetics; clinical management of AEDs; seizure frequency; major congenital malformation; neurodevelopmental outcomes; perinatal complications; and breast feeding. PMID- 27006700 TI - Fingolimod in the treatment of relapsing-remitting multiple sclerosis: long-term experience and an update on the clinical evidence. AB - Since the approval in 2010 of fingolimod 0.5 mg (Gilenya; Novartis Pharma AG, Basel, Switzerland) in the USA as an oral therapy for relapsing forms of multiple sclerosis, long-term clinical experience with this therapy has been increasing. This review provides a summary of the cumulative dataset from clinical trials and their extensions, plus postmarketing studies that contribute to characterizing the efficacy and safety profile of fingolimod in patients with relapsing forms of multiple sclerosis. Data from the controlled, phase III, pivotal studies [FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis), FREEDOMS II and TRANSFORMS (Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis)] in relapsing remitting multiple sclerosis have shown that fingolimod has a robust effect on clinical and magnetic resonance imaging outcomes. The respective study extensions show that effects on annualized relapse rates are sustained with continued fingolimod treatment. Consistent, significant reductions in magnetic resonance imaging lesion counts and brain volume loss have also been sustained with long term treatment. The safety profile of fingolimod is also examined, particularly in light of its long-term use. A summary of the adverse events of interest that are associated with fingolimod treatment and associated label guidelines are also considered, which include cardiac effects following first-dose administration, infections, lymphopenia, macular edema and pregnancy. Historic hurdles to the prescription of fingolimod and how these challenges are being met are also discussed. PMID- 27006701 TI - Application of recombinant TAF3 PHD domain instead of anti-H3K4me3 antibody. AB - BACKGROUND: Histone posttranslational modifications (PTMs) represent a focal point of chromatin regulation. The genome-wide and locus-specific distribution and the presence of distinct histone PTMs is most commonly examined with the application of histone PTM-specific antibodies. In spite of their central role in chromatin research, polyclonal antibodies suffer from disadvantages like batch-to batch variability and insufficient documentation of their quality and specificity. RESULTS: To mitigate some of the pitfalls of using polyclonal antibodies against H3K4me3, we successfully validated the application of a recombinant TAF3 PHD domain as anti-H3K4me3 affinity reagent in peptide array, western blot and ChIP-like experiments coupled with qPCR and deep sequencing. CONCLUSIONS: The successful addition of the TAF3 PHD domain to the growing catalog of recombinant affinity reagents for histone PTMs could help to improve the reproducibility, interpretation and cross-laboratory validation of chromatin data. PMID- 27006702 TI - Patterns of foot complaints in systemic lupus erythematosus: a cross sectional survey. AB - BACKGROUND: Foot complaints are common in inflammatory arthropathies such as rheumatoid arthritis and cause considerable disability. However, little is published about the nature and extent of foot complaints in systemic lupus erythematosus (SLE). We aimed to explore foot complaints among people with (SLE) and to evaluate the associations between foot pain and self-reported activities of daily living and well-being. METHODS: We developed and tested a new 40-item item self-administered questionnaire, using a five-stage development process utilising patient involvement throughout to ensure face and content validity. The self-administered instrument was posted to 406 people with SLE attending adult rheumatology clinics across three health boards in Auckland, New Zealand. The questionnaire enquired about symptoms of foot pain, extra-articular features, anatomical distribution of symptoms according to validated foot-mannequins and the impact of foot symptoms on activities of daily living and well-being. RESULTS: In total, 406 questionnaires were posted, with 131 responses (response rate 32 %). We found 89 % were women, mean (SD) age 51 (15) years, mean (SD) diagnosis 12.5 (11.1) years. Overall, 77 % of those responding to the questionnaire reported foot pain during their SLE, with 45 % reporting current foot pain. All regions of the feet were affected, with the hindfoot (32 %) and ankles (30 %) most troublesome. The most common self-reported extra-articular foot complaints were cold feet, swelling and numbness. Almost two-thirds (61 %) reported foot pain adversely affected their lives; foot pain prevented sleeping in 36 % and had a negative effect on emotions for 33 %. Only 33 % of participants had seen a podiatrist. Significant association was found between foot pain and standing longer than 15 min (p < 0.001), walking (p < 0.001), climbing stairs (p < 0.001) and going shopping (p < 0.001). Pain was the primary symptom to affect quality of life (47/100). CONCLUSION: Foot complaints in SLE are heterogeneous in nature, and may have a substantial negative impact on patient well-being. Foot complaints need to be addressed to reduce the burden of SLE and our findings support the need for wider access to specific foot care services. PMID- 27006703 TI - 'Trial and error...', '...happy patients' and '...an old toy in the cupboard': a qualitative investigation of factors that influence practitioners in their prescription of foot orthoses. AB - BACKGROUND: Foot orthoses are used to manage of a plethora of lower limb conditions. However, whilst the theoretical foundations might be relatively consistent, actual practices and therefore the experience of patients is likely to be less so. The factors that affect the prescription decisions that practitioners make about individual patients is unknown and hence the way in which clinical experience interacts with knowledge from training is not understood. Further, other influences on orthotic practice may include the adoption (or not) of technology. Hence the aim of this study was to explore, for the first time, the influences on orthotic practice. METHODS: A qualitative approach was adopted utilising two focus groups (16 consenting participants in total; 15 podiatrists and 1 orthotist) in order to collect the data. An opening question "What factors influence your orthotic practice?" was followed with trigger questions, which were used to maintain focus. The dialogue was recorded digitally, transcribed verbatim and a thematic framework was used to analyse the data. RESULTS: There were five themes: (i) influences on current practice, (ii) components of current practice, (iii) barriers to technology being used in clinical practice, (iv) how technology could enhance foot orthoses prescription and measurement of outcomes, and (v) how technology could provide information for practitioners and patients. A final global theme was agreed by the researchers and the participants: 'Current orthotic practice is variable and does not embrace technology as it is perceived as being not fit for purpose in the clinical environment. However, practitioners do have a desire for technology that is usable and enhances patient focussed assessment, the interventions, the clinical outcomes and the patient's engagement throughout these processes'. CONCLUSIONS: In relation to prescribing foot orthoses, practice varies considerably due to multiple influences. Measurement of outcomes from orthotic practice is a priority but there are no current norms for achieving this. There have been attempts by practitioners to integrate technology into their practice, but with largely negative experiences. The process of technology development needs to improve and have a more practice, rather than technology focus. PMID- 27006704 TI - The isolation and molecular characterization of Mycobacterium avium subsp. paratuberculosis in Shandong province, China. AB - BACKGROUND: Mycobacterium avium subspecies paratuberculosis (Map) causes Johne's disease in domestic and wild ruminants. It has been a debate that whether Map can cause Crohn's disease in human. To our knowledge there is no report about molecular characterization of Map in China, although several Map strains have been reported in other country. The objectives of this study was to know the recent prevalence of Johne's disease in dairy farms in Shandong province, and have a better understanding of genotypic distribution of Map in China. METHODS: Johne's disease was detected from 1038 individuals in 19 dairy farms by ELISA. Map in fecal and milk specimens was identified by Ziehl-Neelsen staining and confirmed using PCR-REA. In addition, frozen sections of ileum and mesenteric lymph nodes from two Map shedding cows were performed to observe the histopathological changes. Next-generation sequencing technology was performed to get whole genome sequences. RESULT: A total of 121 (11.7 %) animals were positive for Map antibody from 1038 sera tested, and 11 (57.9 %) dairy herds were positive for Map antibody. Typically histopathologic changes were observed in mesenteric lymph nodes. We have successfully isolated two Map strains, which both were Map C. The current genome-wide analysis showed that the genome size of our isolates are respectively 4,750,273 and 4,727,050 bp with a same G + C content of 69.3 %, and the numbers of single nucleotide polymorphisms (SNPs) against Map K-10 are respectively 292 and 296. CONCLUSION: Map is a prevalent pathogen among dairy cattle in China. This study successfully isolated two Map strains from one Chinese dairy herd with signs of diarrhoea, and identified that the two isolates were both Map-C. Furthermore, these isolates were most closely related to Map K 10. PMID- 27006705 TI - Helicobacter pylori plasticity region genes are associated with the gastroduodenal diseases manifestation in India. AB - BACKGROUND: Almost all Helicobacter pylori infected person develop gastritis and severe gastritis is supposed to be the denominator of peptic ulcer diseases, which may lead to gastric cancer. However, it is still an enigma why few strains are associated with ulcer formation, while others are not related with any disease outcome. Although a number of putative virulence factors have been reported for H. pylori, there are contradictory results regarding their connotation with diseases. Recently, there has been a significant attention in strain-specific genes outside the cag pathogenicity island, especially genes within plasticity regions. Studies demonstrated that certain genes in this region may play important roles in the pathogenesis of H. pylori-associated diseases. The aim of this study was to assess the role of selected genes (jhp0940, jhp0945, jhp0947 and jhp0949) in the plasticity region in relation to risk of H. pylori related diseases in Indian population. METHODS: A total of 113 H. pylori strains isolated from duodenal ulcer (DU) (n = 61) and non-ulcer dyspepsia (NUD) subjects (n = 52) were screened by PCR and Dot-Blot to determine the presence of these genes. The comparative study of IL-8 production and apoptosis were also done by co-culturing the AGS cells with H. pylori strains of different genotype. RESULTS: PCR and Dot-Blot results indicated that the prevalence rates of jhp0940, jhp0945, jhp0947 and jhp0949 in the H. pylori strains were 9.8, 47.5, 50.8, 40.9 % and 17.3, 28.8, 26.9, 19.2 % isolated from DU and NUD, respectively. IL-8 production and apoptotic cell death were significantly higher in H. pylori strains containing jhp0945, jhp0947 and jhp0949 than the strains lacking those genes. Results indicated that the prevalence of jhp0945, jhp0947 and jhp0949 are associated with increased risk of severe diseases in India. CONCLUSION: Our study showed that presence of jhp0945, jhp0947 and jhp0949 were significantly associated with symptomatic expressions along with the increased virulence during in vitro study whereas jhp0940 seems to be negatively associated with the disease. These results suggest that jhp0945, jhp0947 and jhp0949 could be useful prognostic markers for the development of duodenal ulcer in India. PMID- 27006706 TI - Dipeptidyl peptidase-4 inhibitors improve arterial stiffness, blood pressure, lipid profile and inflammation parameters in patients with type 2 diabetes mellitus. AB - BACKGROUND: This uncontrolled open label study evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i): sitagliptin and vildagliptin on augmentation index standardized for 75 beats per minute (cAiX@75), blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) in patients with type 2 diabetes mellitus (T2DM). METHODS: Fifty-one well-regulated T2DM patients were randomly assigned to either sitagliptin or vildagliptin (100 mg/day) for 3 months continuing their previous treatment. Lipid profile, cAiX@75, hsCRP, glycated hemoglobin (HbA1c) were measured at baseline at 4, 8 and 12th week were accessed. cAiX@75 and pulse wave velocity (PWV) were determined by SphygmoCor device. RESULTS: Following DPP-4 treatment there was a significant reduction in total serum cholesterol (5.18 vs 4.62 mmol/L), low-density lipoprotein (2.89 vs 2.54 mmol/L), hsCRP (3.21 vs 1.95 mg/L), cAiX@75 (24.5 vs 22.3) and central systolic BP (131.8 vs 119.5 mmHg). The sitagliptin treated group reached cAiX@75 reduction earlier in the study period while neither sitagliptin or vildagliptin use resulted in the significant HbA1c reduction. CONCLUSION: The treatment with DPP 4i: sitagliptin and vildagliptin provides favorable metabolic and vascular effects beyond glucose-control. Further studies are required to elucidate their implication in metabolic pathways. PMID- 27006707 TI - Prevalence of metabolic syndrome in non-diabetic, pregnant Angolan women according to four diagnostic criteria and its effects on adverse perinatal outcomes. AB - BACKGROUND: Metabolic syndrome (MetS) is a cluster of risk factors for type 2 diabetes (Type2 DM) and cardiovascular diseases (CVD), and its prevalence varies based on region, population, and sex. Newborns of women with MetS have a greater risk of adverse perinatal outcomes. This study explores the prevalence of metabolic syndrome in non-diabetic, pregnant Angolan women and the adverse perinatal outcomes associated with it. METHODS: This cross-sectional study collected the demographic, anthropometric and clinical data of 675 pregnant women in the maternity ward of General Hospital in Huambo, Angola. Metabolic syndrome was defined using four criteria: the third report of the National Cholesterol Education Program Adult Treatment Panel (ATPIII), the Joint Interim Statement (JIS), and definitions by both Bartha et al. and Chatzi et al. RESULTS: The crude prevalence of metabolic syndrome was 36.6 % based on the JIS definition, 29.2 % based on NCEP ATPIII, 12.6 % based on Chatzi et al. and 1.8 % based on Bartha et al. In general, the prevalence of adverse perinatal outcomes was 14.1 %. CONCLUSIONS: There was a high prevalence of metabolic syndrome, depending on the criteria used, and thus a great need to harmonize the criteria and cutoff points. Perinatal adverse outcomes were higher in pregnant women with metabolic syndrome. PMID- 27006708 TI - Considering Rotatability of Hydroxyl Groups for the Active Site Residues of MMP 13 in Retrospective Virtual Screening Campaigns. AB - Considering different orientation of hydroxyl and thiol groups of receptor residues such as Thr, Tyr, Ser and Cys is an option available on Glide docking software. This is an attempt that can provide more realistic ligand-receptor interactions. Matrix metalloproteinase 13 (MMP-13) is a suggested target for several diseases including osteoarthritis and cancer. MMP-13 was selected as a receptor with reported flexibility in the active site residues. Four residues in the MMP-13 active site were selected and their hydroxyl groups were made flexible during docking: Tyr(241), Thr(242), Tyr(243) and Thr(244). The ability of retrospective virtual screenings using a rigid receptor for discriminating between actives and decoys were compared to those using receptor with different combination of flexible residues. Statistical analysis of the results and inspecting the binding pose of the ligands suggested that the hydroxyl orientation of Tyr(241), Thr(242), Tyr(243) and Thr(244) (in particular Thr(242) and to a lesser extent Thr(244)) had impacts on the MMP-13 docking results. PMID- 27006709 TI - Oxidative Damage in the Aging Heart: an Experimental Rat Model. AB - INTRODUCTION: Several theories have been proposed to explain the cause of 'aging'; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. METHODS: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. RESULTS: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. CONCLUSION: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID- 27006710 TI - Impact of Magnesium L-Lactate on Occurrence of Ventricular Arrhythmias in Patients with Implantable Cardioverter Defibrillators: A Randomized, Placebo Controlled Trial. AB - BACKGROUND: We evaluated the antiarrhythmic efficacy and quality of life (QoL) impact of oral magnesium Llactate on patients with an implantable cardioverter defibrillator (ICD). METHODS: This prospective, double-blind, placebo-controlled trial randomized 70 patients with an ICD to receive oral magnesium L-lactate 3 tablets twice daily (504mg elemental magnesium daily) or matching placebo for 12 months. Patients were seen at baseline, 12, 24, 36, and 52 weeks. The primary endpoints were the cumulative occurrence of ICD therapy [either shock or anti tachycardia pacing (ATP)] or QoL between the groups. RESULTS: Among the 70 randomized patients with a mean +/- SD follow-up of 6.4 +/- 4.1 months, 10 patients in the placebo group and 8 in the magnesium group experienced either ICD shock or ATP [HR 0.84, 95% CI 0.33 to 2.12; p=0.706]. Without significant arrhythmia suppression, only minimal effects on QoL were seen. Eighty six percent of all patients had serum intracellular magnesium deficiency. CONCLUSION: In our underpowered trial, patients with ICDs had intracellular magnesium deficiency but oral magnesium Llactate only nonsignificantly reduced the occurrence of ICD therapies and had little impact on HrQoL. PMID- 27006711 TI - Imaging Aortic Regurgitation: The Incremental Benefit of Speckle Tracking Echocardiography. AB - Aortic regurgitation (AR) affects global left ventricular mechanics. However, limited literature is available on how it may affect regional longitudinal strain. We present a case where severe AR jet is thrashing the anterior-septal wall and reducing its overall longitudinal performance most likely secondary to increased wall shear stress in diastole. This new insight into patho physiological process using deformation study may have supplementary impact in decision making for surgical intervention. Transthoracic echocardiography is the primary imaging modality for the assessment of AR as it offers evaluation of severity of AR, aetiology of AR, left ventricular (LV) dilatation, LV systolic function, left ventricular mass, diastolic function and global strain. This case highlights the regional disturbances in longitudinal strain in eccentric AR. PMID- 27006712 TI - Outcomes of Primary Percutaneous Coronary Intervention for Patients with Previous Coronary Artery Bypass Grafting Presenting with STsegment Elevation Myocardial Infarction. AB - BACKGROUND: There are limited data on outcomes of patients with previous coronary artery bypass grafting (CABG) presenting acutely as ST-segment elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PPCI). OBJECTIVES: To compare outcomes in STEMI patients undergoing PPCI with or without previous CABG surgery. METHODS: An all-comer single-centre observational registry from a cardiothoracic centre in UK. All consecutive patients presenting for PPCI between 2007 and 2012 were included. Electronic records were used to extract relevant information. Mortality data were obtained from the Office of National Statistics. Overall median follow-up period was 1.7 years (intraquartile range 0.9-2.5). RESULTS: Complete data were available for 2133 (97%) patients. 47-patients had previous history of CABG. Out of these, the infarct related artery (IRA) was native vessel in 22 and graft in 25 patients. Post re-vascularization TIMI flow was inferior in CABG cohort (50 mm]. The initial dose of IN ketamine was 0.7 mg/kg with an additional dose of 0.3 mg/kg if VAS was more than 50 mm after 15 minutes. Pain scores and vital signs were recorded at 0, 15, 30 and 60 minutes. Side-effects, sedation level and patient's satisfaction were also recorded. The primary outcome was the number of patients achieving >= 20 mm reductions in VAS at 15 minutes. Other secondary outcome measures were median reduction in VAS at 15, 30 and 60 minutes, changes of vital signs, adverse events, satisfaction of patients, and need for additional ketamine. RESULTS: Thirty-four patients with a median age of 29.5 years (IQR 17.5-38) were enrolled, and they had an initial median VAS of 80 mm (IQR 67-90). The VAS decreased more than 20 mm at 15 minutes in 27 (80%) patients. The reduction of VAS from baseline to 40 mm (IQR 20-40), 20 mm (IQR 14 20) and 20 mm (IQR 10-20) respectively at 15, 30 and 60 minutes (P<0.001). No critical changes of vital signs were noted and adverse effects were mild and transient. CONCLUSION: This study showed that IN ketamine is an analgesic choice for patients with acute injury in moderate to severe pain in an overcrowded and resource limited ED. PMID- 27006734 TI - Analgesic effect of paracetamol combined with low-dose morphine versus morphine alone on patients with biliary colic: a double blind, randomized controlled trial. AB - BACKGROUND: Numerous drugs have been proposed to alleviate pain in patients with biliary colic, especially opioids, but still there is a tendency to use less narcotics because of their side effects and the unwillingness of some patients. The present study aimed to compare the analgesic effect of paracetamol combined with low-dose morphine versus morphine alone in patients with biliary colic. METHODS: A randomized double-blind controlled trial was performed in 98 patients with biliary colic, recruited from two emergency departments from August 2012 to August 2013. Eleven patients were excluded and the remaining were randomized into two groups: group A received 0.05 mg/kg morphine+1 000 mg paracetamol in 100 mL normal saline and group B received 0.1 mg/kg morphine+normal saline (100 mL) as placebo. Pain scores were recorded using visual analogue scale (VAS) at baseline and 15 and 30 minutes after drug administration. Adverse effects and the need for rescue medication (0.75 ug/kg intravenous fentanyl) were also reported within 60 minutes of drug administration. RESULTS: Before the infusion, the mean+/-SD VAS scores were 8.73+/-1.57 in group A and 8.53+/-1.99 in group B. At 15 minutes after drug administration, the mean+/-SD VAS scores were 2.16+/-1.90 in group A vs. 2.51+/-1.86 in group B; mean difference was -0.35, and 95%CI -1.15 to 0.45 (P=0.38). At 30 minutes the mean+/-SD VAS scores were 1.66+/-1.59 in group A vs. 2.14+/-1.79 in group B; mean difference was -0.48, and 95%CI -1.20 to 0.24 (P=0.19). The mean pain scores in the two groups at 15 and 30 minutes demonstrated no significant difference. CONCLUSION: Paracetamol combined with low dose morphine may be effective for pain management in patients with biliary colic. PMID- 27006735 TI - Comparison of intravenous pantoprazole and ranitidine in patients with dyspepsia presented to the emergency department: a randomized, double blind, controlled trial. AB - BACKGROUND: This study aimed to compare pantoprazole, a proton-pomp inhibitors (PPIs), and ranitidine, a H2 receptor antagonists (H2RA), in ceasing dyspeptic symptoms in the emergency department (ED). METHODS: This randomized, double blinded study compared the effectiveness of 50 mg ranitidine (Ulcuran((r))) and 40 mg pantoprazole (Pantpas((r))), given in a 100 mL saline solution by an intravenous rapid infusion within 2-4 minutes in patients with dyspepsia presented to the ED. Pain intensity was measured at baseline, 30 and 60 minutes after the drug administration. RESULTS: A total of 72 patients were eligible for the study. Of these patients, 2 were excluded from the study because the initial visual analogue scale (VAS) scores were under 20 mm and 4 were excluded from the statistical analysis because of being diagnosed as having other causes of epigastric pain despite being allocated to one of the study groups. Thirty-three patients in the pantoprazole group and 33 patients in the ranitidine group were analyzed ultimately. The mean age of the patients was 36.6+/-15 years, and 26 (39.4%) patients were male. Both of the groups reduced pain effectively at 30 [27.6+/-28 (18 to 37) vs. 28.3+/-23 (20 to 37), respectively] and 60 minutes [39.6+/-39 (26 to 53) vs. 42.3+/-25 (33 to 51), respectively]. There were 13 (39.4%) patients in the pantoprazole group and 8 (24.2%) patients in the ranitidine group who required additional drug at the end of the study (P=0.186). CONCLUSION: Intravenous pantoprazole and ranitidine are not superior to each other in ceasing dyspeptic symptoms at 30 and 60 minutes in the ED. PMID- 27006736 TI - Emergency department patients with small bowel obstruction: What is the anticipated clinical course? AB - BACKGROUND: Emergency physicians (EPs) often care for patients with acute small bowel obstruction. While some patients require exploratory laparotomy, others are managed successfully with supportive care. We aimed to determine features that predict the need for operative management in emergency department (ED) patients with small bowel obstruction (SBO). METHODS: We performed a retrospective chart review of 370 consecutive patients admitted to a large urban academic teaching hospital with a diagnosis of SBO over a two-year period. We evaluated demographic characters (prior SBO, prior abdominal surgery, active malignancy) and clinical findings (leukocytosis and lactic acid) to determine features associated with the need for urgent operative intervention. RESULTS: Patients with a prior SBO were less likely to undergo operative intervention [20.3% (42/207)] compared to those without a prior SBO [35.2% (57/162)]. Abnormal bloodwork was not associated with need for operative intervention. 68% of patients with CT scan findings of both an SBO and a hernia, however, were operatively managed. CONCLUSIONS: Patients with a history of SBO were less likely to require operative intervention at any point during their hospitalization. Abnormal bloodwork was not associated with operative intervention. The CT finding of a hernia, however, predicted the need for operative intervention, while other findings (ascites, duodenal thickening) did not. Further research would be helpful to construct a prediction rule, which could help community EPs determine which patients may benefit from expedited transfer for operative management, and which patients could be safely managed conservatively as an initial treatment strategy. PMID- 27006737 TI - A correlation analysis of BroselowTM Pediatric Emergency Tape-determined pediatric weight with actual pediatric weight in India. AB - BACKGROUND: The BroselowTM Pediatric Emergency Tape indicates standardized, pre calculated medication doses, dose delivery volumes, and equipment sizes using color-coded zones based on height-weight correlations. The present study attempted to provide more evidence on the effectiveness of the BroselowTM Pediatric Emergency Tape by comparing the tape-estimated weights with actual weights. We hypothesized that the BroselowTM Pediatric Emergency Tape would overestimate weights in Indian children aged<10 years, leading to inaccurate dosing and equipment sizing in the emergency setting. METHODS: This prospective study of pediatric patients aged <10 years who were divided into three groups based on actual body weight: <10 kg, 10-18 kg, and >18 kg. We calculated the percentage difference between the Broselow-predicted weight and the measured weight as a measure of tape bias. Concordant results were those with a mean percent difference within 3%. Standard deviation was measured to determine precision. Accuracy was determined as color-coded zone prediction and measured weight concordance, including the percentage overestimation by 1-2 zones. RESULTS: The male-to-female ratio of the patients was 1.3:1. Total agreement between color-coding was 63.18% (kappa=0.582). The BroselowTM color-coded zone agreement was 74.8% in the <10 kg group, 61.24% in the 10-18 kg group, and 53.42% in the >18 kg group. CONCLUSIONS: The BroselowTM Pediatric Emergency Tape showed good evidence for being more reliable in children of the <10 kg and 10-18 kg groups. However, as pediatric weight increased, predictive reliability decreased. This raises concerns over the use of the BroselowTM Pediatric Emergency Tape in Indian children because body weight was overestimated in those weighing >18 kg. PMID- 27006738 TI - Assessment of a predictive score for pulmonary complications in cancer patients after esophagectomy. AB - BACKGROUND: Esophagectomy is a very important method for the treatment of resectable esophageal cancer, which carries a high rate of morbidity and mortality. This study was undertaken to assess the predictive score proposed by Ferguson et al for pulmonary complications after esophagectomy for patients with cancer. METHODS: The data of patients who admitted to the intensive care unit after transthoracic esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College between September 2008 and October 2010 were retrospectively reviewed. RESULTS: Two hundred and seventeen patients were analyzed and 129 (59.4%) of them had postoperative pulmonary complications. Risk scores varied from 0 to 12 in all patients. The risk scores of patients with postoperative pulmonary complications were higher than those of patients without postoperative pulmonary complications (7.27+/-2.50 vs. 6.82+/ 2.67; P=0.203). There was no significant difference in the incidence of postoperative pulmonary complications as well as in the increase of risk scores (chi (2)=5.477, P=0.242). The area under the curve of predictive score was 0.539+/-0.040 (95%CI 0.461 to 0.618; P=0.324) in predicting the risk of pulmonary complications in patients after esophagectomy. CONCLUSION: In this study, the predictive power of the risk score proposed by Ferguson et al was poor in discriminating whether there were postoperative pulmonary complications after esophagectomy for cancer patients. PMID- 27006740 TI - Chest X-rays in detecting injuries caused by blunt trauma. AB - BACKGROUND: The appropriate sequence of different imagings and indications of thoracic computed tomography (TCT) in evaluating chest trauma have not yet been clarified at present. The current study was undertaken to determine the value of chest X-ray (CXR) in detecting chest injuries in patients with blunt trauma. METHODS: A total of 447 patients with blunt thoracic trauma who had been admitted to the emergency department (ED) in the period of 2009-2013 were retrospectively reviewed. The patients met inclusion criteria (age>8 years, blunt injury to the chest, hemodynamically stable, and neurologically intact) and underwent both TCT and upright CXR in the ED. Radiological imagings were re-interpreted after they were collected from the hospital database by two skilled radiologists. RESULTS: Of the 447 patients, 309 (69.1%) were male. The mean age of the 447 patients was 39.5+/-19.2 (range 9 and 87 years). 158 (35.3%) patients were injured in motor vehicle accidents (MVA). CXR showed the highest sensitivity in detecting clavicle fractures [95%CI 78.3 (63.6-89)] but the lowest in pneuomediastinum [95%CI 11.8 (1.5-36.4)]. The specificity of CXR was close to 100% in detecting a wide array of entities. CONCLUSION: CXR remains to be the first choice in hemodynamically unstable patients with blunt chest trauma. Moreover, stable patients with normal CXR are candidates who should undergo TCT if significant injury has not been ruled out. PMID- 27006739 TI - Periplaneta americana extract used in patients with systemic inflammatory response syndrome. AB - BACKGROUND: Periplaneta americana extract is recognized to have a positive effect on gastrointestinal mucosa. This study aimed to investigate the effects of periplaneta americana extract on immune function, nutrition status and gastrointestinal complications of early enteral nutrition patients with systemic inflammatory response syndrome (SIRS). METHODS: Patients with SIRS were randomly divided into two groups: treatment and control groups. All patients in the two groups received conventional therapy including enteral nutrition, but periplaneta americana extract, an additional Chinese medicine, was given to the patients in the treatment group. At the beginning of treatment (0 day) and 1, 3, and 7 days after treatment, the levels of immunoglobulin (IgA), total lymphocyte count (TLC), total protein (TP) and prealbumin (PA) were respectively tested in patients' venous blood. The incidences of bloating, diarrhea, aspiration pneumonia and high blood sugar at 7 days after treatment were recorded. The mortality of the patients in 28 days was recorded. RESULTS: At 3 and 7 days after treatment, the levels of IgA and TLC in the treatment group were higher than those in the control group (P<0.05). At 7 days after treatment, the levels of TP and PA in the treatment group were higher than those in the control group (P<0.05). The incidences of bloating and diarrhea in the treatment group were lower than those in the control group, the differences were significant (P<0.05). The mortality of treatment group was lower than that of the control group (P>0.05). CONCLUSION: Periplaneta americana extract could reduce gastrointestinal complications and improve immune function and nutritional status in patients with systemic inflammatory response syndrome. PMID- 27006741 TI - Critical care nurses' attitude towards life-sustaining treatments in South East Iran. AB - BACKGROUND: Life-sustaining treatments (LSTs) may prolong life but greatly decrease the quality of death. One factor influencing decision-making about withholding and withdrawing these treatments is the attitude of nurses. This study aimed to evaluate the attitude of critical care nurses towards life sustaining treatments in South East Iran. METHODS: In this cross-sectional study, "Ethnicity and Attitudes towards Advance Care Directives Questionnaire" was used to investigate the attitude of 104 critical care nurses towards life-sustaining treatments in three hospitals affiliated to Kerman University of Medical Sciences. RESULTS: The findings of this study indicated that although a majority of critical care nurses (77%) did not have personal desire for use of LSTs including CPR and mechanical ventilation, they had moderately negative to neutral attitude towards general use of LSTs (2.95 of 5). CONCLUSIONS: These findings suggest that nurses' attitude towards LSTs can be changed by inclusion of specific courses about death, palliative care and life-sustaining treatments in undergraduate and postgraduate nursing curricula. Educating Muslim nurses about religious aspects of LSTs may also improve their attitudes. PMID- 27006742 TI - The Chikungunya virus: An emerging US pathogen. AB - BACKGROUND: The Chikungunya (CHIK) virus was recently reported by the CDC to have spread to the United States. We report an early documented case of CHIK from the state of Pennsylvania after a patient recently returned from Haiti in June of 2014. METHODS: A 39-year-old man presented to the emergency department complaining of fever, fatigue, polyarthralgias and a diffuse rash for two days. Four days before, he returned from a mission trip to Haiti and reported that four of his accompanying friends had also become ill. A CHIK antibody titer was obtained and it was found to be positive. During his hospital stay, he responded well to supportive care, including anti-inflammatories, intravenous hydration and anti-emetics. RESULTS: His condition improved within two days and he was ultimately discharged home. CONCLUSIONS: Manifestations of CHIK can be similar to Dengue fever, which is transmitted by the same species of mosquito, and occasionally as a co-infection. Clinicians should include Chikungunya virus in their differential diagnosis of patients who present with fever, polyarthralgia and rash with a recent history of travel to endemic areas, including those within the United States. PMID- 27006743 TI - Invasive group B streptococcal infection in a patient with post splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension. AB - BACKGROUND: Splenectomy in patients with liver cirrhosis (LC) is expected to become more common owing to its efficacy on portal hemodynamics. In this report we describe an alarming case of group B streptococcus (GBS) infection after splenectomy in a patient with LC. METHODS: A 72-year-old woman with a history of LC was admitted to our emergency department because of respiratory failure. The patient had received left lateral segmentectomy of the liver and splenectomy three months before admission. Pulmonary examination revealed significant wheezing during inspiration and expiration, but no crackles and stridor. Chest radiography and CT showed no infiltrates. A presumptive diagnosis of bronchial asthma caused by upper respiratory infection was made. Four days after admission, GBS infection was confirmed by blood culture and penicillin G was administered. Antibiotics were given intravenously for a total of 12 days. RESULTS: The patient was discharged on the 12th day after admission. CONCLUSIONS: Although efficacy of splenectomy in patients with LC has been reported, immune status should be evaluated for a longer period. Patients who have undergone splenectomy are highly susceptible to bacteria; moreover, LC itself is an independent risk factor for mortality in patients with sepsis. Since prophylaxis against GBS has not been established, immediate action should be taken. Emergency physicians should be aware of invasive GBS infection in the context of the critical risk factors related to splenectomy and LC, particularly the expected increase of splenectomy performed in LC patients. PMID- 27006744 TI - Generalized seizure, the only manifestation of a small ischemic atherothrombotic infarction. AB - BACKGROUND: According to the literature, generalized seizure as a presenting sign of stroke is rare, and in the reported cases it was accompanied by a focal neurological deficit. Presentation of a small ischemic atherothrombotic brain infarction with convulsive generalized seizure is very rare. METHODS: We reported a patient with acute small ischemic atherothrombotic infarction associated with an episode of generalized tonic-clonic seizure, a rare clinical manifestation in this type of stroke. The patient was treated with anti-epileptic therapy after admission. RESULTS: The patient was discharged with oral administration of phenytoin 100 mg TDS, aspirin 80 mg daily, and atorvastatin 40 mg daily. CONCLUSION: Small ischemic atherothrombotic infarction can present only with a seizure without any focal neurological deficit. PMID- 27006745 TI - Ultrasound diagnosis of diverticulitis. PMID- 27006747 TI - Modulation of Oxidative Stress: Pharmaceutical and Pharmacological Aspects. PMID- 27006746 TI - Oxidative Stress in Atopic Dermatitis. AB - Atopic dermatitis (AD) is a chronic pruritic skin disorder affecting many people especially young children. It is a disease caused by the combination of genetic predisposition, immune dysregulation, and skin barrier defect. In recent years, emerging evidence suggests oxidative stress may play an important role in many skin diseases and skin aging, possibly including AD. In this review, we give an update on scientific progress linking oxidative stress to AD and discuss future treatment strategies for better disease control and improved quality of life for AD patients. PMID- 27006748 TI - Sociodemographic and Lifestyle Determinants of Plasma Oxidative Stress Markers 8 OHdG and F2-Isoprostanes and Associations with Metabolic Syndrome. AB - Background. Oxidative stress is increasingly important in health research. Therefore, it is necessary to understand which factors determine basal oxidative stress. This study examines the associations of various determinants with markers of oxidative DNA and lipid damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG) and F2 isoprostanes. Methods. Data are from the Netherlands Study of Depression and Anxiety; 1117 subjects (18-65 years) without a current psychiatric diagnosis. Multivariable regression analyses were conducted with plasma levels of 8-OHdG and F2-isoprostanes (measured by LC/MS-MS) including sociodemographic, lifestyle, and sampling variables. Associations with metabolic syndrome (MetS) and chronic disease were examined. Results. 8-OHdG and F2-isoprostanes were weakly correlated (r = 0.06, p = 0.045). Both were positively associated with age and cotinine (cigarette exposure); 8-OHdG was lower in females and after longer sample storage. F2-isoprostanes were higher in females, alcohol users, and in samples collected in spring and lower in supplement users and those with more education. Both markers were lower in fasting subjects. F2-isoprostanes, not 8-OHdG, were positively associated with MetS. Conclusion. The weak correlation between 8-OHdG and F2-isoprostanes suggests they reflect specific aspects of oxidative stress. Both markers are associated with a range of sociodemographic, lifestyle, and sampling determinants which should be considered in future research. F2 isoprostanes are associated with MetS. PMID- 27006749 TI - Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects. AB - Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings. PMID- 27006750 TI - Sulforaphane Attenuates Contrast-Induced Nephropathy in Rats via Nrf2/HO-1 Pathway. AB - Background. Oxidative stress plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of this study was to investigate the antioxidant effects of sulforaphane (SFN) in a rat model of CIN and a cell model of oxidative stress in HK2 cells. Methods. Rats were randomized into four groups (n = 6 per group): control group, Ioversol group (Ioversol-induced CIN), Ioversol + SFN group (CIN rats pretreated with SFN), and SFN group (rats treated with SFN). Renal function tests, malondialdehyde (MDA), and reactive oxygen species (ROS) were measured. Western blot, real-time polymerase chain reaction analysis, and immunohistochemical analysis were performed for nuclear factor erythroid derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) detection. Results. Serum blood urea nitrogen (BUN), creatinine, and renal tissue MDA were increased after contrast exposure. Serum BUN, creatinine, and renal tissue MDA were decreased in the Ioversol + SFN group as compared with those in the Ioversol group. SFN increased the expression of Nrf2 and HO-1 in CIN rats and in Ioversol-induced injury HK2 cells. SFN increased cell viability and attenuated ROS level in vitro. Conclusions. SFN attenuates experimental CIN in vitro and in vivo. This effect is suggested to activate the Nrf2 antioxidant defenses pathway. PMID- 27006751 TI - Allergen immunotherapy for allergic rhinoconjunctivitis: protocol for a systematic review. AB - BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. CONCLUSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT. PMID- 27006753 TI - Metagenomic Chromosome Conformation Capture (3C): techniques, applications, and challenges. AB - We review currently available technologies for deconvoluting metagenomic data into individual genomes that represent populations, strains, or genotypes present in the community. An evaluation of chromosome conformation capture (3C) and related techniques in the context of metagenomics is presented, using mock microbial communities as a reference. We provide the first independent reproduction of the metagenomic 3C technique described last year, propose some simple improvements to that protocol, and compare the quality of the data with that provided by the more complex Hi-C protocol. PMID- 27006752 TI - Dissecting microRNA-mediated regulation of stemness, reprogramming, and pluripotency. AB - Increasing evidence indicates that microRNAs (miRNAs), endogenous short non coding RNAs 19-24 nucleotides in length, play key regulatory roles in various biological events at the post-transcriptional level. Embryonic stem cells (ESCs) represent a valuable tool for disease modeling, drug discovery, developmental studies, and potential cell-based therapies in regenerative medicine due to their unlimited self-renewal and pluripotency. Therefore, remarkable progress has been made in recent decades toward understanding the expression and functions of specific miRNAs in the establishment and maintenance of pluripotency. Here, we summarize the recent knowledge regarding the regulatory roles of miRNAs in self renewal of pluripotent ESCs and during cellular reprogramming, as well as the potential role of miRNAs in two distinct pluripotent states (naive and primed). PMID- 27006754 TI - Defining the functional states of Th17 cells. AB - The molecular mechanisms governing T helper (Th) cell differentiation and function have revealed a complex network of transcriptional and protein regulators. Cytokines not only initiate the differentiation of CD4 Th cells into subsets but also influence the identity, plasticity and effector function of a T cell. Of the subsets, Th17 cells, named for producing interleukin 17 (IL-17) as their signature cytokine, secrete a cohort of other cytokines, including IL-22, IL-21, IL-10, IL-9, IFNgamma, and GM-CSF. In recent years, Th17 cells have emerged as key players in host defense against both extracellular pathogens and fungal infections, but they have also been implicated as one of the main drivers in the pathogenesis of autoimmunity, likely mediated in part by the cytokines that they produce. Advances in high throughput genomic sequencing have revealed unexpected heterogeneity in Th17 cells and, as a consequence, may have tremendous impact on our understanding of their functional diversity. The assortment in gene expression may also identify different functional states of Th17 cells. This review aims to understand the interplay between the cytokine regulators that drive Th17 cell differentiation and functional states in Th17 cells. PMID- 27006755 TI - Fatty acids from diet and microbiota regulate energy metabolism. AB - A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system. PMID- 27006756 TI - Chemoprevention of cancer: current evidence and future prospects. AB - Cancer chemoprevention refers to the use of agents for the inhibition, delay, or reversal of carcinogenesis before invasion. In the present review, agents examined in the context of cancer chemoprevention are classified in four major categories-hormonal, medications, diet-related agents, and vaccines-and the main representatives of each category are presented. Although there are serious constraints in the documentation of effectiveness of chemopreventive agents, mainly stemming from the long latency of the condition they are addressing and the frequent lack of intermediate biomarkers, there is little disagreement about the role of aspirin, whereas a diet rich in vegetables and fruits appears to convey more protection than individual micronutrients. Among categories of cancer chemopreventive agents, hormonal ones and vaccines might hold more promise for the future. Also, the identification of individuals who would benefit most from chemopreventive interventions on the basis of their genetic profiles could open new prospects for cancer chemoprevention. PMID- 27006757 TI - The life cycle of a genome project: perspectives and guidelines inspired by insect genome projects. AB - Many research programs on non-model species biology have been empowered by genomics. In turn, genomics is underpinned by a reference sequence and ancillary information created by so-called "genome projects". The most reliable genome projects are the ones created as part of an active research program and designed to address specific questions but their life extends past publication. In this opinion paper I outline four key insights that have facilitated maintaining genomic communities: the key role of computational capability, the iterative process of building genomic resources, the value of community participation and the importance of manual curation. Taken together, these ideas can and do ensure the longevity of genome projects and the growing non-model species community can use them to focus a discussion with regards to its future genomic infrastructure. PMID- 27006758 TI - Perioperative sleep apnea: a real problem or did we invent a new disease? AB - Depending on the subpopulation, obstructive sleep apnea (OSA) can affect more than 75% of surgical patients. An increasing body of evidence supports the association between OSA and perioperative complications, but some data indicate important perioperative outcomes do not differ between patients with and without OSA. In this review we will provide an overview of the pathophysiology of sleep apnea and the risk factors for perioperative complications related to sleep apnea. We also discuss a clinical algorithm for the identification and management of OSA patients facing surgery. PMID- 27006760 TI - Nanoparticle-Based Antimicrobials: Surface Functionality is Critical. AB - Bacterial infections cause 300 million cases of severe illness each year worldwide. Rapidly accelerating drug resistance further exacerbates this threat to human health. While dispersed (planktonic) bacteria represent a therapeutic challenge, bacterial biofilms present major hurdles for both diagnosis and treatment. Nanoparticles have emerged recently as tools for fighting drug resistant planktonic bacteria and biofilms. In this review, we present the use of nanoparticles as active antimicrobial agents and drug delivery vehicles for antibacterial therapeutics. We further focus on how surface functionality of nanomaterials can be used to target both planktonic bacteria and biofilms. PMID- 27006759 TI - Metals and Neurodegeneration. AB - Metals play important roles in the human body, maintaining cell structure and regulating gene expression, neurotransmission, and antioxidant response, to name a few. However, excessive metal accumulation in the nervous system may be toxic, inducing oxidative stress, disrupting mitochondrial function, and impairing the activity of numerous enzymes. Damage caused by metal accumulation may result in permanent injuries, including severe neurological disorders. Epidemiological and clinical studies have shown a strong correlation between aberrant metal exposure and a number of neurological diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, autism spectrum disorders, Guillain-Barre disease, Gulf War syndrome, Huntington's disease, multiple sclerosis, Parkinson's disease, and Wilson's disease. Here, we briefly survey the literature relating to the role of metals in neurodegeneration. PMID- 27006761 TI - Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease. AB - Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population. PMID- 27006762 TI - Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules. AB - Major histocompatibility complex (MHC) class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of naive T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these) to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes) and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II alpha and beta chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail) mediates these "non traditional" class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease. PMID- 27006765 TI - Corrigendum to 'A rare case of fibrostenotic endobronchial tuberculosis of trachea' [Ann. Med. Surg. 4 (2015) 479-482]. AB - [This corrects the article DOI: 10.1016/j.amsu.2015.10.007.]. PMID- 27006763 TI - A systematic review and meta-analysis of perioperative oral decontamination in patients undergoing major elective surgery. AB - BACKGROUND: Oral antiseptics reduce nosocomial infections and ventilator associated pneumonia in critically ill medical and surgical patients intubated for prolonged periods. However, the role of oral antiseptics given before and after planned surgery is not clear. The aim of this systematic review and meta analysis is to determine the effect of oral antiseptics (chlorhexidine or povidone-iodine) when administered before and after major elective surgery. METHODS: Searches were conducted of the MEDLINE, EMBASE and Cochrane databases. The analysis was performed using the random-effects method and the risk ratio (RR) with 95 % confidence interval (CI). RESULTS: Of 1114 unique identified articles, perioperative chlorhexidine was administered to patients undergoing elective surgery in four studies. This identified 2265 patients undergoing elective cardiac surgery, of whom 1093 (48.3 %) received perioperative chlorhexidine. Postoperative pneumonia and nosocomial infections were observed in 5.3 and 20.2 % who received chlorhexidine compared to 10.4 and 31.3 % who received a control preparation, respectively. Oral perioperative chlorhexidine significantly reduced the risk of postoperative pneumonia (RR = 0.52; 95 % CI 0.39-0.71; p < 0.01) and overall nosocomial infections (RR = 0.65; 95 % CI 0.52 0.81; p < 0.01), with no effect on in-hospital mortality (RR = 1.01; 95 % CI 0.49 2.09; p = 0.98). CONCLUSIONS: Perioperative oral chlorhexidine significantly decreases the incidence of nosocomial infection and postoperative pneumonia in patients undergoing elective cardiac surgery. There are no randomised controlled studies of this simple and cheap intervention in patients undergoing elective non cardiac surgery. TRIAL REGISTRATION: This systematic review was registered with the International prospective register of systematic reviews (PROSPERO). The registration number is CRD42015016063. PMID- 27006766 TI - A randomised controlled trial of mini incision or conventional incision for saphenous vein harvesting in patients undergoing myocardial revascularization. AB - OBJECTIVE: Compare the evolution regarding the complications concerning two types of incision (conventional * mini-incision), for saphenectomy in patients that go under myocardial revascularization or otherwise known as coronary artery bypass surgery. METHODS: In January 2012 to August 2013, 66 patients were prospectively selected for coronary artery bypass with cardiopulmonary bypass surgery. These were divided into two groups: Conventional and Mini-Incision, with 33 patients in each group chosen in a random fashion and with knowledge of which technique to be used being presented only at the start of the surgery. In the conventional group, the patients received an incision to the lower member of 7-10 cm. The patients in the Mini-Incision group received an incision to the lower member of 3-4 cm, both performed without the use of any special material. RESULTS: The groups were similar in terms of clinical data and in the preoperative period. Males made up a greater part of the group with 63.7% and 81.9% in groups C and M, respectively. Among the complications analysed, edema (p = 0.011), hematoma (p = 0.020), dehiscence (p = 0.012) and infection (p = 0.012), were significantly greater in group C when compared to group M. When the matter comes to the variable in relation to the risk of Surgical Site Infections (SSI), no difference was found between the groups. CONCLUSION: Coronary artery bypass surgery with mini-incision for saphenectomy, demonstrated a lower rate for preoperative complications when compared to saphenectomy under conventional incision procedures. PMID- 27006764 TI - Mitochondrial metagenomics: letting the genes out of the bottle. AB - 'Mitochondrial metagenomics' (MMG) is a methodology for shotgun sequencing of total DNA from specimen mixtures and subsequent bioinformatic extraction of mitochondrial sequences. The approach can be applied to phylogenetic analysis of taxonomically selected taxa, as an economical alternative to mitogenome sequencing from individual species, or to environmental samples of mixed specimens, such as from mass trapping of invertebrates. The routine generation of mitochondrial genome sequences has great potential both for systematics and community phylogenetics. Mapping of reads from low-coverage shotgun sequencing of environmental samples also makes it possible to obtain data on spatial and temporal turnover in whole-community phylogenetic and species composition, even in complex ecosystems where species-level taxonomy and biodiversity patterns are poorly known. In addition, read mapping can produce information on species biomass, and potentially allows quantification of within-species genetic variation. The success of MMG relies on the formation of numerous mitochondrial genome contigs, achievable with standard genome assemblers, but various challenges for the efficiency of assembly remain, particularly in the face of variable relative species abundance and intra-specific genetic variation. Nevertheless, several studies have demonstrated the power of mitogenomes from MMG for accurate phylogenetic placement, evolutionary analysis of species traits, biodiversity discovery and the establishment of species distribution patterns; it offers a promising avenue for unifying the ecological and evolutionary understanding of species diversity. PMID- 27006767 TI - Role of MicroRNAs in carcinogenesis that potential for biomarker of endometrial cancer. AB - The non-invasive diagnostic tool for early detection of endometrial cancer still limited. The etiology of this disease is believed to be associated with disharmony hormone production. One predominant factor that regulate hormone production is microRNA (miRNAs). Some studies reported that miRNAs play a significant role in the process carcinogenesis. We have identified 12 of miRNAs that potentially have a role in controlling endometrial carcinogenesis pathways. Further analysis suggested that these miRNA targeted genes that regulate the early development of endometrial cancer. These genes cluster into several functional groups involving a process of angiogenesis, apoptosis, cell cycle, cell proliferation and p53 pathways. Some of the genes are PTEN, GSK3b, and TP53, which are a tumor suppressor that control the process of growth arrest, DNA Repair, and Apoptosis. Upregulation of the miRNA may obstruct the cell ability to control the cell cycle. This study was found three miRNA that plays a role in the development of endometrial cancer. The hsa-miR-495 and hsa-miR-152 were repressed in endometrial cancer compared to normal tissue. The microRNA regulate genes that control proliferation and cell survival. Moreover, hsa-miR-181d was upregulated to control expression a tumor suppressor gene, PTEN to protect the cancer cell from apoptosis. Further investigation to validate the function of the miRNA is a warrant for developing biomarkers of endometrial carcinoma. PMID- 27006769 TI - Widening the reach of structural biology. AB - An exciting future is outlined in which new approaches complementary to conventional X-ray crystallography will substantially widen the reach of structural biology. Primary among these are the recent advances in cryoelectron microscopy and the growing applications of free electron lasers. PMID- 27006768 TI - Effects of thymol and carvacrol supplementation on intestinal integrity and immune responses of broiler chickens challenged with Clostridium perfringens. AB - BACKGROUND: Necrotic enteritis caused by Clostridium perfringens infection leads to serious economic losses in the global poultry production. In the present study, we investigated the protective effects of essential oils (EO, which contained 25 % thymol and 25 % carvacrol as active components) supplementation on growth performance, gut lesions, intestinal morphology, and immune responses of the broiler chickens infected with C. perfringens. A total of 448 1-day-old male broiler chicks were allocated into eight treatment groups following a 4 * 2 factorial arrangement with four dietary EO dosages (0, 60, 120, or 240 mg/kg) and two infection status (with or without C. perfringens challenge from d 14 to 20). RESULTS: The challenge did not impair the growth performance of birds, but induced gut lesions and increased crypt depth in the ileum (P <= 0.05). It also down-regulated the claudin-1 and occludin mRNA expression (P <= 0.05), up regulated the mRNA expression of interleukin-1beta (P <= 0.05), tended to increase the toll-like receptor (TLR) 2 mRNA expression (P < 0.10) in the ileum, and enhanced the mucosal secretory IgA production (P <= 0.05). In the challenged birds, dietary EO supplementation linearly alleviated the gut lesions and improved the ratio of villus height to crypt depth (P <= 0.05), and the supplementation of 120 and 240 mg/kg EO increased the serum antibody titers against Newcastle disease virus (P <= 0.05). Regardless of challenge, the EO supplementation showed a tendency to linearly elevate the feed conversion efficiency between 14 and 28 d of age as well as the occludin mRNA expression (P < 0.10), and linearly inhibited the mRNA expression of TLR2 and tumor necrotic factor-alpha in the ileum (P <= 0.05). CONCLUSIONS: The dietary supplementation of EO could alleviate the intestinal injury by improving intestinal integrity and modulating immune responses in the C. perfringens-challenged broiler chickens. PMID- 27006770 TI - Cracks observed to propagate discontinuously on the millisecond timescale. AB - Ultra-fast diffraction and phase contrast imaging experiments on crack propagation in silicon, reported in the current issue of IUCrJ, are reviewed in the light of our present knowledge and its industrial importance. PMID- 27006772 TI - Four- and five-component molecular solids: crystal engineering strategies based on structural inequivalence. AB - A synthetic strategy is described for the co-crystallization of four- and five component molecular crystals, based on the fact that if any particular chemical constituent of a lower cocrystal is found in two different structural environments, these differences may be exploited to increase the number of components in the solid. 2-Methylresorcinol and tetramethylpyrazine are basic template molecules that allow for further supramolecular homologation. Ten stoichiometric quaternary cocrystals and one quintinary cocrystal with some solid solution character are reported. Cocrystals that do not lend themselves to such homologation are termed synthetic dead ends. PMID- 27006771 TI - In cellulo serial crystallography of alcohol oxidase crystals inside yeast cells. AB - The possibility of using femtosecond pulses from an X-ray free-electron laser to collect diffraction data from protein crystals formed in their native cellular organelle has been explored. X-ray diffraction of submicrometre-sized alcohol oxidase crystals formed in peroxisomes within cells of genetically modified variants of the methylotrophic yeast Hansenula polymorpha is reported and characterized. The observations are supported by synchrotron radiation-based powder diffraction data and electron microscopy. Based on these findings, the concept of in cellulo serial crystallography on protein targets imported into yeast peroxisomes without the need for protein purification as a requirement for subsequent crystallization is outlined. PMID- 27006773 TI - Quaternary cocrystals: combinatorial synthetic strategies based on long-range synthon Aufbau modules (LSAM). AB - A synthetic strategy is outlined whereby a binary cocrystal may be developed in turn into a ternary and finally into a quaternary cocrystal. The strategy hinges on the concept of the long-range synthon Aufbau module (LSAM) which is a large supramolecular synthon containing more than one type of intermolecular interaction. Modulation of these interactions may be possible with the use of additional molecular components so that higher level cocrystals are produced. We report six quaternary cocrystals here. All are obtained as nearly exclusive crystallization products when four appropriate solid compounds are taken together in solution for crystallization. PMID- 27006774 TI - Real-time direct and diffraction X-ray imaging of irregular silicon wafer breakage. AB - Fracture and breakage of single crystals, particularly of silicon wafers, are multi-scale problems: the crack tip starts propagating on an atomic scale with the breaking of chemical bonds, forms crack fronts through the crystal on the micrometre scale and ends macroscopically in catastrophic wafer shattering. Total wafer breakage is a severe problem for the semiconductor industry, not only during handling but also during temperature treatments, leading to million-dollar costs per annum in a device production line. Knowledge of the relevant dynamics governing perfect cleavage along the {111} or {110} faces, and of the deflection into higher indexed {hkl} faces of higher energy, is scarce due to the high velocity of the process. Imaging techniques are commonly limited to depicting only the state of a wafer before the crack and in the final state. This paper presents, for the first time, in situ high-speed crack propagation under thermal stress, imaged simultaneously in direct transmission and diffraction X-ray imaging. It shows how the propagating crack tip and the related strain field can be tracked in the phase-contrast and diffracted images, respectively. Movies with a time resolution of microseconds per frame reveal that the strain and crack tip do not propagate continuously or at a constant speed. Jumps in the crack tip position indicate pinning of the crack tip for about 1-2 ms followed by jumps faster than 2-6 m s(-1), leading to a macroscopically observed average velocity of 0.028-0.055 m s(-1). The presented results also give a proof of concept that the described X-ray technique is compatible with studying ultra-fast cracks up to the speed of sound. PMID- 27006775 TI - High-resolution neutron and X-ray diffraction room-temperature studies of an H FABP-oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution. AB - Crystal diffraction data of heart fatty acid binding protein (H-FABP) in complex with oleic acid were measured at room temperature with high-resolution X-ray and neutron protein crystallography (0.98 and 1.90 A resolution, respectively). These data provided very detailed information about the cluster of water molecules and the bound oleic acid in the H-FABP large internal cavity. The jointly refined X ray/neutron structure of H-FABP was complemented by a transferred multipolar electron-density distribution using the parameters of the ELMAMII library. The resulting electron density allowed a precise determination of the electrostatic potential in the fatty acid (FA) binding pocket. Bader's quantum theory of atoms in molecules was then used to study interactions involving the internal water molecules, the FA and the protein. This approach showed H?H contacts of the FA with highly conserved hydrophobic residues known to play a role in the stabilization of long-chain FAs in the binding cavity. The determination of water hydrogen (deuterium) positions allowed the analysis of the orientation and electrostatic properties of the water molecules in the very ordered cluster. As a result, a significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field was observed. This can be related to the dielectric properties of hydration layers around proteins, where the shielding of electrostatic interactions depends directly on the rotational degrees of freedom of the water molecules in the interface. PMID- 27006776 TI - Whole-pattern fitting technique in serial femtosecond nanocrystallography. AB - Serial femtosecond X-ray crystallography (SFX) has created new opportunities in the field of structural analysis of protein nanocrystals. The intensity and timescale characteristics of the X-ray free-electron laser sources used in SFX experiments necessitate the analysis of a large collection of individual crystals of variable shape and quality to ultimately solve a single, average crystal structure. Ensembles of crystals are commonly encountered in powder diffraction, but serial crystallography is different because each crystal is measured individually and can be oriented via indexing and merged into a three-dimensional data set, as is done for conventional crystallography data. In this way, serial femtosecond crystallography data lie in between conventional crystallography data and powder diffraction data, sharing features of both. The extremely small sizes of nanocrystals, as well as the possible imperfections of their crystallite structure, significantly affect the diffraction pattern and raise the question of how best to extract accurate structure-factor moduli from serial crystallography data. Here it is demonstrated that whole-pattern fitting techniques established for one-dimensional powder diffraction analysis can be feasibly extended to higher dimensions for the analysis of merged SFX diffraction data. It is shown that for very small crystals, whole-pattern fitting methods are more accurate than Monte Carlo integration methods that are currently used. PMID- 27006777 TI - The crystalline sponge method updated. AB - Crystalline sponges are porous metal complexes that can absorb and orient common organic molecules in their pores and make them observable by conventional X-ray structure analysis (crystalline sponge method). In this study, all of the steps in the crystalline sponge method, including sponge crystal preparation, pore solvent exchange, guest soaking, data collection and crystallographic analysis, are carefully examined and thoroughly optimized to provide reliable and meaningful chemical information as chemical crystallography. Major improvements in the method have been made in the guest-soaking and data-collection steps. In the soaking step, obtaining a high site occupancy of the guest is particularly important, and dominant parameters for guest soaking (e.g. temperature, time, concentration, solvents) therefore have to be optimized for every sample compound. When standard conditions do not work, a high-throughput method is useful for efficiently optimizing the soaking conditions. The X-ray experiments are also carefully re-examined. Significant improvement of the guest data quality is achieved by complete data collection at high angle regions. The appropriate disorder treatment of the most flexible ZnI2 portions of the host framework and refinement of the solvents filling the remaining void are also particularly important for obtaining better data quality. A benchmark test for the crystalline sponge method toward an achiral molecule is proposed with a guaiazulene guest, in which the guest structure (with ~ 100% site occupancy) is refined without applying any restraints or constraints. The obtained data quality with R int = 0.0279 and R 1 = 0.0379 is comparable with that of current conventional crystallographic analysis for small molecules. Another benchmark test for this method toward a chiral molecule is also proposed with a santonin guest. The crystallographic data obtained [R int = 0.0421, R 1 = 0.0312, Flack (Parsons) = 0.0071 (11)] represents the potential ability of this method for reliable absolute structure determination. PMID- 27006778 TI - Binary and ternary cocrystals of sulfa drug acetazolamide with pyridine carboxamides and cyclic amides. AB - A novel design strategy for cocrystals of a sulfonamide drug with pyridine carboxamides and cyclic amides is developed based on synthon identification as well as size and shape match of coformers. Binary adducts of acetazolamide (ACZ) with lactams (valerolactam and caprolactam, VLM, CPR), cyclic amides (2-pyridone, labeled as 2HP and its derivatives MeHP, OMeHP) and pyridine amides (nicotinamide and picolinamide, NAM, PAM) were obtained by manual grinding, and their single crystals by solution crystallization. The heterosynthons in the binary cocrystals of ACZ with these coformers suggested a ternary combination for ACZ with pyridone and nicotinamide. Novel supramolecular synthons of ACZ with lactams and pyridine carboxamides are reported together with binary and ternary cocrystals for a sulfonamide drug. This crystal engineering study resulted in the first ternary cocrystal of acetazolamide with amide coformers, ACZ-NAM-2HP (1:1:1). PMID- 27006779 TI - Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness. AB - Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm. PMID- 27006780 TI - Evaluating long-latency auditory evoked potentials in the diagnosis of cortical hearing loss in children. AB - In centrally related hearing loss, there is no apparent damage in the auditory system, but the patient is unable to hear sounds. In patients with cortical hearing loss (and in the absence of communication deficit, either total or partial, as in agnosia or aphasia), some attention-related or language-based disorders may lead to a wrong diagnosis of hearing impairment. The authors present two patients (8 and 11 years old) with no anatomical damage to the ear, the absence of neurological damage or trauma, but immature cortical auditory evoked potentials. Both patients presented a clinical history of multiple diagnoses over several years. Because the most visible symptom was moderate hearing loss, the patients were recurrently referred to audiological testing, with no improvement. This report describes the use of long-latency evoked potentials to determine cases of cortical hearing loss, where hearing impairment is a consequence of underdevelopment at the central nervous system. PMID- 27006781 TI - Comparative effectiveness of home dialysis therapies: a matched cohort study. AB - BACKGROUND: Home dialysis is being increasingly promoted among patients with end stage renal disease, but the comparative effectiveness of home hemodialysis and peritoneal dialysis is unknown. OBJECTIVE: To determine whether patients receiving home daily hemodialysis have reduced mortality risk compared with matched patients receiving home peritoneal dialysis. DESIGN: This study is an observational, propensity-matched, new-user cohort study. SETTING: Linked electronic data were from the United States Renal Data System (USRDS) and a large dialysis provider's database. PATIENTS: The patients were adults receiving in center hemodialysis in the USA between 2004 and 2011 and registered in the USRDS. MEASUREMENTS: Baseline comorbidities, demographics, and outcomes for both groups were ascertained from the United States Renal Data System. METHODS: We identified 3142 consecutive adult patients initiating home daily hemodialysis (>=5 days/week for >=1.5 h/day) and matched 2688 of them by propensity score to 2688 contemporaneous US patients initiating home peritoneal dialysis. We used Cox regression to compare all-cause mortality between groups. RESULTS: After matching, the two groups were well balanced on all baseline characteristics. Mean age was 51 years, 66 % were male, 72 % were white, and 29 % had diabetes. During 10,221 patient-years of follow-up, 1493/5336 patients died. There were significantly fewer deaths among patients receiving home daily hemodialysis than those receiving peritoneal dialysis (12.7 vs 16.7 deaths per 100 patient-years, respectively; hazard ratio (HR) 0.75; 95 % CI 0.68-0.82; p < 0.001). Similar results were noted with several different analytic methods and for all pre specified subgroups. LIMITATIONS: We cannot exclude residual confounding in this observational study. CONCLUSIONS: Home daily hemodialysis was associated with lower mortality risk than home peritoneal dialysis. PMID- 27006782 TI - A meta-analysis of the success rates of heartbeat restoration within the platinum 10 min among outpatients suffering from sudden cardiac arrest in China. AB - BACKGROUND: The optimal time to save a person who has had a sudden cardiac arrest is within the first few minutes of the incident. Early compression and early defibrillation should be performed at this time. Timeliness is the key to successful CPR; as such, Prof. He proposed the "platinum 10 min" system to study early CPR issues. This paper systematically evaluates the success rates of heartbeat restoration within the "platinum 10 min" among patients suffering from sudden cardiac arrest. METHODS: The clinical data of outpatients suffering from a cardiac arrest were retrieved from the China Knowledge Network (January 1975 January 2015), the Chongqing VIP database (January 1989-January 2015), and the Wanfang database (January 1990-January 2015). The success of the cardiopulmonary resuscitation (CPR) performed at different times after the patients had cardiac arrests was analyzed. Two researchers screened the literature and extracted the data independently. A meta-analysis was conducted using Stata12.0. A total of 57 papers met the inclusion criteria, including 29,269 patients. Of these patients, 1776 had their heartbeats successfully restored. The results showed high heterogeneity (X (2) = 3428.85, P < 0.01, I(2) = 98.4 %). The meta-analysis was conducted using a random-effects model. The combined effect size was 0.171 (0.144 0.199). RESULTS: (1) The success rate of heartbeat restoration did not differ among the four emergency treatment methods that patients received: the methods described in the 2000 Guidelines for CPR and Emergency Cardiovascular Care, that described in the 2005 version, 2010 version, and another CPR method. (2) The patients were divided into five groups based on the time when CPR was performed: the <=1 min group, the 1- <= 5 min group, the 5- <= 10 min group, the 10- <= 15 min group and the >15 min group. The CPR success rates of these five groups were 0.247 (0.15-0.344), 0.353 (0.250-0.456), 0.136 (0.109-0.163), 0.058 (0.041 0.075), and 0.011 (0.004-0.019), respectively. The CPR success rates did not differ between the patients in the <=1 min group and the 1- <= 5 min group. This success rate was higher for the patients in the 1- <= 5 min group than those in the 10- <= 15 min group, those in the 10- <= 15 min group, and those in the >15 min group. The CPR success rate was higher for the patients in the 5-10 min group than those in the 10- <= 15 min group and those in the >15 min group. CONCLUSIONS: The CPR success rate was higher for the patients in the 10- <= 15 min group than those in the >15 min group. In addition, the patients were divided into two groups based on whether CPR was performed within the first 10 min after the cardiac arrest occurred: the <=10 min group and the >10 min group. The CPR success rate was higher for the patients in the <=10 min group (0.189 [0.161 0.218]) than those in the >10 min group (0.044 [0.032-0.056]). (3) Differences were not found between the CPR success rates among the patients in the telephone guidance group (0.167 [0.016-0.351]) and those in the <=1 min, 1- <= 5 min, 5- <= 10 min, 10- <= 15 min, and >15 min groups. (4) The CPR success rates did not differ among in the patients in the witness + public group (0.329 [0.221-0.436]), those in the <=1 min group, and those in the 1- <= 5 min group. However, this success rate was higher in the patients in the witness + public group than those in the 5- <= 10 min, 10- <= 15 min, and >15 min groups. CONCLUSIONS: The success rate of heartbeat restoration did not differ among patients receiving CPR based on different guidelines. The success rate of CPR lies in its timeliness. The participation of the general population is the cornerstone of improving CPR. Providing complete emergency treatment equipment and perfecting comprehensive measures can improve the success rate of CPR among patients within the platinum 10 min. CPR research in China must be improved. PMID- 27006783 TI - Mode of reduction in the number of pharyngeal segments within the sarcopterygians. AB - BACKGROUND: Pharyngeal segmentation is a defining feature of vertebrate embryos and is apparent as a series of bulges found on the lateral surface of the embryonic head, the pharyngeal arches. The ancestral condition for gnathostomes is to have seven pharyngeal segments: jaw, hyoid, and five posterior branchial arches. However, within the sarcopterygians, the pharyngeal region has undergone extensive remodelling that resulted in a reduction in the number of pharyngeal segments, such that amniotes have only five pharyngeal arches. The aim of this study is to probe the developmental basis of this loss of pharyngeal segments. RESULTS: We have therefore compared the development of the pharyngeal arches in an amniote, the chick, which has five segments, with those of a chondrichthyan, the catshark, which has seven segments. We have analysed the early phase of pharyngeal segmentation and we find that in both the most anterior segments form first with the posterior segments being added sequentially. We also documented the patterns of innervation of the pharynx in several vertebrates and note that the three most anterior segments receive distinct innervation: the first arch being innervated by the Vth nerve, the second by the VIIth and the third by the IXth. Finally, we have analysed Hox gene expression, and show that the anterior limit of Hoxa2 aligns with the second pouch and arch in both chick and catshark, while Hoxa3 is transiently associated with the third arch and pouch. Surprisingly, we have found that Hoxb1 expression is spatially and temporally dynamic and that it is always associated with the last most recently formed pouch and that this domains moves caudally as additional pouches are generated. CONCLUSION: We propose that the first three pharyngeal segments are homologous, as is the posterior limit of the pharynx, and that the loss of segments occurred between these two points. We suggest that this loss results from a curtailment of the posterior expansion of the pharyngeal endoderm in amniotes at relatively earlier time point, and thus the generation of fewer segments. PMID- 27006784 TI - Crystal structure of bis-(1,4-di-aza-bicyclo-[2.2.2]octan-1-ium) thio-sulfate dihydrate. AB - The crystal structure of the hydrated title salt, 2C6H13N2 (+).S2O3 (2-).2H2O, contains a centrosymmetric cyclic motif of eight hydrogen-bonded mol-ecular subunits. Two DABCOH(+) cations (DABCO = 1,4-di-aza-bicyclo-[2.2.2]octa-ne) are linked to two water mol-ecules and two thio-sulfate anions via O-H?N and O-H?O hydrogen bonds, respectively. Two other water mol-ecules close the cyclic motif through O-H?O contacts to the first two water mol-ecules and to the two thio sulfate anions. A second pair of DABCOH(+) cations is N-H?O hydrogen bonded to the two anions and is pendant to the ring. Adjacent cyclic motifs are bridged into a block-like arrangement extending along [100] through O-H?O inter-actions involving the second pair of water mol-ecules and neighbouring thio-sulfate anions. PMID- 27006785 TI - Crystal structure of the 1:1 adduct of 2,3-diphenyl-3,4,5,6-tetra-hydro-2H-1,3 thia-zin-4-one with tri-phenyl-tin chloride. AB - The title adduct, chlorido-(2,3-diphenyl-3,4,5,6-tetra-hydro-2H-1,3-thia-zin-4 one-kappaO)tri-phenyl-tin, [Sn(C6H5)3Cl(C16H15NOS)], resulted from reaction of 2,3-diphenyl-3,4,5,6-tetra-hydro-2H-1,3-thia-zin-4-one with tri-phenyl-tin chloride. The thia-zine ring has an envelope conformation with the S atom forming the flap. The mol-ecule has five phenyl rings, two of them attached to the thia zine ring at positions 2 and 3, and three in coordination with the Sn(IV) atom. The three rings of the tri-phenyl-tin group are involved in intra-molecular inter actions of different types, C-H?O, edge-to-face (or T-type) pi-pi inter-actions with the 3-phenyl ring of the thia-zine, T-type inter-actions with both phenyl rings of the thia-zine etc. On the other hand, all the phenyl rings participate in inter-molecular pi-pi inter-actions. There is one instance of a 'parallel displaced'-type inter-action extending continuously along the a-axis direction and seven instances of T-type inter-actions stabilizing the crystal lattice. PMID- 27006786 TI - Crystal structure of cis-aqua-bis-(2,2'-bi-pyridine-kappa(2) N,N')chlorido chromium(III) tetra-chlorido-zincate determined from synchrotron data. AB - The structure of the title salt, [CrCl(C10H8N2)2(H2O)][ZnCl4], has been determined from synchrotron data. The Cr(III) ion is coordinated by four N atoms from two 2,2'-bi-pyridine (bipy) ligands, one O atom from a water mol-ecule and a chloride anion in a cis arrangement, displaying a distorted octa-hedral geometry. The tetra-hedral [ZnCl4](2-) anion is slightly distorted owing to its involvement in O-H?Cl hydrogen bonding with the coordinating water mol-ecule. The Cr-N(bipy) bond lengths are in the range 2.0485 (13)-2.0632 (12) A, while the Cr-Cl and Cr (OH2) bond lengths are 2.2732 (6) and 1.9876 (12) A, respectively. In the crystal, mol-ecules are stacked along the a axis. PMID- 27006787 TI - Crystal structure of 3-{5-[3-(4-fluoro-phen-yl)-1-isopropyl-1H-indol-2-yl]-1H pyrazol-1-yl}indolin-2-one ethanol monosolvate. AB - The title indolin-2-one compound, C28H23FN4O.C2H6O, crystallizes as a 1:1 ethanol solvate. The ethanol mol-ecule is disordered over two positions with refined site occupancies of 0.560 (14) and 0.440 (14). The pyrazole ring makes dihedral angles of 84.16 (10) and 85.33 (9) degrees with the indolin-2-one and indole rings, respectively, whereas the dihedral angle between indolin-2-one and indole rings is 57.30 (7) degrees . In the crystal, the components are linked by N-H?O and O H?O hydrogen bonds, forming an inversion mol-ecule-solvate 2:2 dimer with R 4 (4)(12) ring motifs. The crystal structure is consolidated by pi-pi inter-action between pairs of inversion-related indolin-2-one rings [inter-planar spacing = 3.599 (2) A]. PMID- 27006788 TI - Symmetry reduction due to gallium substitution in the garnet Li6.43(2)Ga0.52(3)La2.67(4)Zr2O12. AB - Single-crystal structure refinements on lithium lanthanum zirconate (LLZO; Li7La3Zr2O12) substituted with gallium were successfully carried out in the cubic symmetry space group I [Formula: see text]3d. Gallium was found on two lithium sites as well as on the lanthanum position. Due to the structural distortion of the resulting Li6.43(2)Ga0.52(3)La2.67(4)Zr2O12 (Ga-LLZO) single crystals, a reduction of the LLZO cubic garnet symmetry from Ia[Formula: see text] d to I [Formula: see text]3d was necessary, which could hardly be analysed from X-ray powder diffraction data. PMID- 27006789 TI - Crystal structure of S-hexyl (E)-3-(2-hy-droxy-benzyl-idene)di-thio-carbazate. AB - The title compound, C14H20N2OS2 [systematic name: S-hexyl (E)-2-(2-hy-droxy benzyl-idene)hydrazine-1-carbodi-thio-ate], crystallizes with four independent mol-ecules (A-D) in the asymmetric unit. All four mol-ecules adopt an E conformation with respect to the C=N bond of the benzyl-idene moiety and have an intra-molecular O-H?N hydrogen bond generating an S(6) ring motif. In the crystal, the A and D mol-ecules are connected by a pair N-H?S hydrogen bonds, forming a dimer with an R 2 (2)(8) ring motif. In the case of mol-ecules B and C, they are linked to themselves by pairs of N-H?S hydrogen bonds, forming B-B and C C inversion dimers with R 2 (2)(8) ring motifs. PMID- 27006790 TI - Redetermination of brackebuschite, Pb2Mn(3+)(VO4)2(OH). AB - The crystal structure of brackebuschite, ideally Pb2Mn(3+)(VO4)2(OH) [dilead(II) manganese(III) vanadate(V) hydroxide], was redetermined based on single-crystal X ray diffraction data of a natural sample from the type locality Sierra de Cordoba, Argentina. Improving on previous results, anisotropic displacement parameters for all non-H atoms were refined and the H atom located, obtaining a significant improvement of accuracy and an unambiguous hydrogen-bonding scheme. Brackebuschite belongs to the brackebuschite group of minerals with general formula A 2 M(T1O4)(T2O4)(OH, H2O), with A = Pb(2+), Ba, Ca, Sr; M = Cu(2+), Zn, Fe(2+), Fe(3+), Mn(3+), Al; T1 = As(5+), P, V(5+); and T2 = As(5+), P, V(5+), S(6+). The crystal structure of brackebuschite is based on a cubic closest-packed array of O and Pb atoms with infinite chains of edge-sharing [Mn(3+)O6] octa hedra located about inversion centres and decorated by two unique VO4 tetra-hedra (each located on a special position 2e, site symmetry m). One type of VO4 tetra hedra is linked with the (1) infinity[MnO4/2O2/1] chain by one common vertex, alternating with H atoms along the chain, while the other type of VO4 tetra-hedra link two adjacent octa-hedra by sharing two vertices with them and thereby participating in the formation of a three-membered Mn2V ring between the central atoms. The (1) infinity[Mn(3+)(VO4)2OH] chains run parallel to [010] and are held together by two types of irregular [PbO x ] polyhedra (x = 8, 11), both located on special position 2e (site symmetry m). The magnitude of the libration component of the O atoms of the (1) infinity[Mn(3+)(VO4)2OH] chain increases linearly with the distance from the centerline of the chain, indicating a significant twisting to and fro of the chain along [010]. The hy-droxy group bridges one Pb(2+) cation with two Mn(3+) cations and forms an almost linear hydrogen bond with a vanadate group of a neighbouring chain. The O?O distance of this inter-action determined from the structure refinement agrees well with Raman spectroscopic data. PMID- 27006791 TI - Crystal structure of ethyl 3-amino-6-methyl-2-[(4-methyl-phen-yl)carbamo-yl]-4 [(E)-2-phenyl-ethen-yl]thieno[2,3-b]pyridine-5-carboxyl-ate monohydrate. AB - In the title mol-ecule, C27H25N3O3S.H2O, the dihedral angle between the planes of the thienyl ring and the pendant p-tolyl group is 39.25 (6) degrees , while that between the pyridine ring and the pendant phenyl ring is 44.37 (6) degrees . In addition, there is a slight twist in the bicyclic core, with a dihedral angle of 2.39 (4) degrees between the thienyl and pyridine rings. The conformation of the carbamoyl moiety is partially determined by an intra-molecular N-H?O hydrogen bond. In the crystal, complementary N-H?O hydrogen bonds form dimers which are then associated into chains parallel to the c axis through O-H?N hydrogen bonds involving the water mol-ecule of crystallization. Electron density associated with an additional solvent mol-ecule of partial occupancy and disordered about a twofold axis was removed with the SQUEEZE procedure in PLATON [Spek (2015 ?). Acta Cryst. C71, 9-18]. The given chemical formula and other crystal data do not take into account the unknown solvent molecule(s). PMID- 27006792 TI - Crystal structure of 2-[chloro-(4-meth-oxy-phen-yl)meth-yl]-2-(4-meth-oxy-phen yl)-5,5-di-methyl-cyclo-hexane-1,3-dione. AB - In the title compound, C23H25ClO4, the cyclo-hexane ring adopts a chair conformation with the 4-meth-oxy-phenyl substituent in an axial position and the chloro-(4-meth-oxy-phen-yl)methyl substituent in an equatorial position. The packing features inversion dimers formed by pairs of C-H?O contacts and strands along [100] and [010] established by further C-H?O and C-H?Cl contacts, respectively. PMID- 27006793 TI - Structure cristalline du compose Hg3-x Sb x (S+Se)2+x I2-x (x ? 0.1). AB - Single crystals of the mercury chalcohalide Hg3-x Sb x (S+Se)2+x I2-x (x ? 0.1) (mercury anti-mony sulfide selenide iodide), were grown by a chemical transport reaction. The structure contains three independent A (Hg/Sb) atoms; each atom is strongly covalently bonded with two X (Se/S) atoms to form approximately linear X A-X units. The X-A-X units link to form A 4 X 4 rings, which are combined into infinite crankshaft-type bands running along the [100] direction. Four equatorial E (I/X = Se,S) atoms at relatively long distances complete the distorted octa hedral coordination of A (Hg/Sb). The crystal under investigation was twinned by non-merohedry with a refined twin domain fraction of 0.814 (6):0.186 (6). The structure is isotypic with Hg3Se2I2 [Beck & Hedderich (2000 ?). J. Solid State Chem. 151, 73-76], but the current determination reveals a coupled substitution, with partial replacement of Hg(+2) by Sb(+3), balanced by the equivalent substitution of I(-1) by S(-2) and Se(-2). Bond-valence calculations are consistent with this relative substitution model. PMID- 27006794 TI - Crystal structures of five 6-mercaptopurine derivatives. AB - The crystal structures of five 6-mercaptopurine derivatives, viz. 2-[(9-acetyl-9H purin-6-yl)sulfan-yl]-1-(3-meth-oxy-phen-yl)ethan-1-one (1), C16H14N4O3S, 2-[(9 acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-meth-oxy-phen-yl)ethan-1-one (2), C16H14N4O3S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-chloro-phen-yl)ethan-1 one (3), C15H11ClN4O2S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-bromo-phen yl)ethan-1-one (4), C15H11BrN4O2S, and 1-(3-meth-oxy-phen-yl)-2-[(9H-purin-6 yl)sulfan-yl]ethan-1-one (5), C14H12N4O2S. Compounds (2), (3) and (4) are isomorphous and accordingly their mol-ecular and supra-molecular structures are similar. An analysis of the dihedral angles between the purine and exocyclic phenyl rings show that the mol-ecules of (1) and (5) are essentially planar but that in the case of the three isomorphous compounds (2), (3) and (4), these rings are twisted by a dihedral angle of approximately 38 degrees . With the exception of (1) all mol-ecules are linked by weak C-H?O hydrogen bonds in their crystals. There is pi-pi stacking in all compounds. A Cambridge Structural Database search revealed the existence of 11 deposited compounds containing the 1-phenyl-2 sulfanyl-ethanone scaffold; of these, only eight have a cyclic ring as substituent, the majority of these being heterocycles. PMID- 27006795 TI - Crystal structure of 3-de-oxy-3-nitro-methyl-1,2;5,6-di-O-iso-propyl-idene-alpha d-allo-furan-ose. AB - The title compound, C13H21NO7 {systematic name: (3aR,5S,6R,6aR)-5-[(R)-2,2 dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-6-(nitro-meth-yl)tetra-hydro-furo[2,3 d][1,3]dioxole}, consists of a substituted 2,2-di-methyl-tetra-hydro-furo[2,3 d][1,3]dioxolane skeleton. The furan-ose ring A adopts a (o)T 4 conformation. The fused dioxolane ring B and the substituent dioxolane ring C also have twisted conformations. There are no strong hydrogen bonds in the crystal structure: only weak C-H?O contacts are present, which link the mol-ecules to form a three dimensional structure. PMID- 27006796 TI - Crystal structure of bis-[tetra-kis-(tri-phenyl-phosphane-kappaP)silver(I)] (nitrilo-tri-acetato-kappa(4) N,O,O',O'')(tri-phenyl-phosphane kappaP)argentate(I) with an unknown amount of methanol as solvate. AB - The structure of the title compound, [Ag(C18H15P)4]2[Ag(C6H6NO6)(C18H15P)], exhibits trigonal (P-3) symmetry, with a C 3 axis through all three complex ions, resulting in an asymmetric unit that contains one third of the atoms present in the formula unit. The formula unit thus contains two of the cations, one anion and disordered mol-ecules of methanol as the packing solvent. Attempts to refine the solvent model were unsuccessful, indicating uninter-pretable disorder. Thus, the SQUEEZE procedure in PLATON [Spek (2015 ?). Acta Cryst. C71, 9-18] was applied, accounting for 670 electrons per unit cell, representing approximately 18 mol-ecules of methanol in the formula unit. The stated crystal data for M r, MU etc do not take these into account. PMID- 27006797 TI - Crystal and mol-ecular structure of meso-2,6-di-bromo-hepta-nedioic acid (meso 2,6-di-bromo-pimelic acid). AB - The mol-ecular structure of the title compound, C7H10Br2O4, confirms the meso (2R,6S) configuration. In the crystal, mol-ecules are linked by pairs of O-H?O=C hydrogen bonds between their terminal carboxyl groups in an R 2 (2)(8) motif, forming extended chains that propagate parallel to the c axis. Adjacent chains are linked by C=O?Br halogen bonds. PMID- 27006798 TI - Crystal structure of N-[(methyl-sulfan-yl)carbon-yl]urea. AB - The almost planar (r.m.s. deviation = 0.055 A) title compound, (MeS)C(O)NHC(O)NH2, was formed during an attempted crystallization of dimethyl cyano-carbonimidodi-thio-ate with CrO2Cl2; an unexpected redox reaction converted the cyano-carbonimido moiety to a urea group and removed one methyl-thiol group. In the crystal, hydrogen-bonding inter-actions from the amide and amido N-H groups to carbonyl O atoms of neighbouring mol-ecules result in [010] ribbon-like chains. PMID- 27006799 TI - Crystal structure of dimethyl 4,4'-di-meth-oxy-biphenyl-3,3'-di-carboxyl-ate. AB - In the title compound, C18H18O6, the benzene rings are coplanar due to the centrosymmetric nature of the mol-ecule, with an inversion centre located at the midpoint of the C-C bond between the two rings. Consequently, the methyl carboxyl ate substituents are oriented in a trans fashion with regards to the bond between the benzene rings. The methyl carboxyl-ate and meth-oxy substituents are rotated slightly out of plane relative to their parent benzene rings, with dihedral and torsion angles of 18.52 (8) and -5.22 (15) degrees , respectively. The shortest O?H contact between neighbouring mol-ecules is about 2.5 A. Although some structure-directing contributions from C-H?O hydrogen-bonding inter-actions are possible, the crystal packing seems primarily directed by weak van der Waals forces. PMID- 27006800 TI - Crystal structure of 2,6-di-amino-pyridinium chloride. AB - The asymmetric unit of the title salt, C5H8N3 (+).Cl(-), comprises one half of the 2,6-di-amino-pyridinium cation (the other half being completed by the application of mirror symmetry) and one Cl(-) counter-anion, also located on the mirror plane. The amino N atom shows a significant pyramidalization, with a dihedral angle of 30.4 (14) degrees between the least-squares planes of the amino group and the non-H atoms of the 2,6-di-amino-pyridinium moiety. In the crystal, the cationic mol-ecules and Cl(-) counter-anions are arranged in sheets parallel to (001) consisting of alternating polar and non-polar parts associated with the the Cl(-) anions, pyridinium and amino moieties, and the pyridine rings, respectively. N-H?Cl inter-actions within the polar part, as well as slipped pi pi inter-actions in the non-polar part, help to establish the three-dimensional network. PMID- 27006801 TI - Crystal structure of 2-[(3aS,6R)-3,3,6-trimethyl-3,3a,4,5,6,7-hexa-hydro-2H indazol-2-yl]thia-zol-4(5H)-one. AB - The title compound, C13H19N3OS, is a new thia-zolidin-4-one derivative prepared and isolated as the pure (3aS,6R)-diastereisomer from (R)-thio-semicarbazone pulegone. It crystallized with two independent mol-ecules (A and B) in the asymmetric unit. The compound is composed of a hexhydro-indazole ring system (viz. a five-membered di-hydro-pyrazole ring fused to a cyclo-hexyl ring) with a thia-zole-4-one ring system attached to one of the pyrazole N atoms (at position 2). The overall geometry of the two mol-ecules differs slightly, with the mean planes of the pyrazole and thia-zole rings being inclined to one another by 10.4 (1) degrees in mol-ecule A and 0.9 (1) degrees in mol-ecule B. In the crystal, the A and B mol-ecules are linked via C-H?O hydrogen bonds, forming slabs parallel to the ab plane. There are C-H?pi inter-actions present within the layers, and between the layers, so forming a three-dimensional structure. PMID- 27006802 TI - Crystal structure of 1,2-bis-((benzyl-sulfan-yl){2-[1-(2-hy-droxy-phen-yl)ethyl idene]hydrazin-1-yl-idene}meth-yl)disulfane. AB - The title compound, C32H30N4O2S4, consists of two Schiff base moieties, namely two S-benzyl-beta-N-(2-hy-droxy-phenyl-ethyl-idene)di-thio-carbazate groups, which are connected through an S-S single bond. These two moieties are twisted with respect to each other, with a dihedral angle of 87.88 (4) degrees between the S2C=N planes. A bifurcated intra-molecular O-H?(N,S) hydrogen bond is observed in each moiety. In the crystal, mol-ecules are linked by pairs of C-H?O hydrogen bonds into inversion dimers. The dimers are further stacked in a column along the b axis through weak C-H?pi inter-actions. PMID- 27006803 TI - N-(2-Acetamido-2-de-oxy-beta-d-gluco-pyranos-yl)-N-(3-azido-prop-yl)-O-methyl hydroxyl-amine. AB - The structure of the title compound, C12H23N5O6, solved using adequate data from a thin crystal plate, confirmed that this useful glycoconjugate was obtained in the ring-closed beta-pyran-ose configuration with (4) C 1 conformation. The mol ecules are bound by O-H?O(OH) hydrogen bonds, notably in a zigzag C(2) chain along the short b (screw) axis, supplemented with an R 2 (2)(12) O-H?O(carbon-yl) link along the a axis and other C(2) links. The absolute configuration was not unambiguously determined but was known from the synthetic chemistry, which used natural 2-acetamido-2-de-oxy-d-glucose as the starting material. PMID- 27006804 TI - Crystal structure of (+)-methyl (E)-3-[(2S,4S,5R)-2-amino-5-hy-droxy-meth-yl-2 tri-chloro-methyl-1,3-dioxolan-4-yl]-2-methyl-prop-2-enoate. AB - In the title compound, C10H14Cl3NO5, the five-membered dioxolane ring adopts an envelope conformation. The C atom at the flap, which is bonded to the hy-droxy methyl substituent, deviates from the mean plane of other ring atoms by 0.357 (5) A. There are two intra-molecular hydrogen bonds (O-H?N and N-H?O) between the hy droxy and amino groups, so that O- and N-bound H atoms involved in these hydrogen bonds are each disordered with equal occupancies of 0.50. The methyl 2-methyl prop-2-enoate substituent also shows a disordered structure over two sets of sites with refined occupancies of 0.482 (5) and 0.518 (5). In the crystal, mol ecules are connected into a dimer by an O-H?O hydrogen bond. The dimers are further linked by N-H?O, C-H?N and C-H?O inter-actions, extending a sheet structure parallel to ([Formula: see text]01). PMID- 27006805 TI - Crystal structure of ethyl 2-[2-(4-methyl-benzo-yl)-5-p-tolyl-1H-imidazol-1 yl]acetate. AB - In the title compound, C22H22N2O3, the plane of the five-membered ring is oriented at dihedral angles of 45.4 (1) and 52.5 (1) degrees to the phenyl rings. Furthermore, this ring makes an angle of 85.2 (2) degrees with the plane of the ethyl acetate substituent. The mol-ecular structure is affected by an intra-molecular C-H?O hydrogen bond between an H atom from the p-tolyl group and the carbonyl O atom of the acetate. The methyl group of the ethyl acetate residue is disordered over two sites with equal occupancies. The crystal structure features inter-molecular C-H?O and C-H?N inter-actions. One of the C-H?O hydrogen bonds forms a C(5) chain motif extending along the a axis. In addition, C-H?N contacts form inversion dimers with R 2 (2)(12) ring motifs, linking the imidazole ring system to the benzene ring of the p-tolyl substituent. PMID- 27006806 TI - Crystal structures of four chiral imine-substituted thio-phene derivatives. AB - A series of thio-phenes substituted in positions 2 and 5 by imine groups have been synthesized using a solvent-free approach, and their crystal structures determined. The substituents are chiral groups, and the expected absolute configuration for each mol-ecule was confirmed by refinement of the Flack parameter. The compounds are 2,5-bis-[(S)-(+)-(1,2,3,4-tetra-hydro-naphthalen-1 yl)imino]-thio-phene, C26H26N2S, (I), 2,5-bis-{[(R)-(-)-1-(4-meth-oxy-phen-yl)eth yl]imino-meth-yl}thio-phene, C24H26N2O2S, (II), 2,5-bis-{[(R)-(-)-1-(4-fluoro phen-yl)eth-yl]imino-meth-yl}thio-phene, C22H20F2N2S, (III), and 2,5-bis-{[(S) (+)-1-(4-chloro-phen-yl)eth-yl]imino-meth-yl}thio-phene, C22H20Cl2N2S, (IV). A common feature of all four mol-ecules is the presence of twofold symmetry. For (I), which crystallizes in the triclinic space group P1, this symmetry is non crystallographic, but for (II) in C2 and the isomorphous structures (III) and (IV) that crystallize in P21212, the twofold symmetry is crystallographically imposed with one half of each mol-ecule in the asymmetric unit. The comparable mol-ecular symmetry in the four structures is also reflected in similar packing, with mol-ecules aggregated to form chains through weak C-H?S inter-actions. PMID- 27006807 TI - Crystal structure of bis-(2-methyl-1H-imidazol-3-ium) di-hydroxidobis(oxalato kappa(2) O (1),O (2))stannate(IV) monohydrate. AB - In the structure of the hydrated title salt, (C4H7N2)2[Sn(C2O4)2(OH)2].H2O, the asymmetric unit comprises one stannate(IV) dianion, two organic cations and one water mol-ecule of crystallization. The [Sn(C2O4)2(OH)2](2-) dianion consists of an Sn(IV) atom chelated by two oxalate anions and coordinated by two OH(-) ligands in a cis octa-hedral arrangement. Neighbouring anions are connected through O-H?O hydrogen bonds between hydroxide groups and non-coordinating oxalate O atoms into layers expanding parallel to (100). In addition, cations and anions are linked through N-H?O hydrogen bonds, and the water mol-ecule bridges two anions with two O-H?O hydrogen bonds and is also the acceptor of an N-H?O hydrogen bond with one of the cations. Weak C-H?O hydrogen bonds are also observed. The intricate hydrogen bonding leads to the formation of a three dimensional network. PMID- 27006809 TI - Crystal structures of four indole derivatives with a phenyl substituent at the 2 position and a carbonyl group at the 3-position: the C(6) N-H?O chain remains the same, but the weak reinforcing inter-actions are different. AB - We describe the crystal structures of four indole derivatives with a phenyl ring at the 2-position and different carbonyl-linked substituents at the 3-position, namely 1-(2-phenyl-1H-indol-3-yl)ethanone, C16H13NO, (I), 2-cyclo-hexyl-1-(2 phenyl-1H-indol-3-yl)ethanone, C22H23NO, (II), 3,3-dimethyl-1-(2-phenyl-1H-indol 3-yl)butan-1-one, C20H21NO, (III), and 3-benzoyl-2-phenyl-1H-indole, C21H15NO, (IV). In each case, the carbonyl-group O atom lies close to the indole-ring plane and points towards the benzene ring. The dihedral angles between the indole ring system and 2-phenyl ring for these structures are clustered in a narrow range around 65 degrees . The dominant inter-molecular inter-action in each case is an N-H?O hydrogen bond, which generates a C(6) chain, although each structure possesses a different crystal symmetry. The C(6) chains are consolidated by different (C-H?O, C-H?pi and pi-pi stacking) weak inter-actions, with little consistency between the structures. PMID- 27006810 TI - Crystal structure of catena-poly[[[bis-(pyridine-4-carbo-thio-amide-kappaN (1))cadmium]-di-MU-thio-cyanato-kappa(2) N:S;kappa(2) S:N] methanol disolvate]. AB - The asymmetric unit of the polymeric title compound, {[Cd(NCS)2(C6H6N2S)].2CH3OH} n , consists of one cadmium(II) cation that is located on a centre of inversion as well as one thio-cyanate anion, one pyridine-4-carbo-thio-amide ligand and one methanol mol-ecule in general positions. The Cd(II) cations are octa-hedrally coordinated by the pyridine N atom of two pyridine-4-carbo-thio-amide ligands and by the S and N atoms of four thio-cyanate anions and are linked into chains along [010] by pairs of anionic ligands. These chains are further linked into layers extending along (201) by inter-molecular N-H?O and O-H?S hydrogen bonds. One of the amino H atoms of the pyridine-4-carbo-thio-amide ligand is hydrogen-bonded to the O atom of a methanol mol-ecule, and a symmetry-related methanol mol-ecule is the donor group to the S atom of another pyridine-4-carbo-thio-amide ligand whereby each of the pyridine-4-carbo-thio-amide ligands forms two pairs of centrosymmetric N-H?S and O-H?S hydrogen bonds. The methanol mol-ecules are equally disordered over two orientations. PMID- 27006808 TI - Crystal structure of fac-tricarbon-yl(cyclo-hexyl isocyanide-kappaC)(quinoline-2 carboxyl-ato-kappa(2) N,O)rhenium(I). AB - In the title compound, [Re(C10H6NO2)(C7H11N)(CO)3], the Re(I) atom is coordinated by three carbonyl ligands in a facial arrangement and by the N, O and C atoms from a chelating quinaldate anion and a monodentate isocyanide ligand, respectively. The resultant C4NO coordination sphere is distorted octa-hedral. A lengthening of the axial Re-CO bond trans to the isocyanide ligand is indicative of the trans effect. Individual complexes are stacked into rods parallel to [001] through displaced pi-pi inter-actions. Weak C-H?O hydrogen-bonding inter-actions between the rods lead to the formation of layers parallel to (010). These layers are stacked along [010] by C-H?H-C van der Waals contacts. PMID- 27006811 TI - Crystal structure of di-aqua-tris-(1-ethyl-1H-imidazole-kappaN (3))(sulfato kappaO)nickel(II). AB - In the title complex, [Ni(SO4)(C5H8N2)3(H2O)2], the Ni(II) ion is coordinated by three facial 1-ethyl-1H-imidazole ligands, one monodentate sulfate ligand and two water mol-ecules in a slightly distorted octa-hedral coordination environment. In the crystal, two pairs of O-H?O hydrogen bonds link complex mol-ecules, forming inversion dimers incorporating R 2 (4)(8), R 2 (2)(8) and R 2 (2)(12) rings. The dimeric unit also contains two symmetry-unique intra-molecular O-H?O hydrogen bonds. In addition, weak C-H?O hydrogen bonds, weak C-H?pi inter-actions and pi pi inter-actions with a centroid-centroid distance of 3.560 (2) A combine to form a three-dimensional network. One of the ethyl groups is disordered over two sets of sites with occupancies in the ratio 0.586 (7):0.414 (7). PMID- 27006812 TI - Crystal structure of 5-chloro-methyl-N-methyl-4-[(4-phenyl-1,2,3-triazol-1 yl)meth-yl]isoxazolidine-3-carboxamide. AB - The title compound, C15H18ClN5O2, crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. In both mol-ecules, the isoxazolidine rings have an envelope conformation with the O atoms at the flap positions. Each mol-ecule has three stereogenic centres with configurations 2(S), 3(S) and 4(R), confirmed by resonant scattering. Their conformations are significantly different, for example in mol-ecule A the phenyl ring is inclined to the triazole ring by 32.5 (2) degrees , while in mol-ecule B the corresponding dihedral angle is 10.7 (2) degrees . In the crystal, the A and B mol-ecules are linked via an N-H?O and a C H?O hydrogen bond. These units are linked by C-H?O and C-H?N hydrogen bonds, forming slabs parallel to the ab plane. There are C-H?pi inter-actions present within the slabs. PMID- 27006813 TI - Crystal structures of three anhydrous salts of the Lewis base 1,8-di-aza-bicyclo [5.4.0]undec-7-ene (DBU) with the ring-substituted benzoic acid analogues 4-amino benzoic acid, 3,5-di-nitro-benzoic acid and 3,5-di-nitro-salicylic acid. AB - The anhydrous salts of the Lewis base 1,8-di-aza-bicyclo-[5.4.0]undec-7-ene (DBU) with 4-amino-benzoic acid [1-aza-8-azoniabi-cyclo-[5.4.0]undec-7-ene 4-amino benzoate, C9H17N2 (+).C7H6NO2 (-) (I)], 3,5-di-nitro-benzoic acid [1-aza-8 azoniabi-cyclo-[5.4.0]undec-7-ene 3,5-di-nitro-benzoate, C9H17N2 (+).C7H3N2O6 ( ), (II)] and 3,5-di-nitro-salicylic acid (DNSA) [1-aza-8-azoniabi-cyclo [5.4.0]undec-7-ene 2-hy-droxy-3,5-di-nitro-benzoate, C9H17N2 (+).C7H3N2O7 (-), (III)] have been determined and their hydrogen-bonded structures are described. In both (II) and (III), the DBU cations have a common disorder in three of the C atoms of the six-membered ring moieties [site-occupancy factors (SOF) = 0.735 (3)/0.265 (3) and 0.686 (4)/0.314 (4), respectively], while in (III), there is additional rotational disorder in the DNSA anion, giving two sites (SOF = 0.72/0.28, values fixed) for the phenol group. In the crystals of (I) and (III), the cation-anion pairs are linked through a primary N-H?Ocarbox-yl hydrogen bond [2.665 (2) and 2.869 (3) A, respectively]. In (II), the ion pairs are linked through an asymmetric three-centre R 1 (2)(4), N-H?O,O' chelate association. In (I), structure extension is through amine N-H?Ocarbox-yl hydrogen bonds between the PABA anions, giving a three-dimensional structure. The crystal structures of (II) and (III) are very similar, the cation-anion pairs being associated only through weak C-H?O hydrogen bonds, giving in both overall two-dimensional layered structures lying parallel to (001). No pi-pi ring associations are present in any of the structures. PMID- 27006814 TI - Crystal structure of 5''-benzyl-idene-1'-methyl-4'-phenyl-tri-spiro-[ace-naphthyl ene-1,2'-pyrrolidine-3',1''-cyclo-hexane-3'',2'''-[1,3]dioxane]-2,6''-dione. AB - In the title compound, C36H31NO4, two spiro links connect the methyl-substituted pyrrolidine ring to the ace-naphthyl-ene and cyclo-hexa-none rings. The cyclo hexa-none ring is further connected to the dioxalane ring by a third spiro junction. The five-membered ring of the ace-naphthylen-1-one ring system adopts a flattened envelope conformation with the ketonic C atom as flap, whereas the dioxalane and pyrrolidine rings each have a twist conformation. The cyclo-hexa none ring assumes a boat conformation. Three intra-molecular C-H?O hydrogen bonds involving both ketonic O atoms as acceptors are present. In the crystal, C-H?O hydrogen bonds connect centrosymmetrically related mol-ecule into chains parallel to the b axis, forming rings of R 2 (2)(10)and R 2 (2)(8) graph-set motifs. PMID- 27006815 TI - A 2:1 co-crystal of 2-methyl-benzoic acid and N,N'-bis-(pyridin-4-ylmeth yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis. AB - The asymmetric unit of the title 2:1 co-crystal, 2C8H8O2.C14H14N4O2, comprises an acid mol-ecule in a general position and half a di-amide mol-ecule, the latter being located about a centre of inversion. In the acid, the carb-oxy-lic acid group is twisted out of the plane of the benzene ring to which it is attached [dihedral angle = 28.51 (8) degrees ] and the carbonyl O atom and methyl group lie approximately to the same side of the mol-ecule [hy-droxy-O-C-C-C(H) torsion angle = -27.92 (17) degrees ]. In the di-amide, the central C4N2O2 core is almost planar (r.m.s. deviation = 0.031 A), and the pyridyl rings are perpendicular, lying to either side of the central plane [central residue/pyridyl dihedral angle = 88.60 (5) degrees ]. In the mol-ecular packing, three-mol-ecule aggregates are formed via hy-droxy-O-H?N(pyrid-yl) hydrogen bonds. These are connected into a supra-molecular layer parallel to (12[Formula: see text]) via amide-N-H?O(carbon yl) hydrogen bonds, as well as methyl-ene-C-H?O(amide) inter-actions. Significant pi-pi inter-actions occur between benzene/benzene, pyrid-yl/benzene and pyrid yl/pyridyl rings within and between layers to consolidate the three-dimensional packing. PMID- 27006816 TI - Bis(benzyl-tri-methyl-ammonium) bis-[(4SR,12SR,18RS,26RS)-4,18,26-trihy-droxy-12 oxido-13,17-dioxahepta-cyclo [14.10.0.0(3,14).0(4,12).0(6,11).0(18,26).0(19,24)]hexa-cosa 1,3(14),6,8,10,15,19,21,23-nona-ene-5,25-dione] sesquihydrate: dimeric structure formation via [O-H-O](-) negative charge-assisted hydrogen bonds (-CAHB) with benzyl-tri-methyl-ammonium counter-ions. AB - The reaction between bis-ninhydrin resorcinol and benzyl-tri-methyl-ammonium fluoride in ethanol has produced the title compound, 2C10H16N(+).2C24H13O8 ( ).1.5H2O, which contains a unique centrosymmetric supra-molecular dimeric entity, where two deprotonated ligands are held together via two strong and short [O?O = 2.4395 (13) A] [O-H-O](-) bonds of the type negative charge-assisted hydrogen bonds (-CAHB). The central aromatic rings of the ligands create parallel displaced pi-pi stacking at an inter-planar distance of 3.381 (1) A, which helps stabilize the dimer. In the crystal, two symmetry-related solvent water mol ecules with a site occupancy of 0.75 are attached to the carbonyl groups of the dimer by weaker O-H?O hydrogen bonds, forming chains along [101]. PMID- 27006817 TI - Sodium dipotassium citrate, NaK2C6H5O7. AB - The crystal structure of sodium dipotassium citrate, Na(+).2K(+).C6H5O7 (3-), has been solved and refined using laboratory X-ray powder diffraction data, and optimized using density functional techniques. The Na(+) and one of the K(+) cations are six-coordinate, with bond-valence sums of 1.13 and 0.92 valence units, respectively, while another crystallographically independent K(+) cation is seven-coordinate with a bond-valence sum of 1.20. The [KO6] and [KO7] polyhedra share edges and corners to form layers perpendicular to the b axis. The distorted [NaO6] octa-hedra share edges to form chains along the a axis. The result is a three-dimensional network. The only O-H?O hydrogen bond is an intra molecular one between the hy-droxy group and a terminal carboxyl-ate group. PMID- 27006818 TI - Investigations of new potential photo-acid generators: crystal structures of 2 [(E)-2-phenyl-ethen-yl]phenol (ortho-rhom-bic polymorph) and (2E)-3-(2-bromo-phen yl)-2-phenyl-prop-2-enoic acid. AB - The title compounds, C14H12O, (I), and C15H11BrO2, (II), were prepared and characterized as part of our studies of potential new photo-acid generators. In (I), which crystallizes in the ortho-rhom-bic space group Pca21, compared to P21/n for the previously known monoclinic polymorph [Cornella & Martin (2013 ?). Org. Lett. 15, 6298-6301], the dihedral angle between the aromatic rings is 4.35 (6) degrees and the OH group is disordered over two sites in a 0.795 (3):0.205 (3) ratio. In the crystal of (I), mol-ecules are linked by O-H?pi inter-actions involving both the major and minor -OH disorder components, generating [001] chains as part of the herringbone packing motif. The asymmetric unit of (II) contains two mol-ecules with similar conformations (weighted r.m.s. overlay fit = 0.183 A). In the crystal of (II), both mol-ecules form carboxyl-ate inversion dimers linked by pairs of O-H?O hydrogen bonds, generating R 2 (2)(8) loops in each case. The dimers are linked by pairs of C-H?O hydrogen bonds to form [010] chains. PMID- 27006819 TI - New platinum(II) complexes with benzo-thia-zole ligands. AB - Four new platinum(II) complexes, namely tetra-ethyl-ammonium tri-bromido-(2 methyl-1,3-benzo-thia-zole-kappaN)platinate(II), [NEt4][PtBr3(C8H7NS)] (1), tetra ethyl-ammonium tri-bromido-(6-meth-oxy-2-methyl-1,3-benzo-thia-zole kappaN)platinate(II), [NEt4][PtBr3(C9H9NOS)] (2), tetra-ethyl-ammonium tri bromido-(2,5,6-trimethyl-1,3-benzo-thia-zole-kappaN)platinate(II), [NEt4][PtBr3(C10H11NS)] (3), and tetra-ethyl-ammonium tri-bromido-(2-methyl-5 nitro-1,3-benzo-thia-zole-kappaN)platinate(II), [NEt4][PtBr3(C8H6N2O2S)] (4), have been synthesized and structurally characterized by single-crystal X-ray diffraction techniques. These species are precursors of compounds with potential application in cancer chemotherapy. All four platinum(II) complexes adopt the expected square-planar coordination geometry, and the benzo-thia-zole ligand is engaged in bonding to the metal atom through the imine N atom (Pt-N). The Pt-N bond lengths are normal: 2.035 (5), 2.025 (4), 2.027 (5) and 2.041 (4) A for complexes 1, 2, 3 and 4, respectively. The benzo-thia-zole ligands are positioned out of the square plane, with dihedral angles ranging from 76.4 (4) to 88.1 (4) degrees . The NEt4 cation in 3 is disordered with 0.57/0.43 occupancies. PMID- 27006820 TI - Crystal structure of di-chlorido-bis-(dimethyl N-cyano-dithio-imino carbonate)zinc. AB - The Zn(II) atom in the title complex, [ZnCl2(C4H6N2S2)2], is coordinated in a distorted tetra-hedral manner by two Cl atoms and two terminal N atoms of two dimethyl N-cyano-dithio-imino-carbonate ligands. In the crystal, the complex mol ecules are connected through C-H?Cl hydrogen bonds and Cl?S contacts, leading to a two-dimensional structure extending parallel to the ab plane. PMID- 27006821 TI - Crystal structure of the salt bis-(tri-ethano-lamine-kappa(3) N,O,O')cobalt(II) bis-[2-(2-oxo-2,3-di-hydro-1,3-benzo-thia-zol-3-yl)acetate]. AB - The reaction of 2-(2-oxo-2,3-di-hydro-1,3-benzo-thia-zol-3-yl)acetic acid (NBTA) and tri-ethano-lamine (TEA) with Co(NO3)2 results in the formation of the title complex, [Co(C6H15NO3)2](C9H6NO3S)2, which is formed as a result of the association of bis-(tri-ethano-lamine)-cobalt(II) and 2-(2-oxo-2,3-di-hydro-1,3 benzo-thia-zol-3-yl)acetate units. It crystallizes in the monoclinic centrosymmetric space group P21/c, with the Co(II) ion situated on an inversion centre. In the complex cation, the Co(II) ion is octa-hedrally coordinated by two N,O,O'-tridentate TEA mol-ecules with a facial distribution and the N atoms in a trans arrangement. Two ethanol groups of each TEA mol-ecule form two five membered chelate rings around the Co(II) ion, while the third ethanol group does not coordinate to the metal. The free and coordinating hy-droxy groups of the TEA mol-ecules are involved in hydrogen bonding with the O atoms of NBTA anions, forming an infinite two-dimensional network extending parallel to the bc plane. PMID- 27006822 TI - Crystal structure of trans-di-chlorido-(1,4,8,11-tetra-aza-undecane-kappa(4) N)chromium(III) perchlorate determined from synchrotron data. AB - The structure of the title complex, [CrCl2(2,3,2-tet)]ClO4 (2,3,2-tet is 1,4,8,11 tetra-aza-undecane, C7H20N4), has been determined from synchrotron data. The Cr(III) ion is coordinated by the four N atoms of the 1,4,8,11-tetra-aza-undecane ligand in the equatorial plane and two chloride ions in an axial arrangement, displaying a slightly distorted octa-hedral coordination environment. The two H atoms of the secondary amines are grouped on the same side of the equatorial N4 plane (meso-RS conformation). The Cr-N bond lengths range from 2.069 (2) to 2.084 (2) A, while the mean Cr-Cl bond length is 2.325 (2) A. The crystal structure is stabilized by inter-molecular hydrogen-bonding inter-actions between the primary and secondary amine groups of the 2,3,2-tet ligands, the Cl ligands and the O atoms of the perchlorate counter-anion, forming corrugated layers parallel to (010). PMID- 27006823 TI - Impact of Severe Obesity and Weight Loss on Systolic Left Ventricular Function and Morphology: Assessment by 2-Dimensional Speckle-Tracking Echocardiography. AB - Obesity is associated with an increased risk of heart failure. Little is known about the impact of dietary changes on the cardiac sequelae in obese patients. Twenty-one obese subjects underwent a 12-week low calorie fasting phase of a formula diet. Transthoracic two-dimensional speckle-tracking echocardiography was performed to obtain systolic left ventricular strain before and after weight loss. Body mass index decreased significantly from 38.6 +/- 6.2 to 31.5 +/- 5.3 kg/m(2), and the total percentage fat loss was 19%. Weight reduction was associated with a reduction in blood pressure and heart rate. Left ventricular longitudinal global peak systolic strain was in the lower normal range (-18.7 +/- 3.2%) before weight loss and was unchanged (-18.8 +/- 2.4%) after 12 weeks on diet with substantial weight loss. Also, no significant change in global radial strain after weight loss was noted (41.1 +/- 22.0 versus 43.9 +/- 23.3, p = 0.09). Left atrial and ventricular dimensions were in normal range before fasting and remained unchanged after weight loss. In our study obesity was associated with normal systolic left ventricular function. A 12-week low calorie diet with successful weight loss can reduce blood pressure and heart rate. Systolic left ventricular function and morphology were not affected by rapid weight reduction. PMID- 27006825 TI - HIV-Associated Oral Mucosal Melanin Hyperpigmentation: A Clinical Study in a South African Population Sample. AB - Objective. The aim of the study was to determine the prevalence of HIV-associated oral mucosal melanin hyperpigmentation (HIV-OMH) in a specific population of HIV seropositive South Africans and to analyse the associations between HIV-OMH clinical features and the demographic and immunological characteristics of the study cohort. Material and Methods. This cross-sectional study included 200 HIV seropositive Black subjects. The collected data comprised age, gender, CD4+ T cell count, viral load, systemic disease, medications, oral site affected by HIV OMH, extent (localized or generalized), intensity of the pigmentation (dark or light), and smoking and snuff use. Results. Overall, 18.5% of the study cohort had HIV-OMH. Twenty-two and a half percent had OMH that could not with confidence be attributed to HIV infection, and 59% did not have any OMH. There was a significant but weak association between smoking and the presence of HIV-OMH. Conclusions. The prevalence of HIV-OMH in the study population was 18.5%, the gingiva being the most commonly affected site. It appears that the CD4+ T cell count does not play any role in the biopathology of HIV-OMH. PMID- 27006824 TI - Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery. AB - Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D) mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs) as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR) transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes. PMID- 27006826 TI - Identifying Prognostic Criteria for Survival after Resuscitation Assisted by Extracorporeal Membrane Oxygenation. AB - To improve survival rates during CPR, some patients are put on extracorporeal membrane oxygenation (ECMO). Among children who have undergone ECMO cardiopulmonary resuscitation (ECPR), the overall rate of survival to discharge is close to 40%. However, despite its wide acceptance and use, the appropriate indications and organizational requirements for ECPR have yet to be defined. Our objective was to assess the clinical outcomes of children after ECPR and to determine pre-ECPR prognostic factors for survival to guide its indication. Among the 19 patients who underwent ECPR between 2008 and 2014 in our center, 16 patients (84%, 95% confidence interval: 62-95%) died during their hospital stay, including nine (47%) who were on ECMO and seven (37%) after successful weaning from ECMO. All three survivors had normal cognitive status, but one child suffered from spastic quadriplegia. Survivors tended to have lower lactate, higher bicarbonate, and higher pH levels before ECMO initiation, as well as shorter length of resuscitation. In conclusion, in our center, ECPR has a poorer outcome than expected. Therefore, it might be important to identify, a priori, patients who might benefit from this treatment. PMID- 27006827 TI - Cerebral Hemispheric Lateralization Associated with Hippocampal Sclerosis May Affect Interictal Cardiovascular Autonomic Functions in Temporal Lobe Epilepsy. AB - It is well established that the temporal lobe epilepsy (TLE) is linked to the autonomic nervous system dysfunctions. Seizures alter the function of different systems such as the respiratory, cardiovascular, gastrointestinal, and urogenital systems. The aim of this work was to evaluate the possible factors which may be involved in interictal cardiovascular autonomic function in temporal lobe epilepsy with complex partial seizures, and with particular attention to hippocampal sclerosis. The study was conducted in 30 patients with intractable temporal lobe epilepsy (19 with left hippocampal sclerosis, 11 with right hippocampal sclerosis). All subjects underwent four tests of cardiac autonomic function: heart rate changes in response to deep breathing, heart rate, and blood pressure variations throughout resting activity and during hand grip, mental stress, and orthostatic tests. Our results show that the right cerebral hemisphere predominantly modulates sympathetic activity, while the left cerebral hemisphere mainly modulates parasympathetic activity, which mediated tachycardia and excessive bradycardia counterregulation, both of which might be involved as a mechanism of sudden unexpected death in epilepsy patients (SUDEP). PMID- 27006829 TI - The Association between Adult Participation and the Engagement of Preschoolers with ASD. AB - The ability for a child to engage in the classroom is associated with better academic outcomes. Yet, there is limited information on how child characteristics of autism and adult behavior impact engagement. This study examined (1) the pattern of adult participation and child engagement in preschool classrooms that serve children with ASD, (2) the associations between child engagement and adult participation, and (3) how characteristics of ASD (autism severity, language ability, and challenging behavior) moderate the relationship between adult participation and child engagement. Overall, children were less likely to be engaged when adults were actively or passively participating with them. Moderators impacted this relationship. Children with higher levels of autism severity were more likely to be engaged when adults were actively or passively participating with them. Similarly, children with lower language abilities were more likely to be engaged when adults were actively or passively participating with them. Finally, children with higher levels of challenging behaviors were less likely to be engaged when adults were actively or passively participating with them. These findings have important implications for how adults can best support the engagement of children with ASD. PMID- 27006828 TI - Prognostic Relevance of the Peritoneal Surface Disease Severity Score Compared to the Peritoneal Cancer Index for Colorectal Peritoneal Carcinomatosis. AB - BACKGROUND: Peritoneal Carcinomatosis Index (PCI) is a widely established scoring system that describes disease burden in isolated colorectal peritoneal carcinomatosis (CPC). Its significance may be diminished with complete cytoreduction. We explore the utility of the recently described Peritoneal Surface Disease Severity Score (PSDSS) and compare its prognostic value against PCI. METHODS: The endpoints were overall survival (OS), progression-free survival (PFS), and survival less than 18 months (18 MS). RESULTS: Fifty patients underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for CPC from 2003 to 2014, with 98% achieving complete cytoreduction. Median OS was 28.8 months (95% CI, 18.0-39.1); median PFS was 9.4 months (95% CI, 7.7-13.9). Univariate analysis showed that higher PCI was significantly associated with poorer OS (HR 1.11; 95% CI, 1.03-1.20) and PFS (HR 1.09; 95% CI, 1.03-1.14). Conversely, PSDSS was not associated with either endpoint. Multivariate analysis showed that PCI, but not PSDSS, was predictive of OS and PFS. PCI was also able to discriminate survival outcomes better than PSDSS for both OS and PFS. There was no association between 18 MS and either score. CONCLUSION: PCI is superior to PSDSS in predicting OS and PFS and remains the prognostic score of choice in CPC patients undergoing CRS/HIPEC. PMID- 27006830 TI - Morphologic and Clinical Outcome of Intracranial Aneurysms after Treatment Using Flow Diverter Devices: Mid-Term Follow-Up. AB - Flow diverters (FDs) are designed for the endovascular treatment of complex intracranial aneurysm configurations. From February 2009 to March 2013 28 patients (22 females, 6 males) were treated with FD; mean age was 57 years. Data, including aneurysm features, clinical presentation, history of previous bleeding, treatment, and follow-up results, are presented. Early postinterventional neurological deficits (transient: n = 3/enduring: n = 1) appeared in 4/28 patients (14%), and early improvement of neurological symptoms was observed in 7 patients with previous restriction of cranial nerve function. The overall occlusion rate was 20/26 (77%; 59% after 3 months). 77% achieved best results according to O'Kelly-Marotta score grade D with no contrast material filling (70% of those after 3 months). In 4/6 patients who did not achieve grade D, proximal and/or distal stent overlapping >=5 mm was not guaranteed sufficiently. During follow-up we did not detect any aneurysm recurrence or haemorrhage. In-stent stenosis emerged as the most frequent complication (4/27; 15%) followed by 2 cases of vascular obliteration (AICA/VA). In conclusion endovascular reconstruction using a FD represents a modern and effective treatment in those aneurysms that are not suitable for conventional interventional or surgical treatment. The appearance of severe complications was rare. PMID- 27006831 TI - Reproductive Pathological Changes Associated with Experimental Subchronic Corynebacterium pseudotuberculosis Infection in Nonpregnant Boer Does. AB - Corynebacterium pseudotuberculosis causes caseous lymphadenitis (CLA), which is a contagious and chronic disease in sheep and goats. In order to assess the histopathological changes observed in the reproductive organs of nonpregnant does infected with the bacteria, 20 apparently healthy adult Boer does were divided into four inoculation groups, intradermal, intranasal, oral, and control, consisting of five goats each. Excluding the control group, which was unexposed, other does were inoculated with 10(7) CFU/1 mL of live C. pseudotuberculosis through the various routes stated above. Thirty days after infection, the ovaries, uterus, and iliac lymph nodes were collected for bacterial recovery and molecular detection, as well as histopathological examination. The mean changes in necrosis, congestion, inflammatory cell infiltration, and oedema varied in severity among the ovaries, uterus, and iliac lymph nodes following different inoculation routes. Overall, the intranasal route of inoculation showed more severe (p < 0.05) lesions in all the organs examined. The findings of this study have shown that C. pseudotuberculosis could predispose to infertility resulting from pathological lesions in the uterus and ovaries of does. PMID- 27006832 TI - Chimerism Analysis of Cell-Free DNA in Patients Treated with Hematopoietic Stem Cell Transplantation May Predict Early Relapse in Patients with Hematologic Malignancies. AB - Background. We studied DNA chimerism in cell-free DNA (cfDNA) in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN) cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126) showed that, of 84 patients with 100% donor DNA in PMN, 16 (19%) had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19%) showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41%) showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse. PMID- 27006835 TI - Pulmonary Hypertension Secondary to Partial Anomalous Pulmonary Venous Return in an Elderly. AB - Background. Partial anomalous pulmonary venous return (PAPVR) is an uncommon congenital abnormality, which may present in the adult population. It is often associated with sinus venosus defect (SVD). The diagnosis and therapy for this condition may be challenging. Case Presentation. We describe a case of an elderly woman who presented with NYHA Class IV dyspnea and was suspected to have symptomatic pulmonary hypertension. She was later found to have anomalous right upper pulmonary vein return to the superior vena cava and associated SVD with bidirectional shunting. Therapeutic options were discussed and medical management alone with aggressive diuresis and sildenafil was adopted. Follow-up visits revealed success in the planned medical therapy. Conclusions. PAPVR is a rare congenital condition that may present during late adulthood. The initial predominant left-to-right shunting associated with this anomaly may go undetected for years with the gradual development of pulmonary hypertension and right heart failure due to right heart volume overload. Awareness of the condition is important, as therapy is time-sensitive with early detection potentially leading to surgical therapy as a viable option. PMID- 27006836 TI - Coronary Thrombosis without Dissection following Blunt Trauma. AB - Blunt trauma to the chest resulting in coronary thrombosis and ST elevation myocardial infarction (STEMI) is a rare but well-described occurrence in adults. Angiography in such cases has generally disclosed complete epicardial coronary occlusion with thrombus, indistinguishable from the findings commonly found in spontaneous plaque rupture due to atherosclerotic disease. In all previously reported cases in which coronary interrogation with intravascular ultrasound (IVUS) was performed in association with acute revascularization, coronary artery dissection was implicated as the etiology of coronary thrombosis. We present the first case report of blunt trauma-associated coronary thrombosis without underlying atherosclerosis or coronary dissection, as documented by IVUS imaging. PMID- 27006833 TI - Models to Tailor Brain Stimulation Therapies in Stroke. AB - A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke. PMID- 27006834 TI - Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain. AB - Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks. PMID- 27006837 TI - Early Recognition of Foreign Body Aspiration as the Cause of Cardiac Arrest. AB - Foreign body aspiration (FBA) is uncommon in the adult population but can be a life-threatening condition. Clinical manifestations vary according to the degree of airway obstruction, and, in some cases, making the correct diagnosis requires a high level of clinical suspicion combined with a detailed history and exam. Sudden cardiac arrest after FBA may occur secondary to asphyxiation. We present a 48-year-old male with no history of cardiac disease brought to the emergency department after an out-of-hospital cardiac arrest (OHCA). The patient was resuscitated after 15 minutes of cardiac arrest. He was initially managed with therapeutic hypothermia (TH). Subsequent history suggested FBA as a possible etiology of the cardiac arrest, and fiberoptic bronchoscopy demonstrated a piece of meat and bone lodged in the left main stem bronchus. The foreign body was removed with the bronchoscope and the patient clinically improved with full neurological recovery. Therapeutic hypothermia following cardiac arrest due to asphyxia has been reported to have high mortality and poor neurological outcomes. This case highlights the importance of early identification of FBA causing cardiac arrest, and we report a positive neurological outcome for postresuscitation therapeutic hypothermia following cardiac arrest due to asphyxia. PMID- 27006839 TI - Unilateral Absence of Mental Foramen with Surgical Exploration in a Living Human Subject. AB - The mental foramen (MF) is an important anatomic landmark of the mandible, in which the somatic afferent sensory nerve of the mandibular nerve emerges as mental nerve and blood vessels. The identification and actual location of MF are important in order to avoid sensory dysfunction or paresthesia due to mental nerve injury. In the literature there are some rare reports on the anatomical variations of the MF such as its location or presence of accessory foramina. The present report describes the absence of mental foramina on the left side of the mandible, as detected by cone-beam computed tomography before impacted tooth removal and observed directly during surgery. PMID- 27006838 TI - Adrenergic Inhibition with Dexmedetomidine to Treat Stress Cardiomyopathy during Alcohol Withdrawal: A Case Report and Literature Review. AB - Stress (Takotsubo) cardiomyopathy is a form of reversible left ventricular dysfunction with a heightened risk of ventricular arrhythmia thought to be caused by high circulating catecholamines. We report a case of stress cardiomyopathy that developed during severe alcohol withdrawal successfully treated with dexmedetomidine. The case involves a 53-year-old man with a significant history of alcohol abuse who presented to a teaching hospital with new-onset seizures. His symptoms of acute alcohol withdrawal were initially treated with benzodiazepines, but the patient later developed hypotension, and stress cardiomyopathy was suspected based on ECG and echocardiographic findings. Adjunctive treatment with the alpha-2-adrenergic agonist, dexmedetomidine, was initiated to curtail excessive sympathetic outflow of the withdrawal syndrome, thereby targeting the presumed pathophysiology of the cardiomyopathy. Significant clinical improvement was observed within one day of initiation of dexmedetomidine. These findings are consistent with other reports suggesting that sympathetic dysregulation during alcohol withdrawal produces ideal pathobiology for stress cardiomyopathy and leads to ventricular arrhythmogenicity. Stress cardiomyopathy should be recognized as a complication of alcohol withdrawal that significantly increases cardiac-related mortality. By helping to correct autonomic dysregulation of the withdrawal syndrome, dexmedetomidine may be useful in the treatment of stress-induced cardiomyopathy. PMID- 27006840 TI - Neisseria lactamica Causing a Lung Cavity and Skin Rash in a Renal Transplant Patient: First Report from India. AB - Neisseria lactamica, a commensal, has been very rarely reported to cause diseases in immunocompromised hosts. In medical literature, there is only one report of a cavitatory lung lesion caused by it. The patient was a kidney transplant recipient. Neisseria lactamica was found to be the cause of his pulmonary cavity and a desquamating rash on feet. With the rapidly spreading medical advance, more and more patients are getting organ transplants, so the population of immunocompromised people is on the rise. We expect more sinister and less expected organisms to cause diseases in patients who have organ transplants. PMID- 27006841 TI - Polymicrobial Pituitary Abscess Predominately Involving Escherichia coli in the Setting of an Apoplectic Pituitary Prolactinoma. AB - Pituitary abscess is a rare intracranial infection that can be life-threatening if not appropriately diagnosed and treated upon presentation. The most common presenting symptoms include headache, anterior pituitary hypofunction, and visual field disturbances. Brain imaging with either computed tomography or magnetic resonance imaging usually reveals intra- or suprasellar lesion(s). Diagnosis is typically confirmed intra- or postoperatively when pathological analysis is done. Clinicians should immediately start empiric antibiotics and request a neurosurgical consult when pituitary abscess is suspected. Escherichia coli (E. coli) causing intracranial infections are not well understood and are uncommon in adults. We present an interesting case of an immunocompetent male with a history of hypogonadism presenting with worsening headache and acute right eye vision loss. He was found to have a polymicrobial pituitary abscess predominantly involving E. coli in addition to Actinomyces odontolyticus and Prevotella melaninogenica in the setting of an apoplectic pituitary prolactinoma. The definitive etiology of this infection was not determined but an odontogenic process was suspected. A chronic third molar eruption and impaction in close proximity to the pituitary gland likely led to contiguous spread of opportunistic oral microorganisms allowing for a polymicrobial pituitary abscess formation. PMID- 27006843 TI - Multidrug-Resistant Tuberculosis during Pregnancy: Two Case Reports and Review of the Literature. AB - Multidrug-resistant tuberculosis (MDR-TB) is identified from the time of introduction of antituberculosis treatment and is a known worldwide public health crisis affecting women of reproductive age group. Management issues raised by pregnant women with MDR tuberculosis are challenging due to the limited clinical experience available with the use of second line drugs. We hereby report two cases of MDR-TB during pregnancy: one patient was on second line drugs, while another one was evaluated and diagnosed to have MDR-TB in last trimester. At 6 months of follow-up both mothers and babies are doing well. The approach to such cases along with review of the literature is discussed. PMID- 27006842 TI - Bile Nephropathy in Flucloxacillin-Induced Cholestatic Liver Dysfunction. AB - Kidney injury in the context of cholestatic liver dysfunction is not uncommon; this has been historically referred to as cholemic nephrosis implying a direct deleterious renal effect of cholemia. However, scepticism about the exact role that bile and its constituents play in this injury has led to the disappearance of the term. We describe a case of severe AKI due to bile nephropathy with bile casts in flucloxacillin-induced liver dysfunction. We also discuss the recent literature reviving the concept of bile nephropathy. PMID- 27006844 TI - A Case of Thanatophoric Dysplasia Type I with Fetal Hydrops in the First Trimester. AB - During a routine prenatal exam, a 36-year-old female in her third pregnancy was diagnosed with fetal hydrops at 11 weeks of gestation. The pregnancy was monitored with periodic ultrasounds; however, spontaneous resolution was not observed. Amniotic fluid examination at 16 weeks of gestation showed a normal karyotype; however, macrocephaly, a narrow thorax, and shortening of the long bones were observed on ultrasonography. With the strong suspicion of a fetal skeletal disease, specifically thanatophoric dysplasia (TD), and after extensive genetic counseling, termination of the pregnancy was performed per the parents' wishes with mechanical cervical dilation and gemeprost (PGE1) administration. Following delivery, the fetus was found to have macrocephaly, a narrow bell shaped thorax, and a protuberant abdomen, as well as curved long bones, H-shaped platyspondyly, and curved clavicles on skeletal radiography. As a result, the fetus was diagnosed with TD type I. This case illustrates that although TD is a rare disease, an accurate prenatal diagnosis can be made with the use of ultrasonography. PMID- 27006845 TI - Diffuse Venous Malformation of the Uterus in a Pregnant Woman with Klippel Trenaunay Syndrome Diagnosed by DCE-MRI. AB - Background. We experienced a rare case of a pregnant woman with Klippel-Trenaunay syndrome complicated with diffuse venous malformation of the uterus. This is the first report on the usefulness of dynamic contrast-enhanced-MRI for the diagnosis of diffuse venous malformation of the uterus. Case Presentation. A 23-year-old woman presented with convulsions and talipes equinus position of both lower limbs at 11 weeks of gestation. At 27 weeks, ultrasonography demonstrated tubular echolucent spaces throughout the myometrium. Dynamic MRI at 37 weeks revealed that the myometrial lesion was enhanced slowly and showed homogeneous enhancement even on a 10 min delayed image. Taken together with unilateral foot hypertrophy, varices, and port-wine stain, the patient was diagnosed as having Klippel Trenaunay syndrome complicated with diffuse venous malformation of the pregnant uterus. The patient underwent elective cesarean section because of severe dystonia. The lower uterine segment was thickened and heavy venous blood flow was observed at the incision. Histological diagnosis of the myometrial biopsy specimen was venous malformation. Conclusions. Both diffuse venous malformation and Klippel-Trenaunay syndrome during pregnancy can involve considerable complications, in particular, massive bleeding during labor. Women who suffer from this syndrome should be advised about the risk of complications of pregnancy. PMID- 27006846 TI - Lesser Trochanter Migration following Intramedullary Fixation of an Intertrochanteric Femur Fracture. AB - Intertrochanteric femur fractures are commonly observed in the elderly and may be associated with a complete fracture of the lesser trochanter in over 50% of cases. The migration of the lesser trochanter secondary to the psoas muscle contracture is a rare event. This case report presents a rare case of sudden groin pain three-week status after intramedullary fixation of a intertrochanteric femur fracture. PMID- 27006847 TI - Urinary Bladder Adenocarcinoma Metastatic to the Abdominal Wall: Report of a Case with Cytohistologic Correlation. AB - We report a case of adenocarcinoma metastatic to the abdominal wall in a 71-year old man with a history of primary bladder adenocarcinoma. CT-guided core biopsy was performed; imprints and histologic sections showed malignant glands lined by tumor cells with hyperchromatic nuclei and prominent nucleoli, infiltrating through skeletal muscle. Immunohistochemistry revealed positivity for CK7, membranous/cytoplasmic beta-catenin, caudal-type homeobox transcription factor 2 (CDX2), and alpha-methylacyl coenzyme A racemase and negativity for CK20, p63, prostate-specific antigen (PSA), and prostate-specific acid phosphatase (PSAP). These findings were interpreted as metastatic adenocarcinoma, consistent with bladder primary. Primary bladder adenocarcinoma is a rare malignancy arising within glandular metaplasia and is associated with cystitis cystica and cystitis glandularis. Predisposing factors include bladder exstrophy, schistosomiasis, and other causes of chronic bladder irritation. This tumor is divided into intestinal, clear cell, and signet ring cell subtypes. Treatment involves radical cystectomy with pelvic lymph node dissection, and prognosis is unfavorable. Primary bladder adenocarcinoma should be differentiated from urachal adenocarcinoma, which arises from urachal remnants near the bladder dome, and secondary adenocarcinoma, or vesical involvement by adenocarcinoma from a different primary. CK7, CK20, CDX2, thrombomodulin, and beta-catenin can help distinguish primary bladder adenocarcinoma from colonic adenocarcinoma; PSA and PSAP can help distinguish primary bladder adenocarcinoma from prostate adenocarcinoma. PMID- 27006848 TI - Unexplained Neonatal Cardiorespiratory Collapse at Five Minutes of Age. AB - We report a case in which a term neonate suffered cardiorespiratory collapse at five minutes of age following an uncomplicated delivery and Apgar score of eight at one minute. Following prolonged cardiopulmonary resuscitation, the infant recovered well with no neurological deficit. Although sudden and unexpected postnatal collapse has been extensively described, this case does not fulfil its definition criteria. It provides a diagnostic challenge for clinicians and to the best of our knowledge is the first report of unexplained cardiorespiratory collapse at five minutes of age. The case serves as a timely reminder that cord gas analysis is recommended in all cases of potential fetal compromise and that Apgar scores should be used with caution as a predictor of neurological sequelae. PMID- 27006849 TI - US and CT of the Liver after Electric Shock. AB - Liver injuries caused by high voltage electricity are rare and result in high mortality and morbidity. They are produced by the resistance to the passage of electrical current through the tissue, which creates heat that leads to coagulation necrosis and rupture of the cell membrane. We present a case of an electrical injury to the liver, diagnosed by ultrasound and CT in a 39-year-old man who presented with skin burns on his right hand and right hemiabdomen. Injuries occurred after the contact with 220 kV high voltage electricity. PMID- 27006850 TI - ANA Negative Systemic Lupus Erythematosus Leading to CTEPH, TTP-Like Thrombocytopenia, and Skin Ulcers. AB - SLE affects almost every organ system, with differing degrees of severity. During its clinical course periods of flares may alternate with periods of remission culminating in disease and therapy related damage. We describe a case of ANA negative SLE with severe thrombocytopenia, cutaneous vasculitis, antiphospholipid antibody syndrome, and pulmonary artery hypertension. As there is no definitive cure for SLE the treatment lies in caring for the individual organ systems involved and simultaneously taking care of the patient as a whole. PMID- 27006851 TI - A Case of Rituximab Use as an Induction and Maintenance of Remission in ANCA Associated Vasculitis. AB - Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is a multisystem autoimmune disease affecting mainly microscopic blood vessels due to circulating autoantibodies against neutrophil cytoplasmic antigens. We report a case of a 57-year-old female patient presenting with hemoptysis, sinusitis, and conjunctivitis. Based on lung biopsy, the diagnosis of antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) was established. She was put on rituximab as induction and maintenance therapy. She responded initially to rituximab as induction therapy but failed to respond in the maintenance course of the drug. Rituximab was stopped and mycophenolate mofetil was administered. She responded as laboratory c-ANCA titers turned negative and symptoms subsided. There are no randomized clinical trials addressing rituximab effect in induction and remission at the same time. This case report doubts the efficacy of the use of rituximab therapy for both induction and maintenance of remission at the same time, waiting for the results of the ongoing trials. PMID- 27006852 TI - Uncommon Caecum Diverticulitis Mimicking Acute Appendicitis. AB - Diverticulum of the cecum is a rarely seen reason of acute abdomen and it is difficult to be distinguished from appendicitis. The diagnosis is generally made during operation. We have presented this case in order to remember that it is a disease which should be kept in mind in cases of right lower quadrant pain. PMID- 27006853 TI - Management of a Septic Open Abdomen Patient with Spontaneous Jejunal Perforation after Emergent C/S with Confounding Factor of Mild Acute Pancreatitis. AB - Introduction. We report the management of a septic Open Abdomen (OA) patient by the help of negative pressure therapy (NPT) and abdominal reapproximation anchor (ABRA) system in pregnant woman with spontaneous jejunal perforation after emergent cesarean section (C/S) with confounding factor of mild acute pancreatitis (AP). Presentation of Case. A 29-year-old and 34-week pregnant woman with AP underwent C/S. She was arrested after anesthesia induction and responded to cardiopulmonary resuscitation (CPR). There were only ash-colored serosanguinous fluid within abdomen during C/S. After C/S, she was transferred to intensive care unit (ICU) with vasopressor support. On postoperative 1st day, she underwent reoperation due to fecal fluid coming near the drainage. Leakage point could not be identified exactly and operation had to be deliberately abbreviated due to hemodynamic instability. NPT was applied. Two days later source control was provided by conversion of enteroatmospheric fistula (EAF) to jejunostomy. ABRA was added and OA was closed. No hernia developed at 10-month follow-up period. Conclusion. NPT application in septic OA patient may gain time to patient until adequate source control could be achieved. Using ABRA in conjunction with NPT increases the fascial closure rate in infected OA patient. PMID- 27006854 TI - Tendency to Ingest Foreign Bodies in Mentally Retarded Patients: A Case with Ileal Perforation Caused by the Ingestion of a Teaspoon. AB - Introduction. Unintentional foreign body ingestion commonly occurs accidentally in children aged between 3 months and 6 years and at advanced ages or results from psychiatric disorders such as hallucination in patients with mental retardation. Most of the ingested foreign bodies are naturally discharged from the body but some of them may require surgical intervention. Presentation of Case. A 29-year-old mentally retarded female patient was admitted to the emergency service with a two-day history of abdominal pain, nausea, and vomiting. Physical examination revealed abdominal tenderness, defense, and rebound on palpation. Radiological examination revealed diffuse air-fluid levels and a radiopaque impression of a metal object in the right upper quadrant. The metal teaspoon causing ileal perforation was extracted by emergency laparotomy. On postoperative day 7, the patient was uneventfully discharged following a psychiatric consultation. Discussion. Foreign body ingestion can occur intentionally in children at developing ages and old-age patients, or adults and prisoners, whereas it may occur unintentionally in patients with mental retardation due to hallucination. However, repeated foreign body ingestion is very rare in individuals other than mentally retarded patients. Conclusion. Mentally retarded patients should be kept under close surveillance by surgeons and psychiatrists due to their tendency to ingest foreign bodies. PMID- 27006855 TI - Intravesical Botulinum Toxin for Persistent Autonomic Dysreflexia in a Pediatric Patient. AB - Introduction. We present a novel case of persistent autonomic dysreflexia in a pediatric spinal cord injury patient treated successfully with intravesical botulinum toxin. Study Design. A retrospective chart review of one patient seen at the Children's Hospital of Wisconsin from 2006 to 2012 was performed. Results. A pediatric spinal cord injury patient with known neurogenic bladder presented with severe hypertension consistent with autonomic dysreflexia. His symptoms and hypertension did not improve with conservative measures, and he necessitated ICU admission and antihypertensive drips. He was taken to the operating room for intravesical botulinum toxin for refractory bladder spasms. Following this, his symptoms abated, and he was weaned off IV antihypertensives and returned to his baseline state. His symptoms were improved for greater than six months. Conclusions. There are few treatment options for the management of refractory autonomic dysreflexia. Intravesical botulinum toxin has never been reported for this use. Dedicated research is warranted to assess its efficacy, as it was used successfully to abort autonomic dysreflexia in this patient. PMID- 27006856 TI - Epidemiology of Substance Use among University Students in Sudan. AB - Background. Youth populations are vulnerable to substance use particularly in developing countries where circumstances may be favorable for it. There is no published data on substance use among the youth in Sudan other than on tobacco use. Objectives. The aim of this study was to investigate the prevalence, circumstances, and factors associated with substance use. Methods. An institution based survey was conducted on a sample of 500 students. Data was collected using a questionnaire designed by the WHO for student drug surveys and analyzed using IBM SPSS version 20. Results. The overall prevalence of substance use is 31%. The current prevalence of tobacco, cannabis, alcohol, amphetamines, tranquilizers, inhalants, opiates, cocaine, and heroin use was 13.7%, 4.9%, 2.7%, 2.4%, 3.2%, 1%, 1.2%, 0.7%, and 0.5%, respectively. Curiosity (33.1%) was the main reason for initiation of substance use. The main adverse effects reported were health problems (19.7%) and theft (19.7%). Peers (40.9%) were the prime source of substance use. On multivariate analysis, male sex was the principle predictor for substance use (AOR: 5.55; 95% CI: 3.38, 9.17). Conclusion. Strategies to control substance use should encompass the role of the university and parents in observing and providing education to improve awareness of substances and their consequences. PMID- 27006857 TI - Safety and Effectiveness of Total Thyroidectomy and Its Comparison with Subtotal Thyroidectomy and Other Thyroid Surgeries: A Systematic Review. AB - Diseases associated with the thyroid gland are one of the most frequently seen endocrine disorders across the globe. Total thyroidectomy is currently the preferred treatment for many thyroid diseases. Controversies exist among surgeons regarding safety of total thyroidectomy due to the risk associated with it like postoperative hypoparathyroidism or recurrent laryngeal nerve damage. Since, in the recent years, the incidence of thyroidectomy is in increasing trend in south Indian population, this review aims to study the available data regarding the appropriateness and safety of total thyroidectomy and compares it with subtotal thyroidectomy and other thyroid surgeries. This is a retrospective comprehensive review of various articles and publications regarding total and partial thyroidectomy performed across the world. Many retrospective studies and few prospective studies suggest that the incidence of transient hypocalcemia is higher after total thyroidectomy than after subtotal thyroidectomy, but the incidence of other complications including recurrent laryngeal nerve palsy and postoperative hematoma is not significantly different between the two procedures. Hence in our review we found that total thyroidectomy is safe and cost effective with low complication rates and provides little significant advantage of being safer procedure compared to subtotal thyroidectomy. PMID- 27006858 TI - Freezing of Gait in Parkinson's Disease Is Associated with Reduced 6 [(18)F]Fluoro-l-m-tyrosine Uptake in the Locus Coeruleus. AB - Freezing of gait (FOG) is a common disorder in Parkinson's disease (PD) and could be attributed to a reduction in brain noradrenaline. The aim of this study was to determine the relationship between aromatic l-amino acid decarboxylase (AADC) activity in the locus coeruleus (LC) and FOG in PD using high-resolution positron emission tomography with an AADC tracer, 6-[(18)F]fluoro-l-m-tyrosine (FMT). We assessed 40 patients with PD and 11 age-matched healthy individuals. PD was diagnosed based on the UK Brain Bank criteria by two movement disorder experts. FOG was directly observed by the clinician and assessed using a patient questionnaire. FMT uptake in the LC, caudate, and putamen was analyzed using PMOD software on coregistered magnetic resonance images. FOG was present in 30 patients. The severity of FOG correlated with the decrease of FMT uptake in the LC regardless of disease duration and the severity of other motor impairments, indicating dysfunction of the noradrenergic network in FOG. PMID- 27006859 TI - The Use of Fetal Noninvasive Electrocardiography. AB - Preeclampsia (PE) is one of the severe complications of pregnancy that leads to fetal deterioration. The aim was to survey the validity of fetal distress diagnostics in case of Doppler ultrasonic umbilical vein and arteries blood flow velocity investigation and ECG parameters analysis obtained from maternal abdominal signal before labor in preeclamptic patients. Fetal noninvasive ECG and umbilical arterial and venous Doppler investigation were performed in 120 patients at 34-40 weeks of gestation. And 30 of them had physiological gestation and were involved in Group I. In Group II 52 pregnant women with mild-moderate PE were observed. 38 patients with severe PE were monitored in Group III. The most considerable negative correlation was determined in pair Apgar score 1 versus T/QRS (R = -0.50; p < 0.05). So the increased T/QRS ratio was the most evident marker of fetal distress. Fetal noninvasive ECG showed sensitivity of 96.6% and specificity of 98.4% and, therefore, was determined as more accurate method for fetal monitoring. PMID- 27006860 TI - Extraocular Muscles Tension, Tonus, and Proprioception in Infantile Strabismus: Role of the Oculomotor System in the Pathogenesis of Infantile Strabismus-Review of the Literature. AB - The role played by the extraocular muscles (EOMs) in the etiology of concomitant infantile strabismus is still debated and it has not yet definitively established if the sensory anomalies in concomitant strabismus are a consequence or a primary cause of the deviation. The commonest theory supposes that most strabismus results from abnormal innervation of the EOMs, but the cause of this dysfunction and its origin, whether central or peripheral, are still unknown. The interaction between sensory factors and innervational factors, that is, esotonus, accommodation, convergence, divergence, and vestibular reflexes in visually immature infants with family predisposition, is suspected to create conditions that prevent binocular alignment from stabilizing and strengthening. Some role in the onset of fixation instability and infantile strabismus could be played by the feedback control of eye movements and by dysfunction of eye muscle proprioception during the critical period of development of the visual sensory system. A possible role in the onset, maintenance, or worsening of the deviation of abnormalities of muscle force which have their clinical equivalent in eye muscle overaction and underaction has been investigated under either isometric or isotonic conditions, and in essence no significant anomalies of muscle force have been found in concomitant strabismus. PMID- 27006861 TI - The Effect of Ethnic Variation on the Success of Induced Labour in Nulliparous Women with Postdates Pregnancies. AB - Objective. To identify the potential effect of ethnic variation on the success of induction of labour in nulliparous women with postdates pregnancies. Study Design. This was an observational cohort study of women being induced for postdates pregnancies (>=41 weeks) between 2007 and 2013. Women induced for stillbirths and with multiple pregnancies were excluded. The primary objective was to identify the effect of ethnicity on the caesarean section (CS) delivery rates in this cohort of women. Results. 1,636 nulliparous women were identified with a mean age of 27.2 years. 95.8% of the women were of White ethnic origin, 2.6% were Asian, and 1.6% were of Black ethnic origin. The CS delivery rate was 24.4% in the total sample. Women of Black ethnic origin had a 3.26 times greater likelihood for CS in comparison to White women, after adjusting for maternal age, BMI, smoking, presence of meconium, use of epidural analgesia, fetal gender, birth weight, and head circumference (adjusted OR = 3.26; 95% CI: 1.31-8.08, p = 0.011). Conclusion. We have found that nulliparous women of Black ethnicity demonstrate an almost threefold increased risk of caesarean section delivery when induced for postdates pregnancy. PMID- 27006862 TI - Does Hamulotomy during Palatoplasty Have Any Effect on Hearing Ability in Nonsyndromic Cleft Palate Patients? A Prospective, Single Blind, Comparative Study. AB - The primary goal of palatoplasty is to achieve a tension-free palatal closure ensuring no postoperative complications. Many surgeons fracture the pterygoid hamulus to minimize tension during palatoplasty. However, this maneuver gained criticism by some authors on the grounds that it may lead to Eustachian Tube dysfunction. Our study intended to figure out the relationship of hamulus fracture with the postoperative state of middle ear in cleft palate children. Fifty consecutive cleft palate patients with an age range of 10 months to 5 years were recruited. All the patients were assigned to either hamulotomy or nonhamulotomy group preoperatively. The patients were subjected to otoscopic examination and auditory function evaluation by brainstem evoked response audiometry (BERA) preoperatively and 1 month and 6 months postoperatively. Otoscopy revealed that the difference in the improvement of middle ear status in both groups was statistically insignificant. Moreover, there was no significant difference in the BERA outcomes of the fracture and nonfracture populations. Complication rate in both groups was also statistically not significant. It can be concluded that hamulotomy does not have any effect on the hearing ability in cleft palate population, so hamulotomy can be performed for tension-free closure during palatoplasty. PMID- 27006863 TI - Once the rockets are up, who should care where they come down? The problem of responsibility ascription for the negative consequences of biofuel innovations. AB - Responsible Innovation (RI) is often heralded in EU policy circles as a means to achieve ethically acceptable, sustainable innovations. Yet, conceptual questions on the specific notion of 'responsibility' and to what extent an innovation can be 'responsible' are only partly addressed. In this chapter the question of responsibility for the indirect negative effects of biofuel innovations is explored. While initially hailed as one of the much needed solutions in the global struggle against climate change, the use of biofuels has become increasingly criticised. It is argued that the increased production of biofuels has put smallholder farmers out of business, has given rise to increased food prices, sparking food riots in several countries, while also contributing to further environmental degradation as the demand for new biofuels requires the development of new croplands at the cost of forests and peat lands. In the current market-based system it is customary to disburden researchers and business companies from any responsibility for the more remote consequences of their actions. When harmful consequences are brought about through the mediation of (perhaps a long series of) market transactions, they are often considered inevitable and excusable and not an appropriate occasion for invoking anybody's responsibility. But how broad is the scope of responsibility when it comes to the above mentioned social and ecological problems? By invoking the sacred duty to "innovate", the business company could perhaps be exculpated. In our age, innovation is often so much celebrated that many negative impacts are duly accepted as the inevitable price of progress. By approaching responsibility from a perspective that takes into account the economic and ecological interconnectedness of the world, we show how the debate on Responsible Innovation in biofuels becomes tied in with global debates on economic justice and bioscarcity. In conclusion we argue that if we-assuming this interconnectedness take the current requirements of "Responsible" Innovation seriously, it would result in a demanding practice that calls for a substantial departure from business as usual, which prompts the question to what extent it is reasonable to incorporate what are actually demands for global justice in programs for innovation. PMID- 27006864 TI - Occurrence of shale soils along the Calabar-Itu highway, Southeastern Nigeria and their implication for the subgrade construction. AB - This study concerned a stretch of 17 km of a 94-km highway alignment in Southeastern Nigeria that has a high incidence of pavement failure arising from subgrade failure. The subgrade of this section of the roadway is composed of Ekenkpon shale, New Netim marl, and Nkporo shale. Under the Unified Soil Classification System, the shales classify as OH (organic clay) and the marl classifies as MH (inorganic silt). Under the American Association of State and Transportation Officials (AASHTO) M 145 soil classification, all these soils classify as A-7-5 soil. Using the AASHTO M 145 group index, none of these soils was considered suitable as subgrade in its native form. Therefore, cement was investigated as a stabilizing agent. Testing demonstrated that 7, 3 and 12 % by weight were the optimum cement contents to reinforce the Ekenkpon shale, New Netim marl, and Nkporo shale, respectively. PMID- 27006865 TI - Estimation of the contribution of exports to the provincial economy: an analysis based on China's multi-regional input-output tables. AB - This paper developed an estimation model for the contribution of exports to a country's regional economy based on the Chenery-Moses model and conducted an empirical analysis using China's multi-regional input-output tables for 1997, 2002, and 2007. The results indicated that China's national exports make significantly different contributions to the provincial economy in various regions, with the greatest contribution being observed in the eastern region and the smallest in the central region. The provinces are also subjected to significantly different export spillover effects. The boosting effect for the eastern provinces is primarily generated from local exports, whereas the western provinces primarily benefit from the export spillover effect from the eastern provinces. The eastern provinces, such as Guangdong, Zhejiang, Jiangsu, and Shanghai, are the primary sources of export spillover effects, and Guangdong is the largest source of export spillover effects for almost all of the provinces in China. PMID- 27006866 TI - Common coupled fixed point theorems satisfying rational type contractive conditions in b-metric spaces. AB - In this article, existence and uniqueness of common coupled fixed point for a pair of mappings in the setup of complete b-metric spaces are studied. The derived result generalizes and extends some well known results from the existing literature in b-metric spaces. Appropriate example is also given. PMID- 27006867 TI - The economic status of older people's households in urban and rural settings in Peru, Mexico and China: a 10/66 INDEP study cross-sectional survey. AB - Few data are available from middle income countries regarding economic circumstances of households in which older people live. Many such settings have experienced rapid demographic, social and economic change, alongside increasing pension coverage. Population-based household surveys in rural and urban catchment areas in Peru, Mexico and China. Participating households were selected from all households with older residents. Descriptive analyses were weighted back for sampling fractions and non-response. Household income and consumption were estimated from a household key informant interview. 877 Household interviews (3177 residents). Response rate 68 %. Household income and consumption correlated plausibly with other economic wellbeing indicators. Household Incomes varied considerably within and between sites. While multigenerational households were the norm, older resident's incomes accounted for a high proportion of household income, and older people were particularly likely to pool income. Differences in the coverage and value of pensions were a major source of variation in household income among sites. There was a small, consistent inverse association between household pension income and labour force participation of younger adult co residents. The effect of pension income on older adults' labour force participation was less clear-cut. Historical linkage of social protection to formal employment may have contributed to profound late-life socioeconomic inequalities. Strategies to formalise the informal economy, alongside increases in the coverage and value of non-contributory pensions and transfers would help to address this problem. PMID- 27006868 TI - Bringing computational science to the public. AB - BACKGROUND: The increasing use of computers in science allows for the scientific analyses of large datasets at an increasing pace. We provided examples and interactive demonstrations at Dundee Science Centre as part of the 2015 Women in Science festival, to present aspects of computational science to the general public. We used low-cost Raspberry Pi computers to provide hands on experience in computer programming and demonstrated the application of computers to biology. Computer games were used as a means to introduce computers to younger visitors. The success of the event was evaluated by voluntary feedback forms completed by visitors, in conjunction with our own self-evaluation. This work builds on the original work of the 4273pi bioinformatics education program of Barker et al. (2013, BMC Bioinform. 14:243). 4273pi provides open source education materials in bioinformatics. This work looks at the potential to adapt similar materials for public engagement events. RESULTS: It appears, at least in our small sample of visitors (n = 13), that basic computational science can be conveyed to people of all ages by means of interactive demonstrations. Children as young as five were able to successfully edit simple computer programs with supervision. This was, in many cases, their first experience of computer programming. The feedback is predominantly positive, showing strong support for improving computational science education, but also included suggestions for improvement. CONCLUSIONS: Our conclusions are necessarily preliminary. However, feedback forms suggest methods were generally well received among the participants; "Easy to follow. Clear explanation" and "Very easy. Demonstrators were very informative." Our event, held at a local Science Centre in Dundee, demonstrates that computer games and programming activities suitable for young children can be performed alongside a more specialised and applied introduction to computational science for older visitors. PMID- 27006870 TI - Comparing writing style feature-based classification methods for estimating user reputations in social media. AB - In recent years, the anonymous nature of the Internet has made it difficult to detect manipulated user reputations in social media, as well as to ensure the qualities of users and their posts. To deal with this, this study designs and examines an automatic approach that adopts writing style features to estimate user reputations in social media. Under varying ways of defining Good and Bad classes of user reputations based on the collected data, it evaluates the classification performance of the state-of-art methods: four writing style features, i.e. lexical, syntactic, structural, and content-specific, and eight classification techniques, i.e. four base learners-C4.5, Neural Network (NN), Support Vector Machine (SVM), and Naive Bayes (NB)-and four Random Subspace (RS) ensemble methods based on the four base learners. When South Korea's Web forum, Daum Agora, was selected as a test bed, the experimental results show that the configuration of the full feature set containing content-specific features and RS SVM combining RS and SVM gives the best accuracy for classification if the test bed poster reputations are segmented strictly into Good and Bad classes by portfolio approach. Pairwise t tests on accuracy confirm two expectations coming from the literature reviews: first, the feature set adding content-specific features outperform the others; second, ensemble learning methods are more viable than base learners. Moreover, among the four ways on defining the classes of user reputations, i.e. like, dislike, sum, and portfolio, the results show that the portfolio approach gives the highest accuracy. PMID- 27006869 TI - Histological and micro-computed tomographic observations after maxillary sinus augmentation with porous hydroxyapatite alloplasts: a clinical case series. AB - BACKGROUND: It is important to visualize the phenomenon which occurs in actual clinical cases to decide the timing of implant placement subsequently after sinus graft. Although several clinical cases of bone augmentation using xenograft have been evaluated, the number of those reports which have described bone remodeling by alloplasty are not sufficient. FINDINGS: In the present report, to investigate bone remodeling histologically after maxillary sinus augmentation with porous hydroxyapatite alloplast, bone cores from the sinus floor of three female nonsmoking patients (aged 64-73 years) were collected 6 months after sinus lift surgery, embedded in methyl methacrylate resin, and prepared by conventional methods. Bone architecture and graft residues were evaluated by micro-computed tomography of the same specimens. Hematoxylin-eosin and Villanueva-Goldner staining revealed mature osteoblasts and multinucleated osteoclasts on the grafted sinus floor and surface of residual hydroxyapatite particles. The particulate interspace was partially filled with osteoid and calcified tissue and showed active vascularization. CONCLUSION: The results suggested that bone regeneration and angiogenesis within and between porous hydroxyapatite particles were sufficiently found after 6 month histologically in the grafted sinus floor. PMID- 27006872 TI - Application of an integrated multi-criteria decision making AHP-TOPSIS methodology for ETL software selection. AB - Actually, a set of ETL software (Extract, Transform and Load) is available to constitute a major investment market. Each ETL uses its own techniques for extracting, transforming and loading data into data warehouse, which makes the task of evaluating ETL software very difficult. However, choosing the right software of ETL is critical to the success or failure of any Business Intelligence project. As there are many impacting factors in the selection of ETL software, the same process is considered as a complex multi-criteria decision making (MCDM) problem. In this study, an application of decision-making methodology that employs the two well-known MCDM techniques, namely Analytic Hierarchy Process (AHP) and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) methods is designed. In this respect, the aim of using AHP is to analyze the structure of the ETL software selection problem and obtain weights of the selected criteria. Then, TOPSIS technique is used to calculate the alternatives' ratings. An example is given to illustrate the proposed methodology. Finally, a software prototype for demonstrating both methods is implemented. PMID- 27006871 TI - Embolization for type 2 endoleak with sac expansion after endovascular repair of abdominal aortic aneurysm: safety and effectiveness. AB - To evaluate the safety and outcome of embolization as treatment for persistent type 2 endoleak (T2EL) occurring after abdominal aortic stent graft implantation. This retrospective study included seven consecutive patients (one female, six males, mean age 72 years, range 66-88 years) with T2EL between January 2011 and September 2012. In all, T2EL was associated with an increase more than 5 mm in the aneurysm. The endoleak cavity or feeding artery was embolized with coils and/or n-butyl cyanoacrylate. Clinical success was defined as regression or stabilization of the aneurysm sac irrespective of residual endoleaks on follow-up CT studies. At the time of T2EL intervention, mean aneurysm sac diameter was 63 mm (range 52-72 mm), and mean increase size of aneurysm sac diameter was 7 mm (range 5-13). Mean follow-up period was 6.0 +/- 6.2 months (range 3-18 months). Our technical success rate was 100 %. Clinical success was obtained in 5 (71.4 %) of the seven patients. One patient was embolized three times due to sac expansion. T2EL was treated by transarterial embolization in eight procedures, and one procedure was performed by direct puncture embolization. There were no major complications; two procedures elicited minor complications: transient back pain and muscle weakness of the left lower leg. We suggest embolization was safe and effective treatment, a less invasive treatment option comparison to open repair, as one choice to address T2EL. PMID- 27006873 TI - Phytochemical analysis, antimicrobial and antioxidant activities of Euphorbia golondrina L.C. Wheeler (Euphorbiaceae Juss.): an unexplored medicinal herb reported from Cameroon. AB - This study aimed at determining the phytochemical constituents of Euphorbia golondrina L.C. Wheeler, an alien invasive medicinal herb that is used for the treatment of gastroenteritis related ailments, diabetes, conjunctivitis, gastritis, enterocolitis, tonsillitis, vaginitis, hemorrhoids, prostatism, warts and painful swellings by the Mundani people of the mount Bambouto Caldera in SouthWestern Cameroon, and to evaluate its in vitro antimicrobial and antioxidant activities. Susceptibility testing by agar well diffusion assay revealed good antibacterial activity with inhibition zone diameter of 20 +/- 1.1 mm against Bacillus cereus followed by Staphylococcus aureus with inhibition zone diameter of 17 +/- 1.6 mm which was significantly lower (P < 0.05) than the positive control (amoxicillin). None of the fungi was inhibited by the acetone extract of E. golondrina except Candida albicans wherein the zone of inhibition was not significantly different from that of the positive control (Amphotericin B). The ABTS scavenging activity of E. golondrina was higher than that of gallic acid and BHT at concentrations greater than 0.1 and 0.2 mg/mL respectively while at all concentrations, nitric oxide scavenging activity was higher than those of both rutin and vitamin C. GC-MS profile of E. golondrina steam distilled volatiles revealed that the plant has potent phytoconstituent classes such as sesquiterpenes, monoterpenes, alkaloids, phenolics and aromatic hydrocarbons. Among the 30 compounds identified, caryophyllene oxide (14.16 %), camphor (9.41 %) and phytol (5.75 %) were the major compounds. Further structural characterisation based on (1)H and (13)C NMR is required to demonstrate structural integrity including correct stereochemistry. The current study partially justifies the ethnomedicinal uses of E. golondrina in Cameroon. PMID- 27006874 TI - Recurrent ectopic pregnancy as a unique clinical sub group: a case control study. AB - BACKGROUND: Women with recurrent ectopic pregnancy (EP) represent a unique cohort of patients in whom diagnostic expertise is paramount. We determined whether recurrent EP is associated with significant differences in patient demographics, clinical presentation, risk factors and surgical findings when compared with primary EP. METHODS: A retrospective case-control study of all EPs diagnosed from 2003 to 2014, at Whipps Cross University Hospital, London. RESULTS: In the above period 849 EPs were surgically managed (758 primary EPs and 91 recurrent EPs). Recurrent EPs were significantly older than primary EPs (32.2 +/- 5.08 vs. 30.5 +/- 5.83 years, p < 0.05). They presented at a significantly earlier gestation (5.99 +/- 1.08 vs. 6.52 +/- 1.81 weeks, p < 0.05) and with a significantly lower primary betaHCG (3176 +/- 7350 vs. 6243 +/- 12,282, p < 0.05). Recurrent EPs were significantly more likely to have a positive history of tubal or pelvic surgery (61.5 % vs. 3.5 %, p < 0.05 and 53.8 vs. 14 %, p < 0.05). At surgery, primary EPs had a significantly greater volume of hemoperitoneum (592 +/- 850 vs. 249 +/- 391 ml, p < 0.05), whereas recurrent EPs were significantly more likely to have contralateral pathology (31.1 vs. 9.8 %, p < 0.05). Regression analysis showed that the parameters of age, gestational age at presentation, first betaHCG level, positive history of previous tubal surgery and previous ectopic pregnancy differ in women at risk of a recurrent EP when compared to women not at risk of a recurrent ectopic (AUC, 0.844). CONCLUSIONS: We conclude that recurrent EPs may represent a unique sub-group of patients with EP. PMID- 27006875 TI - Tissue damage by laser radiation: an in vitro comparison between Tm:YAG and Ho:YAG laser on a porcine kidney model. AB - The understanding of tissue damage by laser radiation is very important for the safety in the application of surgical lasers. The objective of this study is to evaluate cutting, vaporization and coagulation properties of the 2 um Tm:YAG laser (LISA Laser Products OHG, GER) in comparison to the 2.1 um Ho:YAG laser (Coherent Medical Group, USA) at different laser power settings in an in vitro model of freshly harvested porcine kidneys. Laser radiation of both laser generators was delivered by using a laser fiber with an optical core diameter of 550 um (RigiFib, LISA Laser GER). Freshly harvested porcine kidneys were used as tissue model. Experiments were either performed in ambient air or in aqueous saline. The Tm:YAG laser was adjusted to 5 W for low and 120 W for the high power setting. The Ho:YAG laser was adjusted to 0.5 J and 10 Hz (5 W average power) for low power setting and to 2.0 J and 40 Hz (80 W average power) for high power setting, accordingly. The specimens of the cutting experiments were fixed in 4 % formalin, embedded in paraffin and stained with Toluidin blue. The laser damage zone was measured under microscope as the main evaluation criteria. Laser damage zone consists of an outer coagulation zone plus a further necrotic zone. In the ambient air experiments the laser damage zone for the low power setting was 745 +/- 119 um for the Tm:YAG and 614 +/- 187 um for the Ho:YAG laser. On the high power setting, the damage zone was 760 +/- 167 um for Tm:YAG and 715 +/- 142 um for Ho:YAG. The incision depth in ambient air on the low power setting was 346 +/ 199 um for Tm:YAG, 118 +/- 119 um for Ho:YAG. On the high power setting incision depth was 5083 +/- 144 um (Tm:YAG) and 1126 +/- 383 um (Ho:YAG) respectively. In the saline solution experiments, the laser damage zone was 550 +/- 137 um (Tm:YAG) versus 447 +/- 65 um (Ho:YAG), on the low power setting and 653 +/- 137 um (Tm:YAG) versus 677 +/- 134 um (Ho:YAG) on the high power setting. Incision depth was 1214 +/- 888 um for Ho:YAG whereas Tm:YAG did not cut tissue at 5 W in saline solution. On the high power setting, the incision depth was 4050 +/- 1058 um for Tm:YAG and 4083 +/- 520 um for Ho:YAG. Both lasers create similar laser damage zones of <1 mm in ambient air and in saline solution. These in vitro experiments correspond well with in vivo experiments. Thereby, Tm:YAG offers a cutting performance, coagulation and safety profile similar to the standard Ho:YAG lasers in urological surgery. PMID- 27006876 TI - The stock-flow model of spatial data infrastructure development refined by fuzzy logic. AB - The system dynamics technique has been demonstrated to be a proper method by which to model and simulate the development of spatial data infrastructures (SDI). An SDI is a collaborative effort to manage and share spatial data at different political and administrative levels. It is comprised of various dynamically interacting quantitative and qualitative (linguistic) variables. To incorporate linguistic variables and their joint effects in an SDI-development model more effectively, we suggest employing fuzzy logic. Not all fuzzy models are able to model the dynamic behavior of SDIs properly. Therefore, this paper aims to investigate different fuzzy models and their suitability for modeling SDIs. To that end, two inference and two defuzzification methods were used for the fuzzification of the joint effect of two variables in an existing SDI model. The results show that the Average-Average inference and Center of Area defuzzification can better model the dynamics of SDI development. PMID- 27006877 TI - Some fixed point theorems in generating space of b-quasi-metric family. AB - The purpose of this work is to study some properties of "Generating space of b quasi-metric family"(simply [Formula: see text]-family) and derive some fixed point theorems using some standard contractions. Presented theorems extend and generalize many well-known results in the literature of fixed point theory . PMID- 27006878 TI - Association of high-sensitivity C-reactive protein and uric acid with the metabolic syndrome components. AB - Metabolic syndrome (MetS) has been found to be associated with inflammatory molecules. This study was conducted among 125 MetS patients at B P Koirala Institute of Health Sciences, Dharan, Nepal to find an association of high sensitivity C-reactive protein (hs-CRP) and serum uric acid with MetS components. Anthropometric measurements, blood pressure, medical history and blood samples were taken. Estimation of hs-CRP, serum uric acid, blood glucose, triglyceride and high density lipoprotein (HDL) cholesterol was done. hs-CRP had positive correlation with blood glucose (r = 0.2, p = 0.026) and negative with HDL cholesterol (r = -0.361, p < 0.001). Serum uric acid had positive correlation with waist circumference (r = 0.178, p = 0.047). Patients with elevated hs-CRP and uric acid had higher waist circumference (p = 0.03), diastolic BP (p = 0.002) and lower HDL cholesterol (p = 0.004) than others. Elevated hs-CRP and high uric acid were individually associated with higher odds for low HDL cholesterol (7.992; 1.785-35.774, p = 0.002) and hyperglycemia (2.471; 1.111-5.495, p = 0.029) respectively. Combined rise of hs-CRP and uric acid was associated with severity of MetS (p < 0.001) and higher odds for hyperglycemia (8.036; 2.178 29.647, p = 0.001) as compared to individual rise of hs-CRP or uric acid. The present study demonstrates that hs-CRP and serum uric acid are associated with MetS components, and the combined rise of hs-CRP and uric acid is associated with the increase in severity of MetS. PMID- 27006879 TI - Adherence assessment of patients with metastatic solid tumors who are treated in an oncology group practice. AB - Due to the increase of oral agents nonadherence is an emerging challenge in cancer care. We evaluated how well different assessments match and how adherence could be measured in routine care. For this purpose patients suffering from metastatic solid tumors who were treated with oral anticancer drugs in an oncology group practice were surveyed. Attending oncologists answered a questionnaire, too, and a retrospective analysis of prescription data was conducted. Caregivers who were eligible for an interview were surveyed additionally. 128 patients (70 % female) with a median age of 69 years (36-88) took part, 95 % of all approached patients. 56 % suffered from metastatic breast cancer, 44 % from other metastatic solid tumors. 65 caregivers (60 % female) with a median age of 62 years (21-82) were interviewed as well. Patients were assessed in 84 % as very reliable in medication-taking by their oncologists. This high adherence rate was supported by patients, caregivers and prescription data. However, concordance between assessments of patients, caregivers and oncologists was not substantial. Our method of considering different perspectives to assess adherence has to be improved and validated but could help to evaluate adherence with oral cancer therapy in routine care. PMID- 27006880 TI - Synthesis of hexahydrofuro[3,2-c]quinoline, a martinelline type analogue and investigation of its biological activity. AB - BACKGROUND: Candida susceptibility commonly occurs in breast cancer patients. Of which, Candida albicans is considered as a common pathogen causing candidiasis. Martinella iquitosensis (Bignoniaceae) is one of the species belonged to Martinella, distributed widely in Amazon basin. Its root extract yielded two complex substituted tetrahydroquinolines, Martinelline and Martinellic acid which were the first natural non-peptide bradykinin receptor antagonists identified. FINDINGS: In this study, a novel martinelline type analogue, named 2,3,3a,4,5,9b hexahydro-8-phenoxy-4-(pyridin-2-yl)furo[3,2-c]quinoline, was synthesized and its preliminary anticancer activity and antifungal potential were investigated. This compound showed potential anticancer activity against MDAMB-231 breast cancer cells. Meanwhile it could enhance the fungistatic activity of miconazole against Candida albicans. CONCLUSIONS: These findings provide an implication for the continue investigation and development of martinelline type analogues as therapeutic agents in the future. PMID- 27006881 TI - Effects of properties of metal-contaminated soils on bacterial bioluminescence activity, seed germination, and root and shoot growth. AB - This study examined the effects of several factors (metal contents and soil properties) on bacterial bioluminescence activity, seed germination and root/shoot growth of Lactuca in metal-contaminated soils. Each bioassay showed different sensitivities to extractants of soil samples. Average sensitivities of the bioassay were in the following order: root growth > bioluminescence >= shoot growth >= seed germination. Both total and weak acid-extracted metal contents showed no observable correlations with the activity of any bioassays (r(2) < 0.279). However, reasonable correlations were observed between the bioluminescence activity and organics (r(2) = 0.7198) as well as between root growth and CEC (r(2) = 0.6676). Effects of soils were difficult to generalize since they were dependent on many factors, such as soil properties, metal contents, and the organism used in each test. Nonetheless, these results indicated that a battery of bioassays is an effective strategy for assessment of contaminated soils. Furthermore, specific soil factors were shown to more influence on soil toxicity, depending on the type of bioassay. PMID- 27006882 TI - Detecting and classifying method based on similarity matching of Android malware behavior with profile. AB - Mass-market mobile security threats have increased recently due to the growth of mobile technologies and the popularity of mobile devices. Accordingly, techniques have been introduced for identifying, classifying, and defending against mobile threats utilizing static, dynamic, on-device, and off-device techniques. Static techniques are easy to evade, while dynamic techniques are expensive. On-device techniques are evasion, while off-device techniques need being always online. To address some of those shortcomings, we introduce Andro-profiler, a hybrid behavior based analysis and classification system for mobile malware. Andro profiler main goals are efficiency, scalability, and accuracy. For that, Andro profiler classifies malware by exploiting the behavior profiling extracted from the integrated system logs including system calls. Andro-profiler executes a malicious application on an emulator in order to generate the integrated system logs, and creates human-readable behavior profiles by analyzing the integrated system logs. By comparing the behavior profile of malicious application with representative behavior profile for each malware family using a weighted similarity matching technique, Andro-profiler detects and classifies it into malware families. The experiment results demonstrate that Andro-profiler is scalable, performs well in detecting and classifying malware with accuracy greater than 98 %, outperforms the existing state-of-the-art work, and is capable of identifying 0-day mobile malware samples. PMID- 27006883 TI - Double chamber right ventricle in Williams syndrome: a rare cardiac anomaly reported. AB - Cardiovascular abnormality is the most consistent finding and occur in almost 80 % of all Williams syndrome (WS). Although a number of cardiovascular defects are common to WS, the majority presents in some form of arterial stenosis whereas supravalvular aortic stenosis is the most common one. Here we describe a 12 year old boy with elfin facies, presenting with urinary incontinence and a systolic murmur in right upper parasternal region. Echocardiography showed presence of double chambered right ventricle (DCRV) along with supravalvular aortic stenosis (SVAS) and coronary artery aneurysms, left pulmonary artery stenosis and multiple bladder diverticula in CT abdomen. With the clinical suspicion the diagnosis of WS was made and confirmed by fluorescent in situ hybridisation (FISH) study showing deletion in 7q11.23. Though different forms of arterial stenosis at multiple sites have been demonstrated in WS, DCRV in Williams syndrome is not reported till date in medical literature. PMID- 27006885 TI - Multiplicative noise removal using primal-dual and reweighted alternating minimization. AB - Multiplicative noise removal is an important research topic in image processing field. An algorithm using reweighted alternating minimization to remove this kind of noise is proposed in our preliminary work. While achieving good results, a small parameter is needed to avoid the denominator vanishing. We find that the parameter has important influence on numerical results and has to be chosen carefully. In this paper a primal-dual algorithm is designed without the artificial parameter. Numerical experiments show that the new algorithm can get a good visual quality, overcome staircase effects and preserve the edges, while maintaining high signal-to-noise ratio. PMID- 27006884 TI - Laplace transform homotopy perturbation method for the approximation of variational problems. AB - This article proposes the application of Laplace Transform-Homotopy Perturbation Method and some of its modifications in order to find analytical approximate solutions for the linear and nonlinear differential equations which arise from some variational problems. As case study we will solve four ordinary differential equations, and we will show that the proposed solutions have good accuracy, even we will obtain an exact solution. In the sequel, we will see that the square residual error for the approximate solutions, belongs to the interval [0.001918936920, 0.06334882582], which confirms the accuracy of the proposed methods, taking into account the complexity and difficulty of variational problems. PMID- 27006886 TI - Prevalence of genotypes and subtypes of hepatitis B viruses in Bangladeshi population. AB - The genetic variability of hepatitis B virus (HBV) represents a challenge for the sensitivity of immunologic and molecular based assays. Based on sequence divergences in the entire genome of >8 %, HBV genomes have been classified into ten genotypes designated as A to J. The aim of this study was to determine HBV genotypes and subtype in samples of HBV infected patients in Bangladesh. The sera samples were collected from chronically infected HBV patients. At first the DNA positive HBV samples were screened by EIA in our laboratory and the 1063 bp region of surface gene was amplified, sequenced and genotyped by sequence analysis. The same sequences were also used for subtypes and mutational analyses. After that, genotyping was also carried out by nested PCR using genotype specific primers in the same region of HBV surface gene. A total of 39 samples were sequencing to find out the genotypes and subtypes. It was found that the prevalent genotype was genotype C (subgenotype C1) which accounted for 48.7 %. The other genotypes found were genotype A (23.1 %) and genotype D (28.2 %). Predominant subtypes in Bangladesh were adr (41 %) followed by subtype adw2 (28.2 %), ayw3 (25.6 %), and others. Additionally, genotyping was also done by nested PCR using type-specific primers. In this method, out of 17 samples 6 were found to be genotype C, followed by genotype D (4 of 17) and genotype A (3 of 17). In PCR-based genotyping system we also observed the mix genotypes; 3 samples contained both genotype A and D, and 2 samples contained both C and D. The genetic diversity of HBV and distribution of its genotypes and subtypes amongst Bangladeshi population were done in this study, which will help us to provide information regarding circulating genotypes in this region and also help physicians to prescribe proper antiviral/interferon therapy. PMID- 27006887 TI - Assessment of the effects of phenanthrene and its nitrogen heterocyclic analogues on microbial activity in soil. AB - Microbes are susceptible to contaminant effects, and high concentrations of chemical in soil can impact on microbial growth, density, viability and development. As a result of relative sensitivity of microbes to contaminants, toxicity data are important in determining critical loads or safe levels for contaminants in soil. Therefore the aim of this study was to assess the impact of phenanthrene and the 3-ring nitrogen-containing polycyclic aromatic hydrocarbons (N-PAHs) on soil microbial respiration. Soil samples were amended with phenanthrene and its 3-ring nitrogen-containing analogues and respiration rates (using substrate induced respiration), CO2 production inhibition and/or stress and total culturable microbial numbers were measured over a 90 days soil-contact time. The study showed that inhibition of phenanthrene amended soils occurred in the first 60 days, while the nitrogen-containing analogues impacted on respiration with increased concentration and contact time. Time dependent inhibitions were more than 25 % portraying N-PAHs toxic and inhibitory effects on microbial synthesis of the added carbon substrate. Further, statistical analysis of data revealed statistically significant differences in the respiration rates over time (p < 0.05). This suggests that soil microorganisms may be more sensitive to N-PAHs in soil than the homocyclic PAH analogues. This current study provides baseline toxicity data to the understanding of the environmental impact of N-PAHs, and assists science-based decision makers for improved management of N PAH contaminated sites. PMID- 27006888 TI - A uniformly valid approximation algorithm for nonlinear ordinary singular perturbation problems with boundary layer solutions. AB - This paper is concerned with two-point boundary value problems for singularly perturbed nonlinear ordinary differential equations. The case when the solution only has one boundary layer is examined. An efficient method so called Successive Complementary Expansion Method (SCEM) is used to obtain uniformly valid approximations to this kind of solutions. Four test problems are considered to check the efficiency and accuracy of the proposed method. The numerical results are found in good agreement with exact and existing solutions in literature. The results confirm that SCEM has a superiority over other existing methods in terms of easy-applicability and effectiveness. PMID- 27006889 TI - Developing checklists to prevent diagnostic error in Emergency Room settings. AB - BACKGROUND: Checklists have been shown to improve performance of complex, error prone processes. To develop a checklist with potential to reduce the likelihood of diagnostic error for patients presenting to the Emergency Room (ER) with undiagnosed conditions. METHODS: Participants included 15 staff ER physicians working in two large academic centers. A rapid cycle design and evaluation process was used to develop a general checklist for high-risk situations vulnerable to diagnostic error. Physicians used the general checklists and a set of symptom-specific checklists for a period of 2 months. We conducted a mixed methods evaluation that included interviews regarding user perceptions and quantitative assessment of resource utilization before and after checklist use. RESULTS: A general checklist was developed iteratively by obtaining feedback from users and subject matter experts, and was trialed along with a set of specific checklists in the ER. Both the general and the symptom-specific checklists were judged to be helpful, with a slight preference for using symptom-specific lists. Checklist use commonly prompted consideration of additional diagnostic possibilities, changed the working diagnosis in approximately 10% of cases, and anecdotally was thought to be helpful in avoiding diagnostic errors. Checklist use was prompted by a variety of different factors, not just diagnostic uncertainty. None of the physicians used the checklists in collaboration with the patient, despite being encouraged to do so. Checklist use did not prompt large changes in test ordering or consultation. CONCLUSIONS: In the ER setting, checklists for diagnosis are helpful in considering additional diagnostic possibilities, thus having potential to prevent diagnostic errors. Inconsistent usage and using the checklists privately, instead of with the patient, are factors that may detract from obtaining maximum benefit. Further research is needed to optimize checklists for use in the ER, determine how to increase usage, to evaluate the impact of checklist utilization on error rates and patient outcomes, to determine how checklist usage affects test ordering and consultation, and to compare checklists generally with other approaches to reduce diagnostic error. PMID- 27006890 TI - Communication breakdowns and diagnostic errors: a radiology perspective. AB - Timely and accurate communication is essential to safe and effective health care. Despite increased awareness over the past decade of the frequency of medical errors and greater efforts directed towards improving patient safety, patient harm due to communication breakdowns remains a significant problem. Communication problems related to diagnostic testing may account for nearly half of all errors made by typical primary care physicians in their medical practices. This article provides an overview of communication breakdowns in the context of radiology related diagnostic errors. In radiology, communication breakdowns between radiologists, referring clinicians, and patients can lead to failure of critical information to be relayed, resulting in delayed or missed diagnosis. New technologies, such electronic health records (EHRs), contribute to the increasing complexity of communication in health care, but if used correctly, they can provide several benefits to safe and effective communication. To address the complexity of communication breakdowns, a multifaceted sociotechnical approach is needed to address both technical and non-technical aspects of health care delivery. The article also provides some future directions in reducing communication breakdowns related to diagnostic testing, including proactive risk assessment of communication practices using recently released SAFER self assessment guides. PMID- 27006891 TI - Breakdowns in communication of radiological findings: an ethical and medico-legal conundrum. AB - Communication problems in diagnostic testing have increased in both number and importance in recent years. The medical and legal impact of failure of communication is dramatic. Over the past decades, the courts have expanded and strengthened the duty imposed on radiologists to timely communicate radiologic abnormalities to referring physicians and perhaps the patients themselves in certain situations. The need to communicate these findings goes beyond strict legal requirements: there is a moral imperative as well. The Code of Medical Ethics of the American Medical Association points out that "Ethical values and legal principles are usually closely related, but ethical obligations typically exceed legal duties." Thus, from the perspective of the law, radiologists are required to communicate important unexpected findings to referring physicians in a timely fashion, or alternatively to the patients themselves. From a moral perspective, radiologists should want to effect such communications. Practice standards, moral values, and ethical statements from professional medical societies call for full disclosure of medical errors to patients affected by them. Surveys of radiologists and non-radiologic physicians reveal that only few would divulge all aspects of the error to the patient. In order to encourage physicians to disclose errors to patients and assist in protecting them in some manner if malpractice litigation follows, more than 35 states have passed laws that do not allow a physician's admission of an error and apologetic statements to be revealed in the courtroom. Whether such disclosure increases or decreases the likelihood of a medical malpractice lawsuit is unclear, but ethical and moral considerations enjoin physicians to disclose errors and offer apologies. PMID- 27006892 TI - Targeting hyaluronan for the treatment of pancreatic ductal adenocarcinoma. AB - Progression of cancer is often associated with interactions between cancer cells and extracellular matrix (ECM) surrounding them. Increasing evidence has suggested that accumulation of hyaluronan (HA), a major component of ECM, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma (PDAC) is characterized typically by a dense desmoplastic stroma with a large amount of HA, making this molecule as an attractive target for therapy. Several studies have shown efficacy of inhibitors of HA synthesis or signaling for the treatment of PDAC. Recent studies have also demonstrated substantial improvements in the effects of chemotherapy by a targeted depletion of stromal HA in PDAC using an enzymatic agent. Thus, targeting HA has been recognized as a promising therapeutic strategy to treat this highly aggressive neoplasm. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA. PMID- 27006894 TI - Editorial to the Feature article "Artemisinin anti-malarial drugs in China". PMID- 27006895 TI - Artemisinin anti-malarial drugs in China. AB - Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the "whole nation" system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements. PMID- 27006893 TI - Injected nanocrystals for targeted drug delivery. AB - Nanocrystals are pure drug crystals with sizes in the nanometer range. Due to the advantages of high drug loading, platform stability, and ease of scaling-up, nanocrystals have been widely used to deliver poorly water-soluble drugs. Nanocrystals in the blood stream can be recognized and sequestered as exogenous materials by mononuclear phagocytic system (MPS) cells, leading to passive accumulation in MPS-rich organs, such as liver, spleen and lung. Particle size, morphology and surface modification affect the biodistribution of nanocrystals. Ligand conjugation and stimuli-responsive polymers can also be used to target nanocrystals to specific pathogenic sites. In this review, the progress on injected nanocrystals for targeted drug delivery is discussed following a brief introduction to nanocrystal preparation methods, i.e., top-down and bottom-up technologies. PMID- 27006896 TI - Mechanistic studies of the transport of peimine in the Caco-2 cell model. AB - Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations <200 MUmol/L, the effect of peimine concentration, pH, temperature, efflux transport protein inhibitors and EDTA-Na2 on peimine transport were studied. The results show that peimine transport is concentration dependent; that at pH 6.0 and 7.4, the P app(AP-BL) of peimine is not significantly different but the P app(BL-AP)) is; that both P app(AP-BL) and P app(BL-AP) at 4 degrees C are significantly higher than their corresponding values at 37 degrees C; that the P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary, the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp. PMID- 27006897 TI - Sodium humate accelerates cutaneous wound healing by activating TGF-beta/Smads signaling pathway in rats. AB - Sodium humate (HA-Na) has been topically used as a wound healing and anti inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague-Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor beta1, 2, 3 (TGF-beta1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-beta/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing. PMID- 27006898 TI - Three pairs of alkaloid enantiomers from the root of Isatis indigotica. AB - Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(-)-1 and (+)-1], phaitanthrin A and epiphaitanthrin A [(-)-2 and (+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(-)-3 and (+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column. Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism (ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1 b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A [(-)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products. PMID- 27006899 TI - Flavonoid profiling of a traditional Chinese medicine formula of Huangqin Tang using high performance liquid chromatography. AB - The quality control processes for herbal medicines have been problematic. Flavonoids are the major active components of Huangqin Tang (HQT, a traditional Chinese medicine formula). In this study, we used a combinative method approach consisting of chromatographic fingerprinting (high performance liquid chromatography; HPLC), quantitative methods and a pharmacodynamic evaluation model to analyze the flavonoids of HQT obtained from different sources. Ten batches of HQT were analyzed by the HPLC fingerprinting method and 26 common peaks were detected, of which 23 peaks corresponded with the chemical profile of HQT. In addition, 11 major compounds were identified by LC-MS analysis (liquid chromatography-tandem mass spectrometer; LC-MS (n) ) and quantified by the HPLC quantitative method approach. The studied 10 batches of HQT were found to be homogeneous in their composition with a similarity between 0.990 and 1.000. The distribution of the 11 identified compounds was found to be very similar among the batches. Only slight pharmacodynamic differences were detected between the different batches, confirming the homogeneity of HQT. The results of this study prove that the combination of chromatographic fingerprinting and quantitative analysis can be readily used for comprehensive quality control of herbal medicines. PMID- 27006900 TI - Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites. AB - Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t 1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t 1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable. PMID- 27006901 TI - Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique. AB - Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decreases the rate and amount of drug transferred. In conclusion, the flow cytometric technique is a suitable technique to study drug transfer from these carriers to large lipophilic acceptors. Monoolein cubic particles with their unique structure can be used successfully as a drug carrier with slow drug release compared with trimyristin nanoparticles. PMID- 27006902 TI - Investigation of free amino acid, total phenolics, antioxidant activity and purine alkaloids to assess the health properties of non-Camellia tea. AB - To find novel functional beverages from folk teas, 33 species of frequently used non-Camellia tea (plants other than Camellia) were collected and compared with Camellia tea (green tea, pu-erh tea and black tea) for the first time. Data are reported here on the quantities of 20 free amino acids (FAAs) and three purine alkaloids (measured by UHPLC), total polyphenols (measured by Folin-Ciocalteu assay), and antioxidant activity (DPPH). The total amounts of FAAs in non Camellia tea (0.62-18.99 mg/g) are generally less than that of Camellia tea (16.55-24.99 mg/g). However, for certain FAAs, the quantities were much higher in some non-Camellia teas, such as gamma-aminobutyric acid in teas from Ampelopsis grossedentata, Isodon serra and Hibiscus sabdariffa. Interestingly, theanine was detected in tea from Potentilla fruticosa (1.16+/-0.81 mg/g). Furthermore, the content of polyphenols in teas from A. grossedentata, Acer tataricum subsp. ginnala are significantly higher than those from Camellia tea; teas from I. serra, Pistacia chinensis and A. tataricum subsp. ginnala have remarkable antioxidant activities similar to the activities from green tea (44.23 MUg/mL). Purine alkaloids (caffeine, theobromine and theophylline) were not detected in non-Camellia teas. The investigation suggest some non-Camellia teas may be great functional natural products with potential for prevention of chronic diseases and aging, by providing with abundant polyphenols, antioxidants and specific FAAs. PMID- 27006903 TI - Applying a free-water correction to diffusion imaging data uncovers stress related neural pathology in depression. AB - Diffusion tensor imaging (DTI) holds promise for developing our understanding of white-matter pathology in major depressive disorder (MDD). Variable findings in DTI-based investigations of MDD, however, have thwarted development of this literature. Effects of extra-cellular free-water on the sensitivity of DTI metrics could account for some of this inconsistency. Here we investigated whether applying a free-water correction algorithm to DTI data could improve the sensitivity to detect clinical effects using DTI metrics. Only after applying this correction, we found: a) significantly decreased fractional anisotropy and axial diffusivity (AD) in the left inferior fronto-occipital fasciculus (IFOF) in MDD; and b) increased self-reported stress that significantly correlated with decreased IFOF AD in depression. We estimated and confirmed the robustness of differences observed between free-water corrected and uncorrected approaches using bootstrapping. We conclude that applying a free-water correction to DTI data increases the sensitivity of DTI-based metrics to detect clinical effects in MDD. PMID- 27006905 TI - How Extended Is Wernicke's Area? Meta-Analytic Connectivity Study of BA20 and Integrative Proposal. AB - Understanding the functions of different brain areas has represented a major endeavor of contemporary neurosciences. The purpose of this paper was to pinpoint the connectivity of Brodmann area 20 (BA20) (inferior temporal gyrus, fusiform gyrus) in language tasks. A meta-analysis was conducted to assess the language network in which BA20 is involved. The DataBase of Brainmap was used; 11 papers corresponding to 12 experimental conditions with a total of 207 subjects were included in this analysis. Our results demonstrated seven clusters of activation including other temporal lobe areas (BA3, BA21), the insula, and the prefrontal cortex; minor clusters in the cingulate gyrus and the occipital lobe were observed; however, the volumes of all the activation clusters were small. Our results suggest that regardless of BA20 having certain participation in language processes it cannot be considered as a core language processing area (Wernicke's area); nonetheless, it could be regarded as kind of language processing marginal area, participating in "extended Wernicke's area" or simply "Wernicke's system." It is suggested that "core Wernicke's area" roughly corresponds to BA21, BA22, BA41, and BA42, while a "language associations area" roughly corresponds to BA20, BA37, BA38, BA39, and BA40 ("extended Wernicke's area" or "Wernicke's system"). PMID- 27006904 TI - Cocaine-conditioned odor cues without chronic exposure: Implications for the development of addiction vulnerability. AB - Adolescents are highly vulnerable to addiction and are four times more likely to become addicted at first exposure than at any other age. The dopamine D1 receptor, which is typically overexpressed in the normal adolescent prefrontal cortex, is involved in drug cue responses and is associated with relapse in animal models. In human drug addicts, imaging methods have detected increased activation in response to drug cues in reward- and habit-associated brain regions. These same methods can be applied more quantitatively to rodent models. Here, changes in neuronal activation in response to cocaine-conditioned cues were observed using functional magnetic resonance imaging in juvenile rats that were made to over-express either D1 receptors or green fluorescent protein by viral mediated transduction. Reduced activation was observed in the amygdala and dopamine cell body regions in the low cue-preferring/control juvenile rats in response to cocaine cues. In contrast, increased activation was observed in the dorsal striatum, nucleus accumbens, prefrontal cortex, and dopamine cell bodies in high cue-preferring/D1 juveniles. The increase in cue salience that is mediated by increased D1 receptor density, rather than excessive cocaine experience, appears to underlie the transition from aversion to reward in cue induced neural response and may form the basis for habit-forming vulnerability. PMID- 27006906 TI - Hybrid Discrete Wavelet Transform and Gabor Filter Banks Processing for Features Extraction from Biomedical Images. AB - A new methodology for automatic feature extraction from biomedical images and subsequent classification is presented. The approach exploits the spatial orientation of high-frequency textural features of the processed image as determined by a two-step process. First, the two-dimensional discrete wavelet transform (DWT) is applied to obtain the HH high-frequency subband image. Then, a Gabor filter bank is applied to the latter at different frequencies and spatial orientations to obtain new Gabor-filtered image whose entropy and uniformity are computed. Finally, the obtained statistics are fed to a support vector machine (SVM) binary classifier. The approach was validated on mammograms, retina, and brain magnetic resonance (MR) images. The obtained classification accuracies show better performance in comparison to common approaches that use only the DWT or Gabor filter banks for feature extraction. PMID- 27006907 TI - Spectroscopic Detection of Caries Lesions. AB - Background. A caries lesion causes changes in the optical properties of the affected tissue. Currently a caries lesion can be detected only at a relatively late stage of development. Caries diagnosis also suffers from high interobserver variance. Methods. This is a pilot study to test the suitability of an optical diffuse reflectance spectroscopy for caries diagnosis. Reflectance visible/near infrared spectroscopy (VIS/NIRS) was used to measure caries lesions and healthy enamel on extracted human teeth. The results were analysed with a computational algorithm in order to find a rule-based classification method to detect caries lesions. Results. The classification indicated that the measured points of enamel could be assigned to one of three classes: healthy enamel, a caries lesion, and stained healthy enamel. The features that enabled this were consistent with theory. Conclusions. It seems that spectroscopic measurements can help to reduce false positives at in vitro setting. However, further research is required to evaluate the strength of the evidence for the method's performance. PMID- 27006908 TI - Comparison of Respiratory Resistance Measurements Made with an Airflow Perturbation Device with Those from Impulse Oscillometry. AB - The airflow perturbation device (APD) has been developed as a portable, easy to use, and a rapid response instrument for measuring respiratory resistance in humans. However, the APD has limited data validating it against the established techniques. This study used a mechanical system to simulate the normal range of human breathing to validate the APD with the clinically accepted impulse oscillometry (IOS) technique. The validation system consisted of a sinusoidal flow generator with ten standardized resistance configurations that were shown to represent a total range of resistances from 0.12 to 0.95 kPa.L(-1) .s (1.2-9.7 cm H2O.L(-1) .s). Impulse oscillometry measurements and APD measurements of the mechanical system were recorded and compared at a constant airflow of 0.15 L.s( 1). Both the IOS and APD measurments were accurate in assessing nominal resistance. In addition, a strong linear relationship was observed between APD measurements and IOS measurements (R (2) = 0.999). A second series of measurements was made on ten human volunteers with external resistors added in their respiratory flow paths. Once calibrated with the mechanical system, the APD gave respiratory resistance measurements within 5% of IOS measurements. Because of their comparability to IOS measurements, APD measurements are shown to be valid representations of respiratory resistance. PMID- 27006909 TI - A MATLAB-Based Boundary Data Simulator for Studying the Resistivity Reconstruction Using Neighbouring Current Pattern. AB - Phantoms are essentially required to generate boundary data for studying the inverse solver performance in electrical impedance tomography (EIT). A MATLAB based boundary data simulator (BDS) is developed to generate accurate boundary data using neighbouring current pattern for assessing the EIT inverse solvers. Domain diameter, inhomogeneity number, inhomogeneity geometry (shape, size, and position), background conductivity, and inhomogeneity conductivity are all set as BDS input variables. Different sets of boundary data are generated by changing the input variables of the BDS, and resistivity images are reconstructed using electrical impedance tomography and diffuse optical tomography reconstruction software (EIDORS). Results show that the BDS generates accurate boundary data for different types of single or multiple objects which are efficient enough to reconstruct the resistivity images for assessing the inverse solver. It is noticed that for the BDS with 2048 elements, the boundary data for all inhomogeneities with a diameter larger than 13.3% of that of the phantom are accurate enough to reconstruct the resistivity images in EIDORS-2D. By comparing the reconstructed image with an original geometry made in BDS, it would be easier to study the inverse solver performance and the origin of the boundary data error can be identified. PMID- 27006910 TI - Preliminary Deformational Studies on a Finite Element Model of the Nasal Septum Reveals Key Areas for Septal Realignment and Reconstruction. AB - Background. With the current lack of clinically relevant classification methods of septal deviation, computer-generated models are important, as septal cartilage is indistinguishable on current imaging methods, making preoperative planning difficult. Methods. Three-dimensional models of the septum were created from a CT scan, and incremental forces were applied. Results. Regardless of the force direction, with increasing force, the septum first tilts (type I) and then crumples into a C shape (type II) and finally into an S shape (type III). In type I, it is important to address the dislocation in the vomer-ethmoid cartilage junction and vomerine groove, where stress is concentrated. In types II and III, there is intrinsic fracture and shortening of the nasal septum, which may be dislocated off the anterior nasal spine. Surgery aims to relieve the posterior buckling and dislocation, with realignment of the septum to the ANS and possible spreader grafts to buttress the fracture sites. Conclusion. By identifying clinically observable septal deviations and the areas of stress concentration and dislocation, a straighter, more stable septum may be achieved. PMID- 27006911 TI - Markerless Lung Tumor Motion Tracking by Dynamic Decomposition of X-Ray Image Intensity. AB - We propose a new markerless tracking technique of lung tumor motion by using an X ray fluoroscopic image sequence for real-time image-guided radiation therapy (IGRT). A core innovation of the new technique is to extract a moving tumor intensity component from the fluoroscopic image intensity. The fluoroscopic intensity is the superimposition of intensity components of all the structures passed through by the X-ray. The tumor can then be extracted by decomposing the fluoroscopic intensity into the tumor intensity component and the others. The decomposition problem for more than two structures is ill posed, but it can be transformed into a well-posed one by temporally accumulating constraints that must be satisfied by the decomposed moving tumor component and the rest of the intensity components. The extracted tumor image can then be used to achieve accurate tumor motion tracking without implanted markers that are widely used in the current tracking techniques. The performance evaluation showed that the extraction error was sufficiently small and the extracted tumor tracking achieved a high and sufficient accuracy less than 1 mm for clinical datasets. These results clearly demonstrate the usefulness of the proposed method for markerless tumor motion tracking. PMID- 27006912 TI - Extraction of Blood Vessels in Retinal Images Using Four Different Techniques. AB - A variety of blood vessel extraction (BVE) techniques exist in the literature, but they do not always lead to acceptable solutions especially in the presence of anomalies where the reported work is limited. Four techniques are presented for BVE: (1) BVE using Image Line Cross-Sections (ILCS), (2) BVE using Edge Enhancement and Edge Detection (EEED), (3) BVE using Modified Matched Filtering (MMF), and (4) BVE using Continuation Algorithm (CA). These four techniques have been designed especially for abnormal retinal images containing low vessel contrasts, drusen, exudates, and other artifacts. The four techniques were applied to 30 abnormal retinal images, and the success rate was found to be (95 to 99%) for CA, (88-91%) for EEED, (80-85%) for MMF, and (74-78%) for ILCS. Application of these four techniques to 105 normal retinal images gave improved results: (99-100%) for CA, (96-98%) for EEED, (94-95%) for MMF, and (88-93%) for ILCS. Investigations revealed that the four techniques in the order of increasing performance could be arranged as ILCS, MMF, EEED, and CA. Here we demonstrate these four techniques for abnormal retinal images only. ILCS, EEED, and CA are novel additions whereas MMF is an improved and modified version of an existing matched filtering technique. CA is a promising technique. PMID- 27006913 TI - Applying the Bispectral Analysis on Widespread Diffuse Cross-Frequency Interactive Effects. AB - The aim of this paper is applying the bispectral analysis on widespread diffuse cross-frequency interactive effects. The event-related potentials (ERPs) research method was used in this study and it could collect the widespread diffuse cross frequency from mild cognitive impairment (MCI) patients' brain wave. In this study, the brain wave data were collected from 12 MCI subjects, 12 healthy elderly, and 12 healthy young. The findings showed that the decreased interhemispheric coherence of 8.8 Hz for MCI compared with healthy elderly in the central-parietal cortex to respective surrounding sites and each MCI subject showed significantly widespread diffuse pattern of cross-frequency interactions in comparison with the healthy controls in the left central-parietal and right frontal. This study provides some explanation and suggestions for these findings. PMID- 27006914 TI - An Adaptive Control Method for Ros-Drill Cellular Microinjector with Low Resolution Encoder. AB - A novel control methodology which uses a low-resolution encoder is presented for a cellular microinjection technology called the Ros-Drill (rotationally oscillating drill). It is developed primarily for ICSI (intracytoplasmic sperm injection) operations, with the objective of generating a desired oscillatory motion at the tip of a micro glass pipette. It is an inexpensive setup, which creates high-frequency (higher than 500 Hz) and small-amplitude (around 0.2 deg) rotational oscillations at the tip of an injection pipette. These rotational oscillations enable the pipette to drill into cell membranes with minimum biological damage. Such a motion control procedure presents no particular difficulty when it uses sufficiently precise motion sensors. However, size, costs, and accessibility of technology to the hardware components severely constrain the sensory capabilities. Consequently, the control mission and the trajectory tracking are adversely affected. This paper presents two contributions: (a) a dedicated novel adaptive feedback control method to achieve a satisfactory trajectory tracking capability. We demonstrate via experiments that the tracking of the harmonic rotational motion is achieved with desirable fidelity; (b) some important analytical features and related observations associated with the controlled harmonic motion which is created by the low resolution feedback control structure. PMID- 27006915 TI - Enabling 3D-Liver Perfusion Mapping from MR-DCE Imaging Using Distributed Computing. AB - An MR acquisition protocol and a processing method using distributed computing on the European Grid Infrastructure (EGI) to allow 3D liver perfusion parametric mapping after Magnetic Resonance Dynamic Contrast Enhanced (MR-DCE) imaging are presented. Seven patients (one healthy control and six with chronic liver diseases) were prospectively enrolled after liver biopsy. MR-dynamic acquisition was continuously performed in free-breathing during two minutes after simultaneous intravascular contrast agent (MS-325 blood pool agent) injection. Hepatic capillary system was modeled by a 3-parameters one-compartment pharmacokinetic model. The processing step was parallelized and executed on the EGI. It was modeled and implemented as a grid workflow using the Gwendia language and the MOTEUR workflow engine. Results showed good reproducibility in repeated processing on the grid. The results obtained from the grid were well correlated with ROI-based reference method ran locally on a personal computer. The speed-up range was 71 to 242 with an average value of 126. In conclusion, distributed computing applied to perfusion mapping brings significant speed-up to quantification step to be used for further clinical studies in a research context. Accuracy would be improved with higher image SNR accessible on the latest 3T MR systems available today. PMID- 27006916 TI - Use of Molecular Dynamics for the Refinement of an Electrostatic Model for the In Silico Design of a Polymer Antidote for the Anticoagulant Fondaparinux. AB - Molecular dynamics (MD) simulations results are herein incorporated into an electrostatic model used to determine the structure of an effective polymer-based antidote to the anticoagulant fondaparinux. In silico data for the polymer or its cationic binding groups has not, up to now, been available, and experimental data on the structure of the polymer-fondaparinux complex is extremely limited. Consequently, the task of optimizing the polymer structure is a daunting challenge. MD simulations provided a means to gain microscopic information on the interactions of the binding groups and fondaparinux that would have otherwise been inaccessible. This was used to refine the electrostatic model and improve the quantitative model predictions of binding affinity. Once refined, the model provided guidelines to improve electrostatic forces between candidate polymers and fondaparinux in order to increase association rate constants. PMID- 27006917 TI - Empirical Evaluation of Visual Fatigue from Display Alignment Errors Using Cerebral Hemodynamic Responses. AB - The purpose of this study was to investigate the effect of stereoscopic display alignment errors on visual fatigue and prefrontal cortical tissue hemodynamic responses. We collected hemodynamic data and perceptual ratings of visual fatigue while participants performed visual display tasks on 8 ft * 6 ft NEC LT silver screen with NEC LT 245 DLP projectors. There was statistical significant difference between subjective measures of visual fatigue before air traffic control task (BATC) and after air traffic control task (ATC 3), (P < 0.05). Statistical significance was observed between left dorsolateral prefrontal cortex oxygenated hemoglobin (l DLPFC-HbO2), left dorsolateral prefrontal cortex deoxygenated hemoglobin (l DLPFC-Hbb), and right dorsolateral prefrontal cortex deoxygenated hemoglobin (r DLPFC-Hbb) on stereoscopic alignment errors (P < 0.05). Thus, cortical tissue oxygenation requirement in the left hemisphere indicates that the effect of visual fatigue is more pronounced in the left dorsolateral prefrontal cortex. PMID- 27006918 TI - Chondrocyte Behavior on Micropatterns Fabricated Using Layer-by-Layer Lift-Off: Morphological Analysis. AB - Cell patterning has emerged as an elegant tool in developing cellular arrays, bioreactors, biosensors, and lab-on-chip devices and for use in engineering neotissue for repair or regeneration. In this study, micropatterned surfaces were created using the layer-by-layer lift-off (LbL-LO) method for analyzing canine chondrocytes response to patterned substrates. Five materials were chosen based on our previous studies. These included: poly(dimethyldiallylammonium chloride) (PDDA), poly(ethyleneimine) (PEI), poly(styrene sulfonate) (PSS), collagen, and chondroitin sulfate (CS). The substrates were patterned with these five different materials, in five and ten bilayers, resulting in the following multilayer nanofilm architectures: (PSS/PDDA)5, (PSS/PDDA)10; (CS/PEI)4/CS, (CS/PEI)9/CS; (PSS/PEI)5, (PSS/PEI)10; (PSS/Collagen)5, (PSS/Collagen)10; (PSS/PEI)4/PSS, (PSS/PEI)9/PSS. Cell characterization studies were used to assess the viability, longevity, and cellular response to the configured patterned multilayer architectures. The cumulative cell characterization data suggests that cell viability, longevity, and functionality were enhanced on micropatterned PEI, PSS, collagen, and CS multilayer nanofilms suggesting their possible use in biomedical applications. PMID- 27006919 TI - The Effects of Laser Marking and Symbol Etching on the Fatigue Life of Medical Devices. AB - This paper examines the question;" does permanent laser marking affect the mechanical performance of a metallic medical component?" The literature review revealed the surprising fact that very little has been presented or studied even though intuition suggests that its effect could be detrimental to a component's fatigue life. A brief investigation of laser marking suggests that defects greater than 25 MUm are possible. A theoretical investigation further suggests that this is unlikely to cause issues with relation to fast fracture but is highly likely to cause fatigue life issues. An experimental investigation confirmed that laser marking reduced the fatigue life of a component. This combination of lines of evidence suggests, strongly, that positioning of laser marking is highly critical and should not be left to chance. It is further suggested that medical device designers, especially those related to orthopaedic implants, should consider the position of laser marking in the design process. They should ensure that it is in an area of low stress amplitude. They should also ensure that they investigate worst-case scenarios when considering the stress environment; this, however, may not be straightforward. PMID- 27006920 TI - A LabVIEW Platform for Preclinical Imaging Using Digital Subtraction Angiography and Micro-CT. AB - CT and digital subtraction angiography (DSA) are ubiquitous in the clinic. Their preclinical equivalents are valuable imaging methods for studying disease models and treatment. We have developed a dual source/detector X-ray imaging system that we have used for both micro-CT and DSA studies in rodents. The control of such a complex imaging system requires substantial software development for which we use the graphical language LabVIEW (National Instruments, Austin, TX, USA). This paper focuses on a LabVIEW platform that we have developed to enable anatomical and functional imaging with micro-CT and DSA. Our LabVIEW applications integrate and control all the elements of our system including a dual source/detector X-ray system, a mechanical ventilator, a physiological monitor, and a power microinjector for the vascular delivery of X-ray contrast agents. Various applications allow cardiac- and respiratory-gated acquisitions for both DSA and micro-CT studies. Our results illustrate the application of DSA for cardiopulmonary studies and vascular imaging of the liver and coronary arteries. We also show how DSA can be used for functional imaging of the kidney. Finally, the power of 4D micro-CT imaging using both prospective and retrospective gating is shown for cardiac imaging. PMID- 27006921 TI - A Hybrid Image Filtering Method for Computer-Aided Detection of Microcalcification Clusters in Mammograms. AB - The presence of microcalcification clusters (MCs) in mammogram is a major indicator of breast cancer. Detection of an MC is one of the key issues for breast cancer control. In this paper, we present a highly accurate method based on a morphological image processing and wavelet transform technique to detect the MCs in mammograms. The microcalcifications are firstly enhanced by using multistructure elements morphological processing. Then, the candidates of microcalcifications are refined by a multilevel wavelet reconstruction approach. Finally, MCs are detected based on their distributions feature. Experiments are performed on 138 clinical mammograms. The proposed method is capable of detecting 92.9% of true microcalcification clusters with an average of 0.08 false microcalcification clusters detected per image. PMID- 27006922 TI - Detection of Myoglobin with an Open-Cavity-Based Label-Free Photonic Crystal Biosensor. AB - The label-free detection of one of the cardiac biomarkers, myoglobin, using a photonic-crystal-based biosensor in a total-internal-reflection configuration (PC TIR) is presented in this paper. The PC-TIR sensor possesses a unique open optical microcavity that allows for several key advantages in biomolecular assays. In contrast to a conventional closed microcavity, the open configuration allows easy functionalization of the sensing surface for rapid biomolecular binding assays. Moreover, the properties of PC structures make it easy to be designed and engineered for operating at any optical wavelength. Through fine design of the photonic crystal structure, biochemical modification of the sensor surface, and integration with a microfluidic system, we have demonstrated that the detection sensitivity of the sensor for myoglobin has reached the clinically significant concentration range, enabling potential usage of this biosensor for diagnosis of acute myocardial infarction. The real-time response of the sensor to the myoglobin binding may potentially provide point-of-care monitoring of patients and treatment effects. PMID- 27006924 TI - Snakes with Coordinate Regeneration Technique: An Application to Retinal Disc Boundary Detection. AB - A modified snake method based on the novel idea of coordinate regeneration is presented and is tested on an object with complex concavities and on retinal images for locating the boundaries of optic discs, where the conventional snake methods fail. We have demonstrated that the use of conventional snake method with our proposed coordinate regeneration technique gives ultimate solution for finding the boundaries of complex objects. The proposed method requires a Gaussian blur of the object with a large kernel so that the snake can be initialised away from the object boundaries. In the second and third steps the blurring kernel size is reduced so that exact boundaries can be located. Coordinate regeneration is applied at each step which ultimately converges the snake (active contour) to exact boundaries. For complex objects like optic discs in retinal images, vessels act as snake distracters and some preimage processing is required before the proposed technique is applied. We are demonstrating this technique to find the boundary of optic discs in retinal images. In principle, this technique can be extended to find the boundary of any object in other modalities of medical imaging. Simulation results are presented to support the idea. PMID- 27006923 TI - Transplantation of Nonexpanded Adipose Stromal Vascular Fraction and Platelet Rich Plasma for Articular Cartilage Injury Treatment in Mice Model. AB - Stromal vascular fraction (SVF) combined with platelet-rich plasma (PRP) is commonly used in preclinical and clinical osteoarthritis as well as articular cartilage injury treatment. However, this therapy has not carefully evaluated the safety and the efficacy. This research aims to assess the safety and the efficacy of SVF combined with PRP transplantation. Ten samples of SVFs and PRPs from donors were used in this research. About safety, we evaluate the expression of some genes related to tumor formation such as Oct-4, Nanog, SSEA3, and SSEA4 by RT-PCR, flow cytometry, and tumor formation when injected in NOD/SCID mice. About efficacy, SVF was injected with PRP into murine joint that caused joint failure. The results showed that SVFs are negative with Oct-4, Nanog, SSEA-3, and SSEA-4, as well as they cannot cause tumors in mice. SVFs combined with PRP can improve the joint regeneration in mice. These results proved that SVFs combined with PRP transplantation is a promising therapy for articular cartilage injury treatment. PMID- 27006925 TI - Using Design of Experiments Methods for Assessing Peak Contact Pressure to Material Properties of Soft Tissue in Human Knee. AB - Contact pressure in the knee joint is a key element in the mechanisms of knee pain and osteoarthritis. Assessing the contact pressure in tibiofemoral joint is a challenging mechanical problem due to uncertainty in material properties. In this study, a sensitivity analysis of tibiofemoral peak contact pressure to the material properties of the soft tissue was carried out through fractional factorial and Box-Behnken designs. The cartilage was modeled as linear elastic material, and in addition to its elastic modulus, interaction effects of soft tissue material properties were added compared to previous research. The results indicated that elastic modulus of the cartilage is the most effective factor. Interaction effects of axial/radial modulus with elastic modulus of cartilage, circumferential and axial/radial moduli of meniscus were other influential factors. Furthermore this study showed how design of experiment methods can help designers to reduce the number of finite element analyses and to better interpret the results. PMID- 27006926 TI - Muscle Contributions to L4-5 Joint Rotational Stiffness following Sudden Trunk Flexion and Extension Perturbations. AB - The purpose of this study was to investigate the contribution of individual muscles (MJRSm) to total joint rotational stiffness (MJRST) about the lumbar spine's L4-5 joint prior to, and following, sudden dynamic flexion or extension perturbations to the trunk. We collected kinematic and surface electromyography (sEMG) data while subjects maintained a kneeling posture on a parallel robotic platform, with their pelvis constrained by a harness. The parallel robotic platform caused sudden inertial trunk flexion or extension perturbations, with and without the subjects being aware of the timing and direction. Prevoluntary muscle forces incorporating both short and medium latency neuromuscular responses contributed significantly to joint rotational stiffness, following both sudden trunk flexion and extension motions. MJRST did not change with perturbation direction awareness. The lumbar erector spinae were always the greatest contributor to MJRST. This indicates that the neuromuscular feedback system significantly contributed to MJRST, and this behaviour likely enhances joint stability following sudden trunk flexion and extension perturbations. PMID- 27006927 TI - Development of an Anatomically Realistic Forward Solver for Thoracic Electrical Impedance Tomography. AB - Electrical impedance tomography (EIT) has the potential to provide a low cost and safe imaging modality for clinically monitoring patients being treated with mechanical ventilation. Variations in reconstruction algorithms at different clinical settings, however, make interpretation of regional ventilation across institutions difficult, presenting the need for a unified algorithm for thoracic EIT reconstruction. Development of such a consensual reconstruction algorithm necessitates a forward model capable of predicting surface impedance measurements as well as electric fields in the interior of the modeled thoracic volume. In this paper, we present an anatomically realistic forward solver for thoracic EIT that was built based on high resolution MR image data of a representative adult. Accuracy assessment of the developed forward solver in predicting surface impedance measurements by comparing the predicted and observed impedance measurements shows that the relative error is within the order of 5%, demonstrating the ability of the presented forward solver in generating high fidelity surface thoracic impedance data for thoracic EIT algorithm development and evaluation. PMID- 27006928 TI - A Simple and Inexpensive Stereotactic Guidance Frame for MRI-Guided Brain Biopsy in Canines. AB - A magnetic resonance imaging (MRI) guided stereotactic system was developed to provide veterinarians a method to accomplish minimally invasive stereotactic brain biopsies and procedures involving the cerebrum in canines. While MR-guided procedures are prevalent for humans, they are less common in animal practices. The system was designed to minimize fabrication costs in an effort to make such procedures more accessible in the veterinary field. A frame constrained the head without the need for punctures and supported registration and guidance attachments. Location data for registration and relevant structures were selected by the clinician, and a reverse kinematic analysis program generated the settings of the stereotactic arch to guide a needle to the desired location. Phantom experiments and three cadaver trials showed an average targeting error of <3 mm using the system. PMID- 27006929 TI - Detect AD Patients by Using EEG Coherence Analysis. AB - The purpose of this study is to discriminate mild Alzheimer's disease (AD) patients from the normal aging. The EEG coherence was applied to analyze the data from auditory oddball paradigm to discriminate the differences of corticocortical connections between mild AD patients and healthy subjects. The results showed that the lower values of coherence were performed in mild AD patients than in the normal aging subjects, especially in theta band. The implications and suggestions are shown in this study. PMID- 27006930 TI - Assessment of Visual Reliance in Balance Control: An Inexpensive Extension of the Static Posturography. AB - Ability of humans to maintain balance in an upright stance and during movement activities is one of the most natural skills affecting everyday life. This ability progressively deteriorates with increasing age, and balance impairment, often aggravated by age-related diseases, can result in falls that adversely impact the quality of life. Falls represent serious problems of health concern associated with aging. Many investigators, involved in different science disciplines such as medicine, engineering, psychology, and sport, have been attracted by a research of the human upright stance. In a clinical practice, stabilometry based on the force plate is the most widely available procedure used to evaluate the balance. In this paper, we have proposed a low-cost extension of the conventional stabilometry by the multimedia technology that allows identifying potentially disturbing effects of visual sensory information. Due to the proposed extension, a stabilometric assessment in terms of line integral of center of pressure (COP) during moving scene stimuli shows higher discrimination power between young healthy and elderly subjects with supposed stronger visual reliance. PMID- 27006931 TI - A Structured Approach for Investigating the Causes of Medical Device Adverse Events. AB - Aim. Medical device-related adverse events are often ascribed to "device" or "operator" failure although there are more complex causes. A structured approach, viewing the device in its clinical context, is developed to assist in-depth investigations of the causes. Method. Medical device applications involve devices, clinical teams, patients, and supporting infrastructure. The literature was explored for investigations and approaches to investigations, particularly structured approaches. From this a conceptual framework of causes was developed based primarily on device and clinical team caring for the patient within a supporting infrastructure, each aspect having detailed subdivisions. The approach was applied to incidents from the literature and an anonymous incident database. Results. The approach identified and classified the underlying causes of incidents described in the literature, exploring the details of "device," "operator," or "infrastructure" failures. Applied to incident databases it suggested that causes differ between device types and identified the causes of device unavailability. Discussion. The structured approach enables digging deeper to uncover the wider causes rather than ascribing to device or user fault. It can assess global patterns of causes. It can help develop consistent terminology for describing and sharing information on the causes of medical device adverse events. PMID- 27006933 TI - Material Properties of the Mandibular Trabecular Bone. AB - The present paper introduces a numerical simulation aided, experimental method for the measurement of Young's modulus of the trabecular substance in the human mandible. Compression tests were performed on fresh cadaveric samples containing trabecular bone covered with cortical layer, thus avoiding the destruction caused by the sterilization, preservation, and storage and the underestimation of the stiffness resulting from the individual failure of the trabeculae cut on the surfaces. The elastic modulus of the spongiosa was determined by the numerical simulation of each compression test using a specimen specific finite element model of each sample. The received mandibular trabecular bone Young's modulus values ranged from 6.9 to 199.5 MPa. PMID- 27006934 TI - Quantitative Analysis of Diffusion Weighted MR Images of Brain Tumor Using Signal Intensity Gradient Technique. AB - The purpose of this study was to evaluate the role of diffusion weighted-magnetic resonance imaging (DW-MRI) in the examination and classification of brain tumors, namely, glioma and meningioma. Our hypothesis was that as signal intensity variations on diffusion weighted (DW) images depend on histology and cellularity of the tumor, analysing the signal intensity characteristics on DW images may allow differentiating between the tumor types. Towards this end the signal intensity variations on DW images of the entire tumor volume data of 20 subjects with glioma and 12 subjects with meningioma were investigated and quantified using signal intensity gradient (SIG) parameter. The relative increase in the SIG values (RSIG) for the subjects with glioma and meningioma was in the range of 10.08-28.36 times and 5.60-9.86 times, respectively, compared to their corresponding SIG values on the contralateral hemisphere. The RSIG values were significantly different between the subjects with glioma and meningioma (P < 0.01), with no overlap between RSIG values across the two tumors. The results indicate that the quantitative changes in the RSIG values could be applied in the differential diagnosis of glioma and meningioma, and their adoption in clinical diagnosis and treatment could be helpful and informative. PMID- 27006932 TI - Bioelectrical Impedance Methods for Noninvasive Health Monitoring: A Review. AB - Under the alternating electrical excitation, biological tissues produce a complex electrical impedance which depends on tissue composition, structures, health status, and applied signal frequency, and hence the bioelectrical impedance methods can be utilized for noninvasive tissue characterization. As the impedance responses of these tissue parameters vary with frequencies of the applied signal, the impedance analysis conducted over a wide frequency band provides more information about the tissue interiors which help us to better understand the biological tissues anatomy, physiology, and pathology. Over past few decades, a number of impedance based noninvasive tissue characterization techniques such as bioelectrical impedance analysis (BIA), electrical impedance spectroscopy (EIS), electrical impedance plethysmography (IPG), impedance cardiography (ICG), and electrical impedance tomography (EIT) have been proposed and a lot of research works have been conducted on these methods for noninvasive tissue characterization and disease diagnosis. In this paper BIA, EIS, IPG, ICG, and EIT techniques and their applications in different fields have been reviewed and technical perspective of these impedance methods has been presented. The working principles, applications, merits, and demerits of these methods has been discussed in detail along with their other technical issues followed by present status and future trends. PMID- 27006935 TI - A Review on Technical and Clinical Impact of Microsoft Kinect on Physical Therapy and Rehabilitation. AB - This paper reviews technical and clinical impact of the Microsoft Kinect in physical therapy and rehabilitation. It covers the studies on patients with neurological disorders including stroke, Parkinson's, cerebral palsy, and MS as well as the elderly patients. Search results in Pubmed and Google scholar reveal increasing interest in using Kinect in medical application. Relevant papers are reviewed and divided into three groups: (1) papers which evaluated Kinect's accuracy and reliability, (2) papers which used Kinect for a rehabilitation system and provided clinical evaluation involving patients, and (3) papers which proposed a Kinect-based system for rehabilitation but fell short of providing clinical validation. At last, to serve as technical comparison to help future rehabilitation design other sensors similar to Kinect are reviewed. PMID- 27006936 TI - A Digital Model to Simulate Effects of Bone Architecture Variations on Texture at Spatial Resolutions of CT, HR-pQCT, and MUCT Scanners. AB - The quantification of changes in the trabecular bone structure induced by musculoskeletal diseases like osteoarthritis, osteoporosis, rheumatoid arthritis, and others by means of a texture analysis is a valuable tool which is expected to improve the diagnosis and monitoring of a disease. The reaction of texture parameters on different alterations in the architecture of the fine trabecular network and inherent imaging factors such as spatial resolution or image noise has to be understood in detail to ensure an accurate and reliable determination of the current bone state. Therefore, a digital model for the quantitative analysis of cancellous bone structures was developed. Five parameters were used for texture analysis: entropy, global and local inhomogeneity, local anisotropy, and variogram slope. Various generic structural changes of cancellous bone were simulated for different spatial resolutions. Additionally, the dependence of the texture parameters on tissue mineralization and noise was investigated. The present work explains changes in texture parameter outcomes based on structural changes originating from structure modifications and reveals that a texture analysis could provide useful information for a trabecular bone analysis even at resolutions below the dimensions of single trabeculae. PMID- 27006937 TI - Image Segmentation and Analysis of Flexion-Extension Radiographs of Cervical Spines. AB - We present a new analysis tool for cervical flexion-extension radiographs based on machine vision and computerized image processing. The method is based on semiautomatic image segmentation leading to detection of common landmarks such as the spinolaminar (SL) line or contour lines of the implanted anterior cervical plates. The technique allows for visualization of the local curvature of these landmarks during flexion-extension experiments. In addition to changes in the curvature of the SL line, it has been found that the cervical plates also deform during flexion-extension examination. While extension radiographs reveal larger curvature changes in the SL line, flexion radiographs on the other hand tend to generate larger curvature changes in the implanted cervical plates. Furthermore, while some lordosis is always present in the cervical plates by design, it actually decreases during extension and increases during flexion. Possible causes of this unexpected finding are also discussed. The described analysis may lead to a more precise interpretation of flexion-extension radiographs, allowing diagnosis of spinal instability and/or pseudoarthrosis in already seemingly fused spines. PMID- 27006938 TI - Detection and Classification of Cancer from Microscopic Biopsy Images Using Clinically Significant and Biologically Interpretable Features. AB - A framework for automated detection and classification of cancer from microscopic biopsy images using clinically significant and biologically interpretable features is proposed and examined. The various stages involved in the proposed methodology include enhancement of microscopic images, segmentation of background cells, features extraction, and finally the classification. An appropriate and efficient method is employed in each of the design steps of the proposed framework after making a comparative analysis of commonly used method in each category. For highlighting the details of the tissue and structures, the contrast limited adaptive histogram equalization approach is used. For the segmentation of background cells, k-means segmentation algorithm is used because it performs better in comparison to other commonly used segmentation methods. In feature extraction phase, it is proposed to extract various biologically interpretable and clinically significant shapes as well as morphology based features from the segmented images. These include gray level texture features, color based features, color gray level texture features, Law's Texture Energy based features, Tamura's features, and wavelet features. Finally, the K-nearest neighborhood method is used for classification of images into normal and cancerous categories because it is performing better in comparison to other commonly used methods for this application. The performance of the proposed framework is evaluated using well-known parameters for four fundamental tissues (connective, epithelial, muscular, and nervous) of randomly selected 1000 microscopic biopsy images. PMID- 27006939 TI - Electrical Bioimpedance Analysis: A New Method in Cervical Cancer Screening. AB - Cervical cancer is the second most common female cancer worldwide and a disease of concern due to its high rate of incidence of about 500,000 women annually and is responsible for about 280,000 deaths in a year. The mortality and morbidity of cervical cancer are reduced through mass screening via Pap smear, but this technique suffers from very high false negativity of around 30% to 40% and hence the sensitivity of this technique is not more than 60%. Electrical bioimpedance study employing cytosensors over a frequency range offers instantaneous and quantitative means to monitor cellular events and is an upcoming technique in real time to classify cells as normal and abnormal ones. This technology is exploited for label-free detection of diseases by identifying and measuring nonbiological parameters of the cell which may carry the disease signature. PMID- 27006940 TI - Labview Based ECG Patient Monitoring System for Cardiovascular Patient Using SMTP Technology. AB - This paper leads to developing a Labview based ECG patient monitoring system for cardiovascular patient using Simple Mail Transfer Protocol technology. The designed device has been divided into three parts. First part is ECG amplifier circuit, built using instrumentation amplifier (AD620) followed by signal conditioning circuit with the operation amplifier (lm741). Secondly, the DAQ card is used to convert the analog signal into digital form for the further process. Furthermore, the data has been processed in Labview where the digital filter techniques have been implemented to remove the noise from the acquired signal. After processing, the algorithm was developed to calculate the heart rate and to analyze the arrhythmia condition. Finally, SMTP technology has been added in our work to make device more communicative and much more cost-effective solution in telemedicine technology which has been key-problem to realize the telediagnosis and monitoring of ECG signals. The technology also can be easily implemented over already existing Internet. PMID- 27006942 TI - Effects of 4-Week Intensive Active-Resistive Training with an EMG-Based Exoskeleton Robot on Muscle Strength in Older People: A Pilot Study. AB - This study aims to investigate the idea that an active-resistive training with an EMG-based exoskeleton robot could be beneficial to muscle strength and antagonist muscle cocontraction control after 4-week intensive elbow flexion/extension training. Three older people over 65 years participated the training for an hour per session and completed total 20 sessions during four weeks. Outcome measures were chosen as the maximum joint torque and cocontraction ratio between the biceps/triceps brachii muscles at pre-/post-training. The Wilcoxon signed-ranks test was performed to evaluate paired difference for the outcome measures. As a result, there was no significant difference in the maximum flexion or extension torque at pre- and post-training. However, the cocontraction ratio of the triceps brachii muscle as the antagonist was significantly decreased by 9.8% after the 4 week intensive training. The active-resistive training with the exoskeleton robot in the older people yielded a promising result, showing significant changes in the antagonist muscle cocontraction. PMID- 27006944 TI - Evaluating Religious Influences on the Utilization of Maternal Health Services among Muslim and Christian Women in North-Central Nigeria. AB - INTRODUCTION: Uptake of antenatal services is low in Nigeria; however, indicators in the Christian-dominated South have been better than in the Muslim-dominated North. This study evaluated religious influences on utilization of general and HIV-related maternal health services among women in rural and periurban North Central Nigeria. MATERIALS AND METHODS: Targeted participants were HIV-positive, pregnant, or of reproductive age in the Federal Capital Territory and Nasarawa. Themes explored were utilization of facility-based services, provider gender preferences, and Mentor Mother acceptability. Thematic and content approaches were applied to manual data analysis. RESULTS: Sixty-eight (68) women were recruited, 72% Christian and 28% Muslim. There were no significant religious influences identified among barriers to maternal service uptake. All participants stated preference for facility-based services. Uptake limitations were mainly distance from clinic and socioeconomic dependence on male partners rather than religious restrictions. Neither Muslim nor Christian women had provider gender preferences; competence and positive attitude were more important. All women found Mentor Mothers highly acceptable. CONCLUSION: Barriers to uptake of maternal health services appear to be minimally influenced by religion. ANC/PMTCT uptake interventions should target male partner buy-in and support, healthcare provider training to improve attitudes, and Mentor Mother program strengthening and impact assessment. PMID- 27006943 TI - Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review. AB - Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats. We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study. PMID- 27006941 TI - The Complex Relationship of Extracorporeal Membrane Oxygenation and Acute Kidney Injury: Causation or Association? AB - Extracorporeal membrane oxygenation (ECMO) is a modified cardiopulmonary bypass (CPB) circuit capable of providing prolonged cardiorespiratory support. Recent advancement in ECMO technology has resulted in increased utilisation and clinical application. It can be used as a bridge-to-recovery, bridge-to-bridge, bridge-to transplant, or bridge-to-decision. ECMO can restitute physiology in critically ill patients, which may minimise the risk of progressive multiorgan dysfunction. Alternatively, iatrogenic complications of ECMO clearly contribute to worse outcomes. These factors affect the risk : benefit ratio of ECMO which ultimately influence commencement/timing of ECMO. The complex interplay of pre-ECMO, ECMO, and post-ECMO pathophysiological processes are responsible for the substantial increased incidence of ECMO-associated acute kidney injury (EAKI). The development of EAKI significantly contributes to morbidity and mortality; however, there is a lack of evidence defining a potential benefit or causative link between ECMO and AKI. This area warrants investigation as further research will delineate the mechanisms involved and subsequent strategies to minimise the risk of EAKI. This review summarizes the current literature of ECMO and AKI, considers the possible benefits and risks of ECMO on renal function, outlines the related pathophysiology, highlights relevant investigative tools, and ultimately suggests an approach for future research into this under investigated area of critical care. PMID- 27006945 TI - Anticonvulsant and Toxicological Evaluation of Parafluorinated/Chlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide. AB - Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the pharmacotoxicological profile. We herein tested its fluorinated and chlorinated derivatives (F-HEPP and Cl-HEPP) with two seizure models, maximal electroshock seizures (MES), and intraperitoneal pentylenetetrazole (PTZ) administration. Neurotoxicity was examined via the rotarod test. With in silico methods, binding was probed on possible protein targets-GABAA receptors and the sodium channel Nav1.2. The median effective doses (ED50) of HEPP, F-HEPP, and Cl-HEPP in the MES seizure model were 129.6, 87.1, and 62.0 mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5 mg/kg. The HEPP-induced neurotoxic effect, which occurred at twice the ED50 against MES (p < 0.05), did not occur with F-HEPP or Cl-HEPP. Docking studies revealed that all tested ligands bound to GABAA receptors on a site near to the benzodiazepine binding site. However, on the sodium channel open pore Nav1.2, R HEPP had interactions similar to those reported for phenytoin, while its enantiomer and the ligands F-HEPP and Cl-HEPP reached a site that could disrupt the passage of sodium. Our results show that, as anticonvulsant agents, parahalogen substituted compounds have an advantageous pharmacotoxicological profile compared to their precursor. PMID- 27006946 TI - Serum Amyloid a Promotes Visfatin Expression in Macrophages. AB - Visfatin has been reported to exert an important role in the development of atherosclerosis. However, the mechanism that regulated the expression of Visfatin has not been elucidated yet. This study aimed to investigate the effect of SAA on the regulation of Visfatin, as well as the potential pathway. After RAW264.7 macrophages and primary monocytes were stimulated with SAA, the mRNA and protein expression of Visfatin was detected with real-time PCR and western blot, respectively. The concentration of Visfatin in the supernatant was measured with ELISA. Formyl peptide receptor 2 (FPR2) agonist (WKYMVm) and inhibitor (WRW(4)), extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (PD98059), and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist (Rosiglitazone) and inhibitor (GW9662) were used to investigate the mechanism of regulation of Visfatin. The results demonstrated that SAA upregulated Visfatin expression in cultured RAW264.7 macrophages and in the primary monocytes. WRW(4) decreased SAA-induced Visfatin production, while WKYMVm could induce Visfatin expression. PD98059 reduced SAA-induced Visfatin production. What is more, GW9662 inhibited SAA-induced Visfatin production, while Rosiglitazone promoted Visfatin expression. These results demonstrate that SAA upregulates Visfatin expression via a FPR2/ERK1/2/PPAR-gamma signaling pathway. PMID- 27006947 TI - The Protective Effects of 18beta-Glycyrrhetinic Acid on Helicobacter pylori Infected Gastric Mucosa in Mongolian Gerbils. AB - 18beta-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation related cytokines (IL-1beta, TNF-alpha, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 +/- 0.08 versus 3.17 +/- 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-alpha, IL 1beta, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug. PMID- 27006948 TI - Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis. AB - BACKGROUND: To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT) combined with gefitinib/erlotinib for treatment of brain metastases (BM) from non-small-cell lung cancer (NSCLC). METHODS: Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs) and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. RESULTS: A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35-3.47; P = 0.001), remission rate of central nervous system (OR = 6.06, 95% CI: 2.57-14.29; P < 0.0001), disease control rate (OR = 3.34, 95% CI: 1.84-6.07; P < 0.0001), overall survival (HR = 0.72, 95% CI: 0.58-0.89; P = 0.002), and 1-year survival rate (OR = 2.43, 95% CI: 1.51-3.91; P = 0.0002). In adverse events (III-IV), statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02-31.34; P = 0.003) and myelosuppression (OR = 0.19, 95% CI: 0.07-0.51; P = 0.0010). CONCLUSIONS: WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC. PMID- 27006949 TI - VGSC: A Web-Based Vector Graph Toolkit of Genome Synteny and Collinearity. AB - BACKGROUND: In order to understand the colocalization of genetic loci amongst species, synteny and collinearity analysis is a frequent task in comparative genomics research. However many analysis software packages are not effective in visualizing results. Problems include lack of graphic visualization, simple representation, or inextensible format of outputs. Moreover, higher throughput sequencing technology requires higher resolution image output. IMPLEMENTATION: To fill this gap, this paper publishes VGSC, the Vector Graph toolkit of genome Synteny and Collinearity, and its online service, to visualize the synteny and collinearity in the common graphical format, including both raster (JPEG, Bitmap, and PNG) and vector graphic (SVG, EPS, and PDF). RESULT: Users can upload sequence alignments from blast and collinearity relationship from the synteny analysis tools. The website can generate the vector or raster graphical results automatically. We also provide a java-based bytecode binary to enable the command line execution. PMID- 27006950 TI - Liver Stiffness Measurement in Psoriasis: Do Metabolic or Disease Factors Play the Important Role? AB - BACKGROUND: An increased prevalence of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) was reported in psoriasis. NAFLD can progress to nonalcoholic steatohepatitis and fibrosis. Transient elastography (TE) is a noninvasive liver fibrosis assessment. We evaluated the prevalence of significant liver fibrosis or high liver stiffness measurement (LSM) using the LSM cutoff over 7 kPa and its associated factors in psoriatic patients. METHODS: Subjects underwent TE and ultrasonography. Univariate and multivariate analysis were performed for the associated factors. RESULTS: One hundred and sixty-eight patients were recruited. Three patients were excluded due to TE failure. Mean BMI was 24.8 +/- 4.7 kg/m(2). NAFLD, metabolic syndrome, and diabetes were seen in 105 (63.6%), 83 (50.3%), and 31 (18.8%) patients. The total cumulative dose of methotrexate over 1.5 g was seen in 39 (23.6%) patients. Mean LSM was 5.3 +/- 2.9 kPa. High LSM was found in 18 (11.0%) patients. Waist circumference (OR: 1.24; 95% CI: 1.11-1.38; P = 0.0002), diabetes (OR: 12.70; 95% CI: 1.84-87.70; P = 0.010), and AST (OR: 1.08; 95% CI: 1.02-1.16; P = 0.017) were associated with high LSM. CONCLUSION: 11% of psoriatic patients had significant liver fibrosis by high LSM. Waist circumference, diabetes, and AST level were the independent predictors. PMID- 27006951 TI - Effect of Granulocyte-Colony Stimulating Factor on Endothelial Cells and Osteoblasts. AB - OBJECTIVES: Some animal studies showed that granulocyte-colony stimulating factor (G-CSF) provides beneficial environment for bone healing. It has been well documented that endothelial cells and osteoblasts play critical roles in multiple phases of bone healing. However, the biological effects of G-CSF on these cells remain controversial. This study aimed to investigate the influence of G-CSF at various concentrations on endothelial cells and osteoblasts. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) were treated with G-CSF at 1000, 100, 10, and 0 ng/mL, respectively. The capacity of cell proliferation, migration, and tube formation of HUVECs was evaluated at 72, 8, and 6 hours after treatment, respectively. The capacity of proliferation, differentiation, and mineralization of hOBs was evaluated at 24 hours, 72 hours, and 21 days after treatment, respectively. RESULTS: HUVECs treated with 100 and 1000 ng/mL G-CSF showed a significantly higher value comparing with controls in migration assay (p < 0.001, p < 0.01, resp.); the group treated with 1000 ng/mL G-CSF showed a significantly lower value on tube formation. No significant difference was detected in groups of hOBs. CONCLUSIONS: G-CSF showed favorable effects only on the migration of HUVECs, and no direct influence was found on hOBs. PMID- 27006952 TI - Novel Topics in Inflammatory Bowel Disease. PMID- 27006954 TI - Neutrophils: Their Role in Innate and Adaptive Immunity. PMID- 27006953 TI - Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes. AB - BACKGROUND: Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. METHODS: A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. RESULTS: Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). CONCLUSIONS: Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID- 27006955 TI - TLR Stimulation Dynamically Regulates Heme and Iron Export Gene Expression in Macrophages. AB - Pathogenic bacteria have evolved multiple mechanisms to capture iron or iron containing heme from host tissues or blood. In response, organisms have developed defense mechanisms to keep iron from pathogens. Very little of the body's iron store is available as free heme; rather nearly all body iron is complexed with heme or other proteins. The feline leukemia virus, subgroup C (FeLV-C) receptor, FLVCR, exports heme from cells. It was unknown whether FLVCR regulates heme-iron availability after infection, but given that other heme regulatory proteins are upregulated in macrophages in response to bacterial infection, we hypothesized that macrophages dynamically regulate FLVCR. We stimulated murine primary macrophages or macrophage cell lines with LPS and found that Flvcr is rapidly downregulated in a TLR4/MD2-dependent manner; TLR1/2 and TLR3 stimulation also decreased Flvcr expression. We identified several candidate TLR-activated transcription factors that can bind to the Flvcr promoter. Macrophages must balance the need to sequester iron from systemic circulating or intracellular pathogens with the macrophage requirement for heme and iron to produce reactive oxygen species. Our findings underscore the complexity of this regulation and point to a new role for FLVCR and heme export in macrophages responses to infection and inflammation. PMID- 27006957 TI - Intraoperative Tension Pneumothorax in a Patient With Remote Trauma and Previous Tracheostomy. AB - Many trauma patients present with a combination of cranial and thoracic injury. Anesthesia for these patients carries the risk of intraoperative hemodynamic instability and respiratory complications during mechanical ventilation. Massive air leakage through a lacerated lung will result in inadequate ventilation and hypoxemia and, if left undiagnosed, may significantly compromise the hemodynamic function and create a life-threatening situation. Even though these complications are more characteristic for the early phase of trauma management, in some cases, such a scenario may develop even months after the initial trauma. We report a case of a 25-year-old patient with remote thoracic trauma, who developed an intraoperative tension pneumothorax and hemodynamic instability while undergoing an elective cranioplasty. The intraoperative patient assessment was made even more challenging by unexpected massive blood loss from the surgical site. Timely recognition and management of intraoperative pneumothorax along with adequate blood replacement stabilized the patient and helped avoid an unfavorable outcome. This case highlights the risks of intraoperative pneumothorax in trauma patients, which may develop even months after injury. A high index of suspicion and timely decompression can be life saving in this type of situation. PMID- 27006956 TI - Colonic Mucosal Epigenome and Microbiome Development in Children and Adolescents. AB - Epigenetic and microbiome changes during pediatric development have been implicated as important elements in the developmental origins of inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC), which are linked to early onset colorectal cancer (CRC). Colonic mucosal samples from 22 control children between 3.5 and 17.5 years of age were studied by Infinium HumanMethylation450 BeadChips and, in 10 cases, by 454 pyrosequencing of the bacterial 16S rRNA gene. Intercalating age-specific DNA methylation and microbiome changes were identified, which may have significant translational relevance in the developmental origins of IBD and CRC. PMID- 27006958 TI - Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child: Case Report and Review of the Literature. AB - Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF) are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD) with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date. PMID- 27006959 TI - Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine. AB - Background. In this study, we analyzed the protective efficacy of a simian immunodeficiency virus (SIV) macaque 239 (SIVmac239) analogue of the clinically tested GOVX-B11 deoxyribonucleic acid (DNA)/modified vaccinia Ankara (MVA) human immunodeficiency virus vaccine. Methods. The tested vaccine used a DNA immunogen mutated to mimic the human vaccine and a regimen with DNA deliveries at weeks 0 and 8 and MVA deliveries at weeks 16 and 32. Twelve weekly rectal challenges with 0.3 animal infectious doses of SIV sootey mangabey E660 (SIVsmE660) were administered starting at 6 months after the last immunization. Results. Over the first 6 rectal exposures to SIVsmE660, <10-year-old tripartite motif-containing protein 5 (TRIM5)alpha-permissive rhesus macaques showed an 80% reduction in per exposure risk of infection as opposed to a 46% reduction in animals over 10 years old; and, over the 12 challenges, they showed a 72% as opposed to a 10% reduction. Analyses of elicited immune responses suggested that higher antibody responses in the younger animals had played a role in protection. Conclusions. The simian analogue of the GOVX-B11 HIV provided strong protection against repeated rectal challenges in young adult macaques. PMID- 27006960 TI - Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy. AB - Background. Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods. We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (>=F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results. The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (>=F3) decreased 12.3% (32.7%-20.4%) over a median of 31 months. Conclusions. The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression. PMID- 27006961 TI - A Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis. AB - Prolonged neutropenia is generally thought to be the major factor for invasive pulmonary aspergillosis (IPA). In the present study, we characterize the frequency, severity, and duration of neutropenia that immediately precedes IPA. Prolonged neutropenia was identified in only one third of all IPA cases and occurred exclusively in hematologic patients. PMID- 27006962 TI - Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab. AB - Presented is the first case of acute immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningoencephalitis in a patient on natalizumab for multiple sclerosis. The patient developed acute cerebral edema after initiation of amphotericin B. We propose several mechanisms that explain the acuity of IRIS in this specific patient population and suggest possible therapies. PMID- 27006963 TI - Rapid-Antigen Test Negative Malaria in a Traveler Returning From Thailand, Molecularly Diagnosed as Plasmodium knowlesi. AB - Plasmodium knowlesi has been identified in the last decade as a fifth species causing malaria in areas of South East Asia. Due to its short erythrocytic cycle, rapid development of high parasitemia and severe manifestations are frequently observed. Therefore, prompt diagnosis of infection is essential to prevent complications, but the low sensitivity of rapid diagnostic tests for P knowlesi pose a diagnostic challenge in acute settings. In this study, we report the case of a German traveler to Thailand, who was treated for P knowlesi malaria after returning to Germany. Rapid antigen test for malaria was negative on presentation. Diagnosis of a nonfalciparum malaria was made based on microscopy, and species definition was determined using polymerase chain reaction technique. PMID- 27006964 TI - A Missed Summer Wave of the 1918-1919 Influenza Pandemic: Evidence From Household Surveys in the United States and Norway. AB - Background. Reanalysis of influenza survey data from 1918 to 1919 was done to obtain new insights into the geographic and host factors responsible for the various waves. Methods. We analyzed the age- and sex-specific influenza morbidity, fatality, and mortality for the city of Baltimore and smaller towns and rural areas of Maryland and the city of Bergen (Norway), using survey data. The Maryland surveys captured the 1918 fall wave, whereas the Bergen survey captured 3 waves during 1918-1919. Results. Morbidity in rural areas of Maryland was higher than in the city of Baltimore during the fall of 1918, that was almost equal to that in Bergen during the summer of 1918. In Bergen, the morbidity in the fall was only half of that in the summer, with more females than males just above the age of 20 falling ill, as seen in both regions of Maryland. In contrast, more males than females fell ill during the summer wave in Bergen. Individuals <40 years had the highest morbidity, whereas school-aged children had the lowest fatality and mortality. Conclusion. A previously unrecognized pandemic summer wave may have hit the 2 regions of Maryland in 1918. PMID- 27006965 TI - Long-Term Control of Human Immunodeficiency Virus-1 Replication Despite Extensive Resistance to Current Antiretroviral Regimens: Clonal Analysis of Resistance Mutations in Proviral Deoxyribonucleic Acid. AB - Archived resistance mutations compromise antiretroviral treatment. We have investigated 3 selected aviremic patients who had extensive historical resistance to their current regimen. All 3 patients underwent unstructured treatment interruptions associated to the re-emergence of wild-type virus before starting their current suppressive regimes. Almost all historical resistance mutations detected in plasma were found in circulating proviral deoxyribonucleic acid. None of the clones analyzed was fully resistant to the current antiretroviral regimen. PMID- 27006966 TI - Application of Whole-Genome Sequencing to an Unusual Outbreak of Invasive Group A Streptococcal Disease. AB - Whole-genome analysis was applied to investigate atypical point-source transmission of 2 invasive group A streptococcal (GAS) infections. Isolates were serotype M4, ST39, and genetically indistinguishable. Comparison with MGAS10750 revealed nonsynonymous polymorphisms in ropB and increased speB transcription. This study demonstrates the usefulness of whole-genome analyses for GAS outbreaks. PMID- 27006967 TI - Absence of Pneumocystis jirovecii Colonization in Human Immunodeficiency Virus Infected Individuals With and Without Airway Obstruction and With Undetectable Viral Load. AB - Pneumocystis jirovecii colonization has been associated with non-acquired immune deficiency syndrome (AIDS) pulmonary comorbidity. We used spirometry to measure pulmonary function and analyzed oral wash specimens by quantitative polymerase chain reaction (PCR), targeting the large mitochondrial ribosomal subunit. For sensitivity control, a blinded subsample was subjected to touch-down PCRs, targeting both large and small ribosomal subunits and the major surface glycoprotein. Pneumocystis jirovecii deoxyribonucleic acid (DNA) was detected in 1 of 156 (95% confidence interval, .1%-3.5%) virologically suppressed human immunodeficiency virus (HIV)-infected individuals confirmed by all PCR methods. Thus, prevalence of P jirovecii colonization was low and unlikely to be a major cause of pulmonary comorbidity in this group of well treated HIV-infected individuals. PMID- 27006968 TI - Unnecessary Antibiotics for Acute Respiratory Tract Infections: Association With Care Setting and Patient Demographics. AB - Background. Up to 40% of antibiotics are prescribed unnecessarily for acute respiratory tract infections (ARTIs). We sought to define factors associated with antibiotic overprescribing of ARTIs to inform efforts to improve practice. Methods. We conducted a retrospective analysis of ARTI visits between 2006 and 2010 from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. Those surveys provide a representative sample of US visits to community-based physicians and to hospital-based emergency departments (EDs) and outpatient practices. Patient factors (age, sex, race, underlying lung disease, tobacco use, insurance), physician specialty, practice demographics (percentage poverty, median household income, percentage with a Bachelor's Degree, urban-rural status, geographic region), and care setting (ED, hospital, or community-based practice) were evaluated as predictors of antibiotic overprescribing for ARTIs. Results. Hospital and community-practice visits had more antibiotic overprescribing than ED visits (odds ratio [OR] = 1.64 and 95% confidence interval [CI], 1.27-2.12 and OR = 1.59 and 95% CI, 1.26-2.01, respectively). Care setting had significant interactions with geographic region and urban and rural location. The quartile with the lowest percentage of college educated residents had significantly greater overprescribing (adjusted OR = 1.41; 95% CI, 1.07-1.86) than the highest quartile. Current tobacco users were overprescribed more often than nonsmokers (OR = 1.71; 95% CI, 1.38-2.12). Patient age, insurance, and provider specialty were other significant predictors. Conclusions. Tobacco use and a lower grouped rate of college education were associated with overprescribing and may reflect poor health literacy. A focus on educating the patient may be an effective approach to stewardship. PMID- 27006969 TI - Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies. AB - Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD. PMID- 27006971 TI - Disrupted balance of T cells under natalizumab treatment in multiple sclerosis. AB - OBJECTIVE: To compare effects of natalizumab on inflammatory and regulatory T cells with regard to expression of alpha4-integrin (CD49d). METHODS: Twenty-seven natalizumab-naive and 8 natalizumab-treated patients with multiple sclerosis (MS), 7 patients with neuromyelitis optica (NMO) or NMO spectrum disorder, and 8 healthy controls were included. The positive rate of CD49d was analyzed and compared among T helper 1 (Th1), T helper 17 (Th17), and regulatory T (Treg) cells (CD49d+Th1, CD49d+Th17, and CD49d+Treg, respectively). RESULTS: Natalizumab treatment increased CD49d ratios, CD49d+Th1/CD49d+Treg, and CD49d+Th17/CD49d+Treg. This indicates larger reduction of the CD49d+ population in Treg cells than in Th1 or Th17 cells. The CD49d ratios of 2 patients who experienced exacerbation during natalizumab treatment were remarkably higher than those of the other natalizumab-treated patients. Natalizumab treatment increased the expression of TBX21, RORC, interferon (IFN)-gamma, and interleukin (IL)-17A, and decreased the expression of FOXP3 in CD49d+ memory CD4 T cells. Natalizumab treatment also increased the amount of IFN-gamma and IL-17A secreted by CD49d+ memory CD4 T cells. CONCLUSIONS: The reduction rate of the CD49d+ population in Treg cells was larger than that in Th1 or Th17 cells. Although the large reduction in CD49d+ population is beneficial for MS, the proinflammatory state of residual CD49d+ cells might, in part, explain the presence of disease activity under natalizumab treatment. PMID- 27006970 TI - All-in-one processing of heterogeneous human cell grafts for gene and cell therapy. AB - Current cell processing technologies for gene and cell therapies are often slow, expensive, labor intensive and are compromised by high cell losses and poor selectivity thus limiting the efficacy and availability of clinical cell therapies. We employ cell-specific on-demand mechanical intracellular impact from laser pulse-activated plasmonic nanobubbles (PNB) to process heterogeneous human cell grafts ex vivo with dual simultaneous functionality, the high cell type specificity, efficacy and processing rate for transfection of target CD3+ cells and elimination of subsets of unwanted CD25+ cells. The developed bulk flow PNB system selectively processed human cells at a rate of up to 100 million cell/minute, providing simultaneous transfection of CD3+ cells with the therapeutic gene (FKBP12(V36)-p30Caspase9) with the efficacy of 77% and viability 95% (versus 12 and 60%, respectively, for standard electroporation) and elimination of CD25+ cells with 99% efficacy. PNB flow technology can unite and replace several methodologies in an all-in-one universal ex vivo simultaneous procedure to precisely and rapidly prepare a cell graft for therapy. PNB's can process various cell systems including cord blood, stem cells, and bone marrow. PMID- 27006972 TI - Dimethyl fumarate treatment of relapsing-remitting multiple sclerosis influences B-cell subsets. AB - OBJECTIVE: To test the hypothesis that dimethyl fumarate (Tecfidera, BG-12) affects B-cell subsets in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Peripheral blood B cells were compared for surface marker expression in patients with RRMS prior to initiation of treatment, after 4-6 months, and at more than 1 year of treatment with BG-12. Production of interleukin (IL)-10 by RRMS patient B cells was also analyzed. RESULTS: Total numbers of peripheral blood B lymphocytes declined after 4-6 months of BG-12 treatment, due to losses in both the CD27+ memory B cells and CD27(neg) B-cell subsets. Some interpatient variability was observed. In contrast, circulating CD24(high)CD38(high) (T2-MZP) B cells increased in percentage in the majority of patients with RRMS after 4-6 months and were present in higher numbers in all of the patients after 12 months of treatment. The CD43+CD27+ B-1 B cells also increased at the later time point in most patients but were unchanged at 4-6 months compared to pretreatment levels. Purified B cells from 7 of the 9 patients with RRMS tested after 4-6 months of treatment were able to produce IL-10 following CD40 ligand stimulation, and the amount corresponded with the combined levels of T2-MZP and B-1 B cells in the sample. None of the patients with RRMS in this study have had a relapse while taking BG-12. CONCLUSIONS: These data suggest that BG-12 differentially affects B-cell subsets in patients with RRMS, resulting in increased numbers of circulating B lymphocytes with regulatory capacity. PMID- 27006973 TI - Early LPS-induced ERK activation in retinal pigment epithelium cells is dependent on PIP 2 -PLC. AB - This article presents additional data regarding the study "The phospholipase D pathway mediates the inflammatory response of the retinal pigment epithelium" [1]. The new data presented here show that short exposure of RPE cells to lipopolysaccharide (LPS) induces an early and transient activation of the extracellular signal-regulated kinase (ERK1/2). This early ERK1/2 activation is dependent on phosphatidylinositol bisphosphate-phospholipase C (PIP2-PLC). On the contrary, neither the phospholipase D 1 (PLD1) nor the PLD2 inhibition is able to modulate the early ERK1/2 activation induced by LPS in RPE cells. PMID- 27006974 TI - Data for stable formulation of steroid hormone receptor-targeted liposomes for cancer therapeutics. AB - A detailed description of steroid hormone ligand containing liposomes and their stability has been given. Liposomes were complexed with beta-gal DNA and used to transfect cancer and non-cancer cells. The stability of the liposomes and lipoplexes were analysed using dynamic light scattering and DNA-binding gel images. The formulations were used to assess the delivery of anticancer gene, p53 in cancer cells. The dataset consists of DNA-binding gel images, transfection, cytotoxicity and reverse transcriptase PCR images. PMID- 27006975 TI - Handwritten mathematical symbols dataset. AB - Due to the technological advances in recent years, paper scientific documents are used less and less. Thus, the trend in the scientific community to use digital documents has increased considerably. Among these documents, there are scientific documents and more specifically mathematics documents. In this context, we present our own dataset of handwritten mathematical symbols composed of 10,379 images. This dataset gathers Arabic characters, Latin characters, Arabic numerals, Latin numerals, arithmetic operators, set-symbols, comparison symbols, delimiters, etc. PMID- 27006976 TI - Access to Network Login by Three-Factor Authentication for Effective Information Security. AB - Today's technology development in the field of computer along with internet of things made huge difference in the transformation of our lives. Basic computer framework and web client need to make significant login signify getting to mail, long range interpersonal communication, internet keeping money, booking tickets, perusing online daily papers, and so forth. The login user name and secret key mapping validate if the logging user is the intended client. Secret key is assumed an indispensable part in security. The objective of MFA is to make a layered safeguard and make it more troublesome for an unauthenticated entity to get to an objective, for example, a physical area, processing gadget, system, or database. In the event that one element is bargained or broken, the assailant still has two more boundaries to rupture before effectively breaking into the objective. An endeavor has been made by utilizing three variable types of authentication. In this way managing additional secret key includes an additional layer of security. PMID- 27006977 TI - Design and Evaluation of a Proxy-Based Monitoring System for OpenFlow Networks. AB - Software-Defined Networking (SDN) has attracted attention along with the popularization of cloud environment and server virtualization. In SDN, the control plane and the data plane are decoupled so that the logical topology and routing control can be configured dynamically depending on network conditions. To obtain network conditions precisely, a network monitoring mechanism is necessary. In this paper, we focus on OpenFlow which is a core technology to realize SDN. We propose, design, implement, and evaluate a network monitoring system for OpenFlow networks. Our proposed system acts as a proxy between an OpenFlow controller and OpenFlow switches. Through experimental evaluations, we confirm that our proposed system can capture packets and monitor traffic information depending on administrator's configuration. In addition, we show that our proposed system does not influence significant performance degradation to overall network performance. PMID- 27006978 TI - A Survey on the Effect of Livestock Production System and Finishing Diet on Sensory Characteristics of Foal Meat Using Generalized Procrustes Analysis. AB - The influence of livestock production system [Freedom Extensive System (FES) versus Semi-Extensive System (SES)] and finishing feed (1.5 kg versus 3.0 kg of commercial feed in the finishing period) diet on sensory properties of foal meat using Generalized Procrustes Analysis (GPA) was studied. For this work, a total of 24 foals (8 from FES and 16 from SES) were used. Samples were evaluated by eight panelists for eight sensory attributes: colour, marbling, odour intensity, sweetness, springiness, hardness, chewiness, and juiciness. Data were analyzed using a GPA to minimize differences among testers. Highly appreciated sensory properties (odour intensity, red colour, marbling, and juiciness) were mostly associated with foals from the Semi-Extensive System. On the other hand, the three groups studied (FES, 1.5SES, and 3SES) were clearly recognized by panelists on the consensus configuration and they were clearly separated on the map. This study concluded that sensory characteristics of foal meat from a Semi-Extensive Production System with a finishing diet of 3 kg concentrate were more preferable than the other ones. PMID- 27006979 TI - Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats. AB - We performed experiments in cats with a spinal cord penetrating hemisection at T13-L1 level, with and without tamoxifen treatment. The results showed that the numbers of the ipsilateral and contralateral ventral horn neurons were reduced to less than half in the nontreated animals compared with the treated ones. Also, axons myelin sheet was preserved to almost normal values in treated cats. On the contrary, in the untreated animals, their myelin sheet was reduced to 28% at 30 days after injury (DAI), in both the ipsilateral and contralateral regions of the spinal cord. Additionally, we made hindlimb kinematics experiments to study the effects of tamoxifen on cat locomotion after the injury: at 4, 16, and 30 DAI. We observed that the ipsilateral hindlimb angular displacement (AD) of the pendulum like movements (PLM) during gait locomotion was recovered to almost normal values in treated cats. Contralateral PLM acquired similar values to those obtained in intact cats. At 4 DAI, untreated animals showed a compensatory increment of PLM occurring in the contralateral hindlimb, which was partially recovered at 30 DAI. Our findings indicate that tamoxifen exerts a neuroprotective effect and preserves or produces myelinated axons, which could benefit the locomotion recovery in injured cats. PMID- 27006981 TI - Response to Letter. PMID- 27006980 TI - Synthesis and catalytic activity of heteroatom doped metal-free single-wall carbon nanohorns. AB - Boron-, phosphorus-, nitrogen-doped and co-doped single-wall carbon nanohorns were produced using an arc-vaporization method. These as-prepared doped materials consist of uniform isolated nanohorns and exhibit greatly enhanced catalytic capabilities in the reduction reaction of nitrobenzene and a volcano-shape trend between their activities with a B dopant content is found. Moreover, the B-C3 and P-C3 species in doped nanohorns might act as the acidic and basic sites to promote this reaction. PMID- 27006982 TI - [Acoustic impedanceometry: the evolution of diagnostic possibilities]. AB - The present review of the literature reports the materials concerning the application of the acoustic impedance measurements of normal ears and pathologically charged organs of hearing that are important for the differential diagnostics and monitoring of the hearing system condition during the conservative and surgical treatment. PMID- 27006983 TI - [The clinical aspects of occupational sensorineural impairment of hearing of the acoustic origin]. AB - The objective of the present study was to elucidate the specific clinical features of occupational sensorineural impairment of hearing (OSNHI) depending on the origin of this pathology, viz. noise, infrasound and/or their combination. The review of research concerning this problem made it possible to systematize variants of ODNHI based on the clinical signs taking into consideration the influence of these physical factors. Pathophysiological features of the exposure of the organs of hearing to infrasound are described. PMID- 27006984 TI - [The hearing function in the premature infants]. AB - The present review of the literature is focused on the morphological and functional aspects of antenatal ontogenesis of the hearing system with special reference to the peculiar features of its formation during the post-natal period in the premature infants. In this context, the results of the objective psychoacoustic investigation s are considered (including those obtained by such methods as threshold audiometry, verbal and non-verbal tests, evaluation of central auditory processing of the sound information). Also presented are the results of the objective methods of hearing investigations (acoustic impedancometry, registration of optoacoustic emission and auditory evoked potentials). The underdevelopment of the hearing system in the premature infants manifests itself as the specific functional features of all its components. Their parameters are presented with reference to dynamics of their formation. In addition, the problem of central auditory processing of the disorders that are very likely to be present in the premature infants are discussed. PMID- 27006986 TI - [The etiopathogenetic aspects of sensorineural impairment of hearing]. AB - The author presents a review of the Russian- and foreign-language literature concerning etiology and pathogenesis of sensorineural hearing impairment with the opinions of domestic and foreign researches on this issue. PMID- 27006987 TI - Bridging the Silos of Service Delivery for High-Need, High-Cost Individuals. AB - Health care reform efforts that emphasize value have increased awareness of the importance of nonmedical factors in achieving better care, better health, and lower costs in the care of high-need, high-cost individuals. Programs that care for socioeconomically disadvantaged, high-need, high-cost individuals have achieved promising results in part by bridging traditional service delivery silos. This study examined 5 innovative community-oriented programs that are successfully coordinating medical and nonmedical services to identify factors that stimulate and sustain community-level collaboration and coordinated care across silos of health care, public health, and social services delivery. The authors constructed a conceptual framework depicting community health systems that highlights 4 foundational factors that facilitate community-oriented collaboration: flexible financing, shared leadership, shared data, and a strong shared vision of commitment toward delivery of person-centered care. PMID- 27006985 TI - A systematic review of the emerging definition of 'deprescribing' with network analysis: implications for future research and clinical practice. AB - AIMS: The aim of this study was to identify what definitions have been published for the term 'deprescribing', and determine whether a unifying definition could be reached. A secondary aim was to uncover patterns between the published definitions which could explain any variation. METHODS: Systematic literature searches were performed (earliest records to February 2014) in MEDLINE, Embase, CINAHL, Informit, Scopus and Google Scholar. The terms deprescrib* or de prescrib* were employed as a keyword search in all fields. Conventional content analysis and word frequencies were used to identify characteristics of the definitions. Network analysis was conducted to visualize characteristic distribution across authors and articles. RESULTS: Following removal of duplicates, 231 articles were retrieved, 37 of which included a definition. Eight characteristics of the definitions were identified: use of the term stop/withdraw/cease/discontinue (35 articles), aspect of prescribing included e.g. long term therapy/inappropriate medications (n = 18), use of the term 'process' or 'structured' (n = 13), withdrawal is planned/supervised/judicious (n = 11), involving multiple steps (n = 7), includes dose reduction/substitution (n = 7), desired goals/outcomes described (n = 5) and involves tapering (n = 4). Network analysis did not reveal patterns responsible for variations in previously used definitions. CONCLUSIONS: These findings show that there is lack of consensus on the definition of deprescribing. This article proposes the following definition: 'Deprescribing is the process of withdrawal of an inappropriate medication, supervised by a health care professional with the goal of managing polypharmacy and improving outcomes'. This definition has not yet been externally validated and further work is required to develop an internationally accepted and appropriate definition. PMID- 27006988 TI - ["My Home, my Car, my Boat" - Satisfaction with One's Own Standard of Living as a Predictor of Gender-Specific Mortality]. AB - BACKGROUND: Men have a higher risk of mortality than women and react much more sensitively to status-related stressors. The relationship between hierarchical rank and health, mediated on the HPA axis, delivers possible explanations for the more pronounced male sensitivity. In this context, the construct of status unease has attracted a lot of attention in recent years. It links social comparison with a reduced general wellbeing and considers it to be a major risk factor for various diseases. METHODS: An analysis of secondary data from the Socio-Economic Panel (SOEP) was used to analyze the extent to which subjective dissatisfaction with one's own standard of living is associated with an increased gender-related mortality risk. The statistical modeling of the question was carried out by performing gender-disaggregated Cox proportional hazard models. The unbalanced sub-sample consisted of 6 454 men (685 deaths) and 6 908 women (618 deaths). RESULTS: Dissatisfaction with one's standard of living has a significant influence on the mortality risk of men but not women: Men with low satisfaction have nearly a twice as high risk of mortality than the reference group (HR=1,95, 95% CI 1,48-2,58), men with moderate satisfaction a 25% higher mortality risk (HR=1,26, 95% CI 1,08-1,49). Furthermore, subjective status shows stronger dose response relationships than objective status parameters. CONCLUSION: Dissatisfaction with one's standard of living turns out to be a clear predictor for male mortality. Stress reactions due to disparaging social comparison processes triggered by the HPA-axis could be a central cause. The results indicate that the standardized inclusion of subjective status indicators should be considered in social-epidemiological analysis. The distinctive gender difference also points out that gender-sensitive epidemiological data analysis is reasonable. PMID- 27006989 TI - [Communication with Migrant Patients and their Parents in Inpatient General Pediatric Care]. AB - OBJECTIVES: Depending on the ethnic background of patients, the quality of communication between the parents of pediatric patients and clinicians, as well as the type and frequency of interpreter services was studied in an inpatient setting. METHODS: As part of a questionnaire-based survey, data from parents, doctors and nurses with reference to 220 pediatric patients treated in the Department of Pediatrics at the University Hospital Leipzig from February to May 2013 were analyzed; 18,2% of patients were migrants. RESULTS: No differences were found in the assessment of the quality of communication with clinic staff by migrant and non-migrant parents. Physicians as well as nurses rated the communication with migrant parents compared to non-migrant parents significantly lower. In up to 19,2% (data provided by nursing staff) and 15,3% (data provided by doctors) of the cases characterized by insufficient language skills on the part of migrant parents, interpreter services had to be procured. No professional interpreters were used. CONCLUSION: The results highlight once more the difficulties in communication between clinicians and migrant patients with insufficient language skills. More attention should be paid to the impact of the use of professional interpreters in the health care services. PMID- 27006990 TI - [Implementation of Workplace Health Promotion/Workplace Health Management in Germany: State-of-the Art and Need for Further Research]. AB - AIM: The data on health management programmes in German companies show quite heterogeneous results. The aim of the study was to gain more transparency into the cause of these discrepancies as well as information on factors influencing the willingness of companies to implement such programmes. METHODS: Based on a systematic database search, relevant studies were identified and comparative analysis of their contents was carried out. RESULTS: The existing studies on the health management programmes in German companies reveal significant discrepancies in terms of their research question, representativeness, approach and design. Nevertheless, they do reveal certain trends identifying significant factors that influence the willingness of companies to implement such programmes. CONCLUSION: In the design of future studies to analyse the distribution of corporate health management programmes, there is a need to agree on common definitions and data collection methods and how the results are to be categorised. When evaluating the effects of corporate programmes, the quantitative data would need to be supplemented with qualitative data that would be capable of identifying how such programmes are implemented and the associated organisation-specific cultural patterns. PMID- 27006991 TI - Unexpected Discovery of Dichloroacetate Derived Adenosine Triphosphate Competitors Targeting Pyruvate Dehydrogenase Kinase To Inhibit Cancer Proliferation. AB - Pyruvate dehydrogenase kinases (PDKs) have recently emerged as an attractive target for cancer therapy. Herein, we prepared a series of compounds derived from dichloroacetate (DCA) which inhibited cancer cells proliferation. For the first time, we have successfully developed DCA derived inhibitors that preferentially bind to the adenosine triphosphate (ATP) pocket of PDK isoform 1 (PDK1). PMID- 27006992 TI - Editorial: Mathematical modeling of infectious disease dynamics. PMID- 27006993 TI - Corrigendum. AB - ARTICLE TITLE: Go in for the kill: How plants deploy effector-triggered immunity to combat pathogens. AUTHORS: Liang Wu, Huan Chen, Chad Curtis, and Zheng Qing Fu. JOURNAL: Virulence. BIBLIOMETRICS: Volume 5, Issue 7, pages 710 721DOI:10.4161/viru.29755. The second half of the title appeared incorrectly as a subtitle in the print and online versions. The corrected title should appear as: "Go in for the kill: How plants deploy effector-triggered immunity to combat pathogens". The title has been updated in the online publication. The authors apologize for any inconvenience caused. PMID- 27006995 TI - Single-Particle Plasmon Voltammetry (spPV) for Detecting Anion Adsorption. AB - Nanoparticle and thin film surface plasmons are highly sensitive to electrochemically induced dielectric changes. We exploited this sensitivity to detect reversible electrochemical potential-driven anion adsorption by developing single-particle plasmon voltammetry (spPV) using plasmonic nanoparticles. spPV was used to detect sulfate electroadsorption to individual Au nanoparticles. By comparing both semiconducting and metallic thin film substrates with Au nanoparticle monomers and dimers, we demonstrated that using Au film substrates improved the signal in detecting sulfate electroadsorption and desorption through adsorbate modulated thin film conductance. Using single-particle surface plasmon spectroscopic techniques, we constructed spPV to sense sulfate, acetate, and perchlorate adsorption on coupled Au nanoparticles. spPV extends dynamic spectroelectrochemical sensing to the single-nanoparticle level using both individual plasmon resonance modes and total scattering intensity fluctuations. PMID- 27006999 TI - Black Anatase Titania with Ultrafast Sodium-Storage Performances Stimulated by Oxygen Vacancies. AB - Nanostructured black anatase titania with oxygen vacancies (OVs) is efficiently obtained and employed as an anode in sodium-ion batteries (SIBs) for the first time. The incorporation of OVs into TiO2 is demonstrated to render considerably enhanced-rate performances, higher initial capacities, and an accelerated electrochemical activation process during cycling, derived from the boosted intrinsic electric conductivity and improved kinetics of Na uptake. Bestowed with the integrated merits of OVs and shortened Na ion diffusion length in the nanostructure, black titania delivers a reversible specific capacity of 207.6 mAh g(-1) at 0.2 C, retains 99.1% over 500 cycles at 1 C stably, and still maintains 91.2 mAh g(-1) even at the high rate of 20 C. Density functional theory (DFT) calculations suggest that the lower sodiation energy barrier of anatase with OVs enables a more favorable Na intercalation into black anatase. Thus, it is of great significance to introduce OVs into TiO2 to stimulate ultrafast and durable sodium-storage properties, which also offers a potential strategy to project more superior electrodes, utilizing internal defects. PMID- 27006994 TI - Exosomes Derived from Squamous Head and Neck Cancer Promote Cell Survival after Ionizing Radiation. AB - Exosomes are nanometer-sized extracellular vesicles that are believed to function as intercellular communicators. Here, we report that exosomes are able to modify the radiation response of the head and neck cancer cell lines BHY and FaDu. Exosomes were isolated from the conditioned medium of irradiated as well as non irradiated head and neck cancer cells by serial centrifugation. Quantification using NanoSight technology indicated an increased exosome release from irradiated compared to non-irradiated cells 24 hours after treatment. To test whether the released exosomes influence the radiation response of other cells the exosomes were transferred to non-irradiated and irradiated recipient cells. We found an enhanced uptake of exosomes isolated from both irradiated and non-irradiated cells by irradiated recipient cells compared to non-irradiated recipient cells. Functional analyses by exosome transfer indicated that all exosomes (from non irradiated and irradiated donor cells) increase the proliferation of non irradiated recipient cells and the survival of irradiated recipient cells. The survival-promoting effects are more pronounced when exosomes isolated from irradiated compared to non-irradiated donor cells are transferred. A possible mechanism for the increased survival after irradiation could be the increase in DNA double-strand break repair monitored at 6, 8 and 10 h after the transfer of exosomes isolated from irradiated cells. This is abrogated by the destabilization of the exosomes. Our results demonstrate that radiation influences both the abundance and action of exosomes on recipient cells. Exosomes transmit prosurvival effects by promoting the proliferation and radioresistance of head and neck cancer cells. Taken together, this study indicates a functional role of exosomes in the response of tumor cells to radiation exposure within a therapeutic dose range and encourages that exosomes are useful objects of study for a better understanding of tumor radiation response. PMID- 27007000 TI - Implementation of rapid HIV and HCV testing within harm reduction programmes for people who inject drugs: a pilot study. AB - Including HCV and HIV rapid tests in harm reduction programmes (HRP) for people who inject drugs (PWID) can increase detection of these infections in high-risk populations who do not seek conventional health care. AIMS: To assess acceptability and feasibility of rapid HIV and HCV tests in HRP; to identify HIV and HCV prevalence rates in HRP; to identify the percentage of PWID with a reactive test that attend hospital for confirmation and follow-up. Rapid oral tests for HCV and HIV were offered to users of 13 HRP from both mobile units and facility-based centres. A total of 172 HCV and 198 HIV tests were performed, with a refusal rate of 1.7% and 10.4%, respectively. Injectors made up 64.9% of all drug users and 35.1% did not inject drugs. Overall, 20.3% of HCV tests and 2.5% of HIV test were reactive. Only 24 of the 35 reactive HCV could be confirmed (68.6%) and one was false-negative. Of the five HIV reactive cases, only two could be confirmed (40%) with 1 false-positive case. Acceptability of rapid HIV and HCV tests among HRP users was high. The usefulness of oral rapid tests in HRP has been demonstrated, especially in mobile HRP. PMID- 27007001 TI - Can preferences in information processing aid in understanding suicide risk among emerging adults? AB - The present study evaluated emerging adult (n = 192 college students) preferences in information processing (PIP), defined by the need for affect (NFA) and need for cognition (NFC), as they may be associated with suicide risk. The following were direct indicators of elevated suicide risk: presence of lifetime exposure to suicide (i.e., lifetime yes/no), elevated depressive symptoms, and greater NFA avoidance. Two different interactions resulted in elevated suicide risk: high depressive symptoms and high NFA avoidance, and high NFC and high NFA. Present results concerning PIP hold the potential to inform suicide risk assessment and prevention efforts among young adults. PMID- 27007002 TI - Five-Year Survival Data Demonstrating Durable Responses From a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma. PMID- 27007003 TI - Post Transplant Outcome of a Multicenter Phase II Study of Brentuximab Vedotin as First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT. PMID- 27007004 TI - Targeted BEACOPP Variants in Patients With Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma: Final Analysis of a Randomized Phase II Study. PMID- 27007005 TI - TARC Predicts PET-Normalization and Event Free Survival in Relapsed/Refractory Hodgkin Lymphoma Patients Treated With Brentuximab Vedotin. PMID- 27007006 TI - Brentuximab Vedotin in Combination With Dacarbazine or Bendamustine for Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years and Above: Interim Results of a Multi-Cohort Phase 2 Study. PMID- 27007007 TI - Randomized Phase 2 Open-Label Study of R-CHOP +/- Bortezomib in Patients (Pts) With Untreated Non-Germinal Center B-Cell-like (Non-GCB) Subtype Diffuse Large Cell Lymphoma (DLBCL): Results From the Pyramid Trial (NCT00931918). PMID- 27007008 TI - Updated Efficacy and Safety Data From the AETHERA Trial of Consolidation With Brentuximab Vedotin After Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse. PMID- 27007009 TI - Highlights in Lymphoma From the 2015 ASH Meeting: Commentary. PMID- 27007010 TI - First Multicenter, Randomized Phase 3 Study in Patients (Pts) With Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL): Alisertib (MLN8237) Versus Investigator's Choice (LUMIERE trial; NCT01482962). PMID- 27007011 TI - Temperature-Dependent Conformational Properties of Human Neuronal Calcium Sensor 1 Protein Revealed by All-Atom Simulations. AB - Neuronal calcium sensor-1 (NCS-1) protein has orthologues from Saccharomyces cerevisiae to human with highly conserved amino acid sequences. NCS-1 is an important factor controlling the animal's response to temperature change. This leads us to investigate the temperature effects on the conformational dynamics of human NCS-1 at 310 and 316 K by all-atom molecular dynamics (MD) simulations and dynamic community network analysis. Four independent 500 ns MD simulations show that secondary structure content at 316 K is similar to that at 310 K, whereas the global protein structure is expanded. Loop 3 (L3) adopts an extended state occuping the hydrophobic crevice, and the number of suboptimal communication paths between residue D176 and V190 is reduced at 316 K. The dynamic community network analysis suggests that the interdomain correlation is weakened, and the intradomain coupling is strengthened at 316 K. The elevated temperature reduces the number of the salt bridges, especially in C-domain. This study suggests that the elevated temperature affects the conformational dynamics of human NCS-1 protein. Comparison of the structural dynamics of R102Q mutant and Delta176-190 truncated NCS-1 suggests that the structural and dynamical response of NCS-1 protein to elevated temperature may be one of its intrinsic functional properties. PMID- 27007012 TI - Understanding Culture and Its Influence on HIV/AIDS-Related Communication Among Minority Men Who Have Sex With Men. AB - Scholarly research and government surveillance reports demonstrate that African American and Latino men who have sex with men (MSM) bear an inequitable burden of new HIV infections. Among the estimated 31,896 HIV infections attributed to male to-male sexual contact in 2011, approximately 62% occurred in African American (38.2%) and Latino (23.5) MSM. Simultaneously, recent scholarship on minority MSM and HIV/AIDS reports a dearth of qualitative communication research that address this health issue. This manuscript reports a research study that seeks to fill this gap in health communication theory and praxis. Through in-depth interviews with 17 MSM of color, this article draws upon the culture-centered approach to demonstrate how cultural and contextual nuances, (in)access to structural resources, and participants' agentive capacity to act upon available knowledge/resources influences the ways they manage (the threat of) HIV/AIDS. PMID- 27007013 TI - The effect of respiratory induced density variations on non-TOF PET quantitation in the lung. AB - Accurate PET quantitation requires a matched attenuation map. Obtaining matched CT attenuation maps in the thorax is difficult due to the respiratory cycle which causes both motion and density changes. Unlike with motion, little attention has been given to the effects of density changes in the lung on PET quantitation. This work aims to explore the extent of the errors caused by pulmonary density attenuation map mismatch on dynamic and static parameter estimates. Dynamic XCAT phantoms were utilised using clinically relevant (18)F-FDG and (18)F-FMISO time activity curves for all organs within the thorax to estimate the expected parameter errors. The simulations were then validated with PET data from 5 patients suffering from idiopathic pulmonary fibrosis who underwent PET/Cine-CT. The PET data were reconstructed with three gates obtained from the Cine-CT and the average Cine-CT. The lung TACs clearly displayed differences between true and measured curves with error depending on global activity distribution at the time of measurement. The density errors from using a mismatched attenuation map were found to have a considerable impact on PET quantitative accuracy. Maximum errors due to density mismatch were found to be as high as 25% in the XCAT simulation. Differences in patient derived kinetic parameter estimates and static concentration between the extreme gates were found to be as high as 31% and 14%, respectively. Overall our results show that respiratory associated density errors in the attenuation map affect quantitation throughout the lung, not just regions near boundaries. The extent of this error is dependent on the activity distribution in the thorax and hence on the tracer and time of acquisition. Consequently there may be a significant impact on estimated kinetic parameters throughout the lung. PMID- 27007014 TI - Biomarkers, bioindicators, molecular imaging, functional imaging, precision medicine, and the search for intelligent life in the universe. PMID- 27007015 TI - Question About the Analysis of Missing Data and Identification of an Error. PMID- 27007016 TI - Correction: New synthesis of phenyl-isothiocyanate C-functionalised cyclams. Bioconjugation and (64)Cu phenotypic PET imaging studies of multiple myeloma with the te2a derivative. AB - Correction for 'New synthesis of phenyl-isothiocyanate C-functionalised cyclams. Bioconjugation and 64Cu phenotypic PET imaging studies of multiple myeloma with the te2a derivative' by Zakaria Halime et al., Org. Biomol. Chem., 2015, 13, 11302-11314. PMID- 27007017 TI - Arabidopsis thalianaMRE11 is essential for activation of cell cycle arrest, transcriptional regulation and DNA repair upon the induction of double-stranded DNA breaks. AB - Given the fundamental role of MRE11 in many aspects of DNA metabolism and signalling in eukaryotes, we analysed the impact of several MRE11 mutations on DNA damage response (DDR) and DNA repair in Arabidopsis thaliana. Three different atmre11 and an atatm-2 mutant lines, together with the wild type (WT), were compared using a new Arabidopsis genotoxic assay for in situ evaluation of genome integrity and DNA damage repair efficiency after double strand break (DSB) induction. The results showed that, despite the phenotypic differences and different lengths of the putative truncated AtMRE11 proteins, all three atmre11 and the atatm-2 mutant lines exhibited common hypersensitivity to bleomycin treatment, where they only slightly reduced mitotic activity, indicating a G2/M checkpoint abrogation. In contrast to the WT, which reduced the frequency of chromosomal aberrations throughout the recovery period after treatment, none of the three atmre11 and atatm-2 mutants recovered. Moreover, atmre11-3 mutants, similarly to atatm-2 mutants, failed to transcriptionally induce several DDR genes and had altered expression of the CYCB1;1::GUS protein. Nevertheless, numerous chromosomal fusions in the atmre11 mutants, observed after DNA damage induction, suggest intensive DNA repair activity. These results indicate that functional and full-length AtMRE11 is essential for activation of the cell cycle arrest, transcriptional regulation and DNA repair upon induction of DSB. PMID- 27007019 TI - Tongue cancer in the young. PMID- 27007018 TI - Effect of a Perioperative Nutritional Supplementation with Oral Impact(r) in Patients undergoing Hepatic Surgery for Liver Cancer: A Prospective, Placebo Controlled, Randomized, Double-Blind Study. AB - Perioperative nutrition with supplements containing L-arginine, omega3 polyunsaturated fatty acids, and nucleotides could boost liver function recovery, immune response, and resistance to infection after hepatic resection. We conducted a placebo-controlled, randomized, double-blind study to assess the effect of a perioperative nutritional supplementation with Oral Impact(r) in patients undergoing hepatic surgery for liver cancer. Treatment was given three times daily for 7 days before and 3 days after surgery. Primary outcome was factor V, 3 days after surgery. Thirty-five patients (placebo: 17; Oral Impact: 18) were included. Five patients (placebo: three; Oral Impact: two) were not operated and five (placebo: two; Oral Impact: three) did not undergo hepatic resection. Factor V (mean +/- SD) was 70 +/- 27% and 79 +/- 25% (P = 0.409) 3 days after surgery and 90 +/- 30% and 106 +/- 16% (P = 0.066) 5 days after surgery, in placebo and Oral Impact groups, respectively. There were no significant differences between groups on other outcomes assessing liver function recovery (bile production, gamma-glutamyl transferase, alpha-fetoprotein), immune response (CD3, CD4, CD8 cells, CD4/CD8 ratio, natural killer cells, B lymphocytes), number of infections, and tolerance. A 10-day perioperative nutritional supplementation with Oral Impact does not improve hepatic function, immune response, and resistance to infection in patients undergoing hepatic surgery for liver cancer. PMID- 27007027 TI - Impact of the A2V Mutation on the Heterozygous and Homozygous Abeta1-40 Dimer Structures from Atomistic Simulations. AB - The A2V mutation was reported to protect from Alzheimer's disease in its heterozygous form and cause an early Alzheimer's disease type dementia in its homozygous form. Experiments showed that the aggregation rate follows the order A2V > WT (wild-type) > A2V-WT. To understand the impact of this mutation, we carried out replica exchange molecular dynamics simulations of Abeta1-40 WT-A2V and A2V-A2V dimers and compared to the WT dimer. Our atomistic simulations reveal that the mean secondary structure remains constant, but there are substantial differences in the intramolecular and intermolecular conformations upon single and double A2V mutation. Upon single mutation, the intrinsic disorder is reduced, the intermolecular potential energies are reduced, the population of intramolecular three-stranded beta-sheets is increased, and the number of all alpha dimer topologies is decreased. Taken together, these results offer an explanation for the reduced aggregation rate of the Abeta1-40 A2V-WT peptides and the protective effect of A2V in heterozygotes. PMID- 27007028 TI - Evaluation of an unstructured afterschool physical activity programme for disadvantaged youth. AB - The purpose of the study was to conduct an evaluation of an unstructured afterschool physical activity (PA) programme (Keep it Moving!; KIM) in an ethnically diverse and low socio-economic status (SES) school district. PA of students in 3rd-5th grades (N = 205) at four elementary schools were assessed during spring 2012. An ActiGraph accelerometer was utilised to examine objectively measured time and steps in differing intensity levels. Standard data reduction procedures were used to process collected data and characterise PA. Students averaged approximately 54 min of accelerometer wear-time during the KIM programme, 10.4 +/- 6.1 min (19.2%) of which were spent in sedentary behaviour, 28.2 +/- 8.3 min (52.1%) in light PA and 15.6 +/- 6.6 min (28.7%) in moderate-to vigorous intensity PA. Within the cadence band of 1-19 steps/min participants accumulated the highest time-derived PA (16.4 +/- 6.3 min). In total, children averaged 1811.9 +/- 527.5 steps during the entire KIM programme. Results from the programme indicated that elementary-aged students received additional PA through the KIM programme. The mean value of accumulated steps during the afterschool PA programme represented 12-16.5% of the minimum steps/day target (depending upon gender) identified for elementary-aged school children. These data represent unique findings from a high-need population that may be helpful for researchers and practitioners alike. PMID- 27007030 TI - The effect of phenol concentration on the treatment of pilonidal sinus disease: Early results of a prospective randomized study. AB - OBJECTIVE: Our hypothesis was that a low concentration (30%) of phenol would be more effective than a high concentration (80%) in the treatment of pilonidal disease. The purpose of our study was to compare the effects of high and low doses of liquid phenol in the treatment of pilonidal disease. SUMMARY OF BACKGROUND DATA: In the treatment of the pilonidal disease, the phenolization technique and concentration of the phenol solution is not well defined. METHODS: Consecutive patients being treated for pilonidal disease with high and low concentrations of phenol were included in this randomized prospective study. The demographic data, pilonidal disease characteristics, and results of phenol application were examined. RESULTS: Of 101 subjects, 52 were treated with 80% phenol while 49 were treated with 30% phenol. The mean observation period was approximately 1 year. The total recovery rate was higher among the 80% phenol group (P: 0.046). The recovery period, the period of leave from work, and complication rates were similar in both groups (p: 0.414, 0.328, 0.256). Also, in the Likert-type survey administered by validated methods, there was no difference in the degree of satisfaction (P: 0.494). CONCLUSION: The low concentrations of phenol did not achieve faster recovery, faster return to work, or less complications in the treatment of pilonidal disease. An 80% concentration of phenol should be used for a higher rate of recovery. PMID- 27007029 TI - Sociodemographic Characteristics and Health Status of Lifetime Abstainers, Ex Drinkers, Bingers, and Nonbingers Among Baby Boomers and Older Adults. AB - BACKGROUND: Health risks associated with abstention from alcohol drinking in previous studies may have been exaggerated because the pool of abstainers in many studies included both lifetime abstainers and ex-drinkers, including sick quitters. OBJECTIVES: This study compared sociodemographic and health statuses among lifetime abstainers, exdrinkers, bingers, and nonbingers in the 50-64 age group (baby boomers) and the 65+ age group. METHODS: Data are from the 2008 to 2012 National Survey on Drug Use and Health (N = 18,443 for the 50-64 age group and N = 11,191 for the 65+ age group). Descriptive statistics and multinomial and binary logistic regression analyses were used to examine the study questions. RESULTS: 10% of the 50-64 age group and 20% of the 65+ age group reported lifetime abstention, and 21% and 28% of each group, respectively, reported being ex-drinkers (i.e., last used alcohol more than 12 months ago). In both age groups, lifetime abstainers, exdrinkers, and bingers had lower socioeconomic status than nonbingers. In the 50-64 age group, lifetime abstainers did not differ from or were less likely than nonbingers to have vascular and hepatic/gastrointestinal (HGI) disorders, but exdrinkers were more likely to have these diseases, and both lifetime abstainers and exdrinkers were more likely to have diabetes. In the 65+ age group, lifetime abstainers did not differ from nonbingers on high blood pressure, heart disease, and HGI, but both they and the exdrinkers were more likely to have stroke and diabetes. CONCLUSIONS/IMPORTANCE: Diabetes screening/monitoring and stroke prevention/care are recommended for both age groups of abstainers and exdrinkers. PMID- 27007032 TI - Assembling the protist puzzle. PMID- 27007031 TI - Understanding and Designing the Gold-Bio Interface: Insights from Simulations. AB - Gold nanoparticles (AuNPs) are an integral part of many exciting and novel biomedical applications, sparking the urgent need for a thorough understanding of the physicochemical interactions occurring between these inorganic materials, their functional layers, and the biological species they interact with. Computational approaches are instrumental in providing the necessary molecular insight into the structural and dynamic behavior of the Au-bio interface with spatial and temporal resolutions not yet achievable in the laboratory, and are able to facilitate a rational approach to AuNP design for specific applications. A perspective of the current successes and challenges associated with the multiscale computational treatment of Au-bio interfacial systems, from electronic structure calculations to force field methods, is provided to illustrate the links between different approaches and their relationship to experiment and applications. PMID- 27007033 TI - Discrepancies between net particulate carbon production and (13) C-labelled bicarbonate uptake by Alexandrium catenella (Dinophyceae): grazing controls the balance between autotrophic and non autotrophic carbon acquisition(1). AB - Inorganic carbon uptake by Alexandrium catenella estimated from incorporation of (13) C labelled bicarbonate (an estimate of carbon gain by autotrophy) was compared to increases in particulate carbon (PC) that integrate all processes leading to carbon gain by cells (autotrophy, heterotrophy, mixotrophy). During blooms of A. catenella in the field, the (13) C tracer technique could account for only 47% (range 29%-59%) of the increase in PC in conventional 24 h incubations. From dilution experiments, the ratio of PC increases to bicarbonate uptake was related significantly and positively to the grazing rate, indicating that dissolved organic carbon contributes to growth as a direct function of grazing activity. In addition, as grazing rate increases, the contribution of dissolved inorganic carbon uptake to carbon-based growth decreases in a linear way (from 56% to 33% of total C acquisition) and the contribution of non autotrophic processes increases (from 54% to 67%). Thus, grazing appears to closely control the balance between autotrophic and non autotrophic processes leading to carbon acquisition by natural populations of A. catenella. PMID- 27007034 TI - Isolation of clonal axenic strains of the symbiotic dinoflagellate Symbiodinium and their growth and host specificity(1). AB - The cnidarian-dinoflagellate mutualism is integral to the survival of the coral reef ecosystem. Despite the enormous ecological and economic importance of corals, their cellular and molecular biology and the ways in which they respond to environmental change are still poorly understood. We have been developing a proxy system for examining the coral mutualism in which the dinoflagellate symbiont Symbiodinium is introduced into a clonal population of the host Aiptasia, a small sea anemone closely related to corals. To further develop the tools for this system, we generated five clonal, axenic strains of Symbiodinium and verified the lack of contaminants by growth on rich medium, microscopic examination, and PCR analysis. These strains were assigned to clades A (two strains), B, E, and F based on their chloroplast 23S rDNA sequences. Growth studies in liquid cultures showed that the clade B strain and one of the clade A strains were able to grow photoautotrophically (in light with no fixed carbon), mixotrophically (in light with fixed carbon), or heterotrophically (in dark with fixed carbon). The clade E strain, thought to be free-living, was able to grow photoautotrophically but not heterotrophically. Infection of an aposymbiotic Aiptasia host with the axenic strains showed consistent patterns of specificity, with only the clade B and one of the clade A strains able to successfully establish symbiosis. Overall, the Aiptasia-Symbiodinium association represents an important model system for dissecting aspects of the physiology and cellular and molecular biology of cnidarian-dinoflagellate mutualism and exploring issues that bear directly on coral bleaching. PMID- 27007035 TI - Auxin and cytokinin relationships in 24 microalgal strains(1). AB - Endogenous auxins and cytokinins were quantitated in 24 axenic microalgal strains from the Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Charophyceae. These strains were in an exponential growth phase, being harvested on day 4. Acutodesmus acuminatus Mosonmagyarovar Algal Culture Collection-41 (MACC) produced the highest biomass and Chlorococcum ellipsoideum MACC-712 the lowest biomass. The auxins, indole-3-acetic acid (IAA) and indole-3-acetamide (IAM) were present in all microalgal strains. No other auxin conjugates were detected. IAA and IAM concentrations varied greatly, ranging from 0.50 to 71.49 nmol IAA . g( 1) DW and 0.18 to 99.83 nmol IAM . g(-1) DW, respectively. In 19 strains, IAA occurred in higher concentrations than IAM. Nineteen cytokinins were identified in the microalgal strains. Total cytokinin concentrations varied, ranging from 0.29 nmol . g(-1) DW in Klebsormidium flaccidum MACC-692 to 21.40 nmol . g(-1) DW in Stigeoclonium nanum MACC-790. The general trend was that cis-zeatin types were the predominant cytokinins; isopentenyladenine-type cytokinins were present in moderate concentrations, while low levels of trans-zeatin-type and very low levels of dihydrozeatin-type cytokinins were detected. Ribotides were generally the main cytokinin conjugate forms present with the cytokinin free bases and ribosides present in similar but moderate levels. The levels of O-glucosides were low. Only one N-glucoside was detected, being present in nine strains in very low concentrations. In 15 strains, the auxin content was 2- to 4-fold higher than the cytokinin content. PMID- 27007036 TI - Temporal dynamics of inducible anti-herbivory defenses in the brown seaweed Ascophyllum nodosum (Phaeophyceae)(1). AB - Anti-herbivory defenses support persistence of seaweeds. Little is known, however, about temporal dynamics in the induction of grazer-deterrent seaweed traits. In two induction experiments, consumption rates of the periwinkle Littorina obtusata (L.) on the brown seaweed Ascophyllum nodosum (L.) Le Jolis were measured in 3-d intervals. Changes in palatability of directly grazed A. nodosum were tested every 3 d with feeding assays using fresh and reconstituted seaweed pieces. Likewise, assays with fresh A. nodosum assessed changes in seaweed palatability in response to water-borne cues from nearby grazed conspecifics. Consumption rates of L. obtusata varied significantly during the 27 d induction phase of each experiment. Direct grazing by L. obtusata lowered palatability of fresh and reconstituted A. nodosum pieces to conspecific grazers after 15 d as well as after 6 and 12 d, respectively. After 12, 18, and 24 d, fresh A. nodosum located downstream of L. obtusata-grazed conspecifics was significantly less palatable than A. nodosum located downstream of ungrazed conspecifics. Changes in L. obtusata consumption rates and A. nodosum palatability during both induction experiments suggest temporal variation of grazer-deterrent responses, which may complicate experimental detection of inducible anti-herbivory defenses. PMID- 27007037 TI - Effects of pCO2 and iron on the elemental composition and cell geometry of the marine diatom Pseudo-nitzschia pseudodelicatissima (Bacillariophyceae)(1). AB - Partial pressure of CO2 (pCO2 ) and iron availability in seawater show corresponding changes due to biological and anthropogenic activities. The simultaneous change in these factors precludes an understanding of their independent effects on the ecophysiology of phytoplankton. In addition, there is a lack of data regarding the interactive effects of these factors on phytoplankton cellular stoichiometry, which is a key driving factor for the biogeochemical cycling of oceanic nutrients. Here, we investigated the effects of pCO2 and iron availability on the elemental composition (C, N, P, and Si) of the diatom Pseudo-nitzschia pseudodelicatissima (Hasle) Hasle by dilute batch cultures under 4 pCO2 (~200, ~380, ~600, and ~800 MUatm) and five dissolved inorganic iron (Fe'; ~5, ~10, ~20, ~50, and ~100 pmol . L(-1) ) conditions. Our experimental procedure successfully overcame the problems associated with simultaneous changes in pCO2 and Fe' by independently manipulating carbonate chemistry and iron speciation, which allowed us to evaluate the individual effects of pCO2 and iron availability. We found that the C:N ratio decreased significantly only with an increase in Fe', whereas the C:P ratio increased significantly only with an increase in pCO2 . Both Si:C and Si:N ratios decreased with increasing pCO2 and Fe'. Our results indicate that changes in pCO2 and iron availability could influence the biogeochemical cycling of nutrients in future oceans with high- CO2 levels, and, similarly, during the time course of phytoplankton blooms. Moreover, pCO2 and iron availability may also have affected oceanic nutrient biogeochemistry in the past, as these conditions have changed markedly over the Earth's history. PMID- 27007038 TI - Algal turf scrubber (ATS) floways on the Great Wicomico River, Chesapeake Bay: productivity, algal community structure, substrate and chemistry(1). AB - Two Algal Turf Scrubber (ATS) units were deployed on the Great Wicomico River (GWR) for 22 months to examine the role of substrate in increasing algal productivity and nutrient removal. The yearly mean productivity of flat ATS screens was 15.4 g . m(-2) . d(-1) . This was elevated to 39.6 g . m(-2) . d( 1) with a three-dimensional (3-D) screen, and to 47.7 g . m(-2) . d(-1) by avoiding high summer harvest temperatures. These methods enhanced nutrient removal (N, P) in algal biomass by 3.5 times. Eighty-six algal taxa (Ochrophyta [diatoms], Chlorophyta [green algae], and Cyan-obacteria [blue-green algae]) self seeded from the GWR and demonstrated yearly cycling. Silica (SiO2 ) content of the algal biomass ranged from 30% to 50% of total biomass; phosphorus, nitrogen, and carbon content of the total algal biomass ranged from 0.15% to 0.21%, 2.13% to 2.89%, and 20.0% to 25.7%, respectively. Carbohydrate content (at 10%-25% of AFDM) was dominated by glucose. Lipids (fatty acid methyl ester; FAMEs) ranged widely from 0.5% to 9% AFDM, with Omega-3 fatty acids a consistent component. Mathematical modeling of algal produ-ctivity as a function of temperature, light, and substrate showed a proportionality of 4:3:3, resp-ectively. Under landscape ATS operation, substrate manipulation provides a considerable opportunity to increase ATS productivity, water quality amelioration, and biomass coproduction for fertilizers, fermentation energy, and omega-3 products. Based on the 3-D prod uctivity and algal chemical composition demonstrated, ATS systems used for nonpoint source water treat-ment can produce ethanol (butanol) at 5.8* per unit area of corn, and biodiesel at 12.0* per unit area of soy beans (agricultural production US). PMID- 27007039 TI - Measuring carbon and N2 fixation in field populations of colonial and free-living unicellular cyanobacteria using nanometer-scale secondary ion mass spectrometry(1). AB - Unicellular cyanobacteria are now recognized as important to the marine N and C cycles in open ocean gyres, yet there are few direct in situ measurements of their activities. Using a high-resolution nanometer scale secondary ion mass spectrometer (nanoSIMS), single cell N2 and C fixation rates were estimated for unicellular cyanobacteria resembling N2 fixer Crocosphaera watsonii. Crocosphaera watsonii-like cells were observed in the subtropical North Pacific gyre (22 degrees 45' N, 158 degrees 0' W) as 2 different phenotypes: colonial and free living. Colonies containing 3-242 cells per colony were observed and cell density in colonies increased with incubation time. Estimated C fixation rates were similarly high in both phenotypes and unexpectedly for unicellular cyanobacteria 85% of the colonial cells incubated during midday were also enriched in (15) N above natural abundance. Highest (15) N enrichment and N2 fixation rates were found in cells incubated overnight where up to 64% of the total daily fixed N in the upper surface waters was attributed to both phenotypes. The colonial cells retained newly fixed C in a sulfur-rich matrix surrounding the cells and often cells of both phenotypes possessed areas (<1 nm) of enriched (15) N and (13) C resembling storage granules. The nanoSIMS imaging of the colonial cells also showed evidence for a division of N2 and C fixation activity across the colony where few individual cells (<34%) in a given colony were enriched in both (15) N and (13) C above the colony average. Our results provide new insights into the ecophysiology of unicellular cyanobacteria. PMID- 27007040 TI - Genetic similarity analysis within Pyropia yezoensis blades developed from both conchospores and blade archeospores using AFLP(1). AB - Pyropia yezoensis (Ueda) M. S. Hwang et H. G. Choi (previously called Porphyra yezoensis) is an economically important alga. The blades generated from conchospores are genetic chimeras, which are not suitable for genetic similarity analysis. In this study, two types of blades from a single filament of P. yezoensis sporophyte filament were obtained. One type, ConB, consisted of 40 blades that had germinated from conchospores. The other type, ArcB, consisted of 88 blades that had germinated from archeospores released from ConB. Both of them were analyzed by amplified fragment length polymorphism. The low genetic similarity levels for both conchospore-germinated and archeospore-germinated blades demonstrated that the conchcelis we used was cross-fertilized. Furthermore, a higher polymorphic loci ratio (98.6%) was detected in ArcB than in ConB (80.7%), and the average genetic similarity of ArcB (average 0.61) was lower than that of ConB (average 0.71). These differences indicated that genetic analysis using ArcB gives more accurate results. PMID- 27007041 TI - Carbon allocation under light and nitrogen resource gradients in two model marine phytoplankton(1). AB - Marine phytoplankton have conserved elemental stoichiometry, but there can be significant deviations from this Redfield ratio. Moreover, phytoplankton allocate reduced carbon (C) to different biochemical pools based on nutritional status and light availability, adding complexity to this relationship. This allocation influences physiology, ecology, and biogeochemistry. Here, we present results on the physiological and biochemical properties of two evolutionarily distinct model marine phytoplankton, a diatom (cf. Staurosira sp. Ehrenberg) and a chlorophyte (Chlorella sp. M. Beijerinck) grown under light and nitrogen resource gradients to characterize how carbon is allocated under different energy and substrate conditions. We found that nitrogen (N)-replete growth rate increased monotonically with light until it reached a threshold intensity (~200 MUmol photons . m(-2) . s(-1) ). For Chlorella sp., the nitrogen quota (pg . MUm(-3) ) was greatest below this threshold, beyond which it was reduced by the effect of N stress, while for Staurosira sp. there was no trend. Both species maintained constant maximum quantum yield of photosynthesis (mol C . mol photons(-1) ) over the range of light and N-gradients studied (although each species used different photophysiological strategies). In both species, C:chl a (g . g(-1) ) increased as a function of light and N-stress, while C:N (mol . mol(-1) ) and relative neutral lipid:C (rel. lipid . g(-1) ) were most strongly influenced by N-stress above the threshold light intensity. These results demonstrated that the interaction of substrate (N-availability) and energy gradients influenced C allocation, and that general patterns of biochemical responses may be conserved among phytoplankton; they provided a framework for predicting phytoplankton biochemical composition in ecological, biogeochemical, or biotechnological applications. PMID- 27007042 TI - Autecology and phylogeny of Coolia tropicalis and Coolia malayensis (Dinophyceae), with emphasis on taxonomy of C. tropicalis based on light microscopy, scanning electron microscopy and LSU rDNA(1). AB - Coolia is a widespread and ecologically important genus of benthic marine dinoflagellates found in tropical regions. Historically, there has been taxonomic confusion about the taxonomy and toxicity of this group. The goal of this study was to resolve morphological questions concerning Coolia tropicalis and determine the taxonomic identity of the Australian Coolia isolate which has been reported to produce cooliatoxins. To accomplish this, the morphology of tropical strains from Belize (the type locality of C. tropicalis), Malaysia, Indonesia, and Australia were examined and compared to published reports. The morphological analysis showed that C. tropicalis differs from the original description in that it has a slightly larger size (35-47 MUm long by 30-45 MUm wide versus 23-40 MUm long by 25-39 MUm wide), and the shape of fourth apical plate, and the length of Po plate (7.4-12 MUm versus 7 MUm). Based on both morphology and phylogenetic analysis using LSU D1- D3 rDNA sequences, the clones of C. tropicalis from Malaysia, Indonesia, and Belize were found to form a monophyletic clade within the genus. The strain producing cooliatoxin was found to be C. tropicalis, not Coolia monotis as originally assumed. To explore the factors influencing the growth of Coolia species, the growth rates of C. tropicalis and Coolia malayensis were determined at different temperatures and salinities. Both species tolerated a wide range of temperatures, but cannot survive at temperatures <20 degrees C or >35 degrees C. C. monotis, the dominant species reported in the literature, probably does not produce toxins. PMID- 27007043 TI - The role of dissolved organic matter (DOM) quality in the growth enhancement of Alexandrium fundyense (Dinophyceae) in laboratory culture(1). AB - Several algal species responsible for harmful algal blooms (HABs), such as Alexandrium fundyense, are mixotrophic under certain environmental conditions. The ability to switch between photosynthetic and heterotrophic modes of growth may play a role in the development of HABs in coastal regions. We examined the influence of humic dissolved organic matter (HDOM) derived from terrestrial (plant/soil) and microbial sources on the growth of A. fundyense. We found that a terrestrially derived HDOM, Suwannee River humic acid (SRHA), did enhance A. fundyense growth; however, a microbially derived HDOM, Pony Lake fulvic acid (PLFA) did not enhance growth. A. fundyense grows in association with bacteria in culture and we observed that bacterial cell densities were much lower in A. fundyense cultures than in bacteria-only cultures, consistent with bacterial grazing by A. fundyense in culture. In bacteria-only cultures with added algal exudates (EX), the addition of PLFA and SRHA resulted in a slight increase in bacterial cell density compared to cultures without HDOM added. Changes over time in the chemical quality of the HDOM in the A. fundyense cultures reflected contributions of microbially derived material with similar characteristics as the PLFA. Overall, these results suggest that the chemical differences between SRHA and PLFA are responsible for the greater effect of SRHA on A. fundyense growth, and that the differential effect is not a result of an effect on the growth of associated bacteria. PMID- 27007044 TI - Bispinodinium angelaceum gen. et sp. nov. (Dinophyceae), a new sand-dwelling dinoflagellate from the seafloor off Mageshima Island, Japan(1). AB - A new athecate dinoflagellate, Bispinodinium angelaceum N. Yamada et Horiguchi gen. et sp. nov., is described from a sand sample collected on the seafloor at a depth of 36 m off Mageshima Island, subtropical Japan. The dinoflagellate is dorsiventrally compressed and axi-symmetric along the sulcus. The morphology resembles that of the genus Amphidinium sensu lato by having a small epicone that is less than one third of the total cell length. However, it has a new type of apical groove, the path of which traces the outline of a magnifying glass. The circular component of this path forms a complete circle in the center of the epicone and the straight "handle" runs from the sulcus to the circular component. Inside the cell, a pair of elongated fibrous structure termed here the "spinoid apparatus" extends from just beneath the circular apical groove to a point near the nucleus. Each of two paired structures consists of at least 10 hyaline fibers and this is a novel structure found in dinoflagellates. Phylogenetic analyses based on the SSU and LSU RNA genes did not show any high bootstrap affinities with currently known athecate dinoflagellates. On the basis of its novel morphological features and molecular signal, we conclude that this dinoflagellate should be described as a new species belonging to a new genus. PMID- 27007045 TI - Polyadenylation of 18S rRNA in algae(1). AB - Polyadenylation is best known for occurring to mRNA of eukaryotes transcribed by RNA polymerase II to stabilize mRNA molecules and promote their translation. rRNAs transcribed by RNA polymerase I or III are typically believed not to be polyadenylated. However, there is increasing evidence that polyadenylation occurs to nucleus-encoded rRNAs as part of the RNA degradation pathway. To examine whether the same polyadenylation-assisted degradation pathway occurs in algae, we surveyed representative species of algae including diatoms, chlorophytes, dinoflagellates and pelagophytes using oligo (dT)-primed reversed transcription PCR (RT-PCR). In all the algal species examined, truncated 18S rRNA or its precursor molecules with homo- or hetero-polymeric poly(A) tails were detected. Mining existing algal expressed sequence tag (EST) data revealed polyadenylated truncated 18S rRNA in four additional phyla of algae. rRNA polyadenylation occurred at various internal positions along the 18S rRNA and its precursor sequences. Moreover, putative homologs of noncanonical poly(A) polymerase (ncPAP) Trf4p, which is responsible for polyadenylating nuclear-encoded RNA and targeting it for degradation, were detected from the genomes and transcriptomes of five phyla of algae. Our results suggest that polyadenylation-assisted RNA degradation mechanism widely exists in algae, particularly for the nucleus-encoded rRNA and its precursors. PMID- 27007046 TI - Potassium deficiency triggers the development of dormant cells (akinetes) in Aphanizomenon ovalisporum (Nostocales, Cyanoprokaryota)(1). AB - Akinetes are spore-like nonmotile cells that differentiate from vegetative cells of filamentous cyanobacteria from the order Nostocales. They play a key role in the survival and distribution of these species and contribute to their perennial blooms. Various environmental factors were reported to trigger the differentiation of akinetes including light intensity and quality, temperature, and nutrient deficiency. Here, we report that deprivation of potassium ion (K(+) ) triggers akinete development in the cyanobacterium Aphanizomenon ovalisporum. Akinetes formation is initiated 3 d-7 d after an induction by K(+) depletion, followed by 2-3 weeks of a maturation process. Akinete formation occurs within a restricted matrix of environmental conditions such as temperature, light intensity or photon flux. Phosphate is essential for akinete maturation and P limitation restricts the number of mature akinetes. DNA replication is essential for akinete maturation and akinete development is limited in the presence of Nalidixic acid. While our results unequivocally demonstrated the effect of K(+) deficiency on akinete formation in laboratory cultures of A. ovalisporum, this trigger did not cause Cylindrospermopsis raciborskii to produce akinetes. Anabaena crassa however, produced akinetes upon potassium deficiency, but the highest akinete concentration was achieved at conditions that supported vegetative growth. It is speculated that an unknown internal signal is associated with the cellular response to K(+) deficiency to induce the differentiation of a certain vegetative cell in a trichome into an akinete. A universal stress protein that functions as mediator in K(+) deficiency signal transduction cascade, may communicate between the lack of K(+) and akinete induction. PMID- 27007047 TI - Identity and phylogenetic placement of Spirogyra species (Zygnematophyceae, Charophyta) from California streams and elsewhere(1). AB - Diversity of the filamentous green algae in the genus Spirogyra (Zygnematophyceae) was investigated from more than 1,200 stream samples from California. We identified 12 species of Spirogyra not previously known for California (CA), including two species new to science, Spirogyra californica sp. nov. and Spirogyra juliana sp. nov. Environmental preferences of the Californian species are discussed in the light of their restricted distribution to stream habitats with contrasting nutrient levels. We also investigated the systematic relationships of Spirogyra species from several continents using the chloroplast encoded genes ribulose-1,5-bisphosphate carboxylase/hydrogenase large subunit (rbcL) and the beta subunit of the ATP synthase (atpB). Californian species were positioned in most major clades of Spirogyra. The phylogeny of Spirogyra and its taxonomic implications are discussed, such as the benefits of combining structural and molecular data for more accurate and consistent species identification. Considerable infraspecific genetic variation of globally distributed Spirogyra species was observed across continental scales. This finding suggests that structurally similar species from distant regions may be genetically dissimilar and that Spirogyra may contain a large number of cryptic species. Correlating the morphological and genetic variation within the genus will be a major challenge for future researchers. PMID- 27007048 TI - Simulating pH effects in an algal-growth hydrodynamics model(1). AB - Models and numerical simulations are relatively inexpensive tools that can be used to enhance economic competitiveness through operation and system optimization to minimize energy and resource consumption, while maximizing algal oil yield. This work uses modified versions of the U.S. Environmental Protection Agency's Environmental Fluid Dynamics Code (EFDC) in conjunction with the U.S. Army Corp of Engineers' water-quality code (CE-QUAL) to simulate flow hydrodynamics coupled to algal growth kinetics. The model allows the flexibility of manipulating a host of variables associated with algal growth such as temperature, light intensity, and nutrient availability. pH of the medium is a newly added operational parameter governing algal growth that affects algal photosynthesis, differential availability of inorganic forms of carbon, enzyme activity in algae cell walls, and oil production rates. A single-layer algal growth/hydrodynamic model without pH limitation was verified by comparing solution curves of algal biomass and phosphorus concentrations to an analytical solution. Media pH, now included in the model as a growth-limiting factor, can be entered as a measured value or calculated based on CO2 concentrations. Upon adding the ability to limit growth due to pH, physically reasonable results have been obtained from the model both with and without pH limitation. When the model was used to simulate algal growth from a pond experiment in the greenhouse, a least-squares fitting technique yielded a maximum algal production (subsequently modulated by limitation factors) of 1.05 d(-1) . Overall, the measured and simulated biomass concentrations in the greenhouse pond were in close agreement. PMID- 27007049 TI - A redescription of morphologically similar species from the genus Euglena: E. laciniata, E. sanguinea, E. sociabilis, and E. splendens(1). AB - Euglena sanguinea (Ehrenberg 1831) was one of the first green euglenoid species described in the literature. At first, the species aroused the interest of researchers mainly due to the blood-red color of its cells, which, as it later turned out, is not a constant feature. Complicated chloroplast morphology, labeled by Pringsheim as the "peculiar chromatophore system", made the correct identification of the species difficult, which is the reason why, throughout the 20th century, new species resembling E. sanguinea were continually being named due to a lack of suitable diagnostic features to distinguish E. sanguinea. Interest in E. sanguinea has returned in recent years, following findings that the species can produce ichthyotoxins. This was followed by the need to classify E. sanguinea correctly, which was achieved through the verification of morphological and molecular data for all species similar to E. sanguinea. As the result of the analysis, the number of species sharing some morphological similarities with E. sanguinea could be reduced from 12, as described in the literature, to four, with established epitypes and updated diagnostic descriptions. The most important diagnostic features included: the presence of mucocysts (i.e., whether they were visible before and/or after staining), the number of chloroplasts, the size of the double-sheathed pyrenoids, and the presence of the large paramylon grain in the vicinity of the stigma. Moreover, sequence analysis revealed the presence of unusually long SSU rDNA sequences in E. sanguinea. Previously, SSU rDNA sequences of such length were known to be present in primary osmotrophic euglenoids. PMID- 27007050 TI - T cells conditioned with MDSC show an increased anti-tumor activity after adoptive T cell based immunotherapy. AB - The success of adoptive T cell-based immunotherapy (ACT) in cancer is limited in part by the accumulation of myeloid-derived suppressor cells (MDSC), which block several T cell functions, including T cell proliferation and the expression of various cytotoxic mediators. Paradoxically, the inhibition of CD8+ T cell differentiation into cytotoxic populations increased their efficacy after ACT into tumor-bearing hosts. Therefore, we aimed to test the impact of conditioning CD8+ T cells with MDSC on their differentiation potential and ACT efficacy. Our results indicate that MDSC impaired the progression of CD8+ T cells into effector populations, without altering their activation status, production of IL-2, or signaling through the T cell receptor. In addition, culture of CD8+ T cells with MDSC resulted in an increased ACT anti-tumor efficacy, which correlated with a higher frequency of the transferred T cells and elevated IFNgamma production. Interestingly, activated CD62L+ CD8+ T cells were responsible for the enhanced anti-tumor activity showed by MDSC-exposed T cells. Additional results showed a decreased protein synthesis rate and lower activity of the mammalian/mechanistic target of rapamycin (mTOR) in T cells conditioned with MDSC. Silencing of the negative mTOR regulator tuberous sclerosis complex-2 in T cells co-cultured with MDSC restored mTOR activity, but resulted in T cell apoptosis. These results indicate that conditioning of T cells with MDSC induces stress survival pathways mediated by a blunted mTOR signaling, which regulated T cell differentiation and ACT efficacy. Continuation of this research will enable the development of better strategies to increase ACT responses in cancer. PMID- 27007051 TI - Artificial antigen-presenting cells expressing AFP(158-166) peptide and interleukin-15 activate AFP-specific cytotoxic T lymphocytes. AB - Professional antigen-presenting cells (APCs) are potent generators of tumor antigen-specific cytotoxic T lymphocytes (CTLs) for adoptive immunotherapy; however, generation of APCs is cumbersome, expensive, and subject to the tumor microenvironment. Artificial APCs (aAPCs) have been developed as a cost-effective alternative to APCs. We developed a cellular aAPC that efficiently generated alpha-fetoprotein (AFP)-specific CTLs. We genetically modified the human B cell lymphoma cell line BJAB with a lentiviral vector to establish an aAPC called BA15. The expression of AFP(158-166)-HLA-A*02:01 complex, CD80, CD86, and interleukin (IL)-15 in BA15 cells was assessed. The efficiency of BA15 at generating AFP-specific CTLs and the specific cytotoxicity of CTLs against AFP+ cells were also determined. BA15 cells expressed high levels of AFP(158-166) peptide, HLA-A2, CD80, CD86, and IL-15. BA15 cells also exhibited higher efficiency in generating AFP-specific CTLs than did dendritic cells. These CTLs had greater cytotoxicity against AFP+ hepatocellular carcinoma cells than did CTLs obtained from dendritic cells in vitro and in vivo. Our novel aAPC system could provide a robust platform for the generation of functional AFP-specific CTLs for adoptive immunotherapy of hepatocellular carcinoma. PMID- 27007052 TI - Differential regulation of the c-Myc/Lin28 axis discriminates subclasses of rearranged MLL leukemia. AB - MLL rearrangements occur in myeloid and lymphoid leukemias and are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute myeloid leukemia (AML) in mice using various MLL fusion proteins (MLL-FPs) and observed significantly different survival outcomes. To better understand the differences between these leukemias, we examined the genome wide expression profiles of leukemic cells transformed with different MLL-FPs. RNA-sequencing and pathway analysis identified the c-Myc transcriptional program as one of the top distinguishing features. c-Myc protein levels were highly correlative with AML disease latency in mice. Functionally, overexpression of c Myc resulted in a more aggressive proliferation rate in MLL-FP cell lines. While all MLL-FP transformed cells displayed sensitivity to BET inhibitors, high c-Myc expressing cells showed greater resistance to Brd4 inhibition. The Myc target Lin28B was also differentially expressed in MLL-FP cell lines in agreement with c Myc expression. Examination of Lin28B miRNAs targets revealed that let-7g was significantly increased in leukemic cells associated with the longest disease latency and forced let-7g expression induced differentiation of leukemic blasts. Thus, differential regulation of the c-Myc/Lin28/let-7g program by different MLL FPs is functionally related to disease latency and BET inhibitor resistance in MLL leukemias. PMID- 27007054 TI - Interplay between myeloid-derived suppressor cells (MDSCs) and Th17 cells: foe or friend? AB - Myeloid-derived suppressor cells (MDSCs) and Th17 cells were first discovered in the fields of cancer and autoimmunity, respectively. In recent years, their activities have been explored in other biological and pathological conditions, such as infective diseases and solid organ transplantation. However, the interplay between MDSCs and Th17 cells and the mechanism of their interaction remain obscure. This review summarized and analyzed the relationship between MDSCs and Th17 cells, both of which participate in tumor, autoimmune disease, infection and other conditions. In tumors, the increase in MDSCs at the tumor site is usually accompanied by the accumulation of Th17 cells. However, their relationship is inconsistent in different tumors. In arthritic mice or rheumatoid arthritis (RA) patients, an increase in MDSCs, which could ameliorate disease symptoms, causes decreased IL-17A gene expression and Th17 cells accumulation. Furthermore, we concluded that the interaction between MDSCs and Th17 cells is mainly mediated by cytokines. However, the mechanisms require further investigation. Determining the details of their interplay will provide a better understanding of immune networks and could lead to the development of immunotherapeutic strategies in the future. PMID- 27007053 TI - Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies. AB - Fibroblast growth factor (FGF) signaling is essential for normal and cancer biology. Mammalian FGF family members participate in multiple signaling pathways by binding to heparan sulfate and FGF receptors (FGFR) with varying affinities. FGF2 is the prototype member of the FGF family and interacts with its receptor to mediate receptor dimerization, phosphorylation, and activation of signaling pathways, such as Ras-MAPK and PI3K pathways. Excessive mitogenic signaling through the FGF/FGFR axis may induce carcinogenic effects by promoting cancer progression and increasing the angiogenic potential, which can lead to metastatic tumor phenotypes. Dysregulated FGF/FGFR signaling is associated with aggressive cancer phenotypes, enhanced chemotherapy resistance and poor clinical outcomes. In vitro experimental settings have indicated that extracellular FGF2 affects proliferation, drug sensitivity, and apoptosis of cancer cells. Therapeutically targeting FGF2 and FGFR has been extensively assessed in multiple preclinical studies and numerous drugs and treatment options have been tested in clinical trials. Diagnostic assays are used to quantify FGF2, FGFRs, and downstream signaling molecules to better select a target patient population for higher efficacy of cancer therapies. This review focuses on the prognostic significance of FGF2 in cancer with emphasis on therapeutic intervention strategies for solid and hematological malignancies. PMID- 27007057 TI - The effect of low-volatile organic compounds, water-based paint on aggravation of allergic disease in schoolchildren. AB - Whether indoor painting aggravates preexisting allergic diseases remains unclear. We aimed to evaluate the impact of new classroom painting on aggravation of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) in children. Studied school was previously painted with conventional water-based paint 20 years ago and had natural ventilation system. We identified a total of 172 children aged 10 12 years with allergic diseases in 17 classrooms, which were allocated to newly painted rooms with low-volatile organic compounds (VOC), water-based paint, or existing rooms. After painting, there was no intervention or internal airflow to influence indoor air environment in both classrooms. We prospectively assessed the symptom severity and serious events of allergic diseases between both classrooms at baseline and after one and eight weeks after painting. At one and eight weeks, there were no significant changes in the Childhood Asthma Control Test scores, the fractional nitric oxide levels, lung function in asthmatic children in either classroom. There were also no significant changes in the severity score of AR or AD, or serious events in all allergic diseases. These findings suggest classroom painting with this new paint at the levels encountered in this study might not be a major aggravating factor for school-aged children with allergic diseases. PMID- 27007058 TI - Adding Four Extra K-Regions to Hexa-peri-hexabenzocoronene. AB - A multistep synthesis of hexa-peri-hexabenzocoronene (HBC) with four additional K regions was developed through a precursor based on two benzotetraphene units bridged with p-phenylene, featuring preinstalled zigzag moieties. Characterization by laser desorption/ionization time-of-flight mass spectrometry, Raman and IR spectroscopy, and scanning tunneling microscopy unambiguously validated the successful formation of this novel zigzag edge-rich HBC derivative. STM imaging of its monolayers revealed large-area, defect-free adlayers. The optical properties of the modified HBC were investigated by UV/visible absorption spectroscopy. PMID- 27007056 TI - Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment. AB - Osteosarcoma is the most common primary bone tumor in children and adolescents. Although combined therapy including surgery and multi-agent chemotherapy have resulted in great improvements in the overall survival of patients, chemoresistance remains an obstacle for the treatment of osteosarcoma. Molecular targets or effective agents that are actively involved in cell death including apoptosis, autophagy and necroptosis have been studied. We summarized how these agents (novel compounds, miRNAs, or proteins) regulate apoptotic, autophagic and necroptotic pathways; and discussed the current knowledge on the role of these new agents in chemotherapy resistance in osteosarcoma. PMID- 27007055 TI - Addressing the elephant in the room, therapeutic resistance in non-small cell lung cancer, with epigenetic therapies. AB - Like Chinese boxes nesting inside each other, the classification of non-small cell lung cancer (NSCLC) is subdivided into smaller and smaller subtypes on the basis of histological and molecular attributes. The latter characterizes NSCLC by its molecular alterations and the identification of inhibitors that target these cancer-specific "driver" mutations. Despite the initial promise of precision guided therapies to inhibit a finer and finer array of molecular subcategories, despite even the curative potential of immunotherapeutic checkpoint blockade, in particular, casualties still abound and true clinical success stories are few and far between; the ever-present, if sometimes unmentioned, "elephant in the room", is the acquisition of resistance, which, sooner or later, rears its ugly head to undermine treatment success and shorten survival. Emerging data suggests that epigenetic therapies are able to reprogram the aberrant tumor-associated epigenome and 'tame the beast of resistance', thereby prolonging survival. This article reviews the role of epigenetic dysregulation in NSCLC, explores PFS2 as a possible surrogate endpoint, briefly mentions possible biomarkers and highlights combinatorial treatment epigenetic strategies to "prime" tumors and reverse resistance. PMID- 27007059 TI - Minimizing Postsampling Degradation of Peptides by a Thermal Benchtop Tissue Stabilization Method. AB - Enzymatic degradation is a major concern in peptide analysis. Postmortem metabolism in biological samples entails considerable risk for measurements misrepresentative of true in vivo concentrations. It is therefore vital to find reliable, reproducible, and easy-to-use procedures to inhibit enzymatic activity in fresh tissues before subjecting them to qualitative and quantitative analyses. The aim of this study was to test a benchtop thermal stabilization method to optimize measurement of endogenous opioids in brain tissue. Endogenous opioid peptides are generated from precursor proteins through multiple enzymatic steps that include conversion of one bioactive peptide to another, often with a different function. Ex vivo metabolism may, therefore, lead to erroneous functional interpretations. The efficacy of heat stabilization was systematically evaluated in a number of postmortem handling procedures. Dynorphin B (DYNB), Leu enkephalin-Arg(6) (LARG), and Met-enkephalin-Arg(6)-Phe(7) (MEAP) were measured by radioimmunoassay in rat hypothalamus, striatum (STR), and cingulate cortex (CCX). Also, simplified extraction protocols for stabilized tissue were tested. Stabilization affected all peptide levels to varying degrees compared to those prepared by standard dissection and tissue handling procedures. Stabilization increased DYNB in hypothalamus, but not STR or CCX, whereas LARG generally decreased. MEAP increased in hypothalamus after all stabilization procedures, whereas for STR and CCX, the effect was dependent on the time point for stabilization. The efficacy of stabilization allowed samples to be left for 2 hours in room temperature (20 degrees C) without changes in peptide levels. This study shows that conductive heat transfer is an easy-to-use and efficient procedure for the preservation of the molecular composition in biological samples. Region- and peptide-specific critical steps were identified and stabilization enabled the optimization of tissue handling and opioid peptide analysis. The result is improved diagnostic and research value of the samples with great benefits for basic research and clinical work. PMID- 27007060 TI - Local electric fields and molecular properties in heterogeneous environments through polarizable embedding. AB - In spectroscopies, the local field experienced by a molecule embedded in an environment will be different from the externally applied electromagnetic field, and this difference may significantly alter the response and transition properties of the molecule. The polarizable embedding (PE) model has previously been developed to model the local field contribution stemming from the direct molecule-environment coupling of the electromagnetic response properties of molecules in solution as well as in heterogeneous environments, such as proteins. Here we present an extension of this approach to address the additional effective external field effect, i.e., the manifestations of the environment polarization induced by the external field, which allows for the calculation of properties defined in terms of the external field. Within a response framework, we report calculations of the one- and two-photon absorption (1PA and 2PA, respectively) properties of PRODAN-methanol clusters as well as the fluorescent protein DsRed. Our results demonstrate the necessity of accounting for both the dynamical reaction field and effective external field contributions to the local field in order to reproduce full quantum chemical reference calculations. For the lowest pi->pi* transition in DsRed, inclusion of effective external field effects gives rise to a 1.9- and 3.5-fold reduction in the 1PA and 2PA cross-sections, respectively. The effective external field is, however, strongly influenced by the heterogeneity of the protein matrix, and the resulting effect can lead to either screening or enhancement depending on the nature of the transition under consideration. PMID- 27007061 TI - Polypod-Shaped DNAs: Small-Angle X-ray Scattering and Immunostimulatory Activity. AB - We explored in detail the relationship between the structure in aqueous solution and immunostimulatory activity of polypod-shaped DNAs, called polypodnas. The polypodnas were constructed using 3-6 oligodeoxynucleotides (ODNs) to obtain tri , tetra-, penta-, and hexapodna, each of which had 3, 4, 5, and 6 arms made of double-stranded DNA, respectively. A highly potent immunostimulatory CpG sequence was included into each of the polypodnas. Synchrotron X-ray scattering analysis showed that the double-stranded DNA arms of all of the polypodnas adopted a B form DNA conformation. The analysis also suggested that some nucleotides in the central parts of pentapodna and hexapodna did not form base pairs, whereas those of tripodna and tetrapodna all formed base pairs. This difference would occur because of an increase in steric hindrance and electrical repulsion with increasing number of arms. The pentapodna and hexapodna induced a large amount of tumor necrosis factor alpha-release from macrophage-like cells compared with the tripodna and tetrapodna, suggesting that the partly loosened DNA in polypodna with many arms is advantageous for exposing the immunostimulatory sequences of the polypodna. PMID- 27007062 TI - N-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial. AB - IMPORTANCE: Excoriation (skin-picking) disorder (SPD) is a disabling, underrecognized condition in which individuals repeatedly pick at their skin, leading to noticeable tissue damage. To date, there has been no clearly effective pharmacologic or psychological treatment for SPD. OBJECTIVE: To determine whether N-acetylcysteine, an amino acid that appears to restore extracellular glutamate concentration in the nucleus accumbens, will be more effective than placebo in reducing compulsive picking behavior. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind trial was conducted at ambulatory care centers at the University of Minnesota (September 12, 2011, to June 15, 2012) and the University of Chicago (December 17, 2012, to June 26, 2015) and included 66 adults with SPD. Data analysis was performed from July 16 to September 9, 2015. INTERVENTIONS: N acetylcysteine (dosing range, 1200-3000 mg/d) or placebo was administered for 12 weeks. MAIN OUTCOMES AND MEASURES: Participants were assessed using measures of skin-picking severity, including the modified Yale-Brown Obsessive Compulsive Scale (NE-YBOCS); total scores range from 0 to 40, with higher scores reflective of greater symptom severity. Another measure of skin-picking severity was the Clinical Global Impression-Severity Scale; total scores range from 1 (normal) to 7 (among the most extremely ill patients), and improvement ratings range from 7 (very much worse) to 1 (very much improved). Selected cognitive tasks included the Intra-dimensional/Extra-dimensional Shift Task to examine cognitive flexibility, with the key outcome measures being the number of errors, and Stop Signal Reaction Time task, which evaluates motor inhibition. Outcomes were examined using a linear mixed-effects model. RESULTS: Of the 66 participants (31 randomized to placebo and 35 to N-acetylcysteine) included in the analysis, 59 (89%) were women; mean (SD) age was 34.8 (11.0) years. Compared with placebo, N acetylcysteine treatment was associated with significant improvements in the NE YBOCS. At baseline, NE-YBOCS scores were 18.9 and 17.9 for the treatment and placebo groups, respectively, and at 12 weeks, the scores were 11.5 and 14.1 for the treatment and placebo groups, respectively (P = .048). For the Clinical Global Impression-Severity scale, baseline scores were 3.5 and 4.0 and 12-week scores were 3.0 and 4.2, respectively (P = .003). These effects were significant both in terms of treatment by time interactions and post hoc tests at 1 or more individual time points. At the study's end point, of the 53 participants who completed the study, 15 of the 32 participants (47%) receiving N-acetylcysteine were much or very much improved compared with 4 of the 21 participants (19%) receiving placebo (P = .03). There were no significant differences between the active and placebo arms in terms of psychosocial functioning. CONCLUSIONS AND RELEVANCE: N-acetylcysteine treatment resulted in significant reductions in skin picking symptoms and was well tolerated. The glutamate system may prove a beneficial target in treating SPD and other compulsive behaviors. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01063348. PMID- 27007063 TI - Conjugated linoleic acids suppress inflammatory response and ICAM-1 expression through inhibition of NF-kappaB and MAPK signaling in human bronchial epithelial cells. AB - Conjugated linoleic acids (CLAs) comprise a group of natural unsaturated fatty acids. CLA was reported to have anti-asthma, anti-adiposity, and anti-tumor effects. The present study aimed to evaluate the suppressive effects of cis-9, trans-11-CLA (c9,t11-CLA) on the expression of proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) in TNF-alpha-stimulated human bronchial epithelial (BEAS-2B) cells. After treating with various doses of c9,t11 CLA (12.5-100 MUg ml(-1)), BEAS-2B cells were induced into an inflamed state by adding TNF-alpha or TNF-alpha/IL-4. The presence of c9,t11-CLA significantly suppressed the secretion of cytokines IL-6, IL-8, CCL5, and MCP-1. We also found that c9,t11-CLA inhibited ICAM-1 expression, and decreased monocyte adhesion to inflamed bronchial epithelial cells. Interestingly, c9,t11-CLA attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) and down-regulated the activation of nuclear factor-kappaB (NF-kappaB). These results suggested that the anti-inflammatory effects of c9,t11-CLA were mediated by inhibiting proinflammatory cytokines, chemokines, and ICAM-1 expression by blocking NF kappaB transcription regulation and by attenuating MAPK signaling pathways. PMID- 27007064 TI - Biographical disruption, adjustment and reconstruction of everyday occupations and work participation after mild traumatic brain injury. A focus group study. AB - PURPOSE: To explore traumatic brain injury (TBI) as a biographical disruption and to study the reconstruction of everyday occupations and work participation among individuals with mild TBI. METHODS: Seven focus groups were conducted with 12 women and 8 men (22-60 years) who had sustained mild TBI and participated in a return-to-work program. Interviews were analyzed using qualitative content analysis. RESULTS: Four interrelated themes emerged: disruption of occupational capacity and balance; changes in self-perceptions; experience of time; and occupational adjustment and reconstruction. The meaning of the impairments lies in their impact on the individual's everyday occupations. The abandonment of meaningful daily occupations and the feeling of not recognizing oneself were experienced as threats to the sense of self. Successful integration of the past, present and future was paramount to continuing life activities. The unpredictability of the future seemed to permeate the entire process of adjustment and reconstruction of daily life. CONCLUSIONS: Our findings show that the concept of time is important in understanding and supporting the reconstruction of daily life after TBI. The fundamental work of rehabilitation is to ameliorate the disruptions caused by the injury, restoring a sense of personal narrative and supporting the ability to move forward with life. Implications for Rehabilitation Individuals with a protracted recovery after a mild traumatic brain injury must reconstruct a new way of being and acting in the world to achieve biographical continuity. The perceived anxiety regarding changes in self and occupational identity, as well as loss of control over the future, can be attenuated through informational sessions during the hospital stay and at follow up visits. The significant personal costs of returning to full-time employment too early indicate the need for early and ongoing vocational support in achieving a successful return to work. PMID- 27007065 TI - mHealth intervention to improve medication management in chronically ill patients: analysis of the recruitment process. AB - OBJECTIVES: Mobile phones have been rapidly adopted by the general population and are now a promising technology with considerable potential in health care. However, refusal rates of 24%-75% have been reported in telemedicine studies. We aimed to report the challenges faced when recruiting patients to use Android and iOS smartphone applications aimed at improving medication management and communication between patients and healthcare professionals. METHODS: The patients invited to participate had heart failure and/or hypertension and/or dyslipidemia. After reaching the number of participants required for inclusion, the recruitment process was analyzed, and the study team determined the reasons for refusal. RESULTS: Of the 448 potential participants who were invited to participate, 210 responded. Of these, 37.1% did not use a smartphone, 2.9% owned a mobile phone that was neither iOS nor Android, and 28.6% were smartphone users who refused to participate. In this case, the most common motive was that patients considered their routine healthcare sufficient and had no trouble remembering to take their medicines (81.7%). The final study sample comprised 48 patients. The mean age of the patients enrolled was significantly lower than that of participants who were not included (59.9 +/- 10.6 vs. 66.8 +/- 11.4 years, respectively; p=0.00). CONCLUSION: We found age to be an important barrier to smartphone use in healthcare. Among smartphone users, good adherence and sufficient routine healthcare were the most common reasons for refusal to participate. Thus, this type of intervention could enhance participation for poor adherers or caregivers. Implementing educational initiatives could play a key role in improving patient perceptions of technology. PMID- 27007066 TI - Addition of posttraumatic stress and sensory hypersensitivity more accurately estimates disability and pain than fear avoidance measures alone after whiplash injury. AB - The fear avoidance model (FAM) has been proposed to explain the development of chronic disability in a variety of conditions including whiplash-associated disorders (WADs). The FAM does not account for symptoms of posttraumatic stress and sensory hypersensitivity, which are associated with poor recovery from whiplash injury. The aim of this study was to explore a model for the maintenance of pain and related disability in people with WAD including symptoms of PTSD, sensory hypersensitivity, and FAM components. The relationship between individual components in the model and disability and how these relationships changed over the first 12 weeks after injury were investigated. We performed a longitudinal study of 103 (74 female) patients with WAD. Measures of pain intensity, cold and mechanical pain thresholds, symptoms of posttraumatic stress, pain catastrophising, kinesiophobia, and fear of cervical spine movement were collected within 6 weeks of injury and at 12 weeks after injury. Mixed-model analysis using Neck Disability Index (NDI) scores and average 24-hour pain intensity as the dependent variables revealed that overall model fit was greatest when measures of fear of movement, posttraumatic stress, and sensory hypersensitivity were included. The interactive effects of time with catastrophising and time with fear of activity of the cervical spine were also included in the best model for disability. These results provide preliminary support for the addition of neurobiological and stress system components to the FAM to explain poor outcome in patients with WAD. PMID- 27007067 TI - Pain phenotype as a predictor for drug response in painful polyneuropathy-a retrospective analysis of data from controlled clinical trials. AB - The drugs available for treatment of neuropathic pain have somewhat disappointing efficacy with many patients left with limited or no effect. Individualized treatment based on phenotype according to presumed underlying pain mechanism(s) has been proposed to improve outcomes. We report a retrospective analysis of phenotype-specific effects of several neuropathic pain drugs, which were studied in a series of crossover, placebo-controlled, clinical trials. The data originate from 7 trials with similar design and outcome recordings, which all had a thorough baseline registration of symptoms, signs, and quantitative sensory testing. The latter was used to phenotype patients into subgroups reflecting presumed pain mechanisms. There were a total of 361 patient records distributed over treatments with 4 antidepressants and 4 anticonvulsants. Five of the drugs reduced total pain significantly compared with placebo. Only a few phenotype specific differences in total pain reduction were found within the investigated drugs. Thus, imipramine reduced total pain 1.84 (CI: 0.02-3.67) and pregabalin 0.81 (CI: -0.67 to 2.29) in patients with than without gain of sensory function. Pregabalin showed a better effect in patients with preserved large fiber function with a mean difference in total pain reduction 1.31 (CI: 0.15-2.47). No phenotype specific effects were found for venlafaxine, escitalopram, oxcarbazepine, valproic acid, levetiracetam, or St. John's wort. Thus, this post hoc analysis of 8 drugs with mainly nonselective actions on neuropathic pain mechanisms found limited usefulness of sensory phenotyping in pain as the basis for individualized treatment. PMID- 27007068 TI - Evidence for a central mode of action for etoricoxib (COX-2 inhibitor) in patients with painful knee osteoarthritis. AB - The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in patients with pain. This randomized, double-blind, placebo-controlled, 2-way crossover, 4-week treatment study investigated the pain mechanisms modulated by etoricoxib in patients with painful knee osteoarthritis. Patients were randomized to group A (60 mg/d etoricoxib followed by placebo) or B (placebo followed by 60 mg/d etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds, temporal summation (TS), and conditioning pain modulation. Clinical readouts were Brief Pain Inventory, WOMAC, painDETECT questionnaire (PD-Q), and time and pain intensity during walking and stair climbing. Etoricoxib as compared with placebo significantly modulated the pressure pain thresholds (P = 0.012, localized sensitization) at the knee and leg (control site) (P = 0.025, spreading sensitization) and TS assessed from the knee (P = 0.038) and leg (P = 0.045). Conditioning pain modulation was not modulated. The Brief Pain Inventory (pain scores), PD-Q, WOMAC, and walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0 day 28), responders and nonresponders were defined. The nonresponders showed a significant association between increased facilitation of TS and increased pain alleviation. None of the other parameters predicted the degree of pain alleviation. Generally, a responder to etoricoxib has the most facilitated TS. In conclusion, etoricoxib (1) modulated central pain modulatory mechanisms and (2) improved pain and function in painful osteoarthritis. Stronger facilitation of TS may indicate a better response to etoricoxib, supporting the central mode-of action of the drug. PMID- 27007069 TI - Processing of visual gravitational motion in the peri-sylvian cortex: Evidence from brain-damaged patients. AB - Rich behavioral evidence indicates that the brain estimates the visual direction and acceleration of gravity quite accurately, and the underlying mechanisms have begun to be unraveled. While the neuroanatomical substrates of gravity direction processing have been studied extensively in brain-damaged patients, to our knowledge no such study exists for the processing of visual gravitational motion. Here we asked 31 stroke patients to intercept a virtual ball moving along the vertical under either natural gravity or artificial reversed gravity. Twenty seven of them also aligned a luminous bar to the vertical direction (subjective visual vertical, SVV). Using voxel-based lesion-symptom mapping as well as lesion subtraction analysis, we found that lesions mainly centered on the posterior insula are associated with greater deviations of SVV, consistent with several previous studies. Instead, lesions mainly centered on the parietal operculum decrease the ability to discriminate natural from unnatural gravitational acceleration with a timed motor response in the interception task. Both the posterior insula and the parietal operculum belong to the vestibular cortex, and presumably receive multisensory information about the gravity vector. We speculate that an internal model estimating the effects of gravity on visual objects is constructed by transforming the vestibular estimates of mechanical gravity, which are computed in the brainstem and cerebellum, into internalized estimates of virtual gravity, which are stored in the cortical vestibular network. The present lesion data suggest a specific role for the parietal operculum in detecting the mismatch between predictive signals from the internal model and the online visual signals. PMID- 27007070 TI - Exploring involuntary childlessness in men - a qualitative study assessing quality of life, role aspects and control beliefs in men's perception of the fertility treatment process. AB - The goal of this study was to explore the experience and perception of men during the diagnosis of infertility and subsequent treatment, and the impact on role concepts, control beliefs, and quality of life on these processes. Furthermore, it aimed to derive improvements in how men should be counselled. A qualitative study was conducted. It consisted of 13 semi-structured individual interviews with men undergoing or about to start fertility treatment at Heidelberg University Hospital. Data were analyzed using a grounded theory approach. Men emphasized the rare opportunities for being involved in treatment, lack of control and the ambivalence of social support. Furthermore, their experiences differed enormously regarding the cause of infertility and the period for which they were preoccupied with the topic. Dealing with involuntary childlessness is challenging for all men. Nevertheless, participants revealed major differences in dealing with fertility treatment in relation to role concepts, control beliefs, social support and the cause of infertility. The significance of diverse causes of infertility and the need for men to adopt certain roles ought to be more valued and a holistic approach improving quality of life enhanced. PMID- 27007072 TI - Reduced Perinatal Leptin Availability May Contribute to Adverse Metabolic Programming in a Rat Model of Uteroplacental Insufficiency. AB - Leptin availability in perinatal life critically affects metabolic programming. We tested the hypothesis that uteroplacental insufficiency and intrauterine stress affect perinatal leptin availability in rat offspring. Pregnant rats underwent bilateral uterine vessel ligation (LIG; n = 14), sham operation (SOP; n = 12), or no operation (controls, n = 14). Fetal livers (n = 180), placentas (n = 180), and maternal blood were obtained 4 hours (gestational day [E] 19), 24 hours (E20), and 72 hours (E22) after surgery. In the offspring, we took blood samples on E22 (n = 44), postnatal day (P) 1 (n = 29), P2 (n = 16), P7 (n = 30), and P12 (n = 30). Circulating leptin (ELISA) was significantly reduced in LIG (E22, P1, P2) and SOP offspring (E22). Postnatal leptin surge was delayed in LIG but was accelerated in SOP offspring. Placental leptin gene expression (quantitative RT PCR) was reduced in LIG (E19, E20, E22) and SOP (E20, E22). Hepatic leptin receptor (Lepr-a, mediating leptin degradation) gene expression was increased in LIG fetuses (E20, E22) only. Surprisingly, hypoxia-inducible factors (Hif; Western blot) were unaltered in placentas and were reduced in the livers of LIG (Hif1a, E20; Hif2a, E19, E22) and SOP (Hif2a, E19) fetuses. Gene expression of prolyl hydroxylase 3, a factor expressed under hypoxic conditions contributing to Hif degradation, was increased in livers of LIG (E19, E20, E22) and SOP (E19) fetuses and in placentas of LIG and SOP (E19). In summary, reduced placental leptin production, increased fetal leptin degradation, and persistent perinatal hypoleptinemia are present in intrauterine growth restriction offspring, especially after uteroplacental insufficiency, and may contribute to perinatal programming of leptin resistance and adiposity in later life. PMID- 27007071 TI - Protein Restriction During the Last Third of Pregnancy Malprograms the Neuroendocrine Axes to Induce Metabolic Syndrome in Adult Male Rat Offspring. AB - Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID- 27007073 TI - Sexual Differentiation of Circadian Clock Function in the Adrenal Gland. AB - Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders. PMID- 27007074 TI - Evidence for Osteocalcin Binding and Activation of GPRC6A in beta-Cells. AB - The possibility that G protein-coupled receptor family C member A (GPRC6A) is the osteocalcin (Ocn)-sensing G protein-coupled receptor that directly regulates pancreatic beta-cell functions is controversial. In the current study, we found that Ocn and an Ocn-derived C-terminal hexapeptide directly activate GPRC6A dependent ERK signaling in vitro. Computational models probe the structural basis of Ocn binding to GPRC6A and predict that the C-terminal hexapeptide docks to the extracellular side of the transmembrane domain of GPRC6A. Consistent with the modeling, mutations in the computationally identified binding pocket of GPRC6A reduced Ocn and C-terminal hexapeptide activation of this receptor. In addition, selective deletion of Gprc6a in beta-cells (Gprc6a(beta)(-cell-cko)) by crossing Gprc6a(flox/flox) mice with Ins2-Cre mice resulted in reduced pancreatic weight, islet number, insulin protein content, and insulin message expression. Both islet size and beta-cell proliferation were reduced in Gprc6a(beta)(-cell-cko) compared with control mice. Gprc6a(beta)(-cell-cko) exhibited abnormal glucose tolerance, but normal insulin sensitivity. Islets isolated from Gprc6a(beta)(-cell-cko) mice showed reduced insulin simulation index in response to Ocn. These data establish the structural basis for Ocn direct activation of GPRC6A and confirm a role for GPRC6A in regulating beta-cell proliferation and insulin secretion. PMID- 27007075 TI - Long-Term Outcomes for Different Forms of Stress Cardiomyopathy After Surgical Treatment for Subarachnoid Hemorrhage. AB - BACKGROUND: Stress-induced cardiomyopathy (SCM) after subarachnoid hemorrhage (SAH) includes predominant apical or basal regional left ventricular dysfunction (RLVD) with concomitant changes in electrocardiogram or increase in cardiac enzymes. We hypothesized that difference in outcome is associated with the type of RLVD after SAH. METHODS: We studied a single-center retrospective cohort of SAH patients hospitalized between 2000 and 2010 with follow-up until 2013. We classified patients who had an echocardiogram for clinically indicated reasons according to the predominate location of RLVD as classic SCM-apical form and variant SCM-basal form. A Cox proportional hazard model and logistic regression were used to estimate the risk for death and hospital complications associated with different RLVD after adjustment for propensity to undergo echocardiography given clinical characteristics on admission. RESULTS: Among 715 SAH patients, 28% (200/715) had an echocardiogram for clinical evidence of cardiac dysfunction during hospitalization, the most common being acute left ventricular dysfunction, suspected acute ischemic event, changes in electrocardiogram and cardiac enzymes, and arrhythmia. SCM was present in 59 patients (8% of all cohort and 30% of patients with echocardiogram, respectively) with similar distribution of SCM basal (25/59) and SCM-apical forms (34/59). SAH patients who had an echocardiogram for clinically indicated reasons had a significantly decreased risk-adjusted long-term survival compared with those without an echocardiogram, regardless of the presence of RLVD. SCM-basal form was associated with cardiac complications (odds ratio, 6.1; 99% confidence interval, 1.8-20.2) and severe sepsis (odds ratio, 5.3; 99% confidence interval, 1.6-17.2). CONCLUSIONS: SAH patients with echocardiogram for a clinically indicated reason have a decreased long-term survival, regardless of the presence of RLVD. The association between severe sepsis and SCM-basal warrants future studies to determine their potential synergistic effect on left ventricular systolic dysfunction among SAH patients. PMID- 27007076 TI - The Risk of Falls After Total Knee Arthroplasty with the Use of a Femoral Nerve Block Versus an Adductor Canal Block: A Double-Blinded Randomized Controlled Study. AB - BACKGROUND: Adductor canal block (ACB) has emerged as an appealing alternative to femoral nerve block (FNB) that produces a predominantly sensory nerve block by anesthetizing the saphenous nerve. Studies have shown greater quadriceps strength preservation with ACB compared with FNB, but no advantage has yet been shown in terms of fall risk. The Tinetti scale is used by physical therapists to assess gait and balance, and total score can estimate a patient's fall risk. We designed this study to test the primary hypothesis that FNB results in a greater proportion of "high fall risk" patients postoperatively using the Tinetti score compared with ACB. METHODS: After institutional review board approval, informed written consent to participate in the study was obtained. Patients undergoing primary unilateral total knee arthroplasty were eligible for enrollment in this double-blind, randomized trial. Patients received either an ACB or FNB (20 mL of 0.5% ropivacaine) with catheter placement (8 mL/h of 0.2% ropivacaine) in the setting of multimodal analgesia. Continuous infusion was stopped in the morning of postoperative day (POD)1 before starting physical therapy (PT). On POD1, PT assessed the primary outcome using the Tinetti score for gait and balance. Patients were considered to be at high risk of falling if they scored <19. Secondary outcomes included manual muscle testing of the quadriceps muscle strength, Timed Up and Go (TUG) test, and ambulation distance on POD1 and POD2. The quality of postoperative analgesia and the quality of recovery were assessed with American Pain Society Patient Outcome Questionnaire Revised and Quality of Recovery-9 questionnaire, respectively. RESULTS: Sixty-two patients were enrolled in the study (31 ACB and 31 FNB). No difference was found in the proportion of "high fall risk" patients on POD1 (21/31 in the ACB group versus 24/31 in the FNB group [P = 0.7]; relative risk, 1.14 [95% confidence interval, 0.84-1.56]) or POD2 (7/31 in the ACB versus 14/31 in the FNB group [P = 0.06]; relative risk, 2.0 [95% confidence interval, 0.94-4.27]). The average distance of ambulation during PT and time to up and go were similar on POD1 and POD2. Manual muscle testing grades were significantly higher on POD1 in the ACB group when compared with that in the FNB (P = 0.001) (Wilcoxon-Mann-Whitney odds, 2.25 [95% confidence interval, 1.35-4.26]). There were no other differences in postoperative outcomes. CONCLUSIONS: ACB results in greater preservation of quadriceps muscle strength. Although we did not detect a significant reduction in fall risk when compared with FNB, based on the upper limit of the relative risk, it may very well be present. Further study is needed with a larger sample size. PMID- 27007078 TI - The Relationship Between Oxygen Reserve Index and Arterial Partial Pressure of Oxygen During Surgery. AB - BACKGROUND: The use of intraoperative pulse oximetry (SpO2) enhances hypoxia detection and is associated with fewer perioperative hypoxic events. However, SpO2 may be reported as 98% when arterial partial pressure of oxygen (PaO2) is as low as 70 mm Hg. Therefore, SpO2 may not provide advance warning of falling arterial oxygenation until PaO2 approaches this level. Multiwave pulse co oximetry can provide a calculated oxygen reserve index (ORI) that may add to information from pulse oximetry when SpO2 is >98%. This study evaluates the ORI to PaO2 relationship during surgery. METHODS: We studied patients undergoing scheduled surgery in which arterial catheterization and intraoperative arterial blood gas analysis were planned. Data from multiple pulse co-oximetry sensors on each patient were continuously collected and stored on a research computer. Regression analysis was used to compare ORI with PaO2 obtained from each arterial blood gas measurement and changes in ORI with changes in PaO2 from sequential measurements. Linear mixed-effects regression models for repeated measures were then used to account for within-subject correlation across the repeatedly measured PaO2 and ORI and for the unequal time intervals of PaO2 determination over elapsed surgical time. Regression plots were inspected for ORI values corresponding to PaO2 of 100 and 150 mm Hg. ORI and PaO2 were compared using mixed-effects models with a subject-specific random intercept. RESULTS: ORI values and PaO2 measurements were obtained from intraoperative data collected from 106 patients. Regression analysis showed that the ORI to PaO2 relationship was stronger for PaO2 to 240 mm Hg (r = 0.536) than for PaO2 over 240 mm Hg (r = 0.0016). Measured PaO2 was >=100 mm Hg for all ORI over 0.24. Measured PaO2 was >=150 mm Hg in 96.6% of samples when ORI was over 0.55. A random intercept variance component linear mixed-effects model for repeated measures indicated that PaO2 was significantly related to ORI (beta[95% confidence interval] = 0.002 [0.0019-0.0022]; P < 0.0001). A similar analysis indicated a significant relationship between change in PaO2 and change in ORI (beta [95% confidence interval] = 0.0044 [0.0040-0.0048]; P < 0.0001). CONCLUSIONS: These findings suggest that ORI >0.24 can distinguish PaO2 >=100 mm Hg when SpO2 is over 98%. Similarly, ORI > 0.55 appears to be a threshold to distinguish PaO2 >=150 mm Hg. The usefulness of these values should be evaluated prospectively. Decreases in ORI to near 0.24 may provide advance indication of falling PaO2 approaching 100 mm Hg when SpO2 is >98%. The clinical utility of interventions based on continuous ORI monitoring should be studied prospectively. PMID- 27007077 TI - Low-Fidelity Haptic Simulation Versus Mental Imagery Training for Epidural Anesthesia Technical Achievement in Novice Anesthesiology Residents: A Randomized Comparative Study. AB - BACKGROUND: There are many teaching methods for epidural anesthesia skill acquisition. Previous work suggests that there is no difference in skill acquisition whether novice learners engage in low-fidelity (LF) versus high fidelity haptic simulation for epidural anesthesia. No study, however, has compared the effect of LF haptic simulation for epidural anesthesia versus mental imagery (MI) training in which no physical practice is attempted. We tested the hypothesis that MI training is superior to LF haptic simulation training for epidural anesthesia skill acquisition. METHODS: Twenty Post-Graduate Year 2 (PGY 2) anesthesiology residents were tested at the beginning of the training year. After a didactic lecture on epidural anesthesia, they were randomized into 2 groups. Group LF had LF simulation training for epidural anesthesia using a previously described banana simulation technique. Group MI had guided, scripted MI training in which they initially were oriented to the epidural kit components and epidural anesthesia was described stepwise in detail, followed by individual mental rehearsal; no physical practice was undertaken. Each resident then individually performed epidural anesthesia on a partial-human task trainer on 3 consecutive occasions under the direct observation of skilled evaluators who were blinded to group assignment. Technical achievement was assessed with the use of a modified validated skills checklist. Scores (0-21) and duration to task completion (minutes) were recorded. A linear mixed-effects model analysis was performed to determine the differences in scores and duration between groups and over time. RESULTS: There was no statistical difference between the 2 groups for scores and duration to task completion. Both groups showed similarly significant increases (P = 0.0015) in scores over time (estimated mean score [SE]: group MI, 15.9 [0.55] to 17.4 [0.55] to 18.6 [0.55]; group LF, 16.2 [0.55] to 17.7 [0.55] to 18.9 [0.55]). Time to complete the procedure decreased similarly and significantly (P = 0.032) for both groups after the first attempt (estimated mean time [SE]: group MI, 16.0 [1.04] minutes to 13.7 [1.04] minutes to 13.3 [1.04] minutes; group LF: 15.8 [1.04] minutes to 13.4 [1.04] minutes to 13.1 [1.04] minutes). CONCLUSIONS: MI is not different from LF simulation training for epidural anesthesia skill acquisition. Education in epidural anesthesia with structured didactics and continual MI training may suffice to prepare novice learners before an attempt on human subjects. PMID- 27007080 TI - Semisupervised Gaussian Process for Automated Enzyme Search. AB - Synthetic biology is today harnessing the design of novel and greener biosynthesis routes for the production of added-value chemicals and natural products. The design of novel pathways often requires a detailed selection of enzyme sequences to import into the chassis at each of the reaction steps. To address such design requirements in an automated way, we present here a tool for exploring the space of enzymatic reactions. Given a reaction and an enzyme the tool provides a probability estimate that the enzyme catalyzes the reaction. Our tool first considers the similarity of a reaction to known biochemical reactions with respect to signatures around their reaction centers. Signatures are defined based on chemical transformation rules by using extended connectivity fingerprint descriptors. A semisupervised Gaussian process model associated with the similar known reactions then provides the probability estimate. The Gaussian process model uses information about both the reaction and the enzyme in providing the estimate. These estimates were validated experimentally by the application of the Gaussian process model to a newly identified metabolite in Escherichia coli in order to search for the enzymes catalyzing its associated reactions. Furthermore, we show with several pathway design examples how such ability to assign probability estimates to enzymatic reactions provides the potential to assist in bioengineering applications, providing experimental validation to our proposed approach. To the best of our knowledge, the proposed approach is the first application of Gaussian processes dealing with biological sequences and chemicals, the use of a semisupervised Gaussian process framework is also novel in the context of machine learning applied to bioinformatics. However, the ability of an enzyme to catalyze a reaction depends on the affinity between the substrates of the reaction and the enzyme. This affinity is generally quantified by the Michaelis constant KM. Therefore, we also demonstrate using Gaussian process regression to predict KM given a substrate-enzyme pair. PMID- 27007079 TI - The Recovery Time of Myometrial Responsiveness After Oxytocin-Induced Desensitization in Human Myometrium In Vitro. AB - BACKGROUND: Postpartum hemorrhage secondary to uterine atony is a leading cause of maternal morbidity. Prolonged exposure to oxytocin for labor augmentation can result in the desensitization phenomenon, a decrease in the responsiveness of myometrium to further oxytocin. It is currently not known whether waiting for a specific time interval after the cessation of oxytocin allows the oxytocin receptors to resensitize and recover, thereby improving subsequent oxytocin induced myometrial contractility. We aimed to investigate the effect of a rest period of 30, 60, and 90 minutes after oxytocin administration on the recovery of oxytocin-desensitized human myometrium in vitro. We hypothesized that the longer the rest period, the better the responsiveness and subsequent oxytocin-induced contractility of the myometrium. METHODS: Myometrial tissue was obtained from women undergoing elective cesarean deliveries. The myometrial sample was dissected into 4 strips, and each strip was mounted in a single organ bath with physiological salt solution (PSS) under homeostatic conditions and then pretreated for 2 hours with oxytocin 10 M. After pretreatment, each strip was washed with PSS and allowed to rest in PSS solution for 30, 60, or 90 minutes. At the end of the rest period, dose-response testing to oxytocin 10 to 10 M was performed. A control group consisted of oxytocin dose-response testing without any oxytocin pretreatment. Contractile parameters were measured and compared among the groups after square root transformation. The primary outcome was motility index (frequency * amplitude), and secondary outcomes included frequency, amplitude, and area under the curve. RESULTS: Fifty-five experiments were conducted from samples obtained from 16 women. The mean motility index (?g.contractions/10 min) during the dose-response curve (oxytocin 10 to 10 M) in the control group was significantly greater than all the experimental groups; the mean estimated differences (95% confidence intervals) were -1.33 (-2.50 to -0.15, P = 0.02), -1.59 (-2.68 to -0.50, P = 0.004), and -1.88 (-2.97 to -0.80, P = 0.001) for the 30-, 60-, and 90-minute groups, respectively. When the experimental groups were compared, there were no significant differences in any of the contractility parameters; however, confidence intervals were wide. CONCLUSIONS: Our study shows that oxytocin pretreatment attenuates oxytocin induced contractility in human myometrium despite a rest period of up to 90 minutes after oxytocin administration. However, we were unable to determine whether increasing the rest period from 30 to 90 minutes results in improvement in myometrial contractility because of our small sample size relative to the variability in the contractile parameters. Further laboratory and clinical in vivo studies are necessary to determine whether a rest period up to 90 minutes results in improvement in myometrial contractility. In addition, further experimental studies are necessary to determine the key mechanisms of oxytocin receptor resensitization. PMID- 27007081 TI - Ternary Model of the Speciation of I-/Br-/Cl-Trihalomethanes Formed in Chloraminated Surface Waters. AB - This study examined the effects of the iodide concentration and pH on yields and speciation of the entire group of 10 species of iodine-, bromine-, and chlorine containing trihalomethanes (THMs) formed at pH values from 6.5 to 8.5 in chloraminated surface waters in the presence of bromide and iodide. Pathways of iodine, bromine, and chlorine incorporation in the active sites in dissolved organic matter (DOM) were examined on the basis of a ternary halogenation/THM speciation model. The model assumed the occurrence of sequential three-step halogenation of the active site and competition of iodine, bromine, and chlorine species at each node of the halogenation sequence. A comparison of experimentally measured and modeled speciation coefficients and also iodine and bromine incorporation factors calculated for 10 THM species showed that the developed approach was sufficient to closely model the observed trends. Interpretation of preferred iodine incorporation pathways associated with the generation of THMs in all examined conditions showed that the susceptibility of the halogenated intermediates to iodine incorporation increases rapidly with the number of iodine atoms that have already been incorporated into the reaction site. In contrast, the incorporation of bromine and chlorine atoms in the intermediates involved in the generation of THMs makes them largely inactive in iodine incorporation reactions. The presented approach allows for a further understanding of the mechanisms of DOM/halogen interactions and prediction of the speciation of THMs formed at varying pH values, iodide concentrations, and other system conditions. PMID- 27007083 TI - Forward-Osmosis Desalination with Poly(Ionic Liquid) Hydrogels as Smart Draw Agents. AB - The combination of high desalination efficiency, negligible draw-solute leakage, nontoxicity, ease of regeneration, and effective separation to produce liquid water makes the smart draw agents developed here highly suited for forward osmosis desalination. PMID- 27007084 TI - Detection of PIK3CA mutations, including a novel mutation of V344G in exon 4, in metastatic lung adenocarcinomas: A retrospective study of 115 FNA cases. AB - BACKGROUND: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations and amplification are detected in 1% of primary lung adenocarcinomas (ADCs) and in 38% of primary lung squamous cell carcinomas. Alterations of PIK3CA in metastatic non-small cell lung carcinoma (NSCLC), however, are still not fully understood. This study investigated PIK3CA alterations in metastatic ADCs and correlated the findings with those for other commonly tested molecular abnormalities via fine-needle aspiration (FNA) and small-core biopsy materials. METHODS: This study identified 115 FNA cases of metastatic lung ADC with standard lung cancer panel analysis by targeted next generation sequencing and fluorescence in situ hybridization at the Johns Hopkins Medical Institute over a 12-month period. The panel included mutational analysis of PIK3CA, AKT, BRAF, EGFR, ERBB2, KRAS, and NRAS genes and tests of rearrangements for ALK and ROS1 genes. RESULTS: A PIK3CA mutation was detected in 7 of 115 cases of metastatic ADC (6.1%). The majority of the mutations were located in exon 9 or exon 20; however, a mutation in exon 1 was seen in 1 case. Furthermore, p.V344G in exon 4 was detected in 2 cases. Among cases with PIK3CA mutations, 4 had coexisting EGFR mutations, whereas 2 had a coexisting BRAF or KRAS mutation. CONCLUSIONS: Several common mutations as well as a novel mutation in the PIK3CA gene were observed in metastatic NSCLC (particularly ADC). The unique role, however, of PIK3CA mutations in metastatic NSCLC and the clinical implications need to be further investigated. Cancer Cytopathol 2016;124:485-92. (c) 2016 American Cancer Society. PMID- 27007085 TI - Sex hormones and systemic inflammation are modulators of the obese-asthma phenotype. AB - BACKGROUND: Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese-asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill (OCP) use, systemic inflammation and airway inflammation in adults with asthma. METHODS: Obese (n = 39) and nonobese (n = 42) females and obese (n = 24) and nonobese (n = 25) males with asthma were recruited. Females were further categorized as reproductive-aged (<50 years old; n = 36) or older (>50 years old; n = 45). Thirteen (36.1%) reproductive-aged females were using the OCP. Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers. RESULTS: Obese reproductive-aged females had higher sputum %neutrophils than nonobese reproductive-aged females (45.4 +/- 24.3% vs 27.5 +/- 17.5%, P = 0.016); however, there was no difference in sputum neutrophils in obese compared with nonobese males (P = 0.620) or older females (P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C-reactive protein and IL-6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive-aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 +/- 12.6% vs 42.1 +/- 23.8%, P = 0.015). CONCLUSIONS: This study suggests that sex hormones and systemic inflammation may be mediating the obese-asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive-aged females warrants further investigation. PMID- 27007086 TI - Caregiver fatigue and surrogate end-of-life decision making. PMID- 27007088 TI - Teaching surgery takes time: the impact of surgical education on time in the operating room. AB - BACKGROUND: It is generally accepted that surgical training is associated with increased surgical duration. The purpose of this study was to determine the magnitude of this increase for common surgical procedures by comparing surgery duration in teaching and nonteaching hospitals. METHODS: This retrospective population-based cohort study included all adult residents of Ontario, Canada, who underwent 1 of 14 surgical procedures between 2002 and 2012. We used several linked administrative databases to identify the study cohort in addition to patient-, surgeon- and procedure-related variables. We determined surgery duration using anesthesiology billing records. Negative binomial regression was used to model the association between teaching versus nonteaching hospital status and surgery duration. RESULTS: Of the 713 573 surgical cases included in this study, 20.8% were performed in a teaching hospital. For each procedure, the mean surgery duration was significantly longer for teaching hospitals, with differences ranging from 5 to 62 minutes across individual procedures in unadjusted analyses (all p < 0.001). In regression analysis, procedures performed in teaching hospitals were associated with an overall 22% (95% confidence interval 20%-24%) increase in surgery duration, adjusting for patient-, surgeon- and procedure-related variables as well as the clustering of patients within surgeons and hospitals. CONCLUSION: Our results show that a wide range of surgical procedures require significantly more time to perform in teaching than nonteaching hospitals. Given the magnitude of this difference, the impact of surgical training on health care costs and clinical outcomes should be a priority for future studies. PMID- 27007089 TI - Laparoscopic sleeve gastrectomy at a new bariatric surgery centre in Canada: 30 day complication rates using the Clavien-Dindo classification. AB - BACKGROUND: Newfoundland and Labrador (NL) has the highest rate of obesity in Canada, prompting the establishment of a bariatric surgery program at the Health Sciences Centre in NL. This retrospective study examined 30-day complication rates in more than 200 consecutive patients who underwent laparoscopic sleeve gastrectomy (LSG) between May 2011 and February 2014. METHODS: We performed a chart review and collected data on 30-day postoperative complications. Complications were graded and reported using the Clavien-Dindo classification. Grades I and II were defined as minor and grades III and higher were defined as major complications. RESULTS: We reviewed the charts of the first 209 patients to undergo LSG. The mean body mass index was 49.2, 81% were women and the average age was 43 years. Comorbidities included hypertension (55.0%), obstructive sleep apnea (46.4%), dyslipidemia (42.1%), diabetes (37.3%), osteoarthritis (36.4%) and cardiovascular disease with previous cardiac stents (5.3%). Furthermore, 38.3% of patients reported psychiatric diagnoses, such as depression and anxiety. The overall 30-day complication rate was 15.3%. The complication rate for minor complications was 13.4% and for major complications was 1.9% (2 leaks, 1 stricture and 1 fistula). CONCLUSION: Our results support the feasibility of safely performing LSG surgery at bariatric centres completing fewer than 125 procedures annually. PMID- 27007091 TI - Are patients willing to pay for total shoulder arthroplasty? Evidence from a discrete choice experiment. AB - BACKGROUND: Total shoulder arthroplasty (TSA) is a common treatment to decrease pain and improve shoulder function in patients with severe osteoarthritis (OA). In Canada, patients requiring this procedure often wait a year or more. Our objective was to determine patient preferences related to accessing TSA, specifically comparing out-of-pocket payments for treatment, travel time to hospital, the surgeon's level of experience and wait times. METHODS: We administered a discrete choice experiment among patients with endstage shoulder OA currently waiting for TSA. Respondents were presented with 14 different choice sets, each with 3 options, and they were asked to choose their preferred scenario. A conditional logit regression model was used to estimate the relative preference and willingness to pay for each attribute. RESULTS: Sixty-two respondents completed the questionnaire. Three of the 4 attributes significantly influenced treatment preferences. Respondents had a strong preference for an experienced surgeon (mean 0.89 +/- standard error [SE] 0.11), while reductions in travel time (-0.07 +/- 0.04) or wait time (-0.04 +/- 0.01) were of less importance. Respondents were found to be strongly averse (-1.44 +/- 0.18) to surgical treatment by a less experienced surgeon and to paying out-of-pocket for their surgical treatment (-0.56 +/- 0.05). CONCLUSION: Our results suggest that patients waiting for TSA to treat severe shoulder OA have minimal willingness to pay for a reduction in wait time or travel time for surgery, yet will pay higher amounts for treatment by an experienced surgeon. PMID- 27007090 TI - A Canadian population-based description of the indications for lower-extremity amputations and outcomes. AB - BACKGROUND: To our knowledge, there have been no previously published reports characterizing lower-extremity amputations in Canada. The objective of this study was to describe the indications and outcomes of lower-extremity amputations in the Canadian population. METHODS: We performed a retrospective cohort study of all adult patients who underwent lower-extremity amputation in Canada between 2006 and 2009. Patients were identified from the Canadian Institute for Health Information's Discharge Abstract Database, which includes all hospital admissions across Canada with the exception of the province of Quebec. Pediatric, trauma, and outpatients were excluded. RESULTS: During the study period, 5342 patients underwent lower-extremity amputations in 207 Canadian hospitals. The mean age was 67 +/- 13 years, and 68% were men. Amputations were most frequently indicated after admission for diabetic complications (81%), cardiovascular disease (6%), or cancer (3%). In total, 65% of patients were discharged to another inpatient or long-term care facility, and 26% were discharged home with or without extra support. Most patients were diabetic (96%) and most (65%) required a below-knee amputation. Predictors of prolonged (> 7 d) hospital stay included amputation performed by a general surgeon; cardiovascular risk factors, such as diabetes, hypertension, ischemic heart disease, congestive heart failure, or hyperlipidemia; and undergoing the amputation in the provinces of Newfoundland and Labrador, New Brunswick, or British Columbia. CONCLUSION: There is variability in the delivery of lower-extremity amputations and postoperative hospital discharges among surgical specialists and regions across Canada. Future work is needed to investigate the reasons for this variability and to develop initiatives to shorten postoperative hospital stays. PMID- 27007092 TI - The relevance of preoperative ultrasound cervical mapping in patients with thyroid cancer. AB - BACKGROUND: Cervical lymph node involvement in thyroid cancer is associated with locoregional recurrence and decreased disease-free survival. Preoperative lymph node mapping helps in planning surgery for neck dissection and improves patient outcomes. We sought to perform a qualitative and quantitative analysis of ultrasound mapping for thyroid cancer and evaluate the clinical importance of this exam in terms of identifying the group of patients who would benefit most from subsequent surgical dissection. METHODS: We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery between 2009 and 2013. We calculated the positive predictive values (PPVs) of ultrasound mapping of both the lateral and central compartments together and the lateral or central compartment individually. A quantitative analysis was performed by comparing the number of positive lymph nodes at ultrasound imaging with histopathologic evaluation. RESULTS: A total of 136 cases of thyroid cancer in 120 patients met the inclusion criteria for ultrasound mapping analysis. The PPVs (and 95% confidence intervals) were 83.82 (0.76-0.89) for the lateral and central compartments, 85.39% (0.76-0.91) for the lateral compartment, and 80.48% (0.7 0.87) for the central compartment. When comparing the positive lymph nodes at ultrasound imaging with histopathologic evaluation, the result was chi(2) = 10.33 (p = 0.006). CONCLUSION: This single-institution study indicated that preoperative ultrasound mapping is an accurate imaging procedure for predicting lymphatic spread in differentiated and medullary thyroid cancer. Ultrasound mapping can be used as an efficient tool for surgical planning and prognosis determination, as well as for identifying the group of patients who would benefit most from subsequent surgical intervention. PMID- 27007093 TI - Cross-cultural adaptation and validation of the Ankle Osteoarthritis Scale for use in French-speaking populations. AB - BACKGROUND: The Ankle Osteoarthritis Scale (AOS) is a self-administered score specific for ankle osteoarthritis (OA) with excellent reliability and strong construct and criterion validity. Many recent randomized multicentre trials have used the AOS, and the involvement of the French-speaking population is limited by the absence of a French version. Our goal was to develop a French version and validate the psychometric properties to assure equivalence to the original English version. METHODS: Translation was performed according to American Association of Orthopaedic Surgeons (AAOS) 2000 guidelines for cross-cultural adaptation. Similar to the validation process of the English AOS, we evaluated the psychometric properties of the French version (AOS-Fr): criterion validity (AOS-Fr v. Western Ontario and McMaster Universities Arthritis Index [WOMAC] and SF-36 scores), construct validity (AOS-Fr correlation to single heel-lift test), and reliability (AOS-Fr test-retest). Sixty healthy individuals tested a prefinal version of the AOS-Fr for comprehension, leading to modifications and a final version that was approved by C. Saltzman, author of the AOS. We then recruited patients with ankle OA for evaluation of the AOS-Fr psychometric properties. RESULTS: Twenty-eight patients with ankle OA participated in the evaluation. The AOS-Fr showed strong criterion validity (AOS:WOMAC r = 0.709 and AOS:SF-36 r = 0.654) and construct validity (r = 0.664) and proved to be reliable (test-retest intraclass correlation coefficient = 0.922). CONCLUSION: The AOS-Fr is a reliable and valid score equivalent to the English version in terms of psychometric properties, thus is available for use in multicentre trials. PMID- 27007095 TI - Dr. William Waugh (1851-1936): promoter of change in nineteenth century medical education and practice. AB - SUMMARY: Dr. William E. Waugh (1851-1936) witnessed and actively participated in many changes in medical education and practice during his 6 decades in medicine. Trained as a surgeon and general practitioner, Waugh practised medicine in London, Ont., during the late nineteenth and early twentieth centuries. Early in his career, he embraced the new field of microbiology; refused outdated practices, such as bleeding; and dared to form a medical school despite strong criticism. Waugh was one of the founders of the Western University medical school, and he served various teaching and administrative roles in addition to maintaining a successful practice. He reminded students of the role of the physician's senses, which he cautioned were in danger of being eclipsed, rather than supplemented, by the diagnostic instruments being adopted into clinical practice. PMID- 27007096 TI - Apples and oranges. PMID- 27007094 TI - Clinical practice guideline: management of acute pancreatitis. AB - ABSTRACT: There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality. Despite the availability of clinical practice guidelines for the management of acute pancreatitis, recent studies auditing the clinical management of the condition have shown important areas of noncompliance with evidence-based recommendations. This underscores the importance of creating understandable and implementable recommendations for the diagnosis and management of acute pancreatitis. The purpose of the present guideline is to provide evidence-based recommendations for the management of both mild and severe acute pancreatitis as well as the management of complications of acute pancreatitis and of gall stone-induced pancreatitis. PMID- 27007097 TI - Apples and oranges: Author response. PMID- 27007098 TI - Letter to the Editor. PMID- 27007099 TI - Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: a cohort study. AB - PURPOSE: The association between extracorporeal membrane oxygenation (ECMO) use and the development of thrombocytopenia is widely presumed yet weakly demonstrated. We hypothesized that longer duration of ECMO support would be independently associated with worsened thrombocytopenia. METHODS: We performed a single-center retrospective cohort study of 100 adults who received ECMO for acute respiratory failure. We used generalized estimating equations to test the association between days on ECMO and daily percentage of platelets compared to the first post-cannulation platelet count. We constructed a multivariable logistic regression model with backwards stepwise elimination to identify clinical predictors of severe thrombocytopenia (<=50,000/MUL) while on ECMO. RESULTS: Days on ECMO was not associated with a decrease in platelet count in the unadjusted analysis (beta -0.85, 95 % CI -2.05 to 0.36), nor after considering and controlling for days hospitalized prior to ECMO, APACHE II score, platelet transfusions, and potential thrombocytopenia-inducing medications (beta -0.83, 95 % CI -1.9 to 0.25). Twenty-two subjects (22 %) developed severe thrombocytopenia. The APACHE II score and platelet count at the time of cannulation predicted the development of severe thrombocytopenia. The odds of developing severe thrombocytopenia increased 35 % for every 5-point increase in APACHE II score (OR 1.35, 95 % CI 0.94-1.94) and increased 35 % for every 25,000/MUL platelets below a mean at cannulation of 188,000/MUL (OR 1.35, 95 % CI 1.10-1.64). CONCLUSIONS: Duration of ECMO is not associated with the development of thrombocytopenia. The severity of critical illness and platelet count at the time of cannulation predict the development of severe thrombocytopenia while receiving ECMO for respiratory failure. Future studies should validate these findings, especially in cohorts with more venoarterial ECMO patients, and should characterize the association between thrombocytopenia and bleeding events while on ECMO. PMID- 27007100 TI - Does my patient really have ARDS? PMID- 27007101 TI - Is the literature inconclusive about the harm from HES? No. PMID- 27007102 TI - Is the literature inconclusive about the harm from HES? Yes. PMID- 27007103 TI - Is the literature inconclusive about the harm of HES? We are not sure. PMID- 27007104 TI - The Berlin definition met our needs: no. PMID- 27007105 TI - The Berlin definition met our needs: yes. PMID- 27007106 TI - The Berlin definition met our needs: not sure. PMID- 27007107 TI - Brain injury during venovenous extracorporeal membrane oxygenation. AB - PURPOSE: The frequency of neurological events and their impact on patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) are unknown. We therefore study the epidemiology, risk factors, and impact of cerebral complications occurring in VV-ECMO patients. METHODS: Observational study conducted in a tertiary referral center (2006-2012) on patients developing a neurological complication (ischemic stroke or intracranial bleeding) while on VV ECMO versus those who did not, and a systematic review on this topic. RESULTS: Among 135 consecutive patients who had received VV-ECMO, 18 (15 assessable) developed cerebral complications on ECMO: cerebral bleeding in 10 (7.5 %), ischemic stroke in 3 (2 %), or diffuse microbleeds in 2 (2 %), occurring after respective medians (IQR) of 3 (1-11), 21 (10-26), and 36 (8-63) days post-ECMO onset. Intracranial bleeding was independently associated with renal failure at intensive care unit admission and rapid PaCO2 decrease at ECMO initiation, but not with age, comorbidities, or hemostasis disorders. Seven (70 %) patients with intracranial bleeding and one (33 %) with ischemic stroke died versus 40 % of patients without neurological event. A systematic review found comparable intracranial bleeding rates (5 %). CONCLUSIONS: Neurological events occurred frequently in patients on VV-ECMO. Intracranial bleeding, the most frequent, occurred early and was associated with higher mortality. Because it was independently associated with rapid hypercapnia decrease, the latter should be avoided at ECMO onset, but its exact role remains to be determined. These findings may have major implications for the care of patients requiring VV-ECMO. PMID- 27007108 TI - Venovenous extracorporeal membrane oxygenation for acute respiratory failure : A clinical review from an international group of experts. AB - Despite expensive life-sustaining interventions delivered in the ICU, mortality and morbidity in patients with acute respiratory failure (ARF) remain unacceptably high. Extracorporeal membrane oxygenation (ECMO) has emerged as a promising intervention that may provide more efficacious supportive care to these patients. Improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARF. A greater appreciation of the complications associated with the placement of an artificial airway and mechanical ventilation has led clinicians and researchers to seek viable alternatives to providing supportive care in these patients. Thus, this review will summarize the current knowledge regarding the use of venovenous (VV)-ECMO for ARF and describe some of the recent controversies in the field, such as mechanical ventilation, anticoagulation and transfusion therapy, and ethical concerns in patients supported with VV-ECMO. PMID- 27007109 TI - Development and validation of the pediatric risk estimate score for children using extracorporeal respiratory support (Ped-RESCUERS). AB - PURPOSE: To develop and validate the Pediatric Risk Estimation Score for Children Using Extracorporeal Respiratory Support (Ped-RESCUERS). Ped-RESCUERS is designed to estimate the in-hospital mortality risk for children prior to receiving respiratory extracorporeal membrane oxygenation (ECMO) support. METHODS: This study used data from an international registry of patients aged 29 days to less than 18 years who received ECMO support from 2009 to 2014. We divided the registry into development and validation datasets by calendar date. Candidate variables were selected for model inclusion if the variable independently changed the mortality risk by at least 2 % in a Bayesian logistic regression model with in-hospital mortality as the outcome. We characterized the model's ability to discriminate mortality with the area under curve (AUC) of the receiver operating characteristic. RESULTS: From 2009 to 2014, 2458 non-neonatal children received ECMO for respiratory support, with a mortality rate of 39.8 %. The development dataset contained 1611 children receiving ECMO support from 2009 to 2012. The model included the following variables: pre-ECMO pH, pre-ECMO arterial partial pressure of carbon dioxide, hours of intubation prior to ECMO support, hours of admission at ECMO center prior to ECMO support, ventilator type, mean airway pressure, pre-ECMO use of milrinone, and a diagnosis of pertussis, asthma, bronchiolitis, or malignancy. The validation dataset included 438 children receiving ECMO support from 2013 to 2014. The Ped-RESCUERS model from the development dataset had an AUC of 0.690, and the validation dataset had an AUC of 0.634. CONCLUSIONS: Ped-RESCUERS provides a novel measure of pre-ECMO mortality risk. Future studies should seek external validation and improved discrimination of this mortality prediction tool. PMID- 27007110 TI - Can we prevent intubation in patients with ARDS? PMID- 27007111 TI - Diagnostic workup for ARDS patients. AB - Acute respiratory distress syndrome (ARDS) is defined by the association of bilateral infiltrates and hypoxaemia following an initial insult. Although a new definition has been recently proposed (Berlin definition), there are various forms of ARDS with potential differences regarding their management (ventilator settings, prone positioning use, corticosteroids). ARDS can be caused by various aetiologies, and the adequate treatment of the responsible cause is crucial to improve the outcome. It is of paramount importance to characterize the mechanisms causing lung injury to optimize both the aetiological treatment and the symptomatic treatment. If there is no obvious cause of ARDS or if a direct lung injury is suspected, bronchoalveolar lavage (BAL) should be strongly considered to identify microorganisms responsible for pneumonia. Blood samples can also help to identify microorganisms and to evaluate biomarkers of infection. If there is no infectious cause of ARDS or no other apparent aetiology is found, second-line examinations should include markers of immunologic diseases. In selected cases, open lung biopsy remains useful to identify the cause of ARDS when all other examinations remain inconclusive. CT scan is fundamental when there is a suspicion of intra-abdominal sepsis and in some cases of pneumonia. Ultrasonography is important not only in evaluating biventricular function but also in identifying pleural effusions and pneumothorax. The definition of ARDS remains clinical and the main objective of the diagnostic workup should be to be focused on identification of its aetiology, especially a treatable infection. PMID- 27007112 TI - Community Size Effects on Epidemic Spreading in Multiplex Social Networks. AB - The dynamical process of epidemic spreading has drawn much attention of the complex network community. In the network paradigm, diseases spread from one person to another through the social ties amongst the population. There are a variety of factors that govern the processes of disease spreading on the networks. A common but not negligible factor is people's reaction to the outbreak of epidemics. Such reaction can be related information dissemination or self protection. In this work, we explore the interactions between disease spreading and population response in terms of information diffusion and individuals' alertness. We model the system by mapping multiplex networks into two-layer networks and incorporating individuals' risk awareness, on the assumption that their response to the disease spreading depends on the size of the community they belong to. By comparing the final incidence of diseases in multiplex networks, we find that there is considerable mitigation of diseases spreading for full phase of spreading speed when individuals' protection responses are introduced. Interestingly, the degree of community overlap between the two layers is found to be critical factor that affects the final incidence. We also analyze the consequences of the epidemic incidence in communities with different sizes and the impacts of community overlap between two layers. Specifically, as the diseases information makes individuals alert and take measures to prevent the diseases, the effective protection is more striking in small community. These phenomena can be explained by the multiplexity of the networked system and the competition between two spreading processes. PMID- 27007113 TI - Aquatic exercise for the treatment of knee and hip osteoarthritis. AB - BACKGROUND: Osteoarthritis is a chronic disease characterized by joint pain, tenderness, and limitation of movement. At present, no cure is available. Thus only treatment of the person's symptoms and treatment to prevent further development of the disease are possible. Clinical trials indicate that aquatic exercise may have advantages for people with osteoarthritis. This is an update of a published Cochrane review. OBJECTIVES: To evaluate the effects of aquatic exercise for people with knee or hip osteoarthritis, or both, compared to no intervention. SEARCH METHODS: We searched the following databases up to 28 April 2015: the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library Issue 1, 2014), MEDLINE (from 1949), EMBASE (from 1980), CINAHL (from 1982), PEDro (Physiotherapy Evidence Database), and Web of Science (from 1945). There was no language restriction. SELECTION CRITERIA: Randomized controlled clinical trials of aquatic exercise compared to a control group (e.g. usual care, education, social attention, telephone call, waiting list for surgery) of participants with knee or hip osteoarthritis. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed risk of bias of the included trials. We analysed the pooled results using standardized mean difference (SMD) values. MAIN RESULTS: Nine new trials met the inclusion criteria and we excluded two earlier included trials. Thus the number of participants increased from 800 to 1190 and the number of included trials increased from six to 13. Most participants were female (75%), with an average age of 68 years and a body mass index (BMI) of 29.4. Osteoarthritis duration was 6.7 years, with a great variation of the included participants. The mean aquatic exercise duration was 12 weeks. We found 12 trials at low to unclear risk of bias for all domains except blinding of participants and personnel. They showed that aquatic exercise caused a small short term improvement compared to control in pain (SMD -0.31, 95% CI -0.47 to -0.15; 12 trials, 1076 participants) and disability (SMD -0.32, 95% CI -0.47 to -0.17; 12 trials, 1059 participants). Ten trials showed a small effect on quality of life (QoL) (SMD -0.25, 95% CI 0.49 to -0.01; 10 trials, 971 participants). These effects on pain and disability correspond to a five point lower (95% CI three to eight points lower) score on mean pain and mean disability compared to the control group (scale 0 to 100), and a seven point higher (95% CI 0 to 13 points higher) score on mean QoL compared with control group (scale 0 to 100). No included trials performed a radiographic evaluation. No serious adverse events were reported in the included trials with relation to aquatic exercise. AUTHORS' CONCLUSIONS: There is moderate quality evidence that aquatic exercise may have small, short-term, and clinically relevant effects on patient-reported pain, disability, and QoL in people with knee and hip OA. The conclusions of this review update does not change those of the previous published version of this Cochrane review. PMID- 27007114 TI - High Frequencies of Anti-Host Reactive CD8+ T Cells Ignore Non-Hematopoietic Antigen after Bone Marrow Transplantation in a Murine Model. AB - BACKGROUND: Graft versus host disease (GvHD) occurs in 20% of cases with patients having an MHC I matched bone marrow transplantation (BMT). Mechanisms causing this disease remain to be studied. METHODS: Here we used a CD8+ T cell transgenic mouse line (P14/CD45.1+) and transgenic DEE mice bearing ubiquitously the glycoprotein 33-41 (GP33) antigen derived from the major lymphocytic choriomeningitis virus (LCMV) epitope to study mechanisms of tolerance in anti host reactive CD8+ T cells after BMT. RESULTS: We found that anti-host reactive CD8+ T cells (P14 T cells) were not negatively selected in the thymus and that they were present in wild type (WT) recipient mice as well as in DEE recipient mice. Anti-host reactive CD8+ T cells ignored the GP33 antigen expressed ubiquitously by host cells but they could be activated ex vivo via LCMV infection. Lipopolysaccharides (LPS) induced transient cell damage in DEE mice bearing anti-host reactive CD8+ T cells after BMT, suggesting that induction of host inflammatory response could break antigen ignorance. Introducing the GP33 antigen into BM cells led to deletion of anti-host reactive CD8+ T cells. CONCLUSION: We found that after BMT anti-host reactive CD8+ T cells ignored host antigen in recipients and that they were only deleted when host antigen was present in hematopoietic cells. Moreover, LPS-induced immune activation contributed to induction of alloreactivity of anti-host reactive CD8+ T cells after BMT. PMID- 27007117 TI - The Effects of Community Attachment and Information Seeking on Displaced Disaster Victims' Decision Making. AB - This paper uses original survey data of the Great East Japan earthquake disaster victims to examine their decision to apply for the temporary housing as well as the timing of application. We assess the effects of victims' attachment to their locality as well as variation in victims' information seeking behavior. We additionally consider various factors such as income, age, employment and family structure that are generally considered to affect the decision to choose temporary housing as victims' solution for their displacement. Empirical results indicate that, ceteris paribus, as the degree of attachment increases, victims are more likely to apply for the temporary housing but attachment does not affect the timing of application. On the other hand, the victims who actively seek information and are able to collect higher quality information are less likely to apply for the temporary housing and if they do apply then they apply relatively later. PMID- 27007116 TI - Ultrastructural and Molecular Characterisation of an Heterosporis-Like Microsporidian in Australian Sea Snakes (Hydrophiinae). AB - Four sea snakes (two Hydrophis major, one Hydrophis platurus, one Hydrophis elegans) were found washed ashore on different beaches in the Sunshine Coast region and Fraser Island in Queensland, Australia between 2007-2013. Each snake had multiple granulomas and locally extensive regions of pallor evident in the hypaxial and intercostal musculature along the body. Lesions in two individuals were also associated with vertebral and rib fractures. Histological examination revealed granulomas scattered throughout skeletal muscle, subcutaneous adipose tissue and fractured bone. These were composed of dense aggregates of microsporidian spores surrounded by a mantle of macrophages. Sequences (ssrRNA) were obtained from lesions in three sea snakes and all revealed 99% similarity with Heterosporis anguillarum from the Japanese eel (Anguillarum japonica). However, ultrastructural characteristics of the organism were not consistent with those of previous descriptions. Electron microscopic examination of skeletal muscle revealed large cysts (not xenomas) bound by walls of fibrillar material (Heterosporis-like sporophorocyst walls were not detected). The cysts contained numerous mature microsporidian spores arranged in small clusters, sometimes apparently within sporophorous vesicles. The microspores were monomorphic, oval and measured 2.5-3.0 MUm by 1.6-1.8 MUm. They contained isofilar polar filaments with 11 (infrequently 9-12) coils arranged in two ranks. This is the first published report of a microsporidian infection in hydrophiid sea snakes. This discovery shows microsporidia with molecular affinities to Heterosporis anguillarum but ultrastructural characters most consistent with the genus Pleistophora (but no hitherto described species). Further studies are required to determine whether the microsporidian presented here belongs to the genus Heterosporis, or to a polymorphic species group as suggested by the recognition of a robust Pleistophora/Heterosporis clade by molecular studies. The gross and histological pathology associated with these infections are described. PMID- 27007115 TI - Ionomycin Treatment Renders NK Cells Hyporesponsive. AB - Natural killer cells are cytotoxic lymphocytes important in immune responses to cancer and multiple pathogens. However, chronic activation of NK cells can induce a hyporesponsive state. The molecular basis of the mechanisms underlying the generation and maintenance of this hyporesponsive condition are unknown, thus an easy and reproducible mechanism able to induce hyporesponsiveness on human NK cells would be very useful to gain understanding of this process. Human NK cells treated with ionomycin lose their ability to degranulate and secrete IFN-gamma in response to a variety of stimuli, but IL-2 stimulation can compensate these defects. Apart from reductions in the expression of CD11a/CD18, no great changes were observed in the activating and inhibitory receptors expressed by these NK cells, however their transcriptional signature is different to that described for other hyporesponsive lymphocytes. PMID- 27007118 TI - A Comparison of the Adaptive Immune Response between Recovered Anthrax Patients and Individuals Receiving Three Different Anthrax Vaccines. AB - Several different human vaccines are available to protect against anthrax. We compared the human adaptive immune responses generated by three different anthrax vaccines or by previous exposure to cutaneous anthrax. Adaptive immunity was measured by ELISPOT to count cells that produce interferon (IFN)-gamma in response to restimulation ex vivo with the anthrax toxin components PA, LF and EF and by measuring circulating IgG specific to these antigens. Neutralising activity of antisera against anthrax toxin was also assayed. We found that the different exposures to anthrax antigens promoted varying immune responses. Cutaneous anthrax promoted strong IFN-gamma responses to all three antigens and antibody responses to PA and LF. The American AVA and Russian LAAV vaccines induced antibody responses to PA only. The British AVP vaccine produced IFN-gamma responses to EF and antibody responses to all three antigens. Anti-PA (in AVA and LAAV vaccinees) or anti-LF (in AVP vaccinees) antibody titres correlated with toxin neutralisation activities. Our study is the first to compare all three vaccines in humans and show the diversity of responses against anthrax antigens. PMID- 27007120 TI - Erratum to: Neonatal Junctional Epidermolysis Bullosa: Treatment Conundrums and Ethical Decision Making. PMID- 27007121 TI - Contributions of self-report and performance-based individual differences measures of social cognitive ability to large-scale neural network functioning. AB - Adaptive social behavior appears to require flexible interaction between multiple large-scale brain networks, including the executive control network (ECN), the default mode network (DMN), and the salience network (SN), as well as interactions with the perceptual processing systems these networks function to modulate. Highly connected cortical "hub" regions are also thought to facilitate interactions between these networks, including the dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and anterior insula (AI). However, less is presently known about the relationship between these network functions and individual differences in social-cognitive abilities. In the present study, 23 healthy adults (12 female) underwent functional magnetic resonance imaging (fMRI) while performing a visually based social judgment task (requiring the evaluation of social dominance in faces). Participants also completed both self-report and performance-based measures of emotional intelligence (EI), as well as measures of personality and facial perception ability. During scanning, social judgment, relative to a control condition involving simple perceptual judgment of facial features in the same stimuli, activated hub regions associated with each of the networks mentioned above (observed clusters included: bilateral DLPFC, DMPFC/ACC, AI, and ventral visual cortex). Interestingly, self-reported and performance-based measures of social-cognitive ability showed opposing associations with these patterns of activation. Specifically, lower self-reported EI and lower openness in personality both independently predicted greater activation within hub regions of the SN, DMN, and ECN (i.e., the DLPFC, DMPFC/ACC, and AI clusters); in contrast, in the same analyses greater scores on performance-based EI measures and on facial perception tasks independently predicted greater activation within hub regions of the SN and ECN (the DLPFC and AI clusters), and also in the ventral visual cortex. These findings suggest that lower confidence in one's own social cognitive abilities may promote the allocation of greater cognitive resources to, and improve the performance of, social-cognitive functions. PMID- 27007119 TI - Identification of protease m1 zinc metalloprotease conferring resistance to deltamethrin by characterization of an AFLP marker in Culex pipiens pallens. AB - BACKGROUND: Continuous and excessive application of deltamethrin (DM) has resulted in the rapid development of insecticide resistance in Culex pipiens pallens. The quantitative trait loci (QTL) responsible for resistance to DM had previously been detected in Cx. pipiens pallens. But locating the QTLs on the chromosomes remained difficult. An available approach is to first characterize DNA molecular markers linked with the phenotype, and then identify candidate genes. METHODS: In this study, the amplified fragment length polymorphism (AFLP) marker L3A8.177 associated with the QTL, was characterized. We searched for potential candidate genes in the flank region of L3A8.177 in the genome sequence of the closely related Cx. pipiens quinquefasciatus and conducted mRNA expression analysis of the candidate gene via quantitative real-time PCR. Then the relationship between DM resistance and the candidate gene was identified using RNAi and American CDC Bottle Bioassay in vivo. We also cloned the ORF sequences of the candidate gene from both susceptible and resistant mosquitoes. RESULTS: The genes CYP6CP1 and protease m1 zinc metalloprotease were in the flank region of L3A8.177 and had significantly different expression levels between susceptible and resistant strains. Protease m1 zinc metalloprotease was significantly up regulated in the susceptible strains compared with the resistant and remained over-expressed in the susceptible field-collected strains. For deduced amino acid sequences of protease m1 zinc metalloprotease, there was no difference between susceptible and resistant mosquitoes. Knockdown of protease m1 zinc metalloprotease not only decreased the sensitivity of mosquitoes to DM in the susceptible strain but also increased the expression of CYP6CP1, suggesting the role of protease m1 zinc metalloprotease in resistance may be involved in the regulation of the P450 gene expression. CONCLUSION: Our study represents an example of candidate genes derived from the AFLP marker associated with the QTL and provides the first evidence that protease m1 zinc metalloprotease may play a role in the regulation of DM resistance in Cx. pipiens pallens. PMID- 27007122 TI - Terrestrial Mammal Occupancy in the Context of Widespread Forest Loss and a Proposed Interoceanic Canal in Nicaragua's Decreasingly Remote South Caribbean Region. AB - Central America is experiencing rapid forest loss and habitat degradation both inside and outside of protected areas. Despite increasing deforestation, the Caribbean region of Nicaragua plays an important role in the survival or extinction of large mammal populations in Central America given that it still retains core areas of habitat for large mammal species. The proposed interoceanic canal project that would bisect the southern half of this Caribbean region represents a new threat that, combined with an advancing agricultural frontier, could affect populations of large mammal species such as jaguars, white-lipped peccaries, and Baird's tapirs. We used occupancy models to examine the relative occupancy probabilities for an assemblage of terrestrial mammals in the south Caribbean region of Nicaragua to identify current core areas for our study species and conduct a preliminary evaluation of the potential impacts of the proposed interoceanic canal. We modeled a community level distribution of eight species with varying levels of sensitivity to human encroachment and a range of habitat associations. Our model results reveal three priority areas for terrestrial mammal conservation in our study area. The mapped predictions show that the only remaining area of suitable habitat for large mammals in the path of the proposed interoceanic canal is a relatively thin strip of forest that runs along the Caribbean Coast. In light of these findings, we propose five recommendations that will help ensure the conservation of this area of the proposed canal route as suitable habitat for our study species. PMID- 27007124 TI - Social Capital and the Paradox of Poor but Healthy Groups in the United States. AB - Increased income strongly correlates with improved health and lower mortality risk. Yet in spite of having a lower mean and median income, both Hispanics and the foreign-born living within the U.S. have higher longevity compared with native-born, non-Hispanics. We explored the role of structural social capital in conferring protection against poor health outcomes among Hispanics and the foreign-born in the US. We used the National Health and Nutrition Examination Survey III 1988-1994 linked to prospective mortality follow up to examine the relationship between five measures of structural social capital and: (1) intermediate health outcomes (blood pressure, plasma fibrinogen, C-reactive protein, and total cholesterol) and (2) a distal outcome (all cause mortality). The foreign-born and Hispanics generally had lower measures of structural social capital relative to native-born non-Hispanics. Additionally, while structural social capital was protective against poor health or mortality among native-born persons, the association disappeared for Hispanics and the foreign-born. PMID- 27007123 TI - The Brd4 acetyllysine-binding protein is involved in activation of polyomavirus JC. AB - Brd4 is an epigenetic reader protein and a member of the BET (bromodomain and extra terminal domain) family of proteins with two bromodomains that recognize acetylated lysine residues. Brd4 specifically binds to acetylated transcription factor NF-kappaB p65 and coactivates transcription. Polyomavirus JC (JCV) is regulated by a noncoding control region (NCCR) containing promoter/enhancer elements for viral gene expression including a binding site for NF-kappaB, which responds to proinflammatory cytokines such as TNF-alpha, the DNA damage response, calcium signaling and acetylation of the NF-kappaB p65 subunit on lysine residues K218 and K221. Earlier studies indicated that NF-kappaB is involved in the reactivation of persistent/latent JCV in glial cells to cause progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the brain caused by replication of JCV in glial cells. To investigate the mechanism of action of NF-kappaB acetylation on JCV transcription, we examined Brd4 and found that JCV early transcription was stimulated by Brd4 via the JCV NF-kappaB site and that p65 K218 and K221 were involved. Treatment with the Brd4 inhibitor JQ1(+) or mutation of either K218 or K221 to glutamine (K218R or K221) inhibited this stimulation and decreased the proportion of p65 in the nucleus. We conclude that Brd4 is involved in the regulation of the activation status of JCV in glial cells. PMID- 27007125 TI - The Final Frontier-Transitions and Sustainability: From Mentored to Independent Research. AB - A recurrent theme in much of the contemporary HIV behavioral and social science research is that ecological approaches that acknowledge the interplay of structural, institutional, and individual-level factors are essential to improve HIV prevention efforts in racial/ethnic minority communities. Similarly, an ecological approach provides an innovative framework for understanding the challenges that many racial/ethnic minority HIV prevention researchers face in their quest to transition from mentored researcher to independent researchers. Informed by an ecological framework, and building on our experiences as two racial/ethnic minority women HIV prevention researchers who transitioned from a formal research mentorship relationship to become independent HIV prevention researchers-principal investigators of NIH-funded R01 grants-, we frame our discussion of the mentored to independence research trajectory with a focus on structural, institutional, and individual determinants. Throughout, we integrate suggestions for how institutions, mentors, and HIV prevention researchers can facilitate the final frontier from mentored research to independence. PMID- 27007126 TI - The Role of Sonic Hedgehog Signaling in Osteoclastogenesis and Jaw Bone Destruction. AB - Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of its expression appear to correlate with disease progression and metastasis. However, the role of SHH in bone destruction associated with oral squamous cell carcinomas is still unclear. In this study we analyzed SHH expression and the role played by SHH signaling in gingival carcinoma-induced jawbone destruction. From an analysis of surgically resected lower gingival squamous cell carcinoma mandible samples, we found that SHH was highly expressed in tumor cells that had invaded the bone matrix. On the other hand, the hedgehog receptor Patched and the signaling molecule Gli-2 were highly expressed in the osteoclasts and the progenitor cells. SHH stimulated osteoclast formation and pit formation in the presence of the receptor activator for nuclear factor-kappaB ligand (RANKL) in CD11b+ mouse bone marrow cells. SHH upregulated phosphorylation of ERK1/2 and p38 MAPK, NFATc1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K expression in RAW264.7 cells. Our results suggest that tumor-derived SHH stimulated the osteoclast formation and bone resorption in the tumor jawbone microenvironment. PMID- 27007128 TI - F-18-FDG-avid lymph node metastasis along preferential lymphatic drainage pathways from the tumor-bearing lung lobe on F-18-FDG PET/CT in patients with non small-cell lung cancer. AB - OBJECTIVE: F-18-FDG-avid lymph node (LN) metastasis may preferentially occur along the lymphatic drainage pathway (LDP) from the tumor-bearing lobe in patients with non-small cell lung cancer (NSCLC) on FDG PET/CT. This study evaluated whether the identification of metastatic LNs according to LDP-based visual image interpretation can improve LN staging on FDG PET/CT in these patients. METHODS: FDG PET/CT study was performed in 265 patients with NSCLC. The presence and LN station of metastatic LNs were determined by surgery or the clinical course. In the LDP-based interpretation, FDG-avid LNs, which were located along the preferential LDP from each tumor-bearing lobe and visually more intense in FDG uptake compared with the remaining LNs straying away from the preferential LDP, were diagnosed as metastatic. The result was compared with the quantitative method using a cutoff value of 2.5 for the maximum standardized uptake value. RESULTS: Of the total 1031 mediastinal and hilar LN stations with FDG-avid LNs in 265 patients, 179 stations in 66 patients were metastatic and the remaining 852 were benign. All the metastatic LN stations except for 2 stations showing skip metastasis were located along the main preferential LDP or another preferential LDP via a direct anatomic pathway from each tumor-bearing lung lobe. The specificity, accuracy, and PPV for identifying metastatic LN stations by LDP based interpretation were 97.9, 95.7 and 89.5 %, respectively, which were significantly greater compared with those of 92.7, 90.8 and 70.3 % by the SUV based method (P < 0.001). CONCLUSIONS: The present study shows that FDG-avid LN metastasis preferentially occurs along the LDP from the tumor-bearing lobe in NSCLC patients. LDP-based visual image interpretation on FDG PET/CT can improve LN staging in these patients. PMID- 27007127 TI - Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice. AB - Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis) is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFbeta, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care) with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data. PMID- 27007129 TI - Pharmacokinetics and pharmacogenetics of Gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. AB - Gemcitabine is an antimetabolite ranking among the most prescribed anticancer drugs worldwide. This nucleoside analog exerts its antiproliferative action after tumoral conversion into active triphosphorylated nucleotides interfering with DNA synthesis and targeting ribonucleotide reductase. Gemcitabine is a mainstay for treating pancreatic and lung cancers, alone or in combination with several cytotoxic drugs (nab-paclitaxel, cisplatin and oxaliplatin), and is an option in a variety of other solid or hematological cancers. Several determinants of response have been identified with gemcitabine, i.e., membrane transporters, activating and inactivating enzymes at the tumor level, or Hedgehog signaling pathway. More recent studies have investigated how germinal genetic polymorphisms affecting cytidine deaminase, the enzyme responsible for the liver disposition of gemcitabine, could act as well as a marker for clinical outcome (i.e., toxicity, efficacy) at the bedside. Besides, constant efforts have been made to develop alternative chemical derivatives or encapsulated forms of gemcitabine, as an attempt to improve its metabolism and pharmacokinetics profile. Overall, gemcitabine is a drug paradigmatic for constant searches of the scientific community to improve its administration through the development of personalized medicine in oncology. PMID- 27007130 TI - Long-term follow-up after "one-shot" CO2 laser stapedotomy: is the functional outcome stable during the years? AB - The use of "one-shot" CO2 laser technique for a primary small-fenestra stapedotomy is well established, but few papers report the long-term functional results. We retrospectively reviewed medical records of 198 patients, treated for otosclerosis from January 2008 to December 2011, at the Department of Head and Neck Surgery, Catholic University of Rome. Statistical comparison between audiological thresholds obtained 24 h preoperatively, at early (4 weeks) and late postoperative examinations (mean time 45 months), was performed. Comparison of preoperative vs both early and late postoperative ACPTA showed a statistically significant difference (respectively 55 vs 33 and 31 dB; p < 0.001). No statistical difference was observed between preoperative, early and late postoperative BCPTA (respectively 23 vs 23 and 22 dB; p > 0.05). Both early and late postoperative ABG improved significantly compared to the preoperative one (respectively 10 and 9 vs 32 dB; p < 0.001). No statistical difference was found in comparison of early vs late postoperative ACPTA (respectively 33 vs 31 dB; p > 0.05), early vs late postoperative ABG (respectively 10 vs 9 dB; p > 0.05) and early vs late ABG gain (respectively 22 vs 23 dB; p > 0.05). No subjects developed postoperative complications requiring revision surgery or late deterioration of hearing threshold. The analysis of our data suggests that "one shot" CO2 laser stapedotomy is an effective and safe procedure: it allows a rapid stapedotomy without damages for the inner ear and optimal functional results that remain stable during the years. PMID- 27007131 TI - A comparison of electrothermal bipolar vessel sealing system and electrocautery in selective neck dissection. AB - The use of LigaSureTM vessel sealing system in head and neck surgery was reported to be reliable and safe, providing sufficient hemostasis and reducing operating time. The aim of this study was to evaluate efficacy of this technique in patients undergoing selective neck dissections. This study was carried out as a prospective controlled study at an otolaryngology department of a tertiary medical center between July 2013 and July 2015. Twenty-five patients older than 18 years who underwent unilateral selective neck dissection for head and neck cancer were included in the study. In the control group (group 2, 10 patients) only monopolar and bipolar diathermy was used; in the Ligasure group (group 1, 15 patients) Ligasure was used for hemostasis and dissection in addition to the conventional techniques. Cervical lymphadenectomy time, operation time, preoperative hemoglobin levels, preoperative hematocrit levels, postoperative hemoglobin levels, postoperative hematocrit levels, total neck drainage and drain removal time were analyzed and compared between the groups. Median operation time in group 1 and 2 were 95 min (IQR = 35) and 142.5 min (IQR = 63), respectively. Median cervical lymphadenectomy time in group 1 and 2 were 55 min (IQR = 23) and 102.5 min (IQR = 49), respectively. Median operation time and cervical operation time were significantly lower in group 1 (p < 0.05). In conclusion, LigaSureTM vessel sealing system is a safe, efficacious technique and significantly lowers cervical lymphadenectomy and operation time in selective neck dissections compared to controls. Given the superb hemostatic properties, this technique should be in the surgeon's armamentarium when possible. PMID- 27007133 TI - Implementation of human thermal comfort information in Koppen-Geiger climate classification-the example of China. AB - Koppen-Geiger climate classification (KGC) is accepted and applied worldwide. The climatic parameters utilised in KGC, however, cannot indicate human thermal comfort (HTC) conditions or air humidity (AH) conditions directly, because they are originally based on climatic effects on vegetation, instead of that on human body directly. In addition, HTC is driven by meteorological parameters together. Thus, the objective of this study is to preliminarily implement the HTC information and the AH information in KGC. Physiologically equivalent temperature (PET) has been chosen as the HTC index, and vapour pressure (VP) is for the quantification of AH conditions. In this preliminary study, 12 Chinese cities in total have been taken into account as the assumed representatives of 11 climate types. Basic meteorological data of each city with 3-h resolution in 2000-2012 has been analysed. RayMan model has been applied to calculate PET within the same time period. Each climate type has been described by frequencies of PET and frequencies of VP. For example, the Aw (Sanya) has the most frequent occurrence of thermally stressful conditions compared to other climate types: PET in 22 % points in time of the year was above 35 degrees C. The driest AH conditions existed in Dwc (Lhasa) and Dfb (Urumqi) with VP rarely above 18 hPa in the wettest month. Implementation of the HTC information and the additional AH information in each climate type of KGC can be helpful for the topics of human health, energy consumption, tourism, as well as urban planning. PMID- 27007132 TI - Voice outcomes of laryngopharyngeal reflux treatment: a systematic review of 1483 patients. AB - The aim of this study is to explore voice quality modifications in laryngopharyngeal reflux (LPR) disease and to understand better the pathophysiological mechanisms underlying the development of communicative disability. Biological Abstracts, BioMed Central, Cochrane database, PubMed and Scopus were assessed for subject headings using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations. Relevant studies published between January 1990 and December 2015 describing the evaluation of voice quality in LPR disease were retrieved. Issues of clinical relevance, such as LPR diagnosis method, treatment efficacy and outcomes, were evaluated for each study. We determined the grade of recommendation for each publication according to the Oxford Centre for Evidence-Based Medicine evidence levels. The search identified 145 publications, of which 25 studies met the inclusion criteria for a total of 1483 LPR patients. Data were extracted by 2 independent physicians who identified 16 trials with a IIb evidence level, 7 trials with a IIa evidence level and 2 RCTs with a Ib evidence level where 4 patient-based instruments and 5 clinician-based instruments were used. The main voice assessment outcomes reported were hoarseness assessments by physicians or patients, followed by acoustic parameters; 15 and 14 articles, respectively, demonstrated significant improvements in subjective and objective voice assessments after treatment. The methodology used to measure acoustic parameters (i.e. sustained vowel duration, the sample portion choice for measurement, etc.) varied from one study to another. The majority of studies indicated that voice quality assessments (especially acoustic parameters) remain an interesting outcome to measure the effectiveness of treatment, but further studies using standardised and transparent methodology to measure acoustic parameters are necessary to confirm the place of each tool in the LPR disease evaluation. PMID- 27007134 TI - Moderate Alcohol Use and Insulin Action in Chronic Hepatitis C Infection. AB - BACKGROUND AND AIM: Chronic hepatitis C (HCV) is associated with metabolic abnormalities including insulin resistance (IR) and diabetes. While moderate alcohol consumption is known to have beneficial metabolic effects in the general population, such potential effects in HCV are unknown. We aimed to assess the association between graded alcohol intake and IR, insulin secretion, and metabolic syndrome in HCV. METHODS: Ninety-five non-diabetic HCV-infected patients underwent detailed metabolic testing. IR was directly measured via steady-state plasma glucose (SSPG) during a 240-min insulin suppression test. Total insulin secretion and insulinogenic index were determined by 75-g oral glucose tolerance test. Genotyping of CYP2E1 was performed to detect genetic polymorphisms influencing alcohol metabolism. RESULTS: In this cohort, 61 % were abstinent from alcohol for the past 12 months, while 22 % were moderate, and 17 % heavy drinkers. Obesity and nonwhite ethnicity were the strongest predictors of IR. Moderate alcohol intake (vs none) was significantly associated with lower SSPG only among those with normal BMI (coef -72.9, 95 % CI -128.1 to -17.6, p = 0.01). Alcohol use was not associated with insulin secretion parameters when controlling for IR and other factors. Heavy alcohol intake (OR 3.2, 95 % CI 0.86 12.3) and nonwhite ethnicity (OR 7.1, 95 % CI 1.5-33.3) were associated with metabolic syndrome. Among nonwhites, the odds of metabolic syndrome were fivefold higher for heavy drinkers. CONCLUSIONS: Moderate alcohol intake is associated with improved insulin sensitivity in HCV, although this benefit was limited to normal-weight individuals. The potential benefit of moderate alcohol on IR and its metabolic consequences in HCV warrants further longitudinal investigation. PMID- 27007135 TI - Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy: A Multicenter Retrospective Study. AB - BACKGROUND: Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images. GOALS: Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels. STUDY: Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months. RESULTS: Overall, correlation between FC and LS was weak (r s: 0.232, P < 0.001). When two clinically significant FC thresholds (100 and 250 MUg/g) were examined, the r s between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS >= 135) or negative (LS < 135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 MUg/g with sensitivity 0.59 and specificity 0.41. LIMITATIONS: Retrospective design. CONCLUSIONS: LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level >= 76 MUg/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup. PMID- 27007136 TI - Reparation of Isoniazid and Rifampicin Combinatorial Therapy-Induced Hepatotoxic Effects by Bacopa monnieri. AB - Drug-induced liver injury is a major challenge in treating tuberculosis with isoniazid (INH) and rifampicin (RIF). This study was aimed at evaluating the protective effects of Bacopamonnieri (Brahmi) against INH and RIF-induced hepatotoxicity in a rat model and also to study the patterns of interaction between pregnane X receptor (PXR) and chosen active compounds of B. monnieri. Hepatotoxicity was induced in the experimental animals by the oral administration of INH and RIF (50 mg/kg b.w. each/day) for 28 days. The effects of co administration of B. monnieri (500 mg/kg b.w./day) in INH- and RIF-induced rats were studied by the estimation of biochemical analyses. The standard hepatoprotective drug silymarin (25 mg/kg b.w./day) was used for the purpose of comparison. In silico docking experiments were carried out using the PatchDock server and the results were analysed on the PyMol molecular viewer. There was significant reduction in the antioxidant status of INH and RIF-induced rats. Also, there was significant elevation in the levels of serum liver function markers in the INH- and RIF-induced rats. B. monnieri was able to normalise the tested parameters. In silico studies reveal significant interaction between PXR and bacopaside I. B. monnieri exerts significant protective effects against INH and RIF-induced hepatotoxicity in rats. PMID- 27007137 TI - Multiple Lytic Origins of Replication Are Required for Optimal Gammaherpesvirus Fitness In Vitro and In Vivo. AB - An unresolved question in herpesvirus biology is why some herpesviruses contain more than one lytic origin of replication (oriLyt). Using murine gammaherpesvirus 68 (MHV-68) as model virus containing two oriLyts, we demonstrate that loss of either of the two oriLyts was well tolerated in some situations but not in others both in vitro and in vivo. This was related to the cell type, the organ or the route of inoculation. Depending on the cell type, different cellular proteins, for example Hexim1 and Rbbp4, were found to be associated with oriLyt DNA. Overexpression or downregulation of these proteins differentially affected the growth of mutants lacking either the left or the right oriLyt. Thus, multiple oriLyts are required to ensure optimal fitness in different cell types and tissues. PMID- 27007146 TI - Rewriting the rules governing high intensity interactions of light with matter. AB - The trajectory of discovery associated with the study of high-intensity nonlinear radiative interactions with matter and corresponding nonlinear modes of electromagnetic propagation through material that have been conducted over the last 50 years can be presented as a landscape in the intensity/quantum energy [I homega] plane. Based on an extensive series of experimental and theoretical findings, a universal zone of anomalous enhanced electromagnetic coupling, designated as the fundamental nonlinear domain, can be defined. Since the lower boundaries of this region for all atomic matter correspond to homega ~ 10(3) eV and I ~ 10(16) W cm(-2), it heralds a future dominated by x-ray and gamma-ray studies of all phases of matter including nuclear states. The augmented strength of the interaction with materials can be generally expressed as an increase in the basic electromagnetic coupling constant in which the fine structure constant alpha -> Z(2)alpha, where Z denotes the number of electrons participating in an ordered response to the driving field. Since radiative conditions strongly favoring the development of this enhanced electromagnetic coupling are readily produced in self-trapped plasma channels, the processes associated with the generation of nonlinear interactions with materials stand in natural alliance with the nonlinear mechanisms that induce confined propagation. An experimental example involving the Xe (4d(10)5s(2)5p(6)) supershell for which Z ? 18 that falls in the specified anomalous nonlinear domain is described. This yields an effective coupling constant of Z(2)alpha ? 2.4 > 1, a magnitude comparable to the strong interaction and a value rendering as useless conventional perturbative analyses founded on an expansion in powers of alpha. This enhancement can be quantitatively understood as a direct consequence of the dominant role played by coherently driven multiply-excited states in the dynamics of the coupling. It is also conclusively demonstrated by an abundance of data that the utterly peerless champion of the experimental campaign leading to the definition of the fundamental nonlinear domain was excimer laser technology. The basis of this unique role was the ability to satisfy simultaneously a triplet (omega, I, P) of conditions stating the minimal values of the frequency omega, intensity I, and the power P necessary to enable the key physical processes to be experimentally observed and controllably combined. The historical confluence of these developments creates a solid foundation for the prediction of future advances in the fundamental understanding of ultra-high power density states of matter. The atomic findings graciously generalize to the composition of a nuclear stanza expressing the accessibility of the nuclear domain. With this basis serving as the launch platform, a cadenza of three grand challenge problems representing both new materials and new interactions is presented for future solution; they are (1) the performance of an experimental probe of the properties of the vacuum state associated with the dark energy at an intensity approaching the Schwinger/Heisenberg limit, (2) the attainment of amplification in the gamma-ray region (~1 MeV) and the discovery of a nuclear excimer, and (3) the determination of a path to the projected super-heavy nuclear island of stability. PMID- 27007138 TI - Integrated bioinformatics to decipher the ascorbic acid metabolic network in tomato. AB - Ascorbic acid is involved in a plethora of reactions in both plant and animal metabolism. It plays an essential role neutralizing free radicals and acting as enzyme co-factor in several reaction. Since humans are ascorbate auxotrophs, enhancing the nutritional quality of a widely consumed vegetable like tomato is a desirable goal. Although the main reactions of the ascorbate biosynthesis, recycling and translocation pathways have been characterized, the assignment of tomato genes to each enzymatic step of the entire network has never been reported to date. By integrating bioinformatics approaches, omics resources and transcriptome collections today available for tomato, this study provides an overview on the architecture of the ascorbate pathway. In particular, 237 tomato loci were associated with the different enzymatic steps of the network, establishing the first comprehensive reference collection of candidate genes based on the recently released tomato gene annotation. The co-expression analyses performed by using RNA-Seq data supported the functional investigation of main expression patterns for the candidate genes and highlighted a coordinated spatial temporal regulation of genes of the different pathways across tissues and developmental stages. Taken together these results provide evidence of a complex interplaying mechanism and highlight the pivotal role of functional related genes. The definition of genes contributing to alternative pathways and their expression profiles corroborates previous hypothesis on mechanisms of accumulation of ascorbate in the later stages of fruit ripening. Results and evidences here provided may facilitate the development of novel strategies for biofortification of tomato fruit with Vitamin C and offer an example framework for similar studies concerning other metabolic pathways and species. PMID- 27007147 TI - Two systems for empathy in obsessive-compulsive disorder: mentalizing and experience sharing. AB - Objective:: To investigate empathic abilities in patients with obsessive compulsive disorder (OCD) compared to control subjects. OCD is characterized by persistent obsessions and compulsions. Previous studies have proposed specific emotion recognition deficits in patients with OCD. The ability to recognize emotion is part of the broad construct of empathy that incorporates mentalizing and experience-sharing dimensions. Methods:: Twenty-four subjects with a diagnosis of OCD and 23 control subjects underwent empathic measures. Results:: Patients with OCD compared to control subjects showed deficits in all mentalizing measures. They were incapable of understanding the mental and emotional states of other people. On the other hand, in the sharing experience measures, the OCD group was able to empathize with the emotional experience of other people when they expressed emotions with positive valence, but were not able to do when the emotional valence was negative. Conclusion:: Our results suggest that patients with OCD show a difficulty in mentalizing ability, whereas the deficit in sharing ability is specific for the negative emotional valence. PMID- 27007148 TI - Neurobiological underpinnings of bipolar disorder focusing on findings of diffusion tensor imaging: a systematic review. AB - OBJECTIVE: To review the available data on diffusion tensor imaging (DTI) of subjects with bipolar disorder (BD), with a particular focus on fractional anisotropy (FA) in white matter (WM) tracts. METHODS: The PubMed/MEDLINE database was searched for relevant articles, which were included in a systematic review of the literature. FA reductions and WM abnormalities were divided anatomically into three groups: commissural tracts, association tracts, and projection tracts. RESULTS: Eighteen studies met the inclusion criteria. The corpus callosum was the main impaired commissural tract as demonstrated by FA reductions. Five studies reported FA reductions in the cingulum. Two studies reported decreased FA in the anterior thalamic radiation, and one in the corticospinal tract. Conversely, three studies found increased FA values in WM tracts involved in BD pathophysiology. CONCLUSION: Despite considerable heterogeneity, these results indicate a direct link between executive cognitive functioning and abnormal WM microstructural integrity of fronto-limbic tracts in patients with remitted BD, providing further evidence of the neuronal disruption that underlies BD symptomatology. PMID- 27007149 TI - Rnf25/AO7 positively regulates wnt signaling via disrupting Nkd1-Axin inhibitory complex independent of its ubiquitin ligase activity. AB - Wnt signaling components have been shown to control key events in embryogenesis and to maintain tissue homeostasis in the adult. Nkd1/2 and Axin1/2 protein families are required for feedback regulation of Wnt signaling. The mechanisms by which Nkd1 and Nkd2 exhibit significant differences in signal transduction remain incompletely understood. Here we report that Rnf25/AO7, a previously identified E3 ubiquitin ligase for Nkd2, physically interacts with Nkd1 and Axin in an E3 ligase-independent manner to strengthen Wnt signalling. To determine the biological role of Rnf25 in vivo, we found that the renal mesenchymal cell, in which rnf25 was knocked-down, also exhibited more epithelial characters than MOCK control. Meanwhile, the transcriptional level of rnf25 was elevated in three separate tumor tissues more than that in paracarcinomatous tissue. Depletion of Rnf25 in zebrafish embryos attenuated transcriptions of maternal and zygotic Wnt target genes. Our results indicated that Rnf25 might serve as a molecular device, controlling the different antagonizing functions against canonical Wnt signaling between Nkd1 and Nkd2 cooperated with Axin. PMID- 27007150 TI - DDX3 enhances oncogenic KRAS-induced tumor invasion in colorectal cancer via the beta-catenin/ZEB1 axis. AB - DDX3 plays a dual role in colorectal cancer; however, the role and underlying mechanism of DDX3 in colorectal tumorigenesis remains unclear. Here, we provide evidence that DDX3 enhances oncogenic KRAS transcription via an increase in SP1 binding to its promoter. Accelerating oncogenic KRAS expression by DDX3 promotes the invasion capability via the ERK/PTEN/AKT/beta-catenin cascade. Moreover, the beta-catenin/ZEB1 axis is responsible for DDX3-induced cell invasiveness and xenograft lung tumor nodule formation. The xenograft lung tumor nodules induced by DDX3-overexpressing T84 stable clone were nearly suppressed by the inhibitor of AKT (perifosine) or beta-catenin (XAV939). Among patients, high KRAS, positive nuclear beta-catenin expression and high ZEB1 were more commonly occurred in high DDX3 tumors than in low-DDX3 tumors. High-DDX3, high-KRAS, positive nuclear beta catenin tumors, and high-ZEB1 exhibited worse overall survival (OS) and relapse free survival (RFS) than their counterparts. In conclusion, DDX3 may play an oncogenic role to promote tumor growth and invasion in colon cancer cells via the beta-catenin/ZEB1 axis due to increasing KRAS transcription. We therefore suggest that AKT or beta-catenin may potentially act as a therapeutic target to improve tumor regression and outcomes in colorectal cancer patients who harbored high DDX3 tumors. PMID- 27007151 TI - Multilevel induction of apoptosis by microtubule-interfering inhibitors 4beta-S aromatic heterocyclic podophyllum derivatives causing multi-fold mitochondrial depolarization and PKA signaling pathways in HeLa cells. AB - Herein is a first effort to study effect of carbon-sulfur (C-S) and carbon nitrogen (C-N) bonds modification on the antitumor activity of the podophyllum derivatives in HeLa cells. Compared with the derivative modified by the C-N bond, the C-S bond modification exhibited superior antitumor activity by further causing significant mitochondria depolarization from three signaling pathway. First, a large number of microtubules were depolymerized by 4beta-S-heterocyclic substituted podophyllum derivatives. The increasing free tubulin bond with voltage-dependent anion-selective channel (VDAC). Second, cAMP-dependent protein kinase A (PKA) was activated by 4beta-S-heterocyclic substituted podophyllum derivatives. And then the activated PKA further caused significantly mitochondria depolarization. Third, the activated PKA also activated c-Jun N-terminal kinase (JNK) and further deceased MMP by improving the level of reactive oxygen species. Understanding the molecular events that contribute to drug-induced tumors apoptosis should provide a paradigm for a more rational approach to antitumor drug design. PMID- 27007152 TI - Applying of pretreatment extent of disease system in patients with hepatocellular carcinoma after curative partial hepatectomy. AB - The Pretreatment Extent of Disease System (PRETEXT) was designed for childhood liver tumors. The aim of this study was to confirm the prognostic value of the PRETEXT staging system compared with the currently and commonly used staging systems of hepatocellular carcinoma (HCC) after applying PRETEXT system in patients with HCC who underwent curative partial hepatectomy.Clinical data of consecutive patients who underwent curative partial hepatectomy were collected between February 1st, 2005 to December 30th, 2012 as the primary and internal validation cohort. Similar patients from a western hospital formed an external validation cohort. The predictive accuracy of the PRETEXT system compared with the currently used staging systems was measured by the area under the curve (AUC) on receiver operating characteristic (ROC) curve analysis. Of the 507 patients in the primary cohort, the overall median survival was 52.3 months, and the 1-year, 3-year, and 5-year overall survival rates were 83.0%, 56.8%, and 40.2%, respectively. The multivariate analysis of Cox proportional hazard regression identified INR (p=0.001), microvascular invasion (p=0.042), maximum tumor size (p=0.002) and PRETEXT staging system were independently predictors of overall survival. In the primary cohort, the AUC of the PRETEXT system was 0.702 (95% CI, 0.656 to 0.747), which was higher than the other conventional staging systems for predicting OS of HCC (P<0.01). These findings were confirmed with the internal and external validation cohorts.This study showed that the PRETEXT was a good prognostic staging system for HCC. It performed better than the conventional and commonly used staging systems in predicting survival of patients with HCC after curative partial hepatectomy. PMID- 27007153 TI - A novel prognostic score model incorporating CDGSH iron sulfur domain2 (CISD2) predicts risk of disease progression in laryngeal squamous cell carcinoma. AB - BACKGROUND: The role of CDGSH iron sulfur domain 2 (CISD2) in laryngeal squamous cell carcinoma (LSCC) remains unclear. RESULTS: CISD2 were up-regulated in LSCC tissues compared with adjacent noncancerous tissues both at mRNA and protein levels. CISD2 was significantly correlated with T stage, lymph node metastasis, clinical stage and disease progression. A prognostic model (C-N model) for PFS was subsequently constructed based on independent prognostic factors including CISD2 and N classification. This model significantly divided LSCC patients into three risk subgroups and was more accurate than the prediction efficacy of TNM classification in the training cohort (C-index, 0.710 vs 0.602, P = 0.027) and validation cohort (C-index, 0.719 vs 0.578, P = 0.014). METHODS: Real-time PCR and Western blotting were employed to examine the expression of CISD2 in eight fresh paired LSCC samples. Immunohistochemistry was performed to assess CISD2 expression in 490 paraffin-embedded archived LSCC samples. A prognostic model for progression-free survival (PFS) was built using independent factors. The concordance index (C-Index) was used to evaluate the prognostic ability of the model. CONCLUSIONS: CISD2 was up-regulated in LSCC. The novel C-N model, which includes CISD2 levels and N classification, is more accurate than conventional TNM classification for predicting PFS in LSCC. PMID- 27007154 TI - Multiple myeloma cancer stem cells. AB - Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contributes to disease relapse, but the mechanisms of drug resistance have not been fully understood. The major signaling pathways involved in the regulation of self-renewal and differentiation of MMSCs include Hedgehog (Hh), Wingless (Wnt), Notch and PI3K/Akt/mTOR. However, the precise role of these signaling pathways needs to be clarified. It has been reported that the microRNA profile of MMSCs is remarkably different than that of non-MMSCs. Therefore, the search for targeting MMSCs has also been focused on microRNAs. Complex and mutual interactions between the MMSC and the surrounding bone marrow (BM) microenvironment sustain self-renewal and survival of MMSC. However, the required molecules for the interaction of the MMSC and the surrounding BM microenvironment need to be further identified. In this review, we summarize the current state of knowledge of MMSCs regarding their phenotype, mechanisms of drug resistance, signaling pathways that regulate MMSCs self renewal and differentiation, abnormal microRNAs expression, and their interactions with the BM microenvironment. PMID- 27007155 TI - Hallmarks of glycosylation in cancer. AB - Aberrant glycosylation plays a fundamental role in key pathological steps of tumour development and progression. Glycans have roles in cancer cell signalling, tumour cell dissociation and invasion, cell-matrix interactions, angiogenesis, metastasis and immune modulation. Aberrant glycosylation is often cited as a 'hallmark of cancer' but is notably absent from both the original hallmarks of cancer and from the next generation of emerging hallmarks. This review discusses how glycosylation is clearly an enabling characteristic that is causally associated with the acquisition of all the hallmark capabilities. Rather than aberrant glycosylation being itself a hallmark of cancer, another perspective is that glycans play a role in every recognised cancer hallmark. PMID- 27007156 TI - The effects of graded levels of calorie restriction: V. Impact of short term calorie and protein restriction on physical activity in the C57BL/6 mouse. AB - Calorie restriction (CR) delays the onset of age-related disease and extends lifespan in a number of species. When faced with reduced energy supply animals need to lower energy demands, which may be achieved in part by reducing physical activity (PA). We monitored changes in PA using implanted transmitters in male C57BL/6 mice in response to graded levels of CR (10 to 40%) or matched levels of graded protein restriction (PR) for 3 months. Mice were fed at lights out and ad libitum controls were limited to dark-phase feeding (12AL) or 24hr/day. Total daily PA declined in a non-linear manner over the first 30 days of CR or PR, remaining stable thereafter. Total daily PA was not related to the level of CR or PR. Total daily PA over the last 20 days of restriction was related to circulating leptin, insulin, tumor necrosis factor-alpha (TNF- alpha) and insulin like growth factor (IGF)-1 levels, measured after 3 months. Mice under restriction showed a high level of activity in the 2hrs before feeding (food anticipatory activity: FAA). FAA followed a complex pattern, peaking around day 20, falling on ~day 37 then increasing again. FAA was also positively related to the level of restriction and inversely to leptin, insulin, TNF-alpha and IGF-1. Non-FAA, in contrast, declined over the period of restriction, generally more so in mice under greater restriction, thereby offsetting to some extent the increase in FAA. Mice under PR displayed no changes in PA over time or in comparison to 12AL, and showed no increase in FAA. PMID- 27007157 TI - Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus. AB - While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor alpha (ERalpha) in the female reproductive tracts. Using knock-in mouse models expressing ERalpha mutants, we determined that the DNA-binding domain (DBD) and AF2 domain of ERalpha were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERalpha AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERalpha DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERalpha. Epithelial ERalpha was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus. PMID- 27007159 TI - Genetic overlap between type 2 diabetes and major depressive disorder identified by bioinformatics analysis. AB - Our study investigated the shared genetic etiology underlying type 2 diabetes (T2D) and major depressive disorder (MDD) by analyzing large-scale genome wide association studies statistics. A total of 496 shared SNPs associated with both T2D and MDD were identified at p-value <= 1.0E-07. Functional enrichment analysis showed that the enriched pathways pertained to immune responses (Fc gamma R mediated phagocytosis, T cell and B cell receptors signaling), cell signaling (MAPK, Wnt signaling), lipid metabolism, and cancer associated pathways. The findings will have potential implications for future interventional studies of the two diseases. PMID- 27007158 TI - FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype. AB - Inflammatory monocyte and tissue macrophages influence the initiation, progression, and resolution of type 2 immune responses, and alveolar macrophages are the most prevalent immune-effector cells in the lung. While we were characterizing the M1- or M2-like macrophages in type 2 allergic inflammation, we discovered that FoxO1 is highly expressed in alternatively activated macrophages. Although several studies have been focused on the fundamental role of FoxOs in hematopoietic and immune cells, the exact role that FoxO1 plays in allergic asthmatic inflammation in activated macrophages has not been investigated. Growing evidences indicate that FoxO1 acts as an upstream regulator of IRF4 and could have a role in a specific inflammatory phenotype of macrophages. Therefore, we hypothesized that IRF4 expression regulated by FoxO1 in alveolar macrophages is required for established type 2 immune mediates allergic lung inflammation. Our data indicate that targeted deletion of FoxO1 using FoxO1-selective inhibitor AS1842856 and genetic ablation of FoxO1 in macrophages significantly decreases IRF4 and various M2 macrophage-associated genes, suggesting a mechanism that involves FoxO1-IRF4 signaling in alveolar macrophages that works to polarize macrophages toward established type 2 immune responses. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, macrophage specific FoxO1 overexpression is associated with an accentuation of asthmatic lung inflammation, whereas pharmacologic inhibition of FoxO1 by AS1842856 attenuates the development of asthmatic lung inflammation. Thus, our study identifies a role for FoxO1-IRF4 signaling in the development of alternatively activated alveolar macrophages that contribute to type 2 allergic airway inflammation. PMID- 27007160 TI - CHIP: A new modulator of human malignant disorders. AB - Carboxyl terminus of Hsc70-interacting protein (CHIP) is known as a chaperone associated E3 for a variety of protein substrates. It acts as a link between molecular chaperones and ubiquitin-proteasome system. Involved in the process of protein clearance, CHIP plays a critical role in maintaining protein homeostasis in diverse conditions. Here, we provide a comprehensive review of our current understanding of CHIP and summarize recent advances in CHIP biology, with a focus on CHIP in the setting of malignancies. PMID- 27007161 TI - Phenylethanolamine N-methyltransferase downregulation is associated with malignant pheochromocytoma/paraganglioma. AB - Malignant pheochromocytoma/paraganglioma (PCC/PGL) is defined by the presence of metastases at non-chromaffin sites, which makes it difficult to prospectively diagnose malignancy. Here, we performed array CGH (aCGH) and paired gene expression profiling of fresh, frozen PCC/PGL samples (n = 12), including three malignant tumors, to identify genes that distinguish benign from malignant tumors. Most PCC/PGL cases showed few copy number aberrations, regardless of malignancy status, but mRNA analysis revealed that 390 genes were differentially expressed in benign and malignant tumors. Expression of the enzyme, phenylethanolamine N-methyltransferase (PNMT), which catalyzes the methylation of norepinephrine to epinephrine, was significantly lower in malignant PCC/PGL as compared to benign samples. In 62 additional samples, we confirmed that PNMT mRNA and protein levels were decreased in malignant PCC/PGL using quantitative real time polymerase chain reaction and immunohistochemistry. The present study demonstrates that PNMT downregulation correlates with malignancy in PCC/PGL and identifies PNMT as one of the most differentially expressed genes between malignant and benign tumors. PMID- 27007162 TI - Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to promote invasive and metastatic potentials of human gastric cancer. AB - Runt-related transcription factor 2 (RUNX2) is a regulator of embryogenesis and development, but has also been implicated in the progression of certain human cancer. This study aimed to elucidate the role of RUNX2 in the invasive and metastatic potentials of human gastric cancer (GC) and the underlying mechanisms. We found that the levels of RUNX2 expression in gastric cancer tissues were correlated with the differentiation degrees, invasion depth and lymph node metastasis. COX regression analysis indicated that RUNX2 was an independent prognostic indicator for GC patients. RUNX2 significantly increased the migration and invasion ability of GC cells in vitro and enhanced the invasion and metastatic potential of GC cells in an orthotopic GC model of nude mice. Mechanistically, RUNX2 directly bound to the promoter region of the gene coding for the chemokine receptor CXCR4 to enhance its transcription. CXCR4 knockdown or treatment with AMD3100, a CXCR4 inhibitor, attenuated RUNX2-promoted invasion and metastasis. These results demonstrate that RUNX2 promotes the invasion and metastasis of human GC by transcriptionally up-regulating the chemokine receptor CXCR4. Therefore, the RUNX2-CXCR4 axis is a potential therapeutic target for GC. PMID- 27007164 TI - Toward A Scalable, Patient-Centered Community Health Worker Model: Adapting the IMPaCT Intervention for Use in the Outpatient Setting. AB - Community health worker (CHW) programs are an increasingly popular strategy for patient-centered care. Many health care organizations are building CHW programs through trial and error, rather than implementing or adapting evidence-based interventions. This study used a qualitative design-mapping process to adapt an evidence-based CHW intervention, originally developed and tested in the hospital setting, for use among outpatients with multiple chronic conditions. The study involved qualitative in-depth, semi-structured interviews with chronically ill, uninsured, or Medicaid outpatients from low-income zip codes (n = 21) and their primary care practice staff (n = 30). Three key themes informed adaptation of the original intervention for outpatients with multiple conditions. First, outpatients were overwhelmed by their multiple conditions and wished they could focus on 1 at a time. Thus, the first major revision was to design a low-literacy decision aid that patients and providers could use to select a condition to focus on during the intervention. Second, motivation for health behavior change was a more prominent theme than in the original intervention. It was decided that in addition to providing tailored social support as in the original intervention, CHWs would help patients track progress toward their chronic disease management goals to motivate health behavior change. Third, patients were already connected to primary care; yet they still needed additional support to navigate their clinic once the intervention ended. The intervention was revised to include a weekly clinic-based support group. Structured adaptation using qualitative design mapping may allow for rapid adaptation and scale-up of evidence-based CHW interventions across new settings and populations. PMID- 27007165 TI - African Americans and Hospice Care: A Culture-Centered Exploration of Enrollment Disparities. AB - Over the past decade, scholars and practitioners have called for efforts to reduce disparities in the cost and quality of end-of-life care; a key contributor to these disparities is the underuse of hospice care by African American patients. While previous studies have often relied on interviewing minority individuals who may or may not have been terminally ill and of whom few were using hospice care services, this essay draws upon the culture-centered approach to report the findings of a grounded theory analysis of 39 interviews with 26 African American hospice patients (n = 10) and lay caregivers (n = 16). Participants identified several barriers to hospice enrollment and reported how they were able to overcome these barriers by reframing/prioritizing cultural values and practices, creating alternative goals for hospice care, and relying on information obtained outside the formal health system. These findings have implications for understanding hospice experiences, promoting hospice access, and improving end-of-life care. PMID- 27007163 TI - Oncogenic protein SALL4 and ZNF217 as prognostic indicators in solid cancers: a meta-analysis of individual studies. AB - BACKGROUND: SALL4 and ZNF217 have been widely acknowledged as pivotal effectors stimulating embryonic immortalization as well as oncogenicity. Nevertheless, their prognostic worthiness towards solid tumors remains obscure. Hence we performed this comprehensive meta-analysis aiming to unveil the survival significance of both aberrantly expressed proteins. RESULTS: Overall we included 22 eligible entries comprising of 3093 participants. Over-expression of SALL4 and ZNF217 were negatively correlated with clinical prognosis of 3-year, 5-year, 10 year and disease-free survival in solid malignancies, irrespective of cancer types, source regions, mean-age and sex predominance. Results of sensitivity analysis additionally verified the stability of the pooled outcomes. No publication bias was observed on the basis of Egger's test and Begg's test. METHODS: Studies were eventually included via database searching and rigorous eligibility appraisal. Data extraction and methodological assessment were implemented under a standard manner. Review Manager 5.3 and STATA 12.0 were utilized as statistical platforms following the recommendations by Cochrane Collaboration protocols. CONCLUSIONS: Aberrant amplification of SALL4 and ZNF217 serve as unfavorable predictors of survival expectancy among cancer sufferers, revealing great potential as targeted spots in future therapeutics. PMID- 27007166 TI - Predicting Retweeting Behavior on Breast Cancer Social Networks: Network and Content Characteristics. AB - This study explored how social media, especially Twitter, serves as a viable place for communicating about cancer. Using a 2-step analytic method that combined social network analysis and computer-aided content analysis, this study investigated (a) how different types of network structures explain retweeting behavior and (b) which types of tweets are retweeted and why some messages generate more interaction among users. The analysis revealed that messages written by users who had a higher number of followers, a higher level of personal influence over the interaction, and closer relationships and similarities with other users were retweeted. In addition, a tweet with a higher level of positive emotion was more likely to be retweeted, whereas a tweet with a higher level of tentative words was less likely to be retweeted. These findings imply that Twitter can be an effective tool for the dissemination of health information. Theoretical and practical implications for psychosocial interventions for people with health concerns are discussed. PMID- 27007167 TI - Isolation and Characterization of Stenotrophomonas maltophilia Isolates from a Brazilian Hospital. AB - Stenotrophomonas maltophilia is an emerging nosocomial pathogen responsible for several infections in immunocompromised patients. To characterize the antimicrobial resistance and virulence potential of this microorganism in a Brazilian hospital, a total of 936 samples were collected from a nosocomial environment and medical devices, and 100 isolates from clinical specimens were obtained in the same hospital. S. maltophilia was found in 3% of the samples collected, especially in bed rails from hospital rooms. The smf-1 gene was detected in 23% and 42% of the clinical and hospital environment isolates, respectively, and almost all (96.8%) isolates that harbored smf-1 were able to form biofilm. All isolates were susceptible to minocycline and chloramphenicol, and the majority of isolates were susceptible to levofloxacin. High resistance to ceftazidime was detected in both groups of isolates. Resistance to trimethoprim sulfamethoxazole (TMP/SMX) was found in 14.8% of the isolates. All TMP/SMX resistant isolates presented class 1 integron and sul1 gene, and 47.4% of them also harbored the sul2 gene, which was inserted into a 7.3 kb plasmid. Genetic relatedness among the isolates was evaluated by enterobacterial repetitive intergenic consensus-PCR, and eight genetic patterns were identified. One pattern comprised 54.7% of isolates and was spread among clinical and environmental (furniture and medical devices) sources. The presence of S. maltophilia in the hospital environment indicates that it can act as a reservoir of this microorganism. In addition, hospital isolates resistant to TMP/SMX showed that the genetic determinants were present in mobile elements, which can constitute great concern, as it may indicate a tendency to spread. PMID- 27007168 TI - A comparison of visual search strategies of elite and non-elite tennis players through cluster analysis. AB - Considerable research has documented that successful performance in interceptive tasks (such as return of serve in tennis) is based on the performers' capability to capture appropriate anticipatory information prior to the flight path of the approaching object. Athletes of higher skill tend to fixate on different locations in the playing environment prior to initiation of a skill than their lesser skilled counterparts. The purpose of this study was to examine visual search behaviour strategies of elite (world ranked) tennis players and non-ranked competitive tennis players (n = 43) utilising cluster analysis. The results of hierarchical (Ward's method) and nonhierarchical (k means) cluster analyses revealed three different clusters. The clustering method distinguished visual behaviour of high, middle-and low-ranked players. Specifically, high-ranked players demonstrated longer mean fixation duration and lower variation of visual search than middle-and low-ranked players. In conclusion, the results demonstrated that cluster analysis is a useful tool for detecting and analysing the areas of interest for use in experimental analysis of expertise and to distinguish visual search variables among participants'. PMID- 27007170 TI - The Impact of Hazardous Alcohol Use on Behavioral Healthcare Utilization Among National Guard Service Members. AB - BACKGROUND: Prior research suggests that both posttraumatic stress disorder (PTSD) and alcohol abuse affect behavioral healthcare utilization among combat exposed military populations. However, their interactive effect is not well documented, especially after experiencing psychological trauma. OBJECTIVE: This study examined the role of hazardous alcohol use (i.e. repeated patterns of drinking which lead to harmful consequences) on behavioral healthcare utilization among service members stratified by past-year combat exposure. METHOD: This study utilized a sample of National Guard service members who participated in an in depth survey 2-4 months after returning from Operation Enduring Freedom, Operation Iraqi Freedom, or Operation New Dawn deployments (2011-2013) (n = 467). We examine the marginal effect (the change in the probability) of hazardous alcohol use on utilization while controlling for trauma exposure, PTSD and other potential covariates. RESULTS: In the unadjusted logistic model, hazardous alcohol use reduced the probability of behavioral healthcare utilization by 77% among service members who had been exposed to combat within the past year. In the adjusted model, which controlled for socio-demographics (age, gender, and race), health status (PTSD symptoms, depression and physical health), and measures of stigma (perception of services as embarrassing or harmful to one's career or social networks), hazardous alcohol use further reduced the utilization probability by 302%. CONCLUSION/IMPORTANCE: Although these findings require replication, they appear to demonstrate that when combat-exposed service members engaged in hazardous alcohol use at postdeployment, they were much less likely to utilize behavioral healthcare to manage their posttraumatic stress symptoms during this period. PMID- 27007169 TI - Reports of Perceived Adverse Events of Stimulant Medication on Cognition, Motivation, and Mood: Qualitative Investigation and the Generation of Items for the Medication and Cognition Rating Scale. AB - OBJECTIVE: There is no questionnaire to specifically monitor perceived adverse events of methylphenidate (MPH) on cognition, motivation, and mood. The current study therefore had two goals. First, to harvest accounts of such putative events from transcripts of interviews in samples enriched for such potential experiences. Second, to use the derived data to generate items for a new questionnaire that can be used for monitoring such events in medication trials or routine clinical care. METHODS: Following a literature search aimed at identifying associations between MPH and cognition and/or motivation, a qualitative semistructured interview was designed to focus specifically on the domains of cognition (i.e., reasoning, depth/breadth of thinking, intellectual capacity, and creativity) and motivation (i.e., drive, effort, and attitudes toward rewards/incentives). Interviews were conducted with 45 participants drawn from the following four groups: (a) clinicians, child and adolescent psychiatrists, and pediatricians specializing in attention-deficit/hyperactivity disorder (ADHD) (n = 15); (2) teachers, with experience of teaching at least 10 medicated children with ADHD (n = 10); (3) parents of children with ADHD (n = 8) treated with MPH; and (4) adolescents/adults with ADHD (n = 12). Purposeful sampling was used to selectively recruit ADHD participants whose histories suggested a degree of vulnerability to MPH adverse events. Data were analyzed using a deductive approach to content analysis. RESULTS: While we probed purposefully for cognitive and motivational adverse events, a third domain, related to mood, emerged from the reports. Therefore, three domains, each with a number of subdomains, were identified from the interview accounts: (i) Cognition (six subdomains; attention/concentration, changes in thinking, reduced creativity, sensory overload, memory, slower processing speed); (ii) motivation (four subdomains; loss of intrinsic motivation for goal-directed activities, external locus of control, lack of effort/engagement in daily tasks, increased focus on incentives); and (iii) mood (three subdomains; dampening of spontaneity/flat affect, mood dysregulation, increased anxiety/edginess). On the basis of these reports, 34 items were specified and incorporated into a prototype questionnaire, which was piloted and refined on the basis of field-testing. CONCLUSIONS: Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects). PMID- 27007172 TI - Geometrical Effects on the Magnetic Properties of Nanoparticles. AB - Elucidating the connection between shape and properties is a challenging but essential task for a rational design of nanoparticles at the atomic level. As a paradigmatic example we investigate how geometry can influence the magnetic properties of nanoparticles, focusing in particular on platinum clusters of 1-2 nm in size. Through first-principle calculations, we have found that the total magnetization depends strongly on the local atomic arrangements. This is due to a contraction of the nearest neighbor distance together with an elongation of the second nearest neighbor distance, resulting in an interatomic partial charge transfer from the atoms lying on the subsurface layer (donors) toward the vertexes (acceptors). PMID- 27007178 TI - The Efficacy of Intraoperative Single Dose Methylprednisolone on Recurrent Laryngeal Nerve Function After Thyroidectomy. AB - OBJECTIVE: Primary endpoint is to determine whether intraoperative steroid affect post-thyroidectomy recurrent laryngeal palsy or not Background: Recurrent laryngeal nerve (RLN) palsy is an important complication of thyroid surgery. Injuries can either be permanent or temporary. Prevention or shortening the recovery period of temporary palsies is an area of interest. Some surgeons prefer to use corticosteroids for this purpose as is used for facial nerve palsies although there are conflicting data in the literature. We aimed to investigate the efficacy of perioperative single dose methylprednisolone on RLN function. METHOD: 438 nerves under risk in 237 surgeries are investigated in two groups. Group 1, patients are administered a single intraoperative dose of methylprednisolone (1mg/kg) intravenously for 220 nerves under risk. 218 nerves under risk in Group 2 were operated and followed without methylprednisolone. The demographic data of the patients, operation time, the final pathology reports, incidence of RLNP and recovery time are documented and compared. RESULTS: No statistically significant difference was determined in terms of age, sex distribution, number of nerves under risk and the operation time between groups. There were 3 unilateral RLNP in each group and the mean recovery time for Group 1 and 2 palsies were 20.4 and 19.8 days respectively, without statistical significance. CONCLUSION: The presented data indicates that a single intraoperative dose of steroid does not seem to effect the rate and recovery period of RLNP in thyroid surgery. PMID- 27007171 TI - Pulmonary Abnormalities in Young, Light-Use Waterpipe (Hookah) Smokers. AB - RATIONALE: Waterpipes, also called hookahs, are currently used by millions of people worldwide. Despite the increasing use of waterpipe smoking, there is limited data on the health effects of waterpipe smoking and there are no federal regulations regarding its use. OBJECTIVES: To assess the effects of waterpipe smoking on the human lung using clinical and biological parameters in young, light-use waterpipe smokers. METHODS: We assessed young, light-use, waterpipe only smokers in comparison with lifelong nonsmokers using clinical parameters of cough and sputum scores, lung function, and chest high-resolution computed tomography as well as biological parameters of lung epithelial lining fluid metabolome, small airway epithelial (SAE) cell differential and transcriptome, alveolar macrophage transcriptome, and plasma apoptotic endothelial cell microparticles. MEASUREMENTS AND MAIN RESULTS: Compared with nonsmokers, waterpipe smokers had more cough and sputum as well as a lower lung diffusing capacity, abnormal epithelial lining fluid metabolome profile, increased proportions of SAE secretory and intermediate cells, reduced proportions of SAE ciliated and basal cells, markedly abnormal SAE and alveolar macrophage transcriptomes, and elevated levels of apoptotic endothelial cell microparticles. CONCLUSIONS: Young, light-use, waterpipe-only smokers have a variety of abnormalities in multiple lung-related biological and clinical parameters, suggesting that even limited waterpipe use has broad consequences on human lung biology and health. We suggest that large epidemiological studies should be initiated to investigate the harmful effects of waterpipe smoking. PMID- 27007173 TI - Evaluation of retinal nerve fiber layer thickness and choroidal thickness in pseudoexfoliative glaucoma and pseudoexfoliative syndrome. AB - OBJECTIVES: To compare retinal nerve fiber layer thickness (RNFLT) and choroidal thickness (ChT) measurements in eyes with pseudoexfoliative (PEX) glaucoma, PEX syndrome and healthy control eyes. METHODS: Eighteen patients with PEX glaucoma in one eye and PEX syndrome in the fellow eye were included. The right eyes of thirty-nine age- and sex-matched healthy subjects were included as control group. All participants underwent a detailed biomicroscopic and funduscopic examination. RNFLT and ChT measurements were performed with a commercially available spectral domain optical coherence tomography (SD-OCT). ChT measurements were performed by using enhanced depth imaging (EDI) mode. Patients with PEX underwent diurnal IOP measurements with 4-hour intervals before inclusion in the study. RNFLT results included the average measurement and 6 quadrants (temporal, inferotemporal, inferonasal, nasal, superonasal and supero-temporal). ChT measurements were performed in the subfoveal region and around the fovea (500um and 1500 um nasal and temporal to the fovea), as well as around the optic disc (average peripapillary and eight quadrants in the peripapillary region (temporal, inferotemporal, inferior, inferonasal, nasal, superonasal, superior, supero temporal)). RESULTS: RNFLT in all quadrants and average thickness were significantly lower in PEX glaucoma eyes compared to PEX syndrome eyes and healthy control eyes (p<0.001 for both). RNFLT comparisons between PEX syndrome and healthy control eyes did not show a significant difference (p>0.05) except the inferotemporal quadrant. ChT measurements were similar between groups (p>0.05). CONCLUSIONS: Thinning of the RNFL in association with unchanged ChT may mean that the presence of PEX material is a much more significant risk factor than choroidal changes in the progression of PEX syndrome to PEX glaucoma. PMID- 27007179 TI - Construction of Compact Polyelectrolyte Multilayers Inspired by Marine Mussel: Effects of Salt Concentration and pH As Observed by QCM-D and AFM. AB - Biomimetic multilayers based on layer-by-layer (LbL) assembly were prepared as functional films with compact structure by incorporating the mussel-inspired catechol cross-linking. Dopamine-modified poly(acrylic acid) (PAADopa) was synthesized as a polyanion to offer electrostatic interaction with the prelayer polyethylenimine (PEI) and consecutively cross-linked by zinc to generate compact multilayers with tunable physicochemical properties. In situ layer-by-layer growth and cross-linking were monitored by a quartz crystal microbalance with dissipation (QCM-D) to reveal the kinetics of the process and the influence of Dopa chemistry. Addition of Dopa enhanced the mass adsorption and led to the formation of a more compact structure. An increase of ionic strength induced an increase in mass adsorption in the Dopa-cross-linked multilayers. This is a universal approach for coating of various surfaces such as Au, SiO2, Ti, and Al2O3. Roughness observed by AFM in both wet and dry conditions was compared to confirm the compact morphology of Dopa-cross-linked multilayers. Because of the pH sensitivity of Dopa moiety, metal-chelated Dopa groups can be turned into softer structure at higher pH as revealed by reduction of Young's modulus determined by MFP-3D AFM. A deeper insight into the growth and mechanical properties of Dopa-cross-linked polyelectrolyte multilayers was addressed in the present study. This allows a better control of these systems for bioapplications. PMID- 27007180 TI - A simple method of evaluating margin-growing accuracy in image-guided radiation therapy. AB - OBJECTIVE: In order to not add extra uncertainty to radiotherapy planning process, accurate margin algorithm is necessary, therefore we propose a centre shift method to estimate its accuracy. METHODS: A series of spherical phantoms are used with different CT slice separations (SSs) and pixel sizes (PSs). They are grown by different margins, and displaced geometric centres provide a window on accuracy. Volume difference between pre- and post-expansion is also calculated to double-check the accuracy. RESULTS: The measured margin nearly varies as multiples of PS in the transaxial plane; in the superior-inferior direction, it is approximately equal to SS when the ideal margin is smaller than SS. A sphere's volume of <1 cm(3) is underestimated by 3-70% for all PSs, and 2-100% for SS of <=5 mm but overestimated up to 112% for >5 mm. For volumes of >1 cm(3), relative volume error decreases, and it is nearly zero for >100 cm(3). The dependence of margin accuracy on SS and PS is largely eliminated by volume difference method. CONCLUSION: We have proposed a simple method to estimate margin-growing accuracy and suggested corrective action to minimize the variation. ADVANCES IN KNOWLEDGE: One big difference from the previous results is that SS and PS both influence the accuracy of margin growth and volume calculation in Eclipse(TM) treatment planning system (Varian Medical System, Palo Alto, CA). PMID- 27007181 TI - Could Caffeic Acid Phenethyl Ester Expand the Antitumor Effect of Tamoxifen in Breast Carcinoma? AB - Despite tamoxifen (TAM) is beneficial in treating a significant proportion of patients with breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis, with a plethora of important biological actions including anticancer activity. This study aimed to explore the cytotoxicity, the type of drugs interaction as well as the apoptotic and autophagic pathways of the combined treatment of TAM and CAPE in MCF-7 cells. Their antitumor activity and effect on survival of mice bearing Ehrlich tumor were also analyzed. The results showed synergistic cytotoxic effects, manifested by significant activation of apoptotic machinery, along with downregulation of protein levels of Bcl-2 and beclin-1, upon using the combination regimen. However, the ratio between microtubule-associated protein light chain 3-II and -I was not altered. Moreover, a decrease in vascular endothelial growth factor level was detected. Similarly, TAM + CAPE increased the life span of tumor-bearing animals and caused a marked regression in their tumor size and weight compared with those treated with either TAM or CAPE alone. In conclusion, CAPE relatively improved the anticancer activity of TAM in both in vitro and in vivo models via its apoptotic and angiostatic potentials. PMID- 27007182 TI - The Study of Reactive Intermediates in Condensed Phases. AB - Novel experimental techniques and computational methods have provided new insight into the behavior of reactive intermediates in solution. The results of these studies show that some of the earlier ideas about how reactive intermediates ought to behave in solution were incomplete or even incorrect. This Perspective summarizes the new experimental and computational methods and draws attention to the shortcomings that their application has brought to light in previous models. Key areas needing further research are highlighted. PMID- 27007183 TI - A cross-sectional evaluation examining the use of the Achilles tendinopathy toolkit by physiotherapists in British Columbia, Canada. AB - PURPOSE: To evaluate the awareness and use of the Achilles tendinopathy toolkit (ATT), a knowledge translation (KT) strategy supporting evidence-informed management of midportion Achilles Tendinopathy (AT), by British Columbian physiotherapists (PTs). Secondarily, to assess PTs strategies for AT management by examining the association between exploring the ATT and following best practice in clinical care as recommended by the ATT. METHODS: Members of the Physiotherapy Association of British Columbia (BC) completed an online cross sectional survey collecting information on demographics; awareness and exposure; perceptions, usability and applicability to clinical practice; knowledge; and attitudes. A clinical vignette assessed if respondents adhered to recommendations made by the ATT. Multi-variable logistic regression examined the association between exploring the ATT and following its recommendations. RESULTS: Of 238 participants, 81% (n = 154) were aware of the ATT and of those 53% (n = 81) explored its contents. Time was the most frequent barrier. Bi-variable analyses showed those who explored the ATT had over double the odds of following the best practice (odds ratio = OR = 2.8; 95% confidence interval = 95% CI = 1.3-6.0). This did not remain significant in the final adjusted model (OR = 2.2; 95% CI = 0.9-5.4). CONCLUSIONS: Evaluation of KT strategies is critical. This study revealed high awareness and moderate use of the ATT. Future work should consider the impact of toolkits on patient outcomes. Implications for Rehabilitation A toolkit is a novel knowledge translation (KT) strategy designed to provide accessibleevidence-informed resources to facilitate best practice by clinicians. The evaluation of the Achilles tendinopathy toolkit (ATT) revealed favourable findingsregarding the impact of this KT strategy on the knowledge and attitudes of British Columbia(BC) PTs and the possibility of a positive impact on best practice in clinical care. This research suggests toolkits are a feasible and meaningful KT strategy to provide clinicianswith valuable synthesized resources that have the potential to benefit patient outcomes. PMID- 27007184 TI - Self-Forming 3D Core-Shell Ceramic Nanostructures for Halogen-Free Flame Retardant Materials. AB - The synthesis of aluminum phosphates-based composites has been widely studied during the past decade because of the promising industrial application of these materials. Here we show a simple one-pot heterogeneous precipitation approach to fabricate a sepiolite-phosphate (SepP) composite with adequate control of the size and dispersion of the phosphate nanoparticles. This coupling between aluminum phosphate and sepiolite nanofibers results in the development of a novel three-dimensional rigid supported phosphate structure, which is generated during the thermal treatment. According to our results, this phenomenon can be explained by a migration-coalescence mechanism of phosphate nanoparticles over the sepiolite support, assisted by a liquid phase. It is worth pointing out that this stimulant behavior observed here could have potential technological applications such as halogen-free flame retardant materials. PMID- 27007185 TI - Gamma Secretase Modulators: New Alzheimer's Drugs on the Horizon? AB - The rapidly aging population desperately requires new therapies for Alzheimer's disease. Despite years of pharmaceutical research, limited clinical success has been realized, with several failed disease modification therapies in recent years. On the basis of compelling genetic evidence, the pharmaceutical industry has put a large emphasis on brain beta amyloid (Abeta) either through its removal via antibodies or by targeting the proteases responsible for its production. In this Perspective, we focus on the development of small molecules that improve the activity of one such protease, gamma secretase, through an allosteric binding site to preferentially increase the concentration of the shorter non amyloidogenic Abeta species. After a few early failures due to poor drug-like properties, the industry is now on the cusp of delivering gamma secretase modulators for clinical proof-of-mechanism studies that combine potency and efficacy with improved drug-like properties such as lower cLogP, high central nervous system multiparameter optimization scores, and high sp(3) character. PMID- 27007186 TI - Effect of Vitamin E and Omega-3 Fatty Acids on Protecting Ambient PM2.5-Induced Inflammatory Response and Oxidative Stress in Vascular Endothelial Cells. AB - Although the mechanisms linking cardiopulmonary diseases to ambient fine particles (PM2.5) are still unclear, inflammation and oxidative stress play important roles in PM2.5-induced injury. It is well known that inflammation and oxidative stress could be restricted by vitamin E (Ve) or omega-3 fatty acids (Omega-3 FA) consumption. This study investigated the effects of Ve and Omega-3 FA on PM2.5-induced inflammation and oxidative stress in vascular endothelial cells. The underlying mechanisms linking PM2.5 to vascular endothelial injury were also explored. Human umbilical vein endothelial cells (HUVECs) were treated with 50 MUg/mL PM2.5 in the presence or absence of different concentrations of Ve and Omega-3 FA. The inflammatory cytokines and oxidative stress markers were determined. The results showed that Ve induced a significant decrease in PM2.5 induced inflammation and oxidative stress. Malondialdehyde (MDA) in supernatant and reactive oxygen species (ROS) in cytoplasm decreased by Ve, while the superoxide dismutase (SOD) activity elevated. The inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) also reduced by Ve. Moreover, Omega-3 FA played the same role on decreasing the inflammation and oxidative stress. IL-6 and TNF-alpha expressions were significantly lower in combined Ve with Omega-3 FA than treatment with Ve or Omega-3 FA alone. The Ve and Omega-3 FA intervention might abolish the PM2.5-induced oxidative stress and inflammation in vascular endothelial cells. There might be an additive effect of these two nutrients in mediating the PM2.5-induced injury in vascular endothelial cells. The results suggested that inflammation and oxidative stress might be parts of the mechanisms linking PM2.5 to vascular endothelial injury. PMID- 27007187 TI - Spatial Differences and Costs of Emissions at U.S. Airport Hubs. AB - As local governments plan to expand airport infrastructure and build air service, monetized estimates of damages from air pollution are important for balancing environmental impacts. While it is well-known that aircraft emissions near airports directly affect nearby populations, it is less clear how the airport specific aircraft operations and impacts result in monetized damages to human health and the environment. We model aircraft and ground support equipment emissions at major U.S. airports and estimate the monetized human health and environmental damages of near airport (within 60 miles) emissions. County specific unit damage costs for PM, SOx, NOx, and VOCs and damage valuations for CO and CO2 are used along with aircraft emissions estimations at airports to determine impacts. We find that near-airport emissions at major U.S. airports caused a total of $1.9 billion in damages in 2013, with airports contributing between $720 thousand and $190 million each. These damages vary by airport from $1 to $9 per seat per one-way flight and costs per passenger are often greater than airport charges levied on airlines for infrastructure use. As the U.S. aviation system grows, it is possible to minimize human and environmental costs by shifting aircraft technologies and expanding service into airports where fewer impacts are likely to occur. PMID- 27007188 TI - Alveolar ridge preservation techniques: a systematic review and meta-analysis of histological and histomorphometrical data. AB - AIM: The aim of this article was to systematically review histological and histomorphometrical data from literature that provide information regarding the effect of alveolar ridge preservation procedures on healing after tooth extraction in humans. MATERIALS AND METHODS: The MEDLINE-PubMed and the Cochrane CENTRAL databases were searched up to September 2012; 38 papers were selected from 646 founded. A meta-analysis was performed regarding the variations in the mean percentage of Bone, Connective Tissue and Residual Graft Material between three different types of Procedures. RESULTS: The highest value regarding bone percentages is produced at 3 months by Procedures with Allografts (54.4%), while the lowest is obtained, at 5 months, by those using Xenografts (23.6%). Referring to connective tissue, the highest and lowest values are shown at 7 months, with Allografts (67%) and Alloplasts (27.1%), respectively. Regarding residual graft material, the lowest rates are displayed by Procedures with Allografts (12.4 21.11%), while those using Xenografts and Alloplasts showed the best results at 7 months (37.14 and 37.23%). No statistical difference was found. CONCLUSIONS: With the limitations due to the features of the selected papers, no major histological and histomorphometrical differences arose among different procedures or when compared to spontaneous healing. Thus, it might be argued that in preserved sites it is unnecessary to wait over 3 to 4 months prior to implant insertion. PMID- 27007189 TI - In This Issue: On Biology of Dendritic Cells and B Cells. PMID- 27007190 TI - Dendritic Cells in the Context of Human Tumors: Biology and Experimental Tools. AB - Dendritic cells (DC) are the most potent and versatile antigen-presenting cells (APC) in the immune system. DC have an exceptional ability to comprehend the immune context of a captured antigen based on molecular signals identified from its vicinity. The analyzed information is then conveyed to other immune effector cells. Such capability enables DC to play a pivotal role in mediating either an immunogenic response or immune tolerance towards an acquired antigen. This review summarizes current knowledge on DC in the context of human tumors. It covers the basics of human DC biology, elaborating on the different markers, morphology and function of the different subsets of human DC. Human blood-borne DC are comprised of at least three subsets consisting of one plasmacytoid DC (pDC) and two to three myeloid DC (mDC) subsets. Some tissues have unique DC. Each subset has a different phenotype and function and may induce pro-tumoral or anti-tumoral effects. The review also discusses two methods fundamental to the research of DC on the single-cell level: multicolor flow cytometry (FCM) and image-based cytometry (IC). These methods, along with new genomics and proteomics tools, can provide high-resolution information on specific DC subsets and on immune and tumor cells with which they interact. The different layers of collected biological data may then be integrated using Immune-Cytomics modeling approaches. Such novel integrated approaches may help unravel the complex network of cellular interactions that DC carry out within tumors, and may help harness this complex immunological information into the development of more effective treatments for cancer. PMID- 27007191 TI - Effect of the Proximal Abducting Ulnar Osteotomy on Intra-Articular Pressure Distribution and Contact Mechanics of Congruent and Incongruent Canine Elbows Ex Vivo. AB - OBJECTIVE: To determine the effects of the Proximal Abducting Ulnar Osteotomy (PAUL) on contact pressures of congruent and incongruent (short radius) canine elbows. STUDY DESIGN: Ex vivo biomechanical study. SAMPLE POPULATION: Unpaired normal cadaveric canine forelimbs (n=16). METHODS: A servohydraulic testing frame and thin-film sensors were utilized to measure intra-articular contact area (CA), mean contact pressure (mCP), and peak contact pressure (pCP) for medial and lateral elbow compartments. Percent contribution of the medial compartment relative to the whole (%Med) was also examined. Baseline data were collected in 9 congruent elbows and 7 incongruent elbows where the radius was shortened. Both sets of elbows were tested following ulnar osteotomy and sequential placement of 2 and 3 mm PAUL plates and paw repositioning (to account for any medial to lateral shift of transarticular forces). Paired t-tests compared sequential procedural steps. P<.05 was significant. RESULTS: For congruent elbows, the 2 mm PAUL plate decreased CA in both compartments compared to baseline; lateral pCP increased with subsequent paw repositioning. Induction of radio-ulnar incongruity decreased CA and increased mCP medially, decreased pCP laterally, and increased %MedCA and %MedmCP compared to baseline. Both PAUL plates decreased mCP and pCP medially, with no effect laterally. Paw repositioning had no effect. CONCLUSION: The PAUL procedure had no effect on medial compartment pressure in the congruent elbow. It may ameliorate increased medial compartment pressure in the incongruent elbow. This change does not result from a medial to lateral compartmental shift and deserves further investigation. PMID- 27007192 TI - A New Ba0.6 Sr0.4 TiO3 -Silicon Hybrid Metamaterial Device in Terahertz Regime. AB - Metamaterials, offering unprecedented functionalities to manipulate electromagnetic waves, have become a research hotspot in recent years. Through the incorporation of active media, the exotic electromagnetic behavior of metamaterials can be dramatically empowered by dynamic control. Many ferroelectric materials such as BaSrTiO3 (abbreviated as BST), exhibiting strong response to external electric field, hold great promise in both microwave and terahertz tunable devices. A new active Ba0.6 Sr0.4 TiO3 -silicon hybrid metamaterial device, namely, a SRR (square split-ring resonator)-BaSrTiO3 thin film-silicon three-layer structure is fabricated and intensively studied. The active Ba0.6 Sr0.4 TiO3 thin film hybrid metamaterial, with nanoscale thickness, delivers a transmission contrast up to ~79% due to electrically enabled carrier transport between the ferroelectric thin film and silicon substrate. This work has significantly increased the low modulation rate of ferroelectric based devices in terahertz range, a major problem in this field remaining unresolved for many years. The proposed BST metamaterial is promising in developing high performance real world photonic devices for terahertz technology. PMID- 27007195 TI - Turning up the heat. PMID- 27007194 TI - Lemna minor tolerance to metal-working fluid residues: implications for rhizoremediation. AB - For the first time in the literature, duckweed (Lemna minor) tolerance (alone or in combination with a consortium of bacteria) to spent metal-working fluid (MWF) was assessed, together with its capacity to reduce the chemical oxygen demand (COD) of this residue. In a preliminary study, L. minor response to pre-treated MWF residue (ptMWF) and vacuum-distilled MWF water (MWFw) was tested. Plants were able to grow in both residues at different COD levels tested (up to 2300 mg.l(-1) ), showing few toxicity symptoms (mainly growth inhibition). Plant response to MWFw was more regular and dose responsive than when exposed to ptMWF. Moreover, COD reduction was less significant in ptMWF. Thus, based on these preliminary results, a second study was conducted using MWFw to test the effectiveness of inoculation with a bacterial consortium isolated from a membrane bioreactor fed with the same residue. After 5 days of exposure, COD in solutions containing inoculated plants was significantly lower than in non-inoculated ones. Moreover, inoculation reduced beta+gamma-tocopherol levels in MWFw-exposed plants, suggesting pollutant imposed stress was reduced. We therefore conclude from that L. minor is highly tolerant to spent MWF residues and that this species can be very useful, together with the appropriate bacterial consortium, in reducing COD of this residue under local legislation limits and thus minimise its potential environmental impact. Interestingly, the lipophilic antioxidant tocopherol (especially the sum of beta+gamma isomers) proved to be an effective plant biomarker of pollution. PMID- 27007196 TI - Potential for adaptation in response to thermal stress in an intertidal macroalga. AB - Understanding responses of marine algae to changing ocean temperatures requires knowledge of the impacts of elevated temperatures and the likelihood of adaptation to thermal stress. The potential for rapid evolution of thermal tolerance is dependent on the levels of heritable genetic variation in response to thermal stress within a population. Here, we use a quantitative genetic breeding design to establish whether there is a heritable variation in thermal sensitivity in two populations of a habitat-forming intertidal macroalga, Hormosira banksii (Turner) Descaisne. Gametes from multiple parents were mixed and growth and photosynthetic performance were measured in the resulting embryos, which were incubated under control and elevated temperature (20 degrees C and 28 degrees C). Embryo growth was reduced at 28 degrees C, but significant interactions between male genotype and temperature in one population indicated the presence of genetic variation in thermal sensitivity. Selection for more tolerant genotypes thus has the ability to result in the evolution of increased thermal tolerance. Furthermore, genetic correlations between embryos grown in the two temperatures were positive, indicating that those genotypes that performed well in elevated temperature also performed well in control temperature. Chlorophyll a fluorescence measurements showed a marked decrease in maximum quantum yield of photosystem II (PSII) under elevated temperature. There was an increase in the proportion of energy directed to photoinhibition (nonregulated nonphotochemical quenching) and a concomitant decrease in energy used to drive photochemistry and xanthophyll cycling (regulated nonphotochemical quenching). However, PSII performance between genotypes was similar, suggesting that thermal sensitivity is related to processes other than photosynthesis. PMID- 27007193 TI - Schistosomiasis Prevalence and Intensity of Infection in Latin America and the Caribbean Countries, 1942-2014: A Systematic Review in the Context of a Regional Elimination Goal. AB - BACKGROUND: In 2012 the World Health Assembly adopted resolution WHA65.21 on elimination of schistosomiasis, calling for increased investment in schistosomiasis control and support for countries to initiate elimination programs. This study aims to analyze prevalence and intensity of Schistosoma mansoni infection in children in Latin America and the Caribbean countries and territories (LAC), at the second administrative level or lower. METHODOLOGY: A systematic review of schistosomiasis prevalence and intensity of infection was conducted by searching at PubMed, LILACS and EMBASE. Experts on the topic were informally consulted and institutional web pages were reviewed (PAHO/WHO, Ministries of Health). Only SCH infection among children was registered because it can be a 'proxi-indicator' of recent transmission by the time the study is conducted. PRINCIPAL FINDINGS: One hundred thirty two full-text articles met the inclusion criteria and provided 1,242 prevalence and 199 intensity of infection data points. Most of them were from Brazil (69.7%). Only Brazil published studies after 2001, showing several 'hot spots' with high prevalence. Brazil, Venezuela, Suriname and Saint Lucia need to update the epidemiological status of schistosomiasis to re-design their national programs and target the elimination of Schistosoma mansoni transmission by 2020. In Antigua and Barbuda, Dominican Republic, Guadeloupe, Martinique, Montserrat and Puerto Rico schistosomiasis transmission may be interrupted. However the compilation of an elimination dossier and follow-up surveys, per WHO recommendations, are needed to verify that status. Hence, the burden of subtle SCH chronic infection may be still present and even high in countries that may have eliminated transmission. Heterogeneity in the methodologies used for monitoring and evaluating the progress of the schistosomiasis programs was found, making cross-national and chronological comparisons difficult. CONCLUSIONS: There is a need for updating the schistosomiasis status in the historically endemic countries and territories in LAC to address the required public health interventions for control and elimination programs or to verify the elimination of transmission of Schistosoma mansoni. Improved reporting and standardization of the monitoring and evaluation methodologies used are recommended, while using available WHO guidelines. Meeting a regional elimination goal will require additional and improved epidemiological data by age group and sex. PMID- 27007197 TI - Uptake of iodide in the marine haptophyte Isochrysis sp. (T.ISO) driven by iodide oxidation. AB - Uptake of iodide was studied in the marine microalga Isochrysis sp. (isol. Haines, T.ISO) during short-term incubations with radioactive iodide ((125) I(-) ). Typical inhibitors of the sodium/iodide symporter (NIS) did not inhibit iodide uptake, suggesting that iodide is not taken up through this transport protein, as is the case in most vertebrate animals. Oxidation of iodide was found to be an essential step for its uptake by T.ISO and it seemed likely that hypoiodous acid (HOI) was the form of iodine taken up. Uptake of iodide was inhibited by the addition of thiourea and of other reducing agents, like L-ascorbic acid, L glutathione and L-cysteine and increased after the addition of oxidized forms of the transition metals Fe and Mn. The simultaneous addition of both hydrogen peroxide (H2 O2 ) and a known iodide-oxidizing myeloperoxidase (MPO) significantly increased iodine uptake, but the addition of H2 O2 or MPO separately, had no effect on uptake. This confirms the observation that iodide is oxidized prior to uptake, but it puts into doubt the involvement of H2 O2 excretion and membrane-bound or extracellular haloperoxidase activity of T.ISO. The increase of iodide uptake by T.ISO upon Fe(III) addition suggests the nonenzymatic oxidation of iodide by Fe(III) in a redox reaction and subsequent influx of HOI. This is the first report on the mechanism of iodide uptake in a marine microalga. PMID- 27007198 TI - Production of volatiles by the red seaweed Gelidium arbuscula (Rhodophyta): emission of ethylene and dimethyl sulfide. AB - The effects of different light conditions and exogenous ethylene on the emission of volatile compounds from the alga Gelidium arbuscula Bory de Saint-Vincent were studied. Special emphasis was placed on the possibility that the emission of ethylene and dimethyl sulfide (DMS) are related through the action of dimethylsulfoniopropionate (DMSP) lyase. The conversion of DMSP to DMS and acrylate, which is catalyzed by DMSP lyase, can indirectly support the synthesis of ethylene through the transformation of acrylate to ethylene. After mimicking the desiccation of G. arbuscula thalli experienced during low tides, the volatile compounds emitted were trapped in the headspace of 2 mL glass vials for 1 h. Two methods based on gas chromatography/mass spectrometry revealed that the range of organic volatile compounds released was affected by abiotic factors, such as the availability and spectral quality of light, salinity, and exogenous ethylene. Amines and methyl alkyl compounds were produced after exposure to white light and darkness but not after exposure to exogenous ethylene or red light. Volatiles potentially associated with the oxidation of fatty acids, such as alkenes and low molecular-weight oxygenated compounds, accumu-lated after exposure to exogenous ethylene and red light. Ethylene was produced in all treatments, especially after exposure to exogenous ethylene. Levels of DMS, the most abundant sulfur-compound that was emitted in all of the conditions tested, did not increase after incubation with ethylene. Thus, although DMSP lyase is active in G. arbuscula, it is unlikely to contribute to ethylene synthesis. The generation of ethylene and DMS do not appear to be coordinated in G. arbuscula. PMID- 27007199 TI - CO2 -concentrating mechanisms in three southern hemisphere strains of Emiliania huxleyi. AB - Rising global CO2 is changing the carbonate chemistry of seawater, which is expected to influence the way phytoplankton acquire inorganic carbon. All phytoplankton rely on ribulose-bisphosphate carboxylase oxygenase (RUBISCO) for assimilation of inorganic carbon in photosynthesis, but this enzyme is inefficient at present day CO2 levels. Many algae have developed a range of energy demanding mechanisms, referred to as carbon concentrating mechanisms (CCMs), which increase the efficiency of carbon acquisition. We investigated CCM activity in three southern hemisphere strains of the coccolithophorid Emiliania huxleyi W. W. Hay & H. P. Mohler. Both calcifying and non-calcifying strains showed strong CCM activity, with HCO3 (-) as a preferred source of photosynthetic carbon in the non-calcifying strain, but a higher preference for CO2 in the calcifying strains. All three strains were characterized by the presence of pyrenoids, external carbonic anhydrase (CA) and high affinity for CO2 in photosynthesis, indicative of active CCMs. We postulate that under higher CO2 levels cocco-lithophorids will be able to down-regulate their CCMs, and re-direct some of the metabolic energy to processes such as calcification. Due to the expected rise in CO2 levels, photosynthesis in calcifying strains is expected to benefit most, due to their use of CO2 for carbon uptake. The non-calcifying strain, on the other hand, will experience only a 10% increase in HCO3 (-) , thus making it less responsive to changes in carbonate chemistry of water. PMID- 27007200 TI - Characterization of mycosporine-serine-glycine methyl ester, a major mycosporine like amino acid from dinoflagellates: a mass spectrometry study. AB - Several unknown mycosporine-like amino acids (MAAs) have been previously isolated from some cultured species of toxic dinoflagellates of the Alexandrium genus (Dinophyceae). One of them, originally called M-333, was tentatively identified as a shinorine methyl ester, but the precise nature of this compound is still unknown. Using a high-resolution reversed-phase liquid chromatography mass spectrometry analyses (HPLC/MS), we found that natural populations of the red tide dinoflagellate Prorocentrum micans Ehrenberg showed a net dominance of M-333 together with lesser amounts of other MAAs. We also documented the isolation and characterization of this MAA from natural dinoflagellate populations and from Alexandrium tamarense (Lebour) Balech cultures. Using a comparative fragmentation study in electrospray mass spectrometry between deuterated and non-deuterated M 333 compounds and synthesized mono and dimethyl esters of shinorine, this novel compound was characterized as mycosporine-serine-glycine methyl ester, a structure confirmed by nuclear magnetic resonance. These isobaric compounds can be differentiated by their fragmentation patterns in MS(3) experiments because the extension and the specific site of the methylation changed the fragmentation pathway. PMID- 27007202 TI - Polychlorinated biphenyls disrupt cell division and tip growth in two species of fucoid algae. AB - Environmental contaminants, including poly-chlorinated biphenyls (PCBs), are enriched in coastal sediments, and despite a 1977 moratorium by the United States Environmental Protection Agency on the production of PCBs, levels remain high, more so near former industrial plants. The effects of these contaminants on sessile species in the intertidal zone, particularly nonanimal species such as the ubiquitous fucoid brown algae, are not well known. We investigated the developmental effects of chronic PCB treatment beginning at fertilization on two species of marine rockweed, Fucus vesiculosus Linnaeus and Silvetia compressa (J.Agardh) E.Serrao, T.O.Cho, S.M.Boo & Brawley. A mixture of the most widely used PCB congeners, Aroclors 1221, 1242, and 1254, was delivered at concentrations well below levels found in contaminated sediments, and resulted in severely delayed mitosis and cytokinesis in both species. In F. vesiculosus, this delay was accompanied by abnormal spindle morphology. PCB treatment also dramatically slowed or arrested rhizoid growth after 2-4 d, and by 7 d F. vesiculosus embryos were dead; in contrast, polar secretion of adhesive, germination, and photopolar germination were not affected. The dramatic delay in the first cell division and reduction in tip growth within the first week of development are likely to compromise S. compressa's ability to reproduce and establish new generations. Thus, the data presented here suggest that PCBs still present in coastal sediments may be inhibiting recruitment in these species. Moreover, as sediment dredging causes temporary spikes in PCB concentrations, these kinds of bioremediation steps may exacerbate the disruption of fucoid development. PMID- 27007201 TI - Temperature acclimation and heat tolerance of photosynthesis in Norwegian Saccharina latissima (Laminariales, Phaeophyceae). AB - Kelps, seaweeds and seagrasses provide important ecosystem services in coastal areas, and loss of these macrophytes is a global concern. Recent surveys have documented severe declines in populations of the dominant kelp species, Saccharina latissima, along the south coast of Norway. S. latissima is a cold temperate species, and increasing seawater temperature has been suggested as one of the major causes of the decline. Several studies have shown that S. latissima can acclimate to a wide range of temperatures. However, local adaptations may render the extrapolation of existing results inappropriate. We investigated the potential for thermal acclimation and heat tolerance in S. latissima collected from three locations along the south coast of Norway. Plants were kept in laboratory cultures at three different growth temperatures (10, 15, and 20 degrees C) for 4-6 weeks, after which their photosynthetic performance, fluorescence parameters, and pigment concentrations were measured. S. latissima obtained almost identical photosynthetic characteristics when grown at 10 and 15 degrees C, indicating thermal acclimation at these temperatures. In contrast, plants grown at 20 degrees C suffered substantial tissue deterioration, and showed reduced net photosynthetic capacity caused by a combination of elevated respiration and reduced gross photosynthesis due to lowered pigment concentrations, altered pigment composition, and reduced functionality of Photo system II. Our results support the hypothesis that extraordinarily high temperatures, as observed in 1997, 2002, and 2006, may have initiated the declines in S. latissima populations along the south coast of Norway. However, observations of high mortality in years with low summer temperatures suggest that reduced population resilience or other factors may have contributed to the losses. PMID- 27007203 TI - Transcript patterns of chloroplast-encoded genes in cultured Symbiodinium spp. (Dinophyceae): testing the influence of a light shift and diel periodicity. AB - Microalgae possess numerous cellular mechanisms specifically employed for acclimating the photosynthetic pathways to changes in the physical environment. Despite the importance of coral-dinoflagellate symbioses, little focus has been given as to how the symbiotic algae (Symbiodinium spp.) regulate the expression of their photosynthetic genes. This study used real-time PCR to investigate the transcript abundance of the plastid-encoded genes, psbA (encoding the D1 protein of photosystem II) and psaA (encoding the P700 protein in photosystem I), within the cultured Symbiodinium ITS-2 (internal transcribed spacer region) types A20 and A13. Transcript abundance was monitored during a low to high-light shift, as well as over a full diel light cycle. In addition, psaA was characterized in three isolates (A20, A13, and D4-5) and noted as another example of a dinoflagellate plastid gene encoded on a minicircle. In general, the overall incongruence of transcript patterns for both psbA and psaA between the Symbiodinium isolates and other models of transcriptionally controlled chloroplast gene expression (e.g., Pisum sativum [pea], Sinapis alba [mustard seedling], and Synechocystis sp. PCC 6803 [cyanobacteria]) suggests that Symbiodinium is reliant on posttranscriptional mechanisms for homeostatic regulation of its photosynthetic proteins. PMID- 27007204 TI - Dopamine release by Ulvaria obscura (Chlorophyta): environmental triggers and impacts on photosynthesis, growth, and survival of the releaser. AB - In the NE Pacific, Ulvaria obscura is a common component of "green tide" blooms. It is also the only alga known to produce dopamine, which is released into seawater on sunny days when Ulvaria is emersed and then rehydrated. To better understand the mechanisms associated with dopamine release, we experimentally determined whether light quantity and quality, desiccation, temperature, exudates from conspecifics, and dissolved dopamine caused dopamine release. We also examined the effects of desiccation on Ulvaria's ability to photosynthesize, grow, and survive. Desiccation was the only factor that caused significant amounts of dopamine to be lost from U. obscura tissues. The loss of water from Ulvaria tissues was strongly and positively correlated with the loss of dopamine after rehydration. Only 56% of desiccated algae survived for 1 week, compared to 100% of undesiccated control algae. Desiccated algae lost 77% of their pigmented surface area and grew only 15% as much as undesiccated algae, which remained fully pigmented. The oxygen saturation of water containing Ulvaria that was desiccated and then rehydrated was significantly lower than that of seawater containing undesiccated algae. Thus, desiccation, which is coupled with dopamine release, is associated with the deterioration and death of some, but not all, tissues in Ulvaria. Although dopamine released into seawater can reduce the survival or growth of potential competitors, its release is associated with significant physiological stress and tissue mortality. However, the survival and continued growth of some Ulvaria tissues indicates that a net fitness benefit to release dopamine following desiccation cannot be ruled out. PMID- 27007205 TI - AFLP and SCAR markers associated with the sex in Gracilaria lemaneiformis (Rhodophyta). AB - Gracilaria lemaneiformis (Bory de Saint-Vincent) Greville, an important marine alga, has great economic and nutritional value. However, during the nonreproductive period, it is difficult to distinguish the sporophyte, male gametophyte, and female gametophyte from each other by appearance. Amplified fragment length polymorphism (AFLP) is a multilocus marker technique, which was used in this study to identify markers associated with G. lemaneiformis sex type. By applying 80 primer combinations in the screening process, three fragments were found that were specific to male or female forms of the alga. A 173 bp band and an 89 bp band were found in the sporophyte and the male gametophyte by using primer E-AGG/M-CGT. E-ACC/M-CGG was used to amplify a 118 bp specific fragment in the sporophyte and the female gametophyte. Sequence characterized amplified region (SCAR) primers were designed and showed the expected bands at the corresponding stages. This suggested that the SCAR markers that had been developed were successful. The joint use of the three primer pairs allowed us to characterize sex and the G. lemaneiformis developmental phase in the nondescript stages. Rapid gender testing is expected to improve cross-breeding experiments and other genetic research in this economically important seaweed. PMID- 27007206 TI - Pharmacological investigation of the bioluminescence signaling pathway of the dinoflagellate Lingulodinium polyedrum: evidence for the role of stretch activated ion channels. AB - Dinoflagellate bioluminescence serves as a whole-cell reporter of mechanical stress, which activates a signaling pathway that appears to involve the opening of voltage-sensitive ion channels and release of calcium from intracellular stores. However, little else is known about the initial signaling events that facilitate the transduction of mechanical stimuli. In the present study using the red tide dinoflagellate Lingulodinium polyedrum (Stein) Dodge, two forms of dinoflagellate bioluminescence, mechanically stimulated and spontaneous flashes, were used as reporter systems to pharmacological treatments that targeted various predicted signaling events at the plasma membrane level of the signaling pathway. Pretreatment with 200 MUM Gadolinium III (Gd(3+) ), a nonspecific blocker of stretch-activated and some voltage-gated ion channels, resulted in strong inhibition of both forms of bioluminescence. Pretreatment with 50 MUM nifedipine, an inhibitor of L-type voltage-gated Ca(2+) channels that inhibits mechanically stimulated bioluminescence, did not inhibit spontaneous bioluminescence. Treatment with 1 mM benzyl alcohol, a membrane fluidizer, was very effective in stimulating bioluminescence. Benzyl alcohol-stimulated bioluminescence was inhibited by Gd(3+) but not by nifedipine, suggesting that its role is through stretch activation via a change in plasma membrane fluidity. These results are consistent with the presence of stretch-activated and voltage-gated ion channels in the bioluminescence mechanotransduction signaling pathway, with spontaneous flashing associated with a stretch-activated component at the plasma membrane. PMID- 27007207 TI - Effects of elevated pCO2 on the metabolism of a temperate rhodolith Lithothamnion corallioides grown under different temperatures. AB - Coralline algae are considered among the most sensitive species to near future ocean acidification. We tested the effects of elevated pCO2 on the metabolism of the free-living coralline alga Lithothamnion corallioides ("maerl") and the interactions with changes in temperature. Specimens were collected in North Brittany (France) and grown for 3 months at pCO2 of 380 (ambient pCO2 ), 550, 750, and 1000 MUatm (elevated pCO2 ) and at successive temperatures of 10 degrees C (ambient temperature in winter), 16 degrees C (ambient temperature in summer), and 19 degrees C (ambient temperature in summer +3 degrees C). At each temperature, gross primary production, respiration (oxygen flux), and calcification (alkalinity flux) rates were assessed in the light and dark. Pigments were determined by HPLC. Chl a, carotene, and zeaxanthin were the three major pigments found in L. corallioides thalli. Elevated pCO2 did not affect pigment content while temperature slightly decreased zeaxanthin and carotene content at 10 degrees C. Gross production was not affected by temperature but was significantly affected by pCO2 with an increase between 380 and 550 MUatm. Light, dark, and diel (24 h) calcification rates strongly decreased with increasing pCO2 regardless of the temperature. Although elevated pCO2 only slightly affected gross production in L. corallioides, diel net calcification was reduced by up to 80% under the 1,000 MUatm treatment. Our findings suggested that near future levels of CO2 will have profound consequences for carbon and carbonate budgets in rhodolith beds and for the sustainability of these habitats. PMID- 27007208 TI - Characterization of a novel collagen-like protein TrpA in the cyanobacterium Trichodesmium erythraeum IMS101. AB - The collagen protein family is diverse and its membership is continually expanding as new collagen-like molecules are identified. Identification of collagen in unicellular eukaryotes and prokaryotes has opened discussion on the function of these collagens and their role in the emergence of multicellularity. The previous identification of a collagen gene in Trichodesmium erythraeum raises the question of function of this structural protein in a prokaryote. In this study, we show that this gene is expressed during all phases of growth, indicating that it may be required for all phases of growth. Using immunofluorescence techniques, we demonstrate that the collagen-like protein is localized in a specific manner between adjacent cells along the trichome of T. erythraeum. Trichomes treated with the enzyme collagenase exhibited fragmentation, supporting our immunofluorescence localization data that this collagen-like protein is found between adjacent cells. Our data strongly suggest that the collagen-like protein found in T. erythraeum functions to maintain the structural integrity of the trichome through the adhesion of adjacent cells. PMID- 27007209 TI - The diatom genus Pseudo-nitzschia (Bacillariophyceae) in New South Wales, Australia: morphotaxonomy, molecular phylogeny, toxicity, and distribution. AB - Species belonging to the potentially harmful diatom genus Pseudo-nitzschia, isolated from 16 localities (31 sampling events) in the coastal waters of south eastern Australia, were examined. Clonal isolates were characterized by (i) light and transmission electron microscopy; (ii) phylogenies, based on sequencing of nuclear-encoded ribosomal deoxyribonucleic acid (rDNA) regions and, (iii) domoic acid (DA) production as measured by liquid chromatography-mass spectrometry (LC MS/MS). Ten taxa were unequivocally confirmed as Pseudo-nitzschia americana, P. arenysensis, P. calliantha, P. cuspidata, P. fraudulenta, P. hasleana, P. micropora, P. multiseries, P. multistriata, and P. pungens. An updated taxonomic key for south-eastern Australian Pseudo-nitzschia is presented. The occurrence of two toxigenic species, P. multistriata (maximum concentration 11 pg DA per cell) and P. cuspidata (25.4 pg DA per cell), was documented for the first time in Australia. The Australian strains of P. multiseries, a consistent producer of DA in strains throughout the world, were nontoxic. Data from 5,888 water samples, collected from 31 oyster-growing estuaries (2,000 km coastline) from 2005 to 2009, revealed 310 regulatory exceedances for "Total Pseudo-nitzschia," resulting in six toxic episodes. Further examination of high-risk estuaries revealed that the "P. seriata group" had highest cell densities in the austral summer, autumn, or spring (species dependent), and lowest cell densities in the austral winter, while the "P. delicatissima group" had highest in winter and spring. PMID- 27007210 TI - Whole genome comparison of six Crocosphaera watsonii strains with differing phenotypes. AB - Crocosphaera watsonii, a unicellular nitrogen-fixing cyanobacterium found in oligotrophic oceans, is important in marine carbon and nitrogen cycles. Isolates of C. watsonii can be separated into at least two phenotypes with environmentally important differences, indicating possibly distinct ecological roles and niches. To better understand the evolutionary history and variation in metabolic capabilities among strains and phenotypes, this study compared the genomes of six C. watsonii strains, three from each phenotypic group, which had been isolated over several decades from multiple ocean basins. While a substantial portion of each genome was nearly identical to sequences in the other strains, a few regions were identified as specific to each strain and phenotype, some of which help explain observed phenotypic features. Overall, the small-cell type strains had smaller genomes and a relative loss of genetic capabilities, while the large-cell type strains were characterized by larger genomes, some genetic redundancy, and potentially increased adaptations to iron and phosphorus limitation. As such, strains with shared phenotypes were evolutionarily more closely related than those with the opposite phenotype, regardless of isolation location or date. Unexpectedly, the genome of the type-strain for the species, C. watsonii WH8501, was quite unusual even among strains with a shared phenotype, indicating it may not be an ideal representative of the species. The genome sequences and analyses reported in this study will be important for future investigations of the proposed differences in adaptation of the two phenotypes to nutrient limitation, and to identify phenotype-specific distributions in natural Crocosphaera populations. PMID- 27007211 TI - Novel approach for the development of axenic microalgal cultures from environmental samples. AB - We demonstrated a comprehensive approach for development of axenic cultures of microalgae from environmental samples. A combination of ultrasonication, fluorescence-activated cell sorting (FACS), and micropicking was used to isolate axenic cultures of Chlorella vulgaris Beyerinck (Beijerinck) and Chlorella sorokiniana Shihira & R.W. Krauss from swine wastewater, and Scenedesmus sp. YC001 from an open pond. Ultrasonication dispersed microorganisms attached to microalgae and reduced the bacterial population by 70%, and when followed by cell sorting yielded 99.5% pure microalgal strains. The strains were rendered axenic by the novel method of micropicking and were tested for purity in both solid and liquid media under different trophic states. Denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene confirmed the absence of unculturable bacteria, whereas fluorescence microscopy and scanning electron microscopy (SEM) further confirmed the axenicity. This is the most comprehensive approach developed to date for obtaining axenic microalgal strains without the use of antibiotics and repetitive subculturing. PMID- 27007213 TI - Cost-Utility Analysis of Infliximab with Standard Care versus Standard Care Alone for Induction and Maintenance Treatment of Patients with Ulcerative Colitis in Poland. AB - STUDY OBJECTIVE: To assess the cost-effectiveness of infliximab with standard care (e.g., azathioprine, prednisolone, mesalazine, and 6-mercaptopurine) versus standard care alone for induction and maintenance treatment of patients with ulcerative colitis (UC) in Poland. DESIGN: Cost-utility decision analytic model. MEASUREMENTS AND MAIN RESULTS: A Markov model was used to estimate the expected costs and effects of infliximab/standard care and standard care alone. For each treatment option, costs and quality-adjusted life-years (QALYs) were calculated to estimate the incremental cost-utility ratio. The target population consisted of a hypothetical cohort of adult patients with moderately to severely active UC who had an inadequate response to standard treatment, including corticosteroids and 6-mercaptopurine or azathioprine, or who were intolerant to or had medical contraindications to such therapies. The analysis was performed from the perspective of the Polish public payer over a 30-year time horizon. The clinical parameters were derived mainly from the Active Ulcerative Colitis Trial (ACT) 1 and ACT 2 and from the Ulcerative Colitis Long-term Remission and Maintenance with Adalimumab (ULTRA) 2 clinical trial. Different costs and utility values were assigned to the various health states in the model; utility values were derived from a previously published study. Treatment of patients who received infliximab/standard care instead of standard care alone resulted in 0.174 additional QALYs. Treatment with infliximab/standard care was found to be more expensive than treatment with standard care alone from the Polish National Health Fund perspective. The incremental cost-utility ratio of infliximab/standard care compared with standard care alone was estimated to be 402,420 Polish zlotys (PLN)/QALY gained (95% confidence interval [CI] 253,936-531,450 PLN/QALY gained), which is equivalent to $106,743 (U.S. dollars)/QALY gained (95% CI $67,357 140,968 [U.S. dollars]/QALY gained). CONCLUSION: Treatment with infliximab/standard care instead of standard care alone resulted in additional QALYs but also additional costs. The incremental cost per QALY gained of infliximab/standard care compared with standard care alone exceeded the willingness-to-pay threshold in Poland (equivalent to ~$33,400). PMID- 27007212 TI - Quantification of renal steatosis in type II diabetes mellitus using dixon-based MRI. AB - PURPOSE: To evaluate renal lipid content in subjects with and without type II diabetes mellitus (DM2) using Dixon-based magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study was approved by the Institutional Review Board and compliant with the Health Insurance Portability and Accountability Act. Sixty-nine adults with or without DM2 (n = 29, n = 40) underwent 3T MRI of the abdomen using 3D multiecho Dixon gradient-echo acquisition and proton-density fat fraction (FF) reconstruction. FF values were recorded within segmented regions of interest in the kidneys and liver. The FF measurement error was estimated from the within-subject difference between the right and left kidneys using Bland-Altman analysis. Correlation between renal FF, hepatic FF, and body mass index (BMI) was evaluated. The association between renal FF and DM2 was evaluated by Wilcoxon rank sum test as well as by multivariate regression to correct for potential confounding effects of age, sex, BMI, creatinine, and hepatic FF. P < 0.05 was considered statistically significant. RESULTS: Per-subject 95% limits of agreement of the renal FF measurement were [-3.26%, +3.22%]. BMI was significantly correlated with renal FF (r = 0.266, P = 0.027) and with liver FF (r = 0.344, P = 0.006). Correlation between renal and hepatic FF did not reach statistical significance (r = 0.215, P = 0.090). Median renal FF (+/-interquartile range) was 2.18% (+/-2.52%) in the DM2 cohort, significantly higher than 0.80% (+/-2.63%) in the non-DM2 cohort (P < 0.001). After correcting for potential confounders, the relationship between DM2 and renal FF remained statistically significant (P = 0.005). CONCLUSION: Renal lipid content can be measured noninvasively using Dixon-based MRI and may be increased in subjects with DM2 compared to those without DM2. J. Magn. Reson. Imaging 2016;44:1312-1319. PMID- 27007214 TI - Baromagnetic Effect in Antiperovskite Mn3 Ga0.95 N0.94 by Neutron Powder Diffraction Analysis. AB - A baromagnetic effect in a novel tetragonal magnetic structure is introduced by vacancies in Mn3 Ga0.95 N0.94 , due to the change of the Mn-Mn distance and their spin re-orientation induced by a pressure field. This effect is proven for the first time in antiperovskite compounds by neutron powder diffraction analysis. This feature will enable wide applications in magnetoelectric devices and intelligent instruments. PMID- 27007216 TI - Dietary advice for people with schizophrenia. AB - BACKGROUND: People with serious mental illness have consistently higher levels of mortality and morbidity than the general population. They have greater levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these people, lifestyle and environmental factors such as smoking, obesity, poor diet, and low levels of physical activity play a prominent part. OBJECTIVES: To review the effects of dietary advice for schizophrenia and schizophrenia-like psychosis. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (September 09, 2013 and February 24, 2016). SELECTION CRITERIA: We planned to include all randomised clinical trials focusing on dietary advice versus standard care. DATA COLLECTION AND ANALYSIS: The review authors (RP, KTP) independently screened search results but did not identify any studies that fulfilled the review's criteria. MAIN RESULTS: We did not identify any studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: Dietary advice has been shown to improve the dietary intake of the general population. Research is needed to determine whether dietary advice can have a similar benefit in people with serious mental illness. PMID- 27007215 TI - The natural history of Chlamydia trachomatis infection in women: a multi parameter evidence synthesis. AB - BACKGROUND AND OBJECTIVES: The evidence base supporting the National Chlamydia Screening Programme, initiated in 2003, has been questioned repeatedly, with little consensus on modelling assumptions, parameter values or evidence sources to be used in cost-effectiveness analyses. The purpose of this project was to assemble all available evidence on the prevalence and incidence of Chlamydia trachomatis (CT) in the UK and its sequelae, pelvic inflammatory disease (PID), ectopic pregnancy (EP) and tubal factor infertility (TFI) to review the evidence base in its entirety, assess its consistency and, if possible, arrive at a coherent set of estimates consistent with all the evidence. METHODS: Evidence was identified using 'high-yield' strategies. Bayesian Multi-Parameter Evidence Synthesis models were constructed for separate subparts of the clinical and population epidemiology of CT. Where possible, different types of data sources were statistically combined to derive coherent estimates. Where evidence was inconsistent, evidence sources were re-interpreted and new estimates derived on a post-hoc basis. RESULTS: An internally coherent set of estimates was generated, consistent with a multifaceted evidence base, fertility surveys and routine UK statistics on PID and EP. Among the key findings were that the risk of PID (symptomatic or asymptomatic) following an untreated CT infection is 17.1% [95% credible interval (CrI) 6% to 29%] and the risk of salpingitis is 7.3% (95% CrI 2.2% to 14.0%). In women aged 16-24 years, screened at annual intervals, at best, 61% (95% CrI 55% to 67%) of CT-related PID and 22% (95% CrI 7% to 43%) of all PID could be directly prevented. For women aged 16-44 years, the proportions of PID, EP and TFI that are attributable to CT are estimated to be 20% (95% CrI 6% to 38%), 4.9% (95% CrI 1.2% to 12%) and 29% (95% CrI 9% to 56%), respectively. The prevalence of TFI in the UK in women at the end of their reproductive lives is 1.1%: this is consistent with all PID carrying a relatively high risk of reproductive damage, whether diagnosed or not. Every 1000 CT infections in women aged 16-44 years, on average, gives rise to approximately 171 episodes of PID and 73 of salpingitis, 2.0 EPs and 5.1 women with TFI at age 44 years. CONCLUSIONS AND RESEARCH RECOMMENDATIONS: The study establishes a set of interpretations of the major studies and study designs, under which a coherent set of estimates can be generated. CT is a significant cause of PID and TFI. CT screening is of benefit to the individual, but detection and treatment of incident infection may be more beneficial. Women with lower abdominal pain need better advice on when to seek early medical attention to avoid risk of reproductive damage. The study provides new insights into the reproductive risks of PID and the role of CT. Further research is required on the proportions of PID, EP and TFI attributable to CT to confirm predictions made in this report, and to improve the precision of key estimates. The cost-effectiveness of screening should be re-evaluated using the findings of this report. FUNDING: The Medical Research Council grant G0801947. PMID- 27007217 TI - Antimicrobial dressings for the prevention of catheter-related infections in newborn infants with central venous catheters. AB - BACKGROUND: Central venous catheters (CVCs) provide secured venous access in neonates. Antimicrobial dressings applied over the CVC sites have been proposed to reduce catheter-related blood stream infection (CRBSI) by decreasing colonisation. However, there may be concerns on the local and systemic adverse effects of these dressings in neonates. OBJECTIVES: We assessed the effectiveness and safety of antimicrobial (antiseptic or antibiotic) dressings in reducing CVC related infections in newborn infants. Had there been relevant data, we would have evaluated the effects of antimicrobial dressings in different subgroups, including infants who received different types of CVCs, infants who required CVC for different durations, infants with CVCs with and without other antimicrobial modifications, and infants who received an antimicrobial dressing with and without a clearly defined co-intervention. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2015, Issue 9), MEDLINE (PubMed), EMBASE (EBCHOST), CINAHL and references cited in our short listed articles using keywords and MeSH headings, up to September 2015. SELECTION CRITERIA: We included randomised controlled trials that compared an antimicrobial CVC dressing against no dressing or another dressing in newborn infants. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the CNRG. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using risk difference (RD) and risk ratio (RR) with 95% confidence intervals (CIs). MAIN RESULTS: Out of 173 articles screened, three studies were included. There were two comparisons: chlorhexidine dressing following alcohol cleansing versus polyurethane dressing following povidone-iodine cleansing (one study); and silver-alginate patch versus control (two studies). A total of 855 infants from level III neonatal intensive care units (NICUs) were evaluated, 705 of whom were from a single study. All studies were at high risk of bias for blinding of care personnel or unclear risk of bias for blinding of outcome assessors. There was moderate-quality evidence for all major outcomes.The single study comparing chlorhexidine dressing/alcohol cleansing against polyurethane dressing/povidone-iodine cleansing showed no significant difference in the risk of CRBSI (RR 1.18, 95% CI 0.53 to 2.65; RD 0.01, 95% CI -0.02 to 0.03; 655 infants, moderate-quality evidence) and sepsis without a source (RR 1.06, 95% CI 0.75 to 1.52; RD 0.01, 95% CI -0.04 to 0.06; 705 infants, moderate-quality evidence). There was a significant reduction in the risk of catheter colonisation favouring chlorhexidine dressing/alcohol cleansing group (RR 0.62, 95% CI 0.45 to 0.86; RD -0.09, 95% CI -0.15 to -0.03; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 7 to 33; 655 infants, moderate-quality evidence). However, infants in the chlorhexidine dressing/alcohol cleansing group were significantly more likely to develop contact dermatitis, with 19 infants in the chlorhexidine dressing/alcohol cleansing group having developed contact dermatitis compared to none in the polyurethane dressing/povidone-iodine cleansing group (RR 43.06, 95% CI 2.61 to 710.44; RD 0.06, 95% CI 0.03 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 13 to 33; 705 infants, moderate-quality evidence). The roles of chlorhexidine dressing in the outcomes reported were unclear, as the two assigned groups received different co-interventions in the form of different skin cleansing agents prior to catheter insertion and during each dressing change.In the other comparison, silver-alginate patch versus control, the data for CRBSI were analysed separately in two subgroups as the two included studies reported the outcome using different denominators: one using infants and another using catheters. There were no significant differences between infants who received silver-alginate patch against infants who received standard line dressing in CRBSI, whether expressed as the number of infants (RR 0.50, 95% CI 0.14 to 1.78; RD -0.12, 95% CI -0.33 to 0.09; 1 study, 50 participants, moderate-quality evidence) or as the number of catheters (RR 0.72, 95% CI 0.27 to 1.89; RD -0.05, 95% CI -0.20 to 0.10; 1 study, 118 participants, moderate-quality evidence). There was also no significant difference between the two groups in mortality (RR 0.55, 95% CI 0.15 to 2.05; RD -0.04, 95% CI -0.13 to 0.05; two studies, 150 infants, I2 = 0%, moderate-quality evidence). No adverse skin reaction was recorded in either group. AUTHORS' CONCLUSIONS: Based on moderate-quality evidence, chlorhexidine dressing/alcohol skin cleansing reduced catheter colonisation, but made no significant difference in major outcomes like sepsis and CRBSI compared to polyurethane dressing/povidone-iodine cleansing. Chlorhexidine dressing/alcohol cleansing posed a substantial risk of contact dermatitis in preterm infants, although it was unclear whether this was contributed mainly by the dressing material or the cleansing agent. While silver alginate patch appeared safe, evidence is still insufficient for a recommendation in practice. Future research that evaluates antimicrobial dressing should ensure blinding of caregivers and outcome assessors and ensure that all participants receive the same co-interventions, such as the skin cleansing agent. Major outcomes like sepsis, CRBSI and mortality should be assessed in infants of different gestation and birth weight. PMID- 27007219 TI - The First Estimates of Marbled Cat Pardofelis marmorata Population Density from Bornean Primary and Selectively Logged Forest. AB - The marbled cat Pardofelis marmorata is a poorly known wild cat that has a broad distribution across much of the Indomalayan ecorealm. This felid is thought to exist at low population densities throughout its range, yet no estimates of its abundance exist, hampering assessment of its conservation status. To investigate the distribution and abundance of marbled cats we conducted intensive, felid focused camera trap surveys of eight forest areas and two oil palm plantations in Sabah, Malaysian Borneo. Study sites were broadly representative of the range of habitat types and the gradient of anthropogenic disturbance and fragmentation present in contemporary Sabah. We recorded marbled cats from all forest study areas apart from a small, relatively isolated forest patch, although photographic detection frequency varied greatly between areas. No marbled cats were recorded within the plantations, but a single individual was recorded walking along the forest/plantation boundary. We collected sufficient numbers of marbled cat photographic captures at three study areas to permit density estimation based on spatially explicit capture-recapture analyses. Estimates of population density from the primary, lowland Danum Valley Conservation Area and primary upland, Tawau Hills Park, were 19.57 (SD: 8.36) and 7.10 (SD: 1.90) individuals per 100 km2, respectively, and the selectively logged, lowland Tabin Wildlife Reserve yielded an estimated density of 10.45 (SD: 3.38) individuals per 100 km2. The low detection frequencies recorded in our other survey sites and from published studies elsewhere in its range, and the absence of previous density estimates for this felid suggest that our density estimates may be from the higher end of their abundance spectrum. We provide recommendations for future marbled cat survey approaches. PMID- 27007218 TI - A Versatile Vector for In Vivo Monitoring of Type I Interferon Induction and Signaling. AB - Development of reporter systems for in vivo examination of IFN-beta induction or signaling of type I interferon (IFN-I) pathways is of great interest in order to characterize biological responses to different inducers such as viral infections. Several reporter mice have been developed to monitor the induction of both pathways in response to different agonists. However, alternative strategies that do not require transgenic mice breeding have to date not been reported. In addition, detection of these pathways in vivo in animal species other than mice has not yet been addressed. Herein we describe a simple method based on the use of an adeno-associated viral vector (AAV8-3xIRF-ISRE-Luc) containing an IFN-beta induction and signaling-sensitive promoter sequence controlling the expression of the reporter gene luciferase. This vector is valid for monitoring IFN-I responses in vivo elicited by diverse stimuli in different organs. Intravenous administration of the vector in C57BL/6 mice and Syrian hamsters was able to detect activation of the IFN pathway in the liver upon systemic treatment with different pro-inflammatory agents and infection with Newcastle disease virus (NDV). In addition, intranasal instillation of AAV8-3xIRF-ISRE-Luc showed a rapid and transient IFN-I response in the respiratory tract of mice infected with the influenza A/PR8/34 virus lacking the NS1 protein. In comparison, this response was delayed and exacerbated in mice infected with influenza A/PR/8 wild type virus. In conclusion, the AAV8-3xIRF-ISRE-Luc vector offers the possibility of detecting IFN-I activation in response to different stimuli and in different animal models with no need for reporter transgenic animals. PMID- 27007220 TI - Top-Down Processes in Simulated Electric-Acoustic Hearing: The Effect of Linguistic Context on Bimodal Benefit for Temporally Interrupted Speech. AB - OBJECTIVES: Previous studies have documented the benefits of bimodal hearing as compared with a cochlear implant alone, but most have focused on the importance of bottom-up, low-frequency cues. The purpose of the present study was to evaluate the role of top-down processing in bimodal hearing by measuring the effect of sentence context on bimodal benefit for temporally interrupted sentences. It was hypothesized that low-frequency acoustic cues would facilitate the use of contextual information in the interrupted sentences, resulting in greater bimodal benefit for the higher context (CUNY) sentences than for the lower context (IEEE) sentences. DESIGN: Young normal-hearing listeners were tested in simulated bimodal listening conditions in which noise band vocoded sentences were presented to one ear with or without low-pass (LP) filtered speech or LP harmonic complexes (LPHCs) presented to the contralateral ear. Speech recognition scores were measured in three listening conditions: vocoder-alone, vocoder combined with LP speech, and vocoder combined with LPHCs. Temporally interrupted versions of the CUNY and IEEE sentences were used to assess listeners' ability to fill in missing segments of speech by using top-down linguistic processing. Sentences were square-wave gated at a rate of 5 Hz with a 50% duty cycle. Three vocoder channel conditions were tested for each type of sentence (8, 12, and 16 channels for CUNY; 12, 16, and 32 channels for IEEE) and bimodal benefit was compared for similar amounts of spectral degradation (matched channel comparisons) and similar ranges of baseline performance. Two gain measures, percentage-point gain and normalized gain, were examined. RESULTS: Significant effects of context on bimodal benefit were observed when LP speech was presented to the residual-hearing ear. For the matched-channel comparisons, CUNY sentences showed significantly higher normalized gains than IEEE sentences for both the 12-channel (20 points higher) and 16-channel (18 points higher) conditions. For the individual gain comparisons that used a similar range of baseline performance, CUNY sentences showed bimodal benefits that were significantly higher (7% points, or 15 points normalized gain) than those for IEEE sentences. The bimodal benefits observed here for temporally interrupted speech were considerably smaller than those observed in an earlier study that used continuous speech. Furthermore, unlike previous findings for continuous speech, no bimodal benefit was observed when LPHCs were presented to the LP ear. CONCLUSIONS: Findings indicate that linguistic context has a significant influence on bimodal benefit for temporally interrupted speech and support the hypothesis that low-frequency acoustic information presented to the residual hearing ear facilitates the use of top-down linguistic processing in bimodal hearing. However, bimodal benefit is reduced for temporally interrupted speech as compared with continuous speech, suggesting that listeners' ability to restore missing speech information depends not only on top-down linguistic knowledge but also on the quality of the bottom-up sensory input. PMID- 27007221 TI - Preparation of nanoliposome loaded with peanut peptide fraction: stability and bioavailability. AB - Nanoliposome loaded with peanut peptide fraction (PPF) prepared by high pressure microfluidization (HPM) treatment was investigated as well as its stability and bioavailability. PPF showed hydrophilicity character with a solubility of 97.50 +/- 2.31 mg mL(-1) in aqueous solution. HPM treatment can prepare nanoliposome but decreased encapsulation efficiency (EE). A pressure of 120 MPa was the appropriate parameter where the particle size and EE of nanolipsome was 79.67 +/- 1.85 nm and 65.12 +/- 2.96%, respectively. Crude liposome and nanoliposome both showed good stability under different pH conditions, even at pH value of 2.0. Nanoliposome behaved better in vitro controlled release than crude liposome. Most important of all, nanoliposome had the highest angiotension converting enzyme (ACE) inhibitory activity after simulated gastrointestinal tract (GIT) digestion. Morphology of digested liposome proved that nanoliposome can keep relative integrity in structure although it suffered a lot of attack. PMID- 27007222 TI - Correlation of Insulin Resistance with Anthropometric Measures and Blood Pressure in Adolescents. AB - BACKGROUND: Blood pressure is directly related to body mass index, and individuals with increased waist circumference have higher risk of developing hypertension, insulin resistance, and other metabolic changes, since adolescence. OBJECTIVE: to evaluate the correlation of blood pressure with insulin resistance, waist circumference and body mass index in adolescents. METHODS: Cross-section study on a representative sample of adolescent students. One group of adolescents with altered blood pressure detected by casual blood pressure and/or home blood pressure monitoring (blood pressure > 90th percentile) and one group of normotensive adolescents were studied. Body mass index, waist circumference were measured, and fasting glucose and plasma insulin levels were determined, using the HOMA-IR index to identify insulin resistance. RESULTS: A total of 162 adolescents (35 with normal blood pressure and 127 with altered blood pressure) were studied; 61% (n = 99) of them were boys and the mean age was 14.9 +/- 1.62 years. Thirty-eight (23.5%) adolescents had altered HOMA-IR. The group with altered blood pressure had higher values of waist circumference, body mass index and HOMA-IR (p<0.05). Waist circumference was higher among boys in both groups (p<0.05) and girls with altered blood pressure had higher HOMA-IR than boys (p<0.05). There was a significant moderate correlation between body mass index and HOMA-IR in the group with altered blood pressure (rho = 0.394; p < 0.001), and such correlation was stronger than in the normotensive group. There was also a significant moderate correlation between waist circumference and HOMA-IR in both groups (rho = 0.345; p < 0.05). Logistic regression showed that HOMA-IR was as predictor of altered blood pressure (odds ratio - OR = 2.0; p = 0.001). CONCLUSION: There was a significant association of insulin resistance with blood pressure and the impact of insulin resistance on blood pressure since childhood. The correlation and association between markers of cardiovascular diseases was more pronounced in adolescents with altered blood pressure, suggesting that primary prevention strategies for cardiovascular risk factors should be early implemented in childhood and adolescence. PMID- 27007223 TI - Potential Utility of the SYNTAX Score 2 in Patients Undergoing Left Main Angioplasty. AB - BACKGROUND: The revascularization strategy of the left main disease is determinant for clinical outcomes. OBJECTIVE: We sought to 1) validate and compare the performance of the SYNTAX Score 1 and 2 for predicting major cardiovascular events at 4 years in patients who underwent unprotected left main angioplasty and 2) evaluate the long-term outcome according to the SYNTAX score 2 recommended revascularization strategy. METHODS: We retrospectively studied 132 patients from a single-centre registry who underwent unprotected left main angioplasty between March 1999 and December 2010. Discrimination and calibration of both models were assessed by ROC curve analysis, calibration curves and the Hosmer-Lemeshow test. RESULTS: Total event rate was 26.5% at 4 years.The AUC for the SYNTAX Score 1 and SYNTAX Score 2 for percutaneous coronary intervention, was 0.61 (95% CI: 0.49-0.73) and 0.67 (95% CI: 0.57-0.78), respectively. Despite a good overall adjustment for both models, the SYNTAX Score 2 tended to underpredict risk. In the 47 patients (36%) who should have undergone surgery according to the SYNTAX Score 2, event rate was numerically higher (30% vs. 25%; p=0.54), and for those with a higher difference between the two SYNTAX Score 2 scores (Percutaneous coronary intervention vs. Coronary artery by-pass graft risk estimation greater than 5.7%), event rate was almost double (40% vs. 22%; p=0.2). CONCLUSION: The SYNTAX Score 2 may allow a better and individualized risk stratification of patients who need revascularization of an unprotected left main coronary artery. Prospective studies are needed for further validation. PMID- 27007224 TI - Cardiac Autonomic Adjustments During Baroreflex Test in Obese and Non-Obese Preadolescents. AB - BACKGROUND: Recent studies have shown changes in cardiac autonomic control of obese preadolescents. OBJECTIVE: To assess the heart rate responses and cardiac autonomic modulation of obese preadolescents during constant expiratory effort. METHODS: This study assessed 10 obese and 10 non-obese preadolescents aged 9 to 12 years. The body mass index of the obese group was between the 95th and 97th percentiles of the CDC National Center for Health Statistics growth charts, while that of the non-obese group, between the 5th and 85th percentiles. Initially, they underwent anthropometric and clinical assessment, and their maximum expiratory pressures were obtained. Then, the preadolescents underwent a constant expiratory effort of 70% of their maximum expiratory pressure for 20 seconds, with heart rate measurement 5 minutes before, during and 5 minutes after it. Heart rate variability (HRV) and heart rate values were analyzed by use of a software. RESULTS: The HRV did not differ when compared before and after the constant expiratory effort intra- and intergroup. The heart rate values differed (p < 0.05) during the effort, being the total variation in non-obese preadolescents of 18.5 +/- 1.5 bpm, and in obese, of 12.2 +/- 1.3 bpm. CONCLUSION: The cardiac autonomic modulation did not differ between the groups when comparing before and after the constant expiratory effort. However, the obese group showed lower cardiovascular response to baroreceptor stimuli during the effort, suggesting lower autonomic baroreflex sensitivity. PMID- 27007225 TI - Fattening Up Allograft Rejection. PMID- 27007227 TI - Regulatory T Cells in Chronic Graft-Versus-Host Disease After Extracorporeal Photopheresis: Correlation With Skin and Global Organ Responses, and Ability to Taper Steroids. AB - BACKGROUND: Induction of immune tolerance by an increase in regulatory T (Treg) cells after extracorporeal photopheresis (ECP) is thought to contribute to how ECP exerts its therapeutic effect in patients with chronic graft-versus-host disease (cGvHD). We investigated whether percentages and absolute counts of Treg cells changed post-ECP, and examined correlation with response. METHODS: Absolute counts and % of CD4+ T cells and Treg cells (CD4 + CD25 + FOXP3 + CD127dim/-) were evaluated using flow cytometry in 32 patients with cGvHD treated by ECP for a minimum of 3 months, and up to 12 months. CD4+ or Treg cells at baseline to 12 months post-ECP were compared with changes in skin disease scores or global organ involvement, or the ability to taper steroids, at 14, 28, and 56 weeks. RESULTS: Regulatory T cells % increased significantly above any overall changes in CD4+ % at 6, 9, and 12 months post-ECP. There was no statistically significant association between Treg cells and skin or steroid response, whereas a larger increase in CD4+ count from baseline to 1 to 3 months corresponded to increased odds of being able to reduce steroid dose by 50% or greater at 14 weeks. Skin and global organ responders at 28 weeks had higher median Treg cell counts 3 months post-ECP than nonresponders, as did steroid responders at 56 weeks who were 12 months post-ECP. CONCLUSIONS: Regulatory T cell counts and % varied greatly among cGvHD patients, and the increase post-ECP was not significant until 6 months. No clear correlation was found between Treg cells and clinical improvement, suggesting that increases in Treg cell numbers and/or proportions are not driving the mechanism leading to a response after ECP. PMID- 27007226 TI - High-Fat Diet-Induced Obesity Enhances Allograft Rejection. AB - BACKGROUND: Obesity promotes a state of low-grade inflammation that exacerbates chronic inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation, the survival of organs transplanted into obese patients is reduced compared with allografts in lean recipients. However, whether this is due to increased alloimmunity remains to be addressed conclusively. METHODS: We used a mouse model of high-fat diet (HFD)-induced obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic splenocyte immunization in vivo, and allogeneic heart transplantation. RESULTS: Our results indicate that HFD altered the composition and phenotype of splenic antigen-presenting cells that led to their enhanced capacity to stimulate T cells. Immunization with allogeneic splenocytes in vivo resulted in increased alloreactivity, as determined by IFNgamma production. Moreover, cardiac allograft rejection in HFD mice was modestly accelerated compared to aged-matched control animals fed a low fat diet, correlating with enhanced alloreactive T cell function. CONCLUSIONS: Our results highlight the increased alloresponse triggered by HFD-induced obesity and its negative impact on transplant outcome. PMID- 27007228 TI - Authors' Response. PMID- 27007229 TI - Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL 6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities. AB - To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-alpha (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP. PMID- 27007230 TI - Obstetric Outcomes of Mothers Previously Exposed to Sexual Violence. AB - BACKGROUND: There is a scarcity of data on the association of sexual violence and women's subsequent obstetric outcomes. Our aim was to investigate whether women exposed to sexual violence as teenagers (12-19 years of age) or adults present with different obstetric outcomes than women with no record of such violence. METHODS: We linked detailed prospectively collected information on women attending a Rape Trauma Service (RTS) to the Icelandic Medical Birth Registry (IBR). Women who attended the RTS in 1993-2010 and delivered (on average 5.8 years later) at least one singleton infant in Iceland through 2012 formed our exposed cohort (n = 1068). For each exposed woman's delivery, nine deliveries by women with no RTS attendance were randomly selected from the IBR (n = 9126) matched on age, parity, and year and season of delivery. Information on smoking and Body mass index (BMI) was available for a sub-sample (n = 792 exposed and n = 1416 non-exposed women). Poisson regression models were used to estimate Relative Risks (RR) with 95% confidence intervals (CI). RESULTS: Compared with non-exposed women, exposed women presented with increased risks of maternal distress during labor and delivery (RR 1.68, 95% CI 1.01-2.79), prolonged first stage of labor (RR 1.40, 95% CI 1.03-1.88), antepartum bleeding (RR 1.95, 95% CI 1.22-3.07) and emergency instrumental delivery (RR 1.16, 95% CI 1.00-1.34). Slightly higher risks were seen for women assaulted as teenagers. Overall, we did not observe differences between the groups regarding the risk of elective cesarean section (RR 0.86, 95% CI 0.61-1.21), except for a reduced risk among those assaulted as teenagers (RR 0.56, 95% CI 0.34-0.93). Adjusting for maternal smoking and BMI in a sub-sample did not substantially affect point estimates. CONCLUSION: Our prospective data suggest that women with a history of sexual assault, particularly as teenagers, are at increased risks of some adverse obstetric outcomes. PMID- 27007231 TI - Clinical Profile of Cyclooxygenase-2 Inhibitors in Treating Non-Small Cell Lung Cancer: A Meta-Analysis of Nine Randomized Clinical Trials. AB - BACKGROUND: Evidence on the benefits of combining cyclooxygenase-2 inhibitor (COX 2) in treating non-small cell lung cancer (NSCLC) is still controversial. We investigated the efficacy and safety profile of cyclooxygenase-2 inhibitors in treating NSCLC. METHODS: The first meta-analysis of eligible studies was performed to assess the effect of COX-2 inhibitors for patients with NSCLC on the overall response rate (ORR), overall survival (OS), progression-free survival (PFS), one-year survival, and toxicities. The fixed-effects model was used to calculate the pooled RR and HR and between-study heterogeneity was assessed. Subgroup analyses were conducted according to the type of COX-2 inhibitors, treatment pattern, and treatment line. RESULTS: Nine randomized clinical trials, comprising 1679 patents with NSCLC, were included in the final meta-analysis. The pooled ORR of patients who have NSCLC with COX-2 inhibitors was significantly higher than that without COX-2 inhibitors. In subgroup analysis, significantly increased ORR results were found on celecoxib (RR = 1.29, 95% CI: 1.09, 1.51), rofecoxib (RR = 1.61, 95% CI: 1.14, 2.28), chemotherapy (RR = 1.40, 95% CI: 1.20, 1.63), and first-line treatment (RR = 1.39, 95% CI: 1.19, 1.63). However, COX-2 inhibitors had no effect on the one-year survival, OS, and PFS. Increased RR of leucopenia (RR = 1.21, 95% CI: 1.01, 1.45) and thrombocytopenia (RR = 1.36, 95% CI: 1.06, 1.76) suggested that COX-2 inhibitors increased hematologic toxicities (grade >= 3) of chemotherapy. CONCLUSIONS: COX-2 inhibitors increased ORR of advanced NSCLC and had no impact on survival indices, but it may increase the risk of hematologic toxicities associated with chemotherapy. PMID- 27007233 TI - Assessing Seasonal and Inter-Annual Variations of Lake Surface Areas in Mongolia during 2000-2011 Using Minimum Composite MODIS NDVI. AB - A minimum composite method was applied to produce a 15-day interval normalized difference vegetation index (NDVI) dataset from Moderate Resolution Imaging Spectroradiometer (MODIS) daily 250 m reflectance in the red and near-infrared bands. This dataset was applied to determine lake surface areas in Mongolia. A total of 73 lakes greater than 6.25 km2in area were selected, and 28 of these lakes were used to evaluate detection errors. The minimum composite NDVI showed a better detection performance on lake water pixels than did the official MODIS 16 day 250 m NDVI based on a maximum composite method. The overall lake area detection performance based on the 15-day minimum composite NDVI showed -2.5% error relative to the Landsat-derived lake area for the 28 evaluated lakes. The errors increased with increases in the perimeter-to-area ratio but decreased with lake size over 10 km(2). The lake area decreased by -9.3% at an annual rate of 53.7 km(2) yr(-1) during 2000 to 2011 for the 73 lakes. However, considerable spatial variations, such as slight-to-moderate lake area reductions in semi-arid regions and rapid lake area reductions in arid regions, were also detected. This study demonstrated applicability of MODIS 250 m reflectance data for biweekly monitoring of lake area change and diagnosed considerable lake area reduction and its spatial variability in arid and semi-arid regions of Mongolia. Future studies are required for explaining reasons of lake area changes and their spatial variability. PMID- 27007232 TI - Association between Smoking Status and Obesity in a Nationwide Survey of Japanese Adults. AB - OBJECTIVE: A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population. METHODS: We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index >= 25kg/m2) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation. RESULTS: In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72-0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09-1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55 years had an elevated OR of 1.60 (95% CI:1.05-2.38) for obesity. CONCLUSIONS: In a general Japanese population, obesity is progressively associated with pack years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered. PMID- 27007235 TI - Question About the Analysis of Missing Data and Identification of an Error-Reply. PMID- 27007236 TI - A Financial Market Model Incorporating Herd Behaviour. AB - Herd behaviour in financial markets is a recurring phenomenon that exacerbates asset price volatility, and is considered a possible contributor to market fragility. While numerous studies investigate herd behaviour in financial markets, it is often considered without reference to the pricing of financial instruments or other market dynamics. Here, a trader interaction model based upon informational cascades in the presence of information thresholds is used to construct a new model of asset price returns that allows for both quiescent and herd-like regimes. Agent interaction is modelled using a stochastic pulse-coupled network, parametrised by information thresholds and a network coupling probability. Agents may possess either one or two information thresholds that, in each case, determine the number of distinct states an agent may occupy before trading takes place. In the case where agents possess two thresholds (labelled as the finite state-space model, corresponding to agents' accumulating information over a bounded state-space), and where coupling strength is maximal, an asymptotic expression for the cascade-size probability is derived and shown to follow a power law when a critical value of network coupling probability is attained. For a range of model parameters, a mixture of negative binomial distributions is used to approximate the cascade-size distribution. This approximation is subsequently used to express the volatility of model price returns in terms of the model parameter which controls the network coupling probability. In the case where agents possess a single pulse-coupling threshold (labelled as the semi-infinite state-space model corresponding to agents' accumulating information over an unbounded state-space), numerical evidence is presented that demonstrates volatility clustering and long-memory patterns in the volatility of asset returns. Finally, output from the model is compared to both the distribution of historical stock returns and the market price of an equity index option. PMID- 27007241 TI - Current Options for Third-Line Treatment of Metastatic Colorectal Cancer. AB - Until recently, treatment options for patients with metastatic colorectal cancer (CRC) were limited to chemotherapy, vascular endothelial growth factor-targeted therapy, and, for patients with RAS-wild type tumors, epidermal growth factor receptor-targeted therapy. For patients with disease progression after treatment, newer agents are now available: the multitargeted tyrosine kinase inhibitor regorafenib and the cytotoxic combination of trifluridine and tipiracil (TAS 102). Both regorafenib and trifluridine/tipiracil have demonstrated significant improvements in overall survival in patients with refractory metastatic CRC. Durable responses exceeding a year have been reported with regorafenib. The agents differ in their safety profiles. Regorafenib is associated with hand-foot skin reaction and fatigue, primarily in the first cycle. Alternative dosing strategies appear to improve the tolerability of regorafenib, and randomized dosing studies are underway to define the optimal strategy. Trifluridine/tipiracil is associated primarily with myelosuppression. Sequencing of these agents can be guided by patient characteristics, such as comorbidities and adverse reactions to previous treatments. Patients with a poor performance status are not likely to benefit from regorafenib. Ongoing studies are further defining the role of regorafenib and trifluridine/tipiracil in the treatment of metastatic CRC. PMID- 27007237 TI - Reproducibility of Resting State Connectivity in Patients with Stable Multiple Sclerosis. AB - Given increasing efforts to use resting-state fMRI (rfMRI) as a biomarker of disease progression in multiple sclerosis (MS) we here explored the reproducibility of longitudinal rfMRI over three months in patients with clinically and radiologically stable MS. To pursue this aim, two approaches were applied in nine rfMRI networks: First, the intraclass correlation coefficient (ICC 3,1) was assessed for the mean functional connectivity maps across the entire network and a region of interest (ROI). Second, the ratio of overlap between Z-thresholded connectivity maps for each network was assessed. We quantified between-session functional reproducibility of rfMRI for 20 patients with stable MS and 14 healthy controls (HC). Nine rfMRI networks (RSNs) were examined at baseline and after 3 months of follow-up: three visual RSNs, the default-mode network, sensorimotor-, auditory-, executive control, and the left and right fronto-parietal RSN. ROI analyses were constrained to thresholded overlap masks for each individual (Z>0) at baseline and follow-up.In both stable MS and HC mean functional connectivity across the entire network did not reach acceptable ICCs for several networks (ICC<0.40) but we found a high reproducibility of ROI ICCs and of the ratio of overlap. ROI ICCs of all nine networks were between 0.98 and 0.99 for HC and ranged from 0.88 to 0.99 in patients with MS, respectively. The ratio of overlap for all networks was similar for both groups, ranging from 0.60 to 0.75.Our findings attest to a high reproducibility of rfMRI networks not only in HC but also in patients with stable MS when applying ROI analysis. This supports the utility of rfMRI to monitor functional changes related to disease progression or therapeutic interventions in MS. PMID- 27007242 TI - Challenges of small-pixel infrared detectors: a review. AB - In the last two decades, several new concepts for improving the performance of infrared detectors have been proposed. These new concepts particularly address the drive towards the so-called high operating temperature focal plane arrays (FPAs), aiming to increase detector operating temperatures, and as a consequence reduce the cost of infrared systems. In imaging systems with the above megapixel formats, pixel dimension plays a crucial role in determining critical system attributes such as system size, weight and power consumption (SWaP). The advent of smaller pixels has also resulted in the superior spatial and temperature resolution of these systems. Optimum pixel dimensions are limited by diffraction effects from the aperture, and are in turn wavelength-dependent. In this paper, the key challenges in realizing optimum pixel dimensions in FPA design including dark current, pixel hybridization, pixel delineation, and unit cell readout capacity are outlined to achieve a sufficiently adequate modulation transfer function for the ultra-small pitches involved. Both photon and thermal detectors have been considered. Concerning infrared photon detectors, the trade-offs between two types of competing technology-HgCdTe material systems and III-V materials (mainly barrier detectors)-have been investigated. PMID- 27007234 TI - Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women. AB - IMPORTANCE: A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age. OBJECTIVE: To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets. DESIGN, SETTING, AND PARTICIPANTS: This investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study. MAIN OUTCOMES AND MEASURES: We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age. RESULTS: We observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. CONCLUSIONS AND RELEVANCE: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers. PMID- 27007243 TI - Sandfly fauna (Diptera: Psychodidae) from caves in the state of Rondonia, Brazil. AB - This study had the aim of ascertaining the sandfly fauna and possible presence of Leishmania in these insects, collected in caves in the state of Rondonia, Brazil. Collections were conducted in eight caves located in two different areas of this state. Leishmania in the sandflies collected was detected using the polymerase chain reaction (PCR). This was the first study on sandflies from caves in Rondonia and, among the total of 1,236 individuals collected, 24 species and 10 genera were identified. The species Evandromyia georgii was collected for the first time in Rondonia and the most abundant species were Trichophoromyia ubiquitalis with 448 individuals (36.2%), followed by T. octavioi with 283 (22.9%) and E. georgii with 179 (14.5%). For the PCR, 17 pools were analyzed and five pools were positive (forT. auraensis in three pools and for Nyssomyia shawi and N. antunesi in one pool each). The kDNA region was amplified and the presence of Leishmania DNA was confirmed. The sandfly fauna in these caves can be considered diverse in comparison with similar studies in other regions. It may be that some species use caves as a temporary shelter and breeding site, while other species live exclusively in this environment. The detection of Leishmania DNA indicates that this pathogen is circulating in cave environments and that further studies are needed in order to ascertain the risks of infection by leishmaniasis in these locations with high touristic potential. PMID- 27007244 TI - Epizootiology of Perkinsus sp. inCrassostrea gasar oysters in polyculture with shrimps in northeastern Brazil. AB - Bivalve culture is of considerable economic and social interest in northeastern (NE) Brazil. The polyculture is an alternative approach to traditional monoculture for reducing the environmental impact of shrimp farming and improving oyster culture. Perkinsus marinus and Perkinsus olseni were found infecting oysters in NE Brazil and can threaten oyster production. This study evaluated Perkinsus spp. occurrence in Crassostrea gasar during all production stages. Oyster spats were produced in a hatchery and grown in shrimp ponds in Rio Grande do Norte state. Perkinsus spp. were surveyed by Ray's fluid thioglycollate medium and confirmed by polymerase chain reaction. Prevalence and intensity of infection were determined in oysters until they reached 7 cm. Results showed that the broodstock was already infected by Perkinsus (60%), but the derived spats were Perkinsus-free. Oyster spats acquired Perkinsus infection when transferred to ponds. The prevalence gradually increased in the seven months following placement in ponds (73%), and then decreased to 17% by the tenth month. The infections were initially mild, but intensity increased at the final growth stage. In conclusion, it is possible to produce Perkinsus-free C. gasar oyster spats from infected broodstock, and their culture in shrimp ponds is feasible. PMID- 27007245 TI - Molecular phylogeny of Toxoplasmatinae: comparison between inferences based on mitochondrial and apicoplast genetic sequences. AB - Phylogenies within Toxoplasmatinae have been widely investigated with different molecular markers. Here, we studied molecular phylogenies of the Toxoplasmatinae subfamily based on apicoplast and mitochondrial genes. Partial sequences of apicoplast genes coding for caseinolytic protease (clpC) and beta subunit of RNA polymerase (rpoB), and mitochondrial gene coding for cytochrome B (cytB) were analyzed. Laboratory-adapted strains of the closely related parasites Sarcocystis falcatula and Sarcocystis neurona were investigated, along with Neospora caninum, Neospora hughesi, Toxoplasma gondii (strains RH, CTG and PTG), Besnoitia akodoni, Hammondia hammondiand two genetically divergent lineages of Hammondia heydorni. The molecular analysis based on organellar genes did not clearly differentiate between N. caninum and N. hughesi, but the two lineages of H. heydorni were confirmed. Slight differences between the strains of S. falcatula and S. neurona were encountered in all markers. In conclusion, congruent phylogenies were inferred from the three different genes and they might be used for screening undescribed sarcocystid parasites in order to ascertain their phylogenetic relationships with organisms of the family Sarcocystidae. The evolutionary studies based on organelar genes confirm that the genus Hammondia is paraphyletic. The primers used for amplification of clpC and rpoB were able to amplify genetic sequences of organisms of the genus Sarcocystisand organisms of the subfamily Toxoplasmatinae as well. PMID- 27007246 TI - Parasite load in intact and ulcerative skin of dogs with leishmaniais. AB - The skin is the site of inoculation of Leishmania spp. in susceptible hosts, and consequently dermatopathies, especially ulcerative dermatitis, are the main clinical signs observed. The aim of this study was to assess parasitism of the skin (intact and ulcerated) among dogs that were naturally infected by Leishmania spp., through immunohistochemical analysis. Skin fragments (intact and ulcerated) were collected from 13 dogs with positive parasitological (bone marrow aspiration and exfoliative skin) and serological examinations (ELISA S7 Biogene) for Leishmania spp. These samples were processed using the immunohistochemical technique, involving the streptavidin-peroxidase complex. Ulcerative lesions were mainly observed on the elbows (53.84%; 7/13), nostrils (15.38%; 2/13), ears (23.07%; 3/13) and wings of the ilium (7.69%; 1/13). A severe parasite load was detected in 46.15% and 76.92% of the intact and ulcerated skin samples tested, respectively. The parasite load on ulcerated skin was statistically higher than on intact skin (p = 0.0221). These results indicate that the intact and ulcerated skin may host a high parasite load of amastigote forms of Leishmania spp., which can favor the transmission of the parasite. PMID- 27007247 TI - New records for Amblyomma sculptum (Ixodidae) on non-passerine birds in Brazil. AB - The aim of this paper was to provide new records of Amblyomma sculptum on two species of terricolous birds in two areas of the Cerrado (savannah- like) bioma: two specimens of Cariama cristata were captured in the state of Goias and one specimen ofCrax fasciolata was captured in the state of Minas Gerais. One of the C. cristata was parasitized by 15 larvae, six nymphs, one male and two females whereas the C. fasciolata was parasitized by seven larvae and eight nymphs. This paper presents a new locality for occurrence of parasitism A. sculptum in C. cristata and a new host for C fasciolata. PMID- 27007248 TI - Are similar the parasite communities structure of Trachelyopterus coriaceus and Trachelyopterus galeatus (Siluriformes: Auchenipteridae) in the Amazon basin? AB - The aim of this study was to compare the parasite communities in two sympatric host populations, Trachelyopterus coriaceus andTrachelyopterus galeatus, which were caught in tributary of the Amazon River in Brazil. All the specimens of T. galeatusand T. coriaceus were infected by one or more parasites, such as Ichthyophthirius multifiliis, Tripartiella tetramerii, Trichodina nobilis, Cosmetocleithrum striatuli, Contracaecumsp., Cystidicoloides sp., Dadaytremoides parauchenipteri and Gorytocephalus spectabilis. Seven species were common to both host fish, and there were 1-5 parasite species per host. In both hosts, trichodinids were dominant. Aggregate dispersion of ectoparasites and endoparasites was observed, with greater aggregation among endoparasites. Only the ectoparasites species showed differences in intensity and/or abundance. However, the parasite communities of the two hosts were taxonomically similar (99%) and characterized by high prevalence and high abundance of ectoparasites, but with low diversity, prevalence and abundance of endoparasites. Trachelyopterus galeatus, the host with the larger body size, presented greater variation of Brillouin diversity and evenness, while T. coriaceus had higher Berger-Parker dominance values and total numbers of parasites. This first study on these parasites ofT. galeatus and T. coriaceus showed that the life mode, size of the hosts and the availability of infective forms of the parasites were the main factors that influenced the parasite communities structure. PMID- 27007249 TI - Evaluation of clinical signs, parasitemia, hematologic and biochemical changes in cattle experimentally infected with Trypanosoma vivax. AB - Infections by Trypanosoma vivax cause great losses to livestock in Africa and Central and South Americas. Outbreaks due this parasite have been occurred with increasing frequency in Brazil. Knowledge of changes caused by T. vivax during the course of this disease can be of great diagnostic value. Thus, clinical signs, parasitemia, hematologic and biochemical changes of cattle experimentally infected by this hemoparasite were evaluated. Two distinct phases were verified during the infection - an acute phase where circulating parasites were seen and then a chronic phase where fluctuations in parasitemia were detected including aparasitemic periods. A constant reduction in erythrocytes, hemoglobin and packed cell volume (PVC) were observed. White blood cells (WBC) showed pronounced changes such as severe neutropenia and lymphopenia during the acute phase of the illness. Decreases in cholesterol, albumin, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and increases in glucose, globulin, protein, and alkaline phosphatase (ALP) were observed. The "Lins" isolate of T. vivax showed pathogenicity for cattle, and intense parasitemia was detected in the early stages of infection. Circulating parasites were detected for about two months. The most evident laboratory abnormalities were found in WBC parameters, including thrombocytopenia. PMID- 27007250 TI - Occurrence of anti-Toxoplasma gondii antibodies and parasite DNA in backyard chicken breeding in Northeast, Brazil. AB - The aim of the present study was to investigate the occurrence of anti-Toxoplasma gondii antibodies and parasite DNA in backyard chickens bred in the metropolitan area of Recife, Brazil. In total, 212 serum samples were collected from 16 properties, and 12 backyard chickens were collected in the six sanitary districts of Recife. An indirect immunofluorescence assay (IFA) was used to investigate the occurrence of anti-Toxoplasma gondii antibodies. Polymerase chain reaction (PCR) was used to detect T. gondii DNA in brain, heart, liver and lung specimens. Of the samples analyzed by serology, 86/212 (40.56%) were positive; of the samples analyzed by PCR, 2/12 (16.7%) were positive, with both samples positive by both tests (serological and molecular). The presence of antibody anti-T. gondii and parasite DNA in tissues of these animals are worrying aspects for public health because there is a risk of transmission of the parasite to humans through eating undercooked or raw meat. Based on the results, the adoption of preventive measures to prevent the cats access to the chickens creations should be encouraged, since these animals were identified in most of the studied properties. PMID- 27007251 TI - Incorporation of photo-carbon monoxide releasing materials into electrospun scaffolds for vascular tissue engineering. AB - Hyper-proliferation of smooth muscle cells (SMCs) and a reduction in endothelial cell function are reasons for poor patency rates of current tissue engineered small-diameter vascular grafts. The controlled delivery of carbon monoxide (CO), a gasotransmitter involved in cell signaling, could improve vascular cell function in these grafts. Current CO releasing molecules (CORMs) can improve endothelialization of injured vessels with appropriate doses, but they still have limitations. The goal of this project was to generate a novel tissue engineered scaffold that includes a non-toxic and photoactivatable CORM. This is the first use of a CORM for tissue engineering. The results demonstrated that CORM-loaded, electrospun poly(E-caprolactone) scaffolds can be photo-activated and release CO. The fluorescence that develops after CO release can be used to non-destructively track the extent of reaction. Further, activation can occur when both dry and incubated in cell culture conditions. However, incubation in serum protein containing media decreases the time frame for activation, demonstrating the importance of testing the release profile in culture conditions. Rat SMCs were able to attach, grow, and express contractile SMC markers on activated CORM loaded meshes and controls. Overall, these findings demonstrate that CORM-loaded electrospun scaffolds provide a promising delivery system for vascular tissue engineering. PMID- 27007253 TI - Factors Associated with Knowledge and Personal Protective Behavior Related to Avian Influenza A (H7N9) Risk among Chinese Poultry Farmers. PMID- 27007252 TI - Activation of Plant Innate Immunity by Extracellular High Mobility Group Box 3 and Its Inhibition by Salicylic Acid. AB - Damage-associated molecular pattern molecules (DAMPs) signal the presence of tissue damage to induce immune responses in plants and animals. Here, we report that High Mobility Group Box 3 (HMGB3) is a novel plant DAMP. Extracellular HMGB3, through receptor-like kinases BAK1 and BKK1, induced hallmark innate immune responses, including i) MAPK activation, ii) defense-related gene expression, iii) callose deposition, and iv) enhanced resistance to Botrytis cinerea. Infection by necrotrophic B. cinerea released HMGB3 into the extracellular space (apoplast). Silencing HMGBs enhanced susceptibility to B. cinerea, while HMGB3 injection into apoplast restored resistance. Like its human counterpart, HMGB3 binds salicylic acid (SA), which results in inhibition of its DAMP activity. An SA-binding site mutant of HMGB3 retained its DAMP activity, which was no longer inhibited by SA, consistent with its reduced SA-binding activity. These results provide cross-kingdom evidence that HMGB proteins function as DAMPs and that SA is their conserved inhibitor. PMID- 27007254 TI - The Influence of U.S. Chain Restaurant Food Consumption and Obesity in China and South Korea: An Ecological Perspective of Food Consumption, Self-Efficacy in Weight Management, Willingness to Communicate About Weight/Diet, and Depression. AB - This study examined the impact of U.S. chain restaurant food consumption in China and South Korea from an ecological perspective. Specifically, it explored the relationships among several environmental and individual variables that have been found to affect obesity/weight management in previous research, including the prevalence/popularity of U.S. chain restaurants in these countries, frequency of U.S. chain restaurant food consumption, self-efficacy in weight management, willingness to communicate about weight/diet, self-perceptions of weight/obesity stigma, body mass index (BMI), and depression. The results indicated that willingness to communicate about weight/diet predicted increased self-efficacy in weight management. Higher BMI scores were found to predict increased weight/obesity stigma, and increased frequency of U.S. restaurant food consumption, weight/obesity stigma, and reduced self-efficacy in weight management were found to predict increased levels of depression. The theoretical and practical implications of the findings are discussed, along with limitations and directions for future research. PMID- 27007255 TI - Spanish Adaptation and Validation of the Short Internalized Homonegativity Scale (SIHS). AB - Internalized homophobia has been related to mental health problems and sexual risk behaviors among nonheterosexual people. This article validates the Spanish adaptation of the Short Internalized Homonegativity Scale (SIHS). For this purpose, 347 men and 183 women completed the instrument. Exploratory factorial analysis showed three factors: public identification as homosexual (PIH), sexual comfort with homosexual people (SEXC), and social comfort with homosexual people (SOCC). These factors explained 57.96% of total variance. In addition, confirmatory factorial analysis supported this structure and internal consistency (Cronbach's alpha) was.80 for the full scale. The three subscales ranged from.70 to.79. Convergent validity showed a positive correlation between the SIHS and depressive symptoms, and negative correlation with condom use, self-esteem, and having sex after alcohol consumption. In conclusion, the SIHS could be an accurate instrument to evaluate internalized homophobia among the Spanish population. PMID- 27007256 TI - Internet-based self-help treatment for panic disorder: a randomized controlled trial comparing mandatory versus optional complementary psychological support. AB - Panic disorder (PD) is one of the most common psychiatric disorders. Web-based self-help treatments for PD have had promising results. These online treatments seem to have larger effect sizes (ESs) when professional support is added. However, the amount of support or how it should be administered is not yet clear. The aim of this trial was to study two ways of administering psychological support provided by phone as a part of Internet-based self-help treatment for PD based on cognitive behavioral therapy. Seventy-seven participants diagnosed with PD were randomly assigned to one of three experimental conditions: a waiting list control group; a treatment group with non-scheduled psychological support; or a treatment group with scheduled psychological support. PD symptoms of participants who received treatment improved significantly compared to the control group (mean ES d = 1.18, p < .05). In addition, there were statistically and clinically significant differences between treatment groups (Mean difference = -3.20, p = .005, 95% CI [-5.62, -.79]). The scheduled group showed a larger ES, a lower dropout rate, and better adherence to treatment than the non-scheduled group. Scheduled support seems to be indicated for patients who seek Web-based treatment for PD, and their symptoms of panic, anxiety, and depression improve at post treatment and six-month follow-up. In contrast, when support depends on patient demand, they receive less support and so, the therapeutic effect is poorer. PMID- 27007258 TI - Fecal Carriage of Extended-Spectrum beta-Lactamases in Healthy Humans, Poultry, and Wild Birds in Leon, Nicaragua-A Shared Pool of blaCTX-M Genes and Possible Interspecies Clonal Spread of Extended-Spectrum beta-Lactamases-Producing Escherichia coli. AB - Antibiotic-resistant bacteria are a major concern in the healthcare of today, especially the increasing number of gram-negative bacteria producing beta lactamases such as extended-spectrum beta-lactamases (ESBLs). However, little is known about the relationship of ESBL producers in humans and domestic and wild birds, especially in a low-income setting. Therefore, we studied the fecal carriage of ESBL-producing Escherichia coli and Klebsiella pneumoniae in healthy humans, poultry, and wild birds in the vicinity of Leon, Nicaragua. Three hundred fecal samples were collected during December 2012 from humans (n = 100), poultry (n = 100) and wild birds (n = 100). The samples were examined for ESBL-producing E. coli and K. pneumoniae, revealing the prevalence of 27% in humans, 13% in poultry, and 8% in wild birds. Further characterization of the ESBL-producing isolates was performed through polymerase chain reaction (PCR) (NDM, CTX-M), epidemiological typing (ERIC2-PCR), multilocus sequence typing, and sequencing. ESBL producers harbored blaCTX-M-2, blaCTX-M-15, blaCTX-M-22, and blaCTX-M-3 genotypes. The blaCTX-M-15 constituted the absolute majority of ESBL genes among all samples. ERIC-PCR demonstrated highly related E. coli clones among humans, poultry, and wild birds. Clinically relevant E. coli clone ST648 was found in humans and poultry. There is a shared pool of blaCTX-M genes between humans and domesticated and wild birds in Nicaragua, and the results suggest shared clones of ESBL-producing E. coli. The study adds to the notion that wild birds and poultry can pick up antibiotic-resistant bacteria of human origin and function as a melting pot of resistance. Structured surveillance programs of antimicrobial resistance and a more regulated prescription of antibiotics are warranted in Nicaragua. PMID- 27007257 TI - Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case-Control Pilot Study. AB - OBJECTIVE: This case-control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD. METHODS: We studied youth with ASD aged 11-18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS. RESULTS: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons. CONCLUSION: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing. PMID- 27007259 TI - From phylogeny into ontogeny with Claes Hellerstrom. PMID- 27007260 TI - A Novel CD4+ T Cell-Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology. AB - RATIONALE: Infection with Pneumocystis, an opportunistic fungal pathogen, can result in fulminant pneumonia in the clinical setting of patients with immunosuppression. In murine models, Pneumocystis has previously been shown to induce a CD4+ T cell-dependent eosinophilic response in the lung capable of providing protection. OBJECTIVES: We sought to explore the role of Pneumocystis in generating asthma-like lung pathology, given the natural eosinophilic response to infection. METHODS: Pneumocystis infection or antigen treatment was used to induce asthma-like pathology in wild-type mice. The roles of CD4+ T cells and eosinophils were examined using antibody depletion and knockout mice, respectively. The presence of anti-Pneumocystis antibodies in human serum samples was detected by ELISA and Western blotting. MEASUREMENTS AND MAIN RESULTS: Pneumocystis infection generates a strong type II response in the lung that requires CD4+ T cells. Pneumocystis infection was capable of priming a Th2 response similar to that of a commonly studied airway allergen, the house dust mite. Pneumocystis antigen treatment was also capable of inducing allergic inflammation in the lung, resulting in anti-Pneumocystis IgE production, goblet cell hyperplasia, and increased airway resistance. In the human population, patients with severe asthma had increased levels of anti-Pneumocystis IgG and IgE compared with healthy control subjects. Patients with severe asthma with elevated anti-Pneumocystis IgG levels had worsened symptom scores and lung parameters such as decreased forced expiratory volume and increased residual volume compared with patients with severe asthma who had low anti-Pneumocystis IgG. CONCLUSIONS: The present study demonstrates for the first time, to our knowledge, that Pneumocystis is an airway allergen capable of inducing asthma-like lung pathology. PMID- 27007262 TI - Corrigendum. PMID- 27007261 TI - Mode Switching and Filtering in Nanowire Lasers. AB - Coherent light sources confining the light below the vacuum wavelength barrier will drive future concepts of nanosensing, nanospectroscopy, and photonic circuits. Here, we directly image the angular emission of such a light source based on single semiconductor nanowire lasers. It is confirmed that the lasing switches from the fundamental mode in a thin ZnO nanowire to an admixture of several transverse modes in thicker nanowires approximately at the multimode cutoff. The mode competition with higher order modes substantially slows down the laser dynamics. We show that efficient photonic mode filtering in tapered nanowires selects the desired fundamental mode for lasing with improved performance including power, efficiency, and directionality important for an optimal coupling between adjacent nanophotonic waveguides. PMID- 27007263 TI - Optic pathway glioma in children: 10 years of experience in a single institution. AB - Optic pathway glioma (OPG) is a rare brain tumor that occurs more commonly during early childhood and is frequently associated with neurofibromatosis type 1 (NF1). In this study, our aim was to describe the characteristics, management, and outcome of patients with OPG. We retrospectively analyzed the clinical charts of all children diagnosed with OPG at our institution from 2003 to 2013. Twenty children (11 boys and 9 girls, median age: 5 and 3/12 years; NF1: 15/20) were diagnosed with OPG. The diagnosis was based on magnetic resonance imaging (MRI) findings. A biopsy was useful in 3 patients. The main reason for seeking medical advice was decreased vision (7/20 patients), whereas in 10/20 patients, the diagnosis was established during the routine follow-up for their NF1. Fifteen patients demonstrated MRI findings of optic nerve involvement and/or chiasmal tumor, whereas in 5 children, postchiasmal structures were also involved. Sixteen patients (16/20) received carboplatin-based regimens, whereas 4/20 patients were only under close observation. Six patients showed deterioration of visual acuity and/or imaging findings at the end of treatment and/or during their follow-up. Three of them (3/6) underwent tumor resection, whereas 1 (1/6) received radiation treatment. None of our patients had total blindness from both eyes. Half of our patients were diagnosed during follow-up for their NF1, the incidence of which was high in our group. Our data suggest that chemotherapy helps in the preservation of vision in the majority of children. PMID- 27007267 TI - Membrane Sterols Modulate the Binding Mode of Amphotericin B without Affecting Its Affinity for a Lipid Bilayer. AB - Membrane-active antibiotics are known to selectively target certain pathogens based on cell membrane properties, such as fluidity, lipid ordering, and phase behavior. These are in turn modulated by the composition of a lipid bilayer and in particular by the presence and type of membrane sterols. Amphotericin B (AmB), the golden standard of antifungal treatment, exhibits higher activity toward ergosterol-rich fungal membranes, which permits its use against systemic mycoses; however, the selectivity for fungal membranes is far from satisfactory leading to severe side effects. Despite decades of research, no consensus has emerged on the origin of AmB specificity for fungal cells and its actual mode of action at the molecular level. Previously, it has been proposed that the specific action of AmB is related to differences in its affinity for membranes of different composition. In this work, we investigate this relationship by employing molecular dynamics simulations to compare the free energy of insertion of AmB into three types of membranes: a pure DMPC bilayer and DMPC bilayers containing 30% of cholesterol or ergosterol. We analyze the orientation of AmB molecules within the bilayer in order to unambiguously establish their membrane binding mode and relate the orientational freedom to the sterol-dependent tightness of lipid packing. Our results strongly indicate that the membrane insertion of AmB proceeds virtually to completion independent of membrane type, and hence the higher toxicity against fungal membranes may rather result from differences in subsequent oligomerization in the membrane and assembly of monomers into functional transmembrane pores. In particular, the latter could be facilitated by sterol-induced ordering of AmB molecules along the membrane normal, revealed by our free energy profiles. Moreover--in contrast to certain claims--we find no stable binding mode corresponding to the horizontal adsorption of AmB on the membrane surface. PMID- 27007268 TI - IS SAME-DAY INGUINAL HERNIA SURGERY POSSIBLE? AB - : 1-INTRODUCTION: The Lichtenstein hernia repair is associated with low recurrence rates and short operation times, and can be performed under local anaesthesia. Thus, this is among the most-preferred methods used in recent years. Our objective was to explore the same-day discharge rates, and the causes of delayed discharge and re-admission to hospital, of patients treated using the Lichtenstein repair method, to evaluate the feasibility of performing same-day hernia surgery in clinical practice. 2. MATERIALS AND METHODS: . One hundredof a total of 236 patients diagnosed with unilateral inguinal or femoral hernias, who required surgical treatment, and who agreed with the conditions of the study, were prospectively included. All patients were treated using the Lichtenstein mesh repair method, under local anaesthesia between June 2006 and January 2008. We investigated the types and locations of hernias, duration of surgery, seniority of the surgeon, the feasibility of same-day surgery in subgroups stratified by ASA risk scores, and postoperative complication rates, in patients who underwent inguinal surgery under local anaesthesia 3. RESULTS , DISCUSSION AND CONCLUSIONS:. The rates of pain and post-operative complications were very low in hernia patients who underwent same-day surgery under local anaesthesia. The operation reduces the length of hospital stay and helps patients mobilise earlier. Both the literature, and our data, indicate that inguinal hernia repair under local anaesthesia is safe and effective, reducing anaesthesia-related complications and the length of hospital stay; is cost-effective; and is applicable in all patients. PMID- 27007269 TI - FDG-PET-based differential uptake volume histograms: a possible approach towards definition of biological target volumes. AB - OBJECTIVE: Integration of fluorine-18 fludeoxyglucose ((18)F-FDG)-positron emission tomography (PET) functional data into conventional anatomically based gross tumour volume delineation may lead to optimization of dose to biological target volumes (BTV) in radiotherapy. We describe a method for defining tumour subvolumes using (18)F-FDG-PET data, based on the decomposition of differential uptake volume histograms (dUVHs). METHODS: For 27 patients with histopathologically proven non-small-cell lung carcinoma (NSCLC), background uptake values were sampled within the healthy lung contralateral to a tumour in those image slices containing tumour and then scaled by the ratio of mass densities between the healthy lung and tumour. Signal-to-background (S/B) uptake values within volumes of interest encompassing the tumour were used to reconstruct the dUVHs. These were subsequently decomposed into the minimum number of analytical functions (in the form of differential uptake values as a function of S/B) that yielded acceptable net fits, as assessed by chi(2) values. RESULTS: Six subvolumes consistently emerged from the fitted dUVHs over the sampled volume of interest on PET images. Based on the assumption that each function used to decompose the dUVH may correspond to a single subvolume, the intersection between the two adjacent functions could be interpreted as a threshold value that differentiates them. Assuming that the first two subvolumes spread over the tumour boundary, we concentrated on four subvolumes with the highest uptake values, and their S/B thresholds [mean +/- standard deviation (SD)] were 2.88 +/- 0.98, 4.05 +/- 1.55, 5.48 +/- 2.06 and 7.34 +/- 2.89 for adenocarcinoma, 3.01 +/- 0.71, 4.40 +/- 0.91, 5.99 +/- 1.31 and 8.17 +/- 2.42 for large-cell carcinoma and 4.54 +/- 2.11, 6.46 +/- 2.43, 8.87 +/- 5.37 and 12.11 +/- 7.28 for squamous cell carcinoma, respectively. CONCLUSION: (18)F-FDG-based PET data may potentially be used to identify BTV within the tumour in patients with NSCLC. Using the one-way analysis of variance statistical tests, we found a significant difference among all threshold levels among adenocarcinomas, large-cell carcinoma and squamous cell carcinomas. On the other hand, the observed significant variability in threshold values throughout the patient cohort (expressed as large SDs) can be explained as a consequence of differences in the physiological status of the tumour volume for each patient at the time of the PET/CT scan. This further suggests that patient-specific threshold values for the definition of BTVs could be determined by creation and curve fitting of dUVHs on a patient-by-patient basis. ADVANCES IN KNOWLEDGE: The method of (18)F-FDG-PET-based dUVH decomposition described in this work may lead to BTV segmentation in tumours. PMID- 27007270 TI - Healthy Lifestyle Pattern is Protective Against 30-Yr Cancer Incidence in Men and Women: A Cohort Study. AB - OBJECTIVES: Investigate associations of healthier behaviors with 30-yr cancer incidence. SUBJECTS/METHODS: In 1982, 632 healthy men and women (ages 40-70) were interviewed for nutritional habits using a Food Frequency Questionnaire and a 24 h physical activity questionnaire. Blood pressure, weight, and height were measured, and blood was drawn for biochemical profiles. Thirteen and four subjects were excluded due to cancer diagnosis <=1 yr from recruitment and extreme values of reported total daily calorie intake, respectively. RESULTS: During a mean follow-up of 24.2 yr, 146 cancer incident patients (23.7%) were documented. Total cancer risk was 38% lower in the medium vegetable intake tertile [adjusted hazards ratio (HR) = 0.62, 95%confidence interval (CI): 0.40 0.95], and 66% higher in the medium fruit intake tertile (adjusted HR = 1.66, 95%CI: 1.08-2.55) compared to the lowest tertile. The risk of gastrointestinal cancers was 3 times greater for the highest, compared to the lowest, dairy consumption tertile (HR = 3.06, 95%CI: 1.01-9.23). "Healthy lifestyle" (normal BMI, never smoked, consuming high levels of dietary fiber and vegetables, and more physically active) reduced overall cancer risk (adjusted HR = 0.63, 95%CI: 0.44-0.91) as compared to the rest of the cohort. CONCLUSIONS: Our findings reinforce the importance of lifestyle-related factors, which are relatively low cost and may contribute to reduction in the burden of malignant diseases. PMID- 27007271 TI - Fentanyl Buccal Soluble Film: A Review in Breakthrough Cancer Pain. AB - Fentanyl buccal soluble film (Onsolis((r)), Breakyl((r)), PainkylTM) comprises two layers: a mucoadhesive layer containing the active drug, and an inactive layer with the aim of preventing the diffusion of fentanyl into the oral cavity. It is approved in several countries worldwide, including the USA and those of the EU, for the management of breakthrough cancer pain in opioid-tolerant, adult patients with cancer. This article reviews the pharmacological properties of fentanyl buccal soluble film and its clinical efficacy and tolerability in these patients. Fentanyl buccal soluble film provides an additional option for transmucosal delivery of fentanyl, with approximately half of the dose undergoing an initial, rapid absorption via the buccal mucosa (accounting for its high bioavailability). In clinical trials, fentanyl buccal soluble film was associated with significant improvements in pain intensity scores versus placebo and was generally well tolerated. The most common adverse events were typical opioid associated adverse events, such as nausea and vomiting. Fentanyl buccal soluble film is a useful option for the treatment of breakthrough cancer pain in opioid tolerant patients. PMID- 27007272 TI - Intraperitoneal Ropivacaine Irrigation in Patients Undergoing Bariatric Surgery: a Prospective Randomized Clinical Trial. AB - BACKGROUND: Despite most bariatric procedures are actually performed by laparoscopic approach, management of postoperative pain remains a major challenge. The aim of this study was to analyze the analgesic effect of intraperitoneal ropivacaine infusion in patients undergoing bariatric surgery. METHODS: A prospective randomized clinical trial of all the patients undergoing laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) between January and November 2015 was performed. Patients were randomized to experimental (EG: those patients undergoing intraperitoneal ropivacain irrigation) and control groups (CG: those undergoing intraperitoneal irrigation with normal saline). RESULTS: One hundred ten patients were included, 83 LRYGB (75.5 %) and 27 LSG (24.5 %). Mean pain, as measured by VAS score, was 21.7 +/- 14.5 mm in CG and 13.3 +/- 10.9 mm in EG (p = 0.002). Morphine needs during the first 24 h postoperatively were 21.8 % in CG and 3.6 % in EG (p = 0.01). Early taking of fluids by mouth was possible 6 h after surgery in 76.4 % in EG vs 34.5 % in CG (p = 0.001). Early mobilization ability (6 h after surgery) was feasible in 72.7 % in EG and 32.7 % in CG (p = 0.001). Median hospital stay was 3 days (range 2-10 days) in CG and 2 days (2-7 days) in EG (p = 0.009). CONCLUSIONS: The intraoperative peritoneal infusion with ropivacaine in patients undergoing bariatric surgery is associated with a reduction in postoperative pain, lower morphine needs, earlier mobilization and earlier oral intake of fluids after surgery, and a shorter hospital stay. ClinicalTrials.gov Identifier: NCT02641288. PMID- 27007273 TI - Unravelling the relationship between macroautophagy and mitochondrial ROS in cancer therapy. AB - Macroautophagy (Autophagy), an evolutionarily conserved cellular self-digesting process implicated in various physiological and pathological processes, is activated by different stimuli including oxidative stress. Reactive oxygen species (ROS) are involved in autophagy modulation through multiple signaling pathways and transcription regulators. Accumulating data support both a positive and negative role of ROS-modulated autophagy in cancer. As a tumor suppressive mechanism, autophagy induces autophagic cell death and maintains genome stability. Conversely, autophagy may promote cancer development by limiting metabolic stress and supplying high-energetic nutrients. Mitochondrial ROS (mitoROS), the main source of endogenous ROS, serve as essential signal transducers that mediate autophagy, while autophagy can also regulate mitochondrial ROS generation in turn. Here, we untangle the knot between mitochondrial ROS and autophagy, which may be of great significance to solve the conundrum of the inter-conversion between cytoprotective and cytotoxic roles of autophagy; thus providing new insights for current cancer therapies. Whilst, we focus on anti-tumor agents that target mitoROS-regulated autophagy, in the hope of fueling the exploration of more potential novel anti-cancer drugs in the future. PMID- 27007275 TI - Evaluation of estimation, prediction and inference for autocorrelated latent variable modeling of binary data-a simulation study. AB - Longitudinal models of binary or ordered categorical data are often evaluated for adequacy by the ability of these to characterize the transition frequency and type between response states. Drug development decisions are often concerned with accurate prediction and inference of the probability of response by time and dose. A question arises on whether the transition probabilities need to be characterized adequately to ensure accurate response prediction probabilities unconditional on the previous response state. To address this, a simulation study was conducted to assess bias in estimation, prediction and inferences of autocorrelated latent variable models (ALVMs) when the transition probabilities are misspecified due to ill-posed random effects structures, inadequate likelihood approximation or omission of the autocorrelation component. The results may be surprising in that these suggest that characterizing autocorrelation in ALVMs is not as important as specifying a suitably rich random effects structure. PMID- 27007274 TI - Use of Salivary Diurnal Cortisol as an Outcome Measure in Randomised Controlled Trials: a Systematic Review. AB - BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with diverse adverse health outcomes, making it an important therapeutic target. Measurement of the diurnal rhythm of cortisol secretion provides a window into this system. At present, no guidelines exist for the optimal use of this biomarker within randomised controlled trials (RCTs). PURPOSE: The aim of this study is to describe the ways in which salivary diurnal cortisol has been measured within RCTs of health or behavioural interventions in adults. METHODS: Six electronic databases (up to May 21, 2015) were systematically searched for RCTs which used salivary diurnal cortisol as an outcome measure to evaluate health or behavioural interventions in adults. A narrative synthesis was undertaken of the findings in relation to salivary cortisol methodology and outcomes. RESULTS: From 78 studies that fulfilled the inclusion criteria, 30 included healthy participants (38.5 %), 27 included patients with physical disease (34.6 %) and 21 included patients with psychiatric disease (26.9 %). Psychological therapies were most commonly evaluated (n = 33, 42.3 %). There was substantial heterogeneity across studies in relation to saliva collection protocols and reported cortisol parameters. Only 39 studies (50 %) calculated a rhythm parameter such as the diurnal slope or the cortisol awakening response (CAR). Patterns of change in cortisol parameters were inconsistent both within and across studies and there was low agreement with clinical findings. CONCLUSIONS: Salivary diurnal cortisol is measured inconsistently across RCTs, which is limiting the interpretation of findings within and across studies. This indicates a need for more validation work, along with consensus guidelines. PMID- 27007277 TI - Manganese Oxidation State Assignment for Manganese Catalase. AB - The oxidation state assignment of the manganese ions present in the superoxidized manganese (III/IV) catalase active site is determined by comparing experimental and broken symmetry density functional theory calculated (14)N, (17)O, and (1)H hyperfine couplings. Experimental results have been interpreted to indicate that the substrate water is coordinated to the Mn(III) ion. However, by calculating hyperfine couplings for both scenarios we show that water is coordinated to the Mn(IV) ion and that the assigned oxidation states of the two manganese ions present in the site are the opposite of that previously proposed based on experimental measurements alone. PMID- 27007276 TI - ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro intestinal encephalomyopathy. AB - Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly. PMID- 27007279 TI - Safety profiles of first-line therapies for metastatic non-squamous non-small cell lung cancer. AB - INTRODUCTION: Lung cancer still represents the leading cause of death for cancer. About the 70% of diagnosis are in advanced-stage. Non-small-cell lung cancer (NSCLC) represents the 85% of all diagnosed lung cancers and non-squamous histology represents the 40% of all NSCLC. First-line therapies increase survival, control symptoms and improve quality of life, compared with best supportive care. It is crucial to choose a treatment with a low impact on patient's life considering the related toxicities. AREAS COVERED: Adverse events (AEs) of first-line therapies for non-squamous NSCLC are here reviewed and discussed, from evidences in clinical trials conducting to drugs approval. EXPERT OPINION: For advanced disease, palliation and preserving patients QoL are still the primary goal of treatment. Therefore, differing toxicity profiles are often a deciding factor in first-line and also maintenance setting for non-squamous NSCLC. Special attention is necessary to renal function and drugs' nephrotoxicity. Moreover, it is to consider the specific AEs of drugs classes: hypertension, bleeding, and proteinuria, for anti-VEGF therapy; skin toxicity, diarrhea, interstitial lung disease for TKIs; vision disorders, and hepatotoxicity for ALK-inhibitor. It is important to select patients for a treatment on the basis of their comorbidities and the presence of risk factors. PMID- 27007278 TI - Altered primary chromatin structures and their implications in cancer development. AB - BACKGROUND: Cancer development is a complex process involving both genetic and epigenetic changes. Genetic changes in oncogenes and tumor-suppressor genes are generally considered as primary causes, since these genes may directly regulate cellular growth. In addition, it has been found that changes in epigenetic factors, through mutation or altered gene expression, may contribute to cancer development. In the nucleus of eukaryotic cells DNA and histone proteins form a structure called chromatin which consists of nucleosomes that, like beads on a string, are aligned along the DNA strand. Modifications in chromatin structure are essential for cell type-specific activation or repression of gene transcription, as well as other processes such as DNA repair, DNA replication and chromosome segregation. Alterations in epigenetic factors involved in chromatin dynamics may accelerate cell cycle progression and, ultimately, result in malignant transformation. Abnormal expression of remodeler and modifier enzymes, as well as histone variants, may confer to cancer cells the ability to reprogram their genomes and to yield, maintain or exacerbate malignant hallmarks. At the end, genetic and epigenetic alterations that are encountered in cancer cells may culminate in chromatin changes that may, by altering the quantity and quality of gene expression, promote cancer development. METHODS: During the last decade a vast number of studies has uncovered epigenetic abnormalities that are associated with the (anomalous) packaging and remodeling of chromatin in cancer genomes. In this review I will focus on recently published work dealing with alterations in the primary structure of chromatin resulting from imprecise arrangements of nucleosomes along DNA, and its functional implications for cancer development. CONCLUSIONS: The primary chromatin structure is regulated by a variety of epigenetic mechanisms that may be deregulated through gene mutations and/or gene expression alterations. In recent years, it has become evident that changes in chromatin structure may coincide with the occurrence of cancer hallmarks. The functional interrelationships between such epigenetic alterations and cancer development are just becoming manifest and, therefore, the oncology community should continue to explore the molecular mechanisms governing the primary chromatin structure, both in normal and in cancer cells, in order to improve future approaches for cancer detection, prevention and therapy, as also for circumventing drug resistance. PMID- 27007281 TI - Effect of infection age on an SIS epidemic model on complex networks. AB - In this paper, based on an SIS model, we construct an epidemic model with infection age to investigate the disease transmission on complex networks. By analyzing the characteristic equations associated with the equilibria, we obtain the basic reproduction number [Formula: see text]. It is shown that if [Formula: see text] then the disease-free equilibrium is globally asymptotically stable while if [Formula: see text] then there is a unique endemic equilibrium, which is asymptotically stable. Our investigation indicates that if the maximal degree of the network is large enough then the endemic equilibrium always exists. Sensitivity analysis on the basic reproduction number [Formula: see text] in terms of the parameters is carried out to illustrate their effects on the disease transmission and to develop appropriate control strategies. PMID- 27007280 TI - Mathematical modeling of thrombus formation in idealized models of aortic dissection: initial findings and potential applications. AB - Aortic dissection is a major aortic catastrophe with a high morbidity and mortality risk caused by the formation of a tear in the aortic wall. The development of a second blood filled region defined as the "false lumen" causes highly disturbed flow patterns and creates local hemodynamic conditions likely to promote the formation of thrombus in the false lumen. Previous research has shown that patient prognosis is influenced by the level of thrombosis in the false lumen, with false lumen patency and partial thrombosis being associated with late complications and complete thrombosis of the false lumen having beneficial effects on patient outcomes. In this paper, a new hemodynamics-based model is proposed to predict the formation of thrombus in Type B dissection. Shear rates, fluid residence time, and platelet distribution are employed to evaluate the likelihood for thrombosis and to simulate the growth of thrombus and its effects on blood flow over time. The model is applied to different idealized aortic dissections to investigate the effect of geometric features on thrombus formation. Our results are in qualitative agreement with in-vivo observations, and show the potential applicability of such a modeling approach to predict the progression of aortic dissection in anatomically realistic geometries. PMID- 27007282 TI - Pregnancy-associated plasma protein-A promotes TF procoagulant activity in human endothelial cells by Akt-NF-kappaB axis. AB - Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a controversial role in pathophysiology of cardiovascular disease. It seems involved in progression of atherosclerosis and is widely represented in atherosclerotic plaque. PAPP-A plasma levels are elevated in patients with acute coronary syndromes (ACS), thus it has been suggested that it might be a prognostic marker for developing major cardiovascular events. However, the pathophysiological link(s) between PAPP-A and ACS are still unknown. Several studies have indicated that tissue factor (TF) plays a pivotal role in the pathophysiology of ACS by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates whether PAPP-A, at concentrations measurable in ACS patients, might induce TF expression in human endothelial cells in culture (HUVEC). In HUVEC, PAPP-A induced TF-mRNA transcription as demonstrated by real time PCR and expression of functionally active TF as demonstrated by FACS analysis and pro-coagulant activity assay. PAPP A induced TF expression through the activation of Akt/NF-kappaB axis, as demonstrated by luciferase assay and by suppression of TF-mRNA transcription as well as of TF expression/activity by Akt and NF-kappaB inhibitors. These data indicate that PAPP-A promotes TF expression in human endothelial cells and support the hypothesis that this proteinase, besides being involved in progression of atherosclerosis, does not represent an independent risk factor for adverse cardiovascular events, but it rather might play an "active" role in the pathophysiology of ACS as an effector molecule able to induce a pro-thrombotic phenotype in endothelial cells. PMID- 27007284 TI - Loneliness of oncology patients at the end of life. AB - BACKGROUND: Terminal stage cancer patients experience anxiety about death and pessimism about the future. They usually fear that as they approach death, their pain will increase, they will lose their reputation, and they will be alone. However, few studies have evaluated the loneliness that these cancer patients feel. This was a cross-sectional and definitive study that evaluated the feeling of loneliness in terminal cancer patients. METHODS: In total, 55 cancer patients with terminal cancer who were hospitalised for palliative therapy between 14 November 2014 and 14 January 2015 in the Okmeydani Training and Research Hospital were included in the study. The patients were given a questionnaire form that included sociodemographic properties and University of California Los Angeles Loneliness Scale to collect data. RESULTS: Loneliness was detected as 53.61 +/- 9.29. There was no relationship between sociodemographic data and loneliness (p > 0.05). Regression analysis revealed that family support and sharing of emotional stress were related to the level of loneliness (p < 0.05). More than half of the patients needed psychological support because they could not handle the situation. CONCLUSIONS: Terminal stage cancer patients felt lonely in general, and patients with a lack of visitors and family support experienced a higher level of loneliness. PMID- 27007283 TI - Interprofessional collaboration and integration as experienced by social workers in health care. AB - Interprofessional collaboration in health care is gaining popularity. This secondary analysis focuses on social workers' experiences on interprofessional teams. The data revealed that social workers perceived overall collaboration as positive. However, concerns were made apparent regarding not having the opportunity to work to full scope and a lack of understanding of social work ideology from other professionals. Both factors seem to impede integration of and collaboration with social workers on health care teams. This study confirms the need to encourage and support health care providers to more fully understand the foundation, role, and efficacy of social work on interprofessional teams. PMID- 27007285 TI - Granular cell tumor in two oral anatomic sites. AB - Granular cell tumor (GCT) is an uncommon benign soft tissue neoplasm, which usually presents as a solitary nodule, appearing especially in the tongue. There are few cases of multiple oral GCT in the English-language literature, with only three cases reported in the last 20 years. This report describes a case of two oral GCT in a young patient and provides a literature review from 1995 to 2015. Clinical characteristics of the reviewed cases were retrieved and compared with the present case. Exceptionally, the current case was the only one that occurred in an adolescent and solely affected the oral cavity. Besides the oral cavity, the other cases also observed GCT lesions in the skin. Although rare, it is important to know multiple oral GCT clinical and histopathological characteristics so they can be correctly diagnosed, treated and followed up. PMID- 27007287 TI - Micro- and Nanoscale Energetic Materials as Effective Heat Energy Sources for Enhanced Gas Generators. AB - In this study, we systematically investigated the effect of micro- and nanoscale energetic materials in formulations of aluminum microparticles (Al MPs; heat source)/aluminum nanoparticles (Al NPs; heat source)/copper oxide nanoparticles (CuO NPs; oxidizer) on the combustion and gas-generating properties of sodium azide microparticles (NaN3 MPs; gas-generating agent) for potential applications in gas generators. The burn rate of the NaN3 MP/CuO NP composite powder was only ~0.3 m/s. However, the addition of Al MPs and Al NPs to the NaN3 MP/CuO NP matrix caused the rates to reach ~1.5 and ~5.3 m/s, respectively. In addition, the N2 gas volume flow rate generated by the ignition of the NaN3 MP/CuO NP composite powder was only ~0.6 L/s, which was significantly increased to ~1.4 and ~3.9 L/s by adding Al MPs and Al NPs, respectively, to the NaN3 MP/CuO NP composite powder. This suggested that the highly reactive Al MPs and NPs, with the assistance of CuO NPs, were effective heat-generating sources enabling the complete thermal decomposition of NaN3 MPs upon ignition. Al NPs were more effective than Al MPs in the gas generators because of the increased reactivity induced by the reduced particle size. Finally, we successfully demonstrated that a homemade airbag with a specific volume of ~140 mL could be rapidly and fully inflated by the thermal activation of nanoscale energetic material-added gas generating agents (i.e., NaN3 MP/Al NP/CuO NP composites) within the standard time of ~50 ms for airbag inflation. PMID- 27007286 TI - The Carina(c) middle ear implant: surgical and functional outcomes. AB - The Carina(c) system (Cochlear Ltd, Sydney, Australia) is a totally implantable prosthesis designed to meet the needs of acoustic amplification in adults with moderate-to-severe sensorineural or mixed hearing loss. It mechanically stimulates the ossicles or labyrinthine windows. The object of this study was to update surgical and functional results obtained in a consistent sample of Carina(c) recipients. The data sheets of 26 patients who underwent Carina(c) surgery at two ENT units [i.e., ENT Audiology and Phoniatrics Unit of the University Hospital of Pisa (Pisa, Italy) and ENT Unit of "Guglielmo da Saliceto" Hospital of Piacenza (Piacenza, Italy)] were evaluated for the surgical and audiological outcomes. Twenty patients received a unilateral device, whereas six patients were bilaterally implanted (simultaneously in one patient and sequentially in the remaining five patients). The total number of ears implanted in this study was 32. Most implanted patients expressed a high degree of satisfaction with the prosthesis, which highlights the improvement in hearing in different environmental conditions, the cosmetic advantages, and greater freedom in performing common activities in daily living. Audiological examination demonstrated valid functional gain and significant improvement in speech perception in quiet. Based on this experience, the Carina(c) is a valid alternative to hearing aids. Moreover, a bilateral implantation, even a simultaneous implantation, is a viable option for selected motivated patients because the intervention is generally well tolerated and the surgery time is relatively fast. PMID- 27007288 TI - Cinemeducation in GP training. PMID- 27007290 TI - Hydrogeochemical and isotopic tracers for identification of seasonal and long term over-exploitation of the Pleistocene thermal waters. AB - The aim of the study was to develop and test an optimal and cost-effective regional quality monitoring system in depleted transboundary low-temperature Neogene geothermal aquifers in the west Pannonian basin. Potential tracers for identification of seasonal and long-term quality changes of the Pleistocene thermal waters were investigated at four multiple-screened wells some 720 to 1570 m deep in Slovenia. These thermal waters are of great balneological value owing to their curative effects and were sampled monthly between February 2014 and January 2015. Linear correlation and regression analyses, ANOVA and Kolmogorov Smirnov two-sample test for two independent samples were used to determine their seasonal and long-term differences. Temperature, pH, electrical conductivity, redox potential and dissolved oxygen did not identify varying inflow conditions; however, they provided sufficient information to distinguish between the four end members. Characteristic (sodium) and conservative (chloride) tracers outlined long-term trends in changes in quality but could not differentiate between the seasons. Stable isotopes of delta (18)O and delta (2)H were used to identify sequential monthly and long-term trends, and origin and mixing of waters, but failed to distinguish the difference between the seasons. A new local paleo meteoric water line (delta (2)H = 9.2*delta (18)O + 26.3) was outlined for the active regional groundwater flow system in the Pannonian to Pliocene loose sandstone and gravel. A new regression line (delta (2)H = 2.3*delta (18)O-45.2) was calculated for thermomineral water from the more isolated Badenian to Lower Pannonian turbiditic sandstone, indicating dilution of formation water. Water composition was generally stable over the 1-year period, but long-term trends indicate that changes in quality occur, implying deterioration of the aquifers status. PMID- 27007289 TI - Natural attenuation of toxic metal phytoavailability in 35-year-old sewage sludge amended soil. AB - Toxic heavy metals persist in agricultural soils and ecosystem for many decades after their application as contaminants in sewage sludge and fertilizer products This study assessed the potential long-term risk of cadmium (Cd), lead (Pb), zinc (Zn), and copper (Cu) in land-applied sewage sludge to food crop contamination. A sewage sludge-amended soil (SAS) aged in the field more than 35 years was used in a greenhouse pot experiment with leafy vegetables (lettuce and amaranth) having strong Cd and Zn accumulation tendencies. Soil media with variable levels of available Cd, Zn, and Cu (measured using 0.01 M CaCl2 extraction) were prepared by diluting SAS with several levels of uncontaminated control soil. Despite long term aging in the field, the sludge site soil still retains large reserves of heavy metals, residual organic matter, phosphorus, and other nutrients, but its characteristics appear to have stabilized over time. Nevertheless, lettuce and amaranth harvested from the sludge-treated soil had undesirable contents of Cd and Zn. The high plant uptake efficiency for Cd and Zn raises a concern regarding the quality and safety of leafy vegetables in particular, when these crops are grown on soils that have been amended heavily with sewage sludge products at any time in their past. PMID- 27007291 TI - Bioaccumulation of metals in common carp (Cyprinus carpio L.) from water bodies of Anatolia (Turkey): a review with implications for fisheries and human food consumption. AB - Although fish is widely consumed by humans for its nutritional properties, accumulation of heavy metals can pose serious health hazards. Widespread common carp Cyprinus carpio is cultured worldwide and represents an economically important species for fisheries in several countries. These include Turkey, where C. carpio often makes for a large part of the sales of the locally marketed fish and also for a traditional dish. This study provides a review of bioaccumulation of metals in tissues of C. carpio from water bodies of Anatolia and also includes reference to worldwide studies. From 42 water bodies across the region, 27 metals in total were studied, of which Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were the most widely analysed, mainly in the muscle, liver and gill tissues. Amongst the potentially toxic metals, Cd, Cr and Pb occurred in several water bodies at concentrations not only above maximum allowed limits but also higher relative to other water bodies worldwide, even though As, Hg and Ni were also sometimes present at potentially hazardous concentrations. The essential metals Cu, Fe, Mn, Se and Zn were detected at various concentrations, with the latter two occasionally above limit. All water bodies flagged as having especially critical (i.e. above limit) concentrations of toxic metals supported C. carpio fisheries from highly populated regions, raising concern about food safety and calling for preventative measures. Given the significantly lower bioaccumulation levels in the muscle relative to the liver and gill tissues, it is suggested that consumption of C. carpio as fillets may be safer than after processing into e.g. meat balls and sausages. The limits of 1.0 MUg/g for Cr and 1.15 MUg/g for Se, currently lacking from the Turkish food safety legislation, are proposed, and it is suggested that a similar meta-analytical approach as adopted in this study may benefit other countries where C. carpio represents an important fisheries resource. PMID- 27007293 TI - Concurrent Modeling of Hydrodynamics and Interaction Forces Improves Particle Deposition Predictions. AB - It is widely believed that media surface roughness enhances particle deposition numerous, but inconsistent, examples of this effect have been reported. Here, a new mathematical framework describing the effects of hydrodynamics and interaction forces on particle deposition on rough spherical collectors in absence of an energy barrier was developed and validated. In addition to quantifying DLVO force, the model includes improved descriptions of flow field profiles and hydrodynamic retardation functions. This work demonstrates that hydrodynamic effects can significantly alter particle deposition relative to expectations when only the DLVO force is considered. Moreover, the combined effects of hydrodynamics and interaction forces on particle deposition on rough, spherical media are not additive, but synergistic. Notably, the developed model's particle deposition predictions are in closer agreement with experimental observations than those from current models, demonstrating the importance of inclusion of roughness impacts in particle deposition description/simulation. Consideration of hydrodynamic contributions to particle deposition may help to explain discrepancies between model-based expectations and experimental outcomes and improve descriptions of particle deposition during physicochemical filtration in systems with nonsmooth collector surfaces. PMID- 27007292 TI - Discovery, Optimization, and Biological Evaluation of Sulfonamidoacetamides as an Inducer of Axon Regeneration. AB - Axon regeneration after injury in the central nervous system is hampered in part because if an age-dependent decline in the intrinsic axon growth potential, and one of the strategies to stimulate axon growth in injured neurons involves pharmacological manipulation of implicated signaling pathways. Here we report phenotypic cell-based screen of chemical libraries and structure-activity-guided optimization that resulted in the identification of compound 7p which promotes neurite outgrowth of cultured primary neurons derived from the hippocampus, cerebral cortex, and retina. In an animal model of optic nerve injury, compound 7p was shown to induce growth of GAP-43 positive axons, indicating that the in vitro neurite outgrowth activity of compound 7p translates into stimulation of axon regeneration in vivo. Further optimization of compound 7p and elucidation of the mechanisms by which it elicits axon regeneration in vivo will provide a rational basis for future efforts to enhance treatment strategies. PMID- 27007294 TI - Lack of cooperation between physicians and dentists during osteoporosis treatment may increase fractures and osteonecrosis of the jaw. AB - OBJECTIVE: Our previous questionnaire-based survey suggested that discontinuation of antiresorptive agents before tooth extraction may increase adverse events and disturb osteoporosis treatment without completely preventing osteonecrosis of the jaw (O.N.J.). We also found little cooperation between physicians and dentists in Japan. However, limitations of our previous study included a survey of doctors belonging to small clinics and a small sample size. Our current study aimed to confirm the results of our previous survey in doctors mainly belonging to academia. METHODS: A structured questionnaire including 14 key clinical queries was sent to 1812 physicians of the Japan Osteoporosis Society, and 629 responses were received. RESULTS: Dentists requested discontinuation of many medications that were not associated with the incidence of O.N.J. A total of 523 respondents had received discontinuation requests from dentists. Of these, 97 respondents experienced 119 adverse events including 25 fractures and seven incidences of O.N.J. The ratios of valid responses for fractures were 3.6% and 5.3% in patients with a discontinuation of <3 and >=3 months, respectively. Those for O.N.J. were 0.7% and 1.6%, respectively. Respondents who refused discontinuation requests reported no cases of O.N.J. Approximately 17% of respondents had patients who discontinued osteoporosis treatment following a requested drug discontinuation after tooth extraction. Approximately 62% of respondents did not request oral health care by a dentist before antiresorptive therapy, and 72% reported no cooperation between physicians and dentists in their region. CONCLUSIONS: This study reconfirms the results of our previous survey. Discontinuation of antiresorptive treatment may increase both fractures and O.N.J. Immediate development of a strategy for sharing information about O.N.J. among physicians, dentists, and patients is required to reduce the incidence of both O.N.J. and skeletal events in osteoporosis treatment. Study limitations were selection bias due to low response rate and possible inaccurate responses to the questionnaire. PMID- 27007295 TI - Highly Flexible and High-Performance Complementary Inverters of Large-Area Transition Metal Dichalcogenide Monolayers. AB - Complementary inverters constructed from large-area monolayers of WSe2 and MoS2 achieve excellent logic swings and yield an extremely high gain, large total noise margin, low power consumption, and good switching speed. Moreover, the WSe2 complementary-like inverters built on plastic substrates exhibit high mechanical stability. The results provide a path toward large-area flexible electronics. PMID- 27007297 TI - Characterisation and evaluation of soft elastomeric actuators for hand assistive and rehabilitation applications. AB - Various hand exoskeletons have been proposed for the purposes of providing assistance in activities of daily living and rehabilitation exercises. However, traditional exoskeletons are made of rigid components that impede the natural movement of joints and cause discomfort to the user. This paper evaluated a soft wearable exoskeleton using soft elastomeric actuators. The actuators could generate the desired actuation of the finger joints with a simple design. The actuators were characterised in terms of their radius of curvature and force output during actuation. Additionally, the device was evaluated on five healthy subjects in terms of its assisted finger joint range of motion. Results demonstrated that the subjects were able to perform the grasping actions with the assistance of the device and the range of motion of individual finger joints varied from subject to subject. This work evaluated the performance of a soft wearable exoskeleton and highlighted the importance of customisability of the device. It demonstrated the possibility of replacing traditional rigid exoskeletons with soft exoskeletons that are more wearable and customisable. PMID- 27007296 TI - Disrupted ADP-ribose metabolism with nuclear Poly (ADP-ribose) accumulation leads to different cell death pathways in presence of hydrogen peroxide in procyclic Trypanosoma brucei. AB - BACKGROUND: Poly(ADP-ribose) (PAR) metabolism participates in several biological processes such as DNA damage signaling and repair, which is a thoroughly studied function. PAR is synthesized by Poly(ADP-ribose) polymerase (PARP) and hydrolyzed by Poly(ADP-ribose) glycohydrolase (PARG). In contrast to human and other higher eukaryotes, Trypanosoma brucei contains only one PARP and PARG. Up to date, the function of these enzymes has remained elusive in this parasite. The aim of this work is to unravel the role that PAR plays in genotoxic stress response. METHODS: The optimal conditions for the activity of purified recombinant TbPARP were determined by using a fluorometric activity assay followed by screening of PARP inhibitors. Sensitivity to a genotoxic agent, H2O2, was assessed by counting motile parasites over the total number in a Neubauer chamber, in presence of a potent PARP inhibitor as well as in procyclic transgenic lines which either down regulate PARP or PARG, or over-express PARP. Triplicates were carried out for each condition tested and data significance was assessed with two-way Anova followed by Bonferroni test. Finally, PAR influence was studied in cell death pathways by flow cytometry. RESULTS: Abolition of a functional PARP either by using potent inhibitors present or in PARP-silenced parasites had no effect on parasite growth in culture; however, PARP-inhibited and PARP down-regulated parasites presented an increased resistance against H2O2 treatment when compared to their wild type counterparts. PARP over-expressing and PARG-silenced parasites displayed polymer accumulation in the nucleus and, as expected, showed diminished resistance when exposed to the same genotoxic stimulus. Indeed, they suffered a necrotic death pathway, while an apoptosis-like mechanism was observed in control cultures. Surprisingly, PARP migrated to the nucleus and synthesized PAR only after a genomic stress in wild type parasites while PARG occurred always in this organelle. CONCLUSIONS: PARP over-expressing and PARG-silenced cells presented PAR accumulation in the nucleus, even in absence of oxidative stress. Procyclic death pathway after genotoxic damage depends on basal nuclear PAR. This evidence demonstrates that the polymer may have a toxic action by itself since the consequences of an exacerbated PARP activity cannot fully explain the increment in sensitivity observed here. Moreover, the unusual localization of PARP and PARG would reveal a novel regulatory mechanism, making them invaluable model systems. PMID- 27007298 TI - Innate Host Habitat Preference in the Parasitoid Diachasmimorpha longicaudata: Functional Significance and Modifications through Learning. AB - Parasitoids searching for polyphagous herbivores can find their hosts in a variety of habitats. Under this scenario, chemical cues from the host habitat (not related to the host) represent poor indicators of host location. Hence, it is unlikely that naive females show a strong response to host habitat cues, which would become important only if the parasitoids learn to associate such cues to the host presence. This concept does not consider that habitats can vary in profitability or host nutritional quality, which according to the optimal foraging theory and the preference-performance hypothesis (respectively) could shape the way in which parasitoids make use of chemical cues from the host habitat. We assessed innate preference in the fruit fly parasitoid Diachasmimorpha longicaudata among chemical cues from four host habitats (apple, fig, orange and peach) using a Y-tube olfactometer. Contrary to what was predicted, we found a hierarchic pattern of preference. The parasitism rate realized on these fruit species and the weight of the host correlates positively, to some extent, with the preference pattern, whereas preference did not correlate with survival and fecundity of the progeny. As expected for a parasitoid foraging for generalist hosts, habitat preference changed markedly depending on their previous experience and the abundance of hosts. These findings suggest that the pattern of preference for host habitats is attributable to differences in encounter rate and host quality. Host habitat preference seems to be, however, quite plastic and easily modified according to the information obtained during foraging. PMID- 27007299 TI - An engineering viewpoint on biological robustness. AB - In his splendid article "Can a biologist fix a radio?--or, what I learned while studying apoptosis," Y. Lazebnik argues that when one uses the right tools, similarity between a biological system, like a signal transduction pathway, and an engineered system, like a radio, may not seem so superficial. Here I advance this idea by focusing on the notion of robustness as a unifying lens through which to view complexity in biological and engineered systems. I show that electronic amplifiers and gene expression circuits share remarkable similarities in their dynamics and robustness properties. I explore robustness features and limitations in biology and engineering and highlight the role of negative feedback in shaping both. PMID- 27007300 TI - Effects of an energy balance educational intervention and the COPE cognitive behavioral therapy intervention for Division I U.S. Air Force Academy female athletes. AB - BACKGROUND AND PURPOSE: Female athletes struggle harder than male athletes to lose body fat and maintain a leaner physique. The purpose of this study was to determine the effects of an educational and cognitive behavioral therapy (CBT) based intervention on knowledge, body composition, anxiety, stress, and nutritional intake. METHODS: A randomized controlled trial was conducted with 153 female athletes from the U.S. Air Force Academy (USAFA). Participants were assigned to one of three groups: (a) a combined energy balance and CBT-based intervention (E1); (b) a CBT-based intervention alone (E2); and (c) a control group (C). Main outcomes included a DXA scan for body composition, a knowledge test, the GAD-7 for anxiety, the brief inventory of perceived stress (BIPS) for stress, and a 24-h food recall. FINDINGS: Significant improvement on knowledge of energy balance occurred in all three groups E1 (p < .001), E2, and C (p < .05). Significant reductions in percentage of body fat occurred in E1 (p < .001) and E2 (p < .05). There also were significant reductions in the percent of fat consumed by E1 (p < .05) and saturated fat consumed by both E1 and E2 (p < .05). The control group only demonstrated a significant increase in stress as measured by the BIPS (p < .05). CONCLUSIONS: A combined energy balance and CBT-based intervention improves knowledge and body fat. IMPLICATIONS: The importance to assess knowledge, anxiety, stress, nutrition intake, and percentage of body fat in female athletes and to deliver evidence-based interventions to improve their health outcomes. PMID- 27007301 TI - Facile Synthesis of Fe2O3 Nano-Dots@Nitrogen-Doped Graphene for Supercapacitor Electrode with Ultralong Cycle Life in KOH Electrolyte. AB - Fe2O3 nanodots supported on nitrogen-doped graphene sheets (denoted as Fe2O3 NDs@NG) with different loading masses are prepared through a facile one-pot solvothermal method. The resulting Fe2O3 NDs@NG composites exhibit outstanding electrochemical properties in aqueous KOH electrolyte. Among them, with the optimal loading mass of Fe2O3 NDs, the corresponding Fe2O3 NDs@NG-0.75 sample is able to deliver a high specific capacitance of 274 F g(-1) at 1 A g(-1) and the capacitance is still as high as 140 F g(-1) even at a ultrahigh current density of 50 A g(-1), indicating excellent rate capability. More remarkably, it displays superior capacitance retention after 100,000 cycles (about 75.3% at 5 A g(-1)), providing the best reported long-term cycling stability for iron oxides in alkaline electrolytes to date. Such excellent electrochemical performance is attributed to the right combination of highly dispersed Fe2O3 NDs and appropriately nitrogen-doped graphene sheets, which enable the Fe2O3 NDs@NG-0.75 to offer plenty of accessible redox active sites, facilitate the electron transfer and electrolyte diffusion, as well as effectively alleviate the volume change of Fe2O3 NDs during the charge-discharge process. PMID- 27007302 TI - Efficacy of Two Radiologic-Assisted Prophylactic Gastropexy Techniques. AB - OBJECTIVE: To describe the technique and clinical outcome of prophylactic percutaneous radiologic-assisted gastropexy (PRG) and radiologic-assisted incisional gastropexy (RIG) in client-owned dogs. STUDY DESIGN: Prospective, nonrandomized clinical trial. ANIMALS: Fourteen client-owned, large, and giant breed dogs. METHODS: Four dogs underwent PRG with fluoroscopic guidance to place 2 T-fasteners into the pyloric antrum and secure it to the right body wall. Ten dogs underwent RIG, which was a modification of PRG. For RIG, the T-fasteners were first used to approximate the pyloric antrum and body wall, then a full thickness incision through the body wall was made and the pyloric antrum was sutured to the internal abdominal wall. The duration and complications of each procedure were recorded. The gastropexy was assessed by abdominal ultrasound at day 1, week 2, and week 8 postoperative and by barium gastrogram at week 8 postoperative. RESULTS: No dogs undergoing PRG had a gastropexy present at week 2. All dogs undergoing RIG had ultrasonographic evidence of gastropexy at day 1, week 2, and week 8 postoperative. Gastrograms in 9/9 dogs were consistent with an intact gastropexy, appropriate gastric positioning and appropriate gastric emptying began. No major complications were noted. CONCLUSION: The PRG was unsatisfactory and did not result in a permanent gastropexy. The RIG was safe and created a gastropexy that remained intact at 8 weeks postoperative. The RIG should be considered as a minimally invasive option for prophylactic gastropexy in dogs of at-risk breeds. PMID- 27007303 TI - Rationally Designed 3D Fe and N Codoped Graphene with Superior Electrocatalytic Activity toward Oxygen Reduction. AB - Pyrolyzing Fe- and N-contained precursor together or separately with graphene results in codoped graphene dominated by bonded or separated Fe and N configuration, respectively. While the Fe?N bonded case greatly enhances activity toward oxygen reduction, the separated one does not. This rationally designed Fe and N codoped 3D graphene exhibits superior electrocatalytic activity than the state-of-the-art Pt/C catalyst. PMID- 27007304 TI - 2015 and human cancer: back to overall survival. PMID- 27007306 TI - Resource translocation drives delta(13) C fractionation during recovery from disturbance in giant kelp, Macrocystis pyrifera. AB - Resource allocation and translocation are fundamental physiological functions for autotrophs. The mobilization and use of resources drive population dynamics by regulating growth and recovery of individuals, but also influences ecosystem level processes such as primary productivity and carbon cycling. This study provides the first observation of translocation-driven gradients of delta(13) C in macroalgae, a critically important phenomenon recognized in vascular plants for decades. A ~100/00 delta(13) C increase in new giant kelp (Macrocystis pyrifera) fronds relative to mature canopy blades was produced after 5 weeks following a biomass removal experiment, more than twice the variation typical for macroalgae. The observed delta(13) C patterns are consistent with tissue enrichment following resource translocation in vascular plants. The analogous source-sink relationships and consistent translocation patterns in Macrocystis and vascular plants suggest that translocation of stored resources is critical for structuring productivity and recovery from disturbance in important, habitat forming macroalgae such as kelps and fucoids. PMID- 27007305 TI - Salt effects on functional traits in model and in economically important Lotus species. AB - A common stress on plants is NaCl-derived soil salinity. Genus Lotus comprises model and economically important species, which have been studied regarding physiological responses to salinity. Leaf area ratio (LAR), root length ratio (RLR) and their components, specific leaf area (SLA) and leaf mass fraction (LMF) and specific root length (SRL) and root mass fraction (RMF) might be affected by high soil salinity. We characterised L. tenuis, L. corniculatus, L. filicaulis, L. creticus, L. burtii and L. japonicus grown under different salt concentrations (0, 50, 100 and 150 mm NaCl) on the basis of SLA, LMF, SRL and RMF using PCA. We also assessed effects of different salt concentrations on LAR and RLR in each species, and explored whether changes in these traits provide fitness benefit. Salinity (150 mm NaCl) increased LAR in L. burtii and L. corniculatus, but not in the remaining species. The highest salt concentration caused a decrease of RLR in L. japonicus Gifu, but not in the remaining species. Changes in LAR and RLR would not be adaptive, according to adaptiveness analysis, with the exception of SLA changes in L. corniculatus. PCA revealed that under favourable conditions plants optimise surfaces for light and nutrient acquisition (SLA and SRL), whereas at higher salt concentrations they favour carbon allocation to leaves and roots (LMF and RMF) in detriment to their surfaces. PCA also showed that L. creticus subjected to saline treatment was distinguished from the remaining Lotus species. We suggest that augmented carbon partitioning to leaves and roots could constitute a salt-alleviating mechanism through toxic ion dilution. PMID- 27007307 TI - Getting a grip on genetic modification in brown algae. PMID- 27007308 TI - Gene silencing in Fucus embryos: developmental consequences of RNAi-mediated cytoskeletal disruption. AB - Brown algae (Phaeophyceae) are an important algal class that play a range of key ecological roles. They are often important components of rocky shore communities. A number of members of the Fucales and Ectocarpales have provided models for the study of multicellular evolution, reproductive biology and polarized development. Indeed the fucoid algae exhibit the unusual feature of inducible embryo polarization, allowing many classical studies of polarity induction. The potential of further studies of brown algae in these important areas has been increasingly hindered by the absence of tools for manipulation of gene expression that would facilitate further mechanistic analysis and gene function studies at a molecular level. The aim of this study was to establish a method that would allow the analysis of gene function through RNAi-mediated gene knockdown. We show that injection of double-stranded RNA (dsRNA) corresponding to an alpha-tubulin gene into Fucus serratus Linnaeus zygotes induces the loss of a large proportion of the microtubule cytoskeleton, leading to growth arrest and disruption of cell division. Injection of dsRNA targeting beta-actin led to reduced rhizoid growth, enlarged cells and the failure to develop apical hair cells. The silencing effect on actin expression was maintained for 3 months. These results indicate that the Fucus embryo possesses a functional RNA interference system that can be exploited to investigate gene function during embryogenesis. PMID- 27007309 TI - Morphology of the crustose coralline alga Pseudolithophyllum muricatum (Corallinales, Rhodophyta) responds to 30 years of ocean acidification in the Northeast Pacific. AB - As the process of ocean acidification alters seawater carbon chemistry, physiological processes such as skeletal accretion are expected to become more difficult for calcifying organisms. The crustose coralline red algae (Corallinales, Rhodophyta) form an important guild of calcifying primary producers in the temperate Northeast Pacific. The morphology of important ecological traits, namely, skeletal density and thallus thickness near the growing edge, was evaluated in Pseudolithophyllum muricatum (Foslie) Steneck & R.T. Paine, the competitively dominant alga within this guild. P. muricatum shows a morphological response to increased ocean acidification in the temperate Northeast Pacific. Comparing historical (1981-1997) and modern (2012) samples from the field, crust thickness near the growing edge was approximately half as thick in modern samples compared with historical samples, while crust calcite density showed no significant change between the two sample groups. Morphological changes at the growing edge have important consequences for mediating competitive interactions within this guild of algae, and may affect the role of crustose coralline algal beds as hosts to infaunal communities and facilitators of recruitment in many invertebrate and macroalgal species. PMID- 27007310 TI - Functional group richness: implications of biodiversity for light use and lipid yield in microalgae. AB - Currently, very few studies address the relationship between diversity and biomass/lipid production in primary producer communities for biofuel production. Basic studies on the growth of microalgal communities, however, provide evidence of a positive relationship between diversity and biomass production. Recent studies have also shown that positive diversity-productivity relationships are related to an increase in the efficiency of light use by diverse microalgal communities. Here, we hypothesize that there is a relationship between diversity, light use, and microalgal lipid production in phytoplankton communities. Microalgae from all major freshwater algal groups were cultivated in treatments that differed in species richness and functional group richness. Polycultures with high functional group richness showed more efficient light use and higher algal lipid content with increasing species richness. There was a clear correlation between light use and lipid production in functionally diverse communities. Hence, a powerful and cost-effective way to improve biofuel production might be accomplished by incorporating diversity related, resource-use dynamics into algal biomass production. PMID- 27007311 TI - Cyst-theca relationship of the arctic dinoflagellate cyst Islandinium minutum (Dinophyceae) and phylogenetic position based on SSU rDNA and LSU rDNA. AB - Round brown spiny cysts constitute a morphological group common in high latitude dinoflagellate cyst assemblages. The dinoflagellate cyst Islandinium minutum (Harland et Reid) Head, Harland et Matthiessen is the main paleoecological indicator of seasonal sea-ice cover in the Arctic. Despite the importance of this cyst in paleoceanographical studies, its biological affinity has so far been unknown. The biological affinity of the species I. minutum and its phylogenetic position based on the small subunit ribosomal RNA gene (SSU rDNA) and the large subunit ribosomal RNA gene (LSU rDNA) were established from cyst incubation experiments in controlled conditions, optical and scanning electron microscopy, and single-cell PCR. The thecal motile cell obtained was undescribed. Although the motile cell was similar to Archaeperidinium minutum (Kofoid) Jorgensen, the motile cell of I. minutum lacked a transitional plate in the cingular series, which is present in Archaeperidinium spp. Islandinium minutum and Archaeperidinium spp. were paraphyletic in all phylogenetic analyses. Furthermore, Protoperidinium tricingulatum, which also lacks a transitional plate, was closely related to I. minutum and transfered to the genus Islandinium. Based on available data, it is clear that Islandinium is distinct from Archaeperidinium. Therefore, we considered Islandinium Head, Harland et Matthiessen as a non-fossil genus and emend its description, as well as the species I. minutum. This is the first description of a cyst-theca relationship and the first study that reports molecular data based on SSU rDNA and LSU rDNA on a species assigned to the genus Islandinium. PMID- 27007312 TI - Survival in low light: photosynthesis and growth of a red alga in relation to measured in situ irradiance. AB - Reduced light availability for benthic primary producers as a result of anthropogenic activities may be an important driver of change in coastal seas. However, our knowledge of the minimum light requirements for benthic macroalgae limits our understanding of how these changes may affect primary productivity and the functioning of coastal ecosystems. This knowledge gap is particularly acute in deeper water, where the impacts of increased light attenuation will be most severe. We examined the minimum light requirements of Anotrichium crinitum, which dominates near the maximum depth limit for macroalgae throughout New Zealand and Southern Australia, and is a functional analog of rhodophyte macroalgae in temperate low-light (deep-water) habitats throughout the world. These data show that A. crinitum is a shade-adapted seaweed with modest light requirements for the initiation of net photosynthesis (1.49-2.25 MUmol photons . m(-2) . s(-1) ) and growth (0.12-0.19 mol photons . m(-2) . d(-1) ). A. crinitum maintains high photosynthetic efficiency and pigment content and a low C:N ratio throughout the year and can maintain biomass under sub-compensation (critical) light levels for at least 5 d. Nevertheless, in situ photon flux is less than the minimum light requirement for A. crinitum on at least 103 d per annum and is rarely sufficient to saturate growth. These findings reinforce the importance of understanding the physiological response of macroalgae at the extremes of environmental gradients and highlight the need to establish minimum thresholds that modification of the subtidal light environment should not cross. PMID- 27007313 TI - Phylogenetic distribution of compatible solute synthesis genes support a freshwater origin for cyanobacteria. AB - Previous work using ancestral state reconstruction of habitat salinity preference proposed that the early cyanobacteria likely lived in a freshwater environment. The aim of this study was to test that hypothesis by performing phylogenetic analyses of the genes underlying salinity preferences in the cyanobacteria. Phylogenetic analysis of compatible solute genes shows that sucrose synthesis genes were likely ancestral in the cyanobacteria, and were also likely inherited during the cyanobacterial endosymbiosis and into the photosynthetic algae and land plants. In addition, the genes for the synthesis of compatible solutes that are necessary for survival in marine and hypersaline environments (such as glucosylglycerol, glucosylglycerate, and glycine betaine) were likely acquired independently high up (i.e., more recently) in the cyanobacterial tree. Because sucrose synthesis is strongly associated with growth in a low salinity environment, this independently supports a freshwater origin for the cyanobacteria. It is also consistent with geologic evidence showing that the early oceans were much warmer and saltier than modern oceans-sucrose synthesis alone would have been insufficient for early cyanobacteria to have colonized early Precambrian oceans that had a higher ionic strength. Indeed, the acquisition of an expanded set of new compatible solute genes may have enabled the historical colonization of marine and hypersaline environments by cyanobacteria, midway through their evolutionary history. PMID- 27007314 TI - The effects of mysid grazing on kelp zoospore survival and settlement. AB - Recent studies have indicated that long-distance dispersal by kelp zoospores may play an important role in the colonization of newly exposed rocky habitats and in the recovery of recently disturbed kelp forests. This may be facilitated by the vertical transport of zoospores into the shallower portions of the water column where they are exposed to greater alongshore currents that increase their dispersal potential. However, this vertical transport can also expose them to elevated irradiances and enhanced grazing by zooplankton, both of which negatively impact zoospore survival and settlement. In this study, we used plankton tows to show that zooplankton (mysids) were at least seven times more abundant in the surface waters than near the benthos along the edge of a large kelp forest at the time of our spring sampling. We then used feeding experiments and epifluorescence microscopy to verify that these mysids grazed on kelp zoospores. Finally, we conducted laboratory experiments to show that grazing by these mysids over a 12 h period reduced kelp zoospore settlement by at least 50% relative to treatments without grazing. Together with previous studies that have revealed the impacts of high irradiance on zoospore survival and settlement, our study indicates that the vertical transport of kelp zoospores into the shallower portions of the water can also expose them to significantly increased mortality from mysid grazing. Thus, if these patterns are consistent over broader temporal and geographic scales, vertical transport may not be a viable method for sustained long-distance zoospore dispersal. PMID- 27007315 TI - Three novel species in the Pseudo-nitzschia pseudodelicatissima complex: P. batesiana sp. nov., P. lundholmiae sp. nov., and P. fukuyoi sp. nov. (Bacillariophyceae) from the Strait of Malacca, Malaysia. AB - A study on the morphology and phylogeny of 18 strains of Pseudo-nitzschia established from the Strait of Malacca, Peninsular Malaysia, was undertaken. Morphological data combined with molecular evidence show that they constitute three new species, for which the names, P. batesiana sp. nov., P. lundholmiae sp. nov., and P. fukuyoi sp. nov., are proposed. The three new species closely resemble species in the P. pseudodelicatissima complex sensu lato. Morphologically, P. batesiana differs from other species in the complex by having a smaller part of cell overlapping in the chain, whereas P. lundholmiae differs by having fewer poroid sectors and P. fukuyoi by having a distinct type of poroid sectors. Nucleotide sequences of the LSU rDNA (D1-D3) of the three new species reveal significant nucleotide sequence divergence (0.1%-9.3%) from each other and from other species in the P. pseudodelicatissima complex s.l. The three species are phylogenetically closely related to species in the P. pseudodelicatissima complex, with P. batesiana appearing as a sister taxon to P. circumpora, P. caciantha, and P. subpacifica; whereas P. lundholmiae and P. fukuyoi are more closely related to P. pseudodelicatissima and P. cuspidata. The three species show 2-3 compensatory base changes (CBCs) in their ITS2 transcripts when compared to the closely related species. The ITS2 with its structural information has proven its robustness in constructing a better resolved phylogenetic framework for Pseudo-nitzschia. PMID- 27007316 TI - A reappraisal of the genus Leptocylindrus (Bacillariophyta), with the addition of three species and the erection of Tenuicylindrus gen. nov. AB - Centric diatoms of the genus Leptocylindrus are common in the marine plankton worldwide. Only two species, L. danicus Cleve and L. minimus Gran, so far clearly belong to this genus, whose diversity has not been fully investigated. We investigated frustule and spore morphology as well as three nuclear- and three plastid-encoded markers of 85 Leptocylindrus strains from the Gulf of Naples, and one from the Atlantic US. The strains grouped into five molecularly distinct species with different levels of morphological differentiation. Two species matched the description of L. danicus and produced similar spores but differed in morphometric characters and sub-central pore position, supporting the description of L. hargravesii Nanjappa and Zingone as a distinct species. Leptocylindrus danicus var. apora French III and Hargraves, lacking a sub-central pore and not forming spores, was raised to the species level as L. aporus (French III and Hargraves) Nanjappa and Zingone. A fourth species with convex valves was described as L. convexus Nanjappa and Zingone. The fifth species matched the description of L. belgicus Meunier, considered as synonym of L. minimus. However, ultrastructural differences from all other Leptocylindrus supported the erection of the genus Tenuicylindrus Nanjappa and Zingone with T. belgicus (Meunier) Nanjappa and Zingone as type species. None of the sequences matched the L. minimus sequence in GenBank. The species analyzed showed different or partially overlapping seasonal distributions. Despite the addition of the new taxa, the ancient diatom lineage of the Leptocylindraceae shows a relative species poorness and considerable morphological stasis. PMID- 27007317 TI - Characterization of the extracellular matrix of Phaeodactylum tricornutum (Bacillariophyceae): structure, composition, and adhesive characteristics. AB - The extracellular matrix of the ovoid and fusiform morphotypes of Phaeodactylum tricornutum (Bohlin) was characterized in detail. The structural and nanophysical properties were analyzed by microscopy. Of the two morphotypes, only the ovoid form secretes adhesive mucilage; light microscopy and scanning electron microscopy images showed that the mucilage was secreted from the girdle band region of the cell as cell-substratum tethers, accumulating on the surface forming a biofilm. After 7 d, the secreted mucilage became entangled, forming adhesive strands that crisscrossed the substratum surface. In the initial secreted mucilage atomic force microscopy identified a high proportion of adhesive molecules without regular retraction curves and some modular-like adhesive molecules, in the 7 d old biofilm, the adhesive molecules were longer with fewer adhesive events but greater adhesive strength. Chemical characterization was carried out on extracted proteins and polysaccharides. Differences in protein composition, monosaccharide composition, and linkage analysis are discussed in relation to the composition of the frustule and secreted adhesive mucilage. Polysaccharide analysis showed a broad range of monosaccharides and linkages across all fractions with idiosyncratic enrichment of particular monosaccharides and linkages in each fraction. 3-linked Mannan was highly enriched in the cell frustule fractions indicating a major structural role, while Rhamnose and Fucose derivatives were enriched in the secreted fractions of the ovoid morphotype suggesting involvement in cell adhesion. Comparison of SDS-PAGE of extracellular proteins showed two major bands for the ovoid morphotype and four for the fusiform morphotype of which only one appeared to be common to both morphotypes. PMID- 27007318 TI - A new potentially toxic Azadinium species (Dinophyceae) from the Mediterranean Sea, A. dexteroporum sp. nov. AB - A new photosynthetic planktonic marine dinoflagellate, Azadinium dexteroporum sp. nov., is described from the Gulf of Naples (South Tyrrhenian Sea, Mediterranean Sea). The plate formula of the species, Po, cp, X, 4', 3a, 6", 6C, 5?S, 6''' and 2"", is typical for this recently described genus. Azadinium dexteroporum is the smallest rep-resentative of the genus (8.5 MUm average length, 6.2 MUm average width) and shares the presence of a small antapical spine with the type species A. spinosum and with A. polongum. However, it differs from all other Azadinium species for the markedly asymmetrical Po plate and the position of the ventral pore, which is located at the right posterior end of the Po plate. Another peculiarity of A. dexteroporum is the pronounced concavity of the second intercalary plate (2a), which appears collapsed with respect to the other plates. Phylogenetic analyses based on the large subunit 28S rDNA (D1/D2) and the internal transcribed spacer (ITS rDNA) support the attribution of A. dexteroporum to the genus Azadinium and its separation from the other known species. LC/MS-TOF analysis shows that Azadinium dex-teroporum produces azaspiracids in low amounts. Some of them have the same molecular weight as known compounds such as azaspiracid-3 and -7 and Compound 3 from Amphidoma languida, as well as similar fragmentation patterns in some cases. This is the first finding of a species producing azapiracids in the Mediterranean Sea. PMID- 27007319 TI - An estuarine species of the alga Vaucheria (Xanthophyceae) displays an increased capacity for turgor regulation when compared to a freshwater species. AB - Turgor regulation is the process by which walled organisms alter their internal osmotic potential to adapt to osmotic changes in the environment. Apart from a few studies on freshwater oomycetes, the ability of stramenopiles to turgor regulate has not been investigated. In this study, turgor regulation and growth were compared in two species of the stramenopile alga Vaucheria, Vaucheria erythrospora isolated from an estuarine habitat, and Vaucheria repens isolated from a freshwater habitat. Species were identified using their rbcL sequences and respective morphologies. Using a single cell pressure probe to directly measure turgor in Vaucheria after hyperosmotic shock, V. erythrospora was found to recover turgor after a larger shock than V. repens. Threshold shock values for this ability were >0.5 MPa for V. erythrospora and <0.5 MPa for V. repens. Recovery was more rapid in V. erythrospora than V. repens after comparable shocks. Turgor recovery in V. erythrospora was inhibited by Gd(3+) and TEA, suggesting a role for mechanosensitive channels, nonselective cation channels, and K(+) channels in the process. Growth studies showed that V. erythrospora was able to grow over a wider range of NaCl concentrations. These responses may underlie the ability of V. erythrospora to survive in an estuarine habitat and restrict V. repens to freshwater. The fact that both species can turgor regulate may indicate a fundamental difference between members of the Stramenopila, as research to date on oomycetes suggests they are unable to turgor regulate. PMID- 27007320 TI - Molecular and morphological diversity of Narragansett Bay (RI, USA) Ulva (Ulvales, Chlorophyta) populations. AB - Macroalgal bloom-forming species occur in coastal systems worldwide. However, due to overlapping morphologies in some taxa, accurate taxonomic assessment and classification of these species can be quite challenging. We investigated the molecular and morphological characteristics of 153 specimens of bloom-forming Ulva located in and around Narragansett Bay, RI, USA. We analyzed sequences of the nuclear internal transcribed spacer 1 region (ITS1) and the chloroplast encoded rbcL; based on the ITS1 data, we grouped the specimens into nine operational taxonomic units (OTUs). Eight of these OTUs have been previously reported to exist, while one is novel. Of the eight OTUs, all shared sequence identity with previously published sequences or differed by less than 1.5% sequence divergence for two molecular markers. Previously, 10 species names were reported for Ulva in Rhode Island (one blade and nine tube-forming species) based upon morphological classification alone. Of our nine OTUs, three contained blade forming specimens (U. lactuca, U. compressa, U. rigida), one OTU had a blade with a tubular stipe, and six contained unbranched and/or branched tubular morphologies (one of these six, U. compressa, had both a blade and a tube morphology). While the three blade-forming OTUs in Narragansett Bay can frequently be distinguished by careful observations of morphological characteristics, and spatial/temporal distribution, it is much more difficult to distinguish among the tube-forming specimens based upon morphology or distribution alone. Our data support the molecular species concept for Ulva, and indicate that molecular-based classifications of Ulva species are critical for proper species identification, and subsequent ecological assessment or mitigation of Ulva blooms. PMID- 27007321 TI - Protist distribution in the Western Fram Strait in summer 2010 based on 454 pyrosequencing of 18S rDNA. AB - In this study, we present the first comprehensive analyses of the diversity and distribution of marine protist (micro-, nano-, and picoeukaryotes) in the Western Fram Strait, using 454-pyrosequencing and high-pressure liquid chromatography (HPLC) at five stations in summer 2010. Three stations (T1; T5; T7) were influenced by Polar Water, characterized by cold water with lower salinity (<33) and different extents of ice concentrations. Atlantic Water influenced the other two stations (T6; T9). While T6 was located in the mixed water zone characterized by cold water with intermediate salinity (~33) and high ice concentrations, T9 was located in warm water with high salinity (~35) and no ice-coverage at all. General trends in community structure according to prevailing environmental settings, observed with both methods, coincided well. At two stations, T1 and T7, characterized by lower ice concentrations, diatoms (Fragilariopsis sp., Porosira sp., Thalassiosira spp.) dominated the protist community. The third station (T5) was ice-covered, but has been ice-free for ~4 weeks prior to sampling. At this station, dinoflagellates (Dinophyceae 1, Woloszynskia sp. and Gyrodinium sp.) were dominant, reflecting a post-bloom situation. At station T6 and T9, the protist communities consisted mainly of picoeukaryotes, e.g., Micromonas spp. Based on our results, 454-pyrosequencing has proven to be an adequate tool to provide comprehensive information on the composition of protist communities. Furthermore, this study suggests that a snap-shot of a few, but well-chosen samples can provide an overview of community structure patterns and succession in a dynamic marine environment. PMID- 27007322 TI - Characterization of a novel catalase-peroxidase (KATG) gene from the dinoflagellate Prorocentrum minimum. AB - Dinoflagellates are a group of eukaryotic microalgae that have many unusual cytological and genomic characteristics. Here, we report the detection of a novel catalase-peroxidase (KatG) gene from the dinoflagellate Prorocentrum minimum, and its transcript levels under copper sulfate (CuSO4 ) treatment. cDNA analysis yielded a 1,293 bp complete open reading frame (ORF) encoding a 431-amino acid (aa) polypeptide (46.6 kDa). The conserved dinoflagellate splice leader (DinoSL) indicates that this gene is nucleus encoded, and a signal sequence at the N terminus of the deduced protein indicates that the KatG protein may pass across the endoplasmic reticulum or cytoplasmic membrane, but its precise subcellular location is not known. Unlike the typical KatG proteins, P. minimum KatG (PmKatG) only has one conserved domain (N-domain). Gene expression of PmKatG dramatically increased with increasing concentrations of CuSO4 , suggesting that it functions in the defense mechanisms associated with oxidative stress. PMID- 27007324 TI - Temporal dynamics of inducible anti-herbivory defenses in the brown seaweed Ascophyllum nodosum (Phaeophyceae) (49:468-474). PMID- 27007323 TI - An online calculator for marine phytoplankton iron culturing experiments. AB - Laboratory experiments with iron offer important insight into the physiology of marine phytoplankton and the biogeochemical cycles they influence. These experiments often rely on chelators to buffer the concentration of available iron, but the buffer can fail when cell density increases, causing the concentration of that iron to drop rapidly. To more easily determine the point when the iron concentration falls, we developed an online calculator to estimate the maximum phytoplankton density that a growth medium can support. The results of the calculator were compared to the numerical simulations of a Fe-limited culture of the diatom Thalassiosira weissflogii (Grunow) Fryxell and Hasle. Modeling reveals that the assumptions behind thermodynamic estimates of unchelated Fe concentration can fail before easily perceptible changes in growth rate, potentially causing physiological changes that could alter the conclusions of culture experiments. The calculator is available at http://www.marsci.uga.edu/fidoplankter. PMID- 27007325 TI - Changes in the Immune System of Female Wistar Rats After Exposure to Immunosuppressive Treatment During Pregnancy. AB - This experimental study assessed the impact of medications frequently used after kidney transplantation on the immune system of pregnant female Wistar rats. The study evaluates medications, both approved and contraindicated during pregnancy in common therapeutic combinations. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and at 3 weeks of pregnancy. We found drug regimen-dependent differences in cytometry from spleen. Many subpopulations of lymphocytes were suppressed in rats treated with cyclosporine A, mycophenolate mofetil and prednisone and tacrolimus, mycophenolate mofetil and prednisone; the number of NK cells was increased in group of rats treated with cyclosporine A, everolimus and prednisone. We also found changes in histological examination of thymus and spleen of all treated dams. In cytokine assay, we noticed increasing levels of IL 17 with increasing doses of concanavalin A in control group and in group of dams treated with cyclosporine A, mycophenolate mofetil and prednisone. This increase was blocked in rats treated with tacrolimus, mycophenolate mofetil and prednisone and cyclosporine A, everolimus and prednisone. Qualitative, quantitative and morphological changes of immune system in pharmacologically immunosuppressed females have been observed. Thymus structure, spleen composition and splenocytes IL-17 production were mostly affected in drug regimen-dependent manner. PMID- 27007326 TI - Sandfly-Borne Phlebovirus Isolations from Turkey: New Insight into the Sandfly fever Sicilian and Sandfly fever Naples Species. AB - BACKGROUND: Many studies have presented virus sequences which suggest the existence of a variety of putative new phleboviruses transmitted by sandflies in the Old World. However, in most of these studies, only partial sequences in the polymerase or the nucleoprotein genes were characterised. Therefore to further our understand of the presence and potential medical importance of sandfly-borne phleboviruses that circulate in southern Anatolia, we initiated field campaigns in 2012 and 2013 designed to identify, isolate and characterise phleboviruses in sandflies in this region. METHODOLOGY/PRINCIPAL FINDINGS: An entomological investigation encompassing 8 villages in Adana, Mediterranean Turkey was performed in August and September 2012 and 2013. A total of 11,302 sandflies were collected and grouped into 797 pools which were tested for the presence of phleboviruses using specific primers for RT-PCR analysis and also cell culture methods for virus isolation. Seven pools were PCR positive, and viruses were isolated from three pools of sandflies, resulting in the identification of two new viruses that we named Zerdali virus and Toros virus. Phylogenetic analysis based on full-length genomic sequence showed that Zerdali virus was most closely related with Tehran virus (and belongs to the Sandfly fever Naples species), whereas Toros virus was closest to Corfou virus. CONCLUSIONS/SIGNIFICANCE: The results indicate that a variety of phleboviruses are co-circulating in this region of southern Anatolia. Based on our studies, these new viruses clearly belong to genetic groups that include several human pathogens. However, whether or not Toros and Zerdali viruses can infect humans and cause diseases such as sandfly fever remains to be investigated. PMID- 27007327 TI - Graphdiyne:ZnO Nanocomposites for High-Performance UV Photodetectors. AB - Graphdiyne (GD), a novel carbon allotrope with a 2D structure comprising benzene rings and carbon-carbon triple bonds, is successfully integrated with ZnO nanoparticles by a wet chemistry method. An ultraviolet photodetector based on these graphdiyne:ZnO nanocomposites exhibits significantly enhanced performance in comparison with a conventional ZnO device. GD may have diverse applications in future optoelectronics. PMID- 27007328 TI - Platelet-rich plasma: a case study for the identification of disinvestment opportunities using horizon scanning. AB - Objective This paper discusses the potential for horizon scanning to identify low value, inappropriate clinical practices that deliver minimal benefit to patients and represent a considerable financial burden on the health system. Methods Platelet-rich plasma (PRP) was identified by routine horizon scanning as a potentially innovative treatment alternative for osteoarthritis of the knee. A rapid, non-systematic assessment of the evidence pertaining to the safety and effectiveness of PRP compared with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of osteoarthritis of the knee was conducted. Results The evidence base supporting the use of PRP for the treatment of osteoarthritis was poor. No comparative studies were identified that compared the use of PRP to NSAIDs, the current treatment option for osteoarthritis of the knee in Australia. Despite the lack of effectiveness evidence, the use of PRP injections was rapidly increasing in the private sector using an inappropriate Medicare Benefits Schedule item number. Conclusions This assessment highlights the potential of using established horizon scanning methodologies to identify targets for full or partial disinvestment of ineffective, inefficient or harmful clinical practices. What is known about the topic? PRP is rapidly diffusing in the private health system in Australia, however the use of a Medicare Benefits Schedule item number meant that this practice was being subsidised by the public reimbursement of treatment fees. What does this paper add? Traditional horizon scanning tends to identify technologies for health systems to invest in. The evidence on the effectiveness of PRP was examined with the purpose of exploring investment in an innovative treatment that may have reduced the number of invasive procedures being performed in the public hospital system. The current evidence base does not support the use of PRP injections for the treatment of osteoarthritis. It does, however, support the use of horizon scanning as an inexpensive methodology to identify possible disinvestment targets associated with potential patient harm and high health service expenditure. What are the implications for practitioners? Practitioners should be aware that public funding for the injection of PRP should not be used for the treatment of osteoarthritis. PMID- 27007329 TI - A New View of Language Development: The Acquisition of Lexical Tone. AB - Research in first language development draws disproportionately from nontone languages. Such research is often presumed to reveal developmental universals in spite of the fact that most languages are tone languages. Recent research in the acquisition of tone languages points to a distinct course of development as compared to nontone languages. Our purpose is to provide an integrated review of research on lexical tone acquisition. First, the linguistic properties and origins of tone languages are described. Following this, research on the acquisition of tones in perception and production is reviewed and integrated. Possible reasons for the uniqueness of tone in language acquisition are discussed. Finally, theoretical advances promised by further research on tone acquisition and specific research directions are proposed. PMID- 27007330 TI - Relationship between timing of sugammadex administration and development of laryngospasm during recovery from anaesthesia when using supraglottic devices: A randomised clinical study. PMID- 27007331 TI - Antibacterial activity of silver camphorimine coordination polymers. AB - Five new silver camphorimine complexes of general formula [Ag(NO3)(Y)L] were synthesized and fully characterized using spectroscopic and analytical techniques. The structure of [Ag(NO3)(OC10H14NC6H4NC10H14O)] () was analyzed using single crystal X-ray diffraction, showing that it arranges as a coordination polymer formed by sequential Ag(NO3) units bridged by the bi-camphor ligand (). The antimicrobial properties of the new complexes were screened using the disk diffusion method and their Minimal Inhibitory Concentrations (MIC) were assessed against selected bacterial strains of the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli, Pseudomonas aeruginosa, and Burkholderia contaminans. The lowest MICs were observed for , with estimated values of 72, 20, 32 and 19 MUg mL(-1) for S. aureus, E. coli, B. contaminans, and P. aeruginosa, respectively. In the case of S. aureus, similar MIC values were obtained for silver nitrate and compound . All five compounds were bactericidal when used in concentrations equal or above the MIC value, as found by enumerating the total colony forming units (CFUs) after incubation in their presence. PMID- 27007332 TI - Exhaled breath markers of alveolar macrophage activity in sarcoidosis. AB - OBJECTIVE: Granuloma formation in sarcoidosis is dependent upon the interaction between alveolar macrophages (AMs) and a CD4+-driven TH1 response. This study aimed to measure TNF-alpha and calcium ion concentrations as markers of AM activity, in addition to total protein as a non-specific inflammatory marker in the exhaled breath condensate (EBC) of patients with sarcoidosis as well as control subjects. METHODS: EBC was collected from 17 sarcoidosis patients and 23 healthy volunteers. Protein was measured by the bicinchoninic acid assay, TNF alpha concentration was measured by ELISA and Ca(2+) concentration was measured by inductively coupled plasma-mass spectrometry. Conductivity of EBC was assessed using a conductivity probe. RESULTS: Total protein concentration was significantly elevated in EBC from patients with sarcoidosis compared to control subjects (19.51 +/- 4.52 vs. 10.60 +/- 1.31 ug/ml, p = 0.020), as was TNF-alpha (3.37 +/- 0.38 vs. 2.59 +/- 0.40 pg/ml, p = 0.037) and conductivity (66.68 +/- 16.73 vs. 36.85 +/- 3.070 uS/cm, p = 0.044). EBC Ca(2+) concentration was significantly higher in healthy controls compared to patients with sarcoidosis (116.50 +/- 12.19 vs. 73.88 +/- 13.35 umol/l, p = 0.018), although this was in the context of normal serum Ca(2+) in the sarcoidosis cohort. CONCLUSIONS: Total protein and TNF-alpha concentrations were elevated in EBC from patients with sarcoidosis and could indicate disease activity. The reduction in EBC Ca(2+) concentrations could represent granulomatous activity in the lung. PMID- 27007333 TI - Increased Plasma Levels of Heparin-Binding Protein on Admission to Intensive Care Are Associated with Respiratory and Circulatory Failure. AB - PURPOSE: Heparin-binding protein (HBP) is released by granulocytes and has been shown to increase vascular permeability in experimental investigations. Increased vascular permeability in the lungs can lead to fluid accumulation in alveoli and respiratory failure. A generalized increase in vascular permeability leads to loss of circulating blood volume and circulatory failure. We hypothesized that plasma concentrations of HBP on admission to the intensive care unit (ICU) would be associated with decreased oxygenation or circulatory failure. METHODS: This is a prospective, observational study in a mixed 8-bed ICU. We investigated concentrations of HBP in plasma at admission to the ICU from 278 patients. Simplified acute physiology score (SAPS) 3 was recorded on admission. Sequential organ failure assessment (SOFA) scores were recorded daily for three days. RESULTS: Median SAPS 3 was 58.8 (48-70) and 30-day mortality 64/278 (23%). There was an association between high plasma concentrations of HBP on admission with decreased oxygenation (p<0.001) as well as with circulatory failure (p<0.001), after 48-72 hours in the ICU. There was an association between concentrations of HBP on admission and 30-day mortality (p = 0.002). ROC curves showed areas under the curve of 0,62 for decreased oxygenation, 0,65 for circulatory failure and 0,64 for mortality. CONCLUSIONS: A high concentration of HBP in plasma on admission to the ICU is associated with respiratory and circulatory failure later during the ICU care period. It is also associated with increased 30-day mortality. Despite being an interesting biomarker for the composite ICU population it's predictive value at the individual patient level is low. PMID- 27007334 TI - Bronchoscopic Transparenchymal Nodule Access: Feasibility and Safety in an Endoscopic Unit. AB - BACKGROUND: The minimal invasive investigation of solitary pulmonary nodules becomes increasingly important with the emergence of lung cancer screening. OBJECTIVES: We report the results of the first utilization of a recently developed procedure in a bronchoscopy suite, which approaches solitary pulmonary nodules via a transparenchymal path. METHODS: This study was a prospective, single-arm interventional study. We investigated patients with a solitary pulmonary nodule detected on CT imaging, which was suspicious for malignancy. The subject's CT was employed to calculate an airway wall point of entry (POE) as well as an avascular path through lung tissue from the POE to the solitary pulmonary nodule. Using a set of catheter-based tools under fused fluoroscopy guidance, a tunnelled tract was created from the POE to the nodule. The patients were surveyed for at least 72 h in our hospital. The primary end point of the study was to evaluate the feasibility to access and biopsy solitary pulmonary nodules outside of an operation theatre. RESULTS: Six patients were recruited, and a tunnel pathway was created in 5 patients. There were no adverse events during the procedures. Two pneumothoraces were diagnosed by chest X-ray 2 h after the procedure, with one pneumothorax requiring drainage. Adequate biopsies were obtained from all 5 patients in whom a tunnel path was created. CONCLUSIONS: This study demonstrates that bronchoscopic transparenchymal access of solitary pulmonary nodules is feasible outside an operation theatre. PMID- 27007335 TI - Somatostatin Reduces the Acute Lung Injury of Mice via Increasing the Affinity of Glucocorticoid Receptor. AB - BACKGROUND/AIMS: Although it has been reported that somatostatin (SOM) upregulated the level of 90-kD heat shock protein (Hsp90), which participates in the inflammatory regulation by its client proteins, such as glucocorticoid receptor (GR), it remains unclear if it has a protective role against acute lung injury (ALI). METHODS: ALI model was established by the injection of oleic acid (OA) into the tail vein of mice. Lung injury was assessed by histological analysis, lung water content and arterial blood gases. The levels of Hsp90 and GR, the binding capacity and the affinity of GR were examined. RESULTS: It was showed that pretreatment with SOM significantly increased Hsp90 levels and alleviated lung injuries in OA-injected mice. Furthermore, SOM increased the GR expression and improved the affinity of the GR in animals with lung injury. However, little alteration was found in the maximum binding capacity of the GR in mice with or without SOM. CONCLUSION: The data indicate SOM exerts a protective effect by increasing Hsp90 abundant and further enhancing the affinity of the GR. The beneficial effects of SOM treatment provide a new strategy for modulation of GR efficiency and alleviation of acute lung injury. PMID- 27007336 TI - A Criterion for the Complete Deposition of Magnetic Beads on the Walls of Microchannels. AB - This paper analyzes numerical simulations of the trajectories of magnetic beads in a microchannel, with a nearby permanent cubical magnet, under different flow and magnetic conditions. Analytically derived local fluid velocities and local magnetic forces have been used to track the particles. A centered position and a lateral position of the magnet above the microchannel are considered. The computed fractions of deposited particles on the walls are compared successfully with a new theoretically derived criterion that imposes a relation between the sizes of the magnet and the microchannel and the particle Stokes and Alfven numbers to obtain the complete deposition of the flowing particles on the wall. In the cases in which all the particles, initially distributed uniformly across the section of the microchannel, are deposited on the walls, the simulations predict the accumulation of the major part of particles on the wall closest to the magnet and near the first half of the streamwise length of the magnet. PMID- 27007337 TI - New Technologies to Improve Root Canal Disinfection. AB - Effective irrigant delivery and agitation are prerequisites to promote root canal disinfection and debris removal and improve successful endodontic treatment. This paper presents an overview of the currently available technologies to improve the cleaning of the endodontic space and their debridement efficacy. A PubMed electronic search was conducted with appropriate key words to identify the relevant literature on this topic. After retrieving the full-text articles, all the articles were reviewed and the most appropriate were included in this review. Several different systems of mechanical activation of irrigants to improve endodontic disinfection were analysed: manual agitation with gutta-percha cones, endodontic instruments or special brushes, vibrating systems activated by low speed hand-pieces or by sonic or subsonic energy, use of ultrasonic or laser energy to mechanically activate the irrigants and apical negative pressure irrigation systems. Furthermore, this review aims to describe systems designed to improve the intracanal bacterial decontamination by a specific chemical action, such as ozone, direct laser action or light-activated disinfection. The ultrasonic activation of root canal irrigants and of sodium hypochlorite in particular still remains the gold standard to which all other systems of mechanical agitation analyzed in this article were compared. From this overview, it is evident that the use of different irrigation systems can provide several advantages in the clinical endodontic outcome and that integration of new technologies, coupled with enhanced techniques and materials, may help everyday clinical practice. PMID- 27007338 TI - Study of Anatomical Relationship between Posterior Teeth and Maxillary Sinus Floor in a Subpopulation of the Brazilian Central Region Using Cone-Beam Computed Tomography - Part 2. AB - This study evaluated the anatomical relationship between posterior teeth root apices and maxillary sinus floor (MSF) on 202 cone beam computed tomography (CBCT) exams. The distance between the root apices and the MSF, as well as the MSF thickness of the cortical bone closest to root apices and furcation regions were measured. The vertical and horizontal relationships of the MSF with the molar roots were classified into categories adapted from the criteria proposed by Kwak et al. (14). The shortest distances between MSF and the root apices were observed in the mesiobuccal root of the second molar (0.36+/-1.17 mm) and the palatal root of the first molar (0.45+/-1.10 mm) and the widest in buccal roots of the first premolars (5.47+/-4.43 mm). Significant differences were observed between the distance of MSF to the root apices of single-rooted first and second premolars. The cortical thickness ranged from 0.65+/-0.41 mm over the mesiobuccal root of the second molar to 1.28+/-0.42 mm over the buccal root of the first premolar. The most observed vertical and horizontal relationships were type II and 2H, respectively. The maxillary molar roots showed greater proximity to the MSF. The thickness of the MSF cortical bone closest to the apices and furcation regions was found to be similar only for premolars. PMID- 27007339 TI - Effect of Time Lapse on the Diagnostic Accuracy of Cone Beam Computed Tomography for Detection of Vertical Root Fractures. AB - Accurate and early diagnosis of vertical root fractures (VRFs) is imperative to prevent extensive bone loss and unnecessary endodontic and prosthodontic treatments. The aim of this study was to assess the effect of time lapse on the diagnostic accuracy of cone beam computed tomography (CBCT) for VRFs in endodontically treated dog's teeth. Forty-eight incisors and premolars of three adult male dogs underwent root canal therapy. The teeth were assigned to two groups: VRFs were artificially induced in the first group (n=24) while the teeth in the second group remained intact (n=24). The CBCT scans were obtained by NewTom 3G unit immediately after inducing VRFs and after one, two, three, four, eight, 12 and 16 weeks. Three oral and maxillofacial radiologists blinded to the date of radiographs assessed the presence/absence of VRFs on CBCT scans. The sensitivity, specificity and accuracy values were calculated and data were analyzed using SPSS v.16 software and ANOVA. The total accuracy of detection of VRFs immediately after surgery, one, two, three, four, eight, 12 and 16 weeks was 67.3%, 68.7%, 66.6%, 64.6%, 64.5%, 69.4%, 68.7%, 68% respectively. The effect of time lapse on detection of VRFs was not significant (p>0.05). Overall sensitivity, specificity and accuracy of CBCT for detection of VRFs were 74.3%, 62.2%, 67.2% respectively. Cone beam computed tomography is a valuable tool for detection of VRFs. Time lapse (four months) had no effect on detection of VRFs on CBCT scans. PMID- 27007340 TI - Safe Mechanical Preparation with Reciprocation Movement without Glide Path Creation: Result from a Pool of 673 Root Canals. AB - The aim of the present study was to prospectively assess the frequency of teeth in which the Reciproc instruments were able to reach the full working length (WL). This case series study enrolled 277 consecutive teeth requiring primary endodontic treatment performed with the Reciproc system (VDW) without a previous glide path by 3 experienced endodontists. Instruments R25, R40 or R50 were selected, respectively, for narrow, medium and large canals, according to the preoperative radiographs, as per manufacturer recommendation. Canals were instrumented and classified as reaching the full WL (RFWL) and not reaching the full WL (NRFWL), according to the ability of the Reciproc instrument to reach without a glide path the full electronically determined WL. Finally, canals were filled using a single matched cone technique. Pearson's squared-chi test compared the frequency distributions of canals classified as RFWL and NRFWL. From a total pool of 673 root canals, Reciproc instruments reached the FWL in 96.28% of cases and 3 fractures occurred. For narrow canals the percentage of RFWL was 95.37% with 3 fractures. For medium and large canals, the R40 or R50 instruments reached the FWL in 98.51% and 97.62% of the cases respectively, with no fracture. Enlarging of root canals using the Reciproc instruments up to the FWL without a glide path is successful in a great percentage of cases. This case series suggests the possibility of using a single instrument to enlarge the root canal space of teeth by a simpler approach without an a prioriglide path procedure. PMID- 27007341 TI - Influence of Apical Preparation Size and Working Length on Debris Extrusion. AB - The aim of this study was to quantitatively evaluate the amount of apically extruded debris by single-file reciprocating instruments with different working lengths and apical preparation sizes. Eighty human single-rooted mandibular incisors were used and conventional access cavities were prepared. Then, the specimens were divided into four groups (n=20), according to root canal instrumentation: Reciproc size 25, .08 taper and Reciproc size 40, .06 taper instruments were used at the foramen; Reciproc size 25, .08 taper and Reciproc size 40, .06 taper instruments were used 1 mm short of the foramen. Distilled water was used as an irrigant and the apically extruded debris were collected in pre-weighted glass vials and dried afterwards. The mean weight of debris was weighed with a microbalance and statistically analyzed using one-way analysis of variance and the post hoc Tukey multiple comparison test (p<0.05). The results showed that all experimental groups were associated with debris extrusion. No significant difference was found in the amount of apically extruded debris among all experimental groups (p>0.05). The present study demonstrated that the working length and the apical preparation size did not have a significant effect on debris extrusion when performing single-file reciprocating instrumentation. PMID- 27007342 TI - Influence of Temperature on the Antibacterial Activity of Sodium Hypochlorite. AB - The aim of this study was to compare the antimicrobial activity of 5.25% NaOCl, Hypoclean and Chlor-Xtra at 20 degrees C and 45 degrees C in bovine root dentin. One-hundred-and-seventy dentin tubes prepared from bovine maxillary incisors were infected for 21 days with Enterococcus faecalis. The specimens were divided into the following groups: 1. 5.25% NaOCl 20 degrees C; 2. Hypoclean 20 degrees C; 3. Chlor-Xtra 20 degrees C; 4. 5.25% % NaOCl 45 degrees C; 5. Hypoclean 45 degrees C; 6. Chlor-Xtra 45 degrees C; 7. positive control; 8. negative control. Dentin chips were collected with round burs into Brain Heart Infusion (BHI) broth. After culturing, the number of colony-forming units (CFU) was counted. Statistical analyses were performed using descriptive statistics (mean, standard deviation, median), Shapiro-Wilk test, ANOVA and Tukey test. Significance level was set at p<0.05. In all experimental groups, CFU was minimum after treatment (day 0) and the obtained results were significantly different from each other at any period (p<0.05). After treatment, the Hypoclean and Chlor Xtra showed the lowest numbers of CFU at 20 degrees C and 45 degrees C, whereas 5.25% NaOCl showed the highest number of CFU at both temperatures. In each group, the number of CFUs increased significantly with time (p<0.05). The antibacterial activity of Hypoclean and Chlor-Xtra at 45 degrees C were significantly greater than other tested solutions. PMID- 27007343 TI - Survival of Restored Endodontically Treated Teeth in Relation to Periodontal Status. AB - The aim of the present study was to investigate the success and survival of restored endodontically treated teeth (ETT) in a general practice environment related to periodontal parameters. Data from 360 restored ETT treated between 2000 and 2011 were collected. Dates of interventions like restorations, repairs, replacements and extractions were recorded. Additionally, general information about patients and dentitions as well as periodontal status was recorded. Success was analyzed using Kaplan-Meier statistics and a multivariate Cox regression analysis was performed to assess variables influencing success and survival. After a mean observation time of 4.34 years (range 0.6 - 11.6 years), 19 teeth were extracted and 27 restorations needed repair or replacement. According to the Cox regression, increasing maximum pocket depth of the tooth resulted in a higher risk for failure (p=0.012). In conclusion, periodontal pocket depth was found to be a significant factor in the survival of restored ETT. PMID- 27007344 TI - Effect of Argon Plasma on Root Dentin after Use of 6% NaOCl. AB - The aim of this study was to evaluate the effect of argon plasma on dentin surface after use of 6% NaOCl. Sixty bovine incisors had their crowns removed, the roots split, and the segments planed. One hundred twenty segments of the cervical third were used. The samples were divided in two groups (n=60): CONTROL GROUP: immersed in 6% NaOCl, washed, dried and then immersed in 17% EDTA, washed and dried and Argon group: after treatment described for the CONTROL GROUP, non thermal argon plasma was applied for 30 s. Ten samples were evaluated by scanning electron microscopy in each group. Other ten samples were analyzed by Fourier transform infrared spectroscopy (FTIR). Thirty samples were analyzed with a goniometer to measure the contact angle between the dentin surfaces and solutions, to determine the surface free energy. The last ten samples were used to evaluate the wettability of AH Plus sealer. Data were statistically analyzed using Kruskal Wallis and Mann-Whitney tests (p<0.05). The results of this study showed that argon plasma did not modify the surface topography. FTIR analysis showed chemical modifications after plasma treatment. Argon plasma increased the surface free energy of dentin and AH Plus wettability. In conclusion, argon plasma treatment modified chemically the dentin surface. This treatment increased the surface free energy and wettability of an epoxy resin root canal sealer, favoring its bonding to dentin surfaces. PMID- 27007346 TI - Influence of Different Intellectual Disability Levels on Caries and Periodontal Disease. AB - Oral health care is fundamental to preserve the individual integrity and consequently influences the general health. This observational, cross-sectional and analytical study evaluated the oral condition of 129 intellectually disabled individuals from the Association of Parents and Friends of Exceptional Children (APAE) in three southern Brazilian cities. Dental caries (DMFT and dmft indices) and periodontal disease (PSR index) were evaluated considering the intellectual disability level. A questionnaire on socioeconomic status (income and education level) and the last visit to a dentist was answered by the subjects' parents/guardians. The data were statistically evaluated using analysis of variance (ANOVA) and Tukey test (alpha=0.05). The mean DMFT values were 2.27, 3.76 and 0.58 (p<0.05), and the mean dmft values were 1.48, 1.55 and 2.75, respectively for subjects with mild, moderate and severe disabilities. Regarding the PSR index, 43% of the subjects presented gingivitis without retention factor (no calculus or defective margins) with no significant differences among the three disability levels. Considering the population and the limitations of this study, the subjects presenting severe disabilities showed significantly lower mean DMFT values compared to other disability levels, probably because the caretakers are responsible for the oral hygiene of such subjects. PMID- 27007345 TI - Correlation between the Mechanical Properties and Structural Characteristics of Different Fiber Posts Systems. AB - The aim of this study was to evaluate the flexural strength and flexural modulus of different fiber-reinforcement composite (FRC) posts and determine the correlation between mechanical properties and structural characteristics. Eleven brands of fiber posts were analyzed (n=10): Exacto Conico (Angelus), DT Light SL (VDW), RelyX Fiber Post (3M-Espe), Glassix Radiopaque (Nordim), Para Post Fiber White (Coltene), FRC Postec Plus (Ivoclar), Aestheti-Plus Post (Bisco), Superpost Conico Estriado (Superdont), Superpost Ultrafine (Superdont), Reforpost (Angelus), and White Post DC (FGM). The posts were loaded in three-point bending test to calculate the flexural strength and flexural modulus using a mechanical testing machine (EMIC 2000 DL) at 0.5 mm/min. Data were submitted to one-way ANOVA and Scott-Knot test (p<0.05). The cross-sections of the posts were examined by scanning electron microscopy (SEM). Correlation between the mechanical properties and each of the structural variables was calculated by Pearson's correlation coefficients (p<0.05). The flexural strength values ranged from 493 to 835 MPa and were directly correlated with the fiber/matrix ratio (p=0.011). The flexural modulus ranged from 4500 to 8824 MPa and was inversely correlated with the number of fibers per mm2 of post (p<0.001). It was concluded that the structural characteristics significantly affected the properties of the FRC posts. The structural characteristic and mechanical properties of fiber glass posts are manufacture-dependent. A linear correlation between flexural strength and fiber/matrix ratio, as well as the flexural modulus and the amount of fiber was found. PMID- 27007347 TI - In Situ and In Vitro Effects of Two Bleaching Treatments on Human Enamel Hardness. AB - The aim of this study was to evaluate in vitro and in situ the effects of two bleaching treatments on human enamel surface microhardness. Sixty enamel slabs from recently extracted thirty molars were used. The specimens were polished with sandpapers under water-cooling. The enamel samples were randomly divided in four groups, treated with 10% hydrogen peroxide (HP) or Whitening Strips (WS) containing 10% hydrogen peroxide and using two conditions: in vitro or in situ model. For in situ condition, six volunteers wore an intra-oral appliance containing enamel slabs, while for in vitro condition the specimens were kept in deionized water after the bleaching protocols. The bleaching treatments were applied one-hour daily for 14 days. Similar amounts of bleaching agents were used in both conditions. Before and after bleaching treatments, microhardness was measured. Statistical analysis (ANOVA and Tukey test) showed that in the in situ condition there was no statistically significant microhardness reduction in the bleached enamel (p>0.05). Significant decrease in hardness was observed for enamel slabs bleached with both treatments in the in vitro condition (p<0.05). Regarding the bleaching agents, in situ results showed no difference between HP and WS, while in vitro WS produced the lowest hardness value. It could be concluded that there was no deleterious effect on enamel produced by any of the bleaching protocols used in the in situ model. The reduction of hardness was only observed in vitro. PMID- 27007348 TI - Personality Style in Patients Looking for Tooth Bleaching and Its Correlation with Treatment Satisfaction. AB - In the last years the focus in dentistry has shifted to an "esthetic dentistry" approach, where patients are concerned about reaching a better look of their teeth. Vital tooth bleaching is a technique with immediate results, which improves the appearance and patient's self-esteem. The aim of this study was to recognize personality characteristics determined by the Millon Index of Personality Styles of participants looking for tooth bleaching and to correlate them to satisfaction with the treatment. Forty participants were included and filled out the Millon Index of Personality Styles form before treatment. Expectation about tooth bleaching was quantified from 1 to 5. Patients were treated with bleaching agent according to manufacturer's directions. One week after treatment, the patient's satisfaction was quantified from 1 to 5. Prevailing personality characteristics were determined. Expectations and satisfaction values of all patients were correlated with each of the presented personality scales by Spearman Rho test. Ten scales prevailed over their counterpart. Median of patient's expectation was 2 and satisfaction 4. Only the score of a single characteristic (extraversing) showed statistically significant correlation with patient satisfaction. Patients looking for tooth bleaching treatment seem to have common personality characteristics. Almost all of them wanted to achieve a moderate change in teeth color and the result of the treatment was usually satisfactory. PMID- 27007349 TI - Peptide Characterization of Mature Fluorotic and Control Human Enamel. AB - Exposure to high fluoride levels during amelogenesis causes enamel fluorosis. This study aimed to determine and compare the amino acid sequences in the enamel of fluorotic and control teeth. This investigation included enamel samples obtained from erupted and non-erupted third molars with either TF grade 4-6 (n=7) fluorosis or no sign of fluorosis (controls, n=7). The samples were kept frozen at -20 degrees C until protein extraction. Samples were etched and processed with a cocktail of proteinase inhibitors and immediately analyzed. Matrix Assisted Laser Desorption/Ionization-Time-Of-Flight/Time-of-Flight Mass Spectrometry (MALDI-TOF/TOF) followed by MASCOT search aided the peptides analysis. The more abundant peptides bore the N-terminal amelogenin sequences WYQSIRPPYP (which is specific for the X-encoded amelogenin) and MPLPPHPGHPGYINF (which does not show sexual dimorphism) were not different in control or fluorotic enamel. There was no missing proteolytic cleavage in the fluorotic samples, which suggested that the increased amount of protein described in fluorotic enamel did not stem from the decreased ability of proteinases to cleave the proteins in humans. This study showed how to successfully obtain peptide from superficial enamel. A relatively low number of teeth was sufficient to provide good data on the actual peptides found in mature enamel. PMID- 27007350 TI - Association between Dental Caries and Socioeconomic Factors in Schoolchildren--A Multilevel Analysis. AB - This study aimed to assess the association between dental caries, socioeconomic individual and contextual factors in 12-years-old children. A representative sample of 1,134 children enrolled in public schools from Santa Maria, RS, Brazil, was obtained from a multistage random sampling. Four calibrated dentists examined participants at schools. Data about dental caries (DMF-T index) and dental plaque (present or absent) were assessed. Children's parents or guardians answered questions regarding their demographics and socioeconomic status. Context variables were also collected from official publications of the city. Data analyses were performed using multilevel logistic regression models. Caries prevalence in this sample (DMF-T>=1) was 49.9% (95%CI: 45.05% - 54.77%), and mean DMF-T was 1.15 (95%CI: 1.01-1.29) with 0.068 standard error. Children of the 3rd and 2nd tertile of income represented by the rich and intermediate categories, showed, respectively, a 50% (OR 0.50: CI95 % 0.35-0.71) and 39% (OR 0.61: CI95% 0.45-0.82) lower chance to present untreated caries compared with the poorest portion of the sample represented by the 1st tertile of income. Regarding the context covariates, children from lower income neighborhood presented a higher chance for having untreated dental caries compared with their counterpart (OR 1.70: CI95% 1.19 to 2.43). Inequalities in the distribution of dental caries continue affecting children from poorer socioeconomic profiles. There is need for planning public interventions for oral health promotion that take into account individual and contextual socioeconomic characteristics. PMID- 27007351 TI - Clinical Efficacy of Fluoride Varnish and Low-Level Laser Radiation in Treating Dentin Hypersensitivity. AB - The objective of this study was to compare the efficacy of fluoride varnish (Fluorniz(r)) and irradiation with a gallium-arsenide-aluminum diode laser in the treatment of cervical dentin hypersensitivity. Cervical dentin hypersensitivity (CDH) is a painful condition that is highly prevalent in the world's adult population, with one in six patients presenting this symptom. Eighty-six teeth were divided into two groups: Group 1, teeth treated with Fluorniz; Group 2, teeth irradiated with a GaAlAs laser at a 4 J/cm2 dose. The two treatments were applied to the buccal cervical region in four sessions, at intervals of 72 to 96 h. The response of the patient to tactile and thermal-evaporative stimuli was rated on a visual analog scale. The results showed a reduction of hypersensitivity in response to tactile and thermal-evaporative stimulation at the end of treatment in both groups. In conclusion, short-term treatment with Fluorniz was found to be more effective than low-level laser radiation in reducing cervical dentin hypersensitivity. PMID- 27007352 TI - Influence of Photoinitiator and Light-Curing Source on Bond Strength of Experimental Resin Cements to Dentin. AB - This study evaluated the bond strength (BS) of experimental resin cements formulated with different photoinitiators when activated by two kinds of light curing units (LCUs) through a ceramic material. Seven resin blends with different camphorquinone (CQ) and/or phenylpropanedione (PPD) concentrations (weight) were prepared: C5: 0.5% CQ; C8: 0.8% CQ; P5: 0.5% PPD; P8: 0.8% PPD; C1P4: 0.1% CQ and 0.4% PPD; C4P1: 0.4% CQ and 0.1% PPD; C4P4: 0.4% CQ and 0.4% PPD. Two LCUs were used: one quartz-tungsten-halogen (QTH - 850 mW/cm2) and one light-emitting diode (LED - 1300 mW/cm2). The microtensile bond strength of each blend was assessed. Data were submitted to two-way ANOVA and Tukey's test (alpha=0.05). The BS values did not exhibit significant differences for LCUs, regardless of the photoinitiator type. Three cements showed significant differences: P5 and C5 had higher BS with QTH, and C4P1 with LED. For QTH, P5 showed the highest and C1P4 the lowest BS. For the LED, C4P1 showed the highest BS of all the cements. The results indicated that PPD was a viable alternative in the formulation of photocured resin cements, reducing or eliminating CQ that is yellowish without impairing the bond strength. Furthermore, both LED and QTH were effective in curing resin cements that contain PPD or CQ. PMID- 27007353 TI - Active and Passive Application of the Phosphoric Acid on the Bond Strength of Lithium Disilicate. AB - The objective of this study was to evaluate the effect of passive or active phosphoric acid (PA) application after hydrofluoric acid (HA) treatment on the microshear bond strength of lithium disilicate. Thirty ceramic discs were made with IPS Emax 2 (10 mm thick and 10 mm diameter). The specimens were divided into 3 groups, A: 9.6% HA application; AF: 9.6% HA application + cleaning with 37% PA in passive mode and AFF: 9.6% HA application + cleaning with 37% PA in active mode. For the microshear test, four tygons (0.9 mm diameter and 0.2 mm high) were filled with resin cement (RelyX Ultimate) and placed on the ceramic disks. After testing, the fracture modes were examined under scanning electron microscopy. Data were analyzed by one-way ANOVA and Tukey's post test (alpha=0.05). The bond strength values were significantly higher in Group AFF (11.0+/-2.5 MPa) compared with group A (8.1+/-2.6 MPa) (p<0.002). AF group was not statistically different (9.4+/-2.5 MPa) from Group A. It was concluded that the active application of 37% PA after 9.6% HA increases the microshear bond strength values between the resin cement and lithium disilicate ceramic. PMID- 27007354 TI - Influence of Different Types of Resin Luting Agents on Color Stability of Ceramic Laminate Veneers Subjected to Accelerated Artificial Aging. AB - The aim of this study was to evaluate the influence of accelerated aging (AAA) on the color stability of resin cements for bonding ceramic laminate veneers of different thicknesses. The occlusal surfaces of 80 healthy human molars were flattened. Ceramic laminate veneers (IPS e-max Ceram) of two thicknesses (0.5 and 1.0 mm) were bonded with three types of luting agents: light-cured, conventional dual and self-adhesive dual cement. Teeth without restorations and cement samples (0.5 mm) were used as control. After initial color evaluations, the samples were subjected to AAA for 580 h. After this, new color readouts were made, and the color stability (DeltaE) and luminosity (DeltaL) data were analyzed. The greatest color changes (p<0.05) occurred when 0.5 mm veneers were fixed with light-cured cement and the lowest when 1.0 mm veneers were fixed with conventional dual cement. There was no influence of the restoration thickness when the self adhesive dual cement was used. When veneers were compared with the control groups, it was verified that the cement samples presented the greatest alterations (p<0.05) in comparison with both substrates and restored teeth. Therefore, it was concluded that the thickness of the restoration influences color and luminosity changes for conventional dual and light-cured cements. The changes in self-adhesive cement do not depend on restoration thickness. PMID- 27007355 TI - Fluoride-Releasing Materials to Prevent White Spot Lesions around Orthodontic Brackets: A Systematic Review. AB - The relation between orthodontic fixed appliances use and enamel demineralization is well established. Different preventive approaches have been suggested to this problem, but controversy remains about which is the best. The aim of this study was to perform a systematic review of clinical trials that investigated the effectiveness of materials containing fluorides to lute brackets or cover the bonding interface in order to inhibit the development and progression of white spot lesions. The null hypothesis was that fluoride materials do not affect the incidence of white spot lesions around brackets. A MEDLINE search was conducted for randomized clinical trials evaluating the development of white spot lesions in patients using fixed orthodontic appliances, followed by meta-analysis comparing the results for patients for whom dental materials containing fluorides were used (experimental group) to those for whom these materials were not used (control group). The pooled relative risk of developing white spot lesions for the experimental group was 0.42 (95% confidence interval: 0.25 to 0.72); hence, when fluoride-releasing materials are used, the patient has 58% less risk of white spot lesion development. Regarding white spot lesion extent, the pooled mean difference between the experimental and control groups was not statistically significant (-0.12; 95% confidence interval: -0.29 to 0.04). In conclusion, the results of the present systematic review suggest that fluoride-releasing materials can reduce the risk of white spot lesions around brackets. However, when white spot lesions had already occurred, there is no evidence that fluoride releasing materials reduce the extent of these lesions. PMID- 27007356 TI - Cytotoxic Effect of Erythroxylum suberosum Combined with Radiotherapy in Head and Neck Cancer Cell Lines. AB - The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. PMID- 27007358 TI - Clean Transformation of Ethanol to Useful Chemicals. The Behavior of a Gold Modified Silicalite Catalyst. AB - Upon addition of gold to silicalite-1 pellets (a MFI-type zeolite), the vapor phase oxidation of ethanol could be addressed to acetaldehyde or acetic acid formation. By optimizing the catalyst composition and reaction conditions, the conversion of ethanol could be tuned to acetaldehyde with 97% selectivity at 71% conversion or to acetic acid with 78% selectivity at total conversion. Considering that unloaded silicalite-1 was found to catalyze the dehydration of ethanol to diethylether or ethene, a green approach for the integrated production of four important chemicals is herein presented. This is based on renewable ethanol as a reagent and a modular catalytic process. PMID- 27007357 TI - Casticin Inhibits A375.S2 Human Melanoma Cell Migration/Invasion through Downregulating NF-kappaB and Matrix Metalloproteinase-2 and -1. AB - Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti metastasis effects of casticin on A375.S2 melanoma cells by using a non-lethal concentration. First; we used an adhesion assay to test the A375.S2 cells' adhesion ability after treatment with casticin. We next investigated the cell migration ability after casticin treatment by using a wound healing assay to prove that the migration of A375.S2 cells can be inhibited by casticin and double checked the results using the transwell-migration assay. The suppressive effects on matrix metalloproteinase-2; and -9 (MMP-2; and -9) activities were examined by gelatin zymography. Furthermore, western blotting was used to investigate the protein level changes in A375.S2 cells. We found that p-EGFR; Ras and p-ERK1/2 are decreased by casticin, indicating that casticin can down-regulate the migration and invasion ability of A375.S2 cells via the p-EGFR/Ras/p-ERK pathway. The NF-kappaB p65 and p-ERK levels in nuclear proteins are also decreased by treatment with casticin. An EMSA assay also discovered that the NF-kappaB p65 and DNA interaction is decreased. NF-kappaB p65 protein level was examined by immunofluorescence staining and also decreased. Our findings suggest that casticin has anti-metastatic potential by decreasing the invasiveness of A375.S2 cells. We also found that casticin suppressed A375.S2 cell proliferation and cell adhesion ability, but did not affect cell death, as examined using cytometry and a collagen adhesion assay. Based on these observations, casticin could be used as an inhibitor of migration and invasion of human melanoma cells in the future. PMID- 27007359 TI - Effects of Astaxanthin from Litopenaeus Vannamei on Carrageenan-Induced Edema and Pain Behavior in Mice. AB - Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from astaxanthin treatment in mice: an inhibition of paw edema induced in hind paw, an increase in mechanical paw withdrawal threshold and thermal paw withdrawal latency, and a reduction in the amount of myeloperoxidase enzyme and lipid peroxidation products in the paw. Furthermore the effect was comparable to indomethacin, a standard treatment for inflammation symptoms. Due to adverse effects of indomethacin on cardiovascular and gastrointestinal systems, our study suggests promising prospect of astaxanthin extract as an anti-inflammatory alternative against carrageenan-induced paw edema and pain behavior. PMID- 27007361 TI - Fluidized Bed Membrane Reactors for Ultra Pure H2 Production--A Step forward towards Commercialization. AB - In this research the performance of a fluidized bed membrane reactor for high temperature water gas shift and its long term stability was investigated to provide a proof-of-concept of the new system at lab scale. A demonstration unit with a capacity of 1 Nm3/h of ultra-pure H2 was designed, built and operated over 900 h of continuous work. Firstly, the performance of the membranes were investigated at different inlet gas compositions and at different temperatures and H2 partial pressure differences. The membranes showed very high H2 fluxes (3.89 * 10(-6) mol.m(-2).Pa(-1).s(-1) at 400 degrees C and 1 atm pressure difference) with a H2/N2 ideal perm-selectivity (up to 21,000 when integrating five membranes in the module) beyond the DOE 2015 targets. Monitoring the performance of the membranes and the reactor confirmed a very stable performance of the unit for continuous high temperature water gas shift under bubbling fluidization conditions. Several experiments were carried out at different temperatures, pressures and various inlet compositions to determine the optimum operating window for the reactor. The obtained results showed high hydrogen recovery factors, and very low CO concentrations at the permeate side (in average <10 ppm), so that the produced hydrogen can be directly fed to a low temperature PEM fuel cell. PMID- 27007360 TI - A New Megastigmane Sesquiterpenoid from Zanthoxylum Schinifolium Sieb. et Zucc. AB - Zanthoxylum schinifolium Sieb. et Zucc. (Rutaceae), a dioecious shrub with hooked prickly branches, has been used as folk medicine for the treatment of the common cold, stomach ache, diarrhea, and jaundice in China, Korea, and Japan. In our phytochemical investigations on this genus, a new megastigmane sesquiterpenoid, which is referred to as schinifolenol A (1), was isolated from Z. schinifolium. The stereochemistry was characterized via the analyses of extensive spectra. The absolute configuration was established by the application of a modified Mosher's experiment and assisted by a time-dependent density functional theory (TD-DFT) on calculated electronic circular dichroism (ECD). Bioactivity screenings showed that compound 1 exhibited a safe hypotoxicity and a better selectivity on anti Kaposi's sarcoma associated herpes virus (KSHV). PMID- 27007362 TI - Synthesis and Evaluation of Ester Derivatives of 10-Hydroxycanthin-6-one as Potential Antimicrobial Agents. AB - As part of our continuing research on canthin-6-one antimicrobial agents, a new series of ester derivatives of 10-hydroxycanthin-6-one were synthesized using a simple and effective synthetic route. The structure of each compound was characterized by NMR, ESI-MS, FT-IR, UV, and elemental analysis. The antimicrobial activity of these compounds against three phytopathogenic fungi (Alternaria solani, Fusarium graminearum, and Fusarium solani) and four bacteria (Bacillus cereus, Bacillus subtilis, Ralstonia solanacearum, and Pseudomonas syringae) were evaluated using the mycelium linear growth rate method and micro broth dilution method, respectively. The structure-activity relationship is discussed. Of the tested compounds, 4 and 7s displayed significant antifungal activity against F. graminearum, with inhibition rates of 100% at a concentration of 50 MUg/mL. Compounds 5, 7s, and 7t showed the best inhibitory activity against all the tested bacteria, with minimum inhibitory concentrations (MICs) between 3.91 and 31.25 MUg/mL. Thus, 7s emerged as a promising lead compound for the development of novel canthine-6-one antimicrobial agents. PMID- 27007363 TI - Synthesis and Biological Evaluation of an (18)Fluorine-Labeled COX Inhibitor- [(18)F]Fluorooctyl Fenbufen Amide--For Imaging of Brain Tumors. AB - Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared from 8 chlorooctanol via treatment with potassium phthalimide, tosylation with Ts2O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [(18)F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [(18)F]F(-) (212 mCi) via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown to exceed 22 GBq/MUmol (EOS) based on decay-corrected calculations. Ex-vivo analysis of [(18)F]FOFA in plasma using HPLC showed that the agent had a half-life of 15 min. PET scanning showed significant accumulation of [(18)F]FOFA over tumor loci with reasonable contrast in C6-glioma bearing rats. These results suggest that this molecule is a promising agent for the visualization of brain tumors. Further investigations should focus on tumor micro environments. PMID- 27007364 TI - A Solvent-Free Surface Suspension Melt Technique for Making Biodegradable PCL Membrane Scaffolds for Tissue Engineering Applications. AB - In tissue engineering, there is limited availability of a simple, fast and solvent-free process for fabricating micro-porous thin membrane scaffolds. This paper presents the first report of a novel surface suspension melt technique to fabricate a micro-porous thin membrane scaffolds without using any organic solvent. Briefly, a layer of polycaprolactone (PCL) particles is directly spread on top of water in the form of a suspension. After that, with the use of heat, the powder layer is transformed into a melted layer, and following cooling, a thin membrane is obtained. Two different sizes of PCL powder particles (100 um and 500 um) are used. Results show that membranes made from 100 um powders have lower thickness, smaller pore size, smoother surface, higher value of stiffness but lower ultimate tensile load compared to membranes made from 500 um powder. C2C12 cell culture results indicate that the membrane supports cell growth and differentiation. Thus, this novel membrane generation method holds great promise for tissue engineering. PMID- 27007365 TI - Antibacterial Activity and Action Mechanism of the Essential Oil from Enteromorpha linza L. against Foodborne Pathogenic Bacteria. AB - Foodborne illness and disease caused by foodborne pathogenic bacteria is continuing to increase day by day and it has become an important topic of concern among various food industries. Many types of synthetic antibacterial agents have been used in food processing and food preservation; however, they are not safe and have resulted in various health-related issues. Therefore, in the present study, essential oil from an edible seaweed, Enteromorpha linza (AEO), was evaluated for its antibacterial activity against foodborne pathogens, along with the mechanism of its antibacterial action. AEO at 25 mg/disc was highly active against Bacillus cereus (12.3-12.7 mm inhibition zone) and Staphylococcus aureus (12.7-13.3 mm inhibition zone). The minimum inhibitory concentration and minimum bactericidal concentration values of AEO ranged from 12.5-25 mg/mL. Further investigation of the mechanism of action of AEO revealed its strong impairing effect on the viability of bacterial cells and membrane permeability, as indicated by a significant increase in leakage of 260 nm absorbing materials and K+ ions from the cell membrane and loss of high salt tolerance. Taken together, these data suggest that AEO has the potential for use as an effective antibacterial agent that functions by impairing cell membrane permeability via morphological alternations, resulting in cellular lysis and cell death. PMID- 27007366 TI - Deoxyelephantopin from Elephantopus scaber Inhibits HCT116 Human Colorectal Carcinoma Cell Growth through Apoptosis and Cell Cycle Arrest. AB - Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death in HCT116 cells. The anticancer activity of DET was evaluated by a MTT assay. Morphological and biochemical changes were detected by Hoescht 33342/PI and Annexin V/PI staining. The results revealed that DET and isodeoxyelephantopin (isoDET) could be isolated from the ethyl acetate fraction of E. scaber leaves via a bioassay guided approach. DET induced significant dose- and time-dependent growth inhibition of HCT116 cells. Characteristics of apoptosis including nuclear morphological changes and externalization of phosphatidylserine were observed. DET also significantly resulted in the activation of caspase-3 and PARP cleavage. Additionally, DET induced cell cycle arrest at the S phase along with dose dependent upregulation of p21 and phosphorylated p53 protein expression. DET dose dependently downregulated cyclin D1, A2, B1, E2, CDK4 and CDK2 protein expression. In conclusion, our data showed that DET induced apoptosis and cell cycle arrest in HCT116 colorectal carcinoma, suggesting that DET has potential as an anticancer agent for colorectal carcinoma. PMID- 27007367 TI - Screening of Satureja subspicata Vis. Honey by HPLC-DAD, GC-FID/MS and UV/VIS: Prephenate Derivatives as Biomarkers. AB - The samples of Satureja subspicata Vis. honey were confirmed to be unifloral by melissopalynological analysis with the characteristic pollen share from 36% to 71%. Bioprospecting of the samples was performed by HPLC-DAD, GC-FID/MS, and UV/VIS. Prephenate derivatives were shown to be dominant by the HPLC-DAD analysis, particularly phenylalanine (167.8 mg/kg) and methyl syringate (MSYR, 114.1 mg/kg), followed by tyrosine and benzoic acid. Higher amounts of MSYR (3-4 times) can be pointed out for distinguishing S. subspicata Vis. honey from other Satureja spp. honey types. GC-FID/MS analysis of ultrasonic solvent extracts of the samples revealed MSYR (46.68%, solvent pentane/Et2O 1:2 (v/v); 52.98%, solvent CH2Cl2) and minor abundance of other volatile prephenate derivatives, as well as higher aliphatic compounds characteristic of the comb environment. Two combined extracts (according to the solvents) of all samples were evaluated for their antioxidant properties by FRAP and DPPH assay; the combined extracts demonstrated higher activity (at lower concentrations) in comparison with the average honey sample. UV/VIS analysis of the samples was applied for determination of CIE Lab colour coordinates, total phenolics (425.38 mg GAE/kg), and antioxidant properties (4.26 mmol Fe(2+)/kg (FRAP assay) and 0.8 mmol TEAC/kg (DDPH assay)). PMID- 27007368 TI - Isoquercitrin Inhibits Hydrogen Peroxide-Induced Apoptosis of EA.hy926 Cells via the PI3K/Akt/GSK3beta Signaling Pathway. AB - Oxidative stress plays a critical role in endothelial injury and the pathogenesis of diverse cardiovascular diseases, including atherosclerosis. Isoquercitrin (quercetin-3-glucoside), a flavonoid distributed widely in plants, exhibits many biological activities, including anti-allergic, anti-viral, anti-inflammatory, and anti-oxidative effects. In the present study, the inhibitory effect of isoquercitrin on H2O2-induced apoptosis of EA.hy926 cells was evaluated. MTT assays showed that isoquercitrin significantly inhibited H2O2-induced loss of viability in EA.hy926 cells. Hoechst33342/PI and Annexin V-FITC/PI fluorescent double staining indicated that isoquercitrin inhibited H2O2-induced apoptosis of EA.hy926 cells. Western blotting demonstrated that isoquercitrin prevented H2O2 induced increases in cleaved caspase-9 and cleaved caspase-3 expression, while increasing expression of anti-apoptotic protein Mcl-1. Additionally, isoquercitrin significantly increased the expression of p-Akt and p-GSK3beta in a dose-dependent manner in EA.hy926 cells. LY294002, a PI3K/Akt inhibitor, inhibited isoquercitrin-induced GSK3beta phosphorylation and increase of Mcl-1 expression, which indicated that regulation of isoquercitrin on Mcl-1 expression was likely related to the modulation of Akt activation. These results demonstrated that the anti-apoptotic effect of isoquercitrin on H2O2-induced EA.hy926 cells was likely associated with the regulation of isoquercitrin on Akt/GSK3beta signaling pathway and that isoquercitrin could be used clinically to interfere with the progression of endothelial injury-associated cardiovascular disease. PMID- 27007369 TI - Trapa japonica Pericarp Extract Reduces LPS-Induced Inflammation in Macrophages and Acute Lung Injury in Mice. AB - In this study, we found that chloroform fraction (CF) from TJP ethanolic extract inhibited lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and intracellular ROS in RAW264.7 cells. In addition, expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes was reduced, as evidenced by western blot. Our results indicate that CF exerts anti-inflammatory effects by down-regulating expression of iNOS and COX-2 genes through inhibition of MAPK (ERK, JNK and p38) and NF-kappaB signaling. Similarly we also evaluated the effects of CF on LPS-induced acute lung injury. Male Balb/c mice were pretreated with dexamethasone or CF 1 h before intranasal instillation of LPS. Eight hours after LPS administration, the inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The results indicated that CF inhibited LPS-induced TNF-alpha and IL-6 production in a dose dependent manner. It was also observed that CF attenuated LPS-induced lung histopathologic changes. In conclusion, these data demonstrate that the protective effect of CF on LPS-induced acute lung injury (ALI) in mice might relate to the suppression of excessive inflammatory responses in lung tissue. Thus, it can be suggested that CF might be a potential therapeutic agent for ALI. PMID- 27007370 TI - Synthesis, Characterization, and Antifungal Activity of Phenylpyrrole-Substituted Tetramic Acids Bearing Carbonates. AB - For the aim of discovering new fungicide, a series of phenylpyrrole-substituted tetramic acid derivatives bearing carbonates 6a-q were designed and synthesized via 4-(2,4-dioxopyrrolidin-3-ylidene)-4-(phenylamino)butanoic acids 4a-k and the cyclized products 1',3,4,5'-tetrahydro-[2,3'-bipyrrolylidene]-2',4',5(1H)-triones 5a-k. The compounds were characterized using IR, 1H- and (13)C-NMR spectroscopy, mass spectrometry (EI-MS), and elemental analysis. The structure of 6b was confirmed by X-ray diffraction crystallography. The title compounds 6a-q were bioassayed in vitro against the phytopathogenic fungi Fusarium graminearum, Botrytis cinerea and Rhizoctonia solani at a concentration of 100 MUg/mL, respectively. Most compounds displayed good inhibitory activity. PMID- 27007371 TI - A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs. AB - Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor) and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p) level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel) and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5-3.5 logP values). The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3-255 A2. Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA) values, exhibit the largest absorption. A high value of polar surface area (PSA) of cangrelor (255 A2) results in substantial worsening of the absorption in comparison with thienopyridine drugs. PMID- 27007372 TI - Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis. AB - The Aquilaria malaccensis (Thymelaeaceae) tree is a source of precious fragrant resin, called agarwood, which is widely used in traditional medicines in East Asia against diseases such as asthma. In our continuous search for active natural products, A. malaccensis seeds ethanolic extract demonstrated antiallergic effect with an IC50 value less than 1 ug/mL. Therefore, the present research aimed to purify and identify the antiallergic principle of A. malaccensis through a bioactivity-guided fractionation approach. We found that phorbol ester-rich fraction was responsible for the antiallergic activity of A. malaccensis seeds. One new active phorbol ester, 12-O-(2Z,4E,6E)-tetradeca-2,4,6-trienoylphorbol-13 acetate, aquimavitalin (1) was isolated. The structure of 1 was assigned by means of 1D and 2D NMR data and high-resolution mass spectrometry (HR-MS). Aquimavitalin (1) showed strong inhibitory activity in A23187- and antigen induced degranulation assay with IC50 values of 1.7 and 11 nM, respectively, with a therapeutic index up to 71,000. The antiallergic activities of A. malaccensis seeds and aquimavitalin (1) have never been revealed before. The results indicated that A. malaccensis seeds and the pure compound have the potential for use in the treatment of allergy. PMID- 27007373 TI - Efficient Data Gathering in 3D Linear Underwater Wireless Sensor Networks Using Sink Mobility. AB - Due to the unpleasant and unpredictable underwater environment, designing an energy-efficient routing protocol for underwater wireless sensor networks (UWSNs) demands more accuracy and extra computations. In the proposed scheme, we introduce a mobile sink (MS), i.e., an autonomous underwater vehicle (AUV), and also courier nodes (CNs), to minimize the energy consumption of nodes. MS and CNs stop at specific stops for data gathering; later on, CNs forward the received data to the MS for further transmission. By the mobility of CNs and MS, the overall energy consumption of nodes is minimized. We perform simulations to investigate the performance of the proposed scheme and compare it to preexisting techniques. Simulation results are compared in terms of network lifetime, throughput, path loss, transmission loss and packet drop ratio. The results show that the proposed technique performs better in terms of network lifetime, throughput, path loss and scalability. PMID- 27007374 TI - Development of a Tri-Axial Cutting Force Sensor for the Milling Process. AB - This paper presents a three-component fixed dynamometer based on a strain gauge, which reduces output errors produced by the cutting force imposed on different milling positions of the workpiece. A reformative structure of tri-layer cross beams is proposed, sensitive areas were selected, and corresponding measuring circuits were arranged to decrease the inaccuracy brought about by positional variation. To simulate the situation with a milling cutter moving on the workpiece and validate the function of reducing the output errors when the milling position changes, both static calibration and dynamic milling tests were implemented on different parts of the workpiece. Static experiment results indicate that with standard loads imposed, the maximal deviation between the measured forces and the standard inputs is 4.87%. The results of the dynamic milling test illustrate that with identical machining parameters, the differences in output variation between the developed sensor and standard dynamometer are no larger than 6.61%. Both static and dynamic experimental results demonstrate that the developed dynamometer is suitable for measuring milling force imposed on different positions of the workpiece, which shows potential applicability in machining a monitoring system. PMID- 27007375 TI - Designing Mobile Applications for Emergency Response: Citizens Acting as Human Sensors. AB - When an emergency occurs, citizens can be a helpful support for the operation centers involved in the response activities. As witnesses to a crisis, they initially can share updated and detailed information about what is going on. Moreover, thanks to the current technological evolution people are able to quickly and easily gather rich information and transmit it through different communication channels. Indeed, modern mobile devices embed several sensors such as GPS receivers, Wi-Fi, accelerometers or cameras that can transform users into well-equipped human sensors. For these reasons, emergency organizations and small and medium enterprises have demonstrated a growing interest in developing smart applications for reporting any exceptional circumstances. In this paper, we present a practical study about this kind of applications for identifying both limitations and common features. Based on a study of relevant existent contributions in this area and our personal direct experience in developing and evaluating emergency management solutions, our aim is to propose several findings about how to design effective and efficient mobile emergency notification applications. For this purpose we have exploited the basic sensors of modern mobile devices and the users' aptitude for using them. The evaluation consists of a practical and a theoretical part. In the practical part, we have simulated a traffic accident as closely as possible to a real scenario, with a victim lying on the ground near a car in the middle of a street. For the theoretical part, we have interviewed some emergency experts for collecting their opinions about the utility of the proposed solution. Results from this evaluation phase confirm the positive impact that EN application have for both operators' and citizens' perspective. Moreover, we collected several findings useful for future design challenges in the same area, as shown in the final redesign of the proposed application. PMID- 27007377 TI - Theoretical and Experimental Analysis of an Induction Planar Actuator with Different Secondaries--A Planar Driver Application for Metallic Surface Inspection. AB - This paper presents a study on an induction planar actuator concept. The device uses the same principles as a linear induction motor in which the interaction between a travelling magnetic field and a conducting surface produces eddy currents that leads to the generation of a thrust force and can result in movement over a metallic surface. This can benefit the inspection of metallic surfaces based on the driving platform provided by the induction planar actuator. Equations of the magnetic and electric fields are presented and, by means of these equations, the forces involved were calculated. The behaviour of thrust and normal forces was analysed through the equations and by numerical models, and compared with the results obtained by measurements on a device prototype built in the laboratory as part of the study. With relation to the surface under inspection that forms the secondary, three cases were analysed: (1) a double layered secondary formed by aluminium and ferromagnetic slabs; (2) a single aluminium layer and (3) a single ferromagnetic layer. Theoretical and measured values of thrust and normal forces showed good correlation. PMID- 27007376 TI - Fast Selective Detection of Pyocyanin Using Cyclic Voltammetry. AB - Pyocyanin is a virulence factor uniquely produced by the pathogen Pseudomonas aeruginosa. The fast and selective detection of pyocyanin in clinical samples can reveal important information about the presence of this microorganism in patients. Electrochemical sensing of the redox-active pyocyanin is a route to directly quantify pyocyanin in real time and in situ in hospitals and clinics. The selective quantification of pyocyanin is, however, limited by other redox active compounds existing in human fluids and by other metabolites produced by pathogenic bacteria. Here we present a direct selective method to detect pyocyanin in a complex electroactive environment using commercially available electrodes. It is shown that cyclic voltammetry measurements between -1.0 V to 1.0 V reveal a potential detection window of pyocyanin of 0.58-0.82 V that is unaffected by other redox-active interferents. The linear quantification of pyocyanin has an R2 value of 0.991 across the clinically relevant concentration range of 2-100 uM. The proposed method was tested on human saliva showing a standard deviation of 2.5% +/- 1% (n = 5) from the known added pyocyanin concentration to the samples. This inexpensive procedure is suggested for clinical use in monitoring the presence and state of P. aeruginosa infection in patients. PMID- 27007378 TI - Physiological Signal Monitoring Bed for Infants Based on Load-Cell Sensors. AB - Ballistocardiographs (BCGs), which record the mechanical activity of the heart, have been a subject of interest for several years because of their advantages in providing unobtrusive physiological measurements. BCGs could also be useful for monitoring the biological signals of infants without the need for physical confinement. In this study, we describe a physiological signal monitoring bed based on load cells and assess an algorithm to extract the heart rate and breathing rate from the measured load-cell signals. Four infants participated in a total of 13 experiments. As a reference signal, electrocardiogram and respiration signals were simultaneously measured using a commercial device. The proposed automatic algorithm then selected the optimal sensor from which to estimate the heartbeat and respiration information. The results from the load cell sensor signals were compared with those of the reference signals, and the heartbeat and respiration information were found to have average performance errors of 2.55% and 2.66%, respectively. The experimental results verify the positive feasibility of BCG-based measurements in infants. PMID- 27007379 TI - A Crowd-Sourcing Indoor Localization Algorithm via Optical Camera on a Smartphone Assisted by Wi-Fi Fingerprint RSSI. AB - Indoor positioning based on existing Wi-Fi fingerprints is becoming more and more common. Unfortunately, the Wi-Fi fingerprint is susceptible to multiple path interferences, signal attenuation, and environmental changes, which leads to low accuracy. Meanwhile, with the recent advances in charge-coupled device (CCD) technologies and the processing speed of smartphones, indoor positioning using the optical camera on a smartphone has become an attractive research topic; however, the major challenge is its high computational complexity; as a result, real-time positioning cannot be achieved. In this paper we introduce a crowd sourcing indoor localization algorithm via an optical camera and orientation sensor on a smartphone to address these issues. First, we use Wi-Fi fingerprint based on the K Weighted Nearest Neighbor (KWNN) algorithm to make a coarse estimation. Second, we adopt a mean-weighted exponent algorithm to fuse optical image features and orientation sensor data as well as KWNN in the smartphone to refine the result. Furthermore, a crowd-sourcing approach is utilized to update and supplement the positioning database. We perform several experiments comparing our approach with other positioning algorithms on a common smartphone to evaluate the performance of the proposed sensor-calibrated algorithm, and the results demonstrate that the proposed algorithm could significantly improve accuracy, stability, and applicability of positioning. PMID- 27007380 TI - An Innovative Optical Sensor for the Online Monitoring and Control of Biomass Concentration in a Membrane Bioreactor System for Lactic Acid Production. AB - Accurate real-time process control is necessary to increase process efficiency, and optical sensors offer a competitive solution because they provide diverse system information in a noninvasive manner. We used an innovative scattered light sensor for the online monitoring of biomass during lactic acid production in a membrane bioreactor system because biomass determines productivity in this type of process. The upper limit of the measurement range in fermentation broth containing Bacillus coagulans was ~2.2 g.L(-1). The specific cell growth rate (u) during the exponential phase was calculated using data representing the linear range (cell density <= 0.5 g.L(-1)). The results were consistently and reproducibly more accurate than offline measurements of optical density and cell dry weight, because more data were gathered in real-time over a shorter duration. Furthermore, u(max) was measured under different filtration conditions (transmembrane pressure 0.3-1.2 bar, crossflow velocity 0.5-1.5 m.s(-1)), showing that energy input had no significant impact on cell growth. Cell density was monitored using the sensor during filtration and was maintained at a constant level by feeding with glucose according to the fermentation kinetics. Our novel sensor is therefore suitable for integration into control strategies for continuous fermentation in membrane bioreactor systems. PMID- 27007381 TI - Integrated (Meta) Genomic and Synthetic Biology Approaches to Develop New Biocatalysts. AB - In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries as a valuable and promising source of novel bioactive compounds. Marine biodiscovery programmes have begun to reveal the extent of novel compounds encoded within the enormous bacterial richness and diversity of the marine ecosystem. A combination of unique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extreme habitats, underscores the potential of the marine environment to deliver on functionally novel biocatalytic activities. With the growing need for green alternatives to industrial processes, and the unique transformations which nature is capable of performing, marine biocatalysts have the potential to markedly improve current industrial pipelines. Furthermore, biocatalysts are known to possess chiral selectivity and specificity, a key focus of pharmaceutical drug design. In this review, we discuss how the explosion in genomics based sequence analysis, allied with parallel developments in synthetic and molecular biology, have the potential to fast-track the discovery and subsequent improvement of a new generation of marine biocatalysts. PMID- 27007382 TI - Preparation and Antitumor Activity of CS5931, A Novel Polypeptide from Sea Squirt Ciona Savignyi. AB - CS5931 is a novel anticancer agent isolated from the sea squirt Ciona savignyi. However, its content in the species is very low, and developing a novel approach for production of the polypeptide is promising. In the present study, we expressed and purified the polypeptide from E. coli, and the fermentation conditions were studied using response surface methodology. The yield of CS5931 was increased from 2.0 to 7.5 mg/L. The denaturing and renaturation conditions were also studied. Using the optimized renaturation condition, the anticancer activity of refolding CS5931 was increased significantly; the value of IC50 was decreased from 23.2 to 11.6 MUM. In vivo study using xenograft nude mice bearing HCT116 cancer cells revealed that CS5931 was able to inhibit the growth of tumor significantly. The study provides a useful approach for obtaining enough amount of CS5931 for further study. This study is also important for developing the polypeptide as a novel anticancer agent. PMID- 27007383 TI - Work-Recreation Balance, Health-Promoting Lifestyles and Suboptimal Health Status in Southern China: A Cross-Sectional Study. AB - Suboptimal health status (SHS)-an intermediate state between health and illness- refers to functional somatic symptoms that are medically undiagnosed. Although- SHS has become a great challenge for global public health, very little about its etiology and mechanisms are known. Work-recreation balance is a part of work-life balance, and is related to stress which greatly influences health status. We therefore carried out a cross-sectional investigation between 2012 and 2013 within a clustered sample of 24,475 individuals aged 15-60 years from a population in southern China. In so doing, we hoped to illuminate the associations between work-recreation balance conditions, healthy lifestyles, and SHS. Work-recreation balance conditions were categorically defined by frequency ("rarely, sometimes, or always"). Health-Promoting Lifestyle Profile (HPLP-II) was used to evaluate the level of healthy lifestyles, and the medical examination report and Sub-Health Measurement Scale V1.0 (SHMS V1.0) were both used to evaluate health status. The ratio of SHS (46.3%) is higher than health status (18.4%) or disease status (35.3%). Overall, 4.9% of respondents reported the lowest level of work-recreation balance, and they scored lower on both the HPLP II and SHMS V1.0 compared with those who frequently maintained a work-recreation balance. Significant association was found between work-recreation balance behaviors and healthy lifestyles (p < 0.001) after demographic adjustment. In comparison with those reporting a frequent work-recreation balance, individuals whose work-recreation balance was categorically "rare" were 1.69 times as likely to develop SHS (odds ratio (OR): 1.69, 95% confidence interval (CI): 1.49-1.92), and those with infrequent work-recreation balance ("sometimes") were 1.71 times more likely to develop SHS (OR: 1.71, 95% CI: 1.62-1.81). These findings suggest that work-recreation balance conditions are significantly associated with, and seem to be accurate behavioral indicia of a healthy lifestyle. Poor work recreation balance is associated with increased risk for SHS; thus, a healthier lifestyle that maintains a work-recreation balance should be promoted in order to reduce the development of SHS or disease in southern China. PMID- 27007384 TI - Effects of Air Pollution on Hospital Emergency Room Visits for Respiratory Diseases: Urban-Suburban Differences in Eastern China. AB - A study on the relationships between ambient air pollutants (PM2.5, SO2 and NO2) and hospital emergency room visits (ERVs) for respiratory diseases from 2013 to 2014 was performed in both urban and suburban areas of Jinan, a heavily air polluted city in Eastern China. This research was analyzed using generalized additive models (GAM) with Poisson regression, which controls for long-time trends, the "day of the week" effect and meteorological parameters. An increase of 10 MUg/m3 in PM2.5, SO2 and NO2 corresponded to a 1.4% (95% confidence interval (CI): 0.7%, 2.1%), 1.2% (95% CI: 0.5%, 1.9%), and 2.5% (95%: 0.8%, 4.2%) growth in ERVs for the urban population, respectively, and a 1.5% (95%: 0.4%, 2.6%), 0.8% (95%: -0.7%, 2.3%), and 3.1% (95%: 0.5%, 5.7%) rise in ERVs for the suburban population, respectively. It was found that females were more susceptible than males to air pollution in the urban area when the analysis was stratified by gender, and the reverse result was seen in the suburban area. Our results suggest that the increase in ERVs for respiratory illnesses is linked to the levels of air pollutants in Jinan, and there may be some urban-suburban discrepancies in health outcomes from air pollutant exposure. PMID- 27007385 TI - Association of Sociodemographic and Perceived Environmental Factors with Public Bicycle Use among Taiwanese Urban Adults. AB - BACKGROUND: This study examined the sociodemographic and perceived environmental factors associated with public bicycle use among Taiwanese urban adults. METHODS: A random-digit-dialing telephone-based cross-sectional survey was administered to Taiwanese urban adults aged 20-64 years in 2015. Data on sociodemographic variables, perceived environmental factors (for attributes identified in the International Physical Activity Questionnaire-Environmental Module), and public bicycle use were obtained from 1002 adults in three cities. Adjusted logistic regression was used. RESULTS: After adjustment for potential confounders, the results showed that adults aged 20-29 years (odds ratio (OR) = 4.42) with a university degree or higher (OR = 2.03) were more likely to use public bicycles. In addition, adults living in Kaohsiung City were less likely to use public bicycles (OR = 0.24). Adults who saw people being active (OR = 1.76; 95% CI: 1.05 2.86) and had positive aesthetic experiences of their environment (OR = 1.69) were more likely to use public bicycles. CONCLUSIONS: Our findings suggest that seeing physically active people and positive aesthetic perceptions of the environment are key factors for developing transportation policies and intervention strategies for promoting public bicycle use among Taiwanese urban adults. PMID- 27007387 TI - EQ-5D-5L in the General German Population: Comparison and Evaluation of Three Yearly Cross-Section Surveys. AB - Health-related quality of life (HRQoL) is a key measure for evaluating health status in populations. Using the recent EQ-5D-5L for measurement, this study analyzed quality of life results and their stability over consecutive population surveys. Three cross-section surveys for representative samples of the general German population from 2012, 2013, and 2014 were evaluated using the EQ-5D-5L descriptive system and valuation by the Visual Analog Scale (VAS). Aggregated sample size reached 6074. The dimension with the highest prevalence of problems was pain/discomfort (31.7%). Compared with 2012 (59.3%), the percentage of participants in the best health state increased slightly in 2013 (63.4%) and 2014 (62%). Over the 3-year period, diabetes and heart disease had the strongest negative influence on mean VAS result. The number of reported chronic diseases cumulatively reduced mean VAS. Extreme problems in one or more dimensions were stated by only 0.1%-0.2% of patients. Of the potential 247 health states with a problem score >= 20, only six were observed in the aggregated sample. HRQoL results were fairly stable over the 3 years, but the share of the population with no problems was not. Results from the aggregated sample may serve as updated reference values for the general German population. PMID- 27007386 TI - Heavy Metal Accumulation is Associated with Molecular and Pathological Perturbations in Liver of Variola louti from the Jeddah Coast of Red Sea. AB - Large amounts of waste water are discharged daily from the Jeddah Metropolitan Area into the Red Sea. Sewage draining into the Red Sea causes widespread chemical pollution that is toxic to aquatic ecosystems. The objective of this study was to investigate the extent of pollution and assess the presence of heavy metals in fish tissue and study their association with biological and biochemical alterations. The average concentrations of heavy metals found in hepatic tissues of Variola louti fish from the polluted area, namely Cd, Cr, Cu, Fe and Zn, were 1.74, 9.69, 47.48, 4020.01 and 229.47 ug/g liver, respectively, that were significantly higher than that of samples taken from reference area (0.24, 1.98, 20.12, 721.93, 129.21 ug/g liver, respectively). The fold change of heavy metals in fish from the polluted area with respect of that of the reference area followed the order Cd > Fe > Cr > Cu > Zn. Analysis of nuclear DNA revealed that hepatic tissues of fish samples from the polluted area showed a significant increase in apoptotic cells as detected by flow cytometry and formation DNA ladder. In addition, hepatic sections from polluted area fishes showed more fibrotic changes and collagen deposition by hematoxylin-eosin staining and Masson's trichrome staining, respectively, compared to samples taken from the reference area. Moreover, the electrophoretic patterns of proteins of liver of fishes caught at the polluted area showed different patterns of proteins from that of the reference with bands at 42, 130 and 140 kDa, which is in a good agreement with the molecular weight of collagen type III. In conclusion, there were significant changes in the tissues of fishes in the polluted area at the cellular and the molecular levels that may be associated with an accumulation of heavy metals. Assessment of fishes as a sensitive biomonitor for the pollution of surface waters that may affect general health of human and wild life is conceivable. PMID- 27007388 TI - Analysis of the Nonlinear Trends and Non-Stationary Oscillations of Regional Precipitation in Xinjiang, Northwestern China, Using Ensemble Empirical Mode Decomposition. AB - Changes in precipitation could have crucial influences on the regional water resources in arid regions such as Xinjiang. It is necessary to understand the intrinsic multi-scale variations of precipitation in different parts of Xinjiang in the context of climate change. In this study, based on precipitation data from 53 meteorological stations in Xinjiang during 1960-2012, we investigated the intrinsic multi-scale characteristics of precipitation variability using an adaptive method named ensemble empirical mode decomposition (EEMD). Obvious non linear upward trends in precipitation were found in the north, south, east and the entire Xinjiang. Changes in precipitation in Xinjiang exhibited significant inter-annual scale (quasi-2 and quasi-6 years) and inter-decadal scale (quasi-12 and quasi-23 years). Moreover, the 2-3-year quasi-periodic fluctuation was dominant in regional precipitation and the inter-annual variation had a considerable effect on the regional-scale precipitation variation in Xinjiang. We also found that there were distinctive spatial differences in variation trends and turning points of precipitation in Xinjiang. The results of this study indicated that compared to traditional decomposition methods, the EEMD method, without using any a priori determined basis functions, could effectively extract the reliable multi-scale fluctuations and reveal the intrinsic oscillation properties of climate elements. PMID- 27007389 TI - Do Climate Change Policies Promote or Conflict with Subjective Wellbeing: A Case Study of Suzhou, China. AB - As public expectations for health rise, health measurements broaden from a focus on death, disease, and disability to wellbeing. However, wellbeing hasn't been incorporated into the framework of climate change policy decision-making in Chinese cities. Based on survey data (n = 763) from Suzhou, this study used Generalized Estimation Equation approach to model external conditions associated with wellbeing. Then, semi-quantitative analyses were conducted to provide a first indication to whether local climate change policies promote or conflict with wellbeing through altering these conditions. Our findings suggested: (i) Socio-demographic (age, job satisfaction, health), psychosocial (satisfaction with social life, ontological security/resilience) and environmental conditions (distance to busy road, noise annoyance and range hoods in the kitchen) were significantly associated with wellbeing; (ii) None of existing climate change strategies in Suzhou conflict with wellbeing. Three mitigation policies (promotion of tertiary and high-tech industry, increased renewable energy in buildings, and restrictions on car use) and one adaption policy (increasing resilience) brought positive co-benefits for wellbeing, through the availability of high-satisfied jobs, reduced dependence on range hoods, noise reduction, and valuing citizens, respectively. This study also provided implications for other similar Chinese cities that potential consequences of climate change interventions for wellbeing should be considered. PMID- 27007390 TI - Predicting the Cytotoxic Potency of Cigarette Smoke by Assessing the Thioredoxin Reductase Inhibitory Capacity of Cigarette Smoke Extract. AB - The present study investigated the influence of the cigarette smoke extract (CSE) on mammalian thioredoxin reductase (TrxR) activity. TrxR is a selenoenzyme with a selenocysteine (Sec) residue exposed on the enzyme's surface. This unique Sec residue is particularly susceptible to modification by numerous types of electrophiles, leading to inactivation of TrxR and consequent cytotoxicity. Cigarette smoke contains various electrophiles, and the present study showed that CSE could inhibit intracellular TrxR through causing crosslinking and alkylation of TrxR1. TrxR inhibitory capacities of various CSEs were evaluated by using mouse-liver homogenate. Among the CSEs prepared from 18 commercial cigarette brands, TrxR inhibitory capacities of the maximum and the minimum had a 2.5-fold difference. Importantly, CSE's inhibitory capacity greatly paralleled its cytotoxic potency in all cell lines used. Compared to cytotoxic assays, which have been widely used for evaluating cigarette toxicity but are not suitable for simultaneously examining a large number of cigarette samples, the present method was simple and rapid with a high-throughput feature and thus could be used as an auxiliary means to predict the cytotoxicity of a large number of cigarette samples, making it possible to extensively screen numerous agricultural and industrial measures that potentially affect cigarette safety. PMID- 27007391 TI - Health Risks Associated with Oil Pollution in the Niger Delta, Nigeria. AB - BACKGROUND: Although there is considerable public concern about the environmental impacts of oil pollution in the Niger Delta of Nigeria, actual evidence on the pathological and psychological effects in the health of local communities is minimally known. We sought to associate the perspective measures of exposure to oil pollution with health outcomes (inventory of health symptoms and functional capacity limitations) and determine how emotional reactions to environmental risks moderate these health outcomes. METHOD: The study was conducted with 600 participants selected from five local government areas in Akwa Ibom State where oil pollution is rampant. A structured questionnaire was used to collect the data on the respondents' exposure to oil pollution, self-rated health and disease symptoms, perception of risk of exposure and emotional reactions to local oil pollution. RESULTS: Most of the participants lived in areas with visible oil pollution and/or near gas flaring facilities and regularly suffered direct exposure to oil in their environment. High level of emotional distress was a part of everyone's life for the study population. Risk perception in the study area was mediated, to a large extent, by dreaded hazards (catastrophic fears of pipeline explosions and oil spill fire), visual cues (gas flares and smoke stacks) and chemosensory cues (off-flavor in drinking water). The exposure metrics were found to be significant predictors of the health effects and influencing factors (emotional reactions). Multi-levels models suggest that at the individual level, the demographic variables and direct contact with oil pollution were important mediators of functional capacity limitation. At the community level, emotional distress from fear of the sources of exposure was an important mediator of the health symptoms. CONCLUSIONS: This study documents high levels of disease symptoms and environmental distress (worry, annoyance and intolerance) associated with oil pollution in the Niger Delta areas of Nigeria. It highlights the need for some intervention to ameliorate the psychological distress associated with living under such environmental adversity. PMID- 27007392 TI - n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease. AB - DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients. PMID- 27007393 TI - Gender Differences in Response to Prolonged Every-Other-Day Feeding on the Proliferation and Apoptosis of Hepatocytes in Mice. AB - Intermittent fasting decreases glucose and insulin levels and increases insulin sensitivity and lifespan. Decreased food intake influences the liver. Previous studies have shown gender differences in response to various types of caloric restriction, including every-other-day (EOD) feeding, in humans and rodents. Our goal was to show the influence of prolonged EOD feeding on the morphology, proliferation and apoptosis of livers from male and female mice. After nine months of an EOD diet, the livers from male and female mice were collected. We examined their morphology on histological slides using the Hematoxilin and Eosine (H_E) method and Hoechst staining of cell nuclei to evaluate the nuclear area of hepatocytes. We also evaluated the expression of mRNA for proto-oncogens, pro survival proteins and apoptotic markers using Real Time Polimerase Chain Reaction (PCR). We noted increased lipid content in the livers of EOD fed female mice. EOD feeding lead to a decrease of proliferation and apoptosis in the livers of female and male mice, which suggest that tissue maintenance occurred during EOD feeding. Our experiment revealed sex-specific expression of mRNA for proto-oncogenes and pro-survival and pro-apoptotic genes in mice as well as sex-specific responses to the EOD treatment. PMID- 27007394 TI - Ochratoxin A Producing Fungi, Biosynthetic Pathway and Regulatory Mechanisms. AB - Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked with l-phenylalanine via an amide bond. OTA biosynthesis has been putatively hypothesized, although several contradictions exist on some processes of the biosynthetic pathway. We discuss recent information on molecular studies of OTA biosynthesis despite insufficient genetic background in detail. Accordingly, genetic regulation has also been explored with regard to the interaction between the regulators and the environmental factors. In this review, we focus on three aspects of OTA: OTA-producing strains, OTA biosynthetic pathway and the regulation mechanisms of OTA production. This can pave the way to assist in protecting food and feed from OTA contamination by understanding OTA biosynthetic pathway and regulatory mechanisms. PMID- 27007396 TI - Simultaneous Novel Mutations of LRP5 and TSPAN12 in a Case of Familial Exudative Vitreoretinopathy. AB - Familial exudative vitreoretinopathy and osteoporosis pseudoglioma syndrome are conditions that result from mutations in the LRP5 gene. Persistent fetal vasculature is a rare congenital malformation that can mimic end-stage familial exudative vitreoretinopathy. The authors report a case of familial exudative vitreoretinopathy in the spectrum of osteoporosis pseudoglioma syndrome associated with novel mutations of the LRP5 and TSPAN12 genes that resulted in a phenotype similar to bilateral persistent fetal vasculature. Both conditions can result in bilateral early-onset blindness. A high index of suspicion, dilated fundus examination and angiography of the parents, and genetic testing are necessary to ensure a correct diagnosis. PMID- 27007395 TI - Gastrointestinal Degradation of Fumonisin B1 by Carboxylesterase FumD Prevents Fumonisin Induced Alteration of Sphingolipid Metabolism in Turkey and Swine. AB - The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed and causes various adverse health effects in domestic animals. Hence, effective strategies are needed to prevent the impact of fumonisins on livestock productivity. Here we evaluated the capability of the fumonisin carboxylesterase FumD to degrade FB1 to its less toxic metabolite hydrolyzed FB1 (HFB1) in the gastrointestinal tract of turkeys and pigs. First, an ex vivo pig model was used to examine the activity of FumD under digestive conditions. Within 2 h of incubation with FumD, FB1 was completely degraded to HFB1 in the duodenum and jejunum, respectively. To test the efficacy of the commercial application of FumD (FUMzyme) in vivo, female turkeys (n = 5) received either basal feed (CON), fumonisin-contaminated feed (15 mg/kg FB1+FB2; FB) or fumonisin-contaminated feed supplemented with FUMzyme (15 U/kg; FB+FUMzyme) for 14 days ad libitum. Addition of FUMzyme resulted in significantly decreased levels of FB1 in excreta, whereas HFB1 concentrations were significantly increased. Compared to the FB group (0.24 +/- 0.02), the mean serum sphinganine-to-sphingosine (Sa/So) ratio was significantly reduced in the FB+FUMzyme group (0.19 +/- 0.02), thus resembling values of the CON group (0.16 +/- 0.02). Similarly, exposure of piglets (n = 10) to 2 mg/kg FB1+FB2 for 42 days caused significantly elevated serum Sa/So ratios (0.39 +/- 0.15) compared to the CON group (0.14 +/- 0.01). Supplementation with FUMzyme (60 U/kg) resulted in gastrointestinal degradation of FB1 and unaffected Sa/So ratios (0.16 +/- 0.02). Thus, the carboxylesterase FumD represents an effective strategy to detoxify FB1 in the digestive tract of turkeys and pigs. PMID- 27007397 TI - Fabricated or Induced Illness Presenting as Recurrent Corneal Lesions, Cataracts, and Uveitis. AB - Two siblings with ophthalmic findings, psychomotor retardation, somnolence, and seizures underwent diagnostic studies, genetic investigations, ultrasonography, biomicroscopy, and posterior and anterior optical coherence tomography. Both siblings experienced eye problems at different times from the age of 6 months to 12 years. The family pedigree and neurological problems (ie, hypotony, seizures, sleepiness, and speech and psychomotor delay) suggested a metabolic or mitochondrial pathology. After exclusion of multiple potential diseases, a fabricated or induced illness was suspected. Fabricated or induced illness can be a cause for unusual clinical findings and should be considered in the differential diagnosis when ocular and other abnormalities cannot be explained after a comprehensive evaluation. The diagnosis of fabricated or induced illness should not be based on exclusion alone but rather on positive findings. PMID- 27007398 TI - Liver Failure in Early Infancy: Aetiology, Presentation, and Outcome. AB - OBJECTIVE: Acute liver failure (ALF) in early infancy is rare and challenging to recognize and manage. We aim to describe the presentation and outcome of infants with ALF according to their final aetiology to elucidate features to facilitate early recognition leading to prompt diagnosis and management. METHODS: All infants presenting within 120 days from birth with liver failure were included in a retrospective review over a 19-year period. The aetiology, clinical features, presenting investigations, and outcome were collected. RESULTS: Seventy-eight young infants presented with ALF. The aetiology was established in 94% and included metabolic disease (36%), hypoxic-ischaemic (HI) insult (19%), infection (17%), neonatal haemochromatosis (9%), and infiltrative disease (9%). Infections, infiltrative disease, and acute HI insult usually resulted in higher transaminases and international normalized ratio, whereas neonatal haemochromatosis and tyrosinaemia were characterized by lower or near normal transaminases. Overall jaundice was not visible in 24% of infants at presentation. Forty-five (58%) infants were alive at discharge from hospital. Survival at 1 year was 53% and survival with native liver 50%. Later deaths occurred in infants with mitochondrial disease. Six infants received a liver transplant and 4 subsequently died from their underlying disease. CONCLUSION: ALF should be considered in any young infant with a coagulopathy as transaminases and/or bilirubin levels can be near normal at presentation. Better intensive care and the judicious use of liver transplantation may have contributed to the improved outcomes for this group compared with previous decades. PMID- 27007399 TI - Central Liver Nodules in Alagille Syndrome and Biliary Atresia After Kasai Portoenterostomy. PMID- 27007400 TI - The Changing Spectrum of Neonatal Hepatitis. PMID- 27007401 TI - Mutation in Actin gamma-2 Responsible for Megacystis Microcolon Intestinal Hypoperistalsis Syndrome in 4 Chinese Patients. AB - The aim of this study was to identify the underlying molecular mechanism for the development of megacystis microcolon intestinal hypoperistalsis syndrome in 4 Chinese patients. We found a c.770G>A (p.R257H) mutation in 3 patients, and a c.769C>T (p.R257C) mutation in the fourth patient by using whole-exome sequencing and targeted Sanger sequencing. The immunohistochemical investigation and transmission electron microscopy revealed an apparent defect of the intestinal smooth muscle, and hypoganglionosis. Our report suggested that R257 variant in the ACTG2 appear to be more frequent in populations of Asian ancestry; mutation of this locus could cause alterations of the intestinal and bladder smooth muscle filaments. PMID- 27007402 TI - Distinct Effects of Estrogen on Mouse Maternal Behavior: The Contribution of Estrogen Synthesis in the Brain. AB - Estrogen surge following progesterone withdrawal at parturition plays an important role in initiating maternal behavior in various rodent species. Systemic estrogen treatment shortens the latency to onset of maternal behavior in nulliparous female rats that have not experienced parturition. In contrast, nulliparous laboratory mice show rapid onset of maternal behavior without estrogen treatment, and the role of estrogen still remains unclear. Here the effect of systemic estrogen treatment (for 2 h, 1 day, 3 days, and 7 days) after progesterone withdrawal was examined on maternal behavior of C57BL/6 mice. This estrogen regimen led to different effects on nursing, pup retrieval, and nest building behaviors. Latency to nursing was shortened by estrogen treatment within 2 h. Moreover, pup retrieval and nest building were decreased. mRNA expression was also investigated for estrogen receptor alpha (ERalpha) and for genes involved in regulating maternal behavior, specifically, the oxytocin receptor (OTR) and vasopressin receptor in the medial amygdala (MeA) and medial preoptic area (MPOA). Estrogen treatment led to decreased ERalpha mRNA in both regions. Although OTR mRNA was increased in the MeA, OTR and vasopressin receptor mRNA were reduced in the MPOA, showing region-dependent transcription regulation. To determine the mechanisms for the actions of estrogen treatment, the contribution of estrogen synthesis in the brain was examined. Blockade of estrogen synthesis in the brain by systemic letrozole treatment in ovariectomized mice interfered with pup retrieval and nest building but not nursing behavior, indicating different contributions of estrogen synthesis to maternal behavior. Furthermore, letrozole treatment led to an increase in ERalpha mRNA in the MeA but not in the MPOA, suggesting that involvement of estrogen synthesis is brain region dependent. Altogether, these results suggest that region-dependent estrogen synthesis leads to differential transcriptional activation due to exogenous estrogen treatment, and thereby results in different effects on maternal behavior. PMID- 27007403 TI - Coagulation is more affected by quick than slow bleeding in patients with massive blood loss. AB - Profuse blood loss affects blood coagulation to various degrees. However, whether bleeding speed affects coagulation remains uncertain. This study aimed to evaluate the effect of bleeding speed on coagulation function. A total of 141 patients in the Department of Thoracic Surgery of our hospital were evaluated between January 2007 and February 2014. There are two groups of patients, those who received decortication for chronic encapsulated empyema were called the slow bleeding group, and those who received thoracoscopic upper lobectomy were called the fast bleeding group; each group was further subdivided into three: group A, 1000 ml <= bleeding amount < 1500 ml; group B, 1500 ml <= bleeding amount < 1700 ml; group C, 1700 ml <= bleeding amount < 2000 ml. Then, coagulation function was assessed in all patients before and during surgery and at 1, 2, and 24 h after surgery, measuring prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, blood pressure, hematocrit, hemoglobin, and platelets. Bleeding duration was overtly longer in the slow-bleeding group than that in quick bleeding individuals (2.3 +/- 0.25 h vs. 0.41 +/- 0.13 h, P < 0.001). Fibrinogen, hematocrit, hemoglobin, and platelets strikingly decreased, whereas prothrombin time and APTT values significantly increased with bleeding amounts in both quick and slow-bleeding groups. Interestingly, compared with slow-bleeding patients, coagulation indices at each time point and bleeding amounts had significant differences in the quick bleeding group.Increased consumption of coagulation factors in quick bleeding may have greater impact on coagulation function. PMID- 27007404 TI - Painful Perianal Papules in a Middle-Aged Woman. PMID- 27007405 TI - Views of US Voters on Compensating Living Kidney Donors. AB - IMPORTANCE: Patients in the United States waiting for kidney transplantation die in increasing numbers owing to the severe kidney shortage, which might be alleviated by compensating living kidney donors. OBJECTIVE: To determine the willingness of voting US citizens to become living kidney donors and to ascertain the potential influence of compensation for donation. DESIGN, SETTING, AND PARTICIPANTS: A professionally designed quantitative survey was administered by an international polling firm in June 2014. Information was collected on willingness to donate a kidney and the potential influence of compensation ($50 000); survey data included respondent age, income, education level, sex, US region, race/ethnicity, marital status, political affiliation, likelihood to vote, and employment status. The survey was performed via a random-digit dialing process that selected respondents via both landlines and mobile telephones to improve population representation. The survey included 1011 registered US voters likely to vote. MAIN OUTCOMES AND MEASURES: The degree to which the US voting public is willing to donate a kidney and the perceptions of current voters toward paying living kidney donors. RESULTS: Of the 1011 respondents, 427 were male and 584 were female, with 43% of participants between ages 45 and 64 years. With respondents grouped by willingness to donate, we found that 689 (68%) would donate a kidney to anyone and 235 (23%) only to certain persons; 87 (9%) would not donate. Most (59%) indicated that payment of $50 000 would make them even more likely to donate a kidney, 32% were unmoved by compensation, and 9% were negatively influenced by payment. CONCLUSIONS AND RELEVANCE: Most US voters view living kidney donation positively, and most would be motivated toward donor nephrectomy if offered a payment of $50 000. Because most registered voters favor such payments, and because thousands of lives might be saved should compensation increase the number of transplantable kidneys, laws and regulations prohibiting donor compensation should be modified to allow pilot studies of financial incentives for living kidney donors. Outcomes of such trials could then result in evidence-based policies, which would incorporate fair and just compensation to those persons willing to undergo donor nephrectomy. PMID- 27007406 TI - Novel Approaches for the Interim Management of Relapsed/Refractory Acute Lymphocytic Leukemia: A Case-Study Compendium. AB - The heterogeneous hematologic malignancy acute lymphocytic leukemia (ALL) represents one of the more complicated cancers in adults. Despite the large number of agents available to treat this disease, there remains no standard of care for either the frontline or relapsed/refractory settings. Although the rate of response to initial induction therapy is high, at least half of patients experience relapsed or refractory disease. Selection of salvage therapy may rely on investigational strategies in clinical trials. The goal of frontline or salvage therapy is to reduce the tumor burden so that patients can proceed to allogeneic stem cell transplant, the only treatment considered potentially curative for ALL. However, the different combination chemotherapy regimens are associated with unpredictable responses and can result in myelosuppression and other toxicities. The need for improved treatment alternatives, especially in the salvage setting, has been recently addressed with the introduction of several new therapies. Chimeric antigen receptor (CAR) T-cell therapy is a form of immunotherapy. T cells harvested from the patient are genetically engineered to express a receptor that targets a tumor-specific antigen on the tumor cell surface. Patients awaiting CAR T-cell therapy, like those awaiting stem cell transplant, often require a "bridge" treatment during the interim. A liposomal formulation of vincristine has been associated with durable responses in relapsed disease, but with less myelosuppression and neurotoxicity than standard vincristine. Other novel agents include blinatumomab and inotuzumab ozogamicin. PMID- 27007411 TI - Digestion of Yeasts and Beta-1,3-Glucanases in Mosquito Larvae: Physiological and Biochemical Considerations. AB - Aedes aegypti larvae ingest several kinds of microorganisms. In spite of studies regarding mosquito digestion, little is known about the nutritional utilization of ingested cells by larvae. We investigated the effects of using yeasts as the sole nutrient source for A. aegypti larvae. We also assessed the role of beta-1,3 glucanases in digestion of live yeast cells. Beta-1,3-glucanases are enzymes which hydrolyze the cell wall beta-1,3-glucan polyssacharide. Larvae were fed with cat food (controls), live or autoclaved Saccharomyces cerevisiae cells and larval weight, time for pupation and adult emergence, larval and pupal mortality were measured. The presence of S. cerevisiae cells inside the larval gut was demonstrated by light microscopy. Beta-1,3-glucanase was measured in dissected larval samples. Viability assays were performed with live yeast cells and larval gut homogenates, with or without addition of competing beta-1,3-glucan. A. aegypti larvae fed with yeast cells were heavier at the 4th instar and showed complete development with normal mortality rates. Yeast cells were efficiently ingested by larvae and quickly killed (10% death in 2 h, 100% in 48 h). Larvae showed beta-1,3-glucanase in head, gut and rest of body. Gut beta-1,3-glucanase was not derived from ingested yeast cells. Gut and rest of body activity was not affected by the yeast diet, but head homogenates showed a lower activity in animals fed with autoclaved S. cerevisiae cells. The enzymatic lysis of live S. cerevisiae cells was demonstrated using gut homogenates, and this activity was abolished when excess beta-1,3-glucan was added to assays. These results show that live yeast cells are efficiently ingested and hydrolyzed by A. aegypti larvae, which are able to fully-develop on a diet based exclusively on these organisms. Beta-1,3-glucanase seems to be essential for yeast lytic activity of A. aegypti larvae, which possess significant amounts of these enzyme in all parts investigated. PMID- 27007412 TI - Fracture and adhesion of soft materials: a review. AB - Soft materials are materials with a low shear modulus relative to their bulk modulus and where elastic restoring forces are mainly of entropic origin. A sparse population of strong bonds connects molecules together and prevents macroscopic flow. In this review we discuss the current state of the art on how these soft materials break and detach from solid surfaces. We focus on how stresses and strains are localized near the fracture plane and how elastic energy can flow from the bulk of the material to the crack tip. Adhesion of pressure sensitive-adhesives, fracture of gels and rubbers are specifically addressed and the key concepts are pointed out. We define the important length scales in the problem and in particular the elasto-adhesive length Gamma/E where Gamma is the fracture energy and E is the elastic modulus, and how the ratio between sample size and Gamma/E controls the fracture mechanisms. Theoretical concepts bridging solid mechanics and polymer physics are rationalized and illustrated by micromechanical experiments and mechanisms of fracture are described in detail. Open questions and emerging concepts are discussed at the end of the review. PMID- 27007410 TI - Effects of Plectin Depletion on Keratin Network Dynamics and Organization. AB - The keratin intermediate filament cytoskeleton protects epithelial cells against various types of stress and is involved in fundamental cellular processes such as signaling, differentiation and organelle trafficking. These functions rely on the cell type-specific arrangement and plasticity of the keratin system. It has been suggested that these properties are regulated by a complex cycle of assembly and disassembly. The exact mechanisms responsible for the underlying molecular processes, however, have not been clarified. Accumulating evidence implicates the cytolinker plectin in various aspects of the keratin cycle, i.e., by acting as a stabilizing anchor at hemidesmosomal adhesion sites and the nucleus, by affecting keratin bundling and branching and by linkage of keratins to actin filament and microtubule dynamics. In the present study we tested these hypotheses. To this end, plectin was downregulated by shRNA in vulvar carcinoma-derived A431 cells. As expected, integrin beta4- and BPAG-1-positive hemidesmosomal structures were strongly reduced and cytosolic actin stress fibers were increased. In addition, integrins alpha3 and beta1 were reduced. The experiments furthermore showed that loss of plectin led to a reduction in keratin filament branch length but did not alter overall mechanical properties as assessed by indentation analyses using atomic force microscopy and by displacement analyses of cytoplasmic superparamagnetic beads using magnetic tweezers. An increase in keratin movement was observed in plectin-depleted cells as was the case in control cells lacking hemidesmosome-like structures. Yet, keratin turnover was not significantly affected. We conclude that plectin alone is not needed for keratin assembly and disassembly and that other mechanisms exist to guarantee proper keratin cycling under steady state conditions in cultured single cells. PMID- 27007413 TI - An Application of Bayesian Approach in Modeling Risk of Death in an Intensive Care Unit. AB - BACKGROUND AND OBJECTIVES: There are not many studies that attempt to model intensive care unit (ICU) risk of death in developing countries, especially in South East Asia. The aim of this study was to propose and describe application of a Bayesian approach in modeling in-ICU deaths in a Malaysian ICU. METHODS: This was a prospective study in a mixed medical-surgery ICU in a multidisciplinary tertiary referral hospital in Malaysia. Data collection included variables that were defined in Acute Physiology and Chronic Health Evaluation IV (APACHE IV) model. Bayesian Markov Chain Monte Carlo (MCMC) simulation approach was applied in the development of four multivariate logistic regression predictive models for the ICU, where the main outcome measure was in-ICU mortality risk. The performance of the models were assessed through overall model fit, discrimination and calibration measures. Results from the Bayesian models were also compared against results obtained using frequentist maximum likelihood method. RESULTS: The study involved 1,286 consecutive ICU admissions between January 1, 2009 and June 30, 2010, of which 1,111 met the inclusion criteria. Patients who were admitted to the ICU were generally younger, predominantly male, with low co morbidity load and mostly under mechanical ventilation. The overall in-ICU mortality rate was 18.5% and the overall mean Acute Physiology Score (APS) was 68.5. All four models exhibited good discrimination, with area under receiver operating characteristic curve (AUC) values approximately 0.8. Calibration was acceptable (Hosmer-Lemeshow p-values > 0.05) for all models, except for model M3. Model M1 was identified as the model with the best overall performance in this study. CONCLUSION: Four prediction models were proposed, where the best model was chosen based on its overall performance in this study. This study has also demonstrated the promising potential of the Bayesian MCMC approach as an alternative in the analysis and modeling of in-ICU mortality outcomes. PMID- 27007414 TI - UNIVERSITY OF SAO PAULO SCHOOL OF NURSING: a world-class school. PMID- 27007415 TI - [Opportunistic screening actions for breast cancer performed by nurses working in primary health care]. AB - OBJECTIVE: To identify opportunistic screening actions for breast cancer performed by nurses working in primary health care units in Ribeirao Preto, Sao Paulo. METHOD: Cross-sectional study with 60 nurses from 28 units, who had been working for at least one year in the public municipal health care network. Data were collected between December 2013 and March 2014, by means of a questionnaire, using descriptive analysis and the software IBM SPSS version 20 and Microsoft Excel 2010. RESULTS: The results showed that 71.7% of the participants questioned their female patients as for risk factors for breast cancer, mainly during nursing consultation; 70.0% oriented users about the age to perform clinical breast exam, whereas 30.0% did not due to lack of knowledge and time; 60.0% explained about the age to perform mammogram; 73.3% did not refer patients with suspicious breast exam results to the referral department, citing scheduling as the main obstacle to referral. Educational activities were not performed by 78.3% of participants. CONCLUSION: Investment is needed in professional training and management of breast cancer screening. PMID- 27007416 TI - [Incidence of local complications and risk factors associated with peripheral intravenous catheter in neonates]. AB - OBJECTIVE: To evaluate the incidence of complications related to the use of peripheral intravenous catheter in neonates and identify the associated risk factors. METHOD: Prospective cohort study conducted in a Neonatal Intensive Care Unit. Participants were the hospitalized neonates undergoing peripheral intravenous puncture in the period from February to June 2013. RESULTS: The incidence of complications was 63.15%, being infiltration/extravasation (69.89%), phlebitis (17.84%) and obstruction (12.27%). The risk factors were the presence of infection (p = 0.0192) and weight at the puncture day (p = 0.0093), type of intermittent infusion associated with continuous infusion (p <0.0001), endotracheal intubation (p = 0.0008), infusion of basic plan (p = 0.0027), total parenteral nutrition (P = 0.0002), blood transfusion associated with other infusions (p = 0.0003) and other drugs (p = 0.0004). Higher risk of developing complications in the first 48 hours after puncture. CONCLUSION: A high rate of complications related to the use of peripheral intravenous catheter, and risk factors associated with infection, weight, drugs and infused solutions, and type of infusion. PMID- 27007417 TI - [Factors associated with involuntary hospital admissions in technology-dependent children]. AB - OBJECTIVE: To identify the factors associated with involuntary hospital admissions of technology-dependent children, in the municipality of Ribeirao Preto, Sao Paulo State, Brazil. METHOD: A cross-sectional study, with a quantitative approach. After an active search, 124 children who qualified under the inclusion criteria, that is to say, children from birth to age 12, were identified. Data was collected in home visits to mothers or the people responsible for the children, through the application of a questionnaire. Analysis of the data followed the assumptions of the Generalized Linear Models technique. RESULTS: 102 technology-dependent children aged between 6 months and 12 years participated in the study, of whom 57% were male. The average number of involuntary hospital admissions in the previous year among the children studied was 0.71 (+/-1.29). In the final model the following variables were significantly associated with the outcome: age (OR=0.991; CI95%=0.985-0.997), and the number of devices (OR=0.387; CI95%=0.219-0.684), which were characterized as factors of protection and quantity of medications (OR=1.532; CI95%=1.297-1.810), representing a risk factor for involuntary hospital admissions in technology dependent children. CONCLUSION: The results constitute input data for consideration of the process of care for technology-dependent children by supplying an explanatory model for involuntary hospital admissions for this client group. PMID- 27007418 TI - [Mothers' perceptions of care practices for children who underwent heart transplantation]. AB - OBJECTIVE: To learn mothers' perceptions of the main care practices that are to be administered after their children's heart transplantation, as well as the main difficulties they experience. METHOD: A descriptive qualitative study conducted in March and April 2014, using the focus group technique for data gathering. Participants were 12 mothers who were monitoring their children in a hospital that is a reference for treating cardiopulmonary diseases. Speeches were recorded, transcribed, and organized around the care practices that the mothers performed after the children's heart transplantations, the mothers' main difficulties, their perceptions of their children's quality of life, and the use of educational materials to disseminate post-transplantation care practices. For data analysis, we used the content analysis technique. RESULTS: The following were clarified: the schedule of immunosuppressive medication; food, environmental, and bodily and oral hygiene; the use of surgical masks; and keeping the children away from crowds. CONCLUSION: The study contributed to the situational diagnosis of the care administered by the mothers of transplanted children. PMID- 27007420 TI - [The control of hypertension in men and women: a comparative analysis]. AB - OBJECTIVE: To compare men and women who have hypertension with reference to the following: high blood pressure, biosocial variables, habits and life styles, mental disorders, and social support networks. METHOD: 290 hypertensive patients (women, 62.1%) were evaluated. The assessments involved the following: measuring blood pressure with an automatic measuring device, evaluating social status through the Social Support Scale, and the use of a Self-Report Questionnaire (SRQ 20) to identify common mental disorders. A value of p<0.05 was considered statistically significant. RESULTS: Women were found to be different to men (p<0.05) in the following areas having: better control of their blood pressure (64.4% vs 52.7%), less salary incomes, less diabetes, higher total cholesterol, higher body mass index and wider abdominal circumferences. They also had lower systolic blood pressure, lower levels of alcohol consumption and a greater prevalence for mental disorders. The social support assessment revealed that hypertensive women received less help with preparing meals but had more company from people which allowed them to engage in enjoyable activities. CONCLUSION: Women had more control over their blood pressure than men, despite the presence of negative biopsychosocial factors that may have influenced their adherence to the treatments. PMID- 27007419 TI - [Surgical site infection and its risk factors in colon surgeries]. AB - OBJECTIVE: To identify the occurrence of surgical site infection (SSI) and its risk factors in patients undergoing colon surgery in a tertiary hospital located in the countryside of the state of Sao Paulo. METHOD: Retrospective cohort study, with collection of information contained in the medical records of patients undergoing colon surgery in the period between January 2010 and December 2013. The studied variables were the possible risk factors related to the patient, to demographic characteristics and the surgical procedure. RESULTS: In total, were evaluated 155 patients with an overall SSI incidence of 16.7%. A statistically significant association was found both in the univariate as in the multivariate analysis between the SSI and the following variables: male gender, Charlson index and mechanical bowel preparation. CONCLUSION: The understanding of health professionals about the factors that influence the incidence of SSI in colon surgery may contribute to the quality of care provided to surgical patients, from effective actions to minimize the risk of infections. PMID- 27007421 TI - [Relationship between the users' contact time in educational programs on diabetes mellitus and self-care skills and knowledge]. AB - OBJECTIVE: Check the relationship between the users' contact time in educational programs and self-care and knowledge variables in diabetes mellitus. METHOD: A longitudinal study with a quantitative approach with the participation, in the initial phase, of 263 users linked to Basic Health Units in Belo Horizonte, Brazil during the years 2012 and 2013. The data were collected with respect to the total contact time of the users' participation in the educational program as regards knowledge and self-care in acquired diabetes mellitus. The data were analyzed using the Student t-test for comparison of means, considering a 0.05 significance level. RESULTS: The final sample included 151 users. The analysis showed that the improvement in self-care scores was statistically higher during an educational intervention of eight hours or more (p-value <0.05). In relation to the scores for knowledge, there was a statistically significant improvement at the end of the educational program. It was not possible to identify a value for the contact time from which there was an increase in mean scores for the ability of knowledge. CONCLUSION: To improve the effectiveness of the promotion of skills related to knowledge and self-care in diabetes mellitus, it is necessary to consider the contact time as a relevant factor of the educational program. PMID- 27007422 TI - [The psychosocial impacts caused by diagnosis and treatment of Coeliac Disease]. AB - OBJECTIVE: To comprehend the psychosocial effects that Coeliac Disease diagnosis entails. METHOD: Qualitative study, achieved through semi-structured interviews, analyzed in accordance to the Association of ideas map Technique. A total 12 recently-diagnosed patients from the Centro de diagnostico, tratamento e apoio ao paciente com doenca celiaca (Coeliac Disease Prevention, Support and Treatment Diagnose Centre) from the Hospital Universitario de Brasilia (University Hospital of Brasilia) were enrolled for the study, between the years of 2013 and 2014. RESULTS: The interviewed patients presented negative impacts in three categories: psychoaffective, family and social relationships, indicating issues with social readaptation once the treatment had started, as well as difficulty coping with a gluten free diet. CONCLUSION: Coeliac Disease holds substantial impact on psychological functions, family and social relationships to diagnosed patients, requiring a clinical biopsychological assistance for better adherence to treatment and patients quality of life. PMID- 27007423 TI - [Understanding unsuccessful attempts to quit smoking: a social phenomenology approach]. AB - OBJECTIVE: The aim of this paper is to understand the experience of smokers in view of unsuccessful attempts to quit smoking. METHOD: This study is based on social phenomenology. Between November and December of 2014, nine interviews were conducted with people that had attempted to quit smoking. The content of these interviews was analyzed and discussed based on the related literature. RESULTS: Unsuccessful attempts to quit smoking are related to tobacco addiction; cigarettes are seen as a support to cope with everyday stressful situations. Attempts to quit the smoking habits were based on the need of health improvement and insistence of family and friends. Smokers reported the use of habit cessation strategies learned in support groups, but they also express expectation of specialized psychological support. CONCLUSION: The study points out the need to expand the strategies of approaching smokers, and reinforcing psychological support in order to achieve success in the attempt to quit smoking. PMID- 27007424 TI - [Social representation of Alzheimer's disease for family caregivers: stressful and rewarding]. AB - OBJECTIVE: To understand the content of Social Representation (SR) of family caregivers of Alzheimer's disease patients. METHOD: Interviews were conducted with 26 caregivers and analyzed by the ALCESTE software. RESULTS: The SR content was structured in two thematic axes called Daily Life and Care and Medical and Emotional Concepts and Outcomes. The first axis creates images related to the routine of interaction with the sick person, and contains a description of care procedures, experiences, and practices applied every day. The second is composed of subjective and conceptual aspects that make up the social representation of Alzheimer's disease, with meanings related to the emotional, medical, and biological contexts. CONCLUSION: Due to the importance of topics related to patients' dependence and the personal and emotional consequences of the disease, overload is the main content of the SR of Alzheimer's disease for caregivers, and the understanding of these SR by health professionals should support the planning of interventions addressing this group of individuals. PMID- 27007425 TI - [Handgrip strength and physical activity in frail elderly]. AB - OBJECTIVE: To investigate the association between handgrip strength (HS) and physical activity in physical frailty elderly. METHOD: Cross-sectional quantitative study with a sample of 203 elderly calculated based on the population estimated proportion. Tests were applied to detect cognitive impairment and assessment of physical frailty. Descriptive statistics and multivariate analysis by binary logistic regression were used, and also Student's t-test and Fisher's exact test. RESULTS: A total of 99 (64.3%) elderly showed decreased handgrip strength and 90 (58.4%) elderly presented decrease in physical activity levels. There was a statistically significant difference between these two components (p=0.019), in which elderly who have decreased HS have lower levels of physical activity. For low levels of physical activity and decreased HS, there was no evidence of significant difference in the probability of the classification as frail elderly (p<0.001). CONCLUSION: The components handgrip strength and physical activity are associated with the frail elderly. The joint presence of low levels of physical activity and decreased handgrip strength leads to a significantly higher probability of the elderly to be categorized as frailty. PMID- 27007426 TI - [Workloads and strain process in Community Health Agents]. AB - OBJECTIVE: To identify the workloads present in the work activities of community health agents (CHAs) and the resulting strain processes. METHOD: A descriptive, exploratory, cross-sectional and quantitative study conducted with 137 CHAs. Data were collected through a questionnaire and interview guided by the health surveillance software called SIMOSTE (Health Monitoring System of Nursing Workers), following the ethical codes of the current law. RESULTS: In total, were identified 140 workloads involved in 122 strain processes, represented by the occurrence of health problems of the CHAs. The mechanical (55.00%) and biological (16.43%) loads stood out. The most common strain processes were the external causes of morbidity and mortality (62.31%) and diseases of the musculoskeletal system and connective tissue (10.66%). CONCLUSION: From the identified overloads, it became evident that all workloads are present in the work process of CHAs, highlighting the mechanical load, represented mainly by external causes of morbidity and mortality that are related to occupational accidents. PMID- 27007427 TI - [Cost of nursing turnover in a Teaching Hospital]. AB - OBJECTIVE: To map the sub processes related to turnover of nursing staff and to investigate and measure the nursing turnover cost. METHOD: This is a descriptive exploratory study, classified as case study, conducted in a teaching hospital in the southeastern, Brazil, in the period from May to November 2013. The population was composed by the nursing staff, using Nursing Turnover Cost Calculation Methodology. RESULTS: The total cost of turnover was R$314.605,62, and ranged from R$2.221,42 to R$3.073,23 per employee. The costs of pre-hire totaled R$101.004,60 (32,1%), and the hiring process consumed R$92.743,60 (91.8%) The costs of post-hire totaled R$213.601,02 (67,9%), for the sub process decreased productivity, R$199.982,40 (93.6%). CONCLUSION: The study identified the importance of managing the cost of staff turnover and the financial impact of the cost of the employee termination, which represented three times the average salary of the nursing staff. PMID- 27007428 TI - [Informatics competencies essential to decision making in nursing management]. AB - OBJECTIVE: To identify informatics abilities essential to decision making in nursing management. METHOD: Survey study with specialist nurses in health informatics and management. An electronic questionnaire was built based on the competencies Information Literacy (five categories; 40 abilities) and Information Management (nine categories; 69 abilities) of the TIGER - Technology Informatics Guiding Education Reform - initiative, with the guiding question: Which informatics abilities are essential to decision making in management? Answers were sorted in a Likert scale, ranging from 1 to 5. Rasch analysis was conducted with the software WINSTEPS((r)). Results were presented in logits, with cutoff value zero. RESULTS: Thirty-two specialists participated, coming from all regions of Brazil. In the information literacy competency, 18 abilities were considered essential and in Information Management, 38; these were sorted according to their degree of essentiality. CONCLUSION: It is believed that the incorporation of these abilities in teaching can support the education of nurse managers and contribute to evidence-based practice, incorporation of information and communication technologies in health and information management. PMID- 27007429 TI - [Time standards of nursing in Primary Health Care: an observational study]. AB - OBJECTIVE: To determine time standards for interventions and activities conducted by nursing professionals in Family Health Units (FHU) in Brazil to substantiate the calculation of work force. METHOD: This was an observational study carried out in 27 FHU, in 12 municipalities in 10 states, in 2013. In each unit, nursing professionals were observed every 10 minutes, for eight work hours, on five consecutive days via the work sampling technique. RESULTS: A total of 32,613 observations were made, involving 47 nurses and 93 nursing technicians/assistants. Appointments were the main intervention carried out by nurses, with a mean time of 25.3 minutes, followed by record-keeping, which corresponded to 9.7%. On average, nursing technicians/assistants spent 6.3% of their time keeping records and 30.6 intervention minutes on immunization/vaccination control. CONCLUSION: The study resulted in standard times of interventions carried out by the FHU nursing team, which can underpin the determination of nursing staff size and human resource policies. Furthermore, the study showed the panorama of interventions currently employed, allowing for the work process to be reviewed and optimized. PMID- 27007430 TI - [Aromatherapy and nursing: historical and theoretical conception]. AB - Aromatherapy is a Practical or Complementary Health Therapy that uses volatile concentrates extracted from plants called essential oils, in order to improve physical, mental and emotional well-being. Aromatherapy has been practiced historically and worldwide by nurses and, as in Brazil is supported by the Federal Nursing Council, it is relevant to discuss this practice in the context of Nursing through Theories of Nursing. This study of theoretical reflection, exploratory and descriptive, aims to discuss the pharmacognosy of essential oils, the historical trajectory of Aromatherapy in Nursing and the conceptions to support Aromatherapy in light of eight Nursing Theorists (Florence Nightingale, Myra Levine, Hildegard Peplau, Martha Rogers, Callista Roy, Wanda Horta, Jean Watson and Katharine Kolcaba), contributing to its inclusion as a nursing care practice. PMID- 27007431 TI - [Preventing violence by intimate partners in adolescence: an integrative review]. AB - OBJECTIVE: To analyze the scientific literature on preventing intimate partner violence among adolescents in the field of health based on gender and generational categories. METHOD: This was an integrative review. We searched for articles using LILACS, PubMed/MEDLINE, and SciELO databases. RESULTS: Thirty articles were selected. The results indicate that most studies assessed interventions conducted by programs for intimate partner violence prevention. These studies adopted quantitative methods, and most were in the area of nursing, psychology, and medicine. Furthermore, most research contexts involved schools, followed by households, a hospital, a health center, and an indigenous tribe. CONCLUSION: The analyses were not conducted from a gender- and generation-based perspective. Instead, the scientific literature was based on positivist research models, intimately connected to the classic public healthcare model and centered on a singular dimension. PMID- 27007432 TI - [Composition of the electrocautery smoke: integrative literature review]. AB - OBJECTIVE: To identify the composition of the smoke produced by electrocautery use during surgery. METHOD: Integrative review with search for primary studies conducted in the databases of the US National Library of Medicine National Institutes of Health, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences, covering the studies published between 2004 and 2014. RESULTS: The final sample consisted of 14 studies grouped into three categories, namely; polycyclic aromatic hydrocarbons, volatile compounds and volatile organic compounds. CONCLUSION: There is scientific evidence that electrocautery smoke has volatile toxic, carcinogenic and mutagenic compounds, and its inhalation constitutes a potential chemical risk to the health of workers involved in surgeries. PMID- 27007433 TI - [Nursing care in the anesthetic procedure: an integrative review]. AB - OBJECTIVE: To search for the scientific evidence available on nursing professional actions during the anesthetic procedure. METHOD: An integrative review of articles in Portuguese, English and Spanish, indexed in MEDLINE/PubMed, CINAHL, LILACS, National Cochrane, SciELO databases and the VHL portal. RESULTS: Seven studies were analyzed, showing nurse anesthetists' work in countries such as the United States and parts of Europe, with the formulation of a plan for anesthesia and patient care regarding the verification of materials and intraoperative controls. The barriers to their performance involved working in conjunction with or supervised by anesthesiologists, the lack of government guidelines and policies for the legal exercise of the profession, and the conflict between nursing and the health system for maintenance of the performance in places with legislation and defined protocols for the specialty. CONCLUSION: Despite the methodological weaknesses found, the studies indicated a wide diversity of nursing work. Furthermore, in countries absent of the specialty, like Brazil, the need to develop guidelines for care during the anesthetic procedure was observed. PMID- 27007434 TI - [An integrative review of drug utilization by the elderly in primary health care]. AB - OBJECTIVE: To identify knowledge produced about drug utilization by the elderly in the primary health care context from 2006 to 2014. METHOD: An integrative review of the PubMed, LILACS, BDENF, and SCOPUS databases, including qualitative research papers in Portuguese, English, and Spanish. It excluded papers with insufficient information regarding the methodological description. RESULTS: Search found 633 papers that, after being subjected to the inclusion and exclusion criteria, made up a corpusof 76 publications, mostly in English and produced in the United States, England, and Brazil. Results were pooled in eight thematic categories showing the current trend of drug use in the elderly, notably the use of psychotropics, polypharmacy, the prevention of adverse events, and adoption of technologies to facilitate drug management by the elderly. Studies point out the risks posed to the elderly as a consequence of changes in metabolism and simultaneous use of several drugs. CONCLUSION: There is strong concern about improving communications between professionals and the elderly in order to promote an exchange of information about therapy, and in this way prevent major health complications in this population. PMID- 27007435 TI - Current Practice in the Referral of Individuals with Suspected Dementia for Neuroimaging by General Practitioners in Ireland and Wales. AB - OBJECTIVES: While early diagnosis of dementia is important, the question arises whether general practitioners (GPs) should engage in direct referrals. The current study investigated current referral practices for neuroimaging in dementia, access to imaging modalities and investigated related GP training in Ireland and North Wales. METHODS: A questionnaire was distributed to GPs in the programme regions which included approximately two thirds of all GPs in the Republic of Ireland and all general practitioners in North Wales. A total of 2,093 questionnaires were issued. RESULTS: 48.6% of Irish respondents and 24.3% of Welsh respondents directly referred patients with suspected dementia for neuroimaging. Irish GPs reported greater direct access to neuroimaging than their Welsh counterparts. A very small percentage of Irish and Welsh GPs (4.7% and 10% respectively) had received training in neuroimaging and the majority who referred patients for neuroimaging were not aware of any dementia-specific protocols for referrals (93.1% and 95% respectively). CONCLUSIONS: The benefits of direct GP access to neuroimaging investigations for dementia have yet to be established. Our findings suggest that current GP speciality training in Ireland and Wales is deficient in dementia-specific and neuroimaging training with the concern being that inadequate training will lead to inadequate referrals. Further training would complement guidelines and provide a greater understanding of the role and appropriateness of neuroimaging techniques in the diagnosis of dementia. PMID- 27007436 TI - Injectable hydrogels embedded with alginate microspheres for controlled delivery of bone morphogenetic protein-2. AB - Some delivery carriers with injectable characteristics were built using the thermosensitive chitosan/dextran-polylactide/glycerophosphate hydrogel and selected alginate microspheres for the controllable release of bone morphogenetic protein-2 (BMP-2). BMP-2 was first loaded into the microspheres with an average size of around 20 MUm and the resulting microspheres were then embedded into the gel in order to achieve well-controlled BMP-2 release. The microsphere-embedded gels show their incipient gelation temperature at around 32 degrees C and pH at about 7.1. Some gels had their elastic modulus close to 1400 Pa and the ratio of elastic modulus to viscous modulus at around 34, revealing that they behaved like mechanically strong gels. Optimized microsphere-embedded gels were found to be able to administer the BMP-2 release without significant initial burst release in an approximately linear manner over a period of time longer than four weeks. The release rate and the released amount of BMP-2 from these gels could be regulated individually or cooperatively by the initial BMP-2 load and the dextran polylactide content in the gels. Measurements of the BMP-2 induced alkaline phosphatase activity in C2C12 cells confirmed that C2C12 cells responded to BMP-2 in a dose-dependent way and the released BMP-2 from the microsphere-embedded gels well retained their bioactivity. In vivo assessment of some gels revealed that the released BMP-2 maintained its osteogenesis functions. PMID- 27007442 TI - An Elephant-But Not Just in the Emergency Room. PMID- 27007437 TI - Complement Factor H-Related Protein 3 Serum Levels Are Low Compared to Factor H and Mainly Determined by Gene Copy Number Variation in CFHR3. AB - The major human complement regulator in blood, complement factor H (FH), has several closely related proteins, called FH-related (FHR) proteins. As all FHRs lack relevant complement regulatory activity, their physiological role is not well understood. FHR protein 3 (FHR-3) has been suggested to compete with FH for binding to Neisseria meningitidis, thereby affecting complement-mediated clearance. Clearly, the in vivo outcome of such competition greatly depends on the FH and FHR-3 concentrations. While FH levels have been established, accurate FHR-3 levels were never unequivocally reported to date. Moreover, CFHR3 gene copy numbers commonly vary, which may impact the FHR-3 concentration. Hence, we generated five anti-FHR-3 mAbs to specifically measure FHR-3 in human healthy donors of which we determined the gene copy number variation at the CFH/CFHR locus. Finally, we examined the acute-phase response characteristics of FHR-3 in a small sepsis cohort. We determined FHR-3 levels to have a mean of 19 nM and that under normal conditions the copy number of CFHR3 correlates to a very large extent with the FHR-3 serum levels. On average, FHR-3 was 132-fold lower compared to the FH concentration in the same serum samples and FHR-3 did not behave as a major acute phase response protein. PMID- 27007443 TI - An Initial Look at the Associations of a Variety of Health-Related Online Activities With Cancer Fatalism. AB - It has been an important public health goal to remove cancer fatalism because of its negative influence on both cancer screening and preventive behaviors. The present study examines roles of the Internet, as an emerging, crucial source of cancer information, in the effect of education on cancer fatalism. Based on our secondary analysis of a nationally representative survey (i.e., Health Information National Trends Survey 4 Cycle 1), we found that people with low levels of education are less likely than their more educated counterparts to engage in online health information seeking that is negatively linked to fatalistic beliefs about cancer prevention. In addition, the effect of education on online health information seeking was detected only among people who trust online health information. The implications of these findings for cancer control and for research on the digital divide and communication inequalities are discussed. PMID- 27007445 TI - Excited-State Absorption from Real-Time Time-Dependent Density Functional Theory: Optical Limiting in Zinc Phthalocyanine. AB - Optical-limiting materials are capable of attenuating light to protect delicate equipment from high-intensity light sources. Phthalocyanines have attracted a lot of attention for optical-limiting applications due to their versatility and large nonlinear absorption. With excited-state absorption (ESA) being the primary mechanism for optical limiting behavior in phthalocyanines, the ability to tune the optical absorption of ground and excited states in phthalocyanines would allow for the development of advanced optical limiters. We recently developed a method for the calculation of ESA based on real-time time-dependent density functional theory propagation of an excited-state density. In this work, we apply the approach to zinc phthalocyanine, demonstrating the ability of our method to efficiently identify the optical limiting potential of a molecular complex. PMID- 27007444 TI - New tools for experimental diabetes research: Cellular reprogramming and genome editing. AB - Isolated human islets are a rare and precious material for diabetes research. However, their availability is limited, and it is impossible to obtain them from patients with specific genotypes. Human pluripotent stem cells provide an alternative. Induced pluripotent stem cells can be generated from any individual's somatic cells and differentiated into pancreatic cells. Currently, this approach is limited by the immaturity of the islet-like cells derived from stem cells. However, this approach can already be used to model developmental defects, and the possibilities for studying insulin secretion are continuously improving. In addition, genome editing using the CRISPR/Cas9 technology provides powerful possibilities to study the impact of specific genotypes. The same technology can also be used for transcriptional regulation in order to improve the functional maturation of stem cell-derived islets. These tools are today becoming available for tomorrow's translational diabetes research. PMID- 27007446 TI - Irisin Is Regulated by CAR in Liver and Is a Mediator of Hepatic Glucose and Lipid Metabolism. AB - Irisin, a hormone proteolytically processed from fibronectin type III domain containing protein 5 (FNDC5), has been reported to induce the browning of sc adipocytes by increasing the level of uncoupling protein 1. In this study, we showed that activation of the nuclear receptor constitutive androstane receptor induced FNDC5 mRNA expression in the liver and increased the circulating level of irisin in mice. FNDC5/irisin is a direct transcriptional target of constitutive androstane receptor. Hepatic-released irisin functioned as a paracrine/autocrine factor that inhibited lipogenesis and gluconeogenesis via the Adenosine 5' monophosphate (AMP)-activated protein kinase pathway. Adenovirus-overexpressed irisin improved hepatic steatosis and insulin resistance in genetic-induced obese mice. Irisin transgenic mice were also protected against high-fat diet-induced obesity and insulin resistance. In conclusion, our results reveal a novel pathway in regulating FNDC5/irisin expression and identify a physiological role for this hepatic hormone in glucose and lipid homeostasis. PMID- 27007447 TI - Hypersexuality in Psychiatric Conditions Observer-Rated Scale (HIPCORS): Evaluation of Reliability and Validity. AB - Hypersexual behavior is not uncommon in psychiatric presentations. Most available scales that measure hypersexual behavior are self-rated, often containing sexually explicit questions, unsuitable for use in mentally unwell people. Lack of a clinically suitable instrument may have resulted in underdetection and under researching of hypersexuality in people with mental disorders, with potential to cause significant consequences for themselves and those around them, including family members, coclients, and clinicians. To address this need, we developed the Hypersexuality in Psychiatric Conditions Observer-Rated Scale (HIPCORS), a rater rated, nonintrusive tool, designed for use in mentally unwell people. It has been shown to be a reliable and valid instrument. PMID- 27007448 TI - Highly Fluorescent dye-nanoclay Hybrid Materials Made from Different Dye Classes. AB - Nanoclays like laponites, which are commercially avaible in large quantities for a very moderate price, provide a facile solubilization strategy for hydrophobic dyes without the need for chemical functionalization and can act as a carrier for a high number of dye molecules. This does not require reactive dyes, amplifies fluorescence signals from individual emitters due to the high number of dyes molecules per laponite disk, and renders hydrophobic emitters applicable in aqueous environments. Aiming at the rational design of bright dye-loaded nanoclays as a new class of fluorescent reporters for bioanalysis and material sciences and the identification of dye structure-property relationships, we screened a series of commercial fluorescent dyes, differing in dye class, charge, and character of the optical transitions involved, and studied the changes of their optical properties caused by clay adsorption at different dye loading concentrations. Upon the basis of our dye loading density-dependent absorption and fluorescence measurements with S2105 and Lumogen F Yellow 083, we could identify two promising dye-nanoclay hybrid materials that reveal high fluorescence quantum yields of the nanoclay-adsorbed dyes of at least 0.20 and low dye self-quenching even at high dye-loading densities of up to 50 dye molecules per laponite platelet. PMID- 27007450 TI - From the Editor-in-Chief's Desk. PMID- 27007451 TI - Disruptive Mood Dysregulation Disorder: Where Did It Come from and Where Is It Going. PMID- 27007449 TI - Glioblastoma Induces Vascular Dysregulation in Nonenhancing Peritumoral Regions in Humans. AB - OBJECTIVE: Glioblastoma is an invasive primary brain malignancy that typically infiltrates the surrounding tissue with malignant cells. It disrupts cerebral blood flow through a variety of biomechanical and biochemical mechanisms. Thus, neuroimaging focused on identifying regions of vascular dysregulation may reveal a marker of tumor spread. The purpose of this study was to use blood oxygenation level-dependent (BOLD) functional MRI (fMRI) to compare the temporal dynamics of the enhancing portion of a tumor with those of brain regions without apparent tumors. MATERIALS AND METHODS: Patients with pathologically proven glioblastoma underwent preoperative resting-state BOLD fMRI, T1-weighted contrast-enhanced MRI, and FLAIR MRI. The contralesional control hemisphere, contrast-enhancing tumor, and peritu-moral edema were segmented by use of structural images and were used to extract the time series of these respective regions. The parameter estimates (beta values) for the two regressors and resulting z-statistic images were used as a metric to compare the similarity of the tumor dynamics to those of other brain regions. RESULTS: The time course of the contrast-enhancing tumor was significantly different from that of the rest of the brain (p < 0.05). Similarly, the control signal intensity was significantly different from the tumor signal intensity (p < 0.05). Notably, the temporal dynamics in the peritumoral edema, which did not contain enhancing tumor, were most similar to the those of enhancing tumor than to those of control regions. CONCLUSION: The findings show that the disruption in vascular regulation induced by a glioblastoma can be detected with BOLD fMRI and that the spatial distribution of these disruptions is localized to the immediate vicinity of the tumor and peritumoral edema. PMID- 27007452 TI - Quetiapine Addiction in an Adolescent. PMID- 27007453 TI - How should we monitor boys with testicular microlithiasis? AB - Testicular microlithiasis (TM), a rare condition characterized by calcification within the seminiferous tubules, is associated with benign and malignant disorders of the testis. We review current practices of following up pediatric patients diagnosed TM incidentally on scrotal ultrasonography (US). We analyzed retrospectively patient characteristics, family history, indications for US, pathological features, US findings, outcome, and follow-up. At our institution, 2875 scrotal US examinations were performed on 2477 children with various scrotal complaints from 2008 to 2015. Testicular microlithiasis was detected in 81 patients (i.e., an incidence of 3.27%). Every 6 months, each patient underwent a clinical and ultrasonographic evaluation as well as serum tumor markers determination to detect a potential malignancy. Seventy-eight patients who had undergone scrotal US at least twice were included in this study. We evaluated the US studies for the type of TM (diffuse and focal) and change in follow-up studies. Testicular microlithiasis was typically diffuse (n = 56, 71.8%) and bilateral (n = 45, 57.7%), and it was detected the most frequently in the 9-11 year age group (27 patients, 34.6%). The most common comorbid conditions included undescended testes (31 patients, 39.7%) and hydrocele (11 patients, 14.1%). We found that serum tumor markers were within normal limits both at diagnosis and upon follow-up. No testicular tumors or new abnormal symptoms developed during the clinical follow-up. There is no convincing evidence that TM alone is premalignant in a pediatric population. In terms of follow-up, we advise regular self-examinations and annual US in the absence of risk factors. PMID- 27007454 TI - Benzylic C-H Azidation Using the Zhdankin Reagent and a Copper Photoredox Catalyst. AB - An azidation method for C-N bond formation at benzylic C-H positions is described using copper-catalyzed visible light photochemistry and the Zhdankin azidoiodinane reagent. The method is applicable to a wide range of substrates bearing different functional groups and having a primary, secondary, or tertiary benzylic position, and is thought to proceed through a radical chain reaction. PMID- 27007455 TI - Biaxial Dielectrophoresis Force Spectroscopy: A Stoichiometric Approach for Examining Intermolecular Weak Binding Interactions. AB - The direct quantification of weak intermolecular binding interactions is very important for many applications in biology and medicine. Techniques that can be used to investigate such interactions under a controlled environment, while varying different parameters such as loading rate, pulling direction, rupture event measurements, and the use of different functionalized probes, are still lacking. Herein, we demonstrate a biaxial dielectrophoresis force spectroscopy (BDFS) method that can be used to investigate weak unbinding events in a high throughput manner under controlled environments and by varying the pulling direction (i.e., transverse and/or vertical axes) as well as the loading rate. With the BDFS system, we can quantitatively analyze binding interactions related to hydrogen bonding or ionic attractions between functionalized microbeads and a surface within a microfluidic device. Our BDFS system allowed for the characterization of the number of bonds involved in an interaction, bond affinity, kinetic rates, and energy barrier heights and widths from different regimes of the energy landscape. PMID- 27007456 TI - Laparoscopic Nissen Fundoplication: Analysis of 162 patients. AB - METHODS: One hundred and sixty-two patients with GERD were treated surgically with LNF from October 2006 to March 2010. Diagnoses were made by using upper gastrointestinal system (GIS) endoscopy and 24-hour pH monitoring, and all the patients underwent routine LNF surgery. The patients were questioned regarding complaints and proton pump inhibitor (PPI) usage during the postoperative period, and forty patients who had postoperative GIS symptoms were included. Upper GIS endoscopy with antral biopsy for Helicobacter pylori (HP) identification and multichannel intraluminal impedance pH(MII-pH) monitoring were applied Results:The median postoperative follow-up time was 1.84 A+/- 0.850 (0.29-3.48) years. PPI treatment frequency was 37.5% (15 patients) in the 40 symptomatic 40 patients, or 9.26% in all 162 patients who were operated on. The reason for PPI usage in three patients (7.5%) was regarded as recurrence. HP positivity was 67.5% in the symptomatic patients and 73.3% in the PPI treated group; 40% (six patients) recovery was achieved in the HP (+) patients by using an HP eradication treatment protocol. The operated patients displayed statistically significant results in increased quality of life (p = 0.001) and lowered DeMeester scores (p = 0.000) during the postoperative period when compared to preoperative period. CONCLUSION: PPI treatment alone during the postoperative period does not indicate recurrence. One of the most important reasons for recurrence is antral gastritis secondary to HP infection; PPI usage diminishes remarkably with an HP eradication protocol. MII-pH monitoring is an effective method of determining recurrences due to reflux and their types in postoperative symptomatic patients. PMID- 27007462 TI - MDCT in ischaemic colitis: how to define the aetiology and acute, subacute and chronic phase of damage in the emergency setting. AB - Ischemic colitis (IC) is the most common vascular disorder of the gastrointestinal tract with a reported incidence of 6.1-44 cases/100,000 person years with confirmatory histopathology. However, the true incidence of IC poses some difficulty, and even vigilant clinicians with patients at high risk often miss the diagnosis, since clinical presentation is non-specific or could have a mild transient nature. Detection of IC results is crucial to plan the correct therapeutic approach and reduce the reported mortality rate (4-12%). Diagnosis of IC is based on a combination of clinical suspicion, radiological, endoscopic and histological findings. Some consider colonoscopy as a diagnostic test of choice; however, preparation is required and it is not without risk, above all in patients who are severely ill. There are two manifestations of vascular colonic insult: ischaemic and reperfusive. The first one occurs above all during ischaemic/non-occlusive mesenteric ischaemia; in this case, the colonic wall appears thinned with dilated lumen and fluid appears in the paracolic space. When reperfusion occurs, the large bowel wall appears thickened and stratified, because of subepithelial oedema and/or haemorrhage, with consequent lumen calibre reduction. Shaggy contour of the involved intestine and misty mesentery are associated with the pericolic fluid. The pericolic fluid results are a crucial finding for IC diagnosis since its evidence suggests the presence of an ongoing damage thus focusing the attention on other pathological aspects which could be otherwise misdiagnosed, such as thinned or thickened colonic wall. Moreover, the pericolic fluid may increase or decrease, depending on the evolution of the ischaemic damage, suggesting the decision of medical or surgical treatment. Radiologists should not forget the hypothesis of IC, being aware that multidetector CT could be sufficient to suggest the diagnosis of IC, allowing for early identification and grading definition, and in a short-term follow-up, discriminating patients who need urgent surgery from patients in whom medical treatment and follow-up can be proposed. PMID- 27007464 TI - Nodal expression in triple-negative breast cancer: Cellular effects of its inhibition following doxorubicin treatment. AB - Triple-negative breast cancer (TNBC) represents an aggressive cancer subtype characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The independence of TNBC from these growth promoting factors eliminates the efficacy of therapies which specifically target them, and limits TNBC patients to traditional systemic neo/adjuvant chemotherapy. To better understand the growth advantage of TNBC - in the absence of ER, PR and HER2, we focused on the embryonic morphogen Nodal (associated with the cancer stem cell phenotype), which is re-expressed in aggressive breast cancers. Most notably, our previous data demonstrated that inhibition of Nodal signaling in breast cancer cells reduces their tumorigenic capacity. Furthermore, inhibiting Nodal in other cancers has resulted in improved effects of chemotherapy, although the mechanisms for this remain unknown. Thus, we hypothesized that targeting Nodal in TNBC cells in combination with conventional chemotherapy may improve efficacy and represent a potential new strategy. Our preliminary data demonstrate that Nodal is highly expressed in TNBC when compared to invasive hormone receptor positive samples. Treatment of Nodal expressing TNBC cell lines with a neutralizing anti-Nodal antibody reduces the viability of cells that had previously survived treatment with the anthracycline doxorubicin. We show that inhibiting Nodal may alter response mechanisms employed by cancer cells undergoing DNA damage. These data suggest that development of therapies which target Nodal in TNBC may lead to additional treatment options in conjunction with chemotherapy regimens - by altering signaling pathways critical to cellular survival. PMID- 27007465 TI - Inhibitory Effects of AVEMAR on Proliferation and Metastasis of Oral Cancer Cells. AB - Oral cancer is keeping its 4th rank on the death causing cancers among Taiwan males, and its metastatic and recurrent rates remain high and a life-threatening issue to the citizens. Fermented wheat germ extract (AVEMAR) is used in clinical cancer nutritional therapy in gastrointestinal cancers but not in oral cancer yet. In this study, the potential of AVEMAR to inhibit tumor proliferation and metastasis of oral cancer was first investigated. Antiproliferative activity of AVEMAR was determined in human oral squamous carcinoma SCC-4 cells by MTT methodology. Wound-healing migration, transwell invasion, and Western blotting assays were carried out to examine the in vitro antimetastatic effects and involved signaling molecules for AVEMAR in oral cancer cells. AVEMAR at 0.2-1.6 mg/ml significantly inhibited the cell viability with IC50 values of 1.19 and 0.98 mg/ml for 24-h and 48-h treatment. Furthermore, AVEMAR could induce cell apoptosis and inhibit the migration and invasion of metastatic SCC-4 cells at a similar dose range. Notably, AVEMAR suppressed the expression of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (u-PA), but not MMP 1 or MMP-9, in SCC-4 cells. These results strongly support the antiproliferation and in vitro antimetastatic capacity of AVEMAR which may extend its contributions from cancer nutrition supplements to preventive agent for oral cancer. PMID- 27007467 TI - Bladder paraganglioma: safe and feasible management with robot assisted surgery. AB - Pheochromocytomas of extra-adrenal origin are known as paragangliomas. Urinary bladder is the most common site of genitourinary paragangliomas. The variable functional status of these tumors presents a surgical challenge in their management by minimally invasive surgery. Robot-assisted partial cystectomy offers the advantage of minimal handling of tumor, early ligation of feeding vessels and easy suturing. We hereby report the feasibility and safety of robot assisted surgery in the management of one such case. PMID- 27007468 TI - Principles of a risk evaluation and mitigation strategy (REMS) for breast cancer patients receiving potentially cardiotoxic adjuvant treatments. AB - INTRODUCTION: The number of breast cancer long survivors has increased in the last few years. However, this increase in survival may be affected by the side effects of adjuvant breast cancer therapies. In this context cardiovascular toxicity is considered one of the most clinically important toxicities. AREAS COVERED: In this work we review the published clinical trials of adjuvant treatment on breast cancer, focusing on the trials which accurately mentioned the cardiotoxicity of the adjuvant treatments and those which underwent long term follow up of cardiac function. This article tries to summarize and evaluate the risk of cardiac toxicities associated with different adjuvant treatments for breast cancer (chemotherapy, radiotherapy, endocrine therapy and trastuzumab). EXPERT OPINION: In our opinion, each individual breast cancer patient should be meticulously evaluated before starting adjuvant treatment in order to basically asses cardiac function and to manage any predisposing risk factor which may increase the probability of treatment induced cardiotoxicity. Rigorous and frequent reassessment of cardiac function along with providing different mitigation strategies that can prevent or decrease the risk of such cardiovascular toxicities are inevitable methods to protect the patient from cardiac events which can mask the survival benefit associated with different adjuvant treatments. PMID- 27007463 TI - Exposure-based Interventions for the management of individuals with high levels of needle fear across the lifespan: a clinical practice guideline and call for further research. AB - Needle fear typically begins in childhood and represents an important health related issue across the lifespan. Individuals who are highly fearful of needles frequently avoid health care. Although guidance exists for managing needle pain and fear during procedures, the most highly fearful may refuse or abstain from such procedures. The purpose of a clinical practice guideline (CPG) is to provide actionable instruction on the management of a particular health concern; this guidance emerges from a systematic process. Using evidence from a rigorous systematic review interpreted by an expert panel, this CPG provides recommendations on exposure-based interventions for high levels of needle fear in children and adults. The AGREE-II, GRADE, and Cochrane methodologies were used. Exposure-based interventions were included. The included evidence was very low quality on average. Strong recommendations include the following. In vivo (live/in person) exposure-based therapy is recommended (vs. no treatment) for children seven years and older and adults with high levels of needle fear. Non-in vivo (imaginal, computer-based) exposure (vs. no treatment) is recommended for individuals (over seven years of age) who are unwilling to undergo in vivo exposure. Although there were no included trials which examined children < 7 years, exposure-based interventions are discussed as good clinical practice. Implementation considerations are discussed and clinical tools are provided. Utilization of these recommended practices may lead to improved health outcomes due to better health care compliance. Research on the understanding and treatment of high levels of needle fear is urgently needed; specific recommendations are provided. PMID- 27007469 TI - The Internalized Homophobia Scale for Vietnamese Sexual Minority Women: Conceptualization, Factor Structure, Reliability, and Associations With Hypothesized Correlates. AB - We developed the first Vietnamese Internalized Homophobia (IH) scale for use with Vietnamese sexual minority women (SMW). Drawing from existing IH scales in the international literature and based on prior qualitative research about SMW in the Viet Nam context, the scale covers two domains: self-stigma (negative attitudes toward oneself as a sexual minority person) and sexual prejudice (negative attitudes toward homosexuality/same-sex relations in general). Scale items, including items borrowed from existing scales and items based on local expressions, were reviewed and confirmed by members of the target population. Quantitative evaluation used data from an anonymous web-based survey of Vietnamese SMW, including those who identified as lesbian (n = 1187), or as bisexual (n = 641) and those who were unsure about their sexual identity (n = 353). The scale was found to consist of two highly correlated factors reflecting self-stigma (not normal/wholesome and self-reproach and wishing away same-sex sexuality) and one factor reflecting sexual prejudice, and to have excellent internal consistency. Construct validity was evidenced by subscale associations with a wide range of hypothesized correlates, including perceived sexual stigma, outness, social support, connection to other SMW, relationship quality, psychological well-being, anticipation of heterosexual marriage, and endorsement of same-sex marriage legalization. Self-stigma was more strongly associated with psychosocial correlates, and sexual prejudice was more associated with endorsement of legal same-sex marriage. The variations in these associations across the hypothesized correlates and across sexual identity groups were consistent with the minority stress model and the IH literature, and exhibited context-specific features, which are discussed. PMID- 27007470 TI - "We Might Get Some Free Beers": Experience and Motivation for Transactional Sex Among Behaviorally Bisexual Men in Vientiane, Laos. AB - People engaging in transactional sex are considered a key population for HIV prevention. Prior quantitative surveys demonstrated that behaviorally bisexual men in Vientiane, Laos commonly transact sex. In 2013, we conducted a qualitative study to explore behaviorally bisexual men's experience, motivations, and perceptions related to transactional sex in Vientiane. Behaviorally bisexual men were recruited from bars, nightclubs, and dormitories for five focus group discussions (FGDs) and 11 in-depth interviews (n = 31). Additionally, young women were recruited from a university, garment factory, and nightclub for four FGDs (n = 22). Transcripts were translated and thematically coded. Bisexual male participants most commonly described being paid for sex by male-to-female transgender people and buying sex from women. Both male and female participants reported that older, single women pay younger men for sex. Negotiation and direction of sexual transactions are influenced by age, attraction, and wealth. Common motivations for selling sex included the need for money to support family or fund school fees, material gain, or physical pleasure. Transactional sex was often opportunistic. Some behaviorally bisexual men reported selling sex in order to pay another more desirable sex partner or to buy gifts for their regular sex partner. Participants perceived high risk associated with intercourse with female sex workers but not with other transactional sex partners. Health interventions are needed to improve knowledge, risk perception, and health behaviors, but must recognize the diversity of transactional sex in Vientiane. Both physical and virtual settings may be appropriate for reaching behaviorally bisexual men and their partners. PMID- 27007471 TI - Defining Pleasure: A Focus Group Study of Solitary and Partnered Sexual Pleasure in Queer and Heterosexual Women. AB - Solitary and partnered sexuality are typically depicted as fundamentally similar, but empirical evidence suggests they differ in important ways. We investigated how women's definitions of sexual pleasure overlapped and diverged when considering solitary versus partnered sexuality. Based on an interdisciplinary literature, we explored whether solitary pleasure would be characterized by eroticism (e.g., genital pleasure, orgasm) and partnered pleasure by nurturance (e.g., closeness). Via focus groups with a sexually diverse sample of women aged 18-64 (N = 73), we found that women defined solitary and partnered pleasure in both convergent and divergent ways that supported expectations. Autonomy was central to definitions of solitary pleasure, whereas trust, giving pleasure, and closeness were important elements of partnered pleasure. Both solitary and partnered pleasure involved exploration for self-discovery or for growing a partnered relationship. Definitions of pleasure were largely similar across age and sexual identity; however, relative to queer women, heterosexual women (especially younger heterosexual women) expressed greater ambivalence toward solitary masturbation and partnered orgasm. Results have implications for women's sexual well-being across multiple sexual identities and ages, and for understanding solitary and partnered sexuality as overlapping but distinct constructs. PMID- 27007472 TI - Is Semantics Affected by Missing a Critical Period? Evidence from the Persian Deaf. AB - The present study aims to explore the semantic knowledge of a group of Iranian deaf individuals who, due mainly to auditory deprivation did not acquire language normally in early years of their life. The participants were ten deaf and a matched number of hearing individuals as control group. A test of five tasks was administrated to assess their knowledge of vocabulary, collocation, semantic categorizations, semantic features, and proverbs. Although the results indicated a significant difference between the deaf and the hearing group, a between- group comparison of each task revealed no significant difference between the deaf and hearing participants in the number of errors in vocabulary, collocations, semantic categorization, and semantic features. The only task in which deaf participants did significantly worse than the control group was that of proverbs. Therefore, it could be argued that, language deprivation in early childhood does not have the same effect on different components of our linguistic knowledge and that the acquisition of semantics may well continue beyond puberty. PMID- 27007473 TI - Electromagnetic tracking of the pivot-shift. AB - The pivot-shift test is an important examination to assess the rotational laxity in the anterior cruciate ligament (ACL) injured and reconstructed knees. Because this examination is related to subjective knee function, we may still see cases that have residual rotational laxity after ACL reconstruction. Quantitative evaluation of the pivot-shift test is preferable to the clinical pivot-shift test but is difficult to attain mainly due to complicated movements of the pivot shift. The electromagnetic tracking system was developed to evaluate knee kinematics during the pivot-shift, providing information related to 6-degree-of freedom knee kinematics with a high sampling rate. Through this device, the abnormal movement of the pivot-shift is characterized in two phases: an increased anterior tibial translation and a boosted acceleration of tibial posterior reduction. Since its invention, this system has been utilized to assess rotational laxity for clinical follow-up and research after the ACL reconstruction. PMID- 27007475 TI - Has sclerostin a true endocrine metabolic action complementary to osteocalcin in older men? AB - The reported association between sclerostin and diabetes mellitus or abdominal fat may be biased by body size and bone mass. In older men, the association between serum sclerostin levels and metabolic syndrome lost significance after adjustment for bone mass. The association between sclerostin and energy metabolism needs further clarification. INTRODUCTION: Sclerostin is associated with abdominal fat, but this relationship may be biased since both are associated with body size and bone mass. Osteocalcin is a bone-derived hormone regulating energy metabolism. We assessed the association between serum sclerostin and metabolic syndrome (MetS) accounting for whole body mineral content (BMC) and osteocalcin. METHODS: We studied 694 men aged 51-85 who had serum osteocalcin and sclerostin measurements. RESULTS: Sclerostin was higher in 216 men with MetS compared with those without MetS (p < 0.005). Average sclerostin level increased significantly across the increasing number of MetS components. In multivariable models, higher sclerostin was associated with higher odds of MetS (odds ratio (OR) = 1.24/1 standard deviation (SD) increase [95 % confidence interval (95 % CI), 1.01-1.51]; p < 0.05). After further adjustment for BMC, the association of MetS with sclerostin lost significance, whereas that with osteocalcin remained significant. Men who were simultaneously in the highest sclerostin quartile and the lowest osteocalcin quartile had higher odds of MetS (OR = 2.14 [95 % CI, 1.15 4.18]; p < 0.05) vs. men being in the three lower sclerostin quartiles and three upper osteocalcin quartiles. After adjustment for whole body BMC, the association lost significance. CONCLUSIONS: Higher sclerostin level is associated with MetS severity; however, this association may be related to higher whole body BMC. The adjustment for BMC had no impact on the association between MetS and osteocalcin. Clinical cross-sectional studies do not elucidate the potential role of sclerostin in the regulation of energy metabolism and direct experimental approach is necessary. PMID- 27007474 TI - Basic biomechanic principles of knee instability. AB - Motion at the knee joint is a complex mechanical phenomenon. Stability is provided by a combination of static and dynamic structures that work in concert to prevent excessive movement or instability that is inherent in various knee injuries. The anterior cruciate ligament (ACL) is a main stabilizer of the knee, providing both translational and rotatory constraint. Despite the high volume of research directed at native ACL function, pathogenesis and surgical reconstruction of this structure, a gold standard for objective quantification of injury and subsequent repair, has not been demonstrated. Furthermore, recent studies have suggested that novel anatomic structures may play a significant role in knee stability. The use of biomechanical principles and testing techniques provides essential objective/quantitative information on the function of bone, ligaments, joint capsule, and other contributing soft tissues in response to various loading conditions. This review discusses the principles of biomechanics in relation to knee stability, with a focus on the objective quantification of knee stability, the individual contributions of specific knee structures to stability, and the most recent technological advances in the biomechanical evaluation of the knee joint. PMID- 27007476 TI - Concordance between timeline follow-back and single-question assessment of self reported smoking in a clinical trial. AB - BACKGROUND: Smoking cessation clinical trials assess tobacco abstinence using self-report and biomarkers. Optimum methods for each are unclear; a common question assesses smoking in the prior 7 days. In contrast, timeline follow-back (TLFB) is another technique often used to assess use of alcohol in treatment trials; it is used less frequently in studies of smoking cessation. The goal of this study was to assess concordance between the 7-day smoking question and a 7 day TLFB. METHODS: Secondary analysis of data from a randomized clinical trial of smoking cessation was conducted at a busy, urban hospital emergency department (ED) from October 2010 to December 2012. At 1, 3, and 12 months, subjects were contacted by phone to assess smoking status. Those reporting abstinence at 3 months were asked to return for an in-person measurement of exhaled carbon monoxide. For this analysis, smoking status at 1 month was compared for subjects in response to 2 questions asked concurrently, addressing 7-day point prevalence tobacco use and a 7-day TLFB. RESULTS: Of 780 subjects, 666 (85.4%) were available for 1-month follow-up. Of these, 99 (14.9%) reported no smoking in response to the 7-day question, and 96 (14.4%) reported no smoking in response to the 7-day TLFB. The overall proportionate agreement between the 2 methods was 98.6%, with a kappa of 0.95 (95% confidence interval [CI]: 0.91-0.98). CONCLUSIONS: A single question that assesses smoking at 7 days provides excellent concordance with the more detailed TLFB. The single question appears adequate to assess self-reported tobacco use in clinical trials of smoking cessation. PMID- 27007477 TI - Effect of the retinal size of a peripheral cue on attentional orienting in two- and three-dimensional worlds. AB - It has been documented that due to limited attentional resources, the size of the attentional focus is inversely correlated with processing efficiency. Moreover, by adopting a variety of two-dimensional size illusions induced by pictorial depth cues (e.g., the Ponzo illusion), previous studies have revealed that the perceived, rather than the retinal, size of an object determines its detection. It remains unclear, however, whether and how the retinal versus perceived size of a cue influences the process of attentional orienting to subsequent targets, and whether the corresponding influencing processes differ between two-dimensional (2 D) and three-dimensional (3-D) space. In the present study, we incorporated the dot probe paradigm with either a 2-D Ponzo illusion, induced by pictorial depth cues, or a virtual 3-D world in which the Ponzo illusion turned into visual reality. By varying the retinal size of the cue while keeping its perceived size constant (Exp. 1), we found that a cue with smaller retinal size significantly facilitated attentional orienting as compared to a cue with larger retinal size, and that the effects were comparable between 2-D and 3-D displays. Furthermore, when the pictorial background was removed and the cue display was positioned in either the farther or the closer depth plane (Exp. 2), or when both the depth and the background were removed (Exp. 3), the retinal size, rather than the depth, of the cue still affected attentional orienting. Taken together, our results suggest that the retinal size of a cue plays the crucial role in the visuospatial orienting of attention in both 2-D and 3-D. PMID- 27007478 TI - Relationship between Poling Characteristics and Phase Boundaries of Potassium Sodium Niobate Ceramics. AB - The controversy about the optimum poling conditions of (K,Na)NbO3 (KNN)-based lead-free ceramics was still unresolved and the relationships between poling characteristics and phase boundary types were rarely mentioned. Here, we tried to unveil the relationships between poling characteristics and phase boundary types of these ceramics. The optimum poling temperatures should be chosen near their corresponding phase transition temperatures. In addition, a large piezoelectricity can be attained in the ceramics with a multiphase coexistence under a lower poling electric field (=E(C)) is required to achieve the sufficient polarization in the ones with single O or T phase. More interestingly, it is the first time to report that the ceramics with different phase boundaries can be fully poled after the measurement of P-E loops, where the d33 values match those of the corresponding ones poled by the DC electric field. We believe that this modified poling process can benefit the improved piezoelectricity of KNN-based ceramics. PMID- 27007480 TI - Diurnal Variations of Air-Soil Exchange of Semivolatile Organic Compounds (PAHs, PCBs, OCPs, and PBDEs) in a Central European Receptor Area. AB - Concentrations of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) in air and soil, their fugacities, and the experimental soil-air partitioning coefficient (KSA) were determined at two background sites in the Gt. Hungarian Plain in August 2013. The concentrations of the semivolatile organic compounds (SOCs) in the soil were not correlated with the organic carbon content but with two indirect parameters of mineralization and aromaticity, suggesting that soil organic matter quality is an important parameter affecting the sorption of SOCs onto soils. Predictions based on the assumption that absorption is the dominant process were in good agreement with the measurements for PAHs, OCPs, and the low chlorinated PCBs. In general, soils were found to be a source of PAHs, high chlorinated PCBs, the majority of OCPs and PBDEs, and a sink for the low chlorinated PCBs and gamma-hexachlorocyclohexane. Diurnal variations in the direction of the soil-air exchange were found for two compounds (i.e., pentachlorobenzene and p,p'-dichlorodiphenyldichloroethane), with volatilization during the day and deposition in the night. The concentrations of most SOCs in the near-ground atmosphere were dominated by revolatilization from the soil. PMID- 27007481 TI - Detection of in Vitro Metabolite Formation of Leflunomide: A Fluorescence Dynamics and Electronic Structure Study. AB - The metabolic transformation of antirheumatic fluorescent drug leflunomide into its active metabolite teriflunomide through isoxazole ring opening has been monitored in vitro using steady state and time domain fluorescence spectroscopy and density functional theory. During metabolic reaction, absorption of leflunomide split into two bands resembling absorption spectra of teriflunomide. The fluorescence spectra reveal slow conversion of leflunomide to E and Z forms of teriflunomide in aqueous medium, which becomes faster at basic pH. The E form, which is more potent as a drug, becomes more stable with an increase in the basicity of the medium. Both molecules are associated with charge transfer due to twisting in the lowest singlet excited state. Excited state charge transfer followed by proton transfer was also observed in the Z form during the ring opening of leflunomide. Quantum yield and radiative decay rates have been observed to decrease for the metabolite because of an increase in nonradiative decay channels. PMID- 27007479 TI - The importance of controlling mRNA turnover during cell proliferation. AB - Microbial gene expression depends not only on specific regulatory mechanisms, but also on cellular growth because important global parameters, such as abundance of mRNAs and ribosomes, could be growth rate dependent. Understanding these global effects is necessary to quantitatively judge gene regulation. In the last few years, transcriptomic works in budding yeast have shown that a large fraction of its genes is coordinately regulated with growth rate. As mRNA levels depend simultaneously on synthesis and degradation rates, those studies were unable to discriminate the respective roles of both arms of the equilibrium process. We recently analyzed 80 different genomic experiments and found a positive and parallel correlation between both RNA polymerase II transcription and mRNA degradation with growth rates. Thus, the total mRNA concentration remains roughly constant. Some gene groups, however, regulate their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulate their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lower mRNA levels by reducing mRNA stability or the transcription rate, respectively. We critically review here these results and analyze them in relation to their possible extrapolation to other organisms and in relation to the new questions they open. PMID- 27007483 TI - Long-term outcomes of behavior problems after epilepsy surgery in childhood. AB - Although over 50 % of youth with intractable epilepsy present with behavioral problems, the long-term prognosis after resective epilepsy surgery in childhood is unclear. This study evaluated such outcomes in a cohort of surgical and nonsurgical patients. Participants were 108 patients (71 underwent surgery) with childhood-onset intractable epilepsy; their mean age at follow-up was 19.9 (standard deviation 4.3) years. The parent-rated Child or Adult Behavior Checklist (CBCL/ABCL) was used to document behavior prior to surgery and again 4 11 years later, and at comparable time points in the nonsurgical group. We focus primarily on externalizing and related symptomology in evaluating the CBCL/ABCL Externalizing Behavior summary scale and the Somatic Complaints, Thought Problems, Attention Problems, Aggressive Behavior, Intrusive, and Rule-breaking Behavior syndrome scales. Both groups improved in the Externalizing Behavior summary scale and in domains reflecting Somatic Complaints, Thought Problems, and Attention Problems from baseline to follow-up. Surgical and nonsurgical patients did not differ on any domain, whereas seizure-free patients had fewer symptoms in almost all behavioral domains, compared to patients with seizures. Regression analyses revealed that the most consistent predictor of improved behavior was greater behavior problems at baseline. Younger age at baseline was associated with improvements in Externalizing Behavior. The described long-term outcomes of behavior problems among patients with childhood-onset intractable epilepsy are encouraging, in that modest improvements were noted among all patient groups. Furthermore, seizure freedom, whether achieved through surgery or medication management, was associated with fewer behavioral problems in most domains. PMID- 27007482 TI - Clinical features and prognostic factors of spinal cord sarcoidosis: a multicenter observational study of 20 BIOPSY-PROVEN patients. AB - Sarcoidosis of the spinal cord is a rare disease. The aims of this study are to describe the features of spinal cord sarcoidosis (SCS) and identify prognostic markers. We analyzed 20 patients over a 20-year period in 8 French hospitals. There were 12 men (60 %), mostly Caucasian (75 %). The median ages at diagnosis of sarcoidosis and myelitis were 34.5 and 37 years, respectively. SCS revealed sarcoidosis in 12 patients (60 %). Eleven patients presented with motor deficit (55 %) and 9 had sphincter dysfunction (45 %). The median initial Edmus Grading Scale (EGS) score was 2.5. The cerebrospinal fluid (CSF) showed elevated protein level (median: 1.00 g/L, interquartile range (IQR) 0.72-1.97), low glucose level (median 2.84 mmol/L, IQR 1.42-3.45), and elevated white cell count (median 22/mm(3), IQR 6-45). The cervical and thoracic cords were most often affected (90 %). All patients received steroids and an immunosuppressive drug was added in 10 cases (50 %). After a mean follow-up of 52.1 months (range 8-43), 18 patients had partial response (90 %), 7 displayed functional impairment (35 %), and the median final EGS score was 1. Six patients experienced relapse (30 %). There was an association between the initial and the final EGS scores (p = 0.006). High CSF protein level showed a trend toward an association with relapse (p = 0.076). The spinal cord lesion was often the presenting feature of sarcoidosis. Most patients experienced clinical improvement with corticosteroids and/or immunosuppressive treatment. The long-term functional prognosis was correlated with the initial severity. PMID- 27007484 TI - Traumatic brain injury and age at onset of cognitive impairment in older adults. AB - There is a deficiency of knowledge regarding how traumatic brain injury (TBI) is associated with age at onset (AAO) of cognitive impairment in older adults. Participants with a TBI history were identified from the Alzheimer's disease neuroimaging initiative (ADNI 1/GO/2) medical history database. Using an analysis of covariance (ANCOVA) model, the AAO was compared between those with and without TBI, and potential confounding factors were controlled. The AAO was also compared between those with mild TBI (mTBI) and moderate or severe TBI (sTBI). Lastly, the effects of mTBI were analyzed on the AAO of participants with clinical diagnoses of either mild cognitive impairment (MCI) or Alzheimer's disease (AD). The AAO for a TBI group was 68.2 +/- 1.1 years [95 % confidence interval (CI) 66.2-70.3, n = 62], which was significantly earlier than the AAO for the non-TBI group of 70.9 +/- 0.2 years (95 % CI 70.5-71.4, n = 1197) (p = 0.013). Participants with mTBI history showed an AAO of 68.5 +/- 1.1 years (n = 56), which was significantly earlier than the AAO for the non-TBI group (p = 0.032). Participants with both MCI and mTBI showed an AAO of 66.5 +/- 1.3 years (95 % CI 63.9-69.1, n = 45), compared to 70.6 +/- 0.3 years for the non-TBI MCI group (95 % CI 70.1-71.1, n = 935) (p = 0.016). As a conclusion, a history of TBI may accelerate the AAO of cognitive impairment by two or more years. These results were consistent with reports of TBI as a significant risk factor for cognitive decline in older adults, and TBI is associated with an earlier AAO found in patients with MCI or AD. PMID- 27007485 TI - Prostate cancer, Hu antibodies and paraneoplastic neurological syndromes. AB - Prostate cancer is the most common cancer among American and European men. Nervous system affection caused by local tumor growth or osseous metastases are the main causes of neurological symptoms in prostate cancer patients. Prostate cancer is rarely reported in association with paraneoplastic neurological syndromes (PNS). We have, therefore, studied clinical and paraclinical findings of a series of patients with prostate cancer and PNS, and reviewed cases reported in the literature. Case histories of 14 patients with definite PNS from the PNS Euronetwork database and from the authors' databases were reviewed. A PubMed literature search identified 23 patients with prostate cancer and PNS. Thus, a total of 37 case histories were reviewed with respect to syndrome type, cancer evolution, paraclinical investigations, antibody status, treatment and outcome. The three most frequent isolated PNS were paraneoplastic cerebellar degeneration, paraneoplastic encephalomyelitis (PEM)/limbic encephalitis and subacute sensory neuronopathy (SSN). Onconeural antibodies were detected in 23 patients, in most cases the Hu antibody (17 patients, 74 % of all antibody-positive cases). Other well-characterized onconeural antibodies (Yo, CV2/CRMP5, amphiphysin, VGCC antibodies) were found in a minority. PNS was diagnosed prior to prostate cancer diagnosis in 50 % of the cases. The association of PNS with prostate cancer is quite infrequent, but clinically important. PNS often heralds prostate cancer diagnosis. Syndromes associated with Hu antibodies predominate. Another tumor more prone to associate with PNS should always be excluded. PMID- 27007486 TI - Severe COPD Alters Muscle Fiber Conduction Velocity During Knee Extensors Fatiguing Contraction. AB - The aim of this study was to assess the changes in muscle fiber conduction velocity (CV), as a sign of fatigue during knee extensor contraction in patients with chronic obstructive pulmonary disease (COPD) as compared with healthy controls. Eleven male patients (5 with severe and 6 with moderate COPD; age 67 +/ 5 years) and 11 age-matched healthy male controls (age 65 +/- 4 years) volunteered for the study. CV was obtained by multichannel surface electromyography (EMG) from the vastus lateralis (VL) and medialis (VM) of the quadriceps muscle during isometric, 30-second duration knee extension at 70% of maximal voluntary contraction. The decline in CV in both the VL and VM was steeper in the severe COPD patients than in healthy controls (for VL: severe COPD vs. controls -0.45 +/- 0.07%/s; p < 0.001, and for VM: severe COPD vs. controls 0.54 +/- 0.09%/s, p < 0.001). No difference in CV decline was found between the moderate COPD patients and the healthy controls. These findings suggest that severe COPD may impair muscle functions, leading to greater muscular fatigue, as expressed by CV changes. The results may be due to a greater involvement of anaerobic metabolism and a shift towards fatigable type II fibers in the muscle composition of the severe COPD patients. PMID- 27007487 TI - Controlling the Cavity Structures of Two-Photon-Pumped Perovskite Microlasers. AB - Low-threshold two-photon-pumped (TPP) perovskite microcavity lasers are achieved in crystal perovskite 1D or 2D microstructures fabricated through a liquid-phase self-assembly method assisted by two distinct surfactant soft templates. The lasing actions from the perovskite materials exhibit a shape-dependent microcavity effect, which is subsequently utilized for the modulation of the lasing modes and for the achievement of two-photon-pumped single-mode perovskite microlasers. PMID- 27007488 TI - Are we talking the same paradigm? Considering methodological choices in health education systematic review. AB - For the past two decades, there have been calls for medical education to become more evidence-based. Whilst previous works have described how to use such methods, there are no works discussing when or why to select different methods from either a conceptual or pragmatic perspective. This question is not to suggest the superiority of such methods, but that having a clear rationale to underpin such choices is key and should be communicated to the reader of such works. Our goal within this manuscript is to consider the philosophical alignment of these different review and synthesis modalities and how this impacts on their suitability to answer different systematic review questions within health education. The key characteristic of a systematic review that should impact the synthesis choice is discussed in detail. By clearly defining this and the related outcome expected from the review and for educators who will receive this outcome, the alignment will become apparent. This will then allow deployment of an appropriate methodology that is fit for purpose and will indeed justify the significant work needed to complete a systematic. Key items discussed are the positivist synthesis methods meta-analysis and content analysis to address questions in the form of 'whether and what' education is effective. These can be juxtaposed with the constructivist aligned thematic analysis and meta-ethnography to address questions in the form of 'why'. The concept of the realist review is also considered. It is proposed that authors of such work should describe their research alignment and the link between question, alignment and evidence synthesis method selected. The process of exploring the range of modalities and their alignment highlights gaps in the researcher's arsenal. Future works are needed to explore the impact of such changes in writing from authors of medical education systematic review. PMID- 27007489 TI - An opportunity to combat obesity lies in the at-risk college population. AB - PURPOSE: Approximately 70% of United States [or U.S.] adults are either overweight or obese. Obesity increases the risk of chronic disease and strains healthcare access, quality, and cost. Weight gain occurs in college students threatening optimal weight maintenance. Physical activity is fundamental to preventing disease. College students incur multiple challenges in weight management. The purpose of the article is to describe the opportunity for Advanced Practice Registered Nurses (APRNs) to intentionally become wellness promoters. DATA SOURCES: The literature was reviewed and interventions developed. Guided by Bandura's Social Cognitive Theory, focus was concentrated on environmental influences through a proposed Staying Active Campaign (SAC). CONCLUSIONS: College students are a vulnerable population at risk for unhealthful practices. Young adulthood is a critical period of weight gain that carries risk for later adulthood. College students desire and require assistance for successful weight management. Interventions can be directed by APRNs to achieve healthful weight management and create a campus-wide culture that reinforces healthful practices. IMPLICATIONS FOR PRACTICE: Obesity in the college population is a twofold circumstance. Action by APRNs is needed to address obesity and advocate for the prevention of future obesity. The SAC decreases the confounding college environment and supports the students' ability to be physically active while establishing personal lifelong behaviors to emulate and share with others. PMID- 27007490 TI - Designing Au Surface-Modified Nanoporous-Single-Crystalline SrTiO3 to Optimize Diffusion of Surface Plasmon Resonance-Induce Photoelectron toward Enhanced Visible-Light Photoactivity. AB - Nanoporous single-crystalline SrTiO3 is fabricated at a low temperature of 60 degrees C via a novel approach of sol-gel alkali-dissolution-exothermal reaction. The plasmon-active metal Au is loaded on the nanoporous single-crystalline SrTiO3 material to construct a new kind of plasmonic photocatalyst. Due to the single crystalline nature and the space confinement effect of pores for Au growing, not only the promoted diffusion efficiency of surface plasmon resonance (SPR)-induce photoelectron is achieved, but also the diffusion region are well optimized via changing the loading amount of Au. Therefore, an optimal sample with 4.8 wt % Au loading exhibits a more than 40-fold photoactivity enhancement under visible light irradiation compared to the common nanosized SrTiO3 (a commercially available sample) loaded with 5.3 wt % Au which was prepared under the same condition. Furthermore, combining the special nanostructure of Au surface modified nanoporous-single-crystalline SrTiO3 with photocatalytic properties, estimation of the diffusion mean free path of SPR-induce photoelectron can be achieved. This study proposes an alternative approach to enhance the photoactivity of plasmonic photocatalyst via fine designing the semiconductor substrate. PMID- 27007491 TI - Lynch syndrome in South America: past, present and future. AB - After decades of unawareness about Lynch syndrome, the medical community in South America is increasingly interested and informed. The visits and support of mentors like H. T. Lynch had been crucial to this awakening. Several countries have at least one registry with skilled personnel in genetic counseling and research. However, this only represents a very restricted resource for the region. According to the GETH, there are 27 hereditary cancer care centers in South America (21 in Brazil, 3 in Argentina, 1 in Uruguay, 1 in Chile and 1 in Peru). These registries differ in fundamental aspects of function, capabilities and funding, but are able to conduct high quality clinical, research and educational activities due to the dedication and personal effort of their members, and organizational support. More support from the governments as well as the participation of the community would boost the initiatives of people leading these groups. Meantime, the collaboration among the South American registries and the involvement of registries and leaders from developed countries will allow to maximize the efficiency in caring for affected patients and their families. The aim of this article is to describe how the knowledge of LS began to be spread in South America, how the first registries were organized and to summarize the current state of progress. In addition, we will provide an update of the clinical and molecular findings in the region. PMID- 27007492 TI - Pancarpal Arthrodesis Without Rigid Coaptation Using the Hybrid Dynamic Compression Plate in Dogs. AB - OBJECTIVE: To describe the complications, short- and long-term outcomes, and owner satisfaction for dogs treated with pancarpal arthrodesis (PCA) using the 2.7/3.5 mm locking and dynamic compression plate (DCP) hybrid pancarpal arthrodesis plate (hybrid DCP [HDCP]) without rigid coaptation in the postoperative period. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs with carpal injuries requiring PCA (n=15). METHODS: Records (May 2007-October 2013) of dogs that had PCA using 3.5/2.7 mm HDCP (1 or 2 plates) and a Robert-Jones bandage were reviewed to determine intra- and post-operative complications and overall limb function. Follow-up was obtained by clinical evaluation at our institution and telephone interview of owners. RESULTS: Fourteen dogs had PCA stabilized with a single HDCP and 1 giant breed dog had PCA stabilized with 2 HDCP on the dorsal aspect of the carpus secured onto the 3rd and 4th metacarpal bones. Two dogs presented with bilateral injuries. Thirteen owners (87%) judged the results of surgery as excellent and 2 (13%) judged the results of surgery as good. Minor complications (4 limbs; 23%) were occasional episodes of mild lameness in 3 dogs and 3 episodes of discharging sinus tracts in a single dog. Major complications (3 limbs; 17%) included 1 surgical site infection and implant failure in a 43 kg dog with an active leishmaniasis infection and a concurrent bilateral sacro-iliac luxation. Two dogs developed episodes of discharging sinus tract and pain over the most distal screw that eventually necessitated plate removal. CONCLUSION: PCA without rigid coaptation can successfully be performed using the HDCP. PMID- 27007493 TI - Polymorphism of Phosphine-Protected Gold Nanoclusters: Synthesis and Characterization of a New 22-Gold-Atom Cluster. AB - A new Au22 nanocluster, protected by bis(2-diphenyl-phosphino)ethyl ether (dppee or C28 H28 OP2 ) ligand, has been synthsized and purified with high yield. Electrospray mass spectrometry shows that the new cluster has a formula of Au22 (dppee)7 , containing 22 gold atoms and seven dppee ligands. The cluster is found to be stable as a solid, but metastable in solution. The new cluster has been characterized by UV-Vis-NIR absorption spectroscopy, collision-induced dissociation, and (31) P-NMR. The properties of the new cluster have been compared with the previous Au22 (dppo)6 nanocluster (dppo = 1,8-bis(diphenyl phosphino)octane or C32 H36 P2 ), which contains two fused Au11 units. All the experimental data indicate that the new Au22 (dppee)7 cluster is different from the previously known Au22 (dppo)6 cluster and represents a new Au22 core, which contains most likely one Au11 motif with several Au2 (dppee) or Au(dppee) units. The Au22 (dppee)7 cluster provides a new example of the ligand effects on the nuclearity and structural polymorphism of phosphine-protected atom-precise gold nanoclusters. PMID- 27007494 TI - Open field study on the efficacy of oral fluralaner for long-term control of flea allergy dermatitis in client-owned dogs in Ile-de-France region. AB - BACKGROUND: Fluralaner is the first orally administered isoxazoline to provide 12 weeks of activity against fleas and ticks after a single administration. As a result of its potent anti-flea activity, oral fluralaner may be proposed as a component of a strategy for the control of flea allergy dermatitis (FAD) in dogs. The open field study reported here assessed the efficacy of fluralaner for long term control (up to 6 months) of FAD in affected client-owned dogs maintained under common household conditions in the Ile-de-France region. METHODS: This was an open pre-treatment versus post-treatment study. Client-owned dogs with clinical signs of FAD were recruited and treated with oral fluralaner (Bravecto(r)) at 25-56 mg/kg body weight on days 0 and 84. The dogs' condition was assessed at each visit (on days 0, 28, 84 and 168) using the following three parameters: (i) extent of skin lesions based on the scoring system for canine FAD; (ii) pruritus severity based on the pruritus visual analog scale; (iii) presence or absence of fleas or flea feces. RESULTS: Of the 26 dogs initially enrolled, 23 were presented on day 28, 20 on day 84 and 16 for the final evaluation on day 168. Eighteen out of 20 dogs (90 %) presented on day 84 and 15 out of 16 dogs (94 %) presented on day 168 showed a complete clinical resolution. The post-treatment FAD clinical scores on days 28, 84 and 168 were significantly different from that of the pre-treatment with a reduction of 89.8 %, 98.8 % and 99.8 %, respectively. The post-treatment pruritus index values on days 28, 84 and 168 were significantly different from that of the pre-treatment with a reduction of 45.2 %, 71.2 % and 80.8 %, respectively. CONCLUSIONS: The present study confirmed that oral fluralaner treatment should be considered as effective for long-term control of clinical signs in FAD affected dogs. PMID- 27007495 TI - Current role of selective internal radiation with yttrium-90 in liver tumors. AB - An expert panel met to review the evidence for selective internal radiation therapy (SIRT) using yttrium-90 microspheres in hepatocellular carcinoma and metastases from colorectal cancer and neuroendocrine tumors. There is now convincing evidence for the safety and efficacy of SIRT in these situations albeit mostly from retrospective cohort studies. There are a number of ongoing prospective randomized controlled clinical trials investigating the role of SIRT in liver tumors; however, data from these trials are still several years away (although the SIRFLOX study has been recently published). In this evolving environment, published evidence and the authors' experience were used to summarize the current and potential role of SIRT in the management of hepatocellular carcinoma of intermediate or advanced stage and in liver-dominant metastatic colorectal cancer and metastatic neuroendocrine tumors. PMID- 27007496 TI - A novel genetic engineering platform for the effective management of biological contaminants for the production of microalgae. AB - Microalgal cultivation that takes advantage of solar energy is one of the most cost-effective systems for the biotechnological production of biofuels, and a range of high value products, including pharmaceuticals, fertilizers and feed. However, one of the main constraints for the cultivation of microalgae is the potential contamination with biological pollutants, such as bacteria, fungi, zooplankton or other undesirable microalgae. In closed bioreactors, the control of contamination requires the sterilization of the media, containers and all materials, which increases the cost of production, whereas open pond systems severely limits the number of species that can be cultivated under extreme environmental conditions to prevent contaminations. Here, we report the metabolic engineering of Chlamydomonas reinhardtii to use phosphite as its sole phosphorus source by expressing the ptxD gene from Pseudomonas stutzeri WM88, which encodes a phosphite oxidoreductase able to oxidize phosphite into phosphate using NAD as a cofactor. Engineered C. reinhardtii lines are capable of becoming the dominant species in a mixed culture when fertilized with phosphite as a sole phosphorus source. Our results represent a new platform for the production of microalgae, potentially useful for both closed photobioreactors and open pond systems without the need for using sterile conditions nor antibiotics or herbicides to prevent contamination with biological pollutants. PMID- 27007497 TI - Adolescent bystanders' perspectives of aggression in the online versus school environments. AB - Researchers' understanding of bystanders' perspectives in the cyber-environment fails to take young people's perceptions into account and remains imperfect. Interventions encouraging adolescents to help targets of cyber-aggression are therefore typically based upon traditional school-based aggression research. Twenty-four in-depth interviews with Australian 13-16 year-olds revealed two themes that reflect how young bystanders perceive differences between aggression online and at school. The physical presence theme suggests that young bystanders struggle to determine online intentions in the absence of body language, leading to hesitancy in reactions and furthermore make it easier for them to ignore online transgressions and avoid becoming involved. The authority theme indicates young bystanders perceive that, compared to the school environment, the online environment lacks clearly established rules, authority figures and formal reporting mechanisms. These differences indicate that unique strategies should be developed to encourage young bystanders to intervene in cyber-aggression situations. PMID- 27007498 TI - The role of intergenerational similarity and parenting in adolescent self criticism: An actor-partner interdependence model. AB - Research investigating the development of adolescent self-criticism has typically focused on the role of either parental self-criticism or parenting. This study used an actor-partner interdependence model to examine an integrated theoretical model in which achievement-oriented psychological control has an intervening role in the relation between parental and adolescent self-criticism. Additionally, the relative contribution of both parents and the moderating role of adolescent gender were examined. Participants were 284 adolescents (M = 14 years, range = 12 16 years) and their parents (M = 46 years, range = 32-63 years). Results showed that only maternal self-criticism was directly related to adolescent self criticism. However, both parents' achievement-oriented psychological control had an intervening role in the relation between parent and adolescent self-criticism in both boys and girls. Moreover, one parent's achievement-oriented psychological control was not predicted by the self-criticism of the other parent. PMID- 27007499 TI - Robust Stimulation of W1282X-CFTR Channel Activity by a Combination of Allosteric Modulators. AB - W1282X is a common nonsense mutation among cystic fibrosis patients that results in the production of a truncated Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Here we show that the channel activity of the W1282X CFTR polypeptide is exceptionally low in excised membrane patches at normally saturating doses of ATP and PKA (single channel open probability (PO) < 0.01). However, W1282X-CFTR channels were stimulated by two CFTR modulators, the FDA approved VX-770 and the dietary compound curcumin. Each of these compounds is an allosteric modulator of CFTR gating that promotes channel activity in the absence of the native ligand, ATP. Although W1282X-CFTR channels were stimulated by VX 770 in the absence of ATP their activities remained dependent on PKA phosphorylation. Thus, activated W1282X-CFTR channels should remain under physiologic control by cyclic nucleotide signaling pathways in vivo. VX-770 and curcumin exerted additive effects on W1282X-CFTR channel gating (opening/closing) in excised patches such that the Po of the truncated channel approached unity (> 0.9) when treated with both modulators. VX-770 and curcumin also additively stimulated W1282X-CFTR mediated currents in polarized FRT epithelial monolayers. In this setting, however, the stimulated W1282X-CFTR currents were smaller than those mediated by wild type CFTR (3-5%) due presumably to lower expression levels or cell surface targeting of the truncated protein. Combining allosteric modulators of different mechanistic classes is worth considering as a treatment option for W1282X CF patients perhaps when coupled with maneuvers to increase expression of the truncated protein. PMID- 27007500 TI - Costs and returns on training investment for empirically supported psychological interventions. AB - Objective Financial costs are a significant barrier to the uptake of empirically supported psychological interventions in clinical settings. Training may be among the largest of these costs; however, the potential magnitude of these costs is unclear. The aim of the present study was to develop a hypothetical model of potential training costs associated with adopting a novel therapy using systematic review of anticipated training durations and publicly available data on workshop costs, training materials and income. Methods Direct and indirect costs were estimated for reference categories being cognitive behavioural therapy for social anxiety disorder delivered by registered psychologists. These were based on averages of 39 workshops and eight treatment manuals available in Australia identified through online searches. Results This model demonstrated that upper cost ranges for training can exceed A$55000, and even didactic training (reading manuals, attending workshops) may cost up to A$9000. Indirect costs of forfeited income account for a substantial proportion of these costs. Conclusions This hypothetical model highlights why training costs should be considered in decisions about disseminating and implementing novel empirically supported psychological interventions, particularly within private workforces. In addition, the direct return on training investment for practitioners in private practice is unclear, and may vary based on caseloads and current treatment modalities. Initiatives to track competence, support training and identify novel training solutions may be required to ensure the sustainability of high-quality mental healthcare. What is known about the topic? Financial costs are one of the leading factors determining whether empirically supported mental health treatments are adopted or sustained. Training costs may be one of the largest costs of disseminating and implementing novel psychological therapies within existing workforces, including both direct (e.g. workshop fees) and indirect (e.g. lost income) costs. However, little is understood about the potential magnitude of these costs. What does this paper add? This paper presents a hypothetical modelling of potential costs associated with adopting a novel therapy, with reference categories for an empirically supported treatment (cognitive behaviour therapy) for one mental disorder (social anxiety disorder) for one mental health profession (psychologist). This model was developed and populated using systematic review of anticipated training durations and publicly available data on workshop costs, training materials and income. What are the implications for practitioners? With potential costs for adopting one novel psychological intervention exceeding A$55000, we highlight why training costs and pathways should be a focal point for ensuring the sustainable provision of high quality mental healthcare in Australia. PMID- 27007502 TI - Gallium Nitride Crystals: Novel Supercapacitor Electrode Materials. AB - A type of single-crystal gallium nitride mesoporous membrane is fabricated and its supercapacitor properties are demonstrated for the first time. The supercapacitors exhibit high-rate capability, stable cycling life at high rates, and ultrahigh power density. This study may expand the range of crystals as high performance electrode materials in the field of energy storage. PMID- 27007501 TI - Maternal Antibody-Mediated Disease Enhancement in Type I Interferon-Deficient Mice Leads to Lethal Disease Associated with Liver Damage. AB - Epidemiological studies have reported that most of the severe dengue cases occur upon a secondary heterologous infection. Furthermore, babies born to dengue immune mothers are at greater risk of developing severe disease upon primary infection with a heterologous or homologous dengue virus (DENV) serotype when maternal antibodies reach sub-neutralizing concentrations. These observations have been explained by the antibody mediated disease enhancement (ADE) phenomenon whereby heterologous antibodies or sub-neutralizing homologous antibodies bind to but fail to neutralize DENV particles, allowing Fc-receptor mediated entry of the virus-antibody complexes into host cells. This eventually results in enhanced viral replication and heightened inflammatory responses. In an attempt to replicate this ADE phenomenon in a mouse model, we previously reported that upon DENV2 infection 5-week old type I and II interferon (IFN) receptors-deficient mice (AG129) born to DENV1-immune mothers displayed enhancement of disease severity characterized by increased virus titers and extensive vascular leakage which eventually led to the animals' death. However, as dengue occurs in immune competent individuals, we sought to reproduce this mouse model in a less immunocompromised background. Here, we report an ADE model that is mediated by maternal antibodies in type I IFN receptor-deficient A129 mice. We show that 5 week old A129 mice born to DENV1-immune mothers succumbed to a DENV2 infection within 4 days that was sub-lethal in mice born to naive mothers. Clinical manifestations included extensive hepatocyte vacuolation, moderate vascular leakage, lymphopenia, and thrombocytopenia. Anti-TNFalpha therapy totally protected the mice and correlated with healthy hepatocytes. In contrast, blocking IL-6 did not impact the virus titers or disease outcome. This A129 mouse model of ADE may help dissecting the mechanisms involved in dengue pathogenesis and evaluate the efficacy of vaccine and therapeutic candidates. PMID- 27007503 TI - Quantification of tunicamycin-induced protein expression and N-glycosylation changes in yeast. AB - Tunicamycin is a potent protein N-glycosylation inhibitor that has frequently been used to manipulate protein glycosylation in cells. However, protein expression and glycosylation changes as a result of tunicamycin treatment are still unclear. Using yeast as a model system, we systematically investigated the cellular response to tunicamycin at the proteome and N-glycoproteome levels. By utilizing modern mass spectrometry-based proteomics, we quantified 4259 proteins, which nearly covers the entire yeast proteome. After the three-hour tunicamycin treatment, more than 5% of proteins were down-regulated by at least 2 fold, among which proteins related to several glycan metabolism and glycolysis-related pathways were highly enriched. Furthermore, several proteins in the canonical unfolded protein response pathway were up-regulated because the inhibition of protein N-glycosylation impacts protein folding and trafficking. We also comprehensively quantified protein glycosylation changes in tunicamycin-treated cells, and more than one third of quantified unique glycopeptides (168 of 465 peptides) were down-regulated. Proteins containing down-regulated glycopeptides were related to glycosylation, glycoprotein metabolic processes, carbohydrate processes, and cell wall organization according to gene ontology clustering. The current results provide the first global view of the cellular response to tunicamycin at the proteome and glycoproteome levels. PMID- 27007504 TI - Li3Cs2M2B3P6O24 (M = Pb, Sr): borophosphates with double six-membered ring of [BP2O8](3.). AB - New borophosphates Li3Cs2M2B3P6O24 (M = Pb, Sr) have been synthesized by high temperature solid-state reactions. The single-crystal X-ray diffraction data reveal their non-centrosymmetric cubic space group P213 and lattice parameters of a = 12.7246(3) A and 12.687(2) A and V = 2060.31(8) A(3) and 2042.3(4) A(3) for Li3Cs2Pb2B3P6O24 and Li3Cs2Sr2B3P6O24, respectively. They are three-dimensional (3D) [BP2O8](3-)infinity anionic frameworks formed by a new double six-membered ring building unit consisting of BO4 and PO4 units joined alternately. Interestingly, such a double six-membered ring is regarded as the structural variation of the 12-membered ring in the known KSrBP2O8, fusing at the BO4 tetrahedron induced by the coexistence of the Li(+) and Cs(+) cations with their large size difference. The title compounds show weak SHG intensity and exhibit photoluminescence emissions at 410 nm for Li3Cs2Pb2B3P6O24 and 440 nm for Li3Cs2Sr2B3P6O24. PMID- 27007505 TI - A review of bush dog Speothos venaticus (Lund, 1842) (Carnivora, Canidae) occurrences in Parana state, subtropical Brazil. AB - We report six new occurrence records of the bush dog Speothos venaticus, a widely distributed South American carnivore that is threatened with extinction. These records are accompanied by notes on the places where the records were made, such as vegetation type, date and information about the protection of areas. The records, obtained over the last 17 years in Parana state, southern Brazil, offer an improved understanding of the species geographic range and the threats it faces and can enable better assessments of the conservation status of the species in southern Brazil. PMID- 27007506 TI - Phytoplankton composition of the water and gastrointestinal tract of the mussel Diplodon enno (Ortmann, 1921) from Sao Francisco river (Bahia, Brazil). AB - The knowledge on diet composition of the freshwater mussel Diplodon enno (Ortmann) would aid in its culture and propagation allowing, this way, the replacement of natural endangered populations in Brazil. Microalgae are the main food source for captive mussels and unionids have displayed an ability to sort algae based on the cellular characteristics prior to ingestion. The main objective of the present work is to analyze the phytoplankton composition of the water from and of the gastrointestinal contents of the mussel D. enno, as an initial step for development of a suitable rearing diet. Therefore, water samples and bivalve specimens were collected from S. Francisco River, city of Paulo Afonso, Bahia, Brazil. The microalgal composition found in water and stomach/gut content samples was very diverse being represented by the following divisions: Cyanophyta, Chlorophyta, Dinophyta and Heterokontophyta (Diatoms). Concerning the relative abundance of microalgae divisions, it is possible to state, for the water and gastrointestinal contents, that Cyanophyta represents 15% and 14%, Chlorophyta 54% in both, Heterokontophyta 31% and 27% and Dinophyta 0% and 5%, respectively. According to the Brazilian CETESB criteria for phytoplankton species classification, 50% of Cyanophyta and 15% of Chlorophyta species observed in the water samples were classified as "very frequent", as were 68% of Heterokontophyta and 33% of Chlorophyta species in the gut/stomach tract samples. Focusing at a species level, although in the water only Coelastrum sp. and Chroococcus sp. were observed in 100% and 75% of the samples, respectively, in the gastrointestinal tract the species Staurastrum sp., Aulacoseira sp., Scenedesmus sp. and Fragilaria crotonensis occurred in 80% to 100% of the samples. The present results showed that D. enno feeds not only on small chlorophytes microalgae, due to their convenient size that facilitates higher feeding rates, but also on large size diatoms, due to a possible nutritional advantage for the bivalves. Thus, a diet composed by large diatoms and small chlorophytes microalgae may be considered as the most reasonable for the maintenance of D. enno populations. PMID- 27007509 TI - Current Measures on Radioactive Contamination in Japan: A Policy Situation Analysis. AB - BACKGROUND: The Great East Japan Earthquake on 11th March 2011 and the subsequent Fukushima Dai-ichi nuclear power plant disaster caused radioactive contamination in the surrounding environment. In the immediate aftermath of the accident the Government of Japan placed strict measures on radio-contamination of food, and enhanced radio-contamination monitoring activities. Japan is a pilot country in the WHO Foodborne Disease Burden Epidemiology Reference Group (FERG), and through this initiative has an opportunity to report on policy affecting chemicals and toxins in the food distribution network. Nuclear accidents are extremely rare, and a policy situation analysis of the Japanese government's response to the Fukushima Dai-ichi nuclear accident is a responsibility of Japanese scientists. This study aims to assess Japan government policies to reduce radio-contamination risk and to identify strategies to strengthen food policies to ensure the best possible response to possible future radiation accidents. METHODS AND FINDINGS: We conducted a hand search of all publicly available policy documents issued by the Cabinet Office, the Food Safety Commission, the Ministry of Health, Labor and Welfare (MHLW), the Ministry of Agriculture, Forestry and Fishery (MAFF) and prefectural governments concerning food safety standards and changes to radiation and contamination standards since March 11th, 2011. We extracted information on food shipment and sales restrictions, allowable radio-contamination limits, monitoring activities and monitoring results. The standard for allowable radioactive cesium (Cs-134 and Cs-137) of 100 Bq/Kg in general food, 50 Bq/Kg in infant formula and all milk products, and 10 Bq/Kg in drinking water was enforced from April 2012 under the Food Sanitation Law, although a provisional standard on radio-contamination had been applied since the nuclear accident. Restrictions on the commercial sale and distribution of specific meat, vegetable and fish products were released for areas at risk of radioactive contamination. Monitoring of radioactive materials in food products in the prefectures has been mainly conducted before shipment to restrict the distribution of radio-contaminated foods. Between March 2011 and March 2012, 133,832 tests of non-commercial and commercial products were conducted, and 1,204 tests (0.9%) were found to violate the provisional standards. Since April 2012, 278,275 tests were conducted, and 2,372 tests (0.9%) were found to violate the revised standards. MHLW assessment of representative market baskets of foodstuffs at 15 locations throughout Japan between February and March 2014 found very low estimated dietary intake of radioactive cesium (0.0007-0.019 mSv/year), as did assessments of the contents of an average day's food. Monitoring of fisheries products in coastal areas affected by the nuclear accident found very limited and declining radio-contamination of live fish outside of Fukushima prefecture. Fisheries monitoring is of limited geographical scope and covers only certain fishes. CONCLUSIONS: Area-specific bans on production and distribution have been effective in preventing radioactive contamination in the Japanese food market. Currently there is no major concern about radioactive cesium concentrations in retail foodstuffs in Japan, and very low levels of contamination at the production and wholesale stage. However, because the residue limits and food safety policies were revised on an ad hoc, emergency basis after the nuclear accident, the monitoring procedure needs to be reviewed based on objective and scientifically rational criteria. A transparent and objective scientific framework is needed for prioritizing foodstuffs for inspection and revising Prefecture-specific restrictions. Monitoring of fishes and other seafood products in the wild should be regularized and the information made more publicly accessible, and monitoring activities expanded to identify foodstuffs that are no longer a food safety risk. Consultation with producers and consumers should be more formalized to ensure their concerns are incorporated into regular policy reviews in an appropriate and transparent manner. However, despite the limited available knowledge on best practice in food control and enforcement of provisional radio-contamination limits after the accident, current Japanese policy is sufficient to protect the Japanese public from major risk of radio-contamination from the commercial food market. PMID- 27007510 TI - A Cytogenomic Approach in a Case of Syndromic XY Gonadal Dysgenesis. AB - This is the first molecular characterization of a female XY patient with an Xp duplication due to an X;22 translocation. Array CGH detected a copy number gain of ~36 Mb in the Xp22.33p21.1 region involving 150 genes. Clinical and molecular studies described in the literature have suggested DAX1 duplication as the major cause responsible for a sex reversal phenotype. Additionally, the interaction between genes and their possible role in clinical features are presented to support the discussion on genotype-phenotype correlation in cases of syndromic XY gonadal dysgenesis. PMID- 27007511 TI - Cytological Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma before and after the Bethesda System for Reporting Thyroid Cytopathology. AB - BACKGROUND: The follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common subtype of papillary carcinoma after the classical variant. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has been introduced to standardize the practice of thyroid fine needle aspiration (FNA) reporting. We evaluated the impact of TBSRTC on the FNA interpretation of histologically proven FVPTCs. METHOD: Cytology reports of 455 histologically proven FVPTCs were reviewed. The rate of each TBSRTC category was compared between pre- and post-TBSRTC eras. RESULTS: The distribution of FNA diagnoses for pre-TBSRTC cases included suspicious for follicular neoplasm (SFN; n = 51, 28.7%), papillary thyroid carcinoma (PTC; n = 47, 26.4%), suspicious for malignancy (SFM; n = 32, 18%), atypia of undetermined significance (AUS; n = 23, 13%), benign (n = 18, 10.1%), and nondiagnostic (ND; n = 7, 4%). Post-TBSRTC diagnoses were: AUS (n = 68, 24.6%), PTC (n = 64, 23.1%), SFM (n = 50, 18%), SFN and benign (n = 42, 15.2%) and ND (n = 11, 4%). SFN rate decreased significantly from 28.7 to 15.2% (p = 0.001) and AUS increased from 12.9 to 24.5% (p = 0.003). CONCLUSION: Following implementation of TBSRTC, the frequency of AUS diagnoses on FNA prior to surgical resection increased. Given that the rate of FVPTC diagnoses on thyroidectomy increased over the same period, this suggests that the use of AUS has resulted in greater surgical resection of FVPTC. PMID- 27007507 TI - Using mitochondrial sirtuins as drug targets: disease implications and available compounds. AB - Sirtuins are an evolutionary conserved family of NAD(+)-dependent protein lysine deacylases. Mammals have seven Sirtuin isoforms, Sirt1-7. They contribute to regulation of metabolism, stress responses, and aging processes, and are considered therapeutic targets for metabolic and aging-related diseases. While initial studies were focused on Sirt1 and 2, recent progress on the mitochondrial Sirtuins Sirt3, 4, and 5 has stimulated research and drug development for these isoforms. Here we review the roles of Sirtuins in regulating mitochondrial functions, with a focus on the mitochondrially located isoforms, and on their contributions to disease pathologies. We further summarize the compounds available for modulating the activity of these Sirtuins, again with a focus on mitochondrial isoforms, and we describe recent results important for the further improvement of compounds. This overview illustrates the potential of mitochondrial Sirtuins as drug targets and summarizes the status, progress, and challenges in developing small molecule compounds modulating their activity. PMID- 27007512 TI - Malaria sporozoite protein expression enhances baculovirus-mediated gene transfer to hepatocytes. AB - BACKGROUND: Baculovirus vector (BV) is able to transduce foreign genes into mammalian cells efficiently and safely by incorporating a mammalian promoter. In the present study, we tailored the surface proteins expressed by malaria sporozoites to enhance hepatocyte transduction. Sporozoites infect hepatocytes within minutes of initial entry into the blood circulation. Infectivity and hepatocyte-specific selectivity are mediated by the interplay between hepatocytes and sporozoite surface proteins. The circumsporozoite protein (CSP) and the thrombospondin-related anonymous protein (TRAP) bind to the heparan sulfate proteoglycan on the hepatocyte surface and contribute to sporozoite infection and hepatocyte selectivity. METHODS: BVs displaying an ectodomain consisting of three different CSP variants (full-length, N-terminal and C-terminal) or TRAP on the virus envelope were constructed, and the resulting in vitro hepatocyte transduction efficiency was evaluated. RESULTS: We demonstrated improved hepatocyte transduction efficiency in BVs expressing CSP or TRAP ectodomains compared to BVs without malaria surface proteins. In addition, gene transduction efficiencies for BVs displaying CSP or TRAP are higher than those expressing the preS1 antigen of the hepatitis B virus. CONCLUSIONS: BVs expressing CSP or TRAP in the ectodomain could represent a promising hepatocyte-specific gene delivery methodology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27007513 TI - Effect of centrifuge test on blood serum lipids index of cadet pilots. AB - INTRODUCTION AND OBJECTIVE: This study aimed at investigating the relationship between the lipid index (WS) in the examined cadets and duration of exposure to +Gz in the human centrifuge. MATERIALS AND METHODS: The study involved 19 first year cadets of the Polish Air Force Academy in Deblin. Tests in the human centrifuge were repeated twice, i.e. prior to (test I) and 45 days after (test II). After exposure to +Gz, the examined cadets were divided into 2 groups. Group I (N=11) included cadets subjected to a shorter total duration of exposure to +Gz, while group II (N=8) included cadets with a longer total duration of exposure to +Gz. Total cholesterol (TC), high density lipoprotein (HDL), triglycerides (TG), and apolipoproteins A1 and B were assayed in blood serum prior to (assay A) and after (assay B) both exposures to +Gz. Low density lipoprotein (LDL) level was estimated from the Friedewald formula. WS is an own mathematical algorithm. RESULTS: WS was higher in group II, assay A - 10.0 and B 10.08 of test I in the human centrifuge than in group I where the WS values were 6.91 and 6.96, respectively. WS was also higher in group II in assay A - 10.0 and B -10.1 of test II in the human centrifuge than in group I - 6.96 and 6.80, respectively. CONCLUSIONS: The higher value of WS in group II, both after the first and second exposure to +Gz in human centrifuge, in comparison with group I, indicated its usefulness for determination of the maximum capability of applying acceleration of the interval type during training in the human centrifuge. PMID- 27007508 TI - Mechanisms of long noncoding RNA function in development and disease. AB - Since decades it has been known that non-protein-coding RNAs have important cellular functions. Deep sequencing recently facilitated the discovery of thousands of novel transcripts, now classified as long noncoding RNAs (lncRNAs), in many vertebrate and invertebrate species. LncRNAs are involved in a wide range of cellular mechanisms, from almost all aspects of gene expression to protein translation and stability. Recent findings implicate lncRNAs as key players of cellular differentiation, cell lineage choice, organogenesis and tissue homeostasis. Moreover, lncRNAs are involved in pathological conditions such as cancer and cardiovascular disease, and therefore provide novel biomarkers and pharmaceutical targets. Here we discuss examples illustrating the versatility of lncRNAs in gene control, development and differentiation, as well as in human disease. PMID- 27007514 TI - Pantoea agglomerans: a mysterious bacterium of evil and good. Part II- Deleterious effects: Dust-borne endotoxins and allergens--focus on grain dust, other agricultural dusts and wood dust. AB - Pantoea agglomerans, a Gram-negative bacterium developing in a variety of plants as epiphyte or endophyte is particularly common in grain and grain dust, and has been identified by an interdisciplinary group from Lublin, eastern Poland, as a causative agent of work-related diseases associated with exposure to grain dust and other agricultural dusts. The concentration of P. agglomerans in grain as well as in the settled grain and flour dust was found to be high, ranging from 10(4)-10(8) CFU/g, while in the air polluted with grain or flour dust it ranged from 10(3)-10(5) CFU/m(3) and formed 73.2-96% of the total airborne Gram-negative bacteria. The concentration of P. agglomerans was also relatively high in the air of the facilities processing herbs and other plant materials, while it was lower in animal farms and in wood processing facilities. Pantoea agglomerans produces a biologically-potent endotoxin (cell wall lipopolysaccharide, LPS). The significant part of this endotoxin occurs in dusts in the form of virus-sized globular nanoparticles measuring 10-50 nm that could be described as the 'endotoxin super-macromolecules'. A highly significant relationship was found (R=0.804, P=0.000927) between the concentration of the viable P. agglomerans in the air of various agricultural and wood industry settings and the concentration of bacterial endotoxin in the air, as assessed by the Limulus test. Although this result may be interfered by the presence of endotoxin produced by other Gram negative species, it unequivocally suggests the primary role of the P. agglomerans endotoxin as an adverse agent in the agricultural working environment, causing toxic pneumonitis (ODTS). Numerous experiments by the inhalation exposure of animals to various extracts of P. agglomerans strains isolated from grain dust, including endotoxin isolated with trichloroacetic acid (LPS-TCA), endotoxin nanoparticles isolated in sucrose gradient (VECN), and mixture of proteins and endotoxin obtained by extraction of bacterial mass in saline (CA-S), showed the ability of these extracts to evoke inflammatory and fibrotic changes in the lungs, to stimulate alveolar macrophages to produce superoxide anion (O2(-)), interleukin-1 (IL-1) and chemotactic factors for other macrophages and neutrophils, and to increase the pulmonary concentrations of toll like receptors and chemokines. The most potent properties showed the CA-S which may be attributed to the allergenic properties of P. agglomerans proteins enhanced by the presence of the autologous endotoxin. The results of these experiments are in accord with the clinical studies which revealed a high reactivity of the agricultural and grain industry workers to allergenic extracts of P. agglomerans, and the presence in these populations of hypersensitivity pneumonitis and asthma cases caused by this bacterium. P. agglomerans has been also identified as a potential causative agent of allergic dermatitis in farmers and of allergic pulmonary disorders in cattle. In conclusion, similar to the cotton industry, also in the grain industry and in agriculture, Pantoea agglomerans should be regarded as one of the major causative agents of work related diseases, caused by the adverse effects of protein allergens and endotoxin produced by this bacterium. PMID- 27007515 TI - Microarrays--new possibilities for detecting biological factors hazardous for humans and animals, and for use in environmental protection. AB - Both the known biological agents that cause infectious diseases, as well as modified (ABF-Advanced Biological Factors) or new, emerging agents pose a significant diagnostic problem using previously applied methods, both classical, as well as based on molecular biology methods. The latter, such as PCR and real time PCR, have significant limitations, both quantitative (low capacity), and qualitative (limited number of targets). The article discusses the results of studies on using the microarray method for the identification of viruses (e.g. Orthopoxvirus group, noroviruses, influenza A and B viruses, rhino- and enteroviruses responsible for the FRI (Febrile Respiratory Illness), European bunyaviruses, and SARS-causing viruses), and bacteria (Mycobacterium spp., Yersinia spp., Campylobacter spp., Streptococcus pneumoniae, Salmonella typhi, Salmonella enterica, Staphylococcus aureus, Neisseria meningitidis, Clostridium difficile , Helicobacter pylori), including multiple antibiotic-resistant strains. The method allows for the serotyping and genotyping of bacteria, and is useful in the diagnosis of genetically modified agents. It allows the testing of thousands of genes in one experiment. In addition to diagnosis, it is applicable for gene expression studies, analysis of the function of genes, microorganisms virulence, and allows the detection of even single mutations. The possibility of its operational application in epidemiological surveillance, and in the detection of disease outbreak agents is demonstrated. PMID- 27007516 TI - Obesity and renal cancer incidence and mortality--a systematic review of prospective cohort studies. AB - INTRODUCTION AND OBJECTIVE: There have been many studies published recently on obesity and the risk of renal cancer; however, the epidemiological evidence for such an association has not been consistent. Therefore, a systematic review was conducted of the prospective cohort studies to assess the association between obesity and the risk of renal cancer incidence and death. MATERIALS AND METHODS: A search was conducted of the PubMed database and references to published studies from inception until May 2013. Guidelines for Assessing Quality in Prognostic Studies on the Basis of Framework for Potential Biases were followed for quality assessment of studies included in the systematic review. RESULTS: Twenty eligible studies were identified and included in the systematic review. Among the 20 selected studies, overall study quality was high. Although the evidence from the prospective cohort studies, linking obesity with renal cancer incidence, has not been entirely consistent, there is a convincing body of data for a positive relationship. Moreover, cumulative data is compelling for a strong positive association between obesity and fatal renal cancer. CONCLUSIONS: There is a relatively consistent amount of evidence that obesity increases the risk of renal cancer and fatal renal cancer. Further research is needed as better understanding of mechanisms by which obesity may influence renal cancer development and progression will aid the fostering of strategies for prevention and treatment of one of the most lethal human malignancies. PMID- 27007517 TI - Microbial contamination level of air in animal waste utilization plants. AB - OBJECTIVE: The aim of this research was evaluation of microbial contamination of air within and in the vicinity of animal waste disposal plants. MATERIALS AND METHOD: Air samples were analyzed to determine total bacterial and fungal counts as well as microbial species composition. Measurements of climate conditions (temperature, humidity, air motion) and total dust concentration were also performed. RESULTS: Total numbers of bacteria and fungi surpassed the threshold limit values for production halls. The most abundant bacteria detected were those consisting of physiological microflora of animal dermis and mucosa. Fungal species composition proved to be most differentiated in the air beyond the plant area. Aspergillus versicolor, a pathogenic and allergenic filamentous fungus, was isolated only inside the rendering plant processing hall. CONCLUSIONS: The measurement results showed a low sanitary-hygienic state of air in the plant processing halls and substantial air pollution in its immediate vicinity. PMID- 27007518 TI - Identification of host blood-meal sources and Borrelia in field-collected Ixodes ricinus ticks in north-western Poland. AB - Forest animals play fundamental roles in the maintenance of Ixodes ricinus and Borrelia species in the forest biotope. To identify the forest vertebrate species that are host for I. ricinus and for the recognition of the reservoirs of Borrelia species, the blood-meal of 325 I. ricinus ticks collected at two forest sites in north-western Poland were analysed. Nested PCR was used to detect polymorphisms in a fragment of the mitochondrial 12S rRNA gene for the identification of the hosts species. The products were digested with the restriction enzymes, a combination that allows the identification of 60 vertebrate species, comprising 17 bird, 4 reptile and 39 mammalian species. Host DNA was detected in 244 (75%) I. ricinus individuals, with the species being detected and classified for 210 (86%) samples. The restriction patterns resulted in the identification of 14 vertebrate species, including 2 species of birds, lizard, badger, rabbit, deer; most of the samples contained DNA from wild boar (Sus scrofa), red fox (Vulpes vulpes), red deer (Cervus elaphus) and roe deer (Capreolus capreolus). Identification of Borrelia species was based on the flaB gene using nested PCR coupled to RFLP. This method allows the identification of all Borrelia species transmitted by I. ricinus in Europe, including B. miyamotoi and 3 genetic variants of B. garinii. In the studied isolates, 2 species belonging to B. burgdorferi sensu lato were identified--B. garinii and B. afzelii, and B. miyamotoi, which are related to relapsing fever borreliae. PMID- 27007519 TI - Expansion and aerobiology of Ambrosia artemisiifolia L. in Slovakia. AB - INTRODUCTION AND OBJECTIVE: The invasive alien species Ambrosia artemisiifolia cause environmental, agronomical and medical problems in many regions of the world, including Slovakia. The purpose of this study was to survey the spread and distribution of this species in Slovakia and to analyse its airborne pollen pattern. MATERIALS AND METHODS: To evaluate the spatiotemporal dynamics of Ambrosia invasion in the territory of Slovakia, herbarium specimens, published databases and field investigations were considered. Aerobiological sampling was based on the analysis of pollen records at five aerobiological stations in Slovakia. For Bratislava and Banska Bystrica Monitoring stations, trends in Ambrosia pollen seasons were determined using Mann-Kendall test and Sen's slope estimator. RESULTS: Since the first record of A. artemisiifolia in Slovakia, the number of its colonies and its spread rate has increased considerably, and the colonisation of this species has been successful mainly in the south-western part of the country. Highest airborne pollen counts were recorded in Nitra, Trnava and Bratislava Monitoring Stations situated in the areas most infested by A. artemisiifolia in Slovakia. However, high pollen counts were also noted in Banska Bystrica and Kosice Monitoring Stations situated in areas where the source species was less abundant. During the study period, the number of days on which the pollen concentration exceeded the threshold of sensitivity increased significantly (+1.33 days/year) in Banska Bystrica, whereas the peak value decreased significantly (-13.37 pollen/year) in Bratislava. CONCLUSION: The number of the populations of A. artemisiifolia has increased considerably in recent years. Besides the most infested areas, high airborne pollen counts were also recorded in territories where the plant species was less abundant. During the study period, the intensity of Ambrosia pollen seasons decreased in Bratislava, probably due to changes in land-use practices, while the increasing trend in the pollen seasons intensity in Banska Bystrica mainly reflects the situation in the ragweed-infested remote areas due to long-range pollen transport. PMID- 27007521 TI - Detection of CHLAMYDIA PSITTACI in feral pigeons (COLUMBA LIVIA DOMESTICA) in Slovakia and their characterisation. AB - INTRODUCTION AND OBJECTIVES: Chlamydia psittaci, an obligate intracellular bacterium, which is the etiologic agent of avian chlamydiosis in birds and ornithosis/psittacosis in humans, has been reported to be one of the most common pathogens found in feral pigeons worldwide, and thus constitutes a zoonotic risk. The aim of the study was to investigate pigeons in Slovakia living in areas in close proximity to humans for the presence of C. psittaci, using pharyngeal and cloacal swabs. MATERIAL AND METHODS: 122 clinically healthy pigeons from different geographical regions of Slovakia were examined for the presence of C. psittaci. The adult pigeons of both genders were captured during the summer period in the urban centres of Slovakian towns. Each sample was examined by molecular method PCR, and in the case of positive result the identity of the obtained sequence was examined by a BLAST search. RESULTS: Of the total number of 244 examined samples, 14 (5.7%) showed positivity for C. psittaci infection, 5 of which were from pharyngeal swabs (4.1%) and 9 from cloacal swabs (7.4%). A positive result was detected in 13 pigeons (10.7%). Phylogenetic analysis showed that all the positive samples are genetically very close to genotypes B and genotype E. CONCLUSION: Phylogenetic examination of the 14 isolates of C. psittaci identified in the presented study, based on 23S rRNA gene sequence, revealed their close relationship with C. psittaci genotypes B and E. Both genotypes are predominantly prevalent in pigeons and both can be transmitted to humans. Therefore, it is necessary to perform screening examinations of animals and analyse the epidemiological factors affecting the way of transmission and circulation of pathogen. PMID- 27007520 TI - Analysis of seroprevalence against Coxiella burnetii in a sample of farm workers in Western Sicily. AB - INTRODUCTION AND OBJECTIVE: Little is known about the development of chronic Q fever caused by Coxiella burnetii in occupational risk groups and in the general population in Italy, as well as in many countries in the world. The aim of this study was to highlight the presence of the infection in a sample of workers operating outdoors (but not directly in contact with animals), in three provinces of western Sicily, in order to detect the human seroprevalence and compare the obtained data with those found in animals raised in the same territory. MATERIALS AND METHODS: The study included 126 generic seasonal agricultural workers (labourers), 84 male and 42 female; none of whom were aware of any previous contact with Coxiella burnetii. Their immunologic status against Coxiella burnetii was tested through research and titration of both phases I and II specific antibodies (IgG) with an indirect immunofluorescence assay, using anti antibodies labeled with fluorescein isothiocyanate. All data were statistically analyzed, comparing all positive results from the three provinces through variance analysis, and then comparing human results with those obtained from animals raised in the considered areas, specifically, 1,511 cows, 46 of which were found positive (3.04%), and 3,391 sheep, 548 of which were found positive (16.16%). RESULTS: Anti-Coxiella antibodies were found in nine of 42 females sampled (21.4%; 95%CI=[9.0-33.8]) and 21 of 84 males sampled (25.0%; 95%CI=[15.7 34.3]). 60% (18 of 30; 95%CI=[42.5-77.5]) of seropositive samples were positive either for Phase I antigen or for both Phase I and II antigens, representing cases of chronic infection. Applying Spearman's rank correlation, the percentage of seropositive humans was significantly correlated with that observed for sheep (r=1.00; p<0.001), but not for cows (r=-0.5; p=0.667). CONCLUSIONS: The results obtained, although based on a small sample, suggest that the disease is present in the territory of Western Sicily, both in animals and in humans. A closer collaboration between doctors and veterinarians is therefore necessary to fight against the spread of the infection. PMID- 27007522 TI - Neospora caninum and Toxoplasma gondii antibodies in red foxes (Vulpes vulpes) in the Czech Republic. AB - INTRODUCTION AND OBJECTIVE: Neospora caninum and Toxoplasma gondii are worldwide spread parasites, causing serious illnesses in sensitive animals; toxoplasmosis is also important zoonosis. Although neosporosis is not considered as a zoonosis, it leads to aborted births in cattle, as well as paresis and paralysis in dogs. OBJECTIVE: The aim of this study was to discover the prevalence of N. caninum and T. gondii antibodies in red foxes (Vulpes vulpes) in the Czech Republic. MATERIALS AND METHOD: Sera of 80 foxes from 8 regions of the Czech Republic were tested for antibodies to N. caninum and T. gondii by competitive enzyme linked immunosorbent assay (cELISA) and indirect ELISA. All samples were simultaneously tested by indirect fluorescent antibody test (IFAT) to detect both N. caninum and T. gondii antibodies. RESULTS: Antibodies to N. caninum were found by IFAT in 3 (3.8%) red foxes with titre 50 and in 2 (2.5%) red foxes with inhibition 42.7% and 30.2 %. Antibodies to T. gondii were found in all tested animals in both IFAT (titres 50-6400) and in ELISA (S/P ranging from 34%-133%). CONCLUSION: This is the first prevalence study of N. caninum and T. gondii antibodies in red foxes in the Czech Republic. The results obtained show that red foxes are exposed at different levels to both protozoan infections, and thus could play an important role in the transmission cycle of N. caninum and T. gondii in sylvatic cycle. PMID- 27007524 TI - Time linkages between pollination onsets of different taxa in Perugia, Central Italy--an update. AB - INTRODUCTION AND OBJECTIVE: In the last decades, increasing attention has been paid to pollinosis. Numerous studies have been carried out concerning the pollination timing of allergenic plant species and the possibility to forecast its beginning and intensity using several statistical methods and models. This study proposes a simple and fast method to identify in advance the time lapse in which the pollination of some allergenic taxa should start. MATERIALS AND METHODS: The times of pollination of 14 taxa were recorded in the area of Perugia (Central Italy) by means of a 7-volumetric Hirst-Type pollen trap. For a 30-year period (1984-2013), annual starting dates were calculated for each taxa, using the 5% method (Lejoly-Gabriel). The time linkages between these starting dates were then estimated, considering them in pairs and calculating linear regression coefficients. RESULTS: For the significantly linked species, forecasting models were obtained by means of linear regression analysis. To apply these models to the ongoing pollen season, pollination beginning of the earlier species has to be calculated using a sum-based method. From this date, through the obtained equations, it is possible to predict the approximate period in which the pollination of the second linked taxa should start. CONCLUSIONS: The possibility to predict the start of the pollen season of these taxa could be of great importance from the allergological point of view. In fact, an early or delayed flowering can have considerable effects in the prophylaxis programming and efficacy. PMID- 27007523 TI - Serological and molecular evidence of Coxiella burnetii in samples from humans and animals in China. AB - INTRODUCTION: Coxiella burnetii is the agent of Q fever, a worldwide zoonosis. To add to the available knowledge of the disease in China, C. burnetti infections were investigated in convenience samples from five animal species and humans from Yangzhou, Jiangsu province, eastern China. MATERIALS AND METHODS: Commercial ELISA kits were used to detect antibodies to phase I and II C. burnetii. A FRET qPCR targeting the outer membrane protein com1 gene was also developed to detect C. burnetii DNA in blood samples from animals and humans, and bovine milk samples. RESULTS: Seropositive cattle (44/150; 29%), goats (33/150; 22%), humans (45/180; 25%) and pigs (4/130; 3%) were found, while dogs (0/136; 0%) and cats (0/140; 0%) were seronegative. Seropositivity in humans was associated with increasing age, but there was no gender difference. DNA was amplified from two milk samples (2/150, 1.3%), while none of the blood samples were positive. The sequences of the obtained amplicons were identical to those of the com1 gene of the universal C. burnetii RSA 493 strain and other stains from China. CONCLUSIONS: The findings indicaten that C. burnetii is endemic in Yangzhou, China, and therefore human and animal health workers should be aware of the possibility of infections and the occurrence of outbreaks of Q fever. PMID- 27007525 TI - 'TB or not TB?' Problems of differential diagnosis of cutaneous mycobacteriosis and tuberculosis--A Case Study and interdisciplinary discussion. AB - The diagnosis of cutaneous tuberculosis poses a serious challenge due to many skin diseases of different etiology resembling the lesions caused by the TB (tuberculosis) bacillus, and difficulties in confirming the disease. The presented case concerns skin lesions in a hobby aquarist stung in the finger of the left hand by a fish. The resulting inflammatory infiltration was to be cutaneous tuberculosis or mycobacteriosis caused by MOTT (Mycobacterium other than tuberculosis). Laboratory, pathomorphologic, genetic and microbiologic tests of samples obtained from the patient, fish and water in the aquarium gave ambiguous results. A multidisciplinary discussion is presented on the difficulties in the differential diagnosis, problems with a clear interpretation of the results of various conducted tests, and possible ways of transmission of the infection, relevant to the described example. PMID- 27007526 TI - Cytotoxicity induced by cypermethrin in Human Neuroblastoma Cell Line SH-SY5Y. AB - The purpose of this study was to evaluate the cytotoxic potential of Cypermethrin (CM) on cultured human Neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with CM at 0-200uM for 24, 48, and 72 h, in vitro. It was found that CM induced the cell death of Neuroblastoma cells in a dose- and time-dependent manner, as shown by LDH assays. Next, some aspects of the process of cell death triggered by CM in the human SH-SY5Y cell line were investigated. It was revealed that the pan caspase inhibitor Q-VD-OPh, sensitizes SH-SY5Y cells to necroptosis caused by CM. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 failed to attenuate the effect of the pesticide. Finally, it was shown that inhibition of TNF-a by Pomalidomide (PLD) caused statistically significant reduction in CM-induced cytotoxicity. Overall, the data obtained suggest that CM induces neurotoxicity in SH-SY5Y cells by necroptosis. PMID- 27007527 TI - Analysis of main T-cell subsets and activated T supressor/cytotoxic cells in patients with Borrelia burgdorferi s. lato only infection and co-infections with Anaplasma phagocytophilum, Bartonella spp. and Babesia microti. AB - INTRODUCTION: The study was designed to assess the role of some important immunologic factors with regards to both laboratory results and clinical symptoms in patients with confirmed Lyme disease. Additional examinations were carried out for co-infections with a number of tick-borne pathogens. MATERIAL AND METHODS: The study group consisted of 54 patients with Lyme disease and a group of 21 healthy controls. Serology of co-infections with Anaplasma phagocytophilum, Bartonella spp. and Babesia microti was carrieed out in all patients. Blood samples were stained using the whole-blood lysis method and analyzed concurrently on a flow cytometer FACSCalibur. Directly conjugated anti-human monoclonal antibodies against CD3, CD4, CD8, CD16, CD56, HLA-DR and CD69 were used. RESULTS: No significant differences were observed with respect to thepretreatment level of CD4+ and CD8+ cells. In patients with symptoms relief and symptoms persistence, lower percentages of CD4+ and CD8+ cells were found, but with no statistical dependence. In the study group, both in patients with and without co-infections, pretreatment values of CD16+CD56+ cells did not differ significantly. In patients who did not respond to the treatment, the baseline percentage of NK cells was higher (P<0.01) than in group with clinical improvement, and lower after the treatment, whereas in patients with symptoms relief after the treatment there was an increase in the percentage of NK cells. CONCLUSION: Co-infections with Anaplasma phagocytophilum, Bartonella spp. and Babesia microti had no impact on T cell percentages in Lyme disease patients. There was a lower baseline percentage of NK cells in patients not responding to antibiotic treatment. PMID- 27007528 TI - Differences in achieving treatment goals with statin use in various regions of Poland--3ST-POL study results. AB - INTRODUCTION AND OBJECTIVE: Dyslipidemia is the most common factor leading to ischemic heart disease, which is one of the leading causes of death. The use of statins is the most important preventative measure of ischemic heart disease; however, their efficacy in patients in Poland is still too low. The purpose of this study was to evaluate regional differences in achieving treatment goals in total cholesterol (TC) and LDL cholesterol levels in patients treated with statins on an outpatient basis. MATERIALS AND METHODS: A survey was used to evaluate efficacy of treatment, completed by 49,950 patients in Poland treated with statins in 2008. The territory of Poland was divided into 4 research regions: the Northeast (NE), Northwest (NW), Southeast (SE), and Southwest (SW) regions. RESULTS: The largest group of patients resided in the SW region, the smallest in the SE region. Participants of the study suffered from hypercholesterolemia, on average, for at least a year before completing the study survey. Effective treatment leading to achievement of target TC was observed in less than 10% of the patients. Rate of achievement of target cholesterol levels was highest in the NE region, lowest in the NW region. Cardiologists were more successful in achieving therapeutic goals than GPs. Similar correlations between regions and doctors' specializations were observed for LDL values. CONCLUSIONS: Significant differences in the efficacy of treatment with statins were observed among the study group and were evaluated based on achievement of target TC and LDL cholesterol levels. Better results achieved in the NE region may be because the region includes the Masovian province, which is the most economically developed region in Poland. PMID- 27007529 TI - Immune and clinical response to honeybee venom in beekeepers. AB - OBJECTIVE: The aim of the study was to assess immune response to honeybee venom in relation to the degree of exposure, time after a sting and clinical symptoms. MATERIALS AND METHOD: Fifty-four volunteers were divided into 2 groups: beekeepers and a control group. The serum levels of total IgE (tIgE), bee venom specific IgE (venom sIgE), phospholipase A2-specific IgE (phospholipase A2 sIgE), tryptase and venom-specific IgG4 (venom sIgG4) were determined. In beekeepers, diagnostic tests were performed within 3 hours following a sting and were repeated after a minimum of 6 weeks from the last sting. In individuals from the control group, the tests were performed only once, without a sting. RESULTS: The tests showed significant differences in venom sIgE (beekeepers' median = 0.34 kUA/l, control group median = 0.29 kUA/l), baseline serum tryptase (beekeepers' median = 4.25 ug/l, control group median = 2.74 ug/l) and sIgG4 (beekeepers' median = 21.2 mgA/l, control group median = 0.14 mgA/l), confirming higher levels of the tested substances in the beekeepers than in the control group. A significant positive correlation was observed between phospholipase A2 sIgE concentration and severity of clinical symptoms after a sting in the group of beekeepers. It was also demonstrated that the clinical symptoms after a sting became less severe with increasing age of the beekeepers. CONCLUSIONS: The differences in the immune response to a bee sting between the beekeepers and individuals not exposed to bees were probably due to the high exposure of the beekeepers to honeybee venom allergens. This may suggest a different approach to the bee venom allergy diagnostic tests in this occupational group. PMID- 27007530 TI - Clinical and health care aspects of respiratory tract disorders in Poland. AB - INTRODUCTION: Respiratory diseases constitute a public health priority worldwide. This is related to the increasing exposure to microorganisms, toxic factors, allergens, drugs and smoking, as the most important factors. Increasing costs of health promotion, prevention, diagnosis and treatment of respiratory tract diseases forces the search for effective strategies in the reduction of costs without making a significant impact of these activities on health results. Chronic obstructive pulmonary disease (COPD) is an example of these diseases with increasing incidence, which has few known modifiable factors and absorbs large medical and social costs. OBJECTIVES: The aim of this study is to present the conception of cost driver analysis that could be useful in constructing a good combination of the EBM-based treatment with cost reduction decisions. MATERIAL AND METHODS: Analysis of cost drivers was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and Polish recommendations of COPD diagnosis and treatment. The proposition of cost reduction strategy in COPD treatment was based on identification of cost drivers in value chain conception. RESULTS AND CONCLUSIONS: An increasing incidence and treatment costs of COPD force the search for methods of costs reduction in health care. Identifying, evaluating and modifying the cost drivers with use of the value chain conception could be an effective method in achieving these objectives. PMID- 27007531 TI - Prediction of biological sensors appearance with ARIMA models as a tool for Integrated Pest Management protocols. AB - INTRODUCTION AND OBJECTIVES: Powdery mildew caused by Uncinula necator and Downy mildew produced by Plasmopara viticola are the most common diseases in the North West Spain vineyards. Knowledge of airborne spore concentrations could be a useful tool in the Integrated Pest Management protocols in order to reduce the number of pesticide treatments, applied only when there is a real risk of infection. MATERIAL AND METHODS: The study was carried out in a vineyard of the D. O. Ribeiro, in the North-West Spain, during the grapevine active period 2004 2012. A Hirts-type volumetric spore-trap was used for the aerobiological monitoring. RESULTS: During the study period the annual total U. necator spores amount ranged from the 578 spores registered in 2007 to the 4,145 spores sampled during 2008. The highest annual total P. viticola spores quantity was observed in 2010 (1,548 spores) and the lowest in 2005 (210 spores). In order to forecast the concentration of fungal spores, ARIMA models were elaborated. CONCLUSIONS: The most accurate models were an ARIMA (3.1.3) for U. necator and (1.0.3) for P. viticola. The possibility to forecast the spore presence 72 hours in advance open an important horizon for optimizing the organization of the harvest processes in the vineyard. PMID- 27007532 TI - Environmental exposure to zinc and copper influences sperm quality in fertile males. AB - INTRODUCTION: The presented study was designed to investigate the associations between environmental exposure to zinc and copper and levels of the parameters of oxidative stress and antioxidant defence system and selected cytokines in the seminal plasma of fertile males. MATERIALS AND METHODS: The study population consisted of 65 fertile male volunteers from the southern region of Poland. Based on the medians of the levels of copper and zinc in seminal plasma, the study subjects were divided into 4 subgroups: groups with low and high environmental exposure to copper (Cu-L and Cu-H), groups with low and high environmental exposure to zinc (Zn-L and Zn-H). RESULTS: Semen volume, pH, count, motility and morphology of sperm cells in the Cu-L and Cu-H groups did not differ significantly. In the Cu-H group, TOS was increased significantly by 243% when compared to the Cu-L group. Similarly, median of IL-10 level in the Cu-H group was increased by 144% compared to the Cu-L group. Spearman correlation showed positive correlations between the levels of copper and TOS and IL-10. Negative correlations between copper and G-CSF and GM-CSF were also shown. In the Zn-L group, the percentage of progressively motile sperm cells after 1 hour was significantly higher by 17%, compared to the Zn-L group. In the Zn-H group, levels of G-CSF and MCP-1 were significantly higher by 70% and 145%, respectively, compared to the Zn-L group. The level of IL-10 was significantly lower in the Zn-H group by 60%, compared to the Zn-L group. Spearman correlation indicated that there is a positive correlation between the level of zinc and thiol groups, G-CSF and GM-CSF. Negative correlations between zinc and TOS and IL 10 were also shown. CONCLUSION: Zinc enhances motility in fertile men. This beneficial effect of zinc may be due to zinc-induced reduction in the plasma oxidative stress intensity and modulations of the immune response. This study confirms the antagonistic relationship between zinc and copper. PMID- 27007534 TI - The effects of caffeine administered at different temperatures on foetal development. AB - An easy access to products containing caffeine makes it widely consumed to excess by the general population, including pregnant women. Beverages containing caffeine are consumed at different temperatures (iced, hot, room temperature). Caffeine easily passes through biological membranes, including the blood-brain barrier, the placental barrier, and can also enter the amniotic fluid, breast milk and semen. The aim of this study was to evaluate the relationship between caffeine's developmental toxicity, and the solution's temperature (both low and high) administered to pregnant female rats. Fertilized females were randomly divided into two main groups: an experimental (E) and a control group (C). The experimental groups received caffeine (30mg/day) in 10 (E1), 25 (E2) and 45(o)C (E3). The females in the control group were given water at the same temperature (C1, C2 and C3). On the day 21 of pregnancy, the pregnant females were killed by decapitation, using a specially prepared laboratory guillotine, after which the mothers' internal organs were weighed. Additionally, the offspring were examined using standard teratological methods. The study found that caffeine administered to pregnant females at a dose of 30mg/day and at the temperatures of 10 degrees C, 25 degrees C or 45 degrees C did not produce any teratogenic effects. The only sign of its adverse effect was the appearance of developmental abnormalities in the form of haematomas and saturated bleeding in the internal organs. These changes most frequently occurred in foetuses of females which received caffeine at 10 degrees C or 45 degrees C. PMID- 27007533 TI - Impact of beliefs about pain control on perceptions of illness in surgical patients. AB - OBJECTIVES: Adequacy of pain management in surgical patients is a major contributor to overall treatment outcomes and positive illness perceptions. However, it may be subjectively predetermined by a patient's beliefs about pain control. This study assesses the relationships between beliefs about pain control and perceptions of illness in thoracic surgical patients. MATERIALS AND METHOD: A total of 135 patients (72 women and 63 men; mean age 58.4+/-14.25y) were enrolled in the questionnaire study based on the Beliefs about Pain Control Questionnaire (BPCQ) by S. Skevington and the Multidimensional Essence of Disease and Illness Scale (MEDIS) by J. Sak. Analyses were conducted with use of the k-means clustering technique and one-way ANOVA. RESULTS: Applied classification revealed 3 different clusters of patients with regard to their beliefs about pain control: 1) weak, undifferentiated pain control; 2) intensified influence of chance pain control; 3) strong undifferentiated pain control. Significant differences in illness perceptions between clusters were disclosed in 3 MEDIS dimensions: self realization constraints (F=4.70; p=0.01; 1 vs. 3), mental dysfunction (F=3.44, p=0.04; 1 vs. 3) and physical dysfunction (F=3.10, p=0.05; 1 vs 2). Patients in cluster 3 demonstrated a greater feeling of self-realization constraints and mental dysfunction than in cluster 1, whereas patients in cluster 2 perceived physical dysfunction as a greater distress than those in cluster 1. CONCLUSIONS: Beliefs about pain control significantly influence illness perceptions, and thus may affect the results of treatment in surgical patients. Psychological modelling of beliefs about pain control may offer a valuable way to improve overall clinical outcomes. PMID- 27007535 TI - Selected non-somatic risk factors for pregnancy loss in patients with abnormal early pregnancy. AB - INTRODUCTION AND OBJECTIVE: Spontaneous abortion constitutes one of the most frequent complication of human pregnancy. Despite intensive research efforts undertaken to date, the etiopathogenesis of early pregnancy loss has not been fully elucidated. The objective of this study was to analyze the role of selected non-somatic risk factors for early pregnancy loss in patients with various clinical manifestations of spontaneous abortion. MATERIALS AND METHODS: The study included 242 women hospitalized between 2001 and 2004 in the 3rd Chair and Department of Gynecology, Medical University of Lublin, Poland (Teaching Hospital No.4) with various clinical categories of spontaneous abortion. Each patient completed a questionnaire assessing her exposure to the examined factors. In patients with threatened abortion dismissed from the hospital with viable gestation, the course of pregnancy was followed-up using questionnaire data and medical records. RESULTS: In the studied population of women with abnormal early pregnancy course, a significant impact on the risk of miscarriage was observed in case of such factors as: exposure to stress at home and limited number of hours of nightly sleep. Factors such as occupational hazards, diet, stress, heavy housework and use of cigarettes or alcohol did not exert a significant effect on the risk of miscarriage in the studied population. CONCLUSIONS: The results of this study confirm the complexity of the early pregnancy loss etiopatogenesis. Further research need to be conducted in order to identify the non-somatic causative agents of various clinical forms of miscarriage. It may help do select women in reproductive age at high risk of early pregnancy loss and show the ways in which effective preventive measures can be introduced in such population. PMID- 27007536 TI - Opinions and attitudes of parturients, midwives, and obstetricians about Caesarean section in the provinces of Podkarpackie, Poland, and Ivano-Frankivsk, Ukraine. AB - INTRODUCTION AND OBJECTIVE: Present the opinions of parturients, midwives, and obstetricians concerning CS in the provinces of Podkarpackie (Poland) and Ivano Frankivsk (Ukraine). MATERIAL AND METHODS: An anonymous questionnaire for parturients (n=1,295), midwives (n=47) and obstetricians (n=78), assessing demographics, knowledge and attitudes concerning CS, was distributed in 13 hospitals. In addition to measured anxiety among parturients, we also used the State-Trait Anxiety Inventory (STAI). RESULTS: Differences between the subgroups concerned respondents' ages and place of residence (p=0.0000). Parturients from Poland more often accepted the possibility of vaginal delivery after previous CS (p=0.0000), they more often believed that free access to epidural analgesia and the presence of a chosen partner in the delivery room would decrease the CS rate (p=0.0000). Polish midwives more rarely accept the idea of CS on maternal request (p=0.0012) and were convinced that free access to epidural analgesia could decrease the rate of CS (p=0.0479). In Poland parturients more often accepted CS on maternal request than obstetricians and midwives (p=0.0000). In Ukrainian population midwives and obstetricians more often accepted possibility of natural delivery after previous CS (p=0.0010). According connected with delivery in Poland parturients returned lower scores on the A-State scale (p=0.0000), but higher scores on the A-Trait scale (p=0.0067). CONCLUSIONS: There are some differences in Polish and Ukrainian obstetricians, midwives and parturients in respect of: - vaginal delivery after CS, - epidural analgesia, - CS on request, - anxiety connected with labour. The above may to some extend explain the difference in Cs rate in two countries. PMID- 27007537 TI - Next generation sequencing for preimplantation genetic testing of blastocysts aneuploidies in women of different ages. AB - Most of the current preimplantation genetic screening of aneuploidies tests are based on the low quality and low density comparative genomic hybridization arrays. The results are based on fewer than 2,700 probes. Our main outcome was the association of aneuploidy rates and the women's age. Between August-December 2013, 198 blastocysts from women (mean age 36.3+-4.6) undergoing in vitro fertilization underwent routine trophectoderm biopsy. NGS was performed on Ion Torrent PGM (Life Technologies). The results were analyzed in five age groups (<31, 31-35, 36-38, 39-40 and >40). 85 blastocysts were normal according to NGS results. The results in the investigated groups were (% of normal blastocyst in each group): <31 (41.9%), 31-35 (47.6%), 36-38 (47.8%), 39-40 (37.7%) and >40 (38.5%). Our study suggests that NGS PGD is applicable for routine preimplantation genetic testing. It allows also for easy customization of the procedure for each individual patient making personalized diagnostics a reality. PMID- 27007538 TI - Health beliefs and sense of one's own efficacy and prophylaxis of osteoporosis in peri- and post-menopausal women. AB - INTRODUCTION AND OBJECTIVE: Osteoporosis constitutes one of the relevant health, social and economic problems of the contemporary world which concerns 200 million women, of whom about 20-25% will experience a bone fracture. The aim of the study was to learn about the health beliefs and sense of self-efficacy in peri- and post-menopausal women regarding the prevention of osteoporosis. MATERIALS AND METHOD: A group of 300 randomly chosen women aged 45-65 who were patients of healthcare centres in Chelm, Lublin, and the surroundings of Zamosc (eastern Poland), was examined. Own Health Beliefs Scale (OHBS) associated with Osteoporosis and Own Efficacy Evaluation Scale (OSES) were used for the study. The obtained material was subjected to descriptive and statistical analysis. Tukey test, t-student test and variance analysis (ANOVA) were all applied. A P value less than 0.05 was considered statistically significant. Results were analysed using the SPSS version 19 software package. RESULTS AND CONCLUSIONS: It was stated that respondents had thought that osteoporosis is an averagely serious health problem, and they did not feel peculiarly exposed to falling ill with the disease. They attached great significance to the benefits of physical activity and correct nutrition. The perception of barriers to calcium intake and everyday exercise was moderate. Health motivation remained at the average level. Socio demographic conditions influenced the respondents' health beliefs in a statistically significant way. Sense of self-efficacy from the aspect of taking possible action preventing osteoporosis remained on the average level; in addition, respondents more often declared the desire for a change in eating habits than resorting to physical activity. PMID- 27007539 TI - Comparison of selected sperm parameters between 6,278 males in Poland and Ukraine. AB - The phenomenon of deterioration of the quality of sperm in Poland and Ukraine has not been unequivocally evidenced by scientific research. Spermiogramms of males reporting for the first time to infertility treatment centres in both countries were examined, and trends in changes of selected sperm parameters analyzed during the period of study. Analyses covered the spermiograms of 6,278 men living in the examined regions for at least 3 years. It was found that mean sperm concentration of patients in the Lublin and the Lvov regions did not differ, but the total mean number of spermatozoa produced by Poles was higher than in Ukrainians. The quality of semen with respect to motility and sperm morphology was better in Ukrainian than Polish patients. Despite differences concerning concentration, the amount of sperm produced and percentage of spermatozoa showing progressive motility which occurred between individual years, no clear tendency was observed towards change of these parameters in a specified direction in both countries during the years examined. Among men examined in the Lublin Region, a tendency was noted towards decrease in the percentage of morphologically normal spermatozoa in the ejaculate, while among patients from the Lvov Region an opposite tendency was observed. PMID- 27007540 TI - Augmentative and Alternative Communication (AAC) for a patient with a nonfluent/agrammatic variant of PPA in the mutism stage. AB - INTRODUCTION: The paper presents an example of the successful administration of the Augmentative and Alternative Communication (AAC) system. Such an approach is of particular significance in cases of patients with speech and language deterioration, which is observed in a nonfluent/agrammatic variant of primary progressive aphasia (PPA-G). Regaining the ability to communicate with others proves to be very important for the patients' self-esteem and enables them to restore previously broken social bonds. CASE HISTORY: The patient A.G., aged 73, a right-handed woman, had been a teacher of Polish before suffering from speech disorders of the PPA-G type. As the disease progressed, her communication deteriorated and finally she developed mutism. The patient was given a clinical and imaging-supported diagnosis of an isolated nonfluent/ agrammatic variant of primary progressive aphasia (PPA-G). The Augmentative and Alternative Communication (AAC) system specially designed for her needs was introduced to help the patient to regain the possibility to communicate. After 20 sessions of training with the use of simple equipment she was again able to communicate non verbally with her son and with the staff of the nursing home. At the same time, a considerable improvements in her social functioning, including daily activities, was observed. CONCLUSIONS: Loss of the ability to communicate with others has a serious impact upon a patient's quality of life, and often results in withdrawal and an inability to lead an independent life. The introduction of the Augmentative and Alternative Communication (AAC) system proves to be a great help, not only for regaining the ability to communicate, but also for the restoration of social bonds. In consequence, the previously mute patient begins to show signs of social cooperation. PMID- 27007541 TI - Homocysteine, antioxidant vitamins and lipids as biomarkers of neurodegeneration in Alzheimer's disease versus non-Alzheimer's dementia. AB - INTRODUCTION AND OBJECTIVE: Evidence for the benefit of antioxidants' based therapeutic intervention in dementia are inconsistent. Parallel studies in disease forms of dementia different than Alzheimer's are even less conclusive. In this study, the role of serum levels of homocysteine (tHcy), lipids and antioxidants in predicting the risk of cognitive decline in Alzheimer's disease (AD) versus non-Alzheimer's dementias (n-AD). The objective was to add to the ongoing cumulative research to establish the biochemical baseline for potential nutri-therapeutic intervention in different forms of dementia. MATERIALS AND METHOD: 65 participants with dementia (DP-s) were divided into two groups: ADP- patients with Alzheimer's disease and n-ADP--patients with dementia of a different etiology than primary neurodegenerative dementia in the course of Alzheimer's disease. Cognitive function was assessed by Mini-Mental State Examination (MMSE) and related to plasma levels of tHcy, folate, vitamins B-6, B 12, lipids and vitamins A and E for both groups. Also examined were associations between cognitive impairment and several variables (age, education, duration of dementia) that might confound nutrition-cognition associations. RESULTS: A significant reduction in serum vitamin A levels and elevation of total cholesterol levels were shown for the DP-s group compared to those in the control group. Moreover, significant differences were found in MMSE data and serum vitamin E and tHcy levels between patients with ADP and n-ADP. The scores for MMSE showed a correlation with the vitamin E levels and duration of dementia in the ADP group and/or correlation with tHcy, levels of vitamins A and/or E, and duration of dementia in the n-ADP group. CONCLUSIONS: The results obtained suggest that elevated serum tHcy and decreased levels of vitamins A and E are associated with an increased risk of non-Alzheimer's dementias, although further studies involving a larger cohort are now needed to verify these results. PMID- 27007542 TI - Relationships between personality traits, resting serum hormones and visuomotor ability in male judokas. AB - INTRODUCTION: The purpose of this research was to study the relationships between selected personality features, the speed and accuracy of visumotor ability and hormonal status in the blood of male judokas. MATERIALS AND METHOD: Forty-five male judokas whose body mass ranged from 66-100 kg were included in the study. Each one was examined once during a single annual competitive season lasting from March-October. The protocol of the study comprised five procedures carried out in the following order: (a) capillary blood sampling in the morning (07:30), (b) second capillary blood sampling directly prior to the personality examination, (c) examination of the personality traits, (d) testing of visuo-motor ability with the use of an electronic cross-shape electronic device, (e) third capillary blood sampling after the entire study. The entire study started and ended in the morning. For each subject, the three serum samples were pooled and the levels of cortisol (C) and testosterone (T) were determined in the serum specimen. RESULTS: There were significant correlations among the scores in selected personality traits, anxiety (A), neuroticism (N), extraversion (E), perseveration (P), emotional reactivity (ER) and achievement motivation (AM). The C level did not correlate with any variables, however, it did positively correlate with E and visuo-motor ability. There were inverse relationships between E and A, N, P and ER. CONCLUSIONS: The study confirmed relationships in the androgenic status in circulation, personality traits and psycho-motor abilities. PMID- 27007543 TI - Deep brain stimulation for aggressive behavior and obsessive-compulsive disorder. AB - Drug-resistant obsessive-compulsive disorder and aggressive behavior are two severely disabling psychiatric conditions which may carry a certain burden on the patients themselves and on their families. In the last decade, the fields of interests of deep brain stimulation (DBS) also encompass psychiatric disorders, supported by imaging and neurophysiological techniques. We here report our institutional experience with the two above-mentioned disorders, describing the procedure commonly employed and the results obtained. Refinement of such techniques, possibly relying on advanced magnetic resonance imaging (MRI), together with probabilistic pictures of field of activation models, could shed more light into this complex field of investigation; further studies are necessary to confirm and make actual results a starting point to new and more precise methodologies in this stimulating research field. PMID- 27007545 TI - Key role of magnetic resonance imaging in the diagnosis of infections around the hip and pelvic girdle mimicking septic arthritis of the hip in children. AB - Infections around the hip and the pelvic girdle mimicking septic hip arthritis are rare conditions in the pediatric population requiring urgent treatment. They are not readily diagnosed because of rarity, resemblance to septic hip, and unclear pathophysiology, which often results in misdiagnosis, delayed diagnosis, and delayed treatment. The aim of this study was to prove the key role of magnetic resonance imaging (MRI) as the first-line modality in making a early definite diagnosis of an uncommon perihip infection in children. We retrospectively reviewed 20 children with a provisional diagnosis of unilateral septic hip who were confirmed finally to have perihip infections and combined with concomitant osteomyeltis using MRI. All patients were treated with intravenous antibiotics with or without abscess aspiration until normalization of clinical symptoms and laboratory tests including serum C-reactive protein and erythrocyte sedimentation rate. All infections healed successfully and the final C-reactive protein was recovered to a mean of 0.37 mg/dl (range 0.01-0.78 mg/dl) without recurrence or complication. Although the MRI is costly and limited in practical application, it was found to be effective as a primary diagnostic tool for an early, accurate diagnosis of infections around the hip and the pelvic girdle in children to correctly guide the decision and the approach for treatment. PMID- 27007544 TI - The Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of the Bauhinia Championii Flavone are Connected with Protection Against Myocardial Ischemia/Reperfusion Injury. AB - BACKGROUND/AIMS: Previous studies have demonstrated that Bauhinia championii flavone (BCF) exhibits anti-oxidative, anti-hypoxic and anti-stress properties. This study was designed to investigate whether BCF has a cardioprotective effect against myocardial ischemia/reperfusion (I/R) injuries in rats and to shed light on its possible mechanism. METHODS: The model of I/R was established by ligating the left anterior descending coronary artery for 30 min, then reperfusing for 180 min. Hemodynamic changes were continuously monitored. The content of malondialdehyde (MDA) as well as the lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. The release of interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis of cardiomyocytes was determined by caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of TLR4, NF-x03BA;Bp65, Bcl-2 and Bax were detected by western blotting. RESULTS: Pretreatment with BCF significantly reduced the serum levels of LDH, MDA and IL-6, but increased the activities of SOD and GSH-Px. It also attenuated myocardial infarct size, reduced the apoptosis rate and preserved cardiac function. Furthermore, BCF inhibited caspase-3 activity and the expression of TLR4, phosphorylated NF-x03BA;Bp65 and Bax, but enhanced the expression of Bcl-2. CONCLUSION: These results provide substantial evidence that BCF exerts a protective effect on myocardial I/R injury, which may be attributed to attenuating lipid peroxidation, the inflammatory response and apoptosis. PMID- 27007546 TI - Effect of growing rod on sagittal and spinopelvic parameters in early-onset scoliosis patients. AB - Growing rod is a commonly used surgery for early-onset scoliosis (EOS). However, the effect of growing-rod lengthening on the spinopelvic alignment is unclear. In this study, 21 EOS patients treated by growing rod were evaluated retrospectively and thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI) , sacral slope (SS), pelvic tilt (PT), and sagittal vertical axis (SVA) were measured. Preoperatively, the mean TK, LL, PI, PT, SS, and SVA were 27.4 degrees , 35.2 degrees , 43.8 degrees , 7.5 degrees , 33.8 degrees , and 47.7 mm respectively. After the last lengthening, TK, LL, PI, PT, SS, and SVA were 28.3 degrees , 28.06 degrees , 41.4 degrees , 7 degrees , 5.2 degrees , and 42.6 mm, respectively. The sagittal plane parameters in our EOS patients were not significantly altered during the lengthening period. PMID- 27007547 TI - Healthy Preterm Newborns Show an Increased Frequency of CD4(+) CD25(high) CD127(low) FOXP3(+) Regulatory T Cells with a Naive Phenotype and High Expression of Gut-Homing Receptors. AB - Treg cells are crucial to prevent immune dysregulation, but little is known about the frequency of these cells in neonates, particularly in very/moderate and late preterm newborns studied as separate groups. The CD4(+) CD25(hi) CD127(lo) FOXP3(+) Treg population was phenotypically characterized to assess maturation markers and gut-homing integrins by flow cytometry in the cord blood of healthy preterm newborns born at 30-33(6/7) gestation weeks (Group 1), at 34-36(6/7) gestation weeks (Group 2) and term newborns born at 37-41 gestation weeks (Group 3), compared to healthy adults. An inverse correlation of the Treg percentage and gestational age was found, with significantly higher frequencies in Group 1 compared to Groups 2 and 3 and in Group 2 compared to Group 3, and significantly higher Treg frequencies and numbers in the neonates compared to the adults. All of the newborns exhibited increased Treg frequencies with a naive phenotype compared to adults. Cytotoxic T-lymphocyte-associated protein 4 CTLA-4 expression in the naive Treg was decreased in both preterm groups compared with those from term newborns and adults, and in the memory Treg from Group 1 compared with the other groups. The frequencies of Treg expressing alpha4beta7 and alpha4beta1 integrins were higher in both preterm groups, but significantly different only in Group 1, when compared with those from the term newborns and the adults. In conclusion, although a high frequency of Treg is present in newborns, an immature phenotype with a higher expression of CD45RA and alpha4beta7/alpha4beta1 and a lower expression of CTLA-4 is found, particularly in the very preterm group. PMID- 27007548 TI - Selected Schizosaccharomyces pombe Strains Have Characteristics That Are Beneficial for Winemaking. AB - At present, wine is generally produced using Saccharomyces yeast followed by Oenococus bacteria to complete malolactic fermentation. This method has some unsolved problems, such as the management of highly acidic musts and the production of potentially toxic products including biogenic amines and ethyl carbamate. Here we explore the potential of the fission yeast Schizosaccharomyces pombe to solve these problems. We characterise an extensive worldwide collection of S. pombe strains according to classic biochemical parameters of oenological interest. We identify three genetically different S. pombe strains that appear suitable for winemaking. These strains compare favourably to standard Saccharomyces cerevisiae winemaking strains, in that they perform effective malic acid deacidification and significantly reduce levels of biogenic amines and ethyl carbamate precursors without the need for any secondary bacterial malolactic fermentation. These findings indicate that the use of certain S. pombe strains could be advantageous for winemaking in regions where malic acid is problematic, and these strains also show superior performance with respect to food safety. PMID- 27007549 TI - Left atrial volume and function in patients with white-coat hypertension assessed by real-time three-dimensional echocardiography. AB - BACKGROUND: White-coat hypertension (WCH) is a disease based on the disparity of a patient's blood pressure measurements between the physician's office and the patient's home environment. The aim of the present study is to evaluate the left atrial (LA) volume and functions in WCH. METHODS: In total, this study included 37 WCH (17 women, 20 men, mean age 48.4+/-5.7 years) and 30 healthy individuals (18 women, 20 men, mean age 47.9+/-7.5 years). All patients underwent real-time three-dimensional and comprehensive two-dimensional echocardiography (2DE) with tissue Doppler evaluation to estimate left atrial volumes and mechanical functions. RESULTS: LA diameters were significantly higher in the patients compared with the controls (37+/-2.8 vs. 35+/-3.1 mm, P=0.017). LA total systolic volume and LA maximal volume were significantly higher in the patients. (41.1+/ 6.9 vs. 35.5+/-3.7 ml, P<0.001; 25.8+/-5.4 vs. 21.3+/-3.3 ml, P<0.001, respectively). LA volume before LA contraction and LA active stroke volume were significantly higher in the patients with WCH than in the normotensives (24.4+/ 6.3 vs. 20.9+/-2 ml, P=0.002; 9.1+/-4.8 vs. 6.7+/-2.5 ml, P=0.007, respectively). Moreover, the LA expansion index was significantly higher in the patients with WCH than in the normotensives (178.7+/-53.6 vs. 155.3+/-36.3, P=0.037). However, the total emptying volume fraction of the LA was similar between the two groups. CONCLUSION: We showed that LA structural functions and volumes were increased in the WCH group. Although increased LA volume has been observed in many diseases, structural changes in LA may be accepted as an early sign for clinical cardiac remodeling in patients with WCH, suggesting the necessity of early intervention for preventing clinical cardiovascular disease. PMID- 27007550 TI - Efficacy and Safety of APO866 in Patients With Refractory or Relapsed Cutaneous T Cell Lymphoma: A Phase 2 Clinical Trial. PMID- 27007551 TI - In vitro sensitivity to methyl-prednisolone is associated with clinical response in pediatric idiopathic nephrotic syndrome. AB - The aim of this study was to evaluate the in vitro steroid sensitivity as a predictor of clinical response to glucocorticoids in childhood idiopathic nephrotic syndrome (INS). Seventy-four patients (median age 4.33, interquartile range [IQR] 2.82-7.23; 63.5% male) were enrolled in a prospective multicenter study: in vitro steroid inhibition of patients' peripheral blood mononuclear cell proliferation was evaluated by [methyl-(3) H] thymidine incorporation assay at disease onset (T0) and after 4 weeks (T4) of treatment. Steroid dependence was associated with increased in vitro sensitivity at T4 assessed both as drug concentration inducing 50% of inhibition (IC50 ; odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.24-0.85; P = 0.0094) and maximum inhibition at the highest drug concentration (Imax ; OR = 1.13, 95% CI = 1.02-1.31; P = 0.017). IC50 > 4.4 nM and Imax < 92% at T4 were good predictors for optimal clinical response. These results suggest that this test may be useful for predicting the response to glucocorticoid therapy in pediatric INS. PMID- 27007552 TI - New Dietary Guidelines Place Added Sugars in the Crosshairs. PMID- 27007553 TI - [Viral epidemic outbreaks and public health alerts studied at the National Centre of Microbiology during a two-year period (2012-2013]. PMID- 27007555 TI - The microphysics of collisionless shock waves. AB - Collisionless shocks, that is shocks mediated by electromagnetic processes, are customary in space physics and in astrophysics. They are to be found in a great variety of objects and environments: magnetospheric and heliospheric shocks, supernova remnants, pulsar winds and their nebulae, active galactic nuclei, gamma ray bursts and clusters of galaxies shock waves. Collisionless shock microphysics enters at different stages of shock formation, shock dynamics and particle energization and/or acceleration. It turns out that the shock phenomenon is a multi-scale non-linear problem in time and space. It is complexified by the impact due to high-energy cosmic rays in astrophysical environments. This review adresses the physics of shock formation, shock dynamics and particle acceleration based on a close examination of available multi-wavelength or in situ observations, analytical and numerical developments. A particular emphasis is made on the different instabilities triggered during the shock formation and in association with particle acceleration processes with regards to the properties of the background upstream medium. It appears that among the most important parameters the background magnetic field through the magnetization and its obliquity is the dominant one. The shock velocity that can reach relativistic speeds has also a strong impact over the development of the micro-instabilities and the fate of particle acceleration. Recent developments of laboratory shock experiments has started to bring some new insights in the physics of space plasma and astrophysical shock waves. A special section is dedicated to new laser plasma experiments probing shock physics. PMID- 27007554 TI - Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder. AB - Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual's fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0-11 years) and late (12-18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = 7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis. PMID- 27007556 TI - AMINOGLYCOSIDE RESISTANCE GENES IN Pseudomonas aeruginosa ISOLATES FROM CUMANA, VENEZUELA. AB - The enzymatic modification of aminoglycosides by aminoglycoside acetyltransferases (AAC), aminoglycoside-adenyltransferases (AAD), and aminoglycoside-phosphotransferases (APH), is the most common resistance mechanism in P. aeruginosa and these enzymes can be coded on mobile genetic elements that contribute to their dispersion. One hundred and thirty seven P. aeruginosa isolates from the University Hospital, Cumana, Venezuela (HUAPA) were evaluated. Antimicrobial susceptibility was determined by the disk diffusion method and theaac, aadB and aph genes were detected by PCR. Most of the P. aeruginosa isolates (33/137) were identified from the Intensive Care Unit (ICU), mainly from discharges (96/137). The frequency of resistant P. aeruginosaisolates was found to be higher for the aminoglycosides tobramycin and amikacin (30.7 and 29.9%, respectively). Phenotype VI, resistant to these antibiotics, was the most frequent (14/49), followed by phenotype I, resistant to all the aminoglycosides tested (12/49). The aac(6')-Ib,aphA1 and aadB genes were the most frequently detected, and the simultaneous presence of several resistance genes in the same isolate was demonstrated. Aminoglycoside resistance in isolates ofP. aeruginosa at the HUAPA is partly due to the presence of the aac(6')-Ib, aphA1 andaadB genes, but the high rates of antimicrobial resistance suggest the existence of several mechanisms acting together. This is the first report of aminoglycoside resistance genes in Venezuela and one of the few in Latin America. PMID- 27007558 TI - EPIDEMIOLOGY OF SCORPION ENVENOMATION IN THE STATE OF CEARA, NORTHEASTERN BRAZIL. AB - This report is a retrospective study of the epidemiology of scorpion sting cases recorded from 2007 to 2013 in the State of Ceara, Northeastern Brazil. Data were collected from the Injury Notification Information System database of the Health Department of Ceara. A total of 11,134 cases were studied and distributed across all the months of the studied period and they occurred mainly in urban areas. Victims were predominantly 20-29 years-old women. Most victims were bitten on the hand; and received medical assistance within 1-3 hours after being bitten. Cases were mostly classified as mild and progressed to cure. Scorpion envenomation in Ceara is an environmental public health problem that needs to be monitored and controlled throughout the year. PMID- 27007557 TI - SIXTEEN YEARS OF DERMATOMYCOSIS CAUSED BY Candida spp. IN THE METROPOLITAN AREA OF PORTO ALEGRE, SOUTHERN BRAZIL. AB - The yeasts of the genus Candida infect skin, nails, and mucous membranes of the gastrointestinal and the genitourinary tract. The aim of this study was to determine the prevalence of dermatomycoses caused by Candida spp., and their etiological aspects in the metropolitan area of Porto Alegre, Brazil. A retrospective study with data obtained from tertiary hospital patients, from 1996 to 2011, was performed. The analyzed parameters were date, age, gender, ethnicity, anatomical region of lesions, and the direct examination results. For all the statistical analyses, a = 0.05 was considered. Among positive results in the direct mycological examination, 12.5% of the total of 4,815 cases were positive for Candida spp. The angular coefficient (B) was -0.7%/ year, showing a decrease over the years. The genus Candida was more prevalent in women (15.9% of women versus 5.84% of men), and in addition, women were older than men (54 versus 47 years old, respectively). There was no difference between ethnic groups. The nails were more affected than the skin, with 80.37% of the infections in the nails (72.9% in fingernails and 7.47% in toenails). Our study corroborates the literature regarding the preference for gender, age, and place of injury. Moreover, we found a decrease in infection over the studied period. PMID- 27007559 TI - MOLECULAR SURVEILLANCE OF Plasmodium vivax AND Plasmodium falciparum DHFR MUTATIONS IN ISOLATES FROM SOUTHERN IRAN. AB - In Iran, both Plasmodium vivax and P. falciparum malaria have been detected, but P. vivax is the predominant species. Point mutations in dihydrofolate reductase (dhfr) gene in both Plasmodia are the major mechanisms of pyrimethamine resistance. From April 2007 to June 2009, a total of 134 blood samples in two endemic areas of southern Iran were collected from patients infected with P. vivax and P. falciparum. The isolates were analyzed for P. vivax dihydrofolate reductase (pvdhfr) and P. falciparum dihydrofolate reductase (pfdhfr) point mutations using various PCR-based methods. The majority of the isolates (72.9%) had wild type amino acids at five codons of pvdhfr. Amongst mutant isolates, the most common pvdhfr alleles were double mutant in 58 and 117 amino acids (58R 117N). Triple mutation in 57, 58, and 117 amino acids (57L/58R/117N) was identified for the first time in the pvdhfr gene of Iranian P. vivax isolates. All the P. falciparumsamples analyzed (n = 16) possessed a double mutant pfdhfrallele (59R/108N) and retained a wild-type mutation at position 51. This may be attributed to the fact that the falciparum malaria patients were treated using sulfadoxine-pyrimethamine (SP) in Iran. The presence of mutant haplotypes in P. vivax is worrying, but has not yet reached an alarming threshold regarding drugs such as SP. The results of this study reinforce the importance of performing a molecular surveillance by means of a continuous chemoresistance assessment. PMID- 27007560 TI - FACTORS RELATED TO ORAL CANDIDIASIS IN ELDERLY USERS AND NON-USERS OF REMOVABLE DENTAL PROSTHESES. AB - This study examined the association between oral candidiasis in elderly users and nonusers of prosthesis and its predisposing factors. To this end, we performed a cross-sectional study where saliva samples from 48 patients were collected they used prosthesis and 43 patients (control group) who did not use. Among the 91 patients, Candida spp were isolated in 40 (83.3%) who used prosthesis and in 23 (53.5%) in the control group. A statistically significant association was determined between the two groups, the isolation of yeasts and dental prosthesis (p < 0.05, OR = 4.3). The most common etiological agent was Candida albicans (37 isolates), with 23 (62.2%) in the denture group and 14 (37.8%) (control group). Among patients who presented clinical manifestations of oral candidiasis (n = 24), 83.3% (n = 20) belonged to the group that wore dentures, while only 16.7% (n = 4) belonged to the control group. Elderly patients with diabetes had 4.4 times higher estimated risk of developing oral candidiasis when compared with individuals without this condition. There was no statistically significant association between being user prostheses and have diabetes with the onset of candidiasis. No statistically significant association was determined between xerostomia, use of prosthesis and oral candidiasis. The use of prosthetics and poor oral hygiene in elderly patients predisposes to the development of oral candidiasis. PMID- 27007561 TI - ANTIFUNGAL POTENTIAL OF PLANT SPECIES FROM BRAZILIAN CAATINGA AGAINST DERMATOPHYTES. AB - Trichophyton rubrum and Trichophyton mentagrophytes complex, or Trichophyton spp. are the main etiologic agents of dermatophytosis, whose treatment is limited by the high cost of antifungal treatments, their various side effects, and the emergence of resistance amongst these species. This study evaluated the in vitro antidermatophytic activity of 23 crude extracts from nine plant species of semiarid vegetation (caatinga) found in Brazil. The extracts were tested at concentrations ranging from 1.95 to 1,000.0 mg/mL by broth microdilution assay against the reference strains T. rubrum ATCC 28189 and T. mentagrophytes ATCC 11481, and 33 clinical isolates of dermatophytes. All plants showed a fungicidal effect against both fungal species, with MIC/MFC values of the active extracts ranging from 15.6 to 250.0 ug/mL. Selected extracts of Eugenia uniflora (AcE), Libidibia ferrea (AE), and Persea americana (AcE) also exhibited a fungicidal effect against all clinical isolates of T. rubrum and T. mentagrophytes complex. This is the first report of the antifungal activity of Schinus terebinthifolius, Piptadenia colubrina, Parapiptadenia rigida, Mimosa ophthalmocentra, and Persea americana against both dermatophyte species. PMID- 27007562 TI - SEROVARS AND ANTIMICROBIAL RESISTANCE OF Salmonella spp. ISOLATED FROM TURKEY AND BROILER CARCASSES IN SOUTHERN BRAZIL BETWEEN 2004 AND 2006. AB - Salmonella spp. causes diseases in fowls, when species-specific serovars (Salmonella Pullorum and S.Gallinarum) are present in flocks, and public health problems, when non-typhoid serovars are isolated, as well as possible bacterial resistance induced by the preventive and therapeutic use of antimicrobials in animal production. This study describes the serovars and bacterial resistance of 280 Salmonella spp. strains isolated from turkey and broiler carcasses in Southern Brazil between 2004 and 2006. Salmonella Enteritidis was the most prevalent serovar (55.7%), followed by Heidelberg (5.0%), Agona (4.3%), Bredeney (3.9%), Hadar (3.2%), and Typhimurium (2.9%). Tennessee and S. Enterica subspecies enterica(O: 4.5) were isolated only in turkeys, and Hadar (18.6%) was the most prevalent serovar in this species. Antimicrobial susceptibility tests were performed in 178 isolates (43 from turkeys and 135 from broilers). All isolates were sensitive to amoxicillin + clavulanic acid, polymyxin B, ciprofloxacin, and norfloxacin, and were resistant to bacitracin and penicillin. Broiler carcass isolates showed resistance to nalidixic acid (48.9%), nitrofurantoin (34.3%), neomycin (9.6%), tetracycline (5.2%), and kanamycin (8.9%); and turkey carcass isolates were resistant to nalidixic acid (62.8%), tetracycline (34.9%), and neomycin (30.2%), with a significant difference in turkeys when compared to broiler carcass isolates. These results indicate the need for judicious use of antimicrobials in livestock production, given that the serovars identified are potential causes of food poisoning. PMID- 27007563 TI - AMERICAN CUTANEOUS LEISHMANIASIS WITH UNUSUAL CLINICAL PRESENTATION AND RESPONSE TO TREATMENT. AB - The clinical manifestations and prognosis of cutaneous leishmaniasis (CL) can be influenced by the immune response of the patient and the species of the parasite. A case of atypical clinical presentation of CL, with development of non characteristic lesions, poor response to therapy, and a long time to resolution is reported. Confirmatory laboratory tests included parasite detection, indirect immunofluorescence, Montenegro skin test, polymerase chain reaction, and parasite identification by multilocus enzyme electrophoresis. The parasite was identified as Leishmania braziliensis. The lesion was unresponsive to three complete courses of N-methylglucamine antimoniate intramuscular, and to treatment with pentamidine. The patient did not tolerate amphotericin B. The lesion finally receded after treatment with intravenous N-methylglucamine antimoniate. It is essential to ensure the accuracy of diagnosis and the appropriate treatment, which can include the use a second choice drug or a different route of administration. PMID- 27007565 TI - SURVIVAL CAPACITY OF Arcobacter butzleri INOCULATED IN POULTRY MEAT AT TWO DIFFERENT REFRIGERATION TEMPERATURES. AB - Arcobacter spp. are emerging enteropathogens and potential zoonotic agents that can be transmitted by food and water, being considered a public health risk. The high isolation rate of these bacteria from poultry products suggests that it may be a major source of human infections. One hallmark for differentiating the genus Arcobacter from Campylobacter includes their growing capacity at low temperatures (15-30 degrees C) under aerobic conditions. However, little is known about the population density variation of these bacteria at different refrigeration temperatures. The aim of this study was to determine the survival behavior of two different Arcobacter butzleri concentrations (10(4) CFU/mL and 10(7) CFU/mL) inoculated on chicken legs and held at two different refrigeration temperatures (4 and 10 degrees C) throughout storage time. Results have shown that A. butzleri had growing capacity both at 4 and 10 degrees C. No statistical difference between the survival trends was found for both bacterial concentrations and temperatures tested. This study shows that A. butzleri is a robust species with regard to storage temperature, and represents a potential health risk for poultry meat consumers. PMID- 27007564 TI - INTESTINAL AND PULMONARY INFECTION BY Cryptosporidium parvum IN TWO PATIENTS WITH HIV/AIDS. AB - We describe two patients with HIV/AIDS who presented pulmonary and intestinal infection caused by Cryptosporidium parvum, with a fatal outcome. The lack of available description of changes in clinical signs and radiographic characteristics of this disease when it is located in the extra-intestinal region causes low prevalence of early diagnosis and a subsequent lack of treatment. PMID- 27007566 TI - Leishmania infantum AS A CAUSATIVE AGENT OF CUTANEOUS LEISHMANIASIS IN THE STATE OF MATO GROSSO DO SUL, BRAZIL. AB - Cutaneous leishmaniasis is caused by different species of the Leishmania genus. Leishmania(Leishmania) infantum, causing cutaneous leishmaniasis, has been described in patients living in areas where visceral leishmaniasis is endemic. In this study, it was possible to characterize this species in seven slides from cutaneous tissue imprints from patients with cutaneous leishmaniasis in the State of Mato Grosso do Sul, Brazil. PMID- 27007567 TI - INTRODUCTION AND TRANSMISSION OF ZIKA VIRUS IN BRAZIL: NEW CHALLENGES FOR THE AMERICAS. PMID- 27007568 TI - A Shipping Container-Based Sterile Processing Unit for Low Resources Settings. AB - Deficiencies in the sterile processing of medical instruments contribute to poor outcomes for patients, such as surgical site infections, longer hospital stays, and deaths. In low resources settings, such as some rural and semi-rural areas and secondary and tertiary cities of developing countries, deficiencies in sterile processing are accentuated due to the lack of access to sterilization equipment, improperly maintained and malfunctioning equipment, lack of power to operate equipment, poor protocols, and inadequate quality control over inventory. Inspired by our sterile processing fieldwork at a district hospital in Sierra Leone in 2013, we built an autonomous, shipping-container-based sterile processing unit to address these deficiencies. The sterile processing unit, dubbed "the sterile box," is a full suite capable of handling instruments from the moment they leave the operating room to the point they are sterile and ready to be reused for the next surgery. The sterile processing unit is self-sufficient in power and water and features an intake for contaminated instruments, decontamination, sterilization via non-electric steam sterilizers, and secure inventory storage. To validate efficacy, we ran tests of decontamination and sterilization performance. Results of 61 trials validate convincingly that our sterile processing unit achieves satisfactory outcomes for decontamination and sterilization and as such holds promise to support healthcare facilities in low resources settings. PMID- 27007569 TI - Generation of cortical neurons from human induced-pluripotent stem cells by biodegradable polymeric microspheres loaded with priming factors. AB - Ischemic stroke is often associated with loss of cortical neurons leading to various neurological deficits. A cell replacement based on stem cell transplantation to repair the damaged brain requires the generation of specific neuronal subtypes. Recently, induced pluripotent stem cells have been used to generate various subtypes of neurons in vitro for transplantation in stroke damaged brains. However, whether these cells can be primed as neuronal precursors to become cortical projection neurons by means of biomaterials releasing differentiation factors is not known. Here, we report that microspheres of biodegradable poly(ester-amide) composed of adipic acid, L-phenyl-alanine and 1,4 butanediol, loaded with differentiation factors, can be used to fate human induced pluripotent stem cell-derived long-term expandable neuroepithelial-like stem cells to cortical projection neurons. The three factors, Wnt3A, BMP4 and cyclopamine, were released from loaded microspheres over at least one month following biphasic dynamic time course, promoting cortical differentiation of the cells in vitro. Microspheres did not evoke significant inflammatory response after transplantation into intact rodent brain. Our study shows the potential of biodegradable polymer microspheres to promote neuronal differentiation by continuous release of factors, thereby creating the appropriate microenvironment. This new strategy may improve the efficacy of stem cell-based therapeutic approaches. PMID- 27007570 TI - Characterisation of the Porphyromonas gingivalis Manganese Transport Regulator Orthologue. AB - PgMntR is a predicted member of the DtxR family of transcriptional repressors responsive to manganese in the anaerobic periodontal pathogen Porphyromonas gingivalis. Our bioinformatic analyses predicted that PgMntR had divalent metal binding site(s) with elements of both manganous and ferrous ion specificity and that PgMntR has unusual twin C-terminal FeoA domains. We produced recombinant PgMntR and four variants to probe the specificity of metal binding and its impact on protein structure and DNA binding. PgMntR dimerised in the absence of a divalent transition metal cation. PgMntR bound three Mn(II) per monomer with an overall dissociation constant Kd 2.0 x 10(-11) M at pH 7.5. PgMntR also bound two Fe(II) with distinct binding affinities, Kd1 2.5 x 10(-10) M and Kd2 <= 6.0 x 10( 8) M at pH 6.8. Two of the metal binding sites may form a binuclear centre with two bound Mn2+ being bridged by Cys108 but this centre provided only one site for Fe2+. Binding of Fe2+ or Mn2+ did not have a marked effect on the PgMntR secondary structure. Apo-PgMntR had a distinct affinity for the promoter region of the gene encoding the only known P. gingivalis manganese transporter, FB2. Mn2+ increased the DNA binding affinity of PgMntR whilst Fe2+ destabilised the protein-DNA complex in vitro. PgMntR did not bind the promoter DNA of the gene encoding the characterised iron transporter FB1. The C-terminal FeoA domain was shown to be essential for PgMntR structure/function, as its removal caused the introduction of an intramolecular disulfide bond and abolished the binding of Mn2+ and DNA. These data indicate that PgMntR is a novel member of the DtxR family that may function as a transcriptional repressor switch to specifically regulate manganese transport and homeostasis in an iron-dependent manner. PMID- 27007571 TI - Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase. AB - Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM 1) and proinflammatory cytokines (IL-6 and TNF-alpha) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-alpha and adhesion molecules (E selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-alpha, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR. PMID- 27007572 TI - Use of a Publicly Available Database to Determine the Impact of Diabetes on Length of Hospital Stay for Elective Orthopedic Procedures in California. AB - In California, 1 in 3 hospital beds are occupied by adults with diabetes. The aim of this study was to examine whether diabetes impacts length of stay (LOS) following common elective orthopedic procedures compared to nondiabetic individuals, and also the performance of hospitals across California for these procedures. Using the Public Use California Patient Discharge Data Files for 2010 2012, the authors examined LOS for elective discharges for hip, spine, or knee surgery (n = 318,861) from the total population of all discharges (n = 11,476,073) for 309 hospitals across California. In all, 16% of discharges had a codiagnosis of diabetes. Unadjusted average LOS was 3.11 days without and 3.40 days with diabetes (mean difference 0.29 [95% confidence interval (0.27, 0.31) days, P < 0.01]). After adjusting for covariates, diabetes no longer resulted in a significant difference in LOS. However, the presence of common comorbidities did significantly impact LOS. Average LOS for patients with diabetes also varied widely by hospital, ranging between -50% and +100% of the mean LOS for all hospitals. Diabetes does not prolong LOS after orthopedic procedures unless comorbidities are present. Nevertheless, across California there is significant variation in LOS between individual hospitals, which may inform the decision making process for prospective patients and payers. PMID- 27007573 TI - Hemocyanin from Shrimp Litopenaeus vannamei Has Antiproliferative Effect against HeLa Cell In Vitro. AB - Hemocyanin (HMC) has been shown to participate in multiple roles of immune defence. In this study, we investigated the antiproliferative effect and underpinning mechanism of HMC from Litopenaeus vannamei in vitro. Sulforhodamine B (SRB) assay indicated that HMC could dramatically inhibit the growth of HeLa cells, but not 293T cells under the same conditions. Moreover, typical morphological features of apoptosis in HeLa cells including the formation of apoptotic body-like vesicles, chromatin condensation and margination were observed by using 4, 6-diamidino-2- phenylindole dihydrochloride (DAPI) staining and fluorescence analysis. An apoptotic DNA ladder from 180 to 300 bp was also detected. Furthermore, 10 variation proteins associated with apoptosis pathway, viz. G3PDH isoforms 1/2 (G3PDH1/2), aldosereductase, ectodemal dysplasia receptor associated death receptor domain isoform CRA_a (EDARADD), heat shock 60kD protein 1 variant 1 (HSP60), heat shock 70kDa protein 5 precursor (HSP70), heat shock protein 90kDa beta member 1 precursor (HSP90), 14-3-3 protein zeta/delta, Ran and ubiquitin activating enzyme E1(UBE1), were identified from HMC-treated HeLa cells by the proteomic and quantitative real-time RT-PCR strategies. Importantly, the reactive oxygen species (ROS), mitochondrial membrane potential (Deltapsim) and caspase-9/3 activities were changed significantly in HMC-treated HeLa cells. Together, the data suggests that L. vannamei HMC mediates antiproliferative properties through the apoptosis mechanism involving the mitochondria triggered pathway. PMID- 27007574 TI - Higher Risk of Thyroid Disorders in Young Patients with Type 1 Diabetes: A 12 Year Nationwide, Population-Based, Retrospective Cohort Study. AB - BACKGROUND: The association between type 1 diabetes and thyroid autoimmunity has been studied in various populations, but seldom on Taiwanese children and adolescents. Therefore, the aim of this study was to examine the incidence of autoimmune thyroid disorders in Taiwanese children and adolescent patients with type 1 diabetes, based on data from a nationwide, population-based, health claims database. METHODS: Using Taiwan's National Health Insurance Research Database, we identified 3,652 patients with type 1 diabetes between 2000 and 2012. A comparison cohort was assembled, which consisted of five patients without type 1 diabetes, based on frequency matching for sex and 3-year age interval, for each patient with type 1 diabetes. Both groups were followed until diagnosis of thyroid disorders or the end of the follow-up period. Poisson regression models were used to calculate incidence rate ratios for the thyroid disorders between the type 1 diabetes cohort and the comparison cohort. RESULTS: Simple and unspecified goiter (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 240), thyrotoxicosis (ICD-9-CM code 242), unspecified hypothyroidism (ICD-9-CM code 244.9), and thyroiditis (ICD-9-CM code 245) showed significantly higher incidences in the type 1 diabetes cohort compared with the control cohort, with incidence rate ratios of 2.74, 6.95, 6.54, 16.07, respectively. CONCLUSIONS: Findings from this nationwide, population-based cohort study showed that the incidences of autoimmune thyroid disorders were significantly higher in Taiwanese children and adolescents with type 1 diabetes compared with those without the disease. PMID- 27007575 TI - Suicide Reporting on Front Pages of Major Newspapers in Taiwan Violating Reporting Recommendations Between 2001 and 2012. AB - Media reporting can lead to the acceptance of incorrect ideas and information by the general public, which in turn can impact behavior. A number of studies have found that suicide reporting in the media can lead to an increase in the suicide rate or copycat suicides. Therefore, the aims of this study are to (a) investigate front-page reporting of suicide in four major newspapers in Taiwan; (b) investigate violation of recommendations for reporting suicide by the four major newspapers in Taiwan; and (c) investigate the impact of important events and government policy on front-page reporting of suicide (i.e., the effect of the Apple Daily newspaper entering the market, and the start of media monitoring). We carried out content analysis of reports of suicide on the front pages of the four newspapers with the highest rates of readership in Taiwan (China Times, Liberty Times, Apple Daily, and United Daily News) between 2001 and 2012. We used the chi squared test, chi-squared test for trend, and analysis of variance to analyze trends in violation of reporting recommendations and potential associated factors. We found that (a) suicide was most commonly reported as a front-page headline and as a whole-page spread by the four major newspapers in Taiwan, with many reports including photographs; (b) reporting of suicide by the four major newspapers in Taiwan frequently violated World Health Organization (WHO) recommendations for suicide reporting in the media; (c) following the entry of the Apple Daily newspaper into the Taiwanese market, reporting approaches to suicide by the other three major newspapers changed to more sensational photos and texts; and (d) monitoring of suicide reporting by the Taiwan Suicide Prevention Center appears to have been only partially effective. In summary, reporting of suicide by the four major newspapers in Taiwan could be further improved. Effective regulation of suicide reporting by newspapers could reduce the impact of this reporting on readers. In addition, regular assessment of observance of the WHO recommendations for suicide reporting by newspapers is an important part of suicide prevention. PMID- 27007576 TI - Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence. AB - Objectives alpha2C-adrenoceptors (alpha2C-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism alpha2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated alpha2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of alpha2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n = 516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillary sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of alpha2CDel322-325-AR in suicide (9%, n = 236) and non-suicide victims (11%, n = 280) was similar. Genotype frequencies for the alpha2CDel322-325-AR polymorphism in depressed (15%, n = 39) and schizophrenic subjects (18%, n = 39) were higher than in controls (7%, n = 187), but these differences did not reach statistical significance (P = 0.125 and P = 0.063, respectively). A selective and significant association of alpha2CDel322 325-AR polymorphism with opiate abuse and dependence was found (23%, n = 35, P = 0.011). Conclusions Our results indicate that alpha2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies. PMID- 27007577 TI - Design of Small Intramolecular Singlet Fission Chromophores: An Azaborine Candidate and General Small Size Effects. AB - We report the first attempt to design small intramolecular singlet fission chromophores, with the aid of quantum chemistry and explicitly simulating the time evolution of state populations using quantum dynamics method. We start with three previously proposed azaborine-substituted intermolecular singlet fission chromophores. Through analyzing their frontier orbital amplitudes, we select a BN substituted azulene as the building block. Covalently connecting two such monomers and tuning their relative configuration, we examine three dimers. One dimer is found to be an eminent candidate: the triplet-pair state is quickly formed within 1 ps, and the two triplets are ready to be disentangled. We elucidate the general small size effects in intramolecular singlet fission and focus on specific aspects which should be taken care of when manipulating the fission rate through steric hindrance. PMID- 27007579 TI - The Lived Experiences of Sexual Desire Among Chinese-Canadian Men and Women. AB - How North American Chinese conceptualize and experience sexual desire is not well understood, and may have implications for understanding cross-cultural differences in sexual functioning. This study examined narratives of sexual desire among Chinese men and women in Canada. Ten each of Chinese men (age: M = 24.0, range = 18-42) and women (age: M = 23.5, range = 19-38) took part in semi structured interviews in which they were invited to share personal accounts of sexual desire. A phenomenological analysis of participants' responses showed men and women described desire as having genital, nongenital-physical, and cognitive emotional components. Chinese cultural prohibitions against sexuality, particularly pronounced in women, were a common inhibitor of desire. Relationship factors appeared as a frequently endorsed context and target of desire. These findings suggest that relationship context is of paramount importance in Chinese individuals and that previous findings of low sexual functioning in this group may be due to inhibition from cultural factors. However, the experience of desire in Chinese individuals is also in many ways similar to that of existing conceptualizations from Western samples. PMID- 27007580 TI - Effects of a Gestational Weight Gain Restriction Program for Obese Pregnant Women: Children's Weight Development during the First Five Years of Life. AB - BACKGROUND: Maternal prepregnancy obesity (BMI >=30 kg/m(2)) and excessive gestational weight gain (GWG) have shown a strong positive association with a higher BMI and risk of obesity in the offspring. The aim of this study is to estimate the effect of a GWG restriction program for obese pregnant women on the children's BMI at 5 years of age and weight-for-length/height (WL/H) development from 2 months of age until 5 years of age. METHODS: This was a follow-up study of 302 children (137 children in an intervention group and 165 children in a control group) whose mothers participated in a weight gain restriction program during pregnancy. RESULTS: BMI at five years of age did not differ between girls and boys in the intervention and control group. The degree of maternal GWG, <7 kg or >=7 kg, did not affect the offspring's WL/H. Compared with Swedish reference data, just over half of the children in both the intervention and control group had a BMI within the average range, whereas slightly more than one-third of the children had a higher BMI. CONCLUSION: Despite a comprehensive gestational intervention program for obese women containing individual weekly visits and opportunity to participate in aqua aerobic classes, there were no differences between BMI or weight development among the offspring at 5 years of age in the intervention and control group. PMID- 27007581 TI - CP II. PMID- 27007582 TI - The Opioid Abuse Blame Game. PMID- 27007578 TI - PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. AB - BACKGROUND: The role of image-guided surveillance as compared with planned neck dissection in the treatment of patients with squamous-cell carcinoma of the head and neck who have advanced nodal disease (stage N2 or N3) and who have received chemoradiotherapy for primary treatment is a matter of debate. METHODS: In this prospective, randomized, controlled trial, we assessed the noninferiority of positron-emission tomography-computed tomography (PET-CT)-guided surveillance (performed 12 weeks after the end of chemoradiotherapy, with neck dissection performed only if PET-CT showed an incomplete or equivocal response) to planned neck dissection in patients with stage N2 or N3 disease. The primary end point was overall survival. RESULTS: From 2007 through 2012, we recruited 564 patients (282 patients in the planned-surgery group and 282 patients in the surveillance group) from 37 centers in the United Kingdom. Among these patients, 17% had nodal stage N2a disease and 61% had stage N2b disease. A total of 84% of the patients had oropharyngeal cancer, and 75% had tumor specimens that stained positive for the p16 protein, an indicator that human papillomavirus had a role in the causation of the cancer. The median follow-up was 36 months. PET-CT-guided surveillance resulted in fewer neck dissections than did planned dissection surgery (54 vs. 221); rates of surgical complications were similar in the two groups (42% and 38%, respectively). The 2-year overall survival rate was 84.9% (95% confidence interval [CI], 80.7 to 89.1) in the surveillance group and 81.5% (95% CI, 76.9 to 86.3) in the planned-surgery group. The hazard ratio for death slightly favored PET-CT-guided surveillance and indicated noninferiority (upper boundary of the 95% CI for the hazard ratio, <1.50; P=0.004). There was no significant difference between the groups with respect to p16 expression. Quality of life was similar in the two groups. PET-CT-guided surveillance, as compared with neck dissection, resulted in savings of L1,492 (approximately $2,190 in U.S. dollars) per person over the duration of the trial. CONCLUSIONS: Survival was similar among patients who underwent PET-CT-guided surveillance and those who underwent planned neck dissection, but surveillance resulted in considerably fewer operations and it was more cost-effective. (Funded by the National Institute for Health Research Health Technology Assessment Programme and Cancer Research UK; PET-NECK Current Controlled Trials number, ISRCTN13735240.). PMID- 27007584 TI - Systematic Reviews Published in the October 2015 Issue of the Cochrane Library. AB - The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online (http://www.thecochranelibrary.com). The October 2015 issue (fourth DVD for 2015) contains 6622 complete reviews, 2429 protocols for reviews in production, and 36,600 short summaries of systematic reviews published in the general medical literature (this short summary database is no longer being updated). In addition, there are citations of 848,000 randomized controlled trials, and 15,700 cited papers in the Cochrane Methodology Register. The Health Technology Assessment database contains some 15,000 citations. One hundred and nine new reviews have been published in the previous 3 months, of which six have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 5.939. Readers are encouraged to access the full report for any articles of interest as only a brief commentary is provided. PMID- 27007583 TI - Office-Based Buprenorphine Versus Clinic-Based Methadone: A Cost-Effectiveness Analysis. AB - The objective of this analysis was to compare the cost-effectiveness of clinic based methadone maintenance therapy (MMT) and office-based buprenorphine maintenance therapy (BMT) from the perspective of third-party payers in the United States. The authors used a Markov cost-effectiveness model. A hypothetical cohort of 1000 adult, opioid-dependent patients was modeled over a 1-year time horizon. Patients were allowed to transition between the health states of in opioid dependence treatment and either abusing or not abusing opioids, or to have dropped out of treatment. Probabilities were derived from randomized clinical trials comparing methadone and buprenorphine. Costs included drug and administration, clinic visits, and therapy sessions. Effectiveness outcomes examined were (1) retention in the treatment program and (2) opioid abuse-free weeks. For retention in treatment at 1 year, MMT was more costly ($4,613 vs. $4,155) and more effective (20.3% vs. 15.9%) than BMT, resulting in an incremental cost-effectiveness ratio (ICER) of $10,437 per additional patient retained in treatment. MMT was also more effective than BMT in terms of opioid abuse-free weeks (9.2 vs. 9.1 weeks), resulting in an ICER of $8,515 per opioid abuse-free week gained. One-way sensitivity analyses found costs per week of MMT to have the largest impact on the retention-in-treatment outcome, whereas the probability of dropping out with MMT had the greatest impact on opioid abuse-free weeks. The authors conclude that MMT is cost-effective compared with BMT for the treatment of patients with opioid dependence. However, the treatment of substance abuse is complex, and decision makers should also consider individual patient characteristics when making coverage decisions. PMID- 27007587 TI - Factors Affecting the Stabilization of Polyproline II Helices in a Hydrophobic Environment. AB - Several parameters have a critical importance for the stabilization of either polyproline I (PPI) or polyproline II (PPII) helices in a hydrophobic environment. Among them, it was found out that the concentration is crucial as polyprolines at 3 mM concentration stably fold in PPII helices, that are organized in aggregates stable even after several days and are detectable by dynamic light scattering analysis. In more diluted concentration the same molecules stably fold in PPI helices, and no aggregates are found. In contrast, the introduction of a (4S,5R)-4-carboxy-5-methyloxazolidin-2-one (L-Oxd) moiety always inhibits the formation of the PPI helix, regardless of the L-Oxd position and the solution concentration. PMID- 27007588 TI - Bilateral retinal hemorrhages following finger pressure against the soft palate (|??????) in recessive CRB1-related retinopathy. AB - PURPOSE: To report two siblings with CRB1-related retinopathy who developed retinal hemorrhages following village traditional treatment of upward finger pressure against the soft palate ([Formula: see text]). METHODS: A retrospective case series. RESULTS: Two sisters were clinically diagnosed and genetically confirmed to have recessive CRB1-related retinal dystrophy. The family did not accept the condition as non-treatable and took both sisters for a traditional village therapy, consisting of several sessions of intense upward index finger pressure by the healer against the soft palate for each child. When examined following this therapy, both sisters had bilateral pre-retinal hemorrhages which were not present before the intervention and resolved without sequelae over the next several months. CONCLUSIONS: The traditional village therapy may have compromised retinal venous outflow and/or provoked a Valsalva phenomenon, leading to the bilateral retinal hemorrhages. The fact that this occurred bilaterally and in both sisters supports the concept of relative vessel wall incompetence as part of CRB1-related retinopathy. PMID- 27007593 TI - Shear-wave elastography and greyscale assessment of palpable probably benign masses: is biopsy always required? AB - OBJECTIVE: To establish if palpable breast masses with benign greyscale ultrasound features that are soft on shear-wave elastography (SWE) (mean stiffness <50 kPa) have a low enough likelihood of malignancy to negate the need for biopsy or follow-up. METHODS: The study group comprised 694 lesions in 682 females (age range 17-95 years, mean age 56 years) presenting consecutively to our institution with palpable lesions corresponding to discrete masses at ultrasound. All underwent ultrasound, SWE and needle core biopsy. Static greyscale images were retrospectively assigned Breast Imaging Reporting and Data System (BI-RADS) scores by two readers blinded to the SWE and pathology findings, but aware of the patient's age. A mean stiffness of 50 kPa was used as the SWE cut-off for calling a lesion soft or stiff. Histological findings were used to establish ground truth. RESULTS: No cancer had benign characteristics on both modalities. 466 (99.8%) of the 467 cancers were classified BI-RADS 4a or above. The one malignant lesion classified as BI-RADS 3 was stiff on SWE. 446 (96%) of the 467 malignancies were stiff on SWE. No cancer in females under 40 years had benign SWE features. 74 (32.6%) of the 227 benign lesions were BI-RADS 3 and soft on SWE; so, biopsy could potentially have been avoided in this group. CONCLUSION: Lesions which appear benign on greyscale ultrasound and SWE do not require percutaneous biopsy or short-term follow-up, particularly in females under 40 years. ADVANCES IN KNOWLEDGE: None of the cancers had benign characteristics on both greyscale ultrasound and SWE, and 32% of benign lesions were BI-RADS 3 and soft on SWE; lesions that are benign on both ultrasound and SWE may not require percutaneous biopsy or short-term follow-up. PMID- 27007594 TI - Efficacy of Sucralfate Mouth Wash in Prevention of 5-fluorouracil Induced Oral Mucositis: A Prospective, Randomized, Double-Blind, Controlled Trial. AB - Sucralfate has been used for the prevention and treatment of radiotherapy- and chemotherapy-induced stomatitis and mucositis in a number of studies, but the results are contradictory. To answer such discrepancies, the present study was designed to evaluate the efficacy of sucralfate mouthwash in prevention of 5 fluorouracil (5-FU)-induced oral mucositis in patients with gastrointestinal malignancies. Patients with gastrointestinal cancers receiving 5-FU-based chemotherapy regimens were included in this randomized, blinded, controlled trial and were randomly allocated to either sucralfate mouthwash (every 6 h) or placebo. The patients were visited at fifth and tenth day of trial; the presence and severity of oral mucositis and the intensity of pain were assessed. The patients receiving sucralfate experienced lower frequency and severity of mucositis (76% vs. 38.5%, P = 0.005 and 84 vs. 38.5%, P < 0.001, respectively) and less intense pain (2.5 +/- 2.2 vs. 5.08 +/- 3.82, P = 0.004 and 1.33 +/- 0.86 vs. 4.12 +/- 3.5, P = 0.001, respectively) compared with the placebo group both at day 5 and day 10. Within the sucralfate group, a decrease in frequency and severity of mucositis was observed throughout the trial period, while in the placebo group no such effect was observed. Sucralfate mouthwash reduced the frequency and severity of 5-FU-induced oral mucositis in patients with gastrointestinal malignancies compared with placebo, indicating its efficacy in the prevention of chemotherapy-induced mucositis. PMID- 27007595 TI - Emerging drugs for graft-versus-host disease. AB - INTRODUCTION: Graft-versus-host disease (GVHD) leads to significant morbidity and mortality after allogeneic stem cell transplantation. While corticosteroids alone are adequate in some cases, they are often insufficient, leading to poor quality of life associated with the symptoms of disease, or mortality from infection and GVHD. Moreover, corticosteroids have significant side effects and often do not lead to durable responses. New therapies are needed to improve the development and progression of acute and chronic GVHD. AREAS COVERED: We discuss the spectrum of emerging drugs for GVHD prevention and therapy. Cellular therapies will be briefly discussed. The available pre-clinical and clinical data regarding monoclonal antibodies, interleukin-2, alpha-1 antitrypsin, histone deacetylase inhibitors, tyrosine kinase inhibitors, and proteasome inhibitors will be reviewed. EXPERT OPINION: Although therapies emerging for GVHD remain promising, most of these drugs are still in early phase clinical trials and require randomized comparisons before formal conclusions can be drawn. It is likely that in the near future some of these agents will show improvements in response when compared with corticosteroids alone. Although it is difficult to predict which of these agents will be most promising, alpha-1 antitrypsin, ruxolitinib and interleukin-2 have demonstrated encouraging results. PMID- 27007596 TI - Development and evaluation of two instruments for assessing screening, brief intervention, and referral to treatment (SBIRT) competency. AB - BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) is shown to be effective in identifying, intervening with, and making appropriate referrals for patients with unhealthy alcohol use. SBIRT training consists of knowledge-based and skill-based components and has increased the use of screening and intervention skills in clinical settings. This article reports on the development and evaluation of 2 SBIRT proficiency checklists for use across institutions to assess SBIRT skills in both simulated and clinical encounters. METHODS: A national panel of 16 experts identified 137 discrete SBIRT skills items for the checklists. From this final list, 2 proficiency checklists were derived: the SBIRT Proficiency Checklist (SPC), composed of 22 questions for videotaped interviews, and the Clinical SBIRT Proficiency Checklist (CSPC), composed of 13 questions for direct clinical observation. An evaluation was conducted to test the reliability of the SPC and to assess the utility of the CSPC. RESULTS: Two checklists for assessing SBIRT proficiency were developed by a collaborative workgroup. Fleiss' kappa analyses indicated moderate agreement. In addition, faculty recorded satisfaction with the CSPC for assessing residents on their SBIRT performance during clinical encounters. CONCLUSIONS: The SPC and the CSPC are practical tools for assessing competence with SBIRT and are easily integrated as standard instruments in a wide range of training settings. Future advancements to the checklists and their evaluation include modification of the SPC rating scale to be consistent with the CSPC, developing a training program for using the checklists, and further testing to improve interrater reliability. PMID- 27007598 TI - The Value of miR-299-5p in Diagnosis and Prognosis of Intestinal-Type Gastric Adenocarcinoma. AB - MicroRNAs (miRNAs) are a class of non-coding RNAs, containing about 22 nucleotides and having a pivotal function in various cellular processes. The oncogenic and tumor suppressor roles of miRNAs have been identified in cancers especially in gastric cancer, which is one of the most prevalent cancers. MiR-299 5p is located in the imprinted Dlk1-Dio3 region in chromosome 14q32. Aberrant expression of miR-299-5p was determined in solid and blood cancers. The current study was performed to assess the expression pattern of miR-299-5p in intestinal type gastric adenocarcinoma and compare it with the normal adjacent counterparts. The expression level of miR-299-5p was investigated in forty fresh specimens which were obtained from gastric cancer patients during endoscopy. Moreover, the association of aberrant expression of miR-299-5p and clinicopathological features, as well as the susceptibility of miR-299-5p as a tumor marker, was determined. The result of qRT-PCR revealed the downregulation of miR-299-5p in intestinal-type gastric adenocarcinoma compared with adjacent tumor-free tissues (P < 0.001); this misregulation can be used as a tumor marker. Analysis of miR 299-5p misregulation did not reveal a significant correlation with clinical features. The result obtained from the present study revealed the significant downregulation of miR-299-5p in intestinal-type gastric adenocarcinoma which is consistent with previous studies showing miR-299-5p downregulation in other types of cancers. The data obtained from the current study suggest basic information which can be very helpful for future research in the field of diagnosis and treatment of gastric cancer. PMID- 27007597 TI - European Guidelines on Pericardial Diseases: a Focused Review of Novel Aspects. AB - Pericardial diseases are not uncommon in daily clinical practice. The spectrum of these syndromes includes acute and chronic pericarditis, pericardial effusion, constrictive pericarditis, congenital defects, and neoplasms. The extent of the high-quality evidence on pericardial diseases has expanded significantly since the first international guidelines on pericardial disease management were published by the European Society of Cardiology in 2004. The clinical practice guidelines provide a useful reference for physicians in selecting the best management strategy for an individual patient by summarizing the current state of knowledge in a particular field. The new clinical guidelines on the diagnosis and management of pericardial diseases that have been published by the European Society of Cardiology in 2015 represent such a tool and focus on assisting the physicians in their daily clinical practice. The aim of this review is to outline and emphasize the most clinically relevant new aspects of the current guidelines as compared with its previous version published in 2004. PMID- 27007599 TI - Eucapnic Voluntary Hyperpnea: Gold Standard for Diagnosing Exercise-Induced Bronchoconstriction in Athletes? AB - In athletes, a secure diagnos is of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the 'gold standard'. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a 'gold standard' test for EIB. PMID- 27007600 TI - Evolutionary Dynamics of Chronic Myeloid Leukemia Progression: the Progression Inhibitory Effect of Imatinib. AB - The t(9;22) translocation that causes chronic myeloid leukemia (CML) drives both transformation and the progression process that eventually results in the disease changing to acute leukemia. Constitutively activated Bcr-Abl signaling in CML creates high levels of reactive oxygen species (ROS) that produce 8-oxo-guanine in DNA; this is mutagenic and causes chronic phase (CP) progression to blast phase (BP). We modeled three types of mutations involved in this progression: mutations that result in myeloid progenitor cells proliferating independently of external growth factors; mutations causing failure of myeloid progenitor cells to differentiate; and mutations that enable these cells to survive independently of attachment to marrow stroma. We further modeled tyrosine kinase inhibitors (TKI) as restoring myeloid cell apoptosis and preventing ROS-driven mutagenesis, and mutations that cause TKI resistance. We suggest that the unusually low rate of resistance to TKI arises because these drugs deplete ROS, which in turn decrease mutation rates. PMID- 27007602 TI - Study of Spiritual Intelligence and Adjustment Among Arts and Science College Students. AB - A study to evaluate the relationship between the spiritual intelligence and adjustment among the college students was conducted on a sample of 250 students in six various colleges of Tuticorin district, Tamil Nadu, India. Gender, religion, community, major subject, educational qualification of father and mother, student locality, college type, father and mother's occupation and monthly family income (n = 11 variables) were chosen for the study. Test of significance for spiritual intelligence and adjustment was studied and found them nonsignificant except student locality, found to be significant. Two valid and reliable instruments were used to assess student's spiritual intelligence and adjustment. Correlation and Chi-square analysis using structural equation model were used to analyze these data. Correlation analysis showed significant relationship between the variables among the college students (n = 250). Chi square analysis of association between adjustments of college students showed that most variables are nonsignificant unlike father's educational qualification and mother's occupation. The results disclosed the significant positive relationship with spiritual intelligence and adjustment among adolescents. PMID- 27007601 TI - Recent Advances in Application of Pharmacogenomics for Biotherapeutics. AB - Biotherapeutics (BTs), one of the fastest growing classes of drug molecules, offer several advantages over the traditional small molecule pharmaceuticals because of their relatively high specificity, low off-target effects, and biocompatible metabolism, in addition to legal and logistic advantages. However, their clinical utility is limited, among other things, by their high immunogenic potential and/or variable therapeutic efficacy in different patient populations. Both of these issues, also commonly experienced with small molecule drugs, have been addressed effectively in a number of cases by the successful application of pharmacogenomic tools and approaches. In this introductory article of the special issue, we review the current state of application of pharmacogenomics to BTs and offer suggestions for further expansion of the field. PMID- 27007603 TI - Efficient Catalytic Ozonation over Reduced Graphene Oxide for p-Hydroxylbenzoic Acid (PHBA) Destruction: Active Site and Mechanism. AB - Nanocarbons have been demonstrated as promising environmentally benign catalysts for advanced oxidation processes (AOPs) upgrading metal-based materials. In this study, reduced graphene oxide (rGO) with a low level of structural defects was synthesized via a scalable method for catalytic ozonation of p-hydroxylbenzoic acid (PHBA). Metal-free rGO materials were found to exhibit a superior activity in activating ozone for catalytic oxidation of organic phenolics. The electron rich carbonyl groups were identified as the active sites for the catalytic reaction. Electron spin resonance (ESR) and radical competition tests revealed that superoxide radical ((*)O2(-)) and singlet oxygen ((1)O2) were the reactive oxygen species (ROS) for PHBA degradation. The intermediates and the degradation pathways were illustrated from mass spectroscopy. It was interesting to observe that addition of NaCl could enhance both ozonation and catalytic ozonation efficiencies and make .O2(-) as the dominant ROS. Stability of the catalysts was also evaluated by the successive tests. Loss of specific surface area and changes in the surface chemistry were suggested to be responsible for catalyst deactivation. PMID- 27007605 TI - Detection of error-related negativity in complex visual stimuli: a new neuroergonomic arrow in the practitioner's quiver. AB - Brain processes responsible for the error-related negativity (ERN) evoked response potential (ERP) have historically been studied in highly controlled laboratory experiments through presentation of simple visual stimuli. The present work describes the first time the ERN has been evoked and successfully detected in visual search of complex stimuli. A letter flanker task and a motorcycle conspicuity task were presented to participants during electroencephalographic (EEG) recording. Direct visual inspection and subsequent statistical analysis of the resultant time-locked ERP data clearly indicated that the ERN was detectable in both groups. Further, the ERN pattern did not differ between groups. Such results show that the ERN can be successfully elicited and detected in visual search of complex static images, opening the door to applied neuroergonomic use. Harnessing the brain's error detection system presents significant opportunities and complex challenges, and implication of such are discussed in the context of human-machine systems. Practitioner Summary: For the first time, error-related negativity (ERN) has been successfully elicited and detected in a visually complex applied search task. Brain-process-based error detection in human-machine systems presents unique challenges, but promises broad neuroergonomic applications. PMID- 27007604 TI - Piromelatine ameliorates memory deficits associated with chronic mild stress induced anhedonia in rats. AB - RATIONALE: Previous studies have demonstrated that piromelatine (a melatonin and serotonin 5-HT1A and 5-HT1D agonist) exerts an antidepressant activity in rodent models of acute stress and improves cognitive impairments in a rat model of Alzheimer's disease (AD). However, the role of piromelatine in chronic stress induced memory dysfunction remains unclear. OBJECTIVE: The aim of this study was to determine whether piromelatine ameliorates chronic mild stress (CMS)-induced memory deficits and explore the underlying mechanisms. METHODS: Rats were exposed randomly to chronic mild stressors for 7 weeks to induce anhedonia (reflected by a significant decrease in sucrose intake), which was used to select rats vulnerable (CMS-anhedonic, CMSA) or resistant (CMS-resistant, CMSR) to stress. Piromelatine (50 mg/kg) was administered daily during the last 2 weeks of CMS. The tail suspension and forced swimming tests were adopted to further characterize vulnerable and resilient rats. The Y-maze and novel object recognition (NOR) tests were used to evaluate memory performance. Brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), phosphorylated CREB (pCREB), and cytogenesis were measured in the hippocampus. RESULTS: We found that only CMSA rats displayed significant increases in immobility time in the tail suspension and forced swimming tests; memory deficits in the Y-maze and NOR tests; significant decreases in hippocampal BDNF, CREB, and pCREB expression; and cytogenesis. All these anhedonia-associated effects were reversed by piromelatine. CONCLUSIONS: Piromelatine ameliorates memory deficits associated with CMS-induced anhedonia in rats and this effect may be mediated by restoring hippocampal BDNF, CREB, and cytogenesis deficits. PMID- 27007606 TI - Phase and precession evolution in the Burgers equation. AB - We present a phenomenological study of the phase dynamics of the one-dimensional stochastically forced Burgers equation, and of the same equation under a Fourier mode reduction on a fractal set. We study the connection between coherent structures in real space and the evolution of triads in Fourier space. Concerning the one-dimensional case, we find that triad phases show alignments and synchronisations that favour energy fluxes towards small scales --a direct cascade. In addition, strongly dissipative real-space structures are associated with entangled correlations amongst the phase precession frequencies and the amplitude evolution of Fourier triads. As a result, triad precession frequencies show a non-Gaussian distribution with multiple peaks and fat tails, and there is a significant correlation between triad precession frequencies and amplitude growth. Links with dynamical systems approach are briefly discussed, such as the role of unstable critical points in state space. On the other hand, by reducing the fractal dimension D of the underlying Fourier set, we observe: i) a tendency toward a more Gaussian statistics, ii) a loss of alignment of triad phases leading to a depletion of the energy flux, and iii) the simultaneous reduction of the correlation between the growth of Fourier mode amplitudes and the precession frequencies of triad phases. PMID- 27007607 TI - Statistics of the dissipated energy in driven diffusive systems. AB - Understanding the physics of non-equilibrium systems remains one of the major open questions in statistical physics. This problem can be partially handled by investigating macroscopic fluctuations of key magnitudes that characterise the non-equilibrium behaviour of the system of interest; their statistics, associated structures and microscopic origin. During the last years, some new general and powerful methods have appeared to delve into fluctuating behaviour that have drastically changed the way to address this problem in the realm of diffusive systems: macroscopic fluctuation theory (MFT) and a set of advanced computational techniques that make it possible to measure the probability of rare events. Notwithstanding, a satisfactory theory is still lacking in a particular case of intrinsically non-equilibrium systems, namely those in which energy is not conserved but dissipated continuously in the bulk of the system (e.g. granular media). In this work, we put forward the dissipated energy as a relevant quantity in this case and analyse in a pedagogical way its fluctuations, by making use of a suitable generalisation of macroscopic fluctuation theory to driven dissipative media. PMID- 27007608 TI - Imaging Factors That Influence Surgical Margins After Preoperative 125I Radioactive Seed Localization of Breast Lesions: Comparison With Wire Localization. AB - OBJECTIVE: The objective of this study was to compare the potential influence of imaging variables on surgical margins after preoperative radioactive seed localization (RSL) and wire localization (WL) techniques. MATERIALS AND METHODS: A total of 565 women with 660 breast lesions underwent RSL or WL between May 16, 2012, and May 30, 2013. Patient age, lesion type (mass, calcifications, mass with associated calcifications, other), lesion size, number of seeds or wires used, surgical margin status (close positive or negative margins), and reexcision and mastectomy rates were recorded. RESULTS: Of 660 lesions, 127 (19%) underwent RSL and 533 (81%) underwent WL preoperatively. Mean lesion size was 1.8 cm in the RSL group and 1.8 cm in the WL group (p = 0.35). No difference in lesion type was identified in the RSL and WL groups (p = 0.63). RSL with a single seed was used in 105 of 127 (83%) RSLs compared with WL with a single wire in 349 of 533 (65%) WLs (p = 0.0003). The number of cases with a close positive margin was similar for RSLs (26/127, 20%) and WLs (104/533, 20%) (p = 0.81). There was no difference between the RSL group and the WL group in close positive margin status (20% each, p = 0.81), reexcision rates (20% vs 16%, respectively; p = 0.36), or mastectomy rates (6% each, p = 0.96). Lesions containing calcifications were more likely to require more than one wire (odds ratio [OR], 4.44; 95% CI, 2.8-7.0) or more than one seed (OR, 7.03; 95% CI, 1.6-30.0) when compared with masses alone (p < 0.0001). Increasing lesion size and the presence of calcifications were significant predictors of positive margins, whereas the use of more than one wire or seed was not (OR, 0.9; 95% CI, 0.5-1.5) (p = 0.75). CONCLUSION: Close positive margin, reexcision, and mastectomy rates remained similar in the WL group and RSL group. The presence of calcifications and increasing lesion size increased the odds of a close positive margin in both the WL and RSL groups, whereas the use of one versus more than one seed or wire did not. PMID- 27007609 TI - Evaluation of Monitoring Schemes for Wastewater-Based Epidemiology to Identify Drug Use Trends Using Cocaine, Methamphetamine, MDMA and Methadone. AB - Wastewater-based epidemiology is increasingly being used as a tool to monitor drug use trends. To minimize costs, studies have typically monitored a small number of days. However, cycles of drug use may display weekly and seasonal trends that affect the accuracy of monthly or annual drug use estimates based on a limited number of samples. This study aimed to rationalize sampling methods for minimizing the number of samples required while maximizing information about temporal trends. A range of sampling strategies were examined: (i) targeted days (e.g., weekends), (ii) completely random or stratified random sampling, and (iii) a number of sampling strategies informed by known weekly cycles in drug use data. Using a time-series approach, analysis was performed for four drugs (MDMA, methamphetamine, cocaine, methadone) collected through a continuous sampling program over 14 months. Results showed, for drugs with weekly cycles (MDMA, methamphetamine and cocaine in this sample), sampling strategies which made use of those weekly cycles required fewer samples to obtain similar information as sampling 5 days per week and had better accuracy than stratified random sampling techniques. PMID- 27007610 TI - Dorsal raphe nucleus and harm avoidance: A resting-state investigation. AB - The temperament dimension of harm avoidance defines an individual's biological tendency to exhibit altering levels of anxious, inhibiting, and cautious behavior. High harm avoidance and anxiety are highly comorbid, likely due to activity in similar neural circuitries involving the dorsal raphe nucleus. Despite the many investigations that have explored personality factors and brain function, none have determined the influence of ongoing activity within dorsal raphe networks on harm avoidance. The aim of this study was to explore such a relationship. In 62 healthy subjects, a series of 180 functional magnetic resonance images covering the entire brain were collected, and each subject completed the 240-item TCI-R questionnaire. Independent component analyses were performed to define the dorsal raphe network and then to determine the regions significantly correlated with harm avoidance. The independent component analyses revealed three signal intensity fluctuation maps encompassing the dorsal raphe nucleus, showing interactions with regions of the amygdala, hippocampus, nucleus accumbens, and prefrontal, insular, and cingulate cortices. Within these systems, the resting signal intensity was significantly coupled to harm avoidance in the bilateral basal amygdala, bilateral ventral hippocampus, bilateral insula, bilateral nucleus accumbens, and medial prefrontal cortex. Note that we could not measure serotonergic output, but instead measured signal changes in the dorsal raphe that likely reflect synaptic activity. These data provide evidence that at rest, signal intensity fluctuations within the dorsal raphe networks are related to harm avoidance. Given the strong relationship between harm avoidance and anxiety-like behaviors, it is possible that ongoing activity within this identified neural circuitry can contribute to an individual developing anxiety disorders. PMID- 27007611 TI - Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists. AB - 2-Cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[2-(phenylsulfanyl)ethyl]guanidine (UR PI376, 1) is a potent and selective agonist of the human histamine H4 receptor (hH4R). To gain information on the active conformation, we synthesized analogues of 1 with a cyclopentane-1,3-diyl linker. Affinities and functional activities were determined at recombinant hHxR (x: 1-4) subtypes on Sf9 cell membranes (radioligand binding, [(35)S]GTPgammaS, or GTPase assays) and in part in luciferase assays on human or mouse H4R (HEK-293 cells). The most potent H4R agonists among 14 racemates were separated by chiral HPLC, yielding eight enantiomerically pure compounds. Configurations were assigned based on X-ray structures of intermediates and a stereocontrolled synthetic pathway. (+)-2-Cyano 1-{[trans-(1S,3S)-3-(1H-imidazol-4-yl)cyclopentyl]methyl}-3-[2 (phenylsulfanyl)ethyl]guanidine ((1S,3S)-UR-RG98, 39a) was the most potent H4R agonist in this series (EC50 11 nM; H4R vs H3R, >100-fold selectivity; H1R, H2R, negligible activities), whereas the optical antipode proved to be an H4R antagonist ([(35)S]GTPgammaS assay). MD simulations confirmed differential stabilization of the active and inactive H4R state by the enantiomers. PMID- 27007612 TI - Calcinosis in juvenile dermatomyositis: frequency, risk factors and outcome. AB - The aim was to retrospectively estimate the prevalence of calcinosis in patients with juvenile dermatomyositis (JDM) and to identify risk factors associated with development of calcinosis in these patients. Retrospective chart review of 39 children diagnosed with JDM between 2004 and 2015 in a tertiary care hospital was done. Patients were divided into two groups, depending on the presence or absence of calcinosis, and the two groups were compared with respect to demographic, clinical, laboratory and therapeutic characteristics. Calcinosis developed in nine (23.1 %) patients. Delay in diagnosis and initiation of treatment, prolonged duration of disease, the presence of joint contractures and cardiac involvement were significantly associated with increased frequency of calcinosis. Six out of nine (66.7 %) patients with calcinosis received alendronate therapy, out of which four showed partial reduction in calcinosis. In one case, surgical removal of tumorous clumps was done. Calcinosis remains a common complication of JDM. We found an association between calcinosis and delay in diagnosis and initiation of treatment, prolonged duration of disease and cardiac involvement. Our study suggests that alendronate may be beneficial in management of calcinosis of JDM. PMID- 27007613 TI - Testicular microlithiasis and testicular cancer: review of the literature. AB - PURPOSE: To perform a systematic literature review to assess whether the occurrence of testicular microlithiasis (TML) in conjunction with other risk factors is associated with testicular cancer. METHODS: A systematic literature search was performed of original articles in English published 1998 to 2015. Relevant studies were selected by reading the title and abstract by two of the authors. Studies were included if TML was diagnosed by ultrasonography and a risk condition was reported. Studies were only eligible if the particular risk condition was reported in more than one article. RESULTS: In total, 282 abstracts in were identified. Based on title and abstract the eligibility was assessed and 31 studies were included. Five conditions in relation to TML and testicular cancer emerged: Down syndrome, McCune-Albright syndrome, cryptorchidism, infertility and familial disposition of testicular cancer. CONCLUSION: Data support the conclusion that TML is not an independent risk factor for testicular cancer but associated with testicular cancer through other conditions. In male infertility, TML appears to be related to an increased risk of testicular cancer possibly as part of a testicular dysgenesis syndrome. PMID- 27007614 TI - Relevance of uric acid and asymmetric dimethylarginine for modeling cardiovascular risk prediction in chronic kidney disease patients. AB - BACKGROUND: Both elevated serum uric acid and serum asymmetric dimethylarginine (ADMA) are risk factors for cardiovascular disease. We hypothesized that combined elevation of uric acid and ADMA amplifies the risk of all-cause mortality and/or cardiovascular events (CVE) in patients with chronic kidney disease (CKD). METHODS: A total of 259 patients with CKD stages 1-5 were followed up in a time to-event analysis for all-cause mortality and fatal and non-fatal CVE (including death, stroke, and myocardial infarction). Baseline measurements included serum uric acid and ADMA and endothelial function [ultrasound determined flow-mediated dilatation (FMD)]. RESULTS: As a measure of endothelial function, log FMD value was positively associated with log eGFR, but negatively associated with log ADMA and log uric acid levels. During follow-up (median 38 months), 24 (9.3 %) deaths, 90 (34.7 %) CVE, and 95 (36.7 %) deaths and CVE (composite outcome) occurred. In the univariate Cox analysis, patients with both serum uric acid and ADMA levels above the median had an increased risk of all-cause mortality, CVE, and the composite outcome (HR 5.06, 95 % CI 2.01-12.76; HR 4.75, 95 % CI 2.98-7.59; and HR 4.13, 95 % CI 2.66-6.43, respectively). However, after adjustment for renal specific risk factors (glomerular filtration rate, proteinuria, and hsCRP), this association was maintained only for CVE and the composite outcome. The addition of both biomarkers into a model with traditional and renal-specific risk factors did not increase the prediction abilities of the model for none of the three outcomes. CONCLUSION: Elevated serum uric acid and ADMA levels are associated with an increased cardiovascular risk, but their combination does not improve risk prediction. The effects are not additive, possibly because uric acid may lie in the causal pathway by which ADMA acts. PMID- 27007616 TI - In response - a descriptive analysis of aspartate and alanine aminotransferase rise and fall following acetaminophen overdose. PMID- 27007615 TI - Biochemical and Spectroscopic Characterization of a Radical S-Adenosyl-L methionine Enzyme Involved in the Formation of a Peptide Thioether Cross-Link. AB - Peptide-derived natural products are a class of metabolites that afford the producing organism a selective advantage over other organisms in their biological niche. While the polypeptide antibiotics produced by the nonribosomal polypeptide synthetases (NRPS) are the most widely recognized, the ribosomally synthesized and post-translationally modified peptides (RiPPs) are an emerging group of natural products with diverse structures and biological functions. Both the NRPS derived peptides and the RiPPs undergo extensive post-translational modifications to produce structural diversity. Here we report the first characterization of the six cysteines in forty-five (SCIFF) [Haft, D. H. and Basu M. K. (2011) J. Bacteriol. 193, 2745-2755] peptide maturase Tte1186, which is a member of the radical S-adenosyl-l-methionine (SAM) superfamily. Tte1186 catalyzes the formation of a thioether cross-link in the peptide Tte1186a encoded by an orf located upstream of the maturase, under reducing conditions in the presence of SAM. Tte1186 contains three [4Fe-4S] clusters that are indispensable for thioether cross-link formation; however, only one cluster catalyzes the reductive cleavage of SAM. Mechanistic imperatives for the reaction catalyzed by the thioether forming radical SAM maturases will be discussed. PMID- 27007617 TI - A Scalable Platform for Functional Nanomaterials via Bubble-Bursting. AB - A continuous and scalable bubbling system to generate functional nanodroplets dispersed in a continuous phase is proposed. Scaling up of this system can be achieved by simply tuning the bubbling parameters. This new and versatile system is capable of encapsulating various functional nanomaterials to form functional nanoemulsions and nanoparticles in one step. PMID- 27007618 TI - Red, yellow and green: What does it mean? How the progress test informs and supports student progress. AB - OBJECTIVES: Most medical schools using progress tests (PTs) provide feedback by utilizing a traffic-light system of green (satisfactory), yellow (borderline) and red (unsatisfactory) categories. There is little research assessing students' perceptions or usage of this feedback. Therefore this study proposed to determine the effectiveness of formative PTs at informing and supporting student progress. METHODS: A mixed methods study was performed, involving a retrospective analysis of a results database to establish the predictive validity of PT categories and 11 semi-structured interviews to explore students' perceptions of PT feedback in a graduate entry medical programme. RESULTS: Quantitative analysis revealed that students who always scored green performed better in their summative exams and graduated with a higher final degree than those who received a yellow or red category at least once. Qualitative analysis revealed that just over half of the interviewed students perceived the PT as having informed their progress. Most participants agreed that the current feedback is insufficient and doesn't guide their on-going learning. CONCLUSION: While this study demonstrated that the PT is a useful predictive tool for informing student progress, in its current format it's not fulfilling a truly formative role and supporting student progress sufficiently. PMID- 27007619 TI - Rapid Capture Next-Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B-Cell Precursor ALL. AB - Comprehensive next-generation sequencing (NGS) applications have recently identified various recurrent kinase and cytokine receptor rearrangements in Ph like B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) amenable to tyrosin kinase inhibitor treatment. For rapid diagnostics of kinase pathway aberrations in minimal residual disease (MRD) high-risk BCP-ALL, we developed a PCR-independent NGS custom enrichment capture panel targeting recurrent genomic alterations, which allows for the identification of unknown 5' fusion partner genes and precise mapping of variable genomic breakpoints. Using a standardized bioinformatics algorithm, we identified kinase and cytokine receptor rearrangements in the majority of ALL patients with high burden of postinduction MRD and enrichment of IKZF1 mutation or deletion (IKZF1(del) ). PMID- 27007621 TI - Sialic Acid-Targeted Nanovectors with Phenylboronic Acid-Grafted Polyethylenimine Robustly Enhance siRNA-Based Cancer Therapy. AB - Small interference RNA (siRNA)-based therapy holds great potential for cancer treatment. However, its clinical application remains unsatisfied due to the lack of a safe and effective RNA delivery system. Aberrantly elevated sialyation on cell membrane has been reported as an attractive target for cancer diagnosis and therapy. In this study, phenylboronic acid (PBA) was conjugated onto low molecular weight polyethylenimine (PEI1.8k) to generate amphiphilic PBA-grafted PEI1.8k (PEI-PBA) nanovector, which was designed to facilitate cancer-targeted RNA delivery through the recognition of sialic structures on a cancer cell membrane. PEI-PBA simultaneously encapsulated siRNA to form PEI-PBA/siRNA nanocomplexes with great biocompatibility, serum stability and RNase resistance. The cell culture study showed that PEI-PBA/siRNA dramatically increased siRNA uptake up to 70-90% in several cancer cell lines, which relied on the interaction between PBA and sialic acid on cell membrane. Moreover, the PEI-PBA nanovector effectively promoted the lysosome escape of siRNA, decreasing the expression of target gene Polo-like kinase 1 (PLK-1) in cancer cells. The systemic administration of PEI-PBA/PLK-1 siRNA (PEI-PBA/siPLK1) nanocomplexes not only facilitated tumor-targeted siRNA delivery but also significantly decreased PLK-1 expression in tumors, thereby robustly inducing tumor apoptosis and cell cycle arrest. Additionally, the administration of PEI-PBA/siPLK1 did not cause significant systemic toxicity or immunotoxicity. Hence, sialic acid-targeted PEI PBA could be a highly efficient and safe nanovector to improve the efficacy of cancer siRNA therapy. PMID- 27007622 TI - Luigi provasoli award recipients. PMID- 27007620 TI - A case for protein-level and site-level specificity in glycoproteomic studies of disease. AB - Abnormal glycosylation of proteins is known to be either resultant or causative of a variety of diseases. This makes glycoproteins appealing targets as potential biomarkers and focal points of molecular studies on the development and progression of human ailment. To date, a majority of efforts in disease glycoproteomics have tended to center on either determining the concentration of a given glycoprotein, or on profiling the total population of glycans released from a mixture of glycoproteins. While these approaches have demonstrated some diagnostic potential, they are inherently insensitive to the fine molecular detail which distinguishes unique and possibly disease relevant glycoforms of specific proteins. As a consequence, such analyses can be of limited sensitivity, specificity, and accuracy because they do not comprehensively consider the glycosylation status of any particular glycoprotein, or of any particular glycosylation site. Therefore, significant opportunities exist to improve glycoproteomic inquiry into disease by engaging in these studies at the level of individual glycoproteins and their exact loci of glycosylation. In this concise review, the rationale for glycoprotein and glycosylation site specificity is developed in the context of human disease glycoproteomics with an emphasis on N glycosylation. Recent examples highlighting disease-related perturbations in glycosylation will be presented, including those involving alterations in the overall glycosylation of a specific protein, alterations in the occupancy of a given glycosylation site, and alterations in the compositional heterogeneity of glycans occurring at a given glycosylation site. Each will be discussed with particular emphasis on how protein-specific and site-specific approaches can contribute to improved discrimination between glycoproteomes and glycoproteins associated with healthy and unhealthy states. PMID- 27007623 TI - Cellular interactions: lessons from the nitrogen-fixing cyanobacteria. AB - Marine nitrogen-fixing cyanobacteria play a central role in the open-ocean microbial community by providing fixed nitrogen (N) to the ocean from atmospheric dinitrogen (N2 ) gas. Once thought to be dominated by one genus of cyanobacteria, Trichodesmium, it is now clear that marine N2 -fixing cyanobacteria in the open ocean are more diverse, include several previously unknown symbionts, and are geographically more widespread than expected. The next challenge is to understand the ecological implications of this genetic and phenotypic diversity for global oceanic N cycling. One intriguing aspect of the cyanobacterial N2 fixers ecology is the range of cellular interactions they engage in, either with cells of their own species or with photosynthetic protists. From organelle-like integration with the host cell to a free-living existence, N2 -fixing cyanobacteria represent the range of types of interactions that occur among microbes in the open ocean. Here, we review what is known about the cellular interactions carried out by marine N2 fixing cyanobacteria and where future work can help. Discoveries related to the functional roles of these specialized cells in food webs and the microbial community will improve how we interpret their distribution and abundance patterns and contributions to global N and carbon (C) cycles. PMID- 27007624 TI - Green algae (Chlorophyta) and the question of freshwater symbiogenesis in the early proterozoic. PMID- 27007625 TI - Origin and early evolution of photosynthetic eukaryotes in freshwater environments: reinterpreting proterozoic paleobiology and biogeochemical processes in light of trait evolution. AB - Phylogenetic analyses were performed on concatenated data sets of 31 genes and 11,789 unambiguously alignable characters from 37 cyanobacterial and 35 chloroplast genomes. The plastid lineage emerged somewhat early in the cyanobacterial tree, at a time when Cyanobacteria were likely unicellular and restricted to freshwater ecosystems. Using relaxed molecular clocks and 22 age constraints spanning cyanobacterial and eukaryote nodes, the common ancestor to the photosynthetic eukaryotes was predicted to have also inhabited freshwater environments around the time that oxygen appeared in the atmosphere (2.0-2.3 Ga). Early diversifications within each of the three major plastid clades were also inferred to have occurred in freshwater environments, through the late Paleoproterozoic and into the middle Mesoproterozoic. The colonization of marine environments by photosynthetic eukaryotes may not have occurred until after the middle Mesoproterozoic (1.2-1.5 Ga). The evolutionary hypotheses proposed here predict that early photosynthetic eukaryotes may have never experienced the widespread anoxia or euxinia suggested to have characterized marine environments in the Paleoproterozoic to early Mesoproterozoic. It also proposes that earliest acritarchs (1.5-1.7 Ga) may have been produced by freshwater taxa. This study highlights how the early evolution of habitat preference in photosynthetic eukaryotes, along with Cyanobacteria, could have contributed to changing biogeochemical conditions on the early Earth. PMID- 27007626 TI - An analytical perspective on detection, screening, and confirmation in phycology, with particular reference to toxins and toxin-producing species. AB - Knowledge concerning the ability of microalgae to produce metabolites of interest such as toxins or high-value secondary metabolites requires exhaustive details to be supplied on how the research was conducted. These should include the microalgal species and strain characterization, the culture conditions, the cell density, and physiological state at the time of harvesting, the harvesting method, the sample pre-treatment protocol, and the subsequent instrumental analytical separation/detection system. In this comment, we discuss issues that affect algal research from an analytical chemistry perspective, particularly (i) the need to specify detection capabilities of the entire method (i.e., limits of detection or threshold detection levels), which we illustrate in relation to classification of a species or strain as being "toxin producing" or "non-toxin producing"; and (ii) the requirements that have to be satisfied to confirm a microalgal species (new or not) as a producer of a particular chemical of interest for phycologists, which again we illustrate in relation to toxins. A successful collaboration among phycologists and analytical chemists will only be achieved as a result of a synergistic collaboration between the two disciplines, with a reciprocal understanding at least at a background level. PMID- 27007627 TI - Prevailing sea surface temperatures inhibit summer reproduction of the kelp Laminaria digitata at Helgoland (North Sea). AB - The impact of abiotic factors on kelp sporophyte reproduction has rarely been investigated. Laminaria digitata (Hudson) J.V. Lamouroux is one of the few summer fertile Laminaria species worldwide and reproduction is subjected to relatively high water temperatures. We investigated the impact of prevailing summer temperatures (~18 degrees C in August) on the induction of sporangia, meiospore release, and germination at the island of Helgoland (North Sea). At Helgoland, fertile sporophytes are found between April and December with a maximum in late summer. While released meiospore numbers were constant between June and October, germination rates decreased significantly in summer. Short-term exposure of mature sori to 17 degrees C-22 degrees C induced a significantly higher meiospore release indicating enhancement of sporulation by elevated temperatures. Induction of sporangia on vegetative blade disks was not possible at 20 degrees C, and fertility was only 20% at 18 degrees C-19 degrees C, but it was 100% in cool temperatures of 1 degrees C-10 degrees C. It was shown for the first time in a kelp species that "sporogenesis" is the life-cycle process with the narrowest temperature window compared to growth or survival of the sporophyte or reproduction, growth, and survival of the gametophyte. We incorporated several parameters (induction time, fertile area, and relative fertility) into a "Reproductive efficiency index." This indicates that sporogenesis of L. digitata is a cold-adapted process with an optimum at (5)-10 degrees C. The results show that the population at Helgoland is at its reproduction limit despite the existence of other geographically more southerly located populations. PMID- 27007628 TI - Symbiont physiology and population dynamics before and during symbiont shifts in a flexible algal-cnidarian symbiosis. AB - For cnidarians that can undergo shifts in algal symbiont relative abundance, the underlying algal physiological changes that accompany these shifts are not well known. The sea anemone Anthopleura elegantissima associates with the dinoflagellate Symbiodinium muscatinei and the chlorophyte Elliptochloris marina, symbionts with very different tolerances to light and temperature. We compared the performance of these symbionts in anemones maintained in an 8-11.5 month outdoor common garden experiment with simulated intertidal conditions and three levels of shading (2, 43, and 85% ambient irradiance). Symbiont densities, mitotic indices, photophysiology and pigments were assessed at three time points during the summer, a period of high irradiance and solar heating during aerial exposure. Whereas S. muscatinei was either neutrally or positively affected by higher irradiance treatments, E. marina responded mostly negatively to high irradiance. E. marina in the 85% irradiance treatment exhibited significantly reduced Pmax and chlorophyll early in the summer, but it was not until nearly 3 months later that a shift in symbiont relative abundance toward S. muscatinei occurred, coincident with bleaching. Symbiont densities and proportions remained largely stable in all other treatments over time, and displacement of S. muscatinei by E. marina was not observed in the 2% irradiance treatment despite the potentially better performance of E. marina. While our results support the view that rapid changes in symbiont relative abundance are typically associated with symbiont physiological dysfunction and bleaching, they also show that significant temporal lags may occur between the onset of symbiont stress and shifts in symbiont relative abundances. PMID- 27007629 TI - Morphology, phylogeny, dynamics, and ichthyotoxicity of Pheopolykrikos hartmannii (Dinophyceae) isolates and blooms from New York, USA. AB - We report on morphological observations, phylogenetic analyses, bloom dynamics, and ichthyotoxicity of the common but poorly characterized dinoflagellate Pheopolykrikos hartmannii (Zimmermann) Matsuoka et Fukuyo. From 2008 to 2010 in the Forge River Estuary, NY, USA, P. hartmannii bloomed during summer and early fall, achieving densities exceeding 8,000 cells . mL(-1) and often dominating microphytoplankton communities. Large subunit (LSU) and small subunit (SSU) rDNA sequences demonstrated that NY isolates of P. hartmannii sequences were 99%-100% identical to P. hartmannii isolates from eastern US and Korea. In both the LSU and SSU rDNA phylogenies, the clades containing P. hartmannii sequences were distinct sister clades to those composed of Polykrikos schwartzii and P. kofoidii. In the LSU rDNA phylogeny, however, the clade composed of P. hartmannii and a sequence of the photosynthetic Polykrikos lebourae was well separated from the clade composed of 10 entries of Polykrikos schwartzii and P. kofoidii. In addition, a gap of ~180 bases was observed when the LSU rDNA sequences of P. hartmannii were aligned with P. schwartzii and P. kofoidii but was not observed in the alignment between P. hartmannii and P. lebourae. Using scanning electron microscopy, several morphological features previously not reported for P. hartmannii were observed: a ventral groove located in the sulcus, a deep arc-like apical concavity within the area of apical groove, scale-like vesicles, and a shallow, completely enclosed, loop-like apical groove. Resting cysts with arrow like surface spines were produced heterothallically by crossing clonal isolates and germinated single gymnoid cells. Finally, filtered and unfiltered bloom water from the Forge River and clonal cultures of P. hartmannii exhibited acute ichthyotoxicity to juvenile sheepshead minnows (Cyprinodon variegates) and aeration did not mitigate this effect, suggesting P. hartmannii is an ichthyotoxic, harmful alga. PMID- 27007630 TI - Five chemically rich species of tropical marine cyanobacteria of the genus Okeania gen. nov. (Oscillatoriales, Cyanoprokaryota). AB - An adverse consequence of applying morphology-based taxonomic systems to catalog cyanobacteria, which generally are limited in the number of available morphological characters, is a fundamental underestimation of natural biodiversity. In this study, we further dissect the polyphyletic cyanobacterial genus Lyngbya and delineate the new genus Okeania gen. nov. Okeania is a tropical and subtropical, globally distributed marine group abundant in the shallow-water benthos. Members of Okeania are of considerable ecological and biomedical importance because specimens within this group biosynthesize biologically active secondary metabolites and are known to form blooms in coastal benthic environments. Herein, we describe five species of the genus Okeania: O. hirsuta (type species of the genus), O. plumata, O. lorea, O. erythroflocculosa, and O. comitata, under the provisions of the International Code of Nomenclature for Algae, Fungi, and Plants. All five Okeania species were morphologically, phylogenetically, and chemically distinct. This investigation provides a classification system that is able to identify Okeania spp. and predict their production of bioactive secondary metabolites. PMID- 27007631 TI - Frequent recombination shapes the epidemic population structure of Planktothrix (Cyanoprokaryota) in Italian subalpine lakes. AB - The planktonic genus Planktothrix, as other cyanobacteria, shows signals of both homologous and nonhomologous recombination. However, the frequency of recombination and its effect on Planktothrix population structuring is unknown. We isolated 290 Planktothrix strains from seven neighboring lakes in the subalpine Italian region and analyzed these using multilocus sequence typing. Four of six loci analyzed were polymorphic, resulting in 20 distinct multilocus genotypes. Association indices among alleles at different loci were suggestive of an "epidemic population structure," resulting from an explosive (and temporary) dominance of one genotype against a panmictic background. ClonalFrame analyses supported this view by detecting: (i) three major clades affected by three distinct recombination events, (ii) a recombination rate about equal to the mutation rate, and (iii) the fact that recombination had an impact on introducing molecular diversity more than double the mutation rate. Furthermore, analysis of molecular variance over an annual cycle in three of seven lakes revealed that both local clonal expansion and recombination processes affected among-lake diversity. Our observations suggest that recombination affects microevolution of Planktothrix and that an epidemic structure can emerge in populations of this genus. PMID- 27007632 TI - Subcellular localization of dinoflagellate polyketide synthases and fatty acid synthase activity. AB - Dinoflagellates are prolific producers of polyketide secondary metabolites. Dinoflagellate polyketide synthases (PKSs) have sequence similarity to Type I PKSs, megasynthases that encode all catalytic domains on a single polypeptide. However, in dinoflagellate PKSs identified to date, each catalytic domain resides on a separate transcript, suggesting multiprotein complexes similar to Type II PKSs. Here, we provide evidence through coimmunoprecipitation that single-domain ketosynthase and ketoreductase proteins interact, suggesting a predicted multiprotein complex. In Karenia brevis (C.C. Davis) Gert Hansen & O. Moestrup, previously observed chloroplast localization of PKSs suggested that brevetoxin biosynthesis may take place in the chloroplast. Here, we report that PKSs are present in both cytosol and chloroplast. Furthermore, brevetoxin is not present in isolated chloroplasts, raising the question of what chloroplast-localized PKS enzymes might be doing. Antibodies to K. brevis PKSs recognize cytosolic and chloroplast proteins in Ostreopsis cf. ovata Fukuyo, and Coolia monotis Meunier, which produce different suites of polyketide toxins, suggesting that these PKSs may share common pathways. Since PKSs are closely related to fatty acid synthases (FAS), we sought to determine if fatty acid biosynthesis colocalizes with either chloroplast or cytosolic PKSs. [(3) H]acetate labeling showed fatty acids are synthesized in the cytosol, with little incorporation in chloroplasts, consistent with a Type I FAS system. However, although 29 sequences in a K. brevis expressed sequence tag database have similarity (BLASTx e-value <10(-10) ) to PKSs, no transcripts for either Type I (cytosolic) or Type II (chloroplast) FAS are present. Further characterization of the FAS complexes may help to elucidate the functions of the PKS enzymes identified in dinoflagellates. PMID- 27007633 TI - Global diversity of two widespread, colony-forming diatoms of the marine plankton, Chaetoceros socialis (syn. C. radians) and Chaetoceros gelidus sp. nov. AB - Marine phytoplankton samples containing diatoms of the Chaetoceros socialis group were collected from Thailand, China, Denmark, and Greenland, and cells were isolated into culture for light and electron microscopy and DNA sequencing of D1 D3 of the LSU rDNA. Species of this lineage are characterized by three short and one long setae extending from each cell, the long setae from several cells joining into a common center to form large colonies, which are sometimes visible with the naked eye. Phylogenetic analyses including sequences from other parts of the world revealed segregation into three groups. Most sequences fell into two large clades, one comprising material from cold waters, whereas the other contained material from warmer waters. Strain CCMP 172 from the Strait of Georgia, Washington State, USA, formed a separate group. The warm-water species included Chinese and Thai material and therefore probably also material from the type locality of C. socialis, Hong Kong. It is characterized by all setae being covered by spines and the setae extending from the valve at some distance from the margin. In the resting spores, both valves are ornamented with spines. The cold-water material is characterized by three spiny and one mostly smooth long setae, and the setae extend from the valve near the margin. Both valves of the resting spore are smooth. This material is described as C. gelidus sp. nov. C. radians, described from the Baltic in 1894, is considered a synonym of C. socialis. CCMP172 is in many ways intermediate and probably constitutes a separate species. The published evidence on this globally distributed and sometimes bloom-forming group of species indicates higher species diversity than presently thought. PMID- 27007634 TI - Characterization of freshwater benthic biofilm-forming Hydrocoryne (Cyanobacteria) isolates from Antarctica. AB - The aims of this work were to study cyanobacterial isolates resembling the genus Hydrocoryne using a combination of morphology and phylogeny of 16S rRNA and nifH sequences and to investigate genes involved in cyanotoxin and protease inhibitor production. Four new cyanobacterial strains, isolated from biofilm samples collected from King George Island, Antarctica, were studied. In terms of morphology, these new strains share traits similar to true Anabaena morphotypes (benthic ones), whereas phylogenetic analysis of their 16S rRNA gene sequences grouped them with the sequence of the type species Hydrocoryne spongiosa (H. Schwabe ex Bornet and Flahault 1886-1888), but not with sequences of the type species from the genus Anabaena. This cluster is the sister group of Anabaena morphotypes isolated only from the Gulf of Finland. In addition, this cluster is related to two other clusters formed by sequences of Anabaena isolated from different sites. Partial nifH genes were sequenced from two strains and the phylogenetic tree revealed that the Antarctic nifH sequences clustered with sequences from Anabaena. Furthermore, two strains were tested, using PCR with specific primers, for the presence of genes involved in cyanotoxins (microcystin and saxitoxin) and protease inhibitor (aeruginosin, and cyanopeptolin). Only cyanopeptolin was amplified using PCR. These four Hydrocoryne strains are the first to be isolated and sequenced from Antarctica, which improves our knowledge on this poorly defined cyanobacterial genus. PMID- 27007635 TI - Molecular and morphological criteria for revision of the genus Microcoleus (Oscillatoriales, Cyanobacteria). AB - Ninety-two strains of Microcoleus vaginatus (=nomenclatural-type species of the genus Microcoleus Desmazieres ex Gomont) and Phormidium autumnale Trevisan ex Gomont from a wide diversity of regions and biotopes were examined using a combination of morphological and molecular methods. Phylogenies based on the 16S rDNA and 16S-23S ITS (partial) demonstrated that the 92 strains, together with a number of strains in GenBank, were members of a highly supported monophyletic clade of strains (Bayesian posterior probability = 1.0) distant from the species cluster containing the generitype of Phormidium. Similarity of the 16S rRNA gene exceeded 95.5% among all members of the Microcoleus clade, but was less than 95% between any Microcoleus strains and species outside of the clade (e.g., Phormidium sensu stricto). These findings, which are in agreement with earlier studies on these taxa, necessitate the revision of Microcoleus to include P. autumnale. Furthermore, the cluster of Phormidium species in the P. autumnale group (known as Group VII) must be moved into Microcoleus as well, and these nomenclatural transfers are included in this study. The main diacritical characters defining Microcoleus are related to the cytomorphology of trichomes, including: narrowed trichome ends, calyptra, cells shorter than wide up to more or less isodiametric, and facultative presence of sheaths. The majority of species are 4-10 MUm in diameter. The possession of multiple trichomes in a common sheath is present facultatively in many but not all species. PMID- 27007636 TI - Polyamine effects on protein disulfide isomerase expression and implications for hypersalinity stress in the marine alga Ulva lactuca Linnaeus(1). AB - Full-length protein disulfide isomerase (UfPDI) cDNA was cloned from the intertidal macroalga Ulva lactuca Linnaeus. Modulation of UfPDI expression by stresses and polyamines (PA) was studied. UfPDI transcription and enzyme activity were increased by hypersalinity (90) or high light illumination (1,200 MUmol photons . m(-2) . s(-1) ), decreased by the addition of 100 MUM CuSO4 . An exposure to a salinity of 90 decreased PA contents. Treating with PA biosynthetic inhibitors, D-arginine (D-Arg) or alpha-methyl ornithine (alpha-MO), led to a further decrease and also inhibited UfPDI expression and recovery of the growth rate. These results suggest that PAs are required to activate UfPDI expression with hypersalinity, even PA contents are decreased at a salinity of 90. The induction of UfPDI expression by hypersalinity of 90 and tolerance to hypersalinity could be enhanced if internal PA contents rise. Sung et al. (2011b) showed that PA contents could be increased by pretreating with putrescine (Put, 1 mM), spermidine (Spd, 1 mM), or spermine (Spm, 1 mM) at a salinity of 30. Therefore, PA pretreatment effect on UfPDI expression was examined. Pretreatment with Spd and Spm, but not with Put, enhanced UfPDI expression after transferred to a salinity of 90 and restored the growth rate. In conclusion, induction of UfPDI expression by Spd or Spm before exposure to hypersaline conditions and continuous up-regulation after hypersalinity exposure are required for the acquisition of hypersalinity tolerance in the intertidal green macroalga U. lactuca. PMID- 27007637 TI - The genus Pseudo-nitzschia (Bacillariophyceae) in a temperate estuary with description of two new species: Pseudo-nitzschia plurisecta sp. nov. and Pseudo nitzschia abrensis sp. nov. AB - The genus Pseudo-nitzschia contains potentially toxic species of problematic taxonomy, making it one of the most intensively studied diatom genera. The study of 35 clonal strains isolated from the Bilbao estuary, an area that experiences recurrent blooms of Pseudo-nitzschia, revealed the presence of two new species, P. abrensis and P. plurisecta, differing from their congeners in both morphology and gene sequence. The morphological features were analyzed by LM and EM, whereas molecular analyses were based on the internal transcribed spacer (ITS) and large subunit (LSU) regions of the rDNA. P. plurisecta appears closely related to P. cuspidata/P. pseudodelicatissima in the phylogenetic tree, whereas P. abrensis forms a moderately supported clade with P. heimii/P. subpacifica and P. caciantha/P. circumpora. Comparison of the secondary structure of ITS2 regions reveals marked differences in the most highly conserved regions among related taxa. Morphologically, the new species differ from their closest congeners in the arrangement of the poroid sectors and the density of valve striae and fibulae. The two species share similar pigment composition, and belong to the group of Pseudo-nitzschia species containing only chlorophyll c2 and c3 . PMID- 27007638 TI - Revisiting Ross and Sims (1971): toward a molecular phylogeny of the Biddulphiaceae and Eupodiscaceae (Bacillariophyceae). AB - The ocellate and pseudocellate diatoms in the Eupodiscaceae and Biddulphiaceae (respectively) are common inhabitants of the marine littoral (and plankton zone) with a rich fossil history making them important components of marine stratigraphic studies and good candidates for molecular dating work. These diatoms are important for un-derstanding the phylogeny of the diatoms as a whole, as molecular phylogenies have blurred the traditional distinction between the pennate and multipolar non-pennate diatoms. However, the convoluted taxonomic history of these groups has the potential to disrupt both stratigraphic and molecular dating studies. Although efforts have been made to examine frustule morphology of several ocellate and pseudocellate diatoms and develop a morphological scheme to define genera, very little work has been done to determine how these groups are interrelated. In this study, we use nuclear and chloroplast molecular markers to construct a phylogeny of a diverse sampling of Eupodiscaceae and Biddulphiaceae taxa. The ocellus-bearing taxa (Eupodiscaceae) are monophyletic, and thus the ocellus may be a useful character in delimiting the Eupodiscaceae, the Biddulphiaceae are polyphyletic and scattered across a number of lineages of multipolar non-pennate diatoms. Hypothesis testing aimed at assessing the likeliness of several morphology based hypotheses against the molecular data highlights uncertainty in both types of data. We present evidence that there are monophyletic genera within both the Biddulphiaceae and Eupodiscaceae, and recommend the taxa within the Odontella mobilensis/sinensis/regia clade be transferred to a new genus: Trieres Ashworth & Theriot. PMID- 27007639 TI - Continuous hydrogen peroxide production by organic buffers in phytoplankton culture media. AB - We investigated the production of hydrogen peroxide (HOOH) in illuminated seawater media containing a variety of zwitterionic buffers. Production rates varied extensively among buffers, with 4-(2-hydroxyethyl)1 piperazineethanesulfonic acid (HEPES) highest and N-Tris(hydroxymethyl)methyl-3 aminopropanesulfonic acid (TAPS) among the lowest. The rate of HOOH accumulation was remarkably consistent over many days, and increased linearly with buffer concentration, natural seawater concentration, and light level. Concentrations of HEPES commonly used in culture media (1-10 mM) generated enough HOOH to kill the axenic Prochlorococcus strain VOL1 during growth in enriched seawater media at lower, environmentally realistic cell concentrations and/or under high light exposure. We also demonstrated that HEPES can be used experimentally to study the biological effects of chronic exposure to sublethal levels of HOOH such as may be experienced by light-exposed microorganisms. PMID- 27007640 TI - Integrated mental health atlas of the Western Sydney Local Health District: gaps and recommendations. AB - Objective Australian mental health care remains hospital centric and fragmented; it is riddled with gaps and does little to promote recovery. Reform must be built on better knowledge of the shape of existing services. Mental health atlases are an essential part of this knowledge base, enabling comparison with other regions and jurisdictions, but must be based on a rigorous classification of services. The main aim of this study is to create an integrated mental health atlas of the Western Sydney LHD in order to help decision makers to better plan informed by local evidence. Methods The standard classification system, namely the Description and Evaluation of Services and Directories in Europe for Long-term Care model, was used to describe and classify adult mental health services in the Western Sydney Local Health District (LHD). This information provided the foundation for accessibility maps and the analysis of the provision of care for people with a lived experience of mental illness in Western Sydney LHD. All this data was used to create the Integrated Mental Health Atlas of Western Sydney LHD. Results The atlas identified four major gaps in mental health care in Western Sydney LHD: (1) a lack of acute and sub-acute community residential care; (2) an absence of services providing acute day care and non-acute day care; (3) low availability of specific employment services for people with a lived experience of mental ill-health; and (4) a lack of comprehensive data on the availability of supported housing. Conclusions The integrated mental health atlas of the Western Sydney LHD provides a tool for evidence-informed planning and critical analysis of the pattern of adult mental health care. What is known about the topic? Several reports have highlighted that the Australian mental health system is hospital based and fragmented. However, this knowledge has had little effect on actually changing the system. What does this paper add? This paper provides a critical analysis of the pattern of adult mental health care provided within the boundaries of the Western Sydney LHD using a standard, internationally validated tool to describe and classify the services. This provides a good picture of the availability of adult mental health care at the local level that was hitherto lacking. What are the implications for practitioners? The data presented herein provide a better understanding of the context in which mental health practitioners work. Managers and planners of services providing care for people with a lived experience of mental illness can use the information herein for better planning informed by local evidence. PMID- 27007643 TI - Risk of Use of Antidepressants Among Children and Young Adults Exposed to the Death of a Parent. AB - BACKGROUND: Insight into how early parental death impact psychological well-being in children and young adults is important to developing suitable supportive care. The purpose of this study was to investigate the association between early parental death before the child reaches age 30 years and subsequent use of antidepressants. METHODS: Our nationwide population-based cohort of persons born in Denmark in 1970-1990 with follow-up in the period 1997-2009 comprised 1,124,215 persons, of whom 71,380 were bereaved. We used Poisson models to assess rate ratios for use of antidepressants according to early parental death. RESULTS: Follow-up yielded 13,074,146 person-years at risk during which 93,347 persons used antidepressants. Persons who experienced early parental death had an increased risk for use of antidepressants (men: risk ratio, 1.21; 95% confidence interval, 1.16, 1.26; women: 1.23; 95% confidence interval, 1.19, 1.27). We observed stronger associations for women whose parent died by suicide than from other causes, who lost their mother rather than their father, and who lost a parent early rather than later. The increased risk remained more than 2 years from the loss. CONCLUSIONS: Persons who lost a parent had an increased risk of use of antidepressants. Subgroups with particularly increased risk, included women, who were bereaved by suicides, who experienced loss of a mother, and who were bereaved when young. The risk of initiating antidepressant use was increased both immediately after the loss and later. Our results support that early parental death severely affects children's psychological well-being. PMID- 27007642 TI - Sensitivity to Excluding Treatments in Network Meta-analysis. AB - Network meta-analysis of randomized controlled trials is increasingly used to combine both direct evidence comparing treatments within trials and indirect evidence comparing treatments across different trials. When the outcome is binary, the commonly used contrast-based network meta-analysis methods focus on relative treatment effects such as odds ratios comparing two treatments. As shown in a recent report, when using contrast-based network meta-analysis, the impact of excluding a treatment in the network can be substantial, suggesting a methodological limitation. In addition, relative treatment effects are sometimes not sufficient for patients to make decisions. For example, it can be challenging for patients to trade off efficacy and safety for two drugs if they only know the relative effects, not the absolute effects. A recently proposed arm-based network meta-analysis, based on a missing-data framework, provides an alternative approach. It focuses on estimating population-averaged treatment-specific absolute effects. This article examines the influence of treatment exclusion empirically using 14 published network meta-analyses, for both arm- and contrast based approaches. The difference between these two approaches is substantial, and it is almost entirely due to single-arm trials. When a treatment is removed from a contrast-based network meta-analysis, it is necessary to exclude other treatments in two-arm studies that investigated the excluded treatment; such exclusions are not necessary in arm-based network meta-analysis, leading to substantial gain in performance. PMID- 27007641 TI - A structural comparison of Listeria monocytogenes protein chaperones PrsA1 and PrsA2 reveals molecular features required for virulence. AB - Listeria monocytogenes is a Gram-positive environmental bacterium that lives within soil but transitions into a pathogen upon contact with a mammalian host. The transition of L. monocytogenes from soil dweller to cytosolic pathogen is dependent upon secreted virulence factors that mediate cell invasion and intracellular growth. PrsA1 and PrsA2 are secreted bacterial lipoprotein chaperones that contribute to the folding of proteins translocated across the bacterial membrane; PrsA2 is required for L. monocytogenes virulence, whereas the function of PrsA1 remains to be determined. We have solved an X-ray crystal structure of PrsA1 and have used this model to guide comparison structure-based mutagenesis studies with PrsA2. Targeted mutagenesis of PrsA2 demonstrates that oligomerization of PrsA2 as well as molecular features of the foldase domain are required for protein secretion and virulence, whereas a functional role was uncovered for PrsA1 in bacterial resistance to alcohol. Interestingly, PrsA2 membrane localization is not required for all PrsA2-dependent activities, suggesting that the lipoprotein retains function when released from the bacterial cell. PrsA chaperones are thus multifaceted proteins with distinct domains adapted to accommodate the functional needs of a diverse array of secreted substrates. PMID- 27007644 TI - Low-dose Aspirin, Nonsteroidal Anti-inflammatory Drugs, Selective COX-2 Inhibitors and Breast Cancer Recurrence. AB - BACKGROUND: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors may improve outcomes in breast cancer patients. We investigated the association of aspirin, NSAIDs, and use of selective COX-2 inhibitors with breast cancer recurrence. METHODS: We identified incident stage I-III Danish breast cancer patients in the Danish Breast Cancer Cooperative Group registry, who were diagnosed during 1996-2008. Prescriptions for aspirin (>99% low-dose aspirin), NSAIDs, and selective COX-2 inhibitors were ascertained from the National Prescription Registry. Follow-up began on the date of breast cancer primary surgery and continued until the first of recurrence, death, emigration, or 1 January 2013. We used Cox regression models to compute hazard ratios (HR) and corresponding 95% confidence intervals (95% CI) associating prescriptions with recurrence, adjusting for confounders. RESULTS: We identified 34,188 breast cancer patients with 233,130 person-years of follow-up. Median follow-up was 7.1 years; 5,325 patients developed recurrent disease. Use of aspirin, NSAIDs, or selective COX-2 inhibitors was not associated with the rate of recurrence (HRadjusted aspirin = 1.0, 95% CI = 0.90, 1.1; NSAIDs = 0.99, 95% CI = 0.92, 1.1; selective COX-2 inhibitors = 1.1, 95% CI = 0.98, 1.2), relative to nonuse. Prediagnostic use of the exposure drugs was associated with reduced recurrence rates (HRaspirin = 0.92, 95% CI = 0.82, 1.0; HRNSAIDs = 0.86, 95% CI = 0.81, 0.91; HRsCOX-2inhibitors = 0.88, 95% CI = 0.83, 0.95). CONCLUSIONS: This prospective cohort study suggests that post diagnostic prescriptions for aspirin, NSAIDs, and selective COX-2 inhibitors have little or no association with the rate of breast cancer recurrence. Prediagnostic use of the drugs was, however, associated with a reduced rate of breast cancer recurrence. PMID- 27007645 TI - Continuous measurement of enzymatic kinetics in droplet flow for point-of-care monitoring. AB - Droplet microfluidics is ideally suited to continuous biochemical analysis, requiring low sample volumes and offering high temporal resolution. Many biochemical assays are based on enzymatic reactions, the kinetics of which can be obtained by probing droplets at multiple points over time. Here we present a miniaturised multi-detector flow cell to analyse enzyme kinetics in droplets, with an example application of continuous glucose measurement. Reaction rates and Michaelis-Menten kinetics can be quantified for each individual droplet and unknown glucose concentrations can be accurately determined (errors <5%). Droplets can be probed continuously giving short sample-to-result time (~30 s) measurement. In contrast to previous reports of multipoint droplet measurement (all of which used bulky microscope-based setups) the flow cell presented here has a small footprint and uses low-powered, low-cost components, making it ideally suited for use in field-deployable devices. PMID- 27007646 TI - Controversies Regarding the Psychometric Properties of the Brief COPE: The Case of the Brazilian-Portuguese Version "COPE Breve". AB - The Brief Coping Orientation to Problems Experienced (COPE) inventory investigates the different ways in which people respond to stressful situations. Knowledge is lacking regarding the coping strategies and styles of people in developing countries, including Brazil. This study aimed to adapt and validate the Brief COPE to Brazilian Portuguese (named COPE Breve) by focusing on dispositional coping. For the cross-cultural adaptation, the original Brief COPE in English (28 items grouped into 14 subscales) was adapted according to a universalistic approach, following these steps: translation, synthesis, back translation, analysis by an expert panel, and pretest with 30 participants. Then, 237 adults from the community health service responded to the COPE Breve. Psychometric analyses included reliability and exploratory factor analysis. Most of the 14 subscales from the original Brief COPE exhibited problems related to internal consistency. A Velicer's minimum average partial test (MAP) was performed and pointed out 3 factors. Exploratory factor analysis produced a revised 20-item version with a 3-factor solution: religion and positive reframing, distraction and external support. The psychometric properties of the COPE Breve with three factors were appropriate. Limitations of this study as well as suggestions for future studies are presented. The COPE Breve should be used in Brazilian clinics and investigations, but divergences in its psychometrics should be further explored in other contexts. PMID- 27007647 TI - OFF-ON-OFF fluorescent response of N,N,N',N'-tetrakis(1-isoquinolylmethyl)-2 hydroxy-1,3-propanediamine (1-isoHTQHPN) toward Zn(2.). AB - An isoquinoline-based ligand, N,N,N',N'-tetrakis(1-isoquinolylmethyl)-2-hydroxy 1,3-propanediamine (1-isoHTQHPN), exhibits a fluorescence increase at 475 nm upon addition of 1 equiv. of Zn(2+) (IZn/I0 = 12, phiZn = 0.023). This fluorescence enhancement turns and then decreases sharply after the addition of more than 1 equiv. of Zn(2+) reaching a constant minimum intensity with more than 2 equiv. of Zn(2+). In contrast, the fluorescence intensity at 353 nm continues to increase until the signal saturates at ca. 5 equiv. of Zn(2+). This observation can be explained by the formation of a fluorescent mononuclear complex ([Zn(1 isoHTQHPN)](2+)) followed by a non-fluorescent dinuclear complex ([Zn2(1 isoTQHPN)](3+)) at 475 nm during the titration of 1-isoHTQHPN with Zn(2+). Both the mono- and dinuclear complexes were characterized by UV-vis, fluorescence, (1)H NMR, ESI-MS, X-ray crystallography and TDDFT calculations. The fluorescence enhancement at 475 nm is Zn(2+)-specific; Cd(2+) induces a much smaller emission increase (ICd/I0 = 3.7, ICd/IZn = 31%). The Zn(2+)/Cd(2+) selectivity of the fluorescent response correlates with the difference in excimer-forming ability derived from the Cd-Nisoquinoline and Zn-Nisoquinoline bond distances. PMID- 27007648 TI - World TB Day 2016: an interview with leading experts in tuberculosis research. AB - In this interview, we talk to leading tuberculosis (TB) experts from University College London and the London School of Hygiene and Tropical Medicine about the current challenges in TB research. The video of this interview is available here: https://www.youtube.com/watch?v=75Die7MQBec&feature=youtu.be . The video can also be downloaded via Additional file 1. PMID- 27007649 TI - Biomechanical Comparison of Locking Compression Plate versus Positive Profile Pins and Polymethylmethacrylate for Stabilization of the Canine Lumbar Vertebrae. AB - OBJECTIVE: To compare the stiffness, angular deformation, and mode of failure of lumbar vertebral column constructs stabilized with bilateral pins and polymethylmethacrylate (Pin-PMMA) or with a unilateral (left) locking compression plate (LCP) with monocortical screws. STUDY DESIGN: Ex vivo biomechanical, non randomized. SAMPLES: Cadaveric canine thoracolumbar specimens (n=16). METHODS: Thoracolumbar (T13-L3) vertebral specimens had the L1-L2 vertebral motion unit stabilized with either Pin-PMMA or LCP. Stiffness in flexion, extension, and right and left lateral bending after nondestructive testing were compared between intact (pretreated) specimens and Pin-PMMA, and LCP constructs. The Pin-PMMA and LCP constructs were then tested to failure in flexion and left lateral bending. RESULTS: Both the Pin-PMMA and LCP constructs had reduced range of motion at the stabilized L1-L2 vertebral motion unit compared to intact specimens. The Pin-PMMA constructs had less range of motion for the flexion elastic zone than LCP constructs. The Pin-PMMA constructs were stiffer than intact specimens in flexion, extension, and lateral bending, and stiffer than LCP constructs in flexion and left lateral bending. The Pin-PMMA constructs had less angular deformation at construct yield and lower residual deformation at L1-L2 than LCP constructs after destructive testing to failure in flexion. The Pin-PMMA constructs were stiffer, stronger, and had less deformation at yield than LCP constructs after destructive testing to failure in lateral bending. Most constructs failed distant to the implant and fixation site. CONCLUSIONS: Pin-PMMA constructs had greater lumbar vertebral stiffness and reduced ROM than LCP constructs; however, both Pin-PMMA and LCP constructs were stronger than intact specimens. PMID- 27007650 TI - Comparison of totally tubeless percutaneous nephrolithotomy and standard percutaneous nephrolithotomy for kidney stones: a randomized, clinical trial. AB - This study aimed to compare the totally tubeless percutaneous nephrolithotomy and standard percutaneous nephrolithotomy techniques regarding their rates of success and complications in patients with kidney stones. Patients were randomly assigned to two groups. Forty-four patients (24 men; mean age: 50.40+/-2.02 years) received totally tubeless percutaneous nephrolithotomy (PCNL; no nephrostomy catheter or ureteral catheter after PCNL) and 40 patients (18 men; mean age: 49.95 +/- 13.38 years) underwent standard PCNL (a nephrostomy catheter and ureteral catheter were used after PCNL). All surgeries were performed by one surgeon. Postoperative changes in hemoglobin, the blood transfusion rate, changes in creatinine levels, operation time, analgesic need, hospitalization time, and complication rate were compared between the groups. No significant differences were observed in age, gender, stone size, and surgery side between the groups (P<0.05). The operation time was significantly lower in the totally tubeless PCNL group than in the standard PCNL group (P=0.005). Pethidine requirements were significantly higher in the standard PCNL group than the totally tubeless PCNL group (P=0.007). Hospitalization time was significantly higher in the standard PCNL group than in the totally tubeless PCNL group (P<0.0001). The complication rate was 15% in the standard PCNL group and 9.1% in the totally tubeless PCNL group (P=0.73). The totally tubeless PCNL technique is safe and effective, even for patients with staghorn stones. This technique is associated with decreased pain, analgesic needs, and operative and hospitalization time. We believe that a normal peristaltic ureter is the best drainage tube. PMID- 27007651 TI - Cytokine profile and lymphocyte subsets in type 2 diabetes. AB - Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6+/-6.3 years old) with T2D and 20 nonsmoking men (49.4+/-7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL 17, tumor necrosis factor-alpha, and interferon-gamma cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-gamma producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease. PMID- 27007652 TI - Transplantation and survival of mouse inner ear progenitor/stem cells in the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results. AB - In mammals, damage to sensory receptor cells (hair cells) of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs) are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350 g) were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4) received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4) received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy. PMID- 27007653 TI - Rescuing axons from degeneration does not affect retinal ganglion cell death. AB - After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD), an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs) after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18) treated with an exogenous calpain inhibitor (20 mM) administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05) and an increase in the number of preserved fibers (P<0.05) 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage. PMID- 27007654 TI - Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence. AB - Meningiomas are common, usually benign tumors of the central nervous system that have a high rate of post-surgical recurrence or regrowth. We determined expression of the proteins merlin, NDRG2, ERBB2, and c-MYC in meningiomas using immunohistochemistry and assessed relationships between protein expression and gender, age, tumor grade, and recurrence or regrowth. The study sample comprised 60 patients, (44 women and 16 men) with a mean age of 53.2 +/- 12.7 years. Tumors were classified as grade I (n=48) or grades II and III (n=12). Expression of merlin, NDRG2, ERBB2, and c-MYC was not significantly different statistically with relation to gender, age, or meningioma recurrence or regrowth. Merlin was expressed in 100% of the cases. No statistically significant difference between tumor grade and recurrence or regrowth was identified. Statistically significant differences were identified between the mean age of patients with grade I (54.83 +/- 11.60) and grades II and III (46.58 +/- 15.08) meningiomas (P=0.043), between strong c-MYC expression and grades II and III (P<0.001), and between partial surgical resection and tumor recurrence or regrowth (P<0.001). These findings reveal the lower mean age among grades II and III meningioma patients than grade I patients, the influence of the protein merlin on tumorigenesis, the association of c-MYC with aggressive meningiomas, and that partial surgical resection is associated with tumor recurrence or regrowth. PMID- 27007655 TI - HLA-DR3 antigen in the resistance to idiopathic dilated cardiomyopathy. AB - Idiopathic dilated cardiomyopathy (IDC) has been hypothesized as a multifactorial disorder initiated by an environment trigger in individuals with predisposing human leukocyte antigen (HLA) alleles. Published data on the association between HLA-DR3 antigen and IDC risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Studies were identified by searching the PUBMED and Embase database (starting from June 2015). A total of 19 case-control studies including 1378 cases and 10383 controls provided data on the association between HLA-DR3 antigen and genetic susceptibility to IDC. Overall, significantly decreased frequency of HLA-DR3 allele (OR=0.72; 95%CI=0.58-0.90; P=0.004) was found in patients with IDC compared with controls. When stratified by myocardial biopsy or non-biopsy cases, statistically decreased risk was found for IDC in myocardial biopsy cases (OR=0.69; 95%CI=0.57-0.84; P=0.0003). In the subgroup analysis by ethnicity, borderline statistically significantly decreased risk was found among Europeans from 12 case-control studies (OR=0.76; 95%CI=0.58-1.00; P=0.05). In conclusion, our results suggest that individuals with HLA-DR3 antigen may have a protective effect against IDC. PMID- 27007656 TI - Multiple facets of HIV-associated renal disease. AB - HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count >= 200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 >= 200 cells/mm3 had eGFR >60 mL.min-1.(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count >= 200 cells/mm3 was associated with better renal function after 2 years of follow-up. PMID- 27007657 TI - Enhanced production and organic solvent stability of a protease from Brevibacillus laterosporus strain PAP04. AB - A bacterial strain (PAP04) isolated from cattle farm soil was shown to produce an extracellular, solvent-stable protease. Sequence analysis using 16S rRNA showed that this strain was highly homologous (99%) to Brevibacillus laterosporus. Growth conditions that optimize protease production in this strain were determined as maltose (carbon source), skim milk (nitrogen source), pH 7.0, 40 degrees C temperature, and 48 h incubation. Overall, conditions were optimized to yield a 5.91-fold higher production of protease compared to standard conditions. Furthermore, the stability of the enzyme in organic solvents was assessed by incubation for 2 weeks in solutions containing 50% concentration of various organic solvents. The enzyme retained activity in all tested solvents except ethanol; however, the protease activity was stimulated in benzene (74%) followed by acetone (63%) and chloroform (54.8%). In addition, the plate assay and zymography results also confirmed the stability of the PAP04 protease in various organic solvents. The organic solvent stability of this protease at high (50%) concentrations of solvents makes it an alternative catalyst for peptide synthesis in non-aqueous media. PMID- 27007658 TI - Distribution of Pyrethroid Resistant Populations of Triatoma infestans in the Southern Cone of South America. AB - BACKGROUND: A number of studies published during the last 15 years showed the occurrence of insecticide resistance in Triatoma infestans populations. The different toxicological profiles and mechanisms of resistance to insecticides is due to a genetic base and environmental factors, being the insecticide selective pressure the best studied among the last factors. The studies on insecticide resistance on T. infestans did not consider the effect of environmental factors that may influence the distribution of resistance to pyrethroid insecticides. To fill this knowledge gap, the present study aims at studying the association between the spatial distribution of pyrethroid resistant populations of T. infestans and environmental variables. METHODOLOGY/PRINCIPAL FINDINGS: A total of 24 articles reporting on studies that evaluated the susceptibility to pyrethroids of 222 field-collected T. infestans populations were compiled. The relationship between resistance occurrence (according to different criteria) with environmental variables was studied using a generalized linear model. The lethal dose that kills 50% of the evaluated population (LD50) showed a strong linear relationship with the corresponding resistance ratio (RR50). The statistical descriptive analysis of showed that the frequency distribution of the Log (LD50) is bimodal, suggesting the existence of two statistical groups. A significant model including 5 environmental variables shows the geographic distribution of high and low LD50 groups with a particular concentration of the highest LD50 populations over the region identified as the putative center of dispersion of T. infestans. CONCLUSIONS/SIGNIFICANCE: The occurrence of these two groups concentrated over a particular region that coincides with the area where populations of the intermediate cytogenetic group were found might reflect the spatial heterogeneity of the genetic variability of T. infestans, that seems to be the cause of the insecticide resistance in the area, even on sylvatic populations of T. infestans, never before exposed to pyrethroid insecticides, representing natural and wild toxicological phenotypes. The strong linear relationship found between LD50 and RR50 suggest RR50 might not be the best indicator of insecticide resistance in triatomines. PMID- 27007660 TI - Predictive biomarkers in the treatment of HER2-positive breast cancer: an ongoing challenge. AB - The transmembrane tyrosine kinase receptor HER2 is overexpressed in 20% of invasive breast cancers and is associated with more aggressive disease. Until the advent of targeted agents, HER2 was associated with worse outcome. Trastuzumab, a recombinant humanized anti-HER2 monoclonal antibody, combined with chemotherapy improves disease-free and overall survival in both primary and metastatic tumors and represents a foundation of care for patients with HER2-positive breast cancers. However, a sizeable number of patients do not respond to this reagent, indicating the need for a biomarker able to recognize resistant tumors. Here, we review various studies on mechanisms of action and resistance to trastuzumab that have proven relevant in understanding how tumor care can be tailored to all HER2 positive patients. PMID- 27007659 TI - Whole Exome Sequencing in Patients with the Cuticular Drusen Subtype of Age Related Macular Degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly people worldwide. Cuticular drusen (CD) is a clinical subtype of AMD, which typically displays an earlier age at onset, and has a strong genetic component. Genetic studies support a role for rare sequence variants in CD susceptibility, and rare sequence variants in the CFH gene have been identified in 8.8% of CD cases. To further explore the role of rare variants in CD, we performed whole exome sequencing (WES) in 14 affected members of six families and 12 sporadic cases with CD. We detected rare sequence variants in CFH and FBLN5, which previously were shown to harbor rare variants in patients with CD. In addition, we detected heterozygous rare sequence variants in several genes encoding components of the extracellular matrix (ECM), including FBLN1, FBLN3/EFEMP1, FBLN5, FBLN6/HMCN1, FBN2, and COL15A1. Two rare pathogenic variants were identified in the COL15A1 gene: one in a sporadic case and another was found to segregate in a family with six affected individuals with CD. In addition, two rare pathogenic variants were identified in the FGL1 gene in three unrelated CD cases. These findings suggest that alterations in the ECM and in the coagulation pathway may play a role in the pathogenesis of CD. The identified candidate genes require further analyses in larger cohorts to confirm their role in the CD subtype of AMD. No evidence was found of rare sequence variants in a single gene that segregate with CD in the six families, suggesting that the disease is genetically heterogeneous. PMID- 27007661 TI - Werner Forssmann - A Nobel Prize Winner and His Political Attitude before and after 1945. AB - PURPOSE: In 1956, the Nobel Prize in Physiology or Medicine was awarded jointly to Werner Forssmann, Andre Frederic Cournand and Dickinson W. Richards for their development of cardiac catheterization. Forssmann performed a self-experiment in 1929 by inserting a urethral catheter into his right ventricular cavity via his antecubital vein. Despite his popularity as one of the first German Nobel Laureates after 1945, little is known about Forssmann personally. This contribution aims to close this gap regarding the Nazi period and early post-war Germany. METHODS: Primary historical sources from Forssmann's private archive were examined, evaluated and interpreted for the first time. Additionally, a comparative analysis based on further archival and secondary sources was performed. RESULTS: Werner Forssmann joined the Nazi Party, the Sturmabteilung (Stormtroopers, SA) and the Nationalsozialistischer Deutscher Arztebund (Nazi Doctors' Association) in 1932, a year before Hitler's assumption of power. In his autobiography, Forssmann referred to the political situation in passing. However, he expressed his personal thoughts in private letters which he wrote as a medical officer during the war. After World War II, Forssmann underwent denazification and was banned from practicing medicine for 3 years. He did not seem to be averse to Hitler's politics and in some ways expressed his approval. However, correspondence from the 1960s with 2 Jewish colleagues reveals that Forssmann may have changed his attitude toward National Socialism later. CONCLUSION: Werner Forssmann's political attitudes during the Third Reich and in the post-war era can be characterized as early agreement that gradually changed to a more critical distance to Nazi ideology. In this respect, Forssmann appears to be quite a typical example of a larger proportion of German medical doctors during these eras. PMID- 27007662 TI - Risk of bradykinin B2 receptor -58T/C gene polymorphism on hypertension: A meta analysis. AB - The risk of bradykinin B2 receptor (BDKRB2)-58T/C gene polymorphism on hypertension remains controversial. The Cochrane Library, Chinese Biomedical Database, EBSCO, Embase, ISI, MEDLINE, and PubMed were retrieved, and relevant articles were selected. The significant association between BDKRB2 -58T/C gene polymorphism and risk of hypertension were found under C-allele comparison (odds ratio (OR): 1.22, 95% confidential intervals (CI): 1.05-1.42), recessive model (OR: 1.32, 95% CI: 1.07-1.64), dominant model (OR: 0.74, 95% CI: 0.58-0.94), homozygote model (OR: 1.66, 95% CI: 1.11-2.47) and heterozygote model (OR: 1.23, 95% CI: 1.06-1.43). The magnitude of the association between the BDKRB2-58T/C gene polymorphism and risk of hypertension was substantiated in Asians under C allele comparison (OR: 1.24, 95% CI: 1.04-1.49), recessive model (OR: 1.39, 95% CI: 1.04-1.86), dominant model (OR: 0.72, 95% CI: 0.56-0.93), homozygote model (OR: 1.78, 95% CI: 1.09-2.90) and heterozygote model (OR: 1.26, 95% CI: 1.07 1.49). No publication bias was found in the meta-analysis. The meta-analysis suggested -58C allele and -58CC genotype increase the risk of hypertension in Asians and African-Americans. Inversely, -58TT genotype decreases the risk of hypertension in Asians and African-Americans. PMID- 27007664 TI - The proposed physiology-based FDG PET/CT criteria in reducing false-positive results in advanced head and neck cancer after chemoradiotherapy. AB - BACKGROUND: Distinguishing benign complications after concurrent chemoradiotherapy (CCRT) from a local residual tumor in advanced head and neck squamous cell carcinoma (HNSCC) remains a clinical challenge. In this study, we propose criteria when considering physiological uptake patterns on F-18 fluorodeoxyglucose (FDG) PET/CT in patients with advanced HNSCC after CCRT. METHODS: We retrospectively reviewed FDG PET/CT images of 62 patients with advanced HNSCC, which were taken within 16 weeks following CCRT. Visual interpretation criteria were rated by three nuclear medicine physicians, independently, according to the uptake patterns of the primary site. The Cohen k coefficient was calculated to assess inter-reader agreement. The histology of the primary site within a 1 month of the PET/CT study was used as the gold standard for sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: PET/CT was arranged at a median interval of 10.5 weeks (range 4 16 weeks) after CCRT, and the pathologic residual rate was 55.7% at the primary site. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of identifying residual disease were 91.1%, 50.0%, 68.9%, 82.3%, and 72.6%, respectively, by the previously established criteria, and 88.2%, 92.9%, 93.8%, 86.7%, and 90.3%, respectively, by our physiology-based criteria. Our visual rating criteria corrected 12 of 14 (84.6%) false-positive results from the established criteria, while two more false-negative cases identified with our criteria were proven to be small residual tumors. CONCLUSIONS: By incorporating physiological changes following CCRT, our visual rating criteria improved the accuracy of the currently used FDG PET/CT visual rating system, especially the number of false-positive cases with advanced HNSCC after CCRT. PMID- 27007665 TI - Reversible myocardial perfusion defects in patients not suffering from obstructive epicardial coronary artery disease as assessed by coronary angiography. AB - In approximately 10-30% of patients presenting with angina complaints, normal or non-obstructive coronary arteries are found on angiography. In this review paper, available literature on the underlying pathophysiological substrate explaining these discrepancies is reviewed. Both histological studies as well as studies using intravascular ultrasound e.g. the PROSPECT trial, show that epicardial coronary vessel significant lumen stenosis may be delayed until a plaque occupies 40% of the internal elastic lamina area. Limited available data suggest that these angiographically undetectable plaques are associated with an abnormal vasodilation capacity of the coronary circulation and may results in reversible perfusion defects on myocardial perfusion imaging (MPI). Organic non atherosclerotic causes of epicardial coronary artery disease such as anomalous coronary arteries that course between the aorta and pulmonary artery, myocardial bridging and coronary vasospasm may also contribute to MPI results suggesting the presence of ischemia in the presence of normal coronary arteries on coronary angiography. Additional causes of reversible perfusion defects on MPI in the presence of a normal coronary angiogram are intraventricular conduction disturbances. The existence of reversible perfusion defects in the anteroseptal region in most of the patients suffering from left bundle branch block (LBBB) on MPI following physical exercise as stressor is well documented. As the observed reduced septal uptake of both 201Tl and 99mTc-sestamibi/tetrofosmin in LBBB reflects coronary autoregulation in response to lower oxygen demands, not surprisingly, dipyridamole which uniformly exploits flow reserve, has proven more accurate for the diagnosis of coronary artery disease (CAD) in patients suffering from LBBB. Although patients with a permanent ventricular pacemaker have a similar conduction abnormality as patients presenting with a LBBB, most of the defects found on MPI imaging in this patient population (in up to 78% of patients with a normal coronary angiogram that area continuously paced) are localized in the inferoposterior (71%), apical (50%) and inferoseptal (28%) wall; coronary flow velocities in the left anterior descending (LAD) and dominant coronary artery and coronary flow reserve are also significantly lower when compared to a control group. Contrary to what is seen in LBBB patients, dipyridamole stress does not significantly reduce the incidence of abnormalities found but limits the defects to the inferior wall. Furthermore, the frequency of abnormalities found on MPI increases over time with right ventricular outflow tract pacing. Previous histologic studies have shown that microvessel disease is often accompanied by a slow-flow phenomenon reflecting decreased resting flow velocity. Thus, not surprisingly, MPI reversible abnormalities in the presence of a normal coronary angiogram have been reported in a wide variety of diseases characterized by microvessel disease such as diabetes, systemic lupus erythematosus, Behcet's disease and metabolic syndrome. In these patients, low adiponectin and high lipoprotein(a) levels are found which are known to be associated with endothelial dysfunction, atherosclerosis and coronary artery disease. Furthermore, in these patients, limited available data suggest that reversible perfusion defects on MPI confer a significantly poorer prognosis both in terms of hard event rate (MI and cardiac death) and total event rate (MI, cardiac death or late revascularization). It is thus suggested that MPI could discriminate patients with a more severe prognosis. Finally, physical training in patients with primary microvascular angina appears to be associated with reduction of myocardial perfusion abnormalities. PMID- 27007666 TI - Magnetic Resonance Imaging Applications on Infiltrative Cardiomyopathies. AB - Infiltrative cardiomyopathies are a heterogenous group of diseases that typically lead to restrictive cardiac dysfunction. Due to similar phenotypes, accurate diagnosis is challenging without invasive endomyocardial biopsy which has historically been considered mandatory. Cardiac magnetic resonance (CMR) has been well established in the diagnostic workup of patients with suspected cardiomyopathies due to its unique capability for tissue differentiation and its unsurpassed accuracy in defining cardiac morphology and function. The increasing variety of CMR techniques has generated both excitement and uncertainty with regard to their potential clinical use and its role vis-a-vis conventional noninvasive imaging techniques. The purpose of this review is to give an overview of established and emerging CMR techniques and typical image characteristics of the most commonly encountered infiltrative cardiomyopathies. PMID- 27007667 TI - Evaluation of High-Pitch Ungated Pediatric Cardiovascular Computed Tomography for the Assessment of Cardiac Structures in Neonates. AB - PURPOSE: We evaluated a high-pitch, non-electrocardiogram-gated cardiac computed tomographic protocol, designed to image both cardiac and extracardiac structures, including coronary arteries, in a neonatal population (less than 1 year old) that was referred for congenital heart disease assessment and compared it with an optimized standard-pitch protocol in an equivalent cohort. MATERIALS AND METHODS: Twenty-nine high-pitch scans were compared with 31 age-matched, sex-matched, and weight-matched standard-pitch, dosimetrically equivalent scans. The visualization and subjective quality of both cardiac and extracardiac structures were scored by consensus between 2 trained blinded observers. Image noise, signal-to-noise and contrast-to-noise ratios, and radiation doses were also compared. RESULTS: The high-pitch protocol better demonstrated the pulmonary veins (P=0.03) and all coronary segments (all P<0.05), except the distal right coronary artery (P=0.10), with no significant difference in the visualization of the remaining cardiac or extracardiac structures. Both contrast-to-noise and signal-to-noise ratios improved due to greater vessel opacity, with significantly fewer streak (P<0.01) and motion (P<0.01) artifacts. Image noise and computed tomographic dose index were comparable across the 2 techniques; however, the high-pitch acquisition resulted in a small, but statistically significant, increase in dose-length product [13.0 mGy.cm (9.0 to 17.3) vs. 11.0 mGy.cm (9.0 to 13.0), P=0.05] due to greater z-overscanning. CONCLUSIONS: In neonates, a high-pitch protocol improves coronary artery and pulmonary vein delineation compared with the standard-pitch protocol, allowing a more comprehensive assessment of cardiovascular anatomy while obviating the need for either patient sedation or heart rate control. PMID- 27007663 TI - Long noncoding RNAs expressed in human hepatic stellate cells form networks with extracellular matrix proteins. AB - BACKGROUND: Hepatic fibrosis is the underlying cause of cirrhosis and liver failure in nearly every form of chronic liver disease, and hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Long noncoding RNAs (lncRNAs) are increasingly recognized as regulators of development and disease; however, little is known about their expression in human HSCs and their function in hepatic fibrosis. METHODS: We performed RNA sequencing and ab initio assembly of RNA transcripts to define the lncRNAs expressed in human HSC myofibroblasts. We analyzed chromatin immunoprecipitation data and expression data to identify lncRNAs that were regulated by transforming growth factor beta (TGF-beta) signaling, associated with super-enhancers and restricted in expression to HSCs compared with 43 human tissues and cell types. Co-expression network analyses were performed to discover functional modules of lncRNAs, and principle component analysis and K-mean clustering were used to compare lncRNA expression in HSCs with other myofibroblast cell types. RESULTS: We identified over 3600 lncRNAs that are expressed in human HSC myofibroblasts. Many are regulated by TGF-beta, a major fibrotic signal, and form networks with genes encoding key components of the extracellular matrix (ECM), which is the substrate of the fibrotic scar. The lncRNAs directly regulated by TGF-beta signaling are also enriched at super enhancers. More than 400 of the lncRNAs identified in HSCs are uniquely expressed in HSCs compared with 43 other human tissues and cell types and HSC myofibroblasts demonstrate different patterns of lncRNA expression compared with myofibroblasts originating from other tissues. Co-expression analyses identified a subset of lncRNAs that are tightly linked to collagen genes and numerous proteins that regulate the ECM during formation of the fibrotic scar. Finally, we identified lncRNAs that are induced during progression of human liver disease. CONCLUSIONS: lncRNAs are likely key contributors to the formation and progression of fibrosis in human liver disease. PMID- 27007668 TI - Hypomethylating Agents for Relapse after Allogeneic Hematopoietic Cell Transplantation in Myeloid Malignancies: A Case Series and Review of the Literature. AB - BACKGROUND/AIMS: Relapse is a leading cause of mortality after allogeneic hematopoietic cell transplantation (HCT). Hypomethylating agents (HMAs) have immunomodulatory properties, including augmenting tumor antigen presentation that may enhance the graft-versus-leukemia effect. Moreover, inhibitory effects on T cell activation and cytokine production may lead to a lower incidence of graft versus-host disease (GVHD). Our aim was to describe outcomes in patients treated with HMAs for relapse after HCT. METHODS: Subjects were retrospectively identified as patients with relapse or loss of donor chimerism after HCT for myeloid malignancies treated with HMAs at the University of Pittsburgh. RESULTS: Thirteen patients were identified, with a median age of 57 years and a median time to relapse of 98 days. Nine of 12 (75%) evaluable patients had a complete remission (CR). Grade I-IV acute GVHD involving the liver occurred in 6 patients. Cases of acute liver GVHD were diagnosed clinically based on the elevation of liver function tests. The median survival was 14.3 months from the time of relapse. CONCLUSION: HMAs for relapse after HCT can be effective in inducing a CR. This may be due to epigenetic changes and immunomodulatory effects that enhance the graft-versus-leukemia effect. There may be a risk of GVHD, and further exploration into pathophysiology and predisposing factors are warranted. PMID- 27007669 TI - Posaconazole Substitution for Voriconazole-Associated Phototoxic Effects. PMID- 27007670 TI - Resolution of Cardiogenic Shock Using Echocardiography-Guided Pacing Optimization in Intensive Care: A Case Series. AB - OBJECTIVE: Inotropic and vasopressor drugs are routinely used in critically ill patients to maintain adequate blood pressure and cardiac output in patients with cardiogenic shock although potentially at the expense of increasing myocardial oxygen demand. Pacing optimization has been demonstrated as effective in reducing catecholamine requirements in patients with chronic heart failure by improving cardiac efficiency; however, there are no reports relating to the effectiveness of pacemaker optimization on cardiac output in critically ill patients with cardiogenic shock in the intensive care. DATA SOURCES: Retrospective data analysis. STUDY SELECTION: Twenty-bed adult tertiary cardiothoracic ICU, university hospital. DATA EXTRACTION: Eight sequential patients receiving dual chamber pacemaker with DDD modality with cardiogenic shock and hemodynamic instability refractory to catecholamines underwent echocardiography-guided pacemaker optimization of cardiac output. An iterative method with Doppler echocardiography was used to assess changes in cardiac output, left ventricular filling time, ejection time, total isovolumic time, mitral regurgitation, ejection fraction, and blood pressure at different increments of heart rate, and atrioventricular and interventricular delay. All results are shown as median (minimum/maximum level) or mean +/- SD. DATA SYNTHESIS: Using echocardiography guided pacemaker optimization on cardiac output, the cardiac output increased from 3.2 (2.3/3.8) to 5.7 L/min (4.85/7.1) and cardiac index from 1.64 (1.1/1.9) to 2.68 L/min/m (2.1/3.2) and the total isovolumic time reduced from 22.8 to normal values (<14). In association, the glomerular filtration rate increased significantly except in one patient with stage IV chronic kidney disease. All inotropes and vasopressors were discontinued within 12 hours of pacemaker optimization on cardiac output, and all patients were discharged from the ICU within 1 week. CONCLUSIONS: Echocardiography-guided pacemaker optimization of cardiac output is a feasible bedside therapeutic option, which should be considered when standard medical treatments are insufficient for the treatment of cardiogenic shock refractory to inotropic support, thereby minimizing the detrimental effect of catecholamines. PMID- 27007671 TI - Phosphatidylserine Exposure in Human Red Blood Cells Depending on Cell Age. AB - BACKGROUND/AIMS: The exposure of phosphatidylserine (PS) on the outer membrane leaflet of red blood cells (RBCs) serves as a signal for suicidal erythrocyte death or eryptosis, which may be of importance for cell clearance from blood circulation. PS externalisation is realised by the scramblase activated by an increase of intracellular Ca2+ content. It has been described in literature that RBCs show an increased intracellular Ca2+ content as well as PS exposure when becoming aged up to 120 days (which is their life span). However, these investigations were carried out after incubation of the RBCs for 48 h. The aim of this study was to investigate this effect after short-time incubation using a variety of stimulating substances for Ca2+ uptake and PS exposure. METHODS: We separated RBCs by age in five different fractions by centrifugation using Percoll density gradient. The intracellular Ca2+ content and the PS exposure of RBCs with different age has been investigated after treatment with lysophosphatidic acid (LPA) as well as after activation of protein kinase C (PKC) using phorbol-12 myristate-13 acetate (PMA). For positive control RBCs were treated with 4-bromo A23187. Measurement techniques included flow cytometry and live cell imaging (fluorescence microscopy). RESULTS: The percentage of RBCs showing increased Ca2+ content as well as the PS exposure did not change significantly in dependence on cell age after short-time incubation in control experiments (without stimulating substances) or using LPA or PMA. However, we confirm findings reported that Ca2+ content and the PS exposure of RBCs increased after 48 h incubation. CONCLUSION: No significant differences of intracellular Ca2+ content and PS exposure can be seen for RBCs of different age in resting state or after stimulation of Ca2+ uptake at short-time incubation. PMID- 27007672 TI - Does primary productivity modulate the indirect effects of large herbivores? A global meta-analysis. AB - Indirect effects of large mammalian herbivores (LMH), while much less studied than those of apex predators, are increasingly recognized to exert powerful influences on communities and ecosystems. The strength of these effects is spatiotemporally variable, and several sets of authors have suggested that they are governed in part by primary productivity. However, prior theoretical and field studies have generated conflicting results and predictions, underscoring the need for a synthetic global analysis. We conducted a meta-analysis of the direction and magnitude of large mammalian herbivore-initiated indirect interactions using 67 published studies comprising 456 individual responses. We georeferenced 41 of these studies (comprising 253 responses from 33 locations on five continents) to a satellite-derived map of primary productivity. Because predator assemblages might also influence the impact of large herbivores, we conducted a similar analysis using a global map of large carnivore species richness. In general, LMH reduced the abundance of other consumer species and also tended to reduce consumer richness, although the latter effect was only marginally significant. There was a pronounced reduction in the strength of negative (i.e. suppressive, due e.g., to competition) indirect effects of LMH on consumer abundance in more productive ecosystems. In contrast, positive (facilitative) indirect effects were not significantly correlated with productivity, likely because these comprised a more heterogeneous array of mechanisms. We found no effect of carnivore species richness on herbivore initiated indirect effect strength. Our findings help to resolve the fundamental problem of ecological contingency as it pertains to the strength of an understudied class of multitrophic interactions. Moreover, these results will aid in predicting the indirect effects of anthropogenic wildlife declines and irruptions, and how these effects might be mediated by climatically driven shifts in resource availability. To the extent that intact ungulate guilds help to suppress populations of small animals that act as agricultural pests and disease reservoirs, the negative impacts of large mammal declines on human well-being may be relatively stronger in low-productivity areas. PMID- 27007673 TI - Norovirus antagonism of B-cell antigen presentation results in impaired control of acute infection. AB - Human noroviruses are a leading cause of gastroenteritis, and so, vaccine development is desperately needed. Elucidating viral mechanisms of immune antagonism can provide key insight into designing effective immunization platforms. We recently revealed that B cells are targets of norovirus infection. Because noroviruses can regulate antigen presentation by infected macrophages and B cells can function as antigen-presenting cells, we tested whether noroviruses regulate B-cell-mediated antigen presentation and the biological consequence of such regulation. Indeed, murine noroviruses could prevent B-cell expression of antigen presentation molecules and this directly correlated with impaired control of acute infection. In addition to B cells, acute control required MHC class I molecules, CD8+ T cells, and granzymes, supporting a model whereby B cells act as antigen presenting cells to activate cytotoxic CD8+ T cells. This immune pathway was active prior to the induction of antiviral antibody responses. As in macrophages, the minor structural protein VP2 regulated B-cell antigen presentation in a virus-specific manner. Commensal bacteria were not required for the activation of this pathway and ultimately only B cells were required for the clearance of viral infection. These findings provide new insight into the role of B cells in stimulating antiviral CD8+ T-cell responses. PMID- 27007675 TI - A biased view toward celiac disease. AB - Celiac disease is an autoimmune-like disorder that is triggered by dietary gluten and has a strong genetic association with the human leukocyte antigen locus, specifically, HLA-DQ2.5/DQ8. Here, Dahai-Koirala et al. apply ex vivo single-cell sequencing of TCRs from celiac disease patients, and show that biased T-cell receptor usage underpins the response to two gluten epitopes, which has implications for disease pathogenesis, diagnosis, and treatment. PMID- 27007674 TI - Regulatory T cells are essential to promote proper CD4 T-cell priming upon mucosal infection. AB - Regulatory T cells (Tregs) limit autoimmunity and immunopathology using a variety of suppressive mechanisms, but their roles during pathogen-directed immune responses remain unclear. Following herpes simplex virus-2 (HSV-2) infection, mice lacking Tregs fail to control viral replication, pointing to a role for Tregs in facilitating productive immune responses. Using adoptive transfer of T cell receptor transgenic CD4 T cells into Treg-sufficient or Treg-depleted mice prior to HSV-2 infection, we found that Tregs are required for timely accumulation of HSV-2-specific CD4 T cells within the infected tissues. Further, Tregs are critical for appropriate trafficking of dendritic cells (DCs) from the vaginal mucosa to the draining lymph nodes, which results in fully effective CD4 T-cell priming, activation, and ultimately migration to the infected tissues. Using CTLA-4 conditional knockout mice, we demonstrate that Tregs impact DC migration through a CTLA-4-mediated mechanism. Together, our data highlight the critical role of Tregs in proper potentiation of adaptive immune responses to microbial infection. PMID- 27007676 TI - Critical role of caspase-8-mediated IL-1 signaling in promoting Th2 responses during asthma pathogenesis. AB - Allergic asthma is a chronic inflammatory disorder of the airways that affects >300 million people worldwide. The pro-inflammatory cytokines interleukin (IL) 1alpha and IL-1beta have essential roles in the pathogenesis of asthma. However, the mechanisms underlying the production of IL-1 cytokines in allergic asthma remain unclear. In this study, we used a mouse model of ovalbumin-induced asthma to identify a crucial role for caspase-8 in the development of allergic airway inflammation. We further demonstrated that hematopoietic cells have dominant roles in caspase-8-mediated allergic airway inflammation. Caspase-8 was required for the production of IL-1 cytokines to promote Th2 immune response, which promotes the development of pulmonary eosinophilia and inflammation. Thus, our study identifies caspase-8 as a master regulator of IL-1 cytokines that contribute to the pathogenesis of asthma and implicates caspase-8 inhibition as a potential therapeutic strategy for asthmatic patients. PMID- 27007677 TI - Interleukin-22 regulates antimicrobial peptide expression and keratinocyte differentiation to control Staphylococcus aureus colonization of the nasal mucosa. AB - The local immune response occurring during Staphylococcus aureus nasal colonization remains ill-defined. Studies have highlighted the importance of T cell immunity in controlling S. aureus colonization of the nasal mucosa. We extend these observations, identifying a critical role for interleukin (IL)-22 in this process. IL-22 is basally expressed within the nasal mucosa and is induced upon S. aureus colonization. IL-22 is produced by CD4+ and CD8+ T lymphocytes at this site, with innate-like lymphocytes also contributing. IL-22-/- mice demonstrate significantly elevated levels of S. aureus nasal colonization as compared with wild-type (WT) mice. This was associated with reduced expression of antimicrobial peptides (AMPs) in the nose. Furthermore, expression of staphylococcal ligands loricrin and cytokeratin 10 was higher in the noses of IL 22-/- as compared with WT mice. IL-17 has been shown to regulate S. aureus nasal colonization by controlling local neutrophil responses; however, IL-17 expression and neutrophil responses were comparable in the noses of IL-22-/- and WT mice during S. aureus colonization. We conclude that IL-22 has an important role in controlling S. aureus nasal colonization through distinct mechanisms, with IL-22 mediating its effect exclusively by inducing AMP expression and controlling availability of staphylococcal ligands. PMID- 27007678 TI - CD45 regulates GM-CSF, retinoic acid and T-cell homing in intestinal inflammation. AB - CD45 is a leukocyte-specific tyrosine phosphatase important for T-cell development, and as a result, CD45-/- mice have substantially reduced numbers of T cells. Here we show that, upon dextran sodium sulfate (DSS)-induced colitis, CD45-/- mice have equivalent intestinal pathology and T-cell numbers in their colon as C57BL/6 mice and show enhanced weight loss. CD45-/- mice have a greater percentage of alpha4beta7+ T cells prior to and after colitis and an increased percentage of T cells producing inflammatory cytokines in the inflamed colon, suggesting that CD45-/- effector T cells preferentially home to the intestine. In DSS-induced colitis in CD45RAG-/- mice lacking an adaptive immune system, CD45 was required for optimal granulocyte-macrophage colony-stimulating factor (GM CSF) and retinoic acid (RA) production by innate immune cells. Addition of CD45+/+ T cells led to greater weight loss in the RAG-/- mice compared with CD45RAG-/- mice that correlated with reduced alpha4beta7+ T cells and lower recruitment to the colon of CD45RAG-/- mice in DSS-induced colitis. Addition of exogenous GM-CSF to CD45RAG-/- mice rescued RA production, increased colonic T cell numbers, and increased weight loss. This demonstrates opposing effects of CD45 in innate and adaptive immune cells in proinflammatory responses and the expression of the gut-homing molecule, alpha4beta7. PMID- 27007681 TI - Cosmological tests of modified gravity. AB - We review recent progress in the construction of modified gravity models as alternatives to dark energy as well as the development of cosmological tests of gravity. Einstein's theory of general relativity (GR) has been tested accurately within the local universe i.e. the Solar System, but this leaves the possibility open that it is not a good description of gravity at the largest scales in the Universe. This being said, the standard model of cosmology assumes GR on all scales. In 1998, astronomers made the surprising discovery that the expansion of the Universe is accelerating, not slowing down. This late-time acceleration of the Universe has become the most challenging problem in theoretical physics. Within the framework of GR, the acceleration would originate from an unknown dark energy. Alternatively, it could be that there is no dark energy and GR itself is in error on cosmological scales. In this review, we first give an overview of recent developments in modified gravity theories including f(R) gravity, braneworld gravity, Horndeski theory and massive/bigravity theory. We then focus on common properties these models share, such as screening mechanisms they use to evade the stringent Solar System tests. Once armed with a theoretical knowledge of modified gravity models, we move on to discuss how we can test modifications of gravity on cosmological scales. We present tests of gravity using linear cosmological perturbations and review the latest constraints on deviations from the standard [Formula: see text]CDM model. Since screening mechanisms leave distinct signatures in the non-linear structure formation, we also review novel astrophysical tests of gravity using clusters, dwarf galaxies and stars. The last decade has seen a number of new constraints placed on gravity from astrophysical to cosmological scales. Thanks to on-going and future surveys, cosmological tests of gravity will enjoy another, possibly even more, exciting ten years. PMID- 27007679 TI - Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection. AB - Depot-medroxyprogesterone acetate (DMPA) is a hormonal contraceptive especially popular in areas with high prevalence of HIV and other sexually transmitted infections (STI). Although observational studies identify DMPA as an important STI risk factor, mechanisms underlying this connection are undefined. Levonorgestrel (LNG) is another progestin used for hormonal contraception, but its effect on STI susceptibility is much less explored. Using a mouse model of genital herpes simplex virus type 2 (HSV-2) infection, we herein found that DMPA and LNG similarly reduced genital expression of the desmosomal cadherin desmoglein-1alpha (DSG1alpha), enhanced access of inflammatory cells to genital tissue by increasing mucosal epithelial permeability, and increased susceptibility to viral infection. Additional studies with uninfected mice revealed that DMPA-mediated increases in mucosal permeability promoted tissue inflammation by facilitating endogenous vaginal microbiota invasion. Conversely, concomitant treatment of mice with DMPA and intravaginal estrogen restored mucosal barrier function and prevented HSV-2 infection. Evaluating ectocervical biopsy tissue from women before and 1 month after initiating DMPA remarkably revealed that inflammation and barrier protection were altered by treatment identically to changes seen in progestin-treated mice. Together, our work reveals DMPA and LNG diminish the genital mucosal barrier; a first-line defense against all STI, but may offer foundation for new contraceptive strategies less compromising of barrier protection. PMID- 27007680 TI - Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families. AB - OBJECTIVE: While the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D. METHODS: Data from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM 1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes. RESULTS: Decreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment--insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low values for both sICAM-1 and sVCAM-1. The results were similar in women in reproductive age group and the remainder of the cohort. Inclusion of sICAM-1 and sVCAM-1 in predictive models significantly improved reclassification and discrimination. The majority of these results were seen even when the analyses were restricted to NGT individuals. CONCLUSION: Serum concentrations of sICAM-1 and sVCAM-1 independently and additively predict future T2D and represent important candidate biomarkers of T2D. PMID- 27007682 TI - Internal consistency of the self-reporting questionnaire-20 in occupational groups. AB - OBJECTIVE: To assess the internal consistency of the measurements of the Self Reporting Questionnaire (SRQ-20) in different occupational groups. METHODS: A validation study was conducted with data from four surveys with groups of workers, using similar methods. A total of 9,959 workers were studied. In all surveys, the common mental disorders were assessed via SRQ-20. The internal consistency considered the items belonging to dimensions extracted by tetrachoric factor analysis for each study. Item homogeneity assessment compared estimates of Cronbach's alpha (KD-20), the alpha applied to a tetrachoric correlation matrix and stratified Cronbach's alpha. RESULTS: The SRQ-20 dimensions showed adequate values, considering the reference parameters. The internal consistency of the instrument items, assessed by stratified Cronbach's alpha, was high (> 0.80) in the four studies. CONCLUSIONS: The SRQ-20 showed good internal consistency in the professional categories evaluated. However, there is still a need for studies using alternative methods and additional information able to refine the accuracy of latent variable measurement instruments, as in the case of common mental disorders. PMID- 27007683 TI - Maternal mental health and nutritional status of six-month-old infants. AB - OBJECTIVE: To analyze if maternal mental health is associated with infant nutritional status at six month of age. METHODS: A cross-sectional study with 228 six-month-old infants who used primary health care units of the city of Rio de Janeiro, Southeastern Brazil. Mean weight-for-length and mean weight-for-age were expressed in z-scores considering the 2006 World Health Organization reference curves. Maternal mental health was measured by the 12-item General Health Questionnaire. The following cutoff points were used: >= 3 for common mental disorders, >= 5 for more severe mental disorders, and >= 9 for depression. The statistical analysis employed adjusted linear regression models. RESULTS: The prevalence of common mental disorders, more severe mental disorders and depression was 39.9%, 23.7%, and 8.3%, respectively. Children of women with more severe mental disorders had, on average, a weight-for-length 0.37 z-scores lower than children of women without this health harm (p = 0.026). We also observed that the weight-for-length indicator of children of depressed mothers was, on average, 0.67 z-scores lower than that of children of nondepressed women (p = 0.010). Maternal depression was associated with lower mean values of weight-for age z-scores (p = 0.041). CONCLUSIONS: Maternal mental health is positively related to the inadequacy of the nutritional status of infants at six months. PMID- 27007684 TI - Contextual determinants of induced abortion: a panel analysis. AB - OBJECTIVE: Analyze the contextual and individual characteristics that explain the differences in the induced abortion rate, temporally and territorially. METHODS: We conducted an econometric analysis with panel data of the influence of public investment in health and per capita income on induced abortion as well as a measurement of the effect of social and economic factors related to the labor market and reproduction: female employment, immigration, adolescent fertility and marriage rate. The empirical exercise was conducted with a sample of 22 countries in Europe for the 2001-2009 period. RESULTS: The great territorial variability of induced abortion was the result of contextual and individual socioeconomic factors. Higher levels of national income and investments in public health reduce its incidence. The following sociodemographic characteristics were also significant regressors of induced abortion: female employment, civil status, migration, and adolescent fertility. CONCLUSIONS: Induced abortion responds to sociodemographic patterns, in which the characteristics of each country are essential. The individual and contextual socioeconomic inequalities impact significantly on its incidence. Further research on the relationship between economic growth, labor market, institutions and social norms is required to better understand its transnational variability and to reduce its incidence. PMID- 27007685 TI - Sedentary behavior in Brazilian children and adolescents: a systematic review. AB - OBJECTIVE: To describe the methodological characteristics of the studies selected and assess variables associated with sedentary behavior in Brazilian children and adolescents. METHODS: For this systematic review, we searched four electronic databases: PubMed, Web of Knowledge, LILACS, SciELO. Also, electronic searches were applied in Google Scholar. A supplementary search was conducted in the references lists of the included articles and in non-indexed journals. We included observational studies with children and adolescents aged from three to 19 years developed in Brazil, presenting analyses of associations based on regression methods and published until September 30, 2014. RESULTS: Of the 255 potential references retrieved by the searches, 49 met the inclusion criteria and composed the descriptive synthesis. In this set, we identified a great number of cross-sectional studies (n = 43; 88.0%) and high methodological variability on the types of sedentary behavior assessed, measurement tools and cut-off points used. The variables most often associated with sedentary behavior were "high levels of body weight" (in 15 out of 27 studies; 55.0%) and "lower level of physical activity" (in eight out of 16 studies; 50.0%). CONCLUSIONS: The findings of this review raise the following demands to the Brazilian agenda of sedentary behavior research geared to children and adolescents: development of longitudinal studies, validation of measuring tools, establishment of risk cut-offs, measurement of sedentary behavior beyond screen time and use of objective measures in addition to questionnaires. In the articles available, the associations between sedentary behavior with "high levels of body weight" and "low levels of physical activity" were observed in different regions of Brazil. PMID- 27007686 TI - Identification of metabolomics panels for potential lung cancer screening by analysis of exhaled breath condensate. AB - Exhaled breath condensate (EBC) is one of the less employed biofluids when searching for clinical markers, despite its non-invasive sampling and the potential relationship between its composition and respiratory disease phenotypes such as lung cancer. The advanced stage at which lung cancer is usually detected is the main reason for the high mortality rate of this carcinogenic disease. In this preliminary research, EBC was used as clinical sample to develop a screening tool for lung cancer discrimination from two control groups (with and without risk factor). Three panels of metabolites were configured using the PanelomiX tool to minimize false negatives (specificity) and false positives (sensitivity). The combination of five metabolites led to three panels providing a sensitivity above 77.9%, specificity above 67.5% and the area under the curve (AUC) above 77.5% for the three panels. An additional study was developed as a first approach to study the statistical significance of metabolites at different stages of lung cancer. PMID- 27007687 TI - New Insights on Wood Dimensional Stability Influenced by Secondary Metabolites: The Case of a Fast-Growing Tropical Species Bagassa guianensis Aubl. AB - Challenging evaluation of tropical forest biodiversity requires the reporting of taxonomic diversity but also the systematic characterization of wood properties in order to discover new promising species for timber industry. Among wood properties, the dimensional stability is regarded as a major technological characteristic to validate whether a wood species is adapted to commercial uses. Cell structure and organization are known to influence the drying shrinkage making wood density and microfibrils angle markers of choice to predict wood dimensional stability. On the contrary the role of wood extractive content remains unclear. This work focuses on the fast-growing tropical species Bagassa guianensis and we report herein a correlation between heartwood drying shrinkage and extractive content. Chemical extractions and shrinkage experiments were performed on separate wood twin samples to better evaluate correctly how secondary metabolites influence the wood shrinkage behaviour. Extractive content were qualitatively and quantitatively analysed using HPLC and NMR spectroscopy. We found that B guianensis heartwood has a homogeneous low shrinkage along its radius that could not be explained only by its basic density. In fact the low drying shrinkage is correlated to the high extractive content and a corrected model to improve the prediction of wood dimensional stability is presented. Additionally NMR experiments conducted on sapwood and heartwood extracts demonstrate that secondary metabolites biosynthesis occurs in sapwood thus revealing B. guianensis as a Juglans-Type heartwood formation. This work demonstrates that B. guianensis, a fast-growing species associated with high durability and high dimensional stability, is a good candidate for lumber production and commercial purposes. PMID- 27007688 TI - Neural substrates of framing effects in social contexts: A meta-analytical approach. AB - We hypothesize that framing effects (risk-averse in the positive frame and risk seeking in the negative frame) are likely to occur when ambiguous social contexts result in ambiguous or ambivalent risk preferences, leading the decision-maker to search for more subtle cues, such as verbal framing. In a functional magnetic resonance imaging (fMRI) study, we examined framing effects in both unambiguous homogeneous group and more ambiguous heterogeneous group contexts. We began by conducting a meta-analysis and identified three regions of interest: the right inferior frontal gyrus, the left anterior cingulate (ACC)/ventromedial prefrontal cortex (vmPFC), and the left amygdala. Our own fMRI data were collected while the participants made choices between a sure option and a gamble framed in terms of the number of lives to either save or die. The framing effect was evident in a heterogeneous context with a mixture of kin and strangers, but disappeared in a homogeneous group of either all kin-members or all strangers. The fMRI results revealed a greater activation in the right middle/inferior frontal gyrus under the negative than the positive framing, and less ACC/vmPFC deactivation under positive framing in the heterogamous/ambiguous context. The activation of the amygdala was correlated with greater risk-seeking preference in homogeneous kinship contexts. PMID- 27007689 TI - Tabulate Corals after the Frasnian/Famennian Crisis: A Unique Fauna from the Holy Cross Mountains, Poland. AB - Famennian tabulate corals were very rare worldwide, and their biodiversity was relatively low. Here we report a unique tabulate fauna from the mid- and late Famennian of the western part of the Holy Cross Mountains (Kowala and Ostrowka), Poland. We describe eight species (four of them new, namely ?Michelinia vinni sp. nov., Thamnoptychia mistiaeni sp. nov., Syringopora kowalensis sp. nov. and Syringopora hilarowiczi sp. nov.); the whole fauna consists of ten species (two others described in previous papers). These corals form two assemblages-the lower, mid-Famennian with Thamnoptychia and the upper, late Famennian with representatives of genera ?Michelinia, Favosites, Syringopora and ?Yavorskia. The Famennian tabulates from Kowala represent the richest Famennian assemblage appearing after the F/F crisis (these faunas appear some 10 Ma after the extinction event). Corals described here most probably inhabited deeper water settings, near the limit between euphotic and disphotic zones or slightly above. At generic level, these faunas show similarities to other Devonian and Carboniferous faunas, which might suggest their ancestry to at least several Carboniferous lineages. Tabulate faunas described here represent new recruits (the basin of the Holy Cross mountains was not a refuge during the F/F crisis) and have no direct evolutionary linkage to Frasnian faunas from Kowala. The colonization of the seafloor took place in two separate steps: first was monospecific assemblage of Thamnoptychia, and later came the diversified Favosites-Syringopora-Michelinia fauna. PMID- 27007690 TI - Impact of an Alcohol Poisoning Storyline in a Fictional Television Program: An Experimental Study With a Live-to-Air Stimulus. AB - Storylines in fictional television programs may be an effective medium for health promoting messages. This randomized pretest-posttest (N = 111) with follow-up (n = 71) study examined the persuasive impact of an alcohol poisoning story in the program ER on viewers' drinking-related beliefs, attitudes, intentions, and behavior. The perception of persuasive intent is theorized to be a key factor influencing a narrative's impact; therefore, this study also examined the influence of perceived persuasive intent on viewing outcomes. Viewing group participants were asked to view a specific upcoming episode of ER when it was first scheduled to air on national television in New Zealand. The results suggest that the alcohol poisoning story had a beneficial impact on viewers' drinking related beliefs, attitudes, and intentions. Perceived persuasive intent was not a significant predictor of viewing outcomes. This study is the first randomized experiment that has used a live-to-air stimulus to examine the impact of a health promoting storyline in a fictional television program that has been created and broadcast in a developed nation. The significant effects found at post-viewing and follow-up provide further empirical support to the existing experimental literature, with enhanced ecological validity, for the potential positive impact of health-promoting storylines in fictional television programs. PMID- 27007691 TI - Long-Term Results of GH Treatment in Silver-Russell Syndrome (SRS): Do They Benefit the Same as Non-SRS Short-SGA? AB - CONTEXT: Silver-Russell syndrome (SRS) is a genetically heterogeneous syndrome characterized by low birth weight, severe short stature, and variable dysmorphic features. GH treatment is a registered growth-promoting therapy for short children born small for gestational age, including SRS, but there are limited data on the GH response in SRS children and on differences in response among the (epi)genetic SRS subtypes (11p15 aberrations, maternal uniparental disomy of chromosome 7 [mUPD7], and idiopathic SRS). OBJECTIVES: To compare growth and adult height between GH-treated small for gestational age children with and without SRS (non-SRS), and to analyze the difference in GH response among SRS genotypes. DESIGN AND SETTING: A longitudinal study. PARTICIPANTS: Sixty-two SRS and 227 non-SRS subjects. INTERVENTION: All subjects received GH treatment (1 mg/m(2)/d). MAIN OUTCOME MEASURES: Adult height and total height gain. RESULTS: The SRS group consisted of 31 children with 11p15 aberrations, 11 children with mUPD7, and 20 children with idiopathic SRS. At the start of GH treatment, mean (SD) height standard deviation score [SDS] was significantly lower in SRS (-3.67 [1.0]) than in non-SRS (-2.92 [0.6]; P < .001). Adult height SDS was lower in SRS (-2.17 [0.8]) than in non-SRS (-1.65 [0.8]; P = .002), but the total height gain SDS was similar. There was a trend toward a greater height gain in mUPD7 than in 11p15 (P = .12). CONCLUSION: Children with SRS have a similar height gain during GH treatment as non-SRS subjects. All (epi)genetic SRS subtypes benefit from GH treatment, with a trend toward mUPD7 and idiopathic SRS having the greatest height gain. PMID- 27007692 TI - Affordable Care Act Implementation: Challenges and Opportunities to Impact Patients With Diabetes. PMID- 27007695 TI - How Lead Halide Complex Chemistry Dictates the Composition of Mixed Halide Perovskites. AB - Varying the halide ratio (e.g., Br(-):I(-)) is a convenient approach to tune the bandgap of organic lead halide perovskites. The complexation between Pb(2+) and halide ions is the primary step in dictating the overall composition, and optical properties of the annealed perovskite structure. The complexation between Pb(2+) and Br(-) is nearly 7 times greater than the complexation between Pb(2+) and I( ), thus making Br(-) a dominant binding species in mixed halide systems. Emission and transient absorption measurements show a strong dependence of excited state behavior on the composition of halide ions employed in the precursor solution. When excess halide (X = Br(-) and I(-)) are present in the precursor solution (0.3 M PbX2 and 0.9 M CH3NH3X), the exclusive binding of Pb(2+) with Br(-) results in the formation of CH3NH3PbBr3 perovskites as opposed to mixed halide perovskite. PMID- 27007694 TI - The Early Endocrine Stress Response in Experimental Subarachnoid Hemorrhage. AB - INTRODUCTION: In patients with severe illness, such as aneurysmal subarachnoid hemorrhage (SAH), a physiologic stress response is triggered. This includes activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The aim of this study was to investigate the very early responses of these systems. METHODS: A porcine animal model of aneurysmal SAH was used. In this model, blood is injected slowly to the basal cisterns above the anterior skull base until the cerebral perfusion pressure is 0 mm Hg. Sampling was done from blood and urine at -10, +15, +75 and +135 minutes from time of induction of SAH. Analyses of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, catecholamines and chromogranin-A were performed. RESULTS: Plasma ACTH, serum cortisol and plasma aldosterone increased in the samples following induction of SAH, and started to decline after 75 minutes. Urine cortisol also increased after SAH. Urine catecholamines and their metabolites were found to increase after SAH. Many samples were however below detection level, not allowing for statistical analysis. Plasma chromogranin-A peaked at 15 minutes after SAH, and thereafter decreased. CONCLUSIONS: The endocrine stress response after aneurysmal SAH was found to start within 15 minutes in the HPA axis with early peak values of ACTH, cortisol and aldosterone. The fact that the concentrations of the HPA axis hormones decreased 135 minutes after SAH may suggest that a similar pattern exists in SAH patients, thus making it difficult to catch these early peak values. There were also indications of early activation of the sympathetic nervous system, but the small number of valid samples made interpretation difficult. PMID- 27007693 TI - Free 25-Hydroxyvitamin D: Impact of Vitamin D Binding Protein Assays on Racial Genotypic Associations. AB - CONTEXT: Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD. OBJECTIVES: Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD. DESIGN: This study used a cross-sectional design. SETTING: The general community in the United States, United Kingdom, and The Gambia were included in this study. PARTICIPANTS: Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included. EXPOSURES: Total 25OHD concentration, race, and DBP (GC) genotype exposures were included. OUTCOME MEASURES: Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures. RESULTS: Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80-0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites. CONCLUSIONS: Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population. PMID- 27007696 TI - Quantitative and Qualitative Responses to Topical Cold in Healthy Caucasians Show Variance between Individuals but High Test-Retest Reliability. AB - Increased sensitivity to cold may be a predictor of persistent pain, but cold pain threshold is often viewed as unreliable. This study aimed to determine the within-subject reliability and between-subject variance of cold response, measured comprehensively as cold pain threshold plus pain intensity and sensation quality at threshold. A test-retest design was used over three sessions, one day apart. Response to cold was assessed at four sites (thenar eminence, volar forearm, tibialis anterior, plantar foot). Cold pain threshold was measured using a Medoc thermode and standard method of limits. Intensity of pain at threshold was rated using a 10cm visual analogue scale. Quality of sensation at threshold was quantified with indices calculated from subjects' selection of descriptors from a standard McGill Pain Questionnaire. Within-subject reliability for each measure was calculated with intra-class correlation coefficients and between subject variance was evaluated as group coefficient of variation percentage (CV%). Gender and site comparisons were also made. Forty-five healthy adults participated: 20 male, 25 female; mean age 29 (range 18-56) years. All measures at all four test sites showed high within-subject reliability: cold pain thresholds r = 0.92-0.95; pain rating r = 0.93-0.97; McGill pain quality indices r = 0.87-0.85. In contrast, all measures showed wide between-subject variance (CV% between 51.4% and 92.5%). Upper limb sites were consistently more sensitive than lower limb sites, but equally reliable. Females showed elevated cold pain thresholds, although similar pain intensity and quality to males. Females were also more reliable and showed lower variance for all measures. Thus, although there was clear population variation, response to cold for healthy individuals was found to be highly reliable, whether measured as pain threshold, pain intensity or sensation quality. A comprehensive approach to cold response testing therefore may add validity and improve acceptance of this potentially important pain measure. PMID- 27007697 TI - Have Tobacco 21 Laws Come of Age? PMID- 27007698 TI - Predicting Risk for Suicide: A Preliminary Examination of Non-Suicidal Self Injury and the Acquired Capability Construct in a College Sample. AB - The interpersonal psychological theory of suicide provides a useful framework for considering the relationship between non-suicidal self-injury and suicide. Researchers propose that NSSI increases acquired capability for suicide. We predicted that both NSSI frequency and the IPTS acquired capability construct (decreased fear of death and increased pain tolerance) would separately interact with suicidal ideation to predict suicide attempts. Undergraduate students (N = 113) completed self-report questionnaires, and a subsample (n = 66) also completed a pain sensitivity task. NSSI frequency significantly moderated the association between suicidal ideation and suicide attempts. However, in a separate model, acquired capability did not moderate this relationship. Our understanding of the relationship between suicidal ideation and suicidal behavior can be enhanced by factors associated with NSSI that are distinct from the acquired capability construct. PMID- 27007700 TI - Relative Abundance in Bacterial and Fungal Gut Microbes in Obese Children: A Case Control Study. AB - BACKGROUND: Differences in relative proportions of gut microbial communities in adults have been correlated with intestinal diseases and obesity. In this study we evaluated the gut microbiota biodiversity, both bacterial and fungal, in obese and normal-weight school-aged children. METHODS: We studied 28 obese (mean age 10.03 +/- 0.68) and 33 age- and sex-matched normal-weight children. BMI z-scores were calculated, and the obesity condition was defined according to the WHO criteria. Fecal samples were analyzed by 16S rRNA amplification followed by denaturing gradient gel electrophoresis (DGGE) analysis and sequencing. Real-time polymerase chain reaction (PCR) was performed to quantify the most representative microbial species and genera. RESULTS: DGGE profiles showed high bacterial biodiversity without significant correlations with BMI z-score groups. Compared to bacterial profiles, we observed lower richness in yeast species. Sequence of the most representative bands gave back Eubacterium rectale, Saccharomyces cerevisiae, Candida albicans, and C. glabrata as present in all samples. Debaryomyces hansenii was present only in two obese children. Obese children revealed a significantly lower abundance in Akkermansia muciniphyla, Faecalibacterium prausnitzii, Bacteroides/Prevotella group, Candida spp., and Saccharomyces spp. (P = 0.031, P = 0.044, P = 0.003, P = 0.047, and P = 0.034, respectively). CONCLUSION: Taking into account the complexity of obesity, our data suggest that differences in relative abundance of some core microbial species, preexisting or diet driven, could actively be part of its etiology. This study improved our knowledge about the fungal population in the pediatric school age population and highlighted the need to consider the influence of cross kingdom relationships. PMID- 27007699 TI - Regulation of Exacerbated Immune Responses in Human Peripheral Blood Cells by Hydrolysed Egg White Proteins. AB - The anti-allergic potential of egg white protein hydrolysates (from ovalbumin, lysozyme and ovomucoid) was evaluated as their ability to hinder cytokine and IgE production by Th2-skewed human peripheral blood mononuclear cells (PBMCs), as well as the release of pro-inflammatory factors and generation of reactive oxygen species from Th1-stimulated peripheral blood leukocytes (PBLs). The binding to IgE of egg allergic patients was determined and the peptides present in the hydrolysates were identified. The hydrolysates with alcalase down-regulated the production of Th2-biased cytokines and the secretion of IgE to the culture media of Th2-skewed PBMCs, and they significantly neutralized oxidative stress in PBLs. The hydrolysates of ovalbumin and ovomucoid with pepsin helped to re-establish the Th1/Th2 balance in Th2-biased PBMCs, while they also inhibited the release of pro-inflammatory mediators and reduced oxidative stress in PBLs treated with inflammatory stimuli. The hydrolysates with alcalase, in addition to equilibrating Th2 differentiation, exhibited a low IgE-binding. Therefore, they would elicit mild allergic reactions while retaining T cell-stimulating abilities, which might correlate with an anti-allergic benefit. PMID- 27007701 TI - Peptidomimetic Star Polymers for Targeting Biological Ion Channels. AB - Four end-functionalized star polymers that could attenuate the flow of ionic currents across biological ion channels were first de novo designed computationally, then synthesized and tested experimentally on mammalian K+ channels. The 4-arm ethylene glycol conjugate star polymers with lysine or a tripeptide attached to the end of each arm were specifically designed to mimic the action of scorpion toxins on K+ channels. Molecular dynamics simulations showed that the lysine side chain of the polymers physically occludes the pore of Kv1.3, a target for immuno-suppression therapy. Two of the compounds tested were potent inhibitors of Kv1.3. The dissociation constants of these two compounds were computed to be 0.1 MUM and 0.7 MUM, respectively, within 3-fold to the values derived from subsequent experiments. These results demonstrate the power of computational methods in molecular design and the potential of star polymers as a new infinitely modifiable platform for ion channel drug discovery. PMID- 27007702 TI - Inducing Transient Charge State of a Single Water Cluster on Cu(111) Surface. AB - The hydrated electron on solid surface is a crucial species to interfacial chemistry. We present a joint low-temperature scanning tunneling microscopy and density functional theory investigation to explore the existence of a transient hydrated electron state induced by injecting tunneling electrons into a single water nonamer cluster on Cu(111) surface. The directional diffusion of water cluster under the Coulomb repulsive potential has been observed as evidence for the emergence of the transient hydrated electron. A critical structure transformation in water cluster for the emergence of hydrated electron has been identified. A charging mechanism has been proposed based on density functional theory calculation and scanning tunneling microscope results. PMID- 27007704 TI - Detection of pneumolabyrinth after temporal bone trauma using computed tomography. AB - CONCLUSION: Pneumolabyrinth is a very rare condition, even in otic capsule disrupting (OCD) fracture. Hearing was not always impaired, even in cases with OCD fracture. The co-existence of pneumocochlea, regarded as a risk factor for total hearing loss, was extremely rare in cases of pneumolabyrinth. OBJECTIVES: The purposes of this study were to analyze the radiological and clinical features in patients with pneumolabyrinth and to overcome the diagnostic pitfalls encountered during pneumocochlea detection. MATERIALS AND METHODS: The temporal bone computed tomographies (TBCT) of 402 patients diagnosed with temporal bone fracture along with their clinical records were retrospectively reviewed. RESULTS: Only six patients (7% of those with OCD fractures or 1.5% of those with temporal bone fracture) were found to have pneumolabyrinth. Locations of the pneumolabyrinth were in the vestibule in all six cases and three of them showed air densities both in the cochlea and semicircular canal. The size of the air density in the vestibule was 5.38 +/- 4.56 mm(2) at the axial view and 6.57 +/- 5.67 mm(2) at the coronal view. The mean minimal Hounsfield unit (HU) of air density area in the vestibule was -968.1 +/- 22.94 at the axial view and -941 +/- 16.88 at the coronal view. Patients with pneumocochlea eventually developed total hearing loss. PMID- 27007703 TI - Disruption of the ovarian follicle reservoir of prepubertal rats following prenatal exposure to a continuous 900-MHz electromagnetic field. AB - The effects on human health of electromagnetic field (EMF) have begun to be seriously questioned with the entry into daily life of devices establishing EMF, such as cell phones, wireless fidelity, and masts. Recent studies have reported that exposure to EMF, particularly during pregnancy, affects the developing embryo/fetus. The aim of this study was therefore to examine the effects of exposure to continuous 900-Megahertz (MHz) EMF applied in the prenatal period on ovarian follicle development and oocyte differentiation. Six pregnant Sprague Dawley rats were divided equally into a non-exposed control group (CNGr) and a group (EMFGr) exposed to continuous 900-MHz EMF for 1 h daily, at the same time every day, on days 13-21 of pregnancy. New groups were established from pups obtained from both groups after birth. One group consisting of female pups from CNGr rats was adopted as newborn CNGr (New-CNGr, n = 6), and another group consisting of female pups from EMFGr rats was adopted as newborn EMFGr (New EMFGr, n = 6). No procedure was performed on New-CNGr or New-EMFGr rats. All rat pups were sacrificed on the postnatal 34th day, and their ovarian tissues were removed. Follicle count, histological injury scoring and morphological assessment with apoptotic index criteria were performed with sections obtained following routine histological tissue preparation. Follicle count results revealed a statistically significant decrease in primordial and tertiary follicle numbers in New-EMFGr compared to New-CNGr (p < 0.05), while atretic follicle numbers and apoptotic index levels increased significantly (p < 0.05). Histopathological examination revealed severe follicle degeneration, vasocongestion, a low level of increased stromal fibrotic tissue and cytoplasmic vacuolization in granulosa cell in New-EMFGr. Prenatal exposure to continuous 900-MHz EMF for 1 h each day from days 13-21 led to a decrease in ovarian follicle reservoirs in female rat pups at the beginning of the prepubertal period. PMID- 27007709 TI - Comparison of two MR grading systems for correlation between grade of cervical neural foraminal stenosis and clinical manifestations. AB - OBJECTIVE: To compare the reliability of two recently reported MR grading systems of cervical neural foraminal stenosis (CNFS) and their correlation with clinical manifestations. METHODS: We evaluated 188 patients (male : female = 80 : 108; mean age of 41 years) who visited our institution and underwent oblique sagittal MRI of the cervical spine. Two radiologists evaluated the MRI findings for the presence and grade of CNFS at the narrowest point, with the grading systems (Park, Kim and mKim systems) suggested by Park et al and Kim et al. More than one positive neurologic sign and more than one neurologic clinical symptom was considered a positive neurologic manifestation of each foraminal stenosis. Interobserver agreement between the two readers was analyzed using kappa statistics. Non-parametric correlation analysis (Spearman's correlation) was used to evaluate the correlation coefficients (R) to assess the relationship between CNFS grade and clinical manifestations. RESULTS: Both the Park and mKim systems demonstrated a relatively high correlation (R = 0.714-0.764) between the CNFS grade and clinical manifestation, while the Kim system yielded a moderate correlation (by Reader 2). The Park and mKim systems demonstrated higher correlation values at the level of C6-7 than C4-5, while the Kim system showed no difference in correlation at the cervical spine level. CONCLUSION: Both the Park and mKim systems provide a reliable, reproducible CNFS diagnosis, while the Kim system has a slightly inferior reliability. The Park and mKim systems had a similar, relatively high clinical correlation. ADVANCES IN KNOWLEDGE: Grades 2 and 3 of the Park system and Grade 2 in the Kim and mKim systems exhibited a similar clinical significance. Patients with a grade of 0 (using each system) consistently exhibit negative neurologic manifestation. PMID- 27007710 TI - Targeting colorectal cancer-associated bacteria: A new area of research for personalized treatments. AB - Most cases of colorectal cancer (CRC) are sporadic, and numerous studies have suggested that gut microbiota may play a crucial role in CRC development. Escherichia coli is a member of the gut microbiota frequently associated with colorectal tumors. CRC-associated E. coli strains frequently harbor the pks genomic island. This genomic island is responsible for the synthesis of colibactin genotoxin, which increases tumor numbers in CRC mouse models. We recently showed that targeting ClbP, a key enzyme involved in colibactin synthesis, blocks the deleterious effect of this toxin in vitro and leads to a significant decrease in tumor numbers in vivo. Altogether, our results suggest that the personalized treatment of CRC should also take into consideration the bacteria associated with the tumor in order to limit their deleterious effects. PMID- 27007711 TI - Osmolyte Effects on Monoclonal Antibody Stability and Concentration-Dependent Protein Interactions with Water and Common Osmolytes. AB - Preferential interactions of proteins with water and osmolytes play a major role in controlling the thermodynamics of protein solutions. While changes in protein stability and shifts in phase behavior are often reported with the addition of osmolytes, the underlying protein interactions with water and/or osmolytes are typically inferred rather than measured directly. In this work, Kirkwood-Buff integrals for protein-water interactions (G12) and protein-osmolyte interactions (G23) were determined as a function of osmolyte concentration from density measurements of antistreptavidin immunoglobulin gamma-1 (AS-IgG1) in ternary aqueous solutions for a set of common neutral osmolytes: sucrose, trehalose, sorbitol, and poly(ethylene glycol) (PEG). For sucrose and PEG solutions, both protein-water and protein-osmolyte interactions depend strongly on osmolyte concentrations (c3). Strikingly, both osmolytes change from being preferentially excluded to preferentially accumulated with increasing c3. In contrast, sorbitol and trehalose solutions do not show large enough preferential interactions to be detected by densimetry. G12 and G23 values are used to estimate the transfer free energy for native AS-IgG1 (DeltaMU2N) and compared with existing models. AS-IgG1 unfolding via calorimetry shows a linear increase in midpoint temperatures as a function of trehalose, sucrose, and sorbitol concentrations, but the opposite behavior for PEG. Together, the results highlight limitations of existing models and common assumptions regarding the mechanisms of protein stabilization by osmolytes. Finally, PEG preferential interactions destabilize the Fab regions of AS-IgG1 more so than the CH2 or CH3 domains, illustrating preferential interactions can be specific to different protein domains. PMID- 27007713 TI - Pyoverdine and histicorrugatin-mediated iron acquisition in Pseudomonas thivervalensis. AB - The genome of Pseudomonas thivervalensis LMG 21626(T) has been sequenced and a genomic, genetic and structural analysis of the siderophore mediated iron acquisition was undertaken. Pseudomonas thivervalensis produces two structurally new siderophores, pyoverdine PYOthi which is typical for P. thivervalensis strains and a closely related strain, and the lipopeptidic siderophore histicorrugatin which is also detected in P. lini. Histicorrugatin consists out of an eight amino acid long peptide which is linked to octanoic acid. It is structurally related to the siderophores corrugatin and ornicorrugatin. Analysis of the proteome for TonB-dependent receptors identified 25 candidates. Comparison of the TonB-dependent receptors of P. thivervalensis with the 17 receptors of its phylogenetic neighbor, P. brassicacearum subsp. brassicacearum NFM 421, showed that NFM 421 shares the same set of receptors with LMG 21626(T), including the histicorrugatin receptor. An exception was found for their cognate pyoverdine receptor which can be explained by the observation that both strains produce structurally different pyoverdines. Mass analysis showed that NFM 421 did not produce histicorrugatin, but the analogue ornicorrugatin. Growth stimulation assays with a variety of structurally distinct pyoverdines produced by other Pseudomonas species demonstrated that LMG 21626(T) and NFM 421 are able to utilize almost the same set of pyoverdines. Strain NFM 421 is able utilize two additional pyoverdines, pyoverdine of P. fluorescens Pf0-1 and P. citronellolis LMG 18378(T), these pyoverdines are probably taken up by the FpvA receptor of NFM 421. PMID- 27007712 TI - Lipocalin 2 alleviates iron toxicity by facilitating hypoferremia of inflammation and limiting catalytic iron generation. AB - Iron is an essential transition metal ion for virtually all aerobic organisms, yet its dysregulation (iron overload or anemia) is a harbinger of many pathologic conditions. Hence, iron homeostasis is tightly regulated to prevent the generation of catalytic iron (CI) which can damage cellular biomolecules. In this study, we investigated the role of iron-binding/trafficking innate immune protein, lipocalin 2 (Lcn2, aka siderocalin) on iron and CI homeostasis using Lcn2 knockout (KO) mice and their WT littermates. Administration of iron either systemically or via dietary intake strikingly upregulated Lcn2 in the serum, urine, feces, and liver of WT mice. However, similarly-treated Lcn2KO mice displayed elevated CI, augmented lipid peroxidation and other indices of organ damage markers, implicating that Lcn2 responses may be protective against iron induced toxicity. Herein, we also show a negative association between serum Lcn2 and CI in the murine model of dextran sodium sulfate (DSS)-induced colitis. The inability of DSS-treated Lcn2KO mice to elicit hypoferremic response to acute colitis, implicates the involvement of Lcn2 in iron homeostasis during inflammation. Using bone marrow chimeras, we further show that Lcn2 derived from both immune and non-immune cells participates in CI regulation. Remarkably, exogenous rec-Lcn2 supplementation suppressed CI levels in Lcn2KO serum and urine. Collectively, our results suggest that Lcn2 may facilitate hypoferremia, suppress CI generation and prevent iron-mediated adverse effects. PMID- 27007714 TI - London Education and Inclusion Project (LEIP): Results from a Cluster-Randomized Controlled Trial of an Intervention to Reduce School Exclusion and Antisocial Behavior. AB - School exclusion as a disciplinary measure remains a controversial issue. In spite of numerous attempts to reduce this practice, no solutions with documented effectiveness exist. This article reports results of a cluster-randomized controlled field trial carried out in 36 schools across London. The trial is an independent evaluation of a 12-week-long intervention, Engage in Education-London (EiE-L), delivered by Catch22. The intervention was aimed at students in secondary school who are most at risk of school exclusion. It targeted their social communication and broader social skills with the aim of reducing school exclusions and problem behaviors. The study employed a multi-informant design that included students and teacher reports as well as official records for exclusions and arrests. Data were analyzed through intent-to-treat analyses based on self-reports from 644 students and 685 teacher reports for students who were nominated for the study and for whom data was available at baseline or post intervention. At baseline data collection the students ranged in age from 12.85 to 15.03, with M = 14.03; 71 % were male and included a number of ethnic minorities, the largest of which was black African/black Caribbean comprising 40 % of the sample. The results suggested a small but statistically significant negative effect on the primary outcome of exclusion and null effects for the secondary outcomes that measured behavioral and socio-emotional outcomes. The study's findings are discussed in terms of the possible reasons for the null effects and negative (iatrogenic) effect. PMID- 27007715 TI - Comparing Two Low Middle School Social and Emotional Learning Program Formats: A Multilevel Effectiveness Study. AB - Understanding which factors are relevant for the effectiveness of social and emotional learning programs is of key importance in designing interventions. This study investigated the effectiveness of a universal, school-based, social and emotional learning program for low middle school students (5th and 6th grades) and compared two program delivery formats for the intervention: curriculum (a semi-structured format) and pre-package (fixed structure).The program also analyzed differential gender effects. There were 982 participants (M age = 11.22; SD = 1.02, 46.8 % girls): 318 in the control condition, 355 students in the intervention delivered with a curriculum format and 309 in the intervention delivered in a pre-package format, assessed at pretest, posttest and follow-up eight months later. Multilevel analyses identified positive intervention results in social awareness, self-control, self-esteem, social isolation and social anxiety. The pre-packaged format led to better results in self-esteem and social isolation. Boys gained more in social awareness in both program delivery formats. These findings support the program's effectiveness and the importance of designing the intervention to match program delivery formats with developmental needs. PMID- 27007716 TI - Cyanovirin-N produced in rice endosperm offers effective pre-exposure prophylaxis against HIV-1BaL infection in vitro. AB - KEY MESSAGE: Cyanovirin-N produced in rice endosperm provides efficient pre exposure prophylaxis against HIV-1 BaL infection in vitro. Cyanovirin-N (CV-N) is a lectin with potent antiviral activity that has been proposed as a component of microbicides for the prevention of infection with Human immunodeficiency virus (HIV). The production of protein-based microbicide components requires a platform that is sufficiently economical and scalable to meet the demands of the large at risk population, particularly in resource poor developing countries. We, therefore, expressed CV-N in rice endosperm, because the dried seed is ideal for storage and transport and crude extracts could be prepared locally and used as a microbicide component without further purification. We found that crude extracts from rice seeds expressing up to 10 ug CV-N per gram dry seed weight showed dose dependent gp120 binding activity, confirming that the protein was soluble, correctly folded and active. The recombinant lectin ((OS)CV-N) reduced the infectivity of HIV-1BaL (an R5 virus strain representing the majority of transmitted infections) by ~90 % but showed only weak neutralization activity against HIV-1RF (representative of X4 virus, rarely associated with transmission), suggesting it would be highly effective for pre-exposure prophylaxis against the vast majority of transmitted strains. Crude extracts expressing (OS)CV-N showed no toxicity towards human cells at working dilutions indicating that microbicide components produced in rice endosperm are safe for direct application as topical microbicides in humans. PMID- 27007717 TI - Effective screen of CRISPR/Cas9-induced mutants in rice by single-strand conformation polymorphism. AB - KEY MESSAGE: A method based on DNA single-strand conformation polymorphism is demonstrated for effective genotyping of CRISPR/Cas9-induced mutants in rice. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) has been widely adopted for genome editing in many organisms. A large proportion of mutations generated by CRISPR/Cas9 are very small insertions and deletions (indels), presumably because Cas9 generates blunt-ended double-strand breaks which are subsequently repaired without extensive end processing. CRISPR/Cas9 is highly effective for targeted mutagenesis in the important crop, rice. For example, homozygous mutant seedlings are commonly recovered from CRISPR/Cas9-treated calli. However, many current mutation detection methods are not very suitable for screening homozygous mutants that typically carry small indels. In this study, we tested a mutation detection method based on single-strand conformational polymorphism (SSCP). We found it can effectively detect small indels in pilot experiments. By applying the SSCP method for CRISRP-Cas9-mediated targeted mutagenesis in rice, we successfully identified multiple mutants of OsROC5 and OsDEP1. In conclusion, the SSCP analysis will be a useful genotyping method for rapid identification of CRISPR/Cas9-induced mutants, including the most desirable homozygous mutants. The method also has high potential for similar applications in other plant species. PMID- 27007718 TI - Genome-Wide Studies of Type 2 Diabetes and Lipid Traits in Hispanics. AB - Although disproportionately affected by increasing rates of type 2 diabetes and dyslipidemias, Hispanic populations are underrepresented in efforts to understand genetic susceptibility to these disorders. Where research has been undertaken, these populations have provided substantial insight into identification of novel risk-associated genes and have aided in the ability to fine map previously described risk loci. Genome-wide analyses in Hispanic and trans-ethnic populations have resulted in identification of more than 40 replicated or novel genes with significant effects for type 2 diabetes or lipid traits. Initial investigations into rare variant effects have identified new risk-associated variants private to Hispanic populations, and preliminary results suggest metagenomic approaches in Hispanic populations, such as characterizing the gut microbiome, will enable the development of new predictive tools and therapeutic targets for type 2 diabetes. Future genome-wide studies in expanded cohorts of Hispanics are likely to result in new insights into the genetic etiology of metabolic health. PMID- 27007720 TI - Projecting the effects of long-term care policy on the labor market participation of primary informal family caregivers of elderly with disability: insights from a dynamic simulation model. AB - BACKGROUND: Using Singapore as a case study, this paper aims to understand the effects of the current long-term care policy and various alternative policy options on the labor market participation of primary informal family caregivers of elderly with disability. METHODS: A model of the long-term care system in Singapore was developed using System Dynamics methodology. RESULTS: Under the current long-term care policy, by 2030, 6.9 percent of primary informal family caregivers (0.34 percent of the domestic labor supply) are expected to withdraw from the labor market. Alternative policy options reduce primary informal family caregiver labor market withdrawal; however, the number of workers required to scale up long-term care services is greater than the number of caregivers who can be expected to return to the labor market. CONCLUSIONS: Policymakers may face a dilemma between admitting more foreign workers to provide long-term care services and depending on primary informal family caregivers. PMID- 27007721 TI - Effect of hyaluronic acid in bone formation and its applications in dentistry. AB - Hyaluronic acid (HA), the simplest glycosaminoglycan, participates in several important biological procedures, including mediation of cellular signaling, regulation of cell adhesion and proliferation, and manipulation of cell differentiation. The effect of HA on cell proliferation and differentiation depends on its molecular weight (MW) and concentration. Moreover, the properties of high viscosity, elasticity, highly negative charge, biocompatibility, biodegradability, and nonimmunogenicity make HA attractive in tissue engineering and disease treatment. This review comprises an overview of the effect of HA on cell proliferation and differentiation in vitro, the role of HA in bone regeneration in vivo, and the clinical applications of HA in dentistry, focusing on the mechanism underlining the effect of MW and concentration of HA on cell proliferation and osteogenic differentiation. It is expected that practical progress of HA both in laboratory-based experiments and clinical applications will be achieved in the next few years. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1560-1569, 2016. PMID- 27007719 TI - The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease. AB - Diabetes mellitus (DM) commonly leads to progressive chronic kidney disease despite current best medical practice. The pathogenesis of diabetic kidney disease (DKD) involves a complex network of primary and secondary mechanisms with both intra-renal and systemic components. Apart from inhibition of the renin angiotensin aldosterone system, targeting individual pathogenic mediators with drug therapy has not, thus far, been proven to have high clinical value. Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes through suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise based on their accessibility from adult tissues and their diverse mechanisms of action including secretion of paracrine anti-inflammatory and cyto protective factors. In this review, the progress toward clinical translation of MSC therapy for DKD is critically evaluated. Results from animal models suggest distinct potential for systemic MSC infusion to favourably modulate DKD progression. However, only a few early phase clinical trials have been initiated and efficacy in humans remains to be proven. Key knowledge gaps and research opportunities exist in this field. These include the need to gain greater understanding of in vivo mechanism of action, to identify quantifiable biomarkers of response to therapy and to define the optimal source, dose and timing of MSC administration. Given the rising prevalence of DM and DKD worldwide, continued progress toward harnessing the inherent regenerative functions of MSCs and other progenitor cells for even a subset of those affected has potential for profound societal benefits. PMID- 27007722 TI - Effect of Electronegativity on Bipolar Resistive Switching in a WO3-Based Asymmetric Capacitor Structure. AB - This study investigates the transport and switching time of nonvolatile tungsten oxide based resistive-switching (RS) memory devices. These devices consist of a highly resistive tungsten oxide film sandwiched between metal electrodes, and their RS characteristics are bipolar in the counterclockwise direction. The switching voltage, retention, endurance, and switching time are strongly dependent on the type of electrodes used, and we also find quantitative and qualitative evidence that the electronegativity (chi) of the electrodes plays a key role in determining the RS properties and switching time. We also propose an RS model based on the role of the electronegativity at the interface. PMID- 27007723 TI - Private general paediatric care availability in Melbourne. AB - Objective The aims of the present study were to determine the actual availability of private general paediatric appointments in the Melbourne metropolitan region for children with non-urgent chronic illnesses and the cost of such care. Methods A 'secret shopper' method was used. Telephone calls were made to a random sample of 47 private paediatric clinics. A trained research assistant posed as a parent, requesting the first available appointment with a specific paediatrician. Data regarding appointment availability, total potential charges and net charges after the Medicare rebate were collected. Results Appointments were available in 79% (n=37) of clinics, with 72% (n=34) able to offer an appointment with the requested general paediatrician. The number of days until available appointments varied from same day appointments to a wait of 124 days, with an average wait of 33 days. Of practices that provided information about the appointment cost (n=42), five bulk-billed for the consultation, whereas the remainder (n=37) were fee-paying clinics. The potential maximum charge for an initial consultation in the fee-paying clinics ranged from A$177 to A$430, with an average cost of A$279. The potential maximum out-of-pocket cost for patients ranged from A$40 to A$222, with an average out-of-pocket cost of A$128. Conclusions Private paediatric care in the Melbourne metropolitan region is generally available. The out-of-pocket cost of private paediatric out-patient care may present a potential economic barrier for some families. What is known about the topic? In Australia, out-of pocket expenses for private specialist care are not covered by private health insurance. There are no data available on the actual cost of private paediatric consultations that are based on real-time assessments. Data collected in 1998 suggested that the average waiting time for a first standard consultation with a general paediatrician in a private room was 14.1 days. There are no recent empirical data on appointment availability and waiting time for appointments with general paediatricians in Australia. What does this paper add? There is high availability of paediatric consultations in the private sector. Waiting times for an appointment vary considerably from same day appointments to a wait of 124 days, with an average wait of 33 days. The cost of a private paediatric consultation in Australia to the patient is considerable, with an average potential maximum up-front charge for an initial consultation of A$279 and an average potential maximum out-of-pocket cost of A$128. What are the implications for practitioners? Data on the availability and cost of private paediatric consultations are imperative to formulate evidence-informed policy and better understand variations in the availability of public and private care. PMID- 27007724 TI - Evaluation of the LigaSure(TM) Vessel Sealing System for bowel transection and intestinal anastomosis-an experimental study in a porcine model. AB - BACKGROUND: The purpose of the present study is to assess the value of the LigaSureTM Vessel Sealing System (LVSS) as a means for bowel transection and intestinal anastomosis. METHODS: We compared the LVSS for (1) transecting bowel and (2) creation of an intestinal anastomosis with standard methods such as stapler (S) and hand-sewn (HS) in a porcine model. For each study arm, i.e., bowel transection and anastomosis creation, both the small bowel and colon were examined. In total, ten transections and ten anastomoses were performed for each. Burst and anastomotic leak pressures were compared. RESULTS: In the study arm 1, LVSS achieved lowest burst pressures in both small bowel (LVSS 39.8 +/- 3.6 mmHg, S 81.9 +/- 3.9, HS 111.9 +/- 14.7 mmHg, p < 0.0001) and colon transections (LVSS 21.5 +/- 2.6 mmHg, S 79.5 +/- 4.9, HS 91.0 +/- 5.2 mmHg, p < 0.0001). There was no difference in burst pressures between S and HS in both small bowel and colon transections. In the study arm 2, LVSS showed the lowest anastomotic leak pressures for small bowel (LVSS 26.4 +/- 2.6 mmHg, S 52.1 +/- 6.2, HS 87.4 +/- 7.0 mmHg, p < 0.0001) and colonic anastomoses (LVSS 16.9 +/- 1.3 mmHg, S 55.9 +/- 4.3, HS 74.4 +/- 4.4 mmHg, p < 0.0001). Furthermore, small bowel and colonic anastomoses using S demonstrated significantly lower leak pressures than HS anastomosis p < 0.001 and p = 0.004, respectively. CONCLUSIONS: The LVSS achieves significantly lower burst pressures and anastomotic leak pressures for bowel transection and intestinal anastomosis than S and HS techniques. However, due to the achieved pressure levels of 39.8 +/- 3.6 mmHg, LVSS appears to be a sufficient stand-alone method for bowel transection. Whether it can be used to perform intestinal anastomosis warrants further research in a survival model. PMID- 27007725 TI - Parental Self-Efficacy and Positive Contributions Regarding Autism Spectrum Condition: An Actor-Partner Interdependence Model. AB - Couples affect each other cognitively, emotionally and behaviorally. The goal of this study is to test the benefits and potential use of the actor-partner interdependence model in examining how parental self-efficacy and positive contributions of fathers and mothers of children with Autism Spectrum Condition influence each other's psychological adaptation. The sample includes 76 Spanish couples who completed validated questionnaires measuring predictors, i.e., self efficacy and positive contributions, and adaptation outcomes i.e., stress, anxiety, depression and psychological well-being. Multilevel analysis revealed many actor and some partner effects of parental self-efficacy and positive contributions to be important determinants of adaptation above and beyond child and sociodemographic factors, and as such, these effects should be targeted in clinical intervention programs. PMID- 27007726 TI - The Effect of Parenting Style on Social Smiling in Infants at High and Low Risk for ASD. AB - This study examined how parenting style at 9 months predicts growth in infant social engagement (i.e., social smiling) between 9 and 18 months during a free play interaction in infants at high (HR-infants) and low (LR-infants) familial risk for autism spectrum disorder (ASD). Results indicated that across all infants, higher levels of maternal responsiveness were concurrently associated with higher levels of social smiling, while higher levels of maternal directiveness predicted slower growth in social smiling. When accounting for maternal directiveness, which was higher in mothers of HR-infants, HR-infants exhibited greater growth in social smiling than LR-infants. Overall, each parenting style appears to make a unique contribution to the development of social engagement in infants at high- and low-risk for ASD. PMID- 27007727 TI - What are the needs of adolescents and young adults after a cancer treatment? A Delphi study. AB - Advances in the early detection of cancer and the development of more effective treatments have resulted in a larger number of adolescents and young adults (AYAs), becoming cancer survivors. However, knowledge regarding their needs and if those needs are adequately addressed remains limited. The aims of this study were to: (1) better understand the needs of AYAs after cancer treatment; (2) analyse the importance of those needs; (3) determine which needs are not adequately addressed; and (4) test the hypothesis that AYA cancer survivors have different needs than adult survivors. Twenty-nine health oncology professionals, 17 AYA survivors and 12 relatives of AYA survivors participated in the Delphi study. The needs identified could be classified into six categories, and all were rated as highly important by all participants. The category perceived as least adequately addressed across the three groups was 'Counselling and psychological support.' The findings provide important new information regarding the needs of AYA cancer survivors that can inform the development of interventions to improve the quality of life of these individuals. PMID- 27007728 TI - Arthroscopic Treatment of Traumatic Hip Dislocation. AB - Traumatic hip dislocations are high-energy injuries that often result in considerable morbidity. Although appropriate management improves outcomes, associated hip pathology may complicate the recovery and lead to future disability and pain. Historically, open reduction has been the standard of care for treating hip dislocations that require surgical intervention. The use of hip arthroscopy to treat the sequelae and symptoms resulting from traumatic hip dislocations recently has increased, however. When used appropriately, hip arthroscopy is a safe, effective, and minimally invasive treatment option for intra-articular pathology secondary to traumatic hip dislocation. PMID- 27007729 TI - Ten Years of Medicinal Chemistry (2005-2014) in the Journal of Medicinal Chemistry: Country of Contributors, Topics, and Public-Private Partnerships. AB - This review analyzes the articles that have appeared during the past 10 years in the Journal of Medicinal Chemistry, the leading journal in the field of medicinal chemistry, to provide a picture of the changing trends in this research area. Our analysis involved the country of the corresponding author, assuming that he/she was the leader of the research group, the interaction between private and public sectors, and the research topics. This analysis provides information on the contributions to the journal of authors from each country and highlights the differences between the public and private sectors regarding the research topics pursued. Moreover, changes in the number of articles that describe work on hits, leads, or clinical candidates during these years have been correlated with the affiliation of the contributors (public or private). An analysis of top-cited articles that have appeared in the journal has also been included. The data will provide the basis for understanding the evolution that is taking place in medicinal chemistry. PMID- 27007730 TI - Agricultural Compounds in Water and Birth Defects. AB - Agricultural compounds have been detected in drinking water, some of which are teratogens in animal models. The most commonly detected agricultural compounds in drinking water include nitrate, atrazine, and desethylatrazine. Arsenic can also be an agricultural contaminant, although arsenic often originates from geologic sources. Nitrate has been the most studied agricultural compound in relation to prenatal exposure and birth defects. In several case-control studies published since 2000, women giving birth to babies with neural tube defects, oral clefts, and limb deficiencies were more likely than control mothers to be exposed to higher concentrations of drinking water nitrate during pregnancy. Higher concentrations of atrazine in drinking water have been associated with abdominal defects, gastroschisis, and other defects. Elevated arsenic in drinking water has also been associated with birth defects. Since these compounds often occur as mixtures, it is suggested that future research focus on the impact of mixtures, such as nitrate and atrazine, on birth defects. PMID- 27007731 TI - Characterization of iodinated disinfection by-products in chlorinated and chloraminated waters using Orbitrap based gas chromatography-mass spectrometry. AB - Recent developments in gas chromatography (GC)-mass spectrometry (MS) have opened up the possibility to use the high resolution-accurate mass (HRAM) Orbitrap mass analyzer to further characterize the volatile and semivolatile fractions of environmental samples. This work describes the utilization of GC Orbitrap MS technology to characterize iodine-containing disinfection by-products (iodo-DBPs) in chlorinated and chloraminated DBP mixture concentrates. These DBP mixtures were generated in lab-scale disinfection reactions using Llobregat river water and solutions containing Nordic Lake natural organic matter (NOM). The DBPs generated were concentrated using XAD resins, and extracts obtained were analyzed in full scan mode with the GC Orbitrap MS. Integration of high resolution accurate mass information and fragment rationalization allowed the characterization of up to 11 different iodo-DBPs in the water extracts analyzed, including one new iodo-DBP reported for the first time. Overall, formation of iodo-DBPs was enhanced during chloramination reactions. As expected, NOM characteristics and iodide and bromide content of the tested waters affected the amount and type of iodo-DBPs generated. PMID- 27007732 TI - Multiarray on a test strip (MATS): rapid multiplex immunodetection of priority potato pathogens. AB - Multiarray on a test strip (MATS) was developed for the detection of eight important potato pathogens. The proposed assay combines the rapidity of immunochromatography with the high throughput of array techniques. The test zone of the immunochromatographic strip comprises ordered rows of spots containing antibodies specific for different potato pathogens. The assay benefits from the simplicity of immunochromatography; colored immune complexes form at the corresponding spots within the test zone. The presence and intensity of the coloration are used for identification of the target pathogens. The MATS was applied to the simultaneous detection of eight priority potato pathogens, characterized by the following limits of detection: 1 ng/mL for potato virus X and the ordinary type of potato virus Y, 10 ng/mL for potato virus M, 20 ng/mL for potato leaf roll virus, 40 ng/mL for necrotic-type potato virus Y, 100 ng/mL for potato virus S, 300 ng/mL for potato virus A, and 10(4) cells/mL for Clavibacter michiganensis subsp. sepedonicus. Analysis time was 15 min. The observed sensitivity of the MATS was comparable to the traditional enzyme-linked immunosorbent assay. The developed technique was tested on potato leaf extracts, and its efficiency for on-site control of the pathogens was confirmed in 100 % by commercial LFIA test strips. Graphical abstract Location of binding zones in the developed multiarray on a test strip (MATS) for simultaneous detection of eight pathogens. PMID- 27007733 TI - First report on hemoglobin electrostatic immobilization on WO3 nanoparticles: application in the simultaneous determination of levodopa, uric acid, and folic acid. AB - This work describes the first report about the simultaneous determination of levodopa (L-DOPA) with folic acid (FA) and uric acid (UA) based on electrocatalytic oxidation of L-DOPA with peroxidase properties of hemoglobin (Hb) in the presence of H2O2 as Hb activator. Bovine Hb was electrostatically immobilized on WO3 nanoparticles (WO3NPs) in pH between Hb and WO3NP isoelectric points, and subsequently, a carbon paste electrode (CPE) was modified with the obtained WO3NPs-Hb and multiwalled carbon nanotubes (MWCNTs). The resulting biosensor supplied a sensitive and suitably stable biosensor for the simultaneous determination of L-DOPA, UA, and FA. The obtained linear range and detection limit for L-DOPA, UA, and FA were completely acceptable, and the biosensor response time for these molecules was relatively short so that it reaches about 95 % of its maximum response in less than 10 s. The applicability of the current biosensor was confirmed with the determination of L-DOPA in the presence of fixed amounts of FA and UA in some real samples by the standard addition method. PMID- 27007734 TI - Use of primary literature in the undergraduate analytical class. PMID- 27007735 TI - A Raman "spectroscopic clock" for bloodstain age determination: the first week after deposition. AB - Knowing the time since deposition (TSD) of an evidentiary bloodstain is highly desired in forensics, yet it can be extremely complicated to accurately determine in practice. Although there have been numerous attempts to solve this problem using a variety of different techniques, currently, no established, well-accepted method exists. Here, a Raman spectroscopic approach was developed for determining the age of bloodstains up to 1 week old. Raman spectroscopy, along with two dimensional correlation spectroscopy (2D CoS) and statistical modeling, was used to analyze fresh bloodstains at ten time points under ambient conditions. The 2D CoS results indicate a high correlation between several Raman bands and the age of a bloodstain. A regression model was built to provide quantitative predictions of the TSD, with cross-validated root mean squared error and R (2) values of 0.13 and 0.97, respectively. It was determined that a "new" (1 h) bloodstain could be easily distinguished from older bloodstains, which is very important for forensic science in helping to establish the relevant association of multiple bloodstains. Additionally, all bloodstains were confirmatively identified as blood by comparing the experimentally measured spectra to multidimensional body fluid spectroscopic signatures of blood, saliva, semen, sweat, and vaginal fluid. These results demonstrate that Raman spectroscopy can be used as a nondestructive analytical tool for discriminating between bloodstains on the scale of hours to days. This approach shows promise for immediate practical use in the field to predict the TSD with a high degree of accuracy. Graphical Abstract Bloodstain aging over time illustrating naturally ocurring processes. PMID- 27007736 TI - Liquid chromatography-mass spectrometry as a general approach for investigating covalent binding of drugs to DNA. AB - This paper aims at developing a general strategy to study the detection of adducts of drugs with DNA. In particular, ethacrynic acid has been chosen as a model reactive drug that could be able to bind covalently to DNA bases. Such interactions were detected by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Principal component analysis (PCA) was applied as an unsupervised method to try to find the potential candidate adduct from MS features. The occurrence of adducts was investigated preliminarily using deoxynucleosides of the guanine, cytosine, adenine, and thymine separately as a way to optimize both separation and detection conditions. Interpretations of MS and MS/MS spectra provided tentative structures of the compounds formed. Conclusions extracted from such simple nucleoside models were further extended to the analysis of DNA adducts. For such a purpose, DNA was incubated in the presence of ethacrynic acid under appropriate experimental conditions and its further enzymatic hydrolysis released the corresponding nucleosides. UHPLC-MS analysis of the resulting test samples under the SRM detection mode confirmed the presence of ethacrynic acid derivatives of nucleosides occurring at very low concentration levels, thus proving the overall performance of the method. Graphical Abstract General approach for investigating drug-DNA adduct formation. PMID- 27007737 TI - Mn(2+)-doped NaYF4:Yb/Er upconversion nanoparticle-based electrochemiluminescent aptasensor for bisphenol A. AB - A novel aptasensor labeled with Mn(2+)-doped NaYF4:Yb/Er upconversion nanoparticles (NaYF4:Yb,Er/Mn UCNPs) was employed in electrogenerated chemiluminescence (ECL) for the sensitive detection of bisphenol A (BPA). The ECL aptasensor was assembled by immobilizing the thiolated aptamers of BPA covalently on a gold nanoparticle (AuNPs)-modified electrode and pairing with complementary DNA labeled with NaYF4:Yb,Er/Mn UCNPs. The ECL aptasensor can not only rapidly and accurately detect BPA concentrations from 0.05 to 100 ng/mL with a detection limit of 0.037 ng/mL but also provides a new platform for ECL applications based on the use of upconversion nanoparticles as a promising alternative material. Graphical Abstract The NaYF4:Yb,Er/Mn UCNPs combining with the BPA aptamer serving as recognition elements create a ECL platform for the sensitive detection of bisphenol A. The change in ECL signals induced by aptamer-target interactions was measured and a significant decrease in intensity was found on interaction with BPA in the concentration range of 0.05 to 100 ng/mL. PMID- 27007738 TI - Dosage- and time-dependent antibacterial effect of zinc oxide nanoparticles determined by a highly uniform SERS negating undesired spectral variation. AB - Massive production of nanomaterials poses a high risk to environmental ecology and human health. However, comprehensive understanding of nanotoxicity is still a major challenge due to the limitations of assessment methods, especially at the molecular level. We developed a new, sensitive, and robust fingerprinting surface enhanced Raman spectroscopy (SERS) approach to interrogate both dose- and time dependent phenotypic bacterial responses to zinc oxide nanoparticles (ZnO NPs). SERS enhancement was provided by biocompatible Au NPs. Additionally, a novel vacuum filtration-based strategy was adopted to fabricate bacterial samples with highly uniform SERS signals, ensuring the acquisition of robust and independent spectral changes from ZnO NPs-impacted bacteria without undesirable spectral variations. Combined with multivariate analysis, clear and informative spectral alteration profiles were obtained. Much greater alterations were found in low dose ranges than high-dose ranges, indicating a reduction in the bioavailability of ZnO NPs with doses. Time-resolved bacterial responses provided important information on toxic dynamics, i.e., rapid action of ZnO NPs within 0.5 h was identified, and ZnO NPs at low doses and long exposure time exerted similar effects to high doses, indicating the concerns associated with low-dose exposure. Further analysis of biochemical changes revealed metabolic activity decrease over both incubation time and doses. Meanwhile, a short-term protection strategy of bacteria by producing lipid-containing outer membrane vesicles to mitigate the cell of toxic NPs was suggested. Finally, Zn(2+) ions released from NPs were demonstrated to be irrelevant to bacterial responses on both dose and time scales. The new SERS methodology can potentially profile a large variety of toxic NPs and advance our understanding of nanotoxicity. Graphical Abstract A highly uniform SERS signal of bacteria negating undesired spectral variation via a novel vacuum filtration-based strategy, combined with multivariate PCA-LDA analysis, was utilized to interrogate both dose- and time-dependent antibacterial effect of zinc oxide nanoparticles, and can be extended to a variety of other toxic nanoparticles. PMID- 27007739 TI - EC-QCL mid-IR transmission spectroscopy for monitoring dynamic changes of protein secondary structure in aqueous solution on the example of beta-aggregation in alcohol-denaturated alpha-chymotrypsin. AB - In this work, a novel EC-QCL-based setup for mid-IR transmission measurements in the amide I region is introduced for monitoring dynamic changes in secondary structure of proteins. For this purpose, alpha-chymotrypsin (aCT) acts as a model protein, which gradually forms intermolecular beta-sheet aggregates after adopting a non-native alpha-helical structure induced by exposure to 50 % TFE. In order to showcase the versatility of the presented setup, the effects of varying pH values and protein concentration on the rate of beta-aggregation were studied. The influence of the pH value on the initial reaction rate was studied in the range of pH 5.8-8.2. Results indicate an increased aggregation rate at elevated pH values. Furthermore, the widely accessible concentration range of the laser based IR transmission setup was utilized to investigate beta-aggregation across a concentration range of 5-60 mg mL(-1). For concentrations lower than 20 mg mL( 1), the aggregation rate appears to be independent of concentration. At higher values, the reaction rate increases linearly with protein concentration. Extended MCR-ALS was employed to obtain pure spectral and concentration profiles of the temporal transition between alpha-helices and intermolecular beta-sheets. Comparison of the global solutions obtained by the modelled data with results acquired by the laser-based IR transmission setup at different conditions shows excellent agreement. This demonstrates the potential and versatility of the EC QCL-based IR transmission setup to monitor dynamic changes of protein secondary structure in aqueous solution at varying conditions and across a wide concentration range. Graphical abstract EC-QCL IR spectroscopy for monitoring protein conformation change. PMID- 27007740 TI - Nanocrystalline diamond sensor targeted for selective CRP detection: an ATR-FTIR spectroscopy study. AB - Protein immobilization on functionalized fluorine-terminated nanocrystalline (NCD) films was studied by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy using an immobilization protocol developed to specifically bind C-reactive protein (CRP). Using an ATR-FTIR spectroscopy method employing a force-controlled anvil-type configuration, three critical steps of the ex situ CRP immobilization were analyzed. First, the NCD surface was passivated by deposition of a copolymer layer consisting of polyethylene oxide and polypropylene oxide. Second, a synthetic modified polypeptide binder with high affinity to CRP was covalently attached to the polymeric film. Third, CRP dissolved in aqueous buffer in concentrations of 10-20 MUg/mL was added on the functionalized NCD surface. Both the amide I and II bands, due to the polypeptide binder and CRP, were clearly observed in ATR-FTIR spectra. CRP amide I bands were extracted from difference spectra and yielded bands that agreed well with the reported amide I band of free (non-bonded) CRP in solution. Thus, our results show that CRP retains its secondary structure when it is attached to the polypeptide binders. Compared to previous IR studies of CRP in solution, about 200 times lower concentration was applied in the present study. Graphical Abstract Direct non-destructive ATR-FTIR analysis of C-reactive protein (CRP) selectively bound to functionalized nanocrystalline diamond (NCD) sensor surface. PMID- 27007741 TI - Polysaccharide Encrusted Multilayered Nano-Colloidal System of Andrographolide for Improved Hepatoprotection. AB - Andrographolide (AP), a phytoconstituent of Andrographis paniculata is reported as a potent hepatoprotective agent. However, utility of this molecule is restricted due to its low aqueous solubility, gastric instability and hence low bioavailability. It was aimed to formulate and characterize AP-loaded, natural biopolymer stabilized, multilayered nano-hydrocolloid delivery system. Nanoemulsion (NE) was formulated using layer-by-layer (LbL) technology via electrostatic deposition of chitosan over alginate encrusted o/w NE by ultra sonication. Improved transparency and stability of NE were observed with increasing sonication time. Best stability was obtained after 20 min sonication and particle size of the multilayered NE was measured in the range of 90.8-167.8 nm. Transmission electron microscopy confirmed the progressive layering of nanosized NE. Higher magnitude of zeta potential (i.e., 22.9 to 31.01 mV) confirmed higher stability and coating of alginate layer over NE surface for the period of 3 months. NE showed strategic release pattern when assessed in vitro in various simulated biological fluids of GIT in timed pattern. Multilayered NE showed significant modulation in liver function test (ALT, ALP, AST, TBIL, DBIL, and liver glycogen) and serum cytokines (TNF-alpha, IL-6, IL-10, and IL-beta) when assessed in vivo in galactosamine-lipopolysaccharide intoxicated mice. In conclusion, the andrographolide engrained multi-layered NE enhanced the solubility, stability and henceforth assured the increased availability in simulated biological fluids. The in vivo study exhibited the significantly improved hepatoprotection by andrographolide when delivered in stable multi layered NE carrier systems. PMID- 27007742 TI - Comparative Evaluation of Nimesulide-Loaded Nanoparticles for Anticancer Activity Against Breast Cancer Cells. AB - Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(epsilon caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation. Nanoparticles were evaluated with respect to the entrapment efficiency, size characteristics, drug release rates, thermal behavior, cell viability assays, and apoptosis. The resulting nanoparticles were found to be spherical shapes with negative surface charges. The average diameter of all nanoparticles ranged between 148.5 and 307.2 nm. In vitro release profiles showed that all nanoparticles exhibited a biphasic release pattern. NMS-loaded PEG-b-PCL nanoparticles demonstrated significant anticancer activity against MCF-7 breast cancer cells in a dose-dependent manner, and the effects of nanoparticles on cell proliferation were significantly affected by the preparation techniques. The nanoparticles developed in this work displayed higher potential for the NMS delivery against breast cancer treatment for the future. PMID- 27007743 TI - Highly efficient and reusable CNT supported iron(ii) catalyst for microwave assisted alcohol oxidation. AB - The highly efficient eco-friendly synthesis of ketones (yields over 99%) from secondary alcohols is achieved by combination of [FeCl2{eta(3)-HC(pz)3}] (pz = pyrazol-1-yl) supported on functionalized multi-walled carbon nanotubes and microwave irradiation, in a solvent-free medium. The carbon homoscorpionate iron(ii) complex is the first one of this class to be used as catalyst for the oxidation of alcohols. PMID- 27007744 TI - Understanding the Dispersion and Assembly of Bacterial Cellulose in Organic Solvents. AB - The constituent nanofibrils of bacterial cellulose are of interest to many researchers because of their purity and excellent mechanical properties. Mechanisms to disrupt the network structure of bacterial cellulose (BC) to isolate bacterial cellulose nanofibrils (BCN) are limited. This work focuses on liquid-phase dispersions of BCN in a range of organic solvents. It builds on work to disperse similarly intractable nanomaterials, such as single-walled carbon nanotubes, where optimum dispersion is seen for solvents whose surface energies are close to the surface energy of the nanomaterial; bacterial cellulose is shown to disperse in a similar fashion. Inverse gas chromatography was used to determine the surface energy of bacterial cellulose, under relevant conditions, by quantifying the surface heterogeneity of the material as a function of coverage. Films of pure BCN were prepared from dispersions in a range of solvents; the extent of BCN exfoliation is shown to have a strong effect on the mechanical properties of BC films and to fit models based on the volumetric density of nanofibril junctions. Such control offers new routes to producing robust cellulose films of bacterial cellulose nanofibrils. PMID- 27007745 TI - Preliminary studies for the development of intranasal nanoemulsion containing CNS agent: emphasizing the utilization of cut and weigh method. AB - CONTEXT: The selection of excipients and preformulation strategy plays a vital role for the development of nanoemulsion, due to anatomical and physiological challenges posed by nasal cavity. OBJECTIVE: This attempt is focused on the selection and optimization of excipients for the development of a nanoemulsion system for intranasal delivery. MATERIALS AND METHODS: Excipients were selected on the basis of solubility of active drug, compatibility interactions and nasal irritancy. Surfactant and co-surfactant combination and their ratio were finalized on the basis of nanoemulsion region obtained from constructed phase diagrams with Capmul MCM as oil phase. A validated cut and weigh method was employed for the optimization of different phase diagrams with respect to nanoemulsion region. RESULTS AND DISCUSSION: The solubility of drug in Capmul MCM, Labrasol, and Transcutol-P was found to be superior with numeric values of 79.50 +/- 1.68 mg/ml, 51.10 +/- 1.39 mg/ml, and 36.60 +/- 0.85 mg/ml, respectively. On the basis of phase diagram analysis, Labrasol and Transcutol-P in 3:1 ratio provides greater nanoemulsion region of 65.28 +/- 0.18%. The validation of cut and weigh method revealed that there was no significant statistical difference (P > 0.05) with a %RSD value of 2.38 for intersheet variation. CONCLUSION: The results of validation studies for cut and weigh method suggests that it can be effectively used as an optimization method for the selection of nanoemulsion composition. PMID- 27007746 TI - Exploring the climates of undergraduate professionalism in a Saudi and a UK medical school. AB - AIM: To explore the usefulness of an online inventory for tracking medical students' understanding of the importance of lapses in academic integrity. METHOD: Respondents were asked to recommend sanctions for lapses as a proxy of their understanding of the importance of the 34 types of poor professionalism. RESULTS: The data suggest that while there is congruence, there are also substantial differences between ratings of the importance of poor professionalism, particularly in relation to data integrity, between a cohort in Saudi Arabia and one in the UK. CONCLUSION: This resource may be useful both for teaching and learning in individual schools, and particularly for the induction of doctors into organisational environments different from the one they were trained in. PMID- 27007748 TI - Short-Term Synaptic Plasticity Regulation in Solution-Gated Indium-Gallium-Zinc Oxide Electric-Double-Layer Transistors. AB - In the biological nervous system, synaptic plasticity regulation is based on the modulation of ionic fluxes, and such regulation was regarded as the fundamental mechanism underlying memory and learning. Inspired by such biological strategies, indium-gallium-zinc-oxide (IGZO) electric-double-layer (EDL) transistors gated by aqueous solutions were proposed for synaptic behavior emulations. Short-term synaptic plasticity, such as paired-pulse facilitation, high-pass filtering, and orientation tuning, was experimentally emulated in these EDL transistors. Most importantly, we found that such short-term synaptic plasticity can be effectively regulated by alcohol (ethyl alcohol) and salt (potassium chloride) additives. Our results suggest that solution gated oxide-based EDL transistors could act as the platforms for short-term synaptic plasticity emulation. PMID- 27007747 TI - Role of Brain-Derived Neurotrophic Factor in Beneficial Effects of Repetitive Transcranial Magnetic Stimulation for Upper Limb Hemiparesis after Stroke. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) can improve upper limb hemiparesis after stroke but the mechanism underlying its efficacy remains elusive. rTMS seems to alter brain-derived neurotrophic factor (BDNF) and such effect is influenced by BDNF gene polymorphism. OBJECTIVES: To investigate the molecular effects of rTMS on serum levels of BDNF, its precursor proBDNF and matrix metalloproteinase-9 (MMP-9) in poststroke patients with upper limb hemiparesis. METHODS: Poststroke patients with upper limb hemiparesis were studied. Sixty-two patients underwent rehabilitation plus rTMS combination therapy and 33 patients underwent rehabilitation monotherapy without rTMS for 14 days at our hospital. One Hz rTMS was applied over the motor representation of the first dorsal interosseous muscle on the non-lesional hemisphere. Fugl-Meyer Assessment and Wolf Motor Function (WMFT) were used to evaluate motor function on the affected upper limb before and after intervention. Blood samples were collected for analysis of BDNF polymorphism and measurement of BDNF, proBDNF and MMP-9 levels. RESULTS: Two-week combination therapy increased BDNF and MMP-9 serum levels, but not serum proBDNF. Serum BDNF and MMP-9 levels did not correlate with motor function improvement, though baseline serum proBDNF levels correlated negatively and significantly with improvement in WMFT (rho = -0.422, p = 0.002). The outcome of rTMS therapy was not altered by BDNF gene polymorphism. CONCLUSIONS: The combination therapy of rehabilitation plus low-frequency rTMS seems to improve motor function in the affected limb, by activating BDNF processing. BDNF and its precursor proBDNF could be potentially suitable biomarkers for poststroke motor recovery. PMID- 27007749 TI - Dual Bone Fixation: A Biomechanical Comparison of 3 Implant Constructs in a Mid Diaphyseal Fracture Model of the Feline Radius and Ulna. AB - OBJECTIVE: To compare the biomechanical properties of dual bone fixation (DBF) constructs to radial locking compression plating (LCP) in an ex vivo feline antebrachial fracture gap model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Cadaveric feline antebrachii (n=12 pairs). METHODS: Antebrachii were radiographed to confirm normal skeletal appearance and maturity. After creation of a 5 mm radial and ulnar ostectomy, each antebrachium received 1 of 3 constructs using an incomplete randomized block design (n=8 per group). All groups received a 10 hole 2.0 mm radial LCP. DBF groups received either a 1.2 mm ulnar intramedullary pin (LCP with pin) or an 8 hole 2.0 mm ulnar LCP in addition to the radial LCP. Biomechanical testing was performed in axial compression and caudocranial and mediolateral 4-point bending before destruction in axial compression. RESULTS: DBF constructs (LCP with pin and dual LCP) were significantly stiffer than radial LCP alone in axial compression and caudocranial bending. There were no differences between LCP with pin and dual LCP constructs in axial compression and caudocranial bending or between any constructs in mediolateral bending. Failure load was significantly greater for dual LCP than LCP with pin or LCP alone constructs. Failure loads were not different between LCP with pin and LCP alone. CONCLUSION: DBF significantly increased construct stiffness and strength. Given the high complication rate reported in cat antebrachial fractures when only the radius is stabilized, surgeons should consider DBF. PMID- 27007750 TI - Severe rhabdomyolysis and acute kidney injury associated with methoxphenidine. PMID- 27007752 TI - Driving with music: cognitive-behavioural implications. PMID- 27007751 TI - Gold-Mediated Exfoliation of Ultralarge Optoelectronically-Perfect Monolayers. AB - Gold-mediated exfoliation of ultralarge optoelectronically perfect monolayers with lateral dimensions up to ~500 MUm is reported. Electrical, optical, and X ray photo-electron spectroscopy characterization show that the quality of the gold-exfoliated flakes is similar to that of tape-exfoliated flakes. Large-area flakes allow manufacturing of large-area mono-layer transition metal dichalcogenide electronics. PMID- 27007753 TI - Quantitative Light-induced Fluorescence-Digital as an oral hygiene evaluation tool to assess plaque accumulation and enamel demineralization in orthodontics. AB - OBJECTIVE: To assess the use of Quantitative Light-induced Fluorescence-Digital as an oral hygiene evaluation tool during orthodontic treatment. MATERIALS AND METHODS: In this prospective, randomized clinical trial, 33 patients undergoing fixed orthodontic appliance treatment were randomly allocated to receive oral hygiene reinforcement at four consecutive appointments using either white light (WL) or Quantitative Light-induced Fluorescence-Digital (QLF) images, taken with a device, as visual aids. Oral hygiene was recorded assessing the QLF images for demineralization, by fluorescence loss (DeltaF), and plaque coverage (DeltaR30). A debriefing questionnaire ascertained patient perspectives. RESULTS: There were no significant differences in demineralization (P = .56) or plaque accumulation (P = .82) between the WL and QLF groups from T0 to T4. There was no significant reduction in demineralization, DeltaF, in the WL, or the QLF group from T0-T4 (P > .05); however, there was a significant reduction in DeltaR30 plaque scores (P < .05). All the participants found being shown the images helpful, with 100% of the QLF group reflecting that it would be useful to have oral hygiene reinforcement for the full duration of treatment compared with 81% of the WL group (OR 2.3; P < .05). CONCLUSIONS: Quantitative Light-induced Fluorescence-Digital can be used to detect and monitor demineralization and plaque during orthodontics. Oral hygiene reinforcement at consecutive appointments using WL or QLF images as visual aids is effective in reducing plaque coverage. In terms of clinical benefits, QLF and WL images are of similar effectiveness; however, patients preferred the QLF images. PMID- 27007754 TI - Evaluation of mandibular volume classified by vertical skeletal dimensions with cone-beam computed tomography. AB - OBJECTIVE: To investigate the relationship between anteroposterior and vertical differences in maxillofacial morphology and mandibular volume. MATERIALS AND METHODS: Subjects comprised 213 Japanese adults (84 males and 129 females) who were divided into three groups based on mandibular basal arch (ANB) and Wits, measured in a cephalometric analysis: Class I (-1 degrees <= ANB < 4 degrees ,-1 mm <= Wits < 0 mm), Class II (ANB >= 4 degrees , Wits >= 0), and Class III (ANB < 1 degrees , Wits <-1 mm). Subjects were also divided into three groups based on the mandibular plane angle (Mp), as follows: hypodivergent (Mp < 23 degrees ), normodivergent (Mp = 23-30 degrees ), and hyperdivergent (Mp > 30 degrees ) groups. Mandibular volume was measured from cone-beam computed tomographic images that were analyzed using AnalyzeTM image processing software and compared among the three groups in each classification. RESULTS: No significant differences were noted in mandibular volume among Classes I, II, and III. An inverse relationship was found between mandibular volume and Mp, and a significant difference was noted in mandibular volume between the hypodivergent and hyperdivergent groups. CONCLUSIONS: In addition to two-dimensional analysis, such as lateral cephalometry, three-dimensional information such as volume, provided by cone-beam computed tomography, contributes to a more detailed assessment of maxillofacial morphology. PMID- 27007755 TI - Velopharyngeal changes after maxillary distraction in cleft patients using a rigid external distraction device: A retrospective study. AB - OBJECTIVE: To evaluate early and late velopharyngeal changes in cleft lip and palate (CLP) patients after use of the Rigid External Distractor (RED) device and to correlate these changes to the amount of maxillary advancement. MATERIALS AND METHODS: Thirty Class III CLP patients were included in the study. Maxillary advancement was performed using the RED device in combination with titanium miniplates and screws for anchorage. Lateral cephalograms, nasometer, and nasopharyngoscope records were taken before distraction, immediately after distraction, and 1 year after distraction. A paired t-test was used to detect differences at P < .05. RESULTS: SNA angle and A point and ANS to Y axis were significantly increased after maxillary distraction (P = .0001). Statistically significant increases in nasopharyngeal and oropharyngeal depths, velar angle, and need ratio were also found (P = .0001). Nasalance scores showed a significant increase (P = .008 for nasal text and .044 for oral text). A significant positive correlation was observed between the amount of maxillary advancement and the increase in nasopharyngeal depth and hypernasality (P = .012 and .026, respectively). CONCLUSIONS: Nasopharyngeal function was deteriorated after maxillary advancement in CLP patients. There was a significant positive correlation between the amount of maxillary advancement and the increase in nasopharyngeal depth and hypernasality. PMID- 27007756 TI - Systematic reviews: knowledge translation? PMID- 27007757 TI - Therapeutic expectations: Dentistry relies less on dental plaque as a major etiological factor. OR On the dental needs of young orthodontic patients (12-20 years old). AB - In Brazilian cities and states governed efficiently with wealth ethically administered, carious and periodontal diseases have prevalence rates similar to those found in socially developed European countries. This shift in reality, noticed over the last 15 years, reflects on changes in the etiological factors related to patients' major expectations and needs--especially young and orthodontic patients--which turn out to be a result of dental trauma, malocclusion, facial aspect, dental agenesis and iatrogenesis. Under such conditions, patients begin to appreciate the value of tooth position, color and shape, their smile and function: details become relevant. Carious and periodontal diseases remain an issue, not only from a preventive prospect, but also from a curative one. Nevertheless, it should be noted that changes and development are inevitable, and we should be prepared to contribute to the wellbeing of people, particularly regarding their novel needs and expectations. PMID- 27007758 TI - An interview with Hyeon-Shik Hwang. AB - It gives me great pleasure to interview Dr. Hyeon-Shik Hwang, an innovative orthodontist who has developed many creative techniques over his career. Dr. Hwang was born in Korea and received his DDS and PhD degrees from Yonsei University in Seoul. He is professor and chairman of the Department of Orthodontics at Chonnam National University School of Dentistry, Gwangju, Korea. Dr. Hwang, as a faculty at the university hospital, has maintained a successful clinical practice for more than 25 years. He has treated many adult patients focusing on esthetics and periodontal health and has developed many clinical techniques to improve the effectiveness and efficiency of treatment to the benefit of both the patient and practitioner. Dr. Hwang is also interested in the evaluation of facial asymmetry two- and three-dimensionally. As one of the early adopters of cone-beam volume imaging, he has given special emphasis on the management of surgical cases. He is married to Jung-Un Park with whom he has two sons. His favorite hobbies are photography and listening to music. When I was presented to him in a congress, it was a great pleasure meeting someone who I already admired for his singular work. Later on, his humbleness and knowledge made me marvel at him even more. I hope that all readers of Dental Press Journal of Orthodontics also enjoy the teachings from this brilliant Korean orthodontist! Guilherme Thiesen - interview coordinator. PMID- 27007759 TI - Evaluation of upper airways after bimaxillary orthognathic surgery in patients with skeletal Class III pattern using cone-beam computed tomography. AB - INTRODUCTION: It has been suggested that mandibular setback surgery, combined or not with maxillary advancement as a treatment alternative for patients with mandibular prognathism, can induce changes in upper airway space (UAS). Therefore, this study aimed to assess the response of the upper airway in the oropharynx region of patients with Class III skeletal pattern that underwent bimaxillary orthognathic surgery (maxillary advancement and mandibular setback) combined with mentoplasty. MATERIAL AND METHODS: The sample comprised 26 cone beam computed tomography (CBCT) scans of 13 patients. The examination was taken before and after surgery. UAS volume, sagittal area, length and minimal axial area with its width, depth and location, were measured with the aid of Dolphin ImagingTM software version 11.5 Premium. Data were statistically treated by applying Shapiro-Wilk test and Student's paired t-test, considering as statistically significant the results of which p-value was lower than 0.05. RESULTS: No statistically significant differences were found in any measurements evaluated. CONCLUSIONS: No significant changes were observed in the oropharynx after bimaxillary orthognathic surgery and mentoplasty. PMID- 27007760 TI - Deflection test evaluation of different lots of the same nickel-titanium wire commercial brand. AB - INTRODUCTION: The aim of this in vitro study was to compare the elastic properties of the load-deflection ratio of orthodontic wires of different lot numbers and the same commercial brand. METHODS: A total of 40 nickel-titanium (NiTi) wire segments (Morelli OrtodontiaTM--Sorocaba, SP, Brazil), 0.016-in in diameter were used. Groups were sorted according to lot numbers (lots 1, 2, 3 and 4). 28-mm length segments from the straight portion (ends) of archwires were used. Deflection tests were performed in an EMIC universal testing machine with 5 N load cell at 1 mm/minute speed. Force at deactivation was recorded at 0.5, 1, 2 and 3 mm deflection. Analysis of variance (ANOVA) was used to compare differences between group means. RESULTS: When comparing the force of groups at the same deflection (3, 2 and 1 mm), during deactivation, no statistical differences were found. CONCLUSION: There are no changes in the elastic properties of different lots of the same commercial brand; thus, the use of different lots of the orthodontic wires used in this research does not compromise the final outcomes of the load-deflection ratio. PMID- 27007761 TI - Nasal septum changes in adolescent patients treated with rapid maxillary expansion. AB - OBJECTIVE: To analyze cone-beam computed tomography (CBCT) scans to measure changes in nasal septal deviation (NSD) after rapid maxillary expansion (RME) treatment in adolescent patients. METHODS: This retrospective study involved 33 patients presenting with moderate to severe nasal septum deviation as an incidental finding. Out of these 33 patients, 26 were treated for transverse maxillary constriction with RME and seven, who did not undergo RME treatment, were included in the study as control group. CBCT scans were taken before appliance insertion and after appliance removal. These images were analyzed to measure changes in nasal septum deviation (NSD). Analysis of variance for repeated measures (ANOVA) was used. RESULTS: No significant changes were identified in NSD regardless of the application or not of RME treatment and irrespective of the baseline deviation degree. CONCLUSION: This study did not provide strong evidence to suggest that RME treatment has any effect on NSD in adolescent patients; however, the results should be interpreted with caution, due to the small sample size and large variation amongst individual patient characteristics. PMID- 27007762 TI - Frequency of orthodontic extraction. AB - INTRODUCTION: The option of dental extraction for orthodontic purposes has been debated for more than 100 years, including periods when it was widely used in treatment, including the present, during which other methods are used to avoid dental extractions. The objective was to analyze the frequency of tooth extraction treatment performed between 1980 and 2011 at the Orthodontic Clinic of Universidade Estadual do Rio de Janeiro (UERJ). MATERIAL AND METHODS: The clinical records of 1484 patients undergoing orthodontic treatment were evaluated. The frequency of extractions was evaluated with regard to sex, Angle's classification, the different combinations of extractions and the period when orthodontic treatment began. Chi-square test was used to determine correlations between variables, while the chi-square test for trends was used to assess the frequency of extractions over the years. RESULTS: There was a reduction of approximately 20% in the frequency of cases treated with tooth extraction over the last 32 years. The most frequently extracted teeth were first premolars. Patients with Class I malocclusion showed fewer extractions, while Class II patients underwent a higher number of extraction treatment. There were no statistically significant differences with regard to sex. CONCLUSION: New features introduced into the orthodontic clinic and new esthetic concepts contributed to reducing the number of cases treated with dental extractions. However, dental extractions for orthodontic purposes are still well indicated in certain cases. PMID- 27007763 TI - Judging orthodontic treatment complexity. AB - OBJECTIVE: The aim of the present study was to investigate possible relations between anticipated overall treatment complexity (AOTC) of an orthodontic case and malocclusion characteristics. METHODS: Two groups of orthodontists (groups A and B) were asked to define perceived treatment complexity (PTC) of orthodontic cases based on 16 characteristics of malocclusion by means of a questionnaire. Each question was answered on a six-point ordinal scale, with one "not applicable" option (score 0). Group A was also asked to give the AOTC of the specific case on a five-point ordinal scale. The index of orthodontic treatment need (IOTN) score of the specific cases as well as the malocclusion characteristics were assessed by one author. RESULTS: There is a significant relationship between IOTN and AOTC (p< 0.0001), 22% of variability is explained by differences in IOTN. Adding objective characteristics of malocclusion to explain AOTC does not significantly increase the explained variability (p = 0.086). In judging interobserver agreement, a weighted Kappa of 0.60 for group A and 0.56 for group B was found. The weighted Kappa for agreement in AOTC equals 0.06. CONCLUSION: The relation between IOTN and AOTC was found to be significant. Moderate agreement on PTC among observers and a low level agreement regarding AOTC were found in the present study. PMID- 27007764 TI - Evaluation of long-term stability of mesiodistal axial inclinations of maxillary molars through panoramic radiographs in subjects treated with Pendulum appliance. AB - OBJECTIVE: To evaluate the stability of mesiodistal inclination of maxillary molars produced by a pendulum appliance, five years after completion of orthodontic treatment. Angulation changes were compared to an untreated sample. METHODS: The sample consisted of 20 patients (14 females and 6 males) with Class II, Division 1 malocclusion that was treated through molar distalization with a pendulum appliance followed by cervical headgear and full fixed appliances. Maxillary molar inclination was evaluated through panoramic radiograph. The mean age at pretreatment was 14.3 +/- 1.6 years, whereas at immediate post-treatment it was 18.6 +/- 1.8 years, and at long-term post-treatment it was 23.8 +/- 2.0 years. A control group of 16 untreated individuals with untreated normocclusion ranging in age from 12 to 17 years old were used as comparison group. Data were statistically analyzed with independent t-tests and ANOVA test followed by Tukey post-hoc tests. RESULTS: Statistically significant differences were found between T1(94.50) and T2 (98.80) as well as between T2 and T3 (94.70) for maxillary first molars. Maxillary second molars did not show any statistically significant positional changes during the evaluated time periods T1 (107.50), T2 (109.30) and T3 (106.90). CONCLUSION: Although maxillary first molars underwent distal crown inclination immediately after treatment, approximately five years thereafter their roots tended to upright close to the pretreatment positions. PMID- 27007765 TI - Orthodontic intrusion of maxillary incisors: a 3D finite element method study. AB - OBJECTIVE: In orthodontic treatment, intrusion movement of maxillary incisors is often necessary. Therefore, the objective of this investigation is to evaluate the initial distribution patterns and magnitude of compressive stress in the periodontal ligament (PDL) in a simulation of orthodontic intrusion of maxillary incisors, considering the points of force application. METHODS: Anatomic 3D models reconstructed from cone-beam computed tomography scans were used to simulate maxillary incisors intrusion loading. The points of force application selected were: centered between central incisors brackets (LOAD 1); bilaterally between the brackets of central and lateral incisors (LOAD 2); bilaterally distal to the brackets of lateral incisors (LOAD 3); bilaterally 7 mm distal to the center of brackets of lateral incisors (LOAD 4). RESULTS AND CONCLUSIONS: Stress concentrated at the PDL apex region, irrespective of the point of orthodontic force application. The four load models showed distinct contour plots and compressive stress values over the midsagittal reference line. The contour plots of central and lateral incisors were not similar in the same load model. LOAD 3 resulted in more balanced compressive stress distribution. PMID- 27007766 TI - The influence of distal-end heat treatment on deflection of nickel-titanium archwire. AB - OBJECTIVE: The aim of this in vitro study was to evaluate the deflection-force behavior of nickel-titanium (NiTi) orthodontic wires adjacent to the portion submitted to heat treatment. MATERIAL AND METHODS: A total of 106 segments of NiTi wires (0.019 x 0.025-in) and heat-activated NiTi wires (0.016 x 0.022-in) from four commercial brands were tested. The segments were obtained from 80 archwires. For the experimental group, the distal portion of each segmented archwire was subjected to heat treatment (n = 40), while the other distal portion of the same archwire was used as a heating-free control group (n = 40). Deflection tests were performed in a temperature-controlled universal testing machine. Unpaired Student's t-tests were applied to determine if there were differences between the experimental and control groups for each commercial brand and size of wire. Statistical significance was set at p < 0.05. RESULTS: There were no statistically significant differences between the tested groups with the same size and brand of wire. CONCLUSIONS: Heat treatment applied to the distal ends of rectangular NiTi archwires does not permanently change the elastic properties of the adjacent portions. PMID- 27007768 TI - Class II, Division 1 Angle malocclusion with severe proclination of maxillary incisors. AB - Protrusion of maxillary incisors is a common complaint among patients seeking orthodontic treatment. This report addresses the correction of Class II Angle malocclusion with excessively bucally proclined maxillary incisors, in an adolescent female patient, through the use of extraoral and fixed appliances. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as part of the requirements for obtaining the title of certified by the BBO. PMID- 27007767 TI - 3D virtual planning in orthognathic surgery and CAD/CAM surgical splints generation in one patient with craniofacial microsomia: a case report. AB - OBJECTIVE: In this case report, the feasibility and precision of tridimensional (3D) virtual planning in one patient with craniofacial microsomia is tested using Nemoceph 3D-OS software (Software Nemotec SL, Madrid, Spain) to predict postoperative outcomes on hard tissue and produce CAD/CAM (Computer Aided Design/Computer Aided Manufacturing) surgical splints. METHODS: The clinical protocol consists of 3D data acquisition of the craniofacial complex by cone-beam computed tomography (CBCT) and surface scanning of the plaster dental casts. The ''virtual patient'' created underwent virtual surgery and a simulation of postoperative results on hard tissues. Surgical splints were manufactured using CAD/CAM technology in order to transfer the virtual surgical plan to the operating room. Intraoperatively, both CAD/CAM and conventional surgical splints are comparable. A second set of 3D images was obtained after surgery to acquire linear measurements and compare them with measurements obtained when predicting postoperative results virtually. RESULTS: It was found a high similarity between both types of surgical splints with equal fitting on the dental arches. The linear measurements presented some discrepancies between the actual surgical outcomes and the predicted results from the 3D virtual simulation, but caution must be taken in the analysis of these results due to several variables. CONCLUSIONS: The reported case confirms the clinical feasibility of the described computer-assisted orthognathic surgical protocol. Further progress in the development of technologies for 3D image acquisition and improvements on software programs to simulate postoperative changes on soft tissue are required. PMID- 27007769 TI - Why segment the maxilla between laterals and canines? AB - INTRODUCTION: Maxillary surgery on a bone segment enables movement in the sagittal and vertical planes. When performed on multiple segments, it further provides movement in the transverse plane. Typical sites for interdental osteotomies are between laterals and canines, premolars and canines, or between incisors. Additionally, osteotomies can be bilateral, unilateral or asymmetric. The ability to control intercanine width, buccolingual angulation of incisors, and correct Bolton discrepancy are some of the advantages of maxillary segmentation between laterals and canines. OBJECTIVE: This article describes important features to be considered in making a clinical decision to segment the maxilla between laterals and canines when treating a dentoskeletal deformity. It further discusses the history of this surgical approach, the indications for its clinical use, the technique used to implement it, as well as its advantages, disadvantages, complications and stability. It is therefore hoped that this paper will contribute to disseminate information on this topic, which will inform the decision-making process of those professionals who wish to make use of this procedure in their clinical practice. CONCLUSIONS: Segmental maxillary osteotomy between laterals and canines is a versatile technique with several indications. Furthermore, it offers a host of advantages compared with single-piece osteotomy, or between canines and premolars. PMID- 27007770 TI - Tell me sweet little lies: An event-related potentials study on the processing of social lies. AB - In reading tasks, words that convey a false statement elicit an enhanced N400 brainwave response, relative to words that convey a true statement. N400 amplitude reductions are generally linked to the online expectancy of upcoming words in discourse. White lies, contrary to false statements, may not be unexpected in social scenarios. We used the event-related potential (ERP) technique to determine whether there is an impact of social context on sentence processing. We measured ERP responses to target words that either conveyed a social "white" lie or a socially impolite blunt truth, relative to semantic violations. Word expectancy was controlled for by equating the cloze probabilities of white lying and blunt true targets, as measured in previous paper-and-pencil tests. We obtained a classic semantic violation effect (a larger N400 for semantic incongruities relative to sense making statements). White lies, in contrast to false statements, did not enhance the amplitude of the N400 component. Interestingly, blunt true statements yielded both a late frontal positivity and an N400 response in those scenarios particularly biased to white lying. Thus, white lies do not interfere with online semantic processing, and they do not engage further reanalysis processes, which are typically indexed by subsequent late positivity ERP effects. Instead, an N400 and a late frontal positivity obtained in response to blunt true statements indicate that they were treated as unexpected events. In conclusion, unwritten rules of social communicative behavior influence the electrical brain response to locally coherent but socially inappropriate statements. PMID- 27007771 TI - Comparing Natural Gas Leakage Detection Technologies Using an Open-Source "Virtual Gas Field" Simulator. AB - We present a tool for modeling the performance of methane leak detection and repair programs that can be used to evaluate the effectiveness of detection technologies and proposed mitigation policies. The tool uses a two-state Markov model to simulate the evolution of methane leakage from an artificial natural gas field. Leaks are created stochastically, drawing from the current understanding of the frequency and size distributions at production facilities. Various leak detection and repair programs can be simulated to determine the rate at which each would identify and repair leaks. Integrating the methane leakage over time enables a meaningful comparison between technologies, using both economic and environmental metrics. We simulate four existing or proposed detection technologies: flame ionization detection, manual infrared camera, automated infrared drone, and distributed detectors. Comparing these four technologies, we found that over 80% of simulated leakage could be mitigated with a positive net present value, although the maximum benefit is realized by selectively targeting larger leaks. Our results show that low-cost leak detection programs can rely on high-cost technology, as long as it is applied in a way that allows for rapid detection of large leaks. Any strategy to reduce leakage should require a careful consideration of the differences between low-cost technologies and low-cost programs. PMID- 27007772 TI - Genetic characterization of the complete genome of an Aleutian mink disease virus isolated in north China. AB - The genome of a highly pathogenic strain of Aleutian disease mink virus (AMDV-BJ) isolated from a domestic farm in North China has been determined and compared with other strains. Alignment analysis of the major structural protein VP2 revealed that AMDV-BJ is unique among 17 other AMDV strains. Compared with the nonpathogenic strain ADV-G, the 3' end Y-shaped hairpin was highly conserved, while a 4-base deletion in the 5' U-shaped terminal palindrome resulted in a different unpaired "bubble" group near the NS1-binding region of the 5' end hairpin which may affect replication efficiency in vivo. We also performed a protein analysis of the NS1, NS2, and new-confirmed NS3 of AMDV-BJ with some related AMDV DNA sequence published, providing information on evolution of AMDV genes. This study shows a useful method to obtain the full-length genome of AMDV and some other parvoviruses. PMID- 27007773 TI - Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. AB - BACKGROUND: Simple immune capture assays that detect mycobacterial lipoarabinomannan (LAM) antigen in urine are promising new tools for the diagnosis of HIV-associated tuberculosis (HIV-TB). In addition, however, recent prospective cohort studies of patients with HIV-TB have demonstrated associations between LAM in the urine and increased mortality risk during TB treatment, indicating an additional utility of urinary LAM as a prognostic marker. We conducted a systematic review and meta-analysis to summarise the evidence concerning the strength of this relationship in adults with HIV-TB in sub-Saharan Africa, thereby quantifying the assay's prognostic value. METHODS: We searched MEDLINE and Embase databases using comprehensive search terms for 'HIV', 'TB', 'LAM' and 'sub-Saharan Africa'. Identified studies were reviewed and selected according to predefined criteria. RESULTS: We identified 10 studies eligible for inclusion in this systematic review, reporting on a total of 1172 HIV-TB cases. Of these, 512 patients (44 %) tested positive for urinary LAM. After a variable duration of follow-up of between 2 and 6 months, overall case fatality rates among HIV-TB cases varied between 7 % and 53 %. Pooled summary estimates generated by random-effects meta-analysis showed a two-fold increased risk of mortality for urinary LAM-positive HIV-TB cases compared to urinary LAM-negative HIV-TB cases (relative risk 2.3, 95 % confidence interval 1.6-3.1). Some heterogeneity was explained by study setting and patient population in sub-group analyses. Five studies also reported multivariable analyses of risk factors for mortality, and pooled summary estimates demonstrated over two-fold increased mortality risk (odds ratio 2.5, 95 % confidence interval 1.4-4.5) among urinary LAM-positive HIV-TB cases, even after adjustment for other risk factors for mortality, including CD4 cell count. CONCLUSIONS: We have demonstrated that detectable LAM in urine is associated with increased risk of mortality during TB treatment, and that this relationship remains after adjusting for other risk factors for mortality. This may simply be due to a positive test for urinary LAM serving as a marker of higher mycobacterial load and greater disease dissemination and severity. Alternatively, LAM antigen may directly compromise host immune responses through its known immunomodulatory effects. Detectable LAM in the urine is an independent risk factor for mortality among patients receiving treatment for HIV-TB. Further research is warranted to elucidate the underlying mechanisms and to determine whether this vulnerable patient population may benefit from adjunctive interventions. PMID- 27007774 TI - Overexpression of bromodomain factor 3 in Trypanosoma cruzi (TcBDF3) affects differentiation of the parasite and protects it against bromodomain inhibitors. AB - The bromodomain is the only protein domain known to bind acetylated lysine. In the last few years many bromodomain inhibitors have been developed in order to treat diseases such as cancer caused by aberrant acetylation of lysine residues. We have previously characterized Trypanosoma cruzi bromodomain factor 3 (TcBDF3), a bromodomain with an atypical localization that binds acetylated alpha-tubulin. In the present work we show that parasites overexpressing TcBDF3 exhibit altered differentiation patterns and are less susceptible to treatment with bromodomain inhibitors. We also demonstrate that recombinant TcBDF3 is able to bind to these inhibitors in vitro in a concentration-dependant manner. In parallel, the overexpression of a mutated version of TcBDF3 negatively affects growth of epimastigotes. Recent results, including the ones presented here, suggest that bromodomain inhibitors can be conceived as a new type of anti-parasitic drug against trypanosomiasis. PMID- 27007775 TI - Correction: How Diverse Detrital Environments Influence Nutrient Stoichiometry between Males and Females of the Co-Occurring Container Mosquitoes Aedes albopictus, Ae. aegypti, and Culex quinquefasciatus. PMID- 27007776 TI - Quantitative comparison of ligament formulation and pre-strain in finite element analysis of the human lumbar spine. AB - Data has been published that quantifies the nonlinear, anisotropic material behaviour and pre-strain behaviour of the anterior longitudinal, supraspinous (SSL), and interspinous ligaments of the human lumbar spine. Additionally, data has been published on localized material properties of the SSL. These results have been incrementally incorporated into a previously validated finite element model of the human lumbar spine. Results suggest that the effects of increased ligament model fidelity on bone strain energy were moderate and the effects on disc pressure were slight, and do not justify a change in modelling strategy for most clinical applications. There were significant effects on the ligament stresses of the ligaments that were directly modified, suggesting that these phenomena should be included in FE models where ligament stresses are the desired metric. PMID- 27007778 TI - Effect of noninvasive focused ultrasound stimulation on gamma oscillations in rat hippocampus. AB - In recent years, noninvasive focused ultrasound stimulation (FUS), with the advantage of high spatial resolution and high penetration depth, has developed rapidly for modulating neuron activities in the brain. Gamma oscillations serve to synchronize neurons and play important roles in cortical information processing and cognitive function. However, how FUS modulates gamma oscillations in the rat hippocampus is not well understood. In this work, we characterized the interactions between the gamma amplitude and phases of the delta, theta, and alpha bands during FUS. Our results show that FUS can significantly modulate the extent of phase-locked gamma amplitude and phase-amplitude coupling of brain oscillations. In summary, FUS can modulate gamma oscillations in the rat hippocampus, indicating its potential as a powerful noninvasive method to interfere with brain rhythms for diagnostic and therapeutic purposes. PMID- 27007777 TI - [Prone positioning of patients during venovenous extracorporeal membrane oxygenation is safe and feasible]. AB - BACKGROUND: Prone positioning of patients with acute respiratory distress syndrome (ARDS) has been shown to significantly improve survival rates. Prone positioning reduces collapse of dorsal lung segments with subsequent reduction of alveolar overdistension of ventral lung segments, optimizes lung recruitment and enhances drainage. Patients with ARDS treated by extracorporeal membrane oxygenation (ECMO) can also benefit from prone positioning; however, the procedure is associated with a possible higher risk of serious adverse events. OBJECTIVE: The aim of this study was to evaluate the safety and feasibility of prone positioning for patients with severe ARDS during ECMO therapy. MATERIAL AND METHODS: This study involved a retrospective analysis of all patients placed in a prone position while being treated by venovenous ECMO (vvECMO) for severe hypoxemia in ARDS as bridge to recovery in the interdisciplinary intensive care unit at the University Hospital Leipzig between January 2009 and August 2013. Baseline data, hospital mortality and serious adverse events were documented. Serious adverse events were defined as dislocation or obstruction of endotracheal tube or tracheal cannula, ECMO cannulas and cardiac arrest. Prone positioning was carried out by at least one doctor and three nurses according to a standardized protocol. Results are given as the median (1st and 3rd quartiles). RESULTS: A total of 26 patients were treated with vvECMO as bridge to recovery due to severe ARDS. Causes for ARDS were pneumonia (n = 20) and aspiration (n = 2) and four patients had different rare causes of ARDS. The median time on ECMO was 8 days (6;11) and during this period 134 turning events were documented. Patients were proned for a median of 5 (3;7) periods with a median duration of 12 h (8;12). No serious adverse events were recorded. The hospital mortality was 42% and mortality during the ECMO procedure was 35%. CONCLUSION: Prone positioning significantly reduces the mortality of patients with severe ARDS. In this series of 26 patients with severe ARDS during ECMO therapy no serious adverse events were found during the use of prone positioning. PMID- 27007780 TI - Plasma exchange and chelator therapy rescues acute liver failure in Wilson disease without liver transplantation. AB - AIM: Wilson disease (WD) in patients with a New Wilson Index (NWI) score >= 11 is fatal, and these patients are good candidates for liver transplantation (LT). However, plasma exchange and chelator therapy are indispensable and effective even for WD with a score >= 11. Moreover, continuous hemodiafiltration (CHDF) with these treatments is essential for acute liver failure (ALF) in WD with hepatic encephalopathy because CHDF can exclude toxic metabolites that may cause damage to the brain. Here, we describe four rescued patients presenting with ALF in WD and discuss the available treatment options. METHODS: We have experienced 11 male and 8 female patients presenting with WD at the Department of Pediatrics, Kumamoto University Hospital between 1999 and 2014. A male and 4 female patients were diagnosed as WD with ALF using a combination of clinical findings and biochemical tests. RESULTS: The NWI score was >= 11 in cases 1 to 3. Cases 1 and 2 with hepatic encephalopathy received plasma exchange, CHDF, coagulation factor replacement treatment (CFRT) and LT. Cases 3 and 4 without encephalopathy obtained stable status without LT by plasma exchange, blood infusion, and CFRT. CONCLUSIONS: It is better to undergo LT for WD patients with a NWI score >= 11, however, there is a possibility of remission by plasma exchange and medical therapy even without LT. WD patients with a NWI score >= 11can be rescued by conservative therapy when the ALF of WD does not present with ALF and hepatic encephalopathy. Therefore, ALF with hepatic encephalopathy itself is an indication for LT in WD. PMID- 27007779 TI - Transient Superdiffusion and Long-Range Correlations in the Motility Patterns of Trypanosomatid Flagellate Protozoa. AB - We report on a diffusive analysis of the motion of flagellate protozoa species. These parasites are the etiological agents of neglected tropical diseases: leishmaniasis caused by Leishmania amazonensis and Leishmania braziliensis, African sleeping sickness caused by Trypanosoma brucei, and Chagas disease caused by Trypanosoma cruzi. By tracking the positions of these parasites and evaluating the variance related to the radial positions, we find that their motions are characterized by a short-time transient superdiffusive behavior. Also, the probability distributions of the radial positions are self-similar and can be approximated by a stretched Gaussian distribution. We further investigate the probability distributions of the radial velocities of individual trajectories. Among several candidates, we find that the generalized gamma distribution shows a good agreement with these distributions. The velocity time series have long-range correlations, displaying a strong persistent behavior (Hurst exponents close to one). The prevalence of "universal" patterns across all analyzed species indicates that similar mechanisms may be ruling the motion of these parasites, despite their differences in morphological traits. In addition, further analysis of these patterns could become a useful tool for investigating the activity of new candidate drugs against these and others neglected tropical diseases. PMID- 27007781 TI - Identification of a Novel Point Mutation in the LEMD3 Gene in an Infant With Buschke-Ollendorff Syndrome. PMID- 27007782 TI - Embolic protection devices in percutaneous coronary intervention. AB - Clinical benefit of percutaneous coronary intervention (PCI) depends on both angiographic success at lesion site as well as the restoration of adequate macro and microvascular perfusion. The pathophysiology of embolization from coronary lesions during PCI is multifactorial, being more frequently observed in patients with acute coronary syndrome and in those with lesions at saphenous vein graft (SVG). In this population, despite successful epicardial intervention, distal tissue perfusion may still be absent in up to a quarter of all PCI. Multiple devices and pharmacologic regimens have been developed and refined in an attempt to protect the microvascular circulation during PCI. Among them, embolic protection devices have raised as an attractive adjunctive toll due to their ability to retain debris and potentially prevent distal embolization, reducing major adverse cardiac events. Currently, their use has been validated for the treatment of SVG lesions but failed to show effectiveness in the percutaneous approach of acute coronary syndrome patients, including those with ST elevation myocardial infarction. PMID- 27007783 TI - Evaluation of thermal regimes for transported ambassador ectotherms: One size does not fit all. AB - Providing appropriate environmental temperatures for captive ectotherms should be a husbandry priority. This can be especially challenging for ectotherms that are routinely transported, such as those used in education programs at zoos, because they are unable to thermoregulate while confined in non-temperature controlled, compact carriers. To assess if ectotherms used in the Fort Wayne Children's Zoo's outreach programs experienced appropriate transit temperatures during cold weather, we placed temperature loggers inside two sizes of transport carriers, half containing a heat source (bottle of hot water) and half not (control). While transport temperatures were appropriate for many ectotherms, this simple procedure failed to meet the thermal preferences of species with relatively low or high preferred temperatures such as the eastern tiger salamander (Ambystoma tigrinum) and the spiny-tailed lizard (Uromastyx maliensis), respectively. We found large heated carriers were warmer than small heated carriers, but the temperatures of control carriers did not differ. Despite considerable interspecific variation, large heated carriers provided higher thermal quality environments than both small heated and control carriers for all species except eastern tiger salamanders. We suggest further thermal monitoring of ectotherms during transit with the aim of identifying appropriate heat sources and developing efficient and effective transportation protocols. This could be achieved by modifying transport carriers so that animals are able to thermoregulate. Limiting or ceasing their use when appropriate temperatures cannot be provided may be necessary. Particular attention should be given to species with temperature preferences markedly different than the majority of others in a given collection. Zoo Biol. 35:339-345, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27007784 TI - Urological Complications and BK Virus-Associated Diseases Under Allogenic Stem Cell Transplantation. AB - : Every year 50,000 patients receive a stem cell transplantation worldwide, but there is lack of data pertaining to urological complications. METHODS: We performed a retrospective analysis of all adult patients undergoing their first allogenic stem cell transplantation from January 2011 to June 2013 in our institution. Statistical tests performed were Pearson's correlation, chi-square testing and logistic regression using SPSS 22.0. RESULTS: We identified 39 patients (22 males, 17 females). Twenty four patients (61.5%) had a urological complication. Most frequent urologic complications were bacterial urinary tract infection (n = 13; 33.3%), acute renal failure (n = 6; 15.4%) and BK virus associated haemorrhagic cystitis (n = 5; 12.8%). BK viruria was detected in 12 patients (30.8%). We observed an association of creatinine increase (about 20 umol/l at time of onset of BK viruria) with BK viruria (Pearson's correlation 0.64; p = 0.01), and BK viruria is significantly linked to acute renal failure (Pearson's correlation 0.35; p = 0.029). In univariate regression, BK viruria is significantly linked to urological complication (p = 0.025). CONCLUSIONS: We suggest that BK virus infection during stem cell transplantation can lead to BK virus associated nephropathy, which is so far only known from patients after kidney transplantation. PMID- 27007785 TI - Assessment of the C1 Lateral Mass Screw Trajectory and Position Using Plain Radiographs: A Comparison With Computed Tomography. AB - STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to provide methods for predicting ideal trajectory and position of C1 lateral mass screw (C1LMS) from plain radiographs. SUMMARY OF BACKGROUND DATA: There has been no study on prediction of C1LMS position using plain radiographs. METHODS: A total of 40 consecutive subjects (with 79 screws) who had undergone C1LMS placement were enrolled. To evaluate the C1LMS position, the positions of screw head and tips on anteroposterior radiographs, screw length, and height on lateral radiograph were graded as 0, I, and II, respectively. On the postoperative computed tomography images, we analyzed lateral mass (LM) perforation, screw thread engagement percent (%), bicortical fixation, extruded screw length, and violation of adjacent joints. RESULTS: Screws with tip located medial to LM (tip 0) showed LM perforation in all cases. Polyaxial head located within the LM (head 0) or crossing the lateral margin of the LM (head I) showed no LM perforation. Screw-thread engagement percent was the highest with head I-tip I (medial half of LM) position (97.6%), followed by head 0-tip I (90.5%) and head I-tip II (lateral half of LM) (86.4%). Screws longer than the posterior half of C1 anterior arch (AA) showed bicortical fixation in all cases with mean extruded screw length of 1.9 mm. Adjacent joint was not violated in 98%, with the screw height below half of C1AA. CONCLUSIONS: On an anteroposterior radiograph, a C1LMS with the screw head located on the lateral margin of the LM and with the screw tip in the medial half of the LM resulted in the safest and longest trajectory. On lateral radiograph, a screw tip that is placed within the anterior-inferior quadrant of the C1AA results in safe bicortical fixation without injury to the adjacent structures. These plain radiographic findings may be helpful both postoperatively and intraoperatively for assessing the trajectory and length of the screw. PMID- 27007786 TI - Modified Pedicle Subtraction Osteotomy as a Salvage Method for Failed Short Segment Pedicle Instrumentation in the Treatment of Thoracolumbar Fracture. AB - STUDY DESIGN: Retrospective study. SUMMARY OF BACKGROUND DATA: Short-segment pedicle instrumentation (SSPI) is widely used to treat thoracolumbar junction fracture. Implant failure is the most common complication of SSPI and often necessitates revision surgery. The stand-alone anterior technique for failed SSPI provides excellent decompression and anterior column reconstruction, but it is incapable of restoring normal stability. High rate of complications is solely attributable to the anterior approach. Thus, the reconstruction of the anterior column with posterior compression instrumentation is the strategy of choice. In this study, we use a modified pedicle subtraction osteotomy (PSO) technique through a single posterior approach as the salvage method for the failed SSPI. MATERIALS AND METHODS: Thirteen patients with failed SSPI after thoracolumbar fracture were included and followed up at regular intervals. Revision indications include intractable pain, deteriorating neurological deficits, and progressive deformity. The modified PSO was performed. After osteotomy, the anterior cortex was thinned and the anterior longitudinal ligament was also preserved to maintain stability during correction. Autograft was inserted into the osteotomy gap to increase stability and fusion rate. The correction had been achieved with closure. We evaluated the patients' clinical symptoms, segmental kyphosis correction, bony fusion time, and complications. RESULTS: Segmental kyphosis correction was from preoperative average 20.9 degrees (range, 9.5-38.5 degrees) to 3.0 degrees (range, 1-5.5 degrees) immediately after operation and 6.1 degrees (range, 3-8 degrees at the last follow-up). Bony fusion was confirmed on radiographs in all patients at an average of 9.9 months (range, 7.5-12 mo) after revision surgery. There was no implant failure in any of the 13 patients. Average preoperative visual analog scale was 6.5 (range, 5-9) and reduced to 3.7 (range, 2-5) at the last follow-up. There was also a significant decrease in mean preoperative Oswestry Disability Index from 55.2 (range, 38-76) to 32.8 (range, 16-56). No patients suffered any neurological deterioration related to revision surgery. Complications were encountered in 6 patients (46.1%), including 4 with cerebrospinal fluid leak and 2 with superficial wound infection. All these complications were managed conservatively and none of them underwent reoperation. CONCLUSION: We conclude that modified PSO possesses the advantages of excellent kyphosis correction, a safe and reliable salvage alternative for the revision of SSPI failure. PMID- 27007787 TI - Effect of rAAV2-hTGFbeta1 Gene Transfer on Matrix Synthesis in an In Vivo Rabbit Disk Degeneration Model. AB - STUDY DESIGN: In vivo gene transfer for disk regeneration. OBJECTIVE: To evaluate the efficiency and effect of human transforming growth factor beta1 (hTGFbeta1) gene transfer mediated by adeno-associated virus (AAV) in a rabbit disk degeneration model induced by fibronectin fragment (Fn-f). SUMMARY OF BACKGROUND DATA: Gene therapy for disk degeneration has been reported to be effective. Nevertheless, few investigations have targeted the degenerative nucleus pulposus (NP) cells in vivo. Fn-f-induced degeneration has been previously verified to be a useful model for the study of disk degeneration at the molecular level. AAV vector is well suited for gene transfer in the disk for its lower immunogenicity and higher safety. MATERIALS AND METHODS: The early dedifferentiated NP cells were transfected with rAAV2-mediated enhanced green fluorescent protein (EGFP) gene in vitro. Fluorescence expression was observed 48 hours later. The rabbit disk degeneration model was established with a microinjection of Fn-f. Ninety-six degenerative disks of 24 rabbits were injected with rAAV2-hTGFbeta1 (group A), rAAV2-EGFP (group B), or PBS (group C). Immunohistochemical staining for hTGFbeta1 and fluorescence observation were performed at the 1- and 12-week time points, respectively. 35S-sulfate incorporation assay and Western blot analysis were used to measure the synthesis of proteoglycan and collagen type II at 4-, 8 , and 12-week time points. RESULTS: The dedifferentiated NP cells exhibited intensive fluorescence expression in vitro, with a transfection rate of 90%. In vivo, disks in group A showed enhanced positive hTGFbeta1 immunostaining at the 1 week time point. At the 4-, 8-, and 12-week time points, disks in group A exhibited significantly increased proteoglycan and collagen type II synthesis compared with the other 2 groups (P<0.01). Abundant green fluorescence was observed in the disks in group B at the 12-week time point. CONCLUSIONS: Early degenerative NP cells are susceptible to AAV-mediated gene transfer in vitro and in vivo. The rapid and prolonged target protein expressions and increased matrix synthesis indicated that AAV-mediated therapeutic gene transfer can be a promising form of treatment for disk regeneration in vivo. PMID- 27007788 TI - Accuracy of Pedicle Screw Placement in Children 10 Years or Younger Using Navigation and Intraoperative CT. AB - STUDY DESIGN: A consecutive case series. OBJECTIVE: To determine the revision rate for pedicle screws placed using intraoperative CT and image-guided navigation in children 10 years or younger. SUMMARY OF BACKGROUND DATA: Screws are frequently used for spinal instrumentation in young children, although this is only by physician-directed use. This is a multicenter retrospective study of patients aged 10 years or younger, who underwent spinal screw instrumentation with image-guided navigation. We hypothesized that intraoperative navigation would result in a high rate of accuracy for screw placement. METHODS: Between 2007 and 2013, 130 pedicle and 7 lateral mass screws were placed in 16 consecutive patients undergoing a total of 17 surgeries at 2 institutions. Mean age at surgery was 6.9 years (range, 0.8-10.9 y). Screws were placed using an open technique with intraoperative CT (O-arm) and image-guided navigation (Stealth). Procedures included: growing spine device (3), hemivertebrae excision (4), posterior fusion (7), cervical fusion (2), and vertebral column resection (1). Congenital deformity was the most common diagnosis. Primary outcome measures were need for intraoperative screw revision or complication associated with screw placement. RESULTS: Mean number of screws used per procedure was 8.1 (range, 2 17). Screws were placed from C1 to L5. Of the 137 screws, 3 required revision to shorter screws for an overall accuracy rate of 97.8%. In 1 case, a right T3 screw was revised due to anterior penetration. In another case, left-sided T1 and T2 pedicle screws were shortened 5 mm because they had penetrated the anterior aspect of their respective vertebral bodies. There were no screw-related complications. CONCLUSIONS: In this series, image-guided navigation resulted in accurate placement of screws in patients aged 10 years or younger with no associated intraoperative complications. The navigated accuracy rate (97.8%) is significantly higher (P=0.01) than the reported 90.9% pedicle screw accuracy rate without navigation in the same age group by Baghdadi and colleagues. Intraoperative CT and image guidance were useful in our practice for placement of screws in skeletally immature patients. PMID- 27007789 TI - In Vivo Reconstruction of Lumbar Erector Spinae Architecture Using Diffusion Tensor MRI. AB - STUDY DESIGN: Diffusion tensor magnetic resonance imaging (DT-MRI) reconstruction of lumbar erector spinae (ES) compared with cadaver dissection. OBJECTIVE: The aim of this study was to reconstruct the human lumbar ES from in vivo DT-MRI measurements and to compare the results with literature and cadaver dissection. SUMMARY OF BACKGROUND DATA: DT-MRI enables 3-dimensional in vivo reconstruction of muscle architecture. Insight in ES architecture may improve the understanding of low back function. Furthermore, DT-MRI reconstructions allow individualized biomechanical modeling, which may serve as a clinical tool in injury evaluation and in improvement of understanding of pathologies like scoliosis. MATERIALS AND METHODS: The lumbar spine of 1 healthy male volunteer was scanned using a 3.0 T clinical MRI scanner. MRI data acquisition consisted of 3 parts: (1) high resolution T1-weighted turbo spin echo for anatomical reference; (2) DT-MRI measurements for fiber tractography; (3) dual echo gradient echo sequence for signal correction purposes. After processing, DT-MRI data were exported to a custom-built software program for fiber tractography. The resulting reconstructions were anatomically validated by comparison with cadaver dissection and literature. RESULTS: DT-MRI reconstruction of 4 parts of the lumbar ES (thoracic part of iliocostalis lumborum, lumbar part of iliocostalis lumborum, thoracic part of longissimus thoracis, and lumbar part of longissimus thoracis) adequately reflected its complex geometry. Some inaccuracies were found in reconstruction details. DT-MRI reconstructions were generally in agreement with anatomical descriptions from literature and with findings in a dissected cadaver specimen. CONCLUSIONS: DT-MRI enables anatomically valid reconstruction of ES architecture. However, for reliable reconstruction of the smallest fascicles and attachments a higher resolution or application of higher-order models is needed. Reconstructions can be used as input for estimation of muscle architecture parameters in individualized biomechanical modeling. Such models are promising as a tool in clinical evaluation and in research of low back pain mechanisms. PMID- 27007790 TI - A Genetic Test Predicts Providence Brace Success for Adolescent Idiopathic Scoliosis When Failure Is Defined as Progression to >45 Degrees. AB - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To determine whether a genetic test is associated with successful Providence bracing for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Genetic factors have been defined that predict the risk of progression of AIS in a polygenic fashion. From these data, a commercially available genetic test, ScoliScore, was developed. It is now used in clinical practice for counseling and to guide clinical management. Bracing is a mainstay of treatment for AIS. Large efforts have been made recently to reduce potential confounding across studies of different braces; however, none of these have considered genetics as a potential confounder. In particular, ScoliScore has not been evaluated in a population undergoing bracing. METHODS: We conducted a retrospective cohort study in which we identified a population of AIS patients who were initiated with Providence bracing and followed over time. Although these patients did not necessarily fit the commercial indications for ScoliScore, we contacted the patients and obtained a saliva sample from each for genetic analysis. We then tested whether ScoliScore correlated with the outcome of their bracing therapy. RESULTS: We were able to contact and invite 25 eligible subjects, of whom 16 (64.0%) returned samples for laboratory analysis. Patients were followed for an average of 2.3 years (range, 1.1-4 y) after initiation of the Providence brace. Eight patients (50.0%) progressed to >45 degrees, whereas the other 8 patients (50.0%) did not. The mean ScoliScore among those who progressed to >45 degrees was higher than that among those who did not (176 vs. 112, P=0.030). CONCLUSIONS: We demonstrate that a genetic test correlates with bracing outcome. It may be appropriate for future bracing studies to include analysis of genetic predisposition to limit potential confounding. PMID- 27007791 TI - Postoperative Complications Within the First Year After Extreme Lateral Interbody Fusion: Experience of the First 108 Patients. AB - STUDY DESIGN: Retrospective chart review. OBJECTIVE: To determine complications within the first year after undergoing extreme lateral interbody fusion (XLIF). SUMMARY OF BACKGROUND DATA: There are a growing but limited number of reports in the literature regarding early postoperative complications after XLIF. METHODS: We performed a retrospective chart review of perioperative complications of a case series of the first 108 patients to undergo XLIF at our institution between 2007 and 2009. We also recorded estimated blood loss, surgical time, and hospital length of stay for each procedure. RESULTS: There were 25 complications (23%) overall in patients who underwent the XLIF procedure. Four patients (3.7%) experienced major complications including: vertebral body fracture, contralateral nerve root injury, dense quadriceps paresis, and persistent stenosis. Three of these patients underwent revision surgery. There were 21 minor (19.4%) complications the vast majority of which consisted of approach-related thigh pain and/or paresthesias that all ultimately resolved. CONCLUSIONS: Transient ipsilateral thigh numbness, pain, and/or hip flexor weakness is a frequent postoperative finding most commonly when the L4-L5 level is instrumented. Dense femoral nerve palsy is a debilitating complication that may occur despite intraoperative neurophysiological monitoring. It should be noted that this retrospective study may underreport the true incidence of complications among these patients. PMID- 27007792 TI - Vertebral Derotation by Vertebral Column Manipulator Improves Postoperative Radiographs Outcomes of Lenke 5C Patients for Follow-up of Minimum 2 Years. AB - STUDY DESIGN: This was a retrospective study. OBJECTIVE: The aim of this study was to compare radiographic outcomes of Lenke 5C adolescent idiopathic scoliosis (AIS) patients treated by vertebral column manipulator (VCM) or simple rod derotation (SRD) maneuver. SUMMARY OF BACKGROUND DATA: The direct vertebral rotation (DVR) technique has demonstrated better rotational and coronal correction than SRD, but clinical radiographic outcomes for Lenke 5C AIS following DVR using a VCM derotational device have not been described. MATERIALS AND METHODS: A retrospective study was carried out in 39 Lenke 5C AIS patients treated by VCM (n=20) or SRD (n=19) techniques between April 2008 and June 2011. All patients had complete clinical record and radiographic data. Nine radiographic variables were collected and compared at 3 time points (preoperative, immediate postoperative, and minimum 2-year follow-up) between both groups. RESULTS: Scoliosis was successfully corrected in both groups. All patients obtained good coronal and sagittal balance, and no severe complications occurred. The postoperative apical rotation corrective rate of the VCM and SRD groups were 55.1% and 25.5%, respectively (P < 0.05). Lowest instrumented vertebra and stable vertebra (LIV-SV) was statistically significant between the VCM and SRD groups, the mean values were 1.2 +/- 0.4 level and 0.7 +/- 0.5 level (P < 0.05). The main curve corrective rates and LIV-tilt angle correction rates were not significantly different between groups, but it showed a spontaneous correction for the coronal LIV-tilt angle for both groups at the last follow-up. CONCLUSIONS: VCM improved postoperative apical axial rotational correction and lessened the lumbar fusion segment compared with the SRD technique, which might have a potential trend to reserve lumbar mobility. PMID- 27007793 TI - Effect of low-dose spironolactone on resistant hypertension in type 2 diabetes mellitus: a randomized controlled trial in a sub-Saharan African population. AB - BACKGROUND: Low-dose spironolactone has been proven to be effective for resistant hypertension in the general population, but this has yet to be confirmed in type 2 diabetic (T2DM) patients. We assessed the efficacy of a low-dose spironolactone on resistant hypertension in a sub-Saharan African population of T2DM patients from Cameroon. METHODS: This was a four-week single blinded randomized controlled trial in 17 subjects presenting with resistant hypertension in specialized diabetes care units in Cameroon. They were randomly assigned to treatment with a daily 25 mg of spironolactone (n = 9) or to an alternative antihypertensive regimen (n = 8), on top of any ongoing regimen and prevailing lifestyle prescriptions. They were seen at the start of the treatment, then 2 and 4 weeks later. The primary outcome was change in office and self-measured blood pressure (BP) during follow-up, and secondary outcomes were changes in serum potassium, sodium, and creatinine levels. RESULTS: Compared with alternative treatment, low dose spironolactone was associated with significant decrease in office systolic BP (-33 vs. -14 mmHg; p = 0.024), and in diastolic BP (-14 vs. -5 mmHg; p = 0.006). After 1 month of spironolactone, all the patients were controlled based on BP below 130/80 mmHg, with significant office BP reduction from 158 +/- 17/86 +/- 11 to 125 +/- 11/72 +/- 8, vs. 158 +/- 8/94 +/- 8 to 144 +/- 17/89 +/- 12 mmHg in the alternative treatment group. There was no significant variation in sodium and creatinine levels in both groups, but a mild increase of potassium levels in the spironolactone group. INTERPRETATION: Add-on low-dose spironolactone was effective in reducing BP to optimal levels in T2DM Cameroonian patients despite mild increase in serum potassium. Trial registration ClinicalTrials.gov Identifier NCT02426099. Date of registration April 2015. PMID- 27007794 TI - Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population. AB - PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided. RESULTS: Forty different lines were identified. The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population. CONCLUSIONS: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines. PMID- 27007795 TI - Perceptions of Institutional Betrayal Predict Suicidal Self-Directed Violence Among Veterans Exposed to Military Sexual Trauma. AB - OBJECTIVES: We examined perceptions of institutional betrayal among Veterans exposed to military sexual trauma (MST) and whether perceptions of institutional betrayal are associated with symptoms of posttraumatic stress disorder (PTSD), depression, and suicidal ideation and attempt after MST. METHOD: A total of 49 Veterans with MST completed self-report measures and interviews in a Veterans Health Administration setting. RESULTS: Many participants reported perceptions that a military institution created an environment in which MST seemed common, likely to occur, and did not proactively prevent such experiences. Many participants expressed difficulty reporting MST and indicated that the institutional response to reporting was inadequate. Over two-thirds perceived that the institution had created an environment in which they no longer felt valued or in which continued membership was difficult. Perceptions of institutional betrayal were associated with PTSD symptoms, depressive symptoms, and increased odds of attempting suicide after MST. In contrast, perceptions of institutional betrayal were not associated with post-MST suicidal ideation. Among the subsample of Veterans exposed to military sexual assault, the association between institutional betrayal and PTSD symptoms approached significance. CONCLUSIONS: Perceptions regarding institutional betrayal appear to be highly relevant to MST and its sequelae. These findings underscore the importance of Veterans' perceptions of the military institution's efforts to prevent and respond to MST to individual recovery from sexual trauma. Additional research regarding the association between institutional betrayal and health-related outcomes is needed. PMID- 27007796 TI - HAMP Gene Mutation Associated with Juvenile Hemochromatosis in Brazilian Patients. PMID- 27007797 TI - Meat intake among adults: a population-based study in the city of Campinas, Brazil. A cross-sectional study. AB - CONTEXT AND OBJECTIVE: Meat is a food with high nutritional density that has significant participation in the Brazilian diet. However, in excess it can cause harm to health. The aim of this study was to analyze the meat intake (g/day) among adults according to sociodemographic, behavioral and health situation characteristics, and to assess the types of meat most consumed. DESIGN AND SETTING: Cross-sectional population-based study conducted in the city of Campinas, Sao Paulo, Brazil, in 2008 and 2009. METHODS: Two-stage cluster sampling was used. The analysis included 948 adults between 20 and 59 years, who were participants in the Campinas Health Survey. Meat intake was assessed using 24-hour dietary recall. RESULTS: The mean meat intake adjusted for sex and age was 182.3 g (95% CI: 170.6-193.9 g), with significantly lower intake among women, individuals aged 50 years or over, those with the presence of two or more self reported chronic diseases and those with three or more health complaints. Higher meat intake was found in segments with intermediate monthly family income (between 1 and 3 minimum wages), those with 16 or more appliances per household and those who consumed soft drinks seven days a week. Beef was consumed most frequently (44%) among the meats in the diet, followed by poultry, fish and pork. CONCLUSION: The data from this study reveal high meat intake in the population of Campinas and identify the segments that need to be prioritized for strategies directed towards appropriate meat intake. PMID- 27007798 TI - The 5As of healthy pregnancy weight gain: possible applications in the Brazilian context to improve maternal-fetal health. PMID- 27007799 TI - Alcohol consumption during pregnancy and perinatal results: a cohort study. AB - CONTEXT AND OBJECTIVE: Alcohol consumption during pregnancy is a significant social problem that may be associated with adverse perinatal outcomes. The aim of this study was to describe alcohol consumption during pregnancy and to study its association with low birth weight, newborns small for gestational age and preterm birth. DESIGN AND SETTING: Nested cohort study, in the city of Ribeirao Preto, Sao Paulo, Brazil. METHODS: 1,370 women and their newborns were evaluated. A standardized questionnaire on health and lifestyle habits was applied to the mothers. Anthropometry was performed on the newborns. Alcohol consumption was defined as low, moderate or high, as defined by the World Health Organization. Adjusted logistic regression analysis was used. RESULTS: 23% of the women consumed alcohol during pregnancy. Consumption mainly occurred in the first trimester (14.8%) and decreased as the pregnancy progressed. The median alcohol intake was 3.89 g (interquartile range, IQR = 8 g) per day. In the unadjusted analysis, alcohol consumption increased the risk of low birth weight almost twofold (odds ratio, OR 1.91; 95% confidence interval, CI: 1.25-2.92). The risk was lower in the adjusted analysis (OR 1.62; 95% CI: 1.03-2.54). Alcohol consumption did not show associations with small for gestational age or preterm birth. There was greater risk of low birth weight and newborns small for gestational age and preterm birth among mothers who were both smokers and drinkers. CONCLUSIONS: The alcohol consumption rate during pregnancy was 23% and was independently associated with low birth weight, but there was no risk of newborns small for gestational age or preterm birth. PMID- 27007800 TI - Effect of preoperative gabapentin on pain intensity and development of chronic pain after carpal tunnel syndrome surgical treatment in women: randomized, double blind, placebo-controlled study. AB - CONTEXT AND OBJECTIVES: Effective postoperative analgesia is important for reducing the incidence of chronic pain. This study evaluated the effect of preoperative gabapentin on postoperative analgesia and the incidence of chronic pain among patients undergoing carpal tunnel syndrome surgical treatment. DESIGN AND SETTINGS: Randomized, double-blind controlled trial, Federal University of Sao Paulo Pain Clinic. METHODS: Forty patients aged 18 years or over were randomized into two groups: Gabapentin Group received 600 mg of gabapentin preoperatively, one hour prior to surgery, and Control Group received placebo. All the patients received intravenous regional anesthesia comprising 1% lidocaine. Midazolam was used for sedation if needed. Paracetamol was administered for postoperative analgesia as needed. Codeine was used additionally if the paracetamol was insufficient. The following were evaluated: postoperative pain intensity (over a six-month period), incidence of postoperative neuropathic pain (over a six-month period), need for intraoperative sedation, and use of postoperative paracetamol and codeine. The presence of neuropathic pain was established using the DN4 (Douleur Neuropathique 4) questionnaire. Complex regional pain syndrome was diagnosed using the Budapest questionnaire. RESULTS: No differences in the need for sedation, control over postoperative pain or incidence of chronic pain syndromes (neuropathic or complex regional pain syndrome) were observed. No differences in postoperative paracetamol and codeine consumption were observed. CONCLUSIONS: Preoperative gabapentin (600 mg) did not improve postoperative pain control, and did not reduce the incidence of chronic pain among patients undergoing carpal tunnel syndrome surgery. PMID- 27007801 TI - The Prognostic Role of Serum Uric Acid (SUA) in Coronary Artery Disease: PerSUAsive Data Plea for a Large Morbidity-Mortality Trial. PMID- 27007802 TI - New small-intestine modeling method for surface-based computational human phantoms. AB - When converting voxel phantoms to a surface format, the small intestine (SI), which is usually not accurately represented in a voxel phantom due to its complex and irregular shape on one hand and the limited voxel resolutions on the other, cannot be directly converted to a high-quality surface model. Currently, stylized pipe models are used instead, but they are strongly influenced by developer's subjectivity, resulting in unacceptable geometric and dosimetric inconsistencies. In this paper, we propose a new method for the construction of SI models based on the Monte Carlo approach. In the present study, the proposed method was tested by constructing the SI model for the polygon-mesh version of the ICRP reference male phantom currently under development. We believe that the new SI model is anatomically more realistic than the stylized SI models. Furthermore, our simulation results show that the new SI model, for both external and internal photon exposures, leads to dose values that are more similar to those of the original ICRP male voxel phantom than does the previously constructed stylized SI model. PMID- 27007803 TI - Quantitative Sodium MR Imaging at 7 T: Initial Results and Comparison with Diffusion-weighted Imaging in Patients with Breast Tumors. AB - Purpose To investigate the clinical feasibility of a quantitative sodium 23 ((23)Na) magnetic resonance (MR) imaging protocol developed for breast tumor assessment and to compare it with 7-T diffusion-weighted imaging (DWI). Materials and Methods Written informed consent in this institutional review board-approved study was obtained from eight healthy volunteers and 17 patients with 20 breast tumors (five benign, 15 malignant). To achieve the best image quality and reproducibility, the (23)Na sequence was optimized and tested on phantoms and healthy volunteers. For in vivo quantification of absolute tissue sodium concentration (TSC), an external phantom was used. Static magnetic field, or B0, and combined transmit and receive radiofrequency field, or B1, maps were acquired, and image quality, measurement reproducibility, and accuracy testing were performed. Bilateral (23)Na and DWI sequences were performed before contrast material-enhanced MR imaging in patients with breast tumors. TSC and apparent diffusion coefficient (ADC) were calculated and correlated for healthy glandular tissue and benign and malignant lesions. Results The (23)Na MR imaging protocol is feasible, with 1.5-mm in-plane resolution and 16-minute imaging time. Good image quality was achieved, with high reproducibility (mean TSC values +/- standard deviation for the test, 36 mmol per kilogram of wet weight +/- 2 [range, 34-37 mmol/kg]; for the retest, 37 mmol/kg +/- 1 [range, 35-39 mmol/kg]; P = .610) and accuracy (r = 0.998, P < .001). TSC values in normal glandular and adipose breast tissue were 35 mmol/kg +/- 3 and 18 mmol/kg +/- 3, respectively. In malignant lesions (mean size, 31 mm +/- 24; range, 6-92 mm), the TSC of 69 mmol/kg +/- 10 was, on average, 49% higher than that in benign lesions (mean size, 14 mm +/- 12; range, 6-35 mm), with a TSC of 47 mmol/kg +/- 8 (P = .002). There were similar ADC differences between benign ([1.78 +/- 0.23] * 10(-3) mm(2)/sec) and malignant ([1.03 +/- 0.23] * 10(-3) mm(2)/sec) tumors (P = .002). ADC and TSC were inversely correlated (r = -0.881, P < .001). Conclusion Quantitative (23)Na MR imaging is clinically feasible, may provide good differentiation between malignant and benign breast lesions, and demonstrates an inverse correlation with ADC. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 27007804 TI - Various Acylglycerols from Common Oils Exert Different Antitumor Activities on Colorectal Cancer Cells. AB - Colorectal cancer is one of the leading causes of death in Western countries; therefore, the implementation of healthy dietary habits in order to prevent its occurrence is a desirable action. We show here that both free fatty acids (FFAs) and some acylglycerols induce antitumoral actions in the colorectal cancer cell line HT-29. We tested several C18 polyunsaturated fatty acid-enriched oils (e.g., sunflower and Echium) as well as other oils, such as arachidonic acid-enriched (Arasco(r)) and docosahexaenoic acid-enriched (Marinol(r) and cod liver oil), in addition to coconut and olive oils. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide test indicated inhibitory effects on HT-29 cells viability for FFAs, and monoacylglycerol and diacylglycerol (DAG) species, while the lactate dehydrogenase test proved that FFAs were the more effective species to induce membrane injury. Conversely, all species did not exhibit actions on CCD 18 normal human colon cells viability. Furthermore, transmission electron microscopy showed the presence of necrosis and apoptosis, while the monoacylglycerol lipase (MAGL) inhibition test demonstrated high activity for 2 monoacylglycerols derived from Arasco and sunflower oils. However, different monoacylglycerols and DAGs have also the potential for MAGL inhibition. Therefore, checking for activity on colon cancer cells of specifically designed acylglycerol-derivative species would be a suitable way to design functional foods destined to avoid colorectal cancer initiation. PMID- 27007805 TI - Analysis of Factors Influencing Inpatient and Outpatient Satisfaction with the Chinese Military Health Service. AB - BACKGROUND: Relatively few articles have focused on exploring factors influencing soldiers' overall satisfaction and differences between inpatients' and outpatients' satisfaction, particularly in the Chinese army. Elucidating factors influencing military inpatient and outpatient care separately and analyzing their differences may provide more information for the health system. METHODS: The Revised China National Health Service Survey questionnaire was used in the survey. The questionnaire included 5 sections and 32 items concerning demographic, inpatient, and outpatient characteristics and perception variables for both inpatients and outpatients. Bivariate and multivariate techniques were used to reveal relationships between satisfaction and the variables assessed. RESULTS: Outpatients' and inpatients' overall satisfaction rates were 19.0% and 18.5%, respectively. The strongest determinant of outpatients' satisfaction was satisfaction with doctor's communication regarding therapeutic regimen followed by length of military service, level of trust in medical staff, and disease severity. Determinants of inpatients' satisfaction included staff categories, satisfaction with environment, and satisfaction with medical quality. CONCLUSION: The factors influencing military outpatients' satisfaction differed from those of inpatients. Exploring the causes of satisfaction and dissatisfaction with military health institutions is important in their fulfillment of their responsibility to maintain soldiers' health. PMID- 27007806 TI - Black Currant (Ribes nigrum L.) Extract Induces Apoptosis of MKN-45 and TE-1 Cells Through MAPK- and PI3K/Akt-Mediated Mitochondrial Pathways. AB - Black currant extract (BCE) is rich in polyphenols and can induce apoptosis in various cancer cells, but the molecular mechanism by which BCE induces cancer cell apoptosis has not been reported. The aim of this work was to elucidate the antitumor effect of BCE and the signal transduction pathways involved. MTT test results revealed that the viability of MKN-45 and TE-1 cells treated with BCE gradually decreased in a concentration-dependent manner, with significant effects achieved after 12 h of treatment. MKN-45 and TE-1 cells clearly showed characteristics of apoptosis: shrinkage, cytoplasmic condensation, and formation of cytoplasmic filaments, even partial detachment. In addition, these results showed MKN-45 cells showed a higher level of apoptosis than TE-1 cells when treated with BCE. Western blot assays showed that the Bcl-2/Bax ratio decreased in both MKN-45 and TE-1 cells, indicating that BCE induced apoptosis through the mitochondrial pathway. In addition, BCE-induced apoptosis was mediated by mitochondrial dysfunction involving the PI3K/Akt pathway in both MKN-45 and TE-1 cells. However, BCE-induced cell apoptosis was mediated by the Fas receptor pathway in MKN-45 cells but not in TE-1 cells. BCE-induced apoptosis in MKN-45 cells was associated with the MAP-kinase signaling pathway through the activation of p38 and JNK and the inactivation of Erk1/2. However, it was associated with the MAP-kinase signaling pathway only by means of activation of p38 and JNK in TE 1 cells. These results showed that BCE induces apoptosis of MKN-45 and TE-1 cells through MAPK- and PI3K/Akt-mediated mitochondrial pathways. Thus, BCE may be a promising anticancer candidate. PMID- 27007807 TI - BiVO4 {010} and {110} Relative Exposure Extent: Governing Factor of Surface Charge Population and Photocatalytic Activity. AB - The {010} and {110} crystal facets of monoclinic bismuth vanadate (m-BiVO4) has been demonstrated to be the active reduction and oxidation sites, respectively. Here, we show using dual-faceted m-BiVO4 with distinctly different dominant exposed facets, one which is {010}-dominant and the other {110}-dominant, contrary to prediction, the former m-BiVO4 exhibits superior photooxidation activities. The population of photogenerated electrons and holes on the surface are revealed to be proportional to the respective surface areas of {010} and {110} exposed on m-BiVO4, as evidenced by steady-state photoluminescence (PL) measurements in the presence of charge scavengers. The better photoactivity of {010}-dominant m-BiVO4 is attributed to prompt electron transfer facilitated by the presence of more photogenerated electrons on the larger {010} surface. Additionally, the greater extent of electron trapping in {110}-dominant m-BiVO4 also deteriorates its photoactivity by inducing electron-hole pair recombination. PMID- 27007808 TI - Infectious Disease and Grouping Patterns in Mule Deer. AB - Infectious disease dynamics are determined, to a great extent, by the social structure of the host. We evaluated sociality, or the tendency to form groups, in Rocky Mountain mule deer (Odocoileus hemionus hemionus) from a chronic wasting disease (CWD) endemic area in Saskatchewan, Canada, to better understand factors that may affect disease transmission. Using group size data collected on 365 radio-collared mule deer (2008-2013), we built a generalized linear mixed model (GLMM) to evaluate whether factors such as CWD status, season, habitat and time of day, predicted group occurrence. Then, we built another GLMM to determine factors associated with group size. Finally, we used 3 measures of group size (typical, mean and median group sizes) to quantify levels of sociality. We found that mule deer showing clinical signs of CWD were less likely to be reported in groups than clinically healthy deer after accounting for time of day, habitat, and month of observation. Mule deer groups were much more likely to occur in February and March than in July. Mixed-sex groups in early gestation were larger than any other group type in any season. Groups were largest and most likely to occur at dawn and dusk, and in open habitats, such as cropland. We discuss the implication of these results with respect to sociobiology and CWD transmission dynamics. PMID- 27007809 TI - Role of Assay Type in Determining Free 25-Hydroxyvitamin D Levels in Diverse Populations. PMID- 27007810 TI - Investigating metacognition, cognition, and behavioral deficits of college students with acute traumatic brain injuries. AB - OBJECTIVE: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. PARTICIPANTS: Participants were 121 college students who endorsed a mild TBI, and 121 college students with no history of a TBI were matched on sex and ethnicity to examine potential differences between groups. METHODS: Participants completed the Dysexecutive Questionnaire (DEX). RESULTS: A Rasch analysis indicated that the TBI group had significantly higher total scores on the DEX than the control group. Moreover, when compared with the control group, the students with a TBI had higher scores on all 3 subcomponents of the DEX. CONCLUSION: These findings suggest that students who endorse brain injuries may experience more difficulty with specific facets of college. Thus, the importance of academic and personal resources available for students with a TBI is discussed. PMID- 27007811 TI - Comparative Effectiveness of Etanercept and Adalimumab in Patient Reported Outcomes and Injection-Related Tolerability. AB - OBJECTIVE: To describe patient preferences in selecting specific biologics and compare clinical response using patient reported outcomes (PROs) among patients with rheumatoid arthritis (RA) started on different anti-tumor necrosis factor (TNF) therapies. METHODS: Participants were enrollees in Kaiser Permanente Northern California. Patients with RA who had at least two provider visits and started a new anti-TNF therapy from 10/2010-8/2011, were eligible for participation in this longitudinal study. Using a telephone survey, patient preferences in biologic selection and RAPID3, MDHAQ, and SF-12 scores were collected at baseline and at 6 months. Patient scores rating injection/infusion site burning and stinging (ISBS) were collected at 6 months. RESULTS: In all, 267 patients with RA responded to the baseline survey, of whom 57% preferred an injectable biologic, 22% preferred an infused biologic, and 21% had no preference. Motivation for injectable biologics was convenience (92%) and for infusion therapy was dislike or lack of self-efficacy for self-injection (16%). After 6 months of treatment with anti-TNF, 70% of the 177 patients who answered the ISBS question reported ISBS with the last dose; on a scale of 1 (none) to 10 (worst), 41% of these reported a score of 2-5; and 29% reported a score of 6-10. Adalimumab users experienced 3.2 times (95% confidence interval 1.2-8.6) the level of ISBS that etanercept users experienced. There were no significant differences in RAPID3, MDHAQ, or SF-12 scores between etanercept or adalimumab initiators. CONCLUSION: Convenience and fear of self-injection were important considerations to patients selecting a biologic drug. Although more convenient, adalimumab associated with more ISBS than did etanercept, and this rate was higher than reported in clinical trials. At 6 months, PROs did not differ between etanercept and adalimumab users. PMID- 27007813 TI - The Native Material Limit of Electron and Hole Mobilities in Semiconductor Nanowires. PMID- 27007812 TI - Aging and Sensory Substitution in a Virtual Navigation Task. AB - Virtual environments are becoming ubiquitous, and used in a variety of contexts from entertainment to training and rehabilitation. Recently, technology for making them more accessible to blind or visually impaired users has been developed, by using sound to represent visual information. The ability of older individuals to interpret these cues has not yet been studied. In this experiment, we studied the effects of age and sensory modality (visual or auditory) on navigation through a virtual maze. We added a layer of complexity by conducting the experiment in a rotating room, in order to test the effect of the spatial bias induced by the rotation on performance. Results from 29 participants showed that with the auditory cues, it took participants a longer time to complete the mazes, they took a longer path length through the maze, they paused more, and had more collisions with the walls, compared to navigation with the visual cues. The older group took a longer time to complete the mazes, they paused more, and had more collisions with the walls, compared to the younger group. There was no effect of room rotation on the performance, nor were there any significant interactions among age, feedback modality and room rotation. We conclude that there is a decline in performance with age, and that while navigation with auditory cues is possible even at an old age, it presents more challenges than visual navigation. PMID- 27007814 TI - Alcohol Expectancies Mediate the Relationship Between Age of First Intoxication and Drinking Outcomes in College Binge Drinkers. AB - BACKGROUND: While prior research has shown that age of first intoxication (AI) is associated with negative alcohol outcomes, limited research has examined factors accounting for this relationship. Alcohol expectancies, or beliefs about the effects of alcohol, may explain such associations as both positive and negative expectancies have been shown to be key predictors of drinking outcomes. OBJECTIVE: The present study examined expectancies as mediators between early AI and alcohol-related outcomes. METHOD: Data collection occurred in 2012 and 2013. Participants were college students (N = 562, 65.8% women) who completed an online survey including measures of alcohol use history, alcohol expectancies, typical alcohol consumption, and alcohol-related problems. Structural equation modeling was used to test the hypothesized model. RESULTS: Our findings support a model whereby AI is associated with drinking through its influence on both positive and negative expectancies. Specifically, an earlier AI was associated with stronger alcohol expectancies, which in turn, was associated with heavier alcohol use and alcohol-related problems. CONCLUSIONS/IMPORTANCE: These findings are consistent with expectancy theory and previous research suggesting that more experienced drinkers hold stronger drinking-related beliefs, be it positive or negative, and these expectancies ultimately explain variability in alcohol use and problems. Our findings further support that expectancies play an important role in the initiation of drinking behavior. PMID- 27007815 TI - The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis. AB - The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats. PMID- 27007816 TI - T-status and an oral fluoropyrimidine, S-1, adjuvant chemotherapy are prognostic factors in reduced-RADPLAT for resectable hypopharyngeal cancer. AB - CONCLUSION: Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit. OBJECTIVES: To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC). METHODS: Between 1999-2012, 50 patients with stage II-IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2-5 courses of IA cisplatin infusion (100 mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66-70 Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients. RESULTS: During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively. PMID- 27007817 TI - Novel Antimicrobial Peptides EeCentrocins 1, 2 and EeStrongylocin 2 from the Edible Sea Urchin Echinus esculentus Have 6-Br-Trp Post-Translational Modifications. AB - The global problem of microbial resistance to antibiotics has resulted in an urgent need to develop new antimicrobial agents. Natural antimicrobial peptides are considered promising candidates for drug development. Echinoderms, which rely on innate immunity factors in the defence against harmful microorganisms, are sources of novel antimicrobial peptides. This study aimed to isolate and characterise antimicrobial peptides from the Edible sea urchin Echinus esculentus. Using bioassay-guided purification and cDNA cloning, three antimicrobial peptides were characterised from the haemocytes of the sea urchin; two heterodimeric peptides and a cysteine-rich peptide. The peptides were named EeCentrocin 1 and 2 and EeStrongylocin 2, respectively, due to their apparent homology to the published centrocins and strongylocins isolated from the green sea urchin Strongylocentrotus droebachiensis. The two centrocin-like peptides EeCentrocin 1 and 2 are intramolecularly connected via a disulphide bond to form a heterodimeric structure, containing a cationic heavy chain of 30 and 32 amino acids and a light chain of 13 amino acids. Additionally, the light chain of EeCentrocin 2 seems to be N-terminally blocked by a pyroglutamic acid residue. The heavy chains of EeCentrocins 1 and 2 were synthesised and shown to be responsible for the antimicrobial activity of the natural peptides. EeStrongylocin 2 contains 6 cysteines engaged in 3 disulphide bonds. A fourth peptide (Ee4635) was also discovered but not fully characterised. Using mass spectrometric and NMR analyses, EeCentrocins 1 and 2, EeStrongylocin 2 and Ee4635 were all shown to contain post-translationally brominated Trp residues in the 6 position of the indole ring. PMID- 27007818 TI - Multiparametric MRI of the prostate: diagnostic performance and interreader agreement of two scoring systems. AB - OBJECTIVE: To compare the diagnostic accuracies and interreader agreements of the Prostate Imaging Reporting and Data System (PI-RADS) v. 2 and University of California San Francisco (UCSF) multiparametric prostate MRI scale for diagnosing clinically significant prostate cancer. METHODS: This institutional review board approved retrospective study included 49 males who had 1.5 T endorectal MRI and prostatectomy. Two radiologists scored suspicious lesions on MRI using PI-RADS v. 2 and the UCSF scale. Percent agreement, 2 * 2 tables and the area under the receiver operating characteristic curves (Az) were used to assess and compare the individual and overall scores of these scales. Interreader agreements were estimated with kappa statistics. RESULTS: Reader 1 (R1) detected 78 lesions, and Reader 2 (R2) detected 80 lesions. Both identified 52 of 65 significant cancers. The Az for PI-RADS v. 2 and UCSF scale for R1 were 0.68 and 0.69 [T2 weighted imaging (T2WI)], 0.75 and 0.68 [diffusion-weighted imaging (DWI)] and 0.64 and 0.72 (overall score), respectively, and were 0.72 and 0.75 (T2WI), 0.73 and 0.67 (DWI) and 0.66 and 0.75 (overall score) for R2. The dynamic contrast-enhanced percent agreements between scales were 100% (R1) and 95% (R2). PI-RADS v. 2 DWI of R1 performed better than UCSF DWI (Az = 0.75 vs Az = 0.68; p = 0.05); no other differences were found. The interreader agreements were higher for PI-RADS v. 2 (T2WI: 0.56 vs 0.42; DWI: 0.60 vs 0.46; overall: 0.61 vs 0.42). The UCSF approach to derive the overall PI-RADS v. 2 scores increased the Az for the identification of significant cancer (R1 to 0.76, p < 0.05; R2 to 0.71, p = 0.35). CONCLUSION: Although PI-RADS v. 2 DWI score may have a higher discriminatory performance than the UCSF scale counterpart to diagnose clinically significant cancer, the utilization of the UCSF scale weighing system for the integration of PI-RADS v. 2 individual parameter scores improved the accuracy its overall score. ADVANCES IN KNOWLEDGE: PI-RADS v. 2 is moderately accurate for the identification of clinically significant prostate cancer, but the utilization of alternative approaches to derive the overall PI-RADS v. 2 score, including the one used by the UCSF system, may improve its diagnostic accuracy. PMID- 27007828 TI - The Role of a Single Angiogenesis Inhibitor in the Treatment of Recurrent Glioblastoma Multiforme: A Meta-Analysis and Systematic Review. AB - BACKGROUND: Currently, the standard treatment for newly diagnosed glioblastoma multiforme (GBM) is maximal safe surgical resection followed by radiation therapy with concurrent and adjuvant temozolomide. However, disease recurs in almost all patients, and the optimal salvage treatment for recurrent GBM remains unclear. We conducted a systematic review and meta-analysis of published clinical trials to assess the efficacy and toxicities of angiogenesis inhibitors alone as salvage treatment in these patients. METHODS: Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). Demographic data, treatment regimens, objective response rate (ORR), median progression-free survival (PFS), median overall survival (OS), 6-months PFS rate, 1-year OS and grade 3/4 toxicities were extracted. We also compared the main outcomes of interest between bevacizumab and other angiogenesis inhibitors. All analyses were performed using Comprehensive Meta Analysis software (Version 2.0). RESULTS: A total of 842 patients were included for analysis: 343 patients were treated with bevacizumab, 386 with other angiogenesis inhibitors and 81 with thalidomide. The pooled ORR, 6-months PFS, and 1-year OS for recurrent GBM patients receiving angiogenesis inhibitors was 20.1%, 19.5% and 29.3%, respectively. The use of single agent bevacizumab in recurrent GBM significantly improved ORR and 6-months PFS when compared to other angiogenesis inhibitors [relative risk (RR) 2.93, 95% CI 1.38-6.21; p = 0.025; and RR 2.36 95% CI 1.46 3.82; p<0.001, respectively], while no significant difference in 1-year OS was found between the two groups (p = 0.07). when compared to thalidomide, bevacizumab treatment in recurrent GBM significantly improved ORR (RR 6.8, 95%CI: 2.64-17.6, p<0.001), but not for 6-months PFS (p = 0.07) and 1-year OS (p = 0.31). As for grade 3/4 toxicities, the common toxicity was hypertension with pooled incidence of 12.1%, while high-grade thromboembolic events (2.2%), hemorrhage (5.1%) and GI perforation (2.8%) associated with angiogenesis inhibitors were relatively low. CONCLUSIONS: In comparison with other angiogenesis inhibitors and thalidomide, the use of single agent bevacizumab as salvage treatment for recurrent GBM patients improve ORR and 6-months PFS, but not for 1-year OS. PMID- 27007819 TI - The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota. PMID- 27007829 TI - Kinetics of Monoclonal Antibody Aggregation from Dilute toward Concentrated Conditions. AB - Gaining understanding on the aggregation behavior of proteins under concentrated conditions is of both fundamental and industrial relevance. Here, we study the aggregation kinetics of a model monoclonal antibody (mAb) under thermal stress over a wide range of protein concentrations in various buffer solutions. We follow experimentally the monomer depletion and the aggregate growth by size exclusion chromatography with inline light scattering. We describe the experimental results in the frame of a kinetic model based on population balance equations, which allows one to discriminate the contributions of the conformational and of the colloidal stabilities to the global aggregation rate. Finally, we propose an expression for the aggregation rate constant, which accounts for solution viscosity, protein-protein interactions, as well as aggregate compactness. All these effects can be quantified by light scattering techniques. It is found that the model describes well the experimental data under dilute conditions. Under concentrated conditions, good model predictions are obtained when the solution pH is far below the isoelectric point (pI) of the mAb. However, peculiar effects arise when the solution pH is increased toward the mAb pI, and possible explanations are discussed. PMID- 27007831 TI - Association of the chromosome 11p13.5 variant and atopic dermatitis with a family history of atopy in the Chinese Han population. AB - BACKGROUND: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations. OBJECTIVE: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population. METHODS: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform. Data were analyzed with PLINK 1.07 software. RESULTS: We found that rs12634229 (3q13.2), rs7927894 (11p13.5) and rs878860 (11p15.4) showed a slight association with AD (P = 0.012, P = 0.033, P = 0.020, respectively); rs6780220 (3p21.33) was preferentially related to AD with keratosis pilaris, but did not reach the threshold of significance after correction. The frequency of rs7927894 allele T was significantly different between AD patients with a positive and negative family history of atopy. CONCLUSION: The loci rs7927894 (11p13.5) are related to AD with a positive family history of atopy in Chinese Han population, providing novel insight into the genetic pathogenesis of AD. PMID- 27007830 TI - Atopic dermatitis: recent insight on pathogenesis and novel therapeutic target. AB - Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It affects infancy, but it is also highly prevalent in adults and it is one of the disease burdens for the patients and their families. Nowadays, AD is recognized as a heterogenous disease with different subtypes with variable clinical manifestations which is affected by the impairments of the skin barrier. The severity of AD dictates the level of treatment. Current AD treatment focuses on restoration of the barrier function, mainly through the use of moisturizers and corticosteroids to control the inflammation, topical calcineurin inhibitors, and immunosuppresive drugs in the most severe cases. However, targeted disease modifying therapies are under investigation. The most recent findings on the skin microbial dysbiosis is a promising future direction for the development of new treatments. We need to improve the understanding of the complex microbiome-host interactions, the role of autoimmunity, the comparative effectiveness of therapies and the ways to appropriately implement the educational strategies. PMID- 27007832 TI - Association between interleukin-17a gene polymorphisms and asthma risk: a meta analysis. AB - BACKGROUND: Interleukin-17A (IL-17A), a proinflammatory cytokine, plays an important role in the pathogenesis of asthma. Considerable research has assessed the association between IL-17A polymorphisms and asthma risk, but the results are inconsistent. OBJECTIVE: This meta-analysis was carried out to make a more precise estimation of the relationship between IL-17A polymorphisms and asthma risk. METHODS: The PUBMED, MEDLINE, EMBASE, Chinese National Knowledge Infrastructure and Wan Fang databases were searched systemically on December 12, 2014 and data were extracted from eligible studies by two independent reviewers. Meta-analysis, sub-group analysis, sensitivity analysis and publication bias assessments were all done using Stata 12.1 software. RESULTS: The IL-17A -737C/T polymorphism and IL-17A -197G/A polymorphism were included in the analysis with seven case-control studies. Asthma patients (n = 2882) and healthy controls (n = 2093) were included. The IL17A -737C/T polymorphism was found to have a significantly protective effect on asthma in the allele model (OR = 0.86, 95% CI 0.78-0.96, P = 0.007), dominant model (OR = 0.76, 95% CI 0.65-0.88, P <0.001) and heterozygous model (OR = 0.75, 95% CI 0.64-0.88, P < 0.001) in the overall analysis. Stratified by ethnicity and age, the effects were also significant in the Asian population and in children. However, for IL-17A -197G/A, no significant association was revealed either in the overall analysis in the ethnicity-special subgroup analysis. CONCLUSIONS: The IL-17A -737C/T polymorphism is likely to contribute to protection against asthma, while the IL-17A -197G/A polymorphism may not be associated with asthma susceptibility. PMID- 27007833 TI - Association between JAK1 gene polymorphisms and susceptibility to allergic rhinitis. AB - OBJECTIVES: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Janus kinase 1 (JAK1), a member of JAK family, has recently been found to participate in the immune response and the development of allergic airway disease. This study was performed to evaluate the potential association of JAK1 polymorphisms with AR in a Chinese Han population. METHODS: A case-control study was performed in 450 Chinese AR patients and 615 healthy controls. Three SNPs in the JAK1 gene, rs3790532, rs310241 and rs2780815, were analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay (PCR RFLP). RESULTS: An association was detected between SNP rs310241 in the JAK1 gene and AR in a Chinese Han population. However, no significant association was observed between the polymorphisms rs3790532 and rs2780815 and AR. For rs310241, the CC genotype and the C allele significantly increased the risk of AR. Furthermore, we found that the ACG haplotype in JAK1 gene was positively correlated with AR, while the GTG haplotype was associated with a significantly decreased risk of AR. CONCLUSION: This study indicates that the JAK1 rs310241 C related genotype and allele are involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population. PMID- 27007834 TI - Evaluation of drug provocation tests in Korean children: a single center experience. AB - BACKGROUND: Drug provocation tests (DPTs) are difficult to perform in clinical practice, even though they are the gold standard for the diagnosis of adverse drug reactions (ADRs). OBJECTIVE: The aims of this study were to evaluate the common causative drugs of type B ADRs and to analyze the relationships between host factors and the results of DPTs in Korean children. METHODS: We retrospectively reviewed the medical records of all children younger than 19 years of age who underwent a DPT between November 1994 and November 2014. Open provocation tests were performed with non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, aminopenicillins, cephalosporins, non-beta-lactam antibiotics, antiepileptic drugs, or other drugs. RESULTS: Overall, 84 DPTs were performed in 56 patients whose median age was 7.5 years (range, 6 months to 18 years). DPTs were positive in 25 (29.8%) of 84 cases, which translated to 18 (32.1%) positive findings in 56 patients. Drugs that provided positive results included NSAIDs (7 cases, 28.0%), aminopenicillins (5 cases, 20.0%), acetaminophen (4 cases, 16.0%), cephalosporins (3 cases, 12.0%), and non-beta lactams (2 cases, 8.0%). Anaphylaxis was noted in 5 (20.0%) of 25 cases. There were no serious complications of DPTs in any of the subjects. The median age was 10.5 years for children who had a positive result following the DPT and 5.0 years for those with negative results (P value = 0.019). CONCLUSIONS: DPTs can be performed safely in children with suspected ADRs in order to achieve a correct diagnosis. PMID- 27007835 TI - Minimal clinical important difference (MCID) of the Thai Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL). AB - BACKGROUND: Chronic urticaria (CU) has negative impacts on patients' daily lives. The Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) evaluates quality of life impairment attitudes among chronic urticaria patients. Although the CU Q2oL has been validated in several languages, the minimal clinical important difference (MCID) of the CU-Q2oL has never been determined. OBJECTIVE: This study aimed to investigate the validity, reliability, responsiveness to change, and MCID of the Thai CU-Q2oL. METHODS: The Thai CU-Q2oL was translated with permission from the authors of the original Italian version. The Thai CU-Q2oL, the validated Thai Dermatology Life Quality Index (DLQI), and the Urticaria Activity Score were assessed for 166 patients to evaluate validity and internal consistency. The three questionnaires were then administered to 124 patients to determine the test-retest reliability, responsiveness, and MCID of the Thai CU Q2oL. RESULTS: The Thai CU-Q2oL contained only three domains, whereas the Italian version revealed six domains. Nevertheless, the total variance of the Thai CU Q2oL (60.5%) was very close to that of the Italian version (60.0%). The validity of the Thai CU-Q2oL was shown by strong correlations between CU-Q2oL and DLQI scores. The Thai CU-Q2oL also had high internal consistency and test-retest reliability. Distribution-based, receiver operating characteristic analysis, and anchor-based approaches yielded MCID values of 3.9-8.0, 15, and 21.1, respectively. CONCLUSIONS: The Thai CU-Q2oL is a valid and reliable instrument. We propose that a difference in the Thai CU-Q2oL score of 15 (MCID) is the smallest change patients perceive as a meaningful improvement. PMID- 27007836 TI - Analysis of solar urticaria in Thai patients. AB - BACKGROUND: Solar urticaria (SU) is an uncommon photodermatosis characterized by erythema and whealing within minutes to a few hours after exposure to sunlight or an artificial light source. OBJECTIVE: To determine the clinical features, photobiological characteristics and treatment outcomes in Thai SU patients visiting a tertiary referral hospital. METHOD: A retrospective analysis of 13 patients with SU was conducted. Demographic data, disease characters, phototesting results, laboratory investigations, treatment and outcome were evaluated. RESULTS: Of the 13 patients diagnosed with SU from 2000 to 2012, most patients were female (10, 77%). The mean age of onset was 29 years (15-51). The mean duration of SU was 46 months (6-120) at presentation. The most common affected location was the upper extremities (92%), followed by head and neck (77%). The responsible action spectra were visible light in 8 patients (61.5%), ultraviolet A (UVA) in 1 patient (8%), and both visible light and UVA in 4 patients (31%). The median course from disease onset to disease resolution was 63 months (95% confidence interval 30-95). After 13 months and 55 months from the onset of symptoms, 23% and 49% of patients, respectively, were predicted to recover from their symptoms. CONCLUSION: Solar urticaria is a rare condition in Thailand. The common eliciting spectra of SU were visible light and UVA. Management of SU remains challenging. PMID- 27007837 TI - Identification of wheat sensitization using an in-house wheat extract in Coca-10% alcohol solution in children with wheat anaphylaxis. AB - BACKGROUND: Identification of wheat sensitization by a skin prick test (SPT) is essential for children with wheat-induced anaphylaxis, since oral food challenge can cause serious adverse effects. Wheat allergens are both water/salt and alcohol soluble. The preparation of wheat extract for SPT containing both water/salt and alcohol soluble allergen is needed. OBJECTIVE: To determine if a wheat extract using Coca's solution containing 10% alcohol (Coca-10% EtOH), prepared in-house, contians both water/salt and alcohol soluble allergens. METHODS: Serum of children with a history of anaphylaxis after wheat ingestion was used. Wheat flour was extracted in Coca-10% alcohol solution. An SPT with both commercial and in-house wheat extracts was performed as well as specific IgE (sIgE) for wheat and omega-5 gliadin. Direct and IgE inhibition immunoblots were performed to determine serum sIgE levels against water/salt as well as alcohol soluble (gliadins and glutenins) allergens in the extracts. RESULTS: Six children with history of wheat anaphylaxis had positive SPT to both commercial and in house extracts. They also had different levels of sIgE against wheat and omega-5 gliadin allergens. The results of direct immunoblotting showed all tested sera had sIgE bound to ~35 kDa wheat protein. Further IgE inhibition immunoblotting identified the ~35 kDa wheat protein as gliadin but not gluten allergen. CONCLUSION: The in-house prepared Coca-10% EtOH solution could extract both water/salt and alcohol soluble allergens. The ~35 kDa gliadin appears to be a major wheat allergen among tested individuals. PMID- 27007838 TI - Validation study of the pediatric allergic rhinitis quality of life questionnaire. AB - BACKGROUND: The Paediatric Allergic Rhinitis Quality of Life Questionnaire (Ped AR-QoL) is the first tool developed for the assessment of health-related quality of life (QoL) in Greek children with allergic rhinitis (AR). OBJECTIVE: The aim of the current study was to validate the child and parent forms of the Ped-AR-QoL in children aged 6-14 years-old who suffered from AR and were followed in a pediatric allergy clinic. METHODS: The Ped-AR-QoL, which was completed by 112 children and their parents, was correlated to the generic QoL questionnaire (Disabkids), which is already valid in Greece for children with chronic disorders, as well as with expert opinions on the severity of disease. RESULTS: The Ped-AR-QoL child and parent forms had very good internal consistency (alpha values of 0.797 and 0.872, respectively), while there was a moderate positive correlation of the disease-specific questionnaire with most of the subscales of the generic questionnaire. There has been a statistically significant association between the Ped-AR-QoL and the expert perception of disease severity. CONCLUSIONS: The Ped-AR-QoL had very good reliability and convergent validity when compared with the generic Disabkids QoL. The significance of the association between the disease-specific questionnaire and the expert opinion is an important finding validating the questionnaire. The Ped-AR-QoL may become a helpful tool which can be used in everyday clinical practice by clinicians and it may also be used for assessing therapeutic interventions in clinical trials. PMID- 27007839 TI - Would mean platelet volume/platelet count ratio be used as a novel formula to predict 22q11.2 deletion syndrome? AB - BACKGROUND: The diagnosis of 22q11.2 deletion syndrome depends on a time consuming and expensive method, fluorescence in situ hybridisation (FISH). OBJECTIVES: We aimed to determine new parameters which can aid for in the diagnosis of 22q11.2 deletion syndrome. METHODS: Twenty two patients with 22q11.2 or 10p13 deletion were evaluated retrospectively. RESULTS: Facial-dysmorphism and mental-motor retardation were detected in 100% of patients. Mean platelet (PLT) counts were lower (224,980 versus 354,000, p = 0.001), mean PLT volume (MPV) (9.95 versus 7.07, p = 0.002), and MPV/PLTx105 ratios (5.36 versus 2.08, p < 0.001) were higher in patients with 22q11.2 deletion compared with the control group. Area under the receiver-operator characteristic (ROC) curve was 0.864, sensitivity was 84.6%, specificity was 90.9%, positive predictive value (PPV) was 91.7%, and negative predictive value (NPV) was 83.3% when MPV was 8.6. Area under ROC curve was 0.864, sensitivity was 76.9%, specificity was 90.1%, PPV was 90.1%, and NPV was 76.3% when PLT was 265,500. Area under ROC curve was 0.906, sensitivity was 84.6%, specificity was 100%, PPV was 100%, and NPV was 84.6% when MPV/PLTx105 was 3.3. Expression of PLT surface markers which were not in the GPIb V-IX receptor complex (CD61, CD41a) increased as the surface area increased, but markers which were in a complex (CD42a, CD42b) did not change. CONCLUSIONS: High MPV/PLT value can be a good predictor for the diagnosis of 22q11.2 deletion syndrome. We suggest that in patients with facial dysmorphism and retardation in neurodevelopmental milestones and if MPV>=8.6fl, MPV/PLTx105 ratio>=3.3 and PLT count <=265,500/mm3, the patients should be tested by FISH analysis to confirm the 22q11.2 deletion. If there are no macrothrombocytes, the 10p13 deletion should be tested in suspected cases. PMID- 27007840 TI - A 10-year retrospective study of neonatal lupus erythematous in China. AB - BACKGROUND: Neonatal lupus erythematosus (NLE) is not a common disease. The death rate of complete congenital heart block (CCHB), which is the most severe clinical manifestation, is as high as 20% to 30%, so early recognition of infants at risk is important. OBJECTIVES: To investigate the clinical features and long-term prognosis of NLE. METHODS: Twenty-five cases with NLE were reviewed. The clinical manifestations of patients and their mothers were summarized and analyzed. Autoantibodies were detected, and long-term follow-up was carried out. RESULTS: There were 25 patients (male:female ratio of 11:14). CCHB was detected in only 3 of the 25 patients (12%). Cutaneous neonatal lupus erythematosus (CNLE) was seen in 22 of the 25 patients (88%). Eight babies were treated with intravenous immunoglobulin (IVIG), five of whom had a prolonged PR interval that reverted to normal sinus rhythm. During the follow-up of the patients, we found only two patients with CCHB without a pacemaker, who both exhibited growth delay. One patient with CCHB without a pacemaker died. CONCLUSIONS: Children with NLE have an excellent outcome when only skin lesions are present. Even the hepatic, hematological and neurological abnormalities are transient, with generally good outcomes. IVIG might have some effectiveness due to enhanced anti-inflammatory activity to treat early diseases that may be reversible (e.g. prolonged PR interval). The long-term prognosis for patients with NLE is still under investigation, and some infants with NLE may progress to other autoimmune diseases later in childhood. PMID- 27007841 TI - Primary cilia are not calcium-responsive mechanosensors. AB - Primary cilia are solitary, generally non-motile, hair-like protrusions that extend from the surface of cells between cell divisions. Their antenna-like structure leads naturally to the assumption that they sense the surrounding environment, the most common hypothesis being sensation of mechanical force through calcium-permeable ion channels within the cilium. This Ca(2+)-responsive mechanosensor hypothesis for primary cilia has been invoked to explain a large range of biological responses, from control of left-right axis determination in embryonic development to adult progression of polycystic kidney disease and some cancers. Here we report the complete lack of mechanically induced calcium increases in primary cilia, in tissues upon which this hypothesis has been based. We developed a transgenic mouse, Arl13b-mCherry-GECO1.2, expressing a ratiometric genetically encoded calcium indicator in all primary cilia. We then measured responses to flow in primary cilia of cultured kidney epithelial cells, kidney thick ascending tubules, crown cells of the embryonic node, kinocilia of inner ear hair cells, and several cell lines. Cilia-specific Ca(2+) influxes were not observed in physiological or even highly supraphysiological levels of fluid flow. We conclude that mechanosensation, if it originates in primary cilia, is not via calcium signalling. PMID- 27007842 TI - Neuroscience: Untangling autism. PMID- 27007843 TI - Corrigendum: An observational radiative constraint on hydrologic cycle intensification. PMID- 27007844 TI - Thalamic reticular impairment underlies attention deficit in Ptchd1(Y/-) mice. AB - Developmental disabilities, including attention-deficit hyperactivity disorder (ADHD), intellectual disability (ID), and autism spectrum disorders (ASD), affect one in six children in the USA. Recently, gene mutations in patched domain containing 1 (PTCHD1) have been found in ~1% of patients with ID and ASD. Individuals with PTCHD1 deletion show symptoms of ADHD, sleep disruption, hypotonia, aggression, ASD, and ID. Although PTCHD1 is probably critical for normal development, the connection between its deletion and the ensuing behavioural defects is poorly understood. Here we report that during early post natal development, mouse Ptchd1 is selectively expressed in the thalamic reticular nucleus (TRN), a group of GABAergic neurons that regulate thalamocortical transmission, sleep rhythms, and attention. Ptchd1 deletion attenuates TRN activity through mechanisms involving small conductance calcium dependent potassium currents (SK). TRN-restricted deletion of Ptchd1 leads to attention deficits and hyperactivity, both of which are rescued by pharmacological augmentation of SK channel activity. Global Ptchd1 deletion recapitulates learning impairment, hyper-aggression, and motor defects, all of which are insensitive to SK pharmacological targeting and not found in the TRN restricted deletion mouse. This study maps clinically relevant behavioural phenotypes onto TRN dysfunction in a human disease model, while also identifying molecular and circuit targets for intervention. PMID- 27007845 TI - Nucleus accumbens D2R cells signal prior outcomes and control risky decision making. AB - A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making- either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real time risky decision-making, can be largely explained by the encoding in D2R expressing NAc cells of prior unfavourable outcomes during decision-making. PMID- 27007847 TI - Corrigendum: Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. PMID- 27007846 TI - Structure of promoter-bound TFIID and model of human pre-initiation complex assembly. AB - The general transcription factor IID (TFIID) plays a central role in the initiation of RNA polymerase II (Pol II)-dependent transcription by nucleating pre-initiation complex (PIC) assembly at the core promoter. TFIID comprises the TATA-binding protein (TBP) and 13 TBP-associated factors (TAF1-13), which specifically interact with a variety of core promoter DNA sequences. Here we present the structure of human TFIID in complex with TFIIA and core promoter DNA, determined by single-particle cryo-electron microscopy at sub-nanometre resolution. All core promoter elements are contacted by subunits of TFIID, with TAF1 and TAF2 mediating major interactions with the downstream promoter. TFIIA bridges the TBP-TATA complex with lobe B of TFIID. We also present the cryo electron microscopy reconstruction of a fully assembled human TAF-less PIC. Superposition of common elements between the two structures provides novel insights into the general role of TFIID in promoter recognition, PIC assembly, and transcription initiation. PMID- 27007848 TI - Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. AB - Targeted, temporally regulated neural modulation is invaluable in determining the physiological roles of specific neural populations or circuits. Here we describe a system for non-invasive, temporal activation or inhibition of neuronal activity in vivo and its use to study central nervous system control of glucose homeostasis and feeding in mice. We are able to induce neuronal activation remotely using radio waves or magnetic fields via Cre-dependent expression of a GFP-tagged ferritin fusion protein tethered to the cation-conducting transient receptor potential vanilloid 1 (TRPV1) by a camelid anti-GFP antibody (anti-GFP TRPV1). Neuronal inhibition via the same stimuli is achieved by mutating the TRPV1 pore, rendering the channel chloride-permeable. These constructs were targeted to glucose-sensing neurons in the ventromedial hypothalamus in glucokinase-Cre mice, which express Cre in glucose-sensing neurons. Acute activation of glucose-sensing neurons in this region increases plasma glucose and glucagon, lowers insulin levels and stimulates feeding, while inhibition reduces blood glucose, raises insulin levels and suppresses feeding. These results suggest that pancreatic hormones function as an effector mechanism of central nervous system circuits controlling blood glucose and behaviour. The method we employ obviates the need for permanent implants and could potentially be applied to study other neural processes or used to regulate other, even dispersed, cell types. PMID- 27007850 TI - Molecular biology: Breaks in the brain. PMID- 27007849 TI - NOD1 and NOD2 signalling links ER stress with inflammation. AB - Endoplasmic reticulum (ER) stress is a major contributor to inflammatory diseases, such as Crohn disease and type 2 diabetes. ER stress induces the unfolded protein response, which involves activation of three transmembrane receptors, ATF6, PERK and IRE1alpha. Once activated, IRE1alpha recruits TRAF2 to the ER membrane to initiate inflammatory responses via the NF-kappaB pathway. Inflammation is commonly triggered when pattern recognition receptors (PRRs), such as Toll-like receptors or nucleotide-binding oligomerization domain (NOD) like receptors, detect tissue damage or microbial infection. However, it is not clear which PRRs have a major role in inducing inflammation during ER stress. Here we show that NOD1 and NOD2, two members of the NOD-like receptor family of PRRs, are important mediators of ER-stress-induced inflammation in mouse and human cells. The ER stress inducers thapsigargin and dithiothreitol trigger production of the pro-inflammatory cytokine IL-6 in a NOD1/2-dependent fashion. Inflammation and IL-6 production triggered by infection with Brucella abortus, which induces ER stress by injecting the type IV secretion system effector protein VceC into host cells, is TRAF2, NOD1/2 and RIP2-dependent and can be reduced by treatment with the ER stress inhibitor tauroursodeoxycholate or an IRE1alpha kinase inhibitor. The association of NOD1 and NOD2 with pro inflammatory responses induced by the IRE1alpha/TRAF2 signalling pathway provides a novel link between innate immunity and ER-stress-induced inflammation. PMID- 27007851 TI - Neuroscience: Making risk-takers settle. PMID- 27007852 TI - Cell biology: Calcium contradictions in cilia. PMID- 27007853 TI - Nineteen-step total synthesis of (+)-phorbol. AB - Phorbol, the flagship member of the tigliane diterpene family, has been known for over 80 years and has attracted attention from many chemists and biologists owing to its intriguing chemical structure and the medicinal potential of phorbol esters. Access to useful quantities of phorbol and related analogues has relied on isolation from natural sources and semisynthesis. Despite efforts spanning 40 years, chemical synthesis has been unable to compete with these strategies, owing to its complexity and unusual placement of oxygen atoms. Purely synthetic enantiopure phorbol has remained elusive, and biological synthesis has not led to even the simplest members of this terpene family. Recently, the chemical syntheses of eudesmanes, germacrenes, taxanes and ingenanes have all benefited from a strategy inspired by the logic of two-phase terpene biosynthesis in which powerful C-C bond constructions and C-H bond oxidations go hand in hand. Here we implement a two-phase terpene synthesis strategy to achieve enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3 carene. The purpose of this synthesis route is not to displace isolation or semisynthesis as a means of generating the natural product per se, but rather to enable access to analogues containing unique placements of oxygen atoms that are otherwise inaccessible. PMID- 27007854 TI - The conformational signature of beta-arrestin2 predicts its trafficking and signalling functions. AB - Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters to monitor conformational changes in beta-arrestin2, here we show that GPCRs impose distinctive arrestin 'conformational signatures' that reflect the stability of the receptor-arrestin complex and role of beta-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in beta-arrestin2 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average beta-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function. PMID- 27007856 TI - Design of Multiple Logic Gates Based on Chemically Triggered Fluorescence Switching of Functionalized Polyethylenimine. AB - In this study, two new functionalized polyethylenimine (PEI), PEIR and PEIQ, have been synthesized by covalently conjugating rhodamine 6G (R6G) or 8-chloroacetyl aminoquinoline (CAAQ) and have been investigated for their sensing capabilities toward metal ions and anions basing on fluorescence on-off and off-on mechanisms. When triggered by protons, metal ions, or anions, functionalized PEIs can behave as a fluorescence switch, leading to a multiaddressable system. Inspired by these results, functionalized PEI-based logic systems capable of performing elementary logic operations (YES, NOT, NOR, and INHIBIT) and integrative logic operations (OR + INHIBIT) have been constructed by observing the change in the fluorescence with varying the chemical inputs such as protons, metal ions, and anions. Due to its characteristics, such as high sensitivity and fast response, developing functionalized PEI as a new material to perform logic operations may pave a new avenue to construct the next generation of molecular devices with better applicability for biomedical research. PMID- 27007855 TI - beta-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle. AB - (beta-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs). They bind to active, phosphorylated GPCRs and thereby shut off 'classical' signalling to G proteins, trigger internalization of GPCRs via interaction with the clathrin machinery and mediate signalling via 'non-classical' pathways. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) beta-arrestin proteins (beta-arrestin1 and beta-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (beta-)arrestins that have recently been solved by X-ray crystallography. Here we investigate both the interaction of beta-arrestin with GPCRs, and the beta-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET) based beta-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in beta-arrestin2 that occur rapidly after the receptor beta-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor type-specific, two-step binding and activation process between GPCRs and beta arrestins. They further indicate that beta-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of beta-arrestins, which permits their active signalling. PMID- 27007857 TI - Respiratory and gastrointestinal dysfunctions associated with auriculo-condylar syndrome and a homozygous PLCB4 loss-of-function mutation. AB - Auriculo-Condylar Syndrome (ACS) is a craniofacial malformation syndrome characterized by external ear anomalies, hypoplasia of the mandibular condyle, temporomandibular joint abnormalities, micrognathia, and microstomia. Glossoptosis, masticatory abnormalities, orthodontic problems, and malocclusion occur in a majority of affected subjects. The clinical diagnosis is usually suggested by the pathognomonic ear appearance ("question mark ear"), consisting of a variable degree of clefting between the helix and earlobe. The genetic mechanisms underlying ACS have recently been identified. Both autosomal dominant and recessive inheritance of mutations in phospholipase C, beta 4 (PLCB4) and endothelin 1 (EDN1) have been reported along with autosomal dominant mutations in guanine nucleotide-binding protein (G protein) alpha inhibiting activity polypeptide 3 (GNAI3). We report 6 years of follow-up of a child with a clinical phenotype consistent with ACS due to a homozygous frameshift mutation in PLCB4. The baby presented feeding difficulties associated with failure to thrive and a complex sleep-related respiratory disorder, characterized by central and obstructive apnoeas. Our observations of this case further delineate the phenotype of ACS associated with autosomal recessive PLCB4 loss-of-function mutations, underscoring gastrointestinal dysfunction and severe sleep-related breathing abnormalities as additional features when compared to patients with heterozygous mutations with a presumed dominant negative effect. (c) 2016 Wiley Periodicals, Inc. PMID- 27007858 TI - Further studies to evaluate methods of leucoreduction to prevent alloimmune platelet refractoriness and induce tolerance in a dog platelet transfusion model. AB - OBJECTIVES: Three leucoreduction filters were evaluated - when used alone or combined with centrifuge leucoreduction (C-LR) - to prevent alloimmune platelet refractoriness in a dog platelet transfusion model. MATERIALS AND METHODS: Donor platelet-rich plasma (PRP) or buffy coat (BC) platelets were either filter leucoreduced (F-LR) or F-LR/C-LR, (51) Cr radiolabelled and transfused. Weekly transfusions were given for up to 8 weeks or until platelet refractoriness. Recipients who accepted treated transfusions were then given non-leucoreduced (non-LR) platelets to determine whether donor-specific tolerance had been induced. RESULTS: Acceptance of F-LR PRP transfusions ranged from 29% to 66%. F LR/C-LR transfusions prepared from PRP were accepted by 92%, from BC by 63% and from pooled PRP by 75% of recipients (p=NS); overall acceptance rate of F-LR/C-LR transfusions was 83%. Tolerance to subsequent non-LR transfusions occurred in 45% of the F-LR-/C-LR-accepting recipients unrelated to DR-B compatibility between donors and recipients (P = 0.18). CONCLUSION: In a dog platelet transfusion model, acceptance of donor platelets required combining F-LR with C-LR as apparently each process removes different immunizing WBCs. PMID- 27007859 TI - Joint modeling of longitudinal and survival data with the Cox model and two-phase sampling. AB - A common objective of cohort studies and clinical trials is to assess time varying longitudinal continuous biomarkers as correlates of the instantaneous hazard of a study endpoint. We consider the setting where the biomarkers are measured in a designed sub-sample (i.e., case-cohort or two-phase sampling design), as is normative for prevention trials. We address this problem via joint models, with underlying biomarker trajectories characterized by a random effects model and their relationship with instantaneous risk characterized by a Cox model. For estimation and inference we extend the conditional score method of Tsiatis and Davidian (Biometrika 88(2):447-458, 2001) to accommodate the two phase biomarker sampling design using augmented inverse probability weighting with nonparametric kernel regression. We present theoretical properties of the proposed estimators and finite-sample properties derived through simulations, and illustrate the methods with application to the AIDS Clinical Trials Group 175 antiretroviral therapy trial. We discuss how the methods are useful for evaluating a Prentice surrogate endpoint, mediation, and for generating hypotheses about biological mechanisms of treatment efficacy. PMID- 27007860 TI - An integrated interface for peripheral neural system recording and stimulation: system design, electrical tests and in-vivo results. AB - The prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of 2 integrated circuits: a standard CMOS device for neural recording and a HVCMOS device for neural stimulation. The integrated circuits have been realized in 2 different 0.35MU m CMOS processes available from ams. The complete system incorporates 8 channels each including the analog front-end, the A/D conversion, based on a sigma delta architecture and a programmable stimulation module implemented as a 5-bit current DAC; two voltage boosters supply the output stimulation stage with a programmable voltage scalable up to 17V. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7MU V r m s , and to selectively elicit the tibial and plantar muscles using different active sites of the electrode. PMID- 27007861 TI - Increasing the qualitative understanding of optimal functionality in older adults: a focus group based study. AB - BACKGROUND: Decreased independence and loss of functional ability are issues regarded as inevitably connected to old age. This ageism may have negative influences on older adults' beliefs about aging, making it difficult for them to focus on their current ability to maintain a good health. It is therefore important to change focus towards promoting Optimal Functionality (OF). OF is a concept putting the older adult's perspective on health and function in focus, however, the concept is still under development. Hence, the aim was to extend the concept of optimal functionality in various groups of older adults. METHODS: A qualitative study was conducted based on focus group discussions (FGD). In total 6 FGDs were performed, including 37 older adults from three different groups: group 1) senior athletes, group 2) free living older adults, group 3) older adults living in senior living homes. All data was transcribed verbatim and analyzed following the process of deductive content analysis. RESULTS: The principal outcome of the analysis was "to function as optimally as you possibly can", which was perceived as the core of the concept. Further, the concept of OF was described as multifactorial and several new factors could be added to the original model of OF. Additionally the findings of the study support that all three cornerstones comprising OF have to occur simultaneously in order for the older adult to function as optimal as possible. CONCLUSIONS: OF is a multifaceted and subjective concept, which should be individually defined by the older adult. This study further makes evident that older adults as a group are heterogeneous in terms of their preferences and views on health and should thus be approached as such in the health care setting. Therefore it is important to promote an individualized approach as a base when caring for older adults. PMID- 27007862 TI - Letter to the Editor: Acute extrahepatic infectious or inflammatory diseases are a cause of transient mosaic pattern on CT and MR imaging related to sinusoidal dilatation of the liver. PMID- 27007863 TI - Response: Transient liver modifications associated with abdominal sepsis are various and underestimated. PMID- 27007864 TI - Discovering phenotypic causal structure from nonexperimental data. AB - The evolutionary potential of organisms depends on how their parts are structured into a cohesive whole. A major obstacle for empirical studies of phenotypic organization is that observed associations among characters usually confound different causal pathways such as pleiotropic modules, interphenotypic causal relationships and environmental effects. The present article proposes causal search algorithms as a new tool to distinguish these different modes of phenotypic integration. Without assuming an a priori structure, the algorithms seek a class of causal hypotheses consistent with independence relationships holding in observational data. The technique can be applied to discover causal relationships among a set of measured traits and to distinguish genuine selection from spurious correlations. The former application is illustrated with a biological data set of rat morphological measurements previously analysed by Cheverud et al. (Evolution 1983, 37, 895). PMID- 27007865 TI - Aneurysmal bone cyst of C2 treated with novel anterior reconstruction and stabilization. AB - PURPOSE: Aneurysmal bone cysts (ABC) form 1 % of primary bone tumors. Reported incidence rates are no more than 1.4 to 1,00,000. ABC of spine frequently involves posterior elements and commonly affects the lumbar spine (45 %). We present a case of C2 ABC for the challenges it poses due to the rarity of the lesion, tedious to access location, dilemmas relating to the suitable approach for tumor resection and technically demanding stabilization and reconstruction strategy post resection. METHODS: Clinical data analysis was performed to discuss a method of novel anterior column reconstruction following resection of a C2 aneurysmal bone cyst in a 8 year old child with anterior and posterior elements being involved. RESULTS: An 8-year-old girl with an aneurysmal bone cyst of the C2 vertebra underwent staged surgery following pre-operative embolisation. First a posterior approach tumor excision with posterior instrumented fusion was performed. Following which, using a modified anterior retropharyngeal approach anterior tumor excision and fibular graft reconstruction between the C1 lateral mass and C2 body was performed. Complete tumor clearance and stable reconstruction was successfully achieved in our patient. Patient showed excellent clinical outcome with radiological fusion. CONCLUSIONS: Preoperative embolisation in the treatment of ABC has supplemental advantage by reducing blood loss. Modified anterior retropharyngeal approach allows satisfactory clearance for C1-2 lesion and fibular strut graft between the C1 lateral mass and C2 body can provide a stable graft placement with good chance of fusion. Instability and spinal deformity, whether preexisting or post-excision, should be corrected with reconstruction and stabilization to offer best chance of cure in such cases. PMID- 27007866 TI - Performance Evaluation of the New HIV-1 Quantification Assay, Xpert HIV-1 Viral Load, on a Wide Panel of HIV-1 Variants. AB - OBJECTIVE: To evaluate the quantification performance of the new Cepheid GeneXpert HIV-1 viral load assay, on a wide panel of HIV-1 variants. METHODS: Clinical performance was evaluated relative to the Abbott RealTime HIV-1 assay on 285 HIV-1 seropositive samples selected to cover the assays quantification range (40 copies/mL-10,000,000 copies/mL), and included RNA undetectable or detected seropositive samples. The panel comprised 120 subtype B, 150 non-B, and 15 nontypable clinical samples; serial dilutions of 18 viral supernatants representative of the divergent viruses of HIV-1 groups N, O, and P were also tested. RESULTS: Based on samples selected according to the Abbott assay viral loads (VL), the Cepheid assay detected or quantified 222/285 (78%) samples and the Abbott assay 240/285 (84%). Xpert yielded VLs for 162 (76%) of the 213 quantifiable samples with Abbott. This difference corresponded to 51 samples with VL >40 copies/mL by the Abbott assay (all below 200 copies/mL) but detected (n = 40) or undetectable (n = 11) by the Cepheid assay. VL of samples quantifiable by both assays (n = 162) showed very strong correlation, with a Spearman correlation coefficient of 0.985 and a Bland-Altman's mean of differences of -0.01. Performance for quantification of the non-M samples showed very good correlation, with significantly higher values with Cepheid for the group N and 2 group O samples. CONCLUSIONS: Our study showed that the Xpert HIV-1 VL assay offered very good performance for detection and quantification of the current HIV-1 genetic diversity; differences reported at the threshold could be an issue and requires further evaluations. The practicability of this new assay makes it suitable for low-income countries, where it could facilitate and improve follow-up of patients, as well as for high-income regions. PMID- 27007867 TI - Elimination of NTproBNP in peritoneal dialysis patients. Does peritoneal membrane type make a difference in plasma level and elimination of NTproBNP? AB - BACKGROUND: Brain natriuretic peptide and its derivative peptide NTproBNP are utilized to exclude cardiac diseases, and predicting risk of mortality in dialysis patients. Our aim was to evaluate both elimination of NTproBNP through dialysate and a possible relationship between plasma and/or dialysate NTproBNP level and membrane transport status of peritoneal dialysis patients. METHODS: 57 plasma (P) and dialysate (D) samples of 44 peritoneal dialysis (PD) patients were analyzed for NTproBNP. Modified peritoneal equilibration test (PET) results and other variables were obtained from the charts. RESULTS: Median (IQR) NTproBNP concentrations (pg/mL * 1,000) in P and D were 3.3 (1 - 13) and 0.5 (0.2 - 3.6), respectively. There was a linear correlation between P-NTproBNP and D-NTproBNP (r = 0.928, p = 0.0001; regression equation was y = 0.897*x -0.28). Mean P/D NTproBNP ratio was 5.5 +/- 0.5. Median P and D-NTproBNP levels by the membrane transport status were aligned as high (H) > high average (HA) > low average (LA), and the difference between H and LA was statistically significant (p < 0.001). Mean arterial pressure (MAP), residual Kt/V and dialysate/plasma ratio of crearinine (D/P Cr) were significant predictors of D-NTproBNP; whereas only MAP and residual Kt/V were significant predictors of P-NTproBNP in multiple regression analysis. Both P- and D-NTproBNP have significant and similar size of correlations with MAP, albumin, D/P Cr ratio, and Na. CONCLUSIONS: D-NTproBNP level is ~ 1/5 of P-NTproBNP, and the issue of relationship between membrane transport status and natriuretic peptide levels needs more work. PMID- 27007868 TI - Claudin 19-based familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a sibling pair. AB - BACKGROUND: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare, autosomal recessive condition caused by mutations in CLDN16 or CLDN19, which encode for tight junction proteins, claudin-16 and claudin-19, respectively. This condition often has a delayed diagnosis in patients with no prior family history due to a lack of specific clinical symptoms. Description of case, diagnosis, and treatment: A 4-year, 10-month-old Caucasian boy presented with failure to thrive, developmental delay, and ocular findings consisting of horizontal nystagmus, bilateral macular staphylomas, and high myopia. Laboratory studies revealed hypercalciuria, hypomagnesemia, and renal insufficiency. Renal ultrasound showed bilateral small kidneys with medullary nephrocalcinosis. Candidate gene sequencing performed at age 7 years identified a novel, homozygous, frameshift mutation c.140_141delAT (p.Tyr47Stop) within CLDN19, confirming the molecular diagnosis of FHHNC. Due to rapid renal progression, the proband underwent renal transplant at age 10 years, 10 months. FHHNC was prenatally diagnosed in the proband's sister, who was found at birth to have ocular findings and hypomagnesemia. In addition, she had feeding intolerance and persistent hypoglycemia with hyperinsulinism that has required chronic diazoxide therapy. CONCLUSIONS: Although rare, FHHNC should be suspected in patients who present with nephrocalcinosis in the setting of congenital eye anomalies.. PMID- 27007869 TI - Care and outcomes of end-stage kidney disease patients in times of armed conflict: recommendations for action. AB - BACKGROUND: Conflicts can lead to significant disruption in the care of endstage kidney disease (ESKD) patients. The purpose of this paper is to review the available literature on the care of ESKD patients in times of armed conflict and make recommendations for action. METHOD: A review of all PubMed-published reports between 1965 and 2015 about the care of ESKD patients at the time of conflict. We excluded articles that reported on acute kidney injury and natural disasters. RESULTS: We found a total of 12 reports on dialysis care and/or kidney transplant care from five armed conflicts and resulting refugee crises. These conflicts led to significant shortage of staff and resources and caused several obstacles in providing adequate dialysis to ESKD patients. In one study, the mortality rate of patients on automated peritoneal dialysis was as high as 95%. The kidney transplantation rate decreased in all but one of the reports about kidney transplant care and patients had difficulties securing their immunosuppressive medications. CONCLUSIONS: ESKD patients, especially dialysis patients, comprise a severely vulnerable population during conflicts. Their care can be disrupted and altered leading to a substantial increase in their mortality rate. Efforts to improve their care during conflicts are needed. PMID- 27007870 TI - Near-drowning related acute kidney injury. PMID- 27007871 TI - Identification of Adenine and Benzimidazole Nucleosides as Potent Human Concentrative Nucleoside Transporter 2 Inhibitors: Potential Treatment for Hyperuricemia and Gout. AB - To test the hypothesis that inhibitors of human concentrative nucleoside transporter 2 (hCNT2) suppress increases in serum urate levels derived from dietary purines, we previously identified adenosine derivative 1 as a potent hCNT2 inhibitor (IC50 = 0.64 MUM), but further study was hampered due to its poor solubility. Here we describe the results of subsequent research to identify more soluble and more potent hCNT2 inhibitors, leading to the discovery of the benzimidazole nucleoside 22, which is the most potent hCNT2 inhibitor (IC50 = 0.062 MUM) reported to date. Compound 22 significantly suppressed the increase in plasma uric acid levels after oral administration of purine nucleosides in rats. Because compound 22 was poorly absorbed orally in rats (F = 0.51%), its pharmacologic action was mostly limited to the gastrointestinal tract. These findings suggest that inhibition of hCNT2 in the gastrointestinal tract can be a promising approach for the treatment of hyperuricemia. PMID- 27007872 TI - The implicit power motive predicts action selection. AB - Previous research has indicated that implicit motives can reliably predict which behaviors people select or decide to perform. However, so far, the question of how these motives are able to predict this action selection process has received little attention. Based on ideomotor theory, we argue that implicit motives can predict action selection when an action has become associated with a motive congruent (dis)incentive through repeated experiences with the action-outcome relationship. This idea was investigated by examining whether the implicit need for power (nPower) would come to predict action selection (i.e., choosing to press either of two buttons) when these actions had repeatedly resulted in motive congruent (dis)incentives (i.e., submissive or dominant faces). Both Studies 1 and 2 indicated that participants became more likely to select the action predictive of the motive-congruent outcome as their history with the action outcome relationship increased. Study 2 indicated that this effect stemmed from both an approach towards incentives and an avoidance of disincentives. These results indicate that implicit motives (particularly the power motive) can predict action selection as a result of learning which actions yield motive congruent (dis)incentives. Our findings therefore offer a model of how implicit motives can come to predict which behaviors people select to perform. PMID- 27007873 TI - Stretching the limits of knowledge attainable with live cell imaging in ARTs. PMID- 27007874 TI - Optimization of microelectrophoresis to select highly negatively charged sperm. AB - PURPOSE: The sperm membrane undergoes extensive surface remodeling as it matures in the epididymis. During this process, the sperm is encapsulated in an extensive glycocalyx layer, which provides the membrane with its characteristic negative electrostatic charge. In this study, we develop a method of microelectrophoresis and standardize the protocol to isolate sperm with high negative membrane charge. METHODS: Under an electric field, the percentage of positively charged sperm (PCS), negatively charged sperm (NCS), and neutrally charged sperm was determined for each ejaculate prior to and following density gradient centrifugation (DGC), and evaluated for sperm DNA damage, and histone retention. Subsequently, PCS, NCS, and neutrally charged sperm were selected using an ICSI needle and directly analyzed for DNA damage. RESULTS: When raw semen was analyzed using microelectrophoresis, 94 % were NCS. In contrast, DGC completely or partially stripped the negative membrane charge from sperm resulting PCS and neutrally charged sperm, while the charged sperm populations are increased with an increase in electrophoretic current. Following DGC, high sperm DNA damage and abnormal histone retention were inversely correlated with percentage NCS and directly correlated with percentage PCS. NCS exhibited significantly lower DNA damage when compared with control (P < 0.05) and PCS (P < 0.05). When the charged sperm population was corrected for neutrally charged sperm, sperm DNA damage was strongly associated with NCS at a lower electrophoretic current. CONCLUSION: The results suggest that selection of NCS at lower current may be an important biomarker to select healthy sperm for assisted reproductive treatment. PMID- 27007875 TI - Is oocyte donation a risk factor for preeclampsia? A systematic review and meta analysis. AB - PURPOSE: The objective of this meta-analysis is to determine whether there is a higher incidence of preeclampsia (PE) in pregnancies achieved by oocyte donation (OD) compared with pregnancies achieved by in vitro fertilization with autologous oocytes (IVF). METHODS: A systematic review was performed to identify relevant studies published from January 1994 until April 2015 with at least an abstract in English using PubMed, ISI Web of Knowledge, and clinicaltrials.gov. The 11 studies included in this systematic review were retrospective and prospective cohort studies of women reporting results on the association between oocyte donation vs. in vitro fertilization (exposure) and preeclampsia (outcome). RESULTS: Oocyte donation is a risk factor for the development of PE compared to IVF cycles, with a weighted OR of 3.12 under a fixed effects method (FEM: no heterogeneity between the studies). The weighted OR under a random effects model was 2.9 (REM: heterogeneity between the studies). The meta-regression analysis showed that neither multiple pregnancies (estimate = 0.08; p = 0.19) nor patient age (estimate = -2.29; p = 0.13) significantly explained the variability of the effect of oocyte donation on PE. Q statistic was 12.78 (p = 0.237), suggesting absence of heterogeneity between the studies. CONCLUSIONS: Pregnancies achieved by oocyte donation confer a threefold increase in the likelihood of developing PE than those achieved by in vitro fertilization with own oocytes. Physicians should be aware of this risk in order to both counsel patients and monitor pregnancies accordingly. PMID- 27007878 TI - Gyroscope like molecules consisting of trigonal or square planar osmium rotators within three-spoked dibridgehead diphosphine stators: syntheses, substitution reactions, structures, and dynamic properties. AB - Reactions of (NH4)2OsX6 (X = Cl, Br) with CO and the phosphines P((CH2)mCH[double bond, length as m-dash]CH2)3 (m = 6, a; 7, b; 8, c) give cis,cis,trans Os(CO)2(X)2(P((CH2)mCH[double bond, length as m-dash]CH2)3)2 (46-73%). These are treated with Grubbs' catalyst (7 mol%, 0.0010 M, C6H5Cl). Subsequent hydrogenations (PtO2) yield the gyroscope like complexes cis,cis,trans Os(CO)2(X)2(P((CH2)n)3P) (n = 2m + 2; X = Cl, 6a-c; Br, 7a-c ; 5-31%) and the isomers cis,cis,trans-Os(CO)2(X)2(P(CH2)n-1CH2)((CH2)n)(P(CH2)n-1CH2) (X = Cl, 6'ac; Br, 7'a-c;12-51%) derived from a combination of interligand and intraligand metatheses. Reductions of 6a,c, 6'b, and 7'b with C8K under CO atmospheres afford trans-Os(CO)3(P((CH2)n)3P) (9a,c, 79-82%) and trans Os(CO)3(P(CH2)15CH2)((CH2)16)(P(CH2)15CH2) (9'b, 53-84%). Reaction of 9a and CF3SO3H yields the cationic hydride complex mer,trans [Os(H)(CO)3(P((CH2)14)3P)](+) CF3SO3(-) (9a-H(+) CF3SO3(-); quantitative by NMR). Preparative reactions of 9a,c or 9'b and [H(OEt2)2](+) BArf(-) (BArf(-) = B(3,5 C6H3(CF3)2)4(-)) afford 9a,c-H(+) BArf(-) (80%) or 9'b-H(+) BArf(-) (68%). Reactions of 6a, 6'b, and 7a with MeLi or PhLi give cis,cis,trans Os(CO)2(Me)2(P((CH2)14)3P) (11a, 98%), cis,cis,trans Os(CO)2(Me)2(P(CH2)15CH2)((CH2)16)(P(CH2)15CH2) (98%), and cis,cis,trans Os(CO)2(Ph)2(P((CH2)14)3P) (12a, 58%). NMR data for 6a-c, 7a-c, 9a,c, 9a,c-H(+) X(-), and 11a indicate that rotation of the OsLy moieties is fast on the NMR time scale at room temperature. In contrast, the phenyl groups in 12a act as "brakes" and two sets of (13)C NMR signals are observed for the methylene chains (2 : 1). The crystal structures of 6a-c, 7b,c, 7'a, 9a, 9a -H(+) BArf(-), 11a, and 12a are analyzed with respect to OsLy rotation in solution and the solid state. PMID- 27007876 TI - Comparison of 2, 5, and 20 % O2 on the development of post-thaw human embryos. AB - PURPOSE: The objective of this study is to investigate the effect of 2, 5, and 20 % O2 on post-thaw day 3 human embryo culture until blastocyst stage. METHODS: One hundred fifty-five day 3 human embryos were used. One hundred twenty out of 155 embryos were recovered after thawing. Surviving embryos were distributed into 2, 5, or 20 % O2 groups and cultured for 2.5 days. At the end of culture, blastocyst formation was assessed, and then, embryos were collected for RT-qPCR or immunofluorescence analysis. RESULTS: Using visible blastocoel to define blastocyst formation, 58.7 % (27/46) of surviving day 3 embryos formed blastocyst at 2 % O2, 63.6 % (28/44) at 5 % O2, and 66.7 % (20/30) at 20 % O2. The difference in blastocyst formation rates was not significant. Average blastocyst cell number was 119.44 +/- 11.64 at 2 % O2, 142.55 +/- 22.47 at 5 % O2, and 97.29 +/- 14.87 at 20 % O2. Average apoptotic rate was 4.7 % +/- 0.4 % for blastocyst formed at 2 % O2, 3.5 % +/- 0.7 % at 5 % O2, and 5.8 % +/- 1.1 % at 20 % O2. Apoptosis rate was significantly lower for blastocysts formed at 5 % O2 (p < 0.05). Compared with gene expression levels at 5 % O2, which were arbitrarily set as "1," 20 % O2 is associated with significantly higher expression of BAX (2.14 +/- 0.47), G6PD (2.92 +/- 1.06), MnSOD (2.87 +/- 0.88), and HSP70.1 (8.68 +/- 4.19). For all genes tested, no significant differences were found between 2 and 5 % O2. CONCLUSION: The result suggests that development of cryopreserved human embryos from day 3 to blastocyst stage benefits from culture at 5 % O2. PMID- 27007877 TI - Anticancer Activity Studies of Ruthenium(II) Complex Toward Human Osteosarcoma HOS Cells. AB - A new Ru(II) complex [Ru(dmp)2(NMIP)](ClO4)2 (dmp = 2,9-dimethyl-1,10 phenanthroline, NMIP = 2'-(2"-nitro-3",4"-methylenedioxyphenyl)imidazo[4',5' f][1,10]-phenanthroline) was synthesized and characterized by elemental analysis, ESI-MS and (1)H NMR. The cytotoxic activity of the complex against MG-63, U2OS, HOS, and MC3T3-e1 cell lines was investigated by MTT method. The complex shows moderate cytotoxicity toward HOS (IC50 = 35.6 +/- 2.6 uM) and MC3T3-e1 (IC50 = 41.6 +/- 2.8 uM) cell lines. The morphological studies show that the complex can induce apoptosis in HOS cells and cause an increase of reactive oxygen species levels and a decrease in the mitochondrial membrane potential. The cell cycle distribution demonstrates that the complex inhibits the cell growth at S phase. Additionally, the antitumor activity in vivo reveals that the complex can induce a decrease in tumor weight. PMID- 27007879 TI - Recombinant canarypox virus expressing the VP2 protein of infectious bursal disease virus induces protection in vaccinated SPF chickens. PMID- 27007880 TI - Stability of HIV-1 subtype B and C Tat is associated with variation in the carboxyl-terminal region. AB - The multifunctional trans-activator Tat is an essential regulatory protein for HIV-1 replication and is characterized by high sequence diversity. Numerous experimental studies have examined Tat in HIV-1 subtype B, but research on subtype C Tat is lacking, despite the high prevalence of infections caused by subtype C worldwide. We hypothesized that amino acid differences contribute to functional differences among Tat proteins. In the present study, we found that subtype B NL4-3 Tat and subtype C isolate HIV1084i Tat exhibited differences in stability by overexpressing the fusion protein Tat-Flag. In addition, 1084i Tat can activate LTR and NF-kappaB more efficiently than NL4-3 Tat. In analyses of the activities of the truncated forms of Tat, we found that the carboxyl-terminal region of Tat regulates its stability and transactivity. According to our results, we speculated that the differences in stability between B-Tat and C-Tat result in differences in transactivation ability. PMID- 27007882 TI - The USMLE Step 2 CS: Time for a change. AB - The United States Medical Licensing Examination (USMLE((r))) Steps are a series of mandatory licensing assessments for all allopathic (MD degree) medical students in their transition from student to intern to resident physician. Steps 1, 2 Clinical Knowledge (CK), and 3 are daylong multiple-choice exams that quantify a medical student's basic science and clinical knowledge as well as their application of that knowledge using a three-digit score. In doing so, these Steps provide a standardized assessment that residency programs use to differentiate applicants and evaluate their competitiveness. Step 2 Clinical Skills (CS), the only other Step exam and the second component of Step 2, was created in 2004 to test clinical reasoning and patient-centered skills. As a Pass/Fail exam without a numerical scoring component, Step 2 CS provides minimal differentiation among applicants for residency programs. In this personal view article, it is argued that the current Step 2 CS exam should be eliminated for US medical students and propose an alternative consistent with the mission and purpose of the exam that imposes less of a burden on medical students. PMID- 27007881 TI - A Nanoparticle Platform To Evaluate Bioconjugation and Receptor-Mediated Cell Uptake Using Cross-Linked Polyion Complex Micelles Bearing Antibody Fragments. AB - Targeted nanomedicines are a promising technology for treatment of disease; however, preparation and characterization of well-defined protein-nanoparticle systems remain challenging. Here, we describe a platform technology to prepare antibody binding fragment (Fab)-bearing nanoparticles and an accompanying real time cell-based assay to determine their cellular uptake compared to monoclonal antibodies (mAbs) and Fabs. The nanoparticle platform was composed of core-cross linked polyion complex (PIC) micelles prepared from azide-functionalized PEG-b poly(amino acids), that is, azido-PEG-b-poly(l-lysine) [N3-PEG-b-PLL] and azido PEG-b-poly(aspartic acid) [N3-PEG-b-PAsp]. These PIC micelles were 30 nm in size and contained approximately 10 polymers per construct. Fabs were derived from an antibody binding the EphA2 receptor expressed on cancer cells and further engineered to contain a reactive cysteine for site-specific attachment and a cleavable His tag for purification from cell culture expression systems. Azide functionalized micelles and thiol-containing Fab were linked using a heterobifunctional cross-linker (FPM-PEG4-DBCO) that contained a fluorophenyl maleimide for stable conjugation to Fabs thiols and a strained alkyne (DBCO) group for coupling to micelle azide groups. Analysis of Fab-PIC micelle conjugates by fluorescence correlation spectroscopy, size exclusion chromatography, and UV-vis absorbance determined that each nanoparticle contained 2-3 Fabs. Evaluation of cellular uptake in receptor positive cancer cells by real time fluorescence microscopy revealed that targeted Fab-PIC micelles achieved higher cell uptake than mAbs and Fabs, demonstrating the utility of this approach to identify targeted nanoparticle constructs with unique cellular internalization properties. PMID- 27007883 TI - Synthesis of Diagnostic Silicon Nanoparticles for Targeted Delivery of Thiourea to Epidermal Growth Factor Receptor-Expressing Cancer Cells. AB - The novel thiourea-functionalized silicon nanoparticles (SiNPs) have been successfully synthesized using allylamine and sulforaphane, an important anticancer drug, followed by a hydrosilylation reaction on the surface of hydrogen terminated SiNPs. Their physiochemical properties have been investigated by photoluminescence emission, Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay has been employed to evaluate in vitro toxicity in human colorectal adenocarcinoma (Caco-2) cells and human normal colon epithelial (CCD) cells. The results show significant toxicity of thiourea SiNPs after 72 h of incubation in the cancer cell line, and the toxicity is concentration dependent and saturated for concentrations above 100 MUg/mL. Confocal microscopy images have demonstrated the internalization of thiourea-functionalized SiNPs inside the cells. Flow cytometry data has confirmed receptor-mediated targeting in cancer cells. This nanocomposite takes advantage of the epidermal growth factor receptor (EGFR) active targeting of the ligand in addition to the photoluminescence properties of SiNPs for bioimaging purposes. The results suggest that this novel nanosystem can be extrapolated for active targeting of the receptors that are overexpressed in cancer cells such as EGFR using the targeting characteristics of thiourea-functionalized SiNPs and therefore encourage further investigation and development of anticancer agents specifically exploiting the EGFR inhibitory activity of such nanoparticles. PMID- 27007884 TI - Surgical strategies and novel alternatives for the closure of ventricular septal defects. AB - A variety of therapies are available to close ventricular septal defects (VSDs). These include surgical closure on bypass, percutaneous device closure, as well as perventricular hybrid closure. Due to the incidence of heart block (1-5%) associated with percutaneous device closure of perimembranous VSDs, surgical closure presently remains the gold standard and preferred therapy for these defects. Therapeutic options are more varied for muscular VSDs. Beyond infancy, transcatheter closure offers excellent results with low morbidity and mortality, without the need for cardiopulmonary bypass. Infants however have a higher incidence of adverse events using a percutaneous approach. Large mid-muscular VSDs in infants can be treated successfully using a hybrid approach, surgical closure on bypass or a percutaneous approach. However, VSDs located apically or anteriorly are difficult to identify surgically and for these infants, perventricular hybrid closure should be considered as the preferred therapeutic modality. However, some VSD's also can be closed percutaneously. PMID- 27007885 TI - Glucocorticoid effects on angiogenesis are associated with mTOR pathway activity. AB - Glucocorticoids (GC) often are administered during pregnancy, but despite their widespread use in clinical practice, it remains uncertain how GC exposure affects pro-angiogenic factors and their receptors. We investigated the effects of GC on vascular endothelial growth factor (VEGF), placental growth factor (PIGF), vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) protein and mRNA expressions and investigated the possible association of GC with the Akt/mTOR pathway. We incubated human umbilical vein endothelial cells (HUVECs) with a synthetic GC, triamcinolone acetonide (TA). TA administration caused decreased cellular and soluble VEGF and VEGFR1 protein expressions and increased soluble VEGFR2 expression. VEGF, VEGFR1 and VEGFR2 mRNA expressions were altered in a time and dose dependent manner. PIGF protein expression was unaffected by TA treatment, but PIGF mRNA expression decreased in a dose dependent manner after incubation for 48 and 72 h. Phospho mTOR and phospho-Akt expressions were unaffected. Phospho-p70S6K and phospho 4EBP1 protein expressions and the vascular network forming capacity of HUVECs decreased in a dose dependent manner. We found that GC exert detrimental effects on angiogenesis by altering cellular and soluble angiogenic protein and mRNA levels, and vascular network forming capacities by the Akt/mTOR pathway. PMID- 27007886 TI - Preoperative Differential Diagnosis of Canine Adrenal Tumors Using Triple-Phase Helical Computed Tomography. AB - OBJECTIVE: To characterize the computed tomography (CT) findings for canine adrenal tumors, including cortical adenoma, cortical adenocarcinoma, and pheochromocytoma, and to evaluate the feasibility and usefulness of preoperative triple-phase helical CT for differentiation of tumor types and surgical planning. STUDY DESIGN: Retrospective study. ANIMALS: Dogs with adrenal tumors (n=36). METHODS: All dogs underwent triple-phase helical CT, followed by adrenalectomy and histopathological diagnosis of the resected mass. Precontrast images, arterial, venous, and delayed phase images were obtained. In all cases, morphological characteristics and CT values and calculations, including the percentage enhancement washout ratio, relative percentage washout, enhancement washin, and enhancement washout, were analyzed and compared among the tumor types. RESULTS: Of the 36 dogs with adrenal masses, cortical adenocarcinoma was most commonly diagnosed (16 dogs), followed by pheochromocytoma (13 dogs), and cortical adenoma (7 dogs). The precontrast minimum CT value and enhancement washout between venous and delayed phases in the cortical adenoma were significantly higher than those in the cortical adenocarcinoma. The maximum CT values of the precontrast image and arterial and venous phases, the enhancement washin and washouts, percentage enhancement washout ratio, and relative percentage washout in the pheochromocytomas were significantly higher than those in cortical adenocarcinoma. CONCLUSION: The differential diagnosis of canine adrenal tumors was feasible based on triple-phase CT findings, including morphological features, CT values, and intratumoral contrast attenuation. Preoperative diagnosis using triple-phase helical CT may be useful for surgical planning in dogs with adrenal tumors. PMID- 27007887 TI - Understanding physical activity in the group home setting: a qualitative inquiry. AB - PURPOSE: Persons with intellectual disabilities have low physical activity levels and high rates of chronic disease. One predictor limitedly explored is the home environment, which could influence the type and amount of physical activity in this population. The purpose of this study is to qualitatively explore physical activity in the group home setting and determine what key stakeholders want from a physical activity programme. METHOD: This study adopted a qualitative descriptive design, using semistructured focus groups. Twenty stakeholders (i.e., residents with intellectual disability, support staff and programme coordinators) participated in one of three focus groups, separated by stakeholder status. RESULTS: A number of factors emerged that would assist rehabilitation professionals in understanding physical activity within the group home setting. The following six meta-themes were identified: nature of residents' physical activity, facilitators to physical activity, barriers to physical activity, personal factors, organizational factors and solutions to increase physical activity. CONCLUSIONS: Findings suggest that residents with intellectual disabilities have low physical activity and opportunities for participation. Key attributes of the group home setting were identified between barriers and facilitators to activity. Consideration for the development of physical activity programmes should focus on the unique needs of the group home setting as expressed by stakeholders. Implications for rehabilitation Physical activity can improve physical fitness, function, and community participation yet physical activity remains low among adults with intellectual disabilities. Understanding physical activity within the group home setting is essential to develop targeted interventions to increase activity within that environment. Key barriers for physical activity within the group home setting include; operational priorities, limited staff, staff turnover, busy schedules, and staff attitudes towards physical activity. PMID- 27007888 TI - Stretchable, High-k Dielectric Elastomers through Liquid-Metal Inclusions. AB - An all-soft-matter composite with exceptional electro-elasto properties is demonstrated by embedding liquid-metal inclusions in an elastomer matrix. This material exhibits a unique combination of high dielectric constant, low stiffness, and large strain limit (ca. 600% strain). The elasticity, electrostatics, and electromechanical coupling of the composite are investigated, and strong agreement with predictions from effective medium theory is found. PMID- 27007889 TI - Molecular Detection of Streptococcus pneumoniae on Dried Blood Spots from Febrile Nigerian Children Compared to Culture. AB - BACKGROUND: Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture. METHODS: Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples. RESULTS: A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4-90.1%) and 62.5% (95% CI 24.5-91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture. CONCLUSIONS: Rt PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens. PMID- 27007890 TI - Reduced Breastfeeding Rates in Firstborn Late Preterm and Early Term Infants. AB - OBJECTIVES: The primary objective was to determine the rate of breastfeeding by gestational age reported by new mothers 1 month postpartum, with particular focus on early term newborns (37-38(6)/7 weeks). MATERIALS AND METHODS: Three thousand six primiparous women aged 18-36 years were interviewed during their third trimester and again 1 month postpartum. Logistic regression analysis was used to model the association between gestational age and breastfeeding 1 month postpartum among those who reported that they planned to breastfeed, controlling for potentially confounding variables. RESULTS: Two thousand seven hundred seventy-two women planned to breastfeed (92.2%), among whom 116 (4.2%) delivered late preterm (34-36(6)/7 weeks), 519 (18.7%) early term (37-38(6)/7 weeks), and 2,137 (77.1%) term or postterm (39+ weeks). Among those who delivered late preterm, 63.8% were breastfeeding 1 month postpartum, early term 72.6%, and term or postterm 76.5%. This relationship was verified by a multivariate logistic regression analysis; late preterm newborns were significantly less likely to be breastfeeding 1 month postpartum than the term or postterm newborns (odds ratio [OR] 0.44; 95% confidence interval [CI] 0.28-0.69; p <= 0.0001), as were early term newborns (OR 0.77; 95% CI 0.60-0.99; p = 0.038). CONCLUSIONS: In this large prospective study of first-time mothers and newborns, gestational age was significantly associated with breastfeeding 1 month postpartum; highlighting late preterm and early term infants as populations at risk for shortened breastfeeding duration and the need to create specific breastfeeding support and education. PMID- 27007891 TI - Antioxidant responses of wheat plants under stress. AB - Currently, food security depends on the increased production of cereals such as wheat (Triticum aestivum L.), which is an important source of calories and protein for humans. However, cells of the crop have suffered from the accumulation of reactive oxygen species (ROS), which can cause severe oxidative damage to the plants, due to environmental stresses. ROS are toxic molecules found in various subcellular compartments. The equilibrium between the production and detoxification of ROS is sustained by enzymatic and nonenzymatic antioxidants. In the present review, we offer a brief summary of antioxidant defense and hydrogen peroxide (H2O2) signaling in wheat plants. Wheat plants increase antioxidant defense mechanisms under abiotic stresses, such as drought, cold, heat, salinity and UV-B radiation, to alleviate oxidative damage. Moreover, H2O2 signaling is an important factor contributing to stress tolerance in cereals. PMID- 27007892 TI - The complex translocation (9;14;14) involving IGH and CEBPE genes suggests a new subgroup in B-lineage acute lymphoblastic leukemia. AB - Many subtypes of acute lymphoblastic leukemia (ALL) are associated with specific chromosomal rearrangements. The complex translocation t(9;14;14), a variant of the translocation (14;14)(q11;q32), is a rare but recurrent chromosomal abnormality involving the immunoglobulin heavy-chain (IGH) and CCAAT enhancer binding protein (CEBPE) genes in B-lineage ALL (B-ALL) and may represent a new B ALL subgroup. We report here the case of a 5-year-old girl with B-ALL, positive for CD19, CD38 and HLA-DR. A direct technique and G-banding were used for chromosomal analysis and fluorescentin situ hybridization (FISH) with BAC probes was used to investigate a possible rearrangement of the IGH andCEBPE genes. The karyotype exhibit the chromosomal aberration 46,XX,del(9)(p21),t(14;14)(q11;q32). FISH with dual-color break-apartIGH-specific and CEPBE-specific bacterial artificial chromosome (BAC) probes showed a complex t(9;14;14) associated with a deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) and paired box gene 5 (PAX5) at 9p21-13 and duplication of the fusion gene IGH-CEBPE. PMID- 27007893 TI - Genotypic diversity of the Killer Cell Immunoglobulin-like Receptors (KIR) and their HLA class I Ligands in a Saudi population. AB - Killer Cell Immunoglobulin-like Receptors (KIR) have been used as good markers for the study of genetic predisposition in many diseases and in human genetic population dynamics. In this context, we have investigated the genetic diversity of KIR genes and their main HLA class I ligands in Saudi population and compared the data with other studies of neighboring populations. One hundred and fourteen randomly selected healthy Saudi subjects were genotyped for the presence or absence of 16 KIR genes and their HLA-C1, -C2, -Bw4Thr80 and Bw4Ile80 groups, using a PCR-SSP technique. The results show the occurrence of the framework genes (3DL2, 3DL3 and 2DL4) and the pseudogenes (2DP1 and 3DP1) at highest frequencies. All inhibitory KIR (iKIR) genes appeared at higher frequencies than activating genes (aKIR), except for 2DS4 with a frequency of 90.35%. A total of 55 different genotypes were observed appearing at different frequencies, where 12 are considered novel. Two haplotypes were characterized, AA and Bx (BB and AB), which were observed in 24.5% and 75.5% respectively of the studied group. The frequencies of iKIR + HLA associations were found to be much higher than aKIR + HLA. KIR genes frequencies in the Saudi population are comparable with other Middle Eastern and North African populations. PMID- 27007894 TI - Lack of detection of human papillomavirus DNA in prostate carcinomas in patients from northeastern Brazil. AB - Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied. PMID- 27007895 TI - The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease. AB - The clinical utility of serum ferritin as a biomarker of disease severity and prognosis in Gaucher disease (GD) is still debated. Here, we aimed to evaluate ferritin and its relation to clinicolaboratory parameters of GD patients seen at the Reference Center for Gaucher Disease of Rio Grande do Sul, Brazil, so as to gather evidence on the utility of ferritin as a biomarker of this condition. A retrospective chart review was performed collecting pre-and posttreatment data from GD patients. Eighteen patients with ferritin levels available before and after treatment were included in the study. Nine of these participants were males, and seventeen had type I GD. All patients were given either enzyme replacement (n = 16) or substrate reduction therapy (n = 2), and ferritin was found to decrease from 756 [318-1441] ng/mL at baseline to 521 [227-626] ng/mL (p=0.025) after 28.8 month soft treatment. Serum ferritin levels did not correlate with measures of disease severity, but showed an association with age at onset of treatment (rho= 0.880; n = 18; p < 0.001). In conclusion, although serum ferritin did not correlate with disease severity, after a median 28.8 months of treatment, clinical outcomes had clearly improved, and ferritin levels had decreased. PMID- 27007896 TI - Tetrasomy 3q26.32-q29 due to a supernumerary marker chromosome in a child with pigmentary mosaicism of Ito. AB - Pigmentary mosaicism of Ito (PMI) is a skin abnormality often characterized by hypopigmentation of skin, following, in most cases, the Blaschko lines, usually associated with extracutaneous abnormalities, especially abnormalities of the central nervous system (CNS). It is suggested that this pattern arises from the presence and migration of two cell lineages in the ectoderm layer during the embryonic period and embryonic cell migration, with different gene expression profiles associated with pigmentation. Several types of chromosomal aberrations, with or without mosaicism, have been associated with this disorder. This study comprised clinical description and cytogenetic analysis of a child with PMI. The G-banded karyotype analysis revealed a supernumerary marker chromosome in 76% of the analyzed metaphases from peripheral blood lymphocytes. Array genomic hybridization analysis showed a copy number gain between 3q26.32-3q29, of approximately 20.5 Mb. Karyotype was defined as 47,XX,+mar[38]/46,XX[12].arr 3q26.32-3q29(177,682,859- 198,043,720)x4 dn. Genes mapped in the overlapping region among this patient and three other cases described prior to this study were listed and their possible involvement on PMI pathogenesis is discussed. PMID- 27007897 TI - Cytogenetic variation of repetitive DNA elements in Hoplias malabaricus (Characiformes - Erythrinidae) from white, black and clear water rivers of the Amazon basin. AB - Hoplias malabaricus is a common fish species occurring in white, black and clear water rivers of the Amazon basin. Its large distribution across distinct aquatic environments can pose stressful conditions for dispersal and creates possibilities for the emergence of local adaptive profiles. We investigated the chromosomal localization of repetitive DNA markers (constitutive heterochromatin, rDNA and the transposable element REX-3) in populations from the Amazonas river (white water), the Negro river (black water) and the Tapajos river (clear water), in order to address the variation/association of cytogenomic features and environmental conditions. We found a conserved karyotypic macrostructure with a diploid number of 40 chromosomes (20 metacentrics + 20 submetacentrics) in all the samples. Heteromorphism in pair 14 was detected as evidence for the initial differentiation of an XX/XY system. Minor differences detected in the amount of repetitive DNA markers are interpreted as possible signatures of local adaptations to distinct aquatic environments. PMID- 27007898 TI - Genetic analysis reveals candidate species in the Scinax catharinae clade (Amphibia: Anura) from Central Brazil. AB - Scinax (Anura: Hylidae) is a species-rich genus of amphibians (113 spp.), divided into five species groups by morphological features. Cladistic analyses however revealed only two monophyletic clades in these groups: Scinax catharinae and Scinax ruber. Most species from the S. catharinae clade are found in Atlantic rainforest, except for Scinax canastrensis,S. centralis, S. luizotavioi, S. machadoi,S. pombali and S. skaios. In the present work, specimens of Scinax collected in Chapada dos Guimaraes, central Brazil, were morphologically compatible with species from theS. catharinae group. On the other hand, genetic analysis based on mitochondrial (16S and 12S) and nuclear (rhodopsin) sequences revealed a nucleotide divergence of 6 to 20% between Scinax sp. and other congeners from the Brazilian savannah (Cerrado). Accordingly, Bayesian inference placed Scinax sp. in the S. catharinae clade with high support values. Hence, these findings strongly indicate the presence of a new species in the S. catharinae clade from the southwestern portion of the Brazilian savannah. To be properly validated as a novel species, detailed comparative morphological and bioacustic studies with other taxa from Brazil such asS. canastrensis, S. centralis, S. luizotavioi, S. machadoi, S. pombali and S. skaios are required. PMID- 27007899 TI - Genetic analysis of reciprocal differences in the inheritance of in vitro characters in pearl millet. AB - Reciprocal differences persist in nature because of the unequal contribution of cytoplasmic determinants from male and female gametes to the zygote. The inheritance of genetic differences is an important factor that influences various traits, including somatic embryogenesis and regeneration in vitro. In this report, we estimate the cytoplasmic and maternal effects in pearl millet and their adequacy in describing the observed reciprocal differences based on an in depth study of the parents, F2s and reciprocal backcross progenies needed for fitting genetical models. Our study revealed that of the two characters examined, embryogenic callus quantity and regeneration frequency, the former showed a greater proportion of cytoplasmic nuclear interaction whereas the latter showed a greater role of nuclear factors. Additive-maternal effects influenced total callus quantity and dominance-maternal effects influenced total callus quantity, embryogenic callus quantity and regeneration frequency. Dwarfing was associated with the production of large quantities of embryogenic callus that had visually recognizable characteristics. The phenotypic nature of dwarf parents (green dwarf with long narrow leaves) with a genetic basis for a given character controlled by nuclear and cytoplasmic determinants can be exploited for other breeding programs. PMID- 27007900 TI - The PIN1 family gene PvPIN1 is involved in auxin-dependent root emergence and tillering in switchgrass. AB - Switchgrass (Panicum virgatum L.; family Poaceae) is a warm-season C4 perennial grass. Tillering plays an important role in determining the morphology of aboveground parts and the final biomass yield of switchgrass. Auxin distribution in plants can affect a variety of important growth and developmental processes, including the regulation of shoot and root branching, plant resistance and biological yield. Auxin transport and gradients in plants are mediated by influx and efflux carriers. PvPIN1, a switchgrass PIN1-like gene that is involved in regulating polar transport, is a putative auxin efflux carrier. Neighbor-joining analysis using sequences deposited in NCBI databases showed that the PvPIN1gene belongs to the PIN1 family and is evolutionarily closer to the Oryza sativa japonica group. Tiller emergence and development was significantly promoted in plants subjected toPvPIN1 RNA interference (RNAi), which yielded a phenotype similar to that of wild-type plants treated with the auxin transport inhibitor TIBA (2,3,5-triiodobenzoic acid). A transgenic approach that inducedPvPIN1 gene overexpression or suppression altered tiller number and the shoot/root ratio. These data suggest that PvPIN1plays an important role in auxin-dependent adventitious root emergence and tillering. PMID- 27007901 TI - Identification and characterization of MAGO and Y14 genes in Hevea brasiliensis. AB - Mago nashi (MAGO) and Y14 proteins are highly conserved among eukaryotes. In this study, we identified two MAGO (designated as HbMAGO1 andHbMAGO2) and two Y14 (designated as HbY14aand HbY14b) genes in the rubber tree (Hevea brasiliensis) genome annotation. Multiple amino acid sequence alignments predicted that HbMAGO and HbY14 proteins are structurally similar to homologous proteins from other species. Tissue-specific expression profiles showed that HbMAGO and HbY14 genes were expressed in at least one of the tissues (bark, flower, latex, leaf and root) examined. HbMAGOs and HbY14s were predominately located in the nucleus and were found to interact in yeast two-hybrid analysis (YTH) and bimolecular fluorescence complementation (BiFC) assays. HbMAGOs and HbY14s showed the highest transcription in latex and were regulated by ethylene and jasmonate. Interaction between HbMAGO2 and gp91phox (a large subunit of nicotinamide adenine dinucleotide phosphate) was identified using YTH and BiFC assays. These findings suggested that HbMAGO may be involved in the aggregation of rubber particles in H. brasiliensis. PMID- 27007902 TI - Assessment of genetic diversity in Brazilian barley using SSR markers. AB - Barley is a major cereal grown widely and used in several food products, beverage production and animal fodder. Genetic diversity is a key component in breeding programs. We have analyzed the genetic diversity of barley accessions using microsatellite markers. The accessions were composed of wild and domesticated barley representing genotypes from six countries and three breeding programs in Brazil. A total of 280 alleles were detected, 36 unique to Brazilian barley. The marker Bmag120 showed the greatest polymorphism information content (PIC), with the highest mean value found on chromosome three, and the lowest on chromosomes four and six. The wild accessions presented the highest diversity followed by the foreign genotypes. Genetic analysis was performed using Principal Coordinates Analysis, UPGMA clustering, and Bayesian clustering analysis implemented in Structure. All results obtained by the different methods were similar. Loss of genetic diversity has occurred in Brazilian genotypes. The number of alleles detected in genotypes released in 1980s was higher, whereas most of the cultivars released thereafter showed lower PIC and clustered in separate subgroups from the older cultivars. The use of a more diverse panel of genotypes should be considered in order to exploit novel alleles in Brazilian barley breeding programs. PMID- 27007903 TI - Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits. AB - The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID- 27007904 TI - Functional abilities of cultivable plant growth promoting bacteria associated with wheat (Triticum aestivum L.) crops. AB - In the pursuit of sustainable agriculture, bioinoculants usage as providers of a crop's needs is a method to limit environmental damage. In this study, a collection of cultivable putative plant growth promoting (PGP) bacteria associated with wheat crops was obtained and this bacterial sample was characterized in relation to the functional diversity of certain PGP features. The isolates were obtained through classical cultivation methods, identified by partial 16S rRNA gene sequencing and characterized for PGP traits of interest. Functional diversity characterization was performed using Categorical Principal Component Analysis (CatPCA) and Multiple Correspondence Analysis (MCA). The most abundant genera found among the 346 isolates were Pseudomonas, Burkholderia, and Enterobacter. Occurrence of PGP traits was affected by genus, niche, and sampling site. A large number of genera grouped together with the ability to produce indolic compounds; phosphate solubilization and siderophores production formed a second group related to fewer genera, in which the genus Burkholderia has a great importance. The results obtained may help future studies aiming prospection of putative plant growth promoting bacteria regarding the desired organism and PGP trait. PMID- 27007905 TI - Protective effects of acerola juice on genotoxicity induced by iron in vivo. AB - Metal ions such as iron can induce DNA damage by inducing reactive oxygen species (ROS) and oxidative stress. Vitamin C is one of the most widely consumed antioxidants worldwide, present in many fruits and vegetables, especially inMalpighia glabra L., popularly known as acerola, native to Brazil. Acerola is considered a functional fruit due to its high antioxidant properties and phenolic contents, and therefore is consumed to prevent diseases or as adjuvant in treatment strategies. Here, the influence of ripe and unripe acerola juices on iron genotoxicity was analyzed in vivo using the comet assay and micronucleus test. The comet assay results showed that acerola juice exerted no genotoxic or antigenotoxic activity. Neither ripe nor unripe acerola juices were mutagenic to animals treated with juices, in micronucleus test. However, when compared to iron group, the pre-treatment with acerola juices exerted antimutagenic activity, decreasing significantly micronucleus mean values in bone marrow. Stage of ripeness did not influence the interaction of acerola compounds with DNA, and both ripe and unripe acerola juices exerted protective effect over DNA damage generated by iron. PMID- 27007906 TI - Human mesenchymal stem cells are resistant to cytotoxic and genotoxic effects of cisplatin in vitro. AB - Mesenchymal stem cells (MSCs) are known for their important properties involving multilineage differentiation potential., trophic factor secretion and localization along various organs and tissues. On the dark side, MSCs play a distinguished role in tumor microenvironments by differentiating into tumor associated fibroblasts or supporting tumor growth via distinct mechanisms. Cisplatin (CIS) is a drug widely applied in the treatment of a large number of cancers and is known for its cytotoxic and genotoxic effects, both in vitro and in vivo. Here we assessed the effects of CIS on MSCs and the ovarian cancer cell line OVCAR-3, by MTT and comet assays. Our results demonstrated the resistance of MSCs to cell death and DNA damage induction by CIS, which was not observed when OVCAR-3 cells were exposed to this drug. PMID- 27007907 TI - Multiple introductions and gene flow in subtropical South American populations of the fireweed, Senecio madagascariensis(Asteraceae). AB - Non-indigenous plants exhibit different attributes that make them aggressive competitors with indigenous plants and serious threats to biodiversity.Senecio madagascariensis (fireweed, Asteraceae), a native from southern Africa, is a strong competitor in agricultural activities and has toxic alkaloids that may result in high cattle mortality. In Brazil, this weed was collected for the first time in 1995 and has since spread quickly throughout the Pampas region. To better understand the invasion of the fireweed in South America, we used a genetic characterization with internal transcribed spacer (ITS) and microsatellite markers. Based on the ITS data, the southern Brazil populations of S. madagascariensis shared genetic homology with samples taken from the Hawaiian Islands and South Africa. Microsatellite analysis showed the genetic diversity split in two clusters, perhaps intimating the independent introduction of each species into South America. Although fireweed was introduced recently in southern Brazil, the considerable levels of genetic diversity, gene flow, and inbreeding may indicate success in the species establishment in this environment. PMID- 27007908 TI - Unraveling the evolutionary scenario of the hobo element in populations of Drosophila melanogaster and D. simulans in South America using the TPE repeats as markers. AB - Transposable elements (TEs) are nucleotide sequences found in most studied genomes. These elements are highly diversified and have a large variation in nucleotide structure and mechanisms of transposition. hobo is a member of class II, belonging to hAT superfamily, described inDrosophila melanogaster, and it presents in its Open Reading Frame, a repetitive region encoding the amino acids threonine-proline-glutamic acid (TPE), which shows variability in the number of repeats in some regions of the world. Due to this variability some evolutionary scenarios of the hobo element are discussed, such as the scenario of the invasion of hobo element in populations ofD. melanogaster. In the present study, we investigated 22 DNA sequences of D. melanogaster and seven sequences ofD. simulans, both from South America, to check the number of repetitions of TPE, in order to clarify the evolutionary scenario of thehobo element in these populations. Our results showed a monomorphism in populations of both species in South America, with only three TPE repeats. Hence, we discuss and propose an evolutionary scenario of the invasion of the hobo element in populations of D. melanogaster and D. simulans. PMID- 27007909 TI - Six1 induces protein synthesis signaling expression in duck myoblasts mainly via up-regulation of mTOR. AB - As a critical transcription factor, Six1 plays an important role in the regulation of myogenesis and muscle development. However, little is known about its regulatory mechanism associated with muscular protein synthesis. The objective of this study was to investigate the effects of overexpression ofSix1 on the expression of key protein metabolism-related genes in duck myoblasts. Through an experimental model where duck myoblasts were transfected with a pEGFP duSix1 construct, we found that overexpression of duckSix1 could enhance cell proliferation activity and increase mRNA expression levels of key genes involved in the PI3K/Akt/mTOR signaling pathway, while the expression of FOXO1, MuRF1and MAFbx was not significantly altered, indicating thatSix1 could promote protein synthesis in myoblasts through up-regulating the expression of several related genes. Additionally, in duck myoblasts treated with LY294002 and rapamycin, the specific inhibitors ofPI3K and mTOR, respectively, the overexpression of Six1 could significantly ameliorate inhibitive effects of these inhibitors on protein synthesis. Especially, the mRNA expression levels of mTOR and S6K1 were observed to undergo a visible change, and a significant increase in protein expression of S6K1 was seen. These data suggested that Six1plays an important role in protein synthesis, which may be mainly due to activation of the mTOR signaling pathway. PMID- 27007910 TI - How comparative psychology can shed light on human evolution: Response to Beran et al.'s discussion of "Cognitive capacities for cooking in chimpanzees". AB - We recently reported a study (Warneken & Rosati Proceedings of the Royal Society B, 282, 20150229, 2015) examining whether chimpanzees possess several cognitive capacities that are critical to engage in cooking. In a subsequent commentary, Beran, Hopper, de Waal, Sayers, and Brosnan Learning & Behavior (2015) asserted that our paper has several flaws. Their commentary (1) critiques some aspects of our methodology and argues that our work does not constitute evidence that chimpanzees can actually cook; (2) claims that these results are old news, as previous work had already demonstrated that chimpanzees possess most or all of these capacities; and, finally, (3) argues that comparative psychological studies of chimpanzees cannot adequately address questions about human evolution, anyway. However, their critique of the premise of our study simply reiterates several points we made in the original paper. To quote ourselves: "As chimpanzees neither control fire nor cook food in their natural behavior, these experiments therefore focus not on whether chimpanzees can actually cook food, but rather whether they can apply their cognitive skills to novel problems that emulate cooking" (Warneken & Rosati Proceedings of the Royal Society B, 282, 20150229, 2015, p. 2). Furthermore, the methodological issues they raise are standard points about psychological research with animals-many of which were addressed synthetically across our 9 experiments, or else are orthogonal to our claims. Finally, we argue that comparative studies of extant apes (and other nonhuman species) are a powerful and indispensable method for understanding human cognitive evolution. PMID- 27007911 TI - Catalpol reduces the production of inflammatory mediators via PPAR-gamma activation in human intestinal Caco-2 cells. AB - Catalpol, a major iridoid glycoside present in Rehmannia glutinosa, has been reported to show a variety of pharmacological properties. However, the molecular mechanism underlying the anti-inflammatory effect of catalpol in intestinal cells remains poorly understood. The present study was aimed at investigating the effects of catalpol on the production of inflammatory mediators and its underlying signaling pathways in human intestinal Caco-2 cells. Catalpol significantly inhibited IL-1beta-induced mRNA synthesis and protein production of pro-inflammatory cytokines, including IL-6, IL-8, and MCP-1. Further investigation of the molecular mechanism revealed that the anti-inflammatory effect of catalpol in Caco-2 cells is similar to that of troglitazone-a synthetic peroxisome proliferator-activated receptor (PPAR)-gamma agonist-on intestinal inflammation mediated by PPAR-gamma activation. These findings suggest that the clinical application of medicinal plants that contain catalpol may lead to a partial prevention of intestinal inflammation. PMID- 27007912 TI - Impact of Clothing on Dermal Exposure to Phthalates: Observations and Insights from Sampling Both Skin and Clothing. AB - Clothing can either retard or accelerate dermal exposure to phthalates. To investigate the impact of clothing on dermal exposure to six phthalates (DMP/DEP/DiBP/DnBP/BBzP/DEHP) in real environments, two sets of experiments have been conducted: (1) Skin wipes were collected from 11 adults to examine the phthalate levels on both bare-skin (hand/forehead) and clothing-covered body locations (arm/back/calf); (2) Five adults were asked to wear just-washed jeans for 1 day (1(st) experiment), 5 days (2(nd) experiment), and 10 days (3(rd) experiment). Phthalate levels on their legs were measured on selected days during the wearing period, and phthalate levels in the jeans were measured at the end of each experiment and again after washing. Measured phthalate levels on body locations covered by clothing were lower than those on uncovered locations, but still substantial. Dermal uptake would be underestimated by a factor of 2 to 5 if absorption through body locations covered by clothing were neglected. Phthalate levels in the jeans and on the legs increased with the wearing time. However, the levels in the jeans and on the legs were not strongly correlated, indicating that other pathways, e.g, contact with bedding or bedclothes, likely contribute to the levels on the legs. The efficiency with which laundering washing removed phthalates from the jeans increased with decreasing Kow; median values ranged from very low (<5%) for DEHP to very high (~75%) for DMP. PMID- 27007913 TI - Immunostimulating and Gram-negative-specific antibacterial cyclotides from the butterfly pea (Clitoria ternatea). AB - Cyclotides are plant-derived, cyclic miniproteins with three interlocking disulfide bonds that have attracted great interests because of their excellent stability and potential as peptide therapeutics. In this study, we characterize the cyclotides of the medicinal plant Clitoria ternatea (butterfly pea) and investigate their biological activities. Using a combined proteomic and transcriptomic method, we identified 41 novel cyclotide sequences, which we named cliotides, making C. ternatea one of the richest cyclotide-producing plants to date. Selected members of the cationic cliotides display potent antibacterial activity specifically against Gram-negative bacteria with minimal inhibitory concentrations as low as 0.5 MUm. Remarkably, they also possess prominent immunostimulating activity. At a concentration of 1 MUm, cationic cliotides are capable of augmenting the secretion of various cytokines and chemokines in human monocytes at both resting and lipopolysaccharide-stimulated states. Chemokines such as macrophage inflammatory proteins 1alpha and 1beta, interferon gamma induced protein 10, interleukin 8 and tumor necrosis factor alpha were among the most upregulated with up to 129-fold increase in secretion level. These findings suggest cyclotides can serve as potential candidates for novel immunomodulating therapeutics. DATABASE: The protein sequences reported in this paper (cT13-cT21) are available in the UniProt Knowledgebase under the accession numbers C0HJS0, C0HJS1, C0HJS2, C0HJS3, C0HJS4, C0HJS5, C0HJS6, C0HJS7 and C0HJS8, respectively. The transcriptome data in this paper are available at the Sequence Read Archive database (NCBI) under accession number SRR1613316. The protein precursors reported in this paper (ctc13, ctc15, ctc17-ctc19, ctc21-ctc53) are available at GenBank under the accession numbers KT732712, KT732713, KT732714, KT732715, KT732716, KT732717, KT732718, KT732719, KT732720, KT732721, KT732722, KT732723, KT732724, KT732725, KT732726, KT732727, KT732728, KT732729, KT732730, KT732731, KT732732, KT732733, KT732734, KT732735, KT732736, KT732737, KT732738, KT732739, KT732740, KT732741, KT732742, KT732743, KT732744, KT732745, KT732746, KT732747, KT732748 and KT732749, respectively. PMID- 27007914 TI - Precipitation isoscapes for New Zealand: enhanced temporal detail using precipitation-weighted daily climatology. AB - Predictive understanding of precipitation delta(2)H and delta(18)O in New Zealand faces unique challenges, including high spatial variability in precipitation amounts, alternation between subtropical and sub-Antarctic precipitation sources, and a compressed latitudinal range of 34 to 47 degrees S. To map the precipitation isotope ratios across New Zealand, three years of integrated monthly precipitation samples were acquired from >50 stations. Conventional mean annual precipitation delta(2)H and delta(18)O maps were produced by regressions using geographic and annual climate variables. Incomplete data and short-term variation in climate and precipitation sources limited the utility of this approach. We overcome these difficulties by calculating precipitation-weighted monthly climate parameters using national 5-km-gridded daily climate data. This data plus geographic variables were regressed to predict delta(2)H, delta(18)O, and d-excess at all sites. The procedure yields statistically-valid predictions of the isotope composition of precipitation (long-term average root mean square error (RMSE) for delta(18)O = 0.6 0/00; delta(2)H = 5.5 0/00); and monthly RMSE delta(18)O = 1.9 0/00, delta(2)H = 16 0/00. This approach has substantial benefits for studies that require the isotope composition of precipitation during specific time intervals, and may be further improved by comparison to daily and event-based precipitation samples as well as the use of back-trajectory calculations. PMID- 27007915 TI - Preliminary data of the antipancreatic tumor efficacy and toxicity of long circulating and pH-sensitive liposomes containing cisplatin. AB - PURPOSE: Pancreatic cancer is the fourth most common cause of cancer-related death in the USA. This is mainly because of the chemoresistance of this type of tumor; thus, the development of novel therapeutic modalities is needed. METHODS: Long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP) were administered systemically into pancreatic tumor-bearing mice for a period of 14 days. The antitumor efficacy and toxicity of this new treatment method on the basis of cisplatin-loaded liposomes was compared with the classical free-CDDP method. Tc-HYNIC-betaAla-bombesin(7-14) tumor uptake and histopathologic findings were used to monitor and compare the two treatment modalities. RESULTS: The antitumor activity of SpHL-CDDP treatment was shown by (a) decrease in tumor volume, (b) development of tumor necrotic areas, and (c) decrease in Tc-HYNIC betaAla-bombesin(7-14) tumor uptake. Toxicity was evaluated by the development of inflammation and necrotic areas in the kidneys, liver, spleen, and intestine: toxic effects were greater with free-CDDP than SpHL-CDDP. CONCLUSION: SpHL-CDDP showed significant antitumor activity in pancreatic cancer-bearing mice, with lower toxicity in comparison with free-CDDP. PMID- 27007916 TI - A Monooxygenase from Boreostereum vibrans Catalyzes Oxidative Decarboxylation in a Divergent Vibralactone Biosynthesis Pathway. AB - The oxidative decarboxylation of prenyl 4-hydroxybenzoate to prenylhydroquinone has been frequently proposed for the biosynthesis of prenylated (hydro)quinone derivates (sometimes meroterpenoids), yet no corresponding genes or enzymes have so far been reported. A FAD-binding monooxygenase (VibMO1) was identified that converts prenyl 4-hydroxybenzoate into prenylhydroquinone and is likely involved in the biosynthesis of vibralactones and other meroterpenoids in the basidiomycete Boreostereum vibrans. Feeding of 3-allyl-4-hydroxybenzylalcohol, an analogue of the vibralactone pathway intermediate 3-prenyl-4 hydroxybenzylalcohol, generated 20 analogues with different scaffolds. This demonstrated divergent pathways to skeletally distinct compounds initiating from a single precursor, thus providing the first insight into a novel biosynthetic pathway for 3-substituted gamma-butyrolactones from a shikimate origin. PMID- 27007917 TI - The Role of Color and Morphologic Characteristics in Dermoscopic Diagnosis. AB - IMPORTANCE: Both colors and structures are considered important in the dermoscopic evaluation of skin lesions but their relative significance is unknown. OBJECTIVE: To determine if diagnostic accuracy for common skin lesions differs between gray-scale and color dermoscopic images. DESIGN, SETTING, AND PARTICIPANTS: A convenience sample of 40 skin lesions (8 nevi, 8 seborrheic keratoses, 7 basal cell carcinomas, 7 melanomas, 4 hemangiomas, 4 dermatofibromas, 2 squamous cell carcinomas [SCCs]) was selected and shown to attendees of a dermoscopy course (2014 Memorial Sloan Kettering Cancer Center dermoscopy course). Twenty lesions were shown only once, either in gray-scale (n = 10) or color (n = 10) (nonpaired). Twenty lesions were shown twice, once in gray-scale (n = 20) and once in color (n = 20) (paired). Participants provided their diagnosis and confidence level for each of the 60 images. Of the 261 attendees, 158 participated (60.5%) in the study. Most were attending physicians (n = 76 [48.1%]). Most participants were practicing or training in dermatology (n = 144 [91.1%]). The median (interquartile range) experience evaluating skin lesions and using dermoscopy of participants was 6 (13.5) and 2 (4.0) years, respectively. MAIN OUTCOMES AND MEASURES: Diagnostic accuracy and confidence level of participants evaluating gray-scale and color images. Two separate analyses were performed: (1) an unpaired evaluation comparing gray-scale and color images shown either once or for the first time, and (2) a paired evaluation comparing pairs of gray-scale and color images of the same lesion. RESULTS: In univariate analysis of unpaired images, color images were less likely to be diagnosed correctly compared with gray-scale images (odds ratio [OR], 0.8; P < .001). Using gray-scale images as the reference, multivariate analyses of both unpaired and paired images found no association between correct lesion diagnosis and use of color images (OR, 1.0; P = .99, and OR, 1.2; P = .82, respectively). Stratified analysis of paired images using a color by diagnosis interaction term showed that participants were more likely to make a correct diagnosis of SCC and hemangioma in color (P < .001 for both comparisons) and dermatofibroma in gray scale (P < .001). CONCLUSIONS AND RELEVANCE: Morphologic characteristics (ie, structures and patterns), not color, provide the primary diagnostic clue in dermoscopy. Use of gray-scale images may improve teaching of dermoscopy to novices by emphasizing the evaluation of morphology. PMID- 27007918 TI - '"Why me, why now?" Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection. AB - BACKGROUND: The prevalence of nontuberculous mycobacterial (NTM) disease is rising. An understanding of known risk factors for disease sheds light on the immunological and physical barriers to infection, and how and why they may be overcome. This review focuses on human NTM infection, supported by experimental and in vitro data of relevance to the practising clinician who seeks to understand why their patient has NTM infection and how to further investigate. DISCUSSION: First, the underlying immune response to NTM disease is examined. Important insights regarding NTM disease susceptibility come from nature's own knockouts, the primary immune deficiency disorders. We summarise the current knowledge surrounding interferon-gamma (IFNgamma)-interleukin-12 (IL-12) axis abnormalities, followed by a review of phagocytic defects, T cell lymphopenia and rarer genetic conditions known to predispose to NTM disease. We discuss how these define key immune pathways involved in the host response to NTM. Iatrogenic immunosuppression is also important, and we evaluate the impact of novel biological therapies, as well as bone marrow transplant and chemotherapy for solid organ malignancy, on the epidemiology and presentation of NTM disease, and discuss the host defence dynamics thus revealed. NTM infection and disease in the context of other chronic illnesses including HIV and malnutrition is reviewed. The role of physical barriers to infection is explored. We describe how their compromise through different mechanisms including cystic fibrosis, bronchiectasis and smoking-related lung disease can result in pulmonary NTM colonisation or infection. We also summarise further associations with host factors including body habitus and age. We use the presented data to develop an over-arching model that describes human host defences against NTM infection, where they may fail, and how this framework can be applied to investigation in routine clinical practice. PMID- 27007919 TI - Modulation of circulating vasoactive peptides and extracellular matrix proteins are two novel mechanisms in the cardioprotective action of acarbose. AB - BACKGROUND: Acarbose, an alpha-glucosidase inhibitor, unexpectedly reduced the incidence of hypertension and cardiovascular endpoints in the STOP-NIDDM study. Based on the growing evidence of a link between vasoregulatory peptides and metabolic traits, we hypothesized that changes of the Glycemic Index by acarbose may modulate vasoregulatory peptide levels via regulation of postprandial metabolism. METHODS: Subjects with type 2 diabetes and with metabolic syndrome were treated with acarbose (12 weeks, 300mg/d) in a double-blind, placebo controlled, cross-over intervention. Changes in fasting and postprandial levels of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM), WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as well as fasting and postprandial glucose/insulin levels in the liquid meal test were assessed. RESULTS: Acarbose strongly decreased postprandial insulin concentrations in subjects with metabolic syndrome (P=0.004), and postprandial glucose excursions in both groups. Postprandial MR-proANP and CT-proET-1 levels increased after acarbose treatment (P<0.01 and P<0.05, respectively) in subjects with metabolic syndrome only. No effect of acarbose treatment on MR-prADM was observed in both groups. All three peptides were correlated with each over, but neither with insulin sensitivity in euglycemic clamps, nor with adiponectin levels. WISP1 decreased after acarbose treatment in subjects with metabolic syndrome. CONCLUSIONS: Plasma MR- proANP and CT-proET-1 concentrations, but not MR-prADM concentrations, were affected by treatment with acarbose over 12 weeks. Our findings provide new possible mechanisms of acarbose action in diabetes and metabolic syndrome. PMID- 27007920 TI - Combined geometric and algebraic solutions for removal of bSSFP banding artifacts with performance comparisons. AB - PURPOSE: Balanced steady state free precession (bSSFP) imaging suffers from off resonance artifacts such as signal modulation and banding. Solutions for removal of bSSFP off-resonance dependence are described and compared, and an optimal solution is proposed. THEORY AND METHODS: An Algebraic Solution (AS) that complements a previously described Geometric Solution (GS) is derived from four phase-cycled bSSFP datasets. A composite Geometric-Algebraic Solution (GAS) is formed from a noise-variance-weighted average of the AS and GS images. Two simulations test the solutions over a range of parameters, and phantom and in vivo experiments are implemented. Image quality and performance of the GS, AS, and GAS are compared with the complex sum and a numerical parameter estimation algorithm. RESULTS: The parameter estimation algorithm, GS, AS, and GAS remove most banding and signal modulation in bSSFP imaging. The variable performance of the GS and AS on noisy data justifies generation of the GAS, which consistently provides the highest performance. CONCLUSION: The GAS is a robust technique for bSSFP signal demodulation that balances the regional efficacy of the GS and AS to remove banding, a feat not possible with prevalent techniques. Magn Reson Med 77:644-654, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27007921 TI - Correction: Evaluation of High-Throughput Genomic Assays for the Fc Gamma Receptor Locus. PMID- 27007922 TI - Rapid and Robust PCR-Based All-Recombinant Cloning Methodology. AB - We report here a PCR-based cloning methodology that requires no post-PCR modifications such as restriction digestion and phosphorylation of the amplified DNA. The advantage of the present method is that it yields only recombinant clones thus eliminating the need for screening. Two DNA amplification reactions by PCR are performed wherein the first reaction amplifies the gene of interest from a source template, and the second reaction fuses it with the designed expression vector fragments. These vector fragments carry the essential elements that are required for the fusion product selection. The entire process can be completed in less than 8 hours. Furthermore, ligation of the amplified DNA by a DNA ligase is not required before transformation, although the procedure yields more number of colonies upon transformation if ligation is carried out. As a proof-of-concept, we show the cloning and expression of GFP, adh, and rho genes. Using GFP production as an example, we further demonstrate that the E. coli T7 express strain can directly be used in our methodology for the protein expression immediately after PCR. The expressed protein is without or with 6xHistidine tag at either terminus, depending upon the chosen vector fragments. We believe that our method will find tremendous use in molecular and structural biology. PMID- 27007924 TI - [Not Available]. PMID- 27007925 TI - Improving performance on core processes of care. AB - PURPOSE OF REVIEW: This article describes the recent literature on using extrinsic and intrinsic motivators to improve performance on core processes of care, highlighting literature that describes general frameworks for quality improvement work. RECENT FINDINGS: The literature supporting the effectiveness of extrinsic motivators to improve quality is generally positive for public reporting of performance, with mixed results for pay-for-performance. A four element quality improvement framework developed by The Armstrong Institute at Johns Hopkins Medicine was developed with intrinsic motivation in mind. The clear definition and communication of goals are important for quality improvement work. Training clinicians in improvement science, such as lean sigma, teamwork, or culture change provides clinicians with the skills they need to drive the improvement work. Peer learning communities offer the opportunity for clinicians to engage with each other and offer support in their work. The transparent reporting of performance helps ensure accountability of performance ranging from individual clinicians to governance. SUMMARY: Quality improvement work that is led by and engages clinicians offers the opportunity for the work to be both meaningful and sustainable. The literature supports approaching quality improvement work in a systematic way, including the key elements of communication, infrastructure building, training, transparency, and accountability. PMID- 27007926 TI - [Evidence-based hip prostheses: more high-quality prostheses used after introduction of a classification system]. AB - OBJECTIVE: To determine the effect of an evidence-based classification list on use of total hip prostheses of proven quality in the Netherlands. DESIGN: Observational study. METHOD: The Netherlands Orthopaedic Association (NOV) drew up a classification list for total hip prostheses in 2013. This classification list considered total hip prostheses to be of proven quality when the average percent of revision was <= 10% after 10 years of follow-up (category 1A) or <= 5% after 5 years of follow-up (category 1B). Data from the Dutch National Orthopaedic Implant Registry Register (LROI) were used to determine the effect of the classification list on the use of hip prostheses of proven quality in the Netherlands. All patients, operations and prosthesis characteristics of the hip prostheses used in the Netherlands were registered in the LROI. We selected details of all interventions in which a hip prosthesis was implanted in patients with 'osteoarthritis' as primary diagnosis between 2012 and 2014 from the LROI. The prostheses could be classified as 1A, 1B or 'not 1A or 1B' by means of the implant code of the acetabular and femoral components. We took 2012 as the reference year. RESULTS: In the reference year, 84% of the acetabular components and 94% of the femoral components were category 1A or 1B. In 2013 these percentages had increased to 89% and 95%, respectively; in 2014 the percentages had increased to 92% and 97%. CONCLUSION: After implementation of the NOV classification list there was an increase in the percentage of total hip prostheses of proven quality, which means that patient care has become better and safer. PMID- 27007927 TI - [Complications after vaginal mesh surgery]. AB - Pelvic organ prolapse (POP) is a common problem. There is a significant risk of recurrent POP after surgery. To reduce this risk vaginal meshes have been introduced. Mesh surgery has very specific complications that are not always recognised as most physicians are not aware of the symptoms. Possible solutions to these problems are not well known either. In this clinical lesson we describe two patients who developed complications following vaginal mesh surgery which had taken place several years after the index surgery. Although the symptoms were specific to vaginal mesh surgery, they were only recognised long after they had developed. Removal of the implant resolved the symptoms. Based on the complicated diagnosis and treatment of mesh-related complications we recommend that care for these patients should be centralised at a centre with a multidisciplinary team that has the surgical expertise to resolve the symptoms. PMID- 27007928 TI - [3D bioprinting of cartilage: challenges concerning the reconstruction of a burned ear]. AB - Reconstruction of a severely maimed ear is a major challenge. The ear is highly flexible yet tough, and has a very complex three-dimensional shape. Reconstruction of a patient's burned ear is even more complex due to surrounding tissue damage. Not only does this hamper reconstruction options, it also increases the likelihood of issues when using synthetic implant materials. In such cases, rib cartilage is the preferred option, but this tissue has practical limitations too. For these reasons, tissue engineering and 3D bioprinting may have the potential to create personalized cartilage implants for burns patients. However, 3D bioprinting is a tool to facilitate the reconstruction, and not by itself the Holy Grail. The clinical application of this technique is still at a very early stage. Nevertheless, we expect that 3D bioprinting can be utilised for facial reconstruction following burns come 2020. PMID- 27007930 TI - [Development and future prospects of cataract surgery]. AB - In recent decades, enormous progress has been made in the development of intraocular lenses (IOLs) and cataract surgery. Before the development of the IOL, a cataract would cause impairment or loss of vision. Nowadays, cataract extractions are among the most frequently performed surgeries worldwide. The current cataract procedure is associated with a very low incidence of intra- and postoperative complications and satisfactory postoperative visual outcomes. Due to the increasing number of cataract surgeries performed annually, and an ageing population, development of IOLs and surgical techniques continues apace. PMID- 27007929 TI - [Neuromodulation in severe neuropathic pain]. AB - Pain relief in patients with chronic neuropathic pain can be difficult to accomplish. If pharmacological treatment combined with a form of physical therapy and psychological support does not lead to improvement, nerve blocks and rehabilitation can be considered. Appropriately screened patients with persistent incapacitating pain may respond to neuromodulation. A specific form of this technique - spinal cord stimulation - delivers electric pulses via an implanted electrode connected to a battery in the epidural space around the spinal cord. We describe three patients, two of whom had persistent leg pain after disc surgery. The third patient suffered from diabetic neuropathy. Despite thorough pre procedural screening by an anaesthetist-pain specialist, psychologist, physical therapist and specialised nurse, spinal cord stimulation failed in one patient. Psycho-social factors, inadequate coping skills and depression may lead to inadequate improvement and failure of this therapy. PMID- 27007931 TI - [IDEAL as a model for the evaluation of implants]. AB - Medical devices have to be tested for safety before they can be brought onto the market; effectiveness does not have to be demonstrated. The 'IDEAL model' is in place for the development and evaluation of new surgical interventions and procedures; 'IDEAL' stands for the 5 phases of the model: Idea, Development, Exploration, Assessment and Long-term study. The model is based on the assumption that innovation and evaluation should be interwoven from concept through to the, preferably randomised, clinical trial phase. Prospective registration of new interventions from the pre-clinical development phase onwards can prevent waste of money and effort, as unsuccessful 'new' registered interventions will not have to be developed again in the same manner. The IDEAL model, with a few adaptations, also seems to be a practically useful and suitable model for new medical devices. It will allow patients efficient access to new interventions and medical devices for which the safety and effectiveness has been sufficiently clinically established. PMID- 27007932 TI - [Registries for implants and new interventions]. AB - An increasing number of registries are being set up in healthcare. Their development is sometimes guided by an explicit desire to control the unknown, as with most registries initiated for new devices as part of coverage with evidence development schemes. By definition, registries cannot answer questions about the effectiveness of interventions. At best, they document the outcomes after the intervention; it will remain unknown what the outcome would have been with a different implant or device, or without one. Nonetheless, registries can provide useful information for other purposes: for documenting appropriate use, for monitoring complications and revisions, for comparing observed outcomes against predicted outcomes, and for comparing different types of devices used for the same purpose. Registries can also assist quality improvement efforts by participating professionals and healthcare organisations. PMID- 27007933 TI - [Medical education in the digital era; opportunities for the Netherlands]. AB - The next generation of physicians enters a job market of high-tech medicine; detailed technical knowledge of this technology is therefore a prerequisite. However, teaching on technology does not currently form an integral part of the medicine degree curriculum. We should consider if a generic medicine degree is still a valid framework, or whether students should be offered to move into different specialties at an earlier stage. By applying the latter approach, we can produce a generation of physicians prepared for the challenges thrown at them in a constantly changing, high-tech, professional environment. PMID- 27007934 TI - [Implant registry and patient data; physician needs to be aware of privacy laws]. AB - In 2015 a national implant registry (LIR) was established in the Netherlands. The aim of this registry is to enable the quick identification of patients with implants that subsequently cause problems. To this end, the controller of the registry collects patient data from hospitals and individual physicians. The privacy laws apply to the LIR and the disclosing hospitals and physicians. Both the controller of the registry and those who submit data to it should be aware of these laws, particularly in view of the high administrative penalties that have recently been imposed on breaches of the laws on privacy and the risk of liability claims. PMID- 27007935 TI - [Street doctors warn of epidemic of uninsured homeless persons in the Netherlands]. AB - Over the past few years, the Netherlands Street Doctors Group, a national network of doctors and nurses providing outreach primary care to homeless people in the Netherlands, has observed a growing number of homeless patients who do not have health insurance resulting in their access to healthcare services and medication being limited. In this article we raise the alarm about the epidemic of uninsured Dutch homeless. We explain and comment on the reasons why people are no longer insured and elaborate on the regulations and obligations related to homelessness and the characteristics of consumers and providers of social and medical services. We describe how difficult it is for homeless people to become re insured as in order to follow a complex set of requirements commitment and patience are necessary. For most homeless patients, the re-insurance process requires the personal guidance and support of a motivated case manager. Consequently, we suggest that policy makers and service providers should have a better understanding of factors contributing to being uninsured and more compassion for those who are. PMID- 27007936 TI - [The Starr-Edwards heart valve: one of the oldest mechanical heart valves still functioning today]. AB - In the 1960s, the Starr-Edwards valve was the first artificial heart valve to be successfully implanted in humans. This valve has now been in use for decades with outstanding results: patients whose life expectancy had previously been short acquired a good prognosis with this development. Nowadays the Starr-Edwards valve is not used anymore, but patients are being described today in whom these valves are still functioning well after more than 40 years. PMID- 27007937 TI - [Is a physician liable for an unsafe implant?]. AB - In recent years, various incidents involving unsafe implants have drawn a lot of attention. Examples include problems with breast prostheses (PIP implants), artificial hips (metal-on-metal hip prostheses) and synthetic mesh implants, and possible dysfunctional leads of implantable cardioverter defibrillators. This article highlights the regulations concerning physicians' liability if it transpires that the implants they used for the treatment of patients prove to be unsafe. PMID- 27007938 TI - [The Netherlands smokefree: doctors make a statement. Politicians should act now]. AB - In 2014, 23% of the adult Dutch population smoked, and 17% smoked daily. Although smoking prevalence has declined since 2010, when it was still 28%, there is huge scope for further reductions, which are highly necessary in view of the fact that smoking is still by far the most important cause of disease and premature death in the Netherlands. Over the last few years, successive Dutch governments have been reluctant to take radical action against smoking, but among healthcare professionals the conviction is rising that more should be done. This is exemplified by the Netherlands Smokefree Alliance, which unites more than 50 healthcare and related organisations in a movement to create a first, completely smokefree generation starting with all newborns in 2017. Now that even the Royal Dutch Medical Association (KNMG) has issued a statement on tobacco control, it is time for politicians to take action. PMID- 27007939 TI - Mindful Attention to Variability Intervention and Successful Pregnancy Outcomes. AB - OBJECTIVE: Based on a definition of mindfulness as actively noticing novelty (Langer, 1989; Langer, Blank, & Chanowitz, 1978), the present study sought to examine whether mindfulness training (attention to sensation variability) resulted in better childbirth outcomes for both mother and infant. METHOD: At Weeks 25-30 of pregnancy, mindful instructions to attend to the variability of their positive and negative physical sensations were given to 1 group of participants and compared with 2 control groups (N = 105). The Langer Mindfulness Scale was used to assess the relationship between trait mindfulness and health outcomes. RESULTS: Findings showed that trait mindfulness predicted the well being of expecting mothers and better neonatal outcomes. Mindfulness training resulted in better health for the expecting mother. CONCLUSION: Findings suggest that mindfulness without meditation can be easily taught and may enhance the pregnancy experience for mother and fetus. PMID- 27007940 TI - Measuring child maltreatment using multi-informant survey data: a higher-order confirmatory factor analysis. AB - OBJECTIVE: To investigate the validity and reliability of a multi-informant approach to measuring child maltreatment (CM) comprising seven questions assessing CM administered to children and their parents in a large community sample. METHODS: Our sample comprised 2,512 children aged 6 to 12 years and their parents. Child maltreatment (CM) was assessed with three questions answered by the children and four answered by their parents, covering physical abuse, physical neglect, emotional abuse and sexual abuse. Confirmatory factor analysis was used to compare the fit indices of different models. Convergent and divergent validity were tested using parent-report and teacher-report scores on the Strengths and Difficulties Questionnaire. Discriminant validity was investigated using the Development and Well-Being Assessment to divide subjects into five diagnostic groups: typically developing controls (n = 1,880), fear disorders (n = 108), distress disorders (n = 76), attention deficit hyperactivity disorder (n = 143) and oppositional defiant disorder/conduct disorder (n = 56). RESULTS: A higher-order model with one higher-order factor (child maltreatment) encompassing two lower-order factors (child report and parent report) exhibited the best fit to the data and this model's reliability results were acceptable. As expected, child maltreatment was positively associated with measures of psychopathology and negatively associated with prosocial measures. All diagnostic category groups had higher levels of overall child maltreatment than typically developing children. CONCLUSIONS: We found evidence for the validity and reliability of this brief measure of child maltreatment using data from a large survey combining information from parents and their children. PMID- 27007941 TI - DSM-IV-defined anxiety disorder symptoms in a middle-childhood-aged group of Malaysian children using the Spence Children's Anxiety Scale. AB - INTRODUCTION: Pediatric anxiety disorders are the most common mental health disorders in the middle-childhood age group. The purpose of this study is to assess anxiety disorder symptoms, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), in a large community sample of low socioeconomic level rural children and to investigate some of the psychometric properties (internal consistency, construct and convergent validity and items rated as often or always experienced) of the Malay version of the Spence Children's Anxiety Scale - Child version (SCAS-C). METHOD: Six hundred children aged 9-11 and 424 of their parents completely answered the child or parent versions of the SCAS. RESULTS: Results indicated that the internal reliability of subscales were moderate to adequate. Significant correlations between child and parent reports supported the measure's concurrent validity. Additionally, anxiety levels in this Malaysian sample were lower than among South African children and higher than among their Western peers. There were both similarities and differences between symptom items reported as often or always experienced by Malaysian students and by children from other cultures. Confirmatory factor analysis provided evidence of the existence of five inter correlated factors for anxiety disorders based on SCAS-C. CONCLUSION: Although some of the instrument's psychometric properties deviated from those observed in some other countries, it nevertheless appears to be useful for assessing childhood anxiety symptoms in this country. PMID- 27007942 TI - Depression and anxiety in individuals with amyotrophic lateral sclerosis: a systematic review. AB - INTRODUCTION: Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this systematic review is to identify the prevalence of these mood disorders in the literature. METHODS: We searched the PubMed, HighWire, MEDLINE, SciELO, LILACS and ScienceDirect databases. Literature was selected for review in two stages, according to eligibility criteria. The first stage involved searching databases and checking titles and abstracts. The second step consisted of reading complete articles and excluding those that did not meet the inclusion criteria. The inclusion criteria were articles written in Portuguese, English or Spanish, published in the last five years and involving people with ALS diagnosed according to the El Escorial criteria. RESULTS: The database searches returned a total of 1,135 titles and abstracts and then 1,117 of these were excluded. Eighteen articles were selected for review. The 12-item Amyotrophic Lateral Sclerosis Depression Inventory (ADI-12) was the only instrument designed specifically to assess depression in ALS, but it was only used in three studies. No instruments specifically designed for anxiety in ALS were used. A large number of studies found presence and slight increase of anxiety disorders. There was considerable large variation in the results related to depressive disorders, ranging from moderate depression to an absence of symptoms. CONCLUSIONS: Patients with ALS may exhibit symptoms of depression and anxiety at different levels, but there is a need for studies using specific instruments with larger samples in order to ascertain the prevalence of symptoms in ALS and the factors associated with it. PMID- 27007943 TI - Cytochrome P450 17A1 Inhibitor Abiraterone Acetate Counteracts the Heat Shock Protein 27's Cell Survival Properties in Prostate Cancer Cells. AB - INTRODUCTION: Inhibition of androgen synthesis by abiraterone acetate (AA) entails enhanced overall survival rates and clinical benefit for patients with locally advanced and metastasized prostate cancer (PC). The expression of heat shock protein 27 (HSP27) is generally associated with cytoprotection and was demonstrated to mediate chemoresistance under cytostatic therapy, for instance, docetaxel treatment. In this study, we investigated the impact of AA treatment on HSP27 expression and PC cell growth. MATERIALS AND METHODS: HSP27 expression levels in docetaxel and AA-treated PC cell lines LNCaP and PC-3 were determined by SDS PAGE and Western blot analysis. Proliferation assays were performed using a CASY Cell Counter and Analyzer Model TT (Roche Applied Science). RESULTS: Despite significantly increased HSP27 expression in PC cells incubated with docetaxel, Western blot analysis implicated a significant reduction of the cytoprotective HSP27 in AA-treated PC cells. Notably, HSP27 stably overexpressed in PC-3-HSP27 cells did not appear as an HSP27-mediated proliferation benefit in the presence of AA as shown in docetaxel incubation studies. CONCLUSION: In contrast to repeatedly demonstrated HSP27-driven chemoresistance related to chemotherapeutics, our results may constitute a broader molecular mode of action of AA chemotherapy. AA efficacy may exert an HSP27 suppressive role that goes beyond the primarily assumed inhibition of androgen biosynthesis. PMID- 27007944 TI - Surface-controlled contact printing for nanowire device fabrication on a large scale. AB - Assembly strategies for functional nanowire devices that merge bottom-up and top down technologies have been debated for over a decade. Although several breakthroughs have been reported, nanowire device fabrication techniques remain generally incompatible with large-scale and high-yield top-down microelectronics manufacturing. Strategies enabling the controlled transfer of nanowires from the growth substrate to pre-defined locations on a target surface would help to address this challenge. Based on the promising concept of mechanical nanowire transfer, we developed the technique of surface-controlled contact printing, which is based purely on dry friction between a nanowire and a target surface. Surface features, so-called catchers, alter the local frictional force or deposition probability and allow the positioning of single nanowires. Surface controlled contact printing extends the current scope of nanowire alignment strategies with the intention to facilitate efficient nanowire device fabrication. This is demonstrated by the simultaneous assembly of 36 nanowire resistors within a chip area of greater than 2 cm(2) aided only by mask-assisted photolithography. PMID- 27007945 TI - Longitudinal Changes in Resting-State Cerebral Activity in Patients with First Episode Schizophrenia: A 1-Year Follow-up Functional MR Imaging Study. AB - Purpose To determine whether the brain functional abnormalities of drug-naive first-episode schizophrenia are reduced after 1 year of undergoing antipsychotic treatment and whether pretreatment resting-state functional magnetic resonance (MR) imaging parameters are associated with longitudinal changes in clinical symptoms. Materials and Methods This prospective study was approved by the local ethical committee, and written informed consent was obtained from all participants. Twenty antipsychotic-naive first-episode patients with schizophrenia and 16 healthy individuals were recruited and underwent resting state functional MR imaging at baseline and again at 1-year follow-up, by which time significant clinical improvement was seen. The amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were analyzed with analysis of covariance. Results The amount of ALFF in the right inferior parietal lobule (IPL) and orbitofrontal cortex (OFC) and the amount of FC between the bilateral IPLs significantly increased over the follow-up period, and the amount of ALFF in the right occipital gyrus was reduced (P < .050, AlphaSim corrected [ http://afni.nimh.nih.gov/pub/dist/doc/manual/AlphaSim.pdf ]), returning toward normal levels. Furthermore, the degree of alteration in ALFF values in the right OFC (P = .037) and occipital gyrus (P = .002) at baseline was significantly correlated with the magnitude of the normalization in those regions at 1-year follow-up. In contrast, abnormalities of ALFF in the bilateral thalamus, ventral medial prefrontal cortex, precuneus, and right amygdala and of FC between the right OFC and the dorsal medial prefrontal cortex at baseline did not improve in patients at 1-year follow-up. Conclusion These findings show that some, but not all, neurophysiologic alterations that occur during the acute phase of schizophrenia are normalized in the context of clinical improvement and suggest therapeutic implications for exploration of which alterations in regional and network-level brain function evolve over time in patients with schizophrenia and which reflect persistent pathologic traits. Online supplemental material is available for this article. PMID- 27007946 TI - Myeloid Sarcoma of the Hepatobiliary System: A Case Series and Review of the Literature. AB - Myeloid sarcoma (MS) is a rare extramedullary presentation of myeloid malignancies, most commonly seen in association with acute myeloid leukemia (AML). Although MS can develop in any organ, the involvement of the hepatobiliary system is rare. With clinical manifestations of jaundice, abdominal pain and other gastrointestinal symptoms, MS presenting at this location can be a challenge to diagnose, particularly in patients with no known history of hematologic malignancy. This may cause delay in proper management. Here we report 3 cases from a single institution and a review of the literature concerning the epidemiology, clinical presentation, treatment and outcomes in patients with MS of the liver, biliary tree and pancreas. PMID- 27007947 TI - Comparison of Resting Energy Expenditure Between Cancer Subjects and Healthy Controls: A Meta-Analysis. AB - There is conflicting evidence surrounding the extent of changes in resting energy expenditure (REE) in cancer. This meta-analysis aimed to establish the mean difference in REE, as kilojoules per kilogram fat-free mass, among cancer patients when compared to healthy control subjects. The secondary aim was to determine differences among different cancer types. PubMed, Cochrane Library, Medline, Science Direct, Scopus, Web of Science, Wiley Online Library, and ProQuest Central were searched from the earliest records until March 2014. Studies were included if measured REE was reported as kilojoules or kilocalories per kilogram fat-free mass (FFM) in adult subjects with cancer. Twenty-seven studies were included in the meta-analysis. Fourteen studies included both cancer (n = 1453) and control (n = 1145) groups. The meta-analysis shows an average increase in REE of 9.66 (95% confidence interval: 3.34, 15.98) kJ/kgFFM/day in cancer patients when compared to control subjects. Heterogeneity was detected (P < 0.001) which suggest variations in REE among cancer types. Elevations are most noticeable in patients with cancers of metabolically demanding organs. PMID- 27007949 TI - 2015 Research Forum Poster Session and Competition: Winners. PMID- 27007948 TI - Incidentally Raised Cardiac Troponin I Has a Worse Prognosis in Older Patients Compared to Those with Normal Cardiac Troponin I and Patients with Acute Coronary Syndrome: A Cohort Study. AB - BACKGROUND: Incidentally elevated cardiac troponin I (cTnI) levels are common in acutely unwell older patients. However, little is known about how this impacts on the prognosis of these patients. OBJECTIVE: We aimed to investigate whether incidentally elevated cTnI levels (group 1) are associated with poorer outcome when compared to age- and sex-matched patients without an elevated cTnI level (group 2), and to patients diagnosed with acute coronary syndrome (group 3). PATIENTS AND METHODS: This prospective, matched cohort study placed patients >=75 years old who were admitted to a University teaching hospital into groups 1-3, based on the cTnI levels and underlying diagnosis. Outcomes were compared between the groups using mixed-effects regression models and adjusted for renal function and C-reactive protein. All-cause mortality at discharge, at 1 month and 3 months, alongside the length of hospital stay (LOS), were recorded. RESULTS: In total, 315 patients were included, with 105 patients in each of the 3 groups. The mean age was 84.8 +/- 5.5 years, with 41.9% males. All patients were followed up for 3 months. The percent all-cause mortality at discharge and the LOS for groups 1, 2 and 3 were 12.4, 3.8 and 8.6% and 11.2, 8.5 and 7.7 days, respectively. Group 1 had significantly increased mortality at 3 months [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.12-6.96; p = 0.040] and LOS (OR 1.39, 95% CI 1.08 1.79; p = 0.008) compared to group 2 and did not differ significantly when compared to 3-month mortality (OR 2.39, 95% CI 0.91-6.29; p = 0.079) or LOS (OR 1.26, 95% CI 0.96-1.66; p = 0.097) in group 3. CONCLUSION: There is a significant association between an incidental rise in cTnI level with mortality and LOS in older patients. Further research is required to evaluate whether a more systematic management of these patients would improve the prognosis. PMID- 27007950 TI - Endocranial Morphology of the Primitive Nodosaurid Dinosaur Pawpawsaurus campbelli from the Early Cretaceous of North America. AB - BACKGROUND: Ankylosaurs are one of the least explored clades of dinosaurs regarding endocranial anatomy, with few available descriptions of braincase anatomy and even less information on brain and inner ear morphologies. The main goal of this study is to provide a detailed description of the braincase and internal structures of the Early Cretaceous nodosaurid Pawpawsaurus campbelli, based on recently made CT scans. METHODOLOGY/PRINCIPAL FINDINGS: The skull of Pawpawsaurus was CT scanned at University of Texas at Austin (UTCT). Three dimensional models were constructed using Mimics 18.0 (Materialise). The digital data and further processed 3D models revealed inaccessible anatomic structures, allowing a detailed description of the lateral wall of the braincase (obscured by other bones in the articulated skull), and endocranial structures such as the cranial endocast, the most complete inner ear morphology for a nodosaurid, and the interpretation of the airflow system within the nasal cavities. CONSLUSIONS/SIGNIFICANCE: The new information on the endocranial morphology of Pawpawsaurus adds anatomical data to the poorly understand ankylosaur paleoneurology. The new set of data has potential use not only in taxonomy and phylogeny, but also in paleobiological interpretations based on the relative development of sense organs, such as olfaction, hearing and balance. PMID- 27007951 TI - Elliptic Curve Cryptography-Based Authentication with Identity Protection for Smart Grids. AB - In a smart grid, the power service provider enables the expected power generation amount to be measured according to current power consumption, thus stabilizing the power system. However, the data transmitted over smart grids are not protected, and then suffer from several types of security threats and attacks. Thus, a robust and efficient authentication protocol should be provided to strength the security of smart grid networks. As the Supervisory Control and Data Acquisition system provides the security protection between the control center and substations in most smart grid environments, we focus on how to secure the communications between the substations and smart appliances. Existing security approaches fail to address the performance-security balance. In this study, we suggest a mitigation authentication protocol based on Elliptic Curve Cryptography with privacy protection by using a tamper-resistant device at the smart appliance side to achieve a delicate balance between performance and security of smart grids. The proposed protocol provides some attractive features such as identity protection, mutual authentication and key agreement. Finally, we demonstrate the completeness of the proposed protocol using the Gong-Needham-Yahalom logic. PMID- 27007952 TI - Incipient Social Groups: An Analysis via In-Vivo Behavioral Tracking. AB - Social psychology is fundamentally the study of individuals in groups, yet there remain basic unanswered questions about group formation, structure, and change. We argue that the problem is methodological. Until recently, there was no way to track who was interacting with whom with anything approximating valid resolution and scale. In the current study we describe a new method that applies recent advances in image-based tracking to study incipient group formation and evolution with experimental precision and control. In this method, which we term "in vivo behavioral tracking," we track individuals' movements with a high definition video camera mounted atop a large field laboratory. We report results of an initial study that quantifies the composition, structure, and size of the incipient groups. We also apply in-vivo spatial tracking to study participants' tendency to cooperate as a function of their embeddedness in those crowds. We find that participants form groups of seven on average, are more likely to approach others of similar attractiveness and (to a lesser extent) gender, and that participants' gender and attractiveness are both associated with their proximity to the spatial center of groups (such that women and attractive individuals are more likely than men and unattractive individuals to end up in the center of their groups). Furthermore, participants' proximity to others early in the study predicted the effort they exerted in a subsequent cooperative task, suggesting that submergence in a crowd may predict social loafing. We conclude that in vivo behavioral tracking is a uniquely powerful new tool for answering longstanding, fundamental questions about group dynamics. PMID- 27007953 TI - Improving alcohol screening for college students: Screening for alcohol misuse amongst college students with a simple modification to the CAGE questionnaire. AB - OBJECTIVE: To improve the CAGE (Cut down, Annoyed, Guilty, Eye opener) questionnaire's predictive accuracy in screening college students. PARTICIPANTS: The sample consisted of 219 midwestern university students who self-administered a confidential survey. METHODS: Exploratory factor analysis, confirmatory factor analysis, receiver operating characteristics (ROC), and Cronbach's alpha were used to analyze factor structure, validity, and reliability. RESULTS: The modified CAGE correctly classified students with alcohol abuse ("AA students"; area under the curve [AUC] = 0.7765) and students with alcohol dependency ("AD students"; AUC = 0.8392) more often than CAGE (AA students: AUC = 0.6977; AD students: AUC = 0.7437), and these differences are statistically significant (AA students: chi(2)(1) = 14.72, p < .001; AD students: chi(2)(1) = 7.71, p < .01). Using 2-point cut scores, CAGE correctly identified 59.38% of AD students as AD, whereas the modified CAGE correctly identified 87% of AD students as AD. Using 1 point cut scores, CAGE correctly identified 65% AA students, whereas the modified CAGE identified 85.29%. CONCLUSIONS: The modified CAGE has better accuracy than CAGE in predicting AA and AD among college populations. PMID- 27007955 TI - Clinicopathological analysis of salivary gland tissue from patients with IgG4 related disease. AB - Conclusion The diagnosis of immunoglobulin G4-related disease (IgG4-RD) should be based on the morphology of tissue biopsy, and this study recommends a submandibular gland (SMG) biopsy for accurate diagnosis and to exclude malignant disease. Objective To clarify which type of biopsy specimen (SMG or labial salivary gland [LSG]) should be taken from patients with IgG4-RD. Methods This study included 33 patients with IgG4-RD (21 women; 12 men) who were subjected to both SMG and LSG biopsies at Sapporo Medical University between 2011-2015. Tissues obtained from the SMG and LSG specimens were evaluated. Results All SMG specimens satisfied the diagnostic criteria for IgG4-RD, whereas 19 (57.6%) LSG specimens satisfied the diagnostic criteria for IgG4-RD. Histological evaluation showed fibrosis in all the SMG specimens and in eight LSG specimens (24.2%). Obliterative phlebitis was seen in nine SMG specimens (27.3%), but it was absent in all the LSG specimens. PMID- 27007956 TI - Signaling pathways for stress responses and adaptation in Aspergillus species: stress biology in the post-genomic era. AB - Aspergillus species are among the most important filamentous fungi in terms of industrial use and because of their pathogenic or toxin-producing features. The genomes of several Aspergillus species have become publicly available in this decade, and genomic analyses have contributed to an integrated understanding of fungal biology. Stress responses and adaptation mechanisms have been intensively investigated using the accessible genome infrastructure. Mitogen-activated protein kinase (MAPK) cascades have been highlighted as being fundamentally important in fungal adaptation to a wide range of stress conditions. Reverse genetics analyses have uncovered the roles of MAPK pathways in osmotic stress, cell wall stress, development, secondary metabolite production, and conidia stress resistance. This review summarizes the current knowledge on the stress biology of Aspergillus species, illuminating what we have learned from the genomic data in this "post-genomic era." PMID- 27007957 TI - Community Paramedicine--Addressing Questions as Programs Expand. PMID- 27007958 TI - A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. AB - BACKGROUND: There is concern that antidiabetic incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues, can increase the risk of heart failure. Ongoing clinical trials may not have large enough samples to effectively address this issue. METHODS: We applied a common protocol in the analysis of multiple cohorts of patients with diabetes. We used health care data from four Canadian provinces, the United States, and the United Kingdom. With the use of a nested case-control analysis, we matched each patient who was hospitalized for heart failure with up to 20 controls from the same cohort; matching was based on sex, age, cohort-entry date, duration of treated diabetes, and follow-up time. Cohort-specific hazard ratios for hospitalization due to heart failure among patients receiving incretin-based drugs, as compared with those receiving oral antidiabetic-drug combinations, were estimated by means of conditional logistic regression and pooled across cohorts with the use of random-effects models. RESULTS: The cohorts included a total of 1,499,650 patients, with 29,741 hospitalized for heart failure (incidence rate, 9.2 events per 1000 persons per year). The rate of hospitalization for heart failure did not increase with the use of incretin-based drugs as compared with oral antidiabetic-drug combinations among patients with a history of heart failure (hazard ratio, 0.86; 95% confidence interval [CI], 0.62 to 1.19) or among those without a history of heart failure (hazard ratio, 0.82; 95% CI, 0.67 to 1.00). The results were similar for DPP-4 inhibitors and GLP-1 analogues. CONCLUSIONS: In this analysis of data from large cohorts of patients with diabetes, incretin-based drugs were not associated with an increased risk of hospitalization for heart failure, as compared with commonly used combinations of oral antidiabetic drugs. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT02456428.). PMID- 27007960 TI - CLINICAL PRACTICE. Chronic Stable Angina. PMID- 27007959 TI - Symptomatic Dengue in Children in 10 Asian and Latin American Countries. AB - BACKGROUND: The control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic. METHODS: We monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria. RESULTS: Approximately 10% of the febrile episodes in each cohort were confirmed to be VCD, with 319 VCD episodes (4.6 episodes per 100 person-years) occurring in the Asian cohort and 389 VCD episodes (2.9 episodes per 100 person-years) occurring in the Latin American cohort; no trend according to age group was observed. The incidence of dengue hemorrhagic fever was less than 0.3 episodes per 100 person-years in each cohort. The percentage of VCD episodes requiring hospitalization was 19.1% in the Asian cohort and 11.1% in the Latin American cohort. In comparable age groups (9 to 12 years and 13 to 16 years), the burden of dengue was higher in Asia than in Latin America. CONCLUSIONS: The burdens of dengue were substantial in the two regions and in all age groups. Burdens varied widely according to country, but the rates were generally higher and the disease more frequently severe in Asian countries than in Latin American countries. (Funded by Sanofi Pasteur; CYD14 and CYD15 ClinicalTrials.gov numbers, NCT01373281 and NCT01374516.). PMID- 27007961 TI - IMAGES IN CLINICAL MEDICINE. Diffuse Melanosis Cutis. PMID- 27007962 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 9-2016. A 29-Year-Old Man with Dyspnea and Chest Pain. PMID- 27007963 TI - Continuous or Interrupted Chest Compressions during CPR. PMID- 27007964 TI - Continuous or Interrupted Chest Compressions during CPR. PMID- 27007965 TI - Continuous or Interrupted Chest Compressions during CPR. PMID- 27007966 TI - Continuous or Interrupted Chest Compressions during CPR. PMID- 27007967 TI - Continuous or Interrupted Chest Compressions during CPR. PMID- 27007968 TI - Continuous or Interrupted Chest Compressions during CPR. PMID- 27007969 TI - Continuous or Interrupted Chest Compressions during CPR. PMID- 27007970 TI - Targeted Therapy Alone for Acute Promyelocytic Leukemia. PMID- 27007971 TI - IMAGES IN CLINICAL MEDICINE. Tracheobronchomegaly. PMID- 27007972 TI - CT pulmonary angiography: simultaneous low-pitch dual-source acquisition mode with 70 kVp and 40 ml of contrast medium and comparison with high-pitch spiral dual-source acquisition with automated tube potential selection. AB - OBJECTIVE: To assess the feasibility of a 70-kVp CT pulmonary angiography (CTPA) protocol using simultaneous dual-source (SimDS) acquisition mode with 40 ml of contrast medium (CM) and comparison with a high-pitch spiral dual-source (SpiralDS) acquisition protocol with automated tube potential selection (ATPS). METHODS: Following the introduction of a new 70-kVp/40-ml SimDS-CTPA protocol in December 2014 for all patients with a body mass index (BMI) below 35 kg m(-2), the first 35 patients were retrospectively included in this study and assigned to Group A (BMI: 27 +/- 4 kg m(-2), age: 66 +/- 15 years). The last 35 patients with a BMI below 35 kg m(-2) who had received SpiralDS-CTPA with ATPS were included for comparison (Group B) (70 ml CM; BMI: 27 +/- 4 kg m(-2), age: 68 +/- 16 years). Subjective image quality (image quality) was assessed by two radiologists (from 1, non-diagnostic, to 4, excellent). Signal-to-noise ratio (SNR), contrast to-noise ratio (CNR), volumetric CT dose index (CTDIvol), dose-length product (DLP) and effective dose were assessed. RESULTS: All examinations were of diagnostic image quality. Subjective image quality, SNR and CNR were comparable between Groups A and B (3.7 +/- 0.6 vs 3.7 +/- 0.5, 14.6 +/- 6.0 vs 13.9 +/- 3.7 and 12.4 +/- 5.7 vs 11.6 +/- 3.3, respectively; p > 0.05). CTDIvol, DLP and effective dose were significantly lower in Group A than in Group B (4.5 +/- 1.6 vs 7.5 +/- 2.1 mGy, 143.3 +/- 44.8 vs 278.3 +/- 79.44 mGy cm and 2.0 +/- 0.6 vs 3.9 +/- 1.1 mSv, respectively; p < 0.05). CONCLUSION: 70-kVp SimDS-CTPA with 40 ml of CM is feasible and provides diagnostic image quality, while radiation dose and CM can be reduced by almost 50% and 40%, respectively, compared with a SpiralDS-CTPA protocol with ATPS. ADVANCES IN KNOWLEDGE: 70-kVp SimDS-CTPA with 40 ml of CM is feasible in patients with a BMI up to 35 kg m(-2) and can help reduce radiation exposure and CM in these patients. PMID- 27007973 TI - Agricultural Management and Climatic Change Are the Major Drivers of Biodiversity Change in the UK. AB - Action to reduce anthropogenic impact on the environment and species within it will be most effective when targeted towards activities that have the greatest impact on biodiversity. To do this effectively we need to better understand the relative importance of different activities and how they drive changes in species' populations. Here, we present a novel, flexible framework that reviews evidence for the relative importance of these drivers of change and uses it to explain recent alterations in species' populations. We review drivers of change across four hundred species sampled from a broad range of taxonomic groups in the UK. We found that species' population change (~1970-2012) has been most strongly impacted by intensive management of agricultural land and by climatic change. The impact of the former was primarily deleterious, whereas the impact of climatic change to date has been more mixed. Findings were similar across the three major taxonomic groups assessed (insects, vascular plants and vertebrates). In general, the way a habitat was managed had a greater impact than changes in its extent, which accords with the relatively small changes in the areas occupied by different habitats during our study period, compared to substantial changes in habitat management. Of the drivers classified as conservation measures, low intensity management of agricultural land and habitat creation had the greatest impact. Our framework could be used to assess the relative importance of drivers at a range of scales to better inform our policy and management decisions. Furthermore, by scoring the quality of evidence, this framework helps us identify research gaps and needs. PMID- 27007974 TI - A Novel Sample Processing Method for Rapid Detection of Tuberculosis in the Stool of Pediatric Patients Using the Xpert MTB/RIF Assay. AB - BACKGROUND: Tuberculosis (TB) is difficult to diagnose in children using molecular tests, because children have difficulty providing respiratory samples. Stool could replace sputum for diagnostic TB testing if adequate sample processing techniques were available. METHODS: We developed a rapid method to process large volumes of stool for downstream testing by the Xpert MTB/RIF (Xpert) TB-detection assay. The method was tested and optimized on stool samples spiked with known numbers of M. tuberculosis colony forming units (CFU), and stools from M. tuberculosis-infected cynomolgus macaques (Macaca fascicularis). Performance was scored on number of positive Xpert tests, the cycle thresholds (Cts) of the Xpert sample-processing control (SPC), and the Cts of the M. tuberculosis-specific rpoB probes. The method was then validated on 20 confirmed TB cases and 20 controls in Durban, South Africa. RESULTS: The assay's analytical limit of detection was 1,000 CFU/g of stool. As much as one gram of spiked stool could be tested without showing increased PCR inhibition. In analytical spiking experiments using human stool, 1g samples provided the best sensitivity compared to smaller amounts of sample. However, in Macaques with TB, 0.6g stool samples performed better than either 0.2g or 1.2g samples. Testing the stool of pediatric TB suspects and controls suggested an assay sensitivity of 85% (95% CI 0.6-0.9) and 84% (95% CI 0.6-0.96) for 0.6g and 1.2g stool samples, respectively, and a specificity of 100% (95% CI 0.77-1) and 94% (95% CI 0.7-0.99), respectively. CONCLUSION: This novel approach may permit simple and rapid detection of TB using pediatric stool samples. PMID- 27007975 TI - Comparative Effectiveness of Smoking Cessation Medications to Attenuate Weight Gain Following Cessation. AB - OBJECTIVE: To compare the postcessation weight gain following the use of different FDA-approved smoking cessation medications among obese smokers. METHODS: A retrospective cohort study was conducted using the General Electric (GE) electronic medical record database (2006-2011). The cohort consisted of obese adult smokers newly initiating use of an FDA-approved smoking cessation medication (i.e., bupropion vs. varenicline). The outcome variable was weight change at 3, 6, or 12 months following the first prescription. Descriptive analyses and t-tests were conducted to assess the frequency distribution of sample characteristics and their association with the postcessation weight change. Multivariate linear regression models were carried out to compare the weight change among the FDA-approved smoking cessation medications and to identify predictors of weight change at 3, 6, and 12 months after assessing the model assumptions. RESULTS: The mean weight gain was 1.14 pounds (+/-17.26), 2.06 pounds (+/-18.46), and 3.06 pounds (+/-20.78) at 3-, 6-, and 12-month, respectively. Obese smokers who were prescribed varenicline had a mean weight gain of 1.18 pounds (+/-16.75), 2.14 pounds (+/-18.14), and 3.12 pounds (+/ 20.89) for each follow up, while those who were prescribed bupropion had a mean weight gain of 0.23 pounds (+/-25.90), 0.22 pounds (+/-25.32), and 1.47 pounds (+/-17.50), respectively. Descriptive analysis showed that obese smokers taking bupropion had less weight gain than those taking varenicline at each follow up; however, this association was not statistically significant after accounting for all covariates. CONCLUSIONS: While patients using bupropion gained slightly less weight compared to those using varenicline, type of smoking cessation medication was not a significant predictor of weight change in the multivariate linear regression model. PMID- 27007976 TI - Association between S100B Levels and Long-Term Outcome after Aneurysmal Subarachnoid Hemorrhage: Systematic Review and Pooled Analysis. AB - S100 calcium binding protein B (S100B), a well-studied marker for neurologic injury, has been suggested as a candidate for predicting outcome after subarachnoid hemorrhage. We performed a pooled analysis summarizing the associations between S100B protein in serum and cerebrospinal fluid (CSF) with radiographic vasospasm, delayed ischemic neurologic deficit (DIND), delayed cerebral infarction, and Glasgow Outcome Scale (GOS) outcome. A literature search using PubMed, the Cochrane Library, and the EMBASE databases was performed to identify relevant studies published up to May 2015. The weighted Stouffer's Z method was used to perform a pooled analysis of outcome measures with greater than three studies. A total of 13 studies were included in this review. Higher serum S100B level was found to be associated with cerebral infarction as diagnosed by CT (padj = 3.1 x 10(-4)) and worse GOS outcome (padj = 5.5 x 10( 11)). There was no association found between serum and CSF S100B with radiographic vasospasm or DIND. S100B is a potential prognostic marker for aSAH outcome. PMID- 27007977 TI - Applications of Deep Learning in Biomedicine. AB - Increases in throughput and installed base of biomedical research equipment led to a massive accumulation of -omics data known to be highly variable, high dimensional, and sourced from multiple often incompatible data platforms. While this data may be useful for biomarker identification and drug discovery, the bulk of it remains underutilized. Deep neural networks (DNNs) are efficient algorithms based on the use of compositional layers of neurons, with advantages well matched to the challenges -omics data presents. While achieving state-of-the-art results and even surpassing human accuracy in many challenging tasks, the adoption of deep learning in biomedicine has been comparatively slow. Here, we discuss key features of deep learning that may give this approach an edge over other machine learning methods. We then consider limitations and review a number of applications of deep learning in biomedical studies demonstrating proof of concept and practical utility. PMID- 27007978 TI - Catalytic Mechanism of Nitrile Hydratase Subsequent to Cyclic Intermediate Formation: A QM/MM Study. AB - The catalytic mechanism of an Fe-containing nitrile hydratase (NHase) subsequent to the formation of a cyclic intermediate was investigated using a hybrid quantum mechanics/molecular mechanics (QM/MM) method. We identified the following mechanism: (i) proton transfer from betaTyr72 to the substrate via alphaSer113, and cleavage of the S-O bond of alphaCys114-SO(-) and formation of a disulfide bond between alphaCys109 and alphaCys114; (ii) direct attack of a water molecule on the sulfur atom of alphaCys114, which resulted in the generation of both an imidic acid and a renewed sulfenic cysteine; and (iii) isomerization of the imidic acid to the amide. In addition, to clarify the role of betaArg56K, which is one of the essential amino residues in the enzyme, we analyzed a betaR56K mutant in which betaArg56 was replaced by Lys. The results suggest that betaArg56 is necessary for the formation of disulfide intermediate by stabilizing the cleavage of the S-O bond via a hydrogen bond with the oxygen atom of alphaCys114 SO(-). PMID- 27007979 TI - Differential Regulation of TLR Signaling on the Induction of Antiviral Interferons in Human Intestinal Epithelial Cells Infected with Enterovirus 71. AB - Enterovirus 71 (EV71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. Few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to EV71 in the gut. We reported a robust induction of interferons (IFNs) in human intestinal epithelial cells (HT-29), which was suppressed in other types such as RD and HeLa cells. The underlying mechanism for the apparent difference remains obscure. In this study we report that in EV71-infected HT-29 cells, TLR/TRIF signaling was essential to IFN induction; viral replication increased and the induction of IFN-alpha, -beta, -omega, -kappa, and -epsilon decreased markedly in TRIF-silenced HT-29 cells. Importantly, TRIF was degraded by viral 3Cpro in RD cells, but resisted cleavage, and IRF3 was activated and translocated into the nucleus in HT-29 cells. Taken together, our data suggest that IFNs were induced differentially in human HT-29 cells through an intact TLR/TRIF signaling, which differs from other cell types and may be implicated in viral pathogenesis in EV71 infection. PMID- 27007980 TI - Interfacial Engineering of Bimetallic Ag/Pt Nanoparticles on Reduced Graphene Oxide Matrix for Enhanced Antimicrobial Activity. AB - Environmental biofouling caused by the formation of biofilm has been one of the most urgent global concerns. Silver nanoparticles (NPs), owing to their wide spectrum antimicrobial property, have been widely explored to combat biofilm, but their extensive use has raised growing concern because they persist in the environment. Here we report a novel hybrid nanocomposite that imparts enhanced antimicrobial activity and low cytotoxicity yet with the advantage of reduced silver loading. The nanocomposite consists of Pt/Ag bimetallic NPs (BNPs) decorated on the porous reduced graphene oxide (rGO) nanosheets. We demonstrate that the enhanced antimicrobial property against Escherichia coli is ascribed to the intricate control of the interfaces between metal compositions, rGO matrix, and bacteria, where the BNPs lead to a rapid release of silver ions, and the trapping of bacteria by the porous rGO matrix further provides high concentration silver ion sites for efficient bacteria-bactericide interaction. We envision that our facile approach significantly expands the design space for the creation of silver-based antimicrobial materials to achieve a wide spectrum of functionalities. PMID- 27007981 TI - Normal cognitive outcome in a PEX6 deficient girl despite neonatal multisystem presentation. PMID- 27007982 TI - A WHO reference reagent to standardize haemagglutination testing for anti-A and anti-B in serum and plasma: international collaborative study to evaluate a candidate preparation. AB - BACKGROUND AND OBJECTIVES: The aim of the study was to evaluate a lyophilized serum preparation, 14/300, for its suitability to serve as a World Health Organization (WHO) Reference Reagent to standardize and control haemagglutination titrations for anti-A and anti-B in serum and plasma, in an international collaborative study. MATERIALS AND METHODS: Serum preparation 14/300 and two plasma-based reserve preparations, 14/304 (high titre anti-A) and 14/208 (high titre anti-B), were titrated by 24 laboratories in 13 countries using direct (DRT) and indirect (IAT) haemagglutination techniques. RESULTS: There was eightfold to 64-fold variation in reported titres per preparation and method across laboratories, that is, titres extended over 4-7 dilutions, although intralaboratory variability was generally good, with over 90% of replicate titres within a twofold range. There was a reduction in interlaboratory variability when titres of the reserve preparations were adjusted relative to those of the candidate Reference Reagent. CONCLUSION: The establishment of 14/300 as a WHO Reference Reagent for high titre anti-A and anti-B in serum, with nominal anti-A and anti-B titres of 128 for DRT, and nominal anti-A and anti-B titres of 256 for IAT, will facilitate global standardization of haemagglutination titrations for anti-A and anti-B in patient samples and blood components. PMID- 27007983 TI - Factors Contributing to Background Television Exposure in Low-Income Mexican American Preschoolers. AB - Objective Background television (TV) exposure is harmful to young children, yet few studies have focused on predictors of exposure. This study's objectives were to elucidate demographic, environmental, and behavioral correlates of background TV exposure in low-income Mexican-American preschoolers and to explore caregiver beliefs about the impact of such exposure. Methods A convenience sample of low income Mexican-American female primary caregivers of preschoolers (3-5 years old, n = 309), recruited in safety-net clinics, were surveyed by phone. Caregivers reported the frequency of their child's exposure to background TV and responded to questions on the home media environment, TV use, and whether they had thought about background TV exposure and its impact on their child. Results Background TV exposure was common; 43 % reported that their child was often, very often, or always exposed to background TV. More hours of TV viewing by the caregiver and greater frequency of TV viewing during meals were associated with an increased frequency of exposure to background TV. Only 49 % of participants had ever thought about the impact of background TV. Believing that background TV is not harmful was associated with higher levels of background TV exposure. Conclusions Findings suggest that background TV exposure is frequent and caregiver awareness of its potential impact is low in low-income Mexican-American families. Beliefs that background TV is not harmful may predict risk of exposure. Potential targets for interventions focused on reducing background TV exposure in this population include increasing caregiver awareness of the potential negative impact of such TV exposure. PMID- 27007984 TI - Small-for-Gestational-Age Births are Associated with Maternal Relationship Status: A Population-Wide Analysis. AB - Objectives To examine the association between maternal relationship status during pregnancy and infant birth outcomes. Methods Observational study of the National Longitudinal Survey of Youth 1979, a nationally representative sample of 12,686 men and women between the ages of 14 and 21. We used data from surveys of women reporting childbirth between 1979 and 2004. Relationship status was defined as relationship with an opposite-sex partner in the child's birth year. Relationship stability was defined as the consistency in relationship status in the 1 year before, of, and after the child's birth. Childbirth outcome included small-for gestational age (SGA) infant. We applied random effects logistic regression models to assess the association between relationship status and stability and childbirth outcome-adjusting for maternal race, infant sex, history of miscarriage, employment, maternal age, multiparity, cohort-entry year, household poverty status, and tobacco use. Results The study included 4439 women with 8348 live births. In fully adjusted models, term SGA infants were more commonly born to partnered women (AOR 1.81; 95 % CI 1.20-2.73) and unmarried women (AOR 1.82; CI 1.34-2.47; LRT p value 0.0001), compared to married women. SGA infants were also more commonly born in unstable relationships (AOR 1.72; 95 % CI 1.14-2.63; LRT p value 0.01) compared to stable relationships. Conclusions for Practice Maternal relationship status and stability during pregnancy is independently associated with risk of SGA infant birth. PMID- 27007985 TI - Fetal Deaths in Brazil: Historical Series Descriptive Analysis 1996-2012. AB - Objective We seek to comprehensively assess stillbirths in Brazil, to compare the Brazilian findings with global trends and to identify the limitations of the fetal death record system. Method We studied fetal deaths in Brazil between 1996 and 2012 within the following five regions of the country: the North, Northeast, Southeast, South, and Central-West, through an analysis of data obtained from the Unified Health System's (SUS) Informatics Department. The rates of stillbirth in Brazil and in these regions were calculated in relation to the maternal and gestational age and education, birth weight, type of pregnancy, delivery type, weight ranges and cause of death. Results There were 579,661 recorded fetal deaths and a decrease of 22.9 % in the stillbirth rate. In 2012, the overall rate was 10.0/1000 births; the North and Northeast regions had the highest rates (10.3 and 12.1, respectively) and the South region had the lowest rate (7.7/1000 births). Two-thirds of the deaths occurred in pregnancies of 28 or more weeks. Low education was an important risk factor, with rates of 24.3/1000 birth in women with no formal education and 4.7/1000 birth in women with 12 or more years of study in 2012. More than 40 % of the causes of deaths were nonspecific. Conclusions Despite the gradual decline in stillbirth rates, Brazil still has stillbirth rates that are nearly two times higher than those found in developed countries. There are inequalities between country regions portrayed by the significant variation in mortality rates specified by cause. PMID- 27007986 TI - Maternal Depression and Childhood Overweight in the CHAMACOS Study of Mexican American Children. AB - Objective Although previous studies have examined the impact of maternal depression on child overweight and obesity, little is known about the relationship in Latino families, who suffer from high risks of depression and obesity. We prospectively investigated the association between depressive symptoms in women with young children and child overweight and obesity (overweight/obesity) at age 7 years among Latino families. Methods Participants included 332 singletons with anthropometric measures obtained at 7 years from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort study. Maternal depression was assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale when the children were 1, 3.5, and 7 years. Overweight and obesity was measured by body mass index (kg/m(2)) at age 7 years. Results 63 % of women had CES-D scores consistent with depression in at least one of the 3 given assessments. Compared to children whose mothers were never depressed, children whose mothers were depressed at all three assessments had 2.4 times the adjusted odds of overweight/obesity at age 7 years (95 % CI 1.1 5.6). However, a single positive maternal depression screen was not associated with child overweight/obesity and there was no difference in the odds of overweight/obesity by the age of the child when maternal depression occurred. Conclusion Chronic maternal depression during a child's early life was associated with child overweight/obesity at 7 years. Addressing maternal depression is a critical component of comprehensive obesity prevention and treatment strategies for Latino children. PMID- 27007987 TI - Clinical application of PET/MRI in oncology. AB - Hybrid imaging with integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) combines the advantages of the high-resolution anatomic data from MRI and functional imaging data from PET, and has the potential to improve the diagnostic evaluation of various types of cancers. The clinical oncologic applications of this newest hybrid imaging technology are evolving and substantial efforts are underway to define the role of PET/MRI in routine clinical use. The current published literature suggests that PET/MRI may play an important role in the evaluation of patients with certain types of malignancies, involving anatomic locations such as the pelvis and the liver. The purpose of this article is to review the current published PET/MRI literature in specific body oncologic applications. In addition, PET/MRI protocols and some of the technical issues of this hybrid imaging will be briefly discussed. J. Magn. Reson. Imaging 2016;44:265-276. PMID- 27007988 TI - Behcet's Disease and Nervous System Involvement. AB - OPINION STATEMENT: Management of neuro-Behcet's disease can be divided into two stages: treatment of acute attacks and prevention of relapses. Treatment of acute attacks is accomplished by high-dose intravenous corticosteroids followed by maintenance treatment with oral steroids for 6-12 months depending on the type and severity of the neurological involvement. Relapses can be prevented by using immunosuppressants. Oral immunosuppressants such as azathioprine and mycophenolate are the most widely utilized agents for this purpose. Patients who are refractory or who cannot tolerate these medications can be managed by cyclophosphamide, interferon alpha, or anti-TNF-alpha monoclonal antibodies such as infliximab, etanercept, and adalimumab. Recent reports showed that newer agents such as tocilizumab, canakinumab, and anakinra, which exert their biological activity through IL-1 and IL-6 pathways, are also promising treatment alternatives for progressive or relapsing patients. PMID- 27007989 TI - Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients. AB - BACKGROUND: Fetuin-A is known as a circulating inhibitor of vascular calcification. Factors associated with serum fetuin-A concentrations after long term use of different phosphate binders in hemodialysis patients is still uncertain. METHODS: In the post-hoc study, we analyzed serum fetuin-A and biochemical factors (Ca, P, i-PTH, hsCRP, TG, LDL-C) in 50 hemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. 23 patients received sevelamer and 27 patients received calcium carbonate. RESULTS: After the 48-week treatment, the sevelamer group had less serum calcium increment, less iPTH decrement, more ALK-P increment, more hsCRP decrement and more LDL-C decrement. There was no significant difference in the serum fetuin-A decrement between two groups. Decreased serum fetuin-A levels were found after 48 week treatment in both groups: from 210.61 (104.73) to 153.85 (38.64) ug/dl, P = 0.003 in sevelamer group, from 203.95 (107.87) to 170.90 (58.02) ug/mL, P =0.002 in calcium group. The decrement in serum fetuin-A (Deltafetuin-A) levels was associated with DeltaCa (rho = - 0.230, P = 0.040), DeltaiPTH (rho = 0.306, P = 0.031) and Deltaalbumin (rho = 0.408, P = 0.003), not associated with sevelamer use, DeltaP and DeltahsCRP. CONCLUSION: After long-term sevelamer or calcium carbonate treatment, both groups of maintenance HD patients had lower serum fetuin-A levels. Serum levels of increased calcium, decreased iPTH and decreased albumin were associated with the serum fetuin-A decrement. PMID- 27007990 TI - Relative Strength at the Hip, Knee, and Ankle Is Lower Among Younger and Older Females Who Are Obese. AB - BACKGROUND AND PURPOSE: The mobility of individuals who are obese can be limited compared with their healthy weight counterparts. Lower limb strength has been associated with mobility, and reduced strength may contribute to mobility limitation among individuals who are obese. However, our understanding of the effects of obesity on lower limb strength is limited. The purpose of this study was to investigate the effects of obesity and age on extension and flexion strength at the hip, knee, and ankle. METHODS: Using a cross-sectional design, 10 younger (18-30 years) healthy weight (body mass index = 18-24.9 kg/m), 10 younger obese (body mass index >30 kg/m), 10 older (65-80 years) healthy weight, and 10 older obese female participants performed isokinetic maximum voluntary contractions in ankle plantar flexion (PF), ankle dorsiflexion (DF), knee extension (KE), knee flexion (KF), hip extension (HE), and hip flexion (HF). RESULTS AND DISCUSSION: Absolute strength among obese participants was 29% higher in DF (P = .002), 27% higher in KE (P = .004), and 23% higher in HF (P = .001), compared with healthy weight participants. Strength relative to body mass among obese participants was 31% lower in PF (P < .001), 14% lower in DF (P = .042), 16% lower in KE (P = .015), 27% lower in KF (P < .001), 29% lower in HE (P < .001), and 19% lower in HF (P = .001). CONCLUSIONS: Obese females exhibited lower relative strength at the ankle and hip, similar to the lower relative strength exhibited at the knee. Obese females also exhibited higher absolute strength, but only for 3 of 6 lower limb exertions investigated. This lack of uniformity across the 6 exertions is likely due to the still unclear underlying biomechanical mechanism responsible for these strength differences, which may also be influenced by aging. The effects of obesity on lower limb strength were also generally consistent between the 2 age groups investigated. PMID- 27007991 TI - Health Characteristics, Neuromuscular Attributes, and Mobility Among Primary Care Patients With Symptomatic Lumbar Spinal Stenosis: A Secondary Analysis. AB - BACKGROUND AND PURPOSE: Mobility problems are common among older adults. Symptomatic lumbar spinal stenosis (SLSS) is a major contributor to mobility limitations among older primary care patients. In comparison with older primary care patients with mobility problems but without SLSS, it is unclear how mobility problems differ in older primary care patients with SLSS. The purpose of this study was to compare health characteristics, neuromuscular attributes, and mobility status in a sample of older primary care patients with and without SLSS who were at risk for mobility decline. We hypothesized that patients with SLSS will manifest poorer health and greater severity of neuromuscular impairments and mobility limitations. METHODS: This is a secondary analysis of the Boston Rehabilitative Study of the Elderly (Boston RISE). Fifty community-dwelling primary care patients aged 65 years or older at risk for mobility decline met inclusion criteria. SLSS was determined on the basis of computerized tomography (CT) scan and self-reported symptoms characteristic of neurogenic claudication. Outcome measures included health characteristics, neuromuscular attributes (trunk endurance, limb strength, limb speed, limb strength asymmetry, ankle range of motion [ROM], knee ROM, kyphosis, sensory loss), and mobility (Late-Life Function and Disability Instrument: basic and advanced lower extremity function subscales, 400-meter walk test, habitual gait speed, and Short Physical Performance Battery score). Health characteristics were collected at a baseline assessment. Neuromuscular attributes and mobility status were measured at the annual visit closest to conducting the CT scan. RESULTS AND DISCUSSION: Five participants met criteria for having SLSS. Differences are reported in medians and interquartile ranges. Participants with SLSS reported more global pain, a greater number of comorbid conditions [SLSS: 7.0 (2.0) vs no-SLSS: 4.0 (2.0), P < .001], and experienced greater limitation in knee ROM [SLSS: 115.0 degrees (8.0 degrees ) vs no-SLSS: 126.0 degrees (10.0 degrees ), P = .04] and advanced lower extremity function than those without SLSS.A limitation of this study was its small sample size and therefore inability to detect potential differences across additional measures of neuromuscular attributes and mobility. Despite the limitation, the differences in mobility for participants with SLSS may support physical therapists in designing interventions for older adults with SLSS. Participants with SLSS manifested greater mobility limitations that exceeded meaningful thresholds across all performance-based and self-reported measures. In addition, our study identified that differences in mobility extended beyond not just walking capacity but also across a variety of tasks that make up mobility for those with and without SLSS. CONCLUSION: Among older primary care patients who are at risk for mobility decline, patients with SLSS had greater pain, higher levels of comorbidity, greater limitation in knee ROM, and greater limitations in mobility that surpassed meaningful thresholds. These findings can be useful when prioritizing interventions that target mobility for patients with SLSS. PMID- 27007992 TI - Amitorines A and B, Nitrogenous Diterpene Metabolites of Theonella swinhoei: Isolation, Structure Elucidation, and Asymmetric Synthesis. AB - Two new nitrogenous prenylbisabolanes never before found in Lithistid sponges have been isolated from Theonella swinhoei. These new diterpenes, named amitorine A (1) and amitorine B (2), containing a prenylbisabolane skeleton have been characterized by spectroscopic analyses, and the relative and absolute configurations of 1 and 2 were determined by asymmetric synthesis of both diastereomers via the common bicyclic lactone 6 intermediate. PMID- 27007993 TI - Erratum to: Evidence of selection signatures that shape the Persian cat breed. PMID- 27007994 TI - Lumbar intervertebral disc allograft transplantation: long-term mobility and impact on the adjacent segments. AB - PURPOSE: Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model. METHODS: Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb's method. The anatomy of the adjacent discs was observed histologically. RESULTS: DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved. CONCLUSIONS: Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months. PMID- 27007995 TI - Population pharmacokinetics of zonisamide after oral administration in healthy Chinese volunteers. AB - To develop a population-based pharmacokinetic model for the oral antiepileptic drug zonisamide using a cohort of healthy (nonepileptic) subjects and evaluate the effect of individual factors on the pharmacokinetics of zonisamide. 30 young adults (21-39 years) in good health were randomly assigned to 3 equal groups (1:1 sex ratio) for single-dose administration of zonisamide at 200 mg, 300 mg, or 400 mg. An additional 9 subjects (22-24 years) were administered once daily zonisamide at 300 mg for 14 days, and comprised the multiple dosing group. Venous blood samples were collected for analysis prior to (baseline, 0 hours) and after (1-300 hours) drug administration, providing 607 total samples used to build the pharmacokinetic model. The population pharmacokinetic analysis was performed by ICON's nonlinear mixed-effect modeling (NONMEM) software. Validation of the final model was carried out by nonparametric bootstrapping and visual predictive check. The zonisamide pharmacokinetics was best described by a two-compartment model with first-order elimination. In the final model, the estimated value of clearance (CL) was 23.25 L/h, the volume of distribution of the central compartment (Vc) was 34.50 L, the intercompartmental clearance (Q) was 20.22 L/h, and the Ka was 0.026 h(-1). The peripheral volume of distribution (Vp) was 1,429 L for single dose and 1,003 L for multiple doses. Body weight was the significant covariate affecting CL, Vc, Vp, and Q. Otherwise, female subjects had a lower Q than male subjects. The pharmacokinetics of zonisamide after oral administration could be described using a linear first-order elimination two-compartment model, which may provide a reference for clinical use of zonisamide in Chinese adults. PMID- 27007996 TI - Prescribed drugs and polypharmacy in healthcare service users in South Korea: an analysis based on National Health Insurance Claims data. AB - OBJECTIVE: This study was conducted to analyze and compare the exposure to individually prescribed drugs and the prevalence of polypharmacy according to age group and concomitant disease in South Korea. METHODS: The use of prescribed drugs was evaluated according to average numbers of prescription drugs used daily during a year or month, using the Korean Health Insurance Claims Database, which is representative of over 90% of citizens, in 2010 and 2011. The use of prescribed drugs was also analyzed according to concomitant diseases and age. Polypharmacy was defined as the use of 5 or more drugs daily during a specific observation period, and proportions of polypharmacy users were calculated according to comorbidity and age group. RESULTS: The annual average numbers of daily used prescription drugs in 2010 and 2011 were 0.3 (SD = 0.5), 0.4 (SD = 0.7), 1.2 (SD = 1.5), and 2.3 (SD = 2.0) for people aged < 20 years, 20-49 years, 50-64 years, and >= 65 years, respectively. Proportions of individuals demonstrating polypharmacy increased with age and were 9.5% and 44.1% for elderly individuals in the year- and month-based analyses, respectively. The annual average number of daily medications used increased by ~2 drugs in the concomitant disease group, and the higher mortality group used a higher number of prescribed drugs than the lower mortality group. CONCLUSIONS: The results highlight the elevated burden of multi-medication in elderly patients, and the study found that prescribed drug use increased with age and the number of concomitant diseases. PMID- 27007997 TI - Population pharmacokinetic-pharmacodynamic (PopPK/PD) modeling of risperidone and its active metabolite in Chinese schizophrenia patients. AB - PURPOSE: Risperidone is a second-generation antipsychotic agent commonly used in the treatment of ~ 31.1% of schizophrenia patients in China, it is the most commonly-prescribed antipsychotic agent. Despite the abundant use of risperidone, population pharmacokinetic-pharmacodynamic models of risperidone have not been performed in Chinese schizophrenia patients. The objective of this study was to develop a population pharmacokinetic-pharmacodynamic (PopPK/PD) model to describe the PK behavior and efficacy of risperidone and 9-hydroxy-risperidone (active metabolite) in Chinese patients. METHODS: Plasma concentration data (702 measurements from 131 patients) and positive and negative syndrome scale (PANSS) scores (258 observations from 56 patients) were analyzed using a nonlinear mixed effects modeling (NONMEM) approach with first-order conditional estimation with interaction (FOCEI). The influence of potential covariates was evaluated. Model robustness was assessed using external validation, normalized prediction distribution error, nonparametric bootstrap, and visual predictive check approaches. RESULTS: Risperidone concentration data were well described by a one compartmental model incorporating an additional compartment that refers to the concentration profiles of 9-hydroxy-risperidone. A complex absorption procedure was incorporated into the model to describe the metabolism of risperidone to 9 hydroxy-risperidone in the gastrointestinal (GI) tract. A binomial distribution in the estimated clearance (CL) of risperidone has been identified in our model. Decrease in PANSS score along with total AUC (AUCtotal) of risperidone and 9 hydroxy-risperidone was best characterized by an Emax model with 3 transit compartments describing the delay of drug effect. CONCLUSIONS: Considerable differences in PK behavior and drug effect of risperidone have been identified among Chinese extensive metabolizing (EM) and poor metabolizing (PM) patients. This PopPK/PD model may fulfill individualized treatment in clinical practice and may potentially be transferred to other antipsychotic therapies. PMID- 27007998 TI - Bioequivalence assessment of ambroxol orally-disintegrating tablet after a single oral-dose administration to healthy volunteers. AB - OBJECTIVE: In this study, a modified LC-MS/MS method was used to determine plasma ambroxol concentration and thereby examine the bioequivalence of two ambroxol medications among healthy Chinese male volunteers. METHODS: The study used a single-dose, randomized, open-label design principle and calculated pharmacokinetic parameters for the comparison of the two formulations. RESULTS: Administration of a single oral dose of either the test drug or reference drug was found to be safe in healthy subjects. No severe, serious, or life-threatening clinical or drug-related side effects were reported during the study. The majority of clinical laboratory test results were within the normal range or not clinically significant. The pharmacokinetic parameters for ambroxol oral tablets and ambroxol orally disintegrating tablets were comparable. For the comparison of the two formulations, the 90% confidence intervals for the log-transformed pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-inf) fell within the bioequivalence< acceptance criteria (80-125%). CONCLUSIONS: The ambroxol oral tablets were bioequivalent to ambroxol orally-disintegrating tablets in healthy human adult male volunteers, under fasting conditions. PMID- 27007999 TI - Relative bioavailability between two teriparatide formulations in healthy volunteers. AB - OBJECTIVE: To compare the pharmacokinetics, relative bioavailability (RB), immunogenicity, and safety after a single dose of test or reference formulation of teriparatide in healthy human volunteers in order to demonstrate whether both products are similar. RESEARCH DESIGN AND METHODS: We compared pharmacokinetic parameters, immunogenicity, and safety after a single dose of two formulations (Osteofortil(r) and Forteo(r)) of teriparatide in a randomizedsequence, open label, two-period crossover study in 24 healthy volunteers. The washout period between formulations was 7 days. Blood samples were collected at baseline and 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, 90, 120, 150 minutes, and 3 and 4 hours after administration. Teriparatide concentrations were determined using ELISA. Adverse events were monitored. RESULTS: Geometric mean (90% CI) Cmax for test and reference formulations were 165.86 (153.35 - 212.13) and 175.37 (164.04 - 221.04) pg/mL, the AUC0-t was 14,932 (5,275 - 15,752) and 14,153 (1,861 - 16,875) pg*min/mL, and the AUC0-infinity was 16,147 (15,047 - 18,799) and 15,467 (14,473 18,126) pg*min/mL, respectively. The test/reference ratios (90% CI) for Cmax, AUC0-t, and AUC0-infinity were 94.58% (85.29 - 104.87), 105.5% (97.77 - 113.84), and 104.4% (96.97 - 112.39), respectively No subject reported adverse events. CONCLUSION: Test formulation met pharmacokinetic criteria for bioequivalence. PMID- 27008000 TI - The role of 18F-FDG PET/CT in infectious endocarditis: a systematic review and meta-analysis. AB - PURPOSE: To systematically review and conduct a meta-analysis of the available evidence for PET/CT using 18F-fluorodeoxyglucose as tracers in the imaging of infectious endocarditis (IE). METHODS: Databases, including PubMed, Embase, and Web of Science, were searched for studies that examined the diagnostic value of 18F-FDG PET/CT for patients with IE. The reference lists following review articles and those of the included articles were checked to complement the electronic searches. The data extraction and methodological quality assessment were completed by two independent reviewers, and the meta-analysis was then conducted using Meta-Disc software, version 1.4. RESULTS: A total of 6 studies involving 246 patients was included. The results of the meta-analysis indicated that the pooled sensitivity was 61% (95% confidence interval (CI), 52-88%), and the pooled specificity was 88% (95% CI, 80-93%). The positive likelihood ratio was 3.24 (95% CI, 1.67-6.28, p = 0.224), and the negative likelihood ratio was 0.50 (95% CI, 0.32-0.77, p = 0.015). The diagnostic odds ratio was 6.98 (95% CI, 2.55-19.10, p = 0.145), the overall area under the curve (AUC) was 0.8230 (SE = 0.1085), and the Q* value was 0.7563 (SE = 0.0979). CONCLUSIONS: 18F-FDG PET/CT is currently not sufficient for the diagnosis of IE because of its low sensitivity. However, 18F-FDG PET/CT might be a useful tool for the diagnosis of skin and pocket cardiovascular implantable electronic device (CIED) infections and prosthetic valve endocarditis (PVE). PMID- 27008001 TI - Association of TNFSF4 (rs3850641) gene polymorphisms and coronary heart disease: an evidence-based meta-analysis. AB - OBJECTIVE: To clarify the effects of TNFSF4 (rs3850641) polymorphisms on coronary heart disease (CHD) risk. METHOD: Published literature from Pubmed, Embase, ISI Wed of Knowledge, Cochrane Library, and Chinese databases were retrieved. All studies evaluating the association between TNFSF4 (rs3850641) polymorphisms and CHD risk were included. Summary odds ratios (ORs) and 95% confidence intervals (CI) were calculated employing random-effects models irrespective of between study heterogeneity. RESULTS: A total of 9 eligible studies was included in this meta-analysis. Overall analysis showed that the rs3850641 G allele was not associated with CHD, compared with the A allele, with OR of 1.10 (95% CI, 0.96 1.27; p = 0.174). Genotypic analysis showed that there was no significant association between the GG, GA, GG + GA, and CHD, compared with participants with AA, with ORs of 1.23 (95% CI, 0.75-2.03; p = 0.409), 1.04 (95% CI, 0.84-1.29; p = 0.705), and 1.07 (95% CI, 0.85-1.34; p = 0.589), respectively. On the other hand, in the subgroup analysis by ethnicity, source of controls, genotyping methods, or matching criteria, there was still no statistically significant association between TNFSF4 (rs3850641) polymorphisms and CHD risk. CONCLUSIONS: This meta analysis reveals that TNFSF4 (rs3850641) polymorphisms is not associated with CHD risk. PMID- 27008002 TI - Persistence with antidepressant drugs in patients with dementia: a retrospective database analysis. AB - BACKGROUND: The aims of the present study are to determine what proportion of patients with dementia receives antidepressants, how long the treatment is administered, and what factors increase the risk of discontinuation. METHODS: The study was based on Disease Analyzer database and included 1,203 general practitioners (GP) and 209 neurologists/psychiatrists (NP). 12,281 patients with a diagnosis of dementia and an initial prescription of an antidepressant drug between January 2004 and December 2013 were included. The main outcome measure was antidepressant discontinuation rates within 6 months of the index date. RESULTS: After 6 months of follow-up, 52.7% of dementia patients treated with antidepressants had stopped medication intake. There was a significantly decreased risk for treatment discontinuation for patients using selective serotonin reuptake inhibitors (SSRRIs) or serotonin and norepinephrine reuptake inhibitors (SSNRIs) compared to tricyclic antidepressants. There was a significantly increased risk of treatment discontinuation for older patients and patients treated in NP practice. Comorbidity of diabetes or history of stroke was associated with a decreased risk of treatment discontinuation. CONCLUSION: The study results show insufficient persistence in antidepressant treatment in dementia patients in a real world setting. The improvement must be achieved to ensure the treatment recommended in the guidelines. PMID- 27008003 TI - Nitro-redox reactions at a frustrated borane/phosphane Lewis pair. AB - The unsaturated 1,4-P/B-FLPs reduced nitrobenzene to nitrosobenzene which was directly trapped by an allylboration reaction to give the seven-membered B-O-P compounds and . The FLP reacted analogously with trans-beta-nitrostyrene. The products were characterized by X-ray diffraction. PMID- 27008004 TI - Neuronal Differentiation of Induced Pluripotent Stem Cells on Surfactant Templated Chitosan Hydrogels. AB - The development of effective tissue engineering materials requires careful consideration of several properties beyond biocompatibility, including permeability and mechanical stiffness. While surfactant templating has been used for over a decade to control the physical properties of photopolymer materials, the potential benefit of this technique with regard to biomaterials has yet to be fully explored. Herein we demonstrate that surfactant templating can be used to tune the water uptake and compressive modulus of photo-cross-linked chitosan hydrogels. Interestingly, templating with quaternary ammonium surfactants also hedges against property fluctuations that occur with changing pH. Further, we demonstrate that, after adequate surfactant removal, these materials are nontoxic, support the attachment of induced pluripotent stem cells and facilitate stem cell differentiation to neuronal phenotypes. These results demonstrate the utility of surfactant templating for optimizing the properties of biomaterials intended for a variety of applications, including retinal regeneration. PMID- 27008005 TI - The predictive role of ADC values in prostate cancer patients treated with carbon ion radiotherapy: initial clinical experience at Shanghai Proton and Heavy Ion Center (SPHIC). AB - OBJECTIVE: The aim of our study was to investigate the predictive role of apparent diffusion coefficient (ADC) values in evaluating for therapeutic changes from carbon-ion radiotherapy (CIRT) in prostate cancer patients. MATERIALS AND METHODS: Thirty-one patients with prostate cancer treated with CIRT were enrolled in this retrospective study. Diffusion-weighted imaging (DWI) at 3-T was performed before and after CIRT. Before and after treatment, ADC values were measured in the tumors and in the benign tissues of the prostate, and serum prostate-specific antigen (PSA) levels were also assessed. We divided the patients into two groups: PSA response (PSA declines >=50 %) and non-PSA response group (PSA declines <50 %). RESULTS: After CIRT treatment, the mean ADC value of the tumors (1.23 * 10(-3)mm(2)/s) was significantly increased as compared with the pretreatment value (1.07 * 10(-3)mm(2)/s) (p < 0.001), whereas the ADC values of the benign tissues after treatment did not significantly increase compared with the pretreatment values (p = 0.235). The mean PSA level was significantly reduced from 2.027 ng/mL before treatment to 0.822 ng/mL, respectively, after treatment (p = 0.0063). The mean of ADC changes in PSA response group before and after CIRT was significantly higher than that in non-PSA response group (?ADC value: 0.217 vs 0.097 * 10(-3)mm(2)/s, p = 0.0229), and the rate of patients with PSA response was higher in the high ?ADC group (?ADC >= 0.10) than in the low ?ADC group (?ADC < 0.10) (72.7 and 33.3 %, respectively), but marginally significant (p = 0.056). Additionally, the baseline tumor ADC values revealed a negative correlation with changes in PSA levels after treatment (correlation coefficient, rho = -0.524; p = 0.0025). CONCLUSION: Our preliminary results suggest that ADC vales measurement may be a useful imaging biomarker for prediction and early assessment of therapeutic response of prostate cancer to CIRT. PMID- 27008007 TI - Overview of Sequence Data Formats. AB - Next-generation sequencing experiment can generate billions of short reads for each sample and processing of the raw reads will add more information. Various file formats have been introduced/developed in order to store and manipulate this information. This chapter presents an overview of the file formats including FASTQ, FASTA, SAM/BAM, GFF/GTF, BED, and VCF that are commonly used in analysis of next-generation sequencing data. PMID- 27008006 TI - Her2-neu score as a prognostic factor for outcome in patients with triple negative breast cancer. AB - PURPOSE: Triple-negative breast cancer (TNBC) is characterized by a strong heterogeneity with regard to tumour biology as well as in the clinical course of the disease. This study aimed to analyse whether there are any prognostic factors enabling prediction of the clinical outcome in patients with TNBC. Particularly, the impact of Her2-neu score 0 versus Her2-neu score 1 and 2 on survival was investigated. MATERIALS AND METHODS: We retrospectively studied a cohort of 1013 patients with TNBC, diagnosed at seven hospitals between May 2002 and February 2015. We studied the impact of Her2-neu scores (0 vs. 1 or 2 with negative FISH) on disease-free survival (DFS) and overall survival (OS). RESULTS: 1013 patients were included in this study. 447 (44.13 %) of them had a T2-4 tumour. A total of 314 (31.00 %) were nodal-positive and 714 (70.48 %) had high-grade tumours. The Her2-neu score of all participating patients was determined. 588 (58.05 %) of them had a Her2-neu score 0, and 425 (41.95 %) had a score of 1 or 2. This study shows that TNBC patients with a Her2-neu score 0 had a significantly poorer outcome regarding DFS (p = 0.0001) and OS (p = 0.0051) compared to a score of 1 or 2. In contrast, grading did not seem to have any prognostic value for women with TNBC. CONCLUSION: The Her2-neu score 0 might be considered as an innovative prognostic factor for patients with TNBC indicating poor clinical outcome. PMID- 27008008 TI - Integrative Exploratory Analysis of Two or More Genomic Datasets. AB - Exploratory analysis is an essential step in the analysis of high throughput data. Multivariate approaches such as correspondence analysis (CA), principal component analysis, and multidimensional scaling are widely used in the exploratory analysis of single dataset. Modern biological studies often assay multiple types of biological molecules (e.g., mRNA, protein, phosphoproteins) on a same set of biological samples, thereby creating multiple different types of omics data or multiassay data. Integrative exploratory analysis of these multiple omics data is required to leverage the potential of multiple omics studies. In this chapter, we describe the application of co-inertia analysis (CIA; for analyzing two datasets) and multiple co-inertia analysis (MCIA; for three or more datasets) to address this problem. These methods are powerful yet simple multivariate approaches that represent samples using a lower number of variables, allowing a more easily identification of the correlated structure in and between multiple high dimensional datasets. Graphical representations can be employed to this purpose. In addition, the methods simultaneously project samples and variables (genes, proteins) onto the same lower dimensional space, so the most variant variables from each dataset can be selected and associated with samples, which can be further used to facilitate biological interpretation and pathway analysis. We applied CIA to explore the concordance between mRNA and protein expression in a panel of 60 tumor cell lines from the National Cancer Institute. In the same 60 cell lines, we used MCIA to perform a cross-platform comparison of mRNA gene expression profiles obtained on four different microarray platforms. Last, as an example of integrative analysis of multiassay or multi-omics data we analyzed transcriptomic, proteomic, and phosphoproteomic data from pluripotent (iPS) and embryonic stem (ES) cell lines. PMID- 27008009 TI - Study Design for Sequencing Studies. AB - Once a biochemical method has been devised to sample RNA or DNA of interest, sequencing can be used to identify the sampled molecules with high fidelity and low bias. High-throughput sequencing has therefore become the primary data acquisition method for many genomics studies and is being used more and more to address molecular biology questions. By applying principles of statistical experimental design, sequencing experiments can be made more sensitive to the effects under study as well as more biologically sound, hence more replicable. PMID- 27008010 TI - Genomic Annotation Resources in R/Bioconductor. AB - Annotation resources make up a significant proportion of the Bioconductor project (Huber et al., Nat Methods 12:115-121, 2015). And there are also a diverse set of online resources available which are accessed using specific packages. Here we describe the most popular of these resources and give some high level examples on how to use them. PMID- 27008011 TI - The Gene Expression Omnibus Database. AB - The Gene Expression Omnibus (GEO) database is an international public repository that archives and freely distributes high-throughput gene expression and other functional genomics data sets. Created in 2000 as a worldwide resource for gene expression studies, GEO has evolved with rapidly changing technologies and now accepts high-throughput data for many other data applications, including those that examine genome methylation, chromatin structure, and genome-protein interactions. GEO supports community-derived reporting standards that specify provision of several critical study elements including raw data, processed data, and descriptive metadata. The database not only provides access to data for tens of thousands of studies, but also offers various Web-based tools and strategies that enable users to locate data relevant to their specific interests, as well as to visualize and analyze the data. This chapter includes detailed descriptions of methods to query and download GEO data and use the analysis and visualization tools. The GEO homepage is at http://www.ncbi.nlm.nih.gov/geo/. PMID- 27008012 TI - A Practical Guide to The Cancer Genome Atlas (TCGA). AB - The Cancer Genome Atlas (TCGA) is one of the most ambitious and successful cancer genomics programs to date. The TCGA program has generated, analyzed, and made available genomic sequence, expression, methylation, and copy number variation data on over 11,000 individuals who represent over 30 different types of cancer. This chapter provides a brief overview of the TCGA program and detailed instructions and tips for investigators on how to find, access, and download this data. PMID- 27008013 TI - Working with Oligonucleotide Arrays. AB - Preprocessing microarray data consists of a number of statistical procedures that convert the observed intensities into quantities that represent biological events of interest, like gene expression and allele-specific abundances. Here, we present a summary of the theory behind microarray data preprocessing for expression, whole transcriptome and SNP designs and focus on the computational protocol used to obtain processed data that will be used on downstream analyses. We describe the main features of the oligo Bioconductor package, an application designed to support oligonucleotide microarrays using the R statistical environment and the infrastructure provided by Bioconductor, allowing the researcher to handle probe-level data and interface with advanced statistical tools under a simplified framework. We demonstrate the use of the package by preprocessing data originated from three different designs. PMID- 27008014 TI - Meta-Analysis in Gene Expression Studies. AB - This chapter introduces methods to synthesize experimental results from independent high-throughput genomic experiments, with a focus on adaptation of traditional methods from systematic review of clinical trials and epidemiological studies. First, it reviews methods for identifying, acquiring, and preparing individual patient data for meta-analysis. It then reviews methodology for synthesizing results across studies and assessing heterogeneity, first through outlining of methods and then through a step-by-step case study in identifying genes associated with survival in high-grade serous ovarian cancer. PMID- 27008015 TI - Practical Analysis of Genome Contact Interaction Experiments. AB - The three dimensional (3D) architecture of chromosomes is not random but instead tightly organized due to chromatin folding and chromatin interactions between genomically distant loci. By bringing genomically distant functional elements such as enhancers and promoters into close proximity, these interactions play a key role in regulating gene expression. Some of these interactions are dynamic, that is, they differ between cell types, conditions and can be induced by specific stimuli or differentiation events. Other interactions are more structural and stable, that is they are constitutionally present across several cell types. Genome contact interactions can occur via recruitment and physical interaction between chromatin-binding proteins and correlate with epigenetic marks such as histone modifications. Absence of a contact can occur due to presence of insulators, that is, chromatin-bound complexes that physically separate genomic loci. Understanding which contacts occur or do not occur in a given cell type is important since it can help explain how genes are regulated and which functional elements are involved in such regulation. The analysis of genome contact interactions has been greatly facilitated by the relatively recent development of chromosome conformation capture (3C). In an even more recent development, 3C was combined with next generation sequencing and led to Hi-C, a technique that in theory queries all possible pairwise interactions both within the same chromosome (intra) and between chromosomes (inter). Hi-C has now been used to study genome contact interactions in several human and mouse cell types as well as in animal models such as Drosophila and yeast. While it is fair to say that Hi-C has revolutionized the study of chromatin interactions, the computational analysis of Hi-C data is extremely challenging due to the presence of biases, artifacts, random polymer ligation and the huge number of potential pairwise interactions. In this chapter, we outline a strategy for analysis of genome contact experiments based on Hi-C using R and Bioconductor. PMID- 27008016 TI - Quantitative Comparison of Large-Scale DNA Enrichment Sequencing Data. AB - DNA enrichment followed by sequencing (DNA-IP seq) is a versatile tool in molecular biology with a wide variety of applications. Computational analysis of differential DNA enrichment between conditions is important for identifying epigenetic alterations in disease compared to healthy controls and for revealing dynamic epigenetic modifications throughout normal and distorted cell differentiation and development. We present a protocol for genome-wide comparative analysis of DNA-IP sequencing data to identify statistically significant differential sequencing coverage between two conditions by considering variation across replicates. The protocol provides a detailed description for the comparative analysis of DNA-IP sequencing data including basic data processing, quality controls, and identification of differential enrichment using the Bioconductor package "MEDIPS". PMID- 27008017 TI - Variant Calling From Next Generation Sequence Data. AB - The use of next generation nucleotide sequencing to discover and genotype small sequence variants has led to numerous insights into the molecular causes of various diseases. This chapter describes the use of freely available software to align next generation sequencing reads to a reference and then to use the resulting alignments to call, annotate, view, and filter small sequence variants. The suggested variant calling workflow includes read alignment with novoalign, the removal of polymerase chain reaction duplicate sequences with samtools or bamUtils, and the detection of variants with Freebayes or bam2mpg software. ANNOVAR is then used to annotate the predicted variants using gene models, population frequencies, and predicted mutation severity, producing variant files which can be viewed and filtered with the variant display tool VarSifter. PMID- 27008019 TI - NGS-QC Generator: A Quality Control System for ChIP-Seq and Related Deep Sequencing-Generated Datasets. AB - The combination of massive parallel sequencing with a variety of modern DNA/RNA enrichment technologies provides means for interrogating functional protein genome interactions (ChIP-seq), genome-wide transcriptional activity (RNA-seq; GRO-seq), chromatin accessibility (DNase-seq, FAIRE-seq, MNase-seq), and more recently the three-dimensional organization of chromatin (Hi-C, ChIA-PET). In systems biology-based approaches several of these readouts are generally cumulated with the aim of describing living systems through a reconstitution of the genome-regulatory functions. However, an issue that is often underestimated is that conclusions drawn from such multidimensional analyses of NGS-derived datasets critically depend on the quality of the compared datasets. To address this problem, we have developed the NGS-QC Generator, a quality control system that infers quality descriptors for any kind of ChIP-sequencing and related datasets. In this chapter we provide a detailed protocol for (1) assessing quality descriptors with the NGS-QC Generator; (2) to interpret the generated reports; and (3) to explore the database of QC indicators (www.ngs-qc.org) for >21,000 publicly available datasets. PMID- 27008018 TI - Genome-Scale Analysis of Cell-Specific Regulatory Codes Using Nuclear Enzymes. AB - High-throughput sequencing technologies have made it possible for biologists to generate genome-wide profiles of chromatin features at the nucleotide resolution. Enzymes such as nucleases or transposes have been instrumental as a chromatin probing agent due to their ability to target accessible chromatin for cleavage or insertion. On the scale of a few hundred base pairs, preferential action of the nuclear enzymes on accessible chromatin allows mapping of cell state-specific accessibility in vivo. Such accessible regions contain functionally important regulatory sites, including promoters and enhancers, which undergo active remodeling for cells adapting in a dynamic environment. DNase-seq and the more recent ATAC-seq are two assays that are gaining popularity. Deep sequencing of DNA libraries from these assays, termed genomic footprinting, has been proposed to enable the comprehensive construction of protein occupancy profiles over the genome at the nucleotide level. Recent studies have discovered limitations of genomic footprinting which reduce the scope of detectable proteins. In addition, the identification of putative factors that bind to the observed footprints remains challenging. Despite these caveats, the methodology still presents significant advantages over alternative techniques such as ChIP-seq or FAIRE-seq. Here we describe computational approaches and tools for analysis of chromatin accessibility and genomic footprinting. Proper experimental design and assay specific data analysis ensure the detection sensitivity and maximize retrievable information. The enzyme-based chromatin profiling approaches represent a powerful and evolving methodology which facilitates our understanding of how the genome is regulated. PMID- 27008020 TI - Operating on Genomic Ranges Using BEDOPS. AB - The bulk of modern genomics research includes, in part, analyses of large data sets, such as those derived from high resolution, high-throughput experiments, that make computations challenging. The BEDOPS toolkit offers a broad spectrum of fundamental analysis capabilities to query, operate on, and compare quantitatively genomic data sets of any size and number. The toolkit facilitates the construction of complex analysis pipelines that remain efficient in both memory and time by chaining together combinations of its complementary components. The principal utilities accept raw or compressed data in a flexible format, and they provide built-in features to expedite parallel computations. PMID- 27008021 TI - GMAP and GSNAP for Genomic Sequence Alignment: Enhancements to Speed, Accuracy, and Functionality. AB - The programs GMAP and GSNAP, for aligning RNA-Seq and DNA-Seq datasets to genomes, have evolved along with advances in biological methodology to handle longer reads, larger volumes of data, and new types of biological assays. The genomic representation has been improved to include linear genomes that can compare sequences using single-instruction multiple-data (SIMD) instructions, compressed genomic hash tables with fast access using SIMD instructions, handling of large genomes with more than four billion bp, and enhanced suffix arrays (ESAs) with novel data structures for fast access. Improvements to the algorithms have included a greedy match-and-extend algorithm using suffix arrays, segment chaining using genomic hash tables, diagonalization using segmental hash tables, and nucleotide-level dynamic programming procedures that use SIMD instructions and eliminate the need for F-loop calculations. Enhancements to the functionality of the programs include standardization of indel positions, handling of ambiguous splicing, clipping and merging of overlapping paired-end reads, and alignments to circular chromosomes and alternate scaffolds. The programs have been adapted for use in pipelines by integrating their usage into R/Bioconductor packages such as gmapR and HTSeqGenie, and these pipelines have facilitated the discovery of numerous biological phenomena. PMID- 27008022 TI - Visualizing Genomic Data Using Gviz and Bioconductor. AB - The Gviz package offers a flexible framework to visualize genomic data in the context of a variety of different genome annotation features. Being tightly embedded in the Bioconductor genomics landscape, it nicely integrates with the existing infrastructure, but also provides direct data retrieval from external sources like Ensembl and UCSC and supports most of the commonly used annotation file types. Through carefully chosen default settings the package greatly facilitates the production of publication-ready figures of genomic loci, while still maintaining high flexibility due to its ample customization options. PMID- 27008023 TI - Introducing Machine Learning Concepts with WEKA. AB - This chapter presents an introduction to data mining with machine learning. It gives an overview of various types of machine learning, along with some examples. It explains how to download, install, and run the WEKA data mining toolkit on a simple data set, then proceeds to explain how one might approach a bioinformatics problem. Finally, it includes a brief summary of machine learning algorithms for other types of data mining problems, and provides suggestions about where to find additional information. PMID- 27008024 TI - Experimental Design and Power Calculation for RNA-seq Experiments. AB - Power calculation is a critical component of RNA-seq experimental design. The flexibility of RNA-seq experiment and the wide dynamic range of transcription it measures make it an attractive technology for whole transcriptome analysis. These features, in addition to the high dimensionality of RNA-seq data, bring complexity in experimental design, making an analytical power calculation no longer realistic. In this chapter we review the major factors that influence the statistical power of detecting differential expression, and give examples of power assessment using the R package PROPER. PMID- 27008025 TI - It's DE-licious: A Recipe for Differential Expression Analyses of RNA-seq Experiments Using Quasi-Likelihood Methods in edgeR. AB - RNA sequencing (RNA-seq) is widely used to profile transcriptional activity in biological systems. Here we present an analysis pipeline for differential expression analysis of RNA-seq experiments using the Rsubread and edgeR software packages. The basic pipeline includes read alignment and counting, filtering and normalization, modelling of biological variability and hypothesis testing. For hypothesis testing, we describe particularly the quasi-likelihood features of edgeR. Some more advanced downstream analysis steps are also covered, including complex comparisons, gene ontology enrichment analyses and gene set testing. The code required to run each step is described, along with an outline of the underlying theory. The chapter includes a case study in which the pipeline is used to study the expression profiles of mammary gland cells in virgin, pregnant and lactating mice. PMID- 27008026 TI - Position open on ESPR board. PMID- 27008027 TI - Construction and characterization of gelonin and saporin plasmids for toxic gene based cancer therapy. AB - Toxic gene therapy (or suicidal gene therapy) is gaining enormous interest, specifically for the treatment of cancer. The success of this therapy lies in several crucial factors, including the potency of gene products to kill the transfected tumor cells and the transfection ability of the transfection vehicles. To address the potency problem, in the present study, we engineered two separate mammalian transfection plasmids (pSAP and pGEL) containing genes encoding ribosome inactivating proteins (RIPs), gelonin and saporin. After the successful preparation and amplification of the plasmids, they were tested on various cancer cell lines (HeLa, U87, 9L, and MDA-MB-435) and a noncancerous cell line (293 HEK) using polyethyleneimine (PEI) as the transfection agent. Transfection studies performed under varying gene concentration, incubation time, and gene-to-PEI ratios revealed that, compared to the treatment of pGFP (GFP expression plasmid)/PEI, both pGEL/PEI and pSAP/PEI complexes could induce significantly augmented cytotoxic effects at only 2 MUg/mL gene concentration. Importantly, these cytotoxic effects were observed universally in all tested cancer cell lines. Overall, this study demonstrated the potential of pGEL and pSAP as effective gene candidates for the toxic gene-based cancer therapy. PMID- 27008028 TI - Improving health care systems by building 'more Europe'. PMID- 27008030 TI - Aligning physical learning spaces with the curriculum: AMEE Guide No. 107. AB - This Guide explores emerging issues on the alignment of learning spaces with the changing curriculum in medical education. As technology and new teaching methods have altered the nature of learning in medical education, it is necessary to re think how physical learning spaces are aligned with the curriculum. The better alignment of learning spaces with the curriculum depends on more directly engaged leadership from faculty and the community of medical education for briefing the requirements for the design of all kinds of learning spaces. However, there is a lack of precedent and well-established processes as to how new kinds of learning spaces should be programmed. Such programmes are essential aspects of optimizing the intended experience of the curriculum. Faculty and the learning community need better tools and instruments to support their leadership role in briefing and programming. A Guide to critical concepts for exploring the alignment of curriculum and learning spaces is provided. The idea of a networked learning landscape is introduced as a way of assessing and evaluating the alignment of physical spaces to the emerging curriculum. The concept is used to explore how technology has widened the range of spaces and places in which learning happens as well as enabling new styles of learning. The networked learning landscaped is explored through four different scales within which learning is accommodated: the classroom, the building, the campus, and the city. High-level guidance on the process of briefing for the networked learning landscape is provided, to take into account the wider scale of learning spaces and the impact of technology. Key to a successful measurement process is argued to be the involvement of relevant academic stakeholders who can identify the strategic direction and purpose for the design of the learning environments in relation to the emerging demands of the curriculum. PMID- 27008029 TI - Primary health care utilisation and its costs among middle-aged smokers. AB - OBJECTIVE: To study and compare the utilisation of primary health care services among 46-year-old current smokers, ex-smokers and never-smokers, and to estimate the corresponding costs. METHODS: This population-based cohort study is based on the Northern Finland Birth Cohort 1966, which is a longitudinal research program in Finland's two northernmost provinces. The study is based on data collected at the 46-year follow-up, during which a total of 4997 individuals completed questionnaires on their primary health care service utilisation. Primary health care covered visits to both occupational and public health care (typically community health centres). RESULTS: Current smokers visited primary health care professionals more often per year than never-smokers, regardless of gender (RR 1.24, 95 % confidence interval 1.10-1.43 for men; RR 1.10, 1.01-1.22 for women). When primary health care services were categorised based on the type of service provided, current smokers of both genders were more likely to visit a dentist (RR 1.56, 1.32-1.84 for men; RR 1.34, 1.15-1.55 for women) or a physician (RR 1.20, 1. 03-1.40 for men; RR 1.15, 1.02-1.30 for women) than their never-smoking counterparts (BMI adjusted for). For men, the total annual costs of primary health care visits were 28 % higher for current smokers versus never-smokers (P < 0.001). For women, the difference was 21 % (P < 0.01). CONCLUSIONS: Smokers visit primary health care professionals more often already at the age of 46, before the expected diagnosis of fatal smoking-related illnesses. This phenomenon not only predicts an elevated incidence of serious illnesses in later life (such as cardiovascular disease), but also causes an economic burden on the health care system. PMID- 27008031 TI - Natalizumab in relapsing-remitting multiple sclerosis. AB - Natalizumab is the first humanized moclonal antibody indicated in the treatment of relapsing-remitting multiple sclerosis (RRMS). Based on its remarkable efficacy in reducing disease activity and reducing the risk of disability progession in RRMS, and the risk of a serious adverse event (progressive multifocal leukoencephalopathy [PML]), natalizumab was indicated in active RRMS, mostly as a second-line therapy. With natalizumab and other recent anti inflammatory therapies, the concept of no evidence of disease activity has emerged and may sometimes be achievable. Use of natalizumab in other inflammatory diseases of the nervous system has been less encouraging than in MS. PML remains the main serious adverse event occuring during natalizumab therapy. PML risk stratification according to JCV serology and JCV index is now being applied more often. Other PML risk biomarkers are being evaluated. If stopping natalizumab is planned, the wash-out period needs to be less than 12 weeks and probably closer to 4-8 weeks with efficient validated immunomodulatory or immunosuppressive therapies in RRMS. PMID- 27008032 TI - Intracellularly Biodegradable Polyelectrolyte/Silica Composite Microcapsules as Carriers for Small Molecules. AB - Microcapsules that can be efficiently loaded with small molecules and effectively released at the target area through the degradation of the capsule shells hold great potential for treating diseases. Traditional biodegradable polyelectrolyte (PE) capsules can be degraded by cells and eliminated from the body but fail to encapsulate drugs with small molecular weight. Here, we report a poly-l-arginine hydrochloride (PARG)/dextran sulfate sodium salt (DEXS)/silica (SiO2) composite capsule that can be destructed in cells and of which the in situ formed inorganic SiO2 enables loading of small model molecules, Rhodamine B (Rh-B). The composite capsules were fabricated based on the layer-by-layer (LbL) technique and the hydrolysis of tetraethoxysilane (TEOS). Capsules composed of nondegradable PEs and SiO2, polyllamine hydrochloride (PAH)/poly(sodium 4-styrenesulfonate) (PSS)/silica (the control sample), were prepared and briefly compared with the degradable composite capsules. An intracellular degradation study of both types of composite capsules revealed that PARG/DEXS/silica capsules were degraded into fragments and lead to the release of model molecules in a relatively short time (2 h), while the structure of PAH/PSS/silica capsules remained intact even after 3 days incubation with B50 cells. Such results indicated that the polymer components played a significant role in the degradability of the SiO2. Specifically, PAH/PSS scaffolds blocked the degradation of SiO2. For PARG/DEXS/silica capsules, we proposed the effects of both hydrolytic degradation of amorphous silica and enzymatic degradation of PARG/DEXS polymers as a cell degradation mechanism. All the results demonstrated a new type of functional composite microcapsule with low permeability, good biocompatibility, and biodegradability for potential medical applications. PMID- 27008033 TI - Bilateral Superior Labial Mucosal Transposition Flaps to Correct Stenosis of the Nares Following Bilateral Rostral Maxillectomy Combined with Nasal Planum Resection in a Dog. AB - OBJECTIVE: To describe a technique using labial mucosal flaps to correct stenosis of the nares subsequent to bilateral rostral maxillectomy and nasal planum resection. STUDY DESIGN: Case report ANIMALS: Client-owned dog. METHODS: A 10 year-old, neutered male Golden Retriever developed repeated stenosis of the nares, at first after bilateral rostral maxillectomy and nasal planum resection, and again after revision surgery. Bilateral, superior labial mucosal transposition flaps were created and interpolated between the nasal mucosa and skin after debridement of scar tissue. RESULTS: The stenosis did not recur after mucosal flap transposition and the dog returned to normal quality of life (last follow-up 25 months postoperative). CONCLUSION: Single-stage, superior labial mucosal transposition flaps can be used to correct nares stenosis subsequent to previous surgery. PMID- 27008034 TI - A scaffoldless technique for self-generation of three-dimensional keratinospheroids on liquid crystal surfaces. AB - We describe a new scaffold-free three-dimensional (3D) cell culture model using cholesteryl ester based lyotropic liquid crystal (LC) substrates. Keratinocytes were deposited randomly on the LC surface where they self-assembled into 3D microtissues or keratinospheroids. The cell density required to form spheroids was optimized. We investigated cell viability using dead/live cell assays. The adhesion characteristics of cells within the microtissues were determined using histological sectioning and immunofluorescence staining. Fourier transform infrared spectroscopy (FTIR) was used to characterize the biochemistry of the keratinospheroids. We found that both cells and microtissues could migrate on the LC surface. The viability study indicated approximately 80% viability of cells in the microtissues up to 20 days of culture. Strong intercellular adhesion was observed in the stratification of the multi-layered microspheroids using field emission-scanning electron microscopy (FE-SEM) and histochemical staining. The cytoskeleton and vinculins of the cells in the microtissues were expressed diffusely, but the microtissues were enriched with lipids and nucleic acids, which indicates close resemblance to the conditions in vivo. The basic 3D culture model based on LC may be used for cell and microtissue migration studies in response to cytochemical treatment. PMID- 27008035 TI - Fall-related experiences of stroke survivors: a meta-ethnography. AB - PURPOSE: Health professionals view falls after stroke as common adverse events with both physical and psychological consequences. Stroke survivors' experiences are less well understood. The aim of this systematic review was to explore the perception of falls-risk within the stroke recovery experience from the perspective of people with stroke. METHODS: A systematic literature search was conducted. Papers that used qualitative methods to explore the experiences of individuals with stroke around falls, falls-risk and fear of falling were included. Two reviewers independently assessed the methodological quality of papers. Meta-ethnography was conducted. Concepts from each study were translated into each other to form theories that were combined through a "lines-of-argument" synthesis. RESULTS: Four themes emerged from the six included qualitative studies: (i) Fall circumstances, (ii) perception of fall consequences, (iii) barriers to community participation and (iv) coping strategies. The synthesis revealed that stroke survivors' perceived consequences of falls exist on a continuum. Cognitive and emotional adjustment may be required in the successful adoption of coping strategies to overcome fall-related barriers to participation. CONCLUSIONS: Stroke survivors' fall-related experiences appear to exist within the context of activity and community participation. Further research is warranted due to the small number of substantive studies available for synthesis. Implications for Rehabilitation Health care professionals should recognize that cognitive and emotional adjustment may berequired for stroke survivors to accept strategies for overcoming falls-risk, including dependenceon carers and assistive devices. Several factors in addition to physical interventions may be needed to minimize falls-risk whileincreasing activity participation. These factors could include increasing public awareness about the effects of stroke and falls risk,and ensuring access to psychological services for stroke survivors. Rehabilitation professionals should reflect on whether they perceive there to be an appropriatelevel of fear of falling post-stroke. They should understand that stroke survivors might not conceptualize falls-risk in this way. PMID- 27008036 TI - Chronic Obstructive Pulmonary Disease Is Not Associated with KRAS Mutations in Non-Small Cell Lung Cancer. AB - Mutations in epithelial growth factor receptor (EGFR), as well as in the EGFR downstream target KRAS are frequently observed in non-small cell lung cancer (NSCLC). Chronic obstructive pulmonary disease (COPD), an independent risk factor for developing NSCLC, is associated with an increased activation of EGFR. In this study we determined presence of EGFR and KRAS hotspot mutations in 325 consecutive NSCLC patients subjected to EGFR and KRAS mutation analysis in the diagnostic setting and for whom the pulmonary function has been determined at time of NSCLC diagnosis. Information about age at diagnosis, sex, smoking status, forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) was collected. Chronic obstructive pulmonary disease(COPD) was defined according to 2013 GOLD criteria. Chi-Square, student t-test and multivariate logistic regression were used to analyze the data. A total of 325 NSCLC patients were included, 193 with COPD and 132 without COPD. COPD was not associated with presence of KRAS hotspot mutations, while EGFR mutations were significantly higher in non-COPD NSCLC patients. Both female gender (HR 2.61; 95% CI: 1.56 4.39; p<0.001) and smoking (HR 4.10; 95% CI: 1.14-14.79; p = 0.03) were associated with KRAS mutational status. In contrast, only smoking (HR 0.11; 95% CI: 0.04-0.32; p<0.001) was inversely associated with EGFR mutational status. Smoking related G>T and G>C transversions were significantly more frequent in females (86.2%) than in males (61.5%) (p = 0.008). The exon 19del mutation was more frequent in non-smokers (90%) compared to current or past smokers (36.8%). In conclusion, KRAS mutations are more common in females and smokers, but are not associated with COPD-status in NSCLC patients. EGFR mutations are more common in non-smoking NSCLC patients. PMID- 27008037 TI - A Perspective on Opioid Pharmacotherapy: Where We Are and How We Got Here. AB - Four decades of concerted pharmacotherapy research has netted us three medications approved for the treatment of opioid addiction. The clinical pharmacology, safety, efficacy, and clinical use of these medications are familiar to most clinical researchers and clinicians in addiction medicine. Less common is an understanding of the social and political forces behind the choice of these particular agents for their development and how these forces continue to influence how clinicians interact with patients who have opioid use disorder. This review brings into focus those forces and puts into context how we came to have these particular medications. What we know determines our views of the world we live in, including our patients and ourselves, as well as those to whom we give power to govern us. The issues are raised by the author, who does not provide resolutions; answers to the questions of how to address the issues must come from the reader. PMID- 27008038 TI - Formation of Prussian-Blue-Analog Nanocages via a Direct Etching Method and their Conversion into Ni-Co-Mixed Oxide for Enhanced Oxygen Evolution. AB - Novel Ni-Co-Prussian-blue-analog nano-cages consisting of pyramid-like walls were prepared via a facile chemical etching process with ammonia at room temperature. After annealing in air, the derived Ni-Co mixed oxide nanocages exhibit enhanced electrocatalytic activity and excellent stability toward the oxygen-evolution reaction. PMID- 27008039 TI - Use of Menopausal Hormone Therapy and Bioidentical Hormone Therapy in Australian Women 50 to 69 Years of Age: Results from a National, Cross-Sectional Study. AB - Menopausal Hormone Therapy (MHT) use in Australia fell by 55% from 2001 to 2005, following the release of large-scale findings on its risks and benefits. Comprehensive national data, including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004-5 National Health Survey, when 11% of women aged 45+ years were estimated to be current MHT users. No national data are available on prevalence of use of "bioidentical" hormone therapy (BHT). The objective of this study was to determine recent prevalence of MHT and BHT use. A cross-sectional, national, age-stratified, population survey was conducted in 2013. Eligible women, aged 50 69 years, resident in Australia were randomly sampled in 5-year age groups from the Medicare enrolment database (Australia's universal health scheme). The response rate was 22% based on return of completed questionnaires, and analyses were restricted to 4,389 women within the specified age range. The estimated population-weighted prevalence of current use of MHT was 13% (95%CI 12-14), which was broadly similar to the previously reported national figures in 2004-5, suggesting that the use of MHT in Australia has largely stabilised over the past decade. A total of 39% and 20% of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT, respectively, whereas 77% of hysterectomised current-users used oestrogen-only MHT. Almost three quarters of current-users [population-weighted prevalence 9% (95%CI 8-10)] had used MHT for >=5 years. In regard to BHT, estimated population-weighted prevalence of ever use was 6% (95%CI 6-7) and 2% (95%CI 2-3) for current use. The population-weighted prevalence of MHT and BHT combined, in current users in their fifties and sixties was 15% (95%CI 14-16). These data provide a recent national "snapshot" of Australian women's use of both conventional MHT and of BHT. PMID- 27008040 TI - A framework for organ dose estimation in x-ray angiography and interventional radiology based on dose-related data in DICOM structured reports. AB - Although interventional x-ray angiography (XA) procedures involve relatively high radiation doses that can lead to deterministic tissue reactions in addition to stochastic effects, convenient and accurate estimation of absorbed organ doses has traditionally been out of reach. This has mainly been due to the absence of practical means to access dose-related data that describe the physical context of the numerous exposures during an XA procedure. The present work provides a comprehensive and general framework for the determination of absorbed organ dose, based on non-proprietary access to dose-related data by utilizing widely available DICOM radiation dose structured reports. The framework comprises a straightforward calculation workflow to determine the incident kerma and reconstruction of the geometrical relation between the projected x-ray beam and the patient's anatomy. The latter is difficult in practice, as the position of the patient on the table top is unknown. A novel patient-specific approach for reconstruction of the patient position on the table is presented. The proposed approach was evaluated for 150 patients by comparing the estimated position of the primary irradiated organs (the target organs) with their position in clinical DICOM images. The approach is shown to locate the target organ position with a mean (max) deviation of 1.3 (4.3), 1.8 (3.6) and 1.4 (2.9) cm for neurovascular, adult and paediatric cardiovascular procedures, respectively. To illustrate the utility of the framework for systematic and automated organ dose estimation in routine clinical practice, a prototype implementation of the framework with Monte Carlo simulations is included. PMID- 27008041 TI - Nonprobative photos rapidly lead people to believe claims about their own (and other people's) pasts. AB - Photos lead people to believe that both true and false events have happened to them, even when those photos provide no evidence that the events occurred. Research has shown that these nonprobative photos increase false beliefs when combined with misleading suggestions and repeated exposure to the photo or target event. We propose that photos exert similar effects without those factors, and test that proposition in five experiments. In Experiment 1, people saw the names of several animals and pretended to give food to or take food from each. Then people saw the animal names again, half with a photo of the animal and half alone, and decided whether they had an experience with each. The photos led people to believe they had experiences with the animals. Moreover, Experiments 2 5 provided evidence that photos exerted these effects by making it easier to bring related thoughts and images to mind-a feeling that people mistook as evidence of genuine experience. In each experiment, photos led people to believe positive claims about the past (but not negative claims), consistent with evidence that feelings of ease selectively increase positive judgments. Experiment 4 also showed that photos (like other manipulations of ease) bias people's judgments broadly, producing false beliefs about other people's pasts. Finally, in Experiment 5, photos exerted more powerful effects when they depicted unfamiliar animals, and thus could most help bring information to mind. These findings suggest that nonprobative photos can distort the past without other factors that encourage false beliefs, and that they operate by helping related thoughts and images come to mind. PMID- 27008042 TI - Membrane-permeable Triphosphate Prodrugs of Nucleoside Analogues. AB - The metabolic conversion of nucleoside analogues into their triphosphates often proceeds insufficiently. Rate-limitations can be at the mono-, but also at the di and triphosphorylation steps. We developed a nucleoside triphosphate (NTP) delivery system (TriPPPro-approach). In this approach, NTPs are masked by two bioreversible units at the gamma-phosphate. Using a procedure involving H phosphonate chemistry, a series of derivatives bearing approved, as well as potentially antivirally active, nucleoside analogues was synthesized. The enzyme triggered delivery of NTPs was demonstrated by pig liver esterase, in human T lymphocyte cell extracts and by a polymerase chain reaction using a prodrug of thymidine triphosphate. The TriPPPro-compounds of some HIV-inactive nucleoside analogues showed marked anti-HIV activity. For cellular uptake studies, a fluorescent TriPPPro-compound was prepared that delivered the triphosphorylated metabolite to intact CEM cells. PMID- 27008043 TI - Ugly but tasty: A systematic review of possible human and animal health risks related to entomophagy. AB - BACKGROUND: According to many recent studies, the use of insects as food seems to be convenient, sustainable, economical and healthy. The objective of this study is to analyze the possible effects of insect consumption on human and animal health. METHODS: A systematic review of the literature was performed using the PubMed, Scopus and CAB databases. RESULTS: Of the 6026 items initially retrieved, 70 were eligible for inclusion; 40 studies analyzed the use of insects in human foods or drugs, while 30 analyzed the use of insects in animal feed. In humans, the most commonly analyzed risks are nutrient malabsorption, growth alteration, chemical and microbiological contamination and allergy risk. Studies of animals focus on growth alteration, nutrient malabsorption and hematic and qualitative meat alteration. CONCLUSION: In recent years, researchers have shifted their focus from the possible use of edible insects in animal feed to their use as possible nutrient sources for humans. The results suggest that, if properly treated and preserved, products derived from insects are safe and efficient sources of nutrients for animals. Further studies are needed to evaluate the possible effects of prolonged insect consumption on human health. PMID- 27008046 TI - Moving change-of-shift report to the bedside for UAP. PMID- 27008047 TI - Eight remediation strategies to improve test performance. PMID- 27008048 TI - Intentional foreign body ingestion: What do we know and how can we help? PMID- 27008052 TI - Nursing and the importance of body language. PMID- 27008053 TI - Lessons from Aristotle All things in moderation. PMID- 27008054 TI - Does your professional image need a makeover? PMID- 27008055 TI - Productive errors Transforming learning experiences in healthcare. PMID- 27008056 TI - Using bispectral index monitoring to gauge depth of sedation/analgesia. PMID- 27008057 TI - Bourbon virus: A novel pathogen. PMID- 27008058 TI - The urgent need for innovation in I.V. infusion devices. PMID- 27008060 TI - A Policy-Driven Perspective on Rising Drug Costs in Dermatology. PMID- 27008061 TI - Radical Prostatectomy at a 'High-Volume Centre': The Limitations of Patient Reported Outcome. PMID- 27008062 TI - Resectoscopic myomectomy. AB - Hysteroscopic myomectomy currently is the "gold standard" procedure for treating submucous myoma and represents an effective and safe solution to abnormal uterine bleeding and infertility myoma-related. Several studied have shown that, in the case of submucous myomas, resectoscopic myomectomy has several advantages compared with the traditional surgical treatment of myomectomy by laparotomy, in terms of reduced myometrial trauma, shorter hospitalization times and decreased risk of postoperative adhesion formation. The aim of this paper was to describe the alternative techniques, currently available, of resectoscopic myomectomy. The choice of the procedure mostly depends on the intramural extension of the myoma, as well as on personal experience and available equipment. PMID- 27008063 TI - Tetrabromobisphenol-A/S and Nine Novel Analogs in Biological Samples from the Chinese Bohai Sea: Implications for Trophic Transfer. AB - Tetrabromobisphenol-A/S (TBBPA/S) analogs have raised substantial concern because of their adverse effects and potential bioaccumulative properties, such as TBBPA bis(allyl ether) (TBBPA-BAE) and TBBPA bis(2,3-dibromopropyl ether) (TBBPA BDBPE). In this study, a comprehensive method for simultaneous determination of TBBPA/S and nine novel analogs, including TBBPA-BAE, TBBPA-BDBPE, TBBPS-BDBPE, TBBPA mono(allyl ether) (TBBPA-MAE), TBBPA mono(2-bromoallyl ether) (TBBPA-MBAE), TBBPA mono(2,3-dibromopropyl ether) (TBBPA-MDBPE), TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE in biological samples was developed. The distribution patterns and trophic transfer properties of TBBPA/S and analogs in various biological samples collected from the Chinese Bohai Sea were then studied in detail. For the first time, TBBPA-MBAE and TBBPS-BDBPE were detected in biological samples and TBBPA MBAE was identified as a byproduct. The concentrations of TBBPA and analogs ranged from ND (not detected or below the method detection limit) to 2782.8 ng/g lipid weight (lw), and for TBBPS and analogs ranged from ND to 927.8 ng/g lw. High detection frequencies (>86%) for TBBPA, TBBPS and TBBPA-MAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS-MBAE, and TBBPS-MDBPE were obtained. Meanwhile, TBBPA, TBBPS, and these five analogs displayed trophic dilution tendencies due to significantly negative correlations between trophic levels and lipid-corrected concentrations together with the trophic magnification factors (from 0.31 to 0.55). The results also indicated the novel TBBPA-MAE, TBBPA-MBAE, TBBPA-MDBPE, TBBPS-MAE, TBBPS MBAE, and TBBPS-MDBPE could be generated not only as byproducts, but also as the probable transformation products of commercial TBBPA/S derivatives. PMID- 27008064 TI - Erratum to: Evaluation of chemical castration with calcium chloride versus surgical castration in donkeys: testosterone as an endpoint marker. PMID- 27008065 TI - Myocardial injury after noncardiac surgery: an underappreciated problem and current challenges. AB - PURPOSE OF REVIEW: To review myocardial injury after noncardiac surgery (MINS), focusing on recent studies, including data on high-sensitivity troponin, which is likely to alter our understanding of MINS. RECENT FINDINGS: MINS is greatly underappreciated by clinicians, possibly because of its silent presentation. However, MINS is both common and clinically important. In total, 8% of at-risk patients will suffer a MINS, an event that is associated with death within 30 days with an odds ratio of 3.87 (95% CI 2.96-5.08). Most patients suffering MINS do not fulfill the criteria for perioperative myocardial infarction as they are asymptomatic. Consequently, postoperative troponin measurement is imperative for MINS detection. Evidence from randomized trials on how to prevent or how to treat MINS is still lacking. SUMMARY: Currently, we are limited to appreciating the vast extent of the MINS problem and applying recommendations based on observational data or derived from the nonoperative setting. Routine troponin measurements after noncardiac surgery and the increasing use of high-sensitivity troponins have revealed the larger underwater iceberg of perioperative myocardial injury and ischemia. Clinicians should be sensitized for this important complication and search for it using a perioperative troponin screening. PMID- 27008066 TI - Anesthetic considerations for pediatric obesity and adolescent bariatric surgery. AB - PURPOSE OF REVIEW: Pediatric obesity has become commonplace in our clinical practice, and presents anesthesia providers with numerous challenges. This study provides an up-to-date review of their perioperative care, including the measurement of pediatric obesity, rational drug dosing in obese children, and recent data on bariatric outcomes in adolescents. RECENT FINDINGS: Pediatric obesity is associated with a number of relevant comorbidities that impact anesthesia care, and specific children are at particularly high risk. Drug dosing remains problematic in this patient population, and recent evidence regarding appropriate drug administration is presented. Bariatric surgery in adolescents has shifted away from the roux-en-Y towards sleeve gastrectomy, with comparable results. SUMMARY: Safe and effective care of obese children demands careful perioperative management. High risk children are particularly vulnerable, and demand special attention. Bariatric surgery is an effective intervention for adolescents with severe obesity. PMID- 27008067 TI - Towards system-wide implementation of the International Classification of Functioning, Disability and Health (ICF) in routine practice: Developing simple, intuitive descriptions of ICF categories in the ICF Generic and Rehabilitation Set. AB - OBJECTIVE: A national, multi-phase, consensus process to develop simple, intuitive descriptions of International Classification of Functioning, Disability and Health (ICF) categories contained in the ICF Generic and Rehabilitation Sets, with the aim of enhancing the utility of the ICF in routine clinical practice, is presented in this study. METHODS: A multi-stage, national, consensus process was conducted. The consensus process involved 3 expert groups and consisted of a preparatory phase, a consensus conference with consecutive working groups and 3 voting rounds (votes A, B and C), followed by an implementation phase. In the consensus conference, participants first voted on whether they agreed that an initially developed proposal for simple, intuitive descriptions of an ICF category was in fact simple and intuitive. RESULTS: The consensus conference was held in August 2014 in mainland China. Twenty-one people with a background in physical medicine and rehabilitation participated in the consensus process. Four ICF categories achieved consensus in vote A, 16 in vote B, and 8 in vote C. DISCUSSION: This process can be seen as part of a larger effort towards the system-wide implementation of the ICF in routine clinical and rehabilitation practice to allow for the regular and comprehensive evaluation of health outcomes most relevant for the monitoring of quality of care. PMID- 27008068 TI - Satisfaction and attrition in paediatric weight management. AB - Paediatric obesity treatment experiences unacceptably high rates of attrition. Few studies have explored parent and child perspectives on dropout. This study sought to capture child and parent experience in treatment and expressed contributors to attrition. Children and parents enrolled in a single family-based weight management programme participated in semi-structured interviews, conducted either upon completion of the first intensive phase of treatment or program dropout. Interviews were recorded, transcribed and coded using a multistage inductive approach. Interviews were obtained from 57 parents and 30 children, nearly equal between 'completers' or 'dropouts'. Five themes emerged: overall positive experience with programme; logistical challenges of participation; improved health; discrepancies between child and parent experience and perception, and importance of structure and expectations of weight loss. Primary reasons given for dropout were time commitment; distance from clinic; missed school and work; lack of dedicated adolescent programme; clinic hours; and stress. Few parents or children expressed dissatisfaction. Children reportedly enjoyed 'having someone to talk to' about weight, and spending increased time with family. Children and parents overall reported positive experiences in this weight management programme. Attrition appears more related to logistical issues than low satisfaction. Innovative approaches to help overcome logistical challenges and preserve positive aspects may help in decreasing programme attrition. PMID- 27008069 TI - Treatment satisfaction with different weight loss methods among respondents with obesity. AB - Satisfaction with weight loss (WL) methods has been correlated with the effectiveness, long-term compliance and commitment to weight management. This study explored treatment satisfaction associated with different WL methods among patients with obesity. Cross-sectional data were analysed from the 2012 US National Health and Wellness Survey. Respondents with obesity were categorized as having a WL procedure (e.g., gastric bypass and gastric banding) or using a prescription medication for WL (Sur/Rx), vs. using self-modification WL techniques (e.g., diet, exercise and WL supplements). Overall satisfaction with current WL methods was assessed among the obese and the overweight/obese with type 2 diabetes mellitus (T2DM). Of the 22 927 respondents with obesity, 58.4% took no current action to lose weight, 2.3% were identified as Sur/Rx and 39.3% were identified as self-modification. The Sur/Rx group reported being very/extremely satisfied more frequently than the self-modification group (39.3% vs. 20.2%, P < 0.001). Similarly, respondents with T2DM that were overweight/obese reported higher satisfaction in the Sur/Rx vs. the self modification group (46.6% vs. 22.7%, P < 0.001). Satisfaction with WL methods was greater for the Sur/Rx vs. the self-modification group. Data suggest the importance of including bariatric surgery and pharmacotherapy as an integral part in comprehensive WL management. PMID- 27008070 TI - Editors' note. PMID- 27008071 TI - THE BIOMEDICALIZATION OF BRAZILIAN BODIES: ANTHROPOLOGICAL PERSPECTIVES. PMID- 27008072 TI - The biomedicalisation of illegal abortion: the double life of misoprostol in Brazil. AB - This paper examines the double life of misoprostol in Brazil, where it is illegally used by women as an abortifacient and legally used in obstetric hospital wards. Based on my doctoral and post-doctoral anthropological research on contraception and abortion in Salvador, Bahia, this paper initially traces the "conversion" of misoprostol from a drug to treat ulcers to a self-administered abortifacient in Latin America, and its later conversion to aneclectic global obstetric tool. It then shows how, while reducing maternal mortality, its use as an illegal abortifacient has reinforced the double reproductive citizenship regime existing in countries with restrictive abortion laws and poor post abortion care services, where poor women using it illegally are stigmatised, discriminated against and exposed to potentially severe health risks. PMID- 27008073 TI - The dilemma of a practice: experiences of abortion in a public maternity hospital in the city of Salvador, Bahia. AB - The article discusses abortion and miscarriage from the perspective of women admitted to a public maternity hospital in Salvador (BA), Brazil. Based on qualitative and quantitative research, it draws on participant observation of everyday hospital life. Taking an ethnographic approach, it addresses the hospital experiences of women who had miscarriages or induced abortions, also presenting the views of health professionals. It argues that the way the institution structures care for abortion and miscarriage involves symbolic processes that profoundly affect women's experiences. The discrimination against women who have had abortions/miscarriages is an integral part of the structure, organization and culture of these institutions, and does not derive solely from the individual actions of healthcare personnel. PMID- 27008074 TI - "Holy scan" or "picture of the baby?" Biomedicalization and stratification in the use of obstetric ultrasound in Rio de Janeiro. AB - Based on ethnographic studies conducted at public and private healthcare facilities in Rio de Janeiro, we argue that the dissemination of (bio)medicalization varies in accordance with the social stratum of the expectant mothers, thereby producing thoroughly distinct fetal and pregnant bodies, as well as different gestational processes. Starting from the basic premise that biomedicalization represents a transformation in the process of medicalization, characterized by the growing incorporation of technoscience into biomedicine, the observed universes displayed different stages in this transformation, consonant with the social stratification of the women who underwent the scans. PMID- 27008075 TI - Low-complexity biotechnology and everyday aspects of "care:" neonatal testing and sickle cell diagnosis in Brazil. AB - The article discusses the link between the use of low-complexity biotechnologies and the diverse notions of "care" involved in the process of diagnosing sickle cell disease. It analyses the stories of four different patients and their families, all collected during ethnographic fieldwork, that illustrate several aspects of the experience of living with the condition. These stories demonstrate the presence of what Mol called the "logic of care," showing how the everyday use of diagnostic technology is set within life flows that relate to other realms of experience with biomedicine, kinship groups and community networks. PMID- 27008076 TI - Translating genomics: cancer genetics, public health and the making of the (de)molecularised body in Cuba and Brazil. AB - This article examines how cancer genetics has emerged as a focus for research and healthcare in Cuba and Brazil. Drawing on ethnographic research undertaken in community genetics clinics and cancer genetics services, the article examines how the knowledge and technologies associated with this novel area of healthcare are translated and put to work by researchers, health professionals, patients and their families in these two contexts. It illuminates the comparative similarities and differences in how cancer genetics is emerging in relation to transnational research priorities, the history and contemporary politics of public health and embodied vulnerability to cancer that reconfigures the scope and meaning of genomics as "personalised" medicine. PMID- 27008077 TI - Madness and crime: Zefinha, the longest confined woman in Brazil. AB - Living in a forensic hospital for the last 38 years, Josefa da Silva is the longest female inhabitant surviving the penal and psychiatric regime in Brazil. This paper analyses dossier, judicial proceedings, interviews and photographs about her. The psychiatric report is the key component of the medical and penal doubling of criminal insanity. Twelve psychiatric reports illustrate three time frames of the court files: abnormality, danger, and abandonment. The psychiatric authority over confinement has moved from discipline to security, and from disciplinary security to social assistance. In the arrangement between the penal and psychiatric powers, the judge recognizes the medical authority over the truth of insanity. It is the medicine of the reasons for Zefinha's internment that altered over the decades. PMID- 27008078 TI - Psychiatry, bio-epistemes and the making of adolescence in southern Brazil. AB - Drawing on an ethnographic study in southern Brazil, this paper explores how therapists' attempts to "resist bioreductionist" pharmaceutical use both succeed and crumble. Using a comparative framing, I show that pharmaceuticalization can become an anesthetizing "lid" that interacts with young people's polarizing micro politics and is an outgrowth of multi-generational medico-political family histories. This lid, however, is not air-tight and exceptionalities are born out of these very same histories. I argue that both pharmaceuticalization and exceptions to it emerge not through "resistance" to biopsychiatric logics but from the transformative possibilities that the patterned co-production of social, political, and psychiatric life affords. PMID- 27008079 TI - Cesarean sections, perfecting the technique and standardizing the practice: an analysis of the book Obstetricia, by Jorge de Rezende. AB - This article discusses the development of techniques for cesarean sections by doctors in Brazil, during the 20th century, by analyzing the title "Operacao Cesarea" (Cesarean Section), of three editions of the textbookObstetricia, by Jorge de Rezende. His prominence as an author in obstetrics and his particular style of working, created the groundwork for the normalization of the practice of cesarean sections. The networks of meaning practiced within this scientific community included a "provision for feeling and for action" (Fleck) which established the C-section as a "normal" delivery: showing standards that exclude unpredictability, chaos, and dangers associated with the physiology of childbirth, meeting the demand for control, discipline and safety, qualities associated with practices, techniques and technologies of biomedicine. PMID- 27008080 TI - [Legal remedies: therapeutic markets and the judicialization of the right to health]. AB - This study draw on the struggle of parents of children with mucopolysacchar idosis to access expensive drugs in the name of universal right to health. The work explores how, in Brazil, right-to-health litigation became an alternative pathway to access health care and shows that several public and private stakeholders dispute the judicialization of health. Biotechnology is, therefore, understood to remake human and social worlds as it opens up new spaces of ethical problematization, desire, and political belonging. PMID- 27008081 TI - [Medical borderlands: engineering the body with plastic surgery and hormonal therapies in Brazil]. AB - This paper explores medical borderlands where health and enhancement practices are entangled. It draws on fieldwork carried out in the context of two distinct research projects in Brazil on plastic surgery and sex hormone therapies. These two therapies have significant clinical overlap. Both are made available in private and public healthcare in ways that reveal the class dynamics underlying Brazilian medicine. They also have an important experimental dimension rooted in Brazil's regulatory context and societal expectations placed on medicine as a means for managing women's reproductive and sexual health. Off-label and experimental medical use of these treatments is linked to experimental social use: how women adopt them to respond to the pressures, anxieties and aspirations of work and intimate life. The paper argues that these experimental techniques are becoming morally authorized as routine management of women's health, integrated into mainstream Ob-Gyn healthcare, and subtly blurred with practices of cuidar-se (self-care) seen in Brazil as essential for modern femininity. PMID- 27008082 TI - On the history of medicine in the United States, theory, health insurance, and psychiatry: an interview with Charles Rosenberg. AB - An interview with Charles Rosenberg conducted by Rafael Mantovani in November 2013 that addressed four topics. It first focused on the way in which Rosenberg perceived trends and directions in historical research on medicine in the United States during the second half of the twentieth century. The second focus was on his experience with other important historians who wrote about public health. Thirdly, he discussed his impressions about the current debate on health policy in his country. Finally, the last part explores some themes related to psychiatry and behavior control that have appeared in a number of his articles. PMID- 27008083 TI - [Intersections in the configurations of motherhood in the history of Argentina, 1900-1946: medical and cultural records under the microscope]. PMID- 27008084 TI - [History of family planning: an area of historical health studies to be duly assessed]. PMID- 27008085 TI - [A sociology of lynchings in Brazil]. PMID- 27008086 TI - Characterization of a Polyethylene Glycol-Amphotericin B Conjugate Loaded with Free AMB for Improved Antifungal Efficacy. AB - Amphotericin B (AMB) is a highly hydrophobic antifungal, whose use is limited by its toxicity and poor solubility. To improve its solubility, AMB was reacted with a functionalized polyethylene glycol (PEG), yielding soluble complex AmB-PEG formulations that theoretically comprise of chemically conjugated AMB-PEG and free AMB that is physically associated with the conjugate. Reverse-phase chromatography and size exclusion chromatography methods using HPLC were developed to separate conjugated AMB-PEG and free AmB, enabling the further characterization of these formulations. Using HPLC and dynamic light scattering analyses, it was observed that the AMB-PEG 2 formulation, having a higher molar ratio of 2 AMB: 1 PEG, possesses more free AMB and has relatively larger particle diameters compared to the AMB-PEG 1 formulation, that consists of 1 AMB: 1 PEG. The identity of the conjugate was also verified using mass spectrometry. AMB-PEG 2 demonstrates improved antifungal efficacy relative to AMB-PEG 1, without a concurrent increase in in vitro toxicity to mammalian cells, implying that the additional loading of free AMB in the AMB-PEG formulation can potentially increase its therapeutic index. Compared to unconjugated AMB, AMB-PEG formulations are less toxic to mammalian cells in vitro, even though their MIC50 values are comparatively higher in a variety of fungal strains tested. Our in vitro results suggest that AMB-PEG 2 formulations are two times less toxic than unconjugated AMB with antifungal efficacy on Candida albicans and Cryptococcus neoformans. PMID- 27008087 TI - Radioactivity measurements and risk assessments of spa waters in some areas in Turkey. AB - The current study presents the results of the activity of radionuclides in spa waters, and evaluates their radiological influences on the population consuming these waters in the Central and Eastern Black Sea regions of Turkey. Since these waters are used for therapy and consumption purposes unconsciously, their radiological impact on the people was computed by taking into consideration the annual intake through ingestion of 226Ra, 232Th, 40K, 137Cs and 222Rn. The mean activities were estimated to be 11.35 for gross alpha, 6.23 for gross beta, 2.96 for 226Ra, 0.42 for 232Th, 0.069 for 137Cs, 0.19 for 40K, and 267 Bq L-1 for 222Rn, respectively. The estimated effective doses from spa water were found to be 49.77 uSv a-1 (226Ra), 5.95 uSv a-1 (232Th), 0.07 uSv a-1 (137Cs), 0.83 uSv a 1 (40K) and 56.03 uSv a-1 (222Rn). These values were evaluated and compared with related verified values from literature. Also, physico-chemical characterizations of spa water samples considered in the current study were investigated. This study would be useful for consumers and official authorities for the assessment of radiation exposure risk due to usage of the considered spa waters. PMID- 27008088 TI - Changes in the MicroRNA Profile of the Mandible of Ovariectomized Mice. AB - BACKGROUND/AIMS: In postmenopausal women, a decrease in bone mineral density (BMD) at the hip and spine is associated with an increased risk of tooth loss, possibly caused by the loss of the alveolar bone. The present study explored the effect of the ovariectomy (OVX) of mice on the miRNA expression profile of their bones. METHODS: Micro-CT and histological analysis were performed on mice following OVX or sham-operation using the right mandibles. The left mandibles were used for microarray and quantitative RT-PCR to explore the change in their miRNA expression profile. The differentially expressed miRNAs (DEmiRs) of the OVX and sham-operated mice were analyzed by constructing the miRNA-mRNA-function complex network. We then also analyzed the different roles of the regulation of miRNAs in the mandible and femur by combining public data from GEO. RESULTS: OVX could lead to a significant decrease in the BMD in the mandible. A total of 53 DEmiRs including, 18 up-regulated and 35 down-regulated miRNAs, were identified. The analysis of the miRNA-mRNA-pathway complex network suggested that miR-17-5p and miRNA-297a-5p were potential biomarkers in the development of mandibles of OVX mice. A comparison of the analysis data on the mandible and femur showed that the transforming growth factor-beta signaling pathway was specifically regulated in the mandible, whereas the Wnt signaling pathway was specifically regulated in the femur. Moreover, miR-17-5p and miR-133a-3p showed different expression tendencies in the mandible and in the femur after OVX. CONCLUSION: This study provides an integrated function analysis of miRNA in mandibles after OVX and of miR-17-5p and miR-133a-3p as potential biomarkers. Moreover, the mechanism in mandibles may not be comparable with that in femurs with estrogen deficiency. PMID- 27008089 TI - Evaluation Studies of Robotic Rollators by the User Perspective: A Systematic Review. AB - BACKGROUND: Robotic rollators enhance the basic functions of established devices by technically advanced physical, cognitive, or sensory support to increase autonomy in persons with severe impairment. In the evaluation of such ambient assisted living solutions, both the technical and user perspectives are important to prove usability, effectiveness and safety, and to ensure adequate device application. OBJECTIVE: The aim of this systematic review is to summarize the methodology of studies evaluating robotic rollators with focus on the user perspective and to give recommendations for future evaluation studies. METHODS: A systematic literature search up to December 31, 2014, was conducted based on the Cochrane Review methodology using the electronic databases PubMed and IEEE Xplore. Articles were selected according to the following inclusion criteria: evaluation studies of robotic rollators documenting human-robot interaction, no case reports, published in English language. RESULTS: Twenty-eight studies were identified that met the predefined inclusion criteria. Large heterogeneity in the definitions of the target user group, study populations, study designs and assessment methods was found across the included studies. No generic methodology to evaluate robotic rollators could be identified. We found major methodological shortcomings related to insufficient sample descriptions and sample sizes, and lack of appropriate, standardized and validated assessment methods. Long-term use in habitual environment was also not evaluated. CONCLUSIONS: Apart from the heterogeneity, methodological deficits in most of the identified studies became apparent. Recommendations for future evaluation studies include: clear definition of target user group, adequate selection of subjects, inclusion of other assistive mobility devices for comparison, evaluation of the habitual use of advanced prototypes, adequate assessment strategy with established, standardized and validated methods, and statistical analysis of study results. Assessment strategies may additionally focus on specific functionalities of the robotic rollators allowing an individually tailored assessment of innovative features to document their added value. PMID- 27008090 TI - When Phase Contrast Fails: ChainTracer and NucTracer, Two ImageJ Methods for Semi Automated Single Cell Analysis Using Membrane or DNA Staining. AB - Within bacterial populations, genetically identical cells often behave differently. Single-cell measurement methods are required to observe this heterogeneity. Flow cytometry and fluorescence light microscopy are the primary methods to do this. However, flow cytometry requires reasonably strong fluorescence signals and is impractical when bacteria grow in cell chains. Therefore fluorescence light microscopy is often used to measure population heterogeneity in bacteria. Automatic microscopy image analysis programs typically use phase contrast images to identify cells. However, many bacteria divide by forming a cross-wall that is not detectable by phase contrast. We have developed 'ChainTracer', a method based on the ImageJ plugin ObjectJ. It can automatically identify individual cells stained by fluorescent membrane dyes, and measure fluorescence intensity, chain length, cell length, and cell diameter. As a complementary analysis method we developed 'NucTracer', which uses DAPI stained nucleoids as a proxy for single cells. The latter method is especially useful when dealing with crowded images. The methods were tested with Bacillus subtilis and Lactococcus lactis cells expressing a GFP-reporter. In conclusion, ChainTracer and NucTracer are useful single cell measurement methods when bacterial cells are difficult to distinguish with phase contrast. PMID- 27008091 TI - Performance Enhancement of Silicon Alloy-Based Anodes Using Thermally Treated Poly(amide imide) as a Polymer Binder for High Performance Lithium-Ion Batteries. AB - The development of silicon-based anodes with high capacity and good cycling stability for next-generation lithium-ion batteries is a very challenging task due to the large volume changes in the electrodes during repeated cycling, which results in capacity fading. In this work, we synthesized silicon alloy as an active anode material, which was composed of silicon nanoparticles embedded in Cu Al-Fe matrix phases. Poly(amide imide)s, (PAI)s, with different thermal treatments were used as polymer binders in the silicon alloy-based electrodes. A systematic study demonstrated that the thermal treatment of the silicon alloy electrodes at high temperature made the electrodes mechanically strong and remarkably enhanced the cycling stability compared to electrodes without thermal treatment. The silicon alloy electrode thermally treated at 400 degrees C initially delivered a discharge capacity of 1084 mAh g(-1) with good capacity retention and high Coulombic efficiency. This superior cycling performance was attributed to the strong adhesion of the PAI binder resulting from enhanced secondary interactions, which maintained good electrical contacts between the active materials, electronic conductors, and current collector during cycling. These findings are supported by results from X-ray photoelectron spectroscopy, scanning electron microscopy, and a surface and interfacial cutting analysis system. PMID- 27008092 TI - Does Embryo Culture Medium Influence the Health and Development of Children Born after In Vitro Fertilization? AB - In animal studies, extensive data revealed the influence of culture medium on embryonic development, foetal growth and the behaviour of offspring. However, this impact has never been investigated in humans. For the first time, we investigated in depth the effects of embryo culture media on health, growth and development of infants conceived by In Vitro Fertilization until the age of 5 years old. This single-centre cohort study was based on an earlier randomized study. During six months, in vitro fertilization attempts (No. 371) were randomized according to two media (Single Step Medium--SSM group) or Global medium (Global group). This randomized study was stopped prematurely as significantly lower pregnancy and implantation rates were observed in the SSM group. Singletons (No. 73) conceived in the randomized study were included (42 for Global and 31 for SSM). The medical data for gestational, neonatal and early childhood periods were extracted from medical records and parental interviews (256 variables recorded). The developmental profiles of the children in eight domains (social, self-help, gross motor, fine motor, expressive language, language comprehension, letter knowledge and number knowledge--270 items) were compared in relation to the culture medium. The delivery rate was significantly lower in the SSM group than in the Global group (p<0.05). The culture medium had no significant effect on birthweight, risk of malformation (minor and major), growth and the frequency of medical concerns. However, the children of the Global group were less likely than those of the SSM group to show developmental problems (p = 0.002), irrespective of the different domains. In conclusion, our findings showed that the embryo culture medium may have an impact on further development. PMID- 27008094 TI - Daily lives of residents with dementia in nursing homes: development of the Maastricht electronic daily life observation tool. AB - BACKGROUND: Daily life is a dynamic and multidimensional concept, for which appropriate assessment tools are lacking. This study describes the development of the Maastricht Electronic Daily Life Observation tool (MEDLO-tool), a freely accessible, easy to use, electronic observation tool to assess relevant daily life aspects for nursing home residents with dementia. METHODS: (1) Determining relevant aspects of daily life for nursing home residents with dementia based on a literature search and expert interviews; (2) pilot testing observation procedures and operationalizations of the aspects of daily life; and (3) exploring inter-rater reliability and feasibility of the tool in a nursing home facility with 16 residents (56% female, mean age: 77). RESULTS: The following aspects of daily life are assessed with the MEDLO-tool: (1) activity (activity performed by resident, engagement in this activity, and the degree of physical effort); (2) physical environment (location of the resident and interaction with the physical environment); (3) social interaction (the level and type of social interaction, and with whom this social interaction took place); and (4) emotional well-being (mood and agitation). Each aspect of daily life is observed and scored using standardized scoring options. Agreement on the aspects is high with an average absolute agreement of 86%. Users of the MEDLO-tool indicated that it was feasible in practice and contained clear operationalization of the aspects of daily life. CONCLUSIONS: The MEDLO-tool is a promising tool to gain real time insight into the aspects of the daily lives of nursing home residents with dementia. PMID- 27008093 TI - Why Do You Believe in God? Relationships between Religious Belief, Analytic Thinking, Mentalizing and Moral Concern. AB - Prior work has established that analytic thinking is associated with disbelief in God, whereas religious and spiritual beliefs have been positively linked to social and emotional cognition. However, social and emotional cognition can be subdivided into a number of distinct dimensions, and some work suggests that analytic thinking is in tension with some aspects of social-emotional cognition. This leaves open two questions. First, is belief linked to social and emotional cognition in general, or a specific dimension in particular? Second, does the negative relationship between belief and analytic thinking still hold after relationships with social and emotional cognition are taken into account? We report eight hypothesis-driven studies which examine these questions. These studies are guided by a theoretical model which focuses on the distinct social and emotional processing deficits associated with autism spectrum disorders (mentalizing) and psychopathy (moral concern). To our knowledge no other study has investigated both of these dimensions of social and emotion cognition alongside analytic thinking. We find that religious belief is robustly positively associated with moral concern (4 measures), and that at least part of the negative association between belief and analytic thinking (2 measures) can be explained by a negative correlation between moral concern and analytic thinking. Using nine different measures of mentalizing, we found no evidence of a relationship between mentalizing and religious or spiritual belief. These findings challenge the theoretical view that religious and spiritual beliefs are linked to the perception of agency, and suggest that gender differences in religious belief can be explained by differences in moral concern. These findings are consistent with the opposing domains hypothesis, according to which brain areas associated with moral concern and analytic thinking are in tension. PMID- 27008095 TI - Effects of Cinnamon (C. zeylanicum) Bark Oil Against Taxanes-Induced Damages in Sperm Quality, Testicular and Epididymal Oxidant/Antioxidant Balance, Testicular Apoptosis, and Sperm DNA Integrity. AB - The aim of this study was to investigate whether cinnamon bark oil (CBO) has protective effect on taxanes-induced adverse changes in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular apoptosis, and sperm DNA integrity. For this purpose, 88 adult male rats were equally divided into 8 groups: control, CBO, docetaxel (DTX), paclitaxel (PTX), DTX+PTX, DTX+CBO, PTX+CBO, and DTX+PTX+CBO. CBO was given by gavage daily for 10 weeks at the dose of 100 mg/kg. DTX and PTX were administered by intraperitoneal injection at the doses of 5 and 4 mg/kg/week, respectively, for 10 weeks. DTX+PTX and DTX+PTX+CBO groups were treated with DTX during first 5 weeks and PTX during next 5 weeks. DTX, PTX, and their mixed administrations caused significant decreases in absolute and relative weights of all reproductive organs, testosterone level, sperm motility, concentration, glutathione level, and catalase activity in testicular and epididymal tissues. They also significantly increased abnormal sperm rate, testicular and epididymal malondialdehyde level, apoptotic germ cell number, and sperm DNA fragmentation and significantly damaged the histological structure of testes. CBO consumption by DTX-, PTX-, and DTX+PTX-treated rats provided significant ameliorations in decreased relative weights of reproductive organs, decreased testosterone, decreased sperm quality, imbalanced oxidant/antioxidant system, increased apoptotic germ cell number, rate of sperm with fragmented DNA, and severity of testicular histopathological lesions induced by taxanes. In conclusion, taxanes cause impairments in sperm quality, testicular and epididymal oxidant/antioxidant balance, testicular histopathological structure, and sperm DNA integrity, and long-term CBO consumption protects male reproductive system of rats. PMID- 27008096 TI - Depressive Symptoms and Suicidal Ideation in College Students: The Mediating and Moderating Roles of Hopelessness, Alcohol Problems, and Social Support. AB - OBJECTIVE: Mixed evidence for the associations among depression, hopelessness, alcohol problems, and suicidal ideation in college students may be due to the influence of social support. METHOD: A moderated-mediation analysis was conducted to examine relationships among suicide risk factors in 2,034 college students. RESULTS: Social support moderated the relation between depressive symptoms and hopelessness in predicting suicidal thoughts; specifically, the association between depressive symptoms and hopelessness was diminished among those students with high levels of social support. This resulted in attenuated indirect associations between depressive symptoms and suicidal ideation via hopelessness. Alcohol problems were associated with likelihood of experiencing suicidal ideation, but not severity. CONCLUSION: Social support may be a key variable for suicide prevention among college students. PMID- 27008097 TI - Low socio-economic status associated with unhealthy weight in six-year-old Swedish children despite higher levels of physical activity. AB - AIM: Socio-economic status is an important determinant of physical activity, sedentary behaviour and body mass index, but these associations are contradictory in younger children. We investigated the associations between parental socio economic status, physical activity, sedentary behaviour and body mass index in six-year-old children, to identify possible differences in physical activity between socio-economic groups. METHODS: The study comprised 621 children from Stockholm suburbs, recruited from, A healthy school start, a cluster-randomised controlled intervention study. A cross-sectional study was performed using baseline data. Physical activity and sedentary behaviour were assessed by accelerometry, body weight and height were measured, and body mass index was calculated. Sedentary behaviour was also assessed using a questionnaire. RESULTS: We found that 12% of the study population were overweight and 9% were obese. Children from families with low socio-economic status were more physically active and slightly less sedentary, but were almost twice as likely to be overweight or obese than children from high socio-economic status, irrespective of the child's sex. CONCLUSION: Low socio-economic status was associated with higher physical activity, lower sedentary behaviour and an unhealthier weight status compared to high socio-economic status, suggesting a role of diet as a cause of the higher overweight and obesity prevalence. PMID- 27008098 TI - NESARC Findings on Increased Prevalence of Marijuana Use Disorders-Consistent With Other Sources of Information. PMID- 27008099 TI - Immunosuppressive Treatment Can Alter Visual Performance in the Royal College of Surgeons Rat. AB - PURPOSE: Immunosuppression is frequently employed to enhance survival of xenografted human cells as part of translational proof-of-concept studies. However, the potential effects of this treatment are easily overlooked. METHODS: As part of baseline testing in the dark-eyed variant of the dystrophic Royal College of Surgeons (RCS) rat, we documented the time course of retinal degenerative changes versus Long Evans controls using bright field retinal imaging, fluorescein angiography, and histology and examined the impact of immunosuppression on visual function. Rats received either no treatment or systemic immunosuppression with oral cyclosporine A and injectable dexamethasone and subsequently underwent functional evaluation by optomotor response testing and electroretinography (ERG) at multiple intervals from P45 to P180. RESULTS: Immunosuppressed RCS animals demonstrated poorer performance on functional tests than age-matched untreated rats during the earlier stages of degeneration, including significantly lower spatial acuities on optomotor threshold testing and significantly lower b-wave amplitudes on scotopic and photopic ERGs. Retinal imaging documented the progression of degenerative changes in the RCS fundus and histologic evaluation of the RCS retina confirmed progressive thinning of the outer nuclear layer. CONCLUSIONS: A standard regimen of cyclosporine A plus dexamethasone, administered to RCS rats, results in demonstrable systemic side effects and depressed scores on behavioral and electrophysiological testing at time points before P90. The source of the functional impairment was not identified. This finding has implications for the interpretation of data generated using this commonly used translational model. PMID- 27008100 TI - Gene expression pattern of glucose transporters in the skeletal muscles of newly hatched chicks. AB - The gene expression pattern of the glucose transporters (GLUT1, GLUT3, GLUT8, and GLUT12) among pectoralis major and minor, biceps femoris, and sartorius muscles from newly hatched chicks was examined. GLUT1 mRNA level was higher in pectoralis major muscle than in the other muscles. Phosphorylated AKT level was also high in the same muscle, suggesting a relationship between AKT and GLUT1 expression. PMID- 27008101 TI - The role of stem cells in limb regeneration. AB - Limb regeneration is a complex yet fascinating process observed to some extent in many animal species, though seen in its entirety in urodele amphibians. Accomplished by formation of a morphologically uniform intermediate, the blastema, scientists have long attempted to define the cellular constituents that enable regrowth of a functional appendage. Today, we know that the blastema consists of a variety of multipotent progenitor cells originating from a variety of tissues, and which contribute to limb tissue regeneration in a lineage restricted manner. By continuing to dissect the role of stem cells in limb regeneration, we can hope to one day modulate the human response to limb amputation and facilitate regrowth of a working replacement. PMID- 27008103 TI - Influence of cochlear implantation on vestibular function. AB - Conclusion Vestibular function in patients can be damaged following cochlear implantation. Therefore, assessing the pre-operative vestibular status, carefully choosing the side of implantation, and preserving function by using minimally invasive surgical techniques are important. Objectives The aim of this study was to assess the influence of cochlear implantation on vestibular function in patients with severe and profound sensorineural hearing loss, and to analyze a possible correlation between the changes in vestibular testing and post-operative vestibular symptoms. Methods Thirty-four patients were evaluated for vestibular function using the cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP, respectively), and 29 patients underwent caloric tests pre operatively and 4 weeks post-operatively. Results Before surgery, the cVEMPs were recorded bilaterally in 22 patients, unilaterally in eight patients, and absent bilaterally in four patients. The oVEMPs were recorded bilaterally in 19 patients, unilaterally in six patients, and absent bilaterally in nine patients. After implantation, the cVEMPs were absent in 10 patients and the oVEMPs were absent in seven patients on the implanted side. Caloric tests demonstrated canal paresis in 17 patients, and normal responses were recorded in 12 of the 29 patients pre-operatively. There was a significant decrease post-implantation in the ear implanted, with the exception of two patients. Two patients presented with vertigo and another two patients reported slight unsteadiness post operatively, but all symptoms resolved within 7 days. The impaired vestibular function did not correlate with vestibular symptoms, age, or gender. Function on the contralateral side remained unaffected. PMID- 27008102 TI - Incident Tick-Borne Infections in a Cohort of North Carolina Outdoor Workers. AB - Tick-borne diseases cause substantial morbidity throughout the United States, and North Carolina has a high incidence of spotted fever rickettsioses and ehrlichiosis, with sporadic cases of Lyme disease. The occupational risk of tick borne infections among outdoor workers is high, particularly those working on publicly managed lands. This study identified incident tick-borne infections and examined seroconversion risk factors among a cohort of North Carolina outdoor workers. Workers from the North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife (n = 159) were followed for 2 years in a randomized controlled trial evaluating the effectiveness of long-lasting permethrin impregnated clothing. Antibody titers against Rickettsia parkeri, Rickettsia rickettsii, "Rickettsia amblyommii," and Ehrlichia chaffeensis were measured at baseline (n = 130), after 1 year (n = 82), and after 2 years (n = 73). Titers against Borrelia burgdorferi were measured at baseline and after 2 years (n = 90). Baseline seroprevalence, defined as indirect immunofluorescence antibody titers of 1/128 or greater, was R. parkeri (24%), R. rickettsii (19%), "R. amblyommii" (12%), and E. chaffeensis (4%). Incident infection was defined as a fourfold increase in titer over a 1-year period. There were 40 total seroconversions to at least one pathogen, including R. parkeri (n = 19), "R. amblyommii" (n = 14), R. rickettsii (n = 9), and E. chaffeensis (n = 8). There were no subjects whose sera were reactive to B. burgdorferi C6 antigen. Thirty eight of the 40 incident infections were subclinical. The overall risk of infection by any pathogen during the study period was 0.26, and the risk among the NC Division of Forest Resources workers was 1.73 times that of workers in other divisions (95% confidence interval [CI]: 1.02, 2.92). The risk of infection was lower in subjects wearing permethrin-impregnated clothing, but not significantly (risk ratio = 0.81; 95% CI: 0.47, 1.39). In summary, outdoor workers in North Carolina are at high risk of incident tick-borne infections, most of which appear to be asymptomatic. PMID- 27008104 TI - Does radiography advanced practice improve patient outcomes and health service quality? A systematic review. AB - OBJECTIVE: To investigate the impact of radiographer advanced practice on patient outcomes and health service quality. METHODS: Using the World Health Organization definition of quality, this review followed the Centre for Reviews and Dissemination guidance for undertaking reviews in healthcare. A range of databases were searched using a defined search strategy. Included studies were assessed for quality using a tool specifically developed for reviewing studies of diverse designs, and data were systematically extracted using electronic data extraction pro forma. RESULTS: 407 articles were identified and reviewed against the inclusion/exclusion criteria. Nine studies were included in the final review, the majority (n = 7) focusing on advanced radiography practice within the UK. Advanced practice activities considered were radiographer reporting, leading patient review clinics and barium enema examinations. The articles were generally considered to be of low-to-moderate quality, with most evaluating advanced practice within a single centre. With respect to specific quality dimensions, the included studies considered cost reduction, patient morbidity, time to treatment and patient satisfaction. No articles reported data relating to time to diagnosis, time to recovery or patient mortality. CONCLUSION: Radiographer advanced practice is an established activity both in the UK and internationally. However, evidence of the impact of advanced practice in terms of patient outcomes and service quality is limited. ADVANCES IN KNOWLEDGE: This systematic review is the first to examine the evidence base surrounding advanced radiography practice and its impact on patient outcomes and health service quality. PMID- 27008105 TI - The value of thyroid shielding in intraoral radiography. AB - OBJECTIVES: To evaluate the utility of the application of a thyroid shield in intraoral radiography when using rectangular collimation. METHODS: Experimental data were obtained by measuring the absorbed dose at the position of the thyroid gland in a RANDO((r)) (The Phantom Laboratory, Salem, NY) male phantom with a dosemeter. Four protocols were tested: round collimation and rectangular collimation, both with and without thyroid shield. Five exposure positions were deployed: upper incisor (Isup), upper canine (Csup), upper premolar (Psup), upper molar (Msup) and posterior bitewing (BW). Exposures were made with 70 kV and 7 mA and were repeated 10 times. The exposure times were as recommended for the exposure positions for the respective collimator type by the manufacturer for digital imaging. The data were statistically analyzed with a three-way ANOVA test. Significance was set at p < 0.01. RESULTS: The ANOVA test revealed that the differences between mean doses of all protocols and geometries were statistically significant, p < 0.001. For the Isup, thyroid dose levels were comparable with both collimators at a level indicating primary beam exposure. Thyroid shield reduced this dose with circa 75%. For the Csup position, round collimation also revealed primary beam exposure, and thyroid shield yield was 70%. In Csup with rectangular collimation, the thyroid dose was reduced with a factor 4 compared with round collimation and thyroid shield yielded an additional 42% dose reduction. The thyroid dose levels for the Csup, Psup, Msup and BW exposures were lower with rectangular collimation without thyroid shield than with round collimation with thyroid shield. With rectangular collimation, the thyroid shield in Psup, Msup and BW reduced the dose 10% or less, where dose levels were already low, implying no clinical significance. CONCLUSIONS: For the exposures in the upper anterior region, thyroid shield results in an important dose reduction for the thyroid. For the other exposures, thyroid shield augments little to the reduction achieved by rectangular collimation. The use of thyroid shield is to be advised, when performing upper anterior radiography. PMID- 27008106 TI - Evaluation of the effects of positioning and configuration on contrast-to-noise ratio in the quality control of a 3D Accuitomo 170 dental CBCT system. AB - OBJECTIVES: This study evaluated the effect of phantom positioning and the configuration of phantom inserts on the measurement of contrast-to-noise ratio (CNR) in dental CBCT. The work aimed to make pragmatic suggestions for the remedial tolerances for CNR measurements in the routine quality control (QC) of a three-dimensional Accuitomo 170 dental CBCT system (J Morita, Kyoto, Japan). METHODS: Images of the SEDENTEXCT (safety and efficacy of a new and emerging dental X-ray modality) IQ (image quality) dental CBCT phantom (Leeds Test Objects Ltd, Boroughbridge, UK) were acquired and measurements of CNR were obtained in three configurations of inserts and in six phantom orientations for one of the configurations. Five consecutive images were acquired in each case, to assess the reproducibility of measurements. RESULTS: Reproducibility of measurements ranged from 1.8% to 4.6%. For the CNR measurements in the three phantom configurations, the ratio of the measured CNR to the minimum value was 2.1 +/- 0.2 times the minimum value for Delrin((r)) (DuPont UK Ltd, Stevenage, UK). For aluminium, there was no significant variation between configurations and for the other three materials, the ratio ranged from 20% to 50%. Significant variations in CNR with phantom position were observed, with differences between the maximum and minimum values ranging from 10% to 60%. Absolute differences in CNR from the minimum value ranged from <0.1 to 2.1 with phantom configuration and from 1.2 to 4.5 with phantom position. CONCLUSIONS: The effects of phantom configuration and positioning on CNR measurements for dental CBCT QC were investigated and possible remedial tolerances suggested. PMID- 27008107 TI - Social Support Indirectly Predicts Problem Drinking Through Reduced Psychological Distress. AB - BACKGROUND: The experience of psychological distress can contribute to problem drinking in young adults. Social support can protect against the development of distress and thus may indirectly minimize problem drinking. OBJECTIVE: To test a model of problem drinking in young adults based on the concepts of social support and psychological distress. METHODS: A two-wave panel study was conducted over the course of one year, during 2014-15, with 211 university students (M age = 21.06 years, SD = 1.60 years) who completed online survey measures of problem drinking, various indicators of social support, and various indicators of psychological distress. RESULTS: The data were analyzed with structural equation modeling. After controlling for concurrent problem drinking and psychological distress, there was no direct prospective effect of social support on problem drinking. However, social support predicted reductions in psychological distress over time, and this reduced psychological distress predicted reductions in problem drinking over time. Therefore, social support exhibited a significant indirect effect on problem drinking. CONCLUSION: Social support from friends, emotional support, and informational support combine to form a protective factor that mitigates the risk of problem drinking in young adults through reduced psychological distress. PMID- 27008108 TI - Patients need a strong voice in how NHS is run. AB - Politicians, professionals and the public would surely all agree that patients must have a say in the way they access and receive NHS care, and the opportunity to provide feedback easily on their experience. However, the reality is that patients and other service users often struggle to be heard, not least if they seek redress when the quality of care does not meet their expectations. PMID- 27008110 TI - Cumbrian heart centre set to benefit from sale of donated dairy cow. AB - A former cardiology nurse turned farmer has donated a cow to a Carlisle hospital. PMID- 27008109 TI - Nurse associate role should not be used to replace nurses, unions say. AB - The proposed nursing associate role could lead to a further fall in the numbers of registered nurses, say nursing unions. PMID- 27008111 TI - Breaking down barriers for BME staff 'is everyone's responsibility'. AB - Everyone in the NHS needs to take responsibility for championing black and minority ethnic (BME) staff, a nurse leader on diversity issues has said. PMID- 27008112 TI - American hospital puts patients in the driving seat. AB - A US hospital that adopted a way of working used by car manufacturers has seen nurses' work time reduce and patient satisfaction soar. PMID- 27008113 TI - Leadership style has influence on staff retention. AB - A study highlighting the importance of leadership in hospitals for retaining and motivating nursing staff could have a wider global impact, according to the RCN head of policy. PMID- 27008114 TI - Ebola nurses given standing ovation after talking about their experiences. AB - Two nurses who fought to prevent the spread of the Ebola virus have been praised for their efforts. PMID- 27008117 TI - Patients Association film shows pressures on healthcare staff. AB - A film highlighting the consequences of the enormous pressures faced by nurses and other healthcare workers forms part of a campaign to review NHS and social care funding. PMID- 27008115 TI - RCN Wales reveals its first nursing education strategy. AB - RCN Wales has published its first nursing education strategy to equip nurses with the skills and competencies required to work with increasingly complex patients in a variety of settings. PMID- 27008118 TI - Plans for mental health discharge. AB - People being discharged from inpatient mental health settings should be given a recovery plan that provides information on support networks and crisis management, according to the National Institute for Health and Care Excellence. PMID- 27008119 TI - QNI survey reveals jump in district nurse training numbers won't last. AB - Fresh concerns have been raised over the future of district nursing, as new figures reveal the number qualifying from specialist postgraduate programmes is set to fall despite rising demand for services. PMID- 27008120 TI - Taking palliative care to patients. AB - A rapid response service for patients at the end of life has experienced higher than expected demand in its first months. PMID- 27008121 TI - The NHS needs you - and it has to work harder than ever to keep you. AB - The number of employers in the NHS paying extra to attract or retain staff in England is falling. PMID- 27008127 TI - Motor neurone disease. AB - Essential facts Motor neurone disease describes a group of related diseases, affecting the neurones in the brain and spinal cord. Progressive, incurable and life-limiting, MND is rare, with about 1,100 people developing it each year in the UK and up to 5,000 people affected at any one time. One third of people will die within a year of diagnosis and more than half within two years. About 5% to 10% are alive at ten years. PMID- 27008128 TI - Final lessons from road-testing revalidation. AB - As of April 1, all nurses and midwives will have to revalidate with the Nursing and Midwifery Council every three years to remain on the register. The largest of the UK revalidation pilots took place at Aneurin Bevan University Health Board in Wales. This article looks at how the pilot experience has equipped the board to predict nurses concerns and steer them through the revalidation process. PMID- 27008129 TI - A good way to die. AB - An end of life care service is providing joined-up care for patients. Care co ordinators arrange packages of care so patients can die in the place of their choice - often at home. The result is high satisfaction rates among patients, families and staff. PMID- 27008142 TI - Removing rancour in examining mistakes would be new for the NHS. AB - The health secretary's announcements relating to greater transparency in the health service (news, March 16) are a welcome development, particularly with regard to reducing mistakes by fully acknowledging and learning from any at an early stage; and modernising the fitness to practise procedures. PMID- 27008143 TI - Let's hope new transparency puts paid to quick-fix blame culture. AB - It was great to read your coverage of health secretary Jeremy Hunt's latest announcement to improve transparency in the health service (news, March 16). PMID- 27008144 TI - Accentuate the positives to attract nurses of the future. AB - Stereotypes and cultural cringe may still be keeping men out of nursing, but the way to solve the recruitment and retention challenges is not gender-focused (analysis, March 9). PMID- 27008145 TI - We need to promote nursing as a profession to which men will aspire. AB - Your article on how stereotypes about nurses are keeping men out of the profession really grabbed my attention (analysis, March 9). PMID- 27008147 TI - One legacy of Lord Briggs is the value placed on nurse research. AB - The announcement of the death of Asa Briggs - Lord Briggs of Lewes - on March 15 brings to mind the debt the nursing profession owes his wise stewardship of a committee that examined aspects of the profession. PMID- 27008149 TI - The profession needs to come together like never before. AB - As I prepare to leave the RCN to join the International Council of Nurses, I am struck by what a huge moment this is for the profession. PMID- 27008151 TI - How to perform a tracheostomy dressing and inner cannula change. AB - RATIONALE AND KEY POINTS: Proactive tracheostomy management increases patient safety and reduces adverse events. ? A cleaning regimen performed every four hours reduces the risk of a blocked tracheostomy cannula, complete tube occlusion and respiratory arrest. ? Sterile tracheostomy dressings allow secretions from the stoma to be absorbed and prevent pressure damage from the tracheostomy tube. ? Regular dressing changes and skin inspection permit timely identification of inflammatory processes and skin excoriation, enabling prompt treatment to be instigated. REFLECTIVE ACTIVITY: Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How this article will change your practice. 2. How you intend to develop your knowledge and skills regarding tracheostomy management. PMID- 27008152 TI - Supported decision making: the rights of people with dementia. AB - The Mental Capacity Act 2005 is used to assess a person's decision-making ability and to make a best interests decision where the individual lacks the capacity to do so. The act was considered to have the potential to maximise the autonomy of individuals with mental or cognitive impairments, but this has not been fully realised. Since the act came into force, the United Nations Convention on the Rights of Persons with Disabilities has challenged many of the principles underpinning the act. That challenge and how existing provisions in the act can be implemented to increase autonomy and control for people with cognitive or mental impairments are discussed. The principles of the convention are described and potential future amendments to the law are identified. PMID- 27008153 TI - Exploring assistant practitioners' views of their role and training. AB - AIM: To examine the views of assistant practitioners and trainee assistant practitioners regarding experiences of practice in relation to the autonomy of the role and level of supervision, the training involved and support experienced in undertaking the foundation degree, and the effects of the assistant practitioner role in the workplace. METHOD: A service evaluation was undertaken in which a small cross-sectional quantitative survey was distributed to trainee assistant practitioners undertaking the foundation degree, and assistant practitioners who had previously completed the foundation degree or who had qualified via another route. RESULTS: A total of 93 questionnaires were returned. The data indicate that there is some uncertainty surrounding the skills and competence of those undertaking the foundation degree, and a lack of opportunity for career progression for unregistered staff. CONCLUSION: Increased understanding of the scope and role of assistant practitioners and the academic requirements of the foundation degree is required to increase assistant practitioner numbers. PMID- 27008154 TI - Medicines optimisation: priorities and challenges. AB - Medicines optimisation is promoted in a guideline published in 2015 by the National Institute for Health and Care Excellence. Four guiding principles underpin medicines optimisation: aim to understand the patient's experience; ensure evidence-based choice of medicines; ensure medicines use is as safe as possible; and make medicines optimisation part of routine practice. Understanding the patient experience is important to improve adherence to medication regimens. This involves communication, shared decision making and respect for patient preferences. Evidence-based choice of medicines is important for clinical and cost effectiveness. Systems and processes for the reporting of medicines-related safety incidents have to be improved if medicines use is to be as safe as possible. Ensuring safe practice in medicines use when patients are transferred between organisations, and managing the complexities of polypharmacy are imperative. A medicines use review can help to ensure that medicines optimisation forms part of routine practice. PMID- 27008155 TI - Agitation. AB - As a staff nurse on a surgical step-down unit, I care for patients with surgical needs who require monitoring. PMID- 27008156 TI - Lessons from rejection. AB - Finding out you did not get that coveted job can dent your confidence, but it is important to pick yourself up and learn from the experience, say recruiters. PMID- 27008158 TI - Bank nursing: a flexible option. AB - For anyone who would like more say about when they work, or to earn some extra money, working as a bank nurse could be the solution. Employers are constantly on the lookout for registered nurses who can join the bank and fill in shifts in a wide range of settings. PMID- 27008159 TI - Student life - Handling work pressure. AB - An ageing population coupled with the increase in treatable illnesses has led to 'health promotion' and 'self-management' becoming buzz words in today's NHS. PMID- 27008160 TI - Mediterranean Diet and Health-Related Quality of Life in Two Cohorts of Community Dwelling Older Adults. AB - INTRODUCTION: In older adults, the Mediterranean diet is associated with lower risk of chronic diseases, but its association with health-related quality of life (HRQL) is still uncertain. This study assessed the association between the Mediterranean diet and HRQL in 2 prospective cohorts of individuals aged >=60 years in Spain. METHODS: The UAM-cohort (n = 2376) was selected in 2000/2001 and followed-up through 2003. At baseline, diet was collected with a food frequency questionnaire, which was used to develop an 8-item index of Mediterranean diet (UAM-MDP). The Seniors-ENRICA cohort (n = 1911) was recruited in 2008/2010 and followed-up through 2012. At baseline, a diet history was used to obtain food consumption. Mediterranean diet adherence was measured with the PREDIMED score and the Trichopoulou's Mediterranean Diet Score (MSD). HRQL was assessed, at baseline and at the end of follow-up, with the physical and mental component summaries (PCS and MCS) of the SF-36 questionnaire in the UAM-cohort, and the SF 12v.2 questionnaire in the Seniors-ENRICA cohort. Analyses were conducted with linear regression, and adjusted for the main confounders including baseline HRQL. RESULTS: In the UAM-cohort, no significant associations between the UAM-MDP and the PCS or the MCS were found. In the Seniors-ENRICA cohort, a higher PREDIMED score was associated with a slightly better PCS; when compared with the lowest tertile of PREDIMED score, the beta coefficient (95% confidence interval) for PCS was 0.55 (-0.48 to 1.59) in the second tertile, and 1.34 (0.21 to 2.47) in the highest tertile. However, the PREDIMED score was non-significantly associated with a better MCS score. The MSD did not show an association with either the PCS or the MCS. CONCLUSIONS: No clinically relevant association was found between the Mediterranean diet and HRQL in older adults in Spain. PMID- 27008161 TI - Diagnosing Depression in Chronic Pain Patients: DSM-IV Major Depressive Disorder vs. Beck Depression Inventory (BDI). AB - BACKGROUND: Diagnosing depression in chronic pain is challenging due to overlapping somatic symptoms. In questionnaires, such as the Beck Depression Inventory (BDI), responses may be influenced more by pain than by the severity of depression. In addition, previous studies have suggested that symptoms of negative self-image, a key element in depression, are uncommon in chronic pain related depression. The object of this study is to assess the relationship of the somatic and cognitive-emotional items of BDI with the diagnosis of depression, pain intensity, and disability. METHODS: One hundred consecutive chronic pain patients completed the Structured Clinical Interview for DSM Disorders (SCID) for the diagnosis of major depressive disorder (MDD) according to DSM-IV. Two subscales of BDI (negative view of self and somatic-physical function) were created according to the factor model presented by Morley. RESULTS: In the regression analysis, the somatic-physical function factor associated with MDD, while the negative view of self factor did not. Patients with MDD had higher scores in several of the BDI items when analysed separately. Insomnia and weight loss were not dependent on the depression diagnosis. LIMITATIONS: The relatively small sample size and the selected patient sample limit the generalisability of the results. CONCLUSIONS: Somatic symptoms of depression are also common in chronic pain and should not be excluded when diagnosing depression in pain patients. Regardless of the assessment method, diagnosing depression in chronic pain remains a challenge and requires careful interpretation of symptoms. PMID- 27008162 TI - Multiscale Surface-Attached Hydrogel Thin Films with Tailored Architecture. AB - A facile route for the fabrication of surface-attached hydrogel thin films with well-controlled chemistry and tailored architecture on wide range of thickness from nanometers to micrometers is reported. The synthesis, which consists in cross-linking and grafting the preformed and ene-reactive polymer chains through thiol-ene click chemistry, has the main advantage of being well-controlled without the addition of initiators. As thiol-ene click reaction can be selectively activated by UV-irradiation (in addition to thermal heating), micropatterned hydrogel films are easily synthesized. The versatility of our approach is illustrated by the possibility to fabricate various chemical polymer networks, like stimuli-responsive hydrogels, on various solid substrates, such as silicon wafers, glass, and gold surfaces. Another attractive feature is the development of new complex hydrogel films with targeted architecture. The fabrication of various architectures for polymer films is demonstrated: multilayer hydrogel films in which single-networks are stacked one onto the other, interpenetrating networks films with mixture of two networks in the same layer, and nanocomposite hydrogel films where nanoparticles are stably trapped inside the mesh of the network. Thanks to its simplicity and its versatility this novel approach to surface-attached hydrogel films should have a strong impact in the area of polymer coatings. PMID- 27008163 TI - Binary-copolymer system base on low-density lipoprotein-coupled N-succinyl chitosan lipoic acid micelles for co-delivery MDR1 siRNA and paclitaxel, enhances antitumor effects via reducing drug. AB - The development of effective and stable carriers of small interfering RNA (siRNA) is important for treating cancer with multidrug resistance (MDR). We developed a new gene and drug co-delivery system and checked its characteristics. Low-density lipoprotein (LDL) was coupled with N-succinyl chitosan (NSC) Lipoic acid (LA) micelles and co-delivered MDR1 siRNA and paclitaxel (PTX-siRNA/LDL-NSC-LA) to enhance antitumor effects by silencing the MDR gene of tumors (Li et al., Adv Mater 2014;26:8217-8224). In our study, we developed a new type of containing paclitaxel-loaded micelles and siRNA-loaded LDL nanoparticle. This "binary polymer" is pH and reduction dual-sensitive core-crosslinked micelles. PTX siRNA/LDL-NSC-LA had an average particle size of (171.6 +/- 6.42) nm, entrapment efficiency of (93.92 +/- 1.06) %, and drug-loading amount of (12.35% +/- 0.87) %. In vitro, MCF-7 cells, high expressed LDL receptor, were more sensitive to this delivery system than to taxol(r) and cell activity was inhibited significantly. Fluorescence microscopy showed that PTX-siRNA/LDL-NSC-LA was uptaken very conveniently and played a key role in antitumor activity. PTX-siRNA/LDL-NSC-LA protected the siRNA from degradation by macrophage phagocytosis and evidently down-regulated the level of mdr1 mRNA as well as the expression of P-gp. We tested the target ability of PTX-siRNA/LDL-NSC-LA in vivo in tumor-bearing nude mice. Results showed that this system could directly deliver siRNA and PTX to cancer cells. Thus, new co-delivering siRNA and antitumor drugs should be explored for solving MDR in cancer. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1114-1125, 2017. PMID- 27008164 TI - Earth Mover's Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations. AB - Changes in the frequencies of cell subsets that (co)express characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem cell reconstitution, etc. However, although the currently available computational "gating" tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover's Distance (EMD) metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1) reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2) shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3) ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains. PMID- 27008165 TI - The Effects of Chronic Lifelong Activation of the AHR Pathway by Industrial Chemical Pollutants on Female Human Reproduction. AB - Environmental chemicals, such as heavy metals, affect female reproductive function. A biological sensor of the signals of many toxic chemical compounds seems to be the aryl hydrocarbon receptor (AHR). Previous studies demonstrated the environmental of heavy metals in Taranto city (Italy), an area that has been influenced by anthropogenic factors such as industrial activities and waste treatments since 1986. However, the impact of these elements on female fertility in this geographic area has never been analyzed. Thus, in the present study, we evaluated the AHR pathway, sex steroid receptor pattern and apoptotic process in granulosa cells (GCs) retrieved from 30 women, born and living in Taranto, and 30 women who are living in non-contaminated areas (control group), who were undergoing in vitro fertilization (IVF) protocol. In follicular fluids (FFs) of both groups the toxic and essential heavy metals, such as chromiun (Cr), Manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), cadmium (Cd) and lead (Pb), were also analyzed. Higher levels of Cr, Fe, Zn and Pb were found in the FFs of the women from Taranto as compared to the control group, as were the levels of AHR and AHR-dependent cytochrome P450 1A1 and 1B1; while CYP19A1 expression was decreased. The anti-apoptotic process found in the GCs of women fromTaranto was associated with the highest levels of progesterone receptor membrane component 1 (PGRMC1), a novel progesterone receptor, the expression of which is subjected to AHR activated by its highest affinity ligands (e.g., dioxins) or indirectly by other environmental pollutants, such as heavy metals. In conclusion, decreased production of estradiol and decreased number of retrieved mature oocytes found in women from Taranto could be due to chronic exposure to heavy metals, in particular to Cr and Pb. PMID- 27008166 TI - Complications of pancreato-duodenectomy. AB - Pancreato-duodenectomy (PD) is the procedure of choice for management of resectable periampullary and pancreatic cancers and some patients with chronic pancreatitis. PD is one of the most major GI/ HPB surgical procedures performed involving resection of multiple organs and reconstruction with multiple anastomoses. While mortality of PD has been brought down to less than 5% morbidity still remains high.Patients undergoing PD are usually elderly with comorbidities - general complications of a major operation e.g. wound, chest, cardiac and venous thrombo-embolism, are common.The major intra-operative morbidity of PD is bleeding which can be from multiple sites viz. gall bladder bed, choledochal veins, gastro-colic trunk, pancreato-duodenal veins, jejunal veins, uncinate veins and cut surface of pancreas. An aberrant right hepatic artery (from the superior mesenteric artery) can be injured while dissecting the common bile duct.Pancreatic leak is defined as presence of amylase rich (>3x serum amylase) fluid in drain beyond 3 days. It is graded as A (no clinical impact), B (persists, infected) or C (systemic sepsis, reoperation). Investigation of choice is computed tomography; a localized collection can be drained percutaneously. Major leak requires reexploration at which lavage and drainage should be performed; no attempt should be made to repair or redo the anastomosis. Soft pancreas and undilated duct are the two most important risk factors for pancreatic anastomotic leak; role of octreotide to prevent the leak is debatable. Preoperative biliary drainage in the form of endoscopic stenting may reduce bleeding complications by controlling coagulopathy but increases the risk of infective complications.Postoperative bleed can be early or delayed and intra-luminal or intra-abdominal. Early intra-abdominal bleed is surgical - either a slipped ligature e.g. of the gastro-duodenal artery or one of the veins or from the pancreato-duodenal bed; reexploration should be done to control it if it is severe. Early intra-luminal bleed is from one of the anastomoses - commonest being the pancreatic. UGIE rules out bleed from the gastro/duodenal anastomosis (which if present, can be controlled endoscopically). Control of pancreatic stump bleed requires reoperation - taking down anterior layer of the anastomosis or a jejunotomy. Delayed intra-abdominal bleed is from a pseudo aneurysm of an artery, usually gastro-duodenal caused by erosion by an abscess secondary to a leak; treatment of choice is angio-embolization. Delayed intra luminal bleed is because of stress ulcers caused by systemic sepsis usually secondary to a leak and intra-abdominal sepsis.Other common complications include delayed gastric emptying and acute pancreatitis.Reoperations after PD are frequent - commonest cause is bleed, followed by leak; mortality of reexploration is high. Long term complications include anastomotic (PJ/ HJ) stricture, endocrine and exocrine insufficiency and inability to regain weight and poor quality of life. KEY WORDS: pancreato-duodenectomy complications. PMID- 27008167 TI - [Surgical versus non-surgical treatment for 3- and 4-part proximal humerus fractures]. AB - INTRODUCTION: Proximal humerus fractures account for about 45% of all fractures. Treatment of 3- and 4-part fractures is difficult, and the optimal treatment option remains controversial. The aim of the study was to compare surgical and non-surgical treatments of 3- and 4-part fractures of the proximal humerus in adults. METHOD: A prospective study of surgical and non-surgical treatments of 3- and 4-part fractures of the proximal humerus was conducted at the 2nd Department of Orthopedics and Traumatology, University Hospital Bratislava, from September 2010 until September 2013. Patients included in the study were compliant adults patients with 3- and 4-part proximal humerus fractures Neer type IV, V and VI. Twenty patients were treated surgically. The group included 13 women (65%) and 7 men (35%). Mean age was 60.9+/-7.67 (52-80) years. Angle-stable plates (Philos, Synthes) and intramedullary nails (Multilock, Synthes) were used.The non-surgical group included 19 patients, consisting of 12 (63.2%) women and 7 (36.8%) men. Mean age of both sexes was 66.3+/-9.5 (5288) years. Gilchrist bandage was applied for the maximum of 3 weeks. All patients were evaluated at 12 months from treatment using the Constant-Murley scoring system and the Oxford Shoulder Score. Treatment complications were evaluated as a secondary step. RESULTS: The mean individual relative Constant-Murley score was 57.8+/-23.5% (1188%) in the surgical group. The mean Oxford Shoulder score was 34.8+/-10.6 (1046) points. Complications were recorded in 12 patients (60%). In the non-surgical group, the mean individual relative Constant-Murley score at 12 months from injury was 60.9+/-20.9% (1690%). The mean Oxford Shoulder score was 36.1+/-8.9 (1548) points. Complications were recorded in 4 patients (21.1%). CONCLUSIONS: In this study, surgical treatment patients with displaced 3- and 4-part proximal humerus fractures, mostly treated by angle-stable plates, showed a number of complications. Poor functional results of the surgical group were comparable to those of the non-surgical group. The indication for surgery, patient selection, type of surgery, surgical experience and subsequent rehabilitation should be carefully assessed for better results. KEY WORDS: proximal humerus fracture surgical treatment non-surgical treatment 3- and 4-part fractures. PMID- 27008168 TI - [Liver metastases from colon and rectal cancer in terms of differences in their clinical parameters]. AB - INTRODUCTION: From the clinical point of view, rectal cancer and colon cancer are clearly different nosological units in their progress and treatment. The aim of this study was to analyse and clarify the differences between the behaviour of liver metastases from colon and rectal cancer. The study of these factors is important for determining an accurate prognosis and indication of the most effective surgical therapy and oncologic treatment of colon and rectal cancer as a systemic disease. METHOD: 223 patients with metastatic disease of colorectal carcinoma operated at the Department of Surgery, University Hospital in Pilsen between January 1, 2006 and January 31, 2012 were included in our study. The group of patients comprised 145 men (65%) and 117 women (35%). 275 operations were performed. Resection was done in 177 patients and radiofrequency ablation (RFA) in the total of 98 cases. Our sample was divided into 3 categories according to the location of the primary tumor to C (colon), comprising 58 patients, S (c. sigmoideum) in 61 patients, and R (rectum), comprising 101 patients. Significance analysis of the studied factors (age, gender, staging [TNM classification], grading, presence of mucinous carcinoma, type of operation) was performed using ANOVA test. Overall survival (OS), disease-free interval (DFI) or no evidence of disease (NED) were estimated using Kaplan-Meier curves, which were compared with the log-rank and Wilcoxon tests. RESULTS: As regards the comparison of primary origin of colorectal metastases in liver regardless of their treatment (resection and RFA), our study indicated that rectal liver metastases showed a significantly earlier recurrence than colon liver metastases (shorter NED/DFI). Among other factors, a locally advanced finding, further R2 resection of liver metastases and positivity of lymph node metastases were statistically significant for the prognosis of an early recurrence of the primary colon and sigmoid tumor. Furthermore, we proved that in patients with primary rectal carcinoma, DFI (after the resection of liver metastases) was not influenced by the positivity of lymph node metastases of primary tumor or locally advanced primary tumor. The other factors studied (time from diagnosis of organ metastases to primary operation, grading, sex or age) were not shown to be statistically significant for the prognosis of OS and DFI (colorectal cancer in total). CONCLUSION: As proven by our study, rectal cancer and colon cancer are two different nosological units with specific prognostic factors with respect to their liver metastases. These differences have not been fully understood yet and require further exploration and classification based not only on histopathological, immunohistochemical and clinical factors, but also on molecular biological parameters. KEY WORDS: colon carcinoma metastases rectal carcinoma metastases prognostic factors overall survival - liver metastases. PMID- 27008169 TI - [Tissue cyanoacrylate glue in partial nephrectomy - our own experience and assessment]. AB - INTRODUCTION: The effect of cyanoacrylate glues was repeatedly evaluated in resections of liver, lungs and others organs, but minimally in kidney resection. The aim of our study was to evaluate the use of cyanoacrylate tissue glue in open and laparoscopic partial nephrectomy. METHOD: We evaluated a cohort of 32 patients who underwent partial nephrectomy with treatment of the resected area using cyanoacrylate glue. Laparoscopic resection was done in 23 patients, while 9 patients underwent an open procedure. Surgical results, complications and oncologic results were assessed. RESULTS: The median follow-up duration was 46 months. The mean time of open partial nephrectomy was 104 minutes and that of laparoscopic resection was 154 minutes; blood losses reached 250 ml and 184 ml, respectively. No serious complications occurred, and all patients survived the 3 year follow-up without any tumor recurrence. CONCLUSION: Hemostasis using the cyanoacrylate glue Glubran II was effective and safe. On the other hand, it increased the costs of the surgery and was not necessary.Key worlds: partial nephrectomy laparoscopic resection of kidney cyanoacrylate tissue glue. PMID- 27008170 TI - [Diagnosis and treatment of billiary ileus]. AB - INTRODUCTION: Biliary ileus represents only 14% of mechanical obstructions of the gastrointestinal tract. However, the rate of non-strangulated small bowel obstructions reaches as much as 25% in patients over 65 years of age. Usually, a pressure necrosis is created by a large gallstone that passes through the developed biliodigestive fistula, subsequently obturating the gastrointestinal tract. CASE REPORTS: 35 patients underwent a surgical procedure at the Department of Surgery, Teaching Hospital Pilsen for biliary ileus from January 1, 2000 to January 31, 2015. Mean age was 79 years (median 78 years; min. 58 years; max. 92 years). Aerobilia was visible in abdominal X-ray scans in 7 cases (26%) of 27 acquired images. Preoperatively, colonoscopy was done 2 times and esophagogastroduodenoscopy 9 times. Regarding surgical procedures, enterolithotomy was done in 21 cases, extraction of the gallstone from gastrotomy was done 3 times, small bowel resection 7 times, Hartmann resection 1 time, resection of ileoascendentoanastomosis 1 time, and extraction of the gallstone from duodenotomy with duodenojejunoanastomosis and cholecystectomy was done in 1 case. Ileotransversoanastomosis was performed in 1 case. Postoperative 30-day mortality was 14.3%. Postoperative morbidity according Clavien-Dindo was 22.8% for grade 1, 5.7% for grade 2, 11.5% for grade 3, and 11.5% for grade 4. A recurrence was observed in 8.8%. Primary treatment of the fistula and cholecystectomy were done in 1 case. CONCLUSION: The indication of primary biliodigestive fistula treatment always depends on the general condition of the patient and on the local finding in the gallbladder area. Residual fistula increases the risk of reccurence, but primary treatment is associated with higher mortality. It is also important to duly revise the entire bowel to avoid an early reccurence due to multiple gallstones. KEY WORDS: biliary ileus diagnosis treatment. PMID- 27008171 TI - [Total duodenopancreatectomy for renal cell carcinoma metastases - case report]. AB - INTRODUCTION: The frequency of pancreatic metastases ranges from 2% to 5%. Pancreas is an elective site for metastases from renal carcinoma. Pancreatic metastases from renal cell carcinoma are frequently the only metastatic site and they typically occur in the seventh decade of life. CASE REPORT: We report 1 female patient (aged 58 years) with multifocal and isolated pancreatic metastases of renal cell carcinoma. Total duodenopancreatectomy was performed. CONCLUSION: In selected cases, pancreatic resection due to renal cell cancer metastases is deemed indicated, improving overall patient survival. KEY WORDS: renal cell carcinoma (RCC) isolated pancreatic metastases total duodenopancreatectomy. PMID- 27008172 TI - [Castleman disease - unusual finding after operation of retroperitoneal tumor of young patient]. AB - Castleman disease is rare diagnosis. It was first mentioned in literature in 1954 by doctor Castleman and Lown. It is rare sickness which primary affects lymfatic nodes. There are four histo-morfologic subtypes and two clinic manifestations (uni and mulicentric). Comon clinical picture is simple lymfadenopathy of neck, medistinal a retroperitonal lymfatic nodes. Signs of this disease are heterogenic and depend on histological subtype. Also prognosis depends on type of illness. It should take place as benign diagnosis (unicentric form) but also can be potencionally malignant form which shlould exacerbate to malignant lymfoproliferation (multicentric form). Authors present the case of 29 years old men with clinical manifestation (jundice, intermitent bowel obstruction) of lagre retroperitoneal tumor in subhepatal localization. The treatment was radical surgical extirpation, surgery was without complications. Definitive histological diagnosis was confirmed as hyaline-vascular type of Castleman disease. Because the patient's clinical form was multicentric, he is now undergoing adjuvant oncological treatment. KEY WORDS: Castleman disease reproperitoneal tumor. PMID- 27008173 TI - Impact of pulse pressure on left ventricular global longitudinal strain in normotensive and newly diagnosed, untreated hypertensive patients. AB - OBJECTIVES: Little is known about the impact of pulse pressure on left ventricular systolic function. The aim of our study was to evaluate whether high pulse pressure is associated with subclinical left ventricular systolic dysfunction. METHODS: The study population included 143 participants (68 newly diagnosed, never-treated hypertensive, and 75 normotensive individuals) evaluated by echo-Doppler, including determination of global longitudinal strain (GLS) by speckle tracking. According to pulse pressure tertiles, participants were divided in two groups: the first group merging the first and second pulse pressure tertiles (n = 93, pulse pressure <55 mmHg) and the second group including the highest pulse pressure tertile (HPPT; n = 50, pulse pressure >=55 mmHg). RESULTS: The two groups were comparable for sex, BMI, and heart rate, whereas age was higher in individuals with the HPPT (P < 0.0001). Left ventricular mass index was significantly higher in individuals with the HPPT (P < 0.01), with no significant difference in relative wall thickness. Among several indices of left ventricular systolic function, only GLS was lower in individuals with the HPPT (P < 0.001). Transmitral E/A ratio (P = 0.006) was lower and E/e' ratio higher (P < 0.001) in the HPPT group. By a multilinear regression analysis, HPPT (P < 0.020) and overweight (P = 0.025) were independent correlates of low GLS. Replacing HPPT with the highest systolic blood pressure tertile, GLS was independently associated with BMI (P = 0.040), but not with the highest systolic blood pressure tertile (P = 0.069). CONCLUSION: Elevated pulse pressure negatively influences left ventricular longitudinal mechanics in a mixed population of normotensive and untreated hypertensive individuals. PMID- 27008174 TI - Anacardic Acids from Knema hookeriana as Modulators of Bcl-xL/Bak and Mcl-1/Bid Interactions. AB - Proteins of the Bcl-2 family are key targets in anticancer drug discovery. Disrupting the interaction between anti- and pro-apoptotic members of this protein family was the approach chosen in this study to restore apoptosis. Thus, a biological screening on the modulation of the Bcl-xL/Bak and Mcl-1/Bid interactions permitted the selection of Knema hookeriana for further phytochemical investigations. The ethyl acetate extract from the stem bark led to the isolation of six new compounds, three acetophenone derivatives (1-3) and three anacardic acid derivatives (4-6), along with four known anacardic acids (7 10) and two cardanols (11, 12). Their structures were elucidated by 1D and 2D NMR analysis in combination with HRMS experiments. The ability of these compounds to antagonize Bcl-xL/Bak and Mcl-1/Bid association was determined, using a protein protein interaction assay, but only anacardic acid derivatives (4-10) exhibited significant binding properties, with Ki values ranging from 0.2 to 18 MUM. Protein-ligand NMR experiments further revealed that anacardic acid 9, the most active compound, does not interact with the anti-apoptotic proteins Bcl-xL and Mcl-1 but instead interacts with pro-apoptotic protein Bid. PMID- 27008175 TI - What Do Children with Chronic Diseases and Their Parents Think About Pediatricians? A Qualitative Interview Study. AB - Objectives The aim of this study was to determine how pediatric patients and their parents perceive health care during hospital stays, what are their expectations of doctor behaviors, and which components of care do they consider to be the most important. Methods A qualitative descriptive study was carried out using the open interview technique. Twenty-six parents and 22 children undergoing hospital treatment participated. Results Our analysis identified two major themes: (1) doctor verbal and non-verbal behaviors, which included informing and explaining, conversations on topics other than the illness, tone of voice and other behaviors; and (2) perceived strategies used by doctors. This category included claims of doctors' intentional use of medical jargon to avoid addressing parental questions directly. Parents admitted that they did not understand medical vocabulary, but they also thought they might understand more of the medical issues if the doctor spoke using terms comprehensible to them. Conlcusions Our study shows the importance of interpersonal relationship affecting patient perception of quality of pediatric care. Parents of pediatric patients perceive that doctors behave in ways that deflect parents' questions and avoid providing them with medical information. Such behaviors include doctors excusing themselves by saying they are busy and using medical jargon. Medical students and doctors should be trained to communicate effectively with patients and their parents and develop skills to convey information in a simple and comprehensible way. PMID- 27008176 TI - Power, Politics, and Health: A New Public Health Practice Targeting the Root Causes of Health Equity. AB - Purpose Understanding the WHY, WHAT, and HOW of place-based work in maternal and child health (MCH) is critical to examining the components of the environment that shape health opportunity through the relationship between life expectancy and neighborhood residence. Description On September 18, 2014, during the CityMatCH Leadership and MCH Epidemiology Conference, Dr. Anthony Iton provided the Keynote Address focused on the root causes of health inequities. Assessment The address focused on issues of equity in California and initiatives designed to mitigate and prevent disparities, including the Bay Area Regional Health Equities Initiative framework. Dr. Iton presented information on how the framework translated into investment strategies and a policy and systems change approach to place-based work. Conclusion The field of MCH, because of its focus on supporting health during critical periods of development, is poised to play a significant role in reducing health inequities. Recognizing that human health suffers when low income communities are passive, disenfranchised and disorganized, in order to change this status quo, understanding that human capital is the greatest asset is the urgent challenge to the field of MCH. PMID- 27008177 TI - A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes. AB - Cullin-3 (CUL3)-based ubiquitin ligases regulate endosome maturation and trafficking of endocytic cargo to lysosomes in mammalian cells. Here, we report that these functions depend on SPOPL, a substrate-specific CUL3 adaptor. We find that SPOPL associates with endosomes and is required for both the formation of multivesicular bodies (MVBs) and the endocytic host cell entry of influenza A virus. In SPOPL-depleted cells, endosomes are enlarged and fail to acquire intraluminal vesicles (ILVs). We identify a critical substrate ubiquitinated by CUL3-SPOPL as EPS15, an endocytic adaptor that also associates with the ESCRT-0 complex members HRS and STAM on endosomes. Indeed, EPS15 is ubiquitinated in a SPOPL-dependent manner, and accumulates with HRS in cells lacking SPOPL. Together, our data indicates that a CUL3-SPOPL E3 ubiquitin ligase complex regulates endocytic trafficking and MVB formation by ubiquitinating and degrading EPS15 at endosomes, thereby influencing influenza A virus infection as well as degradation of EGFR and other EPS15 targets. PMID- 27008178 TI - Postnatal development of retrosplenial projections to the parahippocampal region of the rat. AB - The rat parahippocampal region (PHR) and retrosplenial cortex (RSC) are cortical areas important for spatial cognition. In PHR, head-direction cells are present before eye-opening, earliest detected in postnatal day (P)11 animals. Border cells have been recorded around eye-opening (P16), while grid cells do not obtain adult-like features until the fourth postnatal week. In view of these developmental time-lines, we aimed to explore when afferents originating in RSC arrive in PHR. To this end, we injected rats aged P0-P28 with anterograde tracers into RSC. First, we characterized the organization of RSC-PHR projections in postnatal rats and compared these results with data obtained in the adult. Second, we described the morphological development of axonal plexus in PHR. We conclude that the first arriving RSC-axons in PHR, present from P1 onwards, already show a topographical organization similar to that seen in adults, although the labeled plexus does not obtain adult-like densities until P12. PMID- 27008179 TI - PI(3,5)P2 biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms. AB - Proper development of the CNS axon-glia unit requires bi-directional communication between axons and oligodendrocytes (OLs). We show that the signaling lipid phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2] is required in neurons and in OLs for normal CNS myelination. In mice, mutations of Fig4, Pikfyve or Vac14, encoding key components of the PI(3,5)P2 biosynthetic complex, each lead to impaired OL maturation, severe CNS hypomyelination and delayed propagation of compound action potentials. Primary OLs deficient in Fig4 accumulate large LAMP1(+) and Rab7(+) vesicular structures and exhibit reduced membrane sheet expansion. PI(3,5)P2 deficiency leads to accumulation of myelin associated glycoprotein (MAG) in LAMP1(+)perinuclear vesicles that fail to migrate to the nascent myelin sheet. Live-cell imaging of OLs after genetic or pharmacological inhibition of PI(3,5)P2 synthesis revealed impaired trafficking of plasma membrane-derived MAG through the endolysosomal system in primary cells and brain tissue. Collectively, our studies identify PI(3,5)P2 as a key regulator of myelin membrane trafficking and myelinogenesis. PMID- 27008180 TI - Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration. AB - mTOR inhibition is beneficial in neurodegenerative disease models and its effects are often attributable to the modulation of autophagy and anti-apoptosis. Here, we report a neglected but important bioenergetic effect of mTOR inhibition in neurons. mTOR inhibition by rapamycin significantly preserves neuronal ATP levels, particularly when oxidative phosphorylation is impaired, such as in neurons treated with mitochondrial inhibitors, or in neurons derived from maternally inherited Leigh syndrome (MILS) patient iPS cells with ATP synthase deficiency. Rapamycin treatment significantly improves the resistance of MILS neurons to glutamate toxicity. Surprisingly, in mitochondrially defective neurons, but not neuroprogenitor cells, ribosomal S6 and S6 kinase phosphorylation increased over time, despite activation of AMPK, which is often linked to mTOR inhibition. A rapamycin-induced decrease in protein synthesis, a major energy-consuming process, may account for its ATP-saving effect. We propose that a mild reduction in protein synthesis may have the potential to treat mitochondria-related neurodegeneration. PMID- 27008181 TI - Behavioral training promotes multiple adaptive processes following acute hearing loss. AB - The brain possesses a remarkable capacity to compensate for changes in inputs resulting from a range of sensory impairments. Developmental studies of sound localization have shown that adaptation to asymmetric hearing loss can be achieved either by reinterpreting altered spatial cues or by relying more on those cues that remain intact. Adaptation to monaural deprivation in adulthood is also possible, but appears to lack such flexibility. Here we show, however, that appropriate behavioral training enables monaurally-deprived adult humans to exploit both of these adaptive processes. Moreover, cortical recordings in ferrets reared with asymmetric hearing loss suggest that these forms of plasticity have distinct neural substrates. An ability to adapt to asymmetric hearing loss using multiple adaptive processes is therefore shared by different species and may persist throughout the lifespan. This highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders. PMID- 27008182 TI - Erratum to: Estrogen receptor beta binds Sp1 and recruits a corepressor complex to the estrogen receptor alpha gene promoter. AB - Erratum to: Breast Cancer Res Treat (2012), 134:569-581, DOI 10.1007/s10549-012 2090-9. Uunfortunately, authors could not find the original film from which the figure was drawn. Therefore, as suggested by the Editor, they have repeated the relative experiment, and ask to publish this new figure as a correction. The authors apologize for any inconvenience that it may cause. PMID- 27008183 TI - Very low local recurrence rates after breast-conserving therapy: analysis of 8485 patients treated over a 28-year period. AB - The purpose of this study was to study the impact of changes in clinical practice on outcome in patients treated with breast-conserving therapy (BCT) over a period of 28 years. Patients with early invasive breast cancer, who were treated with BCT at the Netherlands Cancer Institute between 1980 and 2008, were studied. Clinical characteristics, treatment and outcome were compared between groups (1980-1987; 1988-1998; 1999-2008). The main endpoint analyzed was ipsilateral breast tumor recurrence (IBTR). 8485 patients with a median follow-up of 9 years (IQR 6-14 years) were analyzed. The cumulative 5- and 10-year IBTR incidences were, respectively, 2 and 5 % for the whole cohort and 4 and 9 % in patients <=40 years. Young age was a significant risk factor for IBTR in multivariable analysis. IBTR-free interval was better for patients who received a RT boost (HR 0.65) or systemic therapy (HR 0.52). In later years, patients less often received a boost and more often underwent adjuvant systemic treatment. 761 patients (9.0 %) underwent a re-excision; the tumor resection margins were tumor free for 85 %. In later years (1999-2008), 89 % of patients had a tumor-free margin. The margin status of invasive carcinoma did not influence IBTR, DM rate, or OS. Between 1980 and 2008, locoregional control after BCT remained stable with low IBTR rates, even in young patients. These good results were achieved under the policy of accepting close or focally positive margins, indicating this is a safe approach. The results of this study may help in lowering the re-excision rates, which are high in many centers. PMID- 27008184 TI - Safe P4 reagent in a reusable porous coordination network. AB - P4 generated from red phosphorus via the gas phase was trapped into an interactive pore of a porous coordination network, showing weak interactions which stabilize the reactive P4 in a pore. The network is reusable as a safe container of P4. Furthermore, we found a size dependence of the P4 trapping amount: for 100-50 MUm crystal, 27% occupancy of P4; and for <20 MUm crystal, ca. 93% occupancy of P4. PMID- 27008185 TI - New architectural design of delivery room reduces morbidity in preterm neonates: a prospective cohort study. AB - BACKGROUND: A multidisciplinary committee composed of a panel of experts, including a member of the American Academy of Pediatrics and American Institute of Architects, has suggested that the delivery room (DR) and the neonatal intensive care units (NICU) room should be directly interconnected. We aimed to investigate the impact of the architectural design of the DR and the NICU on neonatal outcome. METHODS: Two cohorts of preterm neonates born at < 32 weeks of gestational age, consecutively observed during 2 years, were compared prospectively before (Cohort 1: "conventional DR") and after architectural renovation of the DR realized in accordance with specific standards (Cohort 2: "new concept of DR"). In Cohort 1, neonates were initially cared for a conventional resuscitation area, situated in the DR, and then transferred to the NICU, located on a separate floor of the same hospital. In Cohort 2 neonates were assisted at birth directly in the NICU room, which was directly connected to the DR via a pass-through door. The primary outcome of the study was morbidity, defined by the proportion of neonates with at least one complication of prematurity (i.e., late-onset sepsis, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis). Secondary outcomes were mortality and duration of hospitalization. Statistical analysis was performed using standard methods by SPSS software. RESULTS: We enrolled 106 neonates (56 in Cohort 1 and 50 in Cohort 2). The main clinical and demographic characteristics of the 2 cohorts were similar. Moderate hypothermia (body temperature <= 35.9 degrees C) was more frequent in Cohort 1 (57%) compared with Cohort 2 (24%, p = 0.001). Morbidity was increased in Cohort 1 (73%) compared with Cohort 2 (44%, p = 0.002). No statistically significant differences in mortality and median duration of hospitalization were observed between the 2 cohorts of the study. CONCLUSIONS: If realized according to the proposed architectural standards, renovation of DR and NICU may represent an opportunity to reduce morbidity in preterm neonates. PMID- 27008186 TI - Programmable Self-Assembly of DNA-Protein Hybrid Hydrogel for Enzyme Encapsulation with Enhanced Biological Stability. AB - A DNA-protein hybrid hydrogel was constructed based on a programmable assembly approach, which served as a biomimetic physiologic matrix for efficient enzyme encapsulation. A dsDNA building block tailored with precise biotin residues was fabricated based on supersandwich hybridization, and then the addition of streptavidin triggered the formation of the DNA-protein hybrid hydrogel. The biocompatible hydrogel, which formed a flower-like porous structure that was 6.7 +/- 2.1 MUm in size, served as a reservoir system for enzyme encapsulation. Alcohol oxidase (AOx), which served as a representative enzyme, was encapsulated in the hybrid hydrogel using a synchronous assembly approach. The enzyme encapsulated hydrogel was utilized to extend the duration time for ethanol removal in serum plasma and the enzyme retained 78% activity after incubation with human serum for 24 h. The DNA-protein hybrid hydrogel can mediate the intact immobilization on a streptavidin-modified and positively charged substrate, which is very beneficial to solid-phase biosensing applications. The hydrogel encapsulated enzyme exhibited improved stability in the presence of various denaturants. For example, the encapsulated enzyme retained 60% activity after incubation at 55 degrees C for 30 min. The encapsulated enzyme also retains its total activity after five freeze-thaw cycles and even suspended in solution containing organic solvents. PMID- 27008187 TI - Usefulness of diagnostic laparoscopy with 5-aminolevulinic acid (ALA)-mediated photodynamic diagnosis for the detection of peritoneal micrometastasis in advanced gastric cancer after chemotherapy. AB - PURPOSE: Successful cases have shown that conversion surgery after chemotherapy improves the prognosis of advanced gastric cancer. However, it is necessary to carefully select patients who have no unresectable factors prior to surgery. We recently reported that diagnostic laparoscopy with photodynamic diagnosis using oral 5-aminolevulinic acid (ALA-PDD) is a promising tool for diagnosing early peritoneal metastasis in gastric cancer. We herein evaluated the usefulness of this technique for detecting peritoneal metastases of advanced gastric cancer after chemotherapy. METHODS: Diagnostic laparoscopy using sequential white light (WL) and ALA-PDD observations was performed in 38 patients with advanced gastric cancer after chemotherapy. The sensitivity of ALA-PDD for detecting peritoneal disease was compared with that of WL. The relationship between the state of peritoneal metastasis assessed by ALA-PDD and a cytological examination of the peritoneal fluid was evaluated. RESULTS: Twelve of the 38 patients (32 %) were diagnosed with peritoneal metastases by conventional laparoscopy. However, laparoscopy with ALA-PDD detected peritoneal metastases in 4 (11 %) of the 26 remaining patients. Three of these 4 patients had negative cytological results from the evaluation of the peritoneal fluid. CONCLUSIONS: Diagnostic laparoscopy using ALA-PDD is a useful technique for detecting metastases and determining treatment strategies to select patients with advanced gastric cancer who have received chemotherapy. PMID- 27008188 TI - High-resolution melting analysis (HRM) for differentiation of four major Taeniidae species in dogs Taenia hydatigena, Taenia multiceps, Taenia ovis, and Echinococcus granulosus sensu stricto. AB - Tapeworms of the genus Taenia include several species of important parasites with considerable medical and veterinary significance. Accurate identification of these species in dogs is the prerequisite of any prevention and control program. Here, we have applied an efficient method for differentiating four major Taeniid species in dogs, i.e., Taenia hydatigena, T. multiceps, T. ovis, and Echinococcus granulosus sensu stricto. High-resolution melting (HRM) analysis is simpler, less expensive, and faster technique than conventional DNA-based assays and enables us to detect PCR amplicons in a closed system. Metacestode samples were collected from local abattoirs from sheep. All the isolates had already been identified by PCR-sequencing, and their sequence data were deposited in the GenBank. Real-time PCR coupled with HRM analysis targeting mitochondrial cox1 and ITS1 genes was used to differentiate taeniid species. Distinct melting curves were obtained from ITS1 region enabling accurate differentiation of three Taenia species and E. granulosus in dogs. The HRM curves of Taenia species and E .granulosus were clearly separated at Tm of 85 to 87 degrees C. In addition, double-pick melting curves were produced in mixed infections. Cox1 melting curves were not decisive enough to distinguish four taeniids. In this work, the efficiency of HRM analysis to differentiate four major taeniid species in dogs has been demonstrated using ITS1 gene. PMID- 27008190 TI - Exploring the feasibility and acceptability of using tactical decision games to develop final year medical students' non-technical skills. AB - INTRODUCTION: Clinical decision-making, situation awareness, task management, and teamwork are key non-technical skills (NTS) required by junior doctors. Tactical decision games (TDGs) are low-fidelity classroom-based activities designed to develop proficiency in NTS. This study aimed to explore the feasibility and acceptability of using TDGs as a novel teaching method for final year medical students. METHODS: Final year medical students at the University of Edinburgh participated in a single TDG session. Focus groups were then used to explore students' perceptions of participating in the TDG session and transcribed data from the focus groups was thematically analyzed. RESULTS: Six key themes emerged from the data: "the value of non-medical games"; "giving and receiving feedback"; "observing and reflecting"; "recognizing and understanding NTS"; "dealing with uncertainty and ambiguity", and "introducing TDGs into the curriculum". CONCLUSIONS: TDGs are an easy-to-use, low-fidelity method of teaching medical students about the importance of NTS. Medical students view TDGs as a valuable learning activity that appears to increase awareness and understanding of the importance of NTS. PMID- 27008189 TI - First report of Filaria martis Gmelin, 1790 in the European mink, Mustela lutreola (Linnaeus, 1761). AB - The riparian European mink (Mustela lutreola), currently surviving in only three unconnected sites in Europe, is now listed as a critically endangered species according to the IUCN. Habitat loss and degradation, anthropic mortality, interaction with the feral American mink (Neovison vison), and infectious diseases are among the principal causes of its decline. Surveys of helminth parasites of this host that also include focus on subcutaneous potentially pathogenic helminths such as those belonging to the genus Filaria are very scarce. We report here the presence of specimens of Filaria martis in the subcutaneous connective tissues of three M. lutreola individuals from Spain. This is the first finding of a subcutaneous nematode in a representative of the genus Mustela. The report also enlarges the known range of the definitive hosts of this nematode. These worms were mainly located in the dorsal region of mink and more rarely in the knees, elbows, and hips. Skin sloughing was only observed in one M. lutreola with both septicaemia and an associated high burden of F. martis. Therefore, more attention should be paid to potentially pathogenic helminths when designing conservation programs dedicated to M. lutreola. PMID- 27008192 TI - Roles of cryo/thermal strength for redispersibility of drug nanocrystals: a representative study with andrographolide. AB - Due to limited understanding about the effect of cryo/thermal strength from drying process on the redispersibility of drug nanocrystals, the impact of the different type and concentration of stabilizers and matrix formers on the redispersibility of nanocrystals were systematically investigated. Andro nanosuspensions were transformed into Andro nanocrystals (Andro-NC) via different drying process. The results demonstrated that the redispersibility of Andro-NC at the aggressive cryo-strength (meant higher freezing rate) was more excellent than those at conservative and moderate condition. Compared to the thermal stress from drying, the employed amount and type of stabilizers more dramatically affected the redispersibility of Andro-NCP during lyophilization. The HPMC-sucrose and HPMC-sorbitol system achieved excellent performance that protected Andro-NC from crystal growth during lyophilization. During spray-drying, the impacts of types and amounts of stabilizers on the redispersibility of Andro-NCP were more significant compared to those induced by the thermal stress conditions. The polymers HPMC, PVPK30 and MCCS with high Tg played an outstanding role in preventing the Andro-NCP from breakage during spray-drying, due to the firmly steric barrier effect of polymeric stabilizers. It is concluded that Andro-NCP is subjected to agglomeration or crystal growth due to cryo/thermal stresses during drying. The polymeric stabilizers are more effective to protect Andro-NCP from the cryo/thermal damage during solidification process, which behaved strong surface adsorption and high glass transition property at different solidification stress. PMID- 27008191 TI - Flexible models for spike count data with both over- and under- dispersion. AB - A key observation in systems neuroscience is that neural responses vary, even in controlled settings where stimuli are held constant. Many statistical models assume that trial-to-trial spike count variability is Poisson, but there is considerable evidence that neurons can be substantially more or less variable than Poisson depending on the stimuli, attentional state, and brain area. Here we examine a set of spike count models based on the Conway-Maxwell-Poisson (COM Poisson) distribution that can flexibly account for both over- and under dispersion in spike count data. We illustrate applications of this noise model for Bayesian estimation of tuning curves and peri-stimulus time histograms. We find that COM-Poisson models with group/observation-level dispersion, where spike count variability is a function of time or stimulus, produce more accurate descriptions of spike counts compared to Poisson models as well as negative binomial models often used as alternatives. Since dispersion is one determinant of parameter standard errors, COM-Poisson models are also likely to yield more accurate model comparison. More generally, these methods provide a useful, model based framework for inferring both the mean and variability of neural responses. PMID- 27008193 TI - Parent Coping and the Behavioural and Social Outcomes of Children Diagnosed with Inherited Metabolic Disorders. AB - OBJECTIVE: To explore the level of coping and management of parents of children with inherited metabolic disorders (IMD) and the relationship with children's cognitive, behavioural and social functioning. METHODS: Parents of children (n = 22) with confirmed IMD (glutaric aciduria type I, methylmalonic aciduria, propionic aciduria, isovaleric aciduria, glycogen storage disease, maple syrup urine disease, ornithine transcarbamylase or very long-chain acyl-CoA dehydrogenase deficiency) completed standardised questionnaires regarding psychological distress, coping and family management. Children completed cognitive assessments and parents rated their behavioural and social functioning on standardised questionnaires. Scores were compared with normative data. RESULTS: Most parents were coping well; 4/22 reported high levels of psychological distress. Exploratory analysis found that parent coping variables were correlated to the child's internalising symptoms, whereas family management was related to children's externalising behaviours and social skills. No relationship was found between parent variables and cognitive functioning. CONCLUSIONS: Parental coping and family management impact on the child's internalising symptoms and externalising behaviours, respectively. Early identification of issues in these domains may enhance referral for therapeutic interventions and family support programmes. PMID- 27008194 TI - Sleep Disturbance, Obstructive Sleep Apnoea and Abnormal Periodic Leg Movements: Very Common Problems in Fabry Disease. AB - OBJECTIVES: To assess the prevalence of sleep disorder(s) in males with Fabry disease and explore possible association with disease phenotype. BACKGROUND: Fabry disease, an X-linked lysosomal storage disease caused by deficiency in alpha-galactosidase, results in intracellular accumulation of globotriaosylceramide. It causes organ dysfunction, most significantly affecting renal, cerebrovascular and cardiovascular systems. Respiratory involvement may include obstructive lung disease, reduced diffusing capacity and thickened soft and hard palates. Patients commonly develop small-fibre sensory peripheral neuropathy manifested by acroparaesthesia and pain crises. Combined with self reported sleep disturbance and snoring, these features suggest an increased risk of sleep disorders. METHODS: In-laboratory polysomnography (PSG) studies and sleep inventory assessments, including Epworth Sleepiness Scale (ESS), were performed in a cohort of male Fabry patients. PSGs were reviewed by a sleep physician. Sleep-disordered breathing and periodic leg movements were targeted for analysis. Associations with renal, cardiovascular and cerebrovascular function were sought. RESULTS: Twenty males underwent overnight PSG. Patient baseline characteristics included age 43.9 +/- 10.7 years, BMI 24.3 +/- 3.8 kg/m2, neck circumference 39.7 +/- 3.3 cm and ESS 9.8 +/- 5.1 (7/20, abnormal ESS >10). Abnormal periodic leg movement index (PLMI) was present in 95% (mean frequency 42.4 +/- 28.5/min) and sleep-disordered breathing in 50% patients. Periodic leg movements were associated with pain and depression but not with increased cortical arousal. CONCLUSIONS: Sleep-disordered breathing and abnormal PLMI are highly prevalent in patients with FD. The presence of abnormal PLMI alone appears to have minimal impact on sleep disturbance, but is associated with depression and analgesic requirement. PMID- 27008195 TI - Inherited Metabolic Disorders: Efficacy of Enzyme Assays on Dried Blood Spots for the Diagnosis of Lysosomal Storage Disorders. AB - High consanguinity rates, poor access to accurate diagnostic tests, and costly therapies are the main causes of increased burden of lysosomal storage disorders (LSDs) in developing countries. Therefore, there is a major unmet need for accurate and economical diagnostic tests to facilitate diagnosis and consideration of therapies before irreversible complications occur. In cross country study, we utilized dried blood spots (DBS) of 1,033 patients clinically suspected to harbor LSDs for enzymatic diagnosis using modified fluorometric assays from March 2013 through May 2015. Results were validated by demonstrating reproducibility, testing in different sample types (leukocytes/plasma/skin fibroblast), mutation study, or measuring specific biomarkers. Thirty percent (307/1,033) were confirmed to have one of the LSDs tested. Reference intervals established unambiguously identified affected patients. Correlation of DBS results with other biological samples (n = 172) and mutation studies (n = 74) demonstrated 100% concordance in Gaucher, Fabry, Tay Sachs, Sandhoff, Niemann Pick, GM1, Neuronal ceroid lipofuscinosis (NCL), Fucosidosis, Mannosidosis, Mucopolysaccharidosis (MPS) II, IIIb, IVa, VI, VII, and I-Cell diseases, and 91.4% and 88% concordance in Pompe and MPS-I, respectively. Gaucher and Pompe are the most common LSDs in India and Pakistan, followed by MPS-I in both India and Sri Lanka. Study demonstrates utility of DBS for reliable diagnosis of LSDs. Diagnostic accuracy (97.6%) confirms veracity of enzyme assays. Adoption of DBS will overcome significant hurdles in blood sample transportation from remote regions. DBS enzymatic and molecular diagnosis should become the standard of care for LSDs to make timely diagnosis, develop personalized treatment/monitoring plan, and facilitate genetic counseling. PMID- 27008196 TI - Adjoint multi-start-based estimation of cardiac hyperelastic material parameters using shear data. AB - Cardiac muscle tissue during relaxation is commonly modeled as a hyperelastic material with strongly nonlinear and anisotropic stress response. Adapting the behavior of such a model to experimental or patient data gives rise to a parameter estimation problem which involves a significant number of parameters. Gradient-based optimization algorithms provide a way to solve such nonlinear parameter estimation problems with relatively few iterations, but require the gradient of the objective functional with respect to the model parameters. This gradient has traditionally been obtained using finite differences, the calculation of which scales linearly with the number of model parameters, and introduces a differencing error. By using an automatically derived adjoint equation, we are able to calculate this gradient more efficiently, and with minimal implementation effort. We test this adjoint framework on a least squares fitting problem involving data from simple shear tests on cardiac tissue samples. A second challenge which arises in gradient-based optimization is the dependency of the algorithm on a suitable initial guess. We show how a multi-start procedure can alleviate this dependency. Finally, we provide estimates for the material parameters of the Holzapfel and Ogden strain energy law using finite element models together with experimental shear data. PMID- 27008198 TI - Design of Low Pt Concentration Electrocatalyst Surfaces with High Oxygen Reduction Reaction Activity Promoted by Formation of a Heterogeneous Interface between Pt and CeO(x) Nanowire. AB - Pt-CeO(x) nanowire (NW)/C electrocatalysts for the improvement of oxygen reduction reaction (ORR) activity on Pt were prepared by a combined process involving precipitation and coimpregnation. A low, 5 wt % Pt-loaded CeO(x) NW/C electrocatalyst, pretreated by an optimized electrochemical conditioning process, exhibited high ORR activity over a commercially available 20 wt % Pt/C electrocatalyst although the ORR activity observed for a 5 wt % Pt-loaded CeO(x) nanoparticle (NP)/C was similar to that of 20 wt % Pt/C. To investigate the role of a CeO(x) NW promotor on the enhancement of ORR activity on Pt, the Pt-CeO(x) NW interface was characterized by using hard X-ray photoelectron spectroscopy (HXPS), transmission electron microscopy (TEM), and electron energy loss spectroscopy (EELS). Microanalytical data obtained by these methods were discussed in relation to atomistic simulation performed on the interface structures. The combined techniques of HXPS, TEM-EELS, and atomistic simulation indicate that the Pt-CeO(x) NW interface in the electrocatalyst contains two different defect clusters: Frenkel defect clusters (i.e., 2Pt(i)(**) - 4O(i)" - 4V(o)(**) - V(Ce)"") formed in the surface around the Pt-CeO(x) NW interface and Schottky defect clusters (i.e., (Pt(Ce)" - 2V(O)(**) - 2Ce(Ce)') and (Pt(Ce)" - V(O)(**))) which appear in the bulk of the Pt-CeO(x) NW interface similarly to Pt CeO(x) NP/C. It is concluded that the formation of both Frenkel defect clusters and Schottky defect clusters at the Pt-CeO(x) NW heterointerface contributes to the promotion of ORR activity and permits the use of lower Pt-loadings in these electrocatalysts. PMID- 27008197 TI - In silico coronary wave intensity analysis: application of an integrated one dimensional and poromechanical model of cardiac perfusion. AB - Coronary wave intensity analysis (cWIA) is a diagnostic technique based on invasive measurement of coronary pressure and velocity waveforms. The theory of WIA allows the forward- and backward-propagating coronary waves to be separated and attributed to their origin and timing, thus serving as a sensitive and specific cardiac functional indicator. In recent years, an increasing number of clinical studies have begun to establish associations between changes in specific waves and various diseases of myocardium and perfusion. These studies are, however, currently confined to a trial-and-error approach and are subject to technological limitations which may confound accurate interpretations. In this work, we have developed a biophysically based cardiac perfusion model which incorporates full ventricular-aortic-coronary coupling. This was achieved by integrating our previous work on one-dimensional modelling of vascular flow and poroelastic perfusion within an active myocardial mechanics framework. Extensive parameterisation was performed, yielding a close agreement with physiological levels of global coronary and myocardial function as well as experimentally observed cumulative wave intensity magnitudes. Results indicate a strong dependence of the backward suction wave on QRS duration and vascular resistance, the forward pushing wave on the rate of myocyte tension development, and the late forward pushing wave on the aortic valve dynamics. These findings are not only consistent with experimental observations, but offer a greater specificity to the wave-originating mechanisms, thus demonstrating the value of the integrated model as a tool for clinical investigation. PMID- 27008200 TI - Shutting off inflammation: A novel switch on hepatic stellate cells. PMID- 27008201 TI - A nationwide survey of hepatitis E viral infection in French blood donors. AB - Most cases of hepatitis E viral (HEV) infection in developed countries are autochthonous. Nevertheless, the reported seroprevalence of HEV varies greatly depending on the geographical area and the performance of the immunoassay used. We used validated assays to determine the prevalence of anti-HEV immunoglobulin G (IgG) and IgM among 10,569 French blood donors living in mainland France and three overseas areas. Epidemiological information was collected using a specific questionnaire. We found an overall IgG seroprevalence of 22.4% (8%-86.4%) depending on the geographical area (P < 0.001). The presence of anti-HEV IgG was associated with increasing age (P < 0.001) and eating pork meat (P = 0.03), pork liver sausages (P < 0.001), game meat (P < 0.01), offal (P < 0.001), and oysters (P = 0.02). Conversely, drinking bottled water was associated with a lower rate of anti-HEV IgG (P = 0.02). Overall IgM seroprevalence was 1% (0%-4.6%). The frequency of anti-HEV IgM was higher in donors living in a high anti-HEV IgG seroprevalence area (1.9% versus 0.7%, P < 0.001) and in those eating pork liver sausage (1.4% versus 0.7%, P < 0.01), pate (1% versus 0.4, P = 0.04), and wild boar (1.3% versus 0.7%, P < 0.01). CONCLUSION: HEV is endemic in France and hyperendemic in some areas; eating habits alone cannot totally explain the exposure to HEV, and contaminated water could contribute to the epidemiology of HEV infection in France. PMID- 27008202 TI - Correction: Up-regulation of histone methyltransferase SETDB1 by multiple mechanisms in hepatocellular carcinoma promotes cancer metastasis. PMID- 27008203 TI - Correction. PMID- 27008204 TI - Ruptured blebs and racing hearts: autonomic cardiac changes in neurosurgeons during microsurgical clipping of aneurysms. AB - INTRODUCTION: In this study, we intend to evaluate the autonomic changes occurring in neurosurgeons and thus the stress during microsurgical clipping of aneurysms. AIMS AND OBJECTIVES: The aim of the current study is to evaluate the heart rate variability (HRV) of the neurosurgeons during microsurgical clipping of aneurysm by using continuous real time monitoring of the ECG intraoperatively. MATERIAL AND METHODS: Lead II ECG was recorded using Bioharness((r)) (Zephyr Technologies, Annapolis, MD) in 4 healthy neurosurgeons who performed 29 microsurgical clipping of aneurysms. ECG from 21 surgeries was analysed (LabChart((r)) software, ADInstruments, Dunedin, New Zealand) across five stages: Baseline (BL), sylvian fissure dissection (SFD), perianeurysmal dissection (PAD), clipping of the aneurysm (CLIP) and haemostasis (HEMO). RESULTS: There was a reduction in TP and an increased LF/HF ratio in spite of suppression of both LF and HF powers. Contrary to the common understanding that the sympathetic limb of the autonomic system mostly mediates responses during stress and anxiety, we found that there was a significant contribution of the parasympathetic system too. PMID- 27008205 TI - Prostate cancer: from Gleason scoring to prognostic grade grouping. AB - The Gleason grading system was developed in the late 1960s by Dr. Donald F. Gleason. Due to changes in prostatic adenocarcinoma (PAC) detection and treatment, newer technologies to better characterize prostatic pathology, subsequently described variants of PAC and further data relating various morphologic patterns to prognosis, the application of the Gleason grading system changed substantially in surgical pathology. First in 2005 and more recently in 2014, consensus conferences were held to update PAC grading. Here, we review of the successive changes in the grading of PAC from the original system, with emphasis on the newest prognostic grade grouping. PMID- 27008206 TI - Thermal Processing of Silicones for Green, Scalable, and Healable Superhydrophobic Coatings. AB - The thermal degradation of silicones is exploited and engineered to make super hydrophobic coatings that are scalable, healable, and ecofriendly for various outdoor applications. The coatings can be generated and regenerated at the rate of 1 m(2) min(-1) using premixed flames, adhere to a variety of substrates, and tolerate foot traffic (>1000 steps) after moderate wear and healing. PMID- 27008207 TI - Relationship between body mass index and functional recovery in stroke rehabilitation setting. PMID- 27008208 TI - Precise image-guided irradiation of small animals: a flexible non-profit platform. AB - Preclinical in vivo studies using small animals are essential to develop new therapeutic options in radiation oncology. Of particular interest are orthotopic tumour models, which better reflect the clinical situation in terms of growth patterns and microenvironmental parameters of the tumour as well as the interplay of tumours with the surrounding normal tissues. Such orthotopic models increase the technical demands and the complexity of preclinical studies as local irradiation with therapeutically relevant doses requires image-guided target localisation and accurate beam application. Moreover, advanced imaging techniques are needed for monitoring treatment outcome. We present a novel small animal image-guided radiation therapy (SAIGRT) system, which allows for precise and accurate, conformal irradiation and x-ray imaging of small animals. High accuracy is achieved by its robust construction, the precise movement of its components and a fast high-resolution flat-panel detector. Field forming and x-ray imaging is accomplished close to the animal resulting in a small penumbra and a high image quality. Feasibility for irradiating orthotopic models has been proven using lung tumour and glioblastoma models in mice. The SAIGRT system provides a flexible, non-profit academic research platform which can be adapted to specific experimental needs and therefore enables systematic preclinical trials in multicentre research networks. PMID- 27008210 TI - Ruthenium-Catalyzed Hydroarylation and One-Pot Twofold Unsymmetrical C-H Functionalization of Arenes. AB - A methyl phenyl sulfoximine (MPS) is used as a directing group in the ruthenium catalyzed intramolecular hydroarylation of alkene-tethered benzoic acid derivatives to afford dihydrobenzofurans and indolines in good to excellent yields. A one-pot, unsymmetrical, twofold C-H functionalization involving intramolecular C-C and intermolecular C-C/C-N bond formations is successfully demonstrated by using a single set of catalytic reaction conditions, which is unprecedented thus far. A novel isoquinolone-bearing dihydrobenzofuran is constructed through an unsymmetrical twofold C-H functionalization. PMID- 27008209 TI - Exploring Sources of Emotional Distress among People Living with Scleroderma: A Focus Group Study. AB - BACKGROUND: Systemic sclerosis, or scleroderma, is a chronic and rare connective tissue disease with negative physical and psychological implications. Sources of emotional distress and the impact they have on the lives of people with scleroderma are not well understood. OBJECTIVES: To gain an in-depth understanding of the emotional experiences and sources of emotional distress for women and men living with scleroderma through focus group discussions. METHODS: Three semi-structured focus group discussions were conducted (two in English, one in French) with a total of 22 people with scleroderma recruited through the Scleroderma Society of Ontario in Hamilton, Ontario and a scleroderma clinic in Montreal, Canada. Interviews were recorded, transcribed, and then coded for emerging themes using thematic inductive analysis. RESULTS: Core themes representing sources of emotional distress were identified, including: (a) facing a new reality; (b) the daily struggle of living with scleroderma; (c) handling work, employment and general financial burden; (d) changing family roles; (e) social interactions; and (f) navigating the health care system. Collectively, these themes refer to the stressful journey of living with scleroderma including the obstacles faced and the emotional experiences beginning prior to receiving a diagnosis and continuing throughout the participants' lives. CONCLUSION: Scleroderma was portrayed as being an unpredictable and overwhelming disease, resulting in many individuals experiencing multiple sources of emotional distress. Interventions and supportive resources need to be developed to help individuals with scleroderma and people close to them manage and cope with the emotional aspects of the disease. PMID- 27008211 TI - Texture- and deformability-based surface recognition by tactile image analysis. AB - Deformability and texture are two unique object characteristics which are essential for appropriate surface recognition by tactile exploration. Tactile sensation is required to be incorporated in artificial arms for rehabilitative and other human-computer interface applications to achieve efficient and human like manoeuvring. To accomplish the same, surface recognition by tactile data analysis is one of the prerequisites. The aim of this work is to develop effective technique for identification of various surfaces based on deformability and texture by analysing tactile images which are obtained during dynamic exploration of the item by artificial arms whose gripper is fitted with tactile sensors. Tactile data have been acquired, while human beings as well as a robot hand fitted with tactile sensors explored the objects. The tactile images are pre processed, and relevant features are extracted from the tactile images. These features are provided as input to the variants of support vector machine (SVM), linear discriminant analysis and k-nearest neighbour (kNN) for classification. Based on deformability, six household surfaces are recognized from their corresponding tactile images. Moreover, based on texture five surfaces of daily use are classified. The method adopted in the former two cases has also been applied for deformability- and texture-based recognition of four biomembranes, i.e. membranes prepared from biomaterials which can be used for various applications such as drug delivery and implants. Linear SVM performed best for recognizing surface deformability with an accuracy of 83 % in 82.60 ms, whereas kNN classifier recognizes surfaces of daily use having different textures with an accuracy of 89 % in 54.25 ms and SVM with radial basis function kernel recognizes biomembranes with an accuracy of 78 % in 53.35 ms. The classifiers are observed to generalize well on the unseen test datasets with very high performance to achieve efficient material recognition based on its deformability and texture. PMID- 27008212 TI - Regulation of the intestinal tight junction by natural polyphenols: A mechanistic perspective. AB - Impairment of the epithelial barrier function is closely linked to the pathogenesis of various gastrointestinal diseases, food allergies, type I diabetes, and other systematic diseases. Plant-derived polyphenols are natural secondary metabolites and exert various physiological benefits, including anti inflammatory, anti-oxidative, anti-carcinogenic, and anti-aging effects. Recent studies also show the role of plant polyphenols in regulation of the intestinal barrier and prevention of intestinal inflammatory diseases. Here we summarize the regulatory pathways and mediators linking polyphenols to their beneficial effects on tight junction and gut epithelial barrier functions, and provide useful information about using polyphenols as nutraceuticals for intestinal diseases. PMID- 27008213 TI - What's in a Name? Effect of Breed Perceptions & Labeling on Attractiveness, Adoptions & Length of Stay for Pit-Bull-Type Dogs. AB - Previous research has indicated that certain breeds of dogs stay longer in shelters than others. However, exactly how breed perception and identification influences potential adopters' decisions remains unclear. Current dog breed identification practices in animal shelters are often based upon information supplied by the relinquishing owner, or staff determination based on the dog's phenotype. However, discrepancies have been found between breed identification as typically assessed by welfare agencies and the outcome of DNA analysis. In Study 1, the perceived behavioral and adoptability characteristics of a pit-bull-type dog were compared with those of a Labrador Retriever and Border Collie. How the addition of a human handler influenced those perceptions was also assessed. In Study 2, lengths of stay and perceived attractiveness of dogs that were labeled as pit bull breeds were compared to dogs that were phenotypically similar but were labeled as another breed at an animal shelter. The latter dogs were called "lookalikes." In Study 3, we compared perceived attractiveness in video recordings of pit-bull-type dogs and lookalikes with and without breed labels. Lastly, data from an animal shelter that ceased applying breed labeling on kennels were analyzed, and lengths of stay and outcomes for all dog breeds, including pit bulls, before and after the change in labeling practice were compared. In total, these findings suggest that breed labeling influences potential adopters' perceptions and decision-making. Given the inherent complexity of breed assignment based on morphology coupled with negative breed perceptions, removing breed labels is a relatively low-cost strategy that will likely improve outcomes for dogs in animal shelters. PMID- 27008214 TI - [Importance of revision- and tumor-endoprosthetics in the treatment of periprosthetic fractures of the lower extremity]. AB - Periprosthetic fractures of hip and knee prostheses are gaining clinical significance due to the increasing numbers of of primary arthroplasties. Additionally, these fractures are often associated with poor bone quality or present in patients after multiple revision procedures and concomitant excessive bone defects precluding those patients to be adequately treated by conventional osteosynthesis. Revision implants provide a wide range of options for the treatment of these fractures in order to achieve good clinical results. In the acetabular region cavitary defects associated with periprosthetic fractures can be treated by the use of megacups. Extensive segmental defects and pelvic discontinuity necessitate the use of cups with additional iliac support or even customized implants. Proximal femoral fractures can usually be fixed with modular stems and diaphyseal anchorage. Periprosthetic knee joint fractures can be treated with revision implants with modular sleeves or augment-combinations allowing sufficient bridging of bony defects. Functional reconstruction or refixation of the extensor mechanism is of crucial importance. PMID- 27008215 TI - [Periprosthetic humeral fractures: Strategies and techniques for osteosynthesis]. AB - The prevalence of periprosthetic humeral fractures (PHF) is currently low and accounts for 0.6-2.4%. Due to an increase in the rate of primary implantations a quantitative increase of PHF is to be expected in the near future. The majority of PHF occur intraoperatively during implantation with an increased risk for cementless stems and when performing total arthroplasty. Additional risk factors are in particular female gender and the severity of comorbidities. In contrast, postoperative PHF mostly due to low-energy falls, have a prevalence between 0.6% and 0.9% and are significantly less common. The prognosis and functional outcome following revision by open reduction internal fixation (ORIF) essentially depend on a thorough assessment of the indications for revision surgery, the operative treatment and the pretraumatic functional condition of the affected shoulder. In the armamentarium of periprosthetic ORIF of the humerus cerclage systems and locking implants as well as a combination of both play a central role. In comminuted fractures with extensive defect zones, severely thinned cortex or extensive osteolysis a biological augmentation of the ORIF should be considered. In this context when the indications are correctly interpreted, especially in the case of a stable anchored stem, various groups have reported that a high bony union rate can be achieved. As the treatment of PHF is complex it should be performed in dedicated centers in order to adequately address potential comorbidities, especially in the elderly population. PMID- 27008216 TI - [Injuries under the influence of alcohol]. AB - BACKGROUND: In Germany, an average of 9.5 L of pure alcohol is consumed per capita per year. Alcohol is known to negatively influence psychomotor abilities. The aim of this study was to evaluate injuries that lead to hospital admission with and without prior intake of alcohol. PATIENTS AND METHODS: Over a 7-month period, all 1317 patients who were admitted to the hospital because of an injury were evaluated with respect to their blood-alcohol level. Patient data of both groups (139 injuries under alcohol influence and 1178 injuries without alcohol influence) were compared with respect to the mechanism and type of injury, patient demographics, and treatment costs. RESULTS: At the time of presentation, 11 % (n = 139) of all admitted patients had detectable blood-alcohol levels of more than 0.1 g/L with an average blood-alcohol level of 2.21 g/L. Female patients had an average of 1.96 g/L and males an average of 2.28 g/L (N.S.). Almost every fifth male patient (109 out of 570, 19 %) had a detectable blood alcohol level, compared to only 4 % of all admitted female patients. Among the patients admitted between 11:00 p.m. and 5:00 a.m., 35 % had detectable blood alcohol levels and among the 20- to 30-year-old patients, 24 % had detectable blood-alcohol levels. The leading mechanisms of injury among intoxicated patients were falls (50 %, n = 70) and physical violence (18 %, n = 25). The latter was recorded significantly (p = 0.01) less among sober patients (0.17 %, n = 2). The most frequent diagnosis was a mild concussion in both intoxicated (60%, n = 84) and sober (34 %, n = 402) patients (p = 0.04). The time to discharge averaged 4.3 days for intoxicated and 5.6 days for sober patients. CONCLUSIONS: Injuries that occur while under the influence of alcohol that lead to hospital admission are particularly frequent in male patients aged between 20 and 30 years. They do not necessarily lead to more severe injuries. PMID- 27008217 TI - 2015 ISSVD, ISSWSH and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia. AB - INTRODUCTION: In 2014, the executive council of the International Society for the Study of Vulvovaginal Disease, the boards of directors of the International Society for the Study of Women's Sexual Health, and the International Pelvic Pain Society acknowledged the need to revise the current terminology of vulvar pain, on the basis of the significant increase in high-quality etiologic studies published in the last decade. MATERIALS AND METHODS: The new terminology was achieved in the following 4 steps. The first involved a terminology consensus conference with representatives of the 3 societies, held in April 2015. Then, an analysis of the relevant published studies was used to establish a level of evidence for each factor associated with vulvodynia. The terminology was amended on the basis of feedback from members of the societies. Finally, each society's board accepted the new terminology. RESULTS AND CONCLUSIONS: In 2015,the International Society for the Study of Vulvovaginal Disease, International Society for the Study of Women's Sexual Health, and International Pelvic Pain Society adopted a new vulvar pain and vulvodynia terminology that acknowledges the complexity of the clinical presentation and pathophysiology involved in vulvar pain and vulvodynia, and incorporates new information derived from evidence-based studies conducted since the last terminology published in 2003. PMID- 27008218 TI - Racial and Ethnic Disparities in Hospital Readmissions After Delivery. PMID- 27008219 TI - Racial and Ethnic Disparities in Hospital Readmissions After Delivery. PMID- 27008220 TI - In Reply. PMID- 27008221 TI - Changing the Diagnostic Criteria for Gestational Diabetes Mellitus?: Gestational Diabetes Screening: The International Association of the Diabetes and Pregnancy Study Groups Compared With Carpenter-Coustan Screening. PMID- 27008222 TI - In Reply. PMID- 27008223 TI - Trends in Stillbirth by Gestational Age in the United States, 2006-2012. PMID- 27008224 TI - A Multi-State Analysis of Early-Term Delivery Trends and the Association With Term Stillbirth Trends in Stillbirth by Gestational Age in the United States, 2006-2012 Stillbirth and the 39-Week Rule: Can We Be Reassured? PMID- 27008225 TI - A Multi-State Analysis of Early-Term Delivery Trends and the Association With Term Stillbirth Trends in Stillbirth by Gestational Age in the United States, 2006-2012 Stillbirth and the 39-Week Rule: Can We Be Reassured? PMID- 27008226 TI - In Reply. PMID- 27008227 TI - In Reply. PMID- 27008228 TI - In Reply. PMID- 27008229 TI - Editor's Note. PMID- 27008235 TI - Committee Opinion No. 661: Integrating Immunizations Into Practice. AB - Immunization against vaccine-preventable diseases is an essential component of women's primary and preventive health care. Despite the importance of vaccination and clear guidance from public health agencies, rates of vaccination lag behind national goals. Obstetrician-gynecologists can play a major role in reducing morbidity and mortality from a range of vaccine-preventable diseases, including pertussis, influenza, human papillomavirus, and hepatitis. Given demonstrated vaccine efficacy and safety, and the large potential for prevention of many infectious diseases that affect adults, pregnant women, and newborns, obstetrician-gynecologists should include immunizations as an integral part of their practice. To do so, they must embrace their role as important sources of information and advice on immunization for adults, adolescents, and pregnant women, and advance their patients' well-being with continued efforts to augment immunization services in their offices. Increasing awareness combined with the many suggestions in this document will work to enhance immunization uptake. PMID- 27008236 TI - Headache and Facial Swelling. PMID- 27008237 TI - Erratum to: New Patient-Oriented Tools for Assessing Atrophic Acne Scarring. PMID- 27008238 TI - Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats. AB - BACKGROUND: Folates play an important role to prevent neurological disorders in embryo development and in cardiovascular diseases. Folate supplementation is suggested, particularly in females of childbearing age, for the prevention of embryonal NTDs during pregnancy. Folic acid and reduced folate ((6S)5-MTHF) are currently used in supplementation. The aim of this study was to compare the bioavailability of Quatrefolic(r), a novel patented (6S)5-MTHF glucosamine salt, with (6S)5-MTHF calcium salt and folic acid in Sprague Dawley rats. METHODS: Fifty-four to fifty-five-day old male Sprague-Dawley rats were divided in 3 treatment groups, each comprising 6 animals, receiving folic acid, (6S)5-MTHF calcium salt or Quatrefolic(r) at the dose of 70 ug/kg of (6S)5-MTHF equivalents in a single oral administration. Folates were determined in plasma with a HPLC method employing fluorimetric detection. (6S)5-MTHF level was chosen as a convenient end point to evaluate folate absorption. The main pharmacokinetic parameters were calculated (Cmax, tmax, AUC). RESULTS: Quatrefolic(r) administration produced a plasmatic (6S)5-MTHF concentration peak (Cmax: 879.6+/ 330.3 ng/mL) 1.8 times higher than (6S)5-MTHF Ca salt (486.8+/-184.1 ng/mL), and 3.1 times higher than folic acid supplementation (281.5+/-135.7 ng/mL), while tmax values were similar for the three folate forms. Quatrefolic(r) supplementation showed AUC8h (1123.9 ng/mL ? h) 9.7 times higher than folic acid (114.7 ng/mL ? h) and 1.12 times higher than (6S)5-MTHF Ca salt (997.6 ng/mL ? h). CONCLUSIONS: Quatrefolic(r) has demonstrated an enhanced oral bioavailability in comparison to other reduced folates and to folic acid in rats. PMID- 27008239 TI - Delivery after external cephalic version, is there an increased rate of cesarian section? AB - BACKGROUND: The aim of this study was to compare the obstetric outcomes after successful external cephalic version (cases) with a group of pregnant women with a spontaneous cephalic fetal position at delivery (controls). METHODS: Retrospective review of the cohort of study was performed at the University Hospital of Getafe (Madrid, Spain) between January 2012 and January 2013. SAMPLE POPULATION: 1516 patients (48 cases; 1468 controls). We compared the type of delivery in pregnant women after ECV performed successfully (cases) with spontaneous cephalic presentations (controls). Pregnancies with vaginal delivery contraindicated, elective cesarean section (CS) justified by maternal disease, multiple pregnancies, or pregnancies below 37 weeks were excluded. Maternal age, BMI, parity, gestational age at delivery, and onset of labor (spontaneous or induced) were controlled. RESULTS: Prevalence of CS and operative delivery in both groups. Women who underwent a successful ECV had a significantly higher CS rate compared with the women of the control group (12/48 [25%] vs. 202/1468 [13.76%]; P=0.028). There was no difference in the rate of operative delivery (6/48 [12.5%] vs. 177/1468 [12.05%] P=0.92). CONCLUSIONS: Deliveries following a successful ECV are associated with an increased CS rate compared with deliveries of fetuses with spontaneous cephalic presentations. PMID- 27008240 TI - Office hysteroscopy: an update. PMID- 27008241 TI - Procedures of cervical conization: a national survey among Italian colposcopy units. AB - BACKGROUND: The recent evolution of surgical techniques, anesthesia and treatment strategies has led to a decrease in the number of cervical conization procedures performed in ordinary hospitalization or with anesthetics other than local infiltration anesthesia of the cervix. Conization should be as least invasive as possible, favor women's compliance and resumption of normal daily activities after surgery. We evaluated various aspects of patient care revolving around conization (technical, healthcare, and administrative aspects) in the clinical practice of 26 Italian colposcopy units. METHODS: A standard multiple-choice questionnaire was used. The retrospective study covered a period of 10 years. RESULTS: The overall number of conization procedures performed over the 10 years' observation period ranged from 20,000 to 37,500. The techniques used were the loop electrosurgical excision procedure in 79.9% of cases, CO2 laser in 16.7%, and the cold-knife biopsy in 3.4%. An outpatient regimen was reported in 62.1% of cases, a day-surgery regimen in 35.2% and an ordinary hospitalization in 2.7%. Local anesthesia, deep sedation and general anesthesia were usually performed in 86.7%, 11.9% and in 1.4% of cases, respectively. The use of prophylactic antibiotics was common only in 8% of cases. The rate of major adverse events recorded over the observed period varied between 0.04% and 0.02% (15,000-29,000 conizations). CONCLUSIONS: The administrative regimen in which conizations are performed is an expression of behaviors of different health authorities and hospitals in relation to the costs that this procedure entails. PMID- 27008242 TI - A Highly Selective Chemosensor for Cyanide Derived from a Formyl-Functionalized Phosphorescent Iridium(III) Complex. AB - A new phosphorescent iridium(III) complex, bis[2',6'-difluorophenyl-4 formylpyridinato-N,C4']iridium(III) (picolinate) (IrC), was synthesized, fully characterized by various spectroscopic techniques, and utilized for the detection of CN(-) on the basis of the widely known hypothesis of the formation of cyanohydrins. The solid-state structure of the developed IrC was authenticated by single-crystal X-ray diffraction. Notably, the iridium(III) complex exhibits intense red phosphorescence in the solid state at 298 K (PhiPL = 0.16) and faint emission in acetonitrile solution (PhiPL = 0.02). The cyanide anion binding properties with IrC in pure and aqueous acetonitrile solutions were systematically investigated using two different channels: i.e., by means of UV vis absorption and photoluminescence. The addition of 2.0 equiv of cyanide to a solution of the iridium(III) complex in acetonitrile (c = 20 MUM) visibly changes the color from orange to yellow. On the other hand, the PL intensity of IrC at 480 nm was dramatically enhanced ~5.36 * 10(2)-fold within 100 s along with a strong signature of a blue shift of the emission by ~155 nm with a detection limit of 2.16 * 10(-8) M. The cyanohydrin formation mechanism is further supported by results of a (1)H NMR titration of IrC with CN(-). As an integral part of this work, phosphorescent test strips have been constructed by impregnating Whatman filter paper with IrC for the trace detection of CN(-) in the contact mode, exhibiting a detection limit at the nanogram level (~265 ng/mL). Finally, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were performed to understand the electronic structure and the corresponding transitions involved in the designed phosphorescent iridium(III) complex probe and its cyanide adduct. PMID- 27008243 TI - Towards the system-wide implementation of the International Classification of Functioning, Disability and Health in routine practice: Lessons from a pilot study in China. AB - In 2011 the Chinese leadership in rehabilitation, in collaboration with the International Classification of Functioning, Disability and Health (ICF) Research Branch, embarked on an effort towards the system-wide implementation of the ICF in the healthcare system in China. We report here on the lessons learned from the pilot phase of testing the ICF Generic Set, a parsimonious set of 7 ICF categories, which have been shown to best describe functioning across the general population and people with various health conditions, for use in routine clinical practice in China. The paper discusses whether classification and measurement are compatible, what number of ICF categories should be included in data collection in routine practice, and the usefulness of a functioning profile and functioning score in clinical practice and health research planning. In addition, the paper reflects on the use of ICF qualifiers in a rating scale and the particularities of certain ICF categories contained in the ICF Generic Set when used as items in the context of Chinese rehabilitation and healthcare. Finally, the steps required to enhance the utility of system-wide implementation of the ICF in rehabilitation and healthcare services are set out. PMID- 27008244 TI - Neurobehavioral Disturbances During Acute and Early HIV Infection. AB - BACKGROUND AND OBJECTIVE: Acute and early human immunodeficiency virus infection (AEH) is accompanied by neuroinflammatory processes as well as impairment in neurocognitive and everyday functions, but little is known about the frequency and clinical correlates of the neurobehavioral disturbances during this period. We compared pre-seroconversion with current levels of apathy, disinhibition, and executive dysfunction; we also examined everyday function and HIV disease correlates of neuropsychiatric impairment in individuals with AEH. METHODS: In this study, 34 individuals with AEH and 39 HIV-seronegative participants completed neuromedical and neuropsychological assessments, a structured psychiatric interview, and the apathy, disinhibition, and executive dysfunction subscales of the Frontal Systems Behavioral Scale. RESULTS: Independent of any substance use and mood disorders, the AEH group had significantly higher levels of current apathy and executive dysfunction than the controls, but not greater disinhibition. Retrospective ratings of pre-seroconversion levels of apathy, disinhibition, and executive dysfunction were all higher in the AEH group than the controls. After seroconversion, the AEH cohort had increases in current apathy and executive dysfunction, but not disinhibition. In the AEH cohort, higher current global neurobehavioral dysfunction was significantly associated with lower nadir CD4 counts, slowed information processing speed, and more everyday function problems. CONCLUSIONS: These data suggest that individuals who have recently acquired HIV experienced higher-than-normal premorbid levels of neurobehavioral disturbance. Apathy and executive dysfunction are exacerbated during AEH, particularly in association with lower CD4 counts. PMID- 27008245 TI - Reproducibility of tDCS Results in a Randomized Trial: Failure to Replicate Findings of tDCS-Induced Enhancement of Verbal Fluency. AB - BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to enhance verbal productivity, but the finding and extent of enhancement vary across studies. Few attempts to replicate positive tDCS findings have been reported, suggesting the possibility of publication bias. OBJECTIVE: We aimed to replicate the tDCS methodology and findings of Cattaneo, Pisoni, and Papagno (2011, Neuroscience 183:64-70) in a new population sample. We hypothesized that our study of anodal tDCS would improve verbal fluency production similarly to the original study. METHODS: In our single-blind, sham-controlled crossover experiment, 14 healthy young adults were randomly assigned to receive 2 mA of anodal and sham stimulation to the Broca area in counterbalanced order before completing verbal fluency tasks. RESULTS: Participants tolerated the stimulation well. Despite closely mirroring the original study methods, we saw no main effect of stimulation condition: F1,13=0.002, P=0.97, letter fluency sham mean (standard deviation)=16.8 (2.3), letter fluency anodal=17.5 (3.8), category fluency sham=25.3 (5.4), or category fluency anodal=24.7 (5.2), eta<=0.01. CONCLUSIONS: While tDCS may enhance cerebral functions in general, the lack of consistency between studies suggests either that this tDCS protocol does not affect verbal fluency or, at minimum, that tDCS may be more sensitive to experimental conditions than has been thought. Our findings also highlight the need for replication studies in brain stimulation research. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT01602263). PMID- 27008246 TI - Allocentric But Not Egocentric Pseudoneglect of Peripersonal Space. AB - BACKGROUND AND OBJECTIVE: Healthy adults often deviate leftward on line bisection tasks (allocentric pseudoneglect) but rightward on body part bisection tasks (egocentric pseudoneglect). People visually estimate distance in peripersonal space by comparing the distance to the length of a body part such as an arm's length (an egocentric reference) or using standard units of distance such as inches (an allocentric reference). Our objective was to learn whether people have pseudoneglect when estimating distances in peripersonal space using egocentric versus allocentric reference frames. METHODS: Twelve healthy participants standing either next to or 5 feet away from a wall were asked to move away from or toward the wall such that their shoulder would be what they judged to be an arm's length or a distance of 1, 2, or 3 feet from the wall. RESULTS: The participants estimated their arm's length more accurately than the standard units of distance (possibly related to learning and practice). Participants were more precise when estimating the length of their left than their right arm. When estimating standard units of distance, participants underestimated the distances on their left side more than on their right. CONCLUSIONS: Our results support the postulate that left pseudoneglect is an allocentric phenomenon related to a hemispheric asymmetry in computing allocentric distances. The participants underestimated 2 and 3 feet, but overestimated 1 foot. This dichotomy may relate to using focused versus distributed attention. The brain mechanisms leading to these asymmetries remain to be determined. PMID- 27008247 TI - Elevated Brain-Derived Neurotrophic Factor Correlates Negatively with Severity and Duration of Major Depressive Episodes. AB - BACKGROUND AND OBJECTIVE: Major depressive disorder is a neuropsychiatric condition associated with neurochemical changes that alter levels of neurotrophins. We aimed to measure serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in patients experiencing their first episode of major depression and to examine those levels in relation to the severity and duration of the depressive episode. METHODS: We recruited 85 participants: 44 drug-free patients with major depression (35 women, 9 men) and 41 healthy controls (32 women, 9 men). We used the Hamilton Rating Scale for Depression to assess the severity of the patients' depression. We assessed the controls' mental health according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed, criteria. To assess all participants' stress levels, we used the Holmes and Rahe stress scale. We measured all participants' serum BDNF and NGF levels via enzyme-linked immunosorbent assay. RESULTS: The mean stress score was significantly higher in the patients than the controls (P=0.03). The patients had higher serum BDNF than the controls (P=0.001), but similar NGF levels. BDNF levels correlated negatively with symptom severity (r=-0.33, P=0.03) and duration (r=-0.2, P=0.06). NGF levels did not correlate with stress or with severity or duration of depressive episode. CONCLUSIONS: These findings suggest that an elevated serum BDNF level may contribute to the pathophysiology of major depressive disorder. The findings also indicate a possible role for BDNF in altering the clinical course of the condition. PMID- 27008248 TI - Semantic Feature Training for the Treatment of Anomia in Alzheimer Disease: A Preliminary Investigation. AB - OBJECTIVE: This is a preliminary investigation into the effectiveness of semantic feature training for the treatment of anomia in Alzheimer disease (AD). BACKGROUND: Anomia is a common clinical characteristic of AD. It is widely held that anomia in AD is caused by the combination of cognitive deficits and progressive loss of semantic feature information. Therapy that aims to help participants relearn or retain semantic features should, therefore, help treat anomia in AD. METHODS: Two men with AD and one man with progressive nonfluent aphasia received 10 treatment sessions focused on relearning the names of 20 animals and 20 fruits. Within each category, half of the items were of high and half were of low typicality. We individualized treatment items to each participant, using items that each had not named correctly at baseline. Treatment sessions consisted of naming, category sorting, and semantic feature verification tasks. RESULTS: Both participants with AD showed post-treatment improvements in naming, and one maintained the treatment effects at 6-week follow-up. The semantic category of the treatment items influenced post-treatment outcomes, but typicality did not. In contrast to the participants with AD, the man with progressive nonfluent aphasia had no improvement in naming ability. CONCLUSIONS: Our results suggest the potential viability of semantic feature training to treat anomia in AD and, therefore, the need for further research. PMID- 27008249 TI - Relationship Between Closing-In and Spatial Neglect: A Case Study. AB - We describe a right-brain-damaged patient with extrapersonal neglect, dysexecutive deficits, and closing-in. Because no study has investigated the relationship between spatial neglect and closing-in in patients with focal brain damage, we assessed how spatial factors (drawing direction: left-to-right, right to-left, radial) and attentional load (single versus dual task copying; the concurrent task was counting aloud) interacted in determining our patient's closing-in. We found that her closing-in was worst when she copied the stimulus (Luria's line) from left to right; greater attentional load significantly worsened her closing-in in the right-to-left direction. Closing-in seems to be caused by a pathologic release of motor behavior, analogous to other productive manifestations of extrapersonal neglect. PMID- 27008250 TI - Silk route to the acceptance and re-implementation of bacteriophage therapy. AB - This multidisciplinary expert panel opinion on bacteriophage therapy has been written in the context of a society that is confronted with an ever-increasing number of antibiotic resistant bacteria. To avoid the return to a pre-antibiotic era, alternative treatments are urgently needed. The authors aim to contribute to the opinion formation of relevant stakeholders on how to potentially develop an infrastructure and legislation that paves the way for the acceptance and re implementation of bacteriophage therapy. PMID- 27008251 TI - From the bench to the market: the long, sinuous and rocky road. PMID- 27008253 TI - The presence of Helicobacter pylori in oral cavities of patients with leukoplakia and oral lichen planus. AB - OBJECTIVE: Helicobacter pylori infection is one of the most common bacterial infections in men. This gastrointestinal pathogen is closely related to gastritis, peptic ulcers, and the increased risk of gastric cancer. Numerous studies have indicated oral cavities as possible Helicobacter pylori reservoirs. Helicobacter pylori has been detected both in supragingival and subgingival plaques, and also in saliva. In addition, the relationship between lesions of oral mucosa and the presence of H. pylori has been evaluated and described in some studies. The aim of this study was to assess the presence of Helicobacter pylori DNA in the oral cavity of patients with oral leukoplakia and oral lichen planus. MATERIAL AND METHODS: The study included 54 patients with oral leukoplakia, 72 with oral lichen planus lesions, and 40 healthy controls. The presence of Helicobacter pylori in oral cavity samples was analyzed using a single-step Polymerase Chain Reaction (PCR) method. All patients underwent a periodontal examination and the following clinical parameters were collected: pocket depth, bleeding, and plaque indexes. The periodontal status was assessed using the Offenbacher classification. RESULTS: In most patients, pathological lesions were in typical sites on the buccal mucosa (leukoplakia in 88%, and oral lichen planus in 93% of patients). The DNA of the Helicobacter pylori was present in 20% of patients with leukoplakia and 23% of patients with lichen planus. We did not find the DNA of H. pylori in healthy controls. The periodontal status described by periodontal indices was worse in the investigated group than in the control group. CONCLUSION: These findings suggest that the H. pylori presence in oral cavities may be related with leukoplakia and lichen planus oral lesions. PMID- 27008252 TI - Long-term effects of vertical bone augmentation: a systematic review. AB - Extraction, periodontitis, or trauma can cause a reduction on the alveolar ridge. This could result in an insufficient alveolar bone width and height. Different techniques of vertical bone augmentation are described in literature. However, nowadays there is not enough evidence against lateral augmentation procedures to verify if these techniques are stable over a long period of time. OBJECTIVE: This review analyses the different techniques that are used to vertically augment the bone and evaluate if these techniques are stable over a long period of time. MATERIAL AND METHODS: The MEDLINE-PubMed database was searched from its earliest records until December 22, 2014. The following search term was used: Alveolar Ridge augmentation [MESH]. Several journals were hand searched and some authors were contacted for additional information. The primary outcome measure that was analyzed was marginal bone level change around dental implants in the augmented sites, and the secondary outcomes were survival and success rates of dental implants placed in the augmented sites. RESULTS: The search yielded 203 abstracts. Ultimately, 90 articles were selected, describing 51 studies meeting the eligibility criteria. The marginal bone level change for the inlay technique and vertical guided bone regeneration are in agreement with the success criteria. Alveolar distraction showed more marginal bone level change after the first year of loading, and for the inlay technique very few studies were available. CONCLUSIONS: Based on the available data in the current existing studies with a follow-up period of at least 4 to 5 years, one can summarize that there seems to be a trend that the onlay technique, alveolar distraction, and vertical guided bone regeneration are stable for at least 4 to 5 years. PMID- 27008255 TI - In vitro re-hardening of artificial enamel caries lesions using enamel matrix proteins or self-assembling peptides. AB - OBJECTIVES: To assess the re-hardening potential of enamel matrix derivatives (EMD) and self-assembling peptides in vitro, hypothesizing that these materials may increase the mineralization of artificial carious lesions and improve hardness profiles. MATERIAL AND METHODS: Forty-eight enamel samples were prepared from extracted bovine lower central incisors. After embedding and polishing, nail varnish was applied, leaving a defined test area. One third of this area was covered with a flowable composite (non-demineralized control). The remaining area was demineralized in an acidic buffer solution for 18 d to simulate a carious lesion. Half the demineralized area was then covered with composite (demineralized control), while the last third was left open for three test and one control treatments: (A) Application of enamel-matrix proteins (EMD - lyophilized protein fractions dissolved in acetic acid, Straumann), (B) self assembling peptides (SAP, Curodont), or (C) amine fluoride solution (Am-F, GABA) for 5 min each. Untreated samples (D) served as control. After treatment, samples were immersed in artificial saliva for four weeks (remineralization phase) and microhardness (Knoop) depth profiles (25-300 um) were obtained at sections. Two way ANOVA was calculated to determine differences between the areas (re-hardening or softening). RESULTS: Decalcification resulted in significant softening of the subsurface enamel in all groups (A-D). A significant re-hardening up to 125 um was observed in the EMD and SAP groups. CONCLUSIONS: This study showed that EMD and SAP were able to improve the hardness profiles when applied to deep demineralized artificial lesions. However, further research is needed to verify and improve this observed effect. PMID- 27008254 TI - Influence of pH, bleaching agents, and acid etching on surface wear of bovine enamel. AB - Development of new materials for tooth bleaching justifies the need for studies to evaluate the changes in the enamel surface caused by different bleaching protocols. OBJECTIVE: The aim of this study was to evaluate the bovine dental enamel wear in function of different bleaching gel protocols, acid etching and pH variation. MATERIAL AND METHODS: Sixty fragments of bovine teeth were cut, obtaining a control and test areas. In the test area, one half received etching followed by a bleaching gel application, and the other half, only the bleaching gel. The fragments were randomly divided into six groups (n=10), each one received one bleaching session with five hydrogen peroxide gel applications of 8 min, activated with hybrid light, diode laser/blue LED (HL) or diode laser/violet LED (VHL) (experimental): Control (C); 35% Total Blanc Office (TBO35HL); 35% Lase Peroxide Sensy (LPS35HL); 25% Lase Peroxide Sensy II (LPS25HL); 15% Lase Peroxide Lite (LPL15HL); and 10% hydrogen peroxide (experimental) (EXP10VHL). pH values were determined by a pHmeter at the initial and final time periods. Specimens were stored, subjected to simulated brushing cycles, and the superficial wear was determined (MUm). ANOVA and Tukey's tests were applied (alpha=0.05). RESULTS: The pH showed a slight decrease, except for Group LPL15HL. Group LPS25HL showed the highest degree of wear, with and without etching. CONCLUSION: There was a decrease from the initial to the final pH. Different bleaching gels were able to increase the surface wear values after simulated brushing. Acid etching before bleaching increased surface wear values in all groups. PMID- 27008257 TI - Corrosion behavior of zirconia in acidulated phosphate fluoride. AB - OBJECTIVE: The corrosion behavior of zirconia in acidulated phosphate fluoride (APF) representing acidic environments and fluoride treatments was studied. MATERIAL AND METHODS: Zirconia rods were immersed in 1.23% and 0.123% APF solutions and maintained at 37 degrees C for determined periods of time. Surfaces of all specimens were imaged using digital microscopy and scanning electron microscopy (SEM). Sample mass and dimensions were measured for mass loss determination. Samples were characterized by powder X-ray diffraction (XRD) to detect changes in crystallinity. A biosensor based on electrochemical impedance spectroscopy (EIS) was used to detect ion dissolution of material into the immersion media. RESULTS: Digital microscopy revealed diminishing luster of the materials and SEM showed increased superficial corrosion of zirconia submerged in 1.23% APF. Although no structural change was found, the absorption of salts (sodium phosphate) onto the surface of the materials bathed in 0.123% APF was significant. EIS indicated a greater change of impedance for the immersion solutions with increasing bathing time. CONCLUSION: Immersion of zirconia in APF solutions showed deterioration limited to the surface, not extending to the bulk of the material. Inferences on zirconia performance in acidic oral environment can be elucidated from the study. PMID- 27008256 TI - Impact of micronutrients supplementation on bone repair around implants: microCT and counter-torque analysis in rats. AB - The use of natural substances and micronutritional approaches has been suggested as a therapeutic alternative to benefit the bone healing associated with no side effects. Nevertheless, the influence of micronutritional interventions with therapeutic proprieties on the bone repair has yet to be intensely evaluated, and no evidence is available exploring the impact of micronutrient supplementation on the peri-implant bone healing. OBJECTIVE: This study investigated the effect of micronutrients supplementation on the bone repair around implants. MATERIAL AND METHODS: One screw-shaped titanium implant was inserted in each tibia of each rat, which were assigned to: daily administration, for 30 d, of the placebo solution (Placebo group-n:18) or micronutrients supplementation (Micronutrients group-n:18), based on calcium, magnesium, zinc, and vitamin D3 intake. After, the animals were sacrificed. One of the implants was removed by applying a counter torque force to evaluate the force to rupture the bone-implant interface. The other implant was evaluated by microcomputed tomography (CT) examination to determine the bone-to-implant contact (BIC) and the bone volume (BV/TV). RESULTS: No statistically significant differences were observed between the groups for both counter-torque values and microCT parameters (p>0.05). CONCLUSION: Within the limits of this study, micronutrients supplementation did not provide additional benefits to the bone healing around dental implants. PMID- 27008258 TI - Preventive effect of toothpastes with MMP inhibitors on human dentine erosion and abrasion in vitro. AB - The use of gels and mouthrinses with MMP inhibitors (chlorhexidine, and green tea extract) was shown to prevent erosive wear. The aim of this study was to analyze the protective effect of toothpastes containing MMP inhibitors on dentine loss induced by erosion in vitro. MATERIAL AND METHODS: Five groups each containing 12 specimens of human root dentine were prepared. The specimens were subjected to 1 min erosion by immersion in a cola drink, 4 times a day, for 5 d. Each day, after the first and last erosive challenges, the specimens were brushed for 15 s with a slurry of dentifrice and water (1:3) containing placebo, 1,100 ppm fluoride, 0.61% green tea extract, 0.12% chlorhexidine or 0.004% chlorhexidine (commercial toothpaste). Between the acid challenges, the specimens were stored in artificial saliva with remineralizing potential until the next treatment. Dentine loss was determined using profilometry. Data were analyzed using one-way ANOVA after log transform (p<0.05). RESULTS: The mean wear values (MUm) were as follows: placebo 1.83+/-0.53; 0.61% green tea extract 1.00+/-0.21; fluoride 1.27+/-0.43; 0.12% chlorhexidine 1.19+/-0.30; and 0.004% chlorhexidine 1.22+/-0.46. There was a significant difference in wear between placebo and all the treatment toothpastes, which did not differ from each other. CONCLUSION: The results suggest that toothpastes containing MMP inhibitors are as effective as those based on NaF in preventing dentine erosion and abrasion. PMID- 27008259 TI - Lactobacillus rhamnosus could inhibit Porphyromonas gingivalis derived CXCL8 attenuation. AB - An increasing body of evidence suggests that the use of probiotic bacteria is a promising intervention approach for the treatment of inflammatory diseases with a polymicrobial etiology. P. gingivalis has been noted to have a different way of interacting with the innate immune response of the host compared to other pathogenic bacteria, which is a recognized feature that inhibits CXCL8 expression. OBJECTIVE: The aim of the study was to determine if P. gingivalis infection modulates the inflammatory response of gingival stromal stem cells (G MSSCs), including the release of CXCL8, and the expression of TLRs and if immunomodulatory L. rhamnosus ATCC9595 could prevent CXCL8 inhibition in experimental inflammation. MATERIAL AND METHODS: G-MSSCs were pretreated with L. rhamnosus ATCC9595 and then stimulated with P. gingivalis ATCC33277. CXCL8 and IL 10 levels were investigated with ELISA and the TLR-4 and 2 were determined through flow cytometer analysis. RESULTS: CXCL8 was suppressed by P. gingivalis and L. rhamnosus ATCC9595, whereas incubation with both strains did not abolish CXCL8. L. rhamnosus ATCC9595 scaled down the expression of TLR4 and induced TLR2 expression when exposed to P. gingivalis stimulation (p<0.01). CONCLUSIONS: These findings provide evidence that L. rhamnosus ATCC9595 can modulate the inflammatory signals and could introduce P. gingivalis to immune systems by inducing CXCL8 secretion. PMID- 27008260 TI - Effects of epicatechin, a crosslinking agent, on human dental pulp cells cultured in collagen scaffolds. AB - OBJECTIVE: The purpose of this study was to investigate the biological effects of epicatechin (ECN), a crosslinking agent, on human dental pulp cells (hDPCs) cultured in collagen scaffolds. MATERIAL AND METHOD: To evaluate the effects of ECN on the proliferation of hDPCs, cell counting was performed using optical and fluorescent microscopy. Measurements of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time polymerase chain reactions were performed to assess odontogenic differentiation. The compressive strength and setting time of collagen scaffolds containing ECN were measured. Differential scanning calorimetry was performed to analyze the thermal behavior of collagen in the presence of ECN. RESULTS: Epicatechin increased ALP activity, mineralized nodule formation, and the mRNA expression of dentin sialophosphoprotein (DSPP), a specific odontogenic-related marker. Furthermore, ECN upregulated the expression of DSPP in hDPCs cultured in collagen scaffolds. Epicatechin activated the extracellular signal-regulated kinase (ERK) and the treatment with an ERK inhibitor (U0126) blocked the expression of DSPP. The compressive strength was increased and the setting time was shortened in a dose-dependent manner. The number of cells cultured in the ECN-treated collagen scaffolds was significantly increased compared to the cells in the untreated control group. CONCLUSIONS: Our results revealed that ECN promoted the proliferation and differentiation of hDPCs. Furthermore, the differentiation was regulated by the ERK signaling pathway. Changes in mechanical properties are related to cell fate, including proliferation and differentiation. Therefore, our study suggests the ECN treatment might be desirable for dentin-pulp complex regeneration. PMID- 27008261 TI - Accuracy of intraoral and extraoral digital data acquisition for dental restorations. AB - The computer-aided design (CAD) and computer-aided manufacturing (CAM) process chain for dental restorations starts with taking an impression of the clinical situation. For this purpose, either extraoral digitization of gypsum models or intraoral digitization can be used. Despite the increasing use of dental digitizing systems, there are only few studies on their accuracy. OBJECTIVE: This study compared the accuracy of various intraoral and extraoral digitizing systems for dental CAD/CAM technology. MATERIAL AND METHODS: An experimental setup for three-dimensional analysis based on 2 prepared ceramic master dies and their corresponding virtual CAD-models was used to assess the accuracy of 10 extraoral and 4 intraoral optical non-contact dental digitizing systems. Depending on the clinical procedure, 10 optical measurements of either 10 duplicate gypsum dies (extraoral digitizing) or directly of the ceramic master dies (intraoral digitizing) were made and compared with the corresponding CAD-models. RESULTS: The digitizing systems showed differences in accuracy. However, all topical systems were well within the benchmark of +/-20 um. These results apply to single tooth measurements. CONCLUSIONS: Study results are limited, since only single teeth were used for comparison. The different preparations represent various angles and steep and parallel opposing tooth surfaces (incisors). For most digitizing systems, the latter are generally the most difficult to capture. Using CAD/CAM technologies, the preparation angles should not be too steep to reduce digitizing errors. Older systems might be limited to a certain height or taper of the prepared tooth, whereas newer systems (extraoral as well as intraoral digitization) do not have these limitations. PMID- 27008262 TI - Evaluation of an experimental rat model for comparative studies of bleaching agents. AB - Dental materials, in general, are tested in different animal models prior to their clinical use in humans, except for bleaching agents. OBJECTIVES: To evaluate an experimental rat model for comparative studies of bleaching agents by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats' vital teeth. MATERIAL AND METHODS: The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals (control) were untreated. The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated by histomorphometric analysis with inflammatory cell counting in the coronal and radicular thirds of the pulp. The counting of fibroblasts was also performed. Scores were attributed to the odontoblastic layer and to vascular changes. The tertiary dentin area and the pulp chamber central area were histomorphometrically measured. Data were compared by the analysis of variance and the Kruskal-Wallis test (p<0.05). RESULTS: After 2 days, the amount of inflammatory cells increased in the occlusal third of the coronal pulp until the time of 15 min for both concentrations of bleaching gels. In 30 and 45 min groups of each concentration, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, a reduction in the pulp chamber central area and an enlargement of tertiary dentin area were observed without the detection of inflammation areas. CONCLUSION: The rat model of extra coronal bleaching showed to be adequate for bleaching protocols studies, as it was possible to observe alterations in the pulp tissues and in the tooth structure caused by different concentrations and periods of application of bleaching agents. PMID- 27008263 TI - Retraction. PMID- 27008264 TI - Erratum. PMID- 27008265 TI - Erratum to: individual-level changes in self-rated health before and during the economic crisis in Europe. PMID- 27008266 TI - A detailed study of the volatile components of Plectranthus asirensis of Saudi Arabian origin. AB - Essential oil composition of Plectranthus asirensis grown in Saudi Arabia was chemically analysed for the first time by various gas chromatography techniques (GC-MS, GC-FID, Co-GC, LRI determination and database and literature searches) using two different stationary phase columns (polar and nonpolar). This analysis led to the characterisation of a total of 124 components representing 98.5% of the total oil composition. The results revealed that P. asirensis oil was mainly dominated by monoterpenoids (90.7%) in which most representative constituents were thymol (66.0 +/- 0.36%), gamma-terpinene (14.0 +/- 0.18%), p-cymene (5.2 +/- 0.06%) and beta-caryophyllene (3.0 +/- 0.03%). It is worth mentioning here that this is the first report on the phytochemical constituents of P. asirensis. PMID- 27008268 TI - Discriminant Incoherent Component Analysis. AB - Face images convey rich information which can be perceived as a superposition of low-complexity components associated with attributes, such as facial identity, expressions, and activation of facial action units (AUs). For instance, low-rank components characterizing neutral facial images are associated with identity, while sparse components capturing non-rigid deformations occurring in certain face regions reveal expressions and AU activations. In this paper, the discriminant incoherent component analysis (DICA) is proposed in order to extract low-complexity components, corresponding to facial attributes, which are mutually incoherent among different classes (e.g., identity, expression, and AU activation) from training data, even in the presence of gross sparse errors. To this end, a suitable optimization problem, involving the minimization of nuclear and l1 -norm, is solved. Having found an ensemble of class-specific incoherent components by the DICA, an unseen (test) image is expressed as a group-sparse linear combination of these components, where the non-zero coefficients reveal the class(es) of the respective facial attribute(s) that it belongs to. The performance of the DICA is experimentally assessed on both synthetic and real world data. Emphasis is placed on face analysis tasks, namely, joint face and expression recognition, face recognition under varying percentages of training data corruption, subject-independent expression recognition, and AU detection by conducting experiments on four data sets. The proposed method outperforms all the methods that are compared with all the tasks and experimental settings. PMID- 27008267 TI - A Highly Efficient and Simple Construction Strategy for Producing Recombinant Baculovirus Bombyx mori Nucleopolyhedrovirus. AB - The silkworm baculovirus expression system is widely used to produce recombinant proteins. Several strategies for constructing recombinant viruses that contain foreign genes have been reported. Here, we developed a novel defective-rescue BmNPV Bacmid (reBmBac) expression system. A CopyControl origin of replication was introduced into the viral genome to facilitate its genetic manipulation in Escherichia coli and to ensure the preparation of large amounts of high quality reBmBac DNA as well as high quality recombinant baculoviruses. The ORF1629, cathepsin and chitinase genes were partially deleted or rendered defective to improve the efficiency of recombinant baculovirus generation and the expression of foreign genes. The system was validated by the successful expression of luciferase reporter gene and porcine interferon gamma. This system can be used to produce batches of recombinant baculoviruses and target proteins rapidly and efficiently in silkworms. PMID- 27008269 TI - Targeting GLI1 Suppresses Cell Growth and Enhances Chemosensitivity in CD34+ Enriched Acute Myeloid Leukemia Progenitor Cells. AB - BACKGROUND/AIMS: Resistance of leukemia stem cells (LSCs) to chemotherapy in patients with acute myeloid leukemia (AML) causes relapse of disease. Hedgehog (Hh) signaling plays a critical role in the maintenance and differentiation of cancer stem cells. Yet its role in AML remains controversial. The purpose of the present study is to investigate the role of GLI1, the transcriptional activator of Hh signaling, in AML progenitor cells and to explore the anti-AML effects of GLI small-molecule inhibitor GANT61. METHODS: The expression of GLI1 mRNA and protein were examined in AML progenitor cells and normal cells. The proliferation, colony formation, apoptosis and differentiation of AML progenitor cells were also analyzed in the presence of GANT61. RESULTS: Kasumi-1 and KG1a cells, containing more CD34+ cells, expressed higher level of GLI1 compared to U937 and NB4 cells with fewer CD34+ cells. Consistently, a positive correlation between the protein levels of GLI1 and CD34 was validated in the bone marrow mononuclear cells (BMMC) of AML patients tested. GANT61 inhibited the proliferation and colony formation in AML cell lines. Importantly, GANT61 induced apoptosis in CD34+ enriched Kasumi-1 and KG1a cells, whereas it induced differentiation in U937 and NB4 cells. Furthermore, GANT61 enhanced the cytotoxicity of cytarabine (Ara-c) in primary CD34+ AML cells, indicating that inhibition of GLI1 could be a promising strategy to enhance chemosensitivity. CONCLUSIONS: The present findings suggested that Hh signaling was activated in AML progenitor cells. GLI1 acted as a potential target for AML therapy. PMID- 27008270 TI - Dietary Advanced Glycation End Products and Their Potential Role in Cardiometabolic Disease in Children. AB - The rising incidence of obesity and metabolic diseases such as diabetes mellitus and cardiovascular disease in adolescents and young adults is of grave concern. Recent studies favor a role of lifestyle factors over genetics in the perpetuation of inflammation, insulin resistance and oxidative stress, which are pathophysiologic processes common to the above diseases; furthermore, the importance of dietary factors in addition to calories and physical activity in these processes is being increasingly recognized. Advanced glycation end products (AGEs) belong to a category of dietary oxidants which have been implicated in the pathogenesis of inflammation, oxidative stress, insulin resistance, beta-cell failure and endothelial dysfunction. This paper reviews the studies of AGEs with a focus on their role in cardiometabolic disease in children. A Medline search was performed using the key words 'childhood obesity', 'metabolic syndrome' and 'advanced glycation end products'. Articles published in English between 1975 and 2015 and their references were reviewed. While most studies were performed in adults, a few studies also demonstrated a role of AGEs in obesity and associated cardiometabolic comorbidities in the younger population. Available evidence suggests an involvement of AGEs in the pathogenesis of adiposity and beta-cell failure in children. Potential areas for further research to investigate underlying mechanisms are proposed. PMID- 27008271 TI - Inheritance of Chiari-Like Malformation: Can a Mixed Breeding Reduce the Risk of Syringomyelia? AB - Canine Chiari-like malformation (CM) is a complex abnormality of the skull and craniocervical junction associated with miniaturization and brachycephaly which can result in the spinal cord disease syringomyelia (SM). This study investigated the inheritance of CM in a Griffon Bruxellois (GB) family and feasibility of crossbreeding a brachycephalic CM affected GB with a mesaticephalic normal Australian terrier and then backcrossing to produce individuals free of the malformation and regain GB breed characteristics. The study family cohort (n = 27) included five founder dogs from a previous baseline study of 155 GB which defined CM as a global malformation of the cranium and craniocervical junction with a shortened skull base and increased proximity of the cervical vertebrae to the skull. T1-weighted sagittal DICOM images of the brain and craniocervical junction were analysed for five significant traits (two angles, three lines) identified from the previous study and subsequent Qualitative Trait Loci analysis. Mean measurements for mixed breed, pure-breed and baseline study groups were compared. Results indicated that mixed breed traits posed less risk for CM and SM and were useful to distinguish the phenotype. Moreover on the MR images, the filial relationships displayed by the traits exhibited segregation and those presenting the greatest risk for CM appeared additive towards the severity of the condition. The external phenotypes revealed that by outcrossing breed types and with careful selection of appropriate conformation characteristics in the first generation, it is possible to regain the GB breed standard and reduce the degree of CM. The four GB affected with SM in the study all exhibited reduced caudal skull development compared to their relatives. The craniocervical traits may be useful for quantifying CM and assessing the possibility of SM thus assisting breeders with mate selection. However, such a system requires validation to ensure appropriateness for all breeds at risk. PMID- 27008273 TI - A genetics-based description of Symbiodinium minutum sp. nov. and S. psygmophilum sp. nov. (Dinophyceae), two dinoflagellates symbiotic with cnidaria. AB - Traditional approaches for describing species of morphologically cryptic and often unculturable forms of endosymbiotic dinoflagellates are problematic. Two new species in the genus Symbiodinium Freudenthal 1962 are described using an integrative evolutionary genetics approach: Symbiodinium minutum sp. nov. are harbored by widespread tropical anemones in the genus Aiptasia; and Symbiodinium psygmophilum sp. nov. are harbored by subtropical and temperate stony corals (e.g., Astrangia, Cladocora, and Oculina) from the Atlantic Ocean and Mediterranean Sea. Both new species are readily distinguished from each other by phylogenetic disparity and reciprocal monophyly of several nucleic acid sequences including nuclear ribosomal internal transcribed spacers 1 and 2, single copy microsatellite flanker Sym15, mitochondrial cytochrome b, and the chloroplast 23S rRNA gene. Such molecular evidence, combined with well-defined differences in cell size, physiology (thermal tolerance), and ecology (host compatibility) establishes these organisms as distinct species. Future descriptions of Symbiodinium spp. will need to emphasize genetics-based descriptions because significant morphological overlap in this group obscures large differences in ecology and evolutionary divergence. By using molecular evidence based on conserved and rapidly evolving genes analyzed from a variety of samples, species boundaries are defined under the precepts of Evolutionary and Biological Species Concepts without reliance on an arbitrary genetic distance metric. Because ecological specialization arises through genetic adaptations, the Ecological Species Concept can also serve to delimit many host-specific Symbiodinium spp. PMID- 27008272 TI - Homocysteinemia is Associated with a Lower Degree of PBMC LINE-1 Methylation and a Higher Risk of CIN 2C in the U.S. Post-Folic Acid Fortification Era. AB - The primary aim of the study was to determine whether plasma concentrations of homocysteine (Hcy), a functional indicator of methyl donor nutrients, are associated with altered risk of higher grades of cervical intraepithelial neoplasia (CIN 2+) and the degree of methylation in long interspersed nucleotide elements (LINE-1s) of peripheral blood mononuclear cells, a potential biomarker of CIN 2+ in a population of women exposed to the United States folic acid fortification program. The secondary aim was to assess the determinants of plasma Hcy in the same population. The study included 457 women diagnosed with either CIN 2+ (cases, n = 132) or <= CIN 1 (non-cases, n = 325). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors of cervical cancer. Women with higher Hcy concentrations were at a greater risk of being diagnosed with CIN 2+ [odds ratio (OR) = 1.86, P = 0.005]. Higher plasma folate concentrations were a significant determinant of lower Hcy (OR = 0.40, P = 0.0002). Women with higher Hcy concentrations were more likely to have a lower degree of LINE-1 methylation (OR = 2.30, P = 0.0007). These results suggested that further improvement in folate status in this population may be beneficial for lowering Hcy and improving the degree of LINE-1 methylation. PMID- 27008274 TI - The Switch from Low-Pressure Sodium to Light Emitting Diodes Does Not Affect Bat Activity at Street Lights. AB - We used a before-after-control-impact paired design to examine the effects of a switch from low-pressure sodium (LPS) to light emitting diode (LED) street lights on bat activity at twelve sites across southern England. LED lights produce broad spectrum 'white' light compared to LPS street lights that emit narrow spectrum, orange light. These spectral differences could influence the abundance of insects at street lights and thereby the activity of the bats that prey on them. Most of the bats flying around the LPS lights were aerial-hawking species, and the species composition of bats remained the same after the switch-over to LED. We found that the switch-over from LPS to LED street lights did not affect the activity (number of bat passes), or the proportion of passes containing feeding buzzes, of those bat species typically found in close proximity to street lights in suburban environments in Britain. This is encouraging from a conservation perspective as many existing street lights are being, or have been, switched to LED before the ecological consequences have been assessed. However, lighting of all spectra studied to date generally has a negative impact on several slow flying bat species, and LED lights are rarely frequented by these 'light intolerant' bat species. PMID- 27008275 TI - Quality of Life of Adult Patients With Attention-Deficit/Hyperactivity Disorder Taking Methylphenidate. PMID- 27008276 TI - The Role of Psychology in Pediatric Palliative Care. AB - Pediatric medicine increasingly has recognized the value of integrating behavioral health in medical care, but this trend has not yet extended to pediatric palliative care. Results from a recent survey of pediatric palliative care programs across the United States indicate that team composition almost never included a psychologist. This article presents a model of collaborative care to optimize the integration of psychosocial and medical aspects of treatment in pediatric palliative care, delineating how a psychologist adds to this model. This article argues that psychology brings specialized skills in assessment, intervention, and research that fit with the premise of palliative care as a holistic approach that relieves symptoms. Systematic inclusion of psychologists on pediatric palliative care teams may help to improve effectiveness of services as well as extend the knowledge base of mental health in pediatric palliative care. PMID- 27008277 TI - Hydrological Classification, a Practical Tool for Mangrove Restoration. AB - Mangrove restoration projects, aimed at restoring important values of mangrove forests after degradation, often fail because hydrological conditions are disregarded. We present a simple, but robust methodology to determine hydrological suitability for mangrove species, which can guide restoration practice. In 15 natural and 8 disturbed sites (i.e. disused shrimp ponds) in three case study regions in south-east Asia, water levels were measured and vegetation species composition was determined. Using an existing hydrological classification for mangroves, sites were classified into hydrological classes, based on duration of inundation, and vegetation classes, based on occurrence of mangrove species. For the natural sites hydrological and vegetation classes were similar, showing clear distribution of mangrove species from wet to dry sites. Application of the classification to disturbed sites showed that in some locations hydrological conditions had been restored enough for mangrove vegetation to establish, in some locations hydrological conditions were suitable for various mangrove species but vegetation had not established naturally, and in some locations hydrological conditions were too wet for any mangrove species (natural or planted) to grow. We quantified the effect that removal of obstructions such as dams would have on the hydrology and found that failure of planting at one site could have been prevented. The hydrological classification needs relatively little data, i.e. water levels for a period of only one lunar tidal cycle without additional measurements, and uncertainties in the measurements and analysis are relatively small. For the study locations, the application of the hydrological classification gave important information about how to restore the hydrology to suitable conditions to improve natural regeneration or to plant mangrove species, which could not have been obtained by estimating elevation only. Based on this research a number of recommendations are given to improve the effectiveness of mangrove restoration projects. PMID- 27008278 TI - Aureolysin of Staphylococcus warneri M accelerates its proteolytic cascade, and participates in biofilm formation. AB - The aureolysin (Aur) gene of S. warneri M (aurWM) was cloned and sequenced. Analyses of the aurWM-inactivated mutant (S. warneri Mau) suggested that AurWM was probably associated with efficient processing of the PROM protease (homolog of V8/SspA serine protease), whereas considerable amount of mature-PROC protease (homolog of SspB cysteine protease) accumulated without AurWM. Additionally, AurWM appeared to affect biofilm formation in an uncertain suppressive way. PMID- 27008279 TI - Pyrosequencing Using SL and 5S rRNA as Molecular Markers for Identifying Zoonotic Filarial Nematodes in Blood Samples and Mosquitoes. AB - BACKGROUNDS: Lymphatic filariasis is principally caused by Wuchereria bancrofti, and Brugia malayi. The other two filarial nematode species, Brugia pahangi and Dirofilaria immitis, possibly cause human zoonotic diseases. METHODS: We propose the development of a PCR assay linked with DNA pyrosequencing as a rapid tool to identify W. bancrofti, B. malayi, B. pahangi, and D. immitis in blood samples and mosquitoes. Primers targeting the fragment of the 5S ribosomal RNA and spliced leader sequences were newly designed and developed to identify these four filarial nematodes. Analytical sensitivity and specificity were evaluated. RESULTS: Pyrosequencing determination of nucleotide variations within 36 nucleotides for B. malayi and B. pahangi, and 32 nucleotides for W. bancrofti and D. immitis is sufficient for differentiation of those filarial nematodes, and for detection of intraspecies genetic variation of B. malayi. This analysis could detect a single B. malayi, B. pahangi, W. bancrofti, and D. immitis microfilaria in blood samples. CONCLUSIONS: Overall, the PCR-linked pyrosequencing-based method was faster than direct sequencing and less expensive than real-time PCR or direct sequencing. This is the possibility of choice that can be applied in a high-throughput platform for identification and surveillance of reservoirs and vectors infected with lymphatic filaria in endemic areas. PMID- 27008280 TI - The evaluation of eustachian tube paratubal structures using magnetic resonance imaging in patients with chronic suppurative otitis media. AB - Conclusion Eustachian tube (ET) dysfunction, which plays a role in the pathogenesis chronic suppurative otitis media (CSOM), does not seem to be due to differences in paratubal structures. Objective The aim of this study was to compare the magnetic resonance imaging (MRI) findings of the paratubal structures of the ET between normal ears and ears in patients with CSOM. Methods The MRI records of 40 patients who underwent tympanomastoidectomy for a diagnosis of CSOM were reviewed retrospectively. The healthy ears served as the control group. The length, diameter, surface area and volume of the tensor veli palatini muscle (TVPM) and levator veli palatini muscle (LVPM) were measured, in addition to the diameter of the pharyngeal orifice of the ET, volume of the Ostmann fat pad, bimucosal thickness of the lumen of the ET, and mucosal thickness. Results In the pathological ears, the mean length of the TVPM and LVPM was 22.6 mm and 19.3 mm, the mean diameter was 3.2 and 5.3 mm, and the mean volume was 1.75 and 3.2 cm(3), respectively. In addition, the mean diameter of the pharyngeal orifice of the ET was 1.9 mm. There were no significant between-group differences in the paratubal structures (p > 0.05). PMID- 27008281 TI - Usefulness of the fast spin-echo three-point Dixon (mDixon) image of the knee joint on 3.0-T MRI: comparison with conventional fast spin-echo T2 weighted image. AB - OBJECTIVE: To compare the quality of two different imaging methods, three-point Dixon (mDixon) and fast spin-echo (FSE) T2 weighted image (T2WI) [and fat suppression (FS) T2WI], and to assess the utility of mDixon for the imaging of knee joint pathology. METHODS: This retrospective study included 66 patients who underwent both mDixon and FSE T2WI (and FS T2WI) of the knee joint. Signal-to noise ratio (SNR) and contrast-to-noise ratio (CNR) of the two sequences at the articular cartilage and ligament were measured. Two radiologists independently evaluated the anatomic identification score and diagnostic performances of the two sequences. RESULTS: The mean SNRs and CNRs of the patellar cartilage, femoral cartilage and anterior cruciate ligament (ACL) were significantly higher on T2WI and FS T2WI than on mDixon imaging, with the exception of the mean SNR of ACL on in-phase images. Most of the anatomic identification scores did not show significant differences, except for inferiorities of the in-phase mDixon in the evaluation of the cruciate ligament. There were no significant differences in sensitivity, specificity and accuracy between mDixon and T2WI regarding diagnostic performance. CONCLUSION: mDixon images have equivalent anatomic identification ability with the exception of cruciate ligament delineation on in phase images and have a diagnostic performance comparable with that of FSE T2WI for meniscal, cartilage and ligament injuries of the knee joint. There would be a net saving in time, if mDixon was the only sequence used. ADVANCES IN KNOWLEDGE: The mDixon images have equivalent anatomic identification abilities, with the exception of cruciate ligament delineation on in-phase images and have a diagnostic performance comparable with that of FSE T2WI for meniscal, cartilage and ligament injuries of the knee joint. PMID- 27008282 TI - CCL25/CCR9 Signal Promotes Migration and Invasion in Hepatocellular and Breast Cancer Cell Lines. AB - Cancer is one of the most lethal diseases worldwide, and metastasis is the most common cause of patients' deaths. Identification and inhibition of markers involved in metastasis process in cancer cells are promising works to block metastasis and improve prognoses of patients. Chemokines are a superfamily of small, chemotactic cytokines, whose functions are based on interaction with corresponding receptors. It has been found that one of the functions of chemokines is to regulate migration and invasion abilities of lymphocytes, as well as cancer cells. Chemokine receptor 9 (CCR9) regulates trafficking of lymphocytes and cancer cell lines when interacting with its exclusive ligand chemokine 25 (CCL25). However, the mechanisms of CCL25/CCR9 signal that regulates metastasis of cancer cells are not completely known yet. In this study, we stimulated or inhibited CCL25/CCR9 signal in breast cancer cell line (MDA-MB-231) and hepatocellular cancer cell lines (HepG2 and HUH7), and found that CCL25/CCR9 signal resulted in different promotion of migration and invasion in different cell lines. These phenomena could be explained by selective regulation of several markers of epithelial-mesenchymal transition (EMT). Our findings suggested that CCL25/CCR9 signal may provide cancer cells with chemotactic abilities through influencing several EMT markers. PMID- 27008284 TI - Full-Endoscopic Procedures Versus Traditional Discectomy Surgery for Discectomy: A Systematic Review and Meta-analysis of Current Global Clinical Trials. AB - BACKGROUND: Traditional discectomy surgery (TDS) provides good or excellent results in clinical surgical discectomy but may induce neural adhesion, spinal structural damage, instability, and other complications. The potential advantages of full-endoscopic (FE) procedures over standard TDS include less blood loss, less postoperative pain, shorter hospitalization, and an earlier return to work. However, more evidence is needed to support this new technology in clinical applications. OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the safety and efficacy of FE and TDS. STUDY DESIGN: Comprehensive systematic review and meta-analysis of the literature. METHODS: Electronic databases, including PubMed, EMBASE, SinoMed, and Cochrane Library, were searched to identify clinical therapeutic trials comparing FE to TDS for discectomy. RESULTS: Six trials comprising 730 patients were included, and the overall quality of the literature was moderate, including 4 Grade I levels of evidence (4 randomized controlled trials, [RCTs]) and 2 Grade II levels (2 non-RCTs). The pooled data revealed no difference in reoperation rates between FE and TDS (P = 0.94), but the complication rate was significantly lower in the FE group (3.86%) than in the TDS group (11.4%). Perioperative parameters (operation time, blood loss, hospitalization time, and return to work days) were significantly lower in the FE group (P < 0.05 for all groups using either score). Postoperative pain and neurology score assessments were conducted at 4 different time points at 3 months, 6 months, 12 months, and 24 months. Significant differences were detected in the following: lumbar North American Spine Society (NASS) pain at 6 months (P = 0.008); cervical NASS neurology at 6 months (P = 0.03); visual analog scale (VAS) score in leg at 3 months (P < 0.001); VAS score in arm at 24 months (P = 0.002); VAS score in neck at 3 months, 6 months, and 12 months after therapy (P = 0.003, P = 0.004, P = 0.01); and VAS score in neck at 3 months and 6 months (P = 0.01, P = 0.004). Moreover, the pooled data revealed no statistically significant differences in improvements in the Oswestry disability index (ODI), instability (X-ray), and Hilibrand criteria (P > 0.05 for all groups). LIMITATIONS: Only 6 studies were included, 4 of which had the same authors. Between-study heterogeneity due to differences in socioeconomic factors, nutrition, and matching criteria is difficult to avoid. CONCLUSIONS: Based on this meta-analysis of 24 months of clinical results, we conclude that the FE procedure is as effective as TDS but has the additional benefits of lower complication rates and superior perioperative parameters. In addition, patients may experience less pain with FE techniques due to a smaller incision and less operative injury. However, large-volume, well-designed RCTs with extensive follow-up are needed to confirm and update the findings of this analysis. PMID- 27008285 TI - Effects of Stress and Relaxation on Central Pain Modulation in Chronic Whiplash and Fibromyalgia Patients Compared to Healthy Controls. AB - BACKGROUND: Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM. OBJECTIVES: The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals. STUDY DESIGN: A randomized crossover design was employed. SETTING: The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp. METHODS: Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched. RESULTS: A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001). LIMITATIONS: The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long term relaxation therapies. CONCLUSIONS: A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with FM, while cognitive stress and relaxation did not worsen bottom-up sensitization in chronic WAD patients and healthy persons. However, endogenous pain inhibition, assessed using a CPM paradigm, worsened in chronic WAD and FM patients, as well as in healthy people following both interventions. PMID- 27008283 TI - Adolescent Sexual Minority Girls Are at Elevated Risk for Use of Multiple Substances. AB - BACKGROUND: Sexual minority youth, especially girls, are at risk for alcohol, cigarette, and marijuana use when these substances are examined individually. However, little is known about concurrent use of these substances (i.e., three substance use) in relation to sexual orientation. OBJECTIVES: The present study compared profiles of past year alcohol, cigarette, and marijuana use between SMGs and heterosexual girls. In addition, because internalizing and externalizing symptoms are associated with substance use, we examined whether sexual orientation was associated with substance use profile over and above co-occurring psychopathology. METHODS: Mixture modeling was used to identify patterns of alcohol (including binge drinking), cigarette, and marijuana use in the past year using a cross-sectional sample of urban adolescent girls (Pittsburgh Girls Study; N = 2,064; mean age = 17). Approximately 8% (n = 173) of the girls endorsed a lesbian or bisexual identity. RESULTS: Five substance using classes were identified: low-level substance use (72%), marijuana use (5%), cigarette use (8%), alcohol use (8%), and three-substance use (7%). SMGs were at an increased risk for substance use than heterosexual girls, particularly three-substance use (OR = 6.69, p < .001), cigarette use (OR = 6.26, p < .001), and marijuana use (OR = 3.86, p < .001) classes. Substance use patterns were regressed on sexual orientation, internalizing symptoms (i.e., depression, anxiety), and externalizing symptoms (i.e., conduct problems, oppositional defiant disorder). The disparities remained robust after controlling for internalizing and externalizing symptoms. CONCLUSIONS/IMPORTANCE: Clinicians and researchers should be aware of potential three-substance use among SMGs. Substance use interventions for SMG may benefit from targeting risk factors that cut-across several substances, particularly externalizing symptoms. PMID- 27008286 TI - False Loss of Resistance in Cervical Epidural Injection: The Loss of Resistance Technique Compared with the Epidrum Guidance in Locating Epidural Space. AB - BACKGROUND: Epidural block failures can occur due to a misleading loss of resistance (LOR) signal. OBJECTIVE: This study was designed to evaluate the false LOR rate and to determine whether the Epidrum, which is an LOR device for identifying the epidural space, improves the ability to find the epidural space during cervical epidural injection compared the LOR technique. STUDY DESIGN: A randomized, single-blind trial. SETTING: Single academic medical center. METHODS: A total of 150 patients undergoing cervical interlaminar epidural injections at C7-T1 were randomized to receive either the LOR technique with a syringe (group C) or the Epidrum guidance (group E). Fluoroscopic images were used to confirm the accuracy of the needle placement within the epidural space. The rate of misleading epidural signals and adverse effects were recorded and analyzed. RESULTS: The false LOR rate was 74.7% for group C, 62.7% for group E, and 68.7% overall. The incidence of false LOR was not significantly different between the 2 groups. Also, the success rate and the rate of true epidural signals were similar between the 2 groups. LIMITATIONS: The Epidrum cannot be used to confirm whether the needle has entered the vascular space without fluoroscopy. CONCLUSIONS: In this study, we did not find any difference in accuracy between the Epidrum and the LOR technique with a syringe for detecting the cervical epidural space. The overall higher false LOR rate suggests that the combined use of fluoroscopy and LOR technique with a syringe or the Epidrum is necessary to increase the rate of finding the true cervical epidural space. CLINICAL TRIALS REGISTRATION: KCT0001333. PMID- 27008287 TI - Effect of Adding Calcitonin to Translaminar Epidural Steroid in Degenerative Lumbar Spinal Canal Stenosis. AB - BACKGROUND: Spinal canal stenosis is one of the most common causes of low back pain and disability. Its management varies from surgical to conservative, and the indications for ideal management are not clearly defined. OBJECTIVES: This study was conducted to evaluate the effect of adding calcitonin to local anesthetic and corticosteroid in epidural injection for patients suffering from degenerative lumbar spinal canal stenosis. STUDY DESIGN: Randomized double-blind clinical trial. SETTING: Hospital outpatient setting. METHODS: One hundred thirty-two patients with degenerative spinal canal stenosis were randomly allocated into 2 groups. Group I received C-arm guided epidural injection of local anesthetic and corticosteroid and Group II received 50 international unit calcitonin added to the mixture of local anesthetic and corticosteroid. Both groups received 2 sets of injections, one week apart. Visual analogue scale for pain during movement and walking distance until incidence of neurogenic claudication have been used for pain assessment, and Oswestry Low Back Pain Disability Questionnaire and analgesic consumption were evaluated for one year. RESULTS: Both groups showed comparable benefits regarding improvement in pain intensity, walking distance, Oswestry scale, and analgesic consumption during the first month follow-up period. These beneficial effects continued in calcitonin group for one year. LIMITATIONS: The present study patients would be graded as having mild or at worst moderate stenosis. So, the present study did not examine the efficacy of epidural calcitonin in severe spinal canal stenosis and did not stratify the results according to degree of stenosis which would also have been useful in determining the validity of calcitonin in different degrees of stenosis. CONCLUSION: Adding calcitonin to epidural steroid and local anesthetic injection seems to be more effective than epidural steroid and local anesthesia alone in management of spinal canal stenosis regarding increased walking distance, better Oswestry scale, diminished pain intensity and perception of paresthesia, and less analgesic consumption, all the above mentioned benefits continued up to one year. So, epidural calcitonin may be considered as a new therapeutic modality in the management of pain in spinal canal stenosis. PMID- 27008288 TI - Pain Pressure Threshold in the Region of the Sacroiliac Joint in Patients Diagnosed with Sacroiliac Joint Pain. AB - BACKGROUND: Although the prevalence of sacroiliac joint (SIJ) pain is relatively high (15 - 30%), there is no unambiguous reference standard to diagnose SIJ pain. Pressure tenderness in the SIJ region is used for diagnostic purposes, but the clinimetric properties of this procedure remain to be determined. OBJECTIVES: The aim of this study is to determine the reliability of pain pressure threshold (PPT) measurements in the SIJ region and the difference in PPTs in the SIJ region between healthy volunteers and PPTs in patients with SIJ pain. STUDY DESIGN: Prospective cohort study. SETTING: Outpatient pain clinic VU University Medical Center. METHODS: Forty-one healthy volunteers and 31 patients diagnosed with SIJ pain were included. PPTs were obtained from 5 measurement points in the region of the SIJ with a pressure pain algometer using a standardized protocol. The inter rater reliability of this method was calculated by means of the Intraclass Correlation Coefficients (ICC) of individual assessment performed by 2 individual raters of SIJs of healthy volunteers on both sides. PPTs of healthy volunteers were compared to those of the affected side in patients with SIJ pain. RESULTS: PPT measurement showed moderate to good inter-rater reliability (ICC 0.6 - 0.82).The median PPTs of 5 points was comparable for both sides in healthy volunteers (right: 8.5 kg/cm2 [IQR 6.0 - 10.0]; left 8.3 kg/cm2 (5.8 - 10.0]). Median PPTs for the affected sides of patients with SIJ pain were significantly lower compared to the same side of healthy volunteers (right: 2.4 kg/cm2 [IQR 2.2 - 3.2, n = 15]; left: 2.5 kg/cm2 [2.3 - 3.2, n = 16]; P < 0.001 for both sides). LIMITATIONS: Only the SIJ on one side of was measured in patients with SIJ pain, where both sides would be desirable. CONCLUSIONS: Pressure pain algometry appears to be a reliable method to establish differences in PPTs between healthy volunteers and patients with SIJ pain. The diagnostic accuracy of this test should be investigated further. PMID- 27008289 TI - Radiofrequency Neurolysis for Lumbar Pain Using a Variation of the Original Technique. AB - BACKGROUND: Zygapophysial joint arthrosis is a pathology related with axial lumbar pain. The most accepted treatment, after failure of medical management, is the thermal denervation of the medial branch. Nonetheless, the placement of the heat probe remains a challenge to surgeons, even when using the fluoroscope. Using a variation of Shealy's and Bogduk's original techniques, which includes ablation of the medial branch and the nerves present in the joint capsule, we hypothesize that we can obtain similar outcomes to those found in the literature. OBJECTIVE: To present the results attained over the last 8 years in the treatment of axial lumbar pain from zygapophysial joints degeneration, by employing a variation of the lumbar medial branch neurotomy technique, called 360-degree facet rhizotomy with radiofrequency. STUDY DESIGN: Retrospective evaluation. SETTING: Spine Center - Minimally Invasive Surgery in Bogota, Colombia. METHODS: A medical chart review was conducted for patients diagnosed with axial lumbar pain from zygapophysial joint arthrosis and treated with 360-degree facet rhizolysis with a high frequency radiofrequency energy source between 2008 and 2014. Data were evaluated under modified MacNab and pre- and postoperative visual analog scale (VAS) criteria. RESULTS: We obtained a total of 73 patients. The average population age was 58.6 years. The preoperative VAS obtained was 7.3, which changed to 1.7 one year after the procedure. The MacNab criteria 12 months after the surgery gave satisfactory outcomes (excellent and good) from 91.7% of the patients. LIMITATIONS: This retrospective study includes inherent limitations and only offers one year follow-up data. CONCLUSIONS: Thermal therapy for zygapophysial joint arthrosis constitutes a safe and effective technique. The one year follow-up data presented here show that the ablation of the medial branch and nerves present in the joint capsule leads to satisfactory results in a high percentage of patients. PMID- 27008290 TI - What is the Correlation Between Facet Joint Radiofrequency Outcome and Response to Comparative Medial Branch Blocks? AB - BACKGROUND: Facet joint pain is a common cause of low back pain. There are no physical exam findings that provide a reliable diagnosis. Diagnosis is made by medial branch block injections (MBB). Once the source of pain has been determined, radiofrequency neurotomy (RFN) can be performed. Previous studies have shown that RFN reduces level of pain and improves function. No study has tried to correlate MBB results with outcomes after RFN. OBJECTIVES: (1) Estimate percentage decrease in pain, decrease in analgesic use, and increase in activity tolerance after facet joint radiofrequency neurotomy (2) Determine correlation between percentage pain relief or duration of pain relief after MBB and RFN outcomes. STUDY DESIGN: Retrospective review of patients undergoing RFN, who had = 70% pain relief on 2 sets of MBB with 0.5 - 1 mL of 2% lidocaine (MBB 1) and 0.75% bupivacaine (MBB 2). IRB approval was obtained before data collection began. SETTING: All patients undergoing RFN between 12/06-1/10 at University Spine and Pain clinics. METHODS: Subgroup analysis was performed based on response to MBB, a)100% pain relief and <100% pain relief after MBB 1 and 2 and a) those with > 8 hours and = 8 hours pain relief after MBB 1 and 2. Correlational analysis was conducted to determine the correlation between a) percent pain relief after MBB1 and 2 and percent change in pain after RFN and b) duration of pain relief after MBB 1 and 2 and percent change in pain relief after RFN. OUTCOME MEASURES: Pain intensity, disability index, analgesic use, and patient perception of benefit. RESULTS: Mean improvement of Disability scores at 3 months was 12.63 (P = 0.001), percent pain relief was 47.68% (P = 0.001). Patients with 100% pain relief after MBB 1 had greater improvement of disability scores (P = 0.008). Those with > 8 hours pain relief after MBB 1 had greater reduction in pain (P = 0.014). Pearson correlation analysis showed no correlation between percent pain relief or duration of pain relief after MBB and percent pain relief after RFN. LIMITATIONS: This was a small observational study with short term follow up. CONCLUSION: Patients had improved disability scores and decreased pain after RFN. No correlation was seen between results on MBB and pain relief after RFN. It is still unclear how many medial branch blocks are needed and the criteria for MBB results before proceeding to RFN. PMID- 27008291 TI - Clinical Efficacy of Pulsed Radiofrequency Neuromodulation for Intractable Meralgia Paresthetica. AB - BACKGROUND: Meralgia paresthetica (MP) is a neurologic disorder of the lateral femoral cutaneous nerve (LFCN), which is characterized by a localized area of paresthesia and numbness on the anterolateral aspect of the thigh. In most patients with MP, symptoms can be successfully managed with conservative treatment. However, in a small group of MP patients who are refractory to medical treatment, more aggressive low-risk treatment should be considered. OBJECTIVE: The objective of this study was to evaluate clinical outcomes of pulsed radiofrequency (PRF) neuromodulation of the LFCN in MP patients refractory to conservative treatment. STUDY DESIGN: Retrospective evaluation. METHODS: We retrospectively reviewed the clinical data of 11 patients with medically intractable MP who underwent PRF neuromodulation of the LFCN. These patients with MP underwent a diagnostic LFCN block using 2.0% lidocaine. Temporary pain relief > 50% was considered to be a positive response to the diagnostic nerve block. Following a positive response to the diagnostic nerve block, patients underwent PRF neuromodulation at 42 degrees for 2 minutes. Patient pain was evaluated using a 10-cm visual analog scale (VAS). In MP patients who received PRF, we statistically evaluated VAS scores and the presence of any complications for 6 or more months after the procedure. RESULTS: The mean initial patient VAS score was 6.4 +/- 0.97 cm. This score was decreased to 0.91 +/- 0.70 cm, 0.82 +/- 0.75 cm, and 0.63 +/- 0.90 cm at the one-, 3-, and 6- month follow-ups, respectively (P < 0.001). Sixty-three point six percent of patients achieved complete pain relief (pain-free) in the last follow-up, whereas 27.3% of patients achieved successful pain relief (= 50% reduction in pain as determined by the VAS score). Furthermore, we did not observe any complications after the procedure. CONCLUSION: PRF neuromodulation of the LFCN provides immediate and long-lasting pain relief without complications. Therefore, PRF of the LCFN can be used as an alternative treatment in patients with MP who are refractory to conservative medical treatment. PMID- 27008292 TI - The Best-Laid Plans of "Back Mice" and Men: A Case Report and Literature Review of Episacroiliac Lipoma. AB - BACKGROUND: Back mice, or episacroiliac lipoma, represent a potentially treatable cause of low back pain that may be under-recognized in clinical practice. Despite being well characterized based on clinical history and physical examination findings, implementation of appropriate treatment may be delayed or missed based on a lack of familiarity with the diagnosis. OBJECTIVES: In this case report and literature review, we describe a 47-year-old woman with history of persistent low back pain who presented with a pain exacerbation consistent with a back mouse. The history, epidemiology, clinical characteristics, differential diagnosis, potential mechanisms for pain, and treatment options for back mice were then reviewed. STUDY DESIGN: Case report and literature review. SETTING: Academic university-based pain management center. RESULTS: Studies included one randomized clinical trial, 4 cross-sectional studies, 8 case reports or series, and 16 other publications prior to 1967. LIMITATIONS: A single case report. CONCLUSIONS: Firm, rubbery, mobile nodules that are located in characteristic regions of the sacroiliac, posterior superior iliac, and the lumbar paraspinal regions may represent fatty tissue that has herniated through fascial layers. When painful, these back mice may be confused with other causes of low back pain. In particular, the presence of point tenderness may mimic myofascial pain, and reports of radicular pain may imitate herniated nucleus pulposus. However, back mice may be distinguished from other entities based on findings from the history and physical examination such as absence of neurological deficit. Treatment consisting of injection of local anesthetic into the nodule with or without corticosteroid followed by repeated, direct needling has been reported to relieve pain in many case reports. The one clinical trial comparing injection of local anesthetic to normal saline, which did not include repeated needling, found only mild and transient benefit in the treatment group. PMID- 27008293 TI - Different Influences of Lipofection and Electrotransfection on In Vitro Gene Delivery to Primary Cultured Cortex Neurons. AB - BACKGROUND: Many pain states are linked to central nervous system (CNS) diseases involving the dysfunction of dendritic arborization, making restoration a promising therapeutic strategy. Transfection of primary cortex neurons offers the possibility to study mechanisms which are important for the restoration of proper arborization. Its progress is, however, limited at present due to the lack of suitable gene transfer techniques. OBJECTIVE: To obtain better insight into the transfection potential of currently used techniques, 2 non-viral transfection methods, lipofection and gene electrotransfer (GET), were compared. STUDY DESIGN: This is a comparison study performed on cultured cells. METHODS: The transfection efficiency and neuronal viability, as well as the neuronal dendritic arborization after lipofection or GET, were compared. Primary cultured cortex neurons were transfected with the pEGFP-N1 plasmid, either using Lipofectamine 2000 (2, 3, or 4uL) or with electroporation, with our previously optimized protocol (200V/25 ms). RESULTS: Transfection efficiency and cell viability were inversely proportional for lipofection. The appropriate ratio of Lipofectamine and plasmid DNA provides optimal conditions for lipofection. Although GET offered higher transfection efficiency, it could not induce complex dendritic arborization, which made it unsuitable for in vitro gene transfer into cortex neurons. LIMITATIONS: Limitations include species variability and translational applicability for CNS diseases and pain states related to potential toxicity. CONCLUSIONS: Based on these findings, lipofection might be advantageous for in vitro application to primary cultured cortex neurons. Pain states, stress mediated pathogenesis, and certain CNS diseases might potentially utilize this important technique in the future as a therapeutic modality. PMID- 27008294 TI - Successful Identification and Assessment of the Superior Cluneal Nerves with High Resolution Sonography. AB - BACKGROUND: Low back pain is a disabling and common condition, whose etiology often remains unknown. A suggested, however rarely considered, cause is neuropathy of the medial branch of the superior cluneal nerves (mSCN)-either at the level of the originating roots or at the point where it crosses the iliac crest, where it is ensheathed by an osseo-ligamentous tunnel. Diagnosis and treatment have, to date, been restricted to clinical assessment and blind infiltration with local anesthetics. OBJECTIVE: To determine whether visualization and assessment of the mSCN with high-resolution ultrasound (HRUS) is feasible. STUDY DESIGN: Interventional cadaver study and case series. METHODS: Visualization of the mSCN was assessed in 7 anatomic specimens, and findings were confirmed by HRUS-guided ink marking of the nerve and consecutive dissection. Further, a patient chart and image review was performed of patients assessed at our department with the diagnosis of mSCN neuropathy. RESULTS: The mSCN could be visualized in 12 of 14 cases in anatomical specimens, as confirmed by dissection. Nine patients were diagnosed with mSCN syndrome of idiopathic or traumatic origin. Diagnosis was confirmed in all of them, with complete resolution of symptoms after HRUS-guided selective nerve block. LIMITATIONS: These findings are first results that need to be evaluated in a systematic, prospective and controlled manner. CONCLUSION: We hereby confirm that it is possible to visualize the mSCN in the majority of anatomical specimens. The patients described may indicate a higher incidence of mSCN syndrome than has been recognized. mSCN syndrome should be considered in patients with low back pain of unknown origin, and HRUS may be able to facilitate nerve detection and US-guided nerve block. PMID- 27008295 TI - Re: Ultrasound Guided Intercostobrachial Nerve Blockade in Patients with Persistent Pain. PMID- 27008296 TI - Epidural Injections for Lumbar Radiculopathy and Spinal Stenosis: A Comparative Systematic Review and Meta-Analysis. AB - BACKGROUND: The prevalence of chronic low back pain and related disability is rapidly increasing as are the myriad treatments, including epidural injections. Even though epidural injections are one of the most commonly performed procedures in managing low back and lower extremity pain, starting in 1901 with local anesthetic alone, conflicting recommendations have been provided, despite the extensive literature. Recently Chou et al performed a technology assessment review for Agency for Healthcare Research and Quality (AHRQ) part of which was published in Annals of Internal Medicine showing lack of effectiveness of epidural steroid injections in managing lumbar radiculopathy and spinal stenosis. In contrast, multiple other publications have supported the efficacy and use of epidural injections. PURPOSE: To assess the efficacy of 3 categories of epidural injections for lumbar and spinal stenosis: performed with saline with steroids, local anesthetic alone, or steroids with local anesthetic and separate facts from opinions. DATA SOURCES: PubMed, Cochrane Library, US National Guideline Clearinghouse, prior systematic reviews, and reference lists. The literature search was performed through August 2015. STUDY SELECTION: Randomized trials, either placebo or active control, of epidural injections for lumbar radiculopathy and spinal stenosis. DATA EXTRACTION: Data extraction and methodological quality assessment were performed utilizing Cochrane review methodologic quality assessment and Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Evidence was summarized utilizing principles of best evidence synthesis. DATA SYNTHESIS: Thirty-nine randomized controlled trials met inclusion criteria. There were 9 placebo controlled trials evaluating epidural corticosteroid injections, either with sodium chloride solution or bupivacaine, compared to placebo injections. There were 12 studies comparing local anesthetic alone to local anesthetic with steroid. RESULTS: A meta-analysis of 5 studies utilizing sodium chloride or bupivacaine with steroid showed a lack of efficacy.A comparison of lidocaine to lidocaine with steroids in 7 studies showed significant effectiveness from baseline to long-term follow-up periods. Meta-analysis showed a similar effectiveness for pain and function without non-inferiority of lidocaine compared to lidocaine with steroid at 3 months and 12 months. LIMITATIONS: The review was restricted to the data available with at least 3 months of follow-up, which excluded some studies. The inclusion criteria were restricted to English language studies. CONCLUSION: Epidural corticosteroid injections for radiculopathy or spinal stenosis with sodium chloride solution or bupivacaine were shown to be ineffective. Lidocaine alone or lidocaine in conjunction with steroids were significantly effective. PMID- 27008297 TI - Effect of 3 Different Doses of Intrathecal Dexmedetomidine (2.5ug, 5ug, and 10 ug) on Subarachnoid Block Characteristics: A Prospective Randomized Double Blind Dose-Response Trial. AB - BACKGROUND: The extended analgesic efficacy of intrathecal dexmedetomidine (ITD) has been investigated in a few clinical trials; however, there is a lack of conclusive evidence upon its ideal dosage. OBJECTIVES: To elucidate the dose response relationship between ITD and subarachnoid block characteristics, particularly the duration of analgesia and differential analgesia (DA: defined as time difference from the offset of motor blockade to the first analgesic requirement on numerical rating scale = 4.0). STUDY DESIGN: Prospective, randomized double blind active control trial. SETTING: Medical college teaching hospital. METHODS: Ninety adult (18 - 60 years) patients undergoing elective lower abdominal and lower limb surgeries were randomized into 3 groups to receive intrathecal 0.5% bupivacaine 3 mL with 2.5 ug (group BD2.5), 5ug (group BD5), or 10 ug (group BD10) dexmedetomidine in 0.5 mL normal saline. The 2 segment sensory regression times (TSSRT), duration of motor blockade analgesia, DA, and perioperative adverse effects were assessed. The primary outcome was duration of analgesia and DA. STATISTICS: ANOVA, Kruskal Wallis test, Chi-square (x2), and Fisher's exact test, significance: P < 0.05. RESULTS: The onset of sensory block was significantly earlier in group BD10 compared with group BD5 (P = 0.035) and BD2.5 (P = 0.010) while the onset of motor block was significantly earlier in group BD10 compared with BD2.5 (P = 0.020). There was a significant and dose dependent prolongation of the duration of sensory block (127.50, 149.17, and 187.50 minutes; P < 0.001), motor block (258.50, 331, and 365 minutes; P < 0.001), analgesia (306.17, 396.50, and 512 minutes; P < 0.001), and DA (47.67, 65.50, and147 minutes; P < 0.001) with escalating doses of ITD, respectively. Group BD10 required significantly fewer rescue analgesics compared with other 2 groups (P = 0.001). Except for mild sedation which was significantly higher in group BD10; all the groups were comparable with respect to hemodynamic and other adverse effects. LIMITATIONS: Lack of placebo group, exclusion of higher doses (15ug) of ITD, and short duration of postoperative follow-up. CONCLUSIONS: The addition of 10 ug compared with 2.5 ug or 5ug ITD to 0.5% hyperbaric bupivacaine is associated with significantly earlier onset of sensory and motor block as well as prolonged duration of sensory block, motor block, analgesia, and DA with a comparable adverse effect profile. PMID- 27008298 TI - A Typology of Predictive Risk Factors for Non-Adherent Medication-Related Behaviors among Chronic Non-Cancer Pain Patients Prescribed Opioids: A Cohort Study. AB - BACKGROUND: There has been no previous prospective examination of the homogeneity of chronic non-cancer pain (CNCP) patients in risk factors for non-adherent opioid use. OBJECTIVES: To identify whether latent risk classes exist among people with CNCP that predict non-adherence with prescribed opioids. STUDY DESIGN: Prospective cohort study. METHODS: The Pain and Opioids IN Treatment prospective cohort comprises 1,514 people in Australia prescribed pharmaceutical opioids for CNCP interviewed 3 months apart. Risk factors were assessed in wave 1, and non-adherent behaviors in the 3 months prior to wave 1 and wave 2. Latent class analysis was used to examine groups with differing risk profiles. Logistic regression was used to examine predictors of non-adherence. RESULTS: A 4-class model was selected with classes described as: 1) Poor Physical Functioning group (27%); 2) Poor Coping/Physical Functioning group (35%); 3) Substance Use Problems group (14%); and 4) Multiple Comorbid Problems group (25%). The latter 2 groups had an increased risk of requesting increased opioid doses, early script renewals, using diverted medication, dose stock-piling, and unsanctioned dose alteration at wave 2. LIMITATIONS: Risk factor onset prior to non-adherent behavior cannot be determined. CONCLUSIONS: Clusters of CNCP patients with distinct risk profiles for non-adherence exist. Each group was identified by at least one risk factor but the likelihood of non-adherent opioid use was higher in groups with particular clusters of multiple risk factors. Not all those with risk factors display non-adherence, emphasising the need for strategies to reduce risk for those patients displaying particular clusters of risks. PMID- 27008299 TI - Analgesic Effects and Neuropathology Changes of Electroacupuncture on Curing a Rat Model of Brachial Plexus Neuralgia Induced by Cobra Venom. AB - BACKGROUND: Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. OBJECTIVE: To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. STUDY DESIGN: Controlled animal study. SETTING: Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. METHODS: Sixty-six adult male Sprague Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 - 1.5 - 2 mA) was applied to the right "Shousanli" (LI10) and "Quchi" (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. RESULTS: Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not demonstrate significant differences. Meanwhile, on day 12 after surgery it was observed under light microscopy that the inflammatory response in the right brachial plexus and cervical cord (C8-T1) were significantly attenuated after EA stimulation. Furthermore, the demyelination of the brachial plexus and cervical cord (C8-T1) were also reversed. LIMITATIONS: Limitations include the fact that there was demyelination of the cervical cord (C8-T1) in the control group because of inappropriate manipulation. CONCLUSION: Repeated EA contributes significant analgesic effects in the treatment of BPN. PMID- 27008300 TI - Pudendal Neuralgia Due to Pudendal Nerve Entrapment: Warning Signs Observed in Two Cases and Review of the Literature. AB - Pudendal neuralgia is a chronic neuropathic pelvic pain that is often misdiagnosed and inappropriately treated. The Nantes criteria provide a basis for the diagnosis of pudendal neuralgia due to pudendal nerve entrapment. The 5 essential diagnostic criteria are pain situated in the anatomical territory of the pudendal nerve, worsened by sitting, the patient is not woken at night by the pain, and no objective sensory loss is detected on clinical examination. The fifth criterion is a positive pudendal nerve block. We have also clarified a number of complementary diagnostic criteria and several exclusion criteria that make the diagnosis unlikely. When pudendal neuralgia due to pudendal nerve entrapment is diagnosed according to the Nantes criteria, no further investigation is required and medical or surgical treatment can be proposed. Nevertheless, a number of warning signs suggesting other possible causes of pudendal neuralgia must not be overlooked. These warning signs (red flags) are waking up at night, excessively neuropathic nature of the pain (for example, associated with hypoesthesia), specifically pinpointed pain, which can suggest neuroma and pain associated with neurological deficit. In these atypical presentations, the diagnosis of pain due to pudendal nerve entrapment should be reconsidered and a radiological examination should be performed. The 2 cases described in this report (tumor compression of the pudendal nerve) illustrate the need to recognize atypical pudendal neuralgia and clarify the role of pelvic magnetic resonance imaging (MRI), as MRI provides very valuable information for the evaluation of diseases involving the ischiorectal fossa. The presence of red flags must be investigated in all cases of pudendal neuralgia to avoid missing pudendal neuralgia secondary to a mechanism other than nerve entrapment. PMID- 27008301 TI - Motor Neuron Diseases Accompanying Spinal Stenosis: A Case Study. AB - A 75-year-old man, who was healthy, visited the hospital because of shooting pain and numbness in both lower limbs (right > left). The patient had an L4/5 moderate right foraminal stenosis and right subarticular disc protrusion and received a lumbar epidural block. The patient experienced severe weakness in the right lower limb after 2 days. Lumbar and cervical magnetic resonance images were taken and electromyography and a nerve conduction study were performed to arrive at the diagnosis of a motor neuron disease. The patient expired 4 months later with respiratory failure due to motor neuron disease. This case suggests that any abnormal neurological symptoms that occur after an epidural block should be examined thoroughly via testing and consultations to identify the cause of the symptoms. PMID- 27008302 TI - Combined Spinal Cord Stimulation and Peripheral Nerve Stimulation for Brachial Plexopathy: A Case Report. AB - Brachial plexopathy usually results from an iatrogenic brachial plexus injury and can sometimes cause severe chronic pain and disability. There are a number of possible treatments for this condition, including medication, physical therapy, nerve blocks, and neuromodulation, but they are not always successful. Recently, combined spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) have been tried for various chronic pain diseases because of their different mechanisms of action.Here, we describe the case of a 54-year-old man who was diagnosed with brachial plexopathy 8 years ago. He underwent video-assisted thoracoscopic surgery to remove a superior mediastinal mass. However, his brachial plexus was damaged during the surgery. Although he had received various treatments, the pain did not improve. For the management of intractable severe pain, he underwent SCS 2 years ago, which initially reduced his pain from numeric rating scale (NRS) 10/10 to NRS 4 - 5/10, but the pain then gradually increased, reaching NRS 8/10, 6 months ago. At that time, he was refractory to other treatments, and we therefore applied PNS in combination with SCS. The PNS electrode was positioned on the radial nerve under ultrasound guidance. After combined PNS and SCS, his background pain disappeared, although a breakthrough pain (NRS 3 - 4/10) was caused intermittently by light touch. Furthermore, the patient's need for analgesics decreased, and he was satisfied with the outcome of this combined treatment. We concluded that combined SCS and PNS is a very useful treatment modality, which can stimulate the target nerve both directly and indirectly, and hence, relieve pain from brachial plexopathy. PMID- 27008303 TI - Multi-Modal Treatment Approach to Painful Rib Syndrome: Case Series and Review of the Literature. AB - BACKGROUND: Mechanical chest wall pain is a common presenting complaint in the primary care office, emergency room, and specialty clinic. Diagnostic testing is often expensive due to similar presenting symptoms that may involve the heart or lungs. Since the chest wall biomechanics are poorly understood by many clinicians, few effective treatments are offered to patients with rib-related acute pain, which may lead to chronic pain. OBJECTIVE: This case series and literature review illustrates biomechanics involved in the pathogenesis of rib related chest wall pain and suggests an effective multi-modal treatment plan using interventional techniques with emphasis on manual manipulative techniques. STUDY DESIGN: Case series and literature review. SETTING: Pain clinic in an academic medical center. RESULTS: This is a case series of 3 patients diagnosed with painful rib syndrome using osteopathic palpatory physical examination techniques. Ultrasound-guided intercostal nerve blocks were followed by manual manipulation of mechanically displaced ribs as a part of our multi-modal treatment plan. A review of the literature was undertaken to clarify nomenclature used in the description of rib-related pain, to describe the biomechanics involved in the pathogenesis of mechanical rib pain, and to illustrate the use of effective manual manipulation techniques. LIMITATION: This review is introductory and not a complete review of all manual or interventional pain management techniques applicable to the treatment of mechanical rib-related pain. CONCLUSIONS: Manual diagnostic and therapeutic skills can be learned by physicians to treat biomechanically complex rib-related chest wall pain in combination with interventional image-guided techniques. Pain physicians should learn certain basic manual manipulation skills both for diagnostic and therapeutic purposes. PMID- 27008304 TI - Percutaneous Sacroplasty under Fluoroscopic Guidance Combined with Epidurogram for Sacral Insufficiency Fracture Resulting from Metastatic Tumor and Osteoporosis. AB - Sacral insufficiency fracture resulting from a metastatic tumor or an osteoporotic fracture causes severe low back pain and radiating pain mass effect on neural foramen and chemical irritants. Percutaneous sacroplasty is one of the effective treatment modalities for sacral insufficiency fracture and its pain. Because of the structural complexity of the sacrum, obtaining an epidurogram of the S1 and S2 nerve roots before the start of the procedure can be helpful to avoid nerve injury. We present 2 successful cases of percutaneous sacroplasty performed under fluoroscopic guidance. A 65-year-old man with sacral metastasis from stomach cancer and a 52-year-old man with sacral insufficiency fracture were suffering from severe buttock pain and radiating pain. After epidurography of the S1 and S2 nerve roots with steroid and contrast dye, percutaneous sacroplasty with fluoroscopy on the S1 or S2 body and alae was performed on both patients. There was no cement leakage or any other major complications. Both patients experienced significant reduction in pain. PMID- 27008305 TI - Serratus Plane Block for Persistent Pain after Partial Mastectomy and Axillary Node Dissection. AB - Persistent pain after breast cancer surgery (PPBCS) is defined as chronic neuropathic pain that persists for more than 3 months after surgery. The pain can be sufficiently severe to cause long-term disabilities and interfere with sleep and daily life. Serratus plane block (SPB) is a novel, ultrasound-guided regional anesthetic technique that is suggested to achieve complete anesthesia of the anterolateral chest wall. Here, we demonstrate the efficacy of SPB as one of the treatment modalities for patients with PPBCS. A 73-year-old woman underwent a left partial mastectomy and axillary node dissection for breast cancer. Four months after surgery, she experienced burning pain with nocturnal exacerbation rated 10/10 on a numerical rating scale (NRS), hot flashes, numbness, and hyperesthesia of the left axilla. Pharmacological therapy did not improve her symptoms, and 15 months after the surgery, she experienced depression. We treated her with SPB with 10 mL of 1% lidocaine; this treatment was repeated 10 times over 6 months at 2- to 4-week intervals and she was simultaneously treated with pharmacological, physical, and cognitive behavioral therapy. With her improved pain control, she was able to perform physical therapy and subsequently experienced marked improvement in her functional status and ability to perform daily activities. She has not required any interventional pain management since the last SPB performed 11 months ago. SPB represents one of the treatment modalities for PPBCS and is an advantageous technique because it can be performed more safely and easily than neuraxial approaches. PMID- 27008306 TI - Spinal Cord Stimulation for Complex Regional Pain Syndrome: A Case Study of a Pregnant Female. AB - BACKGROUND: Spinal cord stimulation (SCS) is a form of neuromodulation, used to treat chronic neuropathic pain refractory to conventional medical management. Spinal cord stimulators are treatment options when intractable chronic pain has not responded to more conventional treatment modalities. Currently, the use of SCS is contraindicated in pregnancy. Nevertheless, many SCS/neuromodulation recipients are women of child bearing age who may become pregnant. There are no published reports that focus on the possible side effects of SCS or neuromodulation therapy on human fertility, fetal development, pregnancy, delivery, or lactation. OBJECTIVES: The purpose of this current report is to present a case study on the use of SCS/neuromodulation during pregnancy. STUDY DESIGN: Presentation of the case of a 24 year old female who became pregnant after receiving an SCS implantation for pain control secondary to complex regional pain syndrome (CRPS). The SCS was in use at the time of conception but deactivated when patient became aware of her pregnancy and intermittently reactivated for five minute intervals throughout the entire pregnancy. RESULTS: Currently very little documented evidence is available regarding the safety of using a SCS/neuromodulator during pregnancy; therefore its use during pregnancy is contraindicated. Available literature suggests that, women who have chosen to keep the SCS/neuromodulator activated during pregnancy have delivered healthy babies without any life threatening complications. LIMITATIONS: Case presentations do not provide conclusive evidence of treatment effectiveness. This data is only preliminary and future studies should be used to assess outcomes and measures to provide quantification of the SCS implantation during pregnancy. CONCLUSIONS: Women of child bearing age who are recipients of SCS/neuromodulation implantation should be informed of the limited knowledge available regarding the impact of SCS/neuromodulation use during pregnancy. For current recipients, decisions about ongoing use during pregnancy should be an individual decision based on the potential risks and benefits. PMID- 27008307 TI - The Treatment of Chronic Neuropathic Pain: Bio (Regenerative) Pain Treatment through Lipofilling. A Short Communication Case Series. AB - The following case series describes the treatment of neuropathic pain in post surgical scars, using adipocytes and adipose-derived stem/progenitor cells (ASCs). Two cases are described in which patients underwent lipofilling to treat painful scars after cosmetic surgery. The primary indication for lipofilling was pain reduction and not improved cosmesis. Numeric rating scale (NRS) values were reported before the intervention and at regular intervals after the lipofilling. We found a notable long-lasting reduction in the NRS values after the "modified" lipofilling treatment. The results are promising and reinforce earlier data on the positive effect of lipofilling and pain in scars. PMID- 27008308 TI - Thoracic Nerve Root Entrapment by Intrathecal Catheter Coiling: Case Report and Review of the Literature. AB - BACKGROUND: Intrathecal catheter placement has long-term therapeutic benefits in the management of chronic, intractable pain. Despite the diverse clinical applicability and rising prevalence of implantable drug delivery systems in pain medicine, the spectrum of complications associated with intrathecal catheterization remains largely understudied and underreported in the literature. OBJECTIVE: To report a case of thoracic nerve root entrapment resulting from intrathecal catheter migration. STUDY DESIGN: Case report. SETTING: Inpatient hospital service. RESULTS/ CASE REPORT: A 60-year-old man status post implanted intrathecal (IT) catheter for intractable low back pain secondary to failed back surgery syndrome returned to the operating room for removal of IT pump trial catheter after experiencing relapse of preoperative pain and pump occlusion. Initial attempt at ambulatory removal of the catheter was aborted after the patient reported acute onset of lower extremity radiculopathic pain during the extraction. Noncontrast computed tomography (CT) subsequently revealed that the catheter had ascended and coiled around the T10 nerve root. The patient was taken back to the operating room for removal of the catheter under fluoroscopic guidance, with possible laminectomy for direct visualization. Removal was ultimately achieved with slow continuous tension, with complete resolution of the patient's new radicular symptoms. LIMITATIONS: This report describes a single case report. CONCLUSION: This case demonstrates that any existing loops in the intrathecal catheter during initial implantation should be immediately re addressed, as they can precipitate nerve root entrapment and irritation. Reduction of the loop or extrication of the catheter should be attempted under continuous fluoroscopic guidance to prevent further neurosurgical morbidity. PMID- 27008309 TI - Bipolar Radiofrequency Neurotomy to Treat Neck and Back Pain in Patients with Automatic Implantable Cardioverter Defibrillator. AB - We report 2 cases of successful treatment of neck and back pain with bipolar radiofrequency ablation (RFA) of the cervical and lumbar facet joints in patients with an automatic implantable cardioverter defibrillator (AICD).Two patients with complex cardiac histories and AICD devices were treated with bipolar RFA of the facet joints. One presented with axial neck pain and the other with axial back pain. The histories and physical examinations were consistent with facetogenic pain. Diagnostic medial branch block resulted in more than 70% pain relief lasting for several days, allowing patients to perform routine daily activities without significant pain. However, we were concerned about the use of conventional RFA of the medial branches of nerves for the fear of interference with the function of AICD by the RF currents and energy. We took advantage of the localized and limited current of bipolar RFA to perform this procedure for the cervical or lumbar facet joints avoiding any interference with the function of AICD. The procedures provided long-term pain relief to the patients, and marked improvement in their functional status without any evident complications related to the function of their AICD.This case report describes the safe and successful completion of bipolar RFA of the medial branch nerves to treat cervical and lumbar facetogenic pain in patients with AICD. This modality of treatment may be considered in patients with AICD. We are finding it to be increasingly common that patients who present with chronic neck and back pain have AICDs in place. PMID- 27008310 TI - Severe Scapular Pain Following Unintentional Cervical Epidural Air Injection. AB - This a unique case of severe scapular pain following unintentional epidural space air injection during epidural steroid injection.A 70-year-old woman presented for a fluoroscopically guided C7-T1 interlaminar epidural steroid injection. Three injection attempts were made using the loss of resistance with air technique. On the first attempt the epidural space was entered, but contrast injection showed that the needle was intravenous. On the second attempt an equivocal loss of resistance with air was perceived and 5 mL of air was lost from the syringe. The needle was withdrawn and redirected, and upon the third needle passage the contrast injection showed appropriate epidural space filling up to the C4-5 level. Injection of betamethasone mixed in lidocaine was initially uneventful.However, 20 minutes post-injection the patient experienced sudden sharp and continuous pain along the medial edge of the scapula. After failing to respond to multiple intravascular analgesics, the patient was transferred to the emergency room. Her pain subsided completely following an intravenous diazepam injection. Cervical spine computerized tomography showed obvious air in the posterior epidural space from C4-5 to C6-7 as well as outside the spinal canal from (C4-T2). Having recovered fully, she was discharged the following morning. In reviewing the procedure, the equivocal loss of resistance on the second passage was actually a true loss of resistance to epidural space and air was unintentionally injected. Surprisingly, severe scapular pain resulted in a delayed manner after the steroid solution was injected. The authors theorize that unintentional prefilling of the epidural space with air prior to the injection of the subsequent steroid mixture added sufficient pressure to the epidural space to cause right-sided C4 nerve root stretching/entrapment and ensuing radicular pain to the right scapular border. The subsequent intravenous diazepam provided cervical muscle relaxation and facilitated foramina passage of air out of the spinal canal.This case demonstrates that under certain conditions entry of air into cervical epidural space can lead to unexpected, albeit temporary, neurological symptoms. PMID- 27008312 TI - Polyesters Based on Linoleic Acid for Biolubricant Basestocks: Low-Temperature, Tribological and Rheological Properties. AB - Presently, plant oils which contain high percentage of linoleic acid 1 are perceived to be a viable alternative to mineral oil for biolubricant applications due to their biodegradability and technical properties. In order to get biodegradable lubricant, triester derivatives compounds (1-5) were synthesized and characterized. The processes involved were monoepoxidation of linoleic acid 2, oxirane ring opening 3, esterification 4 and acylation 5. The structures of the products were confirmed by FTIR, 1H and 13C-NMR and LC-MS. The results that showed lowest temperature properties were obtained for triester 5, with a pour point value (PP) of -73 degrees C, highest onset temperature (260 degrees C) and lowest volatility at 0.30%. Viscosity index (VI) increased for the ester's synthetic compounds (2, 3, 4, 5), while the PP decreased. This behavior is the result of the increase of the chain length of the branching agents. Triester based linoleic acid has improved properties such as low-temperature and tribological properties. These results will make it feasible for plant oil to be used for biolubricants, fuels in chain saws, transmission oil and brake fluid. PMID- 27008311 TI - Pulmonary hypertension associated with thalassemia syndromes. AB - Chronic hemolytic anemia has increasingly been identified as an important risk factor for the development of pulmonary hypertension (PH). Within the thalassemia syndromes, there are multiple mechanisms, both distinct and overlapping, by which PH develops and that differ among beta-thalassemia major or intermedia patients. PH in beta-thalassemia major correlates with the severity of hemolysis, yet in patients whose disease is well treated with chronic transfusion therapy, the development of PH can be related to cardiac dysfunction and the subsequent toxic effects of iron overload rather than hemolysis. beta-Thalassemia intermedia, on the other hand, has a higher incidence of PH owing to the low level of hemolysis that exists over years without the requirement for frequent transfusions, while splenectomy is shown to play an important role in both types. Standard therapies such as chronic transfusion have been shown to mitigate PH, and appropriate chelation therapy can avoid the toxic effects of iron overload, yet is not indicated in many patients. Limited evidence exists for the use of pulmonary vasodilators or other therapies, such as l-carnitine, to treat PH associated with thalassemia. Here, we review the most recent findings regarding the pathogenic mechanisms, epidemiology, presentation, diagnosis, and treatment of PH in thalassemia syndromes. PMID- 27008313 TI - New Respiratory Inductive Plethysmography (RIP) Method for Evaluating Ventilatory Adaptation during Mild Physical Activities. AB - The pneumotachometer is currently the most accepted device to measure tidal breathing, however, it requires the use of a mouthpiece and thus alteration of spontaneous ventilation is implied. Respiratory inductive plethysmography (RIP), which includes two belts, one thoracic and one abdominal, is able to determine spontaneous tidal breathing without the use of a facemask or mouthpiece, however, there are a number of as yet unresolved issues. In this study we aimed to describe and validate a new RIP method, relying on a combination of thoracic RIP and nasal pressure signals taking into account that exercise-induced body movements can easily contaminate RIP thoracic signals by generating tissue motion artifacts. A custom-made time domain algorithm that relies on the elimination of low amplitude artifacts was applied to the raw thoracic RIP signal. Determining this tidal ventilation allowed comparisons between the RIP signal and simultaneously-recorded airflow signals from a calibrated pneumotachometer (PT). We assessed 206 comparisons from 30 volunteers who were asked to breathe spontaneously at rest and during walking on the spot. Comparisons between RIP signals processed by our algorithm and PT showed highly significant correlations for tidal volume (Vt), inspiratory (Ti) and expiratory times (Te). Moreover, bias calculated using the Bland and Altman method were reasonably low for Vt and Ti (0.04 L and 0.02 s, respectively), and acceptable for Te (<0.1 s) and the intercept from regression relationships (0.01 L, 0.06 s, 0.17 s respectively). The Ti/Ttot and Vt/Ti ratios obtained with the two methods were also statistically correlated. We conclude that our methodology (filtering by our algorithm and calibrating with our calibration procedure) for thoracic RIP renders this technique sufficiently accurate to evaluate tidal ventilation variation at rest and during mild to moderate physical activity. PMID- 27008315 TI - Myocardial extracellular volume fraction measurement in chronic total coronary occlusion: Association with myocardial injury, angiographic collateral flow, and functional recovery. AB - PURPOSE: To investigate whether myocardial extracellular volume fraction (ECV) measurement by cardiac MR is indicative of myocardial injury, angiographic collateral flow, and functional recovery in patients with chronic total coronary occlusion (CTO). MATERIALS AND METHODS: A total of 50 CTO patients undergoing 1.5 Tesla MR were prospectively enrolled, and 28 underwent a second MR 6 months after revascularization. T1-mapping based indices, including pre- and postcontrast T1 values and ECV, were obtained from infarcted and non-infarcted myocardium, myocardial segments, and coronary territory. The severity of myocardial injury was rated by transmurality extent of infarction (TEI) and regional wall motion abnormalities (RWMA) score. Angiographic collateral flow was evaluated using Rentrop classification. Improvement in segmental wall motion at 6 months was also assessed. RESULTS: ECV and postcontrast T1 value significantly outperformed precontrast T1 value for identifying myocardial infarction (area under the receiver operating characteristic curve [AUC]: 0.998 and 0.953 versus 0.824, all P < 0.02). Myocardial ECV was strongly correlated with TEI (P = 0.000), RWMA score (P = 0.000), and collateral classification (P = 0.007 for left anterior descending artery [LAD] territory, P = 0.001 for non-LAD territory). Furthermore, the likelihood of functional recovery was better predicted by ECV than by late gadolinium enhancement (LGE) (AUC: 0.76 versus 0.68, P < 0.02). CONCLUSION: Myocardial ECV may be a useful surrogate to assess myocardial injury and angiographic collateral flow in CTO, and ECV provides incremental value to LGE in assessing functional recovery after revascularization. J. MAGN. RESON. IMAGING 2016;44:972-982. PMID- 27008314 TI - DNA Methylation and Potential for Epigenetic Regulation in Pygospio elegans. AB - Transitions in developmental mode are common evolutionarily, but how and why they occur is not understood. Developmental mode describes larval phenotypes, including morphology, ecology and behavior of larvae, which typically are generalized across different species. The polychaete worm Pygospio elegans is one of few species polymorphic in developmental mode, with multiple larval phenotypes, providing a possibility to examine the potential mechanisms allowing transitions in developmental mode. We investigated the presence of DNA methylation in P. elegans, and, since maternal provisioning is a key factor determining eventual larval phenotype, we compared patterns of DNA methylation in females during oogenesis in this species. We demonstrate that intragenic CpG site DNA methylation and many relevant genes necessary for DNA methylation occur in P. elegans. Methylation-sensitive AFLP analysis showed that gravid females with offspring differing in larval developmental mode have significantly different methylation profiles and that the females with benthic larvae and non reproductive females from the same location also differ in their epigenetic profiles. Analysis of CpG sites in transcriptome data supported our findings of DNA methylation in this species and showed that CpG observed/expected ratios differ among females gravid with embryos destined to different developmental modes. The differences in CpG site DNA methylation patterns seen among the samples suggest a potential for epigenetic regulation of gene expression (through DNA methylation) in this species. PMID- 27008317 TI - New Insights into Electrochemical Lithiation/Delithiation Mechanism of alpha-MoO3 Nanobelt by in Situ Transmission Electron Microscopy. AB - The alpha-MoO3 nanobelt has great potential for application as anode of lithium ion batteries (LIBs) because of its high capacity and unique one-dimensional layer structure. However, its fundmental electrochemical failure mechanism during first lithiation/delithiation process is still unclear. Here, we constructed an electrochemical setup within alpha-MoO3 nanobelt anode inside a transmission electron microscope to observe in situ the mircostructure evolution during cycles. Upon first lithiation, the alpha-MoO3 nanobelt converted into numerous Mo nanograins within the Li2O matrix, with an obvious size expansion. Interestingly, alpha-MoO3 nanobelt was found to undergo a two-stage delithiation process. Mo nanograins were first transformed into crystalline Li(1.66)Mo(0.66)O2 along with the disappearance of Li2O and size shrink, followed by the conversion to amorphous Li2MoO3. This irreversible phase conversion should be responsible for the large capacity loss in first cycle. In addition, a fully reversile phase conversion between crystalline Mo and amorphous Li2MoO3 was revealed accompanying the formation and disapperance of the Li2O layer during the subsequent cycles. Our experiments provide direct evidence to deeply understand the distinctive electrochemical lithiation/delithiation behaviors of alpha-MoO3 nanobelt, shedding light onto the development of alpha-MoO3 anode for LIBs. PMID- 27008318 TI - Asymmetric Three-Component Coupling Reaction of Alkyne, Enone, and Aldehyde Catalyzed by Chiral Phebox Ruthenium Catalysts. AB - Catalytic asymmetric three-component coupling reactions of terminal alkynes, alpha,beta-unsaturated ketones, and aldehydes were studied. The chiral ruthenium complexes containing bis(oxazolinyl)phenyl ligands were found to serve as efficient catalysts for a tandem reaction based on conjugate addition of terminal alkynes to alpha,beta-unsaturated ketones and subsequent aldol reaction with aldehydes, giving beta-hydroxyketone derivatives containing alpha-propargyl groups in high yields with moderate to good enantioselectivities. This method can produce various functional molecules from commercially available substrates in a one-pot procedure. The absolute configuration of the major product was determined by X-ray analysis. The control experiments suggested that a ruthenium enolate species generated in situ by conjugate addition could be involved as an intermediate for the aldol coupling with an aldehyde. PMID- 27008319 TI - Gallbladder Sludge in Dogs: Ultrasonographic and Clinical Findings in 200 Patients. AB - Echogenic luminal contents are often noted during ultrasonographic examination of the gallbladder (GB) in canine patients, but the significance of biliary sludge is not well understood. GB contents were evaluated during 200 sequential ultrasonographic scans performed at a veterinary school, and sludge was quantified using a 1-5 scale. GB volume was retrospectively estimated from stored images. Medical records were used to determine patient demographics, clinicopathologic findings, and diagnoses/disorders. The majority of dogs (66.5%) had some hyperechoic material within the GB. Four dogs were diagnosed with a mucocele. For statistical purposes, dogs with uniformly nonechogenic bile or minimal sludge (80.5%) were compared to those with >25% sludge (17.5%). Dogs with >25% sludge were significantly older than those with minimal sludge (8 versus 11 yr). Serum cholesterol and bilirubin concentrations and activities of both alkaline phosphatase and gamma-glutamyl transferase were not correlated with the presence of GB sludge. Dogs with spontaneous hyperadrenocorticism or hypothyroidism were more likely to have >25% sludge (odds ratio: 5.04). In addition, >25% sludge was associated with increased GB volume, suggesting that changes in GB function or contractility may impact the formation of biliary sludge in dogs. PMID- 27008316 TI - CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies. AB - Many B-cell acute and chronic leukaemias tend to be resistant to killing by natural killer (NK) cells. The introduction of chimeric antigen receptors (CAR) into T cells or NK cells could potentially overcome this resistance. Here, we extend our previous observations on the resistance of malignant lymphoblasts to NK-92 cells, a continuously growing NK cell line, showing that anti-CD19-CAR (alphaCD19-CAR) engineered NK-92 cells can regain significant cytotoxicity against CD19 positive leukaemic cell lines and primary leukaemia cells that are resistant to cytolytic activity of parental NK-92 cells. The 'first generation' CAR was generated from a scFv (CD19) antibody fragment, coupled to a flexible hinge region, the CD3zeta chain and a Myc-tag and cloned into a retrovirus backbone. No difference in cytotoxic activity of NK-92 and transduced alphaCD19 CAR NK-92 cells towards CD19 negative targets was found. However, alphaCD19-CAR NK-92 cells specifically and efficiently lysed CD19 expressing B-precursor leukaemia cell lines as well as lymphoblasts from leukaemia patients. Since NK-92 cells can be easily expanded to clinical grade numbers under current Good Manufactoring Practice (cGMP) conditions and its safety has been documented in several phase I clinical studies, treatment with CAR modified NK-92 should be considered a treatment option for patients with lymphoid malignancies. PMID- 27008320 TI - Canine Osteosarcoma Treated by Post-Amputation Sequential Accelerated Doxorubicin and Carboplatin Chemotherapy: 38 Cases. AB - Canine appendicular osteosarcoma is an important clinical problem in veterinary medicine. Current standard therapy includes amputation followed by chemotherapy, which improves outcomes; however the percentage of long-term survival is still relatively low at 15-20%. Established prognostic factors include serum alkaline phosphatase level, histologic grade, and lymphocyte and monocyte counts. We used a protocol with shorter inter-treatment intervals than standard, but which we expected to still be well-tolerated, based on drugs known to be active agents, with the aim of improving outcomes by increasing dose intensity. Thirty-eight dogs with confirmed appendicular osteosarcoma and no pulmonary metastases that underwent amputation followed by this chemotherapy protocol were retrospectively evaluated. The median survival time was 317 days and 1- and 2-yr survival percentages were 43.2% and 13.9%, respectively. Toxicity was comparable to that seen with other standard dose protocols, with 5.2% of dogs hospitalized for complications that resolved with supportive care and no chemotherapy-related mortality. Serum alkaline phosphatase level (normal or high) (p = 0.004) and whether or not chemotherapy was completed (p = 0.001) were found to significantly impact survival time on multivariate analysis. Outcomes were similar to those reported with most other published chemotherapy protocols for dogs with this disease. PMID- 27008321 TI - Minimally Invasive Drainage of a Post-Laminectomy Subfascial Seroma with Cervical Spinal Cord Compression. AB - A 14 mo old female neutered Doberman pinscher was evaluated for difficulty in rising, a wide based stance, pelvic limb gait abnormalities, and cervical pain of 2 mo duration. Neurologic examination revealed pelvic limb ataxia and cervical spinal hyperesthesia. Spinal reflexes and cranial nerve examination were normal. The pathology was localized to the C1-C5 or C6-T2 spinal cord segments. Computed tomography (CT) findings indicated bony proliferation of the caudal articular processes of C6 and the cranial articular processes of C7, resulting in bilateral dorsolateral spinal cord compression that was more pronounced on the left side. A limited dorsal laminectomy was performed at C6-C7. Due to progressive neurological deterioration, follow-up CT examination was performed 4 days postoperatively. At the level of the laminectomy defect, a subfacial seroma had developed, entering the spinal canal and causing significant spinal cord compression. Under ultrasonographic guidance a closed-suction wound catheter was placed. Drainage of the seroma successfully relieved its compressive effects on the spinal cord and the patient's neurological status improved. CT was a valuable tool in assessing spinal cord compression as a result of a postoperative subfascial seroma. Minimally invasive application of a wound catheter can be successfully used to manage this condition. PMID- 27008322 TI - Outcome Following Surgical Correction of Grade 4 Medial Patellar Luxation in Dogs: 47 Stifles (2001-2012). AB - Grade 4/4 medial patellar luxation (MPL) is a complex disease of the canine stifle that often requires surgical realignment of the patella to resolve clinical lameness. Outcome following surgery remains poorly described. Medical records were retrospectively reviewed for surgical correction of grade 4 MPL. Signalment and exam findings, surgical procedures performed, complications, and clinical outcome were reported. Data was statistically analyzed for association with major complication occurrence and unacceptable function following surgery. Forty-seven stifles from 41 dogs were included. The surgical procedures most frequently utilized for patellar realignment were the combination of femoral trochleoplasty, tibial tuberosity transposition, and joint capsule modification. Median in-hospital veterinary examination was performed at 69 days (range 30-179 days) following surgery. Full function was reported for 42.6% of cases (n=20). Acceptable function was reported for 40.4% of cases (n=19). Unacceptable function was reported for 17% of cases (n=8). The overall complication rate was 25.5% (n=12), with revision surgery for major complications required in 12.8% of cases (n=6). Corrective osteotomies were associated with major complications (P < 0.001). In general, pelvic limb function improves following surgical correction of grade 4 MPL; however, a return to full function should be considered guarded. PMID- 27008323 TI - Bilious Vomiting Syndrome in Dogs: Retrospective Study of 20 Cases (2002-2012). AB - Bilious vomiting syndrome (BVS) is a condition historically associated with early morning vomiting of bile, but it is otherwise poorly characterized. The vomiting is thought to result from a reflux of duodenal fluid into the gastric lumen causing mucosal irritation. Medical records from Colorado State University Veterinary Teaching Hospital (CSUVTH) were searched for "canine" and "bilious vomiting syndrome" between 2002 and 2012. Visual inspection confirmed a diagnosis of BVS during the case history. The diagnosis remained BVS for the duration of the dog's contact with the hospital in 17 cases. Therapy involved frequent feedings, late evening meals, gastric acid reducers, prokinetics, and gastroprotectants. Twelve dogs improved with therapy. Five dogs did not improve or were lost to follow-up. The diagnosis of BVS was supplanted in three cases with gastric adenocarcinoma, dietary indiscretion, and hepatopathy. The patient most likely given a diagnosis of BVS would be a young, mixed-breed, castrated male dog with a chronic history of vomiting bile. Response to therapy suggests abnormal gastrointestinal motility, local gastritis, gastric pH, or stimulation of the emetic center may be important factors in BVS. Dogs diagnosed with BVS rarely received a diagnostic evaluation sufficient to qualify it as a diagnosis of exclusion. PMID- 27008324 TI - Use of Cystoscopy to Visualize Morphological Alteration of the Liver in a Posthatchling Turtle ( Cuora trifasciata ). AB - A 55 g, 7 mo old Chinese three-striped box turtle ( Cuora trifasciata ) was presented with a 2 wk history of lethargy and anorexia. The owner attempted various antibiotic treatments without clinical improvement. A cystoscopic evaluation of the coelom was performed. The liver appeared dark red-to-brown presenting multifocal irregularly shaped white-to-tan and roughly round areas of discoloration on the capsular surface. An adult keeled box turtle (Pyxidea mouhotii), which died in the same facility at the same time, had similar hepatic lesions detected upon necropsy. From hepatic lesions, an antibiotic-resistant Escherichia coli was isolated. Antibiotic treatment based on sensitivity testing led to a rapid resolution of the clinical signs in the Cuora trifasciata , with gain of appetite 4 days after the first antibiotic administration. A recheck cystoscopy demonstrated macroscopic resolution of hepatic lesions. This report demonstrates, to the best of the authors' knowledge, for the first time the clinical usefulness of cystoscopy for the diagnostic evaluation of the coelom of small chelonians. This minimally invasive technique is a valuable clinical tool in the medical approach to posthatchling chelonians. PMID- 27008325 TI - Use of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Adrenal Tumors in Dogs. AB - We evaluated the diagnostic accuracy of the contrast-enhanced ultrasonography (CEUS), using a second-generation microbubble contrast agent, in differentiating the different types of adrenal mass lesions in 24 dogs. At B-mode ultrasound, 9 lesions involved the right adrenal gland, 14 the left, and 1 was bilateral. Each dog received a bolus of the contrast agent into the cephalic vein, immediately followed by a 5-mL saline flush. The first contrast enhancement of each adrenal lesion was evaluated qualitatively to assess the degree of enhancement and its distribution during the wash-in and wash-out phases, as well as the presence of non-vascularized areas and specific vascular patterns. Pathological diagnoses were determined in all dogs by histopathology or by cytology. Combining enhancement degree and vascularity resulted in the best predictive model, allowing CEUS to differentiate adrenocortical adenoma (n=10), adenocarcinoma (n=7), and pheochromocytoma (n=7) with an accuracy of 91.7% (P < 0.001). Combining enhancement degree and vascularity, CEUS can discriminate malignant versus benign adrenal lesions with a sensitivity of 100.0%, a specificity of 80.0%, and an accuracy of 91.7% (P < 0.001). In conclusion, results of this study confirm that CEUS is useful for differentiating between the different types of adrenal tumors in dogs. PMID- 27008326 TI - Retrospective Study of 122 Dogs That Were Treated with the Antifibrinolytic Drug Aminocaproic Acid: 2010-2012. AB - Antifibrinolytic drugs are used to promote hemostasis and decrease the need for red blood cell transfusion. Medical records of 122 dogs that were prescribed either oral or intravenous aminocaproic acid between 2010 and 2012 were evaluated retrospectively. Of the 122 dogs, three experienced possible drug-related adverse effects. No significant differences were identified between dogs that experienced adverse effects and those that did not and the possible adverse effects noted were all minor. All dogs that received packed red blood cell transfusions were evaluated for correlations between baseline packed cell volume or dose of red blood cells and aminocaproic acid dose and no correlation was identified. Dogs that received aminocaproic acid as a treatment for active bleeding were divided by cause of hemorrhage into the following groups: neoplastic, non-neoplastic, and unknown. No significant differences in aminocaproic acid dose or the percentage of patients requiring a blood transfusion were identified between groups. PMID- 27008328 TI - Effect of Evolutionary Adaption on Xylosidase Activity in Thermotolerant Yeast Isolates Kluyveromyces marxianus NIRE-K1 and NIRE-K3. AB - Efficient use of xylose along with glucose is necessary for the economic production of lignocellulosic based biofuels. Xylose transporters play an important role in the microorganisms for efficient utilization of xylose. In the present study, a novel method has been developed for a rapid assay of xylose transport activity in the xylose-utilizing isolates and other known yeasts. An assay was conducted to compare the activity of beta-xylosidase using p nitrophenyl-beta-D-xylopyranoside (pNPX) in the intact, intracellular, and extracellular yeasts cells showing xylose transporter. Saccharomyces cerevisiae (MTCC 170) showed no xylosidase activity, while little growth was observed in the xylose-containing medium. Although other yeasts, i.e., Kluyveromyces marxianus NIRE-K1 (MTCC 5933), K. marxianus NIRE-K3 (MTCC 5934), and Candida tropicalis (MTCC 230), showed xylosidase activity in intact, intracellular, and extracellular culture. The xylosidase activity in intact cell was higher than that of extracellular and intracellular activity in all the yeast cells. The enzyme activity was higher in case of K. marxianus NIRE-K1 and K. marxianus NIRE K3 rather than the C. tropicalis. Further, better xylosidase activity was observed in adapted K. marxianus cells which were 2.79-28.46 % higher than that of native (non-adapted) strains, which indicates the significant improvement in xylose transportation. PMID- 27008327 TI - Effects of Host Plant Factors on the Bacterial Communities Associated with Two Whitefly Sibling Species. AB - BACKGROUND: Although discrepancy in the specific traits and ecological characteristics of Bemisia tabaci between species are partially attributed to the B. tabaci-associated bacteria, the factors that affect the diversity of B. tabaci associated bacteria are not well-understood. We used the metagenomic approach to characterize the B. tabaci-associated bacterial community because the approach is an effective tool to identify the bacteria. METHODOLOGY AND RESULTS: To investigate the effects of the host plant and a virus, tomato yellow leaf curl virus (TYLCV), on the bacterial communities of B. tabaci sibling species B and Q, we analyzed the bacterial communities associated with whitefly B and Q collected from healthy cotton, healthy tomato, and TYLCV-infected tomato. The analysis used miseq-based sequencing of a variable region of the bacterial 16S rDNA gene. For the bacteria associated with B. tabaci, we found that the influence of the host plant species was greater than that of the whitefly cryptic species. With further analysis of host plants infected with the TYLCV, the virus had no significant effects on the B. tabaci-associated bacterial community. CONCLUSIONS: The effects of different plant hosts and TYLCV-infection on the diversity of B. tabaci associated bacterial communities were successfully analyzed in this study. To explain why B. tabaci sibling species with different host ranges differ in performance, the analysis of the bacterial community may be essential to the explanation. PMID- 27008329 TI - Response to Transcranial Direct Current Stimulation in a Case of Episodic Obsessive Compulsive Disorder. PMID- 27008330 TI - Ketamine Anesthesia, Efficacy of Electroconvulsive Therapy, and Cognitive Functions in Treatment-Resistant Depression. AB - OBJECTIVES: Electroconvulsive therapy (ECT) is the most effective treatment for drug-resistant depression (DRD). Because a single infusion of ketamine may exert both a rapid antidepressant effect and a quick improvement of cognition, the aim of the present study was to assess whether ketamine, as an anesthetic drug for ECT, can augment the antidepressant activity of the procedure and/or exert a beneficial effect on cognition. METHODS: A total of 11 male and 34 female patients with DRD, aged 21 to 75 years, were included in the study. Fifteen patients (group 1) received only thiopental anesthesia, 15 patients (group 2) had their second and third ECT sessions with ketamine, and 15 patients (group 3) had ketamine for the second, fourth, sixth, eighth, and tenth sessions. Depression intensity was measured by the 17-item Hamilton Depression Rating Scale. Cognitive functions were measured before and after ECT, assessing visual-spatial abilities, verbal auditory memory, working memory, and executive functions. RESULTS: Before the ECT, the mean (SD) intensity of depression was 32 (6) points on the Hamilton Depression Rating Scale and the mean number of ECT sessions was 10.8 (1.5), with no difference between groups. After the last ECT session, the intensity of depression was significantly lower in group 3, compared with group 1. Cognitive assessments after ECT showed a more marked worsening in verbal memory in patients with added ketamine anesthesia. CONCLUSIONS: The addition of ketamine may be connected with better antidepressant efficacy of ECT, compared with only thiopental anesthesia. However, patients with added ketamine had worse results on some of the indices measuring verbal memory. PMID- 27008331 TI - Representations of ECT in English-Language Film and Television in the New Millennium. AB - OBJECTIVE: The aim of the study was to survey the media landscape to determine whether visual depictions of electroconvulsive therapy (ECT) are becoming more or less medically accurate in the new millennium. METHOD: English-language film and television shows depicting ECT were analyzed for patient demographics, administrator roles, indication, consent, anesthesia, paralytics, bite block, lead placement, electroencephalogram, and outcome. RESULTS: Thirty-nine ECT scenes were viewed, and just 3 included all 5 essential tools of modern ECT: anesthesia, paralytic, electrodes, electroencephalogram, and a bite block. CONCLUSIONS: Media depictions of ECT do not reflect current practice. Too often, ECT is portrayed as a torture technique rather than an evidenced-based therapy, and even in a therapeutic setting, it is too often shown with outdated techniques. PMID- 27008333 TI - Polymeric Micelles with Uniform Surface Properties and Tunable Size and Charge: Positive Charges Improve Tumor Accumulation. AB - The influence of surface charge on biodistribution and tumor accumulation remains debatable because most research has been carried out by changing the surface functional groups of nanocarriers. In this work, to avoid the interference of different surface properties such as chemical composition and hydrophilicity, polymeric micelles with uniform PEG coatings and continuously tunable sizes or zeta potentials were developed via a facile route. Therefore, the influence of surface charge on the biological functions of micelles with the same size and surface properties could be well-explored. In this case, positive charge was found to enhance both tumor cellular uptake and tumor accumulation. Immunofluorescence staining indicated that the improved tumor accumulation was mainly due to the tumor vasculature targeting of positively charged micelles. It is predicted that efficient drug delivery systems for both tumor vasculature and cancer cell targeting can be realized based on positively charged micelles. PMID- 27008332 TI - Kat3 coactivators in somatic stem cells and cancer stem cells: biological roles, evolution, and pharmacologic manipulation. AB - Long-lived somatic stem cells regenerate adult tissues throughout our lifetime. However, with aging, there is a significant deterioration in the function of stem and progenitor cells, which contribute to diseases of aging. The decision for a long-lived somatic stem cell to become activated and subsequently to undergo either a symmetric or an asymmetric division is a critical cellular decision process. The decision to preferentially divide symmetrically or asymmetrically may be the major fundamental intrinsic difference between normal somatic stem cells and cancer stem cells. Based upon work done primarily in our laboratory over the past 15 years, this article provides a perspective on the critical role of somatic stem cells in aging. In particular, we discuss the importance of symmetric versus asymmetric divisions in somatic stem cells and the role of the differential usage of the highly similar Kat3 coactivators, CREB-binding protein (CBP) and p300, in stem cells. We describe and propose a more complete model for the biological mechanism and roles of these two coactivators, their evolution, and unique roles and importance in stem cell biology. Finally, we discuss the potential to pharmacologically manipulate Kat3 coactivator interactions in endogenous stem cells (both normal and cancer stem cells) to potentially ameliorate the aging process and common diseases of aging. PMID- 27008334 TI - Effect of Perflubron-induced lung growth on pulmonary vascular remodeling in congenital diaphragmatic hernia. AB - PURPOSE: Congenital diaphragmatic hernia (CDH) involves lung hypoplasia and pulmonary hypertension (PH). Post-natal Perflubron ventilation induces lung growth. This phenomenon is called Perflubon-induced lung growth (PILG). However, it does not appear to ameliorate PH in CDH. We aim to determine the effect of PILG on pulmonary vascular remodeling in neonates with CDH and PH requiring extracorporeal membrane oxygenation (ECMO). METHODS: Lung tissue from four patients was obtained, three treated with PILG + ECMO, and one maintained on conventional ventilation + ECMO (control). The distribution of collagen was assessed with Masson's trichrome stain. Immunohistochemistry was done to assess cell proliferation and immunofluorescence to assess vascular morphology. RESULTS: Comparing PILG vs. control, there was an increase in vessel wall diameter (6.85 MUm, 10.28 MUm, and 10.35 MUm vs. 4.34 MUm), increase in collagen thickness in two PILG patients (35.66 MUm, 14.23 MUm, and 38.46 MUm vs. 22.16 MUm), and decrease in lumen diameter despite similar total area (48.99 MUm, 41.74 MUm, and 36.32 MUm vs. 51.56 MUm) for each PILG patient vs. the control patient, respectively. CONCLUSION: PILG does not appear to improve pulmonary vascular remodeling that occurs with PH. The findings are descriptive and will require larger samples to validate the significance of the findings. Overall, further studies will be required to identify the mechanistic causes of PH in CDH to create effective treatments. PMID- 27008335 TI - Modified iliac screw fixation: technique and clinical application. AB - BACKGROUND: A conventional iliac bolt and the S2 alar iliac screw fixation technique (S2AI) are commonly used sacropelvic fixation techniques. However, conventional iliac bolt technique requires a lateral connector and commonly has prominent screw head problems. S2AI reportedly has a high instrument failure rate. We aim to introduce a modified iliac screw fixation technique and to investigate its clinical application in adult patients. METHODS: The entrance site of the modified iliac screw fixation technique was 1 cm medial and 1 cm caudal from the posterosuperior iliac spine. From 2009 to 2015, ten adult patients underwent sacropelvic fixation with the modified iliac screw fixation technique in our spine clinic. A minimum 12-month clinical and radiographic follow-up was adopted. The mean follow-up period was 30.7 months (12-74 months). Mean number of fixation levels was 7.7 segments (5-10 segments). RESULTS: Postoperatively, the C7 plumb line (SVA) was significantly decreased (P = 0.04). Upon the last X-ray, SVA did not differ between postoperative and the last X-ray (P = 0.1). There was no breakage during our follow-up period. There was no prominent screw head. There were no cases requiring implant removal. CONCLUSIONS: The modified iliac screw fixation technique does not cause prominence in the sacral region, and does not require a lateral connector, both of which are necessary when using the classical iliac bolt technique. This technique also avoids the acute angle between the screw head and the shaft of the screw commonly seen in S2AI. The modified iliac screw fixation technique can be an effective alternative for sacropelvic fixation. PMID- 27008336 TI - Medical student perceptions of research and research-orientated careers: An international questionnaire study. AB - BACKGROUND: Engaging and inspiring the next generation of physician-scientists at an early stage is recognised as key to ensure the future of medical research. However, little is known about medical student perceptions of research. OBJECTIVES: We attempted to ascertain perceptions of research and research orientated careers from medical students studying in different countries. METHODS: An online questionnaire was developed, piloted, and promoted to medical students in various countries. RESULTS: 1625 responses were collected from 38 countries. Analysis was restricted to data collected from countries with >100 responses (n = 890). Less than half the respondents felt their medical school provided adequate research training. Key perceived barriers to research participation as a student included lack of time and difficulty finding mentors or projects. A significant gender disparity existed in research ambitions of students with females desiring less research involvement. The importance of barriers and satisfaction with research training differed significantly between countries. CONCLUSIONS: Students perceive a number of key barriers to research involvement and pursuit of research-orientated careers. Programmes designed to engage students with research should focus on overcoming identified barriers. Greater effort is needed to engage female students who report more significant barriers and less desire to follow research-orientated careers. PMID- 27008337 TI - [Geriatric Pharmacotherapy in Urology: An Introduction from a Geriatric Pharmacist's Perspective]. AB - In Germany, too, adverse drug events (ADEs) have been identified as a central problem in the care of geriatric patients. Especially in elderly patients with multimorbidity and increasing frailty, ADEs are among the most frequent and cost intensive causes of illness in healthcare. In most cases, they are due to drug related diseases, which necessitate enhanced risk awareness and improved cooperation between physicians, medical specialists, geriatric nurses and pharmacists. In this context, the use of urologic medication for geriatric patients requires particular attention by the consultant. PMID- 27008338 TI - Thymidylate Limitation Potentiates Cephalosporin Activity toward Enterococci via an Exopolysaccharide-Based Mechanism. AB - Multidrug resistant enterococci are major causes of nosocomial infections. Prior therapy with cephalosporins increases the risk of developing an enterococcal infection due to the intrinsic resistance of enterococci to these antibiotics. While progress has been made toward understanding the genetic and biochemical mechanisms of cephalosporin resistance, available data indicate that as-yet unidentified resistance factors must exist. Here, we describe results of a screen to identify small molecules capable of sensitizing enterococci to broad-spectrum cephalosporins. We found that both Enterococcus faecalis and Enterococcus faecium were sensitized to broad and expanded-spectrum cephalosporins when thymidylate production was impaired, whether by direct inhibition of thymidylate synthase, or by limiting production of cofactors required for its activity. Cephalosporin potentiation is the result of altered exopolysaccharide production due to reduced dTDP-glucose synthesis. Hence, exopolysaccharide production is a previously undescribed contributor to the intrinsic cephalosporin resistance of enterococci and serves as a new target for antienterococcal therapeutics. PMID- 27008339 TI - Polydimethylsiloxane (PDMS) modulates CD38 expression, absorbs retinoic acid and may perturb retinoid signalling. AB - Polydimethylsiloxane (PDMS) is the most commonly used material in the manufacture of customized cell culture devices. While there is concern that uncured PDMS oligomers may leach into culture medium and/or hydrophobic molecules may be absorbed into PDMS structures, there is no consensus on how or if PDMS influences cell behaviour. We observed that human umbilical cord blood (CB)-derived CD34(+) cells expanded in standard culture medium on PDMS exhibit reduced CD38 surface expression, relative to cells cultured on tissue culture polystyrene (TCP). All trans retinoic acid (ATRA) induces CD38 expression, and we reasoned that this hydrophobic molecule might be absorbed by PDMS. Through a series of experiments we demonstrated that ATRA-mediated CD38 expression was attenuated when cultures were maintained on PDMS. Medium pre-incubated on PDMS for extended durations resulted in a time-dependant reduction of ATRA in the medium and increasingly attenuated CD38 expression. This indicated a time-dependent absorption of ATRA into the PDMS. To better understand how PDMS might generally influence cell behaviour, Ingenuity Pathway Analysis (IPA) was used to identify potential upstream regulators. This analysis was performed for differentially expressed genes in primary cells including CD34(+) haematopoietic progenitor cells, mesenchymal stromal cells (MSC), and keratinocytes, and cell lines including prostate cancer epithelial cells (LNCaP), breast cancer epithelial cells (MCF-7), and myeloid leukaemia cells (KG1a). IPA predicted that the most likely common upstream regulator of perturbed pathways was ATRA. We demonstrate here that ATRA is absorbed by PDMS in a time-dependent manner and results in the concomitant reduced expression of CD38 on the cell surface of CB-derived CD34(+) cells. PMID- 27008340 TI - The Value of Information in Decision-Analytic Modeling for Malaria Vector Control in East Africa. AB - Decision analysis tools and mathematical modeling are increasingly emphasized in malaria control programs worldwide to improve resource allocation and address ongoing challenges with sustainability. However, such tools require substantial scientific evidence, which is costly to acquire. The value of information (VOI) has been proposed as a metric for gauging the value of reduced model uncertainty. We apply this concept to an evidenced-based Malaria Decision Analysis Support Tool (MDAST) designed for application in East Africa. In developing MDAST, substantial gaps in the scientific evidence base were identified regarding insecticide resistance in malaria vector control and the effectiveness of alternative mosquito control approaches, including larviciding. We identify four entomological parameters in the model (two for insecticide resistance and two for larviciding) that involve high levels of uncertainty and to which outputs in MDAST are sensitive. We estimate and compare a VOI for combinations of these parameters in evaluating three policy alternatives relative to a status quo policy. We find having perfect information on the uncertain parameters could improve program net benefits by up to 5-21%, with the highest VOI associated with jointly eliminating uncertainty about reproductive speed of malaria-transmitting mosquitoes and initial efficacy of larviciding at reducing the emergence of new adult mosquitoes. Future research on parameter uncertainty in decision analysis of malaria control policy should investigate the VOI with respect to other aspects of malaria transmission (such as antimalarial resistance), the costs of reducing uncertainty in these parameters, and the extent to which imperfect information about these parameters can improve payoffs. PMID- 27008341 TI - Whole genome and exome sequencing realignment supports the assignment of KCNJ12, KCNJ17, and KCNJ18 paralogous genes in thyrotoxic periodic paralysis locus: functional characterization of two polymorphic Kir2.6 isoforms. AB - Next-generation sequencing (NGS) has enriched the understanding of the human genome. However, homologous or repetitive sequences shared among genes frequently produce dubious alignments and can puzzle NGS mutation analysis, especially for paralogous potassium channels. Potassium inward rectifier (Kir) channels are important to establish the resting membrane potential and regulating the muscle excitability. Mutations in Kir channels cause disorders affecting the heart and skeletal muscle, such as arrhythmia and periodic paralysis. Recently, a susceptibility muscle channelopathy-thyrotoxic periodic paralysis (TPP)-has been related to Kir2.6 channel (KCNJ18 gene). Due to their high nucleotide sequence homology, variants found in the potassium channels Kir2.6 and Kir2.5 have been mistakenly attributable to Kir2.2 polymorphisms or mutations. We aimed at elucidating nucleotide misalignments by performing realignment of whole exome sequencing (WES) and whole genome sequencing (WGS) reads to specific Kir2.2, Kir2.5, and Kir2.6 cDNA sequences using BWA-MEM/GATK pipeline. WES/WGS reads correctly aligned 26.9/43.2, 37.6/31.0, and 35.4/25.8 % to Kir2.2, Kir2.5, and Kir2.6, respectively. Realignment was able to reduce over 94 % of misalignments. No putative mutations of Kir2.6 were identified for the three TPP patients included in the cohort of 36 healthy controls using either WES or WGS. We also distinguished sequences for a single Kir2.2, a single Kir2.5 sequence, and two Kir2.6 isoforms, which haplotypes were named RRAI and QHEV, based on changes at 39, 40, 56, and 249 residues. Electrophysiology records on both Kir2.6_RRAI and _QHEV showed typical rectifying currents. In our study, the reduction of misalignments allowed the elucidation of paralogous gene sequences and two distinct Kir2.6 haplotypes, and pointed the need for checking the frequency of these polymorphisms in other populations with different genetic background. PMID- 27008342 TI - Resonance energy transfer and competing processes in donor-acceptor of sodium zinc (II)-2,9,16,23-phthalocyanine tetracarboxylate molecule. AB - An important issue that should be taken into consideration when applying the molecules in photodynamic therapy (PDT) of cancer is the occurrence of homo resonance energy transfer process between them. We have determined the probability of energy transfer for sodium zinc (II)-2,9,16,23-phthalocyanine tetracarboxylate (ZnPc(COONa)4) molecules in aqueous NaOH solution. The homo quenching effect of the molecule was also measured by calculating the diffusion controlled bimolecular rate constant of k q = 6.5 * 10(9) M(-1)s(-1), which did not show a significant competition with the rate constant of homo-resonance energy transfer process at the applied concentration of the molecules (6 MUM). The Forster radius (R 0) for ZnPc(COONa)4 molecules was calculated to be 42 A. The availability of these calculations should facilitate the potential application of ZnPc(COONa)4 molecule as an anticancer drug in PDT. PMID- 27008344 TI - Efficacy of Cinnamaldehyde Against Enteric Viruses and Its Activity After Incorporation Into Biodegradable Multilayer Systems of Interest in Food Packaging. AB - Cinnamaldehyde (CNMA), an organic compound that gives cinnamon its flavor and odor, was investigated for its virucidal activity on norovirus surrogates, murine norovirus (MNV) and feline calicivirus (FCV), and hepatitis A virus (HAV). Initially, different concentrations of CNMA (0.1, 0.5 and 1 %) were individually mixed with each virus at titers of ca. 6-7 log10 TCID50/ml and incubated 2 h at 4 and 37 degrees C. CNMA was effective in reducing the titers of norovirus surrogates in a dose-dependent manner after 2 h at 37 degrees C, while HAV titers were reduced by 1 log10 after treatment with 1 % of CNMA. When incubation time was extended, HAV titers were reduced by 3.4 and 2.7 log10 after overnight incubation at 37 degrees C with 1 and 0.5 % of CNMA, respectively. Moreover, this paper analyzed, for the first time, the antiviral activity of adding an active electrospun interlayer based on zein and CNMA to a polyhydroxybutyrate packaging material (PHB) in a multilayer form. Biodegradable multilayer systems prepared with 2.60 mg/cm(2) (~9.7 %) of CNMA completely inactivated FCV according to ISO 22196:2011, while MNV titers were reduced by 2.75 log10. When the developed multilayer films were evaluated after one month of preparation or at 25 degrees C, the antiviral activity was reduced as compared to freshly prepared multilayer films evaluated at 37 degrees C. The results show the excellent potential of this system for food contact applications as well as for active packaging technologies in order to maintain or extend food quality and safety. PMID- 27008345 TI - Retrospective analysis of anterior skull base CSF leaks and endoscopic repairs at Leeds. AB - OBJECTIVES: Over the past 10 years, endoscopic endonasal anterior skull base surgery has become established practice. Surgeons carrying out this surgery need to be able to endoscopically repair primary and secondary CSF leaks. A growing number of techniques have been adopted to date. This article highlights one UK institution's experience in the management of anterior skull base leaks, and how surgeons there have identified leak defect types that are difficult to seal and how they have adopted a new way of repairing them, which uses a fat ring. METHODS: Seventy-six patients requiring CSF leak repairs were identified form a prospective data base of 240 endoscopic anterior skull base procedures at the General Infirmary at Leeds performed between July 2009 and October 2015. RESULTS: Fifty-one cases have undergone an endoscopic primary repair of a skull base defect following resection of a lesion and, of these, 10 (19%) cases required a secondary repair. This was particularly over the planum sphenoidale area. Twenty five cases had undergone an endoscopic repair as the primary procedure. This was due to a spontaneous leak in 7 cases, trauma in 3 cases, following craniotomy in 3 cases and following pituitary surgery in 2 cases. The remaining 10 were the secondary repairs referred to above. CONCLUSIONS: A number of techniques are effective in CSF repair. Defects over the planum sphenoidale and clivus are associated with the highest recurrence, requiring specific repair techniques. Utilisation of a 5 "F" repair helps to prevent recurrence in high risk defect cases over the optic chiasm. The 5 "F" repair used takes the form of placing intradural Fat and Fascia; next a Fat sealing ring is used, followed by a nasoseptal Flap; finally a supporting fragmentable pack is applied. PMID- 27008346 TI - A homogenized constrained mixture (and mechanical analog) model for growth and remodeling of soft tissue. AB - Most mathematical models of the growth and remodeling of load-bearing soft tissues are based on one of two major approaches: a kinematic theory that specifies an evolution equation for the stress-free configuration of the tissue as a whole or a constrained mixture theory that specifies rates of mass production and removal of individual constituents within stressed configurations. The former is popular because of its conceptual simplicity, but relies largely on heuristic definitions of growth; the latter is based on biologically motivated micromechanical models, but suffers from higher computational costs due to the need to track all past configurations. In this paper, we present a temporally homogenized constrained mixture model that combines advantages of both classical approaches, namely a biologically motivated micromechanical foundation, a simple computational implementation, and low computational cost. As illustrative examples, we show that this approach describes well both cell-mediated remodeling of tissue equivalents in vitro and the growth and remodeling of aneurysms in vivo. We also show that this homogenized constrained mixture model suggests an intimate relationship between models of growth and remodeling and viscoelasticity. That is, important aspects of tissue adaptation can be understood in terms of a simple mechanical analog model, a Maxwell fluid (i.e., spring and dashpot in series) in parallel with a "motor element" that represents cell-mediated mechanoregulation of extracellular matrix. This analogy allows a simple implementation of homogenized constrained mixture models within commercially available simulation codes by exploiting available models of viscoelasticity. PMID- 27008347 TI - Heterostructured WS2 /CH3 NH3 PbI3 Photoconductors with Suppressed Dark Current and Enhanced Photodetectivity. AB - Heterostructured photoconductors based on hybrid perovskites and 2D transition metal dichalcogenides are fabricated and characterized. Due to the superior properties of CH3 NH3 PbI3 and WS2 , as well as the efficient interfacial charge transfer, such photoconductors show high performance with on/off ratio of ~10(5) and responsivity of ~17 A W(-1) . Furthermore, the response times of the heterostructured photoconductors are four orders of magnitude faster compared to the counterpart of a perovskite single layer. PMID- 27008348 TI - Use of the Xbox Kinect virtual gaming system to improve gait, postural control and cognitive awareness in an individual with Progressive Supranuclear Palsy. AB - PURPOSE: The purpose of this report is to describe an intervention using the Xbox Kinect virtual gaming system to improve gait, postural control and cognitive awareness in order to reduce falls and improve the quality of life for an individual with Progressive Supranuclear Palsy. METHODS: A 65-year-old woman with a five-year history of PSP and frequent falls presented for physical therapy. Her case was complicated by poor ability to visually track objects, axial rigidity, retropulsion, poor postural control with reaching and declines in cognitive awareness. Intervention was provided using the Xbox Kinect for 12 one-hour sessions over six weeks in an outpatient setting. Games were selected to challenge functional motor and cognitive tasks based on patient enjoyment. RESULTS: The Xbox Kinect intervention may have contributed to a decline in falls and maintenance of scores on the BBS, TUG and 10 Meter Walk Tests above fall risk values. A decline in quality of life measures, PDQ-39 and FFABQ, may be attributed to an increase in cognitive awareness of deficits promoted by the intervention structure. CONCLUSION: Implementation of a gaming intervention using the Xbox Kinect is feasible for reducing fall risk, maintaining function and improving cognitive awareness when used in an outpatient setting. Implications for Rehabilitation Progressive Supranuclear Palsy is a rare and rapidly progressive neurodegenerative disease wherethere is a lack of long-term rehabilitation options to help slow their rapid progressions. Our case demonstrates the feasibility of an intervention using a virtual gaming system to helpmaintain functional mobility, balance and independence for an individual with PSP. Collaborative interactions between game companies and physical therapists will improve theability of virtual games to address rehabilitation goals within neurodegenerative populations. PMID- 27008349 TI - Robust breathing signal extraction from cone beam CT projections based on adaptive and global optimization techniques. AB - We present a study of extracting respiratory signals from cone beam computed tomography (CBCT) projections within the framework of the Amsterdam Shroud (AS) technique. Acquired prior to the radiotherapy treatment, CBCT projections were preprocessed for contrast enhancement by converting the original intensity images to attenuation images with which the AS image was created. An adaptive robust z normalization filtering was applied to further augment the weak oscillating structures locally. From the enhanced AS image, the respiratory signal was extracted using a two-step optimization approach to effectively reveal the large scale regularity of the breathing signals. CBCT projection images from five patients acquired with the Varian Onboard Imager on the Clinac iX System Linear Accelerator (Varian Medical Systems, Palo Alto, CA) were employed to assess the proposed technique. Stable breathing signals can be reliably extracted using the proposed algorithm. Reference waveforms obtained using an air bellows belt (Philips Medical Systems, Cleveland, OH) were exported and compared to those with the AS based signals. The average errors for the enrolled patients between the estimated breath per minute (bpm) and the reference waveform bpm can be as low as -0.07 with the standard deviation 1.58. The new algorithm outperformed the original AS technique for all patients by 8.5% to 30%. The impact of gantry rotation on the breathing signal was assessed with data acquired with a Quasar phantom (Modus Medical Devices Inc., London, Canada) and found to be minimal on the signal frequency. The new technique developed in this work will provide a practical solution to rendering markerless breathing signal using the CBCT projections for thoracic and abdominal patients. PMID- 27008350 TI - Potassium 4,4'-Bis(dinitromethyl)-3,3'-azofurazanate: A Highly Energetic 3D Metal Organic Framework as a Promising Primary Explosive. AB - Environmentally acceptable alternatives to toxic lead-based primary explosives are becoming increasingly important for energetic materials. In this study, potassium 4,4'-bis(dinitromethyl)-3,3'-azofurazanate, comprising two dinitromethyl groups and an azofurazan moiety, was synthesized and isolated as a new energetic 3D metal-organic framework (MOF). Several attractive properties, including a density of 2.039 g cm(-3) , a decomposition temperature of 229 degrees C, a detonation velocity of 8138 m s(-1) , a detonation pressure of 30.1 GPa, an impact sensitivity of 2 J, and friction sensitivity of 20 N make 4 a good candidate as a green primary explosive. PMID- 27008351 TI - Editorial retraction. PMID- 27008353 TI - Ready for a Revolution in Contact Lenses? PMID- 27008352 TI - Correction: Engineered Promoters for Potent Transient Overexpression. PMID- 27008354 TI - Revolutionary Future Uses of Contact Lenses. PMID- 27008356 TI - Error in Table. PMID- 27008357 TI - Creating the Medical Schools of the Future. AB - Despite wide consensus on needed changes in medical education, experts agree that the gap continues to widen between how physicians are trained and the future needs of our health care system. A new model for medical education is needed to create the medical school of the future. The American Medical Association (AMA) is working to support innovative models through partnerships with medical schools, educators, professional organizations, and accreditors. In 2013, the AMA designed an initiative to support rapid innovation among medical schools and disseminate the ideas being tested to additional medical schools. Awards of $1 million were made to 11 medical schools to redesign curricula for flexible, individualized learning pathways, measure achievement of competencies, develop new assessment tools to test readiness for residency, and implement new models for clinical experiences within health care systems. The medical schools have partnered with the AMA to create the AMA Accelerating Change in Medical Education Consortium, working together to share prototypes and participate in a national evaluation plan. Most of the schools have embarked on major curriculum revisions, replacing as much as 25% of the curriculum with new content in health care delivery and health system science in all four years of training. Schools are developing new certification in quality and patient safety and population management. In 2015, the AMA invited 21 additional schools to join the 11 founding schools in testing and disseminating innovation through the consortium and beyond. PMID- 27008358 TI - Where Do Soldiers Really Come From? A Faculty Development Workshop on Veteran Centered Care. AB - PROBLEM: Addressing the medical concerns of veterans in both civilian health care systems and the Veterans Affairs (VA) health care system, where staff are familiar with issues of military reintegration, remains difficult but is increasingly important. APPROACH: In 2013, the authors developed and implemented a faculty development workshop for practicing clinicians using the documentary Where Soldiers Come From. The workshop included topics on unconscious bias, the service member trajectory, health care disparities, and strategies for overcoming barriers to treating veterans with posttraumatic stress disorder and traumatic brain injury. The workshop engaged faculty in the following active-learning techniques: images in education; trigger video; critical thinking and reflective writing; think-pair-share; and large-group discussion. The workshop has been conducted at three locations with 46 health care professionals. OUTCOMES: Thirty one of 37 (84%) participants who completed the workshop evaluation were VA employees. The evaluation results show 25/32 (78.1%) participants indicated the workshop activities changed their knowledge, attitudes, and/or skills; 22/34 (64.7%) stated they had a better understanding of how to develop a care plan for veterans; and 27/34 (79.4%) stated they gained a better understanding of how to prepare for issues around returning veterans. NEXT STEPS: To address the issue of veteran-centered care education more broadly, the authors have developed a massive open online course for health professionals, using most of the content from this workshop, which will be offered in spring 2016. Another important next step will be to deliver this workshop to and collect evaluation data from non-VA providers. PMID- 27008359 TI - Interprofessional Care Conferences for High-Risk Primary Care Patients. AB - PROBLEM: As health care systems convert to team-based care, the need to improve interprofessional education is tremendous. In addition to formal instruction, trainees need authentic team-based workplace learning experiences. APPROACH: The authors designed the PACT-ICU (Patient-Aligned Care Team Interprofessional Care Update) conference to provide team-based care to high-risk patients while teaching trainees principles of interprofessionalism and modeling relevant behaviors. Trainees, supervisors, and affiliated support staff from the fields of internal medicine, nurse practitioner, pharmacy, psychology, and nursing all participate in this conference. During the conference, each participant focuses on the narrative of the patient's illness from his/her own professional perspective. A multifaceted care plan with specific action items is the product of the conference. To evaluate this workplace learning opportunity, the authors recorded patient characteristics, plus trainees' participation and satisfaction. OUTCOMES: Over the first 16 months (2013-2014) of the PACT-ICU, 33 trainees presented 79 patients. Each trainee presented two or three times each academic year. Patients were 90% male; their mean age was 64.5 years (SD 9.3, range 28 92), and their mean calculated 90-day risk of death or hospitalization was 22% (SD 14%, range 1%-45%).Overall, all surveyed trainees (n = 32; 97% response rate) expressed satisfaction, reporting that the conference was "helpful" or "very helpful" in developing treatment plans. NEXT STEPS: Further assessment of change in trainee behavior related to interprofessional team care, patient-level outcomes (e.g., quality of care and utilization), and factors facilitating dissemination of the model to other academic clinic settings is necessary. PMID- 27008360 TI - Changing Physician Behavior With Implementation Intentions: Closing the Gap Between Intentions and Actions. AB - In medical education, even well-intentioned learners struggle to change their practice. This intention-action gap is a well-described phenomenon. Strong commitment to changing behaviors is important, but by itself it is only a modest predictor of goal attainment.Implementation intentions are an extensively studied strategy from cognitive psychology that have been shown to close the intention action gap and increase goal attainment across myriad domains. Implementation intentions are "if-then" plans that specify an anticipated future situation and a planned response-"If I encounter situation X, then I will respond with action Y." They differ from simple goals, which specify only a desired behavior or outcome "I intend to perform action Z." Despite this subtle difference, they have shown substantial effectiveness over goals alone in increasing goal attainment.In this article, the authors first describe implementation intentions, review the substantial body of evidence demonstrating their effectiveness, and explain the underlying psychological mechanisms. They then illustrate the connections between implementation intentions and established learning theory. The final section focuses on forming effective implementation intentions in medical education. The authors provide concrete examples across the continuum of learners (from medical students to attending physicians) and competencies, and make recommendations for when and how to employ implementation intentions. PMID- 27008361 TI - Academic Medicine's Critical Role in the "Third Curve" of Health Care. AB - Over the last several years, the health care landscape has changed at an unprecedented rate due to new economic and regulatory forces ushered in by the Affordable Care Act and the introduction of innovative technologies, such as personalized medicine, that are poised to open the door to consumer-driven health care. Tremendous pressure exists on academic health centers to rapidly evolve clinically while not abandoning their unique academic mission. The convergence of personalized medicine, new digital technologies, and changes in health professionals' scope of practice alongside new payment structures will accelerate the move to a patient-centered health system. In this Commentary, the author argues that these new tools and resources must be embraced to improve the health of patients. With the traditional, fee-for-service model of care as "Curve I" and the post-Flexner era of population-based medicine as "Curve II," the author identifies the emergence of "Curve III," which is characterized by patient centered, consumer-directed models of care. As the old models of health care undergo transition and the impact of technology and analytics grow, future practitioners must be trained to embrace this change and function effectively in the "third curve" of consumer-driven health care. PMID- 27008362 TI - Gaussian mixture models based 2D-3D registration of bone shapes for orthopedic surgery planning. AB - In orthopedic surgery, precise kinematics assessment helps the diagnosis and the planning of the intervention. The correct placement of the prosthetic component in the case of knee replacement is necessary to ensure a correct load distribution and to avoid revision of the implant. 3D reconstruction of the knee kinematics under weight-bearing conditions becomes fundamental to understand existing in vivo loads and improve the joint motion tracking. Existing methods rely on the semiautomatic positioning of a shape previously segmented from a CT or MRI on a sequence of fluoroscopic images acquired during knee flexion. We propose a method based on statistical shape models (SSM) automatically superimposed on a sequence of fluoroscopic datasets. Our method is based on Gaussian mixture models, and the core of the algorithm is the maximization of the likelihood of the association between the projected silhouette and the extracted contour from the fluoroscopy image. We evaluated the algorithm using digitally reconstructed radiographies of both healthy and diseased subjects, with a CT extracted shape and a SSM as the 3D model. In vivo tests were done with fluoroscopically acquired images and subject-specific CT shapes. The results obtained are in line with the literature, but the computational time is substantially reduced. PMID- 27008363 TI - Step characteristic interaction and asymmetry during the approach phase in long jump. AB - The aim of this study was to investigate the relative influence of step length (SL) and step frequency (SF) on step velocity (SV) during the approach run of high-level long jumpers and to quantify the asymmetry of these step characteristics. Spatiotemporal data of the approach run were collected during national competition from 10 long jumpers (age 26.2 +/- 4.1 years, height 1.84 +/ 0.06 m, mass 72.77 +/- 3.23 kg, personal best performance 7.96 +/- 0.30 m). Analyses were conducted for total approach, early approach and late approach. For the total approach 4/10 athletes were SF reliant and 6/10 athletes favoured neither characteristic. At the early approach, 3/10 athletes were SF reliant and 7/10 athletes favoured neither. During late approach 2/10 athletes demonstrated SL reliance, 7/10 athletes were SF reliant and 1/10 athletes favoured neither. Four athletes displayed significant asymmetry for SL and three for SF. However, no athletes demonstrated significant asymmetry for SV indicating that the asymmetrical demands of take-off do not have a marked influence on step characteristic asymmetry, probably due to the constraints of the event. Consideration should be given to the potentially conflicting demands between limbs for individual athletes. PMID- 27008364 TI - A Phylogenetic Comparative Study of Bantu Kinship Terminology Finds Limited Support for Its Co-Evolution with Social Organisation. AB - The classification of kin into structured groups is a diverse phenomenon which is ubiquitous in human culture. For populations which are organized into large agropastoral groupings of sedentary residence but not governed within the context of a centralised state, such as our study sample of 83 historical Bantu-speaking groups of sub-Saharan Africa, cultural kinship norms guide all aspects of everyday life and social organization. Such rules operate in part through the use of differing terminological referential systems of familial organization. Although the cross-cultural study of kinship terminology was foundational in Anthropology, few modern studies have made use of statistical advances to further our sparse understanding of the structuring and diversification of terminological systems of kinship over time. In this study we use Bayesian Markov Chain Monte Carlo methods of phylogenetic comparison to investigate the evolution of Bantu kinship terminology and reconstruct the ancestral state and diversification of cousin terminology in this family of sub-Saharan ethnolinguistic groups. Using a phylogenetic tree of Bantu languages, we then test the prominent hypothesis that structured variation in systems of cousin terminology has co-evolved alongside adaptive change in patterns of descent organization, as well as rules of residence. We find limited support for this hypothesis, and argue that the shaping of systems of kinship terminology is a multifactorial process, concluding with possible avenues of future research. PMID- 27008365 TI - Klinefelter syndrome in preschool children: the importance of an early multidisciplinary approach for patients and families. AB - BACKGROUND: The aim of this study is twofold: to present a multi-disciplinary and multi- centric approach in the early care of patients with Klinefelter Syndrome (KS) and their families and to increase the knowledge about the behavioural phenotype of preschool boys with KS. METHODS: Fifteen boys (mean age 2 years and 7 months) who had been diagnosed prenatally were evaluated in the areas of adaptive skills, developmental level, language, and behaviour. Besides offering information about their child, both parents of each couple were asked to describe their feelings at the time of the prenatal diagnosis and at the time of the study. RESULTS: The behavioural phenotype of the boys of our sample was characterized by a mean Developmental Quotient of 95 (in the normal range) but by low scores in the domain of communication, particularly in the area of expressive language. Behavioural problems were observed in some of the children, and the parents reported significant levels of distress related to their relationship with the child. All parents recalled to have felt very anxious when the diagnosis was given, but 9 of them (75%) said their concern diminished after receiving genetic counseling. CONCLUSIONS: a multi-disciplinary model is essential in the care of 47, XXY boys and in the assistance to their families, in order both to facilitate the children's growth and offer to the parents updated clinical and psychosocial information about the Klinefelter Syndrome and support. PMID- 27008366 TI - Bartonella henselae in Italy: a rare seasonal infection. AB - BACKGROUND: Symptomatic Bartonella henselae infection is considered rare in Europe. Cat fleas transmit the microorganism between cats, but their role in transmission of B. henselae to humans has not been defined. The aim of our study was to perform a retrospective study of detected cases at our Hospital. METHODS: We retrospectively analyzed data of all children showing lymphoadenopathy and a 4 fold increase in specific IgM for B.henselae over the period from June 2010 to May 2015. We therefore examined clinical data, laboratory exams in order to achieve a description of the expression of Bartonella infection in our series: age, geographical area of origin, symptoms, laboratory exams, the seat of the swelling lymph nodes with ultrasound description, and data on biopsy of lymph node when performed. RESULTS: We could identify a total of 7 patients (4 females, range of age: mean age 8.75+/-2.87 SD): 3 cases in 2011 and 1 case per year in 2010, 2012, 2013 and 2014 with an average distance between one case and the sequent of 246.16+/-214.54 days. All patients came from small towns with no preference between the inland and coastal areas. The infection was characterized only by lymphadenopathy with nonspecific alterations at blood tests and with no history of cat scratch. CONCLUSIONS: By our experience, Bartonella infection presents as a seasonal disease with increased incidence in autumn, with peaks in October, and a decrease after spring. In conclusion, infection with Bartonella henselae is an issue to keep in consideration in all cases of lymphadenopathy, especially in children coming from small towns even without a declared cat scratch. PMID- 27008367 TI - [Renal and ureteral injuries. Diagnosis and treatment]. AB - BACKGROUND: In severely injured patients, urologic trauma is diagnosed in about 10 % of patients. Renal trauma is most common, while ureteral trauma is in the majority of cases iatrogenic. These two urologic injuries influence the clinical course, morbidity, and mortality. Thus, rapid identification, sufficient diagnostic workup, and adequate therapy of renal and ureteral injuries are essential. THEME: This article reviews the actual diagnostic procedures, classification, and stage-dependent therapy options in renal and ureteral injuries. PMID- 27008368 TI - Crystal Structure, Electronic Structure, and Photocatalytic Activity of Oxysulfides: La2Ta2ZrS2O8, La2Ta2TiS2O8, and La2Nb2TiS2O8. AB - The novel oxysulfides La2Ta2ZrS2O8 (LTZSO), La2Ta2TiS2O8 (LTTSO), and La2Nb2TiS2O8 (LNTSO) were synthesized, and their crystal structures, electronic structures, and photocatalytic activities for water splitting under visible light were investigated. Density functional theory calculations showed that these compounds are direct-band-gap semiconductors. Close to the conduction band minimum, the main contribution to the band structure comes from the d orbitals of Zr or Ti ions, while the region near the valence band maximum is associated with the 3p orbitals of S ions. The absorption-edge wavelength was determined to be 540 nm for LTZSO and 700 nm for LTTSO and LNTSO. An analysis of the crystal structure using synchrotron X-ray diffraction revealed that these compounds contained antisite defects at transition metal ion sites, and these were considered to be the origin of the broad absorption at wavelengths longer than that corresponding to band-gap excitation. LTZSO was revealed to be active in the oxygen evolution reaction from aqueous solution containing a sacrificial electron acceptor under visible-light illumination. This result was supported by the band alignment and flat-band potential determined by photoelectron spectroscopy and Mott-Schottky plots. PMID- 27008369 TI - Clinical relevance of the effects of reach-to-grasp training using trunk restraint in individuals with hemiparesis poststroke: A systematic review. AB - OBJECTIVE: To evaluate the evidence for, and clinical relevance of, immediate and long-term effects of trunk restraint during reach-to-grasp training poststroke on movement patterns and functional abilities within the framework of the International Classification of Functioning, Disability and Health. DATA SOURCES: PubMed, Web of Science, CINAHL, Embase, PEDro, Cochrane Library (publication dates January 1985 to March 2015). STUDY SELECTION: Randomized controlled trials comparing training using trunk restraint with any other exercise training. DATA EXTRACTION: Data were extracted by one researcher and checked by two other researchers. The Cochrane Collaboration's tool for assessing risk of bias and the Physiotherapy Evidence Database scale were used by two researchers to assess study quality and risk of bias. DATA SYNTHESIS: Eight studies met the inclusion criteria. Five studies found better recovery of movement patterns (trunk displacement, elbow extension, and/or shoulder flexion - body function/structure) at post-test in the experimental compared with the control groups. Functional abilities (activity/participation) improved more in the experimental groups in 3 studies at post-test. Long-term effects were found in one study after 4 weeks. CONCLUSION: Trunk restraint has immediate and some long-term effects in adults with chronic stroke. However, these effects are not consistently clinically relevant when referring to minimal detectable change or minimal clinically important difference values. PMID- 27008370 TI - Right and left ventricular assist devices support and liver dysfunction: prognostic and therapeutic implications. AB - PURPOSE OF REVIEW: Advanced heart failure is a chronic, systemic disease, which affects other organs in ways that are incompletely understood. Patients with advanced heart failure commonly develop congestive hepatopathy, which may lead to progressive hepatic injury and fibrosis. Because the independent adverse effects of hepatic dysfunction on early and late outcomes after continuous flow left ventricular assist devices have also not been entirely demonstrated, we review its impact on this patient population. RECENT FINDINGS: Although early mortality is increased in patients with significantly elevated total bilirubin before implant, early improvement in hepatic function is consistently observed following left ventricular assist device (LVAD) implantation, and this early improvement remains stable during late follow-up. Furthermore, a growing experience with expanded application of LVAD therapy in special patient populations, such as those with restrictive cardiomyopathy or congenital heart disease, demonstrates improved outcomes with LVAD compared with continued medical therapy. Although these outcomes are encouraging in the context of hepatic dysfunction not being considered a precluding factor in isolation, careful patient selection and preoperative optimization should be employed to ensure acceptable risk and a durable outcome. SUMMARY: Significant preoperative hepatic dysfunction can increase early mortality in patients undergoing LVAD implant, but long-term outcomes in early survivors demonstrate improvement in measures of hepatic function, which is maintained during follow-up. Numerous perioperative considerations are imperative to optimize to ensure a durable outcome with LVAD in these patients. PMID- 27008371 TI - Chronic ventricular assist device support: surgical innovation. AB - PURPOSE OF REVIEW: Ventricular assist device (VAD) therapy is currently one of the fastest-developing fields in cardiac surgery. Consistently improved technology, research, and gain of clinical experience have established VADs as an important option for the treatment of congestive heart failure. During the past year, novel devices and less invasive surgical procedures have been revolutionizing this field. The purpose of this manuscript is to review these innovations with special emphasis on device-related surgery. RECENT FINDINGS: Device miniaturization has enabled less invasive VAD surgery, excluding the need for full sternotomy. Recent data show that intrahospital survival rates following less invasive VAD implantation are surpassing 90%. Secondly, two new devices, Heartmate 3 and MVAD, are being applied and tested for clinical application. In this context, the Heartmate 3 CE mark study recently concluded with excellent outcomes and without any pump thrombosis or device malfunctions. SUMMARY: The first clinical results of the newest generation of VADs are very promising compared with old-generation devices. Furthermore, less invasive surgery is becoming a standard for the implantation, exchange, or explantation of left VADs. The joint venture of improved technology and innovative surgical techniques will push this field forward to even better outcomes and reduced complication rates. PMID- 27008372 TI - Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications. AB - The natural product staurosporine is a high-affinity inhibitor of nearly all mammalian protein kinases. The labelling of staurosporine has proven effective as a means of generating protein kinase research tools. Most tools have been generated by acylation of the 4'-methylamine of the sugar moiety of staurosporine. Herein we describe the alkylation of this group as a first step to generate a fluorescently labelled staurosporine. Following alkylation, a polyethylene glycol linker was installed, allowing subsequent attachment of fluorescein. We report that this fluorescein-staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest. PMID- 27008373 TI - The prevalence of genotypes that determine resistance to macrolides, lincosamides, and streptogramins B compared with spiramycin susceptibility among erythromycin-resistant Staphylococcus epidermidis. AB - Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, can be regarded as potential reservoirs of resistance genes for pathogenic strains, e.g., Staphylococcus aureus. The aim of this study was to assess the prevalence of different resistance phenotypes to macrolide, lincosamide, and streptogramins B (MLSB) antibiotics among erythromycin-resistant S. epidermidis, together with the evaluation of genes promoting the following different types of MLSB resistance:ermA, ermB, ermC,msrA, mphC, and linA/A'. Susceptibility to spiramycin was also examined. Among 75 erythromycin-resistantS. epidermidis isolates, the most frequent phenotypes were macrolides and streptogramins B (MSB) and constitutive MLSB (cMLSB). Moreover, all strains with the cMLSB phenotype and the majority of inducible MLSB (iMLSB) isolates were resistant to spiramycin, whereas strains with the MSB phenotype were sensitive to this antibiotic. The D-shape zone of inhibition around the clindamycin disc near the spiramycin disc was found for some spiramycin-resistant strains with the iMLSB phenotype, suggesting an induction of resistance to clindamycin by this 16-membered macrolide. The most frequently isolated gene was ermC, irrespective of the MLSB resistance phenotype, whereas the most often noted gene combination wasermC, mphC, linA/A'. The results obtained showed that the genes responsible for different mechanisms of MLSB resistance in S. epidermidis generally coexist, often without the phenotypic expression of each of them. PMID- 27008374 TI - Primary dengue virus infections induce differential cytokine production in Mexican patients. AB - Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient's clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-gamma levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-alpha, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-alpha, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis. PMID- 27008376 TI - The Effects of Sex on Cardiopulmonary Responses to Acute Normobaric Hypoxia. AB - Boos, Christopher John, Adrian Mellor, John Paul O'Hara, Costas Tsakirides, and David Richard Woods. The effects of sex on cardiopulmonary responses to acute normobaric hypoxia. High Alt Med Biol. 17:108-115, 2016.- BACKGROUND: Acute hypoxia leads to a number of recognized changes in cardiopulmonary function, including acute increase in pulmonary artery systolic pressure. However, the comparative responses between men and women have been barely explored. METHODS: Fourteen young healthy adult Caucasian subjects were studied at sea-level rest and then after >150-minute exposure to acute normobaric hypoxia (NH) equivalent to 4800 m and again at sea-level rest at 2 hours post-NH exposure. Cardiac function, using transthoracic echocardiography, physiological variables, and Lake Louise Scores for acute mountain sickness (AMS) were collected. RESULTS: All subjects completed the study, and there was an equal balance of men (n = 7) and women (n = 7) who were well matched for age (25.9 +/- 3.2 vs. 27.3 +/- 4.4; p = 0.51). NH exposure led to a significant increase in AMS scores and heart rate, as well as a fall in oxygen saturation, systolic blood pressure, and stroke volume. Stroke volumes and cardiac output were overall significantly higher in men than in women, and acute NH heart rate was higher in women (80.3 +/- 10.2 vs. 69.7 +/- 10.7/min; p < 0.05). NH led to a significant fall in the estimated left ventricular filling pressure (E/E'), an increase in the septal A' and S' and septal and lateral isovolumic contractile velocities (ICVs), and a fall in the E'A'S' ratio. The mitral E, lateral ICV, and E' velocities were all higher in men. Acute NH led to a significant increase in right ventricular systolic pressure and pulmonary vascular resistance. There was no interaction between NH exposure and sex for any parameters measured. CONCLUSION: Despite several baseline differences between men and women, the cardiopulmonary effects of acute NH are consistent between men and women. PMID- 27008375 TI - Antifungal activity of extracts from Atacama Desert fungi against Paracoccidioides brasiliensis and identification of Aspergillus felis as a promising source of natural bioactive compounds. AB - Fungi of the genus Paracoccidioides are responsible for paracoccidioidomycosis. The occurrence of drug toxicity and relapse in this disease justify the development of new antifungal agents. Compounds extracted from fungal extract have showing antifungal activity. Extracts of 78 fungi isolated from rocks of the Atacama Desert were tested in a microdilution assay against Paracoccidioides brasiliensis Pb18. Approximately 18% (5) of the extracts showed minimum inhibitory concentration (MIC) values <= 125.0 ug/mL. Among these, extract from the fungus UFMGCB 8030 demonstrated the best results, with an MIC of 15.6 ug/mL. This isolate was identified as Aspergillus felis (by macro and micromorphologies, and internal transcribed spacer, beta-tubulin, and ribosomal polymerase II gene analyses) and was grown in five different culture media and extracted with various solvents to optimise its antifungal activity. Potato dextrose agar culture and dichloromethane extraction resulted in an MIC of 1.9 ug/mL against P. brasiliensis and did not show cytotoxicity at the concentrations tested in normal mammalian cell (Vero). This extract was subjected to bioassay-guided fractionation using analytical C18RP-high-performance liquid chromatography (HPLC) and an antifungal assay using P. brasiliensis. Analysis of the active fractions by HPLC-high resolution mass spectrometry allowed us to identify the antifungal agents present in the A. felis extracts cytochalasins. These results reveal the potential of A. felis as a producer of bioactive compounds with antifungal activity. PMID- 27008377 TI - Vanadyl complexes with dansyl-labelled di-picolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies. AB - Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs). Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15) with bridged di picolinic acid ligands. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration than the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells. PMID- 27008378 TI - Effect of Anodic Alumina Oxide Pore Diameter on the Crystallization of Poly(butylene adipate). AB - Poly(butylene adipate) (PBA) was infiltrated into the anodic alumina oxide (AAO) templates with the pore diameter of around 30, 70, and 100 nm and PBA nanotubes with different diameters were prepared. The crystallization and phase transition behavior of the obtained PBA nanotubes capped in the nanopores have been explored by using X-ray diffraction and differential scanning calorimetry. Only alpha-PBA crystals form in the bulk sample during nonisothermal crystallization. By contrast, predominant beta-PBA crystals form in the AAO templates. The beta-PBA crystals formed in the nanopores with pore diameter less than 70 nm prefer to adopt an orientation with their b-axis parallel to the long axis of the pore. During the melt recrystallization, it was found that the critical temperature (Tbeta), below which pure beta-crystals form, is 20 degrees C for bulk PBA. It drops down significantly with the pore diameter for the PBA in the AAO template. Moreover, the beta-crystals in the porous template exhibit larger lattice parameters compared with the bulk crystals. By monitoring the change of beta crystals in the heating process, it was found that beta-crystals in the AAO template with the pore diameter of 30 nm (D30) melt directly while the beta crystals transform to alpha-crystals in the template with the pore diameter of 100 nm (D100). The intensity of (020) Bragg peak of beta-crystals decreases at a similar rate in both D30 and D100 but disappears at a relatively lower temperature in D30. On the other hand, the beta(110) peak intensity of beta-PBA crystals formed in the D100 template decreases first at slower rate before alpha crystals appear, and then at a faster rate once the beta to alpha phase transition takes place. PMID- 27008380 TI - Phenotypic Variation in Mangrove Cuckoo (Coccyzus minor) across Its Geographic Range. AB - Mangrove Cuckoo (Coccyzus minor) exhibits substantial phenotypic variation across its geographic range, but the significance of this variation for taxonomy remains unresolved. Using measurements of bill size and ventral color recorded from 274 museum specimens, I found that variation in these traits was clinal. No named subspecies was reciprocally diagnosable from all others, and none was distinguishable from the nominate form, such that previously recognized subspecific distinctions are invalid. Greatest differences in phenotype occurred between populations in Florida, the Bahamas, and the Greater Antilles- characteristically small-billed--and those in the Lesser Antilles, which had larger bills. Phenotypically intermediate individuals on the geographically intermediate islands of Barbuda and Antigua linked these two extremes. Individuals intermediate in bill size and color also characterized populations from throughout the remainder of the range in northern South America and Middle America. Mechanisms maintaining the fairly pronounced phenotypic differences between nearby populations of Greater and Lesser Antillean birds are unknown, yet the geographic proximity of these populations suggests that they probably persist despite occasional gene flow, and may be adaptive. PMID- 27008379 TI - The association between S100A13 and HMGA1 in the modulation of thyroid cancer proliferation and invasion. AB - BACKGROUND: S100A13 and high mobility group A (HMGA1) are known to play essential roles in the carcinogenesis and progression of cancer. However, the correlation between S100A13 and HMGA1 during cancer progression is not yet well understood. In this study, we determined the effects of S100A13 on HMGA1 expression in thyroid cancer cells and examined the role of HMGA1 in thyroid cancer progression. METHODS: Stable ectopic S100A13 expression TT cellular proliferation was evaluated by nude mice xenografts assays. The effect of lentivirus-mediated S100A13 knockdown on thyroid cancer cellular oncogenic properties were evaluated by MTT, colony formation assays and transwell assays in TPC1 and SW579 cells. The effect of siRNA-mediated HMGA1 knockdown on thyroid cancer cellular proliferation and invasion were evaluated by MTT, colony formation assays and transwell assays. The tissue microarray was performed to investigate the correlation between S100A13 and HMGA1 expression in tumor tissues. RESULTS: The ectopic expression of S100A13 could increase tumor growth in a TT cell xenograft mouse model. Moreover, lentivirus-mediated S100A13 knockdown led to the inhibition of cellular oncogenic properties in thyroid cancer cells, and HMGA1 was found to be involved in the effect of S100A13 on thyroid cancer growth and invasion. Furthermore, siRNA mediated HMGA1 knockdown was proved to inhibit the growth of TPC1 cells and invasive abilities of SW579 cells. Clinically, it was revealed that both S100A13 and HMGA1 showed a higher expression levels in thyroid cancer cases compared with those in matched normal thyroid cases (P = 0.007 and P = 0.000); S100A13 and HMGA1 expressions were identified to be positively correlated (P = 0.004, R = 0.316) when analyzed regardless of thyroid cancer types. CONCLUSIONS: This is the first report for the association between HMGA1 and S100A13 expression in the modulation of thyroid cancer growth and invasion. Those results would provide an essential insight into the effect of S100A13 on carcinogenesis of thyroid tumor, rending S100A13 to be potential biological marker for the diagnosis of thyroid cancer. PMID- 27008381 TI - Enantioselective Degradation and Chiral Stability of Metalaxyl-M in Tomato Fruits. AB - Metalaxyl is an important chiral acetanilide fungicide, and the activity almost entirely originates from the R-enantiomer. Racemic metalaxyl has been gradually replaced by the enantiopure R-enantiomer (metalaxyl-M). In this study a chiral residue analysis method for metalaxyl and the metabolite metalaxyl acid was set up based on high-performance liquid chromatography tandem mass spectroscopy (HPLC MS/MS). The enantioselective degradation and chiral stability of metalaxyl-M in tomato fruits in two geographically distinct regions of China (Heilongjiang and Hunan Province) were evaluated and the enantioselectivity of metalaxyl acid was also investigated. Tomato plants grew under field conditions with a one-time spray application of metalaxyl-M wettable powder. It was found that R-metalaxyl was not chirally stable and the inactive S-metalaxyl was detected in tomato fruits. At day 40, S-metalaxyl derived from R-metalaxyl accounted for 32% and 26% of the total amount of metalaxyl, respectively. The metabolites R-metalaxyl acid and S-metalaxyl acid were both observed in tomato, and the ratio of S-metalaxyl acid to the sum of S- and R-metalaxyl acid was 36% and 28% at day 40, respectively. For both metalaxyl and metalaxyl acid, the half-life of the S enantiomer was longer than the R-enantiomer. The results indicated that the enantiomeric conversion should be considered in the bioactivity evaluation and environmental pollution assessment. Chirality 28:382-386, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27008382 TI - Vitamin E, gamma-tocotrienol, Protects Against Buthionine Sulfoximine-Induced Cell Death by Scavenging Free Radicals in SH-SY5Y Neuroblastoma Cells. AB - The induction of reactive oxygen species (ROS) to selectively kill cancer cells is an important feature of radiotherapy and various chemotherapies. Depletion of glutathione can induce apoptosis in cancer cells or sensitize them to anticancer treatments intended to modulate ROS levels. In contrast, antioxidants protect cancer cells from oxidative stress-induced cell death by scavenging ROS. The role of exogenous antioxidants in cancer cells under oxidative insults remains controversial and unclear. This study aimed to identify protective pathways modulated by gamma-tocotrienol (gammaT3), an isomer of vitamin E, in human neuroblastoma SH-SY5Y cells under oxidative stress. Using buthionine sulfoximine (BSO) as an inhibitor of glutathione synthesis, we found that BSO treatment reduced the viability of SH-SY5Y cells. BSO induced cell death by increasing apoptosis, decreased the level of reduced glutathione (GSH), and increased ROS levels in SH-SY5Y cells. Addition of gammaT3 increased the viability of BSO treated cells, suppressed apoptosis, and decreased the ROS level induced by BSO, while the GSH level was unaffected. These results suggest that decreasing GSH levels by BSO increased ROS levels, leading to apoptosis in SH-SY5Y cells. gammaT3 attenuated the BSO-induced cell death by scavenging free radicals. PMID- 27008383 TI - The Genus Cladophora Kutzing (Ulvophyceae) as a Globally Distributed Ecological Engineer. AB - The green algal genus Cladophora forms conspicuous nearshore populations in marine and freshwaters worldwide, commonly dominating peri-phyton communities. As the result of human activities, including the nutrient pollution of nearshore waters, Cladophora-dominated periphyton can form nuisance blooms. On the other hand, Cladophora has ecological functions that are beneficial, but less well appreciated. For example, Cladophora has previously been characterized as an ecological engineer because its complex structure fosters functional and taxonomic diversity of benthic microfauna. Here, we review classic and recent literature concerning taxonomy, cell biology, morphology, reproductive biology, and ecology of the genus Cladophora, to examine how this alga functions to modify habitats and influence littoral biogeochemistry. We review the evidence that Cladophora supports large, diverse populations of microalgal and bacterial epiphytes that influence the cycling of carbon and other key elements, and that the high production of cellulose and hydrocarbons by Cladophora-dominated periphyton has the potential for diverse technological applications, including wastewater remediation coupled to renewable biofuel production. We postulate that well-known aspects of Cladophora morphology, hydrodynamically stable and perennial holdfasts, distinctively branched architecture, unusually large cell and sporangial size and robust cell wall construction, are major factors contributing to the multiple roles of this organism as an ecological engineer. PMID- 27008384 TI - Low Salinity Predation Refugia Could Cause HAB Initiation. PMID- 27008385 TI - Broad Salinity Tolerance as a Refuge from Predation in the Harmful Raphidophyte Alga Heterosigma akashiwo (Raphidophyceae). AB - The ability of harmful algal species to form dense, nearly monospecific blooms remains an ecological and evolutionary puzzle. We hypothesized that predation interacts with estuarine salinity gradients to promote blooms of Heterosigma akashiwo (Y. Hada) Y. Hada ex Y. Hara et M. Chihara, a cosmopolitan toxic raphidophyte. Specifically, H. akashiwo's broad salinity tolerance appears to provide a refuge from predation that enhances the net growth of H. akashiwo populations through several mechanisms. (1) Contrasting salinity tolerance of predators and prey. Estuarine H. akashiwo isolates from the west coast of North America grew rapidly at salinities as low as six, and distributed throughout experimental salinity gradients to salinities as low as three. In contrast, survival of most protistan predator species was restricted to salinities >15. (2) H. akashiwo physiological and behavioral plasticity. Acclimation to low salinity enhanced H. akashiwo's ability to accumulate and grow in low salinity waters. In addition, the presence of a ciliate predator altered H. akashiwo swimming behavior, promoting accumulation in low-salinity surface layers inhospitable to the ciliate. (3) Negative effects of low salinity on predation processes. Ciliate predation rates decreased sharply at salinities <25 and, for one species, H. akashiwo toxicity increased at low salinities. Taken together, these behaviors and responses imply that blooms can readily initiate in low salinity waters where H. akashiwo would experience decreased predation pressure while maintaining near maximal growth rates. The salinity structure of a typical estuary would provide this HAB species a unique refuge from predation. Broad salinity tolerance in raphidophytes may have evolved in part as a response to selective pressures associated with predation. PMID- 27008386 TI - Characterization of a High Affinity Phytochelatin Synthase from The Cd-Utilizing Marine Diatom Thalassiosira pseudonana. AB - Phytochelatin synthase (PC synthase) is the enzyme that catalyzes the production of phytochelatins, peptides of the structure (gamma-Glu-Cys)n -Gly, where n = 2 11, from the sulfhydryl-containing tripeptide glutathione, in response to elevated metal exposure. Biochemical utilization of Cd in the marine diatom Thalassiosira weissfloggi, as well as unusually high ratios of PC to Cd in some Thalassiosira species including T. pseudonana Hasle et Heimdal, motivated the characterization of T. pseudonana PC synthase 1 (TpPCS1). This enzyme is the product of one of three genes in the T. pseudonana genome predicted to encode for a PC synthase based on its homology to canonical PC synthases previously examined. TpPCS1 was cloned, expressed in Escherichia coli and purified under both aerobic and anaerobic conditions. TpPCS1 exhibits several characteristics that set it distinctly apart from the well-studied PC synthase, Arabidopsis thaliana PCS1 (AtPCS1). It is extremely sensitive to oxidation, which suppresses activity, and it is readily inhibited by the addition of Cd in the absence of thiolate ligands. TpPCS1 also has significantly greater affinity for one of its key substrates, the bis-glutathionato-Cd complex. TpPCS1 kinetics is best described by a ternary complex model, as opposed to the ping-pong model used to describe AtPCS1 kinetics. The findings indicate that although the function of TpPCS1 is synonymous to that of AtPCS1, its divergent biochemistry suggests adaptation of this enzyme to the distinct trace metal chemistry of the marine environment and the unique physiological needs of T. pseudonana. PMID- 27008387 TI - Comparison of Freshwater Diatom Assemblages from a High Arctic Oasis to Nearby Polar Desert Sites and Their Application to Environmental Inference Models. AB - Arctic oases are regions of atypical warmth and relatively high biological production and diversity. They are small in area (<5 km(2) ) and uncommon in occurrence, yet they are relatively well studied due to the abundance of plant and animal life contained within them. A notable exception is the lack of research on freshwater ecosystems within polar oases. Here, we aim to increase our understanding of freshwater diatom ecology in polar oases. Diatoms were identified and enumerated from modern sediments collected in 23 lakes and ponds contained within the Lake Hazen oasis on Ellesmere Island, and compared with diatom assemblages from 29 sites located outside of the oasis across the northern portion of the island. There were significant differences in water chemistry variables between oasis and northern sites, with oasis sites having higher conductivity and greater concentrations of nutrients and related variables such as dissolved organic carbon (DOC). Taxa across all sites were typical of those recorded in Arctic freshwaters, with species from the genera Achnanthes sensu lato, Fragilaria sensu lato, and Nitzschia dominating the assemblages. A correspondence analysis (CA) ordination showed that oasis sites generally plotted separately from the northern sites, although the sites also appear to plot separately based on whether they were lakes or ponds. Canonical correspondence analysis (CCA) identified specific conductivity, DOC, and SiO2 as explaining significant (P < 0.05) and additional amounts of variation in the diatom data set. The most robust diatom-based inference model was generated for DOC, which will provide useful reconstructions on long-term changes in paleo-optics of high Arctic lakes. PMID- 27008388 TI - Environmental Optima for Seven Strains of Pseudochattonella (Dictyochophyceae, Heterokonta). AB - The ichthyotoxic flagellate Pseudochattonella has formed recurrent blooms in the North Sea, Skagerrak and Kattegat since 1998. Five strains of Pseudochattonella farcimen and two strains of P. verruculosa were examined in an assay comparing the light response of specific growth rates over a range of temperatures and salinities to get further knowledge on the autecology of members of this genus. Temperature optima were lower in P. farcimen (9 degrees C-15 degrees C) than in P. verruculosa (12 degrees C-20 degrees C). P. farcimen also showed a somewhat lower salinity optimum (18-26) than P. verruculosa (20-32). All strains showed light-dependent growth responses reaching saturation between 18 and 52 MUmol . photons . m(-2) . s(-1) at optimal temperature and salinity conditions. Compensation point estimates ranged from 4.2 to 15 MUmol . photons . m(-2) . s( 1) . Loss rates increased with temperature and were lowest at salinities close to optimal growth conditions. Blooms of P. farcimen have been recorded in nature under conditions more similar to those minimizing loss rates rather than those maximizing growth rates in our culture study. PMID- 27008389 TI - Thermal Acclimation of Respiration and Photosynthesis in the Marine Macroalga Gracilaria lemaneiformis (Gracilariales, Rhodophyta). AB - The responses of respiration and photosynthesis to temperature fluctuations in marine macroalgae have the potential to significantly affect coastal carbon fluxes and sequestration. In this study, the marine red macroalga Gracilaria lemaneiformis was cultured at three different temperatures (12, 19, and 26 degrees C) and at high- and low-nitrogen (N) availability, to investigate the acclimation potential of respiration and photosynthesis to temperature change. Measurements of respiratory and photosynthetic rates were made at five temperatures (7 degrees C-33 degrees C). An instantaneous change in temperature resulted in a change in the rates of respiration and photosynthesis, and the temperature sensitivities (i.e., the Q10 value) for both the metabolic processes were lower in 26 degrees C-grown algae than 12 degrees C- or 19 degrees C-grown algae. Both respiration and photosynthesis acclimated to long-term changes in temperature, irrespective of the N availability under which the algae were grown; respiration displayed strong acclimation, whereas photosynthesis only exhibited a partial acclimation response to changing growth temperatures. The ratio of respiration to gross photosynthesis was higher in 12 degrees C-grown algae, but displayed little difference between the algae grown at 19 degrees C and 26 degrees C. We propose that it is unlikely that respiration in G. lemaneiformis would increase significantly with global warming, although photosynthesis would increase at moderately elevated temperatures. PMID- 27008390 TI - A Molecular Survey of Ulva (Chlorophyta) in Temperate Australia Reveals Enhanced Levels of Cosmopolitanism. AB - The green algal genus Ulva includes a speciose group of marine macroalgae inhabiting shallow seas worldwide. Although algal blooms in Asia highlight the opportunistic nature of several "nuisance" species, recent research clearly reveals important positive benefits of Ulva. Applied research requires accurate, reliable, and rapid identification, however, identification of Ulva spp. has met with con-siderable difficulty. Consequently, many have turned to molecular markers to aid in taxonomy. Previous studies of plants and algae have relied heavily on ITS and rbcL. Recently, tufA has been presented as a suitable barcoding gene to facilitate species-level identification of green macroalgae and it is used here to explore the diversity of Ulva spp. in temperate Australia. Ninety Ulva specimens collected from 38 sites across five states were sequenced for this gene region with exemplars from each genetic group also sequenced for rbcL to test for congruence. Collections of Australian Ulva spp. were compared to samples from Asia and North America and exhibited trends consistent with recent studies in terms of species relationships. Results support an overwhelmingly cosmopolitan flora in temperate Australia that contrasts with other Australasian surveys of Ulva that report a greater number of endemics and new species. Four new records, as well as numerous range extensions for taxa already known from the country, are documented. Evidence for three nonindigenous Ulva species in temperate Australia is discussed. PMID- 27008391 TI - Phylogenetic Reappraisal of the Genus Monomorphina (Euglenophyceae) Based on Molecular and Morphological Data. AB - A morphological and molecular examination of the genus Monomorphina was conducted on 46 strains isolated mainly from Korea. The strains were divided into two types based on morphological data: Monomorphina aenigmatica and M. pyrum - like species. Phylogenetic analysis based on a combined data set of nuclear SSU and LSU and plastid SSU and LSU rDNA showed that the strains could be divided into eight clades: Clade A of M. aenigmatica, Clade B of the isolates (M. pyropsis) from Michigan, USA, Clade C of M. pseudopyrum, Clade D of the isolates (M. pyroria) from Bremen, Germany, Clade E of M. soropyrum, Clade F of M. pyriformis, Clade G of M. parapyrum, and Clade H of M. pyrum. Six of these clades came from strains that would be considered M. pyrum sensu Kosmala et Zakrys, one of which could be recognized as a traditional species (M. pyrum) and five were designated as new species; each species had unique molecular signatures at nr SSU rDNA helix 17 and 17' and spacer E23_14'-E23_15. The species of Monomorphina had a wide range of genetic diversity with interspecies sequence similarity of 85.6%-97.1% and intraspecies similarity of 96.4%-99.9%. Our results suggested that genetic diversity found in the M. pyrum complex justifies the recognition of a minimum of eight species within this genus, based on specific molecular signatures and gene divergence of the nr SSU rDNA sequences. PMID- 27008392 TI - Cryptic Speciation in the Genus Cryptoglena (Euglenaceae) Revealed by Nuclear and Plastid SSU and LSU rRNA Gene. AB - The photosynthetic euglenoid genus Cryptoglena is differentiated from other euglenoid genera by having a longitudinal sulcus, one chloroplast, two large trough-shaped paramylon plates positioned between the chloroplast and pellicle, and lack of metaboly. The genus contains only two species. To understand genetic diversity and taxonomy of Cryptoglena species, we analyzed molecular and morphological data from 25 strains. A combined data set of nuclear SSU and LSU and plastid SSU and LSU rRNA genes was analyzed using Bayesian, maximum likelihood, maximum parsimony, and distance (neighbor joining) methods. Although morphological data of all strains showed no significant species-specific pattern, molecular data segregated the taxa into five clades, two of which represented previously known species: C. skujae and C. pigra, and three of which were designated as the new species, C. soropigra, C. similis, and C. longisulca. Each species had unique molecular signatures that could be found in the plastid SSU rRNA Helix P23_1 and LSU rRNA H2 domain. The genetic similarity of intraspecies based on nr SSU rDNA ranged from 97.8% to 100% and interspecies ranged from 95.3% to 98.9%. Therefore, we propose three new species based on specific molecular signatures and gene divergence of the nr SSU rDNA sequences. PMID- 27008393 TI - A Molecular Phylogenetic Study of the Tribe Corallineae (Corallinales, Rhodophyta) with an Assessment of Genus-Level Taxonomic Features and Descriptions of Novel Genera. AB - A multigene phylogeny using COI-5P (mitochondrial cytochrome c oxidase subunit 1), psbA (PSII reaction center protein D1), and EF2 (elongation factor 2) sequence data for members of the tribe Corallineae was constructed to assess generic boundaries. We determined that traditional reliance on conceptacle position as an indicator of generic affinities in the Corallineae is not supported and taxonomic changes are required. We found that species currently assigned to Pseudolithophyllum muricatum resolved within the Corallineae in all analyses. This is the first record of crustose members in the subfamily Corallinoideae. Further-more, the genus Serraticardia was polyphyletic; we propose to synonomize Serraticardia with Corallina, transfer the type species S. maxima to Corallina (C. maxima (Yendo) comb. nov.), and describe the new genus Johansenia for S. macmillanii (J. macmillanii (Yendo) comb. nov.). Our molecular data also indicate that species in the genus Marginisporum have evolutionary affinities among species of Corallina and these genera should also be synonymized. This necessitates the combinations C. aberrans (Yendo) comb. nov. for M. aberrans (Yendo) Johansen & Chihara, C. crassissima (Yendo) comb. nov. for M. crassissimum (Yendo) Ganesan, and C. declinata (Yendo) comb. nov. for M. declinata (Yendo) Ganesan. Corallina elongata was divergent from all other members of Corallina and is transferred to a new genus, Ellisolandia (E. elongata (J. Ellis & Solander) comb. nov). In addition, COI-5P and internal transcribed spacer (ITS) data combined with morphological characters were used to establish that rather than the four Corallina species recognized in Canada, there are nine. PMID- 27008394 TI - Morphology and Phylogenetic Position of the Freshwater Green Microalgae Chlorochytrium (Chlorophyceae) and Scotinosphaera (Scotinosphaerales, ord. nov., Ulvophyceae). AB - The green algal family Chlorochytriaceae comprises relatively large coccoid algae with secondarily thickened cell walls. Despite its morphological distinctness, the family remained molecularly uncharacterized. In this study, we investigated the morphology and phylogenetic position of 16 strains determined as members of two Chlorochytriaceae genera, Chlorochytrium and Scotinosphaera. The phylogenetic reconstructions were based on the analyses of two data sets, including a broad, concatenated alignment of small subunit rDNA and rbcL sequences, and a 10-gene alignment of 32 selected taxa. All analyses revealed the distant relation of the two genera, segregated in two different classes: Chlorophyceae and Ulvophyceae. Chlorochytrium strains were inferred in two distinct clades of the Stephanosphaerinia clade within the Chlorophyceae. Whereas clade A morphologically fits the description of Chlorochytrium, the strains of clade B coincide with the circumscription of the genus Neospongiococcum. The Scotinosphaera strains formed a distinct and highly divergent clade within the Ulvophyceae, warranting the recognition of a new order, Scotinosphaerales. Morphologically, the order is characterized by large cells bearing local cell wall thickenings, pyrenoid matrix dissected by numerous anastomosing cytoplasmatic channels, sporogenesis comprising the accumulation of secondary carotenoids in the cell periphery and almost simultaneous cytokinesis. The close relationship of the Scotinosphaerales with other early diverging ulvophycean orders enforces the notion that nonmotile unicellular freshwater organisms have played an important role in the early diversification of the Ulvophyceae. PMID- 27008395 TI - Species Diversity, Phylogeny and Large Scale Biogeographic Patterns of the Genus Padina (Phaeophyceae, Dictyotales). AB - The brown algal genus Padina (Dictyotales, Phaeophyceae) is distributed worldwide in tropical and temperate seas. Global species diversity and distribution ranges, however, remain largely unknown. Species-level diversity was reassessed using DNA based, algorithmic species delineation techniques based on cox3 and rbcL sequence data from 221 specimens collected worldwide. This resulted in estimates ranging from 39 to 61 putative species (ESUs), depending on the technique as well as the locus. We discuss the merits, potential pitfalls, and evolutionary and biogeographic significance of algorithmic species delineation. We unveil patterns whereby ESUs are in all but one case restricted to either the Atlantic or Indo Pacific Ocean. Within ocean basins we find evidence for the vast majority of ESUs to be confined to a single marine realm. Exceptions, whereby ESUs span up to three realms, are located in the Indo-Pacific Ocean. Patterns of range-restricted species likely arise by repeated founder events and subsequent peripatric speciation, hypothesized to dominate speciation mechanisms for coastal marine organisms in the Indo-Pacific. Using a three-gene (cox3, psaA and rbcL), relaxed molecular clock phylogenetic analysis we estimated divergence times, providing a historical framework to interpret biogeographic patterns. PMID- 27008396 TI - Morphology and Phylogeny of Prorocentrum texanum sp. nov. (Dinophyceae): A New Toxic Dinoflagellate from the Gulf of Mexico Coastal Waters Exhibiting Two Distinct Morphologies. AB - A new planktonic species of Prorocentrum is described from the Gulf of Mexico. First observed with the Imaging FlowCytobot, Prorocentrum texanum sp. nov. was characterized using LM, SEM, and TEM along with sequencing of the SSU, LSU, and ITS ribosomal regions and the mitochondrial cob and cox1 regions. P. texanum sp. nov. is a round to oval bivalvate dinoflagellate, with a prominent anterior, serrated solid flange on periflagellar a platelet and an opposing short, flat flange on the h platelet. The periflagellar area consists of 10 platelets. Both left and right valves have shallow round depressions and two-sized valve pores. The anterior ejectosome pore pattern differs between the left and right valve in relation to the periflagellar area and margins. Ten to eleven rows of tangential ejectosome pores are present on each valve. P. texanum sp. nov. has two varieties which exhibit distinct morphotypes, one round to oval (var. texanum) and the other pointed (var. cuspidatum). P. texanum var. cuspidatum is morphologically similar to P. micans in surface markings, but is smaller, and has a serrated periflagellar flange, and is genetically distinct from P. micans. Cytologically, P. texanum has two parietal chlo-roplasts, each with a compound, interlamellar pyrenoid, trichocysts, fibrous vesicles that resemble mucocysts, pusules, V- to U shaped posterior nucleus, golgi, and tubular mitochondria. No genetic difference was found between the two varieties in the five genes examined. Phylogenetic analysis of the SSU, LSU, and ITS ribosomal regions place P. texanum sp. nov. as a sister group to P. micans. One isolate of P. texanum var. texanum produces okadaic acid. PMID- 27008397 TI - Nitrogen Utilization and Toxin Production by Two Diatoms of the Pseudo-nitzschia pseudodelicatissima Complex: P. cuspidata and P. fryxelliana. AB - The toxigenic diatom Pseudo-nitzschia cuspidata, isolated from the U.S. Pacific Northwest, was examined in unialgal batch cultures to evaluate domoic acid (DA) toxicity and growth as a function of light, N substrate, and growth phase. Experiments conducted at saturating (120 MUmol photons . m(-2) . s(-1) ) and subsaturating (40 MUmol photons . m(-2) . s(-1) ) photosynthetic photon flux density (PPFD), demonstrate that P. cuspidata grows significantly faster at the higher PPFD on all three N substrates tested [nitrate (NO3 (-) ), ammonium (NH4 (+) ), and urea], but neither cellular toxicity nor exponential growth rates were strongly associated with one N source over the other at high PPFD. However, at the lower PPFD, the exponential growth rates were approximately halved, and the cells were significantly more toxic regardless of N substrate. Urea supported significantly faster growth rates, and cellular toxicity varied as a function of N substrate with NO3 (-) -supported cells being significantly more toxic than both NH4 (+) - and urea-supported cells at the low PPFD. Kinetic uptake parameters were determined for another member of the P. pseudodelicatissima complex, P. fryxelliana. After growth of these cells on NO3 (-) they exhibited maximum specific uptake rates (Vmax ) of 22.7, 29.9, 8.98 * 10(-3) . h(-1) , half-saturation constants (Ks ) of 1.34, 2.14, 0.28 MUg-at N . L(-1) , and affinity values (alpha) of 17.0, 14.7, 32.5 * 10(-3) . h(-1) /(MUg-at N . L(-1) ) for NO3 (-) , NH4 (+) and urea, respectively. These labo-ratory results demonstrate the capability of P. cuspidata to grow and produce DA on both oxidized and reduced N substrates during both exponential and stationary growth phases, and the uptake kinetic results for the pseudo-cryptic species, P. fryxelliana suggest that reduced N sources from coastal runoff could be important for maintenance of these small pennate diatoms in U.S. west coast blooms, especially during times of low ambient N concentrations. PMID- 27008398 TI - Cloning, Expression and Characterization of the delta-carbonic Anhydrase of Thalassiosira weissflogii (Bacillariophyceae). AB - Carbonic anhydrase (CA) is a ubiquitous metalloenzyme responsible for accelerating the interconversion of CO2 and bicarbonate. Although CAs are involved in a broad range of biochemical processes involving carboxylation or decarboxylation reactions, they are of special interest due to their role in photosynthetic CO2 assimilation in marine phytoplankton, especially under low-CO2 conditions. Several phylogenetically independent classes of CAs have been identified in a variety of marine phytoplankton. TWCA1, first discovered in Thalassiosira weissflogii (Grunow) G. Fryxell & Hasle, is the founding member of the delta-class of CAs; these appear to be extracellular enzymes, but are still relatively poorly characterized. To date, it has remained uncertain whether TWCA1 possesses true CA activity due to the difficulty in producing a functional protein in a heterologous expression system. Herein we describe the fusion of a full-length open reading frame of TWCA1 to the coding sequence of a self-splicing intein in a pTWIN2 expression vector that has allowed successful production of a functional enzyme in Escherichia coli. Assay of the recombinant protein shows that TWCA1 is a catalytically active delta-CA possessing both CO2 hydration and esterase activity. PMID- 27008399 TI - Tetraflagellochloris mauritanica gen. et sp. nov. (Chlorophyceae), a New Flagellated Alga from the Mauritanian Desert: Morphology, Ultrastructure, and Phylogenetic Framing. AB - Morphological, ultrastructural, and molecular-sequence data were used to assess the phylogenetic position of a tetraflagellate green alga isolated from soil samples of a saline dry basin near F'derick, Mauritania. This alga can grow as individual cells or form non-coenobial colonies of up to 12 individuals. It has a parietal chloroplast with an embedded pyrenoid covered by a starch sheath and traversed by single parallel thylakoids, and an eyespot located in a parietal position opposite to the flagellar insertion. Lipid vacuoles are present in the cytoplasm. Microspectroscopy indicated the presence of chlorophylls a and b, with lutein as the major carotenoid in the chloroplast, while the eyespot spectrum has a shape typical of green-algal eyespots. The cell has four flagella, two of them long and two considerably shorter. Sequence data from the 18S rRNA gene and ITS2 were obtained and compared with published sequences for green algae. Results from morphological and ultrastructural examinations and sequence analysis support the placement of this alga in the Chlorophyceae, as Tetraflagellochloris mauritanica L. Barsanti et A. Barsanti, gen. et sp. nov. PMID- 27008400 TI - Cyclophilin Participates in Responding to Stress Situations in Porphyra haitanensis (Bangiales, Rhodophyta). AB - Porphyra haitanensis (T. J. Chang & B. F. Zheng) is an important economic alga found off the southern coast of China. It has evolved a strong tolerance against stress, which is an important survival characteristic. Cyclophilin has been shown to be involved in the stress response of plants and algae. To investigate the tolerance against stress in Porphyra, we isolated the cyclophilin PhCYP18 gene (Accession number JQ413239) and measured its expression over different generations and stress conditions. In P. haitanensis, cyclophilin PhCYP18 accumulated more in the filamentous sporophyte generation than in the blade gametophyte generation. This difference was thought to be due to harsh environments and a gene dosage effect. It has been found, however, that PhCYP18 expression was dysregulated in blades under high salt stress, strong irradiance stress and multifactorial stress compared to blades under normal conditions. Moreover, the changes were not linearly related to the degree of stress. It was therefore thought that PhCYP18 actively responded to stress situations and induced strong stress tolerance, which is evident in P. haitanensis. PMID- 27008401 TI - Algal Parasite Herpodiscus durvillaeae (Phaeophyceae: Sphacelariales) Inferred to have Traversed the Pacific Ocean with its Buoyant Host. AB - The parasitic phaeophycean endophyte Herpodiscus durvillaeae (Lindauer) G. R. South has previously only been recorded from New Zealand, in association with a single host species, Durvillaea antarctica (Chamisso) Hariot (southern bull kelp). Here we use DNA sequence data from plastid and nuclear markers (chloroplast rbcL, ribosomal LSU, and a nuclear pseudogene copy of COI) to test for the presence of H. durvillaeae beyond the New Zealand region, and on host species other than D. antarctica. Analyses of samples from the Falkland Islands confirm the first record of H. durvillaeae from the Atlantic Ocean. We report that Falkland Islands H. durvillaeae are genetically indistinguishable from samples of this species from New Zealand's sub-Antarctic Campbell Island, suggesting recent dispersal of the parasite across the Pacific Ocean, presumably by rafting with its buoyant macroalgal host. We also here record H. durvillaeae from New Zealand endemics Durvillaea poha Fraser et al. and D. willana Lindauer. PMID- 27008402 TI - Identification of a Marine Cyanophage in a Protist Single-cell Metagenome Assembly. AB - Analysis of microbial biodiversity is hampered by a lack of reference genomes from most bacteria, viruses, and algae. This necessitates either the cultivation of a restricted number of species for standard sequencing projects or the analysis of highly complex environmental DNA metagenome data. Single-cell genomics (SCG) offers a solution to this problem by constraining the studied DNA sample to an individual cell and its associated symbionts, prey, and pathogens. We used SCG to study marine heterotrophic amoebae related to Paulinella ovalis (A. Wulff) P.W. Johnson, P.E. Hargraves & J.M. Sieburth (Rhizaria). The genus Paulinella is best known for its photosynthetic members such as P. chromatophora Lauterborn that is the only case of plastid primary endosymbiosis known outside of algae and plants. Here, we studied the phagotrophic sister taxa of P. chromatophora that are related to P. ovalis and found one SCG assembly to contain alpha-cyanobacterial DNA. These cyanobacterial contigs are presumably derived from prey. We also uncovered an associated cyanophage lineage (provisionally named phage PoL_MC2). Phylogenomic analysis of the fragmented genome assembly suggested a minimum genome size of 200 Kbp for phage PoL_MC2 that encodes 179 proteins and is most closely related to Synechococcus phage S-SM2. For this phage, gene network analysis demonstrates a highly modular genome structure typical of other cyanophages. Our work demonstrates that SCG is a powerful approach for discovering algal and protist biodiversity and for elucidating biotic interactions in natural samples. PMID- 27008403 TI - Rac1/beta-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9. AB - BACKGROUND/AIMS: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs). Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. METHODS: We measured the activity of Rac1 and its downstream targets, beta-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the beta catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and beta-catenin on trophoblast invasion. RESULTS: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the beta-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down-regulated the expression of beta-catenin in HTR 8/SVneo cells, demonstrating that beta-catenin is a downstream effector of Rac1 in trophoblast invasion. CONCLUSION: Our data suggest that Rac1-mediated activation of beta-catenin might regulate Snail and MMP9 expression subsequently promoting trophoblast invasion in pregnancy. PMID- 27008404 TI - Cerebrospinal Fluid Hypocretin-1 (Orexin-A) Level Fluctuates with Season and Correlates with Day Length. AB - The hypocretin/orexin neuropeptides (hcrt) are key players in the control of sleep and wakefulness evidenced by the fact that lack of hcrt leads to the sleep disorder Narcolepsy Type 1. Sleep disturbances are common in mood disorders, and hcrt has been suggested to be poorly regulated in depressed subjects. To study seasonal variation in hcrt levels, we obtained data on hcrt-1 levels in the cerebrospinal fluid (CSF) from 227 human individuals evaluated for central hypersomnias at a Danish sleep center. The samples were taken over a 4 year timespan, and obtained in the morning hours, thus avoiding impact of the diurnal hcrt variation. Hcrt-1 concentration was determined in a standardized radioimmunoassay. Using biometric data and sleep parameters, a multivariate regression analysis was performed. We found that the average monthly CSF hcrt-1 levels varied significantly across the seasons following a sine wave with its peak in the summer (June-July). The amplitude was 19.9 pg hcrt/mL [12.8-26.9] corresponding to a 10.6% increase in midsummer compared to winter. Factors found to significantly predict the hcrt-1 values were day length, presence of snow, and proximity to the Christmas holiday season. The hcrt-1 values from January were much higher than predicted from the model, suggestive of additional factors influencing the CSF hcrt-1 levels such as social interaction. This study provides evidence that human CSF hcrt-1 levels vary with season, correlating with day length. This finding could have implications for the understanding of winter tiredness, fatigue, and seasonal affective disorder. This is the first time a seasonal variation of hcrt-1 levels has been shown, demonstrating that the hcrt system is, like other neurotransmitter systems, subjected to long term modulation. PMID- 27008405 TI - Quality of Life of Adult Patients With Attention-Deficit/Hyperactivity Disorder Taking Methylphenidate-Reply. PMID- 27008406 TI - Local Symmetry Effects in Actinide 4f X-ray Absorption in Oxides. AB - A systematic X-ray absorption study at actinide N6,7 (4f -> 6d transitions) edges was performed for light-actinide oxides including data obtained for the first time for NpO2, PuO2, and UO3. The measurements were supported by ab initio calculations based on local-density-approximation with added 5f-5f Coulomb interaction (LDA+U). Improved energy resolution compared to common experiments at actinide L(2,3) (2p -> 6d transitions) edges allowed us to resolve the major structures of the unoccupied 6d density of states (DOS) and estimate the crystal field splittings in the 6d shell directly from the spectra of light-actinide dioxides. The measurements demonstrated an enhanced sensitivity of the N(6,7) spectral shape to changes in the compound crystal structure. For nonstoichiometric NpO(2-x), the filling of the entire band gap with Np 6d states was observed thus supporting a phase coexistence of Np metal and stoichiometric NpO2 which is in agreement with the tentative Np-O phase diagram. PMID- 27008407 TI - Mismatch Amplification Mutation Assay Real-Time PCR Analysis of the Leptin Gene G2548A and A19G Polymorphisms and Serum Leptin in Infancy: A Preliminary Investigation. AB - Leptin is a hormone that regulates food intake and energy metabolism. Its coding gene (LEP) is one of the most promising candidates for obesity. Although some studies have detected associations of different single nucleotide polymorphisms (SNPs) in the LEP gene with serum leptin levels and obesity-related traits, the results are still conflicting. We investigated two SNPs to find relationships with leptin concentrations. Thirty healthy Caucasian infants younger than 6 months were genotyped for the SNPs G2548A and A19G with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system-mismatch amplification mutation assay (ARMS- MAMA) real-time PCR, and serum leptin concentrations were measured with a radioimmunoassay method. Considering the significant linkage disequilibrium observed between the two SNPs, we divided the sample according to the number of GG haplotypes and observed that individuals homozygous for the GG haplotype had higher serum leptin levels in early infancy than the others. Although these preliminary results are based on a limited sample, they suggest that the genetic background seems to play a role in modulating leptin levels in infancy, but changes in leptin levels over infancy and their correlation with obesity need to be further explored. We describe an ARMS-MAMA real-time PCR procedure which could be profitably applied in routine genetic screening. PMID- 27008408 TI - Inducing Acute Traumatic Coagulopathy In Vitro: The Effects of Activated Protein C on Healthy Human Whole Blood. AB - INTRODUCTION: Acute traumatic coagulopathy has been associated with shock and tissue injury, and may be mediated via activation of the protein C pathway. Patients with acute traumatic coagulopathy have prolonged PT and PTT, and decreased activity of factors V and VIII; they are also hypocoagulable by thromboelastometry (ROTEM) and other viscoelastic assays. To test the etiology of this phenomenon, we hypothesized that such coagulopathy could be induced in vitro in healthy human blood with the addition of activated protein C (aPC). METHODS: Whole blood was collected from 20 healthy human subjects, and was "spiked" with increasing concentrations of purified human aPC (control, 75, 300, 2000 ng/mL). PT/PTT, factor activity assays, and ROTEM were performed on each sample. Mixed effect regression modeling was performed to assess the association of aPC concentration with PT/PTT, factor activity, and ROTEM parameters. RESULTS: In all subjects, increasing concentrations of aPC produced ROTEM tracings consistent with traumatic coagulopathy. ROTEM EXTEM parameters differed significantly by aPC concentration, with stepwise prolongation of clotting time (CT) and clot formation time (CFT), decreased alpha angle (alpha), impaired early clot formation (a10 and a20), and reduced maximum clot firmness (MCF). PT and PTT were significantly prolonged at higher aPC concentrations, with corresponding significant decreases in factor V and VIII activity. CONCLUSION: A phenotype of acute traumatic coagulopathy can be induced in healthy blood by the in vitro addition of aPC alone, as evidenced by viscoelastic measures and confirmed by conventional coagulation assays and factor activity. This may lend further mechanistic insight to the etiology of coagulation abnormalities in trauma, supporting the central role of the protein C pathway. Our findings also represent a model for future investigations in the diagnosis and treatment of acute traumatic coagulopathy. PMID- 27008409 TI - Facing the Heat: Thermoregulation and Behaviour of Lowland Species of a Cold Dwelling Butterfly Genus, Erebia. AB - Understanding the potential of animals to immediately respond to changing temperatures is imperative for predicting the effects of climate change on biodiversity. Ectothermic animals, such as insects, use behavioural thermoregulation to keep their body temperature within suitable limits. It may be particularly important at warm margins of species occurrence, where populations are sensitive to increasing air temperatures. In the field, we studied thermal requirements and behavioural thermoregulation in low-altitude populations of the Satyrinae butterflies Erebia aethiops, E. euryale and E. medusa. We compared the relationship of individual body temperature with air and microhabitat temperatures for the low-altitude Erebia species to our data on seven mountain species, including a high-altitude population of E. euryale, studied in the Alps. We found that the grassland butterfly E. medusa was well adapted to the warm lowland climate and it was active under the highest air temperatures and kept the highest body temperature of all species. Contrarily, the woodland species, E. aethiops and a low-altitude population of E. euryale, kept lower body temperatures and did not search for warm microclimates as much as other species. Furthermore, temperature-dependence of daily activities also differed between the three low-altitude and the mountain species. Lastly, the different responses to ambient temperature between the low- and high-altitude populations of E. euryale suggest possible local adaptations to different climates. We highlight the importance of habitat heterogeneity for long-term species survival, because it is expected to buffer climate change consequences by providing a variety of microclimates, which can be actively explored by adults. Alpine species can take advantage of warm microclimates, while low-altitude grassland species may retreat to colder microhabitats to escape heat, if needed. However, we conclude that lowland populations of woodland species may be more severely threatened by climate warming because of the unavailability of relatively colder microclimates. PMID- 27008410 TI - Increasing the complexity of respiratory syncytial virus infection: Reactive oxygen species, DNA damage, and premature senescence. PMID- 27008415 TI - H19 Functions as a ceRNA in Promoting Metastasis Through Decreasing miR-200s Activity in Osteosarcoma. AB - Osteosarcoma is the most common primary bone sarcoma around the world. The poor prognosis and high recurrence rate of osteosarcoma are largely due to the high rate of pulmonary metastasis. H19 has been reported to play a potential role in osteosarcoma progression. However, the exact molecular mechanism of metastasis involving H19 remains unclear. In the present study, we performed gain- and loss of-function assays and found that H19 promotes migration and invasion in osteosarcoma cells. Furthermore, we showed that H19 promotes metastasis through upregulation of ZEB1 and ZEB2 by competitively binding the miR-200 family. Thus, our findings suggest important roles of H19 in osteosarcoma metastasis and indicate its potential application in osteosarcoma therapy. PMID- 27008416 TI - Effect of the Titanium Nanoparticle on the Quantum Chemical Characterization of the Liquid Sodium Nanofluid. AB - Suspension state of a titanium nanoparticle in the liquid sodium was quantum chemically characterized by comparing physical characteristics, viz., electronic state, viscosity, and surface tension, with those of liquid sodium. The exterior titanium atoms on the topmost facet of the nanoparticle were found to constitute a stable Na-Ti layer, and the Brownian motion of a titanium nanoparticle could be seen in tandem with the surrounding sodium atoms. An electrochemical gradient due to the differences in electronegativity of both titanium and sodium causes electron flow from liquid sodium atoms to a titanium nanoparticle, Ti + Na -> Ti(delta-) + Na(delta+), making the exothermic reaction possible. In other words, the titanium nanoparticle takes a role as electron-reservoir by withdrawing free electrons from sodium atoms and makes liquid sodium electropositive. The remaining electrons in the liquid sodium still make Na-Na bonds and become more stabilized. With increasing size of the titanium nanoparticle, the deeper electrostatic potential, the steeper electric field, and the larger Debye atmosphere are created in the electric double layer shell. Owing to electropositive sodium-to-sodium electrostatic repulsion between the external shells, naked titanium nanoparticles cannot approach each other, thus preventing the agglomeration. PMID- 27008411 TI - microRNAs Regulate Host Immune Response and Pathogenesis During Influenza Infection in Rhesus Macaques. AB - microRNAs (miRNAs) are small noncoding RNAs that are key regulators of biological processes, including the immune response to viral infections. Differential expression levels of cellular miRNAs and their predicted targets have been described in the lungs of H1N1-infected BALB/c mice, the lungs of H5N1 influenza infected cynomolgus macaques, and in peripheral blood mononuclear cells (PBMCs) of critically ill patients infected with 2009 pandemic H1N1. However, a longitudinal analysis of changes in the expression of miRNAs and their targets during influenza infection and how they relate to viral replication and host response has yet to be carried out. In the present study, we conducted a comprehensive analysis of innate and adaptive immune responses as well as the expression of several miRNAs and their validated targets in both peripheral blood and bronchoalveolar lavage (BAL) collected from rhesus macaques over the course of infection with the 2009 H1N1 virus A/Mexico/4108/2009 (MEX4108). We describe a distinct set of differentially expressed miRNAs in BAL and PBMCs, which regulate the expression of genes involved in inflammation, immune response, and regulation of cell cycle and apoptosis. PMID- 27008417 TI - Tracking and Locating Itinerant Subjects With a Rechargeable Incentive Card: Results of a Randomized Trial. AB - BACKGROUND: High attrition among research participants undermines the validity and generalizability of field research. This study contrasted two incentivizing methods--money orders (MOs) or rechargeable incentive cards (RICs)--with regard to rates of participants' study engagement and follow-up contact over a 6-month period. METHODS: Substance abusers (N = 303) in Los Angeles, California were recruited and randomized to either an MO (control) or RIC (experimental) condition. All participants were asked to call the researchers at the beginning of each calendar month for the ensuing 5 months to update their locator information, even if nothing had changed. Each call resulted in a $10 payment, issued immediately via the RIC system or by MO by mail. Research staff located and interviewed all participants at Month 6. Contact logs assessed level of effort required to locate participants and conduct follow-up interviews. RESULTS: Relative to controls, RIC participants, especially those with low ability to defer gratification, initiated more monthly calls. Six-month follow-up rates did not differ between RIC (75%) and controls (79%), though the RIC condition was associated with an average staff time savings of 39.8 minutes per study participant. DISCUSSION: For longitudinal public health research involving itinerant study participants, the RIC method produces a modest benefit in study engagement and reduced staff time devoted to participant tracking and payments. However, the overall cost-effectiveness of this approach will depend on the pricing model of the card-issuing vendor (which in turns depends on the scale of the project, with per-unit costs falling for larger projects). PMID- 27008418 TI - Harnessing group composition-related effects in pain management programs: a review and recommendations. AB - Cognitive-behavioral therapy, an effective management strategy for chronic pain, is frequently conducted in groups. Although clinicians often report 'knowing when a group will go well or badly', investigations of the effect that group composition might have on outcomes is lacking. Conceptual models, explanatory theories and experiments have been developed in fields of psychotherapy, organizational, social and educational psychology, but there has been no attempt to take on this issue in our field. The current hypothesis-generating review synthesizes these substantial bodies of literature to identify common themes across fields and integrate them with current concepts of cognitive-behavioral therapy-based pain management. We present a putative conceptual model with testable hypotheses relating to features of each group as a whole, the individuals in that group and the group's leader. PMID- 27008419 TI - Evolutionary Conserved Positions Define Protein Conformational Diversity. AB - Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like beta-sheets and alpha-helix. PMID- 27008422 TI - Varying Patterns on Varying Scales: A Metacommunity Analysis of Nematodes in European Lakes. AB - Ecological community patterns are often extremely complex and the factors with the greatest influence on community structure have yet to be identified. In this study we used the elements of metacommunity structure (EMS) framework to characterize the metacommunities of freshwater nematodes in 16 European lakes at four geographical scales (radius ranging from 80 m to 360 km). The site characteristics associated with site scores indicative of the structuring gradient were identified using Spearman rank correlations. The metacommunities of the 174 nematode species included in this analysis mostly had a coherent pattern. The degree of turnover increased with increasing scale. Ordination scores correlated with geographical variables on the larger scales and with the trophic state index on a regional scale. The association of the structuring gradient with spatial variables and the scale-dependent increase in turnover showed that nematode dispersal was limited. The different metacommunity patterns identified at the increasing geographical scales suggested different, scale-related mechanisms of species distribution, with species sorting dominating on smaller and mass effects on larger geographical scales. PMID- 27008420 TI - Synthetic Cyclolipopeptides Selective against Microbial, Plant and Animal Cell Targets by Incorporation of D-Amino Acids or Histidine. AB - Cyclolipopeptides derived from the antimicrobial peptide c(Lys-Lys-Leu-Lys-Lys Phe-Lys-Lys-Leu-Gln) (BPC194) were prepared on solid-phase and screened against four plant pathogens. The incorporation at Lys5 of fatty acids of 4 to 9 carbon atoms led to active cyclolipopeptides. The influence on the antimicrobial activity of the Lys residue that is derivatized was also evaluated. In general, acylation of Lys1, Lys2 or Lys5 rendered the sequences with the highest activity. Incorporation of a D-amino acid maintained the antimicrobial activity while significantly reduced the hemolysis. Replacement of Phe with a His also yielded cyclolipopeptides with low hemolytic activity. Derivatives exhibiting low phytotoxicity in tobacco leaves were also found. Interestingly, sequences with or without significant activity against phytopathogenic bacteria and fungi, but with differential hemolysis and phytotoxicity were identified. Therefore, this study represents an approach to the development of bioactive peptides with selective activity against microbial, plant and animal cell targets. These selective cyclolipopeptides are candidates useful not only to combat plant pathogens but also to be applied in other fields. PMID- 27008421 TI - Prioritising Mangrove Ecosystem Services Results in Spatially Variable Management Priorities. AB - Incorporating the values of the services that ecosystems provide into decision making is becoming increasingly common in nature conservation and resource management policies, both locally and globally. Yet with limited funds for conservation of threatened species and ecosystems there is a desire to identify priority areas where investment efficiently conserves multiple ecosystem services. We mapped four mangrove ecosystems services (coastal protection, fisheries, biodiversity, and carbon storage) across Fiji. Using a cost effectiveness analysis, we prioritised mangrove areas for each service, where the effectiveness was a function of the benefits provided to the local communities, and the costs were associated with restricting specific uses of mangroves. We demonstrate that, although priority mangrove areas (top 20%) for each service can be managed at relatively low opportunity costs (ranging from 4.5 to 11.3% of overall opportunity costs), prioritising for a single service yields relatively low co-benefits due to limited geographical overlap with priority areas for other services. None-the-less, prioritisation of mangrove areas provides greater overlap of benefits than if sites were selected randomly for most ecosystem services. We discuss deficiencies in the mapping of ecosystems services in data poor regions and how this may impact upon the equity of managing mangroves for particular services across the urban-rural divide in developing countries. Finally we discuss how our maps may aid decision-makers to direct funding for mangrove management from various sources to localities that best meet funding objectives, as well as how this knowledge can aid in creating a national mangrove zoning scheme. PMID- 27008423 TI - Tulbaghia--A Southern African Phytomedicine. AB - The phytomedicine Tulbaghia consists of the fresh or dried subterranean organs of various Tulbaghia species. The genus is endemic to Southern Africa and includes about 20 species, of which only T. alliacea and T. capensis are naturally found in the winter rainfall climate area (the Western Cape). The genus forms part of the Alliaceae family and is a geophyte (plants with an underground perennation organ and leaves that die back annually). Their habitat can range from semi desert to wet and boggy terrain. Wild garlic is most commonly prepared as an infusion or boiled in water and taken orally. Externally, as a medicated bath, wild garlic is used to treat paralysis and rheumatism and to reduce the temperature in a feverish patient. Internally, rhizome or bulb preparations are taken orally to treat fever; as a remedy for colds and influenza, asthma, tuberculosis, and stomach problems; as an antihypertensive; or to expel intestinal worms. It is also used as a prophylactic against winter infections. Rhizome pieces are often placed in castor oil to make eardrops. For fever and high blood pressure, a tea is made from the bulbs or rhizomes and a small cup taken three times daily. The leaves of the plant are used to treat esophageal cancer and may also be eaten as a vegetable. The demand for Tulbaghia in both formal and informal markets has grown exponentially. Sustainable harvesting focuses on only harvesting enough of the plant so that it still has the capacity for self-renewal. However, because both the above-ground and underground parts of Tulbaghia are commonly used in African traditional medicine, destructive harvesting of the whole plant is inevitable, thus necessitating the large-scale organized propagation of these plants. It is therefore important to establish a new strategy for the sustainable harvesting of these plants as commercial crops. PMID- 27008424 TI - An Atypical Case of Lymphocytic Panhypophysitis in a Pregnant Woman. AB - We describe a case of lymphocytic panhypophysitis (LPH) in a 30-year-old woman presenting with throbbing headaches and vision changes during her third trimester. LPH is the rarest subclassification of lymphocytic hypophysitis; it is typically found in males and has not previously been associated with pregnancy. Anterior and posterior pituitary deficits together with headaches should raise a high degree of suspicion regarding the possibility of LPH. The atypical magnetic resonance imaging finding of a heterogeneous pituitary mass additionally raised concern about pituitary apoplexy. Tissue from a transsphenoidal biopsy permitted diagnosis of lymphocytic hypophysitis. There was infiltration of the pituitary gland by small B and T lymphocytes. Resolution of the visual symptoms occurred after the biopsy and treatment with intravenous steroids. PMID- 27008426 TI - Modeling Polymorphic Molecular Crystals with Electronic Structure Theory. AB - Interest in molecular crystals has grown thanks to their relevance to pharmaceuticals, organic semiconductor materials, foods, and many other applications. Electronic structure methods have become an increasingly important tool for modeling molecular crystals and polymorphism. This article reviews electronic structure techniques used to model molecular crystals, including periodic density functional theory, periodic second-order Moller-Plesset perturbation theory, fragment-based electronic structure methods, and diffusion Monte Carlo. It also discusses the use of these models for predicting a variety of crystal properties that are relevant to the study of polymorphism, including lattice energies, structures, crystal structure prediction, polymorphism, phase diagrams, vibrational spectroscopies, and nuclear magnetic resonance spectroscopy. Finally, tools for analyzing crystal structures and intermolecular interactions are briefly discussed. PMID- 27008425 TI - Effect of Foot-and-Mouth Disease Virus Infection on the Frequency, Phenotype and Function of Circulating Dendritic Cells in Cattle. AB - Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms develop within 2 to 3 days of exposure and include fever and vesicular lesions on the tongue and hooves. Dendritic cells (DC) play an essential role in protective immune responses against pathogens. Therefore, investigating their role during FMDV infection would lead to a better understanding of host-pathogen interactions. In this study, following infection of cattle with FMDV, we investigated the frequency and function of conventional (cDC) and plasmacytoid DC (pDC) in blood by using multi-color flow cytometry. We show that the frequency of cDC and pDC increased following FMDV infection and peaked 3 to 4 days post infection. During peak viremia, the cattle became lymphopenic, the expression of MHC class II molecules on cDC and pDC was dramatically down-regulated, the processing of exogenous antigen by cDC and pDC was impaired, and there was an increase in IL-10 production by DC and monocytes. Notably, after clearance of FMDV from the blood, MHC class II expression returned to pre-infection levels. Altogether, our study demonstrates that in cattle, FMDV inhibits the function of DC, thereby retarding the initiation of adaptive immune responses, potentially enhancing virus shedding during the acute phase of infection. PMID- 27008427 TI - Effects of Corticosterone on Immune Functions of Cultured Rat Splenic Lymphocytes Exposed to Aluminum Trichloride. AB - Aluminum (Al) exposure is toxic to immune system. Studies have implicated that glucocorticoids (GCs) exert the dual regulation effect on the immune function depending on the concentration. However, it is unknown whether a dual effect of GCs exists in the AlCl3-treated lymphocytes. Corticosterone (Cort) is one kind of GCs. To investigate the effect of different concentration Cort on AlCl3-treated lymphocytes, rat splenic lymphocyte was isolated and cultured with 0.55 mmol/L AlCl3, simultaneously administrated Cort at final concentration of 0 (control group, CG), 10(-8) (low-level group, LG), and 10(-6) (high-level group, HG) mol/L, respectively. Another group without AlCl3 and Cort served as the blank group (BG). We found that low concentration Cort increased the T and B lymphocyte proliferation rate, proportions of CD4(+) T lymphocyte subset, IgG, IL-2, and TNF alpha contents, whereas high concentration Cort decreased those in AlCl3-treated lymphocytes. In conclusion, the results of this study indicated that low concentration Cort relieves the immunotoxicity of AlCl3 on the splenic lymphocytes, whereas high concentration Cort aggravates it. PMID- 27008428 TI - Toxic Effects of Titanium Dioxide Nanoparticles and Titanium Dioxide Bulk Salt in the Liver and Blood of Male Sprague-Dawley Rats Assessed by Different Assays. AB - This study evaluated the toxic effects of titanium dioxide (TiO2) bulk salt as well as its nanoparticles (NPs) in anatase phase with mean crystallite size of 36.15 nm in male Sprague-Dawley rats by subcutaneous injections at four different dose levels of either control (0), 50, 100 or 150 mg/kg of body weight (BW) of rat for 28 days on alternate days. Animal mortality, haematology, micronucleus assay, liver histology and activities of liver tissue damage markers like, alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), as well as oxidative stress indicators like superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) were investigated. The study revealed significant differences (P < 0.05) among control and experimental groups in all the haematological parameters at the end of experiment. Significantly elevated levels (P < 0.05) of ALT, AST and ALP were found for the group treated with TiO2 NPs at the dose of 150 mg/kg of body weight as compared to control. TiO2 and TiO2 NPs caused dose-dependent genotoxicity in the blood cells of the treated rat as revealed by micronuclei test. The highest frequency of micronuclei was observed in rats treated with NPs at the dose of 150 mg/kg BW which was significantly different (P < 0.001) from all other experimental groups after 28 days of exposure. Similarly, all the treatments showed dose-dependent oxidative stress in the treated rats. However, the significantly high decline in the activities of CAT, SOD, and GST as well as elevation in malondialdehyde and GSH was observed in the group receiving NPs at the rate of 150 mg/kg BW. TiO2 also caused histological alterations in the liver. The study revealed that higher dose of TiO2 NPs exerted significantly harmful effects on liver and blood as compared to its lower doses as well as from all other doses of their bulk counterparts. PMID- 27008429 TI - Anti-inflammatory Effect of Mesenchymal Stromal Cell Transplantation and Quercetin Treatment in a Rat Model of Experimental Cerebral Ischemia. AB - Here, we have investigated the synergistic effect of quercetin administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following middle cerebral artery occlusion in rat. Combining quercetin treatment with delayed transplantation of HUMSCs after local cerebral ischemia significantly (i) improved neurological functional recovery; (ii) reduced proinflammatory cytokines (interleukin(IL)-1beta and IL-6), increased anti inflammatory cytokines (IL-4, IL-10, and transforming growth factor-beta1), and reduced ED-1 positive areas; (iii) inhibited cell apoptosis (caspase-3 expression); and (iv) improved the survival rate of HUMSCs in the injury site. Altogether, our results demonstrate that combined HUMSC transplantation and quercetin treatment is a potential strategy for reducing secondary damage and promoting functional recovery following cerebral ischemia. PMID- 27008430 TI - The prognostic value of rectal invasion for stage IVA uterine cervical cancer treated with radiation therapy. AB - BACKGROUND: The prognostic value of rectal invasion is still unclear in stage IVA cervical cancer. The objective of this study is to evaluate patient outcome and prognostic factors in stage IVA cervical cancer treated with radiation therapy. METHODS: A retrospective review of the medical records of patients treated with definitive photon radiation therapy for pathologically proven stage IVA cervical cancer between 1980 and 2010 was performed. Eligible patients for the present study were diagnosed with clinical stage IVA cervical cancer by cystoscopy or/and proctoscopy, and they received definitive radiation therapy consisting of a combination of external beam radiotherapy and high-dose-rate brachytherapy. All patients underwent CT scans of the abdomen and pelvis. RESULTS: Among the 67 stage IVA patients studied, 53 patients were stage IVA on the basis of bladder invasion, 7 according to rectal mucosal invasion, and 7 because of both bladder and rectal mucosal invasion. Median follow-up of all patients and surviving patients was 19 months (range, 2-235 months) and 114 months (range, 14-223 months), respectively. The 5-year local control (LC), disease-free survival (DFS), and overall survival (OS) rate were 55, 17, and 24%, respectively. Rectal invasion had significant impact on DFS, but bladder invasion had the opposite effect (p = 0.00006 and 0.005, respectively). There were significant differences of LC, DFS and OS rates between patients with and without rectal invasion (p = 0.006, 0.00006 and 0.05, respectively). CONCLUSIONS: Patients with stage IVA cervical cancer had poor prognosis, with 5-year survival of only 24%. Furthermore, in stage IVA, rectal invasion might be a worse prognostic factor than bladder invasion. PMID- 27008431 TI - Variability and bias assessment in breast ADC measurement across multiple systems. AB - PURPOSE: To assess the ability of a recent, anatomically designed breast phantom incorporating T1 and diffusion elements to serve as a quality control device for quantitative comparison of apparent diffusion coefficient (ADC) measurements calculated from diffusion-weighted MRI (DWI) within and across MRI systems. MATERIALS AND METHODS: A bilateral breast phantom incorporating multiple T1 and diffusion tissue mimics and a geometric distortion array was imaged with DWI on 1.5 Tesla (T) and 3.0T scanners from two different manufacturers, using three different breast coils (three configurations total). Multiple measurements were acquired to assess the bias and variability of different diffusion weighted single-shot echo-planar imaging sequences on the scanner-coil systems. RESULTS: The repeatability of ADC measurements was mixed: the standard deviation relative to baseline across scanner-coil-sequences ranged from low variability (0.47, 95% confidence interval [CI]: 0.22-1.00) to high variability (1.69, 95% CI: 0.17 17.26), depending on material, with the lowest and highest variability from the same scanner-coil-sequence. Assessment of image distortion showed that right/left measurements of the geometric distortion array were 1 to 16% larger on the left coil side compared with the right coil side independent of scanner-coil systems, diffusion weighting, and phase-encoding direction. CONCLUSION: This breast phantom can be used to measure scanner-coil-sequence bias and variability for DWI. When establishing a multisystem study, this breast phantom may be used to minimize protocol differences (e.g., due to available sequences or shimming technique), to correct for bias that cannot be minimized, and to weigh results from each system depending on respective variability. J. Magn. Reson. Imaging 2016. J. MAGN. RESON. IMAGING 2016;44:846-855. PMID- 27008432 TI - Peer-assisted learning in a student-run free clinic project increases clinical competence. AB - BACKGROUND: Germany's first student-run free clinic (SRFC) for medically underserved patients has been established at the medical faculty of the Goethe University, Frankfurt/Germany. Participating students are educated in a Peer Assisted Learning program (PAL). Little is known about the effectiveness of PAL in SRFCs. METHODS: We conducted a randomized, controlled, prospective study involving 50 participants. Students were either tested before or after receiving PAL. Knowledge and skill level were measured by theoretical and practical tests. In addition, curricular Objective Structured Clinical Examination (OSCE) results were compared between the groups. RESULTS: Students receiving PAL had significantly better results in theoretical (p < 0.001) and practical (p < 0.001) tests, as well as in the OSCE (p < 0.01). A control test showed no significant difference (p = 0.205) indicating similar prerequisites between the groups. CONCLUSION: Improved results of the study group indicate an increase in the clinical knowledge and skills. PAL appears to be suitable for the training of basic medical skills and family medicine related knowledge and similar teaching projects could be based on it at other SRFCs. PMID- 27008434 TI - [Current Aspects on the Pathogenesis of Urinary Tract Infections]. AB - Urinary tract infections are among the most common bacterial infectious diseases worldwide. Every second woman will experience at least one urinary tract infection in her lifetime. The administration of antibiotics has been a safe and efficient treatment modality so far. However, due to the emergence of multi resistant pathogens and the developmental void of new antimicrobial drugs, the therapy of infections mighty become more challenging in the near future. So, knowledge of the complex host-pathogen interaction is of great importance. Common phenotypes observed in clinical practice suggest basic principles, which are relevant for the development of novel antimicrobial strategies. With invading pathogens forming intracellular bacterial communities they evade host response and provide a nidus for recurrent infection. A plethora of virulence factors allow uropathogenic bacteria to colonize and to establish infections in the urinary tract. In response, host responses seem to address specific virulence mechanisms that are essential to pathogenicity. Deciphering the molecular mechanisms underlying the complex host-pathogen interaction is critical to devise novel treatment options. PMID- 27008433 TI - Fusariosis in a Patient with Acute Myeloid Leukemia: A Case Report and Review of the Literature. AB - Fusarium spp. causes infections mostly in patients with prolonged neutropenia. We describe the case of a disseminated Fusarium solani infection in a patient with acute myeloid leukemia which never reached complete remission during its clinical course. The patient had profound neutropenia and developed skin nodules and pneumonia in spite of posaconazole prophylaxis. F. solani was isolated from blood and skin biopsy, being identified from its morphology and by molecular methods. By broth dilution method, the strain was resistant to azoles, including voriconazole and posaconazole, and to echinocandins. MIC to amphotericin B was 4 mg/L. The patient initially seemed to benefit from therapy with voriconazole and amphotericin B, but, neutropenia perduring, his clinical condition deteriorated with fatal outcome. All efforts should be made to determine the correct diagnosis as soon as possible in a neutropenic patient and to treat this infection in a timely way, assuming pathogen susceptibility while tests of antimicrobial susceptibility are pending. A review of the most recent literature on invasive fungal infections is reported. PMID- 27008435 TI - Low-Temperature H2S Detection with Hierarchical Cr-Doped WO3 Microspheres. AB - Hierarchical Cr-doped WO3 microspheres have been successfully synthesized for efficient sensing of H2S gas at low temperatures. The hierarchical structures provide an effective gas diffusion path via well-aligned micro-, meso-, and macroporous architectures, resulting in significant enhancement in sensing response to H2S. The temperature and gas concentration dependence on the sensing properties elucidate that Cr dopants remarkably improve the response and lower the sensor' operating temperature down to 80 degrees C. Under 0.1 vol % H2S, the response of Cr-doped WO3 sensor is 6 times larger than pristine WO3 sensor at 80 degrees C. We suggest the increasing number of oxygen vacancies created by Cr dopants to be the underlying reason for enhancement of charge carrier density and accelerated reactions with H2S. PMID- 27008436 TI - SnS 3D Flowers with Superb Kinetic Properties for Anodic Use in Next-Generation Sodium Rechargeable Batteries. AB - Tin sulfide (SnS) 3D flowers containing hierarchical nanosheet subunits are synthesized using a simple polyol process. The Li ion cells incorporating SnS 3D flowers exhibit an excellent rate capability, as well as good cycling stability, compared to SnS bulks and Sn nanoparticles. These desirable properties can be attributed to their unique morphology having not only large surface reaction area but also enough space between individual 2D nanosheets, which alleviates the pulverization of SnS. PMID- 27008437 TI - QSAR modeling and molecular interaction analysis of natural compounds as potent neuraminidase inhibitors. AB - Different QSAR models of 40 natural compounds as neuraminidase inhibitors (NIs) are developed to comprehend chemical-biological interactions and predict activities against neuraminidase (NA) from Clostridium perfringens. Based on the constitutional, topological and conformational descriptors, R(2) and Q(2) values of the obtained SRA model are 0.931 and 0.856. The R(2) and Q(2) values of the constructed HQSAR and almond models are 0.903 and 0.767, 0.904 and 0.511, respectively. Based on the pharmacophore alignment, R(2) and Q(2) values of the optimal CoMSIA model are 0.936 and 0.654. Moreover, Rtest(2) and Qext(2) of values of SRA, HQSAR, almond and CoMSIA models are 0.611 and 0.565, 0.753 and 0.750, 0.612 and 0.582, 0.582 and 0.571, respectively. So, QSAR models have good predictive capability. They can be further used to evaluate and screen new compounds. Moreover, hydrogen bonds and electrostatic factors have high contributions to activities. To understand molecular interactions between natural compounds and NA from Clostridium perfringens, molecular docking is investigated. The docking results elucidate that Arg266, Asp291, Asp328, Tyr485, Glu493, Arg555, Arg615 and Tyr655 are especially the key residues in the active site of 2bf6. Hydrogen bonds and electrostatics are key factors, which impact the interactions between NIs and NA. So, the influential factors of interactions between NIs and NA in the docking results are in agreement with the QSAR results. PMID- 27008438 TI - An Ancestral Tryptophanyl-tRNA Synthetase Precursor Achieves High Catalytic Rate Enhancement without Ordered Ground-State Tertiary Structures. AB - Urzymes-short, active core modules derived from enzyme superfamilies-prepared from the two aminoacyl-tRNA synthetase (aaRS) classes contain only the modules shared by all related family members. They have been described as models for ancestral forms. Understanding them currently depends on inferences drawn from the crystal structures of the full-length enzymes. As aaRS Urzymes lack much of the mass of modern aaRS's, retaining only a small portion of the hydrophobic cores of the full-length enzymes, it is desirable to characterize their structures. We report preliminary characterization of (15)N tryptophanyl-tRNA synthetase Urzyme by heteronuclear single quantum coherence (HSQC) NMR spectroscopy supplemented by circular dichroism, thermal melting, and induced fluorescence of bound dye. The limited dispersion of (1)H chemical shifts (0.5 ppm) is inconsistent with a narrow ensemble of well-packed structures in either free or substrate-bound forms, although the number of resonances from the bound state increases, indicating a modest, ligand-dependent gain in structure. Circular dichroism spectroscopy shows the presence of helices and evidence of cold denaturation, and all ligation states induce Sypro Orange fluorescence at ambient temperatures. Although the term "molten globule" is difficult to define precisely, these characteristics are consistent with most such definitions. Active-site titration shows that a majority of molecules retain ~60% of the transition state stabilization free energy observed in modern synthetases. In contrast to the conventional view that enzymes require stable tertiary structures, we conclude that a highly flexible ground-state ensemble can nevertheless bind tightly to the transition state for amino acid activation. PMID- 27008439 TI - Factors affecting cashew processing by wild bearded capuchin monkeys (Sapajus libidinosus, Kerr 1792). AB - Cashew nuts are very nutritious but so well defended by caustic chemicals that very few species eat them. We investigated how wild bearded capuchin monkeys (Sapajus libidinosus) living at Fazenda Boa Vista (FBV; Piaui, Brazil) process cashew nuts (Anacardium spp.) to avoid the caustic chemicals contained in the seed mesocarp. We recorded the behavior of 23 individuals toward fresh (N = 1282) and dry (N = 477) cashew nuts. Adult capuchins used different sets of behaviors to process nuts: rubbing for fresh nuts and tool use for dry nuts. Moreover, adults succeed to open dry nuts both by using teeth and tools. Age and body mass significantly affected success. Signs of discomfort (e.g., chemical burns, drooling) were rare. Young capuchins do not frequently closely observe adults processing cashew nuts, nor eat bits of nut processed by others. Thus, observing the behavior of skillful group members does not seem important for learning how to process cashew nuts, although being together with group members eating cashews is likely to facilitate interest toward nuts and their inclusion into the diet. These findings differ from those obtained when capuchins crack palm nuts, where observations of others cracking nuts and encounters with the artifacts of cracking produced by others are common and support young individuals' persistent practice at cracking. Cashew nut processing by capuchins in FBV appears to differ from that observed in a conspecific population living 320 km apart, where capuchins use tools to open both fresh and dry nuts. Moreover, in the latter population, chemical burns due to cashew caustic compounds appear to be common. The sources of these differences across populations deserve investigation, especially given that social influences on young monkeys learning to open cashew nuts at FBV seem to be nonspecific. Am. J. Primatol. 78:799-815, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27008440 TI - An Evolving Insight into Chiral H-Bond Catalyzed Aza-Henry Reactions: A Cooperative Role for Noncovalent Attractive Interactions Unveiled by Density Functional Theory. AB - The role of cooperative effects arising from noncovalent attractive interactions as a vital factor governing stereoinduction in chiral H-bond catalyzed aza-Henry reactions is reported. Supporting this finding were density functional theory (DFT) calculations which revealed a shape and size dependency existed between the catalyst and substrates that when matched lead to high enantioselectivity, as reflected by favorable activation parameters. Associated with optimal catalyst and substrate pairing were a closed catalytic binding pocket and a synclinal orientation of the substrates that reinforced favorable stereoelectronic effects and dispersive type forces. Meanwhile, unfavorable steric interactions were found to be a dominant effect controlling diastereoselection. PMID- 27008441 TI - [Gout]. PMID- 27008442 TI - [Gout management: an update]. AB - Gout is the most frequent arthritis worldwide. Despite progress in therapeutic options the majority of gout patients are still insufficiently treated. International guidelines (ACR, EULAR, 3e initiative) clearly specify treatment targets: keep the patient flare-free and maintain a low urate serum level (< 360 umol/l). The treat to target strategy includes therapy of flares, urate lowering treatment (ULT) and prophylaxis of flares. Evolution of gout guidelines over several years shows a broader indication for ULT, mandatory prophylaxis of flares during the initiation of ULT over several months and an earlier start of ULT in patients with flares as soon as symptoms have diminished. Colchicine is the preferred specific flare treatment, Caution has to be taken especially in patients with kidney disease, patients with hepatic dysfunction or in patients with interacting comedication. Low dose oral colchicine is nowadays the standard flare treatment. NSAIDs and prednisone are valuable alternatives. Interleukin-1 blockers offer a quick resolution of flares and may be an option in patients with chronic gout and severe kidney disease. Xanthinoxidase inhibitors (XOI) are the mainstay of ULT, with allopurinol still being the preferred XOI. The recently approved XOI febuxostat is eliminated mostly by the liver and can induce a faster lowering of urate. Uricosuric drugs such as probenecid are recommended in patients with sufficient renal function in whom the treatment goals cannot be reached with XOI. In Switzerland, only the two gout-lowering drugs allopurinol and probenecid are available, which reduces the therapeutic possibilities. Treatment success is often hampered by malcompliance. Recent guidelines stress the importance of patient education to ameliorate compliance. Comorbidities such as metabolic syndrome, cardiovascular and kidney disease are often found in gout patients. Patients with severe kidney disease are the most difficult to treat: the choice of antiinflammatory treatment is narrowed, ULT has to be uptitrated very carefully and patients often suffer from repeated flares. Another factor associated with treatment failure is the low physician's adherence towards the guidelines. Therapeutic failure can lead to chronic and refractory gout (polyarticular gout, uncontrolled flare activity, chronic synovitis, destructive tophi) which makes the further management very difficult. Most gout patients are treated in primary care settings. Patients with chronic gout or at high risk for development of chronic gout (in particular patients with severe kidney disease or patients transplanted) should be additionally treated by a rheumatologist. PMID- 27008443 TI - [Current epidemiology of gout]. AB - Gout is the most common inflammatory arthritis in adults nowadays. Prevalence has risen over the last decades. Patients over 65 years are disproportionally affected. A male/female ratio of 4:1 is diminishing after menopause (still 3:1). The relative risk of developing gout increases in a linear progression with the serum uric acid level. Other risk factors beside hyperuricemia are genetic predisposition, age, male gender, adipositas, lifestyle modification, chronic kidney disease and intake of diuretics. Many gout patients suffer from comorbidities. The metabolic syndrome is associated with gout. Two fifths of patients with gout had also chronic kidney disease. Reasons for the rise in prevalence are longevity, dietary habits and the high prevalence of patients with chronic kidney disease in the general population. PMID- 27008444 TI - [Imaging findings of cristal deposit disorders]. AB - Cristal deposit disorders are characterised by cristal deposits in hyaline and fibrocartilage, in synovium, capsule, ligaments and tendons and periarticular soft tissue. Calciumpyrophosphatedihydrate (CPPD), hydroxyapatite (calcific tendinitis) and uric acid arthropathies are the most common cristal deposit diseases. Radiography is still the number one image modality for initial imaging and the identification of cristal-induced inflammatory arthropathies. Differentiation between the entities of cristal deposit arthropathies can be challenging. Clincial and radiological findings may overlap in different cristal deposit arthropathies, owing a certain diagnosis difficult. PMID- 27008445 TI - [Histopathophysiology of Gout]. AB - Despite being a frequent cause of arthritis and bone erosions, the underlying cellular and subcellular reaction in gout is insufficiently understood. The inflammasome as intracellular sensor for crystals plays an important role, notably resulting in interleukin (IL)-1 production. Morphologically, hyperplasia of the synovial membrane with joint effusion, along with fibrinogen deposition and influx of neutrophils and lymphocytes are observed. Extracellular NET formation by neutrophils is involved in the regulation of inflammatory tissue reaction. Furthermore, the release of IL-10 and tumor necrosis factor (TNF) receptors along with lymphocyte proliferation induce the natural resolution of acute gouty arthritis which typically occurs after several days. In contrast to acute gout, tophi consisting of urate crystals are surrounded by histiocytes and multinucleated cells, resembling a foreign body reaction. The deposition of extracellular matrix by fibrocytes is usually observed around tophi. This fibrotic reaction is likely enhanced by Th2-lymphocytes. Bone erosions in gout occur around tophi and are triggered by osteoclast activation through RANK-ligand expression by lymphocytes. In conclusion, understanding the orchestration of inflammation in gout might help to identify new therapeutic targets. PMID- 27008446 TI - [Hyperuricemia, gout and cardiovascular diseases]. AB - Hyperuricemia, gout as well as arterial hypertension and metabolic syndrom are highly prevalent and clinicians are frequently confronted with both conditions in the same patient. Hyperuricemia and gout are associated with cardiovascular comorbidities and a high cardiovascular risk. Despite coherent pathophysiological concepts, it remains to be determined, if this association is independent and causal. In daily clinical practice, cardiovascular risk factors should be thoroughly identified and consequently treated in all patients with hyperuricemia and gout. If preventive treatment of asymptomatic hyperuricemia with urate lowering agents may improve cardiovascular risk and outcomes remains to be determined and is recommended only in special situations like young patients with severe hyperuricemia. PMID- 27008447 TI - [Causes, mechanisms and possible therapeutic targets of gout]. AB - Gout is the most frequent arthritis worldwide with increasing prevalence in industrialized countries and massive socioeconomic consequences. The knowledge regarding the pathomechanisms which lead to arthritis has substantially increased during the last decade. Consistently, new therapeutic approaches and substances appear at the horizon. This review covers aspects of clinical presentation, diagnosis and current treatment. The pathomechanisms leading to NLRP3 inflammasome activation and IL-1beta secretion are reviewed in detail. Finally, selected new therapeutic targets and substances are discussed. PMID- 27008448 TI - [Nutritional therapy of gout]. AB - Nutrition and nutritional behaviours have been found to play a major role in the development of gout. Studies show that body mass index (BMI), as well as excessive intake of alcoholic beverages, meat, soft drinks and fruit juices increase the risk of developing gout. Similarly, dairy products and coffee have been seen to decrease the risk of hyperuricemia and gout, as they increase the excretion of uric acid. Flares of gout are often caused by large meals and high alcohol consumption. Each additional intake of meat portion per day increases the risk of gout by 21 %. Taking total alcohol consumption into account, the risk of gout increases after one to two standard drinks. In contrast to previous assumptions purine-rich plant foods like legumes and vegetables do not increase the risk of gout. The current dietary guidelines take into account nutritional factors, which not only consider purine intake, but also their endogenous production and their influence on renal excretion. A balanced diet based on the Swiss healthy eating guideline pyramid as well as the Mediterranean diet is appropriate for this patient population. The treatment of gout is multi-faceted, since this patient population presents other comorbidities such as obesity, diabetes mellitus, dyslipidemia and hypertension. Collectively, these risk factors are diet dependent and require a treatment strategy that is centered on modifying one's nutrition and nutritional behaviours. The aim of such therapy is to educate the patient as well as treat the accompanying comorbidities with the goal of decreasing serum uric acid values. Motivated patients require consultation and follow-up care in order to be able to actively decrease the serum uric acid. PMID- 27008449 TI - [Uric acid, kidney disease and nephrolithiasis]. AB - Different types of kidney disease are known to be associated with hyperuricemia. The underlying pathophysiologic mechanisms strongly vary, and different ways of therapeutic approach are therefore required. In tumor lysis syndrome, a rapid, excessive increase of serum uric acid level can cause an acute renal failure. For chronic urate nephropathy, on the other hand, constantly elevated serum uric acid level for a longer period seems to be important. Being still controversial as a disease entity however, the aetiology for putative chronic urate nephropathy might be in fact chronic lead intoxication, as suggested by quite an amount of association data. In terms of uric acid nephrolithiasis, the major risk factor is a urinary acidification defect with persistently acidic urine pH, and not necessarily hyperuricemia or hyperuricosuria. Evidence suggests that metabolic diseases with increased insulin resistance are strongly associated with urinary acidification defect. Patients with uric acid kidney stones should therefore be thoroughly evaluated for such metabolic diseases and in a positive case adequately treated. PMID- 27008450 TI - [Uric acid and kidneys - Physiological and pathophysiological aspects]. AB - Kidneys play a critical role in the excretion of uric acid. Improved knowledge of the renal tubular uric acid transport mechanisms helps to better understand, why hyper- or hypouricemia can develop without the external influence of purine intake. Besides the genetic mutations, several drugs and specific medical conditions can significantly influence the tubular excretion of uric acid and thus the serum uric acid level. It seems evident that the renal function per se has a relevant impact on the uric acid excretion. It is however not clear, whether uric acid has a causal role in the development of chronic kidney disease and if so, to what extent. In order to better understand the impact of hyper- and hypouricemia and especially their clinical relevance, further researches on the renal tubular physio- and pathophysiology and also high quality intervention studies are required. PMID- 27008451 TI - Reconstitution of the RNA-dependent RNA polymerase activity of Antheraea mylitta cypovirus in vitro using separately expressed different functional domains of the enzyme. AB - Antheraea mylitta cytoplasmic polyhedrosis virus is a segmented dsRNA virus of the family Reoviridae. Segment 2 (S2)-encoded RNA-dependent RNA polymerase (RdRp) helps the virus to propagate its genome in the host cell of the silkworm, Antheraea mylitta. Cloning, expression, purification and functional analysis of individual domains of RdRp have demonstrated that the purified domains interact in vitro. The central polymerase domain (PD) shows nucleotide binding properties, but neither the N-terminal domain (NTD) nor the C-terminal domain (CTD). Isolated PD does not exhibit RdRp activity but this activity can be reconstituted when all three domains are included in the reaction mixture. Molecular dynamics simulation suggests that the isolated PD has increased internal motions in comparison to when it is associated with the NTD and CTD. The motions of the separated PD may lead to the formation of a less accessible RNA template-binding channel and, thus, impair RdRp activity. PMID- 27008452 TI - Correction to Human and Bovine Viruses and Bacteria at Three Great Lakes Beaches: Environmental Variable Associations and Health Risk. PMID- 27008453 TI - Extensive basal ganglia hematomas treated by local thrombolysis versus conservative management - a comparative retrospective analysis. AB - OBJECTIVES: Single-target puncture plus catheter insertion into the clot is a routine step in hematoma aspiration and local thrombolysis for spontaneous intracerebral haemorrhage (ICH). However, multiple-target puncture of this procedure may imply faster hematoma reduction for large-area ICH. We retrospectively examined the outcomes after clot aspiration plus local thrombolysis with single-/double-target and conservative therapy for extensive basal ganglic hematomas. METHODS: A case note review was conducted on a consecutive series of ICH patients in a single centre with huge basal ganglia hematomas who underwent clots aspiration and thrombolysis or pure medical therapy. We analysed the clinical presentation, radiological features and treatment outcomes of ICH patients in single-target group, double-target group and conservative group. RESULTS: A total of 92 ICH cases were included in this study. At the post-treatment assessment, the average level by hematoma size in single-target and double-group was respectively smaller than that in the conservative group (20.61 ml vs. 15.75 ml vs 60.53 ml, p < 0.01). The 30-day case fatality rate in conservative group was respectively significantly higher than that in single-target and double-target groups (50% vs. 14.70% vs. 20.59%, p < 0.01). At the time of 6-month follow-up, the proportion of good survival in conservative group was respectively remarkably less than that in single- and double-target group (29.17% vs.64.71% vs. 67.65%, p < 0.01). But no difference was detected with respect to 30-day mortality or long-time outcome between the two micro-invasive groups (p = 0.53 and 0.798, respectively). CONCLUSION: Our data suggested for the massive basal ganglia hematomas, clot aspiration and thrombolysis can improve the short- and long-term prognosis compared with the pure conservative therapy. But, no evidence was found to demonstrate double target of this procedure to be more effective than single-target to improve the outcome. PMID- 27008454 TI - Contrasting effects of temperature and precipitation change on amphibian phenology, abundance and performance. AB - Climate change is determining a generalized phenological advancement, and amphibians are among the taxa showing the strongest phenological responsiveness to warming temperatures. Amphibians are strongly influenced by climate change, but we do not have a clear picture of how climate influences important parameters of amphibian populations, such as abundance, survival, breeding success and morphology. Furthermore, the relative impact of temperature and precipitation change remains underappreciated. We used Bayesian meta-analysis and meta regression to quantify the impact of temperature and precipitation change on amphibian phenology, abundance, individual features and performance. We obtained effect sizes from studies performed in five continents. Temperature increase was the major driver of phenological advancement, while the impact of precipitation on phenology was weak. Conversely, population dynamics was mostly determined by precipitation: negative trends were associated with drying regimes. The impact of precipitation on abundance was particularly strong in tropical areas, while the importance of temperature was feeble. Both temperature and precipitation influenced parameters representing breeding performance, morphology, developmental rate and survival, but the response was highly heterogeneous among species. For instance, warming temperature increased body size in some species, and decreased size in others. Similarly, rainy periods increased survival of some species and reduced the survival of others. Our study showed contrasting impacts of temperature and precipitation changes on amphibian populations. Both climatic parameters strongly influenced amphibian performance, but temperature was the major determinant of the phenological changes, while precipitation had the major role on population dynamics, with alarming declines associated with drying trends. PMID- 27008455 TI - Inflated Soft Actuators with Reversible Stable Deformations. AB - Most soft robotic systems are currently dependent on bulky compressors or pumps. A soft actuation method is presented combining hyperelastic membranes and dielectric elastomer actuators to switch between stable deformations of sealed chambers. This method is capable of large repeatable deformations, and has a number of stable states proportional to the number of actuatable membranes in the chamber. PMID- 27008456 TI - Meta-analysis shows that highly comminuted bicondylar tibial plateau fractures treated by single lateral locking plate give similar outcomes as dual plate fixation. AB - OBJECTIVES: This meta-analysis was conducted to compare the clinical outcomes of single lateral locking plate (SP) versus dual plate fixation (DP) for the repair of bicondylar tibial plateau fractures (AO/OTA type C or Schatzker type V and VI). METHODS: PubMed, Embase, Medline, CNKI, Wanfang database and Chinese VIP information were searched to identify the randomized and prospective comparative clinical studies which concern the treatment of bicondylar tibial plateau fractures (AO/OTA type C or Schatzker type V and VI) both with SP and DP fixation before October 1, 2015. STATA version 11.0 (Stata Corporation, College Station, TX, USA) was used for data-analysis after the critical assessment of the methodological quality of the trials. RESULTS: Finally, nine trials comprising 559 patients were included for this meta-analysis after the filtration. There were no significant differences between SP fixation and DP fixation with regards to outcomes for bone graft, post-operative malalignment and post-operative malreduciton in surgical details; infection, venous thrombosis, implant irritation and loss of reduction in complications; knee motion range in final outcomes. Lower surgical time, hospital stay, union time and incision necrosis were found in SP fixation compared with DP fixation. High rate of loss of alignment and more satisfaction with 12-month HSS score were associated with SP fixation than with DP fixation. CONCLUSIONS: Both SP fixation and DP fixation are acceptable strategies for managing this type of fracture. However, more high quality RCTs with large number of patients and long-term clinical evaluations are required to determine the optimal strategy for bicondylar tibial plateau fractures. PMID- 27008458 TI - The Activities-specific Balance Confidence scale: reliability and validity in Spanish patients with vestibular disorders. AB - PURPOSE: To examine the reliability and validity of the Spanish version of the Activities-specific Balance Confidence scale (ABC-S), and its ability to discriminate between patients with and without a history of falls among a Spanish population with vestibular disorders. METHOD: A total of 84 participants completed the ABC-S. Internal consistency, test-retest reliability and construct validity (exploratory factor analysis) were analysed. Concurrent validity was evaluated using the 12-item Short Form Health Survey (SF-12) and the Dizziness Handicap Inventory (DHI). To determine the accuracy of the ABC total score in discriminating patients with and without a history of falls, a receiver operating characteristic (ROC) curve analysis was performed. RESULTS: The ABC-S showed excellent internal consistency (Cronbach's alpha = 0.916) and substantial test retest reliability (ICC = 0.86, 95% CI: 0.74-0.93), with standard error and minimal detectable change values of 8.64 and 16.94, respectively. Factor analyses suggested a three-factor structure (explained variance was 62.24%). The ABC total score significantly correlated with the physical component summary score of the SF-12 and with the DHI-P, DHI-E, DHI-F and DHI total scores (p < 0.001). The ABC S was significantly able to discriminate between participants with and without a history of falls (p < 0.006). CONCLUSIONS: The ABC-S is a valid and reliable instrument, suitable to assess balance confidence in Spanish patients with vestibular disorders. Implications for Rehabilitation The Spanish version of the ABC scale is a valid and reliable measure of balance confidence in patients with vestibular disorders. In persons with vestibular disorders, the Spanish version of the ABC scale has shown the ability to discriminate between patients with and without a history of falls in the last year. PMID- 27008459 TI - Proton therapy monitoring by Compton imaging: influence of the large energy spectrum of the prompt-gamma radiation. AB - In proton therapy, the prompt-gamma (PG) radiation produced by the interactions between protons and matter is related to the range of the beam in the patient. Tomographic Compton imaging is currently studied to establish a PG image and verify the treatment. However the quality of the reconstructed images depends on a number of factors such as the volume attenuation, the spatial and energy resolutions of the detectors, incomplete absorptions of high energy photons and noise from other particles reaching the camera. The impact of all these factors was not assessed in details. In this paper we investigate the influence of the PG energy spectrum on the reconstructed images. To this aim, we describe the process from the Monte Carlo simulation of the proton irradiation, through the Compton imaging of the PG distribution, up to the image reconstruction with a statistical MLEM method. We identify specific PG energy windows that are more relevant to detect discrepancies with the treatment plan. We find that for the simulated Compton device, the incomplete absorption of the photons with energy above about 2 MeV prevents the observation of the PG distributions at specific energies. It also leads to blurred images and smooths the distal slope of the 1D PG profiles obtained as projections on the central beam axis. We show that a selection of the events produced by gamma photons having deposited almost all their energy in the camera allows to largely improve the images, a result that emphasizes the importance of the choice of the detector. However, this initial-energy-based selection is not accessible in practice. We then propose a method to estimate the range of the PG profile both for specific deposited-energy windows and for the full spectrum emission. The method relies on two parameters. We use a learning approach for their estimation and we show that it allows to detect few millimeter shifts of the PG profiles. PMID- 27008457 TI - The key role of CYC2 during meiosis in Tetrahymena thermophila. AB - Meiotic recombination is carried out through a specialized pathway for the formation and repair of DNA double-strand breaks (DSBs) made by the Spo11 protein. The present study shed light on the functional role of cyclin, CYC2, in Tetrahymena thermophila which has transcriptionally high expression level during meiosis process. Knocking out the CYC2 gene results in arrest of meiotic conjugation process at 2.5-3.5 h after conjugation initiation, before the meiosis division starts, and in company with the absence of DSBs. To investigate the underlying mechanism of this phenomenon, a complete transcriptome profile was performed between wild-type strain and CYC2 knock-out strain. Functional analysis of RNA-Seq results identifies related differentially expressed genes (DEGs) including SPO11 and these DEGs are enriched in DNA repair/mismatch repair (MMR) terms in homologous recombination (HR), which indicates that CYC2 could play a crucial role in meiosis by regulating SPO11 and participating in HR. PMID- 27008460 TI - Ab Initio Calculation of Rate Constants for Molecule-Surface Reactions with Chemical Accuracy. AB - The ab initio prediction of reaction rate constants for systems with hundreds of atoms with an accuracy that is comparable to experiment is a challenge for computational quantum chemistry. We present a divide-and-conquer strategy that departs from the potential energy surfaces obtained by standard density functional theory with inclusion of dispersion. The energies of the reactant and transition structures are refined by wavefunction-type calculations for the reaction site. Thermal effects and entropies are calculated from vibrational partition functions, and the anharmonic frequencies are calculated separately for each vibrational mode. This method is applied to a key reaction of an industrially relevant catalytic process, the methylation of small alkenes over zeolites. The calculated reaction rate constants (free energies), pre-exponential factors (entropies), and enthalpy barriers show that our computational strategy yields results that agree with experiment within chemical accuracy limits (less than one order of magnitude). PMID- 27008461 TI - 7 T renal MRI: challenges and promises. AB - The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to inhomogeneity of the radiofrequency field and due to specific absorption rate (SAR) constraints. A number of studies has been published in the field of renal 7 T imaging. While the focus initially was on anatomic imaging and renal MR angiography, later studies have explored renal functional imaging. Although anatomic imaging remains somewhat limited by inhomogeneous excitation and SAR constraints, functional imaging results are promising. The increased SNR at 7 T has been particularly advantageous for blood oxygen level-dependent and arterial spin labelling MRI, as well as sodium MR imaging, thanks to changes in field-strength-dependent magnetic properties. Here, we provide an overview of the currently available literature on renal 7 T MRI. In addition, we provide a brief overview of challenges and opportunities in renal 7 T MR imaging. PMID- 27008463 TI - Preface. 11th International Phytotechnologies Conference, Heraklion, Crete, Greece, September 30-October 3, 2014. PMID- 27008462 TI - New Insights into IL-10 Dependent and IL-10 Independent Mechanisms of Regulatory B Cell Immune Suppression. AB - Regulatory B (Breg) cells are important regulators of immune responses and in recent years our understanding of their phenotypical and functional characteristics has improved considerably. Initially all suppressive capabilities of Breg cells were attributed to the actions of the anti-inflammatory cytokine interleukin (IL)-10 secreted by Breg cells. Recent studies however, highlight additional and novel mechanisms that influence both the expansion of Breg cells and their capacity to suppress immunity. Here we provide an overview of the complexity of Breg cell populations and address the newly discovered IL-10 independent mechanisms of Breg cell expansion and immune-suppression. PMID- 27008464 TI - The Hidden Health and Economic Burden of Rotavirus Gastroenteritis in Malaysia: An Estimation Using Multiple Data Sources. AB - BACKGROUND: Rotavirus gastroenteritis (RVGE) results in substantial mortality and morbidity worldwide. However, an accurate estimation of the health and economic burden of RVGE in Malaysia covering public, private and home treatment is lacking. METHODS: Data from multiple sources were used to estimate diarrheal mortality and morbidity according to health service utilization. The proportion of this burden attributable to rotavirus was estimated from a community-based study and a meta-analysis we conducted of primary hospital-based studies. Rotavirus incidence was determined by multiplying acute gastroenteritis incidence with estimates of the proportion of gastroenteritis attributable to rotavirus. The economic burden of rotavirus disease was estimated from the health systems and societal perspective. RESULTS: Annually, rotavirus results in 27 deaths, 31,000 hospitalizations, 41,000 outpatient visits and 145,000 episodes of home treated gastroenteritis in Malaysia. We estimate an annual rotavirus incidence of 1 death per 100,000 children and 12 hospitalizations, 16 outpatient clinic visits and 57 home-treated episodes per 1000 children under-5 years. Annually, RVGE is estimated to cost US$ 34 million to the healthcare provider and US$ 50 million to society. Productivity loss contributes almost a third of costs to society. Publicly, privately and home-treated episodes consist of 52%, 27% and 21%, respectively, of the total societal costs. CONCLUSIONS: RVGE represents a considerable health and economic burden in Malaysia. Much of the burden lies in privately or home-treated episodes and is poorly captured in previous studies. This study provides vital information for future evaluation of cost effectiveness, which are necessary for policy-making regarding universal vaccination. PMID- 27008465 TI - Incorrect Figure Key. PMID- 27008466 TI - Milk Flow Rates from bottle nipples used after hospital discharge. AB - PURPOSE: To test the milk flow rates and variability in flow rates of bottle nipples used after hospital discharge. STUDY DESIGN AND METHODS: Twenty-six nipple types that represented 15 common brands as well as variety in price per nipple and store location sold (e.g., Babies R' Us, Walmart, Dollar Store) were chosen for testing. Ten of each nipple type (n = 260 total) were tested by measuring the amount of infant formula expressed in 1 minute using a breast pump. Mean milk flow rate (mL/min) and coefficient of variation (CV) were calculated. Flow rates of nipples within brand were compared statistically. RESULTS: Milk flow rates varied from 1.68 mL/min for the Avent Natural Newborn Flow to 85.34 mL/min for the Dr. Brown's Standard Y-cut. Variability between nipple types also varied widely, from .03 for the Dr. Brown's Standard Level 3 to .37 for MAM Nipple 1 Slow Flow. CLINICAL IMPLICATIONS: The extreme range of milk flow rates found may be significant for medically fragile infants being discharged home who are continuing to develop oral feeding skills. The name of the nipple does not provide clear information about the flow rate to guide parents in decision making. Variability in flow rates within nipples of the same type may complicate oral feeding for the medically fragile infant who may not be able to adapt easily to change in flow rates. Both flow rate and variability should be considered when guiding parents to a nipple choice. PMID- 27008467 TI - Pre-cooling moderately enhances visual discrimination during exercise in the heat. AB - Pre-cooling has been reported to attenuate the increase in core temperature, although, information regarding the effects of pre-cooling on cognitive function is limited. The present study investigated the effects of pre-cooling on visual discrimination during exercise in the heat. Eight male recreational runners completed 90 min of treadmill running at 65% [Formula: see text]2max in the heat [32.4 +/- 0.9 degrees C and 46.8 +/- 6.4% relative humidity (r.h.)] on two occasions in a randomised, counterbalanced crossover design. Participants underwent pre-cooling by means of water immersion (20.3 +/- 0.3 degrees C) for 60 min or remained seated for 60 min in a laboratory (20.2 +/- 1.7 degrees C and 60.2 +/- 2.5% r.h.). Rectal temperature (Trec) and mean skin temperature (Tskin) were monitored throughout the protocol. At 30-min intervals participants performed a visual discrimination task. Following pre-cooling, Trec (P = 0.040; [Formula: see text] = 0.48) was moderately lower at 0 and 30 min and Tskin (P = 0.003; [Formula: see text] = 0.75) lower to a large extent at 0 min of exercise. Visual discrimination was moderately more accurate at 60 and 90 min of exercise following pre-cooling (P = 0.067; [Formula: see text] = 0.40). Pre-cooling resulted in small improvements in visual discrimination sensitivity (F1,7 = 2.188; P = 0.183; [Formula: see text] = 0.24), criterion (F1,7 = 1.298; P = 0.292; [Formula: see text] = 0.16) and bias (F1,7 = 2.202; P = 0.181; [Formula: see text] = 0.24). Pre-cooling moderately improves visual discrimination accuracy during exercise in the heat. PMID- 27008468 TI - Upper tract urothelial carcinoma: epidemiology, high risk populations and detection. AB - Upper tract urothelial carcinoma (UTUC) is a rare but highly morbid genitourinary malignancy. In 2014 approximately 15,000 new cases were diagnosed in the United States. It accounts for approximately 5-10% of all urothelial cell carcinomas, and 10% of renal tumors. Recent research has increased understanding of the epidemiology of this disease, including several high-risk populations. Environmental exposure to tobacco as well as aristolochic acid, and other carcinogens significantly increase the development of UTUC. Additionally, the genetic condition of hereditary nonpolyposis colorectal carcinoma (HNPCC), also known as Lynch Syndrome (LS) is linked to development of UTUC. Advances in imaging, ureteroscopy, cytological techniques and pathological recognition have allowed for improved detection of primary tumors and recurrent disease. Non invasive imaging with computed tomography (CT) and magnetic resonance imaging (MRI) now represent the gold standard in imaging detection and surveillance, while technological advances in ureteroscopy allow for minimally invasive approaches to obtain pathologic diagnosis anywhere within the upper tracts. This review will highlight these recent improvements to allow better understanding of who is affected by this rare and morbid disease, as well as the latest developments in detection and surveillance. PMID- 27008469 TI - Correction: Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers. PMID- 27008470 TI - Correction to Direct Measure of Metal-Ligand Bonding Replacing the Tolman Electronic Parameter. PMID- 27008471 TI - Rethinking diagnoses in rehabilitation: An educational case series. AB - OBJECTIVE: To review the diagnosis of patients transferred to rehabilitation unit. DESIGN: Case series. SUBJECTS: Five patients with functional decline were transferred from an acute care setting in a tertiary hospital to the rehabilitation unit. METHODS: Full clinical evaluation and clinical reasoning were applied in addition to multidisciplinary care. Functional outcome and discharge destination were noted in each case. RESULTS: All patients had a new diagnosis that evolved during their stay in the rehabilitation unit in addition to their existing conditions. The new diagnosis helped to direct their future treatment programme. Four patients had good outcomes; they gained significant functional independence and were discharged home. One patient had an adverse outcome. CONCLUSION: In addition to multidisciplinary care, it is important to review the medical diagnosis in the rehabilitation unit. Diagnostic errors can have profound effect on the lives of patients with already existing impairments. Rehabilitation physicians should avoid making assumptions or diagnostic biases, and reapply clinical reasoning especially in the care of individuals with functional decline in rehabilitation. PMID- 27008472 TI - Stereological quantification of microvessels using semiautomated evaluation of X ray microtomography of hepatic vascular corrosion casts. AB - PURPOSE: Quantitative description of hepatic microvascular bed could contribute to understanding perfusion CT imaging. Micro-CT is a useful method for the visualization and quantification of capillary-passable vascular corrosion casts. Our aim was to develop and validate open-source software for the statistical description of the vascular networks in micro-CT scans. METHODS: Porcine hepatic microvessels were injected with Biodur E20 resin, and the resulting corrosion casts were scanned with 1.9-4.7 [Formula: see text] resolution. The microvascular network was quantified using newly developed QuantAn software both in randomly selected volume probes (n = 10) and in arbitrarily outlined hepatic lobules (n = 4). The volumes, surfaces, lengths, and numbers of microvessel segments were estimated and validated in the same data sets with manual stereological counting. Calculations of tortuosity, radius histograms, length histograms, exports of the skeletonized vascular network into open formats, and an assessment of the degree of their anisotropy were performed. RESULTS: Within hepatic lobules, the microvessels had a volume fraction of 0.13 [Formula: see text] 0.05, surface density of 21.0 [Formula: see text] 2.0 [Formula: see text], length density of 169.0 [Formula: see text] 40.2 [Formula: see text], and numerical density of 588.5 [Formula: see text] 283.1 [Formula: see text]. Sensitivity analysis of the automatic analysis to binary opening, closing, threshold offset, and aggregation radius of branching nodes was performed. CONCLUSION: The software QuantAn and its source code are openly available to researchers working in the field of stochastic geometry of microvessels in micro-CT scans or other three-dimensional imaging methods. The implemented methods comply with reproducible stereological techniques, and they were highly consistent with manual counting. Preliminary morphometrics of the classical hepatic lobules in pig were provided. PMID- 27008473 TI - Vision-based deformation recovery for intraoperative force estimation of tool tissue interaction for neurosurgery. AB - PURPOSE: In microsurgery, accurate recovery of the deformation of the surgical environment is important for mitigating the risk of inadvertent tissue damage and avoiding instrument maneuvers that may cause injury. The analysis of intraoperative microscopic data can allow the estimation of tissue deformation and provide to the surgeon useful feedback on the instrument forces exerted on the tissue. In practice, vision-based recovery of tissue deformation during tool tissue interaction can be challenging due to tissue elasticity and unpredictable motion. METHODS: The aim of this work is to propose an approach for deformation recovery based on quasi-dense 3D stereo reconstruction. The proposed framework incorporates a new stereo correspondence method for estimating the underlying 3D structure. Probabilistic tracking and surface mapping are used to estimate 3D point correspondences across time and recover localized tissue deformations in the surgical site. RESULTS: We demonstrate the application of this method to estimating forces exerted on tissue surfaces. A clinically relevant experimental setup was used to validate the proposed framework on phantom data. The quantitative and qualitative performance evaluation results show that the proposed 3D stereo reconstruction and deformation recovery methods achieve submillimeter accuracy. The force-displacement model also provides accurate estimates of the exerted forces. CONCLUSIONS: A novel approach for tissue deformation recovery has been proposed based on reliable quasi-dense stereo correspondences. The proposed framework does not rely on additional equipment, allowing seamless integration with the existing surgical workflow. The performance evaluation analysis shows the potential clinical value of the technique. PMID- 27008474 TI - Does systemic inflammation and immune activation contribute to fracture risk in HIV? AB - PURPOSE OF REVIEW: There is increasing evidence pointing toward an important role of heightened immune activation and inflammation in people living with HIV contributing to the development of non-AIDS comorbidities. This review aims to explore low bone mineral density (BMD) in HIV with a focus on the underlying mechanisms and relationships between the immune and skeletal systems. RECENT FINDINGS: Baseline immune activation and inflammation negatively impact BMD at antiretroviral therapy (ART) initiation. B- and T-cell alterations in HIV lead to an imbalance in the osteoblastic osteoprotegerin (OPG) and osteoclastic receptor activator of NF-kappaB ligand (RANKL) cytokines which favours osteoclastogenesis and bone resorption. These findings suggest an important role for immune-mediated mechanisms in the pathogenesis of low BMD in HIV. SUMMARY: Bone homeostasis is in part regulated by cells of the immune system through complex interactions with the RANK/RANKL/OPG axis. Disturbances in the normal functioning of T, B cells, and monocytes in HIV and the resulting proinflammatory state may contribute to dysregulation of this finely controlled balance leading to increased bone loss. Pre-ART levels of immune activation and inflammation have a consistently negative effect on BMD and further suggest the immunocentric basis of bone loss in HIV alongside supporting the benefits of earlier ART initiation. Further longitudinal studies will help determine the effect this will have on fracture risk in people living with HIV. PMID- 27008475 TI - Attentional Bias towards Positive Emotion Predicts Stress Resilience. AB - There is extensive evidence for an association between an attentional bias towards emotionally negative stimuli and vulnerability to stress-related psychopathology. Less is known about whether selective attention towards emotionally positive stimuli relates to mental health and stress resilience. The current study used a modified Dot Probe task to investigate if individual differences in attentional biases towards either happy or angry emotional stimuli, or an interaction between these biases, are related to self-reported trait stress resilience. In a nonclinical sample (N = 43), we indexed attentional biases as individual differences in reaction time for stimuli preceded by either happy or angry (compared to neutral) face stimuli. Participants with greater attentional bias towards happy faces (but not angry faces) reported higher trait resilience. However, an attentional bias towards angry stimuli moderated this effect: The attentional bias towards happy faces was only predictive for resilience in those individuals who also endorsed an attentional bias towards angry stimuli. An attentional bias towards positive emotional stimuli may thus be a protective factor contributing to stress resilience, specifically in those individuals who also endorse an attentional bias towards negative emotional stimuli. Our findings therefore suggest a novel target for prevention and treatment interventions addressing stress-related psychopathology. PMID- 27008476 TI - Hit Identification of a Novel Dual Binder for h-telo/c-myc G-Quadruplex by a Combination of Pharmacophore Structure-Based Virtual Screening and Docking Refinement. AB - It is well known that G-quadruplexes are targets of great interest for their roles in crucial biological processes, such as aging and cancer. Hence, a promising strategy for anticancer drug therapy is the stabilization of these structures by small molecules. We report a high-throughput in silico screening of commercial libraries from several different vendors by means of a combined structure-based pharmacophore model approach followed by docking simulations. The compounds selected by the virtual screening procedure were then tested for their ability to interact with human telomeric G-quadruplex folding by circular dichroism, fluorescence spectroscopy, and fluorescence intercalator displacement. Our approach resulted in the identification of a 13-[(dimethylamino)methyl]-12 hydroxy-8H-benzo[c]indolo[3,2,1-ij][1,5]naphthyridin-8-one derivative as a novel promising stabilizer of G-quadruplex structures within the human telomeric and the c-myc promoter sequences. PMID- 27008477 TI - Alleles of organic acid transporter genes are highly correlated with wheat resistance to acidic soil in field conditions. AB - KEY MESSAGE: TaALMT1 and TaMATE1B promoter alleles are highly correlated with wheat growth in acidic soil with a high concentration of toxic aluminium. The aluminium (Al(3+)) resistance of 338 wheat genotypes with different geographic origins was correlated with morphological traits and TaALMT1 and TaMATE1B alleles. Both of these genes encode malate and citrate transporters associated with Al(3+) resistance mechanisms in wheat. Based on comparisons with the sensitive and resistant controls, the relative root growth was evaluated in hydroponic experiments and the plant performance was visually accessed in the field. The correlation between Al(3+) tolerance in the hydroponic and field tests was moderate (r = 0.56, P < 0.001). Higher selection pressure was observed in the field because a smaller number of genotypes was classified as resistant. The combination between the six TaALMT1 alleles and the two TaMATE1B promoters allowed the identification of 11 haplotypes that showed a high (r = 0.71, P < 0.001) correlation with Al(3+) resistance in the field, with the TaALMT1 alleles accounting for most of the correlation. The Brazilian wheat genotypes presented the best performance in soil, including eight cultivars with promoters usually associated with Al(3+) resistance and another six genotypes classified as moderately resistant but containing alleles usually associated with Al(3+) sensitivity. Although an increase in favourable alleles was observed over the past few decades, the average Al(3+) resistance in the field was not significantly different from that of older cultivars. The ease identification of the TaALMT1 and TaMATE1B alleles and their higher association with Al(3+) resistance along with the best genotypes identified here may be used for wheat breeding programmes interested in increasing wheat Al(3+) resistance. PMID- 27008478 TI - Spatio-Temporal Distribution of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) and Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae) in a Cotton Production Area. AB - Helicoverpa armigera (Hubner) and Pectinophora gossypiella (Saunders) are major pests of cotton in Greece and elsewhere. Analysing male captures in pheromone traps over two seasons, in two cotton producing sites in central Greece, the spatial and temporal variation in population dynamics were examined. In 2007, captures of male H. armigera increased in late July and maintained at high levels for 1 month and declined at the end of August. For P. gossypiella, male captures remained at low levels during summer, increased late in August, peaked at mid of September and declined toward the end of the season. In 2008, trap captures of both species increased sharply by the end of June and remained at relatively high levels until August and September for P. gossypiella and H. armigera, respectively. Spatial analysis produced a spatial trend map over space, a temporal stability map over time and a spatial and temporal trend map for both species, which could lead in separating the field into management zones, and direct control to areas that exhibit high densities of the pest population and are stable over time. PMID- 27008479 TI - PhotoCORMs: CO release moves into the visible. AB - The potential of carbon monoxide to act as a therapeutic agent is now well established. Controlled delivery of CO is best achieved using 'CORMs': molecules which release known amounts of carbon monoxide in response to a stimulus. Metal carbonyl complexes will release CO if irradiated with ultraviolet light, but it is only in the past five years that development of true 'photoCORMs' has been explored. Recent exciting developments in this area now show that design of photoCORMs operating well into the visible region is achievable. In this Perspective, we examine the growth of photoCORMs from their origins in the photophysics of metal carbonyls to the latest visible-light agents. PMID- 27008480 TI - The future of thoracic oncology. PMID- 27008481 TI - Zika virus. PMID- 27008482 TI - Sports medicine and sports-related trauma. PMID- 27008483 TI - Videolaparoscopic appendectomy during pregnancy - gold standard. PMID- 27008485 TI - Cesarean delivery and small newborn for gestational age. PMID- 27008486 TI - Facial extensive ulcer. AB - Basosquamous carcinoma (BSC), as described in 1910, is a distinctive variety of skin cancer and its etiology and pathological characteristics have generated much controversy over the years. Currently, BSC is considered a basal cell carcinoma (BCC) subtype with aggressive behavior and greater tendency for recurrence and metastases. We present a clinical case recently reported in our unit. PMID- 27008487 TI - When should a patient be referred for bariatric surgery? PMID- 27008488 TI - Approach to the history of bioethics in the professional education of podiatry in Spain. PMID- 27008489 TI - "My (critically ill) patient has only a pneumonia" - the risk of oversimplification and the evidence of post-ICU syndrome. PMID- 27008490 TI - EuroSCORE II and STS as mortality predictors in patients undergoing TAVI. AB - INTRODUCTION: the EuroSCORE II and STS are the most used scores for surgical risk stratification and indication of transcatheter aortic valve implantation (TAVI). However, its role as a tool for mortality prediction in patients undergoing TAVI is still unclear. OBJECTIVE: to evaluate the performance of the EuroSCORE II and STS as predictors of in-hospital and 30-day mortality in patients undergoing TAVI. METHODS: we included 59 symptomatic patients with severe aortic stenosis that underwent TAVI between 2010 and 2014. The variables were analyzed using Student's t-test and Fisher's exact test and the discriminative power was evaluated using receiver operating characteristic curve (ROC) and area under the curve (AUC) with a 95% confidence interval. RESULTS: mean age was 81+/-7.3 years, 42.3% men. The mean EuroSCORE II was 7.6+/-7.3 % and STS was 20.7+/-10.3%. Transfemoral procedure was performed in 88.13%, transapical in 3.38% and transaortic in 8.47%. In-hospital mortality was 10.1% and 30-day mortality was 13.5%. Patients who died had EuroSCORE II and STS higher than the survivors (33.7+/-16.7vs. 18.6+/-7.3% p=0,0001 for STS and 13.9+/-16.1 vs. 4.8+/-3.8% p=0.0007 for EuroSCORE II). The STS showed an AUC of 0.81 and the EuroSCORE II of 0.77 and there were no differences in the discrimination ability using ROC curves (p=0.72). CONCLUSION: in this cohort, the STS and EuroSCORE II were predictors of in-hospital and 30-days mortality in patients with severe aortic stenosis undergoing TAVI. PMID- 27008491 TI - Physical activity, fatigue and quality of life in breast cancer patients. AB - OBJECTIVE: to evaluate the relationship between levels of physical activity, fatigue and quality of life (QOL) in women diagnosed with breast cancer. METHODS: 215 women between the ages of 40 and 65 years were recruited at a cancer clinic. Physical activity levels were assessed by using the International Physical Activity Questionnaire (IPAQ), fatigue levels by using the revised Piper scale, and QOL by means of EORTC QLQ-C30 and WHOQOL-Bref. Statistical analysis was performed using Minitab statistical software, version 16. RESULTS: the mean age of subjects was 52.66 years (SD=8.6); patients were mostly white (58.14%) and overweight (55.81%). Most women were fatigued (72.09%) while physically active women showed lower symptoms of fatigue (p<0.001). Mean scores for QOL were significantly lower among fatigued women (p<0.001). More active women scored higher on all scales of QOL (EORTC), especially for functional capacity (p<0.001), compared with the sedentary patients. A significant association was found between level of physical activity and overall QOL (WHOQOL-Bref) for all domains (p<0.001). Climacteric symptoms ranged from mild to strong and did not show any statistically significant results; however, the most active women had the fewest symptoms. CONCLUSION: physical activity appears to positively influence fatigue and QOL in women diagnosed with breast cancer. PMID- 27008492 TI - The potential influence of atherogenic dyslipidemia on the severity of chronic Chagas heart disease. AB - INTRODUCTION: chronic Chagas heart disease (CCHD) is the most common manifestation of American Trypanosomiasis, causing about 50,000 deaths annually. Several factors bear correlation with the severity of CCHD. However, to our knowledge, the assessment on the contribution of major cardiovascular risk factors (CRF), such as hypertension and atherogenic dyslipidemia (AD) to CCHD severity is scarce, despite their well-established role in coronary artery disease, heart failure and stroke. OBJECTIVE: to explore the potential relationship of blood pressure and AD with the clinical profile of patients with CCHD. METHODS: we performed a cross-sectional study in T. cruziseropositive patients categorized according to a standard CCHD classification. All individuals were subjected to complete clinical examination. Autoantibodies induced by T. cruzi were assessed by ELISA. RESULTS: we observed that Atherogenic index (AI) levels rose significantly in relation to the severity of the CCHD stage, with CCHD III cases showing the highest values of AI. Furthermore, those patients with globally dilated cardiomyopathy with reduced ejection fraction showed higher levels of AI. In regard to autoantibodies, anti-B13 also showed relation with the severity of the disease. CONCLUSION: we observed that AI correlated with CCHD stages and contributed, in association with anti-B13 antibodies and age, to the prediction of systolic heart failure. PMID- 27008493 TI - Smoking control at the School of Public Health, Universidade de Sao Paulo. AB - INTRODUCTION: schools of Public Health, by their nature, have increased responsibility in the development of health promotion programs, focusing on tobacco control. The participation of groups of health professionals in educational actions helps to convey information about smoking to the population. OBJECTIVE: to evaluate the prevalence of smoking and the effectiveness of control programs among the teaching and non-teaching staff of the School of Public Health of the Universidade de Sao Paulo (FSP-USP). They were monitored by surveys conducted from 1980 to 2013. METHODS: application of a questionnaire, containing the variables: identity, gender, smoking habit (are you a smoker, former smoker or non-smoker), which was answered in a private interview. Data analysis was done using absolute and relative frequencies. RESULTS: the prevalence of smokers had a reduction from 50.3%, in 1980, to 13.4%, in 2013; among males, prevalence fell from 56.9% to 12.8%, and among females from 45.9% to 13.7%. As for the teaching staff, there was a fall from 10.2% (2006) to 5.9% (2013); the decrease among non teaching employees was from 21.6% to 16.3%. CONCLUSION: knowledge by health professionals of the harms caused by tobacco smoking contributed to their participation in anti-smoking programs, and led to a decline in the number of smokers at FSP-USP. The creation of 100% tobacco-free environments and programs to treat smokers who want to cease their addiction should be encouraged. PMID- 27008494 TI - Predictive value of clinical history compared with urodynamic study in 1,179 women. AB - OBJECTIVE: to determine the positive predictive value of clinical history in comparison with urodynamic study for the diagnosis of urinary incontinence. METHODS: retrospective analysis comparing clinical history and urodynamic evaluation of 1,179 women with urinary incontinence. The urodynamic study was considered the gold standard, whereas the clinical history was the new test to be assessed. This was established after analyzing each method as the gold standard through the difference between their positive predictive values. RESULTS: the positive predictive values of clinical history compared with urodynamic study for diagnosis of stress urinary incontinence, overactive bladder and mixed urinary incontinence were, respectively, 37% (95% CI 31-44), 40% (95% CI 33-47) and 16% (95% CI 14-19). CONCLUSION: we concluded that the positive predictive value of clinical history was low compared with urodynamic study for urinary incontinence diagnosis. The positive predictive value was low even among women with pure stress urinary incontinence. PMID- 27008496 TI - Seroprevalence of HCV markers among HIV infected patients from Curitiba and metropolitan region. AB - OBJECTIVE: to determine the prevalence and epidemiological factors associated with hepatitis (HCV) coinfection in human immunodeficiency virus (HIV) patients from Curitiba and the metropolitan region. METHODS: a study with 303 HIV+ patients, mean age 41.2 years (18-73); 50.5% men, followed at the Hospital de Clinicas, Universidade Federal do Parana, between April 2008 and March 2009. Clinical and epidemiological data were obtained through questionnaires and retrospective analysis of medical records. Anti-HCV antibodies were detected by chemiluminescence immunoassay. RESULTS: a total of 12.9% of HIV+ patients were positive for anti-HCV antibodies, 64.1% were men and 35.9% women, with mean age of 44.5 years (24-66). The frequency of HCV among men was 16.7% and among women 9.1% (p=0.06). HCV prevalence was associated to HIV infection when compared to the general population (p<10-6, OR=100.4; 95CI=13.7-734.9). The parenteral route of transmission was the most frequent among coinfected patients (46.1%), and the sexual transmission among HIV+/HCV- (71.8%) (p=0.02, OR=0.2; 95CI=0.1-0.7). The frequency of intravenous drug users was higher among the coinfected patients (61.5%) compared to the non coinfected (12.6%) (p<10-6, OR=11.1; 95CI=4.5-27.7). CONCLUSION: the prevalence of coinfection with HCV in HIV+ patients is 12.9%, 88 times higher than in the general population in Curitiba. The most frequent route of transmission in the coinfected patients is parenteral, but the sexual route is also representative (34.6%). PMID- 27008495 TI - Outcome of children and adolescents with lymphoblastic lymphoma. AB - INTRODUCTION: lymphoblastic lymphoma (LBL) is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. METHODS: this is a retrospective cohort study of 27 patients aged 16 years or less with LBL admitted between January 1981 and December 2013. Patients received intensive chemotherapy regimen derived from acute lymphoblastic leukemia (ALL) therapy. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. RESULTS: the median age at diagnosis was 11.6 years (interquartile range, 4.6-13.8). LBL had T cell origin in 16 patients (59%). The most common primary manifestation in T-cell LBL was mediastinum involvement in 9 patients (56%). Intra-abdominal tumor was the major site of involvement in patients with pB-LBL. Most patients had advanced disease (18 patients - 67%) at diagnosis. Twenty-four patients (89%) achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95), 22 patients (81%) were alive in first complete remission. Five children (18.5%) died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4). CONCLUSION: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy. PMID- 27008497 TI - Estrogen signaling in the proliferative endometrium: implications in endometriosis. AB - Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis. PMID- 27008498 TI - Advances in the endovascular treatment of direct carotid-cavernous fistulas. AB - Carotid cavernous fistulas (CCFs) are abnormal connections between the carotid artery and the cavernous sinus. They are considered direct when there is a direct connection between the internal carotid artery and the cavernous sinus. These cases are generally traumatic. Direct CCFs are high-flow lesions, possibly related to intracranial bleeding, visual loss, corneal exposure or even fatal epistaxis. Treatment of such lesions is, thus, always recommended. The ideal treatment for direct CCF is to exclude the fistula from circulation, preserving the carotid flow. This can be attained using diverse endovascular techniques. The objective of the present article is to review the current techniques for treatment of direct CCFs, with special attention to the currently available endovascular treatment options. PMID- 27008499 TI - Cerebral aneurysms associated with human immunodeficiency virus in adults: literature review and new perspectives. AB - INTRODUCTION: the treatment of human immunodeficiency virus (HIV) infection has been decreasing patient morbidity and mortality by opportunistic infections and, thus, survival has increased. This new reality has been changing the spectrum of diseases affecting such patients. OBJECTIVE: to discuss the association between HIV and the emergence of aneurysmal brain injuries. METHOD: it was performed a literature review using medical database. The following descriptors were searched: "Intracranial Aneurysms and HIV", "Intracranial Aneurysms and Acquired Immunodeficiency Syndrome," "aneurysm and brain and HIV". RESULTS: after performed a literature review, it was observed that the relationship between HIV infection and the formation of aneurysms appears to be real, however, it still lacks data to confirm the pathophysiology of this condition and its best treatment. CONCLUSION: there are new signs and symptoms that should be studied and researched relating HIV with other changes not previously known. PMID- 27008500 TI - Folic acid and diseases - supplement it or not? AB - INTRODUCTION: folic acid is a water soluble vitamin, which is synthetically produced and found in fortified foods and supplements. Folate is found naturally in plants, such as the dark green leafy vegetables. Folate is not synthesized de novo by humans, therefore the daily requirements are met from the dietary intake of folic acid supplements or food rich in this vitamin. Folate deficiency could lead to numerous common health problems. Hyperhomocysteinemia and the possibility of malignancy developments are the long term consequences of this deficit albeit contradictory findings on these claims. METHODS: the articles included in this review focused on recent updated evidence-based reports and meta-analyses on the associations of the serum folate/folic acid and the various diseases found globally. RESULTS: the benefit of folic acid supplementation in the pre conception period for the prevention of neural tube defects (NTDs) was well established and it was suggested that counseling sessions should be given to women with previous pregnancies affected by NTDs. However, supplementation of folic acid and its medicinal effects in the treatment of other diseases were contradictory and unclear. CONCLUSION: more detailed investigations into the health benefits of folic acid are needed before it could be recommended for supplementation, treatment or prevention of some of the diseases discussed in this review. PMID- 27008501 TI - An SBSM Board of Directors Statement on Sleep Coaching. PMID- 27008502 TI - Real-time transformation of outdoor aerosol components upon transport indoors measured with aerosol mass spectrometry. AB - Outdoor aerosols are transported indoors, where their component concentrations depend on aerosol size, physiochemical properties, indoor sources and losses, and cross-environment gradients of temperature and relative humidity. We explored these dependencies by measuring real-time outdoor and indoor non-refractory, submicron (PM1 ) aerosol component mass concentrations in a mixed-use laboratory space with an Aerodyne mini-aerosol mass spectrometer (AMS) and black carbon (BC) with an aethalometer. The median indoor/outdoor (I/O) ratios were 0.60 for sulfate, 0.25 for nitrate, 0.52 for ammonium, 0.73 for organics, and 0.61 for BC. Positive matrix factorization (PMF) on organic aerosol data identified hydrocarbon-like (HOA), cooking (COA), and oxygenated (OOA) factors. By assuming sulfate was nonvolatile, lost only by mechanical processes, and without indoor sources, the transformations of other components i due to partitioning changes or indoor sources were parameterized by normalizing their I/O ratios by sulfate's I/O ratio, that is, (I/O)i/SO4 . Component-specific behavior was quantified by regressions of (I/O)i/SO4 to outdoor-to-indoor temperature differences. Nitrate and HOA strongly and OOA weakly showed losses with increasing temperatures indoors vs. outdoors, and HOA likely had an indoor source. To our knowledge, this is the first reported deployment of an AMS to analyze real-time indoor aerosol composition and outdoor-to-indoor transformation. PMID- 27008503 TI - Reduction in Cell Viability and in Homeobox Protein Levels Following in Vitro Exposure to delta-tocopherol in Acute Myeloid Leukemia. AB - delta-Tocopherol (delta-T), the least prevalent tocopherol in our diet, was described to have a more potent anticancer activity in solid tumors compared to the other tocopherols. delta-T induces tumor cell death through peroxisome proliferator-activated receptor gamma (PPAR-gamma) induction, cyclin-D1 inhibition, and modulation of redox balance. Nevertheless, the role of delta-T in preventing or treating hematologic malignancies has not been studied. In this study, we screened the efficacy of delta-T against six cell lines representing a wide spectrum of hematologic malignancies: Jurkat (acute T-cell leukemia), K-562 (chronic myeloid leukemia), KG-1 [acute myeloid leukemia (AML)], THP-1 (acute monocytic leukemia), TOM-1 (acute lymphoblastic leukemia), and UMCL01-101 (AIDS associated diffuse large B-cell lymphoma). Interestingly, the AML cell line KG-1 was the only one to be significantly affected at concentrations of delta-T as low as 20 uM. The antileukemic activity of delta-T in AML was verified in a set of primary cells collected from patients newly diagnosed with AML. Apoptotic induction and cell cycle arrest explained the efficacy of delta-T against KG-1 cells. The mechanism of cell growth inhibition of delta-T was through downregulation of cyclin-D1 and a set of homeobox proteins (HOXA9, PBX1, and Cdx2) that have a well-documented role in the pathobiology of AML. PMID- 27008504 TI - Preparing a neuropediatric upper limb exergame rehabilitation system for home use: a feasibility study. AB - BACKGROUND: Home-based, computer-enhanced therapy of hand and arm function can complement conventional interventions and increase the amount and intensity of training, without interfering too much with family routines. The objective of the present study was to investigate the feasibility and usability of the new portable version of the YouGrabber(r) system (YouRehab AG, Zurich, Switzerland) in the home setting. METHODS: Fifteen families of children (7 girls, mean age: 11.3y) with neuromotor disorders and affected upper limbs participated. They received instructions and took the system home to train for 2 weeks. After returning it, they answered questions about usability, motivation, and their general opinion of the system (Visual Analogue Scale; 0 indicating worst score, 100 indicating best score; <=30 not satisfied, 31-69 average, >=70 satisfied). Furthermore, total pure playtime and number of training sessions were quantified. To prove the usability of the system, number and sort of support requests were logged. RESULTS: The usability of the system was considered average to satisfying (mean 60.1-93.1). The lowest score was given for the occurrence of technical errors. Parents had to motivate their children to start (mean 66.5) and continue (mean 68.5) with the training. But in general, parents estimated the therapeutic benefit as high (mean 73.1) and the whole system as very good (mean 87.4). Children played on average 7 times during the 2 weeks; total pure playtime was 185 +/- 45 min. Especially at the beginning of the trial, systems were very error prone. Fortunately, we, or the company, solved most problems before the patients took the systems home. Nevertheless, 10 of 15 families contacted us at least once because of technical problems. CONCLUSIONS: Despite that the YouGrabber(r) is a promising and highly accepted training tool for home-use, currently, it is still error-prone, and the requested support exceeds the support that can be provided by clinical therapists. A technically more robust system, combined with additional attractive games, likely results in higher patient motivation and better compliance. This would reduce the need for parents to motivate their children extrinsically and allow for clinical trials to investigate the effectiveness of the system. TRIAL REGISTRATION: ClinicalTrials.gov NCT02368223. PMID- 27008505 TI - RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2. AB - Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL), adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2) was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression. PMID- 27008506 TI - Highly Viscous Binary Solvents: DMSO-d6/Glycerol and DMSO-d6/Glycerol-d8 for Polar and Apolar Mixture Analysis by NMR. AB - The use of two new highly viscous binary solvents, DMSO-d6/glycerol (GL) and DMSO d6/glycerol-d8 (GL-d8), is reported for the first time in order to give access to the individual NMR spectra of mixture components. Their high dissolution power offers a wide range of potential applications to mixture analysis, regardless of polarity. Under particular conditions of viscosity, the tumbling rate of small and medium-sized molecules slows down in solution, so that the longitudinal cross relaxation regime favors the observation of spin diffusion. As a consequence, all the resonances of the (1)H nuclei within the same molecule tend to correlate together in a 2D nuclear Overhauser effect spectroscopy (NOESY) spectrum, thus opening the way to mixture analysis. This work reports the analysis of a polar mixture composed of Leu-Val, Leu-Tyr, Gly-Tyr, and Ala-Tyr dissolved in DMSO d6/GL (8:2, v/v) and of an apolar mixture made of beta-ionone, (+/-)-citronellal, (+)-limonene, and flavone dissolved in DMSO-d6/GL-d8 (5:5, v/v) by means of spin diffusion in homonuclear selective 1D NOESY, selective 2D NOESY, NOESY correlation spectroscopy (COSY), NOESY-total correlation spectroscopy (TOCSY) experiments, and 2D heteronuclear single-quantum correlation spectroscopy (HSQC) NOESY. DMSO-d6/GL must be preferred to DMSO-d6/GL-d8 for the study of biological active compounds in which labile protons must not be exchanged by deuterium nuclei. DMSO-d6/GL-d8 is more appropriate for organic compounds in which labile protons are not essential to the structure elucidation. DMSO-d6/GL and DMSO-d6/GL d8 binary mixture solvents seem to be so far the most efficient viscous solvents described in the literature for the resolution of both polar and apolar complex mixtures components by NMR spin diffusion. PMID- 27008507 TI - Portuguese American gay men in southeastern Massachusetts: cultural scripts and risk for HIV. AB - In this study, we examined the lived experiences of an understudied subgroup, Portuguese American gay men, within the context of sexual script theory. We employed a phenomenological study design with eight men to provide a more in depth analysis of their sociocultural sexual behaviours. Recruitment was conducted through word of mouth and a snowball approach beginning with two well known HIV education and prevention outreach centres in southeastern Massachusetts. In this study, the sexual scripts of the participants were conceptualised within the three domains of cultural, interpersonal and intrapsychic scripts. Our findings suggest the three scripts are constantly interacting and informing one another. This ongoing negotiation influences the way our participants position their sexuality within the broader context of their everyday life within the US Portuguese community. Participants script their sexuality while they navigate multiple but separate entities within their culture, their religion and their families. Learning from these experiences could have important implications for the development of HIV prevention programmes for specific subgroups of men who have sex with men. PMID- 27008508 TI - Puerarin Exerts a Delayed Inhibitory Effect on the Proliferation of Cardiomyocytes Derived from Murine ES Cells via Slowing Progression through G2/M Phase. AB - OBJECTIVE: Puerarin, which shows beneficial and protective effects on cardiovascular diseases, is the main isoflavone extracted from Pueraria lobata (kudzu) root. The aim of this study was to investigate the effects of puerarin on in vitro myocardial proliferation and its underlying mechanism. METHODS: Myocardial differentiation of transgenic embryonic stem (ES) cells was performed by embryoid body-based differentiation method. The proliferation assay of cardiomyocytes (CMs) derived from ES cells (ES-CMs) was performed by EdU (5 Ethynyl-2'-deoxyuridine) staining. Flow cytometry was employed to determine the cell cycle distribution and apoptosis of purified ES-CMs. Quantitative real-time PCR was utilized to study the transcription of genes related to cell cycle progression. Signaling pathways relating to proliferation were studied by western blot analysis and application of specific inhibitors. RESULTS: Puerarin exerted a delayed inhibitory effect on the proliferation of ES-CMs at the early-stage differentiation. Meanwhile, puerarin slowed progression through G2/M phase without inducing apoptosis of ES-CMs. Further assays showed that puerarin up regulated the transcription of Cyclin A2, Cyclin B1 and Cdk1 in ES-CMs. The ERK1/2 specific inhibitor PD0325901 and the PI3K specific inhibitor Wortmannin successfully reversed puerarin-induced up-regulation of Cdk1 but not Cyclin A2 and B1. CONCLUSION: These findings suggest that puerarin inhibits CM proliferation via slowing progression through G2/M phase during early-stage differentiation. PMID- 27008510 TI - Algal taxonomy forum: Algal Taxonomist, Let Serendipity Reign! AB - The publication of a mini-review by Olivier De Clerck et al. in this issue of the Journal of Phycology presented an opportunity to open a dialogue on challenges faced by contemporary algal taxonomists. The Editorial Office solicited the following two additional contributions in response to De Clerck et al.'s paper; the responses were edited solely for clarity, space and format. PMID- 27008509 TI - Algal taxonomy: a road to nowhere? AB - The widespread view of taxonomy as an essentially retrogressive and outmoded science unable to cope with the current biodiversity crisis stimulated us to analyze the current status of cataloguing global algal diversity. Contrary to this largely pessimistic belief, species description rates of algae through time and trends in the number of active taxonomists, as revealed by the web resource AlgaeBase, show a much more positive picture. More species than ever before are being described by a large community of algal taxonomists. The lack of any decline in the rate at which new species and genera are described, however, is indicative of the large proportion of undiscovered diversity and bears heavily on any prediction of global algal species diversity and the time needed to catalogue it. The saturation of accumulation curves of higher taxa (family, order, and classes) on the other hand suggest that at these taxonomic levels most diversity has been discovered. This reasonably positive picture does not imply that algal taxonomy does not face serious challenges in the near future. The observed levels of cryptic diversity in algae, combined with the shift in methods used to characterize them, have resulted in a rampant uncertainty about the status of many older species. As a consequence, there is a tendency in phycology to move gradually away from traditional names to a more informal system whereby clade-, specimen- or strain-based identifiers are used to communicate biological information. Whether these informal names for species-level clades represent a temporary situation stimulated by the lag between species discovery and formal description, or an incipient alternative or parallel taxonomy, will be largely determined by how well we manage to integrate historical collections into modern taxonomic research. Additionally, there is a pressing need for a consensus about the organizational framework to manage the information about algal species names. An eventual strategy should preferably come out of an international working group that includes the various databases as well as the various phycological societies. In this strategy, phycologists should link up to major international initiatives that are currently being developed, such as the compulsory registration of taxonomic and nomenclatural acts and the introduction of Life Science Identifiers. PMID- 27008511 TI - Algal taxonomy forum: Algal Taxonomy: Ready to Play. PMID- 27008512 TI - Protists in Arctic drift and land-fast sea ice. AB - Global climate change is having profound impacts on polar ice with changes in the duration and extent of both land-fast ice and drift ice, which is part of the polar ice pack. Sea ice is a distinct habitat and the morphologically identifiable sympagic community living within sea ice can be readily distinguished from pelagic species. Sympagic metazoa and diatoms have been studied extensively since they can be identified using microscopy techniques. However, non-diatom eukaryotic cells living in ice have received much less attention despite taxa such as the dinoflagellate Polarella and the cercozoan Cryothecomonas being isolated from sea ice. Other small flagellates have also been reported, suggesting complex microbial food webs. Since smaller flagellates are fragile, often poorly preserved, and are difficult for non-experts to identify, we applied high throughput tag sequencing of the V4 region of the 18S rRNA gene to investigate the eukaryotic microbiome within the ice. The sea ice communities were diverse (190 taxa) and included many heterotrophic and mixotrophic species. Dinoflagellates (43 taxa), diatoms (29 taxa) and cercozoans (12 taxa) accounted for ~80% of the sequences. The sympagic communities living within drift ice and land-fast ice harbored taxonomically distinct communities and we highlight specific taxa of dinoflagellates and diatoms that may be indicators of land-fast and drift ice. PMID- 27008513 TI - Phosphate-limited growth of the marine diatom Thalassiosira weissflogii (Bacillariophyceae): evidence of non-monod growth kinetics(1). AB - The marine diatom Thalassiosira weissflogii (Grunow) G. A. Fryxell & Hasle was grown in a chemostat over a series of phosphate-limited growth rates. Ambient substrate concentrations were determined from bioassays involving picomolar spikes of (33) P-labeled phosphate, and maximum uptake rates were determined from analogous bioassays that included the addition of micromolar concentrations of unlabeled phosphate and tracer concentrations of (33) P. The relationship between cell phosphorus quotas and growth rates was well described by the Droop equation. Maximum uptake rates of phosphate spikes were several orders of magnitude higher than steady state uptake rates. Despite the large size of the T. weissflogii cells, diffusion of phosphate through the boundary layer around the cells had little effect on growth kinetics, in part because the cellular N:P ratios exceeded the Redfield ratio at all growth rates. Fitting the Monod equation to the experimental data produced an estimate of the nutrient-saturated growth rate that was ~50% greater than the maximum growth rate observed in batch culture. A modified hyperbolic equation with a curvature that is a maximum in magnitude at positive growth rates gave a better fit to the data and an estimate of the maximum growth rate that was consistent with observations. The failure of the Monod equation to describe the data may reflect a transition from substrate to co substrate limitation and/or the presence of an inducible uptake system. PMID- 27008514 TI - Patterns and controls of the dynamics of net primary production by understory macroalgal assemblages in giant kelp forests. AB - Macroalgae are important primary producers in many subtidal habitats, yet little information exists on the temporal and spatial dynamics of net primary production (NPP) by entire subtidal assemblages. This knowledge gap reflects the logistical challenges in measuring NPP of diverse macroalgal assemblages in shallow marine habitats. Here, we couple a simple primary production model with nondestructive estimates of taxon-specific biomass on subtidal reefs off Santa Barbara, California to produce a 4-year time series of net primary production by intact assemblages of understory macroalgae in giant kelp forests off Santa Barbara, California, USA. Daily bottom irradiance varied significantly throughout the year, and algal assemblages were on average exposed to saturating irradiance for only 1.3-4.5 h per day, depending on the time of year. Despite these variable light-limiting conditions, biomass rather than irradiance explained the vast majority of variation observed in daily NPP at all times of the year. Measurements of peak biomass in spring and summer proved to be good predictors of NPP for the entire year, explaining as much as 76% of the observed variation. In contrast, bottom irradiance was a poor predictor of NPP, explaining <10% of the variation in NPP when analyzed seasonally and ~2% when evaluated annually. Our finding that annual NPP by macroalgal assemblages can be predicted from a single, nondestructive measurement of biomass should prove useful for developing time series data that are necessary to evaluate natural and anthropogenic changes in NPP by one of the world's most productive ecosystems. PMID- 27008515 TI - Structure and diversity of intertidal benthic diatom assemblages in contrasting shores: a case study from the Tagus estuary(1). AB - The structure of intertidal benthic diatoms assemblages in the Tagus estuary was investigated during a 2-year survey, carried out in six stations with different sediment texture. Nonparametric multivariate analyses were used to characterize spatial and temporal patterns of the assemblages and to link them to the measured environmental variables. In addition, diversity and other features related to community physiognomy, such as size-class or life-form distributions, were used to describe the diatom assemblages. A total of 183 diatom taxa were identified during cell counts and their biovolume was determined. Differences between stations (analysis of similarity (ANOSIM), R = 0.932) were more evident than temporal patterns (R = 0.308) and mud content alone was the environmental variable most correlated to the biotic data (BEST, rho = 0.863). Mudflat stations were typically colonized by low diversity diatom assemblages (H' ~ 1.9), mainly composed of medium-sized motile epipelic species (250-1,000 MUm(3) ), that showed species-specific seasonal blooms (e.g., Navicula gregaria Donkin). Sandy stations had more complex and diverse diatom assemblages (H' ~ 3.2). They were mostly composed by a large set of minute epipsammic species (<250 MUm(3) ) that, generally, did not show temporal patterns. The structure of intertidal diatom assemblages was largely defined by the interplay between epipelon and epipsammon, and its diversity was explained within the framework of the Intermediate Disturbance Hypothesis. However, the spatial distribution of epipelic and epipsammic life-forms showed that the definition of both functional groups should not be over-simplified. PMID- 27008516 TI - Polyphasic characterization of benthic cyanobacterial diversity from biofilms of the Guadarrama river (Spain): morphological, molecular, and ecological approaches(1). AB - The occurrence and environmental factors responsible for the distribution of benthic cyanobacteria in running waters remain largely unexplored in comparison with those of other aquatic ecosystems. In this study, combined data of ecological characteristics, molecular analysis (based on 16S rRNA gene), and direct microscopic inspection of environmental samples were analyzed in parallel with the morphological characterization of the isolated strains to investigate benthic cyanobacterial diversity in the Guadarrama river (Spain). A total of 17 species were identified that belonged to the genera Aphanocapsa, Pleurocapsa, Chroococcus, Chamaesiphon, Cyanobium, Pseudan-abaena, Leptolyngbya, Phormidium, Nostoc, and Tolypothrix. Phenotypic features were associated with the results of 16S rRNA gene sequencing, complementing existing morphological and genetic databases. A decrease in the cyanobacterial diversity was observed along a pollution gradient in the river. Water quality differed among the sampling sites, and variation in nutrient content was the principal difference among locations. These characteristics were closely associated with an upstream-downstream eutrophic gradient. Canonical correspondence analysis distinguished three groups of species with respect to the eutrophication gradient. The first group (Tolypothrix cf. tenuis, Nostoc punctiforme, Nostoc piscinale, Chamaesiphon investiens, Chroococcus minor, Leptolyngbya nostocorum, and Leptolyngbya tenuis) was characteristic of waters with low levels of nutrients. The second group (Cyanobium sp., Chamaesiphon polymorphus, Leptolyngbya boryana, Phormidium autumnale, Phormidium sp., and Aphanocapsa cf. rivularis) was characteristic of polluted waters, its members appearing mainly in great abundance under eutrophic hypertrophic conditions. The third group of species (Pseudanabaena catenata, Aphanocapsa muscicola, and Nostoc carneum) was present at upstream and downstream sites. PMID- 27008517 TI - Life Cycle of the pseudocolonial dinoflagellate Polykrikos kofoidii (Gymnodiniales, Dinoflagellata). AB - The athecate, pseudocolonial polykrikoid dinoflag-ellates show a greater morphological complexity than many other dinoflagellate cells and contain not only elaborate extrusomes but sulci, cinguli, flagellar pairs, and nuclei in multiple copies. Among polykrikoids, Polykrikos kofoidii is a common species that plays an important role as a grazer of toxic planktonic algae but whose life cycle is poorly known. In this study, the main life cycle stages of P. kofoidii were examined and documented for the first time. The formation of gametes, 2 zooid-1-nucleus stages very different from vegetative cells, was observed and the process of gamete fusion, isogamy, was recorded. Karyogamy followed shortly after completed plasmogamy. A complex reorganization of furrows (cinguli and sulci) and flagella followed zygote formation, resulting in a 4-zooid zygote with one nucleus. The fate of zygotes under different nutritional conditions was also investigated; well-fed zygotes were able to reenter the vegetative cycle via meiotic divisions as indicated by nuclear cyclosis. However, nuclear cyclosis was preceded by a presumably mitotic division of the primary zygote nucleus which by definition would imply that P. kofoidii has a diplohaplontic life cycle. Nuclear cyclosis in germlings hatched from spiny resting cysts indicate that these cysts are of zygote origin (hypnozygotes). Hypnozygote formation, cyst hatching, the morphology of the germling (a 1-zooid cell), and its development into a normal pseudocolony are documented here for the first time. There is evidence that P. kofoidii has a system of complex heterothallism. PMID- 27008518 TI - Effects of UVB Radiation on competition between the bloom-forming cyanobacterium Microcystis aeruginosa and the Chlorophyceae Chlamydomonas microsphaera(1). AB - The growth, photosynthetic characteristics, and competitive ability of three algal strains were investigated under different doses of ultraviolet-B (UVB) radiation (0, 0.285, and 0.372 W . m(-2) ). The organisms were the toxic bloom forming cyanobacterium Microcystis aeruginosa FACHB 912, nontoxic M. aeruginosa FACHB 469, and the green microalga Chlamydomonas microsphaera FACHB 52. In monocultures, the growth of all three strains was inhibited by UVB. In mixed cultures, enhanced UVB radiation resulted in decreased percentages of the two M. aeruginosa strains (19%-22% decrease on d 12 of the competition experiment). UVB radiation resulted in increased contents of chlorophyll a, b, and carotenoids (CAR) in C. microsphaera, and decreased contents of allophycocyanin (APC) or phycocyanin in the two Microcystis strains. All three strains showed increased levels of UVabsorbing compounds and intracellular reactive oxygen species under 0.372 W . m(-2) UVB radiation, and decreased light compensation points, dark respiratory rates, and maximal quantum efficiency of PSII. After a 20 h recovery, the photosynthetic oxygen evolution of C. microsphaera was restored to its maximum value, but that of Microcystis strains continued to decrease. Nonphotochemical quenching was increased by UVB radiation in C. microsphaera, but was unaffected in the two M. aeruginosa strains. Our results indicated that C. microsphaera has a competitive advantage relative to Microcystis during exposure to UVB irradiation. PMID- 27008519 TI - Classification of crucigenoid algae: phylogenetic position of the reinstated genus Lemmermannia, Tetrastrum spp. Crucigenia tetrapedia, and C. lauterbornii (Trebouxiophyceae, Chlorophyta)(1). AB - The subfamily Crucigenioideae was traditionally classified within the well characterized family Scenedesmaceae (Chlorophyceae). Several morpho-logical revisions and questionable taxonomic changes hampered the correct classification of crucigenoid species resulting in a high number of synonymous genera. We used a molecular approach to determine the phylogenetic position of several Tetrastrum and Crucigenia species. The molecular results were correlated with morphological and ontogenetic characters. Phylogenetic analyses of the SSU rDNA gene resolved the position of Tetrastrum heteracanthum and T. staurogeniaeforme as a new lineage within the Oocystis clade of the Trebouxiophyceae. Crucigenia tetrapedia, T. triangulare, T. punctatum, and T. komarekii were shown to be closely related to Botryococcus (Trebouxiophyceae) and were transferred to Lemmer-mannia. Crucigenia lauterbornii was not closely related to the other Crucigenia strains, but was recovered within the Chlorella clade of the Trebouxiophyceae. PMID- 27008520 TI - Chronological transition of mitochondrial morphology in Chlamydomonas reinhardtii (Chlorophyceae) poststationary phase growth(1). AB - In Chlamydomonas reinhardtii P. A. Dangeard, mitochondrial morphology has been observed during asexual cell division cycle, gamete and zygote formation, zygote maturation, and meiotic stages. However, the chronological transition of mitochondrial morphology after the stationary phase of vegetative growth, defined as the poststationary phase, remains unknown. Here, we examined the mitochondrial morphology in cells cultured for 4 months on agar plates to study mitochondrial dynamics in the poststationary phase. Fluorescence microscopy showed that the intricate thread-like structure of mitochondria gradually changed into a granular structure via fragmentation after the stationary phase in cultures of about 1 week of age. The number of mitochondrial nucleoids decreased from about 30 per cell at 1 week to about five per cell after 4 months of culture. The mitochondrial oxygen consumption decreased exponentially, but the mitochondria retained their membrane potential. The total quantity of mitochondrial DNA (mtDNA) of cells at 4 months decreased to 20% of that at 1 week. However, the mitochondrial genomic DNA length was unchanged, as intermediate lengths were not detected. In cells in which the total mtDNA amount was reduced artificially to 16% after treatment with 5-fluoro-2-deoxyuridine (FdUrd) for 1 week, the mitochondria remained as thread-like structures. The oxygen consumption rate of these cells corresponded to that of untreated cells at 1 week of culture. This suggests that a decrease in mtDNA does not directly induce the fragmentation of mitochondria. The results suggest that during the late poststationary phase, mitochondria converge to a minimum unit of a granular structure with a mitochondrial nucleoid. PMID- 27008521 TI - The photobiology of Heterosigma akashiwo. Photoacclimation, diurnal periodicity, and its ability to rapidly exploit exposure to high light. AB - Periodic and seasonal exposure to high light is a common occurrence for many near shore and estuarine phytoplankton. Rapid acclimatization to shifts in light may provide an axis by which some species of phytoplankton can outcompete other microalgae. Patterns of photoacclimation and photosynthetic capacity in the raphidophyte Heterosigma akashiwo (Hada) Hada ex Hara et Chihara isolated from the mid-Atlantic of the United States were followed in continuous cultures at low and high-light intensities, followed by reciprocal shifts to the opposite light level. The maximum quantum yield (Fv /Fm ) as well as the photosynthetic cross section (sigmaPSII ) of photosystem II was higher in high-light cultures compared to low-light cultures. Significant diurnal variability in photochemistry and photoprotection was noted at both light levels, and high-light-acclimated cultures displayed greater variability in photoprotective pathways. When shifted from low to high light, there was only a slight and temporary decline in maximum quantum yield, while cell specific growth more than doubled within 24 h. Rapid acclimation to high light was facilitated by short-term photoprotection (nonphotochemical quenching), reduced PSII reaction center connectivity, and electron transport. Short-term increases in de-epoxidated xanthophyll pigments contributed to nonphotochemical protection, but lagged behind initial increases in nonphotochemical quenching and were not the primary pathway of photoprotection in this alga. By 48 h, photochemistry of cultures shifted from low to high light resembled long-term high-light-acclimated cultures. This isolate of H. akashiwo appears well poised to exploit rapid shifts in light by using unique cellular adjustments in light harvesting and photochemistry. PMID- 27008522 TI - Cadmium decontamination and reversal potential of teratological forms of the diatom Planothidium frequentissimum (Bacillariophyceae) after experimental contamination. AB - While the induction of teratology by cadmium (Cd) on diatoms is already known, reversal kinetics are not well documented. This study aims to understand the viability of diatoms exhibiting teratological frustules and their reproduction capacities within a Cd-impacted population to predict their return to normal diatom forms. We worked on a frequently encountered species in French hydrosystems: Planothidium frequentissimum (Lange-Bertalot) Round & L. Bukhtiyarova. First, a 21-d contamination phase highlighted increasing inductionof different teratological types in response to two levels of Cd contamination: 20 and 100 MUg . L(-1) . The deformity counting indicated that Cd firstly generated striae and mixed teratologies, then affected the central area and the valves. Second, a 28-d decontamination phase demonstrated the Cd depuration capacity of Planothidium frequentissimum. Cd half-lives appeared relatively low, ~6 d for the 100 MUg . L(-1) condition. Moreover, the decontamination phase showed a decrease in teratology abundances, but a still incomplete recovery after 28 d. Deformations of the striae appeared to be the most sustainable phenotype since they were still significantly higher than in reference cultures at the end of the decontamination phase for both Cd cultures. PMID- 27008523 TI - Cell cycle implication on nitrogen acquisition and synchronization in Thalassiosira weissflogii (Bacillariophyceae). AB - The Michaelis-Menten model of nitrogen (N) acquisition, originally used to represent the effect of nutrient concentration on the phytoplankton uptake rate, is inadequate when other factors show temporal variations. Literature generally links diurnal oscillations of N acquisition to a response of the physiological status of microalgae to photon flux density (PFD) and substrate availability. This work describes how the cell cycle also constitutes a significant determinant of N acquisition and, when appropriate, assesses the impact of this property at the macroscopic level. For this purpose, we carried out continuous culture experiments with the diatom Thalassiosira weissflogii (Grunow) G. Fryxell & Hasle exposed to various conditions of light and N supply. The results revealed that a decrease in N acquisition occurred when a significant proportion of the population was in mitosis. This observation suggests that N acquisition is incompatible with mitosis and therefore that its acquisition rate is not constant during the cell cycle. In addition, environmental conditions, such as light and nutrient supply disrupt the cell cycle at the level of the individual cell, which impacts synchrony of the population. PMID- 27008524 TI - Quantum requirements for growth and fatty acid biosynthesis in the marine diatom Phaeodactylum tricornutum (Bacillariophyceae) in nitrogen replete and limited conditions. AB - We determined the quantum requirements for growth (1/phiMU ) and fatty acid (FA) biosynthesis (1/phiFA ) in the marine diatom, Phaeodactylum tricornutum, grown in nutrient replete conditions with nitrate or ammonium as nitrogen sources, and under nitrogen limitation, achieved by transferring cells into nitrogen free medium or by inhibiting nitrate assimilation with tungstate. A treatment in which tungstate was supplemented to cells grown with ammonium was also included. In nutrient replete conditions, cells grew exponentially and possessed virtually identical 1/phiMU of 40-44 mol photons . mol C(-1) . In parallel, 1/phiFA varied between 380 and 409 mol photons . mol C(-1) in the presence of nitrate, but declined to 348 mol photons . mol C(-1) with ammonium and to 250 mol photons . mol C(-1) with ammonium plus tungstate, indicating an increase in the efficiency of FA biosynthesis relative to cells grown on nitrate of 8% and 35%, respectively. While the molecular mechanism for this effect remains poorly understood, the results unambiguously reveal that cells grown on ammonium are able to direct more reductant to lipids. This analysis suggests that when cells are grown with a reduced nitrogen source, fatty acid biosynthesis can effectively become a sink for excess absorbed light, compensating for the absence of energetically demanding nitrate assimilation reactions. Our data further suggest that optimal lipid production efficiency is achieved when cells are in exponential growth, when nitrate assimilation is inhibited, and ammonium is the sole nitrogen source. PMID- 27008525 TI - Conditional senescence in Chlamydomonas reinhardtii (Chlorophyceae). AB - The mechanisms of microalgal senescence may play an important role in nutrient recycling and enhanced survival. However, the aging physiology of microalgae is an understudied phenomenon. To investigate the patterns of conditional senescence in Chlamydomonas reinhardtii P. A. Dangeard, we used a cell wall-less strain, transformed with a reporter gene to infer changes in photosynthetic gene expression. We examined plastid ultrastructure, photosynthetic function, and photoprotective mechanisms during aging in batch cultures. LHCII transcription levels decreased before the population entered stationary phase, and the characteristic transcriptional light-shift response was lost. A decline in photosynthetic proteins with a concomitant increase in the photoprotective protein, LHCSR, was observed over time. However, nonphotochemical quenching remained stable during growth and stationary phase, and then declined as alternative quenching mechanisms were up-regulated. Photosynthetic efficiency declined, while Fv/Fm remained stable until the death phases. As the culture progressed through stationary phase, disorganization of the chloroplast was observed along with an increase in cytoplasmic oil bodies. We also observed a partial recovery of function and proteins during the final death phase, and attribute this to the release of nutrients into the medium from cell lysis and/or active secretion while cells were senescing. Allowing open gas exchange resulted in high levels of sustained starch production and maintained maximum cell density, prolonging the stationary phase. PMID- 27008526 TI - Polyphasic evaluation of Xanthidium antilopaeum and Xanthidium cristatum (Zygnematophyceae, Streptophyta) species complex. AB - We investigated twenty-six strains of Xanthidium antilopaeum Kutz. and seven strains of X. cristatum Ralfs isolated from various European localities or obtained from public culture collections. A combination of molecular, geometric morphometric, and morphological data were used to reveal the patterns of the phylogenetic and morphological differentiation of these taxonomically very compli cated desmid taxa. The molecular data based on trnG(ucc) and ITS rDNA sequences illustrated the monophyly of both the complexes, which indicated that their traditional morphology-based discriminative criteria, such as the different number of spines, may generally continue to be considered relevant. The single exception was X. antilopaeum var. basiornatum B. Eichler et Raciborski, which was positioned outside the X. antilopaeum/cristatum clade. The independent status of this taxon was also confirmed on the basis of the geometric morphometric data, so that we concluded that it probably represents a separate species. Within X. cristatum complex, the traditional varieties X. cristatum var. cristatum Ralfs, X. cristatum var. uncinatum Ralfs, and X. cristatum var. scrobiculatum Scott et Gronblad turned out to be separate taxa. Conversely, X. cristatum var. bituberculatum Lowe lacked any taxonomical value. Our data on X. antilopaeum illustrated extensive phylogenetic as well as phenotypic variability within this species complex. However, our data did not result in any unambiguous pattern that would allow sound taxonomic classification. Finally, we also found out that the morphologically peculiar Staurastrum tumidum Ralfs belongs to the genus Xanthidium based on the combined rbcL + cox III data set. Consequently, this species was formally transferred to this genus. PMID- 27008527 TI - Substrate supply for calcite precipitation in Emiliania huxleyi: assessment of different model approaches. AB - Over the last four decades, different hypotheses of Ca(2+) and dissolved inorganic carbon transport to the intracellular site of calcite precipitation have been put forth for Emiliania huxleyi (Lohmann) Hay & Mohler. The objective of this study was to assess these hypotheses by means of mathematical models. It is shown that a vesicle-based Ca(2+) transport would require very high intravesicular Ca(2+) concentrations, high vesicle fusion frequencies as well as a fast membrane recycling inside the cell. Furthermore, a kinetic model for the calcification compartment is presented that describes the internal chemical environment in terms of carbonate chemistry including calcite precipitation. Substrates for calcite precipitation are transported with different stoichiometries across the compartment membrane. As a result, the carbonate chemistry inside the compartment changes and hence influences the calcification rate. Moreover, the effect of carbonic anhydrase (CA) activity within the compartment is analyzed. One very promising model version is based on a Ca(2+) /H(+) antiport, CO2 diffusion, and a CA inside the calcification compartment. Another promising model version is based on an import of Ca(2+) and HCO3 (-) and an export of H(+) . PMID- 27008528 TI - Strain variability in fatty acid composition of Chattonella marina (Raphidophyceae) and its relation to differing ichthyotoxicity toward rainbow trout gill cells. AB - Lipid profiles of three strains (Mexico, Australia, Japan) of Chattonella marina (Subrahmanyan) Hara et Chihara were studied under defined growth (phosphate, light, and growth phase) and harvest (intact and ruptured cells) conditions. Triacylglycerol levels were always <2%, sterols <7%, free fatty acids varied between 2 and 33%, and polar lipids were the most abundant lipid class (>51% of total lipids). The major fatty acids in C. marina were palmitic (16:0), eicosapentaenoic (EPA, 20:5omega3), octadecatetraenoic (18:4omega3), myristic (14:0), and palmitoleic (16:1omega7c) acids. Higher levels of EPA were found in ruptured cells (21.4-29.4%) compared to intact cells (8.5-25.3%). In general, Japanese N-118 C. marina was the highest producer of EPA (14.3-29.4%), and Mexican CMCV-1 the lowest producer (7.9-27.1%). Algal cultures, free fatty acids from C. marina, and the two aldehydes 2E,4E-decadienal and 2E,4E-heptadienal (suspected fatty acid-derived products) were tested against the rainbow trout fish gill cell line RTgill-W1. The configuration of fatty acids plays an important role in ichthyotoxicity. Free fatty acid fractions, obtained by base saponification of total lipids from C. marina showed a potent toxicity toward gill cells (median lethal concentration, LC50 (at 1 h) of 0.44 MUg . mL(-1) in light conditions, with a complete loss of viability at >3.2 MUg . mL(-1) ). Live cultures of Mexican C. marina were less toxic than Japanese and Australian strains. This difference could be related to differing EPA content, superoxide anion production, and cell fragility. The aldehydes 2E,4E-decadienal and 2E,4E heptadienal also showed high impact on gill cell viability, with LC50 (at 1 h) of 0.34 and 0.36 MUg . mL(-1) , respectively. Superoxide anion production was highest in Australian strain CMPL01, followed by Japanese N-118 and Mexican CMCV 1 strains. Ruptured cells showed higher production of superoxide anion compared to intact cells (e.g., 19 vs. 9.5 pmol . cell(-1) . hr(-1) for CMPL01, respectively). Our results indicate that C. marina is more ichthyotoxic after cell disruption and when switching from dark to light conditions, possibly associated with a higher production of superoxide anion and EPA, which may be quickly oxidized to produce more toxic derivates, such as aldehydes. PMID- 27008529 TI - NESARC Findings on Increased Prevalence of Marijuana Use Disorders-Reply: Consistent With Other Sources of Information. PMID- 27008530 TI - Anti-apoptosis in porcine respiratory and reproductive syndrome virus. PMID- 27008531 TI - Declining Trend of Hepatitis A Seroepidemiology in Association with Improved Public Health and Economic Status of Thailand. AB - Hepatitis A virus (HAV) is transmitted via the fecal-oral route from contaminated food or water. As part of the most recent survey of viral hepatitis burden in Thailand, we analyzed the current seroprevalence of HAV in the country and compared with data dating back to 1971. From March to October, 2014, a total of 4,260 individuals between one month and 71 years of age from different geographical regions (North = 961; Central = 1,125; Northeast = 1,109; South = 1,065) were screened for anti-HAV IgG antibody using an automated chemiluminescent microparticle immunoassay. Overall, 34.53% (1,471/4,260) possessed anti-HAV IgG antibody, and the age-standardized seroprevalence was 48.6%. Seroprevalence rates were 27.3% (North), 30.8% (Central), 33.8% (Northeast) and 45.8% (South) and were markedly lower than in the past studies especially among younger age groups. The overall trend showed an increase in the age by which 50% of the population were anti-HAV IgG antibody: 4.48 years (1971 1972), 6 (1976), 12.49 (1990), 36.02 (2004) and 42.03 (2014).This suggests that Thailand is transitioning from low to very low HAV endemicity. Lower prevalence of HAV correlated with improved healthcare system as measured by decreased infant mortality rate and improved national economy based on increased GDP per capita. The aging HAV immuno-naive population may be rendered susceptible to potential HAV outbreaks similar to those in industrialized countries and may benefit from targeted vaccination of high-risk groups. PMID- 27008532 TI - Effect of Perceived Politics and Perceived Support on Bullying and Emotional Exhaustion: The Moderating Role of Type A Personality. AB - Recognizing that bullying can occur in varying degrees of severity, the current study suggest the importance of individual traits in individual perceptions of being targets of bullying and ensuing emotional exhaustion. The present study extends the work environment hypothesis and trait activation theory by a joint investigation of the mediating role of (a) workplace bullying in linking perceived organization politics and perceived organization support with emotional exhaustion and (b) the moderating role of Type A behavioral pattern in influencing the mediation. Using a field sample of 262 employees working in different organizations of Pakistan, this study tested a moderated mediation model. Results were consistent with the hypothesized model, in that workplace bullying mediated the relationship of perceived organization politics and perceived organization support with emotional exhaustion. Type A behavior moderated the perceived politics-bullying, perceived support-bullying, and bullying-emotional exhaustion relationships. The mediation of bullying varied with levels of Type A behavior in these relationships. PMID- 27008537 TI - GaAs Core/SrTiO3 Shell Nanowires Grown by Molecular Beam Epitaxy. AB - We have studied the growth of a SrTiO3 shell on self-catalyzed GaAs nanowires grown by vapor-liquid-solid assisted molecular beam epitaxy on Si(111) substrates. To control the growth of the SrTiO3 shell, the GaAs nanowires were protected using an arsenic capping/decapping procedure in order to prevent uncontrolled oxidation and/or contamination of the nanowire facets. Reflection high energy electron diffraction, scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy were performed to determine the structural, chemical, and morphological properties of the heterostructured nanowires. Using adapted oxide growth conditions, it is shown that most of the perovskite structure SrTiO3 shell appears to be oriented with respect to the GaAs lattice. These results are promising for achieving one dimensional epitaxial semiconductor core/functional oxide shell nanostructures. PMID- 27008536 TI - A Meta-Analysis of the Metabolic Syndrome Prevalence in the Global HIV-Infected Population. AB - BACKGROUND: Cardio-metabolic risk factors are of increasing concern in HIV infected individuals, particularly with the advent of antiretroviral therapy (ART) and the subsequent rise in longevity. However, the prevalence of cardio metabolic abnormalities in this population and the differential contribution, if any, of HIV specific factors to their distribution, are poorly understood. Therefore, we conducted a systematic review and meta-analysis to estimate the global prevalence of metabolic syndrome (MS) in HIV-infected populations, its variation by the different diagnostic criteria, severity of HIV infection, ART used and other major predictive characteristics. METHODS: We performed a comprehensive search on major databases for original research articles published between 1998 and 2015. The pooled overall prevalence as well as by specific groups and subgroups were computed using random effects models. RESULTS: A total of 65 studies across five continents comprising 55094 HIV-infected participants aged 17-73 years (median age 41 years) were included in the final meta-analysis. The overall prevalence of MS according to the following criteria were: ATPIII 2001:16.7% (95%CI: 14.6-18.8), IDF-2005: 18% (95%CI: 14.0-22.4), ATPIII-2004 2005: 24.6% (95%CI: 20.6-28.8), Modified ATPIII-2005: 27.9% (95%CI: 6.7-56.5), JIS-2009: 29.6% (95%CI: 22.9-36.8), and EGIR: 31.3% (95%CI: 26.8-36.0). By some MS criteria, the prevalence was significantly higher in women than in men (IDF 2005: 23.2% vs. 13.4, p = 0.030), in ART compared to non-ART users (ATPIII-2001: 18.4% vs. 11.8%, p = 0.001), and varied significantly by participant age, duration of HIV diagnosis, severity of infection, non-nucleoside reverse transcriptase inhibitors (NNRTIs) use and date of study publication. Across criteria, there were significant differences in MS prevalence by sub-groups such as in men, the Americas, older publications, regional studies, younger adults, smokers, ART-naive participants, NNRTIs users, participants with shorter duration of diagnosed infection and across the spectrum of HIV severity. Substantial heterogeneities across and within criteria were not fully explained by major study characteristics, while evidence of publication bias was marginal. CONCLUSIONS: The similar range of MS prevalence in the HIV-infected and general populations highlights the common drivers of this condition. Thus, cardio metabolic assessments need to be routinely included in the holistic management of the HIV-infected individual. Management strategies recommended for MS in the general population will likely provide similar benefits in the HIV-infected. PMID- 27008538 TI - A New Species of Cleisostoma (Orchidaceae) from the Hon Ba Nature Reserve in Vietnam: A Multidisciplinary Assessment. AB - A new species, Cleisostoma yersinii J. Ponert & Vuong, is described and illustrated based on the material collected in the Hon Ba Nature Reserve in southern Vietnam. In addition to conventional (macro)morphological examination we comparatively investigated root and leaf anatomy (using light and fluorescent microscopy), assessed nectar characteristics (using HPLC analysis), determined nuclear genome size (using DNA flow cytometry) and reconstructed phylogenetic relationships (using nrITS sequences). Cleisostoma yersinii differs from its putative closest relative C. birmanicum in wider and shorter leaves, larger flowers, distinct lip with S-shaped tip of the mid-lobe, and a shallow spur with two large nectar sacks separated by prominent calli and septum. Nectar is sucrose dominant and very rich in sugars. Stomata are developed on both sides of the leaf and have prominent hyperstomatal chambers and substomatal cavities. Roots with well-developed exodermis and tracheoidal idioblasts are covered by a two-layer Vanda-type velamen. Chloroplasts occur not only in the cortex but are also abundant in the stele. Mean 1C-value was estimated to 2.57 pg DNA. An updated identification key is provided for SE Asian sections and all Vietnamese species of Cleisostoma. PMID- 27008540 TI - Food Insecurity in Patients with High Hospital Utilization. AB - Having access to adequate and appropriate food is a major population health issue. This study investigated food insecurity in patients with high rates of inpatient hospitalization ("super-utilizers"). Forty adults with >=3 hospital inpatient admissions within a 12-month period were interviewed in an urban hospital in Philadelphia, Pennsylvania, between March 2015 and May 2015. Inpatient admission history was obtained from hospital billing data. The majority had >=5 hospitalizations in the past 12 months and >=6 chronic conditions. Using the USDA definition of food insecurity, 30% (95% CI, 17% to 47%) were food insecure and 25% (95% CI, 13% to 41%) were marginally food secure. Forty percent responded that, in the past 30 days, they worried that their food would run out; 35% that their food would not last; 17.5% that they did not eat for a full day; and 10% that they were hungry but did not eat some or all of the time. Additionally, 75% were unable to shop for food on their own and 58% were unable to prepare their own food. More than half reported using food pantries or other community food resources. The impact of unmet food needs on hospital super utilization warrants further investigation. Interventions that educate and connect patients with unmet food needs to community resources can help engage patients in their own health and well-being. Communication with patients about whether they have enough nutritionally appropriate food for their health conditions is an important starting point. PMID- 27008541 TI - Coarse-Grained Theory of Biological Charge Transfer with Spatially and Temporally Correlated Noise. AB - System-environment interactions are essential in determining charge-transfer (CT) rates and mechanisms. We developed a computationally accessible method, suitable to simulate CT in flexible molecules (i.e., DNA) with hundreds of sites, where the system-environment interactions are explicitly treated with numerical noise modeling of time-dependent site energies and couplings. The properties of the noise are tunable, providing us a flexible tool to investigate the detailed effects of correlated thermal fluctuations on CT mechanisms. The noise is parametrizable by molecular simulation and quantum calculation results of specific molecular systems, giving us better molecular resolution in simulating the system-environment interactions than sampling fluctuations from generic spectral density functions. The spatially correlated thermal fluctuations among different sites are naturally built-in in our method but are not readily incorporated using approximate spectral densities. Our method has quantitative accuracy in systems with small redox potential differences (